Acid-Catalyzed Multicomponent Rearrangements via 2-((Quinoxalin-3(4H)-on-2-yl)(aryl)methylene)malononitriles, Generated In Situ, for Divergent Synthesis of Pyrroles with Different Substitution Patterns

Abstract

New three-component domino reactions, providing divergent approaches to multifunctionalized pyrroles with different substitution patterns, have been established (47 examples). In this work, a new rearrangement of quinoxalinones with the participation of the in situ-generated 2-en-1-imine moiety of the substituent at C3 makes it possible to construct two new heterocyclic systems, namely, a benzimidazolone and a pyrrole, simultaneously under one-pot reaction conditions. The reaction is easy to perform simply by mixing three common reactants of acetic acid with heating. Secondary amines or primary alcohols as the third component of the reaction, along with quinoxalin-3­(4H)-ones and malononitrile, not only initiate the rearrangement but also are responsible for the nature of substituents at position 5 of the pyrrole ring in the newly formed new biheterocyclic system. The reaction proceeds smoothly and can be finished within 7 h, which makes workup convenient to give up to 97% chemical yields.

Mechanistic Insights for Acid‐catalyzed Rearrangement of Quinoxalin‐2‐one with Diamine and Enamine

“…In 2000, we discovered the acid‐catalyzed rearrangement of 3‐aroylquinoxalin‐2‐ones into 2‐(benzimidazol‐2‐yl)quinoxalines when exposed to 1,2‐benzenediamines [8] . In the last two decades, we have published a series of works on the rearrangement of quinoxalin‐2‐ones via the proposed spiro‐quinoxalinone [9] intermediates ( A ) into 2‐hetarylbenzimidazoles [9a–h] ( B , Type I) as well as 1‐hetarylbenzimidazolones in cases of enamine nucleophiles ( C , Type II, Scheme 1), [9i–k] thus opening a simple way to access various 2‐hetarylbenzimidazoles and 1‐hetarylbenzimidazolones according to the S N (ANRORC) mechanism (i. e., via sequential steps of addition of nucleophile, ring‐opening and ring‐closing) [10] . It was shown that the type of rearrangement may depend on the fact if tautomerizable hydrogen is available or not in the spiro‐forming ring within A .…”

Synthetic Applications of Ambiphilic C‐acylimines in Organic Synthesis

“…A. Mamedov and coworkers reported a novel threecomponent domino reaction allowing for multiple approaches to multi-functionalized pyrroles 75 with diverse substitution patterns. [27] The reaction is simple to carry out, requiring only mixing three common reactants and high temperature. Along with quinoxalin-3(4H)-ones 72 and malononitrile 73, secondary amines 74 were used as the third component of the reaction, which is responsible for the type of substituents at 5 th position of the pyrrole ring.…”

“…V. A. Mamedov and coworkers reported a novel three‐component domino reaction allowing for multiple approaches to multi‐functionalized pyrroles 75 with diverse substitution patterns [27] . The reaction is simple to carry out, requiring only mixing three common reactants and high temperature.…”

Recent Advances for the Synthesis of N‐Unsubstituted Pyrroles

“…et al (Scheme 61). [60] The reaction mechanism involves Knoevenagel condensation of quinoxalinones 184 with malononitrile followed by in situ generation of 2-en-1imine under nucleophile action. The intermediate B undergoes Intramolecular cyclization and rearrangement allowing to ChemistrySelect construct heterocyclic systems, containing pyrrole and benzimidazolone cores.…”