SEM 6 Gas ChromatographyMass Spectrometric Analysis of Derivatives of Dibenzalacetone Aldol Products

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Gas Chromatography−Mass Spectrometric Analysis of Derivatives of
Dibenzalacetone Aldol Products
Hailey N. Lynch, Austin H. Harnage, and Anuradha Liyana Pathiranage*
Cite This: https://doi.org/10.1021/acs.jchemed.1c00595 Read Online
ACCESS Metrics & More Article Recommendations *sı Supporting Information
ABSTRACT: The aldol condensation reaction is one of the many
synthesis reactions carried out in second semester organic
chemistry laboratories. This reaction was integrated into a novel
experiment requiring students to synthesize dibenzalacetone
derivatives using the crossed-aldol condensation by reacting
different types of benzaldehyde derivatives with acetone, followed
by analyzing those products using spectrometric and spectroscopic
methods, especially gas chromatography−mass spectrometry
(GC−MS). The main objective of this 2 week lab experiment
compared to other procedures in the literature was the analysis of
the final aldol product using GC−MS methods rather than solely
nuclear magnetic resonance (NMR) spectroscopic methods.
During the first week’s 3 h laboratory period, students completed
the reaction with a known benzaldehyde derivative and acetone to synthesize their aldol product. In the second week, students
calculated the percent yield of their product, determined the product’s melting point range, and analyzed the product by thin-layer
chromatography, NMR, and GC−MS methods. Students also strengthened their skills of spectral interpretation using NMR
spectroscopy, especially distortionless enhancement by polarization transfer NMR, an NMR technique rarely covered in
undergraduate organic laboratory sections. Students spent more classroom time during week two, analyzing GC−MS data. Students
were shown how to use molecular model kits to understand the fragmentation of compounds in the mass spectrum. As a result, the
students who performed this experiment increased their general knowledge of GC−MS spectrometric techniques, including
identification of compounds based on their fragmentation pattern.
KEYWORDS: Upper-Division Undergraduate, Organic Chemistry, Hands-On Learning/Manipulatives, Synthesis, Gas Chromatography,
Mass Spectrometry, NMR spectroscopy, Laboratory Instruction
■ INTRODUCTION
The aldol reaction is an organic chemistry reaction that is
taught in lecture and often carried out in the organic chemistry
laboratory.1−4 Most organic chemistry laboratory manuals
include an aldol condensation reaction.5,6 Students typically
start with a known or unknown aldehyde, such as
benzaldehyde, and a known or unknown ketone and combine
the two reactants to produce a yellow-hued aldol product,
which is then analyzed using melting point and nuclear
magnetic resonance (NMR) methods. In this undergraduate
lab, students carried out an aldol synthesis with different types
of benzaldehyde derivatives and one simple ketone, acetone.
All students worked with acetone but were given different
benzaldehyde derivatives, and the reactants were combined in
the presence of sodium hydroxide as the base catalyst (Scheme
1).
The aldol condensation reaction is a simple C−C coupling
reaction that yields a distinct bright-yellow precipitate when
successfully performed, making it ideal for undergraduate-level
organic chemistry laboratories. Aldol condensation reactions
typically yield products in a 1:1 molar ratio, whereas in the
presence of excess aldehyde, the reaction yields a double-aldol
condensation product. This nucleophilic addition reaction
occurs in the presence of a base catalyst, where a carbon−
carbon bond is formed between compounds containing a
carbonyl group.7−10
Several undergraduate organic chemistry experiments
involving synthesis and analysis of aldol products have been
executed and published in recent years. One aldol experiment
employs green chemistry concepts, in which students use
cinnamaldehyde isolated from cinnamon to create an aldol
product.11 Another focuses on optimization of the aldol
condensation reaction in the undergraduate lab using two
Received: June 2, 2021
Revised: August 14, 2021
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relatively accessible reagents, vanillin and cinnamaldehyde
from cinnamon bark.12 The main objective in this project
compared to other procedures in the literature, including those
mentioned previously, is the in-depth analysis of the aldol
Scheme 1. General Reaction Scheme for an Aldol Condensation Reaction
Figure 1. Acetone with different types of benzaldehyde derivatives to produce dibenzalacetone derivatives. The compounds were produced from
the following benzaldehyde: (1) benzaldehyde, (2) p-tolualdehyde, (3) 4-ethylbenzaldehyde, (4) 2,4-dimethylbenzaldehyde, (5) 4-
fluorobenzaldehyde, and (6) 4-anisaldehyde.
