DE2826893A1 - METHOD FOR PRODUCING 1- (MONO-O-SUBSTITUTED-BENZOYL) -3- (SUBSTITUTED-PYRAZINYL) UREA - Google Patents

Description

PFENNING MAAS MElNIG - LEMKE - Mockery

6CHLEISSHEiMERSTR. 299

βΟΟΟ MUNICH 40

X-5051

Eli Lilly and Company, Indianapolis, Indiana, V.St.A.

Process for the production of

1- (mono-o-substituted- b enzo yl) -3- ( substituted-pyrazinyl)

ureas

The control of insects is ever increasing in today's world World population of vital importance. Insects, such as those belonging to the genera Lepidoptera, Coleoptera, Diptera, Homoptera, Hemiptera and Orthoptera are known to cause great damage in the larval state in crops, such as those used as food Crops and fibrous crops. Fighting such insects is important for the well-being of mankind, because this increases the yield of the nutritional crops and of the fibrous crops, for example can be used for the manufacture of clothing, increase.

A number of substituted benzoylureas are already disclosed in US Pat. No. 3,748,356 described, which are said to have a strong insecticidal effect. These compounds are generally 1- (2,6-dichlorobenzoyl) -3- (substituted-phenyl) ureas, with this

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but also several 1- (2,6-dichlorobenzoyl) -3- (substituted-pyridyl) ureas belong. A number of methods of making such compounds exist, but they succeed this does not apply to the steps of the present procedure.

From US Pat. No. 3,989,842 insecticidal compositions and methods for controlling insects in agriculture and horticulture emerge, with certain N- (2,6-dihalogenobenzoyl) -N ¹ - (substituted-phenyl) ureas and several N- - (2, 6 ~ dichloro * - benzoyl) -N ¹ - (substituted-pyridyl) ureas can be used.

US Pat. No. 3,933,908 describes other N- (2,6-dihalobenzoyl) -N ¹ - (substituted-phenyl) ureas which are also said to be insecticidal.

The insecticidal effectiveness of 1 ~ (2,6-dichlorobenzoyl) -3- (3,4-dichlorophenyl) urea is discussed in a number of references. In detail, refer to the natural sciences , 59: 312-313 (1972); ibid. 60: 431-432 (1973) and Pestic. May be. 4, 737-745 (1973).

In J. Med. Ent. 10, 452-455 (1973) and J. Econ. Ent. 67, 300-301 (1974) describes studies on the inhibition of the formation of Mosquitoes and house flies as well as the control of alfalfa beetles with 1- (4-chlorophenyl) -3- (2,6-difluorobenzoyl) urea reported.

US Pat. No. 3,992,553 discloses mono-o-chloro-substituted-benzoylureidodiphenyl ethers known to be outstandingly insecticidal against plant pests and also ectoparasiticides should represent in veterinary medicine. ■

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From BE-PS 833 288 insecticidally effective disubstituted benzoylpyrazinyl ureas are known. That in it for making however, the method described for these compounds is different from the present production method.

In BE-PS 838 286 i-benzoyl-3- (4-phenoxyphenyl) ureas described, which are insecticidally effective and only have a low level of toxicity to mammals and plants.

The invention is now directed to a new process for the preparation of benzoylureas, and those obtainable hereafter Compounds are insecticides.

A process has now been found for the preparation of benzoylureas, as described, for example, in US Pat. No. 3,748,356 and BE-PS 833 288, which consists in the fact that a benzamide, a C 1 -C 4 -alkyllithium, a phenyl chloroformate is found and reacts an amine with one another. One embodiment of this process is that by treating the benzamide with the alkyllithium and a phenyl chloroformate in an inert solvent at about -80 to -40 ⁰ C, the urethane thus obtained as intermediate product is then reacted with an amine in an inert solvent at about -80 Treated to -40 ⁰ C and then slowly increased the temperature to about 50 to 100 ^{0 C to form the desired benzoylurea.} A second embodiment of the present process is that by treating the benzamide with an alkyl lithium in an inert solvent at about -80 to -40 ⁰ C, the lithium salt thus obtained then with a carbamate at a temperature of about -80 to -40 ⁰ C and the mixture can finally come to about 20 to 40 ⁰ C to form the desired benzoylurea. The carbamate required for this is formed by reacting an amine with a phenyl chloroformate.

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The process according to the invention for the preparation of 1- (monoo-substituted-benzoyl) -3- (substituted-pyrazinyl) ureas of formula I.

/ OH OH

J * V Il I Ί I .ζ V_ _C _ _h _-c — Ν — R (D

A chlorine, fluorine, bromine, methyl or trifluoromethyl

means,

B hydrogen, chlorine, fluorine, bromine, methyl or tri

is fluoromethyl,

R for

r Y

, y

"X / V ■

or

Αν ^r

stands, 809883/0713

R hydrogen, halogen, C.-C, -alkyl, halogen (C.-C.-

alkyl), cyano,

• 'f.

/ ""'S" ^Z -N

(CU) -

means,

R is hydrogen, halogen, methyl, ethyl, cyano or

Is halo (C ₁ -C ₄ ) alkyl,

R and R are identical or different and are hydrogen,

Halogen, Cj-Cg-alkyl, cyano or halo (C.-C.) alkyl mean,

R for halogen, halogen (C.-C.) alkyl, Cj-Cg-alkyl,

Is cyano or phenyl,

X denotes halogen or C ₁ -C.-alkyl,

Y is halogen,

Z represents oxygen or sulfur,

η stands for 0, 1 or 2,

ρ stands for 0 or 1 and

m stands for 0, 1, 2 or 3,

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is characterized in that one between the residues

/ ο

'I and

where A, B and R have the meanings given above, build a ureido bridge by either

(a) a benzamide of the formula

with a C.-C ₇ -alkyllithium and a phenyl chloroformate in an inert solvent at about -80 to -40 ⁰ C to form a urethane as an intermediate, this intermediate with an amine of the formula

is reacted in an inert solvent at about -80 to -40 ⁰ C and the reaction mixture is then slowly warmed and heated to about 50 to 100 ⁰ C to form the desired benzoylurea, or

(b) a benzamide of the formula

O if -C-MH

with a C.-C_-Alkyllithium in an inert solvent at about -80 to -40 ⁰ C with formation of the corresponding

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Reacts lithium salt and this lithium salt is then reacted with a carbamate of an amine of the formula RNH "and a phenyl chloroformate, this treatment being carried out in an inert solvent at about -80 to -4O ⁰ C with a subsequent slow increase in the temperature to about 20 to 40 ⁰ C carries out to form the desired benzoylurea.

Preferred compounds which can be prepared by the process according to the invention are those in which B has a different meaning has as hydrogen. Compounds in which A and B are chlorine are very particularly preferred.

In the above description, the individual terms have the meanings customary in chemistry. The alkyl groups can be straight or branched chain. Halogen is understood to mean fluorine, chlorine, bromine or iodine.

According to step (a) of the present process, compounds of the formula I are prepared according to the following reaction scheme:

S /

^Ί V ₁ ./OO. RNH ₂

S ι

0

¹¹ / \

For the above reaction, the benzamide used in stage 1 and the amine used in stage 2 are selected so that the desired one is obtained Benzoylurea yields. Benzamides are preferred in which

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A and B denote chlorine, fluorine or bromine, with dichlorobenzamide being particularly preferred. The preferred amine is a pyrazinylamine, a benzopyrazinylamine or a phenylamine.

In the first stage of the process, a phenyl chloroformate and in particular 4'-nxtrophenyl chloroformate is preferably used. However, it is also possible to work with other phenyl chloroformates, such as 2,4-dinitrophenyl chloroformate or 4-trifluoromethylphenyl chloroformate. The first process stage is carried out in an inert solvent which remains liquid at the low temperatures used. Examples of such solvents are tetrahydrofuran or diethyl ether. The reaction is conducted at about -80 to about -40 ⁰ C, preferably about -75 to about -65 ⁰ C is performed.

Any alkyllithium can be used as an alkyllithium compound, containing 1 to 7 carbon atoms. n-Butyllithium is preferred as alkyllithium.

In the above method for carrying out the present reaction are added at step (a) the alkyl lithium at a temperature of about -80 to -40 ⁰ C over a period of about 10 to 15 minutes to a solution of the amide in the particular solvent and the mixture is stirred the mixture obtained in this way then for about 30 minutes at this low temperature. The phenyl chloroformate dissolved in the respective solvent is then added at this low temperature over a period of about 15 to 20 minutes and the mixture thus obtained is then stirred in the cold for about 2 to about 6 hours.

In the second part of the step (a) dissolved amine over a period of about 5 to about 20 minutes at a temperature of about -80 to about -40 ⁰ C to which one gives in an inert solvent such as tetrahydrofuran, diethyl ether or toluene, after

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urethane obtained in the first stage. The temperature of the reaction mixture is then allowed to rise and the mixture is heated to about 50 to 100 ^° C., preferably about 50 to 65 ^° C., for about 4 to about 24 hours to form the desired benzoylurea.

In the preferred process for carrying out the reaction according to process step (b) above, the reactants are combined in a different order. As a first step by treating the benzamide with a C.-C ₇ alkyllithium in an inert solvent at a temperature from -80 to -40 ⁰ C to form the corresponding lithium salt. This stage is carried out in exactly the same way as the first stage of the first embodiment of the present process, namely process stage (a). Again, n-butyllithium is preferably used as the alkyllithium. The lithium salt thus obtained is then treated at -80 to -40 ⁰ C with a carbamate, which is a reaction product of a phenyl chloroformate and an amine of formula RNH. ₂ The reaction mixture is then stirred for about 0.5 to 6 hours at a low temperature, then allowed to warm to 40 ⁰ C, the Gemsich to form the desired Benzoylharnstoffs to a temperature of about 20 and holding this temperature for about 1 to 24 hours. Suitable solvents for this process stage are tetrahydrofuran, diethyl ether or toluene.

The invention also relates to new 1- (mono-o-substituted-benzoyl) -3- (substituted-pyrazinyl) ureas of formula II

• - · c v

> C - N - C - NA _x ^

X V

HH

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A 'means bromine, chlorine or methyl,

R hydrogen, halogen, C - C, cycloalkyl, halogen

(C ₁ -C-) alkyl, nitro, cyano,

R ³

- ^(CH ₂ ^} p ~ \ / \,

or Nap> is ethyl,

R is hydrogen, halogen, methyl, ethyl, cyano or

Is halogen (C.-C ") alkyl,

with the proviso that the substituents R and R cannot be hydrogen at the same time,

R hydrogen, halogen, halogen (C ₁ -C.) Alkyl,

Cj-C.-alkylthio, C ₁ -C.-alkylsulphinyl, C ₁ -C.-alkylsulphonyl, nitro, cyano, phenoxy or phenyl,

q is 0, 1, 2 or 3,

ρ stands for 0 or 1 and

X ¹ for

0 0

U Il

-0-, -S-, -S- or -S-

Il

stands.

809383 / Ό713

These compounds of the formula II are prepared by reacting the compounds of the formulas

R ^S

J \ » _{9 B} , 3 1 H

tr · C — R and ^R % s ·

Q "IQ

wherein R and R are amino or isocyanate, first forms a ureido bridge and the compounds possibly obtained thereafter, in which X ^{1 is} -S-, then oxidized, if one would like to have compounds of the formula TI in which X ^{1 is}

0 0

Il. Il

-S- or -S-

Il

0 stands.

Those compounds from the above formula II in which

A ^{1 is} bromine, chlorine or methyl.

Hydrogen, halogen, C, -C _fi cycloalkyl, halogen

<™ \ - \ _ y ■ - * - ζ '

or naphthyl.

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R is hydrogen, halogen, methyl, ethyl or halogen

Represents (C ₁ -C ₂ ) alkyl,

with the proviso that the substituents R and R cannot be hydrogen at the same time,

R ⁸ halogen, halogen (C -, - C ₄ ) alkyl, C ₁ -C _{6 alkyl, C 1 -C 4}

Alkoxy, C ^^ - alkylthio, C ^^ - alkylsulfinyl, C ₁ alkylsulfonyl, nitro or cyano means

q stands for 0, 1, 2 or 3,

ρ stands for O or 1 and

X ^f for

0 0 -Ο-, -S-, -S- or -S-

It

0 stands.

Those compounds of the above formula II are more preferred, at them

A ^{1 is} bromine, chlorine or methyl,

R halogen, halogen (C, -C ₃ ) alkyl, C ₃ -C, cycloalkyl,

or - (CH) »^

- «-« ν / ς

means,

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R is hydrogen, halogen, halogen (C ₁ -Cp) alkyl or

Represents methyl,

R hydrogen, halogen, halogen (C ₁ -Cp) alkyl,

Is Cj-Cp-alkyl or C ₁ -Cp-AlkOXy,

g stands for 0, 1 or 2,

ρ stands for O or 1 and

X ^{1 represents} -O- or -S-.

Most preferred are those. Compounds of the above formula II in which

A ^{r is} bromine, chlorine or methyl _f

R ⁶ for

- (CH ₉ ) - «^ f or -cyclohexyl

stands,

ο
R halogen, halogen (C ₁ -C ₉ ) alkyl, C.-C ^ -alkyl or

means.

