Acetophenone Derivatives Research Articles

In silico Molecular Docking Study of Isatin and Acetophenone Derivatives as Antimicrobial Agent

The heterocyclic molecule isatin (1H-indole-2,3-dione) and its derivatives form a significant family of chemicals that can be employed as building blocks for the manufacture of pharmaceuticals. In the computational method known as docking, different software tools produce different positions at which ligands attach to their receptors. With the help of the Molegro virtual docker software (Version 6.0) and the PDB 3ACX, the present study attempts to perform a high-throughput in silico screening of 27 developed isatin and acetophenone-based derivatives. The docking results showed mol dock scores of -103.345 and one hydrogen bond interaction for the standard drug Ampicillin, on the other hand, the isatin and acetophenone-based derivatives YDA 27, YDA 26, YDA 25, YDA 17 and YDA 7 exhibited excellent mol dock scores and docking scores ranging from -104.23 to -121.126. Apart from the mol dock score, most of the studied compounds observed excellent hydrogen bonding with amino acids of PDB. Compound YDA 27, YDA 26, YDA 25, YDA 17 and YDA 7 showed 3 to 7 hydrogen bond interactions, however, the standard drug Ampicillin showed H-bond interaction with 1 amino acid Val 133 and Val 137. The results of the present study confirmed the significant antimicrobial potential of some designed isatin and acetophenone-based derivatives based on their mol dock values and other parameters when studied in silico, and the data obtained will give data that supports and provides perspectives in future research to develop an effective antimicrobial agent from these derivatives.

Design, synthesis, and anticancer evaluation of novel imidazo[1,2-c]thieno[3,2-e]pyrimidin derivatives

Derivatives of a novel heterocyclic system ethyl 2-(2-(aryl)-9-(aryl)imidazo [1,2-c]thieno [3,2-e]pyrimidin-3-yl)acetate have been obtained by successive reactions in four stages; Knoevenagel condensation between acetophenone derivatives with malononitrile to give 2-(1-arylethylidene)malononitrile, closing the thiophene ring in the latter to form 3-amino-2-5-arylthieno [2,3-d]pyrimidin-4-amines by using formamid, and one-pot three-component reaction of the 3-amino-2-5-arylthieno [2,3-d]pyrimidin-4-amine ring, Meldrum's acid, and various aryl glyoxal. The structure of the new compounds was confirmed based on elemental analysis and spectral data. The anticancer activity of some selected synthesized compounds was also examined. Although the compounds 10a-j are not considerable effective against the three cell lines tested, in comparison to etoposide, compound 10c is somewhat potential.

Chemoenzymatic Synthesis of Enantiopure Amino Alcohols from Simple Methyl Ketones

AbstractThis study highlights the straight‐forward synthesis of substituted 1,2‐amino alcohols from simple and readily available aromatic methyl ketones. Starting from acetophenone derivatives, the straight‐forward synthesis strategy involved an initial bromination of the alpha‐positioned methyl group in the first step, followed by a simple hydrolysis to the hydroxyketone (2‐hydroxyacetophenone). The hydroxylated intermediate was subsequently converted from Silicibacter pomeroyi to the final 1,2‐amino alcohol by using the transaminase. The transaminase‐catalyzed reaction proceeded with yields up to 62 % and always excellent enantiomeric excess of >99 %. Interestingly, the keto‐enol‐tautomerism of the hydroxyl ketone yields an unexpected amino alcohol isomer.

