Related Carboxylic Acids Research Articles

Nitrile Furanics via Copper‐Catalyzed Dehydration of Aldoximes and Knoevenagel Condensation

AbstractIn this work two synthetic approaches to introduce nitrile moieties into bio‐based derived furanic compounds were investigated, i. e., dehydration of aldoximes and Knoevenagel condensation. Both methodologies have been first tested and optimized on furfural and thus exploited on 5‐hydroxymethyl‐2‐furfural (HMF) and 5,5’‐oxy(bismethylene)‐2‐furaldehyde (OBMF). The syntheses of furfural, HMF and OBMF aldoximes were efficiently conducted (also in large scale) under mild reaction conditions and short reaction time. The subsequent dehydration to nitrile furanic compounds was carried out in the presence of catalytic amount of copper acetate monohydrate. Furthermore, Knoevenagel condensations were performed on furfural, HMF and OBMF with different Activated Methylene Group compounds, using for the first‐time dimethyl carbonate as the reaction media. Most of the resulting products were isolated as pure via simple liquid‐liquid extraction in good to excellent yields. Future applications of these compounds might include aldoxime reduction into amine furanics ‐ herein also preliminary investigated ‐ and hydrolysis of the nitrile derivatives in the related carboxylic acid (or ester) furanics. All these products are interesting monomers for the preparation of bio‐based polymers.

Uncovering the toxicity mechanisms of a series of carboxylic acids in liver cells through computational and experimental approaches

Hepatotoxicity poses a significant concern in drug design due to the potential liver damage that can be caused by new drugs. Among common manifestations of hepatotoxic damage is lipid accumulation in hepatic tissue, resulting in liver steatosis or phospholipidosis. Carboxylic derivatives are prone to interfere with fatty acid metabolism and cause lipid accumulation in hepatocytes. This study investigates the toxic behaviour of 24 structurally related carboxylic acids in hepatocytes, specifically their ability to cause accumulation of fatty acids and phospholipids. Using high-content screening (HCS) assays, we identified two distinct lipid accumulation patterns. Subsequently, we developed structure-activity relationship (SAR) and quantitative structure-activity relationship (QSAR) models to determine relevant molecular substructures and descriptors contributing to these adverse effects. Additionally, we calculated physicochemical properties associated with lipid accumulation in hepatocytes and examined their correlation with our chemical structure characteristics. To assess the applicability of our findings to a wide range of chemical compounds, we employed two external datasets to evaluate the distribution of our QSAR descriptors. Our study highlights the significance of subtle molecular structural variations in triggering hepatotoxicity, such as the presence of nitrogen or the specific arrangement of substitutions within the carbon chain. By employing our comprehensive approach, we pinpointed specific molecules and elucidated their mechanisms of toxicity, thus offering valuable insights to guide future toxicology investigations.

The effects of aliphatic alcohols and related acid metabolites in zebrafish embryos - correlations with rat developmental toxicity and with effects in advanced life stages in fish

The zebrafish embryo toxicity test (ZFET) is a simple medium-throughput test to inform about (sub)acute lethal effects in embryos. Enhanced analysis through morphological and teratological scoring, and through gene expression analysis, detects developmental effects and the underlying toxicological pathways. Altogether, the ZFET may inform about hazard of chemical exposure for embryonal development in humans, as well as for lethal effects in juvenile and adult fish. In this study, we compared the effects within a series of 12 aliphatic alcohols and related carboxylic acid derivatives (ethanol, acetic acid, 2-methoxyethanol, 2-methoxyacetic acid, 2-butoxyethanol, 2-butoxyacetic acid, 2-hydroxyacetic acid, 2-ethylhexan-1-ol, 2-ethylhexanoic acid, valproic acid, 2-aminoethanol, 2-(2-hydroxyethylamino)ethanol) in ZFET and early life stage (ELS, 28d) exposures, and compared ZFET results with existing results of rat developmental studies and LC50s in adult fish. High correlation scores were observed between compound potencies in ZFET with either ELS, LC50 in fish and developmental toxicity in rats, indicating similar potency ranking among the models. Compounds could be mapped to specific pathways in an adverse outcome pathway (AOP) network through morphological scoring and gene expression analysis in ZFET. Similarity of morphological effects and gene expression profiles in pairs of alcohols with their acid metabolites suggested metabolic activation of the parent alcohols, although with additional, metabolite-independent activity independent for ethanol and 2-ethylhexanol. Overall, phenotypical and gene expression analysis with these compounds indicates that the ZFET can potentially contribute to the AOP for developmental effects in rodents, and to predict toxicity of acute and chronic exposure in advanced life stages in fish.

