JP2002326971A - Method of production for optically active chrysanthemumic acid - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an advantageous method of production for an optically active chrysanthemumic acid. SOLUTION: This method of production for the optically active chrysanthemumic acid reacts an optically active organic amine to the chrysanthemumic acid having a trans isomer ratio >=70% and optical purity of the trans isomer less than 2-10%e.e. and then carrying out an optical resolution. The optically active organic amine is expressed, for example by general formula (1) or general formula (2). (R<1> and R<2> are each independently H, an alkyl group or the like, X and Y are each independently H, a halogen atom or the like, * is an asymmetric carbon atom in the formula (1)) and (R<1> and R<2> have same meaning as the previous description; R<3> is an alkyl group; R<4> and R<5> are each H or the like; and * is an asymmetric carbon atom in the formula (2)).

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a method for producing optically active chrysanthemic acid.

[0002]

2. Description of the Related Art (+)-2,2-dimethyl-3- (2-
Methyl-1-propenyl) cyclopropanecarboxylic acid (hereinafter abbreviated as (+)-ryunic acid) is extremely important as a compound constituting an acid component of a synthetic pyrethroid insecticide. The insecticidal effect as an insecticide is higher in the case where the trans-form chrysanthemic acid is used as the acid component than in the case where the cis-form chrysantic acid is used as the acid component. Things show an outstanding insecticidal effect,
It was very important to industrially produce chrysanthemic acid rich in (+)-trans chrysanthemic acid or (+)-trans form.

As a method for producing optically active chrysanthemic acid, for example, an optical resolution method using (±) -trans chrysanthemic acid or a trans-rich racemic chrysanthemic acid as a raw material is known (Japanese Patent Publication No. 46-20382). JP-B-54-37130; JP-A-49-109344;
No. 23497), but the trans-form optical purity, which is relatively easy to prepare, is 2 to 10% e. e. A method for efficiently obtaining chrysanthemic acid having high optical purity by using less than chrysanthemic acid as a raw material by optical resolution has not been known.

[0004]

Under these circumstances, the present inventors have found that the optical purity of the trans isomer, which is relatively easy to prepare, is 2 to 10% e.g. e. A method for efficiently obtaining chrysanthemic acid having high optical purity by optical resolution using less than chrysanthemic acid as a raw material has been intensively studied. The trans optical purity is 2 to 10% e.g. e. It was found that by performing optical resolution using chrysanthemic acid having a trans-form ratio of less than 70% and having a trans-form ratio of 70% or more as a raw material, chrysanthemic acid having high optical purity can be obtained efficiently and in good yield. Invented the invention.

[0005]

That is, the present invention provides a trans-isomer ratio of 70% or more and a trans-isomer optical purity of 2 to 10% e.g. e. The present invention provides a process for producing optically active chrysanthemic acid, which comprises optically resolving chrysanthemic acid by allowing an optically active organic amine to act on chrysanthemic acid.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION The raw material of the present invention has a trans isomer ratio of 70% or more and a trans isomer optical purity of 2-1.
0% e. e. An optically active chrysanthemic acid (hereinafter abbreviated as a raw material chrysanthemic acid) is reacted with an optically active organic amine to optically resolve the chrysanthemic acid to obtain an optically active chrysanthemic acid. As a raw material chrysanthemic acid, trans form ratio is 75-9
8%, and the trans optical purity is 2.5 to 10%
e. e. It is preferable to use less chrysanthemic acid in that optically active chrysanthemic acid can be obtained more efficiently.

As the optically active organic amine, for example, a compound represented by the general formula (1) (Wherein, R ¹ and R ² are the same or different and each represents a hydrogen atom, an alkyl group or an aralkyl group. Here, the aralkyl group may be substituted with a hydroxyl group, an alkyl group or an alkoxy group. X and Y are the same or different and each represent a hydrogen atom, a halogen atom, an alkyl group or an alkoxy group; * represents an asymmetric carbon atom) (hereinafter, optically active organic amine) Abbreviated as organic amine (1)) or the general formula (2) (Wherein, R ¹ and R ² have the same meanings as described above;
³ represents an alkyl group. R ⁴ and R ⁵ each represent a hydrogen atom, or R ⁴ and R ⁵ combine to form a benzene ring together with the bonded carbon atoms. * Represents an asymmetric carbon atom. ) (Hereinafter abbreviated as optically active organic amine (2)).

In the formula of the optically active organic amine (1) or the optically active organic amine (2), examples of the alkyl group include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group and an isobutyl group. , A sec-butyl group, a tert-butyl group, an n-pentyl group, an n-hexyl group, and other alkyl groups having 1 to 6 carbon atoms. Examples of the aralkyl group include a benzyl group, a 1-phenylethyl group, -An aralkyl group having 7 to 10 carbon atoms such as a phenylethyl group, a phenylpropyl group and a phenylbutyl group. Such an aralkyl group may be substituted with a hydroxyl group, an alkyl group or an alkoxy group, and examples of the alkyl group include the same as those described above.Examples of the alkoxy group include a methoxy group, an ethoxy group,
n-propoxy group, isopropoxy group, n-butoxy group, isobutoxy group, sec-butoxy group, tert-
An alkoxy group having 1 to 4 carbon atoms such as a butoxy group is exemplified. Examples of the halogen atom include a fluorine atom, a chlorine atom, and a bromine atom. Examples of such an aralkyl group substituted with a hydroxyl group, an alkyl group or an alkoxy group include a p-hydroxybenzyl group and a 2-hydroxy-3-methoxybenzyl group.

