DD141831A5 - PROCESS FOR PREPARING 1- (MONO-O-SUBSTITUTED-BENZOYL) -3- (SUBSTITUTED-PYRAZINYL) -HARNSTRATES - Google Patents

Abstract

A process for the preparation of 1- (mono-o-substituted-benzoyl) -3- (substituted-pyrazinyl) ureas by the treatment of a benzamide with a C 1 -C 3 alkyllithium and a phenyl chloroformate in an inert solvent at -80 to -40 oc to form an intermediate intermediate, which is reacted with an amine of the formula R-NH 2 in an inert solvent at -8 0 to 40 0C and heated to 50 to 100 0C to form the benzoylurea, or that a benzamide with a Cj-C7 alkyl] lithium in an inert solvent to give the corresponding lithium salt which reacts with the carbamate of an amine and a phenyl chloroformate, in an inert solvent at -80 to -40, C and then heating to 20 to 40 0C is converted to Eenzoyiharnstoff.

Description

Application area of. Invention ·

The control of insects is of vital importance in today's ever-increasing world population. Insects, such as those belonging to the genera Lepidoptera, Coleoptera, Diptera, Homoptera, Hemiptera and Orthoptera, cause known in the state of larvae great damage to crops, for example, serving as food crops and fibrous crops. Control of such insects is important to the well-being of humankind, as it increases the yield of food crops and fibrous crops used, for example, to make clothing.

Chaiakteiistik the known technical solutions in US-PS 3,748,356 a number of substituted benzoyl ureas is already described, which are to be highly insecticidal effect , with these compounds, it is generally 1- (2,6-dichlorobenzoyl) -3- (substituted -phenyl) ureas, with this

however, further include several 1- (2,6-dichlorobenzoyl) -3- (substituted-pyridyl) ureas. There are already a number of methods for preparing such compounds, but the steps of the present method are not used.

From US-PS 3,989,842 insecticidal agents and methods for controlling insects in agriculture and horticulture emerge, where as active ingredients certain N- (2,6-dihalobenzyl) -N ¹ - (substituted-phenyl) ureas and several N - (2,6-dichlorobenzoyl) -N '- (substituted pyridyl) ureas.

U.S. Patent 3,933,908 discloses other N- (2,6-dihalobenzoyl) -N ¹ - (substituted-phenyl) ureas which are also said to be insecticidal. ·

The insecticidal activity of 1- (2,6-dichlorobenzoyl) -3- (3,4-dichlorophenyl) urea is discussed in a number of references. In detail, this is the science 59, 312-313 (1972); ibid. 60, 431-432 (1973) and Pestic. Be. 4, 737-745 (1973).

In J. Med. Ent. 10, 452-455 (1973) and J. Econ. Ent. 67, 300-301 (1974) reports studies on the inhibition of the formation of mosquitoes and house flies as well as on the control of lucerne beetle by 1- (4-chlorophenyl) -3- (2,6-difluorobenzoyl) urea.

US Pat. No. 3,992,553 discloses mono-o-chloro-substituted-benzoylureidodiphenyl ethers which are to be excellently insecticidal with respect to plant pests and which are also intended to represent ectoparasiticides in veterinary medicine.

From BE-PS 833 288 are insecticidally effective disubstituted

j '

Benzoylpyrazinylureas known. However, the process described therein for preparing these compounds differs from the present production process.

In BE-PS 838 286 1-benzoyl-3 ~ (4-phenoxyphenyl) ureas are described which are to be insecticidally effective and have only a low mammal toxicity and plant toxicity.

OBJECT OF THE INVENTION The invention is now directed to a new process for the preparation of 'benzoylureas, and the compounds are hereafter available insecticides.

Explanation of the essence of the invention .

There has now been found a process for the preparation of benzoylureas, as described, for example, in US Pat. No. 3,748,356 and BE Pat. No. 833,288, which consists therein. that a benzamide, a Cj-C ^ -Alkyllithium, a phenyl chloroformate and an amine is reacted together. 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 to -40 ⁰ C and then the temperature to form the desired Benzoy! urea then slowly increased to about 50 to 100 ⁰ C. A second embodiment of the present method is that it treats the C benzamide with an alkyl lithium in an inert solvent at about -80 to -40 ^0, the lithium salt thus obtained then with a carbamate at a temperature of about -80 to -40 ⁰ C reacts and the mixture finally comes to about 20 to 40 ⁰ C to form the desired Benzoylharnstoffs. The carbamate needed for this purpose is formed by reacting an amine with a phenyl chloroformate.

The inventive method for the preparation of 1- (monoo-substituted-benzoyl) -3- (substituted-pyrazinyl) ureas of the formula I.

Z ¹ OHOH

^ - C-N - C-N-R (I)

A is chlorine, fluorine, bromine, methyl or. Trxfluormethyl

means

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

fluoromethyl is ,.

- R for

/ V

e β \ ^. _λ or

β. Λ

stands,

206203

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

alkyl), cyano,.

^vx'm

means

2 *

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

Is halogen (C ₁ -C.) Alkyl,

34 R and R are the same or different and are hydrogen,

Halogen, C 1 -C ₆ -alkyl, cyano or halogeno (C 1 -C ₄ ) -alkyl,

R ^{5 is} halogen, HaloC ₁ C ₁ -C ₄ alkyl, C ₁ -Cg alkyl,

Cyano or phenyl,

X is halogen, Y or C, -C alkyl,

Y is halogen,

f) Z represents oxygen or sulfur,

η is 0, 1 or 2,

ρ is 0 or 1 and

m is 0, 1, 2 or 3,

is characterized in that one between the residues

AO

¹ I and

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

(a) a benzamide of the formula

_ / 0 / " VS-NH

with a C.-C 1-4 -alkyllithium. and reacting a phenyl chloroformate in an inert solvent at about -80 to -40 ⁰ C to form a urethane intermediate, this intermediate with an amine of formula

R-NH ₂

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

(b) a benzamide of the formula

/ 0

with a C.-C ^ -alkyllithium. in an inert solvent at about -80 to -40. ⁰ C to form the corresponding

Reacting this lithium salt and then this lithium salt with a carbamate of an amine of formula RNH "and a Phenylchiorformiat to the reaction, wherein this treatment in an inert solvent at about -80 to -40 ⁰ C with subsequent slow increase in temperature to about 20 to 40 ^{Performs 0} C 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 meaning other than hydrogen. Very particular preference is given to those compounds in which A and B are chlorine.

In the above description, the individual terms have the usual meanings in chemistry. The alkyl groups may be straight-chain or branched-chain. By halogen is meant fluorine, chlorine, bromine or iodine. ,

According to step (a) of the present process, the hexylation of compounds of the formula I is carried out according to the following reaction scheme:

> -C-NH

0 * ι '' - C

RNH ₂

^ E-C-NH-C-O-®:

.V

♦ C

For the above reaction, the benzamide used in step 1 and. the Amiη used in step 2 so that the gewünsci te benzoylurea results. Preference is given to benzamides in which

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

The first step of the process preferably uses a phenyl chloroformate, and more preferably 4'-nitrophenyl chloroformate. However, it is also possible to work with other phenyl chloroformates, such as 2,4-dinitrophenyl chloroformate or 4-trifluoromethylphenyl chloroformate. The first stage of the process 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 carried out at about -80 to about -40 ⁰ C, preferably about -75 to about -65 ⁰ C.

As the alkyl lithium compound, any alkyl lithium containing 1 to 7 carbon atoms can be used. n-Butyllithium is preferred as Alkyllithium.

In the above Verfahren.zur carrying out the present reaction at the stage, are (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 respective solvent and The resulting mixture then stirred for about 30 minutes at this low temperature. Subsequently, the phenyl chloroformate dissolved in the respective solvent is added at this low temperature over a period of about 15 to 20 minutes, and the resulting mixture is then stirred in the cold for about 2 to about 6 hours.

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

20 6 203

the first stage obtained urethane. 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 method for carrying out the reaction according to the above process step (b), the reaction mixture is combined in a different order. As a first step, the benzamide is treated with a C ..- C ₇ --Alkyilithiuiu in an inert solvent at a temperature of -80 to -40 ⁰ C to form the corresponding lithium salt. This stage is carried out in the same way as the first stage of the first embodiment of the present method, namely the "" stage (a). Again, n-butyllithium is preferably used as the alkyl lithium. The Lithiurnsalz thereby 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 the formula RNH-. The reaction mixture is then stirred for about 0/5 to 6 hours at low temperature, after which the mixture is allowed to warm to a temperature of about 20 to 40 ⁰ C to form the desired benzoylurea and this temperature is maintained for about 1 to 24 hours. Suitable solvents for this process step are tetrahydrofuran, diethyl ether or toluene.

The invention further relates to novel 1- (mono-o-substituted-benzoyl) -3- (substituted-pyrazinyl) ureas of the formula II .

__ Λ 0 0 f \ /

S > C - N - C - N - λ ^] 1

\ / ι ι \ / V

HH

worm

206203

A 'is bromine, chlorine or methyl,

R is hydrogen, halogen, C_-C ^ cycloalkyl, halogen

(C ₁ -C ₄ ) alkyl, nitro, cyano,

se ^q

or 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 can not simultaneously be hydrogen,

S

R is hydrogen, halogen, halogen (C.-C ₄ ) alkyl,

C ₁ -C ₆ -alkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -alkylthio,

_N _ Cj-C ^ alkylsulfinyl, _C1 ^ alkylsulfonyl,

^Λ nitro, cyano, phenoxy or phenyl,

g is 0, 1, 2 or 3,

ρ is Ο or 1 and

X ¹ for

  ο o

Il

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

stands.

20 6 203

The preparation of these compounds of formula II is carried out by reacting the compounds of the formulas

  / 'O β - β

/ -C-, and R -W -V,

9 10

worm R and R ammo or isocyanate, first forming an ureido bridge and then possibly obtained compounds in which X 'is -S-, then oxidized, if one wants to have compounds of formula II in which X ¹ for

0 0

Ii. ii

-S or -S-

Il

  ο

stands.

