Synthesis of new substituted pyridines via Vilsmeier-Haack reagent

Abstract

New substituted pyridines were synthesized by the reaction of spiroimidazolidinones with the Vilsmeier-Haack reagent (PBr3/DMF) with satisfactory yields. The reaction proceeds as an electrophilic trigger process according to the push-pull mechanism due to the anomeric effect of two nitrogen atoms with an increase in the primary heterocycle. An explanation is proposed for the different chemical behavior of 5',6',7',8'-tetrahydro-1'H-spiro[cyclohexane-1,2'-quinazolin]-4'(3'H)-one and spiroimidazolidinones under Vilsmeier-Haack reaction conditions. The likely reason is the hybridization of the amine (enamine) nitrogen atom in the structure of heterocycles. The reaction of spiroimidazolidinones with the Vilsmeier-Haack reagent results in formylation of the ammine nitrogen atom with subsequent reaction steps; and in the case of 5',6',7',8'-tetrahydro-1'H-spiro[cyclohexane-1,2'-quinazolin]-4'(3'H)-one, the reaction results in formylation of carbon atom followed by heterocycle opening and its intramolecular cyclization. The synthesized new pyridine derivatives, due to the presence of several reaction centers in them, are of interest not only as potential pharmacologically active compounds, but also as low-molecular building blocks for organic synthesis.