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Synlett 2016; 27(03): 375-378
DOI: 10.1055/s-0035-1560904
letter
© Georg Thieme Verlag Stuttgart · New York

A Versatile One-Pot Strategy for the Synthesis of [1,4]Thiazepino[5,4-a]isoquinolines Containing Intramolecular Hydrogen Bonds

Abdolali Alizadeh*
a   Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Email: aalizadeh@modares.ac.ir   Email: abdol_alizad@yahoo.com
,
Fahimeh Bayat
a   Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Email: aalizadeh@modares.ac.ir   Email: abdol_alizad@yahoo.com
,
Zhe Zhu
b   Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, P. R. of China
› Author Affiliations
Further Information

Publication History

Received: 27 August 2015

Accepted after revision: 06 October 2015

Publication Date:
19 November 2015 (online)

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Abstract

A simple and efficient one-pot method is described for the construction of [1,4]thiazepino[5,4-a]isoquinolines containing intramolecular hydrogen bonds by a sequential four-component domino reaction of isoquinoline, a 2-bromoacetophenone, an aryl isothiocyanate, and dimethyl acetylenedicarboxylate.

Key words

heterocycles - polycycles - isoquinolines - hydrogen bonds - domino reactions - multicomponent reactions
 

  • References and Notes

  • 3 Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL. Neuropsychopharmacology 2008; 33: 2303
    CrossrefSearch in Google Scholar
  • 4 Sulman FG, Pfeifer Y, Superstine E. Arzneim.-Forsch. 1981; 31: 109
    Search in Google Scholar
  • 5 Kaur H, Kumar S, Chaudhary A, Kumar A. Arabian J. Chem. 2012; 5: 271
    CrossrefSearch in Google Scholar
  • 6 Wehrens XH, Lehnart SE, Reiken SR, Deng S.-X, Vest JA, Cervantes D, Coromilas J, Landry DW, Marks AR. Science 2004; 304: 292
    CrossrefSearch in Google Scholar
  • 7 Ruiz A, Alberdi E, Matute C. Cell Death Dis. 2014; 5: e1156
    CrossrefSearch in Google Scholar
  • 8 Wang L. Comput. Biol. Med. 2009; 39: 355
    CrossrefSearch in Google Scholar
  • 9 Glaser R, Sklarz B. J. Chem. Soc., Perkin Trans. 2 1989; 1031
  • 11 Goren L, Pappo D, Goldberg I, Kashman Y. Tetrahedron Lett. 2009; 50: 1048
    CrossrefSearch in Google Scholar
  • 13 Hopkin MD, Baxendale IR, Ley SV. Synthesis 2008; 1688
    Thieme Connect
  • 14 Maity A, Chakraborty D, Hazra A, Bharitkar YP, Kundu S, Maulik PR, Mondal NB. Tetrahedron Lett. 2014; 55: 3059
    CrossrefSearch in Google Scholar
