Recrystallization (chemistry)

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Crystallization
Process-of-Crystallization-200px.png
Fundamentals
Crystal  · Crystal structure  · Nucleation
Concepts
Crystallization  · Crystal growth
Recrystallization  · Seed crystal
Protocrystalline  · Single crystal
Methods and technology
Boules
Bridgman–Stockbarger method
Van Arkel–de Boer process
Czochralski method
Epitaxy  · Flux method
Fractional crystallization
Fractional freezing
Hydrothermal synthesis
Kyropoulos method
Laser-heated pedestal growth
Micro-pulling-down
Shaping processes in crystal growth
Skull crucible
Verneuil method
Zone melting

In chemistry, recrystallization is a technique used to purify chemicals. By dissolving a mixture of a compound and impurities in an appropriate solvent, either the desired compound or impurities can be removed from the solution, leaving the other behind. It is named for the crystals often formed when the compound precipitates out. Alternatively, recrystallization can refer to the natural growth of larger ice crystals at the expense of smaller ones.

Contents

Chemistry

In chemistry, recrystallization [1] :127–132 is a procedure for purifying compounds. The most typical situation is that a desired "compound A" is contaminated by a small amount of "impurity B". There are various methods of purification that may be attempted (see Separation process), recrystallization being one of them. There are also different recrystallization techniques that can be used such as:

Single-solvent recrystallization

Typically, the mixture of "compound A" and "impurity B" is dissolved in the smallest amount of hot solvent to fully dissolve the mixture, thus making a saturated solution. The solution is then allowed to cool. As the solution cools the solubility of compounds in the solution drops. This results in the desired compound dropping (recrystallizing) from the solution. The slower the rate of cooling, the bigger the crystals form.

- Solvent added (clear) to compound (orange) - Solvent heated to give saturated compound solution (orange) - Saturated compound solution (orange) allowed to cool over time to give crystals (orange) and a saturated solution (pale-orange). 1 solvent recrystallisation.png
→ Solvent added (clear) to compound (orange) → Solvent heated to give saturated compound solution (orange) → Saturated compound solution (orange) allowed to cool over time to give crystals (orange) and a saturated solution (pale-orange).
Crystallization of Ibuprofen in HCl(aq) Crystallization Ibuprofen Salt.JPG
Crystallization of Ibuprofen in HCl(aq)

In an ideal situation the solubility product of the impurity, B, is not exceeded at any temperature. In that case, the solid crystals will consist of pure A and all the impurities will remain in the solution. The solid crystals are collected by filtration and the filtrate is discarded. If the solubility product of the impurity is exceeded, some of the impurities will co-precipitate. However, because of the relatively low concentration of the impurity, its concentration in the precipitated crystals will be less than its concentration in the original solid. Repeated recrystallization will result in an even purer crystalline precipitate. The purity is checked after each recrystallization by measuring the melting point, since impurities lower the melting point. NMR spectroscopy can also be used to check the level of impurity. Repeated recrystallization results in some loss of material because of the non-zero solubility of compound A.

The crystallization process requires an initiation step, such as the addition of a "seed" crystal. In the laboratory, a minuscule fragment of glass, produced by scratching the side of the glass recrystallization vessel, may provide the nucleus on which crystals may grow. Successful recrystallization depends on finding the right solvent. This is usually a combination of prediction/experience and trial/error. The compounds must be more soluble at higher temperatures than at lower temperatures. Any insoluble impurity is removed by the technique of hot filtration.

Multi-solvent recrystallization

This method is the same as the above but where two (or more) solvents are used. This relies on both "compound A" and "impurity B" being soluble in a first solvent. A second solvent is slowly added. Either "compound A" or "impurity B" will be insoluble in this solvent and precipitate, whilst the other of "compound A"/"impurity B" will remain in solution. Thus the proportion of first and second solvents is critical. Typically the second solvent is added slowly until one of the compounds begins to crystallize from the solution and then the solution is cooled. Heating is not required for this technique but can be used.

- Solvent added (clear) to compound (orange) - Solvent heated to give saturated compound solution (orange) - Second solvent (blue) added to the compound solution (orange) to give a mixed solvent system (green) - Mixed solvent system (green) allowed to cool over time to give crystals (orange) and a saturated mixed solvent system (green-blue). 2 solvent recrystallisation.png
→ Solvent added (clear) to compound (orange) → Solvent heated to give saturated compound solution (orange) → Second solvent (blue) added to the compound solution (orange) to give a mixed solvent system (green) → Mixed solvent system (green) allowed to cool over time to give crystals (orange) and a saturated mixed solvent system (green-blue).

The reverse of this method can be used where a mixture of solvents dissolves both A and B. One of the solvents is then removed by distillation or by an applied vacuum. This results in a change in the proportions of the solvent causing either "compound A" or "impurity B" to precipitate.

