AU617513B2

AU617513B2 - Substituted pyridines, processes for their preparation, and their use as insecticides

Info

Publication number: AU617513B2
Application number: AU40252/89A
Authority: AU
Inventors: Bernd Alig; Michael Londershausen; Wilhelm Stendel
Original assignee: Bayer AG
Current assignee: Bayer AG
Priority date: 1988-08-25
Filing date: 1989-08-24
Publication date: 1991-11-28
Anticipated expiration: 2009-08-24
Also published as: NZ230381A; ZA896454B; DE3828820A1; EP0356797A3; AU4025289A; JPH02117660A; DK418689D0; KR900003126A; EP0356797A2; IL91384A0; DK418689A; BR8904250A

Description

hwntor(s).

Attmtation or Iqazliosi not Nqulmd.

To: application(s) made in a Convention country in respect of the invention the subject of the application.

Declared at Leverkusen this 13th Le A 26 281-AU 'The Commissioner of Patents ARTHUR S. CAVE CO.

day f July 1989 rrrsin.,S1-~11 2TU~2? ~1~ Our Ref: 285674

AUSTRALIA

Patents Act FORM COMPLETE SPECIFICATION

(ORIGINAL)

6~7513 Application Number: Lodged: Complete Specification Lodged: Accepted: Published: Priority: Related Art: Applicant(s): 4 t i Bayer Aktiengesellschaft

LEVERKUSEN

FEDERAL REPUBLIC OF GERMANY ARTHUR S. CAVE CO.

Patent Trade Mark Attornerys Level 10, 10 Barrack Street SYDNEY NSW 2000 Address for Service: Complete specificati

I

on for the invention entitled "Substituted pyridines, processes for their preparation, and their use as insecticides".

The following statement is a full description of this invention, including the best method of performing it known to me:- 1 5020 A The present invention relates to substituted pyridines, processes for their preparation, intermediates for this, and their use as insecticides.

r 5 1. The novel substituted pyridines of the formula I have been found £tt R3 R4

I

a410 in which 0000 X represents 0, S, NH, -CH 2

-CHCH

3 15 -C(CH3)2- *0 Y represents straight-chain or branched aLkylene which is optionally interrupted by oxygen, RI represents identical or different radicals from the group comprising hydrogen, haLogen, alkyL, alkoxy, halogenoalkyl, R2 represents identical or different radicaLs from the group comprising hydrogen, halogen, alkyl, alkenyl, halogenoalkyl, alkoxy, alkylthio, halogenoaLkoxy, halogenoalkylthio, Le A 26 281 lai R represents hydrogen, alkyl, halogenoalkyl, alkoxyalkyl, alkenoxyalkyl, alkenyl, alkinyl, 4 3 R represents the radicals indicated for R R and R together can represent a direct bond, R represents hydrogen, halogen, alkyl, halogenoalkyL, alkoxy, amino, aikylureido, alkylamino, dialkylamino, phenylureido, substituted phenylureido, morpholinyl, dimethylmorpholinyl, piperazinyl, N-alkylpiperazinyl, and their salts with acids.

2. Processes have been found for the preparation of S. the substituted pyridines of the formula I, which are characterized in that a) compounds of the formula II r.

R

3

R

4 R I X -CH ,CH-OH II .x Y in which

R

1

R

2

R

3

R

4 X, Y have the abovementioned meaning are reacted with halogenopyridines of the formula III Le A 26 281 2

I

in which Hal represents halogen and R 5has the abovementioned meaning, or b) compounds of the formula IV

R

3 R4 R a X4> -C y CH-H4al I V in which R R R R, X, Y have the abovementioned meaning and HaL represents halogen '~are reacted with hydroxypyridlines of the formula V;in which R5has the' abovementioned meaning.

Le A 26 281 3- HL-0H>

R

3

R

4

RI

-CH, YH-OH

II

in which R R R, R X, Y have the abovementioned meaning are novel.

4. They are prepared by reacting compounds of the for- H mula VI I 'R 2 in which '11 2 R R X have the abovementioned meaning with compounds of the formulae VII or VIII

R

3

R

4 I I VII

CH--CH

in which Le A 26 281 4

I

R and R have the abovementioned meaning

R

3

R

4 I I Hal-CH CH-OH

VIII

in which 3 4 Hal, R R Y have the abovementioned meaning.

The compounds of the formula I and their salts with acids are suitable for controLLing insects. Particularly preferably, they can be employed for controlling fleas, in particular against Pulex irritans, Xenopsylla cheopis, Ctenocephalides canis, Ctenocephalides felis, Ceratophyllus gallinae, Echidnophaga gallinacea, Tunga penetrans.

The compounds of the formula I possess properties which S* inhibit the development of insects. They can thus be employed against all or individual developmental stages of insects, in particular of fleas.

Preferred compounds of the formula I are those in which X represents O, S, CH 2 Y represents straight-chain or branched alkylene which has up to 12 C atoms and which is optionally interrupted by 1 to 6 oxygen atoms.

R

1 represents identical or different radicals from Le A 26 281 5 .the group comprising hydrogen, halogen such as chLorine, R 2 represents identical or different radicals from the group comprising hydrogen, chLorine, bromine,

C

1 4 -aLkyL such as methyl, ethyl, i-propyL, tbutyl, C 2 4 -aLkenyL such as aLLyL, Cl.

4 -haLogenoalkyl such as trifLuoromethyL, Cl.

4 -aLkoxy, C 1 4 haLogenoalkoxy such as trifLuoromethoxy, R 3represents hydrogen, Cl 1 4 -aLkyL such as methyl, R 4represents hydrogen, C 1 4 -aLkyL such as methyl, 15 ethyl, propyL, butyL, C.-haLogenoaLkyL such as trifLuoromethyL, Cl.

4 -aLkoxy-Cl.