ρ stands for O,

q stands for 1 or 2 and

R is hydrogen or methyl,

with the proviso that the substituent R must be chlorine or bromine in the p-position if R is hydrogen and q is stands.

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In the above formula II, halogen becomes fluorine, chlorine and bromine Understood.

The indication C -.- Cj.-Cycloalkyl refers to cycloalkyl with 3 to 6 carbon atoms in the ring, examples of which are cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

The term halogen (C ₁ -C.) Alkyl relates, for example, to trifluoromethyl, brominethyl, 1,1-difluoroethyl, pentafluoroethyl, 1,1,2,2-tetrafluoroethyl, chlorodifluoromethyl, trichloromethyl, 2-bromoethyl, chloromethyl, 3 -Bromopropyl, 4-bromobutyl, 3-chloropropyl or 3-chlorobutyl.

Examples of halogen (C ₁ -C ") alkyl are trifluoromethyl, bromomethyl, chloromethyl, 1,1-difluoroethyl, pentafluoroethyl, 1,1,2,2-tetrafluoroethyl, chlorodifluoromethyl, trichloromethyl or 2-bromoethyl.

C.-C ₂ -alkoxy is understood to mean methoxy or ethoxy.

C.-C.-alkoxy means methoxy, ethoxy, propoxy, isopropoxy, Understood n-butoxy, s-butoxy, isobutoxy or t-butoxy.

The indication C.-C "-Alkylthio refers to methylthio or Ethylthio.

C 1 -C ₄ -alkylthio is understood to mean methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, s-butylthio or t-butylthio.

Examples of C ^ -C.-alkylsulphonyl are methylsulphonyl, ethylsulphonyl, n-propylsulfonyl, isopropylsulfonyl or butylsulfonyl.

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Examples of Cj-C ^ -alkylsulfinyl are methylsulfinyl, ethylsulfinyl, n-propylsulfinyl, isopropylsulfinyl or butylsulfinyl.

Individual examples of new compounds falling under the above formula II are the following:

1- (2-bromobenzoyl) -3- / 5- (alpha, alpha, alpha-trifluoro-m-toiyI) 6-ynethyl-2-pyrazinynyurea f,

1- (2-methylbenzoyl) -3- / 5- (alpha, alpha, alpha-trifluoro-p-toiyI) -6-ynethyl-2-pyrazinyl / urea f,

1- / 5- (alpha, alpha, alpha-trifluor-rti-tolyl) -2-pyrazinyl / -3- (2-chlorobenzoyl) urea,

1- (5-chloro-6-methyl-2-pyrazinyl) -3- (2-chlorobenzoyl) urea, 1- (5-Broiu-6-ethyl-2-pyrazinyl) -3- (2-methylbenzoyl) urea,

1- (2-bromobenzoyl) -3- / 5- (alpha, alpha, alpha-trifluoro-p-tolyl) -2-pyraζ inyl / harηsto f f,

1- (6-bromo-5-cyano-2-pyrazinyl) -3- (2-chlorobenzoyl) urea,

1- (5-Cyclopentyl-6-methyl-2-pyrazinyl) -3- (2-methylbenzoyl) -herea,

1- / 5- (2-bromoethyl) -2-pyrazinyl _ / - 3- (2-bromobenzoyl) urea, 1- (5-Benzyl-6-chloro-2-pyrazinyl) -3- (2-methylbenzoyl) urea. 1- (2-chlorobenzoyl) -3- (5-phenylthio-2-pyrazinyl) urea, 1- (2-bromobenzoyl) -3- (6-methyl-5-benzyl-2-pyrazinyl) urea,

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1- (2-chlorobenzoyl) -3- / 5- (Ί-naphthyl) -2-pyrazinyl / urea, 1- (2-chlorobenzoyl) -3- (6 ~ cyano-5-phenyl-2-pyrazinyl) urea, 1- (2-chlorobenzoyl) -3- (5-nitro-2 ~ pyrazinyl) urea,

1-C2-chlorobenzoyl) -3- / 5- (4-chlorophenylthio) -6-methyl-2-pyrazinyl / urea ,

1- (2-methylbenzoyl) -3- / 5- (4-bromophenoxy) -2-pyrazinyl) urea.

The new compounds of the formula IT are insecticidal, because they disrupt the growth of the insects that respond to them. The compounds appear to be part of the insect molting process disturb them so that they are killed. The compounds develop their effect on insects because the insects do so Digesting compounds, for example eating the leaves treated with the respective active ingredients or the foliage or other parts of their usual habitat, such as Water, manure or similar vehicles that have been treated with active ingredient, ingest. Because of this behavior, the present compounds especially for controlling insects in the larval state.

The new compounds of the formula II, surprisingly, also show a systemic effectiveness in plants that are produced with them have been treated. If one of the new insecticidally active compounds is applied to an old leaf of a plant, for example a soybean plant, then the insecticidally active compound will be present in the soybean plant the new growth of the plant and even transferred into the main stem of the plant. However, there is no systemic one Transfer of the insecticidally active compound when using this compound treats the roots of soybeans or other plants.

803803/0713

- yr -

It was also found that certain compounds that come under the formula II are also effective ovicidally. This acts it is those compounds of the formula II in which

A ^{r means} bromine or chlorine,

R is hydrogen, tri fluorine thyl or

is,

R is hydrogen, chlorine, methyl or triformethyl

display,

R is hydrogen, halogen, methoxy, trifluoromethyl

or is phenyl,

q stands for 0 or 1 unä

ρ stands for O.

The new compounds of formula II are better known per se Way made.

To prepare the compounds of the formula II, a corresponding 2-aminopyrazine is reacted with a 2-substituted-benzoyl isocyanate, whereby the corresponding 1- (mono-o-substituted-benzoyl) -3- (substituted-pyrazinyl) urea is obtained. The reaction is conducted at about O C to 7O performed ^{0 0} C, conveniently at about room temperature, for a time sufficient to substantially complete the reaction time period. The implementation time required for this depends on the reactants used in each case and can be of the time during which

809603/0713

the reactants are added and mixed together for up to 48 hours. The implementation is carried out using a suitable solvent carried out. For this purpose, inert solvents come into question, which are not used in any of the reactions taking place react with the isocyanates used. Examples of such solvents are ethyl acetate, dimethylformamide, tetrahydrofuran, Dioxane, acetonitrile, benzene, toluene, chloroform or methylene chloride.

An example of such a manufacturing method is described below.

2-Chlorobenzoyl isocyanate is allowed to react with 2-amino-5- (4-bromophenyl) -6-methylpyrazine in cold ethyl acetate. The reaction mixture is stirred at room temperature overnight. The resulting product is isolated by filtration and _r by recrystallization from a suitable solvent such as ethanol, cleaned. The product obtained in this way melts at about 230 to 232 ^° C. Based on NMR and IR spectra and an elemental analysis, it is 1- (2-chlorobenzoyl) -3- / 5- (4-bromophenyl-6-methyl) -2-pyrazinyl / urea.

To prepare a compound of the formula II, a 2-substituted-benzamide can also be reacted with a 2-pyrazinyl isocyanate in a suitable solvent while observing the reaction conditions described above and the reaction times mentioned. By reaction of 2-chlorobenzamide 5-Trifluormethylpyrazin-2-yl isocyanate passes to urea as for example, 1- (2-chlorobenzoyl) -3- (5-trifluoromethyl-2-pyrazinyl), which melts at about 219-220 ⁰ C.

Some of the required starting materials are commercially available, while the others can be produced by processes known per se.

809883/0713

For the preparation of the 2-substituted-benzoyl isocyanate sets for example, corresponding 2-substituted-benzamides are used by the process described in J. Org. Chem. 27, 3742 (1962) around.

The benzamides required in the present process, Phenyl chloroformates, anilines, aminopyridines and lithium compounds are likewise either commercially available or can be prepared by processes known per se. The pyrazines and the benzopyrazines (quinoxalines) can be used in the usual manner getting produced.

One of the required intermediates, namely 2-amino-5-chloropyrazine, can be prepared by the method described in J. Org. Chem. 29, 2491 (1964). To this end, methyl 2-amino-3-pyrazinyl carboxylate is used with chlorine in acetic acid to give methyl 2-amino-5-chloro "3 ~ pyrazinyl carboxylate. By hydrolysis of this ester with aqueous sodium hydroxide, 2-amino-3-carboxy-5-chloropyrazine is obtained Heat in tetrahydronaphthalene and decarboxylate gives the desired 2-amino-5-chloropyrazine.

Another intermediate, namely 2-amino-5,6-dichloropyrazine, can be prepared by reacting 2-amino-6-chloropyrazine with N-chlorosuccinimide in chloroform to form a mixture from 2-amino-5,6-dichloropyrazine, 2-amino-3,6-dichloropyrazine and 2-amino-3,5,6-trichloropyrazine is obtained. By subsequent säulenchroniatographi see separation of this mixture leads to the desired 2-amino-5,6-dichloropyrazine.

The 2-amino-5-phenylpyrazine required in the present process can, according to Rec. Trav. Chim. 92, 455 (1973) and that therein mentioned literature.

Other 2-amino-5 (or 6) -substituted-pyrazines that can be used for Production of the new end products of the formulas I or II are suitable,

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can be formed using oxime derivatives of certain ketones. 2-oxopropanal-i-oxime and 2-oxobutanol-1-oxime can for example from ethyl acetoacetate or ethyl propioacetate according to Chem. Ber. 11, 695 (1878). Other Oximes serving as intermediates can be prepared from ketones such as acetophenone, 2,4-dimethyl acetophenone, p-chloroacetophenone and Benzyl methyl ketone, according to the in Chem. Ber. 20, 2194 (1887). Other oximes again can be derived from ketones such as p-methoxypropiophenone, p-bromobutyrophenone, p-bromopropiophenone and methylneopentyl ketone, according to the in J. Am. Chem. Soc. 51, 2262 (1929) indicated method.

Another Oxiiu serving as an intermediate product can be converted from t-butyl methyl ketone to t-butyl glyoxal according to J. Am. Chem. Soc. 61, 1938 (1939). This t-butylglyoxal is then reacted in aqueous solution at pH 4 to 5 with acetone oxime (commercially available) for about 2 days at about room temperature. By subsequently working up the reaction mixture by extraction with ether and isolating the t-Butylglyoxaloxims from the ether extract leads to colorless needles melting at about 50 to 52 ⁰ C.

The 2-amino-5-methylpyrazine required as an intermediate is prepared in stages starting from 2-oxopropanal-i-oxime. To do this, this oxime is first mixed with aminomalonic acid nitrile toylate (prepared according to J. Am. Chem. Soc. 88, 3829 (1966j_ / zu 2-Amino-3-cyano-5-methylpyrazine-1-oxide. Then it becomes this obtained pyrazine-1-oxide reacted with phosphorus trichloride, which leads to 2-amino-3-cyano-5-methylpyrazine. This 2-amino-3-cyano-5-methylpyrazine is then hydrolyzed with aqueous sodium hydroxide to form 2-amino-3-carboxy-5-methylpyrazine. Decarboxylation of this compound in tetrahydronaphthalene gives the desired 2-amino-5-methylpyrazine.

809883/0713

Following the same general procedure and starting with 2-0xobutanal-1-oxime 2-amino-5-ethylpyrazine can also be produced.

Another pyrazine intermediate, namely 2-amino-5- (4-bromophenyl) -6-methylpyrazine, can be started from 1- (4-bromophenyl) -1,2-propanedione-2-oxime produce, this oxime according to the in J. Am. Chem. Soc. 51, 2262 (1929) Procedure forms. The oxime is first nitrile tosylate with aminomalonic acid reacted, whereupon the substituted pyrazine-1-oxide obtained as product according to the in J. Org. Chem. 38, 2817

(1973) described method with phosphorus trichloride in tetrahydrofuran implements. The 2-amino-3-cyano-5- (4-bromophenyl) -6-methylpyrazine obtained in this way is then hydrolyzed in sodium hydroxide and ethylene glycol, whereupon this is done 2-amino-3-carboxy-5- (4-bromophenyl) -6-ynethylpyrazine formed decarboxylated by heating in tetrahydronaphthalene. on this leads to 2-amino-5- (4-bromophenyl) -6-methylpyrazine.

Another intermediate, namely 2-amino-5,6-dimethylpyrazine, is made from 2-chloro-5,6-dimethylpyraζin, which, in turn, according to the in J. Am. Chem. Soc. 74, 1580-1584 (1952).

Other pyrazine intermediates can be prepared starting from 2,5-dichloropyrazine, which can be formed according to the process described in J. Org. Chem. 29, 2491 (1964). This 2,5-dichloropyrazine can be used as starting material for the preparation of the phenoxy- or phenylthio-substituted-pyrazines or the corresponding substituted phenoxy- or phenylthio-substituted-pyrazines required as intermediates. To this end, 2,5-dichloropyrazine is reacted with one equivalent of phenoxide ion or thiophenoxide ion in a suitable solvent, such as ethanol, t-butanol, dimethylformamide or acetonitrile, at about 0 ^° C. to about 120 ^° C., whereby the corresponding 2- Obtained chloro-5-phenoxy- (or -phenylthio) pyrazine. This 2-chloro-5-phenoxy (or-phenylthio) -

& ΰ 9-8 8-3- / 0.WS ^

pyrazine can be converted to the corresponding 2-amino-5-phenoxy (oderphenylthio) pyrazine, by allowing it sufficient at about 150 to 200 ⁰ C in a high pressure reaction vessel via a substantially complete conversion of

Reacts time with ammonium hydroxide. The t

2-Amino-5-phenoxy (or-phenylt, hio) pyrazine is then used for manufacture the 1- (Substituierhen-benzoyl) -3- / 5-phenoxy (or phenylthio) -2-pyrazinyl / ureas used. In the same way, homologues of phenoxy or phenylthio compounds can also be found produce.

