CY1235A

CY1235A - N-aryl-n-acyl-3-amino-oxazolidin-2-one fungicides

Info

Publication number: CY1235A
Application number: CY1235A
Authority: CY
Original assignee: Montedison Spa
Priority date: 1979-09-07
Filing date: 1980-09-08
Publication date: 1984-06-29
Also published as: GB2058071A; JPS5655381A; JPH0240664B2; IL60950A; IL60950A0; ZA805450B; OA06743A; ES8106713A1; CA1203539A; ES494856A0; DE3033161A1; BE885117A; BR8005645A; FR2464649B1; AU6194980A; KE3383A; AR228138A1; GB2058071B; IT1123564B; AU545683B2

Description

GB 2 058 071 A

SPECIFICATION

N-aryl-N-acyl-3-amino-oxazolidin-2-ones fungicides

5 The present invention relates to fungicides and in particular to 3-amino-oxazo!idin-2-ones which are 5

endowed with high fungicidal activity combined with low phytotoxicity.

Fungicidal compounds belonging to the class of N-phenyl-1,3-oxazolidin-2,4-diones, have been disclosed in Dutch Patent Application No. 68 17249, French Patent Specification No. 2172 295 and Italian Patent Application No. 20579 A 78.

10 Derivatives of aniline and glycine which carry on the nitrogen atom a substituted phenyl and anacylic 10

group have also been disclosed as possessing bactericidal and fungicidal activity.

In particular, the acylic group may consist of an a- or |5-haloalkanoyl as disclosed in German Offeniegungsschrift No. 2 513 789, an acetyl group substituted inthect-position with a sulphur or oxygen atom in its turn bound to groups of varying nature as disclosed in French Patent Application No. 7 510 722, or 15 a 2-furoyl, 2-thienoyl or pyridil-2-carbonyl group as disclosed in German Offeniegungsschrift Nos. 2 513 732 15 and 2 513 788. Similarly methylalaninates carrying on the nitrogen atom a 2,6-dialkyl-phenyl and a cyclopropanyl, acryloyi orcrotonoyl group have been disclosed in Swiss Patent Application Nos. 4.988 74 and 2.906 75 as possessing microbicidal activity.

Other derivatives of acyl-anilines have been disclosed in Belgian Patent Specification No. 863.615 and in 20 German Offeniegungsschrift No. 2 745 533 as possessing fungicidal activity. 20

The interest in the search for new derivatives from acylanilines having a fungicidal action, originates from the need for finding acylaniline derivatives which possess high fungicidal activity combined with low phytotoxicity. Some of the known products, although possessing excellent fungicidal activity also prove to be toxic for the plants that are to be protected against fungal infections. The damage caused by the 25 phytotoxicity to the plants to be protected can barely be avoided by using a dose of fungicidal compound 25 that may be the best compromise between the fungicidal activity of the compound and its phytotoxicity.

In fact, in the practical application in agricultural cultivations, the quantity of product that actually remains on the plant, varies considerably depending on various factors, for example, the weather conditions (particularly the frequency of rainfall), the correctness and frequency of the application of the fungicide 30 carried out by the farmer. 30

Therefore there is a current need for fungicidal compounds having a good fungicidal activity and at the same time a low phytotoxicity thereby offering a large safety margin so that even large quantities of the product do not cause damage to the plants treated.

The invention has been made with the above points in mind.

35 According to the invention there is provided a method for combatting fungal infections on useful plants 35 which comprises contacting the plants on their growing medium with a compound of the general formula:

40 40

(I)

45 I 4 45

50 „2 50

in which

R, R1 and R2 independently represent a hydrogen or halogen atom, an alkyl group containing 1 to 4 carbon 55 atoms or an alkoxyl group containing 1 to 4 carbon atoms, 55

R3 represents a hydrogen atom or CH3,

CH3

A represents -CH2- or -CH-,

60 nis0or1,and 60

R4 represents a hydrogen atom, an alkyl group having 1 to 5 carbon atoms which may be substituted with one or more halogen atoms, a cycloalkyl group having 3 to 6 carbon atoms, an alkenyl group having 2 to 5 carbon atoms, an ethynyl group, a halogen atom when n is 1, CN, SCN, a phenyl group which may be substituted with one or more substituents selected from alkyl groups of 1 to 5 carbon atoms and halogen 65 atoms, a heterocyclic group having 5 to 6 atoms in the ring and containing from 1 to 3 hetero-atoms, an 65

