Acetophenone Derivatives Research Articles

Design of Iridium N-Heterocyclic Carbene Amino Acid Catalysts for Asymmetric Transfer Hydrogenation of Aryl Ketones

A series of chiral complexes of the form Ir(NHC)2(aa)(H)(X) (NHC = N-heterocyclic carbene, aa = chelated amino acid, X = halide) was synthesized by oxidative addition of α-amino acids to iridium(I) bis-NHC compounds and screened for asymmetric transfer hydrogenation of ketones. Following optimization of the reaction conditions, NHC, and amino acid ligands, high enantioselectivity was achieved when employing the Ir(IMe)2(l-Pro)(H)(I) catalyst (IMe = 1,3-dimethylimidazol-2-ylidene), which asymmetrically reduces a range of acetophenone derivatives in up to 95% enantiomeric excess.

Application of activated bentonite impregnated with PdO as green catalyst for acylation reaction of aromatic compounds

Friedel-Crafts acylation reaction is a well-known reaction to synthesize acetophenone derivatives, which have a broad spectrum of bioactivity. However, Friedel-Crafts acylation mostly used acetyl chloride as a reagent with Lewis acid as a homogeneous catalyst, which is a nonenvironmental friendly process. In this work, a simple and efficient Friedel-Crafts acylation reaction is reported using the activated bentonite impregnated with PdO (PdOAB) as the heterogeneous catalyst. The PdOAB catalyst material was prepared through a two-steps reaction, i.e., an acid activation of natural bentonite and impregnation of palladium(II) nitrate under alkaline conditions. The optimum condition of the acetophenone synthesis was evaluated using the catalyst material by varying the catalyst mass and reaction time. The acetophenone derivatives with R = -H, -Cl, -CH3, -OCH3, -OH, and -NH2 at the para position were successfully synthesized from its corresponding aromatic compounds with glacial acetic acid in 86.6%, 7.9%, 91.7%, 86.6%, 82.7%, and 78.9% yield, respectively. From the experimental results, we proposed that the catalysis mechanism was mainly facilitated by the acid sites of the PdOAB catalyst material. The PdOAB catalyst material did not significantly lose its catalytic activity after four-cycle processes. Therefore, a green method for acetophenone synthesis was established because the byproduct is water, and the catalyst material can be recovered.

Electrochemical reactivity of S-phenacyl-O-ethyl-xanthates in hydroalcoholic (MeOH/H2O 4:1) and anhydrous acetonitrile media

The electrochemical behavior of a series of S-phenacyl-O-ethyl-xanthates (O-ethyl-dithiocarbonate acetophenone derivatives) in hydroalcoholic (MeOH/H2O 4:1) and anhydrous media (ACN/TBAPF6) using carbon electrodes was studied. Cyclic voltammetry showed in hydroalcoholic media only two cathodic waves, whereas in ACN one anodic and two cathodic waves were present. The first cathodic wave corresponded to the reduction of the phenylketone group, whereas the first anodic was attributed to the xanthate unit. Macroelectrolysis on graphite and vitreous carbon at anodic and cathodic potentials, let us to explore the synthetic potential of this electrochemical reactions. With some compounds in hydroalcoholic media and using carbon electrodes, polymeric material was deposited on the electrode impeding the reaction; this deposit was characterized by AFM and SEM-EDS. The electroreduction on Ti electrode overcome this problem and gave the corresponding acetophenones (>95%). On the other hand, in ACN, small quantities of the dimeric 1,4-dicarbonyl compounds X-PhCOCH2CH2COPh-X (7–15%), as well as the corresponding acetophenones (ca. 50%) were isolated. Oxidation macroelectrolysis showed a very complicated transformation without synthetic value. The reaction mechanism for the reduction and the homolytic dissociation into the phenacyl radical was supported by DFT calculations.

Conformational Preference of 2'-Fluoro-Substituted Acetophenone Derivatives Revealed by Through-Space 1H-19F and 13C-19F Spin-Spin Couplings.

The conformational properties of 2′-fluoro-substituted acetophenone derivatives were elucidated based on Hα–F and Cα–F through-space spin–spin couplings (TS-couplings), which occur between two atoms constrained at a distance smaller than the sum of their van der Waals radii. This study revealed that 2′-fluoro-substituted acetophenone derivatives in solutions form exclusively s-trans conformers by analyzing their NMR spectra focused on the TS-couplings. The magnitudes of the coupling constants 5J (Hα, F) and 4J (Cα, F) correlate linearly with the value of the dielectric constant of the solvents. Furthermore, s-trans conformations of the two derivatives were confirmed by X-ray crystallographic analysis. These conformational preferences were consistent with the DFT calculations. The s-cis conformer, in which fluorine and oxygen atoms lie in a syn-periplanar mode, may be subject to strong repulsion between the two polar atoms and become unstable. The s-trans preference of the 2′-fluoro-substituted acetophenone derivatives may be utilized in drug design.

