CH645513A5 - N-ARIL-N-ACIL-3-AMINO-OSSAZOLIDIN-2-ONI FUNGICIDES. - Google Patents

Description

The present invention relates to new fungicides and more particularly to new fungicides belonging to the class of 3-amino-oxazolidin-2-oni, having high fungicidal activity combined with good compatibility with the higher plants that must be defended against fungal attacks, and their use.

Fungicidal compounds belonging to the class of N-phenyl-1, 3-oxazolidin-2,4-dions have been described for example in the Dutch patent application n. 68/17249 (Sumito-mo), in the French patent no. 2 172 295 (BASF) and in the Italian patent application no. 20 579 A / 78 in the name of the same Applicant.

The bactericidal and fungicidal activity of some alanine and glycine derivatives bearing on the nitrogen atom a variously substituted phenyl and an acyl group of various nature has also recently been described. In particular, this acyl group can be constituted with an ao ß aloalkanoyl (German patent application DOS No. 2 513 789, Ciba Geigy), or by an acetyl group substituted in a with a sulfur or oxygen atom which is in turn bound to various groups (French patent application No. 7 510 722, Ciba Geigy) or from a 2-furoyl, 2-thenoyl or pyridyl-2-carbonyl group (German patent applications DOS No. 2 513 732 and 2 513 788, Ciba Geigy). The microbicidal activity of methylalanine-ti having a 2,6-dialkylphenyl and one of the following groups has also been described on the nitrogen atom: cyclopropanoyl, acryloyl, crotonoyl (Brev. Sviz. 593 612, 604 510).

Other fungicide acyl-aniline derivatives have recently been described in Belgian patent no. 863 615 (Ciba-Geigy) and s

I

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in the German patent application DOS 27 45 533 (Chevron).

The interest in the search for new derivatives of acylanilins with fungicidal action derives from the need to find in them a high fungicidal activity combined with a lack of phytotoxicity. In fact, some products already known, even if they have an excellent fungicidal action, are also toxic to the plants that you want to protect from fungal infections.

The damage caused by phytotoxicity to plants can hardly be avoided by using the dose of fungicidal compound which is the best compromise between the fungicidal activity of the compound and its phytotoxicity.

In fact, in the practical application in agriculture, the quantity of product that actually remains on the plant varies considerably in relation to various factors such as weather conditions (particularly the frequency of rains), the correctness and frequency of applications operated by the farmer.

Therefore it is necessary to have fungicide compounds with good fungicidal activity and a large safety margin so that even high doses of product do not cause damage to plants.

We have now found, and forms part of the present invention, that the compounds responding to the following general formula:

\

CH C = 0

I /

CH2 /

\ /

N

SA) -H

1

R

ir »which:

R, R1 and R2, equal or different from each other, = H, halogen,

alkyl CrC4, alkoxyl Cj-Cjj

R3 = H, CH3;

ch3 I

A = -CH3-; -CH-;

n = 0 or 1;

R4 = H, C alkyl, -CR optionally substituted with halogen atom, cycloalkyl C, -CR, C2-C- alkenyl ethinyl, halogen (when n = 1), CN, SCN, phenyl optionally substituted with CrC3 alkyls or atoms halogen, 5 or 6 term heterocyclic groups containing from 1 to 3 heteroatoms (in particular furile, tetrahydrofuryl, thienyl, pyrimidyl, pyridyl, imadazolyl, pyrazolyl, thiazolite); acetyl, COO-alkyl, -OR5, -SR5, -N-R5 [with R5 and R6 (equal or different from each other) = H,

Re alkyl Cj-Cg, alkenyl C2-C5, phenyl, heterocyclic group with 5 or 6 terms containing from 1 to 3 heteroatoms, S02-alkyl, acetyl] have high fungicidal activity and low phytotoxicity.

The use of the compounds of formula (I) in the fight against fungal infections in useful plants is therefore also the object of the present invention.

Only one of the compounds falling under the general formula (I) is known in the literature and more precisely the N-phenyl-N-acetyl-3-amino-oxazolidin-2-one compound of formula

(II)

CH

which was described in the publication J. of Organic Che-mistry 31, 968 (1966).

However, fungicide activity was not recognized for compound (ii).

Therefore, compounds of general formula I wherein at least one of R, R1, R2 and R3 is different from hydrogen when - (A) n-R4 = CHS form a further object of the present invention.

