Ketones Research Articles

In-situ DRIFTS insights into the evolution of surface functionality of biochar upon thermal air oxidation

Biochar surface functionality is crucial for its application. Herein, the evolution of biochar surface functionality upon thermal air oxidation (TAO) was investigated in-situ by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and thermogravimetric analysis (TGA). The results show that, although the surface functionality of biochar is remarkably changed during TAO at the initial low temperature range, the biochar weight is still stable in the initial low temperature range, suggesting the chemisorption of O2 as intermediate oxygenated functional groups (OFGs) on biochar surface. Moreover, the evolution of biochar surface functionality upon TAO is highly affected on its preparation temperature and intrinsic minerals. Specifically, biochar produced at a high temperature is more resistant to TAO, and more favorable for the formation of ketone groups during TAO. While the biochars prepared at low or medium temperatures show a remarkable formation of carboxyl/lactone groups upon TAO, and the maximum temperature for the formation of carboxyl/lactone groups can be achieved at 400 °C. It's worth noting that the intrinsic minerals in biochar catalyze the TAO reaction, resulting in a much higher mass loss of biochar upon TAO. Furthermore, with the catalysis of intrinsic minerals, TAO is more suitable for enhancing the performance of biochar with intrinsic minerals. These results facilitate the design of engineered biochar via TAO for enhanced applications.

Highly efficient lignin depolymerization and enhanced bio-oil upgrading via in-situ hydrogenation: Impact of lignin structure

The inherent structural rigidity of lignin poses a significant challenge to its direct hydrogenation to produce aromatic compounds, requiring harsh reaction conditions. In this study, microwave-assisted hydrothermal liquefication was employed to rapidly generate raw bio-oil under mild conditions, coupled with an in-situ hydrogenation strategy to upgrade its quality. A series of lignin substrates were characterized to establish the relationship between lignin characteristics and aromatic products. Grass lignin can produce low molecular weight bio-oil in high yields (50.4–60.7 %) within 30 min at 180 °C, which is attributed to the abundance of cleavable β-O-4 linkages in its uniform structure. In contrast, softwood lignin with abundant guaiacyl (G) units possessed a robust thermal stability, resulting in a low monomer yield, but a high selectivity to G-type products (97 %). The raw bio-oil was further upgraded through in-situ hydrogenation with Pd catalysts. Low reaction temperatures (60–100 °C) favored the hydrogenation of aromatic aldehydes and ketones to their alcohol products, while high temperatures (100–220 °C) promoted the deep hydrogenation of aromatic side chains to alkyl products. Besides, an upgraded bio-oil with a higher heating value (29.8 MJ/kg) was obtained. Furthermore, the hydrogenation mechanism was investigated through the kinetics of simulated bio-oils. The activation energy follows the order: dimer β-O-4 linkage < monomer aldehyde group < ketone group < CC linkage, which is consistent with the hydrogenation kinetics observed in real lignin bio-oil. Overall, this study highlights the impact of lignin characteristics on subsequent conversion and alsoenhances our understanding of the complex depolymerization/hydrogenation mechanisms during lignin upgrading.

Crucial role of nitrogen vacancies in carbon activated persulfate toward nonradical abatement of micropollutants from secondary effluent

Biomass-derived carbonaceous materials exhibit fascinating potentials in nonradical oxidation of micropollutants (MPs) by activating persulfate and their performances mainly rest on graphitic N. However, the simultaneously derived N vacancy received little attention. Herein, a graphene-like material rich in N vacancy was synthesized from coffee residues. It showed excellent removal efficiency (95 %) and degradation kinetics (0.21 min−1) in abating tetracycline antibiotics from secondary effluent and significant biotoxicity was diminished. Solid nonradical oxidation consisting of electron transfer (89 %) and singlet oxygen (1O2) oxidation (11 %) was determined. By tracking 1O2 source and electron flow, ketone group appeared at N vacancy was found as the critical site to grab electrons from peroxydisulfate (PDS) with production of 1O2. Then the electrons were transferred to graphitic N driven by the microelectric field between them. This work notices the function of vacancies in biomass resources for high-efficient removal of MPs from real water matrix.

