Simple Bromination of Activated Arenes by IBX Amide Resin and Tetraethylammonium Bromide

Abstract

A mild and operationally simple method of brominating activated aromatic compounds using a polymer supported IBX reagent (IBX amide resin) and tetraethylammonium bromide (TEAB) was developed. The activated aromatics, when reacted with IBX amide resin in the presence of TEAB, were easily converted into the brominated aromatics in high yields (>80%) at room temperature.

Key words

bromination - IBX amide - tetraethylammonium bromide

References

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14

Thionyl chloride (5.9 mL) was added to 2 g (8 mmol) of 2-iodobenzoic acid under stirring and was refluxed for 1 h. After cooling the reaction mixture, excess thionyl chloride was removed in vacuo to give the 2-iodobenzoyl chloride which was used without further purification. To a solution of the above 2-iodobenzoyl chloride in CH₂Cl₂, 2 equiv of benzyl amine (1.76 mL) were added and the mixture was stirred at r.t. for 2 h. The reaction mixture was washed with EtOAc and the solvent was removed in vacuo. The crude product was purified by dry column chromatography affording the desired N-benzyl-2-iodobenzamide (2.4 g, yield 88%). ¹H NMR (300 MHz, CDCl₃, 25 °C): d = 7.85 (d, 1 H, J = 9 Hz), 7.25-7.42 (m, 7 H), 7.05-7.11 (m, 1 H), 6.05 (s, 1 H), 4.64 (d, 2 H, J = 6 Hz). To a solution of N-benzyl-2-iodobenzamide (2.4 g, 7.1 mol) in CH₂Cl₂ (50 mL), oxone (5.7 g, 1.3 equiv) was added. The reaction mixture was warmed to 40-45 °C over 20 min and stirred at this temperature for 24 h (0.21 g, yield 20%). ¹H NMR (300 MHz, DMSO-d ₆, 25 °C): d = 9.89 (t, 1 H, J = 6 Hz), 8.30 (d, 1 H, J = 6 Hz), 8.22 (d, 1 H, J = 6 Hz), 7.95 (t, 1 H, J = 15 Hz), 7.75 (t, 1 H, J = 15 Hz), 7.27-7.36 (m, 5 H), 4.58 (d, 2 H, J = 6 Hz).

15

2,6-Dichlorophenol (22 mg, 0.135 mmol) was added to a solution of IBX amide (100 mg, 0.27 mmol) and TEAB (57 mg, 0.27 mmol) in DMSO (2 mL). After 0.5 h, the reaction mixture was diluted with H₂O (20 mL), extracted with Et₂O (6 × 20 mL), and the organic layers was dried (MgSO₄) and evaporated. The crude product was purified by dry column chromatography to give 4-bromo-2,6-dichlorophenol (30.6 mg, yield 94%).