- Email: [email protected]
Insecticidal amides. Synthesis of natural 2(E ),4(E ),10(E )-pipercide, its 2(E ), 4(E ), 10 (Z )- stereomer, and related isobutylamides
Tetrahedron Letters,Vol.25,No.38,pp Prknted in Great Britain
INSECTICIDAL
AMIDES.
PIPERCIDE,
4267-4270,1984
SYNTHESIS
ITS 2(E),
Leslie
Natural
are synthesised, knock
down.
2@),4(E),lO(E)-
4(E), lo(z)- STEREOMER, ISOBUTYLAMIDES
Crombie
and Raymond
of Chemistry, Nottingham,
Summary:
OF NATUPAL
RELATED
Department
0040-4039/84 $3.00 + .oo 01984 Pergamon Press Ltd.
AND
Denman
The University,
NG7
2RD.
[all (lJ)]pipercide and its 2(E),4(E),lO(Z)the latter
having
lO,ll-Dihydro-
superior
insecticidal
stereomer
potency
and lO,ll-dehydropipercides
and
are also
prepared. Various
natural
in the Compositae, activity, chain double bonds
having
substantial
been
and Rutaceae within
(z)/(z)-
counting
recently
carbon
work we have
nigrum
bean-weevil
synthesised
in the light of findings insecticidal
2(~),4(~),lO(E)-Pipercide was
continuous
hexane
extraction
derivative
(2).4
Grignard
with methyl
converted
trimethylamine
into
or perhaps
more
more
bond of
to
isobutylamide pipercide
(6),
to be insecticidally chinensis).3
pipercide
double
first double
substituent,
was
synthesised
aliphatic
has
active
In the present
10(z)-
and its
stereomer
series,
to
their
formation
a virtually
The latter
with
to the
in dry chloroform.6 4267
piperonal
was then heated
gave
the
at 75°C for
in hexamethylphosphoramide.5
stereospecific
the pyranyloxy-group
1. 1,6-
employing
as the tetrahydropyranyl
and reaction
iodide
to Scheme
via a procedure
and then protected
(4) was now oxidised N-oxide -
according
its monobromide
triphenoxyphosphonium
and transformed
The iodo-product
insecticidal
(1) the acid has a
or perhaps
the
especially
is (Z)-, and there is if this is stereomutated
end,
activity
in the purely
(3) in 70% yield.
In one step this effected olefin
In
found
potencies.
Hexanediol
diol
Usually
and reported
relative
half-protected
and y=2,3
undecatrienoic
both natural
possess
(l)? z=1,2,
(Callosobruchus
compare,
lh
atoms,
from the carboxyl
in insecticidal
from Piper
the Adzuki
families
geometry.'
a 2(E),4(~)-
isobutylamides
a structure
an ll-(3,4-methylenedioxyphenyl)-
isolated
against
or
diminution
More
unsaturated
(E)- stereochemistry,
(g)/(z)-
the y grouping,
carrying
embraced
of 10 to 20 or more
bonds with
(g)-.2
Piperaceae
generally
length
straight-chain
dehydration
to the iodide, (E)-aldehyde Wadsworth-Emmons
to the
(E)-
in high yield. (5) using
anhydrous
reaction,7
4269
and assignments for either were
assigned
Evaluation
effective
(14).
Chemical
by specific
than
proton
shifts
has shown
the all-(s)
be published
of isomeric
for C-3 and C-5, being
inhomogeneity very
close,
decoupling.
of isobutylamides
(Musca domestica)
will
There was no evidence
are as shown.
(6) or
(6) and
(14) against
the common
both as regards
kill
housefly
is indeed
that the 2(E),4(g),lO(Z)-stereomer and knockdown.16
more
Full details
elsewhere.
References 1.
L. Crombie
2.
e.g. L. Crombie
and A.H.A.
Krasinski,
3.
M. Miyakado, I. Nakayama, 1979, 43, 1609.
4.
O.L. Chapman, K.C. Mattes, 1978, 100, 4878.
5.
1972, 37, (a) R.O. Hutchins, M.G. Hutchins and C.A. Milewski, J.Org.Chem., (b) S.R. Landauer and H.N. Rydon, J.Chem.Soc., 1953, 2224. 4190;
6.
Collective Volume 5'. Ed. (a) V. Franzen, 'Organic Synthesis: (b) W.J. Hickinbottom, H.E. Baumgarten, Wiley, New York, 1973, p.872; 'Reactions of Organic Compounds', 3rd Ed., Longmans, London, 1957, p.420. -
7.
