A Novel Efficient Three-Component One-Pot Synthesis of 1,3-Diazabicyclo[3.1.0]hex-3-ene System under Microwave Irradiation

Abstract

Bridgehead aziridines 3 were synthesized in high yields and excellent diastereocontrol by a three-component reaction of an aldehyde, phenacyl chloride and ammonium acetate in acetic acid using microwave irradiation.

Key words

multicomponent - microwave - bicyclic aziridine - dia­stereocontrol

References

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Microwave Irradiation.
A mixture of phenacyl chloride 1 (463.7 mg, 3 mmol), aldehyde 2 (6 mmol), ammonium acetate (1.55 g, 20 mmol) and glacial acetic acid (10 mL) in n-PrOH (20 mL) in the presence of molecular sieves (4 Å) was irradiated for 5-10 min in a self-tunable CEM microwave synthesizer at 90 °C. After cooling the reaction to r.t., the solvent was removed under vacuum and the residue was crystallized from EtOH to give 3 as colorless crystals.

7

Conventional heating.
As above procedure, but absolute EtOH was used as solvent and the reaction mixture was refluxed for 2-3 h.

8

Selected data.
Compound 3a: mp 155-156 °C (lit.^5a mp 153-154 °C). ΙR (nujol): 1597, 1569, 1046 cm^-1. ¹H NMR (CDCl₃): δ = 2.72 (d, J = 2.2 Hz, HC-6), 3.74 (dd, J = 2.2 and 2.9 Hz, HC-5), 6.22 (d, J = 2.9 Hz, HC-2), 7.30-8.01 (m, arom., 15 H). ¹³C NMR (CDCl₃): δ = 49.0 (C-5), 56.4 (C-6), 97.4 (C-2), 170.4 (C-3). Anal. Calcd for C₂₂H₁₈N₂: C, 85.13; H, 5.85; N, 9.03. Found: C, 85.31; H, 5.94; N, 9.14.
Compound 3b: mp 134-135 °C. ΙR (nujol): 1601, 1578, 1050 cm^-1. ¹H NMR (CDCl₃): δ = 2.43 (s, 3 H), 2.65 (s, 3 H), 2.85 (d, J = 2.1 Hz, HC-6), 3.65 (dd, J = 2.1 and 3.0 Hz, HC-5), 6.35 (d, J = 3.0 Hz, HC-2), 7.18-8.05 (m, arom., 13 H). ¹³C NMR (CDCl₃): δ = 47.8 (C-5), 56.8 (C-6), 94.5 (C-2), 171.2 (C-3). Anal. Calcd. for C₂₄H₂₂N₂: C, 85.17; H, 6.55; N, 8.28. Found: C, 85.40; H, 6.73; N, 8.11.
Compound 3c: mp 152-153 °C. ΙR (nujol): 1599, 1573, 1048 cm^-1. ¹H NMR (CDCl₃): δ = 2.43 (s, 3 H), 2.46 (s, 3 H), 2.72 (d, J = 1.8 Hz, HC-6), 3.78 (dd, J = 1.8 and 2.2 Hz, HC-5), 6.24 (d, J = 2.2 Hz, HC-2), 7.16-8.08 (m, arom., 13 H). ¹³C NMR (CDCl₃): δ = 49.3 (C-5), 56.6 (C-6), 99.1 (C-2), 170.4 (C-3). Anal. Calcd for C₂₄H₂₂N₂: C, 85.17; H, 6.55; N, 8.28. Found C, 85.32; H, 6.69; N, 8.38.
Compound 3d: mp 148-149 °C. ΙR (nujol): 1599, 1580, 1040 cm^-1. ¹H NMR (CDCl₃): δ = 2.66 (d, J = 1.9 Hz, HC-6), 3.70 (dd, J = 1.9 and 2.4 Hz, HC-5), 3.77 (s, 3 H), 3.79 (s, 3 H), 6.17 (d, J = 2.4 Hz, HC-2), 6.82-7.98 (m, arom., 13 H). ¹³C NMR (CDCl₃): δ = 49.0 (C-5), 53.8 (C-6), 97.3 (C-2), 170.4 (C-3). Anal. Calcd for C₂₄H₂₂N₂O₂: C, 77.81; H, 5.99; N, 7.56. Found: C, 77.98; H, 6.08; N, 7.69.
Compound 3e: mp 118-119 °C. ΙR (nujol): 1596, 1572, 1048 cm^-1. ¹H NMR (CDCl₃): δ = 2.62 (d, J = 1.8 Hz, HC-6), 3.65 (dd, J = 1.8 and 2.7 Hz, HC-5), 6.12 (d, J = 2.7 Hz, HC-2), 7.23-7.95 (m, arom., 13 H). ¹³C NMR (CDCl₃): δ = 48.2 (C-5), 56.5 (C-6), 96.7 (C-2), 170.5 (C-3). Anal. Calcd for C₂₂H₁₆Cl₂N₂: C, 69.67; H, 4.25; N, 7.39. Found: C, 69.80; H, 4.32; N, 7.21.
Compound 3f: mp 135-136 °C. ΙR (nujol): 1600, 1581, 1049 cm^-1. ¹H NMR (CDCl₃): δ = 2.29 (s, 3 H), 2.42 (s, 3 H), 2.69 (d, J = 2.0 Hz, HC-6), 3.65 (dd, J = 2.0 and 2.9 Hz, HC-5), 6.21 (d, J = 2.9 Hz, HC-2), 7.10-8.01 (m, arom., 13 H). ¹³C NMR (CDCl₃): δ = 48.5 (C-5), 56.5 (C-6), 97.1 (C-2), 170.9 (C-3). Anal. Calcd for C₂₄H₂₂N₂: C, 85.17; H, 6.55; N, 8.28. Found: C, 85.01; H, 6.42; N, 8.39.
Compound 3g: mp 68-69 °C. ΙR (nujol): 1610, 1576, 1041 cm^-1. ¹H NMR (CDCl₃): δ = 0.99 (s, 9 H), 1.02 (s, 9 H), 1.18 (d, J = 2.1 Hz, HC-6), 3.22 (dd, J = 2.1 and 3.3 Hz, HC-5), 4.49 (d, J = 3.2 Hz, HC-2), 7.39-7.51 (m, arom., 3 H), 7.85-7.88 (m, arom., 2 H). ¹³C NMR (CDCl₃): δ = 49.8 (C-5), 56.2 (C-6), 104.3 (C-2), 170.2 (C-3). Anal. Calcd. for C₁₈H₂₆N₂: C, 79.95; H, 9.69; N, 10.36. Found: C, 79.78; H, 9.60; N, 10.49.

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X-ray data to be submitted to J. Mol. Struct.