KR960010344B1 - Substituted 2,4-diamino-5-cyanopyrimidines and the preparation therefor - Google Patents

Abstract

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Description

Substituted 2,4-diamino-5-cyanopyrimidine and process for preparing these compounds

The present invention relates to novel substituted 2,4-diamino-5-cyanopyrimidines and their salts and the middle ages, the preparation of these compounds and the use of the compounds for controlling pests and external parasites.

This novel compound is a compound of formula (I):

또는 -NH-CH=N-R₁₀으로 구성된 군으로부터 선정된 라디칼이고 ; R₅는 수소, C₁-C₁₂알킬, C₃-C₆시클로알킬, C₁-C₆알콕시, 과할로겐화 C₁-C₃알킬 또는

라디칼이고 ; R₆는 C₁-C₆알킬이며 ; R₇은 수소 또는 C₁-C₆알킬이고 ; R₈및 R₉는 각각 독립적으로 수소 또는 C₁-C₆알킬이거나 또는, R₈및 R₉를 합쳐서 -(CH₂)₃-, -(CH₂)₄- 및 -(CH₂)₅로 구성된 군으로부터 선정된 라디칼이며 ; R₁₀은 -SO₂-R₁₃라디칼 또는

라디칼이고 ; R₁₁및 R₁₂는 각각 독립적으로 수소 또는 C₁-C₆알킬이거나 또는, R₁₁및 R₁₂를 합쳐서 -(CH₂)₃-, -(CH₂)₄- 및 -(CH₂)₅로 구성된 군으로부터 선택된 라디칼이며 ; R₁₃은 C₁-C₁₀알킬, 10개까지의 할로겐원자로 치환된 C₁-C₁₀알킬, 또는 C₃-C₆시클로알킬이고 ; R₁₄및 R₁₅는 각각 독립적으로 C₁-C₁₀알킬이고, 또 X 및 Y는 각각 독립적으로 산소 또는 유황이다.Wherein R ₁ is hydrogen, C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl or C ₂ -C ₆ alkynyl, and R ₂ is hydrogen, C ₁ -C ₁₀ alkyl or C ₃ -C ₆ cyclo Alkyl or a radical selected from the group consisting of — (CH ₂ ) ₃ —, — (CH ₂ ) ₄ and — (CH ₂ ) ₅ ) in combination of R ₁ and R ₂ ; R ₃ is hydrogen or a —CO—R ₅ or —SO ₂ —R ₆ radical; R ₄ is -NH ₂ , -NH-CO-R ₅ , -NH-SO ₂ -R ₆ ,

Or a radical selected from the group consisting of —NH—CH═NR ₁₀ ; R ₅ is hydrogen, C ₁ -C ₁₂ alkyl, C ₃ -C ₆ cycloalkyl, C ₁ -C ₆ alkoxy, perhalogenated C ₁ -C ₃ alkyl or

Radical; R ₆ is C ₁ -C ₆ alkyl; R ₇ is hydrogen or C ₁ -C ₆ alkyl; R ₈ and R ₉ are each independently hydrogen or C ₁ -C ₆ alkyl, or R ₈ and R ₉ combine to-(CH ₂ ) ₃ -,-(CH ₂ ) ₄ -and-(CH ₂ ) ₅ ; A radical selected from the group consisting of; R ₁₀ is a -SO ₂ -R ₁₃ radical or

Radical; R ₁₁ and R ₁₂ are each independently hydrogen or C ₁ -C ₆ alkyl, or R ₁₁ and R ₁₂ combine to-(CH ₂ ) ₃ -,-(CH ₂ ) ₄ -and-(CH ₂ ) ₅ ; A radical selected from the group consisting of; R ₁₃ is C ₁ -C ₁₀ alkyl, up to 10 halogen atoms C ₁ -C ₁₀ alkyl, or C ₃ -C ₆ cycloalkyl; R ₁₄ and R ₁₅ are each independently C ₁ -C ₁₀ alkyl, and X and Y are each independently oxygen or sulfur.

Within the scope of the present invention, halogen atoms and halogen substituents mean fluorine, chlorine, bromine or iodine, with fluorine and chlorine being preferred.

Because of the advantageous properties, preferred compounds of formula (I) are those in which R ₁ is hydrogen or C ₁ -C ₄ alkyl and R ₂ is C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl, or R ₁ and R ₂ together are — (CH ₂ ) ₄ — or — (CH ₂ ) ₅ — radical, R ₃ is hydrogen, R ₄ is —NH ₂ or —NH—CO—R ₅ radical, and R ₅ is C _1- Compounds and salts thereof as well as C ₄ alkyl or perhalogenated C ₁ -C ₃ alkyl, R ₁ is hydrogen, methyl or ethyl, R ₂ is C ₁ -C ₄ alkyl or cyclopropyl, R ₃ is hydrogen, General formula (I) compounds and salts thereof, wherein R ₄ is a -NH ₂ or -NH-CO-R ₅ radical and R ₅ is C ₁ -C ₃ alkyl.

Because of excellent pesticide activity, particularly preferred compounds of formula (I) are those in which R ₁ is hydrogen, methyl or ethyl, R ₂ is cyclopropyl, R ₃ is hydrogen, and R ₄ is —NH ₂ or —NH-CO -C ₂ H ₅ radicals, and salts thereof.

Salts of the compounds of formula (I) mean physiologically acceptable addition salts of inorganic or organic acids. Examples of the non-acid include hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, phosphoric acid, phosphorous acid and nitric acid.

