KR101603324B1 - Method for preparation of 3-alkylthio-2-bromopyridine - Google Patents
Method for preparation of 3-alkylthio-2-bromopyridine Download PDFInfo
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Abstract
본 발명은 본 발명은 우수한 제초활성을 나타내는 플루오로알킬피리딘-설포닐우레아 유도체를 제조하기 위한 핵심 중간체인 피리딘 화합물의 새로운 제조방법, 그리고 이때 사용된 신규 알킬티오올레핀 유도체 및 이의 제조방법에 관한 것으로, 본 발명에 따른 신규 화학식 (2)의 알킬티오올레핀 유도체를 이용하는 방법에 의하면, 플루세토설푸론의 제조 중간체인 화학식 (1)의 화합물을 초저온 반응의 적용 없이 보다 훨씬 단순한 공정 단계를 통해 종래의 방법보다 높거나 동등 수준의 수율로 제조할 수 있다.
[화학식 1]
[화학식 2]
상기 식에서, A 및 X는 발명의 상세한 설명에 정의된 바와 같다.The present invention relates to a novel process for preparing pyridine compounds as key intermediates for the production of fluoroalkylpyridine-sulfonylurea derivatives having excellent herbicidal activity, and novel alkylthiolefin derivatives and processes for their preparation , The method using the alkylthiolefin derivative of the novel formula (2) according to the present invention makes it possible to produce the compound of formula (1), which is the intermediate for the production of flutosulfuron, through a much simpler process step than the application of the cryogenic reaction, Method can be produced at a higher or equivalent yield.
[Chemical Formula 1]
(2)
Wherein A and X are as defined in the Detailed Description of the Invention.
Description
본 발명은 우수한 제초활성을 나타내는 플루오로알킬피리딘-설포닐우레아 유도체를 제조하기 위한 핵심 중간체인 피리딘 화합물의 새로운 제조방법, 그리고 이때 사용된 신규 알킬티오올레핀 유도체 및 이의 제조방법에 관한 것이다.The present invention relates to a novel process for preparing pyridine compounds as core intermediates for the production of fluoroalkylpyridine-sulfonylurea derivatives having excellent herbicidal activity, and novel alkylthiolefin derivatives and processes for their preparation.
다음 화학식 (1)의 피리딘 화합물은 우수한 제초 활성을 지닌 플루세토설푸론(flucetosulfuron)의 합성을 위한 핵심 중간체로서 본 출원인에 의해 특허 출원되었다(PCT/KR2013/006269).The following pyridine compounds of formula (1) have been patented by the applicant (PCT / KR2013 / 006269) as key intermediates for the synthesis of flucetosulfuron with excellent herbicidal activity.
[화학식 1][Chemical Formula 1]
상기 식에서,In this formula,
A는 C3-C5-알킬 또는 C3-C6사이클로알킬을 나타내거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 벤질을 나타낸다.A is C 3 -C 5 - alkyl or C 3 -C 6, or represent cycloalkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - by a substituent selected from alkoxy of 1 to 5, a substituted or unsubstituted benzyl .
화학식 (1)의 화합물은 화학식 (3)의 화합물을 화학식 (4)의 리튬 아마이드류의 강염기와 반응시킨 후, 화학식 (5)의 친전자체 화합물과 반응시키는 방법에 의해 제조될 수 있다.The compound of the formula (1) can be prepared by reacting the compound of the formula (3) with a strong base of the lithium amide of the formula (4) and then reacting it with the electrophile of the formula (5).
[화학식 3](3)
[화학식 4][Chemical Formula 4]
[화학식 5][Chemical Formula 5]
A-S-XA-S-X
상기 식에서,In this formula,
n = 0 또는 3을 나타내며, n represents 0 or 3,
A는 C3-C5-알킬 또는 C3-C6사이클로알킬을 나타내거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 벤질을 나타내며,A is C 3 -C 5 - alkyl or C 3 -C 6, or represent cycloalkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - by a substituent selected from alkoxy of 1 to 5, a substituted or unsubstituted benzyl Lt; / RTI >
X는 염소 원자 또는 S-A 기를 나타내며, 특히, X가 S-A 기를 나타내는 경우 화학식 (5)의 화합물은 하기 화학식 (5a)의 대칭구조의 다이설파이드 화합물을 이루게 된다.X represents a chlorine atom or a S-A group, and in particular, when X represents an S-A group, the compound of the formula (5) forms a disulfide compound of a symmetrical structure of the following formula (5a).
[화학식 5a][Chemical Formula 5a]
A-S-S-AA-S-S-A
이 과정에서 화학식 (4) 화합물의 리튬 아마이드류 강염기를 사용하는 반응을 위해서는 -78 ℃ 이하의 초저온 조건이 필요하다는 단점이 있다. 또한, 강염기가 작용하여 수소원자를 떼어낼 때 피리딘 고리의 3번 위치 수소원자뿐 아니라 4번 위치 수소원자도 떼어내어 3번과 4번 위치에 동시에 친전자체가 도입되어 화학식 (6)의 부성분이 5~10% 정도 생성되는 문제도 있다. In this process, there is a disadvantage that an extremely low temperature condition of -78 캜 or less is required for the reaction using the lithium amide strong base of the compound of formula (4). In addition, when a strong base acts to remove the hydrogen atom, not only the hydrogen atom at the 3-position of the pyridine ring but also the hydrogen atom at the 4-position are removed and the electrophile is simultaneously introduced at positions 3 and 4, There is also a problem that about 5 ~ 10% is generated.
[화학식 6][Chemical Formula 6]
여기에서, A는 전술한 바와 같다.Here, A is as described above.
한편, 화학식 (7)의 1,1,3,3-테트라메톡시프로판과 화학식 (8)의 아세토나이트릴 화합물로부터 얻게 되는 화학식 (9)의 시아노-다이엔 중간체 화합물을 브롬화수소/아세트산 용액과 반응시키는 것에 의해 초저온 반응 조건 없이 화학식 (10)의 2-브로모피리딘 고리를 직접 만드는 반응이 보고되었다(J. Org. Chem. 39, 3436 (1974); EP 323881 (1989)).On the other hand, the cyano-diene intermediate compound of the formula (9) obtained from 1,1,3,3-tetramethoxypropane of the formula (7) and the acetonitrile compound of the formula (8) was dissolved in a hydrogen bromide / acetic acid solution (10) in the absence of a cryogenic reaction condition (J. Org. Chem. 39, 3436 (1974); EP 323881 (1989)).
