Process for preparing amidrazones

The present invention relates to a process for preparing amidrazones of formula I

wherein

R is hydrogen, d-Cε-alkyl, Ci-Cβ-alkoxycarbonyl, Ci-Cβ-alkylaminocarbonyl or di(Ci-C6-alkyl)-aminocarbonyl;

R ¹ is Ci-Cio-alkyl, C ₃ -Cio-alkenyl, C ₃ -Cio-alkynyl, C ₃ -Ci ₂ -cycloalkyl, di(Ci-Ce-alkyl)- amino, Ci-C6-alkylsulfonyl or Ci-Cβ-alkylsulfinyl;

R ² is Ci-Cio-alkyl, C2-Cio-alkenyl, C2-Cio-alkynyl, C3-Ci2-cycloalkyl wherein in each of the above radicals the alkyl, alkenyl, alkynyl or cycloalkyl groups are unsubstituted or partially or fully halogenated and/or substituted with

1 to 3 substituents independently selected from cyano, nitro, hydroxy, mercapto, amino, d-Cε-alkyl, Cs-Cβ-cycloalkyl, Ci-Cβ-alkoxy, Ci-Cβ- alkylamino, di(Ci-C6-alkyl)-amino, Ci-C6-alkylthio, Ci-C6-alkylsulfonyl and Ci-Cβ-alkylsulfinyl, wherein in each of the above radicals the alkyl or cycloalkyl groups are unsubstituted or substituted with

1 to 3 halogen atoms or a ring system selected from phenoxy, a 5- to 6-membered aromatic ring which may contain 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen and a 3- to 6-membered saturated or partially unsaturated ring which contains 1 to 3 heteroatoms selected from oxygen, sulfur and nitrogen, with each ring being unsubstituted or substituted with 1 to 5 substituents independently selected from halogen, d-Cε-alkyl, C-i-Ce-alkylthio, Ci-C ₆ -alkylsulfonyl, Ci-C ₆ -alkylsulfinyl, C-i-Cβ-alkoxy, nitro and cyano, wherein in each of the above substituents the alkyl group is unsubstituted or substituted with 1 to 3 halogen atoms, or

is a 3- to 6-membered saturated or partially unsaturated ring which may contain 1 to 3 heteroatoms selected from oxygen, sulfur and nitrogen and which is unsubstituted or substituted with 1 to 5 substituents independently selected from

halogen, d-Cε-alkyl, C-i-Cε-alkylthio, Ci-Cβ-alkylsulfonyl, Ci-Cβ-alkylsulfinyl, d-Cβ-alkoxy, C-i-Cβ-haloalkoxy, nitro and cyano, wherein in each of the above radicals the alkyl group is unsubstituted or substituted with 1 to 3 halogen atoms;

A is C-R ³ or N; B is C-R ⁴ Or N; W is C-R ⁵ or N;

with the proviso that one of A, B and W is other than N;

R ³ , R ⁴ , R ⁵ are each independently hydrogen, halogen, nitro, cyano, amino, mercapto, hydroxy, Ci-Cio-alkyl, C2-Cio-alkenyl, C2-Cio-alkynyl, Cs-drcycloalkyl, d-Cβ-alkoxy, Ci-Cβ-alkylamino, di(Ci-C6-alkyl)-amino, C-i-Cβ-alkylthio, Ci-Cβ-alkylsulfonyl, Ci-Cβ-alkylsulfinyl or a 5- to 6-membered aromatic ring which may contain 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen;

Y is hydrogen, halogen, cyano, nitro, amino, hydroxy, mercapto, Ci-Cβ-alkyl,

C2-Cio-alkenyl, C2-Cio-alkynyl, Cs-drcycloalkyl, Ci-Cβ-alkoxy, Ci-Cβ-alkylamino, di(Ci-C6)-alkylamino, Ci-dralkylthio, Ci-Cβ-alkylsulfonyl, or Ci-Cβ-alkylsulfinyl; and n is O, 1 , or 2

or a salt thereof .

Amidrazones are useful pest control agents, e.g. as described in EP-A 604 798, and also in J. A Furch et al., "Amidrazones: A New Class of Coleopteran Insecticides", ACS Symposium Series 686, Am. Chem. Soc, 1998, Chapter 18, pp. 178; and D. G. Kuhn et al., "Cycloalkyl-substituted Amidrazones: A Novel Class of Insect Control Agents", ACS Symposium Series 686, Am. Chem. Soc, 1998, Chapter 19, pp. 185.

Each of these references describes the preparation of a broad range of amidrazones by the route as shown in the following scheme:

(4) (5) (6)

This synthesis route involves reacting a substituted arylhydrazine (1) with an appropriate acid chloride (2) in the presence of a base to obtain the arylhydrazide (3). The arylhydrazide (3) is then reacted with a halogenating agent such as, for example, thionylchloride to give the arylhydrazinoyl halide (4). The reaction of the arylhydrazinoyl halide (4) with the amine (5) yields the desired amidrazone (6).

The known route starts from the relatively expensive arylhydrazine (1), which is undesirable due to the corresponding losses in yield during the subsequent reaction steps. Another problem of the known preparation process is the isolation of the amidrazone (6) in pure or relatively pure form. This can only be achieved through laborious purification of the precursor arylhydrazinoyl halide (4) such as, for example, by silica filtration. In addition, a further purification of the final product through its hydrochloride salt may be required, which causes additional costs.

It is also known in the art that only a few specific amidrazone derivatives can be prepared by reacting aryl hydrazines with imide derivatives.

J. Beger et al., Monatshefte fuer Chemie, Vol. 1 12, No. 8-9, 1981 , pp. 959-971 , discloses the synthesis of certain 1-phenylamino-2-imidazolines and 1 ,2,5,6-tetrahydro- 1 ,2,4-triazines from N-(2-chloroalkyl)-imide chlorides and phenylhydrazines via amidrazones hydrochlorides as intermediates. The provided amidrazone hydrochlorides show a great tendency to undergo spontaneous cyclization to the heterocyclic compounds. Further, the preparation of the amidrazone hydrochlorides disclosed therein requires excess amounts of the expensive phenylhydrazine as starting material which is undesirable from the point of view of costs. Despite the use of such excess amounts, the described process leads to low yields relative to the phenylhydrazine.

P. Nuhn et al., Pharmazie, Vol. 48, No. 5, 1993, pp. 340-342, discloses the reaction of certain open-chain aryl-substituted amidrazones by reaction of N-aryl benzimide chlorides with arylhydrazines. However, the isolation of the amidrazones by repeated crystallization is difficult due to the presence of undesired by-products, resulting in low yield and purity of the final product.

Thus, there remains a need to provide an economical and industrially feasible process for the preparation of the specific amidrazones of the formula I or a salt thereof which affords the compounds I or a salt thereof in high yields and high purity.

Surprisingly, it has now been found that the specific amidrazones of formula I or a salt thereof are obtained in high yields and high purity when an arylhydrazine of formula Il

wherein R, A, B, W, Y and n are each as defined above, is reacted with an imidoyl compound of formula III

wherein R ¹ and R ² are each as defined above and X ¹ is halogen, d-Cβ-alkoxy, C-i-Cβ-alkylsulfonate, C-i-Cβ-haloalkylsulfonate, C-i-Cε-alkylthio, d-Cβ-alkylphosphate, or C6-Ci2-arylphosphate, optionally in the presence of a base.

The present invention therefore provides a process for preparing the amidrazones of formula I or a salt thereof, comprising reacting an arylhydrazine of formula Il with an imidoyl compound of formula III, optionally in the presence of a base.

Another advantage of the inventive process is that relatively cheap starting materials can be used for the production of the imidoyl compound of formula III as the second reactant.

The imidoyl compound of formula III can be obtained in a similar manner to the known prior art methods from an amide of formula IV

wherein R ¹ and R ² are each as defined above, by reacting the amide IV with an agent capable of converting the amide IV into the imidoyl compound III. Accordingly, the process according to the invention preferably also comprises the preparation of the imidoyl compound of formula III by this route.