The 2-chloro-S-pbenylthiopyrazine required as an intermediate or a corresponding homologue thereof can be obtained using oxidizing agents such as peracetic acid or m-chloroperbenzoic acid, sum corresponding ader! Oxidize intermediate 2-chloro-5-phenylsulfonylpyrazine or 2-chloro-5-phenylsulfonylpyrazine. For example, acetic acid, chloroform or methylene chloride are used as solvents for this purpose. The oxidation is expediently carried out at temperatures between about 20 and 7O ⁰ C.

Substituting the above-obtained 2-chloro-5-phenylsulfonylpyrazin or 2-chloro ~ 5-phenylsuli "inylpyrazin then with ammonia or ammonium hydroxide in a high pressure reaction vessel at about 100 to 200 ⁰ C in order, then we obtain the intermediate products 2-A? nino-5-phenylsulfonylpyrazin or 2-amino-5-phenylsulfinylpyrazin. the purpose applied reaction conditions are, depending on the chemical structure of Phenylsulfony grouping or different the Phenylsulfinylgruppierung! "

Also the 2-aminoquinoxalines, the simply aminobenzopyrazines can be produced by known methods. The preparation of 2-aminoquinoxaline ex 'follows, for example Reacting the commercially available 2-chloroquinoxaline with Ammonia in a suitable solvent, such as ethanol, at water bath temperature.

609883/0713 ORIGINAL INSPECTED

Other quinoxalines required as starting materials are used as a starting point made of o-phenylenediamines, which are commercially available are or can be prepared in a manner known per se. "■

Some of the non-commercially available o-phenylenediamines can be prepared from the corresponding dinitroanilines by hydrogenation. To this end, sets of anhydrous hydrazine in the presence of 5% ruthenium on carbon (Engelhard Industries) in a suitable solvent, such as commercial absolute ethanol, at about 55 to 70 ⁰ C in order. S-cyano-S-nitro-p-phenylenediamine can then be prepared, for example, by selectively hydrogenating 4-cyano-3,5-dinitroaniline in the presence of 5% ruthenium-on-carbon in ethanol as solvent together with anhydrous hydrazine. Using the same general process, 3-nitro-5-trifluoromethyl-o-phenylenediamine can also be prepared from 2,6-dinitro-4-trifluoromethylaniline.

Other o-phenylenediamines that are used in the manufacture of quinoxaline intermediates suitable, which you need for the synthesis of the new compounds of formula I, can by reduction of commercially available o-nitroanilines using 5% palladium on carbon catalyst in a low pressure hydrogenation apparatus getting produced. Appropriate hydrogenation of 2-nitro-4-trifluorom.: Thy! Aniline gives, for example 4-trifluoromethyl-o-phenylenediamine.

2-amino-6-chloroquinoxaline or 2-amino-7-chloroquinoxaline can produced by known methods, and for this, reference is made to, for example, The Chemistry of Heterocyclic Compounds. Condensed Pyridazine and Pyrazine Rings, Part III, Quinoxalines, Chapter XXIVff, page 203ff, by J. C. E. Simpson / Arnold Weissberger, Consulting Editor, Interscience Publisher, Inc., New York (1953j_ / referenced. An example of such The manufacturing process is as follows:

809883 / G713

It reacts 3,4-diaminochlorobenzene with glyoxylic acid, whereby a mixture of 6-chloro-2-hydroxyquinoxaline and 7-chloro-2-hydroxyquinoxaline is obtained. By converting this mixture with Phosphorus oxychloride leads to a mixture of 2,6-dichloroquinoxaline and 2,7-dichloroquinoxaline. If you leave this mixture react with anhydrous ammonia in a suitable solvent, preferably dimethyl sulfoxide, then one obtains a Mixture of 2-amino-6-chloroquinoxaline and 2-amino-7-chloroquinoxaline.

The invention is further illustrated by the following examples.

B e 1 s ρ i e 1 1

1- (2,6-Dichlorberizoyl) -3- / 6-methyl-5- (4-bromophenyl) -2-pyraziny.l / -

urea

A solution of 304 mg of 2,6-dichlorobenzamide and 25 ml of dry tetrahydrofuran is placed in a 50 ml three-necked round bottom flask. Under mechanical stirring and under nitrogen, the solution is then cooled in a dry ice-acetone bath to about -72 ⁰ C. The solution thus obtained is then treated with 0.6 ml of η-butyllithium over a period of 5 minutes. After completion of the addition, the reaction mixture is further stirred for 30 minutes at about -72 ⁰ C. A solution of 268 ml of 4-nitrophenyl chloroformate in 8 ml of dry tetrahydrofuran is then added dropwise to the mixture over a period of 15 to 20 minutes. A pale yellow solution forms. After completion of the addition, the reaction mixture is stirred for 30 minutes at about -72 ⁰ C, so as to obtain a colorless solution. Then, to set the cooling bath in such a way that the temperature is raised to -40 to -30 ⁰ C, and stirred for a further 3 hours. Then the reaction mixture is cooled to about -72 ⁰ C and treated dropwise over a period of 1O minutes with a solution of 351 mg

809883/0713

2-Amino-5- (4-bromophenyl) -6-methylpyrazine in 6 ml of dry tetrahydrofuran is added. The cooling bath is then removed and the mixture is allowed to come to room temperature. ^{The mixture is then heated to 50 °} C. for 16 hours to end the reaction. The solvent is then removed in vacuo and the residue is taken up in ethyl acetate. The ethyl acetate solution is washed five times with aqueous sodium carbonate solution and twice with salt water. The solvent is evaporated again, the residue is dissolved in 2 ml of tetrahydrofuran and the solution is chromatographed on silica gel using a 4: 1 mixture of benzene and tetrahydrofuran. The product obtained in this chromatography is dissolved in tetrahydrofuran, whereupon the solution is concentrated to an oil under Vaki uii. Ether is added to the oil and the resulting solution is cooled. In this way, a total of 240 mg of product are obtained in the form of two harvests. By crystallizing this product from tetrahydrofuran ether, 132 mg of material which melts at 225 to 227 ° C. is obtained. A further 69 mg of product are obtained from the filtrate by preparative thin-layer chromatography.

Example 2 1- (2,6-dichlorobenzoyl) -1- / 5- (4-chlorophenyl) -2-pyraziny_l / urea f

The procedure described in Example 1 is repeated using 273.5 mg of 2-amino-5- (4-chlorophenyl) pyrazine in place of 2-amino-5- (4-bromophenyl) -6-methylpyrazine. In this way, 222 mg of the title compound, which melts at 245 to 249 ^° C., are obtained.

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ORIGINAL INSPECTED

Example 3

1- (2,6-dichlorobenzoyl) -3- / 5- (3-trifluoromethylphenyl) -6-methyl-2-

pyrazinyl / urea

The procedure described in Example 1 is repeated using 336.8 mg of 2-amino-5- (3-trifluoromethylphenyl) -6-methylpyrazine in place of 2-amino-5- (4-bromophenyl) -6-methylpyrazine. The product coming from the column filled with silica gel is subjected to preparative thin-layer chromatography, whereby a viscous oil is obtained which crystallizes to a white solid on standing. The solid is treated with cold ether and then filtered off, resulting in 62 mg of a white product which melts ^{at 182 to 185 ° C. as the first crop.} The filtrate is allowed to evaporate in a hood for concentration, yielding a yellow oil. The crystallization of this oil from ether leads to 102 mg of a white solid as a second crop. The total yield is 164 mg.

Example 4
1- (2,6-dichlorobenzoyl) -3- (6- trifluoromethy 1-2-pyrazinyl) urea

The procedure described in Example 1 is carried out using 217 mg of 2-amino-6-trifluoromethylpyrazine in place of 2-amino-5- (4-bromophenyl) -6-methylpyrazine repeated. The product obtained is worked up as described in Example 3. That at the oil obtained from preparative thin-layer chromatography crystallizes on standing at room temperature. The raw solid is treated with cold ether, and the crystalline solid thus obtained is filtered off. In this way arrives to 144 mg of product which melts at 188 to 192 ° C.

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Example 5 1- (2,6-Dichlorobenzoyl) -3- (3-trifluoromethylphenyl) urea

A solution of 0.912 g of 2,6-dichlorobenzamide in 75 ml of dry tetrahydrofuran is placed in a 250 ml three-necked round-bottomed flask. The solution is cooled with an Trockeis-acetone bath to about -72 ⁰ C. 1.8 ml of n-butyllithium solution are added to the reaction mixture over a period of 5 minutes. Then the reaction mixture is allowed to stand for 30 minutes at -75 to -70 ^0C. A solution of 0.804 g of 4-nitrophenyl chloroformate in 24 ml of dry tetrahydrofuran is then added at a temperature of about -72 ° C. over a period of 30 minutes. The mixture is then left to stand in the cold for a further 30 minutes, during which it becomes colorless. The solution is then warmed to -40 ⁰ C and held for 2.75 hours at this temperature. The mixture is then cooled again to -72 ⁰ C and treated over a period of 10 minutes with a solution of 0.64 g of 3-aminobenzotrifluoride in 25 ml of dry tetrahydrofuran. The solution is then allowed to room temperature kommon what they are heated 16 hours at 50 ⁰ C. The solvent is removed and the residue is dissolved in 10 ml of ether. The solution is washed with 1 normal sodium carbonate solution, dried over magnesium sulfate and evaporated to remove the solvent. By finally treating the residue with ether leads to 0,6 g of a woißen crystalline solid melting at about 200 ⁰ C.

Analysis:

Calculated: C, 47.77; H 2.41; N 7.43; Found: C, 46.85; H 2.62; N 7 _r 2O.

809883 ^ 0713 ORIGINAL INSPECTED

Example 6 1- (2,6-dichlorobenzoyl) -3- (4-trifluoromethylphenyl) urea

A solution of 0.912 g of 2,6-dichlorobenzamide in 75 ml of dry tetrahydrofuran is added all at once at a temperature of -30 ⁰ C with 1.8 ml of 2.4 molar n-Butyllithiumreagenz. Then added to the reaction mixture over a period of 10 minutes at -40 ⁰ C with a mixture cius 0.804 g of 4-nitrophenyl chloroformate in 25 ml of dry tetrahydrofuran. The resulting pale yellow solution is stirred until it becomes colorless (about 5 minutes). Subsequently, maintaining the solution at -35 to -30 ⁰ C and mixed them over a period of 5 minutes with a solution of 0.8 g of 4 ~ aminobenzotrifluoride in 25 1 of dry tetrahydrofuran. The solution is then heated for 4 hours at reflux temperature (about 60 ⁰ C). The mixture is diluted with 300 ml of ether, washed five times with sodium carbonate solution, dried and the solvent removed. Recrystallization from hexane-Sther one arrives at O, 72 g of product (not sharp) melts at 205 ⁰ C.

Analysis:

Calculated: C, 47.75; H 2.39; N 7.43; found: C, 47.50; H 2.29; N 7.40.

Example 7 1- (2,6-Dichlorobenzoyl) -3- (4-trifluoromethylphenyl) urea

A solution of 1.9 g of 2,6-dichlorobenzamide in 75 ml of dry tetrahydrofuran is mixed with 5.0 ml of n-butyllithium ^{solution at a temperature of -70 to -7 5 ° C. in one go.} Subsequently treating the solution at a temperature of -75 ⁰ C for 0.5 hours with a solution of 3.26 g of N- (p-trifluoromethylphenyl} -0-

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- 29 * -

(p-nitrophenyl) carbamate in 25 ml of dry tetrahydrofuran. The solution is then allowed to come to -30 ° C., kept at this temperature for 1 hour and then allowed to come to room temperature. A subsequent thin-layer chromatographic examination shows that the desired product has formed. The product is isolated as described in Example 6, thereby obtaining 2.20 g of material (not sharp) melts at 2OO ⁰ C.

The following preparations describe the preparation of the substituted benzoyl isocyanates required as intermediates and pyrazines, which are required for the preparation of the new compounds of the formula II.

Her position 1 2-chlorobenzoyl isocyanate

This compound is according to the method described in J. Org. Chem. 27, 3742 (1962) described method produced.

First a solution of 10 g of 2-chlorobenzamide (commercially available available) formed in 100 ml of methylene chloride. The solution obtained is then treated very slowly with 25 ml of oxalyl chloride. The mixture is refluxed overnight. The reaction mixture is then cooled and filtered, whereupon the filtrate is used to remove the solvent present Evaporated ethylene chloride. The resulting oily residue is identified by the IR spectrum as 2-chlorobenzoyl isocyanate and used for the preparation of the new compounds of the formula I without purification.

