Alkyl Ketones Research Articles

Photoreductive N-N Homocoupling Catalyzed by a Superphotoreductant.

Azines are valuable synthons or target molecules in organic synthesis. In this work, we report that CBZ6 could work as a photoreductive catalyst for the N-N homocoupling of oximes in high efficiency. This therefore enabled convenient access to a large variety of azines from the corresponding aryl and alkyl ketones, as well as aryl aldehydes in up to 99% yield. 2,4-Dinitrophenoxyl was used as the recyclable auxiliary and the CBZ6 photocatalyst could also be recycled. These together with the low catalyst loading (2 mol % of CBZ6), the short reaction time (4 h), and the nontoxic DMSO solvent make the current process a sustainable and practical alternative to the classic methods.

Cu12-Methylsilsesquioxane Cage Decorated with Cu(dppe)2 Moieties for Mild Oxidative Functionalization of Alkanes.

We report a high nuclear (Cu14) complex synthesized via the self-assembly of copper-methylsilsesquioxane induced by the complexation with 1,2-bis(diphenylphosphino)ethane (dppe). The structure includes two cationic CuI(dppe)2 moieties and an anionic silsesquioxane cage of an unprecedented CuII12 structural type. The Cu12 cage fragment exhibits a unique (i) combination of Si4-cyclic/Si2-acyclic silsesquioxane ligands and (ii) encapsulation of two different chloride and carbonate species. This complex acts as a promising precatalyst in the mild oxidation and carboxylation of light alkanes to produce alkyl hydroperoxides, alcohols, ketones, or carboxylic acids. The present study widens the family of copper-methylsilsesquioxane clusters with prospective use in oxidation catalysis.

Glucose hydrochar consists of linked phenol, furan, arene, alkyl, and ketone structures revealed by advanced solid-state nuclear magnetic resonance

The molecular structure of hydrochars produced from 13C-enriched glucose under various conditions has been elucidated based on advanced one- and two-dimensional (2D) 1H-13C and 13C–13C solid-state nuclear magnetic resonance (NMR) with spectral editing. Regardless of synthesis conditions, hydrochars consist mostly of oxygen-substituted arene rings (including diphenols) and furans connected by alkyl linkers rich in ketones. Cross-linking nonprotonated and methyne (C-H) alkyl carbons have been identified through spectrally edited 2D NMR. Alkenes and ‘quaternary’ C-O are observed only at low synthesis temperature, while some clusters of fused arene rings are generated at high temperature. Hydrochar composition is nearly independent of reaction time in the range from 1 to 5 h. Equilibration of 13C magnetization within 1 s shows that the materials are homogeneous on the 5-nm scale, refuting core–shell models of hydrochar microspheres. While furan C-O carbons bonded to alkyl groups or ketones show distinctive cross peaks in 2D NMR, phenolic C-OH is observed unambiguously by hydroxyl-proton selection. While methylene-linked furan rings are fairly common, the signal previously assigned to furan Cα-Cα linkages is shown to arise from abundant, stable catecholic ortho-diphenols, whose HO-C=C-OH structure is proved by 2D13C–13C NMR after hydroxyl-proton selection. Quantitative 13C NMR spectra of low- and high-temperature hydrochars have been matched by chemical-shift simulations for representative structural models. Mixed phenol and furan rings connected by ketones and alkyl linkers provide good fits of the experimental spectra, while literature models dominated by large clusters of fused rings and with few phenols or alkyl-linked ketones do not.

Water Participated Dual C(sp3)−C(sp3) Bond Cleavage of Cyclobutanones Catalyzed by Lewis Acid

AbstractLewis acid‐catalyzed ring‐opening reactions of cyclobutanones were mostly achieved through cleavage of a single C2−C3 bond to deliver cyclic products. Herein, an unprecedented Lewis acid catalyzed synergistic cleavage of both C2−C3 bonds in 3‐arylcyclobutanones was realized under participation of water, providing a series of aryl alkyl ketones in mild conditions. A broad scope of substrates decorated with various substituents were well accommodated. Mechanistic proposal including the function of water was unambiguously validated by experimental verification.

