Efficient Electrophilic Cobromination of Alkenes and Bromination of Activated Arenes with Bromodichloroisocyanuric Acid under Mild Conditions

Abstract

Efficient methodologies for the preparation of bromo­dichloroisocyanuric acid were developed (70-75%). This new ­reagent is very efficient for regioselective electrophilic bromination of activated arenes (86-93%) and cobromination of alkenes with oxygenated nucleophiles (31-98%). The reaction of bromodi­chloroisocyanuric acid with anisole, acetanilide, N-methyl­acetanilide leads to 4-substituted monobromoarene and with 2-methoxynaphthalene leads to 1-bromo-2-methoxynaphthalene. Alkenes were cobrominated in the presence of oxygenated nucleophilic solvents (water, alcohols, and acetic acid), leading to the corresponding bromohydrins, β-bromoethers and β-bromoacetates.

alkenes - arenes - electrophilic addition - electrophilic ­aromatic substitution - halogenation

References and Notes

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10

CP-MAS ¹³C NMR: δ = 159.5 (br, C=O) ppm. IR: 1697, 1654, 1620, 1484, 1450, 1421, 1409, 1349, 1319, 1203, 1149, 1110, 1074, 1047, 796, 755, 725, 602, 555 cm^-1.

11

Selected Analytical Data
1-Bromo-2-phenylpropan-2-ol
¹H NMR (CDCl₃): δ = 1.68 (s, 3 H), 2.63 (s, 1 H), 3.73 (dd, 2 H, J ₁ = 12.45 Hz, J ₂ = 10.20 Hz), 7.25-7.49 (m, 5 H) ppm. ¹³C NMR (CDCl₃): δ = 28.0, 46.2, 73.1, 124.8, 127.5, 128.4, 144.2 ppm. MS (70 eV): m/z = 216 [M⁺ + 2], 214 [M⁺], 199, 201, 121 (100), 77, 43.
(2-Bromo-1-methoxyethyl)benzene ¹H NMR (CDCl₃): δ = 3.31 (s, 3 H), 3.42-3.59 (m, 2 H), 4.39 (dd, 1 H, J ₁ = 7.86 Hz, J ₂ = 4.44 Hz), 7.34-7.43 (m, 5 H) ppm. ¹³C NMR (CDCl₃): δ = 36.2, 57.2, 83.4, 126.7, 128.6, 139.0 ppm. MS (70 eV): m/z = 216 [M⁺ + 2], 214 [M⁺], 121 (100), 91, 77, 51.
(2-Bromo-1-isopropoxyethyl)benzene
¹H NMR (CDCl₃): δ = 1.12 (d, 3 H, J = 6.15 Hz), 1.23 (d, 3 H, J = 6.14 Hz), 3.38-3.48 (m, 2 H), 3.57 (hept, 1 H, J = 6.14 Hz), 4.58 (dd, 1 H, J ₁ = 7.86 Hz, J ₂ = 4.78 Hz) 7.35 (s, 5 H) ppm. ¹³C NMR (CDCl₃): δ = 21.2, 23.1, 37.0, 70.4, 79.3, 126.7, 128.2, 128.5, 140.6 ppm. MS (70 eV): m/z = 185, 183, 149, 107 (100), 79, 43.
2-Bromo-1-phenylethyl Acetate ¹H NMR (CDCl₃): δ = 2.13 (s, 3 H), 3.54 (m, 2 H), 5.98 (dd, 1 H, J ₁ = 7.41 Hz, J ₂ = 5.12 Hz), 7.36 (s, 5 H) ppm. ¹³C NMR (CDCl₃): δ = 20.9, 34.2, 74.8, 126.5, 128.6, 137.6, 169.8 ppm. MS (70 eV): m/z = 244 [M⁺ + 2], 242 [M⁺], 162, 121, 120, 103, 77, 43 (100).
2-Bromo-1-phenylethanol ¹H NMR (CDCl₃): δ = 2.81 (d, 1 H, J = 2.73 Hz) 3.48-3.64 (m, 2 H), 4.89-4.94 (m, 1 H), 7.37 (s, 5 H) ppm. ¹³C NMR (CDCl₃): δ = 40.1, 73.7, 125.9, 128.4, 128.6, 140.3 ppm. MS (70 eV): m/z = 202 [M⁺ + 2], 200 [M⁺], 107 (100), 79, 77, 51.
trans -2-Bromo-1-methylcyclohexanol ¹H NMR (CDCl₃): δ = 1.25-1.48 (m, 5 H), 1.68-2.05 (m, 4 H), 2.15 (br s, 1 H), 2.21-2.27 (m, 1 H), 4.15 (dd, 1 H, J ₁ = 11.52 Hz, J ₂ = 4.10 Hz) ppm. ¹³C NMR (CDCl₃): δ = 22.8, 23.2, 26.3, 34.7, 38.2, 66.0, 72.5. MS (70 eV): m/z = 194 [M⁺ + 2], 192 [M⁺], 177, 179, 113, 95, 71 (100), 43 ppm.
trans -1-Bromo-2-methoxycyclohexane
¹H NMR (CDCl₃): δ = 1.20-1.40 (m, 3 H), 1.64-1.88 (m, 3 H), 2.15-2.34 (m, 2 H), 3.17-3.28 (m, 1 H), 3.42 (ddd, 1 H, J ₁ = 9.56 Hz, J ₂ = 8.53 Hz, J ₃ = 4.44 Hz) ppm. ¹³C NMR (CDCl₃): δ = 23.1, 25.3, 29.9, 35.4, 55.2, 57.1, 83.1 ppm. MS (70 eV): m/z = 194 [M⁺ + 2], 192 [M⁺], 113, 81, 71 (100), 41.
trans -1-Bromo-2-isopropoxycyclohexane ¹H NMR (CDCl₃): δ = 1.13-1.43 (m, 9 H), 1.62-1.90 (m, 3 H), 2.02-2.11 (m, 1 H), 2.30-2.37 (m, 1 H), 3.33-3.40 (m, 1 H), 3.78 (hept, 1 H, J = 6.15 Hz), 3.90 (ddd, 1 H, J ₁ = 9.76 Hz, J ₂ = 8.93 Hz, J ₃ = 4.43 Hz) ppm. ¹³C NMR (CDCl₃): δ = 27.5, 23.0, 23.5, 25.5, 32.5, 35.8, 56.6, 71.2, 79.7 ppm. MS (70 eV): m/z = 222 [M⁺ + 2], 220 [M⁺], 178, 180, 99, 81 (100), 57, 43.
trans -2-Bromocyclohexyl acetate ¹H NMR (CDCl₃): δ = 1.27-1.47 (m, 3 H), 1.74-1.96 (m, 3 H), 2.08 (s, 3 H), 2.13 (m, 1 H), 2.32-2.39 (m, 1 H), 3.96 (ddd, 1 H, J ₁ = 10.45 Hz, J ₂ = 9.29 Hz, J ₃ = 4.26 Hz), 4.84-4.93 (m, 1 H) ppm. ¹³C NMR (CDCl₃): δ = 21.0, 23.3, 25.6, 35.7, 52.8, 75.8, 170.0 ppm. MS (70 eV): m/z = 222 [M⁺ + 2], 220 [M⁺], 160, 162, 81, 43 (100).
trans -2-Bromocyclohexanol ¹H NMR (CDCl₃): δ = 1.24-1.37 (m, 3 H), 1.67-1.86 (m, 3 H), 2.10-2.20 (m, 1 H), 2.25-2.60 (m, 2 H), 3.50-3.70 (m, 1 H), 3.90 (ddd, 1 H, J ₁ = 11.68 Hz, J ₂ = 9.57 Hz, J ₃ = 4.35 Hz) ppm. ¹³C NMR (CDCl₃): δ = 24.1, 26.6, 33.5, 36.2, 61.8, 75.3 ppm. MS (70 eV): m/z = 180 [M⁺ + 2], 178 [M⁺], 99, 81 (100), 57, 41.

