CA2301172A1 - Method for the producing substituted-2-nitroguanidine derivatives - Google Patents
Method for the producing substituted-2-nitroguanidine derivatives Download PDFInfo
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- CA2301172A1 CA2301172A1 CA002301172A CA2301172A CA2301172A1 CA 2301172 A1 CA2301172 A1 CA 2301172A1 CA 002301172 A CA002301172 A CA 002301172A CA 2301172 A CA2301172 A CA 2301172A CA 2301172 A1 CA2301172 A1 CA 2301172A1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C211/00—Compounds containing amino groups bound to a carbon skeleton
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D251/00—Heterocyclic compounds containing 1,3,5-triazine rings
- C07D251/02—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings
- C07D251/08—Heterocyclic compounds containing 1,3,5-triazine rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Agricultural Chemicals And Associated Chemicals (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
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Abstract
The invention relates to a method for producing compounds of formula (I), wherein R1 is hydrogen or C1-C4 alkyl, R2 is hydrogen, C1-C6alkyl, C3-C6 cycloalkyl or a radical -CH2B, A is an unsubstituted or substituted, aromatic or non-aromatic, monocyclic or bicyclic heterocyclic radical and B is phenyl, 3-pyridyl or thiazolyl, these being substituted. The inventive method is characterised in that a compound of formula (II) wherein R1, R2 and A have the same meanings as in formula (I) and R3 is unsubstituted or substituted C11-C22 alkyl, C7-C16 cycloalkyl, C3-C20 alkenyl, C3-C20 alkinyl, N(R4)R5, optionally substituted aryl with the exception of unsubstituted and substituted phenyl, or an optionally substituted heterocyclic radical, R4 is hydrogen or C1-C12 alkyl and R5 is hydrogen, C1-C12 alkyl, C1-C12 alkyl carbonyl or C1-C12 alkoxy carbonyl is hydrolysed. The invention also relates to a method for producing compounds of formulae (II) and (III), and to a method for combating pests using compounds of formula (II). The compounds of formula (I) are suitable for producing pesticide mixtures.
Description
PI/5-30128/A ca o23oii~2 2_ooo-aoi-is~ ~rpf-, ~P~~ O~, PST - ~ ~c~~-,off Method of producing substituted 2-nitroguanidine derivatives The present invention relates to a novel type of method of producing substituted 2-nitro-guanidine derivatives.
It is known that, in order to produce 1,3-disubstituted 2-nitroguanidines, a further substituent may be introduced into monosubstituted 2-nitroguanidines (e.g. by alkylation) (see e.g. EP
patent applications 0.375.907, 0.376.279 and 0.383.091 ). Owing 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 non-selective and lead to undesired substitution products. The afore-mentioned EP
patent applications describe the production of 1,3-disubstituted 2-nitroguanidines by reacting monosubstituted nitroisothioureas with primary amines whilst cleaving mercaptan.
However, these nitroisothiourea compounds, containing alkylthio leaving groups, which are proposed as starting compounds in the known processes, can only be obtained with difficulty. In addition, in EP-A-0-483.062, a process for the production of the compounds of formula (I) by hydrolysis of hexahydro-triazines is described.
It has now been shown that the above-described methods of producing compounds of formula (I) do not satisfy the requirements demanded of a chemical production process, such as availability, toxicity, stability in storage and purity of the starting materials and excipients, reaction time, energy consumption and volumes yielded by the process, quantity and recovery of the accruing by-products and waste products, as well as purity and yield of the end product. There is therefore a need to provide improved methods of producing these compounds. It has now surprisingly been found that the method according to the invention is able to satisfy these requirements to a large extent.
Accordingly, it is the aim of the present invention to provide an improved method of producing 1-monosubstituted and 1,3-disubstituted 2-nitroguanidines from readily obtainable starting compounds, which allows specific 1,3-disubstitution without obtaining major amounts of undesired by-products.
The invention relates to a) a method of producing a compound of formula R
A\ /N N
H (I)~
R~ N, wherein R, is hydrogen or C,-C4-alkyl;
RZ is hydrogen, C,-C6-alkyl, C3-C6-cycloalkyl or a radical -CH2B;
A is an aromatic or non-aromatic, monocyclic or bicyclic heterocyclic radical which is unsubstituted or - depending on the substitution possibilities of the ring system -mono- to penta-substituted by substituents selected from the group comprising halogen, C,-C3-alkyl, C,-C3-alkoxy, halogen-C~-C3-alkyl, C,-C3-halogenalkoxy, cyclopropyl, halogencyclopropyl, C2-C3-alkenyl, C2-C3-alkynyl, C2-C3-halogenalkenyl and C2-C3-halogenalkynyl, C,-C3-alkylthio, C,-C3-halogenalkylthio, allyloxy, propargyloxy, allylthio, propargylthio, halogenallyloxy, halogenallylthio, cyano and vitro; and B is phenyl, 3-pyridyl or thiazolyl, which are optionally substituted by one to three substituents from the group comprising C~-C3-alkyl, C1-C3-halogenalkyl, cyclopropyl, halogencyclopropyl, C2-C3-alkenyl, C2-C3-alkynyl, C,-C3-alkoxy, C2-C3-halogenalkenyl, C2-C3-halogenalkynyl, C,-C3-halogenalkoxy, C~-C3-alkylthio, C,-C3-halogenalkylthio, allyloxy, propargyloxy, allylthio, propargylthio, halogenallyloxy, halogenallylthio, halogen, cyano and vitro;
and, if appropriate, the possible E/Z isomers, E/Z isomeric mixtures and/or tautomers thereof, each in free form or in salt form;
characterised in that a compound of formula /N\
A~N~N~R (II), z R~ N, wherein R,, R2 and A have the same significances as given for formula (I), and R3 is unsubstituted or substituted C"-C~-alkyl, C,-C,6-cycloalkyl, C3-C2o-alkenyl, C3-C2o-alkynyl, N(R4)R5, optionally substituted aryl except for unsubstituted and substituted phenyl; or an optionally substituted, aromatic or non-aromatic, monocyclic or bicyclic, heterocyclic radical;
R4 is hydrogen or C,-C,2-alkyl;
R5 is hydrogen, C,-C,2-alkyl, C,-C,2-alkyl-carbonyl or C,-C,2-alkoxy-carbonyl;
is hydrolysed.
The compounds of formula (I) may be present as E/Z isomers, e.g. in the following two isomeric forms H
A N A N N
~H and ~ ~ ~H
R, N, R, .N
Accordingly, any reference to compounds of formula (I) hereinafter is understood to include also their corresponding E/Z isomers, even if the latter are not specifically mentioned in each case.
The compounds of formula (I) may be present partly in the form of tautomers, for example in the forms H R2 H Rz I2 A N N A N /N A N N
~H , ~ ~ and ~ ~ ~H .
R~ N~ R~ ~N, R~ ~N~
Accordingly, any reference to compounds of formula (I) hereinbefore and hereinafter is understood to include also their corresponding tautomers, even if the latter are not specifically mentioned in each case.
The compounds of formula (1) and, where appropriate, the E/Z isomers and tautomers thereof, may be present as salts. Compounds of formula (I) having at least one basic centre may form e.g. acid addition salts. These are formed for example with strong inorganic acids, such as mineral acids, e.g. sulfuric acid, a phosphoric acid or a hydrohalic acid, with strong organic carboxylic acids, typically C,-C4alkanecarboxylic acids substituted where appropriate for example by halogen, e.g. acetic acid, such as optionally unsaturated dicarboxylic acids, e.g. oxalic, malonic, malefic, fumaric or phthalic acid, such as hydroxycarboxylic acids, e.g. ascorbic, lactic, malic, tartaric or citric acid, or benzoic acid, or with organic sulfonic acids, such as C,-C4alkanesulfonic or arylsulfonic acids substituted where appropriate for example by halogen, e.g. methanesulfonic or p-toluenesulfonic acid.
Salts of compounds of formula (I) with acids of the said kind are preferably obtained when working up the reaction mixtures.
In a broader sense, compounds of formula (I) with at least one acid group can form salts with bases. Suitable salts with bases are for example metal salts, typically alkali or alkaline earth metal salts, e.g. 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, e.g. ethyl, diethyl, methyl or dimethylpropylamine, or a mono-, di-or trihydroxy-lower alkylamine, e.g. mono-, di- or triethanolamine. Corresponding internal salts where appropriate may also be formed. Preferred compounds within the scope of this invention are agrochemically advantageous salts. Hereinbefore and hereinafter, the free compounds of formula (I) are understood where appropriate to include also by analogy the corresponding salts, and the salts are understood to include also the free compounds of formula (I). The same applies to E/Z isomers and tautomers of compounds of formula (I) and salts thereof. The free form is preferred.
