KR101436792B1 - A Composition containing Naphthoquinone for Controlling Harmful Algae - Google Patents
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Abstract
본 발명은 특정 나프토퀴논(Naphthoquinone) 화합물의 유해조류 제어 용도에 관한 것으로, 특정 나프토퀴논(Naphthoquinone) 화합물 또는 그의 염을 유효성분으로 함유하는 유해조류 제어용 조성물 및 이를 이용한 유해 조류의 제어(방제)방법에 관한 것으로, 본 발명의 혼합조성물은 녹조, 적조 등의 유해 조류에 대해 선택적인 생육억제효과를 나타내므로, 본 발명은 환경 친화적이면서 효능이 우수한 유해 조류 방제제로서 유용하게 활용될 수 있다.The present invention relates to the use of specific naphthoquinone compounds for the control of harmful algae, and relates to a composition for controlling harmful algae containing a specific naphthoquinone compound or a salt thereof as an active ingredient and to control (control ) Method. Since the mixed composition of the present invention exhibits a selective growth inhibitory effect against harmful algae such as green tide, red tide, etc., the present invention can be effectively utilized as a harmful algae controlling agent which is environmentally friendly and excellent in efficacy .
Description
본 발명은 특정 나프토퀴논(Naphthoquinone) 화합물 또는 그의 염을 유효성분으로 함유하는 녹조 제어용 조성물에 관한 것으로, 보다 구체적으로는, 특정 치환기를 가지는 나프토퀴논 화합물이 담수산 유해조류 광합성 체계(photosynthetic system)의 Q-사이트에 작용하여 광합성을 선택적으로 저해함으로써 담수산 유해조류(녹조)에 살조 효과를 가지는, 특정 나프토퀴논(naphthoquinone) 화합물의 용도에 관한 것이다.
The present invention relates to a composition for controlling an algae containing a specific naphthoquinone compound or a salt thereof as an active ingredient, and more particularly, to a composition for controlling algae containing a specific naphthoquinone compound or a salt thereof as a photosensitizing system (Q-site) to selectively inhibit photosynthesis, thereby having a killing effect on harmful algae (green algae) of freshwater fish.
유해 조류의 대발생(HAB, Harmful Algal Blooming)은 이들의 생육 서식지에 따라 산업적으로 다양한 문제를 일으키고 있다. 호수, 하천, 저수지, 양어장 등지에서의 유해조류의 대발생은, 1) 수생생물의 폐사를 일으키고 (Duke 등, Weed Sci. 50: 138-151, 2002); 2) 이취미(off-flavor) 물질을 발생시켜 음용수 및 양식어류의 육질을 떨어뜨리는데, 예를 들면, 유해 조류인 오실라토리아 페로나타(Oscillatoria perornata)의 서식지에서는 물고기에 흙냄새(off-flavor)가 나게 되며(Duke 등, Weed Sci. 50: 138-151, 2002); 3) 사람 및 동물에 유해한 독소가 생성되는데, 예를 들어, 마이크로시스티스(Microcystis) 속, 노듈라리아(Nodularia) 속, 아나베나(Anabaena) 속, 아파니조메논(Aphanizomenon)속 등의 일부 조류는 각각 사람 및 동물에 유해한 독소인 마이크로시스틴(microcystins), 노듈라린(nodularin), 아나톡신(anatoxin) 및 삭시톡신(saxitoxin)을 생산한다고 알려져 있고(Haider 등, Chemosphere 52:1-21, 2003); 4) 물의 착색 및 이상발포(scum) 형성 등으로 불쾌감을 유발하고 여가 및 산업 활동을 저해하며; 5) 상수처리과정 중의 여과지 폐쇄 및 응집 침전 저해 등으로 인해 염소의 과다처리가 필요하므로 경제적 손실을 야기한다.HAB (Harmful Algal Blooming) causes various industrial problems depending on their habitat. The major outbreaks of harmful algae in lakes, rivers, reservoirs, fish farms, etc., have caused 1) the death of aquatic organisms (Duke et al., Weed Sci. 50: 138-151, 2002); 2) This off-flavor substance causes the degradation of the quality of drinking water and aquaculture. For example, in the habitat of the harmful algae Oscillatoria perornata, off- flavor) (Duke et al., Weed Sci. 50: 138-151, 2002); 3) Toxins harmful to humans and animals are produced, for example, some birds such as Microcystis, Nodularia, Anabaena, Aphanizomenon, Are known to produce microcystins, nodularins, anatoxins and saxitoxins, which are harmful to humans and animals, respectively (Haider et al., Chemosphere 52: 1-21, 2003); 4) causing discomfort by coloring of water and formation of abnormal scum, and inhibiting leisure and industrial activities; 5) It causes economic loss because it requires excessive treatment of chlorine due to clogging of filter paper and inhibition of coagulation sedimentation during the process of water treatment.
한편, 담수직 파답에서는 조류의 대발생이 괴불 형성을 유도하여 입모율을 현저히 감소시키기도 하고, 토양온도를 저하시켜 작물의 생산성을 저감시키기도 한다. 골프장 페어웨이에서는 토양조류의 대발생으로 잔디가 고사하는 경우도 많다. 또한, 건축 및 산업시설 현장에서는 유해조류가 수질오염, 기계의 오작동, 노후화 촉진, 미관 손상 등 다양한 피해를 유발시키기도 한다.On the other hand, in the vertical ripening, algae larvae induce nodule formation, which significantly reduces the seeding rate and lowers the soil temperature, thereby reducing crop productivity. In the golf fairway, there are many cases where the grass is damaged due to the occurrence of the soil algae. In addition, harmful algae can cause various damages such as water pollution, malfunction of machinery, promotion of aging, aesthetic damage, etc. in the field of construction and industrial facilities.
따라서 유해조류 원인생물에 의한 현상을 제거 또는 완화시키기 위한 기술들이 개발되었는데, 지금까지 알려진 기술들로는 화학약품 살포법, 초음파 및 오존처리법, 해면회수 및 침강법, 황토살포법 등이 있다.Therefore, techniques for eliminating or alleviating the phenomena caused by harmful algae have been developed. Examples of techniques known so far include a chemical spraying method, an ultrasonic ozone treatment method, a sea surface recovery and sedimentation method, and a loess spraying method.
부영양성 호수 및 하천에서 유해조류 대발생으로 증가된 수중 내 오염물질 (자체생성유기물: 녹조생물)을 제어하는 것은 수자원 문제해결의 가장 핵심적인 부분이며, 적용될 기술 역시 경제성이 높고 생태계 혼란이 가장 적은 친환경적인 기술이어야 한다.Control of pollutants in water (self-generated organisms: green algae), which is caused by harmful algal blooms in eutrophic lakes and rivers, is the most critical part of water resource resolution and the technology to be applied is also economical and ecosystem confusion is the least It should be eco-friendly technology.
그러나 화학약품 살포법은 황산구리(CuSO4), 이산화염소(ClO2), 시마진(Simazine) 등을 살포하는 방법으로서 과거부터 이용되어 왔는데, 그 중 비용이 가장 저렴하여 널리 이용되는 황산구리는 적조원인 생물 외에 다른 해양생물에까지 영향을 끼쳐 수중의 다른 생물에 대한 독성 및 부식의 측면에서 문제를 일으킬 수 있으며, 또한 일시적 효과만 나타내기 때문에 반복 사용해야 하고, 적조 발생시 수반되는 높은 알칼리성 환경 조건하에서는 황산구리가 불안정해지기 때문에 많은 양을 처리하여야 하므로 비경제적이라는 단점이 있다. However, the chemical spraying method has been used since the past as a method of spraying copper sulfate (CuSO4), chlorine dioxide (ClO2), simazine (Simazine), among which copper sulfate, which is the most inexpensive, It may cause problems in terms of toxicity and corrosion to other organisms in the water due to its influence on other marine life, and it should be repeatedly used because it shows only transient effect, and it is necessary to use it repeatedly under high alkaline environment conditions accompanied with the occurrence of red tide, Therefore, it is disadvantageous in that it is not economical to process a large amount.
초음파 처리법은 초음파(160~400kHz)로 적조원인생물의 세포를 파괴하는 방법이고, 오존처리법은 적조 발생 수역에 고압의 오존을 투입하여 적조로 인한 독성을 중화시키는 방법이나, 두 방법 모두 실용화단계에는 아직 이르지 못하고 있는 실정이다. The ultrasonic treatment method is a method of destroying the cells of the organism causing the red tide with ultrasonic waves (160 to 400 kHz), and the ozone treatment method is a method of neutralizing the toxicity due to the red tide by injecting high pressure ozone into the red tide occurrence water area. It has not come yet.
해면회수 및 침강법은 원심분리기, 응집본조, 혼합조 및 가압부상조로 구성된 가압부상분리장치를 이용하여 기포를 발생시켜 적조 생물을 흡착, 부상시키고 해표면에서 회수하는 방법이며, 황토살포법은 황토를 해수 중에 살포하여 적조생물을 흡착 침강시키고, 황토속의 알루미늄 이온이 적조원인 생물의 세포를 파괴시키는 성질을 이용한 방법이다. 그러나 해수 중에 황토를 살포하면 부유물질이 증가되어 어류 양식장과 저층에 정착생물이 살고 있는 어장에서는 어류 아가미 폐쇄로 호흡 장애 등 생물에 영향을 미칠 수 있는 문제점이 있다. The sea surface recovery and sedimentation method is a method in which bubbles are generated by using a pressurized floating separator composed of a centrifugal separator, an agglomeration basin, a mixing tank and a pressurized float tank to adsorb and float the red tide creatures and recover from the sea surface. Is sprayed in seawater to adsorb and precipitate red tide organisms, and aluminum ions in the loess destroy the cells of living organisms caused by red tide. However, when loess is sprayed in seawater, suspended matter increases in fisheries farms and fisheries where settlement creatures live in the lower layer, which can affect living things such as respiratory disorders due to fish gill closure.
그리고, 살조제 이외에도 심층폭기/강제순환, 가압부상/물리적 수거, 초음파/오존처리 등의 물리, 화학적인 방법과 녹조를 제어가능한 세균, 바이러스, 곰팡이, 원생생물, 동물플랑크톤 등을 활용하는 생물학적인 방법 등이 있고, 여타 물리, 화학적 방법은 중, 소규모 수계에서 수질개선과 유지를 위해 많이 사용되고 있다. 그러나 이 방법의 경우 적용 수계의 규모와 환경적 특징에 따라서 적용이 어려운 경우와 효과가 미미한 경우가 많이 발생하였다. 게다가 전력, 노동력, 설비, 운영비 등의 부가적인 비용이 발생하는 문제점이 있다. 생물학적 방법의 경우에는 현재까지 실제 현장에서 그 효과를 인정받지 못하였으며, 외생종의 현장투여로 인한 생태계 교란과 현장에 투여하기 앞서 필요한 배양시설과 유지관리 비용이 발생하는 등의 문제점이 대두되었다. In addition to phytochemicals, physical and chemical methods such as deep aeration / forced circulation, pressurized flotation / physical collection, ultrasonic / ozone treatment, and biologic methods using bacteria, viruses, fungi, protozoa, zooplankton, And other physical and chemical methods are widely used for improving and maintaining water quality in medium and small scale water systems. However, in this method, it was difficult to apply the method and the effect was insignificant depending on the scale and environmental characteristics of the applied water system. In addition, there is a problem that additional costs such as power, labor, equipment, and operating expenses are incurred. In the case of biological methods, the effect has not been recognized in actual field until now, and problems such as disturbance of ecosystem caused by field application of exogenous species and necessary culture facility and maintenance cost have arisen before administration on site.
일례로 정부는 4대강 수계 물관리 종합대책의 일환으로 1993억원을 들여 4대 강에 하천정화시설, 가압부상시설, 수초재배섬, 호소수질조사선, 수질정화습지, 생태보 (어도), 초기우수처리시설 (stormfilter 등) 등 기존의 녹조제어기술을 사용하여 99년부터 2005년까지 녹조방지사업을 추진하였으나 4대강 녹조방지사업이 큰 실효를 못거두고 있는 것으로 드러났다. For example, the government has invested KRW 13.5 billion as a part of comprehensive measures for water management in the four rivers, and it is expected that the four major rivers will be equipped with river purification facilities, pressurized floodplain, aquatic cultivation islands, lake water quality survey, water quality purification wetlands, And the treatment facilities (stormfilter, etc.) using the existing green algae control technology from 1999 to 2005 to promote the algae prevention business, but the four major rivers, the anti-algae project has proven to be a great inefficiency.
즉, 현재까지 국내에선 연중 수시로 발생하는 녹조를 효과적으로 제어할 수 있는 방법이 전무한 형편이다.
In other words, there is no way to effectively control green algae that occur from time to time in Korea until now.
이에 본 발명자들은 녹조를 유발시키는 담수산 유해조류의 생성 및 증식을 억제할 수 있는 새로운 조성물을 개발하던 중, 나프토퀴논 유도체 화합물들이 담수산 유해조류의 광합성 체계(photosynthetic system)의 Q-사이트에 작용하여 광합성을 선택적으로 저해함으로써 담수산 유해조류에 대하여 우수한 살조 효과가 있음을 확인하고, 본 발명을 완성하였다.
Accordingly, the present inventors have developed a novel composition capable of inhibiting the production and proliferation of harmful algae causing green algae, and have found that naphthoquinone derivative compounds are effective in the Q-site of photosynthetic system of freshwater marine algae And selectively inhibited photosynthesis. Thus, the present inventors have confirmed that the present invention has an excellent killing effect on harmful algae of freshwater fish, and completed the present invention.
본 발명은 나프토퀴논 유도체 화합물의 유해조류 제어 용도를 제공하는 것을 목적으로 한다.It is an object of the present invention to provide a naphthoquinone derivative compound for controlling harmful algae.
본 발명의 다른 목적은 나프토퀴논 유도체 화합물을 함유하는 유해조류 제어용 조성물을 제공하는 것이다.It is another object of the present invention to provide a composition for controlling harmful algae containing a naphthoquinone derivative compound.
본 발명의 또 다른 목적은 나프토퀴논 유도체 화합물을 이용하여 유해조류의 이상 증식을 제어 또는 방지하는 방법을 제공하는 것이다.
It is another object of the present invention to provide a method for controlling or preventing an abnormal growth of harmful algae using a naphthoquinone derivative compound.
상기 목적을 달성하기 위하여, 본 발명은 하기 화학식 1의 나프토퀴논(Naphthoquinone) 화합물 또는 그의 염을 유효성분으로 함유하는 유해조류 제어용 조성물을 제공한다.In order to achieve the above object, the present invention provides a composition for controlling harmful birds, comprising a naphthoquinone compound represented by the following formula (1) or a salt thereof as an active ingredient.
[화학식 1] [Chemical Formula 1]
상기 식 중, Wherein,
R1 및 R2는 각각 독립적으로 부존재하거나, H 또는 C1~C4 알킬이고,R 1 And R 2 are each independently absent or, H or C 1 ~ C 4 Alkyl,
R3는 치환 또는 비치환 , CH, NH, SH, CH2-NH, 또는 CH=N이고, R 3 is a substituted or unsubstituted , CH, NH, SH, CH2-NH, or CH = N,
R4는 부존재하거나, 수소, 치환 또는 비치환된 C1~C12 알킬, 치환 또는 비치환 (헤테로)사이클로알킬, (헤테로)사이클로알케닐 또는 (헤테로)아릴이며,R 4 is absent or is hydrogen, substituted or unsubstituted C 1 -C 12 alkyl, substituted or unsubstituted (hetero) cycloalkyl, (hetero) cycloalkenyl or (hetero)
점선은 단일결합 또는 이중결합이다.The dotted line is a single bond or a double bond.
이 때, R1 및 R2는 각각 독립적으로 부존재하거나, H 또는 CH3일 수 있고, 상기 R1과 R2가 각각 독립적으로 부존재할 경우 점선은 이중결합일 수 있다.In this case, R 1 and R 2 may be independently absent or may be H or CH 3 , and when R 1 and R 2 are not independently present, the dotted line may be a double bond.
상기 R4의 치환된 알킬은 H, O, N, S, Cl, F, OH 또는 COOH로 치환될 수 있으나, 이에 제한되지 않는다.
The substituted alkyl of R < 4 > may be substituted with H, O, N, S, Cl, F, OH or COOH, but is not limited thereto.
일 구체예로써, In one embodiment,
R1이 CH3이고, R2는 부존재, R3가 인 경우, 상기 R4는 부존재할 수 있고; R3이 CH인 경우, 상기 R3와 R4 사이에 이중결합이 형성되어 있을 수 있으며; R 1 is CH 3 , R 2 is absent, R 3 is , R < 4 > may be absent; When R 3 is CH, a double bond may be formed between R 3 and R 4 ;
상기 R1 및 R2는 각각 독립적으로 부존재하거나, H 또는 CH3이고, R3가 CH2-NH 또는 CH=N인 경우, 상기 R4는 OCH3, , , , , , 또는 로 이루어진 군중에서 선택될 수 있고,Wherein R 1 and R 2 are independently absent or are H or CH 3 , and when R 3 is CH 2 -NH or CH═N, R 4 is OCH 3 , , , , , , or , ≪ / RTI >
이 때, 상기 R5는 O 또는 S이고, 상기 R6은 Cl, SO2-CH3, OCH3, NO2, OCH2CH3, F, (CH3)p 또는 부존재하고, 상기 p는 1 또는 2이며, 상기 R7은 CH3 또는 NO2일 수 있다.Wherein R 5 is O or S and R 6 is Cl, SO 2 -CH 3 , OCH 3 , NO 2 , OCH 2 CH 3 , F, (CH 3 ) p or absent, or 2, wherein R 7 may be CH 3 or NO 2.
다른 구체예로써, R1은 OCH3, R2은 부존재, R3은 CH인 경우, 상기 R4는 OCH3, 또는 일 수 있고; In another embodiment, when R 1 is OCH 3 , R 2 is absent and R 3 is CH, R 4 is OCH 3 , or Lt; / RTI >
R1과 R2가 각각 독립적으로 부존재, H, 또는 CH3이고, 상기 R3이 S인 경우, 상기 R4는 , 또는 일 수 있다.
R 1 and R 2 are each independently absent, H, or CH 3 , and when R 3 is S, R 4 is , or Lt; / RTI >
또다른 구체예로써, R1과 R2가 각각 독립적으로 부존재, H, 또는 CH3이고, 상기 R3가 NH인 경우, 상기 R4는 이며, 이 때, 상기 R8은 치환 또는 비치환된 C1~C12 알킬, 치환 또는 비치환 (헤테로)사이클로알킬, (헤테로)사이클로알케닐 또는 (헤테로)아릴이며, 상기 n은 0 내지 11인 정수임; 또는As another specific example, when R 1 and R 2 are each independently absent, H, or CH 3 , and when R 3 is NH, R 4 is And, this time, R 8 is a substituted or unsubstituted C 1 ~ C 12 alkyl, substituted or unsubstituted (hetero) cycloalkyl, (hetero) cycloalkenyl, or (hetero) aryl, wherein n is 0 to 11, ; or
R8은 CR9 , OR10, NR11, NHR12, 및 Cl로 이루어진 군중에서 선택되며, R 8 is selected from the group consisting of CR 9 , OR 10 , NR 11 , NHR 12 , and Cl,
이 때, 상기 CR9는 CH3, , , COOH, , , , , , , , , , ,또는 이고, In this case, the CR 9 may be CH 3 , , , COOH, , , , , , , , , , ,or ego,
상기 OR10은 OH, OCH3, OCH2CH2OH,또는 이며 OR 10 is OH, OCH 3 , OCH 2 CH 2 OH, or And
상기 NR11은 , , 또는 이며,
The NR < 11 & , , or Lt;
상기 NHR12는 NHCH2CH3, NHCH2CH2OH, 또는 일 수 있다. The NHR 12 is NHCH 2 CH 3, NHCH 2 CH 2 OH, or Lt; / RTI >
이 때, 상기 R8의 치환된 C1~C12 알킬은 H, O, N, S, Cl, F, OH 또는 COOH로 치환될 수 있으나, 제한은 없다.
특히, 상기 화학식 1로 표시되는 화합물은 후술하는 [NQ01-1] 내지 [NQ49-p](이하, 'NQ"는 기재를 생략한다.)로 구성된 군에서 선택되는 화합물 또는 그의 동종체 화합물을 포함한다.At this time, the R 8 substituted C1 ~ C12 alkyl are, but may be substituted with H, O, N, S, Cl, F, OH or COOH, is unlimited.
In particular, the compound represented by
삭제delete
삭제delete
바람직하게는 01-4, 01-3, 02-4, 02-3, 03-4, 03-3, 04-4, 04-3, 05-4, 05-3, 06-3, 07-3, 07-4, 09-4, 09-3, 10-3, 11-4, 11-3, 15-4, 15-3, 16-4, 18-4, 19-4, 19-3, 21-4, 21-3, 26, 32, 35, 38, 40, 42이고, 더욱 바람직하게는 01-4, 01-3, 03-3, 04-4, 04-3, 05-4, 06-3, 09-4, 15-4, 15-3, 18-4, 22-4, 40, 47, 48 이다.Preferably 01-4, 01-3, 02-4, 02-3, 03-4, 03-3, 04-4, 04-3, 05-4, 05-3, 06-3, 07-3 , 07-4, 09-4, 09-3, 10-3, 11-4, 11-3, 15-4, 15-3, 16-4, 18-4, 19-4, 19-3, 21 4, 21-3, 26, 32, 35, 38, 40, 42, more preferably 01-4, 01-3, 03-3, 04-4, 04-3, 05-4, 3, 09-4, 15-4, 15-3, 18-4, 22-4, 40, 47,
이 때, 상기 01-4, 06-3, 40, 15-3, 02-3, 15-3, 19-4, 22-4, 40, 46, 47, 48, 49은 남조강에 대해서 살조효과를 가지고, 01-4, 02-3, 04-4, 04-3, 05-4, 09-4, 10-3, 15-4, 18-4, 22-4, 41은 규조강에 대해서 살조효과를 가지며, 22-4는 와편모조류에 살조효과를 보인다
At this time, the 01-4, 06-3, 40, 15-3, 02-3, 15-3, 19-4, 22-4, 40, 46, 47, 48, 01-4, 02-3, 04-4, 04-3, 05-4, 09-4, 10-3, 15-4, 18-4, 22-4, and 41, , And 22-4 has a keloid effect on the budworm algae
그리고, 본 발명의 상기 조성물은 담수산 유해조류의 광합성 체계의 Q-사이트에 작용하여 광합성활성을 저해함으로써 유해조류에 대해서 살조효과를 발휘한다.The composition of the present invention acts on the Q-site of the photosynthetic system of freshwater marine algae to inhibit photosynthesis activity, thereby exerting a killing effect on harmful algae.
상기 유해조류는 남조강, 규조강, 녹조강, 유글레조강, 와편모조강, 황색편모조강, 갈색편모조강 또는 홍조강 조류 등을 포함한다. The harmful algae include Namchogang, Diatomaceous River, Green River, Yugurejo River, Wrapped Imitation River, Yellow Copper Crude River, Brown Copper Crude River or Red Brick River.
예를 들어, 상기 남조강(Cyanophyceae) 조류는 마이크로시스티스(Microcystis), 아나베나(Anabaena), 아파니존메논(Aphanizomenon), 오실라토리아(Oscillatoria), 및 워로니키니아(Woronichinia) 속 조류로 이루어진 군중에서 선택되는 1종 이상일 수 있고, 바람직하게는 마이크로시스티스(Microcystis) 또는 아나베나(Anabaena) 속 조류일 수 있다.For example, the Cyanophyceae algae are composed of microcystis, Anabaena, Aphanizomenon, Oscillatoria, and Woronichinia birds. It may be at least one species selected from the crowd, preferably microcystis or anabaena species.
상기 규조강(Bacillariophyceae) 조류는 스테파노디스커스(Stephanodiscus), 사이클로텔라(Cyclotella), 사이클로스테파노스(Cyclostaphanos), 아울라코세이라(Aulacoseira), 멜로지라(Melosira), 탈라지오지라(Thalassiosira), 케토세로스(Chaetoceros) 스켈레토네마(Skeletonema), 아크난테스(Achnanthes), 아스테리오넬라(Asterionella), 아칸토세라스(Acanthoceras), 나비큘라(Navicula), 니츠취아(Nitzschia), 디플로네시스(Diploneis), 심벨라(Cymbella), 곰포네마(Gomphonema), 수리렐라(Surirella), 시네드라(Synedra), 프레즐라리아(Fragilaria), 실린드로세카(Cylindrotheca), 유캄피아(Eucampia), 코스마리움(Cosmarium), 및 타벨라리아(Tabellaria) 속 조류 등으로 이루어진 군중에서 선택되는 1종 이상일 수 있고, 바람직하게는 스테파노디스커스(Stephanodiscus), 사이클로텔라(Cyclotella), 또는 아울라코세이라(Aulacoseira)일 수 있다. The Bacillariophyceae algae may be selected from the group consisting of Stephanodiscus, Cyclotella, Cyclostaphanos, Aulacoseira, Melosira, Thalassiosira, Chaetoceros Skeletonema, Achnanthes, Asterionella, Acanthoceras, Navicula, Nitzschia, Diploneis, Cymbella, Gomphonema, Surirella, Synedra, Fragilaria, Cylindrotheca, Eucampia, Kosumerium, Crombie, The present invention relates to a microorganism belonging to the genus Escherichia, which can be one or more species selected from the group consisting of Alzheimer's disease, Alzheimer's disease, Cosmarium, and Tabellaria algae, and is preferably selected from the group consisting of Stephanodiscus, Cyclotella, .
상기 녹조강(Chlorophyceae) 조류는 클로스테리옵시스(Closteriopsis), 클로스테리움(Closterium), 하이드로테카(Hydrotheca), 스피로기라(Spirogyra), 고나토지곤(Gonatozygon), 액티나스트륨(Actinastrum), 마이크락티니움(Micractinium), 라걸헤이미어(Lagerheimia), 웨스텔라(Westella), 유도리나(Eudorina), 판도리나(Pandorina), 볼복스(Volvox), 딕티오스페리움(Dictyospaerium), 클라로코쿰(Chlorococcum), 보트리오코쿠스(Botryococcus), 스타우라스트륨(Staurastrum), 클로스테리움(Closterium), 모노라피디움(Monoraphidium), 안키스트로데스무스(Ankistrodesmus), 컬크네리엘라(Kirchneriella), 페디아스트룸(Pediastrum), 세네데스무스(Scenedesmus), 코엘라스트륨(Coelastrium), 클라미도모나스(Clamydomonas) 및 클로렐라(Chlorella) 속 조류 등으로 이루어진 군중에서 선택되는 1종 이상일 수 있다.The Chlorophyceae algae may be selected from the group consisting of Closteriopsis, Closterium, Hydrotheca, Spirogyra, Gonatozygon, Actinastrum, And may be used in conjunction with other devices such as Micractinium, Lagerheimia, Westella, Eudorina, Pandorina, Volvox, Dictyospaerium, Such as Chlorococcum, Botryococcus, Staurastrum, Closterium, Monoraphidium, Ankistrodesmus, Kirchneriella, , Pediastrum, Scenedesmus, Coelastrium, Clamydomonas, and Chlorella species, and the like. In addition, the present invention is not limited thereto.
또한, 상기 유글레나조강(Euglenophyceae) 조류는 트라켈로모나스(Trachelomonas), 파커스(Phacus), 또는 유글레나(Euglena) 속 조류 등일 수 있고, 상기 와편모조강(Dinophyceae) 조류는 페리디늄(Peridinium), 세라티움(Ceratium)속 조류 등일 수 있으며, 상기 황색편모조강(Chrysophyceae) 조류는 디노브리온(Dinobryon), 유로글레나(Uroglena), 시누라(Synura) 및 말로모나스(Mallomonas) 속 조류 등으로 이루어진 군중에서 선택되는 1종 이상일 수 있고, 상기 갈색편모조강(Cryptophyceae) 조류의 경우 크립토모나스(Cryptomonas) 속 조류 등일 수 있으며, 상기 홍조강(Phodophyceae) 조류의 경우 로도모나스(Rhodomonas)속 조류 등일 수 있다.
In addition, the Euglenophyceae algae may be Trachelomonas, Phacus, or Euglena algae, and the Dinophyceae algae may be selected from the group consisting of Peridinium, And Ceratium genus algae. The yellow Chrysophyceae algae include Dinobryon, Uroglena, Synura and Mallomonas birds, and the like. And may be at least one species selected from the group consisting of Cryptophyceae birds, Cryptomonas birds and the like, and the Phodophyceae birds may be Rhodomonas birds and the like. .
본 발명은 다른 관점에서 상기 나프토퀴논 화합물 또는 그의 염을 함유하는 조성물을 적조, 특히 녹조 등 유해조류가 번무한 지역 또는 발생징후가 관찰된 지역에 처리하여 유해조류의 제어방법을 제공한다. 이는 선박을 이용하여 국부적으로 살포하는 형태로 이루어지는 것이 일반적이다.In another aspect, the present invention provides a method for controlling harmful algae by treating a composition containing the naphthoquinone compound or a salt thereof, in an area where harmful algae such as a red tide, especially green tide, are observed or where signs of occurrence are observed. This is generally done in a form of spraying locally using a vessel.
본 발명의 화합물 또는 그의 염은 각각에 따라 최종농도가 0.2 μM ~ 100 μM 범위 내에서 적절히 사용할 수 있는데, 화합물 48, 6-3, 15-3, 47 및 40; 22-4, 4-4, 4-3, 18-4, 28 등은 바람직하게는 0.2 μM ~ 2μM가 되도록 처리하여도 유해조류의 90% 이상을 효과적으로 제어가능하다.
The compound of the present invention or a salt thereof can be suitably used in the final concentration within the range of 0.2 μM to 100 μM depending on the respective compounds 48, 6-3, 15-3, 47 and 40; 22-4, 4-4, 4-3, 18-4, 28 and the like are preferably controlled to be 0.2 [mu] M to 2 [mu] M, 90% or more of harmful algae can be effectively controlled.
본 발명에 따른 신규한, 녹조 등을 포함하는 유해조류 제어용 조성물은 연못, 저수지, 호수, 호소, 하천 또는 강 등에서 유해조류(녹조류, 남조류, 규조류, 유글레노이드류, 편모조류 및 황녹색조류)의 이상 증식으로 발생한 종만을 선택적으로 제어가능하므로 담수 또는 기수역에서 녹조 또는 적조 등의 피해를 예방하고 수질오염을 방지하는데 매우 유용하게 사용될 수 있다. 또한, 녹조 또는 적조에 대한 방오제 또는 도료의 중요한 성분으로 활용가능하다.
The novel composition for controlling harmful birds including green algae according to the present invention is useful for the control of harmful algae (green algae, algae, diatoms, yugelenoids, flagella algae, and sulfur yellow algae) in ponds, reservoirs, It is possible to selectively control the species caused by abnormal proliferation, so that it can be very useful for preventing damages such as green tide or red tide in fresh water or a wastewater and preventing water pollution. Also, it can be used as an important component of antifouling agent or paint for green tide or red tide.
도 1은 본 발명의 133종의 신규 화합물 나프토퀴논의 전체 구조를 구성하는 6가지의 기본 화학적 구조골격을 나타낸다.
도 2는 녹조종류와 발생규모에 따른 신규 화합물 나프토퀴논의 선택과 적용량을 매뉴얼 화한 결과를 나타낸 그래프이다.
도 3은 미국 EPA 기준 생태독성평가를 위한 지표조류 셀레나스트륨 카프리코너튬, 지표동물 플랑크톤 다프니아 마그나, 지표어류 제브라피쉬에 대한 가장 우수한 살조활성을 보유한 신규 화합물 나프토퀴논 3종(04-4, 06-3, 40)의 독성평가 결과를 나타낸 그래프이다.
도 4는 우수한 살조활성을 보유한 신규 화합물 나프토퀴논 04-4, 06-3 및 40의 현장생태계 내 적용을 위한 실험구 및, 신규 화합물을 적용 전후의 결과이다.Fig. 1 shows six basic chemical structural skeletons constituting the entire structure of the 133 new compounds naftoquinone of the present invention.
FIG. 2 is a graph showing the results of manual selection and application amount of a novel compound naphtoquinone according to the kind of green alga and the occurrence scale.
FIG. 3 is a graph showing the results of the evaluation of three new compounds naphthoquinone (04-4) having the best tidal activity against the indicator algae Selenastium capricornium for evaluation of ecotoxicity based on US EPA, surface zooplankton daphnia magna and surface fish zebrafish , 06-3, and 40).
Fig. 4 shows experimental results for the application of the novel compounds naphthoquinone 04-4, 06-3 and 40 having excellent killing activity in the field ecosystem and results before and after application of the novel compounds.
이하 본 발명에 대하여 구체적으로 설명한다.
Hereinafter, the present invention will be described in detail.
본 발명은 특정 나프토퀴논(Naphthoquinone) 화합물의 신규 용도에 관한 것으로, 특히, 특정 나프토퀴논(Naphthoquinone) 화합물의 "유해 조류 방지 및 제어" 용도의 최초 발견에 근거한다.The present invention relates to new uses of certain naphthoquinone compounds and is based in particular on the initial discovery of "harmful algae prevention and control" applications of certain naphthoquinone compounds.
종래에는 구리(copper), Reglone A (diquat, 1,1-ethylene-2, 2-dipyridilium dibromide), 과망간산칼륨(potassium permanganate), 클로라인(chlorine), Simazine(2-chloro-4,6-bis(ethylamino)-s-triazine 등의 화학물질을 살조제(algicide)로서 수계에 직접 살포하여 유해 조류를 제어하는데 사용했다.Conventionally, copper, reglone A (diquat, 1,1-ethylene-2, 2-dipyridylium dibromide), potassium permanganate, chlorine, (ethylamino) -s-triazine were used to control harmful algae by directly spraying them with water as an algicide.
그러나 황산구리 또는 구리 유기화합물 등은 그 효과는 인정되지만 비용이 많이 소요되고 타생물에 대한 독성을 보이거나 화학물질에 의한 2차적 환경오염 등을 유발하였다. 또한 선택적인 녹조제어가 불가능하여 무해한 조류 종들에게도 광범위하게 피해를 주는 문제점을 야기시켰다. However, the effects of copper sulfate or copper organic compounds are recognized, but they are costly, toxic to other organisms, or secondary environmental pollution caused by chemicals. In addition, selective algal control was not possible, which caused extensive damage to harmless bird species.
본 발명의 특정 나프토퀴논(naphthoquinone)의 경우 담수산 유해조류의 광합성 체계(photosynthetic system)의 Q site에 작용하여 광합성을 선택적으로 저해하고, 특히 담수산 유해조류와 무해조류를 포함한 다양한 조류를 대상으로 유해종 위주의 선택적 녹조제어 효과를 가진다. 따라서 종래 살조제의 대표격인 황산구리와 유기구리화합물의 비 선택적 조류제어로 인한 광범위한 피해를 최소화할 수 있는 장점이 있다.
The naphthoquinone of the present invention selectively inhibits photosynthesis by acting on the Q site of the photosynthetic system of the marine algae, and in particular, various algae including marine algae and non-algae , It has the effect of controlling the selective greenery of harmful species. Therefore, there is an advantage that the extensive damage caused by the non-selective algae control of copper sulfate and organic copper compound, which are representative of the conventional phosgene, can be minimized.
본 발명은 일 관점에서 하기 화학식 1로 나타내는 나프토퀴논 화합물의 유해조류 제어 용도에 관한 것이다. In one aspect, the present invention relates to a harmful algae control use of a naphthoquinone compound represented by the following formula (1).
(화학식 1)(Formula 1)
상기 식 중, Wherein,
R1 및 R2는 각각 독립적으로 부존재하거나, H 또는 C1~C4 알킬이고,R 1 and R 2 are each independently absent or H or C 1 -C 4 alkyl,
R3는 치환 또는 비치환 , CH, NH, SH, CH2-NH, 또는 CH=N이고, R 3 is a substituted or unsubstituted And, CH, NH, SH, CH 2 -NH, or CH = N,
R4는 부존재하거나, 수소, 치환 또는 비치환된 C1~C12 알킬, 치환 또는 비치환 (헤테로)사이클로알킬, (헤테로)사이클로알케닐 또는 (헤테로)아릴이며,R 4 is absent or is hydrogen, substituted or unsubstituted C 1 -C 12 alkyl, substituted or unsubstituted (hetero) cycloalkyl, (hetero) cycloalkenyl or (hetero)
점선은 단일결합 또는 이중결합이다.The dotted line is a single bond or a double bond.
특히, 상기 R1 및 R2는 각각 독립적으로 부존재하거나, H 또는 CH3인 것이 바람직하다. 또한, 상기 R1과 R2가 각각 독립적으로 부존재할 경우 점선은 이중결합인 것이 바람직하고, 상기 R4의 치환된 알킬은 H, O, N, S, Cl, F, OH 또는 COOH로 치환된 것일 수 있다. 특히, R4는 이에 제한되지 않고 다양한 화학구조 형태가 위치할 수 있다.In particular, each of R 1 and R 2 is independently absent or is preferably H or CH 3 . When R 1 and R 2 are not independently present, the dotted line is preferably a double bond, and the substituted alkyl of R 4 is substituted with H, O, N, S, Cl, F, OH or COOH Lt; / RTI > In particular, R < 4 > is not limited thereto and various chemical structural forms can be located.
일 구체예들로써, In one embodiment,
상기 R1이 CH3이고, R2는 부존재, R3가 인 경우, 상기 R4는 부존재할 수 있고, R 1 is CH 3 , R 2 is absent, R 3 is , R < 4 > may be absent,
상기 R3이 CH인 경우, 상기 R3와 R4 사이에 이중결합이 형성되어 있을 수 있으며,When R 3 is CH, a double bond may be formed between R 3 and R 4 ,
상기 R1 및 R2는 각각 독립적으로 부존재하거나, H 또는 CH3이고, R3가 CH2-NH 또는 CH=N인 경우, R 1 and R 2 are each independently absent or are H or CH 3 and R 3 is CH 2 -NH or CH═N,
상기 R4는 OCH3, , , , , , 또는 로 이루어진 군중에서 선택될 수 있는데, 이 때, 상기 R5는 O 또는 S이고; 상기 R6은 Cl, SO2-CH3, OCH3, NO2, OCH2CH3, F, (CH3)p 또는 부존재하고, 상기 p는 1 또는 2이며; 상기 R7은 CH3 또는 NO2일 수 있다.Wherein R 4 is OCH 3, , , , , , or , Wherein R < 5 > is O or S; R 6 is Cl, SO 2 -CH 3 , OCH 3 , NO 2 , OCH 2 CH 3 , F, (CH 3 ) p or absent, and p is 1 or 2; The R 7 may be CH 3 or NO 2 .
또한, 상기 R1이 OCH3, R2은 부존재, R3은 CH인 경우, 상기 R4는 OCH3, 또는 일 수 있다.
When R 1 is OCH 3 , R 2 is absent and R 3 is CH, R 4 is OCH 3 or Lt; / RTI >
상기 R1과 R2가 각각 독립적으로 부존재, H, 또는 CH3이고, 상기 R3이 S인 경우, 상기 R4는 , 또는 일 수 있으며,
Wherein when R 1 and R 2 are each independently absent, H, or CH 3 , and when R 3 is S, then R 4 is , or Lt; / RTI >
R1과 R2가 각각 독립적으로 부존재, H, 또는 CH3이고, 상기 R3가 NH인 경우,If R1 and R2 are each independently absent, H, or CH 3, wherein R 3 is NH,
상기 R4는 이며, 이 때, 상기 R8은 치환 또는 비치환된 C1~C12 알킬, 치환 또는 비치환 (헤테로)사이클로알킬, (헤테로)사이클로알케닐 또는 (헤테로)아릴이거나(상기 n은 0 내지 11인 정수임); 또는R < 4 > And, this time, R 8 is a substituted or unsubstituted C 1 ~ C 12 alkyl, substituted or unsubstituted (hetero) cycloalkyl, (hetero) cycloalkenyl, or (hetero) aryl or (wherein n is 0 to 11, Lt; / RTI > or
R8은 CR9, OR10, NR11, NHR12, 및 Cl로 이루어진 군중에서 선택될 수 있으며, 이 때, 상기 CR9는 CH3, , , COOH, , , , , , , , , , ,또는 이고, R 8 may be selected from the group consisting of CR 9 , OR 10 , NR 11 , NHR 12 , and Cl, wherein CR 9 is CH 3 , , , COOH, , , , , , , , , , ,or ego,
상기 OR10은 OH, OCH3, OCH2CH2OH,또는 등 일 수 있으며 OR 10 is OH, OCH 3 , OCH 2 CH 2 OH, or Etc.
상기 NR11은 , , 또는 등 일 수 있으며,The NR < 11 & , , or Etc.,
상기 NHR12는 NHCH2CH3, NHCH2CH2OH, 또는 등일 수 있다. The NHR 12 is NHCH 2 CH 3, NHCH 2 CH 2 OH, or And so on.
여기서, 상기 R8의 치환된 C1~C12 알킬은 H, O, N, S, Cl, F, OH 또는 COOH로 치환될 수 있다. 특히, R8은 이에 제한되지 않고 다양한 화학구조 형태가 위치할 수 있다.The substituted C 1 -C 12 alkyl of R 8 may be substituted with H, O, N, S, Cl, F, OH or COOH. In particular, R 8 is not limited thereto and various chemical structural forms can be located.
한편, 상기 화학식 1로 표시되는 화합물을 기술하기 위해 사용된 여러 가지 용어에 대한 정의를 설명하면 다음과 같으며, 하기 기술한 용어들에 대한 정의들은 개별적이거나 또는 큰 그룹의 일부분으로서 특정 경우에 한하여 다르게 한정하지 않는 한, 본원의 전체에 걸쳐 사용된 용어에 적용된다. The definitions of the various terms used to describe the compound represented by the formula (1) are as follows, and the definitions of the terms described below are either individual or part of a larger group, Unless otherwise specified, applies to the terminology used throughout this application.