One‐Pot Synthesis of 3‐Hydroxy‐1H‐Pyrrolo[3,4‐b]quinolin‐1‐one via Enaminamides

AbstractA multicomponent cascade cyclization reaction using aryl methyl ketones, aryl amines, and enaminamide reagents to construct 3‐hydroxy‐1H‐pyrrolo[3,4‐b]quinolin‐1‐one skeleton with good substrate compatibility (50 examples) has been reported. The one‐pot, metal‐free process formed two C−C bonds, two C−N bonds, and a tetrasubstituted carbon stereocenter containing a hydroxyl group. The reaction enabled modified transformation of drug molecules and derivatization of products.

Microcystin-RR is a biliary toxin selective for neonatal extrahepatic cholangiocytes

BACKGROUND AND AIMSBiliary atresia is a fibrosing cholangiopathy affecting neonates that is thought to result from a prenatal environmental insult to the bile duct. Biliatresone, a plant toxin with an α-methylene ketone group, was previously implicated in biliary atresia in Australian livestock, but is found in a limited location and is highly unlikely to be a significant human toxin. We hypothesized that other unsaturated carbonyl compounds, some with the potential for significant human exposure, might also be biliary toxins. METHODSWe focused on the family of microcystins, cyclic peptide toxins from blue-green algae that are found worldwide, particularly during harmful algal blooms. We used primary extrahepatic cholangiocyte spheroids and extrahepatic bile duct explants from both neonatal (a total of 86 P2 mouse pups and 18 P2 rat pups (n=8-10 per condition for both species)) and adult rodents (a total of 31 P15-18 mice (n=10-11 per condition)) to study the biliary toxicity of microcystins and potential mechanisms RESULTSWe found that 400 nM microcystin-RR, but not six other microcystins or the related algal toxin nodularin, caused greater than 80% lumen closure in cell spheroids made from extrahepatic cholangiocytes isolated from 2-3-day-old mice (p<0.0001). In contrast, it resulted in less than an average of 5% lumen closure in spheroids derived from neonatal intrahepatic cholangiocytes or cells from adult mice (p=0.4366). We also found that microcystin-RR caused occlusion of extrahepatic bile duct explants from 2-day-old mice (p<0.0001), but not 18-day-old mice. Microcystin-RR caused a 2.3 times increase in reactive oxygen species in neonatal cholangiocytes (p<0.0001), and treatment with N-acetyl cysteine partially prevented microcystin-RR-induced lumen closure (p=0.0004), suggesting a role for redox homeostasis in its mechanism of action. CONCLUSIONSWe identify microcystin-RR as a selective neonatal extrahepatic cholangiocyte toxin and suggest that it acts by increasing redox stress.

Recent Development on the Heterocycles Derived From In Situ Formation of Aryl Glyoxals by Iodine/DMSO Mediated Oxidation of Methyl Ketones

ABSTRACTControlled oxidation of methyl‐ketones to aryl glyoxals using Selenium dioxide and iodine is one of the useful transformation. Regardless the availability of many oxidation reagents, Iodine/DMSO system is very efficient and flexible. This system efficiently allows in situ formation of α‐halo ketones and subsequently transforming them directly to useful products. The Iodine/DMSO system allows the selective CI and CO bond formation, substantially useful for converting them to other bond forming reactions and heterocycles useful in the synthetic and medicinal chemistry. Iodine/DMSO system could be an important alternative strategy due to sustainability, metal‐free conditions, allowing multiple/linear domino reactions. This review will focus on heterocyclic systems smartly developed/manipulated by Wu group from methyl‐ketones. The scope and limitations of this method and selected examples of applications for the synthesis of interesting molecules are discussed herein.

Altechromone A Ameliorates Inflammatory Bowel Disease by Inhibiting NF-κB and NLRP3 Pathways.

