Ex-situ generation and synthetic utilization of bare trifluoromethyl anion in flow via rapid biphasic mixing.

Fluoroform (CF3H) is the simplest reagent for nucleophilic trifluoromethylation intermediated by trifluoromethyl anion (CF3-). However, it has been well-known that CF3- should be generated in presence of a stabilizer or reaction partner (in-situ method) due to its short lifetime, which results in the fundamental limitation on its synthetic utilization. We herein report a bare CF3- can be ex-situ generated and directly used for the synthesis of diverse trifluoromethylated compounds in a devised flow dissolver for rapid biphasic mixing of gaseous CF3H and liquid reagents that was designed and structurally optimized by computational fluid dynamics (CFD). In flow, various substrates including multi-functional compounds were chemoselectively reacted with CF3-, extending to the multi-gram-scale synthesis of valuable compounds by 1-hour operation of the integrated flow system.

Modular Flow Reactors for Valorization of Kraft Lignin and Low-Voltage Hydrogen Production.

Recent studies have found that green hydrogen production and biomass utilization technologies can be combined to efficiently produce both hydrogen and value-added chemicals using biomass as an electron and proton source. However, the majority of them have been limited to proof-of-concept demonstrations based on batch systems. Here the authors report the design of modular flow systems for the continuous depolymerization and valorization of lignin and low-voltage hydrogen production. A redox-active phosphomolybdic acid is used as a catalyst to depolymerize lignin with the production of aromatic compounds and extraction of electrons for hydrogen production. Individual processes for lignin depolymerization, byproduct separation, and hydrogen production with catalyst reactivation are modularized and integrated to perform the entire process in the serial flow. Consequently, this work enabled a one-flow process from biomass conversion to hydrogen gas generation under a cyclic loop. In addition, the unique advantages of the fluidic system (i.e., effective mass and heat transfer) substantially improved the yield and efficiency, leading to hydrogen production at a higher current density (20.5 mA cm-2 ) at a lower voltage (1.5 V) without oxygen evolution. This sustainable eco-chemical platform envisages scalable co-production of valuable chemicals and green hydrogen for industrial purposes in an energy-saving and safe manner.

Scalable Subsecond Synthesis of Drug Scaffolds via Aryllithium Intermediates by Numbered-up 3D-Printed Metal Microreactors.

Continuous-flow microreactors enable ultrafast chemistry; however, their small capacity restricts industrial-level productivity of pharmaceutical compounds. In this work, scale-up subsecond synthesis of drug scaffolds was achieved via a 16 numbered-up printed metal microreactor (16N-PMR) assembly to render high productivity up to 20 g for 10 min operation. Initially, ultrafast synthetic chemistry of unstable lithiated intermediates in the halogen-lithium exchange reactions of three aryl halides and subsequent reactions with diverse electrophiles were carried out using a single microreactor (SMR). Larger production of the ultrafast synthesis was achieved by devising a monolithic module of 4 numbered-up 3D-printed metal microreactor (4N-PMR) that was integrated by laminating four SMRs and four bifurcation flow distributors in a compact manner. Eventually, the 16N-PMR system for the scalable subsecond synthesis of three drug scaffolds was assembled by stacking four monolithic modules of 4N-PMRs.

Flow parallel synthesizer for multiplex synthesis of aryl diazonium libraries via efficient parameter screening.

The development of miniaturized flow platforms would enable efficient and selective synthesis of drug and lead molecules by rapidly exploring synthetic methodologies and screening for optimal conditions, progress in which could be transformative for the field. In spite of tremendous advances made in continuous flow technology, these reported flow platforms are not devised to conduct many different reactions simultaneously. Herein, we report a metal-based flow parallel synthesizer that enables multiplex synthesis of libraries of compounds and efficient screening of parameters. This miniaturized synthesizer, equipped with a unique built-in flow distributor and n number of microreactors, can execute multiple types of reactions in parallel under diverse conditions, including photochemistry. Diazonium-based reactions are explored as a test case by distributing the reagent to 16 (n = 16) capillaries to which various building blocks are supplied for the chemistry library synthesis at the optimal conditions obtained by multiplex screening of 96 different reaction variables in reaction time, concentration, and product type. The proficiency of the flow parallel synthesizer is showcased by multiplex formation of various C-C, C-N, C-X, and C-S bonds, leading to optimization of 24 different aryl diazonium chemistries.

Wet-Style Superhydrophobic Antifogging Coatings for Optical Sensors.

