Optimization of benzoin synthesis in supercritical carbon dioxide by response surface methodology (RSM)

α-Hydroxy ketones are important precursors for biologically active compounds, especially benzoins have important applications in chemistry and pharmacy. In this study enantioselective synthesis of benzoin was studied in supercritical carbon dioxide (SCCO2). Response surface methodology (RSM) was used to investigate the effects of temperature (T), pressure (P) and pH on enantiomeric excess of chiral benzoin using Candida cylindracea lipase in SCCO2. A 23 factorial design was performed to optimize the chiral benzoin synthesis. The optimum conditions were found as 40 °C, 79 bar, pH 6.4 and at these conditions enantiomeric excess (ee) was obtained as 62% (R-benzoin). At the optimum conditions, bases such as DMAP (4-dimethylaminopyridine) and triethylamine were added to reaction medium to increase kinetic resolution. The addition of DMAP considerably enhanced the enantiomeric excess (80% S-benzoin), while triethylamine had negative effect on ee.

Graphical abstractChiral benzoin was synthesized stereoselectively with hydrolysis of benzoyl–benzoin in SCCO2. Experiments were undertaken with CCL (Candida cylindracea) enzyme. Racemic benzoyl–benzoin and enzyme were dissolved in DMSO (dimethyl sulfoxide) and potassium phosphate buffer, respectively, then mixed and put into the SCF reactor. A 23 factorial design was performed to optimize the chiral benzoin synthesis. The optimum conditions were found as 40 °C, 79 bar, pH 6.4 and at these conditions enantiomeric excess (ee) was obtained as 62% (R-benzoin). At the optimum conditions DMAP (4-dimethylaminopyridine) was used to increase kinetic resolution. The addition of DMAP considerably enhanced the enantiomeric excess (80% S-benzoin).Figure optionsDownload full-size imageDownload as PowerPoint slide