Synlett 2017; 28(17): 2247-2252
DOI: 10.1055/s-0036-1590306
letter
© Georg Thieme Verlag Stuttgart · New York

Dibenzo[b,e][1,4]diazepin-1-ones and their Ring-Opened Derivatives: Revisited Synthesis, 2D NMR and Crystal Structure

Brahim Cherfaouia, Houria Lakhdaria, b, Norah Bennamane*a, Rachid Ameraouib, Oualid Talhi*b, c, Filipe A. Almeida Pazd, Khaldoun Bacharib, Gilbert Kirsche, Kolli Nejar-Bellaraa, Artur M. S. Silva*c
  • aLaboratoire de Chimie Organique Appliquée, Faculté de Chimie, Université des Sciences et de la Technologie Houari Boumediène, BP 32, El-Alia Bab-Ezzouar, 16111 Alger, Algeria   Email: noraoussaid@yahoo.fr
  • bCentre de Recherche Scientifique et Technique en Analyses Physico-Chimiques CRAPC, BP 384, Bou-Ismail-RP, 42004 Tipaza, Algeria
  • cQOPNA, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal   Email: artur.silva@ua.pt   Email: oualid.talhi@ua.pt
  • dCICECO – Aveiro Institute of Materials, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
  • eLaboratoire Structure et Réactivité des Systèmes Moléculaires Complexes, UMR 7565, Université de Lorraine, Avenue du Général Delestraint, Metz, France
Thanks are due to University of Aveiro and FCT/MEC for financial support to the QOPNA research project (FCT UID/QUI/00062/2013) and to the CICECO-Aveiro Institute of Materials (POCI-01-0145-FEDER-007679; FCT UID/CTM/50011/2013), financed by national funds and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement, and to the Portuguese NMR Network. We would like also to thank FCT/MEC and the General Directorate for Scientific Research and Technological Development – DGRSDT of Algeria and Agence Thématique de Recherche en Sciences et Technologie ATRST for approving the co-financed bilateral project PT-DZ/0005. We further wish to thank CICECO for funding the purchase of the single-crystal X-ray diffractometers.
Further Information

Publication History

Received: 02 May 2017

Accepted after revision: 21 May 2017

Publication Date:
13 July 2017 (eFirst)

Abstract

The synthesis of 2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-ones was revisited and a catalyst-free method was established, by exploring the reactivity of 3-[(2-aminoaryl)amino]dimedones towards carbonylated electrophiles. 2D NMR and single-crystal X-ray diffraction studies were used to characterize the structures unequivocally and to review the mechanism leading to the formation of supposed positional isomers. The action of 3-[(2-aminoaryl)amino]dimedones on chromene-3-carboxylic acid, fumaryl, and oxalyl chloride has led to dibenzo[b,e][1,4]diazepin-1-one ring opening to produce novel Z-configured enaminone and linear diamides.

