JP2000103788A - Production of optically active epihalohydrin - Google Patents

Abstract

PROBLEM TO BE SOLVED: To simply obtain an optically active epihalohydrin useful as a synthetic raw material for medicines, a medicine intermediate, or the like, under mild conditions through one stage reaction by hydrolyzing a racemic isomer of an epihalohydrin in the presence of an optically active transition metal complex catalyst and separating a specific optically active alcohol produced as a by- product. SOLUTION: A racemic isomer of an epihalohydrin such as epichlorohydrin is hydrolyzed, preferably in the presence of an optically active transition metal complex catalyst which is a complex of the formula [R1 and R2 are each H or the like; R3 to R5 are each H or the like; R6 is a group of the formula R7-CO or the like; R7 is a (substituted)alkyl or the like], preferably at -60 to 30 deg.C, usually for about 1 min to 10 days and the produced optically active 3-halo-1,2- propanediol is separated to provide the objective compound. The catalyst is obtained by subjecting, e.g. N,N-bis[2-(mesitoy)-3-oxobutylidene]-(1S,2S)-1,2- diphenylethylenediaminatocobalt (II) to air oxidation in the presence of acetic acid.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a method for producing an optically active epihalohydrin. Optically active epihalohydrin is used as a raw material for synthesizing various medicaments, pharmaceutical intermediates and agricultural chemicals having optical activity.

[0002]

2. Description of the Related Art Epihalohydrin has the following general formula:

[0003]

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A compound represented by the formula (X represents a halogen atom), and the optically active substance is a functional compound such as a medicine, a pharmaceutical intermediate, an agricultural chemical, other physiologically active substances, and a ferroelectric liquid crystal material. It is useful as a raw material for synthesizing fine chemicals. Conventionally, regarding the production of optically active epihalohydrin, a method utilizing an asymmetric source derived from D-mannitol as a synthetic chemistry technique (J. Org. Che).
m. , 43, 4876 (1978). ), A method of synthesizing from optically active glycerol 1,2-acetonide (JP-A-1-193262) and the like. As a biochemical method using an enzyme, a method of inducing lipase on (±) -1-acetoxy-2,3-dichloropropane followed by induction (Agric. Biol. Ch.
em. 46 1593 (1982)) and an optically active 2,3-dichloro-1-propanol obtained by an enzymatic method (JP-A-61-132196, JP-A-3-1196).
80197) with an alkali under atmospheric pressure or reduced pressure (JP-A-62-6697, JP-A-3-180196, JP-A-6-211).
No. 822) has been used. However, all of these methods have disadvantages such as the use of expensive reagents or the complicated and complicated production steps.

[0005] In addition, from the racemic epihalohydrin, 1
In the step, as a method for obtaining an optically active form of this compound,
A method using a microorganism having an asymmetric hydrolysis ability of an epoxide (Japanese Patent Application Laid-Open No. Hei 6-261178) and a method using an asymmetric hydrolysis using an optically active metal compound (Sc)
issue, 277 936 (1997)). However, the former has disadvantages such as low productivity, and the latter has an inadequate activity using expensive reagents.

[0006]

An object of the present invention is to provide a method for producing a desired optically active epihalohydrin from a racemic epihalohydrin in a one-step reaction.

[0007]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, when an optically active transition metal complex catalyst is used, racemic epihalohydrin can be obtained.
It has been found that only one of the R-form or the S-form is preferentially hydrolyzed to be optically active 3-halo-1,2-propanediol, and that the other optically active epihalohydrin can be easily obtained as an unreacted substance, The present invention has been achieved.
That is, the gist of the present invention is to hydrolyze a racemic epihalohydrin in the presence of an optically active transition metal complex catalyst,
A method for producing an optically active epihalohydrin, comprising separating the generated optically active 3-halo-1,2-propanediol.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, a method for producing an optically active epihalohydrin of the present invention will be described in detail. As a raw material of the method of the present invention, any epihalohydrin such as epichlorohydrin and epibromohydrin can be used. The optically active metal compound used as the catalyst is not particularly limited, for example, chromium, aluminum,
Representative examples include complexes of at least one transition metal selected from copper, titanium, vanadium, manganese, iron, cobalt, zinc, nickel, ruthenium, rhodium, hafnium and zirconium. Among these, complexes of at least one transition metal selected from chromium, aluminum, copper, titanium, vanadium, manganese, iron, cobalt, nickel, and ruthenium include, for example, an optically active chromium (III) complex and an optically active Aluminum (III) complex, optically active copper (II) complex, optically active titanium (IV) complex, optically active iron (III) complex, optically active ruthenium (III) complex, optically active oxovanadium (IV)
Complex, optically active manganese (III) complex, optically active cobalt
(III) complexes and optically active cobalt (II) complexes, etc., preferably optically active cobalt (III) complexes. In particular, the optically active cobalt (II) represented by the following general formula (a)
I) It is preferable to use a complex since an optically active epihalohydrin can be obtained with a high optical yield.

