MXPA00007967A

MXPA00007967A - Method for the production of 1,3-disubstituted 2-nitroguanidines

Info

Publication number: MXPA00007967A
Application number: MXPA/A/2000/007967A
Authority: MX
Inventors: Laak Kai Van; Wollweber Detlef
Original assignee: Bayer Ag
Priority date: 1998-02-17
Filing date: 2000-08-15
Publication date: 2001-07-09

Abstract

The invention relates to a method for the production of compounds of formula (I) by reacting compounds of formula (II), wherein Het, R1, R2 and R4 have the meaning cited in the description, with a compound of formula (III) R5-NH2, wherein R5 has the meaning cited in the description.

Description

PROCEDURE FOR THE OBTAINING OF 2-NITROGUANIDINES 1,3- DISSOLVED.

Field of the invention The present invention relates to a new process for the preparation of 1,3-disubstituted 2-nitroguanidines.

BACKGROUND OF THE INVENTION It is known from EP-A-0 483 062 a process for the preparation of 2,3-disubstituted trogaanidines. These are obtained by hydrolysis of the corresponding 2-nitroimino-1,3,5-triazylcyclohexane derivatives. The hydrolysis is preferably carried out in the presence of strong mineral acids or organic acids. The drawback of this method lies in the long reaction times and in the formation of side products, which make expensive purification of the desired final products necessary. Furthermore, when working without the presence of strong acids, it is necessary to take, as is known, measures for the protection, for example, of the reactors REF .: 122375 against corrosion, JP-03 291 267 refers to a similar procedure. DETAILED DESCRIPTION OF THE INVENTION The task of the present invention was to provide an improved process for the preparation of 1,3-di-substituted 2-nitroguanidines. The object of the present invention is a process for obtaining compounds of the formula (I) wherein R 1 signifies hydrogen or alkyl having 1 to 4 carbon atoms, R 2 signifies hydrogen, alkyl having 1 to 6 carbon atoms, cycloalkyl having 3 to 6 carbon atoms or a radical -CH 2 R 3, R 3 signifying alkenyl with 2 to 5 carbon atoms, alkynyl with 2 to 5 carbon atoms, phenyl, cyanophenyl, nitrophenyl, halogen phenyl with 1 to 3 halogen atoms, phenyl substituted by alkyl with 1 to 3 carbon atoms, halogen alkyl with 1 to 3 carbon atoms of 1 to 7 halogen atoms, for alkoxy with 1 to 3 carbon atoms or for-halogenalkoxy with 1 to 3 carbon atoms of 1 to 7 halogen atoms, 3-pyridyl, 5-thiazolyl, 5-thiazolyl substituted for 1 or 2 (preferably 1) substituents of the group consisting of alkyl having 1 to 3 carbon atoms, halogenoalkyl having 1 to 3 carbon atoms with 1 to 7 halogen atoms, cyclopropyl, halogenocyclopropyl, alkenyl having 2 to 3 carbon atoms, alkynyl with 2 to 3 carbon atoms, lcoxy with 1 to 3 carbon atoms, halogenoalkenyl with 2 to 3 carbon atoms with 1 to 4 halogen atoms, halogenalkynyl with 2 to 3 carbon atoms with 1 to 3 halogen atoms, halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, alkylthio with 1 to 3 carbon atoms, halogenalkylthio with 1 to 3 carbon atoms with 1 to 7 halogen atoms, allyloxy, propargyloxy, allythio, propargylthio, haloalyloxy, haloalkylthio, halogen, cyano or nitro; or means 3-pyridyl substituted by 1 to 4 (preferably 1 or 2) moieties of the group consisting of halohaloalkyl having 1 to 3 carbon atoms with 1 to 7 halogen atoms, cyclopropyl, halogenocyclopropyl, alkenyl having 2 to 3 carbon atoms. carbon, alkynyl with 2 to 3 carbon atoms, halogenalkenyl with 2 to 3 carbon atoms with 1 to 4 halogen atoms, halogenalkynyl with 2 to 3 carbon atoms with 1 to 3 halogen atoms, halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, alkylthio with 1 to 3 carbon atoms, halogenalkylthio with 1 to 3 carbon atoms with 1 to 7 halogen atoms, allyloxy, propargyloxy, allylthio, propargthylthio, haloalloyloxy, haloalkylthio, cyano, nitro, alkyl with 1 to 3 carbon atoms, alkoxy with 1 to 3 carbon atoms or halogen, Het means an unsubstituted or substituted, aromatic or non-aromatic, monocyclic or bicyclic radical, preferably a rest of the series formed by which may contain one or two substituents from the group consisting of halogenalkyl having 1 to 3 carbon atoms with 1 to 7 halogen atoms, cyclopropyl, halogenocyclopropyl with 1 to 3 halogen atoms, alkenyl with 2 to 3 carbon atoms, alkynyl with 2 to 3 carbon atoms, halogenalkenyl with 2 to 3 carbon atoms with 1 to 4 halogen atoms, halogenalkynyl with 2 to 3 carbon atoms with 1 to 3 halogen atoms, halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, alkylthio with 1 to 3 carbon atoms, haloalkylthio with 1 to 3 carbon atoms with 1 to 7 halogen atoms, allyloxy, propargyloxy , allylthio, propargthylthio, haloalloyloxy, haloalumylthio, cyano, nitro, alkyl with 1 to 3 carbon atoms, alkoxy with 1 to 3 carbon atoms, and halogen, characterized in that a compound of the formula (II) is reacted wherein R 1, R 2 and Het have the meanings given above and R 4 means, respectively unsubstituted or substituted, alkyl having 1 to 10 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, phenyl, arylalkyl or heterocyclylmethyl, heterocyclyl meaning a heterocycle unsaturated or saturated with 5 or 6 