JPH06172237A - Production of 1-halogeno-3,3,3-trifluoro-2-propanol - Google Patents

Abstract

PURPOSE:To readily obtain the subject compound having a high optical purity at a low cost by selectively halogenating readily available 3,3,3- trifluoropropan-1,2-diol, especially an optically active substance with a halogenating agent. CONSTITUTION:The primary hydroxyl group in 3,3,3-trifluoropropan-1,2-diol is selectively halogenated with a halogenating agent (phosphorus pentachloride or sulfuryl chloride is especially preferred) to afford the objective 1- halogeno-3,3,3-trifluoro-2-propanol. An optically active substance having methine carbon in which trifluoromethyl group and secondary hydroxyl group are bound as the asymmetric center is especially preferred as the 3,3,3-trifluoropropan-1,2- diol. The produced compound is useful as a raw material for physiologically active substances such as a medicine or an agrichemical, functional organic compounds such as a liquid crystal, a surfactant or a dye, functional material polymers, etc., and further 1,2-epoxy-3,3,3-trifluoropropane.

Description

Detailed Description of the Invention

[0001]

The present invention relates to a physiologically active substance such as pharmaceuticals and agricultural chemicals, a liquid crystal, a surfactant, a functional organic compound such as a dye,
Functional materials such as polymer, 1,2-epoxy-3,
The present invention relates to a method for producing 1-halogeno-3,3,3,3-trifluoro-2-propanol, which is useful as a raw material for 3,3-trifluoropropane, and particularly an optically active substance thereof.

[0002]

2. Description of the Related Art In general, a compound obtained by replacing hydrogen in a known compound having functionality or physiological activity with fluorine has its function or physiological activity enhanced by a specific electronic effect of the fluorine atom, or has a new function or physiological activity. It is known to obtain activity. Therefore, a fluorine-containing building block having a structure similar to the starting material of a known compound has been designed and synthesized [for example, "Fluorine-based physiologically active substances in the 90's," supervised by Nobuo Ishikawa, CMC (1991)].

1-halogeno-2-propanol is one of the basic synthetic raw materials and is widely used as a raw material for various chemical products. The fluorine-substituted compound, 1-halogeno-3,3,3-trifluoro-2-propanol, and particularly its optically active substance have been considered to be useful starting compounds. As a method for producing this compound, a method for producing optically inactive 1-bromo-3,3,3-trifluoro-2-propanol by reducing 3-bromo-1,1,1-trifluoropropanone [ ETMcBee, TMBurton, J.Am.Chem.S
oc., 74 , 3022 (1952)], 3,3,3-trifluoropropene oxide is reacted with hydrogen chloride in an anhydrous ether solvent [Japanese Patent Application No. 3-214179]. However, 1-bromo-3,3, obtained by the former method,
3-Trifluoro-2-propanol is optically inactive, and the latter method has an optical purity of 3,3,3-
Determined by trifluoropropene oxide.
Therefore, at present, it is impossible to synthesize optically active 1-halogeno-3,3,3-trifluoro-2-propanol having an optical purity of 75% ee or more. Ie 100%
No method for obtaining 1-halogeno-3,3,3-trifluoro-2-propanol of ee has been known so far.

[0004]

SUMMARY OF THE INVENTION The present invention has been made in view of the above situation, and the object of the present invention is to:
An object of the present invention is to provide a method for inexpensively and conveniently producing 1-halogeno-3,3,3-trifluoro-2-propanol, particularly an optically active substance having 100% ee thereof.

[0005]

The present inventors have found that the optical purity is 7
An optical purity of 75% ee3 obtained by hydrolyzing 5% ee of optically active 3,3,3-trifluoropropene oxide,
A method for producing 3,3,3-trifluoropropane-1,2-diol having an optical purity of 100% ee was developed by recrystallizing 3,3-trifluoropropane-1,2-diol (Japanese Patent Application (See Japanese Patent Publication No. 3-27642). The primary hydroxyl group of this compound is selectively halogenated to obtain an optical purity of 100.
It was found that 1-halogeno-3,3,3-trifluoro-2-propanol with% ee can be synthesized.

The present invention has been made on the basis of such findings, and it is because the primary hydroxyl group of 3,3,3-trifluoropropane-1,2-diol is selectively halogenated by using a halogenating agent. In the method for producing 1-halogeno-3,3,3-trifluoro-2-propanol,
An optically active 1-halogeno-3 using an optically active substance in which a methine carbon having a trifluoromethyl group and a secondary hydroxyl group bonded as an asymmetric center is used as 3-trifluoropropane-1,2-diol. The method for producing 3,3,3-trifluoro-2-propanol further comprises:
Preferably phosphorus pentachloride, phosphorus pentabromide, sulfuryl chloride,
It consists of using carbon tetrachloride = trialkylphosphine or carbon tetrabromide = trialkylphosphine.

