Ketone Functional Groups Research Articles

Carbonyl-Directed Aliphatic Fluorination: A Special Type of Hydrogen Atom Transfer Beats Out Norrish II.

Recently, our group reported that enone and ketone functional groups, upon photoexcitation, can direct site-selective sp3 C-H fluorination in terpenoid derivatives. How this transformation actually occurred remained mysterious, as a significant number of mechanistic possibilities came to mind. Herein, we report a comprehensive study describing the reaction mechanism through kinetic studies, isotope-labeling experiments, 19F NMR, electrochemical studies, synthetic probes, and computational experiments. To our surprise, the mechanism suggests intermolecular hydrogen atom transfer (HAT) chemistry is at play, rather than classical Norrish hydrogen atom abstraction as initially conceived. What is more, we discovered a unique role for photopromoters such as benzil and related compounds that necessitates their chemical transformation through fluorination in order to be effective. Our findings provide documentation of an unusual form of directed HAT and are of crucial importance for defining the necessary parameters for the development of future methods.

Upgrading ketone synthesis direct from carboxylic acids and organohalides

The ketone functional group has a unique reactivity in organic chemistry and is associated with a number of useful reactions. Catalytic methods for ketone synthesis are continually being developed. Here, we report a photoredox, nickel and phosphoranyl radical synergistic cross-electrophile coupling of commercially available chemicals, aromatic acids and aryl/alkyl bromides. This allows for concise synthesis of highly functionalized ketones directly, without the preparation of activated carbonyl intermediates or organometallic compounds, and thus complements the conventional Weinreb ketone synthesis. Use of the appropriate photocatalyst, ligand amount and solvents can match the reaction rate required by any simple catalytic cycle. The practicality and synthetic robustness of the reaction are illustrated by the facile synthesis of complex ketones from readily available feedstock chemicals.

Comparison of the Oil Composition of Clarias gariepinus Collected from Four Lagoons in Lagos, South Western Nigeria

Oil composition of Clarias gariepinus collected from various locations were studied and compared. Oils contained in the fishes were extracted using Soxhlet extraction method. The physiochemical properties of the oils were determined using official methods of analysis while the fatty acid composition was analysed using Gas Chromatography- Mass Spectrophotometer. The functional groups present in the oils were also detected using Fourier Transform Infra-red Spectroscopy (FTIR). The oil content for the fishes was in the range of 30.65%-40.57%. The oil extracted from C. gariepinus collected from Badagry lagoon had the highest peroxide and iodine values (5.12 mg KOH/g and 129 mgI2/100 g). The fatty acid composition shows that the oils contains large number of essential polyunsaturated fatty acids except for the oil extracted from C. gariepinus collected from Ikorodu lagoon that contains large number of monounsaturated fatty acids. The FTIR spectra show the presence of carboxylic acid, methylene, esters, ketone and alcohol functional group. It was deduced from this study that habitat had strong impact on the oil composition of C. gariepinus.

4-(4-Meth-oxy-phen-yl)-8-oxo-3-(phenyl-selan-yl)spiro-[4.5]deca-3,6,9-trien-2-yl]methyl-cyanamide.

The title compound, C25H22N2O2Se, crystallizes in the space group P21/c with one mol-ecule in the asymmetric unit. The compound was synthesized by the addition of phenyl-selenyl bromide to a cyanamide. The phenyl-selenyl portion and the cyano group, as well as the ketone functional group in the cyclo-hexa-2,5-dien-1-one portion of the structure, are disordered, with occupancy factors of 0.555 (14) and 0.445 (14).

Se(CH2C(O)CH3)3][B12F11NH3]: The first selenium cation with three β-ketone substituents.

The reaction of [Se8][B12F11NH3]2 with acetone and subsequent crystallization from acetone/diethyl ether yielded the selenium cation [Se(CH2C(O)CH3)3]+ as a by-product, which is stabilized by the weakly coordinating undeca-fluorinated anion [B12F11NH3]-. While attempting to crystallize pure [Se8][B12F11NH3]2, the structure of the isolated product, namely, tris-(2-oxoprop-yl)selenium 1-ammonio-undeca-fluoro-dodeca-borate, was surprising. The cation [Se(CH2C(O)CH3)3]+ represents the first example for a cationic selenium compound with three ketone functional groups located in the β-position with respect to the selenium atom. The cation possesses almost trigonal-pyramidal C 3 symmetry and forms hydrogen bonds to the ammonio group of the anion.

