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Mechanisms of free-radical aromatic substitution
TetrahedronLetters No. 17, pp. 749-753, 1962. Per9amon Press Ltd. Printed in Great Britain.
WECHANISMSOF FREE-RADICALAROMATIC SUBSTITUTION E.L. Eliel, M. Eberhardt and 0. Simamura Department of Chemistry and RadiationLaboratorp University of Notre Dame, Notre Dame, Indiana
S.
Meyerson
Research and DevelopmentDepartment,American Oil Company, Whiting, Indiana (Received26 May 1962) 1 SINCE Hey's and Waters' studies on free-radicalaromatic substitution, such diverse reactions as the Gomberg-Bachmannreaction and the decompoarylazotriphenylmethanes and diaroyl sition of nitrosoacetanilides, peroxides in aromatic substrateshave been widely assumed to proceed by the same general mechanism once the substitutingaryl radicals are gener2 ated.
Work in DeTar's laboratory3and ourslcy5has shown that an important
contributingstep in the free-radicalarylationof benzene by diaroyl peroxides is disproportionationr
* Supported under contractwith the U.S. Atomic Energy Commission. 1 D.F. Hey, J. Chem. Sot. 1966 (1934);D.H. Hey and W.A. Waters, Chem. Rev. 2 a, 169 (1937). D.R. Augood and G.H. Williams,Chem. Rev. 12, 123 (1957);G.H. Williams, HomolvticAromatic SubstitutionChap. 4. Pergamon Press, New York (1960). See, however, H. Zollinger,&iazo and Azo Chemistry pp. 153-159, Interscience,New York (1961), for a contrary view. 3 D.F. DeTar and R.A.J. Long, J. Amer. Chem. Sot. @, 4742 (1958);D.F. DeTar, Abstracts.SeventeenthNational Oraanic ChemistrySvmoosium American Chem. Sot.. Bloominaton.Indiana, 1961, p. 59. 4 E.L. Eliel, S. Meyerson, Z. Welvart and S.H. Wilen, J. Amer. Chem. SOC.
'B, 2936 (1960). _' M. Eberhardt and E.L. Eliel, J. Ora. Chem. 2, 749
2289 (1962).
Mechanisms
750
We have now found
of
evidence
arylazotriphenylmethanes mediates
peroxides
are:
in the
(a)
diaroyl
arylation
arylbenzene
biaryl-A2
of
(I)
for
formation
of
formed4
arylation
extent,
- due,
and
(II)
as inter-
from arylation
with
(E.
could
0.15
of nitrosoacetanilide
survived
in dilute
(0.02
with
be detected (~a.
reaction.
(cf.
ref.
appearance oxidation
of
the
of of di-
these
criteria
nitrosoacetanilides
0.015
hi) solution
and with
of
in either
after
decompo-
in benzene.
solutions,
In control
3)
effect
discrimination
by gas chromatography
in the decomposition
M) solution
of
analog.
was added to the dilute
found
of
M)
content
isotopic (c)
(0.02
isotope
or phenylazotriphenylmethane
the arylation
was readily
to
diaroyl
M) solutions
We have now applied
e-chloro
M) or dilute
(0.2
as a result
benzene-d
and its
in dilute3
from the deuterium
radicals;
species.
with
an apparent
in part,
benzene-&
(II)
arylation
(II)
(b)
of hydrobiaryl of
of
in concentrated5
at least
of benzene.and
When dihydrobiphenyl
about
75 per cent
experiments, benzoyl
6
dihydrobi-
peroxide
and even at concentrations
in benzene as high
M. 5
Whereas appreciable
6
fashion
dihydrobiaryls
as computed
dihydrobiaryl
concentrated
sition
No.17
nitrosoacetanilides
the mechanism
benzene-d
No dihydrobiphenyl
as 0.2
substitution
dihydrobiaryls
in benzene;
phenylazotriphenylmethane
phenyl
involve
peroxides
in the arylation
deuterated
it
with
in essential
criteria
in the dispropcrtionation
of
not
to a much lesser
decomposing
sition
arylation
differs
essential
though
to the
aromatic
peroxides.