members in the ring with one or more heteroatoms from the group consisting of nitrogen, oxygen, sulfur, such as for example furan, tetrahydrofuran, thiophene or pyridine, optionally in the presence of a diluent, with compounds of the formula (III) R -NH2 (III) wherein R5 means, respectively substituted if appropriate, alkyl, cycloalkyl, aryl, arylalkyl or heterocyclylmethyl, where h-etherscyclyl means an unsaturated or saturated heterocycle with 5 or 6 members on the ring with one or more heteroatoms of the series consisting of nitrogen , oxygen, sulfur, such as for example furan, tetrahydrofuran, thiophene or pyrridine. The compounds of the formula (I) can also be presented as double-bond isomers with respect to the -N = C (2) bond and in their tautomeric forms (formulas la, Ib): Thus the formula (I) is to be understood below in such a way that it also covers the corresponding double-bond isomers and the formulas (la) and (Ib). Surprisingly, the process according to the invention provides selectively and in high yields the final products of the formula (I) after a short reaction time and under mild reaction conditions. If, for example, 1- (2-chloro-thiazo-1-5-ylmethyl) -2-nitro-imino-5-benzyl-3-methyl-1,3,5-triazacyclohexane is used as starting material and benzylamine, it may be used The development of the method according to the invention is represented by means of the following formula scheme: The compounds required as starting materials for the process according to the invention are defined in general by the formula (II). The substituents or preferred ranges of the radicals indicated in the above formulas and which will be mentioned below, are explained in the following manner: Preferably, R 1 is hydrogen, methyl, ethyl, n- or i-propyl, preferably R ^ means hydrogen, methyl, ethyl, n-propyl, i-propyl, or n-butyl, cyclopropyl, cyclopentyl, cyclohexyl or means a moiety -CH2R3, preferably, R3 means alkenyl with 2 to 5 carbon atoms, • alkynyl with 2 to 5 carbon atoms, phenylp, cyanophenyl, nitrophenyl, halogen phenyl with 1 to 3 halogen atoms, phenyl substituted by alkyl with 1 to 3 carbon atoms, halogenalkyl with 1 to 3 carbon atoms and 1 to 7 halogen atoms , by alkoxy with 1 to 3 carbon atoms or by halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, 3-pyridyl, 5-thiazolyl, 5-thiazolyl substituted by 1 to 2 (preferably 1) substituents of the group formed by alquil or with 1 to 3 carbon atoms, halogenalkyl with 1 to 3 carbon atoms with 1 to 7 halogen atoms, cyclopropyl, halogencyclopropyl, alkenyl with 2 to 3 carbon atoms, alkynyl with 2 to 3 carbon atoms, alkoxy with 1 with 3 carbon atoms, halogenalkenyl with 2 to 3 carbon atoms with 1 to 4 halogen atoms, halogenalkynyl with 2 to 3 carbon atoms with 1 to 3 halogen atoms, halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, alkylthio with 1 to 3 carbon atoms, halogenalkylthio with 1 to 3 carbon atoms with 1 to 7 halogen atoms, allyloxy, propargyloxy, allythio, propargylthio, haloalloyloxy, haloaldoxy, halogen, cyano or nitro; or means 3-pyridyl substituted by 1 to 2 (preferably 1) residues of the group consisting of halogenalkyl with 1 to 3 carbon atoms with 1 to 7 halogen atoms, cyclopropyl, halogenocyclopropyl, alkenyl with 2 to 3 carbon atoms, alkynyl with 2 to 3 carbon atoms, halogenalkenyl with 2 to 3 carbon atoms, with 1 to 4 halogen atoms, halogenalkynyl with 2 to 3 carbon atoms with 1 to 3 halogen atoms, halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, alkylthio with 1 to 3 carbon atoms, halogenalkylthio with 1 to 3 carbon atoms with 1 to 7 halogen atoms, allyloxy, propargyloxy, allythio, propargylthio, haloalloyloxy, haloalkylthio, cyano, nitro, alkyl with 1 to 3 carbon atoms, alkoxy with 1 to 3 carbon atoms or halogen, preferably R 4 means alkyl with 1 to 10 carbon atoms, cycloalkyl with 3 to 6 carbon atoms, alkyl with 1 to 10 carbon atoms substituted r 1 to 6 residues of the group consisting of halogen, hydroxy, alkoxy with 1 to 4 carbon atoms, halogenalkoxy with 1 to 4 carbon atoms with 1 to 9 halogen atoms, di- (alkyl with 1 to 4 carbon atoms) -amino or alkoxycarbonyl with 1 to 5 carbon atoms, cycloalkyl with 3 to 6 carbon atoms substituted with 1 to 4 residues of the group consisting of alkyl with 1 to 4 carbon atoms or halogen, phenyl, benzyl or phenyl or benzyl substituted by one to three substituents in the ring of the group consisting of halogen, alkyl having 1 to 4 carbon atoms, halogenoalkyl having 1 to 4 carbon atoms with 1 or 9 halogen atoms, alkoxy with 1 to 4 carbon atoms, halogenoalkoxy with 1 at 4 carbon atoms with 1 to 9 halogen atoms, alkylthio having 1 to 4 carbon atoms, nitro or cyano, or means heterocyclylmethyl, meaning heterocyclyl an unsaturated or saturated heterocycle with 5 or 6 members in the ring with 1 or 2 preferably with 1 (heteroatoms) of the series consisting of nitrogen, oxygen, sulfur such as for example furan, tetrahydrofuran, thiophene or pyridine, preferably, Het means a residue unsubstituted or substituted once or twice (preferably once) of the series formed by especially for the substituents of the series consisting of fluorine, chlorine, bromine, methyl, ethyl, methoxy