Pressure-accelerated azide-alkyne cycloaddition: micro capillary versus autoclave reactor performance.

Area of Science:

• Organic Chemistry
• Chemical Engineering
• Process Intensification

Background:

• High pressure influences regioselectivity and yield in cycloaddition reactions.
• Limited availability of high-pressure equipment restricts its synthetic applications.
• Microflow reactors offer established advantages under standard conditions.

Purpose of the Study:

• To apply novel-process-window (NPW) principles to azide-alkyne cycloaddition.
• To synthesize a key precursor for Rufinamide using intensified reaction conditions.
• To compare the performance of batch and flow reactors under varying pressures and activation methods.

Main Methods:

• Investigated uncatalyzed and catalyzed azide-alkyne cycloaddition.
• Employed three activation methods: uncatalyzed batch, uncatalyzed flow, and catalyzed flow.
• Compared a high-pressure autoclave batch reactor (up to 1800 bar) with a capillary flow reactor (up to 400 bar).

Main Results:

• Achieved significant reaction speedup and increased space-time yields.
• Widened the operational process window for selective Rufinamide precursor synthesis with good yields.
• Demonstrated the effectiveness of NPW principles in intensifying the cycloaddition reaction.

Conclusions:

• High temperature, pressure, and concentration effectively intensify azide-alkyne cycloaddition kinetics.
• Both batch and flow reactors show potential, with optimized conditions yielding superior results.
• The methodology was successfully applied to other azide-alkyne cycloadditions, broadening its scope.