The Menshutkin reaction represents the alkylation of tertiary amines by alkyl halide where the reactants are neutral and the products, quaternary ammonium salts, are two ions with opposite signs. The ...most commonly used organic solvents in quaternization reactions are volatile organic solvents (VOSs), namely acetone, anhydrous benzene, dry dichloromethane (DCM), dimethylformamide (DMF) and acetonitrile (ACN). The purpose of this work was to examine eutectic solvents as a “greener” alternative to conventional solvents so that quaternization reactions take place in accordance with the principles of green chemistry. Herein, sixteen eutectic solvents were used as replacements for volatile organic ones in quaternization reactions of isonicotinamide with substituted phenacyl bromides. The reactions were carried out at 80 °C by three synthetic approaches: conventional (4–6 h), microwave (20 min) and ultrasound (3 h). Microwave-assisted organic reactions produced the highest yields, where in several reactions, the yield was almost quantitative. The most suitable eutectic solvents were based on choline chloride (ChCl) as the hydrogen bond acceptor (HBA) and glycerol, oxalic or levulinic acid as hydrogen bond donors (HBDs). The benefits of these three deep eutectic solvents (DESs) as a medium for quaternization reactions are the simplicity of their preparation for large-scale production, with inexpensive, available and nontoxic starting materials, as well as their biodegradability.
Seven pyridoxal dioxime quaternary salts (1–7) were synthesized with the aim of studying their interactions with human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The synthesis was ...achieved by the quaternization of pyridoxal monooxime with substituted 2-bromoacetophenone oximes (phenacyl bromide oximes). All compounds, prepared in good yields (43–76%) and characterized by 1D and 2D NMR spectroscopy, were evaluated as reversible inhibitors of cholinesterase and/or reactivators of enzymes inhibited by toxic organophosphorus compounds. Their potency was compared with that of their monooxime analogues and medically approved oxime HI-6. The obtained pyridoxal dioximes were relatively weak inhibitors for both enzymes (Ki = 100–400 µM). The second oxime group in the structure did not improve the binding compared to the monooxime analogues. The same was observed for reactivation of VX-, tabun-, and paraoxon-inhibited AChE and BChE, where no significant efficiency burst was noted. In silico analysis and molecular docking studies connected the kinetic data to the structural features of the tested compound, showing that the low binding affinity and reactivation efficacy may be a consequence of a bulk structure hindering important reactive groups. The tested dioximes were non-toxic to human neuroblastoma cells (SH-SY5Y) and human embryonal kidney cells (HEK293).
We evaluated the potential of nine vitamin B3 scaffold-based derivatives as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors, as a starting point for the development of novel ...drugs for treating disorders with cholinergic neurotransmission-linked pathology. As the results indicate, all compounds reversibly inhibited both enzymes in the micromolar range pointing to the preference of AChE over BChE for binding the tested derivatives. Molecular docking studies revealed the importance of interactions with AChE active site residues Tyr337 and Tyr124, which dictated most of the observed differences. The most potent inhibitor of both enzymes with
of 4 μM for AChE and 8 μM for BChE was the nicotinamide derivative 1-(4'-phenylphenacyl)-3-carbamoylpyridinium bromide. Such a result places it within the range of several currently studied novel cholinesterase inhibitors. Cytotoxicity profiling did not classify this compound as highly toxic, but the induced effects on cells should not be neglected in any future detailed studies and when considering this scaffold for drug development.