Three
and,
that does
and therefore
diaroyl
free-radical
the decomposition apparent
isotope
of nitrosoacetanilides
of diaroyl effects,
peroxides
4 these
effects
in benzene-d (I.E.)
and arylazotriphenylmethanes
One of us (0,s.) has independently tories of the University of Tokyo, analysis.
involves
in the decompoin benzene-d
confirmed this result in the laboraTokyo, Japan,by isotope dilution
are
Mechanisms
No.17
very
small,
well
of
within
aromatic
free-radical
substitution
to be expected
the range
of
751
secondary
isotope
effects:
While
appreciable
sition
of
benzoyl
aroyl
peroxides
peroxide,
4 0.53
dideuterated anilide
amounts of dideuterated
biaryl
(0.0-0.20
per cent),
in benzene-g
of
mole per cent),
the eight
per
studied,
for
(e.g.
phenyl)
when N-nitrosoacetanilides
instead
of
the expense
of
~a.
0.15
M to 85 per cent
Such increases with
higher-order
peroxides
in yield side
in benzene
mole per cent)
was found
by Hey8 that for
solution.
the yield
cent
at 0.015
strongly reactions.
results
increase
for
M) occurs suggest
with
in low yields
of
7 No explanation is apparent for the occurrence material in the other four cases. 8 E.C. Sutterworth and D.H. Hey, J. Chem. Sot.
of
(0.025
biaryl
(from
M)
yield
mainly,
process
decomposition arylbenzene of
in
is
at
of
55 per cent
at
phenylazotriphenylmethane.
a first-order
In contrast,
in fact,
e-chlorobi-
increased
in yield
and e-
from 50 to 91
in dilute
This
mole
at a11.7
biphenyl,
to 80 per
are decomposed
A similar
(0.23
were much less;
no d2 material
M)
e-chloro-
the amounts of
peroxide),
- ArH from ArN(NO)COCH3 - and,
tars.
for
of e-methoxy-N-nitrosoacet-
cent)
from 44.5
(0.25
hydrocarbon
nitrogen-containing
e-toluyl
to 91 per cent
e-methoxybiphenyl,
in concentrated
per
the report
from 66.5
mole per cent
(0.0-0.09
(0.0
we have confirmed
sharply
cent
cases
in the decompo-
e-methyl-N-nitrosoacetanilide
e-chloro-N-nitrosoacetanilide
Also, climbs
for
were found
0.39
in the decomposition
chlorophenylazotriphenylmethane four
(e.g.
mole per cent
found
biaryls
small
116 (1938).
competing of diaroyl
(<50 per cent) amounts of d2
in
Mechanisms
752
either
concentrated
phenyls
and
a major
in
and
little
any
acetate
before
benzene or
aromatic
solution.
in
acetic
no methane
acid
and
formed a chance
and
coworkers
must to
In dilute formed
the
decomposition
are
abstract
undergo
as
dihydrobi-
by-products.5 of nitrosoacet-
1 mole/mole
dioxide
No.17
solution,
are
(nearly
carbon
substitution
of
formed.
hydrogen
This
with
decarboxylation,
nitroso
compound),
suggests
extreme known
to
that
rapidity occur
with
ease.9
arylation
acetates,
with
further
free
aryl
reaction (Ar.)
peroxides
of
reaction
the
of
in as
difference
in
the
tively
stable
before
they
cals,
concerted radicals
fact
that
gradually
rate-determining
rearrangement
and
in
benzoyl
of
radicals
which
carbon
decomposition
Two possibilities
suggest Prosen
then
and
to
the
or
themselves J.
the
Liebios
from
Chem.
Phvs.
Ann.
