In chemistry, recrystallization is a technique used to purify chemicals. By dissolving both impurities and a compound 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.
Chemistry
In chemistry, recrystallization 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, 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 solution drops. This results in the desired compound
dropping (recrystallizing) from 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).
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 impurity will
remain in 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 impurity 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 the higher temperature than at the
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 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
compound solution (orange) to give 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 solvent
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 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 compound solution (orange) to give first mixed solvent system
(green) → Volatile first solvent (clear) is removed (e.g. evaporation)
from 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
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 crystallizing from 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).
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) 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 pure compound is used,
and crystals are allowed to grow very slowly. Several techniques can be
used to grow these perfect crystals:
- Slow evaporation of a single solvent - typically the compound is dissolved in a suitable solvent and the solvent is allowed to slowly evaporate. Once the solution is saturated crystals can form.
→
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).
- Slow evaporation of a multi-solvent system - the same as above, however as the solvent composition changes due to evaporation of the more volatile solvent. The compound is more soluble in the volatile solvent, and so the compound becomes increasingly insoluble in solution and crystallizes.
→
Solvent added (clear) to compound (orange) to give compound solution
(orange) → Second solvent added (blue) to 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).
- Slow diffusion - similar to the above. However, a second solvent is allowed to evaporate from one container into a container holding the compound solution (gas-diffusion). As the solvent composition changes due to an increase in solvent that has gas-diffused into solution, the compound become increasingly insoluble in solution and crystallizes.
→
Solvent added (clear) to compound (orange) in first vessel to give
compound solution (orange) → First vessel is placed in a second vessel
contain second solvent (blue). The second vessel is sealed, 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 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).
- Interface/slow mixing (often performed in an NMR tube). Similar to the above, but instead of one solvent gas-diffusing into another, the two solvents mix (diffuse) by liquid-liquid diffusion. Typically a second solvent is "layered" carefully on top of the solution containing the compound. Over time the two solution mix. As the solvent composition changes due to diffusion, the compound becomes increasingly insoluble in solution and crystallizes, usually at the interface. Additionally, it is better to use a denser solvent as the lower layer, and/or a hotter solvent as the upper layer because this results in the slower mixing of the solvents.
→
Solvent added (clear) to compound (orange) to give compound solution
(orange) → 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 solvent interface (green)
- Specialized equipment can be used in the shape of a "H" to perform the above, where one of the vertical line of the "H" is a tube containing a solution of the compound, and the other vertical line of the "H" is a tube containing a solvent which the compound is not soluble in, and the horizontal line of the "H" is a tube which joins the two vertical tubes, which also has a fine glass sinter that restricts the mixing of the two solvents.
→
Solvent added (clear) to compound (orange) to give a compound solution
(orange) → 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
solvent interface (green) over time
- Once single perfect crystals have been obtained, it is recommended that the crystals are kept in a sealed vessel with some of the liquid of crystallisation to prevent the crystal from 'drying out'. Single perfect crystals may contain solvent of crystallisation in the crystal lattice. Loss of this internal solvent from the crystals can result in the crystal lattice breaking down, and the crystals turning to powder.
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.
