JPS6281348A - Production of phenylacrylic acid and phenyl-2-hydroxypropionic acid - Google Patents

Abstract

PURPOSE:To obtain the titled compound useful as an intermediate for di cyclopropanecarboxylic acids which are raw materials for insecticides in high yield with little by-products, by reacting a specific compound with chloroform as raw materials in the presence of a basic aqueous solution and phase-transfer catalyst. CONSTITUTION:A compound expressed by formula I (R is H, lower alkyl, lower alkoxy, benzyloxy, halogen atom or phenoxy which may be substituted by lower alkyl, lower alkoxy or halogen) is reacted with chloroform in the presence of a basic aqueous solution, e.g. sodium hydroxide, and at least >=1mol, preferably 1.5-3.0mol, based on the compound expressed by formula I, phase-transfer catalyst expressed by formula II (R' is 1-4C lower alkyl; X is halogen or sulfate) at -10-50 deg.C to give a mixture of the salt-forming compounds expressed by formulas III and IV, which is then acidified and preferably heated to afford the aimed compounds expressed by formulas V and VI.

Description

Detailed Description of the Invention [Field of Industrial Application] The present invention relates to allyl acetic acid derivatives having strong anti-inflammatory effects, and phenyl acrylic acids and phenyl acrylates useful as intermediates for dichlorocyclopropane carboxylic acids used as raw materials for insecticides. -This invention relates to an industrially advantageous artificial method for producing 2-hydroxypropionic acids.

[Prior art] Phenyl acrylic acid of formula (6) below? The method for producing phenyl-2-
The method for producing hydroxypropion e was published in 1987.
-56900 is indicated by X, ).

In the method disclosed in Japanese Patent Publication No. 55-30785, p-isobutylacetophenone and chloroform are reacted under basic conditions in the presence of a catalytic amount of a quaternary ammonium salt to form 2-(p-
(imbutylphenyl)acrylic acid is obtained with a yield of 51.4%.

On the other hand, the method disclosed in Japanese Patent Publication No. 57-56900 involves reacting p-isobutylacetophenone and haloform under basic conditions in the presence of lithium halide and a catalytic amount of quaternary ammonium salt. -Hydroxypropionic acid is obtained with a yield of 65%.

[Problem that the invention seeks to solve]

Conventional methods for producing phenylacrylic acid derivatives or phenyl-2-hydroxypropionic acid derivatives by carbene reaction generally have low yields and produce large amounts of impurities as by-products.
It is difficult to separate and purify and is not industrially advantageous. The method of the present invention produces less impurity by-products (a mixture of phenylacrylic acid derivatives and hyphenyl-2-hydroxypropionic acid derivatives useful for producing allyl acetate derivatives or dichlorocyclopropanecarboxylic acid derivatives) can be quantitatively produced. This provides an industrially advantageous method for obtaining high yields.

[Means for solving problems]

As a result of extensive research into industrially advantageous production methods for phenylacrylic acid derivatives and phenyl-2-hydroxypropionic acid derivatives useful as intermediates for allyl acetic acid derivatives and dichlorocyclopropanecarboxylic acid derivatives, the present inventors found that the formula (In the formula, R represents a hydrogen atom; a lower alkyl group; a lower alkoxy group; a benzyloxy group; a halogen atom, a lower alkyl group, a lower alkoxy group, or a phenoxy group optionally substituted with a halogen atom); Chloroform is added to a basic aqueous solution and less than 1 mole of formula R (2) per formula (]).

The reaction was carried out in the presence of a phase transfer catalyst of the formula (wherein R is as shown below, and X is -, rogene or a sulfate group), and the formula (wherein R is a lower alkyl group, R is the same as above). The present invention was completed by inventing a method for producing a mixture of salt-forming compounds represented by the following formula and then acidifying the mixture to form a free acid.

The present invention will be explained in detail below.

In the reaction of the present invention, the compound of formula (]) and chloroform, preferably 2 to 10 times the mole thereof, are mixed with the compound of formula (1) in a small amount (both 1 mole or more, preferably 1.5 to 3 moles).
．． Preferably in the presence of an aqueous solution containing a 0 molar ratio of phase transfer catalyst, preferably 5 to 20 times the molar base.
Performed at °C. Through this reaction, a mixture of salt-forming compounds of formulas (2) and (3) can be quantitatively produced in the reaction solution. The reaction time is usually completed in 10 to 12 hours. The compounds of formulas (4) and (5) of the present invention are isolated as follows.

