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G. Navarrete-Vazquez et al. / Bioorg. Med. Chem. 11 (2003) 4615–4622
4619
7.65 (d, 1H, H-7, J=8.85 Hz), 7.69 (d, 1H, H-4, J=1.65
Hz), 10.86 (bs, 1H, N-H) ppm; 13C NMR (75.5 MHz,
CDCl3) d 13.27 (CH3CH2), 22.38 (CH3CH2CH2), 36.68
(CH2CH2S), 116.53 (C-4), 116.92 (C-7), 118.72 (q, CF3,
J=270.96 Hz), 127.34 (C-6), 133.91 (C-5), 136.29 (C-
7a), 137.58 (C-3a), 141.16 (q, C-2, J=40.77 Hz) ppm;
MS: m/z (% rel. int.) 260 (M+, 100), 231 (78), 218 (95),
187 (50); HRMS: calcd for C11H11F3N2S: 260.0595,
found: 260.0595.
H-6, J=8.40, J=1.50 Hz), 7.94 (d, 1H, H-7, J=8.40
Hz), 8.01 (d, 1H, H-4, J=0.90 Hz) ppm; 13C NMR
(75.5 MHz, CDCl3) d 31.14 (N-CH3), 112.82 (C-7),
118.74 (q, CF3, J=272 Hz), 121.10 (C-6), 125.79 (C-6),
128.36 (C-30, C-50), 130.01 (C-20, C-60), 132.53 (C-4),
134.77 (C-40), 135.80 (C-5), 137.66 (C-10, C-3a), 143.29
(q, C-2, J=39.48 Hz), 143.63 (C-7a), 196.14 (C¼O)
ppm; MS: m/z (% rel. int.) 304 (M+, 90), 227 (100), 199
(20); HRMS: calcd for C16H11F3N2O: 304.0823, found:
304.0832.
1-Methyl-6-(propylthio)-2-(trifluoromethyl)-1H-benzimi-
dazole (4b). Eluted with CHCl3 and recrystallized from
cyclohexane. Yield 7.46 g (87%) of white solid. Mp 55–
56.9 ꢁC. 1H NMR (300 MHz, CDCl3) d 1.05 (t, 3H,
CH3CH2), 1.71 (m, 2H, CH3CH2CH2), 2.97 (t, 2H,
CH2CH2S), 3.93 (s, 3H, N-CH3), 7.39 (dd, 1H, H-5,
J=8.40, J=1.80 Hz), 7.43 (d, 1H, H-7, J=1.50 Hz),
7.78 (d, 1H, H-4, J=8.10 Hz,) ppm; 13C NMR
6-Benzoyl-1-methyl-2-(trifluoromethyl)-1H-benzimidazole
(20). Eluted with CHCl3 and recrystallized from hexane.
Yield 7.71 g (81%) of white solid. Mp 156.8–158.1 ꢁC.
1H NMR (300 MHz, CDCl3) d 4.0 (s, 3H, N-CH3),
7.46–7.63 (m, 4H, H-20,H-30, H-50, H-60), 7.79–7.82 (m,
2H, H-4, H-40, J=8.40 Hz), 8.06 (dd, 1H, H-5, J=8.70,
J=1.80 Hz), 8.29 (d, 1H, H-7, J=0.90 Hz) ppm; 13C
NMR (75.5 MHz, CDCl3) d 31.15 (N-CH3), 110.36 (C-
7), 118.74 (q, CF3, J=271.80 Hz), 125.15 (C-5), 127.02
(C-4), 128.28 (C-30, C-50), 129.98 (C-20, C-60), 132.37 (C-
40), 133.38 (C-10), 137.680 (C-6), 138.66 (C-7a), 140.10
(C-3a), 142.60 (q, C-2, J=39.10 Hz), 196.01 (C¼O)
ppm; MS: m/z (% rel. int.) 304 (M+, 70), 227 (100), 199
(15); HRMS: calcd for C16H11F3N2O: 304.0823, found:
304.0844.
(75.5 MHz, CDCl3)
d
13.33 (CH3CH2), 22.46
(CH3CH2CH2), 30.76 (N-CH3), 36.78 (CH2CH2S),
110.91 (C-7), 118.97 (q, CF3, J=271.49 Hz), 121.63 (C-
5), 125.88 (C-6), 134.34 (C-4), 136.47 (C-7a), 139.54 (C-
3a), 140.75 (q, C-2, J=38.70 Hz) ppm; MS: m/z (% rel.
int.) 274 (M+, 100), 245 (20), 232 (75); HRMS: calcd for
C12H13F3N2S: 274.0751, found: 274.0767.
1-Methyl-5-(propylthio)-2-(trifluoromethyl)-1H- benzimi-
dazole (8). Eluted with hexane and recrystallized from
cyclohexane-CH2Cl2. Yield 7.98 g (93%) of white solid.
