Hydrotropic Solution Research Articles

Ligand-free Pd catalyzed cross-coupling reactions in an aqueous hydrotropic medium

A simple, efficient and ligand-free protocol for the Suzuki–Miyaura reaction and base-free Heck–Matsuda reactions under mild reaction conditions has been developed over palladium supported on activated carbon (Pd/C) in an aqueous hydrotropic solution.

Mesoscale solubilization and critical phenomena in binary and quasi-binary solutions of hydrotropes

Hydrotropes are substances consisting of amphiphilic molecules that are too small to self-assemble in equilibrium structures in aqueous solutions, but can form dynamic molecular clusters H-bonded with water molecules. Some hydrotropes, such as low-molecular-weight alcohols and amines, can solubilize hydrophobic compounds in aqueous solutions at a mesoscopic scale (∼100nm) with formation of long-lived mesoscale droplets. In this work, we report on the studies of near-critical and phase behavior of binary (2,6-lutidine–H2O) and quasibinary (2,6-lutidine–H2O/D2O and tert-butanol/2-butanol–H2O) solutions in the presence of a solubilized hydrophobic impurity (cyclohexane). In additional to visual observation of fluid-phase equilibria, two experimental techniques were used: light scattering and small-angle neutron scattering. It was found that the increase of the tert-butanol/2-butanol ratio affects the liquid–liquid equilibria in the quasi-binary system at ambient pressure in the same way as the increase of pressure modifies the phase behavior of binary 2-butanol–H2O solutions. The correlation length of critical fluctuations near the liquid–liquid separation and the size of mesoscale droplets of solubilized cyclohexane were obtained by dynamic light scattering and by small-angle neutron scattering. It is shown that the effect of the presence of small amounts of cyclohexane on the near-critical phase behavior is twofold: (1) the transition temperature changes toward increasing the two-phase domain; (2) long-lived mesoscopic inhomogeneities emerge in the macroscopically homogeneous domain. These homogeneities remain unchanged upon approach to the critical point of macroscopic phase separation and do not alter the universal nature of criticality. However, a larger amount of cyclohexane generates additional liquid–liquid phase separation at lower temperatures.

Aqueous hydrotrope: an efficient and reusable medium for a green one-pot, diversity-oriented synthesis of quinazolinone derivatives.

A library of quinazolinones was prepared by the one-pot three-component reaction of isatoic anhydride, ammonium salts/amines, and various electrophiles using aqueous hydrotropic solution as an efficient, economical, reusable, and green medium giving good to excellent yields of products in very short time. The method offers a versatile way for the development of diversity-oriented synthesis of quinazolinones.

Exploring molecular insights into aggregation of hydrotrope sodium cumene sulfonate in aqueous solution: a molecular dynamics simulation study.

Hydrotropes are an important class of molecules that enhance the solubility of an otherwise insoluble or sparingly soluble solute in water. Besides this, hydrotropes are also known to self-assemble in aqueous solution and form aggregates. It is the hydrotrope aggregate that helps in solubilizing a solute molecule in water. In view of this, we try to understand the underlying mechanism of self-aggregation of hydrotrope sodium cumene sulfonate (SCS) in water. We have carried out classical molecular dynamics simulations of aqueous SCS solutions with a regime of concentrations. Moreover, to examine the effect of temperature change on SCS aggregation, if any, we consider four different temperatures ranging from 298 to 358 K. From the estimation of densities of different solutions we calculate apparent and partial molal volumes of the hydrotrope. The changes in these quantities increase sharply at a characteristic minimum hydrotrope concentration. The determination of molal expansibility at infinite dilution for different temperatures indicates the water structure breaking by SCS molecules, which is further confirmed by the calculations of water-water pair correlation functions. In comparison with typical surfactants in micelles, a slightly lower value of volumetric change upon aggregation per carbon atom suggests the formation of a more closely packed structure of hydrotrope aggregates. A close examination of different structural properties of hydrotrope solutions reveals that the hydrophobic interactions through their hydrophobic tails significantly contribute in hydrotrope aggregation,and the dehydration of hydrophobic tail at elevated temperatures is also visible. Remarkably, the aggregates have little or no impact on the average number of water-SCS hydrogen bonds.

