DD143721A5 - INSECTICIDES MEDIUM - Google Patents

Description

1 3 690 -a

Field of application of the invention :

The invention relates to an insecticidal agent of a suitable inert carrier and an active ingredient in an insecticidally effective amount.

Characteristic of the known technical solutions :

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 Qrthoptera 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.

US Pat. No. 3,748,356 already describes a series of substituted benzoylureas which are said to be highly insecticidal. These compounds are generally 1 - (2,6-dichlorobenzoyl) -3- (substituted-phenyl) -ureas, but to this end, several 1- (2,6-dichlorobenzoyl) -3- (substituted-pyridyl ) ureas. belong.

US Pat. No. 3,989,842 discloses insecticidal compositions and methods for controlling insects in agriculture and horticulture, N- (2,6-dihalobenzoyl) -N ¹ - (substituted-phenyl) ureas being used as active ingredients and several others N- (2,6-dichlorobenzoyl) -N ¹ - (substituted-pyridyl) -ureas can be used.

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. For details, see Di'e Naturwissenschaften 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 and 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 highly insecticidal with respect to plant pests and are also intended to represent ectoparasiticides in veterinary medicine.

BE-PS 833 288 discloses insecticidally active disubstituted benzoylpyrazinyl ureas.

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 Pf3.anzentoxizität.

Aim of the invention ;

The aim of the invention is now to provide a new insecticidal agent which is superior to known insecticidal agents by a particular insecticidal activity.

Explanation of the essence of the invention :

The above object is achieved according to the invention in the insecticidal agent of the type mentioned in the introduction by using as active ingredient a 1- (mono-o-substituted-benzoyl) -3- (substituted-pyrazinyl) urea of the formula I.

s / Y

HH "

, ₄ 213 69C

contains, in which

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

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

(C ₁ -C ₄ ) alkyl, nitro, cyano,

-W ^q

or naphthyl,

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

Represents halogen (C ₁ -C ₀ ) alkyl,

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

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

C ₁ -C ₆ -alkyl, C ₁ -C ₄ -alkoxy, C ₁ -C ₄ -alkyl radical ¹ HiO, C ₁ -C ₄ -alkylsulfinyl, C ₁ -C ₄ -alkylsulfonyl, nitro, cyano, phenoxy or phenyl,

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.

Έί 3 of ©

The 1- (mono-o-substituted-benzoyl) -3-substituted-pyrazinyl ureas of formula I above represent novel compounds. They can be prepared by reacting the compounds of the formula.

9 wherein R and R is amino or isocyanate, first forming an ureido bridge and then optionally obtained compounds in which X ^{1 is} -S-, then oxidized, if one wants to have compounds of formula I in which X ¹ for

0 0

Il or Il -S f * Il 0

stands.

Preferred compounds according to the invention are those of the above formula I in which

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

R is hydrogen, halogen, C ₃ -C ₆ -cycloalkyl, halogen

(C ₁ -C ₄ ) alkyl,

⁰ -V / A

or naphthyl,

R · hydrogen, halogen, methyl, ethyl or halogen

Represents (C ₁ -C ₂ ) alkyl,

FZ. * "7

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

R ^{8 is} halogen, halogen (C ₁ -C ₄ ) alkyl, C ₁ -C 6 -alkyl, C ₁ -C.

Alkoxy, C ₁ -C ₄ -alkylthio, C ₁ -C ₄ -alkylsulfinyl, 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

II I!

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

II

stands.

More preferred according to the invention are those compounds of formula I above in which

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

R ^{6 is} halogen, halogen (C ₁ -C ₉ ) -alkyl, C ₁ -C -cycloalkyl,

-Y * φ ' ^ ₁ A ΟΟ.Θ3Γ ( ° li \ - ~ a

means

R is hydrogen, halogen, halogen (C 1 -C 4) alkyl or

Represents methyl,

R is hydrogen, halogen / halogen (C.C.sub.10) alkyl,

or C ₁ -C ₀ -alkoxy, q is O, 1 or 2,

ρ is O or 1 and

X ^{1 stands} for -O- or -S-.

Most preferred according to the invention are those compounds of formula I above in which A ^{1 is} bromine, chlorine or methyl, R ^{6 is}

"p ~ \ / * or cyclohexyl

R, halogen, halogen (C ₁ -C ₀ ) alkyl, C ₁ -C ₂ alkyl or

₁₃ means, stands for O, stands for 1 or 2 and

R is hydrogen or methyl,

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

p-Stel

stands.