4 -aLkyL such as methoxymethyL, n- or t-butoxymethyL, i-propoxymethyL,

C

2 4 -aLkenyL such as aLLyL, C 2 4 -aLkenoxy-Cl 1 4 aLkyL such as aLkyLoxymethyL, R and Rtogether represent a direct bond and together with the adjacent C atoms and Y can represent cycLopentyL or cycLohexyL, R 5 represents halogen such as chlorine, bromine, C 1 4 aLkyL such as methyl, ethyl, Cl 1 4 -haLogenoaLkyL such as trifLuoromethyL, aLkoxy such as methoxy, amino, alkylureido, phenylureido, substituted phenyLureido, morphoL inyL, dliiethyLmorphoL inyL, piperazinyL, N-aLkyLpiperazinyL.

Le A 26 281 6 Particularly preferred compounds of the formula I are those in which X represents 0, Y represents alkyLene which has up tc 5 C atoms and which is optionally interrupted by 0, such as, for example, methylene -CH 2 -0-CH 2

-CH

2 -0-CH 2 -0-CH 2

-CH(CH

3 )-0-CH 2 R represents hydrogen, 2 S R represents hydrogen, halogen, in particular chLorine or bromine, C 1 4 -alky, C 2 4 -alkenyl, in particular alkyl, d3 o R represents hydrogen, methyl, ethyl, propyl, butyl, C 2 4 -alkeny, in particular allyl, C 1 4 -alkoxy-C 1 4 -alkyl, in particular methoxy-, ethoxy-, isopropoxy-, butoxytmethyl, C 2 4 -aLkenoxy-C 1 4 -aLkyL, in particular allyloxymethyL, 3 4 R and R represent a direct bond and together with the adjacent C atoms and Y represent cyclopentyl or cyclohexyL,

R

5 represents C 1 4 -alkyL, C 1 .4-alkoxy, in particular Le A 26 281 7 methoxy, Cl- 4 -haLogenoaLkyL, in particular trifLuorom~thyL, amino, halogen, in particular chlorine, Cl- 4 -aLkyLureido, in particular methylureido, phenyLureido, it being possible for the phenyL ring to be optionally substituted by halogen, aLkyL, aLkoxy, haLogenoaLkyL, haLogenoaLkoxy.

The following may be mentioned individually: 3 4 6 4 444 $444 4 4444 0 1,3 C1 2 4,4.

4 4 4 44 4

II

4 4 4 4 44 4 44 4 4 4 44

-CH

2

-CH

2 -0-CH 2

-CH-

C;M

3

CH

3

-CH'

2

-CH-O-CH

2

-CH-

U11 3

-CH

2

-CH

2 -0-CH 2

CH

2

-CH

2

-CH

2 -0-CH 2

CH

2 3-NH 2 5-N 0 4-NH 2 3-OCH 3 0 113-C1 2 0 1,3-Cl 2 Le A 26 281-8 8 s 1,3-Cl 2 0 3-Br

-CH

2

-CH

2 -0-CH 2

CH

2 5-OCH 3

-CH

2

-CH

2 -0-CH 2

CH

2 5-OCH 3 4 4,4 4 00 0 04 00 0 06 Le A 26 281- 9 U *4, .m ~'~At

CH

2 1,3-Cl 2

-CH

2 -CH-OCHZCHZ-OCH2CH2- 3-NH 2

CH

2 H

-CH

2

-CH

2

-O-CH

2 1 CH 5-CF 3

CH

3 0 H

-CH

2 -CH-0-CH 2

CH-

CHk 3

CF

3

-CH

2 -CH-0CH 2

CH

2

CI

2

CH

3 5-N 0

CH

3 5-N N-CH 3 44:15 4 4 4f 4f t S H 0 1,3-Cl 2

-CHZ-CH

2 0CH 2

CH

2 3-HCNHO 0 CH4 3 0 1,3-C1 2

-CH

2 -CH-0-CH2

CH

2

CM

3 5-N 0

CM

3

CH

3 5-N 0

CH

3 S 1,3-C1 2

CH

3 -Cn 2 -C-OCHZ 2

CH

2

CH

3 Le A 26 281 10 f -S X R B'

R

CH

3

-CH

2

-CH-O-CH

2

CH

2 CM 2 1,3-Cl 2

CH

3 5-N 0

CM

3 0

CM

3

-CH

2

-CH

2 -0-CH 2

CH

2 5-N 0

CM

3 414e 15 4 4 4 4 *6

I

I 4 4 I 44 0 1,3-Cl 2

-CH

2

CM

2

O-CH

2

-CH

2

CH

3

-CH

2

CH

2 -0-CM 2

CH

2 N r 3-NM-C-NM- 4-OCH 3 0

II

4444 44 I 4 II I 44 0 H 0 H -CH 2 cM 2 -0-CM 2

CM

2

CM

2 4 NM C N- 11 0 Le A 26 281 11 i:; I If, in process 2a for the preparation of the compounds according to the invention, 2-E2-(4'-phenoxyphenoxy)ethoxy3-ethanoL is employed as compound of the formula II and 3-chloropyridine as compound of the formula III, the course of the reaction may be specified by the following S equation: ct r P I 1 1 ,,2

CI

44p 44b 0-CH 2 CH2-0-(CH -OH Cl cOi. IO0-CH2-CH 2 -CH2CH2-0'1 Compounds of the formulae II and III which are preferably employed are those in which R R R R R X, Y have the preferred or particularly preferred meanings indicated for the compounds of the formula I.

