Note: Descriptions are shown in the official language in which they were submitted.
~IL298~
NOVEL l-(MONO~ -SUBSTITUTED BENZOYL)-3-
(SUBSTITUTED PYRAZINYL.)URE'.AS
The control of insects is of vital importance in
the increasingly populous world of today. It i.; we.ll known
that insects such as those belonging to the orders of
Lepidoptera, Coleoptera, Diptera, Homoptera, Hemip-tera and
Orthoptera, at the larval stage, cause extensive damage to
many crops, for example, food crops and fibrous crops.
Control of such insects contributes to the well-being of
mankind by increasing the supplies of food and o~ the
fibrous materials useful in the production o~ clothing~
In the ,prior art, Wellinga et al., U.S. 3,748,356
(July 24, 1973), describe a series of substitutel benzoyl-
ureas which are taught as having strong insecticidal ac-
tivity. These compounds are generally 1-(2t6-dichloro-
benzoyl)-3-(substituted phenyl)ureas, but also include
several 1-(2,6-dichlorobenzoyl)-3-(substituted pyridyl)-
ureas.
Also in the prior art, Wellinga et al., U.S.
3,989,842 (November 2, 1976), teach and claim insecticidal
compositions and a method of controlling insects in agri-
culture and horticulture utilizing certain N-(2,6-dihalo-
benzoyl)-N'-(substituted phenyl)urea compounds as the active
ingredient, as well as several N-(2,6-dichlorobenzoyl)-
N'-(substituted pyridyl)ureas.
Other N-(2,6-dihalobenzoyl)-N'-(substituted
phenyl)urea compounds are disclosed and claimed in Wellinga
et al., U.S. 3,933,903 (January 20, 1976), which compounds
are disclosed as having insecticidal activity.
X-5051 -2-
~.:1298~1
A number of prior art references discuss the
insecticidal activity o~ 1-(2,6--dichlorobenzoyl)-3-(3,4-
dichlorophenyl)urea. See Van Daalen et al., Die
Naturwissenschaften 59, 312-313 (1972); Post et al., ibid.
60, 431-432 (1973); Mulder et al., Pestic. Sci. 4, 737-745
(1973).
Also, studies in the inhibition of -the development
of mosquitoes and houseflies, and of the control of alfalfa
weevil, by the action of l-(4-chlorophenyl)-3-(2,6-difluoro-
benzoyl)urea are reported by Jakob, J. Med. Ent. 10.
452-455 (1973), and Neal, Jr., J. Econ. Ent., 67, 300-301
(1974), respective~ly.
Yet another prior art reference is Sirrenberg et
al., U.S. 3,992,553 (November 16, 1976), which discloses and
claims mono-o-chloro-substituted benzoylureido-diphenyl
ethers, alleged to posses excellent insecticidal activity
against plant pests and as ectoparasitic agents in the
veterinary medicine field.
Also in the prior art is Belgian Patent No.
833,288 (March 11, 1976), which teaches and claims disub-
stituted benzoyl pyrazinylureas having activity as insecti-
cides.
Still another prior art reference is Belgian
Patent No. 838,286, directed to 1-benzoyl-3-(4-phenoxy-
phenyl)ureas alleged to possess insecticidal activity with
low mammalian and plant toxicity.
X-5051 -3-
~:3129~
The present invention relates to novel l-(mono-
o-substituted benzoyl)-3-(substi.-tuted pyrazinyl)ureas of the
formula
0 ~ /R (I)
--C - N - C - N -
wherein
A is bromo, chloro, or methyl;
Rl is hydrogen, halo, C3-C6 cycloalkyl, halo-
(Cl-C4)alkyl, nitro, cyano,
2 n \ ~ ' -X- D~
O--=0 0=~
R is hydrogen, halo, methyl, ethyl, cyano, or
halo(Cl-C2)a1kyl;
with the limitation that Rl and R2 may not both be
hydrogen at the same time;
R is hydrogen, halo, halo(Cl-C4)alkyl, Cl-C6
alkyl, Cl-C4 alkoxy, Cl-C~ alkylthio, Cl-C4 alkylsulfinyl,
Cl-C4 alkylsulfonyl, nitro, cyano, phenoxy, or phenyl;
m is 0, 1, 2, or 3;
n is 0 or 1; and
O O
.. ..
X is -O-, -S-, -S-, or -S-.
O
The compounds of formula I are prepared by pro-
viding a ureido bridge between compounds of the formulae
X-5051 _4_
~L~29~
~ ---C--R4 and R5~-~
when reacted together wherein R4 a~d R5 are amino or iso-
cyanate; followed by oxidation when X is -S- when the com-
O O
.. ..
pounds of formula I are desired wherein X is -S- or -S-.
..
Preferred compounds coming within the scope of
formula I above are those wherein
A is bromo, chloro, or methyl;
Rl is hydrogen, halo, C3-C6 cycloalkyl, halo-
(Cl-C4)alkyl,
~---~Rm o-~Rm
-(CH ) --o~ ~ , -X---\ /a ~ or naphthyl;
R is hydrogen, halo, methyl, ethyl, or halo-
(Cl-C2)alkyl;
with the limitation that Rl and R2 may not both be
hydrogen at the same time;
R3 is halo, halo(Cl-C4)alkyl, Cl-C6 alkyl, Cl-C4
alkoxy, Cl-C4 alkylthio, Cl-C4 alkylsul~inyl, Cl-C4 alkyl-
sulfonyl, nitro, or cyano;
m is 0, 1, 2, or 3;
n is 0 or 1i and
O O
.. ..
X is -O-, -S-, -S-, or -S-.
o
X-5051 -5-
~Z98~
The more preferred compounds coming within the
scope of the above formula I are those wherein
A is bromo, chloro, or methyl;
Rl is halo, halo(Cl~C2)alkyl, C3-C6 cycloalkyl,
R3 R3
-X~ or -(CH )n~~~
R2 is hydrogen, halo, halo(Cl-C2)alkyl, or methyl;
R3 is hydrogen, halo, halo(Cl-C2)alkyl, Cl~C2
0 alkyl, or Cl-C2 alkoxy;
m is 0, 1, or 2;
n is 0 or 1; and
X is -0- or -S-.
The most preferred compounds coming within the
scope of the above formula I are those wherein
A is bromo, chloro, or methyl;
Rl is -(CH2)n---~ ~ or cyclohexyl;
R is halo, halo(Cl~C2)alkyl, Cl-C2 alkyl, or
0 Cl-C2 alkoxy;
n is 0;
m is 1 or 2;
R is hydrogen or methyl; with the proviso that
when R2 is H, and m is 1, R3 must be chloro or bromo in the
para position.
In formula I above, halo refers to fluoro, chloro,
and bromo.
X-5051 -6-
1~6~
C3-C6 Cycloalkyl represents saturated cycloalkyl
having from 3 to 6 carbon atoms in the ring and is exempli-
fied by cycl~propyl, cyclobutyl, cyclopentyl an~ cyclohexyl.
Halo(Cl-C4)alkyl represents, for example, tri-
fluoromethyl, bromomethyl, l,l-difluoroethyl, pentafluoro-
ethyl, 1,1,2,2-tetrafluoroethyl, chlorodifluoromethyl,
trichloromethyl, 2-bromoethyl., chloromethyl, 3-bromopropyl,
4-bromobutyl, 3-chloropropyl, and 3-chlorobutyl.
~ alo(Cl-C2)alkyl refers to, for example, tri-
fluoromethyl, bromomethyl, chloromethyl, l,l-difluoroethyl,
pentafluoroethyl, l,1,2,2-tetrafluoroethyl, chlorodifluoro-
methyl, trichlorom~ethyl, and 2-bromoethyl.
Cl-C2 Alkoxy represents methoxy or ethoxy.
Cl-C4 Alkoxy represents methoxy, ethoxy, propoxy,
isopropoxy, n-butoxy, sec.-butoxy, isobutoxy, or t-butoxy.
Cl-C2 Alkylthio represents methylthio or ethyl-
thio.
Cl-C4 Alkylthio represents methylthio, ethylthio,
n-propylthio, isopropylthio, n-butylthio, isobutylthio,
sec.-butylthio, or t-butylthio.
Cl-C4 Alkylsulfonyl represents, for example,
methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, iso-
propylsulfonyl, and butylsulfonyl.
Cl-C4 Alkylsulfinyl represents, for examplP,
methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, iso-
propylsulfinyl, and butylsulfinyl.
