Symmetrical Anhydrides Research Articles

Facile Cleavage of Activated Ketones: An Access to Thioethers via In Situ Generation of Anhydrides by Pummerer-Type Rearrangement.

Herein, we report an oxygen insertion in activated ketones from simple inorganic carbonates for the synthesis of symmetric aromatic anhydrides. For the first time, Li2CO3 acts as an oxygen source and the in situ generated symmetric aromatic anhydrides undergo Pummerer-type rearrangement to access α-benzoyloxy-thioethers. Attractively, this protocol occurs under metal-, ligand-, and oxidant-free conditions and is compatible with a wide range of substrates. Control experiments reveal the reaction pathway.

Synthesis, Antimicrobial Activities and Molecular Docking Studies of New N-Acylated Derivatives of 5-(2-Phenyl-1,8-naphthyridin-3-yl)-1,3,4-oxadiazol-2-amine

Present study establishes a novel synthetic route of N-acetylated derivatives of 5-(2-phenyl-1,8-naphthyridine-3-yl)-1,3,4-oxadiazole-2-amine (6a-j), which was achieved in four steps with good yields. 2-Amino nicotinaldehyde and ethyl 3-oxo-3-phenylpropanoate on refluxing with triethylamine in ethanol undergoes Friedlander synthesis to furnish ethyl 2-phenyl-1,8-naphthyridine-3-carboxylate, which further converted into 2-phenyl-1,8-naphthyridine-3-carbohydrazide by reacting with hydrazine hydrate upon reflux, followed by cyclization with cyanogen bromide in the presence of water and 1,4-dioxane with sodium bicarbonate to afford 5-(2-phenyl-1,8-naphthyridin-3-yl)-1,3,4-oxadiazol-2-amine (5). Compound 5 was acetylated using numerous symmetrical anhydrides to synthesize novel N-acetylated derivatives (6a-j). The IR, 1H, 13C NMR and mass spectral analysis were used to characterize the structure of synthetic compounds. The synthesized compounds were evaluated for their antimicrobial efficiency against bacteria (S. aureus and E. coli) using ampicillin as a standard reference and against fungi (C. albicans) using fluconazole as a standard reference. Compound 6e exhibited good antibacterial properties while compounds 6c and 6e had shown high antifungal activity, whereas remaining compounds shown moderate to weaker antimicrobial activity. The synthesized derivatives verified their docking strength against Mtb MurB (PDB ID: 5JZX) and showed significant docking activity, however, compound 6f (-10.98 kcal/mol) and compound 6b (-10.52 kcal/mol) had a strong binding affinity compared to the other synthesized compounds.

Palladium‐Catalyzed Synthesis of Carboxylic Acid Anhydrides from Alkenes via in situ Generated Carboxylic Acids

AbstractWe herein present a carbonylative strategy to synthesize carboxylic acid anhydrides from alkenes from in situ generated carboxylic acids. Formic acid (FA) reacts with alkene and CO under catalytic conditions to generate carboxylic acids. With our established palladium‐based catalytic reaction conditions and modulating the alkene:formic acid ratio to at least 2 : 1, acid anhydrides were effectively generated from alkenes. The catalytic process was applied to various alkenes, simple as well as with various functional groups, to give moderate to excellent yields as observed with NMR and upon isolation of the corresponding (linear) amide produced on derivatization. Furthermore, one‐pot derivatization of the reaction mixtures provides direct access to various acyl‐based molecules including phenolic esters, primary amides, thioesters and ketones, which otherwise require special conditions for their synthesis via carbonylation.

