CHAPTER 19
AROMATIC COMPOUNDS I: AROMATICITY
AROMATIC SUBSTITUTION
ELECTROPHILIC
AND
19.1 INTRODUCTION
In 1825, Michael Faraday discovered a new hydrocarbon, later named benzene, in the
illuminating gas made from whale oil. The molecule has intrigued organic chemists since, and it
played a pivotal role in the development of structural theory in organic chemistry. Benzene is
the prototype of the class of compounds known as aromatic compounds. Historically, this term
referred to the fact that many aromatic compounds have pleasant odors – they are "aromatic" –
but this definition has now been superseded by a chemical definition based on structure and
reactivity instead of smell. Aromatic compounds comprise not only hydrocarbon derivatives, but
compounds in which the ring includes a heteroatom as well. Aromatic compounds are widely
distributed in nature, and they comprise a major percentage of drugs which are in use today to
treat disease. Some idea of just how widely aromatic compounds are distributed in our
environment may be gauged from the examples below.
CH3
SO2NH2
CHO
OH
NO2
CH3
OMe
toluene
(a gasoline
additive)
benzene
Cl
phenol
(carbolic acid –
the first antiseptic)
Cl
Cl
vanillin
(vanilla beans)
NHCOCH3
O 2N
NH2
OH
NO2
2,4,6-trinitrotoluene
(TNT – an explosive)
sulfanilamide
(an early sulfa
drug antibiotic)
CH2CH2OH
Cl
Cl
Cl
a polychlorinated biphenyl
(a PCB – now regulated as
toxic waste materials)
O
C
naphthalene
(mothballs)
OH
acetaminophen
(an analgesic)
NMe2
NEt2
O
N
Cl
chlorpheniramine
(antihistamine)
O
MeO
CH3
N,N-diethyl-m-toluamide
(DEET – a mosquito
repellant)
benzo[a]pyrene
(found in soot and tobacco
smoke tar – shown to
cause lung cancer)
MeO
MeO
N
2-phenylethanol
(artificial rose scent)
MeO
papaverine (one
component of the
opium poppy)
MeO
2-ethylhexyl
p-methoxycinnamate
(a sunblock component)
Nomenclature
The nomenclature of aromatic compounds is replete with a large number of well-entrenched
trivial names. The simplest aromatic compound is the hydrocarbon benzene. Under IUPAC
rules, the aromatic ring has approximately the same priority as a double bond. When the ring
bears a single substituent, the compound is usually named as a benzene with the substituent as a
AROMATIC COMPOUNDS I
Chapter 19 704
prefix. In those cases where the substituent bears a functional group higher than the aromatic
ring under IUPAC rules, the aromatic ring is named as a substituent. The substituent C6H5– is
called a phenyl group, often abbreviated as Ph; the substituent C6H5CH2– (the phenylmethyl
group) is called a benzyl group.
Phenyl groups and benzyl groups are often confused, so beware! Remember –
Phenyl groups are AROMATIC, and are bonded to the substituent through an sp2hybridized carbon atom; benzyl groups are ALIPHATIC, and are bonded to the
substituent through an sp3-hybridized carbon atom.
Simple alkyl derivatives of benzene are named as alkylbenzenes if the alkyl group is larger
than methyl; the methylbenzenes are usually known by their trivial names: methylbenzene is
known as toluene, and the isomeric dimethylbenzenes are known as xylenes. When there is
more than one substituent on the ring, substituted benzenes are names according to one of two
conventions. In the disubstituted benzenes, the isomer is ortho- or o-disubstituted if the
substituents are bonded to adjacent atoms in the ring, meta- or m-disubstituted if the
substituents are bonded to ring atoms separated by a single atom, and para- or p-disubstituted
if the substituents occupy positions diametrically opposite to each other on the ring.
ortho (o-) or 1,2-
M.D.
para (p-) or 1,4-
meta (m-) or 1,3-
M.D.
M.D.
M.D.
M.D.
M.D.
The designations ortho, meta, and para have given rise to a number of chemical word-games and puns
based on nomenclature. Examples of this kind of word game are the three structures shown here. If the
left-hand "compound" is "orthodox," can you deduce what the others are?
When the ring bears more than two substituents, it is usual to denote the positions of
substituents by numbers. Where the base name of the compound is benzene, the substituent
positions are assigned numbers so that the first two locants have the lowest possible numbers;
when the compound is named as a derivative of toluene or phenol, however, the position with
the number 1 on the ring is determined by the methyl group (in toluene) or the hydroxy group
(in phenol). TNT, above, is 2,4,6-trinitrotoluene, the aromatic rings of the PCB shown are both
1,2,4,5-tetrasubstituted, and vanillin is 4-hydroxy-3-methoxybenzaldehyde.
Disubstituted
benzenes can also be named by this convention: o-disubstitution is 1,2-disubstitution;
m-disubstitution is 1,3-disubstitution; p-disubstitution is 1,4-disubstitution.
Hydroxybenzene is known as phenol, although CAS uses benzenol, an alternative to the
IUPAC-approved root name of phenol. The trivial name of methylphenol is cresol.
Methoxybenzene is anisole, and this is a common root name for compounds based on the
methoxybenzene ring system. Aminobenzene, likewise, is best known as aniline, although
CAS® again uses the root name benzeneamine for substituted anilines. Aromatic ketones
where the carbonyl group is directly bonded to the ring are known as phenones, where the
prefix gives the name of the acyl group bonded to the ring. Benzaldehyde is both a trivial and
the accepted IUPAC and CAS® name for this compound.
Since many or most of these compounds have been instrumental in the development of
organic chemistry, it is important that you be able to name them based on the older
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
nomenclature, as well as the CAS® system. This also applies to polysubstituted benzenes. Some
of the more important simple benzene derivatives are given below, along with their IUPAC
names and their CAS® names in square brackets.
CH3
CH3
CH3
CH=CH2
CH3
CH3
o-xylene
[1,2-dimethylbenzene]
toluene
cathecol
[1,2-benzenediol]
NH2
resorcinol
[1,3-benzenediol]
O
C
H
HO
hydroquinone
[1,4-benzenediol]
anisole
[methoxybenzene]
O
NH2
OCH3
cumene
[2-phenylpropane]
OCH3
OH
OH
OH
phenol
styrene
[phenylethene]
mesitylene
[1,3,5-trimethylbenzene]
OH
OH
OH
CH3
C
CH3
benzaldehyde
O
NH2
C
CH3
aniline
[benzenamine]
o-anisidine
[2-methoxybenzenamine]
m-toluidine
[3-methylbenzenamine]
acetophenone
[1-phenylethanone]
benzophenone
[diphenylmethanone]
Sample Problem 19.1. Give a trivial name (if any) and an acceptable IUPAC name for
each of the following compounds. Where the CAS® name is different, give the CAS
name also.
CH2CH3
CH2OH
CH3
(a)
CH=O
(b)
(c)
CH=CH2
(d)
CH3
CH3
Br
Answers:
(a) ethylbenzene.
(b) trivial: o-tolualdehyde; IUPAC and CAS: 2-methylbenzaldehyde.
(c) trivial: 3,5-dimethylbenzyl alcohol;
IUPAC and CAS®: 3,5-dimethylphenylmethanol.
(d) trivial: m-bromostyrene; IUPAC and CAS®: 3-bromo-1-ethenylbenzene.
Problem 19.1. Give a trivial name (if any) and an acceptable IUPAC name for each of
the following compounds. Where the CAS® name is different, give the CAS® name,
also.
OH
(a)
(b)
CH3O
CH3
NH2
CH3
OH
(c)
(d)
OCH3
OCH3
(e)
OH
CHO
Problem 19.2. Give the IUPAC name of each of the following compounds, all of which
are better known by the trivial names given.
705
AROMATIC COMPOUNDS I
CO2H
H
H
(a)
Chapter 19 706
O
CO2H
(b)
H
CO2CH3
OH
OCH2CH3
(e)
(d)
(c)
OCH3
OCH3
OH
p-anisic acid
cinnamic acid
C
methyl salicylate
(oil of wintergreen)
phenetole
vanillin
Polycyclic aromatic compounds
Benzene is the simplest carbocyclic aromatic compound, and it contains a single aromatic ring.
There are, however, many aromatic compounds known whose structures are based on systems
of fused aromatic rings. The simplest of these hydrocarbons, known as polycyclic aromatic
hydrocarbons (or PCAH's), is naphthalene, which is bicyclic. There are two tricyclic PCAH's –
anthracene, which is a linear compound, and phenanthrene, in which the three aromatic rings are
fused in a non-linear orientation.
3
8
1
8
9
1
7
2
7
2
6
3
6
3
5
4
5
10
5
10
8
naphthalene
1
6
7
4
anthracene
2
4
9
phenanthrene
The linear PCAH's are known collectively as the acenes, so that the PCAH with four rings is
tetracene, that with five is pentacene, and so on.
tetracene
pentacene
Just as the numbering system of fused-ring and bridged-ring polycyclic alkanes is fixed by the
ring system rather than by the substituents, so the numbering system of the PCAH's is fixed by
the ring system. The numbering systems of the three simplest PCAH's are given above.
Heteroaromatic compounds
Benzene and its derivatives are most often used as the models for aromatic reactivity, but
there are numerous analogues of benzene which differ from it only by having one or more CH
groups substituted by a heteroatom. The simplest substitution of this type is the substitution of
one CH group of benzene by a nitrogen. This results in the important heteroaromatic amine
pyridine, which we have seen used over and over again as a base in reactions where acid is
produced. The pyridine ring is also an important structural component of many pharmaceuticals.
The substitution of two CH groups of benzene by nitrogen gives three different heterocyclic
amines: pyridazine, pyrimidine and pyrazine; pyrimidines occur naturally as components of RNA
and DNA, and the pyridazines and pyrazines have become important pharmaceutical and
agricultural chemicals. Just like the PCAH's, the numbering system of heterocyclic aromatic
compounds are determined by the ring system and the location of the heteroatom or
heteroatoms; the numbering systems of the heterocyclic aromatic compounds are given on each
of the structures shown.
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
4
4
5
6
N
1
3
5
2
6
pyridine
N
1
4
N
4
3
5
N2
6
pyridazine
N3
5
2
6
N
1
pyrimidine
3
2
N
1
pyrazine
These heterocyclic aromatic amines are all based on six-membered rings. However, when the
ring contains a heteroatom, the ring need not be six-membered in order for the compound to be
aromatic, as is shown by four aromatic compounds below where the heterocyclic ring contains
only five atoms. The first three of these compounds contain a single heteroatom in the ring:
pyrrole, where the heteroatom is nitrogen, furan, where the heteroatom is oxygen, and
thiophene, where the heteroatom is sulfur; the fourth compound, which contains two nitrogen
atoms in the ring, is imidazole. The imidazole ring system is an essential part of many biological
systems, including several important enzymes.
3
4
2
3
5
1
4
2
N
3
5
2
O
1
H
pyrrole
furan
3
4
S
1
N4
5
2
5
1
N
H
thiophene
imidazole
Heterocyclic analogs of the polycyclic aromatic hydrocarbons are also known, but except for
the three compounds shown below, quinoline and isoquinoline (based on naphthalene) and indole
(a sort of benzene-pyrrole hybrid) their chemistry is usually the subject of specialized textbooks in
heterocyclic chemistry.
5
4
5
4
4
6
3
6
3
5
7
2
7
N2
6
N
1
8
8
quinoline
2
N1
7
1
isoquinoline
3
H
indole
Problem 19.3. Draw the structure of each of the following compounds.
(a) 2-methylnaphthalene.
(c) 8-hydroxyquinoline.
(e) 2,3-diethylfuran.
(g) 5-fluoropyrimidine.
(b) 2-chloropyridine.
(d) 9,10-dimethylanthracene.
(f) 4,6-diaminophenanthrene.
(h) 1-methoxyisoquinoline.
Problem 19.4. Give an acceptable name for each of the following compounds.
CH3
(a)
(b)
N
CH3
Br
(c)
Br
S
(d)
CH3O
N
Physical properties
Benzene and the low-molecular weight alkylbenzenes are water-insoluble liquids at room
temperature, while the polycyclic aromatic hydrocarbons are solids. As expected, the boiling
points of alkylbenzenes increase with the molecular weight. The physical properties of the
heterocyclic aromatic compounds are fairly similar to what one would predict on the basis of
707
AROMATIC COMPOUNDS I
Chapter 19 708
molecular weight and polarity of the molecule. Pyridine is completely miscible with water,
pyrrole and furan are slightly soluble in water, and thiophene is insoluble in water.
Table 19.1 Physical Properties of Selected Aromatic Compounds
Compound
Molecular weight
m.p.
b.p.
benzene
toluene
ethylbenzene
phenol
aniline
anisole
nitrobenzene
naphthalene
furan
pyrrole
thiophene
pyridine
78
92
106
94
93
108
123
128
68
67
86
79
5
-95
-95
42-43
80
111
136
181
184
155
211
217
32
130
84
115
–
5-6
80
–
–
-38
-42
Spectroscopy
Aromatic compounds have an extended π electron system, so they absorb in the accessible
regions of the uv-visible spectrum. Most simple aromatic compounds exhibit two absorption
bands in the accessible region of the spectrum. The more intense of these two absorption bands
is known as the K band. It typically occurs at wavelengths below 250 nm for simple
monosubstituted benzenes, and it usually has a value of εmax above 5,000. The other band,
known as the B band, is a low-intensity band that occurs about 50 nm longer wavelength than
the K band; εmax values for the B band of simple substituted benzenes are seldom above 1,500.
Unfortunately, the uv-visible spectra of most simple aromatic compounds are not amenable to the
same analysis as the spectra of conjugated dienes and enones: there are no predictive rules as
simple as the Woodward Rules for predicting the value of λmax for simple aromatic compounds.
The infrared spectra of most aromatic compounds are characterized by the presence of weak
absorptions between 3000 and 3100 cm-1 due to stretching of C–H bonds of the aromatic ring.
