Enantioselective Hydrogenation To Synthesize Ethyl (R)-2-Hydroxy-4-Phenylbutyrate

Enantioselective catalytic reaction has received significant attention in recent years because of its potential impact on the synthesis of chiral Pharmaceuticals and other chemicals. Heterogeneous asymmetric catalysis is of special interest for its advantages in separation and reuse of catalysts. In this dissertation, the enantioseletive hydrogenation of ethyl 2-oxy-4-phenylbutyrate (EOPB) to ethyl (R)-2-hydroxy-4-phenylbutyrate (R-EHPB) on Pt catalysts modified by cinchona alkaloid was studied.The modifier, 10,11-dihydrocinchonidine (HCd) was prepared with Pd/C and ethanol was used as the reaction medium. Both conversion and enantiomeric excess (e.e.) were determined by a programmed temperature gas chromatograph with a chiral capillary column.The hydrogenation reaction can be conducted either in a stirred tank batch process, or in a trickle-bed continuous process. When the reactions were carried out in an autoclave, at first the commercial Pt/C was used and the effect of the pre-modified catalysts on hydrogenation results were investigated. It was found that conversion and e.e. both decreased if HCd was pre-adsorbed on catalyst or the catalyst was irradiated by ultrasonic. The e.e.'s were all less than 15% when the hydrogenation was catalyzed with Pt/C in our experiments.5wt% Pt/Al₂O₃ catalyst was prepared with impregnation method and it led to higher optical yields than Pt/C for the asymmetric hydrogenation of EOPB. The influences of some factors on conversion and e.e. were studied. Suitable reaction conditions are as follows: HCd concentration (approx. 0.68mmol.L^-1), initial concentration of EOPB (0.2-0.6mol.L^-1), temperature (333-343K) and hydrogen pressure (5.0MPa).Based on the kinetic feature, the enantioselective hydrogenation mechanism was proposed and the parallel adsorption of HCd via its quinoline ring on Pt surface was considered to be determinative on high enantioselectivity. Different from the asymmetric hydrogenation of ethyl pyruvate, the competitive adsorption between EOPB and HCd was found in our study. According to the mechanism and reasonablepostulations, a hydrogenation rate equation was obtained and it could depict the experimental results well.When a trickle-bed reactor was used, the e.e.'s decreased obviously if the modified Pt/A^Ch was transferred to the reactor. Conversion and e.e. can be kept in steady level when the mixed liquid containing HCd is introduced into the reactor at a constant velocity. In four catalyst beds, the effects of HCd concentration, gas velocity, liquid velocity, pressure and temperature on reaction results were discussed. The e.e. values increase with higher liquid velocity, but conversions are reduced. Higher pressure and temperature both lead to lower optical yields.The productivities obtained in trickle-bed reactor and autoclave were examined. It was found that higher productivities per unit mass of catalyst and per unit volume of reactor were obtained in the autoclave and the trickle-bed reactor, respectively.A partial wetting model was proposed and its simulations of conversion and e.e. were found to agree well with the experimental data in the range of operating conditions studied. In order to evaluate the significance of various parameters used in proposed model, a sensitivity analysis was performed. It was observed that the model was highly sensitive to the values of the effective diffusion coefficient and dynamic liquid-solid mass transfer coefficient.