Novel compounds coming within the scope of
formula I above include, but are not limited to the fol-
lowing:
X-5051 _7_
~Li29~3G~L
1-(2-Bromobenzoyl)-3-[5-(a,a,-trifluoro-m-
tolyl)~6-methyl-2-pyrazinyl~urea
1-(2-Methylbenzoyl)-3 [5-(a,a,a-trifluoro-~-
tolyl)-6-methyl-2-pyrazinyl]urea
l-[S-(a,a,a-trifluoro-m-tolyl)-2-pyrazinyl]-3-
(2--chlorobenzoyl)urea
1-(5-Chloro-6-methyl-2-pyrazinyl)-3-(2-chloro-
benzoyl)urea
1-(5-Bromo-6-ethyl-2-pyrazinyl)-3-(2-methyl-
benzoyl)urea
l-(?-Bromobenzoyl)-3-[5-(a,a,a-trifluoro-~-
tolyl)-2-pyrazinyl~urea
1-(6-Bromo-5-cyano-2-pyrazinyl)-3-(2-chloro-
benzoyl)urea
1-(5-Cyclopentyl-6-methyl-2-pyrazinyl)-3-(2-
methylbenzoyl)urea
l-[S-(2-Bromoethyl) 2-pyrazinyl]-3 ~2-bromo-
benzoyl)urea
1-(5-Benzyl-6-chloro-2-pyrazinyl)-3-(2-methyl-
benzoyl)urea
1-(2-Chlorobenzoyl)-3-(5-phenylthio-2-pyrazinyl)
urea
1-(2-Bromobenzoyl)-3-(6-methyl-5-benzyl-2-
pyrazinyl)urea
1-(2-Chlorobenzoyl)-3-[5-(1-naphthyl)-2-pyrazinyl]-
urea
1-(2-Chlorobenzoyl3-3-(6-cyano-5-phenyl-2-
pyrazinyl)urea
1-(2-Chlorobenzoyl) 3-(5-nitro-2-pyrazinyl)urea
~-5051 -8-
1-(2-Chlorobenæoyl)-3-[5-(4-chlorophenylkhio)-
6-methyl-2-pyrazinyl]urea
1-(2-Methylben~oyl)-3-[5-(4-bromophenoxy)-2-
pyrazinyl~urea.
The novPl compounds o~ ~ormula I have been found
to be active as insecticides by their action in interfering
with the growth of sensitive insects. The comp~unds appear
to interfere with the molting process of the insects and
thus cause death. The compounds have been found to act on
the insects as a result of the insects ingesting the com-
pounds, e.g., by ingesting the leaves and foliage treated
with the active cpmpounds~ or ingesting any other part of
their normal habitat, e.g., water, manure, and other
similar carriers, to which the active compounds have been
applied. Because of this property, the compounds are useful
in a novel method of controlling insects at the larval
stage.
The novel compounds of formula I unexpectedly and
surprisingly show systemic activity in plants to which the
compounds are applied. Thus, when one of the novel in-
secticidal compounds is applied to an old leaf on a plant,
such as a soybean plant, it is foun~ the insecticidal
compound is translocated in the soybean plant to the new
growth of the plant, and even down the main stem of the
plant. However, there is no systemic translocation of the
insecticidal compound if the compound is applied to the
roots of the soybean or other plant.
3~
X-5051 -9-
6~
Further it has been found that compounds coming
within the scope of formula I, and having ovicidal activity
are those wherein
A is bromo or chloro;
Rl is hydrogen, trifluoromethyl, or
2 n \ __ ~
R2 is hydrogen, chloro, methyl, or tri~luoro-
methyl;
R3 is hydrogen, halo, methoxy, trifluoromethyl, or
phenyl;
m is 0 ~or 1; and
n is 0.
The novel compounds of formula I are prepared by
analogous procedures known to the artO
The novel compounds of formula I are prepared by
allowing the 2-aminopyrazine intermediate compounds to react
with a 2 substituted-benzoyl isocyanate to yield the corre-
sponding l-(mono-_-substituted benzoyl)-3-(substituted
pyrazinyl)urea. The reaction is carried out at a tempera-
ture of from about 0 to about 70C~, suitably at about room
temperature, for a sufficient period of time to bring about
substantial completion of the reaction. Such time of
reaction appears to depend on the particular reactants and
can range from the time during which one of the reactants is
added to and mixed with the other to 48 hours. The reaction
is carried out using a suitable solvent. A suitable solvent
is one which is inert to and will not react with the
isocyanate compounds used in any of these reactions.
X-5051
~2~
Exemplary solvents include, but are not limited to ethyl
acetate, dimethylformamide, tetrahydrofuran, dioxane,
acetonitrile, benzene, toluene, chloroform, or methylene
chloride. The preparation is exemplified as follows:
2-chlorobenzoylisocyanate is allowed to react with 2~
amino-5-(4 bromophenyl)-6-methylpyrazine in cold ethyl
acetate. The reaction mixture is stirred overnight at room
temperature. The product is isolated by filtering, and is
purified by recrystallization from a suitable solvent such
as ethanol. There is obtained a product having a melting
point of about 230-232C., which product is identified by
elemental analysçs and NMR and infrared spectra as 1-
(2-chlorobenzoyl)-3-[5-(4-bromophenyl-6-methyl-2-pyrazinyl]-
urea.
A compound of formula I may also be prepared by
allowing a 2-substituted benzamide to react with a 2-
pyrazinylisocyanate utilizing the appropriate solvents,
times of reaction and general reaction conditions herein
above described. For example, 2-chlorobenzamide is allowed
to react with 5-trifluoromethylpyrazin-2-ylisocyanate to
yield 1-(2-chlorobenzoyl)-3-(5-trifluoromethyl-2-pyrazinyl)-
urea, having a melting point of about 219-220C.
Some of the starting materials are commercially
available, others are prepared by utilizing procedures which
are known to the art.
The 2-substituted-benzoylisocyanates are readily
prepared from, for instance, 2-substituted benzamides,
following the general procedure of Speziale et al., J. Or~.
Chem. 27, 3742 (1962)~ -
~-5051
36~
One of the intermediates, 2-amino-5-chloropyrazine
is prepared following the general procedure of Palamidessi
and Bernardi, J. Org. Chem. 29, 2491 (1964), wherein methyl
2-amino-3-pyrazinylcarboxyla-te is allowed to react ~ith
chlorine in acetic acid to yield methyl 2-amino-5-chloro-
3-pyrazinylcarboxylate. This ester is hydrolyzed with
aqueous sodium hydroxide to yield 2-amino-3-carboxy-5-
chloropyrazine, which is then heated in tetrahydronaphthalene
and decarboxylated to yield the desired 2-amino-5-chloro-
pyrazine.
Another intermediate, 2-amino-5,6-dichloro-
pyrazine, is prepa~ed by allowing 2-amino-6-chloropyrazine
to react with N-chlorosuccinimide in chloroform to yield a
mixture of 2-amino-5,6-dichloropyrazine, 2-amino-3,6-
dichloropyrazine, and 2-amino-3,5,6-trichloropyrazine. The
mixture is then separated by column chromatography and the
desired 2-amino-5,6-dichloropyrazine is obtained.
The 2-amino-5-phenylpyrazine necessary for this
~ork is prepared according to the procedure of Lont et al.,
Rec. Trav. Chim. 92, 455 (1973), and references therein.
Other 2-amino-5(or 6)-substituted pyrazines useful
in preparing the novel compounds of formula I are prepared
utilizing oxime derivatives of certain ketones. Oxime
intermediates are prepared from such ketones as acetophenone,
4-trifluoromethylacetophenone, 4-fluoroacetophenone, 2,4-
dimethylacetophenone, 4-_-butylacetophenone, 4-chloro-
acetophenone, and m-trifluoromethylacetophenone, following
the general procedure of Claisen et al., Chem. Ber. 20, 2194
(1887~. Still other oxime intermediates are prepared from
X-5~51 -12-
86~L
ketones such as 4-methoxypropiophenone, 4-trifluoromethyl-
propiophenone, 4-fluoropropiophenone, 4-n-butylpropiophenone,
4-bromobutyrophenone, and 4-bromopropiophenone, following
the general procedure of Har~ung et al., J. Am. Chem~ Soc.
51, 2262 ~1929).
Another intermediate pyrazine compound, 2-
amino-5-(4-bromophenyl)-6-methylpyrazine, is synthesized
starting with l-(4-bromophenyl)-1,2-propanedione 2-oxime,
which oxime is obtained by the same general procedure of
Hartung et al., supra. This oxime is allowed to react with
aminomalononitrile tosylate, and the product, the substituted
pyrazlne l-oxide, ~s allowed to react with phosphorus tri-
chloride in tetrahydrofuran, according to the procedure ~f
Taylor et al., J. Org. Chem. 38, 2317 (1973), to yield
2-amino-3-cyano-5-(4-bromophenyl)-6-methylpyrazine. This
product is then hydrolyzed in sodium hydroxide and ethylene
glycol and the 2-amino-3-carboxy-5 (4-bromophenyl)-6-
methylpyrazine so obtained is decarboxylated by heating in
tetrahydronaphthalene to yield 2-amino-5-(4-bromophenyl)-
6-methylpyrazine.
Still other pyrazine intermediate compounds can he
prepared starting with 2,5-dichloropyrazine, which itself
can be prepared by the procedure of Palamidessi and Bernardi,
J. Org. Chem. 29, 2491 (1964). This 2,5-dichloropyraæine
can be used as the starting material for the phenoxy,
phenylthio, phenylsulfinyl, or phenylsulfonyl substituted
pyrazine intermediates, or the corresponding substituted-
phenoxy, substituted-phenylthio, or substituted-phenyl-
sulfonyl-substituted pyrazine intermediates. Thus, as a
X-5~51 -13-
86~
general proce~ure, 2,5-dichloropyrazine can be allowed to
react with an equivalent of phenoxide or thiophenoxide ion
in a suitable solvent such as ethanol, t-butanol, dimethyl-
formamide, or acetonitrile, at a temperature in the range of
from about 0 to about 120C., to yield the corresponding 2-
chloro-5-phenoxy(or phenylthio)pyrazine. The 2-chloro-
5-phenoxy(or phenylthio)pyrazine can be converted to the
corresponding 2-amino-5-phenoxy(or phenylthio)pyrazine by
reaction with ammonium hydroxide at a temperature in the
range of about 150-200C. in a high pressure reaction vessel
for a time sufficient to give substantially complete
conversion. The 2,amino-5-phenoxy(or phenylthio)pyrazine
obtained in this manner can then be used to prepare the
1-(mono-o-substituted benzoyl)-3-[5-phenoxy(or phenylthio)-
2-pyrazinyl]ureas. Substituted phenoxy- or phenylthio
compounds can be pxapared in the same general manner.