Construction of acenaphthylenes via C-H activation-based tandem penta- and hexaannulation reactions.

Acenaphthylene-containing polycyclic aromatic hydrocarbons (AN-PAHs) are noteworthy structural motifs for organic functional materials due to their non-alternant electronic structure, which increases electron affinity. However, the synthesis of AN-PAHs has traditionally required multiple sequential synthetic steps, limiting structural diversity. Herein, we present a tandem C-H penta- and hexaannulation reaction of aryl alkyl ketone with acetylenedicarboxylate. This integrated approach enhances overall efficiency and selectivity, marking a significant advancement in AN-PAH synthesis. Mechanistic studies unveil an orchestrated extension of five- and six-membered rings through C-H activation-annulation and Diels-Alder reaction. Additionally, the tandem annulation reaction can be performed stepwise, further validating the proposed mechanism and increasing the structural diversity of AN-PAHs.

Iridium‐Pyrazolato Complex Catalyzed Dehydrogenative Alkylation of Ketones and Arylacetonitriles with Primary Alcohols

Herein, we report the use of an air‐stable iridium pyrazolato complex as an effective catalyst for the α‐alkylation of ketones and arylacetonitriles with primary alcohols, employing borrowing hydrogen strategy. The alkylation reactions were efficiently conducted at 120 °C in toluene utilizing a very low catalyst loading (0.1 mol%). A broad range of ketones and arylacetonitriles, in combination with various aromatic and aliphatic primary alcohols, were successfully transformed into the corresponding α‐alkylated products. Additionally, quinoline derivatives were synthesized from 2‐aminobenzylalcohol and ketones using dehydrogenative coupling strategy. A mechanistic investigation unveiled that the key step involved alcohol activation via metal‐ligand cooperation.

Enantioselective Alkylation of Ketones In Flow

Enantioselective Alkylation of Ketones In Flow

Catalytic Synthesis of Fluoroalkyl Ketones

Fluoroalkyl ketones are a class of structural motifs which are ubiquitous in bioactive molecules, and serve as synthons for diverse value‐added fluorine‐containing targets. The presence of fluorine significantly alters the lipophilicity and bioactivity of alkyl ketones as well as imposes additional challenges on the synthesis of fluoroalkyl ketones. Traditional methods for the synthesis of fluoroalkyl ketones heavily rely on multiple‐step manipulations which require stoichiometric reagents and suffer from low efficiency. Thus, the development of synthesizing fluoroalkyl ketones enabled by catalytic methods is highly valuable yet challenging. This Concept summarizes the recent renaissance in developing catalytic methods for the synthesis of fluoroalkyl ketones with diverse substitution patterns from different fluorine‐containing precursors. In addition, further efforts for catalytic method development are also discussed

Homologation of Ketones: Direct Transformation of Alkyl Ketones to Aryl Ketones via Photoredox Catalyzed Deacylation-Aroylation Sequence.

Ketones, as essential functional group skeletons, have garnered significant interest due to their diverse transformations. Herein, we describe a versatile photoredox catalyzed deacylation-aroylation strategy that enables the direct transformation of alkyl ketones to aryl ketones. This process involves photoredox deacylation of dihydroquinazolinones derived from alkyl ketones to generate alkyl radicals, followed by subsequent NHC-catalyzed or NHC-mediated radical aroylation.

Formation of C–C and C–N bonds through primary alcohol oxidation catalyzed by ruthenium(II) POCOP pincer complexes

In this study, we present the successful application of new and known stable 16‐electron ruthenium(II) pincer complexes POCOP, based on the naphthoresorcinate backbone, [Ru(X)(POCOP)(CO)] (X = H, Cl, Br, I, OCOCF3), in the catalytic alkylation of ketones and the coupling between amines and primary alcohols under mild conditions. These protocols demonstrated tolerance to a wide range of alcohols, ketones, and anilines, with reactions proceeding in high conversions and selectivity towards the hydrogenated ketones and the imines. The use of an excess of alcohol as the proton source facilitated the formation of the hydrogenated products. These results mark a significant advancement in the development of catalytic reactions with ruthenium POCOP pincer derivatives.

