Recovery Of Cephalexin From Crystalline Mother Liquor

Cephalexin(CEX)is one of a cephalosporin that widely used in clinical,and can be prepared chemically or enzymatically in industry.The CEX in the reaction solution can be extracted by isoelectric point crystallization(pH=4.72).After crystallization,about 12～15 g·L-1 of CEX products remains in the crystalline mother liquor,accounting for about 10%of the total amount.The residual CEX in the crystalline mother liquor must be recovered,or it will not only cause economic losses,but also serious environmental pollution.The CEX in the crystalline mother liquor is generally recovered by the complexation.Complexation has the advantages of high selectivity and high complexation-efficiency,so it has great advantage in recovering low concentrations of CEX.In current industry,the complexing agent is 2-naphthol,and the decomplexing agent is dichloromethane.The complexation rate of CEX is about 92%.Dichloromethane is easy to volatilize,and it produces large amounts of VOC,resulting in serious environmental pollution.In this paper,a recovery process of CEX in the crystalline mother liquor was systematically studied,and a new recovery process was established.That is using 1-naphthol as complexing agent and trioctylamine(TOA)as decomplexing agent.The complexation rate of CEX increased by five per cent,and the substitution of the decomplexing agent dichloromethane was achieved.The VOC pollution caused by volatilization of organic solvent was eliminated from the source of the process,and the amount of the decomplexing agent was reduced by 92%.Meanwhile,the circulation utilization of the decomplexing agent was realized.The main works are as follows:(1)The benzene and naphthalene compounds were used as complexing agents,and the effects of complexing agent type and its dosage,pH,temperature,concentrations of residual raw materials such as 7-amino-3-desacetoxicephalosporanic acid(7-ADCA),Phenylglycine methyl ester hydrochloride(PGME)and the main by-product phenylglycine(PG)on the complexation process were investigated.Results show the complexing agent type,its dosage and pH were the key factors affecting the complexation process.Using 1-naphthol as complexing agent,the optimal parameters were as follows:1-naphthol dosage 4.4 g·L-1,pH 4.72,temperature 20℃.Under the optimal conditions,the complexation rate of CEX reached 97.41%,a five per cent increased than that in industrial process.(2)The high-boiling amines were used as decomplexing agents,and the effects of decomplexing agent type,material ratio,pH and temperature on the decomplexation process of CEX were investigated.Results show the decomplexing agent type,material ratio and pH were the key factors affecting the decomplexation process.Trioctylamine(TOA)was determined as the best decomplexing agent.The decomplexation rate of CEX reached 99.43%under the optimal conditions of TOA/water=0.2,water/clathrates 4.8 ml·g-1,pH=1.2 and temperature of 20℃,compared with the arrent production process,the amount of decomplexing agent was reduced by 92%.The VOC pollution was eliminated from the source of process by using TOA as decomplexing agent.(3)Recovery of complexing agent and TOA were achieved by using NaOH solution as extracting agent,the recovery rate reached 98.09%and 90.6%,respectively.A new chemical recovery method and content detection standard of the recycled decomplexing agent TOA were established.After five cycles of TOA,its decomplexation capacity for CEX was still more than 98%.Using FT-IR spectroscopy analysis,the formation of hydrogen bond was confirmed to be the driving force for the decomplexation process.(4)In the crystalline mother liquor obtained in the industrial production,the complexation-decomplexation continuous operation of CEX were performed,the complexation rate and decomplexation rate of CEX reached 97.3%and 99.3%,respectively.The content of related substances in the recovered CEX products complies with the requirements of the Chinese Pharmacopoeia.The new process has the basis for industrial amplification.