(410b) Tuning Acid-Base Cooperative Interactions Between Amines and Silanols Through Controlling the Linker Length

Enzymatic sites often contain acid and base functional groups that act cooperatively to achieve high catalytic rates of conversion.  These sites are precisely organized due to a complex architecture so that the acid and base are colocalized and can separately activate the electrophile and nucleophile, respectively.  The nature of the architecture also imparts a degree of flexibility so that the catalyst and substrates can adopt a favorable conformation to promote the cooperative interaction.  Translating these desirable features of spatial organization of enzyme active sites into simpler catalytic systems has long been a goal in heterogeneous catalysis.

A powerful C-C coupling reaction that has been demonstrated as acid-base cooperative is the aldol condensation, particularly with amines and weakly acidic surface silanols of mesoporous silica.  In the amine-silanol acid-base system, the length and flexibility of the grafted amine can be used to probe the nature of the cooperative interaction of the amine sites with the surface silanols.  Using an array of organosilanes with a stepwise, incremental change in carbon chain length from methyl to pentyl, we report the length dependence of the amine-based organosilane on the rate of reaction and hence the amine-silanol cooperative interactions in the aldol condensation of 4-nitrobenzaldehyde and acetone. 

We find that a propyl linker or longer provides the optimal spatial organization of the amine relative to adjacent silanols in the aldol condensation.  With the least flexibility, the methyl linker inhibits the cooperative interaction, and the reaction proceeds through an alternate non-cooperative mechanism involving imine formation between the surface bound amine and aldehyde.  The intermediate flexibility of the ethyl linker results in an intermediate performance of the catalyst, between that of the propyl and methyl material.  The dramatic differences in catalyst activity demonstrate the overall significance of spatial organization on cooperative catalytic activity.  Additionally, these results have broad implications for other cooperatively catalyzed reactions, including the Knoevenagel condensation and Henry reaction.  Investigations of these reactions have provided more fundamental information about the nature of the acid-base cooperativity of amines and silanols.