PDF icon PDF herunterladen
Synlett 2012; 23(9): 1315-1320
DOI: 10.1055/s-0031-1291044
letter
© Georg Thieme Verlag Stuttgart · New York

Expedient Synthesis of 1-Hydroxy-4- and 1-Hydroxy-6-nitroindoles

Robert Bujok
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/51, P.O. Box 58, 01-224 Warszawa 42, Poland, Fax: +48(22)6326681   eMail: krzysztof.wojciechowski@icho.edu.pl
,
Zbigniew Wróbel
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/51, P.O. Box 58, 01-224 Warszawa 42, Poland, Fax: +48(22)6326681   eMail: krzysztof.wojciechowski@icho.edu.pl
,
Krzysztof Wojciechowski*
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/51, P.O. Box 58, 01-224 Warszawa 42, Poland, Fax: +48(22)6326681   eMail: krzysztof.wojciechowski@icho.edu.pl
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 14. Februar 2012

Accepted after revision: 26. März 2012

Publikationsdatum:
14. Mai 2012 (online)

   Lizenzen und Reprints Alle Artikel dieser Rubrik


Preview

Abstract

Reaction of α-chloroalkyl ketones with 1,3-dinitrobenzenes provides 2,4-dinitrobenzyl ketones which when reduced with tin(II) chloride form 6-nitro derivatives of 1-hydroxyindoles. An alternative approach is the condensation of 2,4- and 2,6-dinitrotoluenes with diethyl oxalate or ethyl trifluoroacetate provides dinitrobenzyl ketones which leads after reduction with tin(II) chloride to nitro derivatives of 1-hydroxyindol-2-carboxylates or 1-hydroxy-2-(trifluoromethyl)indoles, respectively.

Key words

indoles - acylation - reduction - nucleophilic aromatic substitution - tin - ketones
 

  • References and Notes

    • 2a Granchi C, Roy S, Del FiandraC, Tuccinardi T, Lanza M, Betti L, Giannaccini G, Lucacchini A, Martinelli A, Macchia M, Minutolo F. Med. Chem. Commun. 2011; 2: 638
      CrossrefSuche in Google Scholar
    • 2b Granchi C, Roy S, Giacomelli C, Macchia M, Tuccinardi T, Martinelli A, Lanza M, Betti L, Giannaccini G, Lucacchini A, Funel N, Leon LG, Giovannetti E, Peters GJ, Palchaudhuri R, Calvaresi EC, Hergenrother PJ, Minutolo F. J. Med. Chem. 2011; 54: 1599
      CrossrefSuche in Google Scholar
    • 2c Granchi C, Roy S, Mottinelli M, Nardini E, Campinoti F, Tuccinardi T, Lanza M, Betti L, Giannaccini G, Lucacchini A, Martinelli A, Macchia M, Minutolo F. Bioorg. Med. Chem. Lett. 2011; 21: 7331
      CrossrefSuche in Google Scholar
  • 4 Acheson RM, Littlewood DM, Rosenberg HE. J. Chem. Soc., Chem. Comm. 1974; 671
  • 5 Somei M, Ohnishi H, Shoken Y. Chem. Pharm. Bull. 1986; 34: 677
    CrossrefSuche in Google Scholar
  • 6 Preston PN, Tennant G. Chem. Rev. 1972; 72: 627
    CrossrefSuche in Google Scholar
  • 8 Camara HD, Attar K, Benchidmi M, Essassi EM, Garriques B. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 2004; 43: 660
    Suche in Google Scholar