Preference is given to those compounds of the above formula II in which

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

R is hydrogen, halogen, C 1 -C 4 -cycloalkyl, halogen

or naphthyl,

R is hydrogen, halogen, methyl, ethyl or halogen

Represents (C ₁ -C ₂ ) alkyl,

with the proviso that the substituents R and R can not simultaneously be hydrogen,

R is halogen, halo (C ₁ -C ₄ ) alkyl, C ₁ -C ₆ -alkyl, C ₁ -C ₄

Alkoxy, C ₁ -C ₄ -AlkYItMo, C ₁ -C ₄

Alkylsulfonyl, nitro or cyano,

q is 0, 1, 2 or 3,

ρ is 0 or 1 and

X ¹ for

0 0

Il

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

Il

stands.

More preferred are those compounds of formula II above in which

A ¹ . Bromine, chlorine or methyl,

R is halogen, halogen (C ₁ -C ₃ ) -alkyl, C 1 -C -cycloalkyl,

means

R is hydrogen, halogen,. Halogen (C ₁ -C ₂ ) alkyl or

Represents methyl,

R is hydrogen, halogen, halogen (C.-C ") alkyl,

or C ₁ -C ₃ -alkoxy, q is 0, 1 or 2,

ρ is 0 or 1 and

X ^{1 stands} for -0- or -S- "

Most preferred are those compounds of formula II above in which

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

R ⁶ for

₂ )

* x ^q

y » - odeif cyclohexyl

, R halogen, halo (C ₁ -CJ alkyl, C ₁ -C ₀ -alkyl or

₁₃ means is 0, is 1 or 2 and

R is hydrogen or methyl,

with the proviso that the substituent R is chlorine or bromine in

p-Stel

stands.

p position must, if R is hydrogen and q for

Halogen is understood in the above formula II fluorine, chlorine and bromine.

The term C 1 -C 10 -cycloalkyl refers to cycloalkyl having 3 to 6 carbon atoms in the ring, and examples thereof are cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

The indication halo (C ₁ -C.) Alkyl, for example, relates to trifluoromethyl, bromomethyl, 1,1-difluoroethyl, Pentaflur- 'ethyl, 1,1,2,2-tetrafluoroethyl, chlorodifluoromethyl _t trichloromethyl, 2-bromoethyl, chloromethyl, 3-Bromopropyl, 4-bromobutyl, 3-chloropropyl or 3-chlorobutyl.

Examples of halogen (C ₁ -C ₉ ) alkyl are trifluoromethyl, bromomethyl, chloromethyl, 1,1-difluoroethyl, 'pentafluoroethyl, T, 1,2,2-tetrafluoroethyl, chlorodifluoromethyl, trichloromethyl or 2-bromoethyl.

By C ₁ -C ₃ -alkoxy is meant ilethoxy or ethoxy.

By C ₁ -C ₄ -alkoxy is meant methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, s-butoxy, isobutoxy or t-butoxy.

The statement C ..- C ₂ alkylthio refers to methylthio or ethylthio.

C, -C.alkylthio is understood as meaning methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, s-butylthio or t-butylthio. ,

Examples of C 1 -C 4 -alkylsulfonyl are methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl or butylsulfonyl.

Examples of C.-C ₄ alkylsulfinyl are methylsulfinyl, ethylsulfinyl, n-Propylsulf.inyl, Isopropylsulf ynyl or Butylsulf ynyl

Specific examples of new compounds falling within the above formula II are as follows:

1- (2-bromobenzoyl) -3- / 5- (alpha, alpha, alpha-trifluoro-m-tolyl) -

6-methyl-2-pyrazine-1-urea f,

1- (2-methylbenzoyl) -3- / 5- (alpha, alpha, alpha-trifluoro-p-tolyl) -6-methyl-2-pyrazinyl / urea;

1- / 5- (alpha, alpha, alpha-trifluoro-m-tolyl) -2-pyrazinyl / -3- (2-chlorobenzoyl) urea,

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

1- (2-bromobenzoyl) -3- / 5- (alpha, alpha, alpha-trifluoro-p-toiyl) -? - pyrazinyl / urea,

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

1- (5-cyclopentyl-6-methyl-2-pyrazinyl) -3- (2-methylbenzoyl) -hernstoff,

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,

-ie- 206203

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

1- (2-chlorobenzoyl) -3- / 5- (4-chlorophenylthio) -o-methyl-Z-pyrazinyl / urea;

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

The novel compounds of formula II are insecticidally active as they interfere with the growth of the insects that respond to them. The compounds appear to disrupt the insect's skinning process, killing them. The compounds exert their effect on insects "in that the insects digest these compounds, for example the leaves or the foliage treated with the respective active compounds or also other parts of their usual habitat, such as water, manure or similar carriers containing active ingredient Because of this behavior, the present compounds are especially useful for controlling insects in the larval state.

Surprisingly, the novel compounds of formula II also show systemic activity in plants which have been treated with them. When one of the novel insecticidally active compounds is applied to an old leaf of a plant, for example a soybean plant, the insecticidally active compound in the soybean plant is transferred to the new growth of the plant and even into the main stem of the plant. However, there is no systemic transmission of the insecticidally active compound when treating the roots of soybeans or other plants with this compound.

20 6 203

It has also been shown that certain compounds which fall under the formula II, are also ovicid effective. These are those compounds of the formula II in which

A ^{1 is} bromine or chlorine,

R is hydrogen, trifluoromethyl or. ,

is

7 -

R is hydrogen, chlorine, methyl or trifluoromethyl

represents,.

R is hydrogen, halogen, methoxy, trifluoromethyl

or phenyl,

q is O or 1 and

ρ stands for O

The novel compounds of the formula II are prepared in a manner known per se.

To prepare the compounds of formula II, a corresponding -2-aininopyrazine is reacted with a 2-substituted-benzoyl isocyanate to give the corresponding 1- (mono-o-substituted-benzoyl) -3- (substituted-pyrazinyl) -urea. The reaction is carried out at about 0 ^° C. to 70 ^° C., conveniently at about room temperature, over a period of time sufficient for the practical completion of the reaction. The reaction time required for this depends on the reactants used in each case and may depend on the time during which

Adding the reactants and mixing them together will take up to 48 hours. The reaction is carried out using a suitable solvent. For this purpose, inert solvents come into question, which do not react with any of the ongoing reactions 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 will be described below.

2-Chlorobenzoyl isocyanate is reacted with 2-amino-5- (4-bromophenyl) -6-methylpyrazine in cold ethyl acetate. The reaction mixture is stirred overnight at room temperature. The resulting product is isolated by filtration and purified by recrystallization from a suitable solvent such as ethanol. The product thus obtained melts at about 230 to 232 ^° C. On the basis of NMR and IR spectra and an elemental analysis, these are 1- (2-chlorobenzoyl) -3- / 5- (4-bromophenyl-6-methyl -2-pyrazinyl./harnstoff.

For the preparation of a compound of the formula II, it is also possible to react a 2-substituted benzamide with a 2-pyrazinyl isocyanate in a suitable solvent while maintaining the above-described reaction conditions and the above-mentioned reaction times. By reaction of 2-chlorobenzamide 5-Trifluormethylpyrazin-2-yl isocyanate leads such as to 1- (2-chlorobenzoyl) -3 -. (5-trifluoromethyl-2-pyrazinyl) urea, melting at about 219-220 ⁰ C. , '

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

To prepare the 2-substituted-benzoyl isocyanates, for example, corresponding 2-substituted-benzamides are reacted by the process described in J. Org. Chem. 27, 37 4 2 (1962). "';

The required in the present process benzamides, phenyl chloroformates, anilines, aminopyridines and lithium compounds are also either commercially available or can be prepared by methods known per se. The pyrazines and the benzopyrazines (quinoxalines) can be prepared in the usual way. ·

One of the required intermediates, namely 2-amino-5-chloro-pyrazine, can be prepared by the method described in J. Org. Chem. 29, 2491 (1964). For this purpose, methyl 2-amino-3-pyrazinylcarboxylate is reacted with chlorine in acetic acid to give methyl 2-amino-5-chloro-3-pyrazinylcarboxylate. Hydrolysis of this ester with aqueous sodium hydroxide gives 2-amino-3-carboxy-5-chloropyrazine, which gives the desired 2-amino-5-chloropyrazine by subsequent heating in tetrahydronaphthalene and decarboxylation.

Another intermediate, 2-amino-5,6-dichloropyrazine, can be prepared by reacting α-amino-δ-chloropyrazine with N-chlorosuccinimide in chloroform to give a mixture of 2-amino-5,6-dichloropyrazine , 2-amino-3,6-dichloropyrazine and 2-amino-3,5,6-trichloropyrazine. Subsequent column chromatographic 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 the literature cited therein.

Other 2-amino-5 (or 6) -substituted-pyrazines which are suitable for the preparation of the novel end products of the formulas I or II,

can be formed using oxime derivatives of certain ketones. 2-0xopropanal-1-oxime and 2-0xobutanol-1-oxime can be prepared, for example, from ethyl acetoacetate or ethyl propioacetate according to Chem. Ber. 11, 695 (1878). Other intermediate oximes may be prepared from ketones such as acetophenone, 2,4-dimethylmethylacetophenone, p-chloroacetophenone and benzyl methyl ketone, according to the method described in Chem. Ber. 20, 2194 (1887). Yet other oximes can be prepared from ketones such as p-methoxypropiophenone, p-bromobutyrophenone, p-bromopropiophenone and methyl neopentyl ketone, according to the method described in J. Am. Chem. Soc. 51, 2262 (1929).

Another intermediate oxime can be prepared from t-butyl methyl ketone with conversion into t-butylglyoxal according to J. Am. Chem. Soc. 61, 1938 (1939) form. 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. Subsequent work-up of the reaction mixture by extraction with ether and isolation of the t-butylglyoxaloxime from the ether extract gives colorless needles, which melt at about 50 to 52 ⁰ C.

The required as an intermediate 2-amino-5-methylpyrazine, starting from 2-0xopropanal-1-oxime, prepared stepwise. For this purpose, this oxime is first reacted with aminomalonic acid nitriloyl (prepared according to J. Am. Chem. Soc., 88, 3829 (1966) to give 2-amino-3-cyano-5-methylpyrazine-1-oxide 1-oxide is reacted with phosphorus trichloride to give 2-amino-3-cyano-5-methylpyrazine, followed by hydrolyzing this 2-amino-3-cyano-5-methylpyrazine with aqueous sodium hydroxide to give 2-amino-3 By decarboxylating this compound in tetrahydronaphthalene, the desired 2-amino-5-methylpyrazine is obtained.

