In the Laboratory
Carbocation Rearrangement in an Electrophilic
Aromatic Substitution Discovery Laboratory
Victoria Polito, Christian S. Hamann, and Ian J. Rhile*
Department of Chemistry and Biochemistry, Albright College, Reading, Pennsylvania 19612-5234
*irhile@alb.edu
Rearrangements are an iconic feature of carbocations. A
hydrogen or alkyl group and its electrons migrate to the electron
deficient center to form a more stable carbocation in such a
carbocation rearrangement, often called Wagner-Meerwein
rearrangement. Classic studies compared the migratory aptitudes
of different groups and NMR studies of isotopically labeled
substrates (1). Computational and gas-phase investigations re-
veal the involvement of nonclassical carbocations such as proto-
nated cyclopropanes (2). Reaction in solution can change the
potential energy surface through solvation of the intermediates.
Most introductory and advanced textbooks cover these
rearrangements (3-7). However, only a few introductory organic
laboratory experiments illustrate these rearrangements (8-13). Of
the experiments that allow students to synthesize a product of
rearrangement, two involve epoxide rearrangements (10, 11) and
another involves a Ritter reaction (12), all of which most intro-
ductory textbooks do not cover. Another involves a steroid system
with an involved NMR analysis (13). We report a laboratory
experiment on electrophilic aromatic substitution that includes a
rearrangement with a product that can be completely characterized
with 1H and 13C NMR and infrared spectroscopies and mass
spectrometry.
Electrophilic aromatic substitution represents the most
important reaction type of aromatic compounds presented in
undergraduate organic chemistry courses. A common laboratory
experiment illustrating the reaction is the alkylation of 1,4-
dimethoxybenzene with tert-butanol and sulfuric acid in acetic
acid (14). Under the conditions of the experiment, two tert-butyl
groups replace hydrogen atoms of the aromatic compound to
form 2,5-di-tert-butyl-1,4-dimethoxybenezene. Students justify
the number of substitutions using steric effects and justify the
substitution pattern using directing effects.
In our modification of this laboratory, students perform two
reactions (Figure 1). One group of students reacts 1,4-dimethox-
ybenzene with 2-methyl-2-butanol, while the other group reacts
1,4-dimethoxybenzene with 3-methyl-2-butanol. Both reactions
give 1,4-bis(1,1-dimethylpropyl)-2,5-dimethoxybenzene. The re-
arrangement parallels other rearrangements in the literature (15).
The students do not know the identity of the reaction products,
but must determine the products via 1H NMR, 13C NMR,
GC-MS, and infrared spectra. Students compare the spectra of
both reactions to determine that the products are identical and
that one reactant alcohol underwent rearrangement. Hence, it is
a discovery laboratory (16).
Experiment
In the laboratory, students suspend 1,4-dimethoxybenzene
and their alcohol in glacial acetic acid in an Erlenmeyer flask
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r 2010 American Chemical Society and Division of Chemical Education, Inc. pubs.acs.org/jchemeduc Vol. 87 No. 9 September 2010
10.1021/ed9000238 Published on Web 07/08/2010
equipped with a stir bar. The slurry is chilled in an ice-water
bath, and sulfuric acid is added over a 10-15 min period via a
mounted separatory funnel below eye level. After stirring for
20 min, ice or ice-cold water is carefully added to the flask and the
solid is filtered. Recrystallization from ethanol provides white
plates. A complete procedure with safety precautions is given in
the supporting information. Students obtain 1H NMR, 13C
NMR, infrared, and mass spectra, and a melting point during the
second week of laboratory. Students obtain data from a partner
who used the other alcohol for the experiment. Instructors could
provide spectra or a molecular formula if one or more of these
instruments are unavailable. Instructors encourage students to
discuss their spectra before leaving laboratory. Students can
complete work within two 3- or 4-h laboratory periods.
