Aryl Esters Research Articles

Unveiling thecb‐typeIntramolecular [3+2] Cycloaddition Reactions of Fluorinated Azomethine Ylides to Ester Carbonyls with a Molecular Electron Density Theory Perspective

AbstractThe carbenoid‐type (cb‐type) intramolecular [3+2] cycloaddition (IM32CA) reactions of four fluorinated azomethine ylides (AYs) bearing an ester carbonyl substituent have been studied from the molecular electron density theory (MEDT) perspective. The presence of two fluorine atoms in these species changes thepseudodiradicalstructure of the simplest AY to that of a carbenoid one, according to thecb‐typemolecular reactivity of these IM32CA reactions. These IM32CA reactions present low activation energies, lesser than 3.0 kcal ⋅ mol−1, and a strongly exothermic character, more than −34.0 kcal ⋅ mol−1, showing a complete chemo‐ and regioselectivity. The presence of the electron‐withdrawing −CN group at the aryl ester framework increases the global electron density transfer (GEDT) at the transition state structure (TS), which fluxes from the nucleophilic AY moiety to the electrophilic carbonyl ester, diminishing the activation energy by 2 kcal ⋅ mol−1relative to that of the phenyl substituent. Electron Localization Function and Atom‐in‐Molecules topological analyses of the most favorable TSs show the early character of thesecb‐typeIM32CA reactions. The present MEDT study makes it possible to establish that the carbenoid structure of these fluorinated AYs together with their supernucleophilic character are responsible for the high reactivity and selectivities shown by these three‐atom‐components participating incb‐type32CA reactions towards carbonyl compounds.

Isothiourea-Catalyzed Enantioselective Michael Addition of Malonates to α,β-Unsaturated Aryl Esters

An enantioselective Michael addition of malonates to α,β-unsaturated para-nitrophenyl esters was achieved using the Lewis basic isothiourea HyperBTM, giving excellent levels of product enantioselectivity (up to >99:1 enantiomeric ratio) in good yields and with complete regioselectivity (>20:1 regioselectivity ratio) in the presence of alternative (phenyl ketone and ethyl ester) Michael acceptors. Density functional theory calculations indicate that N-acylation is rate-limiting. This constitutes a rare example of a highly enantioselective addition of simple, readily available malonates to α,β-unsaturated esters.

Hydroxy- and Amino-Phosphonates and -Bisphosphonates: Synthetic Methods and Their Biological Applications.

Phosphonates and bisphosphonates are stable analogs of phosphates and pyrophosphates that are characterized by one and two carbon–phosphorus bonds, respectively. Among the various phosphonates and bisphosphonates, hydroxy and amino substitutes are of interest as effective in medicinal and industrial chemistry. For example, hydroxy bisphosphonates have proven to be effective for the prevention of bone loss, especially in osteoporotic disease. On the other hand, different substitutions on the carbon atom connected to phosphorus have led to the synthesis of many different hydroxy- and amino-phosphonates and -bisphosphonates, each with its distinct physical, chemical, biological, therapeutic, and toxicological characteristics. Dialkyl or aryl esters of phosphonate and bisphosphonate compounds undergo the hydrolysis process readily and gave valuable materials with wide applications in pharmaceutical and agriculture. This review aims to demonstrate the ongoing preparation of various classes of hydroxy- and amino-phosphonates and -bisphosphonates. Furthermore, the current review summarizes and comprehensively describes articles on the biological applications of hydroxyl- and amino-phosphonates and -bisphosphonates from 2015 until today.

