Studies On Racemization And Resolution Of P-Hydroxyphenylglycine

DL-p-Hydroxyphenylglycine (DL-p-HPG) , a important medicine intermediate, is resolved to obtain D-p-Hydroxyphenylglycine(D-p-HPG) that is useful for the preparation of amoxicillin, cefopeazone and cefoprozil. Those medicines are widely used and its are more effective than penicillin in antimicrobial capability. The paper studied racemization and resolution of L-p-HPG.Racemization degree of L-p-HPG would be improved with the raise of pH or with the increase of temperature at the same pH in alkaline aqueous solution. The optimal racemization temperature was 95 ℃. L-p-HPG could be racemized in carboxylic acids used as solvents in presence of catalytic amounts of aldehydes. The rate constant of racemization of L-p-HPG was found to follow first-order reaction kinetics. The rate of racemizations was different as carboxylic acids. The water in carboxylic acid decrease the rate of racemization. The study result indicated that a good result could be achieved when the molar ratio of salicylaldehyde to L-p-HPG was 0.1, concentration of acetic acid was above 0.95 and the temperature was 95 ℃. Under such conditions DL-p-HPG was obtained. When the temperature increased, the rate constant of racemization increased. For L-p-HPG, the relation between the rate constant of racemization and its reaction temperature was proposed as follow:k_R = 92042 e -61740/RTPreferential crystallization made use of the solubility difference of D-D-p-HPG and L-p-HPG in water. A number of influence factors to the crystallization were discussed, including crystallizing temperature, temperature of feeding seeds and the ratio of salt to water. The optimal conditions were found as follows: crystallizing temperature, 25℃;w(salt): w(H2O)=1:2.5;temperature of feeding seeds, 30℃;time of crystal formation, 40min, under the conditions, the efficiency of the resolution could be up to 40.83% with 95.8% optical purity.Asymmetric transformation was a resolution method with high quality and performance because racemization and resolution were reacted at the same time. Theappropriate reaction conditions were as following: reaction time was 6h at 95 ℃, filtration temperature was 85 ℃, the content of water was 3% in carboxylic acids, the molar tatio of benzaldehyde to DL-p-HPG was 0.2:1. Under the optimum experimental conditons, the yield and optical purity were 31.15% and 97.3% respectively.The L-p-HPG and D-p-HPG were obtained by treatiing N-acetyl-DL-p-HPG in water using stereoselective aminoacylase as catalyst. A number of influencing factors to the resolution reaction were discussed, including reaction temperature, amount of enzyme, concentration of substance and reaction time. The optimal conditions were found as follows: reaction temperature, 36℃;w(enzyme): w(substrate)=1:26.25;concentration of substance, 0.09mol/L, reaction time, 40h;under the conditions, the efficiency of the resolution could be up to 83.8% with 99.4% optical purity. The method has advantages of high selectability and mild reaction conditions.