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DOI: 10.1055/s-0030-1260764
N-Aryl-2-nitrosoanilines as Intermediates in the Two-Step Synthesis of Substituted 1,2-Diarylbenzimidazoles from Simple Nitroarenes
Publication History
Publication Date:
26 May 2011 (online)

Abstract
N-Aryl-2-nitrosoanilines, easily available from reaction of nitroarenes with anilide anions, undergo base-promoted condensation reaction with substituted benzyl aryl sulfones, furnishing 1,2-diaryl-1H-benzimidazoles.
Key words
heterocycles - nitroso group - carbanions - condensation - sulfones - cyclization
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References and Notes
Procedure A
To
a solution of the nitrosoaniline 1 (0.5
mmol) and the sulfone (0.6 mmol) in a specified solvent (3 mL or
6 mL in the case of K2CO3 used as base) DBU
(0.3 mL), Et3N (0.3 mL), or K2CO3 (700
mg) was added, according to Table
[¹]
, and
the mixture was stirred at r.t. for the time specified in Table
[¹]
. In the case when K2CO3 was
used, it was then filtered off. The mixture was poured into 10% HCl
aq (ca. 50 mL) and extracted with EtOAc. The extract was washed
with H2O and brine and dried with Na2SO4.
After evaporation, the crude product mixture was subjected to column chromatography
(SiO2, hexane-EtOAc).
Procedure B
A
solution of nitrosoaniline 1b (163 mg,
0.614 mmol) and benzyl tolyl sulfone (184 mg, 0.75 mmol) in toluene
(3 mL) was vigorously stirred with 50% NaOH (1 mL) and
TBAB (30 mg) at r.t. for 1.5 h. The mixture was then diluted with H2O
(100 mL) and extracted with EtOAc. The extracts were washed with
H2O three times, dried with Na2SO4,
and evaporated. The mixture was subjected to column chromatography
(SiO2, hexane-EtOAc), and the crude 3m was recrystallized from EtOAc.
Analytical Data
for the Products 3a-m
6-Chloro-1-(4-ethoxyphenyl)-4-methoxy-2-(4-nitrophenyl)-1
H
-benzimidazole
(3a)
Yellow crystals, mp 211-212 ˚C. ¹H
NMR (400 MHz, CDCl3): δ = 1.37
(t, J = 7.0
Hz, 3 H), 4.03 (s, 3 H), 4.10 (q, J = 7.0
Hz, 2 H), 6.74 (d, J = 1.8
Hz, 1 H), 6.92 (d, J = 1.8 Hz,
1 H), 7.09-7.13 (m, 2 H), 7.38-7.43 (m, 2 H),
7.75-7.79 (m, 2 H), 8.21-8.25 (m, 2 H). ¹³C
NMR (100 MHz, CDCl3): δ = 14.6,
56.3, 63.5, 103.2, 105.4, 115.8, 123.6, 127.9, 128.7, 129.2, 130.0,
131.6, 135.6, 139.2, 147.6, 149.0, 151.8, 159.0. MS (EI): m/z (%) = 423
(95) [M+], 422 (100), 394
(43), 376 (9), 348 (13). Anal. Calcd for C22H18O4N3Cl: C,
62.3; H, 4.3; N, 9.9. Found: C, 62.3; H, 4.3; N, 9.8.