[0009]

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(Wherein R¹And R^TwoAre different,
A hydrogen atom, an alkyl group which may have a substituent or
Represents an aryl group. Also, two R¹Two or two
R^TwoAnd each other may combine with each other to form a ring.
R^Three, R^FourAnd R^FiveMay be the same or different, and water
A hydrogen atom, an alkyl group which may have a substituent or
An aryl group, an acyl group or an alkoxycarbonyl group
Show. Also, R^ThreeAnd R ^Four, R^FourAnd R^FiveAre joined to each other
To form a ring. Where R^FourAnd R^FiveAre combined
It does not form a benzene ring. R⁶Is R⁷-CO
-Or R⁸-SO_Two-Group (R⁷And R⁸Respectively
An alkyl group or an aryl group which may have a substituent
Is shown. ). )

In the general formula (a), R ¹ and R ² are different groups, each being a hydrogen atom, an alkyl group or an aryl group which may have a substituent. As the alkyl group, an alkyl group having 1 to 20 carbon atoms, specifically, a methyl group, an ethyl group, an n-propyl group, an i-propyl group,
n-butyl group, sec-butyl group, t-butyl group, n-
Pentyl group, n-heptyl group, n-octyl group, 1-methylbutyl group, 2-methylbutyl group, 3-methylbutyl group, 1-methylpentyl group, 2-methylpentyl group, 3
-Methylpentyl group, 4-methylpentyl group, 1-methylheptyl group, 2-methylheptyl group, 3-methylheptyl group, 4-methylheptyl group, 5-methylheptyl group, and the like, preferably having 3 carbon atoms. A branched alkyl group having from 16 to 16 carbon atoms, and more preferably an α-position carbon atom having 4 to 12 carbon atoms is a tertiary branched alkyl group. Further, these alkyl groups may have an alkoxy group, a halogen atom, an alkoxycarbonyl group, or the like as a substituent, and specifically, for example, a 2-methoxyethyl group, a 2-ethoxyethyl group, a 2-chloroethyl group , A 2-fluoroethyl group,
Examples thereof include a 2-ethoxycarbonylethyl group, a 3-methoxypropyl group, a 3-ethoxypropyl group, a 3-chloropropyl group, a 3-fluoropropyl group, and a 3-ethoxycarbonylpropyl group. As the aryl group, an alkoxy group as a substituent having 6 to 25 carbon atoms, preferably 6 to 14 carbon atoms, an aryl group which may have a halogen atom or the like,
Specifically, a phenyl group, a 4-methylphenyl group,
Methylphenyl group, 2-methylphenyl group, 4-ethylphenyl group, 3-ethylphenyl group, 2-ethylphenyl group, 4-methoxyphenyl group, 3-methoxyphenyl group, 2-methoxyphenyl group, 4-chlorophenyl group ,
3-chlorophenyl group, 2-chlorophenyl group, 4-fluorophenyl group, 3-fluorophenyl group, 2-fluorophenyl group, 3,5-dimethylphenyl group, 2,4
-Dimethylphenyl group, 2,3-dimethylphenyl group,
3,5-dimethoxyphenyl group, 2,4-dimethoxyphenyl group, 3,5-diethylphenyl group, 2,4-diethylphenyl group, 2,3-diethylphenyl group, 4-t
-Butyl-2-methylphenyl group, 3,5-dichlorophenyl group, 2,4-dichlorophenyl group, 3,5-difluorophenyl group, 2,4-difluorophenyl group, 1
-Naphthyl group, 2-naphthyl group, 2,4,6-trimethylphenyl group and the like. Further, two R ^{1 s} or two R ^{2 s} may be bonded to each other to form a ring, for example, an alkylene group such as-(CH ₂ ) _4- to form a And the like may be formed. R ¹ and R ²
It is preferable that one of them is an aryl group and the other is a hydrogen atom. It is particularly preferred that the other aryl group is a hydrogen atom.

