Cosolvent power

The cosolvency phenomenon was discovered in 1920 s experimentally for cellulose nitrate solution systems. Thereafter cosolvency has been observed for numerous polymer/mixed solvent systems. Polystyrene (PS) and polymethylmethacrylate (PMMA) are undoubtedly the most studied polymeric solutes in mixed solvents. Horta et al. have developed a theoretical expression to calculate a coefficient expressing quantitatively flie cosolvent power of a mixture (dTydx)o, where T,. is the critical temperature of the system and x is the mole fraction of hquid 2 in the solvent mixture, and subscript zero means x—>0. This derivative expresses the initial slope of the critical line as a function of solvent composition (Figure 5.4.1). Large negative values of (dT/dx) are the characteristic feature of the powerful cosolvent systems reported. The theoretical expression developed for (dT dx)o has been written in terms of the interaction parameters for the binary systems ... 

It was found that when the cosolvent power of the binary mixture increases, the complexing capacity decreases. These results were explained by taking into account the excess Gibbs free energy, G , and the order of the liquid. 

Addition of a cosolvent is an alternative mechanism to increase contaminant solubility in an aqueous solution. When a contaminant with low solubility enters an aqueous solution containing a cosolvent (e.g., acetone), the logarithm of its solubility is nearly a linear function of the mole fraction composition of the cosolvent (Hartley and Graham-Bryce 1980). The amount of contaminant that can dissolve in a mixture of two equal amounts of different solvents, within an aqueous phase, is much smaller than the amount that can dissolve solely by the more powerful solvent. In the case of a powerful organic solvent miscible with water, a more nearly linear slope for the log solubility versus solvent composition relationship is obtained if the composition is plotted as volume fraction rather than mole fraction. 

Trifluoromethyl hypofluorite is generally used at low temperatures with reactants dissolved in an inert solvent, but to increase the solubility of reactants a cosolvent (MeOH, acetone, THF) is often used however, it must be used with extra caution and appropriate safety precautions against explosions and fires, since trifluoromethyl hypofluorite is a powerful oxidizing agent. The toxicity of trifluoromethyl hypofluorite is expected to be high (as with fluorine). Fluori-nation reactions with trifluoromethyl hypofluorite have been discussed in the last twenty years in review papers6 11,65 and several monographs.12" 14... 

Sodium and lithium are the most common metals, and diethyl ether, tetrahydro-furan, and HMPA are often used as cosolvents to overcome solubility problems. The Benkeser method,37 204 employing lithium in low-molecular-weight amines (methylamine, ethylamine, ethylenediamine), is a more powerful reducing agent... 

Most researchers distil solvents for radical reactions in the same manner as they might for use with a reactive organometallic. This practice is recommended to ensure that solvents are sufficiently pure. That the solvents are simultaneously dried during purification is of little consequence. Water is a much poorer hydrogen atom donor than any common solvent (conversely, the hydroxyl radical is a powerful hydrogen atom abstractor). Thus, the presence of trace quantities of water will have no adverse effect on most radical reactions. As a corollary, water can be a useful solvent or cosolvent provided that the reagents or substrates are not susceptible to hydrolysis or protonolysis. 

The extensions of the Hildebrand and Hansen approaches are both empirical. Afterthe solubility behavior has been evaluated in a series of solvent systems, regression analysis can be used to estimate the empirical coefLcients, including th fferm of the extended Hansen approach, and then the solubility can be estimated in a solvent system which has not been included in the experimental portion of the study. The problem with acknowledging the predictive power of these equations is that the solubility in many solvents must be determined before being able to predict the solubility in the solvent of choice. It is probably easier to simply perform the solubility study in the solvent of choice and eliminate the prediction equation altogether. On the other hand, in a study of binary solvent systems consisting of water and a cosolvent appropriate to parenteral products, the solubility maximum in that series can be readily estimated by the mathematical expression Lnally achieved. 

Equation (3.46a) indicates that the solubility of the solute in a mixed solvent system increases as the volume fraction of the cosolvent increases. Figure 3.6 shows the solubilization of hydrocortisone butyrate in a water/propylene glycol system. From the plot of Equation (3.46a), In x2m vs. solubilizing power, o, of the cosolvent for the solute. The solubilizing power is related to the partition coefficient of the solute in a water/octanol system, Kwo, as follows ... 

The total solubility of weak acid in a water/cosolvent system [HA] ot can be determined by the solubility of the un-ionized species in water, the solubilizing powers, the hydrogen ion concentration, and the dissociation constant of the weak acid. Equation (3.49d) illustrates that the total solubility of the weak acid will increase exponentially with respect to the volume fraction of the cosolvent. Even though the solubilizing power of the cosolvent for the un-ionized species is usually larger than that of the ionized species, the solubilization of the ionized species is very important in determining the total solubility when pH - pKa > oIIA - oa. ... 

This was not the case when alkynes were employed for 5-exo-dig cyclizations, nor when the radical ring closure required an energetically less favorable P-oriented anomeric radical. Low yields of the C-glycosides were characteristic for both instances as depicted in Figure 7. Whereas the cyclization rates could not readily be modified, it seemed more appropriate to diminish the rate of the competitive second electron transfer step by modifying the reducing power of Smij through the omission of the cosolvent, HMPA. Of course, this could... 

---