The optically active organic amine (1) or (2) is, for example, (S) -1-
Phenyl-2- (p-tolyl) ethylamine, (S)-
α- (1-naphthyl) ethylamine, (S) -α- (2
-Naphthyl) ethylamine, (S) -1-phenylethylamine, (S) -N- (p-hydroxybenzyl)-
1-phenylethylamine, (S) -N- (p-hydroxybenzyl) -1- (p-tolyl) ethylamine,
(S) -N- (p-hydroxybenzyl) -1- (p-
Isopropylphenyl) ethylamine, (S) -N-
(P-hydroxybenzyl) -1- (p-nitrophenyl) ethylamine, (S) -N- (p-hydroxybenzyl) -1- (p-bromophenyl) ethylamine,
(S) -N- (p-hydroxybenzyl) -1- (1-
Naphthyl) ethylamine, (S) -N- (p-hydroxybenzyl) -1- (p-methoxyphenyl) ethylamine, (S) -N- (p-hydroxybenzyl) -1-
Phenylpropylamine,

(S) -N- (2-hydroxy-3-methoxybenzyl) -1-phenylethylamine, (S)-
N- (2-hydroxy-3-methoxybenzyl) -1-
(P-tolyl) ethylamine, (S) -N- (2-hydroxy-3-methoxybenzyl) -1- (p-isopropylphenyl) ethylamine, (S) -N- (2-hydroxy-3-methoxybenzyl) -1- (p-nitrophenyl) ethylamine, (S) -N- (2-hydroxy-3-methoxybenzyl) -1- (p-bromophenyl) ethylamine, (S) -N- (2-hydroxy-3
-Methoxybenzyl) -1- (1-naphthyl) ethylamine, (S) -N- (2-hydroxy-3-methoxybenzyl) -1- (p-methoxyphenyl) ethylamine, (S) -N- (2- (Hydroxy-3-methoxybenzyl) -1-phenylpropylamine, (S) -N-
(2-hydroxy-3-methoxybenzyl) -2-methyl-1-phenylpropylamine and the like, and those compounds in which (S)-is replaced by (R)-,
The (S) -form optically active organic amine is preferred.

The optical resolution is usually performed in a solvent. Examples of the solvent include aromatic hydrocarbon solvents such as toluene and xylene; aliphatic hydrocarbon solvents such as hexane and heptane; alcohol solvents such as methanol and ethanol; and ketone solvents such as acetone and methyl isobutyl ketone. Solvents include, for example, ether solvents such as dioxane and tetrahydrofuran, and single or mixed solvents such as water. The amount of the solvent used varies depending on the type of the solvent, the post-treatment conditions, and the like, and is not particularly limited. An optimal amount is selected depending on each condition.

The amount of the optically active organic amine to be used is usually 0.3 to 1.2 mol times, preferably 0.1 mol, per mol of the raw material chrysanthemic acid.
It is 4-1.1 mole times.

The optical resolution may be attained by mixing and contacting the raw material chrysanthemic acid and the optically active organic amine in the above-mentioned solvent, and the mixing temperature is usually -20 to 150 ° C, preferably -10 ° C.
-100 ° C.

By mixing the raw material chrysanthemic acid and the optically active organic amine in a solvent, a diastereomer salt of the chrysanthemic acid and the optically active organic amine is formed. The diastereomer salt can be taken out by filtering the reaction solution containing the precipitated diastereomer salt as it is. Alternatively, the diastereomer salt may be taken out by cooling the reaction solution to further crystallize the diastereomer salt, and then performing a filtration treatment. Further, the reaction solution is once heated to dissolve part or all of the precipitated diastereomer salt, and then cooled, whereby a diastereomer salt having higher optical purity can be obtained.

The resulting diastereomer salt is treated with an aqueous acid solution such as hydrochloric acid, sulfuric acid or the like, subjected to acid decomposition treatment, and extracted with a water-insoluble organic solvent to contain optically active chrysanthemic acid. An organic layer and an aqueous layer containing an optically active organic amine are obtained. By concentrating the organic layer, optically active chrysanthemic acid can be taken out. Examples of the organic solvent insoluble in water include aromatic hydrocarbon solvents such as toluene and xylene, and aliphatic hydrocarbon solvents such as hexane and heptane. Such water-insoluble organic solvents are:
It may be added in advance during the acid decomposition treatment. The aqueous layer obtained by the above-mentioned extraction treatment is subjected to an alkali treatment, and then subjected to extraction treatment with an unnecessary organic solvent in water to obtain an organic layer containing an optically active organic amine. Can be reused as it is or after concentration treatment as an optical resolving agent.

The resulting diastereomer salt is treated with an aqueous alkali solution such as an aqueous sodium hydroxide solution to carry out alkali decomposition treatment and extraction with an organic solvent insoluble in water, thereby obtaining an optically active organic amine. And an aqueous layer containing optically active chrysanthemic acid. The obtained aqueous layer is subjected to an acid treatment and an extraction treatment with an organic solvent insoluble in water to obtain an organic layer containing an optically active chrysanthemic acid. Acid can be removed. The organic layer containing the optically active organic amine can be reused as an optical resolving agent as it is or after concentration.

The starting chrysanthemic acid is prepared by, for example, adding 2,5-dimethyl-2,4-hexadiene and a compound of the formula (3) in the presence of an asymmetric metal complex catalyst. (Wherein R ⁶ represents an alkyl group) (hereinafter, diazoacetates (3)
Abbreviated. ) To give chrysanthemic acid esters, which can be prepared by subjecting these chrysanthemic esters to alkali decomposition or acid decomposition.

