JP2004217619A - Method for producing cycloalkanone derivative - Google Patents
Method for producing cycloalkanone derivative Download PDFInfo
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- JP2004217619A JP2004217619A JP2003379321A JP2003379321A JP2004217619A JP 2004217619 A JP2004217619 A JP 2004217619A JP 2003379321 A JP2003379321 A JP 2003379321A JP 2003379321 A JP2003379321 A JP 2003379321A JP 2004217619 A JP2004217619 A JP 2004217619A
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- 238000004519 manufacturing process Methods 0.000 title claims abstract description 29
- 150000001875 compounds Chemical class 0.000 claims abstract description 62
- 150000001299 aldehydes Chemical class 0.000 claims abstract description 45
- 239000003054 catalyst Substances 0.000 claims abstract description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 16
- 238000000034 method Methods 0.000 claims abstract description 15
- 238000005882 aldol condensation reaction Methods 0.000 claims abstract description 13
- 239000002253 acid Substances 0.000 claims description 18
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 6
- 238000006297 dehydration reaction Methods 0.000 claims description 5
- 238000000926 separation method Methods 0.000 claims description 5
- 125000003118 aryl group Chemical group 0.000 claims description 4
- 230000003647 oxidation Effects 0.000 claims description 4
- 238000007254 oxidation reaction Methods 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000001257 hydrogen Substances 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 3
- 125000001118 alkylidene group Chemical group 0.000 claims description 2
- 125000000732 arylene group Chemical group 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 230000007935 neutral effect Effects 0.000 claims description 2
- 150000001735 carboxylic acids Chemical class 0.000 claims 2
- 150000005690 diesters Chemical class 0.000 claims 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims 1
- 238000010979 pH adjustment Methods 0.000 claims 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 abstract description 20
- 239000000463 material Substances 0.000 abstract description 7
- 239000013543 active substance Substances 0.000 abstract description 6
- 150000001924 cycloalkanes Chemical class 0.000 abstract 1
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 48
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclopentanone Chemical compound O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 44
- 238000006243 chemical reaction Methods 0.000 description 42
- 239000010410 layer Substances 0.000 description 38
- 239000000203 mixture Substances 0.000 description 30
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 24
- HGBOYTHUEUWSSQ-UHFFFAOYSA-N pentanal Chemical compound CCCCC=O HGBOYTHUEUWSSQ-UHFFFAOYSA-N 0.000 description 21
- -1 alkyl aldehyde Chemical class 0.000 description 18
- 239000002585 base Substances 0.000 description 17
- 239000000047 product Substances 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 15
- DYVAUIYAEICDNS-UHFFFAOYSA-N 2-(1-hydroxypentyl)cyclopentan-1-one Chemical compound CCCCC(O)C1CCCC1=O DYVAUIYAEICDNS-UHFFFAOYSA-N 0.000 description 13
- YZKUNNFZLUCEET-RMKNXTFCSA-N (2e)-2-pentylidenecyclopentan-1-one Chemical compound CCCC\C=C1/CCCC1=O YZKUNNFZLUCEET-RMKNXTFCSA-N 0.000 description 12
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 12
- 239000002994 raw material Substances 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 9
- 238000001816 cooling Methods 0.000 description 8
- 238000004821 distillation Methods 0.000 description 8
- 239000001488 sodium phosphate Substances 0.000 description 6
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 6
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 6
- 235000019801 trisodium phosphate Nutrition 0.000 description 6
- 239000003205 fragrance Substances 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 238000004448 titration Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 230000032683 aging Effects 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 239000000539 dimer Substances 0.000 description 4
- 230000007613 environmental effect Effects 0.000 description 4
- MEKOFIRRDATTAG-UHFFFAOYSA-N 2,2,5,8-tetramethyl-3,4-dihydrochromen-6-ol Chemical compound C1CC(C)(C)OC2=C1C(C)=C(O)C=C2C MEKOFIRRDATTAG-UHFFFAOYSA-N 0.000 description 3
- ILHZVKAXFCDFMT-UHFFFAOYSA-N 2-pentylcyclopent-2-en-1-one Chemical compound CCCCCC1=CCCC1=O ILHZVKAXFCDFMT-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- 150000001340 alkali metals Chemical class 0.000 description 3
- BGTOWKSIORTVQH-HOSYLAQJSA-N cyclopentanone Chemical class O=[13C]1CCCC1 BGTOWKSIORTVQH-HOSYLAQJSA-N 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 239000000796 flavoring agent Substances 0.000 description 3
- 235000019634 flavors Nutrition 0.000 description 3
- 238000006317 isomerization reaction Methods 0.000 description 3
- KVWWIYGFBYDJQC-UHFFFAOYSA-N methyl dihydrojasmonate Chemical compound CCCCCC1C(CC(=O)OC)CCC1=O KVWWIYGFBYDJQC-UHFFFAOYSA-N 0.000 description 3
- 235000006408 oxalic acid Nutrition 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- ITQTTZVARXURQS-UHFFFAOYSA-N 3-methylpyridine Chemical compound CC1=CC=CN=C1 ITQTTZVARXURQS-UHFFFAOYSA-N 0.000 description 2
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexanone Chemical compound O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 2
- DIOQZVSQGTUSAI-UHFFFAOYSA-N decane Chemical compound CCCCCCCCCC DIOQZVSQGTUSAI-UHFFFAOYSA-N 0.000 description 2
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 239000011261 inert gas Substances 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- BKIMMITUMNQMOS-UHFFFAOYSA-N nonane Chemical compound CCCCCCCCC BKIMMITUMNQMOS-UHFFFAOYSA-N 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- RSJKGSCJYJTIGS-UHFFFAOYSA-N undecane Chemical compound CCCCCCCCCCC RSJKGSCJYJTIGS-UHFFFAOYSA-N 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 1
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- 238000006220 Baeyer-Villiger oxidation reaction Methods 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 1
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 1
- 150000001342 alkaline earth metals Chemical class 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000011260 aqueous acid Substances 0.000 description 1
- 229910052786 argon Inorganic materials 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229940088623 biologically active substance Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 229910052791 calcium Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- XXJWXESWEXIICW-UHFFFAOYSA-N diethylene glycol monoethyl ether Chemical compound CCOCCOCCO XXJWXESWEXIICW-UHFFFAOYSA-N 0.000 description 1
- 229940075557 diethylene glycol monoethyl ether Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- NCWQJOGVLLNWEO-UHFFFAOYSA-N methylsilicon Chemical compound [Si]C NCWQJOGVLLNWEO-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000007800 oxidant agent Substances 0.000 description 1
- 230000001590 oxidative effect Effects 0.000 description 1
- 239000002798 polar solvent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
Landscapes
- Pyrane Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
Description
本発明は、生理活性物質や香料の合成中間体として有用な２−（１−ヒドロキシアルキル）シクロアルカノン及び／又は２−（１−ヒドロキシアリール）シクロアルカノンの製造法、並びにそれを用いた、香料素材や生理活性物質として有用なアルキル（３−オキソ−２−アルキルシクロアルキル）アセテート及び／又はアルキル（３−オキソ−２−アリールシクロアルキル）アセテート、並びに５−アルキル−５−アルカノリド及び／又は５−アリール−５−アルカノリドの製造法に関する。 The present invention relates to a method for producing 2- (1-hydroxyalkyl) cycloalkanone and / or 2- (1-hydroxyaryl) cycloalkanone, which is useful as an intermediate for synthesizing a physiologically active substance or a flavor, and using the same. Alkyl (3-oxo-2-alkylcycloalkyl) acetate and / or alkyl (3-oxo-2-arylcycloalkyl) acetate useful as a fragrance material or a physiologically active substance, and 5-alkyl-5-alkanolides and / or Or a method for producing a 5-aryl-5-alkanolide.
２−（１−ヒドロキシアルキル）シクロアルカノンの製造法として、特許文献１には、シクロアルカノンとアルキルアルデヒドとを、アルキルアルデヒド１モルに対して、塩基触媒を約０．０５〜０．１モル用いてアルドール縮合する方法が、また、特許文献２には、アルキルアルデヒド１モルに対して、塩基触媒を０．０４モル以下用いてアルドール縮合する方法が記載されている。 As a method for producing 2- (1-hydroxyalkyl) cycloalkanone, Patent Literature 1 discloses that a cycloalkanone and an alkyl aldehyde are used in an amount of about 0.05 to 0.1 with a base catalyst per mole of alkyl aldehyde. A method of performing aldol condensation using a mole, and Patent Document 2 describes a method of performing aldol condensation using a base catalyst in an amount of 0.04 mol or less with respect to 1 mol of an alkyl aldehyde.
しかしながら、アルキルアルデヒドは容易に酸化してアルキルカルボン酸となる性質があり、このアルキルカルボン酸がアルドール縮合中に塩基触媒と反応し、活性を大きく低下させるため、収率及び選択率の低下を招くことが多い。このような酸化を防ぐため、アルキルアルデヒドを窒素シール等で貯蔵、使用する方法が取られるが、酸化は少しずつ進行するため、アルキルカルボン酸の混入は避けられない。 However, alkyl aldehydes have the property of easily oxidizing to alkyl carboxylic acids, and this alkyl carboxylic acid reacts with a base catalyst during aldol condensation and greatly reduces the activity, which leads to a decrease in yield and selectivity. Often. In order to prevent such oxidation, a method of storing and using an alkyl aldehyde with a nitrogen seal or the like is used. However, since the oxidation progresses little by little, mixing of an alkyl carboxylic acid is inevitable.