Transparent substrates are widely used for optical applications from lenses for personal and sports eyewear to transparent displays and sensors. While these substrates require excellent optical properties, they often suffer from a variety of environmental challenges such as excessive fogging and surface contamination. In this work, it is demonstrated that a wet-style superhydrophobic coating, which simultaneously exhibits antifogging, antireflective, and self-cleaning properties, can be prepared by pattern transferring low-surface-energy microstructures onto a heterostructured nanoscale thin film comprising polymers and silica nanoparticles. The polymer-silica nanocomposite base layer serves as a hydrophilic reservoir, guiding the water molecules to preferentially condense into this underlying region and suppress reflection, while the low-surface-energy microstructure enables contaminants adsorbed on the surface to be easily removed by rinsing with water.

Compact reaction-module on a pad for scalable flow-production of organophosphates as drug scaffolds.

Continuous pharmaceutical manufacturing receives intense attention as an alternative way to meet flexible market needs with the assurance of higher safety and quality control. Here, we report a compact reaction-module on a pad (CRP, 170 × 170 × 1.2 mm) for scale-up production of drug precursors in a continuous-flow. The CRP system was devised by stacking 9 films of the patterned polyimide to integrate micro-flow circuits, combining the functions of the even distribution of feeds, being completely mixed in less than a few milliseconds. A methodology of using a highly reactive species for the single-step synthesis of α-phosphonyloxy ketone, a drug scaffold, required the synthesis time of a few seconds in microfluidics. The fast reaction in the single CRP was capable of producing 19.2 g h-1 drug precursor, which indicates a solid step toward kilogram-scale pharmaceutical manufacturing in small footage.

Enhanced Controllability of Fries Rearrangements Using High-Resolution 3D-Printed Metal Microreactor with Circular Channel.

High-resolution 3D-printed stainless steel metal microreactors (3D-PMRs) with different cross-sectional geometry are fabricated to control ultrafast intramolecular rearrangement reactions in a comparative manner. The 3D-PMR with circular channel demonstrates the improved controllability in rapid Fries-type rearrangement reactions, because of the superior mixing efficiency to rectangular cross-section channels (250 µm × 125 µm) which is confirmed based on the computational flow dynamics simulation. Even in case of very rapid intramolecular rearrangement of sterically small acetyl group occurring in 333 µs of reaction time, the desired intermolecular reaction can outpace to the undesired intramolecular rearrangement using 3D-PMR to result in high conversion and yield.

Pore-Surface Engineering by Decorating Metal-Oxo Nodes with Phenylsilane to Give Versatile Super-Hydrophobic Metal-Organic Frameworks (MOFs).

Hydrophobization of metal-organic frameworks (MOFs) is important to push forward their practical use and thus has attracted increasing interest. In contrast to the previous reports, which mainly focused on the modification of organic ligands in MOFs, herein, we reported a novel strategy to decorate the metal-oxo nodes of MOFs with phenylsilane to afford super-hydrophobic NH2 -UiO-66(Zr), which shows highly improved base resistance and holds great promise in versatile applications, such as organic/water separation, self-cleaning, and liquid-marble fabrication. This work demonstrates the first attempt at metal-oxo node modification for super-hydrophobic MOFs, advancing a new concept in the design of MOFs with controlled wettability for practical applications.

A 3D-printed flow distributor with uniform flow rate control for multi-stacked microfluidic systems.

In the scale-up of chemical production in a microfluidic system, it is challenging to prevent flow maldistribution from a single inlet into stacked multiple microchannel exits. In the present study, a compact flow distributor equipped with a fluidic damper is developed by computational fluid dynamics (CFD) along with experimental validation. A microfluidic flow distributor, which is equipped with an optimized fluidic damper and consists of 25 exit channels, is fabricated as an integrated body using a digital light processing (DLP) type 3D printer. The 3D printed flow distributor with a CFD-optimized fluidic damper is found to achieve a low maldistribution factor (MF) of 2.2% for the average flow rate over 25 exit channels while inducing only a minor increment (<6%) in the pressure drop. A generalized manual is proposed for the design of optimal flow distributors with different scale-up dimensions. Using the manual, an optimal flow distributor with 625 stacked microchannels with a MF of only 1.2% is successfully designed. It is expected that the design manual and the rapid printing platform will allow the efficient development of multi-channel stacked micro-devices such as those in drug delivery and energy conversion systems where equidistribution of fluid flow is highly demanded.