Survey of Organic Chemistry Laboratory Manual

Crystallization
Solid organic compounds prepared in the laboratory or extracted from natural sources,
such as leaves, are often impure. One of the steps usually involved in the purification of
such solid compounds is crystallization. It is the slow formation of a crystalline solid. In
general, the crude compound is first dissolved in a minimal amount of hot solvent. At this
stage, insoluble impurities can be separated from the hot solution by gravity filtration. If
colored impurities are present, the solution is treated with decolorizing charcoal and then
filtered. The hot, saturated solution is then allowed to cool slowly so that the desired
compound crystallizes. When the crystals are fully formed, these are isolated from the
mother liquor (the solution) by filtration.

The success of this process is based on the difference in the solubilities of the compound
and the impurities, and on the fact that most compounds are more soluble in a hot solvent
than in a cold one.

Crystallization is different from precipitation since the latter is a rapid formation of solid
material. If the hot, saturated solution is cooled too quickly, the compound may precipitate
instead of crystallizing. The precipitate may still contain impurities. However, if the solution
is allowed to slowly cool down, impurities are likely to be excluded. The molecules in the
crystal structure are in equilibrium with the molecules still in solution. Molecules unsuitable
for the crystal lattice tend to return to the solution. Thus, crystallization is a more selective
process. Since impurities are often found in low concentrations, they tend to remain in
solution as cooling continues.

To obtain really pure compounds, recrystallization of the harvested crystals is often

employed. But this is with the disadvantage of possible losses of the desired compound,
which remains in the solution.

Solvents for Crystallization

The ideal solvent for the crystallization of a particular compound is one that:

1. does not react with the compound;

2. boils at a temperature below the compound’s melting point;
3. dissolves a moderately large amount of compound when hot;
4. dissolves only a small amount of compound when cool;
5. is moderately volatile so that crystals can be readily dried;
6. is nontoxic, nonflammable, and inexpensive.

As with all ideal things, such an ideal solvent does not exist. However, the main
consideration for choosing a solvent is this: that the compound should be moderately
soluble in it. Crystallization brings us back to the rule of thumb: like dissolves like. Polar
compounds are soluble in polar solvents. So how do we make sure that our target
compound is just moderately soluble in a given solvent? Through experiment. Fortunately
for us, information about good solvents or solvent systems for the crystallization of certain
compounds can be found in literature.

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Mixed Solvent Technique

Sometimes, it is hard to find a solvent that best fits the solubility criteria for a particular
compound. In such case, a mixed solvent or solvent pair may be used. Table 1 lists the
common solvent mixtures. Initially, the crude compound is dissolved in a minimum amount
of the boiling solvent in which it is soluble. Following this, a second hot solvent, which is
miscible with the first and in which the solute is relatively insoluble, is added dropwise to
the boiling mixture until the mixture becomes cloudy. Cloudiness indicates precipitation.
When extensive cloudiness occurs, more of the first solvent should be added to clear the
cloudy solution. At this point, the solution is saturated, and as it is cooled, crystals should
separate. It is important not to add an excess of the second solvent or to cool the solution
too rapidly. Doing so will only cause the solute to oil out or separate as a viscous liquid. If
this happens, the solution should be reheated and added with more of the first solvent to
dissolve the oil.

Table 1. Common solvent mixtures.

Methanol-Water Ether-Acetone
Ethanol-Water Ether-petroleum Ether
Acetic acid-Water Benzene-Ligroin
Methylene Chloride-
Acetone-Water
Methanol
Ether-Methanol Dioxane-Water

Safety Using Solvents

Most organic solvents are either flammable or toxic, or even both. And since crystallization
involves heating these solvents, care must be taken. For example, if a solvent is very
flammable or is low-boiling, the safest heat source would be a hot plate. Heating must also
be done under a hood. Bunsen burners or any direct flame may only be used in solvents that
are not too flammable.

Toxic solvents must not be sniffed, and should be handled under a hood.

