Recrystallisation

Solvents commonly used for recrystallisation, and their boiling points, are given in Table 7. 

For comments on the toxicity and use of benzene see the first pages of Chapters 4, 5 and 6. 

Mixed Solvents. Where a substance is too soluble in one solvent and too insoluble in another, for either to be used for recrystallisation, it is often possible (provided they are miscible) to use them as a mixed solvent. (In general, however, it is preferable to use a single solvent if this is practicable.) Table 8 contains many of the common pairs of miscible solvents. 

The technique of recrystallisation from mixed solvents is as follows  

The material is dissolved in the solvent in which it is the more soluble, then the other solvent (heated to near boiling) is added cautiously to the hot solution until a slight turbidity persists or crystallisation begins. This is cleared by adding several drops of the first solvent, and the solution is allowed to cool and crystallise in the usual way. 

Suppose you have carried out a chemical reaction and the product and the starting material are both solids. If the reaction has gone to completion and you have no starting material remaining, then it may be quite pure. But the probability is that the product will contain some impurities, perhaps even a lot of starting material. How do you separate the compound you want from the others present Recrystallisation is a routine technique for doing this. It is used for purifying a crystalline solid which contains fairly small amounts of impurities. 

First choose your solvent. The choice of solvent is crucial. You need a solvent in which your chosen compound is only slightly soluble when cold, but very soluble when the solvent is hot. In addition, the impurities present must be either completely insoluble in the solvent, both cold or hot, or stay dissolved in the solvent even when it is cold. The solvents that are required for purifying specific mixtures are often mixtures of two or three components in set proportions. 

1 You will need a supply of hot solvent and a hot flask (usually a conical flask) with a hot funnel and a folded filter paper. 

3 Some impurities may not be soluble in the solvent. If this is the case. 

If the solution is coloured because of other impurities, it can be cleaned up using a small amount of decolourising charcoal. Add this to the solution, shake, and again filter through a hot funnel to remove the charcoal. 

Filtration removes particulate impurities rapidly from liquids and is also used to collect insoluble or crystalline solids which separate or crystallise from solution. The usual technique is to pass the solution, cold or hot, through a fluted filter paper in a conical glass funnel (see Vogel s Textbook of Practical Organic Chemistry, p 46). 

Freeing a solution from extremely small particles (e.g. for ORD or CD measurements) requires filters with very small pore size. Commercially available (Millipore, Gelman, Nucleopore) filters other than cellulose or glass include nylon. Teflon, and polyvinyl chloride, and the pore diameter may be as small as 0.01 micron (see Table 4). Special containers are used to hold the filters, through which the solution is pressed by applying pressure, e.g. from a syringe. Some of these filters can be used to clear strong sulphuric acid solutions.  

As an alternative to the Buchner funnel for collecting crystalline solids, a funnel with a sintered glass-plate under suction may be used. Sintered-glass funnels with various porosities are commercially available and can easily cleaned with warm chromic or nitric acid (see above). 

The best solvents for recrystallisation have the following properties  

The following generalisations provide a rough guide to the selection of a suitable solvent  

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Filtration. Before discussing the practical details of the purification of solid substances by recrystallisation, it is convenient to describe here the general methods of filtration. The two principal occasions in organic chemistry when filtration is necessary are ... 

Recrystallisation. The process of purification by recrystallisation is undoubtedly the most frequent operation in practical organic chemistry, and it is one which, when cleanly and efficiently performed, should give great pleasure to the chemist, particularly if the original crude material is in a very impure and filthy condition. Yet no operation is carried out so badly, wastefully (and thoughtlessly) by students in general, not only by elementary students, but often by research students of several years experience. The student who intends later to do advanced work must master the process, for unless he can choose a suitable solvent and then successfully recrystallise often minute quantities of material, he will frequently find his work completely arrested. 

Students are sometimes puzzled at the extraordinarily general application of the process of recrystallisation, since it may appear to them to depend on the assumption that the impurities are more soluble than the... 

It is clear that repeated recrystallisation will rapidly leave B entirely in the mother-liquors, and thus provide a pure sample of A. 

