JPH0611736B2 - Process for producing optically active α- (4-hydroxyphenoxy) propionic acid ester - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION (Field of Industrial Application) The present invention relates to an optically active α- (4-hydroxyphenoxy).
The present invention relates to a novel method for producing a propionic acid ester.

The compound obtained by the method of the present invention is useful as a synthetic intermediate for various optically active phenoxypropionic acid herbicides. That is, the optically active α obtained by the method of the present invention
Examples of the-(4-hydroxyphenoxy) propionic acid ester include fluazifop-butyl, quino-fopethyl,
It can be usefully used as an intermediate such as diclofop-methyl, trifop-methyl and phenoxaprop-ethyl.

(Prior Art and Problems) Many known examples of a method for producing a ramice body of an α- (4-hydroxyphenoxy) propionic acid ester are known. For example, JP-A-54-19,925, 56-5
9,718,58-183,666,59-95,23
7, 60-94, 935, 60-209, 548.

However, in any case, since these are ramices, in order to obtain D-form having high herbicidal activity, the optically active form must be further separated and purified by optical resolution or the like. Therefore, such a method cannot always be said to be an efficient manufacturing method in consideration of purification loss due to optical resolution and the like. Furthermore, any of the above methods is a method of obtaining a target product by corresponding hydroquinone and a corresponding propionic acid derivative, and also as a method for producing a ramice body with a by-product of an unnecessary bis-substituted product other than the target hydroquinone-substituted product A more efficient manufacturing method is desired. There are some known attempts to selectively obtain mono-substituted compounds (Japanese Patent No. 59-231,044, US Pat. No. 4,368,06).
8, published gazettes, 57-501, 178), all of which are lamice bodies, and the complexity of the above-mentioned optical division operation has not been solved. As a method for directly obtaining an optically active α- (4-hydroxyphenoxy) propionic acid ester, a method of obtaining a target by a stereo-inversion reaction of p-hydroxybenzaldehyde and an optically active α-substituted propionic acid ester is known. (Kaikaisho 60-81, 150). However, one raw material, p-hydroxybenzaldehyde, is
For example, it can be obtained by the Liemer Tiemann reaction,
There is a problem that the yield is extremely low, and a large amount of salicylaldehyde is by-produced [Organic Reaction Vol. 28,
16 (1982)]. The Gatterman reaction can also be used, but in this case, although the para selectivity is high, an extremely low yield (organic reaction 9
Vol. 41 (1957)), and there is a safety problem such as using hydrogen cyanide as a reaction reagent. In either case, p-hydroxybenzaldehyde does not have an efficient production method, is an expensive reagent as a starting material, and is economically disadvantageous.

(Means for Solving Problems) An object of the present invention is to provide a promising optically active α as a herbicide intermediate.
An object of the present invention is to provide a method for efficiently obtaining-(4-hydroxyphenoxy) propionic acid ester by solving the above-mentioned various problems and using an inexpensive raw material.

The present invention relates to 4-hydroxyacetophenone having the general formula (In the formula, X is a halogen atom or a sulfonyloxy group, and R is a lower alkyl group. * Indicates an asymmetric carbon), and the resulting product is treated with a peracid. , An optically active α-characterized by solvolysis
This is a method for producing (4-hydroxyphenoxy) propionic acid ester.

The method of the present invention mainly comprises three reaction steps. That is, the first step is a stereospecific substitution reaction between 4-hydroxyphenoxyacetophenone and the compound of the general formula (1). 4-Hydroxyacetophenone can also be obtained by so-called Friedel-Crafts type reaction of phenol with ketene, acetic anhydride, or an acetylating agent such as acetyl chloride. It can be obtained in the same manner by Fries rearrangement after forming phenylacetate with the above acetylating agent. In the above reaction, it is known that 4-hydroxyacetophenone can be obtained in good yield (Organic Reaction Vol. 1, p. 344 (1942), U.S. Pat. No. 4,524,217), and known 4 -It can be manufactured extremely easily and economically as compared with hydroxybenzaldecht.

Further, it is advantageous to use lactic acid as a starting material for the compound of the general formula (1). L (+)-lactic acid and D
(−)-Lactic acid can be obtained from a lactic acid form of lactic acid by a conventional resolution method, or can be obtained from biochemical preparation (Biochemical Preparation).
ion) Volume 3, page 61 (1951), can be directly produced from glucose or the like.

When X is a sulfonyloxy group in the general formula (1), it can be easily obtained by sulfonylating the corresponding optically active lactic acid with various sulfonyl chlorides. When X is a halogen atom, it can be similarly obtained from optically active lactic acid according to the method of French Patent No. 2,459,221. Specific examples of the sulfonyloxy group include a methanesulfonyloxy group, an ethanesulfonyloxy group, a butanesulfonyloxy group,
Aliphatic group-substituted sulfonyloxy group such as trifluoromethanesulfonyloxy group, benzenesulfonyloxy group,
Examples thereof include aromatic group-substituted sulfonyloxy groups such as p-toluenesulfonyloxy group, p-bromobenzenesulfonyloxy group and p-nitrobenzenesulfonyloxy group, and halosulfonyloxy groups such as chlorosulfonyloxy group. Examples of the halogen atom include chlorine atom, bromine atom and iodine atom. Further, in the general formula (1), R means a lower alkyl group, and examples thereof include a methyl group, an ethyl group, a propyne group and a butyl group.

