Showing papers on "Carboxylic acid published in 2018"

Cytotoxicity of novel fluorinated alternatives to long-chain perfluoroalkyl substances to human liver cell line and their binding capacity to human liver fatty acid binding protein

Abstract: Although shorter chain homologues and other types of fluorinated chemicals are currently used as alternatives to long-chain perfluoroalkyl substances (PFASs), their safety information remains unclear and urgently needed. Here, the cytotoxicity of several fluorinated alternatives (i.e., 6:2 fluorotelomer carboxylic acid (6:2 FTCA), 6:2 fluorotelomer sulfonic acid (6:2 FTSA), 6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), and hexafluoropropylene oxide (HFPO) homologues) to human liver HL-7702 cell line were measured and compared with perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Their binding mode and affinity to human liver fatty acid binding protein (hL-FABP) were also determined. Compared with PFOA and PFOS, 6:2 Cl-PFESA, HFPO trimer acid (HFPO-TA), HFPO tetramer acid (HFPO-TeA), and 6:2 FTSA showed greater toxic effects on cell viabilities. At low exposure doses, these alternatives induced cell proliferation with similar mechanism which was different from that of PFOA and PFOS. Furthermore, binding affinity to hL-FABP decreased in the order of 6:2 FTCA < 6:2 FTSA < HFPO dimer acid (HFPO-DA) < PFOA < PFOS/6:2 Cl-PFESA/HFPO-TA. Due to their distinctive structure, 6:2 Cl-PFESA and HFPO homologues were bound to the hL-FABP inner pocket with unique binding modes and higher binding energy compared with PFOA and PFOS. This research enhances our understanding of the toxicity of PFAS alternatives during usage and provides useful evidence for the development of new alternatives.

Generation of Phosphoranyl Radicals via Photoredox Catalysis Enables Voltage–Independent Activation of Strong C–O Bonds

Abstract: Despite the prevalence of alcohols and carboxylic acids as functional groups in organic molecules and the potential to serve as radical precursors, C–O bonds remain difficult to activate. We report a synthetic strategy for direct access to both alkyl and acyl radicals from these ubiquitous functional groups via photoredox catalysis. This method exploits the unique reactivity of phosphoranyl radicals, generated from a polar/SET crossover between a phosphine radical cation and an oxygen-centered nucleophile. We show the desired reactivity in the reduction of benzylic alcohols to the corresponding benzyl radicals with terminal H atom trapping to afford the deoxygenated products. Using the same method, we demonstrate access to synthetically versatile acyl radicals, which enables the reduction of aromatic and aliphatic carboxylic acids to the corresponding aldehydes with exceptional chemoselectivity. This protocol also transforms carboxylic acids to heterocycles and cyclic ketones via intramolecular acyl radic...

Enantioselective Cobalt(III)-Catalyzed C−H Activation Enabled by Chiral Carboxylic Acid Cooperation

Abstract: The enantioselective cobalt(III)-catalyzed C-H alkylation was achieved through the design of a novel chiral acid. The cobalt(III)-catalyzed enantioselective C-H activation was characterized by high position-, regio- and enantio-control under exceedingly mild reaction conditions. Thereby, the robust cooperative cobalt(III) catalysis proved tolerant of valuable electrophilic functional groups, including hydroxyl, bromo, and iodo substituents. Mechanistic studies revealed a considerable additive effect on kinetics and on a negative non-linear-effect.

Aerobic Oxidation of 5-(Hydroxymethyl)furfural Cyclic Acetal Enables Selective Furan-2,5-dicarboxylic Acid Formation with CeO2-Supported Gold Catalyst

Abstract: The utilization of 5-(hydroxymethyl)furfural (HMF) for the large-scale production of essential chemicals has been largely limited by the formation of solid humin as a byproduct, which prevents the operation of stepwise batch-type and continuous flow-type processes. The reaction of HMF with 1,3-propanediol produces an HMF acetal derivative that exhibits excellent thermal stability. Aerobic oxidation of the HMF acetal with a CeO2-supported Au catalyst and Na2CO3 in water gives a 90–95 % yield of furan 2,5-dicarboxylic acid, an increasingly important commodity chemical for the biorenewables industry, from concentrated solutions (10–20 wt %) without humin formation. The six-membered acetal ring suppresses thermal decomposition and self-polymerization of HMF in concentrated solutions. Kinetic studies supported by DFT calculations identify two crucial steps in the reaction mechanism, that is, the partial hydrolysis of the acetal into 5-formyl-2-furan carboxylic acid involving OH− and Lewis acid sites on CeO2, and subsequent oxidative dehydrogenation of the in situ generated hemiacetal involving Au nanoparticles. These results represent a significant advance over the current state of the art, overcoming an inherent limitation of the oxidation of HMF to an important monomer for biopolymer production.

