Tribromoisocyanuric Acid in Trifluoroacetic Acid: An Efficient System for Smooth Brominating of Moderately Deactivated Arenes

Abstract

Moderately deactivated arenes are efficiently brominated by the reaction with tribromoisocyanuric acid (0.34 mol equiv) in trifluoroacetic acid at room temperature in 48–85% isolated yield. This medium avoids the polybromination of the substrate, ­observed in the same reaction performed in 98% H₂SO₄.

Key words

arenes - electrophilic halogenation - bromination - de­activated aromatic compounds - tribromoisocyanuric acid

• References and Notes

• 1 Trzeeciak JJ, Ziolkowski J. J. Coord. Chem. Rev. 2007; 251: 1281
• 2a Felício LF, Nasello AG. Braz. J. Med. Biol. Res. 1989; 22: 1011
• 2b Winsel K, Grollmuss H, Unger U, Renner H. Pharmazie 1986; 41: 796
• 2c Dubinsky B, Mcguire JL, Niemegeers CJ. E, Janssen PA. J, Weintraub HS, Mckenzie BE. Psychopharmacology 1982; 78: 1
• 3a Cristiano R, Ma K, Pottanat G, Weiss RG. J. Org. Chem. 2009; 74: 9027
• 3b Khazaei A, Zolfigol MA, Kolvari E, Koukabi N, Soltani H, Komari F. Synthesis 2009; 3772
• 3c de Almeida LS, Esteves PM, de Mattos MC. S. Synlett 2007; 1687
• 3d Joshi A, Baidossi M, Mukhopadhyay S, Sasson Y. Org. Process Res. Dev. 2004; 8: 568
• 4 Andrievsky AM, Gorelik MV. Russ. Chem. Rev. 2011; 80: 421
• 5a de Almeida LS, Esteves PM, de Mattos MC. S. Synlett 2006; 1515
• 5b Tozetti SD. F, de Almeida LS, Esteves PM, de Mattos MC. S. J. Braz. Chem. Soc. 2007; 18: 675
• 6 de Almeida LS, Esteves PM, de Mattos MC. S. Synthesis 2006; 221
• 7 Mendonça GF, Sindra HC, de Almeida LS, Esteves PM, de Mattos MC. S. Tetrahedron Lett. 2009; 50: 473
• 8 de Almeida LS, Esteves PM, de Mattos MC. S. Tetrahedron Lett. 2009; 50: 3001
• 9a Ribeiro RS, Esteves PM, de Mattos MC. S. J. Braz. Chem. Soc. 2012; 23: 228
• 9b Crespo LT. C, Ribeiro RS, de Mattos MC. S, Esteves PM. Synthesis 2010; 2379
• 9c Ribeiro RS, Esteves PM, de Mattos MC. S. J. Braz. Chem. Soc. 2008; 19: 1239
• 9d Mendonça GF, de Mattos MC. S. Quim. Nova 2008; 31: 798
• 9e Ribeiro RS, Esteves PM, de Mattos MC. S. Tetrahedron Lett. 2007; 48: 8747
• 9f Souza AV. A, Mendonça GF, Bernini RB, de Mattos MC. S. J. Braz. Chem. Soc. 2007; 18: 1575
• 10 Mendonça GF, Senra MR, Esteves PM, de Mattos MC. S. Appl. Catal., A 2011; 401: 176
• 11 Same results were also obtained by Prakash using the system NBS/BF₃–H₂O as brominating reagent: Prakash GK. S, Mathew T, Hoole D, Esteves PM, Wang Q, Rasul G, Olah GA. J. Am. Chem. Soc. 2004; 126: 15770
• 12 da Ribeiro RS, Esteves PM, de Mattos MC. S. Synthesis 2011; 739
