A Mild and Efficient Flow Procedure for the Transfer Hydrogenation of Ketones and Aldehydes using Hydrous Zirconia

A flow chemistry Meerwein–Ponndorf–Verley (MPV) reduction procedure using partially hydrated zirconium oxide <i>via</i> a machine-assisted approach is reported. The heterogeneous reductive system could be applied to a wide range of functionalized substrates, allowing clean and fast delivery of the alcohol products within a few minutes (6–75 min). In three examples the system was scaled to deliver 50 mmol of product

Mild and Selective Heterogeneous Catalytic Hydration of Nitriles to Amides by Flowing through Manganese Dioxide

A sustainable flow chemistry process for the hydration of nitriles, whereby an aqueous solution of the nitrile is passed through a column containing commercially available amorphous manganese dioxide, has been developed. The product is obtained simply by concentration of the output stream without any other workup steps. The protocol described is rapid, robust, reliable, and scalable, and it has been applied to a broad range of substrates, showing a high level of chemical tolerance

Sustainable Flow Oppenauer Oxidation of Secondary Benzylic Alcohols with a Heterogeneous Zirconia Catalyst

A flow chemistry process for the Oppenauer oxidation of benzylic secondary alcohols using partially hydrated zirconium oxide and a simple carbonyl containing oxidant such as acetone, cyclohexanone, and neopentanal is reported. The heterogeneous oxidative system could be applied to a wide range of functionalized alcohol substrates, allowing clean and fast delivery of ketone products within a few minutes between 40 and 100 °C

Process Intensification for the Continuous Flow Hydrogenation of Ethyl Nicotinate

Here we report a process intensification study for the selective, partial, and full hydrogenation of ethyl nicotinate using a trickle bed reactor for meso-flow transformations (HEL FlowCAT). The process achieved a throughput of 1219 g d^–1 (78 g h^–1 of product per g of active catalyst) for the partial hydrogenation to ethyl 1,4,5,6-tetrahydropyridine-3-carboxylate, whereas the productivity for the full hydrogenation process reached a 1959 g d^–1 of throughput (408 g h^–1 of product per g of active catalyst) on this laboratory-scale flow chemistry platform

Flow Heck Reactions Using Extremely Low Loadings of Phosphine-Free Palladium Acetate

High-yielding Heck reactions are demonstrated using 0.05 mol % Pd(OAc)₂ without phosphine ligands. These reactions are run in a mesoscale flow reactor which allows precise control of reaction times and temperatures. Profiling yield and selectivity versus Pd loading shows 500 ppm to be optimal for aryl iodides; higher loadings favor side reactions caused by Pd(II) species. Aryl halides are examined via concise Design of Experiment to expand the scope and optimize conditions

Systematic Optimization of Liquid–Liquid Extraction for Isolation of Unidentified Components

We present a systematic approach for predicting the best solvents for selective extraction of components with unknown structure from complex mixtures (e.g., natural products)a tool promising dramatic simplification of extraction process optimization. Its key advantage is that identification of the component(s) is unnecessaryprediction is based on a small set of experimental distribution coefficients (obtained using a combination of shake-flask extraction and chromatographic analysis) rather than structure-based descriptors. The methodology is suitable for the very common situations in practice where the desired compound needs to be separated from unknown impurities (i.e., selectively extracted from the mixture), as well as for large-scale and high-throughput work. The proof-of-concept methodology was developed and evaluated using an extensive set of experimental distribution data of lignin-related compounds obtained in this work

Process Development of CuI/ABNO/NMI-Catalyzed Aerobic Alcohol Oxidation

An improved Cu/nitroxyl catalyst system for aerobic alcohol oxidation has been developed for the oxidation of functionalized primary and secondary alcohols to aldehydes and ketones, suitable for implementation in batch and flow processes. This catalyst, which has been demonstrated in a >50 g scale batch reaction, addresses a number of process limitations associated with a previously reported (^MeObpy)­Cu^I/ABNO/NMI catalyst system (^MeObpy = 4,4′-dimethoxy-2,2′-bipyridine, ABNO = 9-aza­bicyclo­[3.3.1]­nonane <i>N</i>-oxyl, NMI = <i>N</i>-methyl­imid­azole). Important catalyst modifications include the replacement of [Cu­(MeCN)₄]­OTf with a lower-cost Cu source, CuI, reduction of the ABNO loading to 0.05–0.3 mol%, and use of NMI as the only ligand/additive (i.e., without a need for ^MeObpy). Use of a high flash point solvent, <i>N</i>-methyl­pyrrol­idone, enables safe operation in batch reactions with air as the oxidant. For continuous-flow applications compatible with elevated gas pressures, better performance is observed with acetonitrile as the solvent