809883/0713

Following the same general procedure as in preparation 1 above and starting from 2-MGthylbenzamide or 2-bromobenzamide, Both of which are commercially available, the following additional compounds are prepared by their IR spectra be identified:

2. 2-methylbenzoyl isocyanate in the form of an oil.

3. 2-bromberizoyl isocyanate in the form of an oil.

Preparation of 4 2-amino-5-chloropyrazine

This connection is established in stages. The first stage is after that in Ann. 660, 98-103 (1962) carried out.

For this purpose, a device of 7.5 g of 2-amino-3-carboxypyrazine, 8.9 g of 1-methyl-3-p-tolyltriazine and 250 mg of tetrahydrofuran is heated to reflux temperature for about 4 hours. The reaction mixture is then cooled and filtered, discarding the solid that remains on the filter. The filtrate is evaporated to dryness in vacuo and a small amount of ethyl ether is added to the residue. The solid that separates out is collected. It weighs approximately 7 g and melts at about 166 to 169 ⁰ C. Because of an IR spectrum is this is to give methyl 2- ^ mino-3-pyrazinylcarboxylat.

In the next stage the mixture is stirred a mixture of 2.8 g of methyl 2-amino-3-pyrazinylcarboxylat, 100 ml of water and 23 ml of glacial acetic acid at about 40 ⁰ C and passed into the resulting mixture for about 25 minutes, a water-free chlorine. while maintaining the temperature of the P.eaktionsgemisches to about 35 to 40 ⁰ C. The reaction mixture is then cooled and filtered. The solid obtained is 1 hour in a mixture of 30 ml of water and

809883/0713 ORIGINAL INSPECTED

4.6 g of sodium sulfite were stirred and the whole was filtered. The collected solid is in a mixture of ice and water stirred, whereupon it is filtered again. Based on an NMR spectrum, this solid is methyl 2-amino-5-chloro-3-pyrazinyl carboxylate. The material is used without further purification.

According to the method described in J. Org. Chem. 29, 2491 (1964), the above methyl ^ -amino-S-chloro-S-pyrazinylcarboxylate first hydrolyzed and then decarboxylated.

For this purpose, a mixture of 1.6 g of methyl 2-amino-5-chloro-3-pyraziriylcarboxylate and 50 ml of 2 normal aqueous sodium hydroxide is heated to reflux temperature for about 1.5 hours. The reaction mixture is then cooled and filtered. The collected solid is dissolved in 25 ml of hot water, the solution is filtered and the filtrate is acidified with concentrated aqueous hydrochloric acid. The solid which separates out is filtered off and dried. It weighs 1.3 g and melts at about 177 ^° C. with decomposition. Based on an IR spectrum, it is 2-amino-3-carboxy-5-chloropyrazine. This compound is used for the next step without further purification.

A mixture of 500 rag 2 - / - mino-3-r: arboxy-5-chloropyrazine and 9 ml of tetrahydronaphthalene is heated to reflux temperature for about 1 hour. The reaction mixture is then cooled and filtered. The solid obtained is washed with hexane. The solid melts at about 121 to 123 ^° C. with decomposition, and based on an NMR spectrum it is 2-amino-5-chloropyrazine.

8G9883 / G713

Preparation of 5 2-amino-5,6- dichloropyrazine

A mixture of 5 g of 2-Aminc-6-chloropyrazine (commercially available), 10.3 g of N-chlorosuccinimide and 100 ml of chloroform is heated for about 1 ₇ 5 hours at reflux temperature. The reaction mixture is cooled and filtered, the solid remaining in the filter being discarded. The filtrate is evaporated and the residue is washed with water and hot aqueous sodium bisulfite solution. The solid formed during this treatment is filtered off. This solid is then chromatographed on a column filled with 5 × 8 mia pellets of a copolymer of styrene and divine benzene using chloroform as the solution. ^c ; solution liquid and eluent. This chromatography gives the following three compounds:

Compound 1 with a melting point of about 132 to 135 ⁰ C, which is identified as 2-amino-3,6-dichloropyrazine.

Compound 2 with a melting point of about 132 to 134 ⁰ C, which is identified as 2-amino-3,5,6-trichloropyrazine.

Compound 3 with a melting point of about 143 to 144 ⁰ C, which is identified as the desired 2-amino-5,6-dichloropyrazine.

Manufacturing (5th
2-amino-5-phenyl-6-methylpyrazine

This intermediate pyrazine is produced in a step-by-step process.

In the first stage, a mixture of 6.5 g of 1-phenyl-1,2-propanedione-2-oxime is stirred (commercially available) and 10.1 g of aminomalone

809883/0713

acid xltosylate in 60 ml isopropyl alcohol overnight at room temperature. The reaction mixture is then filtered to give 7 g of solid. This solid is based on an NMR spectrum around 2-amino-3-cyano-5-phenyl-6-methylpyrazine-1-oxide.

A mixture of 7 g of the prepared in the above manner pyrazine-1-oxide and 250 ml of tetrahydrofuran is cooled to about 0 ⁰ C and slowly treated with 40 ml Pbosphortrichlorid. After the addition has ended, the reaction mixture is stirred at room temperature overnight. The mixture is then concentrated in vacuo to a volume of about 50 ml, whereupon the concentrate is poured into 1 liter of a mixture of ice and water. The solid which then precipitates is filtered off. In this orphan one receives 1 g of 2 ~ ArrrLpo-3-cy3na-5-phenyl-6-methylpyraxir! ..

In the next stage, a mixture of 1 g of 2-amino-S-cyano-S-phenyl-S-methjlpyrazine (prepared as above), 50 ml of ethylene glycol and 500 mg of sodium hydroxide is heated to about 150 ^° C. for about 3 hours is cooled, mixed with water and neutralized to pH 5-7. The precipitated solid is collected. Based on an IR spectrum, it is 2-amino-3-carboxy-5-phenyl-6-methylpyrazine. This solid is used directly for the next process step.

500 mg of the carboxypyrazine prepared in the above manner heated for about 2 hours in 5 ml of tetrahydronaphthalene. The reaction mixture is cooled and hexane is added. The solid which precipitates out is filtered off. In this way one arrives at 470 mg of product which is due to an NMR spectrum and an IR spectrum around 2-amino-5-phenyl-6-methylpyrazine acts.

80988 3/0713

ORIGINAL INSPECTED

Following the same general procedure as in Preparation 6 and using the detailed oximes as starting materials, which according to the in J. Am. Chem. Soc. 51, 2262 (1929) other intermediate pyrazines are used. These pyrazines are identified by their NMR and IR spectra, and these are the following connections:

7. 2-Amino-5- (4-niethoxyphenyl) -6-methylpyrazine from 1- (4-methoxyphenyl) -1,2-propanedione-2-oxime.

8. 2-Amino-5- (4-chlorophenyl) -6-methylpyrazine from 1- (4-chlorophenyl) -1,2-propanedione-2-oxime.

9. 2-Amino-5- (4-bromophenyl) -6-methylpyrazine from 1- (4-bromophenyl) -1,2-propanedione-2-oxime,

10. 2-Amino-5- (4-n-butylphenyl) -6-methylpyrazine from 1- (4-n-butylphenyl) -1,2-propanedione-2-oxime.

11. 2-Amino-5- (alpha, alpha, alpha-trifluoro-m-tolyl) -6-methylpyrazine from 1- (alpha, alpha, alpha-trifluoro-m-tolyl) -1,2-propanedione-2-oxime.

12. 2-Amino-5- (4-biphenylyl) -6-methylpyrazine from 1- (4-biphenylyl) -1,2-propanedione-2-oxime.

13. 2-Amino-5- (4-fluorophenyl) -6-methylpyrazine from 1- (4-fluorophenyl) -1,2-propanedione-2-oxime.

14. 2-Amino-5- (alpha, alpha, alpha-trifluoro-p-toIyI) -6-methylpyrazine from 1- (alpha, alpha, alpha-trifluoro-p-tolyl) -1,2-propanedione-2-oxime.

15. 2-Amino-5- (4-ethylphenyl) -6-methylpyrazine from 1- (4-ethylphenyl) -1,2-propanedione-2-oxime.

809883/0713

16. 2-Amino-5-cyclohexyl-6-methylpyrazine from 1-cyclohexyl-1,2-propanedione-2-oxime.

17. 2-Amino-5- (4-methylthiophenyl) -6-methylpyrazine 1- (4-methylthiophenyl) -1, 2-

18. 2-Amino-6-methyl-5- (p-tolyl) pyrazine from 1- (p-tolyl) -1,2-propanedione-2-oxime.

Following the general procedure outlined in Preparation 6 using those given below Oximes, which according to Chem. Ber. 20, 2194 (1887), the following additional intermediates are prepared Pyrazines identified by their NMR and IR spectra:

19. 2-Amino-5- (2,4-xylyl) pyrazine from 2,4-xylylglyoxaloxime.

20. 2-Amino-5- (3,4-dichlorophenyl) pyrazine from 3,4-dichlorophenylglyoxaloxime.

21. 2-Amino-5- (alpha, alpha, alpha-trifluoro-m-tolyl) pyrazine from 3-trifluoromethylphenylglyoxaloxime.

22. 2-Amino-5- (p-tolyl) pyrazine from p-tolylglyoxaloxime.

23. 2-Amino-5- (4 - chlorophenyl) pyrazine from 4-chlorophenylglyoxaloxime.

24. 2-Amino-5- (4-ethy! Phenyl) pyrazine from 4-ethylphenylglyoxaloxime.

25. 2-Amino-5- (4-t-butylphenyl) pyrazine from 4-t-butylphenylglyoxaloxime.

26. 2-Amino-5- (4-bromophenyl) pyrazine from 4-bromophenylglyoxal.

809883/0713

Preparation 27 2-Amino-5- (4-bromophenyl) -6-ethylpyrazine

This intermediate pyrazine is produced in stages.

The first stage consists in converting 4-bromobutyrophenone according to the method described in J. Am. Chenu Soc. 51, 2262 (1929) Process to give 1- (4-bromophenyl) -1,2-butanedione-2-oxime which is identified by IR and NMR spectra.

In the second stage, the 1- (4-bromophenyl) -1,2-butanedione-2-oxiiri obtained in this way is reacted further by the general process described in Preparation 6, whereby 2-amino-5- (4- bromophenyl) -6 ~ ethylpyrazine, which is identified by IR and NMR spectra.

Manufacture 28 2-Aiuino-6-cyanopyrazine This intermediate product is manufactured in stages.

A mixture of 21 g of pyrazine-2-carboxamide, 85 ml of glacial acetic acid and 75 ml of 30 percent hydrogen peroxide is heated ^{to about 55 ° C. for about 35 hours.} The reaction mixture is cooled and filtered. The solid obtained in this way is extracted with n-butanol, the extracts being discarded. The insoluble in n-butanol solid is recrystallized from hot water, so as to obtain a white solid which melts at about 302-305 ⁰ C. The solid is identified as pyrazine-2-carboxamide-4-oxide by elemental analysis.

809883/0713

A mixture of 4 g of the pyrazine oxide obtained above in 40 ml of dimethylformamide, 12 ml of phosphorus oxychloride are rapidly added while cooling in an ice bath. The reaction mixture is poured into water and the aqueous mixture extracted with ethyl acetate, whereby the extracts are saved. More water is added to the aqueous layer and the aqueous mixture is extracted with hexane-ether. The ethyl acetate and hexane-ether extracts are combined and concentrated in vacuo to a residue. The residue is through Elemental analysis and IR spectrum as 2-chloro-6-cyanopyrazine identified, and this product is used for the next process step without further purification.

A mixture of 1 g is prepared as obtained in the above manner Chlorcyanopyrazins and 25 inl IDimethylsulfoxid and conducts then anhydrous ammonia in this mixture. The reaction mixture is stirred overnight and then poured into water. The aqueous mixture is extracted with ethyl acetate and the extracts are dried. The drying agent is filtered off and removing the solvent in vacuo leaving a solid to be identified by its IR spectrum is 2-amino-6-cyanopyrazine. This material is used for the preparation of compounds of the formula I without further purification.

Manufacture 29

2-Amino-6-trifluoromethylpyrazxn This intermediate is produced in stages.

According to the in Chem. Ber. 89, 1185 (1956) one first produces aminoacetamidine dihydrochloride. That further required 3,3-dibromo-1,1,1-trifluoropropanone is made after J. Am. Chem. Soc. 74, 3902 (1952) resulting process.

809883/0713

A mixture of 6.6 g of 3,3-dibromo-1,1,1-trifluoropropanone, 60 ml of water and 6.6 g of sodium acetate is heated to reflux temperature for about 10 minutes. The solution obtained is cooled and added dropwise to a solution of 6 g Aminoacetamidindihydrobromid in 90 ml of methanol, the mixture is cooled to about -30 ⁰ C, followed by adding a solution of 3.6 g Natrxumhydroxidplätzchen in 25 ml of water. The reaction mixture is stirred and gradually warmed ^{to about 20 ° C. over a period of about 2 hours.} The reaction mixture is then evaporated in vacuo to remove the methanol and the residue obtained is extracted with ethyl acetate. In this way, we arrive at 3.6 g of a product melting after recrystallization from a mixture of benzene and hexane at about 133 to 136 ⁰ C. Based on an NMR spectrum and an elemental analysis, this product is 2-amino-6-trifluoromethylpyrazine.

