Study On Asymmerty Of High Value Chiral Alcohols

Asymmetric synthesis is a modern new synthetic technology.In recent years,by high selectivity,easy to operate and conducive to industrialization,its research has been the development of chiral drugs in the field of synthetic and continuous industrial applications.(S)-2-methyl-1,4-butanediol as an important pharmaceutical chemical intermediates and anti-counterfeiting discoloration of raw materials,with its increasingly wide range of applications,the demand for its diastereomers also increased year by year.The product is not industrialized production yet,generally taken with the outsourcing company custom synthesis,so the price of high withlong cycle and the production yield is low.Therefore,it is important to use the asymmetric synthesis technology of cheap raw materials to realize the industrial production of high value-added(S)-2-methyl-1,4-butanediol.In this paper,the asymmetric hydrogenation of(S)-2-methyl-1,4-butyldioate was carried out using L-BINAP catalytic system as the raw material,(S)-2-methyl-1,4-butanedioate was reduced to(S)-2-methyl-1,4-butanediol as a reducing agent.Follow-up for two-step reaction to carry out kilograms of production pilot experiment and evaluation.The effects of temperature,pressure,amount of catalyst,oxygen and water on asymmetric synthesis were studied.The temperature is high to accelerate the reaction rate,but when the temperature is higher than 0?,will affect the chiral catalyst diastereomeric selectivity,product e.e.value decreased;increase the hydrogen partial pressure and increase the catalyst ratio can shorten the reaction time.The proportion of less catalyst will lead to the reaction is difficult to occur;oxygen and water will destroy the chiral catalyst,so that asymmetric reaction product e.e.value decreased.After experimentally optimized,the preferred asymmetric synthesis conditions teamperature was-10?,the pressure of hydrogen was 0.1kg,the catalyst was 2%of the quality of the raw materials of itaconic acid,the dewatering operation was strictly dewate,the product yield was 100%,the e.e.value was 95.5%.Pilot lkg magnification experiment is preferably asymmetric synthesis conditions for the temperature-10?,hydrogen pressure 1Mpa,the catalyst for the quality of dimethyl itaconate 0.05%,Product yield 100%,e.e.value of 98.2%.(S)-2-methyl-1,4-butanedioate was reduced to(S)-2-methyl-1,4-dicarboxylic acid diacid diol.The results show that the yield of lithium aluminum hydride is high and the treatment is relatively easy.The reaction conditions of the small test and the pilot test are 1.05 times of lithium aluminum hydride(S)-2-methyl-1,4-butyldimethyl ester molar equivalent,and the mixture is quenched after stirring at 25 ? for 4h deal with.After purification of the product purity of 99%,the yield of 62.5%.The innovation of this topic is:1.(S)-2-methyl-1,4-butyldimethyl ester was synthesized by asymmetric synthesis of dimethyl itaconic acid,which was synthesized by the method described above(S)-2-methyl-1,4-butanediol.2.Improved post-treatment method,through the vacuum distillation of metal-free catalyst to obtain high-purity chiral alcohol products,chemical purity of 99%or more.At the same time can be achieved recovery of chiral catalyst in the precious metal composition,reduce production costs.3.Complete the 1kg per Lot of dimethyl itaconic acid asymmetric hydrogenation amplification experiments and get the desired results.For the industrialization of the product development to provide experimental support.