0009-3122/13/4902-0331©2013 Springer Science+Business Media New York 331 Chemistry of Heterocyclic Compounds, Vol. 49, No. 2, May, 2013 (Russian Original Vol. 49, No. 2, February, 2013) TRANSFORMATIONS OF TETRAHYDRO-1,4-BENZOXAZEPINES AND TETRAHYDRO-1,4-BENZOTHIAZEPINES UNDER THE ACTION OF ALKYNES. FIRST EXAMPLE OF THE SYNTHESIS OF TETRAHYDRO- 1,4-BENZOTHIAZONINE-6-CARBOXYLATE L. G. Voskressensky 1 *, S. V. Akbulatov 1 , T. N. Borisova 1 , L. N. Kulikova 1 , A. V. Listratova 1 , E. A. Sorokina 1 , and A. V. Varlamov 1 It was shown that 2,3,4,5-tetrahydro-1,4-benzoxazepines were cleaved at the N–C(5) bond under the action of activated alkynes in methanol, forming o-(methoxyethyl)- and o-(methoxybenzyl)- phenyl(aminoethyl) ethers. The cleavage rate depended on the electronic effects of the substituents at the C-5 atom. Thiazepine ring expansion in tetrahydro-1,4-benzothiazepine was achieved for the first time via reaction with methyl propiolate to give a benzothiazonine. Keywords: alkynes, benzoxazepine, benzothiazepine, benzothiazonine, domino reaction, ring expansion, ring cleavage. Nine-membered monocyclic and condensed azaheterocycles (azonines) are present in many natural and synthetic molecules, which show high and diverse biological activity [1]. The basic methods for constructing azonines are the expansion of smaller rings [2-4], but there are also methods for synthesis from acyclic precursors [5-7]. Azonines containing a second heteroatom (sulfur, nitrogen, or oxygen) in the nine-membered ring have been much less studied. This type of heterocycle is obtained by sodium periodate oxidation of tetrahydrocarbolines, pyranoindoles [8, 9], benzoxazepines and benzothiazepines condensed with a -lactam ring [10]. Annelated oxazonines can be prepared in modest yield by expansion of the hydrogenated aza rings of annelated N-hydroxypropyl- or N-hydroxyethylpyrrolines and pyridines using cyanogen bromide [11, 12]. We have recently shown the possibility of expanding the tetrahydroazepine ring in isomeric indoloazepines by the use of activated alkynes, that allowed the preparation of tetrahydroazonino[5,6-b]indoles in high yields [13, 14]. We have previously described reactions of tetrahydrobenzodiazepines with alkynes [15]. In the present work, we report the synthesis and reactions of 2,3,4,5-tetrahydro-1,4-benzoxazepines and -1,4-benzothiazepines with alkynes containing electron-withdrawing substituents. The starting 3,5-dimethylphenol (1) or 3-methoxythiophenol (2) were alkylated with bromoacetonitrile to the cyanomethyl ethers 3 and 4. Reduction of the nitrile group in ethers 3 and 4 by lithium aluminum hydride gave the amines 5, 6, which were converted to the N-acyl derivatives 7-10 using acyl chlorides. Cyclization of _______ *To whom correspondence should be addressed, e-mail: lvoskressensky@sci.pfu.edu.ru. 1 Peoples' Friendship University of Russia, 6 Miklukho-Maklaya St., Moscow 117198, Russia. ________________________________________________________________________________________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 357-366, February, 2013. Original article submitted May 23, 2012.