Ketones 1a Research Articles

Design, Synthesis and Antibacterial Assessment of Active (4-Arylazo-3-Methyl-2-Thienyl) 4-Antipyrine Ketones.

The chemicals formed from antipyrines are flexible organic building blocks that are employed in the development of pharmaceuticals. By diazotizing (4-arylazo-3-hydroxy-2-thienyl) 4-antipyrine ketones 1a, 1b and 1c and (4-arylazo-3-methyl-2-thienyl) 4-antipyrine ketones (2a, 2b and 2c) further replaced with six other coupling components, a broad spectrum of hybrid molecules have been created. Mass spectra, NMR, FTIR, and elemental analyses have all been used to confirm the structures of the synthesised compounds. The antimicrobial screening was investigated by agar well diffusion and diluting the broth technique against both Gram-negative and positive-tested bacterial strains. (3-methyl-5-(phenylamino)-4-(4-tolylazo)-2-thienyl) 4-antipyrine ketone (2a) was found to be superior to Ciprofloxacin against test strains: Acinetobacter sp (34.33±1.15 mm), Listeria monocytogenes (29.33±1.15 mm) and Streptococcus sp. (19.33±1.15 mm). Also, good to moderate activities were expressed as minimum inhibitory concentration (MIC) and minimum bacterial concentration (MBC) which were recorded at 9±1 to 59.67±4.51 μg/mL and 16±4 to >512 μg/mL, respectively, using compounds 2a, 2b, and 2c. MBC/MIC ratio showed, that only, 2a and 2b have a bactericidal effect but other antipyrines with bacteriostatic strength. To conclude, it was suggested that the use of these novel synthesized (4-arylazo-3-methyl-2-thienyl) 4-antipyrine ketone derivatives molecules as a new chemical class of antimicrobial agents to perform new drug discovery in pharmaceutical preparations and medicinal research.

Synthesis, Characterization, and Optimization of Novel Furan-ring Fused Chalcones via Radical Cyclization of α,β-Unsaturated Ketones and Cyclic Ketone

Abstract: Novel Furan-ring Fused Chalcones (FFC) were synthesized using a radical cyclization reaction of α,β-unsaturated ketones with cyclic ketone as the model reaction to attain this goal. In this study, traditional and microwave-assisted methods for the efficient and cost-effective synthesis of furan-ring fused chalcones in mild reaction conditions are compared and optimized. The goal is to develop a reliable and adaptable synthetic technique that may be used to produce these useful chalcone derivatives quickly and effectively. The optimal experimental conditions for these reactions were carefully determined using two independent methodologies: conventional (Method A) and microwave (Method B). The results indicated that the proposed method B could be used effectively in the future to synthesize novel furans with short reaction times and acceptable yields (87-94 %), and products were purified by column chromatography and preparative thin layer chromatography (PTLC). All new compounds were characterized by 1H-NMR, 13C-NMR, LC-MS, and elemental analyses.

Fluorescent 2-carbonyl carbazole ketones: Photophysical properties, molecular structure and selective detection of Fe3+ ion

Owing to the diverse implication of carbazole scaffolds in medicinal chemistry, photoelectronic materials and chromophores, the molecules containing the carbazole motif have attracted significant attention over the years. In this work, the vibronic contributions to carbazole structures could facilely change the solvatochromic effect, absorption wavelength, emission wavelength, and Stokes shifts of six 2-carbonyl carbazole ketones fluorophores. Among them, the structure of 1-(1-methyl-9H-carbazol-2-yl)ethanone (3a) were confirmed from single crystal XRD studies. The ratiometric detection of Fe(III) ion of 2-carbonyl carbazole ketone 3a were investigated. Furthermore, it was speculated that chemosensor 3a toward the recognition of Fe3+ cation was dependent on its rigid structure and good coplanarity of the conjugated system, strong intramolecular charge-transfer of 3a.

Synthesis, anticancer evaluation, photophysical properties and molecular docking studies of new thiazolyl-thiadiazolyl ketones (D-π-A structured)

