Study On Synthesis Of Cefquinome Sulfate

Cefquinome sulfate was developed by the German company Hoechst in the 1980 s.It was first listed in 1993 as the fourth-generation cephalosporin antibiotics special for animals.It is widespread concerned because of their good pharmacological properties and it will be a promising anti-infective drug.The development and mechanism of cephalosporin drugs was briefly described in this paper.The synthesis process of cefquinome sulfate was studied particularly for the purpose of reducing costs,improving yield,saving energy,protecting environment.In the first synthetic route,7-aminocephalosporanic acid（7-ACA）as materials were studied to synthesis 7-aminocefquinome（7-ACQ）hydroiodide by one-pot procedure: silicon alkylation reaction,iodine displacement reaction,nucleophilic substitution reaction,deprotection.7-ACQ hydroiodide was an important intermediate in the preparation of cefquinome sulfate.Instead of the traditional solvent Freon,dichloromethane was chosed as the solvent.Then cefquinome sulfate was synthesized by using 7-ACQ hydroiodide and MAEM,at the presence of triethylamine and sulfuric acid.Acetone and water was chosed as the solvent in this step.Each step of the synthetic process was studied and the better reaction conditions were obtained.The process was mild and environment-friendly and reduced the use of raw materials.Under the optimal conditions,the yield of cefquinome sulfate was 61.67% and the purity of the product was 98.67%.In the second synthetic route,7-ACA and MAEM as materials were studied to synthesis cefotaxima acid fistly.Ethanol was chosed as the cosolvent and tetrabutyl ammonium chloride was chosed as phase transfer catalyst.Then cefotaxima acid was reacted with 5,6,7,8-tetrahydroquinoline to synthesis cefquinome hydriodide by one-pot procedure: silicon alkylation reaction,iodine displacement reaction,nucleophilic substitution reaction,deprotection.Sulfuric acid as acidulant was added to form cefquinome sulfate at last.The process conditions were optimized.Under the optimal conditions,the yield of cefquinome sulfate was 55.88% and the purity of the product was 98.17%.Compared with the first synthetic route,dark-colored product was obtained and the yield and purity of the product were low.Finally,the product structure was confirmed by infrared spectrometry（IR）,nuclear magnetic resonance hydrogen spectrum analysis（1H-NMR）,nuclear magnetic resonance spectrometry(¹³C-NMR),mass spectrometry（MS）.