More diagnostic in benzenes are the absorptions in the double bond region of the spectrum:
benzenes almost always give rise to a pair of strong absorptions near 1500 cm-1 and 1600 cm-1,
and a weak-to-medium intensity absorption between them. These absorptions are due to the the
in-plane deformation vibrations of the aromatic ring.
Perhaps the most diagnostic spectroscopic evidence for the presence of an aromatic ring in a
molecule is given by the 1H NMR spectrum, where the paramagnetic ring current of the
aromatic ring results in the aromatic protons being strongly deshielded. Protons directly bonded
to a simple aromatic ring typically resonate in the 6-8.5 ppm range, depending on the exact
nature of the aromatic ring itself and the substituents bonded to it. In general, protons bonded to
carbons where resonance would predict a low electron density tend to resonate downfield from
the unsubstituted compounds, while protons bonded to carbons where resonance would predict a
high electron density tend to resonate at higher field. The chemical shift of an aromatic proton
may thus be used as one parameter to estimate the electron density in an aromatic ring.
The sp2 carbons of most aromatic rings resonate between 115 and 145 ppm when the
substituent is not strongly electronegative, not appreciably different from the sp2 carbon
resonances of alkenes. The aromatic carbon nuclei resonate at somewhat lower field (130-160
ppm) when the substituent bonded to carbon is electronegative (such as an alkoxy or alkylamino
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
group). The 13C NMR spectrum of an aromatic compound is invaluable, however, in giving
information about the substitution pattern of the ring, and about the symmetry of the substitution
in particular, as was discussed at some length in Chapter 6.
The substitution pattern of aromatic rings was once assigned on the basis of the absorptions
between 500 and 1000 cm-1, due to out-of-plane wagging of aromatic hydrogen atoms. With the
advent of modern FT-NMR spectrometers, however, this method has become obsolete, and the
proton multiplicities in high-field 1H NMR spectra are now routinely used for obtaining
substitution patterns in aromatic compounds. This method is viable because the coupling
constants between protons fall into three well-defined ranges: ortho coupling constants are
typically between 6 and 8 Hz, meta coupling constants are usually between 2 and 3 Hz, and para
coupling constants are almost always less than 1.5 Hz.
19.2 STRUCTURE AND BONDING IN BENZENE: THE DEVELOPMENT
THE CONCEPT OF AROMATICITY
OF
Within ten years of its discovery by Faraday, benzene had been discovered in other sources
and synthesized from other compounds. In 1833, Eilhardt Mitscherlich established the molecular
formula of benzene as C6H6 by means of vapor density measurements; a year later he
synthesized benzene from benzoic acid and showed that it was identical to Faraday's
hydrocarbon. The empirical formula of benzene (CH) showed quite clearly that it is a highly
unsaturated compound – even more unsaturated than ethylene. And herein lay the problem for
organic chemistry – it did not fit the normal reactivity patterns that had begun to appear as a
means of making organic chemistry less of a jungle and more a rational science.
Michael Faraday (1791-1867). Faraday's formal education ended with reading and writing, but his
first job, apprentice bookbinder, gave him access to books from which he avidly learned. In 1813 Faraday
became the protege of Sir Humphrey Davy at the Royal Institution, where he spent the rest of his life,
becoming Fullerian Professor in 1833 with a pension of £300 a year for life. Faraday was a prolific
scientist. He carried out pioneering research into the nature of electricity and magnetism, as well as into
electrochemistry and organic chemistry – despite a distrust of mathematics (not one of his papers uses
calculus!). As Professor at the Royal Institution and successor to Davy, Faraday made public lectures,
which were extremely well received. Every Christmas Faraday made special lectures for children, and one
series, The Chemical History of a Candle, has become a classic. A modest man, Faraday declined almost
all the honors offered to him, including the Presidency of the Royal Society and a knighthood. He was
buried in a simple ceremony attended by a few family members and friends with only a simple gravestone
to mark his final resting place.
Eilhardt Mitscherlich (1794-1863). Mitscherlich began his education at the University of
Heidelberg as a student in philology. He had hoped to be appointed as a diplomat to Persia, but when the
fall of Napoleon Bonaparte ended this possibility he returned to his studies as a medical student at the
University of Göttingen. In 1818 he worked in a botanical laboratory, where he analyzed phosphates and
arsenates and developed a theory of isomorphism. In 1819, Berzelius recommended him to succeed
Klaproth at Berlin; after spending two years in Berzelius' laboratories, he did. Here he continued his work
with crystal forms, and he began work in vapor density that led to the experimental confirmation of GayLussac's Law. In 1830 he published a textbook of chemistry. Mitscherlich developed heart disease in
1861, but continued to work until 1862, when his health finally forced him to retire.
Solving the structure of benzene occupied the finest minds of nineteenth-century organic
chemistry. The first to propose the correct cyclic structure for benzene was August Kekulé, who
proposed the structure which we now routinely use to represent the molecule in 1865. Kekulé's
claim is rendered the more romantic by the story which Kekulé himself propagated about his
theory, as told by his eulogist, Professor R. Japp during the Kekulé Memorial Lecture of the
Chemical Society of London in 1898:
According to his own version, the idea came to him during a dream; "I was sitting, writing at my textbook; but the work did not progress, my thoughts were elsewhere. I turned my chair to the fire and dozed.
Again the atoms were gambolling before my eyes. This time the smaller groups kept modestly in the
background. My mental eye, rendered more acute by repeated visions of the kind, could now distinguish
larger structures, of manifold conformation: long rows, sometimes more closely fitted together; all twining
and twisting in snake-like motion. But look! What was that? One of the snakes had seized hold of its
own tail, and the form whirled mockingly before my eyes. As if by a flash of lightning I awoke; and this
709
AROMATIC COMPOUNDS I
Chapter 19 710
time also I spent the rest of the night in working out the consequences of this hypothesis.
"Let us learn to dream, gentlemen," adds Kekulé, "then perhaps we shall find the truth...but let us
beware of publishing our dreams before they have been put to the proof by the waking understanding."
H
H
H
Kekule
1865
H
H
H
Whether or not the Kekulé dream story is fact or apocryphal romanticism is still the topic of
hot – even vitriolic – debate (some versions of the story have him daydreaming while riding a
London bus), and the truth will probably never be known. In the 1990's – nearly a century after
Kekulé's death – it even resulted in a law suit against proponents of the daydream theory. Still,
Kekulé's dream is now firmly entrenched as part of the folklore of organic chemistry. More
importantly, Kekulé's 1865 paper supplied the first widely-disseminated structure for benzene –
dreamt up or not – that provided a rational basis for discussion of its chemistry.
Immediately, chemists recognized that there were problems fitting the known chemistry of
benzene to the Kekulé structure because of the double bonds. Based on the Kekulé structure,
benzene should react as a highly unsaturated compound. It doesn't. Furthermore, the Kekulé
structure predicts that there should be two ortho isomers of dibromobenzene – one where both
bromine atoms are on the same double bond and one where they are on different double bonds;
only one ortho isomer exists.
Br
Br
Br
Br
Br
Br
Br
ortho
Br
ortho
meta
para
The attempts to resolve these inconsistencies between the structure and the chemistry of the
benzene molecule led to many benzene structures being proposed within five years of Kekulé's
paper, and new structures continued to be proposed until the end of the nineteenth century.
Some of the structures are given below.
H
H
H
H
Claus 1867
H
H
H
H
H
H
H
H
[Dewar 1867]
Städeler 1868
Wichelhaus 1869
H
H
H
H
H
H
Ladenburg 1869
H
H
H
H
H
H
H
H
H
L. Meyer 1884
Armstrong-Baeyer
1887-1888
H
H
H
Thiele 1899
At this point, it is worthwhile dispelling some quasi-historical inaccuracies that have crept into
the benzene story over the years. One of these concerns an earlier structure proposed by
Austrian physicist Johann Loschmidt that has been interpreted as being the first cyclic structure
proposed for this molecule. It was not, as Loschmidt himself admitted in his monograph,
Loschmidt's intention to represent a cyclic structure for the benzene molecule because he did not
know the arrangement of the the six carbon atoms of the benzene molecule – he simply used a
larger version of the Dalton symbol for carbon to represent them and he arranged the hydrogens
symmetrically about it. The structure designated as Dewar benzene was not seriously proposed
as a structure for benzene by Sir James Dewar at all, but it was just one of seven possible
structures for benzene which he pointed out could be built with a set of models which he had
developed! It was, instead, proposed by Georg Städeler of the University of Zürich in 1868 and
by Carl Wichelhaus of the University of Berlin in 1869. Likewise, the structure now known as
the Armstrong-Baeyer centric formula was actually first proposed by Lothar Meyer in 1884.
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
Friedrich Karl Johannes Thiele (1865-1918). Thiele was a major figure in nineteenth-century
German organic chemistry. In 1890 he obtained his Ph.D. at the University of Halle under Volhard, and he
remained there to teach organic chemistry and analytical chemistry. In 1893 he moved to Munich, where he
became an assistant professor under Adolf von Baeyer. In 1902 he moved to Strasbourg as Professor of
Chemistry; in 1910 he became Rector of the university. He discovered fulvene, a non-aromatic isomer of
benzene, and his research into nitrogen compounds was essential to the dye, drug and explosive industries.
During World War I, he developed a gas mask against carbon monoxide. His work was a fore-runner of
the electronic mechanisms proposed by Ingold and Robinson. Thiele, who remained a bachelor all his life,
died just seven months before the end of World War I.
Karl Ludwig Claus (1838-1900). Claus entered the University of Marburg as a medical student, but
Kolbe persuaded him to study organic chemistry. After graduate work in Wöhler's laboratories at
Göttingen, he joined the faculty of the University of Freibourg, where he spent the rest of his life. Claus
was one of the first to recognize the importance of structure in organic chemistry, although (surprisingly)
he did not accept van't Hoff's theory of stereochemistry, believing it to be too theoretical. He studied
alkaloids and compounds of naphthalene, anthracene, phenanthrene and quinoline. His structure for
benzene differed from those of Kekulé and Dewar in not requiring any double bonds – a situation more in
accord with the observed chemical properties of benzene.
Sir James Dewar (1842-1923). Dewar, who held chairs in both physics and chemistry, was born in
Scotland, and educated at the University of Edinburgh under Lord Playfair, and at the University of Ghent,
under Kekulé. Dewar's lasting fame is in physics, where he first devised the methods for the liquefaction
of what were called the "permanent gases" (the gases of air), first obtained oxygen in the solid state, and
first obtained liquid hydrogen. His attempt to liquefy helium was foiled because the helium he used was
contaminated with argon, which froze in the lines. His name is preserved in the vacuum flasks now
routinely used to hold cryogenic liquids – Dewar flasks.
Georg Andreas Karl Städeler (1821-1871). Städeler was born in Hannover and educated at the
University of Göttingen, where he took his Ph.D. in 1845 under Wöhler. Following his graduation, he
took a faculty position at Göttingen, eventually rising to the rank of Extraordinary Professor of Chemistry
before moving to the University of Zürich in 1853 as Professor of Chemistry. Städeler worked in both
organic chemistry and inorganic analysis. In 1870 his health forced him to resign his position at Zürich.
He returned to Hannover, where he set up a private laboratory. Less than two years later he died of heart
disease at the age of 49.
Albert Ladenburg (1842-1911). Ladenburg took his Ph.D. in 1863 under Bunsen at Heidelberg,
where he began his life-long friendship with Erlenmeyer. During 1865 he worked with Kekulé in Ghent,
and with Wurtz and Friedel in Paris. His independent career began in Heidelberg in 1868; he moved to the
University of Kiel in 1872 and to Breslau in 1889. Ladenburg was the first to synthesize an alkaloid
(coniine), to resolve a racemic amine, and to determine the molecular formula of ozone. His careful
research on the substitutions of benzene did much to undermine the validity of the structure which he had
himself proposed. Ladenburg received many honors during his lifetime, including the Davy medal of the
Royal Society.
Carl Hermann Wichelhaus (1842-1921). Wichelhaus was born in Elberfeld (near Cologne) and
studied at Bonn, Göttingen, Ghent, and London. He obtained his Ph.D. from the University of Heidelberg
in 1863 and was appointed to the faculty of the University of Berlin in 1867. In 1871 he became Professor
of Chemical Technology at the University of Berlin, a post he held until his retirement to Heidelberg in
1916. During this time he formed the first Technological Institute at the University, and was its director;
from 1877-1880 he was also Director of the Patent Office. Wichelhaus' research was mainly concerned
with the chemistry of aromatic compounds, and he was a major champion of the benzene structure now
known as Dewar benzene.
Henry Edward Armstrong (1848-1937). Armstrong was born in a London suburb, and was
educated at the Royal College of Chemistry under Hofmann and Sir Edward Frankland. He graduated in
1867 and took his Ph.D. under Hermann Kolbe in 1869. During his subsequent academic career he
became a Fellow of the Royal Society and a major force in the Chemical Society of London. His research
covered much of modern chemistry, including naphthalene chemistry, and solvent effects in chemistry. He
criticized the van't Hoff, Ostwald and Arrhenius model of ionization of solutes in aqueous solution for
omitting the role of solvent: in this, as well as his centric formula for benzene, he anticipated to some degree
the modern views. Personally, Armstrong was much like his Ph.D. mentor, Kolbe – irascible and
dogmatic; like Kolbe he was often given to expressing his displeasure in vitriolic language (for example, he
never forgot – nor forgave – being corrected for using a split infinitive in a letter to the Times).
Except for the Ladenburg formula, all the formulas proposed retain the original structural
feature of the Kekulé formula: the planar six-membered ring of carbon atoms with a hydrogen
atom at each vertex. The problem to be resolved, of course, was to explain the lack of reactivity
of the benzene molecule, and the number of isomeric substituted benzenes that exist.
