MXPA00001698A - Method for producing substituted-2-nitroguanidine derivatives - Google Patents

Abstract

The invention relates to a method for producing an organic compound of formula (I) and optionally its E/Z-isomers, E/Z-isomer mixtures and/or tautomers, each in free or salt form, R1 representing hydrogen or C1-C4 alkyl, R2 representing hydrogen, C1-C6 alkyl, C3-C6 cycloalkyl or a radical -CH2B, Het representing an unsubstituted or substituted heterocyclic radical and B representing phenyl, 3-pyridyl or thiazolyl, these being optionally substituted. The invention is characterised in that a compound of formula (IIa) Q-A-Q, wherein A represents a direct bond or an organic radical, or of formula (IIb), wherein U represents an organic radical, Q representing (1) in the compounds (IIa) and (IIb) and R1, R2 and Het having the meaning given above for formula (I), and optionally their E/Z-isomers, E/Z-isomer mixtures and/or tautomers, each in free or salt form are hydrolysed. The invention also relates to a method for producing compounds of formulae (IIa), (IIb), (IIIa) and (IIIb), and to a method for combating pests with compounds of formulae (IIa) and (IIb).

Description

METHOD FOR PRODUCING SUBSTITUTE 2-NITROGUANIDINE DERIVATIVES The present invention relates to a novel type of method for producing substituted 2-nitroguanidine derivatives.

It is known that, in order to produce 1, 3-disubstituted 2-nitroguanidines, an additional substituent can be introduced into the monosubstituted 2-nitroguanidines (eg, by alkylation) (see, for example, European Patent Applications). Numbers 0.375.907, 0.376.279, and 0.383.091). Due to the presence of three reactive hydrogen atoms in the monosubstituted 2-nitroguanidines used as the starting material in these reactions, the previously proposed substitution reactions of this kind are often not selective, and lead to undesired substitution products. The aforementioned European patent applications describe the production of 1,3-disubstituted 2-nitroguanidines by the reaction of monosubstituted nitroisothioureas with primary amines while the mercaptan is dissociated. However, these nitroisothiourea compounds, which contain thioalkyl leaving groups, which are proposed as starting compounds in the known processes, can only be obtained with difficulty. In addition, in the European Patent Number EP-A-0-483, 062, a method for producing the compounds of the formula (I) by hydrolysis of hexahydro-triazines is described.

It has now been shown that the above-described methods for producing compounds of the formula (I) do not meet the demanded requirements of a chemical production process, such as availability, toxicity, storage stability, and purity of the starting materials and materials. excipients, reaction time, energy consumption, and volumes produced through the process, quantity and recovery of by-products and accumulated waste products, as well as purity and yield of the final product. Accordingly, there is a need to provide improved methods for producing these compounds. It has now been found in a surprising manner that the method according to the invention can satisfy these requirements to a great degree.

In accordance with the foregoing, it is the object of the present invention to provide an improved method for producing 1-monosubstituted and 1,3-disubstituted 2-nitroguanidines from readily available starting compounds, which allows for the -specific substitution without obtaining larger quantities of unwanted byproducts.

The objective of the invention is: a) A method for producing a compound of the formula: and, if appropriate, the E / Z isomers, E / Z isomeric mixtures, and / or tautomers thereof, each in free form or in salt form, wherein: Rj_ is hydrogen or alkyl of 1 to 4 atoms of carbon; R- is hydrogen, alkyl of 1 to 3 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or a radical -CH 2 B; Het is a heterocyclic aromatic or non-aromatic, monocyclic or bicyclic radical, which is unsubstituted, or - depending on the possibilities of substitution of the mono- to penta-substituted ring system with substituents selected from the group comprising halogen, alkyl from 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms, haloalkoxy of 1 to 3 carbon atoms, cyclopropyl, halocyclopropyl, alkenyl of 2 to 3 carbon atoms, alkynyl of 2 to 3 carbon atoms, haloalkenyl of 2 to 3 carbon atoms, and haloalkynyl of 2 to 3 carbon atoms, thioalkyl of 1 to 3 carbon atoms, halotioalkyl of 1 to 3 carbon atoms, allyloxy, propargyloxy, thioalyl, thiopropargyl, haloalyloxy, halothioalyl, cyano, and nitro; and B is phenyl, 3-pyridyl, or thiazolyl, which are optionally substituted by one to three substituents from the group comprising alkyl of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms, cyclopropyl, halocyclopropyl , alkenyl of 2 to 3 carbon atoms, alkynyl of 2 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, haloalkenyl of 2 to 3 carbon atoms, haloalkynyl of 2 to 3 carbon atoms, haloalkoxy of 1 to 3 carbon atoms, thioalkyl of 1 to 3 carbon atoms, halotioalkyl of 1 to 3 carbon atoms, allyloxy, propargyloxy, thioalyl, thiopropargyl, haloalyloxy, halothioalyl, halogen, cyano, and nitro; characterized by hydrolyzing a compound of the formula: Q-A-Q (Ha), where A is a direct bond or an organic radical; or of the formula: Q 1 (Ilb), Q Q where U is an organic radical; and in the compounds (Ha) and (Ilb), Q means and R1 (R2, and Het are as defined above for formula (I), and optionally the E / Z isomers, E / Z isomeric mixtures, and / or tautomers thereof, each in free or in the form of salt The compounds of the formula (I) can be present as E / Z isomers, for example in the following two isomeric forms: Y According to the foregoing, it is understood that any reference to the compounds of the formula (I) hereinabove and subsequently herein also includes their corresponding E / Z isomers, even when the latter are not specifically mentioned in each case .

