Preparation Of Chiral Amines By Dynamic Kinetic Resolution

In this paper, the carrier layered double hydroxide (LDH) was modified by different intercalatin ions, to prepare a group of Pd catalysts as the racemization catalyst. Racemization and dynamic kinetic resolution of (S)-1-(4-methoxyphenyl) ethylamine were investigated to study the effects of ion intercalation modified.After experiments we found these rules:Specific surface area of the catalyst will be reduced after ion intercalation modifying; the longer carbon chain length of the linear alkanoic acid ion intercalation, the smaller the specific surface area. When the ion contains unsaturation, the specific surface area is larger, and the specific surface area will increase along with the degree of unsaturation increases. But when it has a structure of benzene ring, the specific surface area will be smaller than the structure of the linear alkanoic acid. The ability of racemization of most of the catalysts promotes after intercalation modifing; among these catalysts, Pd/LDH-SA and Pd/LDH-DS are the best. When the intercalated ion is saturated alkane acid, the ability of the racemization of catalyst increases along with carbon chain of the ion increases. And when the ion contains unsaturation, the ability of racemization of catalyst is significantly weaker than the catalyst which is modified with saturated alkane acid; the greater the degree of the unsaturation, the worse the ability. When the ion contains other functional groups, the result of the reaction will be different; the ability of racemization of catalys will be weaker than ion with a structure of the linear when the ion contains a structure of benzene ring. Most of the catalysts with LDH as the carrier can be coupling with the Novozym435, and the effects of ion intercalation modified of racemization and dynamic kenetic resolution are the same.In addition, we investigated the effects of types of lipase, solvent, acyl donor substrate concentration, reaction temperature in the kinetic resolution reaction2-octylamine, an efficient kinetic resolution of2-octylamine was successfully built. And the best reaction reaction was confirmed:the reaction tube of2mL PE as the reaction vessel, toluene as the reaction solvent, the concentration of lipase Novozym435was20mg/mL, the substrate concentration was400mmol/L, the concentration of ethyl acetate2800mmol/L, the optimal reaction temperature is40℃, the reaction time was22h. Under these condition, a result was obtained with a conversion of50%, eep=100%. This kinetic resolution system can be also uned in the kinetic resolution of other applies fatty amines, and can achieve a higher conversion rate and a higher reaction product eep value. In addition, the use of previously prepared racemization catalyst for Dynamic Kinetic Resolution fatty amines, also achieved certain results.Finally, chiral drug was successfully synthesed using the chiral amines prepared by dynamic kinetic resolution.(R)-1-(1-naphthyl) ethylamine was successfully used in the synthesis of the second-generation calcimimetic Cinacalcet.