The Claus, Ladenburg and Armstrong-Baeyer formulas for benzene sought to address the
problem of the lack of typical alkene reactivity by assigning structures devoid of any double
bonds. In the Claus formula, all the "diagonal" bonds are long bonds; in the Ladenburg formula,
the molecule is not planar, but is prismatic; in the Armstrong-Baeyer formula, the fourth valence
of each carbon atom is directed towards the center of the ring in a rather undefined way. Thiele
modified the Kekulé structure by adding the "partial valencies" between the double bonds: his
own research with conjugated dienes had shown him that these compounds often react by 1,4-
711
AROMATIC COMPOUNDS I
Chapter 19 712
rather than 1,2-addition, and he proposed the partial valence concept to rationalize this reactivity:
by being cyclic, benzene should be unusually unreactive.
Of course, someone with Kekulé's ego could not remain passive in the face of the objections
to his structure. In order to answer them, Kekulé proposed that the double bonds were in a
continual state of flux, an idea similar to the modern concept of resonance (except that Kekulé
believed that what we now would call canonical forms actually represented real compounds that
were in rapid equilibrium with each other). Städeler's modification of Kekulé's structure is really
a compromise between the original Kekulé structure and the Claus formula, but he also espoused
Kekulé's idea of constant flux to avoid the objections raised by the presence of the two double
bonds in his structure. Thanks to the resonance theory developed by Linus Pauling, today we
represent the benzene molecule as the resonance hybrid of the two canonical forms shown;
frequently, the π bonds of the ring are represented by a circle, as shown in the structure given on
the right.
There are twelve possible isomeric substitution patterns of benzene by one or more identical
substituents. As the number of chemically different substituents on a ring increases, the number
of possible isomers also increases. The bromination of o-dichlorobenzene gives only two
compounds: 1,2-dichloro-3-bromobenzene and 1,2-dichloro-4-bromobenzene. The bromination
of o-chlorotoluene, on the other hand, gives four compounds: 1-methyl-2-chloro-3bromobenzene, 1-methyl-2-chloro-4-bromobenzene, 1-chloro-2-methyl-4-bromo-benzene, and 1chloro-2-methyl-3-bromobenzene. It was by studies of this type that Wilhelm (Gugliemo) Körner
was able to establish that all six carbons of the benzene ring are equivalent, as well as being able
to identify the substitution patterns in benzene derivatives.
Cl
Cl
Cl
Cl
Cl
Br
Br
CH3
CH3
Cl
+
Cl
Br
+
Br
Cl
CH3
CH3
CH3
+
Cl
Br
Cl
Cl
+
Br
Problem 19.5. How many monobromobenzenes would be expected for (i) Kekulé's
formula; (ii) Claus' formula; (iii) von Baeyer's formula; (iv) Dewar's (Städeler's) formula;
and (v) Ladenburg's formula for benzene if the bonds do not move? How many
dibromobenzenes? How many tribromobenzenes?
Problem 19.6. How many isomers of dibromochlorobenzene could possibly be formed
from each of the isomeric dibromobenzenes?
Problem 19.7. How many isomers of chlorobromofluorobenzene are possible? How
many of these could be formed from each of the three isomers of
bromofluorobenzene?
Problem 19.8. An isomer of xylene is treated with nitric acid under conditions that give
the nitroxylene with one nitro group. Separation of the reaction mixture gives three
different nitroxylenes. What was the structure of the original xylene?
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
Gugliemo (Wilhelm) Körner (1839-1925). Körner was educated at the University of Giessen,
where he took his Ph.D. under Heinrich Will in 1864. He remained at Giessen under Kekulé, and moved
with him to Ghent, where he stayed until 1867, except for a six-month sojourn in London. When Kekulé
left Ghent for Bonn, Körner moved to Palermo instead for reasons of health. In Palermo, he entered
Cannizzaro's laboratories; it was here that he developed his method for determining the substitution patterns
of polysubstituted benzenes that unequivocally established the equivalency of all six hydrogen atoms of
benzene. In 1870 the "Scuola Superiore di Agricoltura" was founded at Milan, and Körner became the first
Professor of Organic Chemistry. Although the existing university statutes mandated retirement at age 75,
the staff of the University forced the administration to retain him as professor until age 83, when failing
health forced him to give up active teaching. During his career, Körner received many honors, including the
Davy medal of the Royal Society, and Chevalier of the Order of Savoy.
Aromatic resonance stabilization energy
Now the question which we must answer is, "Just how much stabilization does the benzene
molecule gain from being aromatic?" The resonance stabilization energy of the benzene
molecule cannot be measured directly because it involves the preparation and isolation of the
theoretical molecule cyclohexatriene (in which all of the double bonds are independent).
However, the resonance stabilization energy may be calculated by using experimentally-measured
heats of hydrogenation and heats of combustion of cyclohexene and the cyclohexadienes to
estimate the heat of formation (or the heat of combustion or the heat of hydrogenation) for
cyclohexatriene and then determining the difference between that value and the corresponding
value for benzene. The answer varies a little, depending on the experimental data used and the
theoretical assumptions made about the hypothetical 1,3,5-cyclohexatriene molecule. Most values
are in the range 34-36 kcal/mole.
cyclohexene:
C6H10 + H2 → C6H12
extrapolate to 1,3,5-cyclohexatriene:
ΔH = -119.5 kJ mol-1
ΔH = -358.5 kJ mol-1
benzene:
C6H6 + 3 H2 → C6H12
ΔH = -208.5 kJ mol-1
Resonance stabilization energy of benzene:
ΔH = -150.0 kJ mol-1
[ = -358.5 - (-208.5) kJ mol-1 or -35.8 kcal mol-1]
If we assume that conjugation must be taken into account,
1,3-cyclohexadiene:
C6H8 + 2 H2 → C6H12
ΔH = -231.8 kJ mol-1
difference from cyclohexene:
ΔH = -112.3 kJ mol-1
difference due to double bond in conjugation:
ΔH = -7.2 kJ mol-1
extrapolate to 1,3,5-cyclohexatriene:
ΔH = -336.9 kJ mol-1
(requires one more double bond, and all three double bonds conjugated)
Resonance stabilization energy of benzene:
ΔH = -128.4 kJ mol-1
-1
-1
[ =-336.9 - (-208.5) kJ mol or -30.7 kcal mol ].
The heat of hydrogenation of cyclohexene to cyclohexane has been measured as anywhere
between -98 kJ mol-1 and -119.5 kJ mol-1. The measured heat of hydrogenation of benzene to
cyclohexane is -208.1 kJ mol-1. If we assume that the three double bonds do not interact in the
hypothetical cyclohexatriene, the heat of hydrogenation of the molecule should be three times the
value for cyclohexene – close to 360 kJ mol-1. Instead, it is close to -210. The difference, 150 kJ
mol-1 (36 kcal mol-1), represents the difference in energy between the aromatic, delocalized
benzene molecule with six equivalent carbon-carbon bonds, and the non-aromatic, localized
cyclohexatriene molecule with three carbon-carbon single bonds and three carbon-carbon double
bonds – the aromatic resonance stabilization energy. Even if we assume that one must allow
for the effects of conjugation in the cyclohexatriene, the overall resonance stabilization energy still
remains 128 kJ mol-1 (31 kcal mol-1).
713
AROMATIC COMPOUNDS I
Chapter 19 714
The polycyclic aromatic hydrocarbons are also stabilized by aromatic resonance stabilization
energy, although the stabilization per ring is less than that of benzene. As one might predict on
the basis of simple resonance theory resonance stabilization generally increases as the number of
equivalent canonical forms that one can write for the structure increases. The heterocyclic
aromatic compounds are also stabilized by resonance: pyridine has approximately the same
resonance energy as benzene, while the five-membered aromatic heterocycles tend to have lower
stabilization energies (e.g. the stabilization energy of furan is only about 14 kcal mol-1).
19.3 AROMATICITY AND THE MOLECULAR ORBITAL MODEL OF
BENZENE: HÜCKEL AROMATICITY.
By the end of the nineteenth century, the planar hexagon formula for benzene had become
firmly established, and the term aromatic had come to represent a compound derived from
benzene, or an unsaturated compound whose reactivity was similar to that of benzene.
Unanswered by this definition, of course, is the central question – "Why?" The search for an
answer to this question is as intriguing a story as as any in organic chemistry.
As early as 1887, English chemist H.E. Armstrong had suggested that that aromatic character
was linked to a sextet of "free" valencies; it was these "free valencies" that are indicated by the
short bonds directed towards the center of the ring in the Armstrong-Baeyer structure for
benzene. In more modern terms, the Armstrong sextet of free valencies has become a sextet of
π electrons. Although the Armstrong theory was attractive in its relative simplicity, it did not
satisfy most organic chemists, and it was left to the German physicist, Erich Hückel to make the
theoretical breakthrough that rationalized aromaticity and allowed chemists to predict the
structures of new compounds which should be aromatic.
In 1931, Hückel carried out a series of molecular orbital calculations that showed that cyclic,
planar, conjugated polyenes containing (4n+2) π electrons, where n is an integer (0, 1, 2, 3, ...)
should be unusually stable; these compounds are aromatic. The same calculations showed that
cyclic, planar, conjugated compounds containing 4n π electrons should be unusually unstable;
these compounds are antiaromatic. From Hückel's work, a set of four basic structural and
electronic requirements for aromaticity emerged:
1. All aromatic compounds are planar.
2. All aromatic compounds are cyclic.
3. All aromatic compounds have a linearly conjugated, delocalized π bond system.
4. All aromatic compounds have 4n+2 π electrons delocalized in the π bonding
system, where n is an integer. (Compounds with 4n π electrons are antiaromatic.)
Since all known aromatic compounds meet every one of these structural requirements,
determining whether or not a compound is aromatic simply becomes a problem of determining
whether a compound possesses all four of these characteristics. Let us now use these four
characteristics structural characteristics of aromaticity to determine whether or not the following
four example hydrocarbons are aromatic, antiaromatic, or non-aromatic.
CH2
fulvene
azulene
pentalene
18-annulene (cyclooctadeca1,3,5,7,9,11,13,15,17-nonaene)
cyclododeca-1,5,9triene-3,7,11-triyne
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
Hydrocarbon example 1. Fulvene, C6H6.
Fulvene is an isomer of benzene first prepared by Thiele in his quest for new aromatic
compounds. In order to be aromatic, a molecule must first be planar, and possess a cyclic,
conjugated π bond system. In the fulvene molecule, the carbon atoms are all sp2 hybridized, so
that the molecule is planar. The molecule consists of strictly alternating single and double bonds,
so it is conjugated, but the molecule does not have the linear conjugation required for aromaticity
– it is cross-conjugated instead. Consequently, we expect that fulvene will be neither aromatic
nor antiaromatic; it is non-aromatic.
Hydrocarbon example 2. Azulene, C10H8.
Most fresh motor oil has a blue-green sheen to it. This color is due to the presence of small
quantities of azulene, a hydrocarbon which was named for its blue ("azure") color. In the azulene
molecule, all ten carbon atoms are sp2 hybridized, so that the molecule is planar. The next
question requires that we determine if the π bonding system is conjugated and cyclic, a question
complicated by the fact that there are two rings fused together through a common side in the
azulene molecule. In a fused-ring system such as azulene, one writes the structure so that the
conjugated π system – if one is present – is around the perimeter of the molecule. If one can
write the full conjugated system around the perimeter, the system is cyclic; if not, it is not. When
the azulene molecule is written in this way, one can write the conjugated π electron system so
that all five of the π bonds – all ten of the π electrons – are involved in a linearly conjugated
conjugated system. Therefore, the azulene molecule satisfies the structural requirements for
aromaticity. However, in order to be aromatic, the planar, cyclic, conjugated π electron system
of the molecule must contain 4n+2 π electrons. If we solve the equation 4n+2=10, we find that n
is an integer (2), which means that azulene is aromatic.
Hydrocarbon example 3. Pentalene, C8H6.
Structurally, the pentalene molecule closely resembles the azulene molecule: all eight carbon
atoms are sp2 hybridized, so the molecule is planar; the molecule has two fused rings; and all four
of the π bonds (all eight of the π electrons) can be involved in the conjugated system when it is
written around the perimeter. However, there is a major difference between pentalene and
azulene when one checks the molecule to see if it satisfies the electronic requirements for
aromaticity. If we solve the equation 4n+2=8, we find than n is not an integer (it is actually 1.5);
pentalene, we predict, will not be aromatic. In fact, it is the equation 4n=8 which has an integer
as the solution, so that Hückel's theory predicts that it should be antiaromatic, and unusually
unstable. Again, the theory predicts what is observed experimentally.
Hydrocarbon example 4. [18]Annulene, C18H18.
This molecule is a typical representative of a class of compounds in which there is a single
large ring with alternating π and σ bonds. These compounds, which are known as annulenes
(Latin annulus, a ring) have names that indicate the ring size; usually they have only single and
double bonds in the ring, as in [18]annulene, but they may also have triple bonds in the ring, in
which case they are usually referred to as dehydroannulenes. The [18]annulene molecule
satisfies all the structural requirements for aromaticity: it is planar and conjugated, and the
conjugated π electron system is cyclic. When one solves the equation 4n+2=18, one obtains an
integer (4) for n, so one predicts that 18-annulene should be aromatic. In its chemistry,
[18]annulene is not as unreactive as benzene, but it still exhibits the same tendency to react with
electrophiles to give substitution products that characterizes aromatic compounds, and it exhibits
certain spectroscopic characteristics associated with aromaticity – [18]annulene is aromatic.
715
AROMATIC COMPOUNDS I
Chapter 19 716
Hydrocarbon example 5. Cyclododeca-1,5,9-trien-3,7,11-triyne.
The analysis for dehydroannulenes (such as cyclododeca-1,5,9-trien-3,7,11-triyne) is essentially
the same as for the corresponding annulenes. The two π bonds of a triple bond are orthogonal
to each other, so each triple bond can contribute only two π electrons to the conjugated system.
Thus, there are twelve π electrons in the planar, cyclic, conjugated π bond system of this
dehydroannulene. The solution to the equation 4n+2=12 is not an integer, but the solution to the
equation 4n=12 is; this dehydroannulene is, therefore, antiaromatic.
