DE2725763A1 - SUBSTITUTED ISOXAZOLINES AND FUNGICIDES CONTAINING THEM - Google Patents

Description

U \ - ~ yv. ' .-1 · ■ · ■ · ■■■; ■■; ·

X-4379

Eli Lilly and Company, Indianapolis, Indiana, USA

Substituted isoxazolines and fungicides containing them

middle

709851/0976

The invention relates to a class of new 2-isoxazolines, which are substituted in position 3 by aryl and in position 5 by methyl or ethyl, and which are suitable for combating by microorganisms, especially for combating fungal leaf phytopathogens.

Isoxazolines related to the present compounds go from Gazz. Chim. Ital. 80, 741-44 (1950), and these are compounds which have phenyl groups in position 3 and methyl groups substituted in position 5 exhibit. In J. Med. Chem. 10, 411-18 (1967) and in JA-PS 42-9146 isoxazoles are described which are in position 3 are substituted by phenyl and in position 5 by aminomethyl.

Isoxazolyl carbamates with fungicidal activity are known from US Pat. No. 3,629,474, and the same is stated in FR Pat. No. 22 15 219 Efficacy for Thiocarbamoylisoxazolidine described.

The invention now relates to new microbiocides of the formula I

- (CHa) _n -R

for -NCS, cyano, amino, aminohydrohalide, -NHCSN (R ¹ R ² ), -NHCO ₂ (C ₁ -C ₃ alkyl) or a radical

the formula

COCH _{3 s} _ _c _cH

stands,

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η stands for 1 or 2,

1 2

R and R independently of one another are hydrogen or C ₁ -C ₃

Mean alkyl or

1

R is hydrogen and R is amino or

1 2

R and R together with the nitrogen atom to which they are attached are, form morpholino, piperidino or pipera zino,

R represents hydrogen or phenyl,

R naphthyl, 2-pyridyl or a radical of the formula

R ⁵

is,

Cr- -j

wherein the substituents R, R and R independently of one another represent chlorine, bromine, fluorine, nitro, trifluoromethyl, C ₁ -C ₂ alkoxy, C ..- C ₂ alkylthio, C 1 -C 4 alkyl, hydroxy, phenyl, benzyloxy or hydrogen ,

with the proviso that at most one of the substituents R, R or R is phenyl or benzyloxy means, and with the further provisos that

(1) no more than one of the substituents

R ⁵ , R ⁶ and R ^{7 represent} tert-butyl if one of the substituents R, R or R is hydroxy, alkoxy or benzyloxy, and that

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272S7b3

(2) if one of the substituents R ⁵ , R ⁶ or R is chlorine, the hydroxyl, alkoxy or benzyloxy groups are then arranged in the ortho position to this.

The invention further relates to a process for the preparation of substituted isoxazolines of the formula given above I directed, which is characterized in that a chlorinated oxime of the formula II

Cl
R ⁴ -C = NOH II

wherein R has the above meaning with a compound of the formula III

η η;

R ³ -C = C- (Cri ₂ ) _n -RI ¹¹ !

in which R and η have the above meanings and R is -NCS, cyano or -NHCO ₂ (C ₁ -C ₃ alkyl), to a compound of the formula I in which R is -NCS, cyano or -NHCO ₂ (C ₁ -C ₃ alkyl), reacts and optionally further

(1) a compound of the formula I in which R is -NCS with an amine of the formula IV

HN (R ¹ R ² ) IV j

12th
wherein R and R have the meanings given above, to

a compound of the formula I in which R is -NHCSN (R ¹ R ² ), or

(2) a compound of the formula I in which R is -NHCO ₂ (C ₁ -C ₃ alkyl) is hydrolyzed to a compound of the formula I in which R is amino or aminohydrohalide, or

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(3) a compound of the formula I in which R is -NHCSN (R ¹ R)

ι 2

stands, R is hydrogen and R is amino, with acetic anhydride, an acetyl halide or a mixture thereof to a compound of the formula I in which R is a radical of Formula I.

COCH "!

T a / S - C - CH

- | (, (ζ "3

^X N - NI

stands, implements.

The invention also relates to a method for reducing the adverse effects of fungal leaf phytopathogens, which is characterized in that the phytopathogens on the foliage of host plants with an effective Treated amount of one of the compounds described above. Finally, the invention also applies to fungicide Agents directed that contain the present compounds as active ingredients.

In the above formulas, the details C ₁ -C ₃ alkyl, C ₁ -C ₄ alkyl, C ₁ -C ₂ alkoxy or C ₁ -C ₂ alkylthio relate to radicals such as methyl, ethyl, isopropyl, butyl, tert .-Butyl, methoxy, ethoxy, methylthio or ethylthio. Hydrohalide is understood to mean hydrobromide, hydrochloride, hydrofluoride or hydroiodide.

All temperatures are measured in degrees Celsius.

Those compounds of the formula I given above in which R is -NCS and R is hydrogen represent a preferred class of compounds according to the invention, which characterized by a particularly good microbiocidal effectiveness.

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Further particular classes of compounds from formula I above are the following:

1. R means -NCS;

2. R is -NCS, cyano, NHCSN (R ¹ R ² ) OdCr-NHCO ₂ (C ₁ -C ₃ alkyl), wherein

A) the substituents R ¹ and R ^{2 are} hydrogen, C ₁ -C ₃ alkyl or amino,

1 2

B) the substituents R and R together morpholino,

Form piperidino or piperazino;

3. R is -NHCSN (R ¹ R ² ) OdSr-NHCO ₂ (C ₁ -C ₃ alkyl), wherein

1 2

A) the substituents R and R are hydrogen, C ₁ -C ₃ alkyl

or represent amino,

1 2

B) the substituents R and R together form morpholino, piperidino or piperazino;

4. R is cyano;

5. R stands for -NCS, amino, aminohydrohalide, -NHCSN (R ¹ R ² ) OdOr-NHCO ₂ (C ₁ -C ₃ alkyl), wherein

1 2

A) the substituents R and R are hydrogen, C ₁ -C ₃ alkyl

or are amino,

1 2

B) the substituents R and R together form morpholino, piperidino or piperazino;

6. R ³ represents hydrogen;

7. R is phenyl;

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8. R ⁴ is 2-pyridyl;

9. R denotes naphthyl or a radical of the formula

4th
10. R is a radical of the formula

11. R has the meaning given above under 6 and

A) the substituents R and R have the above under 1 and

8 meanings given,

B) the substituents R and R have the above under 1 and

9 meanings given,

C) the substituents R and R have the above under 1 and

10 meanings given,

D) the substituents R and R have those above under 2A and

8 meanings given,

E) the substituents R and R have the above under 2A and

9 meanings given,

F) the substituents R and R have those above under 2A and

10 meanings given,

4 the substituents R and R

8 meanings given,

4 the substituents R and R

9 meanings given,

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4th
G) the substituents R and R have the above under 2B and

4th
H) the substituents R and R have the above under 2B and

2/25763

4 I) the substituents R and R have the above under 2B and

10 meanings given,

4 J) the substituents R and R have the above under 3 and

8 meanings given,

4 K) the substituents R and R have the above under 3 and

9 meanings given,

4 L) the substituents R and R have the above under 3 and

10 meanings given,

4 M) the substituents R and R have the above under 4 and

8 meanings given,

4 N) the substituents R and R have the above under 4 and

9 meanings given,

4 0) the substituents R and R have the above under 4 and

10 meanings given,

4 P) the substituents R and R have those above under 5A and

8 meanings given,

4 Q) the substituents R and R have those above under 5A and

9 meanings given,

4 R) the substituents R and R have the above under 5A and

10 meanings given,

4 S) the substituents R and R have the above under 5B and

8 meanings given,

4 T) the substituents R and R have those above under 5B and

9 meanings given,

4 U) the substituents R and R have those above under 5B and

10 meanings given;

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12. R has the meaning given above under 7 and

A) the substituents R and R have the above under 1 and

8 meanings given,

B) the substituents R and R have the above under 1 and

9 meanings given,

C) the substituents R and R have the above under 1 and

10 meanings given,

D) the substituents R and R have those above under 2A and

8 meanings given,

E) the substituents R and R have the above under 2A and

9 meanings given,

F) the substituents R and R have those above under 2A and

10 meanings given,

G) the substituents R and R have the above under 2B and

8 meanings given,

4th
H) the substituents R and R have the above under 2B and

9 meanings given,

4th
I) the substituents R and R have the above under 2B and

10 meanings given,

4th
J) the substituents R and R have the above under 3 and

8 meanings given,

4th
K) the substituents R and R have the above under 3 and

9 meanings given,

4th
L) the substituents R and R have the above under 3 and

10 meanings given,

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4 M) the substituents R and R have the above under 4 and

8 meanings given,

4 N) the substituents R and R have the above under 4 and

9 meanings given,

4 0) the substituents R and R have the above under 4 and

10 meanings given,

4 P) the substituents R and R have those above under 5A and

8 meanings given,

4 Q) the substituents R and R have those above under 5A and

9 meanings given,

4 R) the substituents R and R have the above under 5A and

10 meanings given,

4 S) the substituents R and R have the above under 5B and

8 meanings given,

4 T) the substituents R and R have those above under 5B and

9 meanings given,

4 U) the substituents R and R have those above under 5B and

10 meanings given.