Boiling chips should be used when heating solvents to reduce the risk of uneven boiling,
which may result in bumping or splattering of hot liquid. These chips release bubbles when
hot, ensuring even heating. Fresh boiling chips must be used at all times.

Different Crystallization Techniques

Ways to crystallize a compound include the following:

1. Heating the solution then cooling it down gradually;

2. Dissolving the product then letting the solvent evaporate at room temperature;
3. Dissolving sample then cooling it in the refrigerator/cooling refrigerator (a special
refrigerator that cools down very slowly);
4. Allowing a “non-solvent” to diffuse into the solution of interest thereby changing
the solubility of the solute in the new solvent system (refer to Figure 1); and

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Figure 1. Non-solvent diffusing into the solution

5. Simply placing the system in a cold room since some materials are best crystallized
at low temperatures.

Steps in Crystallization
Dissolving the Compound
The solid compound will be dissolved in a minimum amount of hot solvent in an Erlenmeyer
flask. A flask is preferred over a beaker since it minimizes the possibility of splattering
liquids. It can also be corked and stored.

Solid lumps must be pulverized first before dissolving in the solvent. To make sure that only
a minimum amount of solvent is used, small portions of the solvent are added until the
compound completely dissolves. Usually, excess solvent can be reduced by boiling it off.
There will be no need for gravity filtration if the resulting solution looks clean and clear.
Colored impurities can be eliminated by adding decolorizing charcoal.

Using Decolorizing Charcoal

Decolorizing charcoal is added in the crystallization process when the solution appears to
be contaminated with these colored substances. The fine particles of carbon have a large
surface area per gram that can adsorb organic compounds, especially those that are
colored and polymeric. The charcoal contains multiple bonds and a number of hetero-
atoms like oxygen being present in the form of hydroxyl groups, making it possible to
adsorb the impurities.

Only a small amount of decolorizing charcoal is to be added to the solution. Since the
carbon particles adsorb organic compounds, it might as well adsorb some of the desired
compound. As much as possible, it must be made certain that a maximum amount of the
compound is recovered from the sample. To prevent a large amount of sample loss,
addition of an excess solvent always accompanies every decolorizing process.

The decolorizing step is generally performed after the crude compound has been dissolved
in an appropriate solvent system. When adding decolorizing charcoal to a solution, it is very
important that an excess amount of fresh, cold solvent is added first into the solution or the
solution is allowed to cool down. The carbon particles can act as minute boiling chips. If
they are added to a hot solution, frothing may occur. It is also because of this that the
mixture will froth once it is heated with decolorizing charcoal.

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After gently boiling the solution, it is then subjected to gravity filtration. The receiving flask
and funnel must be very warm to avoid premature formation of crystals. The addition of
more solvent prior to boiling also prevents premature crystallization during gravity
filtration. If the filtrate still appears to have some color, the solution may be treated again
with decolorizing charcoal and refiltered. Once the solution appears colorless and clear,
excess solvent may then be boiled off as before.

Filtering Insoluble Impurities

Gravity filtration is used to filter insoluble impurities (refer to section in Filtration). In the
case of filtering solid impurities, it must be ensured that premature crystallization or
precipitation does not occur in the process. Thus, the glassware immediately in contact
with the hot solution must also be kept hot.

The glassware (an Erlenmeyer flask and a funnel) must be preheated in an oven, and used
while very hot at the time when the solution to be filtered is ready. The receiving flask will
also serve as the site for crystallization later on. Keep the solution being filtered hot. While
waiting for some of the solution poured on the funnel to drain into the receiving flask, heat the
remainder of the unfiltered solution to keep it hot.

If premature crystallization occurs in the funnel, wash the crystals down with fresh, hot
solvent. It would be better to add only small portions of the hot crystallization solution
instead of filling the funnel to the brim and keep the rest of the solution hot. After filtering
all of the solution, wash the empty flask with a small amount of fresh, hot solvent to
dissolve remaining traces of crystals in the flask and then pour this into the filter paper.