The synthesis of 14 hydrazone compounds derived from pyridoxal, pyridine-4-carbaldehyde, and quinoline-2-carbaldehyde using two methods, conventional method in deep eutectic solvents (DESs) and ...effective combination of ultrasound and DESs, is presented in this paper. In addition, the possibility of using 12 choline chloride (ChCl)-based DESs as an alternative to organic solvents was investigated. The results show that the application of ultrasound not only improves the reaction yield but also shortens the reaction time. The prepared compounds synthesized at room temperature were analyzed via NMR spectroscopy and MS spectrometry. The studies confirmed that the DESs ChCl:malonic, oxalic, levulinic, and trans-cinnamic acid can be excellent alternatives to classical organic solvents. By the combined use of DESs and the ultrasonic method, compound 11 was obtained in a nearly quantitative yield of 98% in DES ChCl:oxalic acid. The advantages of using DESs as reaction media are that they are biodegradable, nontoxic, recyclable, and can be easily prepared with inexpensive starting materials. The results of recycling DESs show that they can be used up to the fourth recycling cycle without significantly changing the reaction yield.
The quaternization reactions of nicotinamide, with different electrophiles: methyl iodide and substituted 2-bromoacetophenones (4-Cl, 4-Br, 4-H, 4-CH₃, 4-F, 4-OCH₃, 4-Ph, 2-OCH₃, 4-NO₂) are reported. ...The preparations were carried out by conventional synthesis and under microwave irradiation in absolute ethanol and acetone. The synthesis performed by microwave dielectric heating significantly improved yield, up to 8 times, and shortened down the reaction time from
one day in conventional, to 10⁻20 min. The structures of the synthesized compounds were confirmed by IR, ¹H- and
C-NMR spectroscopy, mass spectrometry and elemental analysis. The compounds have been screened for antifungal activities against
,
,
and
at concentrations of 10 µg/mL and 100 µg/mL. Six compounds showed the strong inhibition of mycelium growth at a concentration of 10 µg/mL. All tested compounds revealed the great inhibitory activities against
at a concentration of 100 µg/mL.
Organske reakcije u vodi Dajana Gašo-Sokač; Valentina Bušić; Dora Zobundžija ...
Kemija u industriji; časopis kemičara i tehnologa Jugoslavije,
09/2023, Letnik:
72, Številka:
9-10
Journal Article
Recenzirano
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Velik je izazov provoditi organske reakcije u vodi. U posljednjem desetljeću broj znanstvenih istraživanja koja se bave proučavanjem vode kao zelenog otapala nastavio je eksponencijalno rasti. Osim ...što je jeftina, voda nije štetna za okoliš, a ponekad daje potpuno neočekivanu reaktivnost u kemijskim reakcijama. Postoji širok raspon organskih reakcija koje se mogu odvijati u vodi: od uobičajenih oksidoredukcijskih reakcija, reakcija koje uključuju karbokatione, pericikličkih reakcija, reakcija prijelaznih metala itd. Organske reakcije u vodenom mediju primjenjuju se u kemiji ugljikohidrata i kemijskoj modifikaciji biomolekula. U novije vrijeme voda se upotrebljava kao medij u mikrovalnoj sintezi. Ovaj pregledni rad daje uvid u važnost ovog područja budući da se organske reakcije u vodi kao otapalu odvijaju po principima zelene kemije.
Global food waste has a huge impact on the environment, as it is a source of greenhouse gas emissions and wasted natural resources. Across the world, over 30% of food is lost or wasted each year. ...Aside from this, the food industry, as well, is one of the biggest sources of agro-industrial waste and by-products, which can be valorized and used for different purposes. Such waste is a good source of bioactive organic compounds that can be extracted without altering their properties, where deep eutectic solvents can serve as green solvents and as an excellent replacement for volatile organic solvents. Isolated compounds can be used in innovative food production, chemical production, cosmetics and other industries. Deep eutectic solvents have attracted extraordinary attention due to their advantages such as environmental friendliness, availability and easy preparation, easy handling and utilization of non-toxic components for their formation. Due to these properties, they are a greener alternative to classic organic solvents for many processes, including extractions. In this paper, we review the utilization of deep eutectic solvents as potential green media for the extraction of organic compounds such as polyphenols, carbohydrates, proteins and alkaloids from by-products of the food industry and from agro-industrial waste.