Examples of organic acids include trifluoroacetic acid, trichloroacetic acid, formic acid, oxalic acid, succinic acid, maleic acid, lactic acid, glycolic acid, aconitic acid, citric acid, benzoic acid, benzenesulfonic acid and methanesulfonic acid.

또는 -NH-CH=N-R₁₀인 일반식(I) 화합물로 전환시키고 또, 필요한 경우, 생성한 일반식(I) 화합물을 그의 염으로 전환시키는 것에 의해 제조할 수 있다.The compound of formula (I) may be reacted by a) reacting a compound of formula (II) with ammonia, or b) reacting a compound of formula (III) with an amine of a compound of formula (IV) In this case, the resultant general formula (I) compound (Compound Ia), wherein R ₃ is hydrogen and R ₄ is -NH ₂ radical, is known in a known manner, wherein R ₃ is -CO-R ₅ or -SO ₂ -R ₆ And / or R ₄ is -NH-CO-R ₅ , -NH-SO ₂ -R ₆ ,

Or by converting to the general formula (I) compound having -NH-CH = NR ₁₀ and converting the generated general formula (I) compound to a salt thereof, if necessary.

Wherein R ₁ to R ₁₅ , X and Y are as defined above and n is 0.1 or 2.

In the preparation a), the reaction of the sulfonyl compound (n = 2) of the general formula (II) with ammonia is generally carried out in an organic solvent such as acetonitrile, tetrahydrofuran, dioxane or Run in a solvent / water mixture. The same reaction conditions can be applied to preparation b) in which 2-chloro-4,6-diamino-5-cynopyrimidine of formula (III) is reacted with formula (IV) amine. When methylthio compound (n = 0) is used as starting material in preparation a), the reaction with ammonia is preferably autoclave at a temperature range of 100 ° to 170 ° C., usually at about 160 ° C., under elevated pressure. Run inside

The conversion of a compound of formula (I) wherein R ₄ is —NH ₂ to a compound of which R ₄ has the other meanings referred to herein is the reaction of the amino group at the 6-position of the pyrimidine ring with a suitable known reactant already known. It can carry out by. Thus, for example, 6-aminopyrimidine of formula (I) may be selected from Hal-CO-R ₅ , wherein Hal is a halogen atom, preferably a chlorine atom, and R ₅ , R ₆ and R ₁₀ have a given meaning; Reaction with a compound of the type Hal-SO ₂ -R ₆ , (R ₅ -CO) ₂ O or R ₆ O-CH = NR ₁₀ yields a compound of general formula (I) which is suitably substituted in the 6-position.

라디칼인 일반식(I) 화합물을 제조해야 하는 경우, 6-NH₂기를 일반식

의 아세탈과 반응시키며, 여기서 R₆,R₇,R₈및 R₉는 주어진 의미를 갖는다. 유사 제법 및 적당한 반응물을 사용하여 R₃이 수소인 일반식(I)의 4-아미노피리미딘으로부터 R₃가 -CO-R₅또는 -SO₂-R₆라디칼인 일반식(I) 화합물을 제조할 수 있다.R ₄ is

If it is necessary to prepare a compound of formula (I) which is a radical, the 6-NH ₂ group

Reacts with an acetal of where R ₆ , R ₇ , R ₈ and R ₉ have the meaning given. Analogous formulations and suitable reactants give the general formula (I) compounds wherein R ₃ is —CO—R ₅ or —SO ₂ —R ₆ radicals from 4-aminopyrimidines of formula (I), wherein R ₃ is hydrogen. can do.

The acylation reactions described above can be carried out in an inert solvent or diluent at temperatures ranging from 0 ° to 120 ° C., preferably from 40 ° to 80 ° C., at atmospheric pressure in the presence of a base and at atmospheric pressure. Examples of suitable solvents and diluents include alkanes such as their agonists, including isomers up to n-heptane and n-heptadencane; Ethers such as diethyl ether, dipropyl ether, dibutyl ether, dimethoxyethane, dioxane or tetrahydrofuran; Chlorinated hydrocarbons such as chloroform, methylene chloride, carbon tetrachloride or chlorobenzene; Aromatic hydrocarbons such as benzene, toluene or xylene. Other inert solvents and diluents may also be suitably used in the preparation of the present invention. Bases which may suitably be used in the reaction include, for example, alkylamines such as triethylamine or diisopropyl ethylamine and pyridine or N-methylpyrrolidone.

Starting compounds of the general formula (II) are novel, and in particular, these compounds have excellent pesticide properties, in particular pesticidal properties, and constitute the object of the present invention. These compounds can be prepared as follows:

a) For example, a compound of formula (II) wherein n is 0 can be prepared according to the following scheme:

Formula (VI) salts prepared by reaction with dimethyl N-cyanodithiocarboxyimidate and malonitrile of formula (V) used as starting materials in the above preparation are known (eg Rec. Trav. Ch. 90/1971, 463; J. Chem. Comm. 1974, 350). A general formula (II) compound with n = 0 is obtained by cyclizing the alvinyl (VI) salt with 5N HCl and then reacting the resulting general formula (VI) pyrimidine with the corresponding general formula (IV) amine. Can be.

b) In addition, a compound of formula (II) wherein n is 0 can be obtained as follows:

The sodium salt of general formula (VIII), the urea of general formula (IX) and the uracil of general formula (X) shown in the scheme above are known (e.g. J. Chem. Soc., Chem. Comm. 1974, 350 Helv, Chim. Act. 1985, 1155). The preparation of novel substituted pyrimidines of formulas (XI) and (XII) can be carried out by known methods. The reaction of general formula (XII) with ammonia yields a general formula (IVV) compound where n is zero.