Photoredox Catalytic Trifluoromethylation and Perfluoroalkylation of Arenes Using Trifluoroacetic and Related Carboxylic Acids

Summary Trifluoroacetic acid (TFA) is among the most attractive trifluoromethylation reagents with respect to its low prices, ease of handling, and availability in large quantities. However, because of its exceedingly high oxidation potential, harsh conditions are required for the direct oxidation of TFA to the trifluoroacetate radical, which after prompt CO2 extrusion, affords the desired CF3 radical. Therefore, mild and efficient protocols for the direct conversion of TFA to the CF3 radical are still in high demand. Here, we report a mild and practical method that allows for the direct C–H trifluoromethylation, perfluoroalkylation, and chlorodifluoromethylation of (hetero)arenes using TFA and the related carboxylic acids. A diverse array of arenes and heteroarenes were successfully transformed into valued fluoroalkylated compounds. The combination of photoredox catalysis and a diaryl sulfoxide provides a platform for the facile generation of fluoroalkyl radicals from the corresponding fluoroalkyl carboxylic acids under mild conditions.

Reactions of NHC‐Boranes with Dibenzoyl Peroxide and Benzoic Acid

AbstractNHC‐boranes (NHC−BH3) react slowly under thermal conditions with dibenzoyl peroxide to make mixtures of NHC‐boryl mono‐ and dibenzoates [NHC−BH2OBz and NHC−BH(OBz)2]. Reactions are much faster under radical conditions with AIBN of TBHN as initiators. The TBHN method is especially good to make the dibenzoate. These observations led directly to the discovery that NHC‐boranes also react with benzoic acid and related carboxylic acids under radical (but not thermal) conditions. Chain mechanisms for reactions with both reagents are suggested in which the key step is addition of an NHC‐boryl radical to the carbonyl oxygen of either the peroxide or the acid.magnified image

Double decarboxylative route to 3-substituted pyrrolidines: Reaction of monoalkyl malonates and related carboxylic acids with sarcosine and formaldehyde

Three-component reactions of monoalkyl malonates, cyanoacetic acids or 2-ketocarboxylic acids, N-methylglycine, and formaldehyde were developed to rapidly access 3-substituted pyrrolidines in 17–97% yield. These reactions represent a double decarboxylative domino-sequence promoted by pyrrolidine and involve N-methylazomethine ylide as the reactive intermediate.

Impurity profiling of l-aspartic acid and glycine using high-performance liquid chromatography coupled with charged aerosol and ultraviolet detection

For the compendial related substances test of l-aspartic acid (Asp) and glycine (Gly), two separate reversed-phase ion-pair high-performance liquid chromatography methods coupled with charged aerosol and ultraviolet detection were developed. Separation of all putative impurities, in particular of the related carboxylic and amino acids, was achieved using volatile perfluorocarboxylic acids as ion-pairing reagents on a polar embedded C18 stationary phase. It was shown that an adjustment of the evaporation temperature of the charged aerosol detector (CAD) was an efficient strategy for meeting the required quantitation limits, when dealing with non-volatile analytes. It was also demonstrated that the usage of a two detector setup can be beneficial for extending the detection range and providing accurate quantitation of low level impurities (LOQs from 5 to 50 ng on column). Both methods were validated with accordance to ICH guideline Q2(R1) assessing specificity, linearity, accuracy, precision, and robustness. Several batches of Asp and Gly were tested for related substances using the developed methods. The purity of each sample was higher than 99.7 %. Coupled charged aerosol and UV detection proved to be a more simple, robust and selective alternative to established derivatization procedures such as the Amino-Acid-Analyser (AAA) for the impurity profiling of amino acids, and should thus be considered for implementation into pharmacopoeial monographs in the future.