Figure 2. Recrystallized dibenzalacetone products: (A) compound 1, (B) compound 2, (C) compound 3, (D) compound 4, (E) compound 5, and
(F) compound 6. The crystals have different shades of yellow and different textures.
Figure 3. Gas chromatogram for dibenzalacetone. The major peak (C) present in the GC at retention time 11.69 is the most stable trans−trans
isomer. The peak (A) at retention time 3.49 min represents the 1:1 aldehyde/ketone aldol product, and the peak (B) at retention time 9.86 min
represents the cis−cis isomer. Peaks A and B were assigned by similarity search. The trans−cis isomer was not present in this chromatogram.
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products using gas chromatography−mass spectrometry (GC−
MS) and the presentation of instrumental details relating to the
gas chromatogram−mass spectrometer. In this experiment,
students were directed how to dissect information from GC
and MS spectra to determine the success of their reaction,
purification methods, and so on. By analyzing GC, students
discovered that they produced a mixture of products, not just
the desired aldol product. By analyzing MS, students learned
about how fragmentation occurs, how to analyze mass spectra,
and how to draw fragment ions. 13C NMR, distortionless
enhancement by polarization transfer (DEPT) 90, and DEPT
135 NMR spectra were also collected for each product, as
typically 1H NMR data are the only NMR data included in
research literature involving the aldol condensation. Collecting
these NMR spectra also allowed students to review the
practical use of NMR to identify or confirm the identity of a
compound.
Figure 4. Possible compounds present in the final synthesis of dibenzalacetone.
Figure 5. Structure of the 4-ethylbenzaldehyde aldol product with aromatic rings, shown with (A) ethyl branches hanging out of each benzene ring,
gives the molecular ion peak. After removing an ethyl substituent, the fragment with m/z 261 is formed. By breaking down the compound through
α cleavage, the fragment with m/z 159 is formed.
Figure 6. Mass spectrum of the aldol product of 4-ethylbenzaldehyde and acetone.
Figure 7. Formation of the radical cation of the molecular ion peak.
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■ EXPERIMENT OVERVIEW
This experiment required 6 h, spanning over 2 weeks of the
organic lab course, and was conducted by four separate lab
sections of a second semester introductory organic chemistry
course in fall 2020 and spring 2021, with a total of 30 students
participating. Because of COVID-19, spring 2021 class
capacities allowed 12 students maximum, and students were
required to work individually. At the beginning of the lab
period in the first week, students were given a pre-lab
acknowledgment assessment, which contained 10 knowledge-
based questions pertaining to the aldol reaction and
calculations and eight knowledge-based questions about
usage and importance of GC−MS. During the first laboratory
session, students were assigned one of six benzaldehydes,
either benzaldehyde, p-tolualdehyde, 4-ethylbenzaldehyde, 4-
anisaldehyde, 2,4-dimethylbenzaldehyde, or 4-fluorobenzalde-
hyde, and were given acetone as the ketone, as shown in Figure
1. The aldol reaction was carried out in the presence of sodium
hydroxide, as described in the procedure provided in the
Supporting Information. Before synthesis, students had to
calculate the volume of aldehyde and ketone needed for the
reaction based on the reaction’s given molar ratios. This
reinforced general chemistry calculation knowledge that
requires finding the volume of each reagent required for the
reaction using density values and then determining the
theoretical yield based on the molar ratio of the reaction.
Since each student received a different benzaldehyde derivative
with a different density, they had to do the calculations
individually, as well.
During the synthesis, each student obtained a yellow-hued
product, as seen in Figure 2, which differed based on the
benzaldehyde derivative used due to the variability of the
conjugation of the final product. Students got a chance to
review the concept of conjugation, which describes the
alternating single and double bonds that create a conjugated
π bond system across multiple atoms and in turn stabilize the
molecule. Students understood that the product they
synthesized had a conjugated system of electrons, in which
the ground states and excited states of the electrons are closer
in energy than for nonconjugated systems. This means that
lower energy light, such as visible light, is sufficient to excite
electrons in conjugated systems. In addition, students were
taught the theory behind sunscreen compounds, as dibenza-
lacetone products are found in some sunscreen formulations.
Conjugated compounds like dibenzalacetone are sometimes
used as active ingredients in sunscreen because they absorb the
UV light and by doing so prevent most UV absorption by the
skin.
