JPH0791217B2 - Process for producing optically active 2-phenoxybutanoic acid - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial field of application) The present invention provides an optically active compound useful as a synthetic intermediate for agricultural chemicals.
-A method for producing phenoxybutanoic acid.

Many compounds having biological activity are known as phenoxybutanoic acid derivatives. For example, JP-A-58-113155 and JP-A-58-113155
No. 2 disclosed in JP-A-58-67653 and JP-A-59-29645
-Phenoxybutanoic acid amides are useful as agricultural chemicals, especially as herbicides.

(Prior Art and Problems to be Solved by the Invention) 2-phenoxybutanoic acid has an asymmetric carbon atom at the 2-position,
The method for producing optically active 2-phenoxybutanoic acid is
Conventionally unknown. Therefore, diastereomers of optically active amines and (±) -2-phenoxybutanoic acid
An optical resolution method with salt was tried.

However, in order to obtain 2-phenoxybutanoic acid with high optical purity by this method, recrystallization is required several times or more,
Furthermore, there was a big problem in operation such that it could be divided only under very limited conditions. Furthermore, the recovery rate of the optically active substance relative to the racemate used was insufficient.

Therefore, although such a dividing method can be applied in the case of a small amount, it was very difficult to apply this method to industrially produce a large amount.

(Means for Solving the Problem) The inventors of the present invention have earnestly studied the method for producing industrially optically active 2-phenoxybutanoic acid, and have completed the present invention.

The present invention has the formula (Wherein, X represents a chlorine atom or a bromine atom, and M represents an alkali metal atom), and an alkali metal salt of R-(+)-2-halogenobutanoic acid represented by the formula: (Wherein M represents an alkali metal atom), an alkali metal salt of phenol, and a dipolar aprotic solvent,
Alternatively, the reaction is carried out at 20 to 50 ° C. in a mixed solvent of a bipolar aprotic solvent and an aprotic solvent.

formula Is a method for producing S-(−)-2-phenoxybutanoic acid.

The starting compounds of the above formulas (I) and (II) may be separately synthesized beforehand and used, or may be synthesized in a solvent and used as they are. The reaction is carried out in the following solvent.

As the solvent used in this reaction, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,3
-Use as a dipolar aprotic solvent such as dimethyl-2-imidazolidinone (DMI) and hexamethylphosphoric amide, or in the case of dipolar aprotic solvent, as a mixed solvent with aprotic solvent such as benzene, toluene and xylene. You can

As for the amount of solvent, 1 to 10 parts by weight of the solvent is used for 1 part by weight of the substrate, and 0.3 to 5 parts by weight of the dipolar aprotic solvent and 1 to the aprotic solvent are used for the mixed solvent. It is preferable to use a mixture of 10 to 10 parts by weight because the reaction proceeds well.

The reaction temperature is particularly preferably 20 to 50 ° C. The reaction time is not particularly limited, but varies depending on the solvent and the like, and is almost completed in 5 to 20 hours.

As the starting material, 0.8 to 5 equivalents of the alkali metal salt (II) of phenol may be used with respect to 1 equivalent of the alkali metal salt (I) of R-(+)-2-halogenobutanoic acid.

Examples will be shown below for further description.

Further, the optical purity of R-(+)-2-halogenobutanoic acid used here was determined by NMR using a shift reagent (Europium (HFC) 3) while leading to methyl ester while maintaining the optical activity. Further, the optical purity of the obtained 2-phenoxybutanoic acid was calculated based on the degree of optical rotation of a standard product having an optical purity of 100% which was previously obtained by optical resolution.

Example 1 Preparation of S-(-)-2- (4-fluoro-3-trifluoromethyl) phenoxybutanoic acid in DMF 16.05 g of potassium salt of R-(+)-2-chlorobutanoic acid
(0.1 mol) and potassium salt of 4-fluoro-3-trifluoromethylphenol (32.7 g, 0.15 mol) in 60 ml of DM
It was added to F and stirred at 27 to 30 ° C. for 10 hours. After stirring, 2
The oily substance was adjusted to pH 1 with an aqueous N hydrochloric acid solution and the oily substance was extracted with ether, and the ether layer was washed with a saturated aqueous sodium hydrogen carbonate solution. The saturated aqueous sodium hydrogen carbonate solution was adjusted to pH 1 with 2N-hydrochloric acid, and the liberated oily substance was extracted with ether. The ether was dried over anhydrous magnesium sulfate, evaporated under reduced pressure, and the residue was distilled under reduced pressure to obtain the desired product.

bp155-160 ℃ / 4mmHg 80% yield The optical purity of the optically active 2-chlorobutanoic acid used is ee =
92%, the optical purity of the obtained phenoxybutanoic acid is ee = 90
%Met.

Example 2 S-(-)-2- (4 in DMI-benzene system
Synthesis of -fluoro-3-trifluoromethyl) phenoxybutanoic acid 16.05 g of potassium salt of R-(+)-2-chlorobutanoic acid
(0.1 mol) and 4-fluoro-3-trifluoromethylphenol potassium salt 21.8 g (0.1 mol), benzene 7
The mixture was added to a mixed solvent of 0 ml and DMI (12 ml) and stirred at 30 ° C for 8 hours. After completion of stirring, the pH was adjusted to 1 with a 2N aqueous hydrochloric acid solution, 200 ml of benzene was further added, the benzene layer was separated, washed with water, benzene was distilled off under reduced pressure, and the residue was distilled under reduced pressure to obtain 22 g of the target product. Yield 80%.

Optical purity of optically active 2-chlorobutanoic acid used ee = 98
%, The optical purity of the obtained phenoxybutanoic acid is ee = 96%
Met.

Table 1 collectively shows the above-described examples and examples under various conditions.

(Effects of the Invention) As is clear from the above examples, according to the method of the present invention, the desired optically active phenoxybutanoic acid can be obtained with a high yield and a high optical purity.

 ─────────────────────────────────────────────────── ─── Continuation of the front page (56) References JP-A-55-62043 (JP, A) JP-A 52-17431 (JP, A) JP-A 50-140632 (JP, A)

Claims (1)

[Claims] 1. A formula (Wherein, X represents a chlorine atom or a bromine atom, and M represents an alcar metal atom), and an alkali metal salt of R-(+)-2-halogenobutanoic acid represented by the formula: (Wherein M represents an alkali metal atom), and an alkali metal salt of phenol, in a dipolar aprotic solvent or a mixed solvent of a dipolar aprotic solvent and an aprotic solvent, 20 It is characterized by reacting at -50 ° C. formula The manufacturing method of S-(-)-2-phenoxybutanoic acid shown by these.