また、特許文献１及び２に記載の方法では、アルキルアルデヒドに対してシクロアルカノンを過剰に使用するため、反応後に未反応のシクロアルカノンが残存する。反応に使用する水層部はシクロアルカノンを多量に溶解するため、一回の反応で廃棄すると未反応で残存しているシクロアルカノンを大量に損失することになり、環境負荷が増大する。
本発明の課題は、アルデヒド中のカルボン酸含有量に関わらず、安定して高収率、高選択率で２−（１−ヒドロキシアルキル）シクロアルカノン及び／又は２−（１−ヒドロキシアリール）シクロアルカノンを製造し、さらに、シクロアルカノンを効率的に使用して、環境負荷を低減することのできる２−（１−ヒドロキシアルキル）シクロアルカノン及び／又は２−（１−ヒドロキシアリール）シクロアルカノンの製造法、並びにそれを用いた香料素材や生理活性物質として有用なシクロアルカノン誘導体の製造法を提供することにある。 An object of the present invention is to stably provide 2- (1-hydroxyalkyl) cycloalkanone and / or 2- (1-hydroxyaryl) with high yield and high selectivity regardless of the carboxylic acid content in the aldehyde. 2- (1-hydroxyalkyl) cycloalkanone and / or 2- (1-hydroxyaryl) capable of producing cycloalkanone and reducing the environmental load by using cycloalkanone efficiently An object of the present invention is to provide a method for producing a cycloalkanone, and a method for producing a cycloalkanone derivative which is useful as a flavor material or a physiologically active substance using the same.
本発明者らは、塩基触媒の添加量を、アルデヒドに含まれるカルボン酸と等モル以上で、かつアルデヒドに対し特定量以下に制御して反応を行うことにより、アルデヒドのカルボン酸含有量に関わらず、安定して高収率、高選択率で２−（１−ヒドロキシアルキル）シクロアルカノン及び／又は２−（１−ヒドロキシアリール）シクロアルカノンが得られることを見いだした。 The present inventors control the amount of the base catalyst to be added in an amount equal to or greater than the molar amount of the carboxylic acid contained in the aldehyde and to a specific amount or less with respect to the aldehyde, thereby effecting the reaction regardless of the carboxylic acid content of the aldehyde. It has been found that 2- (1-hydroxyalkyl) cycloalkanone and / or 2- (1-hydroxyaryl) cycloalkanone can be obtained stably with high yield and high selectivity.
さらに、反応に使用する水層部を繰り返し再使用することにより、シクロアルカノンを効率的に使用でき、かつ排水を低減し環境負荷低減につながることを見いだした。その中で、酸によるｐＨ調整及び分層後の水層部を再使用する場合、多量の中和塩が蓄積すると反応収率が低下するものの、一回の反応で使用する塩基触媒量を反応が進行する最低限に抑えることによって、その低下を抑えることが可能であることを見いだした。 Furthermore, it has been found that by repeatedly reusing the aqueous layer used for the reaction, cycloalkanone can be used efficiently and the wastewater is reduced, leading to a reduction in the environmental burden. In the case of reusing the aqueous layer after adjusting the pH with an acid and separating the aqueous layer, the reaction yield decreases when a large amount of neutralized salt accumulates, but the amount of the base catalyst used in one reaction is reduced. It has been found that it is possible to suppress the decline by minimizing the progression.
本発明は、シクロアルカノンと、式（２）で表されるアルデヒド（以下アルデヒド（２）という）とを、水及び塩基触媒存在下でアルドール縮合して、式（３）で表される２−（１−ヒドロキシアルキル）シクロアルカノン及び／又は２−（１−ヒドロキシアリール）シクロアルカノン（以下化合物（３）という）を製造する方法であって、塩基触媒の添加量（単位モル；以下Ａという）が、アルデヒド（２）中に含まれる式（１）で表されるカルボン酸（以下カルボン酸（１）という）の量（単位モル；以下Ｂという）以上で、かつＡとＢの差（Ａ−Ｂ）がアルデヒド（２）１モルに対し０．０６モル以下である、化合物（３）の製造法、及びこのアルドール縮合反応後に得られる水層部を再使用する、化合物（３）の製造法を提供する。 The present invention provides an aldol condensation of a cycloalkanone and an aldehyde represented by the formula (2) (hereinafter referred to as aldehyde (2)) in the presence of water and a base catalyst to obtain a compound represented by the formula (3) A method for producing-(1-hydroxyalkyl) cycloalkanone and / or 2- (1-hydroxyaryl) cycloalkanone (hereinafter referred to as compound (3)), wherein the amount of base catalyst added (unit mol; A) is not less than the amount (unit mol; hereinafter referred to as B) of the carboxylic acid represented by the formula (1) (hereinafter referred to as carboxylic acid (1)) contained in the aldehyde (2), and The method for producing the compound (3), wherein the difference (AB) is 0.06 mol or less per 1 mol of the aldehyde (2), and the compound (3) wherein the aqueous layer obtained after the aldol condensation reaction is reused. ) Is provided.
（式中、ｎは１又は２の整数、Ｒ1は水素原子又は炭素数１〜８の直鎖もしくは分岐鎖のアルキル基、あるいは置換もしくは無置換のアリール基を示す。）
本発明は、また、上記製造法で得られた化合物（３）を脱水反応させて、式（４）
(In the formula, n represents an integer of 1 or 2, and R 1 represents a hydrogen atom, a linear or branched alkyl group having 1 to 8 carbon atoms, or a substituted or unsubstituted aryl group.)
The present invention also provides a compound (3) obtained by the above production method, wherein the compound (3) is subjected to a dehydration reaction to obtain a compound of the formula (4)
（式中、ｎ及びＲ1は前記の意味を有する。）
で表される２−（アルキリデン）シクロアルカノン及び／又は２−（アリーレン）シクロアルカノン（以下化合物（４）という）を得、次いで異性化反応させて、式（５）
(In the formula, n and R 1 have the above-mentioned meanings.)
2- (alkylidene) cycloalkanone and / or 2- (arylene) cycloalkanone (hereinafter referred to as compound (4)) represented by the formula
（式中、ｎ及びＲ1は前記の意味を有する。）
で表される２−（アルキル）シクロアルケノン及び／又は２−（アリール）シクロアルケノン（以下化合物（５）という）とし、次いで式（６）
(In the formula, n and R 1 have the above-mentioned meanings.)
2- (alkyl) cycloalkenones and / or 2- (aryl) cycloalkenones (hereinafter referred to as compound (5)) represented by the following formula:
（式中、Ｒ2は炭素数１〜３の直鎖又は分岐鎖のアルキル基を示し、２個のＲ2は同一でも異なっていてもよい。）
で表されるマロン酸ジエステル（以下化合物（６）という）と反応させ、次いで水を反応させる、式（７）
(In the formula, R 2 represents a linear or branched alkyl group having 1 to 3 carbon atoms, and the two R 2 may be the same or different.)
Reacting with a malonic acid diester represented by the following formula (hereinafter referred to as compound (6)) and then reacting with water:
（式中、ｎ、Ｒ1及びＲ2は前記の意味を有する。）
で表されるアルキル（３−オキソ−２−アルキルシクロアルキル）アセテート及び／又はアルキル（３−オキソ−２−アリールシクロアルキル）アセテート（以下化合物（７）という）の製造法、並びに化合物（３）を脱水反応させて、化合物（４）を得、次いで異性化反応させて、化合物（５）とし、次いで水素還元させた後、バイヤービリガー酸化させる、式（８）で表される５−アルキル−５−アルカノリド及び／又は５−アリール−５−アルカノリド（以下化合物（８）という）の製造法を提供する。
(In the formula, n, R 1 and R 2 have the above-mentioned meanings.)
Production method of alkyl (3-oxo-2-alkylcycloalkyl) acetate and / or alkyl (3-oxo-2-arylcycloalkyl) acetate (hereinafter, referred to as compound (7)) represented by the formula: and compound (3) Is subjected to a dehydration reaction to obtain a compound (4), which is then subjected to isomerization reaction to obtain a compound (5), which is then reduced with hydrogen and then subjected to Bayer-Villiger oxidation, which is represented by the formula (8). Provided is a method for producing a 5-alkanolide and / or 5-aryl-5-alkanolide (hereinafter, referred to as compound (8)).
（式中、ｎ及びＲ1は前記の意味を示す。） (In the formula, n and R 1 have the same meanings as described above.)
本発明の方法によれば、シクロアルカノンと、アルデヒド（２）を原料として、アルデヒド（２）中に含まれるカルボン酸（１）の含有量に関わらず、安定して高収率、高選択率で化合物（３）を製造するとともに、シクロアルカノンを効率的に使用でき、排水の低減により環境負荷を低減することができる。更に、得られた化合物（３）を用い、香料素材や生理活性物質として有用な化合物（７）及び化合物（８）を効率的に製造することができる。 ADVANTAGE OF THE INVENTION According to the method of this invention, a cycloalkanone and an aldehyde (2) are raw materials, and a high yield and a high selection are obtained stably irrespective of the content of the carboxylic acid (1) contained in an aldehyde (2). The compound (3) can be produced at a high rate, the cycloalkanone can be used efficiently, and the environmental load can be reduced by reducing the wastewater. Furthermore, the compound (7) and the compound (8) useful as a fragrance | flavor material and a biologically active substance can be efficiently manufactured using the obtained compound (3).