The compounds of the formula (I) may be partially present in the form of tautomers. In accordance with the foregoing, it is understood that any reference to the compounds of the formula (I) hereinabove and subsequently herein also includes their corresponding tautomers, even when the latter are not specifically mentioned in each case. The compounds of the formula (I), and where appropriate, the E / Z isomers and tautomers thereof, may be present as salts. The compounds of the formula (I) having at least one basic center can form, for example, acid addition salts. These are formed, for example, with strong inorganic acids, such as mineral acids, for example sulfuric acid, a phosphoric acid, or a hydrohalic acid, or with strong organic carboxylic acids, such as substitutedcarboxylic acids of 1 to 4 carbon atoms. where appropriate, for example by halogen, for example acetic acid, such as optionally unsaturated dicarboxylic acids, for example oxalic, malonic, maleic, fumaric, or phthalic acid, such as hydroxycarboxylic acids, for example ascorbic, lactic, malic, tartaric acid , or citric, or benzoic acid, or with organic sulfonic acids, usually C 1 to C 4 alkylsulfonic acids or substituted arylsulfonic acids where appropriate, for example by halogen, for example methan-, trifluoromethane-, or p-toluene- sulphonic The salts of the compounds of the formula (I) with acids of that class are preferably obtained when the reaction mixtures are processed. In a broader sense, the compounds of the formula (I) with at least one acid group can form salts with bases. Salts with suitable bases are, for example, metal salts, usually alkali metal or alkaline earth metal salts, for example sodium, potassium, or magnesium salts, or salts with ammonia or an organic amine, such as morpholine, piperidine, pyrrolidine, a mono-, di-, or tri-lower alkylamine, for example ethyl-, diethyl-, triethyl-, or dimethyl-propylamine, or a mono-, di-, or tri-hydroxyalkylamine, for example mono-, di-, , or tri-ethanolamine. The corresponding internal salts can also be formed when appropriate. Preferred compounds within the scope of this invention are agrochemically convenient salts. Formerly herein and hereinbelow, it is understood that the free compounds of the formula (I), where appropriate, also include, by analogy, the corresponding salts, or it is understood that the salts also include the free compounds of the formula (I). The same applies to the E / Z isomers and tautomers of the compounds of the formula (I), and salts thereof. The free form is preferred. The statements made about the free compounds of the formula (I) or the E / Z isomers and tautomers and salts thereof, are also applied, by analogy, to the compounds of the formulas (Ha) and (Hb), as well as to the compounds of the formulas (Illa) and (Illb) that are found later. In the definitions of the previous formulas (I), (Ha), (Hb), and of the compounds of the formulas (Illa) and (IHb) that are found below, the individual generic terms should be understood as follows: The halogen atoms considered as substituents can be both fluorine as chlorine, and bromine and iodine, where fluorine, chlorine, and bromine, especially chlorine, are preferred. It is understood that halogen in this context is an independent substituent or part of a substituent, such as in haloalkyl, halothioalkyl, haloalkoxy, halocycloalkyl, haloalkenyl, haloalkynyl, haloalyloxy, or halothioalyl. The alkyl, thioalkyl, alkenyl, alkynyl, and alkoxy radicals considered as substituents can be straight or branched chain. Examples of these alkyls that may be mentioned are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secondary butyl, or tertiary butyl. Suitable alkoxy radicals which may be mentioned are, inter alia: methoxy, ethoxy, propoxy, isopropoxy, or butoxy, and the isomers thereof. Thioalkyl is, for example, thiomethyl, thioethyl, thioisopropyl, thiopropyl, or isomeric thiobutyl.

If the alkyl, alkoxyl, alkenyl, alkynyl, or cycloalkyl groups, considered as substituents, are substituted by halogen, they may be only partially halogenated, or else perhalogenated. The above-mentioned definitions apply here to halogen, alkyl, and alkoxy. Examples of the alkyl elements of these groups are methyl which is mono- to tri-substituted by fluorine, chlorine, and / or bromine, such as CHF2 or CF3; ethyl which is mono- to penta-substituted by fluorine, chlorine, and / or bromine, such as CH2CF3, CF2CF3, CF2CC13, CF2CHC12, CF2CHF2, CF2CFC12, CF2CHBr2, CF2CHC1F, CF2CHBrF, or CClFCHClF; propyl or isopropyl, mono- to hepta-substituted by fluorine, chlorine, and / or bromine, such as CH2CHBrCH2Br, CF2CHFCF3, CH2CF2CF3 or CH (CF3) 2; butyl or one of its isomers, mono- to nona-substituted by fluorine, chlorine, and / or bromine, such as CF (CF3) CHFCF3Odi, (CF2) 2CF3; 2-chlorocyclopropyl, or 2,2-difluorocyclopropyl; 2, 2-difluorovinyl, 2,2-dichlorovinyl, 2-chloroalkyl, 2,3-dichlorovinyl, or 2,3-dibromovinyl. If the defined alkyl, alkoxyl, or cycloalkyl groups are substituted by other substituents, they may be substituted once or repeatedly by substituents identical or different from the ones listed. In the substituted groups, it is preferable that one or two additional substituents are present. The cycloalkyl radicals considered as substituents can be, for example, cyclopropyl, cyclobutyl, cyclopentyl, or cyclohexyl. The alkenyl and alkynyl groups contain an unsaturated carbon-carbon bond. Typical representatives are allyl, methallyl, or propargyl, but also vinyl and ethynyl. The double or triple bonds in allyloxyl, propargiloxyl, thioalyl, or thiopropargyl, are separated from the point of connection with the heteroatom (O or S) preferably by a saturated carbon atom. As with the aforementioned alkyl, alkenyl, and alkynyl groups, the alkylene, alkenylene, and alkynylene groups defined in the following may also be straight or branched chain. Examples are -CH2-CH2-, -CH2-CH2-CH2-, - -CH2-CH2-CH2-CH2-, CH2-C (CH3) H-, and -C (CH3) H-C (CH3) H-. The alkylene, alkenylene, alkynylene, cyclalkylene, arylene, or heterocyclyl groups mentioned below, where appropriate, are substituted in the same manner as the aforementioned alkyl, alkenyl, and alkynyl groups. Aryl or arylene means phenyl or naphthyl, or phenylene or naphthylene, especially phenyl or phenylene. In the context of the present invention, the heteroaryl radical indicated as Het preferably means an aromatic or non-aromatic ring of 5-7 members, with one to three heteroatoms selected from the group comprising N, O, and S. it gives preference to the 5 and 6 membered aromatic rings, which have a nitrogen atom as the heteroatom, and optionally an additional heteroatom, preferably nitrogen, oxygen, or sulfur, especially nitrogen. It has now been discovered in a surprising manner that the method according to the invention can satisfy the requirements mentioned initially. The hydrolysis process according to the invention can be carried out in both an acidic and a basic medium.

