Detailed diffuse-reflectance infrared Fourier transform structural analysis of a series of organically modified silicates (ORMOSIL)-entrapped catalysts, varying the molar percentage and the alkyl chain length of the organic group, shows that the important factors affording optimal catalytic performance are two: predominance of six-member siloxane rings (above 80% alkylation) and a low hydrophilicity−lipophilicity balance (HLB). These results provide investigators engaged in developing novel catalysts based on the sol−gel routean advanced chemical technology for synthetic organic/inorganic chemistrywith general guidelines to prepare optimal catalytic materials for a number of relevant applications.