JPH0610153B2 - Process for producing optically active 2- (4-hydroxyphenoxy) propionic acid - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION [Field of Industrial Application] The present invention provides an optically active 2- (4-hydroxyphenoxy).
The present invention relates to a method for producing propionic acid.

2- (4-Hydroxyphenoxy) propionic acid is described in JP-A-56-16475 (or British Patent Publication GB204253).
9B), JP-A-54-22371, JP-A-53-40767 and the like, which are useful compounds as intermediates for excellent herbicides.

More importantly, since these herbicides having 2- (4-hydroxyphenoxy) propionic acid as an intermediate have an asymmetric carbon atom in their structure, there are two types of optically active compounds. It is known that one of the d-forms has a strong herbicidal activity (for example, JP-A-56-553).
No. 72). Therefore, if only an optically active substance having a strong herbicidal activity is used as a herbicide, the required dosage is almost half that of the racemate, which not only protects the environment and saves resources but also manufactures herbicides and herbicides. It is significant that the cost of spraying can be reduced.

[Conventional technology]

As a conventional technique for producing optically active 2- (4-hydroxyphenoxy) propionic acid, a method described in JP-A-59-95237 (hereinafter referred to as conventional method A), that is, optically active 2-halopropion There is a method of condensing an acid and hydroquinone in an aqueous alkaline solution. Further, as a conventional technique for producing esters of optically active 2- (4-hydroxyphenoxy) propionic acid, West German Patent Publication
There is a method described in GODE3150233 (hereinafter referred to as conventional method B), that is, a method of condensing an optically active 2-halopropionic acid ester and hydroquinone in the presence of DMSO solvent and calcium hydroxide.

[Problems to be solved by the invention]

The above-mentioned patent relating to the conventional method A includes the optically active 2- (4-
The results are unknown because there is almost no specific description of the production method and physical properties of hydroxyphenoxy) propionic acid.

In the conventional method B, it is difficult to avoid partial racemization that occurs during the reaction, even though an expensive optically active material such as optically active n-butyl 2-chloropropionate is used. It is not possible to obtain an alkyl ester of 2- (4-hydroxyphenoxy) propionic acid with high optical purity. (Example 3 of GODE3150233 shows optically active 2- (4-hydroxyphenoxy) propionic acid n
-There is an example of the production of butyl, and there is a description of the optical rotation of ▲ [α] ²⁵ _D ▼ + 11.8 °, but of the optically active 2- (4-hydroxyphenoxy) propionate n-butyl produced by the present inventor. Compared with the value, ▲ [α] ²⁵ _D ▼ + 57.6 ° (neat), it is clear that racemization is apparently occurring.

Further, as a problem common to the conventional methods A and B, a large amount of a compound in which two hydroxyl groups of hydroquinone are both alkylated produces a byproduct, resulting in a low yield, and an expensive optically active material is required more than necessary. There is a problem that must be used.

In other words, what is technically required is to produce 2- (4-hydroxyphenoxy) propionic acid with high optical purity and to obtain a mono-substituted hydroquinone with high selectivity. Unless these two problems are solved, it cannot be used as an industrial manufacturing method.

[Means for Solving Problems and Aspects of the Invention]

The present inventors have found that optically active 2- (4-hydroxyphenoxy)
As a result of diligent research on an industrial production method of propionic acid, a method for easily obtaining 2- (4-hydroxyphenoxy) propionic acid having high optical purity by a method shown below with high selectivity without using a special apparatus Established.

Specifically, the optically active α-halopropionic acid alkali metal salt is dissolved in methanol or ethanol and reacted with hydroquinone or an alkali metal salt of hydroquinone in the presence of an alkali metal hydroxide or an alkali metal alkoxide.

Optically active α-halopropionic acid alkali metal salts can be produced from their esters, and by adding esters to an aqueous alkali metal solution to hydrolyze and distilling off the water to isolate it, the optical purity can be obtained without impairing the optical purity. An active α-halopropionic acid alkali metal salt can be obtained. This is used as a methanol or ethanol solution in the reaction. When reacted in an aqueous solution, the selectivity is extremely reduced and a large amount of di-substituted hydroquinone is produced, which is an expensive raw material optically active α-
The alkali metal halopropionate will be wasted.

A chlorine atom or a bromine atom can be used as X in the general formula [I]. Chlorine atom is most preferable in consideration of economy. When producing an alkali metal salt using esters,
In the ester portion, the lower the number of carbon atoms in which a lower alkyl group is used, the better the optical purity. The reaction temperature is preferably 0 to 100 ° C, but most preferably 30 to 70 ° C in consideration of optical purity and selectivity. At the beginning of the reaction, the reaction is performed at a low temperature (eg
By heating (30 to 40 ° C.) and then heating (for example, 60 to 70 ° C.), the optical purity and the selectivity can be increased and the reaction time can be shortened.

