Symmetrical Ketones Research Articles

An Electrocatalytic Cascade Reaction for the Synthesis of Ketones Using CO2 as a CO Surrogate

AbstractThe construction of carbonyl compounds via carbonylation reactions using safe CO sources remains a long‐standing challenge to synthetic chemists. Herein, we propose a catalyst cascade Scheme in which CO2 is used as a CO surrogate in the carbonylation of benzyl chlorides. Our approach is based on the cooperation between two coexisting catalytic cycles: the CO2‐to‐CO electroreduction cycle promoted by [Fe(TPP)Cl] (TPP=meso‐tetraphenylporphyrin) and an electrochemical carbonylation cycle catalyzed by [Ni(bpy)Br2] (2,2′‐bipyridine). As a proof of concept, this protocol allows for the synthesis of symmetric ketones from good to excellent yields in an undivided cell with non‐sacrificial electrodes. The reaction can be directly scaled up to gram‐scale and operates effectively at a CO2 concentration of 10 %, demonstrating its robustness. Our mechanistic studies based on cyclic voltammetry, IR spectroelectrochemistry and Density Functional Theory calculations suggest a synergistic effect between the two catalysts. The CO produced from CO2 reduction is key in the formation of the [Ni(bpy)(CO)2], which is proposed as the catalytic intermediate responsible for the C−C bond formation in the carbonylation steps.

An Electrocatalytic Cascade Reaction for the Synthesis of Ketones Using CO2 as a CO Surrogate.

The construction of carbonyl compounds via carbonylation reactions using safe CO sources remains a long-standing challenge to synthetic chemists. Herein, we propose a catalyst cascade Scheme in which CO2 is used as a CO surrogate in the carbonylation of benzyl chlorides. Our approach is based on the cooperation between two coexisting catalytic cycles: the CO2-to-CO electroreduction cycle promoted by [Fe(TPP)Cl] (TPP=meso-tetraphenylporphyrin) and an electrochemical carbonylation cycle catalyzed by [Ni(bpy)Br2] (2,2'-bipyridine). As a proof of concept, this protocol allows for the synthesis of symmetric ketones from good to excellent yields in an undivided cell with non-sacrificial electrodes. The reaction can be directly scaled up to gram-scale and operates effectively at a CO2 concentration of 10 %, demonstrating its robustness. Our mechanistic studies based on cyclic voltammetry, IR spectroelectrochemistry and Density Functional Theory calculations suggest a synergistic effect between the two catalysts. The CO produced from CO2 reduction is key in the formation of the [Ni(bpy)(CO)2], which is proposed as the catalytic intermediate responsible for the C-C bond formation in the carbonylation steps.

Potential suppression of multidrug-resistance-associated protein 1 by coumarin derivatives: an insight from molecular docking and MD simulation studies

Human MRP1 protein plays a vital role in cancer multidrug resistance. Coumarins show promising pharmacological properties. Virtual screening, ADMET, molecular docking and molecular dynamics (MD) simulations were utilized as pharmacoinformatic tools to identify potential MRP1 inhibitors among coumarin derivatives. Using in silico ADMET, 50 hits were further investigated for their selectivity toward the nucleotide-binding domains (NBDs) of MRP1 using molecular docking. Accordingly, coumarin, its symmetrical ketone derivative Lig. No. 4, and Reversan were candidates for focused docking study with the NBDs domains compared with ATP. The result indicates that Lig. No. 4, with the best binding score, interacts with NBDs via hydrogen bonds with residues: GLN713, LYS684, GLY683, CYS682 in NBD1, and GLY1432, GLY771, SER769 and GLN1374 in NBD2, which mostly overlap with ATP binding residues. Moreover, doxorubicin (Doxo) was docked to the transmembrane domains (TMDs) active site of MRP1. Doxo interaction with TMDs was subjected to MD simulation in the NBDs free and occupied with Lig. No. 4 states. The results showed that Doxo interacts more strongly with TMD residues in inward facing feature of TMDs helices. However, when Lig. No. 4 exists in NBDs, Doxo interactions are different, and TMD helices show more outward-facing conformation. This result may suggest a partial competitive inhibition mechanism for the Lig. No. 4 on MRP1 compared with ATP. So, it may inhibit active complex formation by interfering with ATP entrance to NBDs and locking MRP1 conformation in outward-facing mode. This study suggests a valuable coumarin derivative that can be further investigated for potent MRP1 inhibitors. Communicated by Ramaswamy H. Sarma