7 p position must, if R 'is hydrogen and q for

^G / t f

ti » i

- 8th -

Halogen is understood in the above formula * I-fluorine, chlorine and bromine.

The term C ₃ -C 12 -cycloalkyl refers to cycloalkyl having 3 to 6 carbon atoms in the ring, and examples thereof are cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl.

The term halogen (C.-C.) alkyl refers, for example, to trifluoromethyl, bromomethyl, 1,1-difluoroethyl, pentafluoroethyl, 1,1,2,2-tetrafluoroethyl, chlorodifluoromethyl, trichloromethyl, 2-bromoethyl, chloromethyl, 3-bromopropyl , 4-bromobutyl, 3-chloropropyl or 3-chlorobutyl.

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

By C ₁ -C ₅ -alkoxy is meant methoxy or ethoxy.

C ₁ -C. Alkoxy is understood as meaning methoxy, ethoxy, propoxy, isopropoxy, n-butoxy, s-butoxy, isobutoxy or t-butoxy.

The term C. ~ C ₂ alkylthio refers to methylthio or ethylthio.

By C 1 -C 4 -alkylthio is meant methylthio, ethylthio, n-propylthio, isopropylthio, n-butylthio, isobutylthio, s-butylthio or t-butylthio.

Examples of C 1 -C 6 -alkylsulfonyl are methylsulfonyl, ethylsulfonyl, n-propylsulfonyl, isopropylsulfonyl or butylsulfonyl.

₉ pounds 1 <? 6V

Examples of C 1 -C 4 -alkylsulfinyl siad methylsulfinyl, ethylsulfinyl, n-p-propylsulfinyl, isopropylsulfinyl or butylsulfinyl!

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

1- (2-bromobenzoyl) -3- / 5- (alpha, alpha, alpha-trifluoro-m-tolyl) -6-methyl-2-pyrazinyl_ / urea;

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-tolyl) -2 - 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,

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

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

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

The novel compounds of formula I are insecticidal because 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 develop their activity in insects in that the insects digest these compounds, for example, the leaves or leaf treated with the respective active compounds or eat other parts of their usual habitat, such as water, manure or similar carriers which have been treated with active ingredient are, record. Because of this behavior, the present compounds are particularly suitable for controlling insects in the larval state.

The: novel compounds of the formula I 'surprisingly also show a 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.

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

A ^{1 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,

g is 0 or -1 and

ρ stands for 0.

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

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

Add the reactants and mix together, 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 2 30 to 232 ⁰ C. Based on NMR and IR spectra and an elemental analysis, this is 1- (2-chlorobenzoyl) -3- / 5- (4-bromophenyl-6- methyl-2-pyrazinyl _L / urea f.

For the preparation of a compound of the formula I 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 reaction times mentioned above. 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, 3742 (1962).

One of the required intermediates, namely 2-amino-5-chloropyrazine, 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 decarboxylic acid.

Another intermediate, namely 2-amino-5,6-dichloropyrazine, can be prepared by reacting 2-amino-6-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 required as starting material 2-amino-5-phenylpyrazine can according to Rec. Trav. Chiin. 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 formula I,

- .14 -

can be formed using oxime derivatives of certain ketones. 2-0xopropanal-1-oxime and 2-oxobutanol-1-oxime can be prepared, for example, from ethyl acetoacetate or ethyl propioacetate according to Chem. Ber. 11, 695 (1878). Other oximes which may be used as intermediates may be prepared from ketones such as acetophenone, 2,4-dimethyl acetophenone, 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-Oxopropanal-i-oxime, prepared stepwise. For this purpose, this oxime is first reacted with aminomalonic acid nitriloyl (prepared according to J. Am. Chem. Soc., 88, 3829 (19662) to give 2-amino-3-cyano-5-methylpyrazine ~ 1-oxide. Reacting 1-oxide 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-hydroxybenzyl. By decarboxylating this compound in tetrahydronaphthalene, the desired 2-amino-5-methylpyrazine is obtained.

According to the same general procedure and starting from 2-oxobutanal-1-oxime, 2-amino-5-ethylpyrazine can also be prepared.

