Organic redox species are finding uses in numerous research and development applications, such as electrochemical sensors, batteries, and production of chemicals. This paper presents a synthesis pathway of a redox-active liquid of 2,3,5,6-tetraallylbenzene-1,4-diol. The synthesis of 2,3,5,6-tetraallylbenzene-1,4-diol was found repeatable at approximately 60 g scale, with a total conversion of 92% across four synthesis steps. High purity was achieved with no further purification. The intermediates and compounds were characterized using attenuated total reflectance infrared spectroscopy, proton nuclear magnetic resonance, differential scanning calorimetry, thermogravimetric analysis, cyclic voltammetry, rotating disk electrode voltammetry, density, and viscosity measurements. The structural characterization verified the structure of 2,3,5,6-tetraallylbenzene-1,4-diol. Electrochemical characterization revealed a quasi-reversible response, a diffusion coefficient similar to the diffusion coefficient of hydroquinone.

Glycolaldehyde, produced from cracking of glucose, was tested as a substitute for formaldehyde in urea-based wood adhesives. Initially, different parameters (water content, aldehyde/urea-ratio, curing temperature, and time) were screened to identify the optimal curing conditions providing the highest bond strength. Afterwards, the system was reformulated as a 2-component system and compared to a ureaformaldehyde 2-component system, which showed a comparatively low strength of the resulting resin. Different hardeners were tested, and AlCl3 showed an 80% increase in bond strength for the resin compared to NH4Cl. Infrared and nuclear magnetic resonance analyses were performed to ensure formation of the desired aminal bond network, which showed that the hardener was essential for proper curing of the resin. Finally, a urea-glycolaldehyde-formaldehyde resin was tested that further indicated major differences between the reactivity of formaldehyde and glycolaldehyde.

Polyurethane (PU) is a highly engineered and cross -linked polymer found in a plethora of materials such as mattresses, shoes, windmills, and insulation of refrigerating appliances and buildings. Because of PU's inherent stability, chemical recycling is difficult and often affords a secondary feed with different characteristics and properties compared to the original input. In this work, a simple chemical recycling of PU via a solvolysis process using tertamyl alcohol both as the solvent and reagent is demonstrated. The devised methodology is showcased for the deconstruction of 20 different PU materials with examples of all four cornerstones of PU (rigid solid, rigid foamed, flexible foamed, and flexible solid). The solvolysis affords both polyol and dianiline fractions, constituting monomeric precursors of PU. The methodology is used for the depolymerization of 50 g flexible PU foam affording a polyol within specification of the original virgin polyol (OH value) and an aniline fraction isolated as the precipitated di-HCl salt with a combined mass recovery of 89 wt%. As the solvolysis process provides access to both the polyol and the aniline precursors of the original isocyanate of PU, the procedure presented in this study could pave the way toward a viable circular economy for PU. A further potential utilization of the method is showcased by valorization of a waste stream from split-phase glycolysis, which is another promising method for recovering polyol from flexible PU foam. Finally, preliminary mechanistic investigations are undertaken to probe the intriguing utility of a hindered tertiary alcohol in a solvolysis procedure.

Polyurethane (PU) is a highly valued polymer prepared from diisocyanates and polyols, and it is used in everyday products, such as shoe soles, mattresses, and insulation materials, but also for the construction of sophisticated parts of medical devices, wind turbine blades, aircrafts, and spacecrafts, to name a few. As PU is most commonly used as a thermoset polymer composed of cross-linked structures, its recycling is complicated and inefficient, leading to increasing PU waste accumulating every year. Catalytic hydrogenation represents an atom-efficient means for the deconstruction of polyurethanes, but so far the identification of an efficient catalyst for the disassembly of real-life and end-of-life PU samples has not been demonstrated. In this work, we reveal that a commercially available catalyst, Ir-iPrMACHO, under 30 bar H2 and 150–180 °C, is a general catalyst for the effective hydrogenation of the four cornerstones of PU: flexible solid, flexible foamed, rigid solid, and rigid foamed, leading to the isolation of aromatic amines and a polyol fraction. For the first time, a variety of commercial PU materials, including examples of foams, inline skating wheels, shoe soles, and insulation materials, has been deconstructed into the two fractions. Most desirable, our reaction conditions include the use of isopropyl alcohol as a representative of a green solvent. It is speculated that a partial glycolysis at the surface of the PU particles is taking place in this solvent and reaction temperatures in the presence of catalytic amounts of base. As such a more efficient hydrogenation of the solubilized PU fragments in isopropyl alcohol becomes possible. As the isolated anilines are precursors to the original isocyanate building blocks, and methods for their conversion are well-known, the work reported in this paper provides a realistic indication of a potential circular plastic economy solution for PU. Preliminary experiments were also undertaken applying Mn-iPrMACHO for the deconstruction of a commercial flexible PU foam. Although successful, more forcing conditions were required than those when applying Ir-iPrMACHO.

