Reactions In Organic Solvents Research Articles

An Overview of the Synthesis of Hexafluoroisopropanol and Its Key Intermediates

AbstractHexafluoroisopropanol (HFIP, 1,1,1,3,3,3-hexafluoro-2-propanol) is a fluorine-containing alcohol, which can be used in the preparation of fluorine-containing fine chemical, pharmaceutical, and pesticide ingredient. It is a widely used solvent in organic reactions that is miscible with water and many organic reagents. Hexafluoroacetone (HFA) is a key intermediate in the synthesis of HFIP. In this work, six methods for synthesizing HFA are discussed based on the different raw materials used. In addition, three methods of synthesizing HFIP, and the applications of HFIP are also reviewed.

Hansen solubility parameters sphere calculations and thermodynamic model fitting of two novel copper complexes supported by bis(imino)pyridine ligands

In this paper, two novel five-coordinated copper(II) metal complexes, [2,6-(ArN = CMe)2C5H3NCuCl2] (Ar = 2-EtC6H4, L1CuCl2; Ar = 4-EtC6H4, L2CuCl2), bearing bulky 2,6-bis[1-(2-ethylphenylimino)ethyl]pyridine ligands L1 (L1 = 2,6-(ArN = CMe)2C5H3N, Ar = 2-EtC6H4), 2,6-bis[1-(4-ethylphenylimino)ethyl]pyridine ligands L2 (L2 = 2,6-(ArN = CMe)2C5H3N, Ar = 4-EtC6H4) have been synthesized and characterized, and the thermodynamic properties of these complexes are reported in a variety of mono-solvents. The copper(II) metal complexes based on bis(imino)pyridine are widely used in catalysis, photoelectric material, biopharmaceuticals and other fields. In this paper, the solubility of L1 and L2 in four solvents, the solubility of L1CuCl2 in four solvents and the solubility of L2CuCl2 in five solvents were studied by static analysis. The solubility of these compounds was investigated in a certain temperature range to provide data to support the selection of optimal solvents for organic reactions, coating and crystallization separations. Hansen solubility parameters (HSPs) were used to explain the dissolution behavior of solutes and were found to be consistent with experimentally measured results. Moreover, the values of HSPs for L1CuCl2 and L2CuCl2 lacking Cu data were simulated by the Hansen Solubility Parameters in Practice (HSPiP) software, which allowed the prediction of solvents with good dissolution behavior. The values of total solubility parameter of Hildebrand (δ) for L1CuCl2 and L2CuCl2 are 24.5 and 23.0, respectively. Besides, solubility properties of L1CuCl2 and L2CuCl2 in two solvent mixtures at different percentages were predicted. In addition, seven thermodynamic models were used to correlate the solubility data. For L1 and L2, Polynomial models fit better with an average absolute relative deviation (ARD) less than 1 %; for L1CuCl2 and L2CuCl2, Polynomial model fits best (ARD < 1 %). In addition, the enthalpy–entropy compensation relationship in the dissolution process was analyzed by calculating the thermodynamic parameters of the substances, and the results showed that the dissolution process of L1 and L2 was an enthalpy-driven heat absorption process.

Conformational Landscape of the Hydrogen-Bonded 1-Phenyl-2,2,2-Trilfuoroethanol···1,4-Dioxane Complex: Dispersion Interactions and Conformational Conversion