  • 9 Wong A, Kuethe JT, Davies IW. J. Org. Chem. 2003; 68: 9865
    CrossrefSuche in Google Scholar
  • 12 Wróbel Z, Mąkosza M. Pol. J. Chem. 1992; 66: 2005
    Suche in Google Scholar
  • 13 General Procedure for the Synthesis of Dinitrobenzyl Ketones 4a–f To a stirred solution of 1,3-dinitrobenzene (10 mmol) and α-chloromethyl ketone (2, 10 mmol) in DMF (25 mL) cooled to –20 °C was added DBU (5.32 g, 5.2 mL, 35 mmol). The stirring was continued for 40 min allowing the reaction mixture to reach r.t. Then the reaction mixture was stirred for additional 20 min and poured into diluted HCl (100 mL). The precipitate was filtered, diluted with EtOAc (50 mL), washed with brine, and dried with Na2SO4. After evaporation of the solvent the residue was chromatographed on silica gel with EtOAc–hexane (2:1). The following compounds were obtained. 1-(2,4-Dinitrophenyl)-propan-2-one (3a) Pale yellow crystals, mp 65–67 °C (lit. 12 66–67 °C). 1-(2,4-Dinitrophenyl)-3,3-dimethylbutan-2-one (3b) Orange crystals, mp 60–62 °C. 1H NMR (500 MHz, CDCl3): δ = 1.20 (s, 9 H), 4.24 (s, 2 H), 7.47 (d, J = 8.3 Hz, 1 H), 8.40 (dd, J = 8.3, 2.3 Hz, 1 H), 8.94 (d, J = 2.3 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 26.59, 42.70, 44.45, 120.54, 127.09, 128.86, 134.69, 137.92, 147.14, 149.25, 209.54. ESI-MS: m/z = 555 [2M + Na+], 289 [M + Na+]. ESI-HRMS: m/z calcd for C12H14N2O5Na: 289.0795; found: 289.0786. 1-(2,4-Dinitrophenyl)-2-phenylethanone (3c) Pale yellow crystals, mp 133–135 °C (lit.12 136–137 °C). 1H NMR (500 MHz, CDCl3): δ = 4.87 (s, 2 H), 7.51–7.55 (m, 2 H), 7.59 (d, J = 8.5 Hz, 1 H), 7.63–7.68 (m, 2 H), 8.01–8.04 (m, 2 H), 8.46 (dd, J = 8.5, 2.2 Hz, 1 H), 8.98 (d, J = 2.2 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 44.14, 120.68, 127.32, 128.27, 128.92, 134.01, 134.93, 135.87, 137.56, 147.37, 149.23, 193.86. ESI-MS: m/z = 309 [M + Na+]. ESI-HRMS: m/z calcd for C14H10N2O5Na: 309.0482; found: 309.0497. 1-(4-Chlorophenyl)-2-(2,4-dinitrophenyl)-ethanone (3d) Yellow crystals, mp 145–147 °C. 1H NMR (500 MHz, CDCl3): δ = 4.83 (s, 2 H), 7.50–7.53 (m, 2 H), 7.59 (d, J = 8.4 Hz, 1 H), 7.95–7.99 (m, 2 H), 8.47 (dd, J = 8.4, 2.4 Hz, 1 H), 9.00 (d, J = 2.4 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 44.09, 120.75, 127.42, 129.28, 129.66, 134.18, 134.94, 137.17, 140.60, 147.47, 149.09, 192.75. ESI-HRMS: m/z calcd for C14H9N2O5ClNa: 343.0092; found: 343.0106. 1-(2,4-Dinitrophenyl)-2-(4-methoxyphenyl)ethanone (3e) Yellow crystals, mp 102–103 °C (lit.10b 102–105 °C). 1H NMR (500 MHz, CDCl3): δ = 3.90 (s, 3 H), 4.82 (s, 2 H), 6.97–7.01 (m, 2 H), 7.58 (d, J = 8.4 Hz, 1 H), 7.98–8.02 (m, 2 H), 8.43 (dd, J = 8.4, 2.3 Hz, 1 H), 8.97 (d, J = 2.3 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 43.70, 55.58, 114.06, 120.57, 127.19, 128.86, 130.62, 134.88, 137.86, 147.25, 149.30, 164.19, 192.21. MS (EI, 70 eV): m/z (%) = 316 (2) [M+], 152 (1), 135 (100), 107 (4), 92 (7), 77 (10). ESI-HRMS: m/z calcd for C15H12N2O6Na: 339.0588; found: 339.0590