Aza-Micheal Reaction in Glycerol as a Sustainable Hydrotropic Medium

The organic transformation carried out in suitable solvent as well as in presence of catalyst is more important due to its environmental impact. We try to optimize the organic transformation in aqueous hydrotropic solution because of it is a sustainable technique. Now days, the glycerine used as hydrotrope and it shows excellent hydrotropic properties. Glycerine has been show combine advantages of water like non-toxic, colourless, odourless liquid, large availability, renewability due to this important properties it recently proposed as a valuable green solvent.

THE APPLICATION OF HYDROTROPES AS MEDIUM IN THE EXTRACTION OF ANDROGRAPHOLIDE

Hydrotrope solutions provide safe and effective media for the microwave assisted extraction of andrographolide, the major bioactive chemical constituent of plant Andrographis paniculata. Microwave assisted extraction of androgpaholide was carried out by using hydrotropes, sodium benzoate and urea. The objective of this work were to determine the Minimum Hydrotrope Concentration (MHC) and to determine the effectiveness of each hydrotrope with respect to andrographolide at different system powers. The microwave assisted extractions of andrographolide were carried out at different concentration of hydrotropes (0.2-3M) and different system powers (39.9 and 119.7 Watt). Twenty grams of Andrographis paniculata dried powder were added to 200 ml of hydrotrope solutions and extracted in a microwave extractor for 15 minutes. The research result showed that the percentage of the microwave assisted extraction of andrographolide by using sodium benzoate and urea were up to 10.9% and 1.05% respectively. The Minimum Hydrotrope Concentration and the effectiveness of hydrotropes that was measured in term of Setschenow constant (K s ) were reported for two hydrotropes used in this study.

Statistically Comparable UV-spectrophotometric Method development for the Estimation of Probenecid in tablet Dosage Form with the Application of Hydrotropic Solubilization Phenomenon.

Statistically comparable method has been developed, validated, for estimating probenecid in tablet dosage form with the application of hydrotropic solubilization phenomenon. This research effort utilizes 2M sodium acetate as hydrotropic solubilizing agent which enhances the aqueous solubility of probenecid by 85 folds. The drug stability in hydrotropic solution was found to be more than 48hrs.The probenecid hydrotrope obeys the Beer’s – Lambert law at maximum wavelength of 244.5nm. The drug response was found to be linear in the range of 2 – 26 µg/ml with correlation coefficient of 0.9987.The non-interference of hydrotropic agent and additives in the course of probenecid estimation ensures the specificity of the proposed method.The mean recovery of 99.43% reflects its accuracy, obtained in good terms. The method precision results were found to be within limit expressed in %RSD (NMT 2%). The results of comparison of proposed method with standard method (IP 2010) were found to be in the similar range. The comparison provides evidence of proposed method to be simple, less time consuming, safe and eco-friendly. The validation (as per ICH 2005) of the proposed method accesses its use in the routinely quality control of probenecid in tablet dosage form.

Hydrotropy: monomer-micelle equilibrium and minimum hydrotrope concentration.

Drug molecules with low aqueous solubility can be solubilized by a class of cosolvents, known as hydrotropes. Their action has often been explained by an analogy with micelle formation, which exhibits critical micelle concentration (CMC). Indeed, hydrotropes also exhibit "minimum hydrotrope concentration" (MHC), a threshold concentration for solubilization. However, MHC is observed even for nonaggregating monomeric hydrotropes (such as urea); this raises questions over the validity of this analogy. Here we clarify the effect of micellization on hydrotropy, as well as the origin of MHC when micellization is not accompanied. On the basis of the rigorous Kirkwood-Buff (KB) theory of solutions, we show that (i) micellar hydrotropy is explained also from preferential drug-hydrotrope interaction; (ii) yet micelle formation reduces solubilization effeciency per hydrotrope molecule; (iii) MHC is caused by hydrotrope-hydrotrope self-association induced by the solute (drug) molecule; and (iv) MHC is prevented by hydrotrope self-aggregation in the bulk solution. We thus need a departure from the traditional view; the structure of hydrotrope-water mixture around the drug molecule, not the structure of the aqueous hydrotrope solutions in the bulk phase, is the true key toward understanding the origin of MHC.