The imidoyl compounds of the formula III are novel wherein

R ¹ is Ci-Cio-alkyl, Cs-do-alkenyl, Cs-do-alkynyl, C ₃ -Ci ₂ -cycloalkyl, di(Ci-Ce-alkyl)- amino, Ci-Cβ-alkylsulfonyl or Ci-Cβ-alkylsulfinyl, wherein in each of the above radicals the alkyl, alkenyl, alkynyl or cycloalkyl groups are unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, C-i-Cβ-alkoxy, C-i-Cβ-haloalkoxy, C-i-Cε-alkylthio, C-i-Cε-haloalkylthio, Ci-Cβ-alkylsulfonyl, Ci-Cβ-alkylsulfinyl, Ci-Cβ-haloalkylsulfonyl, Ci-Cβ-haloalkylsulfinyl, Cs-Cβ-cycloalkyl, phenyl and pyridyl;

R ² is cyclopropyl which is substituted with 1 to 3 halogen atoms and/or 1 to 3 Ci-Cβ- alkyl groups and/or 1 to 3 C-i-Cε-haloalkyl groups; and

X ¹ is halogen, Ci-Cβ-alkoxy, C-i-Cβ-alkylsulfonate, C-i-Cβ-haloalkylsulfonate, C6-Ci2-arylsulfonate, C-i-Cε-alkylthio, C-i-Cβ-alkylphosphate, or

Therefore, these compounds likewise form part of the subject matter of the present invention as starting materials or intermediates in the process according to the invention.

Further, the amide of the formula IV used in the process for the preparation of the imidoyl compounds III may in turn be obtained in a similar manner to the known prior art processes from a compound of formula V

wherein X ² is a suitable leaving group and R ² is as defined above, by reacting the compound V with an amine of formula Vl

R ⁱ -NH ₂ (Vl)

wherein R ¹ is as defined above. Accordingly, the process according to the invention preferably also comprises the preparation of the amides of the formula IV by this route.

The amides of the formula IV are novel wherein

R ¹ is Ci-Cio-alkyl, C ₃ -Cio-alkenyl, C ₃ -Cio-alkynyl, C ₃ -Ci ₂ -cycloalkyl, di(Ci-C ₆ -alkyl)- amino, Ci-C6-alkylsulfonyl or C i -Cβ-a I ky I s u If i ny I , wherein in each of the above radicals the alkyl, alkenyl, alkynyl or cycloalkyl groups are unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, d-Cβ-alkoxy, d-Cβ-haloalkoxy, d-Cβ-alkylthio, d-Cβ-haloalkylthio, Ci-Cβ-alkylsulfonyl, d-Cβ-alkylsulfinyl, d-Cβ-haloalkylsulfonyl, Ci-Cβ-haloalkylsulfinyl, C ₃ -C6-cycloalkyl, phenyl and pyridyl;

R ² is a cyclopropyl group of formula VII

wherein R ⁶ is d-Cβ-alkyl, R ⁷ and R ⁸ are both halogen, and R ⁹ and R ¹⁰ are both hydrogen.

Accordingly, these compounds are also contemplated by the present invention as starting materials or intermediates in the process according to the invention.

In the definitions of the variables specified in the above formulae I to VII, collective terms are used which are generally representative of particular substituents. The term Ca-Cb specifies the number of carbon atoms in the particular substituents or substituent moiety which is possible in each case. Other definitions are as follows:

"Halogen" will be taken to mean fluorine, chlorine, bromine, and iodine.

The term "halo" refers to fluoro, chloro, bromo, and iodo.

The term "alkyl" as used herein refers to a branched or unbranched saturated hydrocarbon group having 1 to 10 carbon atoms, especially Ci-Cβ-alkyl such as methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1 ,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1 ,1-dimethylpropyl, 1 ,2-dimethylpropyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1 ,1-dimethylbutyl, 1 ,2-dimethylbutyl, 1 ,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl,

1 ,1 ,2-trimethylpropyl, 1 ,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1 -ethyl-2- methyl propyl.

The term "haloalkyl" as used herein refers to a straight-chain or branched alkyl groups having 1 to 10 carbon atoms (as mentioned above), where some or all of the hydrogen atoms in these groups may be replaced by halogen atoms as mentioned above, for example Ci-C2-haloalkyl, such as chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2- difluoroethyl, 2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl and pentafluoroethyl.

Similarly, "alkoxy" and "alkylthio" refer to straight-chain or branched alkyl groups having 1 to 6 carbon atoms (as mentioned above) bonded through oxygen or sulfur linkages, respectively, at any bond in the alkyl group. Examples include methoxy, ethoxy, propoxy, isopropoxy, methylthio, ethylthio, propylthio, isopropylthio, and n-butylthio.

Similarly, "alkylsulfinyl", "alkylsulfonyl" and "alkylsulfonate" refer to straight-chain or branched alkyl groups having 1 to 6 carbon atoms (as mentioned above) bonded through -S(=O)-, -S(=O)2- or -S(=O)2-O- linkages, respectively, at any bond in the alkyl group. Examples include methylsulfinyl, methylsulfonyl and methylsulfonate.

Similarly, "alkylamino" refers to a nitrogen atom which carries 1 or 2 straight-chain or branched alkyl groups having 1 to 6 carbon atoms (as mentioned above) which may be the same or different. Examples include methylamino, dimethylamino, ethylamino, diethylamino, methylethylamino, isopropylamino, or methylisopropylamino.

The term "alkylcarbonyl" refers to straight-chain or branched alkyl groups having 1 to 6 carbon atoms (as mentioned above) bonded through a -C(=O)- linkage, respectively, at any bond in the alkyl group. Examples include acetyl and propionyl.

The term "alkenyl" as used herein intends a branched or unbranched unsaturated hydrocarbon group having 3 to 10 carbon atoms and a double bond in any position, such as C3-C6 alkenyl such as 1-propenyl, 2-propenyl, 1-methyl-ethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 2-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-2-propenyl; 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1- butenyl, 2-methyl-1-butenyl, 3-methyl-1-butenyl, 1-methyl-2-butenyl, 2-methyl-2- butenyl, 3-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3- butenyl, 1 ,1-dimethyl-2-propenyl, 1 ,2-dimethyl-1-propenyl, 1 ,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl,

5-hexenyl, 1-methyl-1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1- pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2-pentenyl, 4-methyl-2-

pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3- pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4- pentenyl, 1 ,1-dimethyl-2-butenyl, 1 ,1-dimethyl-3-butenyl, 1 ,2-dimethyl-1-butenyl, 1 ,2-dimethyl-2-butenyl, 1 ,2-dimethyl-3-butenyl, 1 ,3-dimethyl-1-butenyl, 1 ,3-dimethyl-2- butenyl, 1 ,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl,

2,3-dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1 -butenyl, 3,3-dimethyl-2- butenyl, 1-ethyl-1 -butenyl, 1-ethyl-2-butenyl, 1-ethyl-3-butenyl, 2-ethyl-1 -butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1 ,1 ,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2- propenyl, 1-ethyl-2-methyl-1-propenyl and 1-ethyl-2-methyl-2-propenyl.

The term "alkynyl" as used herein refers to a branched or unbranched unsaturated hydrocarbon group containing at least one triple bond, such as ethynyl, propynyl, 1-butynyl, 2-butynyl and the like.

"Cycloalkyl" refers to a monocyclic 3- to 8-, 10- or 12-membered saturated carbon atom rings, e.g. Cs-Cs-cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl.

The term "aryl" refers to an aromatic carbocyclic group having at least one aromatic ring (e.g., phenyl or biphenyl) or multiple condensed rings in which at least one ring is aromatic, (e.g., 1 ,2,3,4-tetrahydronaphthyl, naphthyl, anthryl, or phenanthryl), each of which may be substituted.

A 5- to 6-membered aromatic ring containing 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen, intends e.g. 5-membered heteroaryl, containing 1 to 4 nitrogen atoms or 1 to 3 nitrogen atoms and 1 sulfur or oxygen atom, e.g. fury I, thienyl, pyrrolyl, isoxazolyl, isothiazolyl, pyrazolyl, oxazolyl, thiazolyl, imidazolyl, oxadiazolyl, thiadiazolyl, oxadiazolyl, triazolyl, and tetrazolyl; or 6-membered heteroaryl, containing 1 to 4 nitrogen atoms or 1 to 3 nitrogen atoms and 1 sulfur or oxygen atom, e.g. 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 3-pyridazinyl, 4-pyridazinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-pyrazinyl, 1 ,3,5-triazin-2-yl and 1 ,2,4-triazin-3-yl.

A 3- to 6-membered saturated or partially unsaturated ring which contains 1 to 3 heteroatoms selected from oxygen, sulfur and nitrogen intends e.g. a saturated 3- to 6- membered ring containing 1 to 3 heteroatoms selected from nitrogen and oxygen, such as aziridine, pyrrolidine, tetrahydrofuran, tetrahydropyran, or piperidine.

