In the Laboratory
pH-Controlled Oxidation of an Aromatic Ketone:
Structural Elucidation of the Products of Two Green
Chemical Reactions
C. Eric Ballard*
Department of Chemistry and Physics, University of Tampa, Tampa, Florida 33606-1490
eballard@ut.edu
The second-semester organic chemistry laboratory at this
university used to rely heavily on cookbook-type experiments
that included little characterization of reaction products. More
research- and discovery-oriented experiments were desired to
improve the course (1). Ideally the new experiments would meet
several criteria: (i) use newly acquired instruments, a high-field
NMR and GC-MS, to characterize the reaction products; (ii)
provide illustrations of key concepts such as selectivity; (iii) allow
for discussions of reaction mechanisms; and (iv) demonstrate
principles of green chemistry (2). An experiment incorporating
all of these components is described.
Experiment
This experiment involves a pair of reactions (Figure 1) using
the same substrate, 40 -methoxyacetophenone, and the same
reagent, sodium hypochlorite (household bleach). The difference
between the reactions is the pH at which they are conducted.
When the starting material is heated with bleach (pH 11-12), a
haloform reaction (3) oxidatively cleaves a carbon-carbon bond
to form 4-methoxybenzoic acid as the product. When the
substrate is stirred with acetic acid and bleach (pH 4) at room
temperature, electrophilic aromatic substitution (4) occurs to
generate 30 -chloro-40 -methoxyacetophenone as the product.
Although the haloform reaction is precedented in the pedago-
gical literature (3d), this experiment differs because it is dis-
covery-oriented and it includes a new reaction for the teaching
lab, aromatic chlorination. The development of this experiment
was inspired by a chemoselective bromination of acetophenones
conducted without organic solvent (5).
The hypochlorite present in the bleach is in equilibrium
with other species, including hypochlorous acid and molecular
chlorine (Figure 2) (4b). Since the pH of the haloform reaction
mixture is much higher than the pKa of hypochlorous acid (7.53)
(6), hypochlorite is the major species present at equilibrium.
Because the pH of the electrophilic chlorination mixture is much
lower than the pKa, the major species is hypochlorous acid.
Chlorine (or a similar reactive species) that is in equilibrium with
these species probably acts as the active oxidizing agent in both
reactions (4a, 4b). Bleach is a safe reagent for producing low
concentrations of chlorine.
Both reactions are short (30 min) and require simple
extraction-free workups to obtain the products as pure solids
in high yield; students may achieve yields near 90%. After the
students have determined the experimental yields of their
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190 Journal of Chemical Education Vol. 87 No. 2 February 2010
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products, they can collect data to help them identify the
compounds. The data collection includes mp, 1H and 13C
NMR, IR, and GC-MS spectra and chromatograms. Given
the quantity of data that must be collected, it is recommended
that the experiment span two lab periods, that students collect
only a portion of the data and share it, or that the instructor
provide some of the data to the students.
Hazards
These reactions should be performed in a fume hood
because of the strong odors evolved during the experiments.
40 -Methoxyacetophenone may cause eye, skin, respiratory, and
digestive tract irritation. Sodium hypochlorite is corrosive.
Glacial acetic acid is a dehydrating agent and an irritant and is
corrosive. Avoid contact of skin and eyes with sodium thiosulfate
solution. 30 -Chloro-40 -methoxyacetophenone and 4-methoxy-
benzoic acid are irritants. Chloroform may be fatal if swallowed,
inhaled, or absorbed through skin, and it causes irritation to skin,
eyes, and respiratory tract. Chloroform is reasonably expected to
be carcinogenic. Dispose of wastes in the appropriate containers.
Results and Discussion
This experiment involves reactions that are relatively easy to
execute but challenge the students with spectral interpretration.
To help students with the identification of the reaction products,
they are encouraged to start by assigning the 1H NMR spectrum
of the substrate of the reactions. Assignment of the spectrum of
40 -methoxyacetophenone is a good starting point for identifying
the products because it can be compared with the products' 1H
NMR spectra. The 1H NMR spectra of the three compounds are
shown in Figure 3. Spectrum A of the substrate consists of two
resonances in the aromatic region and two singlets farther upfield
corresponding to the methyl groups. Spectrum B of the car-
boxylic acid shows the aromatic protons and the ether methyl,
but it lacks the resonance of the acetyl methyl; this indicates that
the functional group changed during the reaction. Indeed, the
haloform reaction oxidized the ketone to a carboxyl group.
Spectrum C of the ring-chlorinated product shows the reso-
nances of both methyls, but it shows the presence of only three
aromatic protons; this indicates the aromatic ring changed
during the reaction. The mass spectrum of the chlorinated
product shows a ∼3:1 ratio of the M/M þ 2 signals at m/z
184 and 186, indicating the presence of a single chlorine atom in
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pubs.acs.org/jchemeduc r 2010 American Chemical Society and Division of Chemical Education, Inc.