In the definition of formulae (I) to (VI) given above and below, the individual generic terms are to be understood as follows:
The halogen atoms considered as substituents may be both fluorine and chlorine, and bromine and iodine, whereby fluorine, chlorine and bromine are preferred, especially chlorine. Halogen in this context is understood to be an independent substituent or part of a substituent, such as in halogenalkyl, halogenalkylthio, halogenalkoxy, halogencycloalkyl, halogenalkenyl, halogenalkynyl, halogenallyloxy or halogenallylthio. The alkyl, alkylthio, alkenyl, alkynyl and alkoxy radicals considered as substituents may be straight-chained or branched. If not defined otherwise, alkyl groups have up to 6 carbon atoms.
Examples of such alkyls which may be mentioned are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.-butyl or tert.-butyl. Suitable alkoxy radicals which may be mentioned are, inter alias methoxy, ethoxy, propoxy, isopropoxy or butoxy and the isomers thereof.
Alkylthio is for example methylthio, ethylthio, isopropylthio, propylthio or the isomeric butylthio. If the alkyl, alkoxy, alkenyl, alkynyl or cycloalkyl groups considered as substituents are substituted by halogen, they may be only partially halogenated or also 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 trisubstituted by fluorine, chlorine and/or bromine, such as CHF2 or CF3; ethyl which is mono- to pentasubstituted by fluorine, chlorine and/or bromine, such as CH2CF3, CF2CF3, CF2CC13, CF2CHC12, CF2CHF2, CFZCFCI2, CF2CHBr2, CF2CHCIF, CF2CHBrF or CCIFCHCIF; propyl or isopropyl, mono-to heptasubstituted by fluorine, chlorine and/or bromine, such as CH2CHBrCH2Br, CF2CHFCF3, CHzCF2CF3 or CH(CF3)2; butyl or one of its isomers, mono- to nonasubstituted by fluorine, chlorine and/or bromine, such as 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.
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 allyloxy, propargyloxy, allylthio or propargylthio are separated from the connection point to the hetero atom (N, O or S) preferably by a saturated carbon atom.
If the defined alkyl, alkoxy, alkenyl, alkynyl or cycloalkyl groups are substituted by other substituents, they may be mono- or repeatedly substituted by identical or different substituents from those listed. In the substituted groups, it is preferable for one or two further substituents to be present. The cycloalkyl radicals considered as substituents may be, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. The cycloalkyl radicals considered as substituents R3 may be, for example, cyclodecyl, cyclohexadecyl, cyclododecyl or cyclooctadecyl.
Aryl signifies phenyl, naphthyl, phenanthrenyl or anthracenyl, in conjunction with the substituents R3 in the compounds of formulae (II) and (III) in particular naphthyl, and in conjunction with the remaining substituents listed in particular phenyl.
In the context of the present invention, a heterocyclic radical preferably signifies a 5- to 7-membered, aromatic or non-aromatic ring with one to three hetero atoms selected from the group comprising N, O and S. Preference is given to aromatic 5- and 6-rings, which have a nitrogen atom as the hetero atom and optionally one further hetero atom, preferably nitrogen, oxygen or sulphur, especially nitrogen.
It has now surprisingly been found that the process according to the invention is able to satisfy these requirements.
The hydrolysis process according to the invention may be carried out both in an acidic, especially a strongly acidic medium, and in a basic medium. In the acidic range, pH values of 5 to 1, especially 3 to 1, are preferred. In the basic range, a pH value greater than 7 and up to 12, especially 8 to 12, in particular 8 to 10, is preferred. The reaction is carried out at normal pressure and at a temperature of 0 to 120°C, preferably 20 to 80°C.
The reaction is carried out in a solvent or diluent that is inert towards the reaction components. Suitable solvents are, in particular, alcohols such as methanol, ethanol, propanol and isopropanol, as well as especially water. Further appropriate solvents are e.g.
ethers, such as tetrahydrofuran and dioxane, as well as other solvents which do not adversely affect the reaction. The solvents may also be used as mixtures. A
compound of formula (II) is preferably hydrolysed in an aqueous medium or in a mixture of water with an alcohol.
Suitable acids for carrying out the process are preferably mineral acids, e.g.
sulfuric acid, a phosphoric acid or a hydrohalic acid, an organic carboxylic acid, typically C,-C4alkane-carboxylic acids substituted where appropriate for example by halogen, e.g.
acetic acid, such as optionally unsaturated dicarboxylic acids , e.g. oxalic, malonic, malefic, fumaric or phthalic acid, typically hydroxycarboxylic acids, e.g. ascorbic, lactic, malic, tartaric or citric acid, or benzoic acid, or an organic sulfonic acid, typically C,-C4alkane- or arylsulfonic acids substituted where appropriate for example by halogen, e.g. methanesulfonic or p-toluene-sulfonic 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 Na2C03, NaHC03, K2C03; phosphates such as Na3P04, Na2HP04, alcoholates such as sodium methanolate, sodium ethanolate and K-tert.-butanolate, organic amines such as morpholine, piperidine, pyrrolidine, a mono-, di- or tri-lower alkylamine, e.g. ethyl-, diethyl, triethyl- or dimethyl-propyl-amine, or a mono-, di- or trihydroxy lower alkylamine, e.g. mono-, di-or triethanol-amine, or dialkylaniline, for example N,N-dimethyl- or N,N-diethylaniline, as well as salts of organic acids, such as sodium acetate, potassium acetate or sodium benzoate, or mixtures thereof, for example acetate or phosphate buffers.
The process according to the invention is preferably used to produce compounds of formula (I) in which the heterocyclic radical A is unsaturated and is bonded by a carbon atom as a ring member to the fundamental substance. Especially preferred radicals A are pyridyl, thiazolyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, N-oxido-pyridinio, oxazolyl, isoxazolyl, thienyl, morpholinyl, piperidinyl, pyridinyl and pyrazinyl; most particularly pyridyl, thiazolyl, tetrahydrofuranyl and N-oxido-pyridinio, especially 3-pyridyl, 2-halogenpyrid-5-yl, 2,3-dihalogenpyrid-5-yl, 2-halogenthiazol-5-yl, tetrahydrofuran-3-yl, 5-methyl-tetrahydrofuran-3-yl, 1-oxopyrid-3-yl, 1-oxo-2-halogenpyrid-5-yl and 1-oxo-2,3-dihalogenpyrid-5-yl.
Equally preferably, the heterocycles A carry one to three substituents from the group halogen, C,-C3-alkyl, C,-C3-halogenalkyl and C,-C3-halogenalkoxy each with 1 to 7 halogen atoms, and C,-C3-alkoxy.
Furthermore, compounds of formula (I) are preferably produced according to the invention, in which the radical B is a phenyl, pyridyl or thiazolyl radical that is unsubstituted or may be substituted by one to two radicals from the group halogen, C,-C3-alkyl, C,-C3-halogenalkyl and C~-C3-halogenalkoxy each with 1 to 7 halogen atoms, and C,-C3-alkoxy.
Of the compounds of formula (I) to be produced according to the invention, those that are notable are those in which R, is hydrogen, R2 is hydrogen, methyl, ethyl or cyclopropyl and A is pyridyl, 1-oxopyridyl, tetrahydrofuranyl, thiazolyl, or A is pyridyl, 1-oxopyridinio, tetra-hydrofuranyl or thiazolyl which is respectively substituted by one to three substituents from the group halogen, C,-C3-alkyl, C,-C3-halogenalkyl and C,-C3-halogenalkoxy each with 1 to 7 halogen atoms, and C,-C3-alkoxy. In this context, the preparation of those compounds of formula (I) is of particular interest, in which a) R~ is hydrogen;
b) R2 is hydrogen, C,-C3-alkyl or cyclopropyl, especially methyl;
c) A is 2-chloropyrid-5-yl, tetrahydrofuran-3-yl, 2-methyl-tetrahydrofuran-4-yl or 2-chloro-thiazol-5-yl.
In the compounds of formulae (II) and (III) listed hereinbefore and hereinafter, the substituents for the radical R3 which may be considered are in particular C"-C,6-alkyl;
C,~-C,8-alkyl substituted by hydroxy or -COO-C,-C,6-alkyl; C3-C,$-alkenyl optionally substituted by phenyl or hydroxy; C3-C,8-alkynyl optionally substituted by phenyl; cyclooctyl, cyclodecyl, cycloheptyl, cyclododecyl, thiazolyl, pyridyl, pyridinyl, pyrazinyl or optionally substituted naphthyl.
A further object of the invention is b) a method of producing a compound of formula (II), and optionally the E/Z
isomers, E/Z
isomeric mixtures and/or tautomers thereof, each in free form or in salt form, characterised in that a compound of formula _g_ ~N~
HEN NI ~R (III).
z N
~N02 wherein R2 and R3 are as defined above for formula (II), and optionally the E/Z isomers, E/Z
isomeric mixtures and/or tautomers thereof, each in free form or in salt form, is reacted with a compound of formula Y A
(IV), R~
which is known or may be produced analogously to methods known per se, wherein R, and A are defined as given above for formula (I) and Y is a leaving group, preferably halogen, preferably in the presence of a base.