Synthesis of half-sandwich ruthenium(II) and iridium(III) complexes containing imidazole-based phosphinite ligands and their use in catalytic transfer hydrogenation of acetophenone with isopropanol

Two ionic liquids (3-(3‑chloro-2-hydroxypropyl)-1-vinyl-1H-imidazol-3-ium chloride and 3-(3‑chloro-2-hydroxypropyl)-1‑butyl‑1H-imidazol-3-ium chloride) were prepared from commercially available, inexpensive 1-vinyl imidazole or 1‑butyl imidazole, respectively, in ethanol at room temperature. Then, these ionic liquids were treated with PPh2Cl to obtain ionic liquid-based phosphinite ligands and the reaction of these phosphinites with [Ru(η6-benzene)(μ-Cl)Cl]2, [Ru(η6−p-cymene)(μ-Cl)Cl]2, or [Ir(η5-C5Me5)(μ-Cl)Cl]2 gave the corresponding ruthenium and iridium complexes. Structures of the synthesized compounds were clarified by multinuclear NMR and IR spectroscopy as well as microanalysis. Furthermore, the complexes were applied as catalysts in the transfer hydrogenation of acetophenone derivatives to afford the corresponding alcohols with high conversions. Notably, [Ru(Ph2POC8H11N2Cl2)(η6-benzene)Cl2] acts as a good catalyst, giving the corresponding alcohols in 97–98% yields in 15 min at 82 °C (TOF ≤ 400 h−1) for the transfer hydrogenation reaction in comparison to analogous complexes. The catalysts are also useful for a variety of related ketone substrates with various electronic and steric regulating groups.

Enantioselective C−P Bond Formation through C(sp3)−H Functionalization

AbstractAn enantioselective C−P bond formation has been developed through a C(sp3)−H activation in an oxidation step followed by an organocatalyzed hydrophosphonylation protocol. The asymmetric organocatalytic Pudovik reaction has been achieved following a one‐pot strategy, starting from different benzylic and allylic alcohols and dibenzyl phosphite, using MnO2 as the oxidant and a chiral squaramide as organocatalyst. The scope of the reaction provides enantiomerically enriched α‐hydroxy phosphonates with yields from 40% to >95% and enantioselectivities from 64% to >99%. Furthermore, the use of this methodology has been demonstrated to form a tetrasubstituted carbon stereocenter, generating an acetophenone derivative in situ, using diphenyl phosphite. Therefore, this approach represents an asymmetric strategy for constructing chiral C−P bonds, which are of interest to the pharmaceutical industry.

Monobromination of 2-hydroxy-6-methoxyacetophenone and studies of the non-covalent interactions in the crystal structure of 3-bromo-2-hydroxy-6-methoxyacetophenone

In principle both position C-3 and C-5 of 2-hydroxy-6-methoxyacetophenone (1) should be able to react with N-bromosuccinimide (NBS), being jointly activated by the meta directing effect of the carbonyl group and strongly so by the ortho-para directing resonance effects of the hydroxyl and methoxy group, respectively. However, this acetophenone derivative reacted with NBS in acetic acid to afford 3-bromo-2-hydroxy-6-methoxyacetophenone (2), exclusively. Intramolecular hydrogen (CO…HO) bonding interaction in ortho-hydroxycarbonyl compounds result in a thermodynamically stable six-membered ring with the resultant complex resembling naphthalene. C-3 becomes the α-position of this naphthaneloid scaffold and therefore the most activated/nucleophilic for electrophilic attack by NBS. The molecular electrostatic potential (MEP) map of substrate 1 shows that C-3 accommodates higher negative charge than that on C-5 making the former centre more susceptible to electrophilic attack. Moreover, density functional theory (DFT) method also predicted the 3-Br isomer to be more stable and favoured than the 5-Br form in acetic acid solution and also in the gas phase. Single crystals of the monobrominated acetophenone 2 were obtained and the structure of this compound was accurately established with the aid of X-ray diffraction technique complemented with spectroscopic (NMR, FT-IR, Uv-Vis and HR-MS) and DFT methods. The intermolecular interaction pattern was studied by Hirshfeld surface analysis along with 2D fingerprint diagrams. The DFT calculations were also performed in the gas phase to correlate the experimental results with the simulated data.

Observation of the two-photon transition enhanced first hyperpolarizability spectra in cinnamaldehyde derivatives: A femtosecond regime study.