After the above reaction, when the reaction solution is allowed to stand, it separates into an organic layer, an aqueous layer, and an inorganic salt layer, and the target products are present in the organic layer in the form of (2) and (3).

This organic layer is separated from the aqueous layer and the inorganic salt layer or not separated from the aqueous layer and the inorganic salt layer, and is made acidic by adding hydrochloric acid or sulfuric acid, heated to room temperature to 100°C, and converted from the compound of formula (1) to the compound of formula (4) and ( Compound 5) can be obtained in high yield.

Next, examples of the basic aqueous solution used in the present invention include aqueous solutions of sodium hydroxide, potassium hydroxide, and the like.

The phase transfer catalysts used in the present invention include benzyltriethylammonium chloride, benzyltriethylammonium bromide, benzyltrimethylammonium chloride, benzyltrimethylammonium bromide, benzyltriethylammonium sulfate, tetragutylammonium bromide, benzyltriethylammonium methyl sulfate, and trioctylmethylammonium chloride. , benzyltributylammonium chloride, tetramethylammonium chloride and the like.

In the present invention, 7 lower 9 means a carbon number of 1 to 8, and... Rogen atom means chloro atom, bromine atom, fluorine atom, or iodine atom? means.

Examples of the compound of formula (1) which is a raw material for compounds of formulas (4) and (5) of the present invention include p-isobutylacetophenone, p-ethoxyacetophenone, p-methoxyacetophenone, p-butoxyacetophenone, m-
Phenoxyacetophenone, m-Cp'-chlorophenoxy)acetophenone, m-(p'-ethoxyphenoxy)acetophenone, p-isopropylacetophenone, p-chloroacetophenone, p-isobutylacetophenone, p-hexylacetophenone, p-benzyloxyacetophenone Examples include.

〔Effect of the invention〕

By the method of the present invention, allyl acetic acid derivatives having an anti-inflammatory effect and phenylacrylic acid derivatives useful as intermediates for dichlorocyclopropanecarboxylic acid derivatives used as intermediates for insecticides and the phenyl-2-hydroxypropionic acid derivatives can be produced industrially. It can be manufactured at low cost and with good yield.

〔Example〕

The present invention will be explained below with reference to Examples, but the present invention is not limited to these Examples.

Example 1 318 g of chloroform, 176 g of I)-isobutylacetophenone, 100 g of water, 250 g of benzyltriethylammonium chloride? Place in a reactor and stir to dissolve. An aqueous solution prepared by dissolving 924 g of potassium hydroxide in 1023 g of water was added dropwise over 10 hours while maintaining the internal temperature at -5 to 0°C.

After the dropwise addition, the mixture was reacted at the same temperature for 2 hours, then 800 g of dichloromethane and 1500 g of water were added, and the mixture was allowed to stand still for liquid separation to separate the organic layer. Is the separated organic layer acidified with hydrochloric acid and catalyzed? After separation, it is washed with water and concentrated under reduced pressure. Obtained solid substance 2
Recrystallize from 80 g of 70% methanol water, filter and wash,
After drying, 214 g'i of white crystals were obtained. As a result of gas chromatography analysis, 2-(p-isobutylphenyl/L/
acrylic acid and 2-(p-isobutylphenyl)-
The production ratio of 2-hydroxypropionic acid was 4:6.

Reference Example 214 g of the product of Example 1 was dissolved in 2000 ml of 7 equimolar sodium hydroxide aqueous solution, 20 g of Raney nickel was added, and the mixture was reduced at 40° C. under a hydrogen pressure of 10 kg/Cm. After filtering the catalyst, it is acidified to 2-(p-isobutylphenyl).
196 g of propionic acid (total yield from p-isobutylacetophenone=95%) was obtained. The physical properties of this product were as follows.

Molecular formula C13H1802 Elemental analysis value C,75,61%H88,72%0,15
．． 67%l Calculated value C, 75, 69%H, 8, 80% 0
, 15.51% infrared absorption spectrum 2960crn
1715crn 1230m Melting point 75-77
°C Example 2 p-Inbutylacetophenone 120g (0.68 mol), triethylbenzylammonium chloride 340
g (0,68X2.2) to 21.5 g (0
, 68
was added, and 1126 g of a 47% potassium hydroxide aqueous solution (0.68X]4) was added dropwise over 10 hours while maintaining the liquid temperature at -5 to 5°.

