Study On The Synthetic Technologies Of Ultraviolet Absorbent CGL-479and The Side Chain Of Ceftazidime-activated Thioester

The1,3,5-triazine ultraviolet (UV) absorbent is a novel UV absorbent developed inrecent years. Due to its wide absorption spectra, high efficient, outstandingthermostability and well compatibility with polymer materials, its development hasbeen a hot spot for decades. However, the maximum absorption wavelengths of thesecommercially available1,3,5-triazine UV absorbents, such as UV-1577, UV-1164andtriazine-5, fall below300nm and have low absorption in UVA section (320~400nm).In order to develop a triazine UV absorbent with strong absorption in UVA section,Ciba-Geigy reported a novel UV absorbent named CGL-479, but there are fewliteratures about its synthetic technology. In the first part of this thesis, an applicableindustrial process was established. Taking Methyl2-bromopropionate, n-octanol,4-bromobiphenyl, cyanuric chloride and resorcinol as raw materials, using trans-esterification, Grignard reaction, Friedel-Crafts acylation reaction and etherification,CGL-479was obtained with a total yield of45.3%.The side chain of Ceftazidime-activated Thioester is the key intermediate of thethird and fourth generations of cephalosporin antibiotics, and its synthetic technologyhas been paid close attention for decades. However, the condensation reaction usingceftazidime acid to prepare the activated thioester suffers from several majordisadvantages from an industrial perspective, including high cost, environmentalpollution, and tedious work-up procedures. To obtain an effective and eco-friendlyprocess, its synthetic method was modified systematically in the second part of thisthesis. The condensation of ceftazidime acid with2,2’-dibenzothiazyl disulfide wasinvestigated, using trimethylphosphite as condensation agent and pyridine as catalyst,the side chain of Ceftazidime-activated Thioester was obtained with a yield of92.4%and purity of98.7%. The by-product2-mercaptobenzothiazole was also retrieved witha yield of75.2%and purity of99.5%. The reaction mechanism with different organicbases was also studied.