Study On The Synthesis Of N-hydroxysuccinimide

N-hydroxy succinimide is an important lactam compounds,because of the lively structure of hydroxy-containing with nitrogen,N-hydroxy succinimide can synthesis with antigen,enzyme,amino,carboxyl and glycosyl of nucleic acid,combination without affecting their activity,so it can be used as precursors in synthetic process of peptides,antibiotics, amino acids and protein,it can be also used in the affinity chromatography,diagnostic tumor imaging and treatment.This article introduced the physical-chemical properties,the domestic and foreign research status as well as the related use of N-hydroxy-succinimide,based on the domestic and foreign literature and the predecessor study,this paper chose the industrial products of hydroxylamine hydrochloride and succinic anhydride for raw materials,NaOH as catalyst,synthesis of N-hydroxy succinimide.This synthesis method is a two-stage process route.The purpose of this study worked in the following areas:(1) synthesis of N-hydroxy succinimideFirst,we designed the synthetic route of N-hydroxy succinimide,then studying the various factors(such as the ratio of raw materials,reaction temperature,reaction time, reaction pressure,etc.) on the product yield,at last,through single-factor experiment and orthogonal experiment,we determined the optimum route of the vacuum process.The results as follows:the molar ratio of succinic andride and hydroxylamine hydrochloride is 1.2:1,the reaction temperature is 140℃and the reaction time is 60 min.Under these conditions,the yield of N-hydroxy-succinimide is up to 95%.(2) Separation of N-hydroxy succinimideIt was determine the solubility of N-hydroxy succinimide in different organic solvents, selected the extraction solvent,and then optimized the separation process conditions,the results show that:ethyl acetate is the best separation solvents;the amount of extraction solvent is 200ml;extraction methods is the batch extraction;extraction time is 60min,under these conditions,the yield is 96.28%.(3) N-hydroxy succinimide refinedThe refining process conditions Of N-hydroxy succinimide were discussed,the best conditions as follows:the amount of concentrated liquid is 75～80ml;crystallization temperature is 0℃;the crystallization time is 90 min;crystal frequency is 2 times; recrystallization solvent dosage is 105～110ml,the secondary crystallization yield of N-hydroxy succinimide is 93.46%,the melting point is 95-98℃.(4) recycling of solvent Effect of recycling solvents on the yield was discussed,the experimental results show that:the recovery rate of ethyl acetate is 56%,reusing of recycling solvents had no effect to the yield and purity of product.Because of reuse of recycling solvents,the entire process is very economic,and the economic efficiency is increasing.