Method for arylation of the amino group in N-aminoazoles [3]

Full text of DOI:10.1023/A:1019533818316

Chemistry of Heterocyclic Compounds, Vol. 38, No. 5, 2002
METHOD FOR ARYLATION OF THE
AMINO GROUP IN N-AMINOAZOLES
O. V. Dyablo, A. F. Pozharskii, and M. G. Koroleva
Keywords: N-aminoazoles, phenylboric acid, arylation, Suzuki reaction.
The direct arylation of the N-amino group in N-aminoazoles proceeds much less readily than the
corresponding alkylation reaction [1-3]. All the reported examples of such arylation reactions have involved the
use of aryl halides activated by strong electron-withdrawing groups such as NO2 or CN. Thus, in particular,
some 2-(arylamino)benzotriazoles [4], 1-(arylamino)benzimidazoles [5], and 1-(arylamino)-1,2,4-triazoles were
obtained [6]. Following the recent report of the N-arylation of arylamines using arylboric acids by a
modification of the Suzuki reaction [7], we studied the use of such a procedure for N-aminoazoles. The amino
groups in arylamines and N-aminoazoles differ in their geometry and interaction with the aromatic π-system [1].
Thus, it was impossible to predict the result of these experiments.
The reaction of 1-aminobenzimidazole (1) with phenylboric acid in the presence of Cu(OAc)2 and Et3N
gave previously unreported 1-phenylaminobenzimidazole (2) in 18% yield. Analogously, 2-methyl-1-
phenylaminobenzimidazole (3) as well as 1- (4) and 2-phenylaminoindazoles (5) were obtained from the
corresponding amines. Despite the low yields (16-29%), this method appears useful since there are presently no
other methods for the preparation of N-phenylaminoazoles. For example, we were unable to obtain 2 by the
arylation of amine 1 through the Ullmann reaction or heating the potassium salt of 1-formylaminobenzimidazole
with halobenzenes. On the other hand, the Suzuki reaction is probably limited to N-aminoazoles. Thus, only the
starting amine was obtained in an attempt to arylate 1-aminobenzotriazole by phenylboric acid.
N
N
PhB(OH)2
N
N
Cu(OAc)2, Et3N, CH2Cl2
20 oC
NH2
NHPh
2
1
N
N
N
N NHPh
Me
NHPh
N
NHPh
4
N
5
3
General Method for the Synthesis of N-Phenylaminoazoles. A sample of anhydrous cupric acetate
(0.182 g, 1 mmol), phenylboric acid (0.244 g, 2 mmol), and Et3N (0.14 ml, 1 mmol) were added to a solution of
N-aminoazole (1 mmol) in a minimal amount of CH2Cl2 (3-10 ml). The mixture was stirred at 20°C for 17-96 h
until the starting compound disappeared as indicated by thin-layer chromatography. The solvent was distilled
__________________________________________________________________________________________
Rostov State University, 344090 Rostov-on-Don, Russia; e-mail: ODyablo@chimfak.rsu.ru. Translated
from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 705-707, May, 2002. Original article submitted
February 6, 2002.
620
0009-3122/02/3805-0620$27.00©2002 Plenum Publishing Corporation

off and the dry residue was extracted with 10 ml chloroform. The extract was passed through a 25-cm alumina
column (d = 1.5 cm), collecting the fraction with Rf 0.4-0.6. Evaporation of the chloroform gave white
crystalline N-phenylaminoazoles.
1-Phenylaminobenzimidazole (2) was obtained in 18% yield after 70 h; mp 203-205°C (ethyl acetate).
IR spectrum in vaseline mull, νNH, cm-1: 3166. 1H NMR spectrum (CDCl3, 250 MHz), δ, ppm: 6.59 (2H, m, 2'-,
6'-H); 6.87 (1H, br. s, NH); 6.95 (1H, m, 4'-H); 7.26 (5H, m, 4-, 5-, 6-, 3'-, 5'-H); 7.74 (1H, m, 7-H); 8.05 (1H, s,
2-H).
2-Methyl-1-phenylaminobenzimidazole (3) was obtained in 27% yield after 96 h; mp 225-227°C
1
(acetonitrile). IR spectrum in vaseline mull, νNH, cm-1: 3193. H NMR spectrum (CDCl3, 250 MHz), δ, ppm:
2.55 (3H, s, CH3); 6.54 (2H, m, 2'-, 6'-H); 6.63 (1H, br. s, NH); 6.94 (1H, m, 4'-H); 7.20 (5H, m, 4', 5', 6'-, 3'-,
5'-H); 7.70 (1H, m, 7-H).
1-Phenylaminoimidazole (4) was obtained in 29% yield after 17 h; mp 139-140°C (octane). IR
1
spectrum in vaseline mull, νNH, cm-1: 3190. H NMR spectrum (CDCl3, 250 MHz), δ, ppm: 6.48 (2H, m, 2'-,
6'-H); 6.92 (1H, m, 4'-H); 7.10 (1H, br. s, NH); 7.19 (3H, m, 5-, 3'-, 5'-H); 7.41 (1H, m, 6-H); 7.52 (1H, m, 4-H);
7.74 (1H, m, 7-H); 8.03 (1H, d, J = 0.66 Hz, 2-H).
2-Phenylaminoindazole (5) was obtained in 16% yield after 17 h; mp 140-142°C (octane). IR
1
spectrum in vaseline mull, νNH, cm-1: 3180. H NMR spectrum (CDCl3, 250 MHz), δ, ppm: 6.51 (2H, m, 2'-,
6'-H); 6.95 (1H, m, 4'-H); 7.16 (3H, m, 5-, 3'-, 5'-H); 7.33 (1H, m, 6-H); 7.68 (2H, m, 4-, 7-H); 7.72 (1H, br. s,
NH); 8.12 (1H, d, J = 0.77 Hz, 2-H).
REFERENCES
1.
2.
3.
V. V. Kuzmenko and A. F. Pozharskii, Advances in Heterocyclic Chemistry, Vol. 53 (1992), p. 85.
V. V. Kuzmenko, I. A. Filatova, and A. F. Pozharskii, Khim. Geterotsikl. Soedin., 1196 (1992).
O. V. Dyablo, A. F. Pozharskii, and V. V. Kuzmenko, Izv. Rossiisk. Akad. Nauk, Ser. Khim., 2231
(1995).
4.
5.
R. A. Carboni, US Patent No. 3,184,472; Chem. Abstr., 63, 4306 (1965).
A. F. Pozharskii, O. V. Dyablo, V. V. Kuzmenko, and E. Yu. Evgrafova, Khim. Geterotsikl. Soedin.,
1347 (1996).
6.
7.
M. Okada, T. Yoder, E. Kawaminami, Y. Shimada, M. Kudoh, and Y. Isomura, Chem. Pharm. Bull., 45,
333 (1997).
D. M. T. Chan, K. L. Monaco, R.-P. Wang, and M. P. Winters, Tetrahedron Lett., 39, 2933 (1998).
621