Preparation Of D-Hydroxyphenylglycine By Asymmetric Transformation

Single isomer was obtained economically and effectively by asymmetric transfor-maormation. Owing to the non-equivalent isomers in the process, chemical resolution and racemization happened at the same time in solution. Asymmetric transformation breaks through the limit yield of chemical resolution(50%). Resolving efficiency was greatly improved. Asymmetric transformation is easy to operate with low carbon and little pollution. It meets the development direction of green chemistry and the demand of requirement of sustainable developments.D-Hydroxyphenylglycine(D-HPG) is an important pharmaceutical intermediate. There is a large damand in domestic and international market. Currently industrialized production of D-HPG was depended on classical chemical resolution with low resolving efficiency and low optical purity product. D-HPG produced by asymmetric transformation is still not practiced in industry. In this paper, based on a large number of references, D-HPG was prepared by asymmetric transformation with (+)-1-phenylethanesulfonic acid ((+)-PES) as chiral reagent. It was very important in theoretical and in practical to prepare D-HPG by asymmetric transformation.(+)-PES is a strong acid resolving reagent with a rigid structure of benzene ring. Beacause of difficult synthesis and purification process, (+)-PES was not available in domestic and international market.Emphasises of this paper are synthesis of (+)-PES and preparation of D-HPG by asymmetric transformation.PES were prepared via reduction reaction, halogenation reaction, substitution reacti-on and oxidation reaction from starting material acetophenone, and the total yield was 73.1%. This method was easy to operate, with low cost, producing high yield and high optical purity. It not only avoided unpleasant odor of thiol, but also avoided more purif-ycation process of 1-phenylethanesulfonid acid via sodium sulphite substitution; it is a method for industrial production of PES.Chiral PES was prepared by chemical resolution with D-HPG as resolution reagent. (+)-PES·D-HPG and (-)-PES·D-HPG salt was obtained from reaction of D-HPG and (±)-PES in water. Diastereoisomers were dissolved in water then 5% sodium hydroxide solution was used to adjust solution pH, (+)-PES and (-)-PES were obtained and (+)-PES (99%e.e.) was got with the yield of 93%. Another focus of this paper is preparation of D-hydroxyphenylglycine by asymm-etric transformation with (+)-PES as chiral reagent. The influencing factor of asymmetric transformation process were studied such as resolvent, catalyst, solid to liquid ratio, temperature, and stirring way. The better condition for preparation of D-HPG·(+)-PES (99.6%e.e.) with yield of 86.1% was as follows:the equivalence of DL-HPG, PES and salicylaldehyde is 1:1:0.2 in water, solid to liquid ratio at 1:3, mechanical stirring for 11h at 90℃. Preparation of D-HPG from D-HPG-(+)-PES salt was also studied in this paper. D-HPG·(+)-PES was dissolved in water, the solid to liquid ratio at 1:1.5, mechanically stirring with 5% sodium hydroxide solution adjusting pH to 5.41, then filteration, D-HPG (99.4%e.e.) was obtained with the yield of 99%. The chiral reagent (+)-PES can be recycled for use.Structure of (+)-PES was determined by UV, IR,1HNMR, CSP-HPLC, and MS. Spectra showed the structure of (+)-PES was correct, with a high optical purity more than 99%e.e.. Structure of D-HPG was determined by IR and CSP-HPLC, results show that preparation of D-HPG by asymmetric transformation has correct structure and high optical purity 99.4%e.e..PES was prepared via reduction reaction, halogenation reaction, substitution reaction and oxidation reaction from starting material acetophenone. This method is easy to operate, low cost, low carbon and little pollution, which is not found in references, and it is an important innovation of paper.In addition, asymmetric transformation for preparing D-HPG in water was also not found in references and this is also an important innovation of this paper.