2-amino-5-ethylpyrazine can also be prepared by the same general procedure and starting from 2-0xobutanal-1-oxime.

Another pyrazine intermediate, namely 2-amino-5- (4-bromophenyl) -6-methylpyrazine, can be prepared starting from 1- (4-bromophenyl) -1,2-propanedione ~ 2 ~ oxime, this oxime being prepared according to the method of US Pat in J. Am. Chem. Soc. 51, 2262 (1929). The oxime is first reacted with Aminomalonsäurenitriltosylat, followed by reacting the product obtained as a product substituted pyrazine-1-oxide according to the method described in J. Org. Chem. 38, 2817 (1973) with phosphorus trichloride in tetrahydrofuran. The resulting 2-amino-3-cyano-5- (4-bromophenyl) -6-methylpyrazine is then hydrolyzed in sodium hydroxide and ethylene glycol oil, after which the resulting 2-amino-3-carboxy-5- (4-bromophenyl) ~ 6-methylpyrazine decarboxylated by heating in tetrahydronaphthalene. In this way one arrives to 2-AmInO ^ -S- (4-bromophenyl) -6-methylpyrazine. ,

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

Other pyrazine intermediates can be prepared starting from 2,5-dichloropyrazine, which can be formed by the method described in J. Org. Chem. 29, 24, 91 (1964). This 2,5-dichloropyrazine can be used as a starting material for the preparation of the phenoxy- or phenylthio-substituted-pyrazines required as intermediates or the corresponding substituted phenoxy- or phenylthio-substituted-pyrazines. In particular, this is done by adding 2,5-dichloropyrazine 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., to give the corresponding Chloro-5-phenoxy- (or -phenyl- thio) pyrazine is obtained. This 2 ~ chloro-5 ~ phenoxy (or -phenylthio) -

²² ". 20 6 203

pyrazine can be converted to the corresponding 2-airiino-5-phenoxy (or phenylthio) pyrazine by reacting it with ammonium hydroxide at about 150 to 200 ° C in a high pressure reaction vessel for sufficient time to complete the conversion conveniently. That _; 2-amino-5-phenoxy (or phenylthio) pyrazine thus obtained is then used to prepare the 1- (substituted-benzoyl) -3- / 5-phenoxy (or phenylthio) -2-pyrazinyl-ureas. Homologous phenoxy or phenylthio compounds can also be prepared in the same way. -

The required as an intermediate 2-chloro-5-phenylthiopyrazin 'or a corresponding homologue thereof can be oxidized using oxidizing agents such as peracetic acid or m-chloroperbenzoic acid, the corresponding intermediate 2-chloro-5-phenylsulfinylpyrazin or 2-chloro-5-phenylsulfonylpyrazine , For example, acetic acid, chloroform or methylene chloride are used as the solvent. The oxidation is conveniently carried out at temperatures between about 20 and 70 ⁰ C.

If the ^ -chloro-S-phenylsulfonylpyrazine or 2-chloro-5-phenylsulfinylpyrazine obtained in the above manner is then reacted with ammonia or ammonium hydroxide in a high-pressure reaction vessel at about 100 to 200 ^° C., the intermediates 2-amino-5 are obtained. phenylsulfonylpyrazine or 2-amino-5-phenylsulfinylpyrazine. The reaction conditions to be used are different depending on the chemical structure of the phenylsulfonyl moiety or the phenylsulfinyl moiety.

Also, the 2-aminoquinoxalines, which are simply aminobenzopyrazines, can be prepared by known methods. The production of 2-aminoquinoxaline. For example, by reacting the commercially available 2-chloroquinoxaline with ammonia in a suitable solvent, such as ethanol, at water bath temperature.

Other quinoxalines required as starting materials are prepared from o-phenylenediamines which are commercially available 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. For this purpose, 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 to. For example, 5-cyano-3-nitro-p-phenylenediamine can be prepared by selectively hydrogenating 4-cyano-3,5-dinitroaniline in the presence of 5% ruthenium-on-carbon in ethanol as a solvent together with water-free hydrazine. According to the same general procedure, 3-nitro-5-trifluoro-methyl-o-phenylenediamine can also be prepared from 2,6-dinitro-4-trifluoromethylaniline.

Other o-phenylenediamines useful in the preparation of the quinoxaline intermediates required for the synthesis of the novel compounds of Formula I may be prepared by reduction of commercially available o-nitroanilines using 5% palladium on carbon catalyst in one Niederdruckhydrierapparatur be prepared. By appropriate hydrogenation of 2-nitro-4-trifluoromethylaniline obtained, for example, 4-trifluoromethyl-o-phenylenediamine.

2-amino-6-chloroquinoxaline or 2-amino-7-chloroquinoxaline can be prepared by known methods, and for example, The Chemistry of Heterocyclic Compounds, Condensed Pyridazines and Pyrazines Rings, Part III, Quinoxalines, Chapter XXIVff, page 2O3ff, by JCE Simpson / Arnold Weissberger, Consulting Editor, Interscience Publisher, Inc., New York (1953), and an example of such a manufacturing process is as follows:

3,4-Diaminochlorobenzene is reacted with glyoxylic acid to give a mixture of 6-chloro-2-hydroxyquinoxaline and 7-chloro-2-hydroxyquinoxaline. By reacting this mixture with phosphorus oxychloride, a mixture of 2,6-dichloroquinoxaline and 2,7-dichloroquinoxaline is obtained. If this mixture is allowed to react with anhydrous ammonia in a suitable solvent, preferably dimethyl sulfoxide, then a mixture of 2-amino-6-chloroquinoxaline and 2-amino-7-chloroquinoxaline is obtained. '·

embodiments

The invention will be further illustrated by the following examples.

example 1

1- (2,6-dichlorobenzoyl) -SA ^ -methyl-S- (4-brömphenyl) -2-pyrazinyl / - urea

A solution of 304 mg of 2,6-dichlorobenzamide and 25 ml of dry tetrahydrofuran is added to a 50 ml three-neck 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. Over a period of 5 minutes, the resulting solution is then treated with 0.6 ml of n-butyllithium. After completion of the addition, the reaction mixture is stirred for 30 minutes at about -72 ⁰ C on. The mixture is then added dropwise over a period of 15 to 20 minutes with a solution of 268 ml of 4-nitrophenyl chloroformate in 8 ml of dry tetrahydrofuran. It forms a pale yellow solution. After completion of the addition, the reaction mixture is stirred for 30 minutes at about -72 ⁰ C, whereby one arrives at a colorless solution. Then set the cooling bath so that the temperature increases 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 over a period of 10 minutes dropwise with a solution of 351 ing

2-amino-5- (4-bromophenyl) -6-methylpyrazine in 6 ml of dry tetrahydrofuran. Then remove the cooling bath and let the mixture come to room temperature. The mixture is then heated to 50 ° C for 16 hours to complete the reaction. The solvent is then removed under vacuum 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 brine. 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, after which the solution is concentrated under vacuum to an oil. The oil is treated with ether and the resulting solution is cooled. In the form of two harvests, this results in a total of 240 .mg of product. Recrystallization of this product from tetrahydrofuran-ether leads to 132 mg of material which melts at 225 to 227 ⁰ C. From the filtrate is obtained by preparative thin layer chromatography, a further 69 mg of product.

Example 2 1- (2,6-Dichlorobenzoyl) -3- / 5- (4-chlorophenyl) -2-pyrazinyl / urea

The procedure described in Example 1 is repeated using 273.5 mg of 2-amino-5- (4-chlorophenyl) pyrazine instead of 2-amino-5- (4-bromophenyl) -6-methylpyrazine. In this way, 222 mg of the title compound, which melts at 245 to 249 ⁰ C is obtained.

20 6 203

Example 3

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

pyrazinyiyharnstoff

The procedure described in Example 1 is repeated using 336.8 mg of 2-amino-5- (3-trifluoromethylphenyl) -6-methylpyrazine instead 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, resulting in a viscous oil which crystallizes on standing to a white solid. The solid is treated nit cold ether and then filtered, thereby obtaining a first crop, 62 mg of a white product melting at 182-185 ⁰ C *. The filtrate is allowed to evaporate to concentrate in a fume hood, yielding a yellow oil. Crystallization of this oil from ether yields 102 mg of a white solid as a second crop. The total yield is 164 mg.

Example -4 1- ( 2,6-Dichlorobenzoyl) -3- (6-trifluoromethyl-2-pyraζinyl) urea

The procedure described in Example 1 is repeated using 217 mg of 2-amino-6-trifluoromethylpyrazine instead of 2-amino-5- (4-bromophenyl) -6-methylpyrazine. The product obtained is worked up as described in Example 3. The resulting oil in the preparative thin layer chromatography crystallized on standing at room temperature. The crude solid is treated with cold ether and the resulting crystalline solid is filtered off. In this way one arrives at 144 mg product, melting at 188-192 ⁰ C.

Example 15 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-neck round bottom flask. The solution is cooled with an Trockeis-acetone bath to about -72 ⁰ C. The reaction mixture is treated with 1.8 ml of n-butyllithium solution over a period of 5 minutes. Then allowed the reaction mixture for 30 minutes at -75 to -70 ⁰ C stand. Over a period of 30 minutes is then added at a temperature of about -72 ⁰ C, a solution of 0.804 g of 4-Nitrophenylchlorformiat in 24 ml of dry tetrahydrofuran to. Then allowed to stand the mixture for a further 30 minutes in the cold, where it is 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 come to room temperature, after which they are heated to 50 ⁰ C for 16 hours. The solvent is removed and the residue is dissolved in 10 ml of ether. The solution is washed with 1N 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 white crystalline solid, which melts at about 200 ⁰ C.

Analysis:

calculated: C 47.77; H, 2.41; N, 7.43; ,

Found: C 46.85; H 2.62; N 7,20.

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 in a cast at a temperature of -30 ⁰ C with 1.8 ml of 2.4 molar n ~ Butyllithiumreagenz. The mixture is then added over a period of 10 minutes at -40 ⁰ C with a mixture of 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). ¹ Subsequently, the solution is kept at -35 to -30 ⁰ C and treated over a period of 5 minutes with a solution of 0.8 g of 4-aminobenzotrifluoride in 25 1 dry tetrahydrofuran. The Lösimg is then heated for 4 hours at reflux temperature (about 60 ⁰ C). The mixture is diluted with 300 ml of ether, then washed five times with sodium carbonate solution, dried and the solvent removed. Recrystallization from ether-hexane gives 0.72 g of product which melts at 205 ^° C. (not sharp).