Electrochemical, EPR, and quantum chemical study of reductive cleavage of cone‐Calix[4]arene nosylates – New electrosynthetic approach

AbstractThe mechanism of electrochemical reduction of a series of six cone‐calix[4]arene‐bis‐nosylates (4‐nitrophenylsulfonate aryl esters) was investigated on mercury electrodes using DC‐polarography and cyclic voltammetry (CV) combined with in situ electron paramagnetic resonance (EPR)‐spectroelectrochemistry in aprotic dimethylformamide. Model compounds – expected fragments and products ‐ were studied for comparison. The experimental results are supported by quantum chemical calculations. All calix[4]arene‐bis‐nosylates are reduced in a first reversible step to bis‐(radical anion) by two simultaneous one‐electron transfers. Each of the two electrons is unpaired and separately localized on two nosylate groups.In the second reduction step next 2×2 electrons are transferred and both sulfonate ester groups are cleaved to two 4‐nitro‐benzenesulfinate ions and a calixarene bis‐phenolate (95%). This electroreductive generation of arylsulfinate anions is a significant finding from the electrosynthetic point of view. Activated arylsulfinates, the synthesis of which is generally difficult, can be easily prepared by electrochemical reduction of the nosyl esters.

Dearomatization of Heteroarenium Salts with ArBpin Reagents. Application to the Total Synthesis of a Nuphar Alkaloid.

Rhodium-catalyzed enantioselective addition of aryl and heteroaryl boron pinacol esters to pyridinium and quinolinium salts is developed for the synthesis of enantioenrichred dihydroheteroarenes. The methodology has enabled the synthesis of 2-heteroaryl-substituted dihydropyridines in high yield and ee, which provided efficient synthetic access to a nuphar alkaloid.

Pd-Catalyzed Difluoromethylations of Aryl Boronic Acids, Halides, and Pseudohalides with ICF2 H Generated ex Situ.

An expedient ex‐situ generation of difluoroiodomethane (DFIM) and its immediate use in a Pd‐catalyzed difluoromethylation of aryl boronic acids and ester derivatives in a two‐chamber reactor is reported. Heating a solution of bromodifluoroacetic acid with sodium iodide in sulfolane proved to be effective for the generation of near stoichiometric amounts of DFIM for the ensuing catalytic coupling step. A two‐step difluoromethylation of aryl (pseudo)halides with tetrahydroxydiboron as a low‐cost reducing agent, both promoted by Pd catalysis, proved effective to install this fluorine‐containing C1 group onto several pharmaceutically relevant molecules. Finally, the method proved adaptable to deuterium incorporation by simply adding D2O to the DFIM‐generating chamber.

Visible‐Light‐Promoted Metal‐Free Photocatalytic Direct Aromatic C−H Oxygenation

AbstractAromatic C−O bond is ubiquitous in natural product and pharmaceuticals, and their formation have significant importance in organic synthesis. A mild atom‐economic visible‐light photocatalytic approach has been developed for single‐step synthesis of diverse aryl alcohols, ethers and esters through direct C−H functionalization of aromatic ring at ambient condition. This approach uses DDQ as photocatalyst and TBN as co‐catalyst to facilitate the substitution of aromatic C−H by neutral nucleophile oxygen of water, alcohols and carboxylic acids and it uses aerobic oxygen as the terminal oxidant to produce water as the only by‐product.

Sulfur-promoted, one-pot, and metal-free conversion of aromatic aldehydes to nitriles using an inorganic ammonium salt as the nitrogen source

A simple protocol for the sulfur-promoted conversion of aromatic aldehydes to aromatic nitriles has been developed. This strategy enables the one-pot conversion of inexpensive and readily available aromatic aldehydes into highly valuable aromatic nitriles using a cheap inorganic ammonium salt as the nitrogen source in the absence of metals. Significantly, a broad scope of substrates was explored using this strategy, and various groups, including alkyl, alkoxyl, alkylthiol, hydroxyl, amino, aryl, alkenyl, cyano, carboxyl, and borate ester groups were tolerated, and good to excellent yields were achieved in most cases. Additionally, polycyclic aromatic aldehydes and heteroaromatic aldehydes also could be converted to the corre-sponding nitriles with satisfactory yields. This method can be utilized as a powerful tool for the cyanation of complex molecules.

Mesoporous Carbon-Supported Pd Nanoparticles in the Metallic State-Catalyzed Acylation of Amides with Aryl Esters via C-O Activation.

