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Selectivity in electrophilic attack on ambidental aromatic ions: synthesis of 2,2′-dihydroxytriphenylmetanes
PergamonPress. Printed in Great Britain.
TetrahedronLettersNo. 43, pp.3969 - 3972, 1971.
SELECTIVITY
IN ELECTROPHILIC
ATTACK ON AMBIDENTAL
AROMATIC
IONS : SYNTHESIS OF
2,2'-DIHYDROXYTRIPHENYLMETANES G. Casiraghi,
G. Casnati and G. Sartori
Istituto di Chimica Organica, (Receivedin lE 10 August 1971;
In contrast to what is generally under particular
Universita
di Parma, Italy
acceptedfor publication22 September1971)
reaction conditions,
accepted', we have recently proved* that,
the reactivity
ion pair, can be enhanced by increasing
of an ambident system in an
the coordinating
power3 of the cationic
counterion. Now, we have studied the reactivity several electrophilic
In the present work we report with benzaldehyde (II) previously
form the 2,2'-dihydroxyderivatives almost completely unknown.
A selective
attack at theortho position Benzyl alcohol
reacts quantitatively
only one of the possible R
the reaction of phenoxymagnesium
which
in all the cases studied516. intermediate,
of various ambident systems with
reagents4.
to the phenoxy group was observed
(III),the hypothetical
with the aryloxymagnesium
R
MgX
R
R'
R*
R3
to form (II).
H
R2
(11)
(III)
(1)
reaction
halides
isomers: the 2,2'-dihydroxytriphenilmetanes R
MgX
halides
of triphenilmethane
R
R1
R*
R3
H
Me
H
Ia
IIa
H
H
H
H
Ih
IIh
Me
Ib
IIb
Me
H
H
H
Ii
Iii
Pr' H
H
Me
Ic
IIc
H
H
Me
H
I1
II1
Me
H
H
Pi?
Id
IId
Pi? H
H
H
I,
IIm
H
H
OMe H
Ie
IIe
H
Pri H
In
IIn
If
IIf
But H
H
IO
II0
I g
II
H
BU
g
H
H
H tH
3969
C4H4 H
H C4H4
H H
3970
No. 43 Reaction of aryloxymaqnesium Phenol
Product
bromides with bensaldehyde'
gtt
ueld
0
Jn.w.
c
&&ttt
I1a
53
128-129
6.10
'b
*Ib
74
127-128
5.88
Ic
I1c
80
IId
100
I1e
93
Ia
Id Ie If I q 'h I. 1
100
I1f II 4 I1h Iii
I1
'Irn
In
IIn
IO
5.90 5.85
oil
5.90
126-128
5.70
79
oil
6.00
69
107-108
5.88
87
112-113
5.88
oil
5.70
78
130-132
5.90
100
172-174
5-75
100
182-183
5.70
5
I11
Irn
oil 103-104
I10
'Refluxed in benzene for 20 hr; mole ratios ArOMqBr : C6H5CH0 = 1 : 1. The remainder of the 100% is constituted of non reacted phenol.
tt
'++Chemical
shift of the methinic
The importance coordinating
at 60 MC in CDC13.
in these reactions of the acid character and of the
power of the cation is in agreement with the lack of reactivity of
the Na+ , Li+ and Mq++ phenolic corresponding
proton registered
magnesium
salts, compared to
the high reactivity
of the
halides. Table 1
Cation effect on the reaction of same phenol salts with bensaldehydet Reagent Phenol*
Cation
Phenol reacted %
H+§, Na+, Li+, Mq'+
Phenol*
MqBr+
o-Tertbutylphenol'
Na+, Li+
o-tertbutylphenol'
MqBr+
Resorcinol'
H+, Na+
Resorcinol'
MqBr+
0.0 53 0.0 80 trace 68
t All the reactions have been conducted in refluxinq benzene. Mole ratios ArOMqBr : C6H5CH0 = 1 : 1. * Reaction time: 20 hr. 5 Also in the presence of stoichiometric ?I Reaction time: 3 hr.
It is quite significant
quantities
of MqBr2 and MqC12.
the fact that the ortho-disubstituted
No. 43
2,6-dimethylphenoxymagnesium stituted isomer
bromide does not react, while the ortho,para-disub-
(Ih) is highly reactive.
These data support the hypothesis an
electrophilic
of a reaction mechanism
which involves
attack, catalysed by a Lewis acid coordinated
reagent and with the phenoxy attack is selective
both with the
function of the substrate. For this reason the
towards the ortho-position.
