Recrystallization is a method used to purify chemicals by dissolving a mixture of a compound and its impurities, in an appropriate solvent, prior to heating the solution. Following the dissolution of crude product, the mixture will passively cool, yielding a crystallized compound and its impurities as separate entities. The newly formed crystals can then be subjected to x-ray anaylsis for purity assessment.

Methods

Single-solvent recrystallization

The solvent utilized in single-solvent recrystallization must dissolve the crude reaction mixture only when it is heated to reflux. The heated solution is then passively cooled, yielding a crystallized product absent of impurities. The solid crystals are then collected utilizing a filtration apparatus and the filtrate is discarded. Product purity can then be assessed via NMR spectroscopy.

Multi-solvent recrystallization

Multi-solvent recrystallization relies on the crude product being soluble in one solvent, when it is heated to reflux, while being insoluble in a secondary solvent, regardless of the solvent's temperature. The volume ratio between the first and second solvent is critical. A higher ratio of first to second solvent will lead to permanent dissolution of the desired product, while a low ratio will lead to minimal pure crystal recovery. The terms first and second are in reference to crude product soluble and crude product insoluble solvents respectively. Typically, the second solvent, following the dissolution of the impure solid in the first solvent, is added slowly until the desired product begins to crystallize from solution. The solution is then cooled to further induce recrystallization.

Hot filtration recrystallization

Hot filtration recrystallization can be used to separate a pure compound from both impurities and some insoluble matter, which may be anything from a third party impurity to fragments of broken glass. The technique makes use of the single solvent system, outlined above, by dissolving a crude reaction mixture, in a minimum amount of hot solvent, before gravity filtering the saturated solution to remove insoluble matter. The saturated solution will then passively cool, yielding pure crystals.

X-ray analysis

Recrystallized products are often subject to X-ray crystallography for purity assessment. The technique requires crystalized products to be singular, and absent of clumps. Several approaches to this phenomena are listed below.

[→ Solvent added (clear) to compound (orange) to give compound solution (orange) → The second solvent added (blue) to the compound solution (orange) to give mixed solvent system (green)

→ Vessel sealed but a small hole allows solvent vapour (clear) to slowly evaporate over time to give crystals (orange) and a saturated mixed solvent solution (blue-green). | upload.wikimedia.org/wikipedia/commons/2/22/x-ray///crystals///-///slow///evaporation///2///solvent.png]

[→ Solvent added (clear) to compound (orange) in the first vessel to give compound solution (orange) → The first vessel is placed in a second vessel contain second solvent (blue). The second vessel is sealed, and the first vessel is also sealed, although a small hole in the first vessel is present. This hole allows volatile solvent vapour (blue) to slowly evaporate from the second vessel and condensate (that is infuse) into the first vessel, to give a mixed solvent system (green)

→ Over time this gives crystals (orange) and a saturated mixed solvent system (green-blue). | upload.wikimedia.org/wikipedia/commons/0/01/x-ray///crystals///-///slow///gas///diffusion///2///solvent.png]

[→ Solvent added (clear) to compound (orange) to give compound solution (orange) → The second solvent added (blue) carefully so that the two solvents do not mix.

→ The two solvents mix (diffuse) slowly over time to give crystals (orange) at the solvent interface (green) | upload.wikimedia.org/wikipedia/commons/3/32/x-ray///crystals///-///slow///liquid///diffusion.png]

[→ Solvent added (clear) to compound (orange) to give a compound solution (orange)

→ The second solvent added (blue) to the second tube chamber → The two solvents mix slowly over time, the mixing is slowed by a fine sinter separating the two solvent chambers, to give crystals (orange) at the solvent interface (green) over time | upload.wikimedia.org/wikipedia/commons/2/27/x-ray///crystals///-///slow///liquid///diffusion///-///H///Tube.png]