[화학식 7](7)
[화학식 8][Chemical Formula 8]
[화학식 9][Chemical Formula 9]
[화학식 10][Chemical formula 10]
여기에서, EWG는 전자를 당기는 효과를 갖는 작용기를 나타내며, 구체적으로는 알킬에스테르, 시아노, 알킬설폰기를 나타낸다.Here, EWG represents a functional group having an effect of attracting electrons, specifically, an alkyl ester, a cyano, or an alkylsulfone group.
위 반응을 도식화 하여 나타내면 다음 반응식 (1)과 같다.The above reaction can be represented schematically as shown in the following reaction formula (1).
[반응식 1][Reaction Scheme 1]
한편, 전자를 당기는 힘이 약한 트라이플루오로메틸티오기로 치환된 화학식 (11)의 아세토나이트릴의 경우에도 화학식 (7)의 1,1,3,3-테트라메톡시프로판과 반응하여 시아노-다이엔 유도체를 합성하는 예가 알려져 있다. 그러나, 이 경우에는 화학식 (12)의 시아노-다이엔 유도체에 화학식(13)의 화합물이 혼재하며 수율도 매우 낮다는 문제가 보고되었다(유럽특허 EP 0014893 A2).On the other hand, in the case of acetonitrile of the formula (11) in which the electron withdrawing group is substituted with a weakly trifluoromethylthio group, it is also possible to react with 1,1,3,3-tetramethoxypropane of the formula (7) An example of synthesizing a diene derivative is known. However, in this case, it has been reported that the compound of the formula (13) is mixed with the cyano-diene derivative of the formula (12) and the yield is very low (European Patent EP 0014893 A2).
[화학식 11](11)
[화학식 12][Chemical Formula 12]
[화학식 13][Chemical Formula 13]
위 반응을 도식화하여 나타내면 다음 반응식 (2)와 같다.The above reaction can be represented schematically by the following reaction formula (2).
[반응식 2][Reaction Scheme 2]
위 반응식 (2)와 동일한 조건에서 화학식 (11)의 아세토나이트릴 화합물 대신 단순한 화학식 (14)의 알킬티오아세토나이트릴을 사용한 경우에는, 메틸렌 주변의 전자 당김이 훨씬 더 약해져 반응이 전혀 진행되지 않는다.In the case of using the alkylthioacetonitrile of the formula (14) instead of the acetonitrile compound of the formula (11) under the same conditions as in the above reaction formula (2), the electron withdrawing around the methylene is much weaker and the reaction does not proceed at all .
[화학식 14][Chemical Formula 14]
여기에서, A는 C3-C5-알킬 또는 C3-C6사이클로알킬을 나타내거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 벤질을 나타낸다.Here, A is a C 3 -C 5 - alkyl or C 3 -C 6, or represent cycloalkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - alkoxy substituted by 1 to 5 substituents selected from or unsubstituted Gt; benzyl < / RTI >
본 발명자들은 위와 같은 문제점을 고려하여, 플루세토설푸론의 제조에 있어 핵심 중간체인 화학식 (1)의 화합물을 초저온 반응기를 사용하지 않고 제조할 수 있는 방법을 모색하여, 반응성이 약한 화학식 (14)의 알킬티오아세토나이트릴을 사용하면서도 보다 간편하고 높은 순도로 목적 화합물을 제조하고자 집중적인 연구를 수행하였으며, 그 결과 신규 알킬티오올레핀 유도체 화합물을 브롬화수소와 반응시켜 극저온의 반응 조건 없이 피리딘의 3번 위치에 알킬티오 치환기를 갖는 화학식 (1)의 피리딘 유도체를 합성하는 방법을 고안하였다. 또한, 이때 사용된 신규 화합물은 알킬티오기의 전자당김 능력이 떨어져 기존의 방법으로는 제조할 수 없으므로, 이의 제조 방법 역시 새로 개발함으로써 본 발명을 완성하게 되었다.In view of the above problems, the present inventors have sought a method of preparing a compound of formula (1), which is a key intermediate in the production of flutosulfuron, without using a cryogenic reactor, The present inventors have conducted intensive studies in order to produce a target compound with simpler and higher purity while using an alkylthioacetonitrile as a starting material. As a result, a novel alkylthiolefin derivative compound is reacted with hydrogen bromide, A pyridine derivative of the formula (1) having an alkylthio substituent at the position of the pyridine derivative is devised. In addition, since the novel compound used at this time has low electron withdrawing ability of the alkylthio group, it can not be prepared by the conventional method.
본 발명의 목적은 제초제로서 유용한 플루세토설푸론의 핵심 제조 중간체 화합물의 신규 제조방법을 제공하는 것이다.It is an object of the present invention to provide a novel method for preparing a core production intermediate compound of flutosulfuron useful as a herbicide.
본 발명의 다른 목적은 상기 제조 중간체 화합물의 제조에 사용되는 신규의 알킬티오올레핀 유도체 및 이의 제조방법을 제공하는 것이다.Another object of the present invention is to provide novel alkylthiolefin derivatives used in the preparation of said intermediate compounds and their preparation.
상기 목적을 달성하기 위하여 본 발명에서는, 플루세토설푸론의 제조에 있어 핵심 중간체인 화학식 (1)의 피리딘 유도체의 제조에 사용하기 위한 화학식 (2)의 알킬티오올레핀 유도체 화합물을 제공한다.In order to achieve the above object, the present invention provides an alkylthiolefin derivative compound of formula (2) for use in the production of a pyridine derivative of formula (1), which is a key intermediate in the production of flutosulfuron.