In the formula of diazoacetic acid esters (3), examples of the alkyl group include methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl and n-pentyl. And a linear, branched or cyclic alkyl group having 1 to 6 carbon atoms such as a group, n-hexyl group, cyclopentyl group and cyclohexyl group.

Examples of such diazoacetates (3) include methyl diazoacetate, ethyl diazoacetate, n-propyl diazoacetate, isopropyl diazoacetate, n-butyl diazoacetate, cyclohexyl diazoacetate and the like.

Examples of the asymmetric metal complex include, for example, an asymmetric copper complex, an asymmetric cobalt complex, an asymmetric ruthenium complex, an asymmetric rhodium complex, an asymmetric palladium complex and the like, which comprises a metal and an optically active ligand. A metal complex is mentioned, and an asymmetric copper complex is preferable.

Such an asymmetric metal complex is prepared, for example, by reacting a metal compound with an optically active ligand. As the metal compound, for example, cobalt acetate, copper acetate, rhodium acetate, ruthenium acetate, palladium acetate,
Carboxylic acid metal salts such as copper naphthenate, for example, sulfonic acid metal salts such as copper trifluoromethanesulfonate, for example, cobalt chloride, cobalt bromide, copper chloride, ruthenium chloride,
Metal halides such as rhodium chloride and palladium chloride are exemplified. Examples of the optically active ligand include an optically active bisoxazoline compound, an optically active salicylideneamino alcohol compound, an optically active ethylenediamine compound, an optically active semicholine compound, an optically active camphor compound and the like. Among the optically active ligands, an optically active bisoxazoline compound, an optically active salicylideneamino alcohol compound, and an optically active ethylenediamine compound are preferred.

Examples of the optically active bisoxazoline compound include compounds represented by the following general formula (4) (Wherein R ⁸ and R ⁹ are different from each other and represent a hydrogen atom, an alkyl group, a cycloalkyl group, an optionally substituted phenyl group or an optionally substituted benzyl group,
R ¹⁰ and R ¹¹ are each the same or different, a hydrogen atom, an alkyl group, an optionally substituted phenyl group or an optionally substituted aralkyl group, R ¹²
Represents a hydrogen atom or an alkyl group. Here, R ¹⁰ and R ¹¹ may be bonded to form a ring structure together with the bonded carbon atoms. * Represents an asymmetric carbon atom. ) (Hereinafter abbreviated as optically active bisoxazoline compound (4)).

In the formula of the optically active bisoxazoline compound (4), examples of the alkyl group include the same as those described above.

Examples of the cycloalkyl group include a cyclopentyl group and a cyclohexyl group. Examples of the optionally substituted phenyl group include, in addition to an unsubstituted phenyl group, for example, 2-methyl substituted with a substituent such as the above-mentioned alkyl group, the above-mentioned alkoxy group, the above-mentioned halogen atom, and nitro group. Examples include a phenyl group, a 3-methylphenyl group, a 4-methylphenyl group, a 2-methoxyphenyl group, a 3-methoxyphenyl group, a 4-methoxyphenyl group, a 4-fluorophenyl group, and a 4-nitrophenyl group.

Examples of the optionally substituted benzyl group include, in addition to an unsubstituted benzyl group, the above-mentioned alkyl group, the above-mentioned alkoxy group, the above-mentioned halogen atom,
For example, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 4-methoxybenzyl substituted with a substituent such as nitro Examples include a fluorobenzyl group and a 4-nitrobenzyl group. As the aralkyl group which may be substituted, the above-mentioned aralkyl group and such an aralkyl group include, for example, the above-mentioned alkyl group, the above-mentioned alkoxy group, the above-mentioned halogen atom,
Examples include those in which a substituent such as a nitro group is substituted.

When R ¹⁰ and R ¹¹ are combined with each other to form a ring structure together with the bonding carbon atom, examples of the ring structure include a cyclopentane ring, a cyclohexane ring, and a cycloheptane ring.

Examples of the optically active bisoxazoline compound (4) include, for example, 2,2′-methylenebis [(4
R) -4-Phenyl-2-oxazoline], 2,2′-
Methylenebis [(4R) -4-isopropyl-2-oxazoline], 2,2′-methylenebis [(4R) -4-
tert-butyl-2-oxazoline], 2,2′-methylenebis [(4R) -4-isobutyl-2-oxazoline], 2,2′-methylenebis [(4R) -4-benzyl-2-oxazoline], , 2'-methylenebis [(4R, 5S) -4,5-diphenyl-2-oxazoline], 2,2'-methylenebis [(4R) -4-phenyl-5,5-dimethyl-2-oxazoline], ,
2'-methylenebis [(4R) -4-phenyl-5,5
-Diethyl-2-oxazoline], 2,2'-methylenebis [(4R) -4-phenyl-5,5-di (n-propyl) -2-oxazoline], 2,2'-methylenebis [(4R)- 4-phenyl-5,5-diisopropyl-
2-oxazoline], 2,2′-methylenebis [(4
R) -4-phenyl-5,5-dicyclohexyl-2-
Oxazoline], 2,2'-methylenebis [(4R)-
4-phenyl-5,5-diphenyl-2-oxazoline], 2,2′-methylenebis [(4R) -4-phenyl-5,5-di (2-methylphenyl) -2-oxazoline], 2,2 '-Methylenebis [(4R) -4-phenyl-5,5-di (3-methylphenyl) -2-oxazoline], 2,2'-methylenebis [(4R) -4-phenyl-5,5-di ( 4-methylphenyl) -2-oxazoline], 2,2'-methylenebis [(4R) -4-
Phenyl-5,5-di (2-methoxyphenyl) -2-
Oxazoline], 2,2'-methylenebis [(4R)-
4-phenyl-5,5-di (3-methoxyphenyl)-
2-oxazoline], 2,2′-methylenebis [(4
R) -4-phenyl-5,5-di (4-methoxyphenyl) -2-oxazoline],

