New fluorous/organic biphasic systems achieved by solvent tuning

Miscibility tests between 60 pairs of fluorous and organic solvents have been performed, and a number of biphasic systems based on hydrofluoroether solvents have been identified. Mutual solubilities of a series of fluorous and organic solvents have been measured to ascertain the compositions of the biphasic systems. A qualitative solvent tuning strategy based on solvent polarity and fluorophilicity/phobicity is introduced. Solvent tuning is then used to modulate the partition coefficients (P) of triarylphosphines with 0-3 fluorous tags. The results lay a foundation for future applications of these and related biphasic systems in catalysis and extraction.     

Oil-water partition coefficients from solvent activities

The activity coefficients of 1-octanol and 2-octanol in benzene at 20°C are reported here. These have been combined with literature data and used to estimate the 1-octanol-water partition coefficient for benzene. The value of 1200±100 on the mole-fraction scale agrees well with the literature value of about 1200.     

Determination of partition coefficients and residual solvent for polymer drying applications

Summary Gas-solid partition coefficients (K) for n-hexane in high density polyethylene (HDPE) have been measured at conditions applicable to large-scale drying utilizing a novel headspace method. The method features considerable versability and simplicity due to the control of experimental conditions designed to favor full extraction of the analyte into the headspace. By combining this full extraction technique with a traditional static headspace experimental scheme, a method which measuresK and residual concentration is achieved. The results show that partition coefficients differ significantly between HDPE in its virgin powder and pellet forms, as well as among various HDPE grades. The differences are shown to be attributable to differences in % crystallinity of the specific polymer. Data collected over a wide range of hexane concentrations reveals saturation levels (solubilities) which correspond to crossover from evaporative to diffusion-controlled drying.     

Prediction of partition and distribution coefficients in various solvent pairs with COSMO-RS

Performance of COSMO-RS method as a tool for partition and distribution modeling in 20 solvent pairs—composed of neutral or acidic aqueous solution and organic solvents of different polarity, ranging from alcohols to toluene and hexane—was evaluated. Experimental partition/distribution data of lignin-related and drug-like compounds (neutral, acidic, moderately basic) were used as reference. Several aspects of partition modeling were addressed: accounting for mutual saturation of aqueous and organic phases, variability of systematic prediction errors across solvent pairs, taking solute ionization into account. COSMO-RS was found to predict extraction outcome for both ligneous and drug-like compounds in various solvent pairs fairly well without any additional empirical input. The solvent-specific systematic errors were found to be moderate, despite being statistically significant, and related to the solvent hydrophobicity. Accounting for mutual solubilities of the two liquids was proven crucial in cases where water was considerably soluble in the organic solvent. The root mean square error of a priori logP prediction varied, depending mainly on the solvent pair, from 0.2 to 0.7, overall value being 0.6 log units. The accuracy was higher in case of hydrophilic than hydrophobic solvents. The logD predictions were less accurate, due to pK_a prediction being an additional source of error, and also because of the complexity of modeling the behaviour of ionic species in the two-phase system. A simple correction for partitioning of free ions was found to notably improve logD prediction accuracy in case of the most hydrophilic organic phase (butanol/water).     

Some observatons on the derivations of solvent polarity factors from gas-liquid partition coefficients

Summary The derivation by Snyder of polarity parameters from gas-liquid constants for 81 solvents has been re-examined. It is shown that the correction for the influence of the molecular size of the solvents and solutes by means of the Flory-Huggins entropy expression is more successful than the original correlation as carried out by Snyder. The correction for dispersive and/or entropic contributions to the free energy of transfer in the original treatment is found to be inadequate. However, the effect of various more refined treatments on the final polarity parameters P, x_e. x_d and x_n is probably small.     

Porous alumina-based fluorous liquid membranes: Dependence of transport on fluorous solvent

We report here the properties of supported fluorous liquid membranes based on porous alumina. The alumina is first rendered compatible with fluorous solvents by surface modification with an oligomeric perfluoropropylene oxide-based carboxylic acid, Krytox 157FSH. After modification, simply dipping the porous alumina membrane into a perfluorinated solvent results in a supported liquid membrane with high selectivity for fluorous compounds. Two homologous series of compounds differing in the number of -CF₂- groups were investigated, namely esters of cinnamyl alcohol and the analogous naphthyl derivative with 2H,2H,3H,3H-perfluoroalkanoic acids (HOOC-(CH₂)₂-(CF₂)_m−1CF₃, m = 2, 4, 6 and 8). Four perfluorinated membrane solvents (FC-77, PF-5080, FC-3283 and FC-43) were investigated. In FC-3283, the permeabilities, which are the products of a diffusion coefficient and a partition coefficient in the solution-diffusion model, of cinnamyl alcohol derivatives are 3.62 ± 0.36 times greater than those of the analogous naphthyl compounds for the solutes containing the same perfluorinated chain. Permeability, P, increases as the perfluorinated chain length increases in all of the perfluorinated solvents. Values of log(P) vs m are linear with a slope of 0.147 ± 0.002 but with different intercepts for the various solvents. Independent measurements of the partition coefficients of the solutes between the source/receiving phase solvent, ethanol, and the fluorous solvents reveal that the selectivity behavior is dominated by partitioning rather than diffusion. The free energy of transfer of a -CF₂- group (ethanol to perfluorinated solvents) is −1.1 kJ/mol. Despite the fact that the solvents are mixtures, not pure liquids, the partition coefficients are well correlated with values calculated based on group contributions with ‘mobile order and disorder’ theory. The diffusion coefficients of four solutes in four membrane solvents were also determined based on the solution-diffusion model. The Stoke-Einstein equation shows satisfactory estimation of experimental results.     

