A Facile and Catalyst-Free Microwave-Promoted Multicomponent Reaction for the Synthesis of Functionalised 1,4-Dihydropyridines With Superb Selectivity and Yields

Abstract

We report a highly efficient green protocol for developing a novel library of 1,2,4-triazole-tagged 1,4-dihydropyridine analogs through the one-pot process from the four-component fusion of the 1H-1,2,4-triazol-3-amine with different chosen aldehydes, diethyl acetylenedicarboxylate, and active methylene compounds in a water medium under microwave irradiation and catalyst-free conditions. Excellent yields (94–97%) of the target products were achieved with high selectivity with a short reaction time (<12 min) at room temperature. The structures of the synthesized pyrimidine analogs were established by NMR and HRMS spectroscopic analysis. Simple workup, impressive yields, no column chromatography, green solvent, rapid reaction, and excellent functional group tolerance are the benefits of this protocol.

Transition‐Metal‐Free Synthesis of N‐Heterocyclic Compounds via Multi‐Component Reactions

“…An efficient MCR for the synthesis of functionalized 1,2,4‐triazole‐tagged 1,4‐dihydropyridine derivatives 507 was reported by Jonnalagadda et al (Scheme 96). [115] This method involves microwave irradiation (150 W) of a mixture of 1 H ‐1,2,4‐triazol‐3‐amine, aldehydes 1 , diethyl acetylenedicarboxylate 2 and active methylene compounds in a water for the synthesis of pyridine derivatives 507 with high selectivity and excellent yields (94–97 %). This green methodology furnishes the desired 1,4‐dihydropyridines 507 within a very short time (<12 min) and no column chromatography is required for purification of the product.…”

1,4-Dihydropyridine: synthetic advances, medicinal and insecticidal properties

“…Excellent yields (94–97%), functional group tolerance, and selectivity were all achieved throughout the reaction. 32 Similarly, the condensation of benzaldehyde 16a, ethyl acetoacetate 16b, and ammonia 16c in the presence of aqueous ethanol at room temperature was described as a visible light-mediated technique for the production of poly substituted 1,4-DHPs, 16. When compared to thermal procedures, this approach has the benefit of minimizing byproduct generation and having quicker reaction times ( Scheme 17 ).…”

Catalytic Approaches to Multicomponent Reactions: A Critical Review and Perspectives on the Roles of Catalysis

“…Isocyanide-based MCRs are sometimes performed in the absence of catalysts [ 62 ], but their catalytic versions proved to have many advantages. Some catalyst-free MCRs have been induced by alternative conditions, such as light-promoted reactions [ 63 ], microwave irradiation [ 64 ] and a few others [ 65 , 66 , 67 , 68 ], but catalysis effects rather than these conditions are of interest in the current article. Some MCRs have been labeled “catalyst-free”, but they have also been elegantly questioned [ 69 ], whereas other so-called “catalyst-free” MCRs could not be reproduced at all.…”