InCl₃‐Assisted Eco‐Friendly Approach for N‐Fused 1,4‐Dihydropyridine Scaffolds via Ring Opening Michael Addition of Cyclic Nitroketene and Iminocoumarin: Synthesis and DFT Studies

Abstract

A novel strategy was developed for the synthesis of five different N-fused 1,4-dihydropyridine (1,4 DHP) scaffolds such as imidazopyridine, pyridopyrimidine, benzoimidazopyridine, thiazolopyridine and benzopyridooxazine derivatives by coupling nitroketene S,S-acetal, various nitrogen containing dinucleophiles, malanonitrile and substituted salicylaldehydes/aldehydes in the presence of InCl 3 as catalyst in water-EtOH solvent mixture under reflux condition. Furthermore, mechanism for the formation of 1,4-DHPs was explored through experimental and DFT calculations. DFT studies reveal that the reaction went through lower energy triheterocyclic intermediate than the higher energy chromenoimidazopyridine imtermediate. The attractive features of this protocol include short reaction time, easy separation of the product without chromatographic purification, simple execution with excellent yield and possibility to synthesize structurally diverse 1,4-dihydropyridine derivatives through greener approach.

Metal-Free and Regioselective Synthesis of Substituted and Fused Chromenopyrrole Scaffolds via the Divergent Reactivity of α-Azido Ketones in Water

“…Further, the synthesized pyrrole derivatives were successfully transformed into biologically significant 6-azaindole derivatives in an efficient manner. In this work, our aim is to develop a new synthetic methodology and explore the chemistry of α-azido ketones for synthesizing novel heterocyclic systems through domino one-pot reactions in a simple synthetic approach.…”

Facile One-Pot Synthesis and Anti-Microbial Activity of Novel 1,4-Dihydropyridine Derivatives in Aqueous Micellar Solution under Microwave Irradiation

“…But due to drawbacks such as harsh reaction conditions, long reaction time, and generally low yield of products, new modifications were made to it to obtain the targeted compounds,1,4-DHPs, in good to excellent yields [ 15 ]. It has been reported that in multicomponent reactions (MCRs), a wide variety of catalysts has been studied for the production of 1,4-DHP derivatives, encompassing various Lewis or Bronsted acids such as Y(OTf) 3 [ 16 ], free nano-Fe 2 O 3 [ 17 ], TMU-33 [ 18 ], InCl 3 [ 19 ]; heterogeneous catalyst such as HClO 4 –SiO 2 [ 20 ], PdRuNi@GO NPs [ 7 ], zeolite [ 21 ], IRMOF-3 [ 22 ]; organ catalyst, CAN [ 23 ], Montmorillonite K10 clay [ 24 ], HClO 4 -SiO 2 [ 25 ], tetrabutylammonium hydrogen sulfate, sodium- and Cs-Norit carbons, fermenting Baker’s yeast [ 26 ], metal triflates with the incorporation of numerous methodologies such as stirring [ 2 ], conventional heating [ 27 ], refluxing [ 22 ], microwave [ 1 ], visible light [ 4 ], and ultrasound irradiations [ 21 ]. Researchers are now focusing on the green aspects of this reaction leading to the usage of various green solvents such as glycerol [ 18 ], water [ 19 ], and ionic liquids [ 6 ].…”

Simple synthesis of new imidazopyridinone, pyridopyrimidinone, and thiazolopyridinone derivatives and optimization of reaction parameters using response surface methodology

“…The numerous attractive features of enamines or dienamines derived from the 1,1-bis(methylthio)-2-nitroethene have made them important intermediates for the construction of a wide variety of S-and N-heterocyclic systems. [27][28][29][30][31][32][33] Hence during recent years, they have been used for the synthesis of various fused heterocycles and drug-like compounds. For examples in 2013 Bazgir et al described a one-pot, four-component synthesis of a novel class of functionalized imidazo[1,2-a]pyridine derivatives starting from readily available inputs including diverse diamines, 1,1-bis(methylthio)-2-nitroethene, aldehydes and activated methylene compounds in EtOH under reux conditions (Scheme 1, Entry a).…”