and ethoxy being chosen, preferably, R5 means alkyl with 1 to 10 carbon atoms, cycloalkyl with 3 to 10 carbon atoms, arylalkyl with 1 to 4 atoms carbon, especially phenylalkyl with 1 to 4 carbon atoms, optionally substituted once or twice, as substituents NH 2, OH, SH, halogen, alkoxy with 1 to 6 carbon atoms, alkylthio with 1 to 6 carbon atoms, alkyl having 1 to 6 carbon atoms and aryl, especially phenyl, or means heterocyclylmethyl, meaning heterocyclyl an unsaturated heterocycle i 0 saturated with 5 or 6 members in the ring with one or two (preferably with one) heteroatoms of the series consisting of nitrogen, oxygen, sulfur such as for example furan, tetrahydrofuran, -thiophene or pyridine. Preferably, Halogen (atom) means F, Cl, Br, I, especially means F, Cl, Br and especially F, Cl.R1 denotes hydrogen, methyl or ethyl, especially preferably R2 means hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, cyclopropyl, cyclopentyl, cyclohexyl or means a -CH2R3 radical, especially preferred, R3 means alkenyl with 2 to 3 carbon atoms, alkynyl with 2 to 3 carbon atoms, phenyl, cyanophenyl, nitrophenyl, halogen phenyl with 1 to 3 halogen atoms, phenyl substituted by alkyl with 1 to 3 carbon atoms, by halogen alkyl with 1 to 3 carbon atoms with 1 to 7 halogen atoms, for alkoxy with 1 to 3 carbon atoms or for halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, means 3-pyrridyl, 5-thiazolyl, means 5-thiazonyl or 3-pyridyl substituted respectively by one or two (preferably by one) substituents of the group consisting of alkyl with 1 to 3 carbon atoms, by halogenalkyl with 1 to 3 carbon atoms with 1 to 7 halogen atoms, for alkoxy with 1 to 3 halogen atoms, for halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, by alkylthio having 1 to 3 carbon atoms, halogenalkylthio having 1 to 3 carbon atoms, 1 to 7 halogen atoms, halogen, cyano or nitro, particularly preferably, R 4 is alkyl with 1 to 10. carbon atoms, cycloalkyl with 3 to 6 át carbon atoms, alkyl with 1 to 8 carbon atoms substituted by 1 to 6 radicals from the group consisting of halogen, by alkoxy with 1 to 4 carbon atoms and by halogenalkoxy with 1 to 4 carbon atoms with 1 or 9 halogen atoms , cycloalkyl with 3 to 6 carbon atoms substituted by one or two radicals of the series consisting of methyl, ethyl, fluorine and chlorine, means phenyl, benzyl, or means phenyl or benzyl substituted respectively by one to three substituents on the ring of the group formed by halogen, by alkyl with 1 to 4 carbon atoms, by halogenalkyl with 1 to 4 carbon atoms with 1 to 9 halogen atoms, for alkoxy with 1 to 4 carbon atoms, for halogenalkoxy with 1 to 4 carbon atoms with 1 to 9 halogen atoms, for alkylthio with 1 to 4 carbon atoms, for nitro or for cyano, or means heterocyclylmethyl, with heterocyclyl meaning an unsaturated or saturated heterocycle with 5 or 6 members in the ring with a heteroatom of the Rie formed by nitrogen, oxygen and sulfur, such as, for example, furan, tetrahydrofuran, thiophene or pyridine, particularly preferably, Het means thiazolyl, pyridyl or tetrahydrofuranyl respectively insubstituted or substituted once or twice (especially once) being chosen the substituents of the series formed by fluorine, for chlorine, methyl and methoxy, particularly preferably R- means alkyl having 1 to 4 carbon atoms, cycloalkyl with 3 to 6 carbon atoms, benzyl or phenylethyl, each optionally substituted from one to five times, as substituents NH 2, OH, Cl, Br, F, alkoxy with 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms, alkyl having 1 to 4 carbon atoms and aryl, especially phenyl, or means heterocyclylmethyl heterocyclyl means an unsaturated or saturated heterocycle with 5 or 6 members in the ring with a heteroatom of the series consisting of nitrogen, oxygen, sulfur such as for example furan, tetrahydrofuran, thiophene or pyridine. Particularly preferably Halogen (atom) means F, Cl, Br, I, especially F, Cl, Br, with F, Cl signifying particularly particularly preferably R 1 is hydrogen, methyl or ethyl, preferably means hydrogen, very particularly preferably R2 means hydrogen, methyl, ethyl, n-propyl, cyclopropyl, cyclopentyl, allyl, propargyl or p-chlorobenzyl, very particularly preferably R4 means methyl, ethyl, n-propyl, cyclopropyl , cyclopentyl, cyclohexyl, phenyl, benzyl or furfurylmethyl, very particularly preferably, Het means one of the remains very particularly preferably, R 5 denotes the corresponding radical R 4 of the compound to be reacted of the formula (II) or the benzyl, NH 2 -CH 2 -CH 2 -, H 0 -CH 2 -CH 2 -, n-hexyl or cyclohexy lo radicals. The compounds of the formula (lia) should be mentioned in a special manner as starting compounds for the process according to the invention. wherein R means methyl, ethyl, cyclopropyl, cyclopentyl, benzyl, or furfurylmethyl, with methyl, benzyl and furfurylmethyl being preferred among these in turn. The compounds of the formula (11b) and (lie) should be mentioned in a special manner as starting materials for the process according to the invention. where R 4 has the meanings indicated above for the compounds of the formula (lia).

