Derivatives In Ionic Liquids Research Articles

Cholinesterase inhibitory activity and regioselective synthesis of spiropyrrolidinoindole integrated ferrocene hybrid heterocycles via multicomponent cycloaddition reaction

A novel spiroheterocyclic hybrid comprising several privileged structures comprising pyrrolidine, quinoxaline, indole and ferrocene moieties were synthesized in good yields in sustainable fashion using [Bmim]Br augmented four component cycloaddition process. A relatively less explored ylide prepared from quinoxalinone and L-tryptophan with diverse ferrocenyl derivatives in ionic liquids afforded spiropyrrolidinoindole tethered ferrocene hybrids. The reaction provides highly regioselective fashion thus created five new bonds and four adjoining stereocenter in single synthetic transformation, thus created with complete diastereomeric control. The cholinesterase inhibitory potency was performed for synthesized compounds against AChE/BChE enzymes. Among them, compound bearing with fluorine substituted heterocycles showed significant activity which is comparable activity with reference standard, galantamine.

Chemical accuracy prediction of molecular solvation and partition in ionic liquids with educated estimators

Ionic liquids (ILs) derivatives as novel green solvents are widely employed in laboratory and industrial applications. Many computational tools have been developed to compute various physiochemical properties of ILs species, e.g., mass density and viscosity. However, despite their central role as solvents, predictive tools for the solvation of external agents and the partition between water and ILs phases are rather limited. Common selections are atomistic simulations, especially the alchemical method. However, the relatively high computational costs could be harmful to large-scale applications. In this work, we develop a series of low-cost machine-learning estimators to exploit further the chemical-accuracy frontier. 1764 solvation and 1764 water-ILs transfer free energies involving 120 gaseous or drug-like solutes and many commonly applied ILs families are gathered from experimental references to form the dataset with a diverse coverage of chemical spaces. The best-performing tree-based method could predict simultaneously solvation and water-ILs biphasic partition thermodynamics with a state-of-the-art performance of ∼ 0.13 kcal/mol MAE, ∼0.25 kcal/mol RMSE, ∼0.98 Pearson r and ∼ 0.94 Kendall τ, beating transferable tools such as alchemical free energy calculations in a series of face-to-face comparisons.

Accurate modelling of pyrrolidinium ionic liquids with charge and vdW scaling

Molecular simulation as a complementing tool to experimental measurements has grown to be an instrument with predictive power for ionic liquids (ILs) derivatives. The combination of molecule-specific atomic charges generated with ab initio calculations and bonded and vdW parameters extracted from pre-fitted transferable force fields serves as the common practice in this field. Charge scaling is often applied to account for charge transfer and polarization effects and the scaling factor 0.8 has been concluded as a near-optimal solution in many scientific reports based on detailed analyses of various structural and thermodynamic observables. However, for ILs from the pyrrolidinium family investigated in the current work, we show that the charge scaling treatment cannot really minimize the experiment-simulation deviations to an acceptable level, which calls for further parameter adjustment. Following the modelling protocol summarized in our previous works, we tune the vdW radius of ILs-forming ions with a 298 K density scan and secure a parameter set that satisfactorily reproduces not only the room-temperature properties but also the mass densities in a large temperature range from 288 K to 348 K. The slopes of the vdW-scaling profiles are between −1.9 g/cm3 and −1.6 g/cm3, which are similar to quinuclidinium ILs investigated in our previous work. This phenomenon suggests the similarity of responding behaviors of the two ILs family during vdW scaling, and this range of response strengths could possibly be representative for ILs vdW scaling. Aside from bulk solvents, we further consider the interaction of ILs with a series of external organic agents. Following the previously accumulated experience, a slightly modified vdW scaling factor is picked as an option balancing different interactions within the heterogeneous solution. Nonequilibrium alchemical free energy calculations are conducted to compute solvation free energies in ILs and also the distribution (partition) behaviors of solutes between aqueous and ILs phases. The computed physiochemical properties involving pyrrolidinium ILs agree well with the experimental reference. Another feature of the selected pyrrolidinium ILs is the systematic variation of the length of the alkyl substituting chain, which enables a direct investigation of the chain-length dependence of the prediction accuracies for both bulk density and solvation/partition thermodynamics. Interestingly, with the chain-length variation, the error of bulk density exhibits a monotonic response, while a fluctuating (non-monotonic) behavior is observed for prediction errors of solvation and partition thermodynamics, which is related to the diverse features of solute-solvent interactions. Therefore, the observed behaviors of the properties of bulk solvents cannot be generalized to the solvation/partition behaviors of the same solvent, and accurate reproductions of bulk behaviors do not guarantee accurate calculations of solvation and partition thermodynamics.