Hydroxy phenyl hydrazides and their role as corrosion impeding agent: A detail experimental and theoretical study

This study presents synthesis of environmentally benign corrosion inhibitors, hydroxy acetophenone derivative namely, N′-(1-(2-hydroxyphenyl) ethylidene) acetohydrazide (ATOH), N′-(1-(2-hydroxyphenyl) ethylidene) benzohydrazide (BZOH), 2-(1-(2-hydroxyphenyl) ethylidene) hydrazine-1-carbothioamide (TSCOH) and N′-(1-(2-hydroxyphenyl) ethylidene) hydrazinecarbothiohydrazide (TCBOH) and full investigation of their protecting ability against corrosion of MS in 1 M HCl medium. A variety of electrochemical experimental techniques viz., electrochemical impedance spectroscopy, and potentiodynamic polarization coupled with different microscopic techniques viz., scanning electron microscopy, atomic force microscopy, and x-ray photoelectron spectroscopy were run to evaluate the corrosion resistive behaviour of inhibitors. The surface feature of mild steel was further analysed by measuring contact angle in different electrolytic solutions. Furthermore, these wet-chemical experimental outcomes are well complemented from results analysed from ab initio DFT study and MD simulation. Furthermore, the MD simulation outcomes helped in visualization of interaction and thereby adsorption of inhibitors on Fe (110) surface.

Catalytic Asymmetric Homologation of Ketones with α-Alkyl α-Diazo Esters.

The homologation of ketones with diazo compounds is a useful strategy to synthesize one-carbon chain-extended acyclic ketones or ring-expanded cyclic ketones. However, the asymmetric homologation of acyclic ketones with α-diazo esters remains a challenge due to the lower reactivity and complicated selectivity. Herein, we report the enantioselective catalytic homologation of acetophenone and related derivatives with α-alkyl α-diazo esters utilizing a chiral scandium(III) N,N'-dioxide as the Lewis acid catalyst. This reaction supplies a highly chemo-, regio-, and enantioselective pathway for the synthesis of optically active β-keto esters with an all-carbon quaternary center through highly selective alkyl-group migration of the ketones. Moreover, the ring expansion of cyclic ketones was accomplished under slightly modified conditions, affording a series of enantioenriched cyclic β-keto esters. Density functional theory calculations have been carried out to elucidate the reaction pathway and possible working models that can explain the observed regio- and enantioselectivity.

A new synthetic approach for pyrazolo[1,5-a]pyrazine-4(5H)-one derivatives and their antiproliferative effects on lung adenocarcinoma cell line.

Starting from the 3,5-dimethyl pyrazole ring and acetophenone derivatives, five different N-propargylated C-3 substituted pyrazoles were obtained. These derivatives were reacted with different amine derivatives using Cs2CO3 in methanol and 11 different pyrazolo [1,5-a] pyrazine-4(5H)-one derivatives were obtained, which are not found in the literature. The cytotoxic effects of these derivatives in the A549 cell line were investigated. The 160µM concentration of two derivatives was found to increase cell death rate to 50%, and two derivatives increased cell death rate by up to 40%. The structure-activity relationship (SAR) study revealed an amide group with a long alkyl chain and benzene ring with a p-CF3 group could be important for efficiency. With theoretical ADMET studies of pyrazolopyrazine derivatives, pharmacokinetic phases were predicted to be suitable.

The intramolecular reaction of acetophenone N-tosylhydrazone and vinyl: Brønsted acid-promoted cationic cyclization toward polysubstituted indenes.

In the presence of TsNHNH2, a Brønsted acid-promoted intramolecular cyclization of o-(1-arylvinyl) acetophenone derivatives was developed, leading to polysubstituted indenes with complexity and diversity in moderate to excellent yields. In sharp contrast with either the radical or carbene involved cyclization of aldehydic N-tosylhydrazone with vinyl, a cationic cyclization pathway was involved, where N-tosylhydrazone served as an electrophile and alkylation reagent during this transformation.