Chiral α-Stereogenic Oxetanols and Azetidinols via Alcohol-Mediated Reductive Coupling of Allylic Acetates: Enantiotopic π-Facial Selection in Symmetric Ketone Addition.

Iridium-tol-BINAP-catalyzed reductive coupling of allylic acetates with oxetanones and azetidinones mediated by 2-propanol provides chiral α-stereogenic oxetanols and azetidinols. As illustrated in 50 examples, complex, nitrogen-rich substituents that incorporate the top 10 N-heterocycles found in FDA-approved drugs are tolerated. In addition to 2-propanol-mediated reductive couplings, oxetanols and azetidinols may serve dually as reductant and ketone proelectrophiles in redox-neutral C-C couplings via hydrogen auto-transfer, as demonstrated by the conversion of dihydro-1a and dihydro-1b to adducts 3a and 4a, respectively. The present method delivers hitherto inaccessible chiral oxetanols and azetidinols, which are important bioisosteres.

Enantioselective Iridium‐Catalyzed Reductive Coupling of Dienes with Oxetanones and N‐Acyl‐Azetidinones Mediated by 2‐Propanol

AbstractCyclometallated iridium‐PhanePhos complexes generated in situ from [Ir(cod)Cl]2 and (R)‐PhanePhos catalyze 2‐propanol‐mediated reductive couplings of 2‐substituted dienes with oxetanone and N‐acyl‐azetidinones to form branched homoallylic oxetanols and azetidinols with excellent control of regio‐ and enantioselectivity without C−C cleavage of the strained ring via enantiotopic π‐facial selection of transient allyliridium nucleophiles. This work represents the first systematic study of enantioselective additions to symmetric ketones.

Enantioselective Iridium-Catalyzed Reductive Coupling of Dienes with Oxetanones and N-Acyl-Azetidinones Mediated by 2-Propanol.

Cyclometallated iridium-PhanePhos complexes generated in situ from [Ir(cod)Cl]2 and (R)-PhanePhos catalyze 2-propanol-mediated reductive couplings of 2-substituted dienes with oxetanone and N-acyl-azetidinones to form branched homoallylic oxetanols and azetidinols with excellent control of regio- and enantioselectivity without C-C cleavage of the strained ring via enantiotopic π-facial selection of transient allyliridium nucleophiles. This work represents the first systematic study of enantioselective additions to symmetric ketones.

Mechanochemical Grignard Reactions with Gaseous CO2 and Sodium Methyl Carbonate.

A one‐pot, three‐step protocol for the preparation of Grignard reagents from organobromides in a ball mill and their subsequent reactions with gaseous carbon dioxide (CO2) or sodium methyl carbonate providing aryl and alkyl carboxylic acids in up to 82 % yield is reported. Noteworthy are the short reaction times and the significantly reduced solvent amounts [2.0 equiv. for liquid assisted grinding (LAG) conditions]. Unexpectedly, aryl bromides with methoxy substituents lead to symmetric ketones as major products.

Mechanochemical Grignard Reactions with Gaseous CO2 and Sodium Methyl Carbonate**

AbstractA one‐pot, three‐step protocol for the preparation of Grignard reagents from organobromides in a ball mill and their subsequent reactions with gaseous carbon dioxide (CO2) or sodium methyl carbonate providing aryl and alkyl carboxylic acids in up to 82 % yield is reported. Noteworthy are the short reaction times and the significantly reduced solvent amounts [2.0 equiv. for liquid assisted grinding (LAG) conditions]. Unexpectedly, aryl bromides with methoxy substituents lead to symmetric ketones as major products.