Analysis for C ₁ -H ₄ FN · calculated

C 36.82% • H 2.47 N 25.76

Preparation 30 2-Amino-5-trifluoromethylpyrazine

A solution of 18 g of 4,5-diamino-6-hydroxypyrimidine sulfate (commercially available) in 180 ml of aqueous 3 normal sodium hydroxide is prepared and cooled, whereupon the cooled mixture is mixed with 25.2 g of 3,3-dibromo-1, 1,1-trifluoropropanone added. The reaction mixture is stirred for about 48 hours at room temperature. The resulting precipitate is filtered off, dissolved in 140 ml of aqueous 60 percent sulfuric acid and heated for about 8 hours to about 135 ⁰ C. The Re-

809883/0713

found , 11% 37 , 17th 2 , 52 25th

action mixture is poured onto crushed ice, whereupon the aqueous mixture is neutralized with concentrated aqueous ammonium hydroxide. The solution is then washed with ethyl acetate extracted. The ethyl acetate extracts are evaporated to dryness in vacuo, whereupon the resulting residue is removed recrystallized from a mixture of benzene and hexane. In this way one arrives at 2.2 g of a product that is at melts about 118 to 122 ° C. This product is based on an NMR spectrum and an elemental analysis around 2-amino-5-trifluoromethylpyrazine.

Analysis for C ₅ H ₄ FN ₀ :

calculated found

C. 36.82% - 37.04% H 2.47 2.58 N 25.76 25.97

Manufacture 31

2-Amino-5-phenyl-6-trifluoromethylpyrazine This intermediate is produced in a stepwise manner.

According to the in J. Het. Chem. 10, 697 (1973) 1-phenyl-3,3,3-trifluoro-1,2-propanedione monohydrate is produced first here.

A solution of 1.8 g of 1-phenyl-3,3,3-trifluoro-1,2-propanedione monohydrate in 40 ml of methanol is cooled in an ice bath and treated with 2 g of aminoacetamidine dihydrobromide with stirring. With further stirring, 8.6 ml of aqueous 2 normal are then added Sodium hydroxide added. The reaction mixture is then stirred for about 2 hours at room temperature, whereupon it is stirred Stirring for about 4 hours under reflux temperature. That

809883/0713

- j & r-
-53-

The reaction mixture is cooled and washed with dilute aqueous Acidified hydrochloric acid. Then you add water and extract the mixture with 100 ml of ethyl acetate. The ethyl acetate extract is dried over anhydrous magnesium sulfate dried, whereupon the drying agent is filtered off and the filtrate is concentrated in vacuo. The residue obtained in this way is dissolved in chloroform and the solution is passed through a column filled with silica gel using chloroform chromatographed as the eluent. Got this way to 100 mg of material which is 2-amino-5-phenyl-6-trifluoromethylpyrazine acts.

Manufacturing 32

2-''-5- (4-bromophenyl) -6-chloropyrazine This compound is prepared in stages. step 1

A mixture of 37 g of 1- (4-bromophenyl) -1,2-propanedione-2-oxime, 34 g of the tosylate salt of ethylaminocyanoacetate and 750 ml of isopropanol is stirred for about 6 days at room temperature. A further 12 g of the above are then added to the reaction mixture Tosylate salt and stirred for a further 24 hours at room temperature. The reaction mixture is then added with a further 3 g of the tosylate salt and stir it for several days at room temperature. The reaction mixture is then cooled and the precipitated solid is filtered off. The solid is extracted with 2 liters of boiling ethyl acetate and filtered off. The filtrate is concentrated to about 900 ml in vacuo. The solution is filtered again and then cooled. The crystalline material that separates out becomes

809883/0713

2828893

filtered off. In this way one arrives at a material which melts at about 200 to 205 ° and which, due to its NMR spectrum around 2-amino-5- (4-bromophenyl) -3-carbethoxypyrazine-1-oxide acts. The yield is 11 g.

Level 2

A mixture of 60 ml of phosphorus oxychloride and 10 ml of dimethylformamide is mixed in small portions with 12.1 g of 2-amino-5- (4-bromophenyl) -3-carbefchoxypyrazine-i-oxide (prepared in the above manner) while stirring. After the reaction has ended, the reaction mixture is heated to reflux temperature for about 15 minutes, after which the excess phosphorus oxychloride is removed under reduced pressure. Ice is added very carefully to the residue, whereupon the mixture is made basic by adding solid sodium bicarbonate. The mixture is extracted with 800 ml of chloroform and the chloroform extract is dried over anhydrous magnesium sulfate. The drying agent is filtered off and the filtrate is evaporated to dryness in vacuo. The black solid that remains is extracted four times with 500 ml of boiling cyclohexane each time. The combined cyclohexane extracts are concentrated to a volume of about 300 ml. The beige solid which separates out here melts at about 151 to 153 ^° C., and based on an NMR spectrum it is 5- (4-bromophenyl) -3-carbethoxy-6-chloro-2- . [_ (Dimethylamino) methylene / imino »pyrazine. The yield is 10.5 g.

level 3

A mixture of 12 g of 5- (4-bromopheny 1) -S-carbethoxy-ö -chloro ^ - \ / _ (dimethylamino) methylene / imino ipyrazine (prepared in step 2) and 150 ml of aqueous 2N hydrochloric acid is stirred heated to reflux temperature for about 5 minutes, a white precipitate being formed. The mixture is cooled and about 50 ml of aqueous 1 normal sodium hydroxide solution are added. The mixture is filtered off,

809883/0713

and the resulting solid is washed on the filter with water. A sample of this solid obtained by recrystallization from ethanol melts at about 207 to 208 ^° C. Based on an NMR spectrum and an elemental analysis, this is 2-amino-5- (4-bromophenyl) -3-carbethoxy-6-chloropyrazine . The yield is 10 g.

Analysis for C ₁₃ H ₁₁₃₂

calculated found

C 43.79% 43.90%

H 3.11 3.33

N 11.78 11.59

Level 4

A mixture of 10 g of 2-amino-5- (4-bromophenyl) -S-chloropyrazine, 75 ml of dioxane, 75 ml of water and 8 g of sodium hydroxide cookies is briefly heated to reflux temperature, everything going into solution. The reaction mixture is then acidified with acetic acid and cooled. The resulting solid is filtered off and slurried in aqueous 1N hydrochloric acid, whereupon the solid contained therein is filtered off. After recrystallizing a sample of this from ethanol, the melting point is about 212 to 214 ^° C. Based on an NMR spectrum and an elemental analysis, it is 2-amino-5- (4-bromophenyl) -3-carboxy-6- chloropyrazine. The yield is 9 g.

Analysis for C ₁₁ H

calculated found

C 40.21
H 2.15
N 12.79

40, 10% 2, 23 12, 63

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- SG-

A mixture of 9 g of 2-amino-5- (4-bromophenyl) -S-carboxy-chloropyrazine and 50 ml of tetralin is heated to reflux temperature for about 15 minutes. The reaction mixture is cooled and treated with 75 ml of hexane. The precipitated solid is filtered off and washed with hexane. By subsequent recrystallization of this solid from ethyl acetate leads to a melting point at about 254-256 ⁰ C product. Based on an NMR spectrum, this is a 2-amino-5- (4-bromophenyl) -6-chloropyrazine. The yield is 4 g.

The following examples explain the preparation of the new compounds of the formula I.

Example 8

1- (2-chlorobenzoyl) -3- / 5- (4-bromophenyl) -6-methyl ~ 2-pyrazinyl / urea

A mixture of 2.6 g of 2-amino-5- (4-bromophenyl) -6-methylpyrazine in 100 ml of ethyl acetate is mixed with 2.0 g of 2-chlorobenzoyl isocyanate and stirred overnight at room temperature. The mixture is then filtered. The solid obtained in this way is recrystallized from ethanol, resulting in a material melting ^{at about 230 to 232 ° C.} Based on an elemental analysis and the NMR and IR spectra, it is 1- (2-chlorobenzoyl) -3- / 5- (4-bromophenyl) -6-methy1-2-pyrazynyl / urea.

Analysis for C ₁₉ H ₁₈₄₂

calculated found

C 51.20%
H 3.17
N 12.57

51 .03% 3 , 37 12th , 62

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- JMT -

Following the general procedure outlined in Example 8 the following compounds are prepared using appropriate starting materials, identified by elemental analysis, NMR spectrum and IR spectrum will:

8ä. 1- (2-chlorobenzoyl) -3- (5-trifluoromethyl-2-pyrazinyl) -urea rag having a melting point of about 219-220 ⁰ C, starting from 500 2-Aniino-5-trifluormethylpyrazin and 600 mg of 2-Chlorbenzoylisocyanat.

8B. 1- (2-chlorobenzoyl) -3- (5-phenyl-2-pyrazinyl) urea with a melting point of about 222 to 224 ⁰ C, starting from 1.0 g of 2-amino-5-phenylpyrazine and 1.0 g of 2- Chlorobenzoyl isocyanate.

8C. 1- (2-bromobenzoyl) -3- / 5- (4-bromophenyl) -6-methyl-2-pyrazinyl / urea having a melting point of about 220-222 ⁰ C, starting from 2.0 g of 2-amino-5 - (4-bromophenyl) -6-methylpyrazine and 2.0 g of 2-bromobenzoyl isocyanate.

8D - 1 - / 5- C4-bromophenyl) -6-methyl-2-pyrazinyl / -3- (2-methylbenzoyl) urea with a melting point of about 247 to 248 ⁰ C, starting from 1.0 g of 2-amino 5- (4-bromophenyl) -6-methylpyrazine and 1.0 g of 2-methylbenzoyl isocyanate.

8E. 1- (2-chlorobenzoyl) -3- / 5- (4-ethylphenyl) -6-methyl-2-pyrazinyl / urea with a melting point of about 212 to 214 ⁰ C, starting from 500 mg of 2-amino-5- ( 4-ethylphenyl) -6-methylpyrazine and excess 2-chlorobenzoyl isocyanate.

8F. 1- (2-chlorobenzoyl) -3- (6 ~ chloro-2-pyrazinyl) urea, having a melting point of about 202-203 ⁰ C, starting from 1.5 g of 2-amino-6-chloropyrazine, and 2.0 g 2 -Chlorobenzoyl isocyanate.

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- jfrflr <5T £

8G. 1- (2-chlorobenzoyl) -3- (6-trifluoromethyl-2-pyrazinyl) urea, having a melting point of about 179-180 ⁰ C, starting from 1.5 g of 2-Ämino-6-trifluormethylpyrazin and 1.6g 2-Chlorbenzoylisocyanat .

8H. 1- (2-chlorobenzoyl) -3- / 5- (4-methylphenyl) -2-pyrazinyl / urea with a dripping point of about 230-232 ⁰ C, starting from 600 mg of 2-amino-5- (4-methylphenyl ) pyraζin and 600 mg 2-Chlorbenzoyli socyanat.

81. 1- (2-chlorobenzoyl) -3- / 5- (4-chlorophenyl) -6-methyl-2-pyrazinyl / urea having a melting point of about 228-229 ⁰ C, starting from 600 mg of 2-amino-5 - (4-chlorophenyl) -6-methylpyrazine and 1.0 g of 2-chlorobenzoyl isocyanate.

8Y. 1- (2-chlorobenzoyl) -3- (6-methyl-5-phenyl-2-pyrazinyl) -urea with a melting point of about 221 to 222 ⁰ C, starting from 500 mg 2-Ämino-6-mathyl-5- phenylpyrazine and excess 2-chlorobenzoyl isocyanate.

8K. 1- (2-bromobenzoyl) -3- (5-trifluoromethyl-2-pyrazinyl) urea, having a melting point of about 206 to 208 ⁰ C, starting from 300 mg of 2-amino-5-trifluormethylpyrazin and 500 mg of 2-BrombenzoyIisocyanat.

8L. 1- (2-chlorobenzoyl) -3- / 5- (4-bromophenyl) -6-chloro-2-pyrazinyl) ■ urea, in a yield of 1.4 g and with a melting point of about 240 to 242 ⁰ C, starting from 0.9 g of 2-amino-5- (4-bromophenyl) -6-chloropyrazine and 0.65 g of 2-chlorobenzoyl isocyanate.

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- Mr-

- * η Qr -

Example 9 1- (2-chlorobenzoyl) -3- / 5- (4-chlorophenyl) -2-pyraziny_l / urea

A solution of 0.5 g of 2-amino-5- (4-chlorophenyl) pyrazine is mixed with 30 ml of dimethylformamide, whereupon the reaction mixture is stirred for about 3 to 4 hours at room temperature. The solution is then poured onto ice, whereupon the precipitate obtained is filtered off and washed with water. The raw material, which weighs 950 mg, is recrystallized twice from a mixture of ethyl acetate and a small amount of dimethylformamide, whereby 200 mg of product which ^{melts at about 231 to 234 °} C. is obtained. According to an elemental analysis and an NMR spectrum ^, this product is 1- (2-chlorobenzoyl) -3- / 5- (4-chlorophenyl) -2-pyraziny ^ / urea.

analysis for C ₁₈ H ₁₆ Cl ₂ N ₄ O ₂ : calculated found C. 55.82% 56.08% H 3.12 3, O7 N 14.47 14.58

Following the general procedure outlined in Example 9 above and using appropriate starting materials, the following additional compounds are prepared, which can be obtained by Elemental analysis and NMR spectra identified:

9A. 1 - (2-chlorobenzoyl) -3 -_ / 6-methyl-5- (alpha, alpha, alphatrifluoro-m-tolyl) -2-pyrazinyl / urea with a melting point of about 202 to 204 ⁰ C in an amount of 0 , 95 g, starting from 1.0 g of 2-amino-5- (alpha, alha, alpha-trifluorom-tolyl) -6-methylpyrazine and 1.3 g of 2-chlorobenzoyl isocyanate.