  • 14 1-Hydroxy-nitroindoles from Dinitrobenzyl Ketones – General Procedure To dinitrobenzyl ketone (2 mmol) dissolved in EtOAc (10 mL) and EtOH (1 mL) SnCl2 (1.44 g, 7.6 mmol) was added in one portion. The reaction mixture was stirred overnight at r.t. The reaction mixture was then evaporated, and the residue was subjected to column chromatography on silica gel. The product was eluted with EtOAc–hexane (4:1). The following compounds were obtained. 1-Hydroxy-2-methyl-6-nitroindole (4a) Orange crystals, mp 153–155 °C. 1H NMR [500 MHz, (CD3)2CO]: δ = 2.51 (d, J = 1.0 Hz, 3 H), 6.32 (q, J = 1.0 Hz, 1 H), 7.58 (d, J = 8.8 Hz, 1 H), 7.89 (dd, J = 8.8, 2.2 Hz‚ 1 H), 8.28 (d, J = 2.2 Hz, 1 H), 10.49 (br s, 1 H). 13C NMR [125 MHz, (CD3)2CO]: δ = 11.34, 97.21, 105.24, 115.22, 120.36, 129.22, 133.19, 142.35, 142.98. IR (KBr): ν = 3261, 1609, 1583, 1505, 1458, 1392, 1365, 1326, 1276, 1220, 1134, 865, 762 cm–1. MS (EI, 70 eV): m/z (%) = 192 (100) [M+], 191 (10), 176 (22), 162 (7), 146 (32), 145 (15)130 (12), 129 (23), 128 (16), 117 (23), 103 (16), 102 (17). HRMS (EI): m/z calcd for C9H8N2O3: 192.0535; found: 192.0541. 2-tert-Butyl-1-hydroxy-6-nitroindole (4b) Orange crystals, mp 147–149 °C. 1H NMR [500 MHz, (CD3)2CO]: δ = 1.51 (s, 9 H), 6.32 (d, J = 0.9 Hz, 1 H), 7.61 (dd, J = 8.6, 0.6 Hz, 1 H), 7.89 (dd, J = 8.7, 2.1 Hz, 1 H), 8.26 (br d, J = 2.2 Hz, 1 H), 10.64 (br s, 1 H). 13C NMR [125 MHz, (CD3)2CO]: δ = 29.23, 33.33, 95.00, 96.62, 105.29, 115.19, 120.78, 128.44, 134.52, 143.20, 153.52. MS (EI, 70 eV): m/z (%) = 234 (71) [M+], 219 (100), 203 (12), 202 (13), 201 (17), 173 (13), 172 (12), 156 (13), 155 (15). HRMS (EI): m/z calcd for C12H14N2O3: 234.1004, found: 234.0997. 1-Hydroxy-2-phenyl-6-nitroindole (4c) Red-orange crystals, mp 158–160 °C. 1H NMR [500 MHz, (CD3)2CO]: δ = 6.84 (s, 1 H), 7.45–7.50 (m, 1 H), 7.51–7.56 (m, 2 H), 7.74 (d, J = 8.7 Hz, 1 H), 7.95–7.99 (m, 3 H), 8.41 (d, J = 2.1 Hz, 1 H), 10.72 (br s, 1 H). 13C NMR [125 MHz, (CD3)2CO]: δ = 97.52, 105.31, 115.06, 120.57, 128.11, 128.36, 128.72, 128.94, 129.94, 134.13, 143.03, 143.08. IR (KBr): ν = 3247, 1607, 1501, 1478, 1467, 1316, 1273, 1081, 818, 763 cm–1. MS (EI, 70 eV): m/z (%) = 254 (100) [M+], 238 (25), 225 (11), 224 (10), 208 (24), 207 (17), 191 (23), 190 (38), 180 (17), 179 (50), 165 10), 164 (10), 163 (11), 152 (10). HRMS (EI): m/z calcd for C14H10N2O3: 254.0691; found: 254.0695. 2-(4-Chlorophenyl)-1-hydroxy-6-nitroindole (4d) Orange crystals, mp 201–203 °C. 1H NMR [500 MHz, (CD3)2CO]: δ = 6.86 (d, J = 1.0 Hz, 1 H), 7.54–7.58 (m, 2 H), 7.73 (d, J = 8.7 Hz, 1 H), 7.96 (dd, J = 8.7, 2.1 Hz, 1 H), 7.97–8.00 (m, 2 H), 8.38 (br d, 2.1 Hz, 1 H), 10.81 (br s, 1 H). 