MXPA00009107A - Process for the preparation of nitroguanidine derivatives - Google Patents

Abstract

A process for the production of a compound of formula (I), wherein R1 is hydrogen or C1-C4-alkyl;R2 is hydrogen, C1-C6-alkyl, C2-C6-alkenyl, C2-C6-alkinyl, C3-C6-cycloalkyl or a radical -CH2B;A is an unsubstituted or mono- to penta-substituted aromatic or non-aromatic, monocyclic or bicyclic heterocyclic radical;and B is phenyl, 3-pyridyl or thiazolyl, which are optionally substituted by one to three substituents, is described;characterised in that a compound of formula (II), wherein R1, R2 and A have the same significances as in formula (I), and X is O or S;is hydrolysed with a strong acid. The compounds of formula (I) are suitable for the preparation of pesticides. The intermediates (II) are claimed.

Description

PROCESS FOR THE PREPARATION OF NITROGUANIDINE DERIVATIVES The invention relates to a process for the production of a compound of the formula: wherein: Ri is hydrogen or alkyl of 1 to 4 carbon atoms, - R2 is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or a -CH2B radical; A is a heterocyclic, monocyclic or bicyclic, aromatic or non-aromatic, unsubstituted radical, or - depending on the possibilities of substitution of the ring system -, one of which is mono- to penta-substituted by substituents selected from 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 ha-loalkynyl of 2 to 3 carbon atoms, thioalkyl of 1 to carbon atoms, halotioalkyl of 1 to 3 carbon atoms allyloxyl, propargiloxyl, thioalyl, thiopropargyl, haloalyl xyl, halothioalyl, cyano, and nitro; and B is phenyl, 3-pyridyl or thiazolyl, which are optionally substituted by 1 to 3 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, alkoxyl of 1 to 3 carbon atoms, haloalkenyl of 2 to 3 carbon atoms, haloalkynyl of 2 to carbon atoms, haloalkoxy of 1 to 3 carbon atoms, thioalkyl of 1 to 3 carbon atoms, halotioalkyl of 1 to carbon atoms, allyloxy, propargyloxy, thioalyl, thiopro pargyl, haloalyloxy, halothioalyl, halogen, cyano, and nitro; and optionally the possible E / Z isomers, E / Z isomeric mixtures, and / or tautomers thereof, respectively free form or salt form; characterized in that a compound of the formula: wherein Ri, R2, and A have the same meanings as the formula (I), and X is O or S; It is hydrolyzed with a strong acid. The compounds of the formula (I) can exist as E / Z isomers, for example in the following two isomeric forms In accordance with the above, where reference is made hereinafter to the compounds of the formula (I) it is understood that this also applies to the corresponding E / Z isomers, even when the latter are not mentioned specifically in each case. case. The compounds of the formula (I) can also exist in part as tautomers, for example in the forms: According to the above, where reference is made hereinabove and hereinafter to the compounds of the formula (I), it is understood that this also applies to the corresponding tautomers, even when the latter are not specifically mentioned. in each case. The compounds of the formula (I), and optionally their E / Z isomers and tautomers, can exist as salts. The co-positions 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 hydrohalic acid, with strong organic carboxylic acids, such as alkanocarboxylic acids of 1 to 4 carbon atoms which are optionally substituted , for example by halogen, for example acetic acid, such as optionally unsaturated dicarboxylic acids, for example oxalic acid, malonic acid, maleic acid, fumaric acid, or phthalic acid, such as hydroxycarboxylic acids, for example ascorbic acid, lactic acid, acid malic, tartaric acid, or citric acid, or such as benzoic acid, or with organic sulfonic acids, such as alkanesulfonic acids of 1 to 4 carbon atoms or arylsulfonic acids which are optionally substituted, for example by halogen, for example methanesulfonic or p-toluenesulfonic acid. The salts of the compounds of the formula (I) with acids of the above mentioned types are obtained during the processing of the reaction mixtures. In addition, 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, such as alkali metal salts 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 with a mono-, di-, or tri-hydroxyalkylamine lower, for example mono-, di-, or triethanolamine. In addition, if required, the corresponding internal salts can be formed. Within the scope of the invention, the agrochemically convenient salts are preferred. Where the free compounds of the formula (I) or their salts are referred to hereinbefore and subsequently herein, it is understood that this also applies to the corresponding salts or to 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 their salts. The free form is preferred. In the definition of the present formulas (I) and (II), the individual generic terms are to be understood as follows: The halogen atoms considered as substituents are fluorine and chlorine, and also bromine and iodine, where fluorine is preferred, chlorine, and bromine, especially chlorine. Here, halogen is understood to be an independent substituent or part of a substituent such as in haloalkyl, halothioalkyl, haloalkoxy, halocycloalkyl, haloalkenyl, haloalkynyl, haloalyloxy, or halothioallyl. The alkyl, thioalkyl, alkenyl, alkynyl, and alkoxy radicals considered as substituents can be straight or branched chain. Examples of these alkyls 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 their isomers. Thioalkyl is, for example, thiomethyl, thioethyl, isothiopropyl, thiopropyl, or isomeric thiobutyl. If the alkyl, alkoxy, alkenyl, alkynyl, or cycloalkyl groups considered as substituents are substituted by halogen, they can only be partially or even perhalogenated. The aforementioned definitions apply to halogen, alkyl, and alkoxy. Examples of the alkyl elements of these groups are methyl which is mono- to trisubstituted by fluorine, chlorine, and / or bromine, for example CHF2 or CF3; ethyl which is mono- to penta-substituted by fluorine, chlorine, and / or bromine, for example CH2CF3, CF2CF3 CF2CC13, CF2CHC12, CF2CHF2, CF2CFC12;, CF2CHBr2, CF2CHCIF, CF2CHBrF or CCIFCHCIF; propyl or isopropyl which is mono- to hepta-substituted by fluorine, chlorine, and / or bromine, for example CH2CHBrCH2Br, CF2CHFCF3, CH2CF2CF3 or CH (CF3) 2; butyl which is mono- to nona-substituted by fluorine, chlorine, and / or bromine, or one of its isomers, for example CF (CF3) CHFCF3 or CH2 (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, alkoxy, or cycloalkyl groups are substituted by other substituents, they can be substituted one or more times by the same or different substitutes of those listed. Preferably, one or two additional substituents are present in the substituted groups. Cycloalkyl radicals considered as substituents are, 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, propargyloxyl, thioalkyl, or thiopropargyl are separated from the site of linking to the heteroatom (O or S) preferably by a saturated carbon atom. It is already known that, to produce 1,3-disubstituted 2-nitroguanidines, an additional substituent (eg by alkylation) can be introduced into the mo-substituted-2-nitroguanidines (see, for example, European Patent Applications Nos. 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 starting material in these reactions, the proposed substitution reactions of this class are often not selective, and lead to substitution products. unwanted The aforementioned European Patent Applications describe the preparation of 1,3-disubstituted 2-nitroguanidines by the reaction of monosubstituted nitroisothioureas with primary amines while the mercaptan is dissociated. However, these nitroisothiourea compounds contain thioalkyl leaving groups, and are proposed as starting compounds in the known processes, which can only be obtained with difficulty. In addition, in the European Patent Number EP-A-0, 483, 062, a process for the preparation of the compounds of the formula (I) is described, wherein a triaza compound is hydrolyzed. This process can not be completely satisfactory in particular for ecological reasons. It is now shown that the processes described above for the preparation of the compounds of the formula (I) do not meet the requirements with respect to purity and yield, for which reason, there is a need to provide an improved process for the preparation of these compounds from starting compounds that can be easily obtained. Now, in a surprising way, it has been found that the process according to the invention can satisfy these requirements. The hydrolysis process according to the invention is preferably carried out at a pH value of 2 or lower, under normal pressure, and at a temperature of 0 ° C. at 120 ° C, preferably from 50 ° C to 100 ° C. It is preferable to operate in a mineral acid, especially hydrochloric acid, hydrobromic acid, sulfuric acid, or phosphoric acid, or in aqueous solutions of alkylcarboxylic acids, halogenated alkylcarboxylic acids, and sulfonic acids, especially in concentrated hydrochloric acid. The reaction is carried out in a solvent or diluent that is inert toward the reaction components. Suitable solvents are, in particular, alcohols, such as methanol, ethanol, propanol, and isopropanol, and 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. Preferably, a compound of the form-mule (II) is hydrolyzed in an aqueous medium or in a mixture of water with an alcohol. The process according to the invention preferably serves to produce compounds of the formula (I) wherein the heterocyclic radical A is unsaturated and is linked by means of a carbon atom as a ring member with the basic substance. Preferred A radicals are pyridyl, thiazolyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, n-oxide-pyridinium, oxazolyl, isoxazolyl, thienyl, morpholinyl, piperidinyl, pyridinyl, and pyrazinyl.; more preferably pyridyl, thiazolyl, tetrahydrofuranyl, and n-oxide-pyridinium, especially 3-pyridyl, 2-halopyrid-5-yl, 2,3-dihalopyrid-5-yl, 2-halothiazol-5-yl, tetrahydrofuran-3-yl, 5-methyl-tetrahi-drofuran-3-yl, l-oxopyrid-3-yl, l-oxo-2-halopyrid-5-yl, and 1-oxo-2,3-dihalopyrid-5 -ilo. In the same way, it is preferable that the heterocycles A carry 1 to 3 substituents which are selected from the group comprising halogen, alkyl of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms, haloalkoxy of 1 to 3 carbon atoms, and alkoxy of 1 to 3 carbon atoms. In addition, compounds of the formula (I) according to the invention are preferably produced, wherein the radical B is a phenyl, pyridyl, and thiazolyl radical which is unsubstituted or which may be substituted by 1 to 2 selected radicals. from the group comprising halogen, alkyl of 1 to 3 carbon atoms, haloalkyl of 1 to 3 carbon atoms, haloalkoxy of 1 to 3 carbon 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, those in which Ri is hydrogen, R2 is methyl, ethyl, normal propyl, normal butyl, allyl, propargyl, or cyclopropyl, and is pyridyl, 1-oxopyridyl, tetrahydrofuranyl, thiazolyl, or is pyridyl, 1-oxidepyridinium, tetrahydrofuranyl, and thiazolyl, which is substituted by 1 to 3 substituents selected from the group comprising halogen, alkyl of 1 to 3 carbon atoms, carbon, haloalkyl of 1 to 3 carbon atoms, haloalkoxy of 1 to 3 carbon atoms, and alkoxy of 1 to 3 carbon atoms. In this regard, the production of the compounds of the formula (I) wherein: a) Ri is hydrogen is also of interest; b) R2 is methyl; c) A is 2-chloropyrid-5-yl, tetrahydrofuran-3-yl, 2-methyltetrahydrofuran-4-yl, or 2-chlorothiazol-5-yl; and d) X is O. The compounds of the formula (I) produced according to the invention are valuable active ingredients in the control of pests, while they are tolerated by mammals, fish, and plants. The compounds of the formula (I) are especially suitable for the control of insects and arachnids, as they are present in crop and ornamental plants in agriculture especially in cotton, vegetable and fruit plantations, in forests, and in the protection of warehouses. and materials, as well as in the hygiene sector, particularly for domestic and farm animals. The compounds are particularly effective against sucking insects that damage plants, especially aphids and grasshoppers. The pesticidally substituted 2-nitroguanidines of the type that can be produced according to the invention are described, for example, in European Patent Applications Nos. 376,279; 375.907, and 383, 091.

