Synlett 2013; 24(19): 2586-2590
DOI: 10.1055/s-0033-1339894
letter
© Georg Thieme Verlag Stuttgart · New York

Highly Diastereoselective NHC-Catalyzed [4+3] Annulation of Enals, Alde­hydes and N-Phenyl Urea/Thiourea for the Synthesis of Monocyclic trans-1,3-Diazepanes

Ibadur R. Siddiqui*
a  Laboratory of Green Synthesis, Department of Chemistry, University of Allahabad, Allahabad 211002, India   Email: dr.irsiddiqui@gmail.com
,
Anjali Srivastava
a  Laboratory of Green Synthesis, Department of Chemistry, University of Allahabad, Allahabad 211002, India   Email: dr.irsiddiqui@gmail.com
,
Shayna Shamim
a  Laboratory of Green Synthesis, Department of Chemistry, University of Allahabad, Allahabad 211002, India   Email: dr.irsiddiqui@gmail.com
,
Arjita Srivastava
a  Laboratory of Green Synthesis, Department of Chemistry, University of Allahabad, Allahabad 211002, India   Email: dr.irsiddiqui@gmail.com
,
Shireen,
Malik A. Waseem
a  Laboratory of Green Synthesis, Department of Chemistry, University of Allahabad, Allahabad 211002, India   Email: dr.irsiddiqui@gmail.com
,
Rana K. P. Singh
b  Electro-organic and Green Synthesis Lab, Department of Chemistry, University of Allahabad, Allahabad 211002, India
› Author Affiliations
Further Information

Publication History

Received: 04 July 2013

Accepted after revision: 05 September 2013

Publication Date:
16 October 2013 (online)


Abstract

N-Heterocyclic carbene catalyzed synthesis of 1,3-diazepanes from α,β-unsaturated aldehydes, N-phenyl urea/thiourea and aromatic aldehydes has been developed. The reactive Breslow intermediate, formed by reaction of the enal with the NHC, attacks as a d3 nucleophile at the 1-arylidene-3-arylurea derivative, which is produced by simple reaction of N-phenyl urea/thiourea with an aromatic aldehyde. The resulting intermediate, on subsequent heterocyclization, forms the product with high yield. The reaction proceeded smoothly with high atom economy, producing a new C–C and a new C–N bond in a one-pot operation.

Supporting Information

 
  • References and Notes

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  • 13 Synthesis of 1,3-Diazepanes 5aj; General Procedure: A flame-dried round-bottom flask was charged with imidazolium salt 4b (0.034 g, 0.1 mmol, 10 mol%), α,β-unsaturated aldehyde (1 mmol) and CH2Cl2 (4 mL) under a positive pressure of nitrogen, followed by addition of DBU (0.0152 g, 0.1 mmol, 10 mol%) by using a syringe, and the resulting orange solution was stirred for 30 min at room temperature. To this solution, aromatic aldehyde (1.0 mmol) and N-phenyl urea/thiourea (1.0 mmol) was added by using a syringe and the reaction mixture was stirred for a further 2.5 h (completion of reaction was confirmed by TLC analysis). Subsequently, water (5 mL) was added and the reaction mixture was extracted with EtOAc. The organic phase was dried over anhydrous Na2SO4, filtered, and concentrated under reduced pressure. The crude product was then purified by column chromatography (silica gel; Merck, 60–120 mesh; EtOAc–hexane, 3:22) to afford the pure product. 6-(4-Methoxyphenyl)-7-(4-nitrophenyl)-3-phenyl-1,3-diazepane-2,4-dione (5b);Yellow solid; mp 227–229 °C. 1H NMR (400 MHz, CDCl3): δ = 2.44 (dd, J 5Ha–5Hb = 14.4, J 5Ha–6H = 10.4 Hz, 1 H), 2.69 (dd, J 5Hb–5Ha = 14.4, J 5Hb–6H = 2.4 Hz, 1 H), 3.73 (s, 3 H), 4.05 (ddd, J 6H-5Ha = 10.4, J 6H-7H = 9.4, J 6H-5Hb = 2.4 Hz, 1 H), 5.30 (dd, J 7H-6H = 9.4, J 7H-NH = 2.1 Hz, 1 H), 6.36 (d, J NH-7H = 2.1 Hz, 1 H), 6.69–7.02 (m, 4 H), 7.09–7.64 (m, 5 H), 7.38–8.14 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 171.8, 157.9, 155.4, 146.4, 145.5, 140.9, 135.7, 129.9, 129.0, 127.2, 124.7, 121.8, 121.3, 114.0, 57.6, 55.9, 40.5, 37.4. MS: m/z = 431.15 [M+]. Anal. Calcd for C24H21N3O5: C, 66.81; H, 4.91; N, 9.74. Found: C, 66.86; H, 4.87; N, 9.79. 6,7-Bis(4-nitrophenyl)-3-phenyl-1,3-diazepane-2,4-dione (5d): Yellow solid; mp 231–233 °C. 1H NMR (400 MHz, CDCl3): δ = 2.78 (dd, J 5Ha-5Hb = 14.4, J 5Ha-6H =10.3 Hz, 1 H), 3.09 (dd, J 5Hb-5Ha = 14.4, J 5Hb-6H =2.3 Hz, 1 H), 4.35 (ddd, J 6H-5Ha = 10.3, J 6H-7H = 9.4, J 6H-5Hb = 2.3 Hz, 1 H), 5.63 (dd, J 7H-6H = 9.4, J 7H-NH = 2.3 Hz, 1 H), 6.76 (d, J NH-7H = 2.3 Hz, 1 H), 7.09–7.78 (m, 5 H), 7.39–8.12 (m, 4 H), 7.45–8.24 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 172.4, 156.7, 154.6, 146.9, 146.2, 145.3, 135.9, 130.2, 129.4, 127.6, 124.6, 122.5, 121.8, 120.3, 58.3, 40.7, 38.5. MS: m/z = 446.12 [M+]. Anal. Calcd for C23H18N4O6:C, 61.88; H, 4.06; N, 12.55. Found: C, 61.83; H, 4.10; N, 12.49. 6,7-Bis(4-bromophenyl)-3-phenyl-1,3-diazepane-2,4-dione (5e): Yellow solid; mp 246–248 °C. 1H NMR (400 MHz, CDCl3): δ = 2.73 (dd, J 5Ha-5Hb = 14.4, J 5Ha-6H = 10.3 Hz, 1 H), 2.85 (dd, J 5Hb-5Ha = 14.4, J 5Hb-6H = 2.3 Hz, 1 H), 4.17 (ddd, J 6H-5Ha = 10.3, J 6H-7H = 9.3, J 6H-5Hb = 2.3 Hz, 1 H), 5.35 (dd, J 7H-6H = 9.3, J 7H-NH = 2.3 Hz, 1 H), 6.12 (d, J NH-7H = 2.3 Hz, 1 H), 7.02–7.60 (m, 5 H), 7.05–7.40 (m, 4 H), 7.12–7.44 (m, 4 H). 13C NMR (100 MHz, CDCl3): δ = 171.1, 155.3, 147.2, 136.4, 135.8, 135.3, 131.6, 129.9, 129.0, 128.7, 128.1, 124.9, 121.5, 120.6, 57.6, 39.3, 36.5, 24.3. MS: m/z = 511.97 [M+]. Anal. Calcd for C23H18Br2N2O2: C, 53.72; H, 3.53; N, 5.45. Found: C, 53.76; H, 3.59; N, 5.50.