Hydrotropic Extraction of Xanthones from Mangosteen Pericarp

A novel separation process for extraction of xanthones from mangosteen pericarp was investigated using aqueous hydrotrope solution. The hydrotropes sodium salicylate was used for the extraction. The effects of factors such as hydrotrope concentration, extraction temperature and solid loading were investigated by using Response Surface Methodology (RSM). The optimal conditions to obtain the highest yield of xanthones were 2M sodium salicylate, extraction temperature of 40°C and 3% solid loading. This hydrotropic extraction technique is simple and cost effective for the separation of bioactive compounds.Key words: Xanthones; Hydrotropes; Hydrotropic extraction

Behaviour of Pseudoisocyanine in Macromolecular and Hydrotropic Solutions

The photophysical behaviour of the dye pseudoisocyanine (PIC) was studied in macromolecular (sodium alginate) and hydrotropic (sodium toluenesulphonate and sodium styrenesulphonate) solutions. It was found that the placement of the dye in these media affected the spectroscopic properties and the lifetimes of its excited states. The effects are traced down to the interactions of the dye molecules with the macromolecules or their placement in the hydrotropic aggregates, inducing the formation of J-aggregates of the dye or constraining its internal movements reducing the rate of internal conversion. The lifetimes of the triplet state of the dye in alginate were of the order of 20-30 ns in freshly prepared solutions, whereas when leaving the solution to rest for some hours the decay became biexponential with the growing of a species with lifetime around 150 ns. The latter is assigned to dye molecules placed in the alginate network.

Microwave Assisted Attractive and Rapid Process for Synthesis of Octahydroquinazolinone in Aqueous Hydrotropic Solutions

We demonstrate here the synthesis of octahydroquinazolinone derivatives through one-pot, three-component condensation reactions of various aryl aldehydes, with a dimedone and urea in 50% aqueous hydrotropic solution (Sodium p-Toluene Sulfonate) under microwave irradiation. This method exhibits efficient and environmentally benign methodology with simple reaction workup for the rapid synthesis of library of octahydroquinazolinones. Moreover, the reaction medium can be easily separated from the product and subsequently reused many times. The present method is of great interest in the context of environmentally greener and safer processes.

Green hydrotropic extraction technology for delignification of sugarcane bagasse by using alkybenzene sulfonates as hydrotropes

A process for the delignification of sugarcane bagasse using aqueous hydrotropic solutions is investigated. The optimum conditions for the maximum delignification (85%) of bagssse comprise of temperature (388K), hydrotrope concentration (30% w/w), and bagasse loading (5wt%) in 240min. The delignification process was modeled as the extraction of lignin from the solid biomatrix to estimate its diffusivity at 3.43×10−13m2/s and activation energy 16.2kJ/mole. The isolated lignin is characterized in detail for surface functionality, nature and morphology (irregular shape, flaky/smooth surface, and amorphous nature), molecular weight (3791g/mole), phenolic compounds, and thermal stability (633K), by using, infrared spectrocopy (IR), scanning electron microscopy (SEM), X-ray diffraction (XRD), gel permeation chromatography (GPC), mass spectroscopy, UV spectroscopy, and differential scanning calorimetry analysis (DSC), respectively. The bagasse delignification using aqueous hydrotropic solutions has potential to overcome the problem of breaking of the cellulosic material in the conventional delignification processes.

ChemInform Abstract: Hydrotrope: Green and Rapid Approach for the Catalyst‐Free Synthesis of Pyrazole Derivatives.

An efficient synthesis of pyrazole derivatives by condensation of 1,3-diketone and hydrazines/hydrazides has been achieved in aqueous hydrotropic solution under catalyst-free conditions within a very short time. The present protocol is beneficial as it includes mild reaction conditions, shorter reaction times, use of universal solvent water, which avoids volatile organic solvents, high yields of products, and being environmentally friendly.

