Catalyst-Free Preparation of 1,2,4,5-Tetrasubstituted Imidazoles from a Novel Unexpected Domino Reaction of 2-Azido Acrylates and Nitrones

Abstract

A highly efficient and convenient method for the synthesis of 1,2,4,5-tetrasubstituted imidazoles from readily accessible 2-azido acrylates and nitrones has been developed. This reaction proceeded under mild conditions without the assistance of any metal, acid, or base.

Metal‐Free [2+2+1] Annulation of Alkynes, Nitriles and Nitrogen Atoms from Iminoiodanes for Synthesis of Highly Substituted Imidazoles

“…[4] Therefore, the wide applicability of this heterocycle has still encouraged the development of efficient and versatile approaches to functionalized imidazoles. [5,6] As one of attractive synthetic methods for a diversity of target molecules, the metal-catalyzed [2+2+1] annulation of alkynes, nitriles and nitrogen atoms from azides was known (Scheme 1a). [7] The method, however, can stand further improvement due to the requirements of high reaction temperature and tedious procedures, and the limitation of the substrate generality (terminal alkynes only).…”

One-pot synthesis of 1,2,4,5-tetrasubstituted imidazoles by a tandem three-component reaction of hydroxylamines, aldehydes and 2-azido acrylates

“…13 The first experiment was set up as follows: hydroxylamine 4a (3.0 equiv), p-Bromobenzaldehyde 5a (3.0 equiv), and anhydrous MgSO 4 (4.0 equiv) were combined and stirred overnight in DCE at room temperature. After the nitrone 1a was formed completely, 2-azido acrylate 2a (1.0 equiv) was added, and the reaction mixture was stirred at 65-70 °C for 72 h. This afforded 3a in 60% isolated yield ( Table 1, entry 1).…”

“…For benzyl-substituted 2-azido acrylate, the corresponding imidazole product 3u was obtained in 42% yield, which is similar to our previous reports. 13 Instead of α-ethoxycarbonyl-substituted vinyl azides, the reaction of vinyl azide bearing an acetyl or a formyl group at the α-position gave the desired products with lower yields.…”

Iron(III)/Iodine‐Catalyzed C(sp2)H Activation of α,β‐Unsaturated Aldehydes/Ketones with Amidines: Synthesis of 1,2,4,5‐Tetrasubstituted Imidazoles

“…[13] In 2011, Wang and co-workers reported the use of 2-azidoacrylatesa nd nitrones to synthesize 1,2,4,5-tetrasubstituted imidazoles. [14] Subsequently, Bhuvanesh and co-workers preparedh ighly substituted imidazoles from Er(OTf) 3 -catalyzed reaction of aazidochalconesa nd aryl aldehydesi n2 013. [15] Althoughe ffective as they are,t hey may suffer from some drawbackss uch as complex starting materials, low yields,p oor atom economy and poorly accessible synthetic precursors.…”