Note: Descriptions are shown in the official language in which they were submitted.
i~3~32
This invention relates to novel insecticidal compounds
of the formula:
R 0 0
~R ~ OCH3
wherein each R is independently chloro, fluoro, methyl, or
methoxy and is a divisional of Canadian application Serial
No. 332~130, filed July 19, 1979. It also relates to
methods employing the above compounds as insecticides.
Serial No. 332,130 is directed to compounds of the
formula:
s~Rm
~0 ~CNHCI~IH~ R2(CH ) n--R3
\R ~1 ~ .
wherein each R is independently chloro, fluoro,
methyl, or methoxy, with the pro~iso that when n is
: O, one R is chloro, and R3 is 3-(trifluoromethyl)-
phenyl or 2-chloro~5-(trifluoromethyl)phenyl, the
other R can zdditionally represent hydrogen; X is
oxygen or sulfur; Rl is chloro, methyl, or ethyl; R2
o O
is 0, S, S, or S; each of m and n is independently
O
0 or 1; R3 is
''~.
~ ~3~L;232
~ ..
--2--
~lj when n = 1, phenyl or substituted
phenyl, and
(2) when n = 0, substituted phenyl, in
either instance, substituted phenyl
S being ~a) 3,5-dimethylphenyl or (b) a
radical of the formula
zl
~2
wherein each Z independently represents
: (1) Br,
. (2) Cl, or
(3) F;
zl represents
(1) CF3, ~:
: (2) OCF3,
(33 O~2Fs~ or
2 (4) CF2cF2H; and
Z represents
(1) methyl,
(2) ethyl, or
(3) methoxy;
with the further limitation that the
entire substituted phenyl radical
- bears
(1) at least one Z or zl,
1~3:123;2
(2) not more than 4 substi-
tuents, when all substi-
tuents are halo substi-
tuents;
(3) not more than 3 substi-
tuents, when any one sub-
stituent is other than halo;
and
(4) not more than 2 different
substituents;
and wherein positions on the pyridine ring are as
follows:
(1) the nitrogen to pyridine bond is at
the 2-position of the pyridine ring,
the -R2-(CH2)n-R3 group is at the
5-position of the pyridine ring, and
any Rl is at the 4- or 6-position of
the pyridine ring; or
(2) the nitrogen to pyridine bond is at
the 3~position of the pyridine ring,
the -R2-(CH2)n-R3 group is at the
6-pos tion of the pyridine ring, and
any R is at the 5~position o the
pyridine ring;
and the acid addition salts and N-oxides thereof.
~L~3~3Z
--4~
Detailed Description of the Invention
For the purposes of the present appli-
cation, the compounds of this invention are named as
substituted ureas, with numbering as follows:
/30j---CNHCNH~R~a~CH~)n_R
Thus, the compounds are named as 1-(2-substituted or
- 2,6-disubstituted benzoyl)-3-(subs~ituted pyridinyl)-
ureas, N-oxides thereof, or acid addition salts
thereof.
The compounds of the pxesent invention are
rea;dily prepared by the reaction of a benzoyl iso-
cyanate or benzoyl isothiocyanate of the formula
~3~23Z
,~ ..
,R
o\ O / ~-C-NCX
~ ~-
with an aminopyridine of the formula
,
/ m
H2N ~ R -(CH2) n~R3
\N
or an N-oxide thereof. The reaction is a known type
of reaction, cf. U.S. 3,748,356. The reaction is
conveniently conducted in an organic solvent such as
ethyl acetate, at room temperature, and with equi~
molar amounts of the reactants. :~
The acld addition salts~are prepared by
reacting a benzoyl urea or benzoyl thiourea product
with the desired acid, in conventional procedures.