Friedel-Crafts acylation of benzene derivatives in tunable aryl alkyl ionic liquids (TAAILs).

An iron(III) chloride hexahydrate-catalyzed Friedel-Crafts acylation of benzene derivatives in tunable aryl alkyl ionic liquids (TAAILs) has been developed. Through optimization of the metal salt, reaction conditions and ionic liquids, we were able to design a robust catalyst system that tolerates different electron-rich substrates under ambient atmosphere and allows for a multigram scale.

Molecular modelling of ionic liquids: Physical properties of species with extremely long aliphatic chains from a near-optimal regime

Basic issues of molecular modelling of ionic liquids with fixed-charge force fields are validated from extensive free energy calculations, component-specific force-field refitting, and box-size dependence of various properties in our previous works. It is found that the combination of scaled RESP charges and GAFF2 parameter set provides an accurate yet efficient option for atomistic simulations of ionic liquids derivatives. Based on hundreds of solvation and partition free energies accumulated for six typical room-temperature ionic solvents, the scaling parameter 0.8 is found to be a near-optimal solution universally applicable to most ionic liquids, due to its ability of simultaneously reproducing the experimental solvation, partition and bulk properties with small errors. In this work, we examine whether the previously obtained general guidelines on fixed-charge modelling of ionic liquids can be directly extended to unexplored species with structural features significantly different from the ions considered in our previous benchmark set. Specifically, the two ionic liquids under investigation involve a cation with extremely long aliphatic chains, which differs significantly from previous cations from the imidazolium family. The anions forming the two ionic liquids are also significantly different from those in our previous works. Numerical results of solvation thermodynamics of a spectrum of structurally diverse solutes in the two anhydrous ionic solvents, the water-ionic-liquids partition and the mass density using the recommended near-optimal fixed-charge modelling regime are in good agreement with experimental references, thus validating the applicability of the general guidelines proposed in our previous works.

Two-dimensional assessment of cobalt transport and separation through ionic polymer inclusion membrane: experimental optimization and artificial neural network modeling

In today's world, increasing technological demand and decreasing tenor of cobalt on the earth make the selective extraction and the recycling of cobalt processes indispensable. The study is to highlight both experimental optimization and artificial neural network (ANN) modeling of cobalt separation and transport performances through PVC-based ionic polymer inclusion membrane (IPIM) considering different molecular structure room temperature ionic liquids (RTILs) derivatives as an ion carrier. Some sophisticated investigations on PVC-based IPIMs have been done by changing membrane compositions. Also, the membranes were characterized in different aspects and techniques like SEM-EDX, AFM, contact angle measurement, etc. In optimum conditions, the initial mass transfer coefficient (Ji) of cobalt was found about 2,44x10−6 mols−1m−2 by the longest alkyl chain substituted ionic liquid (RTIL4) and also found that the selectivity of the process was found very well for cobalt in the presence of the other metal ions, especially toward nickel and cadmium. ANN modeling has been performed on the effective parameter analysis that was performed on the experimental results. As a result of ANN analysis, the most effective parameters were determined as RTIL type and operation time have higher modeling sensitivity. The promising results show experimentally optimized and ANN modeled process has a cost-effective, environmentally-friendly potential for cobalt separation and transport. Highlights Room temperature ionic liquids having different molecular structures in polymer inclusion membranes (PIMs) were effectively used for cobalt transport and separation. The process has considerable durability and reusability for long-term operations both cobalt separation and cobalt transport. A good coherence between experimental results and artificial neural networks (ANN) modeling was observed to create two-dimensional transport and separation effectiveness of cobalt. The best effective parameters on the cobalt transport and separation were found as RTIL type and operating time according to ANN modeling.