Electrosynthesis of Quinoxalines via Intermolecular Cyclization/Dehydrogenation of Ketones with o-Phenylenediamines

AbstractIn this study, we proposed a novel electrochemical dehydrogenative synthetic method for preparing 2-substituted quinoxalines by intermolecular cyclization of aryl alkyl ketones and o-phenylenediamines. This method gave various quinoxalines in yields ranging from 35% to 71%. This novel protocol employs mild reaction conditions and offers moderate to excellent yields, a wide substrate scope, and broad functional-group compatibility. Furthermore, a late-stage functionalization and the wide substrate scope demonstrated the synthetic utility of this protocol.

Macrocycle‐Based Charge Transfer Cocrystals with Dynamically Reversible Chiral Self‐Sorting Display Chain Length‐Selective Vapochromism to Alkyl Ketones

AbstractChirality‐driven self‐sorting plays an essential role in controlling the biofunction of biosystems, such as the chiral double‐helix structure of DNA from self‐recognition by hydrogen bonding. However, achieving precise control over the chiral self‐sorted structures and their functional properties for the bioinspired supramolecular systems still remains a challenge, not to mention realizing dynamically reversible regulation. Herein, we report an unprecedented saucer[4]arene‐based charge transfer (CT) cocrystal system with dynamically reversible chiral self‐sorting synergistically induced by chiral triangular macrocycle and organic vapors. It displays efficient chain length‐selective vapochromism toward alkyl ketones due to precise modulation of optical properties by vapor‐induced diverse structural transformations. Experimental and theoretical studies reveal that the unique vapochromic behavior is mainly attributed to the formation of homo‐ or heterochiral self‐sorted assemblies with different alkyl ketone guests, which differ dramatically in solid‐state superstructures and CT interactions, thus influencing their optical properties. This work highlights the essential role of chiral self‐sorting in controlling the functional properties of synthetic supramolecular systems, and the rarely seen controllable chiral self‐sorting at the solid‐vapor interface deepens the understanding of efficient vapochromic sensors.

Macrocycle-Based Charge Transfer Cocrystals with Dynamically Reversible Chiral Self-Sorting Display Chain Length-Selective Vapochromism to Alkyl Ketones.

Chirality-driven self-sorting plays an essential role in controlling the biofunction of biosystems, such as the chiral double-helix structure of DNA from self-recognition by hydrogen bonding. However, achieving precise control over the chiral self-sorted structures and their functional properties for the bioinspired supramolecular systems still remains a challenge, not to mention realizing dynamically reversible regulation. Herein, we report an unprecedented saucer[4]arene-based charge transfer (CT) cocrystal system with dynamically reversible chiral self-sorting synergistically induced by chiral triangular macrocycle and organic vapors. It displays efficient chain length-selective vapochromism toward alkyl ketones due to precise modulation of optical properties by vapor-induced diverse structural transformations. Experimental and theoretical studies reveal that the unique vapochromic behavior is mainly attributed to the formation of homo- or heterochiral self-sorted assemblies with different alkyl ketone guests, which differ dramatically in solid-state superstructures and CT interactions, thus influencing their optical properties. This work highlights the essential role of chiral self-sorting in controlling the functional properties of synthetic supramolecular systems, and the rarely seen controllable chiral self-sorting at the solid-vapor interface deepens the understanding of efficient vapochromic sensors.