5&,
137
spoken
in to
and our the
each
view rela-
other
phenyl
radi-
undergo
reactive
a
phenyl
radicals.
attack
L. Krause, Liebiqs Ann. 524, 157, Amer. Chem. Sot. a, 144~1951). G. Horeld,
rise
reactive
very
of
hand
other
triphenylmethyl
for
involve
The reason
phenylazotriphenylmethane
acetate
and M. Szwarc,
on the
the
that
already
on one
away
give
immediately
and
not
have
gives
diffuse
dioxide
producing nitrogen
peroxide
in
decomposition
peroxide 12
benzoyl
doubt
mechanism”.
phenylazotriphenylmethane homolysis
any does
the
Horeld”
by a “cryptoradical
step
w-diazo-
beyond
benzene
encountered
between
to
prove with
Huisgen
benzenediazoacetate
9 L. Jaffe, E.J. 10 R. Huisgen and D.F. DeTar, J. 11 R. Huisgen and 12 R. Huisgen and the “cryptoradical that the Ph;$J* may, however,
the
results
type
324
behavior
lose
with
that is
the
proceeding
benzoate
along
shown
diazoacetates
benzene.
and
whereas
these of
in
nitrosoacetanilide lies
have
The present
3’
radicals
diaroyl this
10
nitrosoacetanilides
Ar-N=N-OCOCH
the
for
is
have
Huisgen the
dilute
by-product
radicals
they
great
or
free-radical
tetrahydroquaterphenyls
Finally, anilides
of
of 22,
171
phenyl 416
(1951).
and
(1957). See
also
(1949).
H. Nakaten, Liebiqs Ann. 186, 70 (1954) have rejected mechanism” for Ph-N=NCPh3 on the basis of the finding radical could be intercepted by iodine or NO. This finding be explainable on the basis of a cage effect (see below).
Mechanisms
No.17
acetate
(or acid
before
the bonds
for
(or
for
to nitrogen
several
acetates tively
for
trans
picture,
radicals
respectively)
molecule.
This
perhaps
reaction. reaction
Iodine
13
with
radical
the
a very
corner
the acetate
in the walls
the aryldiazo-
of
of
and
are in the relahave to
a concerted
attack.
a diffusion
controlled
and acetate
(or
tri-
and in juxtaposition and hydrogen
activation
energy
to zero,
of
radical for
the ad-
a postulate
energy
for
with
of
which this
the subsequent
acetate
has time
ab-
benzene
exothermicity
radical
may compete
iodine
in that
low activation
concentration
of
by Huisgen
a solvent
the large
account
reaction
of
close
such
substitution
intervention
radicals
arylcyclohexadienyl before
favor
properly
to invoke
that
and
which occurs
the “radical”
(by addition
the is
It
molecules
is
the nearest
in view of
immediately,
13
react
to benzene
requires
not
simultaneously
not unreasonable also
attack
and one would probably
phenyl
mechanism demands that
and NO in large
the benzene
10
are generated
of the resulting
must follow
in which
biphenyl
of nitrosoacetanilides
in our view,
and simultaneously
of a phenyl
explain
753
We do not
does
of
interconversion
14
reaction
straction,
dition
it
difficulty
configuration
A more likely
and then rapidly
broken.
that
not
a geometric
cis-trans
phenylmethyl)
is
also
a rapid
(“cage-effect*)
does
by rearrangement
unfavorable
postulate
it
to give
a concerted
the phenylazotriphenylmethane is
generated
is
characteristic
pattern’
There
Nakaten12.
tie
One is
substitution
benzene
are completely
reasons.
More seriously,
or NO observed
aromatic
on substrate
triphenylmethane).
the substitution
reaction.
free-radical
triphenylmethyl)
acetic
a picture
of
which
to decompose.
the caged
radicals
with
the cage.
However this is possible as suggested by the results H. Nakaten, Liebios Ann. fish, 84 (1954).
of R. Huisgen
and
l4 C.S. Rondestvedt and H.S. Blanchard, J. Oro. Chem. a, 229 (1956). These authors suggested a cage-effect also for the maroy peroxide reaction where it has now been shown not to operate (refs. 3,4). See also G.S. Hammond, J.T. Rudesill and F.J. Medic, J. Amer. Cbem , . S o._, c P 3929 (1951).