In the first step, the reaction is preferably carried out in the presence of a weak base such as a carbonate such as sodium carbonate, lithium carbonate or potassium carbonate or a bicarbonate such as sodium hydrogen carbonate or potassium hydrogen carbonate. The reaction proceeds even in the presence of a strong base, but if the basicity is too strong, racemization may occur, which is not preferable.

A particularly preferred base in the present invention is potassium carbonate. Further, in order to accelerate the reaction, a phase transfer catalyst as disclosed in JP-A-56-59,718 may be coexistent.

The reaction solvent is preferably an aprotic polar solvent such as dimethylformamide, dimethylsulfoxide and N-methylpyrrolidone, but it is also possible to use acetone, methyl ethyl ketone, acetonitrile, ethyl acetate or the like.

The reaction temperature will vary depending on the solvent used, but may vary from 40 ° C to 120
C., especially 80 to 100.degree. C. are preferred. Reacting at too high a temperature causes lamicization. The reaction time varies depending on the reaction temperature, the presence or absence of a catalyst, the reaction solvent, etc., but it generally takes 1 to 10 hours, preferably 2 to 6 hours. The optically active α-of the intermediate thus obtained
(4-Hydroxyacetylphenoxy) propionic acid ester is a novel substance.

The second step is the above α- (4-acetylphenoxy)
It is a so-called Bayer-Villiger reaction step in the oxidation step of propionic acid ester with peracid. As the peracid used in this reaction, peracids usually used in the Bayer-Villiger reaction such as hydrogen peroxide, peracetic acid, perbenzoic acid, and m-chloroperbenzoic acid can be preferably used. As the reaction solvent in this step,
Various solvents inert to the reaction such as esters such as ethyl acetate, chlorinated hydrocarbons such as chloroform, methylene chloride and carbon tetrachloride, aromatic hydrocarbons such as benzene and toluene can be preferably used. The amount of peracid used in this reaction can be in the range of 1: 1 to 2.0 mol times that of the acetyl compound, and a method of adding this as it is or after dissolving it in an appropriate solvent is suitable. is there. The temperature at the time of addition is appropriately 10 ° C. to 50 ° C., and if necessary, the reaction can be completed by aging for 3 hours to 24 hours. The aging temperature is preferably in the range of 10 ° C to 50 ° C as in the case of addition. The reaction solution thus obtained is inactivated with sodium thiosulfate or the like to inactivate unreacted peracid, and then the product α- (4-acetoxyphenoxy) propionic acid ester is isolated or The reaction crude liquid can be directly subjected to the subsequent solvolysis step without being separated.

The third step is a solvolysis step for acetoxy groups.
This reaction can be achieved by a conventional method using water or alcohols in the presence of acid or alkali. As a catalyst, sulfuric acid,
A catalytic amount of a mineral acid such as hydrochloric acid, an organic sulfonic acid such as p-toluenesulfonic acid, or an alkali such as sodium hydroxide or potassium hydroxide can be used. As the reaction solvent, it is appropriate to use an excess amount of water or alcohols used for solvolysis, but in addition, aromatic hydrocarbons,
Chlorinated hydrocarbons may be added. When alcohol is used, it is preferable to use alcohol (ROH) corresponding to R of the propionic acid ester residue of the general formula (1). The reaction temperature may be in the range of room temperature to the boiling point of the solvent used.

(Effect) By the method of the present invention, it becomes possible to efficiently produce an optically active α- (4-acetoxyphenoxy) propionic acid ester useful as a synthetic intermediate for various optically active phenoxy herbicides.

That is, a novel compound, an optically active α- (, is produced by stereospecific reaction from 4-hydroxyacetophenone which is industrially very easily available at low cost and the optically active propionic acid ester represented by the general formula (1). By selectively obtaining 4-acetylcyphenoxy) propionic acid ester, the problem of the by-product of the bis-substituted compound, which has been conventionally found when hydroquinone is used as a starting material, is solved,
It has become possible to obtain only the desired mono-substituted product in good yield. Furthermore, in the method of the present invention, for example, when peracetic acid is used in the second step, acetic acid by-produced can be recovered, and the acetic acid derivative by-produced by the solvolysis in the third step is recovered to give phenol. Since it can be reused as an acetylating agent, it can be said to be an efficient process for producing the desired α- (4-hydroxyphenoxy) propionic acid ester substantially from phenol and an optically active propionic acid derivative.

