Clean production method of L-p-hydroxyphenylglycine

Abstract

The invention relates to a clean production method of L-p-hydroxyphenylglycine, which comprises the following steps: reacting phenol and sulfamic acid in an alkane solvent to generate phenol ammonium sulfate, adding a glyoxylic acid aqueous solution with the mass concentration of 50%, carrying out addition reaction with the phenol ammonium sulfate, carrying out azeotropic separation on brought-in water, and after the charging is completed, continuously conducting heating and refluxing for 2-5 hours until the glyoxylic acid is completely converted and the ammoniation reaction is completed; adding deionized water into the reaction liquid, and hydrolyzing reactants to generate DL-p-HPG sulfamic acid double salt; and adding a seed crystal and then conducting cooling to obtain a D-p-HPG sulfamic acid double salt crystal, and further neutralizing the D-p-HPG sulfamic acid double salt crystal by ammonia water to obtain a D-p-HPG product with the content of 99.1%-99.7%, and the molar yield of 60%-64%. The synthesis process and the splitting process of the DL-p-HPG are carried out in one pot, so that the generation of waste mother liquor is greatly reduced. According to the method, the sulfamic acid is used for multiple purposes and serves as a catalyst, an aminating agent and a resolving agent for synthesizing the D-p-HPG at the same time, the raw material cost for preparing the D-p-HPG is reduced, the economical efficiency of the process technology is improved, and the method has industrial application prospects.

Description

technical field [0001] The invention relates to a clean production method of L-p-hydroxyphenylglycine, which belongs to the field of new pharmaceutical and chemical materials. Background technique [0002] L-p-Hydroxyphenylglycine (D-p-Hydroxyphenylglycine, English abbreviation D-p-HPG), chemical name is D-p-hydroxy-α-aminophenylacetic acid, molecular formula is C 9 h 9 NO 3 , molecular weight 167.2, appearance is white flaky crystal, melting point 204°C, slightly soluble in ethanol and water, easily soluble in acid or alkali solution to form salt. [0003] D-p-HPG is mainly used in the production of amoxicillin (amoxicillin), amoxicillin clavulanate, amoxicillin cephalosporin, amoxicillin cephalosporin, cefoperazone, ceftriaxone and other drugs. [0004] At present, glyoxylic acid, phenol and sulfamic acid are mainly used as raw materials in industry to synthesize D-p-hydroxyphenylglycine (DL-p-HPG) first, and then chemically split to obtain D-p-HPG. Although D-p-HPG ca...

AI Technical Summary

Problems solved by technology

However, the experiment found that after the surfactant catalyst was used, the foaming during the product separation process was severe, and the product was difficult to clean, which could not significantly increase the synthesis yield of DL-p-HPG

In addition, the expensive phenylethylsulfonic acid or camphorsulfonic acid resolving agent needs to be recovered and recycled, which is not suitable for use in the presence of high concentrations of impurities and surfactants