Fast Addition of s-Block Organometallic Reagents to CO2 -Derived Cyclic Carbonates at Room Temperature, Under Air, and in 2-Methyltetrahydrofuran.

Fast addition of highly polar organometallic reagents (RMgX/RLi) to cyclic carbonates (derived from CO2 as a sustainable C1 synthon) has been studied in 2-methyltetrahydrofuran as a green reaction medium or in the absence of external volatile organic solvents, at room temperature, and in the presence of air/moisture. These reaction conditions are generally forbidden with these highly reactive main-group organometallic compounds. The correct stoichiometry and nature of the polar organometallic alkylating or arylating reagent allows straightforward synthesis of: highly substituted tertiary alcohols, β-hydroxy esters, or symmetric ketones, working always under air and at room temperature. Finally, an unprecedented one-pot/two-step hybrid protocol is developed through combination of an Al-catalyzed cycloaddition of CO2 and propylene oxide with the concomitant fast addition of RLi reagents to the in situ and transiently formed cyclic carbonate, thus allowing indirect conversion of CO2 into the desired highly substituted tertiary alcohols without need for isolation or purification of any reaction intermediates.

Thermal decomposition of Yttrium 2-methylbutyrate in argon

The thermal decomposition of yttrium 2-methylbutyrate (Y(C4H9CO2)3) under argon gas flow has been investigated by means of simultaneous thermogravimetry and differential thermal analysis, FTIR-spectroscopy (solid residue and evolved gas analysis), mass spectrometry, hot-stage optical microscopy and X-ray diffraction with a standard laboratory Cu-tube source as well as with a high-energy synchrotron radiation source. At least one structural transition occurs in the solid state between 100 °C and 160 °C. The decomposition of the Y 2-methylbutyrate salt takes place above 400 °C. A first stage results in the formation of Y2O2CO3 between 400 °C and 490 °C. This decomposition step is accompanied by the release of CO2, a symmetrical ketone (3,5-dimethyl-4-heptanone), as well as probably a terminal alkyne, which could not be unambiguously identified. At higher temperature, Y2O2CO3 is slowly converted to Y2O3 with release of CO2, while some carbonaceous residue is eliminated via combustion. The TG trace reaches the final plateau at about 1200 °C.

Catalytic Pyrolysis of Aliphatic Carboxylic Acids into Symmetric Ketones over Ceria-Based Catalysts: Kinetics, Isotope Effect and Mechanism

Ketonization is a promising way for upgrading bio-derived carboxylic acids from pyrolysis bio-oils, waste oils, and fats to produce high value-added chemicals and biofuels. Therefore, an understanding of its mechanism can help to carry out the catalytic pyrolysis of biomass more efficiently. Here we show that temperature-programmed desorption mass spectrometry (TPD-MS) together with linear free energy relationships (LFERs) can be used to identify catalytic pyrolysis mechanisms. We report the kinetics of the catalytic pyrolysis of deuterated acetic acid and a reaction series of linear and branched fatty acids into symmetric ketones on the surfaces of ceria-based oxides. A structure–reactivity correlation between Taft’s steric substituent constants Es* and activation energies of ketonization indicates that this reaction is the sterically controlled reaction. Surface D3-n-acetates transform into deuterated acetone isotopomers with different yield, rate, E≠, and deuterium kinetic isotope effect (DKIE). The obtained values of inverse DKIE together with the structure–reactivity correlation support a concerted mechanism over ceria-based catalysts. These results demonstrate that analysis of Taft’s correlations and using simple equation for estimation of DKIE from TPD-MS data are promising approaches for the study of catalytic pyrolysis mechanisms on a semi-quantitative level.