Examples of alkali metal hydroxides used for condensation include lithium hydroxide, sodium hydroxide and potassium hydroxide, and examples of alkali metal alkoxides include sodium methylate and sodium ethylate. Sodium hydroxide is most preferable from the viewpoint of.
The amount of the base used is 2 to 10 times mol of hydroquinone, but 2 to 4 times mol is most preferable.

The obtained optically active 2- (4-hydroxyphenoxy) propionic acid is an acid catalyst, specifically hydrochloric acid, sulfuric acid, p-toluene, in an aromatic hydrocarbon solvent such as benzene or an ether solvent such as n-butyl ether. The desired alkyl ester can be converted by carrying out an ester formation condensation reaction while azeotropically dehydrating with an alcohol suitable for the purpose (eg, methanol, ethanol, n-butanol, etc.) in the presence of sulfonic acid and the like. During the esterification reaction, racemization hardly occurs and the three-dimensional structure is maintained. Alcohols used here are practically lower alkyl alcohols such as methanol, ethanol and n-butanol, but are not limited to these.
For example, the reaction proceeds even with alkoxy alcohol, cycloalkyl alcohol, alkenyl alcohol and the like.

[Effects of the Invention] Optically active chloropropionic acid ester or an optically active chloropropionic acid alkali metal salt is reacted with hydroquinone or an alkali metal salt thereof to give an optically active 2- (4-hydroxyphenol) having a high selectivity and a high optical purity. By developing a method for producing enoxy) propionic acid or its esters, 2- (4-heteroalkyloxyphenoxy) propionic acid alkyl ester, which is an active ingredient of an excellent herbicide, is industrially advantageously produced. It has become possible.

[Examples and reference examples]

Hereinafter, the present invention will be described in more detail with reference to Examples and Reference Examples, but the present invention is not limited thereto.

Example 1 85.8 g of methyl α-chloropropionate was added dropwise at 20 to 40 ° C. into an aqueous solution containing 28 g of sodium hydroxide and 150 g of water. After the dropping, water was distilled off under reduced pressure to obtain a white solid. This was dissolved in 300 g of ethanol to obtain an ethanol solution of -α-sodium chloropropionate.

110g of hydroquinone and 100g of sodium hydroxide at 40 ℃
After stirring for an hour, an ethanol solution of sodium -α-chloropropionate was added and the mixture was heated to 60 ° C. After reacting for 2 hours, 100 g of hydrogen chloride gas was blown in to generate sodium chloride by filtration, and 300 g of benzene was added to the filtrate to carry out azeotropic dehydration for ethyl esterification. After the solvent was distilled off, the residue was washed with water to remove hydroquinone and then distilled to obtain 130 g of ethyl d-2- (4-hydroxyphenoxy) propionate. Optical purity is 93% as measured by liquid chromatography
It was ee. The amount of di-substituted product was 6.5 g.

Example 2 The ethanol solvent of Example 1 was changed to methanol for reaction. After distillation, 110 g of methyl d-2- (4-hydroxyphenoxy) propionate was obtained. The optical purity was 93% ee as measured by liquid chromatography. The amount of di-substituted product was 10 g.

Example 3 85.8 g of methyl -α-chloropropionate of Example 1 was replaced with 95.6 g of ethyl -α-chloropropionate and reacted. After distillation, 131 g of ethyl d-2- (4-hydroxyphenoxy) propionate was obtained. The optical purity was 90% ee as a result of measurement by liquid chromatography. The amount of di-substituted product was 6 g.

Reference example 1 2,6-dichloroquinoxaline 3.98 g, d-2- (4-
Hydroxyphenoxy) ethyl propionate {▲ [α]
²⁵ _D ▼ + 42.5 ° (C = 1.14, chloroform), optical purity
93% ee} 4.33 g, potassium carbonate 2.76 g acetonitrile 1
9.9g was mixed. The mixture was refluxed for 6 hours with stirring, and then the solvent was distilled off under reduced pressure. The residue was extracted with 100 ml of toluene and 50 ml of water. Take the toluene layer and water 50 ml
After washing twice with, the solvent was distilled off to obtain 7.55 g of a pale yellow solid. This was recrystallized from 11.9 g of ethanol and d-2- [4-
(6-Chloro-2-quinoxalyloxy) phenoxy]
Ethyl propionate (6.45 g) was obtained as colorless crystals. Yield 8
7%. The optical purity determined by NMR analysis using the shift reagent is 9
It was 3% ee.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁵ Identification code Internal reference number FI technical display location C07B 61/00 300 (56) References JP-A-54-19925 (JP, A)

Claims (3)

[Claims] 1. A general formula [I] (In the formula, X represents a chlorine atom or a bromine atom, and M represents an alkali metal atom.), An optically active compound represented by the formula: and a hydroquinone or an alkali metal salt of hydroquinone, and an alkali metal hydroxide or an alkali metal alkoxide. A method for producing optically active 2- (4-hydroxyphenoxy) propionic acid, which comprises reacting in methanol or ethanol in the presence of 2. The production method according to claim 1, wherein X in the general formula [I] is a chlorine atom. 3. The production method according to claim 1, wherein X in the general formula [I] is a chlorine atom and M is a sodium atom.