The 2-chloro-5-phenylthiopyrazine intermediate, or
homologue thereof, can be oxidized to the 2-chloro-5-
phenylsulfinylpyrazine or the 2-chloro-5-phenylsulfonyl-
pyrazine intermediate through the use of such oxidizingagents as peracetic acid or m-chloroperbenzoic acid.
Suitable solvents for use in carrying out this reaction
include acetic acid, chloroform, or methylene chloride.
Suitabl~ reaction temperatures for the o~idation can range
from about 20 to about 70C.
The 2 chloro-5-phenylsulfonylpyrazine or 2-
chloro-5-phenylsulfinylpyrazine can then be allowed to react
with ammonia or ammonium hydroxid~ in a high pressure
reaction vessel, at a temperature of about 100 to about
X-5051 -14-
~2986~
200C. to ~ield the 2-amino-5-phenylsulfonyl- or -sulfinyl-
pyrazine intermediate. Reaction conditions may ~ary depending
on the chemic~l structure of the phenylsulfonyl or phenyl-
sulfinyl grouping.
The preparations o~ the intermediate substitut~d
benzoylisocyanates and pyrazines are illustrated by the
following Preparations.
Preparation 1
2-Chlorobenzoylisocyanate
This compound was prepared following the procedure
of Speziale et al, J. ~. Chem. 27, 3742 (lg62).
A soluti~n of 10 g. of 2-chlorobenzamide (com-
mercially available) in lO0 ml. of methylene dichloxide was
prepared. Twenty-five ml. of oxalyl chloride was added very
slowly to the solution. The mixture was refluxed overnight.
The reaction product mixture was cooled and filtered and the
filtrate evaporated to remove the solvent, methylene di-
chloride. The oily residue was identified by infrared
spectrum as 2-chlorobenzoylisocyanate, and was used without
purification in preparing the novel compounds of formula I.
Following the same general procedure of ~rep-
aration 1, and starting with 2-methylbenzamide or 2-bromo-
benzamide, both of which compounds are commercially avail-
able, the following additional compounds were prepared and
identified by their IR spectra:
2. 2-Methylbenzoylisocyanate, as an oil.
3. 2-Bromobenzoylisocyanate, as an oil.
X-5051 -15-
~2986~L
Preparation _
2-Amino-5 chloropyrazine
This compound was prepared stepwise. The firsk
step followed the procedure of Dallacker et al., Ann. 660,
98-103 (1962).
Following that procedure, a mixture of 7.5 g. of
2-amino-3-carboxypyrazine, 8.9 g. of 1-methyl-3-~-tolyl
triazene, and 250 ml. of tetrahydrofuran was refluxed for
about 4 hours. The reaction product mixture was cooled and
filtered and the solid on the filter discarded. The fil-
trate was concentrated in vacuo to dryness and a small
amount of ethyl eth,er was added to the residue. The solid
which separated was collected. It weighed about 7 g. and
had a melting point of about 166-169C. It was identified
by infrared spectrum as methyl 2-amino-3-pyrazinylcarboxylate.
In the next step, a mixture of 2.8 g. of methyl
2-amino-3-pyrazinylcarboxylate, 100 ml. of water, and 23 ml.
of glacial acetic acid was stirred at a temperature of about
40C., and anhydrous chlorine bubbled through the mixture
for about 25 minutes, while maintaining the temperature of
the reaction mixture at about 35-40C. The reaction product
mixture was cooled and filtered. The solid obtained was
stirred for an hour in a mixture of 30 ml. of water and
4.6 g. of sodium sulfite, and filtered off. The solid which
was collected was stirred in a mixture of ice and water and
filtered offO The solid was identified by its NMR spectrum
as methyl 2-amino-5-chloro-3-pyrazinylcarboxylate. The
material was used without further purification.
X-5051 -16-
'' 3L~L2~S38~
E'ollowing the procedure of Palamidessi and
Bernardi, J. Org. Chem. 29, 2491 (1964), the methyl 2-
amino-5-chloro-3-pyrazinylcarboxylate was first hydrolyzed
and then decarboxylated.
A mixture of 1.6 g. of methyl 2-amino-5-chloro-
3-pyrazinylcarboxylate and 50 ml. oE 2N aqueous sodium
hydroxide was refluxed for about 1.5 hours. The reaction
product mixture was cooled and filtered. The solid which
was collected was dissolved in 25 ml. of hot water, the
solution filtered, and the filtrate acidified with con-
centrated aqueous hydrochloric acid. The solid which
separated was filte,red off and dried. It weighed 1.3 g.,
had a melting point of about 177C. (dec.), and was iden-
tified by its infrared spectrum as 2-amino-3-carboxy-
5-chloropyrazine. It was used without further purification.
A mixture of 500 mg. of 2-amino-3-carboxy-5-
chloropyrazine and 9 ml. of tetrahydronaphthalene was
refluxed for about 1 hour. The reaction product mixture was
cooled and filtered. The solid which was collected was
washed with hexane. The solid had a melting point of about
121-123C. (dec.), and was identified by NMR spectrum as
2-amino-5-chloropyrazine.
Preparation 5 `
2-Amino-5,6-dichlor_pyrazine
A mixture of 5 g. of 2-amino-6~chloropyrazine
(commercially available), 10.3 g. of N-chlorosuccinimide,
and 100 ml. of chloroform was refluxed for about lo 5 houxs.
The reaction mixture was cooled and filtered, the solid
collected on the funnel being discarded. The filtrate was
X-5051 -17-
29~6~
evaporated and the residue washed with water and hot aqueous
sodium bisulfite solution, and the solid which formed under
this treatment was collected on a funnal. The solid was
chromatographed on a column of 5 x 8 mm. styrene and divinyl-
benzene copolymer beads using chloroform as solvent and
eluant. There were obtained by this chromatography three
compounds:
Compound 1, having a melting point of about
132-135C., was identified as 2-amino-3,6-dichloropyrazine.
Compound 2, having a melting point of about ~ -
132-134C., was identified as 2 amino-3,5,6-trichloro-
pyrazine.
Compound 3, having a melting point of about
143-144C., was identified as 2-amino-5,6-dichloropyrazine,
the desired compound.
Preparation _
2-Amino-5-phenyl-6-methylpyrazine
This intermediate pyrazine was prepared via a
stepwise procedure.
In the first step, a mixture of 6.5 g. of 1-
phenyl-1,2-propanedione-2-oxime (commercially available) and
10.1 g. of aminomalononitrile tosylate in 60 ml. of iso-
propyl alcohol was stirred overnight at room temperature.
The reaction product mixture was filtered. The solid which
was collected weighed 7 g. The solid was identified by NMR
spectrum as 2-amino-3 cyano-5~phenyl-6-methylpyrazine
l-oxide.
~-5051 -18-
36:~L
A mixture of 7 g. of the pyra~ine l-oxide (pre-
pared above) and 250 ml. of tetrahydrofuran was cooled to
about 0C., and 40 ml. of phosphorus trichloride was added
slowly thereto. After addition w~s complete, the reaction
mixture was stirred overnight at room temperature. The
mixture was then concentrated ~n vacuo to a volume of about
50 ml., and the concentrate poured into one liter of a
mixture of ice and water. The solid which precipitated was
collected on a filter. The solid weighed 1 gram and was
identified as 2-amino-3-cyano-5-phenyl-6-methylpyrazine.
In the next step, a mixture of 1 g. of the 2-
amino-3-cyano-5-phsnyl-6-methylpyrazine (prepared above), 50
ml. of ethylene glycol, and 500 mg. of sodium hydroxide was
heated at about 150C. for about 3 hours. The reaction
product mixture was cooled, water was added r and the mixture
neutralized to a pH of 5-7. The solid which precipitated
was collected, and was identified by IR spectrum as 2-
amino-3-carboxy-5-phenyl-6-methylpyrazine. This solid was
used in the next step of the preparation.
The carboxypyrazine (prepared above), S00 mg., was
refluxed in 5 ml. of tetrahydronapthalene for about 2 -
hours. The reaction product mixture was cooled and hexane
added thereto. The solid which precipitated was filtared
off. It weighed 470 mg., and was identified by NMR and IR
spectra as 2-amino-5-phenyl-6-methylpyrazine.
Following the same general procedure described in
Preparation 6, and using as starting materials the indicated
oximes, p'repared as described by Hartung et al., J. Am.
Chem. Soc. _, 2262 (1929,, additional pyrazine intermed-
X-5051 -19-
~ ~ - ~ -
98~
iates were prepared. These pyrazine intermediates were
identified by NMR and IR spectra:
7. 2-Amino-5-(4-methoxyphenyl)-6-methylp~razine,
from 1-(4-methoxyphenyl)-1,2-propanedione-2-oxime.
8. 2-Amino-5-(4-chlorophenyl)~6-methylpyrazine,
from 1-(4-chlorophenyl)-1,2-prop~nedione-2-oxime.
9. 2-Amino-5-(4-bromophenyl)-6-methylpyrazine,
from 1-(4-bromophenyl)-1,2-propanedione-2 oxime.
10. 2-Amino-5-(4-_-butylphenyl)-6-methylpyrazine,
from 1-(4-n-butylphenyl)-1,2-propanedione-2-oxime.