Phase behavior and mesoscale solubilization in aqueous solutions of hydrotropes

Hydrotropes are amphiphilic molecules that are too small to spontaneously form equilibrium structures in aqueous solutions, but form dynamic, non-covalent assemblies, referred to as clusters. In the presence of a hydrophobic compound, these clusters seem to get stabilized leading to the formation of long-lived, highly stable mesoscopic droplets, a phenomenon that we call “mesoscale solubilization”. In this work, we focus on the unusual mesoscopic properties of aqueous solutions of a nonionic hydrotrope, namely tertiary butyl alcohol (TBA), on addition of various hydrophobic compounds. Aqueous TBA solutions, in about 3–8mol% TBA concentration range and about 0–25°C temperature range, show the presence of short-ranged (∼0.5nm), short-lived (tens of picoseconds) molecular clusters which result in anomalies of the thermodynamic properties. These clusters are transient but do not relax by diffusion, thus distinctly different from conventional concentration fluctuations. In this concentration and temperature range, upon the addition of a third (more hydrophobic) component to TBA–water solutions, long-lived mesoscopic droplets of about 100nm size are observed. In this work, we clarify the ambiguity behind the definition of solubility and elucidate the phenomenon of mesoscale solubilization. A systematic study of the macroscopic and mesoscopic phase behavior of three ternary systems TBA–water-propylene oxide, TBA–water-isobutyl alcohol, and TBA–water-cyclohexane has been carried out. We differentiate between molecular solubility, mesoscale solubilization, and macroscopic phase separation. We have confirmed that practically stable aqueous colloids can be created from small molecules, without addition of surfactants or polymers. Such kind of novel materials may find applications in the design of various processes and products, ranging from pharmaceuticals to cosmetics and agrochemicals.

Novel UV spectrophotometer methods for quantitative estimation of metronidazole and furazolidone using mixed hydrotropy solubilization

Two simple, accurate, novel, safe and precise methods were developed for the simultaneous estimation of poorly water-soluble drugs Metronidazole (MTR) and Furazolidone (FZ) in a tablet dosage form using 2M sodium acetate and 8M urea solution (50:50%V/V) as a mixed hydrotropic solution. MTR and FZ show maximum absorbances at 319 and 364nm, respectively. Sodium acetate and urea solution did not show any absorbance above 240nm and thus no interference in the estimation of drugs was seen. MTR and FZ follow Beer’s law in the concentration range of 10–50μg/ml and 5–25μg/ml (r2=0.9992 and 0.9996). Method-A employs the simultaneous equation method using 319 and 364nm as two analytical wavelengths, method-B employs the absorption ratio method, which uses 339.2 and 364nm as two analytical wavelengths for estimation of MTR and FZ. The mean percent label claims of tablet dosage were found to be 98.715±1.012 and 98.74±0.912 in method A, 98.99±0.872 and 97.89±0.903 in method B for MTR and FZ, respectively. The developed methods were validated according to ICH guidelines and values of accuracy, precision and other statistical analysis were found to be in good accordance with the prescribed values therefore both methods can be used for routine monitoring of MTR and FZ in industry in the assay of bulk drug and tablets.

A Novel Approach using Hydrotropic Solubalization Technique for Quantitative Estimation of Entacapone in Bulk Drug and Dosage Form.

Analysis of drug utilized the organic solvent which are costlier, toxic and causing environment pollution. Hydrotropic solution may be a proper choice to preclude the use of organic solvents so that a simple, accurate, novel, safe and precise method has been developed for estimation of poorly water soluble drug Entacapone (Water Solubility-7.97e-(02) g/l). Solubility of entacapone is increased by using 8M Urea as hydrotropic agent. There was more than 67 fold solubility enhanced in hydrotropic solution as compare with distilled water. The entacapone (ENT) shows the maximum absorbance at 378 nm. At this wavelength hydrotropic agent and other tablet excipients do not shows any significant interference in the spectrophotometric assay. The developed method was found to be linear in the range of 4-20 μg/ml with correlation coefficient (r(2)) of 0.9998. The mean percent label claims of tablets of ENT in tablet dosage form estimated by the proposed method were found to be 99.17±0.63. The developed methods were validated according to ICH guidelines and values of accuracy, precision and other statistical analysis were found to be in good accordance with the prescribed values. As hydrotropic agent used in the proposed method so this method is Ecofriendly and it can be used in routine quantitative analysis of drug in bulk drug and dosage form in industries.

Hydrotrope: green and rapid approach for the catalyst-free synthesis of pyrazole derivatives

An efficient synthesis of pyrazole derivatives by condensation of 1,3-diketone and hydrazines/hydrazides has been achieved in aqueous hydrotropic solution under catalyst-free conditions within a very short time. The present protocol is beneficial as it includes mild reaction conditions, shorter reaction times, use of universal solvent water, which avoids volatile organic solvents, high yields of products, and being environmentally friendly.

