In both frameworks, a small amount of 4-nitrobenzaldehyde is detected in the pores by 1 H NMR digestion studies even after rigorous washing with acetone. After one 8 h run, we detect 0.2-0.3 equiv of 4-nitrobenzaldehyde relative to the benzylamine loading (Figs. and). After five cycles, this value increased slightly to 0.4-0.6 equiv (Figs. and). We hypothesize that the aldehyde substrate may be reacting with our amines to form an off-cycle imine intermediate, which not only restricts access to the pores but also prevents the formation of the desired enamine. Substrate inhibition due to imine formation and pore clogging has been previously observed in primary amine-functionalized mesoporous silica, and is especially pronounced when the pore diameters are less than 3 nm. The formation of off-cycle imines may explain why the initial fourfold difference in activity between 1-templated and 1-nontemplated appears to decrease over longer reaction times. Future work will explore the use of secondary amine sites, which are not able to form stable imines.