11. 2-Amino-5-(a,a,a-trifluoro-_-tolyl)-6-methyl-
pyrazine, from l-~a,a,a-trifluoro-m-tolyl)-1,2-propane-
dione-2-oxime.
12. 2-Amino-5-(4-biphenylyl)-6-methylpyrazine,
from l-(4-biphenylyl)-1,2-propanedione-2-oxime.
13. 2-Amino-5-(4-fluorophenyl)-6-methylpyrazine,
from l-(4-fluorophenyl)-1,2-propanedione-2-oxime.
14. 2-Amino-5-(a,a,a-trifluoro-p-tolyl)-6-methyl-
pyrazine, from l-(a,a,a-trifluoro-p-tolyl)-1,2-propane-
dione-2-oxime
15. 2-Amino~5-(4-ethylphenyl)-6 methylpyrazine,
from l-(4-ethylphenyl)-1,2-propanedione-2-oxime.
16. 2-Amino-5-cyclohexyl-6-methylpyrazine from
l-cyclohexyl-1,2-propanedione-2-oxime.
17. 2-Amino-5-(4-methylthiophenyl)-6-methyl-
pyrazine, from 1-(4-methylthiophenyl)-1,2-propanedione-2-
oxime.
18. 2-Amino-6-methyl-5~(p-tolyl)pyrazine, from 1-
(~-tolyl)-1,2-propanedione-2-oxime.
X-5051 -20-
98~
Following the same general procedure described in
Preparation 6, and using oximes prepared by the method of
Claisen et al., Chem. Ber. 20, 2194 (1887), the following
additional pyrazine intermediates were prepared, and iden-
tified by NMR and IR spectra:
l9. 2-Amino-5-(2,4-xylyl)pyrazine, from 2,4-
xylylglyoxal oxime.
20. 2-Amino-5-(3,4-dichlorophenyl)pyrazine, from
3,4-dichlorophenylglyoxal oxime.
21. 2-Amino-5-(a,a,a-trifluoro-m-tolyl)pyrazine,
from 3-trifluoromethylphenylglyoxal oxime.
22. 2-Am,ino-5-(p-tolyl)pyrazine, from p-tolyl-
glyoxal oxime.
23. 2-Amino-5-(4-chlorophenyl)pyrazine, from
4~chlorophenylglyoxal oxime.
24. 2-Amino-5~(4-ethylphenyl)pyrazine, from 4-
ethylphenylglyoxal oxime.
25. 2-Amino-5-(4-t-butylphenyl)pyrazine, from
4-t-butylphenylglyoxal oxime.
26. 2-Amino 5-(4~bromophenyl)pyrazine, rom 4
bromophenylglyoxal.
Preparation 27
2-Amino-5-(4-bromophenyl)-6-ethylpyrazine
This intermediat~ pyrazine was prepared stepwise.
Using 4-bromobutyrophenone as starting material,
and following the procedure of Hartung et Al ., supra, there
was prepared l-(4-bromophenyl)-1,2-butanedione 2-oxime,
identified by IR and NMR spectrum.
X-5051 -21-
~29~6~
Following the genexal procedure of Preparation 6,
the l-(4-bromophenyl)-1,2-butanedione 2-oxime was used to
prepare 2-amino-5-(4-bromophenyl)-6-e-thylpyrazine, iden-
tified by IR and NMR spectrum.
Preparation _
2-Amino-6-cyanopyraæine
This intermediate was prepared via a stepwise
procedure.
A mixture of 21 ~. of pyrazine-2-carboxamide,
85 ml. of glacial acetic acid, and 75 ml. of 30 percent
hydxogen peroxide was heated at about 55C. for about 35
hours. The reactio,n product mixture was cooled and filtered.
The solid which was collected was extracted with n-butanol
and the extracts discarded. The solid which was insoluble
in n-butanol was recrystallized from hot water to yield a
white solid having a melting point of about 302-305C. The
solid was iden-tified by elemental analyses as pyrazine-
2-carboxamide 4-oxide.
To a mixture of 4 g. of the pyrazine oxide (pre-
pared above) in 40 ml. of dimethylformamide cooled in an icebath, there was quickly added 12 ml. of phosphorus oxy-
chloride. The reaction mixture was poured into water and
the aqueous mixture extracted with ethyl acetate, and the
extracts saved. Additional water was added to the aqueous
layer and the aqueous mixture extracted with hexane-ether.
The ethyl acetate and hexane-ether extracts were combined
and concentrated in vacuo to leave a residue. The residue
was identified by elemental analyses and IR spectrum as 2-
chloro-6-cyanopyrazine, and was used without further puri-
30 fication in the next step.
X-5051 22-
~2~P
A mixture of 1 g. of the above chlorocyanopyrazine
and 25 ml. of dimethyl sulfoxide was prepared and anhydrous
ammonia was bubbled thereinto. The reaction mixture was
stirred overnight and then poured into water. The aqueous
mixture was extracted with ethyl acetate, and the extracts
dried. The drying agent was filtered off and the solvent
r~moved ln vacuo to leave a solid which was identified by
its IR spectrum as 2-amino-6-cyanopyrazine. It was used as
is without further purification in the preparation of com-
pounds of formula I.
Preparation 29 1-
2-Amino-6-trifluoro~ethylpyrazine
This intermediate compound was prepared stepwise.
Aminoacetamidine dihydrobromide was prepared and
identified according to the procedure of Mengelberg, Chem.
Ber. 89, 1185 (1956). The prepaxation of 3,3-dibromo-
l,l,l-trifluoropropanone was accomplished according to the
procedure of McBee and Burton, J. Am. Chem. Soc. 74, 3902
(1952).
A mixture of 6.6 g. of 3,3-dibromo-1,1,1-tri-
fluoropropanone, 60 ml. of water, and 6.6 g. sodium acetate
was refluxed for about 10 minutes. The solution thus
obtained was cooled and added dropwise to a solution of 6 g.
of aminoacetamidine dihydrobromide in 90 ml. of methanol
cooled to a temperature of about -30C., followed by the
addition of a solution of 3.6 g. of sodium hydroxide pellets
in 25 ml. of water. The reaction mixture was stirred and
warmed gradually to about 20C. over a period of about two
hours. The reaction product mixture was concentrated ln
X-5051 -23-
86~
vacuo to remove the methanol, and the residue extracted with
ethyl acetate. There was obtained product weighing 3.6 g.
and having a melting point of about 133-136C. aEter recr~s-
tallization from a mixture of benzene and hexane. The
product was identified by NMR spectrum and elemental
analyses as 2-amino-6-trifluoromethylpyrazine.
Analyses calcd. for C5H4F3N3:
Theoretical Found
C 36.82~ 37.11%
H 2.47 2.17
N 25.76 25.52
Preparation 30
2-Amino-5-trifluoromethylpyrazine
A solution of 18 g. of 4,5-diamino-6-hydroxy-
pyrimidine sulfate (commercially available) in 18Q ml. of
aqueous 3N sodium hydroxide was prepared and cooled, and to
the cooled mixture there was added 25.2 g. of 3,3-dibromo-
l,l,l-trifluoropropanone. The reaction mixture was stirred
for about 48 hours at room temperature. The precipitate
which formed was ~iltered off, dissolved in 140 ml. of
aqueous 60% sulfuric acid, and heated at about 135C. for
about 8 hours. The reaction mix~ure was poured over crushed
ica and the aqueous mixture neutralized using concentrated
aqueous ammonium hydroxide. The solution was then extracted
with ethyl acetate. The ethyl acetate extracts were concen-
trated in vacuo to dryness and the residue recrystallized
from a mixture of benzene and hexane to yield product
weighing 2.2 g., and having a melting point of about 118-122C.
The product was identified by NMR spectrum and elemental
analyses as 2-amino-5-trifluoromethylpyra2ine.
X-5~51 -24-
~12~36~
Analyses calcd. Eor C5H4F3N3:
Theoretical Found
C 36.82% 37.04%
H 2.47 2.58
N 25.76 25.97
Preparation _
2-Amino-5-phenyl-6-trifluoromethylpyrazine
This intermediate was prepared stepwise.
Following the procedure of Lombardino, J. Het.
Chem., 10, 697 (1973), there was prepared 1-phenyl-3,3,3-
trifluoro-1,2-propanedione monohydrate.
To a sol~tion of 1.8 g. of 1-phenyl-3,3,3-tri-
fluoro-1,2-propanedione monohydrate in 40 ml. of methanol,
cooled in an ice bath, there was added, with stirring, 2 g.
of aminoacetamidine dihydrobromide. Stirring was continued
while 8.6 ml. of aqueous 2N sodium hydroxide was added. The
reaction mixture was then stirred at room temperature for
about two hours, and then stirred and refluxed for about
four hours. The reaction mixture was cooled and acidified
with dilute aqueous hydrochloric acid~ Water was added, and
the mixture extracted with 100 ml. of ethyl acetate. The
ethyl acetate extract was dried over anhydrous magnesium
sulfate, the drying agent filtered off, and the filtrate
concentrated ln vacuo. The residue thus obtained was
dissolved in chloroform, and chromatographed on a silica gel
column using chloroform as the eluant. There was obtained
material weighing 100 mg., and identified as 2-amino-5-
phenyl-6-trifluoromethylpyrazin~.