13C NMR [125 MHz, (CD3)2CO]: δ = 98.70, 106.24, 116.01, 121.61, 128.81, 129.58, 129.73, 130.72, 135.06, 135.26, 142.48, 144.09. IR (KBr): ν = 3278, 1608, 1536, 1506, 1479, 1336, 1286, 1279, 1084, 813, 773, 761, 726 cm–1. MS (EI, 70 eV): m/z (%) = 280 (57) [M+], 270 (100), 258 (20), 242 (35), 213 (36), 206 (15), 191 (45), 190 (60), 178 (22). HRMS (EI): m/z calcd for C14H9 35ClN2O3: 288.0302; found: 288.0299. 1-Hydroxy-2-(4-methoxyphenyl)-6-nitroindole (4e) Red-orange crystals, mp 183–185 °C. 1H NMR [500 MHz, (CD3)2CO]: δ = 3.88 (s, 3 H), 6.74 (d, J = 1.0 Hz, 1 H), 7.07–7.11 (m, 2 H), 7.69 (d, J = 8.7 Hz, 1 H), 7.90–7.94 (m, 2 H), 7.96 (dd, J = 8.5, 2.0 Hz, 1 H), 8.37 (br d, J = 2.0 Hz, 1H), 10.70 (s, 1 H). 13C NMR [125 MHz, (CD3)2CO]: δ = 54.84, 96.44, 105.10, 114.17, 115.04, 120.11, 122.26, 128.31, 129.76, 133.95, 142.62, 143.20, 150.50. MS (EI, 70 eV): m/z (%) = 284 (15) [M+], 268 (100), 254 (14), 238 (29), 223 (13), 222 (44), 209 (13), 208 (9), 207 (20), 206 (10), 191 (9), 190 (7). HRMS (EI): m/z calcd for C15H12N2O4: 284.0797; found: 284.0805. Ethyl 1-Hydroxy-6-nitroindole-2-carboxylate (4f) Yellow crystals, mp 160–161 °C. 1H NMR [500 MHz, (CD3)2CO]: δ = 1.40 (t, J = 7.0 Hz, 3 H), 4.41 (q, J = 7.0 Hz, 2 H), 7.22 (br s, 1 H), 7.90 (d, J = 8.8 Hz, 1 H), 7.98 (dd, J = 8.8, 1.9 Hz, 1 H), 8.43 (br s, 1 H), 10.92 (br s, 1 H). 13C NMR [125 MHz, (CD3)2CO]: δ = 13.61, 61.04, 105.08, 106.29, 115.24, 123.20, 125.60, 131.12, 134.52, 145.45, 159.29. IR (KBr): ν = 3077, 1687, 1620, 1589, 1525, 1505, 1466, 1407, 1337, 1286, 1258, 1218, 1055, 1010, 826, 752, 726 cm–1. MS (EI, 70 eV): m/z (%) = 250 (33) [M+], 234 (8), 222 (6), 205 (14), 204 (100), 188 (10), 158 (9). HRMS (EI): m/z calcd for C11H10N2O5: 250.0590; found: 250.0596. 1-Hydroxy-6-nitro-2-(trifluoromethyl)indole (4g) Yellow crystals, mp 113–115 °C. 1H NMR [500 MHz, (CD3)2CO]: δ = 7.12 (dq, J = 1.2, 1.0 Hz, 1 H), 7.95 (d, J = 8.8 Hz, 1 H), 8.04 (dd, J = 8.8, 2.1 Hz, 1 H), 8.45 (br d, J = 2.1 Hz, 1 H), 11.39 (s, 1 H). 13C NMR [125 MHz, (CD3)2CO]: δ = 101.16 (q, J = 3.4 Hz), 106.79, 116.41, 120.96 (q, J = 268.4 Hz), 124.10, 126.48, 130.06 (q, J = 38.9 Hz), 134.87, 146.78. 19F NMR [470 MHz, (CD3)2CO]: δ = –61.83 (d, J = 1.2 Hz). IR (KBr): ν = 3245, 1559, 1511, 1338, 1290, 1244, 1173, 1148, 1132, 1040, 827, 729 cm–1. MS (EI, 70 eV): m/z (%) = 246 (100) [M+], 245 (23), 230 (60), 227 (13), 226 (41), 200 (32), 199 (12), 184 (42), 183 (35), 164 (12), 163 (17), 157 (10), 152 (20), 144 (15). HRMS (EI): m/z calcd for C9H5F3N2O3: 246.0252; found: 246.0246. Ethyl 1-Hydroxy-4-nitroindole-2-carboxylate (4h) Yellow crystals, mp 108–110 °C. 1H NMR [500 MHz, (CD3)2CO]: δ = 1.41 (t, J = 7.4 Hz, 3 H), 4.43 (q, J = 7.4 Hz, 2 H), 7.58 (dd, J = 8.2, 7.8 Hz, 1 H), 8.03 (br d, J = 8.2 Hz, 1 H), 8.19 (br d, J = 7.8 Hz, 1 H), 10.89 (br s, 1 H). 