The dissertation is devoted to study of nucleophilic substitution of chlorine (bromine) atom in 2-halopyridinium salts with active methylenes, namely, acetonitrile derivatives, and further heterocyclization of products. The general principles of the reactions were found; the influence of substituent's nature on the yields of target products and general directions of studies reactions were established.
The optimal conditions for the synthesis of 2-halo-N-ethoxycarbonylmethyl-pyridinium halides without solvent and the first synthesis of 2-halo-N-methoxycarbonylmethyl- and 2-halo-N-allylpyridinium halides were proposed.
A mixture of pyridine-2-thiones and 2-amino-1-cyanoindolizines was obtained by condensation of N-[(alkoxycarbonyl)methyl]- or N-[(aroyl)methyl]-2-halo-pyridinium halides in the presence of 2 equivalents of triethylamine. Furthermore, reacting cyanoacetamide with N-[(alkoxycarbonyl)methyl]-2-halopyridinium salts afforded a mixture of 2-amino-1-carbamoylindolizine-3-carboxylates and a novel heterocyclic system, 2,4-dioxo-2,3,4,5-tetrahydropyrido[1,2-d][1,4]diazepine-1-carbonitrile.
An efficient protocol for the synthesis of highly functionalized 2-aminoindolizines and pyrido[3,2-a]indolizines has been achieved via the reaction of N-RC(O)CH2-2-halopyridinium halides with 2-amino-1,1,3-tricyanopropene. The reaction of N-allyl-2-halopyridinium halides with 2-amino-1,1,3-tricyanopropene in the presence of Et3N gives 3-[1-allylpyridin-2(1H)-ylidene]-2-aminoprop-l-ene-1,1,3-tricarbonitrile, which could be cyclized to give [2-amino-(2-amino-3-vinylindolizin-1-yl)methylene]malononitrile upon treatment with KOH-DMF.
The two-component condensation of 2-halo-N-ethoxycarbonylmethyl-pyridinium halides and aryl- or hetarylmethylidenemalononitriles gave ethyl 2-[2-(dicyanomethylidene)pyridin-1(2H)-yl]-3-arylacrylates. In all cases, 2-amino-1-cyano-3-ethoxycarbonylindolizine was formed as a by-product in addition to the major products ethyl 2-[2-(dicyanomethylidene)pyridin-1(2H)-yl]-3-arylacrylates. 2-Halo-N-allylpyridinium salts react with 2-benzylidenemalononitrile in the presence of two equivalents of triethylamine to give product of nucleophilic substitution, namely, 2-(1-allylpyridin-2(1H)-ylidene)malononitrile.
Keywords: 2-bromo(chloro)pyridinium salts, CH-acid, activated alkenes, 2-aminoindolizine, 2,4-dioxo-2,3,4,5-tetrahydropyrido[1,2-d][1,4]diazepine-1-carbo-nitrile, 2,4-diamino-3-cyanopyrido[3,2-a]indolizine-10-carboxylate, ethyl 2-(2-(dicyanomethylene)-pyridin-1(2H)-yl)acrylates.
