| Enantiopure cyanohydrin compounds are useful intermediates in organic synthesis and their derivatives, such asα-hydroxy acids,α-hydroxy ketone andβ-hydroxy amines, are important for the production of Pharmaceuticals and agrochemicals. (S)-α-cyanobenzyl alcohol is one of the most important cyanohydrin. This alcohol is very active and unstable even at room temperature. Therefore, it is a reasonable choice to make it into its ester. Taking use of the compatibility of chemical catalysts and biological catalysts to prepare (S)-α-cyanobenzyl acetate in one pot is the basic idea of this paper.It is necessary to choose an appropriate chemical catalyst for this reaction system. The processes of preparation ofα-cyanobenzyl alcohol were studied in toluene by resin D301 and resin D201. The best initial concentration of acetone cyanohydrin with resin D301 as catalyst is 2 times the concentration of benzaldehyde, and the best initial concentration of acetone cyanohydrin with resin D201 as catalyst is 3 times. The reaction temperature is 40℃. The reaction is reversible reaction, and the internal and external diffusion can be ruled out. The reaction kinetics was studied in toluene with resin D201 as catalyst. The reaction rate equation isv=(k-1+k2)[R0](k4k3[D][C]-k-4k-3[P])/Σ1,where,Σ1=(k-3+k4)(k-1+k2)+(k-1+k2)(k3[D][C]+k-4[P])+(k-3+k4)(k1[A]+k-2[B][C]).The parameter values of the reaction rate equation were simulated by matlab program. The parameters were as follows: k1=1.210×10-5 L/mol/s, k-1=3.606×10-4s-1, k2=1. 803×10-4s-1, k-2=8.652×10-3L2/mol2/s, k3=6.438×10-3 L2/mol2/s, k-3=6.820×10-7 s-1,k4=1.790×10-6s-1,k(4)=8.638×10-5 L/mol/s. The relative error of the model was 7.87%. The model simulation curves were in good agreement with the experimental data.The lipase-catalyzed asymmetric transesterification ofα-cyanobenzyl alcohol in organic system was studied. The lipase Alcaligenes sp. (ZJU008) was screened to be used in this reaction. In solvent-free system, the optimal reaction temperature was 40℃. The external diffusion limitation could be reduced greatly by raising the rotation speed to 180r/min and the internal diffusion could be ignored. When the initial concentration ofα-cyanobenzyl alcohol was 100mmol/L and the reaction time was 240min, the yield of product was 49.32% and the e.e. value was 99%. The experimental results indicated that benzaldehyde and benzoic acid could greatly inhibit the enzyme activity. When the reaction was carried out in toluene system, the initial concentration of vinyl acetate must be three times the concentration ofα-cyanobenzyl alcohol. The internal and external diffusion can be ruled out. Using King-Altman method, a kinetic model of in solvent-free system without substrate and production inhibition was proposed based on ping-pong bi-bi mechanism. The reaction rate is:V=Vm[B]/KA+KBA[B]+KAB[B]+KQA[Q]+KBQA[B][Q].Using Matlab program tosimulate the processes and six parameters are obtained. The parameters were as follows: Vm=0.0060 mol/L/min, KA=0.4390 mol/L, KAB= 12.9552, KBA=0.3431, KQA=0.3059, KBQA=12.7496 L/mol. The simulated values can fit the experimental values quite well and the relative error of the model was 8.61%.The characteristics of the one-pot reaction were studied. The effects of solvent, temperature, internal and external diffusion, and concentration of substrate on this reaction were studied. When the reaction was carried out in solvent-free system with resin D301 as catalyst, 100mmol/L benzaldhyde,1500mmol/L acetone cyanohydrin, 5mg/mL resin and 10mg/mL enzyme, the yield of product was 92.52% and the e.e. value was 46.9%. The reason is thatα-cyanobenzyl alcohol and vinyl acetate can react with resin D301 as catalyst. Improving temperature can affect the e.e. value and concentration of enzyme can affect the yield of product. When the reaction was carried out in toluene system with resin D201 as catalyst, it was found that under the optimal conditions, with 100mmol/L benzaldhyde, 600mmol/L acetone cyanohydrin, 600mmol/L vinyl acetate, 5mg/mL resin, 10mg/mL enzyme, 40℃and rotation speed of 220r/min, the yield of product was 47.05% and the e.e. value was 93.63%. The reaction kinetics was studied, and the reaction rate equation is:v=k5k6k7k8k-9k10[G][PS][E0]/Σ1,where,Σ1=(k-5+k6)k 7k8k-9k-10[PS]+(k6+k8)k5k7k-9k-10[G][PS]+(k-5+k6)k-7k-8k-9k-10[Q]+(k-7+k8)k5k6k-9k-10[G]+(k-5+k6)k7k-8k-9k-10[PS][Q]+(k-5+k6)k7k8k9k-10[A][PS]+(k-5+k6)k7k8k-9k10[D][PS]The parameters of the equation were calculated through matlab program. The parameters were as follows: k5=1.758×10-6 L/mol/s, k-5=4.619×10-5s-1,k6= 5.358×10-6s-1, k7=4.942×10-6L/mol/s, k-7=3.315×10-6s-1, k8=7.232×10-6 L/mol/s, k-8=4.440×10-5s-1, k9=4.332×10-5 L/mol/s, k-9=1.438×10-5s-1, k10=8.574×10-6 L/mol/s, k-10=1.170×10-5s-1. The simulated values can fit the experimental values quite well and the relative error of the model was 3.89%. Though adding enzyme and vinyl acetate can improve the yield of product, which can reach 72.83%, and the e.e. value was 90.23%.In this paper, solvent extraction system is applied to separate the mixture ofα-cyanobenzyl alcohol andα-cyanobenzyl acetate for the first time. The basic consistence of the system is water and n-hexane with the phase ratio of 1.0. Operation parameters such as temperature, pH value in the aqueous phase and the concentration of the mixture and benzaldehyde were investigated to find the optimal conditions. When temperature was 30℃and pH value in the aqueous phase was 2.0, three-stage extraction was performed. The purity ofα-cyanobenzyl acetate in the organic phase was more than 99 % (mol) with the yield of 87.7 %. And the purity ofα-cyanobenzyl alcohol in the aqueous phase was 98.8 % (mol) with the yield of 92.6 %. This extraction system can separate the mixture ofα-cyanobenzyl alcohol andα-cyanobenzyl acetate efficiently.
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