A rotational spectrum of the hydrogen-bonded complex between 1-phenyl-2,2,2-trilfuoroethanol (PhTFE), a chiral fluoroalcohol, and 1,4-dioxane, a common solvent for organic reactions, was measured using a chirped pulse Fourier transform microwave spectrometer. Initial theoretical conformational searches were carried out using CREST, a recently developed conformational searching tool. Subsequent geometry optimization and harmonic frequency calculations at the B3LYP-D3(BJ)/def2-TZVP level of theory yielded nearly 30 binary conformers of which 13 are within an energy window of ∼5 kJ mol-1. Interestingly, while the O-H···O hydrogen bond dominates the attractive binary interactions, the complex conformational landscape is mainly controlled by subtle dispersion interactions between the phenyl and 1,4-dioxane rings. Two sets of rotational transitions were assigned in the experimental spectrum and attributed to the two most stable conformers of PhTFE···1,4-dioxane. The quantum theory of atoms in molecules (QTAIM), noncovalent interactions (NCI), and symmetry-adapted perturbation theory (SAPT) analyses were employed in order to appreciate how the phenyl ring and O-H functional groups influence the intermolecular interaction and conformational distribution of the binary complex. The main PhTFE conformation within the complex, identified experimentally, is different from that of the isolated PhTFE monomer reported previously.

In vitro cytotoxicity assessment of monocationic and dicationic pyridinium-based ionic liquids on HeLa, MCF-7, BGM and EA.hy926 cell lines

Dicationic ionic liquids (ILs) generally possess higher thermal and electrochemical stability than the analogous monocationic ILs, which makes them more suitable for high-temperature applications as solvents for organic reactions, lubricants or stationary phase in gas chromatography. However, knowledge on dicationic IL cytotoxicity is still scarce. Here we explore the cytotoxicity of twelve mono- and dicationic pyridinium-based ILs on HeLa, MCF-7, BGM and EA.hy926 cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell cycle arrest assays, apoptosis experiments and orange staining were carried out. The results showed that dicationic ILs are generally less cytotoxic than their monocationic counterparts. In monocationic ILs, cytotoxicity was stronger when they contain long alkyl chains, because of their higher lipophilicity. However, the full effect of the length of the linkage alkyl chain of dicationic ILs on cytotoxicity is not clear probably because the chain is “trapped” between both cationic moieties. IL cytotoxicity is highly dependent on the cell type, and HeLa cells exposed to [C12Pyr]Br die via apoptosis. The present study increases our knowledge of IL cytotoxicity on human and monkey cells and clarifies the cell death mechanism. The results suggest that dicationic ILs offer the potential to replace some monocationic ILs because of their lower cytotoxicity.

Theoretical study on ionic liquids based on DBUH+: Molecular engineering and hydrogen bond evaluation

AbstractThe new generation of the ionic liquids (ILs) based on 1,8‐diazobicylo [5,4,0] undec‐7‐ene (DBU) are applied as the solvent in organic reactions. In this work, by using a theoretical procedure, the most probable interactions between the ion pairs of DBUH+ based ILs, including 10 functionalized imidazole anions were investigated. For this purpose, the electrostatic potential surfaces were analyzed to detect the most probable interaction sites of DBUH+. On the basis of the obtained results, hydrogen bond formation between the anions and DBUH+ is influenced by the electronic effect of the substituted functional groups. This means that electron donating groups, such as phenyl has a stabilizing effect on the ion pairs, while electron‐withdrawing groups, such as nitro, induces a destabilizing effect. These behaviors are described based on the interaction energy values (ΔEint). To investigate the dispersion interaction effects in ILs formation, M06‐2X‐D3 functional was applied in energy analysis. The solvent reaction field was investigated by the polarizable continuum model in ethanol and chloroform as the solvent. The results showed that ethanol has a greater effect on the interaction energy of the ILs. Finally, to have a comprehensive understanding of the charge transfer effect on the stability of the studied ILs and to characterize the most probable interactions, natural bond orbital and quantum theory of atoms in molecules analyses were applied and the obtained results were analyzed.