6-Chloro-2-(5-chloro-2-nitrophenyl)-1-(4-ethoxyphenyl)-4-methoxy-1
H
-benzimidazole
(3b)
Yellow solid, mp 145-148 ˚C. ¹H
NMR (400 MHz, DMSO-d
6): δ = 1.33
(t, J = 7.0
Hz, 3 H), 4.00 (s, 3 H), 4.04 (q, J = 7.0
Hz, 2 H), 6.84 (d, J = 1.8
Hz, 1 H), 6.93 (d, J = 1.8 Hz,
1 H), 6.99-7.04 (m, 2 H), 7.23-7.28 (m, 2 H),
7.83 (dd, J = 8.7,
2.3 Hz, 1 H), 7.89 (d, J = 2.3
Hz, 1 H), 8.09 (d, J = 8.7
Hz, 1 H). ¹³C NMR (100 MHz, DMSO-d
6): δ = 14.5, 56.3,
63.4, 103.02, 105.3, 115.5, 126.4, 126.5, 126.6, 128.2, 129.0, 131.3,
131.5, 132.7, 137.7, 138.2, 146.9, 147.1, 151.7, 158.7. MS (EI): m/z (%) = 459
(70), 457 (100) [M+], 428
(23), 409 (13), 289 (34), 261 (45). HRMS (EI): m/z calcd for
C22H17O4N3
³5Cl2 [M]+:
457.0596; found: 457.0611.
6-Chloro-2-(5-methoxy-4-methyl-2-nitrophenyl)-1-(4-ethoxyphenyl)-4-methoxy-1
H
-benzimidazole
(3c)
Creamy powder, mp 175-176 ˚C
(hexane-EtOAc). ¹H NMR (600 MHz, DMSO-d
6): δ = 1.32
(t, J = 7.0
Hz, 3 H), 2.23 (s, 3 H), 3.87 (s, 3 H), 4.00 (s, 3 H), 4.02 (q, J = 7.0 Hz,
2 H), 6.81 (d, J = 1.7
Hz, 1 H), 6.92 (d, J = 1.7
Hz, 1 H), 6.96-6.99 (m, 2 H), 7.20-7.24 (m, 2
H), 7.31 (s, 1 H), 7.94 (s, 1 H). ¹³C NMR
(125 MHz, CDCl3): δ = 14.7,
16.1, 56.1, 56.3, 63.7, 103.5, 104.9, 113.7, 115.2, 125.7, 127.1,
127.2, 128.0, 129.5, 129.9, 131.7, 137.9, 140.7, 149.4, 151.7, 158.9, 161.2.
MS (EI): m/z (%) = 467
(100) [M+], 438 (14), 289 (68),
178 (21). HRMS (EI): m/z calcd
for C24H22O5N3
³5Cl [M]+:
467.1248; found: 467.1256.
6-Chloro-2-(4-
tert
-butyl-2-nitrophenyl)-1-(4-ethoxyphenyl)-4-methoxy-1
H
-benzimidazole
(3d)
Yellow powder, mp 162-163 ˚C. ¹H
NMR (500 MHz, DMSO-d
6): δ = 1.18
(t, J = 7.1
Hz, 3 H), 1.31 (s, 9 H), 3.99 (s, 3 H), 4.03 (q, J = 7.1
Hz, 2 H), 6.81 (d, J = 1.8
Hz, 1 H), 6.91 (d, J = 1.8
Hz, 1 H), 6.99-7.03 (m, 2 H), 7.25-7.28 (m, 2
H), 7.60 (d, J = 8.1
Hz, 1 H), 7.81 (dd, J = 8.1,
1.9 Hz, 1 H), 7.98 (d, J = 1.9
Hz, 1 H). ¹³C NMR (100 MHz, DMSO-d
6): δ = 14.0,
30.5, 35.0, 56.2, 63.4, 103.0, 105.2, 115.4, 121.1, 122.0, 126.9,
128.2, 128.7, 130.3, 131.5, 132.5, 137.9, 148.1, 148.9, 151.5, 154.5,
158.6. MS (EI): m/z (%) = 479
(100) [M+], 450 (19), 289
(59) 260 (53). HRMS (EI): m/z calcd
for C26H26O4N3
³5Cl [M]+:
479.1612; found: 479.1606.
