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1,4-Dianion of acetophenone n-ethoxycarbonylhydrazone as a synthetic intermediate
Tetrahedron Letters,Vol.24,No.31,pp Printed in Great Britain
1,4-DIANION
OF ACETOPHENONE
N-ETHOXYCARBONYLHYDRAZONE
AS A SYNTHETIC
Noboru
Matsumura*,
Department
Akira
of Applied
pared
Various
derived
Kunugihara,
of aldehydes
from acetophenone
and Shigeo
University
Osaka
,&hydroxyketones
by the reaction
INTERMEDIATE
Chemistry, Sakai,
Abstract:
0040-4039/83 $3.00 + .OO 01983 Pergamon Press Ltd.
3239-3242,1983
of Osaka
and
&P-unsaturated with
compounds
dride,
carbonate,
ketones
1,4-dianion
N-ethoxycarbonylhydrazone
of -2 with carbonyl acyl chloride, and alkyl
Prefecture,
591, Japan
and ketones
the reaction
Yoneda*
(l-1with
such as ester, pyrazole
were
pre-
(2) which
is
butyllithium.
amide,
In
acid anhy-
derivatives
were
obtained
in good yields.
1,4-Dianion tion
as synthetic
preparative been
because
zone to carbonyl thesis
intermediates
significance.
limited
tophenone
organic
However,
compound
The reaction
We now wish 1,4-dianion
investigated4) to report
(2) which
of aldehydes
rated
ketones
were
bony1
compounds
and ketones
were
in good yields
A typical
procedure
and &&-unsaturated mmol)
was
added
-78 OC under added
dropwise
complete
fading
2h at -78 treated
cont.
HCl,
acidic
carbonyl
from 1 with
that
ace-
hydrolysis
un-
In the
when
the caralkyl
derivatives
of the reaction
intermediates.
of /3-hydroxyketones
THF solution
yellowish
of a carbonyl the reaction
(-78 "C) of -1 (2.42 (5.32 mmol) with stirring
brown
compound mixture
in vacua.
water,
3239
with
&&unsatu-
acyl chloride,
for the preparation
was removed
hand,
with 2, pyrazole
of butyllithium
acid,
and/or
On the other
reacted
compounds
butyllithium.
acid anhydride,
were
To a cooled
solution
acetic
on the syn-
the anion 1 to synthetic
with z,p-hydroxyketones
To the resulting
of the color,
facile
of various
derived
is descrived
a THF solution
and
of N-alkoxycarbonylhydrazono-ketones
by the cyclization
OC, and the solvent
with
behavior
amide,
carbonate
ketones:
a hexane
argon.
(1) underwent
study31
it was observed
led us to apply
in good yields.
such as ester, and alkyl
atten-
so far.
is readily
chloroformate obtained
In our preceding
the reaction
obtained
much
reactivities
application in organic synthesis has difficulty 2) in converting a hydra-
by hydrolysis.
finding
received
interesting
2-alkoxy-1,3,4-oxadiazoles,
This
reactions.
has not been well
to their
their
N-ethoxycarbonylhydrazone conditions.
reaction
owing
of the considerable
of 5-substituted
der mild
hydrazones 1) have
of N-monosubstituted
colored
solution
(2.18 mmol).
was
stirred
After
a
for additional
The residual
and methanol
at
was
mixture
(10 ml each),
and
was
3240
stirred for 2h at room temperature. After methanol was evaporated, the residue was extracted with ether, and the extract was washed with water, dried over anhydrous MgS04 and condensed under reduced pressure.
The residue was chromatographed on a silicagel column (CHC13) or preparative TLC (CHC13) to
give &hydroxyketone
(2) and/or &&unsaturated
ketone (4) (Scheme 1).
The
yields are shown in Table 1.
Scheme
1 C2H5OOC 2 n-BuLi -7 8 “C,THF
-
Hf
1.
Reaction
I!
R2
Carbonyl
a b
with
Coxpound
Yieldb) (%) R2
Ph
H
68
H
64
Ph
e
CH3CH2CH2
f
c) Yields
were
yields
when
the
(O)C'
carried
by column hydrolyses
out
90
CH3CH2CH2
24
42
46
14
at -78
'C in THF
carried
(86)C)
13
61
chromatography were
10
Ph
-(CH2)S-
reaction
-4
1
H
Qx
b) Isolated
2.a)
RI
d
a) The
and Ketones
CH3CH2CH2CH2CH2
c
PI+&
i
”
of Aldehydes
Entry
1
Li+ QN,..Li_
phAcH=C/,R1
+
3
Table
C2H5OOC
RI-C-R2
PhA&2
0”
!!