c) can be prepared by the known methods for oxidizing compounds of formula (II), wherein n is 0, which is the starting compound of formula (II), wherein n is 1 or 2 (eg, The Chemistry of Heterocyclic Compounds, Vol. 16: Pyrimidines, Intersc.Publ. Inc. NY1959). Starting compounds of the general formula (III) such as, for example, 2-chloro-4,6-dianimo-5-cyanopyrimidine can be prepared from Chem. Ber. 1968, would known in 1244, by oxidation of the formula (VII) compound to produce a sulfone, and also ammonia and the reaction can be produced according to the following reaction scheme to replace the -SO ₂ CH ₃ -NH ₂ with:

2,4,6-triamino-5-nitropyrimidine pesticides, in particular pesticides, which are amino groups which may be substituted, are already known from EP 0084,758. The compounds of formulas (I) and (II) are structurally different from known compound materials in containing cyano groups in the 5-position.

Surprisingly, it has been found that the compounds of formulas (I) and (II) and salts thereof have excellent pesticide properties that are acceptable by plants and low toxicity to warm-blooded animals. They are particularly suitable for the control of pests and representative pests of the species Aarina, which invade plants and animals.

In particular, the general formula (I) and (II) compounds are Lepidoptera, Coleoptera, Homoptera, Hepoptera, Diptera, Tisantoptera (Thysanoptera), Orthoptera, Anoplura, Siphonaptera, Silomapta, Mallophaga, Thysanura, Isoptera, Psocoptera And pests of the tree Hymenoptera; And a representative pest control of Acarina tree with Ixodidae, Argasidae, Tetranychidae and Deermanysaidae.

In addition to acting on maritime and mosquito larvae, such as, for example, Musca domestica, the compounds of the present invention can be used for ornamental plants and useful crops, especially cotton (e.g., Spodoptera littoralis and Heliotis viresense). ) And fruit and vegetables (e.g., flutella xylostelma, Lasperesia pomonella, leptinotarsa desemrineata, and epirakna baribestis) are also suitable for controlling plant erosion pests. . Compounds of formulas (I) and (II) are also effective against rice pests. The compounds of formulas (I) and (II) also have a significant scattering action and in particular larval eradication against pests, in particular larvae of harmful eroding pests. When adult insect pests ingest the active compound with food, it can be observed that spawning and / or hatching rates are reduced in many pests, especially choloteera such as, for example, Antonomus grandis.

Compounds of formulas (I) and (II) are used for the control of external parasites such as Lucilia sericata in livestock and productive livestock, for example by treating animals, cowsheds, barn stalls, etc. May also be used.

When herbivores are treated with the compounds of the present invention, such as, for example, by wet dips, pours, or spray races, the surprising adhesion of the active ingredient is an example of the skin and fur of the animal. For example, it provides a lasting toxic effect on external parasites such as harmful diphthera. This prevents the active ingredient administered to the skin or hair of a productive livestock from being washed away too quickly by rainwater loaded on the animal.

A particular advantage of the compounds of the invention is that they can be spherically dosed to productive livestock. In this method of administration, the active ingredient exhibits effective and sustained pesticidal activity, especially in the excretion secreted from the digestive tract.

Thus, the diphtheria larvae hatched from the deposited eggs are immediately killed, which makes it possible to control infections by harmful pests such as diphtheria, for example, before pests occur in the vicinity of animals such as barns, fences and pastures. A particularly important aspect of this particular dosage form is that the compound of formula (I) is physiologically harmless to warm animals because of its structural properties. This method of selectively controlling the spread of pests is more effective and at the same time more economical than conventional methods of large-scale treatment of barns and fences.

Good pesticide activity of the compounds of formulas (I) and (II) corresponds to a mortality of at least 50-60% against the pests.

The activity of the compounds of the present invention and compositions containing them is substantially extended by the addition of other insecticides and / or tick repellents and applied to the surrounding environment. Examples of suitable additives include organophosphate compounds, nitrophenols and derivatives thereof, formamidine, urea, carbamate, pyrethroids, chlorinated hydrocarbons, and Bacillus serringiencises.

The compounds of the present invention are used in the form of prototypical or preferably adjuvant commonly used in formulation technology, and also known methods include emulsifiable concentrates, direct sprayable or dilutable solutions, diluents, wettable powders, water solubles, It is formulated with a propellant, a granule, and a capsulant, for example in a polymeric material. Along with the nature of the composition, the method of administration, such as spraying, atomizing, spraying, spraying or pouring, is selected according to the intended purpose and the surrounding environment.

Formulations, for example compositions, formulations or mixtures, containing a combination of formula (I) or (II) compounds (active ingredient) and other pesticides or tick repellents and, if necessary, solid liquid auxiliaries, are for example active The components are prepared by known methods such as mixing and / or grinding uniformly with a solvent, a solid carrier and optionally a cooperative agent such as a surfactant compound (surfactant).

Suitable solvents include, for example, aromatic hydrocarbons containing preferably 8 to 12 carbon atoms, such as xylene mixtures or substituted naphthalenes; Phthalates such as dibutyl phthalate or dioctyl phthalate; Aliphatic hydrocarbons such as cyclohexane or paraffin; Alcohols and glycols such as ethanol, ethylene glycol, ethylene glycol mono methyl or mono ethyl ether and ethers and esters thereof; Ketones such as cyclohexanone; Strong polar solvents such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide; And vegetable oils such as epoxidized coconut oil or soy bean oil or epoxidized vegetable oils; Or water.

