The conformational preferences of N‐((6‐methylpyridin‐2‐yl)carbamothioyl)benzamide were studied in solution, the gas phase and the solid state via a combination of NMR, density functional theory (DFT) and single crystal X‐ray techniques. This acyl thiourea derivative can adopt two classes of low energy conformation, each stabilized by a different 6‐membered intramolecular hydrogen bond (IHB) pseudoring. Analysis in different solvents revealed that the conformational preference of this molecule is polarity dependent, with increasingly polar environments yielding a higher proportion of the minor conformer containing an NH…N IHB. The calculated barrier to interconversion is consistent with dynamic behaviour at room temperature, despite the propensity of 6‐membered IHB pseudorings to be static. This work demonstrates that introducing competitive IHB pathways can render static IHBs more dynamic and that such systems could have potential as chameleons in drug design.

中文翻译：

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竞争性分子内氢键：为分子提供选择

通过核磁共振、密度泛函理论 (DFT) 和单晶 X 射线技术的结合，研究了 N-((6-甲基吡啶-2-基)氨基甲酰基)苯甲酰胺在溶液、气相和固态中的构象偏好。这种酰基硫脲衍生物可以采用两类低能构象，每种构象都由不同的六元分子内氢键 (IHB) 假环稳定。在不同溶剂中的分析表明，该分子的构象偏好取决于极性，随着极性环境的增加，会产生更高比例的含有 NH…N IHB 的次要构象异构体。尽管 6 元 IHB 假环倾向于静态，但计算出的互变势垒与室温下的动态行为一致。这项工作表明，引入竞争性 IHB 途径可以使静态 IHB 更具动态性，并且此类系统在药物设计中可能具有变色龙的潜力。