Electrochemical characterization and thermodynamic analysis of TEMPO derivatives in ionic liquids.

In this study we investigate the reversibility of the reduction process of three TEMPO derivatives - TEMPOL, 4-cyano-TEMPO, and 4-oxo-TEMPO. The [C2mim][BF4] and [C4mpyr][OTf] ionic liquids (ILs) were used to perform cyclic voltammetry (CV) to analyse the redox potentials of the TEMPO derivatives. The former was previously shown to quench the aminoxy anion of TEMPO through a proton transfer reaction with the cation, whereas the latter supported the irreversibility of the TEMPO reduction process. In CV results on TEMPO derivatives, it was shown that [C4mpyr][OTf] could allow for a high degree of reversibility in the reduction of 4-cyano-TEMPO and a moderate degree of reversibility in the reduction of TEMPOL. In comparison, reduction of 4-cyano-TEMPO was predominantly irreversible in [C2mim][BF4], whilst TEMPOL showed complete irreversibility. 4-Oxo-TEMPO did not show any notable reduction reversibility in either IL tested. Reduction potentials showed little variation between the derivatives and 0.2 V variation between the ILs, with the most negative reduction potential being observed at -1.43 V vs. Fc/Fc+ for TEMPOL in [C4mpyr][OTf]. To explain the varying degrees of reversibility of the reduction process, four types of side reactions involving proton transfer to the aminoxy anion were studied using highly correlated quantum chemical methods. Proton transfer from the IL cation was shown to have the ability to quench all three aminoxy anions depending on the IL used. On average, TEMPOL was shown to be the most susceptible to proton transfer from the IL cation, having an average Gibbs free energy (GFE) of 10.5 kJ mol-1 more negative than that of 4-cyano-TEMPO, which was shown to have the highest GFE of proton transfer. Side reactions between water and aminoxy anions were also seen to have the potential to contribute to degradation of the aminoxy anions tested, with 4-oxo-TEMPO being shown to be the most reactive to degradation with water with a GFE of -12.6 kJ mol-1. 4-Oxo-TEMPO was found to be highly susceptible to self-quenching by its aminoxy anion and radical form with highly negative proton transfer GFEs of -47.9 kJ mol-1 and -57.7 kJ mol-1, respectively. Overall, 4-cyano-TEMPO is recommended as being the most stable of the aminoxy anions tested with TEMPOL, thus providing a viable alternative to improve solubility should the IL be tuned to maximize its stability.

The one-pot synthesis of butyl-1H-indol-3-alkylcarboxylic acid derivatives in ionic liquid as potent dual-acting agent for management of BPH.

Based on the SAR of both α1-AR antagonists and 5α-reductase (5AR) inhibitors, the dual-acting agent 4-(1-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-1H-indol-3-yl)butanoic acid 4aaa was designed against BPH and synthesized by two steps of N-alkylation. One-pot protocol towards 4aaa was newly developed. With IL [C6min]Br as solvent, the yield of 4aaa was increased to 75.1% from 16.0% and the reaction time was shortened in 1.5h from 48h. 25 derivatives structurally based on arylpiperazine and indolyl butyric acid with alkyl linker were prepared. The protocol was futher extended to get another 14 derivatives wherein O-alkylation was involved, and applied to the synthesis of biologically efficient molecules DPQ and Aripiprazole. Expectedly, compound 4aaa exhibited dual inhibition of α1-AR and 5α-reductase, and exhibited no obvious cytotoxicity against human cells. The pharmacokinetic properties of 4aaa was also determined.

An efficient preparation and characterization of 1-(2-ethoxy-2-oxoethyl)imidazolium based ionic liquids derivatives as potential bioactive agents

A set of new 1-(2-ethoxy-2-oxoethyl)imidazolium-based ionic liquids (1–16) have been prepared via the alkylation reaction of ethyl 2-(1H-imidazol-1-yl)acetate with various type of substituted alkyl halides using a microwave irradiation reaction in yields above 90%. The chemical structures of the manufactured ILs (1–16) were analyzed by mass and NMR spectroscopy. The newly prepared ILs were examined for their in vitro anti-microbial activities towards different types of Gram (+) and Gram (−) bacteria, and also for their antifungal activities. The preliminary tests showed that most of the resultant ILs presented modest activities towards S. aureus and B. subtilis with IZ values ranging between 10 and 14 mm, while the E. coli activities was in the range of 16 and 20 mm. However, ILs (1–16) displayed poor activities against the C. albicans.