Ph+--..+,
t 1 I------+
-L’ ‘N i$ i:
CO)=)
(94)C)
for 2h.
and preparative out
23
TLC.
at SO 'V.
Next, the reaction of esters, amides, acid anhydrides, acyl chlorides with -2 were carried out under similar reaction conditions. In these cases, 5substituted 1-ethoxycarbonyl-3-phenyl pyrazoles 5 were obtained in good yields by the cyclization of the reaction intermediate A and the following dehydration of B.
The yields of 2 are shown in Table 2.
3241
Scheme
2
,COOC2H5 N-N
H+ A
Table 2.
Ph
v
R3 H
Reaction of Esters, Amides, Acid Anhydrides
Entry
and Acyl Chlorides with -2
Carbonyl Compound
Yield (%I -3) 1
R3
R4
Ph
CH30
CH3 H
n-C4HgO
36
n-C4HgO
11
CH3 H
(CH312N
37 38
Ph
(CH3)2N PhCOO
CH3 Ph
Cl
49
CH3
Cl
32
a) All products gave satisfactory
74
43 25
ir, mass, nmr and elemental analyses.
The reaction of diethyl carbonate with 2. gave pyrazole having PhCOCH2group at the 5 position in 22% yield. lined in Scheme 3.
The mechanistic interpretation is outIn a similar manner as seen in Scheme 2, the reaction
would be initiated by the C-C bond formation to give intermediate A'.
The intermediate A', in this case, would undergo nucleophilic attack by 2 to
afford intermediate B'. Subsequent ring closure would give C' and result in the formation of -6 by hydrolysis and dehydration. The reaction of methyl chloroformate with 2 also gave 5 in 42% yield.
3242
Scheme
3
C2+~500Cij;i:,+
C2,,50_~_OC2H5 -78”C.Zh
Ph’ki2
,COOC2H5
,, + A
-
Work
N-N PhvCH2COPh H
:
is in progress
to explore
the applicability
of 2 to other
organic
syntheses.
References 1) (a) C.F.Beam,
D.C.Reames,
and R.M.Sandifer, L.W.Dasher
1978,
Synthesis,
1979,
469;
4) F.E.Ziegler (Received
Y.Otsuji
in Japan
ibid.,
and W.T.Stolle,
and T.Nakai,
Chem.
J. Org. Chem., 43,
Chem.
(n) T.Nakai
465;
Commun.,
1404
(k) A.R.Chamberlin
and K.Mikami,
1979,
J. Org. Chem.,
J.C.S.
J. Org. Chem., 1243;
ibid.,
1980,
and
1099;
Lett.,
3,
(1978); and 1979,
and K.Mikami, (p) T.Mimura
931.
and E.Imoto,
29 March
(e) E.Vedejs
and R.H.Shapiro,
1978,
C.E.Harris,
(c) J.E.Stemke G.T.Rivers
and F.T.Bond,
(1) T.Nakai
J. Am. Chem.
and P.A.Wender,
(1975);
and A.G.M.Barrett,
Lett.,
and M.Silvestri,
and P.L.Fuchs,
3) N.Matsumura,
44;
779
N.L.Shealy
(d) W.G.Dauben,
2951;
J.E.Stemke
Chem.
(0) T.Mimura 1980,
1815;
and R.H.Shapiro,
and K.Mikami,
ibid.,
Murry
1979,
1976,
12,
(f) M.f.Lipton
(g) R.M.Adlington
and K.Mikami,
(m) T.Nakai
(a) J.E.Mc Sacks
Lett., 135;
(i) K.J.Kolonko
and T.Nakai, 2)
1977,
(h) A.R.Chamberlin,
1071;
(j) T.Nakai
ibid.,
Tetrahedron
Lett.,
(1978);
1081;
Lett.,
W.M.Hollinger, (b) D.C.Reames,
(1975);
1975,
(1978);
F.T.Bond,
514
Tetrahedron
Tetrahedron
147
40,
J. Het. Chem.,
W.T.Zimmerman,
1409
Chem.,
L.W.Dasher,
and R.M.Sandifer,
and,F.T.Bond,
43,
J.Org.
C.E.Harris,
J. Org. Chem.,
3,
Sot., 97,
7372
(1975).
Kagaku
Kaishi,
Nippon
J. Org. Chem., 1983)
42,
2001
1502
(1975);
1976,
(1977).
