www.aasraw.com
6.9 Hz, 3H). In order to screen the influence of the different reaction medium’s components, enzymes, solvent, acyl donor and temperature were evaluated. A 20 μL aliquot was transferred to a new vial and 980 μL of ethyl acetate was added and analyzed in the GC-FID. Dynamic kinetic resolution (DKR) reactions in continuous flow
Continuous flow experiments were performed using an Asia Flow System (Syrris) which included a syringe pump, a heater and a glass column. The glass column was packed with immobilized CAL B and VOSO4.XH2O alternately. A 10 mL-packed-bed reactor with 4 layers of enzyme (each layer containing 500 mg of the catalyst) and 3 layers of VOSO4.XH2O (each layer containing 500 mg of the catalyst) separated by thin cotton layers was obtained. The bed-packed reactor was heated at 80 °C and perfused with isooctane at a flow rate of 1.0 mL.min?1. Continuous flow reactions were carried out by pumping a isooctane solution (15 mL) of 1-(2,6-dichloro-3-fluoro-phenyl)-ethanol (0.1 M) and vinyl acetate as acyl donor (0.1 M) through the bed-packed reactor at flow rates of 0.1, 0.5 and 1.0 mL.min?1, which correspond to residence times of 100, 50 and 10 min, respectively. Due to the long reaction time in batch, the solution was recycled in the continuous flow to optimize the conversion results. Aliquots of 20 μL were collected from the output of the reactor after pumping the reactional solution for two times the residence time and after 21 h. Afterwards, the aliquots were diluted with ethyl acetate to 1.0 mL solution and analyzed by GC-FID. Chromatography analysis
Kinetic Resolution and Dynamic Kinetic Resolution 1-(2,6-Dichloro-3-fluorophenyl)-ethanol GC-FID: (Shimadzu CG2010 – chiral capillary column Gamadex – 225) 8 μL samples were injected at 117 °C. The oven was heated at 2 °C/min to 150 °C then maintained for 5 min and at 30 °C/min to 200 °C and then maintained for 1 min, with a 3.0 mL/min flow, and a Split injection mode (Ratio: 20:1). Results and discussions
Based on our previous experience on kinetic resolutions of sec-phenylethanol derivatives, we have learned along these years that ortho-substituted aryl alcohols are less reactive for the kinetic resolution. Since 1-(2,6-dichloro-3-fluorophenyl)ethanol (2) contains substituents on both ortho positions, we were expecting long reaction times for this transformation. We have started by screening the influence of acyl donor on the reaction outcome when using commercial immobilized CAL B (N435) at 60 °C and cyclohexane as solvent for 10 days (Table 1). Acyl donor evaluation for kinetic resolution of 1-(2,6-dichloro-3-fluorophenyl)ethanol (2) mediated by immobilized CAL-B. 5
AASraw Biochemical Technology Co.,Ltd aas14@aasraw.com