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2

acetyl group, COO-alkyl, -OR5, SR5 or -N-R5

in which R5 and R6 independently represent a hydrogen atom, an alkyl group of 1 to 5 carbon atoms, an alkenyl group of 2 to 5 carbon atoms, an aikynyi group of 2 to 5 carbon atoms, a phenyl group, a heterocyclic group having 5 or 6 atoms in the ring and containing from 1 to 3 hertero-atoms, S02-alkyl or an acetyl group.

10 The above compounds of formula (I) are endowed with high fungicidal activity and exhibit very low <|q phytotoxicity.

Only one of the compounds falling under general formula (I) is known in the literature, namely N-phenyl-N-acetyl-3-amino-oxazolidin-2:one of the following formula (II):

15 r \ 15

(II)

20 K J H 20

This compound has been disclosed in the "Journal of Organic Chemistry", 31, p. 968 (1966) and has not been recognized as possessing a fungicidal activity.

25 Therefore according to a further embodiment of the invention there is provided compounds of general 25 formula (I) as described above with the proviso that when -(A)n-R4 is CH3 at least one of the radicals R, R1, R2 and R3 is other than hydrogen.

The preparation of the compounds of general formula (I) is conducted utilizing processes analogous to those known in the normal practice of organic chemistry.

30 For example, an arylhydrazine (3) may be prepared by reacting the corresponding aniline (1) with sodium 30 nitrite (NaN02) in hydrochloric acid, and by then reducing the diazonium salt (2) thus obtained as described for instance in "Journal of American Chemical Society", 81, p.4673 (1959) and shown in the following reaction scheme 1, equation 1.

The aryl-hydrazine (3) is then reacted with 2-halo-ethy! or 1 -methyl-2-haloethyl-chloroformiate (4) (e.g.

35 prepared by the action of phosgene on a halo-hydrine) in the presence of a base, and the intermediate (5) 35 thus obtained is then cyclized in the presence of bases, thereby obtaining intermediate (6) as shown in the following reaction scheme 1, equation 2. This type of reaction has been disclosed in Journal of American Chemical Society 45,1951 (1926).

Intermediate (6) is then condensed with a suitable acylic halide (7), according to known techniques as

40 shown inthe following reaction scheme 1, equation 3. The condensation reaction between intermediate (6) 40 and acylic halide (7) may be substituted or replaced by analogous reactions known in the literature which allow the introduction of suitable acylic groups. For example, the compounds of general formula (I), in which the acylic part:

45 R5 45

R4 is —OR5; -SR5; -N

R6

50 50

may be prepared by reacting intermediate (6) with phosgene or with halo-acetyl orhalopropionyl halides,

e.g.,

CI-C-CH2CI and CI-C-CH-CH3,

55 55

O O CI

followed by substituting the halogen atom according to known techniques.

The compounds of formula (I) in which the acylic part is

60 60

-C-R4,

!|

O

65 and in which R4 = NHR5, may be prepared by reacting intermediate (6) with an isocyanate of the formula: 65

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GB 2 058 071 A 3

R5 - N = C = 0.

The compounds of formula (I), in which the acylic part is 5 - C - CH2 - C - CH3 (A = CHZ, R4 = acetyl),

0 O

may be prepared by reacting the intermediate (6) with diketene.

10

Reaction Scheme 1:

15

20

1) R

NaNO„/HCl

-> R

K=S®C1°

Reducer

NK-NH.

> R

10

15

20

25

30

35

40

45

R

I

2) (3) + Cl-C-0-CH-CH2X

O

(4)

(5) -HX

NH-NH-C-O-CH-CH-X

II 2

R"L O

(6)

25

30

35

40

45

50

3}

(6) + X-C-(A)n-R4 —^ (I)

(7)

50

In the above reaction scheme X represents halogen and R, R1, R2, R3, R", A and n are as defined with respect to general formula (I)

Reaction 3) is carried out in an inert solvent, in the presence of halogenhydric acid accepting base, at reflux 55 temperature.