Supporting Information

 
  • References and Notes

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  • 9 General Procedure for the Synthesis of Compounds 2–7 To a solution of 3-[(2-aminoaryl)amino]dimedone derivative 1ac (0.001 mol) in EtOH (20 mL), the carbonylic derivative (0.001 mol) was added, and the resulting reaction mixture was stirred at r.t. for 4–5 h. In all the cases, a precipitate formed which was filtered-off, dried, and recrystallized from EtOH to give pure products 27. Note: In the case of the synthesis of the diamides 6 and 7, 2 molar equiv of the 3-[(2-aminoaryl)amino]dimedones 1ac (0.002 mol) were used for 1 molar equiv of oxalyl chloride or fumaryl chloride. The reaction also works with an equimolar mixture of the reagent but excess of 1ac remain in the reaction mixture.
  • 10 11-(2-Hydroxyphenyl)-3,3,8-trimethyl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (2b) C22H24N2O2 (colorless crystals, 0.30 g, 87%, mp 175–177 °C). 1H NMR (300 MHz, DMSO-d 6): δ = 1.06 and 1.08 (2 s, 6 H, 3-CH3), 1.99 (s, 3 H, 8-CH3), 2.04 and 2.19 (AB, J = 15.9 Hz, 2 H, H-2), 2.60 (s, 2 H, H-4), 5.28 (d, J = 5.6 Hz, 1 H, 10-NH), 5.89 (d, J = 5.6 Hz, 1 H, H-11), 6.26 (d, J = 1.1 Hz, 1 H, H-9), 6.38 (dd, J = 8.0, 1.1 Hz, 1 H, H-7), 6.39–6.45 (m, 1 H, H-5′), 6.57 (dd, J = 7.5, 1.3 Hz, 1 H, H-6′), 6.71–6.74 (m, 1 H, H-3′), 6.82 (d, J = 8.0 Hz, 1 H, H-6) 6.84–6.91 (m, 1 H, H-4′), 8.76 (s, 1 H, 5-NH), 9.70 (s, 1 H, 2′-OH) ppm. 13C NMR (75 MHz, DMSO-d 6): δ = 20.2 (8-CH3), 27.4 and 28.6 (3-CH3), 31.8 (C-3), 44.2 (C-4), 49.6 (C-2), 52.1 (C-11), 108.9 (C-11a), 114.8 (C-3′), 118.0 (C-5′), 119.9 (C-6), 120.5 and 120.6 (C-7, C-9), 126.6 (C-6′), 127.4 (C-4′), 128.4 (C-5a), 129.9 (C-1′), 131.3 (C-8), 138.3 (C-9a), 155.1 and 155.3 (C-4a, C-2′), 191.8 (C-1, C=O) ppm. HRMS (ESI+): m/z calcd for [C22H24N2O2 + Na]+: 371.1730; found: 371.1721.
  • 11 3,3-Dimethyl-11-(4-oxo-4H-chromen-3-yl)-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (3a) C24H22N2O3 (colorless crystals, 0.22 g, 57%, mp 183–184 °C). 1H NMR (300 MHz, DMSO-d 6): δ = 1.06 and 1.08 (2 s, 6 H, 3-CH3), 2.13 and 2.19 (AB, J = 16.2 Hz, 2 H, H-2), 2.52 and 2.75 (AB, J = 16.2 Hz, 2 H, H-4), 5.46 (d, J = 5.5 Hz, 1 H, 10-NH), 5.78 (d, J = 5.5 Hz, 1 H, H-11), 6.47 (dd, J = 7.6, 1.7 Hz, 1 H, H-9), 6.52–6.70 (m, 2 H, H-7, H-8), 7.01 (dd, J = 7.7, 1.6 Hz, 1 H, H-6), 7.41–7.55 (m, 3 H, H-6′, H-8′, H-2′), 7.74 (ddd, J = 8.6, 7.1, 1.7 Hz, 1 H, H-7′), 8.09 (dd, J = 8.0, 1.7 Hz, 1 H, H-5′), 8.95 (s, 1 H, 5-NH) ppm. 13C NMR (75 MHz, DMSO-d 6): δ = 27.4 and 28.6 (3-CH3), 31.7 (C-3), 44.0 (C-4), 49.3 (C-2), 49.8 (C-11), 106.5 (C-11a), 118.3 (C-8′), 120.4, 120.7 and 120.8 (C-6, C-7, C-9), 123.0 (C-8), 123.1 (C-4a′), 124.8 and 125.0 (C-5′, C-3′), 125.5 (C-6′), 131.0 (C-5a), 134.2 (C-7′), 137.8 (C-9a), 152.5 (C-2′), 155.7 and 155.9 (C-4a, C-8a′), 176.4 (C-4′), 192.1 (C-1) ppm. HRMS (ESI+): m/z calcd for [C24H22N2O3 + H]+: 387.1703; found: 387.1729.