7-[6-Chloro-4-methoxy-1-(4-ethoxyphenyl)-1
H
-benzimidazol-2-yl]-8-nitroquinoline
(3e)
Pale yellow crystals, mp 127-130 ˚C
(hexane-EtOAc). ¹H NMR (500 MHz, DMSO-d
6): δ = 1.31
(t, J = 7.0
Hz, 3 H), 4.02 (q, J = 7.0
Hz, 2 H), 4.04 (s, 3 H), 6.88 (d, J = 1.7
Hz, 1 H), 6.95 (d, J = 1.7
Hz, 1 H), 7.02-7.05 (m, 2 H), 7.33-7.36 (m, 2
H), 7.52 (d, J = 8.6
Hz, 1 H), 7.80 (dd, J = 8.4,
4.1 Hz, 1 H), 8.15 (d, J = 8.6
Hz, 1 H), 8.55 (dd, J = 8.4,
1.5 Hz, 1 H), 9.09 (dd, J = 4.1,
1.5 Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d
6): δ = 14.9,
56.8, 63.9, 103.6, 106.1, 116.0, 123.0, 124.7, 127.3, 127.4, 128.7,
129.2, 130.0, 130.8, 132.1, 137.0, 138.6, 138.7, 146.2, 148.1, 152.2,
154.0, 159.3. MS (EI): m/z (%) = 474
(100) [M+], 429 (31), 289
(59), 261 (66), 155 (25). HRMS (EI): m/z calcd
for C25H19O4N4
³5Cl [M]+: 474.1095;
found: 474.1089.
2-(3,4-Dichlorophenyl)-6-methoxy-1-(4-methylphenyl)-1
H
-benzimidazole
(3f)
Yellow crystals, mp 173-177 ˚C
(hexane-EtOAc). ¹H NMR (400 MHz, DMSO-d
6): δ = 2.42
(s, 3 H), 3.73 (s, 3 H), 6.61 (d, J = 2.3
Hz, 1 H), 6.95 (dd, J = 8.8,
2.3 Hz, 1 H), 7.32-7.36 (m, 3 H), 7.39-7.46 (m,
2 H), 7.62 (d, J = 8.4
Hz, 1 H), 7.68 (d, J = 8.8
Hz, 1 H), 7.74 (d, J = 2.0
Hz, 1 H). ¹³C NMR (100 MHz, DMSO-d
6): δ = 20.8,
55.5, 93.3, 112.7, 120.2, 127.2, 128.5, 130.4, 130.5, 130.6, 130.7,
131.1, 131.9, 133.4, 136.7, 137.9, 138.7, 148.4, 157.0. MS (EI): m/z (%) = 384
(71), 382 (100) [M+], 367
(64), 159 (41). Anal. Calcd for C21H16ON2Cl2:
C, 65.8; H, 4.2; N, 7.3. Found: C, 65.6; H, 4.2; N, 7.3.
2-(5-Chloro-2-nitrophenyl)-6-methoxy-1-(4-methylphenyl)-1
H
-benzimidazole
(3g)
Yellow crystals, mp 155-158 ˚C
(hexane-EtOAc). ¹H NMR (400 MHz, DMSO-d
6): δ = 2.34
(s, 3 H), 3.75 (s, 3 H), 6.73 (d, J = 2.2
Hz, 1 H), 6.96 (dd, J = 8.8,
2.2 Hz, 1 H), 7.22-7.26 (m, 2 H), 7.28-7.34 (m,
2 H), 7.68 (d, J = 8.8
Hz, 1 H), 7.80 (dd, J = 8.8,
2.3 Hz, 1 H), 7.84 (d, J = 2.3
Hz, 1 H), 8.06 (d, J = 8.8
Hz, 1 H). ¹³C NMR (100 MHz, DMSO-d
6): δ = 20.6,
55.6, 93.3, 112.7, 120.4, 126.4, 126.6, 127.1, 130.4, 131.0, 132.1,
132.5, 136.6, 136.9, 137.9, 138.4, 146.2, 147.2, 157.1. MS (EI): m/z (%) = 393
(38) [M+], 348 (9), 225 (100),
182 (20). Anal. Calcd for C21H16N3O3Cl:
C, 64.0; H, 4.1; N, 10.7. Found: C, 63.8; H, 4.2; N, 10.6.
