Showing papers on "Carboxylic acid published in 2022"

A Unified Approach to Decarboxylative Halogenation of (Hetero)aryl Carboxylic Acids.

Abstract: Aryl halides are a fundamental motif in synthetic chemistry, playing a critical role in metal-mediated cross-coupling reactions and serving as important scaffolds in drug discovery. Although thermal decarboxylative functionalization of aryl carboxylic acids has been extensively explored, the scope of existing halodecarboxylation methods remains limited, and there currently exists no unified strategy that provides access to any type of aryl halide from an aryl carboxylic acid precursor. Herein, we report a general catalytic method for direct decarboxylative halogenation of (hetero)aryl carboxylic acids via ligand-to-metal charge transfer. This strategy accommodates an exceptionally broad scope of substrates. We leverage an aryl radical intermediate toward divergent functionalization pathways: (1) atom transfer to access bromo- or iodo(hetero)arenes or (2) radical capture by copper and subsequent reductive elimination to generate chloro- or fluoro(hetero)arenes. The proposed ligand-to-metal charge transfer mechanism is supported through an array of spectroscopic studies.

Oleic acid/oleylamine ligand pair: a versatile combination in the synthesis of colloidal nanoparticles.

Abstract: A variety of colloidal chemical approaches has been developed in the last few decades for the controlled synthesis of nanostructured materials in either water or organic solvents. Besides the precursors, the solvents, reducing agents, and the choice of surfactants are crucial for tuning the composition, morphology and other properties of the resulting nanoparticles. The ligands employed include thiols, amines, carboxylic acids, phosphines and phosphine oxides. Generally, adding a single ligand to the reaction mixture is not always adequate to yield the desired features. In this review, we discuss in detail the role of the oleic acid/oleylamine ligand pair in the chemical synthesis of nanoparticles. The combined use of these ligands belonging to two different categories of molecules aims to control the size and shape of nanoparticles and prevent their aggregation, not only during their synthesis but also after their dispersion in a carrier solvent. We show how the different binding strengths of these two molecules and their distinct binding modes on specific facets affect the reaction kinetics toward the production of nanostructures with tailored characteristics. Additional functions, such as the reducing function, are also noted, especially for oleylamine. Sometimes, the carboxylic acid will react with the alkylamine to form an acid-base complex, which may serve as a binary capping agent and reductant; however, its reducing capacity may range from lower to much lower than that of oleylamine. The types of nanoparticles synthesized in the simultaneous presence of oleic acid and oleylamine and discussed herein include metal oxides, metal chalcogenides, metals, bimetallic structures, perovskites, upconversion particles and rare earth-based materials. Diverse morphologies, ranging from spherical nanoparticles to anisotropic, core-shell and hetero-structured configurations are presented. Finally, the relation between tuning the resulting surface and volume nanoparticle properties and the relevant applications is highlighted.

Carbene and photocatalyst-catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles to form ketones

Abstract: The carbene and photocatalyst co-catalyzed radical coupling of acyl electrophile and a radical precursor is emerging as attractive method for ketone synthesis. However, previous reports mainly limited to prefunctionalized radical precursors and two-component coupling. Herein, an N-heterocyclic carbene and photocatalyst catalyzed decarboxylative radical coupling of carboxylic acids and acyl imidazoles is disclosed, in which the carboxylic acids are directly used as radical precursors. The acyl imidazoles could also be generated in situ by reaction of a carboxylic acid with CDI thus furnishing a formally decarboxylative coupling of two carboxylic acids. In addition, the reaction is successfully extended to three-component coupling by using alkene as a third coupling partner via a radical relay process. The mild conditions, operational simplicity, and use of carboxylic acids as the reacting partners make our method a powerful strategy for construction of complex ketones from readily available starting materials, and late-stage modification of natural products and medicines.

Collaborative Electrochemical Oxidation of the Alcohol and Aldehyde Groups of 5-Hydroxymethylfurfural by NiOOH and Cu(OH)2 for Superior 2,5-Furandicarboxylic Acid Production

Abstract: Electrochemical alcohol oxidation is considered a promising alternative to the oxygen evolution reaction due to the production of high-value products and early onset potential. Herein, we analyze the different reactivities of NiOOH and Cu(OH)2 toward the electrochemical oxidation of alcohol and aldehyde on the furan ring and utilize their characteristics synergistically to enhance the performance of 5-hydroxymethylfurfural (HMF) to 2,5-furandicarboxylic acid (FDCA) conversion. We discovered that Cu(OH)2 has higher reactivity for the oxidation of aldehyde to carboxylic acid than NiOOH, while NiOOH exhibited excellent reactivity toward the oxidation of alcohol to aldehyde. Furthermore, NiOOH–Cu(OH)2 mixed electrodes showed higher activity and faster conversion of HMF to FDCA than individual NiOOH or Cu(OH)2 electrodes. The alcohol oxidation of HMF is initiated by NiOOH, and Cu(OH)2 quickly converts the remaining aldehydes to carboxylic acids at the NiOOH/Cu(OH)2 interface. Further enhancement of the HMF oxidation kinetics of NiOOH/Cu(OH)2 was achieved by preparing a nanofoam structure comprising nanoscale pores and nanodendritic frames, showing instantaneous conversion to FDCA without producing unreacted intermediates.

Effect of Water on a Hydrophobic Deep Eutectic Solvent

Abstract: Deep eutectic solvents (DESs) formed by hydrogen bond donors and acceptors are a promising new class of solvents. Both hydrophilic and hydrophobic binary DESs readily absorb water, making them ternary mixtures, and a small water content is always inevitable under ambient conditions. We present a thorough study of a typical hydrophobic DES formed by a 1:2 mole ratio of tetrabutyl ammonium chloride and decanoic acid, focusing on the effects of a low water content caused by absorbed water vapor, using multinuclear NMR techniques, molecular modeling, and several other physicochemical techniques. Already very low water contents cause dynamic nanoscale phase segregation, reduce solvent viscosity and fragility, increase self-diffusion coefficients and conductivity, and enhance local dynamics. Water interferes with the hydrogen-bonding network between the chloride ions and carboxylic acid groups by solvating them, which enhances carboxylic acid self-correlation and ion pair formation between tetrabutyl ammonium and chloride. Simulations show that the component molar ratio can be varied, with an effect on the internal structure. The water-induced changes in the physical properties are beneficial for most prospective applications but water creates an acidic aqueous nanophase with a high halide ion concentration, which may have chemically adverse effects.

Deoxygenative Functionalizations of Aldehydes, Ketones and Carboxylic Acids

Abstract: The simple and efficient conversion of carbonyl compounds into functionalized alkanes via deoxygenation is highly enabling in chemical synthesis. This Review covers the recent methodology development in carbonyl and carboxyl deoxygenative functionalizations, highlighting some representative and significant contributions in this field. These advances are categorized based on the reactivity patterns of some oxygenated feedstock compounds, including aldehydes, ketones and carboxylic acids. Four types of reactive intermediates arising from aldehydes and ketones during the deoxygenation, namely, bis-electrophiles, carbenoids, bis-nucleophiles and alkyl radical equivalents, are presented, while the carboxylic acids mainly behave as tris-electrophiles when deoxygenated. In each subcategory, selected examples are organized according to the type of bond formation and discussed from a generalized mechanistic perspective.

Aliphatic Sulfonyl Fluoride Synthesis via Reductive Decarboxylative Fluorosulfonylation of Aliphatic Carboxylic Acids NHPI Esters

Abstract: Based on radical sulfur dioxide insertion and fluorination strategy, we have developed an efficient method for aliphatic sulfonyl fluoride synthesis from abundant carboxylic acid, reductant, sulfur dioxide surrogate and electrophilic...

Carboxylic Acids as Adaptive Functional Groups in Metallaphotoredox Catalysis.

Abstract: ConspectusThe development of palladium-catalyzed cross-coupling methods for the activation of C(sp2)-Br bonds facilitated access to arene-rich molecules, enabling a concomitant increase in the prevalence of this structural motif in drug molecules in recent decades. Today, there is a growing appreciation of the value of incorporating saturated C(sp3)-rich scaffolds into pharmaceutically active molecules as a means to achieve improved solubility and physiological stability, providing the impetus to develop new coupling strategies to access these challenging motifs in the most straightforward way possible. As an alternative to classical two-electron chemistry, redox chemistry can enable access to elusive transformations, most recently, by interfacing abundant first-row transition-metal catalysis with photoredox catalysis. As such, the functionalization of ubiquitous and versatile functional handles such as (aliphatic) carboxylic acids via metallaphotoredox catalysis has emerged as a valuable field of research over the past eight years.In this Account, we will outline recent progress in the development of methodologies that employ aliphatic and (hetero)aromatic carboxylic acids as adaptive functional groups. Whereas recent decarboxylative functionalization methodologies often necessitate preactivated aliphatic carboxylic acids in the form of redox-active esters or as ligands for hypervalent iodine reagents, methods that enable the direct use of the native carboxylic acid functionality are highly desired and have been accomplished through metallaphotoredox protocols. As such, we found that bench-stable aliphatic carboxylic acids can undergo diverse transformations, such as alkylation, arylation, amination, and trifluoromethylation, by leveraging metallaphotoredox catalysis with prevalent first-row transition metals such as nickel and copper. Likewise, abundant aryl carboxylic acids are now able to undergo halogenation and borylation, enabling new entry points for traditional, primarily palladium- or copper-catalyzed cross-coupling strategies. Given the breadth of the functional group tolerance of the employed reaction conditions, the late-stage functionalization of abundant carboxylic acids toward desired targets has become a standard tool in reaction design, enabling the synthesis of various diversified drug molecules. The rapid rise of this field has positively inspired pharmaceutical discovery and will be further accelerated by novel reaction development. The achievement of generality through reaction optimization campaigns allows for future breakthroughs that can render protocols more reliable and applicable for industry. This article is intended to highlight, in particular, (i) the employment of aliphatic and (hetero)aryl carboxylic acids as powerful late-stage adaptive functional handles in drug discovery and (ii) the need for the further development of still-elusive and selective transformations.We strongly believe that access to native functionalities such as carboxylic acids as adaptive handles will further inspire researchers across the world to investigate new methodologies for complex molecular targets.

Coumarins effectively inhibit bacterial α-carbonic anhydrases

Abstract: Abstract Coumarins are known to act as prodrug inhibitors of mammalian α-carbonic anhydrases (CAs, EC 4.2.1.1) but they were not yet investigated for the inhibition of bacterial α-CAs. Here we demonstrate that such enzymes from the bacterial pathogens Neisseria gonorrhoeae (NgCAα) and Vibrio cholerae (VchCAα) are inhibited by a panel of simple coumarins incorporating hydroxyl, amino, ketone or carboxylic acid ester moieties in various positions of the ring system. The nature and the position of the substituents in the coumarin ring were the factors which strongly influenced inhibitory efficacy. NgCAα was inhibited with KIs in the range of 28.6–469.5 µM, whereas VchCAα with KIs in the range of 39.8–438.7 µM. The two human (h)CA isoforms included for comparison reason in the study, hCA I and II, were less prone to inhibition by these compounds, with KIs of 137–948.9 µM for hCA I and of 296.5–961.2 µM for hCA II, respectively. These findings are relevant for discovering coumarin bacterial CA inhibitors with selectivity for the bacterial over human isoform, with potential applications as novel antibacterial agents.

Electrochemical determination of Pb2+ and Cd2+ with a poly(pyrrole-1-carboxylic acid) modified electrode

Abstract: A pencil graphite electrode (PGE) was modified by the electropolymerization of pyrrole-1-carboxylic acid (Py-CO2) to form a sensing film of poly(pyrrole-1-carboxylic acid) (PPy-CO2) for the sensitive determination of Pb2+ and Cd2+ by differential pulse anodic stripping voltammetry (DPASV). The porous structure of the PPy-CO2 film uniformly distributes a carboxylate group throughout the coating to selectively coordinate and preconcentrate metal ions. The polymer film was characterized by cyclic voltammetry (CV), scanning electron microscopy (SEM), and energy dispersive X-ray (EDS) and Fourier transform infrared (FTIR) spectroscopy. Under the optimized conditions (analyte solution pH: 6.0, extraction time: 15 min, reduction potential: −1.1 V and reduction time: 160 s), a linear relationship between peak current and metal concentration was obtained from 0.1 to 1 nM for Pb2+ and Cd2+ with detection limits of 0.018 and 0.023 nM, respectively. Simultaneous analysis of Pb2+ and Cd2+ was performed in the presence of the possible interfering ions Cr3+, Bi3+, Cu2+, Fe2+, Zn2+ and Co2+ and in complex matrices. The performance of the PPy-CO2@PGE demonstrated excellent intra-day repeatability, long-term reproducibility over a seven-week period and was utilized for the determination of Pb2+ and Cd2+ in a variety of natural water samples with the results independently verified by inductively coupled plasma-mass spectrometry.

Design and synthesis of benzothiazole-based SLC-0111 analogues as new inhibitors for the cancer-associated carbonic anhydrase isoforms IX and XII

Abstract: Abstract In this work, different series of benzothiazole-based sulphonamides 8a-c, 10, 12, 16a-b and carboxylic acids 14a-c were developed as novel SLC-0111 analogues with the goal of generating potent carbonic anhydrase (CA) inhibitors. The adopted strategy involved replacing the 4-fluorophenyl tail in SLC-0111 with a benzothiazole motif that attached to the ureido linker to produce compounds 8c and its regioisomers 8a-b. In addition, the ureido spacer was elongated by methylene or ethylene groups to afford the counterparts 10 and 12. In turn, the primary sulfamoyl zinc binding group (ZBG) was either substituted or replaced by carboxylic acid functionality in order to provide the secondary sulphonamide-based SLC-0111 analogues 16a-b, and the carboxylic acid derivatives 14a-c, respectively. All compounds (8a-c, 10, 12, 14a-c and 16a-b) were tested for their ability to inhibit CA isoforms CA I, II, IX and XII. Additionally, the in vitro anticancer properties of the developed CAIs were evaluated.

Fullerphene Nanosheets: A Bottom‐Up 2D Material for Single‐Carbon‐Atom‐Level Molecular Discrimination

Abstract: Ultrathin 2D nanoporous materials offer enhanced sensitivity and high spatial resolution in sensing applications making them important for the selective discrimination of guest molecules. Here bottom‐up fabrication is reported of a novel molecularly‐thin nitrogen‐doped 2D fullerphene. Thermal annealing at 700 °C of a bottom‐up assembled fullerene C60‐ethylenediamine (EDA) thin film results in formation of a nitrogen‐doped ultrathin carbon film, fullerphene, which exhibits a hierarchically micro/mesoporous structure at its surfaces. N‐doping of fullerphene is dominated by pyrrolic and quaternary nitrogen atoms, which allow selective and repetitive adsorption and desorption of low‐molecular‐weight carboxylic acid vapors through noncovalent interactions. The large surface area (655.2 m2 g–1) and pore volume (0.659 cc g–1) offered by the hierarchical micro/mesoporous architecture leads to superior sensitivity of fullerphene to formic acid over acetic acid in the vapor phase demonstrating that novel 2D fullerphene provides an attractive platform for the discrimination of carboxylic acids at the single‐carbon‐atom level.

Nickel‐Catalyzed Reductive Acylation of Carboxylic Acids with Alkyl Halides and N‐Hydroxyphthalimide Esters Enabled by Electrochemical Process

Abstract: A sustainable Ni-catalyzed reductive acylation reaction of carboxylic acids via an electrochemical pathway is presented, affording a variety of ketones as major products. The reaction proceeds at ambient temperature using unactivated alkyl halides and N-hydroxyphthalimide (NHP) esters as coupling partners, which exhibits several synthetic advantages, including mild conditions and convenience of amplification (58% yield for 6 mmol scale reaction).

Abraham Solvation Parameter Model: Examination of Possible Intramolecular Hydrogen-Bonding Using Calculated Solute Descriptors

Abstract: Published solubility data for 4,5-dihydroxyanthraquinone-2-carboxylic acid dissolved in several organic solvents of varying polarity and hydrogen-bonding character are used to calculate the Abraham model solute descriptors. Calculated descriptor values suggest that 4,5-dihydroxyanthraquinone-2-carboxylic acid engages in intramolecular hydrogen formation between the two phenolic hydrogens and the proton acceptor sites (the lone electron pairs) on the neighboring quinone oxygen atom. Our study further shows that existing group contribution and machine learning methods provide rather poor estimates of the experimental-based solute descriptors of 4,5-dihydroxyanthraquinone-2-carboxylic acid, in part because the estimation methods to not account for the likely intramolecular hydrogen-bonds. The predictive aspect of the Abraham model is illustrated by predicting the solubility of 4,5-dihydroxyanthraquinone-2-carboxylic acid in 28 additional organic mono-solvents for which experimental data does not exist.

Pd-catalysed C–H functionalisation of free carboxylic acids

Abstract: Pd-catalysed C–H functionalisation of free carboxylic acids has drawn significant attention over the last few years due to the predominance of carboxylic acid moieties in pharmaceuticals and agrochemicals. But their coordinating ability was overlooked and masked by exogenous directing groups for a long time. Even other crucial roles of carboxylic acids as additives and steric inducers that directly influence the mode of a reaction have been widely neglected. This review aims to embrace all of the diverse aspects of carboxylic acids except additive and steric effects by concisely and systematically describing their versatile role in Pd-catalysed proximal and distal C–H activation reactions that could be implemented in the pharmaceutical and agrochemical industries. In addition, the mechanistic perspectives along with several recent strategies developed in the last few years discussed here will serve as educational resources for future research.

Fixation of carbon dioxide to aryl/aromatic carboxylic acids

Abstract: Carbon dioxide (CO 2 ) is a major greenhouse gas and its emission has continuously increased due to anthropogenic activities. The copious amount of CO 2 is available at present and considered as one of the easily reachable carbon source on earth. The consumption of non-renewable resources or fossil fuels leads to the serious increment of CO 2 concentration in the atmosphere. Discovering green and sustainable energy assets and formulating an effectual approach for utilization of CO 2 by sequestration are inevitably prerequisite. An exceptionally judicious technology/method would be necessary for less emission and spot capturing process of anthropogenic CO 2 emanation. The capture and conversion of CO 2 to value added products (chemicals, pharmaceuticals compounds, and materials) offers a win-win situation to diminish both the CO 2 level on the earth as well as the effective utilization of carbon sources. Among several commodity chemicals, the carboxylations of CO 2 to aromatic/aryl carboxylic acids are always attractive as these are the vital compounds for the synthesis of several biologically active molecules, polymers and natural products. With keeping in mind the CO 2 capture and its sequestration to the various aromatic/aryl carboxylic acids, in this exhaustive review we have depicted various important contents like base mediated catalyst, metal based catalyst, electrochemically, photochemically, enzymatically, and new emerging field of porous catalyst such as metal organic frameworks (MOFs) in a homogeneous and heterogeneous manner. Furthermore, each content is explicitly elaborated with various catalytic system along with the mechanism, based on the thorough literature survey. The fixation of CO 2 into the C-H bond of various aryl/aromatic substrates promoted by catalyst for the synthesis of aryl/aromatic carboxylic acids. • Review is based on the conversion of CO 2 to aryl/aromatic carboxylic acids. • Catalysts like base medium, Grignard, Lewis acid and metal ions are evaluated. • Methods like photochemical, electrochemical and enzymatic are enlightened. • The role of new emerging porous catalyst, MOFs are also discussed. • The mechanisms of catalytic cycles are critically presented.

Nickel-Mediated Synthesis of Non-Anomeric C-Acyl Glycosides through Electron Donor-Acceptor Complex Photoactivation.

Abstract: The preparation of nonanomeric C-acyl-saccharides has been developed from two different carboxylic acid feedstocks. This transformation is driven by the synergistic interaction of an electron donor-acceptor complex and Ni catalysis. Primary-, secondary-, and tertiary redox-active esters are incorporated as coupling partners onto preactivated pyranosyl- and furanosyl acids, preserving their stereochemical integrity. The reaction occurs under mild conditions, without stoichiometric metal reductants or exogenous catalysts, using commercially available Hantzsch ester as the organic photoreductant.

Photouncaging of Carboxylic Acids from Cyanine Dyes with Near‐Infrared Light

Abstract: Abstract Near‐infrared light (NIR; 650–900 nm) offers unparalleled advantages as a biocompatible stimulus. The development of photocages that operate in this region represents a fundamental challenge due to the low energy of the excitation light. Herein, we repurpose cyanine dyes into photocages that are available on a multigram scale in three steps and efficiently release carboxylic acids in aqueous media upon irradiation with NIR light up to 820 nm. The photouncaging process is examined using several techniques, providing evidence that it proceeds via photooxidative pathway. We demonstrate the practical utility in live HeLa cells by delivery and release of the carboxylic acid cargo, that was otherwise not uptaken by cells in its free form. In combination with modularity of the cyanine scaffold, the realization of these accessible photocages will fully unleash the potential of the emerging field of NIR‐photoactivation and facilitate its widespread adoption outside the photochemistry community.