The presence of heteroatoms introduces another variable into the question of aromaticity,
especially if those heteroatoms bear lone pairs of electrons.
O
N H
N
pyridine
O
pyrrole
1,4-dioxin
Heterocyclic example 1. Pyridine, C5H5N.
In the pyridine molecule, the nitrogen atom must be sp2 hybridized because it is involved in
one carbon-nitrogen π bond. This means that every atom in the six-membered ring is sp2
hybridized, so that the π orbital system is cyclic. If all six atoms in the ring are sp2 hybridized,
the ring must also be planar. The single and double bonds alternate around the ring, and the
pyridine molecule is, therefore, conjugated. Therefore, the pyridine molecule satisfies the
structural requirements for aromaticity. However, in order to be aromatic, the planar, cyclic,
conjugated π electron system of the molecule must contain 4n+2 π electrons. In the pyridine
molecule, there are three π bonds, so that there are six π electrons in the molecule. If we solve
the equation 4n+2=6, we find that n is an integer (1), which means that pyridine also satisfies the
electronic requirements for aromaticity. We therefore predict that pyridine will be aromatic.
And it is.
Heterocyclic example 2. Pyrrole, C4H5N.
In the pyrrole molecule, the nitrogen is not involved in a double bond, so on the basis of our
discussions in Chapter 2 we would predict that the nitrogen will be sp3 hybridized. However, if
the nitrogen is sp3 hybridized, the π electron system of the molecule could not be cyclic, so that
the molecule would be non-aromatic. However, what happens if the nitrogen atom is sp2
hybridized, with the lone pair now in a 2p orbital instead of a hybrid orbital? Now every atom in
the ring would be sp2 hybridized, so the conjugated π electron system would be cyclic and
planar. It will contain six π electrons (four from the carbon atoms and two from the
heteroatom), and it will therefore satisfy the (4n+2) π electron requirement: pyrrole is aromatic.
Heterocyclic example 3. 1,4-Dioxin, C4H4O2.
This simple molecule is the basic ring system from which the halogenated dibenzodioxins (the
"dioxins of the popular press) derive their names. Clearly, if either of the oxygen atoms is sp3
hybridized, this molecule is non-aromatic. But what if both are sp2 hybridized? Now, each
oxygen atom will have one lone pair is a 2p orbital, and one lone pair in an sp2 hybrid orbital.
With all six atoms sp2 hybridized, the molecule will be planar, so that the conjugated π electron
system will be planar and cyclic. However, the molecule will also possess 8 π electrons, which
satisfies not the (4n+2) π electron requirement for aromaticity, but the (4n) π electron
requirement for antiaromaticity. If the molecule exists in the completely delocalized, planar form,
we predict that it will be antiaromatic.
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
Problem 19.9. Which of the following hydrocarbons will be aromatic, and which will be
antiaromatic?
(a)
(b)
(c)
(d)
Problem 19.10. Predict whether isothiazole (structure below) will be aromatic.
N
S
Problem 19.11. Cyclobutadiene, which is predicted by the analysis above to be
antiaromatic, has been isolated in a solid argon matrix at very low temperature. The
spectroscopic analysis of this molecule shows that it is not square at all, but that it is
rectangular. What inferences do you draw from this ?
Erich Armand Arthur Joseph Hückel (1896-1980). Hückel was born in Berlin-Charlottenburg,
the younger brother of Walter Hückel, who became an eminent organic chemist. Hückel studied physics
and natural science at the University of Göttingen, obtaining his Ph.D. in 1921 under physical chemist
Peter Debye in 1921. Unfit for military duty, he served during World War I as a laboratory assistant in the
model experimental station for aerodynamics. Immediately after his graduation, Hückel studied with
mathematician David Hilbert and with Max Born, before moving to Zürich in 1922 to work again with
Debye. In 1930 he was appointed to the faculty in chemical physics at the Technische Hochschule in
Stuttgart, and in 1937 he moved to the University of Marburg, where he spent the remainder of his life as
professor of theoretical physics. Although he was a physicist, Hückel is best remembered for two seminal
contributions to chemistry: the Debye-Hückel theory of strong electrolytes and Hückel molecular orbital
theory.
Molecular orbitals in benzene and aromatic compounds
Every π orbital of an aromatic compound is completely delocalized over the entire ring
system. Unlike the orbitals of conjugated acyclic systems, where each orbital is at a different
energy level, cyclic, delocalized π orbitals occur as a single lowest-energy π orbital, with all
higher-energy orbitals occurring as degenerate pairs. The six π orbitals of benzene are shown
schematically in Figure 19.1, where the ring is viewed from the top.
One can predict the relative energies of cyclic delocalized π orbitals by using the following
simple device. Draw the polygon representation of the molecule and orient it so that one vertex
of the π orbital system points directly towards the bottom of the page. In this orientation all the
vertices of the polygon except the bottom one (and, in even-sided polygons, the top one) are now
paired – just like the energies of the π orbitals of the cyclic conjugated system. Now fill these
orbitals with electrons according to the Aufbau principle: when the π electron system has (4n+2)
π electrons, all the electrons are paired, but when the π electron system has (4n) π electrons, the
system always has two unpaired electrons (Figure 19.2).
717
AROMATIC COMPOUNDS I
Chapter 19 718
ψ6
3 nodal planes
perpendicular to
plane of ring
ψ4,ψ5
2 nodal planes
perpendicular to
plane of ring
ψ2,ψ3
1 nodal plane
perpendicular to
plane of ring
ψ1
0 nodal planes
perpendicular to
plane of ring
Figure 19.1 The π molecular orbitals of the benzene molecule viewed from above the aromatic ring. Four
of the orbitals actually occur as two degenerate pairs of orbitals which differ only in the orientation of the nodal
planes perpendicular to the plane of the ring.
Figure 19.2 The relative energies of the π molecular orbitals of a cyclic, delocalized π orbital system may
be approximated by drawing a polygon with the number of sides equal to the number of p orbitals involved vertex
down. The dotted lines indicate the non-bonding energy levels.
Sample Problem 19.2. Draw the structure and the molecular orbital energy diagram for
(a) (CH)5+ , (b) (CH)5•, and (c) (CH)5–, and predict whether each will be aromatic, nonaromatic or antiaromatic. Give reasons for your answer.
Answers:
•
cation
anti-aromatic
radical
non-aromatic
anion
aromatic
The cation has only 4 π electrons (a 4n system): if it is delocalized it contains two
unpaired π electrons and is anti-aromatic. The free radical has 5 π electrons (neither 4n
nro 4n+2) – it is non-aromatic. The anion has 6 π electrons (a 4n+2 system): if it is
delocalized all six π electrons are paired and the system is aromatic.
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
Problem 19.12. Draw the structure and the molecular orbital energy diagram for each of
the following species, and predict whether each will be aromatic, non-aromatic, or antiaromatic. Give reasons for your answer.
(a) (CH)82–.
19.4
(b) (CH)7+ .
(c) (CH)42 +.
(d) (CH)9–.
(e) (CH)3•.
REACTIVITY OF AROMATIC COMPOUNDS: A N OVERVIEW
ELECTROPHILIC AROMATIC SUBSTITUTION
OF
Benzene does not form addition compounds with electrophiles except under vigorous reaction
conditions or with highly reactive reagents such as ozone. When a benzene ring carries an alkyl
substituent (a side-chain), most of the chemistry occurs in the side-chain – the ring survives the
reaction intact. Some idea of the lack of reactivity of benzene towards electrophilic addition may
be obtained by a comparison of the reactions of benzene and cyclohexene with some common
electrophiles that react quite readily with alkenes (Figure 19.3). With cyclohexene, the addition of
these reagents proceeds under mild reaction conditions to give the addition product as the major
(or sole) product of the reaction. With benzene the reactions fail.
N/R
N/R
N/R
Br2/CCl4
Br2/CCl4
Br
Br
OH
KMnO4/KOH/H2O
KMnO4/KOH/H2O
KOCMe3/CHCl3
KOCMe3/CHCl3
OH
Cl
1) BH3•THF
OH
Cl
N/R
N/R
1) BH3•THF
2) H2O2/OH–/H2O
m-CPBA/CH2Cl2
2) H2O2/OH–/H2O
m-CPBA/CH2Cl2
O
Figure 19.3 A comparison or the reactivity of benzene (left) and cyclohexene (right) with representative
electrophilic reagents shows just how unreactive the benzene ring system is towards most electrophiles.
However, the reactions in Figure 19.3 should not be taken to indicate that the benzene
nucleus is chemically inert. It is not (how could it be, with six π electrons?). However, when
benzene reacts with electrophilic reagents the compound obtained is the product of substitution
rather than addition. This electrophilic aromatic substitution, where a hydrogen atom is
replaced by an electrophilic reagent (Figure 19.4), is characteristic of aromatic compounds. Note
how most of the electrophilic substitution reactions of benzene require the presence of a
powerful electrophile such as aluminum chloride to catalyze the reaction.
719
AROMATIC COMPOUNDS I
Chapter 19 720
Br2/FeBr3
H2SO4/Δ
sulfonation
SO3H
Br
bromination
HNO3/H2SO4
NO2
nitration
(CH3)3CCl/AlCl3
alkylation
O
CH3COCl/AlCl3
acylation
Figure 19.4 Representative electrophilic substitution reactions of benzene; note how strong electrophiles
(e.g. FeBr3, AlCl3) are frequently used to catalyze the reactions.
Electrophilic aromatic substitution in benzene
Electrophilic aromatic substitution proceeds by a two-step mechanism involving initial addition
of the electrophile to the aromatic π electron system to give a resonance-stabilized benzenonium
ion intermediate, followed by loss of the hydrogen atom as a proton to re-establish the
aromaticity in the π electron system (Figure 19.5).
E
H E
H E
addition
E
H E
benzenonium ion
elimination
Figure 19.5. The currently-accepted mechanism for electrophilic aromatic substitution involves two steps:
first the electrophile adds to the π system of the ring to give a resonance-stabilized benzenonium ion (addition),
then a proton is lost to give the substitution product (elimination).
Thus, although the net result of the two steps is substitution, it occurs by a route that is more
consistent with what we already know about carbon-carbon π bonds – the first step of the
reaction is an exact parallel of electrophilic addition to an alkene, while the second step is exactly
the same as the second step of the E1 elimination reaction which we studied back in Chapter 8.
E
δ+
H
‡
E
H δ+
‡
δ+
δ+
H
H E
E
benzenonium ion
Extent of Reaction
Figure 19.6 The energy profile of a typical electrophilic aromatic substitution. The fist step involves loss of
the aromaticity in the ring, and is the rate determining step of the reaction.
The energy profile of a typical electrophilic aromatic substitution reaction is shown in Figure
19.6. In the first step of the reaction the aromaticity of the ring is lost, and the first step is
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
therefore is very endothermic. In fact, it is always the rate-determining step. Because it is a
strongly endothermic reaction, the first step if the substitution reaction also requires a very strong
electrophile to proceed. For example, bromine, which is a strong enough electrophile to add to
the HOMO of an alkene, is not strong enough to add to the HOMO of benzene.
Substitution vs. addition
Let us now answer the question, "Why substitution instead of addition?" We can best answer
this question by contrasting the behavior of cyclohexene and benzene towards bromine as a
typical electrophile. As you will recall, the addition of bromine to cyclohexene proceeds in two
steps. In the first step of the reaction, the alkene π electrons displace a bromide ion from the
bromine molecule to form the three-membered, cyclic bromonium ion. The bromonium ion then
reacts with the bromide anion in an SN2 process to give the overall anti addition product.
Br
Br Br
(±)
Br
Br
••
Br
The energy changes associated with this addition reaction are summarized in Table 19.2.
Overall, the reaction involves the rupture of a C–C π bond (average bond energy 64 kcal mol-1
[268 kJ mol-1]) and a Br–Br σ bond (bond energy 46 kcal mol-1 [192 kJ mol-1]), and their
replacement by two C–Br σ bonds (average bond energy 66 kcal mol-1 [276 kJ mol-1]). Based
on the average bond energies of the bonds involved, one may calculate that this process is an
energetically favorable process with an approximate ΔH of approximately -22 kcal mol-1 [-92 kJ
mol-1].
Table 19.2 Energy Changes During Addition of Bromine to Cyclohexene
Average Bond Energy
kcal mol-1
kJ mol-1
Bonds Broken
C–C π
Br–Br σ
64
46
268
192
C–Br σ
66
–22
276
–92
Bonds formed
Overall energy change
Were it not for the aromatic resonance stabilization energy of the ring, one would expect the
electrophilic addition reaction of benzene to be energetically favorable by about the same amount
(approximately 22 kcal mol-1). However, when one takes into account the fact that the addition
reaction must result in the loss of the aromaticity of the ring, the reaction now becomes
endothermic (ΔH ≈ +14 kcal mol-1), and the electrophilic addition reaction becomes very
unfavorable under normal reaction conditions. In contrast to this, the substitution reaction
involves the overall rupture of a C–H σ bond and a Br–Br σ bond and their replacement by a
C–Br σ bond and a H–Br σ bond. Using average bond energies in much the same way as in
Table 19.2, this process is energetically favorable by approximately 8 kcal mol-1.
721
AROMATIC COMPOUNDS I
Chapter 19 722
Br
H
ΔH ≈ +14 kcal mol -1
Br
Br
Br Br
Br
••
ΔH ≈ -8 kcal mol -1
Br
Problem 19.13. Using the average bond energies below in kcal mol-1 [kJ mol-1],
construct a table like Table 19.2 to show the calculated ΔH values for the two possible
competing reactions (addition and substitution) between benzene and bromine.
C–C π bond: 64 [268]; C–H σ bond: 99 [414]; H–Br σ bond: 87 [364]; Br–Br σ bond:
46 [192]; resonance stabilization energy: 36 [151].
19.5 ELECTROPHILIC AROMATIC SUBSTITUTION IN BENZENE
Nitration
The reaction between an aromatic compound and a mixture of nitric and sulfuric acids is
known as nitration, and gives the nitro compound as product. The active electrophile in the
nitration reaction is the nitronium ion, NO2+ , which is formed by the reaction between
concentrated nitric and sulfuric acids.