After the crude aldol product was synthesized, further
purification of the product was conducted using recrystalliza-
tion with ethanol, and the recrystallized product was left to dry.
During the second week, the final products were analyzed by
melting point, thin layer chromatography (TLC), and
spectroscopy and spectrometry. Students were given printed
handouts containing 1H NMR, 13C NMR, and DEPT spectra,
including DEPT 135 and DEPT 90. Students were also given
GC and MS data for their given product. GC−MS and NMR
data were gathered outside of classroom time by the professor
and her research students.
Students spent approximately 2 h of the 3 h classroom time
during week two analyzing GC−MS data. To begin GC−MS
data analysis, students identified the peaks in their compound’s
GC spectrum. Most students were expecting a single peak in
the GC, indicating the presence of their pure aldol product
rather than the many peaks present in each gas chromatogram.
An example of an impure GC spectrum of dibenzalacetone is
shown in Figure 3.
As a class, other compounds that could be present in the GC
spectra were discussed, and students were shown how to
conduct a similarity search for a given mass spectrum to
determine the possible identity of a GC peak. Some of them
observed monobenzaldehyde and acetone derivatives and
geometric isomers of the dibenzalacetone derivative products,
as shown in Figure 4. Students were reminded of the different
types of geometric isomers and discussed the relative stability
of each isomer. The trans−trans isomer was agreed to be the
most stable, and other isomers like trans−cis and cis−cis were
determined possible to form with small percentages.
Discussion of isomers was purely for brainstorming nonmajor
product peaks in the GC spectra. Students were not expected
to identify each type of isomer, as some isomers were not
present in the GC spectra.
Students were then tasked to analyze the mass spectrum of
the most abundant compound in the gas chromatogram, the
trans−trans aldol product. Mass spectra of other compounds
present in the GC spectra were ignored so that students could
focuson the fragmentation of their major product. To
understand fragmentation more clearly, each student analyzed
Figure 8. Cleavage of the side chain to form one possible fragment.
Figure 9. α Cleavage of the aldol product results in an acylium ion.
Figure 10. Formation of a fragment after removing the −CO group
from the acylium ion.
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and discussed their GC−MS reports, creating a molecular
model for each structure. Example models of fragments of the
4-ethylbenzaldehyde aldol product are shown in Figure 5.
Making a model of each product was beneficial to the
experiment because it helped the students understand how the
fragmentation occurred in different positions of the compound.
As expected by the fragments produced with the model kits,
the mass spectrum of the aldol product of 4-ethylbenzaldehyde
and acetone shows a molecular ion peak at m/z 290, a base
peak at m/z 261, and another prominent peak at 159. Other
prominent peaks are visible at m/z 131, m/z 91, and m/z 77, as
shown in Figure 6.
Fragmentation at m/z 290 is the molecular ion peak of the
4-ethylbenzaldehyde aldol product, and students drew the
structure as a radical cation for their own compound. All of the
students easily identified the molecular ion peak related to
their final product. The ion source in the GC−MS that forms
ions is electron ionization (EI). The electrons created by the
EI source have high energy that is used to remove an electron
of the gas phase of the compound. This ionization forms the
charged molecular ion, M+•, as shown in Figure 7.
Fragmentation at m/z 261 results from removal of the side
ethyl group (m/z 29) attached to the benzene ring. Most
students found the base peak by removing the side chains
attached to the benzene ring, as shown in Figure 8.
Then all students focused on α cleavage, in which the bond
linking the carbonyl carbon to the atom occupying an α
position breaks off the final aldol product, resulting in a
resonance-stabilized acylium ion, as shown in Figure 9.
Not all possible fragments created by the students were
visible in the mass spectra, and students were reminded that
fragments result from the positively charged species, while
neutralized or radical species are not detected by the mass
analyzer, as the separation of species by the mass spectrum
depends on deflection by a magnet. Neutral or radical species
would not be separated by mass and charge when traveling
through two poles of a magnet like charged species are. As a
result, charged speciesand specifically positively charged
species when using EI ionizationare the only species
detected by the mass spectrum analyzer. To be able to identify
all major fragments, students also learned about different
fragmentation patterns and methods of cleavage. After learning
about α cleavage, most students were able to produce an
acylium ion fragment. Students also observed a fragment after
removing the −CO group from the acylium ion, as shown in
the Figure 10.