［化合物（３）の製造法］
本発明の化合物（３）の製造法に用いられるシクロアルカノンは、シクロペンタノン又はシクロヘキサノンであり、シクロペンタノンが好ましい。また、アルデヒド（２）としては、Ｒ1が炭素数１〜８のアルキル基であるものが好ましく、炭素数３〜５のアルキルアルデヒドが更に好ましく、炭素数４の直鎖アルキル基を有するアルデヒド（バレルアルデヒド）が特に好ましい。
[Method for producing compound (3)]
The cycloalkanone used in the method for producing the compound (3) of the present invention is cyclopentanone or cyclohexanone, and cyclopentanone is preferable. As the aldehyde (2), R 1 is preferably an alkyl group having 1 to 8 carbon atoms, more preferably an alkyl aldehyde having 3 to 5 carbon atoms, and an aldehyde having a linear alkyl group having 4 carbon atoms ( Valeraldehyde) is particularly preferred.
本発明に用いられるアルデヒド（２）中には、その酸化物であるカルボン酸（１）が含まれている。アルデヒド（２）中のカルボン酸（１）の定量法としては、例えば液体クロマトグラフィー、ガスクロマトグラフィー、滴定等が挙げられるが、簡便性を考慮すると滴定によって求められる酸価を利用するのが望ましい。 The aldehyde (2) used in the present invention contains a carboxylic acid (1) as an oxide thereof. As a method for quantifying the carboxylic acid (1) in the aldehyde (2), for example, liquid chromatography, gas chromatography, titration and the like can be mentioned. In view of simplicity, it is desirable to use the acid value obtained by titration. .
本発明に用いられる塩基触媒としては、式（９）で表される化合物が好ましい。 As the base catalyst used in the present invention, a compound represented by the formula (9) is preferable.
Ｍ(ＯＨ)m （９）
（式中、Ｍは、Ｌｉ、Ｎａ、Ｋ等のアルカリ金属、又はＭｇ、Ｃａ、Ｂａ等のアルカリ土類金属であり、好ましくはアルカリ金属である。ｍは１又は２の整数である。）
本発明において、塩基触媒の添加量（Ａ）は、良好な反応速度や収率を得る観点から、アルデヒド（２）中に含まれるカルボン酸（１）の量（Ｂ）以上、即ち等モル以上で、かつＡとＢの差（Ａ−Ｂ）がアルデヒド（２）１モルに対し０．０６モル以下、好ましくは０〜０．０２モル、更に好ましくは０．００１〜０．００５モルである。
M (OH) m (9)
(In the formula, M is an alkali metal such as Li, Na, or K, or an alkaline earth metal such as Mg, Ca, or Ba, and is preferably an alkali metal. M is an integer of 1 or 2.)
In the present invention, the addition amount (A) of the base catalyst is equal to or more than the amount (B) of the carboxylic acid (1) contained in the aldehyde (2), that is, equal to or more from the viewpoint of obtaining a favorable reaction rate and yield. And the difference (AB) between A and B is 0.06 mol or less, preferably 0 to 0.02 mol, more preferably 0.001 to 0.005 mol, per 1 mol of the aldehyde (2). .
アルデヒド（２）中に含まれるカルボン酸（１）の量（Ｂ）は、アルデヒド（２）の酸価（ｍｇ−ＫＯＨ／ｇ）のＫＯＨ量のモル数に相当する。つまり、アルデヒド（２）の酸価（ｍｇ−ＫＯＨ／ｇ）とアルデヒド（２）の量からＫＯＨ必要モル数を求め、それと等モル量以上の塩基触媒を添加することにより、収率や選択率の低下を抑えることができる。また、ＡとＢの差（Ａ−Ｂ）は、塩基触媒の添加量（Ａ）から、カルボン酸（１）と反応する塩基触媒の量（Ｂに相当する）を差し引いた、反応を進行させるための有効塩基触媒量であり、この（Ａ−Ｂ）を、アルデヒド（２）１モルに対し０．０６モル以下とすることにより、シクロアルカノンダイマー等の副生物の生成を抑えることができる。更に水層部を繰り返し再使用しても高い収率を維持できる。 The amount (B) of the carboxylic acid (1) contained in the aldehyde (2) corresponds to the number of moles of the KOH amount in the acid value (mg-KOH / g) of the aldehyde (2). That is, the required number of moles of KOH is determined from the acid value (mg-KOH / g) of the aldehyde (2) and the amount of the aldehyde (2), and the yield or selectivity is obtained by adding a base catalyst in an amount equal to or more than that. Can be suppressed. The difference (A-B) between A and B is obtained by subtracting the amount of the base catalyst that reacts with the carboxylic acid (1) (corresponding to B) from the amount of the base catalyst added (A), thereby allowing the reaction to proceed. The amount of (AB) is 0.06 mol or less based on 1 mol of aldehyde (2), whereby the production of by-products such as cycloalkanone dimer can be suppressed. . Further, a high yield can be maintained even when the aqueous layer is repeatedly reused.
また、本発明の製造法において、水の添加量は、アルデヒド（２）のダイマー、シクロアルカノンのダイマー、高沸成分等の副生成物を抑える観点から、シクロアルカノンに対し０．２〜１．２重量倍が好ましく、０．４〜１．２重量倍が更に好ましく、０．４〜０．６重量倍が特に好ましい。 Further, in the production method of the present invention, the amount of water to be added is 0.2 to 0.2 parts by weight of cycloalkanone from the viewpoint of suppressing dimers of aldehyde (2), dimers of cycloalkanone, and high-boiling components. It is preferably 1.2 times by weight, more preferably 0.4 to 1.2 times by weight, and particularly preferably 0.4 to 0.6 times by weight.
シクロアルカノンとアルデヒド（２）とは、良好な収率を得る観点から、アルデヒド（２）１モルに対し、シクロアルカノンを１モル以上反応させることが好ましく、過剰分のシクロアルカノン回収等の生産性を考慮すると１．２〜４．０モルが好ましく、１．２〜３．０モルがより好ましく、１．５〜２．７モルが更に好ましい。 From the viewpoint of obtaining a good yield, the cycloalkanone and the aldehyde (2) are preferably reacted with 1 mol or more of the cycloalkanone per 1 mol of the aldehyde (2). In consideration of the productivity of the compound, 1.2 to 4.0 mol is preferable, 1.2 to 3.0 mol is more preferable, and 1.5 to 2.7 mol is further preferable.
アルドール縮合の反応温度は、水層部が凝固するのを防止し、シクロアルカノンの２量体等の生成を抑える観点から、−５〜４０℃が好ましく、−５〜３０℃が更に好ましい。 The reaction temperature of the aldol condensation is preferably from -5 to 40 ° C, more preferably from -5 to 30 ° C, from the viewpoint of preventing the aqueous layer from solidifying and suppressing the formation of cycloalkanone dimer and the like.
本発明の製造法は、シクロアルカノン、水及び塩基触媒を反応槽に仕込み、前記の反応温度に制御しながら、アルデヒド（２）を滴下するのが望ましい。滴下時間は反応槽の温度制御能力に応じて変化させればよく収率に影響しない。滴下終了後、転化率を高めるため必要に応じて熟成反応を行ってもよい。熟成時間も特に限定されないが、長くなると少しずつ副生成物が増加していく。生産性を考慮すると、アルデヒド（２）の滴下時間は１〜８時間程度、熟成時間は１〜６時間程度が望ましい。また、この反応は、不活性ガス雰囲気下で行うのが好ましい。不活性ガスとしては、窒素、アルゴン等が挙げられる。 In the production method of the present invention, it is desirable that cycloalkanone, water and a base catalyst are charged into a reaction vessel, and the aldehyde (2) is added dropwise while controlling the reaction temperature. The dropping time may be changed according to the temperature control capability of the reaction tank, and does not affect the yield. After the completion of the dropwise addition, an aging reaction may be performed as needed to increase the conversion. The aging time is not particularly limited, but the by-product gradually increases as the aging time increases. In consideration of productivity, the dropping time of the aldehyde (2) is preferably about 1 to 8 hours, and the aging time is preferably about 1 to 6 hours. This reaction is preferably performed in an inert gas atmosphere. Examples of the inert gas include nitrogen, argon, and the like.
アルドール縮合反応の圧力は、絶対圧で１０ｋＰａ〜１ＭＰａが好ましく、５０〜３００ｋＰａが更に好ましく、１００ｋＰａ前後が特に好ましい。 The pressure of the aldol condensation reaction is preferably 10 kPa to 1 MPa in absolute pressure, more preferably 50 to 300 kPa, and particularly preferably about 100 kPa.
