CH653676A5 - FUNGICIDE COMPOUND. - Google Patents

Description

The present invention relates to a fungicidal compound and more precisely to the compound N- (2,6-dimethylphenyl) -N - methoxyacetyl-3-amino-1, 3-oxazolin-2-one, its use as a fungicide and a process for its preparation. 55 In Italian patent applications No. 25,538 A / 79 (Monte-dison SpA) and No. 24,168 A / 80 (Sandoz AG), fungicidal compounds belonging to the class of N-aryl-N-aciI-3-amino-oxazolidin have been described -2-ones.

In the above compounds, the aryl group consists of a diethyl optionally substituted with groups of various nature such as alkyls, alkoxyls and halogens; the acyl group derives from different carbosilic acids such as variously substituted saturated or unsaturated aliphatic acids, aromatic, heteroaromatic acids, etc.

Alkyl groups may also be present in position 65 4 or 5 of the oxazolidine ring.

We have now found and forms the object of the present invention, the compound N- (2,6-dimethylphenyl) -N-methoxyacetyl-3-ammi-no-1, 3-oxazolin-2-one of formula:

3

653 676

CH20CH3

Compound I is endowed with high fungicidal activity and as such it is particularly useful in the defense of crops useful from the fungal attack.

The preparation of the compound I can be conveniently carried out by means of a three-step process as described below.

In the description of the process object of the invention the following symbols are introduced for simplicity:

R = CH2OCH3

Ar = H ^ C

The first stage of the process consists in the condensation of a 2,2-dialkoxy-ethyl chloroformate (dialkylacetal glycolic aide dehydrogen chloride) (II) with an arylhydrazine (III) to obtain a 2,3- 3-arylcarbazate dialcossiatile (IV).

Also in this case, the reaction is carried out in an inert solvent and in the presence of an accepting base of halogenic acids.

The reaction does not require particular temperature conditions, for convenience it is preferred to operate at room temperature.

(I) The acyl halides of formula V are known compounds.

The third stage of the process consists in the cyclization of the 3-aryl-3-acyl-carbazate of 2,2-dialkoxy-ethyl (VI) obtained from the second stage.

The cyclization is carried out using sulfuric acid and can take place in a single stage when using concentrated (96%) H2SO4 in two stages using 50% H2SO4, isolating the intermediate N- (2,6-dimethylphenyl) -N-methoxyacetyl -3-15-amino-4-hydroxy-1, 3-oxazolidin-2-one (VII) and treating the latter with concentrated H2SO4.

H2S04 at 50%

H „SO., Conc. 2 4

H> (i)

H SO "conc. 2 4

OH

THE

CH-CH "

j ^ v / n-ori ..

\ / N,

N N 0

(VII)

+ Ar-NH-NHg>

(I ^ I)

■ O Ar-NH-NH-C - 0 - CH2 - CH (OR1 ^

(IV)

[R1 represents a C1-C4 alkyl].

Reaction 1) is carried out in an inert solvent and in the presence of an acceptor base of hydrogen halide. It is generally preferred to operate at temperatures close to 0 ° C.

The chloroformates of formula II are known or easily prepared compounds by reaction of phosgene (COCI2) with an acetal of the glycolic aldehyde.

The second stage of the process consists in the acylation with the appropriate acyl halide (V) of the carbazate (IV) obtained from the first stage.

r> Ar-N-NH-C-O-CH -CH (OR1) (VI)

LI l

The reaction 3, both when carried out using concentrated sulfuric acid 40 and with more diluted acid, is carried out by directly adding the carbazate (VI) to the sulfuric acid and leaving the mixture under stirring for a few minutes at room temperature until complete dissolution.

The third stage of the process can likewise be conducted by replacing sulfuric acid with other concentrated strong acids.

Compound I is also useful as an intermediate for the preparation of compound N- (2-dimethylphenyl) -N-methoxyacetyl-3-amino-1, 3-oxazolidin-2-one (described in the previously cited Italian patent applications) by hydrogenation of the 50 double bond in the oxazolinonic ring.

The hydrogenation reaction is carried out with hydrogen in the presence of a suitable catalyst.

As previously mentioned, compound I has a fungicidal activity towards phytopathogenic fungi.

55 Its action is both preventive (ie preventing the onset of the disease) and curative (when the infection is already in progress).

It also has good systematic characteristics (that is, it is transported to the various parts of the plant).

60 For practical uses in agriculture, the fungicide of formula I can be used as such or in the form of a suitable composition.

Said composition is constituted by compound I as active principle, by a solid or liquid carrier and possibly 65 by surfactants and other additives.

