AU741658B2

AU741658B2 - Method of producing substituted 2-nitroguanidine derivatives

Info

Publication number: AU741658B2
Application number: AU93442/98A
Authority: AU
Inventors: Peter Maienfisch
Original assignee: Novartis AG
Current assignee: Syngenta Participations AG
Priority date: 1997-08-20
Filing date: 1998-08-18
Publication date: 2001-12-06
Anticipated expiration: 2018-08-18
Also published as: WO1999009009A1; CN1271346A; JP2001515066A; IL134502A0; KR20010023053A; HUP0003632A3; ID24319A; BR9811966A; PL338778A1; HUP0003632A2; EP1005456A1; AU9344298A; CA2301172A1

Description

-1- Method of producing substituted 2-nitroquanidine derivatives The present invention relates to a novel type of method of producing substituted 2-nitroguanidine derivatives.

It is known that, in order to produce 1,3-disubstituted 2-nitroguanidines, a further substituent may be introduced into monosubstituted 2-nitroguanidines 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 by hydrolysis of hexahydro-triazines is described.

It has now been shown that the above-described methods of producing compounds of formula 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, at least one embodiment of the present invention provides 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 ee gold SII.ll e -2-

R

H 1 2 A Y N

N,

NO

2 wherein R, is hydrogen or Cl-C 4 -alkyl;

R

2 is hydrogen, CI-C 6 -alkyl, C 3 -0 6 ,-cycloalkyl or a radical -CH 2

B;

A is 2-chlorothiazole-5-yI; and B is phenyl, 3-pyridyl or thiazolyl, which are optionally substituted by one to three substituents from the group comprising CI-C 3 -alkyl, Cl-C 3 -halogenalkyl, cyclopropyl, ha loge ncyclopropyl, C 2

-C

3 -alkenyl, C 2

-C

3 -alkynyl, C 1

-C

3 -alkoxy, C 2

-C

3 -halogenalkeny!,

C

2

-C

3 -halogenalkynyl, Cl-C 3 -halogenalkoxy, C 1

-C

3 -alkylthio, Cl-C 3 -halogenalkylthio, allyloxy, propargyloxy, allylthio, propargylthio, halogenallyloxy, halogenallylthio, halogen, cyano and nitro; and, if appropriate, the possible E/Z isomers, EIZ isomeric mixtures and/or tautomers thereof, each in free form or in salt form; wherein a compound of formula R2

IN

Ri ,NO 2 V, wherein R 1

R

2 and A have the same significances as given for formula and

R

3 is unsubstituted or substituted C 11

-C

22 -alkyl, C 7 -C1 6 -CYcloalkyl, 0 3

-C

2 0 -alkenyl, C 3

-C

20 o.

alkynyl, N(R 4

)R

5 optionally substituted aryl except for unsubstituted and substituted phenyl; or an optionally substituted, aromatic or non-aromatic, monocyclic or bicyclic, ,:KA4: heterocyclic radical; PI/5-30128/A -3-

R

4 is hydrogen or CI-C 12 -alkyl; Rs is hydrogen, C 1

-C

1 2 -alkyl, C 1

-C

1 2 -alkyl-carbonyl or C 1

-C

1 2 -alkoxy-carbonyl; is hydrolysed.

The compounds of formula may be present as E/Z isomers, e.g. in the following two isomeric forms R2 R2 H H 2 A N N A N NH HY and

HY

Ri N R, ,N

NO

2

O

2

N

Accordingly, any reference to compounds of formula 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 may be present partly in the form of tautomers, for example in the forms H

R

2 H R 2

R

2 H H A N NH A N N A N

NH

I H N and YH R, N R N R 1

HIN

NO

2 H NO 2

NO

Accordingly, any reference to compounds of formula 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 and, where appropriate, the E/Z isomers and tautomers thereof, may be present as salts. Compounds of formula 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 1

-C

4 alkanecarboxylic acids substituted where appropriate for example by halogen, e.g. acetic acid, such as optionally unsaturated dicarboxylic acids, e.g. oxalic, malonic, maleic, 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 1

-C

4 alkanesulfonic or arylsulfonic acids substituted where appropriate for example by halogen, e.g. methanesulfonic or p-toluenesulfonic acid. Salts of compounds of formula with acids of the said kind are preferably obtained when working up the reaction mixtures.

