JPH0460590B2 - - Google Patents

Description

[Detailed description of the invention]

(Industrial Application Field) The present invention relates to optically active chlorohydrin derivatives. More specifically, the present invention relates to highly purified optically active chlorohydrin derivatives useful as synthetic intermediates for pharmaceuticals, agricultural chemicals, other physiologically active substances, ferroelectric liquid crystal materials, and the like. (Prior Art and Problems) In recent years, the usefulness of optically active organic compounds has been increasing not only in the field of medicines, agricultural chemicals, and other physiologically active substances, but also in the field of new materials such as ferroelectric liquid crystal materials. It is extremely important to obtain these optically active compounds with high optical purity, and the problem is how to obtain optically active substances with high purity. (Means for Solving the Problem) The present applicant has previously proposed a method for producing optically active epichlorohydrin with high optical purity (Japanese Patent Application Laid-open Nos. 132196/1982 and 6697/1987). The present inventors attempted to synthesize a new compound using the above optically active epichlorohydrin as a raw material, and as a result, succeeded in obtaining an optically active chlorohydrin derivative with high optical purity that can be used as a raw material for the above new material. The present invention is based on the following formula () (However, in the above formula (), R ¹ is hydrogen,
Each represents a group selected from straight-chain alkyl, branched alkyl, alkenyl, and aralkyl having 1 to 22 carbon atoms, and * represents an asymmetric carbon atom. The optically active chlorohydrin derivative of the present invention can be produced by the following method. It can be obtained by reacting optically active epichlorohydrin () with a hydrogen nucleophile or a carbon nucleophile, preferably in the presence of a monovalent copper compound. Examples of the hydrogen nucleophile used in the above reaction include sodium borohydride, lithium aluminum hydride, sodium hydride, and lithium hydride. In addition, as a carbon nucleophile, R ¹ M or
Examples include organometallic compounds represented by R ¹ MgX. Here R ¹ represents the same group as R ¹ in formula (),
M represents an alkali metal such as lithium or sodium or an alkaline earth metal such as calcium or magnesium. X represents a halogen atom such as a chlorine atom, a bromine atom, or an iodine atom. Specific examples of R ¹ above include methyl, ethyl,
n-propyl, n-butyl, n-pentyl, n-
hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tridecyl, n-tetradecyl, n-pentadecyl, n-hexadecyl, n-heptadecyl, n-octadecyl, Straight chain alkyl groups having 1 to 22 carbon atoms such as n-nonadecyl, n-icosyl, n-henicosyl, n-docosyl, isopropyl,
Isobutyl, neobutyl, 1-methylbutyl, 2
-Methylbutyl, 3-methylbutyl, 1,2-dimethylpropyl, 1-ethylpropyl, 1,1-
dimethylpropyl, 2,2-dimethylpropyl,
1-methylpentyl, 2-methylpentyl, 3-
Methylpentyl, 4-methylpentyl, 1-ethylbutyl, 2-ethylbutyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 1,2-dimethylbutyl, 1,3-
dimethylbutyl, 2,3-dimethylbutyl, 1-
Branched alkyl groups having 1 to 22 carbon atoms such as ethyl-2-methylpropyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, vinyl, allyl, 1-propenyl, 1-methylethynyl ,2-methyl-1-propenyl,1-methyl-
1-propenyl, 1-butynyl, 2-butynyl,
3-butynyl, 1-methyl-2-propenyl, 2
-Alkenyl groups having 1 to 22 carbon atoms such as methyl-2-propenyl, prenyl, geranyl, and pharnesyl, and benzyl groups substituted with 1 to 5 methyl or methoxyl groups at the ortho, meta, and para positions. Examples include aralkyl groups having 1 to 22 carbon atoms. When reacting optically active epichlorohydrin with a carbon nucleophile, a monovalent copper compound such as copper iodide,
It is preferable to use copper cyanide as a catalyst because the yield is significantly improved. The appropriate amount of catalyst to be used is 0.05 to 0.2 equivalents based on the raw material epichlorohydrin. In the reaction, the proportion of hydrogen nucleophile or carbon nucleophile may be 1 to 1.5 equivalents to epichlorohydrin, and the reaction is preferably carried out at a temperature of -78 to -30°C. The reaction system is carried out in the presence of an organic solvent. The organic solvent is preferably an ether solvent such as tetrahydrofuran, diethyl ether, ethylene glycol dimethyl ether, dimethylene glycol dimethyl ether, or a mixed solvent thereof. The optically active chlorohydrin derivative obtained according to the present invention can be converted into an optically active secondary alcohol of high purity, for example, 94% ee, by subsequent reaction with another type of nucleophile. For example, the following formula ()-1, which is one of the derivatives of the present invention The optically active chlorohydrin represented by can be converted into optically active sulcatol (94% ee), which is conventionally known as a natural insect pheromone, by reacting with thiophenol and then reducing it.