WECHANISMSOF FREE-RADICALAROMATIC SUBSTITUTION E.L. Eliel, M. Eberhardt and 0. Simamura Department of Chemistry and RadiationLaboratorp University of Notre Dame, Notre Dame, Indiana
S.
Meyerson
Research and DevelopmentDepartment,American Oil Company, Whiting, Indiana (Received26 May 1962) 1 SINCE Hey's and Waters' studies on free-radicalaromatic substitution, such diverse reactions as the Gomberg-Bachmannreaction and the decompoarylazotriphenylmethanes and diaroyl sition of nitrosoacetanilides, peroxides in aromatic substrateshave been widely assumed to proceed by the same general mechanism once the substitutingaryl radicals are gener2 ated.
Work in DeTar's laboratory3and ourslcy5has shown that an important
contributingstep in the free-radicalarylationof benzene by diaroyl peroxides is disproportionationr
* Supported under contractwith the U.S. Atomic Energy Commission. 1 D.F. Hey, J. Chem. Sot. 1966 (1934);D.H. Hey and W.A. Waters, Chem. Rev. 2 a, 169 (1937). D.R. Augood and G.H. Williams,Chem. Rev. 12, 123 (1957);G.H. Williams, HomolvticAromatic SubstitutionChap. 4. Pergamon Press, New York (1960). See, however, H. Zollinger,&iazo and Azo Chemistry pp. 153-159, Interscience,New York (1961), for a contrary view. 3 D.F. DeTar and R.A.J. Long, J. Amer. Chem. Sot. @, 4742 (1958);D.F. DeTar, Abstracts.SeventeenthNational Oraanic ChemistrySvmoosium American Chem. Sot.. Bloominaton.Indiana, 1961, p. 59. 4 E.L. Eliel, S. Meyerson, Z. Welvart and S.H. Wilen, J. Amer. Chem. SOC.
'B, 2936 (1960). _' M. Eberhardt and E.L. Eliel, J. Ora. Chem. 2, 749
2289 (1962).
Mechanisms
750
We have now found
of
evidence
arylazotriphenylmethanes mediates
peroxides
are:
in the
(a)
diaroyl
arylation
arylbenzene
biaryl-A2
of
(I)
for
formation
of
formed4
arylation
extent,
- due,
and
(II)
as inter-
from arylation
with
(E.
could
0.15
of nitrosoacetanilide
survived
in dilute
(0.02
with
be detected (~a.
reaction.
(cf.
ref.
appearance oxidation
of
the
of of di-
these
criteria
nitrosoacetanilides
0.015
hi) solution
and with
of
in either
after
decompo-
in benzene.
solutions,
In control
3)
effect
discrimination
by gas chromatography
in the decomposition
M) solution
of
analog.
was added to the dilute
found
of
M)
content
isotopic (c)
(0.02
isotope
or phenylazotriphenylmethane
the arylation
was readily
to
diaroyl
M) solutions
We have now applied
e-chloro
M) or dilute
(0.2
as a result
benzene-d
and its
in dilute3
from the deuterium
radicals;
species.
with
an apparent
in part,
benzene-&
(II)
arylation
(II)
(b)
of hydrobiaryl of
of
in concentrated5
at least
of benzene.and
When dihydrobiphenyl
about
75 per cent
experiments, benzoyl
6
dihydrobi-
peroxide
and even at concentrations
in benzene as high
M. 5
Whereas appreciable
6
fashion
dihydrobiaryls
as computed
dihydrobiaryl
concentrated
sition
No.17
nitrosoacetanilides
the mechanism
benzene-d
No dihydrobiphenyl
as 0.2
substitution
dihydrobiaryls
in benzene;
phenylazotriphenylmethane
phenyl
involve
peroxides
in the arylation
deuterated
it
with
in essential
criteria
in the dispropcrtionation
of
not
to a much lesser
decomposing
sition
arylation
differs
essential
though
to the
aromatic
peroxides.