상기에서 "알킬"이란 용어는 1 내지 12개의 탄소 원자, 바람직하게는 1 내지 6개의 탄소 원자를 갖는 비치환 또는 치환된 직쇄 또는 분지쇄 탄화수소기를 나타낸다. 대표적인 비치환된 알킬기는 메틸, 에틸, 프로필, 이소프로필, n-부틸, t-부틸, 이소부틸, 펜틸, 헥실, 이소헥실, 헵틸, 4,4-디메틸펜틸, 옥틸 등을 포함한다. 치환된 알킬기는 할로, 히드록시, 시클로알킬, 알카노일, 알콕시, 알킬옥시알콕시, 알카노일옥시, 아미노, 알킬아미노, 디알킬아미노, 아실아미노, 카르바모일, 티올, 알킬티오, 알킬티오노, 술포닐, 술폰아미도, 술파모일, 니트로, 시아노, 카르복시, 알콕시카르보닐, 아릴, 알케닐, 알키닐, 아랄콕시, 구아니디노, 인돌릴, 이미다졸릴, 푸릴, 티에닐, 티아졸릴, 피롤리딜, 피리딜, 피리미딜, 피페리딜 및 모르폴리닐로 이루어진 군중에서 선택된 하나 이상에 의해 치환된 알킬기를 포함하지만, 이에 한정되지는 않는다. The term "alkyl" as used herein refers to an unsubstituted or substituted straight or branched chain hydrocarbon group having from 1 to 12 carbon atoms, preferably from 1 to 6 carbon atoms. Representative unsubstituted alkyl groups include methyl, ethyl, propyl, isopropyl, n-butyl, t-butyl, isobutyl, pentyl, hexyl, isohexyl, heptyl, 4,4-dimethylpentyl, The substituted alkyl group is optionally substituted with one or more substituents selected from the group consisting of halo, hydroxy, cycloalkyl, alkanoyl, alkoxy, alkyloxyalkoxy, alkanoyloxy, amino, alkylamino, dialkylamino, acylamino, carbamoyl, thiol, Sulfonyl, sulfamoyl, sulfamoyl, nitro, cyano, carboxy, alkoxycarbonyl, aryl, alkenyl, alkynyl, aralkoxy, guanidino, indolyl, imidazolyl, furyl, thienyl, thia But are not limited to, alkyl groups substituted by one or more members selected from the group consisting of pyrrolidyl, pyridyl, pyrimidyl, piperidyl and morpholinyl.
"알케닐"이란 용어는, 2개 이상의 탄소 원자를 갖고 이중 결합을 포함하는 임의의 상기 알킬기를 나타내며, 2 내지 4개의 탄소 원자를 갖는 것이 바람직하다.The term "alkenyl" denotes any of the alkyl groups having two or more carbon atoms and containing a double bond, and preferably has 2 to 4 carbon atoms.
"아릴"이란 용어는 고리 부분에 6 내지 12개의 탄소 원자를 갖는 모노사이클릭 또는 비사이클릭 방향족 탄화수소기, 예를 들어 페닐, 나프틸, 테트라히드로나프틸, 비페닐 및 디페닐기를 나타내고, 이들 각각은 1 내지 4개의 치환기, 예를 들어 알킬, 할로, 히드록시, 알콕시, 아실, 알카노일옥시, 임의로 치환된 아미노, 티올, 알킬티오, 니트로, 시아노, 카르복시, 카르복시알킬, 알콕시카르보닐, 카르바모일, 알킬티오노, 술포닐, 술폰아미도, 헤테로시클릴 등으로 임의로 치환될 수 있다. The term "aryl" refers to monocyclic or acyclic aromatic hydrocarbon groups having 6 to 12 carbon atoms in the ring portion such as phenyl, naphthyl, tetrahydronaphthyl, biphenyl and diphenyl groups, Each of which is optionally substituted with one to four substituents such as alkyl, halo, hydroxy, alkoxy, acyl, alkanoyloxy, optionally substituted amino, thiol, alkylthio, nitro, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, Carbamoyl, alkylthiono, sulfonyl, sulfonamido, heterocyclyl, and the like.
"사이클로알킬"이란 용어는, 3 내지 12개의 탄소 원자를 갖는 임의로 치환된 모노사이클릭, 비사이클릭 또는 트리사이클릭 탄화수소기를 나타내고, 이들 각각은 하나 이상의 치환기, 예를 들어 알킬, 할로, 옥소, 히드록시, 알콕시, 알카노일, 아실아미노, 카르바모일, 알킬아미노, 디알킬아미노, 티올, 알킬티오, 니트로, 시아노, 카르복시, 카르복시알킬, 알콕시카르보닐, 술포닐, 술폰아미도, 술파모일, 헤테로시클릴 등으로 치환될 수 있다. The term "cycloalkyl" refers to an optionally substituted monocyclic, bicyclic or tricyclic hydrocarbon group having from 3 to 12 carbon atoms, each of which may be substituted with one or more substituents such as alkyl, halo, oxo, Alkyl, alkoxy, alkoxy, alkanoyl, acylamino, carbamoyl, alkylamino, dialkylamino, thiol, alkylthio, nitro, cyano, carboxy, carboxyalkyl, alkoxycarbonyl, sulfonyl, sulfonamido, sulfamoyl , Heterocyclyl, and the like.
"헤테로사이클로"란 용어는 임의로 치환된 완전 포화 또는 불포화, 방향족 또는 비방향족 사이클릭기를 나타내는 고리계로서, 하나 이상의 탄소 원자를 포함하는 고리에 하나 이상의 헤테로 원자를 갖는다. 헤테로원자를 포함하는 헤테로사이클릭기의 각 고리는 질소 원자, 산소 원자 및 황 원자로부터 선택되는 1, 2 또는 3개의 헤테로원자를 가질 수 있고, 헤테로사이클릭기는 헤테로원자 또는 탄소 원자에 결합될 수 있다. The term "heterocyclo" is a ring system representing an optionally substituted fully saturated or unsaturated, aromatic or nonaromatic cyclic group, having at least one heteroatom in the ring comprising at least one carbon atom. Each ring of the heterocyclic group containing a hetero atom may have 1, 2 or 3 hetero atoms selected from a nitrogen atom, an oxygen atom and a sulfur atom, and the heterocyclic group may be bonded to a hetero atom or a carbon atom have.
구체적으로 본 발명에 따른 유해조류 제어용 조성물은 하기 [NQ01-1] 내지 [NQ49-p]로 표시되는 화합물 중에서 선택되는 화합물 또는 그의 염을 유효성분으로 포함한다.
NQ01-1 NQ01-2A
NQ01-4 NQ01-3
NQ01-6A NQ02-1
NQ02-2A NQ02-4
NQ02-3 NQ02-5
NQ03-1 NQ03-2A
NQ03-4 NQ03-3
NQ04-1 NQ04-2A
NQ04-4 NQ04-3
NQ05-1 NQ05-2A
NQ05-4 NQ05-3
NQ06-1 NQ06-2A
NQ06-4 NQ06-3
NQ07-1 NQ07-2A
NQ07-4 NQ07-3
NQ08-1 NQ08-2A
NQ08-4 NQ09-1
NQ09-2A NQ09-4
NQ09-3 NQ09-6A
NQ09-5 NQ10-1
NQ10-2A NQ10-4
NQ10-3 NQ10-6A
NQ10-5 NQ11-1
NQ11-2A NQ11-4
NQ11-3 NQ12-1
NQ12-2A NQ12-4
NQ12-3 NQ13-1
NQ13-2A NQ13-4
NQ13-3 NQ14-1
NQ14-2A NQ14-4
NQ14-3 NQ15-4
NQ15-3 NQ16-4
NQ16-3 NQ17-4
NQ17-3 NQ18-4
NQ18-3 NQ19-4
NQ19-3 NQ20-4
NQ20-3 NQ22-4
NQ22-3 NQ23
NQ24 NQ25
NQ26 NQ27
NQ28 NQ29
NQ30 NQ31
NQ32 NQ33
NQ34 NQ35
NQ36 NQ37
NQ38 NQ39
NQ40 NQ41
NQ42 NQ43
NQ44 NQ45
NQ46 NQ47
NQ48 NQ49
NQ50 NQ51
NQ52 NQ53
NQ54 NQ55
NQ38-p NQ40-p
NQ46-p NQ47-p
NQ49-p
Specifically, the composition for controlling harmful birds according to the present invention contains, as an active ingredient, a compound selected from compounds represented by the following [NQ01-1] to [NQ49-p] or salts thereof.
NQ01-1 NQ01-2A
NQ01-4 NQ01-3
NQ01-6A NQ02-1
NQ02-2A NQ02-4
NQ02-3 NQ02-5
NQ03-1 NQ03-2A
NQ03-4 NQ03-3
NQ04-1 NQ04-2A
NQ04-4 NQ04-3
NQ05-1 NQ05-2A
NQ05-4 NQ05-3
NQ06-1 NQ06-2A
NQ06-4 NQ06-3
NQ07-1 NQ07-2A
NQ07-4 NQ07-3
NQ08-1 NQ08-2A
NQ08-4 NQ09-1
NQ09-2A NQ09-4
NQ09-3 NQ09-6A
NQ09-5 NQ10-1
NQ10-2A NQ10-4
NQ10-3 NQ10-6A
NQ10-5 NQ11-1
NQ11-2A NQ11-4
NQ11-3 NQ12-1
NQ12-2A NQ12-4
NQ12-3 NQ13-1
NQ13-2A NQ13-4
NQ13-3 NQ14-1
NQ14-2A NQ14-4
NQ14-3 NQ15-4
NQ15-3 NQ16-4
NQ16-3 NQ17-4
NQ17-3 NQ18-4
NQ18-3 NQ19-4
NQ19-3 NQ20-4
NQ20-3 NQ22-4
NQ22-3 NQ23
NQ24 NQ25
NQ26 NQ27
NQ28 NQ29
NQ30 NQ31
NQ32 NQ33
NQ34 NQ35
NQ36 NQ37
NQ38 NQ39
NQ40 NQ41
NQ42 NQ43
NQ44 NQ45
NQ46 NQ47
NQ48 NQ49
NQ50 NQ51
NQ52 NQ53
NQ54 NQ55
NQ38-p NQ40-p
NQ46-p NQ47-p
NQ49-p
삭제delete
삭제delete
삭제delete
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특히, 상기 [NQ01-1] 내지 [NQ49-p]로 표시되는 화합물 중에서 바람직하게는 01-4, 01-3, 02-4, 02-3, 03-4, 03-3, 04-4, 04-3, 05-4, 05-3, 06-3, 07-4, 07-3, 09-4, 09-3, 10-3, 11-4, 11-3, 15-4, 15-3, 16-4, 18-4, 19-4, 19-3, 22-4, 26, 27, 32, 35, 38, 40, 41, 42, 44, 45, 46, 47, 48, 49, 52, 53, 38-p, 40-p, 46-p, 47-p 등은 1 μM 이하의 미량의 농도에서 IC50값을 보여 우수한 살조 효과를 확인하였다. 가장 바람직하게는 01-4, 01-3, 03-3, 04-4, 04-3, 05-4, 06-3, 09-4, 15-4, 15-3, 18-4, 22-4, 40, 47, 48 등의 화합물을 포함한다.Among the compounds represented by the above-mentioned [NQ01-1] to [NQ49-p], preferably, the compounds represented by the above formulas are 01-4, 01-3, 02-4, 02-3, 03-4, 03-3, 04-4, 04-3, 05-4, 05-3, 06-3, 07-4, 07-3, 09-4, 09-3, 10-3, 11-4, 11-3, 15-4, 15- 3, 16-4, 18-4, 19-4, 19-3, 22-4,26, 27,32,35,38,40,41,42,44,45,46,47,48,49, 52, 53, 38-p, 40-p, 46-p and 47-p showed IC50 values at a trace concentration of 1 μM or less. Most preferably 01-4, 01-3, 03-3, 04-4, 04-3, 05-4, 06-3, 09-4, 15-4, 15-3, 18-4, 22- 4, 40, 47, 48, and the like.
특히, 남조류에 대해서 01-4(300 nM), 06-3(160 nM), 40(160 nM), 15-3 (170 nM), 02-3(190 nM), 15-3(170 nM), 19-4(290 nM), 22-4(380 nM), 46(370 nM), 47(170 nM), 48(130 nM), 49(220 nM)가 살조 효과가 더욱 우수하였고, 규조류에 대해서는 01-4(280nM), 02-3(390 nM), 04-4(170 nM), 04-3(170 nM), 05-4(440 nM), 09-4(250 nM), 10-3(410 nM), 15-3(420 nM), 18-4(170 nM), 22-4(40 nM), 41(400 nM)가 살조 효과가 더욱 우수하였다.
In particular, for the cyanobacteria, the concentrations of 01-4 (300 nM), 06-3 (160 nM), 40 (160 nM), 15-3 (170 nM), 02-3 (190 nM) , 19-4 (290 nM), 22-4 (380 nM), 46 (370 nM), 47 (170 nM), 48 (130 nM) 04-4 (170 nM), 05-4 (440 nM), 09-4 (250 nM), 10-4 (170 nM) 3 (410 nM), 15-3 (420 nM), 18-4 (170 nM), 22-4 (40 nM) and 41 (400 nM).
또한, 상기 화합물들의 염은 본 발명의 화합물을 최종적으로 분리, 정제 및 합성하는 동안에 동일반응계에서 제조하거나 별도로 무기 염기 또는 유기 염기와 반응시켜 제조할 수 있다. Salts of the above compounds may also be prepared in situ during the final isolation, purification and synthesis of the compounds of the present invention or separately by reacting them with an inorganic base or an organic base.
상기 염으로는 본 발명의 화합물이 산성기를 함유하고 있을 경우, 염기와 염을 형성할 수 있으며, 이러한 염으로는 예를 들면, 이에 한정되지는 않으나 리튬염, 나트륨염 또는 칼륨염과 같은 알칼리금속과의 염; 바륨 또는 칼슘과 같은 알칼리토금속과의 염; 마그네슘염과 같은 기타 금속과의 염; 디시클로헥실아민과의 염과 같은 유기 염기염; 리신 또는 아르기닌과 같은 염기성 아미노산과의 염을 포함할 수 있다. The salt may form a salt with a base when the compound of the present invention contains an acid group. Examples of such a salt include an alkali metal such as a lithium salt, a sodium salt, or a potassium salt Salts with; Salts with alkaline earth metals such as barium or calcium; Salts with other metals such as magnesium salts; Organic base salts such as salts with dicyclohexylamine; And salts with basic amino acids such as lysine or arginine.
또한, 본 발명의 화합물이 분자 내에 염기성 기를 함유하는 경우에는 산부가염을 형성할 수 있으며, 이러한 산부가염의 예로는, 이에 한정되지는 않으나, 무기산, 특히 할로겐화수소산(예컨대, 불소화수소산, 브롬화수소산, 요오드화수소산 또는 염소화수소산), 질산, 탄산, 황산 또는 인산과의 염; 메탄술폰산, 트리플루오로메탄술폰산 또는 에탄술폰산과 같은 저급알킬 술폰산과의 염; 벤젠술폰산 또는 p-톨루엔술폰산과의 염; 아세트산, 푸마르산, 타르타르산, 옥살산, 말레산, 말산, 숙신산 또는 시트르산과 같은 유기카르복실산과의 염; 및 글루탐산 또는 아스파르트산과 같은 아미노산과의 염을 포함할 수 있다. In addition, when the compound of the present invention contains a basic group in the molecule, an acid addition salt can be formed. Examples of such an acid addition salt include, but are not limited to, inorganic acids such as hydrohalic acid, Hydroiodic acid or hydrochloric acid), nitric acid, carbonic acid, salts with sulfuric acid or phosphoric acid; Salts with lower alkylsulfonic acids such as methanesulfonic acid, trifluoromethanesulfonic acid or ethanesulfonic acid; Salts with benzenesulfonic acid or p-toluenesulfonic acid; Salts with organic carboxylic acids such as acetic acid, fumaric acid, tartaric acid, oxalic acid, maleic acid, malic acid, succinic acid or citric acid; And salts with amino acids such as glutamic acid or aspartic acid.
이하에서 별도의 설명이 없는 한, 용어 "본 발명에 따른 나프토퀴논 화합물" 또는 "화학식 1의 화합물"은, 화합물 그 자체, 그것의 염, 수화물, 용매화물, 이성질체 등을 모두 포함하는 개념으로 사용되고 있다.The term "naphthoquinone compound according to the present invention" or "compound of formula (1)" is a concept including both the compound itself, its salts, hydrates, solvates, isomers and the like .
용어 "수화물(hydrate)"은 비공유적 분자간력(non-covalent intermolecular force)에 의해 결합된 화학양론적(stoichiometric) 또는 비화학양론적(non-stoichiometric) 량의 물을 포함하고 있는 본 발명의 화합물 또는 그것의 염을 의미한다. The term "hydrate" refers to a compound of the present invention comprising a stoichiometric or non-stoichiometric amount of water combined by non-covalent intermolecular forces Or a salt thereof.
용어 "용매화물(solvate)"은 비공유적 분자간력에 의해 결합된 화학양론적 또는 비화학양론적 량의 용매를 포함하고 있는 본 발명의 화합물 또는 그것의 염을 의미한다. The term "solvate" means a compound of the present invention or a salt thereof, comprising a stoichiometric or non-stoichiometric amount of a solvent bound by noncovalent intermolecular forces.
용어 "이성질체(isomer)"는, 동일한 화학식 또는 분자식을 가지지만 광학적 또는 입체적으로 다른 본 발명의 화합물 또는 그것의 염을 의미한다. 예를 들어, 본 발명의 화학식 1에 따른 화합물은 치환기들의 종류에 따라서는 입체생성 중심(asymmetric center, 비대칭 탄소 원자)을 가질 수 있는 바, 이 경우 화학식 1의 화합물은 거울상 이성질체 및 부분 입체 이성질체와 같은 광학 이성질체로서 존재할 수 있다. 예를 들어, 본 발명에 따른 화합물을 제조하기 위해 사용된 치환기들의 종류, 중간체 생성물 및 제조방법의 선택에 따라 가능한 이성질체, 예컨대 실질적으로 순수한 기하학적(시스 또는 트랜스) 이성질체, 광학 이성질체(거울상체) 또는 라세미체의 형태일 수 있으며, 이러한 가능한 이성질체 모두 본 발명의 영역에 포함된다.The term "isomer" means a compound of the present invention or a salt thereof, which has the same chemical or molecular formula but is optically or sterically different. For example, the compound according to
본 발명의 상기 화학식 1의 나프토퀴논 화합물은 다음과 같은 여러 가지 메카니즘으로 녹조생물을 제어하는 것으로 판단된다. The naphthoquinone compound of
퀴논류는 redox cycling, arylation, intercalation, DNA 손상, free radical 형성, mitochondria 호흡억제 등의 다양한 작용 메카니즘에 의하여 세포독성을 나타낼 수 있다.Quinones can exhibit cytotoxicity by various mechanisms of action such as redox cycling, arylation, intercalation, DNA damage, free radical formation, and mitochondrial respiration inhibition.
특히 quinone류는 ‘oxidative stress’의 형성을 수반하게 되고, 이어서 flavo-enzyme (NADPH-cytochrom-P-450 reductase)과 mitochondrial NADH-ubiquinone oxidoreductase에 의해 semiquinone free radical이 형성된다. Semiquinone free radical로부터 다시 quinone으로 되돌아가는 과정에서 superoxide를 생성하게 되고 (Scheme 1), superoxide로부터 hydroxyl radical이 생성되는데, 이것은 DNA에 작용하여 세포분열을 억제하게 된다.In particular, quinones are accompanied by the formation of 'oxidative stress', followed by the formation of semiquinone free radicals by flavo-enzyme (NADPH-cytochrome-P-450 reductase) and mitochondrial NADH-ubiquinone oxidoreductase. In the process of returning from semiquinone free radicals back to quinones, superoxide is formed (Scheme 1), hydroxyl radicals are formed from superoxide, which acts on DNA to inhibit cell division.
Naphthoquinone 골격을 갖고 있는 약물들은 redox cycling, intercalation 등의 작용 메카니즘 외에 DNA 복제에 관여하는 topoisomerase에 작용하여 세포분열억제효과를 나타내는 것으로 알려졌다. Naphthoquinone계 약물 등 현재 사용되어지고 있는 많은 약물들은 DNA에 결합함으로써 DNA의 복제 및 전사를 억제하는 intercalation 현상에 의해 주로 세포들을 살멸하는 것으로 알려져 왔으나 최근의 연구결과를 보면 intercalation이라는 현상은 세포분열억제효과를 나타내는 여러 단계의 작용 메카니즘 중 단지 첫 번째 단계일 뿐이며, 대부분의 intercalating 약물들은 DNA 복제에 관여하는 topoisomerase Ⅱ라는 효소를 억제함으로써 세포분열억제효과를 나타내는 것으로 밝혀지고 있다. The drugs with Naphthoquinone skeleton are known to act on topoisomerase, which is involved in DNA replication, as well as mechanisms of action such as redox cycling and intercalation, thereby exhibiting cell division inhibition. Naphthoquinone-based drugs have been known to kill cells mainly by intercalation that inhibits DNA replication and transcription by binding to DNA. However, recent research has shown that intercalation is an effect of inhibiting cell division , And most of the intercalating drugs have been shown to inhibit cell division by inhibiting the enzyme called topoisomerase II, which is involved in DNA replication.
DNA topoisomerase는 DNA의 형태를 변형시키는 효소들이다. 핵안의 DNA는 꼬인 상태로 쌓여 (chromatin) 있으므로 replication, transcription, repair 등 그 기능이 진행되기 위해서는 그 꼬임 상태를 일시적으로 풀어주는 단계가 필요하다. 이 역할을 DNA topoisomerase가 담당한다. 모든 prokaryotic과 eukaryotic 세포에 DNA topoisomerase가 존제하며, 이 효소는 type Ⅰ과 type Ⅱ로 분류된다. Topoisomerase Ⅰ은 일시적으로 DNA의 한쪽 골격을 절단하여 DNA의 비틀림을 풀리게 하고, 반면에 topoisomerase Ⅱ는 DNA의 양쪽 골격을 동시에 절단하여 이중나선 DNA의 knotting/unknotting 및 catenation/decatenation을 허용하도록 촉매 한다. Topoisomerase Ⅱ는 DNA 합성에 이어 다른 DNA를 분리하므로 세포의 proliferation에 밀접한 관련이 있다. 그러므로 이 효소의 활성저지는 곧 세포증식의 중지를 뜻한다.
DNA topoisomerases are enzymes that alter the shape of DNA. Since the DNA in the nucleus is chronically twisted, replication, transcription, repair, and other functions require a step to temporarily release the twisted state. This role is played by the DNA topoisomerase. DNA topoisomerase is present in all prokaryotic and eukaryotic cells, and these enzymes are classified as type Ⅰ and type Ⅱ. Topoisomerase I transiently cleaves one strand of DNA to loosen the DNA strand while topoisomerase II cleaves both strands of DNA simultaneously to allow knotting / unknotting and catenation / deconatation of double stranded DNA. Topoisomerase II is closely related to the proliferation of cells since it separates DNA after synthesis. Therefore, the enzyme 's inhibition of activity means the cessation of cell proliferation.
본 발명에 따른 상기 화학식 1의 화합물은 당업계에 알려진 방법, 이의 변형된 방법 또는 본 발명에 의한 방법으로 제조하여 사용할 수 있으며, 상업적으로 판매하는 것을 구입하여 사용할 수도 있다.The compound of formula (I) according to the present invention may be prepared by a method known in the art, a modified method thereof, or a method according to the present invention, or a commercially available compound may be used.
상기 제조과정에서 사용될 수 있는 반응용매로는 반응에 관여하지 않는 한 특별한 제한은 없으며, 예를 들면 디에틸 에테르, 테트라히드로푸란, 디옥산 등의 에테르류; 디클로로메탄, 클로로포름 등의 할로겐화 탄화수소류; 피리딘, 피페리딘, 트리에틸아민 등의 아민류, 아세톤; 메틸에틸케톤, 메틸이소부틸 등의 알킬케톤류; 메탄올, 에탄올, 프로판올 등의 알코올류; N,N-디메틸포름아미드, N,N-디메틸아세트아미드, 아세토니트릴, 디메틸술폭시드, 헥사메틸인산트리아미드 등의 비프로톤성 극성용매를 들 수 있으며, 특히 통상적으로 유기합성에서 사용되는 비반응성 유기용매 중에서 딘-스탁 트랩에 의해 반응 중 생성되는 물을 분리할 수 있는 용매가 선호된다. 이러한 용매의 예로는, 벤젠, 톨루엔, 크실렌 등이 있으나 이에 한정되지는 않는다. 반응 생성물의 분리 및 정제는 유기합성에서 통상적으로 수행되는 농축, 추출 등의 과정을 통해 이루어지며, 필요에 따라 실리카겔 상에서 컬럼 크로마토그래피에 의한 정제 작업을 통해 분리 및 정제를 수행할 수 있다. The reaction solvent which can be used in the above-mentioned production process is not particularly limited as long as it does not participate in the reaction, for example, ethers such as diethyl ether, tetrahydrofuran and dioxane; Halogenated hydrocarbons such as dichloromethane and chloroform; Amines such as pyridine, piperidine and triethylamine, acetone; Alkyl ketones such as methyl ethyl ketone and methyl isobutyl; Alcohols such as methanol, ethanol and propanol; Aprotic polar solvents such as N, N-dimethylformamide, N, N-dimethylacetamide, acetonitrile, dimethylsulfoxide and hexamethylphosphoric triamide. Particularly, non-reactive Solvents capable of separating the water produced during the reaction by the Dean-Stark trap in organic solvents are preferred. Examples of such solvents include, but are not limited to, benzene, toluene, xylene, and the like. The separation and purification of the reaction product are carried out through concentration, extraction and the like which are usually carried out in organic synthesis. Separation and purification can be carried out by purification by column chromatography on silica gel, if necessary.
본 발명은 또한 본 발명에 따른 상기 화학식 1의 화합물 제조방법들에 대한 임의의 변형을 포함하고, 여기서 그의 임의의 단계에서 수득할 수 있는 중간체 생성물은 나머지 단계들의 출발물질로 사용될 수 있으며, 상기 출발물질은 반응 조건하에 반응계 내에서 형성되거나, 반응 성분들은 그의 염 또는 광학적으로 거울상체의 형태로 사용될 수 있다. The present invention also includes any modifications to the methods of making the compounds of
따라서, 본 발명은 다른 관점에서 상기 화학식 1의 화합물을 제조하는 방법에 관한 것이다. 상기 제조방법은 그것의 예시적인 방법에 지나지 않으며, 당해 분야의 기술에 근간한 다양한 방법들에 의해 적절히 변형시켜 사용할 수 있다.예를 들면, 본 발명에 따른 비-예시된 화합물의 분리 및 정제는 당분야의 숙련가에게 명백한 변형에 의해, 예를 들면, 간섭기를 적절히 보호하거나, 당분야에 공지된 다른 적당한 시약으로 교체하거나, 또는 반응 조건을 통상적으로 변화시킴으로써 성공적으로 수행될 수 있다. Accordingly, the present invention relates to a process for preparing the compound of formula (I) from a different viewpoint. For example, the separation and purification of the non-exemplified compounds according to the present invention can be carried out in a variety of ways, including, but not limited to, Can be successfully accomplished by variations that are apparent to those skilled in the art, for example by appropriately protecting the interferor, replacing it with other suitable reagents known in the art, or by changing the reaction conditions conventionally.
본 발명이 속하는 분야에서 통상의 지식을 가진 자라면, 본 발명에 따른 화합물 A의 제조를 위한 구체적인 반응조건 등을 추후 설명하는 제조예들과 실시예들을 통해 확인할 수 있으므로, 그에 대한 자세한 설명은 생략한다.
As a person skilled in the art to which the present invention pertains, the specific reaction conditions and the like for the preparation of the compound A according to the present invention can be confirmed through the following production examples and examples, do.
(유해조류)(Harmful bird)
한편, 조류(algae)는 바닷물 또는 민물에서 서식하면서 생태계에 많은 영향을 주는데, 본 발명에서 유해조류(harmful algae)란 이하와 같은 악영향을 끼치는, 녹조 또는 적조현상을 야기시켜 수중환경 및 경제활동에 악영향을 미치는 조류를 말한다. On the other hand, algae live in seawater or fresh water and have a great impact on the ecosystem. In the present invention, harmful algae are caused by algae or red tide, which have the following adverse effects, It is a bird that has an adverse effect.
i) 착색 또는 스컴 형성, 죽은 물고기 등으로 시각적인 불쾌감 유발 및 레크레이션 활동의 저해 i) Inhibition of visual discomfort and recreational activity by coloration or scum formation, dead fish, etc.
ii) 독소에 의한 인체 및 가축에의 건강상의 손상, 악취로 불쾌감 유발ii) health damage to human body and livestock due to toxin, unpleasant odor
iii) 생태계 파괴로 인하 토종 동물의 사멸 또는 서식처 이동, 개체군 변화, 먹이 손실iii) Death or habitat migration, population change, food loss due to degradation of native ecosystems
iv) 레크레이션 활동 및 여행의 저하로 인해 지역 경제적 손실, 먹는 물, 농업용수, 산업용수 부족으로 인한 경제적 손실iv) economic losses due to local economic losses, food, agricultural water, and industrial water shortages due to recreational activities and travel degradation;
v) 독소물질에 의한 가축이나 야생동물의 폐사, 대량증식한 조류의 분해 동안 수중 용존산소 감소로 인한 물고기 및 수중생물의 폐사v) The death of fish and aquatic organisms due to the reduction of dissolved oxygen in the water during the decomposition of livestock and wildlife by toxins,
vi) 경제적 가치가 있는 종들 (연어류와 송어류)에 악취를 발생
vi) Odorous odors of economically valuable species (salmon and trout)
적조현상은 육지로부터 유기오염 물질이나 질소 인 등이 바다로 다량 유입되어 플랑크톤의 비정상적인 증식으로 인해 바다의 색깔이 적색, 적갈색, 황갈색, 녹색, 황녹색 및 황색 등으로 변하는 현상을 말한다. 이러한 적조를 일으키는 원인생물은 주로 편모조류 및 규조류이며, 이 외에도 섬모충류, 남조류 및 적색세균 등이 적조를 유발시키는 것으로 알려져 있다. Red tide phenomenon refers to the phenomenon that the color of the sea changes to red, reddish brown, yellowish brown, green, yellow green and yellow due to abnormal growth of plankton due to a large influx of organic pollutants or nitrogen phosphorus from the land into the sea. Cyanobacteria, diatoms, and red bacteria are known to cause red tides.
또한 최근 들어 적조현상은 산업화의 발전에 따라 해양 오염물의 증가로 인해 전 세계적으로 증가 추세에 있는데, 우리나라의 경우에도 1961년 진해만 부근의 진동만에서 적조가 목격된 이래 1970년대에는 104건의 적조가 진해만 일대에서 발생했으며, 1995년 이후 매년 남해안과 남동해안에서 적조가 발생하고 있는 실정이다. Recently, red tide phenomenon has been increasing worldwide due to the increase of marine pollutants due to the development of industrialization. In the case of Korea, red tide was observed in 1961 in Gimhae Bay near Jinhae Bay. In the 1970s, 104 red tide , And since 1995, red tides have been occurring in the south coast and the south east coast every year.
한편, 적조가 발생하게 되면 수중의 용존 산소가 결핍되어 바다는 순식간에 산소가 희박한 상태가 되어 물고기 및 어폐류가 대량 폐사하게 되고, 대량 번식된 플랑크톤은 물고기의 아가미에 붙어서 물고기를 질식시키기도 하며, 특히 편모조류인 코콜리디니움은 유해 독소를 발생시켜 물고기의 죽음을 초래하게 된다. 또한 현재 세계 20억 이상의 인구가 소비하는 동물성 단백질의 50% 가량은 바다에서 공급되는데 적조현상에 따른 해양생태계의 파괴는 이러한 식량자원에도 심각한 영향을 미치게 되며, 나아가 수역 이용 가치를 저하시키고, 더 나아가 경제적인 가치를 초월하여 커다란 환경 문제를 야기하게 된다. On the other hand, when red tide occurs, dissolved oxygen is deficient in the water, and the sea becomes oxygen-lean state in a short time, causing massive deaths of fish and fish species, and mass propagation of plankton is attached to the gills of fish to choke fish, In particular, coccolliminum, a flagella algae, causes harmful toxins, resulting in the death of fish. In addition, about 50% of the animal protein consumed by more than 2 billion people in the world is supplied from the sea. The destruction of marine ecosystem due to red tide will seriously affect these food resources, further deteriorating water use value, It transcends economic value and causes big environmental problems.
본 발명은 이러한 적조를 일으키는 원인생물인 편모조류 및 규조류, 남조류 등에 대하여 살조효과를 가진다.
The present invention has a killing effect on algae, diatoms, cyanobacteria and the like which are causative agents of red tide.
그러나, 본 발명은 이러한 적조현상뿐만 아니라, 녹조현상에 대한 증식 억제에 특히 바람직하다.However, the present invention is particularly preferable for suppressing the proliferation of not only the red tide phenomenon but also the green tide phenomenon.
녹조현상이란 부영양화된 호수나 유속이 느린 하천에서 부유성의 조류, 즉, 식물플랑크톤이 대량 증식하여 수면에 집적함으로써 물색을 현저하게 녹색으로 변화시키는 현상을 가리키는 말이다. 녹조현상은 수질 부영양화의 상징적인 현상으로 심한 이취미를 유발시키며 독성물질을 생성하는 등 수자원으로서의 가치는 물론 전체 수중 생태계의 균형과 질서를 파괴한다A green algae phenomenon is a phenomenon in which a floating bird, that is, a phytoplankton, in an eutrophic lake or a stream with a slow flow rate, massively replicates and accumulates on the surface of water, thereby significantly changing the color of the water. The algae phenomenon is a symbolic phenomenon of water eutrophication, which causes severe hobbies and destroys the balance and order of the whole aquatic ecosystem, as well as its value as a water source, by producing toxic substances
이러한 녹조현상은 일반적으로 담수에서만 발생하는데 공장폐수와 생활하수, 비료, 농약, 가축과 사람의 분뇨 등등 각종 육상 오염물질들이 강 또는 호수로 유입되고 수역의 하부에 침작되어 박테리아에 의해 분해되며 분해된 유기물들이 플랑크톤의 먹이가 되는 질소와 인을 생성시켜 해수 및 담수에서 녹조가 발생하게 된다. 이러한 녹조는 수중의 용존산소를 감소시키며, 독성녹조 및 각종 녹조플랑크톤을 생성시켜 어류 및 수생생물을 폐사시키고, 또한 육지로부터 대량 유입된 유기물들이 침전된 수역 저부에는 침전된 중금속들이 수중으로 용출되어 담수를 오염시키고 어류를 중독시킬 수 있으며, 나아가서는 환경파괴 및 자연 미관의 손상 등 많은 문제점을 불러일으키게 된다.These green algae occur only in fresh water, and are caused by the infiltration of various land pollutants such as industrial wastewater, domestic sewage, fertilizer, pesticides, livestock and human manure into rivers or lakes, decomposed by bacteria, Organisms generate nitrogen and phosphorus, which feed on plankton, and green tides occur in seawater and fresh water. These green algae reduce the dissolved oxygen in the water, produce toxic green algae and various kinds of algae plankton to kill fishes and aquatic organisms, and precipitate heavy metals in the bottom of the watery sediments, And can poison the fish. Furthermore, it causes many problems such as environmental damage and damage to the natural beauty.
전 세계적으로 녹조에 의한 동물의 피해는 1878년 영국의 Francis에 의해 처음으로 보고되었다. 그 후 1900년대에 접어들어 선진국을 중심으로 많은 나라에서 녹조에 의한 피해가 급속히 보고되기 시작하였다(표 2). 특히 Microcystis , Anabaena, Oscillatoria 등 독성물질을 배출하는 남조류에 의한 피해가 대부분을 차지하고 있으며, 북미대륙과 스웨덴, 영국 등의 유럽, 남아프리카, 중동지역, 한국, 일본, 중국 등 극동아시아 등등 전 세계에서 녹조가 발생되지 않는 지역은 거의 없으며, 특히 우리나라의 경우, 동물과 인간에 대한 피해조사가 체계적으로 이루어지지 않아 보건학적, 그리고 경제적 피해규모조차 확인되지 않고 있는 형편이다.Worldwide, animal damage caused by algae was first reported by Francis of England in 1878. In the 1900s, damage from green algae began to be reported rapidly in many countries, especially in developed countries (Table 2). Especially Microcystis , Anabaena, Oscillatoria And most of them are caused by cyanobacteria that emit toxic substances, and areas where green tides do not occur in the world such as North America, Sweden, UK, Europe, South Africa, Middle East, Korea, Japan, In the case of Korea, there is no systematic investigation of damage to animals and humans, so the health and economic damages are not even confirmed.
(표 2)(Table 2)
그리고, 우리나라와 같이 온대지방의 부영양화 되어 있는 수생태계에서는 풍부한 영양분을 바탕으로 식물플랑크톤 같은 1차 생산자의 생장에 유리한 환경이 조성되면서 조류의 대발생이 폭발적으로 매년 반복되고 있다. 특히, 우리나라 하천 및 호수에서 발생하는 녹조(algal blooming)는 주로 여름철의 남조류(cyanobacteria) 및 봄·겨울철의 규조류(diatom)가 녹조현상의 주요 종이지만 지역에 따라 와편모조나 소형 cryptomonad등 다양한 조류 종에 의해서 발생되어진다.And, in the eutrophic aquatic ecosystem such as Korea, the ecosystem of the eutrophic continent has an abundant nutrient based on the environment of favorable growth of the primary producers such as phytoplankton, and the outbreak of algae is repeated every year explosively. In particular, algal blooming occurring in rivers and lakes in Korea is mainly caused by cyanobacteria in summer and diatom in spring and winter. However, various algal blooms such as cryptomonad, Lt; / RTI >
(표 3 -녹조현상을 일으키는 주요 담수조류 종과 그 특징)(Table 3 - Major species of freshwater algae causing its algae phenomenon and its characteristics)
(표 3)(Table 3)
상기 녹조현상은 수질 부영양화의 상징적인 현상으로 심한 이취미를 유발시키며 독성물질을 생성하는 등 수자원으로서의 가치는 물론 전체 수중 생태계의 균형과 질서를 파괴한다The green algae phenomenon is a symbolic phenomenon of water eutrophication, which causes serious hobbies and creates poisonous substances, destroying the balance and order of the whole aquatic ecosystem as well as its value as water resources
본 발명에 따른 화학식 1의 화합물을 포함하는 조성물은 연못, 저수지, 호수, 호소, 하천 또는 강 등 담수 또는 기수역에서 미세조류(남조강, 규조강, 녹조강, 유글레조강, 와편모조강 및 황색편모조강, 갈색편모조강, 홍조강)의 이상 증식으로 유발되는 녹조발생을 더욱 효과적으로 제어 가능하다.
The composition containing the compound of formula (I) according to the present invention can be used for the preparation of micro-algae (Nam-Joo River, Diatomaceous Sea, Green River, Yugurejo River, It is possible to more effectively control the occurrence of green tides caused by an abnormal proliferation of crude steel, crude brown rice crude steel, and red flour.
이러한 녹조 및 적조 현상을 나타내는 유해조류 중에서 본 발명의 살조 효과를 나타낼 수 있는 유해조류로는 남조강, 규조강, 녹조강, 유글레조강, 와편모조강, 황색편모조강, 갈색편모조강 또는 홍조강 조류를 포함한다.Of the harmful birds exhibiting the green tide and red tide phenomenon, harmful algae that can exhibit the killing effect of the present invention include Namchogang, Diatomaceous ginseng, Green river, Yugurejo river, Wrappeed mudstone, Yellow flagellum, .
특히, 상기 남조강(Cyanophyceae) 조류는 마이크로시스티스(Microcystis), 아나베나(Anabaena), 아파니존메논(Aphanizomenon), 오실라토리아(Oscillatoria) 또는 워로니키니아(Woronichinia)속 조류 등일 수 있고, 바람직하게는 마이크로시스티스 속 또는 아나베나 속 조류이다.In particular, the Cyanophyceae algae may be Microcystis, Anabaena, Aphanizomenon, Oscillatoria or Woronichinia species birds, and the like. Is a species of the genus Microsystus or anabenaceae.
상기 규조강(Bacillariophyceae) 조류는 스테파노디스커스(Stephanodiscus), 사이클로텔라(Cyclotella), 사이클로스테파노스(Cyclostaphanos), 아울라코세이라(Aulacoseira), 멜로지라(Melosira), 탈라지오지라(Thalassiosira), 케토세로스(Chaetoceros) 스켈레토네마(Skeletonema), 아크난테스(Achnanthes), 아스테리오넬라(Asterionella), 아칸토세라스(Acanthoceras), 나비큘라(Navicula), 니츠취아(Nitzschia), 디플로네시스(Diploneis), 심벨라(Cymbella), 곰포네마(Gomphonema), 수리렐라(Surirella), 시네드라(Synedra), 프레즐라리아(Fragilaria), 실린드로세카(Cylindrotheca), 유캄피아(Eucampia), 코스마리움(Cosmarium), 또는 타벨라리아(Tabellaria) 속 조류 등일 수 있고, 바람직하게는 스테파노디스커스, 사이클로텔라, 또는 아울라코세이라이다.The Bacillariophyceae algae may be selected from the group consisting of Stephanodiscus, Cyclotella, Cyclostaphanos, Aulacoseira, Melosira, Thalassiosira, Chaetoceros Skeletonema, Achnanthes, Asterionella, Acanthoceras, Navicula, Nitzschia, Diploneis, Cymbella, Gomphonema, Surirella, Synedra, Fragilaria, Cylindrotheca, Eucampia, Kosumerium, Crombie, Cosmarium, or a species of the genus Tabellaria and the like, preferably a Stephanos discus, a Cyclotella, or an Arucocera.