Acids having a pKa of 3.0 or lower are preferred, and -
generally the mineral acids are preferred. ~
The benozyl isocyanates which serve as ;
starting materials are prepared by the reaction of
the corresponding benzamide with oxalyl chloride by
the method of Speziale et al., J. ~. Chem. 27, 3742
(1962). The benzoyl isothiocyanates are prepared in
known procedures by reacting the corresponding
benzoyl chlorides with an inorganic thiocyanate, such
as ammonium thiocyanate, lead thiocyanate, etc.
~L~L3~Z3'~
, ~ .
The aminopyridines to be employed as
starting materials are prepared from the corre-
sponding halonitropyridines:
,
/4X
02N ~ 3 ~ ~ halo
o;~
The halonitropyridine is condensed with a phenol,
thiophenol, benzyl alcohol, or benzyl mercaptan of
the formula E~R2-(CH2)n-R3 and the resulting nitro
compound
/4XRm
02N ~ R' (CH )n~R3
is reduced. The former reaction is conducted in a
solvent such as DM~, DMSO, etc. and in the presence
of a base, such as triethylamine, KOH, LiOH, etc, to
serve as a hydrogen halide acceptor. Preferred
conditions are equimolar amounts of the reactants in
DMF, at room temperature, and with lithium hydroxide
as base. The reduction can be carried out in any of
various prior art procedures, including SnC12/HCl,
catalytic hydrogenation, and powdered iron with
ammonium chloride. Preferred conditions are powdered
iron and ammonium chloride.
Many of the halonitropyridlnes are com-
merically available and all are prepared by known
procedures. The 6-halo-3-nitropyridines, bearing an
~L~3~;~3Z
. ~ .
Rl substituent if desired, are readily prepared by
the methods of Acharya et al., Chem. Abst. 58, 5623c
(1963), Batkowski, Chem. Abst. 70, 106327x (1969),
and Hawkins et al., J. ~. Chem. 14, 328 (1949).
The 5-halo-2-nitropyridines are also readily pre-
pared, by bromination of a 2-aminopyridine to a
2-amino-5-bromopyridine, in accordance with the
procedure of Org. Syn. Coll. 5, 346 (John Wiley and
Sonsi N.Y., 1973); the 2-aminopyridine can also bear
an R substituent at the 4- or 6-position, in accordance
with the definition of the final products of the
present invention. Although condensation with a
HR2-(CH2)n-R3 compound bearing electron donating
substituents can be carried out directly with a
2-amino-5-bromopyridine (see Example 18, below), the
2-amino~5-bromopyridine compound can also be oxidized
to the corresponding 5-bromo-2-nitropyridine compound,
which undergoes the condensation regardless of the
identity of substituents.
The aminopyridine oxides are prepared in
prior art procedures, see Deady, Synthetic Communica-
tions 7(8), 509-514 11977) and Oxidation, ed. by Augustine,
especially Chapter 5 (Marcel Dekker, Inc., N.Y. 1969).
These and numerous other syntheses of
pyridine compounds are well known in the literature
and are well reviewed in P~ridine and Its Derivatives,
ed. by Klingsberg, especially Parts 2 and 3 (Inter-
scie~nce Publishers Inc., N.Y., 1961 and 1962).
Many of the phenols, thiophenols, benzyl
alcohols, and benzyl mercaptans which serve as
starting materials are also commercially available.
~3~L23Z
All can be prepared in prior art procedures. A
convenient procedure for the conversion of a phenol
to a thiophenol, or a benzyl alcohol to a benzyl
mercaptan, is that of Newman et al., J. Org. Chem.
31, 3980 (1966).
The following examples illustrate the
synthesis of the compounds of the present invention.
EXAMPLE 1: 6-(4-CHLOROPHENYLTHIO)-3-NITROPYRIDINE
6-Chloro-3-nitropyridine (4.0 grams) and
4-chlorothiophenol (3.7 grams) were mixed in 100 ml.
of dry DMF and lithium hydroxide (1.2 grams~ added
portionwise. After the reaction mixture had stirred
for about S minutes, it dar~ened and became warm. It
was allowed to stir with a drying tube for 4 hours,
poured over ice water and the product separated by
filtration. It was crystallized from ethyl acetate-
ethanol, yield 5.0 grams, m.p. 13~ 136C.
