Safe and on-demand protocol for the continuous generation of SO2 and Cl2 for subsequent utilization in organic synthesis

Abstract

Hazardous reagents such as sulfur dioxide (SO₂) and chlorine (Cl₂) are powerful and atom-efficient reagents for respectively introducing the ‘SO₂’ moiety and ‘Cl’ atom into organic molecules. However, their use is limited due to a lack of protocols and methods to access them in laboratories readily. This article describes the development of a prototype, method, and process for accessing hazardous gaseous reagents safely on demand continuously for further utilization in organic synthesis. The prototype was validated by producing SO₂ from readily accessible laboratory reagents sodium sulfite (Na₂SO₃) and sulfuric acid (H₂SO₄). The generated SO₂ was successfully utilized for the synthesis of aryl sulfinate salts, which were subsequently converted to sulfonamides and sulfone-containing bicalutamide drugs. The broader applicability of the reactor prototype has also been demonstrated in the generation of chlorine gas from bleach (NaOCl) and hydrochloric acid (HCl), followed by the separation of chlorine gas from an acidic aqueous reaction mixture. The utilization of the separated chlorine gas was demonstrated in the synthesis of silyl chlorides in both batch and continuous manners. The present reactor prototype not only enables safe and convenient access to highly hazardous gaseous reagents for facile organic synthesis in laboratories, but also eliminates the risks in handling, storage, and transportation of hazardous gaseous reagents in cylinders.

Graphical abstract