상기 녹조강(Chlorophyceae) 조류는 클로스테리옵시스(Closteriopsis), 클로스테리움(Closterium), 하이드로테카(Hydrotheca), 스피로기라(Spirogyra), 고나토지곤(Gonatozygon), 액티나스트륨(Actinastrum), 마이크락티니움(Micractinium), 라걸헤이미어(Lagerheimia), 웨스텔라(Westella), 유도리나(Eudorina), 판도리나(Pandorina), 볼복스(Volvox), 딕티오스페리움(Dictyospaerium), 클라로코쿰(Chlorococcum), 보트리오코쿠스(Botryococcus), 스타우라스트륨(Staurastrum), 클로스테리움(Closterium), 모노라피디움(Monoraphidium), 안키스트로데스무스(Ankistrodesmus), 컬크네리엘라(Kirchneriella), 페디아스트룸(Pediastrum), 세네데스무스(Scenedesmus), 코엘라스트륨(Coelastrium), 클라미도모나스(Clamydomonas), 클로렐라(Chlorella), 또는 클로렐라(Chlorella)속 조류 등일 수 있다.The Chlorophyceae algae may be selected from the group consisting of Closteriopsis, Closterium, Hydrotheca, Spirogyra, Gonatozygon, Actinastrum, And may be used in conjunction with other devices such as Micractinium, Lagerheimia, Westella, Eudorina, Pandorina, Volvox, Dictyospaerium, Such as Chlorococcum, Botryococcus, Staurastrum, Closterium, Monoraphidium, Ankistrodesmus, Kirchneriella, , Pediastrum, Scenedesmus, Coelastrium, Clamydomonas, Chlorella, or Chlorella species, and the like.
상기 유글레나조강(Euglenophyceae) 조류는 트라켈로모나스(Trachelomonas), 파커스(Phacus), 또는 유글레나(Euglena)속 조류 등을 포함하고, 상기 와편모조강(Dinophyceae) 조류는 페리디늄(Peridinium), 세라티움(Ceratium)속 조류 등을 포함한다.The Euglenophyceae algae include Trachelomonas, Phacus, or Euglena algae, and the dinophyceae algae include peridinium, sera, And Ceratium algae.
상기 황색편모조강(Chrysophyceae) 조류는 디노브리온(Dinobryon), 유로글레나(Uroglena), 시누라(Synura) 및 말로모나스(Mallomonas)속 조류 등을 포함하고, 상기 갈색편모조강(Cryptophyceae) 조류의 경우 크립토모나스(Cryptomonas) 조류 등을 포함하고, 상기 홍조강(Phodophyceae) 조류의 경우 로도모나스(Rhodomonas)속 조류 등을 포함한다. The yellow Chrysophyceae algae include Dinobryon, Uroglena, Synura and Mallomonas birds, and the Cryptophyceae algae are selected from the group consisting of Cryptomonas birds and the like, and in the case of Phodophyceae birds, Rhodomonas birds and the like.
이들에 대하여, 상기 화학식 1로 표시되는 본 발명의 화합물들이 녹조 및 적조현상들을 방지할 수 있는 효과가 있는지 확인한 결과, 상기 화학식 1로 표시되는 화합물들이 유해조류를 살조하는 효과가 있음을 확인하였다.
As a result of confirming that the compounds of the present invention represented by the formula (1) have an effect of preventing green tide and red tide phenomenon, it was confirmed that the compounds of the formula (1) were effective in killing harmful birds.
일 구체예로서, 본 발명은 상기 화학식 1로 표시되는 화합물 또는 그의 염을 유효성분으로 포함하는 유해조류 방제용 조성물을 제공한다.In one embodiment, the present invention provides a composition for controlling harmful algae comprising the compound represented by
본 발명의 유해조류 방제용 조성물은 공지의 방법에 따라 다양한 형태로 제조할 수 있으며, 효과를 저해하지 않는 범위 내에서 효과의 안정적 발현, 적용 대상 생물로의 부착 증진, 운반 및 처리의 간편화를 위해 제제학적으로 허용 가능한 고체 담체, 액체 담체,액체 희석제, 액화된 기체 희석제, 고체 희석제, 또는 기타 적당한 보조제, 예를 들면 유화제, 분산제 또는 기포제 등의 계면활성제를 더욱 포함할 수 있다.The composition for controlling harmful birds of the present invention can be prepared in various forms according to known methods. In order to stably express the effect within a range that does not inhibit the effect, to improve adhesion to the target organism, and to simplify transportation and treatment It may further comprise a surfactant such as a pharmaceutically acceptable solid carrier, a liquid carrier, a liquid diluent, a liquefied gas diluent, a solid diluent, or other suitable adjuvant such as an emulsifying agent, a dispersing agent or a foaming agent.
본 발명의 방제용 조성물은 바람직하게는 유제, 수화제, 입제, 분제, 캅셀형 및 젤상의 제형으로 제제화될 수있고, 제제의 부력을 위해 접촉제로서 제공되는 것이 바람직하다.The controlling composition of the present invention can be preferably formulated into emulsions, wettable powders, granules, powders, capsules and gels, and is preferably provided as a contact agent for buoyancy of the formulation.
나아가, 다른 구체예로서 본 발명은 상기 화학식 1로 표시되는 화합물 또는 그의 염을 유해조류가 발생한 지역 또는 발생예상 지역에 처리하는 것을 포함하는 유해조류의 제어(방제)방법을 제공한다. Further, as another embodiment, the present invention provides a method for controlling harmful algae comprising treating the compound represented by the above formula (1) or a salt thereof in a region where a harmful alga is generated or a region expected to occur.
예를 들어, 상기 조성물을 분말형태, 또는 고농도의 액상형태로 장기보존 및 상품화하여, 녹조가 발생한 지역 또는 징후가 보이는 곳에 선박을 이용하여 국부적으로 살포하는 형태로 수일에서 1주일 이내에 간단하게 녹조를 제어하고 예방할 수 있다. For example, the composition may be stored in powder form or in a liquid form at a high concentration for a long period of time and commoditized so that the green algae can be easily sprayed within a few days to one week in a form in which the algae are generated or sprayed locally, Control and prevent.
이 때, 본 발명의 상기 화학식 1로 표시되는 화합물 또는 그의 염을 방제지역에 처리할 경우, 처리 지역의 최종 농도를 기준으로 0.001uM 내지 10uM의 범위로 사용할 수 있으며, 바람직하게는 0.001uM 내지 5uM의 범위로 사용할 수 있다. 본 기술은 10,000 ton 규모의 저수지에서 담수산 유해조류가 5 × 105 cells/ mL 수준으로 발생했을 경우 분자량 300 Da의 녹조제어제가 200 nM에서 99%이상의 조류를 제거할 수 있다면 약 600 g의 분말을 현장수와 혼합하여 녹조가 발생한 수층에 골고루 살포해 준다면 수일 또는 1주일 이내에 조류해제 수준(∼ 500 cells/ mL)까지 녹조를 제어할 수 있다.At this time, when the compound of the present invention represented by the above formula (1) or its salt is treated in the control area, it can be used in the range of 0.001 uM to 10 uM based on the final concentration of the treatment area, preferably 0.001 uM to 5 uM Of the total. If the algal bacterium has a concentration of 5 × 10 5 cells / mL in a 10,000 ton reservoir, if the algal control agent with molecular weight of 300 Da can remove more than 99% of the algae at 200 nM, The green algae can be controlled to a level of algae release (~ 500 cells / mL) within a few days or a week if the algae are mixed evenly with the field water.
이때, 상기 조성물을 유해조류가 발생되는 초기에 처리함으로써 대량증식을 사전에 차단하는 것이 바람직하다.
At this time, it is preferable to block the mass proliferation in advance by treating the composition in the early stage of generation of harmful algae.
이처럼, 본 발명은 중. 소규모 수계의 복원 및 보존관리에 적용 가능한 기술(녹조제어 또는 예방)로서 인공양식장, 골프장, 공원, 유원지, 오락시설 내 연못, 저수지, 호수, 하천, 전국에 산재되어 있는 농업용저수지 등에 적용하여 녹조의 피해를 예방하고 유해조류를 제어함으로서 기타 인위적인 환경오염을 발생시키지 않는다. 그리고, 선박, 부두시설, 수영장, 건물 등에 사용되는 항조류 도료(antifouling paint)의 주요성분으로 사용가능하여 유독한 기존의 항도료를 대체하고 부착조류에 의한 미관손상, 내구력 저하, 성능저하 등을 예방할 수도 있다.As such, It is applicable to artificial aquaculture farms, golf courses, parks, amusement parks, ponds in amusement facilities, reservoirs, lakes, rivers, and agricultural reservoirs scattered all over the country as technologies applicable to the restoration and preservation management of small- Preventing damage and controlling harmful algae does not cause other anthropogenic environmental pollution. And it can be used as a main component of antifouling paint used in ships, wharf facilities, swimming pools, buildings, etc., thereby replacing existing toxic paint and reducing the appearance damage, durability, It can also be prevented.
또한, 먹는물, 농업용수, 공업용수 확보를 위한 수처리시설(상수처리, 하수처리)의 전처리 기술로서 적용되어 여과지 폐색, 독성물질의 과다노출을 예방하여 경제적 부담을 줄이고 먹는 물의 안전성을 확보할 수 있다. In addition, it is applied as a pretreatment technology of water treatment facility (water treatment, sewage treatment) for securing drinking water, agricultural water and industrial water, so that it can prevent excessive exposure of filter paper and toxic substances, have.
뿐만 아니라, 상대적으로 대규모 수계인 호소(댐), 상수원 및 하수 등 수계의 수질 개선, 환경기술 개발 등에 적용될 수 있다. 따라서, 농업용수의 개선 효과로 인해 우수 농산물 생산이 가능하고 식수의 안정화를 통해 국민건강에 이바지하여 개선 효과를 볼 수 있을 것이다. 또한, 중국처럼 심각한 녹조문제에 봉착해 있거나 태국같이 부착조류에 의한 방오도료의 수요가 큰 국가에 환경기술의 수출과 기술이전 등을 통한 고부가가치 창출과 국가이미지 재고, 국가 경쟁력 강화에 이바지 할 수 있다. 마지막으로 기술발전의 여하에 따라 연안에서 발생하는 적조제어에도 적극 활용가능하다.
In addition, it can be applied to the improvement of water quality in a relatively large scale water system, such as a lake, a water source, and sewage, and development of environmental technology. Therefore, it will be possible to produce excellent agricultural products due to the improvement effect of agricultural water and to contribute to the public health through stabilization of drinking water, and to see improvement effect. In addition, it can contribute to the creation of high value-added through the export of environment technology and the transfer of technology to the countries where there is a serious green tide problem like China, have. Finally, according to the technological development, it can be utilized for the control of the red tide occurring in the coast.
[실시예][Example]
이하, 본 발명을 실시예에 의해 상세히 설명하기로 한다. 그러나 이들 실시예는 본 발명을 보다 구체적으로 설명하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 한정되는 것은 아니다.Hereinafter, the present invention will be described in detail with reference to examples. However, these examples are intended to further illustrate the present invention, and the scope of the present invention is not limited to these examples.
먼저, 01-a부터 49-p까지 신규 115종의 화합물을 합성하여 1 μM에서 대조구(조류경보수준) 대비 녹조 유발종의 개체수를 90∼100% 이상 제어할 수 있는 다수의 화합물을 선별 분리하고, 미국 EPA 기준에 의거하여 생태독성 및 pilot (미소생태계, 유사현장생태계) 적용을 통한 위해성 평가를 수행하였다.
First, 115 kinds of compounds from 01-a to 49-p were synthesized, and a large number of compounds capable of controlling 90-100% or more of the population of green algae-induced species at 1 μM compared to the control (algal alert level) , Ecotoxicity and pilot (micro ecosystem, pseudo-field ecosystem) were applied according to US EPA standards.
실시예Example 1: 본 발명에 따른 유도체의 제조 1: Preparation of derivatives according to the present invention
본 발명의 나프토퀴논 유도체들을 다음과 같은 방법으로 제조하였다. 하기 모든 신규 화합물들의 기본 구조골격은 도 1을 기반으로 한다.
The naphthoquinone derivatives of the present invention were prepared by the following method. The basic framework of all the novel compounds below is based on Fig.
1-1 NQ01 -1. N-(1,3- Benzothiazol -2- yl )-N-[(1,4,5,8- tetramethoxy -2-naphthyl)methylidene]amine 1-1 NQ01 -1. N- (1,3- Benzothiazol -2- yl ) -N - [(1,4,5,8- tetramethoxy -2- naphthyl) methylidene] amine
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-aminobenzothiazole (1.21 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), 및 아세트산(300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 2.70 g을 수득하였다(Yield: 91.3%).20 mL of benzene, 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol) and 2-aminobenzothiazole (1.21 g, 7.25 mmol) were added to 100 mL of a round flask equipped with a Dean- 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), and acetic acid (300 [mu] L, pH 4-5) were added and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature, the reaction mixture was washed successively with 5% HCl, saturated NaHCO3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and hexane to give 2.70 g (Yield: 91.3%).
M.p: 161- 162℃M.p .: 161-162 ° C
1H NMR(300 MHz, CDCl3) δ 9.48 (1H, s), 8.02 (1H, d, J=8.1Hz), 7.85 (1H, d, J=7.9Hz), 7.68 (1H, s), 7.47 (1H, m), 7.38 (1H, m), 7.04 (1H, d, J=8.7Hz), 6.94 (1H, J=8.7Hz), 4.06 (3H, s), 4.01 (3H, s), 3.94 (3H, s)
D, J = 7.9 Hz), 7.68 (1H, s), 7.47 (1H, s), 8.04 (1H, (m, 2H), 7.38 (1H, m), 7.04 (1H, d, J = 8.7Hz), 6.94 , s)
1-2 NQ01 -2A. N-(1,3- Benzothiazol -2- yl )-N-[(1,4,5,8- tetramethoxy -2-naphthyl)methyl]amine 1-2 NQ01 -2A . N- (1,3- Benzothiazol -2- yl ) -N - [(1,4,5,8- tetramethoxy -2- naphthyl) methyl] amine
상온에서 tetrahydrofuran 30mL 중 교반된 용액인 N-(1,3-Benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl) methylidene] amine (2 g, 4.90 mmol) 에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 washed with water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 1.75 g을 수득하였다 (Yield: 87.3%).
To a stirred solution of 3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methylidene] amine (2 g, 4.90 mmol) in 30 mL of tetrahydrofuran at room temperature ) Was slowly added LiAlH 4 (195.7 mg, 4.90 mmol) over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with washed water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to give 1.75 g (Yield: 87.3%).
*M.p: 160℃* M.p: 160 ° C
1H NMR (200 MHz, CDCl3) δ 7.55(1H, d, J=7.8Hz), 7.46(1H, d, J=8.2), 7.23(1H, t, J=8.0Hz), 7.09(1H, t, J=7.4Hz), 6.96 (1H, s), 6.83 (2H, s), 4.83 (2H, s), 3.96 (3H, s), 3.88 (3H, s), 3.82 (6H, s)
T, J = 8.0 Hz), 7.09 (1H, t, J = 7.8 Hz), 7.46 (1H, (2H, s), 3.96 (3H, s), 3.88 (3H, s), 3.82
1-3 NQ01 -4. 6-{[(1,3- Benzothiazol -2- yl ) amino ] methyl }-5,8- dimethoxy -1,4-dihydro-1,4-naphthalenedione 1-3 NQ01 -4. 6 - {[(1,3- Benzothiazol -2- yl) amino] methyl} -5,8- dimethoxy - 1,4-dihydro-1,4-naphthalenedione
상온에서 acetone (20 mL) 중 교반된 용액 N-(1,3-Benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine (800 mg, 1.95 mmol)에 H2SO4 160 μl, H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔 상(ethyl acetate :n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 62% (459.7 mg)(1, 4-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine (800 mg, 1.95 mmol), 160 μl of H 2 SO 4 , 4 mL of H 2 O, and 203.2 mg (1.95 mmol) of CrO 3 were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 62% (459.7 mg)
M.p: 154 - 160℃.M.p .: 154 - 160 캜.
1H NMR (300 MHz, DMSO) δ 8.58 (1H, s), 7.69 (1H, d, J=8.0Hz), 7.63 (1H, s), 7.40 (1H, d, J=7.6Hz), 7.23 (1H, t, J=7.2Hz), 7.04 (1H, t, J=6.6Hz), 6.83 (2H, s), 4.73 (2H, s), 3.84 (3H, s), 3.81 (3H, s).
(1H, d, J = 7.6 Hz), 7.23 (1H, s), 7.63 t, J = 7.2 Hz), 7.04 (1H, t, J = 6.6 Hz), 6.83 (2H, s), 4.73 (2H, s), 3.84 (3H, s), 3.81 (3H, s).
1-4 NQ01 -3. 2-{[(1,3- Benzothiazol -2- yl ) amino ] methyl }-5,8- dimethoxy -1,4-dihydro-1,4-naphthalenedione 1-4 NQ01 -3. 2 - {[(1,3- Benzothiazol -2- yl) amino] methyl} -5,8- dimethoxy - 1,4-dihydro-1,4-naphthalenedione
5℃에서 acetonitrile (15 mL) 중 교반된 용액 N-(1,3-Benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine (800 mg, 2 mmol)에 3.5mL Lofwater 중 ammonium cerium(IV) nitrate (2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔상(ethyl acetate :n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 72% (533 mg).2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine (800 mg, 0.25 mmol) in acetonitrile , 2 mmol) was added a solution of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in 3.5 mL Lofwater. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 72% (533 mg).
M.p: 95 - 97℃M.p .: 95-97 ° C
1H NMR (300 MHz, DMSO) δ 8.40 (1H, t, J=7.5Hz), 7.69 (1H, d, J=7.3Hz), 7.53 (2H, s), 7.39 (1H, d, J=8.0Hz), 7.21 (1H, t, J=8.0Hz), 7.04 (1H, t, J=7.9Hz), 6.58 (1H, s), 4.46 (2H, d, J=5.7Hz), 3.87 (3H, s)p
D, J = 7.5 Hz), 7.69 (1H, d, J = 7.3 Hz), 7.53 (2H, s), 7.39 ), 7.21 (1H, t, J = 8.0 Hz), 7.04 (1H, t, J = 7.9 Hz), 6.58 (1H, s), 4.46 ) p
1-5 NQ01 -6A. 6-( Benzothiazol -2- ylaminomethyl )-5,8- dihydroxy -[1,4]naphthoquinone 1-5 NQ01 -6A. 6- (Benzothiazol -2- ylaminomethyl) -5,8- dihydroxy - [1,4] naphthoquinone
0~5℃에서 dry methylene chloride 40 mL 중 교반된 6-{[(1,3-Benzothiazol-2-yl)amino]methyl}-5,8-dimethoxy-1,4-dihydro-1,4- naphthalenedione (456.5 mg, 1.2 mmol)에 AlCl3 (1.61 g, 11.9 mmol)를 천천히 첨가하였다. 혼합물을 2시간 동안 교반하였다. 교반된 차가운 용액 10% HCl (500 mL)에 반응 혼합물 및 ethyl ether (500 mL)을 천천히 첨가하였다. 혼합물을 ethyl ether로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 255.5 mg을 수득하였다(Yield: 56.7%).Amino] methyl} -5,8-dimethoxy-1,4-dihydro-1,4-naphthalenedione in 40 mL of dry methylene chloride at 0-5 ° C was added to a stirred solution of 6 - {[(1,3-benzothiazol- (456.5 mg, 1.2 mmol) was slowly added AlCl 3 (1.61 g, 11.9 mmol). The mixture was stirred for 2 hours. To the stirred cold solution 10% HCl (500 mL) was slowly added the reaction mixture and ethyl ether (500 mL). The mixture was extracted with ethyl ether and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to give 255.5 mg (Yield: 56.7%).
1H NMR (300 MHz, DMSO) δ 7.6 (1H, d, J=11Hz), 7.45 (1H, d, J=10.7Hz), 7.4 (1H, s), 7.2 (2H, d, J=7.3Hz), 7.0 (1H, s), 4.8 (2H, d, J=5Hz), 2.6 (1H, s), 2.4 (1H, s).
(1H, d, J = 7.3 Hz), 7.45 (1H, d, J = 10.7 Hz), 7.4 (1H, s), 7.2 , 7.0 (1H, s), 4.8 (2H, d, J = 5 Hz), 2.6 (1H, s), 2.4 (1H, s).
1-6 NQ02 -1. N-(4- Methyl -1,3- benzothiazol -2- yl )-N-[(1,4,5,8-tetramethoxy-2-naphthy)methyliden]amine 1-6 NQ02 -1. N- (4- Methyl -1,3- benzothiazol -2- yl ) -N - [(1,4,5,8- tetramethoxy-2-naphthyl) methylidene] amine
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 200 mL에 벤젠 50 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (5 g, 18.1 mmol), 2-amino-4-methylbenzothiazole (3.04 g, 18.1 mmol), triethylamine (2.53 mL, 18.1 mmol), acetic acid (800 μl, 14 mmol)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 6.7 g (Yield: 87.5%)을 수득하였다50 mL of benzene, 2-formyl-1,4,5,8-tetramethoxynaphthalene (5 g, 18.1 mmol), and 2-amino-4-methylbenzothiazole were added to 200 mL of a round flask equipped with a Dean- (3.04 g, 18.1 mmol), triethylamine (2.53 mL, 18.1 mmol), acetic acid (800 μl, 14 mmol) and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature and washed, and then the reaction mixture is continuously 5% HCL, saturated NaHCO 3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and hexane to give 6.7 g (Yield: 87.5%)
M.p: 125 - 126℃M.p .: 125 - 126 캜
1H NMR (300 MHz, CDCl3) δ 9.45 (1H, s), 7.68 (1H, s), 7.65 (1H, m), 7.27 (2H, d, J=8.7Hz), 6.92 (1H, d, J=8.7Hz), 4.05 (3H, s), 3.99 (3H, s), 3.92 (3H, s), 3.91 (3H, s), 2.78 (3H, s).
D, J = 8.7 Hz), 6.92 (1H, s), 7.65 (1H, s), 7.65 8.7 Hz), 4.05 (3H, s), 3.99 (3H, s), 3.92 (3H, s), 3.91 (3H, s), 2.78 (3H, s).
1-7 NQ02 -2A. N-(4- Methyl -1,3- benzothiazol -2- yl )-N-[(1,4,5,8-tetramethoxy-2-naphthy)methyl]amine 1-7 NQ02-2A . N- (4- Methyl -1,3- benzothiazol -2- yl ) -N - [(1,4,5,8- tetramethoxy-2-naphthyl) methyl] amine
상온에서 tetrahydrofuran 50mL 중 교반된 용액인 N-(4-Methyl-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2- naphthy)methyliden] amine (6.5 g, 15.4 mmol)에 LiAlH4 (614.6 mg, 15.4 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 6.46 g (Yield: 98.9%)을 수득하였다.(4-Methyl-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methylidene] amine g, 15.4 mmol) was slowly added LiAlH 4 (614.6 mg, 15.4 mmol) over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to obtain 6.46 g (Yield: 98.9%).
M.p: 69 - 71℃M.p .: 69 - 71 ° C
1H NMR (300 MHz, CDCl3) δ 7.41(1H, d, J=7.7Hz), 7.10 (1H, d, J=7.4Hz), 6.98 (2H, m), 6.88 (1H, d, J=8.8Hz), 6.81 (1H, d, J=8.8Hz), 6.02 (1H, s), 4.80 (2H, s), 3.96 (3H, s), 3.89 (6H, s), 3.83 (3H, s), 2.59 (3H, s).
(2H, m), 6.88 (1H, d, J = 8.8Hz, 1H), 7.41 (1H, d, J = 7.7Hz) ), 6.81 (1H, d, J = 8.8 Hz), 6.02 (1H, s), 4.80 (2H, s), 3.96 (3H, s), 3.89 (3H, s).
1-8 NQ02 -4. 6-{[(4- Methyl -1,3- benzothiazol -2- yl ) amino ] methyl }-5,8-dimethoxy-1,4--dihydro-1,4-naphthalenedione 1-8 NQ02 -4. 6 - {[(4- methyl -1,3- benzothiazol -2- yl ) amino ] methyl } -5,8- dimethoxy- 1,4-dihydro-1,4-naphthalenedione
상온에서 acetone (10 mL) 중 교반된 용액 N-(4-Methyl-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthy) methyl] amine (827.4 mg, 1.95 mmol)에 H2SO4 250 μl, H2O 770 μl, CrO3 300 mg (3 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔 상(ethyl acetate :n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 90.5% (659.8mg)
(4-Methyl-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine (827.4 mg, 1.95 mmol), 250 μl of H 2 SO 4 , 770 μl of H 2 O and 300 mg (3 mmol) of CrO 3 were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 90.5% (659.8 mg)
M.p: 133 - 134℃M.p .: 133 - 134 캜
1H NMR (300 MHz, CDCl3) δ 7.54 (1H, s), 7.40 (1H, d, J=7.8Hz), 7.11 (1H, d, J=7.3Hz), 7.00 (1H, t, J=7.6Hz), 6.75 (2H, s), 6.14 (1H, broad), 4.77 (2H, s), 3.92 (3H, s), 3.90 (3H, s), 2.56 (3H, s).
(1H, d, J = 7.8 Hz), 7.11 (1H, d, J = 7.3 Hz), 7.00 ), 6.75 (2H, s), 6.14 (1H, broad), 4.77 (2H, s), 3.92 (3H, s), 3.90 (3H, s), 2.56 (3H, s).
1-9 NQ02 -3. 2-{[(4- Methyl -1,3- benzothiazol -2- yl ) amino ] methyl }-5,8-dimethoxy-1,4--dihydro-1,4-naphthalenedione
1-9 NQ02 -3. 2 - {[(4- methyl -1,3- benzothiazol -2- yl ) amino ] methyl } -5,8- dimethoxy- 1,4-dihydro-1,4-naphthalenedione
5℃에서 acetonitrile (15 mL) 중 교반된 용액 N-(4-Methyl-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthy) methyl] amine (827.4 mg, 2 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate 3.29 g, 5.7 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔상(ethyl acetate :n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 82.3% (632.8 mg)
Methyl-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methyl] piperazine in acetonitrile (15 mL) amine (827.4 mg, 2 mmol) was added a solution of ammonium cerium (IV) nitrate (3.29 g, 5.7 mmol) in 3.5 mL water. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 82.3% (632.8 mg)
M.p: 151 - 153℃.M.p .: 151-153 ° C.
1H NMR (300 MHz, CDCl3) δ 7.39(1H, d, J=7.8Hz), 7.30(2H, s), 7,09(1H, d, J=7.3Hz), 6.98(1H, t, J=7.7Hz), 6.87(1H, s), 5.87(1H, broad), 4.55(2H, s), 3.97(3H, s), 3.93(3H, s), 2.53(3H, s).
(1H, d, J = 7.8 Hz), 7.30 (2H, s), 7.09 3H, s), 2.53 (3H, s), 3.87 (3H, s), 3.87 (2H, s).
1-10 NQ02 -5. 5,8- Dihydroxy -2-[(4- methyl - benzothiazol -2- ylamino )-methyl]-[1,4]naphthoquinone 1-10 NQ02 -5. 5,8- Dihydroxy- 2 - [(4- methyl - benzothiazol -2- ylamino ) -methyl ] - [1,4] naphthoquinone
0~5℃에서 dry methylene chloride 40 mL 중 교반된 2-{[(4-Methyl-1,3-benzothiazol-2-yl)amino]methyl}-5,8-dimethoxy-1,4--dihydro-1,4- naphthalenedione (473.3 mg, 1.2 mmol)에 AlCl3 (1.61 g, 11.9 mmol)를 천천히 첨가하였다. 혼합물을 2시간 동안 교반하였다. 교반된 차가운 용액 10% HCl (500 mL)에 반응 혼합물 및 ethyl ether (500 mL)을 천천히 첨가하였다. 혼합물을 ethyl ether로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 240 mg (Yield: 50.7%)을 수득하였다.2-yl) amino] methyl} -5,8-dimethoxy-1,4-dihydro-benzoic acid in 40 mL of dry methylene chloride at 0 ~ AlCl 3 (1.61 g, 11.9 mmol) was slowly added to 1,4-naphthalenedione (473.3 mg, 1.2 mmol). The mixture was stirred for 2 hours. To the stirred cold solution 10% HCl (500 mL) was slowly added the reaction mixture and ethyl ether (500 mL). The mixture was extracted with ethyl ether and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to give 240 mg (Yield: 50.7%).
1H NMR (300 MHz, DMSO) δ 8.5 (1H, s), 7.6 (1H, d, J=8.7Hz), 7.4 (1H, s), 7.25 (1H, d, J=9.3Hz), 7.1 (1H, s), 7.0 (1H, d, J=8.3Hz), 4.6 (2H, d, J=6.0Hz), 2.4 (2H, s), 1.2 (3H, s).
(1H, s), 7.25 (1H, d, J = 9.3 Hz), 7.1 (1H, s), 7.6 (2H, s), 7.0 (1H, d, J = 8.3Hz), 4.6 (2H, d, J = 6.0Hz), 2.4 (2H, s), 1.2 (3H, s).
1-11 NQ03 -1. N-(5,6- Dimethyl -1,3- benzothiazol -2- yl )-N-[(1,4,5,8-tetramethoxy-2-naphthyl)methylidene]amine 1-11 NQ03 -1. N- (5,6- Dimethyl -1,3- benzothiazol -2- yl ) -N - [(1,4,5,8- tetramethoxy-2-naphthyl) methylidene] amine
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-5,6-dimethyl benzothiazole (1.29 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 2.58 g (Yield: 81.7%)을 수득하였다.20 mL of benzene, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-5,6-dihydro- (1.29 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μL, pH 4-5) was added and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature and washed, and then the reaction mixture is continuously 5% HCL, saturated NaHCO 3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and hexane to give 2.58 g (Yield: 81.7%).
M.p: 162 - 169℃.M.p .: 162-169 ° C.
1H NMR (300 MHz, CDCl3) δ 9.42(1H, s), 7.77 (1H, s), 7.76 (1H, s), 7.57 (1H, s), 7.01 (1H, d, J=8.8Hz), 6.91 (1H, d, J=8.8Hz), 4.04 (3H, s), 3.99 (3H, s), 3.92 (3H, s), 3.90 (3H, s), 2.39 (3H, s), 2.38 (3H, s).
(1H, s), 7.76 (1H, s), 7.57 (1H, s), 7.01 (1H, d, J = 8.8Hz), 6.91 (3H, s), 3.39 (3H, s), 3.92 (3H, s), 3.90 s).
1-12 NQ03 -2A. N-(5,6- Dimethyl -1,3- benzothiazol -2- yl )-N-[(1,4,5,8-tetramethoxy-2-naphthyl)methyl]amine 1-12 NQ03-2A . N- (5,6- Dimethyl -1,3- benzothiazol -2- yl ) -N - [(1,4,5,8- tetramethoxy-2-naphthyl) methyl] amine
상온에서 tetrahydrofuran 30mL 중 교반된 용액인 N-(5,6-Dimethyl-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2- naphthyl) methylidene] amine (2.14 g, 4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 2.1 g (Yield: 97.7%)을 수득하였다(5,6-Dimethyl-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methylidene] amine (2.14 g, 4.90 mmol) was slowly added LiAlH 4 (195.7 mg, 4.90 mmol) over 10 min. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to obtain 2.1 g (Yield: 97.7%)
M.p: 173 - 174℃M.p .: 173-174 ° C
1H NMR (200 MHz, CDCl3) 8.36(1H, t, J=5.5Hz), 7.45(1H, s), 7.26(1H, s), 7.09(1H, s), 6.98(1H, d, J=8.7Hz), 6.91(1H, d, J=8.7Hz), 4.75(2H, d, J=5.5Hz), 3.90(3H, s), 3.80 (6H, s), 3.76 (3H, s), 2.27 (3H, s), 2.26 (3H, s).
(1H, s), 6.98 (1H, d, J = 8.7 (1H, s) 3H, s), 3.76 (3H, s), 2.27 (2H, d, J = 3H, s), 2.26 (3H, s).
1-13 NQ03 -4. 6-{[(5,6- Dimethyl -1,3- benzothiazol -2- yl ) amino ] methyl }-5,8-dimethoxy-1,4-dihydro-1,4-naphthalendione 1-13 NQ03 -4. 6 - {[(5,6- Dimethyl -1,3- benzothiazol -2- yl ) amino ] methyl } -5,8-dimethoxy- 1,4-dihydro-1,4-naphthalendione
상온에서 acetone (20 mL) 중 교반된 용액 N-(5,6-Dimethyl-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl )methyl]amine (854.6 mg, 1.95 mmol)에 H2SO4 160 μl, H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔 상(ethyl acetate :n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 86.9% (691.8 mg)To a stirred solution of acetone (20 mL) at room temperature was added a solution of N- (5,6-Dimethyl-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methyl ] amine (854.6 mg, 1.95 mmol), 160 μl of H 2 SO 4 , 4 mL of H 2 O and 203.2 mg (1.95 mmol) of CrO 3 were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 86.9% (691.8 mg)
M.p: 135 - 137℃M.p .: 135-137 DEG C
1H NMR (200 MHz, DMSO) δ 8.40 (1H, t, J=5.6Hz), 7.60 (1H, s), 7.41 (1H, s), 7.20 (1H, s), 6.82 (2H, s), 4.68 (2H, d, J=5.6Hz), 3.81 (3H, s), 3.79 (3H, s), 2.21 (6H, s).
S), 7.20 (1H, s), 6.82 (2H, s), 4.68 (1H, s) (2H, d, J = 5.6 Hz), 3.81 (3H, s), 3.79 (3H, s), 2.21 (6H, s).
1-14 NQ03 -3. 2-{[(5,6- Dimethyl -1,3- benzothiazol -2- yl ) amino ] methyl }-5,8-dimethoxy-1,4-dihydro-1,4-naphthalendione 1-14 NQ03 -3. 2 - {[(5,6- Dimethyl -1,3- benzothiazol -2- yl ) amino ] methyl } -5,8- dimethoxy- 1,4-dihydro-1,4-naphthalendione
5℃에서 acetonitrile (15 mL) 중 교반된 용액 N-(5,6-Dimethyl-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl) methyl]amine (854.6 mg, 2 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔상(ethyl acetate :n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 73.2% (582.7 mg)(5,6-Dimethyl-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine (854.6 mg, 2 mmol) was added a solution of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in 3.5 mL water. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 73.2% (582.7 mg)
M.p: 129 - 130℃M.p .: 129 - 130 캜
1H NMR (200 MHz, DMSO) δ 8.23 (1H, s), 7.52 (2H, s), 7.40 (1H, s), 7.18 (1H, s), 6.55 (1H, s), 4.41 (2H, s), 3.86 (3H, s), 3.82 (3H, s), 2.19 (6H, s)
(2H, s), 7.51 (1H, s), 7.40 (1H, s), 7.18 (1H, s) , 3.86 (3H, s), 3.82 (3H, s), 2.19 (6H, s)
*1-15 NQ04 -1. 4- chloro -N-((1,4,5,8- tetramethoxynaphthalene -2-yl)methylene)benzothiazol-2-amine* 1-15 NQ04 -1. 4- chloro -N - ((1,4,5,8- tetramethoxynaphthalene -2- yl) methylene) benzothiazol-2-amine
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-4-chlorobenzothiazole (1.34 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 2.2 g (Yield: 69 %)을 수득하였다.20 mL of 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol) and 2-Amino-4-chlorobenzothiazole (20 mL) were added to 100 mL of a round flask equipped with a Dean- (1.34 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5) and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature and washed, and then the reaction mixture is continuously 5% HCL, saturated NaHCO 3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and hexane to give 2.2 g (Yield: 69%).
1H NMR (300 MHz, DMSO) δ 9.43 (1H, s), 7.74 (1H, dd, J=8.0 and 1.0Hz), 7.65 (1H, s), 7.49 (1H, dd, J=7.8 and 1.0Hz), 7.04 (1H, t, J=7.9Hz), 7.03 (1H, d, J=8.7Hz), 6.94 (1H, d, J=8.7Hz), 4.04 (3H, s), 4.00 (3H, s), 3.93 (3H, s), 3.92 (3H, s)
Dd, J = 8.0 and 1.0 Hz), 7.65 (1H, s), 7.49 (1H, dd, J = 7.8 and 1.0 Hz). 1H NMR (300 MHz, DMSO)? 9.43 , 7.04 (1H, t, J = 7.9 Hz), 7.03 (1H, d, J = 8.7 Hz), 6.94 (1H, d, J = 8.7 Hz), 4.04 (3H, , 3.93 (3 H, s), 3.92 (3 H, s)
1-16 NQ04 -2A. 4- chloro -N-((1,4,5,8- tetramethoxynaphthalene -2-yl)methyl)benzothiazol-2-amine 1-16 NQ04-2A . 4- chloro -N - ((1,4,5,8- tetramethoxynaphthalene -2- yl) methyl) benzothiazol-2-amine
상온에서 tetrahydrofuran 30mL 중 교반된 용액인 4-chloro-N-((1,4,5,8-tetramethoxynaphthalene-2-yl)methylene) benzothiazol-2-amine (2.17 g, 4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 Diethyl ether로부터 재결정하여 1.93 g (Yield: 89%)을 수득하였다.To a stirred solution of 4-chloro-N - ((1,4,5,8-tetramethoxynaphthalene-2-yl) methylene) benzothiazol-2-amine (2.17 g, 4.90 mmol) in 30 mL of tetrahydrofuran at room temperature was added LiAlH 4 mg, 4.90 mmol) was slowly added over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from diethyl ether to give 1.93 g (Yield: 89%).
1H NMR (300 MHz, DMSO) δ 7.43 (1H, dd, J=7.8 and 0.6Hz), 7.29 (1H, dd, J=8.0 and 0.6Hz), 7.18 (1H, s), 6.96 (1H, t, J=8.2Hz), 6.96 (1H, s), 6.82 (2H, s), 4.70 (2H, d, J=5.8Hz), 3.94 (3H, s), 3.86 (3H, s), 3.80 (3H, s), 3.78 (3H, s)
Dd, J = 8.0 and 0.6 Hz), 7.18 (1H, s), 6.96 (1H, t, J = 7.8 and 0.6 Hz) (3H, s), 3.80 (3H, s), 3.96 (2H, d, J = s), 3.78 (3 H, s)
1-17 NQ04 -4. 6-((4- chlorobenzothiazol -2- ylamino ) methyl -5-8-dimethoxynaphthalene-1,4-dione 1-17 NQ04 -4. 6 - ((4- chlorobenzothiazol -2- ylamino ) methyl -5-8- dimethoxynaphthalene-1,4-dione
상온에서 acetone (20 mL) 중 교반된 용액 4-chloro-N-((1,4,5,8-tetramethoxynaphthalene-2-yl)methyl) benzothiazol-2- amine 861.1 mg (1.95 mmol)에 H2SO4 164 μl (2.93 mmol), H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 acetone 및 ethyl ether로부터 재결정하여 수득하였다. Yield: 75% (600 mg).
A solution of 4-chloro-N stirred at room temperature acetone (20 mL) - a ((1,4,5,8-tetramethoxynaphthalene-2- yl) methyl) benzothiazol-2- amine 861.1 mg (1.95 mmol) H 2 SO 4 164 μl (2.93 mmol), H 2 O 4 mL, and CrO 3 203.2 mg (1.95 mmol) were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was obtained by recrystallization from acetone and ethyl ether. Yield: 75% (600 mg).
1H NMR (300 MHz, DMSO) δ 8.86 (1H, t, J=5.8Hz), 7.69 (1H, s), 7.66 (1H, d, J=7.8Hz), 7.30 (1H, d, J=7.8Hz), 7.00 (1H, t, J=8.0Hz), 6.81 (2H, s), 4.70 (2H, d, J=5.8Hz), 3.85 (3H, s), 3.82 (3H, s)
(1H, d, J = 7.8 Hz), 7.69 (1H, d, J = 7.8Hz) ), 7.00 (1H, t, J = 8.0 Hz), 6.81 (2H, s), 4.70 (2H, d, J = 5.8 Hz), 3.85
1-18 NQ04 -3. 2-((4- chlorobenzothiazol -2- ylamino ) methyl -5-8-dimethoxynaphthalene-1,4-dione 1-18 NQ04 -3. 2 - ((4- chlorobenzothiazol -2- ylamino ) methyl -5-8- dimethoxynaphthalene-1,4-dione
5℃에서 acetonitrile (15 mL) 중 교반된 용액 4-chloro-N-((1,4,5,8-tetramethoxynaphthalene-2-yl)methyl) benzothiazol-2- amine 861.1 mg (1.95 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 acetone 및 n-hexan로부터 재결정하였다.Yield: 61% (490 mg)
To a stirred solution of 4-chloro-N - ((1,4,5,8-tetramethoxynaphthalene-2-yl) methyl) benzothiazol-2- amine (861.1 mg, 1.95 mmol) in acetonitrile A solution of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in water was added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The result was recrystallized from acetone and n-hexane. Yield: 61% (490 mg)
1H NMR (300 MHz, DMSO) δ 8.64 (1H, t, J=6.0Hz), 7.66 (1H, d, J=7.7Hz), 7.55 (2H, s), 7.30 (1H, d, J=7.9Hz), 7.03 (1H, t, J=7.9Hz), 6.63 (1H, s), 4.47 (2H, d, J=6.0Hz), 3.85 (3H, s), 3.82 (3H, s).(2H, s), 7.30 (1H, d, J = 7.9Hz), 7.65 (1H, d, J = ), 7.03 (1H, t, J = 7.9Hz), 6.63 (1H, s), 4.47 (2H, d, J = 6.0Hz), 3.85 (3H, s), 3.82 (3H, s).