In the acid range, pH values of 6 or less, especially 1 to 3, are preferred. In the basic range, a pH value greater than 7 and up to 12, especially from 8 to 12, in particular 8, is preferred. to 10. The reaction is carried out at a normal pressure and at a temperature of 0 ° C to 120 ° C, preferably 20 ° C to 80 ° C. The reaction is carried out in a solvent or diluent which is inert towards the components of The reaction Suitable solvents are, in particular, alcohols, such as methanol, ethanol, propanol, and isopropanol, as well as especially water.

Other suitable solvents are, for example, ethers, such as tetrahydrofuran and dioxane, as well as other solvents that do not adversely affect the reaction. Solvents can also be used as mixtures. A compound of the formula (II) is preferably hydrolyzed in an aqueous medium, or in a mixture of water with an alcohol. Suitable acids to carry out the process of preference are mineral acids, for example sulfuric acid, a phosphoric acid, or a hydrohalic acid, an organic carboxylic acid, usually substituted alkanocarboxylic acids of 1 to 4 carbon atoms where appropriate, for example by halogen, for example acetic acid, such as dicarboxylic acids which are unsaturated when necessary, for example oxalic, malonic, maleic, fumaric, or phthalic acid, usually hydroxycarboxylic acids, for example ascorbic, lactic, malic, tartaric, or citric acid, or benzoic acid, or an organic sulfonic acid, usually C 1 to C 4 alkylsulfonic acids or substituted arylsulfonic acids where appropriate, for example by halogen, for example methanesulfonic or p-toluenesulfonic acid. Suitable bases for carrying out the process are preferably hydroxides of alkali metals and alkaline earth metals, such as NaOH and KOH, carbonates, such as Na 2 CO 3, NaHCOa, KjCOj; phosphates, such as Na3P04, Na2HPOe, a.cocolates such as sodium methanolate, sodium ethanolate, and tertiary potassium butanolate, organic amines such as morpholine, piperidine, pyrrolidine, a mono-, di-, or tri- idroxyalkylamine lower, for example mono-, di-, or tri-ethanolamine, or dialkylaniline, for example N, N-dimethyl- or N, N-diethyl-aniline, as well as salts of organic acids, such as sodium acetate, potassium acetate, or sodium benzoate, or mixtures thereof, for example acetate or phosphate regulators. Particularly convenient reaction conditions are described in the examples. The method according to the invention is preferably used to produce compounds of the formula (I), wherein the heterocyclic radical Het is unsaturated and is linked by a carbon atom as a ring member, with the substantive substance. Especially preferred Het radicals are pyridyl, thiazolyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, N-oxide-pyridinium, oxazolyl, isoxazolyl, thienyl, morpholinyl, piperidinyl, pyridinyl, and pyrazinyl; in a particular manner pyridyl, thiazolyl, tetrahydrofuranyl, and N-oxide-pyridinium; more particularly 3-pyridyl, 2-halopyrid-5-yl, 2,3-dihalopyrid-5-yl, 2-halothiazol-5-yl, tetrahydrofuran-3-yl, 2-methyl-tetrahydrofuran-4-yl, l- oxopyrid-3-yl, l-oxo-2-halopyrid-5-yl, and l-oxo-2,3-dihalopyrid-5-yl. Likewise, Het heterocycles carry one to three substituents from the group of halogen, alkyl of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms, and haloalkoxy of 1 to 3 carbon atoms, each one with 1 to 7 halogen atoms, and alkoxy of 1 to 3 carbon atoms, more preferably chlorine or methyl. In addition, the compounds of the formula (I) are preferably produced according to the invention, wherein the radical B is a phenyl, pyridyl, or thiazolyl radical which is unsubstituted, or which may be substituted by one to two radicals. from the group of halogen, alkyl of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms, and haloalkoxy of 1 to 3 carbon atoms, each with 1 to 7 halogen atoms, and alkoxy of 1 to 3 carbon atoms. Of the compounds of the formula (I) which are to be produced according to the invention, the notorious ones are those in which: R is hydrogen; R2 is hydrogen, alkyl of 1 to 3 carbon atoms, or cyclopropyl; especially hydrogen, methyl, ethyl, or cyclopropyl, in particular methyl; and Het is pyridyl, 1-oxopyridyl, tetrahydrofuranyl, thiazolyl; or pyridyl, 1-oxide-pyridinium, tetrahydrofuranyl, or thiazolyl, respectively substituted by one to three substituents from the group of halogen, alkenyl of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms, as well as haloalkoxy 1 to 3 carbon atoms with 1 to 7 halogen atoms, and alkoxy of 1 to 3 carbon atoms; especially 2-chloropyrid-5-yl, tetrahydrofuran-3-yl, 2-methyl-tetrahydrofuran-4-yl, or 2-chlorothiazol-5-yl. In order to carry out the process according to the invention, on the one hand, those compounds of the formula (lía) are preferably used, wherein A is alkylene of 2 to 20 carbon atoms, alkenylene of 2 to 20 carbon atoms, alkynylene of 2 to 2O carbon atoms, cycloalkylene of 3 to 12 carbon atoms, arylene, or heterocyclylene, straight or branched chain; wherein the alkylene groups of 2 to 20 carbon atoms, alkenylene of 2 to 20 carbon atoms, alkynylene of 2 to 20 carbon atoms, cycloalkylene of 3 to 12 carbon atoms, arylene, and heterocyclylene, are optionally substituted 0 several times, independently of one another, and the alkylene groups of 2 to 20 carbon atoms, alkenylene of 2 to 20 carbon atoms, and alkynylene of 2 to 20 carbon atoms are optionally interrupted once or several times, independently O, NH, or N-alkyl of 1 to 12 carbon atoms, cycloalkylene of 3 to 9 carbon atoms, arylene, or heterocyclylene; or a group -D: L-O2-O3 -; wherein DL and D3, independently of each other, mean cycloalkylene of 3 to 12 carbon atoms or optionally substituted arylene, and D2 means alkylene of 2 to 20 carbon atoms, alkenylene of 2 to 20 carbon atoms, alkynylene of 2 to 20 carbon atoms, O, NH, or N-alkyl of 1 to 12 carbon atoms. Particularly preferred bridge members A are alkylene of 2 to 12 carbon atoms, alkylene of 2 to 12 carbon atoms interrupted by one or two phenylene, cyclohexylene, or piperazinylene radicals; cyclohexylene or phenylene; or the group -O 1 -O 2 -O 3 -, wherein O 1 and D 3 are phenylene or dicyclohexylene, and D 2 is O or alkylene of 2 to 4 carbon atoms; A especially means alkylene of 2 to 4 carbon atoms. On the other hand, in order to carry out the process according to the invention, preferably the compounds of the formula (IIb) are used as the starting material, wherein U is aryl, heterocyclyl, cycloalkyl of 3 to 12. carbon atoms, or a group: wherein:., Aa, and A3, independently of each other, have the same meanings as given above for A in the formula (lia), and X means N or CH.