The fungicidal compound object of the invention can be formulated, according to known techniques, in emulsifiable liquids, dry powders, wettable powders etc.

1)

Çl-Ç-0-CH „-CH (0R)

i does C

0

(II)

2)

(IV) + R-C-Z

II

0

(V)

653 676

4

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

The quantity of compound of formula I necessary to obtain a good protection of agricultural crops from fungal attack depends on various factors such as the type of composition or formulation, the type of fungus to be combated and the degree of infection, the type of cultivation to be protected, climatic and environmental factors.

In order to better illustrate the invention, the following examples are provided.

Example 1

Preparation of the 2,2-diethoxy-ethyl chloroformate of formula:

CI — C-O-CH —CH (OC H)

d d O d

0 = C

/

CH -O-CH 2 3

\.

CH ^ N-NH-C-O-CH -CH (OC H) W y II ^ 2 5 2

<2>

II

0

To a solution of 2.45 g of phosgene (COCl2) in 40 ml of toluehe kept at 5 ° C, 20 ml of a toluenic solution containing 3.5 g of diethylacetal of the glycolic aldehyde are added by dripping [HO-CH2-CH (OC2Hs) 2] and 3 g of triethylamine.

The reaction mixture is left for 12 hours, then is filtered to separate the precipitate (triethylamine hydrochloride).

The volatile components of the mixture are then removed by evaporation under reduced pressure thus obtaining a colorless liquid residue (4.5 g).

The residue is then distilled under vacuum collecting the fraction which boils at 80-82 ° C at the pressure of 22.6 mbar (2.8 g) made up of the desired product which is presented as a colorless liquid. 35

IR 1780 cm "1 (u C = 0).

Example 2

Preparation of 3- (2,6-dimethylphenyl) -carbazate of 40

2,2-diethoxyethyl of formula:

To a solution of 3- (2,6-dimethylphenyl) -carbazate of 15 2,2-diethoxyl prepared as described in Example 2, and 1,11 g of triethylamine in 60 ml of toluene is added by dripping at room temperature a 1.2 g solution of methoxyacetyl chloride in 10 ml of toluene.

The reaction mixture is kept under stirring at room temperature for 4 hours, then the solvent is removed by evaporation under reduced pressure.

The semisolid residue is taken up with 50 ml of diethyl ether and the insoluble is removed by filtration.

From the filtrate the solvent is removed by evaporation at 25 reduced pressure to obtain 3.8 g of the desired product which is purified by chromatography on a silica gel column (eluent ethyl acetate-toluene in a 1: 1 ratio).

IR 3260 cm1 (u NH), 1750 cm1 (u C = 0), 1700 cm1 (u C = 0).

30

Example 4

Preparation of the N- (2,6-dimethylphenyl) -N- (methoxyacetyl) - 3-amino-1, 3-oxazolin-2-one of formula:

0 = C

/

ch2-or-CH3

CH = CH.

(THE)

O) - nh-nh-c-o-ch2-ch <oc2h5) 2 o

To a solution of 1.8 g of 2,6-dimethylphenylhydrazine and 1,62 g of triethylamine in 100 ml of methylene chloride, kept under stirring at 5 ° C, 2,8 g of chloroformate prepared according to what described in Example 1. The reaction mixture is left for 12 hours, then the solvent is eliminated by evaporation under reduced pressure.

The residue is taken up in 50 ml of diethyl ether and the insoluble (triethylamine hydrochloride) is separated by filtration.

The solvent is again eliminated by evaporation under reduced pressure to obtain 3.1 g of pale yellow oil consisting of the desired product.

IR 3340 cm1 (u NH-CO), 1720 cm "1 (u C = 0).

Example 3

Preparation of the 3- (2,6-dimethylphenyl) -3-methoxyacetyl carbazate of 2,2-diethoxyethyl of formula:

2.4 g of the carbazate obtained as described in Example 3 are dissolved in 20 ml of concentrated H2SO4 (96%) kept under stirring at room temperature.

After 15 minutes the reaction mixture is poured onto 40 g of ice and then neutralized with 30% NaOH.

The resulting mixture is extracted with ethyl acetate (2 x 50 ml) and with methylene chloride (2 x 50 ml).

The combined organic phases are dried over anhydrous Na2SO4, then the solvents are eliminated by evaporation under reduced pressure. 1.2 g of a reddish oil consisting of the desired product are thus obtained, which is purified by thin layer chromatography (eluent ethyl acetate - toluene in a 35: 65 ratio) obtaining 1 g of product.

IR 3140 cm1 (u CH = CH), 1780 cm'1 (u C = 0), 1700 cm1 (u C = 0).