1-19 NQ05 -1. 6- chloro -N-((1,4,5,8-tetramethoxynaphthaleneyl)methylene)benzothiazol-2-amine 1-19 NQ05 -1. 6- chloro- N - ((1,4,5,8- tetramethoxynaphthalenyl) methylene) benzothiazol-2-amine
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-6-chlorobenzothiazole (1.34 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 2.96 g (Yield: 93 %)을 수득하였다.20 mL of 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol) and 2-Amino-6-chlorobenzothiazole were added to 100 mL of a round flask equipped with a Dean-Stark trap and a condenser. (1.34 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5) and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature and washed, and then the reaction mixture is continuously 5% HCL, saturated NaHCO 3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and hexane to give 2.96 g (Yield: 93%).
1H NMR (300 MHz, DMSO) δ 9.45 (1H, s), 7.90 (1H, d, J=8.8Hz), 7.81 (1H, d, J=2.0Hz), 7.63 (1H, s), 7.43 (1H, dd, J=8.6Hz and 2.0Hz), 7.04 (1H, d, J=8.7Hz), 6.94 (1H, d, J=8.7Hz), 4.04 (3H, s), 4.00 (3H, s), 3.93 (3H, s), 3.92 (3H, s)
D, J = 2.0 Hz), 7.63 (1H, s), 7.43 (1H, s), 7.90 dd, J = 8.6 Hz and 2.0 Hz), 7.04 (1H, d, J = 8.7 Hz), 6.94 (1H, d, J = 8.7 Hz), 4.04 (3H, 3.93 (3 H, s), 3.92 (3 H, s)
1-20 NQ05 -2A. 6- chloro -N-((1,4,5,8- tetramethoxynaphthalene - yl)methyl)benzothiazol-2-amine 1-20 NQ05-2A . 6- chloro- N - ((1,4,5,8- tetramethoxynaphthalene - yl) methyl) benzothiazol-2-amine
상온에서 tetrahydrofuran 30mL 중 교반된 용액인 6-chloro-N-((1,4,5,8-tetramethoxynaphthalene-2-yl)methylene) benzothiazol-2-amine (2.17 g, 4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 Diethyl ether로부터 재결정하여 2.03 g (Yield: 93.7%)을 수득하였다
To a stirred solution of 6-chloro-N - ((1,4,5,8-tetramethoxynaphthalene-2-yl) methylene) benzothiazol-2-amine (2.17 g, 4.90 mmol) in 30 mL of tetrahydrofuran at room temperature was added LiAlH 4 mg, 4.90 mmol) was slowly added over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from diethyl ether to give 2.03 g (yield: 93.7%) of
1H NMR (300 MHz, DMSO) δ 7.52 (1H, d, J=2.0Hz), 7.40 (1H, d, J=8.4Hz), 7.20 (1H, dd, J=8.4 and 2.0Hz), 6.91 (1H, s), 6.85 (2H, s), 6.18 (1H, s), 4.81 (2H, d, J=4.8), 3.96 (3H, s), 3.87 (3H, s), 3.87 (3H, s), 3.83 (3H, s)
(1H, d, J = 8.4 and 2.0 Hz), 6.91 (1H, d, J = 8.4 Hz) s), 3.87 (3H, s), 3.87 (3H, s), 6.85 (2H, 3.83 (3 H, s)
1-21 NQ05 -4. 6-((6- chlorobenzothiazol -2- ylamino ) methyl -5-8-dimethoxynaphthalene-1,4-dione 1-21 NQ05 -4. 6 - ((6- chlorobenzothiazol -2- ylamino ) methyl -5-8- dimethoxynaphthalene-1,4-dione
상온에서 acetone (20 mL) 중 교반된 용액 6-chloro-N-((1,4,5,8-tetramethoxynaphthalene-2-yl)methyl) benzothiazol-2- amine 861.1 mg (1.95 mmol)에 H2SO4 164 μl (2.93 mmol), H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 acetone 및 ethyl ether로부터 재결정하여 수득하였다. Yield: 71% (571.3 mg)
A solution of 6-chloro-N was stirred at room temperature acetone (20 mL) - a ((1,4,5,8-tetramethoxynaphthalene-2- yl) methyl) benzothiazol-2- amine 861.1 mg (1.95 mmol) H 2 SO 4 164 μl (2.93 mmol), H 2 O 4 mL, and CrO 3 203.2 mg (1.95 mmol) were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was obtained by recrystallization from acetone and ethyl ether. Yield: 71% (571.3 mg)
1H NMR (300 MHz, DMSO) δ 8.29 (1H, t, J=6.0Hz), 7.45 (1H, d, J=3.0Hz), 7.24 (1H, s), 7.02 (1H, d, J=9.0Hz), 6.88 (1H, dd, J=8.6Hz and 2.0Hz), 6.46 (2H, s), 4.35 (2H, d, J=6.0Hz), 3.46 (3H, s), 3.42 (3H, s)
J = 6.0 Hz), 7.45 (1H, d, J = 3.0 Hz), 7.24 (1H, s), 7.02 (1H, ), 6.88 (1H, dd, J = 8.6 Hz and 2.0 Hz), 6.46 (2H, s), 4.35
1-22 NQ05 -3. 2-((6- chlorobenzothiazol -2- ylamino ) methyl -5-8-dimethoxynaphthalene-1,4-dione 1-22 NQ05 -3. 2 - ((6- chlorobenzothiazol -2- ylamino ) methyl -5-8- dimethoxynaphthalene-1,4-dione
5℃에서 acetonitrile (15 mL) 중 교반된 용액 6-chloro-N-((1,4,5,8-tetramethoxynaphthalene-2-yl)methyl) benzothiazol-2- amine 861.1 mg (1.95 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 acetone 및 n-hexan로부터 재결정하였다.Yield: 61% (486.3 mg)
To a stirred solution of 6-chloro-N - ((1,4,5,8-tetramethoxynaphthalene-2-yl) methyl) benzothiazol-2- amine in acetonitrile (15 mL) at 5 ° C, 3.5 mL A solution of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in water was added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The result was recrystallized from acetone and n-hexane. Yield: 61% (486.3 mg)
1H NMR (300 MHz, DMSO) δ 8.53 (1H, t, J=6.8Hz), 7.81 (1H, d, J=2.4Hz), 7.55 (2H, s), 7.36 (1H, d, J=8.1Hz), 7.23 (1H, dd, J=6.9 and 1.8Hz), 6.56 (1H, s), 4.45 (2H, d, J=5.1Hz), 3.86 (3H, s), 3.82 (3H, s)
D, J = 6.8 Hz), 7.81 (1H, d, J = 2.4 Hz), 7.55 (2H, s), 7.36 ), 7.23 (1H, dd, J = 6.9 and 1.8 Hz), 6.56 (1H, s), 4.45 (2H, d, J = 5.1 Hz), 3.86 (3H, s), 3.82
1-23 NQ06 -1.(6- Methanesulfony - benzothiazol -2- yl )-(1,4,5,8- tetramethoxy -naphthalen-2-ylmethylene)-amine 1-23 NQ06 -1. (6- Methanesulfonyl - benzothiazol -2- yl ) - (1,4,5,8- tetramethoxy - naphthalen-2- ylmethylene) -amine
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-6-(methylsulfonyl) benzothiazole (1.65 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 3.3 g (Yield: 91.2%)을 수득하였다.20 mL of 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-amino-6- ( (1.65 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol) and acetic acid (300 μL, pH 4-5) were added and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature and washed, and then the reaction mixture is continuously 5% HCL, saturated NaHCO 3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and hexane to give 3.3 g (Yield: 91.2%).
1H-NMR (300Hz, CDCl3) δ 10.5(1H, s), 8.2 (1H, s), 7.9 (1H, d, J=9.6Hz), 6.9 (1H, d, J=9.6Hz), 4.0 (12H, s), 3.1 (3H, s)
D, J = 9.6 Hz), 4.0 (12H, s), 7.9 (1H, d, J = , < / RTI > s), 3.1 (3H, s)
1-24 NQ06 -2A. (6- Methanesulfony - benzothiazol -2- yl )-(1,4,5,8-tetramethoxy-naphthalen-2-ylmethyl)-amine 1-24 NQ06-2A . (6- Methanesulfonyl - benzothiazol -2- yl ) - (1,4,5,8- tetramethoxy-naphthalen-2-ylmethyl) -amine
상온에서 tetrahydrofuran 30mL 중 교반된 용액인 NQ06-1에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 2.1 g (Yield: 91.7%)을 수득하였다
The LiAlH 4 (195.7 mg, 4.90 mmol ) at room temperature in the the stirring of tetrahydrofuran 30mL solution NQ06-1 was added slowly over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to obtain 2.1 g (Yield: 91.7%)
1H-NMR (300Hz, CDCl3) δ 7.9(1H, s), 7.8 (2H, d, J=9.6Hz), 7.7 (1H, d, J=9.6Hz), 6.0 (1H, s), 4.0 (14H, s), 3.1 (3H, s)
(1H, s), 4.0 (14H, s), 7.7 (1H, s), 7.8 , < / RTI > s), 3.1 (3H, s)
1-25 NQ06 -4. 6-[(6- Methanesulfonyl - benzothiazol -2- ylamino )- methyl ]-5,8-dimethoxy-[1,4]naphthoquinone 1-25 NQ06 -4. 6 - [(6- Methanesulfonyl - benzothiazol -2- ylamino) - methyl] -5,8- dimethoxy- [1,4] naphthoquinone
상온에서 acetone (20 mL) 중 교반된 용액 NQ06-2A (925.7 mg, 1.95 mmol)에 H2SO4 160 μl, H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 acetone 및 dimethyl ether로부터 재결정하여 수득하였다. Yield: 63% (600.2 mg)160 μl of H 2 SO 4 , 4 mL of H 2 O and 203.2 mg (1.95 mmol) of CrO 3 were added to the stirred solution NQ06-2A (925.7 mg, 1.95 mmol) in acetone (20 mL) at room temperature. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The product was obtained by recrystallization from acetone and dimethyl ether. Yield: 63% (600.2 mg)
1H-NMR (300Hz, CDCl3) δ 7.9 (1H, s), 7.8 (2H, d, J=9.6Hz), 7.7 (1H, d, J=9.6Hz), 6.0 (1H, s), 4.6 (2H, s), 4.0 (6H, s), 3.1 (3H, s)
D, J = 9.6 Hz), 6.0 (1H, s), 4.6 (2H, s), 7.8 , s), 4.0 (6H, s), 3.1 (3H, s)
1-26 NQ06 -3. 2-[(6- Methanesulfonyl - benzothiazol -2- ylamino )- methyl ]-5,8-dimethoxy-[1,4]naphthoquinone 1-26 NQ06 -3. 2 - [(6- Methanesulfonyl - benzothiazol -2- ylamino) - methyl] -5,8- dimethoxy- [1,4] naphthoquinone
5℃에서 acetonitrile (15 mL) 중 교반된 용액 NQ06-2A (925.7 mg, 1.95 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 acetone 및 dimethyl ether로부터 재결정하였다. Yield: 59% (545 mg)To a stirred solution of NQ06-2A (925.7 mg, 1.95 mmol) in acetonitrile (15 mL) at 5 ° C was added ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in 3.5 mL water. The reaction was stirred at ambient temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from acetone and dimethyl ether. Yield: 59% (545 mg)
1H-NMR (300Hz, CDCl3) δ 7.9 (1H, s), 7.8 (2H, d, J=9.6Hz), 7.7 (1H, d, J=9.6Hz), 6.0 (1H, s), 4.0 (8H, s), 3.1 (3H, s)
(1H, s), 4.0 (1H, s), 7.8 (2H, d, J = , < / RTI > s), 3.1 (3H, s)
1-27 NQ07 -1. 5- methyl -N-((1,4,5,8- tetramethoxynaphthalen -2-yl)methylene)thiazol-2-amine-2-formyl-1,4,5,8-tetra methoxynaphthalene 1-27 NQ07 -1. 5- methyl -N - ((1,4,5,8- tetramethoxynaphthalen -2- yl) methylene) thiazol-2-amine-2-formyl-1,4,5,8-tetra methoxynaphthalene
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-5-methylthiazole (827.7 m g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 2.47 g (Yield: 91.2%)을 수득하였다.20 mL of 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol) and 2-Amino-5-methylthiazole were added to 100 mL of a round flask equipped with a Dean-Stark trap and a condenser. (827.7 mg, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μL, pH 4-5) and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature and washed, and then the reaction mixture is continuously 5% HCL, saturated NaHCO 3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and hexane to give 2.47 g (Yield: 91.2%).
1H NMR (300 MHz, DMSO) δ 9.28 (1H, s), 7.45 (1H, s), 7.38 (1H, s), 7.10 (2H, d, J=4.2Hz), 3.90 (3H, s), 3.88 (3H, s), 3.79 (3H, s), 3.76 (3H, s), 2.46 (3H, s)
(2H, d, J = 4.2 Hz), 3.90 (3H, s), 3.88 (1H, s), 7.38 (3H, s), 3.79 (3H, s), 3.76 (3H, s), 2.46
1-28 NQ07 -2A. 5- methyl -N-((1,4,5,8- tetramethoxynaphthalen -2-yl)methyl)thiazol-2-amine 1-28 NQ07-2A . 5- methyl -N - ((1,4,5,8- tetramethoxynaphthalen -2- yl) methyl) thiazol-2-amine
상온에서 tetrahydrofuran 30mL 중 교반된 용액인 5-methyl-N-((1,4,5,8-tetramethoxynaphthalen-2-yl)methylene)thiazol-2-amine 1.82 g (4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 1.69 g (Yield: 91.7%)을 수득하였다.To 1.82 g (4.90 mmol) of 5-methyl-N - ((1,4,5,8-tetramethoxynaphthalen-2- yl) methylene) thiazol-2-amine in 30 mL of tetrahydrofuran at room temperature was added LiAlH 4 , 4.90 mmol) was slowly added over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to give 1.69 g (Yield: 91.7%).
1H NMR (300 MHz, DMSO) δ 7.73 (1H, t, J=6.0Hz), 6.96 (1H, s), 6.92 (1H, d, J=9.0Hz), 6.85 (1H, d, J=9.0Hz), 6.65 (1H, s), 4.53 (2H, d, J=6.0Hz), 3.83 (3H, s), 3.74 (3H, s), 3.73 (3H, s), 3.65 (3H, s), 2.17 (3H, s)
(1H, d, J = 9.0Hz), 6.85 (1H, d, J = 9.0Hz) ), 6.65 (1H, s), 4.53 (2H, d, J = 6.0 Hz), 3.83 (3H, s), 3.74 (3H, s)
1-29 NQ07 -4. 5,8- dimethoxy -6-((5- methylthiazol -2-ylamino)methyl)naphthalene-1,4-dione 1-29 NQ07 -4. 5,8- dimethoxy- 6 - ((5- methylthiazol -2- ylamino) methyl) naphthalene-1,4-dione
상온에서 acetone (20 mL) 중 교반된 용액 5-methyl-N-((1,4,5,8-tetramethoxynaphthalen-2-yl)methyl)thiazol-2-amine 730.2 mg (1.95 mmol)에 H2SO4 160 μl, H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 acetone 및 dimethyl ether로부터 재결정하여 수득하였다. Yield: 63% (423.1 mg)A solution of 5-methyl-N was stirred at room temperature acetone (20 mL) - a ((1,4,5,8-tetramethoxynaphthalen-2- yl) methyl) thiazol-2-amine 730.2 mg (1.95 mmol) H 2 SO 4, 160 mL of H 2 O, and 203.2 mg (1.95 mmol) of CrO 3 were added thereto. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The product was obtained by recrystallization from acetone and dimethyl ether. Yield: 63% (423.1 mg)
1H NMR (300 MHz, DMSO) δ 7.83 (1H, t, J=6.0Hz), 7.57 (1H, s), 6.80 (2H, s), 6.65 (1H, s), 4.52 (2H, d, J=5.7Hz), 3.79 (3H, s), 3.73 (3H, s), 3.18 (3H, s)
(1H, s), 6.65 (1H, s), 4.52 (2H, d, J = 5.7 Hz), 3.79 (3H, s), 3.73 (3H, s), 3.18
1-30 NQ07 -3. 5,8- dimethoxy -2-((5- methylthiazol -2-ylamino)methyl)naphthalene-1,4-dione 1-30 NQ07 -3. 5,8- dimethoxy- 2 - ((5- methylthiazol -2- ylamino) methyl) naphthalene-1,4-dione
5℃에서 acetonitrile (15 mL) 중 교반된 용액 5-methyl-N-((1,4,5,8-tetramethoxynaphthalen-2-yl)methyl)thiazol-2-amine 730.2 mg (1.95 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 acetone 및 dimethyl ether로부터 재결정하였다.Yield: 59 % (396.3 mg).To a stirred solution of 5-methyl-N - ((1,4,5,8-tetramethoxynaphthalen-2-yl) methyl) thiazol-2-amine in 730.2 mg (1.95 mmol) of acetonitrile A solution of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in water was added. The reaction was stirred at ambient temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The result was recrystallized from acetone and dimethyl ether. Yield: 59% (396.3 mg).
1H NMR (300 MHz, DMSO) δ 9.72 (1H, t, J=6.0Hz), 7.57 (2H, s), 7.08 (1H, s), 6.58 (1H, s), 4.40 (2H, s), 3.86 (3H, s), 3.84 (3H, s), 2.23 (3H, s)
(1H, s), 4.40 (2H, s), 3.86 (2H, s), 7.58 (3H, s), 3.84 (3H, s), 2.23 (3H, s)
1-31 NQ08 -1. (1,4,5,8- Tetramethoxy - naphthalen -2- ylmethylene )-(4-p-tolyl-thiazol-2-yl)-amine 1-31 NQ08 -1. (1,4,5,8- Tetramethoxy - naphthalen -2- ylmethylene ) - (4-p- tolyl-thiazol-2-
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-4(p-tolyl)thiazole (1.38 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 3.0 g (Yield: 91%)을 수득하였다.20 mL of 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-4 (p (1.38 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol) and acetic acid (300 μl, pH 4-5) were added and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature and washed, and then the reaction mixture is continuously 5% HCL, saturated NaHCO 3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and hexane to give 3.0 g (Yield: 91%).
1H NMR (300 MHz, CDCl3) δ 9.45(1H, s), 7.85 (2H, d, J=9.6Hz), 7.65 (1H, s), 7.0 (2H, d, J=9.6Hz), 6.9 (2H, d, J=9.6Hz), 4.0 (12H, s), 2.2 (3H, s)
(1H, s), 7.0 (2H, d, J = 9.6 Hz), 6.9 (1H, s), 7.85 , d, J = 9.6 Hz), 4.0 (12H, s), 2.2 (3H, s)
1-32 NQ08 -2A. (1,4,5,8- Tetramethoxy - naphthalen -2- ylmethyl )-(4-p- tolyl -thiazol-2-yl)-amine 1-32 NQ08-2A . (1,4,5,8- Tetramethoxy - naphthalen -2- ylmethyl ) - (4-p- tolyl - thiazol- 2- yl) -amine
상온에서 tetrahydrofuran 30mL 중 교반된 용액인 NQ08-1 (2.20 g, 4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 1.76 g (Yield: 80%)을 수득하였다
The LiAlH 4 (195.7 mg, 4.90 mmol ) at room temperature to a stirred solution of 30mL of tetrahydrofuran NQ08-1 (2.20 g, 4.90 mmol) was added slowly over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to give 1.76 g (Yield: 80%)
1H NMR (300 MHz, CDCl3) δ 7.7 (2H, d, J=9.3Hz), 7.2 (2H, d, J=9.3Hz), 7.0 (1H, s), 2.8 (2H, s), 6.6 (1H, s), 4.7 (2H, d, J=6.8Hz), 4.0 (12H, s), 2.1 (3H, s)
(1H, s), 6.6 (2H, s), 6.6 (1H, d, J = 9.3Hz) , 4.7 (2H, d, J = 6.8Hz), 4.0 (12H, s), 2.1 (3H, s)
1-33 NQ08-4. (1,4,5,8-Tetramethoxy-naphthalen-2-ylmethyl)-(4-p-tolyl-thiazol-2-yl)-amine 1-33 NQ08-4. (1,4,5,8-Tetramethoxy-naphthalen-2-ylmethyl) - (4-p-tolyl-thiazol- 2- yl) -amine
상온에서 acetone (20 mL) 중 교반된 용액 NQ08-2A (882.5 mg, 1.95 mmol)에 H2SO4 160 μl, H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 dimethyl ether에 의해 화합물을 분리하였다. 529.5 g (Yield: 60%)160 μl of H 2 SO 4 , 4 mL of H 2 O and 203.2 mg (1.95 mmol) of CrO 3 were added to the stirred solution NQ08-2A (882.5 mg, 1.95 mmol) in acetone (20 mL) at room temperature. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The compounds were separated by acetone and dimethyl ether. 529.5 g (yield: 60%)
1H NMR (300 MHz, CDCl3) δ 7.7 (2H, d, J=9.3Hz), 7.2 (2H, d, J=9.3Hz), 7.0 (1H, s), 2.8 (2H, s), 6.6 (1H, s), 4.7 (2H, d, J=6.8Hz), 4.0 (6H, s), 2.1 (3H, s)
(1H, s), 6.6 (2H, s), 6.6 (1H, d, J = 9.3Hz) , 4.7 (2H, d, J = 6.8Hz), 4.0 (6H, s), 2.1 (3H, s)
1-34 NQ09 -1. N-[(1,4,5,8- Tetramethoxynaphthalen -2-yl)methylene]benzothiazol-2-amine 1-34 NQ09 -1. N - [(1,4,5,8- Tetramethoxynaphthalen -2- yl ) methylene] benzothiazol-2-amine
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Aminobenzothiazole (2.42 g, 7.25 mmol) , triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 5.4g (Yield: 91.3%)을 수득하였다.20 mL of benzene, 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol) and 2-Aminobenzothiazole (2.42 g, 7.25 mmol) were added to 100 mL of a round flask equipped with a Dean- 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μL, pH 4-5) was added and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature and washed, and then the reaction mixture is continuously 5% HCL, saturated NaHCO 3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and hexane to give 5.4 g (Yield: 91.3%).
1H NMR (300 MHz, CDCl) δ 9.48(1H, s), 8.02 (1H, d, J=8.1Hz), 7.85 (1H, d, J=7.9Hz), 7.68 (1H, s), 7.47 (1H, m), 7.38 (1H, m), 7.04 (1H, d, J=8.7Hz), 6.94 (1H, d, J=8.7Hz), 4.06 (3H, s), 4.01 (3H, s), 3.93 (3H, s), 3.94 (3H, s)
D, J = 7.9 Hz), 7.68 (1H, s), 7.47 (1H, s), 8.04 (1H, (1H, m), 7.38 (1H, m), 7.04 (1H, d, J = 8.7 Hz), 6.94 (1H, d, J = 8.7 Hz), 4.06 (3 H, s), 3.94 (3 H, s)
1-35 NQ09 -2A. 6- Methyl -N-[(1,4,5,8- tetramethoxynaphthalen -2- yl ) methyl ] benzothiazol-2-amine 1-35 NQ09-2A . 6- Methyl -N - [(1,4,5,8- tetramethoxynaphthalen -2- yl) methyl] benzothiazol-2-amine
상온에서 tetrahydrofuran 30mL 중 교반된 용액인 6-Methyl-N-[(1,4,5,8-tetramethoxynaphthalen-2-yl)methylene] benzothiazol-2-amine 4.14 g (4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 3.88g(Yield:93.4%)을 수득하였다.To a stirred solution of 6-Methyl-N - [(1,4,5,8-tetramethoxynaphthalen-2-yl) methylene] benzothiazol-2-amine in 30 mL tetrahydrofuran at room temperature was added LiAlH 4 (195.7 mg, , 4.90 mmol) was slowly added over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to obtain 3.88 g (Yield: 93.4%).
1H NMR (300 MHz, CDCl) δ 7.40 (1H, d, J=8.4Hz), 7.36 (1H, d, J=1.8Hz), 7.06 (1H, dd, J=8.4 and 1.8Hz), 6.95 (1H, s), 6.84 (2H, s), 6.26 (1H, s), 4.81 (2H, s), 3.96 (3H, s), 3.88 (3H, s), 3.85 (3H, s), 3.81 (3H, s), 2.37 (3H, s)
(1H, d, J = 8.4 and 1.8 Hz), 6.95 (1H, d, J = 3H, s), 3.84 (3H, s), 3.85 (3H, s), 3.84 s), 2.37 (3 H, s)
1-36 NQ09 -4. 6-[( benzothiazol -2- ylamino ) methyl ]-5,8-dimethoxynaphthalene-1,4-dione 1-36 NQ09 -4. 6 - [( benzothiazol -2- ylamino ) methyl ] -5,8- dimethoxynaphthalene-1,4-dione
상온에서 acetone (20 mL) 중 교반된 용액 N-[(1,4,5,8-Tetramethoxynaphthalen-2-yl)methyl]benzothiazol-2-amine 800 mg (1.95 mmol)에 H2SO4 160 μl(2.93 mmol), H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 dimethyl ether에 의해 화합물을 분리하였다. Yield: 62% (459.7 mg)To 800 mg (1.95 mmol) of N - [(1,4,5,8-Tetramethoxynaphthalen-2-yl) methyl] benzothiazol-2-amine in 20 mL of acetone at room temperature was added 160 μL of H 2 SO 4 2.93 mmol), H 2 O 4 mL, and CrO 3 203.2 mg (1.95 mmol). The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The compounds were separated by acetone and dimethyl ether. Yield: 62% (459.7 mg)
1H NMR (300 MHz, DMSO) δ 8.53 (1H, s), 7.68 (1H, d, J=8.0Hz), 7.66(1H, s), 7.39 (1H, d, J=7.6Hz), 7.23 (1H, t, J=7.2Hz), 7.04 (1H, t, J=6.6Hz), 6.82 (2H, s), 4.71 (2H, s), 3.81(3H, s), 3.78 (3H, s)
(1H, d, J = 7.6 Hz), 7.23 (1H, s), 7.68 (t, J = 7.2 Hz), 7.04 (1H, t, J = 6.6 Hz), 6.82 (2H, s), 4.71 (2H, s), 3.81
1-37 NQ09 -3. 2-[( benzothiazol -2- ylamino ) methyl ]-5,8-dimethoxynaphthalene-1,4-dione 1-37 NQ09 -3. 2 - [( benzothiazol -2- ylamino ) methyl ] -5,8- dimethoxynaphthalene-1,4-dione
5℃에서 acetonitrile (15 mL) 중 교반된 용액 N-[(1,4,5,8-Tetramethoxynaphthalen-2-yl)methyl]benzothiazol-2-amine 800 mg (1.95 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 ethyl ether에 의해 화합물을 분리하였다. Yield: 72 % (533 mg).To 800 mg (1.95 mmol) of N - [(1,4,5,8-Tetramethoxynaphthalen-2-yl) methyl] benzothiazol-2-amine in 5 mL of acetonitrile (15 mL) was added ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol). The reaction was stirred at ambient temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. acetone and ethyl ether. Yield: 72% (533 mg).
H NMR (300 MHz, DMSO) δ 8.37 (1H, t, J=5.7Hz), 7.69 (1H, d,J =7.3Hz), 7.55 (2H, s), 7.38 (1H, d, J=8.0Hz), 7.23 (1H, t, J=8.0Hz), 7.05 (1H, t, J=7.9Hz), 6.56 (1H, s), 4.45 (2H, d, J=5.7Hz), 3.86 (3H, s), 3.82 (3H,s)D, J = 7.3 Hz), 7.55 (2H, s), 7.38 (1H, d, J = 8.0 Hz, ), 7.23 (1H, t, J = 8.0 Hz), 7.05 (1H, t, J = 7.9 Hz), 6.56 (1H, s), 4.45 ), 3.82 (3 H, s)
1-38 NQ09 -6A. 5,8- Dihydroxy -6-[(6- methyl - benzothiazol -2- ylamino )-methyl]-[1,4]naphthoquinone 1-38 NQ09 -6A. 5,8- Dihydroxy -6 - [(6- methyl - benzothiazol -2- ylamino ) -methyl ] - [1,4] naphthoquinone
0~5℃에서 dry methylene chloride 40 mL 중 교반된 6-[(benzothiazol-2-ylamino)methyl]-5,8-dimethoxynaphthalene- 1,4-dione (473.3 mg, 1.2 mmol)에 AlCl3 (1.61 g, 11.9 mmol)를 천천히 첨가하였다. 혼합물을 2시간 동안 교반하였다. 교반된 차가운 용액 10% HCl (500 mL)에 반응 혼합물 및 ethyl ether (500 mL)을 천천히 첨가하였다. 혼합물을 ethyl ether로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 240 mg (Yield: 50.7%)을 수득하였다.To a stirred solution of 6 - [(benzothiazol-2-ylamino) methyl] -5,8-dimethoxynaphthalene-1,4-dione (473.3 mg, 1.2 mmol) in 40 mL of dry methylene chloride at 0-5 ° C was added AlCl 3 , 11.9 mmol) was slowly added. The mixture was stirred for 2 hours. To the stirred cold solution 10% HCl (500 mL) was slowly added the reaction mixture and ethyl ether (500 mL). The mixture was extracted with ethyl ether and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to give 240 mg (Yield: 50.7%).
1H NMR (300 MHz, CDCl3) δ 12.5 (2H, s), 7.45 (1H, d, J=9Hz), 7.4 (1H, s), 7.2 (2H, s), 7.15 (1H, s), 7.1 (1H, d, J=9.3Hz), 4.6 (2H, s), 2.5 (3H, s).
(1H, s), 7.1 (1H, s), 7.4 (1H, s), 7.4 1H, d, J = 9.3 Hz), 4.6 (2H, s), 2.5 (3H, s).
1-39 NQ09 -5. 5,8- Dihydroxy -2-[(6- methyl - benzothiazol -2- ylamino )-methyl]-[1,4]naphthoquinone 1-39 NQ09 -5. 5,8- Dihydroxy- 2 - [(6- methyl - benzothiazol -2- ylamino ) -methyl ] - [1,4] naphthoquinone
0~5℃에서 dry methylene chloride 40 mL 중 교반된 2-[(benzothiazol-2-ylamino)methyl]-5,8-dimethoxynaphthalene-1,4- dione (473.3 mg, 1.2 mmol)에 AlCl3 (1.61 g, 11.9 mmol)를 천천히 첨가하였다. 혼합물을 2시간 동안 교반하였다. 교반된 차가운 용액 10% HCl (500 mL)에 반응 혼합물 및 ethyl ether (500 mL)을 천천히 첨가하였다. 혼합물을 ethyl ether로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 240 mg (Yield: 50.7%)을 수득하였다.To a stirred solution of 2 - [(benzothiazol-2-ylamino) methyl] -5,8-dimethoxynaphthalene-1,4-dione (473.3 mg, 1.2 mmol) in 40 mL of dry methylene chloride at 0-5 ° C. was added AlCl 3 , 11.9 mmol) was slowly added. The mixture was stirred for 2 hours. To the stirred cold solution 10% HCl (500 mL) was slowly added the reaction mixture and ethyl ether (500 mL). The mixture was extracted with ethyl ether and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to give 240 mg (Yield: 50.7%).
1H NMR (300 MHz, CDCl3) δ 12.5 (2H, s), 7.45 (1H, d, J=9Hz), 7.4 (1H, s), 7.2 (2H, s), 7.15 (1H, s), 7.1 (1H, d, J=9.3Hz), 4.65 (2H, s), 2.45 (3H, s).
(1H, s), 7.1 (1H, s), 7.4 (1H, s), 7.4 1H, d, J = 9.3 Hz), 4.65 (2H, s), 2.45 (3H, s).
1-40 NQ10 -1. 4- methoxy -N-[(1,4,5,8- tetramethoxynaphthalen -2- yl ) methylene]benzothiazol-2-amine 1-40 NQ10 -1. 4- methoxy -N - [(1,4,5,8- tetramethoxynaphthalen -2- yl) methylene] benzothiazol-2-amine
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-amino-4-methoxy benzothiazole (2 g, 7.25 mmol) , triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 5.3 g (Yield: 85.6%)을 수득하였다.To 100 mL of a round flask equipped with a Dean-Stark trap and a condenser was added 20 mL of benzene, 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-amino- benzothiazole (2 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μL, pH 4-5) was added and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature and washed, and then the reaction mixture is continuously 5% HCL, saturated NaHCO 3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and hexane to give 5.3 g (Yield: 85.6%).
1H NMR (300 MHz, CDCl3) δ 9.44 (1H, s), 7.76 (1H, d, J=8.4Hz), 7.43 (1H, d), 7.36 (1H, s), 7.00 (1H, d, J=8.4Hz), 6.93 (1H, d, J=8.8Hz), 6.91 (1H, d, J=8.8Hz), 4.06 (3H, s), 4.04 (3H, s), 3.99 (3H, s), 3.92 (3H, s), 3.90 (3H, s), 2.17 (2H, s)
D, J = 8.4 Hz), 7.43 (1H, s), 7.00 (1H, s), 7.76 3H, s), 3.99 (3H, s), 3.92 (1H, d, J = 8.8Hz), 6.93 (3H, s), 3.90 (3H, s), 2.17 (2H, s)
1-41 NQ10 -2A. 4- methoxy -N-[(1,4,5,8- tetramethoxynaphthalen -2-yl)methyl]benzothiazol-2-amine 1-41 NQ10-2A . 4- methoxy -N - [(1,4,5,8- tetramethoxynaphthalen -2- yl) methyl] benzothiazol-2-amine
상온에서 tetrahydrofuran 30mL 중 교반된 용액인 4-methoxy-N-[(1,4,5,8-tetramethoxynaphthalen-2-yl)methylene] benzothiazol-2-amine 2.15 g (4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 3.88g(Yield:93.4%)을 수득하였다.
To a stirred solution of 4-methoxy-N - [(1,4,5,8-tetramethoxynaphthalen-2-yl) methylene] benzothiazol-2-amine in 30 mL of tetrahydrofuran at room temperature was added LiAlH 4 (195.7 mg, , 4.90 mmol) was slowly added over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to obtain 3.88 g (Yield: 93.4%).
*1H NMR (300 MHz, CDCl3) δ 8.90 (1H, s), 7.47 (1H, d, J=8.4Hz), 7.36 (1H, d), 7.27 (1H, s), 7.25 (1H, d, J=8.4Hz), 6.93 (1H, d, J=8.8Hz), 6.91 (1H, d, J=8.8Hz), 4.06 (3H, s), 4.04(3H, s), 3.99 (3H, s), 3.92 (3H, s), 3.90(3H, s), 3.30 (2H, d), 2.17(2H,s)
(1H, s), 7.27 (1H, d, J = 8.4Hz), 7.36 (1H, (3H, s), 3.99 (3H, s), 4.06 (3H, s), 6.93 (1H, d, J = 8.8Hz) 3.92 (3H, s), 3.90 (3H, s), 3.30 (2H, d), 2.17
1-42 NQ10 -4. 5,8- dimethoxy -6-[(4- methoxybenzothiazol -2-ylamino)methyl]naphthalen-1,4-dione 1-42 NQ10 -4. 5,8- dimethoxy -6- [(4- methoxybenzothiazol -2- ylamino) methyl] naphthalen-1,4-dione
상온에서 acetone (20 mL) 중 교반된 용액 4-methoxy-N-[(1,4,5,8-tetramethoxynaphthalen-2-yl)methyl] benzothiazol- 2-amine (858.4 mg, 1.95)에 H2SO4 160 μl (2.93 mmol), H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 ethyl ether에 의해 화합물을 분리하였다. Yield: 72.8% (582.6 mg).A solution of 4-methoxy-N stirred at room temperature acetone (20 mL) - a [(1,4,5,8-tetramethoxynaphthalen-2- yl) methyl] benzothiazol- 2-amine (858.4 mg, 1.95) H 2 SO 4 160 μl (2.93 mmol), H 2 O 4 mL, and CrO 3 203.2 mg (1.95 mmol) were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. acetone and ethyl ether. Yield: 72.8% (582.6 mg).
1H NMR (300 MHz, DMSO) δ 8.49 (1H, t, J=5.6Hz), 7.68 (1H, s), 7.26 (1H, d, J=1.02Hz), 7.00 (1H, t, J=8.0Hz), 6.84 (1H, d, J=8.0 and 1.2Hz), 6.81 (1H, d), 6.80 (1H, d) 4.68 (2H, d, J=5.6Hz), 3.84 (3H, s), 3.80 (3H, s), 3.79 (3H, s)
D, J = 1.02 Hz), 7.00 (1H, t, J = 8.0 Hz, 1H), 7.68 (1H, s), 7.26 ), 6.84 (1H, d, J = 8.0 and 1.2 Hz), 6.81 (1H, d), 6.80 3H, s), 3.79 (3H, s)
1-43 NQ10 -3. 5,8- dimethoxy -2-[(4- methoxy benzothiazol -2-ylamino)methyl]naphthalene-1,4-dione 1-43 NQ10 -3. 5,8- dimethoxy- 2 - [(4- methoxy benzothiazol -2- ylamino) methyl] naphthalene-1,4-dione
5℃에서 acetonitrile (15 mL) 중 교반된 용액 4-Methoxy-N-[(1,4,5,8-tetramethoxynaphthalen-2-yl)methyl]benzothiazol-2-amine 858.4 mg (1.95 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 ethyl ether에 의해 화합물을 분리하였다. Yield: 71.6 % (572.7 mg)To a stirred solution of 4-Methoxy-N - [(1,4,5,8-tetramethoxynaphthalen-2-yl) methyl] benzothiazol-2-amine 858.4 mg (1.95 mmol) in acetonitrile A solution of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in water was added. The reaction was stirred at ambient temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. acetone and ethyl ether. Yield: 71.6% (572.7 mg)
1H NMR (300 MHz, DMSO) δ 8.30 (1H, t, J=5.6Hz), 7.63 (1H, s), 7.62(1H, s), 7.27 (1H, d, J =8.0Hz), 7.01 (1H, t, J=8.0Hz), 6.83 (1H,d), 6.58 (1H, s), 4.45 (2H, d), 3.86 (3H, s), 3.82 (3H, s), 3.80(3H, s)
(1H, s), 7.27 (1H, d, J = 8.0Hz), 7.01 (1H, s), 7.63 (t, J = 8.0 Hz), 6.83 (1H, d), 6.58 (1H, s), 4.45 (2H, d), 3.86 (3H, s), 3.82
1-44 NQ10 -6A. 5,8- Dihydroxy -6-[(4- methoxy - benzothiazol -2- ylamino )-methyl]-[1,4]naphthoquinone 1-44 NQ10 -6A. 5,8- Dihydroxy- 6 - [(4- methoxy - benzothiazol -2- ylamino ) -methyl ] - [1,4] naphthoquinone
0~5℃에서 dry methylene chloride 40 mL 중 교반된 5,8-dimethoxy-6-[(4-methoxybenzothiazol-2-ylamino)methyl]naphthalen- 1,4-dione (492.6 mg, 1.2 mmol)에 AlCl3 (1.61 g, 11.9 mmol)를 천천히 첨가하였다. 혼합물을 2시간 동안 교반하였다. 교반된 차가운 용액 10% HCl (500 mL)에 반응 혼합물 및 ethyl ether (500 mL)을 천천히 첨가하였다. 혼합물을 ethyl ether로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 256 mg (Yield: 52.7%)을 수득하였다.4-methoxybenzothiazol-2-ylamino) methyl] naphthalen-1,4-dione (492.6 mg, 1.2 mmol) in 40 mL of dry methylene chloride at 0-5 ° C. was added AlCl 3 (1.61 g, 11.9 mmol) was slowly added. The mixture was stirred for 2 hours. To the stirred cold solution 10% HCl (500 mL) was slowly added the reaction mixture and ethyl ether (500 mL). The mixture was extracted with ethyl ether and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to give 256 mg (Yield: 52.7%).
1H NMR (300 MHz, DMSO) δ 8.5 (1H, s), 7.6 (1H, d, J=8.7Hz), 7.4 (1H, s), 7.25 (1H, d, J=9.3Hz), 7.1 (1H, s), 7.0 (1H, d, J=8.3Hz), 3.8 (2H, d, J=6.8Hz), 2.6 (2H, s), 2.1 (3H, s)
(1H, s), 7.25 (1H, d, J = 9.3 Hz), 7.1 (1H, s), 7.6 (2H, s), 7.0 (1H, d, J = 8.3 Hz), 3.8 (2H, d, J = 6.8Hz)
1-45 NQ10 -5. 5,8- Dihydroxy -2-[(4- methoxy - benzothiazol -2- ylamino )-methyl]-[1,4]naphthoquinone 1-45 NQ10 -5. 5,8- Dihydroxy- 2 - [(4- methoxy - benzothiazol -2- ylamino ) -methyl ] - [1,4] naphthoquinone
0~5℃에서 dry methylene chloride 40 mL 중 교반된 5,8-dimethoxy-2-[(4-methoxy benzothiazol-2-ylamino)methyl]naphthalene-1,4-dione (492.6 mg, 1.2 mmol)에 AlCl3 (1.61 g, 11.9 mmol)를 천천히 첨가하였다. 혼합물을 2시간 동안 교반하였다. 교반된 차가운 용액 10% HCl (500 mL)에 반응 혼합물 및 ethyl ether (500 mL)을 천천히 첨가하였다. 혼합물을 ethyl ether로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 256 mg (Yield: 52.7%)을 수득하였다.4-methoxybenzothiazol-2-ylamino) methyl] naphthalene-1,4-dione (492.6 mg, 1.2 mmol) in 40 mL of dry methylene chloride at 0-5 ° C was added AlCl 3 (1.61 g, 11.9 mmol) was slowly added. The mixture was stirred for 2 hours. To the stirred cold solution 10% HCl (500 mL) was slowly added the reaction mixture and ethyl ether (500 mL). The mixture was extracted with ethyl ether and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to give 256 mg (Yield: 52.7%).