상기 식에서,In this formula,
A는 C3-C5-알킬 또는 C3-C6사이클로알킬을 나타내거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 벤질을 나타내고,A is C 3 -C 5 - alkyl or C 3 -C 6, or represent cycloalkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - by a substituent selected from alkoxy of 1 to 5, a substituted or unsubstituted benzyl Lt; / RTI >
X는 사이클릭 이차 아민 또는 R1R2N의 이차 아민을 나타내며, 이때 R1 및 R2는 각각 독립적으로 C1~C3 알킬이거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 페닐을 나타낸다.X represents a secondary amine or cyclic secondary amine R 1 R 2 N, wherein R 1 and R 2 are each independently a C 1 ~ C 3 alkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - ≪ / RTI > alkoxy, < RTI ID = 0.0 > and / or < / RTI >
바람직하게는, 사이클릭 이차 아민은 피롤리딘, 피페리딘 및 모폴린으로부터 선택될 수 있고, R1R2N의 이차 아민의 R1 및 R2 는 각각 독립적으로 메틸, 에틸, 프로필 및 페닐로부터 선택되거나, 메틸, 에틸, 메톡시 및 에톡시 중에서 선택된 치환체에 의해 1 내지 5 치환된 페닐로부터 선택될 수 있다. Preferably, the cyclic secondary amine is pyrrolidine, piperidine, and may be selected from morpholinyl, R 1 R of the secondary amine of the R 2 N 1 and R 2 are each independently methyl, ethyl, propyl, and phenyl Lt; / RTI > or phenyl substituted by one to five substituents selected from methyl, ethyl, methoxy and ethoxy.
바람직한 화학식 (2) 화합물은 2-(벤질설파닐)-5-[메틸(페닐)아미노]펜타-2,4-다이엔나이트릴, 2-(t-부틸설파닐)-5-[메틸(페닐)아미노]펜타-2,4-다이엔나이트릴, 5-[메틸(페닐)아미노]-2-(프로판-2-일설파닐)펜타-2,4-다이엔나이트릴, 5-[메틸(4-메톡시페닐)아미노]-2-(프로판-2-일설파닐)펜타-2,4-다이엔나이트릴, 5-[메틸(4-에톡시페닐)아미노]-2-(프로판-2-일설파닐)펜타-2,4-다이엔나이트릴, 2-(벤질설파닐)-5-[에틸(페닐)아미노]펜타-2,4-다이엔나이트릴, 2-(벤질설파닐)-5-[프로틸(페닐)아미노]펜타-2,4-다이엔나이트릴, 2-(벤질설파닐)-5-[메틸(4-메틸페닐)아미노]펜타-2,4-다이엔나이트릴, 5-(피페리딘-1-일)-2-(프로판-2-일설파닐)펜타-2,4-다이엔나이트릴, 2-(벤질설파닐)-5-(피페리딘-1-일)펜타-2,4-다이엔나이트릴, 2-(t-부틸설파닐)-5-(피페리딘-1-일)펜타-2,4-다이엔나이트릴, 2-(벤질설파닐)-5-(다이메틸아미노)펜타-2,4-다이엔나이트릴, 2-(벤질설파닐)-5-(다이에틸아미노)펜타-2,4-다이엔나이트릴, 2-(벤질설파닐)-5-(다이프로필아미노)펜타-2,4-다이엔나이트릴, 2-(t-부틸설파닐)-5-(다이메틸아미노)펜타-2,4-다이엔나이트릴, 5-(다이메틸아미노)-2-(프로판-2-일설파닐)펜타-2,4-다이엔나이트릴, 2-(벤질설파닐)-5-(모폴린-4-일)펜타-2,4-다이엔나이트릴, 2-(t-부틸설파닐)-5-(모폴린-4-일)펜타-2,4-다이엔나이트릴, 및 5-(모폴린-4-일)-2-(프로판-2-일설파닐)펜타-2,4-다이엔나이트릴을 예로 들 수 있다.A preferred compound of formula (2) is 2- (benzylsulfanyl) -5- [methyl (phenyl) amino] penta-2,4-dienonitrile, 2- Phenyl) amino] penta-2,4-dienonitrile, 5- [methyl (phenyl) amino] -2- (4-methoxyphenyl) amino] -2- (2-methoxyphenyl) amino] -2- (Phenyl) amino] penta-2,4-dienonitrile, 2- (4-fluorophenyl) 2- (benzylsulfanyl) -5- [methyl (4-methylphenyl) amino] penta-2,4-diazatricyclo [ 2-ylsulfanyl) penta-2,4-dienonitrile, 2- (benzylsulfanyl) -5- (piperidin- (Piperidin-1-yl) penta-2,4-dienenitrile, 2- (t-butylsulfanyl) Reil, 2- (benzyl (Dimethylamino) penta-2,4-dienonitrile, 2- (benzylsulfanyl) -5- (diethylamino) penta-2,4- Benzylsulfanyl) -5- (dipropylamino) penta-2,4-dienenitrile, 2- (t-butylsulfanyl) -5- (dimethylamino) penta-2,4- , 5- (dimethylamino) -2- (propan-2-ylsulfanyl) penta-2,4-dienonitrile, 2- (benzylsulfanyl) (Morpholin-4-yl) penta-2,4-dienenitrile, and 5- (morpholin- Yl) -2- (propane-2-ylsulfanyl) penta-2,4-dienonitrile.
더욱 바람직한 화학식 (2) 화합물은 5-[메틸(페닐)아미노]-2-(프로판-2-일설파닐)펜타-2,4-다이엔나이트릴, 5-(피페리딘-1-일)-2-(프로판-2-일설파닐)펜타-2,4-다이엔나이트릴, 5-(다이메틸아미노)-2-(프로판-2-일설파닐)펜타-2,4-다이엔나이트릴 및 5-(모폴린-4-일)-2-(프로판-2-일설파닐)펜타-2,4-다이엔나이트릴을 예로 들 수 있다.A more preferred compound of formula (2) is the compound of formula (I) which is 5- [methyl (phenyl) amino] -2- (propane- 2-ylsulfanyl) penta-2,4-diene nitrile, 5- (dimethylamino) -2- (propan- Enantiomer and 5- (morpholin-4-yl) -2- (propan-2-ylsulfanyl) penta-2,4-dienonitrile.
본 발명의 다른 목적을 달성하기 위한 화학식 (2) 화합물의 제조방법은, 하기 화학식 (14)의 화합물과 화학식 (15)의 화합물을 용매 중에서 유기산 및 유기염기와 동시에 반응시키는 것을 특징으로 한다.The method for preparing the compound of formula (2) for achieving another object of the present invention is characterized in that the compound of the formula (14) and the compound of the formula (15) are simultaneously reacted with an organic acid and an organic base in a solvent.