Calc. for CllH7ClN2O2S: C, 49.54; H, 2-56; N~ 10-50-
Found: C, 49.82; H, 2.36; N, 10.60.
EXAMPLE 2: 6-(3,5-DIMETHYLPHENOXY)-3-NITROPYRIDINE
6-Chloro-3-nitropyridine (9.5 grams; 0.06
mole), 3,5-dimethylphenol (7.2 grams; 0.06 mole), and
lithium hydroxide (4.0 grams) were mixed in 100 ml.
of dimethyl sulfoxide, and the reaction mixture was
stirred overnight (about 17 hours~ at room tempera-
ture. The reaction mixture was then poured into ice
water. The product was separated by filtration and
crystallized from ethyl acetate hexanes, yield 9.5
grams, m.p. 94-95C.
Calc for C13H12N2O3: C, 63.93; H, 4.93; N, 11.47
Found: C, 63.80; H, 5.03; N, 11.64.
~13~32
.
EXAMPLE 3: 6-(4-CHLOROPHENYLTHIO)-3-AMINOPYRIDINE
6-(4-Chlorophenylthio)-3-nitropyridine
(1.33 grams) was mixed with ammonium chloride t5.0
grams) in 5 ml. of water and about 50 ml. of 3A
ethanol at 70-80C. Iron powder (3.0 grams) was
added portionwise and the reaction mixture heated at
70-80C. with constant stirring, for 4 hours. The
solution was filtered hot, solvents were removed, and
the residue was washed with water; chloroform used to
extract the compound was removed in vacuo. A thick
oil was crystallized from ether-hexanes after passing
through a flush with ethyl acetate on silica gel.
The product precipitated as a white solid, yield 1.0
g., m.p. 55-57.
Calc. for CllHgClN2S: C, 55.81; H, 3.83; N, 11.83-
Found: C, 55.64; H, 3.82; N, 12.02.
EXAMPLE 4: 6-(4-CHLOROPHENYLTHIO)-3-AMINOPYRIDINE
6-Chloro-3-nitropyridine (54.5 grams),
4-chlorothiophenol (50.0 grams), and lithium hy-
droxide (12.5 grams) were mixed in about 500 ml. of
DMF and stirred overnight (about 18 hours) at room
temperature. The reaction mixture was poured into
ice-water, filtered, and the separated product washed
three times with water and air dried, yield, l00
grams.
.The product, withou~ purification, was
suspended in a mixture of 1 liter of 3A ethanol and
200 ml. of water. Ammonium chloride (400 grams) and
powdered iron (250 grams) were added and the reaction
.
il3~'~3;~:
--10--
mixture he~ted to reflux. The reaction became
exothermic and refluxed without external heat, for
one hour; external heat was supplied and the reaction
mixture was refluxed for another hour. The rea~tion
mixture was then filtered hot ~hrough Hyflo Super Cel
(a diatomaceous earth), extracted with ethyl acetate,
washed with water, and solvent removed, yield 58.0
grams. Identity of the product was confirmed by
compariso~ of the NMR with the NMR of an authentic
sample.
EXAMPLE 5: 6 (4-CHLOROPHENYLSULFONYL)-3-NITROPYRIDINE
Hydrogen peroxide (30%) was added portion-
wise at room ~emperature to a solution of 6-(4-
chlorophenylthio)-3-nitro~yridine (15.7 grams; 0.06
mole) in about 100 ~1. of acetic acid. The reaction
mixture was th~n stirred for 10 hours at 70C. TLC
showed 2 spots. Additional hydrogen peroxide was
added and the reaction mixture warmed slightly in a
water bath. The product precipitated and was
separated by filtration and crystallized from
ethanol, yield, 12.7 grams, m.p. 177-180C.
Calc. for CllH7ClN2O4S: C, 44.23; H, 2.36; N~ 9-38-
Found: C, 44.47; H, 2.29; N, 9.37.
