The Synthesis and Properties of Some Aminoindolizines

Abstract

The chemical properties of indolizines, the synthesis of potential precursors of aminoindolizines, and the synthesis and properties of known aminoindolizines, are reviewed. The work described in this thesis concerned the preparation of further examples of 3-aminoindolizines, and their precursors, and a study of some of their physical and chemical properties. The synthesis of several new 3-azoindolizinesand 3-nitrosoindolizines is described, and the successful nitration at the 3- position of indolizine and 2-methylindolizine with acetylnitrate, is reported. The orientation of nitration products of indolizines is discussed and a tentative conclusion has been drawn to rationalise the changes in orientation which occur. Rapid reduction procedures have given 3-aminoindolizines, and their physical properties and stability is described. The products of acetylation of the 3-aminoindolizines are reported, and the anomolous n.m.r. spectra of the 3-acetamidoindolizines is discussed. Hydrolytic ring-cleavage of 3-amino and 3-acetamidoindolizines, on treatment with mineral acid, is reported, and a possible mechanism is outlined for this reaction. The products of hydrolysis are shown to be 3-(2-pyridyl)propionic acids. Ring-cleavage of 3-aminoindolizines under neutral, mild conditions by oxidative reactions, is described, and it is shown that progenitor 3-nitrosoindolizines are capable of oxidising the 3-aminoindolizines. The products of this ring-cleavage are shown to be cis 3-(2-pyridyl)acrylonitriles. 2-Phenyl-3-(2-pyridyl) acrylonitrile has been prepared by the deoxygenation of 3-nitroso-2-phenylindolizine. The possible nature of an intermediate nitrene is discussed with reference to oxidation of other aromatic amines. The 3-nitrosoindolizines are shown to undergo several autoxidation reactions. The mass spectra of several 3-nitro, 3-nitroso, 3-amino and 3-acetamidoindolizines, are discussed, together with those of the 3-(2-pyridyl)acrylonitriles derived from these compounds. Possible fragmentation patterns are suggested.