R^Three, R^FourAnd R^FiveAre the same but different
A hydrogen atom, a linear or branched alkyl group
Or an aryl group, an acyl group, or an alkoxycarbo
And it may have a substituent. Alkyl group
And the aryl group is R ¹, R^TwoThe same as
Alkyl groups and aryl groups which may have a substituent
I can do it. As the acyl group, formyl group, acetyl
Group, perfluoroacetyl group, propionyl group, butyric
Group, isobutyryl group, valeryl group, isovaleryl group,
Pivaloyl, lauroyl, myristoyl, palmi
Toyl, stearoyl, acryloyl, propio
Loyl group, methacryloyl group, crotonoyl group, benzo
Yl group, mesitoyl group, 1-naphthoyl group, 2-naphtho
Il group, 2-toluoyl group, 3-toluoyl group, 4-to
Oleoyl group, 3,5-xytoyl group, 2,4-xytoyl
Group, 2,3-xytoyl group, 4-anisoyl group, 3-
Anisoyl group, 2-anisoyl group, vanilloyl group, pive
Ronioil group, 4-t-butyl-2-toluoyl group, 9
-Anthroyl group, 3-anthroyl group and the like are typical.
You. Representative examples of alkoxycarbonyl groups include methoxy
Cicarbonyl group, ethoxycarbonyl group, propoxyca
Rubonyl group, butoxycarbonyl group, pentyloxyca
Rubonyl group, hexyloxycarbonyl group, octylio
Xycarbonyl group, cyclopentyloxycarbonyl
Group, cyclohexyloxycarbonyl group, cyclooctyl
Ruoxycarbonyl group, phenoxy group, benzyloxy
Carbonyl group, 3-menthyloxycarbonyl group, 2-
Menthyloxycarbonyl group, 2-bornyloxycar
Bonyl group, 2-norbornyloxycarbonyl group, 3-
Pinanyloxycarbonyl group, 4-pinanyloxycar
And a bonyl group.

Further, R ³ and R ⁴ or R ⁴ and R ⁵ may be bonded to each other to form a ring.
It may be an alkylene group such as H ₂ ) ₄ — to form a ring such as a 6-membered ring. However, R ⁴ and R ⁵ do not combine to form a benzene ring. Preferably, R ³ is a hydrogen atom or an alkyl group having 1 to 5 carbon atoms, and R ⁴ is a mesitoyl group, 1-naphthoyl group, 2-naphthoyl group,
A 9-anthroyl group, and R ³ has 1 to 1 carbon atoms.
6 alkyl groups. Particularly preferably, R ³ is a hydrogen atom, R ⁴ is a mesytoyl group and R ⁵ is a methyl group.

R ⁶ is R ⁷ —CO— or R ⁸ —SO ₂
R ⁷ and R ⁸ each represent a hydrogen atom or a carbon atom having 1 to 2 carbon atoms which may have a substituent.
And represents an alkyl group having 0 or an aryl group having 6 to 25 carbon atoms. Specific examples of the alkyl group or aryl group which may have a substituent include the same alkyl group or aryl group as in R ¹ and R ² . Specific examples of R ⁶ include, for example, formyl group, acetyl group, monochloroacetyl group, monofluoroacetyl group, trifluoroacetyl group, propionyl group, 3,3,3-trifluoropropionyl group, n-butyryl group, isobutyryl group , Valeryl group, isovaleryl group, benzoyl group, o-, m-,
acyl groups such as p-fluorobenzoyl group, o-, m-, p-trifluoromethylbenzoyl group, methanesulfonyl group, ethanesulfonyl group, benzenesulfonyl group, p
-A toluenesulfonyl group, a fluoromethanesulfonyl group and the like. Preferred are an acetyl group, a monofluoroacetyl group, a trifluoroacetyl group, a methanesulfonyl group and a fluoromethanesulfonyl group, and particularly preferred is a trifluoroacetyl group.