Figure 1. Reactions of 40 -methoxyacetophenone with bleach in the
presence of base and acid.
Figure 2. Equilibria involving hypochlorite that affect the major species
present in bleach.
the product (the supporting information includes full character-
ization data). These data are evidence that a chlorine atom
substituted on the aromatic ring during the reaction.
The differences in the reaction products provide an oppor-
tunity to discuss the ideas of chemo- and regioselectivity.
Chemoselectivity is illustrated by the reactivity of different func-
tional groups under the different reaction conditions (Figure 4).
Under the basic conditions of the haloform reaction, the methyl
ketone enolizes, resulting in a stronger nucleophile than the
aromatic ring; the enolate nucleophile attacks the chlorine
electrophile resulting in R-haolgenation of the ketone moiety.
Exhaustive R-chlorination of the methyl group followed by
nucleophilic acyl substitution of the trichloromethyl group by
hydroxide yields the carboxylate product. In contrast, under the
acidic conditions of the electrophilic aromatic chlorination, the
ketone does not enolize readily; the aromatic ring activated by
the methoxy group is the nucleophile that reacts with chlorine.
The aromatic chlorination illustrates the concept of regio-
selectivity. The reaction occurs exclusively ortho to the ether
instead of ortho to the ketone. Most students can assign the
correct regiochemistry of the chlorine by considering the direct-
ing effects of each substituent.
These two reactions also provide an opportunity to discuss
redox reactions in the context of organic chemistry. It is obvious
to most students that the haloform reaction is an oxidation
because the product contains more oxygen atoms than the
substrate. It is less apparent that the electrophilic aromatic
substitution is an oxidation since no oxygen was added to form
the product. However, this reaction is also an oxidation because
the product contains a new bond between carbon and an atom
that is more electronegative than carbon; a carbon-chlorine
bond replaced one of the carbon-hydrogen bonds of the
aromatic ring. Since both reactions are oxidations, this experi-
ment illustrates the breadth of redox processes in organic
chemistry.
Regarding assessment, students usually have difficulty start-
ing the spectral interpretation and feel overwhelmed. As they
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r 2010 American Chemical Society and Division of Chemical Education, Inc.
In the Laboratory
Figure 3. Comparison of the 1H NMR spectra of (A) the substrate, (B) the
haloform product (X in Figure 1), and (C) the chlorination product (Y in
Figure 1).
discuss the data with the instructor, they gain more confidence in
their problem-solving strategies. Almost all students correctly
identify the two products in their lab reports, and most of them
use the spectral data to provide strong support for their conclu-
sions. About 10% of students rationalized the regiochemistry
from the 1H NMR spectrum by considering resonance forms of
the product. However, the 1H and 13C NMR spectra are
insufficient for making a definitive assignment of the location
of the chlorine substituent. The author is unsure how much
spectral interpretation each student performs and how much
information is exchanged among students after a small group of
them have solved the products' structures.
The students' understanding of the reaction mechanisms
depends on when the experiment is performed in relation to the
coverage of course topics. The author and his colleagues have
performed the experiment before the introduction of electro-
philic aromatic substitution or enolate halogenation in lectures.
However, by the time the students' reports were due, the former
topic had been discussed in the classroom, and students under-
stood that the chlorination was an example of an electrophilic
aromatic substitution.
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 In the Laboratory
Figure 4. Mechanisms of the two reactions.
Besides being used in the second-semester organic labora-
tory, this experiment is also appropriate as an early experiment of
an advanced or third-semester organic laboratory. Because the
reactions are operationally simple, the instructor can emphasize
the opportunity for students to become (re)acquainted with the
hands-on operation of several instruments. In addition, the
experiment reinforces the concepts of reactivity, selectivity, and
spectral interpretation that were introduced in the second-
semester organic course.
Green Chemistry
This experiment also demonstrates some of the principles of
green chemistry (2): performing less hazardous chemical synth-
eses, using safer solvents, and using safer chemistry to reduce
accidents. These reactions involve bleach, a household chemical,
as the reagent. This reagent is safer to handle than other oxidants
and halogenating agents, such as chromium- and manganese-
based reagents, gaseous chlorine or liquid bromine, sulfuryl
chloride, and 2-iodoxybenzoic acid (7). The reactions are con-
ducted using water and acetic acid as the only solvents, and no
organic solvent is required to work up or extract the products.
The electrophilic aromatic substitution does not require a Lewis
acid promoter. Although this experiment demonstrates only a
few of the principles of green chemistry, it is greener than the
alternatives of using harsher reagents or additional solvents (8).
Acknowledgment
The author thanks his colleagues who taught this experi-
ment and provided helpful feedback during its development:
Scott Allen, John Struss, Donald Cannon, and Michael Carastro.
He also thanks Ken Doxsee and Jim Hutchison for his participa-
tion in a Green Chemistry in Education Workshop at the
University of Oregon.
Literature Cited
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Ruttledge, T. R. J. Chem. Educ. 1998, 75, 1575–1577. (b) Davis,
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192 Journal of Chemical Education Vol. 87 No. 2 February 2010
D. S.; Hargrove, R. J.; Hugdahl, J. D. J. Chem. Educ. 1999, 76, 1127–
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Trahanovsky, W. S. In Oxidation in Organic Chemistry, Pt. C;
Academic Press: New York, 1978; pp 343-370. (d) Example
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Operational Organic Chemistry: A Problem-Solving Approach to the
Laboratory Course; Prentice-Hall: Upper Saddle River, NJ, 2002;
pp 322-328.
4. (a) Overview of halogenation of aromatic compounds: Smith, M. B.;
March, J. March's Advanced Organic Chemistry: Reactions, Mecha-
nisms, and Structure, 6th ed.; Wiley: Hoboken, NJ, 2007; pp
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(f) Example of an electrophilic aromatic iodination using bleach
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182-188. (g) Example of a discovery-oriented experiment
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 In the Laboratory

including electrophilic aromatic iodination using bleach as
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Supporting Information Available
Student handouts, including full experimental details, a prelab
worksheet, and postlab questions; notes for instructors; 1H and 13C
NMR, IR, and GC-MS spectra and chromatograms of the substrate
and the products. This material is available via the Internet at http://
pubs.acs.org.

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r 2010 American Chemical Society and Division of Chemical Education, Inc. pubs.acs.org/jchemeduc Vol. 87 No. 2 February 2010 Journal of Chemical Education 193