Organocatalyzed, Visible-Light Photoredox-Mediated, One-Pot Minisci Reaction Using Carboxylic Acids via N-(Acyloxy)phthalimides.

Abstract: An improved, one-pot Minisci reaction has been developed using visible light, an organic photocatalyst, and carboxylic acids as radical precursors via the intermediacy of in situ-generated N-(acyloxy)phthalimides. The conditions employed are mild, demonstrate a high degree of functional group tolerance, and do not require a large excess of the carboxylic acid reactant. As a result, this reaction can be applied to drug-like scaffolds and molecules with sensitive functional groups, enabling late-stage functionalization, which is of high interest to medicinal chemistry.

Pd II -Catalyzed Enantioselective C(sp 3 )-H Activation/Cross-Coupling Reactions of Free Carboxylic Acids

Abstract: PdII -catalyzed enantioselective C(sp3 )-H cross-coupling of free carboxylic acids with organoborons has been realized using either mono-protected amino acid (MPAA) ligands or mono-protected aminoethyl amine (MPAAM) ligands. A diverse range of aryl- and vinyl-boron reagents can be used as coupling partners to provide chiral carboxylic acids. This reaction provides an alternative approach to the enantioselective synthesis of cyclopropanecarboxylic acids and cyclobutanecarboxylic acids containing α-chiral tertiary and quaternary stereocenters. The utility of this reaction was further demonstrated by converting the carboxylic acid into cyclopropyl amine without loss of optical activity.

Enantiodivergent Desymmetrization in the Rhodium(III)‐Catalyzed Annulation of Sulfoximines with Diazo Compounds

Abstract: RhIII - and IrIII -catalyzed asymmetric C-H functionalization reactions of arenes have relied on the employment of chiral RhIII /IrIII cyclopentadienyl catalysts, the introduction of chiral carboxylic acids to achiral Cp*RhX2 catalysts, and the integration of both strategies. Despite considerable progress, each reaction only provided a specific configuration of the enantioenriched product when using a particular chiral catalyst. Reported in this work is the enantiodivergent coupling of sulfoximines with various diazo compounds by RhIII -catalyzed desymmetrizing annulation. The enantiodivergence was enabled by a judicious choice of achiral carboxylic acids, and the enantioselectivity correlates with the steric bias of the carboxylic acid and the sulfoximine.

Catalytic Carbo- and Aminoboration of Alkenyl Carbonyl Compounds via Five- and Six-Membered Palladacycles

Abstract: A palladium(II)-catalyzed alkene difunctionalization reaction has been developed, wherein B2pin2 is used to trap chelation-stabilized alkylpalladium(II) intermediates that are formed upon nucleopalladation A range of carbon and nitrogen nucleophiles were found to be suitable coupling partners in this transformation, providing moderate to high yields Both 3-butenoic and 4-pentenoic acid derivatives were reactive substrate classes, affording β,γ- and γ,δ-difunctionalized carboxylic acid derivatives This work represents a new strategy to synthesize highly functionalized secondary boronates that complements existing methods

Palladium(II)‐Catalyzed Enantioselective Arylation of Unbiased Methylene C(sp3)−H Bonds Enabled by a 2‐Pyridinylisopropyl Auxiliary and Chiral Phosphoric Acids

Abstract: Enantioselective functionalizations of unbiased methylene C(sp3 )-H bonds of linear systems by metal insertion are intrinsically challenging and remain a largely unsolved problem. Herein, we report a palladium(II)-catalyzed enantioselective arylation of unbiased methylene β-C(sp3 )-H bonds enabled by the combination of a strongly coordinating bidentate PIP auxiliary with a monodentate chiral phosphoric acid (CPA). The synergistic effect between the PIP auxiliary and the non-C2 -symmetric CPA is crucial for effective stereocontrol. A broad range of aliphatic carboxylic acids and aryl bromides can be used, providing β-arylated aliphatic carboxylic acid derivatives in high yields (up to 96 %) with good enantioselectivities (up to 95:5 e.r.). Notably, this reaction also represents the first palladium(II)-catalyzed enantioselective C-H activation with less reactive and cost-effective aryl bromides as the arylating reagents. Mechanistic studies suggest that a single CPA is involved in the stereodetermining C-H palladation step.

