Recrystallisation

Single-solvent recrystallisation

Assuming that a suitable solvent is known, the first step in a recrystallisation is to dissolve the compound in the minimum amount of hot solvent. This is done by placing the compound in a conical flask, heating the solvent, and adding the hot solvent to the compound until it dissolves. The compound solution should also be kept hot, otherwise it will not stay in solution. At this stage, any insoluble impurities can be removed from the solution by hot filtration (see above). Soluble impurities remain in the solution. The hot solution is then covered (e.g. with a watchglass) and set aside to cool, at which point crystals of the compound should form. High-quality crystals are more likely to form if the rate of cooling is slow. Fast cooling, also known as “crash cooling”, can be attempted by securing the flask, containing the hot solution, in an ice bath; however, this is best avoided, as fast formation of crystals makes it likely that impurities from the solution will be trapped inside the crystals.


After the crystals have formed, the solution (sometimes called the “mother liquor”) contains the soluble impurities, and likely contains some of the compound as well, depending on its solubility. The crystals can be separated from the mother liquor by vacuum filtration. The crystals should be washed with a little cold solvent; this is to wash away traces of the mother liquor and the soluble impurities, without redissolving the compound. It is sometimes desirable to obtain successive crops of crystalline product from the mother liquor, by concentrating the filtrate and recrystallising again. These subsequent crops of crystals are usually less pure than the first crop, since the soluble impurities are also concentrated in the mother liquor; the crystals can be further purified by recrystallisation from fresh solvent.


Flow-chart for recrystallisation

Flowchart describing the process of recrystallisation taking an impure compound through to crystals of a pure compound.

Typical experimental procedure

Heat a conical flask containing solvent to boiling

Conical flasks should be used as this reduces the solvent loss as the sides of the conical should condense vapours reducing evaporation. Conical flasks should typically only be filled to around ¼ depth as this minimises the chance of solutions boiling out of the flask. Heating should be carried out with care so that solutions are just boiling and not allowed to boil vigorously which will generate large vapour clouds which could potentially be flammable.


Take crude compound in a conical flask

The crude compound should be placed into a conical flask ready for recrystallisation. Add a small amount of the hot recrystallisation solvent and swirl the flask to turn it into a paste before heating up the recrystallisation conical flask. There needs to be sufficient solvent in the flask to ensure that the compound doesn't melt from the direct heat of the hotplate, without adding too much solvent that the compound would fully dissolve before the solution is boiling.


Add solvent dropwise until all the solid is dissolved

Further portions of hot solvent should be added via Pasteur pipette to the recrystallisation flask until all the solid has just dissolved, assuming there are no insoluble impurities present (if there are in soluble impurities present, then should be removed via hot filtration).


Remove from heat and allow the flask to cool slowly

Flasks should be allowed to cool gradually without being disturbed as this enables the best possible crystal growth. Avoid moving the flask whilst it cools.


Cool further in ice

Once the flask has cooled slowly to room temperature it may be possible to encourage further growth by cooling in ice. Howver this may also cause some impurties to come out of solution.


Collect via filtration

Crystals should be filtered to collect. Usually a sinter is used for this purpose, although other filtration methods may also be appropriate.


Wash with ice-cold solvent

Crystals should be washed to remove any impurities from the surface of the crystals. Washing can also aid getting the crystals out of the conical flask and into the funnel. Solvent should generally be ice-cold to minimise redissolving the compound. Depending on the recrystallisation, the washing solvent might be the same as the recrystallisation solvent, only the anti-solvent, something else entirely or there may be multiple washes. An example might be from a water/ethanol recrystallisation where a water misible solvent would be used initially to wash crystals (eg ethanol) and then the crystals could be rewashed in another, typically more volatile solvent (eg diethyl ether).


There are a number of ways to wash crystals to ensure that impurities or non-volatile solvents are removed. One of the most effective is:



This may be repeated a few times to ensure the crystals are properly washed.


Dry crystals and collect

Crystals can be dried in a number of ways. Common options include:


Sucking air through the crystals following the washing stage is often a convinient way of drying crystals, especially where the solvents are very volatile. This usually minimises the loss of any solvents of crystallisation within the crystal structure.

Pressing crystals between filter paper can draw out some solvent and allow crystals to dry. However this is rarely useful alone and usually requires an additional form of drying.

Crystals can be allowed to dry by spreading them out on a watch glass and allowing evaporation to occur naturally. This runs the risk of contamination if the watch glass is not protected. Consideration should be given to the solvent evaporating (ventillation may be required).

Collecting the crystals into a round bottom flask, attaching a right angle adapter and connecting to a vacuum line. This will evaporate any residual solvent from the crystals and usually results in a compound without trace solvent impurities. However this method can sometimes damage the crystal structure by removing solvents of crystallisation from the structure.

Crystals can be placed on a watch glass inside a dessicator with a suitable dessicant. Over time the dessicant will absorb any solvent which is evaporating from the crystals.

A similar process to drying in vacuum, but allows crystals to be spread out on a watch glass whilst placed under vacuum.

An oven may be used to evaporate any residual solvent from the crystals. However common issues may include melting the compound and driving off solvent of recrystallisation. Compounds need to be spread out to dry effectively and compounds become prone to contamination in ovens or being distrubed by air currents and solvent vapours should be considered, eg they may present a fire risk.