A "suitable leaving group" is any group which can be displaced at the carbon atom by nucleophiles such as nitrogen, oxygen, sulfur, etc. or the anions of these nucleophiles under the reaction conditions of the process of the present invention such as, for example, halogen (e.g. fluorine, chlorine, and bromine), hydroxy, alkoxy, alkylcarboxylate (e.g. acetate), benzoate, alkylsulfonate (e.g. mesylate),

haloalkylsulfonate (e.g. trifluoromethylsulfonate), arylsulfonate (e.g. tosylate), alkylthio, alkylphosphate (e.g. diethylphosphate) and arylphosphate. Preferred leaving groups are halogen and Ci-Cβ-alkoxy. Examples of halogen are fluorine, chlorine, and bromine, with chlorine being preferred. Preference is also given to Ci-C4-alkoxy, more preferably methoxy, ethoxy, propoxy, butoxy and isobutoxy, in particular methoxy or ethoxy, with methoxy being most preferred.

The arylhydrazines of formula Il are known and can be prepared according to methods described in the art, for example by E. Enders in Houben-Weyl, Vol. X/2 (Stickstoffverbindungen I), Georg Thieme Verlag, Stuttgart, 1967, pp. 169 et sqq. The process as described in DE-A 34 47 21 1 may also be used for preparing the a ryl hydrazine II.

To react the arylhydrazine Il with the imidoyl compound III, the compounds will be used preferably in a molar ratio of Il :l 11 in the range of from 1 :1.1 to 1 :1.4, in particular from 1 :1.3 to 1 :1.2 and more preferably from 1 :1.1 to 1 :1.

The arylhydrazine Il is advantageously reacted with the imidoyl compound III at temperatures of at least 20 ⁰ C, for example in the range from 25°C to 90 ⁰ C and in particular from 40 ⁰ C to 80°C. The reaction pressure is of minor importance for the success of the process according to the invention and thus the reaction of arylhydrazine Il with the imidoyl compound III can be carried out under reduced pressure, under normal pressure (i.e. atmospheric pressure) or under increased pressure. Preference is given to carrying out the reaction in the region of atmospheric pressure, for example in the range from 0.9 to 1.2 bar. The reaction time can be varied in a wide range and depends on a variety of factors including the heat transfer capacity of the used equipment. The reaction time required for the reaction is generally in the range from 1 to 10 hours, in particular 1 to 5 hours.

The reaction may in principle be carried out in substance. However, preference is given to reacting the arylhydrazine Il with the imidoyl compound III in an organic solvent. Suitable solvents are in principle any which are capable of at least partly and preferably fully dissolving the arylhydrazine Il and the imidoyl compound III under reaction conditions. Preferred solvents are aprotic. They are in particular those solvents that have a boiling point at atmospheric pressure in the range from 35 °C to 160 ⁰ C and in particular in the range of 60 ⁰ C to 130 °C. Preferred solvents are aliphatic and aromatic solvents, in particular aliphatic and aromatic hydrocarbons, halogenated aliphatic and aromatic hydrocarbons, heterocyclic aromatic compounds and mixtures thereof. Particularly preferred solvents are aromatic hydrocarbons, especially alkylbenzenes and even more preferably alkylbenzenes which are mono-, di-, or trial kylsubstituted with each alkyl group containing 1 to 3 carbon atoms, such as, for example, toluene, xylenes (i.e. m-xylene, o-xylene, p-xylene, and mixtures thereof), ethylbenzene,

2-propylbenzene (cumene), 2-isopropyltoluene (o-cymol), 3-isopropyltoluene (m-cymol), 4-isopropyltoluene (p-cymol), 1 ,3,5-trimethylbenzene (mesitylene) and mixtures thereof, with toluene being the most preferred. Halogenated aromatic hydrocarbons and heterocyclic aromatic compounds are also preferred. Examples of halogenated aromatic hydrocarbons include chlorobenzene, bromobenzene, o-dichlorobenzene, m-dichlorobenzene and mixtures thereof, with preference being given to chlorobenzene. Examples of suitable heterocyclic aromatic compounds include pyridine, 5-ethyl-2-methyl-pyridine, 2-methylpyridine, 3-methylpyridine, 4-methylpyridine and mixtures thereof.

The arylhydrazine II, the imidoyl compound III and optionally the base may be contacted together in any suitable manner. In general, the arylhydrazine II, the imidoyl compound III and optionally the base will be initially charged in a reaction vessel, if appropriate together with the solvent desired, and then the desired reaction conditions will be established. In a preferred embodiment, however, the major amount, especially at least 80 % and more preferably the total amount or virtually the total amount (at least 95%) of the arylhydrazine Il may also be charged into a reaction vessel, if appropriate in the desired solvent. The base may then be added thereto and the desired reaction conditions will be established. Following this the major amount, preferably at least 80 % and more preferably the total amount or virtually the total amount (at least 95%) of the imidoyl compound III is added thereto under reaction conditions in the course of the reaction. The imidoyl compound III can be added as such or preferably in the desired solvent.

The arylhydrazine Il can be reacted with the imidoyl compound III in the presence or in the absence of a base. It is preferred, however, that the reaction of the arylhydrazine Il with the imidoyl compound III is carried out in the presence of a base to obtain the amidrazones of formula I. Suitable bases used in this reaction are inorganic compounds, such as, for example, alkali metal hydroxides, alkali hydrogen carbonates, alkali carbonates, alkaline earth metal hydroxides, carbonates or bicarbonates, and alkali hydrides. Advantageously, organic bases, such as tertiary amines, can be used. Preference is given to tertiary amines represented by the formula N(R ¹¹ )(R ¹² )(R ¹³ ) wherein R ¹¹ , R ¹² and R ¹³ are the same or different and each represents a straight chain or branched chain alkyl or cycloalkyl radical having 1 to 8 carbon atoms, such as methyl, ethyl, propyl, butyl, isopropyl, t-butyl, amyl, cyclohexyl and the like. Examples of suitable tertiary amines are trimethylamine, triethylamine, tripropylamine, triisopropylamine, tri-n-butylamine, tri-sec-butylamine, tri-t-butylamine, tri-n-octylamine, diisopropylethylamine, and dicyclohexylethylamine. Particular preference is given to tri- n-butylamine, diisopropylethylamine and dicyclohexylethylamine. It has been found to be particularly advantageous to use tri-n-butylamine as the base, which has an economically attractive price, is easy to recover from aqueous waste streams and

allows to perform the reaction of the arylhydrazine Il with the imidoyl compound III in homogeneous solution in a wide range solvents.

Advantageously, the base is employed in a stoichiometric amount or in a slight excess, relative to the arylhydrazine of formula II. Preferably, the base is present in an amount of 1 to 1.5 moles, in particular 1 to 1.3 moles and more preferably 1 to 1.2 moles, relative to 1 mole of the arylhydrazine II.

In the case of conducting the reaction in the absence of a base, a salt of the amidrazone of formula I is obtained, said salt comprising an anionic counterion derived from the moiety X ¹ as defined hereinabove, in particular halogenides, alkylsulfonates, haloalkylsulfonates, arylsulfonates, alkylphosphates, or arylphosphates. Preferred salts are halogenides, in particular chlorides.

In case of reacting the arylhydrazine Il with the imidoyl compound III in the presence of a base, the resulting amidrazone I (that is, a compound having a basic nitrogen atom at the amine moiety) may subsequently be reacted with a suitable acid to form an acid addition salt of the amidrazone I. "Acid-addition salts" include conventional salts formed from suitable organic or inorganic acids. Exemplary acid-addition salts formed by the compounds of formula I include chlorides, bromides, fluorides, hydrogen sulfates, sulfates, dihydrogen phosphates, hydrogen phosphates, phosphates, nitrates, hydrogen carbonates, carbonates, hexafluorosilicates, hexafluorophosphates, benzoates, and the salts of Ci-C4-alkanoic acids, preferably formates, acetates, propionates and butyrates. Preferred acid-addition salts are chlorides and hydrogen sulfates.

The amidrazones of formula I can be isolated from the reaction mixture by employing conventional methods, for example by adding water to the reaction mixture, extracting with an organic solvent, concentrating the extract and the like. If the base is employed in an excess relative to arylhydrazine II, an acid (e.g. hydrochloric acid, sulphuric acid and the like) is advantageously added to neutralize the excessive base. In case of preparing a salt of the amidrazones I, isolation may be effected by conventional methods such as filtration.

