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Synlett 2011(10): 1439-1443  
DOI: 10.1055/s-0030-1260764
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

N-Aryl-2-nitrosoanilines as Intermediates in the Two-Step Synthesis of Substituted 1,2-Diarylbenzimidazoles from Simple Nitroarenes

Zbigniew Wróbel*a, Karolina Stachowskaa, Krzysztof Grudzieńb, Andrzej Kwasta
a Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44, 01-224 Warszawa 42, POB 58, Poland
Fax: +48(22)6326681; e-Mail: wrobel@icho.edu.pl;
b Faculty of Chemistry, University of Warsaw, ul. Pasteura 1, 02-093 Warszawa, Poland
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Received 17 January 2011
Publikationsdatum:
26. Mai 2011 (online)

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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

    References and Notes

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14

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).

15

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.

16

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.