(1.0 mmol) in CH3CN (5 mL), and the resulting solution was stirred
for 10 min at room temperature. Solvent was evaporated, then the
residue was washed with water and extracted with EtOAc (2 × 15
mL). The organic phase was dried over MgSO4 and concentrated
under vacuum to give thioether S-alkylated product up to 98% yield,
which was used for the next step without any further purification.
(In the case of BnBr, p-(MeO)C6H4CH2Br, and p-(NO2)C6H4CH2Br,
1 mmol of halide were used and the reaction time was extended to
20 min).
2-(4-Methoxybenzylthio)-1-phenylbenzimidazole (2s): color-
less gum; H NMR (250 MHz, CDCl3) δ 3.63 (s, 3H), 4.48 (s,
1
2H), 6.67-6.71 (d, 2H, J ) 8.6 Hz), 7.04-7.40 (m, 10H), 7.67 (d,
1H, J ) 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ 41.5, 60.4, 114.7,
119.2, 123.3, 124.0, 127.5, 127.6, 132.0, 134.2, 135.0, 135.6, 137.6,
140.3, 142.4, 148.7, 157.4, 164.3; IR (KBr) 3062, 2955, 2933, 2834,
1610, 1513, 1434, 1269, 1244, 1028, 832, 744 cm-1. Anal. Calcd
for C21H18N2OS: C, 72.80; H, 5.24; N, 8.09; S, 9.26. Found C,
73.02; H, 5.25; N, 8.14; S, 9.32.
A round-bottomed flask was charged with thioether S-alkylated
product (∼1 mmol), CuI (0.05 mmol, 9.5 mg), 1,10-phenanthroline
(0.1 mmol, 18 mg), K2CO3 (2 mmol, 276 mg), and 1,4-dioxane (5
mL). The resulting solution was heated at 85 °C until the
disappearance of the starting material (TLC). The reaction mixture
was then cooled and filtered over Celite with EtOAc. Solvent was
evaporated and further purification was achieved by column
chromatography.
General Procedure for the Synthesis of Benzimidazole
Thiones 3. Thiourea 1 (1.0 mmol) was first alkylated as described
above. A round-bottomed flask was charged with the corresponding
thioether S-alkylated product (∼1.0 mmol), CuI (0.05 mmol, 9.5
mg), 1,10-phenanthroline (0.1 mmol, 18 mg), K2CO3 (2.0 mmol,
276 mg), and 1,4-dioxane (5 mL). The resulting solution was heated
at 85 °C until the disappearance of the starting material (TLC).
The reaction mixture was then cooled and filtered over Celite with
EtOAc, then solvent was evaporated. TFA (3-5 mL) was added,
and the reaction mixture was heated at 85 °C for 2 h. After
completion, TFA was removed under vacuum and the residue was
treated with sodium bicarbonate solution. The product was extracted
with EtOAc (2 × 15 mL). The organic phase was dried over MgSO4
and then evaporated. The crude product was purified with a short
chromatography column.
1-Phenylbenzimidazole-2-thione (3a): white solid; mp 160-163
°C; 1H NMR (250 MHz, CDCl3/DMSO-d6) δ 6.96 (d, 1H, J ) 7.5
Hz), 7.21-7.34 (m, 3H), 7.58-7.71 (m, 5H), 13.12 (s, 1H); 13C
NMR (100 MHz, CDCl3/DMSO-d6) δ 109.0, 122.1, 122.8, 126.8,
128.2, 128.6, 134.1, 136.4, 137.6, 138.8, 167.7; IR (KBr) 3138,
3052, 2985, 2926, 1595, 1500, 1462, 1445, 1217, 735 cm-1. Anal.
Calcd for C13H10N2S: C, 69.00; H, 4.45; N, 12.38; S, 14.17. Found:
C, 69.14; H, 4.46; N, 12.43; S, 14.26.
2-(Methylthio)-1-phenylbenzimidazole (2a): colorless gum; 1H
NMR (250 MHz, CDCl3) δ 2.63 (s, 3H), 7.06 (m, 3H), 7.36 (m,
5H), 7.64 (d, 1H, J ) 8.0 Hz); 13C NMR (100 MHz, CDCl3) δ
13.8, 108.4, 117.2, 121.4, 126.0, 128.1, 129.0, 134.4, 136.6, 142.7,
152.6; IR (KBr) 3052, 2928, 2853, 1596, 1499, 1369, 1270, 1011,
741 cm-1. Anal. Calcd for C14H12N2S: C, 69.97; H, 5.03; N, 11.66;
S, 13.34. Found: C, 69.81; H, 5.02; N, 12.02; S, 13.25.
2-(Methylthio)-1-p-tolylbenzimidazole (2b): white solid; mp
1
72-74 °C; H NMR (250 MHz, CDCl3) δ 2.37 (s, 3H), 2.66 (s,
3H), 7.04-7.29 (m, 7H), 7.65 (d, 1H, J ) 7.6 Hz); 13C NMR (100
MHz, CDCl3) δ 13.0, 19.7, 107.7, 116.3, 120.6, 125.1, 128.8, 136.0,
137.6, 141.9, 152.1; IR (KBr) 3056, 3029, 2922, 2858, 1604, 1514,
1445, 1270, 811, 744 cm-1. Anal. Calcd for C15H14N2S: C, 70.83;
H, 5.55; N, 11.01; S, 12.61. Found: C, 70.97; H, 5.57; N, 11.06; S,
12.69.
2-(Methylthio)-1-benzylbenzimidazole (2l): white solid; mp
1
77-79 °C; H NMR (250 MHz, CDCl3) δ 2.81 (s, 3H), 5.28 (s,
2H), 7.15-7.31 (m, 8H), 7.71 (d, 1H, J ) 7.6 Hz); 13C NMR (100
MHz, CDCl3) δ 15.3, 48.0, 109.4, 118.6, 122.4, 122.4, 127.4, 128.4,
129.3, 136.0, 136.9, 144.1, 153.6; IR (KBr) 3031, 2932, 2858, 1606,
1493, 1453, 1427, 1374, 1243, 995, 734 cm-1. Anal. Calcd for
C15H14N2S: C, 70.83; H, 5.55; N, 11.01; S, 12.61. Found: C, 70.98;
H, 5.58; N, 11.08; S, 12.76.
Acknowledgment. We are indebted to EGIDE for a Ph.D.
studentship to S.M. B.K.P. acknowledges support from DST
New Delhi (SR/S1/OC-15/2006) and CSIR 01(1688)/00/EMR-
II.
Supporting Information Available: General information and
preparation of 2-halothioureas and analytical data of compounds
2c-k, 2n-r, 2t-w, 2y, 3b, 3e, and 3h and copies of 1H NMR
and 13C NMR spectra for all new products. This material is
2-(Methylthio)-1-(furan-2-ylmethyl)benzimidazole (2m): brown
oil; 1H NMR (250 MHz, CDCl3) δ 2.70 (s, 3H), 5.11 (s, 2H), 6.20
(s, 2H), 7.09-7.23 (m, 4H), 7.58 (m, 1H); 13C NMR (100 MHz,
CDCl3) δ 14.0, 39.1, 108.0, 109.6, 117.2, 121.0, 121.1, 127.0, 131.6,
135.2, 142.0, 147.7, 153.6; IR (KBr) 3118, 3055, 2930, 1612, 1518,
1444, 1367, 1258, 1147, 1012, 923, 740 cm-1. HRMS (ESI) calcd
for C13H13N2OS (M + H)+ 245.0749, found 245.0754.
JO802589D
2220 J. Org. Chem. Vol. 74, No. 5, 2009