Solvent In Organic Synthesis Research Articles

One-pot Multicomponent Synthesis of Hydrazinyl Thiazoles Bearing an Isatin Moiety in Aqueous Medium

Abstract: Isatin-derivatives are an important class of nitrogen-containing heterocyclic compounds in organic synthesis. On the other hand, 1,3-thiazoles are 5-membered heterocyclic compounds containing nitrogen and sulphur atoms. Hydrazinyl thiazoles are often prepared through the classical condensation of aldehydes or ketones with thiosemicarbazide to yield thiosemicarbazones, which will then undergo heterocyclization with phenylacyl bromides to give the corresponding hydrazinyl thiazoles. Nowadays, multi-component reactions (MCRs) are considered the most powerful tool in organic synthesis. The use of water as a green solvent in organic synthesis is one of the goals of green chemistry. In this study, a series of new hydrazinyl thiazoles 3a-3u bearing an isatin moiety were synthesized in good yield via a one-pot three-component condensation reaction of isatins with thiosemicarbazide and phenyl acyl bromides in water under reflux condition. All the synthesized compounds were characterized by IR, 1D-NMR, 2D-NMR and LC/MS spectral data.

Discovery of Deep Eutectic Solvents in Organic Synthesis: An Insight into their Current Applications and Prospect

Discovery of Deep Eutectic Solvents in Organic Synthesis: An Insight into their Current Applications and Prospect

Recent Advances in Green Approaches for Synthesis of Oxindole Derivatives

Oxindole derivatives are nitrogen-containing, five-membered heterocyclic molecules found in both natural and synthetic substances with diverse biological functions. Owing to their pharmaceutical and therapeutic characteristics, oxindoles have received remarkable attention, and various oxindole-containing substances can be synthesized using many different approaches. With the discovery of the importance of oxindole derivatives in medicinal chemistry, mainly in drug synthesis, the demand for finding sustainable protocols has increased, as most classical methods have their limitations and flaws. Hence, it is crucial to establish efficient and sustainable techniques that are safe, cost-effective, have low energy consumption, and cause minimal environmental impact. Nowadays, the use of green solvents in organic synthesis has received much attention because they prevent the formation of waste, are environmentally friendly, and have easy work-up procedures. Green solvents such as water, deep eutectic solvents, ionic liquids, and polyethylene glycol can substitute hazardous solvents. Microwave irradiation, visible-light irradiation, electrochemical methods, and multi-component synthesis are all described under green approaches. Most of these approaches allow the reaction to proceed rapidly while releasing minimal waste into the environment. Recent discoveries in green chemistry applications can be considered a turning point in organic synthesis. This review focuses on promising green approaches, used for the synthesis of oxindole derivatives, carried out in recent years with typical examples in two sections: green solvents and green techniques.
 Keywords- Oxindole derivatives, Green solvents, Green techniques, Sustainable chemistry, Solvent-free.

Stability of Pd/C Catalysts in Solvents for Organic Synthesis

Stability of Pd/C Catalysts in Solvents for Organic Synthesis

Introducing Azomethine Imines to Chemical Biology: Bioorthogonal Reaction with Isonitriles.

Azomethine imines are valuable substrates for chemical synthesis in organic solvents that often require anhydrous conditions. Here, we introduce C,N-cyclic-N'-acyl azomethine imines (AMIs) to bioorthogonal reactions in an aqueous environment. These AMIs are stable under physiological conditions and react rapidly (k2 = 0.1-250 M-1 s-1, depending on pH) and chemoselectively with isonitriles in the presence of biological nucleophiles, including thiols. Live-cell imaging of cell-surface-bound isonitriles underlines the biocompatibility of the AMI-isonitrile ligation, and simultaneous one-pot triple-protein labeling demonstrates its orthogonality to commonly used bioorthogonal reactions, such as the SPAAC and iEDDA ligations.

The mechanism of methyl hydrazine degradation by supercritical water oxidation using ReaxFF simulation

Methyl hydrazine (MMH) is a key ingredient in rocket fuel as well as an important intermediate and solvent in organic synthesis. However, any remaining MMH in environment could be harmful to both people and the environment. In this work, we proposed a method for treating MMH pollution by supercritical water oxidation (SCWO) technology. Reactive molecular dynamics were used to reveal the microscopic mechanism of the oxidation decomposition of MMH. The results showed that the principle of SCWO is that the OH radicals are formed by the reaction between H2O and O2. It can effectively capture the H both in MMH and its decomposition fragments, thus speeding up the decomposition. At low temperature and low oxygen content, the initial decomposition of MMH has two main pathways: (1) CH3NHNH2 → CH3NH + NH2 (R1), and (2) CH3NHNH2 + OH → CH3NNH2 + H2O (R7). N2, CO2, and H2O are the final products. At high temperatures, the intermediate NH3 can be converted to N2. The activation energy of MMH decomposition with excess oxygen was also obtained by the Arrhenius equation as 29.3 kcal/mol.