Typical isoxazolines of the formula I are given below Links. However, these compounds are not a comprehensive list, but are intended for the agrochemist only allow a better understanding of the invention.

5- (2-cyanoethyl) -3- (1-naphthyl) -2-isoxazoline 5-aminomethyl-3- (2-naphthyl) -2-isoxazoline

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5- (2-aminoethyl) -4-phenyl-3- (2-pyridyl) -2-isoxazoline hydrobromide

5- (2-ethoxycarbonylaminoethyl) -3- (2,4,6-trichlorophenyl) -2- -isoxazoline

3- O-bromo-S-chlorophenyl) -S-propoxycarbonylaminomethyl ^ - -isoxazoline

N - // 3- (2,4-difluorophenyl) -2-isoxazolin-5-yl./Inethyl./-N- (5- methyl-1,3,4-thiadiazol-2-yl) acetamide

N- / 2- / 3- (2-hydroxy-5-nitrophenyl) -2-isoxazoline-5-yj./äthyj./- -N- (5-methyl-1,3,4-thiadiazol-2-yl) acetamide

5- (2-isothiocyanatoethyl) -3- (2-trifluoromethylphenyl) -4-phenyl- -2-isoxazoline

1-ethyl-3- / 2- / 3- (2 _/ 6-dinitro-4-trifluoromethylphenyl) -4-phenyl- -2-isoxazolin-5-yl_ / ethyl. / Thiourea

1-propy1-3- / 2- / 3- (3-benzyloxy-5-methoxyphenyl) -2-isoxazoline- -5-yl / ethyl / thiourea

1-ethyl-1-methyl-3- / 2- / 3- (3-chloro-2-ethoxyphenyl) -2-isoxazoline- -5-yl ^ / ethyl. / Thiourea

1,1-diethy1-3 - // 3- (3,4-bis (methylthio) phenyl) -2-isoxazoline- -5-yVmethyl./thiourea

- (3-nitro-5-phenylphenyl) -2-isoxazolin-5-yl./methyabei./thiourea

1-ethyl-3 - // 3- (3-bromo-2,5-dihydroxyphenyl) -4-phenyl-2-isoxa zolin-5-y ^ / methyj. / thiourea

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N - // 3- (3-chloro-5-ethyl-4-hydroxyphenyl) -2-isoxazolin-5-yjL / -methy ^ / - 4-morpholine thiocarboxamide

N- / 2- / 3- (2,4-diisopropylphenyl) -2-isoxazolin-5-y_l / ethy] _l / -1-piperidine thiocarboxamide

N - // 3- (2,4,6-trimethylphenyl) -2-isoxazolin-5-y] ./ methy] y-1 -piperazinthiocarboxamide

3- (4-benzyloxy-3-propylphenyl) -5-isothiocyanatomethyl-4- -phenyl-2-isoxazoline

5-aminomethy 1-3- / 3- (tert -butyl) -5-nitrophenyl ^ / - 2-isoxazoline- -Hydrofluoride

1-methyl-3- / 2- / 3- (2,5-diethylphenyl) -2-isoxazolin-5-y] ./ ethy] _L / -thiourea

3- (2-chloro-6-nitrophenyl) -5-ethoxycarbonylaminomethyl-4- -phenyl-2-isoxazoline

3- (3-chloro-5-nitrophenyl) -5- (2-isothiocyanatoethyl) -2-isoxazoline

1- / 2- / 3- (3,5-bis (trifluoromethyl) phenyl) -2-isoxazolin-5-yl / ethy1 / thiourea

1- // 3- (2-Hydroxy-4-trifluoromethyl! Phenyl) -2-isoxazolin-5-yl / -methy] ./ thiourea

S-aminomethyl-3- (2-chloro-5-ethylthio-3-phenylphenyl) -4-phenyl- -2-isoxazoline

S-isothiocyanatomethyl-S-O-methylthio-S-nitro-S-phenylphenyl) -2-isoxazoline.

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Preferred compounds from the above formula I are as follows:

S-isothiocyanatomethyl-S- (4-chlorophenyl) -2-isoxazoline,

S-isothiocyanatomethyl-S- (4-trifluoromethylphenyl) -2-isoxazoline,

3- (2,6-dichloropheny1) -5-isothiocyanatomethy1-2-isoxazoline, S-isothiocyanatomethyl-S- (4-methylphenyl) -2-isoxazoline and B-isothiocyanatomethyl-S- (2-pyridyl) -2-isoxazoline.

The compounds of the formula I can be prepared from readily available starting materials. The respective Manufacturing processes are based on a correspondingly sub-

4 substituted arylaldehyde, a benzaldehyde, if R is for

Phenyl or substituted phenyl, a naphthalene

4th
hyd, if R is naphthyl, or a pyridylaldehyde, if

R ^{4 represents} 2-pyridyl.

To do this, the aldehyde is first mixed with hydroxylamine, preferably a hydrohalide salt of hydroxylamine to give the corresponding aldehyde oxime. Do you use that Hydroxylamine in the form of a hydrohalide salt, then you should work with an acid acceptor, for example a tertiary amine, an alkali alkoxide or an inorganic base such as sodium carbonate, sodium bicarbonate or potassium hydroxide. An aqueous alkanol is preferably used as the solvent, but can Use other solvents as well, such as diethyl ether or chloroform. Preferably it is at reflux temperature worked.

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-4a-

For chlorination of the OC carbon atom in the above manner The aldehyde oxime obtained is then simply brought to this compound in a solvent such as chloroform with free Chlorine together. Low temperatures of about 0 ° C. to about 10 ° C. are preferred here.

The above chlorination stage often also leads to a certain chlorination of the phenyl ring of a benzaldoxime, in particular when hydroxy, alkoxy or benzyloxy substituents are present. Using such a Corresponding poly-substituted intermediates can also be prepared without difficulty, such as from the chlorination related examples.

The chlorinated oximes of the formula I obtained in the above manner are the direct precursors of all compounds according to the invention. They are unstable in their pure form and are therefore best used without cleaning.

The isothiocyanates, namely the preferred compounds according to the invention, are prepared by bringing the chlorinated Oxime at low temperature with an allyl or crotyl isothiocyanate of formula III in the presence of a strong base, preferably triethylamine. Should be the product you want in position 4 (substituent R) be phenyl-substituted, then one starts from a cinnamyl isothiocyanate or 4-phenyl -3-butenyl isothiocyanate of the formula III. The preferred solvent for carrying out the reaction is diethyl ether, however, other typical inert solvents such as tetrahydrofuran, benzene or the can also be used Alkanes. Triethylamine is preferred as the strong base. Desired

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If necessary, other typical strong bases can just as well be used, such as pyridine, sodium hydroxide, alkali alkoxides or lithium carbonate.

The reaction should expediently be carried out at temperatures in the range from 0 ° C. to 15 ° C., but it can can also be used at lower temperatures. The preferred order of addition of each reactant consists, as is usual in such reactions, in a combination of the isothiocyanate and the oxime in each case Solvent, subsequent temperature reduction and subsequent very slow addition of the base with stirring.

The same process is also used for the preparation of those compounds of the formula I in which R is cyano or alkyl carbamate by using a corresponding crotyl or allyl cyanide or carbamate as the isothiocyanate Formula III used.

To prepare the thioureas of the formula I, one uses the corresponding isothiocyanate of the formula I simply with a corresponding amine of the formula IV. This can be done at Temperatures from room temperature to the reflux temperature are used, solvents such as diethyl ether or alkanols.

Those compounds of the formula I in which R is amino are prepared by adding the corresponding carbamate of formula I hydrolyzed, for example, with a strong mineral acid. Used as a mineral acid for example a hydrohalic acid, such as hydrochloric acid, then the corresponding aminohydrohalides are obtained. By neutralizing these hydrohalides with

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Bases lead to the corresponding free amino compounds.

To prepare the methylthiadiazoles of the formula I, sets

one the corresponding thioureas of the formula I, at

2
where R stands for amino, with acetic anhydride, a

Acetyl halide or a mixture of acetic anhydride and an acetyl halide. This is preferably done under Reflux temperature worked in dioxane as a solvent.

The invention is further illustrated by the following examples. The compounds obtained according to these examples are by nuclear magnetic resonance analysis, elementary microanalysis, and in appropriate cases also identified by infrared analysis or mass spectroscopy.

The first example illustrates a typical method of manufacture an isoxazolinyl isothiocyanate.

Example 1 S-Isothiocyanatomethyl-β- (4-chlorophenyl) -2-isoxazoline

70 g (1 mol) of hydroxylamine hydrochloride and 54 g of sodium methoxide are added to 500 ml of isopropanol and 250 ml of water. That The reaction mixture thus obtained is then admixed with 130 g of 4-chlorobenzaldehyde and stirred overnight at room temperature. A large amount of water is then added to the whole and the resulting precipitate is filtered off and extract the filtrate with chloroform. The organic Layer is then dried over sodium sulfate and applied to the Evaporated half of its volume. This concentrate

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then three volumes of hexane are added and the 4-chlorobenzaldoxime thus obtained is finally filtered off. The yield is 101 g.

