A facile synthesis of 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines from N-propargylic beta-enaminones

Ibis, Ozge
Zora, Metin
A new and efficient method for the synthesis of 6-chloro-substituted 2-methylene-2,3-dihydro-1,4-oxazepines has been demonstrated. Upon treatment with N-chlorosuccinimide in acetonitrile, N-propargylic beta-enaminones underwent chlorination to afford alpha-chlorinated N-propargylic beta-enaminones, which was then subjected to electrophilic cyclization with zinc chloride in refluxing chloroform to yield 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines. It was shown for the first time that on N-propargylic beta-enaminone systems, alpha-chlorination exclusively preponderates over the formation of chloronium ion. The method was found to be general for a diversity of N-propargylic beta-enaminones and tolerated the presence of a wide range of aryl, heteroaryl and alkyl groups with electron-donating and electron-withdrawing substituents. The method was also applicable as the one-pot two-step process without isolating the intermediate alpha-chlorinated N-propargylic beta-enaminones. This operationally easy method may provide a rapid entry to a library of highly functionalized 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines with potential medicinal applications for human health. (C) 2020 Elsevier Ltd. All rights reserved.


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Synthesis of 3-[(4-Nitrophenyl)thio]-Substituted 4-Methylene-1-pyrrolines from N-Propargylic beta-Enaminones
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A facile and efficient method for the synthesis of 3-[(4-nitrophenyl)thio]-substituted 4-methylene-1-pyrrolines is described. When treated with 4-nitrobenzenesulfenyl chloride in refluxing acetonitrile, N-propargylic beta-enaminones produced alpha-sulfenylated N-propargylic beta-enaminones, which, in the presence of sodium hydride or cesium carbonate, underwent nucleophilic cyclization to afford 4-methylene-3-[(4-nitrophenyl)thio]-1-pyrrolines in good to high yields. It was shown for the first time that on ...
Citation Formats
O. Ibis and M. Zora, “A facile synthesis of 6-chloro-2-methylene-2,3-dihydro-1,4-oxazepines from N-propargylic beta-enaminones,” TETRAHEDRON, pp. 0–0, 2020, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/69593.