A novel method for the synthesis of pyrido[1,2-b][2]benzazepine derivatives is based on the reaction of 2-(bromomethyl)benzophenones and 2-(bromomethyl)benzaldehyde with 2-methylpyridines. The route of synthesis of 6H-pyrido[1,2-b][2]benzazepinium salts includes several steps with the possibility of isolating intermediate 1-benzyl-2-methylpyridinium and 11-aryl-11-hydroxy-11,12-dihydro-6Hpyrido[1,2-b][2]benzazepinium bromides. The efficiency of dehydration of intermediate carbinols increases with the use of protic solvents, an increase in heating time, and in the presence of electron-withdrawing substituents in the benzazepine moiety. The structure of the reaction products was proved by mass spectrometry, IR and one- and two-dimensional correlation NMR spectroscopy.
Similar content being viewed by others
References
(a) Heinrich, M.; Lee, T. H. J. Ethnopharmacol. 2004, 92, 147. (b) Zhang, Y.; Shen, S.; Fang, H.; Xu, T. Org. Lett. 2020, 22, 1244. (c) Li, S.; Li, X.; Zhang, T.; Kamara, M. O.; Liang, J.; Zhu, J.; Meng, F. Bioorg. Chem. 2020, 94, 103385. (d) Wang, L.; Yin, Z. Q.; Cai, Y.; Zhang, X. Q.; Yao, X. S.; Ye, W. C. Biochem. Syst. Ecol. 2010, 38(3), 444. (e) Hasebein, P.; Aulinger, K.; Schepmann, D.; Wünsch, B. Tetrahedron 2013, 69, 4552. (f) Soto-Otero, R.; MéndezÁlvarez, E.; Sánchez-Iglesias, S.; Labandeira-García, J. L.; Rodríguez-Pallares, J.; Zubkov, F. I.; Zaytsev, V. P.; Voskressensky, L. G.; Varlamov, A. V.; de Candia, M.; Fiorella, F.; Altomare, C. Arch. Pharm. (Weinheim, Ger.) 2012, 345, 598.
(a) Zhao, R. Y.; Zhuo, X.; Yang, Q.; Zhao, L.; Huang, Yu.; Ye, H.; Yang, C.; Lei, J.; Gai, S.; Guo, H.; Jia, J.; Bai, L.; Xie, H.; Zhou, X.; Guo, Z.; Li, W.; Cao, M.; Zheng, J.; Ye, Z.; Yang, Y. WO Patent 202006722. b Wang, L.-L.; Han, H.-B.; Cui, Z.-H.; Zhao, J.-W.; Bu, Z.-W.; Wang, Q.-L. Org. Lett. 2020, 22, 873. (c) Meng, F.; Li, S.; Zhu, J.; Xu, H.; Li, X.; Wang, L.; Zhang, T.; Liang, J.; Sun, Q.; Zhao, N. CN Patent 110172058.
Simic, M. R.; Stankovic, M.; Mandic, B. M.; Tesevic, V. V.; Savic, V. M. Arch. Pharm. (Weinheim, Ger.) 2015, 348, 100.
Houlihan W.; Nadelson J. US Patent 3892752; Сhem. Аbstr. 1975, 83, 178856.
(a) Borsini, E.; Broggini, G.; Colombo, F.; Khansaa, M.; Fasana, A.; Galli, S.; Passarella, D.; Riva, E.; Riva, S. Tetrahedron: Asymmetry 2011, 22, 264. (b) Cleghorn, L. A. T.; Grigg, R.; Kilner, C.; MacLachlan, W. S.; Sridharan, V. Chem. Commun. 2005, 24, 3071. (c) Santos, L. S.; Pilli, R. A. Synthesis 2002, 87. (d) Ikeda, M.; Akamatsu, S.; Kugo, Y.; Sato, T. Heterocycles 1996, 42, 155.
(a) Maruyama, K.; Ogawa, T.; Kubo, Y.; Araki, T. J. Chem. Soc., Perkin Trans. 1 1985, 2025. (b) Maruyama, K.; Kubo, Y. Chem. Lett. 1978, 769.
(a) Neumann, R.; Herz, H.-G.; Maas, G. Z. Naturforsch., B: J. Chem. Sci. 2002, 57(4), 427. (b) Reinhard, R.; Glaser, M.; Neumann, R.; Maas, G. J. Org. Chem. 1997, 62, 7744.
Gorulya, A. P.; Tverdokhlebov, A. V.; Tolmachev, A. A.; Shishkin, O. V.; Shishkina, S. V. Tetrahedron 2011, 67, 1030.
(a) Cheng, Y.; Yang, H.-B.; Wang, M.-X.; Williams, D. J. Tetrahedron 2002, 58, 2821. (b) Li, X.; Zhou, G.; Du, X.; Wang, T.; Zhang, Z. Org. Lett. 2019, 21, 5630.
Bradsher, C. K.; Quin, L. D.; Le Bleu, R. E. J. Org. Chem. 1961, 26, 3278.
(a) Kovtunenko, V. A.; Potikha, L. M.; Sypchenko, V. V.; Zubatyuk, R. I.; Shishkin, O. V. J. Chem. Res. 2012, 6, 312. (b) Potikha, L. M.; Sypchenko, V.; Davydov, V. Fr.-Ukr. J. Chem. 2019, 7(1), 96.
Zhang, X. X.; Lippard, S. J. J. Org. Chem. 2000, 65(17), 5298.
Gobbi, S.; Cavalli, A.; Negri, M.; Schewe, K. E.; Belluti, F.; Piazzi, L.; Hartmann, R. W.; Recanatini, M.; Bisi, A. J. Med. Chem. 2007, 50, 3420.
Kim, D. H.; Santilli, A. A.; Sulkowski, T. S.; Childress, S. J. J. Org. Chem. 1967, 32, 3720.
Author information
Authors and Affiliations
Corresponding author
Additional information
Translated from Khimiya Geterotsiklicheskikh Soedinenii, 2020, 56(11), 1454–1459
Supplementary Information
ESM 1
(PDF 21014 kb)
Rights and permissions
About this article
Cite this article
Potikha, L.M., Sypchenko, V.V. & Kovtunenko, V.A. A novel method for the synthesis of pyrido[1,2-b][2]benzazepines on the basis of 2-(bromomethyl)benzophenones and 2-(bromomethyl)benzaldehyde. Chem Heterocycl Comp 56, 1454–1459 (2020). https://doi.org/10.1007/s10593-020-02837-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10593-020-02837-8