INTRODUCTION

Solid compounds synthesized in the

Organic laboratory usually need to be
purified before final confirmation tests
are performed
One of the most commonly used
techniques is to purify a sample by
dissolving it in a suitable solvent and
recrystallizing the pure compound from
the saturated solution by slow cooling

INTRODUCTION

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The most common method of purifying

solid organic compounds is by
recrystallization. In this technique, an
impure solid compound is dissolved in a
solvent and then allowed to slowly
crystallize out as the solution cools. As
the compound crystallizes from the
solution, the molecules of the other
compounds dissolved in solution are
excluded from the growing crystal lattice,
giving a pure solid.
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Purpose of process

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Mainly for the purification of solid

crystalline compounds.
Melting point is one of the ways of
determining the purity of the compound.

PRINCIPLES OF
RECRYSTALLLIZATION

Based on difference between the solubilities of the

pure substance and impurities in the solvent or
mixture of solvents
2 different situations could arise
Either the impurities have greater solubility in the
solvent than the pure substance being recrystallized
In which case the impurities will be retained in the
mother liquor and several recrystallizations will
yield the pure substance
Or the impurities will have less solubility in the
solvent than the substance being recrystallized in
which case the impurities will not dissolve and more
crystals will be obtained

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PRINCIPLES OF
RECYSTALLIZATION

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At normal laboratory temperatures the

substance being recrystallized is not
soluble. However ,increasing the
temperature results in increased
solubility of the pure substance
At/near the boiling point of the solvent,
maximum solubility is obtained.

Solubility of salicylic acid in

water

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PRINCIPLES OF
RECRYSTALLIZATION

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After reaching the boiling point, reduction

of temperature results in precipitation of
crystal nuclei
Presence of crystal nuclei promotes
crystal growth which continues until the
temperature is stabilized at the normal
laboratory temperature

PRINCIPLES OF
RECRYSTALLIZATION

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Assumptions made are:

The impurities are present in
comparatively small quantities i.e. less
than 5%.
The effect of either component (i.e. the
impurity and the pure substance) on the
solubility of the other is neglected.

PROCEDURE

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There are different types of

recrystallzation techniques, namely
Single-solvent recrystallization
Multi-solvent recrystallization
Hot filtration-recrystallization

MATERIALS/APPARATUS

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Fluted filter paper

Conical flask
Bunsen burner
Appropriate solvents
Funnel
Suction filter
Test materials
Measuring cylinder

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Procedure(cont.)

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Summary of Single-solvent
Recrystallization Steps
Add a small quantity of appropriate
solvent to an impure solid.
Apply heat to dissolve the solid.
Cool the solution to crystallize the
product.
Use vacuum filtration to isolate and dry
the purified solid.
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Addition of solvent

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Choose a solvent such that the impure

compound has poor solubility at low
temperatures, yet is completely soluble at
higher temperatures. The point is to fully
dissolve the impure substance when it is
heated, yet have it crash out of solution
upon cooling. Add as small a quantity as
possible to fully dissolve the sample. It's
better to add too little solvent than too
much. More solvent can be added during
the heating process, if necessary.
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Heating the suspension

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After the solvent has been added to the

impure solid, heat the suspension to fully
dissolve the sample. Usually a hot water
bath or steam bath is used, since these
are gentle, controlled heat sources. A hot
plate or gas burner is used in some
situations

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Cooling the solution

Once the sample is dissolved, the solution is cooled to force

crystallization of the desired compound.
Slower cooling may lead to a higher purity product, so it's
common practice to allow the solution to cool to room
temperature before setting the flask in an ice bath or refrigerator.
Crystals usually begin forming on the bottom of the flask. It's
possible to aid crystallization by scratching the flask with a glass
rod at the air-solvent junction (assuming you are willing to
purposely scratch your glassware). The scratch increases the
glass surface area, providing a roughened surface on which the
solid can crystallize. Another technique is to 'seed' the solution by
adding a small crystal of the desired pure solid to the cooled
solution. Be sure the solution is cool, or else the crystal could
dissolve. If no crystals fall out of solution, it's possible too much
solvent was used. Allow some of the solvent to evaporate. If
crystals do not spontaneously form, reheat/cool the solution.

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FILTER AND DRY THE PRODUCT

Crystals of purified solid are isolated by

filtration. This is usually done with vacuum
filtration, sometimes washing the purified solid
with chilled solvent. If you wash the product, be
sure the solvent is cold, or else you run the risk
of dissolving some of the sample.
The product may now be dried. Aspiring the
product via vacuum filtration should remove
much of the solvent. Open-air drying may be
used as well. In some cases, the
recrystallization may be repeated to further
purify the sample.

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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.
However the impure solution can be
concentrated and the procedure repeated
to gather a "second crop" of crystals.