Altechromone A, also known as 2,5-dimethyl-7-hydroxychromone, is a hydroxyketone containing one hydroxyl and one ketone group. In this study, we isolated Altechromone A from the marine-derived fungus Penicillium Chrysogenum (XY-14-0-4). Previous reports show that Altechromone A has various activities including tumor suppression, antibacterial, and antiviral activities. However, there is no study about its anti-inflammatory activity in inflammatory bowel disease (IBD). Here, we assess the anti-inflammatory activity, especially in IBD, and its potential mechanism using the zebrafish model. Our results indicated that Altechromone A has anti-inflammatory activity in a CuSO4-, tail-cutting-, and LPS-induced inflammatory model in zebrafish, respectively. In addition, Altechromone A greatly reduced the number of neutrophils, improved intestinal motility and efflux efficiency, alleviated intestinal damage, and reduced reactive oxygen species production in the TNBS-induced IBD zebrafish model. The transcriptomics sequencing and real-time qPCR indicated that Altechromone A inhibited the expression of pro-inflammatory genes including TNF-α, NF-κB, IL-1, IL-1β, IL-6, and NLRP3. Therefore, these data indicate that Altechromone A exhibits therapeutic effects in IBD by inhibiting the inflammatory response.

In Silico Structure-Activity Study of Selected Triterpenoids as Potential Inhibitors of Mycolic Acid Transporter of Mycobacterial MmpL3 Receptor Protein

Structural features of the triterpenoid skeleton that are necessary for antimycobacterial activity are not well understood. Following the isolation of the triterpenoids ergosterol-5,8-endoperoxide, 6β-hydroxykulactone, 12β-hydroxykulactone, (24R)-24,25-epoxycycloartan-3-one and (3β,24R)-24,25-epoxycycloartan-3-ol, and (3β,24R)-24,25-epoxycycloartan-3-acetate with varying antimycobacterial activity ranging between MIC of 1 µg/ml to128 µg/ml prompted us to study this class of compounds further to shade light on the structural features necessary for their antimycobacterial activity. This in silico study involved docking the triterpenoids on the mycobacterial multi-pharmacophore receptor protein MmpL3. The docking results were compared with the MmpL3 receptor protein co-crystallized TB drug candidate, AU1235, (1-(2-adamantyl)-3-[2,3,4-tris(fluoranyl)phenyl] urea). The virtual screening revealed key structural features in the triterpenoid skeleton, including the C-3 keto and β-hydroxy group on C-3 or C-6, as important for antimycobacterial activity. Also, the decreased binding affinity for compounds 2 and 7 with an acetate group on C-3 were in tandem with those observed in vitro. Toxicity predictions revealed that this class of compounds had no mutagenic effects and displayed favorable pharmacokinetic parameters. The study reveals the potential of the triterpenoid skeleton exemplified by the readily available ergosterol-5,8-endoperoxide as a useful scaffold in searching and developing effective therapeutic lead entities to facilitate anti-tuberculosis drug discovery.

Strain‐Release‐Driven Modular Synthesis of Oxetane‐Based Amide Bioisosteres: Concise, Robust and Scalable Approach

AbstractAmide bioisoterism is a widely used strategy in drug development to fine‐tune physicochemical, pharmacokinetic, and metabolic properties, eliminate toxicity and gain intellectual property rights in uncharted chemical space. Of these, oxetane‐amines offer particularly exciting possibilities as bioisosteres, although they are less frequently investigated than warranted due to the lack of simple and widely applicable synthetic methods. Herein, we report a two‐step, practical, modular, robust, and scalable method for the construction of oxetane‐containing amide bioisosteres that relies on the readily available oxetan‐3‐one. This operationally simple procedure exploits the enhanced reactivity of the keto group of the commercially available oxetan‐3‐one to form amine‐benzotriazole intermediates, which springloaded adducts are then reacted with various aliphatic and aromatic organometallic reagents under mild conditions to afford various amino‐oxetanes in good to high yields. The simplicity and broad applicability of the method greatly facilitates the synthesis of derivatives that were previously difficult or impossible to produce. The usefulness of this method in the field medicinal chemistry was also demonstrated by eliminating the well‐known metabolic problem of ketoconazole.

Elevated blood-ethanol concentration promotes reduction of aliphatic ketones (acetone and ethyl methyl ketone) to secondary alcohols along with slower oxidation to aliphatic diols.