EXAMPLE 6: 6-(3-(TRIFLUOROMETHYL)PHENYLSULFINYL)-3-
AMINOPYRIDINE
6-(3-(Trifluoromethyl)phenylthio)-3-
aminopyridine (4.0 grams) was dissolved in 50 ml. of
acetone and m-chloroperoxybenzoic acid (4.0 grams)
~3~Z
. .~ ..
added. The solution was allowed to stir at room
temperature for 2 hours, and an additional 1.0 gram
of m-chloroperoxybenzoic acid was added. The re-
action mixture was passed over a column of silica gel
with ethyl acetate, and the fraction corresponding to
the product collected and crystallized from ethyl
acetate-hexanes, yield, 4.0 grams m.p. 74-76C.
Calc. for C12HgF3N2OS: C, 50.35; H, 3.15; N, 9.79.
Found: C, 50.08; H, 3.31; N, 9.84.
10 EXAMPLE 7: 2,6-DICHLOROBENZOYL ISOCYANATE
A one-liter flask was purged with nitrogen
while dry 2,6-dichlorobenzamide (125 grams, 0.64
mole) and dry toluene (300 ml.) were added. The
nitrogen purge was continued as oxalyl chloride (100
grams, 0.79 mole) was added over a 15-minute period,
with stirring. The reaction mixture was then heated
to 55Co and stirred overnight (about 18 hours) at
55C~
The reaction mixture was then heated to
reflux (111C.) and refluxed for 2 hours. Solvent
was removed under vacuum and the product distilled
off at 134-135C. flask temperature and 131-132C.
vapor temperature, at 13 mm. vacuum, yield 127.5
25 grams (92. 5%) ~
Calc. for ClgH12C13N3O2S: C, 50.41; H, 2.67; N, 9.28.
Found: C, 50.54; H, 2.97; N, 9.45.
~.~3~23Z
-12-
EXAMPLE 8: 1-(2,6-DICHLOROBENZOYL)-3-(6-(4-CHLORO
PHENYLTHIO)-3-PYRIDINYL)UREA
2,6-Dichlorobenzoyl isocyanate (2.16 grams;
0.01 mole) and 6-(4-chlorophenylthio)-3-aminopyridine
(2.37 grams; 0.01 mole) were mixed in dry ethyl
acetate and stirred for 4 hours. The ethyl acetate
was removed in vacuo. TLC showed a 3-spot mixture.
The reaction mixture was then poured over a silica
column with ethyl acetate, and the major spot collected.
It was crystallized from ethyl acetate-hexanes, yield
1.5 g., m.p. 160-162C.
Calc. for ClgH12C13N302S: C, 50.41; H, 2.67; N, 9.28.
Found: C, 50.54; H, 2.97; N, 9 45.
15 EXAMPLE 9: 1-(2,6-DIMETHOXYBENZOYL)-3-(6-(4-CHLORO-
PHENYL~HIO)-3-PYRIDINYL)UREA
2,6-Dimethoxybenzoyl isocyanate (2.07
grams; 0.01 mole) and 6-(4-chlorophenylthio)-
3-aminopyridine l2.37 grams; 0.01 mole) were mixed in
100 ml. of ethyl acetate and stirred at room tem-
perature for 3 hours. Solvent was removed in vacuo
and the product crystallized from hexanes-ethyl
acetate, yield 0.6 gram, m.p. 172 174C.
Calc. for C21H~8ClN304S: C, i6082; H, 4.09; N~ 9.47.
Found: C, 56.66; H, 3.85; N, 9.64.