Chiral Carboxylic Acid Enabled Achiral Rhodium(III)-Catalyzed Enantioselective C−H Functionalization

Abstract: Reported is an achiral Cpx RhIII /chiral carboxylic acid catalyzed asymmetric C-H alkylation of diarylmethanamines with a diazomalonate, followed by cyclization and decarboxylation to afford 1,4-dihydroisoquinolin-3(2H)-one. Secondary alkylamines as well as nonprotected primary alkylamines underwent the transformation with high enantioselectivities (up to 98.5:1.5 e.r.) by using a newly developed chiral carboxylic acid as the sole source of chirality to achieve enantioselective C-H cleavage by a concerted metalation-deprotonation mechanism.

High-Performance Soybean-Oil-Based Epoxy Acrylate Resins: “Green” Synthesis and Application in UV-Curable Coatings

Abstract: Novel soybean-oil-based (SBO-based) epoxy acrylate (EA) resins were developed via ring-opening reaction of epoxidized soybean oil (ESO) with hydroxyethyl methacrylated maleate (HEMAMA) precursor, a synthesized unsaturated carboxylic acid having two active C═C groups and a side methyl group. Experimental conditions for the synthesis of the precursor and the SBO-based EA (ESO-HEMAMA) product were studied, and their chemical structures were confirmed by FT-IR, 1H NMR, 13C NMR, and gel permeation chromatography. Subsequently, the volatility of HEMAMA was studied and compared with acrylic acid (AA). Furthermore, gel contents and ultimate properties of the UV-cured ESO-HEMAMA resins were investigated and compared with a commercial acrylated ESO (AESO) resin. At last, UV-curing behaviors of the SBO-based EA resins were determined by real-time IR. It was found that the HEMAMA precursor showed much lower volatility than AA, and the optimal pure ESO-HEMAMA resin possessed a C═C functionality up to 6.02 per ESO and ...

Palladium-Catalyzed Direct Synthesis of Various Branched, Carboxylic Acid-Functionalized Polyolefins: Characterization, Derivatization, and Properties

Abstract: Ethylene-co-acrylic acid (E–AA) copolymers are typically produced via high-pressure free radical copolymerization and have great industrial importance because of their many applications. The radical polymerization mechanism usually leads to highly branched products with poor mechanical properties. Transition-metal-catalyzed E–AA copolymerization represents a direct and economical route to access these copolymers with potentially better control over their microstructures and material properties. However, this is highly challenging due to catalyst poisoning from both the oxygen and carboxylic acid moieties in the monomers. In this contribution, we demonstrate that a series of α-diimine-based palladium catalysts can mediate efficient copolymerizations of ethylene with AA, allylacetic acid, and 10-undecenoic acid, leading to the formation of various branched, carboxylic acid-functionalized polyolefin materials. These comonomers exist as carboxylic acid-based dimeric species at ambient temperatures, which is p...

Amino acid disorders

Abstract: Amino acids serve as key building blocks and as an energy source for cell repair, survival, regeneration and growth. Each amino acid has an amino group, a carboxylic acid, and a unique carbon structure. Human utilize 21 different amino acids; most of these can be synthesized endogenously, but 9 are “essential” in that they must be ingested in the diet. In addition to their role as building blocks of protein, amino acids are key energy source (ketogenic, glucogenic or both), are building blocks of Kreb’s (aka TCA) cycle intermediates and other metabolites, and recycled as needed. A metabolic defect in the metabolism of tyrosine (homogentisic acid oxidase deficiency) historically defined Archibald Garrod as key architect in linking biochemistry, genetics and medicine and creation of the term ‘Inborn Error of Metabolism’ (IEM). The key concept of a single gene defect leading to a single enzyme dysfunction, leading to “intoxication” with a precursor in the metabolic pathway was vital to linking genetics and metabolic disorders and developing screening and treatment approaches as described in other chapters in this issue. Amino acid disorders also led to the evolution of the field of metabolic nutrition and offending amino acid restricted formula and foods. This review will discuss the more common disorders caused by inborn errors in amino acid metabolism.

Palladium-Catalyzed Decarbonylative Borylation of Carboxylic Acids: Tuning Reaction Selectivity by Computation.