Mp 52.4–54.5 ꢁC. 1H NMR (300 MHz, CDCl3) d 1.01 (t,
3H, CH3CH2), 1.65 (m, 2H, CH3CH2CH2), 2.92 (t, 2H,
CH2CH2S), 3.94 (s, H, N-CH3), 7.36 (d, 1H, H-7,
J=8.7 Hz), 7.47 (dd, 1H, H-6, J=8.55, J=1.50 Hz),
7.87 (d, 1H, H-4, J=1.50 Hz) ppm; 13C NMR
General method of synthesis of propylsulfinyl derivatives
5a, 5b, 9
A stirred suspension of 4a, 4b, or 8 in CHCl3 was trea-
ted, dropwise, with a solution of m-CPBA in CHCl3 at
0–5 ꢁC. The mixture was stirred at 5 ꢁC for 30 min,
neutralized with 50% NaHCO3 solution, and the
organic layer was eliminated in vacuo. The crude pro-
duct was then purified.
(75.5 MHz, CDCl3)
d
13.30 (CH3CH2), 22.41
(CH3CH2CH2), 30.94 (N-CH3), 36.93 (CH2CH2S),
110.35 (C-7), 118.87 (q, CF3, J=271.42 Hz), 122.26 (C-
4), 128.31 (C-6), 132.09 (C-5), 134.60 (C-7a), 140.96 (q,
C-2, J=39.10 Hz), 141.21 (C-3a) ppm; MS: m/z (% rel.
int.) 274 (M+, 98), 245 (30), 232 (100); HRMS: calcd for
C12H13F3N2S: 274.0751, found: 274.0752.
5(6)-(Propylsulfinyl)-2-(trifluoromethyl)-1H-benzimida-
zole (5a). Following the general procedure described
above, 4a (3.5 g, 0.0134 mol) in 30 mL of CHCl3 and m-
CPBA (3.24 g, 0.0188 mol) in 20 mL of CHCl3 gave 5a
(3.2 g, 0.0116 mol, 86%) as a white solid, after recrys-
tallization from cyclohexane-toluene. Mp 123.2–
5(6)-Benzoyl-2-(trifluoromethyl)-1H-benzimidazole (12a).
Eluted with CHCl3 and recrystallized from EtOH. Yield
125.2 ꢁC. H NMR (300 MHz, CDCl3) d 0.93 (t, 3H,
1
6.53 g (72%) of white solid. Mp 55–58 ꢁC. H NMR
CH3CH2), 1.34–1.72 (m, 2H, CH3CH2CH2), 2.73–2.97
(m, 2H, CH2CH2SO), 7.62 (dd, 1H, H-6, J=8.40,
J=1.50 Hz), 7.89 (d, 1H, H-7, J=8.40 Hz), 8.01 (d, 1H,
H-4, J=0.90 Hz), 13.84 (bs, 1H, N-H) ppm; 13C NMR
1
(300 MHz, DMSO-d6) d 7.53–7.78 (m, 5H, H-20, H-30,
H-40, H-50, H-60), 7.83 (dd, 1H, H-6, J=8.40, J=1.20
Hz), 7.85 (d, 1H, H-7, J=8.40 Hz), 8.05 (d, 1H, H-4,
J=1.20 Hz), 10.40 (bs, 1H, N-H) ppm; 13C NMR
(75.5 MHz, DMSO-d6) d 113.52 (C-7), 114.66 (q, CF3,
J=270.96 Hz), 120.08 (C-4), 121.57 (C-6), 124.46 (C-20,
C-60), 125.55 (C-30, C-50), 128.43 (C-40), 128.85 (C-5, C-10),
133.42 (C-3a, C-7a), 138.34 (q, C-2, J=39.80 Hz),
196.91 (C¼O) ppm; MS: m/z (% rel. int.) 290 (M+,
100), 213 (98), 185 (50), 105 (70); HRMS: calcd for
C15H9F3N2O: 290.0666, found: 290.0690.
(75.5 MHz, CDCl3)
d
12.88 (CH3CH2), 15.18
(CH3CH2CH2), 57.71 (CH2CH2SO), 113.43 (C-4),
117.38 (C-7), 118.81 (q, CF3, J=271.42 Hz), 119.53 (C-
6), 138.20 (C-3a), 139.12 (C-7a), 140.04 (C-5), 141.76 (q,
C-2, J=39.40 Hz) ppm; MS: m/z (% rel. int.) 276 (M+,
100), 260 (30); HRMS: calcd for C11H11F3N2OS:
276.0544, found: 276.0563.
1-Methyl-6-(propylsulfinyl)-2-(trifluoromethyl)-1H-benzi-
midazole (5b). Following the general procedure descri-
bed above, 4b (5 g, 0.0182 mol) in 42 mL of CHCl3 and
m-CPBA (4.1 g, 0.0241 mol) in 30 mL of CHCl3 gave 5b
(4.8 g, 0.0165 mol, 90%) as a white solid, after recrys-
tallization from cyclohexane–petroleum ether. Mp 90.7–
91.8 ꢁC. 1H NMR (300 MHz, CDCl3) d 1.0 (t, 3H,
5-Benzoyl-1-methyl-2-(trifluoromethyl)-1H-benzimidazole
(12b). Eluted with CHCl3 and recrystallized from
cyclohexane. Yield 7.61 g (80%) of white solid. Mp
103.1–104.2 ꢁC. Mp 55–56.9 ꢁC. 1H NMR (300 MHz,
CDCl3) d 4.01 (s, 3H, N-CH3), 7.49–7.54 (m, 2H, H-30,
H-50), 7.60–7.66 (m, 3H, H-20, H-40, H-60), 7.81 (dd, 1H,