アルドール縮合反応は、シクロアルカノンと水の２層系の反応であるから、これを破壊するような溶媒を用いるのは好ましくない。本発明で用いられる溶媒は、反応系において不活性で、生成物の分離精製を阻害しないものであれば特に制限されず、例えば、沸点範囲が１４０〜２１０℃程度の、芳香族炭化水素系溶媒（ベンゼン、トルエン等）、脂肪族炭化水素系溶媒（ノナン、デカン、ウンデカン等）等が挙げられる。 Since the aldol condensation reaction is a two-layer system reaction of cycloalkanone and water, it is not preferable to use a solvent that destroys this. The solvent used in the present invention is not particularly limited as long as it is inert in the reaction system and does not inhibit the separation and purification of the product. For example, an aromatic hydrocarbon solvent having a boiling range of about 140 to 210 ° C. (Benzene, toluene, etc.) and aliphatic hydrocarbon solvents (nonane, decane, undecane, etc.).
アルドール縮合反応で使用した水層部はシクロアルカノンを多量に含むため、分層して水層部を繰り返し再使用することが望ましい。油層部に水層部のいくらかが分配するため、再使用して反応を行う際はその量の水や塩基触媒を追加してもよい。必要なら、さらに追加してもよい。 Since the aqueous layer used in the aldol condensation reaction contains a large amount of cycloalkanone, it is desirable to separate the aqueous layer and repeatedly reuse the aqueous layer. Since some of the water layer is distributed to the oil layer, the same amount of water or a base catalyst may be added when the reaction is performed after reuse. If necessary, more may be added.
塩基触媒の存在下では、分層に時間を要することがある。この場合は、酸の添加によって分層しやすいｐＨまで調整し、分層して再使用することも可能である。分層後の油層部からもシクロアルカノンを蒸留回収する必要がある場合は、化合物（３）の分解を抑えるため、酸性側、好ましくはｐＨを４〜７に調整するのが望ましい。 In the presence of a base catalyst, time may be required for separation. In this case, it is also possible to adjust the pH to a value that facilitates layer separation by adding an acid, separate the layer, and reuse the layer. If it is necessary to recover cycloalkanone by distillation from the oil layer after the separation, it is desirable to adjust the acid side, preferably the pH to 4 to 7, in order to suppress the decomposition of compound (3).
ここで用いられる酸は特に制限されず、一般的な有機酸、無機酸が使用できるが、取り扱いやすさ、価格等の面から、硫酸、リン酸、縮合リン酸が望ましい。 The acid used here is not particularly limited, and general organic acids and inorganic acids can be used. However, sulfuric acid, phosphoric acid, and condensed phosphoric acid are desirable from the viewpoint of ease of handling and cost.
酸を添加した場合は、水層部を再使用して反応を行う際に、前記の塩基触媒量に加え、水層部を中性からアルカリ側（ｐＨ７以上）に調整するだけの塩基触媒を合わせて添加するのが望ましい。 When an acid is added, when the reaction is carried out by reusing the aqueous layer portion, a base catalyst that simply adjusts the aqueous layer portion from neutral to alkaline side (pH 7 or more) in addition to the above amount of the base catalyst is used. It is desirable to add them together.
［化合物（７）の製造法］
上記製造法で得られた化合物（３）を原料とし、例えば特開昭５６−１４７７４０号公報に記載の方法により香料素材や生理活性剤として有用な化合物（７）を得ることができる。
[Method for producing compound (7)]
Using the compound (3) obtained by the above production method as a raw material, a compound (7) useful as a fragrance material or a physiologically active agent can be obtained, for example, by the method described in JP-A-56-147740.
具体的には、まず化合物（３）をシュウ酸等による脱水反応で化合物（４）を得、次いで、還流ｎ−ブタノール中、水性酸（塩酸又は臭化水素酸等）存在下で異性化反応させ、化合物（５）を得る。次いで、この化合物（５）と化合物（６）とを塩基性触媒存在下に反応させ、式（１０）で表される化合物（以下化合物（１０）という）を得る。 Specifically, the compound (3) is firstly dehydrated with oxalic acid or the like to obtain the compound (4), and then isomerized in refluxing n-butanol in the presence of an aqueous acid (such as hydrochloric acid or hydrobromic acid). To give compound (5). Next, the compound (5) and the compound (6) are reacted in the presence of a basic catalyst to obtain a compound represented by the formula (10) (hereinafter, referred to as compound (10)).
（式中、ｎ、Ｒ1及びＲ2は前記の意味を示す。）
化合物（５）に対して化合物（６）を、好ましくは１〜５モル倍、更に好ましくは１．２〜２モル倍の割合で反応させる。
(In the formula, n, R 1 and R 2 have the same meanings as described above.)
The compound (6) is reacted with the compound (5) at a ratio of preferably 1 to 5 moles, more preferably 1.2 to 2 moles.
塩基性触媒としては、ナトリウム、カリウム等のアルカリ金属、ナトリウムアルコキシド、カリウムアルコキシド等のアルカリ金属アルコキシド等が挙げられる。触媒の使用量は化合物（５）に対して０．００５〜０．２モル倍が好ましい。溶媒としてはアルコール類等の極性溶媒が好ましい。反応温度は−１０〜３０℃の範囲が好ましく、０〜２０℃の範囲が更に好ましい。 Examples of the basic catalyst include alkali metals such as sodium and potassium, and alkali metal alkoxides such as sodium alkoxide and potassium alkoxide. The amount of the catalyst to be used is preferably 0.005 to 0.2 mol times with respect to compound (5). As the solvent, a polar solvent such as an alcohol is preferable. The reaction temperature is preferably in the range of -10 to 30C, more preferably in the range of 0 to 20C.
次に、得られた化合物（１０）と水とを反応させることにより、化合物（７）を製造することができる。水は、化合物（１０）に対して１〜３モル倍量を反応系中に滴下しながら反応させることが好ましい。反応温度は１５０〜２５０℃の範囲が好ましい。 Next, the compound (7) can be produced by reacting the obtained compound (10) with water. It is preferable that water is reacted while being dripped in the reaction system in an amount of 1 to 3 times the molar amount of the compound (10). The reaction temperature is preferably in the range of 150 to 250 ° C.
［化合物（８）の製造法］
上記製造法で得られた化合物（３）を原料とし、既知の一般的な方法により、香料素材や生理活性剤として有用な化合物（８）を得ることができる。
[Production method of compound (8)]
Using the compound (3) obtained by the above production method as a raw material, a compound (8) useful as a fragrance material or a physiologically active agent can be obtained by a known general method.
例えば、化合物（７）の製造法と同様に、化合物（３）を脱水反応させて化合物（４）を得、化合物（４）を同様に異性化反応させ、化合物（５）を得る。次いで、Ｐｄ／Ｃ等の触媒存在下で水素還元させ、式（１１）で表される化合物（以下、化合物（１１）という）を得る。 For example, in the same manner as in the production method of compound (7), compound (3) is subjected to a dehydration reaction to obtain compound (4), and compound (4) is similarly subjected to isomerization reaction to obtain compound (5). Next, hydrogen reduction is performed in the presence of a catalyst such as Pd / C to obtain a compound represented by the formula (11) (hereinafter, referred to as compound (11)).
（式中、ｎ及びＲ1は前記の意味を示す。）
得られた化合物（１１）を、例えば特開平９−１０４６８１号公報に記載されているように、過酢酸等を酸化剤として用い、バイヤービリガー（Baeyer-Villiger）酸化させて、化合物（８）を得る。
(In the formula, n and R 1 have the same meanings as described above.)
The obtained compound (11) is oxidized with Baeyer-Villiger using peracetic acid or the like as an oxidizing agent, as described in, for example, JP-A-9-104681, to give compound (8). obtain.
実施例１
酸価３．４ｍｇ−ＫＯＨ／ｇのバレルアルデヒドを原料として用い、シクロペンタノン１１７．６ｇ（１．４モル）、水１２５．２ｇ、４８％ＮａＯＨ２．８ｇ（０．０３３モル）を５００ｍＬ４つ口フラスコに仕込み、撹拌しながら０℃に冷却した後、同温度でバレルアルデヒド７２．４ｇ（０．８４モル）を４時間かけて滴下した。滴下終了後、同温度で４時間撹拌した。反応終了後、１０％硫酸１７．４ｇで中和し、有機層をガスクロマトグラフィーで分析を行った。分析はメチルシリコンカラムを用い、標準物質としてジエチレングリコールモノエチルエーテル（カルビトール）を加えて行った。その結果、反応終了品中には、２−（１−ヒドロキシ−ｎ−ペンチル）シクロペンタノンが１２４．４ｇ（０．７３モル、収率８７．４％）、２−ペンチリデンシクロペンタノンが２．５ｇ（０．０１６モル）含まれていることがわかった。
Example 1
Using a valeraldehyde having an acid value of 3.4 mg-KOH / g as a raw material, four 500 mL ports of 117.6 g (1.4 mol) of cyclopentanone, 125.2 g of water, and 2.8 g (0.033 mol) of 48% NaOH were used. After charging the mixture in a flask and cooling to 0 ° C. with stirring, 72.4 g (0.84 mol) of valeraldehyde was added dropwise at the same temperature over 4 hours. After completion of the dropwise addition, the mixture was stirred at the same temperature for 4 hours. After the completion of the reaction, the mixture was neutralized with 17.4 g of 10% sulfuric acid, and the organic layer was analyzed by gas chromatography. The analysis was carried out using a methyl silicon column and adding diethylene glycol monoethyl ether (carbitol) as a standard substance. As a result, 124.4 g (0.73 mol, yield: 87.4%) of 2- (1-hydroxy-n-pentyl) cyclopentanone and 2-pentylidenecyclopentanone were contained in the reaction-completed product. It was found that 2.5 g (0.016 mol) was contained.