Asymmetric Synthesis of the Tricyclooctane Core of Trachylobane Natural Products and Related Terpenoids.

Enantioselective synthesis of a highly versatile building block en route to trachylobanes and related terpenoids is presented. The synthesis features diastereoselective Diels-Alder cycloaddition reaction, a cyclopropanation/homoquadricyclane rearrangement cascade, and palladium-catalyzed C-H acetoxylation. The targeted tricyclooctane was obtained in 20% yield over 8 steps and in 95% ee. The ketone and alcohol functional groups serve as handles for further elaboration.

Significance of the High Abundance of Pentacyclic Triterpenyl and Hopenyl Acetates in Sphagnum Peat Bogs from Northern Spain

Global warming is expected to increase the rate of CH4 emission from acidic peatlands leading to an increased interest on its mechanisms of formation. The main routes are through the reduction of CO2 by molecular hydrogen and through the cleavage of acetate. A predominance of the former, a reaction which also competes with homoacetogenesis to form acetate, may enrich the media in acetate, which could potentially be incorporated in the peat molecular markers. Acetates of triterpenoid biomarkers have been identified in peats and lake sediments and related to the input of higher plants. Nevertheless, the acetyl derivatives are found in very low amounts in fresh plants and in much lower amount than other derivatives with alcohol or ketone functional groups. The dichloromethane/methanol extracts of Asturian peat bog profiles (North Spain) were analyzed using gas chromatography/mass spectrometry (GC/MS) and compound-specific-isotope-analysis (CSIA). They show abundance of acetates of compounds with oleanane, ursane, and lupane skeletons derived from higher plants and with hopane skeleton, which can be considered a characteristic of these peats. Two families of 3-oxyhopenyl acetates with -17(21)- and -22(29)- configurations were detected in the upper part of the peat profiles, having a δ13C isotopic composition enriched by 4‰ compared with that of higher plant triterpenoids, and similar to that of microorganism-derived regular hopanoids. Both the acetate and ketone derivatives with the oxygenated functionality at C-3 were generally present in a given extract and tended to accumulate at certain depth in the profiles and in specific levels. The widespread occurrence of acetyl-derivatives, their higher concentration in the deeper layers of the peat, the fact that the acetates correspond to different compound families of diverse source and the very low amount of acetates identified in Ericaceae-contributing to the peat compared to the alcohols suggest that they were formed in the peat under particularly favorable environmental conditions. We postulate that these conditions could have been the existence of a medium enriched in acetic acid produced by the dominance of hydrogenotrophic methanogenesis and/or homoacetogenesis over acetoclastic methanogenesis. This phenomenon that has been preferentially described in Sphagnum bogs at high latitudes, and in the deeper layers of peat, appears to be also present in the temperate peats of the Asturian coast.

Development of a CDC-certified total testosterone assay for adult and pediatric samples using LC–MS/MS