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 added at a temperature of -70 to -75 ⁰ C in a mold with 5.0 ml of n-butyllithium solution. 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-

(p-nitrophenyl) carbamate in 25 ml of dry tetrahydrofuran. Then the solution is allowed to come to -30 ⁰ C, it keeps for 1 hour at this temperature and then allowed to come to room temperature. Subsequent thin-layer chromatographic analysis shows that the desired product has been formed. The product is isolated as described in Example 6 to give 2.20 g of material which melts at 200 ^° C. (not sharp).

The following preparations describe the preparation of the substituted benzoyl isocyanates and pyrazines required as intermediates, which are needed to prepare the novel compounds of formula II.

Creation ^ 1

2-Chlorbenzoylisocyanat

This compound is prepared by the method described in J. Org. Chem. 27, 3742 (1962).

A solution of 10 g of 2-chlorobenzamide (commercially available) in 100 ml of methylene chloride is first formed. The resulting solution is then mixed very slowly with 25 ml. Oxaly! Chloride. The mixture is heated at reflux temperature overnight. The reaction is cooled, filtered, and the filtrate is evaporated to remove the ethylene chloride solvent. The resulting oily residue is identified by the IR spectrum as 2-chlorobenzoyl isocyanate and used without purification for the preparation of the novel compounds of formula I.

Following the same general procedure as in Preparation 1 above and starting from 2-methylbenzamide or 2-bromobenzamide, both of which are commercially available, the following further compounds are identified which are identified by their IR spectra:.

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

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

Preparation 4 2-Amino-5-chloropyrazine

This connection is made gradually. The first stage will be after the one in Ann. 660, 98-103 (1962). ·

Specifically, this is heated to a mixture of 7.5 g of 2-amino-3-carboxypyrazine, 8.9 g of 1-methyl-3-p-tolyltriazine and 250 mg of tetrahydrofuran for about 4 hours at reflux temperature. The reaction mixture is then cooled and filtered to discard the solid remaining on the filter. The filtrate is evaporated to dryness under vacuum and the residue is treated with a small amount of ethyl ether. The thereby separating solid is collected. It weighs about 7 g and melts at about 166 to 169 ⁰ C. Because of an IR spectrum, this is methyl 2-amino-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 water-free chlorine, where keeping the temperature of the reaction mixture at about 35 to 40 ⁰ C. The reaction mixture is then cooled and filtered. The resulting solid is stirred for 1 hour in a mixture of 30 ml of water and

-31- 206203

4.6 g of sodium sulfite are stirred, whereupon the whole is filtered. The collected solid is stirred in a mixture of ice and water followed by refiltering. Based on an NMR spectrum, this solid is methyl 2-amino-5-chloro-3-pyrazinylcarboxylate "The material" is used without further purification.

According to the method described in J. Org. Chem. 29, 2491 (1964), the above methyl 2-amino-5-chloro-3-pyrazinylcarboxylate is first hydrolyzed and then decarboxylated.

For this purpose, a mixture of 1.6 g of methyl 2-amino-5-chloro-3-pyrazinylcarboxylate and 50 ml of 2 normal aqueous sodium hydroxide is refluxed for about 1.5 hours. The reaction mixture is then cooled and filtered. The collected solid is dissolved in 25 ml he.ißem water, whereupon the solution is filtered and the filtrate acidified with concentrated aqueous hydrochloric acid. The precipitated solid is filtered off and dried. It weighs 1.3 g and melts at about 177 ⁰ C with decomposition. Based on an IR spectrum, these are 2-amino-3-carboxy-5-chloropyrazine. This compound is used for the next step without further purification. ,

A mixture of 500 mg of 2-amino-3-carboxy-5-chloropyrazine and 9 ml of tetrahydronaphthalene is heated at reflux for about 1 hour. The reaction mixture is then cooled and filtered. The resulting solid is washed with hexane. The solid melts at about 121 to 123 ⁰ C with decomposition, and it is due to an NMR spectrum of 2-amino-5-chloropyrazine.

-32- 20 6 203

Preparation 5 2-Amino-5,6-dichloropyrazine

A mixture of 5 g of 2-amino-6-chloropyrazine (commercially available), 10.3 g of N-chlorosuccinimide and 100 ml of chloroform is heated at reflux temperature for about 1.5 hours. The reaction mixture is cooled and filtered to discard the solid remaining in the filter. The filtrate is evaporated and the residue washed with water and hot aqueous sodium bisulfite solution. The solid formed in this treatment is filtered off. Subsequently, this solid is chromatographed on a column packed with 5 × 8 mm pellets of a copolymer of styrene and divinylbenzene using chloroform as solvent and eluant. This chromatography gives .man the following three compounds:. ·

Compound 1, having a melting point of about 132-135 ° C, identified as 2-amino-3,6-dichloropyrazine.

Compound 2, having a melting point of about 132 to 134 ^° C, identified as 2-amino-3,5,6-trichloropyrazine.

Compound 3, having a melting point of about 143 to 144 ^° C, identified as the desired 2-amino-5,6-dichloropyrazine.

Production 6 2-amino-5 ~ phenyl ~ 6-methylpyrazine

This intermediate pyrazine is prepared by a stepwise process.

In the first stage, a mixture of 6.5 g of 1-phenyl-1,2-propanedione-2-oxime (commercially available) and 10.1 g of amino-lipoalcohol are stirred.

Acid nitrilosylate in 6O ml of isopropyl alcohol overnight at room temperature. The. Reaction mixture is then filtered, yielding 7 g of solid. This solid is an NMR spectrum of 2-amino-3-cyano-5-phenyl-6-methylpyrazine-1-oxide.

A mixture of 7 g of the pyrazine-1-oxide prepared in the above manner and 250 ml of tetrahydrofuran is cooled to about 0 ⁰ C and slowly added with 40 ml of phosphorus trichloride. After completion of Ztigabe the reaction mixture is stirred overnight at room temperature. The mixture is then concentrated under vacuum to a volume of about 50 ml, after which the concentrate is poured into 1 liter of a mixture of ice and water. The precipitated solid is filtered off. This gives 1 g of 2-Air.ino-3-cyano-5-phenyl-6-methylpyrazine.

In the next step, a mixture of 1 g of 2-amino-3-cyano-5-phenyl-6-methylpyrazine (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, added with water and neutralized to pH 5 to 7. The precipitated .Feststoff is collected. Based on an IR spectrum, these are 2-amino-3-carboxy-5-phenyl-6-methylpyrazine. This solid is used directly for the next stage of the process. '';

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

Following the same general procedure as in Preparation 6 and using the specified oximes as starting materials according to the methods described in J. Am. Chem. Soc. 51 , 2262 (1929), more pyrazines are used as intermediates. These pyrazines are identified by their NMR and IR spectra, and are the following compounds:

7. 2-Amino-5- (4-methoxyphenyl) -6-methylpyrazine from T- (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 i-H-bromophenyl) -1,2-propanedione-2-oxime.

TO. 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-tolyl) -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.

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

17. 2-Amino-5- (4-itiethylthiophenyl) -6-methylpyrazine from 1- (4-methylthiophenyl) -1-propanedione - ^ - oxime.

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

Following the general procedure described in Preparation 6 using the following oximes, which are described in Chem. Ber. 20, 2194 (1887), the following further intermediate pyrazines are prepared which are 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-5α (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-ethylphenyl) pyrazine from 4-ethylphenylglyoxaloxime.

25. 2 ~ Άΐΐ [± ηο-5- (4-t-butylphenyl) pyrazine from 4-t-butylphenylglyoxaloxime.

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

20 6 203

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

This intermediate pyrazine is prepared in stages. · ',,

The first step consists of reacting 4-bromobutyrophenone according to the procedure described in J. Am. Chem. Soc. 51, 2262 (1929), resulting in 1- (4-bromophenyl) -1,2-butanedione-2-oxime, which is identified by IR and NMR spectra. .

In the second step, the 1- (4-bromophenyl) -1,2-butanedione-2-oxime thus obtained is further reacted according to the general procedure described in Preparation 6 to give 2-amino-5- (4- bromophenyl) -6-ethylpyfazine, which is identified by IR and NMR spectra.

Preparation 28 2-Amino-6-cyanopyra ζ in This intermediate is prepared in stages.

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

_ O "7 _

A mixture of 4 g of the pyrazine oxide obtained in the above manner in 4O ml of dimethylformamide is added rapidly with 12 ° ml of phosphorus oxychloride with cooling in an ice bath. The reaction mixture is poured into water and the aqueous mixture extracted with ethyl acetate, the extracts are removed. The aqueous layer is treated with more water and the aqueous mixture extracted with hexane-ether. The ethyl acetate and hexane-ether extracts are combined and concentrated under vacuum to a residue. The residue is identified by elemental analysis and IR spectrum as 2-chloro-6-cyanopyrazine, and this product is used without further purification for the next process step ,

A mixture of 1 g of the above obtained in the above manner Chlorcyanopyrazins and 25 ml of dimethyl sulfoxide forth and then introduced into this mixture anhydrous ammonia. 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 desiccant is filtered off and the solvent removed under vacuum to leave a solid which is 2-amino-6-cyanopyrazine due to its IR spectrum. This material is used without further purification to prepare compounds of formula I.

Production 2 9

2 - Amino-6-trifluoromethylpyrazine . · This intermediate is manufactured in stages.

After in Chem. Ber. 89, 1185 (1956), aminoacetamide dihydrochloride is first prepared. The further required 3,3-dibromo-1,1,1-trifluoropropanone is prepared according to the method described in J. Am. Chem. Soc. 74, 3902 (1952).

20 6203

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 at 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 of sodium hydroxide in 25 ml water. The reaction mixture is stirred and gradually heated to about 20 ^° C. over a period of about 2 hours. The mixture is then evaporated to remove the methanol under vacuum and the resulting residue 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 elemental analysis, this product is 2 - amino-6-tri- fluorine thypyr a ζ in.