R.S. Burden
and J.D. Shah,
Chem.
H. Yoshioka
and L. Crombie,
R.S.
and Ind.,
J.Chem.Soc.,
1955,
1962,
and N. Nakatani,
Sheridan
J.Chem.Soc.,
and J.A. Klun,
1969,
983.
4244.
2477.
Agric.Biol.Chem., J.Am.Chem.Soc.,
4270
8.
212(log ~4.41), 261(4.63), all-(E)-Pipercide had M+ 355.2146, Amax(EtOH): The 268i(4.59) and 304(3.78)nm, vmax(KBr): 3300, 1660, 1638, 1620cm-'. 'Hmr spectrum (250 MHz, CDCl,) showed resonances at 6: 0.92 (d,6H, J6.7Hz; 3",4"-Me), 1.47(m,4H; 7,8-gz's), 1.81(m,lH; 2"-E), 2.17(m,4H; 6,9-(X2's), 3.16 (dt, 2H; l"-g), 5.59 (broad t, 1H; NE), 5.76 (d,lH,z15.3Hz; 2-H) 5.60 (t, 1H; 10-H), 6.06 (t, lH, 5-H), 6.15 (dd, lH, 5.93 (s,2H; .OC$O, 11-c), 6.76 (s, 2H; 2' and J15 and 9.5Hz; 4-i), 6.29 (d, lH, J15.5Hz; 5'-H), 6.90 (s, lH, 6'-H), 7.20 (dd, lH, J 14.8, 10.1 Hz, 3-H): from the sample melted at 120°C after prior softening (lit.3 m.p. cyclohexane, 114 -115OC).
9.
An earlier synthesis of pipercide has been 1979, 2413. H. Yoshioka, sric.Biol.Chem.,
10.
Dr. Miyakado
has kindly
supplied
us with
reported:
M. Miyakado
the infra-red
and 60MHz
and
(CDCl,)
1
Our 2(E),4(E),lO(Z), isomer (14) is Hmr spectra of natural pipercide. isomer (6) bears clearly different, and our synthetic 2(E),4(E),lO(E) A small sample of Dr. Miyakodo's synthetic much closer resemblance. pipercide in our hands partially melted at 75"C, the last material On examination at 25OMHz (CDC13) two closely disappearing at 113°C. spaced methylenedioxy signals were observed, 6 5.93 and 5.95. A doublet of to a doublet at 6.31, J11.6Hz triplets at 5.53, J 11.6Hz,coupled 10(z)- material whilst a doublet at 6.29, J,15.6Hz signified signified Characteristic of the 2(E),4(E),lO(Z)the 11-g of the 10(E)-olefin. isomer (see below), the multiplet at 2.31 due to the 9-CHz, was also present. Integration indicates 55% 2(E),4(E),lO(Z)and 45% 2(E), 4(E), 10(E)- pipercides. 11.
M. Miyakado,
12.
W. Feuerstein
13.
L. Friedman
14.
E. Winterfeldt,
15.
had M+ 355.2108, Amax(EtOH): 209(Log ~4.27)~ 2(E), 4(E), 10(Z)-Pipercide 261(4.45), 297 Tnfl. (3.46), v 3320, 1660, 1630, 1620 cm-l (KBr): The lHmr spectrum (250 MHz, CD%!;) showed resonances at 6:0.91 (d, 6H , J6.7Hz; 3",4"-Me), 1.51 (m, 4H; 7,8-Ci2's), 1.80 (septet, 1H; 2";) 2.13 (m, 2H; 6-CH2), 2.30 (m, 2H; 9-C!2), 3.14 (t, 2H, 1"-H), 5.52 (dt, lH, 511.6Hz; 10-H), 5.85 (d, lH, J15Hz; 2-H), 5.93 (s, 2H ; -OCH20-), 6.02 (t, 1H; 5-H), 6.06 (dd, lH, 514.5, 9.3Hz; 4-s), 6.30 (d, lH, J 11.6; 7.34 (dd, lH, 215.0, lO.OHz; 11-H), 6.78 (m, 3H; 2',5',6'+), 7-E). From cyclohexane, it had m.p. 88°C after prior softening.
16.
We thank
I. Nakayama
g.,
and H. Schechter, Synthesis,
Dr. M.H.
for arranging (Received
and H. Yoshioka,
and M.Heimann,
Black,
Wellcome
the insecticidal
in UK 10 July
J.Org.Chem.,
1975,
1984)
Agric.Biol.Chem.,1980,
1901, 2,
44,
1701.
