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Synlett 2018; 29(09): 1176-1180
DOI: 10.1055/s-0037-1609347
letter
© Georg Thieme Verlag Stuttgart · New York

Facile Access to 1,5-Benzodiazepines via Amine-Promoted (4+3) Annulations of δ-Acetoxy Allenoates with o-Diaminobenzenes under Mild Conditions

Yi-Fan Wang
a   Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. of China   Email: tongxf@ecust.edu.cn
,
Cheng-Yu He
b   Key Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China   Email: tianping@sioc.ac.cn
,
Longlei Hou
a   Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. of China   Email: tongxf@ecust.edu.cn
,
Ping Tian  *
b   Key Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China   Email: tianping@sioc.ac.cn
c   Innovation Research Institute of Traditional Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, P. R. of China   Email: tianping@shutcm.edu.cn
,
Guo-Qiang Lin
b   Key Laboratory of Synthetic Chemistry of Natural Substances, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, P. R. of China   Email: tianping@sioc.ac.cn
c   Innovation Research Institute of Traditional Chinese Medicine (IRI), Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, P. R. of China   Email: tianping@shutcm.edu.cn
,
Xiaofeng Tong*
a   Key Laboratory for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. of China   Email: tongxf@ecust.edu.cn
› Author AffiliationsFinancial support was generously provided by the 973 Program (2015CB856600), NSFC (21472042, 21772016, 21572251, 21572253), and the Collaborative Innovation Center of Chemical Science and Engineering (Tianjin).
Further Information

Publication History

Received: 20 January 2018

Accepted after revision: 20 February 2018

Publication Date:
23 March 2018 (online)

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Abstract

An amine-promoted (4+3) annulation of δ-acetoxy allenoate with o-diaminobenzene is reported, providing a facile access to 1,5-benzodiazepine. This method features wide reaction scope, mild conditions, and readily available starting materials. The cascade reaction involves aza-Michael addition of o-diaminobenzene to allenoate, elimination of acetate group, and subsequent 1,6-aza-Michael addition.

Key words

1,5-benzodiazepine - annulation - allenoate - diamino­benzene - catalyst-free

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1609347.
  • Supporting Information
 