LU

PI/5-30128/A -4- In a broader sense, compounds of formula 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, triethyl or dimethylpropylamine, or a mono-, di- or trihydroxylower 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 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 The same applies to E/Z isomers and tautomers of compounds of formula and salts thereof.

The free form is preferred.

In the definition of formulae 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 alia: 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 CHF 2 or CF 3 ethyl which is mono- to pentasubstituted by fluorine, chlorine and/or bromine, such as CH 2

CF

3

CF

2

CF

3

CF

2 CC13, CF 2 CHC12, CF 2

CHF

2

CF

2 CFCl2, CF 2 CHBr 2

CF

2 CHCIF, CF 2 CHBrF or CCIFCHCIF; propyl or isopropyl, mono- to heptasubstituted by fluorine, chlorine and/or bromine, such as CH 2 CHBrCH 2 Br, CF 2

CHFCF

3

CH

2

CF

2

CF

3 or

CH(CF

3 2 butyl or one of its isomers, mono- to nonasubstituted by fluorine, chlorine and/or PI/5-30128/A bromine, such as CF(CF 3

)CHFCF

3 or CH 2

(CF

2 2

CF

3 2-chlorocyclopropyl or 2,2difluorocyclopropyl; 2,2-difluorovinyl, 2,2-dichlorovinyl, 2-chloroalkyl, 2,3-dichlorovinyl or 2,3dibromovinyl.

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 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 R 3 may be, for example, cyclodecyl, cyclohexadecyl, cyclododecyl or cyclooctadecyl.

Aryl signifies phenyl, naphthyl, phenanthrenyl or anthracenyl, in conjunction with the substituents R 3 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 7membered, 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 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 1200C, preferably 20 to 80 0

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.

PI/5-30128/A -6ethers, 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-C 4 alkanecarboxylic acids substituted where appropriate for example by halogen, e.g. acetic acid, such as optionally unsaturated dicarboxylic acids, e.g. oxalic, malonic, maleic, 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 1

-C

4 alkane- or arylsulfonic acids substituted where appropriate for example by halogen, e.g. methanesulfonic or p-toluenesulfonic acid.

Suitable bases for carrying out the process are preferably hydroxides of alkali metals and alkaline earth metals, such as NaOH and KOH, carbonates such as Na 2

CO

3 NaHCO 3

K

2

CO

3 phosphates such as Na 3

PO

4 Na 2

HPO

4 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 dimethylpropyl-amine, or a mono-, di- or trihydroxy lower alkylamine, e.g. mono-, di- or triethanolamine, 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 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- 2-halogenthiazol-5-yl, tetrahydrofuran-3-yl, 5-methyl-tetrahydrofuran-3yl, 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 1

-C

3 -alkyl, C 1

-C

3 -halogenalkyl and C 1

-C

3 -halogenalkoxy each with 1 to 7 halogen -atoms, and Cl-C 3 -alkoxy.

Furthermore, compounds of formula 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 1

-C

3 -alkyl, Cl-C 3 -halogenalkyl and C 1

-C

3 -halogenalkoxy each with 1 to 7 halogen atoms, and C 1

-C

3 -alkoxy.

