Chemoselective cyclodesulfurization vs. dehydration enabled by aqueous microdroplet chemistry

Area of Science:

• Organic Chemistry
• Physical Chemistry
• Chemical Engineering

Background:

• Microdroplet reactions often favor dehydration due to dry air-water interfaces.
• Cyclodesulfurization is a less common reaction pathway in microdroplets.
• 1,3,4-oxadiazoles are important structural motifs in pharmaceuticals.

Purpose of the Study:

• To demonstrate cyclodesulfurization outcompeting dehydration in microdroplets.
• To develop a catalyst-free method for synthesizing 1,3,4-oxadiazoles.
• To investigate the role of the air-water interface in chemoselective transformations.

Main Methods:

• Catalyst-free reaction of benzhydrazide with phenyl isothiocyanate in microdroplets.
• Utilizing online mass spectrometry to detect transient reactive intermediates.
• Investigating reaction kinetics influenced by reagent concentration and droplet travel distance.

Main Results:

• A two-step cyclodesulfurization reaction was achieved under ambient conditions.
• Transient reactive oxygen species at the interface oxidized thiol intermediates.
• Hydroxyl-mediated nucleophilic attack led to the formation of 1,3,4-oxadiazole.
• Dehydration was notably absent, contrary to typical microdroplet reactions.

Conclusions:

• Microdroplet environments can promote chemoselective cyclodesulfurization over dehydration.
• Interfacial reactive oxygen species play a critical role in directing the reaction pathway.
• Charged microdroplets offer unique potential for novel chemical transformations.