CuBr/H₂O₂-Mediated Oxidative Coupling of N,N-Dialkylarylamines in ­Water: A Practical Synthesis of Benzidine Derivatives

Abstract

CuBr/H₂O₂ was deployed into mediating the oxidative coupling reaction of N,N-dialkylarylamines in water, which gave benzidine derivatives in an economically and environmentally ­satisfying manner.

oxidative coupling - aqueous reaction - N,N-dialkylaryl­amine - CuBr - H₂O₂

References

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Xi, C.; Jiang, Y.; Yang, X. Tetrahedron. Lett., accepted for publication.

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Representative Procedures.
CuBr (144 mg, 1 mmol) and N,N-diethylaniline 1a (159 µL, 1 mmol) was added into H₂O (3 mL) at 0 °C under N₂. Then, H₂O₂ (1 mL, 10 mmol, 30% aq solution) was added dropwise within 1 min. The reaction mixture was kept at 0 °C for 2 h, then further stirred at 25 °C for 8 h. The reaction mixture was quenched by aq K₂CO₃ solution and the organic residue was extracted with Et₂O (2 × 2 mL). The combined extract was dried over anhyd MgSO₄. The solvent was removed and the residue was chromatographed on an Al₂O₃ column. N,N,N′,N′-tetraethylbenzidine(2a) was isolated using 1:50 EtOAc-petroleum ether mixture as eluent (108 mg, 72%). ¹H NMR (CDCl₃): δ = 7.40 (4 H, d, J = 8.6 Hz), 6.71 (4 H, d, J = 8.6 Hz), 3.35 (8 H, q, J = 7.2 Hz), 1.15 (12 H, t, J = 7.2 Hz). ¹³C NMR (CDCl₃): δ = 146.2, 128.8, 127.0, 112.1, 44.4, 12.6. ESI-MS: m/z = 297 [M + H⁺].

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N , N ′-Dimethyl- N , N ′-dibutylbenzidine ( 2d): white solid, 53% yield. ¹H NMR (CDCl₃): δ = 7.42 (4 H, d, J = 8.9 Hz), 6.72 (4 H, d, J = 8.9 Hz), 3.30 (4 H, br), 2.93 (6 H, s), 1.52-1.58 (4 H, m), 1.29-1.38 (4 H, m), 0.94 (6 H, t, J = 7.2 Hz). ¹³C NMR (CDCl₃): δ = 147.8, 129.1, 126.9, 112.4, 52.6, 38.4, 28.9, 20.4, 14.0. ESI-MS: m/z = 325 [M + H⁺].

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N , N ′-Diisopropyl- N , N ′-dibutylbenzidine ( 2e): white solid, 62% yield. ¹H NMR (CDCl₃): δ = 7.40 (4 H, br), 6.75 (4 H, br), 4.07 (4 H, br), 3.13 (4 H, br), 1.53-1.61 (4 H, m), 1.18 (12 H, d, J = 6.5 Hz), 0.96 (6 H, t, J = 7.2Hz). ¹³C NMR (CDCl₃): δ = 147.1, 129.1, 126.9, 113.3, 48.5, 43.8, 31.6, 20.4, 20.0, 14.0. ESI-MS: m/z = 381 [M + H⁺].

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N , N , N ′, N ′-Tetrabutylbenzidine ( 2f): white solid, 49% yield. ¹H NMR (CDCl₃): δ = 7.40 (4 H, br), 6.69 (4 H, br), 3.28 (8 H, br), 1.54-1.62 (8 H, m), 1.30-1.41 (8 H, m), 0.96 (12 H, t, J = 7.2 Hz). ¹³C NMR (CDCl₃): δ = 146.5, 128.5, 126.9, 111.9, 50.8, 29.5, 20.4, 14.0. ESI-MS: m/z = 409 [M + H⁺].

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Compound 2a: C₂₀H₂₈N₂, crystallized in monoclinic, space group C2/c with cell parameters: a = 16.0904 (19), b = 15.7307 (19), c = 13.9754 (17)ų, α = 90.00, β = 91.843 (2), γ = 90.00°, V = 3535.5 (7) ų, D _c = 1.114 g/cm³, Z = 8. CCDC 269443.

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