2,2'-methylenebis [(4R) -4-
Phenyl-2-oxazoline-5-spiro-1′-cyclobutane], 2,2′-methylenebis [(4R) -4-
Phenyl-2-oxazoline-5-spiro-1′-cyclopentane], 2,2′-methylenebis [(4R) -4
-Phenyl-2-oxazoline-5-spiro-1'-cyclohexane], 2,2'-methylenebis [(4R)-
4-phenyl-2-oxazoline-5-spiro-1′-
Cycloheptane], 2,2′-isopropylidenebis [(4R) -4-phenyl-2-oxazoline], 2,
2′-isopropylidenebis [(4R) -4-isopropyl-2-oxazoline], 2,2′-isopropylidenebis [(4R) -4-tert-butyl-2-oxazoline], 2,2′-isopropyl Redidenbis [(4R)
-4-isobutyl-2-oxazoline], 2,2'-isopropylidenebis [(4R) -4-benzyl-2-oxazoline], 2,2'-isopropylidenebis [(4
R, 5S) -4,5-diphenyl-2-oxazoline]
And those having other absolute configuration structures in each of these compounds.

Examples of the optically active salicylideneamino alcohol compound include, for example, those represented by the general formula (5) (Wherein, R ¹³ represents an alkyl group, a cycloalkyl group, an aryl group, or an aralkyl group, wherein the aryl group and the aralkyl group are substituted with an alkyl group, an alkoxy group, an aryloxy group, or an aralkyloxy group. R ¹⁴ represents a hydrogen atom, an alkyl group, a cycloalkyl group, a phenyl group or a benzyl group, wherein the phenyl group and the benzyl group are an alkyl group, an alkoxy group, a cycloalkyloxy group, an aryloxy group or an aralkyl group; May be substituted with an oxy group, or two R ¹⁴ may be bonded to each other to form a ring structure together with the bonded carbon atom, and Z ¹ and Z ² may be the same or different and each represents a hydrogen atom, Halogen atom, nitro group,
Represents an acyl group, an ester group, a cyano group, an alkyl group, an alkoxy group, an aralkyl group or an aryl group. * Represents an asymmetric carbon atom. )) (Hereinafter, abbreviated as optically active salicylidene amino alcohol compound (5)).

In the above formula of the optically active salicylideneamino alcohol compound (5), the alkyl, cycloalkyl, aryl, aralkyl, alkoxy and halogen atoms are the same as those described above. Can be Examples of the cycloalkyloxy group include a cycloalkyloxy group having 5 to 7 carbon atoms such as a cyclopentyloxy group and a cyclohexyloxy group, and an aryloxy group composed of the above-described aryl group and an oxygen atom And the aralkyloxy group includes those composed of the aralkyl group described above and an oxygen atom. Examples of the acyl group include an acetyl group, a propionyl group, and a benzoyl group.
Examples of the ester group include those composed of a carbonyl group and the above-mentioned alkoxy group such as a methoxycarbonyl group and an ethoxycarbonyl group.

When two R ¹⁴ are combined with each other to form a ring structure together with the bonded carbon atom, examples of the ring structure include a cyclohexane ring.

Examples of the optically active salicylidene amino alcohol compound (5) include (R) -N-salicylidene-2-amino-1,1-diphenyl-1-propanol and (R) -N-salicylidene- 2-amino-
1,1-di (2-methoxyphenyl) -1-propanol, (R) -N-salicylidene-2-amino-1,1-
Di (2-isopropoxyphenyl) -1-propanol, (R) -N-salicylidene-2-amino-1,1-
Di (2-butoxy-5-tert-butylphenyl)-
1-propanol, (R) -N-salicylidene-2-amino-1,1-diphenyl-3-phenyl-1-propanol, (R) -N-salicylidene-2-amino-1,
1-di (2-methoxyphenyl) -3-phenyl-1-
Propanol, (R) -N-salicylidene-2-amino-1,1-di (2-isopropoxyphenyl) -3-phenyl-1-propanol, (R) -N-salicylidene-2-amino-1,1 -Di (2-butoxy-5-ter
t-butylphenyl) -3-phenyl-1-propanol, (R) -N-salicylidene-2-amino-1,1-
Di (2-methoxyphenyl) -3-methyl-1-butanol,

(R) -N- (3-fluorosalicylidene) -2-amino-1,1-di (2-butoxy-5-t
tert-butylphenyl) -1-propanol, (R)
-N- (3-fluorosalicylidene) -2-amino-
1,1-di (2-octyloxy-5-tert-butylphenyl) -1-propanol, (R) -N- (3-
(Fluorosalicylidene) -2-amino-1,1-di (2
-Butoxy-5-tert-butylphenyl) -3-phenyl-1-propanol, (R) -N- (3-fluorosalicylidene) -2-amino-1,1-di (2-methoxyphenyl)- 1-propanol, (R) -N- (3
-Fluorosalicylidene) -2-amino-1,1-diphenyl-1-propanol, (R) -N- (3-fluorosalicylidene) -2-amino-1,1-di (2-benzyloxy -5-methylphenyl) -3- (4-isopropoxyphenyl) -1-propanol, (R) -N-
(3-fluorosalicylidene) -2-amino-1,1-
Diphenyl-3-phenyl-1-propanol, (R)
-N- (3-fluorosalicylidene) -2-amino-
1,1-di (2-methoxyphenyl) -3-methyl-1
-Butanol,