If crystals immediately form in the receiving flask, it can be reheated to redissolve the
crystals. If the crystals remain undissolved, additional hot solvent can be added to dissolve
these formations. At this point, excess solvent may then be boiled off.

Crystallizing the Compound

The crystallization flask must be covered with a watch glass during cooling down to prevent
dust contamination and solvent evaporation. The flask must be set aside in a place where it
cannot be disturbed. Bumping the flask may induce precipitation instead of crystallization.
Placing the hot flask in an ice-bath also produces precipitates rather than crystals. Thus, it is
important to take note that crystallization is a slow cooling process rather than a fast and
rapid one. It is important to ensure that there is no abrupt change in temperature;
otherwise, the impurities may be trapped inside the crystal lattice making the isolated
crystals smaller and impure, as shown in Figure 2.

Figure 2. Diagrams showing the fate of a solution that is

cooled down quickly; the triangle represents the impurities
trapped inside the crystals formed by the hexagon.

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On the other hand, if the solution is cooled slowly, as shown in figure 3, the impurities
trapped inside the crystal lattice of hexagons may be displaced by particles which fit better
in the crystal lattice, which are the hexagons as well. This results to a large and pure
crystallized product. It is important that the solution be cooled gradually but not too slowly
that impurities adhere in the crystal matrix again.

Figure 3. Diagrams showing the fate of a solution that is

cooled down slowly

If several days are required for crystallization, the solution must first be cooled to room
temperature before corking the flask and storing it. Rubber stoppers are not to be used
when organic solvents are involved to prevent the former from being dissolved.

Problems Encountered during Crystallization:

Case 1: No crystallization occurs
It may be that the solution was supersaturated. Scratching the sides of the flask will
produce microcrystals of glass which may serve as templates for crystallization. A seed
crystal may also be used as a template. Your instructor may have a few crystals previously
prepared. Seed crystals can also be obtained from the tip of your stirring rod as the solvent
evaporates. Note that this stirring rod was previously immersed in the solution where
crystals are to grow.

It may also be that too much of the solvent was used, especially if scratching or adding a
seed crystal did not work. In this case, boiling off excess solvent may be employed.

Case 2: Oiling out

Sometimes, when the melting point of the compound is lower than the boiling point of the
solvent, the compound separates as an oily substance instead of crystallizing. This may also
be the case if impurities present in the compound depress its melting point. Reheating the
mixture to dissolve the oil is encouraged. Additional hot solvent may be added, boiling off
excess when necessary.

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If oiling out still occurs, let this oil solidify. The solidified oil may then be separated and
redissolved in fresh, hot solvent. By this time, much of the impurities may have been
removed to allow crystallization to proceed more smoothly.

Isolating the Crystals

At this point, the crystallization solution would have already cooled to room temperature,
and stayed at that temperature for quite some time. Placing the flask in an ice-bath may
also increase crystal yield. The crystals may be separated from the mother liquor through
suction filtration (refer to section on Filtration).

Optional: The mother liquor collected from suction filtration may still contain some
dissolved compound and provide another batch of crystals, aptly called the second crop.
The crystals may be obtained by boiling off excess solvent, and allowing the solution to cool
down as before. Each successive crop, though, will be less pure than the previous one. Thus,
only one to two crops are usually taken. All harvested crystals can be purified further by
recrystallization in fresh solvent.

References
Department of Chemistry and Biochemistry, University of Colorado at Boulder; 2014 May
14 [cited 2014 June 19]. Available from: http://orgchem.colorado.edu/Technique/
Procedures/Crystallization/Crystallization.html.

Department of Chemistry, Stony Brook University; 2001 February 1 [cited 2005 May 22].
Available from: http://www.sinc.sunysb.edu/Class/orgolab/hotfiltration.PDF.

Fessenden RJ, Fessenden JS. Techniques and Experiments for Organic Chemistry. USA:
Merck & Co.; 1983.

Most CF. Experimental Organic Chemistry. USA: Wiley & Sons; 1988.