The process according to the present invention may also lead to isomers of the amidrazones of formula I as defined herein. The term "isomer" is used herein in its broadest sense to include structural isomers (such as, for example, positional isomers and tautomers) and stereoisomers (such as, for example, optical isomers, rotational isomers and E/Z isomers). In cases where the amidrazones of formula I possess asymmetric carbon atoms, the process according to the present invention may result in the racemates and diastereomers as well as the individual enantiometric forms of the amidrazones I as described herein. Mixtures of isomers can be separated into

individual isomers according to methods customary for this purpose, e.g. fractional crystallization, adsorption chromatography or other suitable separation processes. Resulting racemates can be separated into antipodes in the usual manner after introduction of suitable salt-forming groupings, e.g. by forming a mixture of diastereosiomeric salts with optically active salt-forming agents, separating the mixture into diastereomeric salts and converting the separated salts into the free compounds. The possible enantiomeric forms may also be separated by fractionation through chiral high performance liquid chromatography columns.

The imidoyl compound of the general formula III used in the process according to the invention can be prepared in a similar manner to the prior art methods for preparing imidoyl compounds by reacting the amide of formula IV with an agent capable of converting the amide IV into the imidoyl compound III, for example in a similar manner to the methods described in Chem. Ber. 93 (1960), pp. 1231-1236 or Liebigs Ann. Chem. 716 (1968), pp. 127-134.

Examples of suitable agents capable of converting the amide IV into the imidoyl compound III are halogenating agents, O-alkylating agents, phosphating agents and sulfonylating agents. Preferred agents for use in the invention are halogenating agents.

For example, if the desired imidoyl compound III is one wherein X ¹ is halogen, the amide of formula IV is reacted with an appropriate halogenating agent, preferably a chlorinating or brominating agent. Examples of suitable halogenating agents include thionyl chloride, phosgene, oxalyl chloride, sulfuryl chloride, p-toluenesulfonyl chloride, methanesulfonyl chloride, phosphorus pentachloride, phosphorus oxychloride, phosphorus trichloride, thionyl bromide, phosphorus pentabromide, phosphorus tribromide, phosphorus oxybromide and methanesulfonyl bromide. Even more preferred are thionyl chloride, phosgene and oxalyl chloride, with thionyl chloride being the most preferred.

If the desired imidoyl compound III is one wherein X ¹ is d-Cβ-alkoxy, it is possible to react the amide of formula IV with an O-alkylating agent. Suitable O-alkylating agents include, for example, trialkyloxonium salts such as triethyloxonium tetrafluoroborate.

Further, if the desired imidoyl compound III is one wherein X ¹ is C-i-Cβ-alkylphosphate or C6-Ci2-arylphosphate, the amide of formula IV is reacted with an appropriate phosphating agent. As the phosphating agent, phosphoric acid chlorides such as dialkylphosphoric acid chlorides (e.g. diethylphosphoric acid chloride) may be used.

Moreover, if the desired imidoyl compound III is one wherein X ¹ is C-i-Cβ-alkylsulfonate, Ci-Cβ-haloalkylsulfonate or the amide of formula IV is reacted with an appropriate sulfonylating agent. Examples of suitable sulfonylating agents include

alkylsulfonic acid anhydrides, haloalkylsulfonic acid anhydrides, arylsulfonic acid anhydrides, alkylsulfonic acid chlorides, haloalkylsulfonic acid chlorides, and arylsulfonic acid chlorides, such as p-toluenesulfonyl chloride or mesitylenesulfonyl chloride.

If the desired imidoyl compound III is one wherein X ¹ is d-Cε-alkylthio, it can be prepared by converting the amide of formula IV into the corresponding thioamide by treatment with Lawesson's reagent and reacting the thioamide obtained therefrom with an alkylating agent. As the alkylating agent, an alkyl halogenide such as methyl iodide may be used.

In a preferred embodiment of this invention, the amide of formula IV is reacted with a halogenating agent, in particular with any of the halogenating agents specified above and more preferably with a halogenating agent selected from thionyl chloride, phosgene and oxalyl chloride, with thionyl chloride being preferred.

In general, the agent capable of converting the amide IV into the imidoyl compound III will be used in an amount of 1 to 5 moles, in particular 1.2 to 3 moles and more preferably 1.2 to 2 moles, relative to 1 mole of the amide IV.

The reaction of the amide of formula IV with the agent capable of converting the amide IV into the imidoyl compound III is preferably carried out at temperatures of at least 0 ⁰ C, for example in the range from 10 ⁰ C to 85°C and preferably from 40 ⁰ C to 85°C. The reaction pressure is of minor importance for the success of the reaction and thus the reaction can be conducted under reduced pressure, normal pressure (i.e. atmospheric pressure) or increased pressure. The reaction is preferably carried out in the region of atmospheric pressure, for example in the range from 0.9 to 1.2 bar. The reaction time required for the reaction is generally in the range from 2 to 20 hours, in particular from 4 to 20 hours and more preferably from 4 to 15 hours.

The reaction may in principle be carried out in substance. However, preference is given to reacting the amide IV with the agent capable of converting the amide IV into the imidoyl compound III in an organic solvent. As to the type of organic solvents suitable for this reaction, reference is made to the solvents as described hereinabove in connection with the reaction of the arylhydrazine Il with the imidoyl compound III.

For the reaction, the amide IV may be brought into contact with the agent capable of converting the amide IV into the imidoyl compound III in any suitable manner. In general, the amide IV and said agent will be initially charged in a reaction vessel, if appropriate together with the solvent desired, and then the desired reaction conditions will be established. In a preferred embodiment, however, the major amount, preferably at least 80 % and more preferably the total amount or virtually the total amount (at least

95%) of amide IV may also be charged into a reaction vessel, if appropriate in the desired solvent. The major amount, preferably at least 80 % and more preferably the total amount or virtually the total amount (at least 95%) of the agent capable of converting the amide IV into the imidoyl compound III is then added under reaction conditions in the course of the reaction, if appropriate in the desired solvent.

The amide of the formula IV used in the process for the preparation of the imidoyl compounds III can in turn be obtained in a similar manner to the known prior art processes for preparing amides by reacting the compound of formula V with an amine of formula Vl, for example in a similar manner to the methods as described in Organikum, 21th Ed., Wiley-VCH, Weinheim 2001 , pp. 481-488.

The compounds V used to prepare the amides IV are known and processes for their preparation can be found, for example, in Organikum, 21th Ed., Wiley-VCH, Weinheim 2001 , pp. 498-499.

If not commercially available, the amine of formula Vl can be obtained according to literature procedures readily available to those skilled in the art, e.g. by reductive amination of carbonyl compounds or hydrogenation of nitro compounds as described, for example, in Organikum, 21th Ed., Wiley-VCH, Weinheim 2001 , pp. 584-585 and 626-629.

To react the compound V with the amine Vl, the compounds will preferably be used in a molar ratio of V:VI in the range from 1 :1 to 1 :10, in particular 1 :2 to 1 :4 and more preferably from 1 :2 to 1 :3.

The compound V is advantageously reacted with the amine Vl at temperatures of at least 0 ⁰ C, in particular in the range from 0 ⁰ C to 80 ⁰ C, more preferably from 10 ⁰ C to 70 ⁰ C and even more preferably from 40 ⁰ C to 60 ⁰ C. The reaction pressure is of minor importance for the success of the reaction and thus the reaction can be conducted under reduced pressure, normal pressure (i.e. atmospheric pressure) or increased pressure. The reaction is preferably carried out in the region of atmospheric pressure, for example in the range from 0.9 to 1.2 bar. The reaction time required for the reaction can be varied in a wide range and depends on a variety of factors including the capacity of heat transfer of the used equipment. In general, the reaction time is in the range from 1 to 10 hours, in particular 1 to 5 hours.

The reaction may in principle be carried out in substance. In a preferred embodiment, however, the compound V is reacted with the amine Vl in an organic solvent. As to the type of organic solvents suitable for this reaction, reference is made to the solvents as described hereinabove in connection with the reaction of the arylhydrazine Il with the imidoyl compound III. Moreover, protic solvents such as an alcohol or water may be

used. The use of protic solvents, especially water, depends on the reactivity of the used amine Vl. For example, if the amine Vl is ethylamine, it is possible to use an aqueous solution of ethylamine.

For the reaction, the compound V and the amine Vl may be contacted together in any suitable manner. In general, the compound V and the amine Vl will be initially charged into a reaction vessel, if appropriate together with the solvent desired, and then the desired reaction conditions will be established. In a preferred embodiment, however, the major amount, preferably at least 80 % and more preferably the total amount or virtually the total amount (at least 95%) of the amine Vl is placed into a reaction vessel, optionally in the desired solvent. The major amount, preferably at least 80 % and more preferably the total amount or virtually the total amount (at least 95%) of the compound V is then added to the amine Vl under reaction conditions in the course of the reaction. The compound V can be added as such or preferably in the desired solvent.