The application of nonlinear optical effects in optoelectronic devices is still scarce because the irradiance threshold necessary to induce a specific effect is very high. In this context, knowing the frequency-resolved first order molecular hyperpolarizability (β) is essential to identifying regions where this response is intense enough to allow for applications in commercial devices. Thus, herein, we have determined the β spectral dependence of five new push-pull cinnamylidene acetophenone derivatives using femtosecond laser-induced Hyper-Rayleigh Scattering (HRS). A considerable increase in β values was observed in molecules. We found remarkable β values in regions near the two-photon resonance, which are mediated by electron withdrawing and donating groups. This effect was mapped using wavelength-tunable femtosecond Z-scan technique. Furthermore, it was modeled in light of the sum-over-states approach for the second- and third-order nonlinearities. Finally, our outcomes suggest a strategy to obtain large β values mediated by the 2PA transition.

One-pot synthesis of novel poly-substituted 3-cyanopyridines: Molecular docking, antimicrobial, cytotoxicity, and DFT/TD-DFT studies

Novel pyridine-3-carbonitrile derivatives, denoted as (4a-j), were synthesized using a convergent synthetic approach that involved a one-pot four-component reaction. This was achieved by utilizing a combination of various aromatic aldehydes, acetophenone derivatives, malononitrile, and four different sodium alkoxide solutions. The synthesized compounds were characterized using various spectroscopic techniques such as IR, 1HNMR , 13CNMR , and elemental analysis. Molecular docking simulations were employed to investigate the binding affinity of compounds (4a-j) towards two proteins, DHFR and HT-hTS. The results revealed that 4-(4-chlorophenyl)-2-ethoxy-6-phenyl-pyridine-3-carbonitrile (4a) compound exhibited the highest binding affinity score (ΔG = -8.06 Kcal/mol) upon docking into the active site of DHFR, while 2-(4-nitrophenyl)-6-(4-chlorophenyl)-4-ethoxy-pyridine-3-carbonitrile (4d) compound displayed the strongest binding affinity score (ΔG = -4.17 Kcal/mol) when docked to the active site of HT-hTS. These results were supported by the cytotoxic activity of selected compounds (4a, 4b, 4e, and 4 h) against human cancer cell lines (MCF7, HT29, and A2780) as well as normal human fetal lung fibroblast (MRC5) using MTT assay. The cytotoxicity analyses revealed that compound (4a) displayed cytotoxic activity against all cancer cell lines, particularly human colorectal carcinoma (HT29) with an IC50 value of 2.243±0.217 μM, which is lower than that of the reference drug (Doxorubicin) with an IC50 value of 3.964±0.360 μM. Furthermore, compound (4a) exhibited a lower cytotoxic effect on normal human fetal lung fibroblast (MRC5) with an IC50 value of 2.222±0.137 μM, as compared to the IC50 value of the reference drug (Doxorubicin) which was 2.476±0.033 μM. The antimicrobial activity of selected compounds such as (4a, 4c, and 4f) was also evaluated against a panel of microorganisms, including two gram-positive strains (Staphylococcus aureus and Enterococcus faecalis) and two gram-negative strains (Escherichia coli and Pseudomonas aeruginosa). The zone of inhibition and minimum inhibition concentration (MIC) demonstrated the potency of these compounds. Specifically, compounds 4-(4-chlorophenyl)-2-ethoxy-6-phenyl-pyridine-3-carbonitrile (4a) and 4-(4-methoxyphenyl)-2‑methoxy-6-(4-nitrophenyl)-pyridine-3-carbonitrile (4f) exhibited MIC of 0.013 µM against E. coli strains, which is comparable to that of the reference drug amoxicillin (MIC=0.01 µM). Finally, Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) studies were performed on compounds (4a-j) to obtain a more comprehensive understanding of the structure-activity relationship and solvatochromic behavior of these molecules. Overall, the results suggest that compound (4a) could potentially serve as a promising cytotoxic and antibacterial agent with a better safety profile and reduced side effects on normal cells.

Application of Nanomagnetic Metal-Organic Frameworks in the Green Synthesis of Nicotinonitriles via Cooperative Vinylogous Anomeric-Based Oxidation.

