Efficient Synthesis of Chromeno[4,3,2‐de] [1,6]naphthyridine Derivatives via Pseudo Four‐Component Reaction

Abstract

A novel approach to the synthesis of substituted 5-amino-4cyanochromeno[4,3,2-de][1,6]naphthyridine-1-carboxylates from a wide range of substituted 2-hydroxybenzaldehydes with alkyl 3-oxo-3-substituted propanoates and malononitrile was investigated via propionic acid-promoted cascade Knoevenagel condensation/Michael addition/intramolecularly nucleophilic addition accompanied by oxidative aromatization. This procedure provided a highly efficient and facile route to functionalized chromenonaphthyridines from readily available substrates under mild reaction conditions.

Synthesis of novel chromeno[1,6]naphthyridine derivatives in PEG-400 via catalyst-free, one-pot, and multicomponent reactions

“…13 In 2021, Wang et al reported a novel approach for the synthesis of chromeno[4,3,2- de ][1,6]naphthyridine derivatives from a wide range of 2-hydroxybenzaldehydes with alkyl 3-oxo-3-substituted propanoates and malononitrile via a propionic-acid-promoted cascade Knoevenagel condensation/Michael addition/intramolecularly nucleophilic addition accompanied by oxidative aromatization. 14…”

“…13 In 2021, Wang et al reported a novel approach for the synthesis of chromeno [4,3,2-de][1,6]naphthyridine derivatives from a wide range of 2-hydroxybenzaldehydes with alkyl 3-oxo-3-substituted propanoates and malononitrile via a propionic-acid-promoted cascade Knoevenagel condensation/Michael addition/intramolecularly nucleophilic addition accompanied by oxidative aromatization. 14 Recently, Elinson et al reported the synthesis of benzo[b] chromeno [4,3,2-de][1,6]naphthyridines via an intermolecular oxidative cyclization of 5-(2-hydroxy-6-oxocyclohexyl)-5H-chromeno [2,3-b] pyridines in formic acid. 15 In this line of research and in continuation of our research on the synthesis of novel heterocycles, 16 herein, we report an efficient method for the synthesis of chromeno [1,6]naphthyridine derivatives via a one-pot, three-component condensation reaction between salicylaldehyde derivatives, malononitrile dimer, and active methylene group compounds (5-amino-3-(cyanomethyl)-1H-pyrazole-4carbonitrile/5-amino-3-(cyanomethyl)isoxazole-4 carbonitrile/2-(cyanomethyl) pyrazolo [1,5-a]pyrimidine-3-carbonitrile derivatives/ malononitrile dimer/alkyl malonates) in polyethylene glycol-400 (PEG-400) at 80 1C (Scheme 1).…”