Christian H. Hornung

Highly efficient dehydration of carbohydrates to 5-(chloromethyl)furfural (CMF), 5-(hydroxymethyl)furfural (HMF) and levulinic acid by biphasic continuous flow processing

Using a continuous flow reactor, the dehydration of D-fructose and other carbohydrates to 5-(chloromethyl)furfural (1) is achieved in reaction times as short as 60 s. The biphasic flow process allows for high-yielding multigram scale production of CMF (1) which is obtained with excellent purity after a simple extractive work-up. Efficient conversion of D-fructose into 5-(hydroxymethyl)furfural (2) and levulinic acid (6) is also demonstrated using flow reactor techniques.

Synthesis of RAFT Block Copolymers in a Multi-Stage Continuous Flow Process Inside a Tubular Reactor

This work describes a multi-stage continuous flow polymerisation process for the synthesis of block copolymers using the RAFT polymerization method. The process retains all the benefits and versatility of the RAFT method and has been adapted for a series of monomer combinations, including acrylates, acrylamides, and vinyl monomers. It resulted in polymers with molecular weights between 13500 and 34100 g mol–1, and dispersities typically between 1.21 and 1.58. Different architectures were prepared (including combinations of hydrophilic and hydrophobic blocks) which are soluble in a range of different solvents including aqueous and organic media.

Flow Microwave Technology and Microreactors in Synthesis

A bespoke microwave reactor with a glass containment cell has been developed for performing continuous flow reactions under microwave heating. The prototype unit has been evaluated using a series of standard organic chemical transformations enabling scale-up of these chemical processes. As part of the development, a carbon-doped PTFE reactor insert was utilized to allow the heating of poorly absorbing reaction media, increasing the range of solvents and scope of reactions that can be performed in the device.

The fluid flow and heat transfer performance of thermoplastic microcapillary films

This paper is concerned with the evaluation of microcapillary films (MCFs) for microfluidic applications. MCFs are a novel type of low cost plastic film containing continuous arrays of microcapillaries that are extruded from thermoplastics where the capillaries within these films can be round or elliptical with diameters between 30 and 500 µm. The hydrodynamic response of MCFs has been investigated in a series of experiments where the flow within each capillary was laminar with Reynolds numbers up to a maximum of 1800. Pressure drop measurements were consistent with standard laminar flow predictions. A set of experiments involving single- and two-flow systems were conducted to characterize the heat transfer performance of MCFs and the efficacy of heat transfer was found to rank close to that of metallic microfluidic devices. The experimental heat transfer measurements were compared to finite-element model predictions for the MCF geometry and the modelling results were in good agreement with experiment. The overall results demonstrate the viable performance of MCFs for low cost application to examples such as flow within capillaries where temperature profiling is required along the length of the capillaries.

Synthesis of Riboflavines, Quinoxalinones and Benzodiazepines through Chemoselective Flow Based Hydrogenations

Robust chemical routes towards valuable bioactive entities such as riboflavines, quinoxalinones and benzodiazepines are described. These make use of modern flow hydrogenation protocols enabling the chemoselective reduction of nitro group containing building blocks in order to rapidly generate the desired amine intermediates in situ. In order to exploit the benefits of continuous processing the individual steps were transformed into a telescoped flow process delivering selected benzodiazepine products on scales of 50 mmol and 120 mmol respectively.

Continuous flow hydrogenations using novel catalytic static mixers inside a tubular reactor

This work describes a novel continuous flow reactor concept for organic synthesis using heterogeneous catalysts. The concept is based on static mixers coated with a catalytic metal layer, which can be inserted into standard stainless steel reactor tubing. The static mixers were prepared by 3D metal printing, allowing for maximum design flexibility and thus can be tailored to a large number of chemical synthesis applications. The nickel or platinum catalysts were deposited either by metal cold spraying or electrodeposition, which allows for potential scale up and mass production and these techniques are compatible with a range of different catalytic metals. The catalytic flow reactor was evaluated for a series of continuous flow hydrogenations of alkenes and carbonyls.

Looped flow RAFT polymerization for multiblock copolymer synthesis

A looped flow process was designed for the synthesis of well-defined multiblock copolymers using reversible addition–fragmentation chain transfer (RAFT) polymerization. The reaction conditions were optimized to reach high conversions whilst maintaining a high end-group fidelity. The loop set-up proved to be a flexible, robust and time-efficient process for scaling-up multiblock copolymers.

Diels–Alder reactions of myrcene using intensified continuous-flow reactors

This work describes the Diels–Alder reaction of the naturally occurring substituted butadiene, myrcene, with a range of different naturally occurring and synthetic dienophiles. The synthesis of the Diels–Alder adduct from myrcene and acrylic acid, containing surfactant properties, was scaled-up in a plate-type continuous-flow reactor with a volume of 105 mL to a throughput of 2.79 kg of the final product per day. This continuous-flow approach provides a facile alternative scale-up route to conventional batch processing, and it helps to intensify the synthesis protocol by applying higher reaction temperatures and shorter reaction times.

The art of manufacturing molecules

Additively manufactured monolithic reactors allow on-demand synthesis of drug molecules The way we manufacture many of the products used in everyday life, such as the ingredients in shampoo, the plastic components of smartphones, the vitamins and pharmaceuticals we take, and the packaging that all of them come in, has not changed in a significant way over the last hundred years. Arguably, these methods of manufacturing are even older and were already applied in the first large-scale chemical processes in the 19th century, in which new products such as vulcanized rubber, synthetic dyes, or industrial fertilizers were first produced on scales unknown to society at the time. The development of these industrial processes was driven by the benefits of economy of scale, with the aim of centralizing, optimizing, maximizing, and integrating production. In recent years, efforts were made by a series of research groups to reverse this trend and decentralize, miniaturize, and even digitize chemical manufacturing. On page 314 of this issue, Kitson et al. (1) report the synthesis of active pharmaceutical ingredients (APIs) on demand in a three-dimensional (3D)-printed, miniaturized reactor cascade. A complete multistep synthesis of the muscle relaxant baclofen was developed and digitized for remote bench-scale manufacture.

Amination of Aryl Halides and Esters Using Intensified Continuous Flow Processing.

Significant process intensification of the amination reactions of aryl halides and esters has been demonstrated using continuous flow processing. Using this technology traditionally difficult amination reactions have been performed safely at elevated temperatures. These reactions were successfully conducted on laboratory scale coil reactor modules with 1 mm internal diameter (ID) and on a preparatory scale tubular reactor with 6 mm ID containing static mixers.