- First solvent added (clear) to compound (orange) - Solvent heated to give saturated compound solution (orange) - Second solvent (blue) added to the compound solution (orange) to give the first mixed solvent system (green) - Volatile first solvent (clear) is removed (e.g. evaporation) from the first mixed solvent system (green) to give a second mixed solvent system (dark green) - Second mixed solvent system (dark-green) allowed to cool over time to give crystals (orange) and a saturated second mixed solvent system (green-blue). 2 solvent recrystallisation with evaporation.png
→ First solvent added (clear) to compound (orange) → Solvent heated to give saturated compound solution (orange) → Second solvent (blue) added to the compound solution (orange) to give the first mixed solvent system (green) → Volatile first solvent (clear) is removed (e.g. evaporation) from the first mixed solvent system (green) to give a second mixed solvent system (dark green) → Second mixed solvent system (dark-green) allowed to cool over time to give crystals (orange) and a saturated second mixed solvent system (green-blue).

Hot filtration-recrystallization

Hot filtration [1] :74 can be used to separate "compound A" from both "impurity B" and some "insoluble matter C". This technique normally uses a single-solvent system as described above. When both "compound A" and "impurity B" are dissolved in the minimum amount of hot solvent, the solution is filtered to remove "insoluble matter C". This matter may be anything from a third impurity compound to fragments of broken glass. For a successful procedure, one must ensure that the filtration apparatus is hot in order to stop the dissolved compounds from crystallizing from the solution during filtration, thus forming crystals on the filter paper or funnel.

One way to achieve this is to heat a conical flask containing a small amount of clean solvent on a hot plate. A filter funnel is rested on the mouth, and hot solvent vapors keep the stem warm. Jacketed filter funnels may also be used. The filter paper is preferably fluted, rather than folded into a quarter; this allows quicker filtration, thus less opportunity for the desired compound to cool and crystallize from the solution.

Often it is simpler to do the filtration and recrystallization as two independent and separate steps. That is dissolve "compound A" and "impurity B" in a suitable solvent at room temperature, filter (to remove insoluble compound/glass), remove the solvent and then recrystallize using any of the methods listed above.

- Solvent added (clear) to a mixture of compound (orange) + insoluble substance (purple) - Solvent heated to give saturated compound solution (orange) + insoluble substance (purple) - Saturated compound solution (orange) filtered to remove insoluble substance (purple) - Saturated compound solution (orange) allowed to cool over time to give crystals (orange) and a saturated solution (pale-orange). Hot-filtration 1 solvent recrystallisation.png
→ Solvent added (clear) to a mixture of compound (orange) + insoluble substance (purple) → Solvent heated to give saturated compound solution (orange) + insoluble substance (purple) → Saturated compound solution (orange) filtered to remove insoluble substance (purple) → Saturated compound solution (orange) allowed to cool over time to give crystals (orange) and a saturated solution (pale-orange).

Seeding

Crystallization requires an initiation step. This can be spontaneous or can be done by adding a small amount of the pure compound (a seed crystal) [1] to the saturated solution, or can be done by simply scratching the glass surface to create a seeding surface for crystal growth. It is thought that even dust particles can act as simple seeds.

Single perfect crystals (for X-ray analysis)

Growing crystals for X-ray crystallography can be quite difficult. For X-ray analysis, single perfect crystals are required. Typically a small amount (5–100 mg) of a pure compound is used, and crystals are allowed to grow very slowly. Several techniques can be used to grow these perfect crystals:

- Solvent added (clear) to compound (orange) to give compound solution (orange) - Vessel sealed but a small hole allows solvent vapour (clear) to slowly evaporate from compound solution (orange) over time to give crystals (orange) and a saturated solution (pale-orange). X-ray crystals - slow evaporation 1 solvent.png
→ Solvent added (clear) to compound (orange) to give compound solution (orange) → Vessel sealed but a small hole allows solvent vapour (clear) to slowly evaporate from compound solution (orange) over time to give crystals (orange) and a saturated solution (pale-orange).
- 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). X-ray crystals - slow evaporation 2 solvent.png
→ 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).
- 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). X-ray crystals - slow gas diffusion 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).
- 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) X-ray crystals - slow liquid diffusion.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)
- 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 X-ray crystals - slow liquid diffusion - H Tube.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

Ice

For ice, recrystallization refers to the growth of larger crystals at the expense of smaller ones. Some biological antifreeze proteins have been shown to inhibit this process, and the effect may be relevant in freezing-tolerant organisms. [2]

See also

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References

  1. 1 2 3 Harwood, Laurence M.; Moody, Christopher J. (1 January 1990). Experimental Organic Chemistry: Principles and Practice (Illustrated ed.). Blackwell Scientific Publications. ISBN   978-0-632-02016-4. LCCN   88007680. OCLC   18816225. OL   2032038M. Wikidata   Q107313989 . Retrieved 2021-06-22 via Internet Archive.
  2. Kumar Verma, Ashok (2014). "Recrystallization of Ice". Encyclopedia of Snow, Ice and Glaciers. Encyclopedia of Earth Sciences Series. p. 932. doi:10.1007/978-90-481-2642-2_439. ISBN   978-90-481-2641-5.

Reference books