Another pyrazine intermediate, namely 2-amino-5- (4-bromophenyl) -6-methylpyrazine, can be prepared from 1- (4-bromophenyl) -1,2-propanedione-2-oxime using this oxime 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, followed by the resulting 2-amino-3-carboxy-5- (4-bromophenyl) -6-methylpyrazine decarboxylated by heating in tetrahydronaphthaliri. This gives 2-amino-5- (4-bromophenyl) -6-methylpyrazine.

Exemplary embodiment e:

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

Preparation 1 2-Chlorobenzoyl isocyanate

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 of oxalyl 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 O-lige 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.

ty

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 prepared 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).

In detail, 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. Due to an IR spectrum, this is methyl 2-amino-3-pyrazinylcarboxylcit.

In the next step, a mixture of 2.8 g of methyl 2-amino-3-pyrazin.ylcarboxylate, 100 ml of water and 2 3 ml of glacial acetic acid is stirred at about 40 ⁰ C and passed into the resulting mixture for about 25 minutes anhydrous chlorine a, wherein the temperature of the reaction mixture is maintained 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

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-amino-S-chloro-S-pyrazinyl carboxylate is first hydrolyzed and then decarboxylated.

To this is heated a mixture of 1.6 g of methyl 2-amino-5-chloro-3-pyrazinylcarboxylate and 50 ml of 2 normal aqueous sodium hydroxide at reflux temperature for about 1.5 hours. The reaction mixture is then cooled and filtered. The collected solid is dissolved in 25 ml of hot water, the solution is filtered and the filtrate is acidified with concentrated aqueous hydrochloric acid. The 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 temperature 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.

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 5 χ .8 mm large pad of a copolymer of styrene and divinylbenzene column using chloroform as a solvent and Eiuiermittei. This chromatography gives the following three compounds:

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

Compound 2 with a melting point of etv / a 132 to 134 ⁰ C, which is 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.

Preparation 6 2-Amino-5-phenyl-6-methyIp yraζ in

This intermediate pyrazine is prepared by a stepwise process.

In the first stage, a mixture of 6.5 g of 1-phenyi-1,2-propanedione-2-oxime (commercially available) and 10 g of 1 g of aminomalonic acid are stirred.

Acid nitrilosylate in 60 ml of isopropyl alcohol overnight at room temperature. The reaction mixture is then filtered to give 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 the addition, 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. In this way, 1 g of 2-amino-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, mixed 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), further 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 1- (4-methoxyphenyl) -1,2-propanedione-2-oxime.

/ '

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

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

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

11. 2-Amino-5- (alpha, alpha, alpha-trifluoro-m-toiyl) -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-Amine-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-methyl-pyrazine of 1-cyclohexyl-1,2-propanedione-2-oxime.

17. 2-Amino-5- (4-methylthiophenyl) -6-methylpyrazine from 1- (4-methylthiophenyl) -1,2-propanedione-2-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, identified by their NMR and IR spectra:

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

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

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

22. 2-Amino-5- (p-toIyI) 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-Amino-5- (4-t-butylphenyl) pyrazine from 4-t-butylphenylglyoxaloxime.

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

Preparation 2 7 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) to give 1- (4-bromophenyl) -1,2-butanedione-2-oxime, which is identified by IR and NMR spectra.

In the second stage, the thus obtained 1- (4-bromophenyl) -1,2-butanedione-2-oxime is further reacted according to the general procedure described in Preparation 6 to give 2-amino-5- (4 -bromo-phenyl) -6-ethylpyrazine, 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 of pyrazine-2-carboxamideide, 85 ml of glacial acetic acid and 75 ml of 30 percent hydrogen peroxide is heated to about 55 ⁰ 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 umkrista.llisiert from hot water, whereby one arrives at 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.

213 69 ·

A mixture of 4 g of the pyrazine oxide obtained in the above manner in 40 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 stage of the process.

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 drying agent is filtered off and the solvent removed under vacuum to leave a solid which, due to its IR spectrum, is 2-amino-6-cyanopyrazine. This material is used without further purification for the preparation of compounds of formula I.

Production 2 9

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

Do this 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).

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 resulting solution is cooled and added tropfenv / ice 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 one arrives at 3,6 g of a product according order - * - crystallization from a mixture of benzene and hexane at about 133 to 136 ⁰ C melts. Based on an NMR spectrum and elemental analysis, this product is 2-amino-6-trifluoromethylpyrazine.