[화학식 2](2)
[화학식 14][Chemical Formula 14]
[화학식 15][Chemical Formula 15]
상기 식에서, A는 C3-C5-알킬 또는 C3-C6사이클로알킬을 나타내거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 벤질을 나타내고,Wherein, A is C 3 -C 5 - alkyl or C 3 -C 6, or represent cycloalkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - 1 to 5 is substituted by a substituent selected from alkoxy or beach Benzyl,
X는 사이클릭 이차 아민 또는 R1R2N의 이차 아민을 나타내며, 이때 R1 및 R2는 각각 독립적으로 C1~C3 알킬이거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 페닐을 나타낸다.X represents a secondary amine or cyclic secondary amine R 1 R 2 N, wherein R 1 and R 2 are each independently a C 1 ~ C 3 alkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - ≪ / RTI > alkoxy, < RTI ID = 0.0 > and / or < / RTI >
본 발명에 따른 화학식 (2) 화합물은, 화학식 (14) 화합물의 알킬티오기의 전자당김 능력이 현저히 떨어지기 때문에 앞서의 반응식 (1) 또는 (2)의 방법에 의해서는 제조될 수 없지만, 화학식 (15)의 아크롤레인 유도체와의 직접적인 노브나겔 축합 반응에 의해서는 얻을 수 있다.The compound of the formula (2) according to the present invention can not be produced by the method of the above-mentioned reaction formula (1) or (2) because the electron-withdrawing ability of the alkylthio group of the compound of the formula (14) Can be obtained by a direct knuckle condensation reaction with an acrolein derivative of the compound (15).
본 발명의 또 다른 목적을 달성하기 위한 플루세토설푸론의 제조 중간체인 화학식 (1)의 피리딘 유도체 화합물의 제조 방법은, 화학식 (2) 화합물을 용매 중에서 브롬화수소와 반응시키는 것을 특징으로 한다.A process for producing a pyridine derivative compound of formula (1), which is an intermediate for the production of flutosulfuron to achieve still another object of the present invention, is characterized in that the compound of formula (2) is reacted with hydrogen bromide in a solvent.
[화학식 1][Chemical Formula 1]
[화학식 2](2)
상기 식에서,In this formula,
A는 C3-C5-알킬 또는 C3-C6사이클로알킬을 나타내거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 벤질을 나타내고,A is C 3 -C 5 - alkyl or C 3 -C 6, or represent cycloalkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - by a substituent selected from alkoxy of 1 to 5, a substituted or unsubstituted benzyl Lt; / RTI >
X는 사이클릭 이차 아민 또는 R1R2N의 이차 아민을 나타내며, 이때 R1 및 R2는 각각 독립적으로 C1~C3 알킬이거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 페닐을 나타낸다.X represents a secondary amine or cyclic secondary amine R 1 R 2 N, wherein R 1 and R 2 are each independently a C 1 ~ C 3 alkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - ≪ / RTI > alkoxy, < RTI ID = 0.0 > and / or < / RTI >
이하, 본 발명을 더욱 구체적으로 설명한다.Hereinafter, the present invention will be described more specifically.
먼저, 본 발명에 따른 플루세토설푸론 제조 중간체인 화학식 (1) 화합물의 제조 방법은, 화학식 (2) 화합물을 용매 중에서 브롬화수소와 고리화 반응시키는 단계로 이루어진다. 이를 도식화 하면 반응식 (3)과 같다.First, the process for preparing the compound of formula (1), which is an intermediate for producing flutosulfuron according to the present invention, comprises the step of cyclizing the compound of formula (2) with hydrogen bromide in a solvent. This can be expressed as in equation (3).
[반응식 3][Reaction Scheme 3]
상기 식에서, A 및 X는 위에서 정의된 바와 같다.Wherein A and X are as defined above.
구체적인 반응 조건에 대해 자세히 설명하면 다음과 같다. 이 반응에서 브롬화수소는 적절한 용매 중에서 기체 브롬화수소를 사용하거나 아세트산에 녹인 브롬화수소 용액을 사용할 수 있다. 브롬화수소의 당량은 과량으로 사용하는 것이 바람직하며, 더욱 바람직하게는 3 내지 5 당량을 사용한다. 반응 온도는 0 내지 40 ℃의 범위에서 수행 가능하며, 5 내지 25 ℃ 범위가 바람직하고, 5 내지 15 ℃ 범위가 더욱 바람직하다.Specific reaction conditions will be described in detail as follows. In this reaction, hydrogen bromide can be either gaseous hydrogen bromide in an appropriate solvent or a hydrogen bromide solution dissolved in acetic acid. The equivalent amount of hydrogen bromide is preferably used in an excess amount, more preferably 3 to 5 equivalents. The reaction temperature may be in the range of 0 to 40 캜, preferably in the range of 5 to 25 캜, more preferably in the range of 5 to 15 캜.
기체 브롬화수소를 직접 사용할 경우, 화학식 (2)의 화합물을 용해시킨 용액에 기체 브롬화수소를 통과시킨다. 아세트산에 녹인 브롬화수소 용액을 사용할 경우에는, 화학식 (2)의 화합물을 용해시킨 용액에 브롬화수소/아세트산 용액을 투입하거나 순서를 바꾸어 브롬화수소/아세트산 용액에 화학식 (2)의 화합물을 용해시킨 용액을 투입할 수 있다.When gaseous hydrogen bromide is used directly, gaseous hydrogen bromide is passed through a solution in which the compound of formula (2) is dissolved. In the case of using a hydrogen bromide solution dissolved in acetic acid, a solution obtained by dissolving the compound of the formula (2) in a hydrogen bromide / acetic acid solution by changing the order or changing the hydrogen bromide / acetic acid solution into a solution in which the compound of the formula (2) Can be input.