Photoredox Catalytic Trifluoromethylation and Perfluoroalkylation of (Hetero)Arenes Using Trifluoroacetic and Related Carboxylic Acids

A mild and practical method has been achieved that allows for the direct C–H trifluoromethylation, perfuoroalkylation and chlorodifluoromethylation of (hetero)arenes using inexpensive, abundant trifluoroacetic acid and the related carboxylic acids. A diverse array of arenes and heteroarenes were successfully transformed into valued fluoroalkylated compounds. The combination of photoredox catalysis and a diaryl sulfoxide provides a platform for the facile generation of fluoroalkyl radicals from the corresponding fluoroalkyl carboxylic acids under mild conditions.

A versatile method for the synthesis of poly(glycolic acid): high solubility and tunable molecular weights

Poly(glycolic acid) (PGA) is an important biopolymer, especially in medical applications because of its suitable mechanical, biocompatible, and biodegradable properties. PGA can degrade within weeks, depending on its molecular weight. Production of high molecular weight PGA is important to achieve sufficient mechanical stability for biomedical applications. High molecular weight PGA is difficult to obtain by direct condensation of the related carboxylic acids; therefore, polyglycolide is typically made by ring opening polymerization of the cyclic diester glycolide. However, this procedure is restrictive because of the high cost of the raw material (glycolide) and the associated high energy consumption. Here, we describe the synthesis of PGA via an azeotropic distillation method that enables tunable molecular weights. The synthesized PGA is highly soluble in organic solvents and degrades faster than reference PGA. We described the synthesis of PGA via an azeotropic distillation method that enables tunable molecular weights. This alternative method produces a white powdered PGA rather than a waxy brown product that is obtained by conventional melt-solid condensation methods. Additionally, improved solubility renders this method useful for producing soluble high molecular weight PGA for further applications. Highly crystalline PGA with a high molecular weight (Mn = 32,100 g/mol) was obtained with a homogenous polydispersity index of 1.2–1.4.

(Invited) Controlling Optical Properties of Semiconductor Nanocrystals: Chiral Quantum Dots and Luminescent Solar Concentrators

This talk will discuss two areas of research in utilizing semiconductor nanocrystals in nanophotonics. The first part of the talk will describe our recent work on chiral semiconductor nanocrystals. Chiral optical materials exhibit differential optical properties under right handed and left handed circularly polarized light, and may find application in metaphotonic devices, in spin-based systems, or as luminescent sensors. Chirality can be introduced into semiconductor nanocrystals via different routes, including from chiral ligands on the surface of the nanocrystal. However, the application of these materials in photonics is limited by the relatively low dissymmetry factors. Using post-synthetic ligand exchange, we synthesized a class of chiral CdSe nanocrystals with a variety of different chiral ligands bound to the surface. We first synthesized CdSe nanocrystals via non-hot injection methods, with native, achiral carboxylic acids on the surface. As synthesized, these nanocrystals do not exhibit any circular dichroism. Post-synthetic ligand exchange of the native ligands to chiral carboxylic acids results in circular dichroism spectra associated with the excitonic transitions of the CdSe nanocrystal. We examine a family of related carboxylic acid ligands, which reveal a 30-fold difference in dissymmetry factors, reaching as high as 7 x 10-4, and show how the structure of the ligands influences the resulting circular dichroism spectra. The second part of the talk will discuss the use of luminescent semiconductor nanocrystals in diffuse light concentrators for solar energy conversion. Luminescent solar concentrators consist of embedded luminescent materials inside a polymer waveguide, such that high energy light is absorbed by the luminophore and the emitted light is trapped within the waveguide and concentrated onto a solar cell. Efficient operation of these concentrators requires not only high quality luminescent materials, but also a photonic mirror to trap luminescent light within the concentrator. We have recently designed a series of mirrors that operate cooperatively with luminescent materials inside these concentrators, showing how the design of the mirrors changes with different luminophore properties. The top-surface mirror serves to trap luminescent light inside the concentrator that would otherwise couple to the escape cone. This light propagates at a steep angle, and is especially vulnerable to reabsorption losses before reaching the edge of the concentrator. By incorporating a metamirror into the LSC, this light can be steered toward the edge for improved collection. We show that this metamirror in turn lowers the required quantum yield; equivalent performance is achieved from a luminophore with 76% quantum yield as one in a standard design with 99% quantum yield. We then designed a series of different top mirrors for different specific properties of candidate luminophores, including Si and CdSe/CdS of varying shell thickness, showing how the luminophore and mirror can be designed cooperatively.