A and U as heterocyclyl in the compounds of the formulas (Ha) and (Hb) are preferably an aromatic or non-aromatic ring, of three to ten members. If the rings A and U are non-aromatic heterocyclic rings, they are especially piperidinyl, piperazinyl, morpholinyl, pyrrolidinyl, tetrahydrofuranyl, and dioxolanyl. The radicals A ^, A ^, and A3, independently of one another, are more preferably alkylene of 2 to 4 carbon atoms, especially ethylene.

A further object of the invention is: b) A method for producing a compound of the formula (Ha) and (Hb), wherein a compound of the formula is reacted: T-A-T (Illa), or of the formula: x (nib), where A and U have the same meaning as defined above for formulas (Ha) and (Hb); and R2 has the same meaning as defined above for formula (I); and optionally the E / Z isomers, isomeric mixtures E / Z, and / or tautomers thereof, each in free form or in salt form, when a compound of the formula is produced (Illa) with two equivalents, or when a compound of the formula (IHb) is produced with three equivalents of a compound of the formula: Y. .Het R. (IV) which is known or can be produced in a manner analogous to the methods known per se, wherein R. and Het are defined as given above for formula (I), and Y is a leaving group, preferably in the presence of a base. The following can be considered as the groups "Y" in the context of the described operating method: halogen, preferably chlorine, bromine, or iodine, especially chlorine, or sulphonic acid radicals, such as acid radicals, alkylsulfonic acid mesylate or tosylate. The process step according to b) can be carried out preferably at a normal or slightly elevated pressure, and in the presence of preference of aprotic solvents or diluents. Suitable solvents or diluents are, for example, ethers and ether-type compounds, such as diethyl ether, dipropyl ether, dibutyl ether, dioxane, dimethoxyethane, and tetrahydrofuran; aliphatic, aromatic, and halogenated hydrocarbons, especially benzene, toluene, xylene, chloroform, methylene chloride, carbon tetrachloride, and chlorobenzene; nitriles, such as acetonitrile or propionitrile; dimethyl sulfoxide or dimethyl formamide, as well as mixtures of these solvents. This step of the process is generally carried out at a temperature of -20 ° C to + 140 ° C, preferably between 0 ° C and + 120 ° C, preferably in the presence of a base. Suitable bases are, for example, carbonates, such as sodium and potassium carbonate. Hydrides can also be used as bases, for example sodium hydride, potassium hydride, and calcium hydride. If required, the reaction can also be carried out in the presence of a catalyst, for example cesium chloride.

A further objective of the invention is c) A method for producing the compounds of the formulas (Illa) and (Hlb), wherein a compound of the formula is reacted: NH, Eyr- -NEL, (Va), or, 1I, '2 (Vb) , H2N NH, and optionally the E / Z isomers, E / Z isomeric mixtures, and / or tautomers thereof, each in free form or in salt form, wherein A and U have the same meaning as defined above for the compounds of the formulas (Ha) and (IIb), and which are known or can be produced in a manner analogous to the methods known per se, when a compound of the formula (Illa) is produced with two equivalents, or when a compound of the formula (IHb) with three equivalents of a compound of the formula: which is known or can be produced in a manner analogous to the methods known per se, and where R ^, has the same meaning as defined for formula (I), in the presence of an excess of formaldehyde or paraformaldehyde .

