Nucleophilic Ring Opening Of Epoxides Research Articles

Rapidly Diverse Synthesis of N‐Aryl‐5‐Substituted‐2‐Oxazolidinones via Nucleophilic Epoxide Ring Opening and Intramolecular Acyl Substitution of Epoxy Carbamates

AbstractThe method for converting epoxy carbamates to oxazolidinones is outlined in this study. This innovative approach combines intermolecular nucleophilic epoxide ring opening with intramolecular acyl substitution in a single step, thereby facilitating rapid conversion. Significantly, this method effectively addresses challenges associated with the use of expensive reagents, harsh reaction conditions, and prolonged reaction times, presenting a more efficient alternative. Demonstrating favorable reactivity across a diverse range of aryl groups, as well as benzyl or tert‐butyl carbamates, the method consistently yields satisfactory results, with oxazolidinone formation ranging from 55 % to 99 % in over 24 examples. The synthesized oxazolidinones, including 5 v–5 x, hold substantial promise as intermediates for the synthesis of crucial synthetic molecules. Furthermore, the versatility of this method is underscored by its successful application in the formation of the 6‐membered ring 1,3‐oxazinan‐2‐one. These findings not only contribute to the advancement of synthetic methodologies but also pave the way for a streamlined synthesis of important pharmaceutical compounds.

A highly efficient and sustainable catalyst system for terminal epoxy-carboxylic acid ring opening reactions.

The nucleophilic ring opening of epoxides by carboxylic acids is an indispensable transformation for materials science and coating technologies. Due to this industrial significance, improvements in operational energy consumption and catalyst sustainability are highly desirable for this transformation. Herein, an efficient, environmentally benign and non-toxic halide free cooperative catalyst system based on an iron(iii) benzoate complex and guanidinium carbonate is reported. The novel catalyst system shows improved activity over onium halide catalysts under neat conditions and in several solvents, including anisole and nBuOAc. Detailed mechanistic studies using FeCl3/DMAP as a catalyst revealed the importance of a carboxylate bridged cationic trinuclear μ3-oxo iron cluster and guanidinium carbonate or DMAP as a carboxylate reservoir due to its superior activity.

Nucleophilic epoxide ring opening in the system "epichlorohydrin–carboxylic acids–tetrabutylammonium iodide–solvent (e=15.1–28.7)"

Nucleophilic epoxide ring opening in the system "epichlorohydrin–carboxylic acids–tetrabutylammonium iodide–solvent (e=15.1–28.7)"

Nucleophilic epoxide ring opening in the system "epichlorohydrin–carboxylic acids–tetrabutylammonium iodide–solvent (e=15.1–28.7)"

The mechanism of the oxirane ring opening by carboxylic acids with different volume of substituents in the system "epichlorohydrin(ЕCH)–RCOOH–tetrabutylammonium iodide–solvent (=15.1–28.7)" was studied in the excess of ECH at the temperatures of 40–800C by methods of chemical kinetics and correlation analysis. The effects of solvent polarity (ECH and its mixtures with THF and nitrobenzene), temperature, and spatial structure (topological steric effect index TSEI) of carboxylic acids on the proceeding of the reaction were investigated. The structure of the reaction products was determined by gas chromatography–mass and 1H NMR spectroscopy. It was found that the reaction accelerates with a decrease in the solvent polarity, an increase in temperature and steric effect in the structure of the reagent. It was shown that the tetraalkylammonium carboxylate (R'4N+–OOCR) which formed in situ causes the final product formation in the rate-determining step of the reaction mechanism.

PH-controlled regioselective nucleophilic ring-opening of epoxide: an improved process for the preparation of (R)-(-)- or (S)-(+)-3-hydroxytetrahydrofuran.

An environmentally benign, cost-effective and scalable process for the preparation of both the enantiomers of 3-hydroxytetrahydrofuran has been developed. pH-Controlled ring opening of enantiomerically pure epichlorohydrins with cyanohydrin is the key step of the process. The entire protocol does not require any column purification.