BackgroundHighly accurate and sensitive method to measure testosterone in hypogonadal male, female and children is vital for proper diagnosis of hormone-related conditions and their treatment. ObjectiveTo develop an accurate and robust total testosterone ESI-LC-MS/MS quantification method with a simple sample preparation workflow and sufficient sensitivity for serum or plasma samples of all gender and age groups, via ketone functional group derivatization (using Amplifex™ Keto Reagent). MethodA simple sample preparation method to accommodate both low and high numbers of samples was developed using simultaneous protein precipitation and derivatization with Amplifex™ Keto reagent, followed by centrifugation and direct injection of supernatant into an LC-MS/MS system (SCIEX Topaz™ IVD LC-MS/MS, in which MS is equivalent to a SCIEX 4500MD Mass Spectrometer). Total testosterone in human serum or plasma samples was quantified using an external calibration curve generated by calibrators spanning a broad concentration range of ∼1–2000 ng/dL (10–20,000 pg/mL), traceable to NIST 971 SRM. 13C3-enriched testosterone was used as an internal standard to correct for both analyte loss during sample preparation and matrix effect during analysis (Supplementary Information: SI Fig. 4C). Two methods, one using a 96-well filter plate and another using Eppendorf tubes, were developed. Both methods were certified by the Centers for Disease Control (CDC) hormone standardization (HoSt) program for total serum testosterone. The feasibility of implementing the method for plasma and serum samples was tested via a small-scale method comparison study between matched pediatric serum and plasma samples derived from the same donor. In addition, plasma samples originating from the same donor collected in two different anticoagulant tube types (Li-heparin and K2EDTA) were compared. ResultsUsing in-house formulated NIST 971-traceable calibrators, the method was linear (r2 > 0.999) between 1 and 2000 ng/dL (10 and 20,000 pg/mL) with a limit of detection of approximately 1 ng/dL (10 pg/mL). The testosterone concentration bias against 40 reference samples from the HoSt certification program was absolute <3% with an average %CV of ∼3–4%. More than 78% of samples passed the CDC bias criterion of ±6.4%. Comparison between pediatric matched serum and plasma samples resulted in high correlation (r2 = 0.997) and bias of <5%. The calculated % difference between matched adult serum and plasma samples was ∼1%. ConclusionsFeasibility for an accurate and streamlined method suitable for measuring total testosterone in all human samples was demonstrated with a choice of sample preparation workflow to suit low or high number of samples. The method can potentially be used for plasma matrix from different blood collection tubes (Li-Heparin and K2EDTA).

Elucidating Peptidoglycan Structure: An Analytical Toolset.

Peptidoglycan (PG) is a ubiquitous structural polysaccharide of the bacterial cell wall, essential in preserving cell integrity by withstanding turgor pressure. Any change that affects its biosynthesis or degradation will disturb cell viability, therefore PG is one of the main targets of antimicrobial drugs. Considering its major role in cell structure and integrity, the study of PG is of utmost relevance, with prospective ramifications to several disciplines such as microbiology, pharmacology, agriculture, and pathogenesis. Traditionally, high-performance liquid chromatography (HPLC) has been the workhorse of PG analysis. In recent years, technological and bioinformatic developments have upgraded this seminal technique, making analysis more sensitive and efficient than ever before. Here we describe a set of analytical tools for the study of PG structure (from composition to 3D architecture), identify the most recent trends, and discuss future challenges in the field.

Thermo-kinetics and gaseous product analysis of banana peel pyrolysis for its bioenergy potential

This study illustrated the pyrolysis of banana peel (BP) as a potential waste management solution. Samples were characterized through Fourier transform infrared spectrometry (FTIR), elemental analysis, and high heating value (HHV) calculation. After pyrolysis experiments were performed at different heating rates (10, 20, 30, and 40 °C min−1) by using a thermogravimetric analyzer coupled with FTIR (TG-FTIR), the apparent activation energies were computed with Friedman, Kissinger–Akahira–Sunose (KAS), and Flynn–Wall–Ozawa (FWO) methods, and the evolved gaseous products were analyzed simultaneously. During pyrolysis, BP underwent three devolatilization steps accompanied by the evolution of some major gaseous products, including CO2, CH4, H2O, CH3COOH, CC, C6H5OH, HCOOH, and CH3CH2OH. Among them, CC, CH3COOH, and CO2 accounted for approximately 71.56% of the total gaseous products. Gas evolution was more significantly influenced by the pyrolysis temperature than by the heating rate. Pyrolysis–gas chromatography/mass spectrometry (Py-GC/MS) analysis confirmed the presence of some high-energy compounds and valuable chemicals containing aromatic, aldehyde, ketone, and other functional groups. In terms of preliminary energy balance, more than 70% of the total energy output was attributed to the liquid pyrolytic products followed by the solid and gaseous products. The energy recovery ratio of BP pyrolysis was superior to that of other fuel feedstocks. This work provided insights into resolving environmental problems associated with BP management by pyrolyzing BP as a potential source of renewable bioenergy.