  • References and Notes

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  • 11 Acetoxy Allenoates 1 and o-Diaminobenzenes 2 To a 10 mL vial were added o-diaminobenzene 2 (0.2 mmol, 1.0 equiv), DIPEA (0.24 mmol, 1.2 equiv), and toluene (2 mL), followed by the slow addition of a solution of δ-acetoxy allenoate 1 (0.24 mmol,1.2 equiv) in toluene (2 mL). The solution was stirred for 12 h at room temperature. The reaction mixture was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography using petroleum ether and ethyl acetate (30:1 to 15:1 v/v) as the eluent to give the corresponding annulations product 3. Ethyl (Z)-2-{4-(4-Isopropylphenyl)-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepin-2-ylidene}acetate (3da) Yellow solid, 86% yield; mp 70–72 °C. 1H NMR (400 MHz, CDCl3): δ = 10.26 (s, 1 H), 7.26 (d, J = 8.2 Hz, 2 H), 7.20 (d, J = 8.2 Hz, 2 H), 6.99–6.93 (m, 2 H), 6.92–6.85 (m, 1 H), 6.76–6.72 (m, 1 H), 4.79 (dd, J = 9.6, 3.8 Hz, 1 H), 4.64 (s, 1 H), 4.23–4.06 (m, 2 H), 3.66 (br s, 1 H),2.90 (hept, J = 6.9 Hz, 1 H), 2.72 (dd, J = 13.8, 9.6 Hz, 1 H), 2.49 (ddd, J = 13.8, 3.8, 1.3 Hz, 1 H), 1.34–1.17 (m, 9 H). 13C NMR (100 MHz, CDCl3): δ = 170.28, 158.84, 148.67, 142.39, 137.83, 129.65, 126.80, 125.98, 124.91, 122.48, 121.35, 120.70, 83.95, 64.84, 58.79, 40.39, 33.76, 23.94, 23.91, 14.53. IR (KBr): 3853, 3336, 2960, 2929, 2870, 1734, 1654, 1616, 1560, 1540, 1507, 1480, 1437, 1364, 1286, 1266, 1246, 1157, 1117, 1095, 1051, 829 cm–1. HRMS (ESI): m/z calcd for C22H27N2O2 +: 351.2067; found: 351.2067 [M + H]+. Ethyl (Z)-2-{4-(4-Cyanophenyl)-1,3,4,5-tetrahydro-2H-benzo[b]­[1,4]diazepin-2-ylidene}acetate (3ha) Yellow solid, 72% yield; mp 60–62 °C. 1H NMR (400 MHz, CDCl3): δ = 10.16 (s, 1 H), 7.66–7.60 (m, 2 H), 7.55–7.50 (m, 2 H), 7.03–6.92 (m, 3 H), 6.83–6.79 (m, 1 H), 5.00–4.92 (m, 1 H), 4.43 (s, 1 H), 4.21–4.04 (m, 2 H), 3.73 (s, 1 H), 2.73 (dd, J = 13.8, 4.7 Hz, 1 H), 2.49 (dd, J = 13.9, 7.0 Hz, 1 H), 1.26 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 169.98, 157.03, 149.30, 137.66, 132.43, 130.48, 127.12, 125.09, 122.49, 122.38, 120.97, 118.63, 111.61, 85.04, 64.57, 58.93, 39.37, 14.44. IR (neat): 3629, 3567, 3343, 3057, 2980, 2931, 2228, 1734, 1653, 1616, 1559, 1541, 1501, 1437, 1405, 1364, 1284, 1267, 1233, 1159, 1118, 1095, 1048, 833 cm–1. HRMS (ESI): m/z calcd for C20H20N3O2 +: 334.1550; found: 334.1550 [M + H]+. Ethyl (Z)-2-{4-Methyl-1,3,4,5-tetrahydro-2H-benzo[b][1,4]dia­zepin-2-ylidene}acetate (3pa) Yellow liquid, 82% yield. 1H NMR (400 MHz, CDCl3): δ = 10.13 (s, 1 H), 6.91–6.75 (m, 3 H), 6.71–6.64 (m, 1 H), 4.61 (s, 1 H), 4.08 (q, J = 7.1 Hz, 2 H), 3.88–3.76 (m, 1 H), 3.17 (br s, 1 H), 2.40 (dd, J = 13.8, 4.4 Hz, 1 H), 2.15 (dd, J = 13.8, 7.0 Hz, 1 H), 1.26–1.17 (m, 6 H).13C NMR (100 MHz, CDCl3): δ = 170.11, 159.16, 137.87, 130.34, 124.67, 122.27, 121.67, 120.90, 84.25, 58.79, 55.83, 39.31, 23.40, 14.54. IR (neat): 3347, 2973, 2927, 1648, 1616, 1588, 1498, 1447, 1364, 1307, 1274, 1232, 1159, 1115, 1095, 1044, 916, 784 cm–1. HRMS (ESI): m/z calcd for C14H19N2O2 +: 247.1441; found: 247.1440 [M + H]+. Ethyl (Z)-2-{4-Benzyl-1,3,4,5-tetrahydro-2H-benzo[b][1,4]dia­zepin-2-ylidene}acetate (3qa) Yellow solid, 85% yield; mp 106–108 °C. 1H NMR (400 MHz, CDCl3): δ = 10.13 (s, 1 H),7.31–7.12 (m, 5 H), 6.89–6.75 (m, 3 H), 6.63–6.56 (m, 1 H), 4.64 (s, 1 H),4.16–4.00 (m, 2 H),3.94–3.82 (m, 1 H), 3.23 (br s, 1 H), 2.82–2.67 (m, 2 H), 2.42 (dd, J = 13.7, 4.7 Hz, 1 H), 2.23 (dd, J = 13.8, 7.2 Hz, 1 H), 1.21 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 170.08, 