Development Of Synthetic Process Of Mono-p-nitrobenzyl Malonate

Mono-p-nitrobenzyl malonate and its derivatives are important basic raw materials for the production of antibiotics.This article reviewed the definition and classification of antibiotics,the synthetic routes of meropenem and biapenem,and the synthetic methods of monoesterification of dicarboxylic acid were reviewed,The route was explored for the synthesis and process development of mono-p-nitrobenzyl malonate.Through the comparative analysis of various monoesterification experiments,Various influencing conditions in the experiment were improved.Finally,an industrial production route suitable for mono-p-nitrobenzyl malonate was determined.This method improves the utilization rate of raw materials and reduces the reaction cost.This article has designed three synthetic routes,and by exploring and comparing each route,finally determine the process route to obtain mono-p-nitrobenzyl malonate by esterification of p-nitrobenzyl alcohol and malonic acid,and then purify to obtain high purity products that meet the quality requirements.Meanwhile the by-product bis（4-nitrophenylmethyl）malonate was hydrolyzed to p-nitrobenzyl alcohol,which realized the recycling of the by-product.In this process,the effects of various conditions on the reaction were investigated.The optimal conditions were determined as follows : toluene as solvent,methanesulfonic acid as catalyst,0.05 eq（based on p-nitrobenzyl alcohol）dosage,110 ℃ reaction temperature,5 h reaction time,500 r / min stirring speed and 1 : 1.5 molar ratio of alcohol to acid.At the same time,the purification of products,the application of solvents and the comprehensive treatment of three wastes were studied to determine the optimal process route.In the study of comprehensive utilization of by-products,the recycling of p-nitrobenzyl alcohol was realized by hydrolysis of bis（4-nitromethyl）malonate.The hydrolysis reaction was explored,and the optimal reaction conditions were finally determined as follows : Na OH as the catalyst,solvent as pure water,reaction temperature 80 ℃,reaction time 5 h,reaction system p H≈11,and stirring rate 500 r / min.