Study On The Synthesis Of Cyclooxygenase-2 Celecoxib Inhibitors

Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of arthritis and pain by inhibiting the activity of the cyclooxygenase (COX) which is the pivot enzyme in the synthesis of prostaglandins (PGs). COX exists in the form of two isomers (COX-1 and COX-2). Celecoxib, which shows few side effects, is one of the high selectively COX-2 inhibitors.In this thesis, celecoxib was synthesized through Claisen condensation and cyclization from the starting compounds p-methylacetophenone, ethyl trifluoroacetate and (4-sulfamoylphenyl) hydrazine hydrochloride. The total yield reached 45.3%.Firstly, p-methylacetophenone was obtained in the presence of alchlor as the catalyst, and the optimum condition was 4:1:2 in molar ratio for toluene, acetic anhydride and alchlor with yield of 86.2%.Then, a new method to synthesize ethyl trifluoroacetate was studied by using acidic resin D072 and absorbent resin as catalysts with 93.7% yield compared with the yield of 92.0% when concentrated sulfuric acid used in the reaction. The optimal dosage for the acidic resin, absorbent resin, trifluoroacetic acid and ethanol was 10g, 2.5g, 45.6g and 55.2g.Alkaline resin, as a new kind of catalyst, was used to synthesize 1-(4-methylphenyl)-4, 4, 4-trifluorobutane-1, 3-dione, and the yield was about 22%, which was much lower than the yield of 87.1%, when sodium methoxide used as the catalyst. However, this new method has great significance on the industry production and scientific research in the future.