6-Methoxy-2-(5-methoxy-4-methyl-2-nitrophenyl)-1-(4-methylphenyl)-1
H
-benzimidazole
(3h)
Yellow crystals, mp 200-201 ˚C
(EtOH). ¹H NMR (500 MHz, CDCl3): δ = 2.26
(s, 3 H), 2.37 (s, 3 H), 3.80 (s, 3 H), 3.91 (s, 3 H), 6.73 (d, J = 2.3 Hz,
1 H), 6.99 (dd, J = 8.8,
2.3 Hz, 1 H), 7.04-7.08 (m, 3 H), 7.17 (m, 2 H), 7.76 (d, J = 8.8 Hz,
1 H), 7.80 (d, J = 0.8
Hz, 1 H). ¹³C NMR (125 MHz, CDCl3): δ = 16.1,
21.2, 55.9, 56.2, 93.8, 112.5, 113.5, 120.5, 126.0, 126.5, 127.1,
129.4, 130.2, 132.6, 136.9, 137.1, 138.5, 140.8, 148.9, 157.4, 161.2.
MS (EI): m/z (%) = 403 (50) [M+],
361 (16), 225 (100), 182 (15). Anal. Calcd for C23H21N3O4:
C, 68.5; H, 5.2; N, 10.4. Found: C, 68.4; H, 5.2; N, 10.4.
2-(4-
tert
-Butyl-2-nitrophenyl)-6-methoxy-1-(4-methylphenyl)-1
H
-benzimidazole
(3i)
Yellow crystals, mp 184-188 ˚C
(hexane-EtOAc). ¹H NMR (400 MHz, DMSO-d
6): δ = 1.31
(s, 9 H), 2.34 (s, 3 H), 3.75 (s, 3 H), 6.70 (d, J = 2.3
Hz, 1 H), 6.94 (dd, J = 8.8,
2.3 Hz, 1 H), 7.24-7.33 (m, 4 H), 7.54 (d, J = 8.1 Hz,
1 H), 7.65 (d, J = 8.8
Hz, 1 H), 7.77 (dd, J = 8.1,
1.9 Hz, 1 H), 7.96 (d, J = 1.9
Hz, 1 H). ¹³C NMR (100 MHz, DMSO-d
6): δ = 20.7, 30.5,
35.0, 55.6, 93.4, 112.4, 120.2, 121.0, 122.5, 126.6, 130.1, 130.4,
132.3, 132.5, 136.6, 137.0, 138.2, 147.4, 149.1, 154.2, 156.8. MS
(EI): m/z (%) = 415
(53) [M+], 370 (17), 225 (100),
182 (13). Anal. Calcd for C25H25N3O4:
C, 72.3; H, 6.1; N, 10.1. Found: C, 72.1; H, 6.2; N, 9.9.
6-Chloro-1-(4-chlorophenyl)-2-(3,4-dichlorophenyl)-1
H
-benzimidazole
(3j)
Yellow solid, mp 176-178 ˚C. ¹H
NMR (400 MHz, DMSO-d
6): δ = 7.29
(d, J = 2.2
Hz, 1 H), 7.37 (dd, J = 8.4,
2.2 Hz, 1 H), 7.38 (dd, J = 8.8,
2.2 Hz, 1 H), 7.54-7.58 (m, 2 H), 7.66-7.70 (m,
3 H), 7.79 (d, J = 2.2
Hz, 1 H), 7.84 (d, J = 8.8
Hz, 1 H). ¹³C NMR (100 MHz, DMSO-d
6): δ = 111.0,
121.5, 124.0, 128.9, 129.5, 129.9, 130.2, 130.7, 131.2, 131.5, 131.8,
133.2, 134.4, 134.8, 138.1, 141.6, 151.0. MS (EI):
m/z (%) = 408
(100), 407 (89), 406 (76) [M+],
372 (20), 370 (20), 336 (7). Anal. Calcd for C19H10N2Cl4:
C, 55.9; H, 2.5; N, 6.9. Found: C, 55.9; H, 2.7; N, 6.8.