Of the compounds of formula to be produced according to the invention, those that are notable are those in which R, is hydrogen, R 2 is hydrogen, methyl, ethyl or cyclopropyl and A is pyridyl, 1-oxopyridyl, tetrahydrofuranyl, thiazolyl, or A is pyridyl, 1-oxopyridinio, tetrahydrofuranyl or thiazolyl which is respectively substituted by one to three substituents from the group halogen, C 1

-C

3 -alkyl, C 1

-C

3 -halogenalkyl and C 1

-C

3 -halogenalkoxy each with 1 to 7 halogen atoms, and C 1 -C-alkoxy. In this context, the preparation of those compounds of formula is of particular interest, in which a) R, is hydrogen; b) R 2 is hydrogen, C 1

-C

3 -alkyl or cyclopropyl, especially methyl; c) A is 2-chloropyrid-5-yl, tetrahydrofuran-3-yl, 2-methyl-tetrahydrofuran-4-yl or 2-chloro- In the compounds of formulae (II) and (111) listed hereinbefore and hereinafter, the substituents for the radical R 3 which may be considered are in particular C 1 1

-C

16 -alkyl;

C

11 -Ce 1 -alkyl substituted by hydroxy or -COO-C 1

-C

16 -alkyl; C 3

-C

18 -alkenyl optionally substituted by phenyl or hydroxy; C 3 -Ce 1 -alkynyl optionally substituted by phenyl; cyclooctyl, cyclodecyl, cycloheptyl, cyclododecyl, thiazolyl, pyridyl, pyridinyl, pyrazinyl or optionally substituted naphthyl.

A further aspect of the invention is b) a method of producing a compound of formula 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

R

3 I R2

N

e

NO

2 wherein R 2 and R 3 are as defined above for formula and optionally the E/Z isomers, E/Z sei c mixtures and/or tautomers thereof, each in free form or in salt form, is reacted with a comp und of formula

>AT

-8- YYT

(IV),

R1 which is known or may be produced analogously to methods known per se, wherein R 1 and A are defined as given above for formula and Y is a leaving group, preferably halogen, preferably in the presence of a base.

A further aspect 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

I 2 R2N NH2 0 2

/N

which is known or may be produced analogously to methods known per se, and wherein R 2 has the same significance as defined for formula is reacted with a compound of formula

H

2

N-R

3

(VI),

wherein R 3 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 oo:: presence of an excess of formaldehyde or paraformaldehyde.

A further aspect of the invention is o d) a method of producing a compound of formula 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 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 and this compound of formula (II) is hydrolysed.

A further aspect of the invention is e) the use of the compounds of formula (II) in the preparation of the compounds of formula Preferred embodiments of the method according to variants b) to d) may be taken from the R-ADxamples.

-9- 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.

The compounds of formula 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 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

N N-n-C18H37 ON N-

H

3

C

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 0 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 N CH 2 N02N N- H3C frSt ire of 3.54 g of 1-methyl-2-nitroguanidine, 2.7 ml of allylamine, 50 ml of toluene and 2.7 g of araformaldehyde is mixed with 3 drops of concentrated hydrochloric acid and PI/5-30128/A heated for 20 hours on a water separator. Then, the mixture is evaporated to dryness under vacuum, the residue taken up with dichloromethane/methanol (98:29, 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--

k ON N

H

3

C

A mixture of 5.9 g of 1-methyl-2-nitroguanidine, 5.2 g of 3-aminopyridine, 4.5 g of paraformaldehyde, 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 0 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

R

rN) H N. CH3 (Ilia)

N

NO

2 No. R 3 phys. data 1.1 cyclooctyl 1.2 cyclodecyl 1.3 cycloheptyl 1.4 -(CH2)o-CH3

-(CH

2 11

-CH

3 m.p. 85-87 °C 1.6

-(CH

2 12

-CH

3 1.7

-(CH

2 1 3

-CH

3 1.8

-(CH

2 14

-CH

3 P /5-301 28/A -11 No. R 3 phys. data 1.9 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20

-(CH

2 15

-CH

3

-(CH

2 17

-CH

3

-(CH

2 8

-CH=CH-(CH

2 7

-CH

3 (cis)