Development of a plugging material featuring external flexibility and internal rigidity

Recognizing the challenges of low strength, inadequate cementation, significant pore development, and excellent connectivity of reef limestone, as well as the persistent issues of ‘re-leakage’ and increasing leaks when using rigid bridge plugs, this paper posits the use of materials possessing both flexible and rigid properties for the prevention of leaks and plugging in reef limestone formations. Consequently, a plugging material exhibiting external flexibility and internal rigidity is developed (EFIR Material). This synergistic approach employs the deformability of flexible materials and the skeletal support of rigid materials to create a high-strength, dense plugging section. The new design enhances the formation’s pressure-bearing capacity while effectively addressing leakage issues. The material’s functional structure design, a core-shell structure of EFIR, is achieved by reverse-phase suspension polymerization of acrylamide (AM), 2-acrylamide-2-methylpropanesulfonic acid (AMPS), and alkyl ketone polymer (NVP), water-soluble monomers functioning as the shell and modified sand as the core. The results indicate that EFIR retains significant flexibility and strength upon water absorption and expansion. A sand bed made from 10 to 18 mesh calcareous sand exhibits excellent sealing properties. The optimal dosage of 3%-4% produces robust sealing effects, withstands pressures up to 7 MPa, and results in a tightly cemented, high-strength sand bed post-sealing with reef tuff, displaying high-quality sealing that is resistant to re-leakage.

Characterization of 2-Butanone Peroxide Oligomeric Profiles and Their Associated Gas-Phase and Solution-Phase Rearrangement Products by Electrospray Ionization Mass Spectrometry for Forensic Applications.

2-Butanone peroxide (also known as methyl ethyl ketone peroxide, MEKP) has applications as a cross-linker in the chemical industry and is also encountered as a homemade primary high explosive; therefore, it is of interest to both process chemists and forensic examiners. Specifically for forensic applications, we demonstrate that when traditional synthetic procedures, available to any hobbyist, are utilized to generate MEKP, oligomeric peroxide units (n ≤ 12), along with several other oligomeric byproduct distributions, are readily observed by liquid chromatography-mass spectrometry (LC-MS). These oligomeric byproducts correspond to the formation of methyl/ethyl ketone end group(s) at the oligomer end group (i.e., loss of ethanol(s) and/or methanol(s) from the oligomer termini). Based on the interpretation of the MS and MS/MS behavior along with the characterization of newly generated terminal alkyl ketone products, we propose that these byproducts are consistent with a Hock-like rearrangement of the primary MEKP distribution in the acidified reaction medium. Following a procedure for homemade preparation, triplicate lots were synthesized. Unique oligomeric and byproduct distributions provided discriminatory power between the synthetic lots. Furthermore, the distributions of MEKP oligomers and the various byproducts in the initiated MEKP match the intensity distributions observed in the intact material with remarkable accuracy. This observation suggests that the postinitiation residue of MEKP could be associated or dissociated from a separately collected intact material obtained during an investigation by examining these oligomeric and byproduct profiles.

Toxicological and Sedative Effects of Chipilin (Crotalaria longirostrata) Leaf Extracts Obtained by Maceration and Supercritical Fluid Extraction.

Chipilin (Crotalaria longirostrata) is consumed as a vegetable in the preparation of traditional dishes. As a folk medicine, Chipilin extracts are used as a hypnotic and sedative agent; however, there are few reports that support these uses. This study aimed to characterize the compounds present in Chipilin leaf extracts and to investigate their sedative effect using zebrafish as an in vivo model. Extracts were obtained by maceration with water (H2O), ethanol (EtOH), and EtOH-H2O, while oleoresin was obtained by supercritical fluid extraction (SFE). Total phenolic and flavonoid contents were quantified by colorimetric methods. Phytochemical constituents were identified by gas chromatography-mass spectrometry (GC-MS) analysis. The chronic and acute toxicities of Chipilin extracts were tested in zebrafish embryos and larvae, respectively. Chipilin sedative effect was tested by the larvae response to dark-light-dark transitions. EtOH-H2O extracts had the highest value of total phenolics (5345 ± 5.1 μg GAE/g), followed by water and oleoresin (1815 ± 5.1 and 394 ± 5.1 μg GAE/g, respectively). In water extracts were identified the alkaloid trachelanthamidine, 1,2β-epoxy- and the alkyl ketone 7,9-di-tert-butyl-1-oxaspiro(4,5)deca-6,9-diene-2,8-dione, while oleamide, α-monostearin, and erucamide were detected in all samples except in water extracts. Oleoresin extract had the lowest embryotoxicity (LC50 = 4.99 μg/mL) and the highest sedative effects. SFE is a green alternative to obtain Chipilin extracts rich in erucamide, an endocannabinoid analogue, which plays an important role in the development of the central nervous system and in modulating neurotransmitter release.

