Solvent effect and catalysis in the synthesis of thiosemicarbazone derivatives from ketones and 4-phenylthiosemicarbazide

Abstract

In this paper, we performed a series of experiments aiming at establishing the solvent effects in the condensation of 4-phenylthiosemicarbazide with 4-nitroacetophenone to form the expected thiosemicarbazone derivative, reaction  which  was chosen  as pilot reaction, having in mind to set up optimal reaction conditions for the future elaboration of a compound library of thiosemicarbazone derivatives. Methanol was found to be a suitable solvent for this purpose. As a general rule, acid catalysis was found to perform better than base catalysis. General acid-base catalysis performed also in a quite satisfactory manner and in this connection, among the catalytic systems, anilinium chloride performed optimally allowing the reaction to go to completion at room temperature in excellent yield within 24 h at room temperature.  A series of six bench mark molecules of increasing steric effect were synthesized in fair to good yields using this method.   Key words: Thiosemicarbazone, thiosemicarbazide, solvent effect, acid-base catalysis, alpha-effect, nucleophilic catalysis, anilinium catalysis.