With the end products of the process according to the invention, when the compound of the formula (lia) is used, the following compound is obtained when the compound of the formula (Ilb) is used, the following compound is obtained when the compound of the formula (lie) is used, the following compound is obtained The definitions of the remains or the explanations given above in a general manner or in the preferred ranges can be combined arbitrarily with each other, ie even between the corresponding ranges and the preferred ranges. These are valid for the final products as well as, correspondingly, for the starting products and for the intermediate products. Under the designation alkyl, the branched isomers, for example t-butyl for C 4 -alkyl, are also to be understood in this case. Preferably, those compounds of the formula (II) are used in the process according to the invention, in which a combination of the meanings indicated above is preferably present. It is particularly preferred to use those compounds of the formula (II) in the process according to the invention in which a combination of the meanings given above is particularly preferably present.

Very particularly preferably, those compounds of the formula (II) will be used in the process according to the invention, in which a combination of the meanings indicated above is very particularly preferably present. The starting materials of the formula (II) are known or can be prepared according to known processes (see EP-AO 483 062, JP-03 291 267, EP-AO 483 055, EP-AO 428 941, EP-AO 386 565). The compounds of the formula (II) are obtained, for example, if a) a compound of the formula (IV) is reacted with formaldehyde and with a compound of the formula (V) H2N-R (V) and b) the compound obtained from the formula (VI) it is reacted with a compound of the formula (VII) having in the formulas (II) to (VII) the radicals R1, R2, R4 and Het the meanings indicated above and X means a dissociable group. Dissociable groups X may be, for example, halogen, preferably chlorine, bromine or iodine, or sulphonic radicals, such as alkylsulfonic, mesylate or tosylate radicals. The carrying out of step a) of the above process for the preparation of the compounds of the formula (II) is advantageously carried out under normal pressure, if necessary also under higher pressure and, if appropriate, in a suitable solvent and at temperatures comprised between 0 ° C and + 140 ° C, preferably between + 20 ° C and + 120 ° C. As solvents, alcohols, such as methanol, ethanol and propanol, as well as water are preferably suitable. Other suitable solvents are, for example, aromatic hydrocarbons, such as benzene, toluene or xylene; ethers such as tetrahydrofuran, dioxane or diethyl ether; halogenated hydrocarbons such as methylene chloride, chloroform, carbon tetrachloride or chlorobenzene or other solvents, that do not negatively influence the reaction. The solvents can also be used in the form of mixtures. The process step b) of the above process for the preparation of the compounds of the formula (II) can be carried out preferably under normal pressure or under slightly elevated pressure and in the presence of solvents or preferably aprotic diluents. Suitable solvents or diluents are, for example, ethers or compounds of the ethereal type, such as diethyl ether, dipropyl ether, dibutyl ether, dioxane, dimethoxyether or tetrahydrofuran.; aliphatic, aromatic or halogenated hydrocarbons, especially benzene, toluene, xylene, chloroform, methylene chloride, carbon tetrachloride or chlorobenzene; nitriles, such as acetonitrile or propionitrile; dimethylsulfoxide or dimethylformamide. The solvents can also be used in the form of mixtures. This process step s.e. 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 carbonate and potassium carbonate. They can also be used as hydride bases, such as sodium hydride, potassium hydride or calcium hydride. If appropriate, the reaction can also be carried out in the presence of a catalyst, for example of cesium chloride, The starting materials of the formulas (V) and (VII) mentioned above are known and can be obtained commercially or easily prepared in analogy with the known processes The starting products of 2-nitroguanidine of the formula (IV) are likewise known, these can be advantageously prepared from S-methyl-N-nitroisothiourea by reaction with a corresponding primary amine (cf. US Pat. Nos. 4,804,780 and 4,221,802.) N-methyl-N'-nitroguanidine can also be obtained by reaction of nitroguanidine with methylamine (cf. EP-0 798 293) The S-methyl-N is obtained. -nitro? sotiourea with a good yield by nitration of S-methylisourea (see J. Am. Soc. 76, 1877 (1954).) The compounds of the formula (III) are known and can be obtained commercially or can be prepared easily seg a known procedures. Preferably, those compounds of the formula (III) in which R 5 corresponds to the radical R 4 of the compounds to be reacted of the formula (II) will be used. The process according to the invention is carried out, if appropriate, in the presence of a diluent. Suitable diluents are especially organic solvents, especially polar protic solvents, for example alcohols, such as methanol, ethanol, n-propanol, i-propanol, n-butanol or i-butanol and polar aprotic solvents, for example amides such as dimethylformamide, dimethylacetamide or N-methylpyrrolidone or sulfoxides such as dimethyl sulfoxide.