Analysis for C ₅ H ₄ F ₃ N ₃ ;

calculated found

C 36.82% • H 2.47 N. 25.76

Preparation 3 O 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 i.n 140 ml of aqueous 60 percent sulfuric acid and et v / a 8 hours heated to about 135 ° C. 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 one reaches 2.2 g of a product, which melts at about 118 to 122 ° C. This product is 2-amino-5-trifluoromethylpyrazine based on NMR spectrum and elemental analysis.

Analysis for C ₅ H ₄ F ₃ N ₃ :

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-propanedione 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 stirring 2 g of aminoacetarrtidine dihydrobromide, with further stirring then 8.6 ml of aqueous 2N sodium hydroxide was 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

- 27 - äf 3 690

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 an eluent. In this way one reaches 100 mg of material, which is 2-amino-5-phenyl-6-trifluoromethylpyrazine.

Production 32

-S- (4-bromophenyl) -6-chloropyrazine This compound is prepared stepwise. step 1

A mixture of 37 g of 1- (4-bromophenyl) -1,2-propanedione-2-oxime, 34% 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. Subsequently, the reaction mixture is mixed with a further 3 g of the tosylate salt and stirred for several more days at room temperature. 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

- 28 - 21 3 69

filtered off. In this way one arrives at a melting at about to 205 ° material, which is due to its NMR spectrum to '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 to reflux temperature, whereupon the excess Phosphorox'ychlorid removed under vacuum. The residue is very carefully mixed with ice, after which 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) methylene / -iminoipyrazin. The yield is 10.5 g.

level 3

A mixture of 12 g of 5- (4-bromophenyl) -S-carbethoxy-6-chloro -, / (dimethylamino) methylene / imino ^ pyraζin (prepared according to Step 2) and 150 ml of aqueous 2N hydrochloric acid is added with stirring Heated to reflux for 5 minutes, giving a white precipitate. The mixture is cooled and treated with about 50 ml of aqueous 1N sodium hydroxide solution. The mixture is filtered off,

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 10 g.

Analysis for C.-EL .. BrClN-O ,,

calculated found

C 43,79 H 3,11 N 11,78

43 , 90% 3 , 33 11 , 59

Level 4

A mixture of 10 g of 2-amino-5- (4-bromophenyl) -3-carbethoxy-6-chloropyrazine, 75 ml of dioxane, 75 ml of water and 8 g of sodium hydroxide pellets is heated briefly to reflux, dissolving everything. 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 21% : ₇ BrCl 15 C calculated 79 H 40 N 2, 12

found

40.10%

2.23 12.63

Level 5

A mixture of 9 g of 2-amino-5- (4-bromophenyl) -3-carboxy-öchlorpyrazin and 50 ml of tetralin is heated for about 15 minutes at reflux temperature. 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 I

1- (2-chlorobenzoyl) -3- / 5- (4-bromophenyl) -6-methyl-2-pyraziny] 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 elemental analysis and the NMR and IR spectra, these are 1- (2-chlorobenzoyl) -3- / 5- (4-bromophenyl) -6-methyl-2-pyrazinyl / urea f.

Analysis for C ₁₉ H.

calculated found

C 51.20% 51.03%

H 3,17 3,37

N 12.57 12.62

_ ₃₁ _ 113 69

Using the general procedure outlined in Example 1 ', the following further compounds are prepared using appropriate starting materials, which are identified by elemental analysis, NMR spectrum and IR spectrum:

1A. 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.

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

IC. 1- (2-bromobenzoyl) -3- / 5- (4-bromophenyl) -6-methyl-2-pyrazinyJL / harnstof f having a melting point of about 220-222 ⁰ C, starting from 2.0 g of 2-Aminc- 5- (4-bromophenyl) -6-methylpyrazine and 2.0 g of 2-bromobenzoyl isocyanate.

1D. 1- / 5- (4-bromophenyl) -e-methyl ^ -pyrazinyiy-S- (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

1E. 1- (2-chlorobenzoyl) -3- / 5- (4-ethylphenyl) -6-methyl-2-pyrazinyJL / 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.

IF. 1- (2-chlorobenzoyl) -3- (C-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 -Chlorberlzoylisocy3nat.