The choice of a solvent is of course determined primarily by its suitability for the actual recrystallisation of the given crude product. If two or more solvents appear to be almost equally suitable for the recrystallisation, the final choice should depend on the inflammability (and therefore risk in use) of the solvent, and also on its cost. It is assumed that a solvent which might have any chemical action on the compound has already been debarred. The chief solvents normally available are ... 

Carbon disulphide should never be used if any alternative solvent is available, as it has a dangerously low flash-point, and its vapours form exceedingly explosive mixtures with air. Ether as a solvent for recrystallisation is much safer than carbon disulphide, but again should be avoided whenever possible, partly on account of the danger of fires, and partly because the filtered solution tends to creep up the walls of the containing vessel and there deposit solid matter by complete evaporation instead of preferential crystallisation. 

Repetition of Recrystallisation on Larger Scale. Having now determined both the best solvent and also the approximate... 

If a compound has been recrystallised from petrol, benzene, etc.y some freshly cut shavings of clean paraffin wax should be added to the calcium chloride in (A) or to the sodium hydroxide in D, The surface of the wax absorbs organic solvent vapours (particularly the hydrocarbons) and the last trace of such solvents is thus readily removed from the recrystallised material. 

Checking the Purification. The purity of the dry re-crystallised material must now be determined, as it is possible that repeated recrystallisation may be necessary to obtain the pure material. The purity is therefore checked by a melting-point determination, and the recrystallisation must be repeated until a sharp melting-point is obtained. Should the compound have no well-defined melting-point e.g.y the salt of an organic acid or base), it must be analysed for one suitable component element, until its analysis agrees closely with that theoretically required. 

Experiment 4. Choice of Solvent and Complete Recrystallisation. Students should be supplied with distilled water and with the more common organic solvents, and also with the compounds mentioned below. Taking each compound in turn they should decide, by the methods described in (i) above, which of these six solvents is the best for recrystallisation. They should then recrystallise about 5 g. of at least two of the compounds, dry the product, and whenever possible take its melting-point. 

Decolorisation by Animal Charcoal. It sometimes hap pens (particularly with aromatic and heterocyclic compounds) that a crude product may contain a coloured impurity, which on recrystallisation dissolves in the boiling solvent, but is then partly occluded by crystals as they form and grow in the cooling solution. Sometimes a very tenacious occlusion may thus occur, and repeated and very wasteful recrystallisation may be necessary to eliminate the impurity. Moreover, the amount of the impurity present may be so small that the melting-point and analytical values of the compound are not sensibly affected, yet the appearance of the sample is ruined. Such impurities can usually be readily removed by boiling the substance in solution with a small quantity of finely powdered animal charcoal for a short time, and then filtering the solution while hot. The animal charcoal adsorbs the coloured impurity, and the filtrate is usually almost free from extraneous colour and deposits therefore pure crystals. This decolorisation by animal charcoal occurs most readily in aqueous solution, but can be performed in almost any organic solvent. Care should be taken not to use an excessive quantity... 

Animal charcoal has a further use. Occasionally, when recrystallising a crude product, it is found that the hot solutioi contains a very fine suspension of an insoluble impurity. This suspension may be so fine... 

The ethereal extracts are then united, dried with a suitable drying agent and filtered. The filtrate is then cautiously distilled, the ether being first distilled and finally the organic compound if volatile if the compound is solid, the crude residue is purified by recrystallisation. Very great care must be taken on all occasions when ether is distilled because of the risk of fire or of an explosion full experimental details for this operation are given, both on p. 8o (Preparation of Ether) and on p. 164 (Pre-... 

When the correct solvent for recrystallisation is not known a procedure similar to that given on pp. 15-16 should be followed, but on the semi-micro scale not more than 10 mg. of the solid should be placed in the tapered-end test-tube (Fig. 29(B)) and about o i ml. of the solvent should be added from the calibrated dropping-pipette (Fig. 30(B)). If the compound dissolves readily in the cold, the solvent is unsuitable, but the solution should not be discarded. [In this case recourse should be had to the use of mixed solvents (p. 18). For example if the substance is very soluble in ethanol, water should be added from a calibrated pipette with shaking to determine whether crystallisation will now take place, indicated by a cloudiness or by the separation of solid.]... 