The lack of reactivity
of phenol with benzaldehyde
in the presence of
MgCl2 and MgBr2, shows at the same time the importance of the basicity of the substrate. This strong sensitivity of the reaction to electronic factors is shown by the inehiia of chlorophenols observed
in the case of particularly
and by the increased basic substrates,
The influence of the catalytic
action of the counterion7,
also clearly shown in this case: both resorcinol less reactive
than the corresponding
From a preliminary also react selectively corresponding
magnesium
acetals and a,6-unsaturated
bromide.(Tab.
function by aliphatic
and distinct
to the phenoxy without
lR. Gompper, Angew.
medium.
power can be modified
G. Casnati
new
of attack in the ortho-position
of reaction with basic substrates of these processes.
and notes
Chimica e lndu4tkia 49, 172 (1967). by verying
and A. Pochini,
the nature of the reaction
Chimica e lndustcia 49, 630 (1967).
on the phenol reacted.
isolated by simple crystallisation
reaction mixture distillation)
these reactions present a mechanism
2.
'The yields are almost quantitative 6The compounds
to
Chem. Int. Ed. 3, 560 (1964).
See reference
4B. Cardillo,
are the first proce-
of the catalyst are the main peculiarities
G. Casnati and A. Pochini,
3The coordinating
their
in the ortho-position
at the same ti.me a
it: the high selectivity
References
2B Cardillo,
halides
and aromatic aldehydes8.
function, and the possibility
inactivation
reactions
attacks selectively
type9 , they represent
class within
1).
aldehydes.
from a general point of view
of the Friedel-Crafts
is
with the aliphatic aldehydes,
From a synthetic point of view, these new
Although
however,
and its sodium salt are much
study it was found that the aryloxymagnesium
in the ortho-position
dures to bring about electrophilic a phenoxy
reactivity
such as resorcinols.
(or distillation)
from the
(after removal of the non reacted phenol and aldehydes by steam
give analytical data and spectrographs
agreement with the proposed
structure:
which are completely
the ortho-substitution
in
was determined
on the basis of the n.m.r. spectra, and by comparison with the para-substituted derivatives.
In the n.m.r. spectrum the chemical shift of the methinic
in the 2,2'-dihydroxysubstituted -dihydroxysubstituted substituted
derivatives
derivatives
derivatives
is at 5.70-6.10,
at 5.30-5.50,
at 5.50-5.606.
proton
in the 4,4'-
and in the 2,4'-dihydroxy-
3972
No. 43
'The cationic counterion is not necessarily MgBr'. A Schlenk type or associations equilibria could occur in the system. sThe reactions of aldehydes and ketones with phenols, catalysed by protic or Lewis acids, form mainly a mixture of di- or triphenylmethane derivatives in and aeLated which products from the para attack prevail. G. Olah, fhiede.t-Cha&tb hcdct.ionb, vol. II, part 1, page 597 (1964), Interscience Publ. gThese processes are to be ascribed to a Friedel-Crafts reaction: an electrophilic attack on a basic substrate catalysed by a Lewis acid occurs.
TetrahedronLettersNo. 43, pp.3969 - 3972, 1971.
SELECTIVITY
IN ELECTROPHILIC
ATTACK ON AMBIDENTAL
AROMATIC
IONS : SYNTHESIS OF
2,2'-DIHYDROXYTRIPHENYLMETANES G. Casiraghi,
G. Casnati and G. Sartori
Istituto di Chimica Organica, (Receivedin lE 10 August 1971;
In contrast to what is generally under particular
Universita
di Parma, Italy
acceptedfor publication22 September1971)
reaction conditions,
accepted', we have recently proved* that,
the reactivity
ion pair, can be enhanced by increasing
of an ambident system in an
the coordinating
power3 of the cationic
counterion. Now, we have studied the reactivity several electrophilic
In the present work we report with benzaldehyde (II) previously
form the 2,2'-dihydroxyderivatives almost completely unknown.
A selective
attack at theortho position Benzyl alcohol
reacts quantitatively
only one of the possible R
the reaction of phenoxymagnesium
which
in all the cases studied516. intermediate,
of various ambident systems with
reagents4.
to the phenoxy group was observed
(III),the hypothetical
with the aryloxymagnesium
R
MgX
R
R'
R*
R3
to form (II).
H
R2
(11)
(III)
(1)
reaction
halides
isomers: the 2,2'-dihydroxytriphenilmetanes R
MgX
halides
of triphenilmethane
R
R1
R*
R3
H
Me
H
Ia
IIa
H
H
H
H
Ih
IIh
Me
Ib
IIb
Me
H
H
H
Ii
Iii
Pr' H
H
Me
Ic
IIc
H
H
Me
H
I1
II1
Me
H
H
Pi?