SYNTHESIS, BIOLOGICAL EVALUATION AND DOCKING STUDIES OF NEW 5-(4-ISOPROPYL PHENYL)-1,3,4- THIADIAZOL-2-AMINE DERIVATIVES

A straightforward synthetic pathway has been developed to prepare N-acylated derivatives of 5-(4-isopropyl phenyl)-1,3,4-thiadiazol-2-yl)amines 3(a-j) by reacting 5-(4-isopropyl phenyl)-1,3,4-thiadiazol-2-amine (2) with various symmetrical acid anhydrides in pyridine solvent under refluxing conditions with good yields. This study involves simple, easy, cheap, inexpensive, and benign processes. Molecular docking investigations were done using an auto dock and found that 3i, 3h, and 3a had good binding energies with PDB ID: 5JZX. The antibacterial efficacy of compounds 3(a-j) was investigated against S. aureus and E. coli. Among all the compounds 3c, 3h & 3j showed good strength towards gram-positive and compounds 3e, 3i & 3j showed good strength on gram-negative bacteria. Further antifungal activity is done against Candida albicans. Most of the prepared compounds 3(a-j) showed good activity against tested microorganisms.

Response surface methodology based on the Box‐Behnken design for optimizing the synthesis of symmetrical anhydrides from acid chlorides using cerium (III) as a homogeneous catalyst

AbstractHere we report the synthesis of symmetrical carboxylic acid anhydrides from acid chlorides using cerium (III) as a homogeneous catalyst. The optimal experimental conditions (temperature at 40 °C, catalyst loading at 30 mg, 1.5 equivalents of base, and solvent volume at 1 mL) for the preparation of benzoic anhydride2 awere obtained using the Box‐Behnken design in combination with the response‐surface methodology. The analysis of variance showed that the presented quadratic model successfully performed the experimental data with coefficients of determination of R2=0.99. The predicted yield of synthesized anhydride2 aobtained from the RSM under optimal conditions was 98.63 %. A confirmation test of the optimal conditions proved the viability of the model and gave a yield of 97.27 %. Under the optimal conditions, the resulting synthesized anhydrides2 a–gwere obtained with good isolated chemical yields of 60 %<yield<96 %.

An Efficient Light-mediated Protocol for the Direct Amide Bond Formation via a Novel Carboxylic Acid Photoactivation Mode by Pyridine-CBr4.

The direct amide bond formation between a carboxylic acid and an amine still constitutes a challenging reaction for both academia and industry. We demonstrate herein that several pairs of amines (halogen bond acceptors) and organohalogen sources may be used for the photochemical amidation reaction under either UVA or sunlight irradiation. Our studies led to the identification of pyridine-CBr4 as an efficient agent to perform synthesis of amides under LED 370 nm irradiation, avoiding super-stoichiometric quantities. An extended substrate scope was demonstrated, showing that the widely used amino and carboxyl protecting groups are compatible with this photochemical protocol, while a number of industrially interesting products and bioactive compounds were synthesized. Direct infusion-high resolution mass spectrometry studies suggest an unprecedented type of carboxylic acid activation mode upon irradiation, involving the generation of a symmetric anhydride, an active ester with pyridine N-oxide and a mixed anhydride with hypobromous acid.

Light-Mediated Synthesis of Aliphatic Anhydrides by Cu-Catalyzed Carbonylation of Alkyl Halides

Acid anhydrides are valuable in the chemical industry for their role in synthesizing polymers, pharmaceuticals, and other commodities, but their syntheses often involve multiple steps with precious metal catalysts. The simplest anhydride, acetic anhydride, is currently produced by two Rh-catalyzed carbonylation reactions on a bulk scale for its use in synthesizing products ranging from aspirin to cellulose acetate. Here, we report a light-mediated, Cu-catalyzed process for producing aliphatic, symmetric acid anhydrides directly by carbonylation of alkyl (pseudo)halides in a single step without any precious metal additives. The transformation requires only simple Cu salts and abundant bases to generate a heterogeneous Cu0 photocatalyst in situ, maintains high efficiency and selectivity upon scale-up, and operates by a radical mechanism with several beneficial features. This discovery will enable the engineering of bulk processes for producing commodity anhydrides efficiently and sustainably.

Base-Mediated Synthesis of Anhydrides from Activated Amides.