The preparation of the compounds of general formula (I) is carried out with processes known in the normal practice of organic chemistry.

For example, an arylhydrazine 3 can be prepared by reacting the corresponding aniline 1 with sodium nitrite (NaN02) in hydrochloric acid and then reducing the diazonium salt 2 thus obtained (Scheme 1, equation 1) as described for example in publication J . Am. Chem. Soc. 81, 4673 (1959).

The aryl hydrazine is then reacted with 2-haloethyl or 1-methyl-2-haloethyl chloroformate 4 (prepared in turn by the action of the phosgene on a halodrine) in the presence of a base, then the intermediate thus obtained is cyclized 5 in the presence of bases obtaining intermediate 6 (Scheme 1, equation 2). This process is described in J. Am. Chem. Soc. 48, 1951 (1926).

The intermediate 6 is then condensed with the appropriate acyl halide 7 according to the known techniques (Scheme 1, equation 3). The condensation reaction between the intermediate 6 and the acyl halide 7 can be replaced by analogous reactions known from the literature, which allow to introduce particular acyclic groups.

For example the compounds of general formula (I) wherein in the acyl part

R5

R4 = -OR5, -SR5, -NC!

R6

they can be prepared by reacting intermediate 6 with phosgene or with haloacetyl or halopropionyl halides (such as for example

C1-C-CH2C1 and C1-C-CH-CHS

II II I

OR OC1

respectively) and therefore replacing the halogen atom according to known techniques.

The compounds of formula (T) wherein the acyl part is

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4

-C-R4 and R4 = NHR5

II

OR

can be prepared by reacting the intermediate 6 with 5 an isocyanate of formula R5-N = C = 0.

The compounds of formula I wherein the acyl part is

-C-CH2-C-CH3 (A = CH2, R4 = acetyl)

II or o can be prepared by reacting intermediate 6 with dichetene.

Scheme 1

NH

N = rAu ©

NaNO / HCl

R

R (1)

Reducing c>

(2)

R

2) (3)

-HCl

+ Cl-C-O-CH-CH X

(5)

-Hx

R-hQ

(6)

3) (6) + X-G- (A) -R

n

THE

-Hx

(THE)

(X = halogen; R, R1, R2, R3, R4, A and n have the meanings reported in the general formula I).

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The compounds of general formula (I) are endowed with an excellent fungicidal activity against phytopathogenic fungi and their action has both a preventive character (i.e. preventing the onset of the disease) and a curative character (when the infection is already in progress).

They have good systematic characteristics (that is, they are transported to the various parts of the plant) so it is possible to apply them both by leaf and in the ground.

In addition, the compounds of general formula (I) are compatible with plants that need to be protected from fungal attack.

Most of the compounds of general formula (I) do not show any sign of phytotoxicity at the tested doses, the remaining ones have low phytotoxicity, lower than that of known fungicides.

The most important mushrooms from the point of view of the damage they cause to agricultural crops, which can be successfully combated through the products of formula I, are those belonging to the class of phycomycetes, such as Plasmopara spp, Phytophtora spp, Peronospora spp, Pseudoperonospora spp and Phythium spp.

The fungicidal compounds object of the invention are therefore useful for fighting fungal infections in useful plants such as for example vine, tobacco, tomato, potato and other horticultural crops.

In practical applications the compounds can be distributed in the area or on the plants to be protected, as such or in the form of suitable compositions consisting of one or more compounds of formula (I) as the active principle, of a solid or liquid carrier and possibly of surfactants and other additives.

If desired, other active ingredients such as other fungicides, insecticides, plant growth regulators etc. can be added to the compositions.

The compounds of the invention can be formulated according to conventional techniques, in dry and wettable powders, granular formulations, emulsifiable liquids, etc.

The quantity of formula I fungicide product to be used in the fight against phytopathogenic fungi depends on various factors such as the single compound used, the type of composition or formulation, the type and degree of infection, the type of cultivation to be protected, climatic factors and environmental etc.

In general, quantities between 10 and 500 g / ha are sufficient to ensure good protection of crops from fungal attacks, preferably between 100 and 250 g / ha.

With the aim of better illustrating the invention, the following examples are now provided.