HNO3 + 2H2SO4 → NO2+ + 2HSO4– + H3O+
The nitronium ion is one of the most powerful electrophiles known, and it readily nitrates
benzene at low temperatures.
HNO3/H2SO4
NO2
(85%)
The mechanism of nitration follows the same course as the general mechanism in Figure 19.5.
The initial overlap is between the HOMO of the benzene molecule (either ψ2 or ψ3) and the
LUMO of the nitronium ion (an N–O π* orbital). The frontier orbital overlap is represented
schematically in Figure 19.7. In one way this first step has many of the characteristics of the
nucleophilic addition reactions which we studied in the chapters describing the chemistry of
carbonyl compounds because the N–O π bond is ruptured during the initial electrophilic addition
step of the mechanism.
LUMO (π*)
O N O
O
O
O
N
H
O
N
O
N
O
HOMO (ψ2 )
Figure 19.7. The mechanism and frontier orbital overlap involved in the nitration of benzene by nitronium
ion, NO2 + . Note the similarity of the frontier orbital overlap in this addition reaction to the frontier orbital overlap
for nucleophilic addition to a carbonyl group.
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
Halogenation
As implied in the earlier sections of this chapter, the halogens themselves (fluorine excepted)
are not reactive enough to give a substitution product with benzene. In these cases, the halogen
molecule is converted into a more active electrophile by first complexing it with a strong Lewis
acid such as aluminum chloride or ferric bromide; the Lewis acid may be formed during the
reaction itself:
3Cl2 + 2Al → 2AlCl3
3Br2 + 2Fe → 2FeBr3
Cl2/Al(Hg)
(49%)
Cl
When chlorine is added to a solution of aluminum chloride, the halogen molecule functions as
the Lewis base to form the Lewis acid-Lewis base complex shown below.
Cl
Cl
Cl
Cl
Cl
Al
Cl
Al
Cl
Cl
Cl
Cl
The LUMO involved in the electrophilic addition step of this substitution reaction is the σ*
orbital of the halogen-halogen bond, so that the initial electrophilic addition has some of the
characteristics of the SN2 nucleophilic displacement reaction where the leaving group is the
AlCl4– anion (Figure 19.8).
Cl
Al
Cl
LUMO (σ*)
Cl
Cl
Cl
Cl
H
Cl
Cl
AlCl3
Cl
HOMO (ψ2)
Figure 19.8. The mechanism and frontier orbital overlap of the electrophilic addition step of the
chlorination of benzene. Note the similarity of the orbital overlap to that of the SN2 displacement reaction.
Friedel-Crafts Alkylation
While studying the effects of metallic aluminum on reactions between benzene and alkyl
halides, French chemist Charles Friedel and his student, American James Mason Crafts, observed
that copious quantities of hydrogen chloride were evolved and the benzene was converted to a
mixture of alkylbenzenes after a brief induction period. Later they found that it was aluminum
chloride that was actually the catalyst of the reaction. This reaction is quite general and adaptable
to most alkyl halides that will undergo SN1 or SN2 reactions. It is now known as the FriedelCrafts alkylation, and it is a very important method for the formation of carbon-carbon bonds
between an aromatic ring and an alkyl group. The electrophile in the Friedel-Crafts reaction with
aluminum chloride as the catalyst may be viewed as the alkyl halide-aluminum chloride complex
analogous to the chlorine-aluminum chloride complex shown in Figure 19.8.
723
AROMATIC COMPOUNDS I
Cl
Al
R
Chapter 19 724
LUMO (σ*)
Cl
Cl
Cl
Cl
H
R
R
AlCl3
R
HOMO (ψ2)
Figure 19.9. Friedel-Crafts alkylation proceeds through the Lewis acid–Lewis base complex between an
alkyl halide and aluminum chloride.
When the alkyl halide can undergo substitution by the SN1 mechanism, the carbocation is the
electrophile instead of the alkyl halide–Lewis acid complex.
R
Cl
AlCl3
R
+
AlCl4
Where the carbocation can rearrange to a more stable cation, it does so, and the rearranged
product is formed: Benzene reacts with n-propyl chloride in the presence of aluminum chloride
to give mainly n-propylbenzene at room temperature (where little of the free carbocation is
formed) and mainly isopropylbenzene (cumene) at high temperatures (where the formation of the
free carbocation from the complex is more favored). The reaction between isobutyl chloride and
benzene in the presence of aluminum chloride gives only t-butylbenzene.
CH3CH2CH2Cl
AlCl3/25°C
CH3CH2CH2Cl
AlCl3/Δ
(CH3)2CHCH2Cl
AlCl3
Friedel-Crafts Acylation
The reaction between benzene and an acid chloride in the presence of a Lewis acid produces
an aromatic ketone (Figure 19.10). The mechanism of the reaction involves either a Lewis acid
complex of the acid chloride, or an acylium ion. The reaction, which is known as FriedelCrafts acylation, is even more important than the alkylation reaction because, unlike alkylation,
it gives only the product where one acyl group has been introduced into the ring
(monoacylation). Unlike the alkylation reaction, where the halide may not be aromatic, the acid
chloride used in Friedel-Crafts acylation may be aliphatic or aromatic, as shown by the examples
below.
O
CH3(CH2)2COCl
(51%)
AlCl3
C6H5COCl
AlCl3
O
C
(66%)
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
Lewis acid-Lewis base complex
O
Cl
Cl
R
O
H
C
AlCl3
••
O
O
C Cl
R
AlCl3
acylium ion
R
O
Cl
O
C
C Cl
R
AlCl3
R
AlCl3
R
O
R
O
R
H
Figure 19.10 The Friedel-Crafts acylation of benzene may proceed either through a free acylium ion or
through the Lewis acid complex of the acid chloride. The final product in either case is the aromatic ketone.
The Friedel-Crafts acylation may also be carried out using an acid anhydride in place of the
acid chloride. This variation of the reaction has been especially widely used with cyclic
anhydrides such as succinic anhydride.
O
O
O
O
(94%)
AlCl3
CO2H
Practically any Lewis acid can serve as the catalyst for the Friedel-Crafts reactions, and many
Lewis acids have been used. The most popular have probably been the boron trihalides, the zinc
halides, anhydrous hydrogen fluoride (especially popular for generating carbocations from
alkenes), and the aluminum halides. Polyphosphoric acid (PPA) is often used as a source of H+
in Friedel-Crafts reactions because of the poor nucleophilicity of the polyphosphate anion.
O
CO2H
PPA/Δ
(H+)
(79%)
Charles Friedel (1832-1899). Friedel was born in Strasbourg and graduated from the University
there. He then spent a year working in his father's counting-house before moving to Paris. In 1854 he
entered Wurtz' laboratories, and in 1856 he was appointed conservator of the mineralogical collection of the
School of Mines. After obtaining his Dr. ès-sc. in 1869, he was appointed to a junior faculty position,
becoming Professor of Mineralogy in 1876 and, on Wurtz' death in 1884, succeeding him as Professor of
Organic Chemistry at the Sorbonne. In 1878 he became director of the Paris Academy. In 1892 he acted
as President of the International Congress which systematized organic nomenclature. Friedel's name is
permanently linked with that of his student and collabiorator, J.M. Crafts, with whom he discovered the
reaction which bears their joint names. He also made contributions in inorganic and organosilicon
chemistry, although the importance of his work in silicon chemistry was not recognized until the later work
of Kipping.
James Mason Crafts (1839-1917). Crafts was educated at Harvard University, and immediately
following his graduation he traveled to Europe where he worked with Bunsen for a year before meeting
Friedel at the Sorbonne. Crafts worked with Friedel for the next seven years before returning to the United
States where, in 1867, he became the first Professor of Chemistry at Cornell University. In 1871 he moved
to Massachusetts Institute of Technology as Professor of Chemistry. He remained at MIT until 1874,
when he returned to Paris to carry out full-time research once again in Friedel's laboratories. He spent the
next 17 years working with Friedel, and in 1874 he discovered the reaction which bears their joint names.
Crafts was also intimately involved with much of Friedel's organosilicon chemistry. In 1891 he returned to
the United States for the last time to resume teaching at MIT, serving as President of that institution from
1898 until his retirement in 1900 due to ill health.
725
AROMATIC COMPOUNDS I
Chapter 19 726
Formylation
Above approximately –60°C, formyl chloride decomposes to hydrogen chloride and carbon
monoxide, so one cannot carry out the reaction corresponding to the Friedel-Crafts acylation,
known as formylation, by treating the aromatic compound with formyl chloride and a Lewis
acid. However, the same overall result can be obtained by subjecting the aromatic compound to
a mixture of carbon monoxide and hydrogen chloride in the presence of aluminum chloride, a
reaction known as the Gattermann-Koch reaction, or by treating the aromatic compound with
zinc cyanide and hydrogen chloride, known as the Gattermann aldehyde synthesis. In the
Gattermann reaction, the reactive electrophile may be viewed as the formyl cation, [H–C≡O]+ ; in
the Gattermann-Koch reaction it is the conjugate acid of hydrogen cyanide, [H–C≡N–H]+ . In
the Gattermann reaction, the final step of the reaction is hydrolysis of an iminium ion
intermediate to give the aldehyde.
CO/HCl/AlCl3/CuCl
Me
Me
1) Zn(CN)2/HCl/AlCl3
Me
(78%)
CHO
2) HCl/H2O
Me
CHO
Me
(80%)
Me
Friedrich August Ludwig Gattermann (1860-1920). Gattermann was born in the historic city of
Goslar in Saxony, and educated at the Universities of Leipzig, Heidelberg, Berlin and Göttingen, where he
obtained his Ph.D. in 1885 under Victor Meyer. He then became Meyer's assistant, following him to
Heidelberg in 1889, where Gattermann became Extraordinary Professor. After just over a decade at
Heidelberg, where he was also a member of the Bunsen Institute, Gattermann moved to Freiburg as
Professor of Chemistry and leader of the Chemical Institute. His research work was primarily concerned
with aromatic chemistry, and it is for his developments of useful syntheses of aromatic aldehydes that he is
remembered. Gattermann's family had a history of atherosclerosis, and he died of a heart attack at age 60.
Sulfonation
The reaction between an aromatic compound and concentrated sulfuric acid or sulfur trioxide
gives a sulfonic acid, which may be viewed as a sulfuric acid molecule with one of the hydroxyl
groups replaced by the organic group. The reaction is called sulfonation. Sulfonic acids and their
salts are important industrial intermediates: the sulfonic acids are strong acids like sulfuric acid,
and find widespread use as strong acid catalysts, and their salts are frequently used as detergents
and in dye intermediates.
H2SO4/Δ
SO3H
Reaction synopsis
Nitration
NO2
Reagents:
HNO3/H2SO4; HNO3/(CH3CO)2O (for activated systems).
Sulfonation
SO3H
Reagents:
Halogenation
H2SO4, SO3/H2SO4; pyridine•SO3.
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
X
X = Cl, Br
Reagents:
Cl2/AlCl3; Br2/Fe, Br2/FeBr3; Br2/pyridine.
Friedel-Crafts Alkylation
R
RCl/AlCl3; ROH/PPA/Δ; R2C=CR2/H+.
Reagents:
Electrophile is a Lewis acid-Lewis base complex if the alkyl group is methyl or primary, and the
carbocation if the alkyl group is secondary, tertiary, allyl or benzyl. The reaction does not occur if the
aromatic ring is strongly deactivated (e.g. nitrobenzene). Polyalkylation may be a problem.
Friedel-Crafts Acylation
COR
Reagents: RCOCl/AlCl3; (RCO)2O/AlCl3.
Electrophile is an acylium ion. The reaction does not occur if the aromatic ring is strongly deactivated
(e.g. nitrobenzene).
Formylation
CHO
Reagents:
19.6
HCl/CO/AlCl3 (Gattermann-Koch);
Zn(CN)2/HCl/AlCl3 (Gattermann);
FACTORS AFFECTING ELECTROPHILIC SUBSTITUTION
SUBSTITUTED BENZENES AND HETEROCYCLIC ARENES
IN
Electrophilic aromatic substitution is affected by two factors: the identity of the aromatic
compound and the electrophile being used. The substitution of benzene is the simplest form that
this reaction can take because benzene is a completely symmetrical molecule, and its electronic
character and reactivity reflect this fact. However, when the benzene ring is substituted, the sixfold symmetry of the ring is lost. Moreover, the substituent on the ring has a dramatic effect the
energies of the frontier orbitals because the degeneracy of the π molecular orbitals of the
aromatic ring is lifted. In other words, substituted benzenes do not have degenerate frontier
orbitals (Figure 19.11). Likewise, the presence of the heteroatom in heterocyclic arenes has a
dramatic effect on their reactivity, with five-membered heterocycles generally being more
reactive than benzene towards electrophiles, and six-membered heterocycles being less reactive.
Effects of substituents on electrophilic substitution in benzene.
As we saw in Chapter 2, electron-withdrawing substituents on a π bond tend to lower the
energy of the associated frontier orbitals, while electron-releasing groups tend to raise the
energies of the frontier orbitals. Thus, electron-withdrawing groups tend to lower the energy of
the HOMO and LUMO of the arene: since the arene reacts through its HOMO, lowering the
energy level of the HOMO increases the energy gap between the HOMO of the arene and the
727
AROMATIC COMPOUNDS I
Chapter 19 728
LUMO of the electrophile, making electrophilic aromatic substitution more difficult. Likewise,
electron-donating groups raise the HOMO energy of the arene, thus decreasing the energy gap
between the arene HOMO and the electrophile LUMO; these molecules tends to react much
more rapidly with electrophiles in general, and to be able to react with much weaker
electrophiles.
note degenerate
orbitals
LUMO
LUMO
LUMO energy of benzene
HOMO
LUMO
HOMO
HOMO energy of benzene
HOMO
H
NO2
OCH3
Figure 19.11 The effects of substituents on the energy levels of the π molecular orbitals of benzene.
