Download Recrystallization: A Purification Technique

A Purification Technique
By: Elizabeth N. Timblin
Chem 203 Section 002
October 26, 2013
TA: Ajay Sathe
Professor: Dr. Jacqueline Bortiatynski
TABLE OF CONTENTS
Introduction ......................................................................................................................................3
Experimental Procedure ...................................................................................................................6
Results and Discussion ....................................................................................................................8
Conclusion .....................................................................................................................................10
References ......................................................................................................................................11
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INTRODUCTION
Recrystallization is a simple, convenient, and inexpensive technique used to
remove small impurities from solid compounds. This technique exploits the property of
compounds that, when temperature increases, solubility increases. The higher the temperature of
the solvent, the more material can be dissolved. Slow cooling separates the saturated solute in the
form of crystals and leaves the impurities in the solution. The desired solute’s crystalline
structure will be different than that of the impurities and will therefore not fit together when
recrystallizing. So as the solute begins to form crystals, the impurities will be excluded from the
forming lattice structure. The result is the pure compound while the impurities are filtered off.
Recrystallization is not recommended for removing large amounts of impurities so it can
be used in conjunction with extraction to isolate as much product as possible. Thin-layer
chromatography (TLC) can also be used to monitor the synthesis of a compound to show small
amounts of impurities.
Recrystallization is important when creating pure compounds suitable for pharmaceutical
purposes. The Federal Drug Administration (FDA) has standards for the purity of compounds
used in making medicines. Recrystallization is a valuable process used to meet these standards.
The purpose of the experiment outlined in Lab Guide for Chemistry 203 was to
synthesize acetanilide, determine a suitable recrystallization solvent, and purify the acetanilide
using recrystallization.
To synthesize acetanilide, aniline was mixed with acetic anhydride and allowed to react
for 30 minutes. Vacuum filtration was used to isolate the acetanilide solid from the acetic acid.
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Fig 1: Synthesis reaction
H3C
O
O
C
C
NH2
NH
+
O
CH3
C
CH3
O
+
O
acetic anhydride
aniline
C
HO
acetanilide
CH3
acetic acid
The reaction mechanism is a three step process. The first step is a nucleophilic addition
where aniline is the nucleophile and the lone pair of electrons on the nitrogen bonds with a
carbon on the acetic anhydride molecule. The second step is a nucleophilic elimination of an
acetate ion by breaking the bond between the carbon and the oxygen that was central to acetic
anhydride. The third step is a proton transfer. The products are acetanilide and acetic acid. A
diagram of the mechanism is below.
Fig 2: Step 1 of Reaction Mechanism – Nucleophilic Addition
H
H
H
N
+
O
O
C
C
H3C
aniline
O
+
H
CH3
N
O-
C
O
CH3
C
acetic anhydride
O
H3C
Fig 3: Step 2 of Reaction Mechanism – Nucleophilic Elimination
H
+
H
N
CH3
C
O
H
O-
+
H
N
O-
CH3
C
O
+
C
O
CH3
4
C
O
acetate
H3C
Fig 4: Step 3 of Reaction Mechanism – Proton Transfer
H
+
H
N
O-
CH3
C
O
+
C
H
O
HO
N
CH3
CH3
C
acetate
O
+
C
O
CH3
acetic acid
acetanilide
Possibly the most important part of the recrystallization process is determining an
effective solvent. When choosing a solvent, there are four properties to be considered.
1. One property is the solubility at different temperatures. The desired solvent will not
easily dissolve the solute at room temperature but will completely dissolve the solute
at higher temperatures. To help determine solubility of a solute with a solvent, the
like-dissolves-like principle can be used, i.e. a solvent with a polarity similar to that
of the solute.
2. To keep the impurities from crystallizing with the desired solute, they need to be very
soluble at room temperature or insoluble at high temperature. The impurities that are
insoluble at high temperatures can be filtered out and the impurities highly soluble at
room temperature will remain in the solvent as it is cooled and the desired solute
crystallizes.
3. No reaction should occur between the solvent and the solid that is to be purified. If a
reaction occurs, a new compound is formed.