The compounds of general formula (I) are endowed with an excellent fungicidal activity against phytopathogenous fungi and their action has both a preventive character i.e. they hinder the arising of the disease, as well as a curative character, i.e. they are active against an existing infection.

One of the most important classes of phytopathogenous fungi which can be fought by using the 60

compounds of the invention, is that of Phycomicetes which comprises Plasmopara spp., Phytophtora spp., Peronospora spp., Pseudopersonospora spp. and Phthium spp.

The fungicidal compounds of the invention are useful for combatting fungal infections on useful plants such as vine, tomato, tobacco, potato and other cultivations. The compounds possess good systemic 65 characteristics, i.e. they are carried into the various parts of the plants, and it is possible to apply these 65

55

60

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products both on the leaves as well as on the soil. Moreover, the compounds of general formula (I) prove to be compatible with the plants that are to be protected against fungal attacks.

The majority of the compounds of general formula (I) have not shown any sign of phytotoxicity during testing, while the remainder exhibited only a low phytotoxicity, lower than that of comparable known 5 fungicides. ^

In the practical agricultural applications the fungicide compounds of formula (I) can be used as such or in the form of suitable compositions containing the compounds of formula (i) as active principle together with solid or liquid inert carriers and optionally surfactants and other additives. Other active compounds such as other fungicides, inserticides and plant-growth regulators may be included in the compositions. The "

10 compounds may be formulated, according to conventional practice, as dusts, powders, wettable powders, emulsifiable liquids and granular formulations.

The amounts of compounds of formula {l)to be distributed for fighting fungal infections depends on various factors, e.g. the active compound used, the type of composition or formulation, the type of infection and its severity, the type of agricultural cultivation to be protected from fungal attack and the climatic and 15 weather conditions. Generally, amounts of fungicidal compounds of formula (I) in the range of 10 and 500 g/ha are sufficient, the preferred amount being of from 100 to 250 g/ha.

The invention will now be illustrated by the following Examples.

EXAMPLE 1

20 Preparation of N-{methoxyacetyl)-N-(2,6-dimethyl-phenyl)-3-amino-oxazolidin-2-one 20

A) Preparation of 2,6-dimethy/pheny/hydrazine

107 g of 2,6-xylidine were dripped into a solution of 220 ml of concentrated HCI in 150 ml of water. After cooling to -5°C, the mixture was additioned with a solution of 66 ml of NaN02 in 150 ml of H2O, over a period of time of about 1 hour and under vigorous stirring. The yellow-orange coloured suspension thus obtained 25 was additioned with 450 g of SnCI2.2H20 in 600 ml of a 5N aqueous solution of HCI at 0=C over a period of 4 25 hours. The mixture was then maintained understirringfor 24 hours, allowing the temperature to rise up to +20°C. The solid which formed was filtered, dissolved in 700 ml of H20 and then treated with a solution of 230 g of NaOH in 300 ml of H20, at a temperature of between 10 and 15°C, and thereafter the produced was extracted with diethyl-ether (3 x 250 ml).

30 The etherial extract, after washing with H20 and drying over Na2S04 was made up to a volume of 1500 ml 30 with diethylether and then was treated with anhydrous gases HCI, until complete precipitation of the chlorohydrate of the 2,6-dimethylhydrazine was attained. The salt was then filtered and dried, yield 40 g of a white solid having a melting point of 205 to 207=C with decomposition. 2,6-dimethylphenylhydrazine was obtained from the chlorohydrate by treatment with NaOH.