Electron-withdrawing groups (e.g. the nitro group in nitrobenzene) lower the energy of both frontier orbitals;
electron-releasing groups (e.g. the methoxy group in anisole) raise the energy of both frontier orbitals.
The substitution of benzene itself can give only one product because all six atoms in the ring
are equivalent. However, if the aromatic ring already carries a substituent or if it contains a
heteroatom, it is possible that more than one substitution product might be formed during the
reaction. So just how does a substituent on an aromatic ring or a heteroatom in the ring affect
the substitution of that ring by an electrophile? We find that they affect the reaction in two ways:
they affect the rate of the reaction (i.e. they activate or deactivate the ring towards substitution),
and they affect the ratio of the regioisomers formed in the reaction. Some typical results from
electrophilic aromatic substitutions of monosubstituted benzene derivatives are summarized in
Table 19.3 (the major isomer(s) of the product have been given in boldface type for emphasis).
Table 19.3 Substituent effects on nitration of monosubstituted aromatic compounds
Substituent
NO2
CO2Et
CN
CH3
CMe3
Cl
OH
Relative rate*
6×10-8
0.0037
–
24.5
15.5
0.033
103
% o isomer
6.4
28.3
15
57
12
30
40
% m isomer
93.3
68.4
83
3.2
8.5
0.9
–
% p isomer
0.3
3.3
0.3
40
79
69
60
*relative to benzene = 1.00
There are a couple of conclusions which we can draw from the data in Table 19.3. On the
basis of which isomer is formed in major amounts, which we call the orientation of the reaction,
electrophilic aromatic substitutions fall into two categories – those where the major product is the
meta isomer, with less (often much less) of the ortho and para isomers, and those where the
ortho and para isomers predominate in the product mixture to the near exclusion of the meta
isomer. We therefore classify substituents on an aromatic ring as being either m-directing or
o,p-directing. The second observation that one can make from the data in Table 19.3 is that all
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
m-directing groups deactivate the ring towards electrophilic substitution. Conversely, all
o,p-directing groups (except the halogens) activate the ring towards electrophilic substitution.
The common structural feature of the m-directing groups is their electron-withdrawing nature.
We have already discussed the effects of electron-withdrawing substituents in terms of the
energies of the frontier orbitals of the arene; now let us examine the resonance-based
rationalizations for their effects on reactivity. One can write several canonical forms for these
benzene derivatives where the π electrons are moved from the ring to an electronegative atom,
as shown in Figure 19.12. The net effect is to reduce the electron density on the ring, and to
place increased positive charge on the ortho and para positions of the ring. This slows down the
overall rate of electrophilic attack on the ring, and slows it down most at the ortho and para
positions, favoring m-substitution.
Z
X
Y
Z
X
Y
Z
X
Y
Z
X
Y
Z
Y δ−
X
δ+
δ+
δ+
Z–X=Y: –O–N+ =O, R–C=O, HO–C=O, RO–C=O, H2N–C=O, RNH–C=O, R2N–C=O, Cl–C=O, C≡N,
N≡N +
Figure 19.12 The resonance effects of an electron-withdrawing substituent on benzene are to decrease the
overall electron density of the ring and to accumulate positive charge at the positions ortho and para to the
substituent. These substituents deactivate the ring towards electrophilic aromatic substitution and when
substitution occurs, it occurs preferentially meta to the substituent.
Substituents with lone pairs affect the reactivity of the aromatic ring towards electrophiles in
two ways – by induction, which is the result of substituent electronegativity, and by resonance,
which is a result of the interaction of lone pairs or π orbitals on the substituent with the π orbitals
of the ring. The inductive effect of a substituent is transmitted through the σ bonding system
only. All substituents based on electronegative heteroatoms (e.g. hydroxy groups) are
electron-withdrawing by the inductive effect. The influence of the lone pairs is transmitted
through the π electron system by resonance. All substituents bearing lone pairs of electrons
on the atom directly bonded to the aromatic ring are electron-releasing by resonance.
When one writes the possible canonical forms for these benzene derivatives where the lone pair is
delocalized into the ring, the net effect is to reduce the electron density on the heteroatom and to
increase the electron density at the ortho and para positions of the ring (Figure 19.13). This
should both increase the ease of attack on the ring and favor attack at the ortho and para
positions.
••
X
X
X
X
X
δ+
δ−
δ−
••
δ−
X: OH, OR, OCOR, NH2, NHR, NR2, NHCOR, NRCOR, F, Cl, Br, I, SH, SR
Figure 19.13 The resonance effects of an electron-releasing substituent on benzene are to increase the
overall electron density of the ring and to accumulate negative charge at the positions ortho and para to the
substituent. These substituents usually activate the ring towards electrophilic aromatic substitution and when
substitution occurs, it occurs preferentially ortho and para to the substituent.
The resonance effect of a substituent lone pair is even more influential in the intermediate
benzenonium ion. If we draw the possible canonical forms of the benzenonium ion resulting
from addition of the electrophile para to the substituent and those of the corresponding
benzenonium ion from addition at the m position, a very important difference emerges. In the
729
AROMATIC COMPOUNDS I
Chapter 19 730
ion resulting from para attack, it is possible to draw one canonical form where every nonhydrogen atom has a complete valence-shell octet. Recall from our discussions in Chapter 2
that this is an especially favorable situation, so we predict that this structure will be the major
contributor to the overall resonance hybrid, and that this ion will be the more stable of the two
(Figure 19.14).
•X•
•X•
•X•
X
H E
H E
H E
H E
•X•
addition at p- position
•X•
H E
•X•
H E
H E
addition at m- position
Figure 19.14 The addition of an electrophile para to a substituent carrying a lone pair of electrons allows
the positive charge to be delocalized onto the substituent in such a way that every non-hydrogen atom carries a
complete valence-shell octet of electrons. No similar canonical form for the corresponding meta isomer can be
drawn; all the contributing structures for this ion have at least one electron-deficient atom.
The resonance effect of a lone pair of electrons on the atom bonded directly to the ring
dominates the directing effect of these substituents. All such substituents are o,p-directing.
Except for the halogens, the electron release from these substituents to the ring by resonance is
more effective than electron withdrawal by induction, so that these substituents activate the ring
towards substitution. With the halogens, however, the inductive effect is stronger, and the
halogens deactivate the ring towards electrophilic substitution. The activating or deactivating
propensities of several common substituents are summarized in Table 19.4 in approximately
decreasing order of strength.
Table 19.4 Common Activating and Deactivating Groups
Activating Groups
o,p- Directing
Groups
–O–
–NR2
–OH
–OR
–NR–CO–R
–O–CO–R
–R
m-Directing
Groups
none known
Deactivating Groups
o,p- Directing
Groups
Cl, Br, I
m-Directing
Groups
–NR3+
–NO2
–SO2–R
–C≡N
–CO–R
–CO-OR
–CO–NR2
Sample Problem 19.3. Draw all the canonical forms for the most stable benzenonium ions
formed by the addition of Br+ either ortho or meta to the substituent in each of the
following aromatic compounds. Give reasons for your choice of benzenonium ion, and,
where appropriate, indicate which of the canonical forms will be the major contributor
to the overall resonance hybrid for the benzenonium ion.
(a) benzaldehyde. (b) acetanilide.
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
Answers:
(a) The aldehyde functional group is a m-directing, deactivating substituent, so the
electrophile will attack at the meta position. Since all three canonical forms have one
electron-deficient carbon atom, none of these structures should contribute much more
to the overall resonance hybrid than any of the others.
H
H
CH=O
Br
H
CH=O
Br
Br
CH=O
(b) The amide functional group of acetanilide is bonded to the aromatic ring through the
nitrogen atom, so there is a lone pair of electrons in a position to be able to interact
with the π electron system of the ring. The group is an o,p-director, and and activating
group.
CH3
O C
CH3
CH3
O C
CH3
O C
O C
N H
N H
N H
N H
Br
Br
Br
Br
H
H
H
H
In this case, the canonical form on the extreme right is unique – every non-hydrogen atom
has a complete valence-shell octet of electrons, so we expect that this canonical form
will be by far the major contributor to the overall resonance hybrid for the structure of
this benzenonium ion.
Problem 19.14. Draw all the canonical forms for the most stable benzenonium ions
formed by the addition of Br+ either meta or para to the substituent in each of the
following aromatic compounds. Give reasons for your choice of benzenonium ion, and,
where appropriate, indicate which of the canonical forms will be the major contributor
to the overall resonance hybrid for the benzenonium ion.
(a) benzoic acid.
(d) nitrobenzene.
(g) fluorobenzene.
(i) benzonitrile.
(b) anisole.
(c) phenol.
(e) chlorobenzene.
(f) acetophenone.
(h) biphenyl (C6H5–C6H5).
(j) N,N-dimethylaniline.
Problem 19.15. Draw the structure of the major mononitration product expected from
the nitration of each of the following aromatic compounds. In each case, state whether
the reaction will occur more rapidly or less rapidly than the nitration of benzene under
the same conditions.
(a)
NO2
Me
OEt
(b)
(c)
N
O
(d)
CH2CH2Br
(e)
CF3
Electrophilic substitution in heterocyclic aromatic compounds
The data in Table 19.3 show that an aromatic ring participates more readily in electrophilic
aromatic substitution as it becomes more electron-rich. If the π electron density at a particular
731
AROMATIC COMPOUNDS I
Chapter 19 732
atom is increased, the relative rate of attack of an electrophile at that position increases. If the π
electron density at that position is decreased, the relative rate of attack at that position by an
electrophile decreases.
The average π electron density in benzene is one π electron per ring atom. The observed
orienting effects of substituents are, in part, a result of the effects of the substituent on the π
electron density at each position of the ring. In a formal sense, the π electron density in the sixmembered heterocyclic compounds is also one π electron per atom. However, there are several
minor canonical forms which one can draw for the pyridine molecule which are not reasonable
for benzene. In each of these canonical forms, there is a negative charge on nitrogen and a
positive charge on carbon.
N
••
••
••
••
N
••
N
••
••
N
N
••
In the conjugate acid of pyridine, the contribution of carbocation canonical forms to the
overall resonance hybrid is even more pronounced, since it does not involve charge separation.
N
H
••
••
N
H
N
H
••
N
H
N
H
The electronegative atom in pyridine changes the distribution of the π electron density so that
there is a net negative charge at the nitrogen and a net positive charge at the carbon atoms in
positions 2, 4 and 6. Pyridine should be less reactive towards electrophiles than benzene, and it is
– pyridine itself is about as reactive as nitrobenzene in electrophilic aromatic substitution. But.....
the first site of attack of any electrophile on a molecule is the HOMO of the molecule, and the
HOMO of the pyridine molecule is the lone pair on nitrogen. Thus, it is almost never the free
pyridine molecule which reacts with an electrophile, but the Lewis acid-Lewis base complex
formed by overlap of the pyridine HOMO with the Lewis acid LUMO. In this complex the
nitrogen carries a full formal positive charge, and this ion is even less reactive than pyridine, so
that electrophilic substitution occurs only under extreme reaction conditions. When it does occur,
electrophilic aromatic substitution in the pyridine ring occurs at position 3, but the Lewis acidLewis base complex of pyridine is so resistant to substitution that pyridine can be used as a
carrier for electrophiles in electrophilic aromatic substitution: the complex between pyridine and
bromine can be used for bromination reactions, and the pyridine-sulfur trioxide complex is a
good sulfonating reagent.
N
Br
Br
O
S O
N
O
N Br Br
O
N S O
O
In contrast to pyridine, the average π electron density in the five-membered heterocyclic
compounds is higher than in benzene (in a formal sense, 1.2 π electrons per ring atom). These
compounds are much more reactive towards electrophiles than benzene. In fact, furan and
pyrrole react with many electrophiles that only the most strongly activated benzene derivatives
will react with, and one must actually be careful to choose very mild reaction conditions to avoid
over-substitution in these compounds. They are, however, still less reactive towards electrophiles
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
than the corresponding aliphatic systems (the enol ethers and enamines). The intermediate
cations formed by addition of an electrophile to the five-membered aromatic heterocycles are
especially strongly stabilized by resonance, as shown for the addition of the electrophile to
pyrrole. In general, the rate of substitution is most rapid at the 2-position of the five-membered
aromatics, but substitution readily occurs at the 3-position if neither of the 2-positions is available.
E
••
N
H
E
E
•N•
H
N
H
H
H
E
H
E
••
H
N
H
attack of electrophile at 2- position
H
N
H
attack of electrophile at 3- position
The aromatic resonance energy of the five-membered aromatic heterocycles is lower than that
of benzene. The aromatic resonance stabilization energy of furan is 16 kcal mol-1 (66 kJ mol-1),
that of pyrrole is 21 kcal mol-1 (88 kJ mol-1), and that of thiophene is near 29 kcal mol-1 (121 kJ
mol-1). The resonance stabilization energy of thiophene is relatively close to that of benzene, and
thiophene reacts rather like an activated benzene. However, the resonance stabilization energy of
furan is close to 20 kcal mol-1 lower than that of benzene, and that of pyrrole is 15 kcal mol-1
lower than that of benzene, so that furan, especially, often reacts like a conjugated diene instead
of an aromatic compound. A good example of this is provided by the reaction between furan
and nitric acid in acetic anhydride: the product formed is not the substitution product, 2nitrofuran, but the product of 1,4-addition of acetyl nitrate to the diene. Likewise, furans
participate in the Diels-Alder reaction to give cyclohexenes.
HNO3/(CH3CO)2O
-5°C
O
O 2N
O
OCOCH3
O
+
O
O
O
O
O
O
O
The effect of the electrophile
Overall, the electrophilic aromatic substitution reaction is most strongly influenced by two
factors – the aromatic compound and the electrophile. We have just discussed the effects of the
aromatic compound itself (and of substituents on the aromatic ring) on the course of electrophilic
aromatic substitution. Now we will discuss the effects of the electrophile. Several commonly
used electrophiles in organic chemistry are listed in Table 19.5 in the approximately descending
order of their reactivity. The electrophiles at the top of the table are the most reactive, and will
react with practically all aromatic compounds to some degree, those in the middle of the table
will not react with aromatic compounds bearing deactivating groups, and those at the bottom of
the table will react with only the most strongly activated aromatic compounds.
