吡啶与7-苯乙酰氨基-3-氯甲基头孢烷烯酸对甲氧基苄酯碘代物亲核取代反应动力学

Kinetics on Nucleophilic Substitution Reaction of Pyridine with 7-Phenylacetamido-3-chloridecephem-4-carboxylic Acid p-Methoxybenzyl Ester Iodide

以7-苯乙酰氨基-3-氯甲基头孢烷烯酸对甲氧基苄酯(GCLE)和吡啶为原料合成头孢他啶中间体7-苯乙酰氨基-3-吡啶甲基头孢-4-羧酸对甲氧苄酯,用高效液相色谱仪监测了吡啶与GCLE碘取代物在二氯甲烷、丙酮、四氢呋喃、乙酸乙酯和DMF混合液中的亲核取代反应,反应动力学行为可用SN2机理解释。在一定的溶剂中不同温度的速率常数可用Arrhenius方程很好的关联,求得了指前因子,初步讨论了反应的溶剂效应,得出在不同溶剂中亲核取代反应活性顺序为:丙酮>四氢呋喃>乙酸乙酯-DMF混合液>二氯甲烷。

7-Phenylacetamido-3-pyridiniummethylcephem-4-carboxylic acid p-methoxybenzyl ester was prepared by the reaction of pyridine with 7-phenylacetamido-3-chloridecephem-4-carboxylic acid p-metho-xybenzyl ester iodide.The reaction process was inspected by HPLC in dichloromethane,acetone,tetrahydrofuran,the mixture of ethyl acetate and DMF.It was determined that the nucleophilic substitution reaction was a 2nd order reaction.In a given solvent the rate of the reaction perfectly obeyed Arrhenius′s equation within the experimental temperature of 25 ℃ and 35 ℃.The activation energy and the preexponential factor were obtained,and the solvent effects were discussed.The activity order of the nucleophilicity in different solvents is as follows：acetone〉tetrahydrofuran〉the mixture of ethyl acetate and DMF〉dichloromethane.