A sustainable and scalable protocol for synthesizing variously functionalized sulfonamides, from amines and sulfonyl chlorides, has been developed using environmentally responsible and reusable choline chloride (ChCl)-based deep eutectic solvents (DESs). In ChCl/glycerol (1 : 2 mol mol) and ChCl/urea (1 : 2 mol mol), these reactions yield up to 97 % under aerobic conditions at ambient temperature within 2-12 h. The practicality of the method is exemplified by the sustainable synthesis of an FFA4 agonist and a key building block en route to anti-Alzheimer drug BMS-299897.
View Article and Find Full Text PDFAn enhanced, sustainable, and efficient method for synthesizing tacrine, achieving a 98% yield, has been developed by replacing volatile organic compounds with more eco-friendly solvents such as deep eutectic solvent (DESs). The optimized protocol scales easily to 3 g of substrate without yield loss and extends successfully to tacrine derivatives with reduced hepatotoxicity. Particularly notable is the synthesis of novel triazole-based derivatives, yielding 90-95%, by integrating an in situ preparation of aryl azides in DESs with -propargyl-substituted tacrine derivatives.
View Article and Find Full Text PDFA new scalable synthesis of ()-α,β-unsaturated esters has been developed using protic, non-toxic, and biodegradable deep eutectic solvents through the Horner-Wadsworth-Emmons reaction between triethyl phosphonates and (hetero)aromatic carbonyl compounds, encompassing electron-withdrawing and electron-donating groups. Stereoselective preparation of disubstituted or trisubstituted ethyl cinnamate derivatives is achieved in the presence of LiOH, KCO, or DBU as bases, at room temperature and under air. Demonstrated with the synthesis of ()-ethyl 3-(4-bromophenyl)acrylate, the same eutectic mixture (choline chloride/urea) proved to be reusable for three consecutive runs.
View Article and Find Full Text PDFWith respect to the Parkinson's disease (PD), herein, we aimed at synthetizing and characterizing two novel macromolecular conjugates where dopamine (DA) was linked to N,O-carboxymethyl chitosan or O-carboxymethyl chitosan, being both conjugates obtained from an organic solvent free synthetic procedure. They were characterized by FT-IR, H NMR spectroscopies, whereas thermal analysis (including Differential Scanning Calorimetry and Thermal Gravimetric Analysis) revealed good stability of the two conjugates after exposure at temperatures close to 300 °C. Release studies in simulated nasal fluid elucidated that a faster release occurred since O-carboxymethyl chitosan-DA conjugate maybe due to the less steric hindrance exerted by the polymeric moiety.
View Article and Find Full Text PDFBacillus subtilis is a Gram-positive, spore-forming bacterium with a versatile and adaptable metabolism, which makes it a viable cell factory for microbial production. Electroactivity has recently been identified as a cellular characteristic linked with the metabolic activity of B. subtilis.
View Article and Find Full Text PDFOwing to a growing awareness towards environmental impact, the search for "greener", safer, and cost-effective solvents able to replace petroleum-derived solvents has never been greater today. In this context, the use of environmentally responsible solvents like water and the so-called deep eutectic solvents (DESs), constructed from bio-based compounds, has recently experienced important growth in several fields of sciences. This short review highlights the key features of the chemistry of water and (hydrated) DESs when applied to metal- and biocatalyzed transformations as well as to the synthesis of active pharmaceutical ingredients (APIs) and other biologically relevant compounds by providing, through discussion of all relevant literature over the past five years, a comparison of the outcomes of the reactions when carried out in one or the other solvent.
View Article and Find Full Text PDFWe report the first transition metal catalyst- and ligand-free conjugate addition of lithium tetraorganozincates (R ZnLi ) to nitroolefins. Displaying enhanced nucleophilicity combined with unique chemoselectivity and functional group tolerance, homoleptic aliphatic and aromatic R ZnLi provide access to valuable nitroalkanes in up to 98 % yield under mild conditions (0 °C) and short reaction time (30 min). This is particularly remarkable when employing β-nitroacrylates and β-nitroenones, where despite the presence of other electrophilic groups, selective 1,4 addition to the C=C is preferred.