According to the literature of aldol synthesis, students often
get the chance to analyze 1H NMR spectroscopy. In this
experiment, students similarly analyzed 13C NMR, DEPT 135,
and DEPT 90 to identify all types of carbons in the compound.
This is the first time in the lab that students were exposed to a
practical application of DEPT NMR technique.
The DEPT 135 and DEPT 90 were used in conjunction with
the 13C NMR to identify each carbon as a primary, secondary,
tertiary, or quaternary carbon. Using all of these types of C
NMR methods, students could identify all types of carbons
present in their final aldol product. For example, the overlay of
13C NMR, DEPT 90, and DEPT 135 for the 4-anisaldehyde
aldol product is shown in Figure 11.
Students were shown how to analyze the 13C NMR spectra
using theoretical chemical shift ranges of different types of 13C.
Students were able to utilize the theoretical chemical shift
ranges to identify the carbonyl carbon, aromatic and alkenyl
carbons, as well as the alkyl substituent carbons. Students were
also encouraged to utilize the different NMR techniques, such
as DEPT 90 and DEPT 135, when identifying the carbons in
Figure 11. Overlay of 13C NMR, DEPT 90, and DEPT 135 of the aldol product of 4-anisaldehyde and acetone. A peak is present for all eight
chemically non-equivalent 13C nuclei. Methoxy −CH3 carbon shifted at 55 ppm, carbonyl carbon shifted at 169 ppm, and aromatic carbons shifted
in the range of 142−123 ppm.
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their compound. DEPT is used for distinguishing between a
CH3 group, a CH2 group, and a CH group. DEPT 90 and
DEPT 135 spectra do not show quaternary carbons in the
molecule. DEPT 90 shows only R-CH carbons. In DEPT 135,
R-CH2 carbons are shown with a negative signal, and R-CH3
and R-CH carbons are shown with a positive signal. Students
could use this knowledge to differentiate between the sp3-
hybridized carbons of the ethyl substituents in the 4-
ethylbenzaldehyde aldol product, for example, since the two
signals have a similar chemical shift. The CH2 signal of the
ethyl group would be phased down, whereas the CH3 signal of
the ethyl group would be phased up in the DEPT 135
spectrum.
Students also performed TLC analysis using silica plates and
a mobile phase consisting of 20%:80% ethyl acetate/hexane.
The Rf values of the aldol products were compared to each
other to determine the compounds’ relative polarities. The p-
anisaldehyde aldol product had the lowest Rf value of 0.27,
indicating it was the most polar product of the six synthesized
compounds. The 2,4-dimethylbenzaldehyde and 4-ethylben-
zaldehyde aldol products had the highest Rf value of 0.72,
indicating they were the least polar. The benzaldehyde, 4-
fluorobenzaldehyde, and p-tolualdehyde aldol products had Rf
values of 0.69, 0.57, and 0.61, respectively. These data were
consistent with theoretical knowledge of compound polarity as
the p-anisaldehyde product contains more polar bonds than
the five other compounds and should therefore have the
smallest Rf value.
Further, students analyzed the recrystallized products by
melting point analysis using Vernier Melt Stations and
LabQuest sensors. Students recorded the melting point range
by determining the temperature at which the solid first started
melting and the temperature atwhich the solid was fully
melted. Students were shown how to draw their product’s
structure in SciFinder to find its theoretical physical property
data, such as melting point. Students then compared their
experimental melting point ranges to the theoretical melting
point of their product. Theoretical melting points for the 4-
ethylbenzaldehyde and 4-fluorobenzaldehyde aldol products
were not available on SciFinder or any other literature search.
We also discussed as a class the many reasons why an
experimental melting point can differ from a theoretical
melting point, such as impurities, improper recrystallization
technique, atmospheric conditions, and so on.
■ HAZARDS
Standard precautions for undergraduate laboratory students
were observed, such as safety goggles and gloves. Reagents
should be handled with caution. General risks include irritation
to the skin, eyes, respiratory tract, and digestive tract. This
reaction should be conducted in a fume hood. Compounds
used in the aldol condensation reaction are hazardous to the
eyes, skin, respiratory tract, and digestive tract.
Figure 12. Comparative percentages of students who answered pre- and post-lab acknowledgment assessment questions correctly, organized from
least improvement to greatest. Pre-lab percentages are represented in black, negative change in the post-lab quiz in blue, and positive change in the
post-lab quiz in green. The sample size of students who took the quiz was 30.
