Acetic Acid Catalysed One-Pot Synthesis of Pyrrolo[1,2-a]quinoxaline Derivatives

Abstract

An efficient acetic acid catalysed reaction has been developed for the synthesis of 4-aryl substituted pyrrolo[1,2-a]quinoxalines from readily available starting materials. A range of structures have been synthesised in very good to excellent yields. The one-pot reaction proceeds through imine formation, cyclisation followed by air oxidation.

Novel Synthetic Routes to Prepare Biologically Active Quinoxalines and Their Derivatives: A Synthetic Review for the Last Two Decades

“…Various synthetic pathways have been developed to prepare pyrroloquinoxalines [42][43][44] because it is crucial in drug discovery. For this reason, an efficient method was established by Allan et al [45], which is an acid-catalyzed reaction for the synthesis of 4-aryl substituted pyrrolo[1,2-a] quinoxalines (24). This one-pot reaction involves imine formation, followed by cyclization and air oxidation.…”

“…Xia et al [57] synthesized a series of penta-1,4-dien-3-one oxime comprising a quinoxaline moiety, equivalent to curcumin isolated from plant Curcuma Longa L. The synthesized compounds displayed antibacterial and antiviral activities, with distinct activity against TMV. As revealed in Scheme 13, 2-chloroquinoxaline (43) and penta-1,4-dien-3-one oxime ether (44) were stirred for 30 min and refluxed for 4 h at 80 • C to get the target compound (45). The product is recrystallized with acetonitrile and dichloromethane.…”

Recent advances in the transition-metal-free synthesis of quinoxalines

“…In 2019, Patel et al reported an efficient acetic acid-catalyzed synthesis of pyrrolo[1,2- a ]quinoxalines 87 via a Pictet–Spengler type reaction of 2-(1 H -pyrrol-1-yl)aniline 78 to aldehyde 86 ( Scheme 28 ). 101 With only 10 mol% of AcOH acid as the catalyst, a total of 16 compounds were synthesized in 82–89% yields. Pleasingly, various substituted and unsubstituted 2-(1 H -pyrrol-1-yl)aniline 78 underwent the reaction smoothly to provide the desired product efficiently.…”

Efficient synthesis of pyrrolo[1,2-α]quinoxalines mediated by ethyl 2-(4-nitrophenyl)azocarboxylate

“…The classical methods are the Bischler–Napieralski type reactions of N -(2-acylaminophenyl)-pyrroles using dehydrating reagents such as POCl 3 (Scheme 1A). 14 The most common methods are Pictet–Spengler type reactions between 2-(1 H -pyrrol-1-yl)anilines and cyclization partners such as aldehydes, 15 alcohols, 16 amines, 17 alkyl halides, 18 ketones, 19 1,3-diketones, 20 α-keto acids, 21 α-hydroxyl acids, 22 α-amino acids, 23 aryl acetic acids, 24 cyclic ethers, 25 and methyl arenes 26 in the presence of various oxidants (Scheme 1B). 27,28 Although these oxidants facilitated Pictet–Spengler type pyrrolo[1,2-α]quinoxaline synthesis, a high reaction temperature was usually required and the substrate scope was mostly limited to 4-aryl substituted pyrrolo[1,2-α]quinoxalines.…”