If the solid does not dissolve in the cold solvent gently heat the mixture over a micro-Bunsen burner or in a small water-ba until the liquid boils. Continue to add o-i ml. portions of solvent until the solid dissolves. [If more than about i ml. of solvent is required, the solvent is considered unsatisfactory.] If a clear solution is obtained, cool the tube and scratch it below the surface of the solution with a very fine glass rod and proceed as suggested on p. 16. In general, the products from the choice of solvent investigation are not discarded but added to the main bulk of the crude product for recrystallisation. 

Drying of crystals. Whenever possible crystals should be dried in a smdl vacuum desiccator containing a suitable desiccant. The latter depends upon the nature of the solvent used c/. p. 19). However for most purposes anhydrous calcium chloride is satisfactory. If a hydrocarbon has been used in the recrystallisation, a few thin fresh shavings of paraffin wax are efficacious. 

Place 0 5 ml. of acetone, 20 ml. of 10% aqueous potassium iodide solution and 8 ml. of 10% aqueous sodium hydroxide solution in a 50 ml. conical flask, and then add 20 ml. of a freshly prepared molar solution of sodium hypochlorite. Well mix the contents of the flask, when the yellow iodoform will begin to separate almost immediately allow the mixture to stand at room temperature for 10 minutes, and then filter at the pump, wash with cold w ater, and drain thoroughly. Yield of Crude material, 1 4 g. Recrystallise the crude iodoform from methylated spirit. For this purpose, place the crude material in a 50 ml. round-bottomed flask fitted with a reflux water-condenser, add a small quantity of methylated spirit, and heat to boiling on a water-bath then add more methylated spirit cautiously down the condenser until all the iodoform has dissolved. Filter the hot solution through a fluted filter-paper directly into a small beaker or conical flask, and then cool in ice-water. The iodoform rapidly crystallises. Filter at the pump, drain thoroughly and dry. 

Impure aldehydes and ketones are sometimes purified by conversion into the corresponding oximes, and the latter after recrystallisation are then hydrolysed by boiling with dilute sulphuric acid ... 

The oxime is freely soluble in water and in most organic liquids. Recrystallise the crude dry product from a minimum of 60-80 petrol or (less suitably) cyclohexane for this purpose first determine approximately, by means of a small-scale test-tube experiment, the minimum proportion of the hot solvent required to dissolve the oxime from about 0-5 g. of the crude material. Then place the bulk of the crude product in a small (100 ml.) round-bottomed or conical flask fitted with a reflux water-condenser, add the required amount of the solvent and boil the mixture on a water-bath. Then turn out the gas, and quickly filter the hot mixture through a fluted filter-paper into a conical flask the sodium chloride remains on the filter, whilst the filtrate on cooling in ice-water deposits the acetoxime as colourless crystals. These, when filtered anddried (either by pressing between drying-paper or by placing in an atmospheric desiccator) have m.p. 60 . Acetoxime sublimes rather readily when exposed to the air, and rapidly when warmed or when placed in a vacuum. Hence the necessity for an atmospheric desiccator for drying purposes. 

Hydrolysis of Acetoxime. Place about i g. of the recrystallised oxime in a small distilling-flask (50 ml.), add 10 ml. of dilute HjSO, and heat gently until about half the solution has distilled over. Test [a] the aqueous distillate for acetone by the iodoform reaction (p.346), b) the residual solution in the distilling-flask for hydroxylamine by... 

One disadvantage of using acetic anhydride is that with primary amines, traces of the diacctyl compound, RN(COCH3)2, niay be formed the chances of this secondary acetylation are, however, usually remote, and recrystallisation from an aqueous solvent will generally hydrolyse the diacetyl derivative rapidly back to the mono-acetyl compound. 