α-Hydroxy Ketones as Masked Ester Donors in Brønsted Base Catalyzed Conjugate Additions to Nitroalkenes.

The catalyst-controlled enantioselective direct addition reaction of enolizable esters and related carboxylic acid derivatives to π electrophiles remains a difficult synthetic transformation. In this study, the suitability of α-hydroxy ketones as ester equivalents capable of being activated by bifunctional Brønsted base catalysts in the context of conjugate addition reactions to nitroolefins is demonstrated. The scope of the reaction, which affords the corresponding Michael adducts with very high stereoselectivity (diastereomeric ratio (d.r.) ≥95:5, up to 99 % enantiomeric excess (ee)), and its limitations are explored, as is the aftermath elaboration of adducts into densely functionalized enantioenriched products.

Diffusion NMR Characterization of Catalytic Silica Supports: A Tortuous Path

Mesoporous silicas have found widespread application within the field of heterogeneous catalysis. Acid functionalization of such materials, through one-pot or postsynthetic grafting of sulfonic acid groups, imparts activity for fatty acid esterification, with the studious choice of pore geometry facilitating significant rate enhancements. Diffusion NMR has been utilized for the first time to characterize the structure of mesoporous silicas through the transport behavior of systematically related carboxylic acids confined within their mesopore networks. A reduced diffusion coefficient is obtained for species constrained within the 3-dimensional interconnected pores of KIT-6 relative to the 2-dimensional noninterconnected pore channels of SBA-15. The effective tortuosity of both porous silicas increases with the acid chain length, with the diffusion behavior of long-chain acids dominated by the alkyl chain and silica architecture. Carboxylic acid diffusion within these two pore networks is unlikely to be rate-limiting in catalytic esterification over sulfonic acid silica analogues. Physicochemical insights from diffusion NMR will aid the future design of optimal silica architectures for catalytic applications.

KEGGIN HETEROPOLY ACIDS AS AN EFFICIENT CATALYSTS FOR PHOTOCATALYTIC OXIDATION OF AROMATIC ALDEHYDES

Photocatalytic oxidation of aromatic aldehydes to related carboxylic acids was investigated in the presence of some Keggin heteroploy acids as phosphomolybdic acid H3PMo12O40 (PMo), silicotungestic acid H4SiW12O40 (SiW) and phosphotungstic acid H3PW12O40 (PW). Keggin acids can catalyze the oxidation of 4-carboxybenzaldehyde (4-CBA) and p-tolualdehyde (p-Tol) under homogeneous reaction. Also, for additional studies, we reconnoitered the application of Keggin catalyst in the presence of persulfate (PS) as oxidizing agent. ­­­­­­­­­Our results showed that in the presence of PS and (6 watt)UV light, the most active catalyst among the used Keggin acids is the phosphomolybdic acid (80.9% yield) due to the high oxidative ability of molybdenum . The effects of catalyst concentration, time and oxidant load have been studied. The mechanistic aspects of the reaction also have been discussed.

Rapid Screening of Carboxylic Acids from Waste and Surface Waters by ESI-MS/MS Using Barium Ion Chemistry and On-Line Membrane Sampling.