EXAMPLE 10: 1-t2,6-DIMETHOXYBENZOYL)~3-~6-(4-
BROMOPHENOXY)-3-PYRIDINYL)UREA
2,6-Dimethoxybenzoyl isocyanate (2.0 grams)
30 and 6-(4-bromophenoxy)-3-aminopyridlne (2.3 grams)
were mixed in about 50 ml. of ethyl aceta~e at room
~3~Z3;~
-13-
temperature, and the reaction mixture stirred over-
night (about 17 hours) at room temperature. The
product was separated by filtration and crystallized
from a mixture of ethyl acetate and ethanol, yield
0.9 gram, m.p., 177-179C~ -
Calc. for C21H18BrN3O5: C, 53.41; H, 3.84; N, 8.90.
Found: C, 53.19; H, 4.05; N, 9.02.
EXAMPLE 11: 1-(2,6-DIMETHYLBENZOYL)-3-(6-(4-
CHLOROPHENYLTHIO)-3-PYRIDINYL)UREA
2,6-Dimethylbenzoyl isocyanate (1.61 grams;
0.01 mole) and 6-(4-chlorophenylthio)-3-aminopyridine
(2.36 grams; 0.01 mole) were mixed in 50 ml. of ethyl
acetate and stirred at room tempèrature for 12 hours.
Solven~ was removed in vacuo. TLC showed four spots.
The mixture was passed over a column of silica gel
with a l:l mixture of toluene-ethyl acetate and the
product (Rf - .7) separated and crystallized from
ethyl acetate-hexanes, yield 1.1 grams, m.p. lS9-
160C.
Calc. for C21H18ClN3O2S: C, 61.23; ~, 4~40; N, 10.20.
Found: C, 61.48; H, 4.70; N, 10.34.
EXAMPLE 12: 1-(2,6-DICHLOROBENZOYL)-3~6-(4-
CHLOROPHENYLTHIO)-3-PYRIDINYL)UREA,
HYDROCHLORIDE SALT
1-(2,6-bichlorobenzoyl)-3~(6-(4-chloro-
phenylthio)-3-pyridinyl)urea (2.0 grams) was refluxed
in 100 ml. of concentrated HCl (37%) for 4 hours.
The reaction mixture was cooled and the product
separated by filtration, yield 1.5 grams, m.p.,
214-217C.
~3~LZ32
.
--14--
Calc. for ClgH13C14N3O25: C, 46.65; H, 2.68; N, 8.59.
Found: C, 46.90; H, 2.68; N, 8.44.
EXAMPLE 13~ 2-CEILORO3ENZOYL)-3- (6- (3- (TRIFLUORO-
METHYLPHENYLTHIO)-3-PYRIDINYL)THIOUREA
6- (3- (Trifluoromethyl)phenylthio)-3-
aminopyridine (1.0 gram) and 2-chlorobenzoyl iso-
thiocyanate (1.0 gram) were mixed in 50 ml~ of ethyl
acetate and stirred overnight (about 18 hours) at
10 room temperature. Solvents were then removed by
evaporation and the product residue was crystallized
from ethyl acetate-hexanes, m.p. 134-137C., yield
1.7 grams.
Calc. for C20EI13ClF3N3OS2: C, 51.34; H, 2.80;
N, 8.9~
Found: C, 51.35; H, 2.93;
~, 9~06
EXAMPLE 14: 2-NITRO-5-CHLOROPYRIDINE
2-Amino-5-chloropyridine (50 grams) was
20 added portionwise to a solution or 300 ml. of con-
centrated H2SO4 and 150 ml. of 30% H2O2, maintainedat a temperature of 0-5C., over a period of 5.0
hours. The reaction mixture was then allowed to rise
to room temperature and stirred at room temperature
25 for 24 hours. The reaction mixture was then poured
over ice, and the product residue separated by
filtratior~ and air dried. Crystallization from ethyl
acétate-ethanol gave only the azo compound. The
remainder of the product residue was passed over a
30 column of silica gel with a mixture of 1:1 toluene:-
~l 3:1232
-15-
eth~l acetate. The desired product was isolated and
its identity confirmed by NMR.