It is also possible to use mixtures of the mentioned diluents. Particularly suitable as diluents are alcohols, especially methanol, ethanol, propanol, i-propanol, n-butanol, i-butanol, sec-butanol. It is also possible to work in a biphasic mixture consisting of water and one of the mentioned diluents. It may be advantageous to add another solvent to the reaction mixture. Suitable as such are ethers, for example dibutyl ether, tetrahydrofuran, dioxane, glycol dimethyl ether or diglycoldimethyl ether, further hydrocarbons, such as benzene, toluene or xylene, halogenated hydrocarbons, such as methylene chloride, chloroform, carbon tetrachloride, chlorobenzene or o-dichlorobenzene, nitriles such as acetonitrile, esters of carboxylic acids such as ethyl acetate or also ketones such as acetone or methylisopropyl ketone. It is also possible to use mixtures of the solvents mentioned. The process according to the invention is carried out at temperatures between 0 ° C and 200 ° C, preferably between 40 ° C and 150 ° C • Preferably, it will be worked under normal pressure, in the case of low-boiling compounds or gaseous of the formula (III) as well as in the case of low boiling point diluents, it is also possible to work under higher pressure. The compounds of the formula (III) are generally reacted in a molar ratio of 0.5: 1 to 10: 1, preferably 1: 1 to 5: 1, based on the starting compound of the formula (II). In general, the reaction will be carried out in such a way that the starting material of the formula (II) and the product are heated. compound of the formula (III) optionally in a diluent and, if appropriate, in the solvent up to the desired temperature. It is also possible to successively dose the compound of the formula (III) in the course of the reaction. For the preparation, it is optionally combined with water, after cooling and the final product is isolated, for example, by filtration or extraction, if appropriate, after concentration by evaporation of the mixture.

Preferably, the reaction will be carried out in a diluent, from which the final product can be directly separated by crystallization by cooling the reaction mixture and can be isolated easily, for example by filtration. Suitable diluents are alcohols, especially methanol, ethanol, propanol, i-propanol, isobutanol, n-butanol, sec-butanol. It is also possible to carry out an anhydrous production of the reaction mixture by distilling off the diluent and, if necessary, the solvent after the reaction has ended and extracting the remaining residue with a suitable extraction agent. Suitable extraction agents are basically all solvents which are inert towards the final products, in which the final products are sufficiently soluble. These include, for example, aliphatic hydrocarbons such as n-pentane, n-hexane, cyclohexane, halogenated aliphatic hydrocarbons, such as methylene chloride or chloroform, aromatic hydrocarbons such as benzene, toluene or xylene, halogenated aromatic hydrocarbons such as chlorobenzene. or odochlorobenzene or also ethers such as for example ethyl tert-butyl ether. The final products are separated by crystallization, optionally after concentration by evaporation of the extraction agent and can be isolated by filtration, or the extraction agent is completely or almost completely removed and the residue, if necessary, is purified, for example by recrystallization . The compounds prepared according to the invention of the formula (I) are valuable active ingredients in the fight against pests. Especially the compounds of the formula (I) "are suitable for the control of insects and arachnids, which occur in useful and ornamental plants in agriculture, especially in cotton, vegetable and fruit tree plantations, in forestry, in the protection of stored products and materials, as well as in the hygiene sector, especially for domestic and useful animals (see, for example, EP-AO 376 279, EP-AO 375 907, EP-AO 383 091 ).

EXAMPLES Example 1. Obtaining 1- (2-chlorothiazol-5-ylmethyl) -2-nitro-3-methylguani.dina. a) 39 g of 1- (2-chlorothiazol-5-ylmethyl 2-nitro-imino-5-benzyl-3-methyl-1,3,5-triazacyclohexane are heated. and 16.5 g of benzylamine in 200 ml of isobutanol for 3 hours at 95 ° C to 100 ° C. It is cooled to 20 ° C, stirring is continued for 1 hour at 20 ° C and the product is isolated by filtration. The crystallized product is washed with water and then dried. Yield 22 g, HPLC: 95%. The product is, according to its chromatographic and spectroscopic data, identical with another authentic sample, obtained by another route, of 1- (2-chlorothiazol-5-ylmethyl) -2-nitro-3-methylguanidine. b) 39 g of 1- (2-chlorothiazol-5-ylmethyl) -2-nitro-imino-5-benzyl-3-methyl-1,3,5-triaza-cyclohexane and 3.6 g of ethylenediamine in 200 ml are heated. of isobutanol for 2 hours at 95-100 ° C. It is cooled to 20 ° C, stirring is continued for 1 hour at 20 ° C and the product is isolated by filtration. The crystalline product is washed with water and then dried. Yield 21.7 g. The product is identical, according to its chromatographic data, with an authentic sample, obtained by another route, of 1- (2-chlorothiazol-5-ylmethyl) -2-nitro-3-methylguanidin. c) 4 g of 1- (2-chlorothiazol-5-ylmethyl) -2-nitro-imino-5-benzyl-3-methyl-1,3,5-triazacyclohexane and 2 g of aminoethanol in 20 ml of isobutanol are heated. for 2 hours at 110 ° C.

