Documenti di Didattica
Documenti di Professioni
Documenti di Cultura
I O CO2H
I O
H NH2 OH
HO I CO2H
OH O OH OH
I thyroxine: human hormone
regulating metabolic rate aklavinone:
tetracycline antibiotic
MeO OR
H
HO O
NHMe
MeO
MeO OR
O
colchicine: OH calistephin:
anti-cancer agent HO2C natural red flower pigment
from the autumn crocus OMe
NH CO2H
Suggested
solution
Truly
aromatic
rings
are
marked
with
bold
lines.
Thyroxine
has
two
benzene
ringsobviously
aromaticand
thats
that.
Aklavinone
also
has
two
aromatic
benzene
rings
and
we
might
argue
about
ring
2.
It
has
four
electrons
as
drawn,
and
you
might
think
that
you
could
push
electrons
round
from
the
OH
groups
to
give
ring
2
six
electrons
as
well.
But
if
you
try
it,
youll
find
you
cant.
2
Solutions
Manual
to
accompany
Organic
Chemistry
2e
I O CO2H
I O
H NH2 1 2 3 OH
HO I CO2H
OH O OH OH
I
MeO MeO
H H
NHMe NHMe
MeO MeO
MeO MeO
O O
OMe OMe
Methoxatin
has
one
benzene
ring
and
one
pyrrole
ring
an
example
of
an
aromatic
compound
with
a
five-membered
ring.
The
six
electrons
come
from
two
double
bonds
and
the
lone
pair
on
the
nitrogen
atom.
The
middle
ring
is
not
aromaticeven
if
you
try
drawing
other
delocalised
structures,
you
can
never
get
six
electrons
into
this
ring.
HO2C HO2C
NH CO2H NH CO2H
O CO2H O CO2H
O O
Solutions
for
Chapter
21
Electrophilic
Aromatic
Substitution
3
PROBLEM
2
First,
as
some
revision,
write
out
the
detailed
mechanism
for
these
steps.
NO2
NO2
HNO3 + H2SO4 NO2
In
a
standard
nitration
reaction
with,
say,
HNO3
and
H2SO4,
each
of
these
compounds
forms
a
single
nitration
product.
What
is
its
structure?
Explain
your
answer
with
at
least
a
partial
mechanism.
CO2H
NHAc
Me O
Suggested
solution
The
basic
mechanisms
for
the
formation
of
NO2+
and
its
reaction
with
benzene
appear
on
p.
476
of
the
textbook.
Benzoic
acid
has
an
electron-
withdrawing
substituent
so
it
reacts
in
the
meta
position.
The
second
compound
is
activated
in
all
positions
by
the
weakly
electron
donating
alkyl
groups
(all
positions
are
either
ortho
or
para
to
one
of
these
groups)
but
will
react
at
one
of
the
positions
more
remote
from
the
alkyl
groups
because
of
steric
hindrance.
CO2H CO2H
O2N
NO2
4
Solutions
Manual
to
accompany
Organic
Chemistry
2e
Me Me NO2 O O
PROBLEM
3
How
reactive
are
the
different
sites
in
toluene?
Nitration
of
toluene
produces
the
three
possible
products
in
the
ratios
shown.
What
would
be
the
ratios
if
all
the
sites
were
equally
reactive?
What
is
the
actual
relative
reactivity
of
the
three
sites?
You
could
express
this
as
x:y:1
or
as
a:b:c
where
a+b+c
=
100.
Comment
on
the
ratio
you
deduce
NO2
Me
Me Me Me +NO2
HNO3
+ +
H2SO4 NO2
59% yield 4% yield 37% yield
Suggested
solution
As
there
are
two
ortho
and
two
meta
sites,
the
ratio
if
all
were
equally
reactive
would
be
2:2:1
o:m:p.
The
observed
reactivity
is
30:2:37
or
15:1:18
or
43:3:54
depending
on
how
you
expressed
it.
The
ortho
and
para
positions
are
roughly
equally
reactive
because
the
methyl
group
is
electron-donating.
The
para
is
slightly
more
reactive
than
the
ortho
because
of
steric
hindrance.
The
meta
position
is
an
order
of
magnitude
less
reactive
because
the
intermediate
is
not
stabilised
by
electron-
donation
(-conjugation)
from
the
methyl
group.
Solutions
for
Chapter
21
Electrophilic
Aromatic
Substitution
5
PROBLEM
4
Draw
mechanisms
for
these
reactions
and
explain
the
positions
of
substitution.