(b) C.E.
782.
1,4-DIANION
OF ACETOPHENONE
N-ETHOXYCARBONYLHYDRAZONE
AS A SYNTHETIC
Noboru
Matsumura*,
Department
Akira
of Applied
pared
Various
derived
Kunugihara,
of aldehydes
from acetophenone
and Shigeo
University
Osaka
,&hydroxyketones
by the reaction
INTERMEDIATE
Chemistry, Sakai,
Abstract:
0040-4039/83 $3.00 + .OO 01983 Pergamon Press Ltd.
3239-3242,1983
of Osaka
and
&P-unsaturated with
compounds
dride,
carbonate,
ketones
1,4-dianion
N-ethoxycarbonylhydrazone
of -2 with carbonyl acyl chloride, and alkyl
Prefecture,
591, Japan
and ketones
the reaction
Yoneda*
(l-1with
such as ester, pyrazole
were
pre-
(2) which
is
butyllithium.
amide,
In
acid anhy-
derivatives
were
obtained
in good yields.
1,4-Dianion tion
as synthetic
preparative been
because
zone to carbonyl thesis
intermediates
significance.
limited
tophenone
organic
However,
compound
The reaction
We now wish 1,4-dianion
investigated4) to report
(2) which
of aldehydes
rated
ketones
were
bony1
compounds
and ketones
were
in good yields
A typical
procedure
and &&-unsaturated mmol)
was
added
-78 OC under added
dropwise
complete
fading
2h at -78 treated
cont.
HCl,
acidic
carbonyl
from 1 with
that
ace-
hydrolysis
un-
In the
when
the caralkyl
derivatives
of the reaction
intermediates.
of /3-hydroxyketones
THF solution
yellowish
of a carbonyl the reaction
(-78 "C) of -1 (2.42 (5.32 mmol) with stirring
brown
compound mixture
in vacua.
water,
3239
with
&&unsatu-
acyl chloride,
for the preparation
was removed
hand,
with 2, pyrazole
of butyllithium
acid,
and/or
On the other
reacted
compounds
butyllithium.
acid anhydride,
were
To a cooled
solution
acetic
on the syn-
the anion 1 to synthetic
with z,p-hydroxyketones
To the resulting
of the color,
facile
of various
derived
is descrived
a THF solution
and
of N-alkoxycarbonylhydrazono-ketones
by the cyclization
OC, and the solvent
with
behavior
amide,
carbonate
ketones:
a hexane
argon.
(1) underwent
study31
it was observed
led us to apply
in good yields.
such as ester, and alkyl
atten-
so far.
is readily
chloroformate obtained
In our preceding
the reaction
obtained
much
reactivities
application in organic synthesis has difficulty 2) in converting a hydra-
by hydrolysis.
finding
received
interesting
2-alkoxy-1,3,4-oxadiazoles,
This
reactions.
has not been well
to their
their
N-ethoxycarbonylhydrazone conditions.
reaction
owing
of the considerable
of 5-substituted
der mild
hydrazones 1) have
of N-monosubstituted
colored
solution
(2.18 mmol).
was
stirred
After
a
for additional
The residual
and methanol
at
was
mixture
(10 ml each),
and
was
3240
stirred for 2h at room temperature. After methanol was evaporated, the residue was extracted with ether, and the extract was washed with water, dried over anhydrous MgS04 and condensed under reduced pressure.
The residue was chromatographed on a silicagel column (CHC13) or preparative TLC (CHC13) to
give &hydroxyketone
(2) and/or &&unsaturated
ketone (4) (Scheme 1).
The
yields are shown in Table 1.
Scheme
1 C2H5OOC 2 n-BuLi -7 8 “C,THF
-
Hf
1.
Reaction
I!
R2
Carbonyl
a b
with
Coxpound
Yieldb) (%) R2
Ph
H
68
H
64
Ph
e
CH3CH2CH2
f
c) Yields
were
yields
when
the
(O)C'
carried
by column hydrolyses
out
90
CH3CH2CH2
24
42
46
14
at -78
'C in THF
carried
(86)C)
13
61
chromatography were
10
Ph
-(CH2)S-
reaction
-4
1
H
Qx
b) Isolated
2.a)
RI
d
a) The
and Ketones
CH3CH2CH2CH2CH2
c
PI+&
i
”
of Aldehydes
Entry
1
Li+ QN,..Li_
phAcH=C/,R1
+
3
Table
C2H5OOC
RI-C-R2
PhA&2
0”
!!