* Analysis for C ₅ H ₄ FN ₃ :

calculated found

C 36.82% • H 2.47 N 25.76

Production 30

2-amino-5-trifluoromethylpyrazine -

A solution of 18 g of 4,5-diamino-6-hydroxypyrimidine sulphate (commercially available) in 180 ml of aqueous 3 normal sodium hydroxide is prepared and cooled, followed by cooling the cooled mixture with 25.2 g of 3,3-dibromo-1,1 , 1-trifluoropropanone. 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 ^ -prozentiger sulfuric acid and heated to about 135 ⁰ C for about 8 hours. The Re-

37, 11% 2, 17 25 52

action mixture is poured onto crushed ice, whereupon the aqueous mixture is neutralized with concentrated aqueous ammonium hydroxide. The solution is extracted with ethyl acetate. The ethyl acetate extracts are evaporated to dryness under vacuum, whereupon the resulting residue is recrystallized from a mixture of benzene and hexane. In this way, we arrive at 2.2 g of a product melting at about 118 to 122 ⁰ C. This product is 2-amino-5-trifluoromethylpyrazine based on NMR spectrum and elemental analysis.

Analysis for Cj-H.F-.N- .:

calculated found

C 36.82% H 2.47 N 25.76

Production 31

2-Amino-5-phenyl-6-trifluoromethylpyrazine This intermediate is prepared stepwise.

After in J. Het. Chem. 10, 697 (1973), 1-phenyl-3,3,3-trifluoro-1,2-propane monohydrate is first prepared.

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 aminoacetaminediindihydrobromide with stirring. With further stirring, then 8.6 ml of aqueous 2N sodium hydroxide are added. The reaction mixture is then stirred for about 2 hours at room temperature, after which it is stirred for about 4 hours under reflux temperature. The

37 , 04% 2 , 58 25 97

Reaction mixture is cooled and acidified with dilute aqueous hydrochloric acid. Then water is added thereto and the mixture is extracted with 100 ml of ethyl acetate. The ethyl acetate extract is dried over anhydrous magnesium sulfate, after which the drying agent is filtered off and the filtrate concentrated under vacuum. The residue thus obtained is dissolved in chloroform and the solution is chromatographed on a column filled with silica gel using chloroform as the eluent. 100 mg of material, which is 2-amino-5-phenyl-6-trifluoromethylpyrazine, is obtained from this vase.

Production 32

"^ ''

2-Amino-5- (4-bromophenyl) -6-chloropyrazine This compound is prepared stepwise. Stage 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. Then the reaction mixture is treated with a further 12 g of the above-indicated tosylate salt and stirred for 24 hours at room temperature on. Following this, the reaction mixture is mixed with a further 3 g of the tosylate salt and stirred for several days at room temperature on. The reaction mixture is then cooled and the precipitated solid filtered off. The solid is extracted with 2 l of boiling ethyl acetate and filtered off. The filtrate is concentrated under vacuum to about 900 ml. The solution is filtered again and then cooled. The thereby separating crystalline material is

- 41 - ZlTO

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

Level 2

A mixture of 60 ml of phosphorus oxychloride and 10 ml of dimethylformamide is added with stirring in small portions with 12.1 g of 2-amino-5- (4-bromophenyl) -3-carbethoxypyrazin-i-oxide (prepared in the above manner). After completion of the reaction, the reaction mixture is heated for about 15 minutes at reflux temperature, after which the excess phosphorus oxychloride is removed under vacuum. The residue is very carefully mixed with ice, whereupon the mixture is basified by the addition of 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 under vacuum. The residual black solid is extracted four times with 500 ml each of boiling cyclohexane. The combined cyclohexane extracts are concentrated to a volume of about 300 ml. The resulting beige solid melts at about 151 to 153 ⁰ C, and it is due to an NMR spectrum to 5- (4-bromophenyl) -3-carbethoxy-6-chloro-2- ./_ (dimethylamino) methylen./-imino pyrazine. The yield is 10.5 g.

level 3

A mixture of 12 g of 5- (4-Brompheriyl) -S-carbethoxy-G-chloro ^ - ./ (dimethvlamino) methylene / imino; pyrazine (prepared according to Stuv- ~)

Fe 2) and 150 ml of aqueous 2N hydrochloric acid is heated with stirring for about 5 minutes at reflux temperature, whereby a white precipitate formed. The mixture is cooled and treated with about 50 ml of aqueous 1N sodium hydroxide solution. The mixture is filtered off,

-42- 206203

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 elemental analysis, these are 2-amino-5- (4-bromophenyl) -3-carbethoxy-6-chloropyrazine , The yield is 10g.

analysis For C ₁₃ K ₁₁ BrClN ₃ O ₂ : found - calculated 43.90% C 43.79% 3.33 H 3.11 11.59 N 11.78 Level 4

A mixture of 10 g of 2-amino-5- (4-bromophenyl) -S-carbethoxy-öchlorpyrazin, 75 ml of dioxane, 75 ml of water and 8 g Nariumhydroxidplätzchen is briefly heated to reflux, with everything goes 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 recrystallization of a sample thereof from ethanol gives a melting point of about 212 to 214 ⁰ C. Based on an NMR spectrum and an elemental analysis, this is 2-amino-5- (4-bromophenyl) -3-carboxy-6 chloropyrazine. The yield is 9g.

Analysis for C ₁₁ H

calculated found

C 40.21% H 2.15 N 12.79

40 10% 2, 23 12 63

Level 5

A mixture of 9 g of 2-amino-5- (4-bromophenyl) -3-carboxy-6-chloropyrazine and 50 ml of tetralin is heated at reflux 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. Subsequent recrystallization of this solid from ethyl acetate leads to a product melting at about 254 to 256 ^° C. Based on an NMR spectrum, this is a 2-amino-5- (4-bromophenyl) -6-chloropyrazine. The yield is 4 g.

The following examples illustrate the preparation of the novel compounds of formula I.

Example 8

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

A mixture of 2.6 g of 2-amino-5- (4-bromophenyl) -6-methylpyrazine in 100 ml of ethyl acetate is treated with 2.0 g of 2-chlorobenzoyl isocyanate and stirred overnight at room temperature. Then the mixture is filtered. The resulting solid is recrystallized from ethanol to give a melting at about 230 to 232 ⁰ C material. Based on an elemental analysis and the NMR and IR spectra act. these are 1- (2-chlorobenzoyl) -3- / 5- (4-bromophenyl) -6-methyl-2-pyrazinyl./urea f.

Analysis calculated for C ₁₉ H ₁

, C 51, 20% H 3.17 N 12.57

found , 03% 51 , 37 3 , 62 12

-AA-

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

8A. 1- (2-chlorobenzoyl) -3- (5-trifluoromethyl-2-pyrazinyl) urea having a melting point of about 219 to 220 ⁰ C, starting from 500 mg of 2 ~ amino-5-trifluoromethylpyrazine and 600 mg of 2-chlorobenzoyl isocyanate. ,

8B. 1- (2-chlorobenzoyl) -3- (5-phenyl-2-pyrazinyl) urea, having a melting point of about 222-224 ⁰ C, starting from 1, Og of 2-amino ~ 5-phenylpyrazine and 1.0 g of 2-Chlorbenzoylisocyanat , , ':

8C. 1- (2-bromobenzoyl) -3- / 5- (4-bromophenyl) -6-methyl-2-pyrazinyl / urea having a melting point of about 220-222 ⁰ C ₇ starting from 2.0 g of 2-amino-5 - (4-bromophenyl) -6-itiethylpyrazine and 2.0 g of 2-bromobenzoyl isocyanate.

8D. 1- / 5- (4-bromophenyl) -6-methyl-2-pyraziny] L / -3- (2-methylbenzoyl) urea, having a melting point of about 247-248 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 having a melting point of about 212-214 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 -Chlorbenzoylisocyanat.

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 1.6 g 2 -Chlorbenzoylisocyanat.

8H. 1- (2-chlorobenzoyl) -3- / 5- (4-methylphenyl) -2-pyrazinyl / urea having a melting point of about 230-232 ⁰ C, starting from 600 mg of 2-amino-5- (4-methylphenyl ) pyrazine and 600 mg of 2-chlorobenzoyl isocyanate.

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

8J. 1- (2-chlorobenzoyl) -3- (6-methyl-5-phenyl-2-pyrazinyl) -urea, having a melting point of about 221-222 ⁰ C, starting from 500 mg of 2-amino-6 ~ methyl ~ 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-trifluoromethylpyrazine and 500 mg of 2-bromobenzoyl isocyanate.

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

'· · - 46 -

Example 9

1 - (2-chlorobenzoylo) -3- / 5- (4-chlorophenyl) -2-pyrazinyl-urea f

A solution of 0.5 g of 2-amino-5- (4-chlorophenyl) pyrazine is treated with 30 ml of dimethylformamide, after which the reaction mixture is stirred for about 3 to 4 hours at room temperature. The solution is then poured onto ice, whereupon the resulting precipitate is filtered off and washed with water. The crude material weighing 950 mg is recrystallized twice from a mixture of ethyl acetate and a small amount of dimethylformamide to give 200 mg of product which is approximately 231

- "melts to 234 ^° C. This product is 1- (2-chlorobenzoyl) -3- / 5- (4-chlorophenyl) -2-pyrazinyl / urea due to elemental analysis and NMR spectrum ,

analysis for C ₁₈ H ₁₆ Cl ₂ N ₄ O ₂ : calculated found C 55.82% 56.08% H 3.12 3.07 N 14.47 14.58

Following the general procedure outlined in Example 9 above and using appropriate starting materials, the following further compounds are prepared, which are identified by elemental analysis and NMR spectra:

9A. 1- (2-chlorobenzoyl) -3- / 6-methyl-5 ~ (alpha, alpha, alpha-trifluoro-m-tolyl) -2-pyrazinyl / urea having 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-trifluoromol-tolyl) -67-methylpyrazine and 1.3 g of 2-chlorobenzoyl isocyanate.

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

9C. 1- {2-chlorobenzoyl) -3- / 5- (2,4-xylyl) -2-pyrazine-urea having 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-methyl-bis-ethyl) -3- / 6-methyl-5-alpha, alpha, alpha-trifluoro-m-tolyl-2-pyrazinyl-urea having a melting point of about 211 to 212 g in an amount of 230 mg, starting from 0.5 g of 2-Air.ino-5- (alpha, alpha, alpha-tifluoro-m-tolyl) -6-methylpyrazine and 0.75 g of 2-Methylbenzoylisocyariat.

