A Solvent Selection

Apparatus Test tubes (10-mm x 75-mm), hot-water (80-100 °C) or steam bath. 

Protocol For known compounds, place about 20 mg (a microspatula-tip full) of the finely crushed solid in a test tube and add about 0.5 mL of water using a calibrated Pasteur pipet. Stir the mixture with a glass rod or microspatula to determine whether the solid is soluble in water at room temperature. If the solid is not completely soluble at room temperature, warm the test tube in the hot-water or steam bath, and stir or swirl its contents to determine whether the solid is soluble in hot water. 

If any of your solutes is soluble in the hot solvent but only slightly soluble or insoluble at room temperature, allow the hot solution to cool slowly to room temperature and compare the quantity, size, color, and form of the resulting crystals with the original solid material. 

Repeat the solubility test for the solutes using 95% ethanol and then petroleum ether (bp 60-80 °C. 760 torr). After completing these additional tests, record which of the three solvents you consider best suited for recrystallization of each of the solutes. 

Compounds 1-4 contain a variety of functional groups that impart differing solubility properties to the molecules and are possible substrates on which to practice the technique of determining solubilities. Other known compounds may be assigned by your instructor. 

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Before the coupling reaction, the self-assembly of PI-Z>-PS-Z>-PI triblock copolymer chains in w-hcxane was investigated by LLS. Figure 7 shows typical hydrodynamic radius distributions (/(Rh)) of individual PI-Z>-PS-Z>-PI triblock chains in THF, a good solvent for both the PI and PS blocks, and the core-shell micelles formed via the self-assembly of the triblock copolymer chains in -hexane, a solvent selectively good for the PI block. The shifting of the peak from... 

This scheme of frequency tripling was successfully tested with fuchsin in hexafluorisopropanol (a solvent selected for its low index of refraction and relatively flat dispersion curve) to frequency-triple the output of a neodymium laser 67,68) With an input power of 10 MW/cm2 a third-harmonic output of 0.2 mW/cm2 was measured. This low value was mainly due to the relatively high absorption of fuchsin at 355 nm. An improvement of the efficiency by a factor of 80 was found with hexamethylindocarbocyanine iodide in hexafluorisopropanol because of the much lower absorption of this dye at 355 nm. Since the absorption minimum of this dye is at 383 nm, one could expect an additional efficiency increase by a factor of 70 for a fundamental laser wavelength of 1.15 / 69>. Other cyanine dyes have been used for frequency tripling a fundamental wavelength of 1.89 /mi 70>. 

ACS GCl Pharmaceutical Roundtable (2008) Collaboration to deliver a solvent selection guide for the pharmaceutical industry. Presentation at the AIChE Annual Conference, http //aiche. confex. com/aiche/2008/techprogram/ P125149. HTM (last accessed 22 October 2008). 

Tabic 3.5 Predictions of Zhulina and Birshtein (1985) for micellar characteristics in an AB diblock in a solvent selective for the A block"... 

Thus, copolymers of the same composition can have qualitatively different sequence distributions depending on the solvent in which the chemical transformation is performed. In a solvent selectively poor for modifying agent, hydrophobically-modified copolymers were found to have the sequence distribution with LRCs, whereas in a nonselective (good) solvent, the reaction always leads to the formation of random (Bernoullian) copolymers [52]. In the former case, the chemical microstructure cannot be described by any Markov process, contrary to the majority of conventional synthetic copolymers [ 10]. 

RO occurs when a solution is pressurized against a solvent-selective membrane, and the applied pressure exceeds the osmotic pressure difference across the membrane. Water is the solvent in most existing reverse osmosis applications the solutes may be salts or organic compounds. 

The first self-assembling block copolymers were PS-fe-PMPS- -PS synthesised by Matyjaszewski and Moller. They observed micellar aggregates by ATM after casting dilute dioxane solutions (a solvent selective for the PS block) of the copolymer. The observed micelles were taken to have internal PMPS cores and were measured at 25-30nm in diameter [73], The hrst self-assembling amphiphilic polysilane block copolymers to be investigated was the PMPS-PEO multi-block copolymer with normal distribution PMPS blocks and uniform low polydispersity PEO blocks. After dialysis aqueous dispersions of this copolymer formed micellar as well as vesicular structures [78, 79] as shown in Eig. 19. 

