Pure Shift NMR in Continuous Flow.

Flow NMR is an expanding analytical approach with applications that include in-line analysis for process control and optimisation, and real-time reaction monitoring. The samples monitored by flow NMR are typically mixtures that yield complex 1D H spectra. "Pure shift" NMR is a powerful approach to simplifying H NMR spectra, but its standard implementation is not compatible with continuous flow because of interference between sample motion and the position-dependent spin manipulations that are required in pure shift NMR.

Broadband ultrafast 2D NMR spectroscopy for online monitoring in continuous flow.

Flow NMR is a powerful tool to monitor chemical reactions under realistic conditions. Here, we describe ultrafast (UF) 2D NMR schemes that make it possible to acquire broadband homonuclear 2D NMR spectra in 90 seconds or less for a continuously flowing sample. An interleaved acquisition strategy is used to address the spectral width limitation of UF 2D NMR.

Signaling-specific inhibition of the CB receptor for cannabis use disorder: phase 1 and phase 2a randomized trials.

Cannabis use disorder (CUD) is widespread, and there is no pharmacotherapy to facilitate its treatment. AEF0117, the first of a new pharmacological class, is a signaling-specific inhibitor of the cannabinoid receptor 1 (CB-SSi). AEF0117 selectively inhibits a subset of intracellular effects resulting from Δ-tetrahydrocannabinol (THC) binding without modifying behavior per se.

In-line Multidimensional NMR Monitoring of Photochemical Flow Reactions.

This work demonstrates the in-line monitoring of a flow photochemical reaction using 1D and ultrafast 2D NMR methods at high magnetic field. The reaction mixture exiting the flow reactor is flown through the NMR spectrometer and directly analyzed. In the case of simple substrates, suitable information can be obtained through 1D H spectra, but for molecules of higher complexity the use of 2D experiments is key to address signal overlaps and assignment issues.

Rose Bengal Immobilized on Cellulose Paper for Sustainable Visible-Light Photocatalysis.

This work reports the heterogenization of Rose Bengal dye on simple cellulose paper sheets (Cell-RB) through copper-catalyzed azide-alkyne click ligation. The photocatalytic properties of Cell-RB under green LED irradiation were evaluated in a series of dehydrogenative transformations for the functionalization of N-aryltetrahydroisoquinolines and quinoxalin-2(1H)-ones. The excellent photocatalytic activities observed, associated to the ease of recovery with simple tweezers, highlight the strong assets of Cell-RB with respect to traditional homogeneous organic photocatalysts.

An investigation of palladium-catalyzed Stille-type cross-coupling of nitroarenes in perylenediimide series.

We report herein an unprecedented palladium-catalyzed cross-coupling reaction between mononitro-perylenediimide (PDI) and various arylstannanes. Optimized conditions developed with this Stille-type reaction allow the grafting of (hetero)aryls of various electronic nature in the bay region of PDIs. Moreover, we capitalized on the high selectivity of this cross-coupling through the desymmetrization of the dinitro-PDI substrate.

Reconfigurable Flow Platform for Automated Reagent Screening and Autonomous Optimization for Bioinspired Lignans Synthesis.

Naturally occurring benzoxanthenones, which belong to the vast family of lignans, are promising biologically relevant targets. They are biosynthetically produced by the oxidative dimerization of 2-propenyl phenols. In this manuscript, we disclose a powerful automated flow-based strategy for identifying and optimizing a cobalt-catalyzed oxidizing system for the bioinspired dimerization of 2-propenyl phenols.

Hydrophobic Covalent Patterns on Cellulose Paper through Photothiol-X Ligations.

In the current study, we introduce photothiol-X chemistry as a powerful method to create hydrophobic patterns covalently grafted to the surface of cellulose paper. The general strategy builds on the use of a cellulose-based molecular printboard featuring disulfide functions which upon spatiocontrolled light irradiation at 365 nm allows robust photothiol-X ligations with hydrophobic moieties. A screening of structurally diverse molecular architectures as hydrophobic coating was conducted, and the most impressive result obtained with cholesterol moieties allows the creation of spatially well-resolved hydrophobic patterns with a contact angle of 140.