Naphthyl Acetate. CHgCOOCi H,. Dissolve 1 g. of pure 2-naphtnol in 5 ml. (r8 mols.) of 10% sodium hydroxide solution as before, add 10 g. of crushed ice, and i-i ml. (1-14 g., 1 5 mols.) of acetic anhydride. Shake the mixture vigorously for about 10-15 minutes the 2-naphthyl acetate separates as colourless crystals. Filter at the pump, wash with water, drain, and dry thoroughly. Yield of crude material, 1-4 g. (theoretical). Recrystallise from petroleum (b.p. 60-80 ), from which, on cooling and scratching, the 2-naphthyl acetate separates as colourless crystals, m.p, 71 yield, 10 g. 

It should be emphasised that salicylic acid can be readily acetylated by Method 1, and that the above preparation of acetylsalicyclic acid is given solely as an illustration of Method 2. To employ Method 1, add 10 g. of salicylic acid to 20 ml. of a mixture of equal volumes of acetic anhydride and acetic acid, and boil gently under reflux for 30 minutes. Then pour into about 200 ml. of cold water in order to precipitate the acetylsalicylic acid (11 g.) and finally recrystallise as above. Method 2, however, gives the purer product. 

Add 5 g. of potassium hydrogen tartrate and 5 g. of antimony trioxide (each being finely powdered) to 30 ml. of water contained in a small flask, and boil the mixture under a reflux water-condenser for 15 minutes. Then filter hot, using a Buchner funnel and flask which have been preheated by the filtration of some boiling distilled water. Pour the clear filtrate into a beaker and allow to cool. Potassium antimonyl tartrate separates as colourless crystals. Filter, drain and dry. Yield, 5 g. The product can be recrystallised from hot water, but this is usually not necessary. 

Acetamide is thus obtained as a colourless crystalline solid, which has a characteristic odour of mice, stated to be due to the presence of small quantities of methylacetamide, CH3CONHCH3. The acetamide can be purified and rendered odourless by re-crystallisation from acetone, and then has m.p. 82°, b.p. 223°. If this recrystallisation is contemplated, the distilled material should be collected directly into a small weighed beaker or conical flask, so that the solidified acetamide can be readily broken up and removed. 

Succinamide. NHoCOCH2 CH2CONH2. (Method 2(a)). Add 5 ml. (5 8 g.) of dimethyl succinate to a mixture of 50 ml. of water and 25 ml. of concentrated [dy o-88o) aqueous ammonia solution in a 150 ml. conical flask. Cork the flask and shake the contents the dimethyl succinate rapidly dissolves to give a clear solution. Allow the solution to stand after about i hour the succinamide starts to crystallise, and then continues to separate for some time. Next day, filter off the succinamide at the pump, wash with cold water, and drain. Recrystallise from water, from which the succinamide separates as colourless crystals the latter soften at 240° and melt at 254 -255° with... 

Carry out this preparation in precisely the same way as the above preparation of oxamide, using 2 ml. (2-4 g.) of benzoyl chloride instead of the ethyl oxalate, and observing the same precautions. Considerably more heat is generated in this reaction therefore hold the cork very securely in position during the shaking. After vigorous shaking for 15 minutes, no trace of oily benzoyl chloride remains. Filter off the fine flakes of benzamide, wash with cold water, and then recrystallise from hot water yield, 1-5 g. Colourless crystals, m.p. 130°. 

Place I g. of benzamide and 15 ml. of 10% aqueous sodium hydroxide solution in a 100 ml. conical flask fitted with a reflux water-condenser, and boil the mixture gently for 30 minutes, during which period ammonia is freely evolved. Now cool the solution in ice-water, and add concentrated hydrochloric acid until the mixture is strongly acid. Benzoic acid immediately separates. Allow the mixture to stand in the ice-water for a few minutes, and then filter off the benzoic add at the pump, wash with cold water, and drain. Recrystallise from hot water. The benzoic acid is obtained as colourless crystals, m.p. 121°, almost insoluble in cold water yield, o 8 g. (almost theoretical). Confirm the identity of the benzoic acid by the tests given on p. 347. 

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