Insight into microwave irradiation and enzyme catalysis in enantioselective resolution of RS‐( ± )‐methyl mandelate

Abstract

AbstractBACKGROUND:Mandelic acid enantiomers are important chiral analogs used for the resolution of racemic alcohols and amines. R‐(−)‐mandelic acid is a precursor for the production of semi‐synthetic penicillins and cephalosporins and also for the synthesis of various pharmaceuticals. Production of optically pure mandelic acid enantiomers is commercially significant. This work deals with the resolution of RS‐( ± )‐methyl mandelate to produce optically pure R‐(−)‐mandelic acid in non‐aqueous media via lipase‐catalyzed hydrolysis under microwave irradiation.RESULTS:Among three commercial lipases, Novozym 435 (Candida antartica B immobilized on macroporous polyacrylate resin) was found to be the most effective in the selective hydrolysis of R‐(−)‐methyl mandelate to R‐(−)‐mandelic acid from the racemic mixture of RS‐( ± )‐methyl mandelate, with an optical purity (eep) of 84.2% after 4 h at 50 °C. The effects of various parameters were studied to arrive at the optimum parameters and kinetics. The optimum catalyst loading was found to be 5 mg cm−3 at a concentration of 0.25 mmol cm−3 each of methyl mandelate and water. Based on the initial rate studies and concentration profiles, a complete rate equation is proposed, which includes the irreversible inactivation caused by RS‐( ± )‐methyl mandelate, and it follows the ternary complex mechanism with dead end inhibition by RS‐( ± )‐methyl mandelate.CONCLUSION:Novozym 435 is the most active lipase for resolution of R‐(−)‐mandelic acid from RS‐ ( ± )‐methyl mandelate in tert‐butanol. Various equilibrium constants were evaluated and simulations were performed giving excellent agreement between the two. Copyright © 2008 Society of Chemical Industry