Selective solvent interactions in a fluorous reaction system

Mixtures of chloroform and perfluoro(methylcyclohexane) can be used as solvents for "fluorous" biphase reactions since they exist as two separate phases at low temperature but become a single phase at higher temperatures. Intermolecular nuclear Overhauser effects have been used to investigate the interactions of solvent components with the protons and fluorines of 3-heptafluorobutyrylcamphor in both phases of this biphasic system at 25 degrees C as well as the single phase at 54 degrees C. The results indicate that at 25 degrees C in the perfluorocarbon-rich phase, both solvent components interact with the solute selectively. There are no indications of unusual solute interactions of either solvent component in the chloroform-rich phase and only weak suggestions of selective interactions in the high-temperature phase. Various mechanisms for the enhancement of solute spin-solvent spin cross relaxation rates in the perfluoro(methylcyclohexane)-rich phase are considered. It is suggested that the solvation layer around the solute has a composition and possibly hydrodynamic properties different from those of the bulk solution in this phase. There are indications of appreciable regioselectivity of chloroform interactions with the hydrocarbon part of the solute in all phases.     

Determination of gas-liquid partition coefficients by gas chromatography

This review covers theoretical principles and experimental procedures for the determination of gas-liquid partition coefficients, KL, by gas chromatography. In order to precisely define the relationship between KL, retention time and experimental parameters, the retention theory, both for ideal and for imperfect gas phase, is expounded. The most important sources of systematic error, as peak asymmetry, mixed retention mechanisms, column hold-up time and stationary phase mass determination, are discussed. Although the review is focussed on packed columns, comparison to capillary columns is discussed in those aspects in which these last show advantages.     

New axially dissymmetric ligand recoverable with fluorous solvent

Axially dissymmetric ligands with perfluoroalkyl groups, (Ra)-2,2′-bis[(R)-1-hydroxy-1H-perfluorooctyl]biphenyl [(Ra)-(R)₂-1c] and its enantiomer, have been synthesized successfully by the coupling reaction of the corresponding aryl bromide using Ni(COD)₂. These ligands showed much higher asymmetric induction in the reaction of various aldehydes with diethylzinc than the trifluoromethyl (1a) or pentafluoroethyl (1b) analogues. Furthermore, 1c was recovered quantitatively by extraction with a fluorous solvent from the reaction mixture due to its high fluorine content. The recovered ligand 1c was pure enough to be reused without purification. The efficiency of 1c as the chiral ligand was not decreased at all even after seven times recycling.     

Determination of liquid-liquid partition coefficients by separation methods

By essence, all kinds of chromatographic methods use the partitioning of solutes between a stationary and a mobile phase to separate them. Not surprisingly, separation methods are useful to determine accurately the liquid-liquid distribution constants, commonly called partition coefficient. After briefly recalling the thermodynamics of the partitioning of solutes between two liquid phases, the review lists the different methods of measurement in which chromatography is involved. The shake-flask method is described. The ease of the HPLC method is pointed out with its drawback: the correlation is very sensitive to congeneric effect. Microemulsion electrokinetic capillary electrophoresis has become a fast and reliable method commonly used in industry. Counter-current chromatography (CCC) is a liquid chromatography method that uses a liquid stationary phase. Since the CCC solute retention volumes are only depending on their partition coefficients, it is the method of choice for partition coefficient determination with any liquid system. It is shown that Ko/w, the octanol-water partition coefficients, are obtained by CCC within the -1 < log Ko/w < 4 range, without any correlation or standardization using octanol as the stationary phase. Examples of applications of the knowledge of liquid-liquid partition coefficient in the vast world of solvent extraction and hydrophobicity estimation are presented.     

Calculation of single-ion partition coefficients

Single-ion partition coefficients have been calculated for NBu ₄ ⁺ and I⁻ in the system water—chloroform. The standard free energy of transfer of each ion was separated into an electrostatic and a neutral term. The electrostatic term was calculated with the aid of the Born equation. In the case of I⁻ the neutral term was calculated with the aid of the xenongas assumption, whereas in the case of NBu ₄ ⁺ the tetrabutylmethane assumption was used. The results of the calculation were compared with the experimentally found partition coefficient of the completely dissociated ion-pair NBu₄I.     