Access to Functionalized Cyclohex-2-enones from a Multicomponent Cascade Reaction of Readily Available Alkynes, Ketones, and Ethyl Acetoacetate.

The synthesis of cyclohex-2-enone derivatives is a topic of current interest in organic chemistry. A novel three-component cascade reaction of alkynes with ketones and ethyl acetoacetate has been uncovered. This process provides di- and trisubstituted cyclohex-2-enones in good yields with excellent functional group tolerance. A variety of terminal alkynes and a wide range of aryl, alkyl, and cyclic ketones are viable in this transformation. Successful scale-up preparation and synthetic transformations have demonstrated the potential of this simple operating protocol.

Zn(II)‐Stabilized Azo‐Anion Radical Catalyzed Sustainable C−C Bond Formation: Regioselective Alkylation of Fluorene, Oxindole, and Indoles

AbstractHerein we report a sustainable approach for the alkylation of ketones, 9H‐fluorene, oxindole, and indole using alcohols as the alkylating agent catalyzed by a well‐defined air‐stable zinc catalyst (1 a) of a tridentate redox non‐innocent arylazo ligand, 2‐((4‐chlorophenyl)diazenyl)‐1,10‐phenanthroline (La). 2–3 mol % of 1 a efficiently produces substituted α‐alkylated ketones, 9‐alkylated fluorenes, C3‐alkylated oxindoles, and C3‐alkylated indoles in moderate to good isolated yields. In aerial condition, the formation of bis(indolyl)methane (BIMs) derivatives were observed when indoles were subjected to alkylation by primary alcohols. A few drug molecules containing BIMs were prepared in good isolated yields. The catalyst 1 a exhibited good chemoselectivity during the functionalization of fluorene and indole with oleyl alcohol and β‐citronellol. A few control experiments, including deuterium labeling experiments, performed to unveil the reaction mechanism indicate that the one‐electron reduced azo‐anion radical species [1 a]‐formed in situ, acts as the active catalyst. All the redox events occur at the redox‐active aryl‐azo ligand, which acts as the reservoir of hydrogen and electrons throughout the catalytic cycle, keeping the Zn(II)‐center as a template.

DFT study on the Stereoselectivity of Asymmetric Synthesis of C, N‐Cyclic Azomethine Imines with Allyl Alkyl Ketones

AbstractBased on the density functional theory, the stereoselectivity of the asymmetric synthesis of tetrahydroisoquinolinopyrazole derivatives by the cycloaddition reaction of C, N‐cyclic azomethine imines with allyl alkyl ketones which was catalyzed using a chiral primary amine is studied theoretically. The results demonstrate that the four chiral transition states (TS‐1R2R, TS‐1R2S, TS‐1S2R and TS‐1S2S) are formed by the reaction of dienamine intermediate with C, N‐cyclic azomethine imine, and the reaction barrier of TS‐1R2S is in the lowest level (ΔG=6.98 kcal/mol). The consequence reveal that the 1R2S configuration product is formed by TS‐1R2S transition state. Non‐covalent interaction and electron density topology analysis show that the stereoselectivity of the chiral product is determined through van der Waals forces and hydrogen bond interaction of the transition state molecules.

Inside Cover Picture

Functionalization of unactivated sp3 C—H bonds of cyclic and linear alkanes to high‐value‐added chemicals is one of the most important classes of chemical transformations and has high synthetic potential in synthetic chemistry. A metal‐free, green, and sustainable functionalization of unactivated alkyl sp3 C—H bonds is reported using iodine(III) as a feasible dehydrogenation agent under visible light or KBr, and alkyl chlorides, bromides, alcohols, and ketones could be constructed by addition of different coupling reagents. More details are discussed in the article by Zhai et al. on page 505—510.image