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- GO-

9B. 1- (2-chlorobenzoyl) -3- / 5- (4-methoxyphenyl) -6-methy1-2-pyrazinyl / urea having a melting point of about 218 g to 221 ⁰ C in an amount of 0.5 starting from 0 , 6 g of 2-amino-5- (4-methoxyphenyl) -6-itiethylpyrazine and 0.95 g of 2-chlorobenzoyl isocyanate.

9C. 1- (2-chlorobenzoyl) -3- / 5- (2,4-xylyl) -2-pyrazinyJL / urea with a melting point of about 218 to 220 g in an amount of 1.06 g, starting from 0.77 g of 2-amino-5- (2,4-xylyl) pyrazine and 1.2 g of 2-chlorobenzoyl isocyanate.

9D. 1- (2-methylbenzoyl) -3- / 6-methyl-5- (alpha, alpha, alphatrifluoro-m-tolyl) -2-pyraziny] L / urea f with a melting point of about 211 to 212 g in an amount of 230 mg, starting of 0.5 g of 2-amino-5- (alpha, alpha, alpha-tifluoro-m-toIyI) -6-methylpyrazine and 0.75 g of 2-mathylbenzoyl isocyanate.

9E. 1- / 5- (4-Methoxyphenyl) -6-methyl-2-pyraziny3 ₁ / -3- (2-methylbenzoyl) urea with a melting point of about 235 to 238 g in an amount of 400 mg, starting from 0.6 g of 2-amino-5- (4-methoxyphenyl) -6-methylpyrazine and 1.0 g of 2-methylbenzoyl isocyanate.

9F. 1- (2-chlorobenzoyl) -3- / 6-methy1-5- (4-methylphenyl) -2-pyrazinyl / urea having a melting point of about 216 g to 217 ⁰ C in an amount of 0.7 starting from 0 , 6 g of 2-amino-6-methy1-5- (4-methylphenyl) pyrazine and 0.8 g of 2-chlorobenzoyl isocyanate.

9G. 1- / 5- (4-bromophenyl) -2-pyrazinyl./-3- (2-chlorobenzoyl) urea having a melting point of about 227 g to 231 ⁰ C in an amount of from 0.7, starting from 0.7 g 2-amino-5- (4-bromophenyl) pyrazine and 1.0g of 2-chlorobenzoyl isocyanate.

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9H. 1- / 5- (4-bromophenyl) -6-ethylr2-pyraziny_l / -3- (2-chlorobenzoyl) urea with a melting point of about 208 to 210 ° (in an amount of 270 mg, starting from 0.6 g of 2-amino-5- (4-bromophenyl) -6-ethylpyrazine and 1.0 g of 2-chlorobenzoyl isocyanate.

91. 1- (2-chlorobenzoyl) -3- / 6-methyl-5- (4-phenoxyphenyl) -2-pyrazinyl / urea having a melting point of from about 204 mg to 207 ⁰ C in an amount of 370, starting from 0 , 5 g of 2-amino-6-methyl-5- (4-phenoxyphenyl) pyrazine and 0.8 g of 2-chlorobenzoyl isocyanate.

9Y. 1- (2-chlorobenzoyl) -3- / 6-methyl-5- (4-biphenylyl) -2-pyrazinyl / urea having a melting point of about 234 g to 237 ⁰ C in an amount of 0.58, starting from 0 , 85 g of 2-amino-6-methyl-5- (4-biphenylyl) pyrazine and 0.7 g of 2-chlorobenzoyl isocyanate.

9K. 1- (2-chlorobenzoyl) -3- / 5- (4-fluorophenyl) -6-methyl-2-pyrazinyl / urea with a melting point of about 211 to

212 ^° C. in an amount of 0.7 g, starting from 0.6 g of 2-amino-5- (4-fluorophenyl) -6-methylpyrazine and 0.6 g of 2-chlorobenzoyl isocyanate.

9L. 1- (2-chlorobenzoyl) -3- / 5- (4-fluorophenyl) -2-pyrazinyl / urea in an amount of 0.2 g with a melting point of about 230-234 ⁰ C, starting from 0.5 g 2-amino-5- (4-fluorophenyl) pyrazine and 0.5 g of 2-chlorobenzoyl isocyanate.

9M. 1- (2-chlorobenzoyl) -3- / 5- (alpha, alpha, alpha-trifluoro-p tolyl) -2-pyrazinyl / urea with a melting point of about

213 to 215 ^° C. in an amount of 0.6 g, starting from 0.6 g of 2-amino-5- (alpha, alpha, alpha-trifluoro-p-tolyl) pyrazine and 0.55 g of 2-chlorobenzoyl isocyanate.

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Example 10

1- / 5- (3-bromophenyl) -6-methyl-2-pyrazinyl _ / - 3- (2-chlorobenzoyl) -

urea

A suspension of 0.7 g of 2-amino-5- (3-bromophenyl) -6-methylpyrazine in 10 ml of dichloroethane is prepared under dry nitrogen, and 0.52 g of 2-chlorobenzoyl isocyanate is added while stirring. A solid precipitate forms immediately. The reaction mixture is stirred for about 30 minutes, after which the solid is filtered off and recrystallized from a mixture of commercially available absolute ethanol and dimethylformamide. In this way, 370 mg of a ^{product which melts at about 201 to 203 °} C. is obtained. Based on an NMR spectrum and an elemental analysis, it is 1- / 5- (3-bromophenyl) -G-methyl ^ -pyrazinyiy-S- (2-chlorobenzoyl) urea.

analysis for C ₁₉ H ₁₅ BrC] LN ₄ O ₂ : calculated found C. 51.20% 51.24% H 3.17 3.44 N 12.57 12.77

Following the general procedure described in Example 10 and using appropriate starting materials the following additional compounds are produced, which are identified by elemental analysis and NMR spectra:

10A. 1- (2-chlorobenzoyl) -3- (5-cyclohexyl-6-methyl-2-pyrazinyl) ■ urea having a melting point of about 203 g to 205 ⁰ C in an amount of from 1.0, starting from 0.6 g Z-amino-S-cyclohexyl-6-methylpyrazine and 0.63 g of 2-chlorobenzoyl isocyanate.

809883/0713

1OB. 1- (2-chlorobenzoyl) -3- / 5- (4-methylthiophenyl) -6-methyl-2-pyrazinyl / urea having a melting point of about 215-216 ⁰ C in an amount of 0.7 g, starting from 0 , 7 g of 2-amino-5- (4-methylthiophenyl) -6-methylpyrazine and 0.6 g of 2-chlorobenzoyl isocyanate.

1OC. 1- (2-chlorobenzoyl) -3- / 6-methyl ~ 5- (2-tolyl) -2-pyrazinyV-urea in an amount of 0.22 g with a melting point of about 206-207 ⁰ C, starting from 0 , 35 g of 2-amino-6-methyl-5- (2-tolyl) pyrazine and 0.4 g of 2-chlorobenzoyl isocyanate.

The compounds of the formula II are suitable for combating insects of various orders, including Coleoptera, like spotted ladybug, cotton boll beetle, corn root beetle larva, Grain leaf beetles, earth fleas, drills, Colorado potato beetles, Grain beetles, alfalfa beetles, carpet beetles, meal beetles, shipyard beetles, wireworms, rice beetles, rose leaf beetles, Plum prick or white larvae of scarab beetles, Diptera, like house fly, yellow fever mosquito, stable fly, horn fly, Blowfly, cabbage fly larva or carrot rust fly, Lepidoptera, such as cotton moth caterpillars, codling moths, owl moth caterpillars, clothes moth, corn meal moth, moth larvae, Corn beetle larva, corn borer, larva of the great cabbage white butterfly, cabbage wrench, larva of the cotton boll beetle, caterpillar of the Bag carrier, eastern tent caterpillar, lawn tensioner or Autumn cotton moth caterpillar, and orthoptera, such as the German cockroach or American cockroach.

It has now been found that the new compounds according to the invention of formula I disrupt the mechanism of metamorphosis occurring in insects, whereby the insects are killed.

809883/0713

It was also found that those compounds of formula II in which

A ^{1 means} bromine or chlorine,

R is hydrogen, trifluoromethyl or

is,

7th
R is hydrogen, chlorine, methyl or trifluoromethyl

represents

R is hydrogen, halogen, methoxy, trifluoromethyl

or is phenyl,

q stands for 0 or 1 and

ρ stands for 0,

ovicid are effective.

The new compounds of the formula II are therefore suitable for combating insects of the genera Coleoptera, Diptera, Lepidoptera or Orthoptera, by treating the habitat of these insects with an insecticidally effective amount of a 1- (monoo-substituted-benzoyl) -3- (substituted-pyrazinyl) urea s of formula II treated.

809883/0713

The method for controlling such insects is carried out in practice so that you have those places where such insects live, treated with an insecticidal composition consisting of an insecticidally effective amount of a Compound of the formula II and a solid or liquid carrier.

To formulate appropriate insecticidal agents from the new compounds of the formula IJ, the respective Active ingredient either mixed with a solid carrier or dissolved or dispersed in a liquid carrier. If so desired Auxiliaries, such as surface-active substances and stabilizers, can also be incorporated into such mixtures.

Such formulations can be aqueous solutions or dispersions, oil solutions and oil dispersions, pastes, Dusts, wettable powders, miscible oils, granulates or aerosols.

The wettable powders, pastes and miscible oils are formulations in concentrated form to be diluted with water before or during use.

To produce corresponding granules, the new active ingredient to be used in each case is taken up in a solvent and then soaks a corresponding granular carrier, for example porous granules, with the solution obtained in this way, such as pumice stone or attapulgite clay, mineral non-porous granules such as sand or ground marl, or organic Granules, it is expedient to use a binder. Such preparations generally contain about 1 to 15%, preferably about 5%, active ingredient.

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- ssr-

- GG-

Mixed to produce appropriate dust formulations the active ingredient in question with an inert solid carrier material in a concentration of, for example, about 1 to 50 percent by weight. Examples of suitable solid support materials are talc, kaolin, diatomaceous earth, dolomite, gypsum, lime, bentonite or attapulgite, and mixtures of these and have similar substances used. Furthermore, organic carrier materials can also be used for this purpose, for example ground walnut shells.

To produce wettable powder formulations, about 10 to 80 parts by weight of a solid inert carrier, for example a carrier of the type indicated above, with about 10 to 80 parts by weight of active ingredient, together with about 1 to 5 Parts by weight of a dispersant such as a lignin sulfonate or an alkyl naphthalene sulfonate, and preferably also with about 0.5 to 5 parts by weight of a wetting agent, for example a fatty alcohol sulfate Alkyl sulfonate or a fatty acid condensate product.

Miscible oil formulations are made by dissolves or suspends the active ingredient in a suitable solvent, which is preferably immiscible with water, after adding an emulsifier. Examples of suitable solvents for this purpose are xylene, toluene and highly aromatic petroleum distillates such as solvent naphtha, distilled tar oil, or mixtures of these materials. as Emulsifiers are suitable for this purpose, for example, alkylphenoxy polyglycol ethers, Polyoxyethylene sorbitan esters of fatty acids or polyoxyethylene sorbitan esters of fatty acids. These miscible oils contain the active ingredient in one concentration from about 2 to 50 percent by weight.

809883/0713

To produce an aerosol preparation, the active ingredient can be used in the customary manner in the form of a solution in a suitable one Incorporate solvent into a volatile liquid suitable as a propellant, for example into a corresponding fluorocarbon.

The formulations which contain an active ingredient of the formula II can of course also contain other pesticidally active substances Connections included. In this way the spectrum of activity of such formulations can be broadened.

The amount of 1- (mono-o-substituted-benzoyl-3- (substituted-pyrazinyl) urea f to be used to control insects in a given area overgrown with plants, of course, depends on a variety of factors, for example extent of surface area of the intensity of infestation by insects, the condition of the treated foliage and the temperature or humidity to be treated vegetative. in general, the application of the active ingredient is recommended in a formulation, the concentration of an active compound of from about O _1, 1 to Contains 1000 ppm.

The insecticidal effectiveness of the new compounds of the formula II can be determined by examining corresponding formulations on caterpillars of the spotted ladybird (Epilachna varivesta) and on caterpillars of the cotton moth (Spodoptera eridania). These insects are representatives of the orders Coleoptera and Lepidoptera. The ones to be examined Compounds are based on multiple tests against these insects at application levels as low as about 1000 ppm 1 ppm has been tested by applying the compounds in these concentrations to the foliage of plants, on which the larvae specified above fed.