Example 1

Preparation of N- (methoxyacetiì) -N-2- (2,6-dimethyl-3-ammi-nooxazolìdin-2-one

A) Preparation of 2,6-dimethylphenylhydrazine

107 g of 2,6-xylidine are added dropwise to a 200 ml solution of HCl concentrated in 150 ml of water.

After cooling to -5 ° C, a solution of 66 g of NaNOa in 150 ml of H2O is added to this mixture, under strong stirring, in a time of about one hour. To the yellow-orange suspension thus obtained, 450 g of SnCl2 are added at 0 ° C in about 4 hours. 2H20 in 600 ml of 5N aqueous solution of HCl.

It is kept under stirring for 24 hours, allowing the temperature to rise to + 20 ° C. The solid formed is filtered,

dissolved in 700 ml of H2Q at a temperature between 10 and 15 ° C, after which the product is extracted with diethyl ether (3 X 250 ml).

The ethereal extract, after washing with H2O and anhydrifying on Na? O? Is brought to a volume of 1500 ml with diethyl ether and treated with anhydrous gaseous HCl until complete precipitation of the 2,6-dimethylhydrazine hydrochloride.

The salt is filtered and dried, obtaining 40 g of white solid, having a melting point of 205-207 ° C with decomposition.

From hydrochloride, 2,6-dimethyl-pheneneIhydrazine is obtained by treatment with NaOH.

B) Preparation of 3- (2,6-dimethylaniline) oxazolidin-2-one

At 41.4 g of 2-bromoethylchloroformate, prepared from phosgene and ethylene bromhydrin, in 200 ml of benzene the following reagents are added at 10 ° C:

36.5 g of 2,6-dimethylphenylhydrazine (see A), and 18 g of pyridine in 100 ml of benzene.

After the addition, the temperature is left to rise to 20 ° C under strong stirring. Pyridine hydrochloride is removed by washing with water. The benzene solution is further washed with diluted HCl, with water up to neutral pH, dried on Na2SO4 and evaporated to give 61 g of an oily product which, crystallized from ligroi-na, provides 43 g of a clear solid, m.p. 58 ° -63 ° C, consisting of l- (2,6-dimethylphenyl) -2- (ß-bromoethyl) oxycarbonsIhydrazine.

[IR (Infrared Spectroscopy) v (C = 0): 1710 cm-1; v (NH-CO): 3180 cm-1; v (NH-Ar): 3340 cm-1 !.

40 g of this intermediate are dissolved in 500 ml of toluene and treated with 16 g of tetramethylguanidine. The mixture is heated under reflux for 3 hours under stirring.

After cooling it was washed with 200 ml of water then with 100 ml of diluted HCl and again with 200 ml of HaO.

The combined aqueous phases are extracted with CH, CL (2 X 200 ml).

The combined organic phases are dried over Na2SO4 and the solvent is evaporated to obtain a solid residue which is recrystallized from ligroin / ethyl acetate (2: 1). 22.5 g of 3- (2,6-dimethylaniline) -ossa-zolidin-2-one, m.p. are obtained. 107-110 ° C.

[IR: v (C = 0): 1770 cm "1; v (NH): 3340 cm" 1].

The cyclization reaction was repeated by dissolving the intermediate of m.p. 58-62 ° C in ethanol containing solid ethylate and reflux heating.

After a similar treatment of the reaction mixture, the same intermediate of m.p. was isolated 107-110 ° C.

C) 1.1 g of methoxyacetyl chloride are added to 2 g of the intermediate prepared as described in point B), in 70 ml of toluene and 0.2 ml of dimethylformamide. The reaction mixture is heated under reflux for 8 hours. After cooling, the reaction mixture is subjected to complete evaporation of the solvents.

The residue, consisting of 2.9 g of thick oil, is purified on a silica gel column, using a benzene / ethyl acetate (1: 1) mixture as the eluent.

Thus, after removing the solvents, 1.1 g of syrupy product are obtained which spontaneously crystallizes and which, after recrystallization of ligroin / ethyl acetate (1: 1); provides g 1 of the desired compound, the characteristics of which are shown in table 1 (compound n. 6).

[IR v (N-CO-CH2): 1680 cm "1; v (N-CO-O): 1780 cm" 1].

Example 2

By operating in a similar way to that described in Example 1, the compounds reported in the following Table 1 were prepared.

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TABLE 1 <*>

Compound n.