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

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

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

9H. 1 - / _ 5- (4-Bromo-phenyl) -6-ethyl-2-pyrazinyl-3- (2-chloro-benzoyl) -urea having a melting point of about 208 to 210 ^c in an amount of 270 mg, starting from 0.6 g 2-amino-5- (4-bromophenyl) -6-ethylpyrazine and 1.0 g of 1-chlorobenzoyl isocyanate.

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

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

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

212 ⁰ C in an amount of 0.7 g, starting from 0.6 g of 2-amino-5- (4 ^ -f luorphenyl) -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 to 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-ptolyl) -2-pyrazinyl / urea having a melting point of about

213 to 215 ⁰ 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.

- 49 - 2 0 6 2

Example '10

1- / 5- (3-bromophenyl) -6-methyl-2-pyraziny_l / -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 treated with 0.52 g of 2-chlorobenzoyl isocyanate with stirring. It immediately forms a solid precipitate. The reaction mixture is stirred for about 30 minutes, whereupon the solid is filtered off and recrystallized from a mixture of commercial absolute ethanol and dimethylformamide. In this way, 370 mg of a melting at about 201 to 203 ⁰ C product. Based on an NMR spectrum and elemental analysis, these are 1- / 5- (3-bromophenyl) -6-methyl-2-pyrazinyl / -3- (2-chlorobenzoyl) urea. "

analysis rur υ .. qii ^, - rircj 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 further compounds are prepared which are identified by elemental analysis and NMR spectra:

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

20 6 203

1Ob. 1- (2-chlorobenzoyl) -3- / 5- (4-methylthiophenyl) -6-methyl-2-pyrazinyl / urea f having a melting point of about 215 to 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 O, 22.G having a melting point of about 205-207 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 formula II are useful for controlling insects of various orders including Coleöptera, such as spotted. Ladybug, cotton boll beetle, corn root, beetle larva, cereal beetle, ground fleas, borer, Colorado beetle, corn beetle, Lucerne beetle, carpet beetle, meal beetle, beetle beetle, wireworm, rice beetle, rose beetle, plum grower or white larva of leaf horn beetle, Diptera, such as house fly, yellow fever mosquito, stable fly, horn fly , Blowfly, larva of cabbage fly or carrot fly, lepidoptera, such as cotton moth caterpillar, apple moth, caterpillar owl, clothes moth, cornmeal moth, curler larva, corn beetle larva, corn borer, larva of large cabbage white, cabbage tree, larva of cotton boll beetle, caterpillar of sack carrier, eastern tent caterpillar, Lawn moth caterpillar or caterpillar of autumn cotton moth, and Orthoptera, such as German cockroach or American cockroach.

It has now been found that the novel compounds of formula I according to the invention interfere with the mechanism of insect metamorphism, thereby killing the insects.

It has also been found that those compounds of formula II in which

A 'is bromine or chlorine,

R is hydrogen, trifluoromethyl or

is

R is hydrogen, chlorine, methyl or trifluoromethyl

represents,

R is hydrogen, halogen, methoxy, trifluoromethyl

or phenyl,

q stands for 0 or 1 and

ρ is 0,

ovicid are effective.

The novel compounds of the formula II are therefore suitable for controlling insects of the genera Coleoptera, Diptera, Lepidoptera or Orthoptera, by incubating the habitat of these insects with an insecticidally effective amount of a 1- (mono) -substituted-benzoyl) -3- ( Substituted pyraζinyl) urea s of the formula II treated.

The method of controlling such insects is in practice carried out by treating those sites where such insects live with an insecticidal agent which consists of an insecticidally effective amount of a compound of formula II and a solid or liquid carrier.

For the formulation of corresponding insecticidal agents from the novel compounds of the formula II, the respective active ingredient is either mixed with a solid carrier or dissolved or dispersed in a liquid carrier. If desired, aids such as surface-active substances and stabilizers can also be incorporated into such mixtures.

Such formulations may be aqueous solutions or dispersions, oil solutions and oil dispersions, pastes, dusts, wettable powders, miscible oils, granules or aerosols.

The wettable powders, pastes and miscible oils are concentrated formulations which are diluted with water before or during use.

To produce corresponding granules, the respective novel active ingredient to be used is taken up in a solvent and impregnated with the resulting solution then a corresponding granular support, for example, porous granules, such as pumice or attapulgite, mineral nonporous granules, such as sand or ground marl, or organic Granules, it being expedient to use a binder. Such preparations generally contain from about 1 to 15%, preferably about 5%, of active ingredient.

To prepare corresponding dust formulations, the respective active ingredient is mixed with an inert solid support 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, it also being possible to use mixtures of these and similar substances. Furthermore, organic carrier materials can also be used for this purpose, for example ground walnut shells.

For the preparation of wettable powder formulations is mixed about 10 to 80 parts by weight of a solid inert carrier, for example a carrier of the type mentioned above, with about 10 to 80 parts by weight of active compound, together with about 1 to 5 parts by weight of a dispersant, for example a lignosulfonate or a Alkylnaphtha.linsulf onats, and preferably also with about 0.5 to 5 parts by weight of a butcher, for example a fatty alcohol sulfate, an alkyl sulfonate or a fatty acid condensation product.

Miscible oil formulations are prepared by dissolving or suspending the active ingredient in a suitable solvent which is preferably immiscible with water after adding an emulsifying agent. 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. Suitable emulsifiers for the purpose are, for example, alkylphenoxypolyglycol ethers, polyoxyethylenesorbitan esters of fatty acids or polyoxyethylenesorbitol esters of fatty acids. These miscible oils contain the active ingredient in a concentration of about 2 to 50 percent by weight.

To prepare an aerosol preparation, it is possible to incorporate the active ingredient in the usual manner in the form of a solution in a suitable solvent in a volatile liquid suitable as a propellant, for example in a corresponding fluorocarbon.

The formulations containing an active ingredient of formula II may of course also contain other pesticidal compounds. 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 to be used to control insects in a plant-covered given area, of course, depends on a variety of factors, for example, the extent the vegetative surface to be treated, the level of infestation by insects, the condition of the foliage to be treated, and the temperature or humidity In general, it is recommended to use the active ingredient in a formulation having an active ingredient concentration of about G _{-1 to} l Contains 1000 ppm.

The insecticidal activity of the novel compounds of formula II has been tested by examination of corresponding formulations on caterpillars of the spotted ladybug (Epilachna varivesta) and caterpillars of the cotton moth (Spodoptera eridania). These insects are representatives of the orders Coleoptera and Lepidoptera. The compounds to be tested have been tested by several tests against these insects at application levels of from about 1000 ppm down to 1 ppm, by applying the compounds at these concentrations to the foliage of plants from which the larvae listed above were fed.

Trial 1 '.

The suitability of the novel compounds of formula I as insecticides is determined by the following method.

Bean plants are grown in approximately 10 cm square pots containing 6 to 10 plants per pot. Once the plants are 10 days old, they are used for the appropriate studies.

Each compound to be tested is formulated by dissolving 10 mg each of active ingredient in 1 ml of solvent (23 g of Toximul R + 13 g of Toximul S per liter of a 1: 1 mixture of anhydrous ethanol and acetone) and then mixing with 9 ml of water , In this way, drug solutions are obtained with an active ingredient concentration of 1000 parts per million (ppm). (Toximul R and Toximul S are surfactant mixtures of sulfonates and nonionic compounds and are manufactured by Stepan Chemical Company of Northfield, Illinois.) A portion of a test solution having an active ingredient concentration of 1000 ppm is then diluted in the ratio of 1:10 with the specified solvent to give a test solution with an active ingredient concentration of 100 ppm. The solutions of the compounds to be investigated with the respective active ingredient concentration are then sprayed onto the bean plants present in the individual pots. Then the plants are allowed to dry, 12 sheets are removed and the stems are wrapped in water-soaked cellulose. The leaves are then distributed on a total of 6 plastic Petri dishes, which are 100 χ 20 mm in size. In each case 2 larvae of larvae of spotted ladybug from the second appearance (Epilachna varivestis) and 5 larvae of the caterpillar of the cotton moth from the second

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%. Then the first results of the effect of the compounds to be investigated are determined. Following this, add two fresh larvae from the original treated pots to each Petri dish. The individual trays are then placed in a conditioning room with the above-mentioned temperature and humidity conditions for a further 3 days, followed by the corresponding assessment at the end of the seventh day. The percent control of insects is determined by measuring the number of live larvae per Petri dish. All treatments are compared to solvent controls and untreated controls. The test results are evaluated according to the following evaluation scale (percentage control):

0 = 0% combat

1 = 1-50% combat

2 = 51-99% control

3 = 100% control

The results obtained in the above tests are shown in the following Table I. In column 1 of this table, the compounds used are given by the number of their preparation example, while column 2 shows the application rates for the active substance in parts per million (ppm) and in columns 3 to 6 the evaluation values after 4 days and after 7 days for the -beiden mentioned there insects for the different drug concentrations, namely for the order quantities of 1000 ppm and 100 ppm, are indicated.

table

Order quantity appraisal values ma- Caterpillar of cotton wool moth 7th day ppm spotted beetle Day 4th day 3 Connection 1000 4th day 7. 3 3 3 8th 100 1 2 ' 3 2 1000 1 2 2 1 8Ά 100 1 1 1 2 1000 1 0   1 1 8B 100 0 0 0 3 1000 0 3 3 3 8C 100 0 2 " 3 3 1000 0 1 3 3 8D 100 0 0 3 3 1000 0 2 3 3 8E 100 0 3 3 2 1000 0 2 2 0 8F 100 1 1 0 2 1000 0 3 2 0 8G 100 0 2 0 0 1000 0 0. 1 0 8H 100 0 0 0 3 1000 0 2 3 3 81 100th 0 T _- 3 3 • 1000 0 1 3 2 ft 2 30 100 10.00 0 0 2 (N CM 2 8K LBO Q 2 2 2 • 2

- 58 Table I (cont'd)

appraisal values Day 7th day Caterpillar of the Baurapollmötte Day 7th day Mission-spotted mole beetle 0 2 4th 3 Connection ppm 4. 0 0 3 3 8L ' 1000 0 0 3 3 - 100 0 o: .3 U). 9 1000 2 3 3 3 100 1 2 2 3 9B 1000 0 0 2 1 100 ο 0 1 0 SC 1000 1 2 C 3 100 0 1 3 3 9D 1000 0 1 3 3 - 100 0 0 3 3 9E 1000 2 3 2 3 100 2 3 2 2 9F 1000 0 0 2 3 100 0 0 3 3 9G 1000 0 0 2 3 100 0 0 2 .1 9H 1000 2 2 0 2 100 1 2 2 1 91 1000 0 1 1 3 100 0 0 3 1 9J 1000th 0 100

Table I (continued) Assessment Values

Mission-spotted macaw of tree trunk beetle woolly moth

Verbin ppm 4th Day 7th day 4th day 7th Day dung 1000 0 3 - 3 3 10 100 0 • ι 2 2 1000 1 3 3 3 1OA 100 0 2   3 3 1000 1 3 2 3 1Ob 100th 0 .. 1 0 CN

Trial 2

Several of the new compounds of formula II tested in experiment 1 are reexamined but with lower application rates. The bean plants used for this purpose are prepared exactly as in Experiment 1. The compounds to be tested are formulated as follows:

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

By serial dilution of this solution is then formed in each case solutions containing the required for the experiments drug concentrations.