Optically active cobalt represented by the general formula (a)
(III) The complex is a novel complex, for example, air-oxidizing an optically active cobalt (II) complex represented by the general formula (b) corresponding to the general formula (a) in the presence of an organic acid. Can be manufactured more easily.

[0016]

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(In the formula, R ^{1 to} R ⁵ have the same meaning as in the general formula (a).) The optically active cobalt (II) complex represented by the general formula (b) is described in, for example, JP-A-9-151143. Can be prepared according to the method described in Japanese Patent Application Publication No. Further, since a part of the complex represented by the general formula (b) is commercially available, a commercial product can be used. When producing the complex of the general formula (a) from the complex of the general formula (b), the organic acid used is a carboxylic acid or a sulfonic acid corresponding to R ⁶ , for example, acetic acid,
Monochloroacetic acid, formic acid, monofluoroacetic acid, trifluoroacetic acid, propionic acid, n-butanoic acid, isobutanoic acid,
Examples include pentanoic acid, isopentanoic acid, and benzoic acid. Examples of the sulfonic acid include methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid, and trifluoromethanesulfonic acid. The amount of the organic acid to be used is selected in the range of 1 to 10 times, preferably 1 to 3 times the mole of the optically active cobalt (II) complex represented by the general formula (b). As an example of a typical production method, the complex of the general formula (b) may be dissolved in an appropriate solvent, and the above-mentioned organic acid may be mixed under conditions that allow contact with air. After completion of the reaction, the complex of the general formula (a) can be easily isolated by a known method such as distillation, crystallization, or column separation.

The solvent used is not particularly limited as long as it dissolves the complex of the general formula (b) and does not react with (b). The reaction temperature is selected from the range of 0 to 150C, preferably 10 to 80C. The reaction time varies depending on (b) used and the reaction temperature and cannot be specified unconditionally, but is usually in the range of 1 to 6 hours. The oxidation may be performed while air or molecular oxygen is passed through the reaction solution. Optically active cobalt represented by the general formula (a)
(III) Examples of the complex are shown below, but the complex used in the present invention is not limited to these.

[0019]

[Table 1]

According to the method of the present invention, when the racemic epihalohydrin is hydrolyzed in the presence of an optically active transition metal complex catalyst, the amount of the catalyst used is 0.1 × 10 4 with respect to 1 mol of the raw material racemic epihalohydrin. ^-6 to 1 mol, preferably 0.1 x 10 ^{-4 to} 0.1 mol. After completion of the reaction, the catalyst is distilled of the reaction product and the solvent,
It is separated by a general method such as extraction and can be used repeatedly. In addition, the hydrolysis is carried out in the presence of water in the reaction system, and the amount of water used is 0.1 to 10 mol, preferably 0.5 to 5 mol, per mol of the racemic epihalohydrin as the raw material. Range. If the amount of water is less than 0.1 mole times, the conversion of the raw material is not sufficient and
If it is more than 0 mole times, the desired optically active epihalohydrin tends to be hydrolyzed, which is not preferable. The history of water used does not greatly affect the reaction, but distilled water and ion-exchanged water are preferred.

The hydrolysis reaction of epihalohydrin according to the method of the present invention can be carried out without using any solvent. However, when the catalyst used is hardly soluble in the starting racemic epihalohydrin, it is used for dissolving it. Can be carried out in a suitable solvent as required. Examples of these solvents include hydrocarbons such as hexane, benzene, and toluene; ethers such as diethyl ether, dimethoxyethane, tetrahydrofuran, and dioxane;
Esters such as ethyl acetate, butyl acetate and butyrolactone can be exemplified. The use amount of these solvents is not particularly limited. In the method of the present invention, for the purpose of further increasing the selectivity, it is possible to add an appropriate additional substance and carry out the method. Examples of the additive include optically active carboxylic acids, and such carboxylic acids include D and L.
-Tartaric acid, D or L-malic acid, D or L-mandelic acid and the like. The amount of these additives to be used is in the range of 0.1 to 10 times, preferably 0.5 to 5 times the mole of the catalyst.

