Study On The Synthesiste Chnology Of Cefamandole

Cefamandole is a second-generation cephalosporin antibiotic, not only againstGram-positive bacteria have antibacterial activity against Gram-negative bacteria arealso strong. Mainly used for a variety of clinical infections caused by susceptiblestrains, such as respiratory infections, urinary tract infections, sepsis, and skin andsoft tissue, bone, joints and other infections. Development of cephalosporins latestart, the domestic market is a cephalosporin development period, increasingdemand. Aiming Cefamandole synthesis process technology, the synthetic route,influencing factors were analyzed synthesis process more systematic.In this paper,7-TMCA glycolic acid and benzene as raw material, throughseven condensation and subsequent crystallization process to obtain high qualityCefamandole through research, synthetic route design as:(1)7-ACA and A mercapto tetrazole (1-methyl-5-mercapto2,3,4-tetrazolium) by three condensation reaction of7-TMCA;(2) phenyl glyoxylic acid is not highly reactive carboxyl, hydroxy acid and thecarboxyl group of benzene using two microphones reaction active ester (hydroxyphenyl acetyl-1-imidazolyl), increase the activity of the condensation reaction ofacylation;(3)7-TMCA of seven amino and two protected silylated carboxyl group;(4) by silylation protection7-TMCA7-condensed reaction Cefamandole freeacid active ester by;(5) free Cefamandole acid and sodium salt formation ethylhexanoateCefamandole ester sodium.By influencing factors of synthetic routes variable single factor experiment, thefollowing conclusions.Using N, O-bis (trimethylsilyl) acetamide for the7-TMCA protected silylated7can effectively protect an amino group,two free carboxyl groups in the acidic,followed by silylation protected as esters,can effectively reduce the incidence of sideeffects.Benzene glycolic acid condensation directly with7-TMCA acylation reactionis very slow, after the activation of benzene glycolic acid carboxyl groups,according to the synthetic route for the synthesis of this article can be obtained moresatisfactory yield. When the condensation of the above acylation reaction time12hours,a highconversion rate of the target product, the weight yield of145%. Reaction rate overa period of time begins soon, with the reaction time, the reaction rate slowed down,when the reaction becomes more balanced, forward and reverse reaction rate tends tobe consistent with the target product is no longer increased. With the reactiontemperature increased, the reaction at the same time,0~20℃, the conversion rateof the target product increases progressively; when the temperature rises above20℃, little change in the yield of the desired product weight.7-TMCA glyoxylic acid with benzene in the synthesis of cefamandole optimalconditions for the:7-TMCA protected silylated using two microphones carboxyhydroxyl terephthalic acid carboxy-activated using boron trifluoride dimethylcarbonate7-TMCA synthesis catalyst, the condensation reaction of acylation ofabout10to12hours of time, the condensation temperature of the acylation reactionis20~25℃.