11/30/2012
Recrystallization of Acetanilide
Double, double toil and trouble;
Fire burn and cauldron bubble.
Cool it with a baboon's blood,
Then the charm is firm and good.
Insulin crystals
Methods for Separation and
Purification
Recrystallization
Extraction
Distillation
Chromatography
1
11/30/2012
Recrystallization
Recrystallization is generally limited to
purification of compounds which are solids
at room temperature.
Recrystallization takes advantage of the fact
that most crystal growth prefers
incorporation of molecules of the same
structure – leaving other structures
(impurities) out of the crystals.
Recrystallization Steps
1) Dissolve the impure mixture in the
minimum amount of hot solvent. The
solvent needs to be one in which the
desired compound has low solubility
at room temperature.
2) Cool the mixture slowly to allow the
product to form crystals as it comes
out of solution.
2
11/30/2012
Recrystallization
3) Isolate the purified crystals by
separation from the solvent containing
the impurities (generally by a process
called filtration)
4) Dry the purified solid – removal of the
traces of solvent by evaporation at
room temperature or, more forcibly,
by applying a vacuum to the crystals.
Advantages of Recrystallization
Low Cost
High Purity possible
Small scale to large scale in
industrial settings
3
11/30/2012
Disadvantages
Loss of some amount of the
desired compound
Determining a suitable solvent
may be difficult
Some mixtures may not separate
well
Unsuitable for liquids
Acetanilide
O
acetanilide
N
H
CH3
O
NH2
HO
CH3
In today’s experiment, you will do a
recrystallization of an impure mixture of
acetanilide.
4
11/30/2012
Solvent Selection
The first step in recrystallization
requires selecting a suitable solvent.
– High solubility near boiling pt. of
solvent; low solubility at 0o – 25o
– Impurities: either high solubility or
no solubility is ideal
– Solvent bp lower than compound’s
mp is advantageous
Acetanalide
The electron pairs on oxygen and nitrogen
be the site of hyrogen bonds from a solvent.
The hydrogen on the electronegative N can
hydrogen bond to electron pairs of apolar
solvents.
5
11/30/2012
Why Purification?
Two factors are involved – one is
differential solubility – the other is the
nature of crystal formation.
Crystallization can be a very selective
process. Each crystal is a highly
ordered assembly of molecules.
Why Purification? Selectivity of
Crystal Formation
Once a crystal starts
to form, the next
molecule which bestfits to the surface of
the crystal lattice is
the molecule of the
same compound, not
impurity molecules.
6
11/30/2012
Why Purification? Solubility Curve
▼
20
solute
concentration
(mg/mL)
saturated solution
+ solid
10
0
unsaturated solution
(all compound in solution)
Z
temperature
X
Solubility increases as temperature increases
Steep curve more efficient
Solubility
Curve
Here’s what
happens as a
saturated
solution cools.
7
11/30/2012
Solubility of Impurity
20
solute
concentration
(mg/mL)
saturated solution
+ solid
10
0
unsaturated solution
(all compound in solution)
Z
temperature
X
Purification occurs if impurity is significantly
more soluble, or it is present in small amount.
Oil Formation
Sometimes as the solution cools, the
compound comes out of solution as an
oil – a liquid, rather than as crystals.
This will always occur if the saturation
temperature is above the melting pt.
Although the oil might solidify upon
further cooling, the solid will contain
impurities in it.
8
11/30/2012
Correcting Oil Formation
Once an oil forms, it must be
redissolved and steps taken to induce
the compound to form crystals.
First, redissolve the oil by heating and
adding a small additional amount of
solvent.
You should make sure the solution is
then cooled slowly.
Prevent Oil Formation
As the solution
cools, use a stirring
rod to make small
scratches inside the
flask below the
liquid line – this
provides a fresh
surface that may
induce crystal
growth.
9
11/30/2012
Prevent Oil Formation
If crystals of the compound are
available, dropping one into the
solution just at the temperature
before oiling begins may initiate
crystallization
See p. 39 of lab manual for
advanced techniques
Procedure
The acetanilide mixture you will be
using contains two impurities – one of
which is totally insoluble in water.
This will have to be removed by the
technique of ‘hot filtration’. You will
need to dissolve all the acetanilide in
hot water and then filter to remove the
insoluble solid.
10
11/30/2012
Procedure
The resulting filtrate will need to be
reheated and cooled slowly to crystallize
pure acetanilide. Rapid cooling and
crystallization leads to small crystals
with large total surface area that absorbs
impurities and leads to trapping of
impurities in the crystal lattice as
crystals form.
Speed of Crystal Growth
SLOW crystal growth
FAST crystal growth
11
11/30/2012
Procedure
After the solution has cooled to room
temperature, you will cool it in an icebath to maximize crystal formation,
and then isolate the crystals by a
second filtration.
Procedure - Equipment
Reread the instructions on hot vacuum filtration
and on isolation of crystals (pp. 33 – 38) before
starting.
You will need an Erlenmeyer flask, a filter flask,
and a Buchner funnel from your bin.
Attach
clamp
here
12
11/30/2012
Procedure – Vacuum Filtration
Remove some rings from
the steam bath to lower the
water beaker into the bath;
Use a clamp to hold your
beaker.
To help prevent
crystallization during the
hot filtration, you will need
to warm the Buchner funnel
on the steam bath.
Procedure – Vacuum Filtration
Make sure you clamp the filter flask before
placing the Buchner funnel on top or
attaching the vacuum hose.
Set up this filtration apparatus in front of
the mini-hood, not off to the side.
13
11/30/2012
Procedure – Vacuum Filtration
The isolated crystals are rinsed
(washed) with a small amount of cold
solvent to remove the solvent
containing the impurities from the
surface of the crystals.
Do NOT turn off the water aspirator
without first removing the hose from
the filter flask.
Procedure – Characterization of
Product
To obtain an accurate yield and melting
point, the crystalline product must be free of
water. In this case, we will allow the
crystals to ‘air-dry’ until next lab period.
Wrap your crystals on the filter paper with a
piece of 15-cm filter paper to form a
‘packet’. Tape it closed and label with name
section #, date, and compound name.
Store the sample in your TA’s section
drawer until next week.
14
11/30/2012
Procedure – Characterization of
Product
Next week you will obtain a weight and
melting point for your product.
Clean-up
The filtrate solution should be poured
into the proper waste container in the
hood.
Rinse the used glassware with acetone,
collecting and disposing of the first
rinse into the waste container in the
hood. Final rinses go into the acetone
wash container in the sink.
15
11/30/2012
Clean-up
Next week, your product and filter
papers go into the waste container and
your melting point capillaries go into
the box designated for broken glass.
Safety
Acetanilide can be an irritant. Wash your
hands immediately following any contact.
Be careful with HOT water.
Use clamps to secure flasks
Thanks to:
http://www.chem.ualberta.ca/~orglabs/index.html
http://www.chemhelper.com/recryst.html
16