Many people convicted for drunken driving suffer from an alcohol use disorder and some traffic offenders consume denatured alcohol for intoxication purposes. Venous blood samples from people arrested for driving under the influence of alcohol were analyzed in triplicate by headspace gas chromatography (HS-GC) using three different stationary phases. The gas chromatograms from this analysis sometimes showed peaks with retention times corresponding to acetone, ethyl methylketone (2-butanone), 2-propanol, and 2-butanol in addition to ethanol and the internal standard (1-propanol). Further investigations showed that these drink-driving suspects had consumed an industrial alcohol (T-Red) for intoxication purposes, which contained > 90% w/v ethanol, acetone (~ 2% w/v), 2-butanone (~ 5% w/v) as well as Bitrex to impart a bitter taste. In n = 75 blood samples from drinkers of T-Red, median concentrations of ethanol, acetone, 2-butanone, 2-propanol and 2-butanol were 2050mg/L (2.05g/L), 97mg/L, 48mg/L, 26mg/L and 20mg/L, respectively. In a separate GC analysis, 2,3-butanediol (median concentration 87mg/L) was identified in blood samples containing 2-butanone. When the redox state of the liver is shifted to a more reduced potential (excess NADH), which occurs during metabolism of ethanol, this favors the reduction of low molecular ketones into secondary alcohols via the alcohol dehydrogenase (ADH) pathway. Routine toxicological analysis of blood samples from apprehended drivers gave the opportunity to study metabolism of acetone and 2-butanone without having to administer these substances to human volunteers.

Synthesis and Molecular Modeling Studies and In silico Anthelmintic Activity of N-(benzo[d]thiazol-2-yl)-3- Chloro-6-Nitrobenzo[b]thiophene- 2-Carboxamide Derivatives

Helminthiasis is a noteworthy health problem with increased morbidity. In this manuscript, we developed a series of N-(benzo[d]thiazol-2-yl)-3-chloro-6-nitrobenzo[b]thiophene-2-carboxamide derivatives (3a-f) and evaluated against Pheretima posthuma and Perionyx excavates helminths. The compounds 3a-f were synthesized by reaction of 3-chloro-6-nitrobenzo[b]thiophene-2-carbonyl chloride (1) and appropriate benzo[d]thiazol-2-amines (2a-f) presence of pyridine. A compound 1 was synthesized by reaction of 4-nitro-cinnamic acid reacts with thionyl chloride in the presence of pyridine and chlorobenzene. Results showed that molecule 3c observed with maximum anthelmintic against P. excavates and P. posthuma with mean paralyzing time of 13.15 min and 17.39 min and mean death time of 16.17 min and 20.14 min, respectively. Molecular docking against 3VRA receptor showed that molecule 3c showed maximum dock score of -7.3 kcal/mol and reference standard albendazole with dock score of -5.5 kcal/mol. Molecular dynamic simulation data reflected the stable ligand-receptor interaction. As per Molecular Mechanics Poisson-Boltzmann Surface Area analysis, maximum free binding energy of -31.224 kJ/mol showed by 3c and ARG 76 was the most contributed residue. Density functional theory calculation data confirmed that most of the molecules were soft molecules with electrophilic nature. Molecular electrostatic potential data of 3c showed that terminal nitro group, ketone group, -COO group of ester were responsible for electrophilic attack and benzo[b]thiophne and -NH groups were responsible for nucleophilic attack. The activity profile of the synthesized molecules against helminthes was 3c &amp;gt;3e &amp;gt;3d &amp;gt;3f &amp;gt;3b &amp;gt;3a.. KEYWORDS :Molecular docking, Molecular dynamic simulation, Molecular mechanics poisson-boltzmann surface area, Density functional theory, Anthelmintic activity.

Coupling photocatalytic trifluoromethylation with biocatalytic stereoselective ketone reduction in continuous flow

Photocatalysis and biocatalysis represent powerful efficient tools in synthetic chemistry. While, both have individually shown promising results, their integration remains challenging, particularly in continuous flow processes. This work presents a semicontinuous setup, combining photo- and biocatalysis in a multistep synthesis for the production of optically pure (S)-3,3,3-trifluoro-1-phenylpropan-1-ol. Initially, a photocatalytic trifluoromethylation of a methyl ketone in α-position in a self-made photoreactor was tested in flow, followed by enzymatic ketone reduction catalyzed by an alcohol dehydrogenase (variant of an ADH from Lactobacillus kefir). The study addresses the challenge of enzyme stability in aggressive solvents, developing a robust immobilization approach for the selected ADH with a PVA/PEG cryogel matrix. This strategy has been investigated in this work to ensure enzyme stability in THF, marking a notable advance in compatibility for continuous cascades. The separate process steps were finally combined in a semicontinuous flow system, achieving a space–time yield for the photocatalytic step of 39.8 g L−1 h−1 and of 1.12 g L−1 h−1 for the enzymatic step. The study signifies one of the first instances of combining photo- and biocatalysis in continuous cascades, offering an innovative approach to synthesizing chiral 3,3,3-trifluoro-1-phenylpropan-1-ol.Graphical abstract