An Approach in Synthesis of 1-Morpholino-2-phenylethane-1,2-dione Catalyzed by Copper (II) Bromide

A novel approach towards synthesis of α-Ketoamides was serendipitously found in acetophenone's reaction with a secondary amine catalyzed by copper (II) bromide. This methodology is a promising simple alternative to access biologically active compounds containing α-Ketoamides. Reactions were carried out at room temperature using dimethyl sulfoxide (DMSO) as solvent and catalyst loading at 10 mol %. The products were purified using a chromatographic method and analyzed extensively by spectroscopic methods, namely 1D (1H and 13C) and 2D NMR (HMBC and HSQC). The reaction of acetophenone and morpholine furnished a yield of 6%. Acetophenone derivatives bearing benzyl and acetyl groups were prepared from para-hydroxy acetophenone with 25% and 99% yields, respectively. The products were analyzed by spectroscopic method, namely 1H and 13C NMR. The presence of substituents, namely hydroxyl, benzyl, acetyl group, prevent the formation of α-Ketoamides. Formation of α-Ketoamides in this reaction condition was proposed as the result of the oxidation product in the catalytic cycle of Cu (II).

New lignans and acetophenone derivatives with α-glucosidase inhibitory activity from the leaves of Melicope patulinervia

Four new lignans, patulinones A−D (1–4) and three new acetophenone derivatives, patulinones E−G (5–7) were isolated from the leaves of Melicope patulinervia. Their structures were elucidated on the basis of the interpretation of HR-ESIMS, NMR, CD data. All the isolated compounds were evaluated for α-glucosidase inhibitory activity. Of the isolates, compound 4 was found to exhibit the strongest inhibition against α-glucosidase with IC50 value of 6.02 ± 0.46 μM.

Isolation, Characterization and Antiproliferative Activity of Secondary Metabolites from Tanacetum alyssifolium (Bornm.) Grierson

Secondary metabolites of Tanacetum alyssifolium (Bornm.) Grierson (Asteraceae) were investigated for the first time. Thirteen compounds including axillarin (1), Luteolin-7-O-β-glucoside (8) and rutin (13) as flavonoids, fraxetin (7), isofraxidin (9), isofraxidin-7-O-glucoside (11) and fraxidin (12) as coumarins, tatridin A (2), altissin (3), tamirin (4) and tanachin (5) as sesquiterpene lactones and 2,4-dihydroxy-6-methoxy acetophenone (6) and picein (10) as acetophenone derivatives were isolated from the methanol extract of the species. The structures of all isolated compounds were elucidated by 1D and 2D-NMR techniques and by comparing with the literature data. In addition, in vitro cytotoxic activity of all isolated compounds was evaluated against breast cancer MCF-7 cell line by XTT assay. Sesquiterpene lactones; tatridin A (2), tamirin (4) and tanachin (5) were found to be the most cytotoxic molecules against MCF-7 cell line.

1-(3-Tert-Butylphenyl)-2,2,2-Trifluoroethanone as a Potent Transition-State Analogue Slow-Binding Inhibitor of Human Acetylcholinesterase: Kinetic, MD and QM/MM Studies.

Kinetic studies and molecular modeling of human acetylcholinesterase (AChE) inhibition by a fluorinated acetophenone derivative, 1-(3-tert-butylphenyl)-2,2,2-trifluoroethanone (TFK), were performed. Fast reversible inhibition of AChE by TFK is of competitive type with Ki = 5.15 nM. However, steady state of inhibition is reached slowly. Kinetic analysis showed that TFK is a slow-binding inhibitor (SBI) of type B with Ki* = 0.53 nM. Reversible binding of TFK provides a long residence time, τ = 20 min, on AChE. After binding, TFK acylates the active serine, forming an hemiketal. Then, disruption of hemiketal (deacylation) is slow. AChE recovers full activity in approximately 40 min. Molecular docking and MD simulations depicted the different steps. It was shown that TFK binds first to the peripheral anionic site. Then, subsequent slow induced-fit step enlarged the gorge, allowing tight adjustment into the catalytic active site. Modeling of interactions between TFK and AChE active site by QM/MM showed that the “isomerization” step of enzyme-inhibitor complex leads to a complex similar to substrate tetrahedral intermediate, a so-called “transition state analog”, followed by a labile covalent intermediate. SBIs of AChE show prolonged pharmacological efficacy. Thus, this fluoroalkylketone intended for neuroimaging, could be of interest in palliative therapy of Alzheimer’s disease and protection of central AChE against organophosphorus compounds.

