Recrystallisation techniques

Solid organic compounds when isolated from organic reactions are seldom pure they are usually contaminated with small amounts of other compounds (impurities) which are produced along with the desired product. The purification of impure crystalline compounds is usually effected by crystallisation from a suitable solvent or mixture of solvents. 

The purification of solids by crystallisation is based upon differences in their solubility in a given solvent or mixture of solvents. In its simplest form, the crystallisation process consists of (i) dissolving the impure substance in some suitable solvent at or near the boiling point (ii) filtering the hot solution from particles of insoluble material and dust (iii) allowing the hot solution to cool 

The most desirable characteristics of a solvent for recrystallisation are as follows  

A high solvent power for the substance to be purified at elevated temperatures and a comparatively low solvent power at the laboratory temperature or below. 

It should dissolve the impurities readily or to only a very small extent. 

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To gain experience in recrystallisation technique the student should carry out the following experiments. 

In principle, there are a variety of routes to generate a desirable form of magnesium hydroxide. These range from milling of naturally occurring forms, such as bmcite, to precipitation and recrystallisation techniques. The target or guide is the property envelope of a typical finely precipitated ATH as shown in Table 4.2. 

The technique of recrystallisation from mixed solvents is as follows ... 

Residual traces of these impurities must thus be removed by some technique such as recrystallisation from chlorobenzene or acqueous alcohol. The melting point is a useful measure of purity and for polycarbonate resins the melting point should be in the range 154-157°C compared with values of 140-150°C for epoxy resin grade bis-phenol A. 

Much of the difficulty in demonstrating the mechanism of breakaway in a particular case arises from the thinness of the reaction zone and its location at the metal-oxide interface. Workers must consider (a) whether the oxide is cracked or merely recrystallised (b) whether the oxide now results from direct molecular reaction, or whether a barrier layer remains (c) whether the inception of a side reaction (e.g. 2CO - COj + C)" caused failure or (d) whether a new transport process, chemical transport or volatilisation, has become possible. In developing these mechanisms both arguments and experimental technique require considerable sophistication. As a few examples one may cite the use of density and specific surface-area measurements as routine of porosimetry by a variety of methods of optical microscopy, electron microscopy and X-ray diffraction at reaction temperature of tracer, electric field and stress measurements. Excellent metallographic sectioning is taken for granted in this field of research. 

The student should read Sections 11,27-11,31 where the technique of the recrystallisation of solids and cognate processes is described. To gain experience, he should carry out the following experiments. 

Supercritical C02 extraction coupled with a fractional separation technique is used by producers of flavours and fragrances to separate and purify volatile flavour and fragrance concentrates. Like any solvent, supercritical C02, it allows processing chemicals by predpita-tion or recrystallisation, obtaining partides of controlled size and shape, without excessive fines without thermal stresses and controlling the shape of a polymorphic substance. 

Retrogradation is another important property of starch. It is generally accepted that retrogradation is involved in the staling of baked products such as bread. In particular it appears that retrogradation is the recrystallisation of the amylopectin present. Notably, retrogradation is still a subject of research. The application of techniques such as 13C NMR allows insights that older techniques do not provide. 

Recrystallisation is a technique used to purify an impure solid. You may have used this technique to purify an impure sample of benzoic acid. 

The impure aspirin sample was then purified by recrystallisation from ethanol. Describe the steps the chemist would need to take to purify the aspirin sample using this technique. 

In these types of isotopic analysis, the same compound as that to be measured is used (element or molecule) where one of the atoms in it has been replaced by a radioisotope to allow radioactivity measurements. A small, precisely known quantity of the labelled compound, called the tracer, is added to the sample and, after homogenisation, an aliquot of the spiked sample is isolated by a fractionation technique such as recrystallisation or chromatography. The specific activity of the tracer is measured before and after fractionation. 

The technique for the removal of solids by filtration with suction has already been described (Section 2.19). The same technique will of course be applied to the collection of recrystallised compounds. Additionally, however, it should be noted that the mother-liquor from a recrystallisation is often of value for the recovery of further quantities of product, and should be transferred to another vessel after the crystals have been drained and washed with solvent. The mother-liquor may be then subsequently concentrated (Section 2.24 suitable precautions being taken, of course, if the solvent is flammable), and a further crop of crystals obtained. Occasionally yet another crop may be produced. The crops thus isolated are generally less pure than the first crystals which separate, and they should be combined and recrystallised from fresh solvent the purity is checked by a melting point determination. 

This technique is necessary either when the solubility of the compound in the requisite solvent is too high at ordinarily obtained temperatures (refrigerator to room temperatures) for recovery to be economic, or when handling compounds which are liquid at room temperature but which may be recrystallised from a solvent maintained at much lower temperatures (say —10 to — 40 °C). In this latter case, after several successive low temperature recrystallisations, the compound will revert to a liquid on storage at room temperature, but the purification process by recrystallisation will have been achieved. 

The student in the later stages of his training will certainly be required to recrystallise quantities of solid material within the range of 1 g to fractions of a milligram. These small quantities could arise from (i) small-scale preparations involving very expensive materials (ii) preparations of derivatives of small amounts of natural products (iii) by-products isolated from a reaction process (iv) chromatographic separation procedures (column and thin-layer techniques), etc. For convenience the experimental procedure to be adopted for recrystallisation of small quantities may be described under three groups ... 

Where a recrystallisation has been conducted in a centrifuge or small diameter tube and too much solvent has been added initially, concentration of the solution may be effected by the following technique. A small carborundum chip is introduced and the tube is heated very carefully over a water or oil bath of suitable temperature to give gentle boiling. A flow of nitrogen is directed to the surface of the boiling liquid by means of a capillary-end pipette the process is continued until the required concentration is effected. The technique of concentration may also be used in those cases where further crystalline crops are required from the mother-liquor. 

In general preparative work, the chromatographic techniques cited above may be used (a) to establish the purity and authenticity of starting materials and (if appropriate) reagents (b) to monitor the reaction, particularly in the case of new reactions, or in the optimisation of experimental conditions to achieve the highest possible yield of product (c) to check the isolation and purification procedures (d) to achieve the separation of product mixtures should this not be possible by means of distillation, recrystallisation, or sublimation procedures (e) to provide a further check on the authenticity of the final product in addition to that provided by the comparison of physical constants (e.g. m.p., b.p., d, [a]n, etc.) and spectroscopic data with those quoted in the literature. 

Secondly, the description of the general procedures given below, as distinct from the specific experimental procedures of the preparations described in earlier chapters, provides an excellent opportunity for the student to explore on the small scale the optimum reaction conditions, the chromatographic monitoring of the reaction, the methods of isolation and purification procedures (solvent extraction, recrystallisation, etc.) for the successful completion of the preparation. The small-scale nature of the experiments is of particular importance in providing experience of those techniques of reaction work-up in which mechanical loss is frequently the reason for failure. Such experience is vital to the synthetic chemist since many of the new chemo-, regio- and stereo-specific reagents are expensive and used in small-scale reactions. 

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