Three-Component Synthesis of Imidazopyridine Heterocyclic Compounds in Aqueous Microdroplets

Area of Science:

• Organic Chemistry
• Green Chemistry
• Catalysis

Background:

• The Groebke-Blackburn-Bienaymé (GBB) reaction is a key method for synthesizing biologically active imidazopyridines.
• Previous work showed superacids in microdroplets efficiently catalyze the GBB reaction under ambient conditions.
• Conventional methods often require harsh conditions, high temperatures, or long reaction times.

Purpose of the Study:

• To overcome interfacial saturation limitations in microdroplet GBB reactions.
• To achieve quantitative conversion at the molar scale.
• To develop a greener and more efficient synthesis of imidazopyridine derivatives.

Main Methods:

• Utilized aqueous microdroplets to generate in situ superacids for catalysis.
• Introduced sodium dodecyl sulfate as a co-catalyst to work synergistically with in situ superacids.
• Performed room-temperature synthesis of 19 imidazopyridine derivatives.

Main Results:

• Achieved quantitative conversion at the molar scale by overcoming interfacial saturation.
• Enabled room-temperature synthesis of 19 imidazopyridine derivatives with good yields (62-90%).
• Demonstrated a scalable production rate of 5.25 g/h.

Conclusions:

• The microdroplet-assisted GBB reaction with a co-catalyst offers a green, efficient, and practical alternative.
• This approach aligns with sustainable chemistry principles for synthesizing nitrogen heterocycles.
• Successfully scaled up the synthesis of diverse imidazopyridine derivatives.