The solvent used is a 50:50 mixture of alcohol and acetone containing 23 g of Toximul R and 13 g of Toximul S per l.

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

Number of surviving animals in control

- Number of surviving animals at the percentage _ . treated Petri dish n .. "»

Combat. ^ ₂₃ I _{11 of the} surviving animals in control

The results obtained in the above tests are shown in the following Table II. Trial results based on more than one trial are indicated by means.

Table II

assignment percentage control cotton moth amount Caterpillar of: 7th day connection in ppm 4. Day 100 8th 100 100 100 50 100 ° 100 25 100 100 10 95 96 5 57 93 2.5 54 76 1.0 17 20 0.5 0 100 8C 100 100 100 50 100 100 25 100 100 10 100 100 5 100 100 2.5 100 93 1.0 60 73 0.5 20 100 8D 100 100 100 50 100 100. , 25 100 100 10 100 100 5 100 100 2.5 100 67 1.0 33 27 0.5 7

Table II (continued)

assignment percentage control Ba umwo1mmo tte amount Caterpillar of 7th day connection in ppm 4th day 100 8E 100 100 100 50 100 100 25 100 93 10 81 100 5 '80 47 2.5 27 100 81 - 100 100 100 .50 1-00 100 25 100 100 10 100 100 5 96 100 2.5 80 73 1.0 20 53 0.5 0 100 8L 10 100 75 5 13 • 100 9 100 100 , 100 50 93 100 25 93 100,. 10 57 76 5 30 27 2.5 13 0 1.0 0 7 0 5 7

T a b e 1 le II (continued)

Assignment- percentage control cotton moth amount Caterpillar of 7th day connection in ppm 4. Day 100 9A 100 100 100 50 100 100 25 100 100 10 100 100 5 100 100 2.5 93 80 1.0 20 40 0.5 23 100 9B 100 93 100 · 50 100 93 25 86 73 10 27 100 9D 100 100 100 50 100 100 25 100 100 10 100 100 5 100 100 2.5 100 100 1.0 53rd 100 9E 100 100 100 50 100 100 25 100 100  10 86 .73 5 27

'T from e- ^; Γ 1 e IT '(continued)

Assignment- percentage control Baümwollmotte amount Caterpillar of 7th day connection in ppm 4: day 47 2.5 27 27 1.0 20 100 9F 100 100 93 50 87 100 25 '93 93 10 67 100 9G - 100 100 100 50 "3 100 25 100 100 1 ° 80 100 9K 10 100 73rd 5 20 100 1OA 10 67 27 5 0

Trial 3

One of the compounds covered by the general formula II has also been studied against larvae of the Egyptian cotton leaf moth (Spodoptera littoralis).

The compound to be tested is dissolved in acetone for this purpose, and the resulting solution is diluted with water containing a surface-active agent.

The compound formulated in this way is then sprayed on a field of cauliflower plants. Subsequently, leaves are removed from the plants leaves and fed to it in the laboratory and collected from the field larvae of the Egyptian cotton leaf moth from the first to third appearance. The percent mortality values obtained here for the stated application quantities after the 4th day of the test and after the 7th test day are given in the following table. The compound used is indicated by the number of its preparation example.

table

III

Percent mortality

Larvae of the Egyptian

Cotton leaf moth

Order quantity from the 2nd appearance 7th day connection in ppm 4th day 100 8th 100 90 100 75 80 100 50 90 100 25 70

ZV O

After determination of the experimental values obtained after the 7th day, additional leaves are removed from the field crops of cauliflower plants and the residual activity of these leaves is determined in the manner already described above after the 4th day of the test and the 7th day of the test. The results obtained are shown in the following Table IV.

Table.

IV

Percent mortality

Larvae of the Egyptian

Cotton leaf moth

Order quantity from the 2nd appearance 7th day connection m ppm 4th day 100 8th 100 40 100 75 80 100 50 40 80 25 0

Trial 4

By this experiment, the local systemic activity of several compounds of formula II is to be determined.

The compounds to be tested are each formulated into 50% wettable powders. Each formulation is diluted with water to give the desired concentration of compound to be tested.

Sow soybean seeds (Variety Calland) and allow them to germinate. 7 days after sowing, when the cotyledons have developed, spray the soybean plants to drain off with the test solutions and then set the plants again for 1 week

into the hothouse. At the end of this week, the plants are harvested and sliced, separating the cotyledons (namely, the sprayed leaves) from the newly grown parts or the three-part leaves (new leaves) that developed within the 7 days following the spraying.

The sprayed leaves are placed in Petri dishes, the larvae of the caterpillar; The second and third cotton moths (Spodoptera eridänia) are contained, and the new leaves are placed in separate Petri dishes, which also contain larvae from the second and third species of the tree-wool moth caterpillar. Then you give the individual Petri dishes in a climatic 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 compounds to be tested. Following this assessment, the surviving larvae from the treated larvae or from the new larvae are transferred to clean petri dishes containing untreated soybean leaves. The Petri dishes are then placed in the climate chamber for a further three days until the final assessment is made after the 7th day.

The percent control values are determined as described in Experiment 2 above using the same formula. The results obtained are shown in the following Table V.

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

T e b e 1 1 e V

assignment percentage 'Combat 7th day New amount   · ' ' Caterpillar' the cotton moth sprayed 100 m ppm '' '4th day 100 94 connection 1000 sprayed New 100 28 8th 100 100 73 88 94 10 100 22 100 89 1000 29 0 100 22nd 8C 100 100 94 100 100 10 100 55 100 83 1000 47 0 100 22 SD 100 100 78 88 10 ioo 17 23 0

The above results show that in soybean transmission of the insecticidally active compounds occurs.

Trial 5

Several compounds of the formula II according to the invention are also tested for their activity as insecticides against yellow fever mosquito (Aedes aegypti) of the order Diptera.

To formulate each drug, each 10 mg of the compound to be tested in 1 ml of acetone and then mixed this solution with 99 ml of water, so that there is a test solution with an active ingredient concentration of 100 ppm. From this solution with an active ingredient concentration of 100 ppm is then formed by Se.rienverdünnung with water the required test solutions with lower drug concentrations. Each 40 ml of the test solutions obtained thereby are added

then in each case either in 100 ml glass beaker or in 16O ml Kufstoffbehälter container, wherein each drug concentration used two cups or containers. Each container is then filled with twenty 24-hour old mosquito larvae of the third appearance. The larvae are fed daily for a total of 7 days with 10 to 20 mg powdered Purina laboratory feed. During this time, the containers are left in a climate chamber, as used in experiment 1. After the 7th day of the experiment, the percentage mortality values for the mosquito larvae are determined by counting the living larvae. All treatments are compared to solvent controls and untreated controls. The results obtained are shown in the following Table V.

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

Table VI connection

Solvent untreated

Killing yellow fever mosquito larvae percentage mortality Order quantity in ppm O O O O O O O 0.01 0.01 0.01 1 -

Trial 6

By this experiment, the ovicidal activity of several compounds of formula II is determined, using egg clusters of the cotton moth caterpillar (Spodoptera eridania) and the spotted ladybird (Epilachna varvestis).

The egg grapes, which are on bean leaves of the variety Bountiful, are placed on a paper towel and sprayed under low air pressure (about 0.21 χ 10 dyn / cm ² ) with a DeVilbiss atomizer with the drug solutions. The active substance solutions used for this purpose are prepared as described in experiment 1. After spraying the eggs are blotted with a paper towel and placed together with a piece of a moist tooth tampon in corresponding plastic Petri dishes (60 χ 15 mm). Da.nn the eggs in the Petri dishes are incubated until the untreated controls hatched. At this point, the number of eggs that have hatched is determined. The test results obtained are determined in the form of percentages relative to the percentages of the controls. They are shown in the following Table VII.

In column 1 of this table, the compounds used are indicated by the numeral of their preparation example, while column 2 shows the order amount in parts per million (ppm) and column 3 indicates the percent kill values.

table

VII

Assignment Percent killing of eggs connection amount 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 100 500 100 250 100 100 100th 3J 1000 100 8K 1000 100 500 100 250 100 100 100 50 100 9A 1000 100 500 100 250 100 100 100

table

VII

(Continuation) Percent killing of eggs Lady bug Assignment Cotton moth connection amount in ppm 100 9B 1000 , 100 500 "95 250 100 100 100 100 9J 1000 100 96 9K 1000 100 96 500 • 100 250 100 100 100 50 100 25 96 10 100 5 100 10 1000

The experimental results show that the novel compounds covered by formula II are effective against a number of insects in the state of larvae. because the insects pick up the foliage or other parts of their environment, such as water or manure, which have been treated with active ingredient. Furthermore, the new compounds of formula II are also suitable as ovicidal agents.