The starting material of the present invention, 3,3,3-trifluoropropane-1,2-diol, is 1,2-epoxy-
It can be conveniently obtained by hydrolyzing 3,3,3-trifluoropropane. On the other hand, this optically active substance, especially 3,3,3-trifluoropropane- having an optical purity of 100% ee.
1,2-diol is 1,2-diol having an optical purity of 75 to 77% ee, which is obtained by microbial oxidation of trifluoropropene.
2-epoxy-3,3,3-trifluoropropane
(See Japanese Patent Publication No. 1-14798), it can be obtained by a method of recrystallizing 3,3,3-trifluoropropane-1,2-diol having an optical purity of 75 to 77% ee obtained by hydrolysis ( (See Japanese Patent Application No. 3-27642).

This 3,3,3-trifluoropropane-1,
By reacting a 2-diol with a halogenating agent,
The primary hydroxyl group is halogenated and is the object of the present invention. 1
-Halogeno-3,3,3-trifluoro-2-propanol can be obtained. In this case, an optically active substance having an optical purity of 100% ee is used as the 3,3,3-trifluoropropane-1,2-diol. When used, 1-halogeno-3,3,3-trifluoro- with an optical purity of 100% ee with almost no racemization
2-Propanol is obtained.

In the present invention, only the primary hydroxyl group of the two hydroxyl groups is selectively halogenated. Therefore, a halogenating agent which has good regioselectivity and which does not interfere with the reaction by the remaining secondary hydroxyl group is used. Desired. In addition, the optical purity of the product is required to be the same as that of the starting material, and thus it is required to be a halogenating agent that does not cause racemization of the starting material and the product in the course of the halogenation reaction. As a halogenating agent satisfying such conditions, phosphorus pentachloride, phosphorus pentabromide, sulfuryl chloride, methanesulfonyl chloride, p-toluenesulfonyl chloride, titanium tetrachloride, phosphorus trichloride, phosphorus tribromide, thionyl chloride, Examples thereof include silicon tetrachloride, tin dichloride, hydrogen chloride, carbon tetrachloride = triphenylphosphine, carbon tetrabromide = trialkylphosphine, and among these, particularly preferred are phosphorus pentachloride and sulfuryl chloride. is there.

This reaction is preferably carried out in the presence of a reaction solvent, and this solvent is not particularly limited as long as it does not react with the halogenating agent used. Specific examples thereof include hydrocarbons such as hexane and benzene, ethers such as ethyl ether, dibutyl ether and diglyme, and halogen compounds such as methylene chloride and chloroform. In particular, the produced 1-halogeno-3,
High-boiling ethers, especially diglyme, which can easily separate 3,3-trifluoro-2-propanol,
Dibutyl ether and the like are preferable. However, hydrocarbons having low polarity are not preferable because the chlorination reaction may become extremely difficult to proceed.

The reaction conditions are appropriately selected depending on the halogenating agent used.

The reaction is terminated by gas chromatography, NM
It can be confirmed by ordinary analytical means such as R.

1-halogeno-3 thus obtained,
3,3-trifluoro-2-propanol can be purified by distillation or the like.

The optical purity of these 1-halogeno-3,3,3-trifluoro-2-propanols can be determined by, for example, propionyl esterification of the secondary hydroxyl group using propionyl chloride in the case of chloride, followed by optical resolution. It can be determined using a gas chromatograph method (CP Cyclodex β236M column, manufactured by GL Science).

A specific manufacturing method will be described below with reference to examples.

[0016]

【Example】

Example 1 0.65 g (5 mmol) of 3,3,3-trifluoropropane-1,2-diol having an optical purity of 75% ee was added to about 10 m.
Dissolved in l diglyme. While cooling the container so as to keep it at room temperature, 3.35 g (25 mmol) of sulfuryl chloride was added dropwise.

After completion of the dropping, the reaction solution was heated to 80 using an oil bath.
Heated to ~ 100 ° C. Gases such as hydrogen chloride and sulfur oxide were generated with heating. The completion of the reaction was confirmed by the stoppage of the generation of gas. Then, water is added to the reaction mixture to decompose unreacted chlorinating agent and the like, and then the mixture is extracted with ether, and the ether phase is washed with an aqueous solution of sodium hydrogen carbonate and a saline solution, and anhydrous sodium sulfate is used. It was dried and dried, and then subjected to gas chromatographic analysis. As a result, another method [a method for synthesizing 3,3,3-trifluoropropene oxide by reacting with hydrogen chloride in an anhydrous ether solvent (Japanese Patent Application No. 3-214179) )] And the same as 1-chloro-3,3,3-trifluoro-2-propanol. In addition, this compound had the following physical properties.

