JPS5998033A - Preparation of mandelic acid - Google Patents

Abstract

PURPOSE:To prepare the titled compound useful as an intermediate of agricultural chemicals and pharmaceuticals, without using harmful raw material, in high yield, by reacting glyoxylic acid with benzene in essentially anhydrous state in the presence of a cation exchange resin, and hydrolyzing the reaction product. CONSTITUTION:Glyoxylic acid is made to react with benzen in an essentially anhydrous state in the presence of a cation exchange resin, at 50-80 deg.C, preferably using acetic acid as a cocatalyst. The objective compound can be prepared by hydrolyzing the resultant mandelic acid benzyl ester derivative. The cation exchange resin is preferably a strong acidic cation exchange resin of sulfonic acid type, e.g. Amberlite IR-120B, etc., and its amount is preferably about 50-300wt%, based on glyoxylic acid. The amount of acetic acid used as a cocatalyst is preferably 2-5mol per 1mol of glyoxylic acid.

Description

DETAILED DESCRIPTION OF THE INVENTION Mandelic acid is a chemical substance useful as an intermediate for agricultural chemicals or medicines. However, as a method for producing the acid, a method has long been known in which mandelic acid nitrile, which is obtained by reacting benzaldehyde with hydrocyanic acid, is hydrolyzed with an acid.

However, the necessity of handling hydrocyanic acid, a highly poisonous compound, requires great care in terms of work hygiene and wastewater treatment, and is therefore not desirable as an industrial method.

Therefore, the present applicant proposed a method for industrially advantageous production of mandelic acid without using such harmful raw materials. We proposed a method of reacting glyoxylic acid and benzene in the coexistence of 10 moles. In this method, the yield of mandelic acid is about 6,096 times the yield of glyoxylic acid.

However, the present applicant has now discovered a method for producing mandelic acid with even higher yield and has completed the present invention.

That is, the present invention involves reacting glyoxylic acid and benzene in the presence of a cation exchange resin in a substantially anhydrous state to obtain a benzyl mandelic acid derivative, and then hydrolyzing the derivative to produce mandelic acid. The yield of mandelic acid reaches a maximum of 90% based on glyoxylic acid, and mandelic acid can be obtained extremely efficiently.

The method of the present invention can be expressed as a chemical formula as follows.

Of(C0OHOH) First, in carrying out the present invention, a cation exchange resin is used as a catalyst.

As the resin, a sulfonic acid type strongly acidic cation exchange resin is most advantageously used, but it is also possible to use a weakly acidic cation exchange resin such as a carboxylic acid type or a phosphoric acid type. A specific example of a strongly acidic cation exchange resin is Amberlite 1.
5, Amberlis) XN-10f34.7 n) < -
Light I' R-120B1 Amber Light IR-12
2. Amberlight IR-124, Amberlight IR
C-84 (both Rohm and Haas versions! R),
Dokurite C20, Dokurite Cio, Dokurite CC6 (all manufactured by Chemical Process Co.), Dowex 50WX8, Dowex MSC-1, Dowex CC, R-2 (all made by Dow Chemical Co.), and other Revachit (Bayer Co., Ltd.) (manufactured by National American Corporation), narcite (manufactured by National American Corporation), palmchit (manufactured by Balmchit Corporation), qualphanut (manufactured by Falbenindo Corporation), and 'Diaion (manufactured by Mitsubishi Kasei Corporation). The above-mentioned cation exchange resin having an average pore diameter of about 50 to 100X is particularly advantageously used.

These are used in an amount of about 50 to 600% by weight based on glyoxylic acid.

The reaction must be conducted in substantially anhydrous conditions. Glyoxylic acid is usually sold as an aqueous solution of about 4096 glyoxylic acid, so it is dehydrated and concentrated in advance to obtain glyoxylic acid 1
After forming a hydrate or glyoxylic anhydride, the reaction may be carried out by mixing with excess benzene. Benzene serves both as a raw material and as a reaction solvent.

In addition, when using the aqueous glyoxylic acid solution as it is, it is sufficient to mix the liquid with benzene and once azeotropically dehydrate the benzene and water before starting the reaction.

In any case, in order for the reaction to proceed efficiently, the amount of water in the system must be reduced to 5% by weight or less.

If water is present in an amount greater than the amount required during the reaction, the yield of mandelic acid will be significantly reduced.

Benzene is used in an amount of about 3 to 2 times the molar amount of glyoxylic acid. The reaction temperature is preferably 5° to 80°C and the reaction time is preferably 5 to 50 hours.

Since water is produced as a by-product as the reaction progresses, the reaction is preferably carried out under dehydration.

It is effective to use acetic acid as a promoter during the reaction.

The amount used is 10 mol or less, preferably 2 to 5 mol, per 1 mol of glyoxylic acid.

Particularly, the use of acetic anhydride is advantageous because it also acts as a supplement for aqueous water in the system. If 10 moles or more of acetic acid is used, the reaction rate will decrease and the by-product of Harz will become noticeable.