Thermoreversible Cross-Linked Rubber Prepared via Melt Blending and Its Nanocomposites.

A covalent adaptable network based on the thermoreversible cross-linking of an ethylene–propylene rubber through Diels–Alder (DA) reaction was prepared for the first time through melt blending as an environmental-friendly alternative to traditional synthesis in organic solvents. Functionalization of the rubber with furan groups was performed in a melt blender and subsequently mixed with different amounts of bismaleimide in a microextruder. Cross-linking was confirmed by FT-IR spectroscopy and insolubility at room temperature, while its thermoreversible character was confirmed by a solubility test at 110 °C and by remolding via hot-pressing. Mechanical and thermomechanical properties of the obtained rubbers showed potential to compete with conventionally cross-linked elastomers, with stiffness in the range 1–1.7 MPa and strain at break in the range 200–500%, while allowing recycling via a simple melt processing step. Nanocomposites based on the thermoreversible rubber were prepared with reduced graphene oxide (rGO), showing significantly increasing stiffness up to ca. 8 MPa, ∼2-fold increased strength, and thermal conductivity up to ∼0.5 W/(m K). Results in this paper may open for industrially viable and sustainable applications of thermoreversible elastomers.

Understanding the promotional effects of trace doped Zn in Co/NC for efficient one-pot catalytic conversion of furfural to 2-methyl-tetrahydrofuran

2-methyl-tetrahydrofuran (2-MTHF) is a promising biofuel or fuel additive with excellent burning property, a versatile new-style solvent in organic synthesis, and an important medical intermediate. In this work, a one-pot selective conversion of furfural (FA) into 2-MTHF was carried out over Zn doped Co/NC catalysts. The Zn-Co/NC-1 catalyst with trace Zn dopant (0.38 wt%) exhibited the best performance (yield of 2-MTHF: 93.8%). According to the characterizations, it was found that the Zn not only incorporates into the carbon support but also partially dopes into Co nanoparticles. Subsequently, theoretical calculations demonstrated that the doping of Zn in carbon support can effectively enhance the electron transfer from the support to the metallic Co particle, leading to the electron-rich Co surface. The presence of Zn was found to promote the dissociation of hydrogen and to lower the diffusion barrier of hydrogen atom, in favor of the hydrogenation/hydrodeoxygenation processes. Furthermore, the Zn doped models exhibit much lower barrier in breaking C–OH bond of FOL, resulting in higher activity for hydrodeoxygenation of FOL. These theoretical results are consistent with the in situ FT-IR analysis of adsorption substrates and intermediates over Zn doped catalyst. This work reveals the mechanism of dopant Zn tailoring the electronic structure and catalytic performance of active sites, providing a deep insight into the design of economical and high-performance catalysts for hydrogenation/hydrodeoxygenation of biomass feedstocks.

“ON-WATER” RING OPENING REACTIONS: A REVIEW

The replacement of current organic chemical processes with more environmentally benign alternatives is an important goal from an ecological point of view. The study is aimed with the goal of promoting water as a solvent in organic synthesis. In recent years, extensive industrial and scholarly research has been promoted for the development of organic reactions in aqueous media. Using water as a solvent often promotes considerable rate enhancements and operational simplicity. Environmental benefits of using water are additionally highlighted in relation to the Twelve Principles of Green Chemistry.

Lemon Juice: A Versatile Biocatalyst and Green Solvent in Organic Transformations

AbstractGreen chemistry is the basis for fast‐growing, eco‐friendly, alternative sustainable technologies for the development of chemical products without the use or generation of hazardous catalysts. The role of naturally occurring fruit juice as a catalyst or solvent in organic synthesis has gained focused interest across the globe. Lemon juice‐mediated synthesis has been widely explored recently as a highly significant, selective solvent and biocatalyst in organic synthesis. This review presents recent developments on lemon‐juice mediated transformations and their application to synthesize molecules or building blocks of pharmaceutical interest. We believe this review article will be of interest to researchers both in academic and industrial settings focused on developing novel pharmacophores from a green chemistry principles perspective.

Cyrene: a bio-based novel and sustainable solvent for organic synthesis

This review highlights the use of Cyrene as an alternative green solvent in organic synthesis.

