Metal-Organic Framework MIL-100 Catalyzed Acetalization of Benzaldehyde with Methanol: Lewis or Bronsted Acid Catalysis?

Metal-organic frameworks (MOFs) are an emerging class of catalyst materials that present the opportunity to develop Lewis acid catalysts with uniform, well-defined, tunable, isolated active sites for a range of chemical transformations. A common example of such a transformation is the acetalization of carbonylic compounds with alcohols over MIL-100. Despite numerous reports focused on the acetalization performance of MIL-100 and related MOF materials, the identity of MIL-100 active sites still remains a point of contention. We present herein a range of catalytic, in situ titration and spectroscopy data that can all plausibly be interpreted under the assumption of the near-exclusive contribution of Bronsted acid sites toward effecting acetalization turnovers over MIL-100(Cr) and MIL-100(Fe). Thermal treatment protocols that simultaneously increase Lewis acid site density and decrease Bronsted acid site density can be used to eliminate more than 90% of MIL-100 mediated turnovers, and infrared spectroscopic signatures indicating the coordination of pyridine to acid sites upon sequential introduction of 2,6-di-tert-butylpyridine (DTBP) followed by pyridine, but not vice versa, are consistent with an attribution of the genesis of Bronsted acid sites to water ligation to open-metal sites. Correlations between MIL-100 degree of hydration, Bronsted acid site density, and net turnover numbers suggest that the involvement of Lewis acid sites, if any, remain minor under the experimental conditions used in this study. Lastly, a decreasing fraction of sites left unititrated by DTBP with lightening diffusion restrictions around the oxo centered trimer indicate that untitrated sites reflect limited access of sterically hindered DTBP, rather than contributions from Lewis acid sites. The principles and methodology used in this study are broadly applicable within the domain of MOF-mediated catalysis, and reinforce the need for a careful evaluation of active site speciation under reaction conditions to more fully realize the promise of MOF materials as Lewis acid catalysts.