実施例２
酸価４．２ｍｇ−ＫＯＨ／ｇのバレルアルデヒドを原料として用い、シクロペンタノン７１９ｇ（８．５５モル）、水３２０ｇ、４８％ＮａＯＨ３．５ｇ（０．０４２モル）を２Ｌ４つ口フラスコに仕込み、撹拌しながら１５℃に冷却した後、同温度でバレルアルデヒド３１９ｇ（３．７０モル）を５時間かけて滴下した。滴下終了後、同温度で２時間撹拌した。反応終了後、中和し、実施例１と同様に分析した。その結果、反応終了品中には、２−（１−ヒドロキシ−ｎ−ペンチル）シクロペンタノンが５５７ｇ（３．２７モル、収率８９．０％）、２−ペンチリデンシクロペンタノンが６．８ｇ（０．０４４モル）含まれていることがわかった。
Example 2
Using a valeraldehyde having an acid value of 4.2 mg-KOH / g as a raw material, 719 g (8.55 mol) of cyclopentanone, 320 g of water, and 3.5 g (0.042 mol) of 48% NaOH were charged into a two-liter four-necked flask. After cooling to 15 ° C. while stirring, 319 g (3.70 mol) of valeraldehyde was added dropwise at the same temperature over 5 hours. After the addition, the mixture was stirred at the same temperature for 2 hours. After completion of the reaction, the mixture was neutralized and analyzed in the same manner as in Example 1. As a result, 557 g (3.27 mol, yield 89.0%) of 2- (1-hydroxy-n-pentyl) cyclopentanone and 2-pentylidenecyclopentanone were obtained in the reaction-completed product. It was found that 8 g (0.044 mol) was contained.
実施例３
酸価３．４ｍｇ−ＫＯＨ／ｇのバレルアルデヒドを原料として用い、シクロペンタノン７１９ｇ（８．５５モル）、水３２５ｇ、４８％ＮａＯＨ２．８ｇ（０．０３４モル）を２Ｌ４つ口フラスコに仕込み、撹拌しながら１５℃に冷却した後、同温度でバレルアルデヒド３３７ｇ（３．９１モル）を５時間かけて滴下した。滴下終了後、同温度で３時間撹拌した。反応終了後、中和し、実施例１と同様に分析した。その結果、反応終了品中には、２−（１−ヒドロキシ−ｎ−ペンチル）シクロペンタノンが５６２ｇ（３．３０モル、収率８５．０％）、２−ペンチリデンシクロペンタノンが９．５ｇ（０．０６３モル）含まれていることがわかった。
Example 3
Using valeraldehyde having an acid value of 3.4 mg-KOH / g as a raw material, 719 g (8.55 mol) of cyclopentanone, 325 g of water, and 2.8 g (0.034 mol) of 48% NaOH were charged into a 2 L four-necked flask, After cooling to 15 ° C. while stirring, 337 g (3.91 mol) of valeraldehyde was added dropwise at the same temperature over 5 hours. After completion of the dropwise addition, the mixture was stirred at the same temperature for 3 hours. After completion of the reaction, the mixture was neutralized and analyzed in the same manner as in Example 1. As a result, 562 g (3.30 mol, 85.0% yield) of 2- (1-hydroxy-n-pentyl) cyclopentanone and 9.2 g of 2-pentylidenecyclopentanone were contained in the reaction-completed product. It was found that 5 g (0.063 mol) was contained.
実施例４
酸価２．１ｍｇ−ＫＯＨ／ｇのバレルアルデヒドを原料として用い、シクロペンタノン１９９ｇ（２．３７モル）、水６０ｇ、４８％ＮａＯＨ１．２ｇ（０．０１４モル）を５００ｍＬ４つ口フラスコに仕込み、撹拌しながら１５℃に冷却した後、同温度でバレルアルデヒド６０ｇ（０．７０モル）を５時間かけて滴下した。滴下終了後、同温度で２時間撹拌した。反応終了後、中和し、実施例１と同様に分析した。その結果、反応終了品中には、２−（１−ヒドロキシ−ｎ−ペンチル）シクロペンタノンが１０７ｇ（０．６３モル、収率９０．５％）、２−ペンチリデンシクロペンタノンが２．０ｇ（０．０１３モル）含まれていることがわかった。
Example 4
Using valeraldehyde having an acid value of 2.1 mg-KOH / g as a raw material, 199 g (2.37 mol) of cyclopentanone, 60 g of water, and 1.2 g (0.014 mol) of 48% NaOH were charged into a 500 mL four-necked flask, After cooling to 15 ° C. while stirring, 60 g (0.70 mol) of valeraldehyde was added dropwise at the same temperature over 5 hours. After the addition, the mixture was stirred at the same temperature for 2 hours. After completion of the reaction, the mixture was neutralized and analyzed in the same manner as in Example 1. As a result, 107 g (0.63 mol, 90.5% yield) of 2- (1-hydroxy-n-pentyl) cyclopentanone and 2-pentylidenecyclopentanone were obtained in the reaction-completed product. It was found that 0 g (0.013 mol) was contained.
実施例５
酸価８．６ｍｇ−ＫＯＨ／ｇのバレルアルデヒドを原料として用い、シクロペンタノン７１９ｇ（８．５５モル）、水３２６ｇ、４８％ＮａＯＨ１０．０ｇ（０．０４６モル）を２Ｌ４つ口フラスコに仕込み、撹拌しながら１５℃に冷却した後、同温度でバレルアルデヒド３１９ｇ（３．７０モル）を５時間かけて滴下した。滴下終了後、同温度で４時間撹拌したが、未転化のバレルアルデヒドが残存し、収率が６５．３％であった。
Example 5
Using valeraldehyde having an acid value of 8.6 mg-KOH / g as a raw material, 719 g (8.55 mol) of cyclopentanone, 326 g of water, and 10.0 g (0.046 mol) of 48% NaOH were charged into a 2 L four-necked flask, After cooling to 15 ° C. while stirring, 319 g (3.70 mol) of valeraldehyde was added dropwise at the same temperature over 5 hours. After completion of the dropwise addition, the mixture was stirred at the same temperature for 4 hours, but unconverted valeraldehyde remained, and the yield was 65.3%.
そこで、４８％ＮａＯＨをさらに１５．８ｇ（０．１９モル）添加し、同温度で２時間撹拌した。反応終了後、中和し、実施例１と同様に分析した。その結果、反応終了品中には、２−（１−ヒドロキシ−ｎ−ペンチル）シクロペンタノンが５２１ｇ（３．０６モル、収率８３．８％）、２−ペンチリデンシクロペンタノンが１８．２ｇ（０．１１９モル）含まれていることがわかった。 Therefore, 15.8 g (0.19 mol) of 48% NaOH was further added, and the mixture was stirred at the same temperature for 2 hours. After completion of the reaction, the mixture was neutralized and analyzed in the same manner as in Example 1. As a result, 521 g (3.06 mol, 83.8% yield) of 2- (1-hydroxy-n-pentyl) cyclopentanone and 18.1 g of 2-pentylidenecyclopentanone were contained in the reaction-completed product. It was found that 2 g (0.119 mol) was contained.
比較例１
酸価７．３ｍｇ−ＫＯＨ／ｇのバレルアルデヒドを原料として用い、シクロペンタノン１７８ｇ（２．１４モル）、水８０ｇ、４８％ＮａＯＨ０．６２ｇ（０．００７モル）を５００ｍＬ４つ口フラスコに仕込み、撹拌しながら１５℃に冷却した後、同温度でバレルアルデヒド８０．４ｇ（０．９３モル）を５時間かけて滴下した。滴下終了後、同温度で３時間撹拌した。反応終了後、中和し、実施例１と同様に分析した。その結果、反応終了品中には、２−（１−ヒドロキシ−ｎ−ペンチル）シクロペンタノンが６２．９ｇ（０．３７モル、収率４０．０％）、２−ペンチリデンシクロペンタノンが０．５５ｇ（０．００４モル）含まれていることがわかった。
Comparative Example 1
Using valeraldehyde having an acid value of 7.3 mg-KOH / g as a raw material, 178 g (2.14 mol) of cyclopentanone, 80 g of water, and 0.62 g (0.007 mol) of 48% NaOH were charged into a 500 mL four-necked flask. After cooling to 15 ° C. while stirring, 80.4 g (0.93 mol) of valeraldehyde was added dropwise at the same temperature over 5 hours. After completion of the dropwise addition, the mixture was stirred at the same temperature for 3 hours. After completion of the reaction, the mixture was neutralized and analyzed in the same manner as in Example 1. As a result, 62.9 g (0.37 mol, 40.0% yield) of 2- (1-hydroxy-n-pentyl) cyclopentanone and 2-pentylidenecyclopentanone were contained in the reaction-completed product. It was found that the content was 0.55 g (0.004 mol).
