- Email: [email protected]
The reaction of superoxide anion radical with electron poor olefins
Tetrahedron Letters No. 52, PP 4631 - 4634, 1977. Pergamon Press. Printed in Great Britain.
THE REACTION
OF SUPEROXIDE
Aryeh A. Frimer*, *Department t
Department
ANION
Ionel Rosenthal+
of Chemistry,
of Organic
RADICAL WITH ELECTRON
Chemistry,
Bar-Ilan
POOR OLEFINS
and Shmaryahu
Has*
University,
Ramat-Gan,
Institute
of Science,
The Weismann
Israel Rehovot,
Israel
(Received in UK 19 October 1977; accepted for publication 3 November 1977) The intermediacy of superoxide anion radical, 0 - , has been suggested different
metabolic
processes
which
involve oxidation
to date has been carried out in aqueous but rather
its conjugate
are more likely of potassium O2
superoxide
in aprotic
anion radical
expected
the presence Indeed,we
species.
does not normally
transfer.
organic
done
solvents
The complexation
generation
of 02-02-
of "naked"
acceptors
3
Considering,
however,
and 02- -H202 at neutral pH are -0.33 and +0.94V respect-
feature of this radical
of electron
react with olefins.
anion is the ability
to act as a reductant
in
and as an oxidant
in the presence of electron donors. 5 chalcones and tetracyclone3, through a
have shown that 0 - oxidatively cleaves 2 involves initial electron transfer
nitrophenols.
Furthermore,
the unambiguous
process which probably we reported6
however,
it is likely that not 02-
active sites in many enzymes.
with crown ethersI permits
that the redox potentials an
the hydrophobic
for several
the research,
solvents.
Superoxide
ivelyl,
Mostof
and protic media in which
acid HO; is the reactive
to resemble
l2 .
to the enone moiety.
Similarly
that 0 - can react with substituted nitrobenzenes to produce the corresponding 2 The nucleophilic aromatic substitution also seems to proceed via an electron
We now report
the reaction
of 0 - with several electron 2
poor cyano and nitro-
olefins. In a typical experiment,1 20 ml of dry benzene and showed
were
mm01
stirred overnight
The aqueous
extracts
were acidified
and the identity The results
substituted
acetophenones
extracted
subsequently
removed
and 4 mmol
of K02 in
was followed by TLC The solu-
material.
with saturated
NaHC03
into ether.
The ether layer
under vacuum.
The residue was
and the acids extracted
were
ascertained
by spectral
followed by TIC and for compounds
could be clearly observed
but eventually
and acetophenones,
.
The reaction
of the starting
mixture
and ratio of the product(s)
the reactions
stages of the reaction bensaldehydes
of 18-crown-6
data
(MS and
are shown in the Table.
As noted above sponding
in the dark.
with cont. HCl and the reaction
was dried over MgS04 and the solvent
NMR).
2 mm01
in nearly all cases the total disappearance
tion was acidified
weighed
of olefin,
disappeared.
corresponding
the corre-
in each case in the initial
In control
to compounds
Va-d
experiments
the substituted
IV and V respectively,
were
oxidized by 02- and yielded the corresponding benzoic acids. Atropic acid' proved inert to 1 Treatment of IVa and Va with KOH /crown ether gave only small amounts (
4631
No.
4632
Table Compound*
Product
$ I -
II -
'NO
2
'C=O HO'
'NO2
+‘\C=C' H'
(85%)
H
0C02H
'NO
(85%)
2
PR-CgHq
‘C=O RI'
v
(84%)
0
$\C/ H'
III -
6, c=xl 0’
\C=c/No2
0'
(yield) **
CR’ = H&H
E-R-CSH4
3
1
R-CSH4C02H
CN
'DC& H)
v
a:
R-H
70%
b:
R = NO
74%
C:
R = Br
d:
R=OCB
2
90% 80%
3
EyjH4\
R-C8H4C02H
CN
3
R-C6H4-C-C02H
C=C’
H3C' a:
R=H
81%
10%
b:
R = CH
50%
25%
35%
35%
C:
3 R=OCii3
d:
R = Br
@:OH
'LX' Et' 'CN
*The olefins
were prepared
**For compounds phenyl
_*
35% +
CN
$ -VI
VII
'CN
to known
I-III, yields were determined
as standard.
isolated
according
residue
literature by VPC
For -IV-VI the total yields
(see text).