The controls of the reaction by thin layer chromatography show complete conversion to give 1- (2-chlorothiazol-5-ylmethyl) -2-nitro-3-methyl guanidine. d) 38.4 g of 1- (2-chlorothiazol-5-ylmethyl) -2-nitro-imino-5-benzyl-3-methyl-1,3,5-triazacyclohexane and 12.1 g of n-hexylamine in 200 ml are heated. of n-butanol for 2 hours at 95-100 ° C. The controls of the reaction by thin layer chromatography show complete conversion to give 1- (2-chlorothiazol-5-ylmethyl) -2-nitro-3-methylguanidine. e) 39.2 g of 1- (2-chlorothiazol-5-ylmethyl) -2- or tro-imino-5-benzyl-3-met il-1,3,5-triazacyclohexane and 11.9 g of cyclohexylamine are heated in 200 ml of isobutanol for 4 hours at 95-100 ° C. The controls of the reaction by thin layer chromatography show complete conversion to give 1- (2-chlorothiazol-5-ylmethyl) -2-nitro-3-methylguanidine. f) 76 g of 1- (2-chlorothiazol-5-ylmethyl) -2-nitro-imino-5-benzyl-3-methyl-1,3,5-triazacyclohexane are placed in 150 ml of methanol. The mixture is heated to 65 ° C. and 32 g of benzylamine are metered in over the course of one hour. Stir for a further 4 hours at 65 ° C. It is cooled to 0 ° C, stirred for an additional hour at 0 ° C and the product isolated by filtration. The crystalline product is washed with cold methanol and then dried. Yield 40 g, HPLC: 99% The product is, according to its chromatographic and spectroscopic data, identical with an authentic sample, obtained by another route, of 1- (2-chlorothiazol-5-ylmethyl) -2-nitro-3-methylguanidine . The compounds of the formula (I) indicated in the following table can also be obtained analogously: Table Example Het Rl R2 Table (Continued) Example Het R 'R2 no Table (Continued) Example Het R > R2 not H-CH2-CH = CH2 Table (Continued) Example Het R »R = no O 35 L CH, CH3 It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention is that which is clear from the present description of the invention. Having described the invention as above, property is claimed as contained in the following:

Claims

R E I V I N D I C A C I O N S 1- Procedure for obtaining compounds of the formula. (I) wherein R 1 signifies hydrogen or alkyl having 1 to 4 carbon atoms, R 2 signifies hydrogen, alkyl having 1 to 6 carbon atoms, cycloalkyl having 3 to 6 carbon atoms or a radical -CH 2 R 3, R 3 signifying alkenyl with 2 to 5 carbon atoms, alkynyl with 2 to 5 carbon atoms, phenyl, cyanophenyl, nitrophenyl, halogen phenyl with 1 to 3 halogen atoms, phenyl substituted by alkyl with 1 to 3 carbon atoms, halogen alkyl with 1 to 3 carbon atoms with 1 to 7 halogen atoms, by alkoxy with 1 to 3 carbon atoms or by halogenalkoxy with 1 to 3 carbon atoms and 1 to 7 halogen atoms, 3-pyridyl, 5-thiazolyl, 5-thiazolyl substituted by 1 or 2 (preferably by 1) substituents of the group consisting of alkyl with 1 to 3 carbon atoms, halogenoalkyl with 1 to 3 carbon atoms with 1 to 7 halogen atoms, cyclopropyl, halogenocyclopropyl, alkenyl with 2 to 3 carbon atoms, alkynyl with 2 to 3 carbon atoms, alkoxy with 1 to 3 carbon atoms, haloalkenyl with 2 to 3 carbon atoms with 1 a 4 halogen atoms, halogenalkynyl with 2 to 3 carbon atoms with 1 to 3 halogen atoms, halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, alkylthio with 1 to 3 carbon atoms, halogenalkylthio with 1 to 3 carbon atoms with 1 to 7 halogen atoms, allyloxy, propargyloxy, allythio, propargylthio, haloalyalloxy, haloalkylthio, halogen, cyano or nitro; or means 3-pyridyl substituted by 1 to 4 (preferably by

1 or 2) remains of the group consisting of halogenalkyl having 1 to 3 carbon atoms with 1 to 7 halogen atoms, cyclopropyl, halogenocyclopropyl, alkenyl having 2 to 3 carbon atoms, alkynyl with 2 to 3 carbon atoms, halogenalkenyl with 2 to 3 carbon atoms with 1 to 4 halogen atoms, halogenalkynyl with 2 to 3 carbon atoms with 1 to 3 halogen atoms, halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, alkylthio with 1 to 3 carbon atoms, halogenalkylthio with 1 to 3 carbon atoms with 1 to 7 halogen atoms, allyloxy, propargyloxyallylthio, propargyl thio, haloalloyloxy, haloalkylthio, cyano, nitro, alkyl with 1 to 3 carbon atoms, alkoxy with 1 to 3 carbon atoms or halogen, Het means an unsubstituted or substituted, aromatic or non-aromatic, monocyclic or bicyclic moiety, preferably a residue from the series consisting of What? ii N? p-Vp-pi-n which can contain one or two substituents from the group consisting of halogenalkyl having 1 to 3 carbon atoms with 1 to 7 halogen atoms, cyclopropyl, halogenocyclopropyl with 1 to 3 halogen atoms, alkenyl with 2 to 3 carbon atoms, alkynyl with 2 to 3 carbon atoms, halogenalkenyl with 2 to 3 carbon atoms with 1 to 4 halogen atoms, halogenalkynyl with 2 to 3 carbon atoms with 1 to 3 halogen atoms, halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, alkylthio with 1 to 3 carbon atoms, halogenalkylthio with 1 to 3 carbon atoms with 1 to 7 halogen atoms, allyloxy, propargyloxy, allylthio, propargthylthio, haloalloyloxy, haloalumylthio, cyano, nitro, alkyl with 1 to 3 carbon atoms, alkoxy with 1 to 3 carbon atoms, and halogen, characterized in that a compound of the formula (II) is reacted wherein R 1, R 2 and Het have the meanings given above and R 4 means, respectively unsubstituted or substituted, alkyl having 1 to 10 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, phenyl, arylalkyl or heterocyclylmethyl, heterocyclyl meaning a heterocycle unsaturated or saturated with 5 or 6 members in the ring with one or more heteroatoms from the group consisting of nitrogen, oxygen, sulfur, such as for example furan, tetrahydrofuran, thiophene or pyridine, optionally in the presence of a diluent, with compounds of the formula (III) R5-NH2 (III) in which R5 means, optionally substituted, alkyl, cycloalkyl, aryl, arylalkyl or heterocyclylmethyl, meaning heterocyclyl an unsaturated or saturated heterocycle with 5 or 6 members in the ring with one or several heteroatoms of the series consisting of nitrogen, oxygen, sulfur, such as for example furan, tetrahydrofuran, thiophene or pyridine.

