Recrystallization solvent selection

Successful recrystallization of an impure solid is usually a function of solvent selection. The ideal solvent, of course, dissolves a large amount of the compound at the boiling point but very little at a lower temperature. Such a solvent or solvent mixture must exist (one feels) for the compound at hand, but its identification may necessitate a laborious trial and error search. Solvent polarity and boiling point are probably the most important factors in selection. Benzhydrol, for example, is only slightly soluble in 30-60 petroleum ether at the boiling point but readily dissolves in 60-90° petroleum ether at the boiling point. 

Until one develops a feel for recrystallization, the best procedure for known compounds is to duplicate a selection in the literature. For new compounds, a literature citation of a solvent for an analogous structure is often a good beginning point. To assist in the search, Table A3.4 lists several of the common recrystallizing solvents with useful data. The dielectric constant can be taken to be a rough measure of solvent polarity. 

Trial and error is usually required in selecting a second solvent for a mixture. There are some generally successful mixtures, such as diethyl ether/methanol (or ethanol) for highly associated solids (especially amides and alcohols) and many natural products, and diethyl ether/petroleum ether (or benzene) for dipolar compounds (especially esters and alcohols) and hydrocarbons . Cf. also J. B. Baumann Solvent Selection for Recrystallization. J. Chem. Educ. 56, 64 (1979) R. E. R. Craig Rapid, Efficient Determination of Recrystallization Solvents at the Microscale Level, J. Chem. Educ. 66, 88 (1989). 

Both normal and the much smaller semi-micro test tubes are used for small-scale reactions and tests, e.g. qualitative analysis (p. 135) or solvent selection for recrystallization (p. 93). 

To find a suitable solvent for recrystallization you must carry out a series of tests measuring the solubility of your crude compound in a series of solvents (cold and hot) of varying solvent polarity. This series of tests is called solvent selection and is carried out on a test tube scale but, as your technique improves, you can carry out the tests using semi-micro scale since you will use less of your compound during the process. The procedure for solvent selection at the test tube scale is described in Box 13.1 and modification of the procedure to semi-micro scale requires only a corresponding reduction of the quantities of solvent and solute used. 

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

To carry out a single-solvent recrystallization (Box 13.3) you must get the compound into solution and this is achieved by suspending it in the appropriate cold solvent, found in the solvent selection process, and then heating the mixture to dissolve the soUd. The equipment used will depend on the boiling point of the solvent, its flammability and toxicity. Some general systems are shown in Table 13.2. 

It is important to remember that for a successful recrystallization, you need to use equipment of a size appropriate to the amount of solid and the volume of solvent you are likely to use. You can estimate the volume of solvent to be used by extrapolation of the data from your solvent selection tests. In general terms, conical flasks, beakers and round-bottom flasks should never be more than half-full of solution but, on the other hand, using small volumes of solutions in large flasks will result in losses of the compound on the sides of the vessels. 

Since crystalline compounds sometimes show polymorphism depending on the crystallization method, i.e., whether vapor phase or liquid phase, on the growing rate of crystals, and on the solvent used for recrystallization, proper selection of the crystallization conditions is necessary. For example, 4-pyrrolidino-3-(A-(acetyl)amino)nitrobenzene (PAN) was found to give SHG-active crystals by rapid recrystallization and SHG-inactive crystals by slow growth of crystals. ... 

By way of contrast, irradiation for 6 h in the solid state of the 1 2 inclusion complex 12a composed of 1 and 11a which has been prepared by recrystallization of the two components from a solvent gave the syn-head-to-tail dimer 13a selectively in 90% yield 7,8>. Similar irradiation of the 1 2 inclusion complexes 12b-12d composed of 1... 

Gas [Gas anti-solvent] A process for separating dissolved materials by selective precipitation with added supercritical carbon dioxide. First used for recrystallizing the explosive RDX subsequently used for recrystallizing other explosives, pharmaceuticals, fine chemicals, and food products. 

In practice, diarylide yellow pigments are frequently selected for their excellent fastness to a variety of organic solvents, in which they perform much better than monoazo yellow pigments. Properties such as migration or recrystallization... 

Crystallization is often used as a method of product isolation. Crystallization of the reaction product may be induced if, to the reaction medium, in which it is well soluble, a cosolvent is added in which the product is insoluble. Because for the latter purification method the solubility should be high at high temperatures but much lower at low temperatures, the temperature coefficient of the solubility becomes an important criterion for the employment of a solvent. A further guide is the fact that substances tend to dissolve in solvents with similar polarities, so that a solvent and cosolvent for the recrystallization of a given product can be selected according to the polarities. 

If both anomers of the glycoside are obtained in a reaction, it is necessary to separate them. One separation method that has been used is the preferential extraction101 of the anomers with a volatile solvent. After extraction of the individual glycoside, the solvent is removed by evaporation, and the glycoside may be obtained in crystalline form. A second method of separation utilizes fractional recrystallization, and it may be possible by proper selection of the solvent to obtain both anomers in crystalline form. A third method utilizes chromatography for separating the anomers, and the pure anomers may be obtained from appropriate fractions from the column. The anomeric configuration of the anomers which have been obtained in pure form will need to be determined. Such determinations can be made by measurement of physical constants, from the n.m.r. spectra, and from the susceptibility of the anomer to enzymes of known specificity. 

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