R

R1

R2

R3

n

TO

R4

mp <2> (° C)

IR (3) (cm-1)

1

h h

h h

1

chz cl

71-4

1690-1760

2

h h

h h

1

ch2

C6H5

112-4

1680-1760

3

h h

h

H

1

ch2

i • C3H,

oil

1680-1770

4

2-CH3

6-ch3,

H

H

1

CHZ

Cl

88-92

1635-1770

5

2-ch3

6-CHs

H

H

1

CH2

C6H5

oil

1670-1770

6

2-ch3

6-ch3

H

h

1

chjs och3

103-6

1680-1780

7

H

H

h

H

1

CH,

OCH3

86-91

1690-1760

8

2-CH3

6-ch3

H

H

1

CIL,

0-c0-ch3

oil

1690-1770

9

2-ch3

6-CH3.

H

H

1

ch2

Oh

135-8

1690-1770c4)

10

2-CH3.

6-CH3

H

H

-

co-OCH3

116-9

1680-1730-1790

11

2-CHs

6-ch3,

H

h

1

chjj

H

132-5

1670-1770

12

2-CHa

6-chj h

H

1

CH,

oc6h5

109-12

1690-1780

(1> The elementary analysis of each compound is consistent with the assigned structure.

<2> The melting points have not been corrected.

<3> Only the bands corresponding to v C = O are shown.

<4> v OH = 3530 cm-1.

Example 3

Curative activity on Downy mildew of the vine (Plasmopara viticola [B. et C.] Beri et de Toni)

The leaves of cv vine plants. Dolcetto, bred in pots in an environment conditioned at 25 ° C and 60% R.H., were sprayed on the underside with an aqueous suspension of Plasmopara viticola conidia (200,000 conidia / cc). After 24 hours of stay in an environment saturated with humidity at 21 ° C, the plants were treated by spraying on both the leaf pages with the products in question in 20% hydroacetonic solution of acetone (vol./vol.).

At the end of the incubation period (7 days), the severity of the infection was estimated at sight with indices of the following rating scale.

0: no check, infection equal to that of the witness

(infected and untreated plants)

1: 1-20% reduction in infection 2: 20-60% reduction in infection 3: 60-90% reduction in infection 4: reduction in infection greater than 90%.

The results obtained are shown in the following table 2.

TABLE 2

Curative activity for foliar application at a dose of 0.5% or on plants infected with Downy mildew of the vine

Compound n.

Activities

Compound n.

Activities

1

3

7

4

2

3

8

4

3

4

9

4

4

4

1G

4

5

4

11

4

6

4

12

4

Example 4

Curative activity on Downy mildew of tobacco 55 (Peronospora Tabacina Adam)

The leaves of cv tobacco plants. Burley, grown in pots in a conditioned environment, were sprayed on the underside with a suspension of conidia of Peronospora Tarn basin (200 000 conidia / cc).

After 6 hours of stay in an environment saturated with humidity, the plants were transported in a conditioned environment at 20 ° C and 70% R.H. for mushroom incubation. 24 hours after infection, the treatment was carried out by spraying both leaf pages with the product under consideration in a 20% acetone hydroacetonic solution (vol./ vol.).

At the end of the incubation period (6 days) it is

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Visually estimated the severity of the infection with indices of the same scale shown in example 3.

The results are shown in the following table 3.

TABLE 3

Curative activity for foliar application at a dose of 0.5% or on plants infected with Downy mildew of tobacco

TABLE 4 Phytotoxicity index at a dose of 0.6% o

Compound n.

Activities

4

4

6

4

Example 5 Determination of phytotoxicity

Vine leaves cv. Dolcetto bred in pots in an environment conditioned at 25 ° C and 60% R.H. they were treated by spraying both leaf pages with the products in question in a 20% acetone hydroacetonic solution (vol./vol.).

After 7 days, the severity of the phytotoxic symptoms was estimated on sight with indices of a rating scale ranging from 100 (completely damaged plant) to 0 (healthy plant).

The data are shown in the following table 4 in comparison with the phytotoxicity indices of 2 known compounds to be commercialized: «Furalaxyl» (English patent number 1 448 810 - Ciba Geigy) and «Ridomil» (French patent application No. 2 267 042 - Ciba Geigy).

Compound n.

