Optimization of technological conditions for one-pot synthesis of (S)-alpha-cyano-3-phenoxybenzyl acetate in organic media.
Optically active form of alpha-cyano-3-phenoxybenzyl (CPB) alcohol, building block of pyrethroid insecticides, was synthesized as its acetate by the combination of anion-exchange resin (D301)-catalyzed transcyanation between m-phenoxybenzaldehyde (m-PBA) and acetone cyanohydrin (AC), and lipase (from Alcaligenes sp.)-catalyzed enantioselective transesterification of the resulting cyanohydrin with vinyl acetate. Through optimizing technological conditions, the catalyzing efficiency was improved considerably compared to methods previously reported. Concentrations of CPB acetate were determined by gas chromatograph. The enantio excess (e.e.) values of CPB acetate were measured by NMR (nuclear magnetic resonance) method. Effects of solvents and temperatures on this reaction were studied. Cyclohexane was shown to be the best solvent among the three tested solvents. 55 degrees C was the optimal temperature for higher degree of conversion. External diffusion limitation was excluded by raising the rotational speed to 220 r/min. However, internal diffusion could not be ignored, since the catalyst (lipase) was an immobilized enzyme and its particle dimension was not made small enough. The reaction rate was substantially accelerated when the reactant (m-PBA) concentration was as high as 249 mmol/L, but decreased when the initial concentration of m-PBA reached to 277 mmol/L. It was also found that the catalyzing capability of recovered lipase was high enough to use several batches. Study of the mole ratio of AC to m-PBA showed that 2:1 was the best choice. The strategy of adding base catalyst D301 was found to be an important factor in improving the degree of conversion of the reaction from 20% to 80%. The highest degree of conversion of the reaction has reached up to 80%.
Zhang
Ting-Zhou
TZ
School of Material & Chemical Engineering, Zhejiang University, Hangzhou 310027, China. zhangtz@hzcnc.com
Yang
Li-Rong
LR
Zhu
Zi-Qiang
ZQ
D000421:Alcaligenes / Q000201:enzymology*; D001547:Benzaldehydes / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D008049:Lipase / Q000737:chemistry*; D009570:Nitriles / Q000737:chemistry*; D009930:Organic Chemicals / Q000737:chemistry; D010647:Phenyl Ethers / Q000138:chemical synthesis*; D013678:Technology, Pharmaceutical / Q000379:methods*
D001547:Benzaldehydes; D009570:Nitriles; D009930:Organic Chemicals; D010647:Phenyl Ethers; C117373:cyano-3-phenoxybenzyl acetate; C010833:acetone cyanohydrin; D008049:Lipase