The process according to c) for "the preparation of the compounds of the formula (III) conveniently is carried out at a normal pressure, but also optionally at an elevated pressure in the presence of an inert solvent, and at temperatures between 0 ° C. and + 140 ° C, preferably between + 20 ° C and + 120 ° C. Suitable solvents are, in particular, alcohols such as methanol, ethanol, and propanol, as well as water.Other suitable solvents are, for example, hydrocarbons aromatics, such as benzene, toluene, and xylene, ethers, such as tetrahydrofuran, dioxane, and diethyl ether, halogenated hydrocarbons, such as methylene chloride, chloroform, carbon tetrachloride, and chlorobenzene, as well as other solvents that do not impair the reaction. The solvents can also be used as mixtures, the process optionally carried out by adding an acid catalyst, such as HCl, H2SO4, or a sulphonic acid, such as p-toluenesulfonic acid, if desired, it can be removed. er the water of the reaction, using a water separator, or by the addition of a molecular sieve.

A further objective of the invention is: d) A method for producing a compound of the formula (I), wherein a compound of the formula (Va) or (Vb) is converted to a compound of the formula (Illa) or (Hlb), by its reaction with a composed of the formula (VI) and formaldehyde or paraformaldehyde; this compound of the formula (Illa) or (IHb) is converted by a compound of the formula (IV) in a compound of the formula (Ha) or (Ilb), and this compound of the formula (Ha) or (Hb) is hydrolyzed.

Additional objects of the invention are the compounds of the formulas (Ha), (Hb), (Illa), and (IHb), and optionally the E / Z isomers, E / Z isomeric mixtures, and / or tautomers thereof , each in free form or in salt form, as well as its use in the preparation of the compounds of the formula (I). Especially preferred embodiments of the method according to variants b) to d) can be taken from the examples.

The compounds of the formula (I) produced according to the invention are known. They are valuable active ingredients in the control of pests, which are well tolerated by warm-blooded animals, fish, and plants. The compounds of the formula (I) are especially suitable for the control of insects and arachnids, which appear in crops and ornamentals in agriculture, especially in cotton, vegetable and fruit plantations, in forests, in the protection of supplies and materials, as well as in the hygiene sector, especially in domestic animals and livestock producers. The compounds are especially effective against sucking insects that damage plants, especially against aphids and grasshoppers of plants and leaves.

Example Pl.l; Preparation of the compound of the formula; A mixture of 3.0 grams of 1-methyl-2-nitroguanidine, 0.85 grams of 1,2-diaminoethane, 15 milliliters of dioxane, and 5.7 milliliters of a 37 percent solution of formaldehyde in water at room temperature is heated to 50 ° C, and stirred at this temperature for 4 hours. The mixture is then evaporated to dryness in vacuo, the residue is stirred with diethyl ether, and the title compound is isolated by filtration. P.f. 222-223 ° C (compound 1.1).

Example P1.2; Preparation of the formula of the formula: A mixture of 1.8 grams of 1-methyl-2-nitroguanidine, 1.35 grams of paraformaldehyde, and 0.78 grams of 1,5-diamino-3-oxa-pentane in 20 milliliters of toluene and 20 milliliters of dioxane is mixed at room temperature with two drops of a 37 percent solution of HCl in water, then it is heated to reflux temperature, and stirred at this temperature for 6 hours. The mixture is then evaporated to dryness in vacuo, the residue is stirred with diethyl ether, and the title compound is isolated by filtration (compound 1.15).

Example P1.3; Preparation of the compound of the formula: A mixture of 8.0 grams of l-methyl-2-nitroguanidine and 3.0 grams of 1,4-diaminobutane in 25 milliliters of ethanol is mixed at room temperature with 25 milliliters of a 37 percent solution of formaldehyde in water, heated at 50 ° C, and stirred at this temperature for 16 hours. The mixture is then evaporated to dryness in vacuo, and the residue is stirred with ethanol. The title compound is obtained with a melting point of 232-234 ° C (compound 1.4).

Example P1.4: A mixture of 6.0 grams of l-methyl-2-nitroguanidine and 5.4 grams of 4,9-dioxa-l, 12-diaminododecane in 25 milliliters of ethanol is mixed at room temperature with 19 milliliters of a 37 percent solution of formaldehyde in water, heat to 50 ° C, and stir at this temperature for 16 hours. Then the mixture is cooled to 5 ° C, filtered, and the residue is washed with a little ethanol. The title compound is obtained with a melting point of 140-143 ° C (compound 1.14).

Example P1.5: The following compounds listed in Table 1 can also be obtained analogously to the above methods of examples Pl. 1 to Pl .4.

Table 1; Compounds of the formula: No. Physical Data 1. 1 - (CHa), - p.f. 222-223 ° C 1.2-CH (CH3) 1.3 - (CH, - 1.4 _ - (CH ^ - pf 232-234 ° C 1.5 - (CH2) 5- 1.6 - (CHa) ,, - 1.7 - (CH2) 7- 1.8 - (CH2) 8- 1.9 _ - (CH2) 9- Physical Data (CH2) 10- (CH2) 12- UJ_ - U (__x / - rl2 - CH2-CH (0H) -CIL, - (CHa) 3-0- (CH2) 4-0- (CH2) mp 140-143 ° C ™ 12"~ Ox.2" ~ "" "- OHj - CH2-CH (CH3) - (CH2) 3- (CHJ 2-0- (CHa) 2-0- (CHa) (CHa) 3 -O- (CH2) 2-0- (CHa) -O- (CH2) 3- (CH2) 3-N (CH3) - (CHa) 3- / \ - (CH,), N, fN- (CH2 2) /: 3 \ / No. Physical Data Example P2.1: Preparation of the compound of the formula: A mixture of 2.4 grams of 1-methyl-2-nitroguanidine and 1.0 grams of tris (2-aminoethyl) amine in 50 25 milliliters of ethanol is mixed at room temperature with 30 milliliters of a 37 percent solution of formaldehyde in water , it is heated to 50 ° C, and stirred at this temperature for 16 hours. The mixture is then evaporated to dryness in vacuo, the residue is stirred with diethyl ether / ethyl acetate (1: 1), and the title compound is isolated by filtration (compound 2.1).

