Study On The Methylation Of Pyrazolone

Methylation is commonly used in organic synthesis fields. Many important chemicals and pharmaceutical intermediates are synthesized by methylation, like dimethyl sulfoxide, caffeine, codeine, vanillin, aminopyrine, trimethoprim and pesticides acephate, etc.. In the synthesis processof analgin, intermediates antipyrine is obtained by the the methylation of pyrazolone, and4-amide antipyrine areobtained by amino-protecting and methylation of aminopyrine. With more and more people pay attention to the high toxicity of dimethyl sulfate, trying to reduce the amount of dimethyl sulfate is of great significance to personal safety and environmental protection.The work are carried out a series of experiments of N-methylation. The reaction process of dimethyl sulfate for the methylating agent and pyrazolone is very mature, this work mainly discussed the effect of various factors on the reaction, such as, the quantity of reactants, reaction temperature and time. Under the best conditions, the reaction was carried out. Detecting the changes in concentration of the reactants, we obtain a reaction kinetic curve, and the optimum reaction time based on the needs of industrial production.We also studied the using of dimethyl carbonate and trimethyl phosphate as the methylation agents and explored the feasibility of the reaction. Under the experimental conditions, the yield of the N-methylated product (antipyrine) was low with dimethyl carbonate as the methylation agents, which can not meet therequirements of standard industrial production, so more studies are required; Themethylation with trirnethylphosphate got high yield, but the selection of methylating agents need to consider the toxicity of agents and the effect on the reaction.The first methyl of dimethyl sulfate reacted at a quite high rate. In dustrial production, First methyl of dimethyl sulfate only was used sufficiently in N-methylation reaction. But in the experiment, we found the second methy of dimethyl sulfate can be involved in the reaction well,(monomethyl sulfate is also involved in the methylation reaction).