We next carried out selective esterification of two substrates in this reaction system. When a 1 1 mixture of lauric acid and acetic acid was esterified with dodecanol in the presence of DBSA under neat conditions at 40°C for 48 h, the laurate ester and the acetate ester were obtained in 63% and 35% yields, respectively (Table 13.7, entry 1). On the other hand, when the same reaction was conducted in water, the laurate ester was predominantly obtained in 81% yield, and the yield of the acetate was only 4% (entry 2). Similar selective esterification of lauric acid over acetic acid was also observed in the reaction of another alcohol (entry 4), Furthermore, even cyclohex-anecarboxylic acid, which is an a-disubstituted acid, was preferentially esterified in the presence of acetic acid (entries 5 and 6). These selectivities are attributed to the hydrophobic nature of lauric acid and cyclohexanecarboxylic acid as well as to the high hydrophilicity of acetic acid. These unique selectivities became possible by using water as a solvent. Selective esterification based on the difference in hydrophobicity was also attained in the reaction of two alcohols, one of which is hydrophobic and the other water-soluble. 

Pfizer have developed a solvent selection tool, which has been used to educate researchers about solvent replacement and has resulted in reduced amounts of chlorinated and ethereal solvents being used in their research labs. A reduced availability of less desirable solvents also encouraged the uptake of alternatives. For example, hexane was replaced by heptane in stockrooms. The chart shown in Figure 1.5 could be applied to other industries and is easily used in academic research labs. It has been modified to take into account the findings of Fischer and co-workers, and as a result acetonitrile and THF have been transferred from usable to undesirable based on their performance in LCA. 

If you are not sure of the identity of the compound you have prepared or if it is a new compound, you must carry out a solvent selection to find out which solvent is the most appropriate (p. 93). 

Box 13.1 How to carry out a solvent selection for recrystallization of an unknown compound... 

In general, a solvent selected for the titration of a weak acid should itself be a much weaker acid (or neutral) and usually should be basic enough compared with water as solvent to increase the extent of dissociation. Comparably, for a weak base the solvent should be a much weaker base and acidic enough to increase the extent of dissociation. For the possible differentiation of acids that are all strong in water, the choice of a solvent less basic than water is appropriate. The solvent should also dissolve the sample, and the reaction products should be either soluble or rapidly form... 

If these parameters are used for the construction of a diagram as shown in Figure 5.1, a solvent selectivity triangle is obtained which clearly shows the differences between the individual solvents with regard to their dipolar (re ), acidic (a) and basic (/3) properties.2 The largest differences in the elution pattern can be expected if solvents are chosen which are as far apart from each other as possible. Because mixtures of two solvents, A and B, are used in most cases, only such solvents can be chosen which are miscible with each other. The usual A solvent in normal-phase separations is hexane, in reversed-phase separations it is water. Therefore the possible B solvents are limited in number. With regard to selectivity, it makes no real sense to try a normal-phase separation with diethyl ether as well as with tert, butyl methyl ether because all aliphatic ethers are located at the same spot in the selectivity triangle. Likewise it is not necessary to try several aliphatic alcohols for reversed-phase separations. 

Perhaps 90% of all rHPLC separations use a Cig stationary phase. In SFC, there is a much wider choice. The vast majority of SFC separations have been performed on totally porous silica, usually with a bonded organic phase. A full range of achiral stationary phases is available for use in SFC. The most common are silica, cyano, amino, and diol. Several relatively new phases, such as an ethyl pyridine phase, promise to decrease the need for additives in the mobile phase. Almost everything elutes from cyano columns. Diol and bare silica often give the best selectivity for acids and alcohols. Amino is often more retentive but also often yields the best selectivity for amines. Although any of these columns is likely to give a reasonable separation, the use of an automated column selection valve, along with a solvent selection valve, makes it easy to find the one with the best selectivity for a specific application. 

A chromatograph can employ a column selection valve (49) and a solvent selection valve with automation to empirically find the best column, and to a lesser extent, mobile phase, for a particular application. Samples are usually run overnight and the chromatograms evaluated in the morning. After the column giving the best separation is found, it usually only takes a few runs to further develop the method to the level needed for the separation goals. 

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