1H NMR (300 MHz, DMSO) δ 8.5 (1H, s), 7.6 (1H, d, J=8.7Hz), 7.4 (1H, s), 7.25 (1H, d, J=9.3Hz), 7.1 (1H, s), 7.0 (1H, d, J=8.3Hz), 3.8 (2H, d, J=6.0Hz), 2.6 (2H, s), 2.1 (3H, s)
(1H, s), 7.25 (1H, d, J = 9.3 Hz), 7.1 (1H, s), 7.6 (2H, s), 7.0 (1H, d, J = 8.3 Hz), 3.8
1-46 NQ11 -1. N-[(1,4,5,8- tetramethoxynaphthalen -2-yl)methylene]naphthalene-2-sulfonamide 1-46 NQ11 -1. N - [(1,4,5,8- tetramethoxynaphthalen -2- yl ) methylene] naphthalene-2-sulfonamide
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), naphthalene -2-sulfonamide 2 g (9.65 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 4.14 g (Yield: 73.6%)을 수득하였다.20 mL of 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol) and 2 g of naphthalene-2-sulfonamide were added to 100 mL of a round flask equipped with a Dean-Stark trap and a condenser. (9.65 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μL, pH 4-5) was added and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature and washed, and then the reaction mixture is continuously 5% HCL, saturated NaHCO 3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and hexane to give 4.14 g (Yield: 73.6%).
1H NMR (300 MHz, CDCl3 ) δ 8.90 (1H, s), 7.47 (1H, s), 7.27 (1H, d), 7.25 (1H, d), 6.89 (1H, d, J=8.4Hz), 4.65 (1H, d, J=8.8Hz), 3.95 (3H, s, J=8.8Hz), 3.94 (3H, s), 3.82 (3H, s), 3.22 (2H, t), 2.19 (2H,d)
(1H, s), 7.27 (1H, d), 7.25 (1H, d), 6.89 (1H, d, J = 8.4Hz), 4.65 (1H, d, J = 8.8Hz), 3.95 (3H, s, J = 8.8Hz), 3.94 (3H, s), 3.82
1-47 NQ 11-2A. N-[(1,4,5,8- tetramethoxynaphthalen -2-yl)methyl]naphthalene-2-sulfonamide 1-47 NQ 11-2A. N - [(1,4,5,8- tetramethoxynaphthalen -2- yl ) methyl] naphthalene-2-sulfonamide
상온에서 tetrahydrofuran 30mL 중 교반된 용액인 N-[(1,4,5,8-tetramethoxynaphthalen-2-yl)methylene]naphthalene-2-sulfonamide 2.28 g (4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 3.92g(Yield:93.4%)을 수득하였다.LiAlH 4 (195.7 mg, 4.90 mmol) was added to 2.28 g (4.90 mmol) of N - [(1,4,5,8-tetramethoxynaphthalen-2-yl) methylene] naphthalene- 2 -sulfonamide in 30 mL of tetrahydrofuran at room temperature. Was slowly added over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to give 3.92 g (Yield: 93.4%).
1H NMR (300 MHz, CDCl3 ) δ 7.30 (1H, d, J=8.4Hz), 7.20 (1H, d, J=1.8Hz), 7.19 (1H, dd, J=8.4 and 1.8Hz), 7.06 (1H, s), 7.01 (1H, s), 6.87 (2H, d), 4.82 (2H, s), 3.96 (3H, s), 3.88 (3H, s), 3.85 (3H, s), 3.81 (3H, s), 2.17 (1H, s)
(1H, d, J = 8.4 and 1.8 Hz), 7.06 (1H, d, J = , 3.81 (3H, s), 3.88 (3H, s), 3.85 (3H, s), 3.81 s), 2.17 (1 H, s)
1-48 NQ 11-4. N-[(1,4- dimethoxy -5,8- dioxo -5,8- dihydronaphthalen -2-yl)methyl]naphthalene-2-sulfonamide 1-48 NQ 11-4. N - [(1,4- dimethoxy -5,8- dioxo -5,8- dihydronaphthalen -2- yl) methyl] naphthalene-2-sulfonamide
상온에서 acetone (20 mL) 중 교반된 용액 N-[(1,4,5,8-Tetramethoxynaphthalen-2-yl)methyl]naphthalene-2-sulfonamide 941 mg (1.95 mmol)에 을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 ethyl ether에 의해 화합물을 분리하였다. Yield: 72.8% (625.8 mg)To a stirred solution of N - [(1,4,5,8-Tetramethoxynaphthalen-2-yl) methyl] naphthalene-2-sulfonamide (941 mg, 1.95 mmol) in acetone (20 mL) was added at room temperature. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. acetone and ethyl ether. Yield: 72.8% (625.8 mg)
1H NMR (300 MHz, DMSO) δ 8.43 (1H, t, J=5.6Hz), 7.58 (1H, s), 7.45 (1H, d, J=1.2Hz), 7.25 (1H, d, J=8.0Hz), 7.00 (1H, dd, J=8.0 and 1.2Hz), 6.79 (2H, s), 4.67 (2H, d, J=5.6Hz), 3.79 (3H, s), 3.76 (3H, s), 2.76 (3H,s)
(1H, d, J = 8.0 Hz), 7.45 (1H, d, J = 3H, s), 3.76 (3H, s), 2.76 (3H, s), 7.00 (1H, d, J = (3H, s)
1-49 NQ11 -3. N-[(5,8- dimethoxy -1,4- dioxo -1,4- dihydro naphthalen -2-yl)methyl]naphthalene-2-sulfonamide 1-49 NQ11 -3. N - [(5,8- dimethoxy- 1,4- dioxo- 1,4- dihydro naphthalen -2- yl) methyl] naphthalene- 2-sulfonamide
5℃에서 acetonitrile (15 mL) 중 교반된 용액 N-[(1,4,5,8-Tetramethoxynaphthalen-2-yl)methyl]naphthalene-2-sulfonamide 941 mg (1.95 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 ethyl ether에 의해 화합물을 분리하였다. Yield: 71.6 % (612.5 mg)To a stirred solution of N - [(1,4,5,8-Tetramethoxynaphthalen-2-yl) methyl] naphthalene-2-sulfonamide (941 mg, 1.95 mmol) in acetonitrile (15 mL) at 5 ° C. was added ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol). The reaction was stirred at ambient temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. acetone and ethyl ether. Yield: 71.6% (612.5 mg)
1H NMR (300 MHz, DMSO) δ 8.28 (1H, t, J=5.6Hz), 7.56 (2H, s), 7.47 (1H, s), 7.25 (1H, d, J=8.0Hz), 7.01 (1H, d, J=8.0Hz), 6.54 (1H, s), 4.44 (2H, s), 3.85 (3H, s), 3.81 (3H, s), 2.89 (3H, s)
(1H, s), 7.25 (1H, d, J = 8.0Hz), 7.01 (1H, (d, J = 8.0 Hz), 6.54 (1H, s), 4.44 (2H, s), 3.85 (3H, s), 3.81
1-50 NQ12 -1. N-[(1,4,5,8- tetramethoxynaphthalen -2- yl ) methylene ]-2,3-dihydro-1H-inden-2-amine 1-50 NQ12 -1. N - [(1,4,5,8- tetramethoxynaphthalen -2- yl ) methylene ] -2,3- dihydro-1H-inden-
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-aminoindan 1.93 g (7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 5.24 g (Yield: 85.6%)을 수득하였다.To 100 mL of a round flask equipped with a Dean-Stark trap and a condenser were added 20 mL of benzene, 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-aminoindan 1.93 g mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5) was added and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature and washed, and then the reaction mixture is continuously 5% HCL, saturated NaHCO 3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and hexane to give 5.24 g (Yield: 85.6%).
1H NMR (300 MHz, CDCl3 ) δ 9.44 (1H, s), 7.89 (1H, d, J=8.4Hz), 7.67 (1H, s), 7.63 (1H, s), 7.29 (1H, d, J=8.4Hz), 7.03 (1H, d, J=8.8Hz), 6.93 (1H, d, J=8.8Hz), 4.04 (3H, s), 4.00 (3H, s), 3.91 (3H, s), 2.50 (3H,s)
D, J = 8.4 Hz), 7.67 (1H, s), 7.63 (1H, s), 7.29 3H, s), 3.91 (3H, s), 2.50 (1H, d, J = 8.8Hz), 7.03 (3H, s)
1-51 NQ12 -2A. N-[(1,4,5,8- tetramethoxynaphthalen -2- yl ) methyl ]-2,3-dihydro-1H-inden-2-amine 1-51 NQ12-2A . N - [(1,4,5,8- tetramethoxynaphthalen -2- yl ) methyl ] -2,3- dihydro-1H-inden-
상온에서 tetrahydrofuran 30mL 중 교반된 용액인 N-[(1,4,5,8-tetramethoxynaphthalen-2-yl)methylene]-2,3-dihydro-1H-inden- 2-amine 4.6 g (4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 3.5g (Yield: 87.3%)을 수득하였다.To a stirred solution of N - [(1,4,5,8-tetramethoxynaphthalen-2-yl) methylene] -2,3-dihydro-1H-inden-2-amine in 30 mL of tetrahydrofuran at room temperature was added 4.6 g the LiAlH 4 (195.7 mg, 4.90 mmol ) was added slowly over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to give 3.5 g (Yield: 87.3%).
1H NMR (300 MHz, CDCl3 ) δ 7.55 (1H, d, J=7.8Hz), 7.46 (1H, d, J=8.2Hz), 7.23 (1H, t, J=8.0Hz), 7.09 (1H, t, J=7.4Hz), 6.96 (1H, s), 6.83 (2H, s), 4.83 (2H, s), 3.96 (3H, s), 3.88 (3H, s), 3.82 (6H,s)
(1H, t, J = 8.0 Hz), 7.09 (1H, t, J = 7.8 Hz) , 3.96 (3H, s), 3.88 (3H, s), 3.82 (6H, s)
1-52 NQ12 -4. 6-[(2,3- dihydro -1H- inden - ylamino ) methyl ]-5,8-dimethoxynaphthalene-1,4-dione 1-52 NQ12 -4. 6 - [(2,3- dihydro- 1H- inden - ylamino ) methyl ] -5,8- dimethoxynaphthalene- 1,4-dione
상온에서 acetone (20 mL) 중 교반된 용액 N-[(1,4,5,8-tetramethoxynaphthalen-2-yl)methyl]-2,3-dihydro- 1H-inden-2-amine 770 mg (1.95 mmol)에 H2SO4 160 μl (2.93 mmol), H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 ethyl ether에 의해 화합물을 분리하였다. Yield: 62% (459.7 mg).A solution of 770 mg (1.95 mmol) of N - [(1,4,5,8-tetramethoxynaphthalen-2-yl) methyl] -2,3- dihydro-1H- inden-2-amine in acetone (20 mL) ) Was added H 2 SO 4 160 μl (2.93 mmol), 4 mL of H 2 O and 203.2 mg (1.95 mmol) of CrO 3 were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. acetone and ethyl ether. Yield: 62% (459.7 mg).
1H NMR (300 MHz, DMSO) δ 8.53 (1H, s), 7.68 (1H, d, J=8.0Hz), 7.66 (1H, s), 7.39 (1H, d, J=7.6Hz), 7.23 (1H, t, J=7.2Hz), 7.04 (1H, t, J=6.6Hz), 6.82 (2H, s), 4.71 (2H, s), 3.81 (3H, s), 3.78 (3H, s)
(1H, d, J = 7.6 Hz), 7.23 (1H, s), 7.68 (t, J = 7.2 Hz), 7.04 (1H, t, J = 6.6 Hz), 6.82 (2H, s), 4.71 (2H, s), 3.81
1-53 NQ12 -3. 2-[(2,3- Dihydro -1H- inden - ylamino ) methyl ]-5,8- dimethoxy naphthalene-1,4-dion 1-53 NQ12 -3. 2 - [(2,3- Dihydro- 1H- inden - ylamino ) methyl ] -5,8- dimethoxy naphthalene-1,4-dion
5℃에서 acetonitrile (15 mL) 중 교반된 용액 N-[(1,4,5,8-tetramethoxynaphthalen-2-yl)methyl]-2,3-dihydro- 1H-inden-2-amine 770 mg (1.95 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 ethyl ether에 의해 화합물을 분리하였다. Yield: 72 % (533 mg).770 mg (1.95 mmol) of N - [(1,4,5,8-tetramethoxynaphthalen-2-yl) methyl] -2,3-dihydro-1H- inden-2-amine in acetonitrile mmol) was added a solution of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in 3.5 mL water. The reaction was stirred at ambient temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. acetone and ethyl ether. Yield: 72% (533 mg).
1H NMR (300 MHz, DMSO) δ 8.37 (1H, t, J=5.7Hz), 7.69 (1H, d, J=7.3Hz), 7.55 (2H, s), 7.38 (1H, d, J=8.0Hz), 7.23 (1H, t, J=8.0Hz), 7.05 (1H, t, J=7.9Hz), 6.56 (1H, s), 4.45 (2H, d, J=5.7Hz), 3.86 (3H, s), 3.82(3H, s)
(2H, s), 7.38 (1H, d, J = 8.0Hz, 1H), 7.59 (1H, d, J = ), 7.23 (1H, t, J = 8.0 Hz), 7.05 (1H, t, J = 7.9 Hz), 6.56 (1H, s), 4.45 ), 3.82 (3 H, s)
1-54 NQ13 -1. 5-( methylthio )-N-((1,4,5,8- tetramethoxynaphthalen -2-yl)methylene)-1,3,4-thiadiazol-2-amine 1-54 NQ13 -1. 5- ( methylthio ) -N - ((1,4,5,8- tetramethoxynaphthalen -2- yl) methylene) -1,3,4-thiadiazol-2-amine
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-5-(methylthio)-1,3,4- thiadiazole 1.06 g (7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 2.76 g (Yield: 93.9%)을 수득하였다.20 mL of 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-amino-5- ( 1.06 g (7.25 mmol), triethylamine (1.03 mL, 7.25 mmol) and acetic acid (300 μL, pH 4-5) were added and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature and washed, and then the reaction mixture is continuously 5% HCL, saturated NaHCO 3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and hexane to give 2.76 g (Yield: 93.9%).
1H NMR(300 MHz, DMSO) δ 9.07 (1H, s), 7.36 (1H, s), 7.14 (2H, d, J=8.4Hz), 4.02 (3H, s), 4.00 (3H, s), 3.83 (3H, s), 3.81 (3H, s), 2.78(3H, s)
(1H, s), 7.14 (2H, d, J = 8.4 Hz), 4.02 (3H, s), 4.00 (3H, s), 3.83 (3H, s), 3.81 (3H, s), 2.78 (3H, s)
1-55 NQ13 -2A. 5-( methylthio )-N-((1,4,5,8- tetramethoxynaphthalen -2-yl)methyl-1,3,4-thiadiazol-2-amine 1-55 NQ13-2A . 5- ( methylthio ) -N - ((1,4,5,8- tetramethoxynaphthalen -2- yl) methyl-1,3,4-thiadiazol-2-amine
상온에서 tetrahydrofuran 30mL 중 교반된 용액인 5-(methylthio)-N-((1,4,5,8-tetramethoxynaphthalen-2-yl)methylene -1,3,4-thiadiazol-2-amine1.99 g (4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 1.76g (Yield: 88.1%)을 수득하였다.To a stirred solution of 5- (methylthio) -N - ((1,4,5,8-tetramethoxynaphthalen-2-yl) methylene-1,3,4-thiadiazol-2-amine in 30 mL of tetrahydrofuran at room temperature the LiAlH 4 (195.7 mg, 4.90 mmol ) in 4.90 mmol) was added slowly over 10 minutes. the mixture was stirred at room temperature for 30 minutes. the reaction mixture was extracted with methylene chloride and washed with water. MgSO the organic layer 4 , And concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to give 1.76 g (Yield: 88.1%).
1H NMR (300 MHz, DMSO) δ 8.18 (1H, t, J=6.0Hz), 6.95 (1H, s), 6.91 (2H, d, J=11.4Hz), 4.59 (2H, d, J=6.0Hz), 3.83 (3H, s), 3.76 (3H, s), 3.75 (3H, s), 3.64 (3H, s), 2.64 (3H, s)
J = 6.0 Hz), 6.95 (1H, s), 6.91 (2H, d, J = 11.4 Hz), 4.59 (2H, ), 3.83 (3H, s), 3.76 (3H, s), 3.75
1-56 NQ13 -4. 5,8- dimethoxy -6-((5-( methylthio )-1,3,4- thiadiazol -2ylamino)methyl)naphthalene-1,4-dione 1-56 NQ13 -4. 5,8- dimethoxy- 6 - ((5- ( methylthio ) -1,3,4- thiadiazol - 2ylamino) methyl) naphthalene- 1,4-dione
상온에서 acetone (20 mL) 중 교반된 용액 5-(methylthio)-N-((1,4,5,8-tetramethoxynaphthalen-2-yl)methyl-1,3,4- thiadiazol-2-amine 793.6 mg (1.95 mmol)에 H2SO4 160 μl (2.93 mmol), H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 ethyl ether에 의해 화합물을 분리하였다 Yield: 69.6% (512.3 mg).To a stirred solution of 5- (methylthio) -N - ((1,4,5,8-tetramethoxynaphthalen-2-yl) methyl-1,3,4-thiadiazol-2-amine in acetone (20 mL) (1.95 mmol) was added H 2 SO 4 160 μl (2.93 mmol), 4 mL of H 2 O and 203.2 mg (1.95 mmol) of CrO 3 were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. acetone and ethyl ether. Yield: 69.6% (512.3 mg).
1H NMR (300 MHz, DMSO) δ 8.27.(1H, t, J=6.0Hz), 7.52 (1H, s), 6.81 (2H, s), 4.59 (2H, d, J=5.4Hz), 3.82 (3H, s), 3.74 (3H, s), 2.57(3H, s)
(2H, s), 4.59 (2H, d, J = 5.4Hz), 3.82 (1H, d, J = 6.0Hz) 3H, s), 3.74 (3H, s), 2.57 (3H, s)
1-57 NQ13 -3. 5,8- dimethoxy -2-((5-( methylthio )-1,3,4- thiadiazol -2-ylamino)methyl)naphthalene-1,4-dione 1-57 NQ13 -3. 5,8- dimethoxy- 2 - ((5- ( methylthio ) -1,3,4- thiadiazol -2- ylamino) methyl) naphthalene- 1,4-dione
5℃에서 acetonitrile (15 mL) 중 교반된 용액 5-(methylthio)-N-((1,4,5,8-tetramethoxynaphthalen-2-yl)methyl-1,3,4- thiadiazol-2-amine 793.6 mg (1.95 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 ethyl ether에 의해 화합물을 분리하였다. Yield: 60 % (488 mg)2-yl) methyl-1,3,4-thiadiazol-2-amine < / RTI > 793.6 < RTI ID = 0.0 > mg (1.95 mmol) of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in 3.5 mL of water was added to the reaction mixture and the reaction mixture was stirred at room temperature for 1 hour The reaction mixture was extracted with methylene chloride and washed with water The organic layer was dried over MgSO 4 , concentrated under reduced pressure, and the compound was isolated by acetone and ethyl ether yield: 60% (488 mg)
1H NMR (300 MHz, DMSO) δ 8.09 (1H, t, J=6.0Hz), 7.54 (2H,s), 6.53 (1H, s), 4.32 (2H, d, J=6.0Hz), 3.84 (3H, s), 3.82 (3H, s), 2.50 (3H, s)
(1H, s), 4.32 (2H, d, J = 6.0 Hz), 3.84 (3H , s), 3.82 (3H, s), 2.50 (3H, s)
1-58 NQ14 -1. 4- methyl -N-((1,4,5,8- tetramethoxynaphthalen -2-yl)methylene)thiazol-2-amine 1-58 NQ14 -1. 4- methyl -N - ((1,4,5,8- tetramethoxynaphthalen -2- yl) methylene) thiazol-2-amine
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-4-methylthiazole (827.7 mg, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 2.47 g (Yield: 91.2%)을 수득하였다. 20 mL of 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol) and 2-amino-4-methylthiazole were added to 100 mL of a round flask equipped with a Dean-Stark trap and a condenser. (827.7 mg, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μL, pH 4-5) and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature and washed, and then the reaction mixture is continuously 5% HCL, saturated NaHCO 3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and hexane to give 2.47 g (Yield: 91.2%).
1H NMR (300 MHz, CDCl3) δ 6.9 (1H, s), 6.8 (2H, d, J=9.7Hz), 6.1 (1H, s), 4.0 (12H, s), 2.25 (3H, s)
(1H, s), 2.25 (3H, s), 6.8 (2H, d, J =
1-59 NQ14 -2A. 4- methyl -N-((1,4,5,8- tetramethoxynaphthalen -2-yl)methyl)thiazol-2-amine 1-59 NQ14 -2A . 4- methyl -N - ((1,4,5,8- tetramethoxynaphthalen -2- yl) methyl) thiazol-2-amine
상온에서 tetrahydrofuran 30mL 중 교반된 용액인 4-methyl-N-((1,4,5,8-tetramethoxynaphthalen-2yl)methylene)thiazol-2-amine (1.82 g, 4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 1.69 g (Yield: 91.7%)을 수득하였다.LiAlH 4 (195.7 mg, 4.90 mmol) was added to a stirred solution of 4-methyl-N - ((1,4,5,8-tetramethoxynaphthalen-2yl) methylene) thiazol- 4.90 mmol) was slowly added over 10 min. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to give 1.69 g (Yield: 91.7%).
1H NMR (300 MHz, CDCl3) δ 6.9 (1H, s), 6.8 (2H, d, J=9.7Hz), 6.1 (1H, s), 4.65 (2H, d, J=7.3Hz), 4.0 (12H, s), 2.25 (3H, s)
(1H, s), 4.65 (2H, d, J = 7.3Hz), 4.0 (1H, s), 6.8 , < / RTI > s), 2.25 (3H, s)
1-60 NQ14 -4. 5,8- dimethoxy -6-((4- methylthiazol -2-ylamino)methyl)naphthalene-1,4-dione 1-60 NQ14 -4. 5,8- dimethoxy -6- ((4- methylthiazol -2- ylamino) methyl) naphthalene-1,4-dione
상온에서 acetone (20 mL) 중 교반된 용액 4-methyl-N-((1,4,5,8-tetramethoxynaphthalen-2-yl)methyl)thiazol-2-amine (730.2 mg, 1.95 mmol)에 H2SO4 160 μl, H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 dimethyl ether에 의해 화합물을 분리하였다. (Yield: 51.7%) 377.4 mgA solution of 4-methyl-N was stirred at room temperature acetone (20 mL) - a ((1,4,5,8-tetramethoxynaphthalen-2- yl) methyl) thiazol-2-amine (730.2 mg, 1.95 mmol) H 2 160 μl of SO 4 , 4 mL of H 2 O and 203.2 mg (1.95 mmol) of CrO 3 were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The compounds were separated by acetone and dimethyl ether. (Yield: 51.7%) 377.4 mg
1H NMR (300 MHz, CDCl3) δ 6.9 (1H, s), 6.8 (2H, d, J=9.7Hz), 6.1 (1H, s), 4.65 (2H, d, J=7.3Hz), 4.0 (6H, s), 2.25 (3H, s)
(1H, s), 4.65 (2H, d, J = 7.3 Hz), 4.0 (1H, s), 6.8 , < / RTI > s), 2.25 (3H, s)
1-61 NQ14 -3. 5,8- dimethoxy -2-((4- methylthiazol -2-ylamino)methyl)naphthalene-1,4-dione 1-61 NQ14 -3. 5,8- dimethoxy- 2 - ((4- methylthiazol -2- ylamino) methyl) naphthalene-1,4-dione
5℃에서 acetonitrile (15 mL) 중 교반된 용액 4-methyl-N-((1,4,5,8-tetramethoxynaphthalen-2-yl)methyl)thiazol-2-amine (730.2 mg, 1.95 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 dimethyl ether에 의해 화합물을 분리하였다. (Yield: 40.7%) 285.7 mgTo a stirred solution of 4-methyl-N - ((1,4,5,8-tetramethoxynaphthalen-2-yl) methyl) thiazol-2-amine (730.2 mg, 1.95 mmol) in acetonitrile mL solution of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol). The reaction was stirred at ambient temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The compounds were separated by acetone and dimethyl ether. (Yield: 40.7%) 285.7 mg
1H NMR (300 MHz, CDCl3) δ 6.9 (1H, s), 6.8 (2H, d, J=9.7Hz), 6.1(1H, s), 4.65 (2H, d, J=7.3Hz), 4.0 (6H, s), 2.25(3H, s)
(1H, s), 4.65 (2H, d, J = 7.3 Hz), 4.0 (1H, s), 6.8 , < / RTI > s), 2.25 (3H, s)
1-62 NQ15 -4. 6-[(5- Chloro - benzooxazol -2- ylamino )- methyl ]-5,8- dimethoxy -[1,4]naphthoquinone 1-62 NQ15 -4. 6 - [(5- Chloro - benzooxazol -2- ylamino) - methyl] -5,8- dimethoxy - [1,4] naphthoquinone
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-5-chlorobenzoxarole (1.22 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 2.78 g (Yield: 89.9%)을 수득하여 (5-chloro-benzooxazol-2-yl)-(1,4,5,8-tetramethoxy-naphthalen-2-ylmethylene)-amine을 합성하였다.20 mL of 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), and 2-Amino-5-chlorobenzoxarole are added to 100 mL of a round flask equipped with a Dean-Stark trap and a condenser. (1.22 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5) was added and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature, the reaction mixture was washed successively with 5% HCl, saturated NaHCO3, 5% acetic acid and water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The resulting product was recrystallized from ethyl acetate and hexane to obtain 2.78 g (yield: 89.9%) of 5-chloro-benzooxazol-2-yl) - (1,4,5,8-tetramethoxy-naphthalen- -amine.
1H NMR (300 MHz, CDCl3) δ 9.9 (1H, s), 7.7 (1H, d, J=9.6Hz), 7.65 (1H, s), 7.45 (1H, s), 7.3 (1H, d, J=9.6Hz), 7.1 (1H, d, J=10Hz), 6.9 (1H, d, J=10Hz), 4.0 (12H, s)D, J = 9.6 Hz), 7.65 (1H, s), 7.45 (1H, s), 7.3 (1H, d, J = (1H, d, J = 10 Hz), 7.1 (1H, d, J =
다시 상온에서 tetrahydrofuran 30mL 중 교반된 용액인 (5-chloro-benzooxazol-2-yl)-(1,4,5,8-tetramethoxy-naphthalen-2-ylmethylene)-amine (2.09 g, 4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)을 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 1.75g (Yield: 83.7%))의 (5-chloro-benzooxazol-2-yl)-(1,4,5,8-tetramethoxy-naphthalen-2-ylmethyl)-amine을 수득하였다.To a stirred solution of 5-chloro-benzooxazol-2-yl- (1,4,5,8-tetramethoxy-naphthalen-2-ylmethylene) -amine (2.09 g, 4.90 mmol) in 30 mL of tetrahydrofuran at room temperature was added LiAlH4 (195.7 mg, 4.90 mmol) was slowly added over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The resulting product was recrystallized from ethyl ether to obtain 1.75 g (Yield: 83.7%) of 5-chloro-benzooxazol-2-yl) - (1,4,5,8-tetramethoxy-naphthalen-2-ylmethyl) Respectively.
1H NMR (300 MHz, CDCl3) δ 7.3 (1H, d, J=9.6Hz), 7.15 (1H, s), 7.0 (1H, s), 6.9 (1H, d, J=9.6Hz), 7.1 (1H, d, J=10Hz), 6.9 (2H, d, J=10Hz), 5.7 (1H, t, J=6.8Hz), 4.8 (2H, d, J=6.8Hz), 4.0 (12H, s)D, J = 9.6 Hz), 7.1 (1H, s), 7.0 (1H, s), 6.9 (d, J = 10 Hz), 6.9 (2H, d, J = 10 Hz), 5.7 (1H, t, J = 6.8 Hz), 4.8
이후 상온에서 acetone (20 mL) 중 교반된 용액 (5-chloro-benzooxazol-2-yl)-(1,4,5,8-tetramethoxy-naphthalen-2-ylmethyl)-amine (836.17 mg, 1.95 mmol)에 H2SO4 160 μl, H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔 상(ethyl acetate :n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 87.6% (732.5 mg)Then, 5-chloro-benzooxazol-2-yl- (1,4,5,8-tetramethoxy-naphthalen-2-ylmethyl) -amine (836.17 mg, 1.95 mmol) in acetone (20 mL) , 160 [mu] l of H2SO4, 4 ml of H2O and 203.2 mg (1.95 mmol) of CrO3 were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 87.6% (732.5 mg)
1H NMR (300 MHz, CDCl3) δ 7.3 (1H, d, J=9.6Hz), 7.15 (1H, s), 7.0 (1H, s), 6.9 (1H, d, J=9.6Hz), 7.1 (1H, d, J=10Hz), 6.9 (2H, d, J=10Hz), 5.7 (1H, t, J=6.8Hz), 4.8 (2H, d, J=6.8Hz), 4.0 (6H, s)
D, J = 9.6 Hz), 7.1 (1H, s), 7.0 (1H, s), 6.9 d, J = 10 Hz), 6.9 (2H, d, J = 10 Hz), 5.7 (1H, t, J = 6.8 Hz), 4.8
1-63 NQ15 -3. 2-[(5- Chloro - benzooxazol -2- ylamino )- methyl ]-5,8- dimethoxy -[1,4]naphthoquinone 1-63 NQ15 -3. 2 - [(5- Chloro - benzooxazol -2- ylamino) - methyl] -5,8- dimethoxy - [1,4] naphthoquinone
5℃에서 acetonitrile (15 mL) 중 교반된 용액 (5-chloro-benzooxazol-2-yl)-(1,4,5,8-tetramethoxy-naphthalen-2-ylmethyl)-amine (836.17 mg, 2 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔 상(ethyl acetate :n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 52.9% (442.24 mg) 5-chloro-benzooxazol-2-yl) - (1,4,5,8-tetramethoxy-naphthalen-2- ylmethyl) -amine (836.17 mg, 2 mmol) in acetonitrile (15 mL) Was added a solution of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in 3.5 mL of water. The reaction was stirred at ambient temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 52.9% (442.24 mg)
1H NMR (300 MHz, CDCl3) δ 7.3 (1H, d, J=9.6Hz), 7.15 (1H, s), 7.0 (1H, s), 6.9 (1H, d, J=9.6Hz), 7.1 (1H, d, J=10Hz), 6.9 (2H, d, J=10Hz), 5.7 (1H, t, J=6.8Hz), 4.8 (2H, d, J=6.8Hz), 4.0 (6H, s)
D, J = 9.6 Hz), 7.1 (1H, s), 7.0 (1H, s), 6.9 d, J = 10 Hz), 6.9 (2H, d, J = 10 Hz), 5.7 (1H, t, J = 6.8 Hz), 4.8
1-64 NQ16 -4. 6-{[6- Ethoxy -1,3- benzothiazol -2- yl ) amino ] methyl }-5,8-dimethoxy-1,4-dihydro-1,4-naphthalenedione 1-64 NQ16 -4. 6 - {[ Ethoxy -1,3- benzothiazol -2- yl ) amino ] methyl } -5,8- dimethoxy- 1,4-dihydro-1,4-naphthalenedione
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-6-ethoxybenzothiazole (1.41 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 2.86 g (Yield: 86.8%)의 N-(6-Ethoxy-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl)methylidene]amine을 수득하였다.20 mL of benzene, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol) and 2-Amino-6-ethoxybenzothiazole were added to 100 mL of a round flask equipped with a Dean- (1.41 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5) and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature, the reaction mixture was washed successively with 5% HCl, saturated NaHCO3, 5% acetic acid and water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The resulting product was recrystallized from ethyl acetate and hexane to give 2.86 g (Yield: 86.8%) of N- (6-Ethoxy-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy -2-naphthyl) methylidene] amine.
M.p: 162 - 169℃M.p .: 162-169 ° C
1H NMR (200 MHz, CDCl3) δ 9.39 (1H, s), 7.88 (1H, d, J=8.8Hz), 7.66 (1H, s), 7.29 (1H, d, J=2.4Hz), 7.07 (1H, dd, J=8.8Hz), 4.11 (2H, q, J=7.0Hz), 4.04 (3H, s), 4.00 (3H, s), 3.92 (3H, s), 3.91 (3H, s), 1.47 (3H, t, J=7.0Hz)(1H, s), 7.29 (1H, d, J = 2.4Hz), 7.07 (1H, s), 7.88 s), 3.91 (3H, s), 3.91 (3H, s), 1.47 (3H, s) (3H, t, J = 7.0 Hz)
이후 상온에서 tetrahydrofuran 30mL 중 교반된 용액인 N-(6-Ethoxy-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine (2.22 g, 4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 1.95 g (Yield: 83.7%)의 N-(6-Ethoxy-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl)methyl]amine을 수득하였다. Then, a solution of N- (6-Ethoxy-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine 2.22 g, 4.90 mmol) was slowly added LiAlH4 (195.7 mg, 4.90 mmol) over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The resulting product was recrystallized from ethyl ether to obtain 1.95 g (yield: 83.7%) of N- (6-Ethoxy-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy- naphthyl) methyl] amine.
M.p: 158 - 160℃M.p .: 158-160 ° C
1H NMR (300 MHz, DMSO) δ 8.24 (1H, t, J=5.6Hz), 7.30 (2H, m), 7.05 (1H, s), 6.85 (2H, m), 4.70 (2H, d, J=5.6Hz), 3.98 (2H, q, J=6.9), 3.89 (3H, s), 3.76 (6H, s), 3.71 (3H, s), 1.31 (3H, t, J=6.9Hz)(1H, d, J = 7.6 Hz), 7.30 (2H, m), 7.05 (1H, s), 6.85 S), 3.71 (3H, s), 1.31 (3H, t, J = 6.9Hz)
마지막으로 상온에서 acetone (20 mL) 중 교반된 용액 N-(6-Ethoxy-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine (885.8 mg, 1.95 mmol)에 H2SO4 160 μl, H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔 상(ethyl acetate :n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 87.6%(724.7mg).Finally, a solution of N- (6-Ethoxy-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methyl ] amine (885.8 mg, 1.95 mmol), 160 μl of H 2 SO 4, 4 mL of H 2 O and 203.2 mg (1.95 mmol) of CrO 3 were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 87.6% (724.7 mg).
M.p: 166 - 168℃M.p .: 166 - 168 ° C
1H NMR (200 MHz, DMSO) δ 8.33 (1H, s), 7.61 (1H, s), 7.28 (2H, m), 6.81 (3H, m), 4.68 (2H, s), 3.96 (2H, q, J=7.0Hz), 3.83 (3H, s), 3.79 (3H, s), 1.30 (3H, t, J=7.0Hz)
(1H, s), 7.28 (2H, m), 6.81 (3H, m), 4.68 (2H, s), 3.96 J = 7.0 Hz), 3.83 (3H, s), 3.79 (3H, s), 1.30 (3H, t,
1-65 NQ16 -3. 2-{[6- Ethoxy -1,3- benzothiazol -2- yl ) amino ] methyl }-5,8-dimethoxy-1,4-dihydro-1,4-naphthalenedione 1-65 NQ16 -3. 2 - {[6- Ethoxy -1,3- benzothiazol -2- yl ) amino ] methyl } -5,8- dimethoxy- 1,4-dihydro- 1,4-naphthalenedione
5℃에서 acetonitrile (15 mL) 중 교반된 용액 N-(6-Ethoxy-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine (885.8 mg, 2 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔 상(ethyl acetate :n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 52.9% (437.6 mg).(6-Ethoxy-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine (885.8 mg, 2 mmol) was added a solution of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in 3.5 mL water. The reaction was stirred at ambient temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 52.9% (437.6 mg).
M.p: 117 - 119℃M.p .: 117 - 119 캜
1H NMR (300 MHz, DMSO) δ 8.17 (1H, t, J=5.6Hz), 7.52 (2H, s), 7.38 (2H, m), 6.79 (1H, dd, J=8.6 and 2.4Hz), 6.56 (1H, s), 4.41 (2H, s), 3.97 (2H, q, J=7.0Hz), 3.86 (3H, s), 3.82 (3H, s), 1.30 (3H, t, J=7.0Hz)
(1H, d, J = 8.6 and 2.4 Hz), 6.56 (2H, s), 7.32 (1H, s), 4.41 (2H, s), 3.97 (2H, q, J = 7.0 Hz), 3.86 (3H, s), 3.82
1-66 NQ17 -4. 6-{[(6- Nitro -1,3- benzothiazol -2- yl ) amino ] methyl }-5,8-dimethoxy-1,4-dihydro-1,4-naphthalenedione 1-66 NQ17 -4. 6 - {[(6- nitro -1,3- benzothiazol -2- yl ) amino ] methyl } -5,8- dimethoxy- 1,4-dihydro-1,4- naphthalenedione
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-6-nitrobenzothiazole (1.42 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 3.02g (Yield: 91.9%)의 N-(6-Nitro-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl)methylidene]amine을 수득하였다.20 mL of 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol) and 2-Amino-6-nitrobenzothiazole were added to 100 mL of a round flask equipped with a Dean-Stark trap and a condenser. (1.42 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5) were added and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature, the reaction mixture was washed successively with 5% HCl, saturated NaHCO3, 5% acetic acid and water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl acetate and hexane to give 3.02 g (Yield: 91.9%) of N- (6-Nitro-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy -2-naphthyl) methylidene] amine.
M.p: 240 - 241℃M.p .: 240-241 ° C
1H NMR (200 MHz, CDCl3) δ 9.53 (1H, s), 8.76 (1H, d, J=2.4Hz), 8.34 (1H, dd, J=9.0 and 2.4Hz), 8.05 (1H, d, J=9.0Hz), 7.60 (1H, s), 7.06 (1H, d, J=8.8Hz), 6.95 (1H, d, J=8.8Hz), 4.05 (3H, s), 4.01 (3H, s), 3.93 (6H, s)
D, J = 9.0 and 2.4 Hz), 8.05 (1H, d, J = 2.4 Hz), 8.34 (1H, d, J = D, J = 8.8 Hz), 4.05 (3H, s), 4.01 (3H, s), 3.93 (6H, s)
이후 상온에서 tetrahydrofuran 30mL 중 교반된 용액인 N-(6-Nitro-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl) methylidene] amine (2.22 g, 4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 2.17 g (Yield: 97.5%)의 N-(6-Nitro-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl)methyl]amine을 수득하였다.Then, a solution of N- (6-Nitro-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methylidene] amine 2.22 g, 4.90 mmol) was slowly added LiAlH4 (195.7 mg, 4.90 mmol) over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The resulting product was recrystallized from ethyl ether to obtain 2.17 g (Yield: 97.5%) of N- (6-Nitro-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy- naphthyl) methyl] amine.
M.p: 222 - 223℃M.p .: 222 - 223 ° C
1H NMR (200 MHz, CDCl3) δ 8.41 (1H, d, J=2.4Hz), 8.04 (1H, dd, J=9.0 and 2.4Hz), 7.32 (1H, d, J=9.0Hz), 6.84 (3H, s), 4.81 (2H, s), 3.95 (3H, s), 3.88 (3H, s), 3.79 (3H, s)
Dd, J = 9.0 and 2.4 Hz), 7.32 (1H, d, J = 9.0 Hz), 6.84 (3H s), 4.81 (2H, s), 3.95 (3H, s), 3.88
마지막으로 상온에서 acetone (20 mL) 중 교반된 용액 N-(6-Nitro-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine (887.7 mg, 1.95 mmol)에 H2SO4 160 μl, H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔 상(ethyl acetate :n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 75.8% (628.5 mg).Finally, a solution of N- (6-Nitro-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methyl ] amine (887.7 mg, 1.95 mmol), 160 μl of H 2 SO 4, 4 mL of H 2 O and 203.2 mg (1.95 mmol) of CrO 3 were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 75.8% (628.5 mg).
M.p: 209 - 210℃M.p .: 209-210 ° C
1H NMR (200 MHz, DMSO) δ 9.22 (1H, s), 8.72 (1H, s), 8.11 (1H, d, J=8.8Hz), 7.60 (1H, s), 7.48 (1H, d, J=8.8Hz), 6.81 (2H, s), 4.76 (2H, s), 3.82 (3H, s), 3.76 (3H, s)
D, J = 8.8 Hz), 7.60 (1H, s), 7.48 (1H, s), 8.72 (1H, s) S), 3.76 (3H, s), 3.76 (2H, s)
1-67 NQ17 -3. 2-{[(6- Nitro -1,3- benzothiazol -2- yl ) amino ] methyl }-5,8-dimethoxy-1,4-dihydro-1,4-naphthalenedione 1-67 NQ17 -3. 2 - {[(6- Nitro -1,3- benzothiazol -2- yl ) amino ] methyl } -5,8- dimethoxy- 1,4-dihydro-1,4-naphthalenedione
5℃에서 acetonitrile (15 mL) 중 교반된 용액 N-(6-Nitro-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine (887.7 mg, 2 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔 상(ethyl acetate :n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다.Yield: 52.9% (437.6 mg).2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methyl] piperidine in acetonitrile (15 mL) amine (887.7 mg, 2 mmol) was added a solution of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in 3.5 mL water. The reaction was stirred at ambient temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 52.9% (437.6 mg).
M.p: 210℃M.p .: 210 DEG C
1H NMR (200 MHz, DMSO) δ 9.06 (1H, t, J=5.6Hz), 8.72 (1H, d, J=2.2Hz), 8.08 (1H, dd, J=9.0Hz and 2.2Hz), 7.54 (2H, s), 7.46 (1H, d, J=9.0Hz), 4.50 (2H, s), 3.85 (3H, s), 3.81 (3H, s)
(1H, d, J = 9.0 Hz and 2.2 Hz), 7.54 (1H, d, J = 2.2 Hz) (2H, s), 7.46 (1H, d, J = 9.0Hz), 4.50
1-68 NQ18 -4. 6-{[(6- Fluoro -1,3- benzothiazol -2- yl ) amino ] methyl }-5,8-dimethoxy-1,4-dihydro-1,4-naphthalenedione 1-68 NQ18 -4. 6 - {[(6- Fluoro -1,3- benzothiazol -2- yl ) amino ] methyl } -5,8- dimethoxy- 1,4-dihydro-1,4-naphthalenedione
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-6-fluorobenzothiazole (1.22 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 2.78 g (Yield: 89.9%)의 N-(6-Fluoro-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl)methylidene]amine을 수득하였다.20 mL of 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol) and 2-Amino-6-fluorobenzothiazole (20 mL) were added to 100 mL of a round flask equipped with a Dean- (1.22 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5) was added and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature, the reaction mixture was washed successively with 5% HCl, saturated NaHCO3, 5% acetic acid and water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The resulting product was recrystallized from ethyl acetate and hexane to give 2.78 g (Yield: 89.9%) of N- (6-Fluoro-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy -2-naphthyl) methylidene] amine.
