Kinetic study of the indomethacin synthesis and thermal decomposition reactions

The kinetics of indomethacin synthesis (achieved through a new method) was studied at 80 degreesC. The reaction proceeds in four steps. In the first s tep; by the condensation of levulinic acid with p-chlorobenzoyl-p-methoxy-p henyl-hydrazine in homogeneous acidic catalysis an intermediate is formed. In the second step, by the isomerisation of this intermediate a hydrate com pound is formed. In the third step, the isomerisation is followed by the o- benzydinic transposition of the reaction product mentioned above. In the fo urth step, indomethacin is formed through a cyclization reaction. The rate constant of the indomethacin synthesis reaction was determined assuming tha t the cyclization reaction constitutes the rate-determining step. Spectroph otometric methods were used both in order to investigate the kinetics of th e synthesis reaction and to verify the proposed mechanism. Then, a thermogr avimetric study was performed on the purpose of finding out the temperature range in which indomethacin is stable. From the thermogravimetric curve ki netic parameters have been derived, using different calculation techniques. (C) 2000 Elsevier Science B.V. All rights reserved.