Supporting Information for
Visualizing molecular chirality in the organic chemistry laboratory using cholesteric liquid
crystals
Maia Popova, Stacey Lowery Bretz, and C. Scott Hartley*
Department of Chemistry and Biochemistry, Miami University, Oxford, Ohio 45056
E-mail: scott.hartley@miamioh.edu
Student Lab Manual ...................................................................................................................... S2
Instructor’s Notes .......................................................................................................................... S8
Characterization .......................................................................................................................... S16
S1
Student Lab Manual
Objectives





To investigate chirality by observing its macroscopic manifestations
To synthesize an imine
To determine the absolute stereochemistry of a product mixture
To examine liquid crystals and their phase behavior
To identify a structure-property relationship between chiral dopants and liquid crystals
The Assignment


Complete Part 1 individually. Complete Part 2 in groups of three. All notebook entries
and answers to questions should be prepared individually.
Turn in the notebook pages for this experiment with answers to questions as a summary
report.
Safety





1-phenylethylamine is corrosive.
The toxicity of the synthesized chiral imine is unknown. Many imines are carcinogenic.
Biphenyl-4-carboxaldehyde, ethanol, MBBA, and EBBA are irritants to the skin, eyes,
and respiratory system.
Wear gloves during all operations involving the chiral dopant.
The synthesis should be conducted in a fume hood.
Introduction
Substances can change from one state of matter to another. For example, water can exist as a
solid (ice), liquid, or gas (water vapor). Some substances can exist in states in addition to these
conventional ones.1 For example, N-(4-methoxybenzylidene)-4-butylaniline (MBBA) is a
crystalline solid below 21 °C. When heated above 21 °C (its melting temperature), it turns into a
cloudy fluid. When the cloudy fluid is further heated to 45 °C (its clearing temperature), it
becomes a clear liquid (Fig. 1). Thus, an additional intermediate state exits between the
crystalline solid state and the isotropic liquid state, called a liquid crystal (LC) state.2
Figure 1. Transition temperatures of liquid crystal N-(4-methoxybenzylidene)-4butylaniline (MBBA).
As suggested by the name, liquid crystals combine some properties of conventional liquids
with those of crystals. Molecules in the liquid state are randomly oriented, whereas molecules in
crystalline phases are arranged in a lattice with orientational order. Liquid crystals can be defined
S2
as “ordered fluids” because their molecules have some elements of orientational and/or
positional order. Hence, they exhibit some properties characteristic of the crystalline state, but
the molecules are free to diffuse and flow (Fig. 2).2
Figure 2. Transitions between solid, liquid crystalline, and liquid states of matter.
Figure 3. Cholesteric liquid crystal obtained by addition of a chiral molecule to an achiral
nematic host; p is the pitch of the helix.
Chart 1. The chiral dopant N-(4-phenylbenzylidene)-1-phenylethanamine will be mixed with the
mixture of two nematic liquid crystals N-(4-methoxybenzylidene)-4-butylaniline (MBBA) and 4(ethoxybenzylidene)-4-butylanline (EBBA).
Cholesteric LCs can be obtained by dissolving a chiral compound, the “dopant”, in an achiral
nematic LC host. Addition of the chiral dopant induces the helical structure of the chiral nematic
liquid crystalline phase, defined by its pitch p, where p is the length of the helical axis over a full
360° rotation of the rod-like molecules.3 As helices are inherently chiral, the configuration of the
constituent molecules is manifested in the structure of the bulk phase. The two enantiomers of a
chiral compound give helices that twist in opposite directions (i.e., left- or right-handed helices).
The compounds to be used in this experiment are given in Chart 1.