In the current study, we synthesized a new nanomagnetic metal-organic framework Fe3O4@MIL-53(Al)-N(CH2PO3)2 and characterized it using various techniques. This nanomagnetic metal-organic framework was used for the synthesis of a wide range of nicotinonitrile derivatives as suitable drug candidates by a four-component reaction of 3-oxo-3-phenylpropanenitrile or 3-(4-chlorophenyl)-3-oxopropanenitrile, ammonium acetate (NH4OAc), acetophenone derivatives, and various aldehydes including those bearing electron-donating, electron-withdrawing, and halogen groups, which afforded desired products (27 samples) via a cooperative vinylogous anomeric-based oxidation (CVABO) mechanism under solvent-free conditions in excellent yields (68-90%) and short reaction times (40-60 min). Increasing the surface-to-volume ratio, easy separation of the catalyst using an external magnet, and high chemical and temperature stability are the advantages of the described nanomagnetic metal-organic frameworks.

Syntheses of novel disperse dyes based on arylazophenols: Synthesis, characterizations and applications

ABSTRACT. Three compounds, phenyl propenone, p-tolyl propenone, and bromo phenylpropenone derivatives 3a-c were produced in good yields via condensation derivatives of acetophenone with dimethyl formamide dimethyl acetal (DMFDMA) in presence of xylene as a solvent. Compounds 5a-f were produced by coupling the enaminones 3a-c with diazonium chloride 4a or 4b. Compounds 5a-f were reacted with acetone to create novel disperse dyes 9a-f. Mass spectra, (FT-IR), elemental analysis, and 1H-NMR spectra were used to confirm the chemical structure of the new dyes. The new disperse dyes were used in dyeing polyester fabrics at low temperature, and fabrics with colors ranging from yellowish brown to dark yellowish brown were obtained. Thus, the different fastness properties of these dyed fabrics were studied, which gave excellent results. Finally, the biological activity of these new dyes was studied, which showed that they have biological activity against bacteria and fungi.
 
 KEY WORDS: Azo dye, Carrier, Low temperature dyeing, Arylazophenols, Color fastness
 Bull. Chem. Soc. Ethiop. 2023, 37(4), 993-1002. 
 DOI: https://dx.doi.org/10.4314/bcse.v37i4.15

Computationally Supported Inversion of Ketoreductase Stereoselectivity.

Whereas directed evolution and rational design by structural inspection are established tools for enzyme redesign, computational methods are less mature but have the potential to predict small sets of mutants with desired properties without laboratory screening of large libraries. We have explored the use of computational enzyme redesign to change the enantioselectivity of a highly thermostable alcohol dehydrogenase from Thermus thermophilus in the asymmetric reduction of ketones. The enzyme reduces acetophenone to (S)-1-phenylethanol. To invert the enantioselectivity, we used an adapted CASCO workflow which included Rosetta for enzyme design and molecular dynamics simulations for ranking. To correct for unrealistic binding modes, we used Boltzmann weighing of binding energies computed by a linear interaction energy approach. This computationally cheap method predicted four variants with inverted enantioselectivity, each with 6-8 mutations around the substrate-binding site, causing only modest reduction (2- to 7-fold) of kcat /KM values. Laboratory testing showed that three variants indeed had inverted enantioselectivity, producing (R)-alcohols with up to 99 % enantiomeric excess. The broad substrate range allowed reduction of acetophenone derivatives with full conversion to highly enantioenriched alcohols. The results demonstrate the use of computational methods to control ketoreductase stereoselectivity in asymmetric transformations with minimal experimental screening.

Green Synthesis of Novel Pyridines via One-Pot Multicomponent Reaction and Their Anti-Inflammatory Evaluation.