Solid carriers used in, for example, dusting agents and dispersible powders are natural mineral fillers such as calcite, talc, kaolin, montmorillonite or attapulgite. Highly disperse silicic acid or highly disperse absorbent polymers may also be added to improve physical properties. Suitable granular adsorptive carriers are for example porous, such as pumice, broken bricks, sepiolite or bentonite; Suitable non-absorbent carriers are also materials such as calcite or sand. In addition, many inorganic or organic glandular materials, for example dolomite or milled plant residues, can also be used.

Depending on the nature of the active ingredient to be formulated or its combination with other pesticides or mite repellents, suitable surfactant compounds are nonionic, cationic and / or anionic surfactants with good emulsifying, dispersing and wetting properties. The term surfactant is meant to encompass a mixture of surfactants.

Suitable anionic surfactants can be both water soluble soaps and water soluble synthetic surfactant compounds.

Suitable soaps are, for example, alkali metal salts of higher fatty acids (C ₁₀ -C ₂₂ ), alkalis such as sodium or potassium salts of oleic or stearic acid, sodium or potassium salts of natural fatty acid mixtures obtained from coconut or animal oils. Earth metal salts or unsubstituted or substituted ammonium salts.

More suitable surfactants are also modified and circular phospholipids with fatty acid methyltaurine salts.

Often, however, so-called synthetic surfactants are used, in particular fatty sulfonates, fatty sulfates, sulfonated benzimidazole derivatives or alkaline aryl sulfonates.

Fatty sulfonates or sulfates are usually in the form of alkali metal salts, alkaline earth metal salts or unsubstituted or substituted ammonium salts and contain C ₈ -C ₂₂ alkyl radicals comprising alkyl moieties of acyl radicals, for example lignosulfonic acid Sodium salt or calcium of the dodecyl sulfate, or fatty alcohol sulfate mixture obtained from the natural fatty phase. These compounds also include salts of sulfated and sulfonated fatty alcohol / ethylene oxide adducts. The sulfonated benzimidazole derivatives preferably contain one sulfonic acid group and one fatty acid radical containing 8 to 22 carbon atoms. Examples of alkylaryl sulfonates are dodecylbenzene sulfonic acid, dibutylnaphthalene sulfonic acid, or sodium salt, calcium salt or triethanol amine salt of naphthalene sulfonic acid and formaldehyde condensate.

Also suitable are the corresponding phosphates such as, for example, the phosphate ester salts of adducts of P-nonylphenol with ethylene oxide 4-14.

The nonionic surfactant is preferably an aliphatic or cycloaliphatic alcohol, or a polyglycol ether derivative of saturated or unsaturated fatty acids and alkylphenols, which (aliphatic) hydrocarbon residues contain 3 to 30 glycol ether groups and 8 to 20 The alkyl residues of the four carbon atoms and alkylphenols contain 6 to 18 carbon atoms.

More suitable nonionic surfactants are water soluble adducts of polyethylene oxide with polypropylene glycol, ethylene diamino polypropylene glycol and alkylpolypropylene glycols containing 1 to 10 carbon atoms in the alkyl chain, which adducts range from 20 to 250 Ethylene glycol ether groups and 10 to 100 propylene glycol ether groups.

These compounds usually contain 1 to 5 ethylene glycol units per propylene glycol unit.

Representative examples of nonionic surfactants include nonylphenolpolyethoxyethanol, castor oil polyglycol ether, polypropylene / polyethylene oxide adduct, tributylphenoxypolyethoxyethanol, polyethylene glycol and octyphenoloxypolyethoxyethanol Can be mentioned. For example, fatty acid esters of polyoxyethylene sorbitan, such as polyoxyethylene sorbitan trioleate, are also suitable as nonionic surfactants.

Cationic surfactants are preferably quaternary ammonium salts which contain one or more C ₈ -C ₂₂ alkyl radicals as N-substituents, unsubstituted or containing halogenated lower alkyl, benzyl or hydroxy-lower alkyl radicals as another substituent. . This salt is preferably in the form of a halide such as, for example, stearyltri methylammonium chloride or benzyldi (2-chloroethyl) ethylammonium bromide, methylsulfate or ethylsulfate.

Surfactants commonly used in the field of formulations include, for example, Mc Cutcheon's Detergents and Emulsifiers Annual, Mc Publishing Corp., Ridgewood, New Jersey, 1979; Dr. Helmut Stache, Tensid Taschenbuch (Handbook of Surfactants), Carl Hanser Verlag, Munich / Vienna 1981.

Agrochemical compositions usually comprise 0.1 to 99%, preferably 0.1 to 95%, active or 1 to 99.0% solids or liquid auxiliaries, 0 to 25% surfactants, or a combination of the active ingredient or another pesticide or tick insect repellent, Preferably it contains 0.1 to 20%.

Commercially available products are preferably formulated in concentrates, while the end consumer usually uses practically low concentrations of diluents.

The composition may also contain other ingredients such as stabilizers, antifoams, viscosity modifiers, binders, tackifiers, as well as fertilizers or other active ingredients to achieve special effects.