After dropping and reacting at the same temperature for 5 hours, 000 g of dichloromethane was added, stirred well, and separated. The separated dichloromethane layer was treated with 35% hydrochloric acid to make it acidic and remove triethylbenzylammonium chloride. The dichloromethane layer was washed with 1,000 ml of water, then concentrated under reduced pressure, and the resulting solid was recrystallized from 80 g of 70% methanol water, filtered, washed, and dried to obtain 146 g of white crystals. (Rough coating rate 100%) As a result of gas chromatography analysis, the production ratio of 2-(p-inbutylphenyl)acrylic acid and 2-(1)-isobutylphenyl)-2-hydroxypropionic acid was 5.
．． The ratio was 5:4.5.

Hydrogen reduction was carried out in the same manner as in the reference example of Example 1, catalyst Y was acidified after filtration, and 136.4 g of 2-(p-inbutylphenyl)propionic acid (total yield from p-isobutylacetophenone was 97%). %) was obtained. Moreover, the melting point of this product was 755-77°C.

Example 3 250 g of benzyltriethylammonium chloride,
Add 100g of water to the reactor and stir to dissolve. Internal temperature -
5~] 55% potassium hydroxide aqueous solution 1 while keeping at 0℃
A solution prepared by dissolving 020 g of p-ethoxyacetophenone and 164 g of p-ethoxyacetophenone in 358 g of chloroform was simultaneously added dropwise over 5 hours. After dropping, the mixture is allowed to react at the same temperature for 2 hours. The generated potassium chloride is taken from house to house, the filtrate is allowed to stand, the liquid is separated, and the organic layer is extracted. Separate. Potassium chloride in chloroform 30
Wash with 0 g and combine the washing liquid with the previous organic layer.

The entire organic layer is washed with 400 g of 25% hydrochloric acid water to remove benzyltrimethylammonium chloride. The separated organic layer was washed with dilute hydrochloric acid and water to drive off the organic solvent, and then distilled under reduced pressure to obtain 202 g of the desired mixture (white crystals) having the following structural formula.

As a result of gas chromatograph analysis, formulas (8) and (9)
The production ratio was 7:3.

Claims (4)

[Claims] (1) Formula ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (1) (In the formula, R is a hydrogen atom; a lower alkyl group; a lower alkoxy group; a benzyloxy group; a halogen atom or a lower alkyl group, a lower alkoxy group, or a halogen atom (indicates a phenoxy group which may be substituted with , R indicates the one shown below, and X indicates a halogen atom or sulfate group). There are tables, etc. ▼(3) (In the formula, R represents a lower alkyl group of C_1_ to_4
has the same meaning as above. ) is characterized by obtaining a mixture of salt-forming compounds and then making it acidic ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (4) ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ (5) A method for producing phenylacrylic acid and phenyl-2-hydroxypropionic acid represented by (2) A patent claim in which a mixture of salt-forming compounds of formulas (2) and (3) is extracted with an organic solvent and then made acidic, and the separated phase transfer catalyst is removed to extract the compounds of formulas (4) and (5). The method described in scope item (1). (3) in the presence of an aqueous solution containing 5 to 20 times the mole of a base and a phase transfer catalyst of 1 to 3 times the mole of the compound of formula (1);
A patent claim in which the compound of formula (1) is reacted with 2 to 10 times the mole of chloroform at -10 to 50°C to obtain a mixture of salt-forming compounds represented by formulas (2) and (3), and then acidified. A method for producing phenylacrylic acid and phenyl-2-hydroxypropionic acids represented by formulas (4) and (5) in item (1). (4) in the presence of an aqueous solution containing 5 to 20 times the mole of a base and a phase transfer catalyst of 1 to 3 times the mole of the compound of formula (1);
The compound of formula (1) is reacted with 2 to 10 times the mole of chloroform at -10 to 50°C to obtain a mixture of salt-forming compounds represented by formulas (2) and (3), and then the above-mentioned compound is reacted with an organic solvent. A method according to claim 1, wherein the mixture is extracted and then acidified to remove the separated phase transfer catalyst and to recover the compounds of formulas (4) and (5).