Symmetrical anhydrides were synthesized from activated amides such as N-benzoylsaccharins and N-Boc-protected benzamides. The activated amides reacted with H2O in the presence of 1,4-diazabicyclo[2.2.2]octane (DABCO) at 25 °C to produce the corresponding symmetrical anhydrides in high yields through C-N bond cleavage. In addition, N-benzoylsaccharins reacted with benzoic acid derivatives to generate unsymmetrical anhydrides in high yields.

Synthesis, characterization, biological evaluation and docking studies of novel 5-(2-methyl-1,8-naphthyridin-3-yl)-1,3,4-oxadiazol-2-amine and some of its derivatives using symmetrical anhydrides

The present work demonstrates the novel compounds of 5-(2-methyl-1,8-naphthyridin-3-yl)-1,3,4-oxadiazol-2-amine and its derivatives using symmetrical anhydrides. The synthesized 5-(2-methyl-1,8-naphthyridin-3-yl)-1,3,4-oxadiazol-2-amine and its derivatives were successfully characterized by 1H NMR, FTIR, 13C NMR, and Mass Spectral data. The synthesized compounds of formula 5 and 5(a-j) have been screened for their in-vitro antibacterial and antifungal properties against Staphylococcus aureus and Escherichia coli as bacterial strains and Candida albicans as a fungal strain. The antimicrobial activity was compared using reference compounds by disc diffusion method and the majority of the compounds exhibited significant antimicrobial activity, and some of them were exhibited promising antimicrobial activity. In addition, all the novel compounds have good docking scores.

Synthesis and characterization of novel bio-based polyesters and poly(ester amide)s based on isosorbide and symmetrical cyclic anhydrides

Synthesis and characterization of novel bio-based polyesters and poly(ester amide)s based on isosorbide and symmetrical cyclic anhydrides

A Facile Synthetic Method for Anhydride from Carboxylic Acid with the Promotion of Triphenylphosphine Oxide and Oxaloyl Chloride.

A highly efficient synthesis reaction of carboxylic anhydrides catalyzed by triphenylphosphine oxide is described for the quick synthesis of a range of symmetric carboxylic anhydrides and cyclic anhydrides under mild and neutral conditions with a high yield. The system adopts the strong reactive intermediate Ph3PCl2 as the catalyst of carboxylic acid salt; driven by catalytic reaction, the synthesis takes a relatively short time to complete.

Antimicrobial nanofibrous mats with controllable drug release produced from hydrophobized hyaluronan

Due to their large active surface, high loading efficiency, and tunable dissolution profiles, nanofibrous mats are often cited as promising drug carriers or antimicrobial membranes. Hyaluronic acid has outstanding biocompatibility, but it is hydrophilic. Nanofibrous structures made from hyaluronan dissolve immediately, making them unsuitable for controlled drug release and longer applications. We aimed to prepare a hyaluronan-based antimicrobial nanofibrous material, which would retain its integrity in aqueous environments. Self-supporting nanofibrous mats containing octenidine dihydrochloride or triclosan were produced by electrospinning from hydrophobized hyaluronan modified with a symmetric lauric acid anhydride. The nanofibrous mats required no cross-linking to be stable in PBS for 7 days. The encapsulation efficiency of antiseptics was nearly 100%. Minimal release of octenidine was observed, while up to 30% of triclosan was gradually released in 72 h. The nanofibrous materials exhibited antimicrobial activity, the fibroblast viability was directly dependent on the antiseptic content and its release.

Efficient synthesis of symmetrical anhydrides by cross dehydrogenative coupling of aryl aldehydes over CuFe2O4 nanoparticles

Nano copper ferrite catalyst is prepared and characterized by scanning electron microscopy, energy dispersive X-ray, X-ray diffraction, vibrational sample magnetometry, and Fourier transform infrared. The catalytic activity is probed for cross-dehydrogenative coupling of aromatic aldehydes in the presence of tert-butyl hydroperoxide as the oxidant. This catalytic protocol appears as a simple, rather cheap, clean, and efficient practical strategy for the synthesis of symmetrical anhydrides, with proper efficiency (66%). The catalyst can be easily separated from the reaction mixture by an external magnet and reused several times in subsequent reactions, without any measurable loss of its efficiency.