N-(Methyloxycarbonyl)thiophene sulfonamides as high affinity AT2 receptor ligands

A series of meta-substituted acetophenone derivatives, encompassing N-(alkyloxycarbonyl)thiophene sulfonamide fragments have been synthesized. Several selective AT2 receptor ligands were identified, among those a tert-butylimidazole derivative (20) with a Ki of 9.3 nM, that demonstrates a high stability in human liver microsomes (t½ = 62 min) and in human hepatocytes (t½ = 194 min). This methyloxycarbonylthiophene sulfonamide is a 20-fold more potent binder to the AT2 receptor and is considerably more stable in human liver microsomes, than a previously reported and broadly studied structurally related AT2R prototype antagonist 3 (C38). Ligand 20 acts as an AT2R agonist and caused an AT2R mediated concentration-dependent vasorelaxation of pre-contracted mouse aorta. Furthermore, in contrast to imidazole derivative C38, the tert-butylimidazole derivative 20 is a poor inhibitor of CYP3A4, CYP2D6 and CYP2C9. It is demonstrated herein that smaller alkyloxycarbonyl groups make the ligands in this series of AT2R selective compounds less prone to degradation and that a high AT2 receptor affinity can be retained after truncation of the alkyloxycarbonyl group. Binding modes of the most potent AT2R ligands were explored by docking calculations combined with molecular dynamics simulations.

Ring Opening of Donor–Acceptor Cyclopropanes with Acyclic 1,3-Diketones for the Synthesis of 1,6-Dicarbonyl Compounds

1,6-Dicarbonyl compounds, representing the formal addition products of the α-position of acetophenone derivatives to donor-acceptor cyclopropanes, were synthesized in two steps via first ring opening of donor-acceptor cyclopropanes with acyclic 1,3-diketones followed by DBU catalyzed retro-Claisen-type C-C bond cleavage reactions. In the first step, acyclic 1,3-diketones selectively worked as C-nucleophiles to add to donor-acceptor cyclopropanes. In the second step, the alkyl ketone part of the ring-opening products resulting from unsymmetrical 1,3-diketones was selectively cleaved in the presence of DBU in methanol.

Fluorescent properties of some polythiophenes synthesized from 2‐(thiophen‐3‐yl)acetohydrazide and acetophenone

AbstractIn this study, new polythiophenes containing hydrazone groups from derivatives of acetophenone were synthesized by chemical oxidative coupling polymerization. Ultraviolet‐visible spectroscopy (UV‐Vis) combined with infrared (IR) analyses proved the supposed structure of novel polythiophenes and proved conformance of the expected synthetic method. Morphology and surface properties of the synthesized polymers were investigated by field‐emission scanning electron microscopy (FE‐SEM). Thermal gravimetry analysis (TGA) has been reported that there was still the presence of small FeCl3 catalyst in polymers and polymers had a stable thermal stability under air atmosphere. The polymers displayed fluorescence emissions at about 590 nm attributed to the π‐conjugated polythiophene. Polymers without doping have a good electrical conductivity (around 4.03×10–7 S/cm at 1 MHz).

Ruthenium-Catalyzed α-Alkylation of Ketones Using Secondary Alcohols to β-Disubstituted Ketones.

An assortment of aromatic ketones was successfully functionalized with a variety of unactivated secondary alcohols that serve as alkylating agents, providing β-disubstituted ketone products in good to excellent yields. Remarkably, challenging substrates such as simple acetophenone derivatives are effectively alkylated under this ruthenium catalysis. The substituted cyclohexanol compounds displayed product-induced diastereoselectivity. Mechanistic studies indicate the involvement of the hydrogen-borrowing pathway in these alkylation reactions. Notably, this selective and catalytic C-C bond-forming reaction requires only a minimal load of catalyst and base and produces H2O as the only byproduct, making this protocol attractive and environmentally benign.

Catalysis for Fine Chemicals

2′-Methoxyacetophenone (2M) presents improved UVA absorption as compared with other acetophenone derivatives. On the basis of transient infrared spectroscopy it has been previously claimed that 2M is an interesting photosensitiser for cyclobutane pyrimidine dimers (CPDs) formation. In the present paper, a complete UV–Vis transient absorption spectroscopic characterisation of this compound is provided, including triplet-triplet spectra, triplet lifetimes and rate constants for quenching of 2M by a dimeric thymine derivative. Furthermore, generation of singlet oxygen has been proven by time-resolved near IR phosphorescence measurements. Overall, the obtained results confirm the potential of 2M as a DNA photosensitiser, not only for CPDs formation, but also for oxidative damage.

In vitro inhibitory effects of some acetophenone derivatives on some metabolic enzymes and molecular docking.

