Synthesis Technics Research Of 7-Phenyl Acetamideyl-3-Vinyl Cephalkyl Acid P-Methoxy Benyl Ester

Cephalosporin which also named Cephalothin, is a type of broad-spectrumsemi-synthetical antibiotics. With the improvement of people's life level and people'srecognition for their own health, cephalosporin is getting more and more important inour life. The research and exploitation of cephalosporin medication is becoming moreimportant in medicine field. For its little toxicity, good antibacterial efficiency and thecharacteristic of having no or less cross hypersusceptibility, this sort of cephalosporinhas expansive application prospect.3-vinyl compound the critical intermediate for preparing Cefixime and Cefdinirmedication, therefore the study on its synthetical process is very important tosynthesize 3-vinyl cephalosporin. For being beneficial to develop study this kind ofcephalosporin medication, the research on 3-vinyl compound synthetical process isregarded as the paper's research object.According to the literatures in China and. aborad there are three methods ofcephalothin ring forming alkene bind: (1)by allenolic compound; (2)by 3—trifluorinmethyl sulphur acyl oxygen or 3—fluorin sulphur acyl oxygen compound; (3) byWitting Reaction.But the first above-mentioned two methods need special agents andspecial conditions. And productive rate is lower, literatures are less, and is notwell-known. But in Witting Reaction agents needed are easy to acquire, and itsreaction conditions is mild. The reports about it are universal, and the method is morewell-known. Therefore we choose Witting Reaction as method of alkylene. WittingReaction is the nucleophilic and addition reaction between Witting agent and carbonylof aldehyde or ketone, which can form alkene. The reactive conditions, which includeiodide, reactive solvent, the dose of formaldehyde and alkali, reactive time, andrefined solvent and etc, have effects on productive rate and quality for Wittingalkylene Reaction. Solvents, temperature and lithii compound have effects on the ratioof z-type and e-type in the reaction between ethene and 2-methyl thiazolyl ethylene in which there may be tridimensional isomers. The effects of above-mentionedconditions on alkylene reaction are studied to obtain the optimum reactive conditionsby orthogonal experiments having seven factors and three levels.GCLE is chosen as material to prepare 7-phenyl acetamideyl vinyl cephalkyl acidp-methoxy benyl eatsr in the experiment. The process is as follow: GCLE reacts withiodide in solvent, and produce 3-iodid, then reacts with PPh₃ to produce Witting agent,and reacts with HCHO to produce 7-phenyl acetamideyl vinyl cephalkyl acid p-methoxy benyl eatsr in alkaline conditions.In accord with the analysis of orthogonal table, the conclusions are obtained:choose NaI as iodide, K₂CO₃ as alkaline solution, the formaldehyde dose as 1:10, andacetone and CH₂Cl₂ as solvents. The time of two stages is one and four hoursrespectively, and the productive rate is high, and its crystal form is perfect, whichchoose methanol as solvent for after-treatment.So this is the optimum condition.