The synthesis of mixed thiourea 4 was performed via a 1,1′-thiocarbonyldiimidazole (TCDI)-mediated coupling with 1 to form intermediate isothiocyanate 2 prior to reaction with amine 3. A critical undesired thiourea impurity─5─is formed via the overreaction of 2 with an additional equivalent of 1. This work describes a mechanism-based kinetic model toward understanding the formation of 2 and impurity 5. Critical to the construction of this model is the inclusion of imidazole autocatalysis. This experimentally validated model allows for the identification of improved process conditions for reducing the level of formation of 5. This report also describes the newfound role of imidazole in the decomposition of 4 and the impact of imidazole on the solubility of both 4 and 5.

中文翻译：

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在 1,1'-硫代羰基二咪唑介导的硫代羰基转移中结合咪唑自催化的基于机理的动力学模型和过程优化的开发

混合硫脲4的合成是通过 1,1'-硫代羰基二咪唑 (TCDI) 介导的与1 的偶联形成中间体异硫氰酸酯2，然后与胺3反应。2与另外当量的1发生过度反应，形成一种重要的不需要的硫脲杂质─ 5。这项工作描述了一个基于机制的动力学模型，旨在理解2和杂质5的形成。构建该模型的关键是包含咪唑自催化。这个经过实验验证的模型可以识别改进的工艺条件，以减少5的形成水平。该报告还描述了咪唑在4分解中新发现的作用以及咪唑对4和5溶解度的影响。