Cefaclor Synthesis

Cefaclor is a kind of cephalosporin antibiotics which is extensively used for anti-infection. It will devitalize transpeptidase, disturb the final step synthesis of the cell wall and prevent the cross bonding of mucopeptide. The main antimicrobial spectrum of cefaclor are staphylococcal bacteria (including coagulase masculine, Negative and the strains which can produce penicillinase), streptococcus (A group R — hemolytic streptococcus), diplococcus pneumonlae, Escherichia coil, bacillus proteus mirabilis, Klebsiella, hemophilus influenza (including mostly produce β— actam enzyme to endure ampicillin strain), neisseria gonorrhoeae (the strains which can and can not produce penicillinase), acne propionibacterium and bacteroides (not including Bacaeroides fragilis), Branhamell Catarrhalis, Citrobacter diversus, corynebacterium, Streptococcus and so on. This paper studies on the synthesis of cefaclor and probes into some factors during reaction.This paper studies on the synthetic route and corresponding conditions of process of cefaclor. First is the choice of the starting material, in this paper, penicillin G potassium is chosen as starting material for esterified protection instead of the traditional penicillin V potassium so that the production cost is greatly reduced. Then it is proved by experiment that it will dramatically improve the environment and decrease discharge of pollutants if the p-Nitrobenzyl Bromide which will seriously pollute the environment is replaced by diphenyl carbinol. During the study on Diphenylmethyl 6β-(2-phenylacetamide)penicillanate-1-Oxide, it is found that the reaction selectivity of present oxidant hydrogen peroxide is so low that the by-product penicillin sulfone ester which is difficult to isolate and purify will be produced. This affects the quality and yield of the product. In this paper, the homemade oxidant peroxyacetic acid is used. These not only improve the selectivity of sulphur atoms, but also make the yield and quality enhanced at least two percent.During the manufacturing of the critical intermediate cephalosporin nucleus --7-amino-3-chloro-cephalosporanic acid diphenylmethyl ester hydrochloride salt, first the feasibility of the one-pot synthetic route of open loop, closed loop and ozonization when chlorine is passed over is qualified by experiments. Then the critical factors that will influence this reaction are studied as follows: the mol ratio of triphenyl phosphite and Diphenylmethyl 3-hydroxy-7-phenylacetaminoceph-3-em-4-carboxylate-l(s)-oxide is four to one; the quantity of the stablizer should be at least more than two to one. The temperature of the system must be 25℃ when chlorine is passed over so that the hydrochloride can be precipitated to obtain cephalosporin nucleus of cefaclor--7-amino-3-chloro-cephalosporanic acid diphenylmethyl ester hydrochloride salt.As for the preparation of the intermediate 7-amino-3-chloro-cephalosporanic acid, inthis paper, trifuoroacetic acid and methylphenate are used to replace aluminium chloride and methylphenate that are used in the traditional process. In this way, the reaction conditions become milder and the yield and quality are ensured for the jelly will not produced during extraction.During the preparation of cefaclor, the critical influence factors are as follows: the reaction concentration of the starting material 7-amino-3-chloro-cephalosporanic acid should be 100mM; pH should be controlled around 6.5 so that the conversion can reach 95.6%; though the lower reaction temperature is, the higher conversion can reach, around 15℃ is the best point by evaluating economical efficieny. When the above factors are under control, the process continues with the condensation under catalysis of penicillin acylase, and at last cefaclor is obtained through extraction and crystallization. The assay can reach 99.5% (on an anhydrous base).