Amides compund without naaj

amidi ne hydrochl orides were found to react with 2-ha loacetan ilides to give
benzimid azoles as well.255 The protocol uses 10 mol% CuBr as the catalyst,
Cs2CO3 as the base, and DMSO as the solvent; no ligand was required. The
procedure proceeds via the sequential coupling of o-haloacetoanilide derivatives
with amidines, hydrolysis of the intermediates (amides), and
intramolecular cyclization with the loss of NH3 to give 2-substituted
1Hbenzimidazoles (Scheme 2.132b). Zhou and co-workers found that the reaction
between 2-haloaniline and amidine hydrochlorides can provide the
same products as well.256 In this case, Cu2O was used as a catalyst and
DMEDA (N,N0-dimethylethane) as a ligand, with Cs2CO3 as a base in DMF
and the reaction was heated to 140 1C. In 2009, Glorius and co-workers reported a
copper-catalyzed cyclization of 2-bromoarylamidines to substituted
benzimidazoles (Scheme 2.132c).257 This procedure was studied further with
CuO nanoparticles as a catalyst under ligand-free conditions. 258 Additionally, this
catalyst was explored in the cyclization of o-bromoarylguanidine to
2-aminobenzimidazoles; o-bromoarylthiourea to 2-aminobenzothiazoles and
o-bromoanilide to 2-arylbenzoxazoles. An intermolecular version based on
2-bromoaniline and imidoyl chlorides was reported as well.259 In the presence of
CuI/1,10-Phen, with Cs2CO3 as a base, NMP as a solvent, at 100 1C,
the transformation proceeded smoothly. In 2011, a copper-catalyzed cyclization of
N-(2-haloaryl)benzamidines was described (Scheme 2.132d).260
With Cu2O (5 mol%) as the catalyst, DMEDA (10 mol%) as the ligand, and
K
2CO3 as the base, benzimidazoles were formed in high yields. Remarkably,
the reaction was exclusively carried out in water as the solvent. In 2007,
Buchwald and Zheng reported a copper-catalyzed procedure for the preparation of
N-alkylbenzimidazoles in regioisomerically pure form starting
from o-haloanilines.261 The method utilizing CuI and trans-N,N0-dimethyl-
1,2-cyclohexanediamine allows the preparation of N-alkylbenzimidazoles in
good to excellent yields (Scheme 2.132e). Recently, the usage of 2-iodoanilines and
benzamides to the corresponding 2-substituted benzimidazoles
was developed.262 Based on the CuI/DMEDA-catalyzed coupling reaction and
post-cyclization with glacial acetic acid, a variety of benzimidazoles were
isolated in moderate to good yields in short reaction times. In 2011, Lees
group found that benzimidazoles could be synthesized by the coppercatalyzed, one-
pot, three-component reaction of 2-haloanilines, aldehydes,
and NaN3.263 The reaction was optimized when 2-iodo- or 2-bromoanilines
(1.0 equiv.), aldehydes (1.2 equiv.), NaN3 (2.0 equiv.), 5 mol% of CuCl, and
5 mol% of TMEDA were reacted in DMSO at 120 1C for 12 h. Good yields
resulted, and the reaction showed tolerance toward functional groups such
as ester, nitro, and chloro. Aliphatic and heteroaromatic aldehydes also
afforded the desired products in moderate to good yields (Scheme 2.132f).
The reaction was proposed to start with condensation of 2-haloaniline and
aldehyde affording 2-halobenzimine. Then copper-catalyzed coupling of
2-halobenzimine with azide gave the final product. The reaction between
sulfonyl azides, alkynes, and 2-bromoanilines with CuI as a catalyst was
reported to give benzimidazole derivatives as well.264 Moderate to g