809883/0713

- 5Sr-

Attempt 1

The suitability of the new compounds of the formula I as insecticides is determined by the following procedure.

Bean plants are left in about 10 cm square Grow pots that contain 6 to 10 plants per pot. Once the plants are 10 days old, they are ready for the appropriate Investigations used.

Each compound to be tested is formulated by adding 10 mg of active ingredient to 1 ml of solvent (23 g of Toximul R + 13 g Toximul S per 1 of a 1: 1 mixture of anhydrous ethanol and acetone) and then the whole thing with 9 ml of water mixed. In this way, active ingredient solutions are also obtained an active ingredient concentration of 1000 parts per million (ppm). (Toximul R and Toximul · S are surface-active Mixtures of sulfonates and nonionics, and these products are made by Stepan Chemical Company, Northfield, Illinois.) A portion of a test solution diluted with an active ingredient concentration of 1000 ppm then in a ratio of 1:10 with the specified solvent · that a test solution with a concentration of active ingredient of 100 ppm. The solutions of the compounds to be investigated are sprayed with the respective concentration of active ingredient then on the bean plants in the individual pots. The plants are then left to dry and removed 12 leaves and wrapped around the stalks with water-soaked cellulose. The leaves are then on a total of 6 Petri sharks made of plastic, which are 100 χ 20 mm in size. In each 2 Petri dishes are then placed 5 larvae of spotted ladybirds from the second manifestation (Epilachna varivestis) and 5 larvae of the cotton moth caterpillar from the second

809883/0713

and the third manifestation. Subsequently, to set the individual petri dishes for about 4 days in a climate room at a temperature of about 25.5 ⁰ C and a relative humidity of about 51%. The first results of the action of the compounds to be investigated are then determined. Subsequently, two fresh larvae from the originally treated pots are placed in each Petri dish. The individual dishes are then placed in a climatic room with the temperature and humidity conditions specified above for a further 3 days, whereupon the appropriate assessment is made at the end of the seventh day. The percent control of the insects is determined by determining the number of living larvae per Petri dish. All treatments are compared to solvent controls and untreated controls. The test results are evaluated according to the following rating scale (percentage control):

0 = 0% control

1 = 1-50% control

2 = 51-99% control

3 = 100% control

The results obtained in the above tests are shown in Table I below. In column 1 of this table the compounds used are indicated by the number of their preparation example, while column 2 shows the amounts used for the active ingredient in parts per million (ppm) and in columns 3 to 6 the assessment values after 4 days and after 7 days for the two insects mentioned there for the different concentrations of active substances, namely for the application quantities of 1000 ppm and 100 ppm.

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Table I Rating Values
Order- spotted ma- caterpillar of the tree-

lot rxenkafer 7th day 4th 3 wool moth Connect 3 3 manure ppm 4th day 2 2 Day 7th day 8th 1000 1 2 1 3 100 1 1 1 3 8A 1000 1 0 0 2 100 1 0 3 1 SB 1000 0 ■ 3 3 2 100 0 2 3 1 8C 1000 0 1 3 3 100 0 0 3 3 8D 1000 0 2 3 3 100 0 3 2 3 8E 1000 0 2 0 3 100 0 1 2 3 8F 1000 1 3 0 2 100 0 2 1 0 8G 1000 0 0 0 2 100 0 0 3 0 8H 1000 0 2 3 0 100 0 1 3 0 81 1000 0 1 2 3 100 0 0 2 3 8Y 1000 0 2 2 3 100 Q 2 2 8K IQOO 2 2 100 2 2

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T a at: 7th day Caterpillar of tree
wo1! moth 7th day ■ W-
le ii 2 4th day 3 assignment
lot (Continuation) 0 3 3 Connect
manure PPm Assessment values 0 3 3 8L 1000 spotted ma
shark beetle 0 3 3 100 4th day 3 3 3 9 1000 0 2 2 3 100 0 0 2 1 9B 1000 0 0 1 0 100 0 2 C. 3 9C 1000 2 1 3 3 100 1 1 3 3 9D 1000 0 0 3 3 100 0 3 2 3 9E 1000 1 3 2 2 100 0 0 2 3 9F 1000 0 0 3 3 100 0 0 2 3 9G 1000 2 0 2 1 100 2 2 0 2 9H 1000 0 2 2 1 100 0 1 1 3 91 1000 0 0 3 1 100 0 0 9Y 1000. 2 100 1 0 0

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Table I (port setting) assessment values

Order- spotted Ma- caterpillar of the tree crowd beetle V7ol! Moth

Connect
manure ppm 4th day 7th day 4th day 7th day 10 1000 0 3 3 3 100 0 1 2 2 1OA 1000 1 3 3 3 100 0 2 3 3 1OB 1000 1 3 2 3 100 0 1 0 2

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Attempt 2

Several of the new compounds of the formula II investigated in Experiment 1 are re-examined, but with lower Application amounts is worked. The bean plants used for this purpose are prepared in the same way as in Experiment 1. The too investigating compounds are formulated as follows:

10 mg of the respective active ingredient are dissolved in 1 ml of solvent dissolved, whereupon the whole thing is diluted with 9 ml of water, so that a solution with an active ingredient content of 1000 ppm results.

By diluting this solution in series, solutions are then formed which contain the active substance concentrations required for the experiments contain.

A 50:50 mixture of alcohol and acetone is used as the solvent used, which contains 23 g Toximul R and 13g Toximul S per liter.

The percentage control is determined by counting the number of living larvae of caterpillars of the cotton moth (Spodoptera eridania) counts per Petri dish and then uses the values obtained using the Abbott / W formula. W. Abott, "A. Method of Computing the Effectiveness of an Insecticide ", J. Econ. Entomol. 18, 265-267 (1925] _ / as follows the percentage Control determined:

Number of animals surviving in the control

- Number of surviving animals in the percentage of treated Petri dishes

Control Number of surviving animals in the control

The results obtained with the above differences are assumed Table II below. Test results based on more than one test are indicated by mean values.

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Table II

assignment percentage control Cotton moth lot Caterpillar of: 7th day link in ppm 4th day 100 8th 100 100 100 50 100 100 25th 100 100 10 95 96 5 57 93 2.5 54 76 1.0 17th 20th 0.5 0 100 8C 100 ■ 100 100 50 100 100 25th 100 100 10 100 100 5 100 100 2.5 100 93 1.0 60 73 0.5 20th 100 8D 100 100 100 50 100 100 25th 100 100 10 100 100 5 100 100 2.5 100 67 1.0 33 27 0.5 7th

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28268S3

Tabel II (continued)

assignment percentage control / 0713 Bumwollinotte lot Caterpillar of the '. 7th day link in ppm 4th day 100 3E 100 100 100 50 100 100 25th 100 93 10 81 100 5 80 47 2.5 27 100 81 100 100 100 50 100 100 25th 100 100 10 100 100 5 96 100 2.5 80 73 1.0 20th 53 0.5 0 100 8L 10 100 75 5 13th 100 9 100 100 100 50 93 100 25th 93 100 10 57 76 5 30th 27 2.5 13th 0 1.0 0 7th 0.5 7th 809883

T a b e lie II 2826893
(Continuation) Cotton moth assignment percentage control 7th day lot Caterpillar of 100 link in ppm 4th day 100 9A 100 100 100 50 100 100 25th 100 100 10 100 100 5 100 80 2.5 93 40 1.0 20th 100 0.5 23 100 9B 100 93 93 50 100 73 25th 86 100 10 27 100 9D 100 100 100 50 100 100 25th 100 100 10 100 100 5 100 100 2.5 100 100 1.0 53 100 9E 100 100 100 50 100 100 25th 100 73 10 86 5 27

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T a b e - & Γ-
1 1 e II 2826893
(Continuation) Cotton moth assignment percentage control 7th day lot Caterpillar of 47 link in ppm 4th day 27 2.5 27 100 1.0 20th 93 9F 100 100 100 50 87 93 25th 93 100 10 67 100 9G 100 100 10ü 50 93 100 25th 100 100 10 80 73 9K 10 100 100 5 20th 27 1OA 10 67 5 0

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Attempt 3

One of the compounds falling under general formula II was also found against larvae of the Egyptian cotton leaf moth (Spodoptera littoralis) examined.

For this purpose, the compound to be investigated is dissolved in acetone and the resulting solution is diluted with water, which contains a surfactant ..

The compound formulated in this way is then used to spray cauliflower plants in a field. In connection, it is used to remove leaves from the plants and feed them to larvae that are in the laboratory and collected from the field the Egyptian trefoil moth from the first to third Manifestation. The amounts obtained after the 4th day of the experiment and after the 7th day of the experiment with the specified order quantities percentage mortality values are given in the table below. The connection used is by number of their production example.

Tabel

III

Percent mortality

Larvae of the Egyptian

Cotton leaf moth

assignment
lot from the
2. Appearance 7th day link in ppm 4th day 100 8th 100 90 100 75 80 100 50 90 100 25th 70

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After determining the test values obtained after the 7th day one takes more leaves from the cauliflower plants in the field and determines the remaining activity of these leaves in the manner already described above after the 4th day of the experiment and the 7th day of the experiment. The results obtained here are shown in Table IV below.

Tabel

IV

link
8th

Percent mortality.

Larvae of the Egyptian

Cotton leaf moth

assignment
lot from the
2. Appearance 7th day in ppm 4th day 100 100 40 100 75 80 100 50 40 8C 25th 0

Attempt 4

The aim of this experiment is to determine the local systemic effectiveness of several compounds of the formula II.

The compounds to be examined are each 50 percent formulated wettable powders. Each formulation is diluted with water to give the desired concentration of the compound to be investigated.

Soybean seeds (variety Calland) are sown and allowed to germinate. 7 days after sowing, when the cotyledons have developed, you spray the soybean plants until they run off with the Test solutions and then put the plants again for 1 week

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into the greenhouse. At the end of this week, the plants are harvested and cut open, whereby the cotyledons (viz separates the sprayed leaves) from the newly grown parts or the three-part leaves (new leaves) that are separated developed within 7 days of spraying.

The sprayed leaves are placed in Petri dishes containing larvae of the caterpillar of the cotton moth from the second and third instar (Spodoptera eridania), and the new leaves are placed in separate Petri dishes which also contain larvae from the second and third instar of the caterpillar of the cotton moth . Then there is the individual petri dishes in a climate-controlled room with a temperature of about 25.5 ⁰ C and a relative humidity of about 51%.

After four days the larvae are observed to determine the influence of the to determine compounds to be examined. After this assessment, the surviving larvae are transferred from the treated ones Larvae or from the new larvae in clean Petri dishes containing untreated soybean leaves. The petri dishes are then placed in the climatic room for a further three days until the final assessment is carried out after the 7th day.

Percent control values are the same as described in Experiment 2 above, using the same Formula determined. The results obtained are shown in Table V below.

In this table, in column 1, the compounds used are indicated by the number of their preparation example, while Column 2 shows the order quantity in parts per million (ppm), columns 3 and 4 show the values for the percentage Control on the sprayed or on the new leaf value after the 4th day of the experiment are indicated and in columns 5 and 6 the Values for the percentage control for sprayed or new leaf value after the 7th day of the test are given.

809883/0713

Tabel

assignment percentage Combat 7th day New lot Caterpillar the cotton moth sprayed 100 in ppm 4 »day 100 94 link 1000 sprayed New 100 28 8th 100 100 73 88 94 10 100 22nd 100 89 1000 29 0 100 22nd 8C 100 100 94 100 100 10 100 55 100 83 1000 47 0 100 22nd SD 100 100 78 88 10 Ϊ00 17th 23 0

The above results show that with soybeans there is a
Transfer of the insecticidally active compounds comes.

Attempt 5

Several compounds of Formula II according to the invention are also used examined for their effectiveness as insecticides against yellow fever mosquito (Aedes aegypti) of the order Diptera.

To formulate each active ingredient, 10 mg of the compound to be examined is dissolved in 1 ml of acetone and mixed
this solution then with 99 ml of water, so that a test solution with an active ingredient concentration of 100 ppm results.
This solution with an active ingredient concentration of 100 ppm is then used to form the required test solutions with lower active ingredient concentrations by serial dilution with water. In each case 40 ml of the test solutions obtained in this way are given

809883/0713

then either in 100 ml glass beakers or in 160 ml plastic container, whereby one per active ingredient concentration two cups or containers are used at a time. Twenty 24-hour-old mosquito larvae are then placed in each container from the 3rd manifestation. The larvae are fed as a whole With 10 to 20 mg of Purina powdered laboratory food daily for 7 days. The containers are left in place during this time in a climatic room as used in experiment 1. After the 7th day of the experiment, the percentage mortality values are determined for the mosquito larvae by removing the live larvae counts. All treatments are compared to solvent controls and untreated controls. The Results are shown in Table V below.

In this table, in column 1, the compounds used are identified by the number of their preparation example, while column 2 shows the amount applied in ppm and column 3 shows the values for percentage mortality the specified order quantities are specified.