M.p: 161 - 163℃M.p .: 161 - 163 ° C
1H NMR (200 MHz, CDCl3) δ 9.44 (1H, s), 7.94 (1H, m), 7.65 (1H, s), 7.53 (1H, dd, J=8.2 and 2.6Hz), 7.21 (1H, td, J=9.0Hz and 2.6Hz), 7.04 (1H, d, J=8.8Hz), 6.94 (1H, d, J=8.8Hz), 4.05 (3H, s), 4.00 (3H, s), 3.93 (3H, s), 3.92 (3H, s)(1H, s), 7.51 (1H, s), 7.53 (1H, dd, J = 8.2 and 2.6 Hz), 7.21 (1H, d, J = 8.8 Hz), 4.05 (3H, s), 4.00 (3H, s), 3.93 , < / RTI > s), 3.92 (3H, s)
이후 상온에서 tetrahydrofuran 30mL 중 교반된 용액인 N-(6-fluoro-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl) methylidene] amine (2.09 g, 4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 1.86 g (Yield: 88.4%)의 N-(6-Fluoro-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl)methyl]amine을 수득하였다After that, a solution of N- (6-fluoro-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methylidene] amine 2.09 g, 4.90 mmol) was slowly added LiAlH4 (195.7 mg, 4.90 mmol) over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The resulting product was recrystallized from ethyl ether to obtain 1.86 g (yield: 88.4%) of N- (6-Fluoro-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy- naphthyl) methyl] amine < / RTI >
M.p: 165 - 166℃M.p .: 165 - 166 ° C
1H NMR (200 MHz, CDCl3) δ 7.40 (1H, m), 7.25 (1H, dd, J=8.2 and 2.6Hz), 6.94 (1H, td, J=9.0 and 2.6Hz), 6.93 (1H, s), 6.84 (2H, s), 6.26 (1H, s), 4.79 (2H, s), 3.96 (3H, s), 3.98 (3H, s), 3.86 (3H, s), 3.81 (3H, s)
6.94 (1H, s), 6.94 (1H, td, J = 9.0 and 2.6 Hz), 6.93 (1H, s) , 6.84 (2H, s), 3.84 (2H, s), 3.84 (2H, s)
마지막으로 상온에서 acetone (20 mL) 중 교반된 용액 N-(6-Fluoro-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine (835.7 mg, 1.95 mmol)에 H2SO4 160 μl, H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔 상(ethyl acetate :n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 80.8% (627.9 mg)Finally, a solution of N- (6-Fluoro-1,3-benzothiazol-2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methyl ] amine (835.7 mg, 1.95 mmol), 160 μl of H 2 SO 4, 4 mL of H 2 O and 203.2 mg (1.95 mmol) of CrO 3 were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 80.8% (627.9 mg)
M.p: 134 - 135℃M.p .: 134-135 ° C
1H NMR (200 MHz, DMSO) δ 8.53 (1H, t, J=5.6Hz), 7.6 (2H, m), 7.38 (1H, m), 7.03 (1H, td, J=9.2 and 2.6Hz), 6.80 (2H, s), 4.67 (2H, d, J=5.6Hz), 3.80 (3H, s), 3.76 (3H, s)
(2H, m), 7.38 (1H, m), 7.03 (1H, td, J = 9.2 and 2.6 Hz), 6.80 (2H, s), 4.67 (2H, d, J = 5.6Hz), 3.80 (3H, s), 3.76
1-69 NQ18 -3. 2-{[(6- Fluoro -1,3- benzothiazol -2- yl ) amino ] methyl }-5,8-dimethoxy-1,4-dihydro-1,4-naphthalenedione 1-69 NQ18 -3. 2 - {[(6- Fluoro -1,3- benzothiazol -2- yl ) amino ] methyl } -5,8- dimethoxy- 1,4-dihydro-1,4-naphthalenedione
5℃에서 acetonitrile (15 mL) 중 교반된 용액 N-(6-Fluoro-1,3-benzothiazol-2-yl)-N-[(1,4,5,8-tetramethoxy-2-naphthyl) methyl] amine (835.7 mg, 1.95 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔 상(ethyl acetate :n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 72.1% (560.3 mg).2-yl) -N - [(1,4,5,8-tetramethoxy-2-naphthyl) methyl] piperidine in acetonitrile (15 mL) amine (835.7 mg, 1.95 mmol) was added a solution of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in 3.5 mL water. The reaction was stirred at ambient temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 72.1% (560.3 mg).
M.p: 181 - 182℃M.p .: 181-182 ° C
1H NMR (200 MHz, DMSO) δ 8.37 (1H, t, J=5.6Hz), 7.55 (2H, m), 7.33 (1H, m), 7.03 (1H, td, J=9.2 and 2.6Hz), 6.53 (1H, s), 4.40 (2H, s), 3.84 (3H, s), 3.80 (3H, s)
(2H, m), 7.33 (1H, m), 7.03 (1H, td, J = 9.2 and 2.6 Hz), 6.53 (1H, s), 4.40 (2H, s), 3.84 (3H, s), 3.80
1-70 NQ19 -4. 5,8- Dimethoxy -6-[(5- nitro - thiazol -2- ylamino )- methyl ]-[1,4]naphthoquinone 1-70 NQ19 -4. 5,8- Dimethoxy -6 - [(5- nitro - thiazol -2- ylamino) - methyl] - [1,4] naphthoquinone
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-5-nitrothiazole (1.16 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 2.78 g (Yield: 87.9%)의 (5-Nitro-thiazol-2-yl)-(1,4,5,8-tetramethoxy-naphthalen-2-ylmethylene)-amine을 수득하였다20 mL of 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol) and 2-Amino-5-nitrothiazole were added to 100 mL of a round flask equipped with a Dean-Stark trap and a condenser. (1.16 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5) and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature, the reaction mixture was washed successively with 5% HCl, saturated NaHCO3, 5% acetic acid and water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The resulting product was recrystallized from ethyl acetate and hexane to obtain 2.78 g (Yield: 87.9%) of (5-Nitro-thiazol-2-yl) - (1,4,5,8-tetramethoxy-naphthalen- Lt; / RTI >
1H NMR (300 MHz, CDCl3) δ 9.0 (1H, s), 8.5 (1H, s), 7.5 (1H, s), 6.1 (1H, d, J=9.3Hz), 5.9 (1H, d, J=9.3Hz), 4.7 (2H, d, J=5.3Hz), 4.0 (12H, s)
(1H, s), 7.5 (1H, s), 6.1 (1H, d, J = 9.3 Hz), 5.9 9.3 Hz), 4.7 (2H, d, J = 5.3 Hz), 4.0 (12H, s)
이후 상온에서 tetrahydrofuran 30mL 중 교반된 용액인 (5-Nitro-thiazol-2-yl)-(1,4,5,8-tetramethoxy-naphthalen-2-ylmethyl)-amine (1.97 g, 4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 1.86 g (Yield: 77.4%)을 수득하였다.Then, 5-Nitro-thiazol-2-yl- (1,4,5,8-tetramethoxy-naphthalen-2-ylmethyl) -amine (1.97 g, 4.90 mmol) in 30 mL of tetrahydrofuran at room temperature was added with LiAlH4 (195.7 mg, 4.90 mmol) was slowly added over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl ether to give 1.86 g (Yield: 77.4%).
1H NMR (300 MHz, CDCl3) δ 10.5 (1H, s), 7.7 (1H, s), 6.8 (2H, s), 4.7 (2H, d, J=5.3Hz), 4.0 (6H, s)
(1H, s), 6.8 (2H, s), 4.7 (2H, d, J = 5.3 Hz), 4.0 (6H, s)
마지막으로 상온에서 acetone (20 mL) 중 교반된 용액 NQ19-2A (786.74 mg, 1.95 mmol)에 H2SO4 160 μl, H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 ethyl ether에 의해 화합물을 분리하였다. 결과물을 에틸 아세테이트 및 n-hexan으로부터 재결정화하였다. Yield: 80.8% (635.6 mg).Finally, 160 μl of H2SO4, 4 mL of H2O and 203.2 mg (1.95 mmol) of CrO3 were added to the stirred solution of NQ19-2A (786.74 mg, 1.95 mmol) in acetone (20 mL) at room temperature. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. acetone and ethyl ether. The result was recrystallized from ethyl acetate and n-hexane. Yield: 80.8% (635.6 mg).
1H NMR (300 MHz, CDCl3) δ 10.5 (1H, s), 7.7 (1H, s), 6.8 (2H, s), 4.7 (2H, d, J=5.3Hz), 4.0 (6H, s)
(1H, s), 6.8 (2H, s), 4.7 (2H, d, J = 5.3 Hz), 4.0 (6H, s)
1-71 NQ19 -3. 5,8- Dimethoxy -2-[(5- nitro - thiazol -2- ylamino )- methyl ]-[1,4]naphthoquinone 1-71 NQ19 -3. 5,8- Dimethoxy -2 - [(5- nitro - thiazol -2- ylamino) - methyl] - [1,4] naphthoquinone
5℃에서 acetonitrile (15 mL) 중 교반된 용액 (5-Nitro-thiazol-2-yl)-(1,4,5,8-tetramethoxy-naphthalen-2-ylmethyl)-amine (786.74 mg, 1.95 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 에틸 아세테이트 및 n-hexan으로부터 재결정화하였다. Yield: 72.1% (560.3 mg).5-Nitro-thiazol-2-yl) - (1,4,5,8-tetramethoxy-naphthalen-2- ylmethyl) -amine (786.74 mg, 1.95 mmol) in acetonitrile (15 mL) Was added a solution of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in 3.5 mL of water. The reaction was stirred at ambient temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The result was recrystallized from ethyl acetate and n-hexane. Yield: 72.1% (560.3 mg).
1H NMR (300 MHz, CDCl3) δ 9.5 (1H, s), 8.5 (1H, s), 7.5 (1H, s), 6.1 (1H, d, J=9.3Hz), 5.9 (1H, d, J=9.3Hz), 4.0 (12H,s)
D, J = 9.3 Hz), 5.9 (1H, s), 7.5 (1H, s), 7.5 9.3 Hz), 4.0 (12H, s)
1-72 NQ20 -4. C-{4-[(1,4- Dimethoxy -5,8- dioxo -5,8- dihydro - naphthalen -2-ylmethyl)-amino]-phenyl}-N-methyl-methanesulfonamide 1-72 NQ20 -4. C- {4 - [(1,4- Dimethoxy -5,8- dioxo -5,8- dihydro - naphthalen -2- ylmethyl) -amino] -phenyl} -N-methyl-methanesulfonamide
딘스타크 트랩(Dean-Stark trap) 및 냉각기가 달린 둥근 플라스크 100 mL에 벤젠 20 mL, 2-Formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-N-methyl-α-toluensulfonamide (1.45 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5)을 첨가하고, 혼합물을 20h동안 환류시켰다. 그 후, 공비증류(azeotropic distillation)에 의해 물을 제거하였다. 실온까지 냉각시킨 다음, 반응 혼합물을 연속으로 5% HCL, 포화된 NaHCO3, 5% 아세트산 및 물로 세척하였다. 유기물 층을 MgSO4로 건조시키고 감압 하에서 농축시켰다. 결과물을 에틸 아세테이트 및 hexan으로부터 재결정화하여 3 g (Yield: 87%)의 N-Methyl-C-{4-[(1,4,5,8-tetramethoxy-naphthalen-2-ylmethylene)-amino]-phenyl}-methanesulfonamide을 수득하였다.20 mL of 2-formyl-1,4,5,8-tetramethoxynaphthalene (2 g, 7.25 mmol), 2-Amino-N-methyl (1.45 g, 7.25 mmol), triethylamine (1.03 mL, 7.25 mmol), acetic acid (300 μl, pH 4-5) was added and the mixture was refluxed for 20 h. The water was then removed by azeotropic distillation. After cooling to room temperature and washed, and then the reaction mixture is continuously 5% HCL, saturated NaHCO 3, 5% acetic acid and water. Dry the organic layer with MgSO 4 and concentrated under reduced pressure. The resultant was recrystallized from ethyl acetate and hexane to give 3 g (Yield: 87%) of N-Methyl-C- {4 - [(1,4,5,8-tetramethoxy-naphthalen- 2- ylmethylene) phenyl} -methanesulfonamide.
1H NMR (300 MHz, CDCl3) δ 9.0 (1H, s), 7.6 (1H, s), 7.5 (2H, d, J=9.3Hz), 7.3 (1H, s), 7.0 (2H, d, J=9.3Hz), 4.3 (1H, s), 4.0 (12H, s), 2.7 (3H, d, J=6)
(1H, s), 7.5 (2H, d, J = 9.3 Hz), 7.3 (1H, s), 7.0 4.3 (1H, s), 2.7 (3H, d, J = 6)
이후 상온에서 tetrahydrofuran 30mL 중 교반된 용액인 N-Methyl-C-{4-[(1,4,5,8-tetramethoxy-naphthalen-2-ylmethylene)-amino]-phenyl}-methanesulfonamide (2.24 g, 4.90 mmol)에 LiAlH4 (195.7 mg, 4.90 mmol)를 10분에 걸쳐 천천히 첨가하였다. 혼합물을 상온에서 30분 동안 교반하였다. 상기 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 ethyl ether로부터 재결정하여 1.68 g (Yield: 75%)의 N-Methyl-C-{4-[(1,4,5,8-tetramethoxy-naphthalen-2-ylmethyl)-amino]-phenyl}-methanesulfonamide을 수득하였다.Then, a solution of N-Methyl-C- {4- [(1,4,5,8-tetramethoxy-naphthalen-2-ylmethylene) -amino] -phenyl} -methanesulfonamide (2.24 g, 4.90 mmol) was slowly added LiAlH 4 (195.7 mg, 4.90 mmol) over 10 minutes. The mixture was stirred at room temperature for 30 minutes. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The resulting product was recrystallized from ethyl ether to obtain 1.68 g (Yield: 75%) of N-Methyl-C- {4 - [(1,4,5,8-tetramethoxy-naphthalen- methanesulfonamide.
1H NMR (300 MHz, CDCl3) δ 9.0 (1H, s), 7.6 (1H, s), 7.5 (2H, d, J=9.3Hz), 7.3 (1H, s), 7.0 (2H, d, J=9.3Hz), 4.5 (2H, d, J=6.8), 4.3 (1H, s), 4.0 (12H, s), 2.7 (3H, d, J=6)(1H, s), 7.5 (2H, d, J = 9.3 Hz), 7.3 (1H, s), 7.0 S), 2.7 (3H, d, J = 6), 4.5 (2H, d, J =
마지막으로 상온에서 acetone (20 mL) 중 교반된 용액 N-Methyl-C-{4-[(1,4,5,8-tetramethoxy-naphthalen-2-ylmethyl)-amino]-phenyl}-methanesulfonamide (897 mg, 1.95 mmol)에 H2SO4 160 μl, H2O 4 mL, CrO3 203.2 mg (1.95 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. acetone 및 ethyl ether에 의해 화합물을 분리하였다. 결과물을 에틸 아세테이트 및 n-hexan으로부터 재결정화하였다. Yield: 80% (717.6 mg)Finally, a stirred solution of N-Methyl-C- {4 - [(1,4,5,8-tetramethoxy-naphthalen-2-ylmethyl) -amino] -phenyl} -methanesulfonamide (897 mg, 1.95 mmol), 160 μl of H 2 SO 4, 4 mL of H 2 O and 203.2 mg (1.95 mmol) of CrO 3 were added. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. acetone and ethyl ether. The result was recrystallized from ethyl acetate and n-hexane. Yield: 80% (717.6 mg)
1H NMR (300 MHz, CDCl3) δ 7.5 (1H, s), 7.3 (2H, d, J=9.3Hz), 6.9 (2H, d, J=10.6Hz), 6.6 (2H, d, J=10.6Hz), 4.5 (2H, d), 4.0 (6H, s), 2.6 (3H, d, J=10.5Hz)
D, J = 9.3 Hz), 6.9 (2H, d, J = 10.6 Hz), 6.6 (2H, d, J = 10.6 Hz, 1H) ), 4.5 (2H, d), 4.0 (6H, s), 2.6 (3H, d, J =
1-73 NQ20-3. C-{4-[(5,8-Dimethoxy-1,4-dioxo-1,4-dihydro-naphthalen-2-ylmethyl)-amino]-phenyl}-N-methyl-methanesulfonamide1-73 NQ20-3. C- {4 - [(5,8-Dimethoxy-1,4-dioxo-1,4-dihydro-naphthalen-2-ylmethyl) -amino] -phenyl} -N-methyl-methanesulfonamide
5℃에서 acetonitrile (15 mL) 중 교반된 용액 N-Methyl-C-{4-[(1,4,5,8-tetramethoxy-naphthalen-2-ylmethyl)-amino]-phenyl}-methanesulfonamide (897 mg, 1.95 mmol)에 3.5mL water 중 ammonium cerium(IV) nitrate(2.72 g, 4.87 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 결과물을 에틸 아세테이트 및 n-hexan으로부터 재결정화하였다.Yield: 70% (627.9 mg).A stirred solution of N-Methyl-C- {4 - [(1,4,5,8-tetramethoxy-naphthalen-2-ylmethyl) -amino] -phenyl} -methanesulfonamide (897 mg, , 1.95 mmol) was added a solution of ammonium cerium (IV) nitrate (2.72 g, 4.87 mmol) in 3.5 mL water. The reaction was stirred at ambient temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO 4 and concentrated under reduced pressure. The product was recrystallized from ethyl acetate and n-hexane. Yield: 70% (627.9 mg).
1H NMR (300 MHz, DMSO) δ 7.5 (1H, s), 7.6 (1H, s), 7.1 (2H, d, J=9.3Hz), 6.7 (1H, d), 6.6 (2H, d, J=10.6Hz), 4.3 (2H, d), 4.0 (6H, s), 2.6 (3H, d, J=10.5Hz)
(1H, s), 7.1 (2H, d, J = 9.3 Hz), 6.7 (1H, d), 6.6 D), 4.0 (6H, s), 2.6 (3H, d, J = 10.5 Hz)
1-74 NQ22 -4. 2-( Methoxyiminomethyl )-1,4- dimethoxy -5,8- dihydro -5,8-naphthalenedione 1-74 NQ22-4 . 2- (Methoxyiminomethyl) -1,4- dimethoxy -5,8- dihydro -5,8- naphthalenedione
100 mL 둥근 바닥 플라스크에 2-Formyl-1,4,5,8-tetramethoxynaphthalene (5.52 g, 20 mmol), NH2OH.HCl (1.67 g, 24 mmol) 및, ethyl alcohol과 water (1:1) 100 mL를 첨가하였다. 반응 혼합물을 상온에서 2시간 동안 교반하였다. TLC 체크 후에, 반응물을 800 mL water 및 500 mL ethyl ether로 3회 추출하였다.실리카겔 상(ethyl acetate:n-hexan=1:4) 칼럼 크로마토그래피에 의해 2-(hydroxyiminomethyl)-1,4,5,8-tetramethoxynaphthalene 화합물을 분리하였다. Yield: 88% (5.31 g)To a 100 mL round bottom flask was added 2-Formyl-1,4,5,8-tetramethoxynaphthalene (5.52 g, 20 mmol), NH2OH.HCl (1.67 g, 24 mmol) and ethyl alcohol and water (1: Was added. The reaction mixture was stirred at room temperature for 2 hours. After TLC check, the reaction product was extracted three times with 800 mL of water and 500 mL of ethyl ether. Column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4) gave 2- (hydroxyiminomethyl) , 8-tetramethoxynaphthalene. Yield: 88% (5.31 g)
Mp: 145 - 146℃Mp: 145 - 146 캜
1H-NMR (300Hz, DMSO) δ 8.65 (1H, s), 7.90 (1H, s), 7.21 (1H, s), 6.92 (1H, d, J=8.7Hz), 6.92 (1H, d, J=8.7Hz), 6.88 (1H, d, J=8.7Hz), 3.96 (6H, s), 3.91 (3H, s), 3.79 (1H, s)
D, J = 8.7 Hz), 6.92 (1H, s), 7.92 (1H, s), 7.21 (1H, s), 3.91 (3H, s), 3.79 (1H, s)
우선 상온에서 100 mL 둥근 바닥 플라스크에 2-(hydroxyiminomethyl)-1,4,5,8-tetra methoxynaphthalene (528 mg, 2 mmol), THF 10 mL를 첨가하였다. 반응물을 교반하고 10분 동안 NaH (62 mg, 2.6 mmol)를 천천히 첨가하였다. 그 후, 반응 혼합물에 methyl iodide (162 μl, 2.6 mmol)를 넣고 약 6시간 동안 교반하였다. TLC 체크 후에, 반응물을 50 mL water 및 50 mL methylene chloride로 2회 추출하였다.실리카겔 상(ethyl acetate:n-hexan=1:4) 칼럼 크로마토그래피에 의해 2-(Methoxyiminomethyl)-1,4,5,8-tetramethoxynaphthalene 화합물을 분리하였다. Yield: 90% (550 mg)First, 2- (hydroxyiminomethyl) -1,4,5,8-tetra methoxynaphthalene (528 mg, 2 mmol) and 10 mL of THF were added to a 100 mL round bottom flask at room temperature. The reaction was stirred and NaH (62 mg, 2.6 mmol) was added slowly for 10 min. Then, methyl iodide (162 μl, 2.6 mmol) was added to the reaction mixture and stirred for about 6 hours. After TLC check, the reaction product was extracted twice with 50 mL of water and 50 mL of methylene chloride. Column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4) gave 2- (Methoxyiminomethyl) , 8-tetramethoxynaphthalene. Yield: 90% (550 mg)
Mp: 114 - 116℃Mp: 114 - 116 ° C
1H-NMR (300Hz, DMSO) δ 8.84 (1H, s), 7.290(1H, s), 6.90 (1H, d, J=8.7Hz), 6.86 (1H, d, J=8.7Hz, 4.03 (3H, s), 3.99 (3H, s), 3.95 (3H, s), 3.90 (3H, s), 3.76 (3H, s)
D, J = 8.7 Hz, 4.03 (3H, s), 6.90 (1H, s), 6.90 s), 3.99 (3H, s), 3.95 (3H, s), 3.90
마지막으로 상온에서 acetone (20 mL) 중 교반된 용액 2-(Methoxyiminomethyl)-1,4,5,8-tetramethoxynaphthalene (305 mg,1 mmol)에 H2SO4 125 μl , H2O 385 μl, CrO3 150 mg (1.5 mmol)을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔 상(ethyl acetate:n-hexan=1:2) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 71% (196.3 mg).Finally, 125 μl of H2SO4, 385 μl of H2O and 150 mg of CrO3 (1.5 mmol) were added to the stirred solution of 2- (Methoxyiminomethyl) -1,4,5,8-tetramethoxynaphthalene (305 mg, 1 mmol) in acetone ). The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 2). Yield: 71% (196.3 mg).
M.p: 173 - 174℃M.p .: 173-174 ° C
1H-NMR (300Hz, CDCl3) δ 8.23 (1H, s), 7.80 (1H, s), 6.84 (1H, d, J=10.2Hz), 6.79 (1H, d, J=10.2Hz), 4.06 (3H, s), 4.03 (3H, s), 3.84 (3H, s)
(1H, d, J = 10.2 Hz), 6.79 (1H, d, J = 10.2 Hz), 4.06 (3H , s), 4.03 (3H, s), 3.84 (3H, s)
1-75 NQ22 -3. 2-( Methoxyiminomethyl )-5,8- dimethoxy -1,4- dihydro -1,4-naphthalenedione 1-75 NQ22 -3. 2- ( Methoxyiminomethyl ) -5,8- dimethoxy- 1,4- dihydro- 1,4- naphthalenedione
5℃에서 acetonitrile (15 mL) 중 교반된 용액 2-(Methoxyiminomethyl)-1,4,5,8-tetramethoxynaphthalene (305 mg, 1 mmol)에 4mL water 중 ammonium cerium(IV) nitrate (3.05 g, 1 mmol) 용액을 첨가하였다. 반응물을 상온에서 1시간 동안 교반하였다. 반응 혼합물을 methylene chloride로 추출하고 water로 세척하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔 상(ethyl acetate:n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 22% (60.8 mg)To a stirred solution of 2- (Methoxyiminomethyl) -1,4,5,8-tetramethoxynaphthalene (305 mg, 1 mmol) in acetonitrile (15 mL) at 5 ° C was added ammonium cerium (IV) nitrate (3.05 g, ) Solution. The reaction was stirred at ambient temperature for 1 hour. The reaction mixture was extracted with methylene chloride and washed with water. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 22% (60.8 mg)
M.p: 122 - 124℃M.p .: 122 - 124 캜
1H-NMR (300Hz, CDCl3) δ 8.26 (1H, s), 7.34 (2H, s), 7.20 (1H, s), 4.02 (3H, s), 4.03 (3H, s), 3.97 (6H,s)
(3H, s), 3.97 (6H, s), 4.02 (3H, s), 4.02 (3H, s)
1-76 1-76 NQ23NQ23 . 5,8-. 5,8- DimethoxyDimethoxy -2--2- methoxyaminomethoxyamino -[1,4]- [1, 4] naphthoquinonenaphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 NH2OH.HCl (144 mg, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:4) 에 의해 정제하여 생성물을 얻었다(1 mmol, 261.28 mg). 상기 생성물을 THF (5 mL)에 용해하고 NaH (1.3 mmol, 62 mg)를 천천히 첨가하였다. 반응 혼합물을 상온에서 10분 동안 교반하였다. 그 후, 반응물에 CH3I (1.3 mmol, 81 μl)를 첨가하고 6시간 동안 200℃에서 가열하였다. 냉각 후, 반응 혼합물에 물을 첨가하고, 50 mL water 및 50 mL methylene chloride로 추출하였다. 유기층을 MgSO4로 건조하고 감압 하 농축하였다. 실리카겔 상(ethyl acetate:n-hexan=1:4) 칼럼 크로마토그래피에 의해 화합물을 분리하였다. Yield: 63.6% (164.6 mg)NH2OH.HCl (144 mg, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 4) to give the product (1 mmol, 261.28 mg). The product was dissolved in THF (5 mL) and NaH (1.3 mmol, 62 mg) was slowly added. The reaction mixture was stirred at ambient temperature for 10 minutes. CH3I (1.3 mmol, 81 [mu] l) was then added to the reaction and heated at 200 [deg.] C for 6 hours. After cooling, water was added to the reaction mixture and extracted with 50 mL water and 50 mL methylene chloride. The organic layer was dried over MgSO4 and concentrated under reduced pressure. The compound was isolated by column chromatography on silica gel (ethyl acetate: n-hexane = 1: 4). Yield: 63.6% (164.6 mg)
1H-NMR (300Hz, CDCl3) δ 7.5 (2H, d, J=11Hz), 6.0 (1H, s), 3.9 (6H, s), 3.7 (3H, s)
(1H, s), 3.9 (6H, s), 3.7 (3H, s), 7.5 (2H, d, J =
1-77 NQ24 . 2-(4- Hydroxy - cyclohexylamino )-5,8- dimethoxy -[1,4]naphthoquinone 1-77 NQ24 . 2- (4- Hydroxy - cyclohexylamino) -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 trans-4-Aminocyclohexanol(238.48 mg, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:4) 에 의해 정제하여 생성물을 얻었다. Yield: 83.6% (382.3 mg)4-Aminocyclohexanol (238.48 mg, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 4) to give the product. Yield: 83.6% (382.3 mg)
1H-NMR (300Hz, CDCl3) δ 7.48 (1H, d, J=10.3Hz), 7.42 (1H, d, J=10.3Hz), 5.6 (1H, s), 4.0 (6H, s), 3.7 (1H, m), 3.3 (1H, m), 2.0 (4H, m, J=6.8Hz)
(1H, s), 3.7 (1H, s), 7.4 (1H, d, J = 10.3Hz) , m), 3.3 (1 H, m), 2.0 (4H, m, J = 6.8 Hz)
1-78 1-78 NQ25NQ25 . 2-(. 2-( IndanIndan -2--2- ylaminoylamino )-5,8-) -5,8- dimethoxydimethoxy -[1,4]- [1, 4] naphthoquinonenaphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 2-Aminoindan (275.7 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:2) 에 의해 정제하여 생성물을 얻었다. Yield: 30% (144.6 mg)2-Aminoindan (275.7 μL, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 2) to give the product. Yield: 30% (144.6 mg)
1H-NMR (300Hz, DMSO) δ 7.5 (2H, d, J=10.3Hz), 7.4 (1H, d, J=10.3Hz), 7.2 (2H, d, J=6Hz), 7.15 (2H, d, J=6Hz), 7.0 (1H, d, J=7.7Hz), 5.0 (1H, s), 4.2 (1H, q, J=6.8Hz), 3.8 (6H, s), 3.25 (2H, d, J=8.3Hz), 3.0 (1H, d, J=6.3Hz)
D, J = 10.3 Hz), 7.2 (2H, d, J = 6 Hz), 7.15 (2H, d, J = J = 6 Hz), 7.0 (1H, d, J = 7.7 Hz), 5.0 (1H, s), 4.2 = 8.3 Hz), 3.0 (1H, d, J = 6.3 Hz)
1-79 1-79 NQ26NQ26 . 2-(4-. 2- (4- AminoAmino -- phenylaminophenylamino )-5,8-) -5,8- dimethoxydimethoxy -[1,4]- [1, 4] naphthoquinonenaphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 1,4-Diphenylene diamine (248.7 mg, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:2) 에 의해 정제하여 생성물을 얻었다. Yield: 53.2% (233 mg)1,4-Diphenylene diamine (248.7 mg, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 2) to give the product. Yield: 53.2% (233 mg)
1H-NMR (300Hz, CDCl3) δ 7.4 (1H, d, J=10.6Hz), 7.35 (1H, d, J=10.6Hz), 7.0 (1H, d, J=9.7Hz), 6.7 (1H, d, J=9.7Hz), 6.1 (1H, s), 5.4 (1H, s), 4.0(6H, s)
(1H, d, J = 9.7 Hz), 6.7 (1H, d, J = 10.6 Hz) , J = 9.7 Hz), 6.1 (1H, s), 5.4 (1H, s), 4.0 (6H, s)
1-80 NQ27 . 2-(3- Cyclohexylamino - propylamino )-5,8- dimethoxy -[1,4]naphthoquinone 1-80 NQ27 . 2- (3- Cyclohexylamino - propylamino) -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 N-(3-Aminopropyl cyclohexyl amine) (351.6 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:4) 에 의해 정제하여 생성물을 얻었다. Yield: 52.5% (270 mg).(3-Aminopropyl cyclohexyl amine) (351.6 μL, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 4) to give the product. Yield: 52.5% (270 mg).
1H-NMR (300Hz, CDCl3) δ 7.2 (2H, d, J=8Hz), 5.8 (1H, s), 4.0 (6H, s), 3.4 (2H, m), 1.8 (2H, m), 1.5 (11H, m), 1.0 (2H, t, J=9.8Hz)
1.5 (2H, m), 1.5 (1H, s), 4.0 (6H, s), 3.4 11H, m), 1.0 (2H, t, J = 9.8 Hz)
1-81 1-81 NQ28NQ28 .. 5,8-5,8- DimethoxyDimethoxy -2-(3--2- (3- methylmethyl -- butylaminobutylamino )-[1,4]) - [1, 4] naphthoquinonenaphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 Isoamyl amine (240.5 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:4) 에 의해 정제하여 생성물을 얻었다. Yield: 67.7% (283.8 mg)Isoamyl amine (240.5 μL, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 4) to give the product. Yield: 67.7% (283.8 mg)
1H-NMR (300Hz, CDCl3) δ 7.4 (2H, d, J=10.6Hz), 7.25 (2H, d, J=10.6Hz), 5.7 (1H, s), 5.6 (1H, s), 4.0 (6H, s), 3.2 (2H, q, J=8.5Hz), 1.7 (2H, m), 1.5 (1H, m), 1.0 (6H, d, J=7.0Hz)
(2H, d, J = 10.6 Hz), 5.7 (1H, s), 5.6 (1H, s), 4.0 (6H (2H, m), 1.5 (1H, m), 1.0 (6H, d, J = 7.0Hz)
1-82 NQ29 . 2-[2-(2- Hydroxy - ethylamino )- ethylamino ]-5,8- dimethoxy -[1,4]naphthoquinone 1-82 NQ29 . 2- [2- (2- Hydroxy - ethylamino ) - ethylamino] -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 2-(2-Aminoethylamino) ethanol (209 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:4) 에 의해 정제하여 생성물을 얻었다. Yield: 38% (168.1 mg).2- (2-Aminoethylamino) ethanol (209 μL, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 4) to give the product. Yield: 38% (168.1 mg).
1H-NMR (300Hz, CDCl3) δ 7.5 (1H, d, J=10Hz), 7.2 (1H, d, J=10Hz), 5.6 (1H, s), 4.2 (2H, t), 4.0 (6H, s), 3.8 (2H, t), 3.6 (2H, q), 2.0 (2H,q)
(1H, d, J = 10 Hz), 5.6 (1H, s), 4.2 (2H, t), 4.0 (6H, s), 7.5 ), 3.8 (2H, t), 3.6 (2H, q), 2.0 (2H, q)
1-83 1-83 NQ30NQ30 . 2-. 2- BenzylaminoBenzylamino -5,8--5,8- dimethoxydimethoxy -[1,4]- [1, 4] naphthoquinonenaphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 Benzylamine (111 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:2) 에 의해 정제하여 생성물을 얻었다. Yield: 58.8% (262.6 mg).
Benzylamine (111 μl, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 2) to give the product. Yield: 58.8% (262.6 mg).
*1H-NMR (300Hz, CDCl3) δ 7.5 (7H, m), 6.0 (1H, s), 5.6 (1H, s), 4.4 (2H, d, 6.8Hz), 4.0 (6H, s)
(1H, s), 4.4 (2H, d, 6.8 Hz), 4.0 (6H, s)
1-84 1-84 NQ31NQ31 . 5,8-. 5,8- DimethoxyDimethoxy -2--2- piperidinpiperidine -1--One- ylyl -[1,4]- [1, 4] naphthoquinonenaphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 Piperidine (212.17 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:2) 에 의해 정제하여 생성물을 얻었다. Yield: 33.3% (138.6 mg)Piperidine (212.17 [mu] l, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 2) to give the product. Yield: 33.3% (138.6 mg)
1H-NMR (300Hz, CDCl3) δ 7.4 (1H, d, J=10.6Hz), 7.3 (1H, d, J=10.6Hz), 5.6 (1H, s), 4.0 (6H, s), 3.6 (2H, d, J=6Hz), 2.6 (2H, t), 1.3 (6H,m)
(1H, d, J = 10.6 Hz), 5.6 (1H, s), 4.0 (6H, s), 3.6 , d, J = 6 Hz), 2.6 (2H, t), 1.3 (6H, m)
1-85 NQ32 . 2-(1- Hydroxymethyl - propylamino )-5,8- dimethoxy -[1,4]naphthoquinone 1-85 NQ32 . 2- (1- Hydroxymethyl - propylamino) -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 (R)-(-)-2-Amino-1-butanol (194.8 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:4) 에 의해 정제하여 생성물을 얻었다. Yield: 67.6% (285.1 mg).(R) - (-) - 2-Amino-1-butanol (194.8 μl, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH Respectively. The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 4) to give the product. Yield: 67.6% (285.1 mg).
1H-NMR (300Hz, CDCl3) δ 7.4 (1H, d, J=10Hz), 7.3 (1H, d, J=10Hz), 5.7 (2H, s), 4.0 (6H, s), 3.7 (2H, d), 3.4 (1H, m), 2.5 (2H, m), 1.0 (3H, t, J=8.5Hz)
(1H, d, J = 10 Hz), 5.7 (2H, s), 4.0 (6H, s), 3.7 ), 3.4 (1H, m), 2.5 (2H, m), 1.0 (3H, t, J =
1-86 1-86 NQ33NQ33 . 2-(2-. 2- (2- ChloroChloro -- ethylaminoethylamino )-5,8-) -5,8- dimethoxydimethoxy -[1,4]- [1, 4] naphthoquinonenaphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 2-Chlorethylamin Hydrochlorid (160 mg, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:2) 에 의해 정제하여 생성물을 얻었다. Yield: 58.6% (239.2 mg)2-Chlorethylamine hydrochloride (160 mg, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 2) to give the product. Yield: 58.6% (239.2 mg)
1H-NMR (300Hz, CDCl3) δ 7.5 (1H, d, J=10.7Hz), 7.4 (1H, d, J=10.7Hz), 6.0 (1H, t), 5.8 (1H, s), 4.5 (2H, q, J=9Hz), 4.0 (6H, s), 3.5 (2H, t, J=7.0Hz)
(1H, s), 4.5 (2H, d, J = 10.7 Hz), 7.4 , q, J = 9 Hz), 4.0 (6H, s), 3.5 (2H, t,
1-87 NQ34 . 2-(2,4- Dimethoxy - benzylamino )-5,8- dimethoxy -[1,4]naphthoquinone 1-87 NQ34 . 2- (2,4- Dimethoxy - benzylamino) -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 2,4-Dimethoxybenzylamin hydrochlorid (421.6 mg, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:2) 에 의해 정제하여 생성물을 얻었다. Yield: 41.8% (206.2 mg).2,4-Dimethoxybenzylamine hydrochloride (421.6 mg, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL) The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 2) to give the product. Yield: 41.8% (206.2 mg).