実施例１〜５及び比較例１の反応条件及び結果をまとめて表１に示す。 Table 1 summarizes the reaction conditions and results of Examples 1 to 5 and Comparative Example 1.
実施例６
（ａ）酸価１．０ｍｇ−ＫＯＨ／ｇのバレルアルデヒドを原料として用い、シクロペンタノン１１２．３ｇ（１．３４モル）、水５０．０ｇ、４８％ＮａＯＨ０．２４ｇ（０．００２９モル）を５００ｍＬ４つ口フラスコに仕込み、撹拌しながら１５℃に冷却した後、同温度でバレルアルデヒド５０．０ｇ（０．５８モル）を５時間かけて滴下した。滴下終了後、同温度で２時間撹拌した。反応終了後、１０５％縮合リン酸０．２３ｇ（０．００２５モル）で中和し、４０℃で分層した。有機層は１７０．４ｇ、水層は４２．４ｇ得られた。水層のｐＨは５．５であった。有機層について、実施例１と同様に分析した。その結果、反応終了品中には、２−（１−ヒドロキシ−ｎ−ペンチル）シクロペンタノンが８６．０ｇ（０．５０５モル、収率８７．２％）、２−ペンチリデンシクロペンタノンが２．２９ｇ（０．０１５モル）、シクロペンタノンダイマーが１．９ｇ（０．０１１モル、含量１．１％）含まれており、水層部には２．８ｇのシクロペンタノンが含まれていることがわかった。さらに、有機層から蒸留によって５８．３ｇのシクロペンタノンと８ｇの水が回収できた。また、水層部に含まれるリン酸をリン酸３ナトリウムにするためのＮａＯＨ量を滴定によって求めると、０．００６２モルであった。
Example 6
(A) Using valeraldehyde having an acid value of 1.0 mg-KOH / g as a raw material, 112.3 g (1.34 mol) of cyclopentanone, 50.0 g of water, and 0.24 g (0.0029 mol) of 48% NaOH were used. After charging to a 500 mL four-necked flask and cooling to 15 ° C. while stirring, 50.0 g (0.58 mol) of valeraldehyde was added dropwise at the same temperature over 5 hours. After the addition, the mixture was stirred at the same temperature for 2 hours. After the completion of the reaction, the mixture was neutralized with 0.23 g (0.0025 mol) of 105% condensed phosphoric acid, and separated at 40 ° C. 170.4 g of the organic layer and 42.4 g of the aqueous layer were obtained. The pH of the aqueous layer was 5.5. The organic layer was analyzed in the same manner as in Example 1. As a result, 86.0 g (0.505 mol, 87.2% yield) of 2- (1-hydroxy-n-pentyl) cyclopentanone and 2-pentylidenecyclopentanone were contained in the reaction-completed product. It contains 2.29 g (0.015 mol) and 1.9 g (0.011 mol, content 1.1%) of cyclopentanone dimer, and 2.8 g of cyclopentanone is contained in the aqueous layer. I understood that. Further, 58.3 g of cyclopentanone and 8 g of water could be recovered from the organic layer by distillation. Further, the amount of NaOH for converting the phosphoric acid contained in the aqueous layer portion into trisodium phosphate was determined by titration to be 0.0062 mol.
（ｂ）次に、（ａ）の水層部と蒸留留分を５００ｍＬ４つ口フラスコに仕込み、さらにここに、シクロペンタノン５１．１ｇ（再使用分を含め１．３４モル）と、添加したリン酸をリン酸３ナトリウムにするための分を含めて、４８％ＮａＯＨ０．８７ｇ（０．０１０５モル）を仕込み、撹拌しながら１５℃に冷却した後、同温度でバレルアルデヒド５０．０ｇ（０．５８モル）を５時間かけて滴下した。滴下終了後、同温度で２時間撹拌した。反応終了後、１０５％縮合リン酸０．８４ｇ（０．００９モル）で中和し、４０℃で分層した。水層のｐＨは５．５であった。有機層は１７１．２ｇ、水層は４．３３ｇ得られた。有機層について、実施例１と同様に分析した。その結果、反応終了品中には、２−（１−ヒドロキシ−ｎ−ペンチル）シクロペンタノンが８３．５ｇ（０．４９０モル、収率８４．６％）、２−ペンチリデンシクロペンタノンが２．２８ｇ（０．０１５モル）含まれていることがわかった。さらに、有機層から蒸留によって６１．７ｇのシクロペンタノンと８．５ｇの水が回収できた。また、水層部に含まれるリン酸をリン酸３ナトリウムにするためのＮａＯＨ量を滴定によって求めると、０．０２８モルであった。 (B) Next, the aqueous layer portion and the distillation fraction of (a) were charged into a 500 mL four-necked flask, and 51.1 g of cyclopentanone (1.34 mol including reuse) was further added thereto. 0.87 g (0.0105 mol) of 48% NaOH was charged, including a portion for converting phosphoric acid to trisodium phosphate, cooled to 15 ° C. while stirring, and then 50.0 g (0%) of valeraldehyde was added at the same temperature. .58 mol) was added dropwise over 5 hours. After the addition, the mixture was stirred at the same temperature for 2 hours. After completion of the reaction, the mixture was neutralized with 0.84 g (0.009 mol) of 105% condensed phosphoric acid, and separated at 40 ° C. The pH of the aqueous layer was 5.5. 171.2 g of an organic layer and 4.33 g of an aqueous layer were obtained. The organic layer was analyzed in the same manner as in Example 1. As a result, 83.5 g (0.490 mol, 84.6% yield) of 2- (1-hydroxy-n-pentyl) cyclopentanone and 2-pentylidenecyclopentanone were contained in the reaction-completed product. It was found that 2.28 g (0.015 mol) was contained. Further, 61.7 g of cyclopentanone and 8.5 g of water could be recovered from the organic layer by distillation. In addition, the amount of NaOH for converting the phosphoric acid contained in the aqueous layer into trisodium phosphate was determined by titration to be 0.028 mol.
（ｃ）さらに、（ｂ）の水層部と蒸留留分を５００ｍＬ４つ口フラスコに仕込み、さらにここに、シクロペンタノン４８．２ｇ（再使用分を含め１．３４モル）と、添加したリン酸をリン酸３ナトリウムにするための分を含めて、４８％ＮａＯＨ１．９６ｇ（０．０２３６モル）を仕込み、撹拌しながら１５℃に冷却した後、同温度でバレルアルデヒド５０．０ｇ（０．５８モル）を５時間かけて滴下した。滴下終了後、同温度で２時間撹拌した。反応終了後、１０５％縮合リン酸１．８９ｇ（０．０２０３モル）で中和し、４０℃で分層した。水層のｐＨは５．５であった。有機層は１７０．７ｇ、水層は４．７２ｇ得られた。有機層について、実施例１と同様に分析した。その結果、反応終了品中には、２−（１−ヒドロキシ−ｎ−ペンチル）シクロペンタノンが８２．４ｇ（０．４８４モル、収率８３．５％）、２−ペンチリデンシクロペンタノンが２．２５ｇ（０．０１５モル）含まれていることがわかった。 (C) Further, the aqueous layer part and the distillation fraction of (b) were charged into a 500 mL four-necked flask, and 48.2 g of cyclopentanone (1.34 mol including reuse) was added thereto. 1.96 g (0.0236 mol) of 48% NaOH was charged, including the amount for converting the acid to trisodium phosphate, cooled to 15 ° C. with stirring, and then 50.0 g of valeraldehyde (0. 58 mol) was added dropwise over 5 hours. After the addition, the mixture was stirred at the same temperature for 2 hours. After the completion of the reaction, the mixture was neutralized with 1.89 g (0.0203 mol) of 105% condensed phosphoric acid, and separated at 40 ° C. The pH of the aqueous layer was 5.5. 170.7 g of the organic layer and 4.72 g of the aqueous layer were obtained. The organic layer was analyzed in the same manner as in Example 1. As a result, 82.4 g (0.484 mol, yield 83.5%) of 2- (1-hydroxy-n-pentyl) cyclopentanone and 2-pentylidenecyclopentanone were contained in the reaction-completed product. It was found that 2.25 g (0.015 mol) was contained.
