Base-Mediated Synthesis of Imines and Amines from N-Phenylureas and Alcohols

Abstract

A new base-mediated protocol has been developed for the synthesis of imines and amines from N-phenylureas and alcohols under normal air. From the synthetic point of view, the protocol can be considered as an efficient alternative to conventional methods for the synthesis of imines and amines in moderate to excellent yields.

Key words

imines - amines - oxidations - alcohols - ureas

• References and Notes

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• 21 Imines 3a–s; General Procedure A mixture of the appropriate N-arylurea (1 mmol), arylmethanol (3 mmol), and KOH (1.5 mmol) was stirred at 135 °C under a normal air atmosphere in a sealed 20-mL Schlenk tube for 24 h. When the reaction was complete (GC), EtOAc (3 mL) and H₂O (3 mL) were added and the mixture was stirred vigorously. The organic layer was separated, and the aqueous layer was extracted with EtOAc (2 × 3 mL). The organic layers were combined, dried (Na₂SO₄), and concentrated under reduced pressure. The crude product was purified by column chromatography (basic alumina saturated with Et₃N, PE). The identity of the compound was confirmed by various spectroscopic techniques, and its purity was determined by GC-MS analysis. N-Benzylideneaniline (3a) ¹⁸ Brown oil; yield: 172 mg (95%). ¹H NMR (400 MHz, CDCl₃): δ = 8.45 (s, 1 H), 7.91–7.88 (m, 2 H), 7.47–7.37 (m, 5 H), 7.24–7.20 (m, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 160.4, 152.1, 136.2, 131.4, 129.1, 128.8, 128.7, 125.9, 120.9. GC-MS (EI, 70 eV): m/z (%) = 181 (90) [M]⁺, 180 (100), 152 (5), 104 (10), 77 (60), 51 (15), 39 (5). N-(4-Methoxybenzylidene)aniline (3c) ²⁸ White solid; yield: 198 mg (94%); mp 63–67 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.37 (s, 1 H), 7.84 (d, J = 8.8 Hz, 2 H), 7.37 (t, J = 7.5 Hz, 2 H), 7.20–7.12 (m, 3 H), 6.97 (d, J = 8.8 Hz, 2 H), 3.85 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 162.2, 159.7, 152.4, 130.5, 129.1, 125.5, 120.9, 114.2, 55.4. GC–MS (EI, 70 eV): m/z (%) = 211 (20) [M]⁺, 210 (100), 195 (6), 167 (10), 77 (42), 51 (15). N-(2-Chlorobenzylidene)aniline (3f) ¹⁸ Brown oil; yield: 148 mg (69%). ¹H NMR (400 MHz, CDCl₃): δ = 8.91 (s, 1 H), 8.25–8.23 (m, 1 H), 7.42–7.32 (m, 5 H), 7.27–7.23 (m, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 156.9, 151.8, 136.1, 133.6, 132.4, 129.9, 129.3, 128.6, 127.2, 126.4, 121.1. GC–MS (EI, 70 eV): m/z (%) = 217 (26) [M + 2]⁺, 215 (80) [M]⁺, 180 (37), 152 (7), 112 (7), 104 (24), 89 (7), 77 (100), 63 (8), 51 (41). N-(3-Chlorobenzylidene)aniline (3g) ¹⁸ Brown oil; yield: 172 mg (80%). ¹H NMR (400 MHz, CDCl₃): δ = 8.39 (s, 1 H), 7.93 (s, 1 H), 7.73 (d, J = 7.6 Hz, 1 H), 7.45–7.37 (m, 4 H), 7.25–7.20 (m, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 158.6, 151.5, 137.9, 134.9, 131.2, 130.4, 129.2, 128.3, 127.1, 126.3, 120.8. GC–MS (EI, 70 eV): m/z (%) = 217 (26) [M + 2]⁺, 215 (78) [M]⁺, 180 (4), 151 (5), 112 (4), 104 (30), 89 (13), 77 (100), 63 (8), 51 (38). N-(4-Chlorobenzylidene)aniline (3h) ¹⁸ White solid; yield: 187 mg (87%); mp 75–77 °C. ¹H NMR (400 MHz, CDCl₃): δ = 8.40 (s, 1 H), 7.83 (d, J = 8.4 Hz, 2 H), 7.43 (d, J = 8.4 Hz, 2 H), 7.41–7.37 (m, 2 H), 7.26–7.19 (m, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 158.8, 151.7, 137.3, 134.7, 130.0, 129.2, 129.0, 126.2, 120.8. GC–MS (EI, 70 eV): m/z (%) = 217 (28) [M + 2]⁺, 215 (40) [M]⁺, 178 (4), 152 (5), 138 (2), 104 (17), 89 (13), 77 (100), 63 (8), 51 (38). N-(4-Fluorobenzylidene)aniline (3i) ¹⁸ Brown oil; yield: 163 mg (82%). ¹H NMR (400 MHz, CDCl₃): δ = 8.40 (s, 1 H), 7.91–7.87 (m, 2 H), 7.40–7.37 (m, 2 H), 7.25–7.12 (m, 5 H). ¹³C NMR (100 MHz, CDCl₃): δ = 164.7 (d, J _C–F = 251 Hz), 158.8, 151.8, 132.6 (d, J _C–F = 3 Hz), 130.8 (d, J _C–F = 8 Hz), 129.2, 126.1, 120.8, 115.9 (d, J _C–F = 22 Hz). GC–MS (EI, 70 eV): m/z (%) = 199 (93) [M]⁺, 198 (100), 169 (1), 107 (6), 104 (13), 99 (3), 96 (6), 95 (3), 89 (7), 85 (3), 78 (7), 77 (79), 51 (27), 50 (5).
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• 23 Amines 4a–m; General Procedure A 20 mL Schlenk tube was charged with the appropriate N-arylurea (1 mmol), arylmethanol (5 mmol), and KOt-Bu (3.5 mmol). The mixture was then heated at 135 °C under normal atmospheric air for 24 h while the progress of reaction was monitored by GC and/or TLC. When the reaction was complete, H₂O (3 mL) and EtOAc (3 mL) were added and the mixture was stirred vigorously. The organic layer was separated, and the aqueous layer was extracted with EtOAc (2 × 3 mL). The organic layers were combined, dried (Na₂SO₄), and concentrated under reduced pressure. The crude product was purified by column chromatography [silica gel (100–200 mesh), PE–EtOAc] to give the corresponding pure product. The product was characterized by various spectroscopic techniques and its purity was confirmed by GC–MS analysis.
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