Copper‐Catalyzed Construction of Trinuclear N‐Fused Hybrid Scaffolds Using Cyclic Ureas as New Building Blocks

Abstract

2‐(2‐Bromoaryl)‐ and 2‐(2‐bromovinyl)‐benzimidazoles are coupled and cyclized with cyclic ureas as new building blocks in dimethylformamide in the presence of a catalytic amount of a copper catalyst and a base to give the corresponding trinuclear N‐fused hybrid scaffolds in good yields. Trinuclear N‐fused hybrid scaffolds having methoxy group on benzimidazole moiety are readily oxidized to unprecedented benzimidazolequinone‐fused hybrid scaffolds in high yields by treatment of ceric ammonium nitrate in acetonitrile/H2O.

Synthesis of Trinuclear Benzimidazole‐Fused Hybrid Scaffolds by Transition Metal‐Free Tandem C(sp2)−N Bond Formation under Microwave Irradiation

“…Treatment of acyclic 2‐(2‐bromovinyl)imidazoles 4 h – k with 2‐methoxybenzimidazoles ( 2 a – c and 2 f ) also triggers coupling and cyclization to produce the corresponding trinuclear N‐fused hybrid scaffolds 5 j – p in similar yields, irrespective of the identity of substituents on vinyl moiety and the kind of 2‐methoxybenzimidazoles. In contrast to limited synthetic methods of trinuclear scaffolds like 5 a – g , no reports have been found for those of trinuclear scaffolds like 5 i – p [11,21] …”

“…Here again, from the reaction of 1 k with 2‐methoxybenzimidazoles ( 2 b , 2 c and 2 f ), the corresponding trinuclear N‐fused hybrid scaffolds 3 r – t were also formed in 60–68 % yields. To the best of our knowledge, limited examples are found for the synthetic method of such a trinuclear N‐fused hybrid scaffold like 3 k – t [11,12] …”

“…The products were isolated by TLC (a glass plate coated with Kieselgel 60 GF 254 , Merck). The starting compounds 1 , 4 and building blocks 2 were prepared by known methods [11,14,15,25] . Other commercially available organic and inorganic reagents were used without further purification.…”

“…Benzo[4,5]imidazo[1,2‐ a ]benzo[4,5]imidazo[1,2‐ c ]quinazoline‐13‐carbonitrile (3 g) [11] . Purified by TLC (dichloromethane/MeOH=99/1, 2 times); white solid (56 mg, 56 %); mp 313–316 °C.…”

“…Such a similar construction of scaffold A using benzimidazole as a building block was also exemplified by Pd‐catalyzed C(sp 2 )−N coupling and cross‐dehydrogenative C(sp 2 )−H/N−H coupling between 2‐phenylbenzimidazole and benzimidazole (Scheme 1, route c) [9] . During the course of our recent efforts directed toward copper‐catalyzed and transition metal‐free synthesis of polynuclear N‐fused hybrid scaffolds via a C(sp 2 )−N coupling, we also recently reported that 2‐(2‐bromophenyl)benzimidazoles were coupled and cyclized with cyclic ureas as building blocks in the presence of CuI to produce scaffold A (Scheme 1, route d) [10,11] . In contrast to these precedents, the first transition metal‐free construction of scaffold A was achieved by a base‐mediated nucleophilic aromatic substitution (S N Ar) between 2‐(2‐bromophenyl)benzimidazoles and 2‐aminobenzimidazoles as building blocks (Scheme 1, route e) [12,13] .…”