Mesoscale inhomogeneities in aqueous solutions of small amphiphilic molecules

Small amphiphilic molecules, also known as hydrotropes, are too small to form micelles in aqueous solutions. However, aqueous solutions of nonionic hydrotropes show the presence of a dynamic, loose, non-covalent clustering in the water-rich region, This clustering can be viewed as "micelle-like structural fluctuations". Although these fluctuations are short ranged (approximately 1 nm) and short lived (10 ps-50 ps), they may lead to thermodynamic anomalies. In addition, many experiments on aqueous solutions of hydrotropes show the occasional presence of mesoscale (approximately 100 nm) inhomogeneities. We have combined results obtained from molecular dynamics simulations, small-angle neutron scattering, and dynamic light-scattering experiments carried out on tertiary butyl alcohol (hydrotrope)-water solutions and on tertiary butyl alcohol-water-cyclohexane (hydrophobe) solutions to elucidate the nature and structure of these inhomogeneities. We have shown that stable mesoscale inhomogeneities occur in aqueous solutions of nonionic hydrotropes only when the solution contains a third, more hydrophobic, component. Moreover, these inhomogeneities exist in ternary systems only in the concentration range where structural fluctuations and thermodynamic anomalies are observed in the binary water-hydrotrope solutions. Addition of a hydrophobe seems to stabilize the water-hydrotrope structural fluctuations, and leads to the formation of larger (mesoscopic) droplets. The structure of these mesoscopic droplets is such that they have a hydrophobe-rich core, surrounded by a hydrogen-bonded shell of water and hydrotrope molecules. These droplets can be extremely long-lived, being stable for over a year. We refer to the phenomenon of formation of mesoscopic droplets in aqueous solutions of nonionic hydrotropes containing hydrophobes, as mesoscale solubilization. This phenomenon may represent a ubiquitous feature of nonionic hydrotropes that exhibit clustering in water, and may have important practical applications in areas, such as drug delivery, where the replacement of traditional surfactants may be necessary.

Enhanced Solubility and Separation of m/p – Aminonitrobenze Using different Hydrotropic Solution

The aqueous solubilit ies of m/p - amino nitrobenzene in d ifferent concentrations (0-3.0 mo l/ L) of hydrotropes such as sodium benzoate, Sodiu m saccharin, dimethyl benzamide at different system temperatures (303K to 333K) were studied. The percentage extraction (%E) o f m- amino nitrobenzene fro m m/p - amino nitrobenzene mixture increases with an increase in hydrotrope concentration. A Minimu m Hydrotrope Concentration (MHC) in the aqueous phase was required to initiate the significance of the %E of m- amino nitrobenzene. Percentage extraction (%E) is the ratio of mo les of m - amino nitrobenzene extracted in presence and absence of a hydrotrope. The sensitivity and feasibility of the proposed process are examined by carrying out solubilization and equilibriu m precipitation experiments with the mixtu res of various compositions. The effectiveness of hydrotropes was measured in terms of Setschenow constant Ks and reported for all hydrotropes used in this study and determination of aggregation behavior of all hydrotropes were also studied. Cost effective and eco friendly techniques of removal of less soluble compoments.

Rheological characterization of mixtures of cetyl trimethylammonium bromide and sodium butyl benzene sulfonate in aqueous solutions

The rheological behavior of mixed aqueous solutions of cetyl trimethylammonium bromide (CTAB) and anionic hydrotropes, such as sodium salts of n-butyl benzene sulfonate (Na-NBBS), iso-butyl benzene sulfonate (Na-IBBS) and tert-butyl benzene sulfonate (Na-TBBS), has been studied over a range of the hydrotrope concentration at different temperatures. The zero shear viscosity measurements for the mixed systems show a bimodal curve with a first viscosity maximum at a Na-BBS/CTAB ratio of approximately 0.3 and other ones at about 2.5. The three isomers of butyl benzene sulfonate (BBS) differ in their effects on the viscosity of the solutions. The difference in the viscosities of the mixed CTAB–hydrotrope solutions is more prominent at higher values of Na-BBS/CTAB ratio. Since the viscosity depends on the microstructure generated by the CTAB-BBS mixtures in solutions, the size and shape of the mixed micelles varies with the structure of the butyl group. The linear NBBS induces higher changes even at lower concentrations. The CTAB-hydrotrope solutions in the region of the first viscosity maxima exhibit Maxwellian fluid behavior where the mixed system is highly viscoelastic and the micelles are entangled. In the region of second viscosity maxima, however, the mixed solutions are non-viscoelastic with much lower values of storage and loss modulii. The living polymer formation by linear growth of CTAB micelles, on addition of hydrotropes, to very large aggregation number is evidenced from intrinsic viscosity and rheological properties of solutions.