Mechanochemistry Frees Thiourea Dioxide (TDO) from the ‘Veils’ of Solvent, Exposing All Its Reactivity

Abstract

The synthesis of nitrogen-based heterocycles has always been considered essential in developing pharmaceuticals in medicine and agriculture. This explains why various synthetic approaches have been proposed in recent decades. However performing as methods, they often imply harsh conditions or the employment of toxic solvents and dangerous reagents. Mechanochemistry is undoubtedly one of the most promising technologies currently used for reducing any possible environmental impact, addressing the worldwide interest in counteracting environmental pollution. Following this line, we propose a new mechanochemical protocol for synthesizing various heterocyclic classes by exploiting thiourea dioxide (TDO)’s reducing proprieties and electrophilic nature. Simultaneously exploiting the low cost of a component of the textile industry such as TDO and all the advantages brought by a green technique such as mechanochemistry, we plot a route towards a more sustainable and eco-friendly methodology for preparing heterocyclic moieties.

Mechanosynthesis of sulfonamides via a telescopic, environmentally friendly, and cost-effective process

“…[42][43][44][45][46][47][48][49][50][51][52][53][54] In this study, we discovered a promising combination between 4-nitro sulfonyl chloride 2d and amines 9 and 10 (Scheme 4), which gave access to highly suitable moieties for APIs. [55][56][57] Unfortunately, the synthetic route defined above was found to be unfairly suitable for the mechanosynthesis of pharmaceuticals (9d and 10d). Furthermore, the reaction involving amines 9 and 10 did not proceed, perhaps due to the formation of a sticky solid mixture.…”

“…42–54 In this study, we discovered a promising combination between 4-nitro sulfonyl chloride 2d and amines 9 and 10 (Scheme 4), which gave access to highly suitable moieties for APIs. 55–57…”

Mechanically accelerated catalytic hydrogenation: correlating physical state, reaction rate, and interface area

“…Mechanochemistry offers a broad range of synthetic methods that enable access to various active pharmaceutical ingredients (APIs) and chemicals. 9 This success can be attributed to the adequate forced mixing of chemical species induced by severe mechanical deformation on a molecular scale. 10,11 However, when mechanochemical conditions are applied to organic systems, it is essential to note some differences from inorganic materials.…”

Chemistry of Sodium Hydroxymethanesulfinate and Thiourea Oxides: New Data

“…Это может быть причиной неоднократно наблюдавшегося быстрого самопроизвольного экзотермического разложения твердого диоксида тиомочевины [1]. Возможность протекания этого процесса при хранении ДОТМ и его использовании в механохимическом синтезе [37] необходимо учитывать, особенно при высокой влажности.…”