Example 1

a) Preparation of Starting Compound: 2-cyclopropylamino-4-amino-5-cyano-6-methylthiopyrimidine

i) While cooling with ice water, 650 ml of concentrated hydrochloric acid is added dropwise to a solution of 93 g of 2-cyano-3-cyano amino-3-methylthioacrylonitrile and sodium salt in 425 ml of water. The batch is then stirred for about 12 hours at room temperature. The precipitate is separated by filtration and treated with aqueous sodium carbonate solution. 20 g of the resulting 2-chloro-4-amino-5-cyano-6-methyltyropyrimidine (melting point 268 ° C.) was stirred in 250 ml of acetonitrile to prepare a suspension, and the mixture was stirred at reflux at vigorously. 11.4 g of cyclopropylamine is added dropwise. The batch is further stirred for 12 hours and then water is added. The precipitate is separated by filtration to give the title compound of the following general formula having a melting point of 215 ° 218 ° C. (Compound 3.1).

ii) 20 g of N, N-diethylaniline are slowly added dropwise to a mixture of 18.3 g of 5-cyano-6-methylthiouracil and 80 ml of phosphoroxy chloride. The batch is then refluxed for 1.5 hours and then concentrated by evaporation.

The residue is mixed with 200 ml of ice water, stirred, vertically filtered and washed with water. After drying, the crude product is chromatographed through a silica gel column (eluting with a 6: 1: 1 mixture of toluene / chloroform / ethyl acetate). 22 g of 2,4-dichloro-5-cyano-6-methylthiopyrimidine (melting point 118 ° -120 ° C) was dissolved in 200 ml of acetonitrile and 11.4 g of cyclopropylamine added to 40 ml of acetonitrile at -10 ° C. Add solution. The reaction mixture is stirred at room temperature for 2 hours and then poured into 2 liters of ice water. The precipitate is filtered by suction. Thus obtained 26.1 g of 2-cyclopropylamino-4-chloro-5-cyano-6-methylthiopyrimidine having the melting point of 139 ° -141 ° C is stirred in 100 ml of acetonitrile.

Then, 300 ml of 30% aqueous ammonia solution is added to the suspension, which is stirred at room temperature for about 10 hours and then at reflux for 5 hours.

The solid residue obtained from the cooled batch is filtered by suction and washed with water. Recrystallization from 150 ml of methyl cellosolve affords the title compound of the general formula indicated for i) having a melting point of 215 ° -218 ° C.

b) Preparation of 2-cyclopropylamino-4,6-diamino-5-cyanopyrimidy

33.7 g of 2-cyclopropylamino-4-amino-5-cyano-6-methylthiopyrimidine prepared according to a) is reacted with 150 g of ammonia for 15-20 hours in an autoclave at 150 ° C. The reaction product was repeatedly stirred in water and then separated by filtration to give the title compound of the following general formula having a melting point of 249 ° -251 ° C. (Compound No. 1.1).

Example 2

a) Preparation of the starting compound: 2-diethylamino-4-amino-5-cyano-6-methylsulfonylpyrimidine

Into the reaction vessel is charged 47.5 g of 2-diethylamino-4-amino-5-cyano-6-methylthiopyrimidine in 650 ml of methylene chloride. Without cooling, 88.7 g of 3-chloroperbenzoic acid is added to this batch.

The reaction mixture is stirred for 2 hours and then filtered. The filtrate is concentrated by evaporation and the residue is suspended in diethyl ether and filtered by suction to give the title compound of the general formula having a melting point of 170 ° -172 ° C. (Compound 3.2).

b) preparation of 2-dimethylamino-4,6-diamino-5-cyanopyrimidine

26.9 g of 2-diethylamino-4-amino-5-cyano-6-methylsulfonylpyrimidine prepared according to a) are added to 300 ml of a 30% aqueous ammonia solution and 100 ml of acetonitrile. This batch is then stored under reflux for 12 hours, cooled, and the precipitate is separated by filtration.

The precipitate is stirred in water and filtered by shock suction to give the title compound of the general formula having a melting point of 222 ° -224 ° C. (Compound 1.2).

Example 3

Preparation of 2-diethylamino-4-amino-5-cyano-6-isobutylaminophylimidine

7 g of triethylamine is added to a solution to which 10.3 of 2-diethylamino-4,6-diamino-5-cyanopyrimidine (prepared according to Example 2) 10.3 is added in 90 ml of tetrahydrofuran. 8.5 g of isobutyryl anhydride is then added dropwise to this solution at 60 ° C. The reaction mixture is heated at reflux for 48 hours, concentrated by evaporation and the residue is washed with diethyl ether to give the title compound of the general formula having a melting point of 151 ° -152 ° C. (Compound 1.3) .

Example 4

Preparation of N, N-dimethyl-N '-(2-cyanopropylamino-4-amino-5-cyanopyrimidin-6-yl) formamidine

3.7 g of dimethylformamide diethyl acetal was added dropwise to a solution added with 3.8 g of 2-cyclopropylamino-4,6-diamino-5-cyanopyrimidine in 100 ml of dioxane at 45 ° -50 ° C. The reaction mixture is stirred at 45-50 ° C. for 8 hours. The solvent is distilled off and the regeneration is recrystallized in ethanol to give the title compound of the following general formula having a melting point of 192 ° -195 ° C. (Compound 1.4).