The reaction temperature is usually preferably in the range of -100 to 80 ° C, more preferably in the range of -80 to 50 ° C, and particularly preferably in the range of -60 to 30 ° C. As for the reaction pressure, normal pressure is sufficient as long as the solvent does not evaporate.
The reaction time is usually about 1 minute to 10 days. Further, a sample of the reaction mixture is sequentially collected and analyzed by thin-layer chromatography, gas chromatography, liquid chromatography, or the like, so that the progress of the reaction can be confirmed.

After the reaction, the by-product optically active alcohol is separated from the obtained reaction mixture to obtain the desired optically active epihalohydrin. Separation and purification of by-products or purification of optically active epihalohydrin can be performed by a known method,
For example, it can be performed by a combination of methods such as distillation, adsorption, extraction, and recrystallization. In the production method of the present invention, any optically active epihalohydrin can be obtained by selecting an optically active metal complex to be used as a catalyst. Further, as a by-product, 3-halo-1,2-propanediol having an optical activity different from the intended optically active epihalohydrin can be obtained.

[0024]

EXAMPLES The present invention will be described in more detail with reference to the following examples, which should not be construed as limiting the scope of the invention. The product was quantitatively analyzed by gas chromatography using an internal standard method using octane as an internal standard substance, and the yield was determined by the following formulas (1) and (2). The selectivity of the R-form and the S-form of epihalohydrin and 3-halo-1,2-propanediol was analyzed by high performance liquid chromatography (optically active column: CHIRALPAK AD, manufactured by Daicel), and the following formula (3) , (4).

[0025]

(Equation 1)

In the above formula, EHH means epihalohydrin, and HPD means 3-halo-1,2-propanediol. Example 1 N, N'-bis [2-
(Mesitoyl) -3-oxobutylidene]-(1S, 2
S) -1,2-Diphenylethylenediaminatocobalt (II) 35 mg (0.05 mmol), acetic acid 6 μl
(0.1 mmol), and 3 ml of toluene as a solvent were charged, the system was filled with air, stirred at 25 ° C. for 1 hour using a stirrer, the solvent was removed under reduced pressure, and the mixture was dried. . 38 mg of cobalt (III) complex shown in 1
(0.05 mmol) was obtained. Under ice-cooling, 930 mg (10 mmol) of racemic epichlorohydrin and 600 mg (33.3 mmol) of water were added, and the mixture was stirred at 25 ° C. for 24 hours under a nitrogen atmosphere to carry out a hydrolysis reaction.
After completion of the reaction, the reaction solution was quantitatively analyzed by gas chromatography, and as a result, 474 mg of epichlorohydrin was obtained.
(5.1 mmol: yield: 51%) remained, and 310 mg (2.8 mmol) of 3-chloro-1,2-propanediol was left.
1: yield 28%). Further, as a result of analysis by high performance liquid chromatography, the selectivity of (S) -epichlorohydrin at this time was 80%, and (R) -3-chloro-
The selectivity for 1,2-propanediol was 80.5%.

Example 2 A N, N'-bis [2-
(Mesitoyl) -3-oxobutylidene]-(1S, 2
S) -1,2-Diphenylethylenediaminatocobalt (II) (36 mg, 0.05 mmol) and toluene as a solvent (3 ml) were charged, the mixture was cooled to -76 ° C., and trifluoroacetic acid (5 μl, 0.066 mmol) was added dropwise. The system was filled with air, and the mixture was stirred from -76 ° C to 25 ° C for 1.5 hours and further at 25 ° C for 1 hour using a stirrer. Then, the solvent was removed under reduced pressure and dried to obtain No. 1 in Table 1. . 2
41 mg (0.05 mmo) of cobalt (III) complex
1) was obtained. Under ice-cooling, 928 mg (10 mmol) of racemic epichlorohydrin and 182 mg (1
0 mmol) and stirred at 25 ° C. for 18 hours under a nitrogen atmosphere to carry out a hydrolysis reaction. After the completion of the reaction, the reaction solution was quantitatively analyzed by gas chromatography, and as a result, 280 mg (3 mmol: yield 30) of epichlorohydrin was obtained.
%) Remained to produce 608 mg (5.5 mmol: 55% yield) of 3-chloro-1,2-propanediol. As a result of analysis by high performance liquid chromatography, the selectivity of (S) -epichlorohydrin at this time was 8%.
The selectivity for 8% and (R) -3-chloro-1,2-propanediol was 68%.