1H-NMR (300Hz, CDCl3) δ 7.8 (1H, d, J=10Hz), 7.6 (1H, s), 7.5 (1H, d, J=10Hz), 6.5 (2h, d, J=8Hz), 5.8 (1H, s), 4.5 (2H, d, J=7.0Hz), 3.8 (6H, s), 3.6 (6H, s)
(1H, d, J = 8 Hz), 5.8 (1H, s), 7.5 (1H, (1H, s), 4.5 (2H, d, J = 7.0 Hz), 3.8 (6H,
1-88 NQ35 . 4-(5,8- Dimethoxy -1,4- dioxo -1,4- dihydro - naphthalen -2-ylamino)-piperidine-1-carboxylic acid ethyl ester 1-88 NQ35 . 4- (5,8- Dimethoxy- 1,4- dioxo- 1,4- dihydro - naphthalen -2- ylamino) -piperidine-1-carboxylic acid ethyl ester
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 Ethyl 4-amino-1-piperidinecarboxylate (356.04 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:2) 에 의해 정제하여 생성물을 얻었다. Yield: 54.6% (238.4 mg)Ethyl 4-amino-1-piperidinecarboxylate (356.04 μl, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 2) to give the product. Yield: 54.6% (238.4 mg)
1H-NMR (300Hz, CDCl3) δ 7.5 (1H, d, J=10.3Hz), 7.3 (1H, d, J=10.3Hz), 5.6 (1H, s), 4.3 (2H, q, J=8Hz), 2.1 (2H, t, J=8.7Hz), 1.5 (2H, t, J=8Hz), 1.3 (3H, t, J=7.3Hz)
(1H, s, J = 8 Hz), 7.3 (1H, d, J = 10.3 Hz) , 2.1 (2H, t, J = 8.7 Hz), 1.5 (2H, t, J = 8 Hz), 1.3 (3H,
1-89 NQ36 . 4-[2-(5,8- Dimethoxy -1,4- dioxo -1,4- dihydro - naphthalen -2-ylamino)-ethyl]-benzeensulfonamide 1-89 NQ36 . 4- [2- (5,8- Dimethoxy- 1,4- dioxo- 1,4- dihydro - naphthalen -2- ylamino) -ethyl] -benzenesulfonamide
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 4-(2-Aminoethyl) benzene sulphonamide (414.5 mg, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:2) 에 의해 정제하여 생성물을 얻었다. Yield: 90.7% (521.7 mg)4- (2-Aminoethyl) benzene sulphonamide (414.5 mg, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 2) to give the product. Yield: 90.7% (521.7 mg)
1H-NMR (300Hz, DMSO) δ 7.8 (2H, d, J=9.3Hz), 7.5 (4H, dd, J=10Hz), 7.3 (2H, s), 7.0 (1H, t), 5.5 (1H, s), 3.8 (6H, s), 3.0 (2H, t, J=8.5Hz), 2.5 (2H, t, J=8Hz)
7.5 (4H, dd, J = 10 Hz), 7.3 (2H, s), 7.0 (1H, t), 5.5 (1H, d, J = 9.3Hz) (2H, t, J = 8 Hz), 3.8 (6H, s), 3.0
1-90 1-90 NQ37NQ37 . 2-(4-. 2- (4- AminoAmino -- benzylaminobenzylamino )-5,8-) -5,8- dimethoxydimethoxy -[1,4]- [1, 4] naphthoquinonenaphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 4-Amino benzyl amine (252.89 mg, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:2) 에 의해 정제하여 생성물을 얻었다. Yield: 81.9% (382.8 mg)4-Amino benzyl amine (252.89 mg, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 2) to give the product. Yield: 81.9% (382.8 mg)
1H-NMR (300Hz, CDCl3) δ 7.4 (1H, d, J=10.3Hz), 7.3 (1H, d, J=10.3Hz), 7.1 (2H, d, J=9.3Hz), 6.7 (2H, d, J=9.3Hz), 5.6 (1H, s), 4.2 (2H, d, J=9.7Hz), 4.0 (6H, s), 3.7(1H, s), 2.2 (2H, s)
7.3 (1H, d, J = 10.3 Hz), 7.1 (2H, d, J = 9.3 Hz), 6.7 (2H, d, J = (1H, s), 2.2 (2H, s), 4.0 (6H, s)
1-91 NQ38 . 2-(1- Benzyl - piperidin -4- ylamino )-5,8- dimethoxy -[1,4]naphthoquinone 1-91 NQ38 . 2- (1- Benzyl - piperidin -4- ylamino ) -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 4-Amino-1-benzylpipeidine (394 mg, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:4) 에 의해 정제하여 생성물을 얻었다. Yield: 64.14% (359.8 mg)4-Amino-1-benzylpipeidine (394 mg, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 4) to give the product. Yield: 64.14% (359.8 mg)
1H-NMR (300Hz, CDCl3) δ 7.5 (5H, m), 7.3 (2H, d, J=10.3Hz), 5.65 (1H, d), 5.6 (1H, s), 4.0 (6H, s), 3.5 (2H, s), 3.4 (1H, m, J=8.7Hz), 2.7 (2H, d, J=9Hz), 2.3 (2H, t, J=9Hz), 2.0 (2H, d, J=9Hz)
(1H, s), 4.0 (6H, s), 3.5 (1H, d, J = (2H, d, J = 9Hz), 2.3 (2H, t, J = 9Hz)
1-92 NQ39 . 2-[2-(4- Amino - phenyl )- ethylamino ]-5,8- dimethoxy -[1,4]naphthoquinone 1-92 NQ39 . 2- [2- (4- Amino - phenyl ) - ethylamino] -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 2-(4-Amino phenyl) ethylamine (281.9 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:2) 에 의해 정제하여 생성물을 얻었다. Yield: 46.2% (225.1 mg)2- (4-Amino phenyl) ethylamine (281.9 μl, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL) The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 2) to give the product. Yield: 46.2% (225.1 mg)
1H-NMR (300Hz, CDCl3) δ 7.5 (1H, d, J=10.35Hz), 7.3 (1H, d, J=10.35Hz), 7.0 (2H, d, J=10.3Hz), 6.7 (2H, d, J=10.3Hz), 5.7 (1H, t), 5.6(1H, s), 4.0 (6H, s), 3.5 (2H, q, J=8Hz), 2.8 (2H, t, J=7.7Hz)
7.3 (1H, d, J = 10.35 Hz), 7.0 (2H, d, J = 10.3 Hz), 6.7 (2H, d, J = 10.35 Hz) (2H, t, J = 7.7 Hz), 5.7 (1H, s), 4.0 (6H, s)
1-93 NQ40 . 2-(2- Diethyamino - ethylamino )-5,8- dimethoxy -[1,4]naphthoquinone 1-93 NQ40. 2- (2- Diethyamino - ethylamino) -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 N,N- Diethy l ethylenedimine (293.32 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:4) 에 의해 정제하여 생성물을 얻었다. Yield: 63.9% (284.5 mg)N, N-Diethy l ethylenedimine (293.32 μl, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 4) to give the product. Yield: 63.9% (284.5 mg)
1H-NMR (300Hz, CDCl3) δ 7.9 (1H, d, J=10Hz), 7.1 (1H, d, J=10Hz), 6.6 (1H, s), 5.3 (1H, s), 4.0 (6H, s), 3.2 (4H, q, J=7Hz), 2.6 (4H, t, J=6.8Hz), 2.5 (6H, t, J=8Hz)
D, J = 10 Hz), 6.6 (1H, s), 5.3 (1H, s), 4.0 (6H, s) , 3.2 (4H, q, J = 7 Hz), 2.6 (4H, t, J = 6.8Hz), 2.5 (6H, t, J = 8Hz)
1-94 NQ41 . 5,8- Dimethoxy -2-(3- methyl - butylsulfanyl )-[1,4]naphthoquinone 1-94 NQ41 . 5,8- Dimethoxy -2- (3- methyl - butylsulfanyl ) - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 3-Methyl-1-butanethiol (256.8 μl, 1.65 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 상기 용액에 수(water) 중 sodium dichlromate (0.23 mmol) 및 sulphuric acid (0.76 mmol) 용액의 액적(dropwise)를 첨가하였다. 결과 반응물을 몇 분 동안 교반하고 산성 용액을 dichlromethane (50 mL ×3)으로 추출하였다. 결합된 유기층을 brine으로 세척하고, anhydrous sodium sulphate로 건조하고,여과한 후 감압 하 농축하였다. 잔류물을 칼럼 크로마토그래피(hexanes:EtOAc=5:1)에 의해 정제하여 생성물을 수득하였다. Yield: 71.5% (404.9 mg).
3-Methyl-1-butanethiol (256.8 μL, 1.65 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL) The reaction was stirred at room temperature for 4 hours and to this solution was added dropwise a solution of sodium dichlormate (0.23 mmol) and sulphuric acid (0.76 mmol) in water. The resulting reaction was stirred for several minutes and the acid solution was extracted with dichlromethane (50 mL x 3). The combined organic layers were washed with brine, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (hexanes: EtOAc = 5: 1) to give the product. Yield: 71.5% (404.9 mg).
*1H-NMR (300Hz, CDCl3) δ 7.5 (2H, d, J=10.3Hz), 4.0 (6H, s), 2.6 (2H, t, J=8Hz), 1.8 (1H, m), 1.5 (2H, m, J=7.3Hz), 1.0 (6H, d, J=7.4Hz)
(2H, t, J = 8 Hz), 1.8 (1H, m), 1.5 (2H, d, J = 10.3 Hz) , m, J = 7.3 Hz), 1.0 (6H, d, J = 7.4 Hz)
1-95 1-95 NQ42NQ42 . 2-. 2- ButylsulfanylButylsulfanyl -5,8--5,8- dimethoxydimethoxy -[1,4]- [1, 4] naphthoquinonenaphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 1,4-Diphenylene diamine (248.7 mg, 1.65 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 상기 용액에 수(water) 중 sodium dichlromate (0.23 mmol) 및 sulphuric acid (0.76 mmol) 용액의 액적(dropwise)을 첨가하였다. 혼합물을 몇 분 동안 교반하고 산성 용액을 dichlromethane (50 mL ×3)으로 추출하였다. 결합된 유기층을 brine으로 세척하고, anhydrous sodium sulphate로 건조하고, 여과한 후 감압 하 농축하였다. 잔류물을 칼럼 크로마토그래피(hexanes:EtOAc=5:1)에 의해 정제하여 생성물을 수득하였다. Yield: 67.9% (287.2 mg).1,4-Diphenylene diamine (248.7 mg, 1.65 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and a dropwise addition of sodium dichlormate (0.23 mmol) and sulphuric acid (0.76 mmol) in water was added to the solution. The mixture was stirred for several minutes and the acid solution was extracted with dichlromethane (50 mL x 3). The combined organic layers were washed with brine, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (hexanes: EtOAc = 5: 1) to give the product. Yield: 67.9% (287.2 mg).
1H-NMR (300Hz, CDCl3) δ 7.4 (2H, d, J=10.6Hz), 4.0 (6H,s), 2.7 (2H, t, J=7.3Hz), 1.7 (2H, m), 1.5 (2H, m), 1.0 (3H, t, J=8Hz)
(2H, m, J = 7.3 Hz), 1.7 (2H, m), 1.5 (2H, , m), 1.0 (3H, t, J = 8 Hz)
1-96 NQ43 . 4-(5,8- Dimethoxy -1,4- dioxo -1,4- dihydro - naphthalen -2-ylamino)-butyric acid 1-96 NQ43 . 4- (5,8- Dimethoxy- 1,4- dioxo- 1,4- dihydro - naphthalen -2- ylamino) -butyric acid
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 4-Aminobutyric Acid (213.45 mg, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc:MeOH=1:4:1) 에 의해 정제하여 생성물을 얻었다. Yield: 65.6% (289.1 mg).4-Aminobutyric acid (213.45 mg, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc: MeOH = 1: 4: 1) to give the product. Yield: 65.6% (289.1 mg).
1H-NMR (300Hz, DMSO) δ 7.5 (1H, d, J=10.5Hz), 7.4 (1H, d, J=10.5Hz), 7.0 (1H, t), 5.5 (1H, s), 4.0 (6H, s), 3.1 (2H, q, J=7.7Hz), 2.4 (2H, t, J=8Hz), 1.7 (2H, q, J=7.7Hz)
(1H, s), 4.0 (6H, s), 7.4 (1H, d, J = 10.5Hz) , s), 3.1 (2H, q, J = 7.7 Hz), 2.4 (2H, t, J = 8 Hz)
1-97 NQ44 . 2-(2,2- Dimethoxy - ethylamino )-5,8- dimethoxy -[1,4]naphthoquinone 1-97 NQ44 . 2- (2,2- Dimethoxy - ethylamino) -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 Amino acetaldehyde Dimethyl acetal (222.08 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:2) 에 의해 정제하여 생성물을 얻었다. Yield: 65.2% (370.7 mg).Amino acetaldehyde Dimethyl acetal (222.08 μL, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 2) to give the product. Yield: 65.2% (370.7 mg).
1H-NMR (300Hz, CDCl3) δ 7.4 (1H, d, J=10.3Hz), 7.3 (1H, d, J=10.3Hz), 5.9 (1H, s), 5.6 (1H, s), 4.6 (1H, t, J=9.3Hz), 4.0 (6H, s), 3.5 (6H, s), 3.3 (2H, t, J=6.8Hz)
(1H, s), 5.6 (1H, s), 4.6 (1H, d, J = 10.3Hz) (t, J = 9.3 Hz), 4.0 (6H, s), 3.5
1-98 NQ45 . 2-(2- Isopropoxy - ethylamino )-5,8- dimethoxy -[1,4]naphthoquinone 1-98 NQ45 . 2- (2- Isopropoxy - ethylamino) -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 2-Aminoethyl Isopropyl Ether (213.5 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:2) 에 의해 정제하여 생성물을 얻었다. Yield: 37% (244.8 mg).2-Aminoethyl Isopropyl Ether (213.5 μL, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 2) to give the product. Yield: 37% (244.8 mg).
1H-NMR (300Hz, CDCl3) δ 7.5 (1H, d, J=10.3Hz), 7.3 (1H, d, J=10.3Hz), 6.1 (1H, m), 5.6 (1H, s), 4.0 (6H, s), 3.6 (2H, t, J=7Hz), 3.5 (1H, m), 3.3 (2H, q, J=6.8Hz), 1.6 (6H, d, J=7Hz)
(1H, s), 4.0 (6H, d, J = 10.3Hz), 7.3 (2H, q, J = 6.8 Hz), 1.6 (6H, d, J = 7 Hz)
1-99 NQ46 . 2-(3- Diethylamino - propylamino )-5,8- dimethoxy -[1,4]naphthoquinone 1-99 NQ46 . 2- (3- Diethylamino - propylamino) -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 N,N-Diethyl-1,3-diaminoethylene (328.75 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc:MeOH=1:3:1) 에 의해 정제하여 생성물을 얻었다. Yield: 58.58% (420 mg)N, N-Diethyl-1,3-diaminoethylene (328.75 μl, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc: MeOH = 1: 3: 1) to give the product. Yield: 58.58% (420 mg)
1H-NMR (300Hz, CDCl3) δ 7.4 (1H, d, J=10.6Hz), 7.3 (1H, d, J=10.3Hz), 6.8 (1H, s), 5.6 (1H, s), 4.0 (6H, s), 3.3 (2H, q, J=6.8Hz), 2.5 (6H, m), 1.8(2H, q, J=7.3Hz), 1.0 (6H, t, J=7.7Hz)
(1H, s), 4.0 (6H, s), 7.3 (1H, d, J = 10.3Hz) q, J = 7.3 Hz), 1.0 (6H, t, J = 7.7 Hz), 2.5 (6H, m)
1-100 NQ47 . 2-(2- Dimethylamino - ethylamino )-5,8- dimethoxy -[1,4]naphthoquinone 1-100 NQ47 . 2- (2- Dimethylamino - ethylamino) -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 N,N-Dimethylethylenediamine 225.27 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc:MeOH=1:3:1) 에 의해 정제하여 생성물을 얻었다. Yield: 56.76% (357.6 mg)N, N-Dimethylethylenediamine (225.27 μl, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc: MeOH = 1: 3: 1) to give the product. Yield: 56.76% (357.6 mg)
1H-NMR (300Hz, CDCl3) δ 7.4 (1H, d, J=10.6Hz), 7.2 (1H, d, J=10.6Hz), 6.3 (1H, s), 5.6 (1H, s), 4.0 (6H, s), 3.2 (2H, q, J=9.3Hz), 2.5 (2H, t, J=6.8Hz), 2.3 (6H, s)
6.6 (1H, s), 4.0 (6H, s), 7.2 (1H, d, J = 10.6Hz) (2H, t, J = 6.8Hz), 2.3 (6H, s), 3.2
1-101 NQ48 . 2-(2- Hydroxy - propylsulfanyl )-5,8- dimethoxy -[1,4]naphthoquinone 1-101 NQ48 . 2- (2- Hydroxy - propylsulfanyl) -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 1-Mercapto-2-propanol (190.77 μl, 1.65 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 상기 용액에 수(water) 중 sodium dichlromate (0.23 mmol) 및 sulphuric acid (0.76 mmol) 용액의 액적(dropwise)을 첨가하였다. 혼합물을 몇 분 동안 교반하고 산성 용액을 dichlromethane (50 mL ×3)으로 추출하였다. 결합된 유기층을 brine으로 세척하고, anhydrous sodium sulphate로 건조하고, 여과한 후 감압 하 농축하였다. 잔류물을 칼럼 크로마토그래피(hexanes:EtOAc=1:4)에 의해 정제하여 생성물을 수득하였다. Yield: 75% (319.2 mg)1-Mercapto-2-propanol (190.77 [mu] l, 1.65 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and a dropwise addition of sodium dichlormate (0.23 mmol) and sulphuric acid (0.76 mmol) in water was added to the solution. The mixture was stirred for several minutes and the acid solution was extracted with dichlromethane (50 mL x 3). The combined organic layers were washed with brine, dried over anhydrous sodium sulphate, filtered and concentrated under reduced pressure. The residue was purified by column chromatography (hexanes: EtOAc = 1: 4) to give the product. Yield: 75% (319.2 mg)
1H-NMR (300Hz, DMSO) δ 7.5 (2H, d, J=9.3Hz), 6.5 (1H, s), 5.1 (2H, d, J=6.3), 3.85 (6H, s), 2.8 (1H, m), 1.2 (3H, d, J=6.7Hz)
(2H, d, J = 6.3), 3.85 (6H, s), 2.8 (1H, d, J = m), 1.2 (3H, d, J = 6.7 Hz)
1-102 NQ49 . 2-(3- Dimethylamino - propylamino )-5,8- dimethoxy -[1,4]naphthoquinone 1-102 NQ49 . 2- (3- Dimethylamino - propylamino) -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 N,N- Dimethylpropane diamine (515.8 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc:MeOH=1:3:1) 에 의해 정제하여 생성물을 얻었다. Yield: 64.6% (284.1 mg)N, N-Dimethylpropane diamine (515.8 μL, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc: MeOH = 1: 3: 1) to give the product. Yield: 64.6% (284.1 mg)
1H-NMR (300Hz, CDCl3) δ 7.4 (1H, d, J=10Hz), 7.3 (1H, d, J=10Hz), 6.6 (1H, s), 5.6 (1H, s), 4.0 (6H, s), 3.2 (2H, q, J=8Hz), 2.45 (2H, q, J=7Hz), 2.3 (6H, s), 1.7 (2H, q, J=7Hz)
6.6 (1H, s), 4.0 (6H, s), 7.3 (1H, d, J = 10 Hz) ), 3.2 (2H, q, J = 8 Hz), 2.45 (2H, q, J = 7 Hz), 2.3 (6H, s)
1-103 NQ50 . 5,8- Dimethoxy -2-(2- methylamino - ethylamino )-[1,4]naphthoquinone 1-103 NQ50 . 5,8- Dimethoxy -2- (2- methylamino - ethylamino ) - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 N-Ethyl ethylene diamine (217.2 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc:MeOH=1:4:1) 에 의해 정제하여 생성물을 얻었다. Yield: 54.2% (228 mg).N-Ethyl ethylene diamine (217.2 μL, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc: MeOH = 1: 4: 1) to give the product. Yield: 54.2% (228 mg).
1H-NMR (300Hz, DMSO) δ 7.5 (1H, d, J=10Hz), 7.4 (1H, d, J=10Hz), 7.0 (1H, t, J=6.8Hz), 5.5 (1H, s), 3.8 (6H, s), 3.6 (2H, q, J=7.3Hz), 2.3 (4H, t, J=6.0Hz), 1.7 (3H, t, J=7.7Hz)
D, J = 10 Hz), 7.0 (1H, t, J = 6.8 Hz), 5.5 (1H, s), 7.4 2.3 (4H, t, J = 6.0 Hz), 1.7 (3H, t, J = 7.7 Hz), 3.8 (6H, s)
1-104 NQ51. 12-(5,8- Dimethoxy -1,4- dioxo -1,4- dihydro - naphthalen -2-ylamino)dodecanoic acid 1-104 NQ51 . 12- (5,8- Dimethoxy- 1,4- dioxo- 1,4- dihydro - naphthalen -2- ylamino) dodecanoic acid
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 12-Aminolauric acid (445.7 mg, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 MeOH에 의해 재결정화하여 생성물을 얻었다. Yield: 45.2% (269 mg)12-Aminolauric acid (445.7 mg, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL) The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was recrystallized by MeOH to give the product. Yield: 45.2% (269 mg)
1H-NMR (300Hz, DMSO) δ 7.5 (1H, d, J=10.7Hz), 7.4 (1H, d, J=10.7Hz), 7.0 (1H, t, J=6.8Hz), 5.4 (1H, s), 3.8 (6H, s), 3.0 (2H, q, J=7.3Hz), 2.2 (2H, q, J=8.3Hz), 1.3 (18H, m)
(1H, d, J = 10.7 Hz), 7.0 (1H, t, J = 6.8 Hz), 5.4 Q, J = 8.3 Hz), 1.3 (18H, m), 3.8 (6H, s), 3.0
1-105 1-105 NQ52NQ52 . 2-(2-. 2- (2- HydroxyHydroxy -- ethylaminoethylamino )-5,8-) -5,8- dimethoxydimethoxy -[1,4]- [1, 4] naphthoquinonenaphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 Ethanol amine Hydrochloride (201.9 mg, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc=1:4)에 의해 정제하여 생성물을 얻었다. Yield: 94.2% (362.8 mg)Ethanol amine hydrochloride (201.9 mg, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc = 1: 4) to give the product. Yield: 94.2% (362.8 mg)
1H-NMR (300Hz, DMSO) δ 7.5 (1H, d, J=11Hz), 7.4 (1H, d, J=11Hz), 6.0 (1H, t, J=6.8Hz), 5.5 (1H, s), 3.8 (6H, s), 3.1 (2H, t, J=9.3Hz)
D, J = 11 Hz), 6.0 (1H, t, J = 6.8 Hz), 5.5 (1H, s), 7.4 3.8 (6H, s), 3.1 (2H, t, J = 9.3 Hz)
1-106 NQ53 . 2-[2-(2- Hydroxy - ethoxy )- ethylamino ]-5,8- dimethoxy -[1,4]naphthoquinone 1-106 NQ53 . 2- [2- (2- Hydroxy - ethoxy ) - ethylamino] -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 2-(2-Aminoethoxy) ethanol (217 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피 (hexanes:EtOAc:MeOH=1:4:1)에 의해 정제하여 생성물을 얻었다. Yield: 67.2% (297.8 mg)2- (2-Aminoethoxy) ethanol (217 μl, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOAc: MeOH = 1: 4: 1) to give the product. Yield: 67.2% (297.8 mg)
1H-NMR (300Hz, CDCl3)δ7.45(1H,d,J=10.3Hz),7.4(1H,d,J=10.3Hz),6.0(1H,t,J=7.7Hz),5.6(1H,s),4.0(6H,s),3.7(2H,t,J=8.3Hz),3.5(2H,t,J=8.3Hz),2.8(2H,q,J=6.3Hz).
D, J = 10.3 Hz), 6.0 (1H, t, J = 7.7 Hz), 5.6 (1H, s), 4.0 (6H, s), 3.7 (2H, t, J = 8.3Hz), 3.5 (2H, t, J = 8.3Hz), 2.8 (2H, q, J = 6.3Hz).
1-107 NQ54 . 2-(3- Dibutylamino - propylamino )-5,8- dimethoxy -[1,4]naphthoquinone 1-107 NQ54 . 2- (3- Dibutylamino - propylamino) -5,8- dimethoxy - [1,4] naphthoquinone
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 3-(Dibutylamino)propylamine (385.7 μl, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 칼럼 크로마토그래피(hexanes:EtOA=1:2)에 의해 정제하여 생성물을 얻었다. Yield: 66.2% (367.8 mg)3- (Dibutylamino) propylamine (385.7 μL, 2.07 mmol) was added to a solution of 5,8-dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was purified by column chromatography (hexanes: EtOA = 1: 2) to give the product. Yield: 66.2% (367.8 mg)
1H-NMR (300Hz, CDCl3) δ 7.4 (1H, d, J=10.7Hz), 7.3 (1H, d, J=10.7Hz), 6.6 (1H, s), 5.6 (1H, s), 3.9 (6H, s), 3.3 (2H, q, J=6.3Hz), 2.5 (2H, t, J=7.0Hz), 2.4 (4H, t, J=7.3Hz), 1.5 (2H, q, J=8.0Hz), 1.4 (4H, t, J=6Hz), 1.3 (4H, t, J=8.0Hz), 1.0 (6H, t, J=8.0Hz)
(1H, s), 3.9 (6H, d, J = 10.7 Hz), 7.3 (1H, , s), 3.3 (2H, q, J = 6.3 Hz), 2.5 (2H, t, J = 7.0 Hz), 2.4 , 1.4 (4H, t, J = 6 Hz), 1.3 (4H, t, J = 8.0 Hz), 1.0 (6H,
1-108 NQ55 . 6-(5,8- Dimethoxy -1,4- dioxo -1,4- dihydro - naphthalen -2-ylamino)-hexanoic acid 1-108 NQ55. 6- (5,8- Dimethoxy- 1,4- dioxo- 1,4- dihydro - naphthalen -2- ylamino) -hexanoic acid
MeOH (30 mL) 중 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) 용액에 6-Aminohexanoic Acid (271.52 mg, 2.07 mmol)을 첨가하였다. 반응물을 상온에서 4시간 동안 교반하고 감압 하 증발시켰다. 조 생성물을 MeOH에 의해 재결정화하여 생성물을 얻었다. Yield: 44.2% (212 mg)6-Aminohexanoic Acid (271.52 mg, 2.07 mmol) was added to a solution of 5,8-Dimethoxynaphthalene-1,4-dione (301 mg, 1.38 mmol) in MeOH (30 mL). The reaction was stirred at room temperature for 4 hours and evaporated under reduced pressure. The crude product was recrystallized by MeOH to give the product. Yield: 44.2% (212 mg)
1H-NMR (300Hz, DMSO) δ 7.5 (1H, d, J=10Hz), 7.4 (1H, d, J=10Hz), 7.0 (1H, t, J=7.0Hz), 5.4 (1H, s), 4.0 (6H, s), 3.0 (2H, t, J=7.7Hz), 2.2 (2H, t, J=7.7Hz), 1.5 (4H, q, J=8.7Hz), 1.3 (2H, q, J=7.3Hz).
D, J = 10 Hz), 7.0 (1H, t, J = 7.0 Hz), 5.4 (1H, s), 7.4 Q, J = 8.7 Hz), 1.3 (2H, q, J = 7.7 Hz), 3.0 (2H, t, J = = 7.3 Hz).
1-109 NQ38 -p. 1- Benzyl -4-(5,8- dimethoxy -1,4- dioxo -1,4- dihydro -naphthalen-2-ylamino)-1-methyl-piperidinium 1-109 NQ38 -p. 1- Benzyl -4- (5,8- dimethoxy- 1,4- dioxo- 1,4- dihydro - naphthalen-2-ylamino) -1-methyl-piperidinium
DMF (5 mL) 중 NQ38 (65 mg, 0.16 mmol)의 100 mL 플라스크 용액에 Iodomethane (24.3 μl, 0.16 mmol)을 첨가하였다. 반응 혼합물을 상온에서 48시간 동안 교반하였다. 플라스크에 물을 첨가하고, 반응물을 여과하고 농축하였다. 조 생성물을 acetic acid 및 ethyl acetate에 의해 정제하였다. Yield: 37% (25 mg)Iodomethane (24.3 μL, 0.16 mmol) was added to a 100 mL flask solution of NQ38 (65 mg, 0.16 mmol) in DMF (5 mL). The reaction mixture was stirred at room temperature for 48 hours. Water was added to the flask, and the reaction was filtered and concentrated. The crude product was purified by acetic acid and ethyl acetate. Yield: 37% (25 mg)
1H-NMR (300Hz, D2O) δ 7.5 (1H, d, J=10.7Hz), 6.8 (1H, d, J=10.7Hz), 5.6 (1H, s), 4.5 (2H, s), 3.8 (6H, s), 3.0 (3H, s), 2(2H, m)
(1H, s), 4.5 (2H, s), 3.8 (6H, d, J = 10.7Hz) , s), 3.0 (3H, s), 2 (2H, m)
1-110 NQ40 -p. [2-(5,8- Dimethoxy -1,4- dioxo -1,4- dihydro - naphthalen -2-ylamino)-ethyl]-diethyl-methyl-ammonium 1-110 NQ40 -p. [2- (5,8- Dimethoxy- 1,4- dioxo- 1,4- dihydro - naphthalen -2- ylamino) -ethyl] -diethyl-methyl-ammonium
DMF (5 mL) 중 NQ40 (51.5 mg, 0.16 mmol)의 100 mL 플라스크 용액에 Iodomethane (24.3 μl, 0.16 mmol)을 첨가하였다. 반응 혼합물을 상온에서 48시간 동안 교반하였다. 플라스크에 물을 첨가하고, 반응물을 여과하고 농축하였다. 조 생성물을 acetic acid 및 ethyl acetate에 의해 정제하였다. Yield: 37.7% (21 mg).Iodomethane (24.3 μl, 0.16 mmol) was added to a 100 mL flask solution of NQ40 (51.5 mg, 0.16 mmol) in DMF (5 mL). The reaction mixture was stirred at room temperature for 48 hours. Water was added to the flask, and the reaction was filtered and concentrated. The crude product was purified by acetic acid and ethyl acetate. Yield: 37.7% (21 mg).
1H-NMR (300Hz, D2O) δ 7.5 (1H, d, J=10.6Hz), 7.45 (1H, d, J=10.6Hz), 5.3 (1H, s), 3.8 (6H, s), 3.5 (2H, q, J=6Hz), 3.0 (3H, s), 2.5 (4H, t, J=6.3Hz), 1.3 (6H, t, J=8Hz)
(1H, d, J = 10.6 Hz), 5.3 (1H, s), 3.8 (6H, s), 3.5 , q, J = 6 Hz), 3.0 (3H, s), 2.5 (4H, t, J =
1-111 NQ46 -p. [3-(5,8- Dimethoxy -1,4- dioxo -1,4- dihydro - naphthalen -2-ylamino)-popyl]-diethyl-methyl-ammonium 1-111 NQ46 -p. [3- (5,8- Dimethoxy- 1,4- dioxo- 1,4- dihydro - naphthalen -2- ylamino) -polyl] -diethyl-methyl-ammonium
DMF (5 mL) 중 NQ46 (55.4 mg, 0.16 mmol)의 100 mL 플라스크 용액에 Iodomethane (24.3 μl, 0.16 mmol)을 첨가하였다. 반응 혼합물을 상온에서 48시간 동안 교반하였다. 플라스크에 물을 첨가하고, 반응물을 여과하고 농축하였다. 조 생성물을 acetic acid 및 ethyl acetate에 의해 정제하였다. Yield: 25.4% (14.7 mg).Iodomethane (24.3 μl, 0.16 mmol) was added to a 100 mL flask solution of NQ46 (55.4 mg, 0.16 mmol) in DMF (5 mL). The reaction mixture was stirred at room temperature for 48 hours. Water was added to the flask, and the reaction was filtered and concentrated. The crude product was purified by acetic acid and ethyl acetate. Yield: 25.4% (14.7 mg).
1H-NMR (300Hz, D2O) δ 7.4 (1H, d, J=10.3Hz), 7.25 (1H, d, J=10.3Hz) 5.4(1H, s), 3.6 (6H, s), 3.3 (6H, q, J=7.3Hz), 2.8 (3H, s), 2.6 (4H, s), 1.2 (6H, t, J=8.3Hz)
(1H, s), 3.6 (6H, s), 3.3 (6H, d, J = 10.3Hz) q, J = 7.3 Hz), 2.8 (3H, s), 2.6 (4H, s), 1.2 (6H, t,
1-112 NQ47 -p. [2-(5,8- Dimethoxy -1,4- dioxo -1,4- dihydro - naphthalen -2-ylamion)-ethyl]-trimethyl-ammonium 1-112 NQ47 -p. [2- (5,8- Dimethoxy- 1,4- dioxo- 1,4- dihydro - naphthalen -2- ylamion) -ethyl] -trimethyl-ammonium
DMF (5 mL) 중 NQ47 (48.7 mg, 0.16 mmol)의 100 mL 플라스크 용액에 Iodomethane (24.3 μl, 0.16 mmol)을 첨가하였다. 반응 혼합물을 상온에서 48시간 동안 교반하였다. 플라스크에 물을 첨가하고, 반응물을 여과하고 농축하였다. 조 생성물을 acetic acid 및 ethyl acetate에 의해 정제하였다. Yield: 58.7% (30 mg)Iodomethane (24.3 μl, 0.16 mmol) was added to a 100 mL flask solution of NQ47 (48.7 mg, 0.16 mmol) in DMF (5 mL). The reaction mixture was stirred at room temperature for 48 hours. Water was added to the flask, and the reaction was filtered and concentrated. The crude product was purified by acetic acid and ethyl acetate. Yield: 58.7% (30 mg)
1H-NMR (300Hz, D2O) δ 7.4 (1H, d, J=10.3Hz), 7.3 (1H, d, J=10.3Hz), 5.4 (1H, s), 3.7 (6H, s), 3.6 (2H, t, J=7Hz), 3.5 (2H, t, J=6.8Hz), 3.1 (9H, s)
(1H, s), 3.7 (6H, s), 3.6 (2H, s), 7.4 (1H, d, J = 10.3Hz) , t, J = 7 Hz), 3.5 (2H, t, J = 6.8 Hz), 3.1 (9H, s)
1-113 NQ49 -p. [3-(5,8- Dimethoxy -1,4- dioxo -1,4- dihydro - naphthalen -2-ylamino)-propyl]-trimethyl-ammonium 1-113 NQ49 -p. [3- (5,8- Dimethoxy- 1,4- dioxo- 1,4- dihydro - naphthalen -2- ylamino) -propyl] -trimethyl-ammonium
DMF (5 mL) 중 NQ49 (50.9 mg, 0.16 mmol)의 100 mL 플라스크 용액에 Iodomethane (24.3 μl, 0.16 mmol)을 첨가하였다. 반응 혼합물을 상온에서 48시간 동안 교반하였다. 플라스크에 물을 첨가하고, 반응물을 여과하고 농축하였다. 조 생성물을 acetic acid 및 ethyl acetate에 의해 정제하였다. Yield: 34.8% (18.6 mg)Iodomethane (24.3 μl, 0.16 mmol) was added to a 100 mL flask solution of NQ49 (50.9 mg, 0.16 mmol) in DMF (5 mL). The reaction mixture was stirred at room temperature for 48 hours. Water was added to the flask, and the reaction was filtered and concentrated. The crude product was purified by acetic acid and ethyl acetate. Yield: 34.8% (18.6 mg)
1H-NMR (300Hz, D2O) δ 7.3 (1H, d, J=11Hz), 7.1 (1H, s, J=11Hz), 5.3 (1H, s), 3.6 (6H, s), 3.4 (2H, t, J=8Hz), 3.3 (2H, t, J=8Hz), 2.5 (9H, s), 2.0 (2H, m)
(1H, s), 7.3 (1H, s), 3.4 (2H, t), 7.3 (1H, d, J = (2H, m, J = 8 Hz), 3.3 (2H, t, J = 8 Hz)
실시예Example 2 : 유해조류 2: harmful algae 살조Shame 효과 effect
본 발명에 따른 화합물들의 다양한 접종농도에서의 유해조류 살조 효과를 측정하였다.The effects of the compounds according to the invention on the algae killing effect at various inoculation concentrations were determined.
본 발명자들은 실시예 1에서 제조된 화합물 중 나프토퀴논 115개의 화합물에 대해서 각 농도별로 유해조류에 대한 살조 효과를 조사하였다. The present inventors investigated the killing effect of naphthoquinone compounds on the harmful algae at each concentration for the compounds of Example 1.
이를 위해 처리구(실험군)로서 유해조류로는 남조류인 마이크로시스티스 아에루기노사, 아나베나 플로스-아쿠아, 규조류인 스테파노디스커스 한츠치, 사이클로텔라 메네기니아, 녹조류인 시네데스무스 액투스, 와편모조류인 페리디니움 바이패스를 사용하였고, 대조구로는 무해조류인 규조류 아울라코 세이라를 사용하였다. 배양조건은 하기의 [표 4]와 같다.(표4 - 주요 녹조유발 조류의 배양 배지 및 배양 조건)For this purpose, as the experimental group, harmful algae include microcystis aeruginosa, anabenaflus-aqua, which is a cyanobacterium, anatomica diatomaceae such as Stephanos discus, Cyclotella menegnia, Peridinium bypass was used as a parent algae, and seaweed aleucocera, an anhydrous algae, was used as a control. The culture conditions are shown in Table 4 below. (Table 4 - Culture Medium and Culture Conditions of Main Algae-Induced Algae)
(표 4)(Table 4)
실험은 우선 각각 10 mL의 마이크로시스티스 아에루기노사, 아나베나 플로스-아쿠아, 스테파노디스커스 한츠치, 시네데스무스 액투스, 아울라코 세이라 등을 5 × 105 cells/ mL이 되도록 준비하였으며, 사이클로텔라 메네기니아의 경우에는 1 × 105 cells/ mL, 페리디니움 바이패스의 경우에는 1 × 103 cells/ mL로 준비한 후 실시예 1에 명기된 화합물을 다양한 농도로 접종하여 최종농도가 각각 0.1, 0.2, 0.5, 1, 2, 5, 10, 20, 50 μM이 되도록 처리해 주었다. In the experiment, 10 mL of each of microsysteas aeruginosa, anabenaflus-aqua, strepanodiscus tsuchi, Cine desmus acutus, and auracocera were prepared to give a concentration of 5 × 10 5 cells / mL , 1 × 10 5 cells / mL for cycloterrorenegnia, 1 × 10 3 cells / mL for peridinium bypass, and then inoculated at various concentrations to the compound described in Example 1 to give a final concentration , 0.1, 0.2, 0.5, 1, 2, 5, 10, 20, and 50 μM, respectively.
처리조건은 접종 후 조류의 배양조건 하에서 10일 동안 배양하면서, 정립 또는 도립 현미경 하에서 SR-chamber 또는 heamocytometer를 통해 육안으로 직접 계수해 주었다. 이후 처리 10일 후, 세포의 감소율(reduction ratio), 즉 살조 활성(%)을 하기 식을 사용해 계산하였다.The treatment conditions were directly visual counted by SR-chamber or heamocytometer under an in-situ or inverted microscope, while culturing for 10 days under culture conditions of algae after inoculation. 10 days after the treatment, the reduction ratio of the cells, i.e., the killing activity (%), was calculated using the following equation.
살조 활성(%)=(1-Tt/Ct) x 100Tear activating activity (%) = (1-Tt / Ct) x 100
상기 식에서, T는 화합물 처리후 세포의 밀도를 나타낸 것이고, C는 화합물을 처리하지 않은 세포의 밀도를 나타낸 것이며, t는 배양 시간을 나타낸 것이다.T represents the density of cells after compound treatment, C represents the density of cells not treated with the compound, and t represents the incubation time.
상기 식을 바탕으로 구한 각 화합물의 접종농도별 살조 활성을 바탕으로 IC50을 구하기 위해 standard curve인 four Parameter logistic curve (J.W.A. Findlay and R.F. Dillard, 2007,The AAPS Journal, E260-E267)을 사용하였다.A four parameter logistic curve (JWA Findlay and RF Dillard, 2007, The AAPS Journal, E260-E267) was used to calculate the IC 50 based on the killing activity of each compound in the inoculum concentration.
Y는 화합물 각각의 접종농도에 따른 살조활성(%)을 나타내며, A는 접종농도에 따른 최대 살조활성(%), D는 접종농도에 따른 최소 살조활성(%), C는 접종농도 범위 내의 IC50값, B는 - Hillslope (- 기울기) 값을 의미한다. 따라서 상기 식을 사용해 접종농도 별 살조 활성의 IC50값을 구하여 그 결과를 하기의 [표 5]에 나타내었다.(표 5 - 유해조류에 대한 살조 효과)Y is the maximum killing activity (%) according to the inoculation concentration, A is the minimum killing activity (%) according to the inoculation concentration, C is the IC50 Value, and B - means Hillslope (- slope) value. Therefore, the IC 50 value of the killing activity by the inoculum concentration was determined using the above equation, and the results are shown in Table 5 below. (Table 5 - Salivation effect on harmful birds)
(표 5)(Table 5)
그 결과, [표 5]에서 보는 바와 같이, 본 발명의 화합물들은 남조류인 마이크로시스티스 아에루기노사에 대해 낮은 농도에서도 우수한 살조 효과가 있는 것을 확인할 수 있었으며, 특히 01-4, 01-3, 03-3, 04-4, 05-4, 05-3, 06-3, 07-4, 09-4, 09-3, 15-4, 18-4, 40, 42, 46, 48, 49, 54, 38-p, 46-p 등은 1 μM 이하의 미량의 농도에서 IC50값을 보여 우수한 살조 효과를 확인하였다. 특히, 화합물 48, 6-3 및 40 등은 IC50값이 각각 130 nM, 160 nM 및 160 nM 인 것으로 확인되어 가장 우수한 살조효과를 보유하고 있었다.As a result, as shown in [Table 5], it was confirmed that the compounds of the present invention had an excellent killing effect against microcystis aeruginosa, which is a cyanobacteria, even at a low concentration, especially 01-4, 01-3, 03-4, 05-4, 05-3, 06-3, 07-4, 09-4, 09-3, 15-4, 18-4, 40, 42, 46, 48, 49, 54, 38-p, and 46-p showed IC 50 values at a trace concentration of 1 μM or less. In particular, compounds 48, 6-3 and 40 and the like were found to have IC 50 values of 130 nM, 160 nM and 160 nM, respectively, and thus had the best killing effect.
아나배나 플로스-아쿠아의 경우에는 01-4, 01-3, 02-3, 03-4, 04-4, 05-4, 07-4, 07-3, 09-4, 09-3, 10-3, 11-4, 11-3, 13-3, 15-4, 15-3, 18-4, 19-4, 19-3, 22-4, 26, 27, 32, 35, 38, 40, 44, 45, 46, 47, 48, 52, 53, 40-p, 46-p, 47-p 등이 1 μM 이하 농도에서 IC50값을 보여 살조활성이 우수하였으며, 그 중 15-3(170 nM), 47(170nM), 40(190 nM)의 순으로 가장 우수한 살조효과를 확인하였다.In the case of Anaabana Flos-Aqua, you can choose from 01-4, 01-3, 02-3, 03-4, 04-4, 05-4, 07-4, 07-3, 09-4, 09-3, 10 -3, 11-4, 11-3, 13-3, 15-4, 15-3, 18-4, 19-4, 19-3, 22-4, 26, 27, 32, 35, 38, 40 , 44, 45, 46, 47, 48, 52, 53, 40-p, 46-p and 47-p showed IC 50 values at concentrations below 1 μM, 170 nM), 47 (170 nM) and 40 (190 nM), respectively.
규조류인 스테파노디스커스 한츠치에서는 01-4, 01-3, 02-4, 02-3, 03-4, 03-3, 04-4, 05-4, 05-3, 09-4, 09-3, 10-3, 15-4, 15-3, 16-4, 18-4, 22-4, 41, 42, 44 등의 살조활성이 우수하였으며, 그 중 22-4(40 nM), 4-4(170 nM)와 18-4(170 nM)의 순으로 가장 우수한 살조효과를 확인하였다.Stefano Duskus, a diatomite, is the best player in the world. , 10-4, 15-4, 15-3, 16-4, 18-4, 22-4, 41, 42 and 44. Among them, 22-4 (40 nM), 4- 4 (170 nM) and 18-4 (170 nM), respectively.
사이클로텔라 메네기니아의 경우에는 04-3, 15-3 등의 살조활성이 우수하였으며, 그 중 04-3(170 nM)이 가장 우수한 살조효과를 확인하였다. 상기조류는 상대적으로 다른 조류에 비해 적은 수의 화합물만이 살조효과가 우수한 것으로 조사되었다.In the case of Cyclotella menegnia, 04-3 and 15-3 were excellent in killing activity, and 04-3 (170 nM) showed the best killing effect. Only a small number of compounds of the algae were found to be superior to other algae.
규조 아울라코세이라 그라뉴라타의 경우에는 대부분의 화합물이 효과가 없었으나 19-3에서 900 nM의 IC50값을 확인할 수 있었다.In the case of diatom Aureococci gracilurata, most of the compounds were ineffective, but IC50 values of 19-3 to 900 nM were obtained.
와편모조 패리디니움 바이패스의 경우에는 06-3, 07-3, 20-3, 22-4, 22-3, 25, 26, 27, 28 등의 살조활성이 우수하였으며, 22-4(0.75 nM), 28(0.86 nM) 순으로 가장 우수한 살조효과를 확인하였다.