The benzaldoxime prepared in the above manner is dissolved in 1 liter of chloroform, whereupon the solution is brought to 5 to 10 ° C cools and introduces dry chlorine gas into them. By evaporating the resulting yellow solution to dryness and Washing the residue with hexane gives 123 g of OC / 4- dichlorobenzaldoxime.

20 g of the above intermediate are dissolved in 750 ml of anhydrous diethyl ether, and 15 g are then added to the solution Allyl isothiocyanate. The reaction mixture is cooled to 5 ° C and dropwise over a period of 1 hour with stirring with 15g of triethylamine in 125 ml of anhydrous Diethyl ether is added, the temperature being kept at 5 ° C. The mixture is then stirred overnight and left on Come to room temperature. The reaction mixture is filtered and the filtrate is evaporated in vacuo to give a viscous yellow oil is obtained, which partially crystallizes. The precipitate obtained in the filtration becomes the series after washed with acetone, water and chloroform, whereupon it is extracted with a mixture of chloroform and water. All of the chloroform is combined with the acetone used for washing and that from the evaporation of the filtrate obtained residue, whereupon the mixture is concentrated in vacuo and diluted with hexane. That way you get after filtering about 12 g of S-isothiocyanatomethyl-S- (4-chlorophenyl) -2-isoxazoline in crystalline form that melts at 118 to 120 ° C.

The following example illustrates the preparation of an isothiocyanatoethyl compound, where η stands for 2.

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Example 2 5- (2-isothiocyanatoethyl) -3-phenyl-2-isoxa2oline

23 g (X-chlorobenzaldoxime, prepared according to Example 1 above, they are combined with 17 g of crotyl isothiocyanate in 300 ml of diethyl ether. The solution is cooled to 15 ° C. and added dropwise 40 ml of triethylamine in 100 ml of tetrahydrofuran are added. The mixture is stirred at 15 ° C. for 24 hours and then filtered. The filtrate is washed with water and then evaporated to dryness. The residue is dissolved in chloroform, and the resulting solution is chromatographed on a column filled with polystyrene gel beads (2.5 cm diameter, 8 m length). The eluate is evaporated to dryness and the residue obtained is crystallized from diisopropyl ether / hexane around. In this way, 10 g of 5- (2-isothiocyanatoethyl) -3-phenyl-2-isoxazoline are obtained melts to 56 C. The microanalysis of this material gives the following values:

Analysis: 62 C. 5 H 1 2 N 1 3 S. calculated: 61 .04% 5 , 21 1 1 , 06 1 4th , 80 found: .77% , 02 , 93 , 03

Following procedures that are essentially the same as those described above are similar, the following compounds are also made. It is therefore only used for these examples the starting materials used and their amounts, as well as the characteristics of the compounds obtained thereafter cited.

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Example 3 S-Isothiocyanatomethyl-S-phenyl ^ -isoxazoline

By reacting 156 g of Oc-chlorobenzaldoxime with 125 g Allyl isothiocyanate gives 110 g of the compound mentioned in the title, which melts at 61 to 63.degree.

Analysis: CHNS

calculated: 60.53% 4.62 12.83 14.69 found: 60.81% 4.69 12.69 14.79

Example 4 5-Isothiocyanatomethyl-3- (2,4-dichlorophenyl) -2-isoxazoline

By chlorinating 34 g of 2,4-dichlorobenzaldoxime after Process described in Example 1 and subsequent reaction of the compound obtained in this way with 20 g of allyl isothiocyanate 6 g of the title compound are obtained in the form of an oily liquid.

Analysis: CKNS

calculated: 46.01% 2.81 9.76 11.17 found: 46.24% 2.72 9.85 11.06

Example 5 S-Isothiocyanatomethyl-S- (3-trifluoromethylphenyl) -2-isoxazoline

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To produce a chlorinated benzaldoxime, 18 g of 3-trifluoromethybenzaldehyde are used as a starting point and the resultant is used Then compound with 15 g of allyl isothiocyanate. In this way one arrives at 7 g of the title compound, which in Melts from 47 to 49 ° C.

Analysis: 50 C. 3 H 7th 9 N 1 1 S. calculated: 50 .35% 3 ,1 3 9 , 79 1 1 , 20 found: , 23% ,1 , 74 , 05

Example 6

3- (3-chloro-4-methoxy-5-methy! Phenyl) -S-isothiocyanatoir.ethyl-

-2-isoxazoline

By reacting 40 g of CK, S-dichloro ^ -methoxy-S-methylbenzaldoxime with 25 g of allyl isothiocyanate, 100 mg is obtained
the title compound, which melts at 108-108.5 ° C.

Analysis: C H N Cl

calculated: 52.61% 4.42 9.44 11.95

found: 52.39% 4.25 9.41 12.26

Example 7 S-IsothiocyanatoTT.ethyl-S- (2-naphthyl) -2-isoxazoline

By reacting 21 g of OC-chloro-ß-naphthaldoxime with 25 g
Allyl isothiocyanate, 1 g of the title compound is obtained in

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Form of an oily liquid. NMR multiplets at 3.28-4.15, 4.83-5.28 and 7.5-8.42 ppm.

Example 8 3- (2-Chlorophenyl) -5-isothiocyanatomethyl-2-isoxazoline

By reacting 19 g of OC ^ dichlorobenzaldoxime with 15 g Allyl isothiocyanate, 9.5 g of the title compound are obtained in the form of an oily liquid.

Analysis: CHNS

calculated: 52.28% 3.59 11.08 12.69 found: 52.56% 3.37 10.85 12.97

Example 9 3- (3-Chlorophenyl) -S-isothiocyanatomethyl ^ -isoxazoline

By reacting 40 g of CX, 3-dichlorobenzaldoxime with 10 g Allyl isothiocyanate, 6 g of the title compound are obtained in the form of an oily liquid.

Analysis: C H N Cl S

Calculated: 52.28% 3.59 11.08 14.02 12.69 found: 52.43% 3.72 10.87 14.98 12.58

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"Ti" 272670 J.

Example 10 S-Isothiocyanatomethyl ^ - (4-nitrophenyl) -2-isoxa2oline

12.5 g of 4-nitrobenzaldehyde are converted into the chlorinated one Oxime and then sets the compound obtained in this way with 15g Allyl isothiocyanate. In this way, 1 g of the title compound, which melts at 136 ° to 138 ° C., is obtained.

Analysis: CHNS

calculated: 50.18% 3.45 15.96 12.18

found: 50.47% 3.52 15.69 11.98

Example 11

S-isothiocyanatomethyl-S- (4-trifluoromethy! Phenyl) -2-isoxa-

zolin

175 g of 4-trifluoromethyl benzaldehyde are converted into the chlorinated Cxiin, through its subsequent implementation with 200 g Allyl isothiocyanate, 199 g of the title compound are obtained, which melts at 124 to 126.degree.

Analysis: CHNS

calculated: 50.35% 3.17 9.79 11.20 found: 50.55% 3.27 9.54 11.23

Example 12 3- (2,6-dichlorophenyl) -S-isothiocyanatomethyl - ^ - isoxazoline

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2 7 2 b 7 b J

35 g of 2,6-dichlorobenzaldoxiro are chlorinated in the manner described Way on the OC carbon atom and continues the so-made Then compound with 25 g of allyl isothiocyanate. In this way, 7 g of the title compound are obtained melts up to 66 ° C.

Analysis: 46 C. 2 H 9 N 1 1 S. calculated: 45 .01% 2 / 81 9 , 76 1 1 , 17th found: , 82% , 80 , 97 , 01

Example 13

3- (3-chloro-4-ir.ethoxyphenyl) -5-isothiocyanate omethy 1-2-

-isoxazoline

Example 14 5-Isothiocyanatomethyl-3- (4-methoxyphenyl) -2-isoxazoline

28 g of 4-methoxybenzaldoxime are first chlorinated and set the compound obtained in this way then with 25 g of allyl isothiocyanate, as described in Example 1 to. By chromatographic work-up of the product mixture obtained 9 g of 3- (3-chloro-4-methoxyphenyl) -5- isothiocyanatomethyl-2-isoxazoline (melting point 92 to 94 ° C) are obtained and 90 mg of 5-isothiocyanatomethyl 1-3- (4-methoxyphenyl) -2-isoxazoline (oily liquid).

(Example 13) Analysis: CHNS

calculated: 50.98% 3.92 9.91 11.3-1 found: 51.25% 4.00 9.67 11.33

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(Example 14) Analysis: CHNS

calculated: 46.01% 2.81 9.76 11.17 found: 46.24% 2.72 9.85 11.06

Example 15 S-Isothiocyanatomethyl-β- (4-irethy! Phenyl) -2-isoxazoline

29 g of 4-methylbenzaldoxime are chlorinated accordingly and set the compound thus prepared then with 25 g of allyl isothiocyanate. In this way you get 4.1 g of the title compound, which melts at 80.5 to 81 ° C.