[Formula] The present invention will be explained below with reference to Examples. Example 1 (R)-(+)-1-chloro-6-methyl-5-
Synthesis of hepten-2-ol K0273 A suspension of 572 mg (3 mmol) of cuprous iodide in 10 ml of tetrahydrofuran was placed in a reaction vessel, and prenyl chloride was added to it at -30°C under an argon atmosphere.
3.14g (30m mol) and magnesium 0.92g (40m
mol) in 25 ml of tetrahydrofuran was added and stirred for 30 minutes. Then, at the same temperature, JP-A-61-132196 and JP-A-62
1.85 g (20 m
Add 5 ml of tetrahydrofuran solution of 3 mol)
After stirring for an hour, the mixture was gradually warmed to room temperature and stirred for an additional 10 hours. After the reaction was completed, 15 ml of saturated ammonium chloride water was added, diluted with 50 ml of ether, and filtered through Celite.
Separate and remove the organic layer, and dissolve the aqueous layer in ether 50ml x 2.
Extracted twice. Combine the organic layers and add 40ml of saturated saline.
After washing with water, it was dried with magnesium sulfate. The crude product obtained after distilling off the solvent under reduced pressure at 40°C or less was subjected to column chromatography using 70 g of silica gel, and the target product as a colorless liquid was obtained from a hexane:ether = 6:1 (volume) stream. g (yield 44.2%) was obtained. The properties of the obtained chlorohydrin were as follows. [α] ²⁵ _D = +1.78° (C = 3.37, CHC ₃ ) bp = 100 to 110°C (18 mmHg, Kugelrohr) IR νmax cm ^-1 (neat) 3400 NMR (CDC ₃ ) δ: 1.4 to 1.7 (2H , m) 1.62 (3H, br s) 1.69 (3H, br s) 1.9~2.3
(3H, m, 1H disappeared with D ₂ O) 3.3~3.6 (2H, m) 3.65~3.95 (1H, m) 5.11 (1H, br t, J=7Hz) MS (m/e), 162 (M ⁺ ), 69, 40 (100%) Elemental analysis C ₈ H ₁₅ OC C H C Theoretical value (%) 59.07 9.30 21.80 Measured value (%) 58.93 9.56 21.57 Example 2 (R)-(+)-1-chlorononane- Synthesis of 2-ol K0274 1.9 g (10 mmol) of cuprous iodide in 75 ml of ether
The suspension was placed in a reaction vessel and heated under a nitrogen stream for −30°C.
Add Grignard reagent prepared from 12.38 g (75 mmol) of hexyl bromide and 2 g (82.5 mmol) of magnesium in 75 ml of tetrahydrofuran at 30°C.
After stirring for a minute, the same temperature as in Example 1 (R)-
A mixed solution of 4.63 g (50 mmol, 99% ee) of epichlorohydrin in tetrahydrofuran-ether (1:
1) Added 100ml and stirred for 2 hours. After the reaction was completed, 100 ml of saturated ammonium chloride water was added, the temperature was returned to room temperature, the mixture was extracted with ether, washed with saturated brine, and the organic layer was dried over magnesium sulfate. The solvent was then distilled off under reduced pressure, and the residue was purified by distillation under reduced pressure to obtain 6.29 g (35.2 mmol, yield 70%) of the desired product. The properties of the obtained chlorohydrin were as follows. [α] ²⁵ _D = +8.20° (neat) bp = 60~66℃ (14mmHg, Kugelrohr) IR νmax cm ^-1 (neat) 3380 NMR (CDC ₃ ) δ: 0.7~1.8 (15H, m) 2.2 ( 1H, br d) 3.3 to 3.9 (3H, m) (Effects of the invention) The optically active chlorohydrin derivative of the present invention has high purity, and therefore can be used as a pharmaceutical as a highly purified optically active substance.
It is useful as a synthetic raw material for agricultural chemicals, physiologically active substances, and ferroelectric liquid crystal materials.

Claims (1)

[Claims] 1. An optically active chlorohydrin derivative represented by the following formula (). (However, in the above formula (), R ¹ is hydrogen,
Each represents a group selected from straight chain alkyl, branched alkyl, alkenyl and aralkyl having 1 to 22 carbon atoms, * represents an asymmetric carbon atom)