Increased Production of Recombinant O-Phospho-L-Serine Sulfhydrylase from the Hyperthermophilic Archaeon Aeropyrum pernix K1 Using Escherichia coli

Background: O-phospho-L-serine sulfhydrylase from the hyperthermophilic archaeon Aeropyrum pernix K1 (ApOPSS) is thermostable and tolerant to organic solvents. It can produce nonnatural amino acids in addition to L-cysteine. Objective: We aimed to obtain higher amounts of ApOPSS compared to those reported with previous methods for the convenience of research and for industrial production of L-cysteine and non-natural amino acids. Method: We performed codon optimization of cysO that encodes ApOPSS, for optimal expression in Escherichia coli. We then examined combinations of conditions such as the host strain, plasmid, culture medium, and isopropyl β-D-1-thiogalactopyranoside (IPTG) concentration to improve ApOPSS yield. Results and Discussion: E. coli strain Rosetta (DE3) harboring the expression plasmid pQE-80L with the codon-optimized cysO was cultured in Terrific broth with 0.01 mM IPTG at 37°C for 48 h to yield a 10-times higher amount of purified ApOPSS (650 mg·L-1) compared to that obtained by the conventional method (64 mg·L-1). We found that the optimal culture conditions along with codon optimization were essential for the increased ApOPSS production. The expressed ApOPSS had a 6-histidine tag at the N-terminal, which did not affect its activity. This method may facilitate the industrial production of cysteine and non-natural amino acids using ApOPSS. Conclusion: We conclude that these results could be used in applied research on enzymatic production of L-cysteine in E. coli, large scale production of non-natural amino acids, an enzymatic reaction in organic solvent, and environmental remediation by sulfur removal.

(Invited) Polymer Electrolytes Based on Ionic Liquids for PEMFC and Lithium Batteries

Ionic liquids (IL) are considered as hi-tech new media with emerging applications as solvents for organic reactions or as electrolytes. The organization degree in these complex fluids is actually very challenging since it dictates microscopic as well as macroscopic properties. However in both electrochemical devises, i.e. the Proton Exchange Membrane Fuel Cells (PEMFC) and Lithium Polymer Batteries (LBP), polymer electrolytes with high conductivities and good mechanical properties are obtained by blending the IL with an appropriate polymer. We have shown recently that the membrane properties are guided by the IL structure, i.e. by its interactions with the host polymer1-5. We propose in this work a deep evaluation of the impact of IL structure on the membranes morphology and functional properties. The work is divided in two parts, discussing membranes for PEMFC and LPB. In the PEMFC, one class of ionic liquids with interesting properties, i.e. Protic Ionic Liquids (PIL), is extensively used. Our study is focused more specifically on a series of PIL obtained by reacting alkylamine with various acids6. In this work we show that well-chosen PIL incorporated in the membrane can act as smart nanoscopic probes able to reveal interesting information on the polymer organization. As example, the morphology of Nafion® membranes doped with PIL based on triethylammonium (TEA) and perfluorosulfonates with varying perfluoroalkyl chain length (C1, C4, C8) was investigated by small-angle neutron scattering (SANS). The membranes were carefully designed by solution casting method. The evolution of the SANS spectra of C1-TEA containing membranes is characteristic to the membranes swollen with polar species e.g. water as revealed by the shift of the ionomer peak toward small angles. In contrast, the introduction of C4-TEA and C8-TEA ionic liquids into Nafion® matrix, even in pretty large quantities, does not result in structural modifications at the nanoscale. Depending on the PIL structure and concentration, the resulting doped membranes exhibit very different functional properties (conductivity, water uptake, gas permeability coefficients, etc.). With respect with the safety, LPB solvent free polymer electrolyte films are very attractive in particular those made from poly(oxyethylene) (POE) host polymer. POE has outstanding ability to solvate lithium cation. It suffers however of various handicaps, namely (i) a high crystallinity that penalizes the electrolyte conductivity below the melting temperature (ii) a mechanical strength that vanishes following the polymer electrolyte melting and (iii) a stability in oxidation limited to roughly 3.9 V vs Li/Li+. In addition to the high performances such as the thermo mechanical, chemical, electrochemical properties, a special attention has to be paid to ion transport. The use of a battery based on solvent-free polymer electrolyte is partly conditioned by its melting temperature as the conductivity occurs mainly at the amorphous state. The architecture modification of POE is one of the routes to decrease the crystallinity but does not allow overcoming the bottleneck of a low cationic transference number, T+, in POE electrolytes. The use of IL such as tetraalkyl ammoniums is one of the routes to get sufficient conductivities at low temperatures but, once again, T+ remains low. Furthermore these ionic liquids, which benefit to the conductivity, do not participate in the electrode reactions. We have therefore directed our researches towards lithium-conducting ionic liquids. Hence, this work proposes to address these issues by designing new ionic liquid lithium salts containing the oxyethylene moiety (mPEG) and the perfluorosulfonate/ sulfonimide anion. Consequently, a large number of new ionic liquids were synthetized through original methods. The impact of (i) the number of oxyethylene units (ii) the different chemical structures and (iii) the anion on their intrinsic performances and those of the related polymer electrolytes was investigated. High cation transference numbers were obtained in host polymers based on linear POE or cross-linked POE, and its values increase with the lengthening of the mPEG. The adding of mPEG chain on the anion leads generally to greater conductivity of polymer electrolytes that increases with increasing mPEG lengths. 1)      R. Sood, C. Iojoiu, E. Espuche, et al. J. Memb.  Sci., 2015, 495, 445-456. 2)      R. Sood, C. Iojoiu, E. Espuche, et al. , J. Phys. Chem. 2014, 18  ( 26), 14157-14168. 3)      R. Sood, C. Iojoiu, E. Espuche, et al J. Phys. Chem. C, 2012, 116 ,  46,  24413-24423 4)      V. di Noto, E. Negro, JC. Iojoiu,  J. Am. Chem. Soc., 2010, 132, 2183-2193 5)      M. Martinez, C. Iojoiu, P. Judeinstein, et al., J. Power Sources, 2010, 195(18), 5829-5839 6)      P. Judeinstein, C. Iojoiu, J.-Y. Sanchez et al. J. Phys. Chem. B, 2008, 112, 12, 3680-3683.