Analysis: CHNS

calculated: 62.04% 5.21 12.06 13.80 found: 61.76% 5.18 11.9 (. 14.05

Example 16 3- (4-Bromophenyl ) -5 -isothiocyanatomethyl-2-isoxazoline

10 g of 4-bromobenzaldoxime are chlorinated accordingly and set the compound obtained in this way then with 10 g of allyl isothiocyanate. In this way one arrives at 15 g of the title compound, which melts at 123 to 125 ° C.

Analysis: CHNS

calculated: 44.46? 3.05 9.43 10.79 found: 44.21? 3.15 9.20 10.8O

7 0 9 H i> 1/0 9 7 6

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Example 17
3- (4-fluorophenyl) -5-isothiocyanatomethyl-2-isoxazoline

12.5 g of 4-fluorobenzaldoxime are chlorinated accordingly and
then reacts the compound obtained with 50 ml of allyl isothiocyanate. In this way, 3.4 g of the title compound, which melts at 59 to 61 ° C., are obtained.

Analysis: CHNS

calculated: 55.92% 3.84 11.86 13.59 found: 56.08% 3.95 12.25 13.92

Example 18 3- (2-Isopropy! Phenyl) -S-isothiocyanatomethyl-1-isoxazoline

1 g of 2-isopropybenzaldehyde is converted into the oxime and chlorinated, whereupon the compound thus obtained is reacted with 20 g of allyl isothiocyanate. This is how you get to 100 mg of the title compound in the form of an oily liquid.

Analysis: CHNS

calculated: 64.59% 6.19 10.76 12.32 found: 64.36% 5.92 10.43 12.62

Example 19 3- (4-1sopropy! Phenyl) -5-isothiocyanatomethyl-2-isoxazole n

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272b7t> 3

15 g of 4-isopropybenzaldehyde are converted into the oxime, the it is then chlorinated and subsequently reacted with 20 g of allyl isothiocyanate. In this way you get 2 g of the title compound, which melts at 68 to 70 ° C.

Analysis: 64 C. 6th H N 76 1 2 S. calculated: 64 .59% 6th / 19th 10, 45 1 2 / 32 found: .31% , 00 10, / 38

Example 20 S-Isothiocyanatomethyl-S- (2-pyridyl) -2-isoxazoline

12 g of 2-pyridinaldoxime are chlorinated accordingly and set the compound thus obtained then with 25 ml of allyl isothiocyanate. In this way, 14 g of the title compound are obtained in the form of a liquid.

Analysis: CHN

calculated: 54.78% 4.14 19.16 found: 54.70% 4.09 18.94

Example 21 5-Isothiocyanatomethyl-3- (4-pheny! Phenyl) -2-isoxazoline

17 g of 4-phenybenzaldehyde are converted into the corresponding one Oxime, which is then chlorinated and subsequently reacted with 25 ml of allyl isothiocyanate. In this way you get 6 g of the Title compound melting at 162-164 ° C.

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Analysis: 69 C. 4th H 9 N 10 S. calculated: 69 .36% 4th , 79 9 , 52 11 , 89 found: , 65% , 75 , 39 , 11

Example 22

3- / 3-chloro-4-hydroxy-5- (tert-butyl) phenyl / -5-isothiocyanato-

methyl-2-isoxazoline

25 g of 4-hydroxy-3,5-bis (tert-butyl) benzaldoxime are chlorinated according to the process described in Example 1, whereby 1 g of <* _/ 3-dichloro-4- -hydroxy-5- is obtained by chlorination and rearrangement (tert-butyl) benzaldoxime is obtained. Subsequent reaction of this intermediate with an excess of allyl isothiocyanate gives 1 g of the title compound in the form of an oily liquid. NM3 spectrum: singlets at 1.41 and 6.18 ppm, multiplets at 2.92-3.93, 4.68-5.23 and 7.5-7.63 ppm.

Example 23 5-Isothiocyanatomethyl 1-3,4-diphenyl-2-isoxazoline

By reacting 3.5 g of cinnamyl isothiocyanate with 5 g of OL- chlorobenzaldoxime by the method described in Example 1, 1 g of the title compound is obtained, which melts at 94 to 96.degree. NMR multiplets at 3.62-4.12, 5.65-5.78 and 7.22-7.83 ppm.

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Example 24

3- (3-chloro-4-benzyloxyphenyl) -5-isothiocyanatomethyl-2

-isoxazoline

Example 25

3- (3,5-dichloro-4-benzyloxyphenyl) -S-isothiocyanatomethyl ^ -

-isoxazoline

21 g of 4-benzyloxybenzaldehyde are converted into the oxime and chlorinated. This gives two chlorinated products, namely CX _/ 3-dichloro-4-benzyloxybenzaldoxime and (X, 3,5-trichloro-4-benzyloxybenzaldoxime. Reacting this intermediate product mixture with 20 g of allyl isothiocyanate gives 5.4 g of 3- (3 -Chloro-4-benzyloxyphenyl) -5-isothiocyanatomethyl- -2-isoxazoline and 1.38 g of 3- (3,5-dichloro-4-benzyloxyphenyl) - -S-isothiocyanatomethyl-isoxazoline Liquids and have the following NMR spectra:

Example 24

Nuclear Magnetic Resonance Spectrum: 2.83-3.82, 4.63-5.20, 5.17, 6.96, 7.25-7.78 ppm.

Example 25

Nuclear Magnetic Resonance Spectrum: 2.77-3.83, 4.60-5.28, 5.05, 7.20-7.78 ppm.

The following example shows the synthesis of those compounds of the formula I which have a nitrile substituent.

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Mon

Example 26 5-Cyanomethyl-3-phenyl-2-isoxazoline

60 g of benzaldoxime are chlorinated in chloroform at one temperature of 10 C using dry gaseous chlorine, whereupon the resulting reaction mixture to dryness evaporates. The residue is taken up in a mixture of tetrahydrofuran and ether and 100 g are then added to the whole Allyl cyanide. The reaction mixture is then heated to 10 ° C cooled and treated dropwise with 100 g of triethylamine, the temperature always being kept below 20 ° C. The mixture is stirred overnight. A large amount of water is then added and the organic layer is separated off. The water layer is extracted with diethyl ether, and the ether layer is combined with the organic layer of the reaction mixture. The combined organic layers are evaporated to give a viscous oil. By crystallizing this oil from chloroform leads to 62 g of 5-cyanomethyl-3-phenyl-2-isoxazoline, which melts at 79 to 80.5 ° C.

Analysis: CHN

calculated: 70.95% 5.41 15.04 found: 70.56% 5.55 14.77

The following examples show the synthesis of typical thioureas of formula I.

Example 27

A- / JJ3- (4-chlorophenyl) -2-isoxazoline-5

carbazld

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25 g of the product from Example 1 are placed in 200 ml with excess hydrazine over a period of 2 hours Around ethanol, the reaction mixture being allowed to come to reflux temperature. The precipitating after cooling Solids are filtered off, yielding 27 g of the title compound which melts at 115-117 ° C. NMR singlets at 4.48, 7.4, 7.63, 7.97 and 8.73 ppm and multiplets at 3.05-4.12 and 4.67-5.28 ppm.

Example 28

1,1-diisopropyl-3-ZZ3- (4-methylphenyl-2-isoxazolln-5-ylZmethylZ-

thiourea

5 g of the product from Example 15 are reacted with excess diisopropylamine at room temperature for 7 days. That included The reaction mixture obtained is then chromatographed over a 12 m high silica gel column using methyl ethyl ketone as an eluent. The desired product is in the first fraction out of the column. By evaporating the Solvent, 1 g of 1,1-diisopropyl-S-ZZS- (4- -methylphenyl ^ -isoxazolin-S-yVmethyl / thiourea in the form an oily liquid. NMR singlets at 2.37, 5.82, 7.15 and 7.52 ppm and multiplets at 1.15-1.37, 2.87-3.72, 3.98-4.2 and 4.37-5.25 ppm.

Example 29

N-Z / 3- (3-trifluoromethylphenyl) -2-isoxazolin-5-ylZmethy] y-4-

-morpholine thiocarboxamide

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100 mg of the product from Example 5 are reacted with excess morpholine, giving 100 mg of the title compound, which melts at 118 to 120.degree.

Analysis: CHNS

calculated: 51 .47% 4th , 83 11 , 26 8th , 58 found: 51 , 54% 4th , 44 11 , 03 8th , 41

Example 30

N- / 2- (3-phenyl-2-isoxazolin-5-yl) ethyV-4-morpholinthio-

carboxamide

100 mg of the product from Example 2 are reacted with excess morpholine to give 100 mg of the title compound
which melts at 128 to 130 ° C.

Analysis: CHNOS

calculated: 60.19% 6.58 13.17 10.03 10.03 found: 60.19% 5.30 12.97 11.09 10.07

Example 31

- (4-chlorophenyl) -2-isoxazolln-5-y ^ / methyl / -3-methyl-

thiourea

3 g of the product from Example 1 are mixed with 5 ml of 40% strength methylamine in aqueous ethanol. The mixture is left for 1 hour

709851/0976

stir, whereupon it is left to stand overnight. The unusual one Product is collected and recrystallized from methanol / water. By recrystallizing a second time from chloroform one arrives at 0.8 g of the title compound, which melts at up to 133.degree.