Synthesis and Evaluation of RhxSy Catalyst with High Affinity for Nafion Ionomer for HOR/HER in a H2-Br2 Regenerative Fuel Cell

Synthesis and evaluation of RhxSy with high mass-specific electrochemical surface area (ECSA/mass) and high affinity to Nafion polymer are reported. Besides the previously reported supporting carbon functionalization, the nanoparticle size was optimized by a diffusion-controlled growth process to control Rh2S3 monomer concentration, which reduced the average particle size from 13.2 to 5.2 nm and increased the ECSA/mass from 9.1 to 36.5 m2/g-Rh. The affinity issue between the surface ketone functional group and the Nafion ionomer in the catalyst ink was resolved by using the Baeyer-Villiger reaction and ester hydrolysis to convert it to the Nafion-friendly carboxylic group with no adverse effect on the precipitated catalysts. The H2-Br2 fuel cell tests confirmed that the high mass transfer issue observed with the RhxSy catalysts on ketone-dominated carbon substrate was resolved with the new catalysts, validating the hypothesis that the low affinity to Nafion polymer of the surface ketone group was the cause for the formation of thick Nafion polymer layer on the catalyst surface and high mass transportation resistance. Using the new catalyst, the discharge performance of the H2-Br2 fuel cell improved by 5.6 times (0.15 vs. 0.027 A/cm2 at 0.2 V below OCV) over that of the fuel cell with the RhxSy/untreated carbon catalyst.

Second-Generation Nanosponges: Nanonetworks in Controlled Dimensions via Backbone Ketoxime and Alkoxyamine Cross-Links for Controlled Release

We report the synthesis of nanoparticle (NP) networks in a variety of sizes through the controlled cross-linking reaction of ketone groups integrated into linear polyester backbones and a difunctionalized aminooxy ethylene cross-linker. In contrast to previous work forming nanonetworks from linear components with pendant reactive groups, the ketone functional group is part of the polymer backbone accomplished by copolymerization of 2-oxepane-1,5-dione (OPD) monomers together with δ-valerolactone. This process precludes postpolymerization reactions, modifying pendant functional groups in the polyester component, and provides direct access to the cross-linking entity. Reactions with bis(aminooxy)poly(ethylene glycol) form networks in a rapidly proceeding process with linear precursors containing 4%, 8%, and 14% of OPD, in a ratio of two aminooxy groups per keto group. The concentration of the OPD unit in solution is another critical factor contributing to the controlled production of these particles as investigated in two conditions to yield a set of six particles in well-defined dimensions ranging from 39 to 173 nm. Ketoxime linkages are pH-responsive and provide an alternative faster degradation mechanism together with a hydrolysis of the polymer backbone. The reduction of the ketoxime linkages after nanoparticle formation resulted in an additional set of six particles in comparable sizes with stable alkoxyamine groups limiting the degradation to a slower hydrolysis. In this work, we prepared a series of twelve particles in a two- or three-step process starting from the synthesis of three different OPD-containing polymers and controlled cross-linking in two reaction concentrations, with or without reduction of the ketoxime connective group. These particles are promising drug delivery systems as a practical synthesis is combined with a tunable degradation leading to expanded options for drug release and is demonstrated in the release of the natural product Brefeldin A.

New sensitive strategy for formaldehyde sensing by in situ generation of luminescent silver nanoclusters

A new strategy for the detection of formaldehyde (FA) based on in situ generation of fluorescent silver nanoclusters (AgNCs) was demonstrated by using modified Tollens’ reagent. Tollens’ reagent is a reagent commonly used to distinguish between aldehyde and ketone functional groups. A silver mirror will be observed on a test tube surface if the sample contains aldehyde groups. However, in this method, the Tollens’ reagent was modified with polymethacrylic acid (PMAA), which acts as a template to generate fluorescent AgNCs instead of a silver mirror upon reaction with FA. In the presence of FA, Tollens’ reagent will be converted to AgNCs and the fluorescent emissions can be recorded. The fluorescence intensity of the generated AgNCs linearly increased as a function of the FA concentration. Parameters that may affect the detection sensitivity were studied and optimized. The proposed method has excellence selectivity for the detection of FA over other compounds. The proposed strategy exhibited a linear working concentration range of 1.0–9.0 μM with a detection limit of 0.14 μM and can be efficiently used to detect FA in bean sprout samples with a satisfactory accuracy. This proposed method does not require a complicated sensor probe preparation and enhances the FA detection selectivity and sensitivity.