EX~PLE lS: 2-NITRO-S-(4-CHLOROPHENYLTHIO)PYRIDINE
2-Nitro-5-chloropyridine (9.S grams),
4-chlorothiophenol (8.7 grams), and lithium hydroxide
(4 grams) were mixed in 100 ml. of DMF and the
reaction mixture was stirred overnight (about 18
hours) at room temperature. The reaction mixture was
then poured into water and the produc~ separated by
filtration and crystallized from ethanol-hexanes,
yield, 10.0 grams, m.p., 96-98C.
Calc. for CllH7ClN2O2S: C, 49.54; H, 2.65; N, 10-50-
Found: C, 49.31; H, 2.88; N, 10.38.
EXAMPLE 16: 2-~MINO-5-(4-CHLOROPHENYLTHIO)PYRIDINE
2-Nitro-5-(4-chlorophenylthio)pyridine
(10.5 grams), ammonium chloride (50.0 grams), and
powdered iron (30.0 grams) were reacted in the same
procedures reported in Example 3. The reaction
mixture was filtered hot solvents were removed. The
product was extracted with e~hyl acetate, washed with
water, the ethyl acetate removed, and the product
crystallized from ethyl acetate-hexanes, yield 4.5
grams, m.p. 157-159C.
Calc. for CllHgClN2S: C, 55.81; H, 3.83; N, 11.83.
Found: C, 55.97; H, 3.88; N, 11.57.
EXAMPLE li: 2-AMINO-5-BROMOPYRIDINE
Bromine (240 grams) was added dropwise to a
solution of 2-aminopyridine (141 grams) in 1 liter of
1232
~ . . . .
~ .
-16-
acetic acid, maintaining the temperature at 0C.
After the completion of the addition, the ~emperature
of the reaction mixture was raised to 50C. and the
reaction mixture stirred for one hour at that tem~
perature, then poured into water. The precipitate
was separated by filtration, and the reaction mixture
neutralized with concentrated NaOH and a second
precipitate separated by filtration.
NMR established that the first precipitate
was 2-amino~3,5-dibromopyridine, whereas the second
precipitate was the desired 2-amino-5-bromopyridine,
yield, 100 grams, m.p., 130-132C. (lit. ref., Or~.
Svn. Coll. 5, supra, m.p., 132-135C).
-
EXAMPLE 18: 2-AMINO-5-(4-CHLOROPHENYLTHIO)PYRIDINE
2-Amino-5-bromopyridine (7.8 grams),
4-chlorothiophenol (9.2 grams), sodium methoxide (3.5
grams), and copper powder (1.0 gram) were reacted in
100 ml. of methanol, for 12 hours, in a bomb, in
accordance with ~he procedures of J. Med. Chem. 21,
235 (1978). The reaction mixture was filtered,
washed with methanol, and methanol removed by evap-
oration. The methanol washes were combined with
ethyl acetate extracts of solids made after refluxing
on a steam bath for one hour. Solvents were removed
and the solids dissolved in ethyl acetate and fil-
tered to remove insolubles. The liquid was passed
over a silica column with ethyl acetate, and the
fra~tion corresponding to the product amine (R~ -
300.2) collected., yield 6~5 grams, m.p., 161-163C.
~3~3~
Calc- for CllH9ClN2S C, 55.81; H, 3.83; N, 11.83.
Found: C, 55.87; H, 4.02; N, 11.83.
Other representative compounds of the
present invention include the following.