(R) -N- (5-nitrosalicylidene)
-2-amino-1,1-diphenyl-1-propanol, (R) -N- (5-nitrosalicylidene) -2-amino-1,1-diphenyl-3-phenyl-1-propanol, (R ) -N- (5-Nitrosalicylidene) -2
-Amino-1,1-di (2-butoxy-5-tert-
Butylphenyl) -3-phenyl-1-propanol,
(R) -N- (5-nitrosalicylidene) -2-amino-1,1-di (2-butoxy-5-tert-butylphenyl) -1-propanol, (R) -N- (5- Nitrosalicylidene) -2-amino-1,1-di (2-benzyloxy-5-methylphenyl) -3- (4-isopropoxyphenyl) -1-propanol, (R) -N-
(5-nitrosalicylidene) -2-amino-1,1-di (2-methoxyphenyl) -1-propanol, (R)
-N- (5-nitrosalicylidene) -2-amino-1,
1-di (2-tert-butyl-4-methylphenyl)
-3-phenyl-1-propanol, (R) -N- (5
-Nitrosalicylidene) -2-amino-1,1-di (4
-Tert-butylphenyl) -1-propanol,
(R) -N- (5-nitrosalicylidene) -2-amino-1,1-di (2-methoxyphenyl) -3-methyl-
1-butanol,

(R) -N- (5-bromosalicylidene)
-2-amino-1,1-diphenyl-1-propanol, (R) -N- (5-bromosalicylidene) -2-amino-1,1-di (2-methoxyphenyl) -1-propanol, (R) -N- (3,5-dibromosalicylidene) -2-amino-1,1-diphenyl-1-propanol, (R) -N- (3,5-dichlorosalicylidene)
-2-amino-1,1-diphenyl-1-propanol, (R) -N- (3-tert-butylsalicylidene) -2-amino-1,1-diphenyl-1-propanol, (R)- N- (3,5-di-tert-butylsalicylidene) -2-amino-1,1-di (2-methoxyphenyl) -1-propanol, (R) -N- (3,5
-Dinitrosalicylidene) -2-amino-1,1-diphenyl-1-propanol, (R) -N- (3-methoxy-5-nitrosalicylidene) -2-amino-1,1-
Examples include diphenyl-1-propanol and the like, and compounds wherein (R)-of these compounds is replaced by (S)-.

Examples of the optically active ethylenediamine compound include compounds represented by the following general formula (6) (Wherein, R ¹⁵ represents a hydrogen atom or an alkyl group;
Represents an integer of 1 to 5. * Represents an asymmetric carbon. ) (Hereinafter, abbreviated as optically active ethylenediamine compound (6)).

In the formula of the optically active ethylenediamine compound (6), examples of the alkyl group include the same as those described above.

Examples of the optically active ethylenediamine compound (6) include bis [N- (2,4,6-trimethylphenyl) methyl]-(1R), (2R) -diphenylethylenediamine, bis [N- (2 , 4,6-trimethylphenyl) methyl]-(1S), (2S) -diphenylethylenediamine and the like.

The amount of the asymmetric metal complex to be used is usually 0.00000 in terms of metal, based on the diazoacetic acid ester (3).
1 to 0.02 mole times, preferably 0.00002 to 0.2 times.
It is 01 mole times.

The reaction between 2,5-dimethyl-2,4-hexadiene and diazoacetates (3) is carried out, for example, by adding a mixture of an asymmetric metal complex and 2,5-dimethyl-2,4-hexadiene to a solvent. It is carried out by adding the dissolved diazoacetates (3). As the solvent,
For example, halogenated hydrocarbon solvents such as chlorobutane, 1,2-dichloroethane, chloroform, and carbon tetrachloride, for example, aliphatic hydrocarbon solvents such as hexane, heptane, and cyclohexane, for example, aromatic hydrocarbons such as benzene, toluene, and xylene A single solvent or a mixed solvent such as an ester solvent such as methyl acetate and ethyl acetate is exemplified. Of course, 2,5-dimethyl-2,4-hexadiene may be used as the solvent. The amount of the solvent used is usually 1 to 50 times by weight based on the diazoacetic acid ester (3),
Preferably it is 5 to 30 times by weight.

The reaction between 2,5-dimethyl-2,4-hexadiene and diazoacetic esters (3) is usually carried out in an atmosphere of an inert gas such as argon gas, nitrogen gas or the like. It is usually -10 to 120C, preferably 0 to 100C.

The amount of 2,5-dimethyl-2,4-hexadiene to be used is generally 1 to 50 mol times, preferably 5 to 30 mol times, relative to the diazoacetates (3).

After completion of the reaction, the obtained reaction solution is subjected to a distillation treatment, whereby chrysanthemic acid esters can be taken out. The extracted chrysanthemic acid ester may be subjected to acid decomposition or alkali decomposition as it is, or may be further purified by ordinary purification means such as rectification or column chromatography and then subjected to acid decomposition or alkali decomposition.

