Yamasaki Ryu, Ono Mariko, Morita Kento, Ito Ai, Fukuda Kazuo, Okamoto Iwao
Showa Pharmaceutical University, 3-3165 Higashi-tamagawagakuen, Machida, Tokyo 1948543, Japan.
J Org Chem. 2023 Oct 20;88(20):14487-14493. doi: 10.1021/acs.joc.3c01487. Epub 2023 Sep 28.
Methyl substitution at the double bond of -alkenyl anilides influences both the preferred conformation and the susceptibility to acidic hydrolysis. The R-substituted amide favors the trans conformation, whereas amides substituted at R or R favor the cis conformation. Substitution at the R and R positions increases the ratio of the trans conformer. DFT study indicated that these conformational preferences can be explained in terms of substituent-induced torsion twisting of the -alkenyl moiety relative to the amide plane. R substitution enhances the susceptibility to acidic hydrolysis, whereas R or R substitution increases the stability. The effect of the double bond on the conformational effect was showcased by contrasting the preferred conformation of R-substituted anilide (trans) and hydrogenated -isopropyl amide (cis).
α-烯基苯胺双键处的甲基取代会影响其优势构象以及对酸水解的敏感性。R位取代的酰胺有利于反式构象，而R'或R''位取代的酰胺则有利于顺式构象。在R'和R''位进行取代会增加反式构象体的比例。密度泛函理论研究表明，这些构象偏好可以用取代基诱导的α-烯基部分相对于酰胺平面的扭转来解释。R位取代增强了对酸水解的敏感性，而R'或R''位取代则增加了稳定性。通过对比R位取代苯胺（反式）和氢化α-异丙基酰胺（顺式）的优势构象，展示了双键对构象效应的影响。