The starting compounds or starting materials of the formula (II) which can be considered for the process according to the invention are partially known or can be produced by known processes. Where they are new, it simulates an objective of the invention. Table C: Compounds of the formula: R1 NN N02 Table 1; Compounds of the general formula (lia), wherein A is and Ri R2 / and X each correspond to any of the lines of Table C. Table 2; Compounds of the general formula (lia), wherein A is < N-r 'and Ri, R2 / and X each correspond to any of the lines in Table C. Table 3: Compounds of the general formula (lia), where A is "Xr and Ri, R2, and X each one corresponds to any of the lines in Table C ..- Table 4: Compounds of the general formula (lia), where A is and Ri, R2, and X each correspond to any of the lines in Table C. Table 5: Compounds of the general formula (lia), where A is and Rl7 R2, and X each correspond to any of the lines in Table C. Ta la 6: Compounds of the general formula (lia), where A e Cr and Ri, R2, and X each correspond to any of the lines in Table C. Table 7: Compounds of the general formula (lia), where A is and Ri, R2, and X each correspond to any of the lines in Table C. Table 8: Compounds of the general formula (lia), where A is and Ri R2 / and each correspond to any of the lines in Table C. Table 9; Compounds of the general formula (lia), wherein A is and Ri, R2, and X each correspond to any of the lines in Table C. Table 10: Compounds of the general formula (lia), where A is Ri, R2, and X each correspond to any of the lines in Table C, Table 11: Compounds of the general formula (lia), where A is and Ri, R2, and X each correspond to any of the lines in Table C. Table 12: Compounds of the general formula (lia), where A is and Ri, R2, and X each correspond to any of the lines in Table C.