A further object of the invention is c) a method of producing the compounds of formula (III), and optionally the E/Z isomers, E/Z isomeric mixtures and/or tautomers thereof, each in free form or in salt form, characterised in that a compound of formula H
R/N NH2 (V)' z N
02N ~
which is known or may be produced analogously to methods known per se, and wherein R2 has the same significance as defined for formula (I), is reacted with a compound of formula H2N-R3 (VI), wherein R3 has the same significance as defined above for the compounds of formula (II), and which is known or may be produced analogously to methods known per se, in the presence of an excess of formaldehyde or paraformaldehyde.
A further object of the invention is d) a method of producing a compound of formula (I), and optionally the E/Z
isomers, E/Z
isomeric mixtures and/or tautomers thereof, each in free form or in salt form, characterised _g_ in that a compound of formula (V) is converted into a compound of formula (III) by reacting it with a compound of formula (VI) and formaldehyde or paraformaldehyde; this compound of formula (III) is converted into a compound of formula (II) by a compound of formula (IV), and this compound of formula (II) is hydrolysed.
A further object of the invention is e) the use of the compounds of formula (II) in the preparation of the compounds of formula (I).
Preferred embodiments of the method according to variants b) to d) may be taken from the examples.
The starting compounds or starting products of formulae (II) and (III) considered for the method according to the invention, and optionally the possible E/Z isomers, E/Z isomeric mixtures and/or tautomers thereof, each in free form or in salt form, are new.
They similarly form an object of the invention.
The compounds of formula (I) which are produced according to the invention are valuable active ingredients in pest control, that are well tolerated by warm-blooded animals, fish and plants. The compounds of formula (I) are especially suitable for the control of insects and arachnids, which appear on crops and ornamentals in agriculture, especially in cotton, vegetable and fruit plantations, in forestry, in the protection of stock and material, as well as in the hygiene sector, especially on domestic animals and productive livestock. The compounds are especially effective against plant-damaging sucking insects, especially against aphids and plant and leaf hoppers. Pesticidally active substituted 2-nitroguanidines of the type that may be produced according to the invention are described e.g.
in EP patent applications 376.279, 375.907 and 383.091.
Preparation examples Example P1.1: Preparation of the compound of formula H
N-O N~N~ -/N-n-C~8H3~
z N
i A mixture of 2.4 g of 1-methyl-2-nitroguanidine, 5.5 g of octadecylamine, 20 ml of ethanol and 3.2 ml of a 37% solution of formaldehyde in water is heated to 50°C
and stirred at this temperature for 4 hours. The mixture is then evaporated to dryness under vacuum, the residue stirred with diethyl ether and the title compound isolated by filtration (compound 1.10).
Example P1.2: Preparation of the compound of formula H
N~ ~CH2 N~ N
02N, N~
i A mixture of 3.54 g of 1-methyl-2-nitroguanidine, 2.7 ml of allylamine, 50 ml of toluene and 2.7 g of paraformaldehyde is mixed with 3 drops of concentrated hydrochloric acid and heated for 20 hours on a water separator. Then, the mixture is evaporated to dryness under vacuum, the residue taken up with dichloromethane/methanol (98:2), filtered over silica gel and the filtrate concentrated by evaporation. The title compound is obtained by recrystallisation from isopropanol with a melting point of 53-55 °C
(compound 1.14).
Example P1.3: Preparation of the compound of formula H
N
N- N
02N N ~ -N
i A mixture of 5.9 g of 1-methyl-2-nitroguanidine, 5.2 g of 3-aminopyridine, 4.5 g of para-formaldehyde, 60 ml of dioxane and 0.24 g of p-toluenesulfonic acid is heated for 20 hours on a water separator. After cooling, the reaction mixture is filtered and the residue of filtration is washed with dimethylformamide and toluene. This yields the title compound with a melting point of 204-208°C (compound 1.26).
The following compounds of formula (III) listed in Table 1 can also be obtained analogously to the above methods of examples P1.1 to P1.3.
Table 1: Compounds of formula ~N~
,N N~ (Illa) H ~ CH3 N
~
No. R3 phys. data 1.1 cyclooctyl 1.2 cyclodecyl 1.3 cycloheptyl 1.4 -(CH2),o-CH3 1.5 -(CH2)"-CH3 m.p. 85-87 C
1.6 -(CH2),2-CH3 1.7 -(CH2),3-CH3 1.8 -(CH2),4-CH3 1.9 -(CH2), 5-CH3 1.10 -(CH2),~-CH3 1.11 -(CH2)8-CH=CH-(CH2),-CH3 (cis) 1.12 -(CHZ),o-COOH
1.13 -(CHZ)"-COOH m.p. 93-95 C
PI/5-30128/A ca o23om2 Zooo-o2-is No. R3 phys. data 1.14 -CH2-CH=CH2 m.p. 53-55 °C
1.15 -CH-(CH20H)CH(OH)-CH=CH-(CH2)~z-CH3 1.16 -CH2-CH=CH(CH3)-(CHz)2-CH=C(CH3)2 1.17 -CH-(CH20H)CH(OH)-C---C-(CH2),2-CH3 1.18 -(CH2)s-C=C-CsHs 1.19 -CHZ-C---C-C6H5 1.20 \ \ \
1.21 1.22 / / /
\ \ \
1.23 naphth-1-yl 1.24 naphth-2-yl 1.25 thiazol-2-yl 1.26 pyrid-3-yl m.p. 204-208 °C
1.27 pyrid-4-yl 1.28 3-bromonaphth-2-yl PI/5-30128/A ca o23om2 Zooo-o2-is No. R3 phys. data 1.29 1-hydroxy-naphth-2-yl 1.30 4-methoxy-naphth-2-yl 1.31 5-hydroxy-naphth-2-yl 1.32 1-chloronaphth-2-yl 1.33 8-nitronapht-2-yl 1.34 -NHCOOC2H5 m.p. 203-204 °C
1.35 m.p. 156-158 °C
O
O
1.36 O
~NH
1.37 cyclododecyl m.p. 137-139 °C
1.38 O m.p. 56-57 °C
I ~ ~~~~H2~"
CI
1.39 -CH2)"-C(=O)OCH3 m.p. 91-94 °C
Example P2.1: Preparation of the compound of formula N
~N~ ~N n-ClsHs~
N
CI
PI/5-30128/A ca o23om2 Zooo-o2-is A mixture of 6.0 g of the compound obtainable according to example P1.1, 2.8 g of 2-chloro-5-chloromethylpyridine and 4.8 g of potassium carbonate in 20 ml of dimethylformamide is stirred for 10 hours at 50 °C. Then, the reaction mixture is filtered, the filtrate concentrated by evaporation under vacuum, and the recrystallised from ethanol. This yields the title compound with a melting point of 95-97°C (compound 10.8.1 ).
The following compounds of formula (II) listed in Tables 2 to 13 can also be obtained analogously to the above method of example P2.1.
Table A Compounds of formula /N\
A~N~N~ (Ila), H N
A.1 cyclooctyl CH=C(CH3)2 A.2 cyclodecyl A.17 -CH-(CH20H)CH(OH)-C---C-A.3 cycloheptyl (CH2),2-CH3 A.4 -(CH2),o-CH3 A.18 -(CH2)s-C=C-CsHs A.5 -(CH2)"-CH3 A.19 -CH2-C---C-C6H5 A.6 -(CHz),2-CH3 A.20 / / /
A.7 -(CH2)~3-CH3 A.8 -(CH2pa-CH3 \ \ \
A.9 -(CH2), 5-CH3 A.10 -(CH2)»-CH3 A.21 A.11 -(CH2)a-CH=CH-(CHZ)~-CH3 (cis) A.12 -(CH2),o-COOH
A.13 -(CH2)"-COOH
A.14 -CH2-CH=CH2 A.22 A.15 -CH-(CHZOH)CH(OH)-CH=CH-(CH2),z-CH3 \ \ \
A.16 -CH2-CH=CH(CH3)-(CH2)2- A.23 naphth-1-yl PI/5-30128/A ca o23om2 Zooo-o2-is No. R -. No. Rs A.24 naphth-2-yl A.35 A.25 thiazol-2-yl O
A.26 pyrid-3-yl O
A.27 pyrid-4-yl A.36 O
A.28 3-bromonaphth-2-yl A.29 1-hydroxy-naphth-2-yl ~NH
A.30 4-methoxy-naphth-2-yl A.31 5-hydroxy-naphth-2-yl A.37 cyclododecyl A.32 1-chloronaphth-2-yl A.38 O
A.33 8-nitro-naphth-2-yl i \ 0..