Highly Regioselective Ring-Opening of Epoxides: Synthesis and Biological Evaluation as Potent Antimicrobial Agents

In present work, a convenient method for the nucleophilic ring-opening of epoxides with secondary amine in presence of ethyl acetate as a polar aprotic solvent using catalytic amount of base is described. Present method is highly regioselective and furnishes the products in short time of period with excellent yield. The regioselectivity of this ring opening was confirmed using FT-IR, 1H NMR, 13C NMR, elemental analysis and mass spectral data. The antimicrobial screening of all these synthesized compounds was done against some bacterial and fungal strains in two polar solvents, DMSO and DMF using agar well diffusion method. These compounds showed good inhibition of bacterial strains and potent against fungal strains than standard drug.

Strategies for the Controlled Covalent Double Functionalization of Graphene Oxide.

Graphene oxide (GO) is a versatile platform with unique properties that have found broad applications in the biomedical field. Double functionalization is a key aspect in the design of multifunctional GO with combined imaging, targeting, and therapeutic properties. Compared to noncovalent functionalization, covalent strategies lead to GO conjugates with a higher stability in biological fluids. However, only a few double covalent functionalization approaches have been developed so far. The complexity of GO makes the derivatization of the oxygenated groups difficult to control. The combination of a nucleophilic epoxide ring opening with the derivatization of the hydroxyl groups through esterification or Williamson reaction was investigated. The conditions were selective and mild, thus preserving the structure of GO. Our strategy of double functionalization holds great potential for different applications in which the derivatization of GO with different molecules is needed, especially in the biomedical field.

Rongalite‐Promoted on Water Synthesis of Functionalised Tellurides and Ditellurides

AbstractThe on water reaction of sodium telluride with electrophiles has been explored. Na2Te, generated in situ through the rongalite (sodium hydroxymethanesulfinate)‐promoted reduction of elemental tellurium, reacts with a wide variety of electrophiles, including strained heterocycles, haloalkanes, Michael acceptors, and aryl diazonium salts, providing simple and rapid access to a broad range of novel functionalised symmetrical tellurides. The methodology well tolerated the presence of versatile functional groups such as alchohols, amines, esters, nitriles, and sulfones and allowed the incorporation of tellurium atoms into biologically relevant natural‐derived products. Furthermore, in the case of the nucleophilic ring opening of epoxides and aziridines, a judicious tuning of the reaction conditions enabled the synthesis of unreported β‐hydroxy‐ and β‐amino‐ditellurides, which were further employed as precursors of new functionalised unsymmetrical dialkyl tellurides. The thiol−peroxidase catalytic activity of hydroxy‐ditellurides has also been investigated in order to compare their antioxidant properties with those of homologous tellurides.magnified image

Synthesis and Characterization of γ-Fe2O3@HAp@β-CD Core-Shell Nanoparticles as a Novel Magnetic Nanoreactor and Its Application in the One-Pot Preparation of β-azido Alcohols, β-nitro Alcohols, and β-cyanohydrins

In this study, β-cyclodextrin(β-CD) supported, hydroxyapatite encapsulated γ-Fe2O3 (γ-Fe2O3@HAp@β-CD) was successfully prepared and evaluated as a solid-liquid phase transfer catalyst and also a molecular host system and nanoreactor for the nucleophilic ring-opening of epoxides in water for the preparation of β-azido alcohols, β-nitro alcohols, and β-cyanohydrins. The catalyst was characterized by FT-IR, XRD, TGA, and SEM. This procedure offers several advantages including excellent regioselectivity, high yields, short reaction times, recyclable catalyst, easy separation of the catalyst through external magnet, and easy work-up.