A series of thiazolyl-thiadiazolyl ketones 5a and 5b and their corresponding Schiff’s bases 6a and 6b were synthesized based on the reaction of 2-(2-amino-4-methylthiazol-5-yl)-N-(4-nitrophenyl)-2-oxoacetohydrazonoyl bromide (3) with two types of 2-substituted-3-mercapto-3-(phenylamino)acrylonitrile compounds 4a and 4b. The presence of two potent electron-withdrawing nitrile groups on one side and N,N-dimethylaminobenzylidene moiety on the other side of the thiazolyl-thiadiazolyl ketone 6a promoted maximum UV–Vis absorption. Meanwhile, an in vitro MTT cytotoxicity assay was applied to investigate the activity of the synthesized thiazolyl-thiadiazolyl ketones 5a, 5b, 6a, and 6b on four different cell lines: HepG2, VoLo, MCF-7, and WI38. The cytotoxic possessions were compared to those of the drug reference (Dox). The outcomes revealed varying efficacy towards cancer cell lines, exhibiting cytotoxic selectivity for VoLo and MCF-7. The cytotoxic effectiveness of the thiazolyl-thiadiazolyl ketones revealed good effectiveness, with IC50 values ranging from 11.29 to 22.13 µM. Moreover, the SAR investigation of thiazolyl-thiadiazolyl ketones helped to clarify the reason for their powerful cytotoxic effectiveness. The molecular docking stimulation for the synthesized thiazolyl-thiadiazolyl ketones was looked at against the PDB: 5YJB protein to explore how they bind.

Synthesis of new thiazolyl-thienyl and thiazolyl-thiadiazolyl ketones: Molecular modelling and docking studies as antimicrobial agents

Eight thiazolyl-thienyl and thiazolyl-thiadiazolyl ketones 5a-d and 6a-d were synthesized based on the reaction of 5-(2-bromoacetyl)-4-methyl-2-(methylamino)thiazole (2) and/or N-(4-chlorophenyl)-2-(4-methyl-2-(methylamino)thiazol-5-yl)-2-oxoacetohydrazonoyl bromide (3) with four various thiocarbamoyl compounds 4a-d. The synthesized thiazolyl-thienyl and thiazolyl-thiadiazolyl ketones were optimized using DFT approach offered analogous models in which the thiazolyl, thienyl and thiazolyl nuclei have a planar structure. The HOMO and LUMO of studied hybrids have been consisted mainly of the π- and π*-orbitals of the whole molecule, respectively. Hence, the thiazolyl-thiadiazolyl ketones revealed smaller energy gap (ΔEH-L) than the thiazolyl-thienyl derivatives and may be sorted as 5c < 6c < 6a ≈ 6d < 6b < 5a < 5b < 5d. The antimicrobial activity of synthesized ketones 5 and 6 was examined against representative Gram’s positive and negative bacterial strains along with fungal strains. The amide-thiazolyl thienyl 5d and the nitrile-thiazolyl thiadiazolyl 6a ketones displayed the highest activity against S. aureus and S. pneumoniae, respectively. Conversely, the nitrile-thiazolyl thienyl ketone 5a demonstrated good efficiency against A. fumigatus. Moreover, in-silico molecular docking stimulation was applied to discover the metabolic effectiveness associated to methicillin resistance through the methicillin-resistant strain of Staphylococcus over (PDB:3VSL).

Green synthesis of novel spiropyrazoline-indolinones in neutral deep eutectic solvents and DFT studies

Novel spiropyrazoline-indolinones (4a–t) have been synthesized successfully in neutral deep eutectic solvents by reacting 5-Cl/Br-isatin (1a–b) with aromatic ketones (2a–b) and a variety of substituted hydrazines (3a–e) in good to excellent yields. This eco-friendly straightforward synthetic protocol discloses good functional group compatibility. The conventional synthetic approach was compared with the greener route of microwave-assisted synthesis of spiropyrazolines using ethanol. This approach utilized mild reaction conditions which furnished high yields in short reaction time employing one pot two-step multicomponent. All new compounds were structurally confirmed by detailed spectroscopic analysis and density functional theory calculations. This method provides efficient access to spiropyrazole derivatives using biodegradable and green solvent.

Regio- and stereoselective nucleophilic addition reactions of Swaminathan ketone and its methylated analog using organometallic reagents

Herein, we report the regio- and stereoselective nucleophilic addition reactions of Swaminathan ketone 2a and its methylated analog 2b, both of which contain a 6–7 fused carbocyclic enedione moiety. Nucleophilic additions to 2 using generic organometallic reagents, such as Grignard and organolithium reagents, preferentially occurs at the conjugated carbonyl group to afford a range of tert-alcohols with high stereoselectivity. The selectivity observed with 2 was notable when compared to that observed with Wieland–Miescher ketone 1a bearing a decalin framework. A variety of substituents, such as alkyl, alkenyl, alkynyl and aryl groups, can be introduced into 2 using this method. Exceptionally, the allylation reaction of 2 occurred at both the conjugated and non-conjugated carbonyl groups, but this regioselectivity problem was solved using organocopper reagents.