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■ EVALUATION OF LEARNING OBJECTIVES
To determine the effectiveness of the lab as a teaching tool, a
knowledge assessment of multiple-choice questions over
relevant content was administered both before and after the
lab, which spanned over 2 weeks total. The percentage of
students who answered correctly were analyzed on a question-
by-question basis, as seen in Figure 12. The greatest individual
increase in questions answered correctly was question 18,
which required students to draw the radical cation of the
parent molecule, seeing a rise of 47% correct from pre- to post-
lab. Overall, there was an average increase of 16% per student
from their pre-lab average of 73.66% to post-lab quiz grades,
which average 89.66% correct. Questions 13 and 15, which
required knowledge about the uses and components of GC−
MS, were the only questions answered incorrectly more often
on the post-lab quiz compared to the pre-lab quiz. Perhaps a
greater focus on practical uses of GC−MS, such as the different
industries that utilize it as well as a run-down of the schematic
of the GC−MS, would have prevented confusion and provided
more background information on the instrument. All-in-all, the
students’ abilities to answer more questions correctly relating
to the aldol condensation reaction and GC−MS after
completing the experiment demonstrated an increase in
knowledge of these topics over the course of the 2 week
experiment.
■ CONCLUSIONS
The aldol condensation reaction is a widely utilized C−C
coupling reaction taught in second-semester organic chemistry
laboratories. During this experiment, the reaction was
performed by students using a variety of benzaldehyde
derivatives and acetone to produce dibenzalacetone derivatives.
The aldol products were then analyzed by some of the most
relevant organic chemistry analytical methods, such as GC−
MS. This experiment strengthened students’ abilities to utilize
spectroscopic and spectrometric data, specifically GC−MS to
analyze samples synthesized in the lab. The nature of the
experiment, using different reactants to produce different
products, required students to think independently, complete
their own calculations, and perform their own reaction. The
pre- and post-lab questions administered to the students to test
their knowledge of the aldol condensation and GC−MS
demonstrated that students’ knowledge of these topics
improved over the course of 2 weeks in which this lab was
conducted. Students were also able to apply their knowledge of
NMR learned in organic chemistry lecture to their own
synthesized aldol product, allowing them to understand the
practicality and usefulness of NMR when identifying organic
molecules. The students also successfully identified peaks and
fragments of the product by GC−MS. Since this lab focuses
heavily on spectrometric and spectroscopic analysis, this
procedure could be utilized in any organic class where an
increased understanding of GC−MS and NMR is desired. This
lab demonstrated to students the power of chromatography
and mass spectrometry to separate and identify synthesized
compounds, while strongly reinforcing lecture concepts
relating to fragmentation and NMR peak identification.
Further, this experiment facilitated a deeper understanding of
instrumental methodologies used for organic analysis by
promoting student engagement and independent thinking by
requiring students to conduct their own experiment and
analyze their own unique compound.
■ ASSOCIATED CONTENT
*sı Supporting Information
The Supporting Information is available at https://pubs.ac-
s.org/doi/10.1021/acs.jchemed.1c00595.
Lab learning objectives (LLOs) (DOCX, PDF)
Student lab handout (DOCX, PDF)
Pre-lab knowledge assessment (DOCX, PDF)
Post-lab knowledge assessment (DOCX, PDF)
GC−MS data (DOCX, PDF)
NMR data (DOCX, PDF)
■ AUTHOR INFORMATION
Corresponding Author
Anuradha Liyana Pathiranage − Department of Chemistry,
Austin Peay State University, Clarksville, Tennessee 37044,
United States; orcid.org/0000-0003-3701-8151;
Email: pathiranagea@apsu.edu
Authors
Hailey N. Lynch − Department of Chemistry, Austin Peay
State University, Clarksville, Tennessee 37044, United States
Austin H. Harnage − Department of Chemistry, Austin Peay
State University, Clarksville, Tennessee 37044, United States
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.jchemed.1c00595
Notes
The authors declare no competing financial interest.
■ ACKNOWLEDGMENTS
This work was supported by the Austin Peay State University
Chemistry Department’s operating budget. We would like to
thank all of the students who participated in Organic
Chemistry II laboratories in fall 2020 and spring 2021. We
would like to thank Leslie Hiatt from Austin Peay State
University’s Chemistry Department for the invaluable
assistance using GC−MS.
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