Example 5

Preparation of starting compound: 2-Chloro-4,6-diamino-4-amino-5-cyano-6-methylthiopyrimidine 2- finely powdered in a reaction vessel at 0 ° C. in 750 ml of dioxane and 250 ml of water. Charge the suspension to which 50 g of chloro-4-amino-5-cyano-6-methylthiopyrimidine was added. While stirring without refrigeration, a strong salt gas stream is passed through this suspension. After about 20 minutes a clear solution forms. The chlorine introduction is stopped after 30 minutes and the batch is stirred for 0.5 hours. The reaction mixture is concentrated by evaporation and the residue is suspended in 600 ml of ice water and the suspension is filtered. 46.4 g of residual 2-chloro-4-amino-5-cyano-6-methylsulfonyl pyrimidine (decomposed at melting point of 253 ° C.) is stirred in 25 g of 30% aqueous ammonia solution and 1000 ml of acetonitrile for 2 hours at room temperature. The batch is concentrated by evaporation, the residue is suspended in water and the suspension is filtered to give the title compound of the following general formula having a melting point of 260 ° C. or higher. (Compound 5.1)

The compounds of formula (I) are also prepared according to the methods described above:

Salts of the general formula (I) are prepared by reaction with each acid.

Compounds of the general formula (I) can be prepared as described above:

Intermediates of the following general formula (II) are prepared as described above:

Intermediates of the following general formula (II) may be prepared as described above:

Intermediates of the following general formula (IX) are prepared as described above.

Intermediates of the general formula (XI) can also be prepared as described above:

Example 6:

Formulation of active ingredients according to Examples 1 to 3 or combinations of these ingredients with other pesticides or tick repellents

(Hereinafter, based on weight of percent)

1.wetting powder

The active ingredient or combination is thoroughly mixed with the adjuvant and the mixture is thoroughly milled in a suitable mill to give a wettable powder which can be a suspension of the required concentration when diluted with water.

2. Emulsifiable Concentrate

Active ingredient or combination 10%

Octylphenol polyethylene glycol ether 3%

(4-5 mol of ethylene oxide)

Calcium Dodecylbenzene Sulfonate 3%

Castor oil polyglycol ether 4%

(36 mol of ethylene oxide)

Cyclohexanone 30%

Xylene Mixture 50%

Any concentration of emulsion required may be obtained by diluting this concentrate with water.

3. Spray

The active ingredient is mixed with the carrier and the mixture is ground in a suitable mill to obtain a ready-to-use spreading agent.

4. Extruded Granule

Active ingredient or combination 10%

Sodium lignosulfonate 2%

Carboxymethylcellulose 1%

Kaolin 87%

The active ingredient or combination is mixed and ground with the adjuvant, and the mixture is then wetted with water. The mixture is extruded and then dried in air stream.

5. Cloth granulation

Active ingredient or combination 3%

Polyethylene glycol (molecular weight 200) 3%

Kaolin 94%

In a mixer, the finely divided active ingredient or combination is administered to kaolin moistened with polyethylene glycol. In this way, a dust-free coating particle is obtained.

6. Suspension concentrate

40% active ingredient or formulation

Ethylene Glycol 10%

Nonylphenol Polyethylene Glycol Ether 6%

(1 mol of ethylene oxide)

Sodium lignosulfonate 10%

Carboxymethylcellulose 1%

37% aqueous formaldehyde solution 0.2%

Silicone oil in the form of 75% emulsion solution 0.8%

32% of water

The finely divided active ingredient or combination is intimately mixed with the adjuvant and diluted with water to give a suspension concentrate which can yield the suspension of any concentration required.

7. Pour solution

Active ingredient30.00 g

Sodium dioctylsulfosuccinate 3.00 g

Benzyl Alcohol35.46g

Ethylene Glycol Monoethyl Ether

103.92g = 100ml

With vigorous stirring, the active ingredient is dissolved in most of the two solvent mixtures. Then, sodium dioctylsulfosuccinate is dissolved in the resulting solution while heating, if necessary, and the remaining dissolution mixture is added.

Example 7:

Action on housefly

50 g of freshly prepared CMSA nutrient substrate for maggots are loaded into a number of beakers. Pipette a volume of acetone solution containing 1% by weight of each test compound into the nutrient substrate present in the beaker to bring the concentration of the active ingredient to 800 ppm. This substrate is mixed thoroughly and the acetone is then evaporated over 20 hours.

25 daily housefly maggots are then placed in each beaker containing nutrient substrates treated with each active ingredient at the concentrations given for testing.

After the maggots are chrysalis, the chrysalis is shed from the substrate by shedding water and then the perforated plugs are deposited in a container.

Count each batch of washed pupa to determine the toxic effects of this test compound on maggot growth. After 10 days count the number of flies hatched from the pupa.

The general formulas (I) and (II) compounds according to Examples 1 to 3 show good activity in this test.

Example 8:

Action on Lucilia sericata

1 ml of an aqueous solution of formulation containing 0.5% of the test compound at 50 ° C. is added to 9 ml of medium. Subsequently, about 30 freshly hatched Lucilia sericata larvae are added to this medium, and the insecticidal action is measured by evaluating mortality after 48 and 96 hours.

In this test, the compounds of general formulas (I) and (II) according to Examples 1 to 3 show good activity against Lucilia cericata.

Example 9:

Action on Lucilia cuprina

Freshly deposited flies (Lucilia cuprina) eggs are added in small numbers (30-50) each into a number of test tubes with 1 ml of test solution and 4 ml of nutrient medium mixed. After inoculation of the medium, the test tube is sealed with a cotton cap and then incubated for 4 days in an incubator at 30 ° C.

In the untreated medium for control, an approximately 1 cm long (3 stage) oil layer develops by the end of this 4 day period. If the substance is active, the oil layer is fatal or almost dead by the end of this period.

Chasing oil beds is also considered because it causes the oil layers to leave the media and consequently starve.

In this test, the compounds of the general formulas (I) and (II) according to Examples 1 to 3 are very effective against Lucilia cuprina.