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4. For quicker drying, the solvent should be easily evaporated. A lower boiling point
would be desired.
A suitable solvent was used to recrystallize the remaining acetanilide. The purified
crystals were vacuum filtered from the solvent. Melting point, NMR and IR data were all
obtained using the purified crystals.
Acetanilide has been used as one of many chemicals to produce photographic images. It
is widely used in pharmaceuticals. It is used in the synthesis of penicillin, to prevent the
breakdown of hydrogen peroxide, and as a painkiller such as acetaminophen because of its
analgesic properties.
EXPERIMENTAL PROCEDURE
Synthesis of Acetanilide
Two mL of aniline and 3 mL of acetic anhydride were placed in a 50 mL flask with 15
mL of distilled water. The mixture was set to stir for approximately 30 minutes. Using a 125 mL
filter flask and the porcelain Büchner funnel, the acetanilide was isolated via vacuum filtration.
The product was washed with 1 to 2 mL ice water and then allowed to dry on the filter paper for
approximately 20 minutes. Prior to recrystallization, the weight of product was determined to be
3.5108 g. This weight was used to calculate the % yield of crude acetanilide.
Fig 5: Calculation of % Yield of Crude Product
Theoretical
volume of
density of
yield
= limiting x limiting x
reagent
reagent
molecular
ratio of
weight of x reagent to
reagent
product
molecular
x weight of
product
= 2 mL aniline x 1.0217g aniline x 1 mol aniline x 1 mole x 1.3517g acetanilide =2.966g acetanilide
mL aniline
93.13g aniline
1 mole
1 mole acetanilide
% Yield = actual yield/theoretical yield x 100% = 3.5108g/2.966g x 100% = 118.4%
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Finding a Suitable Recrystallization Solvent
Using a sand bath with a heating mantle, four solvents were tested for solubility. In each
of four reaction tubes, 50 mg of product was added to 0.5 mL of the different solvents. These
solvents included water, ethanol, dichloromethane, and hexanes. Solvents that dissolved the solid
easily at room temperature were eliminated as a suitable solvent for recrystallization. Ethanol
dissolved the acetanilide immediately and the dichloromethane dissolved the product with a
slight stirring of the mixture. Both were eliminated not realizing that if less solvent or more
product were used, the dichloromethane wouldn’t have dissolved the product as easily. The
remaining solvents were heated to boiling for about one minute. To prevent bumping of the
solvent when boiling, wooden boiling sticks were added to the reaction tubes. The solvent that
completely dissolved the solid at the high temperature was selected as the recrystallization
solvent. Ethanol would not dissolve the product even after adding a little more solvent. This left
water as the most suitable recrystallization solvent.
Purification of Acetanilide by Recrystallization
The weight of the dried crude product after testing solvents was obtained and then a
melting point was acquired. Testing solvents and completely drying the product had reduced the
weight to 1.9503g. The melting point of the crude acetanilide ranged from 108°C to 112°C.
A minimal amount of solvent needed to be used in order to easily saturate the solvent.
About 20 mL of the chosen solvent, water, was used for each gram of product. The product and
the solvent were heated in a beaker using a hot plate. Additional solvent was heated in a second
beaker in case more was needed to dissolve the product. While heating, the mixture was stirred
and a small amount of additional solvent was added to help remove some solid product from the
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side of the beaker. Once all of the product was dissolved, the beaker was removed from the heat
and allowed to slowly cool to room temperature. The beaker was then placed on ice for about 10
minutes. The crystals were once again vacuum filtrated with the porcelain Büchner funnel. The
purified acetanilide crystals were allowed to finish drying until the following lab. Once the
product was dry, weight of purified acetanilide was determined to be 1.6111g and melting point
ranged from 116°C to 118°C.
Fig 6: Calculation of % Yield of Pure Product
% Yield = actual yield/theoretical yield x 100% = 1.6111g/2.966g x 100% = 54.32%
The purified acetanilide was prepared for NMR and IR analysis. Approximately 40 mg of
product was diluted with d-chloroform and used for NMR analysis. Approximately 20 mg of the
purified acetanilide crystals were used for IR analysis.