Analysis: C. 79% 4th H N 81 Cl 49 11 S. calculated: 50, 92% 4th / 97 14, 68 12, 74 11 , 30 found: 50, , 86 14, 12, / 29

Example 32 S-methoxycarbonylamino-methyl-S-phenyl-1-isoxazoline

24 g of benzaldoxime are chlorinated accordingly, whereupon the the material obtained is separated off and dissolved in diethyl ether. The solution is cooled to 15 ° C. and added with 46 g of methyl allyl carbamate offset. 60 ml of triethylamine are then added dropwise to this solution, the temperature being maintained at keeps below 20 ° C. The reaction mixture is first stirred for 3 hours and then filtered. The filtrate becomes dry evaporated, whereupon the residue is washed with water and the whole is filtered again. This is how you get to 32 g of the title compound, which melts at 102-103 ° C. NMR singlets at 3.63 and 5.48 ppm, multiplets at 2.82-3.80, 4.57-5.08, 7.13-7.50 and 7.45-7.77 ppm.

The following example shows the preparation of amino compounds of formula I.

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Example 33 5-Airdnomethyl-3-phenyl-2-isoxazoline

5 g of the product from Example 32 are slurried in 50% aqueous hydrochloric acid and the whole is heated then at reflux temperature overnight. The mixture is then cooled, neutralized with potassium hydroxide and extracted with chloroform. The chloroform layer is concentrated to 10 ml, whereupon the whole thing is reduced to a height of 12 m are filled with polystyrene gel beads column, which is eluted with chloroform. The desired product is in the second fraction coming out of the column. In this way, 2 g of 5-aminomethyl-3-phenyl-2-isoxazoline are obtained in Form of an oily liquid. NMR multiplets at 2.57-3.83, 4.43-4.98, 7.08-7.60 and 7.42-7.80 ppm and a singlet at 1.38 ppm.

The next example shows the preparation of the thiadiazoles of formula I.

Example 34

N - // 3- (4-chlorophenyl) -2-isoxazolin-5-y! ./ methyl./-N- (5-methy 1- -1,3,4-thiadiazol-2-yl) acetamide

5 g of the product from Example 27 are treated at the reflux temperature with 100 ml of acetic anhydride and 50 ml of acetyl chloride in 100 ml of dioxane until the mixture becomes clear. Afterward the reaction mixture is evaporated under vacuum to form a viscous sludge. The sludge is mixed with 50 ml of chloroform

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added and the mixture filtered. The filtrate is evaporated to dryness and the material obtained is in Dissolved 25 ml of concentrated sulfuric acid, whereupon the whole thing is stirred overnight at room temperature. The acid suspension is then poured into water, and subsequent filtration of the aqueous suspension yields 5 g of N- - // 3- (4-chlorophenyl) ^ -isoxazolin-S-yl. / Methyiy-N- (5-methyl- -1,3,4-thiadiazol-2-yl) acetamide, which at 195 to 197 ° C melts. NMR singlets at 2.43, 2.63, 7.55 and 7.78 ppm, as well as multiplets at 3.00-3.92, 4.23-4.53 and 4.88-5.50 ppm.

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To determine their ability to protect plants from the adverse effects of fungal leaf phytopathogens the compounds of the formula I given above are examined accordingly. The following examples show the investigations used for this purpose as well as those using typical compounds according to the invention obtained results.

For most investigations, the respective compound is formulated by dissolving or suspending about 3.5% by weight Active ingredient in a 5O: 5O mixture of acetone and ethanol, which on 100 ml contains approximately 10 g of a non-ionic surfactant. The solution is then deionized in such an amount Water dispersed that you get water dispersions with the different concentrations of active ingredient, as they are given in the following individual examination methods and in the respective tables. The concentrations will be each measured in parts per million parts by weight (ppm).

The active ingredient dispersions obtained in this way are in most examinations using an air atomizer on the plants to be examined in such Sprayed amount so that the plants are thoroughly wetted. For some investigations, other formulations and Application methods used as described below.

Untreated infected controls and untreated normal controls are also used in each examination. The results obtained from these examinations are rated on a rating scale from 1 to 5, where the number 1 stands for a serious illness and the number 5 a complete fight against the disease

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Hi

referred to as. A space in the respective table shows / that the compound mentioned in the specified Concentration has not been investigated. In some cases, a particular phytopathogen is examined several times, and the test values given for this then represent mean values. The ones used for these investigations Connections are identified by the number of the examples associated with them.

Test method 1 dry rot in tomatoes

4-week-old tomato seedlings are sprayed with aqueous dispersions of the compounds to be tested, each contain the amounts of active ingredient shown in Table I below. The next day you vaccinate the foliage of these plants with an aqueous suspension of offshoots of Phytophthora infestans. The inoculum has been grown on infected wheat seeds. The plants are then kept in a damp room for 2 days, after which you put them in the greenhouse. About 1 week after application of the active ingredient, the plants are observed and the results obtained Disease control assessed.

Investigation method 2 Powder melt dew in beans

Ten-day-old bean seedlings are used as host plants. The foliage of these bean plants is sprayed then with aqueous dispersions which contain the active ingredients shown in Table I below in the specified Contain concentrations, whereupon the whole thing is left to dry, the plants are placed in a greenhouse and

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27257b3 Ί?

finally inoculating by placing them between other bean plants, that are heavily infested with powder meltau (Erysiphe polygoni). After about 10 days, the Plants examined, the results obtained thereby being recorded in the usual way.

Investigation method 3 Anthracnose in cucumbers

Aqueous dispersions with the active compound concentrations given in Table I below are reduced to healthy Cucumber seedlings are applied that grow in sterile greenhouse soil. The following day the plants are with Inoculated conidia of Colletotrichum lagenarium in the form of an aqueous suspension. The fungus is on potato dextrose agar grown in petri dishes. The plants will then placed in a damp room for 2 days and then brought into the greenhouse. About 12 days after the treatment the clinical picture is examined and evaluated with the active ingredient.

Investigation method 4 rice brandy

Dispersions of the active ingredients to be examined in each case with the concentrations given in the table below are grown on healthy rice seedlings that grow densely in plastic pots applied. On the following day, the plants are inoculated with Piricularia oryzae (on rice husk agar grown) and then put them in a humid room for 2 days. The plants are then placed in the greenhouse for 5 to 7 days then examines them.

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27257b »

Examination method 5 Helmlnthosporium leaf spots in ways

Healthy wheat airs are planted in sterile greenhouse soil. As soon as the seed plants are 10 to 13 cm high, they are sprayed with dispersions of the active substances to be investigated, which contain the active compound concentrations given in Table I below. Inoculated the day after treatment one the plants with a suspension of on potato dextrose agar cultured spores of Helminthosporium sativum. The plants are then placed in a damp room for 2 days, so that the pathogen begins to grow, and then brought into the greenhouse. 1 week after Treatment, the plants are examined and the results obtained are noted accordingly.

Investigation method 6 wine botrytls

Healthy grapes are sterilized by immersion in dilute sodium hypochlorite solution and washed thoroughly. The berries are placed on sieve racks in divided Pyrex plates. Then the berries are flamed and sprayed with dispersions of the particular compound to be investigated. The next day the berries are by spraying 5 ml of a conidia suspension of Botrytis cinerea onto the plates each containing 12 berries inoculates. The inoculum was grown on frozen lima bean agar. After adding a small amount of water each plate is provided with a cover. The whole is left for 48 hours at a temperature of 25 ° C, whereupon the berries are examined and the disease infestation assessment is made.

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investigation method 7 apple scab

Apple seedlings with 4 to 6 leaves are sprayed with aqueous dispersions of the compounds to be examined. At the the following day the plants are sprayed with a suspension of fresh conidia of Venturia inaequalis. the The conidia used come from infected apple seedlings, which serve as a source for obtaining inoculum. The plants are then kept in a humid room at a temperature of 20 ° C. for 2 days to prevent disease development to set in motion, after which they are brought into the greenhouse. About 2 weeks after the application of the active ingredient, the Examined plants and noted the results obtained.

Investigation method 8 Downy mildew in grapevines

Young developing leaves are removed from healthy grapevines on the day of the experiment. You will be individually with the Bottom facing up on a spread out plastic fiber mat placed in plastic petri dishes. Water is added to each of the Petri dishes and each petiole is taken with it wrapped in a cotton ball soaked with water. Each individual leaf is then sprayed with an aqueous dispersion the connection to be examined in each case.

After the active ingredient dispersions have dried, the leaves are inoculated by applying a Conidia suspension of Plasmopara viticola (on infected

Leaf tissue grown) sprayed. Then you cover the bowls and leave them at a temperature of about 18 ° C

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and 100% relative humidity, keeping them under artificial lighting for 8 hours a day. To
about 1 week all leaves are examined and evaluated
any disease symbols that have occurred.

Examination IP method 9 Cercospora leaf spots on sugar beets

Sugar beet seedlings are transplanted into square plastic pots and allowed to grow in them for 3 weeks. Afterward
one sprayed the leaf surfaces of the obtained in this way
Plants with aqueous dispersions which contain 400 ppm of the particular compound to be examined. After drying
of the dispersions, but within 24 hours, the plants are inoculated with a conidia suspension of Cercospora
beticola. The organism was grown on a sugar beet leaf agar. The plants are then kept in a moist room for 2 days, after which they are placed in the greenhouse and examined 2 to 3 weeks later.