Thermodynamic Characteristics of Ionic Liquids Derived from Bromide Salts of 1,3-Dialkylbenzimidazole

The results of quantum-chemical calculations of the structure and energy of the hydrophobic ionic liquids derivatives of symmetric 1,3-dialkylbenzimidazole bromide salts using the hybrid functional B3LYP are reported. Natural bond orbital analysis has been used to evaluate the hydrogen bonds parameters. Heat capacity of the substances and their phase behavior were determined by DSC.

Ecofriendly microwave-assisted preparation, characterization and antitumor activity of some propylimidazolium-based Ionic liquids derivatives

ABSTRACT An ecofriendly and efficient preparation of a set of a new 1-propylimidazolium-based ionic liquids (1–20) has been manufactured by using both microwave irradiation and conventional procedure. Different spectral analysis (FT-IR, mass spectra, NMR and elemental analysis) were utilized to examine the structures of the newly prepared ILs. The in vitro antitumor activities of all ILs (1–20) were investigated, using viability assay, towards HEPG-2, MCF7 and CACO2 Cells. Among all tested ILs, the 3-(3-phenylpropyl)-1-propyl-1H-imidazol-3-ium tetrafluoroborate (13) showed better activity towards human hepatocellular carcinoma (HEPG-2) and colon carcinoma (CACO2), while the 3-(3-phenoxypropyl)-1-propyl-1H-imidazol-3-ium tetrafluoroborate (20) exhibited low IC50 values against human breast adenocarcinoma (MCF7) compared to the standard drug (5-fluorouracil (5-FU)). Generally, all ILs 1–20 derivatives showed moderate cytotoxic activity against all tested cell lines.

Solvation thermochemistry of aromatic hydrocarbons and their halogen derivatives in imidazolium-based ionic liquids

In this work solution enthalpies of aromatic compounds and their halogen derivatives in 1-butyl-3-methylimidazolium tetrafluoroborate [BMIM][BF4], 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide [BMIM][NTf2], 1-butyl-3-methylimidazolium trifluoromethanesulfonate [BMIM][TfO] were measured by solution calorimetry method. The solvation enthalpies of aromatic compounds and their halogen derivatives in ionic liquids were calculated. Based on experimentally measured solvation enthalpies and calculated non-specific solvation enthalpy the contribution of the solvophobic effect on the solvation enthalpy of dissolved molecules in ionic liquids was demonstrated to be negligible. The correlation between solvation enthalpies of the aromatic compounds and their halogen derivatives in ionic liquids and solute molecules polarizability parameter was found. Also, a comparison of relationships between solvation enthalpy and molar refractions in ionic liquids and molecular solvents was made.

Thermal properties of protic ionic liquids derivatives triethanolamine-based salts of mineral and organic acids

Phase behavior of twenty-one synthesized salts of triethanolammonium(tris (2-hydroethyl)ammonium) has been studied by the methods of differential scanning calorimetry (DSC) and thermogravimetric analysis (TG). It has been established that 18 of them are protic ionic liquids (PILs) with Tm 100 °C. The PILs have been divided into three groups according to their phase behavior in the DSC experiment. The phase behavior of each of the studied ionic liquids has been analyzed. Multiple regression has been obtained between the ionic liquids characteristics (such as melting, glass transition and decomposition temperatures) determined experimentally and the properties of the anions of the acids forming the PILs calculated by the quantum chemistry methods. It has been shown that there is a linear compensation effect between the changes in the entropy and enthalpy caused by triethanolammonium salts melting.