Facile Synthesis of Hydroxy-Substituted Thiacrown Ethers via Nucleophilic Ring Opening of Epoxides

The title thiacrown ethers were prepared in a one-step procedure to give a series of unique macrocycles possessing two unsubstituted hydroxy groups that can be easily functionalized. In addition, epoxides and macrocycles derived from Cookson’s birdcage diketone, were prepared. The nucleophilic ring opening of epoxides synthesis can be classified in the frame of click chemistry. Surprisingly, some of the prepared allyl substituted polyglycols as well as bis-epoxides, especially sulfur analogues, were prepared for the first time.

Studies towards the Total Synthesis of Cruentaren B

AbstractA highly stereoselective and an efficient approach for studies towards the synthesis of Cruentaren B has been described. The key steps involved in this synthesis are Prins cyclisation, nucleophilic epoxide ring opening, Alder‐Rickert reaction, SN2 displacement reaction and Lindlar's hydrogenation.

Nucleophilic ring-opening of epoxides: trends in β-substituted alcohols synthesis

The present review deals with the ring-opening of epoxides by various carbon, nitrogen, oxygen, halogen, and sulfur-containing nucleophiles, which most of the resulting products are versatile intermediates in the synthesis of various biologically active compounds. The regioselectivity and environmentally benign nature of procedures for the synthesis of similar products have been also discussed in detail.

Synthesis of Nucleosides through Direct Glycosylation of Nucleobases with 5-O-Monoprotected or 5-Modified Ribose: Improved Protocol, Scope, and Mechanism.

Simplifying access to synthetic nucleosides is of interest due to their widespread use as biochemical or anticancer and antiviral agents. Herein, a direct stereoselective method to access an expansive range of both natural and synthetic nucleosides up to a gram scale, through direct glycosylation of nucleobases with 5-O-tritylribose and other C5-modified ribose derivatives, is discussed in detail. The reaction proceeds through nucleophilic epoxide ring opening of an in situ formed 1,2-anhydrosugar (termed "anhydrose") under modified Mitsunobu reaction conditions. The scope of the reaction in the synthesis of diverse nucleosides and other 1-substituted riboside derivatives is described. In addition, a mechanistic insight into the formation of this key glycosyl donor intermediate is provided.

Mechanistic Studies of Cyclohexene Oxide/CO2 Copolymerization by a Chromium(III) Pyridylamine-Bis(Phenolate) Complex.

Chromium(III) chlorido amine-bis(phenolate) complexes paired with nucleophilic co-catalysts are a promising family of catalysts for the copolymerization of CO2 and epoxides to selectively produce polycarbonates with a very high degree of carbonate linkages. Single-component catalyst systems can be prepared, where the neutral nucleophile, 4-dimethylaminopyridine (DMAP), is coordinated to the metal site to provide a stable octahedral CrIII complex. These complexes possess the potential for both anionic (from the chlorido ligand) or neutral (DMAP) nucleophilic epoxide ring-opening during the proposed rate-determining initiation step. Concentration effect studies support a first-order dependence of the polymerization rate on the concentration of single-component catalyst. End-group analysis of polycarbonates by MALDI-TOF MS indicate the presence of predominantly DMAP-initiated chains as well as the occurrence of chain-transfer events resulting in ether linkages, likely from the presence of cyclohexene diol formed by the reaction of cyclohexene oxide and adventitious water.

An efficient method for regioselective ring opening of epoxides by amines under microwave irradiation using Bi(NO3)3·5H2O as a catalyst

Bi(NO3)3·5H2O a highly efficient environmentally benign catalyst, is used for the nucleophilic ring opening of epoxides with aromatic, aliphatic and heteroaromatic amines under solvent free microwave conditions to afford the corresponding β-amino alcohols in good to excellent yields with high regioselectivity.