Ph+--..+,
t 1 I------+
-L’ ‘N i$ i:
CO)=)
(94)C)
for 2h.
and preparative out
23
TLC.
at SO 'V.
Next, the reaction of esters, amides, acid anhydrides, acyl chlorides with -2 were carried out under similar reaction conditions. In these cases, 5substituted 1-ethoxycarbonyl-3-phenyl pyrazoles 5 were obtained in good yields by the cyclization of the reaction intermediate A and the following dehydration of B.
The yields of 2 are shown in Table 2.
3241
Scheme
2
,COOC2H5 N-N
H+ A
Table 2.
Ph
v
R3 H
Reaction of Esters, Amides, Acid Anhydrides
Entry
and Acyl Chlorides with -2
Carbonyl Compound
Yield (%I -3) 1
R3
R4
Ph
CH30
CH3 H
n-C4HgO
36
n-C4HgO
11
CH3 H
(CH312N
37 38
Ph
(CH3)2N PhCOO
CH3 Ph
Cl
49
CH3
Cl
32
a) All products gave satisfactory
74
43 25
ir, mass, nmr and elemental analyses.
The reaction of diethyl carbonate with 2. gave pyrazole having PhCOCH2group at the 5 position in 22% yield. lined in Scheme 3.
The mechanistic interpretation is outIn a similar manner as seen in Scheme 2, the reaction
would be initiated by the C-C bond formation to give intermediate A'.
The intermediate A', in this case, would undergo nucleophilic attack by 2 to
afford intermediate B'. Subsequent ring closure would give C' and result in the formation of -6 by hydrolysis and dehydration. The reaction of methyl chloroformate with 2 also gave 5 in 42% yield.
3242
Scheme
3
C2+~500Cij;i:,+
C2,,50_~_OC2H5 -78”C.Zh
Ph’ki2
,COOC2H5
,, + A
-
Work
N-N PhvCH2COPh H
:
is in progress
to explore
the applicability
of 2 to other
organic
syntheses.
References 1) (a) C.F.Beam,
D.C.Reames,
and R.M.Sandifer, L.W.Dasher
1978,
Synthesis,
1979,
469;
4) F.E.Ziegler (Received
Y.Otsuji
in Japan
ibid.,
and W.T.Stolle,
and T.Nakai,
Chem.
J. Org. Chem., 43,
Chem.
(n) T.Nakai
465;
Commun.,
1404
(k) A.R.Chamberlin
and K.Mikami,
1979,
J. Org. Chem.,
J.C.S.
J. Org. Chem., 1243;
ibid.,
1980,
and
1099;
Lett.,
3,
(1978); and 1979,
and K.Mikami, (p) T.Mimura
931.
and E.Imoto,
29 March
(e) E.Vedejs
and R.H.Shapiro,
1978,
C.E.Harris,
(c) J.E.Stemke G.T.Rivers
and F.T.Bond,
(1) T.Nakai
J. Am. Chem.
and P.A.Wender,
(1975);
and A.G.M.Barrett,
Lett.,
and M.Silvestri,
and P.L.Fuchs,
3) N.Matsumura,
44;
779
N.L.Shealy
(d) W.G.Dauben,
2951;
J.E.Stemke
Chem.
(0) T.Mimura 1980,
1815;
and R.H.Shapiro,
and K.Mikami,
ibid.,
Murry
1979,
1976,
12,
(f) M.f.Lipton
(g) R.M.Adlington
and K.Mikami,
(m) T.Nakai
(a) J.E.Mc Sacks
Lett., 135;
(i) K.J.Kolonko
and T.Nakai, 2)
1977,
(h) A.R.Chamberlin,
1071;
(j) T.Nakai
ibid.,
Tetrahedron
Lett.,
(1978);
1081;
Lett.,
W.M.Hollinger, (b) D.C.Reames,
(1975);
1975,
(1978);
F.T.Bond,
514
Tetrahedron
Tetrahedron
147
40,
J. Het. Chem.,
W.T.Zimmerman,
1409
Chem.,
L.W.Dasher,
and R.M.Sandifer,
and,F.T.Bond,
43,
J.Org.
C.E.Harris,
J. Org. Chem.,
3,
Sot., 97,
7372
(1975).
Kagaku
Kaishi,
Nippon
J. Org. Chem., 1983)
42,
2001
1502
(1975);
1976,
(1977).
(b) C.E.
782.