The following compounds of the formula II may be mentioned individually: Le A 26 281 12

I-~

4 m

U

I

H

7-Cl 7-Cl 7-Cl

H

CH

2 0 0

S

0 0

CH-CH

3 0 0 s 7-Cl 7-Cl 000 0 0 7-Cl 1-Cl 3-0-CH 2

-CH

2

-O-CH

2

CH

2

-OH

H2-0-CH?-CH2-O-CH C2-OH H 2-0-CH 2

-CH

2 -0-CH 2

CH

2 -0-CH 2

CH

2

-OH

H 2-0-CH 2

-CH

2 -0-CH 2

CH

2

-OH

3-OCH 3 2-0-CH 2 -CH-0--CH 2

-CH-OH

I I CH4 3 CHk 3 3-OCH 3 2-0-CH 2 -CH-0-CH 2

-CH

2

-OH

CF

3 H 2-0-CH 2

-CH

2

-O-CH

2

CH

2

-OH

H 2-0-CH 2

-CH-Q-CH

2

CH

2

-OH

CH

2

F

H 3-0-CH 2 -CH-0-CH 2

CH

2

-OH

CH

2

F

3-OCH 3 2-O-CH 2 -CH-0-CH 2

CH

2

-OH

CH

2

F

H 3-0-CH 2 -CH-0-CH 2

CH

2

-OH

CH

2

-OCF

3 H 2-0-CH 2 -CH-0-CH 2

CH

2

-OH

CH

2

-OCF

3 ,3-t-butyL 2-0-CH-CH 2 -0-CH 2

-CH-OH

I I

-CH

3 U11 3 4444 4444 11 4 I 4 o 14 7-Cl 0 7-Cl s 0 1-Cl Le A 26 281 13 -1- 5020 The following compounds of the formula III may be mentioned individually: 2-chloropyridine, 2-bromopyridine, 3-chloropyridine, 3-bromopyridine, methylpyridine, 2-bromo-5-methylpyridine, 4-chloropyridine, 2-chloro-6-methylpyridine, 2,3-dichloropyridine, 2,6-dichioropyridine, 2,6-dibromo- 2 pyridine, 3,5-dichoropyridine, 2,6-difluoropyridine.

t The compounds of the formula II are novel, their preparation is described further below. The compounds of the formula III are known.

The reaction is carried out by heating the compounds II and III in the presence of diluents, bases and, if appropriate, catalysts.

Son S 0 The reaction is carried out at temperatures from 0 2000C, preferably at 20 100 C, particularly preferably at the 0 a boiling point of the diluent.

Suitable diluents are all inert organic solvents. These 060 preferably include aliphatic and aromatic, optionally a 0, halogenated hydrocarbons, such as pentane, hexane, heptane, cyclohexane, petroleum ether, benzine, ligroin, S 25 benzene, toluene, methylene chloride, ethylene chloride, carbon tetrachloride, chlorobenzene and o-dichLorobenzene, furthermore ethers, such as diethyl ether and dibutyL ether, glycol dimethyl ether and diglycoL dimethyl ether, tetrahydrofuran and dioxane, furthermore ketones, such as acetone,. methyl ethy' ketone, methyl isopropyl ketone and Le A 26 281 14 i i~ il 4 methyl isobutyl ketone, additionally esters, such as methyl acetate and'ethyl acetate, furthermore nitriles, such as, for example, acetonitrile and propionitrile, benzonitrie, glutarodinitrile, furthermore amides, such as, for example, dimethylformamide, dimethylacetamie and N-methylpyrrolidofe, and also dimethyl suiphoxide, tetramethylene suLphone and hexamethylphosphoric triamide.

Suitable bases are inorganic and organic bases. Bases which may be mentioned are the hydroxides, carbonates hydrogen carbonates and alkoxides of alkali metals and alkaline earth metals, furthermore amines, such as, in particular, tertiary amines, for example trimethylaine, triethylamine, N-methylmorpholine, pyridine, picoLines, 44 15 N-ethylpyrrolidine, diazabicyclo(4,3,0)-undecane

CDBU),

1,4-diazabicycLo(2,2,2)octane (DABCO), diazabicyclo- (3,2,0)-nonene (DBN).

(1 Examples of suitable catalysts are phase transfer catalysts, such as tris-C2-(2-methoxyethoxy)]-ethyL-amine (TDA-1), benzyltriethylammonium chloride (TEBA), 1,4,7,10, 13,16-hexaoxacycLooctadecane (18-crown-6), tetrabutylammonium bromide, tetrabutylammonium hydrogen sulphate, tetrabutylammonium iodide, methyltrialkyl (C 8

-C

1 0 ammonium chloride (Adogen 464).

The compounds of the formulae II and III are employed in an approximately equimoLar ratio. An excess of one or the other component does not convey any considerable advantages.

Le A 26 281 15 4 L L3 :_I P.- T A- I When the reaction is complete, the diluent is distilled off, and the compounds of the formula I are isolated in a manner known per se, for example by extracting them from the residue, choosing a suitable solvent, for example ether. The compounds of the formula I can subsequently be purified in a customary manner, for example by distilling.

If, in process 2b for the preparation of the compounds of the formula I, 3-chloropropyloxy-diphenyl ether is employed as compound of the formula IV and 4-hydroxy-3amino-pyridine as compound of the formula V, the course of the reaction can be represented by the following equation: 4 4 .4 4'( 4 4 44 444 4.44 4. 1 0 1' (CH2) 3-Cl H

NH

2 NH2 20 NH2 The process is preferably employed when the compound of the formula V contains an amino group.

Compounds of the formulae IV and V which are preferably employed are those in which R 1

R

2

R

3 R R 5 X, Y have the preferred or particularly preferred meanings indicated Le A 26 281 16 for the compounds of the formula

I.

The following compounds of the formula IV may be mentioned indlividlually:

R

1 x R2M H

CH

2 1-Cl 3 O-CH 2

-CH

2 -Cl 7-Cl 0 H 2-0-CH 2

CH

2 -Cl H S H 3-0-CH 2

CH

2 -Cl fi* 15 7-Cl 0 H 2-0-CH 2

CH

2

CH

2 -Cl If4. 2- i l 47-Cl 0H *460 404 0* 0 0 00 O 40 7-Cl 0 3-001l 2 0-1: 7 5C 1 2 0%it:7$C 1

CH

2 Le A 26 281 -1 17 Le A 26 281- 4 Rl x RZ m t I 7-Cl 0 7-Cl 0 H 2-0-CH2CH2CH2-Br H 2-0-CH2-CH-Cl

I

CH3 H 2-0-CH2-CH-Cl

I

CH3 H 2-0-CH2-CH-Cl

I

H 2-0-CH2CH2-0-CH2CH2-Cl H 2-0-CH2CH2-0-CH2CH2-OCH2CH2-Cl Le A 26 281 18 The following compounds of the formula V may be mentioned individually: 2-hydroxypyridine, 2-mercaptopyridine, 2hydroxypyrimidine, 3-hydroxypyridine, 2-amino-3-hydroxypyridine, 2-chloro-3-hydroxypyridine, 2,3-di-hydroxypyridine.