35 , 35

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

36.5 g of 2,6-dimethyI-phenylhydrazine(from A), and 18 g of pyridine in 100 ml of benzene were added at 10°C to 41.4 g of 2-bromoethyl-chloroformiate, prepared from phosgene and ethylenic bromohydrine, in 200 ml of benzene. On completion of the addition, the temperature was allowed to rise to 20*C under constant 40 vigorous stirring. The pyridine chlorohydrate was removed by washing with water. The benzenic solution 40 was then further washed with HCI and with water to a neutral pH, and was then dried over Na2S04 and evaporated to yield 61 g of an oily product which, crystallized from ligroin, yield 43 g of a light coloured solid having a melting point of 58 to 63=C, and which consisted of 1-{2,6-dimethyl-phenyl)-2-(jVbromoethyl)-oxycarbonyl hydrazine (intermediate A). IR spectroscopy indicated v(C=0) = 1710 cm-1; v (NH-CO) = 3180 45 cm-1; \(NH-Ar) = 3340 cm-1.40 g of this intermediate were dissolved in 500 ml of toluene and treated with 45 16 g of tetramethylguanidine. The mixture was reflux-heated for 3 hours under stirring. After cooling, the mixture was washed with 200 ml of H20 and then with 100 ml of HCI and finally again with 200 ml of H20. The aqueous phases, reunited, were extracted with CH2CI2 (2 x 200 ml).

The combined organic phases were dried over Na2S04 and then the solvent was evaporated, to yield a *

50 solid residue which was crystallized from ligroin-ethylacetate (2:1). 50

22.5 g of 3-(2,6-dimethyianiline)-oxazolidin-2-one (intermediate (B)) having a melting point of 107 to 110°C were obtained. IR spectroscopy indicated: v (C=0) = 1770 cm-1 v(NH) = 3340 cm-1. »

The cyclization reaction was repeated, dissolving the intermediate (A) having a melting point of 58to62°C, in ethanol containing sodium ethylate, and by then reflux-heating the solution. After an analogous treatment 55 of the reaction mixture, the intermediate (B) was isolated melting at 107 to 110CC. 55

C) 1.1 g of methoxyacetyl chloride were added to 2 g of intermediate (B), in 70 ml of toluene and 0.2 ml of dimethyiformamide. The reaction mixture was reflux-heated for 8 hours. After cooling the reaction mixture was subjected to complete evaporation of the solvents. The residue, consisting of 2.9 g of a thick oily product, was purified on a silica gel column, using as eluent a mixture of benzene/ethylacetate (in a 1/1 ratio).

60 After removal of the solvents, 1.1 g of a syrupy product was obtained which crystallized spontaneously. After 60 re-crystallization from ligroin/ethylacetate (1:1) mixture, 1 g of the desired compound was obtained whose characteristics have been reported in Table 1 (Compound No. 6).

The IR spectroscopy indicated: (N-CO-CH2) = 1680 cm-1; v (N-CO-O) = 1780 cm-1.

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GB 2 058 071 A

EXAMPLE 2 ■ .

Adopting aniogous procedures to those described in Example 1, the compounds reported in the following

Table 1 were prepared.

2 £ oc o o O)

r-

V

o o

CO

00

CO

r-

CO

Is".

00

r>

pN

r*.

r-»

r**

h-

1^.

T—

*—

T—

*■—

T—

*—

*1"

o o

o

IT)

©

o o

o

©

o o

o

<7>

00

CO

r*

CO

O)

cn

00

O)

CD

CO

*—

t—

*■"

*—

*-

*—

*■"

t—

*—

u>

• i r- CM fs. P-

CN <Ji i

00 CO

CO

o

*—

CN

a>

00

to t—

CO

IX>

CO

CN

C3

o

00

:= CO

T—

CO

o

o t-

T™■

*—

t—

o

5o

U)T u> -T-' -r-'1—

X ^ Xnr>U

#n y J. i ^

(JUjOQOOOOU

I o o o o

o

XXXIXXXXX , X X p < ooooouooo oo

LU

X

H H H H

I

X

H H H H

X

CO

o n n rt

CO

X

X XX

X

a a

9i99

o a

o

CO

to CD CO

CO

n X

r, X

co co X X

m X

CO

X

CO

X

x x x 9

a

9 x a o o

O

i a

CN

CM

OJ CN

CN

CM

CN

-a c

3

o is o a

[MW^tfltDI^OOOO

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GB 2 058 071 A

Notes to Table I:

(1) Theelementalanalysisofallthecompoundsisconsistentwiththeassignedstructure.

