Kinetic study of the indomethacin synthesis and thermal decomposition reactions

The kinetics of indomethacin synthesis (achieved through a new method) was studied at 80 degrees C. The reaction proceeds in four steps. In the first step, by the condensation of levulinic acid with p-chlorobenzoyl-p-methoxy-phenyl-hydrazine in homogeneous acidic catalysis an intermediate is formed. In the second step, by the isomerisation of this intermediate a hydrazo compound is formed. In the third step, the isomerisation is followed by the o-benzydinic transposition of the reaction product mentioned above. In the fourth step, indomethacin is formed through a cyclization reaction. The rate constant of the indomethacin synthesis reaction was determined assuming that the cyclization reaction constitutes the rate-determining step. Spectrophotometric methods were used both in order to investigate the kinetics of the synthesis reaction and to verify the proposed mechanism. Then, a thermogravimetric study was performed on the purpose of finding out the temperature range in which indomethacin is stable. From the thermogravimetric curve kinetic parameters have been derived, using different calculation techniques.