Dimethyl 2-(2,4-Diamino-3-cyano-5H-chromeno[2,3-b]pyridin-5-yl)malonate

Dimethyl sulfoxide (DMSO) is widely used as a solvent in organic synthesis and in pharmacology because of its low cost, stability, and non-toxicity. Multicomponent reactions are a powerful synthetic tool for the rapid and efficient construction of complicated molecular frameworks. In this communication, the multicomponent transformation of salicylaldehyde, malononitrile dimer, and dimethyl malonate in DMSO at room temperature was carefully investigated to give dimethyl 2-(2,4-diamino-3-cyano-5H-chromeno[2,3-b]pyridin-5-yl)malonate with good yield. The structure of the new compound was established by means of elemental analysis and mass, nuclear magnetic resonance, and infrared spectroscopy.

An insight of novel eutectic mixture between thiazolidine‐2,4‐dione and zinc chloride: Temperature‐dependent density functional theory approach

AbstractDeep eutectic solvents (DESs) are the mixture of a hydrogen bond donor (HBD) and a hydrogen bond acceptor (HBA) in a particular equivalent ratio. They gained popularity because of low melting point and green (non‐toxic) in nature. DESs showed promising ability as solvents and found to be better than traditional organic solvents and ionic liquids. They are being explored solvents in organic synthesis, substance dissolution, corrosion inhibition, biofuel generation, SO2/CO2 absorption, and extraction. In the present work, thioazolidine‐2,4‐dione (T) is taken as hydrogen bond donor, and zinc chloride (Z) is taken as hydrogen bond acceptor. Nine DESs are created using T and Z having different equivalent ratio. Further, they were studied using density functional theory (DFT) approach in gaseous state at different temperatures. T4Z1 found to most soluble in water as the dipole moment is maximum. Free energy of T1Z4 found to be least so may be most stable among all. Further, on changing the temperature from 298 to 323 K and then to 348 K, thermodynamic parameters are determined. Further, the change in free energy for the formation of the DESs are calculated in Hartree per particle as well in kcal/mol. At 298 K, the change in free energy for the formation of T2Z3 is minimum and indicates it feasibility or spontaneity at this temperature. But at temperature of 323 K, T1Z4 and T2Z3 are found to be same. Further, on increasing temperature to 348 K, the change in free energy for T1Z4 and T2Z3 is same and minimum. It means on changing the temperature, the spontaneity for the formation of DES changes. Based on the method of Jakob et al., it can be seen that the temperature changes with the change in composition, that is, the ratio of HBD and HBA. The composition of HBD and HBA is 1:2 and is called deep eutectic mixture as the melting temperature observed is least. There is not a complete agreement between the results obtained by DFT calculations and Jakob et al method.

Multicomponent Synthesis of 2-(2,4-Diamino-3-cyano-5H-chromeno[2,3-b]pyridin-5-yl)malonic Acids in DMSO.

Dimethyl sulfoxide is a widely used solvent in organic synthesis and in the pharmaceutical industry because of its low cost, stability, and low toxicity. Multicomponent reactions are an advanced approach that has become an efficient, economical, and eco-friendly substitute for the conventional sequential multi-step synthesis of various biologically active compounds. This approach was adopted for the synthesis of previously unknown 2-(2,4-diamino-3-cyano-5H-chromeno[2,3-b]pyridin-5-yl)malonic acids via transformation of salicylaldehydes, malononitrile dimer, and malonic acid. It was shown that the use of DMSO at room temperature makes it possible to synthesize previously unavailable compounds. The investigation of the reaction mechanism using 1H-NMR monitoring made it possible to confirm the proposed mechanism of the transformation. The structure of synthesized 5H-chromeno[2,3-b]pyridines was confirmed by 2D-NMR spectroscopy.

Trietyloamina. Metoda oznaczania w powietrzu na stanowiskach pracy z zastosowaniem chromatografii gazowej z detekcją płomieniowo-jonizacyjną

Triethylamine (TEA) is a tertiary aliphatic amine. At room temperature it is a colourless liquid with a strong ammonia odor. TEA is used as a substrat in production of quaternary ammonium compound, as a catalyst in polymerization process, as a solvent in organic synthesis and as an emulsifier in the production of dyes and pesticides. Occupational exposure to TEA can cause many adverse effects like skin, respiratory tract or eye irritation. TEA may cause also vision disorder like blurred vision or red-blue vision. The aim of this study was to develop and validate a method for determining TEA in workplace air. The developed method is based on the collection of TEA on sorbent tube filed with two sections of silica gel coated with hydrochloric acid. Silica gel is extracted with methanol:water mixture and resulted solution is analysed with capillary gas chromatography with flame-ionization detector. The study was performed using gas chromatograph equipped with DB-5ms column. The developed method is linear in the concentration range of 7.5–150 μg/ml, which is equivalent to the range of 0.03–6 mg/m3 for 100-L air sample. The analytical method described in this paper makes it possible to determine TEA in workplace air in the presence of other substances. The method is precise, accurate and it meets the criteria for procedures for determining chemical agents listed in Standard No. PN-EN 482. The developed method for determining TEA in workplace air has been recorded as an analytical procedure (see Appendix). This article discusses the problems of occupational safety and health, which are covered by health sciences and environmental engineering.

