Recrystallization (chemistry)

Chemistry
In chemistry, recrystallization[1] 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),
which includes recrystallization. There are also different recrystallization techniques that can
be used such as:
[edit] Single-solvent recrystallization
Typically, the mixture of "compound A" and "impurity B" are dissolved in the smallest
amount of solvent to fully dissolve the mixture, thus making a saturated solution. Normally
the solvent is warmed before use, increasing solubility. 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 formed.

→ 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 non-saturated solution
(pale-orange).

Crystallization of Ibuprofen in HCl(aq)

The crystallization process requires an initiation step. Once a small crystal has formed, more
crystals can grow from that crystal. Since "Compound A" is in excess this will usually result
in these crystals forming first and thus leaves a greater ratio of impurity in solution. Thus the
resulting solid is more pure than the original mixture.
The level of purity can then be checked by taking a melting point range of the solid and
comparing it to an accepted melting point range, if one exists. Compounds that are more pure
have less melting point depression and melt over a narrower temperature range. Naturally,
other analytical techniques can also be used to assess compound purity, including NMR
spectroscopy and elemental analysis.
This purification technique results in the inevitable loss of the part of "compound A" that
remains in solution. A yield of 80% would be considered quite good.[citation needed] However, the
impure solution can be concentrated and the procedure repeated to gather a "second crop" of
crystals.
Successful recrystallization depends on finding the right solvent. This is usually a
combination of prediction/experience and trial/error. The mixture must be soluble at higher
temperatures, and must be insoluble (or have low solubility) at lower temperatures.
[edit] 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
non-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 non-saturated second mixed solvent system (green-blue)

[edit] Hot filtration-recrystallization

Hot filtration[2] 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 needs to ensure that the filtration apparatus is hot to stop the dissolved
compounds crystallizing from solution during the filtration step thus forming crystals on the
filter paper or funnel.
One way of achieving 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 non-saturated
solution (pale-orange)

Another info:

It is possible to purify compounds by recrystallizing them in a solvent in which they are

soluble at a
high temperature but insoluble at a low temperature. The target compound dissolves in the
solvent at
high temperatures allowing the researcher to filter out insoluble impurities. At low
temperature the
target compound forms crystals and precipitates out of solution while the soluble impurities
remain
dissolved.
Impure crystalline (solid) substances can be purified by recrystallization from a suitable
solvent. This
process depends on the observations that:
1) most compounds are more soluble in hot solvents than in cold ones and
2) impurities (such as sand and dirt) are likely to have solubilities different than the desired
compound.
The technique by which a solid compound is purified by its characteristic solubilities is called
recrystallization. Recrystallization involves:
a) dissolving the impure material in a minimum amount of boiling solvent,
b) filtering the hot solution to remove any insoluble impurities,
c) allowing the solution to cool and to deposit crystals of the compound,
d) filtering the crystals from the solution that may contain dissolved impurities and
e) drying the crystals.
If recrystallization is to be effective, the solvent must be properly selected.
A good recrystallization solvent should:
1) dissolve a moderate quantity of the target substance near its boiling point but only a small
quantity near 0 °C,
2) not react with the target substance
3) dissolve impurities readily at low temperatures or not dissolve them at any temperature and
4) be readily removed from the purified product.