Equilibrium in the Catalytic Condensation of Carboxylic Acids with Methyl Ketones to 1,3-Diketones and the Origin of the Reketonization Effect.

Acetone is the expected ketone product of an acetic acid decarboxylative ketonization reaction with metal oxide catalysts used in the industrial production of ketones and for biofuel upgrade. Decarboxylative cross-ketonization of a mixture of acetic and isobutyric acids yields highly valued unsymmetrical methyl isopropyl ketone (MIPK) along with two less valuable symmetrical ketones, acetone and diisopropyl ketone (DIPK). We describe a side reaction of isobutyric acid with acetone yielding the cross-ketone MIPK with monoclinic zirconia and anatase titania catalysts in the absence of acetic acid. We call it a reketonization reaction because acetone is deconstructed and used for the construction of MIPK. Isotopic labeling of the isobutyric acid’s carboxyl group shows that it is the exclusive supplier of the carbonyl group of MIPK, while acetone provides only methyl group for MIPK construction. More branched ketones, MIPK or DIPK, are less reactive in their reketonization with carboxylic acids. The proposed mechanism of reketonization supported by density functional theory (DFT) computations starts with acetone enolization and proceeds via its condensation with surface isobutyrate to a β-diketone similar to β-keto acid formation in the decarboxylative ketonization of acids. Decomposition of unsymmetrical β-diketones with water (or methanol) by the retrocondensation reaction under the same conditions over metal oxides yields two pairs of ketones and acids (or esters in the case of methanol) and proceeds much faster compared to their formation. The major direction yields thermodynamically more stable products—more substituted ketones. DFT calculations predict even a larger fraction of the thermodynamically preferred pair of products. The difference is explained by some degree of a kinetic control in the opposite direction. Reketonization has lower reaction rates compared to regular ketonization. Still, a high extent of reketonization occurs unnoticeably during the decarboxylative ketonization of acetic acid as the result of the acetone reaction with acetic acid. This degenerate reaction is the major cause of the inhibition by acetone of its own rate of formation from acetic acid at high conversions.

Radical and oxidative pathways in the pyrolysis of a barium propionate-acetate salt

Film and powder samples from a BaAc2 solution in propionic acid/MeOH were decomposed in different atmospheres and their thermal decomposition was characterized by means of thermogravimetry coupled with evolved gas analysis techniques (TG-FTIR, EGA-MS) and chemical and structural methods (EA, XRD, FTIR). The thermal behavior of the films was found to be different than the corresponding powder, in terms of volatiles, kinetics, intermediate phases and purity of final product. The mixed Ba-Prop-Ac salt obtained from solution decomposes to BaCO3 before 400 °C through oxidative degradation, and above 400 °C in inert atmosphere through a radical path releasing symmetrical ketones. Its double melting behavior is also highlighted and its decomposition understood by comparison with BaProp2 and BaAc2 precursors, and put into the context of YBa2Cu3O7-∂ (YBCO) film pyrolysis.

Sodium Methyl Carbonate as an Effective C1 Synthon. Synthesis of Carboxylic Acids, Benzophenones, and Unsymmetrical Ketones

Reported is the synthesis of carboxylic acids, symmetrical ketones, and unsymmetrical ketones with selectivity achieved by exploiting the differential reactivity of sodium methyl carbonate with Grignard and organolithium reagents.