Example 3 Under the same conditions and operations as in Example 2, 36 mg (0.05 mmol) of a cobalt (III) complex was obtained. To this, 932 mg of racemic epichlorohydrin (10 mm
ol) and 178 mg (10 mmol) of water were added, and the mixture was stirred at 5 ° C. for 92 hours in a nitrogen atmosphere to carry out a hydrolysis reaction. After completion of the reaction, the reaction solution was quantitatively analyzed by gas chromatography, and as a result, 297 mg of epichlorohydrin was obtained.
(3.2 mmol: yield 32%) remained, and 509 mg (4.6 mmol) of 3-chloro-1,2-propanediol was left.
1: 46% yield). As a result of analysis by high performance liquid chromatography, the selectivity of (S) -epichlorohydrin was 93.5% and the selectivity of (R) -3-chloro-1,2-propanediol was 68 at this time. 0.5%.

Example 4 The cobalt (II) complex used was N, N'-bis [2-
(Mesitoyl) -3-oxobutylidene]-(1R, 2
R) -1,2-Diphenylethylenediaminatocobalt (II), except that no. The cobalt (III) complex shown in 3 was obtained,
Subsequently, a hydrolysis reaction was performed under the same conditions. After completion of the reaction, the reaction solution was quantitatively analyzed by gas chromatography, and as a result, 317 mg of epichlorohydrin (3.4 mm) was obtained.
ol: yield 34%), and 501 mg of 3-chloro-1,2-propanediol (4.5 mmol: yield 45).
%). As a result of analysis by high performance liquid chromatography, the selectivity of (R) -epichlorohydrin at this time was 93%, and the selectivity of (S) -3-chloro-1,2-propanediol was 69%. there were.

Example 5 Under the same conditions and operation as in Example 2, 40 mg (0.05 mmol) of a cobalt (III) complex was obtained. To this, 1385 mg of racemic epibromohydrin (10 m
mol) and 182 mg (10 mmol) of water, and the mixture was stirred at 5 ° C. for 48 hours under a nitrogen atmosphere to carry out a hydrolysis reaction. After the reaction was completed, the reaction solution was quantitatively analyzed by gas chromatography, and as a result, epibromohydrin 485m
g (3.5 mmol: yield 35%), leaving 620 mg of 3-bromo-1,2-propanediol (4 mmol).
1: yield 40%). Further, as a result of analysis by high performance liquid chromatography, the selectivity of (S) -epibromohydrin at this time was 92%, and (R) -3-bromo-
The selectivity for 1,2-propanediol was 65%.

Example 6 A N, N'-bis [2-
(Mesitoyl) -3-oxobutylidene]-(1S, 2
S) -1,2-Diphenylethylenediaminatocobalt (II) 51 mg (0.073 mmol) and toluene 5 ml as a solvent were charged, cooled to -76 ° C., and trifluoroacetic acid 8 μl (0.1 mmol) was added dropwise. The system was filled with air, and stirred for 1.5 hours from -76 ° C to 25 ° C using a stirrer, and further stirred at 25 ° C for 1 hour.
The solvent was removed and recrystallized from hexane: dichloromethane to obtain No. 1 in Table 1. Cobalt (III) complex 5 shown in 2
1 mg (0.063 mmol) was obtained. To this, 1167 mg of racemic epichlorohydrin (12.
6 mmol) and 220 mg (12.2 mmol) of water were added, and the mixture was stirred at 25 ° C. for 24 hours under a nitrogen atmosphere to carry out a hydrolysis reaction. After completion of the reaction, the reaction solution was quantitatively analyzed by gas chromatography, and as a result, 278 mg (3 mmol: 24% yield) of epichlorohydrin remained.
707 mg of -chloro-1,2-propanediol (6.
4 mmol: yield 51%). In addition, as a result of analysis by high performance liquid chromatography, (S)-
The selectivity for epichlorohydrin was 88%, and the selectivity for (R) -3-chloro-1,2-propanediol was 65%.

