Practical I: Resolution of 1-Phenylethylamine
Reference: Adapted from Ault, A. J. Chem. Educ. 1965, 42, 269.
Readings: Organic Chemistry by David Klein, Chapter 5
Summary
In this experiment (S)-(–)-1-phenylethylamine will be isolated. Racemic (1)phenylethylamine will be reacted with enantiomerically pure (2R,3R)-(+)-tartaric acid to
form diastereoisomeric salts which can be resolved by selective crystallization from
methanol. The isolated salt will be converted to the optically active free base by
treatment with sodium hydroxide. A polarimeter will be used to determine the optical
rotation of the product, from which we can determine enantiomeric excess and evaluate
the efficiency of our resolution.
Introduction
An object that has a non-superimposable mirror image is referred to as being chiral
(from the Greek chiros meaning handed). Examples of such objects include many
organic and inorganic molecules, of which many occur naturally. These two nonsuperimposible stereoisomers are referred to as enantiomers. An equimolar mixture of
two enantiomers is known as a racemic mixture (or racemate). Enantiomers have
identical physical properties (e.g. melting point, boiling point, and solubility in methanol).
However, the isolation of a single enantiomer from a racemic mixture can sometimes be
accomplished by a process known as chiral resolution.
Mirror plane
Me H
H Me
NH2
H2N
O
OH
OH
HO
OH O
(R)-(+)-1-phenylethylamine
(S)-(-)-1-phenylethylamine
(2R,3R)-(+)-tartaric acid
Non-superimposable
Object - image 
ENANTIOMERS
(R)-1-Phenylethylamine (depicted above) cannot be superimposed with its mirror image.
When a racemic mixture (a 1:1 ratio of enantiomers) of 1-phenylethylamine is reacted
with a single enantiomer of tartaric acid,1 two diastereomeric salts form (in a 1:1 ratio).
These complexes are not mirror images of one another since only a single enantiomer
of tartaric acid is used in the reaction. Thus, (R)-amine, (R, R)-tartaric acid salt and (S)amine, (R, R)-tartaric acid salt are formed.
Tartaric acid occurs naturally and is widely available as it is a byproduct in the wine
making industry. 1
RACEMATE
(1:1 mixture)
Me H
O
H Me
NH2
+
H2N
OH
OH
HO
OH O
(S)-(-)-1-phenylethylamine
(R)-(+)-1-phenylethylamine
(2R,3R)-(+)-tartaric acid
MeOH
DIASTEREOMERIC SALTS
O
Me H
NH3
OH
H Me
OH
O
O
H3N
OH
OH
O
OH O
OH O
(S)-1-phenylethylamine (2R,3R)-tartrate
(R)-1-phenylethylammonium (2R,3R)-tartrate
Less soluble (crystallizes from solution)
More soluble (stays in solution)
However, unlike enantiomers, diastereomers (generally) have different physical
properties, so we would expect that the above complexes should have different
solubilities in methanol. In fact these two diastereomeric complexes have a significant
solubility difference in methanol. The (R)-amine:(R, R)-tartaric acid salt is more soluble
in methanol than the (S)-amine:(R, R)-tartaric acid salt. This difference permits the
isolation of one of the diastereomeric salts by selectively crystallizing out the (S)-amine,
(R, R)-tartaric acid salt from a methanolic solution. Once the solid (S)-amine, (R, R)tartaric acid complex is isolated, treatment with excess aqueous sodium hydroxide will
convert the salt to the free amine (organic soluble) and disodium tartrate (aqueous
soluble). Drawing on your acid/base extraction skills, you soon will have a sample of 1phenylethylamine that should predominantly consist of (S)-(–)-1-phenylethylamine. Now
let’s discuss how to analyze the enantiomeric composition of your sample.
H Me
H3N
O
OH
H Me
OH
O
NaOH
Na
H2N
OH O
(S)-1-phenylethylamine (2R,3R)-tartrate
O
OH
O
O
OH O
(S) (-)-1-phenylethylamine
(Dichloromethane soluble)
Na
(2R,3R)-tartrate
Enantiomers do not interact with plane-polarized light in the same way, a
phenomenon that chemists have made good use of. Recall that light is a wave that
consists of oscillating electric and magnetic fields. A regular beam of light has electric
(and magnetic) fields that oscillate in all directions perpendicular to the direction of
beam travel. A beam of light with an electric field oscillating in only a single plane is
called plane-polarized light, or more simply polarized light. When regular light is passed
through a polarizer (imagine this as functioning like a slit) only light that oscillates
parallel to this slit can pass through it and as a result the light that emerges from the
polarizer only oscillates in one direction.
When plane-polarized light is passed through a single enantiomer of a chiral molecule
(more commonly a solution of a single enantiomer of a chiral molecule), the plane of
polarization is rotated. When the opposite enantiomer is used, the plane of polarization
is rotated in an equal and opposite direction. Samples that rotate polarized light are said
to be optically active. The magnitude of this rotation, , is reported in degrees by a
device called a polarimeter. A schematic of a polarimeter is shown below. If the light
has been rotated in a clockwise direction, the  is assigned a positive (+) value; if the
light has been rotated in a counterclockwise direction, the is assigned a negative (–)
value.