Examples of the acid used for acid decomposition include hydrochloric acid,
Mineral acids such as sulfuric acid can be mentioned, and alkalis used for alkali decomposition include, for example, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide. The amount of the alkali used for the alkali decomposition is usually 1 to 2 times, preferably 1 to 1.5 times the mol of chrysanthemic acid esters.

The chrysanthemic acid ester of the present invention can be prepared by acid- or alkali-decomposition of the obtained chrysanthemic acid ester. The raw chrysanthemic acid may be prepared by mixing the acids. The trans-rich racemic chrysanthemic acid is obtained, for example, by reacting tert-butyl hydroperoxide and aluminum bromide on (−)-cis chrysanthemic acid or a mixture of (−)-trans chrysanthemic acid in a toluene solvent. Can be prepared. The trans-form ratio of racemic chrysanthemic acid which is rich in the trans-form is preferably 80% or more.
5% or more is more preferable.

[0046]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Example 1 Trans-isomer / cis-isomer ratio = 80/20, optical purity of trans-isomer = 7.9% e. e. (Optical purity of cis form = 2
6.8% e. e. 20 g of chrysanthemic acid and 120 g of toluene
, And the mixture was dissolved by stirring, and (S) -1-phenyl-2-
14.8 g of (p-tolyl) ethylamine was added and dissolved by heating. After cooling to room temperature, the precipitated crystals were collected by filtration, washed with toluene, and then dissolved in a 5% by weight aqueous sodium hydroxide solution. Toluene was added and the mixture was extracted, and the resulting aqueous layer was acidified with a 5% by weight aqueous sulfuric acid solution and then extracted with toluene. The toluene was distilled off from the obtained organic layer, and the trans-form / cis-form ratio was 82/18 and the optical purity of the trans-form was 95% e. e. (Optical purity of cis form = 9
8% e. e. 7.5 g of chrysanthemic acid (yield 37.6)
%).

Example 2 Trans / isomer ratio = 79/21, trans isomer optical purity = 3.7% e.g. e. (Optical purity of cis form = 2
1.4% e. e. 180 g of toluene in 30 g of chrysanthemic acid
, And the mixture was dissolved by stirring, and (S) -1-phenyl-2-
21.2 g of (p-tolyl) ethylamine was added and dissolved by heating. After cooling to room temperature, the precipitated crystals were collected by filtration, washed with toluene, and then dissolved in a 5% by weight aqueous sodium hydroxide solution. Toluene was added and the mixture was extracted, and the resulting aqueous layer was acidified with a 5% by weight aqueous sulfuric acid solution and then extracted with toluene. The toluene was distilled off from the obtained organic layer, and the trans-form / cis-form ratio was 82/18 and the optical purity of the trans-form was 95% e. e. (Optical purity of cis form = 9
8% e. e. ) Was obtained (34.3 g) (yield 34.3).
%).

Example 3 1.6 mg of copper acetate monohydrate and (R) -N-salicylidene-2-amino- were placed in a 50 mL Schlenk tube purged with nitrogen.
1,1-di (2-methoxyphenyl) propanol3.
3.6 mg of asymmetric copper complex prepared by reacting with 44 mg
After adding 6 g of 2,5-dimethyl-2,4-hexadiene and 0.86 mg of phenylhydrazine, 1.14 g of ethyl diazoacetate was added dropwise at an internal temperature of 80 ° C. over 2 hours. Then, stirring and holding at the same temperature for 1 hour,
A reaction solution containing chrysanthemic acid ethyl ester was obtained. The amount of produced chrysanthemic acid ethyl ester was determined by gas chromatography to be 1.76 g (yield based on ethyl diazoacetate:
90%), and the trans / cis ratio = 59/41.
Met. Under reduced pressure conditions, unreacted 2,5
After distilling off the dimethyl-2,4-hexadiene, 1 g of the concentrated residue was collected, 10 mL of a 1N aqueous sodium hydroxide solution and 5 mL of ethanol were added, and the internal temperature was 100 mL.
Stirred and maintained at ℃ for 1 hour to obtain chrysanthemic acid. The optical purity of the obtained trans form of chrysanthemic acid is 35% e. e. . The optical purity of the cis form is 35% e. e. (Chrysanthemic acid was reacted with 1-menthol to convert to diastereomeric ester and analyzed by gas chromatography).

The remaining concentrated residue is similarly alkali-decomposed with an aqueous sodium hydroxide solution, and the resulting chrysanthemic acid and trans-form racemic chrysanthemic acid (trans-form / cis-form ratio = 95/5)
Were mixed at a weight ratio of 53/57, a trans / cis ratio = 81/19, and an optical purity of the trans isomer = 9.6% e.
e. Chrysanthemic acid (optical purity of cis isomer = 31% ee) was prepared. 110 g of toluene was added to 18.3 g of the prepared chrysanthemic acid.
And dissolved by stirring. Then, (S) -1-phenyl-2
14.4 g of-(p-tolyl) ethylamine was added and dissolved by heating. After cooling to room temperature, the precipitated crystals were collected by filtration, washed with toluene, and dissolved in a 5% by weight aqueous sodium thorium hydroxide solution. Extraction treatment with toluene, the resulting aqueous layer was
After acidification with 5% by weight sulfuric acid aqueous solution, the mixture was extracted with toluene. Toluene was distilled off from the obtained organic layer, and the trans-form / cis-form ratio was 83/27 and the optical purity of the trans-form was =
91% e. e. (Optical purity of cis form = 91% ee)
There was obtained 7.33 g of chrysanthemic acid. Yield: 40.1%.