이 반응에서 용매는 스스로 반응에 참여하지 않는 통상의 용매를 사용할 수 있으며, 바람직하게는 메탄올, 에탄올 등의 알코올류, 벤젠, 톨루엔, 크실렌 등의 방향족 탄화수소류, 테트라하이드로퓨란, 또는 디클로로메탄 등의 용매를 사용한다. 또는 출발물질인 화학식 (2)의 화합물을 제조할 때 사용한 용매를 그대로 사용할 수도 있다. The solvent used in this reaction may be a conventional solvent which does not participate in the reaction itself, preferably an alcohol such as methanol or ethanol, an aromatic hydrocarbon such as benzene, toluene or xylene, tetrahydrofuran or dichloromethane or the like Solvent is used. Alternatively, the solvent used in the preparation of the compound of formula (2) as a starting material may be used as it is.
본 발명에 따른 화학식 (1) 화합물의 제조방법에 사용되는 화학식 (2)의 화합물은 신규 구조의 알킬티오올레핀 유도체로서, 본 발명에서는 화학식 (2) 화합물과 이의 제조방법을 제공한다.The compound of formula (2) used in the process for preparing the compound of formula (1) according to the present invention is an alkylthiolefin derivative of novel structure, and the present invention provides a compound of formula (2) and a process for its preparation.
본 발명에 따른 화학식 (2)의 화합물은, 화학식 (14) 화합물과 화학식 (15) 화합물을 유기산 및 유기염기와 함께 용매를 환류하여 노브나겔 축합반응을 통해 제조할 수 있다(Name Reactions and Reagents in Organic Synthesis, Mundy, B. P.; Ellerd, M. G. John Wiley & Sons, Inc. 1988). 이를 도식화하면 반응식 (4)와 같다.The compound of the formula (2) according to the present invention can be prepared by refluxing the solvent of the compound of the formula (14) and the compound of the formula (15) together with an organic acid and an organic base, Organic Synthesis, Mundy, BP, Ellerd, MG John Wiley & This can be expressed as in equation (4).
[반응식 4][Reaction Scheme 4]
상기 식에서, A 및 X는 위에서 정의한 바와 같다.Wherein A and X are as defined above.
구체적인 반응 조건에 대해 자세히 설명하면 다음과 같다. 이 반응에서 용매는 스스로 반응에 참여하지 않는 통상의 용매를 사용할 수 있으며, 바람직하게는 벤젠, 톨루엔, 크실렌 등 방향족 탄화수소류를 사용한다. 이때 용매를 환류시키면서 물을 제거할 수 있는 반응 온도를 유지한다. 첨가제로서는 아세트산, 벤조산, 프로판산 등의 유기산과 모폴린, 피롤리딘, 피페리딘, 다이메틸아민, 다이에틸아민, N-메틸아닐린 등 이차 아민 유기염기를 조합하여 사용한다. 유기산은 0.01 당량의 촉매량으로부터 3 당량까지 사용 가능하며, 바람직하게는 0.1 내지 2 당량까지 사용한다. 유기염기는 0.01 당량의 촉매량으로부터 3 당량까지 사용 가능하며, 바람직하게는 0.2 내지 2 당량까지 사용한다. 반응 온도는 100~150 ℃의 범위에서 환류하며, 반응에서 나오는 부산물인 물을 제거하며 진행한다.Specific reaction conditions will be described in detail as follows. In this reaction, a solvent that does not participate in the reaction itself can be used, and aromatic hydrocarbons such as benzene, toluene, and xylene are preferably used. At this time, the solvent is refluxed while maintaining the reaction temperature at which water can be removed. As the additive, an organic acid such as acetic acid, benzoic acid or propanoic acid and a secondary amine organic base such as morpholine, pyrrolidine, piperidine, dimethylamine, diethylamine or N-methylaniline are used in combination. The organic acid may be used in an amount of from 0.01 equivalent to 3 equivalents, preferably from 0.1 to 2 equivalents. The organic base may be used in an amount of from 0.01 equivalent to 3 equivalents, preferably from 0.2 to 2 equivalents. The reaction temperature is refluxed in the range of 100 to 150 ° C and proceeds by removing the by-product water from the reaction.
본 발명에 따른 화학식 (2) 화합물의 제조를 위한 화학식 (14) 화합물은 상업적으로 구매하거나, 화학식 (16) 화합물로부터 당업계에 잘 알려진 일반적인 핵치환 반응에 의해 클로로아세토나이트릴과 반응시키는 것에 의해 간단히 얻을 수 있다. The compound of formula (14) for the preparation of the compound of formula (2) according to the present invention is commercially available or can be obtained by reacting the compound of formula (16) with chloroacetonitrile by a common nuclear displacement reaction well known in the art It can be obtained simply.
[화학식 16][Chemical Formula 16]
HS-AHS-A
상기 식에서 A는 위에서 정의된 바와 같다.Wherein A is as defined above.
한편, 화학식 (15)의 화합물은 공지의 화합물로서 상업적으로 구매하거나, 문헌의 방법에 따라 합성할 수 있다(Helv . Chim . Acta. 1999, 82, 326; Justus Liebigs Annalen der Chemie, 1950, 568 34).On the other hand, the compound of the formula (15) can be commercially obtained as a known compound or can be synthesized according to the literature method ( Helv . Chim . Acta ., 1999, 82 , 326, Justus Liebigs Annalen der Chemie , 1950, 568 34).
본 발명에 따른 신규 화학식 (2)의 알킬티오올레핀 유도체를 이용하는 방법에 의하면, 플루세토설푸론의 제조 중간체인 화학식 (1)의 화합물을 초저온 반응의 적용 없이 보다 훨씬 단순한 공정 단계를 통해 종래의 방법보다 높거나 동등 수준의 수율로 제조할 수 있다.According to the method using the alkylthiolefin derivative of the novel formula (2) according to the present invention, the compound of formula (1), which is a production intermediate of flutosulfuron, can be produced by a conventional method Can be produced at a higher or equivalent level of yield.
이하, 본 발명을 하기 제조예 및 실시예에 의거하여 보다 구체적으로 설명한다. 그러나, 이들 제조예 및 실시예는 본 발명에 대한 이해를 돕기 위한 것일 뿐, 어떤 의미로든 본 발명의 범위가 이들에 의해 한정되는 것은 아니다.Hereinafter, the present invention will be described more specifically based on the following Production Examples and Examples. However, these preparation examples and examples are only for the understanding of the present invention, and the scope of the present invention is not limited by them in any sense.
