Novel synthesis process of DL-p-hydroxyphenylglycine

Abstract

The invention relates to a novel synthesis process of DL-p-hydroxyphenylglycine (DL-HPG), and belongs to the field of pharmaceutical and chemical intermediate production. A purpose of the invention is realized by that: under the effect of a phase transfer catalyst quaternary ammonium salt, phenol, glyoxylic acid, water, and 4-nitro-phthalimide are subjected to a one-pot reaction; the material is cooled to 25 DEG C, and is filtered, such that 4-nitro-phthalic acid solid is obtained; a filtrate is cooled in ice water, and is subjected to pump filtration; a filter cake is sequentially washed by using ice water and ethanol, until the filter cake is colorless; the filter cake is dried, such that a white powdery DL-HPG product is obtained; a mother liquor with main components of glyoxylic acid and the phase transfer catalyst is subjected to reduced-pressure distillation concentration, and is used for replacing partial raw material in DL-HPG synthesis. The process provided by the invention overcomes defects of the productions of large amounts of ammonia-nitrogen, strong acids and phenolic wastewater of current DL-HPG synthesis methods. With the process provided by the invention, a byproduct 4-nitro-phthalic acid is easy to separate and recover, excessive glyoxylic acid and phase transfer catalyst can be recycled, wastewater amount is low, and wastewater is easy to process.

Description

technical field [0001] The technical field described in the present invention is the production field of pharmaceutical and chemical intermediates, and is about the preparation technology of compounds with the following structure: [0002] [0003] The chemical name is DL-p-hydroxyphenylglycine (abbreviated as DL-HPG). It is a racemic mixture obtained through chemical synthesis. , cefadroxil, cefoperazone, cefuroxime and cefadroxil and other drugs essential side chain acid. Background technique [0004] Synthesis technology of D-HPG Synthesis methods can be roughly divided into two categories, one is biosynthesis, and the other is chemical synthesis. Due to its advantages in raw materials, cost, production cycle and mature technology, chemical synthesis is currently the main method for producing D-HPG. Chemical synthesis methods at home and abroad tend to synthesize racemized DL-HPG first, and then split to obtain D-HPG. The methods for synthesizing DL-p-hydroxyphenylgl...

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Problems solved by technology

Chemical synthesis methods at home and abroad tend to synthesize racemized DL-HPG first, and then split to obtain D-HPG. The methods for synthesizing DL-p-hydroxyphenylglycine at home and abroad are: (1) Strerker amino acid synthesis method, That is to use p-hydroxybenzaldehyde and cyanide to generate p-hydroxy-α-aminophenylacetonitrile, and then acid hydrolyze to generate the target compound. This method is relatively mature, but it uses expensive p-hydroxybenzaldehyde and highly toxic cyanide, which is environmentally friendly. Very high, has been phased out

(2) Use glyoxylic acid and phenol to react to generate p-hydroxymandelic acid, and then ammonolysis to generate the target compound. This method needs high-speed stirring in the condensation reaction, and the post-treatment is complicated

(3) Use glyoxylic acid, urea and phenol to generate p-hydroxyphenylhydantoin, and then hydrolyze to obtain the target compound. The raw materials of this method are easy to get and cheap, but the reaction time is long and the yield is not high

(4) Glyoxylic acid-phenol-ammonium salt one-step synthesis method It is a new process developed at home and abroad in recent years, which uses glyoxylic acid, phenol and ammonium salt to synthesize DL-p-hydroxyphenylglycine in one step. Easy to get, cheap, yield up to 61.0%, but difficult to deal with a large amount of ammonia nitrogen, strong acid and phenolic waste water in production

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