X-50501 -25-
Preparatlon _
2-Amino-5-(4-bromophe~)-6-chloropyrazine
This compound was prepared stepwiseO
Step 1. A mixture of 37 g. of 1-(4-bromophen~
1,2-propanedione-2-oxime, 3~ g~ of the tosylate salt of
ethyl aminocyanoacetate, and 750 ml. isopropanol was stirred
at room temperature for about 6 days. Another 12 gO of the
above-identified tosylate salt was added to the reaction
mixture and stirring at room temperature continued for 24
hours. Another 3 g. of the tosylate salt was added to the
reaction mixture and stirring continued at room temperature
for several more da~s. The reaction mixture was cooled, and
the solid which precipitated was filtered off. The solid
was extracted with 2 liters of boiling ethyl acetate, and
the solid filtered off. The filtrate was concentrated in
vacuo to about 900 ml. The solution was filtered again and
then cooled. The crystalline material which separated was
filtered off. It had a melting point of about 200-205C.,
and was identified by NMR spectrum as 2-amino-5-(4-bromo-
phenyl)-3-carbethoxypyrazine-1-oxîde. ~ield: 11 g.
Step 2. A mixture of 60 ml. of phosphorus oxy-
chloride, 10 ml. dimethylformamide was stirred and 12.1 g.
of 2-amino-5-(4-bromophenyl)-3-carbethoxypyrazine-1-oxide
~prepared as above) added in small amounts. When the
addition was complete, the reaction mixture was stirred at
reflux for about 15 minutes, after which the excess phos-
phorus oxychloride was removed in vacuoO Ice was added very
carefully to the residue, and the mixture made basic by
adding solid sodium bicarbonate. The mixture was extracted
X-5051 -26-
6~
with 800 ml. of chloroform and the chloroform extract dried
over anhydrous magnesium sulfate. The drying agent was
filtered off and the filtrate concentrated to dryness ln
vacuo to leave a black solid. The black solid was extracted
with 4 x 500 ml. portions of boiling cyclohexane. The
combined cyclohexane extracts were combined and concentrated
to a volume of about 300 ml. A beige solid separated which
had a melting point of about 151-153C., and which was
identified by NMR spectrum as 5-(4-bromophenyl)-3-carbethoxy-
6-chloro-2-{[(dimethylamino)methylene]imino}pyrazine.
Yield: 10.5 g.
Step 3. ,A mixture of 12 g. of 5-(4-bromophenyl)-
3-carbethoxy-6-chloro-2-{[(dimethylamino)methylene]imino3-
pyrazine (prepared as in Step 2, above) and 150 ml. of
a~ueous 2N hydrochloric acid was stirred and refluxed for
about 5 minutes, during which time a white precipitate
formed. The mixture was cooled and about 50 ml. of aqueous
lN sodium hydroxide solution was added. The mixture was
filtered and the solid which was collected on the filter was
washed with water. A sample of the solid recrystallized
from ethanol had a melting point of about 207-208C., and
was identified by NMR spectrum and elemental analyses as
2~amino-5-(4-bromophenyl)-3-carbethoxy-5-chloropyrazine.
Yield: 10 g.
Analyses calculated for C13HllBrClN3O2:
Theoretical Found
C 43.79 43.90
H 3.11 3.33
N 11.78 11.59
X-5051 -27-
-
.Z9~36~
Step 4. A mixture of 10 9. of the 2-amino-
5-(4-bromophenyl)-3-carbethoxy-6-chloropyrazine, 15 ml. of
dioxane, 75 ml. of water, and 8 y. of sodium hydroxide
pellets was heated briefly to reEluxing, at which time
complete solution was obtained. The mixture was acidified
with acetic acid and cooled. The solid which separated was
filtered off and slurried with aqueous lN hydrochloric acid.
The mixture was filtered to collect the solid product.
sample recrystallized from ethanol had melting point of
about 212-214GC., and was identified by NMR spectrum and
elemental analyses at 2-amino-5-(4-bromophenyl)-3-carboxy-
6-chloropyrazine. ,Yield: 9 g.
Analyses calculated for CllH7BrClN3O2o
Theoretical Found
C ~0.21 ~0.10
H 2.15 2.23
N 12.79 12.63
Step 5. A mixture of 9 g. of 2-amino-5-~4-
bromophenyl)-3-carboxy-6-chloropyrazine and 50 ml. of
tetralin was refluxed for about 15 minutes. The mixture was
cooled and 75 ml. of hexane was added. The solid which
separated was filtered off and washed with hexane. The
solid was recrystallized from ethyl acetate to yield product
having a melting point of about 254~256C. and identified by
NMR spectrum as 2-amino-5-~4-bromophenyl)-6-chloropyrazine.
Yield 4 g.
The syntheses of the novel compounds of formula I
are exemplified by the following examples, but the scope of
the invention is not to be considered as limited thereby.
X-5051 -2~-
~29~
Example ~
1-(2-Chlorobenzoyl)-3-[5-(4-bromophenyl)-6-methyl-2-
pyrazlnyl]urea
To a mixture of 2.6 g. oE 2-amino-5~(4-bromo-
phenyl)-6-methylpyrazine in 100 ml. of e-thyl acetate was
added 2.0 g. of 2-chlorobenzoyl isocyana-te and the mixture
stirred overnight a-t room temperature. The mixtura was
filtered. The solid material which was collected upon the
filter was recrystallized from ethanol to yield product
having a melting point of about 230-232C. The product was
identified by elemental analyses and NMR and infrared
spectra as l-(2-ch~orobenzoyl)-3-[5-(4-bromophenyl)-6-
methyl-2-pyrazinyl]urea.
Analyses calcd. for ClgH18BrClN4o2:
Theoretical Found
C 51.20% 51.03%
H 3.17 3.37
N 12.57 12.62
F'ollowing the general procedure of Example 1, and
using appropriate starting materials, the ~ollowing additional
compounds were prepared and identified by elemental analyses,
NMR, and infrared spectra.
lA. 1-(2-Chlorobenzoyl)-3-(5-trifluoromethyl-
2-pyrazinyl)urea, having a melting point of about 219-220C.
from 500 mg. of 2-amino-5-trifluoromethylpyrazine and
600 mg. of 2-chlorobenzoyl isocyana-te.
lB. 1-(2-Chlorobenzoyl)-3-(5-phenyl-2 pyrazinyl)-
urea, having a melting point of about 222-224C., from
1.0 g. of 2-amino-5-phenylpyrazine and 1.0 g. of 2-chloro-
benzoyl isocyanate.
X-5051 -29-
lC. 1-(2-Bromobenzoyl)-3-[5-(4-bromophenyl)-
6-methyl-2-pyrazinyl]urea, haviny a melting point of about
220-222C., from 2.0 g. of 2-amino-5-(4-bromophenyl)-
6-methylpyrazine and 2.0 g. of 2-bromobenzoyl i~ocyanate.
lD. 1-[5-(4-Bromophenyl)-6~methyl-2-pyrazinyl]-
3-(2-methylbenzoyl)urea, having a melting point of about
247-248C., from 1.0 g. of 2-amino-5-(4-bromophenyl)-
6-methylpyrazine and 1.0 g. of 2-methylbenzoyl isocyanate.
lE. 1-(2-Chlorobenzoyl)-3-[5-(4 ethylphenyl)-
6-methyl-2-pyrazinyl]urea, having a melting point of about
212-214C., from 500 mg. of 2-amino-5-(4-ethylphenyl)-6-
methylpyrazine and,excess 2-chlorobenzoyl isocyanate.
lF. 1-(2-Chlorobenzoyl)-3-(6-chloro-2-pyrazinyl)-
urea, having a melting point of about 202-203C., from
1.5 g. of 2-amino-6-chloropyrazine and 2.0 g. of 2-chloro-
benzoyl isocyanate.
lG. 1-(2-Chlorobenzoyl)-3-(6-trifluoxomethyl-2-
pyrazinyl)urea, having a melting point of about 179-180C.I
from 1.5 g. of 2-amino-6-trifluoromethylpyrazine and 1.6 g.
0 of 2-chlorobenzoyl isocyanate.
lH. 1-(2-Chlorobenzoyl)-3-[5-(4-methylphenyl)-
2-pyrazinyl]urea, having a melting point of about 230-232C.,
frcm 600 mg. of 2-amino-5-(4-methylphenyl)pyrazine and
600 mg. of 2-chlorobenzoyl isocyanate.
lI. 1-(2-Chlorobenzoyl)-3-[5-(4-chlorophenyl)-
6-methyl-2-pyrazinyl]urea, having a melting point of about
228-229C., from 600 mg. of 2~amino-5-(4-chlorophenyl)-
6-methylpyrazine and 1.0 g. of 2-chlorobenzoyl isocyanate.
X-5051 -30-
136i
lJ. 1-(2-Chlorobenzoyl)-3-(6-methyl-5-phenyl-
2-pyrazinyl)urea, having a meltiny point of about 221-222C.,
from 500 mg. of 2-amino-6-methyl-5-phenylpyrazine and excess
2-chlorobenzoyl isocyanate.
lK. l-(2-sromobenzoyl)-3-t5-trifluorometh
2-pyrazinyl)urea, having a melting point of about 206-208C.,
from 300 mg. of 2-amino-5-trifluoromethylpyrazine and
500 mg. of 2-bromobenzoyl isocyanate.
lL. 1-(2-Chlorobenzoyl)-3-[5-(4-bromophenyl)-
6-chloro-2-pyrazinyl]urea, weighing 1.4 g., and having a
melting point of about 240-242C., from 0.9 g. of 2-amino-
5-~4-bromophenyl)-~-chloropyrazine and 0.65 g. of 2-chloro-
benzoyl isccyanate.
