Synthetic and physicochemical studies in the aza-hetroaroamtics and amonoiminipropenes

Abstract

This thesis entitled, "Synthetic and Physico?chemical Studies in the Aza?heteroaromatics and Aminoiminiopropenes" consists of descriptions of methods leading to the formation of 2,6?disubstituted?7?nitroindazoles via a rearrangement of Schiff bases formed from 4?formyl?7?substituted benzofurazan N?oxides (benzofuroxans) with primary amines, the determination of the free energies of activation pertinent to dynamic tautomerisms in these systems (Part I) and a study of the field and resonance factors affecting the ¹³C chemical shifts in 1?dimethylamino?1?aryl?3?dimethyliminioprop? 1?ene perchlorates and certain related entities (Part II). i) An introductory section in Part I gives an overview of the work described. Following a brief historical review of the structure and synthesis of indazoles, the earlier exploitation of the anthranil–formylbenzofuroxan equilibrium for the synthesis of the indazoles is described. Work leading to the discovery that the iminoformylbenzofuroxans are isolable intermediates in the formation of indazoles in this method is then described. The iminoformylbenzofuroxans (as well as the formyl systems themselves) exhibit dynamic 1?oxide – 3?oxide tautomerism which is amenable to study by the DNMR technique. Following a brief description of particularities of this technique, results of its application to the cases of the benzofuroxans are given. An attempt is made to account for the downfield shift of C?5 and C?6 protons attendant on the tautomerism of the 1?oxide form to the 3?oxide form, instead of the expected upfield shift of C?5 proton and downfield shift of the C?6 proton, and the "exceptional" behaviour in this respect of 4?formyl?7?chlorobenzofuroxan is given in the next chapter. In the following chapter are described the results of attempts to displace the "nitro?activated" 7?chloro or 7?methoxy groups in 4?formyl?7?chloro or 7?methoxy benzofuroxans by an amino function, employing sec. amines. The products, which were well?crystallised solids, exhibited spectral properties (most importantly the absence of dynamic 1?oxide – 3?oxide tautomerism) which indicated that the products may not be the ones resulting from mere displacement of the 7?substituents by the amino function (7?aminated 4?formylbenzofuroxans) but could be 4?formylbenzofurazans with an N?oxide function at position 7 formed by internal transfer of oxygen in the initially formed aminobenzofuroxans. In further sections of this chapter, the attempts to obtain evidence to assign structures of this product unequivocally are detailed. Experimental details are given in a concluding section. ii) Certain steric situations can alter the correlations of ??parameters, pertinent even to meta and para?substituents, with certain measured properties. It was noticed that C chemical shifts of C? in 1?dimethylamino?3?dimethyliminio?1?arylprop? 1?ene perchlorates correlate with a ? set calculated by regression analysis. This contrasted with the behaviour of ??carbons in substituted styrene and acetophenones which show little variation in their chemical shifts with change in substitution. The known orthogonality of the aryl ring with respect to the propene plane in the aminoiminiopropene system with a 1?aryl substituent is used to explain this finding on the assumption that a compensatory effect, absent in these latter systems, operates in the styrenes and acetophenones. Other case studies, involving the variation of the free energy of activation pertinent to hindered amide rotation in substituted N,N?dimethylbenzamides and trans?cinnamamides with change in substitution and of the ??carbon chemical shifts in tris?para?substituted triarylcarbonium ions, are included in Part II. An Appendix records the interpretation of an incidental observation in connection with the formation of an indazole during an attempt to replace the 7?substituent by a dimethyl? amino function. A paper describing the results of the DNMR studies, included in Part I, has been published (J. Org. Chem., 45, 1653 (1980)). A second paper, containing the results included in Part II, has been communicated.