2-Diphenylphosphinomethyl-3-methylpyrazine

The lateral metalation-electrophilic trapping reaction of alkyl-substituted pyrazines has always been challenging and poorly regioselective, with the corresponding derivatives often being isolated in moderate yield. In this contribution, we first report on the preparation of an unsymmetrically-substituted pyrazine, that is 2-diphenylphosphinomethyl-3-methylpyrazine, by subjecting to metalation with n-BuLi the commercially available 2,3-dimethylpyrazine, followed by interception of the putative lithiated benzyl-type intermediate with Ph2PCl. Such a functionalization has been successfully carried out in the absence of additional ligands, working either in THF at −78 °C or in a more environmentally friendly solvent like cyclopentyl methyl ether at 0 °C, with the desired phosphine derivative being isolated in 70–85% yield. The newly synthesized adduct has been fully characterized by means of multinuclear magnetic resonance spectroscopic techniques, and also by preparing a selenium derivative, which furnished single crystals that were suitable for X-ray analysis

Oxidized Alginate Dopamine Conjugate: In Vitro Characterization for Nose‐to‐Brain Delivery Application

Background: The blood–brain barrier (BBB) bypass of dopamine (DA) is still a challenge for supplying it to the neurons of Substantia Nigra mainly affected by Parkinson disease. DA prodrugs have been studied to cross the BBB, overcoming the limitations of DA hydrophilicity. Therefore, the aim of this work is the synthesis and preliminary characterization of an oxidized alginate-dopamine (AlgOX-DA) conjugate conceived for DA nose-to-brain delivery. Methods: A Schiff base was designed to connect oxidized polymeric backbone to DA and both AlgOX and AlgOX-DA were characterized in terms of Raman, XPS, FT-IR, and 1H- NMR spectroscopies, as well as in vitro mucoadhesive and release tests. Results: Data demonstrated that AlgOX-DA was the most mucoadhesive material among the tested ones and it released the neurotransmitter in simulated nasal fluid and in low amounts in phosphate buffer saline. Results also demonstrated the capability of scanning near-field optical microscopy to study the structural and fluorescence properties of AlgOX, fluorescently labeled with fluorescein isothiocyanate microstructures. Interestingly, in SH-SY5Y neuroblastoma cell line up to 100 μg/mL, no toxic effect was derived from AlgOX and AlgOX-DA in 24 h. Conclusions: Overall, the in vitro performances of AlgOX and AlgOX-DA conjugates seem to encourage further ex vivo and in vivo studies in view of nose-to-brain administratio

Water and Sodium Chloride: Essential Ingredients for Robust and Fast Pd-catalysed Cross-coupling Reactions between Organolithiums and (Hetero)aryl halides

Direct palladium-catalysed cross-couplings between organolithiums and (hetero)aryl halides (Br, Cl) proceed fast, cleanly and selectively at room temperature in air, with water as the only reaction medium and in the presence of NaCl as a cheap additive. Under optimised reaction conditions, a water-accelerated catalysis is responsible for furnishing Csp3–Csp2, Csp2–Csp2, and Csp–Csp2 cross-coupled products, competitively with protonolysis, within a 20 s reaction time, in yields of up to 99%, and in the absence of undesired dehalogenated/homocoupling side-products even if it starts from challenging secondary organolithiums. It is worth noting that the proposed protocol is scalable and the catalyst and water can easily and successfully be recycled up to 10 times, with an E-factor as low as 7.35

Deep Eutectic Solvents in Solar Energy Technologies

Deep Eutectic Solvents (DESs) have been widely used in many fields to exploit their ecofriendly characteristics, from green synthetic procedures to environmentally benign industrial methods. In contrast, their application in emerging solar technologies, where the abundant and clean solar energy is used to properly respond to most important societal needs, is still relatively scarce. This represents a strong limitation since many solar devices make use of polluting or toxic components, thus seriously hampering their eco-friendly nature. Herein, we review the literature, mainly published in the last few years, on the use of DESs in representative solar technologies, from solar plants to last generation photovoltaics, featuring not only their passive role as green solvents, but also their active behavior arising from their peculiar chemical nature. This collection highlights the increasing and valuable role played by DESs in solar technologies, in the fulfillment of green chemistry requirements and for performance enhancement, in particular in terms of long-term temporal stability

Introducing Water and Deep Eutectic Solvents in Organosodium Chemistry: Chemoselective Nucleophilic Functionalizations in Air

: Advancing the development of perfecting the use of polar organometallics in bio-inspired solvents, we report on the effective generation in batch of organosodium compounds, by the oxidative addition of a C-Cl bond to sodium, a halogen/sodium exchange, or by direct sodiation, when using sodium bricks or neopentylsodium in hexane as sodium sources. C(sp3)-, C(sp2)-, and C(sp)-hybridized alkyl and (hetero)aryl sodiated species have been chemoselectively trapped (in competition with protonolysis), with a variety of electrophiles when working "on water", or in biodegradable choline chloride/urea or L-proline/glycerol eutectic mixtures, under hydrous conditions and at room temperature. Additional benefits include a very short reaction time (20 s), a wide substrate scope, and good to excellent yields (up to 98%) of the desired adducts. The practicality of the proposed protocol was demonstrated by setting up a sodium-mediated multigram-scale synthesis of the anticholinergic drug orphenadrine

Ligand‐free Copper‐Catalyzed Ullmann‐type C–O Bond Formation in Non‐innocent Deep Eutectic Solvents under Aerobic Conditions

An efficient and novel protocol was developed for a Cu-catalyzed Ullmann-type aryl alkyl ether synthesis by reacting various (hetero)aryl halides (Cl, Br, I) with alcohols as active components of environmentally benign choline chloride-based eutectic mixtures. Under optimized conditions, the reaction proceeds under mild conditions (80 °C) in air, in the absence of additional ligands, with a catalyst [Cu(I) or Cu(II) species] loading up to 5 mol% and K 2 CO 3 as the base, providing the desired aryloxy derivatives in up to 98% yield. The potential application of the methodology is demonstrated in the valorization of cheap, easily available, and naturally occurring polyols (e.g., glycerol) for the synthesis of some pharmacologically active aryloxypropanediols (Guaiphenesin, Mephenesin and Chlorphenesin) on a 2-gram scale in 70–96% yield. The catalyst, the base, and the DES could easily and successfully be recycled up to seven times with an E-factor as low as 5.7