Example P2.2: The following compounds listed in Table 2 can also be obtained in a manner analogous to the previous method of Example P2.1.

Table 2: Compounds of the formula: 2. 1. - (CH2) 2- - (CHa) a- (CH, N Example P3.1: Preparation of the compound of the formula: A mixture of 2.0 grams of the product obtainable according to the example Pl.l, 1.6 grams of 2-chloro-5-chloromethylpyridine, and 2.8 grams of potassium carbonate in 20 milliliters of dimethyl formamide, is stirred for 9 hours at 90 ° C. Then, the reaction mixture is filtered, the filtrate is concentrated by evaporation in vacuo, and the residue is recovered in 100 milliliters of dichloromethane. The organic phase is washed with 50 milliliters of water and 50 milliliters of a saturated sodium chloride solution, dried over MgSO 4, and evaporated to dryness. The residue is stirred with diethyl ether, and the title compound is isolated by filtration (compound 10.B.1).

Example P3.2: Preparation of the compound of the formula: A mixture of 3.7 grams of the compound obtainable according to Example P1.3, 3.2 grams of 2-chloro-5-chloromethylpyridine, and 5.5 grams of potassium carbonate in 20 milliliters of dimethyl formamide, is stirred for 16 hours at 55 ° C. Then, the reaction mixture is filtered, the filtrate is concentrated by evaporation in vacuo, the residue is stirred in methanol, and filtration is carried out. This produces the title compound with a melting point of 178-180 ° C (compound 10.B.4).

Example P3.3: A mixture of 4.9 grams of the compound obtainable according to Example P1.4, 3.24 grams of 2-chloro-5-chloromethylpyridine, and 5.5 grams of potassium carbonate in 20 milliliters of dimethyl formamide, is stirred for 16 hours at 55 ° C. Then, the reaction mixture is filtered, the filtrate is concentrated by evaporation in vacuo, and the residue is purified on silica gel with ethyl acetate / methanol (2: 1) as eluent. This produces the title compound with a melting point of 70-72 ° C (compound 10.B.14).

Example P3.4: Compound of the formula: A mixture of 2.0 grams of the compound obtainable according to the example Pl.l, 1.95 grams of 2-chloro-5-chloromethylthiazole, and 4.0 grams of potassium carbonate, and 1.53 grams of 18-Crown-6 (1 , 5, 777, 10, 13, 16-hexaoxacyclo-octadecane) in 20 milliliters of tetrahydrofuran, is stirred for 24 hours at 50 ° C. Then, the reaction mixture is filtered, the filtrate is concentrated by evaporation in vacuo, and the residue is purified on silica gel with dichloromethane / methanol (9: 1) as eluent. This produces the title compound with a melting point of 175-178 ° C (compound 3.B.1).

Example P3.5: The following compounds listed in Tables 3 to 26 can also be obtained in a manner analogous to the above methods of Examples P3.1 to P3.4.

Table B Compounds of the formula: Not Bl - (CHa) a- B.2 -CH (CH3) -CH2- B.3 - (CH2) 3- B.4"(CH2) 4- B.5 - (CHa) s- B.6 - ( CHa) ß- B.7 - (CH2) 7- B.8 - (CH2) 8- B.9 - (CH2) 9- B.10 - (CH2) 1Q- B.ll - (CH2) 12- B .12 - CH ^ - C OH3 / 2 - CH2 - B.13 - CH2 - CH (OH) - CH2 - B.14 - (CHa) 3-0- (CHa) 4-0- (CH2) 3- B .15 - Ci2 - CH2 - O - CH2 - CH_2 - B.16 - CH2 - CH (CH3) - (CH2) 3- B.17 - (CH2) 2-0- (CH2) 2-0- (CHj) 2- B.18 - (CHa) to "0" (CH2) "0" (H2) 2- O- (CH2) 3- B.19 - (CH2) 3-N (CH3) - (CHa) 3- Not B.23 / \ - (CH2) 3- N, N- (CH2) 3- V_ / B.28 B.30 Table 3: Compounds of the general formula (He), where Het it means and A corresponds in each case to a line of Table B. Compound 3.B.01: p.f. 175-178 ° C.

Table 4: Compounds of the general formula (He), where Het it means and A corresponds in each case to a line of Table B.

Table 5: Compounds of the general formula (He), where Het it means and A corresponds in each case to a line of Table B.

Table 6: Compounds of the general formula (He), where Het it means and A corresponds in each case to a line of Table B.

Table 7: Compounds of the general formula (He), wherein Het means 2-methyl-tetrafuran-4-yl, and A corresponds in each case to a line of Table B.

Table 8: Compounds of the general formula (He), where Het means tetrafuran-3-yl, and A corresponds in each case to a line of Table B.

Table 9: Compounds of the general formula (He), where Het it means and A corresponds in each case to a line of Table B.

Table 10: Compounds of the general formula (He), where Het it means and A corresponds in each case to a line of Table B. Compound 10.B.04; p.f. 178-180 ° C. Compound 10.B.14; p.f. 70-72 ° C.

Table 11: Compounds of the general formula (He), wherein Het means pyrid-3-yl, and A corresponds in each case to a line of Table B.

Table 12: Compounds of the general formula (He), where Het __. it means and A corresponds in each case to a line of Table B.

Table 13: Compounds of the general formula (He), where Het it means and A corresponds in each case to a line of Table B.