Three
and,
that does
and therefore
diaroyl
free-radical
the decomposition apparent
isotope
of nitrosoacetanilides
of diaroyl effects,
peroxides
4 these
effects
in benzene-d (I.E.)
and arylazotriphenylmethanes
One of us (0,s.) has independently tories of the University of Tokyo, analysis.
involves
in the decompoin benzene-d
confirmed this result in the laboraTokyo, Japan,by isotope dilution
are
Mechanisms
No.17
very
small,
well
of
within
aromatic
free-radical
substitution
to be expected
the range
of
751
secondary
isotope
effects:
While
appreciable
sition
of
benzoyl
aroyl
peroxides
peroxide,
4 0.53
dideuterated anilide
amounts of dideuterated
biaryl
(0.0-0.20
per cent),
in benzene-g
of
mole per cent),
the eight
per
studied,
for
(e.g.
phenyl)
when N-nitrosoacetanilides
instead
of
the expense
of
~a.
0.15
M to 85 per cent
Such increases with
higher-order
peroxides
in yield side
in benzene
mole per cent)
was found
by Hey8 that for
solution.
the yield
cent
at 0.015
strongly reactions.
results
increase
for
M) occurs suggest
with
in low yields
of
7 No explanation is apparent for the occurrence material in the other four cases. 8 E.C. Sutterworth and D.H. Hey, J. Chem. Sot.
of
(0.025
biaryl
(from
M)
yield
mainly,
process
decomposition arylbenzene of
in
is
at
of
55 per cent
at
phenylazotriphenylmethane.
a first-order
In contrast,
in fact,
e-chlorobi-
increased
in yield
and e-
from 50 to 91
in dilute
This
mole
at a11.7
biphenyl,
to 80 per
are decomposed
A similar
(0.23
were much less;
no d2 material
M)
e-chloro-
the amounts of
peroxide),
- ArH from ArN(NO)COCH3 - and,
tars.
for
of e-methoxy-N-nitrosoacet-
cent)
from 44.5
(0.25
hydrocarbon
nitrogen-containing
e-toluyl
to 91 per cent
e-methoxybiphenyl,
in concentrated
per
the report
from 66.5
mole per cent
(0.0-0.09
(0.0
we have confirmed
sharply
cent
cases
in the decompo-
e-methyl-N-nitrosoacetanilide
e-chloro-N-nitrosoacetanilide
Also, climbs
for
were found
0.39
in the decomposition
chlorophenylazotriphenylmethane four
(e.g.
mole per cent
found
biaryls
small
116 (1938).
competing of diaroyl
(<50 per cent) amounts of d2
in
Mechanisms
752
either
concentrated
phenyls
and
a major
in
and
little
any
acetate
before
benzene or
aromatic
solution.
in
acetic
no methane
acid
and
formed a chance
and
coworkers
must to
In dilute formed
the
decomposition
are
abstract
undergo
as
dihydrobi-
by-products.5 of nitrosoacet-
1 mole/mole
dioxide
No.17
solution,
are
(nearly
carbon
substitution
of
formed.
hydrogen
This
with
decarboxylation,
nitroso
compound),
suggests
extreme known
to
that
rapidity occur
with
ease.9
arylation
acetates,
with
further
free
aryl
reaction (Ar.)
peroxides
of
reaction
the
of
in as
difference
in
the
tively
stable
before
they
cals,
concerted radicals
fact
that
gradually
rate-determining
rearrangement
and
in
benzoyl
of
radicals
which
carbon
decomposition
Two possibilities
suggest Prosen
then
and
to
the
or
themselves J.
the
Liebios
from
Chem.
Phvs.
Ann.