View Article and Find Full Text PDFThe CuI-catalyzed Ullmann amine cross-coupling between (hetero)aryl halides (Br, I) and aromatic and aliphatic amines has been accomplished in deep eutectic solvents as environmentally benign and recycling reaction media. Under optimized conditions, the reaction proceeds smoothly under mild conditions (60-100°C) in air, in the absence of ligands, with a catalyst (CuI) loading of 10 mol% and KCO (aliphatic primary and secondary amines) or -BuOK (aromatic amines) as the base. A variety of amines have been synthesized in yields up to 98% with a broad substrate scope.
View Article and Find Full Text PDFDirected ortho metalation (DoM) or nucleophilic acyl substitution (SAc) can be efficiently programmed on the same aromatic carboxylic acid amide, in a choline chloride-based eutectic mixture, by simply switching the nature of the organolithium reagent. Telescoped, one-pot ortho-lithiation/Suzuki-Miyaura cross-couplings have also been demonstrated for the first time in Deep Eutectic Solvents.
View Article and Find Full Text PDFElectrolytically tunable graphene "building blocks" for reconfigurable and optically transparent microwave surfaces and absorbers have been designed and fabricated by exploiting Deep Eutectic Solvents (DESs). DESs have been first explored as electrolytic and environmentally friendly media for tuning sheet resistance and Fermi level of graphene together with its microwave response (reflection, transmission and absorption). We consider the tunability of the reconfigurable surfaces in terms of transmittance, absorption and reflectance, respectively, over the X and Ku bands when the gate voltage is varied in the -1.
View Article and Find Full Text PDFDirect palladium-catalysed cross-couplings between organolithium reagents 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 C(sp )-C(sp ), C(sp )-C(sp ), and C(sp)-C(sp ) cross-coupled products, in competition with protonolysis, within a reaction time of 20 s, in yields of up to 99 %, and in the absence of undesired dehalogenated/homocoupling side products even when challenging secondary organolithiums serve as the starting material. 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.
View Article and Find Full Text PDFThe use of a hydrophobic eutectic solvent based on dl-menthol and a naturally occurring acid such as acetic acid has been tested as an eco-friendly electrolyte medium in dye-sensitized solar cells. In the presence of a de-aggregating agent and a representative hydrophobic organic photosensitizer, the corresponding devices displayed relatively good power conversion efficiencies in very thin active layers. In particular, the higher cell photovoltage detected in comparison to devices based on toxic and volatile organic compounds may stem from a more efficient interface interaction, as suggested by electrochemical impedance spectroscopy studies showing greater charge recombination resistance and electron lifetime.
View Article and Find Full Text PDFA few symptomatic drugs are currently available for Alzheimer's Disease (AD) therapy, but these molecules are only able to temporary improve the cognitive capacity of the patients if administered in the first stages of the pathology. Recently, important advances have been achieved about the knowledge of this complex condition, which is now considered a multi-factorial disease. Researchers are, thus, more oriented toward the preparation of molecules being able to contemporaneously act on different pathological features.
View Article and Find Full Text PDFIn contrast to classic methods carried out under inert atmospheres with dry volatile organic solvents and often low temperatures, the addition of highly polar organometallic compounds to non-activated imines and nitriles proceeds quickly, efficiently, and chemoselectively with a broad range of substrates at room temperature and under air with water as the only reaction medium. Secondary amines and tertiary carbinamines are furnished in yields of up to and over 99 %. The significant solvent D/H isotope effect observed for the on-water nucleophilic additions of organolithium compounds to imines suggests that the on-water catalysis arises from proton transfer across the organic-water interface.