Reference example 1. (Production of 4-hydroxyacetophenone) 1 g of phenol was dissolved in 33 ml of acetic anhydride, and several drops of agricultural sulfuric acid was added dropwise, followed by stirring at room temperature for 30 minutes. The reaction solution was added to ice water and extracted with ether. The extract was washed with an aqueous solution of sodium hydroxide and saturated saline, dried over anhydrous sodium sulfate, and then the solvent was removed to obtain 14 g of phenyl acetate. The above phenyl acetate was dissolved in 60 g of nitrobenzene, 10 g of anhydrous aluminum chloride was added little by little, and the reaction solution stirred at room temperature for 20 hours was added to dilute hydrochloric acid and ice to remove nitrobenzene, and the residue was distilled under reduced pressure. , 11 g of 4-hydroxyacetophenone was obtained.

Reference example 2. (Production of methyl S (−)-α (p-toluenesulfonyloxy) propionate) 15.6 g of methyl S (+)-lactate and triethylamine 1
It was dissolved in 5.2 g of methylene chloride (100 ml) and stirred at room temperature. 28.7 g of p-toluenesulfonyl chloride was added to this.
The mixture was added in 0 minutes and stirred at the same temperature for 6 hours. Cold water 100
After adding ml and shaking, the organic layer was separated. The organic layer was washed successively with dilute hydrochloric acid, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and the solvent was removed. The oily residue was distilled under reduced pressure to give the title compound 2
5 g was obtained.

Example 1. (Production of methyl R (+)-α- (4-acetylphenoxy) propionate) 1.0 g of 4-hydroxyacetophenone, S (-)-α
2.1 g of methyl-(p-toluenesulfonyloxy) propionate and 0.6 g of potassium carbonate were added to 30 ml of dimethylformamide and then heated at 95 to 98 ° C for 5 hours. After cooling the reaction solution to room temperature, benzene 100
After adding 100 ml of water and 100 ml of water, the benzene layer was separated and further washed twice with 100 ml of water. The organic layer was dried over anhydrous sodium sulfate, the solvent was removed, and the residue was purified by column chromatography on silica gel to give 1.4.
0 g of the title compound was obtained. (Yield 86%) [α ▲] ²² _D ▼ + 40.35 (C = 1.623 CHCl ₃ ) NMR spectrum (CDCl ₃ , ppm) 1.63 (double line .3H) 2.50 (single line. 3H) 3.70 (single line .3H) 4.80 (quadruple line .1H) 6.80 (double line .2H) 7.80 (double line .2H) Example 2. (Production of methyl R (+)-α- (4-acetylphenoxy) propionate) 1.1 g of methyl R (+)-α- (4-acetylphenoxy) propionate obtained in Example 1 was added to 15 ml of chloroform. Dissolved in, and metachloroperbenzoic acid 1.28
g was added in small portions over 50 minutes. After standing at room temperature for one day and night, the precipitated white crystals were collected by filtration, and the filtrate was washed successively with 1 / 10N sodium thiosulfate aqueous solution, saturated sodium hydrogen carbonate aqueous solution and saturated saline solution, and the organic layer was dried over anhydrous sodium sulfate. did. After removing the solvent, the oily residue was distilled under reduced pressure to obtain 0.82 g of the title compound.
(Yield 70%) [α ▲] ²² _D ▼ + 40.65 ° (C = 1.300 CHCl ₃ ) NMR spectrum (CDCl ₃ , ppm) 1.60 (double line .3H) 2.23 (single line .3H) 3.70 (single line .3H) 4.70 (quadruple line .1H) 6.83 (multiple line .4H) Example 3. Production of methyl R (+)-α- (4-hydroxy) propionate 0.82 g of methyl R (+)-α- (4-acetoxyphenoxy) propionate obtained in Example 2 was added to 30 ml of methanol. The solvent was added, about 0.5 ml of sulfuric acid was added dropwise, and the mixture was heated under reflux for about 6 hours.The solution was added to water and extracted twice with benzene, and the organic layer was washed with saturated sodium hydrogen carbonate and saturated saline. After drying over anhydrous sodium sulfate,
The solvent was removed, and the residue was purified by silica gel column chromatography to obtain 0.51 g of the title compound. (Yield 76%) [α ▲] ²² _D ▼ + 32.22 ° (C = 1.563 CHCl ₃ ) NMR spectrum (CDCl ₃ , ppm) 1.63 (double line .3H) 3.71 (single line .3H) 4.61 (quartet .1H) 5.45 (singlet .1H) 6.68 (singlet .4H) Example 4. Instead of metachloroperbenzoic acid in Example 2, a 30% ethyl acetate solution of peracetic acid was gradually added dropwise. After the reaction, the homogeneous solution was treated with a 1 / 10N sodium thiosulfate aqueous solution and purified in the same manner as in the Example.
Of methyl R (+)-α- (4-acetoxyphenoxy) propionate was obtained. (Yield 80%)

Claims (1)

[Claims] 1. A compound of the general formula of 4-hydroxyacetophenone (In the formula, X is a halogen atom or a sulfonyloxy group,
R means a lower alkyl group. (* Indicates an asymmetric carbon), and after treating the resulting product with peracid,
The optically active α- (4
-Hydroxyphenoxy) propionic acid ester production method.