One-flask Conversion of N-Aryliminophosphoranes into N¹, N², N³-Triarylguanidines Promoted by TBAF.

Abstract

N-Aryliminophosphoranes were converted into N¹, N², N³-triarylguanidines in synthetically useful yields by reactions with isocyanates followed by treatment of resulting N¹, N²-diarylcarbodiimide with aromatic amines in the presence of TBAF.

iminophosphoranes - isocyanates - carbodiimides guanidines - tetrabutylammonium fluoride

References

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23

Typical experimental procedure. To a mixture of the appropriate iminophosphorane 1 (1.16 mmol), anhydrous MgSO₄ (2 g) and dry THF (5 mL) was added an equimolar amount of the adequate isocyanate 2 under N₂. The reaction mixture was stirred at r.t. for 1 h. Afterwards, the aromatic amine 4 (1.74 mmol) and 1 M TBAF in THF (1.8 mL, 1.8 mmol) were added and stirring was continued for 10 min. The crude was poured into Na₂HPO₄ buffer (pH = 7, 15 mL) and extracted with EtOAc (3 ¥ 25 mL). The combined organic layers were dried (MgSO₄), filtered, and concentrated to dryness. The crude solid was chromato-graphed on a silica gel column using hexane-EtOAc (2:1) as eluent to give 5.