1468. 1960, 25,
877.
617.
Research
tests.
Laboratories,
Berkhamsted,
INSECTICIDAL
AMIDES.
PIPERCIDE,
4267-4270,1984
SYNTHESIS
ITS 2(E),
Leslie
Natural
are synthesised, knock
down.
2@),4(E),lO(E)-
4(E), lo(z)- STEREOMER, ISOBUTYLAMIDES
Crombie
and Raymond
of Chemistry, Nottingham,
Summary:
OF NATUPAL
RELATED
Department
0040-4039/84 $3.00 + .oo 01984 Pergamon Press Ltd.
AND
Denman
The University,
NG7
2RD.
[all (lJ)]pipercide and its 2(E),4(E),lO(Z)the latter
having
lO,ll-Dihydro-
superior
insecticidal
stereomer
potency
and lO,ll-dehydropipercides
and
are also
prepared. Various
natural
in the Compositae, activity, chain double bonds
having
substantial
been
and Rutaceae within
(z)/(z)-
counting
recently
carbon
work we have
nigrum
bean-weevil
synthesised
in the light of findings insecticidal
2(~),4(~),lO(E)-Pipercide was
continuous
hexane
extraction
derivative
(2).4
Grignard
with methyl
converted
trimethylamine
into
or perhaps
more
more
bond of
to
isobutylamide pipercide
(6),
to be insecticidally chinensis).3
pipercide
double
first double
substituent,
was
synthesised
aliphatic
has
active
In the present
10(z)-
and its
stereomer
series,
to
their
formation
a virtually
The latter
with
to the
in dry chloroform.6 4267
piperonal
was then heated
gave
the
at 75°C for
in hexamethylphosphoramide.5
stereospecific
the pyranyloxy-group
1. 1,6-
employing
as the tetrahydropyranyl
and reaction
iodide
to Scheme
via a procedure
and then protected
(4) was now oxidised N-oxide -
according
its monobromide
triphenoxyphosphonium
and transformed
The iodo-product
insecticidal
(1) the acid has a
or perhaps
the
especially
is (Z)-, and there is if this is stereomutated
end,
activity
in the purely
(3) in 70% yield.
In one step this effected olefin
In
found
potencies.
Hexanediol
diol
Usually
and reported
relative
half-protected
and y=2,3
undecatrienoic
both natural
possess
(l)? z=1,2,
(Callosobruchus
compare,
lh
atoms,
from the carboxyl
in insecticidal
from Piper
the Adzuki
families
geometry.'
a 2(E),4(~)-
isobutylamides
a structure
an ll-(3,4-methylenedioxyphenyl)-
isolated
against
or
diminution
More
unsaturated
(E)- stereochemistry,
(g)/(z)-
the y grouping,
carrying
embraced
of 10 to 20 or more
bonds with
(g)-.2
Piperaceae
generally
length
straight-chain
dehydration
to the iodide, (E)-aldehyde Wadsworth-Emmons
to the
(E)-
in high yield. (5) using
anhydrous
reaction,7
4269
and assignments for either were
assigned
Evaluation
effective
(14).
Chemical
by specific
than
proton
shifts
has shown
the all-(s)
be published
of isomeric
for C-3 and C-5, being
inhomogeneity very
close,
decoupling.
of isobutylamides
(Musca domestica)
will
There was no evidence
are as shown.
(6) or
(6) and
(14) against
the common
both as regards
kill
housefly
is indeed
that the 2(E),4(g),lO(Z)-stereomer and knockdown.16
more
Full details
elsewhere.
References 1.
L. Crombie
2.
e.g. L. Crombie
and A.H.A.
Krasinski,
3.
M. Miyakado, I. Nakayama, 1979, 43, 1609.
4.
O.L. Chapman, K.C. Mattes, 1978, 100, 4878.
5.
1972, 37, (a) R.O. Hutchins, M.G. Hutchins and C.A. Milewski, J.Org.Chem., (b) S.R. Landauer and H.N. Rydon, J.Chem.Soc., 1953, 2224. 4190;
6.
Collective Volume 5'. Ed. (a) V. Franzen, 'Organic Synthesis: (b) W.J. Hickinbottom, H.E. Baumgarten, Wiley, New York, 1973, p.872; 'Reactions of Organic Compounds', 3rd Ed., Longmans, London, 1957, p.420. -
7.
R.S. Burden
and J.D. Shah,
Chem.