-(CH

2 )lo-COOH

-(CH

2 1 1

-COOH

-CH

2

-CH=CH

2

-CH-(CH

2

QH)CH(OH)-CH=CH-(CH

2 12

-CH

3

-CH

2

-CH=CH(CH

3

)-(CH

2 2

-CH=C(CH

3 2

-CH-(CH

2

OH)CH(OH)-C=-C-(CH

2 12

-CH

3

-(CH

2 3

-C=C-C

6

H

-C H 2

-C-=C-C

6

H

m. p. 93-95 TC m.p. 53-55 0

C

1.21 1.22 1.23 1.24 1.25 1.26 1.27 1.28 1.29 1.30 1.31 1.32 naht-1 naphth-1 -yI thiazol-2-yI pyrid-3-yI pyrid-4-yI 3-bromonaphth-2-yi 1 -hydroxy-naphth-2-yI 4-methoxy-naphth-2-yi 5-hydroxy-naphth-2-yl 1 -chloronaphth-2-yi m.p. 204-208 0

C

r PI/5-30128/A No.

-12phys. data 1.33 1.34 1.35 1.36 1.37 1.38 1.39 8-nitronapht-2-yl

-NHCOOC

2

H

5

O

0 0

NH

cyclododecyl 0 N O C H S

-CH

2 1 1 -C(=0)OCH 3 m.p. 203-204 °C m.p. 156-158 °C m.p. 137-139 °C m.p. 56-57 °C m.p. 91-94 °C Example P2.1: Preparation of the compound of formula A mixture of 6.0 g of the compound obtainable according to example P1.1, 2.8 g of 2-chloroand 4.8 g of potassium carbonate in 20 ml of dimethylformamide is stirred for 10 hours at 50 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 0 C (compound 10.B.1).

The following compounds of formula (II) listed in Tables 2 to 13 can also be obtained -a~Qalogously to the above method of example P2.1.

P1/5-30128/A -13- Table A Compounds of formula

R

rN, y y NCH 3 H N, (I Ia), No.

R

NO

2 No. [R 3 A. 1 A.2 A.3 AA4 A.6 A.7 A.8 A.9 Al1 A. 12 A.13 A. 14 A.16 A.17 A.18 A.19 cyctooctyl cyclodlecyl cycloheptyl

-(CH

2 10

-CH

3

-(CH

2 1 1

-CH

3

-(CH

2 12

-CH

3

-(CH

2 13

-CH

3

-(CH

2 14

-CH

3

-(CH

2 15

-CH

3

-(CH

2 8

-CH=CH-(CH

2 7

-CH

3 (cis)

-(CH

2 )lo-COOH

-(CH

2 11

-COOH

-CH

2

-CH=CH

2

-CH-(CH

2

OH)CH(OH)-CH=CH-

(CH

2 12

-CH

3

-CH

2

-CH=CH(CH

3

)-(CH

2 2

CH=C(CH

3 2

-CH-(CH

2

OH)CH(OH)-C=-C-

(CH

2 12

-CH

3

-(CH

2 3

-C=C-C

6

H

5

-CH

2

-C=C-C

6

H

5 A.21 A.22 A.23 A.24 A.25 A.26 A.27 A.28 A.29 A.30 A.31 A.32 A.33 A.34 ht--yl naphth-1 -yl thiazol-2-yl pyrid-3-yl pyrid-4-yl 3-b ro mo na phth-2-yl 1 -hydroxy-naphth-2-yl 4-methoxy-naphth-2-yl 5-hydroxy-naphth-2-yl 1 -chloronaphth-2-yl 8-nitro-naphth-2-yl

-NHCOOC

2

H

PI/5-30128/A -14- No.

R

3 R3

O

0 No.

R

3 A.38 0 A 9O (CH321- CIL S A.39 -CH 2 11

-C(=O)OCH

3 A.36 A.37 cyclododecyl Table 2: Compounds of the general formula wherein A signifies C

N

R

3 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 corresponds in each case to one line of Table A.