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Table I.

link

from example order no. amount ppm

cn 2

3 4 5

400 4th 80 4th 16 2 3.2 1 400 100 25th 400 400 1 400 1 100 25th

Late

Dry Powder Anthrac Rice Helmlntho Apple Fluff Cercos

rot meltau nose brand sporium botrytis scab meltau para

1
4th

nose

2
1

1 1 2 1

4th 4th INTO THE
-3 ι 4th
1 4 ir,
4th cn σ 1 1 * "** ■ ι 1 U) 5 4th

Table I (continued) Connection Late

from example
No. Assignment-
amount ppm Dry
rot Powder-
meltau Anthrac
nose rice
fire Helmintho-
sporium 1 Botrytis Apple
scab Fluff-
meltau Oercos
pora 6th 400 1 1 2 1 2 3 1 1 4th 1 100 1 4th 25th 3 6th 3 · * »
O 7th 400 1 1 1 3 1 1 2 1 9851 / 100
25th 1
1 1
1 O
CO 8th 400 1 1 3 1 o> 9 400 1 2 1 1 1 4th 1 10 400 1 1 1 4th 4th 1 4th 100 3 4th 25th 1 1

■ - j - *

CJ5, OO

Table I (continued)

Connection late

of example order- dry powder- anthrac- rice- helminthe- apple- fluff- cercos-

No. amount ppm rotten meltau nose brand sporium Botrytis sharp meltau para

11 400 1 1 1 100

25th

12 400 1 1 1

O 100 3

oo 25 1

^ 13 400 1 1 1 1

2 100

σ> 25

14 400 111

fire sporium 2 4th 4th 3 4th 1

5 4th 5 3 5 1 5 1 4th 1 5 2 1 1 1 1

Table I (continued) Connection late

vcn example order- dry powder- anthrac- rice- helminthe- apple- fluff- ceroos-

l l bd

No. amount ppm lazy meltau nose fire sporium Botrytis scab meltau pora K) 15th 400 1 1 3 3 3 1 3 5 2 100 1 3 1 1 1 25th 1 1 1 1 1 16 400 1 1 1 3 1 5 1 • J
O 17th 400 1 1 1 2 1 4th 4th 1 9851 / 18th
19th 400
400 1 1
3 1
1 1
4th 1
1 1
1 5 1 ο
CD 20th 400 1 1 1 1 1 5 4th 1 - «J
β » 21 400 1 1 2 1 1 1 1 1 1 22nd 400 1 1 1 1 5 1 23 40O 1 1 1 1 5 5 24 400 1 1 1 1 4th 4th 25th 400 1 1 1 1 4th 4th 26th 400 1 1 1 1 1 1 1 1

Table I (continued)

Compound Late by Sample Order- Dry- Powder- Anthrac- Rice- Helmlntho- Apple- Fluff- Cercos-

No. amount of ppn lazy meltau nose fire savings Botrytis scab meltau pora (J7 27 400 1 1 1 1 1 1 1 1 1 28 400 1 1 1 1 1 1 1 1 29 400 1 1 1 1 1 1 1 1 30th 400 1 1 1 1 1 1 1 1 «Α
ο 31 400 1 1 1 1 co 00 32 400 1 1 1 1 1 1 4th 1 2 cn - * 100 1 1 -j κ; ι ο
co 25th 1 1 ** J ^ 45. α> 33 400 1 1 1 1 1 1 1 1 4th 100 1 25th 1 34 400 1 1 1 1 1 1 1 1 1

-AIBT-

2 7 2 b 7 b

A number of compounds according to the invention are also corresponding Subjected to special investigations regarding their effect on downy mildew and botrytis on grapes. The investigation methods used for this purpose correspond to the methods described above, but with the different ones Multiple examinations can be carried out in each case. The investigations listed below were repeated several times in a number of cases and the results obtained are therefore averaged.

Table II

link
from Bei
game no. assignment
amount ppm fluff
meltau Botrytis 1 800 5 1 4OO 5 2 200 5 1 100 4th 50 4th 25th 3 12.5 2 2 800 5 4th 400 4th 3 2 00 4th 1 100 1 3 800 1 4 00 5 1

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Table II (continued)

link
from Bei
game no. assignment
amount ppm fluff
meltau Botrytis 3 200 4th 1 100 4th 50 4th 25th 3 4th 400 1 200 1 2 100 1 2 50 2 1 5 800 5 2 400 5 1 200 5 1 100 1 6th 400 5 2 200 5 2 100 4th 1 50 4th 1 7th 800 5 1 400 5 1 200 4th 1 100 1 50 1

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^S * 27257b3

Table II (continued)

link
from Bei
game no. assignment
amount ppm fluff
meltau Botrytis 8th 400 5 200 1 100 2 50 2 9 400 5 200 2 100 1 50 1 10 800 1 400 4th 1 200 2 1 100 3 1 50 2 1 11 800 1 400 5 1 200 5 1 100 4th 1 50 4th 1 25th 5 12th 800 5 3 4OO 5 1 200 4th 1

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Table II (continued)

link
from Bei
game no. Assignment-
amount ppm Fluff-
meltau Botrytis 12th 100 4th 50 4th 25th 1 13th 800 5 2 400
200
100 5
5
4th 2
2 50 3 25th 3 14th 800 5 1 400
200
100 U) Ut Ul 1
1 50 3 15th 800 5 3 400 5 4th 200 5 1 100 5 50 4th 25th 2 19th 800 1 400 5 1 200 5 1 100 5

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Tabel G-/
II (continued) Botrytis link
from Bei
game no. assignment
amount ppm fluff
meltau 19th 5O 3 25th 4th 12.5 1 20th 800 5 400 4th 200 4th 100 4th 50 4th 25th 1 21 800 5 400 4th 200 4th 100 4th 50 1 25th 1 1 26th 800 4th 1 400 3 1 200 2 1 27 800 4th 1 400 4th 1 200 3

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Tabel ta. Botrytis assignment
amount ppm link
from Bei
game no. 100 II (continued) 27 5O Fluff-
meltau 25th 2 1 800 3 1 28 400 1 1 200 4th 1 800 3 1 29 400 4th 1 200 5 1 800 5 1 30th 400 3 1 200 3 400 4th 31 200 2 100 5 50 3 1 800 1 1 32 400 2 1 200 4th 1 800 2 1 33 400 2 1 200 5 5 4th

272SV63

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Table II (continued)

link
from Bei
game no. assignment
amount ppm fluff
meltau Botrytis 33 100 2 50 2 25th 2 34 800 4th 1 400 4th 2 200 3 1

The compound of Example 1 is also tested on grapes growing in the field which are heavily affected by downy mildew are infested. The compound is used for this in the form of aqueous suspensions with active ingredient concentrations of 600 and 1200 ppm from a wettable powder formulation. To use it, spray the area in question throughout the season for downy dew at intervals of 7 to 10 days. Are the grapes under one extremely strong disease pressure, with the corresponding untreated control plants attacking 82% of the disease are, then results in the treatment with an active ingredient concentration 46% control of 600 ppm and treatment with an active ingredient concentration of 1200 ppm 87% control.

The most important property of the present compounds is their effectiveness against fungal leaf phytopathogens, but these compounds also have other interesting properties. If one examines typical

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2 7 2 b 7 b 3

inventive compounds in a system in which their Ability to inhibit the growth of microorganisms can be determined in vitro, then one arrives at the from the Results shown later in Table III. For these investigations, those described in more detail below are used Microorganisms grown in culture media suitable for the growth of these various organisms, which contain the compounds to be examined in different concentrations (micrograms per milliliter). In the later following Table III the lowest concentration is given in which the respective compound the Inhibits the growth of the specified microorganism.

A. Staphylococcus aureus 3055

B. Staphylococcus aureus 3074

C. Klebsiella pneumoniae KL14

D. Streptococcus faecalis X66

E. Proteus morganii PR15

F. Salmonella typhosa SA12

G. Bordetella bronchiseptica H. Escherichia coli EC14

I. Pasteurella multocida '(beef)

J. Pasteurella multocida (bird)

K. Mycoplasma gallisepticum 38502

L. Mycoplasma synoviae

M. Mycoplasma hyorhinis

N. Mycoplasma hyopneumoniae

0. Pseudomonas sp.

P. Aeromonas liquefaciens

Q. Erwinia amylovora

R. Candida tropicalis A17

S. Trichophyton mentagrophytes

T. Aspergillus flavus

U. Ceratocystis ulmi

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inding of
game no. A. B C 100 D. E. P. Tabel III 2 .10 <10 100 100 100 Microorga η i sine verD
By S 3 <1O <1O 100 100 100 100 GHI J 5 <10 <10 6th <1O 100 6 12 8th <1O <10 100 100 100 9
10 <no
100 100
100 100 11 <1O 100 <10 7098 12th
13th
14th <1O
<10
<10 <10
<1O 100
100 100 16 <1O / 0978 17th <1O 100 100 100 100 <10
«<10 18th <10 <10 19th <10 <10 100 100 20th 100 100 100 100 19th 21 32

K L M_ _N O P Q R S T U_

100 <10 <10 100 <Ί0 50 25 50 50 50 <10 <T1O <1O <10 <10

100 <10 <1O 100 <10

<10 <10 <1O <10 <10

100 <10 <10 100 <10 -Y

100 100 <10 100 <10 ir 100 100 100 ^σ

100

0.2

0.02 <10 <10 100 100 100

<10 100 <10 100 <10

<10 <10 100 <.1O 100 100 100 100 100

LJ I

- .5-4T -

Many compounds of the invention have also been found Proven to be effective against aquatic weeds. At concentrations of 10 ppm or less, the compounds are the Examples 2, 3, 5, 7, 8, 9, 12, 13, 14, 16, 17, 18, 19 and 20, for example, effective in combating bear's tail, Ceratophyllum demersum L., Hydrilla, Hydrilla verticillata, and water millet, Lemna minor L .. The compound of Example 9 was found to be effective in combating the above Aquatic weeds proven and in concentrations of only 2 ppm it is also effective for combating mermaid weeds, Najas marina L. and Cabomba, Cabomba caroliniana.