Claims (26)

V £,% J CLAIMS INVENTION 1. Process for the preparation of 1- (mono-o-substituted benzoyl) -3- (substituted-pyrazinyl) ureas of the formula I. / O- HOHV υ ι - ti i > -C - N-C-N-R (τ) Chlorine, fluorine, bromine, methyl or trifluoromethyl, Is hydrogen, chlorine, fluorine, bromine, methyl or trifluoromethyl, R for / V I Il vv VVv ' (x) __. or rs stands, /. i. ^?: IVL; uöii κ- / b * 7! R is hydrogen, halogen, C 1 -C 6 -alkyl, halogen (C, -C ₄ -) alkyl), cyano,. means,. , 2 " R is hydrogen, halogen, methyl, ethyl, cyano or Is halogen (C ₁ -C ₄ ) alkyl, 3 4 ' R and R are the same or different and are hydrogen,. Halogen, C ₁ -C -alkyl, cyano or halogen (C ₁ -C ₄ ) -alkyl, R is halogen, halogen (C ₁ -C ₄ ) -alkyl, C ₁ -C -alkyl, cyano or phenyl, χ halogen, trifluoromethyl or Cj-C ^ alkyl, Y is halogen, Z represents oxygen or sulfur, η is 0, 1 or 2, ρ is 0 or 1 and m is 0, 1, 2 or 3, and of 1- (mono-o-substituted-benzoyl) -3- (substituted pyrazinyl) ureas of formula II / '. ο o A ^{1 is} bromine, chlorine or methyl, R is hydrogen, halogen, C 1 -C 6 -cycloalkyl, halogen (C 1 -C 4) alkyl, nitro, cyano, or Naphthyi is, R is hydrogen, halogen, methyl, ethyl, cyano or Represents halogen (C 1 -C ₂ ) -alkyl, with the proviso that the substituents R and R can not simultaneously be hydrogen, - / O - Sm <WW £. \ J Hydrogen, · halogen, halo (C ₁ -C ₄₎ alkyl, Cj-Cg alkyl, C.-C ^ alkoxy, C ₁ -C _f Cj-C nitro, cyano, phenoxy or phenyl -Alkylsülfinyl _4, stands for O, 1,2 or 3, " stands,
characterized , . that he (A) for the preparation of compounds of formula I between the radicals -C and-. · ..-. -R at. where A, B and R have the meanings given above, incorporate an ureido bridge by either (a) a benzamide of the formula is reacted with a Cj-C ^ -Alkyllithium and a Phenylchlorforraiat 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 in an inert solvent at about -80 to -40 · ⁰ C and the reaction mixture is then heated slowly to form the desired Benzoylharnstoffs and heated to about SO to 100 ⁰ C, or (b) a benzamide of the formula , with a C.-C ^ -Alkyllithium in an inert solvent at about -80 to -40 ⁰ C to form the corresponding lithium salt and this lithium salt is then reacted with a carbamate of an amine of formula KNEL · and a phenyl chloroformate, wherein this treatment in an inert solvent at about -80 to -40 ⁰ C with subsequent slow increase in the temperature to about 20 to 40 ⁰ C to form the desired Benzoylharnstoffs performs, or. (B) for the preparation of compounds of formula II between compounds of the formulas > · - __c-R and R ¹ ° s " wherein R and R are amino or isocyanate, first forms an ureido bridge, and the compounds which may subsequently be obtained in which X ^{1 is} -S-, then oxidized, if one wants to have compounds of formula II in which X ^{T is} for. 0 0 Il It -S or -S- Il 0 stands. 2. Method according to item 1, step (A), characterized in that the Üreido bridge between the radicals λ 0 \ _ö -C-NHs ^u P ^d - NHs-R, wherein A, B and R have the meanings given in point 1, forms according to the method of step (ä.). 3. The method of item 1, step (A), characterized in that the ureido bridge between the radicals / o -NH ₂ and. NH ₂ -R, where A, B and R are the ones in point. 1 given meanings according to the method of step (b) forms. 4. The method of item 1, step (A), characterized g e characterized in that one uses compounds in which the substituent B has a meaning other than hydrogen. 5. The method according to item 1, step (A), characterized in that one uses compounds in which the substituent R is for 1 2 wherein the substituents R and R have the meanings given in 'point. 6. The method according to item 1, step (A), characterized in that one uses a compound in which the substituent R is for where X and η are as defined in point 1 meanings
to have. 7. The method according to item 2, characterized in that the first part of the reaction at a temperature of about -75 to about -65 ⁰ C works and
the second part of the reaction at a temperature of about 50 to about 65 ⁰ C performs. 8. Process according to item 1, step (A), characterized in that n-butyllithium is used as the alkyl lithium. 9. The method according to item 1, step (A), characterized in that one uses a compound in which A and B are each chlorine. 10. The method according to item 1, step (B), characterized in that A ¹ , q, ρ and X ^{1 have} the meanings given in point 1, • · * R is hydrogen, halogen, C ₁ -C ₄ -cycloalkyl, halogeno (C ₁ -C ₄ ) -alkyl, O! or naphthyl, is: R. Represents hydrogen, halogen, methyl, ethyl or halogen - (C ₁ -C ₂ ) alkyl, with the proviso that the substituents R and R can not simultaneously be hydrogen, and R ⁸ 'is halogen, halo (C, -. _C4) alkyl, Cj-Cg-alkyl, C ₁ -C ₄ alkoxy, Cj-C ^ alkylthio, Cj - ^ - Alkylsulf ynyl, C ₁ alkylsulfonyl, nitro, or Cyano means. 11. The method according to item 1, step (B), characterized in that A ¹ , q and ρ have the meanings given in point 1, ^{R is} halogen, halogen (C ₁ -C ₂ ) -alkyl, C -C -cycloalkyl, β R ⁸ means' ^{R is} hydrogen, halogen, halogen (C ₁ -C ₃ ) alkyl or Represents methyl, ^{R is} hydrogen, halogen, halogen (C -C) alkyl, ^{Clk C} i ^'C ~ 2 ^{alkyl or} C ₁ -C ₂ -alkoxy and represents -O- or -S- 12. The method according to item 1, step (B), characterized ge ζ eich η e t that A ^{1 is} bromine, chlorine or methyl, R ⁶ for ^(CH 2 ⁾ p ° \ _{a: =; = a} / ⁰ Or cyclohexyl stands, .
R is halogen, halo (C ₁ -C ₂₎ alkyl, C.-C ~ ₂ alkyl or ₁₃ means' ρ stands for O, · q stands for 1 or 2 and. R is hydrogen or methyl, with the proviso that the substituent R is chlorine or bromine in 7
p position if R is hydrogen and q is 1 stands. 13. The method of item 1, step (B), characterized in that one works at a temperature of about 0 ⁰ C to about 70 ⁰ C. 14. The method according to item 1, step (B), for the preparation of 1- (2-chlorobenzoyl) -3- / 5- (4-bromophenyl) -6-methyl-2-pyrazinyl / -urea, characterized in that reacting 2-chlorobenzoyl isocyanate with 2-amino-5- (4-bromophenyl) -6-methylpyrazine. 15. The method of item 1, step (B), for the preparation of 1- (2-bromobenzoyl) -3- / 5- (4-bromopheny3) -6-methyl-2-pyraziny_l / -urea, characterized in that 2-amino-5- (4-bromophenyl) -6-methylpyrazine with 2-bromobenzoyl isocyanate. 16. The method of item 1, step (B), for the preparation of 1- (2-chlorobenzoyl) -3- / 5- (4-chlorophenyl) -e-methyl ^ -pyrazinyl / -urea, characterized in that 2-amino-5- (4-chlorophenyl) -6-methylpyrazine with 2-chlorobenzoyl isocyanate. 17. Process according to item 1, step (B), for the preparation of 1- (2-chlorobenzoyl) -3- / 5- (4-chlorophenyl-2-pyrazinyl / urea / d by which eich-net Amino-5- {4-chlorophenyl) pyrazine with 2-chlorobenzoyl isocyanate. 18. Process according to item 1, step (B), for the preparation of 1- (2-chlorobenzoyl) - - / o-methyl-o- (α, α, α-trifluoromol-2-pyrazinyl! / Urea , characterized in that reacting 2-amino-5- (alpha, alpha, alpha-trifluoro-m-tolyl) -6-methylpyrazine with 2-Chlörbenzoylisocyanat. 19. The method according to item 1, step (3), for the preparation of 1 ~ (2-methylbenzoyl) -3- / 5- (4-bromophenyl) -6-methyl-2-pyrazinyl / -urea, characterized in that 2-imino-5- (4-bromophenyl) -6-methylpyrazine with 2-methyl benzoylisocyanat. 20. The process of item 1, step (B), for the preparation of 1- (2-chlorobenzoyl) -3- / 5- (4-ethylphenyl) -6-methyl-2-pyrazinyl-1-urea, which is characterized by the formula in that 2-amino-5- (4-ethylphenyl) -6-methylpyrazine is reacted with 2-chlorobenzoyl isocyanate. . 21. Method according to item 1, step (B), for the preparation of 1- (2-chlorobenzoyl) -3- / 5- (4-methoxyphenyl) -6-methyl-2-pyrazinyl] _L / -urea, characterized that reacting 2-amino-5- (4-methoxyphenyl) -6-methylpyrazine with 2-chlorobenzoyl isocyanate. 22. Method according to item 1, step (B), for the preparation of 1- (2-methylbenzoyl) -3- / 5- (alpha, alpha, alpha-trifluoro-m-tolyl) -6-methyl-2-pyrazinyl urea, characterized in that reacting 2-amino-5- (alpha, alpha, alpha-trifluoro-m-tolyl) -6-methylpyrazine with 2HVlethylbenzoylisocyanat. 23. The method according to item 1, step (B), for the preparation of 1- (2-chlorobenzoyl) -3- (5-cyclohexyl-6-methyl-2-pyrazinyl) urea, characterized in that 2-amino-5 -cyclohexyl-6-methylpyrazine with 2-chlorobenzoyl isocyanate. ' 24. The method according to item 1, step (B), for the preparation of 1- (2-chlorobenzoyl) -3- / 5- (4-methylthiophenyl) -6-methyl-2-pyrazinyI ₁ / -urea, characterized in that reacting 2-amino-5- (4-methylthiophenyl) -6-methylpyrazine with 2-chlorobenzoyl isocyanate. 25. Process according to item 1, step (B), for the preparation of 1- (2-chlorobenzoyl) -3- / 5- (4-fluorophenyl) -6-methyl-2-pyrazinyl-3- _L- urea, characterized that reacting 2-amino-5- (4-fluorophenyl) -6-methylpyrazine with 2-chlorobenzoyl isocyanate. 26. The method according to item 1, step (B), for the preparation of 1- (2-chlorobenzoyl) -3- (5-trifluoromethyl-2-pyrazinyl) urea, characterized in that 2 ~ chlorobenzamide with 5-Trifluormethylpyrazin-2 -ylisocyanate is reacted.