Carbon, an abundant, inexpensive, and nonmetallic material, is an inimitable support in heterogeneous catalysis, and variable carbonaceous materials have been utilized to support metal nanoparticle catalysts. We developed an efficient and stable heterogeneous catalyst with highly dispersed metallic palladium nanoparticles embedded in an ordered pore channel of mesoporous carbon and first applied the catalyst to construct imides from amides using aryl esters as an acylation reagent via C–O activation. The catalyst represents excellent catalytic performance and could be reused and recycled five times without any significant decrease in activity. The heterogeneous nature of metallic state palladium was proven to be the active center in the acylation reaction.

A PON for All Seasons: Comparing Paraoxonase Enzyme Substrates, Activity and Action including the Role of PON3 in Health and Disease.

Paraoxonases (PONs) are a family of hydrolytic enzymes consisting of three members, PON1, PON2, and PON3, located on human chromosome 7. Identifying the physiological substrates of these enzymes is necessary for the elucidation of their biological roles and to establish their applications in the biomedical field. PON substrates are classified as organophosphates, aryl esters, and lactones based on their structure. While the established native physiological activity of PONs is its lactonase activity, the enzymes’ exact physiological substrates continue to be elucidated. All three PONs have antioxidant potential and play an important anti-atherosclerotic role in several diseases including cardiovascular diseases. PON3 is the last member of the family to be discovered and is also the least studied of the three genes. Unlike the other isoforms that have been reviewed extensively, there is a paucity of knowledge regarding PON3. Thus, the current review focuses on PON3 and summarizes the PON substrates, specific activities, kinetic parameters, and their association with cardiovascular as well as other diseases such as HIV and cancer.

A Practically Unified Electrochemical Strategy for Ni-Catalyzed Decarboxylative Cross-Coupling of Aryl Trimethylammonium Salts.

By merging electrocatalysis and nickel catalysis, a unified strategy has been successfully applied to achieve the decarboxylative cross-coupling of four types of α-oxocarboxylic acids and their derivatives with aryl trimethylammonium salts under mild conditions. Our strategy provides a practical way for preparing aryl ketones, amides, esters, or aldehydes.

Direct Aerobic α-Hydroxylation of Arylacetates for the Synthesis of Mandelates.

Aerobic α-hydroxylation of α-methylene esters has proven challenging due to overoxidation and hydrolysis of the materials. In this article, KOtBu-promoted TBAB-catalyzed α-hydroxylation of α-methylene aryl esters using O2 as the oxygen source has been developed. Both low reaction temperature and catalyst TBAB are keys to success. This reaction provides an environmentally friendly and low-cost approach to mandelates, which are valuable building blocks and widely present in pharmaceuticals.

Chromium-Catalyzed Selective Cross-Electrophile Coupling between Unactivated C(aryl)–F and C(aryl)–O Bonds

Chemically inert C(aryl)–F bonds have rarely been used to couple with other unactivated bonds, and this remains a challenge because of the difficulty of the successive cleavage of two unactivated bonds by metal catalysis. We report here the chromium-catalyzed cleavage of chemically inert C(aryl)–F bonds for coupling with unactivated C(aryl)–O bonds, allowing cross-electrophile coupling between unreactive aryl fluorides and aryl esters to be achieved in high regio- and chemoselectivity. The reactive Cr, which was formed in situ by reducing CrCl2, enables cleavage of the o-C(aryl)–F bonds to afford monovalent and quartet cyclochromate; subsequent bipyridyl-enabled insertion into the ester C(aryl)–O bond followed by reductive elimination allowed the orthogonal coupling of these two different and unactivated bonds. Mechanistic studies indicate that the bipyridyl ligand greatly enhances the reactivity of Cr in the cleavage of C(aryl)–O bonds, and the second oxidative addition may occur sluggishly compared with the reductive elimination in the catalytic cycle.