Perfluoroalkylated-pyridine catalyzed Aldol condensations of aldehydes and ketones in a fluorous biphasic system without fluorous solvent

Aldol condensation of different ketones with various aromatic aldehydes proceeds efficiently in the presence of catalytic amount of perfluoroalkylated-pyridine in a fluorous biphasic system without fluorous solvent, which has prompted various concerns involving cost, solvent leaching, and environmental persistence. The catalyst can be recovered by simple cooling and precipitation and used again.     

Recycling of fluorinated axially dissymmetric ligand with fluorous solvent

Axially dissymmetric ligand, (Ra)-2,2′-bis[(R)-1-hydroxy-1H-perfluorooctyl]-biphenyl (1), showing a high asymmetric induction, was found to be recovered quantitatively with a fluorous solvent from the reaction mixture owing to its high fluorine content. The recovered ligand 1 was pure enough to be reused without purification. The efficiency of 1 as the chiral ligand was not reduced at all even after seven times recycling.     

Unexpected fluorous solvent effect on oxidation of 1-thioglycosides

Oxidation of various 1-thioglycopyrano- and furanosides with H₂O₂/Ac₂O/SiO₂ was performed in CH₂Cl₂/aprotic perfluorinated solvent mixtures (100:0 to 1:19, v/v). Reactions appeared much faster at a solvent ratio of 1:1 without significant over-oxidation to sulfones and modification of diastereoselectivity. Nevertheless, the nature of both the glycosyl moiety and the protecting group influenced the (S_S):(R_S) product ratio.     

Estimation of partition coefficients by MEKC part 2: anthocyanins

The octanol-water partition coefficients of seven anthocyanins (in neutral form, pH = 7.0) were measured by means of MEKC. A new iterative method for the estimation of migration time of electroosmotic flow (EOF) and micelles in MEKC is presented. This calculation is based on Gauss-Newton linearization of the dependence between migration indices and migration times of a set of suitable standards and the application of an advanced statistical evaluation procedure. The values of partition coefficients obtained with the aid of an iterative process are compared with values obtained on use of EOF and micelle markers.     

CBS reductions with a fluorous prolinol immobilized in a hydrofluoroether solvent

A fluorous prolinol precatalyst bearing only 34 fluorine atoms has been immobilized in the hydrofluoroether solvent HFE-7500. The CBS reduction of acetophenone proceeded rapidly, in high yield and in high ee in the absence of any organic solvent. The organic product was stripped from the HFE-7500 phase with a polar solvent, and the HFE-7500 phase was reused "as is" with satisfactory results through eight runs. This process is an attractive prototype for the large-scale use, recovery, and reuse of fluorous organocatalysts.     

Fluorous distannoxane-catalyzed acetylation of alcohols in heterogeneous single fluorous solvent system

Acetylation of alcohols with an equivalent amount of acetic anhydride is feasible in the presence of fluorous distannoxane catalyst in heterogeneous single fluorous system. The fluorous layer containing catalyst can be recycled and reused at least 10 times.     

Determination of octanol/water partition coefficients by flow injection analysis

Determination of octanol/water partition coefficients by batch-extraction methods is currently the only acceptable procedure for application to structure/activity relationships. Work on the development of flow-injection systems to determine these partition coefficients is reported. It is shown that it is not necessary to know the concentration of the analytic in either phase; the partition coefficient should be equal to the differences in the octanol and water peak widths divided. by the system residence time. For a limited number of compounds, this is shown to be valid. Several systems were developed, including a flow-through dialyzer which was 5 times more efficient than the best commercial unit.     

Extraction of perfluorinated compounds from food matrices using fluorous solvent partitioning

Perfluorinated compounds (PFCs) such as perfluorooctane sulfonic acid (PFOS) have emerged as a new class of global environmental pollutant; they bioaccumulate and are persistent in the environment and in wildlife. Fluorine-fluorine interactions have been investigated as a means to isolate PFCs for mass spectrometric quantification. A novel sample extraction and cleanup procedure has been developed for fat-containing samples based on fluorous liquid-liquid extraction (F-LLE) in a triphasic solvent system consisting of hybrid:fluorous:organic solvent (trifluoroethanol:perfluorohexane/dichloromethane-saturated with water). This system partially separates fluorous from non-fluorous compounds, allowing removal of co-extractants, which had previously resulted in liquid chromatography mass spectrometry (LC-MS/MS) peak suppression preventing low-level detection of PFCs. The developed F-LLE was coupled with an existing extraction protocol allowing the limits of detection of PFCs to be lowered an order of magnitude for high fat samples. The developed workflow was used to show the absence of a range of eleven PFCs in nine UK and one Irish cheese samples. This representative application demonstrates a new application of fluorous-organic extraction in sample cleanup for measurement of fluorinated analytes in food, environment and broader analytical chemistry.