A useful property of cholesteric phases is the selective reflection of polarized light (not the
same as the optical rotation of linearly polarized light taught in lecture). Incident light with a
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wavelength similar to the pitch (p) of the helix is reflected when it strikes a film of a cholesteric
liquid crystal. The observed color therefore depends on the pitch of the helix. The reflected light
has another important property: it is circularly polarized, with the polarization dependent on the
twist sense of the cholesteric helix. The material reflects only circular polarized light with the
same handedness as the handedness of the helix. The opposite handedness is transmitted through
the material. In other words, a left-handed helix will selectively reflect left-handed circularly
polarized light.3 This combination of properties has found broad application in the production of
liquid crystal thermometers.4 This method can also be used for enantiomeric excess (ee)
determination by visual color inspection. The method makes use of the sensitivity of the pitch
towards the strength of the chiral perturbation. A chiral analyte of interest is doped into the liquid
crystal, and, based on its enantiomeric excess, a whole spectrum of different colors can be
obtained, allowing the ee to be rapidly estimated.5
Figure 4. Selective reflection of the circularly polarized light
Chirality plays a very important role in the pharmaceutical industry. For example, amino
acids are the building blocks of proteins and enzymes in our body. All standard amino acids,
except glycine, are chiral. Therefore, the chemistry of our bodies is controlled by chiral
molecules. This plays a very important role in drug design and development as proteins are often
selective towards one stereoisomer. Although one enantiomer of the drug may be therapeutic, the
other can cause irreparable harm.6 The drug thalidomide is a perfect example of how chirality
impacts differing selectivity. It was designed as a treatment for morning sickness for pregnant
women (Chart 2). Although enantiomerically pure (R)-thalidomide possesses a sedative effect
and helps calm down the nervousness of pregnant women who ingest it, (S)-thalidomide causes a
specific birth defect known as phocomelia (deformed limbs).7 Presently, the government closely
monitors chirality in drug development to minimize side effects.
Chart 2. (R)-Thalidomide (left) and (S)-thalidomide (right)
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In the experiment that follows, you will observe the interaction between chiral dopants and
nematic liquid crystalline hosts as indicated by light reflection. The absolute stereochemistry of
the dopant will be also determined.
Part 1: Synthesis of the Chiral Dopant
Chart 3. Starting materials to synthesize the chiral dopant: (R)-1-phenylethylamine (left), (S)-1phenylethylamine (center), biphenyl-4-carboxaldehyde (right)
Reflux
Obtain 0.26 mL of an amine of unknown configuration from the teaching assistant. Weigh
0.25 g of biphenyl-4-carboxaldehyde in a weigh boat. Measure 6.0 mL of 95% ethanol. Transfer
the materials into a 50 mL round-bottom flask that will serve as a reflux flask; make sure to
perform a quantitative transfer of the amine by rinsing the vial with ethanol. Add a stir bar to the
reflux flask. Heat at reflux for 15 minutes once the mixture starts boiling.
While reaction mixture is boiling, measure about 7.0 mL of 95% ethanol into a graduated
cylinder. Place the graduated cylinder in a beaker filled with ice.
Also while the reaction mixture is boiling, determine the melting and clearing temperatures
of liquid crystal EBBA.
After refluxing, disconnect the heating supply and allow the solution to cool. Place the room
temperature flask in a beaker filled with ice.
Vacuum filtration
Collect the crystals from the reaction mixture by vacuum filtration through a Büchner funnel.
Wash the crystals with small amounts (no more than 7 mL total) of ice-cold ethanol. Leave the
crystals on the Büchner funnel to dry. When the crystals are fully dried, collect them into a
previously tared weigh boat and determine the mass of the sample.
Characterization
Obtain a melting point and the IR spectrum of the synthesized chiral dopant.
Part 2: Mixing LCs with Dopant
Prepare a 13% by mass mixture of synthesized chiral dopant and liquid crystals MBBA and
EBBA as follows: in order to keep the liquid crystals in 1:1 ratio to each other, weigh 0.10 ± 0.01
g of EBBA and measure 0.10 ± 0.01 mL of MBBA. Weigh 0.030 ± 0.003 g of synthesized chiral
dopant. Vigorously grind these substances in a mortar with a pestle for about 2 minutes until you
get a slightly opalescent mixture. Let it sit for 2 more minutes. Place a drop of the LC-chiral
dopant mixture on a glass slide. Cover with a cover slip.
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Characterization
For this part of experiment, students will work in groups of three. Each group of students will
share one pair of 3D glasses.