The first step of reactions involving electrophiles at the top of the table are probably best
viewed as electrophilic addition reactions, where the driving force for the reaction comes from
the reactivity of the electrophile. In contrast to this, the first step of reactions involving
electrophiles at the bottom of the table may be best viewed as a nucleophilic addition reactions,
where the driving force for the reaction comes from the reactivity of the aromatic compound
itself.
Table 19.5 Common Electrophiles for Electrophilic Aromatic Substitution.
733
AROMATIC COMPOUNDS I
Electrophile
Chapter 19 734
Reagent Used
Product
Reactant Structural
Requirements
NO2+ (nitronium ion)
HNO3/H2SO4
Ar–NO2
none
"Cl+ " ("chloronium ion")
Cl2/AlCl3
Ar–Cl
none
+
"Br " ("bromonium ion")Br2/Fe or Br2/FeBr3
Ar–Br
none
SO3
H2SO4/SO3
Ar–SO3H
none
-----------------------------------------------------------R+ (alkyl cation)
RCl/AlCl3
Ar–R
no NO2, C=O, CN, or SO2
groups
R-C≡O+ (acylium ion)
RCOCl/AlCl3
Ar–CO–R
no NO2, C=O, CN, or SO2
groups
-----------------------------------------------------------XCH=NR+ (iminium ion)
DMF/POCl3
Ar–CHO
activating group
+
NO (nitrosonium ion)
HONO
Ar–NO
strong activating group
(NH2 or O–)
+
+
Ar–N2 (aryldiazonium ion)
Ar–N2
Ar–N=N–Ar′
strong activating group
(NH2 or O–)
CCl2 (dichlorocarbene)
KOH/CHCl3
Ar–CHO
strong activating group
(NH2 or O–)
CO2
Ar–CO2H
strong activating group
(NH2 or O–)
Problem 19.16. Electrophilic aromatic substitution of indole occurs more easily than
benzene, and it occurs in the heterocyclic ring at the 3- position. Electrophilic aromatic
substitution of quinoline occurs in the carbocyclic ring at the 5- and 8- positions, and it
occurs less readily than in benzene. Suggest reasons to account for for these
observations. [Hint: Consider the effects of resonance in the intermediate cations.]
E
3
E
5
E
N
H
E
N
H
8
N
+
N
N
E
Problem 19.17. Which of the two aromatic compounds in Problem 19.16 would you
expect to react with the electrophiles in the list below? Give reasons for your answer.
(a) nitronium ion.
(d) carbon dioxide.
19.7
(b) an acylium ion.
(c) an aryldiazonium ion.
REGIOCHEMISTRY OF REPRESENTATIVE
AROMATIC SUBSTITUTIONS
ELECTROPHILIC
The substitution of substituted benzenes and heteroaromatic compounds proceeds as would be
expected on the basis of the discussion in the previous section. Activated aromatic compounds
react rapidly with electrophiles under relatively mild conditions; deactivated aromatic compounds
require more reactive electrophiles and more vigorous reaction conditions for substitution to
occur. The reactions below are some typical examples of electrophilic substitution in compounds
other than benzene.
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
Nitration
The nitration of acetanilide occurs readily at low temperature to give a mixture of pnitroacetanilide and o-nitroacetanilide, while nitration of benzaldehyde requires more vigorous
conditions, and gives predominantly m-nitrobenzaldehyde. Nitration of five-membered aromatic
heterocyclic compounds occurs under extremely mild conditions: for example, thiophene can be
nitrated with nitric acid in acetic anhydride.
NHCOCH3
NHCOCH3
HNO3/H2SO4
0-2°C
CHO
NHCOCH3
+
(60%)
(19%)
O 2N
NO2
O 2N
fuming HNO3/H2SO4
CHO
(50%)
0-40°C
HNO3/(CH3CO)2O
S
S
(70-85%)
NO2
Halogenation
Halogenation of phenol, as expected, occurs much more readily than halogenation of benzene.
In fact, the aromatic ring of phenol is sufficiently activated towards electrophilic aromatic
substitution that phenol will react with bromine in the absence of a Lewis acid to give pbromophenol as the major product of the reaction.
OH
Br2/CS2/0-5°C
Br
OH
(81-84%)
With aqueous bromine at room temperature, the product of the reaction is 2,4,6tribromophenol, the compound in which every available ortho and para hydrogen is replaced.
Br
OH
Br2/H2O
OH
Br
Br
In contrast to the ease with which phenol is halogenated, the bromination of nitrobenzene
requires a ferric bromide catalyst and heating; m-bromonitrobenzene is the product formed.
NO2
Br2/Fe
135-145°C
Br
NO2
(74%)
Friedel-Crafts Reactions
The Friedel-Crafts acylation and alkylation reactions are important carbon-carbon bondforming reactions, but both have their limitations – they fail when the aromatic ring carries a
strongly electron-withdrawing group. In fact, it is for this reason that nitrobenzene is often used
as a solvent for the Friedel-Crafts reaction – it is a relatively good solvent for aluminum chloride,
but will not react with the electrophile formed.
CH3COCl
AlCl3
O
(86%)
CH3
735
AROMATIC COMPOUNDS I
Chapter 19 736
Activated aromatic compounds are acylated very readily as illustrated by the acylation of
thiophene with acetic anhydride in the presence of a catalytic amount of PPA.
O
(CH3CO)O
(70%)
PPA
S
S
Me
Formylation
When the aromatic compound is activated towards electrophilic aromatic substitution, one can
use a reagent composed of N,N-dimethylformamide and phosphorus oxychloride to formylate the
ring. This reaction is known as the Vilsmeier-Haack formylation, named after Anton
Vilsmeier and A. Haack, who first reported it. It is an excellent alternative to the Gattermann and
Gattermann-Koch reactions for formylating activated aromatic compounds.
The active
electrophile in the reaction is a chloroiminium ion, [ClCH=N(CH3)2]+
Me
Me
Me
POCl3/DMF/0°C→20°C/2 h
CHO
O
(96%)
O
Me
CHO
1) POCl3/DMF
N
H
(83%)
2) H2O
N
H
Sulfonation
Sulfonation of substituted benzenes proceeds as expected, with strongly activated aromatic
compounds (e.g. phenol) being subject to polysubstitution.
CH3
H2SO4/Δ
CH3
CH3
SO3H
+
SO3H
OH
OH
H2SO4/Δ
SO3H
HO3S
NO2
H2SO4/SO3/Δ
HO3S
NO2
Unlike the substitution reactions we have discussed so far, sulfonation is reversible, and an
arenesulfonic acid may be converted back to the aromatic hydrocarbon by treatment with
superheated steam. This reversibility allows the sulfonic acid group to be used as a blocking
group to prevent substitution in an aromatic ring, and permits it to be removed after the reaction
is complete, as in the following synthesis of o-bromophenol.
OH
OH
OH
SO3H
H2SO4
Δ
Br2/H2O
Br
SO3H
NaOH
HO3S
OH
H2SO4
H2O/200°C
HO3S
Br
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
Sample Problem 19.4. Write a mechanism to account for the formation of the product in
the following reaction.
OH
H
Answer:
H
OH
OH2
CH2
Problem 19.18. Write a mechanism to account for the formation of the product in each
of the following reactions.
Cl
(a)
AlCl3
H2SO4
(b)
What other product might have been formed in each of these reactions? Why do you
think that it was not formed as the major product?
Problem 19.19. Draw the structure of the major organic product expected when each of
the compounds in the list below is allowed to react with each of the reagents in the list
below it. If no reaction should occur, write "N/R".
Compounds:
(a) benzene.
(b) anisole.
(c) nitrobenzene.
(d) acetophenone.
(e) acetanilide.
(f) m-xylene.
(g) thiophene.
(h) benzonitrile.
(i) pyridine.
Reagents:
(1) CO/HCl/AlCl3/CuCl. (2) HNO3/H2SO4.
(3) C2H5COCl/AlCl3.
(4) Br2/Fe.
(5) H2SO4/Δ.
(6) (CH3)2C=CH2/HF.
(7) succinic anhydride/AlCl3.
(8) 1) DMF/POCl3; 2) H2O.
Electrophilic substitution in polysubstituted benzenes
When an aromatic ring carries two or more substituents, the influences of those substituents
will affect the overall chemistry of the ring. The influences of the substituents may reinforce each
other or they may oppose each other. In the case where substituent influences reinforce each
other, the outcome of the electrophilic aromatic substitution is easy to predict. For example,
nitration of m-dinitrobenzene, where both substituents are m-directors, gives 1,3,5-trinitrobenzene
on nitration; the nitro group is introduced into the only position meta to both nitro groups.
NO2
O 2N
NO2
this position is meta to both
nitro groups
NO2
NO2
Bromination of p-nitroanisole, where one substituent is a m-director and one is an o,p-director,
gives 2-bromo-4-nitroanisole; the bromine is introduced meta to the m-directing nitro group and
ortho to the o,p-directing methoxy group.
737
AROMATIC COMPOUNDS I
this position is meta to the
nitro group and ortho to the
methoxy group
Chapter 19 738
NO2
Br
CH3O
NO2
CH3O
Monobromination of m-dimethoxybenzene, where both substituents are o,p-directing, gives 1bromo-2,4-dimethoxybenzene; the bromine is introduced ortho to one substituent and para to
the other.
this position is ortho to one
methoxy group and para to
the other
CH3O
CH3O
OCH3
OCH3
Br
Where the directing effects of the two substituents oppose each other (e.g. in m-nitroanisole),
the substituent bearing the lone pair almost always determines the major product of the reaction.
In m-nitroanisole, the methoxy group activates positions 2, 4 and 6 of the ring; the nitro group
deactivates those same positions. However, when an electrophile adds to one of these positions,
one can still write one canonical form for the benzenonium ion where every non-hydrogen atom
has a complete outer-shell octet of electrons – and this, we know, represents an exceptionally
stable situation. Monobromination of m-nitroanisole gives 1-bromo-2-nitro-4-methoxybenzene as
the major product, in spite of the fact that this requires that the electrophile add to the ring ortho
to a nitro group instead of meta to it. Here, the substituent with the lone pair of electrons
determines the outcome of the reaction.
this position is para to the
methoxy group and ortho to
the nitro group.
O 2N
O 2N
OCH3
OCH3
Br
Substitution in polycyclic aromatic hydrocarbons
Polycyclic aromatic hydrocarbons generally react as activated aromatic compounds. In
naphthalene, substitution may occur at either the 1- position to give α-substituted naphthalenes,
or at the 2- position to give β-substituted naphthalenes. In general, the formation of the 1substitution product is favored kinetically.
Br
Br2/CCl4
Δ
(73%)
Me
CH3COCl/AlCl3
CS2
O
(92%)
Electrophilic substitutions of phenanthrene and anthracene are characterized by the fact that
products formed by electrophilic addition across the 9- and 10- positions can often be isolated in
these compounds. This is almost certainly due to the fact that the initial addition of the
electrophile at this position results in the formation of two benzene-type rings, with resonance
stabilization energies of 36 kcal mol-1 each, compared to resonance energies of 84 kcal mol-1
(anthracene) and 92 kcal mol-1 (phenanthrene). The loss of stabilization energy due to addition is
about the same as the loss of stabilization energy in addition reactions of furan. The addition
products of anthracene and phenanthrene, however, undergo facile elimination to restore the fully
aromatic ring systems in which there has been overall substitution at the 9-position.
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
O
CH3
CH3COCl/AlCl3
(65%)
CS2
CH3
CH3COCl/AlCl3
C
O
(71%)
Problem 19.20. Draw the structure of the major monosubstitution product obtained from
the reaction between of each of the following compounds with the electrophiles listed
below. If no reaction should occur, write "N/R".
Compounds:
Cl
(a)
(b)
(e)
CH3
(h)
CH3CONH
OCH3
Br
OCH3
(c)
O 2N
(f)
CH=O
(g)
MeO
Cl
(d)
HO
CO2H
O 2N
CO2CH3
Reagents:
(1) HNO3/H2SO4.
(4) CH3COCl/AlCl3.
(i)
(j)
CH3
(2) SO3/H2SO4.
(5) Br2/Fe.
(3) Cl2/AlCl3.
(6) (CH3)2C=CH2/H+ .
Reaction synopsis
Vilsmeier-Haack formylation
POCl3/DMF
Reagents:
POCl3/DMF.
Requires activated aromatic compound.
OH
CHO
739
AROMATIC COMPOUNDS I
Chapter 19 740
19.8 SUMMARY
In this chapter, we have begun the study of aromatic compounds and their chemistry.
Aromatic compounds are characterized by unusual stability, and by undergoing substitution by
electrophiles rather than addition, as is the case with alkenes. Aromatic compounds may be
carbocyclic (e.g. benzene) or heterocyclic. heterocyclic compounds may be based on sixmembered rings (pyridine, quinoline, isoquinoline) or five-membered rings (furan, thiophene,
pyrrole, indole). Compounds may be monocyclic (benzene, pyridine, pyrrole) or polycyclic
(naphthalene, anthracene, phenanthrene, the acenes, quinoline, isoquinoline, indole).
The structural requirements for aromaticity were established by Hückel: 1. All aromatic
compounds are planar; 2. All aromatic compounds are cyclic; 3. All aromatic compounds have
a linearly conjugated, delocalized π bond system; and 4. All aromatic compounds have 4n+2 π
electrons delocalized in the π bonding system, where n is an integer. Compounds satisfying the
first three requirements, but with 4n π electrons are antiaromatic.
