Download PDF
Synlett 2007(10): 1525-1528  
DOI: 10.1055/s-2007-982534
LETTER
© Georg Thieme Verlag Stuttgart · New York

2-Nitroso-N-arylanilines: Products of Acid-Promoted Transformation of σH Adducts of Arylamines and Nitroarenes

Zbigniew Wróbel*, Andrzej Kwast
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44/52, 01-224 Warsaw, Poland
Fax: +48(22)6318788; e-Mail: wrobel@icho.edu.pl;
Further Information

Publication History

Received 29 March 2007
Publication Date:
06 June 2007 (online)

    Permissions and Reprints All articles of this category

Abstract

Anions generated from arylamines react with substituted nitrobenzenes to form σH adducts, which, under protonation with acetic acid, undergo transformation to 2-nitroso-N-arylamines, ­susceptible to reduction, condensation and cyclization reactions.

Key words

nucleophilic - additions - arenes - amines - nitroso group

    References and Notes

  • 1a Terrier F. Nucleophilic Aromatic Displacement - The Influence of the Nitro Group   Verlag Chemie; Weinheim: 1991. 
    Google Scholar
  • 1b Chupakhin ON. Charushin VN. van der Plas HC. Nucleophilic Aromatic Substitution of Hydrogen   Academic Press; San Diego: 1994. 
    Google Scholar
  • 1c Mąkosza M. Russ. Chem. Bull.  1996,  45:  491 
    Google Scholar
  • 2a Mąkosza M. Winiarski J. Acc. Chem. Res.  1987,  20:  282 
    Google Scholar
  • 2b Mąkosza M. Wojciechowski K. Liebigs Ann./Recl.  1997,  1805 
    Google Scholar
  • 2c Mąkosza M. Kwast A. J. Phys. Org. Chem.  1998,  11:  341 
    Google Scholar
  • 3 Suwiński J. Świerczek K. Tetrahedron  2001,  57:  1639 
    Google Scholar
  • 4a Mąkosza M. Staliński K. Pol. J. Chem.  1999,  73:  151 
    Google Scholar
  • 4b Mąkosza M. Staliński K. Tetrahedron  1998,  54:  8797 
    Google Scholar
  • 4c Mąkosza M. Staliński K. Chem. Eur. J.  2001,  7:  2025 
    Google Scholar
  • 4d Adam W. Mąkosza M. Zhao CG. Surowiec M. J. Org. Chem.  2000,  65:  1099 
    Google Scholar
  • 5a Wróbel Z. Tetrahedron Lett.  1997,  38:  4913 
    Google Scholar
  • 5b Wróbel Z. Tetrahedron  1998,  54:  2607 
    Google Scholar
  • 6 Wróbel Z. Eur. J. Org. Chem.  2000,  521 
    Google Scholar
  • 7 Wróbel Z. Pol. J. Chem.  1998,  72:  2384 
    Google Scholar
  • 8 Wróbel Z. Synlett  2004,  1929 
    Google Scholar
  • 9a Wohl A. Aue W. Ber. Dtsch. Chem. Ges.  1901,  34:  2442 
    Google Scholar
  • 9b Wohl A. Ber. Dtsch. Chem. Ges.  1903,  36:  4135 
    Google Scholar
  • 9c Serebryanyi SB. Ukr. Khim. Zh. (Russ. Ed.)  1955,  21:  350 
    Google Scholar
  • 10a Stern MK. Hileman FD. Bashkin JK. J. Am. Chem. Soc.  1992,  114:  9237 
    Google Scholar
  • 10b Beska E, Toman P, Fiedler K, Hronec M, and Pinter J. inventors; US Patent  6388136. 
  • 11 Lipilin DL. Churakov AM. Ioffe SL. Strelenko YA. Tartakowsky VA. Eur. J. Org. Chem.  1999,  29 
    Google Scholar
  • 12 Lemek T. Mąkosza M. Stephenson DS. Mayr H. Angew. Chem. Int. Ed.  2003,  42:  2793 
    Google Scholar
  • 13 Bażej S. Kwast A. Mąkosza M. Tetrahedron Lett.  2004,  45:  3193 
    Google Scholar
  • 14a Bartoli G. Rosini G. Synthesis  1976,  270 
    Google Scholar
  • 14b Bartoli G. Leardini R. Medici A. Rosini G. J. Chem. Soc., Perkin Trans. 1  1978,  692 
    Google Scholar
  • 16a Fasani E. Pietra S. Albini A. Heterocycles  1992,  33:  573 
    Google Scholar
  • 16b Fasani E. Mella M. Albini A. J. Chem. Soc., Perkin Trans. 1  1992,  2689 
    Google Scholar
  • 16c Titova SP. Arinich AK. Gorelik MV. J. Org. Chem. USSR (Eng. Transl.)  1986,  1407 
    Google Scholar
  • 16d Okubo M. Inatomi Y. Taniguchi N. Imamura K. Bull. Chem. Soc. Jpn.  1988,  61:  3581 
    Google Scholar
  • 17 Holschbach MH. Sanz D. Claramunt RM. Infantes L. Motherwell S. Raithby PR. Jimeno ML. Herrero D. Alkorta I. Jagerovic N. Elguero J. J. Org. Chem.  2003,  68:  8831 
    Google Scholar
  • 18 Urbelis G. Susvilo I. Tumkevicius S. J. Mol. Model.  2007,  13:  219 
    Google Scholar
  • 19 Buckley PD. Furness AR. Jolley KW. Pinder DN. Austr. J. Chem.  1974,  27:  21 
    Google Scholar
  • 20 Tsui K. Nakamura K. Konishi N. Okumura H. Matsuo M. Chem. Pharm. Bull.  1992,  40:  2399 
    Google Scholar
  • 21 Barluenga J. Fananas FJ. Sanz R. Fernandez Y. Chem. Eur. J.  1965,  397 
    Google Scholar
  • 22 Mangini A. Gazz. Chim. Ital.  1935,  65:  1191 
    Google Scholar
  • 23 Vivian DL. J. Am. Chem. Soc.  1951,  73:  457 
    Google Scholar
15