The data obtained in the above investigations show that with the compounds according to the invention protection of plants from the adverse effects of a number of fungal leaf phytopathogens. An important Aspect of the invention is therefore a new method for reducing the adverse effect of fungal leaf phytopathogens, that consists in treating the phytopathogens on the foliage of the host plants with an effective brings together phytopathogenhenunnen amount of a compound according to the invention. To carry out this procedure the respective compound according to the invention is applied to the plants to be protected.

In the above process, the phytopathogens treated with the active ingredient according to the invention do not necessarily have to be complete be killed. As the individual test values given above show, it already occurs when one is used sufficient amount of active ingredient to inhibit phytopathogens

709851/0978

to a reduction in the adverse effects of the respective disease, although this is only part of the Phytopathogen population is killed. Among phytopathogen inhibitors Amount is understood to mean that amount of active ingredient which leads to a reduction in the adverse effect of a phytopathogen is sufficient. The indication of a reduction in the adverse effect refers to one of these Weakening of the pathogen that causes it to reduce its reproductive speed and vitality comes. Compared to those growing on untreated plants As a result, phytopathogens only cause less disease and, at the same time, less damage to the Host plants.

As is customary in crop protection, you also get In the present case, the best results are obtained when the respective active ingredient is used several times at intervals during the growth period from 1 to a few weeks, depending on the weather and the severity of the disease.

The formulation of the compounds according to the invention and the preparation of corresponding dispersions from such formulations and the methods for applying such active ingredient formulations to the plants to be protected are carried out according to methods customary in the field of crop protection. Some explanations of the application methods are only used to spare the person skilled in the art corresponding own experiments.

When applying pesticides to the foliage of plants , the amount of active ingredient used is usually expressed by the concentration of the dispersion that is applied. The amount of active ingredient used is stated in this way because an amount of the dispersion which is sufficient to cover the foliage with a thin film is usually applied. The amount of active ingredient used is therefore dependent on the leaf surface of the plants to be treated, and the

ORIGINAL INSPECTED

the compound therefore depends on the respective concentration in the dispersion. Active ingredient concentrations in the range from about 50 to 1500 parts of active ingredient per million parts by weight of dispersion generally range according to the invention the end.

The compounds of the formula I according to the invention are usually used in the form of appropriate fungicidal agents, which are important embodiments of the invention. Such Agents contain a compound of the formula I and a phytologically acceptable inert carrier, and they often make concentrated formulations which are dispersed in water for their application, or dust formulations. The Production of such agents takes place according to processes and formulation techniques, as they are customary in agrochemistry, the main difference being in the presence of the Compounds of the formula I according to the invention consists. The following text refers to the appropriate fungicider Funds are taken to ensure that the agrochemist can readily obtain the desired fungicidal agent can produce.

The dispersions in which the active compounds according to the invention are applied to the foliage are mostly aqueous suspensions or emulsions which are produced from concentrated formulations of the respective active ingredients. Such water-suspendable or water-emulsifiable formulations are known as either wettable powders Solids or liquids known as emulsifiable concentrates. The wettable powders consist of one intimate mixture of the active ingredient, an inert carrier and surfactants. The active ingredient concentration is usually about 10 to 90 weight percent. Attapulgite clays, montmorillonite clays, diatomaceous earth are usually used as inert carriers or purified silicates are used. Effective top

709851/0976

surfactants comprising about 0.5 to 10% by weight of the wettable Powder are the sulfonated lignins, the condensed naphthalene sulfonates, the naphthalene sulfonates, the alkylbenzenesulfonates, the alkylsulfonates and the nonionic surface-active agents, such as adducts Xethylene oxide and alkylphenol.

Typical emulsifiable concentrates of the active ingredients according to the invention contain an active ingredient concentration of about 1ÖÖ to 500 g per liter of liquid, the active ingredient being dissolved in an inert carrier which is a mixture of one with water represents immiscible organic solvents and emulsifiers. Examples of suitable organic The solvents are the aromatics, especially the xylenes, and the petroleum fractions, especially the high-boiling ones naphthalene and olefinic fractions of petroleum, such as heavy aromatic naphtha. It can also be other organic Solvents are used, such as terpenic solvents including resin derivatives, and complex alcohols, like 2-ethoxyethanol. The same are suitable as emulsifying agents for the production of the emulsifiable concentrates surfactants such as those used to make wettable ones Powder can be used.

In order to improve the behavior of the aqueous dispersion for covering the foliage and a corresponding adhesion to it, appropriate adjuvants are often used. Examples of such auxiliaries are natural gums, emulsified Polybutenes, cationic surfactants, and lignin derivatives, and such agents often provide improvement of the respective application process.

709851/0976

The compounds according to the invention are less common applied in the form of dusts. Dusts of this type normally consist of the respective active ingredient in finely divided form Form dispersed in a powdered inert carrier. Powdered ones are mostly used as a carrier Clay, such as pyrophyllite, bentonite, volcanic deposits, or montmorillonite. Dusts of this type contain the respective Active ingredient usually in the highest possible concentration, for example in an amount of 1500 ppm or optionally even more than that.

Dispersions of the compounds according to the invention are in usually applied to the foliage of the plants to be treated. Low-pressure sprayers are suitable for this, High-pressure spray devices and low-volume air spray devices with which the water-dispersed active ingredients according to the invention let apply. Corresponding dust formulations are also used by conventional devices, through the the dust is blown with intimate contact onto the foliage of the plants to be treated.

709851/0978

Claims (1)