Ferrocenyl Chalcones with 1- and 2-Naphthalenyl Group: Spectroscopic Characterizations and Electrochemical Properties

asshown in Scheme 1, and investigated their structural, elec-trochemical, and fluorescent properties. In this study, weprepared and characterized 1Naph-Fc (1Naph−C(O)CH=CH−Fc) and 2Naph-Fc (2Naph−C(O)CH=CH−Fc)(Scheme 2) and investigated their electrochemical and flu-orescent properties, compared to those of Fc-Naph (denotedfor both Fc-1Naph and Fc-2Naph) and the reactants. Two Naph-Fc (denoted for both 1Naph-Fc and 2Naph-Fc )compounds were prepared by the thermal reaction in organicsolvent and spectroscopically characterized. The UV-Visspectra of Naph-Fc compounds (Fig. 1) showed an absorptionband for the enone linkage at 319 nm ( e = 18.2×10

Sphalerite is a geochemical catalyst for carbon-hydrogen bond activation.

Reactions among minerals and organic compounds in hydrothermal systems are critical components of the Earth's deep carbon cycle, provide energy for the deep biosphere, and may have implications for the origins of life. However, there is limited information as to how specific minerals influence the reactivity of organic compounds. Here we demonstrate mineral catalysis of the most fundamental component of an organic reaction: the breaking and making of a covalent bond. In the absence of mineral, hydrothermal reaction of cis- and trans-1,2-dimethylcyclohexane is extremely slow and generates many products. In the presence of sphalerite (ZnS), however, the reaction rate increases dramatically and one major product is formed: the corresponding stereoisomer. Isotope studies show that the sphalerite acts as a highly specific heterogeneous catalyst for activation of a single carbon-hydrogen bond in the dimethylcyclohexanes.

ChemInform Abstract: Sodium Dodecylsulfate Induced Synthesis of Quinoxalines

Abstractvia reaction of o‐phenylenediamine with phenacyl bromides (17 examples)

ChemInform Abstract: Lactic Acid as an Invaluable Bio‐Based Solvent for Organic Reactions.