(87%)
procedures'
(10% SE-30 WBMCS)
The ratio of benzoic
to atropic
acids8were
termined by NMR integration. t Substantial * Presence
amounts
of an unidentified
using bi-
are based on the weight
polymeric
of this acid in a low yield is indicated
material by MS.
is formed
of the de-
52
NO. 52
4633
10,ll is not observed products after 24 hours of reaction. Hence base catalyzed autoxidation 18 - labeled benzophenone was observed involved to any substantial extent. Less than 10% 0 12 16 in the oxidative cleavage of L in the mass spectrum of the product when lCOz18replaced KO 2 Attempts were made to detect via ESR, immediately following the mixing of K02 and olefin, the paramagnetic specia involved in this reaction. A well resolved spectrum of the corresponding anion radical could be recorded for -I (aN=2.84G, a =2.50G, a2(lj=l.O5G. l(2) a3=2.80G). The computer simulated spectrum overlapped the experimental one. Parsmagnetic specia were also detected for z
and Iw
but the poor resolution prevented identification.
The data indicates that for olefins I-VI the primary reaction is oxidative cleavage -5z of the double bond. As suggested previously , it is likely that the reaction proceeds by a preliminary electron transfer from 0 - to the electron poor double bond. The resulting 2 anion radical reactsin turn with surrounding molecular oxygen as sketched below.
Ar
Z 'c=c' R' 'Z
Ar\
.
AZ
+0-2
R=CH3,H Ar cpo <
HO'
Z
'C-Y? R'I 'Z o-t,
Ar
'c=o R'
or Et
L
Lee
(footnote 141
Z 'c-c' R'I I'Z
-
O-6 For compounds of Type 1 there is a second competing pathway which leads to substituted atropic acids. We suggest the following mechanism to rationalize their formation. The first
. Ar
Ar
CN 'C-C' CH," 'CN
/CN 'C=C CHf 'CN
'C=C' CH< 'CN
A -
J
O2
Ar
0 'C-E CH// 'CN 2
CN \C-&C:N H2C+ 1 $ Ar
-
it
o-o
C Ar -
0
-
step involves abstraction of the active allylic hydrogen. One would expect highest radical density in the allylic radical a to the ;r gives species g.
groups. Addition of oxygen to the radical A
Closure to a dioxetane and cleavage as shown to yield enone C finds pre-
.
cadent in the electrogenerated02- oxidation of benzyl
cyanide
to bensoic acid.l3
A
second electron transfer, addition of oxygen and oxidative cleavage of the cyan0 group leads to the desired product.
170. 52
4634
We have thus demonstrated poor olefins
yielding
noted above, similar
products products
that superoxide corresponding
are expected
to oxidative with electron
A report on these systems will be forthcoming
References
anion radical
readily reacts with electron
cleavage
of the double bond.
rich olefins
As
such as enol ethers.
shortly.
and Fcotnotes
1.
I. Fridovich, Act. Chem. Res., 5, 321 (1972); b) W. Bors, M. Saran, E. Lengfeldon, a) R. Sp%tt)and C. Michel, Curr.Top. Rad. Res. Quart., 2, 247 (1974); c) J.P. Henry, La Recherche, E, 370 (1975); d) I. Fridovich in Molecular Mechanisms of Oxygen Activation, 0. Hayaishi, ed., Academic Press, N.Y., (1974) p. 453.
2.
J.S. Valentine
3.
I. Rosenthal
4.
a)
5.
I. Rosenthal
6.
A. Primer
7.
and D.B. Curtis,
and A. Frimer,
J. Amer. Chem. Sot.,
Tet. Let.,
3731 (1975).
P. Muir Wood, FEBS Let., 2, 22 (1975); Israel J. Chem., 12, 891 (1974).
Olefin I
b)
Y.A. Ilan, D. Meisel
and A. Frimer,
Tet. Let.,
2805
and I. Rosenthal,
Tet. Let.,
2809 (1976).
was synthesized
9J, 224 (1975).
by the procedure
and G. Czapski,
(1976).
of E.D. Bergman
and E. Meyer,
Chem. Ber., 12 - A.I. Vogel, IV - B.B. Practical Organic Chemistry, John Wiley and Sons Inc., N.Y. c.1966) p. 717; Carson and R.W. Stoughton, J. Amer. Chem. Sot., so, 2825 (1928); 1 and E -5.T. Mowry, J. Amer. Chem. Sot., 67, 1050 (1945).