Preparation Examples Example 1; Preparation of 1- (2-chloropyrid-5-ylmethyl) -2-nor rp-3-methyl-guani ina A mixture of 4.0 grams of 5- (2-chloropyrid-5-ylmethyl) -3-methyl-4-nitroimino -perhydro-l, 3, 5-oxadiazine and 20 milliliters of concentrated hydrochloric acid, is stirred for 2 hours at 80 ° C. The reaction mixture is cooled to 5 ° C, adjusted to a pH of about 5 with a concentrated caustic soda solution, and filtered. The filtrate residue is mixed with diethyl ether / ethyl acetate, 1: 1, and filtered again. The title compound is obtained from this mill.

Example 2; Preparation ÚS 1- (2-Chlorothiazol-5-ylmethyl) -2-nitro-3-methyl-guanidine A mixture of 5.0 grams of 5- (2-chlorothiazol-5-ylmethyl) -3-methyl-4-nitroimino-perhydro-l , 3, 5-oxadiazine and 20 milliliters of concentrated hydrochloric acid, is stirred for 2 hours at 80 ° C. The reaction mixture is cooled to 5 ° C, adjusted to a pH of about 5 with concentrated caustic soda solution. , and it filters. The filtrate residue is mixed with 1: 1 diethyl ether / ethyl acetate (volume: volume) and filtered again. In this way, the title compound is obtained.

The following compounds of the formula (I) listed in Table 13 can also be obtained in a manner analogous to the above procedures described in Examples 1 and 2. c-propyl is cyclopropyl.

Table 13: Compounds of the formula (I) _ 13. 1 2-chloro-pyrid-5-yl HH 13.2 2-chloro-pyrid-5-yl H -CH3 13.3 2-chloro-pyrid-5-yl H-C2H5 13.4 2-chloro-pyrid-5-yl H -CaHr (n) 13.5 2-chloro-pyrid-5-yl H c-propyl 13.6 2-chloro-pyrid-5-yl H-C4H9 (n) 13.7 2-chloro-pyrid-5-yl H -CH (CH3) 2 13.8 2-chloro-pyrid-5-yl-CH3-CH3 13.9 2-chloro-pyrid-5-yl-C2H5-CH3 13.10 2,3-dichloro-pyrid-5-yl HH 13.11 2,3-dichloro-pyrid- 5-yl H -CH3 13.12 2,3-d? Chloro-pyrid-5-yl H -C2H5 13. 13 2,3-dichloro-pyrid-5-yl -CH 3 -CH 3 13. 14 2,3-dichloro-pyrid-5-yl -C2H5 -CH3 ilo ilo 13. 21 2-chloro-thiazol-5-yl H H 13.22 2-chloro-thiazol-5-yl H-CH3 13. 23 2-chloro-thiazol-5-yl -CH3-CH3 13. 24 2-chloro-thiazol-5-yl -C2H5 -CH3 13. 25 2-Chloro-thiazol-5-yl H -C2H5 13. 26 2-chloro-thiazol-5-yl H-propyl 13. 27 2-chloro-thiazol-5-yl -CH3 c-propyl 13. 28 tetrahydrofuran-3-yl H H 13.29 tetrahydrofuran-3-yl H -CH3 13.30 tetrahydrofuran-3-yl H -C2Hs 13. 31 tetrahydrofuran-3-yl H c-propyl 13. 32 tetrahydrofuran-3-yl-CH3 -CaHs 13. 33 tetrahydrofuran-3-yl-CH3 c-propyl 13. 34 5-methyl-tetrahydrofuran-3-yl H H 13. 35 5-methyl-tetrahydrofuran-3-yl H-CH3 13. 36 5-methyl-tetrahydrofuran-3-yl H -C2H5 13. 37 5-methyl-tetrahydrofuran-3-yl H c-propyl 13. 38 5-methyl-tetrahydrofuran-3-yl -CH3-CH3