^ G. 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-amino-6-trifluormethylpyrazin and 1.6 g 2 -Chlorbenzoylisocyanat.

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

Tl. 1- (2-chlorobenzoyl) -3- / 5- (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.

1.j. 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.

1: Κ. 1- (2-bromobenzoyl) -3- (5-trifluoromethyl-2-pyrazinyl) urea having a melting point of about 206 to 208 ⁰ C, starting from 3OO mg of 2-amino-5-trifluoromethylpyrazine and 500 mg of 2-bromobenzoyiisocyanate.

1 L. 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 from 0.9 g of 2-amino-5- (4-bromophenyl) -6-chloropyrazine and 0.65 g of 2-chlorobenzoyl isocyanate.

_ ο ο _ ^{% äSa} - B VP τ * * *% #

Example 2 1- (2-Chlorobenzoyl) -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 extracted twice from a mixture of ethyl

_{ - acetate and a small amount of dimethylformamide recrystalli- "ν

sxert to give 200 mg of product, which melts at about 231 to 234 ⁰ C. This product is 1- (2-chlorobenzoyl) -3- / 5- (4-chlorophenyl) -2-pyrazinyl / harnsfcoff based on elemental analysis and NMR spectrum.

analysis for C ₁₈ H ₁₆ Cl ₂ NO ι 4 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 2 above and using appropriate starting materials, the following further compounds are prepared, which are identified by elemental analysis and NMR spectra:

2A. 1- (2-chlorobenzoyl) -3- / 6-methyl-5- (alpha, alpha, alpha-trifluoro-m-tolyl) -2-pyrazinyl / Haristof f having a melting point of about 202 to 204 ⁰ C in one Amount of 0.95 g, starting from 1.0 g of 2-amino-5- (alpha, alha, alpha-trifluoromotolyl) -6-methylpyrazine and 1.3 g of 2-chlorobenzoyl isocyanate.

2 B. 1- (2-chlorobenzoyl) -3- / 5- (4-methoxyphenyl) -6-methyl-2-pyraziny ^ / 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.

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

2 D. 1- (2-Methylbenzoyl) -3- / 6-methyl-5- (alpha, alpha, alpha-trifluoro-m-tolyl) -2-pyrazine-3-vinylurea having a melting point of about 211 to 212 g in an amount of 30:30 mg, starting from O, 5 g of 2-amino-5- (alpha, alpha, alpha-tifluoro-m-tolyl) -6-methylpyrazine and 0.75 g of 2-methylbenzoyl isocyanate.

2E. 1- / 5- (4-methoxyphenyl) -6-methyl-2-pyrazinyl _ / - 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.

2F. 1 - (2-chlorobenzoyl) -S - ^ -methyl-S- (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 2-Amino-6-methyl-5- (4-methylphenyl) pyrazine and 0.8 g of 2-chloro benzoyl isocyanate.

2g. 1- / 5- (4-bromophenyl) -2-pyrazinyl] - / 3- (2-chlorobenzoyl) urea having a melting point of about 227 to 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.

213 690

2H. 1- / 5- (4-bromophenyl) -6-ethyl-2-pyrazinyl / -3- (2-chlorbenzoyD'iiarnstoff having a melting point of about 208-210 ⁰ C in an amount of 270 mg, starting from 0,6 g 2-Amino-5- (4-bromophenyl) -6-ethylpyrazine and 1.0 g of 2-chlorobenzoyl isocyanate.

2i. 1- (2-chlorobenzoyl) ^ - / e-methyl-S- (4-phenoxyphenyl) -2-pyrazinyl] L / 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 2-chlorobenzoyl isocyanate.

2J. 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-biphenylyl) pyrazine and 0.7 g of 2-chlorobenzoyl isocyanate.

2K. 1- (2-chlorobenzoyl) -3- / 5- (4-fluorophenyl) ~ 6-methyl-2-pyrazine-1-diol / 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-fluorophenyl) -6-methylpyrazine and 0.6 g of 2-chlorobenzoyl isocyanate.

2L. 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 ° C, starting from 0.5 g 2-amino-5- (4-fluorophenyl) pyrazine and 0.5 g of 2-chlorobenzoyl isocyanate.