13C NMR [125 MHz, (CD3)2CO]: δ = 13.62, 61.07, 103.83, 114.73, 117.11, 118.71, 124.14, 129.35, 137.49, 141.04, 159.40. IR (KBr): ν = 3259, 1706, 1529, 1334, 1289, 1245, 1147, 1025, 751, 733 cm–1. MS (EI, 70 eV): m/z (%) = 250 (26) [M+], 234 (24), 205 (14), 204 (100), 188 (26), 158 (10), 142 (11), 114 (27), 102 (14). HRMS (EI): m/z calcd for C11H10N2O5: 250.0590; found: 250.0587. 1-Hydroxy-4-nitro-2-(trifluoromethyl)indole (4i) Yellow crystals, mp 159–161 °C. 1H NMR [500 MHz, (CD3)2CO]: δ = 7.46 (br s, 1 H), 7.63 (dd, J = 8.0, 8.0 Hz, 1 H), 8.07 (br d, J = 8.0 Hz, 1 H), 8.23 (br d, J = 8.0 Hz, 1 H), 11.37 (br s, 1 H). 13C NMR [125 MHz, (CD3)2CO]): δ = 99.09 (q, J = 4.0 Hz), 114.70, 116.95, 118.80, 120.21 (q, J = 268.0 Hz), 124.31, 127.70 (q, J = 38.4 Hz), 136.97, 141.12. 19F NMR [470 MHz, (CD3)2SO]: δ = –61.22 s). IR (KBr): ν = 3216, 1556, 1513, 1331, 1289, 1234, 1145, 799, 737 cm–1. MS (EI, 70 eV): m/z (%) = 246 (100) [M+], 245 (31), 230 (63)227 (17), 226 (43), 200 (40), 199 (30), 184 (51), 183 (11), 172 (13), 164 (15), 163 (23), 152 (22), 144 (18), 133 (12), 130 (14), 114 (22), 102 (44). HRMS (EI): m/z calcd for C9H5F3N2O3: 246.0252; found: 246.0256
  • 15 Noland WE, Baude FJ. Org. Synth. 1963; 43: 40 ; Org. Synth., Coll. Vol. V 1975, 567
    Suche in Google Scholar
    • 16a Bouchon A, Diedrichs N, Hermann A, Lustig K, Meier H, Pernerstorfer J, Reissmüller E, Muneto M, Fujishima H, Tajimi M, Yamamoto N. US 7683076, 2010
    • 16b Uchida H, Ogawa S, Makabe M, Maeda Y. EP 2128157, 2009
  • 17 Reaction of Dinitrotoluenes with Diethyl Oxalate – Synthesis of Ethyl 3-(2,4-Dinitrophenyl)-2-hydroxyacrylate (3f′) – Typical Procedure 2,4-Dinitrotoluene (5, 6.1 g, 33.5 mmol) in DMF (25 mL) was added dropwise to a cooled solution (–22 °C) of diethyl oxalate (23.7 g, 162 mmol) and DBU (12.2 g, 88 mmol) in DMF (100 mL). The reaction mixture was kept at –15 °C for 3 d and then poured into H2O (150 mL) and acidified with diluted HCl. The product was extracted with EtOAc (3 × 100 mL), washed with H2O, and dried with Na2SO4. After evaporation of the solvent the product was purified chromatographically on silica gel with hexane–EtOAc (4:1, to remove remaining diethyl oxalate – then 2:1); yield 7.25 g (78%); orange solid, mp 78–83 °C. 1H NMR (500 MHz, CDCl3): δ = 1.43 (t, J = 7.1 Hz, 3 H), 4.44 (q, J = 7.1 Hz, 2 H), 6.96 (s, 1 H), 7.13 (d, J = 1.3 Hz, 1 H), 8.42 (dd, J = 8.8, 2.3 Hz, 1 H), 8.52 (d, J = 8.8 Hz, 1 H), 9.02 (d, J = 2.3, 1 H). 13C NMR (125 MHz, (CDCl3): δ = 14.09, 63.85, 101.10, 120.09, 126.63, 132.68, 134.56, 144.18, 145.84, 147.95, 164.87. IR (KBr): ν = 3410, 3090, 1712, 1660, 1651, 1600, 1592, 1535, 1413, 1351, 1331, 1261, 1012, 864, 836, 773 cm–1. ESI-HRMS: m/z calcd for C11H10N2O7Na: 305.0380; found: 305.0387. Compound 3h was obtained analogously from 2,6-dinitrotoluene. Ethyl 2,6-Dinitrophenyl-glyoxalate (3h) Yellow semi-solid; yield 85%. 1H NMR (500 MHz, CDCl3): δ = 1.42 (t, J = 7.1 Hz, 3 H), 4.41 (q, J = 7.1 Hz, 2 H), 4.72 (s, 2 H), 7.71 (t, J = 8.2 Hz, 1 H), 8.25 (d, J = 8.2 Hz, 2 H).). 13C NMR (125 MHz, (CDCl3): δ = 13.95, 38.97, 63.25, 124.14, 129.10, 129.41, 150.96, 159.60, 187.10