Secondary metabolites of six Siberian and Crimean Armillaria species and their in vitro phytotoxicity to pine, larch and poplar

Basidiomycetes Armillaria infect deciduous, coniferous and fruit trees, causing enormous economic damage. The role of secondary metabolites (tricyclic sesquiterpene aryl esters - melleolides) in the life cycle and pathogenesis of Armillaria is under active investigation. To date, not all species of Armillaria have been tested for the biosynthesis of melleolides. We investigated the secondary metabolite profiles of six root-pathogenic species of the genus Armillaria (A. borealis Marxmüller & Korhonen, A. cepistipes Velenovský, A. gallica Marxm, A. mellea (Vahl) P. Kummer, A. sinapina Bérubé & Dessur, A. ostoyae (Romagn.) Herink) distributed in Siberia (South Krasnoyarsk Krai, Republic of Tyva, Republic of Khakassia, Taimyr Peninsula), Russian Far East (Sikhote-Alin) and Crimea (Krymsky National Park, Chatyr-Dag Mountain Lower Plateau). A total of 15 compounds were identified in the metabolome profile. Two compounds (melleolide D and melledonal C) are synthesized by all investigated strains irrespective of their geographic location and host plant. The maximum spectrum of melleolides (7-8 compounds) was found in isolates of A. borealis, A. gallica, A. sinapina, A. ostoyae. In submerged culture, the maximum accumulation of melleolides varied from 2 up to 239 mg l-1. A mixture of melleolide D and melledonal C (1:1) synthesized by the most productive strain A. mellea Cr2-17 was first found to have a phytotoxic action on the growth parameters of the callus culture Populus balsamifera and 10-day-old conifer seedlings. A 0.5% concentration of melleolides caused a credible decrease of P. balsamifera callus raw biomass; a decrease of the viability of Larix sibirica and, which is especially significant, Pinus sylvestris seedlings; inhibition of stem and root growth processes; dechromation of foliage; loss of turgor. The occurrence of a broad range of melleolides in the metabolome profile and two common compounds in all investigated strains, with a phytotoxic action at their sufficiently high concentration, enables considering the synthesis of melleolides by Armillaria fungi as one of the possible mechanisms of their pathogenicity efficiently realized in strains characterized by overproduction of melleolides under natural conditions.

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Diethylhexyl phthalate as a current problem of hygienic safety of packaging and packaged drinking water

Introduction. The chemical safety of packaged drinking water is influenced by many factors, including the quality of packaging materials. The chemical components included in the packaging can migrate into drinking water and have a negative impact on human health. The most common types of packaging for drinking water are polyethylene terephthalate (PET, PET) and polycarbonate (PC) bottles. In the production of polymers, to soften and increase the flexibility of the finished product, special substances are added to the material - plasticisers, including dialkyl or alkyl aryl esters of orthophthalic acid (phthalates), among which di (2-Ethylhexyl) phthalate (DEHP), which has toxic properties. The purpose of this study is to analyse various samples of plastic containers in contact with drinking water for the presence of DEHP in polymers and to study the emission of DEHP from polymer packaging into a model environment. Materials and methods. Research has been carried out on 11 samples of containers for drinking water of domestic production, of which nine samples were represented by PET bottles of various sizes and two samples of containers from PC with a volume of 19.0 litres. There was determined the content of DEHP in the container material and the level of migration of DEHP into the aqueous model environment. Sanitary and hygienic studies were carried out based on the Chemical Analytical Center “Arbitrage” of the DI. Mendeleev All-Russian Scientific Research Institute using gas chromatography with mass spectrometric detection (GC-MS). GSO 11366-2019 for the composition of a solution of orthophthalic acid esters in methanol was used as a standard sample for the calibration characteristics; a deuterated analogue of the analyte, DEHP-D4, was chosen as an internal standard. Results. In all studied samples of packaging materials, the residual content of DEHP was in the range of 1.7-4.2 mg/kg of polymer; the levels of DEHP migration into aquatic model media were determined at T = 20 °C and T = 40 °C in the range of (8.6-71.0) μg/dm3. Conclusion. One of the sources of contamination of packaged drinking water with DEHP is PET and PC containers. The results obtained indicate the need to include DEHP in the list of monitored sanitary and hygienic safety indicators in the technical regulations of the EAEU TR 044/2017 and TR CU 005/2011 and to consider the issue of restrictions on its use in the production of food packaging. Limitations of the study. As part of this work, samples of bottles from six domestic container manufacturers were analysed. To study the migration of the target component, a model medium was used - distilled water, which does not imitate the mineral composition of drinking water and has certain pH and electrical conductivity values. Studies of the level of DEHP migration were carried out at an ambient temperature of 20 °C and 40 °C and an exposure time of 30 days. The measurement range of DEHP in polymers and the model medium in this study was (0.1-5) µg/sample. The expanded uncertainty of the results of measurements of the DEHP content in the entire measurement range did not exceed 20%.