Photochemical Asymmetric Nickel-Catalyzed Acyl Cross-Coupling.

Photochemical enantioselective nickel‐catalyzed cross‐coupling reactions are difficult to implement. We report a visible‐light‐mediated strategy that successfully couples symmetrical anhydrides and 4‐alkyl dihydropyridines (DHPs) to afford enantioenriched α‐substituted ketones under mild conditions. The chemistry does not require exogenous photocatalysts. It is triggered by the direct excitation of DHPs, which act as a radical source and as a reductant, facilitating the turnover of the chiral catalytic nickel complex.

Photochemical Asymmetric Nickel‐Catalyzed Acyl Cross‐Coupling

AbstractPhotochemical enantioselective nickel‐catalyzed cross‐coupling reactions are difficult to implement. We report a visible‐light‐mediated strategy that successfully couples symmetrical anhydrides and 4‐alkyl dihydropyridines (DHPs) to afford enantioenriched α‐substituted ketones under mild conditions. The chemistry does not require exogenous photocatalysts. It is triggered by the direct excitation of DHPs, which act as a radical source and as a reductant, facilitating the turnover of the chiral catalytic nickel complex.

Synthesis of Symmetric Carboxylic Anhydrides from Aldehydes on a Cu-MOF

Synthesis of Symmetric Carboxylic Anhydrides from Aldehydes on a Cu-MOF

Electrophilic Activation of Carboxylic Anhydrides for Nucleophilic Acylation Reactions

Nucleophilic acylation of symmetrical carboxylic anhydrides has inherited limitation of reaction efficiency along with relatively poor reactivity. Traditionally, one equivalent carboxylic acid is generated during nucleophilic acylation of a symmetrical anhydride, which always limits the yield of final product to 50% or less. This is a major drawback, which discourages the use of anhydrides for laboratory or industrial applications. Electrophilic activation of carboxylic anhydride using methanesulfonyl chloride is found to be an efficient method for nucleophilic acylation, which increases product yield by restricting the formation of corresponding acid as a side product. The developed protocol found to be a mild and high yielding methodology for one-pot nucleophilic acylation of carboxylic anhydrides with several type of N- and S-nucleophiles demonstrating appreciable functional group tolerance.

Cu-MOF: an efficient heterogeneous catalyst for the synthesis of symmetric anhydrides via the C-H bond activation of aldehydes.

In this paper, an efficient and straightforward synthetic approach for the preparation of a number of symmetric carboxylic anhydrides was reported using Cu2(BDC)2(DABCO) as an efficient heterogeneous catalyst via the C–H bond activation of aldehydes with excellent yields and simple work up. This C–H bond activation reaction appears simple and convenient, has a wide substrate scope and makes use of cheap, abundant, and easily available reagents. The Cu-MOF catalyst was recycled and reused four times without any loss of catalytic activity.

TBHP/n-Bu4PBr-Promoted Oxidative Cross-Dehydrogenative Coupling of Aryl Methanols: A Facile Synthesis of Symmetrical Carboxylic Anhydride Derivatives

A transition-metal-free oxidative cross-dehydrogenative coupling reaction has been developed for the preparation of symmetrical carboxylic anhydrides through self-coupling dual C–O bond formations of aryl methanols. In the presence of a catalytic amount of tetrabutylphosphonium bromide (TBPB) as transfer agent and aqueous tert-butyl hydroperoxide (TBHP) as oxidant and reactant, methylene groups of aryl methanols were efficiently oxidized to C=O and coupled with the peroxide oxygen from TBHP to form a diverse array of symmetrical carboxylic anhydride derivatives.

Metal-free oxidative self-coupling of aldehydes or alcohols to symmetric carboxylic anhydrides

Abstract A metal-free synthesis of symmetrical anhydrides has been developed starting from aldehydes, both aliphatic and aromatic or primary benzylic alcohols. The reaction occurs at room temperature and makes use of trichloroisocyanuric acid (TCCA) as an oxidant providing the desired carboxylic anhydrides in satisfactory yields.