Accounting for cross association in non-self-associating species using a physically consistent SAFT-VR Mie approach

This work presents a formalised, physically consistent approach to account for cross association in the SAFT framework. The focus of the approach was to account for solvation of non-self-associating components, using members of the ketone and ether functional groups as model components. Physical consistency is captured by only considering a single negative site in these components, with the association mechanisms termed the “N scheme” as a result. An accurate polar parameter set is a prerequisite for the approach, where polar and dispersion interactions are already accounted for in pure component properties and those of mixtures where solvation is absent. Using SAFT-VR Mie-GV as the example framework, the approach considers the discretisation of the two association parameters, and it applies the resulting matrix of parameter sets to mixture VLE data for the ketone or ether with alcohols in the C2 to C4 range. Analysis of the resulting AAD contour plots demonstrate that the use of average solvation parameters for each functional groups are appropriate, rather than component-specific parameters, and they offer excellent pure predictions for alcohol mixtures and good predictions for aqueous mixtures. As a final test, the approach was applied to chloroform, considering a single positive site and using the proposed parameterisation method. The resulting “P scheme” for chloroform, in conjunction with the N scheme for acetone, yields excellent predictions for the quintessential chloroform/acetone mixture and emphasises the suitability and predictive strength of the approach.

Cobalt-Catalyzed Hydroboration of Alkenes, Aldehydes, and Ketones.

An operationally convenient and general method for hydroboration of alkenes, aldehydes, and ketones employing Co(acac)3 as a precatalyst is reported. The hydroboration of alkenes in the presence of HBpin, PPh3, and NaO tBu affords good to excellent yields with high Markovnikov selectivity with up to 97:3 branched/linear selectivity. Moreover, Co(acac)3 could be used effectively to hydroborate aldehydes and ketones in the absence of additives under mild reaction conditions. Inter- and intramolecular chemoselective reduction of the aldehyde group took place over the ketone functional group.

Two New Steroidal Saponins from Solanum procumbens

Two new steroidal saponins, solaprocumosides A (1) and B (2), and a known compound paniculonin B (3) were isolated from the aerial parts of Solanum procumbens. Their chemical structures were determined by analysis of HR-ESI-MS and NMR spectra. Compound 1 had ketone functional groups at C-16 and C-22 of sterol skeleton which is rarely found in nature. Meanwhile, compound 2 could be form by oxidative breakdown C-20/C-22 bonding of a furostane-type saponin. Compounds 1–3 showed weak cytotoxicity against HepG2 cell line with IC50 values of 55.7 ± 1.5, 48.1 ± 2.2, and 78.3 ± 2.4 μM, respectively.

Examination of the electronic structure of oxygen-containing PAH dimers and trimers

Interactions of oxygen with polynuclear aromatic hydrocarbons (PAH) can occur both in the flame and during oxidation of soot atmospherically. Past experimental measurements of PAH in soot samples collected either immediately after combustion, from the atmosphere, or in a flame show a variety of oxygen moieties within the PAH structures. This study investigated the electronic structure of oxygen-containing PAH to gain insight into their interaction with light both to better interpret spectroscopic measurements and to recognize the role of oxygen-containing PAH in atmospheric radiative forcing. Our research has shown that oxygen in ethers and hydroxyl moieties on PAH showed little change to the HOMO-LUMO gap (HLG), whereas ketones and aldehydes show a HLG decrease of 0.5 eV. The effect is enhanced when more than one ketone is present on a PAH molecule and further enhanced in subsequent dehydrogenation to a quinone-like structure. The presence of an oxygen-containing PAH with a ketone functional group in a dimer and trimer will substantially lower the HLG of the PAH stack. This may have a significant effect in the interaction of atmospheric soot with solar radiation.

A novel strategy for the asymmetric synthesis of (S)-ketamine using (S)-tert-butanesulfinamide and 1,2-cyclohexanedione