The Carbonylation of Phenylcopper Tri-n -Butylphosphine Complex [PhCu.P(n-Butyl)3] Produces the Symmetrical Ketone Benzophenone

The Carbonylation of Phenylcopper Tri-n -Butylphosphine Complex [PhCu.P(n-Butyl)3] Produces the Symmetrical Ketone Benzophenone Jennifer A. Ebert, Greg W. Ebert Abstract In 1972 Jeffrey Schwartz of Massachusetts Institute of Technology published a seminal paper on the reaction of carbon monoxide with alkylcopper complexes to form symmetrical ketones (Schwartz, 1972). This was one of the earliest examples of the carbonylation of an organocopper reagent and gave a tantalizing glimpse into the possibility of forming copper acyl anion complexes. While that work examines alkylcopper reagents in some detail, no mention is made concerning the study of aromatic copper reagents. We were interested in exploring whether or not a similar approach could be used to carbonylate and convert arylcopper reagents into symmetrical aryl ketones thereby opening up this reaction to aromatic organocopper compounds. We now wish to report the successful carbonylation of phenylcopper tri-n-butylphosphine complex [PhCu.P(n-butyl)3] to produce the symmetrical ketone benzophenone: PhCu.P(n-butyl)3 + CO → Ph-C(O)-Ph Full Text: PDF DOI: 10.15640/jcb.v7n2a2

Acetocatechol functionalized viologen as polyfunctional material that responds to anion, cation and reductant in aqueous and organic solvents

Both viologen and catechol have been studied extensively. However, the stability of catechol-Fe(III) without additional oxidant is still not well understood. In this paper, we introduced acetocatechol into viologen to investigate its interactions with anion, cation, and reductant, as well as the stability of its Fe(III) complexes. This acetocatechol functionalized viologen, 1,1′-bis(2-(3,4-dihydroxyphenyl)-2-oxoethyl)- [4,4′-bipyridine]-1,1′-diium chloride (H6V·Cl2) exists in central symmetric ketone cation form in solid state. Viologen cation increased the acidity of the aceto group and deprotonated the enolic proton to form monodeprotonated enolic H5V+ in the presence of anion/base, which had the deepest color in organic solvents. The absorbance maximum of H5V+ increased with the decrease of solvent polarity. It also interacted with B4O72− and MoO42− by forming catechol ester in DMSO solution. The catechol moiety can coordinate to metal ion, especially Fe(III), in both aqueous and DMSO solution. In particular, it coordinated to Fe(III) much more readily in aqueous solution than in DMSO. Green monocatecholato Fe(III) and red-brown bis-catecholato Fe(III) complex also formed in aqueous solution. The monocatecholato Fe(III) complex first-order dimerized in aqueous solution at room temperature but underwent second-order decomposition to Fe(II) complex at 60 °C. The biscatecholato Fe(III) complex also transferred to other Fe(III) complexes at first- and second-order at room-temperature and 60 °C respectively. The t1/2 varied from several hours at room-temperature and several minutes at 60 °C at 10−4 M concentration. The interactions of Fe(III) in DMSO is much more complex than that of acetocatecholate without viologen. Fe(III) can also be reduced to free viologen radicals in the presence of sodium Na2S2O4, but not N2H4. In conclusion, this polyfunctional compound responds to anion via aceto and catechol, metal ion via catechol hydroxyl, while reductant via viologen.

Hydroboration-Oxidation of (±)-(1α,3α,3aβ,6aβ)-1,2,3,3a,4,6a-Hexahydro-1,3-pentalenedimethanol and Its O-Protected Derivatives: Synthesis of New Compounds Useful for Obtaining (iso)Carbacyclin Analogues and X-ray Analysis of the Products.

Hydroboration-oxidation of 2α,4α-dimethanol-1β,5β-bicyclo[3.3.0]oct-6-en dibenzoate (1) gave alcohols 2 (symmetric) and 3 (unsymmetric) in ~60% yield, together with the monobenzoate diol 4a (37%), resulting from the reduction of the closer benzoate by the intermediate alkylborane. The corresponding alkene and dialdehyde gave only the triols 8 and 9 in ~1:1 ratio. By increasing the reaction time and the temperature, the isomerization of alkylboranes favours the un-symmetrical triol 9. The PDC oxidation of the alcohols gave cleanly the corresponding ketones 5 and 6 and the deprotection of the benzoate groups gave the symmetrical ketone 14, and the cyclic hemiketal 15, all in high yields. The ethylene ketals of the symmetrical ketones 11 and 13 were also obtained. The compounds 5, 6, 11, 13, 14 could be used for synthesis of new (iso)carbacyclin analogues. The structure of the compounds was established by NMR spectroscopy and confirmed by X-ray crystallography.