2M. 1- (2-chlorobenzoyl) -3- / 5- (alpha, alpha, alpha-trifluoro-p-tolyl) -2-pyrazine-1-yl / urea f 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.

Example 3

1- / 5- (3-bromophenyl) -6-methyl-2-pyrazinyl-3-methyl-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 for C ₁ "EL -BrClN.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 3 and using appropriate starting materials, the following further compounds are prepared, which are identified by elemental analysis and NMR spectra:

3 A. 1- (2-chlorobenzoyl) -3- (5-cyclohexyl-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 of 2-amino-5-cyclohexyl-6-methylpyrazine and 0.63 g of 2-chlorobenzoyl isocyanate.

'213

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

3 C. 1- (2-chlorobenzoyl) -3- / 6-methyl-5- (2-tolyl) -2-pyrazinyl./-harnstoff in an amount of 0.22 g with a melting point of about 206-207 ⁰ C, starting from 0.35 g of 2-amino-6-methyl-5- (2-tolyl) pyrazine and 0.4 g of 2-chlorobenzoyl isocyanate.

The compounds of formula II are useful for controlling insects of various orders including Coleoptera such as spotted ladybug, cotton boll weevil, corn root beetle, cereal beetle, ground fleas, borers, coioro potato beetle, corn beetle, alfalfa beetle, carpet beetle, meal beetle, beetle beetle, wireworm worm, rice beetle, roseweed beetle, Pruning shears or white larvae of hornbeam beetles, diptera, v / ie house fly, yellow fever mosquito, stable fly, horn fly, blowfly, larva of cabbage fly or carrot fly, lepidoptera, such as cotton moth caterpillar, codling moth, owl caterpillar, clothes moth, cornmeal moth, curler larva, corn beetle larva, corn borer Large cabbage white larvae, cabbage vines, cotton boll larva larva, sac carrier caterpillar, eastern tent caterpillar, grasshopper 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 I in which

A ^{1 is} bromine or chlorine,

R is hydrogen, trifluoromethyl or

is

R, 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 I 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- (monoo-substituted-benzoyl) -3- (substituted pyrazinyl) urea s of the formula I treated.

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

For the formulation of corresponding insecticidal agents from the novel compounds of the formula I, the respective active ingredient is either mixed with a solid carrier or dissolved or dispersed in a liquid carrier. If desired, adjuvants such as surfactants and stabilizers may also be included in 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, about 10 to 80 parts by weight of a solid inert carrier, for example a carrier of the abovementioned type, is mixed 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 an alkylnaphthalenesulfonate, and preferably also with about 0.5 to 5 parts by weight of a wetting agent, 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, polyoxyethylenesorboxylic 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 the formula I. Of course, other pesticidal compounds may also be included. In this way, the spectrum of activity of such formulations can be broadened.

The amount of 1- (mono-o-substituted-benzoyl-3- (substituted-pyrazinyl) urea 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 surface of the strength of infestation by insects, the condition of the treated foliage and the temperature or humidity to be treated vegetative. in general, the application of the active ingredient is recommended in a formulation containing an active ingredient concentration of from about O ₁ .1 to 1000 ppm contains.

The insecticidal activity of novel compounds of the research '(! Mel I was examined by an examination of appropriate formulations of caterpillars spotted ladybird (Epilachna varivesta) and (to caterpillars of the cotton moth southern armyworm). 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 rates of use 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 nourished.

_ ₄₂ _

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 manifestation (Epilachna varivestis) and 5 larvae of the caterpillar dex cotton moth from the second

13-690

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 dishes are then placed in a conditioning room for a further 3 days with the temperature and humidity conditions given above, followed by the appropriate assessment at the end of the seventh day. The percentage control of the insects is determined by counting the number of living larvae determined 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 two insects mentioned there for the different active substance concentrations, namely for the application quantities of 1000 ppm and of 100 ppm.

