Computational Insights into the Regioselectivity of 1,3-Dipolar Cycloadditions inside Carbon Nanotubes

Nature’s enzymes exhibit remarkable substrate specificity and catalytic efficiency by transforming substrates within confined active sites. To emulate this, various molecular containers, including zeolites, cyclodextrins, calix[n]arenes, cavitands, cucurbit[n]urils, metal–organic frameworks, covalent organic frameworks, and carbon nanotubes (CNTs), have been explored. Among these, CNTs are notable for their unique physical and chemical properties, enabling them to control reactions through spatial confinement. This study investigates the effect of CNT encapsulation on metal-free 1,3-dipolar Huisgen cycloaddition reactions between benzyl azide and substituted alkynes. Experimental results showed that CNTs significantly enhance the selectivity for the 1,4-triazole product. Computational studies using density functional theory further elucidate the impact of CNT confinement on reaction mechanisms and regioselectivity. The findings reveal that confinement within CNTs alters potential energy surfaces, favoring 1,4-triazole formation over 1,5-triazole, driven by steric and electronic factors. Additionally, comparative analyses highlight the influence of CNT diameter on activation energies and product stability, particularly with energy decomposition analysis and noncovalent interaction plots. This research underscores the potential of CNTs as nanoscale reactors for controlled synthesis, providing insights into the design of new catalytic systems and advancing the field of molecular encapsulation for selective organic transformations.