27257Ö3 Claims λ. _y Substituted isoxazolines of the formula I. R wherein 4 / V.3 for -NCS, cyano, amino, aminohydrohalide, -NHCSN (R ¹ R ² ), -NHCO ₂ (C ₁ -C ₃ alkyl) or a radical of the formula COCH ₃ ^N N - C - CH i . | (| ( - N stands, η stands for 1 or 2, 1 2 R and R independently of one another are hydrogen or C ^ -C ₃ Mean alkyl or 1 R is hydrogen and R is amino or 1 2 R and R together with the nitrogen atom to which they are attached are, form morpholino, piperidino or piperazino, R represents hydrogen or phenyl, R naphthyl, 2-pyridyl or a radical of the formula 5 I. is, 709851/0976 ORIGINAL INSPECTED 2 7 2 b 7 6 3 wherein the substituents R, R and R are independently chlorine, bromine, fluorine, nitro, trifluoromethyl, C ₁ -C ₂ alkoxy, C ₁ -C ₂ alkylthio, C ^ -C ₄ alkyl, hydroxy, phenyl, benzyloxy or hydrogen, with the proviso that at most one of the substituents R, R or R denotes phenyl or benzyloxy, and with the further provisos that (1) no more than one of the substituents R ⁵ , R ⁶ and R ^{7 represent} tert-butyl if one of the substituents R, R or R is hydroxy, alkoxy or benzyloxy, and that (2) if one of the substituents R, R or R is chlorine, the hydroxy, alkoxy or benzyloxy groups are then arranged in the ortho position to it. 2. Compound according to claim 1, characterized in that R represents hydrogen. 3. A compound according to claim 2, characterized in that
or -NHCO ₂ (C ₁ -C ₃ alkyl). indicates that R stands for -NCS, cyano, -NHCSN (R ¹ R ² ) 4. A compound according to claim 3, characterized in that R is -NCS, cyano or -NHCO ₂ (C ₁ -C ₃ alkyl). 709851/0976 5. A compound according to claim 4, characterized in that R stands for -NCS. 6. A compound according to claim 5, characterized in that g e - 4th
indicates that R is 2-pyridyl or a Remainder of the formula stands. 7. A compound according to claim 1, characterized in that R is -NCS, cyano, -NHCSN- (R ¹ R ² ) or -NHCO ₂ (C ₁ -C ₃ alkyl). 8. A compound according to claim 7, characterized in that R is -NCS, cyano or -NHCO- "(C ₁ -C ₃ alkyl]). 9. A compound according to claim 8, characterized in that R is -NCS. 10. A compound according to claim 9, characterized in that R is 2-pyridyl or one Remainder of the formula _J *. stands. R ⁵ 11. A compound according to claim 1, characterized in that - 4th
indicates that R is 2-pyridyl or a Remainder of the formula stands. 12. A compound according to claim 11, characterized that R is hydrogen. 709851/0978 13. A compound according to claim 12, characterized in that R is -NCS, cyano, -NHCSN- (R ¹ R ² ) or -NHCO ₂ (C ₁ -C ₃ alkyl). 14. A compound according to claim 13, characterized in that R is -NCS, cyano or -NHCO ₂ (C ₁ -C ₃ alkyl). 15. S-isothiocyanatomethyl-S- (2-pyridyl) -2-isoxazoline according to claims 1 to 14. 16. A compound according to claim 1 to 14, characterized 4 characterized in that R stands for a radical of the formula _ / "% j. 17. 5-Isothiocyanatomethyl 1-3- (4-chlorophenyl) -2 ~ ± soxazoline according to claim 16. 18. S-isothiocyanatomethyl-S- (4-trifluoromethylphenyl) -2- -isoxazoline according to claim 16. 19. 3- (2 _/ 6-dichlorophenyl) -5-isothiocyanatomethyl-2-isoxazoline according to claim 16. 20. S-isothiocyanatomethyl-S- (4-methylphenyl) -2-isoxazoline according to claim 16. 21. Fungicidal agent consisting of an active ingredient and a phytological one harmless inert carrier, characterized in that it is a compound as active ingredient the formula I mentioned in claim 1 contains. 709851/0976 ORlGfNAL INSPECTED 272b763 22. Composition according to claim 21, characterized in that it contains the active ingredient of formula I in one Contains concentration from 50 ppm to 90% by weight. 23. Means according to claim 21 in the form of a wettable powder, characterized in that it contains the active ingredient of the formula I in a concentration of 10 to 90% by weight. 24. Agent according to claim 21 in the form of an emulsifiable concentrate, characterized in that that it contains the active ingredient of the formula I in a concentration of 100 to 500 g per liter. 25. Composition according to claim 21 in the form of a dust, characterized in that it contains the active ingredient of formula I in a concentration of 50 to 1500 ppm. 26. Composition according to claim 21 to 25, characterized in that it is a compound as an active ingredient of formula I in which R is hydrogen. 27. Composition according to claim 26, characterized in that it is a compound of the active ingredient Formula I contains, wherein R -NHCO ₂ (C ₁ -C ₃ alkyl). Formula I contains where R is -NCS, cyano, -NHCSN (R ¹ R ² ) or 28. Composition according to claim 27, characterized in that it contains as active ingredient a compound of the formula I in which R is -NCS, cyano or -NHCO ₂ (C ₁ -C ₃ alkyl). 709851/0976 ORIGINAL INSPECTED 29. Composition according to claim 28, characterized in that it is a compound of the active ingredient Formula I contains where R is -NCS. 30. Means according to claim 29, characterized in that it is a compound of the active ingredient 4th
Formula I contains where R is 2-pyridyl or a radical of formula stands. 31. Composition according to claim 21 to 25, characterized in that it contains as active ingredient a compound of the formula I in which R is -NCS, cyano, -NHCSN- (R ¹ R ² ) or -NHCO ₂ (C ₁ -C ₃ Alkyl). 32. Composition according to claim 31, characterized in that it contains as active ingredient a compound of the formula I in which R is -NCS, cyano or -NHCO ₂ (C ₁ -C ₃ alkyl). 33. Composition according to claim 32, characterized in that it is a compound of the Formula I contains where R is -NCS. 34. Composition according to claim 33, characterized in that it is a compound of the active ingredient 4th
Formula I contains where R is 2-pyridyl or a radical of formula stands. 35. Composition according to claim 21 to 25, characterized in that it is a compound as active ingredient 4th
Preparation of the formula I contains, wherein R is 2-pyridyl or a 709851/0978 ORIGINAL INSPECTED Remainder of the formula stands. Means according to claim 35, characterized draws that it is a compound of the active ingredient Formula I contains in which R is hydrogen. Agent according to claim 36, characterized in that it contains as active ingredient a compound of the formula I in which R stands for -NCS, cyano, -NHCSN (R ¹ R ² ) or -NHCO ₂ (C ₁ -C ₃ alkyl). 38. Composition according to claim 37, characterized in that it contains as active ingredient a compound of the formula I in which R is -NCS, cyano or -NHCO- (C ₁ -C ₃ alkyl). 39. Means according to claim 27 to 30, 32 to 34 or 36 to 38, characterized in that it as an active ingredient of the formula I S-isothiocyanatomethyl-S- (2- -pyridyl) -2-isoxazoline. 40. Means according to claim 27 to 30, 32 to 34 or 36 to 38, characterized in that it contains as active ingredient a compound of the formula I in which R for a radical of the formula stands. 41. Composition according to claim 40, characterized in that it is 5-isothiocyanatomethyl-3- (4-chlorophenyl) -2-isoxazoline as the active ingredient of the formula I contains. 709851/0978 2 7 2 b 7 6 3 42. Composition according to claim 40, characterized in that it is 5-isothiocyanatomethyl-3- (4-trif1uormethylphenyl) -2-isoxazoline as the active ingredient of the formula I contains. 43. Composition according to claim 40, characterized in that it is 3- (2,6- -Dichlorpheny1) -5-isothiocyanatomethyl-2-isoxazoline contains. 44. Agent according to claim 40, characterized in that it is 5-isothiocyanatomethyl-3- (4-methylphenyl) -2-isoxazoline as the active ingredient of the formula I contains. 45. Use of the substituted isoxazolines of the formula I mentioned in claim 1 to reduce the disadvantageous Effects of fungal leaf phytopathogens, characterized that the phytopathogens on the foliage of the host plants can be treated with an effective phytopathogen inhibitor Amount of a compound of formula I treated. 46. Use according to claim 45, characterized in that the host plants are grapes. 47. Use according to claim 45, characterized in that the active ingredient of the formula I used in amounts of 50 to 1500 ppm. 48. Use according to claim 46, characterized in that the active ingredient of the formula I used in amounts of 50 to 1500 ppm. 709851/0976 27257b3 49. Use according to claim 45 to 48, characterized
characterized in that one works with an active ingredient of the formula I in which R is hydrogen. 50. Use according to claim 49, characterized in that one works with an active ingredient of the formula I in which R fi
or -NHCO ₂ (C ₁ -C ₃ alkyl). Formula I works, where R stands for -NCS, Cyano, -NHCSN (R ¹ R ² ) 51. Use according to claim 50, characterized in that one works with an active ingredient of the formula I in which R stands for -NCS, cyano or -NHCO ₂ (C ₁ alkyl). 52. Use according to claim 51, characterized that one works with an active ingredient of the formula I in which R stands for -NCS. 53. Use according to claim 52, characterized in that with an active ingredient the 4th
Formula I works in which R is 2-pyridyl or a radical . — Y of the formula j>% I. j> 54. Use according to claim 45 to 48, characterized in that one works with an active ingredient of the formula I in which R is -NCS, cyano, -NHCSN (R ¹ R ² ) or -NHCO ₂ (C ₁ -C ₃ alkyl ) stands. 55. Use according to claim 54, characterized in that with an active ingredient the Formula I works in which R stands for -NCS, cyano or alkyl). 709851/0978 56. Use according to claim 55, characterized that one works with an active ingredient of the formula I in which R stands for -NCS. 57. Use according to claim 56, characterized that one with an active ingredient the 4th
Formula I works in which R is 2-pyridyl or a radical the formula stands. 58. Use according to claim 45 to 48, characterized in that one with an active ingredient 4th
of formula I works in which R is 2-pyridyl or a radical the formula stands. 59. Use according to claim 58, characterized in that one works with an active ingredient of the formula I in which R ^{3 is} hydrogen. 60. Use according to claim 59, characterized in that one works with a compound of the formula I in which R is -NCS, cyano, -NHCSN (R ¹ R ² ) or -NHCO ₂ (C ₁ -C ₃ alkyl) . 61. Use according to claim 60, characterized in that one works with a compound of the formula I in which R is -NCS, cyano or -NHCO ₂ (C ₁ -C alkyl). 62. Use according to claim 50 to 53, 55 to 57 or to 61, characterized in that one works with 5-isothiocyanatomethyl-3- (2-pyridyl) -2-isoxazoline as active ingredient. 709851/0978 63. Use according to claim 50 to 53, 55 to 57 or to 61, characterized in that 4 you work with an active ingredient of the formula I in which R for is a radical of the formula -i / * ·. ft ^{7 v} 64. Use according to claim 63, characterized in that S-isothiocyanatomethyl-S- - (4-chlorophenyl) -2-isoxazoline works as an active ingredient. 65. Use according to claim 63, characterized in that S-isothiocyanatomethyl-S- - (4-trifluoromethylphenyl) -2-isoxazoline works as an active ingredient. 66. Use according to claim 63, characterized in that with 3- (2,6-dichlorophenyl) - -5-isothiocyanatomethyl-2-isoxazoline works as an active ingredient. 67. Use according to claim 63, characterized in that 5-isothiocyanatomethyl -3- (4-methy! Phenyl) -2-isoxazoline works as an active ingredient. 709851/0978