  • 18 For a review on (trifluoromethyl)indoles, see: Muzalevskiy VM, Shastin AV, Balenkova ES, Haufe G, Nenajdenko VG. Synthesis 2009; 3905
    Thieme Connect
  • 19 Reaction of 2,4-Dinitrotoluene with Ethyl Trifluoroacetate – Synthesis of 1,1,1-Trifluoro-3-(2,4-dinitrophenyl)propan-2-one (3g) – Typical Procedure 2,4-Dinitrotoluene (5, 1.20 g, 6.6 mmol) in DMF (5 mL) was added dropwise to a cooled solution (–22 °C) of ethyl trifluoroacetate (6.55 g, 46 mmol) and DBU (2.54 g, 16.7 mmol) in DMF (15 mL). The reaction mixture was kept at –15 °C for 3 h and then poured into H2O (100 mL) and acidified with diluted HCl. The product was extracted with EtOAc (3 × 20 mL), washed with H2O, and dried with Na2SO4. After evaporation of the solvent the product was purified chromatographically on silica gel with hexane–EtOAc (2:1); yield 1.74 g (95%); yellow oil. 1H NMR (600 MHz, CDCl3): δ = 4.58 (s, 3 H), 7.61 (d, J = 8.2 Hz, 1 H), 8.53 (dd, J = 8.2, 2.3 Hz, 1 H), 9.07 (d, J = 2.3 Hz, 1 H); for hydrate 3g′: δ = 3.59 (s, 2 H), 7.80 (d, J = 8.6 Hz, 1 H), 8.44 (dd, J = 8.6, 2.4 Hz, 1 H), 8.77 (d, J = 2.4 Hz, 1 H). 19F NMR (470 MHz, CDCl3): δ (hydrate 3g′) = –78.50, –86.30. ESI-HRMS: m/z calcd for C9H4N2O5F3: 277.0067; found: 277.0064. 1,1,1-Trifluoro-3-(2,6-dinitrophenyl)propan-2-one (3i) and its hydrate 3i′ were obtained analogously from 2,6-dinitrotoluene and ethyl trifluoroacetate. 1,1,1-Trifluoro-3-(2,6-dinitrophenyl)propan-2-one (3i) and Hydrate 3i′ Yellow oil. For 3i: 1H NMR (500 MHz, CDCl3): δ = 4.61 (s, 2 H), 7.78 (t, J = 8.3 Hz, 1 H), 8.33 (d, J = 8.3 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 36.90, 115.42 (q, J = 292.5 Hz), 122.00, 129.51, 130.12, 150.84, 185.24 (q, J = 37.2 Hz). 19F NMR (470 MHz, CDCl3): δ = –78.27. MS (FD): m/z = 278 [M+]
  • 21 Korda A, Wróbel Z. Synlett 2003; 1465
    Thieme Connect
  • 22 GC analysis of the reaction mixture revealed the presence of a peak that matched the peak of phenylglyoxal standard
  • 23 Dehydroxylation of 1-Hydroxyindoles – General Procedure To a solution of 1-hydroxynitroindole (1 mmol) and α-bromoacetophenone (1 mmol) in MeOH (5 mL) Et3N (0.23 g, 2.3 mmol) was added in one portion at r.t. The reaction mixture was stirred for 3 h (TLC control). Then the reaction mixture was evaporated under vacuum, and the residue was chromatographed on silica gel with EtOAc–hexane (2:1). The following compounds were obtained. 2-Methyl-6-nitroindole (8a) Yellow crystals, mp 116–118 °C (lit. 24 118–119 °C). 