A copper-catalyzed decarboxylative trifluoromethylation of (hetero)aromatic iodides has been developed. Importantly, this new copper-catalyzed reaction operates in the absence of any ligands and metal additives. The protocol shows good functional group tolerance and is compatible with heteroaromatic systems. The reaction proved scalable to a 15 mmol scale with increased yield. Finally, late-stage installation of the trifluoromethyl functionality afforded the N-trifluoroacetamide variant of the antidepressant agent, Prozac, demonstrating the applicability of the developed method.

The trifluoromethyl group is an important functionality that can be found in many pharmaceuticals and agrochemicals, being strategically installed to fine-tune metabolic and chemical properties of these bioactive molecules. However, the incorporation of the trifluoromethyl group in aromatic compounds is often costly in fluorinating agents or requires the use of (super)stoichiometric transition metals.

Bench-stable tablets (COtabs) have been developed for the rapid and safe production of carbon monoxide. The tablets can be made in less than 5 min without the use of a glovebox and only require a stock solution of an amine base to liberate a specific quantity of CO in a two-chamber system. The COtabs were tested in five different carbonylation reactions and provided similar yields compared to literature procedures. Finally, a gram-scale reaction was conducted, as well as 13C-isotope labeling of the anticancer drug, olaparib.

Carbon monoxide represents the most important C1-building block for the chemical industry, both for the production of bulk and fine chemicals, but also for synthetic fuels. Yet its toxicity and subsequently its cautious handling have limited its applications in medicinal chemistry research and in particular for the synthesis of pharmaceutically relevant molecules. Recent years have nevertheless witnessed a considerable headway on the development of carbon monoxide surrogates and reactor systems, which provide an ideal setting for performing carbonylation chemistry with stoichiometric and substoichiometric carbon monoxide. Such setups are particularly ideal for the introduction of isotope labels such as carbon-11, carbon-13, and carbon-14 into bioactive compounds. This review summarizes this growing field and examines the large number of carbonylation reactions that can be exploited for the introduction of a carbon isotope.

A simple to prepare, dry and handle packed bed reactor carrying CsF on CaF2, towards nucleophilic fluorinations in continuous flow, is reported. The reactor also proved adaptable for silyl-ether deprotection and trifluoromethylations with Ruppert's reagent. The study includes reactor stability and scale-up investigations.

A simple setup has been devised to facilitate safer transfer of air-sensitive and pyrophoric reagents from Sure/Seal bottles in a fume hood setting. The setup is composed of three parts; a sealed transfer vial, a custom bottle cap for transfer vial alignment, and a metal clip. All of the needed parts are constructed from standard laboratory equipment and by 3D printing. Titration of tert-butyllithium was used as an example of safe transfer of a highly pyrophoric reagent, and an instructional video has been prepared.

Carbon monoxide represents the most important C1‐building block for the chemical industry, both for the production of bulk and fine chemicals, but also for synthetic fuels. Yet its toxicity and subsequently its cautious handling have limited its applications in medicinal chemistry research and in particular for the synthesis of pharmaceutically relevant molecules. Recent years have nevertheless witnessed a considerable headway on the development of carbon monoxide surrogates and reactor systems, which provide an ideal setting for performing carbonylation chemistry with stoichiometric and substoichiometric carbon monoxide. Such setups are particularly ideal for the introduction of isotope labels such as carbon‐11, carbon‐13, and carbon‐14 into bioactive compounds. This review summarizes this growing field and examines the large number of carbonylation reactions that can be exploited for the introduction of a carbon isotope.

Conditions for the Morita-Baylis-Hillman reaction were developed under continuous flow using a packed bed reactor carrying 4-(dimethylamino)pyridine immobilized on silica. High reaction rates were obtained, as the packed bed reactor mimics super-stoichiometric catalyst loadings for the passing reaction mixture. Catalyst deactivation was circumvented by avoiding acrylate esters as the reaction partners. The developed flow protocol provided all desired Morita-Baylis-Hillman products in yields attaining 95% with typical retention times between just 30 and 60 min. Precise control of the retention time proved imperative for one example, in which optimal yield was attained in just 10 min, while outpacing sideproduct formation. Finally, a scale-out study was performed proving high stability of the packed bed reactor setup and catalyst for more than 20 h of operation.

Two protocols for the organocatalyzed decarboxylative trichloromethylation of Morita-Baylis-Hillman (MBH) substrates have been developed. Applying sodium trichloroacetate, as the trichloromethyl anion precursor, in combination with an organocatalyst and acetylated MBH-al-cohols, the desired trichloromethylated products were obtained in good yields at room temperature in batch. The method was next extrapolated into a two-step continuous flow protocol, starting directly from the MBH alcohols, in combination with tributylamine acting both as base and catalyst. The flow process proved superior to the batch approach, reducing the reaction time from 16 hours to only 20 minutes, with increased yields for all investigated entries. Two examples were also taken to scale-up in flow producing more than 10 grams of both trichloromethylated targets. Finally, substitution of the organocatalyst to (DHQ)(2)PHAL or (DHQD)(2)PHAL induced chiral transfer to the generated stereocenter in the reaction attaining selectivities with nearly 90% ee.