Claims (11)

. CLAIMS

1. A process for the production of a compound of the formula: wherein: Ri is hydrogen or alkyl of 1 to 4 carbon atoms; R2 is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or a radical -CH2B; A is a heterocyclic, monocyclic or bicyclic, aromatic or non-aromatic, unsubstituted radical, or - depending on the possibilities of substitution of the ring system -, one of which is mono- to penta-substituted by 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 atoms carbon, alkynyl of 2 to 3 carbon atoms, haloalkenyl of 2 to 3 carbon atoms, and has loalkynyl of 2 to 3 carbon atoms, thioalkyl of 1 to carbon atoms, halotioalkyl of 1 to 3 alkyloxy carbon atoms, propargyloxy, thioalyl, thiopropargyl, haloalyl xyl, halothioalyl, cyano, and nitro; and B is phenyl, 3-pyridyl or thiazolyl, which are optionally substituted by 1 to 3 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, haloalkylene of 2 to 3 carbon atoms, haloalkynyl of 2 to carbon atoms, haloalkoxy of 1 to 3 atoms of carbon, thioalkyl of 1 to 3 carbon atoms, halotioalkyl of 1 to carbon atoms, allyloxy, propargyloxy, thioalyl, thiopro pargyl, haloalyloxy, halothioallyl, halogen, cyano, and nitro; and optionally the possible E / Z isomers, E / Z isomer mixtures, and / or tautomers thereof, respectively free form or salt form; characterized in that a compound of the formula: wherein R1 t R2 / and A have the same meanings as the formula (I), and X is 0 or S; It is hydrolyzed with a strong acid.

2. The process according to claim 1, for the production of a compound of the formula (I) in free form.

3. The process according to one of claims 1 or 2, for the production of a compound of the formula (I), wherein it is hydrogen.

4. The process according to one of claims 1 to 3, for the production of a compound of the formula (I), wherein R2 is hydrogen, alkyl of 1 to 3 carbon atoms, or cyclopropyl.

The process according to one of claims 1 to 4, for the production of a compound of the formula (I), wherein A is 2-chloropyrid-5-yl, tetrahydrofuran-3-yl, 5-methyl- tetrahydrofuran-3-yl, or 2-chlorothiazol-5-yl.

The process according to one of claims 1 to 5, for the production of a compound of the formula (I), from a compound of the formula (II), wherein X is O.

7. The process according to one of claims 1 to 6, characterized in that a mineral acid is used.

The process according to one of claims 1 to 7, characterized in that the process is carried out in water, an alcohol, or a mixture of water with an alcohol.

9. The process according to one of claims 1 to 8, wherein the temperature is from 50 ° C to 100 ° C.

10. The process according to one of claims 1 to 9, characterized in that the process is carried out at a pH value of less than 2.

11. A compound of the formula: wherein Rx, R2, and A have the same meanings as indicated in claim 1, formula (I), and X is O or S; in free form or in salt form. RESPMSN A process for the production of a compound of the formula is described: wherein: Ri is hydrogen or alkyl of 1 to 4 carbon atoms; R2 is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 2 to 6 carbon atoms, alkynyl of 2 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or a radical -CH2B; A is a heterocyclic, monocyclic or bicyclic, aromatic or non-aromatic, unsubstituted or mono- to penta-substituted radical; and B is phenyl, 3-pyridyl or thiazolyl, which are optionally substituted by 1 to 3 substituents characterized in that a compound of the formula: («). where Rlf R2, and A have the same meanings as the formula (I), and X is O or S; It is hydrolyzed with a strong acid. The compounds of the formula (I) are suitable for the preparation of pesticides. * * * • *