Negative ion tandem mass spectrometric analysis of aliphatic carboxylic acids often yields only non-diagnostic ([M - H](-)) ions with limited selective fragmentation. However, carboxylates cationized with Ba(2+) have demonstrated efficient dissociation in positive ion mode, providing structurally diagnostic product ions. We report the application of barium adducts followed by collision induced dissociation (CID), to improve selectivity for rapid screening of carboxylic acids in complex aqueous samples. The quantitative MS/MS method presented utilizes common product ions of [M - H + Ba](+) precursor ions. The mechanism of product ion formation is investigated using isotopically labeled standards and a series of structurally related carboxylic acids. The results suggest that hydrogen atoms in the β and γ positions yield common product ions ([BaH](+) and [BaOH](+)). Furthermore, the diagnostic product ion at m/z 196 serves as a qualifying ion for carboxylate species. This methodology has been successfully used in conjunction with condensed phase membrane introduction mass spectrometry (CP-MIMS), with barium acetate added directly to the methanol acceptor phase. The combination enables rapid screening of carboxylic acids directly from acidified water samples (wastewater effluent, spiked natural waters) using a capillary hollow fiber PDMS membrane immersion probe. We have applied this technique for the direct analysis of complex naphthenic acid mixtures spiked into natural surface waters using CP-MIMS. Selectivity at the ionization and tandem mass spectrometry level eliminate isobaric interferences from hydroxylated species present within the samples, which have been observed in negative electrospray ionization.

The formic acid-nitric acid complex: microwave spectrum, structure, and proton transfer.

Rotational spectra are reported for seven isotopologues of the complex HCOOH-HNO3 in a supersonic jet. The system is planar and bound by a pair of hydrogen bonds, much like the more widely studied carboxylic acid dimers. Double proton exchange interconverts the system between a pair of equivalent structures, as revealed by a splitting of the a-type spectrum that disappears when one of the hydrogen bonding protons is replaced by deuterium. The observation of relative intensities that are consistent with nuclear spin statistics in a symmetric and antisymmetric pair of tunneling states provides additional evidence for such a motion. The observed splittings in the pure rotational spectrum are 1-2 orders of magnitude smaller than those recently reported in the pure rotational spectra of several related carboxylic acid dimers. This is a curious difference, although we note that because the observed spectra do not cross the tunneling doublet, the splittings are a measure of the difference in effective rotational constants for the two states, not the tunneling frequency itself. The observed rotational constants have been used to determine an accurate vibrationally averaged structure for the complex. The two hydrogen bond lengths, 1.686(17) Å and 1.813(10) Å for the hydrogen bonds involving the HNO3 and HCOOH protons, respectively, differ by 0.127(27) Å. Likewise, the associated oxygen-oxygen distances determined for the parent species, 2.631 and 2.794 Å, differ by 0.163 Å. These results suggest that the double proton transfer is necessarily accompanied by substantial motion of the heavy atom frame, and thus this system, in principle, provides an excellent prototype for multidimensional tunneling processes. Ab initio calculations of the binding energy and the barrier height are presented. Excellent agreement between the calculated equilibrium structure and the experimental, vibrationally averaged structure suggests that the vibrational wave function is not highly delocalized in the region between the equivalent potential wells. (14)N nuclear quadrupole hyperfine structure is interpreted in terms of the degree to which the HNO3 releases its proton in either of the equivalent potential energy minima.

Using probing compounds to investigate adsorption mechanism of ciprofloxacin on montmorillonite

Ciprofloxacin (CIP) adsorption on montmorillonite was investigated using structurally related probing compounds phenylpiperazine (PP) and fluorochloroquinolone carboxylic acid (FCQCA). Desorption of the equivalent amounts of exchangeable cations accompanying PP and CIP adsorption on montmorillonite suggested that cation exchange was the major adsorption mechanism for the CIP adsorption under acidic to neutral conditions, and the piperazine amine group was responsible for the cation exchange interaction. In contrast, the adsorption of CIP and FCQCA on montmorillonite indicated that hydrogen bonding between the keto carbonyl group and coordinated water in the interlayer of montmorillonite was mainly responsible for the CIP adsorption in alkaline aqueous solution as evidenced by Fourier transform infrared analyses. X-ray diffraction analyses demonstrated that both cation exchange and hydrogen bonding between the keto carbonyl group and coordinated water lead to the intercalation of CIP in montmorillonite.