Biocatalytic Asymmetric Reduction of a Sterically Hindered α-Bromo Ketone for the Synthesis of Key Intermediates of Olodaterol

An efficient and selective biocatalytic process was developed for the reduction of highly bulky and hydrophobic α-bromo ketone 4a using ketoreductase from Lactobacillus kefiri. A fter the initial identification of this selective reductase, reaction conversion was increased from 25.7 to 94.3% and the substrate concentration increased from 5 to 85 g/L via detailed optimization. Through intramolecular epoxidation, the obtained α-bromohydrin 1a was transformed into epoxide 2 as the final product with >99.9% ee, 98.5% HPLC purity, and 90.2% yield over two steps. Eventually, a scale-up demonstration of the telescoped process was successfully performed at a 30 L scale showing excellent reproducibility and consistency, guaranteeing the obtainment of olodaterol with good quality. This biocatalytic process was further demonstrated as environmentally benign by a 50% reduction in process mass intensity (PMI) when compared to the reported (-)-DIP-Cl process.

Synthesis, biological evaluation and molecular docking studies of a new series of bis-chalcones

A convenient and efficient reaction for the synthesis of several new bis-hydroxy derivatives of chalcones 4a–h was accomplished via the two-directional Claisen–Schmidt condensation of different ketones 3a–e with premade benzaldehyde 2 under alkaline conditions. Products were obtained with reasonable yields and with excellent purity. The in vitro antioxidant activity of bis-hydroxychalcones was assessed by DPPH radical scavenging activity in comparison with ascorbic acid, and products showed good antioxidant activity. To determine the possible binding mechanisms with the active site of tubulin and bovine xanthine oxidase (BXO), docking analyses were performed. According to the docking results, compounds 4b and 4a showed the best binding affinity of − 9.13 and − 9.11 kcal/mol for tubulin, respectively. Furthermore, as before, the greatest scores for the case of BXO belong to 4b and 4a with the scores of the values − 10.32 and − 9.81 kcal/mol.Graphical Abstract

Visible-Light-Induced [4+1] Cyclization-Aromatization of Acylsilanes and α,β-Unsaturated Ketones

Visible-Light-Induced [4+1] Cyclization-Aromatization of Acylsilanes and α,β-Unsaturated Ketones

Exploration of Oxidative Ritter-Type Reaction of α-Arylketones and Its Application for the Collective Total Syntheses of Erythrina Alkaloids

Exploration of Oxidative Ritter-Type Reaction of α-Arylketones and Its Application for the Collective Total Syntheses of <i>Erythrina</i> Alkaloids

Tropane-Based Dispirocyclic Oxiranes and Spirocyclic Ketones

AbstractThe Prilezhaev epoxidation of N-Boc-protected 3-cyclobutylidenetropane 1a affords a 1:2 mixture of compounds 2a and 2b, in which tropane and cyclobutane fragments are spiro-connected to the oxirane ring in endo- and exo-fashion, respectively. The exo-isomer 2b is obtained in 89% yield and 97% selectivity via the dioxirane oxidation of 1a. BF3-catalyzed isomerization of exo-oxirane 2b results in a 1:1 mixture of the spirocyclic ketones endo 3a and exo 3b containing spiro-connected tropane and cyclopentanone rings, while endo-epoxide 2a gives exclusively endo-ketone 3a. Prilezhaev and dioxirane epoxidations of N-Boc-protected 3-cyclopropylidenetropane 1b affords a mixture of endo- and exo-oxiranes 2c and 2d. Compounds 2c and 2d are not isolated in individual forms since they isomerize into a mixture of spirocyclic ketones endo 3c and exo 3d. Removal of the Boc groups from ketones 3a–d gives the corresponding hydrochlorides of aminoketones 4a–d in quantitative yields. Quantum chemical calculations predict that the rearrangement of endo-epoxides into the corresponding endo-ketones involving BF3-containing intermediates has by 4.4–7.9 kcal/mol lower activation barriers than the respective conversion of the exo-epoxides into exo-ketones. The cyclopropyl-containing dispiroepoxides 2c and 2d are predicted to interconvert faster into the corresponding ketones compared to their less strained cyclobutyl counterparts 2a and 2b.