65, 446 (1932); 11 - F.G. Garbich Jr., J. Org. Chem., 21, 2322 U962);
8.
'H NMR (6, acetone-d ):VIIa-7_33(m,5H) 6.30 (d,lH,J=lHs) 5.94 (d,lH,J=lHz); VIIb-7.61 (d,ZH,J=5Hg) 7.25 (d,2H,J=SHz) 6.26 (d,lH,J=lHz) 5.90 (d,lH,J=lHz) 2.30 (s,~H);VII~-~.~O(~,ZH,J=~H~) 6.89 (d,W,J=5Hz) 6.22 (d,lH,J=lHz) 588 (d,lH,J=lHs) 3.83 (s,3H). -
9.
E.J. Skerret
and D. Woodcock,
J. Chem. Sot., 2806 (1952).
10.
a) G.A. Russel, Adv. Chem. Ser., 51, 112 (1965); 75, 174 (1968); b) G. Sosnovsky and E.H. Zaret in Organic Peroxides, Vol. I, D. Swern Ed., Wiley Interscience, N.Y. (1970) p. 517 ff.
11.
NO base catalyzed cf reference 5.
12.
I. Rosenthal,
13.
M. Tesuka, H. Hamada,
14.
Eithe f5 0 2 (functioning as an oxidizing agentlD) or starting material uence ) may serve as the electron recipients in this step.
15.
N. Kornblum,
16.
Dioxetanes are the probable intermediate in the oxidative cleavage and a-halo ketones, esters and carboxylic acids; see J.S. Fillipo, J.S. Valentine, J. Org. Chem., 41, 1078 (1976).
autooxidation
J. Labelled
was observed
Compounds
Y. Ohkatsu
in the reaction
& Radiopharmaceuticals,
and T. Osa, Denki Kagaku,
of KOH/crown
with
chalcones;
11, 317 (1976). s,
17 (1976). (in a chain seq-
Angew. Chem. Int. Ed. Eng., 14, 734 (1975). of a-keto, a-hydroxy, C. Chern and
THE REACTION
OF SUPEROXIDE
Aryeh A. Frimer*, *Department t
Department
ANION
Ionel Rosenthal+
of Chemistry,
of Organic
RADICAL WITH ELECTRON
Chemistry,
Bar-Ilan
POOR OLEFINS
and Shmaryahu
Has*
University,
Ramat-Gan,
Institute
of Science,
The Weismann
Israel Rehovot,
Israel
(Received in UK 19 October 1977; accepted for publication 3 November 1977) The intermediacy of superoxide anion radical, 0 - , has been suggested different
metabolic
processes
which
involve oxidation
to date has been carried out in aqueous but rather
its conjugate
are more likely of potassium O2
superoxide
in aprotic
anion radical
expected
the presence Indeed,we
species.
does not normally
transfer.
organic
done
solvents
The complexation
generation
of 02-02-
of "naked"
acceptors
3
Considering,
however,
and 02- -H202 at neutral pH are -0.33 and +0.94V respect-
feature of this radical
of electron
react with olefins.
anion is the ability
to act as a reductant
in
and as an oxidant
in the presence of electron donors. 5 chalcones and tetracyclone3, through a
have shown that 0 - oxidatively cleaves 2 involves initial electron transfer
nitrophenols.
Furthermore,
the unambiguous
process which probably we reported6
however,
it is likely that not 02-
active sites in many enzymes.
with crown ethersI permits
that the redox potentials an
the hydrophobic
for several
the research,
solvents.
Superoxide
ivelyl,
Mostof
and protic media in which
acid HO; is the reactive
to resemble
l2 .
to the enone moiety.
Similarly
that 0 - can react with substituted nitrobenzenes to produce the corresponding 2 The nucleophilic aromatic substitution also seems to proceed via an electron
We now report
the reaction
of 0 - with several electron 2
poor cyano and nitro-
olefins. In a typical experiment,1 20 ml of dry benzene and showed
were
mm01
stirred overnight
The aqueous
extracts
were acidified
and the identity The results
substituted
acetophenones
extracted
subsequently
removed
and 4 mmol
of K02 in
was followed by TLC The solu-
material.
with saturated
NaHC03
into ether.
