Synthetic investigations involving chiral drug intermediates and syntheses of heterocycles guided by mass spectral fragmentations

Abstract

In the early twentieth century, the relevance of chirality to the pharmaceutical industry was established by the fact that one enantiomer of hyoscyamine possessed greater pharmacological activity than the other. The chiral pool of readily available, relatively inexpensive chiral compounds has been expanding at a rapid rate as more and more products are produced in large quantities at economical prices. The present work has mainly focused on developing some of the chiral drugs/intermediates using techniques like asymmetric induction through Grignard reaction, hydrogenation and chemical manipulation of chiral molecules. The present thesis comprises of four chapters. First chapter deals with the introduction and scope of the work, second chapter describes experimental procedures for the compounds synthesized and the third chapter focuses on results and discussion. The summary and the conclusion derived from the present investigation are provided in the fourth chapter. The present study makes use of mass spectral fragmentations of 2 -substituted phthalanilic acids and 2-nitrophenyl phenyl disulphide to synthesise 1,2-benzoylenebenzimidazole, dibenzo[b,f]-1,4- (5H,12H)-diazocin-6,11-dione, 2-phenylbenzoxazole, 2-phenylbenzothiazole and thianthrene using thermolytic procedures. The mechanisms for the formation of these heterocyclic compounds were provided. The present work thus demonstrates efficient processes for the syntheses of several chiral drug intermediates with high optical purity and also the pyrolytic methods for the synthesis of tri-and tetracyclic heterocycles. The structures of all the compounds have been established with the help of IR,1H NMR,13C NMR and mass spectra while their optical purities by using chiral column in HPLC. newline newline newline