A preferred embodiment of the invention relates to a process comprising the steps of

(a) reacting the compound of formula V with the amine of formula Vl as described herein to obtain the amide of formula IV, (b) reacting the amide of formula IV with an agent capable of converting the amide IV into the imidoyl compound III as described herein to obtain the imidoyl compound of formula III, and

(c) reacting the imidoyl compound of formula III with the arylhydrazine of formula Il as described herein, optionally in the presence of a base, to obtain the amidrazones of formula I or a salt thereof.

Another advantage of the process according to the invention is that the amidrazones I can be obtained in a high yield and purity, without isolation of the intermediates of formulae III and IV and purification measures of these intermediates being required. Thus, in a preferred embodiment, the steps (a)+(b) or (b)+(c) or (a)+(b)+(c) as defined above are carried out in a one-pot procedure without isolating the amide of formula IV and/or the imidoyl compound of formula III. In a particularly preferred embodiment, the steps (a), (b) and (c) are carried out in a one-pot procedure without isolating the amide of formula IV and the imidoyl compound of formula III. However, it is also contemplated by this invention that the amide IV can be isolated after the step (a) by conventional methods, for example distillation, recrystallization and the like. The imidoyl compound III may also be isolated after step (b) in the same manner as above.

It is also preferred that each of the steps in the sequences (a)+(b) or (b)+(c) or (a)+(b)+(c) is carried out in the same solvent selected from those solvents described hereinabove. Preference is given to aprotic solvents, in particular aromatic hydrocarbons, halogenated aromatic hydrocarbons and heterocyclic aromatic

compounds, with aromatic hydrocarbons being preferred. In a particularly preferred embodiment, toluene, chlorobenzene or pyridine is used as a solvent in each of the steps in the sequences (a)+(b) or (b)+(c) or (a)+(b)+(c), with preference being given to toluene.

If desired, the amidrazone I, the amide IV and the imidoyl compound III can be purified independently after their isolation by using techniques that are known in the art, for example by distillation, recrystallization and the like.

The overall process according to this invention has several advantages when compared to the prior art processes. The inventive process enables the introduction of the relatively expensive arylhydrazine of formula Il in the very last step of the synthesis sequence, i.e. step (c). As this step is performed with a high yield and purity, the process of the present invention is highly efficient in terms of cost of goods. Moreover, the process can be conducted in ecologically friendly solvents. Since the reaction steps (a), (b) and (c) of the inventive process can be carried out in a one-pot procedure, there is no need for isolation and tedious purification of the intermediates (IV) and/or (III). Instead, it is possible to conduct any sequence of reaction steps with in situ prepared intermediates.

The advantages of the process according to the invention become particularly apparent when, in the compounds of formulae I to Vl, the variables and indices are each independently defined as follows, more preferably in combination:

A in the formulae I and Il denotes C-R ³ ;

B in the formulae I and Il denotes C-R ⁴ ;

W in the formulae I and Il denotes C-R ⁵ ;

Y in the formulae I and Il is halogen or d-Cβ-haloalkyl, more preferably halogen or Ci-Cβ-haloalkyl which is disposed in the 6-position;

Y in the formulae I and Il is halogen, in particular halogen which is disposed in the 6-position;

Y in the formulae I and Il is chlorine, in particular chlorine which is disposed in the 6-position;

n in the formulae I and Il is 1 ;

R in the formulae I and Il is hydrogen, d-Cβ-alkyl, d-Cβ-alkoxycarbonyl, d-Cβ-alkylaminocarbonyl or di(Ci-C6-alkyl)-aminocarbonyl, wherein in each of the above radicals the alkyl group is unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, cyano, nitro, d-Cβ-alkoxy, C2-C6-alkenyloxy, C2-C6-alkynyloxy, d-Cβ-haloalkoxy, d-Cβ-alkylthio, d-Cβ-haloalkylthio, Ci-Cβ-alkylsulfonyl, d-Cβ-alkylsulfinyl and di(Ci-C6alkyl)-amino;

R in the formulae I and Il is hydrogen or d-Cβ-alkyl, in particular hydrogen;

R ¹ in the formulae I, III, IV and Vl is Ci-Cio-alkyl, drdo-alkenyl, drdo-alkynyl, C3-Ci2-cycloalkyl, di(d-C6-alkyl)-amino, Ci-C6-alkylsulfonyl, or Ci-Cβ-alkylsulfinyl, wherein in each of the above radicals the alkyl, alkenyl, alkynyl or cycloalkyl groups are unsubstituted or substituted with 1 to 3 substituents independently selected from halogen, nitro, cyano, d-Cβ-alkoxy, d-Cβ-haloalkoxy, d-Cβ-alkylthio, d-Ce-haloalkylthio, d-Ce-alkylsulfonyl, d-Ce-alkylsulfinyl, d-Ce-haloalkylsulfonyl, Ci-Cβ-haloalkylsulfinyl, Cs-Cβ-cycloalkyl, phenyl, and pyridyl;

R ¹ in the formulae I, III, IV and Vl is d-do-alkyl which is unsubstituted or substituted by d-d-alkoxy or is C3-do-cycloalkyl which is unsubstituted or substituted with from 1 to 3 halogen;

R ¹ in the formulae I, III, IV and Vl is d-C ₆ -alkyl or C ₃ -C ₆ -cycloalkyl;

R ¹ in the formulae I, III, IV and Vl is d-d-alkyl, in particular ethyl;

R ² in the formulae I, III, IV and V is d-do-alkyl, in particular d-Cβ-alkyl and with tert- butyl being most preferred;

R ² in the formulae I, III, IV and V is C3-Ci2-cycloalkyl wherein the cycloalkyl group is unsubstituted or partially or fully halogenated and/or substituted with

1 to 3 substituents independently selected from cyano, nitro, hydroxy, mercapto, amino, d-Cβ-alkyl, Cs-Cβ-cycloalkyl, d-Cβ-alkoxy, d-Cβ-alkylamino, di(d-C6-alkyl)- amino, d-Cβ-alkylthio, d-Cβ-alkylsulfonyl and d-Cβ-alkylsulfinyl, wherein in each of the above radicals the alkyl or cycloalkyl groups are unsubstituted or substituted with

1 to 3 halogen atoms or a ring system selected from phenoxy, a 5- to 6- membered aromatic ring which may contain 1 to 4 heteroatoms selected from oxygen, sulfur and nitrogen and a 3- to 6-membered saturated or partially unsaturated ring which contains 1 to 3 heteroatoms selected from oxygen, sulfur and nitrogen, with each ring being unsubstituted or

substituted with 1 to 5 substituents independently selected from halogen, d-Ce-alkyl, Ci-C ₆ -alkylthio, d-Ce-alkylsulfonyl, d-Ce-alkylsulfinyl, d-Cβ-alkoxy, nitro and cyano, wherein in each of the above substituents the alkyl group is unsubstituted or substituted with 1 to 3 halogen atoms;

R ² in the formulae I, III, IV and V is C3-do-cycloalkyl which is unsubstituted or substituted with 1 to 5 halogen atoms and/or 1 to 3 d-C6-alkyl groups and/or 1 to 3 d-Cβ-haloalkyl groups;

R ² in the formulae I, III, IV and V is cyclopropyl which is unsubstituted or substituted with 1 to 3 halogen atoms and/or 1 to 3 d-C6-alkyl groups and/or 1 to 3 d-Cβ-haloalkyl groups;

R ² in the formulae I, III, IV and V is cyclopropyl which is substituted with 2 halogen atoms and/or 1 Ci-C6-alkyl group;

R ² in the formulae I, III, IV and V is cyclopropyl which is substituted with 2 chlorine atoms and/or 1 methyl group;

R ² in the formulae I, III, IV and V is a cyclopropyl group of formula VII

wherein R ⁶ is hydrogen, d-Ce-alkyl or d-Ce-haloalkyl, and R ⁷ , R ⁸ , R ⁹ and R ¹⁰ are each independently selected from hydrogen, halogen, Ci-C6-alkyl and d-Cβ-haloalkyl;

R ² in the formulae I, III, IV and V is a cyclopropyl group of formula VII wherein R ⁶ is hydrogen, d-Ce-alkyl or Ci-Ce-haloalkyl, R ⁷ and R ⁸ are both halogen, and R ⁹ and R ¹⁰ are both hydrogen;