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MELTING POINT DETERMINATION

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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
higher melting points and melt over a
narrower temperature range. Obviously
other analytical techniques can be used
to assess compound purity such as NMR
spectroscopy and elemental analysis.
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PRECAUTIONS

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The mixture is warmed slowly to facilitate

the crystallization process.
The solution is allowed to cool naturally
to room temperature to aid the formation
of fine crystals.
The filter paper should adhere over the
perforated plate the suction filter.
The filter paper must be moistened
before filtration with the chosen solvent.
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PRECAUTIONS(cont)

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Suction filtration should be done gently.

Excess addition of solvent should be
avoided.
When two solvents A and B are used for a
Multi-solvent recrystallization process,
solvents A and B must be miscible.

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CHOICE OF SOLVENT

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Substance should be insoluble in solvent

at room temperature but soluble at
elevated temperatures.
Impurities should be either soluble or
completely insoluble in solvent.
Should yield well defined crystals of
required compound.
Should possess low boiling point.

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CHOICE OF SOLVENT(cont)

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It should not react with the compound of

interests.
Should have similar chemical properties
as the compound to be recrystallized.
Other factors to be considered include
ease of manipulation, flammability and
cost.

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MODERN ADVANCEMENTS
It has been proven that under conditions of
microgravity better protein crystals can be
obtained. This is due to the fact that under
these conditions, movement induced by
concentration gradient is almost eliminated.
Furthermore, a recent development has been
the use of a Craig tube in ultra micro scale
recrystallization

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Craig tube
Craig tubes are
particularly useful for
recrystallizing amounts
of solid less than ~100
mg, the main advantage
being that it minimizes
the number of transfers
of solid material and
thus maximizes the yield
of crystals. The
separation of the
crystals from the mother
liquor with the Craig
tube is very efficient,
and little time is required
for drying the crystals.
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X-RAY DIFFRACTOMETER

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NMR SPECTROMETER
HWB-NMRv900

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APPLICATION OF
RECRYSTALLIZATION
Generally, recrystallization in pharmacy
is used for purification of pharmaceutical
formulations .

Chemicals and reagents used for

pharmaceutical processes must be
achieved in their unadulterated states
as much as possible. And this can be
acquired by many techniques such as
filtration, fractional distillation as well as
the normal distillation.
Sometimes these processes may not be
enough for the purification of several
preparations and therefore the
recrystallization process is employed.

Chemicals and reagents used for

pharmaceutical processes must be
achieved in their unadulterated states
as much as possible. And this can be
acquired by many techniques such as
filtration, fractional distillation as well as
the normal distillation.
Sometimes these processes may not be
enough for the purification of several
preparations and therefore the
recrystallization process is employed.

Method for purifying adipic

acid by recrystallization

Adipic acid is one of the two base

materials for preparing Nylon 6-6. For the
applications of Nylon 6-6 it is necessary
to have a very high purity, and this purity
must exist already at the stage of the
precursors, especially at the adipic acid
stage.

The direct oxidation of cyclohexane to

adipic acid is generally carried out in the
presence of cobalt. The adipic acid
obtained contains traces of cobalt
catalyst.

The present invention consists in an improved

process for crystallization or recrystallization
of adipic acid, characterized in that the said
crystallization or recrystallization is carried
out in at least one carboxylic acid having a
melting point of less than 20 C.
The carboxylic acids employed in the present
process are, more particularly, aliphatic
carboxylic acids which are saturated or which
contain an ethylenic unsaturation.

Acetic acid and pentenoic acids are

preferred, acetic acid owing to its
availability and to its use in the synthesis
of adipic acid from cyclohexane, and
pentenoic acids because they are an
intermediate in the preparation of adipic
acid from butadiene.
The purity of the adipic acid recrystallized
in this way may be improved further when
recrystallization is carried out in the
presence of carbon monoxide.

The carbon monoxide can make up at least part of

the atmosphere above the solution in the
crystallization or recrystallization reactor (or
reactor headspace) or can create within the said
reactor a pressure which is greater than the
atmospheric pressure.
In practice, the process will therefore be operated
under an absolute pressure of from 0 bar
(preferably at least 0.5 bar) to 50 bars of carbon
monoxide, the upper limit not being critical in
nature but being representative of industrial
apparatus which is not excessively expensive.

The crude adipic acid subjected to recrystallization

according to the present process is usually an
adipic acid which has already undergone one or
more purification treatments, in particular by
crystallization from water, by refining or else by
distillation, to give it a minimum purity of
approximately 95%.
Generally, the adipic acid recrystallized by the
process of the invention has a purity of from 95 to
99.95%.

The recrystallization consists in taking the

adipic acid to be purified and dissolving it in the
minimum amount of hot aliphatic carboxylic
acid, i.e. usually at a temperature from 80 to
250 C., optionally under an at least partial
pressure or atmosphere of carbon monoxide,
and then inducing crystallization of the
dissolved adipic acid by cooling the solution,
optionally after having seeded the solution
using crystals of
pure adipic acid.

THE END.

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