Oxidized thiourea derivatives: uncovering new frontiers with resonant acoustic mixing (RAM)

Abstract

Nitrogen-containing compounds are essential for producing active pharmaceutical ingredients. However, traditional synthesis methods for these compounds often involve environmentally harmful practices, such as high temperatures, long reaction times, and using toxic reagents and large amounts of solvents. Recently, solvent-free techniques have gained attention as effective and more sustainable alternatives. A significant advancement in this field is resonance acoustic mixing (RAM), a technology that enhances the reactivity of the reaction components without the need for grinding media. RAM operates through vertical oscillations at a constant frequency of 60 Hz, with the G factor adjustable up to 100G. This study investigates the reactivity of thiourea trioxide (TTO), an oxidized thiourea derivative, for preparing 2-amino benzoxazoles. This process efficiently yields the desired aza-heterocycles, with the products easily recovered by simple filtration of the crude reaction mixture. This research highlights the potential of RAM and mechanochemistry to create a more sustainable and efficient synthetic pathway for nitrogen-containing pharmaceutical compounds, promoting greener chemistry practices. Additionally, we evaluated the reactivity of another oxidized derivative of thiourea, thiourea dioxide (TDO), allowing for a comparison between these two compounds.