Bimolecular condensation reactions of butan-1-ol on Ag–CeO2 decorated multiwalled carbon nanotubes

CeO2/MWCNTs, Ag/MWCNTs and Ag–CeO2/MWCNTs hybrid composite nanomaterials with 5 wt% active component contents applied as catalysts of dehydrogenation and consecutive bimolecular condensation of a primary alcohol, butan-1-ol, revealed diversified properties. CeO2/MWCNTs showed the catalytic activity of pure cerium oxide despite its much lower content. Products obtained over Ag/MWCNTs did not contain ketone or ester in spite of higher dehydrogenation. Ag–CeO2/MWCNTs showed superior catalytic activity and selectivity towards subsequent C–C coupling, thus significantly higher yield of the symmetrical ketone (heptan-4-one) was achieved (at 400 °C, yield of the ketone over CeO2/MWCNTs and over Ag–CeO2/MWCNTs were 1 and 28%, respectively). The preserved character of the transformations over the CeO2/MWCNTs was shifted by tens of degrees to lower temperatures. It clearly indicates a synergistic interaction between the components.

Thermal behavior and decomposition of cerium(III) butanoate, pentanoate and hexanoate salts upon heating in argon

The thermal behavior and decomposition of Ce-butanoate monohydrate (Ce(C3H7CO2)3·H2O), Ce-pentanoate (Ce(C4H9CO2)3) and Ce-hexanoate (Ce(C5H11CO2)3) were studied in a flow of argon while heating at 5°C/min. By means of several techniques such as simultaneous TG-DTA, FTIR evolved gas analysis, in-situ x-ray diffraction using a synchrotron source and hot-stage microscopy, it was found that all three compounds undergo melting transitions prior to decomposition and that decomposition involves intermediate stages including at least a Ce2O(CnH2n+1CO2)4 intermediate (n=3, 4 or 5 for Ce-butanoate, pentanoate or hexanoate respectively). The final decomposition product consists of CeO2, which is formed through a Ce-oxycarbonate. The Ce3+→Ce4+ oxidation seems to proceed via Ce2O3 that first results from the decomposition of the oxycarbonate phase. During the whole decomposition process, the evolved gas species consist of CO2 and symmetrical ketones.

Capitalizing on Protecting Groups to Influence Vinyl Catechol Monomer Reactivity and Monomer Gradient in Carbanionic Copolymerization

Several vinyl catechol‐based monomers with systematically varied acetal protecting groups suitable for carbanionic polymerization are introduced. All monomers are based on the 4‐vinyl benzodioxole or 5‐vinyl benzodioxole structure and differ in the nature of the protecting group for the catechol functionalities. Different symmetric ketones are used for the protection of the diol functionality. Polymers with average molecular weight from 2500 to 25 000 g mol−1 (Mw/Mn < 1.15) are obtained from homopolymerization of the protected monomers. All monomers are examined regarding the influence of the protecting group on the copolymerization behavior with styrene, using in situ 1H NMR kinetic studies. Length and structure of the alkyl chains generally show no influence for all monomers based on 5‐vinyl benzodioxole. In contrast, all monomers with the protecting group in direct vicinity to the propagating vinyl moiety exhibit dependence between monomer reactivity and chain length of the protecting group. A decrease of the monomer reactivity enables control of the gradient in the copolymerization with styrene. Finally, the first terpolymerization kinetics of a carbanionic polymerization in 1H NMR kinetics is presented, combining the monomers 3‐vinyl catechol acetonide, styrene, and 4‐vinyl catechol acetonide, which enables the one‐pot synthesis of double gradient terpolymers. image