1H NMR (500 MHz, CDCl3): δ = 2.52 (s, 3 H), 6.34 (s, 1 H), 7.51 (d, J = 8.6 Hz, 1 H), 7.98 (dd, J = 8.6, 1.8 Hz, 1 H) 8.26 (d, J = 1.8 Hz, 1 H), 8.45 (br s, 1 H). 13C NMR (125 MHz, CDCl3): δ = 13.99, 101.77, 107.22, 115.47, 119.13, 134.31, 134.45, 142.14, 142.22. MS (EI, 70 eV): m/z (%) = 176 (100) [M+], 146 (35), 130 (58), 118 (13), 103 (44). HRMS (EI): m/z calcd for C9H8N2O2: 176.0586; found: 176.0589. 2-tert-Butyl-6-nitroindole (8b) Yellow crystals; mp 125–127 °C. 1H NMR [500 MHz, (CD3)2SO]: δ = 1.39 (s, 9 H), 6.40 (dd, J = 2.0, 0.8 Hz, 1 H), 7.59 (d, J = 8.7 Hz, 1 H), 7.87 (dd, J = 8.7, 2.0 Hz, 1 H), 8.23 (br d, J = 2.0 Hz, 1 H), 11.71 (s, 1 H). 13C NMR [125 MHz, (CD3)2SO]: δ = 29.67, 32.16, 97.47, 107.24, 114.13, 119.29, 133.20, 134.53, 141.03, 156.61. MS (EI, 70 eV): m/z (%) = 218 (48) [M+], 203 (100), 173 94), 158 (12), 157 (47), 142 (5), 130 (5), 129 (4), 128 (5). HRMS (EI): m/z calcd for C12H14N2O2: 218.1055; found: 218.1059. 6-Nitro-2-phenylindole (8c) Orange crystals, mp 213–215 °C (lit. 24 214–216 °C). 1H NMR [500 MHz, (CD3)2SO]: δ = 7.42–7.47 (m, 1 H), 7.52–7.57 (m, 2 H), 7.72 (d, J = 8.7 Hz, 1 H), 7.92 (dd, J = 8.7, 2.2 Hz, 1 H), 7.93–7.97 (m, 2 H), 8.31 (d, J = 2.2 Hz, 1 H), 12.34 (s, 1 H). 13C NMR [125 MHz, (CD3)2SO]: δ = 99.82, 107.76, 114.78, 120.09, 125.74, 128.92, 129.14, 130.82, 133.67, 135.44, 141.88, 144.15. MS (EI, 70 eV): m/z (%) = 238 (100) [M+], 208 (29), 192 (36), 191 (27), 190 (14), 165 (22). HRMS (EI): m/z calcd for C14H10N2O2: 238.0742; found: 238.0743. 2-(4-Chlorophenyl)-6-nitroindole (8d) Orange crystals, mp >280 °C (lit.25 260–261 °C). 1H NMR [500 MHz, (CD3)2SO]: δ = 7.15 (br s, 1 H), 7.57–7.61 (m, 2 H), 7.71 (d, J = 8.9 Hz, 1 H), 7.89 (dd, J = 8.9, 2.0 Hz, 1 H), 7.92–7.96 (m, 2 H), 8.27 (d, J = 2.0 Hz, 1 H). 13C NMR [125 MHz, (CD3)2SO]: δ = 100.35, 107.82, 114.85, 120.29, 127.41, 129.18, 129.73, 133.43, 133.54, 135.52, 142.10, 142.82. MS (EI, 70 eV): m/z (%) = 274 (33) [M+ + 2], 272 (100) [M+], 244 (9), 242 (29), 228 (11), 226 (32), 214 (7), 199 (7), 191 (39), 190 (31), 164 (8), 163 (10). HRMS (EI): m/z calcd for C14H9 35ClN2O2: 272.0353; found: 272.0350. 2-(4-Methoxyphenyl)-6-nitroindole (8e) Yellow crystals, mp 235–237 °C (lit. 26 233–234 °C). 1H NMR [500 MHz, (CD3)2SO]: δ = 3.83 (s, 3 H), 7.00 (s, 1 H), 7.07–7.11 (m, 2 H), 7.65 (d, J = 8.7 Hz, 1 H), 7.85–7.89 (m, 2 H), 7.89 (dd, J = 8.7, 2.1 Hz, 1 H), 8.25 (d, J = 2.1 Hz, 1 H), 12.21 (s, 1 H). 13C NMR [125 MHz, (CD3)2SO]: δ = 55.30, 98.64, 107.49, 114.60, 114.82, 119.55, 123.35, 127.26, 134.02, 135.28, 141.42, 144.47, 159.93. MS (EI, 70 eV): m/z (%) = 268 (100) [M+], 253 (6), 252 (5), 238 (20), 222 (35), 207 (19), 191 (9), 179 (6), 178 (11), 152 (8). HRMS (EI): m/z calcd for C15H12N2O3: 268.0848; found: 268.0841. Ethyl 6-Nitroindole-2-carboxylate (8f) Orange crystals, mp 193–195 °C (lit.27 195–197 °C). 