A base-controlled switch of SO2 reincorporation in photocatalyzed radical difunctionalization of alkenes

A base-controlled switch of SO2 reincorporation in photocatalyzed radical difunctionalization of alkenes

Bifunctionalization of α,β-unsaturated diaryl ketones into α-aryl-β,β-ditosyloxy ketones: Single crystal XRD, DFT, FMOs, molecular electrostatic potential, hirshfeld surface analysis, and 3D-energy frameworks

Environmentally benign synthesis, structural explication by means of IR, 1H & 13C NMR, HRMS and crystal structure of two electronically different α-aryl-β,β-ditosyloxy ketones i.e., 2-(4-methylphenyl)-3-oxo-3-phenylpro- pane-1,1-diyl bis(4-methylbenzenesulfonate) (C30H28O7S2) (5a) and 3-(4-fluorophenyl)-2-(4-methoxyphenyl)-3-oxopropane-1,1-diyl bis(4-methylbenzene- sulfonate) (C30H27FO8S2) (5b) have been successfully described here. Both α-aryl-β,β-ditosyloxy ketones 5a and 5b crystallized in the monoclinic crystal system with P21/n and P21/c space group respectively. Single crystal XRD-analysis unraveling the oxidative skeletal rearrangement in α,β-unsaturated diaryl ketones and outcome of reaction introduced the synthetic community with still unrecognized and excellent 1,3-dielectrophilic precursors i.e., α-aryl-β,β-ditosyloxy ketones. Density functional theory (DFT), HOMO-LUMO, 3D-hirshfeld surface analysis, 2D-finger plots, molecular electrostatic potential (MEPs) and 3D-interaction energies have been performed and discussed with an objective to study the physical properties of these new 1,3-dielectrophilic three carbon atom components before their utilization as a chemical precursor in heterocycles synthesis like α,β-dibromo analogues.

One-Pot Synthesis of Some New s-Triazole Derivatives and Their Potential Application for Water Decontamination.

A rapid, efficient, and one-pot protocol has been developed for the synthesis of cyclized 2,6-dimethyl-5-substituted-thiazolo[3,2-b]-s-triazoles (3a–c) through the interaction of 5-methyl-1H-s-triazole-3-thiol (1) with aliphatic ketones (2a–d) in refluxing acetic acid in the presence of a catalytic amount of sulfuric acid (AcOH/H+) while with aromatic ketones (5a–d), a mixture of uncyclized 3-methyl-s-triazolylthioacetophenone derivatives (6a–d) and cyclized 6-aryl-2-methyl-thiazolo[3,2-b]-s-triazoles (7a–d) has been produced. With this catalytic system, inexpensive sulfuric acid was utilized as a catalyst, which prevented the production of poisonous and irritating halo carbonyl compounds. On the other hand, the interaction of s-triazole 1 with cyano compounds (9a,b) afforded the corresponding 6-amino-2-methyl-5-substituted-thiazolo[3,2-b]-s-triazoles (10a,b). Similarly, treatment of 4-amino-3-methyl-s-triazole-5-thiol (12) with aliphatic and aromatic ketones (2c and 5a–e) afforded directly 3-methyl-7H-s-triazolo[3,4-b]-1,3,4-thiadiazines (13a and 14a–e). Further, reaction of 12 with cyano compounds (9a,b) under the same reaction conditions yielded the corresponding 3-methyl-s-triazolo[3,4-b]-1,3,4-thiadiazole derivatives (15a,b). The reaction mechanism was studied, and the structures of all novel compounds were verified using spectroscopy and elemental analysis. Moreover, the potential application of the synthesized compounds toward heavy metal ions and inorganic anion removal from aqueous solution has been investigated. The removal effectiveness for metal ions reached up to 76.29%, while for inorganic anions it reached up to 100%, indicating that such synthesized compounds are promising adsorbents for water remediation.

A DFT study on the mechanism and selectivity of [3 + 2] cycloaddition reactions leading to pyrole[2,1-a] phthalazine compounds

The mechanism of [3 + 2] cycloaddition (32CA) reactions of phthalazinium-2-dicyanomethanide with electron-deficient and electron-rich ethylenes has been studied using density functional theory (DFT) methods at the M06-2X/cc-pVDZ level of theory. The energy results indicated that the regio- and stereoselectivity of the two 32CA reactions oppose one another, which is in agreement with the experimental report. Accordingly, in the 32CA reaction of phthalazinium-2-dicyanomethanide 1 with methyl vinyl ketone 2a, an electron poor dipolarophile, the meta/endo pathway was more stable than others, while the ortho/exo pathway was the most stable for the 32CA reaction of phthalazinium-2-dicyanomethanide 1 with 1-methoxy-4-vinyl benzene 2b, an electron-rich dipolarophile. Moreover, DFT reactivity indices were studied for the reagents to explain the nucleophilicity and electrophilicity of reagents and selectivity of the reactions. The electron rearrangements along the preferred pathways of these 32CA reactions were studied using the topological analysis of the electron localization function (ELF). The ELF analysis revealed that the reactions proceed through a two-stage one-step mechanism. The noncovalent interactions topological analysis of the possible pathways of the reactions revealed that in addition to strong attractive and repulsive interactions, the weak non-covalent interactions and the steric repulsive interactions have important roles in the determination of the preferred regio- and stereoselective pathway.