The compounds of the formula IV are novel, their preparation is described further below. The compounds of the formula V are known.

The reaction is carried out by heating the compounds IV and V in the presence of diluents, bases and if appropriate catalysts.

The reaction is carried out at temperatures from 0 200 0

C,

o preferably at 20 100°C, particularly preferably at the boiling point of the diluent.

Suitable diluents are all inert organic solvents. These preferably include aLiphatic and aromatic, optionally halogenated hydrocarbons, such as pentane, hexane, heptane, cyclohexane, petroleum ether, benzine, Ligroin, 2 benzene, toluene, methylene chloride, ethylene chloride, carbon tetrachLoride, chlorobenzene and o-dichlorobenzene, furthermore ethers, such as diethyl ether and dibutyl ether, glycol dimethyl ether and diglycol dimethyl ether, tetrahydrofuran and dioxane, furthermore ketones, such as acetone, methyl ethyl ketone, methyl isopropyl ketone and methyl isobutyl ketone, additionally esters, such as methyl acetate and ethyl acetate, furthermore nitriles, Le A 26 281 19 such as, for example, acetonitrile and propionitrie, benzonitrile, glutarodinitrile, furthermore amides, such as, for example, dimethylformamide, dimethylacetamide and N-methyLpyrroLidone, and also dimethyl suLphoxide, tetramethyene suLphone and hexamethyLphosphoric triamide.

Suitable bases are inorganic and organic bases. Bases which may be mentioned are the hydroxides, carbonates hydrogen carbonates and alkoxides of alkali metals and alkaline earth metals, furthermore amines, such as, in particular, tertiary amines, for example trimethyamine, triethylamine, N-methylmorpholine, pyridine, picolines, N-ethylpyrrolidine, diazabicyclo(4,3,0)-undecane (DBU), 1,4-diazabicyclo(2,2,2)octane (DABCO), diazabicyclo- S 15 (3,2,0)-nonene (DBN).

SExamples of suitable catalysts are phase transfer catalysts, such as methyltrialkyL (Cg-C 10 )-ammonium chloride (Adogen 464), 1,4,7,10,13,16-hexaoxacycooctadecane (18-crown-6), tetrabutylammonium bromide, tris-C2-(2methoxyethoxy)-ethyl3-amine (TDA-1), benzyltriethylammonium chloride (TEBA).

The compounds of the formulae IV and V are employed in an approximately equimolar ratio. An excess of one or the other component does not convey any considerable advantages.

When the reaction is complete, the diluent is distilled off, and the compounds-of the formula I are isolated in a Le A 26 281 20 l*ll II I I *r manner known per se, for example by extracting them from the residue, choosing a suitable solvent, for example ether. The compounds of the formula I can subsequently be purified in a customary manner, for example by distil- 5 ling.

tr If, in process 4 for the preparation of the compounds of the formula II, 3-hydroxy-diphenyl ether is employed as CA .compound of the formula VI and propylene oxide as compound of the formula VII, the course of the reaction may be represented by the following equation:

CH

3 S° 2 CH -CH n ,H 0

CH

3

CH

3

-CH

2

-CH-O-CH

2

-CH-OH

Compounds of the formulae VI and VII which are preferably employed are those in which R R R R X, Y have the preferred meanings indicated for the compounds of the formula I.

The following compounds of the formula VI may be mentioned individually: 2-hydroxy-diphenyl ether, 3-hydroxy-diphenyl ether, 4-hydroxy-diphenyl ether, 2-hydroxy-diphenylmethane, Le A 26 281 21 3-hydroxy-di phenylmethane, 4-hydroxy-diphenyLmethane, 3'-trifl:uoromethyLV4-hydroxy-diphelyLmethae, 3'-'trifLuoromethyL-4-hydroxy-diphenyt ether, 4' -ftuoro-4-hydroxydiphenyl ether, 4'-chLoro-4-hydroxy-diphenyL ether, 4'chLoro-3-hydroxy-dophelyL ether, 4'-methoxy-4-hydroxydliphenyl ether, 4'-chLoro-3'-trifLuoromethyL-4-hydroxydliphenyL ether, 4-hydroxy-diphenyLamine, 4'-methyL-4hydroxy-dipheniyl ether, 4-hydroxy-diphenyL suLphidle, 4- C2-phenyL-2-propyL)-phenoL.

following compounds of the formula VII may be mentindindlividually: ij 4 propyLene oxide, 1-chLoro-2,3-epoxypropane, 1-fLuoro-2,3ethoxypropane, 3,3,3-trifLuoro-1,2-epoxypropane, butyL 2,3-epoxypropyL ether, 2,3-epoxypropyL isopropyL ether, aLLyL glycidyL ether, 1-bromo-2,3-epoxypropane, 1,3- Aj 4 butadliene monoxide, cycLopentene oxide, cycLohexene oxide, j cycLoheptene oxide, 1,2-hexene oxide, 1,2-decene oxide, 1,2-dodlecene oxide, 1,2-hexadecene oxide, ,-iehL1 methoxyethyLene oxide, 1,2-epoxy-3--methoxypropane, hexadliene monoxide, tert.-butyL 2,3-epoxypropyL ether, 3nethoxy-2,2-dimethyLene-poxypropane, 1,2-butyLene oxide, 2,2-dimethyL oxiran, 2,3-dimethyL oxiran, ethyLene oxide.