The NMR spectra indicated hydrogens from a methyl group near 2 ppm, hydrogens from
an aromatic group between 7 and 7.5 ppm, and hydrogens from an amine group at about 7.9
ppm. The IR spectra indicated a C=O bond at about 1660 cm-1 and an N-H bond at about 3292
cm-1.
Finally, % recovery from the crude product to the purified product was calculated.
Fig 7: % Recovery Calculations
% Recovery = mass of crude product x 100% = 1.6111g x 100% = 82.608%
mass of purified product
1.9503g
RESULTS AND DISCUSSION
When weighing the initial crude product after synthesizing acetanilide, the mass was
greater than the theoretical yield based on the volume of aniline used in synthesis. This error was
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due to the water that remained in the product. A more accurate mass could have been obtained if
the product had been properly dried.
Four solvents including water, ethanol, dichloromethane, and hexanes were used with a
small amount of crude product to test solubility at room temperature and higher temperatures.
Ethanol readily dissolved all of the product and dichloromethane dissolved the product with
slight stirring. These two solvents were eliminated although dichloromethane could have been
used if there were a higher product to solvent ratio. When heated, the product dissolved in the
water and reformed crystals with cooling. However, when the product was heated in hexanes, the
product did not fully dissolve; therefore, the hexanes were also eliminated.
A mass of the product was obtained after synthesizing the acetanilide and then again after
some of the product had been used to obtain a melting point and test solvents. The % yield of the
purified acetanilide reflects this loss of product.
The melting point of the crude acetanilide ranged from 108°C to 112°C. The expected
melting point range was 113°C to 116°C. Because impurities prevent the acetanilide from
forming a perfect crystal lattice, the bond strength is reduced and less energy is needed to break
them. Therefore, an impure compound will have a lower melting point than a pure compound.
The melting point range of the pure acetanilide was 116°C to 118°C. Being that the pure
substance will have a cleaner crystal lattice and stronger bonds, more energy is required to break
those bonds. The higher melting point reflects that of a more pure compound.
The NMR spectrum that was obtained appeared to show no impurities. There was a peak
representing the 3 hydrogens of the methyl group present only in the acetanilide at approximately
2.1 ppm, a broad shallow peak for the 1 hydrogen from the amino group rather than 2 hydrogens
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that are present in aniline around 7.9 ppm, and an aromatic cluster of peaks for 5 hydrogens
between 7.0 and 7.6 ppm. This clearly indicates that acetanilide is present in the sample and
aniline is not.
The IR spectrum showed a peak representing the aromatic C=O at approximately 1660
cm-1. The reactant aniline does not have this functional group therefore indicating that acetanilide
was indeed synthesized. Also, a primary amine group such as that in aniline would show two
peaks on the IR spectrum between 3290 and 3500 cm-1. While the peak present on the IR
spectrum does seem closer to the wavelength associated with the primary amine group of aniline
rather than of the secondary amine group of the acetanilide, there is only one peak present,
therefore confirming again that the product is purified acetanilide.
CONCLUSION
Based on the improvement of the melting point from the crude acetanilide to the purified
acetanilide, the presence of the methyl group on the NMR spectra, and the presence of the C=O
peak and single peak of the amino group, it has been determined that acetanilide was synthesized
and purified using recrystallization.
Perhaps more product may have been obtained if dichloromethane had been used as the
recrystallization solvent. Not only would it have evaporated quicker, it may have produced a
better product yield. In order to improve yield in the future, not only could a more suitable
solvent be used but more product could be obtained from glassware. Minimizing transfer from
one piece of glassware to another and washing each piece as much as possible would help
prevent product loss.
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REFERENCES
Bortiatynski, Jackie. Lab Guide for Chemistry 203. Hayden McNeil Publishing: Plymouth, 2014;
p 143-165.
Baumann, Jacob B. Solvent Selection for Recrystallization: An Undergraduate Organic
Experiment. J. Chem Educ. [Online] 1979, 56, 64.
http://pubs.acs.org/doi/abs/10.1021/ed056p64?prevSearch=purification%2Brecrystallization%2B
acetanilide&searchHistoryKey= (accessed November 13, 2013).
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