JPH01316331A - Production of optically active 1-(pentafluorophenyl) ethanol - Google Patents

Abstract

PURPOSE:To obtain optically active 1-(pentafluorophenyl)ethanol from relatively inexpensive raw materials by simple operation by reacting an optically active 2-halo-1-(pentafluorophenyl)ethanol with an organotin hydride. CONSTITUTION:An optically active 2-halo-2-(pentafluorophenyl)ethanol shown by the formula (X is halogen; C* is inert carbon) is reacted with an organotin hydride shown by the formula R4-mSnHm (R is 1-7C hydrocarbon group; m is 1 or 2) to advantageously obtain optically active 1-(pentafluorophenyl)ethanol extremely useful as an optical resolving agent for microanalysis, electron scavenger and further as an intermediate for drugs, agricultural chemicals and functional organic materials. The compound shown by the formula is obtained by reacting optically active 2,3,4,5,6-pentafluorostyrene oxide with a compound shown by the formula Li2MX4 (M is Cu or Ni; X is halogen).

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention relates to a method for producing optically active 1-(pentafluorophenyl)ethanol.

[Prior Art] Many fluorine-containing compounds generally have unique physical properties and physiological activities, and among these, compounds having a pentafluorophenyl group are used as electron capture agents in trace analysis [e.g. , Analytical Chemistry (
Anal, Chem,).

±standing, 2073 (I963)). Among the compounds having this pentafluorophenyl group, one having optical activity
-(Pentafluorophenyl)ethanol is obtained by optical resolution and by asymmetric reduction of methyl (pentafluorophenyl) ketone in the presence of optically active binaphthol [Liebigs-Annalen-Der.・Hemi (Liebigs Ann, Ch.
eap, ), 1986.

2004).

[Problems to be Solved by the Invention] The above-mentioned optical resolution method requires a special optical resolution agent, requires complicated steps, and is complicated to operate.

On the other hand, the method using asymmetric reduction requires the use of an expensive asymmetric source such as optically active binaphthol, resulting in a problem of high production costs.

The present invention has solved this problem, and has achieved optical activity using relatively inexpensive raw materials and simple reaction operations.
An object of the present invention is to provide a method for producing -(pentafluorophenyl)ethanol.

[Means for Solving the Problems] The present invention provides optically active 2-halo 1-(pentafluoro phenyl) ethanols according to the following formula (II) R, -nsnHl (n) (in the formula,
R represents a hydrocarbon group having 1 to 7 carbon atoms, which may be the same or different from each other, and n is 1 or 2).

Optically active 2-halo 1-(pentafluorophenyl)ethanols, which are the starting materials of the present invention, contain optically active 2,3,4,5,6-pentafluorostyrene oxide of the formula Li, MX4 (in the formula M represents Cu or Ni, and X represents halogen).

In this reaction, a compound represented by the following formula (III) (wherein X represents a halogen and C! represents an asymmetric carbon atom) is produced as a by-product, but this compound does not particularly need to be separated. This is because it is relatively difficult to separate the compound of formula (I) and the compound of formula (III) above, which are the starting materials of the present invention; rather, they are reacted as a mixture with an organic tin hydride, and then the product is produced. Separation is easier if it is separated by .

The above-mentioned 2,3,4,5.6-pentafluorostyrene oxide having optical activity can inhibit microorganisms having epoxide-producing ability belonging to the genus Nocardia with 2.3,4,5.6-pentafluorostyrene oxide.
- Can be obtained relatively easily and inexpensively by a method of acting on pentafluorostyrene (Patent application No. 62
-233497).

X in the above formula (I) may be any halogen atom, but from the viewpoint of ease of reaction and availability, chlorine or bromine is preferred, and bromine is particularly preferred.

On the other hand, the organic tin hydride represented by formula (II) includes trimethyltin hydride, triethyltin hydride,
Tributyltin hydride, triphenyltin hydride,
Examples include dibutyltin hydride and diphenyltin hydride.

The reaction between the formula (I) and the formula (■) may be carried out without a solvent, but it is preferable from the viewpoint of reaction efficiency to carry out the reaction in the presence of a reaction solvent. In this case, the reaction solvent may be a hydrocarbon solvent such as hexane or benzene, or an ether solvent such as diethyl ether. In addition, as a reaction initiator, for example, α,α'-azobisisobutyronitrile (AIBN
) etc. can be added to the reaction system to promote the reaction efficiently.

