Catalyst‐Free, Glycerol‐Assisted Facile Approach to Imidazole‐Fused Nitrogen‐Bridgehead Heterocycles

Abstract

A completely regioselective, environmentally benign strategy for the facile synthesis of biologically important imidazole‐fused nitrogen‐bridgehead heterocycles has been developed using glycerol/water 4:1 as a green promoting media. The methodology involves the simple coupling of 2‐halocarbonyl compounds with 2‐aminopyridines, 2‐aminopyrimidines, 2‐aminopyrazines to obtain a variety of 2‐aryl substituted imidazo‐pyridines, imidazo‐pyrimidines and imidazo‐pyrazines containing bridgehead nitrogen. This protocol eliminates the use of toxic catalysts and volatile organic solvents ‐ two key principles in the development of a green chemical process. Other significant highlights include mild reaction conditions, operational simplicity, short reaction times, easy workup and purification process, high yields and potential for scale‐up.

Deep Eutectic Solvent‐Mediated Regioselective Synthesis of Imidazoheterocycles

“…A plausible mechanism [ 35 ] for this protocol is shown in Figure . Initially, the nucleophilic attack of nitrogen of 2‐aminopyridine on the phenacyl bromide results in the formation of a new C‐N bond and in the later steps dehydrative condensation leading to the formation of the imidazo‐fused heterocyclic moiety.…”

Microwave‐assisted synthesis and luminescent activity of imidazo[1,2‐a]pyridine derivatives

“…On the other hand, Jadhav et al used water and polyethylene glycol as solvent in a one‐pot reaction avoiding the synthesis of the α‐halocarbonyl (Scheme B). In the same way, Tufail et al developed a green media using glycerol and water as solvent with the regioselective product in position 2 (Scheme C). On the other hand, He et al accomplished the product by an oxidative cross‐coupling/cyclization catalyzed by silver in nitrogen atmosphere (Scheme D), using alkynes as well.…”

Catalyst Free, Multicomponent Green Approach to Benzo[a]chromeno[2,3‐c]phenazines Using Glycerol as a Recyclable and Biodegradable Promoting Medium

“…[9][10][11] It has attributes of both water and ionic liquids, like easy availability, reusability, inexpensiveness, relatively low vapour pressure, low toxicity, high boiling point and the ability to dissolve a wide range of organic and inorganic compounds. [12,13] Because of these important properties glycerol is attracting increasing attention as a green and sustainable solvent cum promoter in the chemical and pharmaceutical industry. [14] Likewise, catalysts are another major source of pollution from chemical processes.…”

“…Among green solvents, glycerol – a bio‐renewable and bio‐degradable compound, obtained as a by‐product of the biodiesel industry has drawn considerable attention as a solvent in organic synthesis due to its unique properties and green credentials [9–11] . It has attributes of both water and ionic liquids, like easy availability, reusability, inexpensiveness, relatively low vapour pressure, low toxicity, high boiling point and the ability to dissolve a wide range of organic and inorganic compounds [12,13] . Because of these important properties glycerol is attracting increasing attention as a green and sustainable solvent cum promoter in the chemical and pharmaceutical industry [14] .…”