OH OH OH
Br
HNO3 Br2
NO2 NO2
Cl Br
Br
Cl
AlCl3
Suggested
solution
The
OH
group
has
a
lone
pair
of
electrons
and
dominates
reactivity
and
selectivity.
Steric
hindrance
favours
the
para
product
in
the
first
reaction.
The
bromination
has
to
occur
ortho
to
the
phenol
as
the
para
position
is
blocked.
6
Solutions
Manual
to
accompany
Organic
Chemistry
2e
OH OH OH OH OH
Br Br Br Br
H
Br Br
Br
Cl Cl
and repeat
AlCl3
Cl
Cl
PROBLEM
5
Nitration
of
these
compounds
gives
products
with
the
1H
NMR
spectra
shown.
Deduce
the
structures
of
the
products
and
explain
the
position
of
substitution.
WARNING:
do
not
decide
the
structure
by
saying
where
the
nitro
group
ought
to
go!
Chemistry
has
many
surprises
and
it
is
the
evidence
that
counts.
NO2 H
? 7.77 (4H, d, J 10)
8.26 (4H, d, J 10)
Cl H
NO2 7.6 (1H, d, J 10)
? 8.1 (1H, dd, J 10,2)
Cl 8.3 (1H, d, J 2)
F H
NO2
? 7.15 (2H, dd, J 7,8)
8.19 (2H, dd, J 6,8)
Solutions
for
Chapter
21
Electrophilic
Aromatic
Substitution
7
Suggested
solution
The
first
product
has
only
eight
hydrogens
so
two
nitro
groups
must
have
been
added.
The
molecule
is
clearly
symmetrical
and
the
coupling
constant
is
right
for
neighbouring
hydrogens
so
a
substitution
on
each
ring
must
have
occurred
in
the
para
position.
Note
that
the
hydrogen
next
to
the
nitro
group
has
the
larger
shift.
We
can
deduce
that
each
benzene
ring
is
an
ortho,para-directing
group
on
the
other
because
the
intermediate
cation
is
stabilised
by
conjugation.
H
NO2
NO2
H
O2N NO2 Vicinal
(ortho)
coupling
constants
in
benzene
rings
are
NO2 typically
8-10
Hz;
meta
coupling
7.77 H H 8.26 constants
are
typically
<2
Hz:
see
p.
(4H, d, J 10) 295-6
o
f
the
textbook.
(4H, d, J 10)
The
hydrogen
count
reveals
that
the
next
two
products
are
mono-
nitro
compounds.
There
are
two
hydrogens
ortho
to
nitro
in
the
second
compound
and
one
of
them
also
has
a
typical
ortho
coupling
to
a
neighbouring
hydrogen
while
the
other
has
only
a
small
coupling
(2
Hz)
which
must
be
a
meta
coupling.
Substitution
has
occurred
para
to
one
of
the
chlorines
and
ortho
to
the
other.
The
chlorines
are
ortho,para-
directing
thus
activating
all
remaining
positions
so
steric
hindrance
must
explain
the
site
of
nitration.
H 1H, d, J 2
H
Cl NO2 Cl Cl NO2
NO2
The
idea
that
heteronuclear
Cl Cl H couplings
leave
unpaired
coupling
Cl constants
1H, dd, J 10,2 in
the
1H
NMR
spectrum
1H, d, J 10 H
in
the
green
box
on
p.
is
explained
416
of
the
textbook.
The
third
compound
has
the
extra
complication
of
couplings
to
fluorine.
The
coupling
of
7
Hz
shown
by
one
hydrogen
and
6
Hz
shown
by
the
other
must
be
to
fluorine
as
they
occur
once
only.
The
symmetry
of
the
compound
and
the
typical
ortho
coupling
between
the
hydrogens
(8
Hz)
shows
that
para
substitution
must
have
occurred.
8
Solutions
Manual
to
accompany
Organic
Chemistry
2e
F F F
H
NO2 H NO2
NO2 7.15 (2H, dd, J 7,8)
H
8.19 (2H, dd, J 6,8)
PROBLEM
6
Attempted
Friedel-Crafts
acylation
of
benzene
with
t-BuCOCl
gives
some
of
the
expected
ketone
A
as
a
minor
product,
as
well
as
some
t-butylbenzene
B,
but
the
major
product
is
the
substituted
ketone
C.
Explain
how
these
compounds
are
formed
and
suggest
the
order
in
which
the
two
substituents
are
added
to
form
compound
C.
O
O
AlCl3
Cl + +
benzene
A B C O
Suggested
solution
The
expected
reaction
to
give
A
is
a
simple
Friedel-Crafts
acylation
with
the
usual
acylium
ion
intermediate.
