Yamasaki Ryu, Morita Kento, Iizumi Hiromi, Ito Ai, Fukuda Kazuo, Okamoto Iwao
Showa Pharmaceutical University, 3-3165 Higashi-Tamagawagakuen, Machida, Tokyo, 194-8543, Japan.
Chemistry. 2019 Aug 1;25(43):10118-10122. doi: 10.1002/chem.201901451. Epub 2019 Jun 26.
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→C 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.
活化的酰胺键一直备受关注；然而，大多数研究的部分具有扭曲的酰胺特征。为了在保持酰胺键平面性的同时增加一种活化酰胺键的新策略，我们设想在酰胺氮上引入一个炔基，通过nN→C共轭破坏酰胺共振。在此背景下，通过密度泛函理论（DFT）计算、晶体学和核磁共振光谱分析研究了N-乙炔基取代的芳香酰胺的构象和性质。与N-乙基和乙烯基取代的乙酰苯胺的顺式构象偏好相反，N-乙炔基取代的乙酰苯胺在晶体和溶液中更倾向于反式构象。它还具有降低的C（O）-N键双键特征，而酰胺没有扭曲。N-乙炔基取代的乙酰苯胺会发生选择性的C（O）-N键或N-C（sp）键裂解反应，并具有作为偶联反应的活化酰胺或易于裂解的连接基团的潜在应用。
