Preparation Of Functionalized Ionic Liquids And Application In Synthesis Of Cefditoren Pivoxil

Cefditoren pivoxil is one of important β-lactam type of cephalosporin drugs,usually used in the treatment of pneumonia,urinary tract infection,septicaemia,meningitis and other serious infections.The traditional method of synthesis of cefditoren pivoxil will use a large number of organic solvents and strong corrosion catalysts,which will damage the environment.And the technology of synthesis in functionalized ionic liquids not only can reduce or even avoid the use of organic solvents,also can improve product yield on the basis of which in traditional method,so as to solve the environmental pollution problems caused by the synthesis of cefditoren pivoxil in the traditional method.In this paper,the synthesis of functionalized ionic liquids will be researched and applied to the synthesis of cefditoren pivoxil in the three steps,mainly including Wittig r eaction,amidation reaction and esterification reaction.The specific work carry out in this thesis is summarized as follows:(1)Synthesizing [Bmim]Cl,[Bmim]PF6 in conventional method and introducing functional groups on their ions to synthesize various functionalized ionic liquids,such as [Bmim]OH,[EAmim]OH,[Bmim]OAc,[NH2-C2mim]PF6,[Hmim][HSO4],[Bmim][HSO4],[HSO3-Bmim][HSO4],[HN(Et)3][HSO4],[HSO3-BN(Et)3][HSO4],[HSO3-BN(Et)3][p-TSA].(2)The synthesis of 7-amino-3-[2-(4-methylthiazol-5-yl)vinyl]-3-cephem-4-carboxylicacid(7-ATCA)in ionic liquids were researched and be compared with traditional method.Also,the kind and amount of ionic liquids and catalyst,reaction temperature,reaction time on the reaction were discussed.The result was that when the amount of [Bmim]OH was 20 mL,DBU catalyst was 1mmol,the reaction temperature was 65℃,and the reaction time was 4 hours,the 7-ATCA yield could reach to 96%.(3)The synthesis of cefditoren in ionic liquid was researched and be compared with traditional method.Otherwise,the kind and amount of ionic liquids,the mole ratio of reactants,reaction temperature,reaction time on the reaction were discussed.The result is was when the amount of [Bmim]OH was 35 mL,the mole ratio of reactants(7-ATCA: AE active ester)was 1:1.3,the reaction temperature was 60℃,the reaction time was 2.5 hours,the cefditoren yield could reach to 93%.(4)The synthesis of cefditoren pivoxil in ionic liquids was researched and be compared with traditional method.In addition,the kind and amount of ionic liquid,the mole ratio of reactants,reaction temperature,reaction time on the reaction were discussed.The result is when amount of [HSO3-Bmim][HSO4] was 15 m L,the mole ratio of reactants(cefditoren: iodomethyl pivalate)was 1:1.4,the reaction temperature was 50℃,the reaction time was 3.5 hours,the cefditoren pivoxil yield could reach to 96%.