Using the LC/chiral dopant mixture prepared earlier, shear the cover slip on your and your
partners’ mixtures. Observe what happens while shearing the cover slip for each member of the
group, alternating between different lenses of the 3D glasses. Record your observations. Slightly
heat your glass slides. Once mixtures on the glass slides are no longer in the liquid crystal phase,
shear the cover slip. Observe what happens while shearing cover slips again alternating between
different lenses of the 3D glasses. Record your observations. Let your glass slides cool down to
room temperature. Observe your glass slides with and without shearing of the cover slips,
alternating between different lenses of the 3D glasses. Record your observations.
Obtain two glass slides from the teaching assistant, one with known (R)-dopant in the
mixture and one with the (S)-dopant. Shear the glass slides in the same way as you did for the
glass slides with your LC/dopant mixtures and with the racemic mixture. Record your
observations for each lens of the 3D glasses. Calibrate the lenses of the 3D glasses. Determine
which enantiomer you were assigned.
Make a 13% racemic dopant – liquid crystals mixture. Place a drop of this mixture on a glass
slide. Cover with a cover slip. Shear, heat, and cool down the glass slide in the same way as you
did for the glass slides with your LC/chiral dopant mixtures.
The Report
Answer each of the following questions in your notebook.
1.
2.
3.
4.
5.
6.
Write the reaction mechanism for the dopant synthesis.
Calculate the percent yield of the chiral dopant.
Interpret the IR spectrum of the synthesized chiral dopant.
Report the melting point of the synthesized dopant.
At what temperatures is EBBA a crystalline solid? A liquid crystal? A liquid?
3D glasses use circularly polarized filters in their lenses. Which lens of the 3D glasses was
used to identify which enantiomer of the dopant? How can you explain your observations?
7. Which enantiomer of 1-phenylethylamine were you assigned? Explain your answer.
8. What did you notice once the glass slide had been heated? What did you observe once the
slide had cooled down to room temperature? Explain your observations.
9. Explain your observations of the racemic mixture using the glasses.
10. Draw the R and S enantiomers of the amine used for the synthesis, show the chirality
center and rank group priorities to demonstrate the configuration of each enantiomer.
11. List some properties that you would expect the enantiomers prepared by your group to
share. What properties are not shared by the enantiomers?
References
1. Chemical of the week – Liquid Crystals.
http://scifun.chem.wisc.edu/chemweek/liqxtal/liqxtal.html (accessed March 16, 2015).
2. Verbit, L. Liquid Crystals – Synthesis and Properties. J. Chem. Educ. 1972, 49 (1), 36-39.
S6
3. Mulder, D. J.; Schenning, A. P. H. J.; Bastiaansen, C. W. M. Chiral-nematic liquid crystals as
one dimensional photonic materials in optical sensors. J. Mater. Chem. C, 2014, 2, 66956705.
4. Li, Y.; Wang, M.; Urbas, A.; Li, Q. A photoswitchable and thermally stable axially chiral
dithienylperfluorocyclopentene dopant with high helical twisting power. J. Mater. Chem. C,
2013, 1, 3917-3923.
5. van Delden, R. A.; Feringa, B. L. Colour indicator for enantiomeric excess and assignment of
the configuration of the major enantiomer of an amino acid ester. Chem. Commun. 2002,
174-175.
6. Brooks, W. H.; Guida, W. C.; Daniel, K. G. The significance of chirality in drug design and
development. Curr. Top. Med. Chem. 2011, 11 (7), 760-770.
7. Eriksson, T.; Bjorkman, S.; Hoglund, P. Clinical pharmacology of thalidomide. Eur. J. Clin.
Pharmacol. 2001, 57, 365-376.
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Instructor’s Notes
Pre-Lab
In order for students to calibrate the lenses of the 3D glasses, prepare (R)- and (S)-mixtures
for the “known” glass slides by following the same procedure as given in the part 1 of the
Student Lab Manual. It might be more convenient to double the amount of the reactant to obtain
a bigger amount of the chiral dopant N-(4-phenylbenzylidene)-1-phenylethanamine. For each
prepared glass slide, one or two drops of the chiral dopant – LCs mixture is needed.
In order to avoid pre-lab preparation of the chiral dopant, students can be told which lens of
3D glasses is responsible for which enantiomer: the (R)-chiral dopant – LCs mixture is seen
through the right lens of the 3D glasses (right circular polarizer in a standard pair of glasses) and
the (S)-chiral dopant – LCs mixture is observable through the left lens of the 3D glasses (left
circular polarizer). Note that 3D glasses produced by another manufacturer might differ from the
ones used by our students.