Example _
1-(2-Chlorobenzoyl)-3-[5-(4-chlorophenyl)-2-pyrazinyl]urea
To a solution of 0.5 g. of 2-amino-5-(4-chloro-
phenyl)pyrazine in 30 ml. of dimethylformamide there was
added 0.95 g. of 2-chlorobenzoyl isocyanate, and the mixture
was stirred at ambient room temperature for about 3-4
hours. At the end of that time the solution was poured on
¢rushed ice and the precipitate which formed was collected
and washed with water. The crude material, which weighed
950 mg., was recrystallized twice from a mixture of ethyl
acetate and a small amount of dimethylformamide to yield
product weighing 200 mg., and having a melting point of
about 231-234C. This product was identified by elemental
analyses and NMR spectrum as l-(2-chlorobenzoyl)-3-~5-(4-
chlorophenyl)-2-pyrazinyl]urea.
X-5051 -31-
- ~L2~6~
Analyses calculated for C18H16C12N4O2
Theoretical Found
C 55.82 56.0~
H 3.12 3.07
N 14.47 14.58
Following the general procedure o~ Example 2, and
using appropriate starting materials, the following additional
compounds were prepared and identified by elemental analyses
and NMR spectra.
2A. 1-(2-Chlorobenzoyl)-3-[6-methyl-5~(a,a,a-
trifluoro-_~tolyl)-2-pyrazinyl]urea, having a melting point
of about 202-204~., and weighing 0.95 g., was obtained from
1.0 g. of 2-amino-5-(a,a,a-trifluoro-m-toIyl)-6-methyl-
pyrazine and 1.3 g. of 2-chlorobenzoyl isocyanate.
2B. 1-(2-Chlorobenzoyl)-3-[5-(4-methoxyphenyl)-
6-methyl-2-pyrazinyl]urea, having a melting point of about
218-221C., and weighing 0.5 g., from 0.6 g. of 2-amino-
5-(4-methoxyphenyl)-6-methylpyrazine and 0.95 g. of 2-
chlorobenzoyl isocyanate.
2C. 1-(2-Chlorobenzoyl)-3-[5-(2,4-xylyl)-2-
pyrazinyllurea, having a melting point of about 218-220C.,
and weighing 1.06 g., from 0.77 g. of 2-amino-5-(2,4~
xylyl)pyrazine and 1.2 g. of 2-chlorobenzoyl isocyanate.
2D. 1-(2-Methylbenzoyl)-3-[6-methyl-5-(a,a,a-
trifluoro-_-tolyl)-2-pyrazinyl~urea/ having a melting point
of about 211-212C., and weighing 230 mg., was obtained from
0.5 g. of 2-amino-5-(a,a,a-trifluoro-m-tolyl)-6-methyl-
pyrazine and 0.75 g. of 2-methylbenzoyl isocyanate.
X-5051 -32-
~L~2~
2E. 1-[5-~4-Methoxyphenyl)-6-methyl-2-pyrazinyl]-
3-(2-methylbenzoyl)urea, having a melting point of about
235-238C., and weighing 400 mg., from 0.6 ~. of 2-amino-
5-(4-methoxyphenyl)-6-methylpyrazine and 1.0 g. of 2-
methylbenzoyl isocyanate.
2F. 1-(2-Chlorobenzoyl)-3 [6-methyl-5-~4-methyl-
phenyl)-2-pyrazinyl]urea, having a melting point of about
216-217C., and weighing 0.7 g., from 0.6 g. o 2-amino-
6-methyl-5-(4-methylphenyl)pyrazine and 0.8 g~ of 2-
chlorobenzoyl isocyanate.
2G. 1-[5-(4-Bromophenyl)-2-pyrazinyl}-3-(2-
chlorobenzoyl)urea~ having a melting point of about 227-
231C., and weighing 0.7 g., from 0.7 g. of 2-amino-
5-(4-bromophenyl)pyrazine and 1.0 g. of 2-chlorobenzoyl
isocyanate.
2H. 1-[5-(4-Bromophenyl)-6-ethyl-2-pyrazinyl~-
3-(2-chlorobenzoyl)urea, having a melting point of about
208-210C., and weighing 270 mg., from 0.6 g. of 2-amino-
5-(4-bromophenyl)-6-ethylpyrazine and 1.0 g. of 2-chloro-
benzoyl isocyanate.
2I. 1-(2-Chlorobenzoyl)-3-[6-methyl-5-(4-phenoxy-
phenyl)-2-pyrazinyl]urea, having a melting point of about
204-207C., and weighing 370 mg., from 0.5 g. of 2-amino-
6-methyl-5-(4-phenoxyphenyl)pyrazine and 0.8 g. af 2
chlorobenzoyl isocyanate.
2J. 1-(2-Chlorobenzoyl)-3-~6-methyl-5-(4-biphenyl~
yl)-2-pyraæinyl]urea, having a m~lting point of about
234-237C., and weighing 0.58 g., from 0.85 g. of 2-
amino-6-methyl-5-~4-blphenylyl)pyrazine and 0.7 g. of
2-chlorobenzoyl isocyanate.
X-5051 _33_
9~
2K. 1-(2-Chlorobenzoyl)-3-[5-(4-fluorophenyl)-6-
methyl-2-pyrazinyl]urea, having a mel-ting point of about
211-212C., and weighing 0.7 g., from 0.6 g. o 2-amino-
5-(4-fluorophenyl)-6-methylpyra2ine and 0.6 g. of 2-
chlorobenzoyl isocyanate.
2L. 1-(2-Chlorobenzoyl)-3-[5-(4-fluorophenyl)-2-
pyrazinyl]urea, weighing 0.2 g., and having a melting point
of about 230-234C., from 0.5 g. of 2-amino-5-(4-fluoro-
phenyl)pyrazine and 0.5 g. of 2-chlorobenzoyl isocyanate.
2M. 1-(2-Chlorobenzoyl)-3-E5-(a,a,a-tri~luoro-_-
tolyl)-2-pyrazinyl~urea, having a melting point of about
213-215C., and we~ghing 0.6 g., from 0.6 g. of 2-amino-S-
(a,a~a-trifluoro-p-tolyl)pyra7ine and 0.55 g. of 2-chloro-
benzoyl isocyanate.
Example _
1-[5-(3-Bromophenyl)-6-methyl-2 pyrazinyl~-3-(2-chloro-
benzoyl)urea
A suspension of 0.7 g. of 2-amino-5-(3-bromo-
phenyl~-6-methylpyrazine in 10 ml. of dichloroethane under
dry nitrogen was prepared and there was added thereto with
stirring 0.52 g. of 2-chlorobenzoyl isocyanate. A solid
precipitate formed immediately. After stirring the mixture
for about 30 minutes, the solid was filtered off and re-
crystallized from a mixture of commercial absolute ethanol
and dimethylformamide. There was obtained product having a
melting point of about 201-203C., and weighing 370 mg. It
was identified by NMR spectrum and elemental analyses as
1-[5-(3-bromophenyl)~5-methyl-2-pyrazinyl]-3~(2-chloro
benzoyl)urea.
X-5051 _34_
~'lf~9f~6~
Analyses calculated for ClgH15BrClN~O2:
Theoretical Found
C 51.20 51.24
}I 3.17 3.~4
N 12.57 12.77
Fvllowing the same general procedure as in Example
3, and using appropriate starting materials, the following
additional compounds were prepared and identified by elemental
analyses and NMR spectrum.
3A. 1-(2-Chlorobenzoyl)-3-(5-cyclohexyl-6-
methyl-2-pyrazinyl)urea, having a melting point of about
203-205C., and welghing 1.0 g., from 0.6 g. of 2-amino-
5-cyclohexyl-6-methylpyrazine and 0O63 g. of 2-chlorobenzoyl
isocyanate.
3B. 1-(2-Chlorobenzoyl)-3-[5-(4-methylthiophenyl)-
6-methyl-2-pyrazinyl]urea, having a melting point of about
215-216C., and weighing 0.7 g., from 0~7 g. of 2-amino-
5-(4-methylthiophenyl) 6-methylpyrazine and 0.6 g. of
2-chlorobenzoyl isocyanate.
3C. 1-(2 Chlorobenzoyl)-3-[6-methyl-5-(2-tolyl)-
2-pyrazinyl~urea, weighing 0.22 g., and having a melting
point of about 206-207C., from 0.35 g. of 2-amino-6-
methyl-5-(2-tolyl)pyrazine and 0.4 g. of 2-chlorobenzoyl
isocyanate.
The compounds of formula I are useful for the
control of insects of various orders, including Coleoptera
such as Mexican bean beetle, boll weevil, corn rootworm,
cereal leaf beetle, flea beetles, borers, Colorado potato
beetle, grain beetlest alfalfa weevil, carpet beetle,
X-5051 -35-
'
~12~86~
confused flour beetle/ powder post beetle, wireworms, riceweevil, rose beetle, plum curculio, white grubs; Diptera,
such as house fly, yellow fever mosquito, stable fly, horn
fly, blowfly, cabbage maggot, carrot rust fly; Lepidopt0ra,
such as Southern armyworm, 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 army-
worm; and Orthoptera, such as German cockroach and American
- 10 cockroach.
It has been found that the novel compounds of
formula I interfere with the mechanism of metamorphosis
which occurs in insects, causing the death of the insects.
It has also been found that compounds of formula I
wherein
A is bromo or chloro;
R~` is hydrogen, trifluoromethyl, or
-(CH ) -~
R2 is hydrogen, chloro, methyl, or trifluoro-
methyl;
R3 is hydrogen, halo, methoxy, trifluoromethyl, or
phenyl;
m is 0 or 1; and
n is 0,
have ovicidal activity.
