Preparation and Structure Elucidation of Some Derivatives of Aryl Propionic Acid and Aryl Acetic Acid

Abstract

rylpropoionic acids, or Non-steroidal anti-inflammatory drugs (NSAIDs) are an important class of drugs used to suppress pain and inflammation in cases of rheumatoid arthritis and other inflammatory diseases. Recently, some non-steroidal anti-inflammatory drugs have emerged as a part of a new class of cancer chemotherapeutic and chemopreventive agents. Members of these class characterized by having several common chemical and biological features. Chapter one of this work covers a concise review of chemistry of NSAIDs including their review of main functional groups dealt with. Seventeen compounds derived from both sodium-2[2,6-dichlorophenyl- amino]-benzene acetate (I) and 2-(4-isobutylphenyl)propionic acid (XII) were prepared in this work. The synthetic designing of these compounds was worked out through the suitable retrosynthetic analysis and the use of the disconnection approach. One of the striking features in this work is the synthesis of 1-[2,6- dichlorophenyl]-oxindole (X). This compound is thought to be formed through intramolecular acyl substitution with subsequent ring formation. Multiple step synthesis was performed as a mean by which the sulphonamide and other acyl derivatives were prepared. Ring nitration was performed in standard nitration reaction with H2SO4/HNO3 followed by reduction with Sn/HCl and functionalization of the resulting amino group in compounds (I) and (XII). Esterification of both compounds (I) and (XII) resulting in formation of the corresponding alkyl and benzyl esters. The esterification step was performed either with alcohol and acid or with alkyl halide in the presence of K2CO3/acetone. The reactions performed was repeated eitherc with Sodium salts or with the free carboxylic acid form of starting materials. The mechanisms of the different reactions and the synthetic pathways in each case were heavily investigated and discussed in chapter three of this work. The reaction course were monitored by TLC technique, recrystallization and TLC were used for purification purposes. The structures of the prepared compounds were elucidated by spectroscopic means as IR, 1H- and 13C-NMR, MS, and UV data.