Reflux
Students perform synthesis individually. For the characterization in part 2, students will work
in groups of three.
Prepare and label vials with 0.26 of (R)- and (S)-1-phenylethylamine that will be given to
students in the beginning of lab as the reactant of unknown configuration.
In order to achieve a decent purity of the final product, it is very important for the students to
measure the right amount of biphenyl-4-carboxaldehide.
Mixing LCs with dopant
In order to achieve color generation, students need to grind the mixture of N-(4methoxybenzylidene)-4-butylaniline (MBBA) and 4-(ethoxybenzylidene)-4-butylanline (EBBA)
liquid crystals with the synthesized chiral dopant very vigorously for not less than 2 minutes
(Fig. 1). Before placing a drop of the mixture on a glass slide, students should let it sit for 2 more
minutes.
*
N
N
O
MBBA
N
O
EBBA
Chiral dopant
Figure 1. Mixing nematic liquid crystals N-(4-methoxybenzylidene)-4-butylaniline (MBBA) and
4-(ethoxybenzylidene)-4-butylanline (EBBA) with the chiral dopant of unknown configuration.
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Characterization
For this part of the experiment, students will work in groups of three. We suggest to make
groups of three instead of groups of two in order to make it more difficult for students to guess
which amine configuration they were assigned. This will also make it more difficult for students
to find out the stereochemistry of their chiral dopants by process of elimination. Two types of
groups of three can be formed:
Type 1
Type 2
Two students that made (R)-chiral
dopant – LCs mixture
Two student that prepared
prepared (S)-chiral dopant –LCs
mixture
One student that prepared prepared (S)chiral dopant –LCs mixture
One students that made (R)-chiral dopant –
LCs mixture
When shearing the glass cover slips on the glass slide before heating, students should observe
multicolored shimmering or sparkling of their mixtures. Shearing promotes a planar alignment of
the molecules with the long molecular axis being oriented in the plane of the glass slide (Fig. 2).
Depending on the configuration of the chiral dopant used, the students will be able to see the
color generation in the (R)-chiral dopant – LC mixtures through the right lens of the 3D glasses
(right circular polarizer) and through the left lens of the 3D glasses for the (S)-chiral dopant – LC
mixtures. TAs should guide students through their observations. An easy way to switch between
the lenses of the 3D glasses is to simply cover one of the lenses with palm and then switch and
cover the other lens with a palm.
Figure 2. Observation of the nematic LCs – chiral dopant mixture without 3D glasses at room
temperature under shearing. On the left mixture before touching, on the right the same mixture
during shearing.
While heating the glass slides, the mixtures will melt (transition from LC state of matter to
isotropic liquid) and will look transparent. Shearing will not promote any color generation. After
cooling and shearing, in some cases, students will obtain permanent color of their mixtures
without subsequent shearing. The mixtures obtained might vary in color from red-orange to
green (Fig. 3). Students might also see a combination of colors. This may be a result of small
variations in the concentration of the LCs-chiral dopant mixtures or because planar alignment of
molecules was only partially achieved (Fig. 4).
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(S)-Mixture
left
Without
polarizers
(R)-Mixture
right
left
Under circular
polarizers
Without
polarizers
right
Under circular
polarizers
Figure 3. Observation of the students’ nematic LCs – chiral dopant mixtures with and without
right and left circular polarizers after heating and cooling.
In order to calibrate the lenses of the 3D glasses, students will make similar observations of
the glass slides with mixtures of known stereochemistry. Label the corresponding glass slides
either R or S (Fig. 4).
Figure 4. Observation of the students’ nematic LCs – (S)-chiral dopant mixture through different
lenses of 3D glasses.