24

Compound 5a: mp 141-142 °C (white prisms); ¹H NMR (300 MHz, DMSO) d 2.19 (s, 6 H, CH₃), 6.67 (m, 1 H), 6.92 (m, 6 H), 7.11 (m, 4 H), 7.42 (d, 1 H, J = 7.8 Hz) 8.15 (s, 2 H, NH). ¹³C NMR (50.32 MHz, DMSO) d 20.32 (2 ¥ CH₃), 117.23 (q), 119.31, 121.90, 123.01, 127.68, 128.82 (2 ¥ CH) 129.98, 132.17, 138.65 (q), 146.03 (q), 147.81 (q). MS (EI, 70 eV); m/z (%): 396 (M⁺ + 2, 10), 394 (M⁺, 16), 393 (37), 314 (28), 288 (37), 222 (56), 107 (100), 91 (44). C₂₀H₂₀BrN₃ (382.305) calcd C, 62.83; H, 5.27; N, 10.98. Found C, 62.70; H, 5.35; N, 10.72.
Compound 5b: mp 115-116 °C (brown prisms); ¹H NMR (300 MHz, DMSO) d 2.18 (s, 3 H, CH₃), 3.66 (s, 3 H, CH₃O), 6.69 (m, 1 H), 6.77 (d, 2 H, J = 9 Hz), 6.87 (m, 1 H), 6.96 (d, 2 H, J = 8.4 Hz), 7.05 (m, 1 H), 7.14 (m, 2 H,) 7.41 (d, 1 H, J = 7.8 Hz), 8.05 (s, 2 H, 2 ¥ NH). ¹³C NMR (50.32 MHz, DMSO) 20.30 (CH₃), 55.13 (CH₃O), 113.71 (CH), 117.33 (q), 119.33, 121.33, 121.83, 123.16, 127.70, 128.82, 129.90 (q), 132.15, 134.01 (q), 138.6 (q), 146.36 (q), 148.24 (q), 154.32 (q). MS (EI, 70 eV); m/z (%): 412 (M⁺ + 2, 6), 410 (M⁺, 8), 330 (20), 304 (17), 302 (18), 284 (14), 287 (17), 238 (28), 223 (27), 1237 (100), 91 (33), 77 (17). C₂₀H₂₀BrN₃O (398.304) calcd C, 60.31; H, 5.06; N, 10.55. Found C, 60.50; H, 4.90; N, 10.79.
Compound 5c: mp 131-132 °C (white prisms); ¹H NMR (300 MHz, CDC₃) d 2.18 (s, 3 H, CH₃), 6.69 (m, 1 H), 6.75 (d, 1 H), 6.75 (d, 2 H, J = 8.2 Hz), 7.07 (m, 1 H), 7.12 (d, 2 H, J = 8.4 Hz), 7.18 (d, 2 H J = 9 Hz), 7.43 (d, 2 H) 8.55 (s, 2 H) ¹³C NMR (50.32 MHz, DMSO) d 20.30 (CH₃), 117.07 (q), 119.47, 120.48, 122.28 123.12, 127.76, 128.18, 128.88, 130.27 (q), 132.23 (q), 139.2 (q), 145,7 (q). MS (EI, 70 eV); m/z (%): 418 (M⁺ + 4, 7), 416 (M⁺ + 2, 28), 414 (M⁺, 50), 336 (26), 334 (47), 332 (8), 289 (31), 287 (35). 244 (26), 242 (58), 167 (27), 127 (36), 106 (100), 91 (39), 77 (38). C₁₉H₁₇BrClN₃ (402.723) calcd C, 56.67; H, 4.25; N, 10.43. Found C, 56.49; H, 4.19; N, 10.65.
Compound 5d: mp 154-155 °C (yellow prisms); ¹H NMR (300 MHz, CDCl₃) d 2.38 (s, 3 H, CH₃), 5.80 (s, 2 H), 6.91 (m, 1 H), 7.39 (m, 9 H), 8.16 (d, 2 H, J = 9.1 Hz), 8.16 (d, 2 H, J = 9.1 Hz). ¹³C NMR (50.32 MHz, CDCl₃) d 20.88 (CH₃), 116.24 (q), 120.44, 122.95, 124.19, 124.35, 125.18, 128.38, 130.34, 132.95, 134.94 (q), 135.85 (q), 141.11 (q), 142.07 (q), 145.04 (q), 150.77 (q). MS (EI, 70 eV); m/z (%):427 (M⁺ + 2, 12), 425(M⁺, 21), 345 (50), 286 (34), 253 (37), 171 (51), 106 (100), 90 (51). C₁₉H₁₇BrN₄ O₂ (413.274) calcd C, 55.22; H, 4.15; N, 13.56. Found C, 55.44; H, 4.28; N, 13.35.
Compound 5e: mp 146-147 °C (yellow prisms); ¹H NMR (300 MHz, DMSO) d 2.18 (s, 3 H, CH₃), 6.69 (m, 1 H), 6.75 (d,1 H), 6.71 (d, 2 H, J = 8.2 Hz), 7.07 (m, 1 H), 7.12 (d, 2 H, J = 8.4 Hz), 7.18 (d, 2 H, J = 9 Hz), 7.25 (d, 2 H, J = 9 Hz), 7.43 (d, 2 H), 8.55 (s, 2 H). ¹³C NMR (50.32 MHz, DMSO) d 20.30 (CH₃), 117.07 (q), 119.47, 120.48, 122.28, 123.12, 127.76, 128.18, 128.88, 130.27 (q), 128.88, 132.23, 139.2 (q), 145.7 (q). (q). MS (EI, 70 eV); m/z (%): 412 (M⁺ + 2, 24), 410 (M⁺, 24), 366 (31), 354 (35), 349 (39), 289 (98), 272 (97), 210 (96), 196 (47), 170 (100), 154 (49), 148 (51), 104 (66), 77 (33). C₁₇H₁₅BrN₄O₂ (399.25) calcd C, 54.15; H, 4.15; N, 13.56. Found C, 54.09; H, 4.01, N, 13.68.
Compound 5f: mp 201-202 °C (white prisms); ¹H NMR (300 MHz, DMSO) d 2.18 (s, 3 H, CH₃), 6.69 (m, 1 H), 6.75 (d, 1 H), 6.75 (d, 2 H, J = 8.2 Hz), 7.07 (m, 1 H), 7.12 (d, 2 H, J = 8.4 Hz), 7.18 (d, 2 H J = 9 Hz), 7.43 (d, 2 H), 8.5 5 (s, 2 H) ¹³C NMR (50.32 MHz, DMSO) d 20.30 (CH₃), 117.07 (q), 119.47, 120.48, 122.28 123.12, 127.76, 128.18, 128.88, 130.27 (q), 132.23 (q), 139.2 (q), 145,7 (q). MS (EI, 70 eV); m/z (%): 303 (M⁺, 87), 210 (51), 209 (89), 197 (100), 107 (61), 77 (95), C₁₈H₁₇N₅ (303.362) calcd C, 71.27; H, 17.13; N, 23.08. Found C, 71.05; H, 16.92; N, 22.95.

25 Sharma GVM. Reddy VG. Chander AS. Reddy KR. Tetrahedron: Asymmetry  2002,  13:  21