-/ (CH2)~W
4.34 -NHCOOC2H5 CI S
A.39 -CH2)1~-C(=O)OCH3 S
Table 2: Compounds of the general formula (Ila), wherein A signifies ~I~~ and !/N
R3 corresponds in each case to one line of Table A.
Compound 2.A.5: m.p. 119-121 C
Compound 2.A.37: m.p. 137-139 C
Compound 2.A.38: m.p. 76-78 C
Compound 2.A.39: m.p. 90-92 C
S
Table 3: Compounds of the general formula (Ila), wherein A signifies < ~ and N
corresponds in each case to one line of Table A.
Br Table 4: Compounds of the general formula (Ila), wherein A signifies ~ ~ and N
R3 corresponds in each case to one line of Table A.
HsC S
Table 5: Compounds of the general formula (Ila), wherein A signifies N
and R3 corresponds in each case to one line of Table A.
Table 6: Compounds of the general formula (Ila), wherein A signifies O
and R3 corresponds in each case to one line of Table A.
Table 7: Compounds of the general formula (Ila), wherein A signifies ~ and R3 O
corresponds in each case to one line of Table A.
CI
Table 8: Compounds of the general formula (Ila), wherein A signifies ~ ~ and N-O
R3 corresponds in each case to one line of Table A.
Table 9: Compounds of the general formula (Ila), wherein A signifies CI ~ / and R3 corresponds in each case to one line of Table A.
N
Compound 9.A.10: m.p. 95-97C.
Compound 9.A.14: m.p. 75-77C.
Compound 9.A.26: m.p. 222C.
Compound 9.A.34: m.p. 200C.
Compound 9.A.35: m.p. 178-180 C.
Compound 9.A.36: m.p. 214 C.
Table 10: Compounds of the general formula (Ila), wherein A signifies ~ and N
R3 corresponds in each case to one line of Table A.
PI/5-30128/A ca o23om2 Zooo-o2-is Table 11: Compounds of the general formula (Ila), wherein A signifies N and I+
O
R3 corresponds in each case to one line of Table A.
Table 12: Compounds of the general formula (Ila), wherein A signifies CI \N
I+
O
and R3 corresponds in each case to one line of Table A.
CI
Table 13: Compounds of the general formula (Ila), wherein A signifies CI N
and R3 corresponds in each case to one line of Table A.
Example 3.1: Preparation of the compound of formula H H ~ CI
I I
H C~N~N / N
'I3 N
~ N02 4.0 g of the compound obtainable according to example P2.1 are stirred for 16 hours at 50°
C in 20 ml of methanol and 25 ml of 1 n hydrochloric acid. The reaction mixture is filtered and the residue of filtration washed with methanol and dried. This yields the title product with a melting point of 147-149°C (compound 14.6).
The following compounds of formula (I) listed in Table 14 can also be obtained analogously to the above method of example P3.1.
PI/5-30128/A ca o23om2 Zooo-o2-is Table 14: Compounds of the general formula N-H CI) N
N
H A
No. A Phys.data 14.1 G
N
14.2 H3C
N
14.3 /
N
14.4 Br N
14.5 O
m.p. 147-149°C
14.6 CI
N
14.7 /
CI N.~.
I_ O
14.8 CI /
~J
CI N
14.9 N
PI/5-30128/A ca o23om2 Zooo-o2-is No. A Phys.data 14.10 H3C
O
14.11 CI
N-O
14.12 /
N
I+
O
A further object of the invention is f) a method of controlling pests, especially animal pests, particularly insects and members of the order Acarina, using the compounds of formula (II). The said animal pests include, for example, those that are mentioned in the European Patent application EP-A-736'252. The pests mentioned therein are thus included by reference in the object of the present invention. The method of controlling the said pests and the composition and preparation of the corresponding pesticides are described in EP-A-736'252 and are included by reference in the object of the present invention.
It is known that, in order to produce 1,3-disubstituted 2-nitroguanidines, a further substituent may be introduced into monosubstituted 2-nitroguanidines (e.g. by alkylation) (see e.g. EP
patent applications 0.375.907, 0.376.279 and 0.383.091 ). Owing 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 non-selective and lead to undesired substitution products. The afore-mentioned EP
patent applications describe the production of 1,3-disubstituted 2-nitroguanidines by reacting monosubstituted nitroisothioureas with primary amines whilst cleaving mercaptan.
However, these nitroisothiourea compounds, containing alkylthio leaving groups, which are proposed as starting compounds in the known processes, can only be obtained with difficulty. In addition, in EP-A-0-483.062, a process for the production of the compounds of formula (I) by hydrolysis of hexahydro-triazines is described.
It has now been shown that the above-described methods of producing compounds of formula (I) do not satisfy the requirements demanded of a chemical production process, such as availability, toxicity, stability in storage and purity of the starting materials and excipients, reaction time, energy consumption and volumes yielded by the process, quantity and recovery of the accruing by-products and waste products, as well as purity and yield of the end product. There is therefore a need to provide improved methods of producing these compounds. It has now surprisingly been found that the method according to the invention is able to satisfy these requirements to a large extent.
Accordingly, it is the aim of the present invention to provide an improved method of producing 1-monosubstituted and 1,3-disubstituted 2-nitroguanidines from readily obtainable starting compounds, which allows specific 1,3-disubstitution without obtaining major amounts of undesired by-products.
The invention relates to a) a method of producing a compound of formula R
A\ /N N
H (I)~
R~ N, wherein R, is hydrogen or C,-C4-alkyl;
RZ is hydrogen, C,-C6-alkyl, C3-C6-cycloalkyl or a radical -CH2B;
A is an aromatic or non-aromatic, monocyclic or bicyclic heterocyclic radical which is unsubstituted or - depending on the substitution possibilities of the ring system -mono- to penta-substituted by substituents selected from the group comprising halogen, C,-C3-alkyl, C,-C3-alkoxy, halogen-C~-C3-alkyl, C,-C3-halogenalkoxy, cyclopropyl, halogencyclopropyl, C2-C3-alkenyl, C2-C3-alkynyl, C2-C3-halogenalkenyl and C2-C3-halogenalkynyl, C,-C3-alkylthio, C,-C3-halogenalkylthio, allyloxy, propargyloxy, allylthio, propargylthio, halogenallyloxy, halogenallylthio, cyano and vitro; and B is phenyl, 3-pyridyl or thiazolyl, which are optionally substituted by one to three substituents from the group comprising C~-C3-alkyl, C1-C3-halogenalkyl, cyclopropyl, halogencyclopropyl, C2-C3-alkenyl, C2-C3-alkynyl, C,-C3-alkoxy, C2-C3-halogenalkenyl, C2-C3-halogenalkynyl, C,-C3-halogenalkoxy, C~-C3-alkylthio, C,-C3-halogenalkylthio, allyloxy, propargyloxy, allylthio, propargylthio, halogenallyloxy, halogenallylthio, halogen, cyano and vitro;
and, if appropriate, the possible E/Z isomers, E/Z isomeric mixtures and/or tautomers thereof, each in free form or in salt form;
characterised in that a compound of formula /N\
A~N~N~R (II), z R~ N, wherein R,, R2 and A have the same significances as given for formula (I), and R3 is unsubstituted or substituted C"-C~-alkyl, C,-C,6-cycloalkyl, C3-C2o-alkenyl, C3-C2o-alkynyl, N(R4)R5, optionally substituted aryl except for unsubstituted and substituted phenyl; or an optionally substituted, aromatic or non-aromatic, monocyclic or bicyclic, heterocyclic radical;
R4 is hydrogen or C,-C,2-alkyl;
R5 is hydrogen, C,-C,2-alkyl, C,-C,2-alkyl-carbonyl or C,-C,2-alkoxy-carbonyl;
is hydrolysed.
The compounds of formula (I) may be present as E/Z isomers, e.g. in the following two isomeric forms H
A N A N N
~H and ~ ~ ~H
R, N, R, .N
Accordingly, any reference to compounds of formula (I) hereinafter is understood to include also their corresponding E/Z isomers, even if the latter are not specifically mentioned in each case.
The compounds of formula (I) may be present partly in the form of tautomers, for example in the forms H R2 H Rz I2 A N N A N /N A N N
~H , ~ ~ and ~ ~ ~H .
R~ N~ R~ ~N, R~ ~N~
Accordingly, any reference to compounds of formula (I) hereinbefore and hereinafter is understood to include also their corresponding tautomers, even if the latter are not specifically mentioned in each case.
The compounds of formula (1) and, where appropriate, the E/Z isomers and tautomers thereof, may be present as salts. Compounds of formula (I) having at least one basic centre may form e.g. acid addition salts. These are formed for example with strong inorganic acids, such as mineral acids, e.g. sulfuric acid, a phosphoric acid or a hydrohalic acid, with strong organic carboxylic acids, typically C,-C4alkanecarboxylic acids substituted where appropriate for example by halogen, e.g. acetic acid, such as optionally unsaturated dicarboxylic acids, e.g. oxalic, malonic, malefic, fumaric or phthalic acid, such as hydroxycarboxylic acids, e.g. ascorbic, lactic, malic, tartaric or citric acid, or benzoic acid, or with organic sulfonic acids, such as C,-C4alkanesulfonic or arylsulfonic acids substituted where appropriate for example by halogen, e.g. methanesulfonic or p-toluenesulfonic acid.