In order to prepare a 13% by mass racemic mixture of synthesized dopant and liquid crystals
MBBA and EBBA, the students need to figure out which dopant enantiomer each member of the
group has. Groups have to grind in the mortar 0.015 ± 0.003 g of synthesized (R)-chiral dopant,
0.015 ± 0.003 g (S)-chiral dopant, 0.10 ± 0.01 g of EBBA, and 0.10 ± 0.01 mL of MBBA. When
observing the glass slide alternating between different lenses of 3D glasses while shearing the
cover slip, students will not observe any color generation. The color is sufficiently sensitive to
enantiomeric excess that the students should not observe it even if they are not all that close to a
perfect 1:1 mixture.
Incorporation of the Lab in the Teaching Curriculum
The laboratory activity can be combined with polarimetry and resolution of racemic 1phenylethylamine by crystallization with tartaric acid experiments. The chiral dopant has a 1.4°
specific rotation value.
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Required Materials
Name
1. (R)-(+)-1-Phenylethylamine
CAS
388669-9
2. (S)-(-)-1-Phenylethylamine 262786-3
3. 4-Biphenylcarboxaldehyde 321836-8
4. N-(4-Methoxybenzylidene)- 262274-butylaniline
73-6
5. 4’-Ethoxybenzylidene-429743butylaniline
08-6
6. Ethanol 95%
64-17-5
Amount
per
Student
0.26 mL
Available
from
Catalog
Number
70674
0.1 mL
AK
Scientific
AK
Scientific
AK
Scientific
VWR
0.1 g
VWR
0.26 mL
0.25 g
Price
$50 for 100
mL
65632
$50 for 100
mL
69735
$150 for
100 g
TCM0275- 25 g for
025G
$71.35
TCE0262- 25 g for
025G
$69.37
13 mL
The 3D glasses were purchased from Amazon.com as a 4 pack for $19.95 (B00GTVV3NM).
One can also purchase a set of left/right circular polarizers from Polarization.com for $20 for a
pair of 21×21 cm2 films that can be cut (PFC-EC Economy Circular Polarizer Pair (left and right
hand)).
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Answers to Student Lab Report Questions
1. Write the reaction mechanism for the dopant synthesis.
2. Calculate the percent yield of the chiral dopant.
Assuming that actual yield is 0.324 g:
𝑔
1-phenylethylamine’s mass: 0.26 𝑚𝐿 ∗ 0.94 𝑚𝐿 = 0.244 𝑔
Reagent
1-phenylethylamine
biphenyl-4-carboxaldehyde
Molar Weight (g/mol)
121.18
182.22
N-(4-phenylbenzylidene)-1phenylethanamine
285.39
Mass (g)
0.244
0.249
Moles
2.01 × 10−3
1.37 × 10−3
(limiting
reagent)
𝑔
Theoretical yield: 1.37 × 10−3 𝑚𝑜𝑙 ∗ 285.39 𝑚𝑜𝑙 = 0.391 𝑔
0.324 𝑔
% yield:
0.391 𝑔
∗ 100 % = 82.9 %
3. Interpret the IR spectrum of the synthesized chiral dopant.
Type of bond
C=C
C–H
C=N
Wavenumber (cm-1)
~ 3050
~ 2970
~ 1645
4. Report the melting point of the synthesized dopant.
88–90 °C
5. At what temperatures is EBBA a crystalline solid? A liquid crystal? A liquid?
Crystalline solid: under 36 °C.
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Liquid crystal: 36–78 °C.
Liquid: above 78 °C.
6. 3D glasses use circularly polarized filters in their lenses. Which lens of the 3D glasses was
used to identify which enantiomer of the dopant? How can you explain your observations?
The (R)-enantiomer and (S)-enantiomer show colors through different lenses of the 3D glasses.
When shearing the sample mixtures, color is observed through the right lens when looking at the
(R)-dopant – LCs mixture and through the left lens for the (S)-dopant – LCs mixture. The light
reflected by the (R)-mixture has the same handedness as the right circular filter in the 3D glasses.
The color is transmitted only through this lens. The light reflected by the (S)-mixture has the
same handedness as the left circular filter in the 3D glasses. The color is transmitted only
through the left lens.
7. Which enantiomer of 1-phenylethylamine were you assigned? Explain your answer.
R if the color is observed through the right lens of 3D glasses.
S if the color is observed through the left lens of 3D glasses.
8. What did you notice once the glass slide had been heated? What did you observe once the
slide had cooled down to room temperature? Explain your observations.