The compounds of the formulae VI and VII are known.

The reaction is carried out by heating a mixture of the starting compounds in a diLuent and water in the presence of bases and if appropriate in the presence of a catalyst.

Le A 26 281 22

C,

The reaction is carried out at temperatures from 0 to 200 0 C, in particular at 50 150 0

C.

DiLuents which may be mentioned are: pentane, hexane, heptane, cyclohexane, petroleum ether, benzine, ligroin, benzene, toluene, xylene, diethy ether, dibutyL ether, diglycol dimethyl ether, dioxane, dimethyL sulphoxide, water.

Bases which may be mentioned are: S alkali metal hydroxides, alkali metal carbonates, alkaline 15 earth metaL hydroxides and alkaline earth metal carbona ates.

Catalysts which may be mentioned are: lrft tetrabutyammonium bromide, tetrabutyammonium hydrogen sulphate, tetrabutyammonium iodide, triethyl-benzylammonium chloride (TEBA), methyl (Cg-C 10 )-ammonium chloride (Adogen 464), hexadecyl-tributylphosphonium bromide, tetraethylammonium iodide.

At least 2 moles of compound of the formula VII are employed per mole of the compound VI.

When the reaction is compLete, working-up is carried out as follows: Le A 26 281 23 :j

:A.

Le A 26 281 10 I The organic phase is separated from the water phase and dried, for example'over sodium sulphate, the organic diluent is then distilled off, and the compounds of the formula II are then purified from the residue in a customary manner, for example by distillation.

The compounds of the formula VI are reacted with compounds of the formula VIII by heating a mixture of the starting compounds in a diluent and water in the presence of bases and catalysts.

444 4 4 44 4 44 44

II

4 44 This type of reaction is preferably chosen in order to obtain those compounds of the formula I in which R 3 represents radicals other than hydrogen.

The reaction is carried out at temperatures from 0 to 2000C, in particular at 50 1500C.

Diluents which may be mentioned are: pentane, hexane, heptane, cyclohexane, petroleum ether, benzine, ligroin, benzene, toluene, xylene, diethyl ether, dibutyl ether, diglycol dimethyl ether, dioxane, dimethyl sulphoxide.

Bases which may be mentioned are: alkali metal hydroxides, alkali metal carbonates, alkaline earth metal hydroxides and alkaline earth metal carbonates.

Le A 26 281 24 Le A e, 4 I- I I 77122i7~.

4 Catalysts which may be mentioned are: tetrabutylammonium bromide, tetrabutylammonium hydrogei sulphate, tetrabutylammonium iodide, triethyl-benzylammonium chloride (TEBA), methyl (Cg-C 0 o)-ammonium chl ide (Adogen 464), hexadecyl-tributylphosphonium bromid tetraethylammonium iodide.

The compounds VI and VIII are employed in an equimolar ratio.

n ore, When the reaction is complete, working up is carried out as follows:

IT

The organic phase is separated from the water phase and a o dried, for example over sodium sulphate, and the organic 4 4 41 diluent is then distilled off, and the compounds of the formula II are purified from the residue in a customary S manner, for example by distillation.

S 4 As already mentioned, the active compounds according to the invention have an insecticidal action, in particular against fleas. They are employed for controlling fleas in pets, such as dogs or cats, and in the environment of the pets.

The active compounds are applied directly or in the form of suitable preparations, dermally, enterally or parenterally, or by treating the environment, or with the aid of shaped articles containing the active compound, such as, Le A 26 281 25 4 for example, bands, neckbands, limb bands, marking devices.

Dermal application is carried out for example in the form of dipping, spraying, pc.ring-on, spotting-on and dusting.

I ei Examples of preparations for dermal application are solutions, suspension concentrates and emulsion concentrates, and also microemulsions which are diluted with water prior I to use, pouring-on formulations, powders and dusts, aero- 10 sols and shaped articles containing the active compound.

Solutions, suspension concentrates and emulsion concentrates and also microemulsions which are diluted with water prior to use, powders, dusts and aerosol formula- 15 tions are employed for treating the environment of the pets.

S These preparations are prepared in a known manner, for example by mixing the active compound with extenders, that is to say for example Liquid solvents, if appropriate using surface-active substances, that is to say emulsi- I: fying agents and/or dispersing agents. If water is used as an extender, it is also possible to use for example organic solvents as auxiliary solvents.

The liquid diluents include, besides water, alcohols, such as methanol, ethanol, isopropanol, n-butanol, amyl alcohol, octanol; glycols, such as propylene glycol, 1,3-butylene glycol, ethyl glycol or dipropylene glycol'monomethyl ether; Le A 26 281 26 glycerol; aromatic alcohols, such as benzyl alcohoL; carboxylic acid esters, such as, for example, ethyl acetate, benzyl benzoate, butyl acetate, propylene carbonate or ethyl Lactate; aliphatic hydrocarbons, such as paraffins, cyclohexane, methylene chloride or ethylene chloride; So,, aromatic hydrocarbons, such as xylene, toluene, alkylnaphthalenes or chlorobenzenes; ketones, such as, for example, acetone and methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; natural and synthetic mono- and tri-glycerides with natural fatty acids, such as cottonseed oil, groundnut oil, maize germ oil, olive oil, castor oil or sesame oil; furthermore dimethyl sulphoxide, dimethylacetamide, dio 15 methylformamide, N-methylpyrrolidone, dioxane or 2,2-dimethyl-4-oxymethyL-1,3-dioxolane.