2 . - Process according to claim 1, characterized in that the formulas (I), (II) and (III) according to claim 1, R1 means hydrogen, methyl, ethyl, n- or i-propyl, R 'means hydrogen, methyl, ethyl, n-propyl, i-propyl, or n-butyl, cyclopropyl, cyclopentyl, cyclohexyl or means a moiety -CH2R3, R3 means alkenyl with 2 to 5 carbon atoms, alkynyl with 2 to 5 carbon atoms, phenyl, cyanophenyl, nitrophenyl, halogen phenyl with 1 to 3 halogen atoms, phenyl substituted by alkyl with 1 to 3 carbon atoms, by halogen alkyl with 1 to 3 carbon atoms and 1 to 7 halogen atoms, by alkoxy with 1 to 3 carbon atoms or by halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, 3-pyridyl, 5-thiazolyl, 5-thiazolyl substituted by 1 to 2 (preferably 1) substituents of the group formed by alkyl with 1 to 3 carbon atoms, halogenoalkyl with 1 to 3 carbon atoms with 1 to 7 halogen atoms, cyclopropyl, halogenocyclopropyl, alkenyl with 2 to 3 carbon atoms, alkynyl with 2 to 3 carbon atoms, alkoxy with 1 to 3 carbon atoms, halogenalkenyl with 2 to 3 carbon atoms with 1 to 4 halogen atoms, halogenoalkynyl with 2 to 3 carbon atoms with 1 to 3 halogen atoms, halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, alkylthio with 1 to 3 carbon atoms, halogenalkylthio with 1 to 3 carbon atoms with 1 to 7 halogen atoms, allyloxy, propargyloxy, allythio, propargylthio, haloalyloxy, haloalkylthio, halogen, cyano or nitro; or means 3-pyridyl substituted by 1 to 2 (preferably 1) residues of the group consisting of halogenalkyl with 1 to 3 carbon atoms with 1 to 7 halogen atoms, cyclopropyl, halogenocyclopropyl, alkenyl with 2 to 3 carbon atoms, alkynyl with 2 to 3 carbon atoms, halogenalkenyl with 2 to 3 carbon atoms, with 1 to 4 halogen atoms, halogenalkynyl with 2 to 3 carbon atoms with 1 to 3 halogen atoms, halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, alkylthio with 1 to 3 carbon atoms, halogenalkylthio with 1 to 3 carbon atoms with 1 to 7 halogen atoms, allyloxy, propargyloxy, allythio, propargylthio, haloalloyloxy, haloalkylthio, cyano, nitro, alkyl with 1 to 3 carbon atoms, alkoxy with 1 to 3 carbon atoms or halogen, R4 means alkyl with 1 to 10 carbon atoms, cycloalkyl with 3 to 6 carbon atoms, alkyl with 1 to 10 carbon atoms substituted for 1 to 6 remains of group consisting of halogen, hydroxy, alkoxy with 1 to 4 carbon atoms, halogenalkoxy with 1 to 4 carbon atoms with 1 to 9 halogen atoms, di- (alkyl with 1 to 4 carbon atoms) -amino or alkoxycarbonyl with 1 at 5 carbon atoms, cycloalkyl with 3 to 6 carbon atoms substituted with 1 to 4 radicals of the group consisting of alkyl with 1 to 4 carbon atoms or halogen, means phenyl, benzyl or means phenyl or benzyl substituted by one to three substituents on the ring of the group consisting of halogen, alkyl with 1 to 4 carbon atoms, halogenalkyl with 1 to 4 carbon atoms with 1 or 9 halogen atoms, alkoxy with 1 to 4 carbon atoms, halogenalkoxy with 1 to 4 carbon atoms with 1 to 9 halogen atoms, alkylthio having 1 to 4 carbon atoms, nitro or cyano, or means heterocyclylmethyl, with heterocyclyl being an unsaturated or saturated heterocyclic group having 5 or 6 members in the ring with 1 or 2, preferably with 1 (heteroatoms) of the series consisting of nitrogen, oxygen, sulfur such as for example furan, tetrahydrofuran, thiophene or pyridine, Het means a residue unsubstituted or substituted once or twice (preferably once) of the series formed by especially for the substituents of the series consisting of fluorine, chlorine, bromine, methyl, ethyl, methoxy and ethoxy being chosen; R5 means alkyl with 1 to 10 carbon atoms, cycloalkyl with 3 to 10 carbon atoms, arylalkyl with 1 to 4 carbon atoms, especially phenylalkyl with 1 to 4 carbon atoms, optionally substituted one or two times, as substituents NH2, OH, SH, halogen, alkoxy with 1 to 6 carbon atoms, alkylthio with 1 to 6 carbon atoms. carbon, alkyl having 1 to 6 carbon atoms and aryl, especially phenyl, R 5 signifies heterocyclylmethyl, meaning heterocyclyl an unsaturated or saturated heterocycle with 5 or 6 members in the ring with one or two (preferably with one) heteroatoms of the series consisting of nitrogen, oxygen, sulfur such as for example furan, tetrahydrofuran, thiophene or pyridine,