Example 4 In a 50 mL Schlenk tube purged with nitrogen, 0.70 mg of copper acetate monohydrate and (R)-[5-nitro-N-salicylidene] -2-amino-1,1-di (2- 1.74 mg of an asymmetric copper complex prepared by reacting 1.53 mg of (methoxyphenyl) propanol with 2,5-dimethyl-2,
6 g of 4-hexadiene was added, and phenylhydrazine 0.1 g was added.
After adding 5 mg, 1.14 g of ethyl diazoacetate was added dropwise at an internal temperature of 80 ° C. over 2 hours. Thereafter, the mixture was stirred and maintained at the same temperature for 1 hour to obtain a reaction solution containing ethyl chrysanthenate. The amount of produced chrysanthemic acid ethyl ester was determined by gas chromatography to be 1.89 g (yield based on ethyl diazoacetate: 96.5%), and the trans / cis ratio was 59/41. Under reduced pressure conditions,
After unreacted 2,5-dimethyl-2,4-hexadiene was distilled off from the reaction solution, 1 g of the concentrated residue was fractionated, and 10 mL of a 1N aqueous sodium hydroxide solution and ethanol were added.
Then, the mixture was stirred and maintained at an internal temperature of 100 ° C. for 1 hour to obtain chrysanthemic acid. The optical purity of the obtained trans form of chrysanthemic acid is 35% e. e. . The optical purity of the cis form is 35% e.
e. (Chrysanthemic acid was reacted with 1-menthol to form a diastereomer ester and analyzed by gas chromatography).

The remaining concentrated residue is similarly alkali-decomposed with an aqueous sodium hydroxide solution, and the obtained chrysanthemic acid and trans-form of racemic chrysanthemic acid (trans-form / cis-form ratio = 95/5)
Were mixed at a weight ratio of 53/57, a trans / cis ratio = 81/19, and an optical purity of the trans isomer = 9.6% e.
e. Chrysanthemic acid (optical purity of cis isomer = 31% ee) was prepared. 110 g of toluene was added to 18.3 g of the prepared chrysanthemic acid.
And dissolved by stirring. Then, (S) -1-phenyl-2
14.4 g of-(p-tolyl) ethylamine was added and dissolved by heating. After cooling to room temperature, the precipitated crystals were collected by filtration, washed with toluene, and dissolved in a 5% by weight aqueous sodium thorium hydroxide solution. Extraction treatment with toluene, the resulting aqueous layer was
After acidification with 5% by weight sulfuric acid aqueous solution, the mixture was extracted with toluene. Toluene was distilled off from the obtained organic layer, and the trans-form / cis-form ratio was 83/27 and the optical purity of the trans-form was =
91% e. e. (Optical purity of cis form = 91% ee)
There was obtained 7.33 g of chrysanthemic acid. Yield: 40.1%.

Comparative Example 1 Racemic chrysanthemic acid (trans / cis isomer ratio = 75/25) 1
After adding 390 g of toluene to 00 g and stirring and dissolving, 47.0 g of (S) -1-phenyl-2- (p-tolyl) ethylamine was added and dissolved by heating. After cooling to room temperature, the precipitated crystals were collected by filtration, washed with toluene, dissolved in a 5% by weight aqueous sodium hydroxide solution, and extracted with toluene. The obtained aqueous layer was acidified with 5% by weight sulfuric acid aqueous solution and extracted with toluene. Toluene was distilled off from the obtained organic layer, and the ratio of trans-form / cis-form was 80 /.
20, optical purity of trans form = 96% e. e. 20.8 g of chrysanthemic acid (optical purity of cis-isomer = 98% ee) was obtained. Yield: 20.8%.

Comparative Example 2 Racemic chrysanthemic acid (trans / cis ratio = 79/21) 1
To 6.3 g, 65 g of toluene was added, stirred and dissolved, and then (S) -α- (1-naphthyl) ethylamine.
0 g and 1.3 g of water were added and dissolved by heating. After cooling to room temperature, the precipitated crystals were collected by filtration, washed with toluene, dissolved in a 5% by weight aqueous sodium hydroxide solution, and extracted with toluene. The obtained aqueous layer was acidified with 5% by weight sulfuric acid aqueous solution, and extracted with toluene. Toluene was distilled off from the obtained organic layer, and the trans / cis ratio was 98%.
/ 2, optical purity of trans form = 97% e. e. 4.1 g of chrysanthemic acid (optical purity of cis form = 73% ee) was obtained.
Yield: 25.3%.

Example 5 Trans-isomer / cis-isomer ratio = 78/22, optical purity of trans-isomer = 2.7% e.g. e. (Optical purity of cis isomer = 1)
7.6% e. e. ) Of chrysanthemic acid in 143 g of toluene 502
g, and dissolved by stirring.
95.4 g of (p-tolyl) ethylamine was added and dissolved by heating. After cooling to room temperature, the precipitated crystals were collected by filtration, washed with toluene, and then dissolved in a 5% by weight aqueous sodium hydroxide solution. Toluene was added and the mixture was extracted, and the obtained aqueous layer was acidified with 5% by weight sulfuric acid aqueous solution and then extracted with toluene. Toluene was distilled off from the obtained organic layer, and the trans-form / cis-form ratio was 81/19 and the optical purity of the trans-form was 95% e. e. (Optical purity of cis form = 9
7% e. e. ) Was obtained (yield 33.6).
%).