R ² in the formulae I, III, IV and V is a cyclopropyl group of formula VII wherein R ⁶ is Ci-Cβ-alkyl, R ⁷ and R ⁸ are both halogen, and R ⁹ and R ¹⁰ are both hydrogen;

R ² in the formulae I, III, IV and V is a cyclopropyl group of formula VII wherein R ⁶ is hydrogen, methyl or trifluoromethyl, R ⁷ and R ⁸ are independently selected from fluoro, chloro and bromo, and R ⁹ and R ¹⁰ are both hydrogen;

R ² in the formulae I, III, IV and V is a cyclopropyl group of formula VII wherein R ⁶ is hydrogen or methyl, R ⁷ and R ⁸ are chloro or bromo, and R ⁹ and R ¹⁰ are both hydrogen;

R ² in the formulae I, III, IV and V is a cyclopropyl group of formula VII wherein R ⁶ is methyl, R ⁷ and R ⁸ are chloro or bromo, and R ⁹ and R ¹⁰ are both hydrogen;

R ² in the formulae I, III, IV and V is a cyclopropyl group of formula VII wherein R ⁶ is methyl, R ⁷ and R ⁸ are both chloro, and R ⁹ and R ¹⁰ are both hydrogen, i.e. 1-(2,2- dichloro-1 -methylcyclopropyl);

R ³ is halogen or d-Cε-haloalkyl, preferably halogen, especially chlorine or bromine, with chlorine being most preferred;

R ⁴ is hydrogen or halogen, especially hydrogen;

R ⁵ is halogen or C-i-Cβ-haloalkyl, preferably C-i-Cβ-haloalkyl, especially trifluoromethyl;

X ¹ in the formula III is halogen, more preferably chlorine or bromine and especially chlorine;

X ² in the formula V is halogen or Ci-Cβ-alkoxy;

X ² in the formula V is halogen, in particular chlorine or bromine and especially chlorine; X ² in the formula V is Ci-Cβ-alkoxy, preferably Ci-C4-alkoxy, more preferably methoxy, ethoxy, propoxy, butoxy and isobutoxy, especially methoxy or ethoxy, with methoxy being most preferred;

For the process according to the invention, it has been found to be particularly advantageous when A in the formulae I and Il is C-R ³ wherein R ³ is halogen or

C-i-Cε-haloalkyl, B in the formulae I and Il is C-R ⁴ wherein R ⁴ is hydrogen or halogen, W in the formulae I and Il is C-R ⁵ wherein R ⁵ is halogen or C-i-Cβ-haloalkyl, Y in the formulae I and Il is a halogen atom in the 6 position of the aromatic ring, n in the formulae I and Il is 1 , R in the formulae I and Il is hydrogen or Ci-Cβ-alkyl, R ¹ in the formulae I, III, IV and Vl is Ci-C4-alkyl, R ² in the formulae I, III, IV and V is a cyclopropyl group of formula VII as defined hereinabove wherein R ⁶ is hydrogen, Ci-Cβ-alkyl or Ci-Cβ-haloalkyl, and R ⁷ , R ⁸ , R ⁹ and R ¹⁰ are each independently selected from hydrogen, halogen, Ci-Cβ-alkyl and C-i-Cβ-haloalkyl, X ¹ in the formula III is halogen, and X ² in the formula V is halogen or Ci-Cβ-alkoxy.

In an even more preferred embodiment, A in the formulae I and Il is C-Cl, B in the formulae I and Il is CH, W in the formulae I and Il is C-CF3, Y in the formulae I and Il is a chlorine atom in the 6 position of the aromatic ring, n in the formulae I and Il is 1 , R in

the formulae I and Il is hydrogen, R ¹ in the formulae I, III, IV and Vl is ethyl, R ² in the formulae I, III, IV and V is 1-(2,2-dichloro-1-methylcyclopropyl), X ¹ in the formula III is chlorine, and X ² in the formula V is chlorine or methoxy.

Moreover, preference is given to imidoyl compounds of formula III used as starting materials or intermediates in the process according to the invention wherein the variables R ¹ , R ² and X ¹ are each independently defined as follows, more preferably in combination:

R ¹ is Ci-Cio-alkyl, in particular Ci-C4-alkyl and especially ethyl;

R ² is a cyclopropyl group of formula VII as defined hereinabove wherein R ⁶ is hydrogen, d-Cε-alkyl or d-Cε-haloalkyl, R ⁷ and R ⁸ are both halogen, and R ⁹ and R ¹⁰ are both hydrogen, more preferably a cyclopropyl group of formula VII wherein R ⁶ is C-i-Cε-alkyl, R ⁷ and R ⁸ are both halogen, and R ⁹ and R ¹⁰ are both hydrogen, even more preferably a cyclopropyl group of formula VII wherein R ⁶ is hydrogen, methyl or trifluoromethyl, R ⁷ and R ⁸ are independently selected from fluoro, chloro and bromo, and R ⁹ and R ¹⁰ are both hydrogen, yet even more preferably a cyclopropyl group of formula VII wherein R ⁶ is hydrogen or methyl, R ⁷ and R ⁸ are chloro or bromo, and R ⁹ and R ¹⁰ are both hydrogen, still even more preferably a cyclopropyl group of formula VII wherein R ⁶ is methyl, R ⁷ and R ⁸ are chloro or bromo, and R ⁹ and R ¹⁰ are both hydrogen and especially a cyclopropyl group of formula VII wherein R ⁶ is methyl, R ⁷ and R ⁸ are both chloro, and R ⁹ and R ¹⁰ are both hydrogen, i.e. 1-(2,2-dichloro-1- methylcyclopropyl);

X ¹ is halogen, Ci-Cβ-alkoxy, C-i-Cβ-alkylsulfonate, C-i-Cβ-haloalkylsulfonate, C6-Ci2-arylsulfonate, C-i-Cε-alkylthio, C-i-Cβ-alkylphosphate or C6-Ci2-arylphosphate, more preferably halogen, in particular chlorine or bromine, with chlorine being preferred.

Preference is also given to imidoyl compounds of formula III wherein R ¹ is Ci-Cio-alkyl, in particular Ci-C4-alkyl and especially ethyl, R ² is a cyclopropyl group of formula VII as defined hereinabove wherein R ⁶ is hydrogen, Ci-Cβ-alkyl or d-Cε-haloalkyl, R ⁷ and R ⁸ are both halogen, R ⁹ and R ¹⁰ are both hydrogen, and X ¹ is halogen, in particular chlorine or bromine, with chlorine being preferred.

Preference is also given to imidoyl compounds of formula III wherein R ¹ is Ci-Cio-alkyl, in particular Ci-C4-alkyl and especially ethyl, R ² is a cyclopropyl group of formula VII as defined hereinabove wherein R ⁶ is d-Cε-alkyl, R ⁷ and R ⁸ are both halogen, and R ⁹ and R ¹⁰ are both hydrogen, and X ¹ is halogen, in particular chlorine or bromine, with chlorine being preferred.

Preference is also given to imidoyl compounds of formula III wherein R ¹ is Ci-Cio-alkyl, in particular Ci-C4-alkyl and especially ethyl, R ² is a cyclopropyl group of formula VII as defined hereinabove wherein R ⁶ is hydrogen, methyl or trifluoromethyl, R ⁷ and R ⁸ are independently selected from fluoro, chloro and bromo, and R ⁹ and R ¹⁰ are both hydrogen, and X ¹ is halogen, in particular chlorine or bromine, with chlorine being preferred.

Preference is also given to compounds of formula III wherein R ¹ is Ci-Cio-alkyl, in particular Ci-C4-alkyl and especially ethyl, R ² is a cyclopropyl group of formula VII as defined hereinabove wherein R ⁶ is hydrogen or methyl, R ⁷ and R ⁸ are independently selected from chloro and bromo, and R ⁹ and R ¹⁰ are both hydrogen, and X ¹ is halogen, especially chlorine or bromine, with chlorine being preferred.

Preference is also given to compounds of formula III wherein R ¹ is Ci-Cio-alkyl, in particular Ci-C4-alkyl and especially ethyl, R ² is 1-(2,2-dibromo-1-methylcyclopropyl) or 1-(2,2-dichloro-1-methylcyclopropyl) and X ¹ is halogen, especially chlorine or bromine, with chlorine being preferred.

Particularly preferred is a compound of formula III wherein R ¹ is ethyl, R ² is 1-(2,2- dichloro-1-methylcyclopropyl) and X ¹ is chlorine, i.e. 2,2-Dichloro-N-ethyl-1-methyl- cyclopropanecarboximidoyl chloride (see formula III' below).