New Photochromic α-Methylchalcones Are Highly Photostable, Even under Singlet Oxygen Conditions: Breaking the α-Methyl Michael-System Reactivity by Reversible Peroxybiradical Formation.

The α-methylated chalcones 7a–7e behave as P-type photochromic substances with photo-stationary states (PSS) as high as 15:85 when irradiated at 350 nm. These compounds are easily accessible in pure E-configuration by aldol condensation or by oxidative coupling/elimination. The α-methyl groups make these compounds potentially reactive with singlet oxygen following the gem-rule that predicts 1O2 regioselectivity. Even after long irradiations times in the presence of the singlet oxygen sensitizer tetraphenylporphyrin (TPP) and oxygen, however, no oxygenation products were detected. Under these conditions, all substrates were converted into 9:1 E/Z-mixtures despite the use of low-energy light that does not allow direct or sensitized excitation of the substrates 7. Additionally, chalcone 7a reduced the singlet oxygen reactivity of the tiglic ketone 3a by about a factor of two, indicating substantial physical quenching of singlet oxygen by the α-methylated chalcones 7a–7e. Thus, a singlet oxygen-induced E/Z-isomerization involving 1,2-dioxatetra-methylene biradicals that leads to triplet oxygen and thermodynamic E/Z-mixtures is postulated and supported by quantum chemical (DFT)-calculations.

Regioselective synthesis and evaluation of novel sulfonamide 1,2,3-triazole derivatives as antitumor agents

A novel series of 1,2,3-triazole containing sulfonamide moiety was synthesized. Treatment of 4-acetyl 1,2,3-triazole 3 with different aldehydes gave α,β-unsaturated ketones 4a–c. Condensation of 3 with dimethylformamide dimethylacetal (DMF-DMA) gave formimidamide 5. Chalcone 7 was achieved via two ways from the reaction of 5 with benzaldehyde or from treatment of 4a with DMF-DMA. Reaction of 7 with hydrazine hydrate afforded pyrazoline 8. 5-Methyl pyrazole 12 was synthesized from Claisen condensation reaction of 3 or 5 with ethyl acetate to give 1,3-diketone adduct 9 or 10, respectively, followed by treatment with hydrazine hydrate. 5-Aminopyrazole 17 was synthesized from the reaction of ester 13 or formimidamide ester 13a with acetonitrile to afford cyanoacetyl derivatives 14 or 15, respectively, followed by treatment with hydrazine hydrate. The new compounds were screened for their in vitro antitumor activity. The results of this investigation revealed that compounds 12, 7, and 17 had a significant anticancer activity against MCF-7 cancer cell line with IC50 values 12.4, 19.8, and 23.4 µM, respectively, in relation to the standard drug, doxorubicin.

Synthesis, cytotoxic activity, ADMET and molecular docking study of quinoline-based hybrid compounds of 1,5-benzothiazepines

Some α,β-unsaturated ketones 4a–g of 3-acetyl-4-hydroxyquinolin-2(1H)-one were prepared and converted into a series of new hybrid compounds, quinoline-benzothiazepine 6a–g. Compounds 6d and 6g had the best activity against HepG2 and KB cell lines.

Synthesis and Molecular Modeling Studies on Novel C2 Alkylated Benzoazonine Scaffold and Corresponding 2-Pyrazoline Derivatives as Acetylcholinestrase Enzyme Inhibitors

A rapid and efficient methodology was performed for the synthesis of α,β-unsaturated ketones 2a–k containing benzoazonine core through Claisen-Schmidt reaction of the benzoazonine-2,7-dione 1 and various aldehydes in acidic medium. The obtained exocyclic α,β-unsaturated ketones were subjected to an irradiating microwave gave unexpected asymmetric spiro pyran compound 3 via a self-Diels–Alder reaction. The initially formed exocyclic α,β-unsaturated ketones underwent cyclocondesation with phenylhydrazine to afford 2-pyrazoline derivatives 4. The structure of the synthesized scaffolds was characterized using 1H-NMR, APT and 2DNMR spectra. A molecular modeling study using Molecular Operating Environment was performed to investigate their binding modes to the Acetylcholinestrase enzyme active site. Docking results demonstrated that the newly synthesized compounds recognized the active sites of Acetylcholinestrase and form different types of bonding interactions with key active site amino acid residues.