실시예Example 1: One: 화학식 (2) 화합물의 합성Synthesis of Compound (2)
실시예Example 1-1: 5-[메틸( 1-1: 5- [methyl ( 페닐Phenyl )아미노]-2-(프로판-2-) Amino] -2- (propane-2- 일설파닐Ylsulfanyl )펜타-2,4-) Penta-2,4- 다이엔나이트릴Dienonitrile
(이소프로필머캡토)아세토나이트릴(7.0 g, 60.8 mmol), 3-(N,N-메틸페닐)아미노아크롤레인(10.8 g, 66.9 mmol), N-메틸아닐린(9.8 g, 91.1 mmol) 및 벤조산(11.0 g, 90.0 mmol)을 톨루엔(100 mL)에 용해시킨 후, 16시간 환류시키면서 부산물인 물을 제거하였다. 더 이상 물이 나오지 않음이 확인되면 반응 온도를 상온까지 내린 후 물을 투입하여 층 분리를 실시하고, 유기층을 묽은 염산 수용액, 물의 순서대로 세척하고 감압증류를 실시하여 표제 화합물을 얻었다(12.6 g, 80% 수율).(10.8 g, 66.9 mmol), N-methylaniline (9.8 g, 91.1 mmol), and benzoic acid (6.8 g, 11.0 g, 90.0 mmol) was dissolved in toluene (100 mL), and the by-product water was removed by refluxing for 16 hours. After confirming that no more water was evacuated, the reaction temperature was lowered to room temperature, water was added thereto to effect layer separation, and the organic layer was washed with diluted hydrochloric acid aqueous solution and water in this order and distilled under reduced pressure to obtain the title compound (12.6 g, 80% yield).
1H NMR (CDCl3, 400 MHz) NMR H 1 (CDCl 3, 400 MHz)
이성질체 A. δ 7.36-7.05 (m, 7H), 5.91 (dd, J1 = 12.8 Hz, J2 = 11.6, 1H), 3.35-3.28 (m, 1H), 3.28 (s, 3H), 1.32 (d, J = 6.8 Hz, 6H)Isomer A. δ 7.36-7.05 (m, 7H) , 5.91 (dd, J 1 = 12.8 Hz, J 2 = 11.6, 1H), 3.35-3.28 (m, 1H), 3.28 (s, 3H), 1.32 (d , ≪ / RTI > J = 6.8 Hz, 6H)
이성질체 B. δ 7.36-7.05 (m, 7H), 5.76 (dd, J1 = 12.8 Hz, J2 = 11.6, 1H), 3.28 (s, 3H), 3.19-3.13 (m, 1H), 1.29 (d, J = 6.8 Hz, 6H)
Isomer B. δ 7.36-7.05 (m, 7H) , 5.76 (dd, J 1 = 12.8 Hz, J 2 = 11.6, 1H), 3.28 (s, 3H), 3.19-3.13 (m, 1H), 1.29 (d , ≪ / RTI > J = 6.8 Hz, 6H)
실시예Example 1-2: 5-( 1-2: 5- ( 모폴린Morpholine -4-일)-2-(프로판-2--4-yl) -2- (propane-2- 일설파닐Ylsulfanyl )펜타-2,4-) Penta-2,4- 다이엔나이트릴Dienonitrile
(이소프로필머캡토)아세토나이트릴(7.0 g, 60.8 mmol), 3-모폴리노아크롤레인(9.4 g, 66.9 mmol), 모폴린(7.9 g, 91.1 mmol) 및 아세트산(732 mg, 6.0 mmol)을 톨루엔(100 mL)에 용해시킨 후, 16시간 환류시키면서 부산물인 물을 제거하였다. 더 이상 물이 나오지 않음이 확인되면 반응 온도를 상온까지 내린 후 물을 투입하여 층 분리를 실시하고, 유기층을 묽은 염산 수용액, 물 순서대로 세척하고 감압증류를 실시하여 표제 화합물을 얻었다(11.2 g, 77 % 수율).(7.0 g, 60.8 mmol), 3-morpholino acrolein (9.4 g, 66.9 mmol), morpholine (7.9 g, 91.1 mmol) and acetic acid (732 mg, 6.0 mmol) After dissolving in toluene (100 mL), the by-product water was removed by refluxing for 16 hours. After confirming that no more water was evacuated, the reaction temperature was lowered to room temperature, water was added thereto to effect layer separation, and the organic layer was washed with diluted hydrochloric acid aqueous solution and water in order and distilled under reduced pressure to obtain the title compound (11.2 g, 77% yield).
1H NMR (CDCl3, 400 MHz)NMR H 1 (CDCl 3, 400 MHz)
이성질체 A. δ 6.98 (d, J = 12 Hz, 1H), 6.59 (d, J = 16 Hz, 1H), 5.55 (dd, J1 = 16, J2 = 12 Hz, 1H), 3.75~3.65 (m, 4H), 3.28~3.23 (m, 4H), 3.18 (m, 1H), 1.27 (d, J = 6.8 Hz, 6H)(Dd, J 1 = 16, J 2 = 12 Hz, 1H), 3.75-3.65 (d, J = m, 4H), 3.28-3.23 (m, 4H), 3.18 (m,
이성질체 B. δ 7.04 (d, J = 12 Hz, 1H), 6.60 (d, J = 12 Hz, 1H), 5.70 (dd, J1 = 12, J2 = 12 Hz, 1H), 3.75~3.65 (m, 4H), 3.28~3.23 (m, 4H), 3.16 (m, 1H), 1.30 (d, J = 6.8 Hz, 6H)
Isomer B. δ 7.04 (d, J = 12 Hz, 1H), 6.60 (d, J = 12 Hz, 1H), 5.70 (dd, J 1 = 12, J 2 = 12 Hz, 1H), 3.75 ~ 3.65 ( m, 4H), 3.28-3.23 (m, 4H), 3.16 (m,
실시예Example 1-3: 5-(피페리딘-1-일)-2-(프로판-2- 1-3: 5- (Piperidin-1-yl) -2- (propane-2- 일설파닐Ylsulfanyl )펜타-2,4-) Penta-2,4- 다이엔나이트릴Dienonitrile
(이소프로필머캡토)아세토나이트릴(7.0 g, 60.8 mmol), 3-피페리디노아크롤레인(9.3 g, 66.9 mmol), 피페리딘(7.8 g, 91.1 mmol) 및 아세트산(732 mg, 6.0 mmol)을 톨루엔(100 mL)에 용해시킨 후, 16시간 환류시키면서 부산물인 물을 제거하였다. 더 이상 물이 나오지 않음이 확인되면 반응 온도를 상온까지 내린 후 물을 투입하여 층 분리를 실시하고, 유기층을 묽은 염산 수용액, 물 순서대로 세척하고 감압증류를 실시하여 표제 화합물을 얻었다(9.3 g, 65% 수율).(7.8 g, 91.1 mmol) and acetic acid (732 mg, 6.0 mmol) in acetonitrile (7.0 g, 60.8 mmol), 3-piperidino acrolein (9.3 g, 66.9 mmol) Was dissolved in toluene (100 mL), and the by-product water was removed by refluxing for 16 hours. After confirming that no more water was evacuated, the reaction temperature was lowered to room temperature, water was added thereto to effect layer separation, and the organic layer was washed with a dilute hydrochloric acid aqueous solution and water in order and distilled under reduced pressure to obtain the title compound (9.3 g, 65% yield).