Y

and and R 3 Table 4: Compounds of the general formula (Ila), wherein A signifies

N_

R

3 corresponds in each case to one line of Table A.

Table 5: Compounds of the general formula wherein A signifies H Scorresponds in each case to one line of Table A.

R

3 corresponds in each case to one line of Table A.

and and P1/5-30128/A Table 6: Compounds of the general formula (lla), wherein A signifies Ha 3 "and

O._

R

3 corresponds in each case to one line of Table A.

Table 7: Compounds of the general formula (Ila), wherein A signifies and R 3 corresponds in each case to one line of Table A.

Table 8: Compounds of the general formula (Ila), wherein A signifies and

N-O

R

3 corresponds in each case to one line of Table A.

Table 9: Compounds of the general formula (lla), wherein A signifies C and

N

R

3 corresponds in each case to one line of Table A.

Compound 9.A.10: m.p. 95-97°C.

Compound 9.A.14: m.p. 75-77°C.

Compound 9.A.26: m.p. 222°C.

Compound 9.A.34: m.p. 200°C.

Compound 9.A.35: m.p. 178-180 *C.

Compound 9.A.36: m.p. 214 OC.

Table 10: Compounds of the general formula (Ila), wherein A signifies and R 3 corresponds in each case to one line of Table A.

Table 11: Compounds of the general formula (lla), wherein A signifies N+ and R 3 rresponds in each case to one line of Table A.

-corresponds in each case to one line of Table A.

PI/5-30128/A -16- Table 12: Compounds of the general formula (lla), wherein A signifies Cl N+ and I 0

R

3 corresponds in each case to one line of Table A.

CIand Table 13: Compounds of the general formula (Ila), wherein A signifies and CI N

R

3 corresponds in each case to one line of Table A.

Example 3.1: Preparation of the compound of formula Cl H H

SN

NO

2 g of the compound obtainable according to example P2.1 are stirred for 16 hours at 50 0

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 listed in Table 14 can also be obtained analogously to the above method of example P3.1.

Table 14: Compounds of the general formula H3C N-H

(I)

0 2 N

/N

H

A

P1/5-30 128/A -17- No. A Phys.data 14.1 14.2 14.3 14.4 14.5 14.6 14.7

CI

N

H

3 C s

N

m.p. 147-149 0

C

14.8 14.9 14.10 Ci) N

N

H

3 C 0 N-0 14.11 -18- No. A Phys.data 14.12

N+

I

O

A further aspect 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 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.

Throughout this specification and the claims which follow, unless the context requires otherwise, the word "comprise", and variations such as "comprises" and "comprising", will be understood to imply the inclusion of a stated integer or step or group of integers or steps but not the exclusion of any other integer or step or group of integers or steps.

The reference to any prior art in this specification is not, and should not be taken as, an acknowledgment or any form of suggestion that that prior art forms part of the common general knowledge in Australia.