The ether layer
under vacuum.
The residue was
and the acids extracted
were
ascertained
by spectral
followed by TIC and for compounds
could be clearly observed
but eventually
and acetophenones,
.
The reaction
of the starting
mixture
and ratio of the product(s)
the reactions
stages of the reaction bensaldehydes
of 18-crown-6
data
(MS and
are shown in the Table.
As noted above sponding
in the dark.
with cont. HCl and the reaction
was dried over MgS04 and the solvent
NMR).
2 mm01
in nearly all cases the total disappearance
tion was acidified
weighed
of olefin,
disappeared.
corresponding
the corre-
in each case in the initial
In control
to compounds
Va-d
experiments
the substituted
IV and V respectively,
were
oxidized by 02- and yielded the corresponding benzoic acids. Atropic acid' proved inert to 1 Treatment of IVa and Va with KOH /crown ether gave only small amounts (
4631
No.
4632
Table Compound*
Product
$ I -
II -
'NO
2
'C=O HO'
'NO2
+‘\C=C' H'
(85%)
H
0C02H
'NO
(85%)
2
PR-CgHq
‘C=O RI'
v
(84%)
0
$\C/ H'
III -
6, c=xl 0’
\C=c/No2
0'
(yield) **
CR’ = H&H
E-R-CSH4
3
1
R-CSH4C02H
CN
'DC& H)
v
a:
R-H
70%
b:
R = NO
74%
C:
R = Br
d:
R=OCB
2
90% 80%
3
EyjH4\
R-C8H4C02H
CN
3
R-C6H4-C-C02H
C=C’
H3C' a:
R=H
81%
10%
b:
R = CH
50%
25%
35%
35%
C:
3 R=OCii3
d:
R = Br
@:OH
'LX' Et' 'CN
*The olefins
were prepared
**For compounds phenyl
_*
35% +
CN
$ -VI
VII
'CN
to known
I-III, yields were determined
as standard.
isolated
according
residue
literature by VPC
For -IV-VI the total yields
(see text).
(87%)
procedures'
(10% SE-30 WBMCS)
The ratio of benzoic
to atropic
acids8were
termined by NMR integration. t Substantial * Presence
amounts
of an unidentified
using bi-
are based on the weight
polymeric
of this acid in a low yield is indicated
material by MS.
is formed
of the de-
52
NO. 52
4633
10,ll is not observed products after 24 hours of reaction. Hence base catalyzed autoxidation 18 - labeled benzophenone was observed involved to any substantial extent. Less than 10% 0 12 16 in the oxidative cleavage of L in the mass spectrum of the product when lCOz18replaced KO 2 Attempts were made to detect via ESR, immediately following the mixing of K02 and olefin, the paramagnetic specia involved in this reaction. A well resolved spectrum of the corresponding anion radical could be recorded for -I (aN=2.84G, a =2.50G, a2(lj=l.O5G. l(2) a3=2.80G). The computer simulated spectrum overlapped the experimental one. Parsmagnetic specia were also detected for z
and Iw
but the poor resolution prevented identification.
The data indicates that for olefins I-VI the primary reaction is oxidative cleavage -5z of the double bond. As suggested previously , it is likely that the reaction proceeds by a preliminary electron transfer from 0 - to the electron poor double bond. The resulting 2 anion radical reactsin turn with surrounding molecular oxygen as sketched below.
Ar
Z 'c=c' R' 'Z
Ar\
.
AZ
+0-2
R=CH3,H Ar cpo <
HO'
Z
'C-Y? R'I 'Z o-t,
Ar
'c=o R'
or Et
L
Lee
(footnote 141
Z 'c-c' R'I I'Z
-
O-6 For compounds of Type 1 there is a second competing pathway which leads to substituted atropic acids. We suggest the following mechanism to rationalize their formation. The first
. Ar
Ar
CN 'C-C' CH," 'CN
/CN 'C=C CHf 'CN
'C=C' CH< 'CN
A -
J
O2
Ar
0 'C-E CH// 'CN 2
CN \C-&C:N H2C+ 1 $ Ar
-
it
o-o
C Ar -
0
-
step involves abstraction of the active allylic hydrogen. One would expect highest radical density in the allylic radical a to the ;r gives species g.
groups. Addition of oxygen to the radical A
Closure to a dioxetane and cleavage as shown to yield enone C finds pre-
.
cadent in the electrogenerated02- oxidation of benzyl
cyanide
to bensoic acid.l3
A
second electron transfer, addition of oxygen and oxidative cleavage of the cyan0 group leads to the desired product.