Emim][BF4]: An Efficient Green Protocol for the Synthesis of Bioactive 2‐(5‐(substituted)‐2,6‐dioxo‐1,2,5,6‐tetrahydropyrimidin‐4‐yl)‐2,3‐dihydrophthalazine‐1,4‐dione Derivatives

The present study is designed to synthesize the 2‐(5‐(substituted)‐2,6‐dioxo‐1,2,5,6‐tetrahydropyrimidin‐4‐yl)‐2,3‐dihydrophthalazine‐1,4‐diones and investigate their anticancer activity. This is the first example of the condensation reaction of a series of phthalhydrazide derivatives in ionic liquid. In this investigation, the titled compounds syntheses were carried out by simple and efficient three component coupling of phthalhydrazide, aldehydes, and barbituric acid in the presence of [Emim][BF4] ionic liquid. This methodology was provided and promotes the higher product yields in shorter reaction times and mild reaction conditions. The title compounds were tested for their anticancer activity. Some of them were shown the significant cytotoxic activity against the selected cancer cell lines.

Facile construction of novel fused chromeno[2,3-d]thiazolo[3,2-a]pyrimidine derivatives in biocompatible ionic liquid under solvent-free conditions_ESI

Facile construction of novel fused chromeno[2,3-<i>d</i>]thiazolo[3,2-<i>a</i>]pyrimidine derivatives in biocompatible ionic liquid under solvent-free conditions_ESI

Green Synthesis of 6‐Aryl‐5,6‐dihydrobenzo[4,5]imidazo[1,2‐c]quinazoline Derivatives in Ionic Liquid under Catalyst‐free Conditions

Using ionic liquids as green media, a series of 6‐arylbenzo[4,5]imidazo[1,2‐c]quinazoline derivatives is synthesized via a reaction of 2‐(1H‐benzo[d]imidazol‐2‐yl)aniline and benzaldehydes in the air. While the intermediate products of 6‐aryl‐5,6‐dihydrobenzo[4,5]imidazo[1,2‐c]quinazolines were obtained in high yields at the same conditions under nitrogen protection.

An efficient synthesis of quinazoline or pyrrolo[1,2-a]quinazolin-5(1H)-one derivatives in ionic liquids catalyzed by iodine

The iodine-catalyzed reaction of 2-amino-N′-arylbenzohydrazides and haloketones was carried out in ionic liquids and was found in good chemoselectivity. 5-Chloropentan-2-one selectively gave fused pyrrolo[1,2-a]quinazolin-5(1H)-one derivatives, and 6-chlorohexan-2-one only formed simple quinazolin-4(1H)-ones, while the second cyclization did not take place at all.

Solid Acid-Catalyzed Dehydration of Pinacol Derivatives in Ionic Liquid: Simple and Efficient Access to Branched 1,3-Dienes

The selective dehydration of pinacol derivatives to branched 1,3-dienes is extremely challenging because of the predominance of pinacol rearrangement. Herein, we successfully achieve this goal by employing a recyclable solid acid/ionic liquid catalyst system. The dehydration of alkyl- and cycloalkyl-derived diols in an Amberlyst-15/[Emim]Cl system afforded the corresponding 1,3-dienes in good yields, while a Nafion/[Emim]Cl system was demonstrated to be a better catalyst system for the dehydration of aryl-substituted substrates. Our protocol features straightforward and simple access to branched 1,3-dienes, high chemoselectivity, a recyclable catalyst system, a facile separation of dienes just by decantation, and a broad substrate scope.

Regioselective Synthesis of Spiro-2-aminopyrimidinone Derivatives in Ionic Liquid as Green Solvent

Regioselective Synthesis of Spiro-2-aminopyrimidinone Derivatives in Ionic Liquid as Green Solvent

One-Pot Four-Component Synthesis of 5,10-Diarylpyrido[4,3-b][1,6] Naphthyridine Derivatives in Ionic Liquids Catalyzed by TsOH

ABSTRACTA one-pot four-component reaction of aldehyde, aromatic amine, and two equivalents of piperidine-2,4-dione was treated in ionic liquids of [BMIm]Br catalyzed by TsOH (p-toluenesulfonic acid), and gave a series of 5,10-diarylpyrido[4,3-b][1,6]naphthyridine derivatives in good yields. This procedure has the advantages of mild reaction conditions, good yields, one-pot, and environmentally benign.