For a given enantiomer the degree of rotation is dependent on the concentration of
the compound (c), the path length of the sample cell (l), and the wavelength of light that
is used. Typically, the yellow light of a sodium lamp (the “D” line of Na, wavelength =
589 nm) is used as a light source. If you have ever spilled salt on a gas burner the
flame will burn yellow – this is due to emission at 589 nm. The equation below can be
used to calculate the specific rotation, sample, which is a constant for a single
enantiomer of a chiral compound in a given solvent at a given temperature and
wavelength. For neat samples, the concentration (c) is taken to be the density of the
compound.
.
= Specific rotation
 = observed rotation
c = concentration (g/mL)
l = pathlength (dm (1 dm = 10 cm))
D = sodium D-line (589 nm)
t = temperature of sample
It is usually reported in the following format:
#.## (c #.#, solvent)
A racemic mixture will not rotate polarized light and is said to be optically inactive.
Achiral molecules also do not rotate plane-polarized light. Any excess of one
enantiomer over the other will result in the rotation of polarized light, with the maximum
rotation occurring when the sample consists of a single enantiomer. The enantiomeric
excess (ee) of a compound can be calculated using the equation below. The ee of a
racemic mixture is 0% while the ee of a single enantiomer is 100%. ee = % of the major
enantiomer - % of the minor enantiomer. By comparing the specific rotation of a sample
prepared in the laboratory with the published specific rotation of an enantiomerically
pure sample, one can calculate the optical purity of the sample. If the relationship
between concentration and rotation is linear, then optical purity = %ee.
Optical purity
. 100%

Procedure
Place 7.8 g of (L)-(+)-tartaric acid and 125 mL of methanol in a 250 mL Erlenmeyer
flask. Heat this mixture on a hot plate until the solution is nearly boiling. Slowly add
6.25 g of racemic α-methylbenzylamine to this hot solution. Allow the contents to cool,
and then cover the top of the flask with aluminum foil and let stand overnight. The
crystals that form should be prismatic. If needles form, they will not be optically pure
enough to give a sufficient resolution of isomers -- they must be prisms! Needles
should be redissolved (by careful heating) and cooled to slowly crystallize again (if this
is necessary, your TA will take care of this between periods). When you recrystallize in
this fashion you can seed the reaction with a prismatic seed. If you have a mixture of
prisms and needles, you can heat until most of the solid is dissolved. Usually the
needles will dissolve faster than the prisms in this case. (If you get the incorrect
crystals, your TA will check during the week and redissolve/seed as necessary).
Continue from here during next lab period
Once you have obtained the correct type of crystals, you should isolate them by vacuum
filtration. The crystals can be washed with a small portion (~ 5 mL) of cold methanol.
Partially dissolve the crystalline salt in 25 mL of water and treat with 4 mL of 50%
NaOH. The resultant solution is extracted with 3 x 10 mL of dichloromethane. The
organic layers are combined in a stoppered flask and dried with 1 gram of anhydrous
sodium sulfate for about 10 minutes. Decant the dichloromethane into a preweighed
100 mL round bottom flask and by simple distillation (use a steam bath). Avoid
transferring any of the white solid. Calculate the percent yield of the resolved amine
based upon the amount of racemate you started with. Prior to determining the optical
rotation, allow the TA to examine your sample and to check the mass of the material
obtained. Obtain the optical rotation by dissolving your sample in MeOH (use 1.00 g in
10 mL). If you have less than 1 g, use what you have, but you must record the mass
accurately – your TA will provide details on how to use the polarimeter.
Literature Data
(S)-(–)-1-phenylethylamine:

D = –30, c = 0.1 g/mL in EtOH; density = 0.952 g/mL
Cleanup
• The sodium hydroxide solution should be disposed of in the Basic Aqueous Waste.
• MgSO4, filter paper, and excess tartaric acid should be put in the Solid Waste.
• The phenylethylamine, methanol, and ether go in the Non-halogenated Organic
Waste.