View Article and Find Full Text PDFAn unprecedented, environmentally friendly, and faster method for the determination of Ochratoxin A (OTA) (a mycotoxin produced by several species of and and largely widespread in nature, in wheat and derived products) has, for the first time, been set up and validated using choline chloride (ChCl)-based deep eutectic solvents (DESs) (e.g., ChCl/glycerol (1:2) and ChCl/ urea (1:2) up to 40% (/) water) as privileged, green, and biodegradable extraction solvents.
View Article and Find Full Text PDFRegio- and stereo-selective reduction of substituted 1,3-aryldiketones, investigated in the presence of different whole cell microorganisms, was found to afford β-hydroxyketones or 1,3-diols in very good yields (up to 95%) and enantiomeric excesses (up to 96%). The enantiomerically enriched aldols, obtained with the opposite stereo-preference by baker's yeast and Lactobacillus reuteri DSM 20016 bioreduction, could then be diastereoselectively transformed into optically active syn- or anti-1,3-diols by a careful choice of the chemical reducing agent (diastereomeric ratio up to 98 : 2). The latter, in turn, were stereospecifically cyclized into the corresponding oxetanes in 43-98% yields and in up to 94% ee, thereby giving a diverse selection of stereo-defined 2,4-disubstituted aryloxetanes.
View Article and Find Full Text PDFA high-yield one-pot two-step synthesis of 2-aminoimidazoles (2-AI), exploiting an under-air heterocyclodehydration process between α-chloroketones and guanidine derivatives, and using deep eutectic solvents (DESs) as nonconventional, "green" and "innocent" reaction media, has been accomplished successfully. The combination of either glycerol or urea with choline chloride (ChCl) proved to be effective for decreasing the reaction time to about 4-6 h in contrast to the 10-12 h usually required for the same reaction run in toxic and volatile organic solvents and under an argon atmosphere. In addition, the use of the ChCl-urea as a DES also enables the direct isolation of triaryl-substituted 2-AI derivatives by means of a simple work-up procedure consisting in filtration and crystallization, and allows the recycle of the DES mixture.
View Article and Find Full Text PDFThe reaction of ortho-lithiated aryloxiranes with various enaminones straightforwardly affords new functionalized isochromanes as mixtures of two epimeric stereoisomers in reasonable to very good yields (50-90%). The two diastereomers, which show a high structural variability, can be easily separated by column chromatography.
View Article and Find Full Text PDFCycloreversion of α-lithiated phenyltetrahydrofuran was successfully tamed at -78 °C in a non-coordinating solvent in the presence of TMEDA. This anion showed excellent nucleophilicity and could be intercepted with a variety of structurally different electrophiles to give 2,2-disubstituted derivatives which can be further elaborated to γ-butyrolactones.
View Article and Find Full Text PDFThe first dynamic thermodynamic resolution of a racemic oxiranyllithium is described with selectivities of up to 82 : 18 from a selection of three types of chiral ligands (seven ligands in total). Both (-)-sparteine and its (+)-surrogate were surprisingly found to increase the enantiomerisation barrier.
View Article and Find Full Text PDFA valuable and direct method to access 2-substituted-2-phenyloxetanes by electrophilic quenching of the corresponding 2-lithiated derivative has, for the first time, been described. 2-Lithiated-2-phenyloxetane was found to be configurationally unstable. Evidence is presented to show that electron-transfer processes are also operative in the coupling reactions with electrophiles.
View Article and Find Full Text PDFThe employment of hexane/N,N,N',N'-tetramethylethylenediamine (TMEDA) dramatically hinders the racemization of those lithiated styrene oxides (trifluoromethyl-, chloro-, and phenylthio-substituted) that have been proven to be configurationally unstable in THF on the timescale of their reactions. The barriers to inversion and the activation parameters, calculated (Eyring equation) for reactions performed in THF, THF/TMEDA, and hexane/TMEDA, suggest the intervention of particular enantiomerization mechanisms for each case. The role of TMEDA in both coordinating and noncoordinating solvents has also been questioned and discussed in light of the kinetic data gathered and a model for deprotonation in hexane/TMEDA has also been proposed.
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