  • 16 [1,4]Thiazepino[5,4-a]isoquinolines 3a–g; General Procedure A mixture of the appropriate 2-bromoacetophenone 1 (1 mmol) and isoquinoline (1 mmol) in MeCN (2 mL) was stirred at r.t. for 30 min. Aryl isothiocyanate 2 (1 mmol) was added, followed by dropwise addition of Et3N (1 mmol), and the mixture was stirred at r.t. for 20 min. Finally, DMAD (1 mmol) was added dropwise to the mixture. When the reaction was complete (2 h, TLC), the solvent was removed and the residue was purified by flash column chromatography [silica gel, hexane–EtOAc (1:6)]. Dimethyl 4-Anilino-5-benzoyl-12bH-[1,4]thiazepino[5,4-a]isoquinoline-1,2-dicarboxylate (3a) Yellow–orange crystals; yield: 0.39 g (75%); mp 179–180 °C; IR (KBr): 3445 (N–H), 1732 (C=O), 1586 and 1528 (Ar), 1375 (C–N), 1238 (C–O) cm–1. 1H NMR (300 MHz, DMSO-d 6): δ = 3.36 (s, 3 H, OCH3), 3.63 (s, 3 H, OCH3), 5.53 (s, 1 H, CH), 5.62 (d, 3 J HH = 7.4 Hz, 1 H, CH8 of isoquinoline), 6.62 (d, 3 J HH = 7.4 Hz, 1 H, CH7 of isoquinoline), 6.71 (d, 3 J HH = 7.6 Hz, 1 H, CH of Ar), 6.93–6.95 (m, 2 H, 2 × CH of Ar), 7.07–7.20 (m, 4 H, 4 × CH of Ar), 7.25–7.33 (m, 5 H, 5 × CH of Ar), 7.51 (d, 3 J HH = 7.6 Hz, 2 H, 2 × CH of Ar), 11.30 (s, 1 H, NH). 13C NMR (75 MHz, DMSO-d 6): δ = 52.2 (OCH3), 53.5 (OCH3), 60.3 (CH), 101.2 (CH8), 121.8 (C1), 122.1 (CH of Ar), 122.9 (CH of Ar), 123.9 (C5), 124.4 (C2), 124.7 (CH of Ar), 126.3 (CH of Ar), 126.6 (2 × CH of Ph), 127.4 (CH of Ph), 127.7 (2 × CH of Ph), 128.3 (2 × CH of Ph), 128.9 (2 × CH of Ph), 129.0 (CH of Ar), 132.2 (C8a), 137.0 (CH7), 138.7 (C4), 139.1 (Cipso –CO), 144.1 (C ipso –N), 162.0 (C12a), 164.2 (CO2Me), 165.3 (CO2Me), 187.5 (C=O). MS (EI, 70 eV): m/z (%) = 395 (42), 337 (24), 303 (16), 275 (23), 172 (14), 129 (71), 105 (92), 77 (100). Anal. Calcd for C30H24N2O5S (524.59): C, 68.69; H, 4.61; N, 5.34. Found: C, 68.62; H, 4.66; N, 5.44. Crystal data for 3a: C30H23N2O5S: MW = 523.56, monoclinic, P1, a = 9.5067(5), b = 21.4933(12), c = 12.8134(6) Å, β = 102.389(1), V = 2557.2(2) Å3, Z = 2, D calcd = 1.360 mg/m3, F (000) = 1092; crystal dimensions: 0.34 × 0.27 × 0.15 mm; radiation, Mo Kα (λ = 0.71073Å), 1.89 ≤ 2θ ≤ 25.10. Intensity data were collected at 295(2) K with a Bruker APEX area-detector diffractometer by employing the ω/2θ scanning technique in the range –11 ≤ h ≤ 11, –25 ≤ k ≤ 25, –15 ≤ l ≤ 15. The structure was solved by a direct method; all nonhydrogen atoms were positioned, and anisotropic thermal parameters refined from 3615 observed reflections with R(into) = 0.0565 by a full-matrix least-squares technique converged to R = 0.0413 and R aw = 0.1177 [I > 2σ(I)]. Dimethyl 5-Benzoyl-4-[(3-bromophenyl)amino]-12bH-[1,4]thiazepino[5,4-a]isoquinoline-1,2-dicarboxylate (3b) Orange crystals; yield: 0.44 g (73%); mp 141–144 °C. IR (KBr): 3444 (N–H), 1728 (C=O), 1611 and 1549 (Ar), 1357 (C–N), 1239 (C–O) cm–1. 