比較例２
（ａ）酸価７．５ｍｇ−ＫＯＨ／ｇのバレルアルデヒドを原料として用い、シクロペンタノン２２４．６ｇ（２．６７モル）、水１００ｇ、４８％ＮａＯＨ９．７ｇ（０．１１６モル）を１Ｌ４つ口フラスコに仕込み、撹拌しながら１５℃に冷却した後、同温度でバレルアルデヒド１００ｇ（１．１６モル）を５時間かけて滴下した。滴下終了後、同温度で２時間撹拌した。反応終了後、１０５％縮合リン酸９．３ｇ（０．１００モル）で中和し、４０℃で分層した。有機層は３４３．７ｇ、水層は９９．９ｇ得られた。水層のｐＨは５．５であった。有機層について、実施例１と同様に分析した。その結果、反応終了品中には、２−（１−ヒドロキシ−ｎ−ペンチル）シクロペンタノンが１６５．８ｇ（０．９７４モル、収率８４．９％）、２−ペンチリデンシクロペンタノンが４．５８ｇ（０．０３０モル）、シクロペンタノンダイマーが１０．１ｇ（０．０６０モル、含量２．９％）含まれており、水層部には６．７ｇのシクロペンタノンが含まれていることがわかった。さらに、有機層から蒸留によって１１６．７ｇのシクロペンタノンと１６ｇの水が回収できた。また、水層部に含まれるリン酸をリン酸３ナトリウムにするためのＮａＯＨ量を滴定によって求めると、０．２５１モルであった。
Comparative Example 2
(A) Using valeraldehyde having an acid value of 7.5 mg-KOH / g as a raw material, four 1 L of 224.6 g (2.67 mol) of cyclopentanone, 100 g of water, and 9.7 g (0.116 mol) of 48% NaOH were used. After charging into a neck flask and cooling to 15 ° C. while stirring, 100 g (1.16 mol) of valeraldehyde was added dropwise at the same temperature over 5 hours. After completion of the dropwise addition, the mixture was stirred at the same temperature for 2 hours. After the completion of the reaction, the mixture was neutralized with 9.3 g (0.100 mol) of 105% condensed phosphoric acid, and separated at 40 ° C. 343.7 g of an organic layer and 99.9 g of an aqueous layer were obtained. The pH of the aqueous layer was 5.5. The organic layer was analyzed in the same manner as in Example 1. As a result, 165.8 g (0.974 mol, 84.9% yield) of 2- (1-hydroxy-n-pentyl) cyclopentanone and 2-pentylidenecyclopentanone were contained in the reaction-completed product. It contains 4.58 g (0.030 mol) and 10.1 g (0.060 mol, content 2.9%) of cyclopentanone dimer, and the aqueous layer contains 6.7 g of cyclopentanone. I understood that. Further, 116.7 g of cyclopentanone and 16 g of water could be recovered from the organic layer by distillation. The amount of NaOH required to convert phosphoric acid contained in the aqueous layer into trisodium phosphate was determined by titration to be 0.251 mol.
（ｂ）次に、（ａ）の水層部と蒸留留分を１Ｌ４つ口フラスコに仕込み、さらにここに、シクロペンタノン２２４．６ｇ（再使用分を含め２．６７モル）と、添加したリン酸をリン酸３ナトリウムにするための分を含めて、４８％ＮａＯＨ２２．６ｇ（０．２７１モル）を仕込み、撹拌しながら１５℃に冷却した後、同温度でバレルアルデヒド１００ｇ（１．１６モル）を５時間かけて滴下した。滴下終了後、同温度で２時間撹拌した。反応終了後、１０５％縮合リン酸２１．７ｇ（０．２３３モル）で中和し、４０℃で分層した。水層のｐＨは５．５であった。有機層は３４８．８ｇ、水層は１２３．２ｇ得られた。有機層について、実施例１と同様に分析した。その結果、反応終了品中には、２−（１−ヒドロキシ−ｎ−ペンチル）シクロペンタノンが１１３．５ｇ（０．６６７モル、収率５８．１％）、２−ペンチリデンシクロペンタノンが４．５６ｇ（０．０３０モル）含まれていることがわかった。 (B) Next, the aqueous layer portion and the distillation fraction of (a) were charged into a 1 L four-necked flask, and 224.6 g of cyclopentanone (2.67 mol including reuse) was further added thereto. After adding 22.6 g (0.271 mol) of 48% NaOH, including a portion for converting phosphoric acid into trisodium phosphate, the mixture was cooled to 15 ° C. with stirring, and then 100 g (1.16 mol) of valeraldehyde was added at the same temperature. Mol) was added dropwise over 5 hours. After the addition, the mixture was stirred at the same temperature for 2 hours. After completion of the reaction, the mixture was neutralized with 21.7 g (0.233 mol) of 105% condensed phosphoric acid, and the mixture was separated at 40 ° C. The pH of the aqueous layer was 5.5. 348.8 g of an organic layer and 123.2 g of an aqueous layer were obtained. The organic layer was analyzed in the same manner as in Example 1. As a result, in the finished product, 113.5 g (0.667 mol, yield: 58.1%) of 2- (1-hydroxy-n-pentyl) cyclopentanone and 2-pentylidenecyclopentanone were contained. It was found that 4.56 g (0.030 mol) was contained.
実施例６及び比較例２の反応条件及び結果をまとめて表２に示す。 Table 2 summarizes the reaction conditions and results of Example 6 and Comparative Example 2.
表２から明らかなように、実施例６及び比較例２の（ａ）工程におけるＡとＢの差（Ａ−Ｂ）がアルデヒド１モルに対し、実施例６では０．０６モル以下であるが、比較例２では０．０６モルより大きい。従って、比較例２の（ａ）工程ではシクロペンタノンダイマー含量が多く、水層部を再使用した（ｂ）工程では実施例６に比べて収率が低下している。 As is clear from Table 2, the difference (AB) between A and B in the step (a) of Example 6 and Comparative Example 2 is 0.06 mol or less in Example 6 with respect to 1 mol of aldehyde. In Comparative Example 2, it is larger than 0.06 mol. Therefore, the cyclopentanone dimer content is high in the step (a) of Comparative Example 2, and the yield is lower than that of Example 6 in the step (b) in which the aqueous layer is reused.
実施例７
実施例１の反応を２回行って得たものを蒸留してシクロペンタノンと水を回収し、そのうち２−（１−ヒドロキシ−ｎ−ペンチル）シクロペンタノン１．０１モル及び２−ペンチリデンシクロペンタノン０．０２２モルにシュウ酸を０．０２０６モル添加して１２０℃にて反応した。この中に含まれる２−ペンチリデンシクロペンタノンは１４１ｇ（０．９３ｍｏｌ）であった。この濾過終了物をｎ−ブタノール１５３ｇに溶かし、１３０℃に昇温した後、同温度で３−ピコリン１４．５ｇ（０．１５ｍｏｌ）と３５％塩酸１０．５ｇ（０．１ｍｏｌ）の混合液を３０分で滴下した。滴下終了後、同温度で３．５時間加熱攪拌した。反応終了後、室温まで冷却し、水酸化ナトリウム水溶液で中和した後、有機層を分析した結果、反応終了品中には、２−ペンチル−２−シクロペンテノンが１１８ｇ含まれていることがわかった。この異性化反応の収率は８３％であった。
Example 7
The product obtained by performing the reaction of Example 1 twice was distilled to recover cyclopentanone and water, of which 1.01 mol of 2- (1-hydroxy-n-pentyl) cyclopentanone and 2-pentylidene were obtained. 0.0206 mol of oxalic acid was added to 0.022 mol of cyclopentanone and reacted at 120 ° C. The amount of 2-pentylidenecyclopentanone contained therein was 141 g (0.93 mol). This filtered product was dissolved in 153 g of n-butanol and heated to 130 ° C., and then a mixture of 14.5 g (0.15 mol) of 3-picoline and 10.5 g (0.1 mol) of 35% hydrochloric acid was heated at the same temperature. It was dropped in 30 minutes. After completion of the dropwise addition, the mixture was heated and stirred at the same temperature for 3.5 hours. After completion of the reaction, the mixture was cooled to room temperature, neutralized with an aqueous sodium hydroxide solution, and analyzed for the organic layer. As a result, it was found that the reaction-completed product contained 118 g of 2-pentyl-2-cyclopentenone. all right. The yield of this isomerization reaction was 83%.
この反応終了品から、２−ペンチル−２−シクロペンテノンを９５ｇ（０．６ｍｏｌ）精製した。さらに、窒素雰囲気下にてマロン酸ジメチル１１８ｇ（０．９ｍｏｌ）を無水メタノール３８ｇに溶解し、０℃に冷却して、ナトリウムメトキシド（３０％メタノール溶液）６．５ｇ（０．０３６ｍｏｌ）を添加したものに、上記で得られた２−ペンチル−２−シクロペンテノン９５ｇ（０．６ｍｏｌ）を０℃で、２時間かけて滴下した。滴下終了後、同温度で３時間撹拌した。未反応のマロン酸ジメチルを減圧留去し、１６０ｇのマイケル付加物を得た。 From the reaction product, 95 g (0.6 mol) of 2-pentyl-2-cyclopentenone was purified. Further, under a nitrogen atmosphere, 118 g (0.9 mol) of dimethyl malonate was dissolved in 38 g of anhydrous methanol, cooled to 0 ° C, and 6.5 g (0.036 mol) of sodium methoxide (30% methanol solution) was added. To the solution, 95 g (0.6 mol) of 2-pentyl-2-cyclopentenone obtained above was added dropwise at 0 ° C over 2 hours. After completion of the dropwise addition, the mixture was stirred at the same temperature for 3 hours. Unreacted dimethyl malonate was distilled off under reduced pressure to obtain 160 g of Michael adduct.
蒸留留出管をつけた反応装置に、上記で得られたマイケル付加物を加え、２１５℃に加熱し、水を３．２ｇ／ｈ（２％／ｈ）の速度で滴下した。発生する二酸化炭素とメタノールを留出させながら、２１５℃で、４時間滴下反応を行った。反応終了後、粗生成物１２６ｇ中に、３−オキソ−２−ペンチルシクロペンチル酢酸メチル１２３ｇを得た。全工程収率は６０％であった。 The Michael adduct obtained above was added to a reactor equipped with a distillation distilling tube, heated to 215 ° C., and water was added dropwise at a rate of 3.2 g / h (2% / h). While distilling off the generated carbon dioxide and methanol, a dropping reaction was performed at 215 ° C. for 4 hours. After completion of the reaction, 123 g of methyl 3-oxo-2-pentylcyclopentylacetate was obtained in 126 g of the crude product. The overall process yield was 60%.