_ 44 -

T a b e 1 1 e I

Connection ppm 4. Day 7. ma- Caterpillar of the tree woolly moth 7th day appraisal values i 1000 1 Day 4th day 3 Mission-spotted lot 'ladybug I. 100 1 3 3 3 1 A 1000 1 2 3 2 100 1 2 2 1 IB 1000 0 1 ' 1 2 100 0 0 1 1 rc 1000 0 0 0 3 100 0 3 3 3 1, D 1000 0 2 3 3 100 0 1 3 3 VE 1000 0 0 3 3 100 0 2 3 3 ! 1 F 1000 1 3 3 2 100 0 2 2 0 1 .G 1000 0 1 0 2 100 0 3 2 0 1 ΪΗ 1000 0 2 0 .0 100 0 0 1 0 TI 1000 0 0 0 3 100 0 2 3 3 U 1000 0 1 3 3 100 0 1 3 2 U IQOO 2 0 2 2 O 2 2 2 2 2

- 45 -

T h e 1 1 e I (continued)

Assessment Values Mission-spotted Maize Caterpillar

amount rien beetle 7th day 4th wanted moth Verbin 2 3 dung ppm 4th day 0 3 Day 7th day IL 1000 0 0 3 3 100 0 0. 3 3 2 1000 0 3 2 3 100 0 2 2 3 2 B 1000 2 0 r-t 3 100 1 C C 3 2C 1000 0 2 3 1 100 0 1 3 0 2D 1000 1 1 . .3 3 100 0 0 2 3 2 E 1000 0 3 2 Third 100 0 3 2 3 2-F 100.0 2 0 3 3 100 2 0 2 2 2G 1000 0 0 2 3 100 0 0 0 3 2 H 1000 0 2 2 3 100 0 2 1 1 2 · I 1000 2 1 3 2 100 1 0 0 1 2 y 1000th 0 3 100 0 1

Table I (port setting) assessment values

Mission-spotted macaw caterpillar of tree trunk beetle woolly moth

Connection ppm 4th Day 7th day 4th day 7th day - 3 1000 O .3 3 3 100 0 1 2. 2 , 13 "A 1000 100 1 0 NJ U) U) U) 3 3 1000 1 3 2 3 100 0 1 0 2

-47 - S! 3 6

Trial 2

Several of the new compounds of formula I 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 living larvae of caterpillars of the tree moth (Spodoptera eridania) per Petri dish and then using the values obtained from them according to the formula of Abbott / W. W. Abott, "A Method of Computing the Effectiveness of an Insecticide," J. Econ. Entomol. 18, 265-267 (19252./), the percentage control is as follows:

Number of surviving animals at the controls.

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

Control number of surviving animals in the control

The results obtained in the above tests are shown in the following Table II. Test results based on raeh.3 as an experiment are indicated by means.

Table II

Order percentage control

amount . Cotton moth caterpillar compound in ppm Day 4 Day 7

1C1D

100 100 100 50 100 100 25 100 100 10 95 100 5th 57 96 2.5 54 93 I ₇ O 17. 76 0.5 0 20 100. 100 100 50 100 100 25 100 100 10 100 100 5 100 100 2.5 , 100 100 1.0 60 93 0.5 20 73 100 100 100 50 100 100 25 100 100 10 100 100 5 100 100 2.5   100 100 1.0 33 67 0.5 7 27

Table II (cont'd)

connection in ppm 1 E 100 50 25 10 5 2.5 1 I 100 50 25 10 5 2.5 1.0 0.5 1: L 10 5 2 100 50 25 10 5 2.5

Percentage of application rate Caterpillar of Bsumwol! Moth 4th day 7th day

1.0 0.5

100 100 100 100 100 10 0 81 93 80 100 27 47 100 100 100 100 100 100 100 100 96 100 80 100 20 73 0 53 100 100 13 75 100 100 93 100 93 100 57 100 30 76 13 27 0 0 7 7

- 50 - 11 3 6VU cotton moth T a b e 1 le II (Continuation) 7th day Assignment- percentage control 100 amount Caterpillar aer 100 Compound in ppm 4th day 100 2 A 100 100 100 50 100 100 25 100 100 10 .. 100 80 5 100 40 2.5 93 100 1.0 20 100 0.5 23 93 2 B . 100 93 73 50 100 100 25 86 100 10   27 100 2D. 100 100 100 50 100 100 25 100 100 10 100 100 5 100 100 ² > ⁵ 100 100 1.0 53 100 2E 100 100 100 50 100 73 25 100 10 86 5 27

f 13

T a 'b e 1 1 e II (cont'd)

Order percentage control

Amount of ' caterpillar of cotton moth compound ' in 'ppm ' 4th day 7th day

2.5

1.0

2F 100 50 25 10

2G 100

50 25 10

2-K 10

.3 A 10

27 47 20 27 100 100 87 93 93 100 67 93   100 100 93 100 100 100 80 100 100 100 20 73 67 100 0 27

Trial 3

falls

One of the compounds under the general formula Γ was also 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 1 100 90 1ST FLOOR 75 80 100 50 90 100 25 70

213 69

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 in 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 I 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

.54 XI Jl · O?