158.92, 137.89, 137.57, 130.94, 129.27, 128.74, 126.70, 124.69, 122.15, 121.95, 121.33, 84.32, 62.01, 58.80, 43.31, 37.26, 14.52. IR (neat): 3386, 1618, 1588, 1505, 1404, 1365, 1332, 1285, 1262, 1225, 1158, 1123, 1095, 1065, 1039, 1004, 790 cm–1. HRMS (ESI): m/z calcd for C20H23N2O2 +: 323.1754; found: 323.1757 [M + H]+. Ethyl (Z)-2-{1,3,4,5-Tetrahydro-2H-benzo[b][1,4]diazepin-2-ylidene}acetate (3ra) Yellow solid, 45% yield; mp 56–58 °C. 1H NMR (400 MHz, CDCl3): δ = 10.22 (s, 1 H), 6.88–6.79 (m, 2 H), 6.76–6.70 (m, 1 H), 6.67–6.59 (m, 1 H), 4.61 (s, 1 H), 4.08 (q, J = 7.1 Hz, 2 H), 3.60–3.52 (m, 2 H), 3.13 (br s, 1 H), 2.49–2.41 (m, 2 H), 1.21 (t, J = 7.1 Hz, 3 H).13C NMR (100 MHz, CDCl3): δ = 170.34, 160.98, 138.16, 128.87, 124.60, 122.64, 120.60, 119.79, 83.32, 58.81, 48.70, 33.76, 14.55. IR (neat): 3386, 1618, 1588, 1505, 1404, 1365, 1332, 1285, 1262, 1225, 1158, 1123, 1095, 1065, 1039, 1004, 790 cm–1. HRMS (ESI): m/z calcd for C13H17N2O2 +: 233.1285; found: 233.1284 [M + H]+. Ethyl (Z)-2-{7,8-Dimethyl-4-phenyl-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepin-2-ylidene}acetate (3ab) Yellow solid, 70% yield; mp 100–102 °C. 1H NMR (400 MHz, CDCl3): δ = 10.18 (s, 1 H), 7.41–7.22 (m, 5 H), 6.76 (s, 1 H), 6.55 (s, 1 H), 4.80 (dd, J = 9.2, 4.0 Hz, 1 H), 4.58 (s, 1 H), 4.23–4.05 (m, 2 H), 3.56 (br s, 1 H), 2.67 (dd, J = 13.7, 9.2 Hz, 1 H), 2.50 (ddd, J = 13.7, 4.0, 1.1 Hz, 1 H), 2.17 (s, 6 H), 1.27 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 170.29, 158.92, 145.05, 135.43, 133.22, 129.69, 128.73, 127.83, 127.41, 126.05, 123.53, 121.90, 83.54, 65.16, 58.73, 40.37, 19.10, 18.74, 14.55. IR (KBr): 3376, 3276, 3064, 2973, 2906, 2888, 2859, 1654, 1609, 1513, 1482, 1451, 1428, 1365, 1310, 1281, 1242, 1199, 1160, 1129, 1094, 1048, 988, 950, 897 cm–1. HRMS (ESI): m/z calcd for C21H25N2O2 +: 337.1911; found: 337.1910 [M + H]+. Ethyl (Z)-2-{7,8-Dibromo-4-phenyl-1,3,4,5-tetrahydro-2H-benzo[b][1,4]diazepin-2-ylidene}acetate (3ae) Yellow solid, 34% yield; mp 60–62 °C. 1H NMR (400 MHz, CDCl3): δ = 10.17 (s, 1 H), 7.35–7.16 (m, 5 H), 7.13 (s, 1 H), 6.94 (s, 1 H), 4.72 (dd, J = 9.1, 3.6 Hz, 1 H), 4.57 (s, 1 H), 4.16–3.99 (m, 2 H), 3.69 (br s, 1 H), 2.62 (dd, J = 14.0, 9.1 Hz, 1 H), 2.48 (dd, J = 14.0, 3.7 Hz, 1 H), 1.20 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 170.23, 157.97, 143.54, 137.84, 131.84, 130.32, 128.03, 125.10, 122.55, 122.08, 121.74, 121.01, 84.72, 64.57, 58.98, 39.93, 14.61. IR (neat): 3420, 3132, 1717, 1653, 1617, 1559, 1540, 1507, 1490, 1457, 1404, 1300, 1239, 1160, 1066, 1010, 700 cm–1. HRMS (ESI): m/z calcd for C19H19 Br2N2O2 +: 464.9808; found: 464.9806 [M + H]+. Ethyl (Z)-2-{4-Phenyl-1,3,4,5-tetrahydro-2H-naphtho[2,3-b][1,4]diazepin-2-ylidene}acetate (3af) Yellow solid, 51% yield; mp 65–67 °C. 1H NMR (400 MHz, CDCl3): δ = 10.43 (s, 1 H), 7.71–7.59 (m, 2 H), 7.45–7.23 (m, 8 H), 7.16 (s, 1 H), 4.85 (dd, J = 9.1, 4.6 Hz, 1 H), 4.67 (s, 1 H), 4.25–4.11 (m, 2 H), 3.96 (s, 1 H), 2.70 (dd, J = 13.8, 9.1 Hz, 1 H), 2.60 (dd, J = 13.8, 4.6 Hz, 1 H), 1.30 (t, J = 7.1 Hz, 3 H). 13C NMR (100 MHz, CDCl3): δ = 170.24, 158.02, 144.63, 137.89, 132.05, 131.81, 129.99, 128.83, 128.00, 126.73, 126.15, 125.77, 125.25, 124.32, 119.10, 116.58, 85.17, 64.80, 59.00, 39.54, 14.54. IR (KBr): 3629, 3619, 3600, 3587, 3567, 3546, 3528, 3503, 3355, 3056, 2977, 2926, 1734, 1717, 1684, 1654, 1616, 1576, 1559, 1541, 1522, 1507, 1490, 1474, 1457, 1437, 1364, 1286, 1248, 1185, 1156, 1096, 1047, 872, 788 cm–1. HRMS (ESI). m/z calcd for C23H23N2O2 +: 359.1754; found: 359.1753 [M + H]+.