This reaction produces mandelic acid as an intermediate, and then the derivative is hydrolyzed to give mandelic acid. In the above reaction, benzyl mandelate derivative\/B OOH C20 OH3 c=.

OH3 Both can be converted to mandelic acid by hydrolysis.

Hydrolysis is carried out as follows.

Hydrolysis is possible with either alkaline or acidic (especially cation exchange resins).

In the hydrolysis with an alkali, the cation exchange resin is first separated from the reaction product solution containing the benzyl mandelate derivative obtained in the above reaction. Water is added to the p-liquid, and then alkali hydroxide is added until the pH of the aqueous layer reaches about 11, and when the mixture is heated and stirred for about 1 hour, mandelic acid (alkali salt) is produced. Since this layer is contained in the aqueous layer, the benzene layer is separated from the layer, and an acid such as hydrochloric acid or sulfuric acid is added to the aqueous layer to adjust the pH to 5.
If the temperature is controlled to about ~6, mandelic acid crystals will precipitate. The precipitated mandelic acid is separated from the system by conventional methods such as p-filtration and centrifugation, washed with a small amount of cold water, and dried to obtain a final product. If necessary, purification operations such as recrystallization are carried out as appropriate.

On the other hand, acid hydrolysis can also be carried out using mineral acids such as sulfuric acid and hydrochloric acid, but the catalyst for the reaction between benzene and glyoxylic acid can be used as it is as a catalyst for hydrolysis, and the catalyst can be easily recovered. In this respect, the use of cation exchange resins is advantageous. To carry out hydrolysis using a cation exchange resin, benzene may be distilled off from the reaction product solution containing the mandelic acid derivative, and then water may be added to the thread and heated. When removing benzene, if there is a risk of deterioration of the cation exchange resin, first remove the catalyst from the reaction product liquid, distill off the benzene, then add water and the cation exchange resin to hydrolyze it. It's okay.

After the hydrolysis is completed, the cation exchange resin is separated and the p solution is cooled. Mandelic acid precipitates out and is isolated according to a conventional method.

The mandelic acid thus obtained is useful as an intermediate for pharmaceuticals and agricultural chemicals.

Next, Ryoaki Ki's method will be explained in more detail using an example.

Example 1 50 with stirrer, thermometer and decanter 1 cooling pipe
0 me glyoxylic acid monohydrate in a four-loaf flask.
．． 1 mole, 2 moles of benzene, 1 mole of acetic acid, and Hirebatit 5PC118BG (manufactured by Bayer, cation exchange resin)
100p was charged and the reaction was carried out at 80° C. for 24 hours with stirring and dehydration to obtain a Man C-〇H3 product solution.

After washing the cation exchange resin door-to-door with benzene,
The cleaning solution and p solution were mixed.

500 g of water was added to the mixture, and a 40% aqueous sodium hydroxide solution was added while stirring until the pH of the aqueous layer reached 11. Thereafter, a hydrolysis reaction was carried out at room temperature for about 60 minutes.

The aqueous layer and benzene layer were separated, and hydrochloric acid was added to the aqueous layer until the pH became 1 or less to precipitate crystals of mandelic acid. The yield of mandelic acid based on glyoxylic acid was 80%.

After recrystallization, the melting point and IR spectrum of the obtained mandelic acid were compared with those of the standard product, and it was confirmed that they matched.

Example 2 0.4 mol of glyoxylic anhydride and 2 mol of benzene,
0.2 mol of acetic anhydride and Revatit 5PC118BG5
0y was placed in the same flask as in Example 1 and heated at 75℃ for 24 hours.
A time reaction was performed.

After that, hydrolysis was performed in the same manner as in Example 1 to 80%
Mandelic acid was obtained in a yield of .

Example 6 In the same flask as in Example 1, 1 mol of glyoxylic acid, 5 mol of acetic acid, 10 mol of benzene, and 5 PC of levacit.
I18G150y was charged and azeotropic dehydration reaction was carried out for 24 hours.

The cation exchange resin was separated from the reaction-completed solution, and the P solution was distilled under reduced pressure to remove acetic acid and benzene.

100 y of water was added to 120 y of the obtained concentrated solution, and 100 y of Diaion 5K-IBH (cation exchange resin, manufactured by Mitsubishi Kasei Corporation) was added thereto, and a hydrolysis reaction was carried out at 80° C. for 8 hours. After the reaction was completed, the cation exchange resin was removed from door to door and the P solution was cooled to 15°C.

After concentrating the p solution from which the precipitated diphenylacetic acid had been separated, it was cooled again to 15° C., and mandelic acid crystals were precipitated. The yield was 90%.

Claims (1)

[Claims] 1. A method for producing mandelic acid, which comprises reacting glyoxylic acid and benzene in the presence of a cation exchange resin in a substantially anhydrous state to obtain a benzyl mandelic acid derivative, and then hydrolyzing the derivative.