JPH0224263B2 - - Google Patents

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 toxic 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 first proposed a method for industrially advantageous production of mandelic acid without using such harmful raw materials, in which sulfuric acid is present in the presence of 0.1 mole or more and less than 1 mole and acetic acid 0.5 to 10 mole per mole of glyoxylic acid. proposed a method for reacting glyoxylic acid and benzene. In this method, the yield of mandelic acid is about 60% based on 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 is up to 90% of that of glyoxylic acid, and mandelic acid can be obtained extremely efficiently. The chemical formula of the method of the present invention is as follows. First, when 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. Specific examples of strongly acidic cation exchange resins include Amberlyst 15 and Amberlyst.
XN-1004, Amberlite IR-120B, Amberlite IR-122, Amberlite IR-124, Amberlite IRC-84 (all manufactured by Rohm and Haas), Dowlite C20, Dowlite
C10, Dowex CC3 (all manufactured by Chemical Process Co., Ltd.), Dowex 50WX8, Dowex
MSC-1, Dowex CCR-2 (all manufactured by Dow Chemical Company), Revacit (manufactured by Bayer), Narcite (manufactured by National American Company), Palmtit (manufactured by Palmtit), Wolfachit (manufactured by Falbenindo), Examples include Diamondion (manufactured by Mitsubishi Kasei Corporation). The above-mentioned cation exchange resins having an average pore diameter of about 50 to 1000 Å are particularly advantageously used. These are used in an amount of about 50 to 300% by weight based on glyoxylic acid. The reaction must be conducted in substantially anhydrous conditions. Glyoxylic acid is usually sold as a 40% aqueous solution, so it can be dehydrated and concentrated to form glyoxylic acid monohydrate and glyoxylic anhydride, and then mixed with excess benzene to carry out the reaction. . 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 more water than this amount is present during the reaction, the yield of mandelic acid will drop significantly. Benzene is used in an amount of about 3 to 20 times the molar amount of glyoxylic acid. Reaction temperature is 50-80
℃, 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 cocatalyst during the reaction. The amount used is 10 mol or less, preferably 2 to 5 mol, per 1 mol of glyoxylic acid. In particular, the use of acetic anhydride is advantageous because it also acts as a co-stimulant for water in the system. If more than 10 moles of acetic acid are used, the reaction rate will decrease and Harz by-products will become noticeable. Such a reaction produces a benzyl mandelate derivative as an intermediate.

[Formula] is generated. The derivative is then hydrolyzed to mandelic acid. In the above reaction, in addition to the benzyl mandelate derivative,

[Formula] or vinegar In the presence of acid

[Formula] or etc., which can all 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 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 liquid, and then alkali hydroxide is added until the pH of the aqueous layer reaches about 11. Mandelic acid (alkali salt) is produced by heating and stirring for about 1 hour. Since the salt is contained in the aqueous layer, this layer is separated from the benzene layer,
When an acid such as hydrochloric acid or sulfuric acid is added to the aqueous layer to control the pH to about 5 to 6, mandelic acid crystals are precipitated. The precipitated mandelic acid is separated from the system by conventional methods such as filtration and centrifugation, washed with a small amount of cold water, and dried to obtain the 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 there are some advantages such as the fact that the reaction catalyst of benzene and glyoxylic acid can be used as it is as a hydrolysis catalyst, 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 a mandelic acid derivative, and then water may be added to the system 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, and 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 liquid is cooled to precipitate mandelic acid, which is then isolated using a conventional method. The mandelic acid thus obtained is useful as an intermediate for pharmaceuticals and agricultural chemicals. Next, the method of the present invention will be explained in more detail by giving examples. Example 1 In a 500 ml four-necked flask equipped with a stirrer, a thermometer, a decanter, and a cooling tube, 0.1 mol of glyoxylic acid monohydrate, 2 mol of benzene, 1 mol of acetic acid, and Levacit SPC118BG (manufactured by Bayer, cation exchange resin) were added. ) 100g and stirred at 80℃ for 24 hours.
Mandelic acid benzene derivatives are obtained by performing the reaction under dehydration for a long time. A reaction product liquid was obtained. After the cation exchange resin was separated and thoroughly washed with benzene, the washing liquid and the liquid were mixed. 500 ml 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 30 minutes. Separate the aqueous layer and benzene layer and add hydrochloric acid to the aqueous layer until the pH is 1.
The amount of mandelic acid was added to precipitate crystals of mandelic acid. The yield of mandelic acid based on glyoxylic acid was 80%. In addition, the obtained mandelic acid has a melting point and a
This was confirmed by comparing the IR spectrum with the standard product and finding a match between the two. Example 2 0.4 mol of glyoxylic anhydride and 2 benzene
mol, acetic anhydride 0.2 mol and rebatit
50 g of SPC118BG was placed in the same flask as in Example 1, and the reaction was carried out at 75°C for 24 hours. Thereafter, hydrolysis was carried out in the same manner as in Example 1 to obtain mandelic acid with a yield of 80%. Example 3 Into the same flask as in Example 1, 1 mole of glyoxylic acid, 3.5 moles of acetic acid, 10 moles of benzene, and 150 g of Rebachito SPC118G were charged, and an azeotropic dehydration reaction was carried out for 24 hours. Separate the cation exchange resin from the reaction finished solution,
The liquid was distilled under reduced pressure to remove acetic acid and benzene. 100 g of water was added to 120 g of the obtained concentrate, and 100 g of Diaion SK-IBH (manufactured by Mitsubishi Kasei Corporation, cation exchange resin) was added thereto, followed by a hydrolysis reaction at 80° C. for 8 hours. After the reaction was completed, the cation exchange resin was removed and the liquid was cooled to 15°C. After concentrating the liquid from which the precipitated diphenyl acetic 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 a substantially anhydrous state in the presence of a cation exchange resin to obtain a benzyl mandelic acid derivative, and then hydrolyzing the derivative.