Synthesis And Crystal Simulation Of 7-ADCA

7-aminodeacetoxycephalosporanic acid(7-ADCA)is one of the main starting materials for synthesizing semi-synthetic antibiotic cephalosporins such as cefadroxil,cephalexin and cephradine.7-ADCA mainly is synthesized by the steps of oxidation,ring expansion and cleavage using penicillin G potassium as raw material,so 7-ADCA is an important bridge for converting inexpensive penicillins into high-value cephalosporins.In industrial production,this process route of synthesizing 7-ADCA is long.The purity and crystal shape of each intermediate product will affect the subsequent synthesis reaction.In addition,the 7-ADCA product produced by this process has a small particle size,which is difficult to filter,and the quality of 7-ADCA is not stable and the crystal morphology of 7-ADCA is different.The difference in crystal morphology and the unstable quality will affect the purity and solubility of 7-ADCA,which will affect the cost of the synthesis process and the purity of the product in the downstream.This article systematically studied the synthesis process of 7-ADCA,and the crystallization mechanism and crystal appearance characteristics of 7-ADCA,in order to reduce the cost and pollution of the synthesis process and improve the quality of the product.First of all,the systhesis process of 7-ADCA was optimized.(1)Oxidation process:By using continuous feeding reaction crystallization method,the yield of penicillin sulfoxide obtained was 94.13%,and its purity was 98.8%.(2)The ring expansion:The yield and purity of the prepared cephalosporin G after decolorization and purification by activated charcoal were 84%and 98%,respectively.(3)Cleavage reaction:The yield and purity of the prepared 7-ADCA were 89.20%and 99.10%,respectively.The total yield of the entire process is 70.78%.Secondly,the effect of impurity ions and solvent on the morphology of 7-ADCA crystals was investigated.It was found that in the presence of H2O,H+ and OH-,7-ADCA crystals were octagonal.When the NH4+ ion is present,7-ADCA crystals were quadrangular.In the presence of SO42-ions,7-ADCA was hexagonal plate-like crystals.Through XRD and infrared analysis,the crystal polymorph of the three crystals were the same,but the crystal morphology was different.Finally,using the Forcite,Adsorption Locator and Morphology modules in the Materials Studio software predicted the crystal habits of 7-ADCA.The effects of solvent H2O,impurity ions NH4+ and SO42-on the morphology of 7-ADCA crystals were analyzed theoretically.The model used for crystal habit prediction was the modified AE model,and the simulation results are consistent with the experimental results.