Bp: 60 ° C./100 mmHg, ¹ H-NMR (CDCl ₃ ) δ: 3.75 (m, 3H), 4.15 (m, 1H) ppm. IR (neat): 3320 cm ^-1 .MS (rel.Int.): 49 (20), 51 (23), 69 (10), 79 (1
00), 81 (41), 99 (20)

From this result, the product is 1-chloro-3,3,
It was confirmed to be 3-trifluoro-2-propanol, and the yield determined by gas chromatography was about 40%.

1-chloro-3,3, thus obtained,
An excess amount of propionyl chloride and pyridine was added to an ether solution of 3-trifluoro-2-propanol to propionylate a secondary hydroxyl group, and 2-ethylcarbonyloxy-1-chloro-3,3,3-tri After making fluoropropane, its optical purity was measured by an optical resolution gas chromatographic method. The optical purity of the obtained compound was 75% as that of 3,3,3-trifluoropropane-1,2-diol as a raw material. It was confirmed to be% ee.

(Example 2) 3,3,3 having an optical purity of 75% ee
-Trifluoropropane-1,2-diol 0.65 g (5 mmo
l) dissolved in about 5 ml of diglyme, while cooling the reaction vessel to keep it at room temperature, 1.04 g (5 m) of phosphorus pentachloride.
(mol) in a diglyme solution. After the dropping was completed, the reaction solution was heated to 80 to 100 ° C using an oil bath. Gases such as hydrogen chloride were generated with heating. Then, heating was continued for 2 hours to complete the reaction. Then, water is added to the reaction mixture to decompose unreacted chlorinating agent and the like, and then the mixture is extracted with ether, and the ether phase is washed with an aqueous sodium hydrogen carbonate solution and brine, and anhydrous sodium sulfate is used. It was confirmed that it was the same as 1-chloro-3,3,3-trifluoro-2-propanol produced by an alternative method when subjected to gas chromatographic analysis after being dried. The yield of this product obtained by gas chromatography was approximately 10%.

1-chloro-3,3, thus obtained,
An excess amount of propionyl chloride and pyridine was added to an ether solution of 3-trifluoro-2-propanol to propionylate a secondary hydroxyl group, and 2-ethylcarbonyloxy-1-chloro-3,3,3-tri After making fluoropropane, its optical purity was measured by an optical resolution gas chromatographic method. The optical purity of the obtained compound was 75% as that of 3,3,3-trifluoropropane-1,2-diol as a raw material. It was confirmed to be% ee.

(Example 3) By the method described in Example 1, 7
Instead of 0.65 g (5 mmol) of 3,3,3-trifluoropropane-1,2-diol having 5% ee, 0.65 g of 3,3,3-trifluoropropane-1,2-diol having 100% ee (5 mmol)
Experiment was carried out using. The product was converted to propionyl ester by the method described in Example 1 and the optical purity was determined. As a result, it was confirmed that the product had an optical purity of 99.5% ee or more.

(Example 4) By the method described in Example 2, 7
Instead of 0.65 g (5 mmol) of 3,3,3-trifluoropropane-1,2-diol having 5% ee, 100% ee 3,3,3-trifluoropropane-1,2-diol 0.65 g (5 mmol) ) Was used to conduct the experiment. The product was converted to propionyl ester by the method described in Example 1 and the optical purity was determined. As a result, it was confirmed that the product had an optical purity of 99.5% ee or more.

[0025]

INDUSTRIAL APPLICABILITY The present invention provides 1-halogeno-3,3,3-trifluoro-2-propanol which is an industrially useful fluorine-containing raw material compound, in particular, an optically active substance having a high optical purity, simply and easily. It can be manufactured at low cost. Therefore, according to the present invention, it becomes possible to inexpensively obtain optically active 1-halogeno-3,3,3-trifluoro-2-propanol having a high optical purity, which has not been heretofore known, and to obtain this compound. It becomes possible to develop a functional organic substance as a raw material, and to manufacture those compounds easily and inexpensively.

Claims (3)

[Claims] 1. 3,3,3-Trifluoropropane-1,2-
1-halogeno-3,3,3 characterized by selectively halogenating the primary hydroxyl group of a diol with a halogenating agent
-Method for producing trifluoro-2-propanol. 2. The methine carbon having a trifluoromethyl group and a secondary hydroxyl group as the 3,3,3-trifluoropropane-1,2-diol as the asymmetric center according to claim 1. Optically active 1-halogeno-3,3,3-trifluoro-2 characterized by using an optically active substance
-Method for producing propanol. 3. The method according to claim 1, wherein phosphorus pentachloride, phosphorus pentabromide, sulfuryl chloride, carbon tetrachloride = trialkylphosphine, or carbon tetrabromide = trialkylphosphine is used as the halogenating agent. And a method for producing 1-halogeno-3,3,3-trifluoro-2-propanol.