O
O O
H
Cl A
Product
B
must
arise
from
a
t-butyl
cation
and
the
only
way
that
might
be
formes
is
by
loss
of
carbon
monoxide
from
the
original
acylium
ion.
Such
a
reaction
happens
only
when
the
resulting
carbocation
is
reasonably
stable.
H
O
B
Solutions
for
Chapter
21
Electrophilic
Aromatic
Substitution
9
O
AlCl3
+
Cl
C O
That
answers
the
question
but
you
might
like
to
go
further.
Both
A
and
C
are
formed
by
the
alkylation
of
benzene
as
the
first
step.
The
decomposition
of
the
acylium
ion
is
evidently
faster
than
the
acylation
of
benzene.
However,
when
B
reacts
further,
it
is
mainly
by
acylation
as
only
a
small
amount
of
di-t-butyl
benzene
is
formed.
Evidently
the
decomposition
of
the
acylium
ion
is
slower
than
the
acylation
of
B!
This
is
not
unreasonable
as
the
t-butyl
group
accelerates
electrophilic
attackbut
it
is
a
dramatic
demonstration
of
that
acceleration.
PROBLEM
7
Nitration
of
this
heterocyclic
compound
with
the
usual
HNO3/H2SO4
mixture
gives
a
single
nitration
product
with
the
1H
NMR
spectrum
shown
below.
Suggest
which
product
is
formed
and
why.
H
3.04 (2H, t, J 7 Hz)
3.68 (2H, t, J 7 Hz)
C8H8N2O2 6.45 (1H, d, J 8 Hz)
N 7.28 (1H, broad s)
H
7.81 (1H, d, J 1 Hz)
7.90 (1H, dd, J 8, 1 Hz)
Suggested
solution
The
two
2H
triplets
and
the
broad
NH
signal
show
that
the
heterocyclic
ring
is
intact.
One
nitro
group
has
been
added
to
the
benzene
ring.
The
proton
at
7.81
with
only
one
small
(meta)
coupling
must
be
between
10
Solutions
Manual
to
accompany
Organic
Chemistry
2e
the
nitro
group
and
the
other
ring
and
is
marked
on
the
two
possible
structures.
Ha
HNO3 O2N
or
H2SO4 O2N N
N N H
H H Hb
MeO
A + B both C12H16O
Br2 Br2
OH
? ?
Suggested
solution
The
reaction
is
a
Friedel
Crafts
cyclisation,
as
you
could
have
deduced
by
the
simple
loss
of
water.
The
resulting
cation
could
cyclise
in
two
ways,
arbitrarily
called
A
and
B.
Steric
hindrance
suggests
that
A
would
be
the
more
likely
product.
Solutions
for
Chapter
21
Electrophilic
Aromatic
Substitution
11
MeO H
H A
OH2
MeO MeO
B
MeO
Br2 Br2
A B MeO + MeO
Br
Br Br
12
Solutions
Manual
to
accompany
Organic
Chemistry
2e
PROBLEM
9
On
p.
479
of
the
textbook
we
explain
the
formation
of
2,4,6-tribromophenol
by
bromination
of
phenol
in
water.
It
looks
as
though
we
can
go
no
further
as
all
the
ortho
and
para
positions
are
brominated.
But
we
can
if
we
treat
the
tribromo-compound
with
bromine
in
an
organic
solvent.
Account
for
the
formation
of
the
tetrabromo-compound.
OH OH O
Br2 Br Br Br2 Br Br
Br
O
CF3 Br CF3
Br
+
90%
NMe2 NMe2 yield
Br Br
Suggested
solution
Phenol
is
so
reactive
that
the
fourth
bromine
adds
in
the
para
position.
Now
the
molecule
has
a
problem
as
there
is
no
hydrogen
on
that
carbon
to
be
lost.
So
the
phenolic
hydrogen
is
lost
instead.
It
is
surprising
but
revealing
that
this
loss
of
aromaticity
is
preferred
to
the
alternative
bromination
at
the
meta
position.
H
OH O O
Br Br Br Br Br Br
Br Br Br Br
Br Br Br
Note
that
the
meta
directing
Solutions
for
Chapter
21
Electrophilic
Aromatic
Substitution
13
effect
of
the
deactivating
CF3
group
is
irrelevant
(see
p.
491
of
the
textbook).
OH
Br Br
O
Br Br
Br
+
Br Br
Br H Br
CF3
CF3 CF3
NMe2
NMe2 NMe2