Radiation processing of thermoplastic starch by blending aromatic additives: Effect of blend composition and radiation parameters

This paper reports on the effects of electron beam (EB) irradiation on poly α-1,4-glucose oligomers (maltodextrins) in the presence of water and of various aromatic additives, as model blends for gaining a better understanding at a molecular level the modifications occurring in amorphous starch–lignin blends submitted to ionizing irradiation for improving the properties of this type of bio-based thermoplastic material. A series of aromatic compounds, namely p-methoxy benzyl alcohol, benzene dimethanol, cinnamyl alcohol and some related carboxylic acids namely cinnamic acid, coumaric acid, and ferulic acid, was thus studied for assessing the ability of each additive to counteract chain scission of the polysaccharide and induce interchain covalent linkages. Gel formation in EB-irradiated blends comprising of maltodextrin was shown to be dependent on three main factors: the type of aromatic additive, presence of glycerol, and irradiation dose. The chain scission versus grafting phenomenon as a function of blend composition and dose were studied using Size Exclusion Chromatography by determining the changes in molecular weight distribution (MWD) from Refractive Index (RI) chromatograms and the presence of aromatic grafts onto the maltodextrin chains from UV chromatograms. The occurrence of crosslinking was quantified by gel fraction measurements allowing for ranking the cross-linking efficiency of the additives. When applying the method to destructurized starch blends, gel formation was also shown to be strongly affected by the moisture content of the sample submitted to irradiation. The results demonstrate the possibility to tune the reactivity of tailored blend for minimizing chain degradation and control the degree of cross-linking.

Identification of carboxylic and organoboronic acids and phenols with a single benzobisoxazole fluorophore

The fluorescence of a single donor–acceptor benzobisoxazole-based cruciform, dissolved in five different solvents, dramatically changes upon exposure to Brønsted and Lewis acids. The changes in emission colors strongly depend on the analyte's structure, and this cruciform can discern among structurally closely related carboxylic (twelve examples) and organoboronic acids (nine examples). In combination with two commercially available phenylboronic acids, this cruciform sensor also distinguishes among substituted phenols (twelve examples).

Preyssler Anion as a Green and Eco-friendly Catalyst for Photocatalytic Oxidation of Aromatic Aldehydes

Photocatalytic oxidation of aromatic aldehydes to related carboxylic acids was investigated with molecular oxygen in the presence of Preyssler anion, with formula [NaP5W30O110]14 −. It was observed that H14[NaP5W30O110] could catalyze the oxidation of aromatic aldehydes by molecular oxygen under homogeneous conditions as well as supported on silica in heterogeneous conditions. Also, for further studies, we have investigated the application of Preyssler catalyst in the presence of hydrogen peroxide as oxidizing agent. Our findings showed that this catalyst is very active in the presence of hydrogen peroxide and UV light. The effects of catalyst concentration, time and loading percentage have been studied.

Degradation of the biocide 4-chloro-3,5-dimethylphenol in aqueous medium with ozone in combination with ultraviolet irradiation: Operating conditions influence and mechanism

Biocides usually persist during municipal sewage treatment and are subsequently distributed into aquatic environments. To explore the capability of advanced oxidation processes for the rapid removal of biocides, we examined the total organic carbon (TOC) reduction of 4-chloro-3,5-dimethylphenol (PCMX) with a combination of UV/O 3. Moreover, the related important parameters, including the mass transfer coefficient and light utilization efficiency, in PCMX degradation were determined. The UV/O 3 experimental results showed a pronounced synergistic effect, leading to the nearly complete elimination of TOC within 75 min. Thus, the effect of operating variables was investigated as a function of pH, ozone dosage, bulk temperature and the initial concentration of PCMX. The efficiency of PCMX mineralization increased with an increase in ozone dose up to 3.1 g h −1, and a decrease in the initial concentration from 250 to 100 mg L −1. The optimal pH value was 4.0, and the preferred bulk temperature was 20 °C on the basis of the influence of temperature on reaction rate and ozone solubility. The major aromatic intermediates identified by gas chromatography/mass spectrometry were 2,6-dimethylbenzene-1,4-diol, 2,6-dimethylbenzo-1,4-quinone, 2,6-bis(hydroxymethyl)benzo-1,4-quinone, and 2,6-dimethylbenzo-1,4-aldehyde. Quantitative determination of related carboxylic acid and inorganic anions was done by ion chromatography. On the basis of the identified reaction products, a possible degradation pathway for the UV/O 3 oxidation of PCMX in aqueous media is proposed.