Preparation Of Chiral 1-Phenylethanesulfonic Acid And The Study On Mechanism Of Dutch Resolution

In PES structure, a carbon is a chiral carbon. Because sulfonic acid is a strong acid and benzene ring has rigidity structure, PES has bright prospect as resolving agents. PES can resolve basic compounds, particularly weak base and drugs.In this paper,1-Phenylethanesulfonic acid was prepared via reduction reaction, halogenation reaction, substitution reaction and oxidation reaction from starting material acetophenone. And 1-(4-bromophenyl)-ethanesulfonic acid, 1-(4-Chlorophenyl)-ethanesulfonic acid and 1-(4-nitrophenyl)-ethanesulfonic acid are synthesized via the same way. By using IR, MS, UV and NMR tests, the structures of the acids are all correct.The D-p-hydroxypenylglycine (D-HPG) was used to resolve PES racemates to get (+)-1-PES and (-)-1-PES. (+)-1-PES is up to 99% e.e. with yield more than 89.7%. (-)-1-PES is up to 90% e.e. with yield more than 99%. The recycled yield of D-HPG is more than 92% with enantiomer excess more than 97.5% e.e..Several different family agents with different molar ratios were chosen to resolve p-hydroxyphenylglycine by using (+)-1-PES or (-)-1-PES as parent resolving agents, 1-(4-bromophenyl)-ethanesulfonic acid, 1-(4-chlorophenyl)-ethanesulfonic acid and 1-(4-nitrophenyl)-ethanesulfonic acid as additive agents. Except tenth experiment, Dutch resolution of p-hydroxyphenylglycine and valine by using (+)-l-PES or (-)-1-PES as parent resolving agent got higher optical purity than those of classical resolution.Among the Dutch resolution experiments, levorotatory p-hydroxyphenylglycine with the highest optical purity 99.15% was got by using (+)-1-PES as parent resolving agent with additive 1-(4-bromophenyl)-ethanesulfonic acid. And the ratio of (+)-1-PES to 1-(4-bromophenyl)-ethanesulfonic acid is 92:8. The optical purity value in this experiment is apparently higher than that of classical resolution of p-hydroxyphenylglycine (98.15 %o.p.).Compared to classical resolution, the nucleation tempreture of the less soluble diastereoisomer in Dutch resolution experiments is low, and the metastable zone width is larger by using the (+)-1-PES or (-)-l-PES as parent resolving agent.