~13~LZ3Z
~1~ ! ,
_ o ,
~_ ~D -
~1 ~
~ S~ O
~O
~ O r~l
S
l l
I I
_ ~ I
I X X
I O O X
I ~ C Ç: O,
^ :~ -- S S ~I)
x~ o x
~ ~ o X '
C) ~ ~ O
S ~ ~ .C
'- Q~
:>~ X
X O X ,~
O ~ O ~ ~ -~
.C ~J .C I I
J~
a~
1 5 E~
.,~ ~ .,, _ _ ",
I ~ ~ ~ _
~ I In
Z
~ _
C
o
Q I
E~ ~ I 1'') N N O
20o ~ _ ~ c: ~ N
c~ ~
:~ O :>~ ~ ~ Q
O N O X X O
N ~ N O O h
~ .1 ~ O
C~ Q O ~
X ~ E~
O a) s ~ o ~
5~ I h
~. J S ~ O ~O 1 0 ~
C.~ ^ h--
~ ~ O ~O ~ O ~
~ a ~
I C I ~ I C S
_ ~ ~ h--
O
Z;
F~ L'l Ln U') ~)Il')li')
~ N ~I ~ ~ ~ ~
~i
3~Z3Z -,
--19--
The compounds of the present invention are
useful for the control of insects of various orders,
including Coleoptera such as ~e~ican bean beetle, boll
weevil, corn rootworms, cereal leaf beetle, flea -~
beetles, borers, Colorado potato beetle, grain
beetles, alfalfa weevil, carpet beetle, confused flour
beetle, pcwder post beetle, wireworms, rice weevil,
rose beetle, plum curculio, white grubs; Diptera, such
as house fly, yellow fever mosquito, stable fly, horn
fly, blowfly, cabbage maggot, carrot rust fly;
Lepidoptera, such as southern armvworm, codling moth,
..
cutworm, clothes moth, Indian meal moth, leaf rollers,
corn earworm, European corn borer, cabbage worm,
cabbage looper, cotton bollworm, bagworm, eastern tent
caterpillar, sod webworm, fall armyworm; and Ortho~tera,
such as German co~kroach and American cockroach.
The compounds of the present invention are
additionally useful for the control of other insects such
as common cattle grub, face fly, mosquitoes, spruce bud
worm, bollworms, tabanid fly~ tobacco budworm, armyworms
including beet armyworm ana yellow striped armyworm, South-
western corn borer, potato leafhopper, lesser cornstalk
borer, grasshoppers, cotton fleahopper, wheat stem sawfly,
horse fly, webworms, maggots, velvetbean caterpillar, pecan
weevil, whitefringed beetle, pecan nut casebearer, pink
bollworm, darkling beetle, hickory shuckworm, walnut cater
pillar, tobacco hornworm, loopers, Egyptian cotton leaf-
worm, co¢kroaches, green cloverworm, alfalfa caterpillar,
co'rn leaf beetle, leaf miner fly, diamondback moth,
rednecked peanut worm, stalk borer, cigarette beetle,
3~23~
-20-
sunflower moth, tomato pinworm, oriental fruit moth,
peachtree borer, melon fly, imported cabbase worm,
lesser peachtree borer, grape root borer, black fly,
pepper weevil, threestriped blister beetle, sunflower
beetle, nose bot fly, grape berry moth, sheep ked, and
leaf rollers.
It is believed that the present compounds
act by interfering with the mechanism of metamorphosis
which occurs in insects, causing the death of the
insects. It is also believed that ingestion by the
insects is necessary to invoke this mechanism. While
the death of any given insect may be delayed until
that insect reaches some stage of metamorphosis, the
net result of this activity is the control and
suppression of insects.
Therefore, in another embodiment, the
present invention is directed ~o a method of sup-
pressing insects which comprises applying to a locus
of the insects an effective amount of a compound of
the present invention. The locus can be any environ-
ment inhabited by insects to be controlled, such as
soil, air, water, foods, vegetation, manure, inert
objects, stored matter such as srain, and the like.
Preferably the compounds of the present
invention are supplied in a formulation, for ease of
application. The compounds can be formulated with
various adjuvants, including water, orsanic liquids,
surface-active agents, inert solids, and the like.
Sultable surface-active agents include anionic agents,
such as sodium lauryl sulfate, sodium dodecylbenzene-
~3~;Z3Z
)
.
-21-
sulfonate, and the like; and nonionic agents, such as
polyethylene glycol p-nonylphenyl ether. Mixtures are
often desirably employed. The formulation can take
the form of a liquid, dust, granule, aerosol, etc.