S 9e 0 6 8 o The surface-active substances include: emulsifiers and wetting agents, such as anion-active surfactants, for example alkylsulphonates, alkyl sulphates, G"o arylsulphonates, sodium lauryl sulphates, fatty alcohol o ether sulphates, the monoethanolamine salt of mono/dialkyL polyglycol ether orthophosphoric ester or calcium alkylarylsulphonate; cation-active surfactants, for example cetyltrimethylammonium chloride; ampholytic surfactants, for example disodium N-lauryl beta-iminodipropionate or lecithin; non-ionogenic surfactants, for example polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, poly- Le A 26 281 27 YIL~LI~-~LI-L~ iC~ ioxyethyLated sorbitan monostearate, glycerol monostearate, polyoxyethylene stearate, alkyLpheno polyglycol ethers, polyoxyethyated sorbitan monopalmitate, polyoxyethylene lauryl ether, polyoxyethylene oleyL ether, poLyoxyethylene mannitan monolaurate, alkyl polyglyco ethers, oleyL poly- Sglycol ethers, dodecyl polygLycoL ethers, ethoxylated nonylphenol or isooctyLphenolpoyethoxyethanol.

Moreover, the preparations can contain: adhesives, for example carboxymethylcellulose, methylcellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinylpyrrolidone, polyvinyl alcohol, methyl vinyl ether/maleic anhydride copolymers, polyethylene glycols, paraffins, oils, waxes, hydrogenated castor oil, lecithins and synthetic phosphoLipids.

The preparations can contain colourants, such as inorganic pigments, for example iron oxide, titanium oxide, Prussian Blue, and organic pigments, such as alizarin, azo and o metal phthalocyanine dyes.

The preparations can contain spreading agents, for example silicone oils of various viscosities, fatty acid esters, such as ethyl stearate, di-n-butyl adipate, hexyl laurate, dipropylene glycol pelargonate, esters of a branched fatty acid of medium chain length with saturated fatty alcohols

C

16 -1 8 isopropyl myristate, isopropyl palmitate, caprylic/capric acid esters of saturated fatty alcohols of chain length C 12

-C

18 isopropyl stearate, oleyl oleate, Le A 26 281 28 decyl oleate, ethyl oleate, ethyl Lactate, waxy fatty acid esters, dibutyl phthalate, diisopropyl adipate, ester mixtures related to the latter and the like; triglycerides such as caprylic/capric acid triglyceride, triglyceride mixtures with vegetable fatty acids of chain length C 8

-C

12 Sor other specially selected natural fatty acids, mixtures S. of partial glycerides of saturated or unsaturated fatty acids which may contain hydroxyl groups, monodiglycerides of C 8

/C

10 -fatty acids and others; fatty alcohols such as isotridecyl alcohol, 2-octyldodecanol, cetylstearyl alcohol or oleyl alcohol.

To prepare powders and dusts, the active compound is mixed with suitabLe carriers, if necessary using additives, and 0 O 15 shaped as desired.

Carriers which may be mentioned are all physiologically acceptable solid inert substances. Inorganic and organic substances are used. Inorganic substances are optionally 20 crushed and fractioned, for example synthetic and natural oo Q :o ground minerals such as kaolins, talc, chalk, diatomaceous earth, common salt, aluminas, silicas, clays, precipitated or colloidal silicon dioxide. Organic substances are Lactose, starch and cellulose or cellulose derivatives.

S Auxiliaries are preservatives, antioxidants or colourants which have already been mentioned further above.

Other suitable auxiliaries are lubricating and slipping Le A 26 281 29 agents, such as, for example, magnesium stearate, stearic acid, talc or bentonites.

The active compounds may be present in the form of their o 5 abovementioned solid or liquid formulations, and also 0 encapsulated.

8 o0 S The active compounds can also be used in the form of an 1 aerosol. For this purpose, the active compound is finely distributed under pressure in a suitable formulation.

0 f It can also be advantageous to apply the active compounds in formulations which release the active compound slowly.

88 As such formulations, active compound-containing shaped o 15 articles, such as, for example, plates, tapes, strips, Sso neckbands, limb bands or marking devices may be mentioned.

o o 0 00 The active compounds can be present in the formulations on their own or in a mixture with other active compounds B.Bo 20 or synergists.

0 0 Formulations which are applied directly contain between 7 and 5 per cent by weight, preferably between 10 4 and 1 per cent by weight, of active compound.

Formulations which are only used after further dilution contain 1 95 per cent by weight, preferably 5 90 per cent by weight, of active compound.

Le A 26 281 30 YLLICi- ~-I~3LC Formulation ExampLes 1. Preparation of an emulsion concentrate a) Active compound of Example 1 Q 6 8 6r 46 ;1(

*I

4 1 (100 Non-ionic emulsifier (Emulgator 368 alkylaryl polyglycol ether MW approx. 1165) Dipropylene glycol monomethyl ether 25.00 g 25.00 g to 100.00 ml 4* 6 aQ 0

O

25 Preparation The substances are weighed together and stirred until a clear solution has formed.

The solution is diluted to its application concentration prior to use.

b) Active compound of Example 2 (100 Polyoxyethylene stearate Sorbitan sesquioleate Water Polyethylene glycol 200 to 100 ml Preparation and use as in la 1.00 g 0.50 g 0.40 g 4.00 g Le A 26 281 31 i. -s 2. Preparation of a pour-on formulation a) Composition Active compound of Example 1 (100 5.00 g Isopropyl myristate 30.00 g 1 2-Octyldodecanol 20.00 g .rI Isopropanol to 100 ml Preparation: 0 0 1 S° 15 The substances are weighed together and stirred until °o a clear solution has formed.

Sb) Composition Active compound of Example 1 (100 0.50 g o 0 Silicone oil 100 30.00 g Butyl acetate to 100 ml Preparation as in Example a) Le A 26 281 32 4% )1 -f r 3. Preparation of a microemuLsion Active compound of Example 1 (100 Eumulgin B3 (aLkylaryL polyglycol ether) CetioL HE® (polyoL fatty acid ester) IsopropyL myristate 13.00 g 30.00 g 30.U0 g 5.00 g 3.00 g Benzyl alcohol e o o o *o 15 0 0 0 0 0 0 09 0 *20 Water to 100 ml Preparation: The active compound is dispersed in the lipophilic components (Eumulgin, Cetiol, benzyl alcohol and isopropyl myristate).