  • 12 (E)-8-Chloro-3,3-dimethyl-11-styryl-2,3,4,5,10,11-hexahydro-1H-dibenzo[b,e][1,4]diazepin-1-one (4a) C23H23ClN2O (beige solid, 0.21 g, 55%, mp 160–161 °C). 1H NMR (300 MHz, DMSO-d 6): δ = 1.00 and 1.05 (2 s, 6 H, 3-CH3), 2.08 and 2.20 (AB, J = 15.9 Hz, 2 H, H-2), 2.51 (s, 2 H, H-4), 5.25 (dd, J = 6.0, 5.9 Hz, 1 H, H-11), 6.03 (dd, J = 15.8, 6.0 Hz, 1 H, H-1′), 6.20 (d, J = 15.8 Hz, 1 H, H-2′), 6.26 (d, J = 5.9 Hz, 1 H, 10-NH), 6.70 (dd, J = 8.6, 2.4 Hz, 1 H, H-7), 6.83 (d, J = 2.4 Hz, 1 H, H-9), 7.01 (d, J = 8.6 Hz, 1 H, H-6), 7.11–7.29 (m, 5 H, H-2′′,6′′, H-3′′,5′′ H-4′′), 8.86 (s, 1 H, 5-NH) ppm. 13C NMR (75 MHz, DMSO-d 6): δ = 27.3 and 28.5 (3-CH3), 31.9 (C-3), 44.0 (C-4), 49.5 (C-2), 53.2 (C-11), 110.3 (C-11a), 119.0 and 119.1 (C-7, C-9), 121.6 (C-6), 126.0 and 126.2 (C-2′′,6′′, C-8), 127.3 (C-4′′), 128.73 and 128.74 (C-3′′,5′′, C-2′), 129.6 (C-5a), 131.8 (C-1′), 136.6 (C-1′′), 140.0 (C-9a), 154.0 (C-4a), 192.2 (C-1) ppm. HRMS (ESI+): m/z calcd for [C23H23ClN2O + H]+: 379.1572; found: 379.1586.
  • 13 (Z)-3-[(2-{[3-(2-Hydroxyphenyl)-3-oxoprop-1-en-1-yl]amino}phenyl)amino]-5,5-dimethylcyclohex-2-en-1-one (5a) C23H24N2O3 (yellow crystals, 0.18 g, 47%, mp 234–235 °C). 1H NMR (300 MHz, DMSO-d 6): δ = 1.09 (2 s, 6 H, 5-CH3), 2.03 (s, 2 H, H-6), 2.53 (s, 2 H, H-4), 4.46 (s, 1 H, H-2), 6.28 (d, J = 8.0 Hz, 1 H, H-2′′), 6.86–6.94 (m, 2 H, H-5′′′, H-3′′′), 7.14–7.26 (m, 2 H, H-5′, H-6′), 7.36–7.49 (m, 2 H, H-4′′′, H-4′), 7.71 (d, J = 8.0 Hz, 1 H, H-3′), 7.90–7.93 (m, 1 H, H-6′′′), 8.10 (dd, J = 12.8, 8.0 Hz, 1 H, H-1′′), 8.74 (s, 1 H, 3-NH), 11.82 (d, J = 12.8 Hz, 1 H, 1′′-NH), 13.12 (s, 1 H, 2′′′-OH) ppm. 13C NMR (75 MHz, DMSO-d 6): δ = 28.1 (5-CH3), 32.3 (C-5), 41.6 (C-4), 50.2 (C-6), 93.2 (C-2′′), 96.6 (C-2), 114.9 (C-3′), 117.8 (C-3′′′), 118.9 (C-5′′′), 119.8 (C-1′′′), 124.3 (C-5′), 126.9 (C-1′), 128.6 and 128.8 (C-4′, C-6′), 129.0 (C-6′′′), 134.9 (C-4′′′), 136.1 (C-2′), 146.5 (C-1′′), 161.6 (C-2′′′), 162.3 (C-3), 193.1 (C-3′′), 195.0 (C-1) ppm. HRMS (ESI+): m/z calcd for [C23H24N2O3 + H]+: 377.1860; found: 377.1871.
  • 14 N 1,N 4-Bis{2-[(5,5-dimethyl-3-oxocyclohex-1-en-1-yl)amino]phenyl}fumaramide (6a) C32H36N4O4 (brown solid, 0.40 g, 73%, mp 219–221 °C). 1H NMR (300 MHz, DMSO-d 6): δ = 1.04 (s, 12 H, 5′′-CH3), 2.28 (s, 4 H, H-4′′), 2.56 (s, 4 H, H-6′′), 5.36 (s, 2 H, H-2′′), 7.30 (s, 2 H, H-2), 7.31–7.35 (m, 4 H, H-3′, H-4′), 7.36–7.49 (m, 2 H, H-5′), 7.84 (d, J = 8.0 Hz, 2H, H-6′), 10.41 (s, 2 H, N1H), 10.70 (s, 2 H, N4H) ppm. 13C NMR (75 MHz, DMSO-d 6): δ = 27.7 (5-CH3), 32.6 (C-5′′), 41.3 (C-6′′), 46.1 (C-4′′), 95.6 (C-2′′), 125.0 (C-6′), 125.9 (C-3′) 127.1 (C-4′), 128.0 (C-5′), 129.5 (C-1′), 132.8 (C-2′), 134.0 (C-2), 162.3 (C-1), 170.6 (C-1′′), 191.2 (C-3′′) ppm. HRMS (ESI+): m/z calcd for [C32H36N4O4 + H]+: 541.2815; found: 541.2776.
