Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett 2016; 27(03): 375-378
DOI: 10.1055/s-0035-1560904
DOI: 10.1055/s-0035-1560904
letter
A Versatile One-Pot Strategy for the Synthesis of [1,4]Thiazepino[5,4-a]isoquinolines Containing Intramolecular Hydrogen Bonds
Further Information
Publication History
Received: 27 August 2015
Accepted after revision: 06 October 2015
Publication Date:
19 November 2015 (online)
![](https://www.thieme-connect.de/media/synlett/201603/lookinside/thumbnails/st-2015-d0675-l_10-1055_s-0035-1560904-1.jpg)
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.
-
References and Notes
- 1a Morton GC, Salvino JM, Labaudinière RF, Herpin TF. Tetrahedron Lett. 2000; 41: 3029
- 1b Venkatesan AM, Gu Y, Dos Santos O, Abe T, Agarwal A, Yang Y, Petersen PJ, Weiss WJ, Mansour TS, Nukaga M, Hujer AM, Bonomo RA, Knox JR. J. Med. Chem. 2004; 47: 6556
- 2a Díaz-Gavilán M, Rodríguez-Serrano F, Gómez-Vidal JA, Marchal JA, Aránega A, Gallo MÁ, Espinosa A, Campos JM. Tetrahedron 2004; 60: 11547
- 2b Garofalo A, Campiani G, Fiorini I, Nacci V. Farmaco 1993; 48: 275
- 3 Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL. Neuropsychopharmacology 2008; 33: 2303
- 4 Sulman FG, Pfeifer Y, Superstine E. Arzneim.-Forsch. 1981; 31: 109
- 5 Kaur H, Kumar S, Chaudhary A, Kumar A. Arabian J. Chem. 2012; 5: 271
- 6 Wehrens XH, Lehnart SE, Reiken SR, Deng S.-X, Vest JA, Cervantes D, Coromilas J, Landry DW, Marks AR. Science 2004; 304: 292
- 7 Ruiz A, Alberdi E, Matute C. Cell Death Dis. 2014; 5: e1156
- 8 Wang L. Comput. Biol. Med. 2009; 39: 355
- 9 Glaser R, Sklarz B. J. Chem. Soc., Perkin Trans. 2 1989; 1031
- 10a Crich D, Rahaman MY. Tetrahedron 2010; 66: 6383
- 10b Braun RU, Müller TJ. J. Tetrahedron 2004; 60: 9463
- 10c Cocco MT, Congiu C, Onnis V. J. Heterocycl. Chem. 1995; 32: 1679
- 11 Goren L, Pappo D, Goldberg I, Kashman Y. Tetrahedron Lett. 2009; 50: 1048
- 12a Allgäuer DS, Mayer P, Mayr H. J. Am. Chem. Soc. 2013; 135: 15216
- 12b Barman PD, Sanyal I, Mandal SB, Banerjee AK. Tetrahedron Lett. 2014; 55: 5648
- 12c Allgäuer DS, Mayr H. Eur. J. Org. Chem. 2013; 6379
- 12d Fernández N, Carrillo L, Vicario JL, Badía D, Reyesa E. Chem. Commun. 2011; 47: 12313
- 13 Hopkin MD, Baxendale IR, Ley SV. Synthesis 2008; 1688
- 14 Maity A, Chakraborty D, Hazra A, Bharitkar YP, Kundu S, Maulik PR, Mondal NB. Tetrahedron Lett. 2014; 55: 3059
- 15a Alizadeh A, Feizabadi M, Bayat F, Zue L.-G. Synlett 2014; 25: 1267
- 15b Alizadeh A, Sadeghi V, Bayat F, Zhu L.-G. Synlett 2014; 25: 2609
- 15c Alizadeh A, Sadeghi V, Bayat F, Zhu L.-G. Helv. Chim. Acta 2014; 97: 1383
- 15d Alizadeh A, Moafi L, Ghanbaripour R, Hossein Abadi M, Zhu Z, Kubicki M. Tetrahedron 2015; 71: 3495
- 15e Rezvanian A, Alizadeh A, Zhu L.-G. Synlett 2012; 23: 2526
- 15f Alizadeh A, Bayat F, Zhu L.-G. Aust. J. Chem. 2014; 67: 949
- 15g Alizadeh A, Zohreh N. Helv. Chim. Acta 2008; 91: 844
- 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.