When heating the glass slide, the colored cholesteric liquid crystal mixture transforms into a
transparent, colorless isotropic liquid. The color disappears because the structure is no longer
helical and does not possess the property of selective reflection of light.
Once the glass slide cools down, the mixture again reaches the cholesteric liquid crystalline state
of matter. A cholesteric twist is regenerated and the material again selectively reflects circularly
polarized light.
9. Explain your observations of the racemic mixture using the glasses.
When mixing equal amounts of R- and S-chiral dopants with non-chiral MBBA and EBBA liquid
crystals, the mixtures remain white in color because no chiral twist is generated in the structure
of nematic liquid crystals.
10. Draw the R- and S-enantiomers of the amine used for the synthesis, show the chirality center
and rank group priorities to demonstrate the configuration of each enantiomer.
11. List some properties that you would expect the enantiomers prepared by your group to share.
What properties are not shared by the enantiomers?
Share: physical properties.
Do not share: interaction with polarized light as well as interaction with other chiral compounds.
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Grading Rubric
1. Write the reaction mechanism for the dopant synthesis.
Correct
Some incorrect mechanism steps, or wrong arrow directions, or missing
charges
All wrong
2 pts.
1 pt.
0 pts.
2. Calculate the percent yield of the chiral dopant.
Correct (not grading on students’ % yield values, only correctness of
calculations)
All wrong
1 pt.
0 pts.
3. Interpret the IR spectrum of the synthesized chiral dopant.
C=N, C-H, C=C
C-H, C=C, not including C=N OR only C=N peak
One out of three not including C=N
2 pts.
1 pt.
0 pts.
4. Report the melting point of the synthesized dopant.
In range of 79-95 oC
Differ significantly from the range
1 pt.
0 pts.
5. At what temperatures EBBA is solid? Liquid crystal? Liquid?
Solid below 29 oC, liquid crystal between 29-80 oC, liquid above 80 oC
Differ significantly from the range
1 pt.
0 pts.
6. 3D glasses use circularly polarized filters in their lenses. Which lens of the 3D glasses was
used to identify which enantiomer of the dopant? How can you explain your observations?
Right lens – R, left lens – S. Explanation based on the specific reflection
of circularly polarized light
Correct observations with lenses but wrong explanation
Both wrong
3 pts.
2 pts.
0 pts.
7. Which enantiomer of 1-phenylethylamine you were assigned? Explain your answer.
Correct enantiomer (check with the unknown key) and correct explanation 2 pts.
Correct enantiomer, but wrong explanation
1 pt.
All wrong
0 pts.
8. What did you notice once the glass slide had been heated? What did you observe once the
slide cooled down to room temperature? Explain your observations.
All correct
Partial credit:
Answer for the first question
Answer for the second question
3 pts.
1 pt.
1 pt.
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Explanation
All wrong
1 pt.
0 pts.
9. Explain your observations of the racemic mixture using the glasses.
Correct observation AND explanation (LC is no longer helical)
Correct observations, but incomplete reasoning (interaction of two
enantiomers with the polarized light), or wrong explanation
All wrong
2 pts.
1 pt.
0 pts.
10. Draw the R- and S-enantiomers of the amine used for synthesis, show the chirality center and
rank group priorities to demonstrate the configuration of each enantiomer.
Both structures correct
One or both wrong
1 pt.
0 pts.
11. List some properties that you would expect the enantiomers prepared by your group to share.
What properties are not shared by the enantiomers?
Both correct
Share: physical properties
Not share: interaction with polarized light AND interaction with other
chiral compounds
One correct
Both wrong
Total number of points: 20
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2 pts.
1 pt.
0 pts.
Characterization
The values for the melting range obtained by students vary from 64 to 90 °C. However, some
students obtain well over 100%, typically because they did not allow sufficient time for the solid
product to dry.
When analyzing the IR spectra, students are expected to note the absence of the carbonyl
peak and presence of imine peak at ~1645 cm-1.
Nuclear magnetic resonance spectrum of the chiral dopant N-(4-phenylbenzylidene)-1phenylethanamine
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Representative student infrared spectrum of the chiral dopant N-(4-phenylbenzylidene)-1phenylethanamine:
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