Salts of compounds of formula (I) with acids of the said kind are preferably obtained when working up the reaction mixtures.
In a broader sense, compounds of formula (I) with at least one acid group can form salts with bases. Suitable salts with bases are for example metal salts, typically alkali or alkaline earth metal salts, e.g. 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, e.g. ethyl, diethyl, methyl or dimethylpropylamine, or a mono-, di-or trihydroxy-lower alkylamine, e.g. mono-, di- or triethanolamine. Corresponding internal salts where appropriate may also be formed. Preferred compounds within the scope of this invention are agrochemically advantageous salts. Hereinbefore and hereinafter, the free compounds of formula (I) are understood where appropriate to include also by analogy the corresponding salts, and the salts are understood to include also the free compounds of formula (I). The same applies to E/Z isomers and tautomers of compounds of formula (I) and salts thereof. The free form is preferred.
In the definition of formulae (I) to (VI) given above and below, the individual generic terms are to be understood as follows:
The halogen atoms considered as substituents may be both fluorine and chlorine, and bromine and iodine, whereby fluorine, chlorine and bromine are preferred, especially chlorine. Halogen in this context is understood to be an independent substituent or part of a substituent, such as in halogenalkyl, halogenalkylthio, halogenalkoxy, halogencycloalkyl, halogenalkenyl, halogenalkynyl, halogenallyloxy or halogenallylthio. The alkyl, alkylthio, alkenyl, alkynyl and alkoxy radicals considered as substituents may be straight-chained or branched. If not defined otherwise, alkyl groups have up to 6 carbon atoms.
Examples of such alkyls which may be mentioned are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec.-butyl or tert.-butyl. Suitable alkoxy radicals which may be mentioned are, inter alias methoxy, ethoxy, propoxy, isopropoxy or butoxy and the isomers thereof.
Alkylthio is for example methylthio, ethylthio, isopropylthio, propylthio or the isomeric butylthio. If the alkyl, alkoxy, alkenyl, alkynyl or cycloalkyl groups considered as substituents are substituted by halogen, they may be only partially halogenated or also 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 trisubstituted by fluorine, chlorine and/or bromine, such as CHF2 or CF3; ethyl which is mono- to pentasubstituted by fluorine, chlorine and/or bromine, such as CH2CF3, CF2CF3, CF2CC13, CF2CHC12, CF2CHF2, CFZCFCI2, CF2CHBr2, CF2CHCIF, CF2CHBrF or CCIFCHCIF; propyl or isopropyl, mono-to heptasubstituted by fluorine, chlorine and/or bromine, such as CH2CHBrCH2Br, CF2CHFCF3, CHzCF2CF3 or CH(CF3)2; butyl or one of its isomers, mono- to nonasubstituted by fluorine, chlorine and/or bromine, such as 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.
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 allyloxy, propargyloxy, allylthio or propargylthio are separated from the connection point to the hetero atom (N, O or S) preferably by a saturated carbon atom.
If the defined alkyl, alkoxy, alkenyl, alkynyl or cycloalkyl groups are substituted by other substituents, they may be mono- or repeatedly substituted by identical or different substituents from those listed. In the substituted groups, it is preferable for one or two further substituents to be present. The cycloalkyl radicals considered as substituents may be, for example, cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl. The cycloalkyl radicals considered as substituents R3 may be, for example, cyclodecyl, cyclohexadecyl, cyclododecyl or cyclooctadecyl.
Aryl signifies phenyl, naphthyl, phenanthrenyl or anthracenyl, in conjunction with the substituents R3 in the compounds of formulae (II) and (III) in particular naphthyl, and in conjunction with the remaining substituents listed in particular phenyl.
In the context of the present invention, a heterocyclic radical preferably signifies a 5- to 7-membered, aromatic or non-aromatic ring with one to three hetero atoms selected from the group comprising N, O and S. Preference is given to aromatic 5- and 6-rings, which have a nitrogen atom as the hetero atom and optionally one further hetero atom, preferably nitrogen, oxygen or sulphur, especially nitrogen.
It has now surprisingly been found that the process according to the invention is able to satisfy these requirements.
The hydrolysis process according to the invention may be carried out both in an acidic, especially a strongly acidic medium, and in a basic medium. In the acidic range, pH values of 5 to 1, especially 3 to 1, are preferred. In the basic range, a pH value greater than 7 and up to 12, especially 8 to 12, in particular 8 to 10, is preferred. The reaction is carried out at normal pressure and at a temperature of 0 to 120°C, preferably 20 to 80°C.
The reaction is carried out in a solvent or diluent that is inert towards the reaction components. Suitable solvents are, in particular, alcohols such as methanol, ethanol, propanol and isopropanol, as well as especially water. Further appropriate solvents are e.g.
ethers, such as tetrahydrofuran and dioxane, as well as other solvents which do not adversely affect the reaction. The solvents may also be used as mixtures. A
compound of formula (II) is preferably hydrolysed in an aqueous medium or in a mixture of water with an alcohol.
Suitable acids for carrying out the process are preferably mineral acids, e.g.
sulfuric acid, a phosphoric acid or a hydrohalic acid, an organic carboxylic acid, typically C,-C4alkane-carboxylic acids substituted where appropriate for example by halogen, e.g.
acetic acid, such as optionally unsaturated dicarboxylic acids , e.g. oxalic, malonic, malefic, fumaric or phthalic acid, typically hydroxycarboxylic acids, e.g. ascorbic, lactic, malic, tartaric or citric acid, or benzoic acid, or an organic sulfonic acid, typically C,-C4alkane- or arylsulfonic acids substituted where appropriate for example by halogen, e.g. methanesulfonic or p-toluene-sulfonic 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 Na2C03, NaHC03, K2C03; phosphates such as Na3P04, Na2HP04, alcoholates such as sodium methanolate, sodium ethanolate and K-tert.-butanolate, organic amines such as morpholine, piperidine, pyrrolidine, a mono-, di- or tri-lower alkylamine, e.g. ethyl-, diethyl, triethyl- or dimethyl-propyl-amine, or a mono-, di- or trihydroxy lower alkylamine, e.g. mono-, di-or triethanol-amine, or dialkylaniline, for example N,N-dimethyl- or N,N-diethylaniline, as well as salts of organic acids, such as sodium acetate, potassium acetate or sodium benzoate, or mixtures thereof, for example acetate or phosphate buffers.
The process according to the invention is preferably used to produce compounds of formula (I) in which the heterocyclic radical A is unsaturated and is bonded by a carbon atom as a ring member to the fundamental substance. Especially preferred radicals A are pyridyl, thiazolyl, tetrahydrofuranyl, dihydrofuranyl, furanyl, N-oxido-pyridinio, oxazolyl, isoxazolyl, thienyl, morpholinyl, piperidinyl, pyridinyl and pyrazinyl; most particularly pyridyl, thiazolyl, tetrahydrofuranyl and N-oxido-pyridinio, especially 3-pyridyl, 2-halogenpyrid-5-yl, 2,3-dihalogenpyrid-5-yl, 2-halogenthiazol-5-yl, tetrahydrofuran-3-yl, 5-methyl-tetrahydrofuran-3-yl, 1-oxopyrid-3-yl, 1-oxo-2-halogenpyrid-5-yl and 1-oxo-2,3-dihalogenpyrid-5-yl.
Equally preferably, the heterocycles A carry one to three substituents from the group halogen, C,-C3-alkyl, C,-C3-halogenalkyl and C,-C3-halogenalkoxy each with 1 to 7 halogen atoms, and C,-C3-alkoxy.
Furthermore, compounds of formula (I) are preferably produced according to the invention, in which the radical B is a phenyl, pyridyl or thiazolyl radical that is unsubstituted or may be substituted by one to two radicals from the group halogen, C,-C3-alkyl, C,-C3-halogenalkyl and C~-C3-halogenalkoxy each with 1 to 7 halogen atoms, and C,-C3-alkoxy.
Of the compounds of formula (I) to be produced according to the invention, those that are notable are those in which R, is hydrogen, R2 is hydrogen, methyl, ethyl or cyclopropyl and A is pyridyl, 1-oxopyridyl, tetrahydrofuranyl, thiazolyl, or A is pyridyl, 1-oxopyridinio, tetra-hydrofuranyl or thiazolyl which is respectively substituted by one to three substituents from the group halogen, C,-C3-alkyl, C,-C3-halogenalkyl and C,-C3-halogenalkoxy each with 1 to 7 halogen atoms, and C,-C3-alkoxy. In this context, the preparation of those compounds of formula (I) is of particular interest, in which a) R~ is hydrogen;
b) R2 is hydrogen, C,-C3-alkyl or cyclopropyl, especially methyl;
c) A is 2-chloropyrid-5-yl, tetrahydrofuran-3-yl, 2-methyl-tetrahydrofuran-4-yl or 2-chloro-thiazol-5-yl.