A new synthetic route to the Tau binder, THK-523, is disclosed herein, which can easily be adapted to 13 C- and D-isotope labeling. The synthesis proceeds via two key reactions, namely, a Pd-catalyzed carbonylative Sonogashira coupling and a reductive ring-closing step with hydrogen or deuterium gas. By carrying out these reactions in a 2-chamber reactor we reported previously, ex situ-generated carbon monoxide and hydrogen/deuterium can be applied in stoichiometric quantities, thereby facilitating isotope labeling of this Tau-binding compound. Iridium-catalyzed hydrogen isotope exchange (HIE) reactions were performed on THK-523 and its 13 C-labeled analog providing access to 4 additional analogues labeled with deuterium as well. Finally, by applying a Buchwald-Hartwig coupling, we were able to prepare a 15 N-THK-523 variant with the isotope label in the quinoline ring system.

Carbon Dioxide Activation Center (CADIAC Department of Chemistry, Aarhus Universi Denmark. E-mail: ts@chem.au.dk Center for Materials Crystallography, Department of Chemistry, Aarhus Univers Denmark Haldor Topsøe A/S, New Business R&D, Ny Carbon Dioxide Activation Center (CADIAC Biological and Chemical Engineering, Depa Finlandsgade 22, 8200 Aarhus N, Denmark † Electronic supplementary information ( For ESI and crystallographic data in CI 10.1039/c7sc03912c Cite this: Chem. Sci., 2017, 8, 8094

A suitcase sized mobile reactor unit (MRU) weighing in at less than 10 kg was designed for laboratory scale transfer hydrogenations in continuous flow. Simple cyclohexene and a cosolvent in combination with a palladium-on-charcoal packed bed reactor provided a setup with isolation of nearly all products without the need for further purification. Several functional groups including olefins, triple bonds, nitro-groups, carbonyls, and so forth were effectively reduced with retention times as low as 2 min. Additionally, standard protection groups such as Cbz, benzyl, and allyl ether or esters were removed in high yields. To prove the flexibility of the setup an example of the Mizoroki–Heck reaction was also performed on the MRU. Finally, two scale-up transfer hydrogenation experiments were performed affording isolation of the desired target compounds in 0.5 and 0.8 mol scales with less than 4 h of continuous operation on the MRU.

Structural characterizations of three different solidgas reaction products, recently obtained from abraded solid-state silicate free radicals reacting with two isotopically enriched methane gases, (CH4)-C-13 and CD4 (a possible sink for methane on MARS) and with (CO2)-C-13, are derived from various dynamic solid-state NMR experiments. These include cross-polarization/depolarization zero-cross times (ZCTs), variable temperature (VT) NMR to study 3-site jump CH3/CD3 activation energies (E-a), and (CO2)-C-13/(CH3)-C-13 molecular species as a spy to determine the approximate diameters for the channel structures for some of these structures. Literature Ea data indicate that l-alanine and 4-CH3-phenanthrene exhibit the highest known Ea values (= 2022.6 kJ/mol) for CH3 3-site jump motions. The ZCTs for these two compounds are 120 and 162 mu s, respectively, indicative of the high E-a values for CH3/CD3 groups. Determination of Ea for 4-CD3-phenanthrene by low-temperature 2H MAS NMR experiments supplemented the previously reported liquid-state E-a value (E-a = 21 kJ/mol) for 4-CH3-phenanthrene. Finally, such experiments also revealed the structural difference for the free-radical reaction products with (CH4)-C-13 and CD4, i.e, a change from helical to chain structure.

We demonstrate how hydrogen cyanide can be exploited for the cyanation of aryl bromides with Pd-catalysis.

A longstanding challenge in production chemistry is the development of catalytic methods for the transformation of carbon dioxide into useful chemicals. Silane and borane promoted reductions can be fined-tuned to provide a number of C1-building blocks under mild conditions, but these approaches are limited because of the production of stoichiometric waste compounds. Here we report on the conversion of CO2 with diaryldisilanes, which through cooperative redox activation generate carbon monoxide and a diaryldisiloxane that actively participate in a palladium-catalysed carbonylative Hiyama-Denmark coupling for the synthesis of an array of pharmaceutically relevant diarylketones. Thus the disilane reagent not only serves as the oxygen abstracting agent from CO2, but the silicon-containing 'waste', produced through oxygen insertion into the Si-Si bond, participates as a reagent for the transmetalation step in the carbonylative coupling. Hence this concept of cooperative redox activation opens up for new avenues in the conversion of CO2.

We report on a three-component palladium-catalyzed coupling strategy for accessing a wide range of 1,4-diketones, which represent important precursors to heterocycles. Our method relies on a carbonylative Heck reaction employing substituted allylic alcohols, aryl iodides, and carbon monoxide. The reaction conditions are mild and do not require high CO pressure, and a wide functional group tolerance is revealed, providing the desired 1,4-diketones in moderate to good yields. Furthermore, the methodology is adaptable to the selective installment of C-13-carbon isotopes at either one or both of the carbonyl positions.