6-Chloro-1-(4-chlorophenyl)-2-(5-chloro-2-nitrophenyl)-1
H
-benzimidazole
(3k)
Pale yellow crystals, mp 148-149 ˚C
(hexane-EtOAc). ¹H NMR (400 MHz, CDCl3): δ = 7.15-7.18
(m, 2 H), 7.27 (d, J = 1.9
Hz, 1 H), 7.35 (dd, J = 8.6,
1.9 Hz, 1 H), 7.40-7.43 (m, 2 H), 7.58 (dd, J = 2.3, 8.8
Hz, 1 H), 7.68 (d, J = 2.3
Hz, 1 H), 8.62 (d, J = 8.6
Hz, 1 H), 7.99 (d, J = 8.8
Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 110.5,
121.5, 124.3, 126.2, 127.2, 128.1, 130.3, 130.4, 131.1, 132.9, 133.0,
135.3, 136.6, 140.1, 141.5, 146.7, 148.4. MS (EI): m/z (%) = 419 (24),
417 (25) [M+], 372 (27), 249
(100), 214 (22), 169 (16), 138 (18), 111 (28). HRMS (EI): m/z calcd for C19H10O2N3
³5Cl3 [M]+:
416.9839; found: 416.9842.
6-Chloro-1-(4-chlorophenyl)-2-(2-nitrophenyl)-1
H
-benzimidazole
(3l)
Yellow crystals, mp 274-275 ˚C
(MeOH). ¹H NMR (400 MHz, CDCl3): δ = 7.23
(d, J = 2.0
Hz, 1 H), 7.25-7.29 (m, 2 H), 7.36 (dd, J = 8.8,
2.0 Hz, 1 H), 7.53-7.58 (m, 2 H), 7.72-7.76 (m,
2 H), 7.81 (d, J = 8.8
Hz, 1 H), 8.18-8.22 (m, 2 H). ¹³C
NMR (100 MHz, CDCl3): δ = 110.6,
121.3, 123.7, 124.6, 128.4, 130.1, 130.5, 130.8, 134.3, 135.2, 135.7, 137.7,
141.4, 148.2, 150.3. MS (EI): m/z (%) = 383
(100) [M+], 336 (39), 302
(15), 266 (12). HRMS (EI): m/z calcd
for C19H11O2N3
³5Cl2 [M]+:
383.0228; found: 383.0216.
6-Methoxy-1-(4-methylphenyl)-2-phenyl-1
H
-benzimidazole
(3m)
Solid, mp 166-167 ˚C (EtOAc). ¹H
NMR (500 MHz, DMSO-d
6): δ = 2.40
(s, 3 H), 3.72 (s, 3 H), 6.61 (d, J = 2.4 Hz,
1 H), 6.93 (dd, J = 8.8,
2.4 Hz, 1 H), 7.28-7.39 (m, 7 H), 7.47-7.50 (m,
2 H), 7.67 (d, J = 8.8
Hz, 1 H). ¹³C NMR (125 MHz, DMSO-d
6): δ = 20.7,
55.5, 93.4, 112.1, 119.9, 127.2, 128.3, 128.8, 129.1, 130.1,130.5,
133.9, 136.9, 137.8, 138.3, 150.9, 156.6. MS (EI): m/z (%) = 314
(100) [M+], 299 (50). Anal.
Calcd for C21H18ON2: C, 80.2; H,
5.8; N, 8.9. Found: C, 79.9; H, 5.7; N, 8.9.