In the compounds of formulae (II) and (III) listed hereinbefore and hereinafter, the substituents for the radical R3 which may be considered are in particular C"-C,6-alkyl;
C,~-C,8-alkyl substituted by hydroxy or -COO-C,-C,6-alkyl; C3-C,$-alkenyl optionally substituted by phenyl or hydroxy; C3-C,8-alkynyl optionally substituted by phenyl; cyclooctyl, cyclodecyl, cycloheptyl, cyclododecyl, thiazolyl, pyridyl, pyridinyl, pyrazinyl or optionally substituted naphthyl.
A further object of the invention is b) a method of producing a compound of formula (II), and optionally the E/Z
isomers, E/Z
isomeric mixtures and/or tautomers thereof, each in free form or in salt form, characterised in that a compound of formula _g_ ~N~
HEN NI ~R (III).
z N
~N02 wherein R2 and R3 are as defined above for formula (II), and optionally the E/Z isomers, E/Z
isomeric mixtures and/or tautomers thereof, each in free form or in salt form, is reacted with a compound of formula Y A
(IV), R~
which is known or may be produced analogously to methods known per se, wherein R, and A are defined as given above for formula (I) and Y is a leaving group, preferably halogen, preferably in the presence of a base.
A further object of the invention is c) a method of producing the compounds of formula (III), and optionally the E/Z isomers, E/Z isomeric mixtures and/or tautomers thereof, each in free form or in salt form, characterised in that a compound of formula H
R/N NH2 (V)' z N
02N ~
which is known or may be produced analogously to methods known per se, and wherein R2 has the same significance as defined for formula (I), is reacted with a compound of formula H2N-R3 (VI), wherein R3 has the same significance as defined above for the compounds of formula (II), and which is known or may be produced analogously to methods known per se, in the presence of an excess of formaldehyde or paraformaldehyde.
A further object of the invention is d) a method of producing a compound of formula (I), and optionally the E/Z
isomers, E/Z
isomeric mixtures and/or tautomers thereof, each in free form or in salt form, characterised _g_ in that a compound of formula (V) is converted into a compound of formula (III) by reacting it with a compound of formula (VI) and formaldehyde or paraformaldehyde; this compound of formula (III) is converted into a compound of formula (II) by a compound of formula (IV), and this compound of formula (II) is hydrolysed.
A further object of the invention is e) the use of the compounds of formula (II) in the preparation of the compounds of formula (I).
Preferred embodiments of the method according to variants b) to d) may be taken from the examples.
The starting compounds or starting products of formulae (II) and (III) considered for the method according to the invention, and optionally the possible E/Z isomers, E/Z isomeric mixtures and/or tautomers thereof, each in free form or in salt form, are new.
They similarly form an object of the invention.
The compounds of formula (I) which are produced according to the invention are valuable active ingredients in pest control, that are well tolerated by warm-blooded animals, fish and plants. The compounds of formula (I) are especially suitable for the control of insects and arachnids, which appear on crops and ornamentals in agriculture, especially in cotton, vegetable and fruit plantations, in forestry, in the protection of stock and material, as well as in the hygiene sector, especially on domestic animals and productive livestock. The compounds are especially effective against plant-damaging sucking insects, especially against aphids and plant and leaf hoppers. Pesticidally active substituted 2-nitroguanidines of the type that may be produced according to the invention are described e.g.
in EP patent applications 376.279, 375.907 and 383.091.
Preparation examples Example P1.1: Preparation of the compound of formula H
N-O N~N~ -/N-n-C~8H3~
z N
i A mixture of 2.4 g of 1-methyl-2-nitroguanidine, 5.5 g of octadecylamine, 20 ml of ethanol and 3.2 ml of a 37% solution of formaldehyde in water is heated to 50°C
and stirred at this temperature for 4 hours. The mixture is then evaporated to dryness under vacuum, the residue stirred with diethyl ether and the title compound isolated by filtration (compound 1.10).
Example P1.2: Preparation of the compound of formula H
N~ ~CH2 N~ N
02N, N~
i A mixture of 3.54 g of 1-methyl-2-nitroguanidine, 2.7 ml of allylamine, 50 ml of toluene and 2.7 g of paraformaldehyde is mixed with 3 drops of concentrated hydrochloric acid and heated for 20 hours on a water separator. Then, the mixture is evaporated to dryness under vacuum, the residue taken up with dichloromethane/methanol (98:2), filtered over silica gel and the filtrate concentrated by evaporation. The title compound is obtained by recrystallisation from isopropanol with a melting point of 53-55 °C
(compound 1.14).
Example P1.3: Preparation of the compound of formula H
N
N- N
02N N ~ -N
i A mixture of 5.9 g of 1-methyl-2-nitroguanidine, 5.2 g of 3-aminopyridine, 4.5 g of para-formaldehyde, 60 ml of dioxane and 0.24 g of p-toluenesulfonic acid is heated for 20 hours on a water separator. After cooling, the reaction mixture is filtered and the residue of filtration is washed with dimethylformamide and toluene. This yields the title compound with a melting point of 204-208°C (compound 1.26).
The following compounds of formula (III) listed in Table 1 can also be obtained analogously to the above methods of examples P1.1 to P1.3.
Table 1: Compounds of formula ~N~
,N N~ (Illa) H ~ CH3 N
~
No. R3 phys. data 1.1 cyclooctyl 1.2 cyclodecyl 1.3 cycloheptyl 1.4 -(CH2),o-CH3 1.5 -(CH2)"-CH3 m.p. 85-87 C
1.6 -(CH2),2-CH3 1.7 -(CH2),3-CH3 1.8 -(CH2),4-CH3 1.9 -(CH2), 5-CH3 1.10 -(CH2),~-CH3 1.11 -(CH2)8-CH=CH-(CH2),-CH3 (cis) 1.12 -(CHZ),o-COOH
1.13 -(CHZ)"-COOH m.p. 93-95 C
PI/5-30128/A ca o23om2 Zooo-o2-is No. R3 phys. data 1.14 -CH2-CH=CH2 m.p. 53-55 °C
1.15 -CH-(CH20H)CH(OH)-CH=CH-(CH2)~z-CH3 1.16 -CH2-CH=CH(CH3)-(CHz)2-CH=C(CH3)2 1.17 -CH-(CH20H)CH(OH)-C---C-(CH2),2-CH3 1.18 -(CH2)s-C=C-CsHs 1.19 -CHZ-C---C-C6H5 1.20 \ \ \
1.21 1.22 / / /
\ \ \
1.23 naphth-1-yl 1.24 naphth-2-yl 1.25 thiazol-2-yl 1.26 pyrid-3-yl m.p. 204-208 °C
1.27 pyrid-4-yl 1.28 3-bromonaphth-2-yl PI/5-30128/A ca o23om2 Zooo-o2-is No. R3 phys. data 1.29 1-hydroxy-naphth-2-yl 1.30 4-methoxy-naphth-2-yl 1.31 5-hydroxy-naphth-2-yl 1.32 1-chloronaphth-2-yl 1.33 8-nitronapht-2-yl 1.34 -NHCOOC2H5 m.p. 203-204 °C
1.35 m.p. 156-158 °C
O
O
1.36 O
~NH
1.37 cyclododecyl m.p. 137-139 °C
1.38 O m.p. 56-57 °C
I ~ ~~~~H2~"
CI
1.39 -CH2)"-C(=O)OCH3 m.p. 91-94 °C
Example P2.1: Preparation of the compound of formula N
~N~ ~N n-ClsHs~
N
CI
PI/5-30128/A ca o23om2 Zooo-o2-is A mixture of 6.0 g of the compound obtainable according to example P1.1, 2.8 g of 2-chloro-5-chloromethylpyridine and 4.8 g of potassium carbonate in 20 ml of dimethylformamide is stirred for 10 hours at 50 °C. Then, the reaction mixture is filtered, the filtrate concentrated by evaporation under vacuum, and the recrystallised from ethanol. This yields the title compound with a melting point of 95-97°C (compound 10.8.1 ).
The following compounds of formula (II) listed in Tables 2 to 13 can also be obtained analogously to the above method of example P2.1.
