Development of a Mechanism-Based Kinetic Model and Process Optimization Incorporating Imidazole Autocatalysis in a 1,1′-Thiocarbonyldiimidazole-Mediated Thiocarbonyl Transfer

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED Organic Process Research & Development Pub Date : 2024-04-30 DOI:10.1021/acs.oprd.4c00099

Bradley J. Paul-Gorsline*,

引用次数: 0

Abstract

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.

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在 1,1′-Thiocarbonyldiimidazole 介导的硫代羰基转移中开发基于机理的动力学模型并进行包含咪唑自催化的工艺优化

混合硫脲 4 的合成是通过 1,1′-硫杂羰基二咪唑 (TCDI) 介导的偶联与 1 形成中间体异硫氰酸酯 2，然后再与胺 3 反应。本研究描述了一个基于机理的动力学模型，旨在了解 2 和杂质 5 的形成过程。该模型的关键在于加入了咪唑自催化作用。通过这个经过实验验证的模型，可以确定改进的工艺条件，从而降低 5 的形成水平。本报告还介绍了咪唑在 4 分解过程中的新发现作用，以及咪唑对 4 和 5 溶解度的影响。

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来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.