(2) Melting points have not been corrected.

(3) Only the bands corresponding to vC=0 are reported.

5 (4) vOH = 3300 cm-1. .5

EXAMPLE 3

Curative activity on vine Peronospora. (Plasmopara viticola (B. et C.) Ber! et de Toni).

Vine leaves of Cv. Dolcetto, grown in pots in a conditioned environment stabilized at 25CC and 60% relative 10 humidity, were besprinkled on the lower leaf surface with an aqueous suspension of Plasmopara viticola 10 conidia (200,000 conidia cc). After 24 hours in a humidity (moisture) saturated environment, stabilized at 21 °C, the plants were treated by besprinkling both leaf surfaces with the products under examination in a water-acetone solution of 20% acetone (vol. vol.). At the end of the incubation period (7 days), the degree of infection was assessed visually on the basis of the following evaluation scale:

15 0 no control, infection equal to that of control plants (infected by non-treated plants), 15

1 1 to 20% reduction of the infection,

2 20 to 60% reduction of the infection,

3 60 to 90% reduction of the infection,

4 reduction of the infection greaterthan 90%.

20 Table II reports the results of these tests. 20

TABLE II

Curative activity against vine Peronospora by folia application at the dose of 0.5°o. 25 25

Compound No. Activity Compound No. Activity

1 3 7 4

2 3 8 4

30 3 4 9 4 30

4 4 10 4

5 4 11 4

6 4 12 4

35 EXAMPLE 4 35

Curative activity on Peronospora of Tobacco {Peronospora tabacina Adam)

The leaves of tobacco plants Cv. Burley, grown in pots in a conditioned environment, were besprinkled on the lower leaf surfaces with a Peronospora te£3£7/7aconidia-suspension (200,000 conidia cc). After 6 hours in a humidity saturated environment, the plants were transferred to a conditioned environment stabilized at 40 20*C and 70% relative humidity, for the incubation of the fungus. 24 hours after the infection, treatment was 40 carried out by besprinkling both leaf surfaces with the product under examination, in a water-acetone solution of 20% acetone (vol. vol.). At the end of the incubation period (6 days) the extent of the infection was visually assessed in accordance with Example 3. The results of the tests are reported in Table III.

45 TABLE III 45

Curative activity by foliar application at does of 0.5% on plants infected with Peronospora of Tobacco.

Compound No. Activity

50 50

4 4

6 4

EXAMPLE 5

55 Determination of degree of phytotoxicity 55

Leaves of Cv. Dolcetto vine plants, grown in pots in a conditioned environment stabilized at 25JC and 60% relative humidity, were treated by besprinkling both leaf surfaces with a water-acetone solution of 20%

acetone (vol. vol.) of the products under examination. After 7 days the extent or degree of phytotoxic symptoms were evaluated visually according to an evaluation scale ranging from 100 (for fully damaged 60 plant) to 0 (for a healthy plant). The corresponding data is reported in Table IV in comparison with the 60

phytotoxicity indexes of the two known compounds 'Furalaxyl" disclosed in British Patent Specification No. 1 448 810 and 'Ridomil" disclosed in French Patent Specification No. 2 267 042.

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GB 2 058 071 A

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TABLE IV Phytotoxicity index for does at 0.6%. Compound No. Phytotoxicity index

1

0

3

10

4

0

6

0

'Furalaxyl'11'

100

'Ridomil''21

60

10 b , , 10

(1} 'Furalaxyf is N-{2,6-dimethylphenyl)-N-(1'-carbomethoxyethyl)-2-furoyl-amide:

15 15

CH3 q y

H-CO - C - CH c—/r >

3 y T_J

CH3

20 I 20

£

25 (2) 'Ridomil' is N-(2,6-dimethylphenyl)-N-(1'-carbomethoxy-ethyl)-methoxyacetamide: 25

30 0 x / 30

35 35

Claims

1. A method for combatting fungal infections on useful plants, which comprises contacting the plants, or their growing medium with a compound of general formula: 40 , 40

\/°

CH

(X)

