N-Ethynylation of Anilides Decreases the Double-Bond Character of Amide Bond while Retaining trans-Conformation and Planarity |
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Authors: | Dr. Ryu Yamasaki Kento Morita Hiromi Iizumi Dr. Ai Ito Dr. Kazuo Fukuda Prof. Dr. Iwao Okamoto |
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Affiliation: | Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo, 194-8543 Japan |
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Abstract: | Activated amide bonds have been attracting intense attention; however, most of the studied moieties have twisted amide character. To add a new strategy to activate amide bonds while maintaining its planarity, we envisioned the introduction of an alkynyl group on the amide nitrogen to disrupt amide resonance by nN→Csp conjugation. In this context, the conformations and properties of N-ethynyl-substituted aromatic amides were investigated by DFT calculations, crystallography, and NMR spectroscopic analysis. In contrast to the cis conformational preference of N-ethyl- and vinyl-substituted acetanilides, N-ethynyl-substituted acetanilide favors the trans conformation in the crystal and in solution. It also has a decreased double bond character of the C(O)−N bond, without twisting of the amide. N-Ethynyl-substituted acetanilides undergo selective C(O)−N bond or N−C(sp) bond cleavage reactions and have potential applications as activated amides for coupling reactions or easily cleavable tethers. |
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Keywords: | alkynes amides acylation conformational analysis ynamides |
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