JPS5852242A - Preparation of hydroxyphenylacetic acid - Google Patents

Abstract

PURPOSE:To prepare the titled compound useful as an intermediate of pharmaceuticals, pesticides, etc., with simple operation, in high yield, by the catalytic reduction of a hydroxymandelic acid, especially 4-hydroxymandelic acid under specific temperature conditions in a lower aliphatic carboxylic acid medium. CONSTITUTION:A hydroxyphenylacetic acid, especially 4-hydroxyphenylacetic acid can be prepared by the catalytic reduction of a hydroxymandelic acid, especially 4-hydroxymandelic acid in a medium comprising a lower aliphatic carboxylic acid, especially preferably acetic acid, etc., in the presence of a palladium catalyst such as Pd/C, at 110-200 deg.C, preferably 120-150 deg.C under the pressure of >=2kg/cm<2>G, preferably >=4kg/cm<2>G for 1-4hr. The amount of the medium is >=3pts.wt., preferably 3-10pts.wt. per 1pt.wt. of the 4-hydroxymandelic acid used as the raw material.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a method for producing hydroxyphenylacetic acid from hydroxymandelic acid, particularly a compound useful as an intermediate for 4-hydroxyphenyl from 4-hydroxymandelic acid. A report has been made.

Isre is also a method for producing 4-hydroxyphenylacetic acid by catalytic hydrogen reduction of 4-hydroxymandelic acid; for example, in JP-A-54-148746,
A method of carrying out catalytic hydrogen reduction in the presence of a large amount of hydrochloric acid at a reaction temperature of 80°C or less is described in JP-A-55-92544, in which a reaction is carried out in the presence of a small amount of mineral acid in a lower aliphatic carboxylic acid medium. A method of carrying out catalytic hydrogen reduction at a temperature of 50 to 100'O is described in Japanese Patent Application Laid-Open No. 56-75455.
Each describes a method for carrying out catalytic hydrogen reduction in the absence of mineral acids in the temperature range from room temperature to 200 T).

The inventors examined these methods and found that ■ is 4-
The yield of hydroxyphenylacetic acid is about 8596,
In addition, corrosion of the reaction equipment is a major problem because a large amount of mineral acid is used, and the quality of 4-hydroxyphenylacetic acid is seriously impaired due to the neutralized salt produced as a by-product. There is also a drawback, and the yield of 4-hydroxyphenylacetic acid is about 80 to 85%, making it difficult to use in practice.
However, it was found that the use of an aqueous medium as described above cannot be said to be industrially advantageous. On the other hand, ■
The method of Fi4-Hydroxyphenylacetic acid reaches a maximum yield of 95%, and is a highly practical method in which corrosion of the reaction equipment is virtually no problem, and the use of a lower aliphatic carboxylic acid medium is replaced by the use of an aqueous medium. Although it is more advantageous, it goes without saying that the higher the tf history c yield is, the more preferable it will be when carried out on an industrial scale.

However, since the yield in this reaction is already 95 g6, it is generally considered difficult to further improve the yield from chemical common sense, but the present inventors dared to take on this challenge and conducted extensive research. As a result, when producing hydroxyphenylacetic acid by catalytic hydrogen reduction of hydroxymandelic acid in a lower aliphatic carboxylic acid medium, 110 to 20 reactions were performed.
It was discovered that hydroxyphenylacetic acid can be obtained almost quantitatively when the process is carried out at a temperature of 0"0, and the present invention has been completed.

The method of the present invention has the following features compared to the conventional method.

(2) By carrying out the catalytic hydrogen reduction reaction at a high temperature of 110υ to 200C, 4-hydroxyphenylacetic acid can be obtained almost quantitatively relative to 4-hydroxymandelic acid. It must be said that it is truly amazing that a quantitative reaction, which is considered difficult in common sense, can be carried out by a relatively simple operation of changing the reaction temperature. As in the present invention, when producing 4-hydroxyphenylacetic acid, 110
Until now, no attempt has been made to improve the yield by carrying out the reaction at a high temperature of 200°C to 200°C, and in fact, both methods (1) and (2) carry out the reaction at a low temperature. In the reduction of 4-hydroxymandelic acid, raising the reaction temperature too high may cause decomposition of the mandelic acid and generation of by-products.
Conventionally, the reaction was mainly carried out at a relatively low temperature, which is not desirable according to common sense, but in the present invention, contrary to common sense, the reaction at a high temperature surprisingly achieves the desired product in good yield. It is true that the reaction in ■ is carried out at a high temperature, but the distinctive feature of ■ is that mineral acids are not allowed to coexist in the system, and the aim is to improve the yield of the target product by controlling the temperature. There is no technical idea to do so.