The formulation can be concentrated, as in a slow
release formulation or as in a formulation to be
diluted with water before application to the locus of
insects. Many methods of formulation are known in the
art and can be employed to implement the present
invention.
The concentration of active agent in the
formulation is not critical, inasmuch as an effective
concentration will vary with the nature of the locus
to be treated~ the severity of insect infestation, the
susceptibili~y of the particular insects involved,
etc. In general, concentrations ranging from about
0.1 to 1000 ppm give good results. As exemplified by
Table 2, below, lesser concentrations of from about 1
to about 100 ppm have given good control of southern
armyworm.
The insecticidal activity of the present
compounds was determined by testing the efficacy of
formulations of the compounds against Mexican bean
beetle larvae tEpilachna varivestis), and against
southern armyworm larvae (Spodoptera eridania). These
insects are members of the Coleoptera and Lepidoptera
orders of insects, respectively. The formulations
were applied to the foliage of plants and the larvae
werie subsequently permitted to feed on the foliage.
The compounds were tested in a plurality of concen-
trations, from a concentration of about 1000 ppm. to
about 1 ppm.
~L~3~Z32
-22-
Each compound to be tested was formulated by
dissolving 10 mg~ of the compound in 1 ml. of a
solvent made up with 23 grams of Toximul R and 13
srams of Toximul S per liter of 1:1 anhydrous ethanol
and acetone. Each of Toximul R and Toximul S is a
sulfonate/nonionic blend produced by Stepan Chemical
Company, Northfield, Illinois. Water was then added
to obtain 10 ml. of solution containing the compound
in a concentration of 1000 parts per million. Alter-
natively, 11 mg. of compound was used, to make up11 ml. of solution, of which 10 ml. was employed as a
1000 ppm. treating solution, and of which the re-
maining 1 ml. was diluted further with water to obtain
a treating solution containing 100 ppm. of compound.
Formulations of th~ compound at lesser concentrations
were prepared in the same manner, using the same
solvent.
Each solution of test compound was sprayed
onto two 4-inch square pots of bean plants containin~
6 to 10 plants per pot. The plants were allowed to
dry and then 12 leaves were removed and the cut ends
wrapped in water-soaked cellucotton. The leaves were
divided between six 100 x 20 mm. plastic petri dishes.
Five second-instar Mexican bean beetle larvae
(Epilachna varivestis) and five second- and third-
instar southern armyworm larvae ( ~ eridania)
were placed in each of three dishes. The dishes were
th~'n placed in a room wherein the temperature and
relative humidity were controlled at about 78F. and
about 51 percent, respectively, for a period of four
~3~23;2
-23-
days, at which time the first evaluation of the
effects of the test compounds was made. After this
evaluation, two fresh leaves from the orisinal treated
pots were placed in each dish. The dishes were again
maintained in the temperature and humidity controlled
room for an additional three days until the ~inal
seven-day evaluation was made.
Xnsecticidal effect was determined by
countins the number of living larvae of each species,
and applying the following rating code:
0 = all larvae livins
1 = half or more than half of the
larvae livins
2 = less than half of the larvae
living
~ 3 = all larvae dead
The results of this test are set forth in
Table 1, which follows. In the table, column 1
identifies the compounds by the number of the prep-
arative example; column 2 lists the concentration of
the test compound in the formulation; and columns 3
through 6 give the rating code at days 4 and 7 for the
two insects against which the compounds were tested.
~5
1~3'1Z32
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-25-
Many of the compounds of the present in-
vention were also tested in the same procedure
described above but at lower concentrations. In these
tests, percent control was determined by counting the
number of living larvae per dish and using Abbott's
formula [W. W. Abbott, "A Method of Computing the
Effectiveness of an Insecticide", J. Econ. Entomol.
18, 265-7 (1925)]:
Percent Control =0 No. of survivors in control - No. of survivors in
treatment x 100
No. survivors in control
The results are set forth in Tables 2A and 2B,
which follow.
,
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