Example 10

Action on Aedes aegypti

An amount of a 1% solution of the test compound in acetone is pipetted and added to the surface of 150 ml water in a beaker to obtain a 800 ppm solution. After the acetone has evaporated, 30 to 40 perennial edes edge larvae are placed in a beaker containing the test compound.

Lethality is measured after 1, 2 and 5 days.

In this test, the compounds of general formulas (I) and (II) according to Examples 1 to 3 show good activity against edes easyfit.

Example 11:

Insecticidal action against eroded pests

An approximately 25 cm high cotton crop in the pot is sprayed with an emulsified solution containing individual test compounds at concentrations of 100, 200 and 400 pm. After the spray coat is dry, the cotton crops are infected with the Spodoptera litoralis and Heliotis viresense larvae at the L ₃ -stage. This test is performed at 24 ° C. and 60% relative humidity. After 2 days the larval mortality is measured.

In this test, compounds 1.1 and 1.2 exhibit 80-100% mortality relative to the Spodoptera oil layer at 200 and 400 ppm concentrations, respectively. Compounds 1.1 and 1.2 exhibit 80-100% mortality against heliotis larvae at concentrations of 100 ppm and 400 ppm, respectively.

Example 12:

Action on antonomus grandis

Two cotton crops in the 6-leaf stage in Fort are sprayed with an aqueous wettable emulsion formulation containing 400 ppm of the test compound.

After the spray coating is dry (about 1.5 hours), each crop is infected with 10 adult scarabs (Antonomos grandis). The gauze stopper prevents the movement of the scarab from the crop by pushing the treated crop infected with the test pest into a plastic cylinder. The treated crops are then stored at 25 ° C. and 60% relative humidity.

After 2, 3, 4 and 5 days, evaluation is made to determine the mortality (percent in the back) of the scarab as well as the anti-erosive action compared to the control untreated crop.

The general formulas (I) and (II) compounds according to Examples 1 to 3 show good activity in this test.

Example 13:

Action on true mites

A) African True Mite (Amblyomma hebraeum)

50 pupa are placed in a test tube and soaked in 2 ml of an emulsified solution prepared using a diluent to contain 400 ppm of the test compound for 1-2 minutes. The test tube is then sealed with a standard cotton cap and the cotton is placed at a test tube height that can absorb the emulsion. Evaluate after 1 week. Two experiments are conducted for each test compound.

B) Bophylus microplus (larvae: Boophilus microplus)

The test is carried out with 20 op-sensitive larvae and 20 op-resistant larvae using a diluent series similar to that used in Test A. (Resistant means tolerance to diazinon) Example 1 in this experiment The compounds of general formulas (I) and (II) according to the present invention are very effective against pupa and larvae of African true mite and Buphylus microfluidic mite.

Example 14

Insecticidal effect: Nilaparvata Lugens

The crop is sprayed with a solution containing 400 ppm of test compound. After the spray coating has been dried, the crop is infected with the nipalpartarugens pupa at either N ₂ or N ₃ stage. Two crops per test compound and specimen are used. The mortality rate is assessed after 6 days.

This test is performed at 26 ° C. and 60% relative humidity. In this test, the effect of 80-100% on the chrysalis of compound 1.1 nitraprata rugens.

Example 15:

Action on soil (Diabrotica balteata)

Five corn seedlings 1 to 3 cm high and filter paper discs are immersed in an aqueous solution of test compound containing 4% by volume acetone.

The impregnated filter paper discs are laid on the bottom of a 200 ml plastic beaker. On this first disc, dry filter paper discs with corn seedlings and Diabrotica Valteata larvae in the L ₂ -or L ₃ -stage are placed. The test is carried out at about 24 ° C. and 40-60% relative humidity and light.

After 6 days, it is evaluated compared to the untreated control.

In this test, Compound 1.15 shows 80-100% mortality at 400 ppm concentration.

Example 16:

Action against Nephotetti x cincticeps

The test is carried out as a growing crop. For this purpose, a rice crop of about 20 days old and about 15 cm in height is implanted into each of a plurality of pots (5.5 cm in diameter).

Crop in each pot is sprayed with 100 ml of acetone solution containing 400 ppm of this test compound on a rotating table. After the spray coating has dried, each crop is infected with 20 pupa of test organisms in the second or third stage. Place each crop in a holding glass cylinder and seal it with a gauze stopper to prevent cicadas from running away. Store the pupa for 5 days on the treated crop that must be re-sprayed at least once. This test is conducted at about 23 ° C. and 55% relative humidity. The crop is exposed to light for 16 hours a day.

In this test, compound 1.1 according to Example 1 has an effect of 80-100%.

Example 17:

Insecticidal gastric toxic effects on Flutella xylostella

The potted four-leaf Chinese cabbage crop (pot size: 10 cm diameter) is sprayed with an emulsified solution containing the test compound at a concentration of 3 to 400 ppm and dried on the crop.

After 2 days, the individually treated Chinese cabbage crops are infected with 10 fluteella xylostella larvae at the L ₂ -stage. The test is carried out at 24 ° C. and 60% relative humidity in dim light. After 2 and 5 days, larval mortality is assessed to determine mortality.

Formula (I) compounds according to Examples 1-4 show 80-100% mortality in this test.

