Study On Synthesis Of Caffeine

Caffeine,as a kind of alkaloids,is mainly found in the tea,coffee,cocoa and korah in nature.It was first extracted in the green coffee beans by German chemist Friedrich Ferdinand Runge in 1820 and then totally synthesized by Fischer and Ach in 1895.As a central nervous system stimulant,caffeine is not only used as the heart and respiratory stimulants in clinic,also can be used as an antipyretic analgesic adjuvant and food additive.The most widely used synthetic route of caffeine starts from cyanoacetic acid and dimethyl urea by using acetic anhydride as condensing agent to give 1,3-dimethyl nitrile acetyl urea,which was cyclized under the action of sodium hydroxide to afford1,3-dimethyl-4-imine urea oxazine,then theophylline was obtained through the nitrosation,reduction,formylation and cyclization,finally,caffeine was produced after methylation by dimethyl sulfate.In this paper,caffeine synthetic technology of Xinnuowei Pharmaceutical Group Limited(CSPC)is studied.The technologies of reduction,formylation,cyclization and acidification were studied in detail based on the reported literature.After a large number of experiments,an optimal manufacturing process with less impurity and higher yield was determined and confirmed by scale-up production.At the same time,the recrystallization of theophylline was researched to give satisfactory product without yellow-green impurity and the amount of water consumption is less than one-tenth of the original water amount.This method was also confirmed by the scale up manufacture test and applied in the industrial production.