5&,
137
spoken
in to
and our the
each
view rela-
other
phenyl
radi-
undergo
reactive
a
phenyl
radicals.
attack
L. Krause, Liebiqs Ann. 524, 157, Amer. Chem. Sot. a, 144~1951). G. Horeld,
rise
reactive
very
of
hand
other
triphenylmethyl
for
involve
The reason
phenylazotriphenylmethane
acetate
and M. Szwarc,
on the
the
that
already
on one
away
give
immediately
and
not
have
gives
diffuse
dioxide
producing nitrogen
peroxide
in
decomposition
peroxide 12
benzoyl
doubt
mechanism”.
phenylazotriphenylmethane homolysis
any does
the
Horeld”
by a “cryptoradical
step
w-diazo-
beyond
benzene
encountered
between
to
prove with
Huisgen
benzenediazoacetate
9 L. Jaffe, E.J. 10 R. Huisgen and D.F. DeTar, J. 11 R. Huisgen and 12 R. Huisgen and the “cryptoradical that the Ph;$J* may, however,
the
results
type
324
behavior
lose
with
that is
the
proceeding
benzoate
along
shown
diazoacetates
benzene.
and
whereas
these of
in
nitrosoacetanilide lies
have
The present
3’
radicals
diaroyl this
10
nitrosoacetanilides
Ar-N=N-OCOCH
the
for
is
have
Huisgen the
dilute
by-product
radicals
they
great
or
free-radical
tetrahydroquaterphenyls
Finally, anilides
of
of 22,
171
phenyl 416
(1951).
and
(1957). See
also
(1949).
H. Nakaten, Liebiqs Ann. 186, 70 (1954) have rejected mechanism” for Ph-N=NCPh3 on the basis of the finding radical could be intercepted by iodine or NO. This finding be explainable on the basis of a cage effect (see below).
Mechanisms
No.17
acetate
(or acid
before
the bonds
for
(or
for
to nitrogen
several
acetates tively
for
trans
picture,
radicals
respectively)
molecule.
This
perhaps
reaction. reaction
Iodine
13
with
radical
the
a very
corner
the acetate
in the walls
the aryldiazo-
of
of
and
are in the relahave to
a concerted
attack.
a diffusion
controlled
and acetate
(or
tri-
and in juxtaposition and hydrogen
activation
energy
to zero,
of
radical for
the ad-
a postulate
energy
for
with
of
which this
the subsequent
acetate
has time
ab-
benzene
exothermicity
radical
may compete
iodine
in that
low activation
concentration
of
by Huisgen
a solvent
the large
account
reaction
of
close
such
substitution
intervention
radicals
arylcyclohexadienyl before
favor
properly
to invoke
that
and
which occurs
the “radical”
(by addition
the is
It
molecules
is
the nearest
in view of
immediately,
13
react
to benzene
requires
not
simultaneously
not unreasonable also
attack
and one would probably
phenyl
mechanism demands that
and NO in large
the benzene
10
are generated
of the resulting
must follow
in which
biphenyl
of nitrosoacetanilides
in our view,
and simultaneously
of a phenyl
explain
753
We do not
does
of
interconversion
14
reaction
straction,
dition
it
difficulty
configuration
A more likely
and then rapidly
broken.
that
not
a geometric
cis-trans
phenylmethyl)
is
also
a rapid
(“cage-effect*)
does
by rearrangement
unfavorable
postulate
it
to give
a concerted
the phenylazotriphenylmethane is
generated
is
characteristic
pattern’
There
Nakaten12.
tie
One is
substitution
benzene
are completely
reasons.
More seriously,
or NO observed
aromatic
on substrate
triphenylmethane).
the substitution
reaction.
free-radical
triphenylmethyl)
acetic
a picture
of
which
to decompose.
the caged
radicals
with
the cage.
However this is possible as suggested by the results H. Nakaten, Liebios Ann. fish, 84 (1954).
of R. Huisgen
and
l4 C.S. Rondestvedt and H.S. Blanchard, J. Oro. Chem. a, 229 (1956). These authors suggested a cage-effect also for the maroy peroxide reaction where it has now been shown not to operate (refs. 3,4). See also G.S. Hammond, J.T. Rudesill and F.J. Medic, J. Amer. Cbem , . S o._, c P 3929 (1951).