How Does Silica Catalyze the Amide Bond Formation under Dry Conditions? Role of Specific Surface Silanol Pairs

© 2018 American Chemical Society. The mechanism of the amide bond formation between nonactivated carboxylic acids and amines catalyzed by the surface of amorphous silica under dry conditions is elucidated by combining spectroscopic measurements and quantum chemical simulations. The results suggest a plausible explanation of the catalytic role of silica in the reaction. Both experiment and theory identify very weakly interacting SiOH surface group pairs (ca. 5 Å apart) as key specific sites for simultaneously hosting, in the proper orientation, ionic and canonical pairs of the reactants. An atomistic interpretation of the experiments indicates that this coexistence is crucial for the occurrence of the reaction, since the components of the canonical pair are those undergoing the amidation reaction while the ionic pair directly participates in the final dehydration step. Transition state theory based on quantum mechanical free energy potential energy shows the silica-catalyzed amide formation as being relatively fast. The work also points out that the presence of the specific SiOH group pairs is not exclusive of the adopted silica sample, as they can also be present in natural forms of silica, for instance as hydroxylation defects on α-quartz, so that they could exhibit similar catalytic activity toward the amide bond formation.