[Example] Reference Example 1 10.5 g of (R)-(+)-2,3,4,5,6-pentafluorostyrene oxide was added to 1 part of tetrahydrofuran.
Lithium bromide was dissolved in
3 g and 16.8 g of cupric bromide in 15 g of tetrahydrofuran.
A solution of Li2CuBr4 prepared by dissolving in 0ml was added dropwise. After completion of the dropwise addition, the mixture was stirred at room temperature for 2 hours, and the resulting reaction mixture was poured into 0.05M phosphate buffer and extracted with ether. The obtained extract was dried over anhydrous magnesilla sulfate 11, the solvent was distilled off under reduced pressure, and 2-bromo-2
(R)-2-bromo-1-(pentafluorophenyl) containing 20% -(pentafluorophenyl)ethanol
11.9 g of ethanol was obtained.

(R)-2-bromo-1 obtained by the method of Reference Example 1 above
- Dissolve 11°3 g of (pentafluorophenyl)ethanol in 50 ml hexane and add 1 ml of tributyltin hydride.
1.4 ml was added at room temperature. After stirring and reacting at 60° C. for 8 hours, the solvent was distilled off under reduced pressure, purified by silica gel column chromatography, and distilled under reduced pressure to obtain 4.0 g of a compound having the following physical properties. From this physical property, it was confirmed that the compound was (S)-(-)-1-(pentafluorophenyl)ethanol.

JI NMR (CDCI, ): 1.63 (3H, d
, 6.8Hz), 2.43(LH.

bs), 5.24 (IH, q, 6.811z) [α] effect: -8, 1 (c2.7. pentane) five main points (R) - (+) -2, 3, 4, 5 , 10.5 g of 6-pentafluorostyrene oxide in 1 part of tetrahydrofuran
Lithium chloride 6
．． 4g and cupric chloride 10.1g in tetrahydrofuran 1
A solution of Li and CuBr4 prepared by dissolving them in 50ml was added dropwise. After completion of the dropwise addition, the mixture was stirred at room temperature for 20 hours, and the resulting reaction mixture was poured into a 0.05M phosphate buffer and extracted with ether.

The obtained extract was dried over anhydrous magnesium sulfate, the solvent was distilled off under reduced pressure, and (R)-2-chloro-1-(pentafluorophenyl) containing 20% of 2-chloro-2-(pentafluorophenyl)ethanol was extracted. fluorophenyl) ethanol 12.0
I got g.

Abortion history and (R)-2-chloro-1 obtained by the method of Reference Example 2 above
-(pentafluorophenyl)ethanol 1.23g,
Tributyltin hydride 1, 60 ml, AIBN
16 mg were mixed and stirred and reacted at 80° C. for 8 hours. After the reaction was completed, the reaction mixture was purified by silica gel column chromatography to obtain 0.7 g of (S)-(-)-1-(pentafluorophenyl)ethanol.

1111 0.76 g of lithium aluminum hydride was suspended in 15ff11 of dry ether, and 20+ of dry ether was added to it.
6.8 gg of diphenyltin dichloride dissolved in al was added under water cooling, and the mixture was stirred for 30 minutes.

20 ml of water was added to the resulting reaction mixture, and the ether phase was washed with ice water, dried over calcium chloride, and concentrated under reduced pressure to prepare diphenyltin hydride.

2.47 g of (R)-2-chloro-1-(pentafluorophenyl)ethanol obtained by the method of Reference Example 2 was added to this diphenyltin hydride, and the mixture was stirred at 60° C. for 1 hour to react. AIBN 2 was added to the resulting reaction mixture.
After adding 0 mg and stirring at 60°C for an additional 3 hours,
Distillation under reduced pressure yielded 0.3 og of (S)-(-)-1-(pentafluorophenyl)ethanol.

[Effects of the Invention] The present invention uses relatively inexpensive raw materials to react optically active 2-halo 1-(pentafluorophenyl)ethanol with an organic tin hydride, thereby producing optically active 1-(pentafluorophenyl) ethanol through a simple reaction operation. It has the special effect of producing ethanol (fluorophenyl).

In addition, the optically active 1-(pentafluorophenyl)ethanol obtained in the present invention is extremely useful as an optical resolution agent and electron capture agent for trace analysis, and as an intermediate in the production of pharmaceuticals, agricultural chemicals, functional organic materials, etc. It is something.

Claims (1)

[Claims] Optical activity 2 represented by the following formula (I) ▲Mathematical formulas, chemical formulas, tables, etc.▼(I) (In the formula, X represents a halogen and C^* represents an asymmetric carbon) -Halo-1-(pentafluorophenyl)ethanol is represented by the following formula (II) R_4_-_nSnHn(II) (wherein, R represents a hydrocarbon group having 1 to 7 carbon atoms that is the same or different from each other, and n is 1 or 2)).