(2) The above-mentioned effects in the high-temperature reaction are specific and can only be obtained when lower aliphatic carboxylic acids are used as the medium, and such effects cannot be obtained when other media such as aqueous media are used.

■ In the conventional method, a substantially small amount of mineral acid is required as a reaction accelerator during catalytic hydrogen reduction, but in the present invention, the presence of mineral acid causes a significant decrease in yield.
The use of mineral acids must be avoided at all costs.

The method of the present invention will be explained in more detail below.

First, when carrying out catalytic hydrogen reduction, it is necessary to use a lower aliphatic carboxylic acid medium such as acetic acid, propionic acid, butylene, and particularly preferably acetic acid. Efficient reduction cannot be carried out using any other medium. The appropriate amount of the medium to be used is at least 3 times or more, preferably t-1s to 10 times the weight of the raw material 4-hydroxymandelic acid.

The above medium includes a small amount of other medium that does not inhibit the reaction,
For example, water or the like may be added.

It is necessary to limit the reaction temperature to a range of 110 to 200°C. Outside this range, the yield decreases and the effects of the present invention cannot be obtained. Within the above temperature range, 1
It is particularly advantageous to carry out the reaction in the range from 20° to 150°.

The pressure during the reaction varies somewhat depending on the reaction temperature, but is usually 2.
r: I/edG or higher is required. Preferably 4 h/
It is carried out within a range of at least a.

Further, a reaction time F'i of about 1 to 4 hours is required. Examples of catalysts used for catalytic hydrogen reduction include palladium/carbon such as palladium/carbon, Raney Niracle 11 (F) nickel catalyst, and platinum catalyst.

A suitable supporting ratio of the metal catalyst is #io,s~5% by weight. Further, the catalyst is used in an amount of about 5 to 15% based on the weight of the raw material 4-hydroxymandelic acid.

After the reduction is thus completed, the reaction is carried out in a conventional manner (therefore, after removing the catalyst component, the medium is distilled off from the reaction F solution to obtain crystals of 4-hydroxyphenylacetic acid.

If necessary, any purification such as activated carbon treatment or recrystallization in an aqueous medium can be carried out.

According to the present invention, 1 l of 4-hydro-1-xyphenyl vinegar is
It can be obtained quantitatively with a yield of 100% compared to hydroxymandelic acid, and it can be said that its industrial utility value is extremely large.

Next, an example will be given to demonstrate the method of the present invention! This will be explained in detail.

Example 1 60 m of acetic acid, 2OF (86 mmol) of 4-hydroxymandelic acid, and 1 O,S*palladium/carbon were placed in an electromagnetic induction rotating stirring type stainless steel autoclave with an internal volume of 200+4.
．． 6f was supplied. After replacing the interior of the autoclave with nitrogen and further replacing it with hydrogen, the temperature was raised, and the total pressure was controlled to 16'F/jG with hydrogen at a reaction humidity of 130'0. From then on, the above temperature and pressure were maintained while replenishing hydrogen. The reaction was carried out. Hydrogen absorption stopped after 150 minutes.

After the reaction was completed, the autoclave was cooled and the catalyst was separated from the reaction product liquid. The acetic acid medium in the F solution was distilled off under reduced pressure.
．． White crystals of 4-hydroxyphenylacetic acid of 5y were obtained.

The yield based on the raw material 4-hydroxymandelic acid was 99 mol%. Also, the melting point of crystals after re-crystallization from water is I/114
The temperature was 9.5-150.5°C.

Control Example 1 When an aqueous medium was used in place of the acetic acid medium in Example 1, 4
-Yield of hydroxyphenylacetic acid #i was only 82 mol%.

Control Examples 2 to 6 The reaction temperature of Example 1 was 100'0 (Control Example 2), and 2
When the number was changed to 30 (Control Example 5), the yield of 4-hydroxyphenylacetic acid was 68 mol% in Control Example 2 and 23 mol% in Control Example 5.

Examples 2 to 4 The reaction temperature in Example 1 was 125°C (Example 2), 1
When the temperature was changed to 40°C (Example 6) and 145°C (Example 4), the yield of 4-hydroxyphenylacetic acid was 9.
They were 8 mol%, 99 mol%, and 98 mol%.

Examples 5 to 6 A Raney nickel catalyst (however, the amount used was 5 F) was used in place of the palladium/carbon catalyst in Example 1, and the reaction temperature was 15
Reactions were carried out at 0 U (Example 5) and 150'C (Example 6).

The yield of 4-hydroxyphenylacetic acid was 95 mol% in Example 5 and 9'5 mol% in Example 6.

Claims (1)

[Claims] Production of hydroxyphenylacetic acid by catalytic hydrogen reduction of hydroxymandelic acid in a lower aliphatic carboxylic acid medium, characterized in that the reaction is carried out at a temperature of 10C to 200C. Method.