We present a novel asymmetric synthesis route for synthesis of (S)-ketamine using a chiral reagent according to the strategy (Scheme 1), with good enantioselectivity (85% ee) and yield. In this procedure, the (S)-tert-butanesulfinamide (TBSA) acts as a chiral auxiliary reagent to generate (S)-ketamine. A series of new intermediates were synthesized and identified for the first time in this work (2–4). The monoketal intermediate (1) easily obtained after partial conversion of one ketone functional group of 1,2-cyclohexanedione into a ketal using ethylene glycol. The sulfinylimine (2) was obtained by condensation of (S)-tert-butanesulfinamide (TBSA) with (1), 4-dioxaspiro[4.5]decan-6-one in 90% yield. The (S)-N-tert-butanesulfinyl ketamine (3) was prepared on further reaction of sulfinylimine (2) with appropriate Grignard reagent (ArMgBr) in which generated chiral center in 85% yield and with 85% diastereoselectivity. Methylation of amine afforded the product (4). Finally, the sulfinyl- and ketal-protecting groups were removed from the compound (4) by brief treatment with stoichiometric quantities of HCl in a protic solvent gave the (S)-ketamine in near quantitative yield.

Isotope record of mineralogical changes in a spectrum of aqueously altered CM chondrites

The recent fall of the relatively unaltered CM chondrite Maribo provides a unique opportunity to study the early stages of aqueous alteration on the CM chondrite parent body. We show using transmission electron microscopy of a matrix FIB-section from Maribo that this meteorite mainly appears to consist of tochilinite-cronstedtite intergrowths (TCIs), but also contains regions of amorphous or nanocrystalline silicates, anhydrous silicates and FeNi metal aggregates with thin iron oxide rims, suggesting that it experienced aqueous alteration to a relatively small degree. A comparison of Maribo with increasingly altered CM chondrites such as Jbilet Winselwan and Bells shows that during progressive aqueous alteration (1) the TCIs are replaced by coarser sulfides and increasingly Mg-rich serpentine, and (2) the abundance of 15N-rich hotspots increases, whereas the magnitude of their 15N enrichment decreases. We observe that the overall N isotope variability related to aqueous alteration is an order of magnitude lower than the variability observed between different chondrite groups. We suggest these high order differences are the result of heterogeneous accretion of insoluble or soluble organic carriers of 15N to the different chondrite parent bodies. D/H ratios of matrices from Maribo, Jbilet Winselwan and Bells increase with progressive aqueous alteration, a trend that is opposite to expectations of mixing between D-poor water and D-rich organic matter. We argue that this behaviour cannot be related to Fe oxidation or serpentinization reactions and subsequent loss of D-poor H2 gas. We offer an alternative hypothesis and suggest that CM chondrites experienced two-stage aqueous alteration. During the first stage occurring at relatively low temperature, mixing of increasing amounts of D-poor water with D-rich organic matter results in a decrease of D/H ratio with increasing degree of alteration. During the second stage of alteration occurring at relatively high temperature (T < 300 °C), decomposition of TCIs in CMs of petrologic type <2.7 releases gaseous D-poor water that results in increase of the D/H ratio of the CM matrices. Finally, we report on changes in the organic structure of Maribo, Jbilet Winselwan and Bells using Carbon-K and Nitrogen-K edge electron energy loss spectroscopy. The organic matter initially has higher aromatic/aliphatic ratios (e.g., Maribo) and lower abundances of ketone and carboxyl functional groups, which we suggest are the result of chemical degradation of double bonded carbon from oxidation during hydrothermal alteration. Consequently, we propose that the organic matter of the CM chondrite Paris, for which lower aromatic/aliphatic ratios have been observed, may have been different from Maribo, perhaps reflecting the early accretion of Paris relative to Maribo.

N-Butyl levulinate synthesis using lipase catalysis: comparison of batch reactor versus continuous flow packed bed tubular microreactor

Levulinic acid and its derivatives have applications in the synthesis of various organic chemicals because of the presence of carboxylic acid and ketone functional groups in the same moiety. Levulinate esters have potential applications in biodiesel as blending components, and fragrance and flavor industries. In the present work, n-butyl levulinate was synthesized by different commercial immobilized lipases such as Rhizomucor miehei lipase (RM IM), Thermomyces lanuginosus lipase (TL IM) and Novozym 435 using a continuous flow packed bed tubular microreactor and also a stirred tank batch reactor. Novozym 435 was the best catalyst. The continuous flow tubular microreactor gave 85% conversion of levulinic acid in 2 min at 60 °C when mole ratio 1: 3 of levulinic acid to n-butanol was used in methyl tert-butyl ether (MTBE) as solvent. The batch reactor needed 2 h to achieve the same conversion thereby proving superiority of the continuous flow reactors.