Id
IId
Pi? H
H
H
I,
IIm
H
H
OMe H
Ie
IIe
H
Pri H
In
IIn
If
IIf
But H
H
IO
II0
I g
II
H
BU
g
H
H
H tH
3969
C4H4 H
H C4H4
H H
3970
No. 43 Reaction of aryloxymaqnesium Phenol
Product
bromides with bensaldehyde'
gtt
ueld
0
Jn.w.
c
&&ttt
I1a
53
128-129
6.10
'b
*Ib
74
127-128
5.88
Ic
I1c
80
IId
100
I1e
93
Ia
Id Ie If I q 'h I. 1
100
I1f II 4 I1h Iii
I1
'Irn
In
IIn
IO
5.90 5.85
oil
5.90
126-128
5.70
79
oil
6.00
69
107-108
5.88
87
112-113
5.88
oil
5.70
78
130-132
5.90
100
172-174
5-75
100
182-183
5.70
5
I11
Irn
oil 103-104
I10
'Refluxed in benzene for 20 hr; mole ratios ArOMqBr : C6H5CH0 = 1 : 1. The remainder of the 100% is constituted of non reacted phenol.
tt
'++Chemical
shift of the methinic
The importance coordinating
at 60 MC in CDC13.
in these reactions of the acid character and of the
power of the cation is in agreement with the lack of reactivity of
the Na+ , Li+ and Mq++ phenolic corresponding
proton registered
magnesium
salts, compared to
the high reactivity
of the
halides. Table 1
Cation effect on the reaction of same phenol salts with bensaldehydet Reagent Phenol*
Cation
Phenol reacted %
H+§, Na+, Li+, Mq'+
Phenol*
MqBr+
o-Tertbutylphenol'
Na+, Li+
o-tertbutylphenol'
MqBr+
Resorcinol'
H+, Na+
Resorcinol'
MqBr+
0.0 53 0.0 80 trace 68
t All the reactions have been conducted in refluxinq benzene. Mole ratios ArOMqBr : C6H5CH0 = 1 : 1. * Reaction time: 20 hr. 5 Also in the presence of stoichiometric ?I Reaction time: 3 hr.
It is quite significant
quantities
of MqBr2 and MqC12.
the fact that the ortho-disubstituted
No. 43
2,6-dimethylphenoxymagnesium stituted isomer
bromide does not react, while the ortho,para-disub-
(Ih) is highly reactive.
These data support the hypothesis an
electrophilic
of a reaction mechanism
which involves
attack, catalysed by a Lewis acid coordinated
reagent and with the phenoxy attack is selective
both with the
function of the substrate. For this reason the
towards the ortho-position.
The lack of reactivity
of phenol with benzaldehyde
in the presence of
MgCl2 and MgBr2, shows at the same time the importance of the basicity of the substrate. This strong sensitivity of the reaction to electronic factors is shown by the inehiia of chlorophenols observed
in the case of particularly
and by the increased basic substrates,
The influence of the catalytic
action of the counterion7,
also clearly shown in this case: both resorcinol less reactive
than the corresponding
From a preliminary also react selectively corresponding
magnesium
acetals and a,6-unsaturated
bromide.(Tab.
function by aliphatic
and distinct
to the phenoxy without
lR. Gompper, Angew.
medium.
power can be modified
G. Casnati
new
of attack in the ortho-position
of reaction with basic substrates of these processes.
and notes
Chimica e lndu4tkia 49, 172 (1967). by verying
and A. Pochini,
the nature of the reaction
Chimica e lndustcia 49, 630 (1967).
on the phenol reacted.
isolated by simple crystallisation
reaction mixture distillation)
these reactions present a mechanism
2.
'The yields are almost quantitative 6The compounds
to
Chem. Int. Ed. 3, 560 (1964).
See reference
4B. Cardillo,
are the first proce-
of the catalyst are the main peculiarities
G. Casnati and A. Pochini,
3The coordinating
their
in the ortho-position
at the same ti.me a
it: the high selectivity
References
2B Cardillo,
halides
and aromatic aldehydes8.
function, and the possibility
inactivation
reactions
attacks selectively
type9 , they represent
class within
1).
aldehydes.
from a general point of view
of the Friedel-Crafts
is
with the aliphatic aldehydes,
From a synthetic point of view, these new
Although
however,
and its sodium salt are much
study it was found that the aryloxymagnesium
in the ortho-position
dures to bring about electrophilic a phenoxy
reactivity
such as resorcinols.
(or distillation)
from the
(after removal of the non reacted phenol and aldehydes by steam
give analytical data and spectrographs
agreement with the proposed
structure:
which are completely
the ortho-substitution
in
was determined
on the basis of the n.m.r. spectra, and by comparison with the para-substituted derivatives.
In the n.m.r. spectrum the chemical shift of the methinic
in the 2,2'-dihydroxysubstituted -dihydroxysubstituted substituted
derivatives
derivatives
derivatives
is at 5.70-6.10,
at 5.30-5.50,
at 5.50-5.606.
proton
in the 4,4'-
and in the 2,4'-dihydroxy-
3972
No. 43
'The cationic counterion is not necessarily MgBr'. A Schlenk type or associations equilibria could occur in the system. sThe reactions of aldehydes and ketones with phenols, catalysed by protic or Lewis acids, form mainly a mixture of di- or triphenylmethane derivatives in and aeLated which products from the para attack prevail. G. Olah, fhiede.t-Cha&tb hcdct.ionb, vol. II, part 1, page 597 (1964), Interscience Publ. gThese processes are to be ascribed to a Friedel-Crafts reaction: an electrophilic attack on a basic substrate catalysed by a Lewis acid occurs.