A biomimetic diversity-oriented approach to the pseurotins

Pseurotins are a small family of secondary microbial metabolites isolated from the fermentation broth of Pseudeurotium ovalis. Pseurotin natural products possess a wide range of biological activities including inhibition of chitin synthase, inhibition of monoamine oxidase, antifungal, anti-angiogenic, and dopamine antagonistic activity. Structurally, the pseurotin family contains a highly substituted 1-oxa-7-azaspiro[4,4]non-2-ene-4,6-dione core (highlighted in red) that has been implicated in the biological activities of these natural products. Access to these natural products is limited due to poor fermentation yields or lengthy syntheses. To exploit therapeutic potential of the pseurotins, we are developing a biomimetic approach to the pseurotin core structure starting from readily available amino acids. The biomimetic approach consists of three main features: i) Condensation of a β-ketoester 4 and an amino acid 5 to form an epoxide 3; ii) α-Acylation to form a diketone 2; iii) Nucleophilic ring opening of epoxide to form the spiro-core 1.

Role of keto-enol tautomerization in a chiral phosphoric acid catalyzed asymmetric thiocarboxylysis of meso-epoxide: a DFT study.

The mechanism of a chiral phosphoric acid catalyzed thiocarboxylysis of meso-epoxide was investigated by density functional theory (DFT) calculations (M06-2X). The nucleophilic ring opening of epoxide by thiobenzoic acid was found to proceed via a concerted termolecular transition state with a simultaneous dual proton transfer to yield the β-hydroxy thioester product. Electrostatic interactions together with the steric environment inside the chiral catalyst play an important role in determining the enantioselectivity of the reaction.

Click functionalization of methacrylate-based hydrogels and their cellular response

Methacrylate-based hydrogels, such as homo- and copolymers of 2-hydroxyethyl methacrylate (HEMA), have demonstrated significant potential for use in biomedical applications. However, many of these hydrogels tend to resist cell attachment and growth at their surfaces, which can be detrimental for certain applications. In this article, glycidyl methacrylate (GMA) was copolymerized with HEMA to generate gels functionalized with epoxide groups. The epoxides were then functionalized by two sequential click reactions, namely, nucleophilic ring opening of epoxides with sodium azide and then coupling of small molecules and peptides via Huisgen's copper catalyzed 1,3-dipolar cycloaddition of azides with alkynes. Using this strategy it was possible to control the degree of functionalization by controlling the feed ratio of monomers during polymerization. In vitro cell culture of human retinal pigment epithelial cell line (ARPE-19) with the hydrogels showed improved cell adhesion, growth and proliferation for hydrogels that were functionalized with a peptide containing the RGD sequence. In addition, the cell attachment progressively decreased with increasing densities of the RGD containing peptide. In summary, a facile methodology has been presented that gives rise to hydrogels with controlled degrees of functionality, such that the cell response is directly related to the levels and nature of that functionality. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2014, 52, 1781–1789

Theoretical and Experimental Studies on the Regioselectivity of Epoxide Ring Opening by Nucleophiles in Nitromethane without any Catalyst: Nucleophilic-Chain Attack Mechanism

We describe here a mild and efficient method for the nucleophilic ring-opening of epoxides with amines, alcohols and water in the presence of nitromethane as a polar solvent without using any catalyst. The reactions are highly regioselective and afford the products in excellent yields within a short period of time at room temperature. The regioselectivity for this ring opening has been investigated using experimental and theoretical 1H and 13C NMR studies together with activation energy calculations at the B3LYP/6-311+G(2d,p) level of theory. The mechanism of nucleophilic attack has been investigated in terms of a direct attack or a methanol chain attack.

Regioselective synthesis of 2,3-dihydrobenzodioxepinones from epoxides and 2-bromophenols via palladium-catalyzed carbonylation

A highly regioselective cascade synthesis of 2,3-dihydrobenzodioxepinone from 2-bromophenols and epoxides has been developed. The reactions go through nucleophilic ring-opening of epoxides and subsequent palladium-catalyzed intramolecular alkoxylcarbonylation.