Melting points are uncorrected. 1H and 13C NMR spectra were recorded on a Varian Mercury 400 instrument (400 MHz for 1H NMR and 100 MHz for 13C NMR spectra) in CDCl3. Chemical shifts (δ) are expressed in ppm referred to TMS, and coupling constants are given in Hz. 15N GHMBC experiment was performed on a Bruker 500 instrument in CDCl3 at 273 K. Mass spectra (EI, 70 eV) were obtained on an AMD-604 spectrometer. Silica gel Merck 60 (230-400 mesh) was used for column chromatography.
2-Chloro-4-trifluoromethylonitrobenzene [20] (2d) and 4-chloro-2-methoxynitrobenzene [21] (2e) were obtained according to the literature. All other reagents are commercially available.
Preparation of 2-Nitroso- N -arylanilines 3a-i; General Procedure
To a cooled solution of t-BuOK (6 mmol, 672 mg) in DMF (2 mL) was added dropwise at -60 °C a solution of aniline 1 (2 mmol) in DMF (1 mL) and nitroarene 2 (2 mmol) in DMF (1 mL). The mixture was stirred at this temperature for 2-5 min, and then a cooled mixture of AcOH (1.5 mL) and DMF (1.5 mL) was added in one portion. The cooling bath was removed and the mixture was allowed to reach the ambient temperature, then it was poured into H2O (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-benzene) to obtain products 3a-i. The representative examples of 3 are described below. 3a: Brown solid; mp 124-125 °C. 1H NMR: δ = 7.09 (dd, J = 1.4, 10.2 Hz, 1 H), 7.05 (d, J = 1.7, 8.8 Hz, 1 H), 7.17-7.24 (m, 2 H), 7.39-7.45 (m, 2 H), 8.68 (br s, 1 H), 11.82 (br s, 1 H). 13C NMR: δ = 114.0, 119.1, 126.1, 130.0, 132.2, 135.0, 140.4 (br), 144.8, 154.9, one signal not observed. MS (EI): m/z (%) = 268 (7), 266 (11), 251 (66), 249 (100), 237 (18), 235 (26), 201 (22). HRMS (EI): m/z [M]+ calcd for C12H8ON2 35Cl2: 266.0014; found: 266.0024.
3d: Brown solid; mp 96-97 °C (hexane-benzene). 1H NMR: δ = 2.38 (s, 3 H), 6.93 (d, J = 8.6 Hz, 1 H), 7.05 (d, J = 2.0 Hz, 1 H), 7.13 (br d, J = 8.2 Hz, 2 H), 7.23 (br d, J = 8.2 Hz, 2 H), 8.67 (br s, 1 H), 12.08 (br s, 1 H). 13C NMR: δ = 114.4, 118.5, 120.2, 124.9, 130.4, 133.4, 136.9, 141.8 (very br), 144.6, 154.9, one signal not observed. MS (EI): m/z (%) = 245 (6), 231 (42), 229 (100), 214 (22), 180 (25). HRMS (LSI): m/z [M + H]+ calcd for C13H12ON2 35Cl: 247.0632; found: 247.0621. 3f: Brown solid; mp 106-107 °C. 1H NMR (500 MHz, CDCl3, -15 °C): δ = 2.37 (s, 3 H), 3.76 (s, 3 H), 6.35 (d, J = 2.1 Hz, 1 H), 6.57 (dd, J = 2.1, 9.2 Hz, 1 H), 7.17-7.25 (m, 4 H), 8.48 (d, J = 9.2 Hz, 1 H), 12.97 (br s, 1 H). 13C NMR: δ = 20.9, 55.7, 93.5, 109.3, 124.7, 130.2, 133.9, 136.4, 137.7, 142.4, 153.6, 167.0. 15N NMR (GHMBC, CDCl3, δ relative to MeNO2, 273 K): δ = -286.5 (N=O), 334 (J NH = 91.9 Hz, NH). MS (EI): m/z (%) = 242 (16), 241 (15), 225 (100), 210 (15), 196 (15), 182 (21). HRMS (EI): m/z [M]+ calcd for C14H14O2N2: 242.1055; found: 242.1051.
