One‐Pot Knoevenagel–Michael–Cyclization Cascade Reaction for the Synthesis of Functionalized Novel 4H‐pyrans by Using ZnCl₂ as a Catalyst

Abstract

An expedient and cost‐effective protocol has been developed for the synthesis of novel 2‐methyl‐6‐(methylamino)‐5‐nitro‐4‐(4‐aryl)‐4H‐pyran‐3‐carboxylate derivatives. This domino, one‐pot, three‐component reaction was carried out between β‐ketoesters, aromatic aldehydes, and (E)‐N‐methyl‐1‐(methylthio)‐2‐nitroethenamine (NMSM) in the presence of 30 mol% anhydrous ZnCl2 under the neat condition at 120°C. The synthesized 4H‐pyran derivatives were characterized by spectroscopic techniques such as IR, 1H NMR, 13C NMR, CHNS, and HRMS. The molecular structure of compound methyl‐2‐methyl‐6‐(methylamino)‐5‐nitro‐4‐(4‐nitrophenyl)‐4H‐pyran‐3‐carboxylate 4a was confirmed by the single crystal X‐ray analysis. This solvent‐free protocol has several advantages such as shorter reaction time, an inexpensive catalyst, good yields, simple workup, and column‐free purification.

In water, Green and Efficient Multicomponent Synthesis of 4H-Pyran Derivatives catalyzed by LiOH·H 2 O under Ultrasound Irradiation

“…Khan et al synthesized pyran analogs using ZnCl 2 as a heterogeneous catalyst. The reaction, conducted in a solvent-free environment at 120°C, achieved a 70% yield within 30 minutes [73]. The condensation of benzaldehyde, malononitrile, and ethyl acetoacetate, catalyzed by silica nanoparticles xed with stannous chloride (SnCl2@nano SiO2), yielded between 82-96% under ethanol re ux for 25 minutes [74].…”

Recent Progress in the Multicomponent Synthesis of Pyran Derivatives by Sustainable Catalysts under Green Conditions

“…Khan et al [ 72 ] have synthesised pyran analogues ( 58 ) using ZnCl 2 as a heterogeneous catalyst. A single-pot multicomponent reaction system consisting of N -methyl thio nitroetheneamine (NMSM) ( 57 ), β ketoester ( 1 ) and aromatic aldehydes ( 56 ) in the presence of zinc chloride was used as a model reaction ( Scheme 19 ).…”

Nitroenediamines (EDAMs), and N-methyl-1-(methylthio)-2-nitroethenamine (NMSM) derivatives: scaffolds for heterocycle molecular diversity (update from 2012 to 2021)

“…This domino, one-pot reaction was performed for β-ketoesters 131, aromatic aldehydes 130, and ( E )- N -methyl-1-(methylthio)-2-nitroethenamine (NMSM) 4 under the neat condition ( Scheme 27 ). 32 …”