AbstractLactic acid is shown for the first time to be an effective promoting medium in a variety of multicomponent reactions mostly not requiring any catalyst.

Hmim][HSO4]: An Efficient and Reusable Catalyst for the Synthesis of Spiro[dibenzo[a,i]-xanthene-14,3'-indoline]-2',8,13-triones and Spironaphthopyran[2,3-d]pyrimidine-5,3'-indolines

These activities, combined with diverse chemicalbehavior make quinones attractive targets in organic syn-thesis.The removal of volatile organic solvents in organic reac-tions is the most important goal in green chemistry. One ofthe most efficient protocols to reach this aim is replacementof the volatile solvents with ionic liquids possessing lowvolatility, high thermal stability, non-flammability, recycl-ability and unique catalytic activity. During recent years,ionic liquids have attracted interest as environmentallybenign reagents due to their favorable properties and avariety of catalytic reactions have been successful usingionic liquids.

Influence of the hydrogen bonding on the basicity of selected macrocyclic amines

The optimized minimum‐energy geometries of different macrocyclic amines and their protonated structures were determined by using ab initio and density functional theory (DFT) calculations. All the gas phase optimizations and energy calculations were performed at the DFT/B3LYP/6‐311++G(d,p) level of theory. The HF/6‐31 + G(d,p) level was used for all single point calculations in the solution phase. Geometry optimizations indicate that the most stable structures are stabilized by intramolecular hydrogen bonds. The proton affinity (PA) of macrocyclic amines is controlled by the strength of intramolecular hydrogen bonds of macrocyclic amines. These hydrogen bonds strongly influence the basicity of heteroatoms in macrocycles. The highest PA value among the studied macrocyclic amines was found to be 264.9 kcal mol−1 for structure 7. This is comparable with PA of proton sponges such as 1,8‐bis(dimethylamino)naphthalene. The solution phase calculations were carried out in the dimethyl sulfoxide solution as a commonly used solvent in organic reactions. Natural bond orbital analysis was performed to calculate the charge transfers and the second‐order interaction energies (E(2)) between the donor and acceptor. Quantum theory of atoms in molecules (QTAIM) was also applied to determine the nature of hydrogen bonds. QTAIM studies showed that the intramolecular hydrogen bonds in these structures are electrostatic (closed‐shell) interactions as well as partially covalent and partially electrostatic in nature. Copyright © 2012 John Wiley &amp; Sons, Ltd.

Lactic acid as an invaluable bio-based solvent for organic reactions

Lactic acid was used, for the first time, as a bio-based green solvent to promote some organic reactions, such as three-component reactions of styrenes, formaldehyde and an active phenolic compound or N,N-dialkylacetoacetamides, three-component reactions of diethyl acetylenedicarboxylate, anilines and aromatic aldehydes, aniline-catalyzed condensations between salicylaldehydes and diethyl acetylenedicarboxylate, and the synthesis of substituted quinolines through Friedlander annulation between 2′-aminoacetophenone and 1,3-dicarbonyl compounds. In these reactions, lactic acid solvent exhibited many advantages including bio-based origin, superior synthetic efficiency, ease of isolating the product and good recyclability of the reaction medium. The concept of using lactic acid as a green solvent not only enriches the diversity and versatility of bio-based green solvents, but also offers us an effective means for designing environmentally benign synthetic systems.