1H NMR (300 MHz, CDCl3): δ =3.37 (s, 3 H, OCH3), 3.70 (s, 3 H, OCH3), 5.34 (s, 1 H, CH), 5.73 (d, 3 J HH = 7.2 Hz, 1 H, CH8 of isoquinoline), 6.43 (d, 3 J HH = 7.2 Hz, 1 H, CH7 of isoquinoline), 6.67 (d, 3 J HH = 7.5 Hz, 1 H, CH of Ar), 6.95 (t, 3 J HH = 7.5 Hz, 1 H, CH of Ar), 6.98 (d, 3 J HH = 7.5 Hz, 1 H, CH of Ar), 7.12 (d, 3 J HH = 7.8 Hz, 1 H, CH of Ar), 7.16 (t, 3 J HH = 8.7 Hz, 2 H, 2 × CH of Ar), 7.25–7.30 (m, 3 H, 3 × CH of Ar), 7.41 (d, 3 J HH = 8.4 Hz, 1 H, CH of Ar), 7.45 (d, 4 J HH = 1.5 Hz, 1 H, CH of Ar), 7.66 (d, 3 J HH = 7.8 Hz, 2 H, 2× CH of Ar), 10.00 (br s, 1 H, NH). 13C NMR (75 MHz, DMSO-d 6): δ = 52.4 (OCH3), 53.4 (OCH3), 61.8 (CH), 102.2 (CH8), 122.5 (C1), 122.7 (C5), 122.8 (C2), 123.3 (CH of Ar), 123.7 (CH of Ar), 123.8 (CH of Ar), 125.0 (CH of Ar), 126.3 (CH of Ar), 127.8 (2 × CH meta of Ph), 127.9 (2 × CH ortho of Ph), 128.2 (CH para of Ph), 128.4 (CH of Ar), 129.5 (CH of Ar), 130.3 (CH), 130.9 (CH of Ar), 132.3 (C8a), 136.3 (CH7), 138.3 (C4), 139.4 (Cipso –CO), 145.7 (C ipso –N), 161.7 (C12a), 164.0 (CO2Me), 166.3 (CO2Me), 190.3 (C=O). MS (EI, 70 eV): m/z (%) = 473 (16), 415 (18), 374 (17), 220 (32), 129 (96), 105 (100), 77 (100). Anal. Calcd for C30H23BrN2O5S (603.48): C, 59.71; H, 3.84; N, 4.64. Found: C, 59.65; H, 3.27; N, 4.70. Dimethyl 5-Benzoyl-4-[(2,4-dichlorophenyl)amino]-12bH-[1,4]thiazepino[5,4-a]isoquinoline-1,2-dicarboxylate (3c) Orange crystals; yield: 0.40 g (68%); mp 172–174 °C. IR (KBr): 3445 (N–H), 1727 (C=O), 1617 and 1537 (Ar), 1363 (C–N), 1241 (C–O) cm–1. 1H NMR (300 MHz, CDCl3): δ = 3.34 (s, 3 H, OCH3), 3.61 (s, 3 H, OCH3), 5.38 (s, 1 H, CH), 5.73 (d, 3 J HH = 7.2 Hz, 1 H, CH8 of isoquinoline), 6.43 (d, 3 J HH = 7.2 Hz, 1 H, CH7 of isoquinoline), 6.70 (d, 3 J HH = 7.5 Hz, 1 H, CH of Ar), 6.97 (t, 3 J HH = 8.4 Hz, 1 H, CH of Ar), 6.98 (d, 3 J HH = 7.8 Hz, 1 H, CH of Ar), 7.11–7.19 (m, 3 H, 3 × CH of Ar), 7.25–7.31 (m, 3 H, 3 × CH of Ar), 7.49 (s, 1 H, CH of Ar), 7.68 (d, 3 J HH = 7.5 Hz, 2 H, 2 × CH of Ar), 10.00 (br s, 1 H, NH). 13C NMR (75 MHz, CDCl3): δ =52.4 (OCH3), 53.3 (OCH3), 61.7 (CH), 102.4 (CH8 of isoquinoline), 123.0 (C1), 123.3 (CH of Ar), 123.5 (C5), 123.7 (C2), 125.1 (CH of Ar), 126.4 (CH of Ar), 127.4 (CH of Ar), 127.6 (CH of Ar), 127.8 (2 × CH of Ar), 128.0 (2 × CH of Ar), 128.5 (CH of Ar), 129.9 (CH of Ar), 130.3 (C ipso –Cl), 131.0 (CH of Ar), 132.0 (C8a), 132.4 (C ipso –Cl), 134.8 (C4), 136.0 (CH7), 137.9 (C ipso –CO), 145.7 (C ipso –N), 161.1 (C12a), 163.9 (CO2Me), 166.2 (CO2Me), 189.9 (C=O); MS (EI, 70 eV): m/z (%) = 499 (3), 463 (56), 428 (67), 396 (61), 129 (38), 105 (98), 77 (100). Anal. Calcd for C30H22Cl2N2O5S (593.48): C, 60.71; H, 3.74; N, 4.72. Found: C, 60.80; H, 3.68; N, 4.65.
  • 17 Crystallographic data for compound 3a have been deposited with the accession number CCDC 1041246, and can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk; Web site: www.ccdc.cam.ac.uk/conts/retrieving.html.