Are activation barriers of 50–70 kcal mol−1 accessible for transformations in organic synthesis in solution?

Abstract

High-temperature organic chemistry represents a transformative approach for accessing reaction pathways previously considered unattainable under conventional conditions. This study focuses on a high-temperature synthesis as a powerful method for performing solution-phase organic reactions at temperatures up to 500 °C. Using the isomerization of N-substituted pyrazoles as a model reaction, we demonstrate the ability to overcome activation energy barriers of 50–70 kcal mol⁻¹, achieving product yields up to 50% within reaction times as short as five minutes. The methodology is environmentally friendly, leveraging standard glass capillaries and p-xylene as a solvent. The significance of high-temperature synthesis lies in its simplicity, efficiency, and ability to address the limitations of traditional methods in solution chemistry. Kinetic studies and DFT calculations validate the experimental findings and provide insights into the reaction mechanism. The method holds broad appeal due to its potential to access diverse compounds relevant to pharmaceuticals, agrochemicals, and materials science. By expanding the scope of accessible reactions, this exploration of experimental possibilities opens a new frontier in synthetic chemistry, enabling the exploration of previously inaccessible transformations. This study establishes a new direction for further innovations in organic synthesis, fostering advancements in both fundamental research and practical applications.