Reduction of 3d with Zn/AcOH: To a solution of 2-nitroso-N-(4-tolyl)aniline 3d (0.15 mmol, 37.2 mg) in AcOH (1 mL), powdered Zn (150 mg) was added and the mixture was stirred at ambient temperature, while monitored by TLC. After the substrate had disappeared (ca. 1.5 h), the mixture was diluted with EtOAc (10 mL), filtered, washed with H2O, sat. NaHCO3 and H2O, and then dried with Na2SO4. The solvent was evaporated and the crude product was purified by column chromatography (SiO2, hexane-EtOAc, 5:1) to give 4a (26.2 mg, 75%).
4a: Brown solid; mp 65-66 °C(hexane) [Lit. [22] 66.5-67.5 °C (PE)]. 1H NMR: δ = 2.68 (s, 3 H), 3.64 (br s, 2 H), 5.10 (br s, 1 H), 6.69 (d, J = 8.4 Hz, 1 H), 6.72-6.76 (m, 2 H), 6.89 (dd, J = 2.3, 8.4 Hz, 1 H), 7.04-7.08 (m, 3 H). 13C NMR: δ = 20.6, 116.9, 117.0, 121.7, 123.7, 123.8, 129.9, 130.0, 131.5, 138.6, 141.3. MS (EI): m/z (%) = 232 (100), 217 (59). HRMS (EI): m/z [M]+ calcd for C13H13N2 35Cl: 232.0767; found: 232.0772.
Catalytic Hydrogenation of 3d: 2-Nitroso-N-(4-tolyl)aniline 3d (0.22 mmol, 55 mg), suspended (partially soluble) in MeOH (1 mL), Et3N (0.44 mmol, 44 mg) and Pd/C (10%, 25 mg) were stirred under H2 at r.t. for 30 min. The catalyst was filtered off and the solution was evaporated to dryness. The residue was diluted with EtOAc (10 mL) and H2O (5 mL), and the organic layer was separated, washed with H2O and dried with Na2SO4. After evaporation of the solvents, the crude product was purified by column chromatography (SiO2, hexane-EtOAc, 4:1) to deliver 4b (37 mg, 84%).
4b: Brown solid; mp 77 °C(hexane). 1H NMR: δ = 2.26 (s, 3 H), 3.67 (br s, 2 H), 5.26 (br s, 1 H), 6.65 (m, 2 H), 6.71-6.76 (m, 1 H), 6.78 (dd, J = 1.2, 7.8 Hz, 1 H), 6.95-7.00 (m, 1 H), 7.00-7.05 (m, 2 H), 7.08 (dd, J = 1.4, 7.8 Hz, 1 H). 13C NMR: δ = 20.4, 115.8, 116.1, 119.1, 123.8, 125.0, 128.8, 129.4, 129.8, 141.3, 142.62. MS (EI): m/z (%) = 198 (100), 183 (64), 91 (18). HRMS (EI): m/z [M]+ calcd for C13H14N2: 198.1157; found: 198.1147.
Cyclization of 3a to 2,7-Dichlorophenazine ( 5): 2-Nitroso-N-(4-chlorophenyl)aniline 3a (0.1 mmol, 25 mg) in AcOH (3 mL) was refluxed for 1.5 h. After cooling down, the mixture was diluted with H2O and the precipitated crude product was filtered off. Recrystallization from EtOH gave pure 5 (20 mg (80%).
5: Pale yellow solid; mp 265-266 °C (Lit. [23] 266-268 °C). MS (EI): m/z (%) = 250 (64), 248 (100), 213 (33).
Condensation of 3a with Methyl Malonate: 2-Nitroso-N-(4-chlorophenyl)aniline 3a (0.067 mmol, 18 mg), methyl malonate (0.14 mmol, 18 mg) and K2CO3 (75 mg) were stirred in MeCN (1 mL) at r.t. for 30 min. The mixture was diluted with MeCN, filtered and evaporated. The crude product was purified by column chromatography (SiO2, hexane-EtOAc, 5:1) to obtain pure 6 (20 mg, 85%).
6: Yellowish crystals; mp 160-161 °C. 1H NMR: δ = 4.03 (s, 3 H), 6.71 (d, J = 2.2 Hz, 1 H), 7.23-7.27 (m, 2 H), 7.35 (dd, J = 2.2, 8.6 Hz, 1 H), 7.60-7.65 (m, 2 H), 7.92 (d, J = 8.6 Hz, 1 H). 13C NMR: δ = 55.3, 115.2, 125.2, 129.5, 130.2, 130.9, 132.1, 132.8, 135.5, 136.3, 138.9, 148.8, 151.8, 163.4. MS (EI): m/z (%) = 350 (31), 348 (48), 263 (67), 261 (100), 226 (24), 191 (21). HRMS (EI): m/z [M]+ calcd for C16H10N2O3 35Cl2: 348.0068; found: 348.0076.