[0056]

According to the present invention, the optical purity of the trans isomer, which can be relatively easily prepared, is 2 to 10% e. e. By using a chrysantic acid having a trans-form ratio of less than 70% as a raw material and performing optical resolution, a chrysantic acid having a high optical purity can be obtained.
Since it can be obtained efficiently and with good yield, it is industrially advantageous.

Claims (11)

[Claims] 1. A trans-isomer ratio of 70% or more and a trans-isomer optical purity of 2 to 10% e. e. A process for producing optically active chrysanthemic acid, comprising the step of reacting chrysanthemic acid with an optically active organic amine on said chrysanthemic acid to optically resolve said chrysanthemic acid. 2. An optically active organic amine having the general formula (1) (Wherein, R ¹ and R ² are the same or different and each represents a hydrogen atom, an alkyl group or an aralkyl group. Here, the aralkyl group may be substituted with a hydroxyl group, an alkyl group or an alkoxy group. X and Y are the same or different and each represent a hydrogen atom, a halogen atom, an alkyl group or an alkoxy group; * represents an asymmetric carbon atom); ) (Wherein, R ¹ and R ² have the same meanings as described above;
³ represents an alkyl group. R ⁴ and R ⁵ each represent a hydrogen atom, or R ⁴ and R ⁵ combine to form a benzene ring together with the bonded carbon atoms. * Represents an asymmetric carbon atom. The method for producing optically active chrysanthemic acid according to claim 1, which is an optically active organic amine represented by the formula: 3. Chrysanthemic acid has a trans-form ratio of 75 to 98%.
And the trans optical purity is 2.5 to 10% e.
e. The method for producing optically active chrysanthemic acid according to claim 1, wherein the amount is less than 2. 4. The trans-isomer ratio is 70% or more and the trans-isomer optical purity is 2 to 10% e. e. Is less than 2,5-dimethyl- in the presence of an asymmetric metal complex catalyst.
2,4-hexadiene and general formula (3) (Wherein, R ⁶ represents an alkyl group) to obtain a chrysanthemic acid ester,
The process for producing optically active chrysanthemic acid according to claim 1, which is chrysanthemum acid obtained by subjecting said chrysanthemic acid ester to alkali decomposition or acid decomposition. 5. A trans-form ratio of 70% or more and a trans-form optical purity of 2 to 10% e.g. e. Is less than 2,5-dimethyl- in the presence of an asymmetric metal complex catalyst.
2,4-hexadiene and general formula (3) (Wherein, R ⁶ represents an alkyl group) to obtain a chrysanthemic acid ester,
2. The method for producing optically active chrysanthemic acid according to claim 1, wherein chrysanthemum acid obtained by subjecting the chrysanthemic acid esters to alkali decomposition or acid decomposition is mixed with racemic chrysanthemic acid rich in trans form. 6. The optically active metal complex according to claim 4, wherein the asymmetric metal complex is a copper, cobalt, rhodium, ruthenium or palladium metal and an optically active ligand. Production method of chrysanthemic acid. 7. The method for producing optically active chrysanthemic acid according to claim 4, wherein the asymmetric metal complex is an asymmetric copper complex comprising copper and an optically active ligand. 8. The optically active ligand according to claim 6, wherein the optically active ligand is an optically active bisoxazoline compound, an optically active salicylideneamino alcohol compound or an optically active ethylenediamine compound. Production method of chrysanthemic acid 9. An optically active bisoxazoline compound represented by the general formula (4): (Wherein R ⁸ and R ⁹ are different from each other and represent a hydrogen atom, an alkyl group, a cycloalkyl group, an optionally substituted phenyl group or an optionally substituted benzyl group,
R ¹⁰ and R ¹¹ are each the same or different, a hydrogen atom, an alkyl group, an optionally substituted phenyl group or an optionally substituted aralkyl group, R ¹²
Represents a hydrogen atom or an alkyl group. Here, R ¹⁰ and R ¹¹ may be bonded to form a ring structure together with the bonded carbon atoms. * Represents an asymmetric carbon atom. 9. The method for producing optically active chrysanthemic acid according to claim 8, which is an optically active bisoxazoline compound represented by the formula: 10. An optically active salicylideneamino alcohol compound represented by the general formula (5): (Wherein, R ¹³ represents an alkyl group, a cycloalkyl group, an aryl group, or an aralkyl group, wherein the aryl group and the aralkyl group are substituted with an alkyl group, an alkoxy group, an aryloxy group, or an aralkyloxy group. R ¹⁴ represents a hydrogen atom, an alkyl group, a cycloalkyl group, a phenyl group or a benzyl group, wherein the phenyl group and the benzyl group are an alkyl group, an alkoxy group, a cycloalkyloxy group, an aryloxy group or an aralkyl group; May be substituted with an oxy group, or two R ¹⁴ may be bonded to each other to form a ring structure together with the bonded carbon atom, and Z ¹ and Z ² may be the same or different and each represents a hydrogen atom, Halogen atom, nitro group,
Represents an acyl group, an ester group, a cyano group, an alkyl group, an alkoxy group, an aralkyl group or an aryl group. * Represents an asymmetric carbon atom. The method for producing optically active chrysanthemic acid according to claim 8, which is an optically active salicylideneamino alcohol compound represented by the formula: 11. An optically active ethylenediamine compound,
General formula (6) (Wherein, R ¹⁵ represents a hydrogen atom or an alkyl group;
Represents an integer of 1 to 5. * Represents an asymmetric carbon atom. The method for producing optically active chrysanthemic acid according to claim 8, which is an optically active ethylenediamine compound represented by the formula: