Bonds Of Carboxylic Acids Research Articles

Catalyst-Controlled Chemoselective γ-C(sp3)-H Lactonization of Carboxylic Acid: Methyl versus Methylene.

Despite recent advances in ligand-enabled C(sp3)-H functionalization of native substrates, controlling chemoselectivity in the presence of methyl and methylene C(sp3)-H bonds remains a significant challenge. Herein, we report the first example of the Pd(II)-catalyzed chemoselective lactonization of γ-methyl and methylene C(sp3)-H bonds of carboxylic acids. Exclusive chemoselectivity of methyl or methylene γ-lactonization was achieved by using two different classes of Quinoline-Pyridone ligands. The bidentate ligand coordinating with Pd(II) via five-membered chelation favors γ-methyl C-H lactonization, whereas the ligand forming six-membered chelation affords γ-methylene C-H lactonization exclusively. Taking into account our previous findings, we show that the impact of ligand bite angle on chemoselectivity is different for five-membered and six-membered cyclopalladation processes. This method provides simple and versatile access to γ-lactones, including spiro- and fused ring systems. Deuterium incorporation experiments suggest that this observed chemoselectivity arises from both the C-H activation and C-O bond forming steps.

Palladium-Catalyzed Arylation of C(sp2)-H Bonds and C(sp3)-H Bonds with 4-Amino-benzotriazole as the Bidentate Directing Group.

The arylation of C(sp2)-H and C(sp3)-H bonds in carboxylic acids catalyzed by Pd(II) with 4-aminobentriazole as the directing group was investigated. In addition to activation of the C(sp2)-H bond, selective arylation of alkyl carboxylic acids and amino acids in the β position can also be achieved. This strategy involved a 5,5-bicyclic Pd intermediate complex whose structure was determined by X-ray single crystal diffraction analysis. Importantly, the DG (directing group) can be easily removed under mild conditions.

Enantioselective insertion of vinyl diazoacetates into O–H bonds of carboxylic acids

A rhodium and phosphoric acid-catalyzed regio- and enantioselective vinyl carbene insertion into the O–H bonds of carboxylic acids has been achieved.

Catalytic Dehydrative Transformations Mediated by Moisture-Tolerant Zirconocene Triflate

AbstractZirconocene triflate is a powerful moisture-tolerant catalyst for activation of C–O bonds in carboxylic acids and alcohols in the absence of water scavenging techniques. Herein, an overview of the use of this robust metal complex for direct amidation, esterification, and etherification is presented, along with a discussion on mechanistic aspects of the transformations and the catalyst class.

Transition‐Metal‐Catalyzed Remote C(sp3)−H Functionalization Of Carboxylic Acid And Its Derivatives

AbstractCarboxylic acids are ubiquitous functional groups present in many bio‐relevant molecules, including drugs and amino acids. In general, α‐ and β−C(sp3)−H bonds of carboxylic acids are easy to functionalize, contrary to remote (γ‐ and δ) C−H bonds which are difficult due to the distal location of these C−H bonds from the functional group. On the other hand, functionalizing an inert C(sp3)−H bond is another critical challenge in synthetic chemistry due to its lower acidity and reactivity. Nevertheless, the last decade has witnessed tremendous development in remote sp3‐C−H bond functionalization of carboxylic acid and its derivatives. Here, in this review, we have delineated recent progress in remote γ‐ and δ‐C−H bond functionalization of aliphatic carboxylic acids/amino acids and their derivatives. This review is further subdivided based on the type of functionalization reaction. Finally, we have presented some applications of these methodologies, such as total synthesis of hibispeptin A, etc.

S-H…O and O-H…O Hydrogen Bonds-Comparison of Dimers of Thiocarboxylic and Carboxylic Acids.

ωB97-XD/aug-cc-pVTZ calculations were performed on dimers of selected thiocarboxylic acids and on analogous carboxylic acids. The sample of calculated thiocarboxylic acids is an extension of the Cambridge Structural Database search that contains only a few such structures. The Natural Bond Orbital (NBO) method, Symmetry-Adapted Perturbation Theory (SAPT) approach, Non-Covalent Interaction (NCI) method and Quantum Theory of Atoms in Molecules (QTAIM) were applied additionally to analyse interactions in dimers of thiocarboxylic and carboxylic acids. The insights into crystal structures as well as into results of calculations show that the formation of S-H…O hydrogen bonds between molecules of thiocarboxylic acids is steered by the same mechanisms as the formation of much stronger O-H…O hydrogen bonds in carboxylic acids. The intramolecular O-H…O and C-H…S hydrogen bonds occurring in few considered structures are also analysed.

An effective method for bisphosphonate moiety inserting into O–H bond of carboxylic acids by Cu (II) catalyst

In this study we developed a novel copper-catalyzed O–H insertion of tetraethyl diphosphonodiazomethane into carboxylic acids, providing a simple method to link bisphosphonates to compounds containing carboxyl group. Moreover, a novel bone-targeting prodrug of naproxen was synthesized according to this new methodology, and the preliminary evaluation indicated that the prodrug exhibited excellent bone affinity in vitro.

Pd(II)-Catalyzed Arylation and Intramolecular Amidation of γ-C(sp3)-H Bonds: En Route to Arylheteroarylmethane and Pyrrolidone Ring Annulated Furan/Thiophene Scaffolds.

We report the Pd(II)-catalyzed, bidentate directing group (BDG)-assisted arylation and successive arylation/intramolecular amidation of γ-C(sp3)-H bonds. The Pd(II)-catalyzed BDG-assisted C-H activation and functionalization of the β-C(sp3)-H bonds of carboxylic acids are well documented, but only a few reports are available that deal with the BDG-directed functionalization of the γ-C(sp3)-H bonds. Various 3-methylthiophene/furan-2-carboxamides (1a-e) were derived from their corresponding carboxylic acids and bidentate directing groups. These compounds were then used as substrates to investigate the arylation and successive arylation/intramolecular amidation of the γ-C(sp3)-H bonds. The γ-C(sp3)-H arylation arose from the Pd(II)-catalyzed reactions of these compounds with aryl iodides with reaction periods of 4-24 h (except a few reactions which required 36 or 48 h). Notably, these reactions led to the construction of various unsymmetrical diarylmethane scaffolds, such as thiophene/furan-based arylheteroarylmethanes (3-6). Prolonging the reaction period to 48-70 h led to successive γ-C(sp3)-H arylation/intramolecular amidation and the construction of both C-C and C-N bonds. Accordingly, these reactions led to the construction of new classes of pyrrolidone-ring annulated thiophene/furan-based heterocyclic scaffolds (e.g., 4,5-dihydro-6H-thieno[2,3-c]pyrrol-6-ones (8), 4,5-dihydro-6H-furo[2,3-c]pyrrol-6-ones (10), and 1-phenyl-1,2-dihydro-3H-benzo[4,5]thieno[2,3-c]pyrrol-3-ones (12)), and notably, compounds 8, 10, and 12 resemble the skeletons of 3-phenylisoindolin-1-ones.

Asymmetric Catalytic Insertion of α-Diazo Carbonyl Compounds into O–H Bonds of Carboxylic Acids

An efficient enantioselective insertion of α-diazoesters and α-diazoketones into O–H bonds of carboxylic acids was realized by the use of Rh2(OAc)4 and a chiral guanidine. Optically active α-acyloxy carbonyl compounds were generated under mild reaction conditions in high yields (up to 99%) and good enantioselectivities (up to 97.5:2.5 er).

A direct route from acids to alcohols

Catalysis Making alcohols via hydrogen addition to C=O bonds is among the most widely applied reactions in chemistry. The transformation has also garnered renewed interest for generating commodity chemicals from biomass. Korstanje et al. now show that a cobalt compound can catalyze hydrogenation of the C=O bonds in carboxylic acids. These constitute a particularly challenging substrate class, given the propensity of many other catalysts to degrade under acidic conditions. The cobalt catalyst tolerates a versatile substrate range, and the Earth abundance of the metal bodes well for long-term utility. Science , this issue p. [298][1] [1]: /lookup/doi/10.1126/science.aaa8938

Fabrication of molecularly imprinted hybrid monoliths via a room temperature ionic liquid‐mediated nonhydrolytic sol–gel route for chiral separation of zolmitriptan by capillary electrochromatography

A room temperature ionic liquid (RTIL)-mediated nonhydrolytic sol-gel (NHSG) protocol was explored for the fabrication of new molecularly imprinted silica-based hybrid monoliths for chiral separation of a basic template zolmitriptan by CEC. The RTIL-mediated NHSG protocol involved free-radical copolymerization and NHSG process. Three carboxylic acids (trifluoromethyl acrylic acid, cinnamic acid, and methacrylic acid (MAA)) were examined as both the functional monomers and the catalysts for the NHSG condensation of methacryloxypropyltrimethoxysilane (MPTMS) to form silica-based framework. RTIL was incorporated to reduce gel shrinkage and also to act as the pore template. The effects of carboxylic acids and RTIL on the performance of the silica-based hybrid molecularly imprinted polymer (MIP) monoliths were investigated in detail to realize excellent chiral recognition and to give new insights into the mechanism of the RTIL-mediated NHSG strategy. Excellent chiral separation of (R)/(S)-zolmitriptan was achieved when the molar ratio of MAA to MPTMS was 1:4 and 1:2 with RTIL involved. The synergism of the free-radical copolymerization of the C=C bond of carboxylic acids and MPTMS with the NHSG condensation of MPTMS catalyzed by the carboxylic acids was demonstrated. The incorporation of RTIL increased porosity, and hence improved selectivity of the prepared hybrid monoliths.

Energetics and dynamics of H bonds in carboxylic acids studied by resonant photoacoustic spectroscopy

Energetics and dynamics of H bonds in carboxylic acids studied by resonant photoacoustic spectroscopy

Study of Hydrogen Bonding in Carboxylic Acids by the MNDO/M Method

The semiempirical methods MNDO/M, AM1 and PM3 were applied to the study of hydrogen bonds in carboxylic acids. The calculated hydrogen bond lengths and enthalpies of dimerization were compared with experimental data. The AM1 method fails to properly describe systems with strong hydrogen bonds. The PM3 method predicts the hydrogen bond lengths correctly but underestimates systematically the enthalpies of dimerization. MNDO/M appears to be a promising method for the treatment of association of carboxylic acids.

Dynamics of hydrogen bonds in carboxylic acids

The double-proton exchange in carboxylic acids has been studied for a polycrystalline sample of ring-deuterated terephthalic acid (TA), HOOC-C6Da-COOH' and for both single-crystal and polycrystalline samples of acetylene dicarboxylic acid (ADA), HOOC-C2-COOH, by incoherent neutron scattering. For temperatures above 100K the observed energy spectra reveal quasielastic contributions which indicate that the disorder of the hydrogen-bonded dimeric units is of dynamic nature involving a translational jump across the hydrogen bonds. The data have been analysed in terms of a two-site jump model. Jump vectors, relaxation rates and population factors within the asymmetric double-minimum potential have been derived.

Dynamics of hydrogen bonds in carboxylic acids

The double-proton exchange in carboxylic acids has been studied for a polycrystalline sample of ring-deuterated terephthalic acid (TA), HOOC-C6Da-COOH' and for both single-crystal and polycrystalline samples of acetylene dicarboxylic acid (ADA), HOOC-C2-COOH, by incoherent neutron scattering. For temperatures above 100K the observed energy spectra reveal quasielastic contributions which indicate that the disorder of the hydrogen-bonded dimeric units is of dynamic nature involving a translational jump across the hydrogen bonds. The data have been analysed in terms of a two-site jump model. Jump vectors, relaxation rates and population factors within the asymmetric double-minimum potential have been derived.

The Formation of Amino Acids by the Reactions of Singlet NH with Several Carboxylic Acids

Abstract The photolysis of hydrogen azide was studied in liquid acetic acid, propionic acid, and isobutyric acid at room temperature. The formation of amino acids was confirmed by the color reactions with ninhydrin and with chromotropic acid and by the NMR spectra. From the propionic acid, α- and β-alanine were formed in the ratio of 1.5. In the case of isobutyric acid, α- and β-aminoisobutyric acids were formed in the ratio of about 5. These results are explained by the insertion reaction of NH(a1Δ) into the C–H bonds of carboxylic acids.