The novel compounds of formula I are therefore ;
useful in a method for the control of insects of an order
selected from the group consisting of Coleoptera, Diptera,
X-5051 -36-
1~986~
Lepidoptera, and Orthoptera, which comprises applying to the
loci of the insects an insecticidally-effective amount of a
l-(mono-o-substituted benzoyl)-3-(substituted p~razinyl)urea
of formula I.
The insecticidal method is practiced by applying
to the loci of the insects an insecticidal compos~tion which
comprises an insecticidally-effective amount of a compound
of formula I and a solid or liquid carrier,
The novel compounds of formula I are formulated
for use as insecticides by being mixed with a solid carrier
material or dissolved or dispersed in a liquid carrier
material. Include,d in such mixtures, if desired, are
adjuvan~s such as surface-active substances and stabilizers.
These formulations can include aqueous solutions
and dispersions, oil solutions and oil dispersions, pastes,
dusts, wettable powders, miscible oils, granules, aerosol
preparations and the like.
The wettable powders, pastes and miscible oils are
formulations in concentrated form which are diluted with
water before or during use.
The granular preparations are produced by taking
up the novel compound in a solvent, after which granular
carrier material such as porous granules, for example,
pumice or attapulgite clay; mineral non-porous granules,
such as sand or ground marl; or organic granules are im-
pregnated with the solution, suitably in the presence of a
binder. Such preparations contain from about 1 to about 15
percent active ingredient, suitably about 5 percent.
X-5051 -37-
6~L
Dust formulations are prepared bv intimately
mixing the active compound with an inert solid carrier
material in a concentration of, for example, from about 1 to
about 50 percent by weight. Examples of suitable solid
carrier materials include talc, kaolin, diatomaceous earth,
dolomite, gypsum, chalk, bentonite, and attapulgite, or
mixtures of these and similar substances. It is also
possible to use organic carrier materials such as ground
walnut shells.
Wettable powder formulations are produced by
mixing from about 10 to about 80 parts by weight of a solid
inert carrier, suc~ as one of the aforementioned carrier
materials, with from about 10 to about 80 parts by weight of
the active compound, together with from about 1 to about 5
parts by weight of a dispersing agent, such as for example,
the ligninsulfonates or alkylnaphthalenesulfonates, and
preferably also with from about 0.5 to about 5 parts by
weight of a wetting agent, such as one of the fatty alcohol
sulfates, alkylarylsulfonates, or fatty acid condensation
products.
Miscible oil formulations are prepared by dis-
solving the active compound in or suspending the active
compound in a suitable solvent which is preferably rather
immiscible with water, after which an emulsifier is added to
the preparation. Suitable solvents include xylene, toluene,
and high aromatic petroleum distillates, for example solvent
naphtha, distilled tar oil, and mixtures of these. Suitable
emulsifiers include alkvlphenoxypolyglycol ethers, polyoxy-
ethylene sorbitan esters of fatty acids, or polyoxyethylene
X-5051 -38-
-
~Z~8~
sorbitol esters of fatty acids. These miscible oils contain
the active compound in a concentration of from about 2
percent to about 50 percent by weight.
When an aerosol preparation is desired, such
aerosol preparation can be obtained in the usual manner by
incorporating the active compound in a solvent in a volatile
liquid suitable for use as a propellank, for example, one of
the commercially available fluorocarbon propellants.
As is ~ell understood, the preparations containing
one of ~he active compounds of formula I may also include
other known pesticidal compounds. This of course broadens
the spectrum of ac,tivity of the preparation.
The amount of 1 (mono-o-substituted benzoyl)-
3-(substituted pyrazinyl)urea to be applied for insect
control purposes to a given area of plant life is, of
course, dependent upon a variety of factors, such as the
extent of vegetative surface to be covered, the s`everity of
the insect infestation, the condition of the foliage treated,
the temperature, and the humidity. In general, however, the
application of the active ingredient in a formulation
containing a concentration of the active ingredient of from
about 0.1 to about 1000 ppm. is desirable.
The insecticidal activity of the novel compounds
of formula I has been determined by testing the efficacy of
formulations of the compounds against Mexican bean beetle
larvae (Epilachna varivestia), and against Southern arm~worm
larvae (Spodoptera eridania) in an insecticide screen.
These insects are members of the Coleoptera and Lepidoptera
orders of insects, respectively. The compounds have been
X-5051 -39-
~lZ9~i~
, ) -
tested in several tests against these insects at rates o~
fxom about 1000 ppm. down to about 1 ppm., the compounds
being applied at these rates to leaves of plants upon which
the above-identi~ied larvae feed.
Experiment _
The following procedure was used to evalua~e the
efficacy of -the novel compounds of formula I as insecticides.
Bean plants were grown in four-inch square pots,
with there being 6 to 10 plants per pot. When the plants
~ere 10 days old, they were ready for use in this exper-
iment.
Each teSt compound was formulated by dissolving 10
mg. of the test compound in 1 ml. of solvent (23 g. Toximul
R plus 13 g. Toximul~S per liter of 1:1 anhydrous ethanol
and acetone) followed by mixing with 9 ml. of water to give
a 1000 parts per million (ppm.) concentration of the test
compound in the solution. (Toximul R and Toximul S are each
a sulfonate/nonionic blend produced by Stepan Chemical
Company, Northfield, ILlinois.~ A portion of the 1000 ppm.
concentration of test solution of each compound was then
diluted in the ratio of 1:10 with the stated solvent to
provide a test solution having a concentration of 100 ppm.
The solution of test compound, at each concentration, was
then sprayed onto the bean plants in each 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
X-5051 ~40-
P~
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8~i~
armyworm larvae (Spodoptera eridania) were placed in each of
three dishes. The dishes were the~ placed in a room wherein
the temperature and relative humidity were controlled at
about 25.5C. and a~out 51 percent, respectively, ~or a
period of about four days, at which time the first evalu-
ation of the eEfects of the test compounds was made. After
this evaluation, two fresh leaves from the original treated
pots were placed in each dish. The dishes were a~ain
maintained in the temperature and humidity controlled room
for an additional three days until the final seven da~
evaluation was made.
The perc~nt control was determined by counting the
number of living larvae per dish. All the treatments were
compared to sol~ent controls and nontreat~d controls. The
rating code (percent of control) used was as follows:
O = 0%
1 = 1-50%
2 = 51-99%
3 = 100~ control
The results of this test are set forth in Table 1,
which follows. In the table, column 1 identifies the com~
pounds by the number of the preparative example; column 2,
the application rate in parts per million (ppm.); and
columns 3 through 6 give the Rating Code at days 4 and 7 for
the two insects against which the compounds were tested at
the application rates of 1000 ppm. and 100 ppm.
X-5051 -~1-
~129869~
Table 1
~ =
Appln Mexican Bean Sou~hern
Rate Beetle Arm~worm
Compoun ~ Day 4 Day 7 Day 4 Day 7
11000 1 3 3 3
100 1 2 3 3
lA1000 1 2 2 2
100
lB1000 0 0 1 2
100 0 0 0
lC1000 0 3 3 3 ,t
100 0 2 3 3
lD1000 0 1 3 3
100 0 0 3 3
lE1000 0 2 3 3
100 0 3 3 3
lF1000 1 2 2 2
100 0 1 0 0
lG1000 0 3 2 2
100 0 2 0 0
lH1000 0 0 1 0
100 0 0 0 0
lI1000 0 2 3 3
100 0 1 3 3
IJ1000 0 1 3 3
100 0 0 2 2
lK1000 2 2 2 2
100 2 2 2 2
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~z~
Ta_le 1 (continued)
Rating Code
Appln Mexican Bean Southexn
Rate Beetle A~y~
Compound ~e~ ~ Day 7 Day 4 Day 7
lL1000 0 2 3 3
100 0 0 3 3
21000 0 0 3 3
100 0 3 3
2B1000 2 3 2 3
100 1 2 2 3
2C1000 0 0
100 0 0 0 0
2D1000 1 2 3 3
100 0 1 3 3
2E1000 0 1 3 3
100 0 0 2 3
2F1000 2 3 2 3
100 2 3 2 2
2~1000 0 0 3 3
100 0 0 2 3
2H1000 0 0 2 3
100 0 0 0
2I1000 2 2 2 2
100 1 2
2J1000 0 1 3 3
100 0 0 0
X-5051 -43-
~L12~86~
Table 1 ( continued )
Rating Code
Appln Mexican Bean Southern
Rate Beetle Armyworm
Compound ppm. Day 4 Day 7 Day 4 Day 7
31000 0 3 3 3
~00 0 1 2 2
3A1000 1 3 3 3
100 0 2 3 3
3B1000 1 3 2 3
100 0 1 0 2
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:
~9~;~
Ex~eriment 2
Several of the novel compounds tested in Exper-
iment 1, above, were retested, this time at lower levels o~
application. The preparation of the bean plants was the
same. The test compounds were formulated in the manner
described hereinbelow:
Ten mg. of test compound was dissolved in 1 ml. of
solvent and mixed with 9 ml. of water to give a 1000 ppm.
solution.
This solution was then serially diluted to obtain
the necessary concentrations of solution for conducting the
tests.
The solvent used was 50:50 alcohol:acetone plus 23
g. of Toximul R and 13 g. of Toximul S per liter.