Claims (13)

Compounds of the general formula (I) in free or salt form:

Wherein R ₁ is C ₁ -C ₆ alkyl, C ₂ -C ₆ alkenyl or C ₂ -C ₆ alkynyl and R ₂ is hydrogen, C ₁ -C ₁₀ alkyl or C ₃ -C ₆ cycloalkyl Or R ₁ and R ₂ taken together are a radical selected from the group consisting of — (CH ₂ ) ₃ —, — (CH ₂ ) ₄ — and — (CH ₂ ) ₅ —, where R ₃ is hydrogen or —CO—R ₅ Or a -SO ₂ -R ₆ radical, R ₄ is -NH ₂ , -NH-CO-R ₅ , -NH-SO ₂ -R ₆ ,

And -NH-CH = NR ₁₀ , and R ₅ is hydrogen, C ₁ -C ₁₂ alkyl, C ₃ -C ₆ cycloalkyl, C ₁ -C ₆ alkoxy, perhalogenated C ₁ -C ₃ alkyl or

Is a radical, R ₆ is C ₁ -C ₆ alkyl, R ₇ is hydrogen or C ₁ -C ₆ alkyl, and R ₈ and R ₉ are each independently hydrogen or C ₁ -C ₆ alkyl or R ₈ and R ₉ is a radical selected from the group consisting of — (CH ₂ ) ₃ —, — (CH ₂ ) ₄ — and — (CH ₂ ) ₅ —, and R ₁₀ is —SO ₂ —R ₁₃ or

And R ₁₁ and R ₁₂ are each independently hydrogen or C ₁ -C ₆ alkyl or R ₁₁ and R ₁₂ are taken together to form — (CH ₂ ) | _Is a radical selected from the group consisting of ₃ -,-(CH ₂ ) ₄ -and-(CH ₂ ) _5- , R ₁₃ is C ₁ -C ₁₀ alkyl, C ₁ -substituted by up to 10 halogen atoms C ₁₀ alkyl or C ₃ -C ₆ cycloalkyl, R ₁₄ and R ₁₅ are each independently C ₁ -C ₁₀ alkyl, and X and Y are each independently oxygen or sulfur. The compound of claim 1, wherein R ₁ is hydrogen or C ₁ -C ₄ alkyl and R ₂ is C ₁ -C ₄ alkyl or C ₃ -C ₆ cycloalkyl, or R ₁ and R ₂ are combined to form — (CH ₂ ) ₄ -or-(CH ₂ ) ₅ -radical, R ₃ is hydrogen, R ₄ is -NH ₂ or -NH-CO-R ₅ radical and R ₅ is C ₁ -C ₄ alkyl or perhalogenated C ₁ A compound of formula (I) that is -C ₃ alkyl The compound of claim 2, wherein R ₁ is hydrogen, methyl or ethyl, R ₂ is C ₁ -C ₄ alkyl or cyclopropyl, R ₃ is hydrogen, R ₄ is —NH ₂ or —NH—CO—R ₅ A compound of formula (I) wherein it is a radical and R ₅ is C ₁ -C ₃ alkyl. 4. The general formula of claim 3, wherein R ₁ is hydrogen, methyl or ethyl, R ₂ is cyclopropyl, R ₃ is hydrogen and R ₄ is -NH ₂ or -NH-CO-C ₂ H ₅ radical ( Compound of I). A compound in free form according to claim 4 having the general formula:

The compound in free form according to claim 3, having the general formula:

A compound in free form according to claim 4 having the general formula:

The compound in free form according to claim 3, having the general formula:

In order to prepare the compound of the general formula (I) in free form, the compound of the general formula (II) below is reacted with ammonia, and to prepare the compound of the general formula (I) in salt form, A process for preparing a compound of formula (I) in free or salt form, wherein R ₃ according to claim 1 is hydrogen or R ₄ is —NH ₂ , comprising converting the compound of (I) to its salt form:

Wherein R ₁ , R ₂ , R ₃ and R ₄ are as defined in claim 1 and n is 0,1 or 2. A pesticide composition comprising as an active ingredient a compound of formula (I) in free or salt form as claimed in claim 1 and at least one adjuvant. To prepare a compound of formula (I) in free form, to react a compound of formula (III) with an amine of formula (IV) and to prepare a compound of formula (I) in salt form, A compound of formula (I) wherein R _{3 in} free or salt form according to claim 1 is hydrogen and R ₄ is -NH ₂ , comprising converting the compound of formula (I) in free form to its salt form Method of preparation:

Wherein R ₁ , R ₂ , R ₃ and R ₄ are as defined in claim 1. To prepare a compound of formula (I) in free form, a compound of formula (I) wherein R ₃ is hydrogen and R ₄ is -NH ₂ is known in a known manner in which R ₃ is hydrogen and R ₄ is -NH. _To convert to a compound of formula (I) other than ₂ and to prepare a compound of formula (I) in salt form wherein R ₃ is hydrogen and R ₄ is not -NH ₂ , R ₃ is hydrogen and R A free or salt form wherein R ₃ according to claim 1 is hydrogen and R ₄ is not -NH ₂ , which comprises converting the compound of formula (I) in free form other than _tetravalent -NH ₂ to its salt form. Method for producing a compound of formula (I). In order to prepare a compound represented by the general formula (I) in free form, R ₃ is hydrogen in the compound of formula (I) by known manner R ₃ a was converted to compound of formula (I) other than hydrogen In R ₃ In order to prepare a compound of the compound of formula (I) in salt form other than hydrogen, R ₃ is claimed in claim 1 which comprises converting the compound of formula (I) in free form other than hydrogen to its salt. A process for preparing a compound of formula (I) in free or salt form, wherein one R ₃ is not hydrogen.