A functional and environmentally green procedure for the design of novel pyridine 5a-h and 7a-d derivatives through two pathways is presented. The first pathway is via a one-pot, four-component reaction of p-formylphenyl-4-toluenesulfonate (1), ethyl cyanoacetate (2), acetophenone derivatives 3a-h or acetyl derivatives 6a-d, and ammonium acetate (4) under microwave irradiation in ethanol. The advantages of this method are an excellent yield (82%-94%), pure products, a short reaction time (2-7 min), and low-cost processing. The second pathway was obtained by the traditional method with treatment of the same mixture under refluxing in ethanol, which afforded the same products, 5a-h and 7a-d, in less yield (71%-88%) and over a longer reaction time (6-9 h). The constructions of the novel compounds were articulated via spectral and elemental analysis. Overall, the compounds have been designed, synthesized, and studied for their in vitro anti-inflammatory activity using diclofenac as a reference drug (5 mg/kg). The most potent four compounds, 5a, 5f, 5g, and 5h, showed promising anti-inflammatory activity.

Biological determination, molecular docking and Hirshfeld surface analysis of rhoduim(I)-N-heterocyclic carbene complex: Synthesis, crystal structure, DFT calculations, optical and non linear optical properties

The synthesis and characterization of 1-(isobutyl)-3-(2.3.5.6 tetramethylbenzyl)-5.6-dimethylbenzimidazolium chloride and its N-functionalized Rhodium(I) N-heterocyclic carbene complex have been described. The ligand 2 and the complex 3 were characterized by IR, 1H NMR and 13C NMR spectroscopy, DART-TOF mass spectrometry and elemental analysis. The coordination mode of the complex was confirmed by single crystal XRD analysis. We performed a comparative theoretical study in order to investigate the impact of the iridium on the optoelectronic and non-linear optical properties of the complex. The M06-2X functional with the mixed basis set (6-31G(d): def2tzvp) was found the best method for optimizing the studied complex since it displayed close geometric data to the experiment. As a novelty in this work, iridium was found to be a performer for NLO applications over rhodium. This Rh(I)- N-Heterocyclic carbenes (NHC) showed good catalytic performance for the hydrosilylation of acetophenone derivatives with triethylsilane at 80 °C for 1 h by using 1 mol % of this complex. The cytotoxic properties of the rhodium(I)–NHC complex have been assessed against MCF7 and MDA-MB-231 cancer cells and the complex show interest activity. The in vitro antibacterial activity of this complex were also investigated against Micrococcus luteus LB 14110, Listeria monocytogenes ATCC 19117, Salmonella Typhimurium ATCC 14028, Staphylococcus aureus ATCC 6538, Pseudomonas aeruginosa and Candida albicans microorganisms indicated their significant biological potential. Additionally, the antioxidant activity of the same complex has been analyzed with DPPH∙ free radical through spectrophotometric method and the result inferred them as an antioxidant. The potential biological activities were investigated by using molecular docking analysis.

Synthesis and Structural Characterization of some 3-oxapentane Podand Derivatives

A series of eight 3-oxapentane podand derivatives was successfully prepared based on the croton condensation reaction from 1,5-bis(aryl)-1,5-dithia-3-dioxadecane and 1,5-bis(aryl)-1,3,5-trioxadecane with bezaldehyde or acetophenone derivatives in acidic condition. These synthesized derivatives have structure of acyclic crown rings inserted by polyether or polythiaether chain and vinyl ketone chain conjugated with aryl group. Therefore, they are important sources for host-guest chemistry. They can wrap around a central alkali metal cations as well as organic cations and anions or even molecules to make interesting ion pair receptors. Structure of new podands was determined by spectral analyses including IR, 1H NMR, MS spectrocopies.

Traveling across Life Sciences with Acetophenone-A Simple Ketone That Has Special Multipurpose Missions.

Each metabolite, regardless of its molecular simplicity or complexity, has a mission or function in the organism biosynthesizing it. In this review, the biological, allelochemical, and chemical properties of acetophenone, as a metabolite involved in multiple interactions with various (mi-cro)organisms, are discussed. Further, the details of its biogenesis and chemical synthesis are provided, and the possibility of its application in different areas of life sciences, i.e., the status quo of acetophenone and its simple substituted analogs, is examined. In particular, natural and synthetic simple acetophenone derivatives are analyzed as promising agrochemicals and useful scaffolds for drug research and development.