45 , 45

50 R LT\ c 50

55 55

in which

R, R1 and Rz independently represent a hydrogen or halogen atom, an alkyl group containing 1 to 4 carbon atoms or an alkoxyl group containing 1 to 4 carbon atoms,

R3 represents a hydrogen atom orCH3 60 ch3 60

I

A represents -CH2- or -CH-;

n isO or 1, and

R4 represents a hydrogen atom, an alkyl group having 1 to 5 carbon atoms which may be substituted with 65 one or more halogen atoms, a cycloalkyl group having 3 to 6 carbon atoms, an alkenyl group having 2 to 5 65

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8

carbon atoms, an ethynyl group, a halogen atom when n is 1,CN,SCN, a phenyl group which maybe substituted with one or more substituents selected from alkyl groups of 1 to 5 carbon atoms and halogen atoms, a heterocyclic group having 5 or 6 atoms in the ring and containing from 1 to 3 hetero-atoms, an acetyl group, COO-alkyl, -OR5, SR5 or -N-R5

5 ! 5

R6

in which Rs and R6 independently represent a hydrogen atom, an alkyl group of 1 to 5 carbon atoms, an alkenyl group of 2 to 5 carbon atoms, an alkynyl group of 2 to 5 carbon atoms, a phenyl group, a heterocyclic

10 group having 5 or 6 atoms in the ring and containing from 1 to 3 heteroatoms, S02-alkyl or an acetyl group. 10

2. A method as claimed in Claim 1 in which the fungal infection is caused by Peronospora of vine (Plasmopara viticola).

3. A method as claimed in Claim 1 in which the fungal infection is caused by Peronospora of Tobacco (Peronospora tabacina).

15

4. A method of combatting fungal infections on useful plants as claimed in Claim 1 substantially as 15

herein described with reference to anyone of the Examples.

5. Compounds of the general formula:

R3 \

20 * 20

(i)

25 •„ T 25

30 / 30

in which R, R\ R2, R3, R4, A and n are as defined in Claim 1 with the proviso that when (A)n-R4 is CH3 at least one of R, R1, R2and R3 is otherthan hydrogen.

35

6. A compound as claimed in Claim 5 in which R = R1 = Rz = R3 = hydrogen and n is 1. 35

7. N-phenyl-N-chloro-acetyl-3-amino-oxazolidin-2-one.

8. N-phenyl-N-phenylacetyl-3-amino-oxazolidin-2-one.

9. N-phenyI-N-(|3-methyl-propionyl)-3-amino-oxazoiidin-2-one.

10. N-phenyl-N-methoxyacetyl-3-amino-oxazolidin-2-one.

40 11. A compound as claimed in Claim 5 in which R = R1 = CH3, R2 = R3 = hydrogen. 40

12. N-{2,6-dimethylphenyl)-N-chloroacetyl-3-amino-oxazolidin-2-one.

13. N-{2,6-dimethylphenyl)-N-phenylacetyl-3-amino-oxazolidin-2-one.

14. N-(2,6-dimethylphenyl)-N-methoxyacety[-3-amino-oxazolidin-2-one.

15. N-(2,6-dimethylphenyl)-N-acetoxyacetyl-3-amino-oxazolidin-2-one.

45 16. N-(2,6-dimethylphenyl)-l\l-hydroxyacetyl-3-amino-oxazolidin-2-one. 45

17. N-(2,6-dimethylphenyl)-N-carbomethoxycarbonyl [or N-methoxyoxalyl]-3-amino-oxazolidin-2-one.

18. N-(2,6-dimethylphenyl)-N-acetyl-3-amino-oxazolidin-2-one.

19. N-(2,6-dimethylphenyl)-N-phenoxyacetyl-3-amino-oxazolidin-2-one.

20. A compound as claimed in Claim 5 substantially as herein described with reference to any one of the ? 50 Examples. 50

21. Afungicidal composition containing as an active ingredient a compound as claimed in any one of claims 5 to 20.

Printed for Her Majesty's Stationery Office, by Croydon Priming Company Limited, Croydon, Surrey, 1981. Published by The Patent Office, 25 Southampton Buildings. London, WC2A1AY, from which copies may be obtained.

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