12

Selected Analytical Data
4-Bromoanisole ¹H NMR (CDCl₃): δ = 3.77 (s, 3 H), 6.78 (d, J = 8.90 Hz, 2 H), 7.37 (d, J = 8.90 Hz, 2 H) ppm. ¹³C NMR (CDCl₃): δ = 55.4, 112.8, 115.7, 139.2, 158.7 ppm. MS (70 eV): m/z = 188 (100) [M⁺ + 2], 186 (100) [M⁺], 173, 171, 145, 143, 119, 117, 84, 63, 49 ppm.

4-Bromo- N -methylacetanilide Mp 91 °C (lit.¹³ 95 °C). ¹H NMR (CDCl₃): δ = 1.83 (s, 3 H), 3.20 (s, 3 H), 7.04, (d, J = 8.30 Hz, 2 H), 7.50 (d, J = 8.30 Hz, 2 H). ¹³C NMR (CDCl₃): δ = 22.4, 37.0, 121.4, 128.7, 132.9, 143.5, 205.6. MS (70 eV): m/z = 229 [M⁺ + 2], 227 [M⁺], 187 (100), 185 (100), 186, 184, 157, 155, 104, 77, 56, 43.
4-Bromoacetanilide Mp 166 °C (lit.¹⁴ 167 °C). ¹H NMR (DMSO-d ₆): δ = 2.03 (s, 3 H), 7.43, (d, J = 8.92 Hz, 2 H), 7.54 (d, J = 8.92 Hz, 2 H) ppm. ¹³C NMR (DMSO-d ₆): δ = 24.0, 114.5, 120.8, 131.5, 138.7, 168.5 ppm. MS (70 eV): m/z = 215 [M⁺ + 2], 213 [M⁺], 173 (100), 171 (100), 157, 155, 92, 43.
1-Bromo-2-methoxynaphthalene Mp 82 °C (lit.¹⁵ 85 °C). ¹H NMR (CDCl₃): δ = 4.03 (s, 3 H), 7.26 (d, J = 9.67 Hz, 1 H), 7.41 (t, J = 7.90 Hz, 1 H), 7.59 (t, J = 7.90 Hz, 1 H), 7.80 (d, J = 7.9 Hz, 1 H), 7.81 (d, J = 9.67 Hz, 1 H), 8.26 (d, J = 7.90 Hz, 1 H) ppm. ¹³C NMR (CDCl₃): δ = 56.9, 108.6, 113.6, 124.2, 126.0, 127.7, 128.0, 128.9, 129.8, 133.0, 153.7 ppm. MS (70 eV): m/z = 238 [M⁺ + 2], 236 [M⁺], 223, 221, 195 (100), 193 (100), 127, 114.

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