Table 14: Compounds of the general formula (He), wherein Het means 2,3-dichloropyrid-5-yl, and A corresponds in each case to a line of Table B.

Table C: Compounds of the formula: Cl - (CHa) a- - (CHa) a- - (CHa) a- N C.2 - (CHa) 3 -CH2- - (CH2) 4 CH Table 15: Compounds of the general formula (Hd), in where Het it means and AJL, ^, 3, and X correspond in each case to a line of Table C.

Table 16: Compounds of the general formula (Hd), where Het it means and A1, Aa, A3, and X correspond in each case to a line of Table C.

Table 17: Compounds of the general formula (Hd), where Het it means and Ax, A2, A3, and X correspond in each case to a line of Table C.

Table 18: Compounds of the general formula (Hd), where Het it means and A-L, A2, A3, and X correspond in each case to a line of Table C.

Table 19: Compounds of the general formula (lid), wherein Het means 2-methyl-tetrahydrofuran-4-yl, and A? r A, A3, and X correspond in each case to a line of Table C.

Table 20: Compounds of the general formula (Hd), where Het means 3-tetrahydrofuranyl, and A ±, A ^, A3, and X correspond in each case to a line of Table C.

Table 21: Compounds of the general formula (lid), where Het it means and A ^ Aa, A3, and X correspond in each case to a line of Table C.

Table 22: Compounds of the general formula (Hd), wherein Het means 2-chloro-pyrid-5-yl, and A ^ A ^ A3, and X correspond in each case to a line of Table C.

Table 23: Compounds of the general formula (Hd), where Het means 3-pyridyl, and j, A ^, A3, and X correspond in each case to a line of Table C.

Table 24: Compounds of the general formula (Hd), where Het means and Aa, A3, and X correspond in each case to a line of Table C.

Table 25: Compounds of the general formula (Hd), where Het it means and a, A3, and X correspond in each case to a line of Table C.

Table 26: Compounds of the general formula (Hd), wherein Het means 2,3-dichloropyrid-5-yl, and Ax, ^, A3, and X correspond in each case to a line of Table C.

Example 4.1: Preparation of the compound of the formula: 1. 2 grams of the compound obtainable according to example P3.1, are stirred for 16 hours at room temperature, together with 10 milliliters of methanol and 10 milliliters of 1 N hydrochloric acid. The reaction mixture is concentrated to dryness by evaporation, and the residue is purified on silica gel with dichloromethane / methanol (95: 5) as the eluent.This produces the title product with a melting point of 147-149 ° C (compound 27.6).

Example 4.2: Preparation of the compound of the formula: 1. 2 grams of the compound obtainable according to Example P3.4, are stirred for 40 hours at 50 ° C, together with 3.3 milliliters of methanol and 3.3 milliliters of 1 N hydrochloric acid. The reaction mixture is evaporated to dryness , and the residue is recrystallized from methanol. This produces the title product with a melting point of 170-172 ° C (compound 27.1).

Example P4.3: The following compounds listed in Table 27 can also be obtained in a manner analogous to the previous methods of Examples 4.1 and 4.2.

Table 27: Compounds of the general formula: H, C N-H (i: N OzN H Het Het Physical Data pyridyl 2-chloropyrid-5-p.f. 147-149 ° C ilo 2,3-dichloropyrid-p.f. 173-174 'C 5-il? A further object of the invention is a method for controlling pests, especially pests of animals, particularly insects and members of the order Acariña, using the compounds of the formulas (Ha) and (Hb). These animal pests include, for example, those mentioned in European Patent Application Number EP-A-736,252. Accordingly, the pests mentioned therein are included as reference in the object of the present invention. The method for controlling these pests, and the composition and preparation of the corresponding pesticides are described in European Patent Number EP-A-736, 252, and are included as a reference in the object of the present invention.

Claims (11)