1H NMR (CDCl3 , 400 MHz) 1 H NMR (CDCl 3, 400 MHz)
이성질체 A. δ 6.98 (d, J = 12.0 Hz, 1H), 6.64 (d, J = 12.8 Hz, 1H), 5.50 (dd, J1 = 12.8, J2 = 12.0 Hz, 1Hz), 3.23 (br, 4H), 3.10 (m, 1H), 1.63 (br, 6H), 1.26 (d, J = 6.8 Hz, 6H)Isomer A. δ 6.98 (d, J = 12.0 Hz, 1H), 6.64 (d, J = 12.8 Hz, 1H), 5.50 (dd, J 1 = 12.8, J 2 = 12.0 Hz, 1Hz), 3.23 (br, 4H), 3.10 (m, IH), 1.63 (br, 6H), 1.26 (d, J = 6.8 Hz, 6H)
이성질체 B. δ 7.10 (d, J = 11.6 Hz, 1H), 6.65 (d, J = 12.8 Hz, 1H), 5.65 (dd, J1 = 12.8, J2 = 11.6 Hz, 1H), 3.23 (br, 4H), 3.10 (m, 1H), 1.63 (br, 6H), 1.29 (d, J = 6.8 Hz, 6H)
Isomer B. δ 7.10 (d, J = 11.6 Hz, 1H), 6.65 (d, J = 12.8 Hz, 1H), 5.65 (dd, J 1 = 12.8, J 2 = 11.6 Hz, 1H), 3.23 (br, 4H), 3.10 (m, IH), 1.63 (br, 6H), 1.29 (d, J = 6.8 Hz,
실시예Example 2: 2: 화학식 (1) 화합물의 합성Synthesis of Compound (1)
실시예Example 2-1: 2- 2-1: 2- 브로모Bromo -3--3- 이소프로필티오피리딘의Isopropylthiopyridine 합성(방법 A) Synthesis (Method A)
실시예 1-1에서 얻은 5-[메틸(페닐)아미노]-2-(프로판-2-일설파닐)펜타-2,4-다이엔나이트릴(14.9 g, 57.8 mmol)을 톨루엔(50 mL)과 에탄올(50 mL) 혼합 용매에 용해시킨 후, 브롬화수소 가스를 2시간 동안 상온에서 흘러주며 교반하였다. 반응이 완료되면 질소를 1시간 흘러주어 과량의 브롬화수소를 제거하였다. 반응 혼합물에 물(70 mL)을 투입하여 층 분리하고, 유기층을 20% 수산화나트륨 수용액과 물로 차례대로 세척한 후 감압증류를 실시하고, 실리카젤 컬럼 크로마토그래피로 정제하여 표제 화합물을 얻었다(10.7 g, 80% 수율).(14.9 g, 57.8 mmol) obtained in Example 1-1 was dissolved in toluene (50 mL), and the mixture was stirred at room temperature for 2 hours. ) And ethanol (50 mL), and then hydrogen bromide gas was stirred at room temperature for 2 hours. When the reaction was completed, excess hydrogen bromide was removed by flowing nitrogen for 1 hour. Water (70 mL) was added to the reaction mixture and the layers were separated. The organic layer was washed successively with 20% aqueous sodium hydroxide solution and water, and then subjected to vacuum distillation and purification by silica gel column chromatography to obtain the title compound (10.7 g , 80% yield).
1H NMR (CDCl3, δ): 8.16 (dd, J=2.0, 4.8 Hz, 1H), 7.58 (dd, J=2.0, 7.6 Hz, 1H), 7.23 (dd, J=4.8, 7.6 Hz, 1H), 3.50 (m, J=8.0 Hz, 1H), 1.38 (d, J=8.0 Hz, 6H)
1 H NMR (CDCl 3, δ ): 8.16 (dd, J = 2.0, 4.8 Hz, 1H), 7.58 (dd, J = 2.0, 7.6 Hz, 1H), 7.23 (dd, J = 4.8, 7.6 Hz, 1H ), 3.50 (m, J = 8.0 Hz, 1H), 1.38 (d, J = 8.0 Hz,
실시예Example 2-2: 2- 2-2: 2- 브로모Bromo -3--3- 이소프로필티오피리딘의Isopropylthiopyridine 합성(방법 B) Synthesis (Method B)
실시예 1-3에서 얻은 5-(피페리딘-1-일)-2-(프로판-2-일설파닐)펜타-2,4-다이엔나이트릴(13.7 g, 57.8 mmol)을 톨루엔(100 mL)에 용해시킨 후, 포화 브롬화수소/아세트산 용액(5 당량, 289 mmol)을 적가하여 교반하였다. 반응이 완결되면 반응 혼합물에 물(70 mL)를 투입하여 층 분리하였다. 유기층을 20% 수산화나트륨 수용액, 물 순서대로 세척하고 감압증류를 실시하여 실리카젤 컬럼 크로마토그래피로 정제하여 표제 화합물을 얻었다(10.0 g, 75% 수율).