Abstract: Decarbonylative borylation of carboxylic acids is reported. Carbon electrophiles are generated directly after reagent-enabled decarbonylation of the in situ accessible sterically-hindered acyl derivative of a carboxylic acid under catalyst controlled conditions. The scope and the potential impact of this method are demonstrated in the selective borylation of a variety of aromatics (>50 examples). This strategy was used in the late-stage derivatization of pharmaceuticals and natural products. Computations reveal the mechanistic details of the unprecedented C-O bond activation of carboxylic acids. By circumventing the challenging decarboxylation, this strategy provides a general synthetic platform to access arylpalladium species for a wide array of bond formations from abundant carboxylic acids. The study shows a powerful combination of experiment and computation to predict decarbonylation selectivity.

Systematic investigation of functional ligands for colloidal stable upconversion nanoparticles

Abstract: Despite intense efforts on surface functionalization to generate hydrophilic upconversion nanoparticles (UCNPs), long-term colloidal stability in physiological buffers remains a major concern. Here we quantitatively investigate the competitive adsorption of phosphate, carboxylic acid and sulphonic acid onto the surface of UCNPs and study their binding strength to identify the best conjugation strategy. To achieve this, we designed and synthesized three di-block copolymers composed of poly(ethylene glycol) methyl ether acrylate and a polymer block bearing phosphate, carboxylic or sulphonic acid anchoring groups prepared by an advanced polymerization technique, Reversible Addition Fragmentation Chain Transfer (RAFT). Analytical tools provide the evidence that phosphate ligands completely replaced all the oleic acid capping molecules on the surface of the UCNPs compared with incomplete ligand exchange by carboxylic and sulphonic acid groups. Meanwhile, simulated quantitative adsorption energy measurements confirmed that among the three functional groups, the calculated adsorption strength for phosphate anchoring ligands is higher which is in good agreement with experimental results regarding the best colloidal stability, especially in phosphate buffer solution. This finding suggests that polymers with multiple anchoring negatively charged phosphate moieties provide excellent colloidal stability for lanthanide ion-doped luminescent nanoparticles for various potential applications.

Carboxylic acid-modified metal oxide catalyst for selectivity-tunable aerobic ammoxidation.

Abstract: Controlling the reaction selectivity of a heterobifunctional molecule is a fundamental challenge in many catalytic processes. Recent efforts to design chemoselective catalysts have focused on modifying the surface of metal nanoparticle materials having tunable properties. However, precise control over the surface properties of base-metal oxide catalysts remains a challenge. Here, we show that green modification of the surface with carboxylates can be used to tune the ammoxidation selectivity toward the desired products during the reaction of hydroxyaldehyde on manganese oxide catalysts. These modifications improve the selectivity for hydroxynitrile from 0 to 92% under identical reaction conditions. The product distribution of dinitrile and hydroxynitrile can be continuously tuned by adjusting the amount of carboxylate modifier. This property was attributed to the selective decrease in the hydroxyl adsorption affinity of the manganese oxides by the adsorbed carboxylate groups. The selectivity enhancement is not affected by the tail structure of the carboxylic acid.

Functionalized Covalent Triazine Frameworks for Effective CO2 and SO2 Removal.

Abstract: Building novel frameworks as sorbents remains a highly significant target for key environmental issues such as CO2 or SO2 emissions from coal-fired power plants. Here, we report the construction and tunable pore structure as well as gas adsorption properties of hierarchically porous covalent triazine-based frameworks (CTF-CSUs) functionalized by appended carboxylic acid/sodium carboxylate groups. The densely integrated functionalities on the pore walls bestow strong affinity to the as-made networks toward guest acid gases, in spite of their moderate Brunauer–Emmett–Teller surface areas. With abundant microporosity and integrated carboxylic acid groups, our frameworks deliver strong affinity toward CO2 with considerably high enthalpy (up to 44.6 kJ/mol) at low loadings. Moreover, the sodium carboxylate-anchored framework (termed as CTF-CSU41) shows an exceptionally high uptake of SO2 up to 6.7 mmol g–1 (42.9 wt %) even under a low SO2 partial pressure of 0.15 bar (298 K), representing the highest value for...

