JPS6013016B2 - Method for producing 4-hydroxyphenylacetic acid ester - Google Patents

Description

Detailed Description of the Invention The present invention involves hydrogen reduction of 3-chloro-4-hydroxymandelic acid in alcohol to simultaneously perform dechlorination, reduction of the hydroxyl group at the benzyl position, and esterification of the carpoxyl group. The present invention relates to a method for producing 4-hydroxyphenylacetate.

4-Hydroxyphenylacetic acid derivatives are compounds useful as synthetic raw materials for medicines and agricultural chemicals.

Conventionally, as a method for producing 4-hydroxyphenylacetic acid derivatives, 3-chloro-4
A method has been proposed for producing 3-chloro-4-hydroxyphenylacetic acid by reducing -hydroxymandelic acid using red phosphorus, tin or stannous chloride. However, this method requires the use of the reducing agent in a stoichiometric amount and is accompanied by operational difficulties when carried out on an industrial scale. Further, Belgian Patent No. 867,28y proposes a method of reducing the sodium salt of 4-hydroxymandelic acid with hydrogen in water in the presence of a palladium catalyst and hydrochloric acid. However, in order to maintain a high yield of the target product in this method, it is necessary to have a 4 to 8 mole excess of hydrochloric acid relative to the raw materials in the reaction system. It is not necessarily advantageous industrially because care must be taken when handling. Therefore, the present inventors conducted intensive studies on a method for producing 4-hydroxyphenylacetic acid derivatives in high yield without using large amounts of reducing agents or corrosive hydrochloric acid, and as a result, arrived at the present invention.

That is, the present invention relates to a method for producing 4-hydroxyphenylacetic acid ester by reducing 3-chloro-4-hydroxymandelic acid with hydrogen in an alcohol in the presence of a palladium catalyst. 3 used in the method of the invention
-Chloro-4-hydroxymandelic acid can be easily obtained, for example, by reacting 2-chlorophenol and glyoxylic acid in the presence of an alkali, or by reacting phenol and glyoxylic acid, followed by chlorination.

The palladium catalyst used in the method of the present invention is prepared by adding metal palladium to a carrier such as activated carbon, graphite, silica gel, calcium carbonate, alumina, etc. in an amount of 0.1 to 1% by weight, preferably 0.5 to 8% by weight. It is appropriate to hold it.

Note that the palladium catalyst is prepared by dissolving palladium chloride in concentrated hydrochloric acid, impregnating the solution into the above-mentioned mortar, and then subjecting the solution to reduction treatment with hydrogen or the like as necessary to remove residual hydrochloric acid. The amount of palladium catalyst used is 3-chloro-
It is preferably 0.001 to 2.0 mm, particularly 0.01 to 0.05 mm, in terms of metal palladium per mole of 4-hydroxymandelic acid. Furthermore, alcohols used in the method of the present invention include methanol, ethanol, 1-propanol 2
-propanol, 1-butanol, 2-butanol, l
Aliphatic alcohols such as so-butanol, 1-bentanol, 2-bentanol, Iso-pentanol, 1-hexanol, 2-hexanol, 1-decanol,
and alicyclic alcohols such as cyclohexanol.

The amount of alcohol used is 0.5 to 10, especially 1 to 10, per mole of 3-chloro-4-hydroxymandelic acid as the raw material.
5 is preferred. As the hydrogen, pure hydrogen or a hydrogen-containing gas mixed with an inert gas such as nitrogen is used.

Hydrogen pressure is 0.1 to 5k9/gauge, especially 1 to 3
kg/gauge is preferred. Also, the reaction temperature is 60~
110:00 o'clock, particularly preferably 70:00 to 90:00 o'clock. The reaction product obtained by the reaction according to the method of the present invention is usually cooled, the palladium catalyst is removed in a furnace, and the alcohol is distilled off from the furnace liquid. The desired product, 4-hydroxyphenylacetic acid ester, is isolated by distilling off the solvent from this extract.

4-hydroxyphenylacetic acid ester is obtained as an ester compound corresponding to the alcohol used in this reaction.

By carrying out the method of the invention, 3-chloro-4
-4-hydroxyphenylacetate can be produced from hydroxymandelic acid in good yield.

Next, examples of the present invention will be shown.

Example 3-Chloro-4-hydroxymandelic acid 10.13 minutes (
50 mmol), 0.2 mmol of 5 wt.
The reaction was carried out for 50 minutes at qo with a light on.

The reaction product was cooled and the catalyst was separated by furnace to obtain a slightly greenish transparent reaction liquid. Unreacted 3-chloro-
4-Hydroxymandelic acid (CHM) was quantified by liquid chromatography, and the produced 4-hydroxyphenylacetic acid ester (HPA) was quantified by gas chromatography. The reaction rate and yield of 4-hydroxycyphenylacetate were calculated. Skin response rate of 3-chloro-4-hydroxymandenoic acid (one of the most important CHM monosynthesis) - (corresponding CHM monosynthesis)

× 100 (Number of moles of CHM charged) 4-hydroxyphenylacetic acid (Number of moles of HPA produced) Yield of ester Phosphorus = (Number of moles of CHM charged) × 100
The results are shown in the table below.

Table *CHM is 3-chlorosan 4-hydroxymandeno acid,
HPA respectively means 4-hydroxyphenylacetic acid ester.

Claims (1)

[Claims] 1. A method for producing 4-hydroxyphenylacetic acid ester, which comprises reducing 3-chloro-4-hydroxymandelic acid with hydrogen in alcohol in the presence of a palladium catalyst.