170. 52
4634
We have thus demonstrated poor olefins
yielding
noted above, similar
products products
that superoxide corresponding
are expected
to oxidative with electron
A report on these systems will be forthcoming
References
anion radical
readily reacts with electron
cleavage
of the double bond.
rich olefins
As
such as enol ethers.
shortly.
and Fcotnotes
1.
I. Fridovich, Act. Chem. Res., 5, 321 (1972); b) W. Bors, M. Saran, E. Lengfeldon, a) R. Sp%tt)and C. Michel, Curr.Top. Rad. Res. Quart., 2, 247 (1974); c) J.P. Henry, La Recherche, E, 370 (1975); d) I. Fridovich in Molecular Mechanisms of Oxygen Activation, 0. Hayaishi, ed., Academic Press, N.Y., (1974) p. 453.
2.
J.S. Valentine
3.
I. Rosenthal
4.
a)
5.
I. Rosenthal
6.
A. Primer
7.
and D.B. Curtis,
and A. Frimer,
J. Amer. Chem. Sot.,
Tet. Let.,
3731 (1975).
P. Muir Wood, FEBS Let., 2, 22 (1975); Israel J. Chem., 12, 891 (1974).
Olefin I
b)
Y.A. Ilan, D. Meisel
and A. Frimer,
Tet. Let.,
2805
and I. Rosenthal,
Tet. Let.,
2809 (1976).
was synthesized
9J, 224 (1975).
by the procedure
and G. Czapski,
(1976).
of E.D. Bergman
and E. Meyer,
Chem. Ber., 12 - A.I. Vogel, IV - B.B. Practical Organic Chemistry, John Wiley and Sons Inc., N.Y. c.1966) p. 717; Carson and R.W. Stoughton, J. Amer. Chem. Sot., so, 2825 (1928); 1 and E -5.T. Mowry, J. Amer. Chem. Sot., 67, 1050 (1945).
65, 446 (1932); 11 - F.G. Garbich Jr., J. Org. Chem., 21, 2322 U962);
8.
'H NMR (6, acetone-d ):VIIa-7_33(m,5H) 6.30 (d,lH,J=lHs) 5.94 (d,lH,J=lHz); VIIb-7.61 (d,ZH,J=5Hg) 7.25 (d,2H,J=SHz) 6.26 (d,lH,J=lHz) 5.90 (d,lH,J=lHz) 2.30 (s,~H);VII~-~.~O(~,ZH,J=~H~) 6.89 (d,W,J=5Hz) 6.22 (d,lH,J=lHz) 588 (d,lH,J=lHs) 3.83 (s,3H). -
9.
E.J. Skerret
and D. Woodcock,
J. Chem. Sot., 2806 (1952).
10.
a) G.A. Russel, Adv. Chem. Ser., 51, 112 (1965); 75, 174 (1968); b) G. Sosnovsky and E.H. Zaret in Organic Peroxides, Vol. I, D. Swern Ed., Wiley Interscience, N.Y. (1970) p. 517 ff.
11.
NO base catalyzed cf reference 5.
12.
I. Rosenthal,
13.
M. Tesuka, H. Hamada,
14.
Eithe f5 0 2 (functioning as an oxidizing agentlD) or starting material uence ) may serve as the electron recipients in this step.
15.
N. Kornblum,
16.
Dioxetanes are the probable intermediate in the oxidative cleavage and a-halo ketones, esters and carboxylic acids; see J.S. Fillipo, J.S. Valentine, J. Org. Chem., 41, 1078 (1976).
autooxidation
J. Labelled
was observed
Compounds
Y. Ohkatsu
in the reaction
& Radiopharmaceuticals,
and T. Osa, Denki Kagaku,
of KOH/crown
with
chalcones;
11, 317 (1976). s,
17 (1976). (in a chain seq-
Angew. Chem. Int. Ed. Eng., 14, 734 (1975). of a-keto, a-hydroxy, C. Chern and