Chemistry of Heterocyclic Compounds 2018, 54(3), 351–354
Scheme 2
In the conclusion, we present an efficient method for the
2-(4-Hydroxyphenyl)-1H-benzimidazole (3d). Yield
0.16 g (77%), pale-yellow solid, mp 254–255°C (mp 256°C22).
1H NMR spectrum, δ, ppm (J, Hz): 6.93 (2H, dd, J = 8.5,
J = 1.2, H Ar); 7.10–7.22 (2H, m, H Ar); 7.52–7.53 (2H,
m, H Ar); 8.02 (2H, d, J = 8.6, H Ar); 10.07 (1H, s, H Ar);
12.65 (1H, s, NH). 13C NMR spectrum, δ, ppm: 111.4;
115.7; 121.0; 121.6; 122.5; 128.1; 151.8; 159.1.
2-(4-Bromophenyl)-1H-benzimidazole (3e). Yield 0.24 g
(88%), colorless solid, mp 292–295°C (mp 299–300°C23).
1H NMR spectrum, δ, ppm (J, Hz): 7.22–7.24 (2H, m,
H Ar); 7.50–7.70 (2H, m, H Ar); 7.97 (2H, d, J = 8.3,
H Ar); 8.31 (2H, d, J = 8.3, H Ar); 13.17 (1H, s, NH).
13C NMR spectrum, δ, ppm: 111.8; 119.3; 122.2; 123.2;
126.9; 132.9; 134.2; 149.3.
2-(4-Chlorophenyl)-1H-benzimidazole (3f). Yield 0.19 g
(85%), colorless solid, mp 292–293°C (mp 292–294°C23).
1H NMR spectrum, δ, ppm (J, Hz): 7.18–7.21 (2H, m,
H Ar); 7.60–7.68 (4H, m, H Ar); 8.17 (2H, d, J = 8.6,
H Ar); 12.99 (1H, s, NH). 13C NMR spectrum, δ, ppm:
111.4; 118.9; 121.9; 122.7; 128.1; 129.0; 134.5; 150.1.
2-(2-Chlorophenyl)-1H-benzimidazole (3g). Yield 0.19 g
(83%), white crystals, mp 253–255°C (mp 233–234°C23).
1H NMR spectrum, δ, ppm (J, Hz): 7.25 (1H, s, H Ar); 7.27
(1H, s, H Ar); 7.57–7.52 (3H, m, H Ar); 7.67 (2H, dd, J = 8.4,
J = 1.2, H Ar); 7.92 (1H, dd, J = 7.8, J = 1.8, H Ar). 13C NMR
spectrum, δ, ppm: 127.9; 130.5; 130.8; 131.7; 132.1; 132.6; 149.6.
2-(4-Nitrophenyl)-1H-benzimidazole (3h). Yield 0.20 g
(84%), yellow solid, mp 302–304°C (mp 303–304°C20).
1H NMR spectrum, δ, ppm (J, Hz): 7.23–7.27 (2H, m,
H Ar); 7.63–7.65 (2H, m, H Ar); 8.36–8.65 (4H, m, H Ar);
13.26 (1H, s, NH). 13C NMR spectrum, δ, ppm: 119.3;
123.4; 124.1; 127.2; 129.6; 135.9; 147.6; 148.9.
preparation of 2-arylbenzimidazole derivatives. This
approach involves an SNAr reaction of 1-fluoro-2-nitro-
benzene with benzamidine hydrochloride derivatives in
DMSO at 120°C in the presence of CuBr as the catalyst.
The main advantages of this reaction include use of simple
and readily available starting materials, easy workup
procedure, and good to excellent product yields.
Experimental
1H and 13C NMR spectra were acquired on a Bruker
Avance 300 NMR spectrometer (300 and 75 MHz,
respectively) for solutions in DMSO-d6, using TMS as
internal standard. Melting points were determined in
capillaries and were not corrected. Merck silica gel 60 was
used for preparative column chromatography.
All reagents, solvents, and materials were purchased from
commercial suppliers and used without further purification.
Synthesis of benzimidazole derivatives 3a–h (General
method). A mixture of 1-fluoro-2-nitrobenzene (1) (0.141 g,
1.0 mmol), the appropriate benzamidine hydrochloride 2a–h
(1.0 mmol), CuBr (0.029 g, 0.2 mmol), and K2CO3 (0.276 g,
2.0 mmol) in dry DMSO (3.0 ml) was heated in a round-
bottom flask for 8 h at 120°C. After the reaction was
complete (TLC), the mixture was cooled, quenched with
water (20 ml), and extracted with EtOAc (3 × 20 ml). The
extract was washed with 20% aqueous NaCl solution, dried
over Na2SO4, and concentrated under reduced pressure.
The residue was purified by column chromatography using
petroleum ether – ethyl acetate, 4:1, as eluent to afford the
pure products.
2-Phenyl-1H-benzimidazole (3a). Yield 0.17 g (87%),
colorless solid, mp 282–284°C (mp 288–290°C20). 1H NMR
spectrum, δ, ppm (J, Hz): 7.14–7.25 (2H, m, H Ar); 7.44–7.61
(5H, m, H Ar); 8.20 (2H, d, J = 7.2, H Ar); 12.94 (1H, s,
NH). 13C NMR spectrum, δ, ppm: 122.1; 126.4; 128.4;
128.9; 129.2; 129.8; 130.1; 151.2.
The authors wish to thank the support of the Vice-
Chancellor for Research of Shiraz University of Medical
Sciences (grant No. 1396-01-12-14909).
2-(4-Methylphenyl)-1H-benzimidazole (3b). Yield 0.19 g
(90%), colorless solid, mp 270–272°C (mp 271°C21). 1H NMR
spectrum, δ, ppm (J, Hz): 2.35 (3H, s, CH3); 7.15–7.20
(2H, m, H Ar); 7.33 (2H, d, J = 8.1, H Ar); 7.46–7.56 (2H,
m, H Ar); 8.07 (2H, d, J = 8.1, H Ar); 12.84 (1H, s, NH).
13C NMR spectrum, δ, ppm: 20.9; 121.9; 126.3; 127.4;
128.4; 128.9; 129.4; 139.5; 151.3.
References
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12, 38.
2-(4-Methoxyphenyl)-1H-benzimidazole (3c). Yield
0.21 g (92%), colorless solid, mp 216–218°C (mp 223–
1
226°C21). H NMR spectrum, δ, ppm (J, Hz): 3.78 (3H, s,
CH3); 7.10 (2H, d, J = 8.8, H Ar); 7.16 (2H, dd, J = 3.1,
H Ar); 7.50–7.56 (2H, m, H Ar); 8.12 (2H, d, J = 8.8,
H Ar); 12.76 (1H, s, NH). 13C NMR spectrum, δ, ppm:
55.2; 111.0; 118.4; 121.5; 122.0; 122.6; 128.0; 151.3; 160.5.
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