The percent control was determined by counting the
number of living larvae of Southern armyworm (Spodoptera
eridania) 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 =
No. of survivors in control -No. of survivors in
treatment x 100
No. survlvors in control
The results are set forth in Table 2, which
follows. Where more than one replicate was run the recorded
results are averages.
X-5051 -45-
~l~Z98~1
Table 2
Percent Control
Southern
Appln. Armyworm
Rate
Compound ~. Day 4 Day
100 100 100
100 100
100 100
9S 100
57 96
2.5 54 93
1.0 17 76
~0.5 0 20
lC 100 100 100
100 10~
100 100
100 100
100 100
2.5 100 100
1.0 60 93
0~5 20 73
lD 100 100 100
100 100
100 100
100 100
100 100
2.5 100 100
1.0 33 67
0.5 7 27
X-5051 -46-
Table 2 (contlnued)
Percent Control
Southern
Appln. Army~rm
Rate
Compound ppm. Day 4 Day 7
lE 100 100 100
100 100
100 100
81 93
100
2, 5 27 47
lI 100 100 100
100 100
100 100
100 100
96 100
2. 5 80 100
1. 0 20 73
0.5 0 53
lL 10 100 100
13 75
2 100 1()0 100
93 100
93 100
lû 57 100
76
~. 5 13 ~7
1.0 0
- ` 0.~ 7 7
X- 5 0 51 - 4 7-
~Z~86~
Table 2 (continued)
Percent Control
3c~
Appln. Armyworm
Rate
Compoundppm. Day 4 Day_7
2A 100 100 100
100 100
100 100
100 100
10~ 100
2.5 93 100
1.0 20 80
0.5 23 40
2B 100 93 100
100 100
86 93
27 73
2D 100 100 100
100 100
100 100
100 100
100 100
2.5 100 100
1.0 53 100
2E 100 100 100
100 100
100 100
8~ 1~0
27 73
X-5~51 -4~-
~z~
Table 2 tcontinued)
Percent Control
Southern
Appln. Armyworm
Rate
Compoundppm. Da~ 4 Day 7
2.5 27 47
1.0 20 27
2F 100 100 100
87 93
93 100
67 93
2G 100 100 100
93 100
100 100
100
2K 10 100 100
73
3~ 10 67 100
0 27
X-5051 -49-
~lZ98~
Experiment _
One of the compounds coming within the scope o
generic formula I, ~e~ was also tested against Egyptian
cotton leaf worm larvae (~odoE~tera li*toralis).
The test compound, technical material, was dis-
solved in acetone and the solution diluted with water con-
taining a surfactant.
Cauliflower plants were sprayed with the thus
Eormulated compound in the field. Leaves were collected and
fed in the laboratory to field-collected Egyptian cotton
leaf worm larvae, lst-3rd instars. Mortality at 4 days and
7 days feeding at rates from 100 ppm. downward was recorded,
and appears in Table 3, which follows. The test compound is
identified by the number of i`ts preparative example.
Table 3
Percent Mortality
2nd Instar Larvae
Appln. of Egyptian cotton
Rate leaf worm
Com~ound ppm. Day 4 Day 7
100 90 100
100
100
100
After the 7 day reading, additional cauliflower
leaves were collected in the field from selected treat-
ments, and the residual activity determined by 4 and 7
day observations made in the same way as described above.
The results are recorded in Table 4, which follows.
X-5051 -so
l2~
Table 4
Percent Mortality
2nd Instar Larvae
Appln. of Egyptian cotton
Rate leaf worm
Compound ppm. Day 4 Day 7
100 ~0 100
100
100
0 80
Experiment 4
This experiment was conducted to determine the
local systemic activity of several compounds of the instant
application.
The test compounds were each formulated as a
50 WP (50% wettable powder). Each formulation was diluted
with water to give the desired concentration of test material.
Soybean seeds (variety Calland) were planted and
allowed to germinate. Seven days after planting, when the
cotyledonary leaves had formed, the soybean plants were
sprayed to runoff with the test materials, and the plants
were returned to the greenhouse for one week. At the end
of the week, the plants were harvested and sectioned, and
the cotyledonary leaves (sprayed leaves) were separated
from the new growth, or the trifoliate leaves (new leaves),
which developed in the 7-day period after spraying.
The sprayed leaves were placed in a Petri dish
with second and third instar larvae of Southern armyworm
(Spodoptera eridania); and the new leaves were placed in
X-5~51 -51-
~.~2~
separate Petri dishes with second and third instar larvae
of Southern armyworm. The dishes were placed in a room
wherein the temperature and humidity were controlled at
about 25.5C. and about 51 percent, respectively~
After four days, the larvae were observed to
determine the effects of the test compounds. After this
evaluation, the surviving larvae from the treated and the
new leaves, respectively, were transferred to clean Petri
dishes containing untreated soybean leaves. The dishes
were again maintained in the temperature and humidity con-
trolled room for an additional three days until the final
seven day evaluatio,n was made.
The percent control was determined in the same
manner as described in Experiment 2, above, using the
same formula. The results are recorded in Table 5, which
follows.
In the tabler Column l identifies the test com-
pound by the number of its preparative example in the
Speci~ication; Column 2, identifies the rate of application
in parts per million (ppm.); Columns 3 and 4, the percent
control on sprayed and new foliage, respectively, on
Day 4; and Column 5~ and 6, the percent control on
sprayed and new foliage, respectively, on Day 7.
X-5051 -52-
Table 5
.
Perc_ Control
Appln.Southe n A_myworm
Rate ~a~ 4 ~ y_~
Compoundppm. Spra~ed New ~_ayed New
1 1000 100 78 100 100
100 100 22 100 9~
29 0 88 28
lC1000 100 94 100 9~
100 100 55 100 89
47 0 100 22
lD1000 100 78 100 100
100 100 17 100 83
' 10 23 0 88 22
These results show that translocation of the
insecticidal test compounds occurs in soybeans~
Experiment 5
Several of the novel compounds of formula I were
tested for their efficacy as insecticides against the yellow
fever mosquito, Aedes aegypti, of the order of Diptera.
Each test compound was formulated by dissolving
10 mg. of the compound in 1 ml. of acetone and mixing with
99 ml. of water to give a concentration of 100 ppm of the
compound in the test solution. ~he lower concentrations of
test solutions needed were then obtained by serial dilution
of the 100 ppm solution with water. These test solutions
were then placed in 100 ml. glass beakers, or, alternatively,
6 o~. plastic containers, 40 ml. of test solution per beaker
or container, and 2 beakers or containers per rate. Twenty
to thirty, 24-hour mosquito larvae were placed in each
beaker. The larvae were fed 10-20 mg. of pulverized Purina
X-5051 -53-
1~29~36~
laboratory chow daily for 7 days. During this time the
beakers or containers were maintained in a room in which the
temperature and humidity were continuously controlled and
recorded, as described in Experiment 1.
The percent mortalities of the mo~quito larvae
were determined after 7 days by visual observation of the
number of living larvae. All the treatments were compared
to solvent and nontreated controls. The results are set
forth in Table 5, which follows.
In the table, column 1 identifies the compounds by
the number of the preparative example; column 2, the appli-
cation rate in ppm~ and column 3, the percent mortality at
the indicated test rates.
Table 6
Yellow Fever Mosquito Larvacide Test
Compound Appln. Rate ppm. Percent Mortality
O. 01 100
lC 0.01 100
lI 0.01 100
Solvent -- 0
Untreated -- o
Experiment 6
This experiment was conducted to determine the
ovicidal activity of several compounds of the instant
application using egg clusters of Southern armyworm
(Spodoptera eridania) and Mexican bean beetle (Epilachna
varvestis3.
X-5051 -54-
~z~
The egg clusters, which were on Bountiful variety
bean leaves, were placed on a paper towel and sprayed at low
air pressure (approximately 0.21 x 106 dynes/cm.2) usiny a
DeVilbiss atomizer sprayer to apply the test formulations of
the compounds. These formulations were prepared in the same
manner as described in Experiment 1, supra. After the
spraying, the eggs were blotted with towel paper and placed
in plastic Petri dishes (60 x 15 ml.) alon~ with a piece of
moist dental wick. The egg clusters in the Petri dishes
were then incubated until the non-treated controls hatched.
At that time, observations were made to determine the number
of eggs which hatc~ed. The results were recorded as the
percent control. These results appear in Table 7, which
follows. In the table, Column 1 identifies the test compound;
Column 2, the application rate in parts per million; and
Column 3, the percent control achieved.
!
X-5051 _55_
~125~36~
Table_7
Appln. ~
Rate Percent K111
Compound pEn~. SAW MBB
1000 100
500 100
250 100
100 100
100
lC 1000 100
500 100
250 100
,L00 100
lF 1000 100
lG 1000 100
lI 1000 100
500 100
250 100
100 100
1~ lOOQ 100
lK 1000 100
500 100
250 100
100 100
100
2A 1000 100
500 100
250 100
100 100
100
X-5051 -56
986~
Table 7, cont'd
Appln.
Rate Percent Kill
Compound ppm. SAW MBB
2B 1000 100
50Q ~00
250 95
100 100
2J 1000 100
2K 1000 100 100
500 100 96
250 100 96
100 100
100
100
96
100
3 1000 100
The results of the tests show that the novel com-
pounds coming within the scope of formula I, supra, are
active against a number of insects in the larval stage, as
the insects ingest the leaves, or any other paxt o~ their
normal habitat, e.g., water, manure, and the like, to which
the active compounds have been applied. Also, novel com-
pounds coming within the scope of formula I, supra, are
shown to be active as ovicidal agents.
~-5Q51 -57-
