Synthesis of 3-Aroyl-4-heteroarylpyrrole Derivatives by the Van Leusen Method

Jairo Quiroga,Jorge Trilleras,Angelina Hormaza

doi:10.3390/m1341

Jairo Quiroga, Jorge Trilleras + Show 1 more

Open Access

https://doi.org/10.3390/m1341

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Abstract

The synthesis and structural diversification of N-heterocycles systems have attracted much attention because of their potential applications. Three 6-aryl-3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine-5-carbaldehyde 4 derivatives, in reaction with acetophenones 5, via conventional Claisen–Schmidt condensation reactions, generated the respective enones. The enones were used as electron-deficient olefins in a “formal” [2+3] cycloaddition reaction using p-tosylmethyl isocyanide—TosMIC 7. This protocol allows access to 3-(substituted aroyl)-4-heteroaryl pyrrole derivatives by the Van Leusen method.

Highlights

Pyrroles, π-excess N-heterocyclic systems, are found in nature, and several derivatives with interesting properties have been synthesized [1,2,3,4,5]
Because of the importance of pyrrole and its substituted derivatives as basic substructures in natural and synthetic products, the synthesis of these five-membered heterocycles is of interest to researchers
We extend the scope for the synthesis of 3,4-disubstituted pyrrole derivatives from pyrazolo[3,4-b]pyridine-based chalcones

Summary

Introduction

Π-excess N-heterocyclic systems, are found in nature, and several derivatives with interesting properties have been synthesized [1,2,3,4,5]. A variety of methodologies have been reported, including variations to the classical condensation reactions (Hantzsch, Knorr, and Paal–Knorr); heterocyclization reactions of alcohol, N-propargylamine, and α-iminodiazoacetates motifs [6]; the Barton–Zard procedure via coupling cyclization reaction between nitro-acetates and isocyanides; and the reaction of Van Leusen, starting with chalcones as electron-deficient olefins in a [2+3] heterocyclization with p-toluenesulfonyl methylisocyanide-TosMIC as a three-atom synthon and nitrogen source [6,7,8]. The TosMIC reagent is a versatile and powerful synthetic tool in heterocyclization reactions to build five- and six-membered heterocycles and heterofused systems. In reaction to the structural diversity of heterocyclic analogs of chalcones [9,10], TosMIC allows access to the polysubstituted or condensed pyrrole derivatives with different types of substituents—simple or complex—and has potential applications in the fields of chemistry and medicine [11,12,13]

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