("I" ¹ )

This invention also relates to the use of the imidoyl compound of formula III (and especially compound III') as a starting material or an intermediate for the preparation of amidrazones or a salt thereof, in particular the amidrazones of formula I or a salt thereof.

Also, preference is given to amides of formula IV used as starting materials or intermediates in the process according to the invention wherein the variables R ¹ and R ² are each independently defined as follows, more preferably in combination:

R ¹ is Ci-Cio-alkyl, in particular Ci-C4-alkyl and especially ethyl;

R ² is a cyclopropyl group of formula VII as defined hereinabove wherein R ⁶ is Ci-Cβ- alkyl, R ⁷ and R ⁸ are both halogen, and R ⁹ and R ¹⁰ are both hydrogen, more preferably a cyclopropyl group of formula VII wherein R ⁶ is hydrogen, methyl or trifluoromethyl, R ⁷ and R ⁸ are independently selected from fluoro, chloro and bromo, and R ⁹ and R ¹⁰ are both hydrogen, even more preferably a cyclopropyl group of formula VII wherein R ⁶ is hydrogen or methyl, R ⁷ and R ⁸ are chloro or bromo, and R ⁹ and R ¹⁰ are both hydrogen, yet even more preferably a cyclopropyl group of formula VII wherein R ⁶ is methyl, R ⁷ and R ⁸ are chloro or bromo, and R ⁹ and R ¹⁰ are both hydrogen and especially a cyclopropyl group of formula VII wherein R ⁶ is methyl, R ⁷ and R ⁸ are both chloro, and R ⁹ and R ¹⁰ are both hydrogen, i.e. 1-(2,2-dichloro-1-methylcyclopropyl).

Preference is also given to amides of formula IV wherein R ¹ is Ci-Cio-alkyl, in particular Ci-C4-alkyl and especially ethyl and R ² is a cyclopropyl group of formula VII wherein R ⁶ is d-Cε-alkyl, R ⁷ and R ⁸ are both halogen, and R ⁹ and R ¹⁰ are both hydrogen.

Preference is also given to amides of formula IV wherein R ¹ is Ci-Cio-alkyl, in particular Ci-C4-alkyl and especially ethyl and R ² is a cyclopropyl group of formula VII as defined hereinabove wherein R ⁶ is hydrogen, methyl or trifluoromethyl, R ⁷ and R ⁸ are independently selected from fluoro, chloro and bromo, and R ⁹ and R ¹⁰ are both hydrogen.

Preference is also given to amides of formula IV wherein R ¹ is Ci-Cio-alkyl, in particular Ci-C4-alkyl and especially ethyl and R ² is a cyclopropyl group of formula VII as defined hereinabove wherein R ⁶ is hydrogen or methyl, R ⁷ and R ⁸ are independently selected from chloro and bromo, and R ⁹ and R ¹⁰ are both hydrogen.

Preference is also given to amides of formula IV wherein R ¹ is Ci-Cio-alkyl, in particular Ci-C4-alkyl and especially ethyl and R ² is 1-(2,2-dibromo-1-methylcyclopropyl) or 1 -(2,2-dichloro-1 -methylcyclopropyl).

Particularly preferred is an amide of formula IV wherein R ¹ is ethyl and R ² is 1-(2,2- dichloro-1 -methylcyclopropyl), i.e. 2,2-dichloro-1 -methyl-cyclopropane-carboxylic-acid ethylamide (see formula IV below).

(IV)

This invention also relates to the use of the amide of formula IV (and especially compound IV) as a starting material or an intermediate for the preparation of amidrazones or a salt thereof, in particular the amidrazones of formula I or a salt thereof.

Although the imidoyl compound III and the amide IV are useful starting materials or intermediates for the preparation of amidrazones, their use as starting materials or intermediates for the preparation of other products likewise forms part of the scope of protection of this invention.

The process according to the invention will be illustrated, in case of preparing 2,2- dichloro-N'-(2,6-dichloro-4-trifluoromethylphenyl)-N-ethyl-1 -methylcyclopropane- carbohydrazonamide (I') via the intermediates (IN') and (IV), by the following reaction scheme:

toluene

(V) (Vl ¹ ) (IV)

(IV)

toluene

(I ¹ )

In addition to the general methods described above for the preparation of the compounds of formula V, the compounds V wherein R ² is a dichlorocyclopropyl group (e.g. 2,2-dichloro-1-methylcyclopropyl) may also be prepared by the following procedure: (1 ) reaction of dichlorocarbene with conjugated dienes, e.g. with 2-methyl- 1 ,3-butadiene (isoprene), to give the corresponding addition product (e.g. 2,2-dichloro- 1-methyl-1-vinylcyclopropane), (2) oxidation of the addition product with potassium permanganate in acetone at 0 ⁰ C to yield the corresponding carboxylic acid (e.g. 2,2-dichloro-1-methylcyclopropane-1 -carboxylic acid) and (3) conversion of the carboxylic acid into the corresponding acid chloride, e.g. with SOCb/benzene. This sequence of reaction steps (1 ), (2) and (3) has been reported in Toke, S. M. and

Kulkarni, G. H., Indian Journal of Chemistry, Vol. 3OB, January 1991 , pp. 82-84. The sequence of steps (1 ) and (2) can also be found in M. Orchin and E. C. Herrick, J. Org. Chem., 24 (1959), pp. 139-140. The carboxylic acid used in step (3) hereinabove can also be obtained by dichlorocarbene addition to metharylic acid esters and subsequent ester saponification as described in GB-A 1323183.

The examples below serve merely to illustrate the invention and are not to be interpreted in a restrictive manner.

The purities reported were determined by means of gas chromatography (GC) or high performance liquid chromatography (HPLC) via the area ratios of the particular peaks.

In connection with the NMR spectra, s is a singlet, d is a doublet, t is a triplet and q is a quartet. MS stands for mass spectrum and IR for IR spectrum.

Example 1 : Preparation of 2,2-Dichloro-1-methyl-cyclopropanecarbonyl chloride (V)

2,2-Dichloro-1-methyl-cyclopropanecarboxylic acid (1002 g) was charged into a 4 L vessel and dissolved by addition of dichloromethane (1836 g) The solution was warmed up to 40 ⁰ C. Dimethylformamide (0.8 g) was added to the solution.

Thionylchloride (141 1 g) was added over 3 h at 40 ⁰ C. The acidic off-gas was vented through a sodium hydroxide solution. The reaction mixture was kept at 40°C over about 12 h. The solvent was removed at 40 ⁰ C and a final vacuum of 25 mbar. The crude oil was rectified at 10-20 mbar. The fractions between 60 and 74°C were collected. The rectification was repeated at 25 mbar after colorization of the product occurred during storage. The fractions between 77-78°C were collected. A total mass of 771 g of the title compound with a GC purity of 97-98 area% was obtained. This corresponds to a yield of 68 %.

MS (El): 186 m/e (M ⁺ -ion), 151 (M ⁺ - Cl) IR (KBr): 1788 cm- ¹ (C=O) ¹ H-NMR (500 MHz, CDCI ₃ ): δ/ppm = 1.65 (d, 1 H); 1.75 (s, 3H); 2.38 (s, 1 H)

¹³ C-NMR (500 MHz, CDCI ₃ ): δ/ppm = 19.28 (q); 32.41 (t); 43.71 (s); 61.85 (s); 171.18 (S)

Example 2: Preparation of 2,2-Dichloro-1-methyl-cyclopropanecarboxylic-acid ethylamide (IV)

2,2-Dichloro-1-methyl-cyclopropanecarbonyl chloride (25 g) was dosed to pre-charged aqueous ethylamine (24.5 g 70 wt-% solution) at 0 ⁰ C to 10 ⁰ C in a 250 ml vessel. A white precipitate was formed which was dissolved by addition of 80 ml toluene at 50 ⁰ C. The aqueous phase was separated and the toluene was removed by distillation. A total mass of 23.5 g of the title compound was obtained as a white solid. This corresponds to a yield of 95%.

melting point: 101.5 - 103.3°C MS (EI): 195 m/e (M ⁺ -ion)

IR (KBr): 3321 cm- ¹ (N-H), 1641 cm- ¹ (acid amide 1), 1538 cm- ¹ (acid amide 2)

¹ H-NMR (500 MHz, CDCI ₃ ): δ/ppm = 1.18 (t, 3H); 1.38 (d, 1 H); 1.62 (s, 3H); 2.20 (d,

1 H); 3.28 - 3.48 (m, 2H); 6.44 (s broad, 1 H)

¹³ C-NMR (500 MHz, CDCI ₃ ): δ/ppm = 14.75 (q); 19.57 (q); 30.40 (t); 35.14 (t); 36.44 (s); 62.57 (s); 168.16 (s)

Example 3: Preparation of 2,2-Dichloro-N-ethyl-1-methyl-cyclopropanecarboximidoyl chloride (III')

2,2-Dichloro-1-methyl-cyclopropanecarboxylic-acid ethylamide (99.3 g), toluene (500 g) and dimethylformamide (0.5 g) were charged into a 1 L vessel. The mixture was warmed up to 40 ⁰ C and became a solution. Thionylchloride (91.3 g) was added over 30 min at 40 ⁰ C. The solution was heated up to 1 10 ⁰ C (reflux) and kept for 6 h at reflux. The acidic off-gas was vented through a sodium hydroxide solution. The solvent was removed at 50 ⁰ C and a final vacuum of 100 mbar. The concentrated solution was further rectified at 4 mbar. The fractions between 60.4 - 63.4°C were collected. A total mass of 87 g of the title compound with a GC purity of 98 - 99 area% was obtained. This corresponds to a yield of 80 %.