The mixture is warmed to 60 0 C, water of the same temperature is admixed, and the mixture is cooled. The microemulsion formed superficially resembles a clear solution.

Le A 26 281 33 4. Preparation of a spray formulation Composition Active compound of Example 1 (100 20 g Emulgator ToximuL 7 g (mixture of calcium alkylbenzenesulphonate and non-ionogenic emulsifiers and methanol) Emulgator Toximul 5 g (mixture of calcium alkylbenzene- *at o 15 sulphonate and non-ionogenic emulsi- C.o e fier and methanol) Sovesso 200' to 100 mL (alkylnaphthalene mixture of high- 20 boiling mineral oil fractions) 4 S Preparation: The active compound is weighed together with the re- S 25 maining components, and the mixture is stirred and diluted with water to the application concentration prior to use.

Le A 26 281 34 Use Examples A. In-vitro test on fleas (all developmental stages) S 5 Test object: All stages (eggs, Larvae, pupae, adults) of Sr Ctenocephalides felis STesting procedure S 10 The substance to be tested is distributed homogeneously in blood meal in the concentration desired. Flea eggs which had been collected from flea-infested cats are transferred into this mixture of blood meal and test substance, and incubated at 80 relative atmospheric humidity and 250C.

So After the development time of 3 4 weeks has elapsed, it 9C o o. is determined if adult fleas have developed. 100 action signifies that no adult fleas have been determined and 0% that living adult fleas have been determined.

At a concentration of 5 ppm, the compound of Example 3 shows an action of 100 Le A 26 281 35 B. In-vivo test on fLeas (all developmental stages) Test object: Eggs, larvae, pupae of Ctenocephalides felis in the environment of dogs/cats, adult fleas on dogs/cats.

a t ae 4 Testing procedure Beds, in boxes, of dogs/cats which are free of fleas are sprayed with the substance to be tested at the desired application concentration. At defined points in time i after the application, eggs of Ctenocephalides felis, which had been collected from infested cats, are transo o ferred to the beds of the dogs/cats. It is determined if, and at which point in time, the dogs/cats in the o boxes are infested by adult fleas.

100 action here denotes that dogs/cats do not show infestation with fleas, and 0 action that dogs/cats are o o 20 infested by fleas.

The active compound of Example 3 shows an action of 100 Le A 26 281 36 y 7 7 7.

t Preparation Examples Process 2a: General procedure: A mixture of 1 mol of compound of the formula II and of the approximately 1.1- to 3-fold molar amount of compound of the formula III, the approximately 6-fold molar amount of Na-OH powder, the approximately 1.1-fold amount of

K

2 C0 3 powder and of the approximately 0.02-fold amount of the phase transfer catalyst tris-(2-(2-methoxyethoxy)ethyl)-amine is refluxed in toluene for approximately 36 '4 hours. After cooling, the toluene phase is washed with *I 15 water, dried over Na2S04 and concentrated in vacuo. The product formed is further purified by distillation using a bulb tube. The following are obtained in accordance with this procedure: 4 t

S

Example 1 H-8 H-7 H-6 H-4 1 H-NMR, DMSO-d 6 8.18 ppm 7.71 ppm H-4') 5.40 ppm 1H, HB); 4.81 ppm 1H, HA); 2.21-1.72 ppm 6H); 7.37-6.81 ppm 11H,9aromat. H, H-3' Le A 26 281 37 i..

ExampLe 2 H

H

H-9 H-1i 0-C H-8B 5 H-7

HN

H-6 H-4 3 H-NMR, DMSO-d 6 lr

E

r ri (9(

C'

8.16 ppm 7,37-6,90 ppin Cm, 10H,-9aromat. H and 7.68-7.62 ppm (m, 6.67 (d J, 8.3 HZ, 4.46-4.39 ppm Cm, HA) 5.20 ppm Cm, H 6 2.11 ppm Cm, 2H); 1.7 ppm Cm, 1.52-1.40 ppm 4H).

H-4' 5.27- 2H) *e I 44 4i 4a 4 4 4 44 4a 4 4. 4.

o aI,' 444, 44 ExampLe 3 3' 4' H-9 H-1 H-7 -3 6- H-6 H-4 1 H-NMR (DMSO-d 6 8.15 ppm 7.73-4.67 ppm Cm, 7.37-6.90 ppm Cm,-E3, 9aranat.H 6.82 ppm Cm, 4.41-4.48 ppm 2H); 4.11-4.08 ppm 2H); 3.83-3.79 ppm Cm, 4H).

Le A 26 281 38 I Example 4 3' 4' H-9 H-1 H-8 0-CH2CH2-0-CH2CH2-0-CH2CH2-0- H-7 H-3 6' H-6 H-4 1 H-NMR, DMSO-d 6 8.16-8.13 ppm 7.72-7.66 ppm 7.37- 6.90 ppm (10H,9aromat. H 6.83-6.8 ppm 4.39-4.35 ppm 2H); 4.08-4.05 ppm 2H); 3.77-3.73 ppm 4H); 3.61 ppm 4H).

g. 15 Process 2b: General procedure: 4 4 A mixture of approx. 20 mmoL of compound of the formula IV t 20 and of the approximately 1.5- to 2-foLd molar amount of o. t the compound of the formula V, of the approximately 0.05fold amount of the phase transfer catalyst (Adogen 464) is stirred for 18 hours at 50 to 70 0 C in 30 ml of 45 strength NaOH and 30 ml of methylene chloride. After cooling, the mixture is diluted with 0.5 L of water and extracted three times using three 50 ml portions of methylene chloride, the methylene chloride phases are concentrated, and the residue remaining is recrystallized from diethyl ether. The following is obtained in accordance with this procedure: Le A 26 281 39 Example S-