Analyze and assess the spectral, DFT, and medicinal characteristics through targeted pharmacological investigation of 2-(3-(5-(4-chlorophenyl)furan-2-yl)acryloyl)-3,4-dihydro-2H-naphthalen-1-one (CHFADN)

The compound 2-(3-(5-(4-chlorophenyl)furan-2-yl)acryloyl)-3,4-dihydro-2H-naphthalen-1-one (CHFADN) was synthesized using the Claisen-Schmidt condensation method, reacting aromatic aldehydes with methyl ketones. Characterization was performed using NMR, FTIR, and UV–visible spectroscopy. A theoretical model was developed with Gaussian 09 software, utilizing the B3LYP/6–311++G(d,p) basis set, to investigate geometric, electronic, and spectroscopic properties, including geometry optimization, harmonic vibration simulations, molecular electrostatic potential (MEP), frontier molecular orbitals (FMOs), and Mulliken's population analysis. A scaling factor of 0.9600 ensured alignment between the compound's vibrational spectrum and the experimental IR spectrum.In-vitro testing showed notable bactericidal efficacy,H2O2 scavenging activity and antidiabetic activity. In silico molecular docking using AutoDock 4.0, focusing on the 1HD2 protein's active pocket, revealed a binding interaction energy of -6.5 kcal/mol. ADME properties were predicted based on retention data (RM0). The compound showed no mutagenic effects in toxicity testing, indicating a promising safety profile for new drug candidates.

TfOH-Catalyzed Reactions of Aryl Methyl Ketones with Ynamides: Synthesis of 1-Amino-1H-indenes and 2,4-Dienamides.

The efficient synthesis of 1-amino-1H-indenes and 2,4-dienamides was realized via TfOH-catalyzed reactions of aryl methyl ketones with terminal ynamides in two distinct pathways. Aromatic ketones with high electrophilicity underwent [3 + 2] annulation with ynamides to produce 1-amino-1H-indenes, while aromatic ketones with low electrophilicity proceeded under the same conditions to afford 2,4-dienamides. Furthermore, the obtained 1-amino-1H-indenes could be converted into the corresponding 1H-indenes and dihydro-1H-indenes in excellent yields.

Iodine-promoted sequential C(sp3)-H oxidation and cyclization of aryl methyl ketones with 2-(2-aminophenyl)quinazolin-4(3H)-ones.

An I2-promoted, metal-free protocol has been developed for the one-pot synthesis of 6-aroyl-5,6-dihydro-8H-quinazolino[4,3-b]quinazolin-8-ones from readily accessible substrates. This reaction involves the in situ sp3 C-H oxidation of aryl methyl ketones to phenylglyoxal, followed by imine formation and intramolecular nucleophilic addition, resulting in the formation of two new C-N bonds. Furthermore, the method is applicable to a wide range of aryl methyl ketones, including heterocycles and drug-derived substrates, yielding the desired products with yields ranging from 62% to 93%. Additionally, the practical utility of this approach was demonstrated through gram-scale synthesis.

Fully biobased unsymmetric bisphenols from condensation of lignin-derived monophenols for non-isocyanate polyurethane synthesis