Table A Compounds of formula /N\
A~N~N~ (Ila), H N
A.1 cyclooctyl CH=C(CH3)2 A.2 cyclodecyl A.17 -CH-(CH20H)CH(OH)-C---C-A.3 cycloheptyl (CH2),2-CH3 A.4 -(CH2),o-CH3 A.18 -(CH2)s-C=C-CsHs A.5 -(CH2)"-CH3 A.19 -CH2-C---C-C6H5 A.6 -(CHz),2-CH3 A.20 / / /
A.7 -(CH2)~3-CH3 A.8 -(CH2pa-CH3 \ \ \
A.9 -(CH2), 5-CH3 A.10 -(CH2)»-CH3 A.21 A.11 -(CH2)a-CH=CH-(CHZ)~-CH3 (cis) A.12 -(CH2),o-COOH
A.13 -(CH2)"-COOH
A.14 -CH2-CH=CH2 A.22 A.15 -CH-(CHZOH)CH(OH)-CH=CH-(CH2),z-CH3 \ \ \
A.16 -CH2-CH=CH(CH3)-(CH2)2- A.23 naphth-1-yl PI/5-30128/A ca o23om2 Zooo-o2-is No. R -. No. Rs A.24 naphth-2-yl A.35 A.25 thiazol-2-yl O
A.26 pyrid-3-yl O
A.27 pyrid-4-yl A.36 O
A.28 3-bromonaphth-2-yl A.29 1-hydroxy-naphth-2-yl ~NH
A.30 4-methoxy-naphth-2-yl A.31 5-hydroxy-naphth-2-yl A.37 cyclododecyl A.32 1-chloronaphth-2-yl A.38 O
A.33 8-nitro-naphth-2-yl i \ 0..
-/ (CH2)~W
4.34 -NHCOOC2H5 CI S
A.39 -CH2)1~-C(=O)OCH3 S
Table 2: Compounds of the general formula (Ila), wherein A signifies ~I~~ and !/N
R3 corresponds in each case to one line of Table A.
Compound 2.A.5: m.p. 119-121 C
Compound 2.A.37: m.p. 137-139 C
Compound 2.A.38: m.p. 76-78 C
Compound 2.A.39: m.p. 90-92 C
S
Table 3: Compounds of the general formula (Ila), wherein A signifies < ~ and N
corresponds in each case to one line of Table A.
Br Table 4: Compounds of the general formula (Ila), wherein A signifies ~ ~ and N
R3 corresponds in each case to one line of Table A.
HsC S
Table 5: Compounds of the general formula (Ila), wherein A signifies N
and R3 corresponds in each case to one line of Table A.
Table 6: Compounds of the general formula (Ila), wherein A signifies O
and R3 corresponds in each case to one line of Table A.
Table 7: Compounds of the general formula (Ila), wherein A signifies ~ and R3 O
corresponds in each case to one line of Table A.
CI
Table 8: Compounds of the general formula (Ila), wherein A signifies ~ ~ and N-O
R3 corresponds in each case to one line of Table A.
Table 9: Compounds of the general formula (Ila), wherein A signifies CI ~ / and R3 corresponds in each case to one line of Table A.
N
Compound 9.A.10: m.p. 95-97C.
Compound 9.A.14: m.p. 75-77C.
Compound 9.A.26: m.p. 222C.
Compound 9.A.34: m.p. 200C.
Compound 9.A.35: m.p. 178-180 C.
Compound 9.A.36: m.p. 214 C.
Table 10: Compounds of the general formula (Ila), wherein A signifies ~ and N
R3 corresponds in each case to one line of Table A.
PI/5-30128/A ca o23om2 Zooo-o2-is Table 11: Compounds of the general formula (Ila), wherein A signifies N and I+
O
R3 corresponds in each case to one line of Table A.
Table 12: Compounds of the general formula (Ila), wherein A signifies CI \N
I+
O
and R3 corresponds in each case to one line of Table A.
CI
Table 13: Compounds of the general formula (Ila), wherein A signifies CI N
and R3 corresponds in each case to one line of Table A.
Example 3.1: Preparation of the compound of formula H H ~ CI
I I
H C~N~N / N
'I3 N
~ N02 4.0 g of the compound obtainable according to example P2.1 are stirred for 16 hours at 50°
C in 20 ml of methanol and 25 ml of 1 n hydrochloric acid. The reaction mixture is filtered and the residue of filtration washed with methanol and dried. This yields the title product with a melting point of 147-149°C (compound 14.6).
The following compounds of formula (I) listed in Table 14 can also be obtained analogously to the above method of example P3.1.
PI/5-30128/A ca o23om2 Zooo-o2-is Table 14: Compounds of the general formula N-H CI) N
N
H A
No. A Phys.data 14.1 G
N
14.2 H3C
N
14.3 /
N
14.4 Br N
14.5 O
m.p. 147-149°C
14.6 CI
N
14.7 /
CI N.~.
I_ O
14.8 CI /
~J
CI N
14.9 N
PI/5-30128/A ca o23om2 Zooo-o2-is No. A Phys.data 14.10 H3C
O
14.11 CI
N-O
14.12 /
N
I+
O
A further object of the invention is f) a method of controlling pests, especially animal pests, particularly insects and members of the order Acarina, using the compounds of formula (II). The said animal pests include, for example, those that are mentioned in the European Patent application EP-A-736'252. The pests mentioned therein are thus included by reference in the object of the present invention. The method of controlling the said pests and the composition and preparation of the corresponding pesticides are described in EP-A-736'252 and are included by reference in the object of the present invention.
Claims (10)
1. Method of producing a compound of formula wherein R1 is hydrogen or C1-C4-alkyl;
R2 is hydrogen, C1-C6-alkyl, C3-C6-cycloalkyl or a radical -CH2B;
A is an aromatic or non-aromatic, monocyclic or bicyclic heterocyclic radical which is unsubstituted or - depending on the substitution possibilities of the ring system - mono- to penta-substituted by substituents selected from the group comprising halogen, C1-C3-alkyl, C1-C3-alkoxy, halogen-C1-C3-alkyl, C1-C3-halogenalkoxy, cyclopropyl, halogencyclopropyl, C2-C3-alkenyl, C2-C3-alkynyl, C2-C3-halogenalkenyl and C2-C3-halogenalkynyl, C1-C3-alkylthio, C1-C3-halogenalkylthio, allyloxy, propargyloxy, allylthio, propargylthio, halogenallyloxy, halogenallylthio, cyano and nitro; and B is phenyl, 3-pyridyl or thiazolyl, which are optionally substituted by one to three substituents from the group comprising C1-C3-alkyl, C1-C3-halogenalkyl, cyclopropyl, halogencyclopropyl, C2-C3-alkenyl, C2-C3-alkynyl, C1-C3-alkoxy, C2-C3-halogenalkenyl, C2-C3-halogenalkynyl, C1-C3-halogenalkoxy, C1-C3-alkylthio, C1-C3-halogenalkylthio, allyloxy, propargyloxy, allylthio, propargylthio, halogenallyloxy, halogenallylthio, halogen, cyano and nitro;
and, if appropriate, the possible E/Z isomers, E/Z isomeric mixtures and/or tautomers thereof, each in free form or in salt form;
characterised in that a compound of formula wherein R1, R2 and A have the same significances as given for formula (I), and R3 is unsubstituted or substituted C11-C22-alkyl, C7-C16-cycloalkyl, C3-C20-alkenyl, C3-C20-alkynyl, N(R4)R5, optionally substituted aryl except for unsubstituted and substituted phenyl; or an optionally substituted, aromatic or non-aromatic, monocyclic or bicyclic, heterocyclic radical;
R4 is hydrogen or C1-C12-alkyl;
R5 is hydrogen, C1-C12-alkyl, C1-C12-alkyl-carbonyl or C1-C12-alkoxy-carbonyl, is hydrolysed.
R2 is hydrogen, C1-C6-alkyl, C3-C6-cycloalkyl or a radical -CH2B;
A is an aromatic or non-aromatic, monocyclic or bicyclic heterocyclic radical which is unsubstituted or - depending on the substitution possibilities of the ring system - mono- to penta-substituted by substituents selected from the group comprising halogen, C1-C3-alkyl, C1-C3-alkoxy, halogen-C1-C3-alkyl, C1-C3-halogenalkoxy, cyclopropyl, halogencyclopropyl, C2-C3-alkenyl, C2-C3-alkynyl, C2-C3-halogenalkenyl and C2-C3-halogenalkynyl, C1-C3-alkylthio, C1-C3-halogenalkylthio, allyloxy, propargyloxy, allylthio, propargylthio, halogenallyloxy, halogenallylthio, cyano and nitro; and B is phenyl, 3-pyridyl or thiazolyl, which are optionally substituted by one to three substituents from the group comprising C1-C3-alkyl, C1-C3-halogenalkyl, cyclopropyl, halogencyclopropyl, C2-C3-alkenyl, C2-C3-alkynyl, C1-C3-alkoxy, C2-C3-halogenalkenyl, C2-C3-halogenalkynyl, C1-C3-halogenalkoxy, C1-C3-alkylthio, C1-C3-halogenalkylthio, allyloxy, propargyloxy, allylthio, propargylthio, halogenallyloxy, halogenallylthio, halogen, cyano and nitro;
and, if appropriate, the possible E/Z isomers, E/Z isomeric mixtures and/or tautomers thereof, each in free form or in salt form;
characterised in that a compound of formula wherein R1, R2 and A have the same significances as given for formula (I), and R3 is unsubstituted or substituted C11-C22-alkyl, C7-C16-cycloalkyl, C3-C20-alkenyl, C3-C20-alkynyl, N(R4)R5, optionally substituted aryl except for unsubstituted and substituted phenyl; or an optionally substituted, aromatic or non-aromatic, monocyclic or bicyclic, heterocyclic radical;
R4 is hydrogen or C1-C12-alkyl;
R5 is hydrogen, C1-C12-alkyl, C1-C12-alkyl-carbonyl or C1-C12-alkoxy-carbonyl, is hydrolysed.