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

The sprayed leaves are placed in petri dishes containing caterpillar larvae of cotton moths of the second and third species (Spodoptera eridania), and the new leaves are placed in separate petri dishes, which also contain larvae from the second and third caterpillar caterpillar caterpillars , 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 Table V below.

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.

43 »

Tab e 1 le V

Assignment- percentage the BA fight New amount Caterpillar' umwo11motte 100 In ppm • 4th day New 94 connection 1000 'sprayed 73 28 j 1, 100 100 22 7th day 94 , 10 1 100 0 sprayed 89 1000 29 94 100 22 rc 100th 100 55 ' 100 100 10 100 0 88 83 1000 47 73 100 22 • ID 100 100 17 100 10 100 0 100 23 100 100 88

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

Trial 5

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

To formulate each active ingredient is dissolved in each case 10 mg of the test compound in 1 ml of acetone and then mixed this solution with 99 ml of water, so that a test 'solution results in an active ingredient concentration of 100 ppm. From this solution with an active ingredient concentration of 100 ppm, the required test solutions with lower active substance concentrations are then formed by serial dilution with water. Each 40 ml of the test solutions obtained thereby are added

in each case either in 100 ml glass beakers or in 160 ml plastic 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 rag of 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 Killing of yellow fever mosquito larvae

Compound order amount in ppm percentage mortality

I 0.01 100 IC 0.01 100

II 0.01 100 solvent - 0 untreated - 0

f 13 6

Trial 6

By this experiment, the ovicidal activity of several compounds of formula I is determined, using egg clusters of caterpillars of the cotton moth (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). Then the eggs in the Petri dishes are incubated until the untreated controls hatched. At this point, the number of eggs that have been excluded 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 figure of their preparation example, while column 2 shows the order amount in parts per million, (ppm) and in column 3 the values for percent kill are indicated.

table

VJI

Assignment Percent killing of eggs connection amount in ppm Cotton mary moth beetle 1 1000 100 500 100 250 100 100 100 50 100 I "! C 1000 100 500 100 250 100 100 100 TF 1000 100 1G 1000 100 1000 100 500 100 250 100 100 100 U 1000 100 1 κ 1000 100 500 100 250 100 100 100 50 100 2A 1000 100 500 100 250 100th 100 100

table

VII

(Continuation) Percent killing of eggs Lady bug Assignment Cotton moth connection amount in ppm 100   2 B 1000 100 500 95 250 100 100 100 100 2J 1000 10Ό 96 2K 10:00 100 96 500 100 250 100 100 100 50 100 25 96 10 100 5 100 3 1000

The experimental results show that the novel compounds of formula I are effective against a number of insects in the larval state, as the insects ingest 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 the formula I 'are also suitable as ovicidal agents.

Claims (1)

CLAIM THE INVENTION An insecticidal composition of a suitable inert carrier and an active ingredient in an insecticidally effective amount, characterized in that it contains as active ingredient an A- (mono-o-substituted-berizoyl) -3- (substituted-pyrazinyl) urea of the formula I. .O θ _χ "j, I j | · (I) .; ¹ Ü ^VN ' H H contains, in which A 'is bromine, chlorine or methyl, R is hydrogen, halogen, C_-C _g -cycloalky, halo (C ₁ -C.) Alkyl, nitro, cyano, q ^ ⁰ - ⁰ ^ xq or naphthyl, R 4 represents hydrogen, halogen, methyl, ethyl, cyano or halo (C ₁ -C ₂ ) alkyl, with the proviso that the substituents R and R can not be hydrogen at the same time, - 61 - & ί ύ R is hydrogen, halogen. Halogen (C - C.) Alkyl C ₁ -C ₄ alkylsulfonyl, nitro, cyano, phenoxy or phenyl, q is 0, 1, 2 or 3, ρ is 0 or 1 and X ^{1 is} O O 11 II , -0-, -S-, -S- or -S- Il stands.