Development of aerobic oxidation methods is of critical importance for the advancement of green chemistry, where the only byproduct produced is water. Recent work by our lab has produced an efficient Pd based heterogenous catalyst capable of preforming the aerobic oxidation of a wide spectrum of alcohols to either carboxylic acid or methyl ester. The well-defined catalyst PdBi0.35Te0.23/C (PBT/C) catalyst has been shown to can perform the aerobic oxidation of alcohols to carboxylic acids in basic conditions. Additionally, we explored this catalyst for a wide range of alcohols and probed the nature of the selectivity of PBT/C for methyl esterification over other side products. Finally, means by which the catalyst operates with respect to oxidation states of the three components, Pd, Bi, and Te, was probed. Carboxylic acids are an important functional group due to their prevalence in various pharmaceutically active agents, agrochemicals, and commodity scale chemicals. The well-defined catalyst PBT/C catalyst was discovered to be effective for the oxidation of a wide spectrum of alcohols to carboxylic acid. The demonstrated substrate scope and functional group tolerance are the widest reported for an aerobic heterogeneous catalyst. Additionally, the catalyst has been implemented in a packed bed reactor with quantitative yield of benzoic acid maintained throughout a two-day run. Biomass derived 5-(hydroxymethyl)furfural (HMF) is also oxidized to 2,5-furandicarboxylic acid (FDCA) in high yield. Exploration of PBT/C for the oxidative methyl esterification was found to exhibit exquisite selectivity for the initial oxidation of primary alcohol instead of methanol, which is the bulk solvent. We explored this selectivity and conclude that it results from various substrate-surface interactions, which are not attainable by methanol. The primary alcohol can outcompete the methanol for binding on the catalyst surface through various interactions between the side chain of the alcohol solvent and the surface of the catalyst: (listed in order of strength) lone pair-surface (heterocyclic primary alcohols)> [pi]-surface (aryl primary alcohols)> van der Waals-surface (alkyl primary alcohols). These interactions were previously underappreciated in condensed phase heterogeneously catalyzed aerobic oxidations. 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. We report X-ray absorption spectroscopic studies of the heterogenous catalyst. These 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. The data also suggest formation of a Pd-Te alloy phase that modifies the electronic properties of the Pd catalyst. Collectively, these results provide valuable insights into the synergistic benefits of multiple promoters in heterogeneous catalytic oxidation reactions.

This book deals with the search for environmentally benign procedures for the oxidation of alcohols and gives an overview of their transition-metal-catalyzed aerobic oxidation.

The first book to place recent academic developments within the context of real life industrial applications, this is a timely overview of the field of aerobic oxidation reactions in the liquid phase that also illuminates the key challenges that lie ahead. As such, it covers both homogeneous as well as heterogeneous chemocatalysis and biocatalysis, along with examples taken from various industries: bulk chemicals and monomers, specialty chemicals, flavors and fragrances, vitamins, and pharmaceuticals. One chapter is devoted to reactor concepts and engineering aspects of these methods, while another deals with the relevance of aerobic oxidation catalysis for the conversion of renewable feedstock. With chapters written by a team of academic and industrial researchers, this is a valuable reference for synthetic and catalytic chemists at universities as well as those working in the pharmaceutical and fine chemical industries seeking a better understanding of these reactions and how to design large scale processes based on this technology.

Transformation of hydrocarbon feedstocks to complex molecules found in the fine chemical, agro chemical, and pharmaceutical industries require selective oxidations to impart the desired functionality. Oxidation of alcohols is commonly done employing harsh and potentially hazardous oxidants with stoichiometric amounts of byproducts being produced. The use of O2 as the terminal oxidant provides a safe and environmentally benign alternative with selectivity control being realized through the use of a catalyst. The use of a Ru(OH)x/Al2O3 catalyst for the oxidation of alcohols to aldehydes or ketones was studied for applicability and scalability in a continuous process. The catalyst was found to undergo rapid deactivation in the first 50-100 turnovers. High yields of diverse aldehydes and ketones were realized in the continuous process over the deactivated Ru(OH)x/Al2O3 catalyst. The discovery of a new heterogeneous catalyst was accomplished through rapid admixture screening and optimization using design of experiment techniques. The optimized catalyst compositions of PdBi0.47Te0.09/C (PBT-1) and PdBi0.35Te0.23/C (PBT-2) were found to be very active and selective for the aerobic oxidation of 1-octanol to methyl octanoate. These optimized catalysts show high yields of many diverse methyl esters from the oxidation of alcohols, and their stability was demonstrated in a continuous process achieving nearly 60,000 turnovers with no apparent loss in activity. The role of the Bi and Te promoters and mechanism of the PBT-2 catalyst was explored through kinetic studies and characterization of the catalyst. Through the use of kinetics and other mechanistic probes we discovered that the reaction shows saturation dependence in [substrate] and [K2CO3] and is first order in pO2, supporting a Langmuir-Hinshelwood mechanism with the reaction occurring between alkoxide and O2 adsorbed to the catalyst. The promoters are proposed to protect the Pd catalyst from over oxidation to inactive PdOx species as well as prevent side reactions (Bi) and electronically modify the Pd (Te). Oxidation of alcohols to aldehydes or nitriles was demonstrated in a continuous process using a CuI/TEMPO catalyst. The oxidation to the nitrile was accomplished through the addition of anhydrous ammonia, and excellent yields were observed from the oxidation of diverse primary benzylic alcohols.

The selective oxidation of C-H bonds in (hetero)aromatics provides an efficient access to functionalized aromatic molecules of industrial interest. Aerobic oxygen is an ideal terminal oxidants for this transformation because it is readily available and often produces water as the sole byproduct. Homogeneous palladium catalysts are eminently compatible with aerobic turnovers and have seen success in numerous aerobic oxidation processes (e. g., alkene oxidation, alcohol oxidation). In contrast, palladium-catalyzed aerobic oxidative C-H functionalization has been rather underdeveloped. Challenges include slow catalytic turnover, catalyst decomposition and lack of selectivity control (e.g., site selectivity, homo- vs. cross-coupling selectivity). This thesis presents three research projects with different approaches to tackle the unsolved problems in the reaction class of palladium-catalyzed aerobic C-H oxidation of (hetero)aromatics. The reaction mechanism of C-H/C-H coupling of [o]-xylene was characterized, which disclosed a novel, bimetallic pathway. Built on this work, the effect of copper cocatalyst in this reaction was investigated, which revealed a non-traditional role of copper salt in oxidative palladium catalysis and led to the discovery of an improved catalyst system. Last, a synthetic methodology for aerobic indole C-H arylation with ligand-controlled site selectivity was developed, which provided efficient access to pharmaceutically-relevant aryl indoles and led to preliminary mechanistic insights into regiocontrol.

Oxidation reactions are an important chemical transformation in both academia and industry. Among the major advances in the field has been the development of catalytic processes, which are not only selective and efficient, but also allow the replacement of common stoichiometric oxidants with molecular oxygen, ideally from air at atmospheric pressure. This results in processes with higher atom efficiency, where water is the only side product in line with the principles of green chemistry. Focusing on the use of molecular oxygen as the terminal oxidant, this book covers recent advances in both heterogeneous and homogeneous systems, with and without metals and on the “taming” of the highly reactive oxygen gas by use of micro-flow reactors and membranes. A useful reference for industrial and academic chemists working on oxidation processes, as well as green chemists.