EXAMPLE 7 N, N'-bis [2-
(Mesitoyl) -3-oxobutylidene]-(1S, 2
S) 35 mg (0.05 mmol) of 1,2-diphenylethylenediaminatocobalt (II) and 3 ml of toluene as a solvent were added, and the mixture was cooled to -76 ° C and 6 μl of acetic acid was added.
(0.1 mmol) was added dropwise. Fill the system with air,
After stirring from -76 ° C to 25 ° C for 1.5 hours and further at 25 ° C for 1 hour using a stirrer, the solvent was removed and dried under reduced pressure to obtain No. 1 in Table 1. Cobalt (II)
I) 40 mg (0.05 mmol) of complex were obtained. To this, 923 mg of racemic epichlorohydrin (1
0 mmol) and 183 mg (10 mmol) of water, and the mixture was stirred at 25 ° C. for 8 hours under a nitrogen atmosphere to carry out a hydrolysis reaction. After completion of the reaction, the reaction solution was quantitatively analyzed by gas chromatography, and as a result, epichlorohydrin 7
58 mg (8.2 mmol: yield 82%) remained and 3 mg
-Chloro-1,2-propanediol 155 mg (1.
4 mmol: yield 14%). In addition, as a result of analysis by high performance liquid chromatography, (S)-
Epichlorohydrin selectivity is 65.5%, (R) -3
-Chloro-1,2-propanediol selectivity is 84%
Met.

[0033]

According to the method of the present invention, under mild conditions,
An optically active form of epihalohydrin can be easily produced by a one-step reaction.

Continued on the front page (72) Inventor Hiroshi Iwane 8-3-1 Chuo, Ami-cho, Inashiki-gun, Ibaraki Pref. F-term in the Tsukuba Research Laboratory, Mitsubishi Chemical Corporation (reference) FE71 FE75 4H039 CA60 CF90

Claims (5)

[Claims] 1. An optically active epihalohydrin characterized in that a racemic epihalohydrin is hydrolyzed in the presence of an optically active transition metal complex catalyst, and the generated optically active 3-halo-1,2-propanediol is separated. Manufacturing method. 2. The method for producing an optically active epihalohydrin according to claim 1, wherein the optically active transition metal complex catalyst is an optically active cobalt (III) complex. 3. An optically active cobalt (III) complex comprising:
General formula (a)(Where R¹And R^TwoAre different from each other,
Alkyl group or aryl group which may have a substituent
It is. Also, two R¹Two or two R^TwoEach other
May combine with each other to form a ring. R^Three, R^Four
And R^FiveMay be the same or different; a hydrogen atom,
Alkyl group or aryl optionally having a substituent
Group, acyl group or alkoxycarbonyl group. Ma
R^ThreeAnd R ^Four, R^FourAnd R^FiveAre connected to each other to form a ring
It may be formed. Where R^FourAnd R^FiveIs bound to benzene
It does not form a ring. R⁶Is R⁷-CO- or
R⁸-SO_Two-Group (R⁷And R⁸Represents a substituent
Represents an alkyl group or an aryl group which may have
You. ). ) Is a complex represented by
A method for producing an optically active epihalohydrin according to claim 2
Law. 4. An optically active cobalt (III) complex represented by the general formula:
In (a), R ¹Or R^TwoOne of the pheny
A complex in which the other is a hydrogen atom.
A method for producing an optically active epihalohydrin according to claim 3
Law. 5. An optically active cobalt (III) complex represented by the general formula:
In (a), R ^ThreeIs a hydrogen atom, R^FourIs Mesitoil
Group, R^FiveIs a complex wherein is a methyl group
Production of the optically active epihalohydrin according to claim 3 or 4.
Construction method.