• 13 Typical Procedure for the Bromination of Arenes with TBCA/TFA To a well-stirred solution of TBCA (0.67 mmol) in TFA (10 mL), arene (2 mmol) was slowly added at r.t. After the end of the reaction (determined by HRGC), the reaction mixture was poured into ice (ca. 100 g) and then treated with 10% NaHSO₃ (10 mL). After warm up to r.t., the solution was extracted with CH₂Cl₂ (3 × 10 mL), and the combined extracts were dried over anhyd Na₂SO₄. Selected Analytical Data 4-Fluorobromobenzene MS (70 eV): m/z (%) = 176 [M⁺ + 2], 174 [M⁺], 143, 141, 119, 117, 95 (100), 75, 50. ¹H NMR (200 MHz, CDCl₃): δ = 6.94 (t, 2 H, J = 8.54 Hz), 7.44 (dd, 2 H, J ₁ = 8.54 Hz, J ₂ = 4.78 Hz) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 116.5 (d, J = 3.1 Hz), 117.2 (d, J = 23.0 Hz), 132.9 (d, J = 8.00 Hz), 161.9 (d, J = 246.5 Hz) ppm. Methyl 3-bromobenzoate MS (70 eV): m/z (%) = 216 [M⁺ + 2], 214 [M⁺], 185, 183 (100), 157, 155, 135, 119, 76, 75, 74, 50. ¹H NMR (200 MHz, CDCl₃): δ = 3.89 (s, 3 H), 7.28 (t, 1 H, J = 7.85 Hz), 7.65 (d, 1 H, J = 7.85 Hz), 7.93 (d, 1 H, J = 7.85 Hz), 8.14 (s, 1 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 52.3, 122.4, 128.1, 129.8, 132.0, 132.5, 135.8, 165.7 ppm 3-Bromobenzoic Acid Mp 156–158 °C (from EtOH), lit.¹⁴ 155–158 °C. ¹H NMR (200 MHz, CDCl₃): δ = 7.44 (t, 1 H, J = 7.85 Hz), 7.79 (d, 1 H, J = 7.85 Hz), 7.91 (d, 1 H, J = 7.51 Hz), 8.01 (s, 1 H), 11.17 (s) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 121.7, 128.3, 130.9, 131.8, 133.1, 135.6, 166.1 ppm. 3-Bromo(trifluoromethyl)benzene MS (70 eV): m/z (%) = 226 [M⁺ + 2], 224 [M⁺], 207, 205, 176, 174, 157, 155, 145 (100), 95, 75, 69, 50. ¹H NMR (200 MHz, CDCl₃): δ = 7.35 (t, 1 H, J = 7.86 Hz), 7.56 (d, 1 H, J = 7.90 Hz), 7.68 (d, 1 H, J = 7.86 Hz), 7.77 (s, 1 H) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 122.7 (s), 123,2 (q, J = 272.6 Hz), 123.9 (q, J = 3.8 Hz), 128.54 (q, J = 3.8 Hz), 130.4 (s), 132.5 (d, J = 32.9 Hz), 135.0 (s) ppm. 2-Bromo-4-nitrotoluene Mp 76–78 °C (from EtOH), lit.¹⁵ 74–76 °C. MS (70 eV): m/z (%) = 217 [M⁺ + 2], 215 [M⁺], 187, 185, 171, 169, 159, 157, 145, 143, 119, 117, 105, 90 (100), 89, 78, 63. ¹H NMR (200 MHz, CDCl₃): δ = 2.48 (s, 3 H), 7.38 (d, 1 H, J = 8.53 Hz), 8.04 (dd, 1 H, J₁ = 8.53 Hz, J₂ = 2.39 Hz), 8.36 (d, 1 H, J = 2.39 Hz) ppm. ¹³C NMR (75 MHz, CDCl₃): δ = 23.1, 122.1, 124.9, 127.34, 131.0, 145.8, 146.6 ppm. 3-Bromo-4-iodonitrobenzene Mp 47–48 °C (from hexane), lit.¹⁶ 49–50 °C. 1-Bromo-2,3,4-trichlorobenzene Mp 60–61 °C (from MeOH), lit.¹⁷ 74–76 °C. 5-Bromoisatin ¹H NMR (200 MHz, DMSO-d ₆): δ = 6.87 (d, 1 H, J = 8.12 Hz), 7.52 (m, 2 H), 11.03 (1 H, s_br) ppm. ¹³C NMR (75 MHz, DMSO-d ₆): δ = 113.8, 114.7, 118.3, 126.9, 139.8, 149.1, 158.3, 182.9 ppm.
• 14 Cohen JB, Dutt PK. J. Chem. Soc. 1914; 105: 501
• 15 Truce WE, Amos MF. J. Am. Chem. Soc. 1951; 73: 3013
• 16 Archer GA, Kalish RI, Ning RY, Sluboski BC, Stempel A, Steppe TV, Sternbach LH. J. Med. Chem. 1977; 20: 1312
• 17 Scott R, Hawner C, Johansen JE. Tetrahedron 2008; 64: 4135