Mechanistic Insights into the Enantioselective Epoxidation of Olefins by Bioinspired Manganese Complexes: Role of Carboxylic Acid and Nature of Active Oxidant

Abstract: Bioinspired manganese and iron complexes bearing nonporphyrinic tetradentate N4 ligands are highly efficient catalysts in asymmetric oxidation reactions by hydrogen peroxide (H2O2), in which carboxylic acid is employed as an essential additive to improve product yields and stereo-, regio-, and enantioselectivities. The metal catalysts should possess two cis-binding sites for oxidant (e.g., H2O2) and carboxylic acid to generate high-valent metal-oxo species as active oxidants via a “carboxylic acid-assisted” mechanism. In the present study, we have investigated the role(s) of carboxylic acid and the nature of reactive intermediate(s) in the manganese complex-catalyzed enantioselective epoxidation of olefins, by employing non-heme manganese catalysts, such as 1 bearing a tetradentate N4 ligand (LN4) and 2 bearing a pentadentate N5 ligand (LN5), and using various oxidants, such as H2O2, alkyl hydroperoxides, and iodosylbenzene (PhIO). As expected, 1 possessing two cis-binding sites is an effective catalyst i...

Iridium Catalysts for Acceptorless Dehydrogenation of Alcohols to Carboxylic Acids: Scope and Mechanism

Abstract: We introduce iridium-based conditions for the conversion of primary alcohols to potassium carboxylates (or carboxylic acids) in the presence of potassium hydroxide and either [Ir(2-PyCH2(C4H5N2))(COD)]OTf (1) or [Ir(2-PyCH2PBu2t)(COD)]OTf (2). The method provides both aliphatic and benzylic carboxylates in high yield and with outstanding functional group tolerance. We illustrate the application of this method to a diverse variety of primary alcohols, including those involving heterocycles and even free amines. Complex 2 reacts with alcohols to form the crystallographically characterized catalytic intermediates [IrH(η1,η3-C8H12)(2-PyCH2PtBu2)] (2a) and [Ir2H3(CO)(2-PyCH2PtBu2){μ-(C5H3N)CH2PtBu2}] (2c). The unexpected similarities in reactivities of 1 and 2 in this reaction, along with synthetic studies on several of our iridium intermediates, enable us to form a general proposal of the mechanisms of catalyst activation that govern the disparate reactivities of 1 and 2, respectively, in glycerol and formic ...

Mechanistic insights into boron-catalysed direct amidation reactions

Abstract: The generally accepted monoacyloxyboron mechanism of boron-catalysed direct amidation is brought into question in this study, and new alternatives are proposed. We have carried out a detailed investigation of boron-catalysed amidation reactions, through study of the interaction between amines/carboxylic acids and borinic acids, boronic acids and boric acid, and have isolated and characterised by NMR/X-ray crystallography many of the likely intermediates present in catalytic amidation reactions. Rapid reaction between amines and boron compounds was observed in all cases, and it is proposed that such boron-nitrogen interactions are highly likely to take place in catalytic amidation reactions. These studies also clearly show that borinic acids are not competent catalysts for amidation, as they either form unreactive amino-carboxylate complexes, or undergo protodeboronation to give boronic acids. It therefore seems that at least three free coordination sites on the boron atom are necessary for amidation catalysis to occur. However, these observations are not consistent with the currently accepted 'mechanism' for boron-mediated amidation reactions involving nucleophilic attack of an amine onto a monomeric acyloxyboron intermediate, and as a result of our observations and theoretical modelling, alternative proposed mechanisms are presented for boron-mediated amidation reactions. These are likely to proceed via the formation of a dimeric B-X-B motif (X = O, NR), which is uniquely able to provide activation of the carboxylic acid, whilst orchestrating the delivery of the amine nucleophile to the carbonyl group. Quantum mechanical calculations of catalytic cycles at the B3LYP+D3/Def2-TZVPP level (solvent = CH2Cl2) support the proposal of several closely related potential pathways for amidation, all of which are likely to be lower in energy than the currently accepted mechanism.

Catalytic Asymmetric Synthesis of Trifluoromethylated γ-Amino Acids through the Umpolung Addition of Trifluoromethyl Imines to Carboxylic Acid Derivatives.

Abstract: Novel cinchona alkaloid derived chiral phase-transfer catalysts enabled the highly chemo-, regio-, diastereo-, and enantioselective umpolung addition of trifluoromethyl imines to α,β-unsaturated N-acyl pyrroles. With a catalyst loading ranging from 0.2 to 5.0 mol %, this new catalytic asymmetric transformation provides facile and high-yielding access to highly enantiomerically enriched chiral trifluoromethylated γ-amino acids and γ-lactams.