  • 15 N 1,N 2-Bis{2-[(5,5-dimethyl-3-oxocyclohex-1-en-1-yl)amino]phenyl}oxalamide (7a) C30H34N4O4 (white solid, 0.42 g, 81%, mp 200–202 °C). 1H NMR (300 MHz, DMSO-d 6): δ = 1.03 (s, 12 H, 5′′-CH3), 2.02 (s, 4 H, H-4′′), 2.39 (s, 4 H, H-6′′), 4.70 (s, 2 H, H-2′′), 7.27–7.40 (m, 6 H, H-3′, H-4′, H-5′), 7.96 (d, J = 7.9 Hz, 2 H, H-6′), 8.58 (s, 2 H, N2H), 9.96 (s, 2 H, N1H) ppm. 13C NMR (75 MHz, DMSO-d 6): δ = 28.0 (5-CH3), 32.5 (C-5′′), 41.6 (C-6′′), 50.1 (C-4′′), 96.8 (C-2′′), 123.2 (C-6′), 126.3 (C-3′) 127.2 (C-4′), 127.6 (C-5′), 130.5 (C-1′), 131.9 (C-2′), 157.6 (C-1′′), 162.3 (C-1), 195.2 (C-3′′) ppm. HRMS (ESI+): m/z calcd for [C30H34N4O4 + Na]+: 537.2472; found: 537.2449.
  • 16 Crystal Data for Compound 2b·EtOH C24H30N2O3, M = 394.50, monoclinic, space group P21/c, Z = 4, a = 9.5603(7) Å, b = 18.5619(12) Å, c = 12.7403(11) Å, β = 111.863(3), V = 2098.3(3) Å3, μ(MoKα) = 0.082 mm–1, D c = 1.249 g cm–3, colorless needle, crystal size of 0.13 × 0.05 × 0.04 mm3. Of a total of 20015 reflections collected, 3827 were independent (R int = 0.0548). Final R1 = 0.0455 [I > 2σ(I)] and wR2 = 0.1092 (all data). Data completeness to θ = 25.24°, 99.6%. CCDC 1531504 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 17 Crystal Data for Compound 3a·5H2O C24H32N2O8, M = 476.51, triclinic, space group Pī, Z = 2, a = 9.3720(6) Å, b = 11.4969(8) Å, c = 13.0910(9) Å, α = 113.510(2), β = 90.028(2), γ = 92.865(2), V = 1291.51(15) Å3, μ(Mo Kα) = 0.092 mm–1, D c = 1.225 g cm–3, colorless plate, crystal size of 0.12 × 0.12 × 0.04 mm3. Of a total of 26256 reflections collected, 6884 were independent (R int = 0.0266). Final R1 = 0.0501 [I > 2σ(I)] and wR2 = 0.1459 (all data). Data completeness to θ = 25.24°, 99.7%. CCDC 1531506 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.
  • 18 Maleki A. Kamalzare M. Tetrahedron Lett. 2014; 55: 6931
  • 19 Crystal Data for Compound 5a·EtOH C25H30N2O4, M = 422.51, monoclinic, space group P21/c, Z = 4, a = 13.8692(12) Å, b = 15.4961(10) Å, c = 11.3368(12) Å, β = 113.249(6), V = 2238.6(4) Å3, μ(MoKα) = 0.085 mm–1, D c = 1.254 g cm–3, yellow plate, crystal size of 0.17 × 0.15 × 0.13 mm3. Of a total of 12149 reflections collected, 4011 were independent (R int = 0.1114). Final R1 = 0.0764 [I > 2σ(I)] and wR2 = 0.2393 (all data). Data completeness to θ = 25.24°, 98.3%. CCDC 1531505 contains the supplementary crystallographic data for this paper. The data can be obtained free of charge from The ­Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/getstructures.