[bmim]OH promoted hydroalkynylation of nitrile and intramolecular hydroamination of the carbon–carbon multiple bond: an efficient and eco-compatible strategy for the synthesis of indolizinones

Abstract

An efficient and novel hydroalkynylation of 2-cyanopyridine with arylacetylene and a subsequent intramolecular hydroamination promoted by a basic ionic-liquid, [bmim]OH, under microwave activation in the absence of an organic solvent and an inorganic base, yielding biodynamic indolizinones has been developed. The protocol involves [bmim]OH mediated in situ generation and addition of a nucleophilic alkynide from the aryl substituted terminal on a carbon alkyne of a polar nitrile group of 2-cyanopyridine. This results in the formation of a 2-pyridylphenylethynyl methimine intermediate which, on subsquent intramolecular nucleophilic addition of a pyridyl nitrogen on the carbon-carbon triple bond of the imine intermediate, heterocyclized into indolizinone with high atom economy. The reaction proceeded smoothly and quantitatively at an ambient temperature. The task specific [bmim]OH was recovered and reused three times without any appreciable decrease in its activity and product yield.

Synthesis of Novel Benzo[6,7][1,4]oxazepino[4,5-a]quinazolinone Derivatives via Transition-Metal-Free Intramolecular Hydroamination

“…Intramolecular and intermolecular hydroamination reactions constitute a versatile and atom economic synthetic process for the direct formation of a C-N bond leading to nitrogen-containing heterocycles. [1][2][3] Various structures such as complex sulfonamide scaffolds, 4 indolizinones, 5 indolo [1,2-c]quinazolines, 6 azomethine imines, 7 tetrahydroisoquinoline alkaloids, 8 N-heterocyclic carbenes, 9 and pyrazoles 10 have been successfully prepared by this approach. The range of reports concerning hydroamination reactions [11][12][13][14] confirm hydroamination as a strategy for the preparation of N-heterocyclic compounds.…”