2. Method according to claim 1 of producing a compound of formula (I) in free form.
3. Method according to one of claims 1 or 2 of producing a compound of formula (I) wherein R1 is hydrogen.
4. Method according to one of claims 1 to 3 of producing a compound of formula (I), wherein R2 is hydrogen, C1-C3-alkyl or cyclopropyl.
5. Method according to one of claims 1 to 4 of producing a compound of formula (I) from a compound of formula (II), wherein R3 is C11-C16-alkyl; C11-C18-alkyl substituted by hydroxy or -COO-C1-C16-alkyl; C3-C18-alkenyl optionally substituted by phenyl or hydroxy; C3-C18-alkynyl optionally substituted by phenyl;
cyclooctyl, cyclodecyl, cycloheptyl, cyclododecyl, thiazolyl, pyridyl, pyridinyl, pyrazinyl or optionally substituted naphthyl.
cyclooctyl, cyclodecyl, cycloheptyl, cyclododecyl, thiazolyl, pyridyl, pyridinyl, pyrazinyl or optionally substituted naphthyl.
6. Method according to one of claims 1 to 5 of producing a compound of formula (I) wherein A is 2-chloropyrid-5-yl, tetrahydrofuran-3-yl, 5-methyl-tetrahydrofuran-3-yl or 2-chlorothiazol-5-yl.
7. Method according to one of claims 1 to 6 of producing a compound of formula (I), characterised in that the pH value lies between 7 and 12.
8. Method according to one of claims 1 to 6 of producing a compound of formula (I), characterised in that the pH value lies between 5 and 1.
9. A method of producing a compound as defined in claim 1, formula (II), and optionally the E/Z isomers, E/Z isomeric mixtures and/or tautomers thereof, each in free form or in salt form, characterised in that a compound of formula wherein R2 and R3 are as defined above in claim 1 for formula (II); and optionally the E/Z
isomers, E/Z isomeric mixtures and/or tautomers thereof, each in free form or in salt form, is reacted with a compound of formula wherein R1 and A are defined as in claim 1 for formula (I), and Y is a leaving group.
isomers, E/Z isomeric mixtures and/or tautomers thereof, each in free form or in salt form, is reacted with a compound of formula wherein R1 and A are defined as in claim 1 for formula (I), and Y is a leaving group.
10. A method of producing a compound as defined in claim 9, formula (III), and optionally the E/Z isomers, E/Z isomeric mixtures and/or tautomers thereof, each in free form or in salt form, characterised in that a compound of formula wherein R2 has the same significance as defined in claim 1 for formula (I), is reacted with a compound of formula H2N-R3 (VI), wherein R3 has the same significance as defined in claim 1 for the compounds of formula (II), in the presence of an excess of formaldehyde or paraformaldehyde.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1951/97 | 1997-08-20 | ||
| CH195197 | 1997-08-20 | ||
| PCT/EP1998/005248 WO1999009009A1 (en) | 1997-08-20 | 1998-08-18 | Method for producing organic compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2301172A1 true CA2301172A1 (en) | 1999-02-25 |
Family
ID=4222414
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA002301172A Abandoned CA2301172A1 (en) | 1997-08-20 | 1998-08-18 | Method for the producing substituted-2-nitroguanidine derivatives |
Country Status (12)
| Country | Link |
|---|---|
| EP (1) | EP1005456A1 (en) |
| JP (1) | JP2001515066A (en) |
| KR (1) | KR20010023053A (en) |
| CN (1) | CN1271346A (en) |
| AU (1) | AU741658B2 (en) |
| BR (1) | BR9811966A (en) |
| CA (1) | CA2301172A1 (en) |
| HU (1) | HUP0003632A3 (en) |
| ID (1) | ID24319A (en) |
| IL (1) | IL134502A0 (en) |
| PL (1) | PL338778A1 (en) |
| WO (1) | WO1999009009A1 (en) |
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| DE19806469A1 (en) * | 1998-02-17 | 1999-08-19 | Bayer Ag | Preparation of 2-nitroguanidine derivatives useful as insecticides and acaricides |
| KR20010041996A (en) * | 1998-03-19 | 2001-05-25 | 한스 루돌프 하우스, 헨리테 브룬너, 베아트리체 귄터 | Process for the preparation of nitroguanidine derivatives |
| DE19961604A1 (en) * | 1999-12-21 | 2001-07-05 | Bayer Ag | Process for the preparation of 1,3-disubstituted 2-nitroguanidines |
| DE10121652A1 (en) * | 2001-05-03 | 2002-11-07 | Bayer Ag | Process for the preparation of 1,3-disubstituted 2-nitroguanidines |
| WO2003017764A1 (en) * | 2001-08-23 | 2003-03-06 | Bayer Cropscience S.A. | Substituted propargylamines |
| CN102070629A (en) * | 2010-12-28 | 2011-05-25 | 上海师范大学 | Novel nicotine and clothianidin analogue pesticide and preparation method thereof |
| CN103254171A (en) * | 2013-04-16 | 2013-08-21 | 中国农业大学 | Aromatic heterocyclic triazine (trans)-delta-farnesene analogue and application thereof |
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| JP2779403B2 (en) * | 1988-11-29 | 1998-07-23 | 日本バイエルアグロケム株式会社 | Insecticidal nitro compounds |
| IE960442L (en) * | 1988-12-27 | 1990-06-27 | Takeda Chemical Industries Ltd | Guanidine derivatives, their production and insecticides |
| DK0383091T3 (en) * | 1989-02-13 | 1994-02-07 | Bayer Agrochem Kk | Insecticidal active nitro compounds |
| AU6044790A (en) * | 1989-07-28 | 1991-03-11 | Nippon Soda Co., Ltd. | Triazine derivatives |
| AU628229B2 (en) * | 1989-11-10 | 1992-09-10 | Agro-Kanesho Co. Ltd. | Hexahydrotriazine compounds and insecticides |
| JPH0674249B2 (en) * | 1990-04-05 | 1994-09-21 | アグロカネショウ株式会社 | Method for producing substituted nitroguanidines |
| IL99576A0 (en) * | 1990-10-05 | 1992-08-18 | Ciba Geigy Ag | Triazacyclohexane derivatives |
| TW198724B (en) * | 1990-10-24 | 1993-01-21 | Ciba Geigy Ag | |
| JP2766848B2 (en) * | 1993-10-26 | 1998-06-18 | 三井化学株式会社 | Furanyl insecticides |
| JP3258502B2 (en) * | 1993-10-26 | 2002-02-18 | 三井化学株式会社 | Insecticidal tetrahydrofuran derivative |
-
1998
- 1998-08-18 JP JP2000509693A patent/JP2001515066A/en active Pending
- 1998-08-18 EP EP98946375A patent/EP1005456A1/en not_active Withdrawn
- 1998-08-18 CA CA002301172A patent/CA2301172A1/en not_active Abandoned
- 1998-08-18 CN CN98809316A patent/CN1271346A/en active Pending
- 1998-08-18 WO PCT/EP1998/005248 patent/WO1999009009A1/en not_active Application Discontinuation
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- 1998-08-18 AU AU93442/98A patent/AU741658B2/en not_active Ceased
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- 1998-08-18 BR BR9811966-4A patent/BR9811966A/en not_active IP Right Cessation
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Also Published As
| Publication number | Publication date |
|---|---|
| HUP0003632A2 (en) | 2001-02-28 |
| CN1271346A (en) | 2000-10-25 |
| JP2001515066A (en) | 2001-09-18 |
| IL134502A0 (en) | 2001-04-30 |
| PL338778A1 (en) | 2000-11-20 |
| BR9811966A (en) | 2000-08-15 |
| ID24319A (en) | 2000-07-13 |
| AU741658B2 (en) | 2001-12-06 |
| KR20010023053A (en) | 2001-03-26 |
| AU9344298A (en) | 1999-03-08 |
| EP1005456A1 (en) | 2000-06-07 |
| HUP0003632A3 (en) | 2002-11-28 |
| WO1999009009A1 (en) | 1999-02-25 |
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