Microemulsion‐Based Gels for Lipase‐Catalyzed Ester Synthesis in Organic Solvents

AbstractMicroemulsions are clear, stable, isotropic mixtures of oil, water, and surfactant, frequently in combination with a cosurfactant. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drug delivery vehicles by incorporating a wide range of drug molecules. The purpose of this work is to solubilize in AOT [sodium bis(2‐ethylhexyl)sulphosuccinate] water‐in‐oil microemulsions at two different R‐values the Chromobacterium viscosum (CV) lipase and lipoprotein lipase ex Pseudomonas and to use them to catalyze the lactonization of 16‐hydroxyhexadecanoic acid at 40°C. CV lipase is also immobilized in gelatin‐containing microemulsion‐based gels (MBGs) with retention of catalytic activity. These lipase‐containing MBGs proved to be novel solid‐phase catalysts for use in apolar organic solvents. CV lipase‐containing MBGs are used to synthesize, on a preparative scale, a variety of different esters under mild conditions.

Reagent and Catalyst Capsules: A Chemical Delivery System for Reaction Screening and Parallel Synthesis.

Commercially available hydroxypropyl methylcellulose capsules are employed as a fast, safe, and user-friendly chemical delivery system containing all reagents (catalyst, ligand, and base) for three important transition-metal-catalyzed reactions: Buchwald-Hartwig, Suzuki-Miyaura, and metallophotoredox C-N cross-coupling reactions. This encapsulation methodology simplifies the screening of reaction conditions and the preparation of compound libraries using parallel synthesis in organic solvents or aqueous media. These reagents-containing HPMC capsules are easy to prepare, come in different sizes, and can be stored on the bench under noninert conditions.

Effect of starch microstructure on microwave-assisted esterification

Dry modification of starch, especially by microwave-assisted heating, has attracted increasing attention due to its various advantages, including energy saving, high conversion, rapidity, and avoidance of volatile organic solvents in organic synthesis. This work focuses on two fundamental issues: 1) effect of starch microstructure on dry modification; 2) effect of acid anhydride in solid and liquid states on the dry reaction, since their interfaces with solid starch are significantly different. Cornstarches with different amylose/amylopectin ratios were used to demonstrate the effect of starch microstructure, while two acid anhydrides, maleic (solid) and acetic (liquid) anhydrides, were used to study the reaction mechanisms. FTIR, SEM, XRD, and DSC were used to study the performance of modified starches and the mechanisms. It was found that the degree of substitution (DS) of starches modified by maleic anhydride generally increased with increasing amylose content since amylose contains more hydroxyl groups, resulting in higher sensitivity to microwaves. On the other hand, the DS of starches modified by acetic anhydride increased with increasing amylopectin content, since liquid acetic acid can diffuse into high-amylopectin starch granules. The higher amylopectin starches, waxy and maize, showed higher RC(%) and ∆H(%) than that of higher amylose starches G50 and G80.

Lemon juice mediated efficient and eco-friendly organic transformations

Lemon juice has been extensively explored recently as highly selective and efficient biocatalyst as well as green solvent in organic synthesis. Lemon juice holds considerable promise as cheap, easily available, biodegradable, nontoxic and easy-to-construct alternative to well-studied metal-based catalysts and also it is well consistent with green chemistry theme. The present digest paper primarily aims to illustrate the progress of lemon juice mediated organic transformations towards the synthesis of a wide variety of important organic compounds. The mechanistic aspects of the reactions have been highlighted as well.

Recent Advances of Sulfonylation Reactions in Water.

The sulfonyl groups are general structural moieties present in agrochemicals, pharmaceuticals, and natural products. Recently, many efforts have been focused on developing efficient procedures for preparation of organic sulfones. Water, a proton source, is considered one of the most ideal and promising solvents in organic synthesis for its easy availability, low cost, nontoxic and nonflammable characteristics. From the green and sustainable point of view, more and more reactions are designed proceeding in water. The review focuses on recent advances of sulfonylation reactions proceeding in water. Sulfonylation reactions using sodium sulfinates, sulfonyl hydrazides, sulfinic acids, and sulfonyl chlorides as sulfonating agents were introduced in detail. In this review, sulfonylation reactions proceeding in water developed in recent four yields were presented. Sulfonylation reactions using water as solvent have attracted more and more attention because water is one of the most ideal and promising solvents in organic synthesis for its facile availability, low cost, nontoxic and nonflammable properties. Numerous sulfonating agents such as sodium sulfinates, sulfonyl hydrazides, sulfinic acid, sulfonyl chlorides and disulfides are efficient for sulfonylation reactions which proceed in water.