In the case of phloem mimetic paradinium bypass, the killing activity of 06-3, 07-3, 20-3, 22-4, 22-3, 25, 26, 27, nM) and 28 (0.86 nM), respectively.
따라서 상기 결과를 통해 본 발명자들은 본 발명의 화합물을 유효성분으로 포함하는 조성물이 아울라코세이라 그라뉴라타, 시네데스무스 액투스와 같이 담수와 기수역에서 녹조를 일으키지 않는, 즉, 문제가 되지 않는 종들에게는 거의 영향을 미치지 않는 반면, 국내외에서 녹조현상을 유발시켜 큰 문제를 발생시키는 담수산 유해조류에 대하여 우수한 살조효과가 있음을 알 수 있었다.
Therefore, the inventors of the present invention have found that the composition containing the compound of the present invention as an active ingredient does not cause algae in fresh water and in the marine waters, that is, does not cause any problem, such as Aureococeira lanurata and Cine desmus acatus While it has little effect on the species, it is found that there is an excellent killing effect on the harmful algae of freshwater fish causing great problems by causing algae phenomenon at home and abroad.
실시예Example 3 : 녹조의 종류와 녹조발생단계에 따른 신규 화합물의 선택과 접종량 결정 3: Selection of new compounds and determination of inoculation amount according to the kind of green tide and the stage of green tide generation
실시예 2에서 우수한 살조활성을 보유한 신규 화합물을 대상으로 조류주의보, 경보, 대발생 수준의 녹조 발생 시 효과적으로 대처할 수 있는 적정농도를 찾고자 하였다.A novel compound having an excellent killing activity in Example 2 was searched to find an appropriate concentration to cope with algae warning, warning, and occurrence of algae at an occurrence level.
우선 Microcystis aeruginosa, Anabaena flos-aquae, Stephanodiscus hantzschii, Peridinium bipes 등을 조류초기단계(1 × 103 cells/ml, 페리디니움의 경우 3 × 102 cells/ml), 조류발전단계(1 × 105 cells/ml, 페리디니움의 경우 1 × 103 cells/ml), 조류대발생(1 × 106 cells/ml, 페리디니움의 경우 5 × 103 cells/ml) 수준으로 준비하였다.(1 × 10 3 cells / ml for peridinium, 3 × 10 2 cells / ml for peridinium), algae development stage (1 × 10 5 cells / ml), and microbial flora of Anabena flos-aquae, Stephanodiscus hantzschii and peridinium bipes cells / ml, were prepared in a 1 × 10 3 cells / ml) , for generating a bird (1 × 10 6 cells / ml , ferry D 5 × 10 3 cells / ml) levels for nium for ferry di nium.
마이크로시스티스 아에루기노사에 선택적인 제어가 가능한 신규 화합물 48, 6-3 및 40 등의 접종농도가 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2 μM이 되도록 해당조류의 조류초기, 조류발전, 조류대발생단계에 각각 접종해 주었다.0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, and 2 μM of the new compounds 48, 6-3 and 40 and the like which can be selectively controlled on the microsystease eruginosa They were inoculated at the early stage, the tidal stage, and the tidal stage of the corresponding tidal flats, respectively.
다음으로 아나배나 플로스-아쿠아에 선택적인 제어가 가능한 신규 화합물 15-3, 47 및 40 등의 접종농도가 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2 μM이 되도록 해당조류의 조류초기, 조류발전, 조류대발생단계에 각각 접종해 주었다.Next, the inoculum concentrations of the new compounds 15-3, 47 and 40, which can be selectively controlled in anabaena flos-aqua, are 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, , And inoculated at the early stage, algae stage, and bird stage stage of the corresponding algae, respectively.
또한 스테파노디스커스 한츠치에 선택적인 제어가 가능한 신규 화합물 22-4, 4-4, 4-3 및 18-4 등의 접종농도가 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2 μM이 되도록 해당조류의 조류초기, 조류발전, 조류대발생단계에 각각 접종해 주었다. In addition, the inoculation concentrations of the novel compounds 22-4, 4-4, 4-3 and 18-4, which are selectively controllable in Stefano discus tsutsugi, are 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9 , 1, and 2 μM, respectively, at the beginning of the tidal flow, the tidal flow, and the tidal flow stage.
마지막으로 페리디니움 바이패스에 선택적인 제어가 가능한 신규 화합물 22-4, 28 등의 접종농도가 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1, 2 μM이 되도록 해당조류의 조류초기, 조류발전, 조류대발생단계에 각각 접종해 주었다.
Finally, the inoculation concentrations of new compounds 22-4, 28, etc., which can be selectively controlled on peridinium bypass, are 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, They were inoculated at the beginning of the bird, at the development of the bird, and at the development stage of the bird.
실험결과를 도 2에 나타내었다.The experimental results are shown in Fig.
도 2와 같이, 신규 화합물 48, 6-3, 15-3, 47 및 40 등은 남조류인 마이크로시스티스 아에루기노사 또는 아나배나 플로스-아쿠아 등이 조류초기, 조류발전, 조류대발생 단계로 존재할 때 접종하여 최종농도가 각각 0.2, 0.5, 1 μM이 되면, 해당수계 내 남조류의 90% 이상을 효과적으로 제어가능하였다.As shown in Fig. 2, the new compounds 48, 6-3, 15-3, 47, and 40 and the like are microcystis aeruginosa or anabonaflus-aqua, which are cyanobacteria, , It was possible to effectively control over 90% of the cyanobacteria in the water system when the final concentrations were 0.2, 0.5 and 1 μM, respectively.
신규 화합물 22-4, 4-4, 4-3 및 18-4 등은 규조류인 스테파노디스커스 한츠치 등이 조류초기, 조류발전, 조류대발생 단계로 존재할 때 접종하여 최종농도가 각각 0.1, 0.2, 0.5 μM이 된다면 해당수계 내 규조류의 90% 이상을 효과적으로 제어가능하였다.The new compounds 22-4, 4-4, 4-3 and 18-4 were inoculated when the diatom Steptodiscus tsutsugi was present in the early stages of bird development, 0.5 μM, it was possible to effectively control over 90% of the diatoms in the water system.
신규 화합물 22-4 및 28 등은 와편모조인 페리디니움 바이패스 등이 조류초기, 조류발전, 조류대발생 단계로 존재할 때 접종하여 최종농도가 각각 0.5, 1, 2 μM이 된다면 해당수계 내 와편모조의 90% 이상을 효과적으로 제어가능하였다.The new compounds 22-4 and 28 are inoculated when peridinium bypass, which is a phallic mimic, is present at the beginning of the tidal flow, the tidal flow, and the tidal flora, and if the final concentrations are 0.5, 1 and 2 μM, More than 90% of the imitation can be effectively controlled.
이상의 결과를 통해, 현장에서 발생하는 녹조와 발전단계에 따라 적합한 신규 화합물의 선택과 접종량을 결정할 수 있음을 알 수 있다.
Based on the above results, it can be seen that the selection of the new compound and the inoculation amount can be determined according to the green tide and the development stage in the field.
실시예Example 4 : 4 : 생태독성Ecotoxicity 적용실험 Application experiment
실시예 3에서 사용된 화합물 중 가장 우수한 살조효과를 보유한 3종(04-4, 06-3, 40)의 신규 화합물을 대상으로 생태독성 적용실험을 미국 EPA 기준 생물 (지표조류, 지표동물플랑크톤)을 사용하여 측정하였다. 현장생태계 내 적용을 위해 부산광역시 금정구 회동저수지 선동교에 설치된 실험구를 이용하였다.Ecological toxicity tests were conducted on three new compounds (04-4, 06-3, 40) that have the best killing effect among the compounds used in Example 3, and were classified into US EPA standard organisms (indicator algae, surface zooplankton) . For the application in the field ecosystem, we used experimental sites installed in Sangdong Bridge, Dongdong Reservoir, Geumjeong - gu, Busan.
우선 지표조류의 경우, 지수성장 단계의 셀레나스트륨 카프리코너튬(Selenastrium capricornutum)을 준비하고 신규 화합물 04-4, 06-3, 40을 각각 접종하여 지표생물의 시작밀도와 접종농도가 각각 1 × 104 cells/ mL, 1000, 500, 200, 100, 50, 20, 10, 5, 2, 1, 0.5, 0.2, 0.1 μM이 되도록 준비하였다. 혼합 배양액은 지표생물의 최적성장 조건으로 배양되었다 (20℃, 50 μmol/m2s, EG:JM 배지, 12hr light : 12hr dark cycle). 12시간 단위로 실험예 1에서 언급한 것처럼 72시간 동안 광학현미경 하에서 지표생물의 개체수 변화를 직접 관찰하였다.In the case of the indicator algae, Selenastrium capricornutum (Selenastrium capricornutum) at the exponential growth stage was prepared and inoculated with new compounds 04-4, 06-3, and 40, respectively. The initial density and inoculum concentration of the indicator organisms were 1 × 10 4 cells / mL, 1000, 500, 200, 100, 50, 20, 10, 5, 2, 1, 0.5, 0.2, 0.1 μM. The mixed culture was cultured under optimal growth condition (20 ℃, 50 μmol / m2s, EG: JM medium, 12 hr light: 12 hr dark cycle). As shown in Experimental Example 1, the change in the population of indicator organisms was directly observed under an optical microscope for 72 hours in 12 hour units.
다음으로, 지표동물 플랑크톤의 경우, 태어난지 24시간이 경과하지 않은 동물플랑크톤(zooplankton) 다프니아 마그나(Daphnia magna) 성체를 10마리씩 3개의 반복구로 준비하고 신규 화합물 04-4, 06-3, 40을 각각 접종하여 시작농도가 1000, 500, 200, 100, 50, 20, 10, 5, 2, 1, 0.5, 0.2, 0.1 μM이 되도록 준비하였다. 배양조건은 25oC, 50 μmol/m2s, 12hr light : 12hr dark cycle의 배양조건으로 24시간 단위로 48시간 개체수 변화를 관찰하였다. 다프니아 마그나의 배양수로는 KCl 0.024g, MgSO4·7H2O 0.738g, CaSO4·7H2O 0.360g, NaHCO3 0.576g가 포함된 멸균수(DW) 3 L를 준비하였다. 상기 종의 관찰은 육안으로 직접 수행하여 기록해 주었다.Next, in the case of the surface zooplankton, zapplankton daphnia magna (adult zooplankton), which has not elapsed 24 hours after birth, is prepared in three repeats of 10 animals each, and new compounds 04-4, 06-3, and 40 100, 50, 20, 10, 5, 2, 1, 0.5, 0.2, and 0.1 μM, respectively. Cultivating conditions were observed at 24 hours and 48 hours in culture conditions of 25oC, 50 μmol / m2s, 12hr light: 12hr dark cycle. As a culture channel of Daphne Magna, 3 L of sterilized water (DW) containing 0.024 g of KCl, 0.738 g of MgSO4 占 H2O, 0.360 g of CaSO4 占 H2O and 0.576 g of NaHCO3 was prepared. Observation of the species was performed directly by visual observation.
마지막으로 지표어류의 경우 유수식 어류배양시스템을 설치하고 Zebrafish(Danio rerio)를 이용하여 14일 동안 0 개체의 사망률을 확인되도록 순응시킨 뒤, 2 ± 1 cm의 제브라피시를 선별하고 신규 화합물 04-4, 06-3, 40을 각각 접종하여 지표생물의 시작밀도와 접종농도가 각각 7 개체/3 L, 1000, 500, 200, 100, 50, 20, 10, 5, 2, 1, 0.5, 0.2, 0.1 μM이 되도록 준비하였다. 시험기간 동안 지수식으로 진행하여 시험액을 교환하지 않았으며, 먹이를 공급하지 않았다. 배양조건은 25oC, 50 μmol/m2s, 12hr light : 12hr dark cycle의 배양조건으로 12시간 단위로 96시간 지표생물 사망률과 기형변화를 육안으로 직접 관찰하였다.
Finally, in the case of surface fish, a water-based fish culture system was installed and adapted to confirm the mortality rate of 0 individuals for 14 days using Zebrafish (Danio rerio). Then, 2 ± 1 cm of zebrafish was selected, , 06-3 and 40 were inoculated respectively and the starting density and inoculation concentration of surface organisms were 7 individuals / 3 L, 1000, 500, 200, 100, 50, 20, 10, 5, 2, 1, 0.1 μM. During the test period, the test solution was not exchanged, and no food was fed. The culture conditions were 25oC, 50 μmol / m2s, 12hr light: 12hr dark cycle.
실험결과, 도 3에 나타난 바와 같이, 상기 화합물에 의한 지표생물 셀레나스트륨 카프리코너튬의 EC50 값은 최소 3.2 μM 이상으로 측정되어 상기 화합물(04-3, 06-3, 40)의 최대 접종량인 0.5 μM의 6.4 배에 해당하는 농도에서도 생존율이 50% 이상으로 유지되는 것으로 조사되었다.As shown in FIG. 3, the EC50 value of the indicator organism Selenium capricornorium by the above compound was measured to be at least 3.2 μM and the maximum dose of the compound (04-3, 06-3, 40) The survival rate was maintained at over 50% even at the concentration of 6.4 times of 0.5 μM.
다음으로 지표동물플랑크톤의 경우, 상기 화합물(04-3, 06-3, 40)의 EC50 값이 최소 14.5 μM 이상으로 측정되어 상기 화합물의 최대 접종량인 0.5 μM의 29 배에 해당하는 농도에서도 생존율이 50% 이상으로 유지되는 것으로 조사되었다.Next, in the case of the surface zooplankton, the EC50 value of the compound (04-3, 06-3, 40) was measured to be at least 14.5 μM, and the survival rate even at a concentration corresponding to 29 times the maximum inoculation amount of 0.5 μM 50% or more.
마지막으로 지표어류의 경우, 상기 화합물(04-3, 06-3, 40)의 EC50 값이 최소 15.7 μM 이상으로 측정되어 상기 화합물의 최대 접종량인 0.5 μM의 31.4 배에 해당하는 농도에서도 생존율이 50% 이상으로 유지되는 것으로 조사되었다. 전반적으로 신규 나프토퀴논의 경우 독성이 매우 낮은 친환경 화합물인 것으로 조사되었다.Finally, in the case of surface fishes, the EC50 value of the compound (04-3, 06-3, 40) was measured to be at least 15.7 μM, and the survival rate was 50% even at a concentration of 31.4 times the maximum inoculation amount of 0.5 μM Or more. Overall, the novel naphthoquinone was found to be an eco-friendly compound with very low toxicity.
이와 같이, 본 발명의 화합물이 독성이 매우 낮음을 확인할 수 있었다. Thus, it was confirmed that the compound of the present invention was very low in toxicity.
이러한 결과는 최적 접종량(≤ 0.5 μM)의 투여 시, 기존 살조제와는 다르게, 본 발명의 화합물은 독성이 적거나 없는 화합물로서 2차적인 환경오염을 최소화할 수 있다는 장점을 지닌다는 것을 의미한다.
These results indicate that the compound of the present invention has the advantage of minimizing secondary environmental pollution as a compound having little or no toxicity when administered at an optimal dose (≤ 0.5 μM) .
실시예Example 5 : 신규 화합물의 현장 적용실험 5: Field application of new compounds
실시예 4에서 급성 독성이 거의 없는 것으로 판단된 3종(04-4, 06-3, 40)의 신규 화합물을 대상으로 녹조가 발생된 현장생태계(부산 금정구 회동에 위치한 회동저수지 선동교 아래) 내 적용하여 녹조 제어효과를 측정하였다.In the case of the new compounds of the four species (04-4, 06-3, 40) which were judged to have little acute toxicity in Example 4, the on-site ecosystem in which green algae were generated And the effect of greenhouse control was measured.
우선 신규 화합물 04-4의 경우, 스테파노디스커스(Stephanodiscus spp.)의 밀도가 4 × 103 cells/mL 일 때 도 4와 같이 현장 내 실험구(20 ton 규모)를 설치하고 상기 화합물의 초기 접종농도가 200 nM이 되도록 접종하였다. 이후. 30일 동안 상기 화합물을 접종하지 않은 대조구와 처리구의 상기 유해조류의 세포수, chlorophyll-a 값, 투명도, 조류독소 등을 평가해 주었다.In case of the new compound 04-4, when the density of Stephanodiscus spp. Is 4 × 10 3 cells / mL, the in-situ experiment (20 ton scale) is installed as shown in FIG. 4 and the initial inoculation concentration Was 200 nM. after. The number of cells, chlorophyll-a value, transparency, algal toxin and the like of the harmful algae in the control and treatment groups in which the compound was not inoculated for 30 days were evaluated.
다음으로, 신규 화합물 6-3과 40의 경우, 마이크로시스티스(Microcystis spp.)와 아나배나(Anabaena spp.)의 밀도가 각각 2 × 104 cells/mL, 3 × 104 cells/mL 일 때 도 4와 같이 현장 내 실험구(100 ∼ 150 ton 규모)를 설치하고 상기 화합물의 초기 접종농도가 400 ∼ 500 nM이 되도록 접종하였다. 이후. 30일 동안 상기 화합물을 접종하지 않은 대조구와 처리구의 상기 유해조류의 세포수, chlorophyll-a 값, 투명도, 조류독소 등을 평가해 주었다.
Next, in the case of the new compounds 6-3 and 40, when the densities of Microcystis spp. And Anabaena spp. Are 2 x 10 4 cells / mL and 3 x 10 4 cells / mL, respectively As shown in FIG. 4, an in-situ experiment (100-150 ton scale) was set up and inoculated so that the initial inoculation concentration of the compound was 400-500 nM. after. The number of cells, chlorophyll-a value, transparency, algal toxin and the like of the harmful algae in the control and treatment groups in which the compound was not inoculated for 30 days were evaluated.
실험결과, 도 4 및 이하 표들에 나타난 바와 같이, 신규 화합물 04-4가 접종된 처리구에서 스테파노디스커스의 세포수가 시간의 흐름에 따라 크게 감소하여 접종 30일 째에 조류주의보가 해제수준까지 감소하였고 적용전 대비 적용후 91.7% 이상의 조류제거효과를 확인할 수 있었다. As shown in FIG. 4 and the following tables, the number of cells of Stephanos discus in the treated plants inoculated with the new compound 04-4 was greatly decreased with the passage of time, and the alertness of the birds was reduced to the release level on the 30th day of inoculation The effect of algae removal of 91.7% or more was confirmed after the application.
이에 투명도는 크게 개선되어 바닥수심까지 선명하게 관찰 가능하였다. 뿐만 아니라 클로로필 에이 값 또한 적용전 대비 적용후 93.3%까지 감소하였다.As a result, the transparency was greatly improved and the depth of the floor could be clearly observed. In addition, chlorophyll a was also decreased to 93.3% after application.
(표 6)(Table 6)
다음으로 신규 화합물 06-3의 경우, 마이크로시스티스를 대상으로 실험을 시작한 후 적용전 조류경보 수준의 마이크로스티스 세포수를 적용후 100%에 가까운 조류제거효과를 관찰할 수 있었으며, 투명도 또한 크게 개선되어 바닥까지 선명하게 관찰 가능하였다. 뿐만 아니라 클로로필 에이 값과 조류독소 또한 적용전 대비 적용후 93.8%와 50%까지 감소하였다.Next, in the case of the new compound 06-3, it was possible to observe the algae removal effect close to 100% after application of the microsyst cell number at the level of the algae alert level before the application, And it was possible to observe clearly to the bottom. In addition, chlorophyll a and tidal toxin were decreased to 93.8% and 50% after application.
(표 7)(Table 7)
마지막으로 40의 경우, 아나배나를 대상으로 실험을 시작한 후 적용전 조류주의보 수준의 아나배나 세포수를 적용후 100%에 가까운 조류제거효과를 관찰할 수 있었으며, 투명도 또한 크게 개선되어 바닥까지 선명하게 관찰 가능하였다. 뿐만 아니라 클로로필 에이 값과 조류독소 또한 적용전 대비 적용후 95%와 80%까지 감소하였다.Finally, in the case of 40, after the experiment was started for the anabnana, the algae removal effect close to 100% was observed after application of the anabuna cell number before the application, and the transparency was also greatly improved, Observable. In addition, chlorophyll a and tidal toxin were reduced to 95% and 80% after application.
(표 8)(Table 8)
이와 같이, 본 발명의 3가지 신규 화합물인 04-4, 06-3, 40 등은 200 ∼ 500 nM 이하의 초기 접종농도에서 실제 환경에서 발생한 담수산 유해조류에 의한 녹조를, 짧은 기간 내에 효과적으로 제어하여 부가적으로 클로로필 a 및 조류독소값 감소, 투명도 개선 등의 부가적인 효과를 얻을 수 있음을 확인하였다.
Thus, the three new compounds of the present invention, 04-4, 06-3, and 40, can effectively control the green algae caused by freshwater marine algae occurring in the actual environment at an initial inoculation concentration of 200 to 500 nM or less In addition, it was confirmed that chlorophyll - a and algal toxin value could be decreased and transparency could be improved.
즉, 상기 실험 결과로부터, 본 발명의 대표적인 화합물의 경우, 200 ∼ 500 nM에서도 대상 담수산 유해조류(조류경보수준 이하)를 100%까지 제어할 수 있음을 알 수 있고, 종래의 살조제와 견주어 비슷하거나 보다 우수한 살조활성을 보유하고 있음도 알 수 있었다.That is, from the above experimental results, it can be seen that the representative compounds of the present invention can control up to 100% of harmful algae (below the bird alert level) of the target freshwater fish even at 200 to 500 nM, It was also found that they had similar or better tidal activity.
본 발명의 화합물은 또한, 전력, 관리운영, 인력비가 소요되는 여타 녹조제어방법에 비해 무동력이며, 1, 2회식 살포형식으로 관리, 운영의 필요성이 없어 경제적인 상대적 우위를 가질 수 있음을 알 수 있다.
The compounds of the present invention are also less active than other greenhouse control methods that require power, management, and manpower, and can be economically advantageous in that they do not need to be managed and operated in a one- or two- have.
이제까지 본 발명에 대하여 그 바람직한 실시예들을 중심으로 살펴보았다. 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자는 본 발명이 본 발명의 본질적인 특성에서 벗어나지 않는 범위에서 변형된 형태로 구현될 수 있음을 이해할수 있을 것이다. 그러므로 개시된 실시예들은 한정적인 관점이 아니라 설명적인 관점에서 고려되어야 한다. 본 발명의 범위는 전술한 설명이 아니라 특허청구범위에 나타나 있으며, 그와 동등한 범위 내에 있는 모든 차이점은 본 발명에 포함된 것으로 해석되어야 할 것이다.The present invention has been described with reference to the preferred embodiments. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the spirit and scope of the invention as defined by the appended claims. Therefore, the disclosed embodiments should be considered in an illustrative rather than a restrictive sense. The scope of the present invention is defined by the appended claims rather than by the foregoing description, and all differences within the scope of equivalents thereof should be construed as being included in the present invention.
Claims (30)
[화학식 2] [화학식 3] [화학식 4]
[화학식 5] [화학식 6]
상기 [화학식 2] 내지 [화학식 6]에서,
R3는 피페리딘, CH=N, CH2-NH, NH 또는 S이고,
R4는 수소, 치환 또는 비치환된 탄소수 1 내지 12의 알킬기, 치환 또는 비치환된 탄소수 6 내지 18의 아릴기, 치환 또는 비치환된 탄소수 2 내지 18의 헤테로아릴기, 치환 또는 비치환된 탄소수 3 내지 18의 사이클로알킬기, 치환 또는 비치환된 탄소수 2 내지 18의 헤테로사이클로알킬기, 치환 또는 비치환된 탄소수 3 내지 18의 사이클로알케닐기 및 치환 또는 비치환된 탄소수 2 내지 18의 헤테로사이클로알케닐기 중에서 선택된다.
A harmful algae controlling composition comprising a compound represented by the following formulas (2) to (6) or a salt thereof as an active ingredient:
[Chemical Formula 2] < EMI ID =
[Chemical Formula 5]
In the above formulas 2 to 6,
R 3 is piperidine, CH = N, CH 2 -NH, NH or S,
R 4 represents hydrogen, a substituted or unsubstituted alkyl group having 1 to 12 carbon atoms, a substituted or unsubstituted aryl group having 6 to 18 carbon atoms, a substituted or unsubstituted heteroaryl group having 2 to 18 carbon atoms, a substituted or unsubstituted carbon number A substituted or unsubstituted cycloalkyl group having 3 to 18 carbon atoms, a substituted or unsubstituted heterocycloalkyl group having 2 to 18 carbon atoms, a substituted or unsubstituted cycloalkenyl group having 3 to 18 carbon atoms, and a substituted or unsubstituted heterocycloalkenyl group having 2 to 18 carbon atoms Is selected.
상기 R4가 치환된 탄소수 1 내지 12의 알킬기인 경우 H, O, N, S, Cl, F, OH 및 COOH 중에서 선택된 1종 이상의 치환기로 치환된 탄소수 1 내지 12의 알킬기인 것을 특징으로 하는 유해조류 제어용 조성물.
The method according to claim 1,
Is an alkyl group having 1 to 12 carbon atoms substituted with at least one substituent selected from H, O, N, S, Cl, F, OH and COOH when R 4 is an alkyl group having a substituted carbon number of 1 to 12 A composition for controlling algae.
상기 R4는 하기 [구조식 1] 중에서 선택되는 어느 하나인 것을 특징으로 하는 유해조류 제어용 조성물:
[구조식 1]
*-OCH3
상기 [구조식 1]에서,
R5는 O 또는 S이고,
R6은 수소, Cl, SO2-CH3, OCH3, NO2, OCH2CH3, F 또는 (CH3)p이며, 상기 p는 1 또는 2이며,
R7은 CH3 또는 NO2이고,
*는 상기 [화학식 2] 내지 [화학식 6]에 결합하는 위치를 표시한 것이다.
The method according to claim 1,
Wherein R 4 is any one selected from the following Structural Formula 1:
[Structural formula 1]
* -OCH 3
In the above formula 1,
R < 5 > is O or S,
R 6 is hydrogen, Cl, SO 2 -CH 3 , OCH 3 , NO 2 , OCH 2 CH 3 , F or (CH 3 ) p , p is 1 or 2,
And R 7 is CH 3 or NO 2,
* Represents the position of bonding to the above formulas (2) to (6).
상기 R4는 하기 [구조식 2] 중에서 선택되는 어느 하나인 것을 특징으로 하는 유해조류 제어용 조성물:
[구조식 2]
상기 [구조식 2]에서,
*는 상기 [화학식 2] 내지 [화학식 6]에 결합하는 위치를 표시한 것이다.
The method according to claim 1,
Wherein R 4 is any one selected from the following structural formulas:
[Structural formula 2]
In the above formula 2,
* Represents the position of bonding to the above formulas (2) to (6).
상기 R4는 하기 [구조식 3] 중에서 선택되는 어느 하나인 것을 특징으로 하는 유해조류 제어용 조성물:
[구조식 3]
상기 [구조식 3]에서,
n은 0 내지 11의 정수이고, R8은 CR9, OR10, NR11, NHR12 및 Cl로 이루어진 군중에서 선택되고, *는 상기 [화학식 2] 내지 [화학식 6]에 결합하는 위치를 표시한 것이며,
상기 CR9는 하기 [구조식 4] 중에서 선택되며, 하기 [구조식 4] 내에 표시된 *는 상기 R8에 결합하는 위치를 표시한 것이며,
[구조식 4]
*-CH3 *-COOH
상기 OR10은 하기 [구조식 5] 중에서 선택되고, 하기 [구조식 5] 내에 표시된 *는 상기 R8에 결합하는 위치를 표시한 것이며,
[구조식 5]
*-OH *-OCH3 *-OCH2CH2OH
상기 NR11은 하기 [구조식 6] 중에서 선택되고, 하기 [구조식 6] 내에 표시된 *는 상기 R8에 결합하는 위치를 표시한 것이며,
[구조식 6]
상기 NHR12는 하기 [구조식 7] 중에서 선택되고, 하기 [구조식 7] 내에 표시된 *는 상기 R8에 결합하는 위치를 표시한 것이다.
[구조식 7]
*-NHCH2CH3 *-NHCH2CH2OH
The method according to claim 1,
Wherein R 4 is any one selected from the following Structural Formula 3:
[Structural Formula 3]
In the above formula 3,
n is an integer of 0 to 11, and R 8 is selected from the group consisting of CR 9 , OR 10 , NR 11 , NHR 12 and Cl, and * represents the position to be bonded to the above formulas 2 to 6 However,
CR 9 is selected from the following [Formula 4], and * in the following [Formula 4] represents the position to which R 8 is bonded,
[Structural Formula 4]
* -CH 3 * -COOH
OR 10 is selected from the following [Structural Formula 5], * in the following [Structural Formula 5] is a position to which R 8 is bonded,
[Structural Formula 5]
* -OH * -OCH 3 * -OCH 2 CH 2 OH
Wherein NR 11 is selected from the following [Structural Formula 6], and * in the following [Structural Formula 6] is a position to which R 8 is bonded,
[Structural Formula 6]
NHR < 12 > is selected from the following [Structural Formula 7], and * in the following [Structural Formula 7] represents the position to which R < 8 >
[Structural Formula 7]
* -NHCH 2 CH 3 * -NHCH 2 CH 2 OH
상기 [화학식 2] 내지 [화학식 6]으로 표시되는 화합물은 하기 NQ01-1 내지 NQ49-p로 표시되는 화합물 중에서 선택되는 것을 특징으로 하는 유해조류 제어용 조성물:
NQ01-1 NQ01-2A
NQ01-4 NQ01-3
NQ01-6A NQ02-1
NQ02-2A NQ02-4
NQ02-3 NQ02-5
NQ03-1 NQ03-2A
NQ03-4 NQ03-3
NQ04-1 NQ04-2A
NQ04-4 NQ04-3
NQ05-1 NQ05-2A
NQ05-4 NQ05-3
NQ06-1 NQ06-2A
NQ06-4 NQ06-3
NQ07-1 NQ07-2A
NQ07-4 NQ07-3
NQ08-1 NQ08-2A
NQ08-4 NQ09-1
NQ09-2A NQ09-4
NQ09-3 NQ09-6A
NQ09-5 NQ10-1
NQ10-2A NQ10-4
NQ10-3 NQ10-6A
NQ10-5 NQ11-1
NQ11-2A NQ11-4
NQ11-3 NQ12-1
NQ12-2A NQ12-4
NQ12-3 NQ13-1
NQ13-2A NQ13-4
NQ13-3 NQ14-1
NQ14-2A NQ14-4
NQ14-3 NQ15-4
NQ15-3 NQ16-4
NQ16-3 NQ17-4
NQ17-3 NQ18-4
NQ18-3 NQ19-4
NQ19-3 NQ20-4
NQ20-3 NQ22-4
NQ22-3 NQ23
NQ24 NQ25
NQ26 NQ27
NQ28 NQ29
NQ30 NQ31
NQ32 NQ33
NQ34 NQ35
NQ36 NQ37
NQ38 NQ39
NQ40 NQ41
NQ42 NQ43
NQ44 NQ45
NQ46 NQ47
NQ48 NQ49
NQ50 NQ51
NQ52 NQ53
NQ54 NQ55
NQ38-p NQ40-p
NQ46-p NQ47-p
NQ49-p
The method according to claim 1,
The compounds represented by the above formulas (2) to (6) are selected from compounds represented by the following NQ01-1 to NQ49-p:
NQ01-1 NQ01-2A
NQ01-4 NQ01-3
NQ01-6A NQ02-1
NQ02-2A NQ02-4
NQ02-3 NQ02-5
NQ03-1 NQ03-2A
NQ03-4 NQ03-3
NQ04-1 NQ04-2A
NQ04-4 NQ04-3
NQ05-1 NQ05-2A
NQ05-4 NQ05-3
NQ06-1 NQ06-2A
NQ06-4 NQ06-3
NQ07-1 NQ07-2A
NQ07-4 NQ07-3
NQ08-1 NQ08-2A
NQ08-4 NQ09-1
NQ09-2A NQ09-4
NQ09-3 NQ09-6A
NQ09-5 NQ10-1
NQ10-2A NQ10-4
NQ10-3 NQ10-6A
NQ10-5 NQ11-1
NQ11-2A NQ11-4
NQ11-3 NQ12-1
NQ12-2A NQ12-4
NQ12-3 NQ13-1
NQ13-2A NQ13-4
NQ13-3 NQ14-1
NQ14-2A NQ14-4
NQ14-3 NQ15-4
NQ15-3 NQ16-4
NQ16-3 NQ17-4
NQ17-3 NQ18-4
NQ18-3 NQ19-4
NQ19-3 NQ20-4
NQ20-3 NQ22-4
NQ22-3 NQ23
NQ24 NQ25
NQ26 NQ27
NQ28 NQ29
NQ30 NQ31
NQ32 NQ33
NQ34 NQ35
NQ36 NQ37
NQ38 NQ39
NQ40 NQ41
NQ42 NQ43
NQ44 NQ45
NQ46 NQ47
NQ48 NQ49
NQ50 NQ51
NQ52 NQ53
NQ54 NQ55
NQ38-p NQ40-p
NQ46-p NQ47-p
NQ49-p
상기 NQ01-1 내지 NQ49-p로 표시되는 화합물 중에서 화합물 NQ01-4, NQ06-3, NQ40, NQ15-3, NQ02-3, NQ15-3, NQ19-4, NQ22-4, NQ40, NQ46, NQ47, NQ48 및 NQ49는 각각 남조강에 대해서 살조효과를 가지고,
상기 NQ01-1 내지 NQ49-p로 표시되는 화합물 중에서 화합물 NQ01-4, NQ02-3, NQ04-4, NQ04-3, NQ05-4, NQ09-4, NQ10-3, NQ15-4, NQ18-4, NQ22-4 및 NQ41은 각각 규조강에 대해서 살조효과를 가지며,
상기 NQ01-1 내지 NQ49-p로 표시되는 화합물 중에서 NQ22-4는 와편모조에 대해서 살조효과를 가지는 것을 특징으로 하는 유해조류 제어용 조성물.
13. The method of claim 12,
Among the compounds represented by NQ01-1 to NQ49-p, compounds NQ01-4, NQ06-3, NQ40, NQ15-3, NQ02-3, NQ15-3, NQ19-4, NQ22-4, NQ40, NQ46, NQ47, NQ48 and NQ49 have a killing effect on the southern steel, respectively,
Among the compounds represented by NQ01-1 to NQ49-p, compounds NQ01-4, NQ02-3, NQ04-4, NQ04-3, NQ05-4, NQ09-4, NQ10-3, NQ15-4, NQ18-4, NQ22-4 and NQ41 each have a killing effect on the diatomaceous steel,
Wherein the NQ22-4 among the compounds represented by NQ01-1 to NQ49-p has a killing effect on the bivalve mosquito.
상기 유해조류 제어용 조성물은 담수산 유해조류의 광합성 체계의 Q-사이트에 작용하여 광합성활성을 저해함을 특징으로 하는 유해조류 제어용 조성물.
The method according to claim 1,
Wherein said composition for controlling harmful birds acts on Q-site of photosynthetic system of freshwater marine algae to inhibit photosynthesis activity.
상기 유해조류는 남조강, 규조강, 녹조강, 유글레조강, 와편모조강, 황색편모조강, 갈색편모조강 및 홍조강 조류로 이루어진 군중에서 선택되고,
상기 남조강(Cyanophyceae) 조류는 마이크로시스티스(Microcystis), 아나베나(Anabaena), 아파니존메논(Aphanizomenon), 오실라토리아(Oscillatoria) 및 워로니키니아(Woronichinia) 속 조류로 이루어진 군중에서 선택되는 1종 이상이며,
상기 규조강(Bacillariophyceae) 조류는 스테파노디스커스(Stephanodiscus), 사이클로텔라(Cyclotella), 사이클로스테파노스(Cyclostaphanos), 아울라코세이라(Aulacoseira), 멜로지라(Melosira), 탈라지오지라(Thalassiosira), 케토세로스(Chaetoceros) 스켈레토네마(Skeletonema), 아크난테스(Achnanthes), 아스테리오넬라(Asterionella), 아칸토세라스(Acanthoceras), 나비큘라(Navicula), 니츠취아(Nitzschia), 디플로네시스(Diploneis), 심벨라(Cymbella), 곰포네마(Gomphonema), 수리렐라(Surirella), 시네드라(Synedra), 프레즐라리아(Fragilaria), 실린드로세카(Cylindrotheca), 유캄피아(Eucampia), 코스마리움(Cosmarium) 및 타벨라리아(Tabellaria) 속 조류로 이루어진 군중에서 선택되는 1종 이상이고,
상기 녹조강(Chlorophyceae) 조류는 클로스테리옵시스(Closteriopsis), 클로스테리움(Closterium), 하이드로테카(Hydrotheca), 스피로기라(Spirogyra), 고나토지곤(Gonatozygon), 액티나스트륨(Actinastrum), 마이크락티니움(Micractinium), 라걸헤이미어(Lagerheimia), 웨스텔라(Westella), 유도리나(Eudorina), 판도리나(Pandorina), 볼복스(Volvox), 딕티오스페리움(Dictyospaerium), 클라로코쿰(Chlorococcum), 보트리오코쿠스(Botryococcus), 스타우라스트륨(Staurastrum), 클로스테리움(Closterium), 모노라피디움(Monoraphidium), 안키스트로데스무스(Ankistrodesmus), 컬크네리엘라(Kirchneriella), 페디아스트룸(Pediastrum), 세네데스무스(Scenedesmus), 코엘라스트륨(Coelastrium), 클라미도모나스(Clamydomonas) 및 클로렐라(Chlorella) 속 조류로 이루어진 군중에서 선택되는 1종 이상이며,
상기 유글레나조강(Euglenophyceae) 조류는 트라켈로모나스(Trachelomonas), 파커스(Phacus) 및 유글레나(Euglena) 속 조류로 이루어진 군중에서 선택되는 1종 이상이고,
상기 와편모조강(Dinophyceae) 조류는 페리디늄(Peridinium) 또는 세라티움(Ceratium) 속 조류이며,
상기 황색편모조강(Chrysophyceae) 조류는 디노브리온(Dinobryon), 유로글레나(Uroglena), 시누라(Synura) 및 말로모나스(Mallomonas) 속 조류로 이루어진 군중에서 선택되는 1종 이상이고,
상기 홍조강(Phodophyceae) 조류는 로도모나스(Rhodomonas) 속 조류이며,
상기 갈색편모조강(Cryptophyceae) 조류는 크립토모나스(Cryptomonas) 조류인 것을 특징으로 하는 유해조류 제어용 조성물.
The method according to claim 1,
The harmful algae are selected from the group consisting of Namchogang, Diatomaceous River, Green River, Yugurejo River, Wrapped Imitation River, Yellow Copper Crude Steel,
Wherein the Cyanophyceae alga is selected from the group consisting of Microcystis, Anabaena, Aphanizomenon, Oscillatoria and Woronichinia birds. More than species,
The Bacillariophyceae algae may be selected from the group consisting of Stephanodiscus, Cyclotella, Cyclostaphanos, Aulacoseira, Melosira, Thalassiosira, Chaetoceros Skeletonema, Achnanthes, Asterionella, Acanthoceras, Navicula, Nitzschia, Diploneis, Cymbella, Gomphonema, Surirella, Synedra, Fragilaria, Cylindrotheca, Eucampia, Kosumerium, Crombie, Cosmarium and Tabellaria birds, and more preferably,
The Chlorophyceae algae may be selected from the group consisting of Closteriopsis, Closterium, Hydrotheca, Spirogyra, Gonatozygon, Actinastrum, And may be used in conjunction with other devices such as Micractinium, Lagerheimia, Westella, Eudorina, Pandorina, Volvox, Dictyospaerium, Such as Chlorococcum, Botryococcus, Staurastrum, Closterium, Monoraphidium, Ankistrodesmus, Kirchneriella, At least one selected from the group consisting of Pediastrum, Scenedesmus, Coelastrium, Clamydomonas and Chlorella species,
The Euglenophyceae alga is at least one selected from the group consisting of Trachelomonas, Phacus and Euglena birds,
The Dinophyceae alga is a peridinium or Ceratium algae,
The yellow Chrysophyceae bird is at least one selected from the group consisting of Dinobryon, Uroglena, Synura and Mallomonas birds,
The above-mentioned Phodophyceae bird is a Rhodomonas bird,
Wherein the brown algae Cryptophyceae is a Cryptomonas algae.
상기 남조강(Cyanophyceae) 조류는 마이크로시스티스(Microcystis) 또는 아나베나(Anabaena) 속 조류인 것을 특징으로 하는 유해조류 제어용 조성물.
18. The method of claim 17,
Wherein the Cyanophyceae alga is a microcystis or anabaena species bird.
상기 규조강(Bacillariophyceae) 조류는 스테파노디스커스(Stephanodiscus), 사이클로텔라(Cyclotella) 또는 아울라코세이라(Aulacoseira)인 것을 특징으로 하는 유해조류 제어용 조성물.
18. The method of claim 17,
Wherein the diatomite (Bacillariophyceae) bird is Stephanodiscus, Cyclotella or Aulacoseira.
A composition for controlling harmful birds comprising a compound represented by the general formulas (2) to (6) according to (1) or a salt thereof as an active ingredient is treated in an area in which harmful algae are present or in areas where signs of occurrence are observed A method of controlling harmful algae comprising.
상기 처리는 선박을 이용하여 국부적으로 살포하는 형태로 이루어지는 것을 특징으로 하는 유해조류 제어방법.
29. The method of claim 28,
Wherein the treatment is performed in a form of spraying locally using a ship.
상기 [화학식 2] 내지 [화학식 6]으로 표시되는 화합물 또는 그의 염을 최종농도가 0.2 μM ~ 100 μM이 되도록 처리하는 것을 특징으로 하는 유해조류의 제어방법.29. The method of claim 28,
Wherein the compound represented by any one of the above Chemical Formulas 2 to 6 or its salt is treated to have a final concentration of 0.2 μM to 100 μM.
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