Demonstration of a Runaway Exothermic Reaction: Diels–Alder Reaction of (2E,4E)-2,4-Hexadien-1-ol and Maleic Anhydride

In a demonstration that involves a solvent-free Diels–Alder reaction of (2E,4E)-2,4-hexadien-1-ol and maleic anhydride, one can use relatively small quantities of reactants to illustrate the process of scaling up a solvent-free reaction, including consideration of reactivity of the starting substances, scale of the reaction, and size and shape of the reaction vessel. Upon being mixed, the two solid compounds form a melt and react in the liquid phase to form a solid product. In a 50 mL beaker on a 5.00 mmol scale, the reaction was relatively uneventful. However, an increase to a 10.00 mmol scale in the same size beaker resulted in a vigorous exothermic reaction, which produced dark insoluble syrupy material. When water was added to the reaction mixture, the reaction was faster, with only a modest increase in the reaction temperature and 1,3,3a,4,5,7a-hexahydro-5-methyl-3-oxo-4-isobenzofurancarboxylic acid was obtained as a pure white solid. The demonstration may help students understand the role of solvents in organic reactions, why most reactions are carried out in solvents, as well as potential problems that may be encountered when developing solvent-free reactions.

Gluconic acid aqueous solution as a sustainable and recyclable promoting medium for organic reactions

For the first time, gluconic acid aqueous solution (GAAS), a biobased weakly acidic liquid, was used as an effective promoting medium for organic reactions, such as the Michael addition of indoles to α,β-unsaturated ketones, the electrophilic ring-opening reaction of 3,4-dihydropyran with indoles and Friedel–Crafts alkylation of electron-rich aromatics with benzyl alcohols. The concept of using GAAS as a solvent for organic reactions not only offers a sustainable candidate for progress in solvent innovation, but also opens up a new avenue for the utilization of this biobased polyhydroxylated acid. Among the features that render GAAS as a solvent so interesting is the ability to act as both the reaction medium and catalyst. Moreover, this methodology offers significant improvements with regard to the yield of products, simplicity in operation, cost efficiency and green aspects, in terms of avoiding toxic catalysts and minimizing the generation of waste.

A Green Multicomponent Reaction for the Organic Chemistry Laboratory. The Aqueous Passerini Reaction

Water is the ideal green solvent for organic reactions. However, most organic molecules are insoluble in it. Herein, we report a laboratory module that takes advantage of this property. The Passerini reaction, a three-component coupling involving an isocyanide, aldehyde, and carboxylic acid, typically requires ~ 24 h reaction times in organic solvents, but produces a quantitative conversion and yield in < 30 min when performed in water. This rate enhancement allows the Passerini reaction to be easily adapted for use in a second-year organic laboratory course. Additionally, the incorporation of this laboratory module facilitates discussions of both green chemistry and combinatorial chemistry in the curriculum.

Low Melting Sugar—Urea—Salt Mixtures as Solvents for Organic Reactions — Estimation of Polarity and Use in Catalysis.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Glycerol as a green solvent for high product yields and selectivities

Organic synthesis is usually performed in solution to dissolve both reactants and catalysts and to deliver heat. Here, we show that glycerol, which is a non-toxic, biodegradable, and recyclable liquid manufactured from renewable sources, has a high potential to serve as alternative green solvent for organic reactions. Several catalytic and non-catalytic reactions were successfully performed in glycerol. High products yields and selectivities were achieved. Besides solubility of the reactants and the catalysts and easy separation of the product, glycerol offers several other benefits such as catalyst recycling, microwave assisting reaction, and biphasic and emulsion modes.

Low melting sugar–urea–salt mixtures as solvents for organic reactions—estimation of polarity and use in catalysis

Mixtures of sugars, sugar alcohols or citric acid with urea and inorganic salts form stable melts if heated to 70 °C. The polarity of the melts was estimated using solvatochromic dyes and found to be in the range of DMF or water, depending on the sensitivity of the dye for hydrogen bonds. To explore the use of the melts as solvents in catalysis, Rh-catalyzed hydrogenations and Pd-catalyzed Suzuki reactions were performed. The hydrogenation of a double bond is sensitive to the composition of the melt, and no effect of the chiral melts on the stereochemical outcome of the reaction was observed. The Suzuki coupling proceeds rapidly, cleanly and quantitatively in all examined melts. The results recommend the non-toxic sugar–urea–salt melts as more sustainable reaction media for chemical transformations.