1H NMR [500 MHz, (CD3)2CO]: δ = 1.39 (t, J = 7.0 Hz, 3 H), 4.42 (q, J = 7.0 Hz, 2 H), 7.32 (s, 1 H), 7.90 (d, J = 8.8 Hz, 1 H), 7.99 (dd, J = 8.8, 2.2 Hz, 1 H), 8.48 (br s, 1 H), 11.58 (br s, 1 H). 13C NMR [125 MHz, (CD3)2CO]: δ = 13.66, 61.09, 107.65, 109.06, 114.99, 122.79, 131.76, 133.11, 135.71, 145.20, 160.55. MS (EI, 70 eV): m/z (%) = 234 (95) [M+], 206 (5), 189 (22), 188 (100), 143 (11), 142 (32), 130 (13). HRMS (EI): m/z calcd for C11H10N2O4: 234.0641; found: 234.0645. 6-Nitro-2-(trifluoromethyl)indole (8g) Yellow crystals, mp 143–145 °C. 1H NMR [500 MHz, (CD3)2CO]: δ = 7.22 (dq, J = 1.0, 0.9 Hz, 1 H), 7.94 (d, J = 8.7 Hz, 1 H), 8.05 (dd, J = 8.7, 2.1 Hz, 1 H), 8.47 (ddd, J = 2.1, 0.8, 0.8 Hz, 1 H), 12.06 (br s, 1 H).19 F NMR (470 MHz, [CD3)2CO]: δ = –61.80 (d, J = 2.4 Hz). MS (EI, 70 eV): m/z (%) = 230 (100) [M+], 214 (7), 211 (11), 200 (27), 184 (71), 172 (13), 164 (913), 157 (17), 152 (13), 137 (12). HRMS (EI): m/z calcd for C9H5N2O2F3: 230.0303; found: 230.0300. Ethyl 4-Nitroindole-2-carboxylate (8h) Yellow solid, mp 224–226 °C (lit.28 227–229 °C). 1H NMR [500 MHz, (CD3)2SO]: δ = 1.39 (t, J = 7.1 Hz, 3 H), 4.41 (q, J = 7.1 Hz, 2 H), 7.50 (dd, J = 8.0, 8.0 Hz, 1 H), 7.95 (br d, J = 8.0 Hz, 1 H), 8.15 (br d, J = 8.0 Hz, 1 H), 12.77 (br s, 1 H). 13C NMR [(125 MHz, (CD3)2SO]: δ = 14.15, 61.13, 106.31, 118.36, 119.87, 120.59, 123.77, 131.23, 138.88, 141.42, 160.59. MS (EI, 70 eV): m/z (%) = 234 (85) [M+], 206 (5), 189 (24), 188 (100), 158 (14), 143 (13), 142 (36), 130 (12), 115 (14), 114 (47). HRMS (EI): m/z calcd for C11H10N2O4: 234.0641; found: 234.0643. 4-Nitro-2-(trifluoromethyl)indole (8i) Yellow crystals, mp 219–221 °C. 1H NMR [500 MHz, (CD3)2SO]: δ = 7.50 (dq, J = 0.9, 0.8 Hz, 1 H), 7.55 (dd, J = 8.2, 7.9 Hz, 1 H), 8.01 (ddd, J = 8.2, 0.8, 0.8 Hz, 1 H), 8.20 (dd, J = 7.9, 0.8 Hz, 1 H), 13.25 (s, 1 H). 13C NMR [125 MHz, (CD3)2SO]: δ = 102.39 (q, J = 3.4 Hz), 118.48, 119.20, 120.49, 120.81 (q, J = 268.5 Hz), 123.81, 128.82 (q, J = 38.6 Hz), 138.41, 140.41. 19F NMR (470 MHz, CDCl3): δ = –54.86 (d, J = 1.1 Hz). MS (EI, 70 eV): m/z (%) = 230 (100) [M+], 211 (11), 200 (21), 184 (71), 172 (19), 164 (11), 157 (15), 152 (15), 144 (17), 137 (11). HRMS (EI): m/z calcd for C9H5F3N2O2: 230.0303; found: 230.0297
  • 24 Moskalev N, Barbasiewicz M, Mąkosza M. Tetrahedron 2004; 60: 347
    CrossrefSuche in Google Scholar
  • 25 Dennler EB, Frasca AR. Tetrahedron 1966; 22: 3139
    Suche in Google Scholar
  • 26 Kim JS, Sun Q, Gatto B, Yu C, Liu A, Liu LF, LaVoie EJ. Bioorg. Med. Chem. 1996; 4: 621
    CrossrefSuche in Google Scholar
  • 27 Parmerter SM, Cook AG, Dixon WB. J. Am. Chem. Soc. 1958; 80: 4621
    CrossrefSuche in Google Scholar
  • 28 Noland WE, Rush KR. J. Org. Chem. 1966; 31: 70
    CrossrefSuche in Google Scholar