(13.7 g, 57.8 mmol) obtained in Example 1-3 was dissolved in toluene (10 ml) and the mixture was stirred at room temperature for 2 hours. 100 mL), and a saturated solution of hydrogen bromide / acetic acid (5 eq, 289 mmol) was added dropwise and stirred. When the reaction was completed, water (70 mL) was added to the reaction mixture to separate the layers. The organic layer was washed with 20% aqueous sodium hydroxide solution and water in order, and the residue was purified by silica gel column chromatography using reduced pressure distillation to obtain the title compound (10.0 g, 75% yield).
실시예Example 2-3: 2- 2-3: 2- 브로모Bromo -3--3- 이소프로필티오피리딘의Isopropylthiopyridine 합성(방법 C) Synthesis (Method C)
(이소프로필머캡토)아세토나이트릴(7.0 g, 60.8 mmol), 3-(N,N-메틸페닐)아미노아크롤레인(10.8 g, 66.9 mmol), 피페리딘(7.8 g, 91.1 mmol) 및 아세트산(360 mg, 6.0 mmol)을 톨루엔 (100 mL)에 용해시킨 후 16시간 환류시키면서 부산물인 물을 제거하였다. 더 이상 물이 나오지 않아 반응이 완료되면 반응 온도를 상온까지 냉각시킨 후 특별한 정제과정 없이, 브롬화수소/아세트산 용액(70.8 g, 289 mmol)에 그대로 적가하였다. 2시간 동안 상온에서 교반한 후 반응 혼합물에 물(70 mL)를 투입하여 층 분리하였다. 유기층을 20% 수산화나트륨 수용액, 물 순서대로 세척하고 유기층을 진공 증류하여 표제 화합물을 얻었다(9.9 g, 70% 수율).
(10.8 g, 66.9 mmol), piperidine (7.8 g, 91.1 mmol), and acetic acid (360 mL) were added to a solution of 3- (N, N-methylphenyl) amino acrolein mg, 6.0 mmol) was dissolved in toluene (100 mL) and refluxed for 16 hours to remove water as a by-product. After the reaction was completed, the reaction temperature was cooled to room temperature, and the solution was directly added to the hydrogen bromide / acetic acid solution (70.8 g, 289 mmol) without any special purification. After stirring at room temperature for 2 hours, water (70 mL) was added to the reaction mixture to separate layers. The organic layer was washed with 20% aqueous sodium hydroxide solution and water, and the organic layer was vacuum distilled to obtain the title compound (9.9 g, 70% yield).
이상에서 살펴본 바와 같이, 본 발명에 따른 화학식(2)의 신규 알킬티오올레핀 유도체 화합물을 이용하는 방법에 의하면, 종래의 방법과 비교하여 훨씬 단순한 공정 단계를 통해 화학식 (1)의 화합물을 종래의 방법보다 높거나 동등 수준의 수율로 제조할 수 있다.As described above, according to the method using the novel alkylthiolefin derivative compound of formula (2) according to the present invention, the compound of formula (1) can be obtained by a simpler process step than the conventional method Can be produced at a high or equivalent level of yield.
Claims (12)
[화학식 2]
상기 식에서,
A는 C3-C5-알킬 또는 C3-C6사이클로알킬을 나타내거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 벤질을 나타내고,
X는 사이클릭 이차 아민 또는 R1R2N의 이차 아민을 나타내며, 이때 R1 및 R2는 각각 독립적으로 C1~C3 알킬이거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 페닐을 나타낸다. An alkylthiolefin derivative compound of formula (2) for use in the manufacture of flutosulfuron.
(2)
In this formula,
A is C 3 -C 5 - alkyl or C 3 -C 6, or represent cycloalkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - by a substituent selected from alkoxy of 1 to 5, a substituted or unsubstituted benzyl Lt; / RTI >
X represents a secondary amine or cyclic secondary amine R 1 R 2 N, wherein R 1 and R 2 are each independently a C 1 ~ C 3 alkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - ≪ / RTI > alkoxy, < RTI ID = 0.0 > and / or < / RTI >
[화학식 2]
[화학식 14]
[화학식 15]
상기 식에서, A는 C3-C5-알킬 또는 C3-C6사이클로알킬을 나타내거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 벤질을 나타내고,
X는 사이클릭 이차 아민 또는 R1R2N의 이차 아민을 나타내며, 이때 R1 및 R2는 각각 독립적으로 C1~C3 알킬이거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 페닐을 나타낸다. A process for producing an alkylthiolefin derivative compound of formula (2), wherein the compound of formula (14) and the compound of formula (15) are simultaneously reacted with an organic acid and an organic base in a solvent.
(2)
[Chemical Formula 14]
[Chemical Formula 15]
Wherein, A is C 3 -C 5 - alkyl or C 3 -C 6, or represent cycloalkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - 1 to 5 is substituted by a substituent selected from alkoxy or beach Benzyl,
X represents a secondary amine or cyclic secondary amine R 1 R 2 N, wherein R 1 and R 2 are each independently a C 1 ~ C 3 alkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - ≪ / RTI > alkoxy, < RTI ID = 0.0 > and / or < / RTI >
[화학식 1]
[화학식 2]
상기 식에서,
A는 C3-C5-알킬 또는 C3-C6사이클로알킬을 나타내거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 벤질을 나타내고,
X는 사이클릭 이차 아민 또는 R1R2N의 이차 아민을 나타내며, 이때 R1 및 R2는 각각 독립적으로 C1~C3 알킬이거나, C1-C2-알킬 및 C1-C2-알콕시로부터 선택된 치환체에 의해 1 내지 5 치환되거나 비치환된 페닐을 나타낸다.A process for preparing a pyridine derivative compound represented by the following formula (1) for use in the production of flutosulfuron, which comprises reacting a compound represented by the formula (2) below with hydrogen bromide in a solvent.
[Chemical Formula 1]
(2)
In this formula,
A is C 3 -C 5 - alkyl or C 3 -C 6, or represent cycloalkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - by a substituent selected from alkoxy of 1 to 5, a substituted or unsubstituted benzyl Lt; / RTI >
X represents a secondary amine or cyclic secondary amine R 1 R 2 N, wherein R 1 and R 2 are each independently a C 1 ~ C 3 alkyl, C 1 -C 2 - alkyl, and C 1 -C 2 - ≪ / RTI > alkoxy, < RTI ID = 0.0 > and / or < / RTI >
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