In the present study, we demonstrate the utility of "admixture screening" for the discovery of new multicomponent heterogeneous Pd catalyst compositions that are highly effective for aerobic oxidative methyl esterification of primary alcohols. The identification of possible catalysts for this reaction was initiated by the screening of simple binary and ternary admixtures of Pd/charcoal in combination with one or two metal and/or metalloid components as the catalyst. This approach permitted rapid evaluation of over 400 admixture combinations for the oxidative methyl esterification of 1-octanol at 60 °C in methanol. Product yields from these reactions varied widely, ranging from 2% to 88%. The highest yields were observed with Bi-, Te-, and Pb-based additives, and particularly from those containing both Bi and Te. Validation of the results was achieved by preparing specific PdBiTe catalyst formulations via a wet-impregnation method, followed by application of response surface methodology to identify the optimal Pd-Bi-Te catalyst stoichiometry. This approach revealed two very effective catalyst compositions: PdBiTe/C (PBT-1) and PdBiTe/C (PBT-2). The former catalyst was used in batch aerobic oxidation reactions with different primary alcohols and shown to be compatible with substrates bearing heterocycle and halide substituents. The methyl ester products were obtained in >90% yield in nearly all cases. Implementation of the PBT-2 catalyst in a continuous-flow packed-bed reactor achieved nearly 60 000 turnovers with no apparent loss of catalytic activity.

Heterogeneous catalytic aerobic oxidation methods represent a near-ideal approach for the conversion of primary alcohols to carboxylic acids. Here, we report that a heterogeneous catalyst composed of Pd, Bi, and Te supported on activated carbon is highly effective for the oxidation of diverse benzylic and aliphatic primary alcohols, including 5-(hydroxymethyl)furfural (HMF) and substrates bearing heterocycles and other important functional groups. In many cases, the desired carboxylic acid product is obtained in >90% yield. Additionally, the catalyst has been demonstrated in a continuous-flow packed-bed reactor for the oxidation of benzyl alcohol, achieving near-quantitative yield while undergoing over 30 000 turnovers.

Aerobic oxidative methyl esterification of primary alcohols is an important chemical transformation that converts a nucleophile (alcohol) into a versatile electrophile (methyl ester). We recently discovered a heterogeneous PdBiTe/C catalyst that exhibits the highest activity yet reported for this transformation. Bi and Te serve as synergistic promoters that enhance both the rate and yield of the reactions relative to reactions employing Pd alone or Pd in combination with Bi or with Te as the sole promoter. Here, we report a mechanistic study of the oxidative methyl esterification of benzyl alcohol and 1-octanol to provide insights into the overall multistep transformation as well as the role of the Bi and Te in the reaction. The catalytic rates of the oxidative esterification of benzyl alcohol and octanol with Pd, PdBi, PdTe, and PdBiTe catalysts exhibit a saturation dependence on [alcohol] and [K2CO3] and a first-order dependence on pO2. Hammett studies of benzyl alcohol oxidation reveal opposing electronic trends for initial rates of oxidation of alcohol to aldehyde (negative ρ value) and the oxidation of aldehyde to methyl ester (positive ρ value). These data and complementary kinetic isotope effect data support a Langmuir–Hinshelwood mechanism in which a surface-bound alkoxide or hemiacetal intermediate undergoes rate-limiting β-hydride elimination. Molecular oxygen participates in this process, as revealed by a first-order dependence on pO2. X-ray photoelectron and X-ray absorption spectroscopic methods show that the promoters undergo oxidation in preference to Pd, maintaining the Pd surface in the active metallic state and preventing inhibition by surface Pd-oxide formation. Collectively, these results provide valuable insights into the synergistic benefits of multiple promoters in heterogeneous catalytic oxidation reactions.