MS (EI): 213 m/e (M ⁺ -ion)

IR (KBr): 1691 cm- ¹ (C=N)

¹ H-NMR (500 MHz, CDCI ₃ ): δ/ppm = 1.17 (t, 3H); 1.52 (d, 1 H); 1.65 (s, 3H); 2.30 (d,

1 H); 3.54 (q, 2H)

¹³ C-NMR (500 MHz, CDCI ₃ ): δ/ppm = 14.20 (q); 19.70 (q); 32.66 (t); 40.25 (s); 47.83 (t); 63.44 (s); 143.42 (s)

Example 4: Preparation of 2,2-Dichloro-N'-(2,6-dichloro-4-trifluoromethylphenyl)-N- ethyl-1-methylcyclopropane-carbohydrazonamide (I')

2,2-Dichloro-4-trifluoromethylphenyl-hydrazine (22.6 g), tri-n-butylamine (20.7 g) and toluene (15.2 g) were charged into a 250 ml vessel. The mixture was heated up to 70 ⁰ C. A solution of 2,2-Dichloro-N-ethyl-1-methyl-cyclopropanecarboximidoyl chloride (20.0 g) in toluene (15.2 g) were added over 2 h at 70 ⁰ C. The reaction mixture was kept at 70°C for 4 h after addition. Then water (20 g) and 1 molar hydrochloric acid (20 g) were added to the reaction mixture. After phase separation the toluene was evaporated at reduced pressure at 50 ⁰ C. The residual oil (46.6 g) was dissolved in isopropanole (80 g) and crystallized by addition of water (80 g). The solid product was dried at 30 ⁰ C / 2 mbar in a vacuum dryer. A total mass of 33.8 g of the title compound with a HPLC purity of 99.9 area-% was obtained a white solid. This corresponds to a yield of 85%.

melting point: 79°C

MS (El): 421 m/e (M ⁺ -ion, isotopic pattern corresponds to 6 Cl atoms)

The ¹ H and ¹³ C NMR spectra of the isolated compound showed two sets of signals, referred to hereinafter as "isomer 1" and "isomer 2".

¹ H-NMR (400 MHz, DMSO-d6): δ/ppm = 1.1 (t, 3H, isomer 1 ); 1.28 (t, 3H, isomer 2);

1.47 (s, 3H, isomer 2); 1.58 (s, 3H, isomer 1 ); 1.6 (d, 1 H, isomer 2); 1.7 (d, 1 H, isomer

1); 2.0 (d, 1 H, isomer 1 ); 2.1 (d, 1 H, isomer 2); 2.9 -3.18 (m, 2H, isomer 1); 3.15 - 3.43 (m, 2H, isomer 2); 6.3 - 6.45 (m, 1 H isomer 1 and 2); 6.95 (s, 1 H, isomer 2); 7.2 (s, 1 H, isomer 1 ); 7.73 (s, 2H, isomer 1 and 2)

¹³ C-NMR (500 MHz, DMSO-d6): δ/ppm = 14.00 (q, isomer 1); 16.07 (q, isomer 2);

18.58 (q, isomer 1); 20.30 (q, isomer 2); 30.19 (t, isomer 2); 30.32 (t, isomer 1 ); 33.15

(s, isomer 2); 33.88 (s, isomer 1 ); 35.97 (t, isomer 1); 37.88 (t, isomer 2); 64.37 (s, isomer 1 ); 65.43 (s, isomer 2); 121.44 (CF3, isomer 1 ); 121.94 (CF3, isomer 2); 124.2 -

126.37 (aromatic ring C-atoms of isomer 1 and 2); 144.14 (s, isomer 1 ); 144.99 (s, isomer 2); 152.87 (s, isomer 2); 156.16 (s, isomer 1)

Example 5: Preparation of 2,2-Dichloro-N'-(2,6-dichloro-4-trifluoromethylphenyl)-N- ethyl-1-methylcyclopropane-carbohydrazonamide (I')

2,2-Dichloro-4-trifluoromethylphenyl-hydrazine (100 g), tri-n-butylamine (76.4 g) and toluene (104.1 g) were charged into a 750 ml vessel. The mixture was heated up to 45°C. 186.3 g of a solution of 48.4 wt-% of 2,2-Dichloro-N-ethyl-1-methyl- cyclopropanecarboximidoyl chloride in toluene were then added over a period of 2 h while keeping the reaction mixture at 45°C. After addition the reaction mixture was kept at 70°C for 1 h. After cooling to 25°C water (190 g) was added and the pH was

adjusted to 4 by addition of sodium hydroxide solution. After phase separation the toluene phase was extracted twice with water (2 x 125g) and then evaporated under reduced pressure at 50 ⁰ C. The residual oil was dissolved in isopropanole (254 g) and crystallized by addition of water (280 g). The solid product was dried at 30 ⁰ C / 2 mbar in a vacuum dryer. A total mass of 158.6 g of the title compound with a HPLC purity of 99.9 area-% was obtained as a white solid. This corresponds to a yield of 92%.

melting point: 79°C

MS (El): 421 m/e (M ⁺ -ion, isotopic pattern corresponds to 6 Cl atoms)

Example 6: Preparation of 2,2-Dichloro-N-ethyl-1-methyl-cyclopropanecarboximidoyl chloride (IN') without isolation of the intermediates

2,2-Dichloro-1-methyl-cyclopropanecarboxylic acid (450 g) was charged into a 4 L vessel as a melt at 80 ⁰ C and dissolved by addition of toluene (1061 g) at 80 ⁰ C. Thionylchloride (412 g) was added over 1 h at 80 ⁰ C. The acidic off-gas was vented through a sodium hydroxide solution. A part of the solvent (approx. 200 g) was stripped off together with the off-gas. The reaction mixture was kept at 80-85°C over 4 h. A part of the solvent (approx. 435 g) was removed by distillation at 1 10°C head temperature. The concentrated solution (approx. 50 wt-% of acid chloride) was dosed during 45 min to pre-charged mixture of aqueous ethylamine (481.5 g of a 70 wt-% solution) and toluene (490 g) at 40°C in a 4 L vessel. Cooling was applied in order to maintain the temperature at 40°C. The reaction mixture was stirred for 1 h after end of the dosage. The phases were separated at 40 ⁰ C. The toluene layer was extracted once with water (250 g) and dried by azeotropic distillation of toluene/water (454 g) at 110 ⁰ C head temperature. The solution (approx. 50 wt-% of acid ethyl amide) was diluted with toluene (1860 g) and kept at 100°C. Dimethylformamide (2.6 g) was added to the solution. Thionylchloride (468 g) was added over 20 min at 100 ⁰ C. The acidic off-gas was vented through a sodium hydroxide solution. After 6 h at 100 ⁰ C additional thionylchloride (38 g) was added. The reaction mixture was kept at 100 ⁰ C for further 8 h. The reaction solution was concentrated by distillation at 110 ⁰ C head temperature to a residual mass of 1184 g. This solution was further concentrated at 50 mbar and then rectified at 4 mbar. The fractions between 65.4 and 68.5°C were collected. A total mass of 429 g of the title compound with a GC purity of 98-99 area% was obtained. This corresponds to a yield of 76 % based on the used acid.

The reaction solution obtained in Example 6 can also be used to prepare 2,2-Dichloro- N'-(2,6-dichloro-4-trifluoromethylphenyl)-N-ethyl-1-methylcy clopropane- carbohydrazonamide (I') according to the procedure described in Example 4 or 5.