Hazards
Students employ concentrated sulfuric acid (17) and glacial
acetic acid (18) for this laboratory. Concentrated acids are highly
corrosive. All spills should be treated with sodium bicarbonate,
and exposed skin should be flushed for at least 20 min followed
by immediate medical attention. 2-Methyl-2-butanol and
3-methyl-2-butanol are flammable and may cause skin or eye
irritation upon contact. 1,4-Dimethoxybenzene is an irritant and
is combustible.
Results and Discussion
Students can readily determine the product identity with
spectroscopic and physical characterization data. Comparison of
all data establishes that both compounds are identical. (The
melting points for the products of the two reactions may differ by
4 °C, but are close enough to establish an identical structure.1
The gas chromatogram indicates a small quantity of impurity in
Figure 1. Electrophilic aromatic substitution reactions of 1,4-dimethox-
ybenzene with different alcohols that produce the same product.
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Journal of Chemical Education 969
 In the Laboratory
the product from 2-methyl-2-butanol.) The molecular ion in the
mass spectrum indicates that two C5H11 groups have substituted
for two hydrogen atoms in the starting material. The ratio of
aromatic proton integrations to the various alkyl proton integra-
tions in the 1H NMR also confirms the disubstitution. The
singlet at 6.74 ppm in the 1H NMR, the three absorptions at 152,
135, and 113 ppm in the 13C NMR, and the aromatic carbon-
carbon bond stretch at 1506 cm-1 indicate that the aromatic ring
is preserved from the starting material. The singlet at 3.78 ppm in
the 1H NMR and the absorption at 56 ppm in the 13C NMR
indicate that methoxy absorption is preserved as well and that they
are equivalent in the product. The infrared spectrum indicates a
lack of carbonyl or hydroxyl groups. These data eliminate a phenol
as a possible structure.
The NMR spectra establish the tert-pentyl group. Three
hydrogen environments and four carbon environments establish
a degree of symmetry in the alkyl group. The triplet at 0.64 ppm
and quartet at 1.79 ppm at an integral ratio of 2:3 establish an
ethyl group, and a singlet at 1.31 ppm establishes two equivalent
methyl groups. The only connectivity pattern consistent with
C5H11 and these splitting and integral patterns is a tert-pentyl
group. A peak at charge-to-mass ratio of 249 is consistent with
loss of an ethyl group from the molecular ion. The product from
unrearranged 3-methyl-2-butanol is excluded based on the 1H
and 13C NMR.
Although it appears to students that each alcohol provides a
unique product, after incorporating this data, the symmetry implied
by the 13C NMR indicates that only 1,4-bis(1,1-dimethylpropyl)-
2,5-dimethoxybenzene and 1,2-bis(1,1-dimethylpropyl)-3,6-dimeth-
oxybenzene are possible isomers of the product. Any physical or
computational molecular model readily indicates that adjacent tert-
pentyl groups are unfeasible. Hence, 1,4-bis(1,1-dimethylpropyl)-
2,5-dimethoxybenzene is the only reasonable product.
We implemented this laboratory in the second semester of
introductory organic chemistry to illustrate carbocation chem-
istry and electrophilic aromatic substitution. This laboratory
could also be used in an upper-level course with the extensive
literature on the pentyl cation potential energy surface.2 The
laboratory provides a basis to use inductive reasoning with
spectral data to determine a structure and serves as an introduc-
tion to mechanistic work.
Acknowledgment
The Albright Creative Research Experience program pro-
vided funding for this work. We would like to thank Beth
L. Buckwalter and Ryan A. Mehl of Franklin and Marshall
College for initial NMR spectra.
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970 Journal of Chemical Education Vol. 87 No. 9 September 2010
Notes
1. A reviewer recommended a mixed melting point for further
verification that the compounds are identical.
2. Interestingly, the protonated cyclopropane is calculated to be
more stable that the 3-methyl-2-butyl cation (2).
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Supporting Information Available
Notes for the instructor; instructors for the student; representative
data. This material is available via the Internet at http://pubs.acs.org.
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pubs.acs.org/jchemeduc r 2010 American Chemical Society and Division of Chemical Education, Inc.