1. CLAIMS A method for producing a compound of the formula: and if appropriate, the E / Z isomers, E / Z isomeric mixtures, and / or tautomers thereof, each in free form or in salt form, wherein: R ^ is hydrogen or alkyl of 1 to 4 atoms of carbon; Ra is hydrogen, alkoyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or a radical -CH2B; Het is a heterocyclic aromatic or non-aromatic, monocyclic or bicyclic radical, which is unsubstituted, or depending on the possibilities of replacing the mono- to penta-substituted ring system with substituents selected from the group comprising halogen, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms, haloalkoxy of 1 to 3 carbon atoms, cyclopropyl, halocyclopropyl, alkenyl of 2 to 3 carbon atoms, alkynyl of 2 to 3 carbon atoms, haloalkenyl of 2 to 3 carbon atoms, and haloalkynyl of 2 to 3 carbon atoms, thioalkyl of 1 to 3 carbon atoms, halotioalkyl of 1 to 3 atoms carbon, allyloxy, propargyloxy, thioalyl, thiopropargyl, haloalyloxy, halothioalyl, cyano, and nitro; and B is phenyl, 3-pyridyl, or thiazolyl, which are optionally substituted by one to three substituents from the group comprising alkyl of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms, cyclopropyl, halocyclopropyl, alkenyl 2 to 3 carbon atoms, alkynyl of 2 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, haloalkenyl of 2 to 3 carbon atoms, haloalkynyl of 2 to 3 carbon atoms, haloalkoxy of 1 to 3 atoms of carbon, thioalkyl of 1 to 3 carbon atoms, halotioalkyl of 1 3 carbon atoms, allyloxy, propargyloxy, thioalyl, thiopro-pargyl, haloalyloxy, halothioalyl, halogen, cyano, and nitro; characterized by hydrolyzing a compound of the formula: Q-A-Q (Ha), where A is a direct bond or an organic radical; or of the formula: Q I (iib), Q Q where U is an organic radical; and in the compounds (Ha) and (Hb), Q means wherein Rx, R2, and Het are as defined above for formula (I), and optionally the E / Z isomers, E / Z isomeric mixtures, and / or tautomers thereof, each in free or in the form of salt.
2. 2. The method according to claim 1, for producing a compound of the formula (I) in free form.
3. 3. The method according to claim 1 or 2, for producing a compound of the formula (I), wherein R is hydrogen.
4. 4. The method according to one of claims 1 to 3, for producing a compound of the formula (I), wherein Rj is hydrogen, alkyl of 1 to 3 carbon atoms, or cyclopropyl.
5. The method according to one of claims 1 to 4, for producing a compound of the formula (I) from a compound of the formula (Ha), wherein: A is alkylene of 2 to 20 carbon atoms , alkenylene of 2 to 20 carbon atoms, alkynylene of 2 to 20 carbon atoms, cycloalkylene of 3 to 12 carbon atoms, arylene, or heterocyclylene, straight or branched chain; where the alkylene groups of 2 to 20 carbon atoms, alkenylene of 2 to 20 carbon atoms, alkynylene of 2 to 20 carbon atoms, cycloalkylene of 3 to 12 carbon atoms, arylene, and heterocyclylene, are optionally substituted several times, independently of each other, and the alkylene groups of 2 to 20 carbon atoms, alkenylene of 2 to 20 carbon atoms, and alkynylene of 2 to 20 carbon atoms are optionally interrupted once or several times, independently of each other , by O, NH, or N-alkyl of 1 to 12 carbon atoms, cycloalkylene of 3 to 9 carbon atoms, arylene, or heterocyclylene; or a group -D1-D2-D3-; where D? And D3 'independently of one another, mean cycloalkylene of 3 to 12 carbon atoms or optionally substituted arylene, and D2 means alkylene of 2 to 20 carbon atoms, alkenylene of 2 to 20 carbon atoms, alkynylene of 2 to 20 carbon atoms carbon, O, NH, or N-alkyl of 1 to 12 carbon atoms.
6. The method according to one of claims 1 to 4, for producing a compound of the formula (I) from a compound of the formula (Hb), wherein: U is aryl, heterocyclyl, cycloalkyl of 3 to 12 atoms carbon, or a group: \ Al¬ Ar 1 -X \ / A wherein: i z, and A3, independently of each other, have the same meanings as given in claim 5 for A in the formula (Ha), and X means N or CH.
7. 7. The method according to one of claims 1 to 6, for producing a compound of the formula (I), wherein Het means 2-chloropyrid-5-yl, tetrahydrofuran-3-yl, 5-methyl-tetrahydrofuran-3. ilo, or 2-chlorothiazol-5-yl.
8. The method according to one of claims 1 to 7, for producing a compound of the formula (I), characterized by the pH value being less than 6.
9. The method according to one of claims 1 to 8, for producing a compound of the formula (I), characterized in that it is carried out in water, an alcohol, or a mixture of water with an alcohol.
10. 10. A method to produce a compound of the formula: Q-A-Q (Ha) where A is a direct bond or an organic radical; or of the formula: Q I (Hb) Q Q where U is an organic radical; and in the compounds (Ha) and (IIb), Q means wherein R ^, R2, and Het are as defined in claim 1 for the formula (I), and optionally the E / Z isomers, E / Z isomeric mixtures, and / or tautomers thereof, each in the form free or in salt form, characterized in that a compound of the formula is reacted: (IHb) where A and U have the same meaning as defined for formulas (Ha) and (IIb); T means: and R2 has the same meaning as defined in claim 1 for formula (I); and optionally the E / Z isomers, E / Z isomeric mixtures, and / or tautomers thereof, each in free form or in salt form, when a compound of the formula (Illa) is produced with two equivalents, or when a compound of the formula (IHb) is produced with three equivalents of a compound of the formula: Y- .Het «I (IV) where Rx and Het are defined as in rejovindication 1 for formula (I), and Y is a leaving group.
11. 11. A method for producing a compound of the formula (Illa) or (IHb), as defined in claim 10, characterized in that a compound of the formula is reacted: NH, HaN-A-NH2 (Va), or (Vb), ./Ux H2N NH, and optionally the E / Z isomers, E / Z isomeric mixtures, and / or tautomers thereof, each in free form or in salt form, wherein A and U have the same meaning as defined in claim 1 for the compounds of the formulas (Ha) and (Hb), when a compound of the formula (Illa) is produced with two equivalents, or when a compound of the formula (IHb) is produced with three equivalents of a compound of the formula: where ^ has the same meaning as defined for formula (I), in the presence of an excess of formaldehyde or paraformaldehyde. SUMMARY A method for producing a compound of formula I is described. and if appropriate, the E / Z isomers, E / Z isomeric mixtures, and / or tautomers thereof, each in free form or in salt form, wherein: R is hydrogen or alkyl of 1 to 4 carbon atoms; carbon; R2 is hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or a radical -CH2B; Het is an unsubstituted or substituted heterocyclic radical; and B is phenyl, 3-pyridyl, or thiazolyl, which are optionally substituted; characterized in that a compound of the formula: Q-A-Q (Ha) is hydrolyzed, wherein A is a direct bond or an organic radical; or of the formula:? (Hb), Q Q where U is an organic radical; and in the compounds (Ha) and (Hb), Q means wherein R1 # R2, and Het are as defined above for formula (I), and optionally the E / Z isomers, E / Z isomeric mixtures, and / or tautomers thereof, each in free or in the form of salt; a method for producing the compounds of the formulas (Ha), (Hb), (Illa), and (IHb); as well as a method for controlling pests using the compounds of formulas (Ha) and (Hb). * * * * *