Phytotoxicity index

1

0

3

10

4

0

6

0

«Furalaxyl» (1)

100

«Ridomil» (2)

60

«Furalaxyl» = N- (2,6-dimethylphenyl) -N- (r-carbomethoxyethyl) -2 - furoyl-amide

OR \

H C 3

-0-C

OR

CH

(2) "Ridomil" = N- (2,6-dimethylf enyl) -N (1 '-carbomethoxy-ethyl) -methoxyacetamide

H C 3

CH

C - CH,

Q

40

C - CH

CH

OCH

v

Claims (19)

645 513 2. Compounds according to claim 1, wherein R - R2 = R3 = h, and n = 1. 2 CLAIMS 1. General formula compounds: CH CH 0 in which: R, R1 and R2, equal or different from each other, = H, halogen, Ci-C4 alkyl, CrC4 alkoxy; R3 = H, CH3; ch3 I A = -CHr; -CH-; n = 0 or 1; R4 = H, Cj-C5 alkyl optionally substituted with halogen atom, C3-C6 cycloalkyl, C2-C5 alkenyl, ethynyl, halogen, when n = 1, CN, SCN, phenyl optionally substituted with Cj-Cs alkyls or halogen atoms , 5- or 6-term heterocyclic groups containing from 1 to 3 heteroatoms, acetyl, COO-alkyl, -OR3; -SR5, -N-R5 [with R5 and R6, equal or of- THE R6 verses among them; = H, CrC5 alkyl, C2-C5 alkenyl, C2-C5 alchemy, phenyl, 5 or 6-term heterocyclic group containing 1 to 3 heteroatoms, S02-alkyl, acetyl] as long as - (A) n-R4 = CH3, at least between R, R1, R2 and R3 is different from hydrogen. The compound according to claim 2, characterized in that it is N-phenyl-N-chloroacetyl-3-amino-os-sazolidin-2-one. The compound according to claim 2, characterized in that it is N-phenyl-N-phenylacetyl-3-amino-os-sazolidin-2-one. 5. The compound according to claim 2, characterized in that it is N-phenyl-N- (ß-methyl-propionyl) -3-amino-oxazolidin-2-one. The compound according to claim 2, characterized in that it is N-phenyl-N-methoxyacetyl-3-amino-oxazolidin-2-one. 7. Compounds according to claim 1 wherein R = R1 = CHS, R2 = R3 = H. The compound according to claim 7, characterized in that it is N- (2,6-dimethylphenyl) -N-chloroacetyl-3 - amino-oxazolidin-2-one. The compound according to claim 7, characterized in that it is N- (2,6-dimethylphenyl) -N-phenacetyl-3 - amino-oxazolidin-2-one. The compound according to claim 7, characterized in that it is N- (2,6-dimethylphenyl) -N-methoxyacetyl - 3-amino-oxazolidin-2-one. The compound according to claim 7, characterized in that it is N- (2,6-dimethylphenyl) -N-acetoxyacetyl - 3-amino-oxazolidin-2-one. The compound according to claim 7, characterized in that it is N- (2,6-dimethylphenyl) -N-hydroxyacetyl - 3-amino-oxazolidin-2-one. The compound according to claim 7, characterized in that it is N- (2,6-dimethylphenyl) -N-carbometos-sicarbonyl [or N-methoxyoxalyl] -3-amino-oxazolidin - 2-one. The compound according to claim 7, characterized in that it is N- (2,6-dimethylphenyl) -N-acetyl-3-amino-oxazolidin-2-one. The compound according to claim 7, characterized in that it is N- (2,6-dimethylphenyl) -N-phenoxyacetyl - 3-amino-oxazolidin-2-one. 16. Fungicidal compositions having as active principle one or more of the compounds of general formula (I) according to claim 1. 17. Method for combating fungal infections in useful plants consisting in distributing on the plants, as such or in the form of suitable compositions, compounds of general formula (I) according to claim 1. 17. Method for combating fungal infections in useful plants consisting in distributing on the plants, as such or in the form of suitable compositions, compounds of general formula (I) according to claim 1. 18. Method for fighting fungus infections in useful plants according to claim 17, characterized in that the infection is due to Downy mildew of the vine - Plasmopa-ra viticola. 19. Method for combating fungal infections in useful plants according to claim 17, characterized in that the infection is due to Tobacco downy mildew - Downy mildew Tabacina.