Heptylmannose-functionalized cellulose for the binding and specific detection of pathogenic E. coli.

We developed a chemical method to covalently functionalize cellulose nanofibers and cellulose paper with mannoside ligands displaying a strong affinity for the FimH adhesin from pathogenic E. coli strains. Mannose-grafted cellulose proved efficient to selectively bind FimH lectin and discriminate pathogenic E.

A fully bio-sourced adsorbent of heavy metals in water fabricated by immobilization of quinine on cellulose paper.

The fabrication of a fully bio-sourced adsorbent of Cd(II) by covalent immobilization of quinine on cellulose paper is described. The double bond of commercially available quinine was converted to a terminal alkyne function which was reacted with cellulose paper, chemically modified with azide functions, through a 1,3-dipolar cycloaddition, leading to Cell-Quin. The adsorption efficiency of Cell-Quin was investigated to determine the optimal pH, contact time and dose of adsorbent, ultimately leading to high levels of removal.

Biaryl synthesis with arenediazonium salts: cross-coupling, CH-arylation and annulation reactions.

The rich legacy of arenediazonium salts in the synthesis of unsymmetrical biaryls, built around the seminal works of Pschorr, Gomberg and Bachmann more than a century ago, continues to make important contributions at various evolutionary stages of modern biaryl synthesis. Based on in-depth mechanistic analysis and design of novel pathways and reaction conditions, the scope of biaryl synthesis with arenediazonium salts has enormously expanded in recent years through applications of transition metal/photoredox-catalysed cross-coupling, thermal/photosensitized radical chain CH-arylation of (hetero)arenes and arylative radical annulation reactions with alkynes. These recent developments have provided facile synthetic access to a wide variety of unsymmetrical biaryls of pharmaceutical, agrochemical and optoelectronic importance with green scale-up options and created opportunities for late-stage modification of peptides, nucleosides, carbon nanotubes and electrodes, the details of which are captured in this review.

An Autonomous Self-Optimizing Flow Reactor for the Synthesis of Natural Product Carpanone.

A modular autonomous flow reactor combining monitoring technologies with a feedback algorithm is presented for the synthesis of the natural product carpanone. The autonomous self-optimizing system, controlled via MATLAB, was designed as a flexible platform enabling an adaptation of the experimental setup to the specificity of the chemical transformation to be optimized. The reaction monitoring uses either online high pressure liquid chromatography (HPLC) or in-line benchtop nuclear magnetic resonance (NMR) spectroscopy.

Oxidative Neutralization of Mustard-Gas Simulants in an On-Board Flow Device with In-Line NMR Monitoring.

The fast and effective neutralization of the mustard-gas simulant 2-chloroethyl ethyl sulfide (CEES) using a simple and portable continuous flow device is reported. Neutralization takes place through a fully selective sulfoxidation by a stable source of hydrogen peroxide (alcoholic solution of urea-H O adduct/MeSO H freshly prepared). The reaction progress can be monitored with an in-line benchtop NMR spectrometer, allowing a real-time adjustment of reaction conditions.

Harnessing the Dual Properties of Thiol-Grafted Cellulose Paper for Click Reactions: A Powerful Reducing Agent and Adsorbent for Cu.

A new approach exploiting the dual properties of thiol-grafted cellulose paper for promoting copper-catalyzed [3+2]-cycloadditions of organic azides with alkynes and adsorbing residual copper species in solution was developed. The thiol-grafted cellulose paper, used as a paper strip, effects the reduction of Cu to catalytically active Cu and acts as a powerful adsorbent for copper, thereby facilitating the work-up process and leaving the crude mixture almost free of copper residues after a single filtration.

A paper-based biomimetic device for the reduction of Cu(ii) to Cu(i) - application to the sensing of Cu(ii).

A biomimetic device for the reduction of Cu(ii) to Cu(i) consisting of thioglycolic acid covalently grafted to cellulose paper was developed. The device displays exceptionally fast reducing properties allowing the reduction of Cu(ii) in seconds and the formation of deeply colored Cu(i)-SCH2R complexes onto the cellulose paper. This biomimetic and biomaterial-based concept was exploited for the detection of copper in water samples with a limit of detection as low as 2 ppm.