The molecular orbitals of cyclic, conjugated π compounds occur as a single lowest-energy
occupied molecular orbital, and all the remaining orbitals occur as degenerate pairs wherever
possible. The relative energies of the molecular orbitals of cyclic, conjugated π-bonded
compounds can be obtained by drawing the regular polygon corresponding to the number of
participating p orbitals on its vertex. In benzene (six p orbitals, a hexagon), there are two
degenerate HOMO's, each with one nodal plane perpendicular to the ring, and two degenerate
LUMO's with two nodal planes perpendicular to the ring.
Aromatic compounds are stabilized by resonance. The resonance stabilization energy of
benzene is estimated to be 30-36 kcal mol-1, depending on the method used to make the
estimate. The resonance stabilization energy of pyridine is very similar to that of benzene; the
resonance stabilization energies of polycyclic aromatic compounds (PCAH's) increase as the
number of fused aromatic rings increases, but the average resonance energy per ring decreases;
resonance stabilization energies of five-membered heterocyclic aromatic rings are less than that of
benzene.
The definitive reaction of aromatic compounds is electrophilic aromatic substitution.
Electrophilic aromatic substitution occurs by a two-step mechanism. In the first step, the
electrophile adds to the aromatic π electron system to give an intermediate benzenonium ion; this
reaction destroys the aromaticity in the ring. In the second step, a proton is lost to give the
substitution product; in this step, the aromaticity of the ring is restored.
Substituents affect both the rate and the orientation of substitution. Substituents which
accelerate the reaction are termed activating groups; substituents that retard the reaction are
termed deactivating groups. All activating groups are o,p-directing. Except for the halogens,
which are o,p-directors, all deactivating groups are m-directing.
Activating Groups
o,p- Directing
Groups
–O–
–NR2
–OH
–OR
–NR–CO–R
–O–CO–R
–R
m-Directing
Groups
none known
Deactivating Groups
o,p- Directing
Groups
m-Directing
Groups
Cl, Br, I
–NR3+
–NO2
–SO2–R
–C≡N
–CO–R
–CO-OR
–CO–NR2
Electrophilic substitution is also affected by the electrophile, as well as the aromatic compound
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
itself. Electrophiles may be classified broadly as strong electrophiles, which give substitution
products with all aromatic compounds, moderately strong electrophiles, which do not react with
strongly deactivated aromatic rings, and weak electrophiles, which require activated aromatic
rings for substitution to occur.
Strong electrophiles are nitronium ion (NO2+ : HNO3/H2SO4), activated halogens ("halonium
ions", X+ : Cl2/AlCl3, Br2/Fe, Br2/FeBr3), and sulfur trioxide (SO3: also H2SO4). Moderately
strong electrophiles, which will not react with nitrobenzene, are alkyl cations (R+ : RCl/AlCl3) and
acylium ions (RC≡O+ : RCOCl/AlCl3). Weak electrophiles are iminium ions (e.g. ClCH=NMe2+ :
POCl3/DMF), nitrosonium ion (NO+ : HONO/H+ ). diazonium ions (ArN2+ ), and even carbon
dioxide. Weak electrophiles do not react with benzene or toluene, but require a stronger
activating group.
Preferred orientation of substitution is determined by the electron-releasing substituents,
especially if one carries a lone pair of electrons. m-Nitroanisole gives the product of substitution
at the para position, in spite of the fact that this requires that the electrophile add ortho to the
nitro group.
Six-membered heterocyclic arenes react only with strong electrophiles due to the deactivating
influence of the heteroatom. Substitution of pyridines occurs at the 3- position; substitution of
quinolines and isoquinolines occurs in the benzenoid ring rather than the heterocyclic ring. Fivemembered heteroaromatic compounds are activated towards electrophilic aromatic substitution
relative to benzene due to their higher π electron density per ring position. Substitution occurs at
the 2- position in monocyclic compounds and at the 3- position of indole and its analogs.
Polycyclic aromatic hydrocarbons react with electrophiles as activated arenes. Substitution in
naphthalene occurs preferentially at the 1- position, and in anthracene and phenanthrene it occurs
preferentially at the 9- position. Electrophilic substitution in anthracene and phenanthrene may
occur in two stages: addition to give the 9,10-adduct, and then elimination; the adduct can often
be isolated in these systems.
19.9 GLOSSARY OF IMPORTANT TERMS
Activating Groups – substituents that increase the rate of electrophilic aromatic substitution
compared to benzene. Activating groups are all o,p-directors.
Acylium Ion – the cation R-C≡O+ , the active electrophile in the Friedel-Crafts acylation.
Arene – an aromatic compound; often designated by the symbol Ar–H.
Aromatic – a compound with a planar, cyclic, conjugated π-electron system containing 4n+2
electrons, where n is an integer.
Aromatic Resonance Stabilization Energy – the additional stability of the aromatic compound
over the corresponding hypothetical cyclic, conjugated, non-aromatic compound. For
benzene, the aromatic resonance stabilization energy is approximately 36 kcal mol-1.
Aryl Group – the group generated by removal of a hydrogen from an arene; often designated
by the symbol Ar–.
Benzenonium Ion – the resonance-stabilized cation formed by addition of an electrophile to
the π system of an arene.
Benzyl Group – the group C6H5CH2–; not an aryl group.
Deactivating Groups – substituents that decrease the rate of electrophilic aromatic substitution
compared to benzene. All m-directors are deactivating groups, as are the halogens.
Directing Effects – the propensity of a substituent on an aromatic ring to direct an incoming
electrophile to a particular position relative to the substituent itself.
o,p-directors – groups which direct the incoming electrophile to attack at a position ortho
or para to the substituent. The alkyl groups and substituents where the atom bonded
to the ring carries a lone pair of electrons are o,p-directing groups.
741
AROMATIC COMPOUNDS I
Chapter 19 742
m-directors – groups which direct the incoming electrophile to attack at a position meta to
the substituent. The nitro (–O–N+ =O), carbonyl (C=O), cyano (C≡N) and sulfonyl
(O=S=O) groups are common m-directing groups.
Electrophilic Aromatic Substitution – a reaction in which a hydrogen atom bonded to an
aromatic ring is replaced by an electrophile.
Formylation – the conversion of an arene to an aromatic aldehyde (Ar–CH=O).
Friedel-Crafts Acylation – the conversion of an arene to an aryl ketone (Ar-COR) by
reaction with an acid chloride or anhydride and aluminum chloride.
Friedel-Crafts Alkylation – the conversion of an arene to an alkylarene (Ar–R) by reaction
with an alkyl halide and aluminum chloride or another source of alkyl cations.
Gattermann Aldehyde Synthesis – the conversion of an arene to an aromatic aldehyde by zinc
cyanide and hydrogen chloride.
Gattermann-Koch Reaction – the conversion of an arene to an aromatic aldehyde by carbon
monoxide and hydrogen chloride in the presence of an aluminum chloride catalyst.
Nitration – the conversion of an arene to a nitroarene (Ar–NO2) by nitronium ion.
Nitronium Ion – NO2+ ; one of the strongest electrophiles known.
Phenyl Group – the group C6H5–; the simplest aryl group known.
Polycyclic Aromatic Hydrocarbons – fused-ring arenes with two or more aromatic rings.
Sulfonation – the conversion of an arene to the arenesulfonic acid (Ar–SO3H).
19.10 ADDITIONAL PROBLEMS
19.21. Draw the structures of each of the following compounds, all of which are
commercially available.
(a) p-dichlorobenzene.
(b) 2,4-dinitrofluorobenzene.
(c) 2-chloropyridine.
(d) benzoic acid.
(e) 1-phenylethanol.
(f) 4-bromoanisole.
(g) 1-bromo-3-iodobenzene.
(h) 8-hydroxy-5-nitroquinoline.
(i) 5-isopropyl-3-methylphenol
(j) 4-hydroxyphenylacetic acid
(k) 1-phenyl-1-cyclopentanecarbonitrile (l) 4-chloro-3-nitrobenzophenone
(m) 3,5-dinitrobenzonitrile
(n) ethyl 2-thiopheneacetate
(o) phenyl benzoate
(p) benzanilide (N-phenylbenzamide)
(q) 5-cyanoindole
(r) 2,5-pyridinedicarboxylic aid
(s) 2-isopropylaniline
(t) 2-benzylaniline
(u) pentafluorobenzoyl chloride
(v) 3-chlorobenzyl chloride
(w) 4-methoxyphenol
(x) 3-benzoyloxybenzyl alcohol
(y) BHT ( a preservative: 2,6-di-tert-butyl-4-methylphenol)
(z) benzoin (1,2-diphenyl-2-hydroxy-1-ethanone)
19.22. Draw all possible resonance structures for each of the following polycyclic aromatic
hydrocarbons.
(a)
(b)
(c)
(d)
19.23. Draw the structure of the major organic product or products expected from the
substitution of each of the following compounds by each of the electrophilic reagents listed.
If no reaction should occur, write "N/R."
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
Electrophiles:
(1) Br2/Fe.
(4) (CH3)3CCl/AlCl3.
(7) HNO3/(CH3CO)2O.
(10) POCl3/DMF.
(2) HNO3/H2SO4.
(5) C6H5COCl/AlCl3.
(8) H2SO4/SO3.
(11) cyclohexanol/HF.
(3) CO/HCl/AlCl3.
(6) Cl2/AlCl3.
(9) Zn(CN)2/HCl.
(12) (CH3)2C=CH2/HF.
Compounds:
OH
(a)
(b)
HO
OCH3
CHO
(c)
OCH
(d)
OH
NH2
CHO
O
(f)
H2N
(g)
OCH3
(j)
N(CH3)2
O
C
CH2CH3
(k)
O 2N
CN
(p)
C
O
CH2CH3
CN
(m)
CH3O
H
N
(i)
NO2
(l)
(n)
NH2
C
O
O 2N
CN
CN
CH3
(o)
(h)
(e)
CH3
(q)
Cl
(r)
CH3O
OCH3
CH3
N
(s)
Br
O
(t)
O
H
N
(u)
O
O
O
O
(v)
N
H
(w)
(x)
O
(y)
N
(z)
O
(aa)
N
CH3
(bb)
(cc)
S
(dd)
19.24. Which of the following compounds is (are) aromatic? Give your reasons.
(a)
(b)
(c)
(d)
H
O
(e)
(f)
O
O
(g)
H
H H
H
H
19.25. Tropone (below left) is a ketone whose conjugate acid has a pKa of 4.8 – essentially
the same as the pKa for acetic acid. By comparison, the pKa of the conjugate acid of
cyclohexanone (below right) is –7.0, close to that for HCl. Tropone has also been found to
have a much larger dipole moment than many ketones. Propose a reason or reasons to
account for these observations.
743
AROMATIC COMPOUNDS I
Chapter 19 744
OH
O
OH
pKa = 4.8
O
pKa = –7.0
19.26. Arrange the monosubstituted benzene derivatives in Problem 19.23 in increasing
order of their reactivity towards electrophiles (least reactive first). Give reasons for your
choice.
19.27. Arrange the disubstituted benzene derivatives in Problem 19.23 in the approximately
decreasing order of their reactivity towards electrophiles (most reactive first). Note that
there may be several compounds (e.g. m and o) whose reactivity may be similar; group
these compounds and place the group in its place in the order. Where two or more
compounds are placed in the same group, give your reasons for doing so, and give reasons
for the order of reactivity which you propose.
19.28. Draw the structures of the monosubstitution, disubstitution, and trisubstitution
products which could be formed in the reaction between benzene and the electrophiles
given in Problem 19.23. Where only monosubstitution product will be obtained, explain
why only the monosubstitution product forms.
19.29. Each of the following electrophilic substitution reactions has been used as one step in
the synthesis of a naturally-occurring compound. Draw the structures of all the products
expected from each reaction, and indicate which should be formed in major amounts.
Give reasons for your choice.
OH
OCOCH3
(a)
CH3
CO2H
CH3O
(b)
CCl4
Br2
OH
NHCOCF3
(c)
CHO
CH3COCl/AlCl3
HO
OCH3
HF
PPA
(f)
CH3O
O
CO2H
OCH3
Zn(CN)2/HCl
(g)
(i)
O
PPA/Δ
(h)
HO2C
OH
OCOCH3
BF3
OCH3
CH3
HO
CH3CH2CO2H
CH3
HO
O
O
(e)
(d)
Et2O/25°C
CO2CH3
OCH3
OH O
HNO3 (1 eq.)
POCl3/DMF
CH2Cl2
(j)
CO2H
N
CH3
HNO3/(CH3CO)2O
-15°C
19.30. Earlier in this chapter, the statement is made that the orientation of electrophilic
substitution in disubstituted benzenes where the ring carries both an electron-donating
Chapter 19
AROMATICITY & ELECTROPHILIC AROMATIC SUBSTITUTION
group with a lone pair of electrons and an electron-withdrawing group is always
determined by the electron-donating group. Using the example given (the bromination of
m-nitroanisole), draw resonance structures for the possible intermediate benzenonium ions
and use them to suggest a reason why this should be so. Why does the nitration of mnitrotoluene give 3,5-dinitrotoluene as the major product?
19.31. One method for predicting the most likely position for attack of an electrophile on a
polycyclic aromatic hydrocarbon involves drawing all the possible resonance contributors
and finding the atoms most often involved in a double bond. The method is exemplified
below for phenanthrene: note that there is a double bond between carbons 9 and 10 in
four of the contributors, while no other pair of carbon atoms is involved in more than
three double bonds. Hence, one predicts that the phenanthrene molecule will react most
readily with electrophiles at the 9 and 10 positions.
Apply this method to predict the most likely position of attack of an electrophile on the
molecules below:
(a)
(b)
(c)
(d)
19.32. The compound below, C15H12O2 is chemically related to the anthocyanin pigments,
which are the compounds responsible for the colors of many flowers, including red roses,
blue cornflowers and violets. When this compound is treated with hydrochloric acid, a salt
is obtained. What is the structure of the salt, and why can it be isolated?
OH
HCl
O
C15H11OCl
19.33. When the compound below is treated with dilute acid or base, it rearranges to αnaphthol. Write a mechanism to rationalize this transformation. Why does the reaction
occur at all?
OH
O
H
745