o*o• o °o: oo• ••ooo

Claims

1. Method of producing a compound of formula H 1 A i N N NO 2 wherein R, is hydrogen or 0 1 -C 4 -alkyl; R 2 is hydrogen, Cl-C 6 -alkyl, C 3 -C 6 -cycloalkyl or a radical -CH 2 B; A is 2-chlorothiazole-5-yl; and B is phenyl, 3-pyridyl or thiazolyl, which are optionally substituted by one to three substituents from the group comprising Cl-C 3 -alkyl, C 1 -C 3 -halogenalkyl, cyclopropyl, :halogencyclopropyl, C 2 -0 3 -alkenyl, C 2 -C 3 -alkynyl, Cl-C 3 -alkoxy, C 2 -C 3 -halogenalkenyl, C 2 -C 3 -halogenalkynyl, Cl-C 3 -halogenalkoxy, Cl-0 3 -alkylthio, Cl-C 3 -halogenalkylthio, allyloxy, propargyloxy, allylthio, propargylthio, halogenallyloxy, halogen allylthio, halogen, cyano and nitro; and, if appropriate, the possible EIZ isomers, EIZ isomeric mixtures and/or tautomers thereof, each in free form or in salt form; wherein a compound of formula *Y NN I N 0 wherein R 1 R 2 and A have the same significances as given for formula and R is unsubstituted or substituted C 11 -C 22 -alkyl, C 7 -0 16 -cycloalkyl, C 3 -C 20 -alkenyl, C 3 -0 20 ST"Npyyl N(R4)R 5 optionally substituted aryl except for unsubstituted and substituted phenyl; or an optionally substituted, aromatic or non-aromatic, monocyclic or bicyclic, heterocyclic radical; R 4 is hydrogen or C 1 -C 12 -alkyl; Rs is hydrogen, C 1 -C 12 -alkyl, C 1 -C 12 -alkyl-carbonyl or CI-C 1 2 -alkoxy-carbonyl, is hydrolysed.

2. Method according to claim 1 of producing a compound of formula in free form.

3. Method according to one of claims 1 or 2 of producing a compound of formula wherein R, is hydrogen.

4. Method according to any one of claims 1 to 3 of producing a compound of formula wherein R 2 is hydrogen, Cl-C 3 -alkyl or cyclopropyl. Method according to any one of claims 1 to 4 of producing a compound of formula from a compound of formula wherein R 3 is C 11 -C 16 -alkyl; C 11 -C1 8 -alkyl substituted by hydroxy or -COO-Cl-Cia-alkyl; C 3 -C 18 -alkenyl optionally substituted by phenyl or hydroxy; C 3 -C 1 8 -alkynyl optionally substituted by phenyl; cyclooctyl, cyclodecyl, cycloheptyl, cyclododecyl, thiazolyl, pyridyl, pyridinyl, pyrazinyl or optionally substituted naphthyl.

6. Method according to any one of claims 1 to 5 of producing a compound of formula wherein the pH value lies between 7 and 12. 9

7. Method according to any one of claims 1 to 5 of producing a compound of formula wherein the pH value lies between 5 and 1.

8. A method of producing a compound of formula (II) as defined in claim 1, and optionally the E/Z isomers, E/Z isomeric mixtures and/or tautomers thereof, each in free form or in salt form, wherein a compound of formula o -21 R 3 N (111), H R2 N, NO 2 wherein R 2 and R 3 are as defined above in claim 1 for formula 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 1 wherein R 1 and A are defined as in claim 1 for formula and Y is a leaving group.

9. A method of producing a compound of formula III as defined in claim 8, and optionally the E/Z isomers, E/Z isomeric mixtures and/or tautomers thereof, each in free form or in salt form, wherein a compound of formula H N NH N 0 2 N wherein R 2 has the same significance as defined in claim 1 for formula is reacted with a compound of formula S H 2 N-R 3 (VI), wherein R 3 has the same significance as defined in claim 1 for the compounds of formula in the presence of an excess of formaldehyde or paraformaldehyde. •l• tol fA A.. A A oo P:\OPER\Kbm\93442-98 rs .doc-12/09/01 -22- A method of preparing a compound of formula according to claim 1, substantially as hereinbefore described with reference to the Examples.

11. A method of preparing a compound of formula (II) according to claim 8, substantially as hereinbefore described with reference to the Examples.

12. A method of preparing a compound of formula (III) according to claim 9, substantially as hereinbefore described with reference to the Examples.

13. A compound of formula as defined in claim 1, prepared by the method of claim 1 or claim

14. A compound of formula as defined in claim 1, prepared by the method of claim 8 or claim 11. A compound of formula (III), as defined in claim 8, prepared by the method of claim 9 or claim 12. DATED this 12th day of September, 2001 Novartis AG By DAVIES COLLISON CAVE Patent Attorneys for the applicant