Cu and Cu-Based Nanoparticles: Synthesis and Applications in Catalysis.

The applications of copper (Cu) and Cu-based nanoparticles, which are based on the earth-abundant and inexpensive copper metal, have generated a great deal of interest in recent years, especially in the field of catalysis. The possible modification of the chemical and physical properties of these nanoparticles using different synthetic strategies and conditions and/or via postsynthetic chemical treatments has been largely responsible for the rapid growth of interest in these nanomaterials and their applications in catalysis. In addition, the design and development of novel support and/or multimetallic systems (e.

Chemically-modified cellulose paper as smart sensor device for colorimetric and optical detection of hydrogen sulfate in water.

A portable, recyclable and highly selective paper-based sensor device for the colorimetric and optical detection of hydrogen sulfate anions in water was developed. The detection system features a rhodamine-based sensor covalently grafted onto the highly hydrophilic surface of cellulose paper.

Real-time reaction monitoring by ultrafast 2D NMR on a benchtop spectrometer.

Reaction monitoring is widely used to follow chemical processes in a broad range of application fields. Recently, the development of robust benchtop NMR spectrometers has brought NMR under the fume hood, making it possible to monitor chemical reactions in a safe and accessible environment. However, these low-field NMR approaches suffer from limited resolution leading to strong peak overlaps, which can limit their application range.

Continuous-flow Heck-Matsuda reaction: homogeneous versus heterogeneous palladium catalysts.

This study describes extensive investigations of the Heck-Matsuda reaction carried out by continuous-flow chemistry between aryl diazonium salts generated in situ and methyl acrylate. Our optimized procedures enable sequential aniline diazotization/palladium-catalyzed Heck-Matsuda reaction using either Pd(OAc)2 or PdEnCat 30 as respectively a homogeneous or a heterogeneous source of palladium. This safe chemistry that does not require the handling of hazardous aryl diazonium salts involves inexpensive reagents and solvents, under ligand- and base-free conditions.

Design, synthesis and biological evaluation of Pontin ATPase inhibitors through a molecular docking approach.

A virtual screening strategy, through molecular docking, for the elaboration of an electronic library of Pontin inhibitors has resulted in the identification of two original scaffolds. The chemical synthesis of four candidates allowed extensive biological evaluations for their anticancer activity. Two compounds displayed an effect on Pontin ATPase activity, and one of them also exhibited a noticeable effect on cell growth.

Stabilisation of carbon-supported palladium nanoparticles through the formation of an alloy with gold: application to the Sonogashira reaction.

Oh my Gold! Gold atoms stabilise catalytically active palladium nanoparticles when engaged in an alloy heterogenised on carbon. The increased durability makes the Pd-Au/C catalyst more recyclable than the gold-free Pd/C catalyst for the Sonogashira reaction.

Copper-catalyzed free-radical C-H arylation of pyrroles.

A room temperature copper-catalyzed radical arylation of pyrroles with anilines, through in situ generated aryl diazonium salts, has been developed under neutral conditions. Experimental and theoretical studies explain the crucial role of CaCO3 and the high regioselectivity observed.

Practical synthesis of indoles and benzofurans in water using a heterogeneous bimetallic catalyst.

This paper describes the preparation of indoles, azaindoles and benzofurans in pure water by using a new heterogeneous Pd-Cu/C catalyst through a cascade Sonogashira alkynylation-cyclization sequence. Details of the optimization studies and the substrate scope are discussed. This procedure allows the preparation of heterocycles with good yields and is tolerant to a wide variety of functional groups.

Chelation-assisted cross-coupling of anilines through in situ activation as diazonium salts with boronic acids under ligand-, base-, and salt-free conditions.

We describe the coupling of anilines with aryl boronic acids, under ligand-, base-, and salt-free conditions at room temperature. This new reaction proceeds through the formation of an aryl palladium alkoxo complex, which allows the transmetalation step with aryl boronic acids without any external base. Importantly, this sustainable procedure generates only environmentally friendly byproducts such as tBuOH, H2O, N2, and B(OH)3.