Transforming renewable biomass and CO2 to the high value-added non-isocyanate polyurethanes (NIPUs) was of great significance to the development of sustainable chemistry. Herein, a series of unsymmetric bio-based bisphenols featured with chalcone structure were designed and synthesized by Claisen-Schmidt condensation of lignin-derived monophenols (vanillin and syringaldehyde) and plant methyl ketones (zingiberone, raspberry ketone, and piceol), these phenols and ketones are value-added chemicals from biorefinery process of biofuels. The unsymmetric bio-based bisphenols were consequently transformed into bis-epoxides, bis(cyclic carbonate)s, and finally polyhydroxyurethanes (PHUs). With eco-friendly proline as the catalyst, bio-based bisphenols were prepared in excellent yields (76% − 95%). More than 90% isolated yields of bis(cyclic carbonate)s were obtained from bis-epoxides. All of the bis(cyclic carbonate)s were cured with long-chain amine, i.e. PriamineTM 1074, and the result PHUs, a kind of NIPUs, have thermal stability comparable to bisphenols A-based network according to DSC and TGA. The attempts to one-pot-two-step synthesis of PHUs also exhibited better thermal properties, which bis-epoxides directly conducted successively with carbon dioxide and 1,6-hexamethylenediamine. The bio-based bisphenols appeared to be a promising substitute to bisphenols-A with the aim at synthesizing environmentally friendly PHUs. Therefore, this study provided a valuable route in utilization of carbon dioxide and functional aromatics from fuel process into fully biobased polymeric materials.

Regioselective Annulation of 3(5)‐Aminopyrazole with Aryl Ketones or Aryl Alkynes Using N,N‐Dimethylethanolamine as a Single/Triple Carbon Synthon

AbstractAn efficient and regioselective cyclization for construction of pyrazolo[3,4‐b]pyridines and methylene‐bridged bis(pyrazolo[1,5‐a]pyrimidines) has been established. It involves a [3+2+1] annulation of 3(5)‐aminopyrazole, N,N‐dimethylethanolamine (DMEA), with 1,2‐insertion of aryl methyl ketones or 2,1‐insertion of aryl alkynes. DMEA is oxidized through C(sp3)‐H activation to provide a single or triple carbon source.

An In-Depth Exploration of Six Decades of the Kröhnke Pyridine Synthesis.

The Kröhnke Pyridine Synthesis has been discovered about six decades ago (1961), by Fritz Kröhnke and Wilfried Zecher at the University of Giessen. The original method involved the reaction of α-pyridinium methyl ketone salts with α,β-unsaturated carbonyl compounds in the presence of a nitrogen source, frequently ammonium acetate. Since its discovery, the Kröhnke methodology has been demonstrated to be suitable for the preparation of mono-, di-, tri- and tetra-pyridines, with important applications in several research fields. Over the years, a number of modifications to the original approach have been developed and reported, enabling for the broad applicability of these methods even in modern days, also for the synthesis of non-pyridine compounds. In this critical and tutorial review, we will thoroughly explore and discuss the potential of the original method, the refinements that have been made over the years, as well as some applications arising from each type of pyridine and/or non-pyridine compounds produced by Kröhnke's approach.

Investigation Towards the Asymmetric CBS‐Catalysed Reduction of Aryl Methyl Ketones with Electrochemically in Situ Generated BH3

AbstractThe aim of this investigation was to explore the possibility to perform an asymmetric reduction, utilising a CBS‐type catalyst, of prochiral aryl methyl ketones under electrochemical conditions to generate the needed BH3 upon oxidation of NaBH4 with in situ generated I2 in the anode compartment. Therefore, various electrochemical parameters were optimised to conduct the desired formation of the chiral secondary alcohols in high to quantitative yields with a high stereochemical induction, although the catalyst loading had to be chosen relatively high to concur with the racemic reduction of the ketones by the electrogenerated BH3.

Modeling Electrochemical Vacancy Regeneration in Single-Walled Carbon Nanotubes.

Synthesis-induced defects in single-walled carbon nanotubes (SWCNTs) enable diverse catalytic reactions, but the nature of catalytic intermediates and how active species regeneration occurs are unclear. Using a quantum mechanics/molecular mechanics (QM/MM) hybrid methodology based on density functional theory (DFT) and a classical force-field, we explore the reactivity and electrochemical regeneration of a vacancy defect in a zigzag SWCNT. Our findings indicate that hydrolysis of the defect forms a ketone group on one carbon atom and C-H bonds on two adjacent carbons. Applying an electrochemical potential of ESHE = -0.740 V triggers a proton-coupled electron transfer (PCET), converting the ketone to a hydroxyl group. Further reduction at ESHE = -1.08 V induces another PCET, expelling the hydroxyl as water and forming an active carbon with carbene character that can react with hydrogen peroxide and perchlorate. The hydrogen atoms on neighboring carbons prevent further water dissociation, maintaining the catalytic vacancy.