Synthesis and Some Transformations of New Acetophenone Derivatives Containing a Carbamate Moiety

Synthesis and Some Transformations of New Acetophenone Derivatives Containing a Carbamate Moiety

Synthesis of microwave-assisted carboxamides in Triton WR-1339-induced hyperlipidemic rats: possible hypolipidemic heterocyclic compounds.

The hypolipidemic effect of furan carboxamide derivatives was investigated using the Triton WR-1339 rat model. Nineteen compounds were synthesized, including furan-2-carboxamides of benzophenones and acetophenones (a(1-4)), anilines and amine derivatives (a(5-9)), picolinic-2-carboxamide derivatives of benzophenones and acetophenone (a(10-12)) and furan-2-carboxylate esters of benzophenones and acetophenones, substituted phenols and alcohols (b(1-7)). All the necessary steps were taken to synthesize, purify, and characterize these compounds. They were synthesized by reacting acyl chlorides of the heterocycles with their corresponding amines in the presence of pyridine and tert-butyl acetate. While the conventional heating method yielded acceptable yields for some of the reactions under reflux, the microwave synthesis reactor achieved significantly higher yields for others. Rats with hyperlipidemia were induced with Triton WR-1339 and then subjected to in vivo testing via an intraperitoneal injection of 200 mg kg-1 Triton WR-1339. The model was tested using an oral dose of bezafibrate (100 mg kg-1). After 7 hours of treatment with Triton, the new derivatives represented by compounds a(1-2), a(4-5), a7, and a(10-12) showed significant activity against the complete lipid profile, including a decrease in triglyceride, total cholesterol, and low-density lipoprotein cholesterol and an increase in high-density lipoprotein cholesterol plasma levels. At 20 mg kg-1 dose, these compounds were superior to other lipid-lowering agents in reducing triglyceride levels and slightly increased high-density lipoprotein cholesterol levels. These results indicate a mutual mechanism of action of novel compounds with fibrates, where they have a marked effect on triglyceride and high-density lipoprotein cholesterol levels; for example, a5 causes a significant reduction (p 0.0001) of triglyceride levels by 86%, and a remarkable increase (p 0.0001) in high-density lipoprotein cholesterol plasma levels by 65% as compared to hyperlipidemic rats.

Cobalt-Catalyzed Oxyalkylation Reaction of Styrenes: Rapid Access to α-Alkyl Substituted Acetophenone Derivatives

Cobalt-Catalyzed Oxyalkylation Reaction of Styrenes: Rapid Access to α-Alkyl Substituted Acetophenone Derivatives

One-pot synthesis of 2,4,6-triarylpyridines by cyclocondensation between aryl aldehyde, acetophenone derivative, and ammonium acetate using Al/Ag3PO4 as a new and green bimetallic catalyst

One-pot synthesis of 2,4,6-triarylpyridines by cyclocondensation between aryl aldehyde, acetophenone derivative, and ammonium acetate using Al/Ag3PO4 as a new and green bimetallic catalyst

Rational Design of a Facially Coordinating P,N,N Ligand for Manganese-Catalysed Enantioselective Hydrogenation of Cyclic Ketones.

DFT calculations on the full catalytic cycle for manganese catalysed enantioselective hydrogenation of a selection of ketones have been carried out at the PBE0-D3PCM //RI-BP86PCM level. Mn complexes of an enantiomerically pure chiral P,N,N ligand have been found to be most reactive when adopting a facial coordination mode. The use of a new ligand with an ortho-substituted dimethylamino-pyridine motif has been calculated to completely transform the levels of enantioselectivity possible for the hydrogenation of cyclic ketones relative to the first-generation Mn catalysts. In silico evaluation of substrates has been used to identify those likely to be reduced with high enantiomer ratios (er), and others that would exhibit less selectivity; good agreements were then found in experiments. Various cyclic ketones and some acetophenone derivatives were hydrogenated with er's up to 99 : 1.