In this study, the acetophenone derivatives 1-6 were found to be effective inhibitor molecules for α-glycosidase, human carbonic anhydrases I and II (hCA I/II), and acetylcholinesterase (AChE), with Ki values in the range of 167.98 ± 25.06 to 304.36 ± 65.45 µM for α-glycosidase, 555.76 ± 56.07 to 1,043.66 ± 98.78 µM for hCA I, 598.63 ± 90.04 to 945.76 ± 74.50 µM for hCA II, and 71.34 ± 11.25 to 143.75 ± 31.27 µM for AChE, and IC50 values of 73.65-101.13 µM for tyrosinase. In the last step, molecular docking calculations were performed to compare the biological activities of molecules with their docking scores in these enzymes. The interactions of the studied molecules against human α-galactosidase (PDB ID: 1R47), hCA I (PDB ID: 3LXE), human AChE (PDB ID: 4M0E), hCA II (PDB ID: 5AML), and human tyrosinase (PDB ID: 5M8Q) were examined to compare the biological activity values. The ADME/T analysis (adsorption, distribution, metabolism, and discharge) was then performed for the future use of these molecules as drugs.

Next-Generation Paternò-Büchi Reagents for Lipid Analysis by Mass Spectrometry.

The Paternò-Büchi (PB) reaction is a photochemical reaction involving [2 + 2] cycloaddition between electronically excited carbonyl and carbon-carbon double bond (C═C). It has been established as a lipid derivatization strategy, leading to confident assignment of C═C locations in lipids when coupled with tandem mass spectrometry (MS/MS). Although acetone and several aryl-containing ketones or aldehydes have been explored as PB reagents, the chemical properties critical to achieving efficient conversion and minimum side reactions remain unclear. Herein, we investigated a set of acetophenone (AP) derivatives, aiming to provide insights into the development of new PB reagents with enhanced performance for lipid analysis. For AP derivatives, we found that electron-withdrawing groups (e.g., -F and -CF3) on the benzene ring improved the overall conversion, while a bulky group at the ortho-position decreased the conversion. Norrish Type I cleavage was largely diminished; however, the Norrish Type II side reaction was more competitive, producing products isomeric to the PB reaction products. Among all AP derivatives tested, 2',4',6'-trifluoroacetophenone (triFAP) showed the best performance. It offered a relatively high PB yield (20-30%) for different types of C═C, high sensitivity (sub-nM) for C═C identification, and accurate isomer quantitation. Due to the significantly reduced chemical interferences in shotgun analysis, triFAP provided better performance than that from acetone PB-MS/MS. An offline triFAP PB reaction was implemented in a liquid chromatography analysis workflow, which enabled the large-scale identification of phospholipids including C═C location isomers from a complex lipid extract.

Review on Darunaj-aqrabi (Doronicum hookeri C.B. Clarke): an Unexplored Medicinal Plant of Unani System of Medicine

Introduction: The rhizomes of medicinal plant Darunaj-aqrabi (Doronicum hookeri C.B. Clarke ex Hook.f.) (Family Asteraceae) has long been used in Unani system of medicine (USM) as Cardiac tonic (invigorative and exhilarant), nervine tonic, carminative, protective of the foetus, antidotary etc. in different dosage forms. It is included in specific drugs for heart and is much valuable for palpitation. Because of having antidotal characteristics and protective (corrective) attributes, the rhizomes are generally used in compound formulations having tonic effects for the body. Aim of the review: The study aims to reflect the importance of Darunaj-aqrabi in USM. This review provides essential data focusing on traditional use, phytochemistry, and pharmacological profile, thereby identifying research gaps and future opportunities for investigation and development of this plant. Materials and methods: All available information related to Darunaj-aqrabi in the internationally accepted scientific databases including Pub Med, Science Direct, Scopus, Sci Finder, Google Scholar, Microsoft academy and Web of Science were searched. Additional information was gathered from the classical text of USM on Herbs, Unani Pharmacopoeia, and so on. Results: The literature supported its use traditionally in formularies or by rural people as a digestive, carminative, protective of the foetus, cardiotonic, stomach tonic, liver tonic, lithotriptic, antidote etc. Its extract showed antibacterial, antifungal, hepatoprotective, and antioxidant activity. The main phytochemical constituents are alkaloids; saponins; flavonoids, photoactive thiophenes, sesquiterpene alcohol, paralianchol and its acetophenone derivatives. There is limited data available on this plant. Conclusion: The contemporary pharmacological studies showed the anti-microbial, antifungal, hepatoprotective, and antioxidant activity of Darunaj-aqrabi. However, most of the aspects of this herb have still not been identified. Along with this, there are inadequate details on the phytochemistry and toxicological profile. Due to the extensive traditional uses of Darunaj-aqrabi, more research on pharmacological activities, phytochemistry, toxicity and adverse effects tend to be required to determine its medicinal values.