Competent synthesis of biaryl analogs via asymmetric Suzuki–Miyaura cross-coupling for the development of anti-inflammatory and analgesic agents

Based on the core structure of diflunisal drug, herein, we report a resembling series of biaryl analogs (3a–j) containing halogens, nitro, and methoxy substituents. They were designed and synthesized via a Suzuki–Miyaura cross-coupling reaction using Pd (OH)2 as a catalyst at a temperature of 65 °C with an intent to obtain improved and safer anti-inflammatory and analgesic agents. Suzuki–Miyaura transformation is the most significant among the cross-coupling reactions since its practical advantages include the commercially available low toxic reagents, mild reaction conditions, and functional group compatibility. On the other hand, a few conditions can be used to cross-couple aryl boronic acids or esters with aryl halides, especially 2-benzyl halides. Because of this, a novel Suzuki–Miyaura protocol is investigated that facilitates the selective conversion of halo aromatics, with an emphasis on the reaction to convert substituted bromobenzene to conjugated biphenyls. Finally, the obtained biaryl analogs (3a–j) were tested for in vitro and in vivo anti-inflammatory and analgesic applications. The results showed that compound 3b performed better than the standard drug with IC50 values comparable to that of the standard drug for COX-1 and COX-2 inhibition. Finally, molecular docking tests for the effective compound were carried out.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13738-021-02460-0.

Buchwald-Hartwig amination of aryl esters and chlorides catalyzed by the dianisole-decorated Pd-NHC complex.

A modular and generic method for the Buchwald-Hartwig amination reactions of relatively unreactive aryl esters as acyl electrophiles and aryl chlorides as aryl electrophiles has been developed, leading to the efficient synthesis of amides/amines under air conditions and with low catalyst loadings. The success of this catalytic protocol is mainly attributed to the modification of the Pd-IPr skeleton with sterically hindered and electron-donating anisole groups. This method also features good functional group tolerance and excellent chemoselectivities. In summary, the results presented herein suggest the possibility of developing a versatile and general protocol for diverse electrophiles to undergo the Buchwald-Hartwig amination reactions, avoiding too much consideration of the reaction conditions for the substrate-dependent C-N bond formations.

Preparation of magnetic silica supported Brønsted acidic ionic liquids for the depolymerization of lignin to aromatic monomers

A magnetic silica supported Brønsted acidic ionic liquid is employed in lignin depolymerization into aromatic monomers, such as aryl aldehyde, aryl ketone, aryl acid, and aryl ester.

Phytochemical screening by FTIR spectroscopic analysis of methanol leaf extract of herb Andrographis echioides

The plant Andrographis echioidesis play a vital role in curing various human diseases. According to traditional siddha medicinal system till date it is accountable as to cure 81 diseases. The cost of fresh leaves is Rs 1750/Kg in Medicinal live, a largest online medicinal supplier in India. This much of cost may be due to its demand in siddha medicine to prepare various medicine is so high. Even though, this much of demand is exists but no any scientific validation and documentation for this plant possessing phytocompounds to cure the disease. Hence the present study was aimed to evaluate the possible bioactive functional group present in the methanol leaf extract of Andrographis echioides. The major functional group present in this plant was determined by FTIR analysis showed the existence of functional groups such as alkanes, aromatic compound, conjugated alkene, cyclic alkene, nitro compound, aromatics, carboxylic acid, phenol, aromatics ester, alkyl aryl ether, vinyl ether, ester, tertiary alcohol, primary alcohol, alkyl halides, alkene and halo compounds.