Table VI

Killing of yellow fever mosquito larvae * link Application amount in ppm percent mortality 8th 0.01 1OO 8C 0.01 1OO 81 0.01 100 solvent - 0 untreated __ 0

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Trial 6

This experiment determines the ovicidal effectiveness of several compounds of the formula II, using egg grapes the caterpillar of the cotton moth (Spodoptera eridania) and the spotted Ladybird (Epilachna varvestis) used.

The egg grapes, which are on bean leaves of the Bountiful variety, are placed on a paper towel and ^{sprayed with the active ingredient solutions under low air pressure (about 0.21 × 10 dynes / cm 2} ) using a DeVilbiss atomizer. The active ingredient solutions used for this purpose are prepared as described in Experiment 1. After spraying, the eggs are dabbed off with a paper towel and placed in appropriate plastic Petri dishes (60 χ 15 mm) together with a piece of a moist tooth tampon. The egg grapes in the Petri dishes are then incubated until the untreated controls have hatched. At this point the number of eggs that hatched is determined. The test results obtained in this way are determined in the form of percentage values compared to the percentage values of the controls. They are shown in Table VII below.

In column 1 of this table, the compounds used are identified by the number of their preparation example, while column 2 shows the amount applied in parts per million (ppm) and column 3 gives the values for the percentage destruction.

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TJ "- -

Tabel

VII

on
wear Percentage kill
Killing the eggs link lot
in ppm Cotton Mary
moth beetle 8th 1000 100 500 100 250 100 100 100 50 100 8C 1000 100 500 100 250 100 100 100 8F 1000 100 8G 1000 100 81 1000 100 500 10 0 250 100 100 100 3Y 1000 100 8K 1000 100 500 100 250 100 100 100 50 100 9A 1000 100 500 100 250 100. 100 100 50 ₁₀₀ 809883 / C!

13th

Tabel

VII

(Continuation) Percentage kill
Killing the eggs Marien
Beetle on
wear Cotton
moth link lot
in ppm 100 9B 1000 100 500 95 250 100 100 100 100 9Y 1000 100 96 9K 1000 100 96 500 100 2 50 100 100 100 50 100 25th 96 10 100 5 100 10 1000

The test results show that the formula II
falling new compounds are effective against a
Series of insects in the larval state, as the insects ingest the foliage or other parts of their environment, such as water or manure, that have been treated with active ingredient. The new compounds of the formula II are also suitable as ovicides.

803883/0713

Claims (32)

Claims Z826893 Process for the preparation of 1- (mono-o-substituted-benzoyl) -3- (substituted-pyrazinyl) ureas of formula I. OHOH II I II I - C - M - C - N - R (I) N ₃ Ä Chlorine, fluorine, bromine, methyl or trifluoromethyl means, B hydrogen, chlorine, fluorine, bromine, methyl or tri- is fluoromethyl, R for / V VV VV ^ - (x). or η "V stands, «098Ö3 / 0713 -Z- R hydrogen, halogen, Cj-Cg-alkyl, halogen (C.-C ₄ - alkyl), cyano, * - · \ - (CH) S "y · - or means, R is hydrogen, halogen, methyl, ethyl, cyano or Is halo (C ₁ -C ₄ ) alkyl, 3 4
R and R are identical or different and are hydrogen, Halogen, C.-C -.-ALky !, cyano, or halo (C.-C.) alkyl mean, R for halogen, halogen (C ₁ -C ₄ ) alkyl, Cj-Cg-alkyl, Is cyano or phenyl, X is halogen or C ₁ -C ₄ -Al ^ yI, Y is halogen, Z represents oxygen or sulfur, η stands for 0, 1 or 2, ρ stands for 0 or 1 and m is 0, 1, 2 or 3. 809883/0713 characterized in that between the residues -C- and. -R in which A, B and R have the meanings given above, building a ureido bridge / by either (a) a benzamide of the formula / 0 with a C ₁ -C ₇ -AIkYlUtMUm and a phenyl chloroformate in an inert solvent at about -80 to -40 ⁰ C to form a urethane as an intermediate, this intermediate with an amine of the formula R-NH ₂ is reacted in an inert solvent at about -80 to -40 ⁰ C and the reaction mixture is then slowly warmed to form the desired benzoylurea and heated to about 50 to 100 ⁰ C, or (b) a benzamide of the formula ^ 0 with a Cj-C_-Alkyllithium in an inert solvent at about -80 to -40 ⁰ C with formation of the corresponding 809883/0713 ~ * - 282S893 Lithium salt and then reacting brings this lithium salt with a carbamate of an amine of formula RNH "and a phenyl chloroformate to the reaction to give this treatment in an inert solvent at about -80 to -40 ⁰ C with subsequent slower increasing the temperature to about 20 to 40 ⁰ C carries out to form the desired benzoylurea. 2. The method according to claim 1, characterized that you can see the ureido bridge between the remains / 0 / \ —C-NHa and, NHa-R, ^x ~ <■ '■ wherein A, B and R are as defined in claim 1, by the process of step (a). 3. The method according to claim 1, characterized that you can see the ureido bridge between the remains / 0 Il and NHa-R, wherein A, B and R are as defined in claim 1, by the process of step (b). 809883/0713 4. The method according to claim 1, characterized that one uses compounds in which the substituent B has a meaning other than hydrogen Has. 5. The method according to claim 1, characterized that one uses compounds in which the substituent R for • ι ο is, where the substituents R and R to claim have given meanings. 6. The method according to claim 1, characterized that one uses a compound in which the substituent R for ^Kj n stands, where X and η have the meanings given in claim 1. 7. The method according to claim 2, characterized in that the first part of the reaction is carried out at a temperature of about -75 to about -65 ⁰ C and the second part of the reaction at a temperature of about 50 to about 65 ⁰ C is carried out. 809883/0713 8. The method according to claim 1, characterized that n-butyllithium is used as the alkyllithium. 9. The method according to claim 1, characterized that a compound is used in which A and B are each chlorine. 10. 1 - (Mono-o-substituted-benzoyl) -3- (substituted-pyrazinyl) ureas of formula II / 'ο ο / V A ^{1 is} bromine, chlorine or methyl, Halogen, C-j-Cg, Nitro, Cyano, R hydrogen, halogen, C-j-Cg cycloalkyl, halogen (CH ₂ ) - · ( K ' -X -. ( K or is naphthyl, R is hydrogen, halogen, methyl, ethyl, cyano or Represents halogen (C ₁ -C ₂ ) alkyl, 6 7 with the proviso that the substituents R and R cannot be hydrogen at the same time, 809883/0713 - -Pf- R hydrogen, halogen, halogen (C ₁ -C ₄ ) alkyl, C.-C.-alkyl, C _Λ -C. -Alkoxy, C.-C.-alkylthio, It) I 4 I. C.-C -.- alkylsulfinyl, C ..- ^ - alkylsulfonyl, Means nitro, cyano, phenoxy or phenyl, q is 0, 1, 2 or 3, ρ stands for 0 or 1 and X ¹ for 0 0 11 it -Ο-, -S-, -S- or -S- Il 0 stands. 11. 1- (mono-o-substituted-benzoyl) -3- (substituted-pyrazinyl) ureas according to claim 10, characterized in that A ¹ , q, ρ and X 'have the meanings given in claim 10, R hydrogen, halogen, C ^ Cg cycloalkyl, halogen (C ₁ -C ₄ ) alkyl, or is naphthyl, represents hydrogen, halogi -C ₂ ) alkyl, the proviso that di <cannot be hydrogen at the same time, and 809883/0713 R hydrogen, halogen, methyl, ethyl or halogen with the proviso that the substituents R and R - Kr R halogen, halogen (C ..- C.) Alkyl, C.-C _g -alkyl, C ₁ Alkoxy, Cj-C ^ -alkylthio, Cj-C ^ alkylsulfinyl, Means alkylsulfonyl, nitro or cyano. 12. 1- (Mono-o-substituted-benzoyl) -3- (substituted-pyra- zinyl) ureas according to claim 10, characterized in that A ¹ , q and ρ have the meanings given in claim, R halogen, halogen (C ₁ -C ₃ ) alkyl, C ₃ -Cg -cycloalkyl, - (CH) -f ^. or -χ, - ^2P \ / means, R is hydrogen, halogen, halogen (C ₁ -C ₂ ) alkyl or Represents methyl, R hydrogen, halogen, halogen (C ₁ -C ₃ ) alkyl, or C ₁ -C ₃ alkoxy and X ^{1 is} -0- or -S-. 13. 1- (Mono-o-substituted-benzoyl) -3- (substituted-pyra- zinyl) ureas according to claim 10, characterized , that A ^{1 is} bromine, chlorine or methyl, 809883/0713 ' R ⁶ for · \ _Β / · or cyclohexyl stands, R halogen, halogen (Cj-C ₃ ) alkyl, C ₁ -C ₂ -alkyl or Is C ₁ -Cp-alkoxy, ρ stands for 0, g stands for 1 or 2 and R is hydrogen or methyl, with the proviso that the substituent R is chlorine or bromine in • 7
Must be p-position if R is hydrogen and q is 1. 14. 1- (2-Chlorobenzoyl) -3- / 5- (4-bromophenyl) -6-methyl-2-pyrazinyl / urea according to claim 10. 15. Ί- (2-bromobenzoyl) -3- / 5- (4-bromophenyl) -6-methyl-2-pyraziny 3./urea according to claim 10. 16. 1- (2-chlorobenzoyl) -3- / 5- (4-chlorophenyl) -6-methyl-2-pyrazinyl / urea according to claim 1Q. 809883/0713 17. 1 - (2-chlorobenzoyl) -3- / 5- (4-chlorophenyl-2-pyraziny_l / urea according to claim 10. 18. 1- (2-chlorobenzoyl) -3- / 6-methy1-5- (alpha, alpha, alpha-trifluoro-m-tolyl) -2-pyrazinyl / urea according to claim 10. 19. 1- (2-Methylbenzoyl) -3- / 5- (4-bromophenyl) -6-methyl-2-pyrazinyl) _ / urea according to claim 10 » 20. 1- (2-chlorobenzoyl) -3- / 5- (4-ethylphenyl) -6-methyl-2-pyrazinyl / urea according to claim 1O. 21. 1- (2-chlorobenzoyl) -3- / 5- (4-methoxyphenyl) -6-methyl-2-pyrazinyl / urea according to claim 10. 22. 1- (2-Methylbenzoyl) -3- / 5- (alpha, alpha, alpha-trifluorom-tolyl) -6 ~ methyl-2-pyrazinyl / urea according to claim 10. 23. 1- (2-chlorobenzoyl) -3- (5-cyclohexyl-6-methyl-2-pyrazinyl) urea according to claim 10. 24. 1- (2-Chlorobenzoyl) -3- / 5- (4-methylthiophenyl) -6-methyl-2-pyrazinyl / urea according to claim 10. 25. 1- (2-Chlorobenzoyl) -3- / 5- (4-fluorophenyl) -6-methyl-2-pyrazinyl ^ / urea according to claim 10. 809883/0713 26. Process for the preparation of 1- (mono-o-substituted benzoyl) -3- (substituted-pyrazinyl) ureas of formula II A ^{1 is} bromine, chlorine or methyl, R hydrogen, halogen, Cg-Cg-cycloalkyl, halogen (C ₁ -C.) Alkyl, nitro, cyano, or is naphthyl, R is hydrogen, halogen, methyl, ethyl, cyano or Represents halogen (C ₁ -C ₂ ) alkyl, with the proviso that the substituents R and R cannot be hydrogen at the same time, R hydrogen, halogen, halogen (C ^ C ₄ ) alkyl, C | -C ₆ -alkyl, C ₁ -C ₄ -AIkOXy, Cj- ^ C ₁ -C ₄ -alkylsulphinyl, C ..- C ₄ -alkylsulphonyl, nitro, cyano, phenoxy or phenyl, stands for 0, 1, 2 or 3, 809883/0713 -42- ρ stands for O or 1 and X ¹ for 0 0 Il Il -0-, -S-, -S- or -S- 0 stands, characterized in that one between compounds of the formulas / \ —CR ^e and 9 1C
wherein R and R are amino or isocyanate, first forms a ureido bridge and the compounds possibly obtained ^{thereafter in which X 1 is} -S-, then oxidized, if one would like to have compounds of the formula II in which X ^{1 is} 0 0 Il Il -S- or -S- 0
stands. 27. Insecticidal agent composed of an active ingredient and a suitable carrier, characterized in that that it contains a compound according to claim 10 as active ingredient. 809883/0713 28. Insecticidal agent according to claim 27 _r, characterized in that it contains about 1 to 15 percent by weight of active ingredient and is in granular form. 29. Insecticidal agent according to claim 27, characterized in that it is about 1 to 50 percent by weight Contains active ingredient and is in the form of dust. 30. Insecticidal agent according to claim 27, characterized in that it is about 2 to 50 percent by weight Contains active ingredient and is in the form of a miscible oil with a suitable emulsifying agent. 31. Insecticidal agent according to claim 27, characterized in that it contains about 10 to 80 parts by weight of active ingredient and in the form of a wettable powder with an inert carrier, a dispersant and a wetting agent. 32. Method of combating insects, thereby marked that one has appropriate plants with a compound of the formula II wherein A ¹ , R and R have the meanings given in claim 10 , treated. 303883/0713