Example 5

65 Preparation of the same product of Example 4 in two stages with isolation of the intermediate N- (2,6-dimethylphenyl) -N - methoxyacetyl-3-amino-4-hydroxy-1, 3-oxazolidin-2-one of formula:

5

653 676

The synthesis of Example 4 was repeated in a similar way, however using 50% sulfuric acid instead of concentrate. The processing of the reaction mixture according to procedures identical to those described in Example 4 allowed to isolate the 3-amino-4-hydroxy-oxazolidinonic intermediate in the form of a white crystalline solid (m.p. = 130-132 ° C).

IR 3260 cm "1 (u OH), 1790 cm1 (u C = 0) 1690 cm1 (u C = 0).

By treating this intermediate with concentrated sulfuric acid, the compound described in Example 4 was obtained having the same characteristics.

Example 6

Determination of the fungicidal activity of the compound N - (2,6 - di-methylphenyl) -N-methoxyacetyl-3-amino-1, 3-oxazolidin-2-one.

- Curative fungicidal activity against Plasmopara viticola.

Some Dolcetto cv vine plants grown in pots in a conditioned environment were sprayed on the underside of the leaves with an aqueous suspension of conidia of P. viticola (B. et C.) Beri et de Toni (200,000 conidia / ml).

After 48 hours of staying in an environment saturated with humidity at 21 ° C, the plants were separated into two groups. A group of plants was treated by spraying on both leaf pages with a hydroacetonic suspension (20% by volume of acetone) of the product concerned.

All the plants were then transferred to an environment conditioned at 25 ° C and 60% relative humidity.

At the end of the mushroom incubation period (7 days) the degree of fungal infection of the treated plants was assessed in comparison with that of the infected and untreated plants.

At the 100 ppm dose the title compound showed 15 100% reduction of the infection.

- Curative fungicidal activity against Downy mildew tabacina.

Some cv tobacco plants. Potted cultivated burleys were sprayed on the underside of the leaves with an aqueous suspension of conidia of P. tabacina Adam (200,000 cones-2o of / ml). After 6 hours of stay in an environment saturated with humidity, the plants were divided into two groups and transferred to an environment conditioned at 20 ° C and 70% relative humidity for the incubation of the fungus.

48 hours after infection, a group of plants was treated by spraying on both leaf pages with a hydroacetonic suspension (20% by volume of acetone) of the product under examination.

At the end of the incubation period (6 days) the degree of fungal infection of the treated plants was assessed in comparison with 30 infected and untreated plants.

At the 100 ppm dose the title compound showed 100% reduction of the fungal infection.

v

Claims (6)

653 676 2 (VI) or 0 CH, is (wherein R1, has the above meaning) and finally the compound of formula (VI) is cyclized by treatment with a strong acid. 2. A process for preparing the compound of claim 1, characterized in that a 2,2-dialkoxy ethyl chloroformate of formula: Cl-C-0-CHo-CH (OR "1)» (II) The 2 2 0 (wherein R1 = C1-C4 alkyl) is condensed with an aryl-hydrazine of formula: NH - NH, (IH) in an inert solvent and in the presence of a halogen hydric acid acceptor base to obtain a 2,2-dialkos-siethyl 3-aryl carbazate of formula: NH-NH-C-O — CH0-CH (OR1) „(IV) The 2 2 OR (wherein R1 has the above meaning) and the compound (IV) is reacted with an acyl halide of formula: CH O-CH -C-Z or c " (V) (wherein Z represents a chlorine or bromine atom) in an inert solvent and in the presence of a hydrogen halide acceptor base to obtain a 2,2-dialkoxy-ethyl 3-aryl-3-acyl-carbazate of formula: / CH20CH3 0 = c ph ^ N-NH-C-O-CH -CH (OR1) 'The 2 CLAIMS 1. The compound N- (2,6-dimethylphenyl) -N-methoxyacetyl-3-am-mino-1, 3-oxazolin-2-one of formula CH2OCH3 (THE) 3. Process according to claim 2, characterized in that the cyclization of the intermediate VI is carried out in 20 concentrated sulfuric acid. 4. Process according to claim 2, characterized in that the cyclization of the intermediate (VI) is carried out in 50% sulfuric acid obtaining an intermediate of formula: (VII) and this is then treated with concentrated sulfuric acid. 40 5. A process for combating fungal infections in useful plants consisting in distributing an effective quantity of the compound of claim 1 on crops, as such or in the form of a suitable composition. 6. Fungicidal compositions containing the compound of claim 1 as an active principle, alongside inert carriers and possibly other additives.