3. Process according to claim 1, wherein in the formulas (I), (II) and (III) according to claim 1, R1 means hydrogen, methyl, ethyl, R2 means hydrogen, methyl, ethyl, n-propyl, i-propyl, n-butyl, cyclopropyl, cyclopentyl, cyclohexyl or means a radical -CH2R3, R3 means alkenyl with 2 to 3 carbon atoms, ilo with 2 to 3 carbon atoms, phenyl, cyanophenyl, nitrophenyl, halogen phenyl with 1 to 3 halogen atoms, phenyl substituted by alkyl with 1 to 3 carbon atoms, halogen alkyl with 1 to 3 carbon atoms and 1 to 7 atoms of halogen, by alkoxy with 1 to 3 carbon atoms or by halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, means 3-pyridyl, 5-thiazolyl, means 5-thiazonyl or 3-pyridyl substituted respectively by one or two (preferably by one) substituents of the group consisting of alkyl with 1 to 3 carbon atoms, by halogen alkyl with 1 to 3 carbon atoms with 1 to 7 halogen atoms, for alkoxy with 1 to 3 halogen atoms, for halogenalkoxy with 1 to 3 carbon atoms with 1 to 7 halogen atoms, for alkylthio with 1 to 3 carbon atoms, halogenalkylthio with 1 to 3 carbon atoms with 1 to 7 halogen atoms, for halogen, cyano or nitro, R4 means alkyl with 1 to 10 carbon atoms, cycloalkyl with 3 to 6 carbon atoms, alkyl with 1 to 8 carbon atoms substituted by 1 to 6 radicals of the group consisting of halogen, alkoxy with 1 to 4 carbon atoms and halogenalkoxy with 1 at 4 carbon atoms with 1 or 9 halogen atoms, cycloalkyl with 3 to 6 carbon atoms substituted by one or two residues of the series consisting of methyl, ethyl, fluorine and chlorine, means phenyl, benzyl or means phenyl or substituted benzyl respectively by one to three substituents on the ring of the group consisting of halogen, for alkyl having 1 to 4 carbon atoms, for halogenalkyl with 1 to 4 carbon atoms with 1 to 9 halogen atoms, for alkoxy with 1 to 4 carbon atoms, by halogenalkoxy with 1 to 4 carbon atoms with 1 to 9 halogen atoms, for alkylthio having 1 to 4 carbon atoms, per nltro or per cyano, or means heterocyclylmethyl, meaning heterocyclyl an unsaturated or saturated heterocycle with 5 or 6 members in the ring with a heteroatom of the series consisting of nitrogen, oxygen and sulfur, such as for example furan, tetrahydrofuran, thiophene or pyridine, Het means thiazolyl, pyridyl or tetrahydrofuranyle respectively unsubstituted or substituted once or twice (especially once) being chosen the substituents of the series consisting of fluorine, chlorine, methyl and methoxy, R5 means alkyl having 1 to 4 carbon atoms, cycloalkyl having 3 to 6 carbon atoms, benzyl or phenylethyl or, respectively, substituted one to five times, as substituents NH2, OH, Cl, Br, F, alkoxy with 1 to 4 carbon atoms, alkylthio having 1 to 4 carbon atoms, alkyl with 1 to 4 carbon atoms and aryl, especially phenyl, or R 5 means heterocyclylmethyl, with heterocyclyl meaning an unsaturated or saturated heterocycle with 5 or 6 members in the ring with a heteroatom of the series consisting of nitrogen, oxygen, sulfur such as for example furan , tetrahydrofuran, thiophene or pyridine,

4. Process according to claim 1, characterized in that in the formulas (I), (II) and (III), R1 means hydrogen, methyl or ethyl, preferably means hydrogen, R2 means hydrogen, methyl , ethyl, n-propyl, cyclopropyl, cyclopentyl, allyl, propargyl or p-chlorobenzyl, R4 means methyl, ethyl, n-propyl, cyclopropyl, cyclopentyl, cyclohexyl, phenyl, benzyl or furfurylmethyl, Het means one of the residues R5 means the corresponding radical R4 of the compound to be reacted of the formula (II) or the benzyl radicals, NH2-CH2-CH2-, HO-CH2-CH2-, n-hexyl or cyclohexyl.

5. Process according to claim 1, for obtaining a compound of the formula characterized in that a compound of the formula (lia) is reacted if appropriate in the presence of a diluent with a compound of the formula (III) R -NH 2 in which R 4 = R 5 means methyl, ethyl, cyclopropyl, cyclopentyl benzyl or furfurylmethyl.

6. Process according to claim 1, for obtaining a compound of the formula characterized in that a compound of the formula (Ilb) is reacted if appropriate in the presence of a diluent with a compound of the formula (III) R5-NH2 where R4 = R5 means methyl, ethyl, cyclopropyl, cyclopentyl benzyl or furfurylmethyl. 7 - Process according to claim 1 for obtaining a compound of the formula characterized in that a compound of the formula (lie) is reacted if appropriate in the presence of a diluent with a compound of the formula (III) R5-NH2 where R4 = R ° means methyl, ethyl, cyclopropyl, cyclopentyl benzyl or furfurylmethyl. 8. Process according to claim 1, characterized in that the reaction is carried out in the absence of a diluent. 9. Process according to claim 1, characterized in that the reaction is carried out in the presence of a diluent of the series of alcohols. 10. Process according to claim 1, characterized in that it is carried out at a temperature comprised between 0 ° C and 200 ° C.