粗生成物を精留して得られた３−オキソ−２−ペンチルシクロペンチル酢酸メチルは、フルーティでジャスミン様の香気を有しており、香料素材としても優れたものであった。 Methyl 3-oxo-2-pentylcyclopentyl acetate obtained by rectifying the crude product had a fruity and jasmine-like odor, and was also excellent as a fragrance material.
比較例３
比較例１の反応を３回行って得たものを蒸留してシクロペンタノンと水を回収し、そのうち２−（１−ヒドロキシ−ｎ−ペンチル）シクロペンタノン１．１１モル及び２−ペンチリデンシクロペンタノン０．０１２モルにシュウ酸を０．０２０６モル添加して１２０℃にて反応した。その後、実施例７と同様に反応を行って３−オキソ−２−ペンチルシクロペンチル酢酸メチルを得た。その結果、全工程収率は２８％であった。
Comparative Example 3
The product obtained by performing the reaction of Comparative Example 1 three times was distilled to recover cyclopentanone and water, of which 1.11 mol of 2- (1-hydroxy-n-pentyl) cyclopentanone and 2-pentylidene were obtained. 0.0206 mol of oxalic acid was added to 0.012 mol of cyclopentanone and reacted at 120 ° C. Thereafter, the reaction was carried out in the same manner as in Example 7 to obtain methyl 3-oxo-2-pentylcyclopentyl acetate. As a result, the overall process yield was 28%.
Claims (7)
で表される２−（アルキリデン）シクロアルカノン及び／又は２−（アリーレン）シクロアルカノン（以下化合物（４）という）を得、次いで異性化反応させて、式（５）
で表される２−（アルキル）シクロアルケノン及び／又は２−（アリール）シクロアルケノン（以下化合物（５）という）とし、次いで式（６）
で表されるマロン酸ジエステルと反応させ、次いで水を反応させる、式（７）
で表されるアルキル（３−オキソ−２−アルキルシクロアルキル）アセテート及び／又はアルキル（３−オキソ−２−アリールシクロアルキル）アセテートの製造法。 The compound (3) obtained by the production method according to any one of claims 1 to 5 is subjected to a dehydration reaction to obtain a compound of the formula (4)
2- (alkylidene) cycloalkanone and / or 2- (arylene) cycloalkanone (hereinafter referred to as compound (4)) represented by the formula
2- (alkyl) cycloalkenones and / or 2- (aryl) cycloalkenones (hereinafter referred to as compound (5)) represented by the following formula:
Reacting with malonic diester represented by the formula:
A method for producing an alkyl (3-oxo-2-alkylcycloalkyl) acetate and / or an alkyl (3-oxo-2-arylcycloalkyl) acetate represented by the formula:
The compound (3) obtained by the production method according to any one of claims 1 to 5 is subjected to a dehydration reaction to obtain a compound (4), and then isomerized to give a compound (5). A method for producing a 5-alkyl-5-alkanolide and / or a 5-aryl-5-alkanolide represented by the formula (8), wherein the hydrogen reduction is followed by Bayer-Villiger oxidation.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004262826A (en) * | 2003-02-28 | 2004-09-24 | Japan Science & Technology Agency | Method for producing hydroxy ketone compound |
| JP2005255646A (en) * | 2004-03-15 | 2005-09-22 | Kao Corp | Cycloalkanones-containing composition |
| WO2009084504A1 (en) | 2007-12-28 | 2009-07-09 | Kao Corporation | Process for producing 2-(1-hydroxyalkyl)cycloalkanone |
| JP2009155233A (en) * | 2007-12-25 | 2009-07-16 | Kao Corp | Method for producing mixture of 2-(1-hydroxyalkyl)cycloalkanone and dehydrated material of the same |
| JP2009155232A (en) * | 2007-12-25 | 2009-07-16 | Kao Corp | Method for producing mixture of 2-(1-hydroxyalkyl)cycloalkanone and dehydrated material of the same |
| WO2014156783A1 (en) | 2013-03-29 | 2014-10-02 | 日本ゼオン株式会社 | Fragrance composition and method for producing same |
Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56147740A (en) * | 1980-01-18 | 1981-11-16 | Int Flavors & Fragrances Inc | Manufacture of methyldihydrojasmonate and homologue |
| JPS615041A (en) * | 1984-06-18 | 1986-01-10 | Mitsubishi Chem Ind Ltd | Production of 2-(1-hydroxyalkyl)cyclohexanone |
| JPH05132694A (en) * | 1991-05-15 | 1993-05-28 | Givaudan Roure Internatl Sa | Perfuming agent composition and flavoring composition |
| JPH09104681A (en) * | 1995-10-06 | 1997-04-22 | Nippon Peroxide Co Ltd | Production of delta-lactone |
| JP2001328965A (en) * | 2000-03-15 | 2001-11-27 | Kao Corp | Method for producing jasmonate derivative and intermediate thereof |
| JP2001335529A (en) * | 2000-05-29 | 2001-12-04 | Nippon Zeon Co Ltd | Method for producing 2-(1-hydroxyalkyl)cycloalkanone |
| JP2004203844A (en) * | 2002-12-26 | 2004-07-22 | Kao Corp | Method for production of 2-(alkylidene)cycloalkanone |
| JP2004217620A (en) * | 2002-12-26 | 2004-08-05 | Kao Corp | Method for producing 2-(alkyl)cycloalkenone |
| JP2005126445A (en) * | 2000-03-15 | 2005-05-19 | Kao Corp | Method for producing jasmonic acid ester derivative and intermediate thereof |
-
2003
- 2003-11-10 JP JP2003379321A patent/JP4615206B2/en not_active Expired - Lifetime
Patent Citations (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS56147740A (en) * | 1980-01-18 | 1981-11-16 | Int Flavors & Fragrances Inc | Manufacture of methyldihydrojasmonate and homologue |
| JPS615041A (en) * | 1984-06-18 | 1986-01-10 | Mitsubishi Chem Ind Ltd | Production of 2-(1-hydroxyalkyl)cyclohexanone |
| JPH05132694A (en) * | 1991-05-15 | 1993-05-28 | Givaudan Roure Internatl Sa | Perfuming agent composition and flavoring composition |
| JPH09104681A (en) * | 1995-10-06 | 1997-04-22 | Nippon Peroxide Co Ltd | Production of delta-lactone |
| JP2001328965A (en) * | 2000-03-15 | 2001-11-27 | Kao Corp | Method for producing jasmonate derivative and intermediate thereof |
| JP2005126445A (en) * | 2000-03-15 | 2005-05-19 | Kao Corp | Method for producing jasmonic acid ester derivative and intermediate thereof |
| JP2001335529A (en) * | 2000-05-29 | 2001-12-04 | Nippon Zeon Co Ltd | Method for producing 2-(1-hydroxyalkyl)cycloalkanone |
| JP2004203844A (en) * | 2002-12-26 | 2004-07-22 | Kao Corp | Method for production of 2-(alkylidene)cycloalkanone |
| JP2004217620A (en) * | 2002-12-26 | 2004-08-05 | Kao Corp | Method for producing 2-(alkyl)cycloalkenone |
Cited By (11)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2004262826A (en) * | 2003-02-28 | 2004-09-24 | Japan Science & Technology Agency | Method for producing hydroxy ketone compound |
| JP2005255646A (en) * | 2004-03-15 | 2005-09-22 | Kao Corp | Cycloalkanones-containing composition |
| JP4651959B2 (en) * | 2004-03-15 | 2011-03-16 | 花王株式会社 | Cycloalkanone-containing composition |
| JP2009155233A (en) * | 2007-12-25 | 2009-07-16 | Kao Corp | Method for producing mixture of 2-(1-hydroxyalkyl)cycloalkanone and dehydrated material of the same |
| JP2009155232A (en) * | 2007-12-25 | 2009-07-16 | Kao Corp | Method for producing mixture of 2-(1-hydroxyalkyl)cycloalkanone and dehydrated material of the same |
| WO2009084504A1 (en) | 2007-12-28 | 2009-07-09 | Kao Corporation | Process for producing 2-(1-hydroxyalkyl)cycloalkanone |
| JP2009161463A (en) * | 2007-12-28 | 2009-07-23 | Kao Corp | Method for producing 2-(1-hydroxyalkyl)cycloalkanone |
| US8367874B2 (en) | 2007-12-28 | 2013-02-05 | Kao Corporation | Process for producing 2-(1-hydroxyalkyl)cycloalkanone |
| WO2014156783A1 (en) | 2013-03-29 | 2014-10-02 | 日本ゼオン株式会社 | Fragrance composition and method for producing same |
| KR20150136115A (en) | 2013-03-29 | 2015-12-04 | 제온 코포레이션 | Fragrance composition and method for producing same |
| US9708569B2 (en) | 2013-03-29 | 2017-07-18 | Zeon Corporation | Fragrance composition and method for producing same |
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