CH

2

CH

2

-CH

2 0-

NH

2 yellow crystals, melting point 47-48 0

C

Example 6 4.2 mmol (1.4 g) of the compound of Example 5 are refluxed for 18 hours in 80 ml of dry acetone with 6.4 mmol (1.2 g) of 3,4-dichlorophenyl isocyanate. The solvent is distilled off under reduced pressure, and the residue is recrystallized from cyclohexane. Yield 2.0 g (approx. 92 S Example 7 3.6 mmol (1.2 g) of the compound of Example 5 are refluxed for 18 hours in 80 ml of dry acetonitrile with 5.7 mmol (1.2 g) of 4-phenoxyphenyL isocyanate. After the solvent Shas been distilled off in vacuo, the residue is recrystallized from cyclohexane. Yield 1.4 g (approx. 72 Preparation of the starting compounds of the formula II in accordance with process 4: 3 to 5 mol of epoxide of the formula VII are stirred in the presence of 2 to 3 mol NaOH, 0.005 to 0.02 mol of phase transfer catalyst tetrabutylammonium bromide in a mixture of 1 L of toluene and approx. 340 ml of water at Le A 26 281 40 to 130 0 C for 48 hours per mot of compound of the formula VI. After the mixture has cooled, saturated NaCL solution is added, and the toluene phase is separated off.

Toluene is distilled off in vacuo, and the residue distilled. Alternatively, the crude production of the reaction can be reacted further immediately without previous purification.

The following are obtained in accordance with this procedure: Example a) H-9 H-i HA HB H-8 O- OH H-7 H- H-6 H-4 t *1

I

H-NMR (DMSO-d 6 7.37-6.91 ppm 9 aromat. 5.05 ppm OH); 4.43- 4.41 ppm and 4.07 ppm 2H, HA and HB); 2.13-1.27 6H, cyclopentane ring).

Example b) H-9 H-i OH H-7 2H I H30-6 H-4 3 H-NMR (DMSO-d6): Le A 26 281 41 7.37-6.90 ppm 9 aromat. 4.91 ppm J 4.6-Hz, OH); 4.01-3.94 ppm(m, HA or HB); 3.56-3.49 ppm HA or HB); 1.99-1.26 ppm 8H).

Example c) 14 g of 4-hydroxydiphenyl ether are refluxed for approx.

24 hours with 25 g of 2-(2-chloroethoxy)-ethanol in the presence of 30 g of K 2 C0 3 and 4 g of KJ in 250 ml of acetonitrile. After the mixture has cooled, the solvent is distilled off, the residue remaining is washed with sodium hydroxide solution and toluene, and the toluene phase is subsequently dried over Na 2

SO

4 The solvent is again distilled off. In accordance with this procedure, 15 the following are obtained: H-9 H-1 H-8 0- 2 CH2CH 0 -CH-CH2 0

H

H-7 O^ H-3 H-6 H-4 Boiling point: 250°C/0.2 mbar.

Yield: 9.8 g (48 of theory) Example d) SO-CH2CH2-0-CH2CH2-0-CHCH2CH-OH Yield: 6.0 g (29% of theory) Boiling point: 250 0 C/0.1 mbar Le A 26 281 42

Claims

1. Substituted py e invention are as follows: ridines of the formula I R 3 R 4 I I )O-CH. ,H 5 I ts 0, S, NH, -CH 2 -CHCH 3 I-, in which X represer C CH 3 2 Y represents Lene which gen, straight-chain or branched alky- is optionally interrupted by oxy- 4 4f 4,( R1 represents identical or different radicals from the group comprising hydrogen, halogen, alkyl, alkoxy, halogenoalkyl, R 2 represents identical or different radicals from the group comprising hydrogen, halogen, alkyl, alkenyL, halogenoalkyl, alkoxy, alkyl- thio, halogenoalkoxy, halogenoalkylthio, R3 represents hydrogen, alkyl, halogenoalkyL, alkoxyalkyl, alkenoxyalkyl, alkenyl, alkinyl, R4 represents the radicals indicated for R3 Le A 26 281 43 i_. A 3 and R 4together can represent a direct bond, R 5 represents hydrogen, haLogen, aLkyl, haLogeno- alkyl, aLkoxy, amino, alkylureido, alkylamino, dialkylamino, phenylureido, substituted phenylureido, morpholinyl, dixethylmorpholinyl, piperazinyl, N- alkylpiperazinyl, and their salts with acids.

2. Processes for the preparation of the substituted pyridines of the formula I R

3 R 4 2 I I in which 1 2 3 4 5 Y, R F R I R ,R and R are as defined in P050 claim 1, Le A 26 281 44 9and their saLts with acids, which are characterized *o in that *944 a) compounds of the formuLa 11 I ,CH-OH X P2 y Le A 26 281 45 in which R 1 R 2 R 3 R

4 X, Y have the abovemen- tioned meaning are reacted with halogenopyridines of the SformuLa III Hal III Tin which Hal represents halogen and

5 R has the abovementioned meaning, or 4 4* I o b) compounds of the formula IV It R 3 R4 IIJ--0CH, ,CH-Hal IV in which R 1 R 2 R R 4 X, Y have the abovemen- tioned meaning and Hal represents halogen are reacted with hydroxypyridines of the Le A 28 281 46 i: 0181s:AB 47 formula V V in which R has the abovementioned meaning. Agent for controlling insects, in particular fleas, characterized in that it contains at least one substituted pyridine of the formula I according to Claim 1 in admixture with at least one extender and/or surface active substance.

6. Method for controlling insects, in particular fleas, I characterized in that substituted pyridines of the Sr formula I according to Claim 1 are allowed to act on 'I fleas, their hosts and/or their habitat. 0 Process for the preparation of agents for controlling S<insects, in particular fleas, characterized in that substituted pyridines of the formula I according to Claim 1 are mixed with extenders and/or surface-active substances. DATED this 3rd day of September, 1991. BAYER AKTIENGESELLSCHAFT By Its Patent Attorneys ARTHUR S. CAVE CO.