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Synlett 2006(12): 1956-1958  
DOI: 10.1055/s-2006-944231
LETTER
© Georg Thieme Verlag Stuttgart · New York

Three-Step Synthesis of Highly Substituted Phenols from 1,3-Dinitropropanes

Roberto Ballini*, Luciano Barboni*, Guido Giarlo, Alessandro Palmieri
Dipartimento di Scienze Chimiche, Università di Camerino, Via S. Agostino 1, 63032 Camerino, Italy
Fax: +39(0737)402297; e-Mail: roberto.ballini@unicam.it;
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Publication History

Received 13 February 2006
Publication Date:
24 July 2006 (online)

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Abstract

Reaction of 1,3-dinitropropanes with acrolein under heterogeneous conditions (neat Al2O3) gives dinitrocyclohexanols, which, by treatment with potassium carbonate followed by acidic work-up, allow access to nitrocyclohexenone derivatives. The latter, by reaction with phenyltrimethylammonium tribromide, concludes a three-step synthesis of nitro-dibromophenols in satisfactory yields.

Key words

bromophenols - aromatization - 1,3-dinitroalkanes - Nef reaction - nitrocyclohexanols

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Preparation of Nitrodibromophenols 4; General Procedure
To a stirred mixture of dinitroalkane 1 (2 mmol) and acrolein (2.6 mmol, 0.174 mL) was added, at 0 °C, basic Al2O3 (2 g, activity I). The resulting mixture was stirred at the same temperature for 15 min, then at r.t. for the appropriate reaction time (Table [1] ). The heterogeneous mixture was directly charged onto a chromatography column (EtOAc-hexane) giving the pure compound 2.13 To a solution of 2 (1 mmol) in H2O-MeOH (1:1, 10 mL), K2CO3 (0.2 g, 2 mmol) was added at r.t. After stirring for 15 min, the solution was acidified with 4 N HCl (pH 2-3) and left at r.t. for 30 min. The organic solution was washed with NaHCO3 (3 × 5 mL), brine (1 × 10 mL), and then evaporated. The residue was dissolved in CH2Cl2 (20 mL), followed by the addition of PhN(CH3)3Br·Br2 (0.38 g, 1 mmol). The solution obtained after stirring overnight at r.t. was treated with DBU until the color changed, and the reaction was left to proceed for 1 h. The mixture was washed with H2O (2 × 5 mL), brine (10 mL), and the organic layer was dried (MgSO4), concentrated, and purified by flash chromatography (SiO2, hexane-EtOAc) giving pure compounds 4.
Compound 4a: 1H NMR (CDCl3, 200 MHz): δ = 0.89 (m, 3 H), 1.32 (m, 4 H), 1.58 (m, 2 H), 2.59 (m, 2 H), 5.90 (br s, 1 H), 7.63 (s, 1 H). 13C NMR (CDCl3, 50 MHz) δ = 14.1, 22.4, 27.8, 28.9, 31.9, 103.0, 112.3, 124.8, 132.97, 132.98, 105.8. GC-MS (70 eV): m/z = 367 [M+]. Anal. Calcd for C11H13Br2NO3: C, 36.0; H, 3.57; N, 3.82. Found: C, 36.31; H, 3.66; N, 3.69. Compound 4e: 1H NMR (CDCl3, 200 MHz): δ = 7.22 (d, 2 H, J = 8.2 Hz), 7.51 (d, 2 H, J = 8.2 Hz), 7.64 (s, 1 H), 9.38 (br s, 1 H). 13C NMR (CDCl3, 50 MHz) δ = 101.9, 112.6, 114.5, 118.2, 123.0, 130.4, 132.1, 136.0, 136.1, 150.7. GC-MS (70 eV): m/z = 398 [M+]. Anal. Calcd for C13H6Br2N2O3: C, 39.23; H, 1.52; N, 7.04. Found: C, 39.45; H, 1.61; N, 6.89. Compound 4g: 1H NMR (CDCl3, 200 MHz): δ = 7.37 (m, 2 H), 7.80 (td, 1 H, J = 7.8, 2.0 Hz), 8.27 (s, 1 H), 8.65 (d, 1 H, J = 4.3 Hz). 13C NMR (CDCl3, 50 MHz): δ = 110.2, 123.1, 123.7, 124.3, 129.0, 131.0 (2 C), 137.2, 150.0, 150.5, 150.7. GC-MS (70 eV): m/z = 294 [M+ - Br]. Anal. Calcd for C11H6Br2N2O3: C, 35.33; H, 1.62; N, 7.49. Found: C, 35.54; H, 1.73; N, 7.28.