Most organic solvents used in quaternization reactions are volatile, hazardous, toxic and form by-products, thus inducing health issues and pollution. Deep eutectic solvents are greener alternatives, ...but they have not been tested yet in the quaternization reaction. Here we propose eutectic solvents in the quaternization reaction of nicotinamide with substituted 2-bromoacetophenones. The reaction was performed at 80 °C by three synthetic approaches: conventional during 2–6 h, microwave during 20 min and ultrasonic during 3 h. The highest yields of about 98% were obtained by microwave. The most suitable eutectic solvents were choline chloride with either urea, oxalic or levulinic acid. The use of deep eutectic solvents has several advantages: environmental benignity, biodegradability, easy purification and simple preparation. All tested compounds showed antifungal activities against
Botrytis cinerea
,
Colletotrichum acutatum
,
Alternaria radicina
and
Fusarium graminearum
at 10 and 100 µg/mL.
Synthesis, thermal and spectroscopic (FTIR and NMR) studies, DFT molecular modelling, and antiproliferative activity against four cancer cell strands of the four new palladium(II) complexes with ...N-benzyliminodiacetic acid and its para-substituted (Cl, NO2, and MeO) derivatives.
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•New Pd(II) complexes with N-benzyliminodiacetic acid and p-substituted derivatives.•Spectroscopical (FTIR, NMR) and thermogravimetric characterization.•Molecular geometry and IR spectra modelled using DFT calculation.•Antiproliferative activity tested on four cancer cell strands.
The reactions of N-benzyliminodiacetic acid (BnidaH2) and its para-substituted derivatives, namely: N-(p-chlorobenzyl)iminodiacetic acid (p-ClBnidaH2), N-(p-nitrobenzyl)iminodiacetic acid (p-NO2BnidaH2) and N-(p-methoxybenzyl)iminodiacetic acid (p-MeOBnidaH2) with paladium(II) chloride and 2,2′-bipyridine, were performed in water-acetonitrile solutions. Four new prepared complexes Pd(Bnida)(bipy)∙2H2O (1), Pd(p-ClBnida)(bipy)∙4H2O (2), Pd(p-NO2Bnida)(bipy)∙2H2O (3) and Pd(p-MeOBnida)(bipy)∙3H2O (4) were identified by means of chemical analysis and mass spectrometry, and characterized by infrared spectroscopy and thermal analysis (TG/DTA). The molecular geometry and infrared spectra of these four complexes were modelled using DFT calculations at the BP86/def2-TZVP (Pd: ECP) level of theory. Extensive NMR studies have shown the presence of two isomers in solution (DMSO). The characterized palladium(II) complexes demonstrate valuable antiproliferative activity against Caco-2, SW620, NCI-H358 and MDCK I reducing cell growth from 71.7% to 79.9% (10−4 M) (1; 4). PANC-1 display mild sensitivity and slow reduction in cell growth (less than 50%) while BJ present higher viability range and proliferative status. BJ proliferation after exposure to palladium complexes at 10−4 M concentration ranged from 55.2% to 83.5% (1–4). In descending order, antiproliferative effect of tested palladium complexes is, as follows: 4 > 1 > 2 > 3.
Quaternary salts of pyridoxal oxime have been synthesized by the quaternization of pyridoxal oxime with substituted phenacyl bromides using microwave heating. Microwave-assisted rapid synthesis was ...done both in solvent (acetone) and under solvent-free conditions. Good to excellent yields (58%-94%) were obtained in acetone in very short reaction times (3-5 min) as well as in the solvent-free procedure (42%-78%) in very short reaction times (7-10 min) too. Effective metodologies for the preparation of pyridoxal oxime quaternary salts, having the advantagies of being eco-friendly, easy to handle, and performed in shorter reactions time are presented. The structure of compound 7, in which a 4-fluorophenacyl moiety is bonded to the pyridinium ring nitrogen atom, was unequivocally confirmed by the single-crystal X-ray diffraction method.
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