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4.1 Introduction
There are only a few approaches that describe the direct synthesis of 2aminoimidazoles
and their biological activity 1-5 . The earliest method involves
condensation of α-aminocarbonyl compounds with cyanamide or their synthetic
equivalents 6,7 . This method is most commonly used for the direct construction of the
2-aminoimidazole ring. Other general applicable strategies are cyclocondensation of
α-bromoketone with N-acetylguanidine in acetonitrile 8 , iminophosphorane-mediated
cyclization of α –azido esters 9 , ammonolysis of 2-amino-1,3-oxazol-3-iumsalts 10 ,
sequential functionalization of 1,2-diprotected imidazole ring with different
electrophiles 11 . Most of them involve long experimental procedures, the use of
unstable precursors and tiresome workup process. Accordingly, the development of
straightforward and general procedures for the synthesis of diversely substituted 2aminoimidazoles
from readily available precursors is highly warranted. Herein, we
report a rapid and highly efficient Cu-mediated synthesis of 2-aminoimidazoletriazole
framework via click reaction and dimorth rearrangement.
“Click chemistry” has emerged as a fast and efficient approach to synthesis of novel
compounds with desired function making use of selected “near perfect” reactions. 12
(very fast, selective, high-yield, and wide scope).
The Dimroth rearrangement 13 is an isomerization of heterocycles that consists in a
translocation of endo- or exocyclic heteroatoms through a ring-opening-ring-closure
sequence. It can be catalyzed by acids, bases, heat or light.
Recently group of Erik 14 reported a new one pot microwave assisted synthesis of
substituted 2-amino-1H- imidazoles from readily available 2-aminopyrimidine (1) and
α-bromoketone (2). The first step was performed by heating N-(3azidopropyl)pyrimidin-2-amine
(1) and 2-bromo-1-phenylethanone (2) at 75 o C for 3
h resulting in the formation of hydroxyl salt (3) which undergoes dimorth type
rearrangement by 7 equiv of NH2NH2.H2O resulting in the formation of N-(2-azido)-
1H-imidazol-2-amine. Final step of click reaction was performed under microwaveirradiation
using phenylacetylene (1.5.equiv), Cu(Oac)2 (10 mol %)as catalyst at 100
o
C 10 min with a maximum power of 40W to obtain 2-AI-T scaffold (5). (Scheme 1)