H. Yoshioka
and L. Crombie,
R.S.
and Ind.,
J.Chem.Soc.,
1955,
1962,
and N. Nakatani,
Sheridan
J.Chem.Soc.,
and J.A. Klun,
1969,
983.
4244.
2477.
Agric.Biol.Chem., J.Am.Chem.Soc.,
4270
8.
212(log ~4.41), 261(4.63), all-(E)-Pipercide had M+ 355.2146, Amax(EtOH): The 268i(4.59) and 304(3.78)nm, vmax(KBr): 3300, 1660, 1638, 1620cm-'. 'Hmr spectrum (250 MHz, CDCl,) showed resonances at 6: 0.92 (d,6H, J6.7Hz; 3",4"-Me), 1.47(m,4H; 7,8-gz's), 1.81(m,lH; 2"-E), 2.17(m,4H; 6,9-(X2's), 3.16 (dt, 2H; l"-g), 5.59 (broad t, 1H; NE), 5.76 (d,lH,z15.3Hz; 2-H) 5.60 (t, 1H; 10-H), 6.06 (t, lH, 5-H), 6.15 (dd, lH, 5.93 (s,2H; .OC$O, 11-c), 6.76 (s, 2H; 2' and J15 and 9.5Hz; 4-i), 6.29 (d, lH, J15.5Hz; 5'-H), 6.90 (s, lH, 6'-H), 7.20 (dd, lH, J 14.8, 10.1 Hz, 3-H): from the sample melted at 120°C after prior softening (lit.3 m.p. cyclohexane, 114 -115OC).
9.
An earlier synthesis of pipercide has been 1979, 2413. H. Yoshioka, sric.Biol.Chem.,
10.
Dr. Miyakado
has kindly
supplied
us with
reported:
M. Miyakado
the infra-red
and 60MHz
and
(CDCl,)
1
Our 2(E),4(E),lO(Z), isomer (14) is Hmr spectra of natural pipercide. isomer (6) bears clearly different, and our synthetic 2(E),4(E),lO(E) A small sample of Dr. Miyakodo's synthetic much closer resemblance. pipercide in our hands partially melted at 75"C, the last material On examination at 25OMHz (CDC13) two closely disappearing at 113°C. spaced methylenedioxy signals were observed, 6 5.93 and 5.95. A doublet of to a doublet at 6.31, J11.6Hz triplets at 5.53, J 11.6Hz,coupled 10(z)- material whilst a doublet at 6.29, J,15.6Hz signified signified Characteristic of the 2(E),4(E),lO(Z)the 11-g of the 10(E)-olefin. isomer (see below), the multiplet at 2.31 due to the 9-CHz, was also present. Integration indicates 55% 2(E),4(E),lO(Z)and 45% 2(E), 4(E), 10(E)- pipercides. 11.
M. Miyakado,
12.
W. Feuerstein
13.
L. Friedman
14.
E. Winterfeldt,
15.
had M+ 355.2108, Amax(EtOH): 209(Log ~4.27)~ 2(E), 4(E), 10(Z)-Pipercide 261(4.45), 297 Tnfl. (3.46), v 3320, 1660, 1630, 1620 cm-l (KBr): The lHmr spectrum (250 MHz, CD%!;) showed resonances at 6:0.91 (d, 6H , J6.7Hz; 3",4"-Me), 1.51 (m, 4H; 7,8-Ci2's), 1.80 (septet, 1H; 2";) 2.13 (m, 2H; 6-CH2), 2.30 (m, 2H; 9-C!2), 3.14 (t, 2H, 1"-H), 5.52 (dt, lH, 511.6Hz; 10-H), 5.85 (d, lH, J15Hz; 2-H), 5.93 (s, 2H ; -OCH20-), 6.02 (t, 1H; 5-H), 6.06 (dd, lH, 514.5, 9.3Hz; 4-s), 6.30 (d, lH, J 11.6; 7.34 (dd, lH, 215.0, lO.OHz; 11-H), 6.78 (m, 3H; 2',5',6'+), 7-E). From cyclohexane, it had m.p. 88°C after prior softening.
16.
We thank
I. Nakayama
g.,
and H. Schechter, Synthesis,
Dr. M.H.
for arranging (Received
and H. Yoshioka,
and M.Heimann,
Black,
Wellcome
the insecticidal
in UK 10 July
J.Org.Chem.,
1975,
1984)
Agric.Biol.Chem.,1980,
1901, 2,
44,
1701.
1468. 1960, 25,
877.
617.
Research
tests.
Laboratories,
Berkhamsted,