1-phenoxy-1-triazolyl-butanol esters of carbamic acids,their preparation and their use as fungicides

1-Phenoxy-l-triazolyl-butanol esters of carbamic acids, their preparation and their use as fungicides

BAYER AKTIENGESELLSCHATT

c. 52307 a The present invention relates to certain new 1-phenoxy-1triazolyl-butanol esters of carbamic acids, to a process for their preparation and to their use as fungicides.

It has already been disclosed that 1-phenoxy-3-(1,2,4triazolyl)-3,3-dimethylbutan-2-ol esters, such as, in particular, 2-alkylcarbonyloxy-3,3-dimethyl-1-phenoxy-1- (1,2,4-triazol-1-yl)butanes substituted in the phenyl part, have good fungicidal properties (see DT-OS (German Published Specification) No. 2,600,799) and also Israel Patent Specification 51230). However, their action is not always completely satisfactory, especially when low amounts and low concentrations are used. Furthermore, it has been generally known for a relatively long time that zinc ethylene-1,2-bis-dithiocarbamidate is a good agent for combating fungal diseases of plants (see Phytopathology 33, 1113, (1963)). However, it is possible to use it only to a limited extent, since in some cases it is of low activity when low amounts and concentrations are used.

The present invention provides, as new compounds, 1-phenoxy1-triazolyl-butanol esters of carbamic acids of the general formula

<img file="IL56378A_D0001.tif" />

(I) in which

R represents halogenoalkyl, alkoxycarbonyl, alkoxyalkyl, phenyl substituted with one or more substituents selected from alkyl, alkoxy or alkoxycarbonylalkenyl, and alkylsulphonylalkenyl-carbamoyl,

X represents halogen or phenyl or nitro, and n represents 0, 1 or 2, the substituents X being selected independently of each other when n is 2 and their acid-addition salts and metal-salt complexes which have powerful fungicidal properties.

Preferably, R represents halogenoalkyl with up to carbon atoms, alkoxycarbonyl with 1-4 carbon atoms in the alkyl part, alkoxyalkyl with 1 to 4 carbon atoms in each alkyl part, or alkylsulphonyl-alkenyl-carbamoyl with 1 to 4 carbon atoms in the alkyl part and 2 to 4 carbon atoms in the alkenyl part, or represents monosubstituted or polysubstituted phenyl, each substituent being selected independently from straightchain or branched alkyl with 1 to 4 carbon atoms, alkoxy and alkoxycarbonyl-alkenyl with 1 to 4 carbon atoms in the alkyl part and 2 to 4 carbon atoms in the alkenyl part, and .

n is 0, 1 or 2.

The compounds of the formula (I) have two asymmetric carbon atoms; they can therefore exist in the erythro form and in the threo form. In both cases, they are predominantly in the form of racemates.

Surprisingly, the compounds according to the invention exhibit a considerably higher fungicidal activity than similar compounds known from the state of the art, such as, in particular, 2-alkylcarbonyloxy-3,3-dimethyl-l-phenoxy-156378/2 (1,2,4-triazol-1-yl)-butanes substituted in the phenyl part, which are very closely related compounds chemically and from the point of view of their action, and than zinc ethylene-1,2,-bisdithiocarbamidate, which is a known substance of the same type of action (see Tables A, B and C herein).

The invention also provides a process for the preparation of the compounds of formula (I), in which a triazolyl derivative of the general formula

OH

O- 0 - CH - CH - C(CH_s)₃

I (II)»

X ^nxN L_i in which

X and n have the meanings stated above, (a) is reacted with an isocyanate of the general formula = C = N - R (HI)» in which R has the meaning stated above, in the presence of a solvent and optionally in the presence of a catalyst, or (b) is reacted with a substituted l,3,4-dioxazol-2-one of the formula

R

<img file="IL56378A_D0002.tif" />

(IV), in which

R has the meaning stated above, in the presence of a solvent and optionally in the presence of a catalyst.

Furthermore, the compounds of formula (I) obtainable according to the invention can be converted into salts by reaction with acids, or the corresponding metal complexes can be obtained by reaction with metal salts.

If 1-( 4-biphenylyloxy) - 3,3־dimethy1-1- (1,2,4-triazoll-yl)-butan-2-01 and methoxymethyl isocyanate are used as starting materials in process variant (a), the course of the reaction can be represented by the equation which follows:

OH ^^-^^0־-CH-CH-C(CH3 )₃ + CH₃-O-CH,-N=C=O -.....—>>

<img file="IL56378A_D0003.tif" />

O-CO-NH-CHj-O-CH3 OO־°־f^H־^CH־^C(CH־

<img file="IL56378A_D0004.tif" />

If l-(4-biphe1ylyloxy)-3,3-dimethy1-1-(1,2,4triazol-l-yl)-butan-2-01 and 5־methoxymethyl-l,3,4-dioxazol2-one are used as starting materials in process variant (b), the course of the reaction can be represented by the equation which follows:

<img file="IL56378A_D0005.tif" />

״״

- C0₂

<img file="IL56378A_D0006.tif" />

0-C0-NH-CH2-O-CHj

Q־O־°־f^KH־^C(CH> >3

<img file="IL56378A_D0007.tif" />

־ 5 ־

The starting materials of the formula (II) are in general known (see German Offenlegungsschrift (German Published Specification) 2,324,010). Starting materials of the formula (II) which have not yet been described in the literature can be obtained by the processes already described, for example by reducing the corresponding ketone derivatives with aluminium isopropylate or with complex hydrides in the presence of a solvent.

The isocyanates of the formula (III) are known, or they can be prepared by processes which are generally customary and known, for example by reacting amines with phosgene and subsequently heating the product.

The l,3,4-dioxazol-2-ones of the formula (IV) are known (see G. Beck, Chem. Ber., 84, 688 (1951)) or they can be prepared by processes which are generally customary and known, for example by reacting corresponding hydroxycarboxylie acids or acid hydrazides with phosgene at the boil.

Preferred possible solvents for the reaction according to process variant (a) are all the inert organic solvents, especially ketones, such as diethyl ketone, and in particular acetone and methyl ethyl ketone; nitriles, such as propionitrile, and in particular acetonitrile; ethers, such as tetrahydrofuran or dioxan; esters, such as ethyl acetate; aromatic hydrocarbons, such as benzene or toluene; and halogenated hydrocarbons, such as methylene chloride, carbon tetrachloride or chloroform.

Preferred catalysts which can be used in process variant (a) are tertiary bases, such as triethylamine and pyridine, or organotin compounds, such as dibutyl-tin dilaurate.

The reaction temperatures can be varied within a substantial range when carrying out the process variant (a). In general, the process is carried out at from 0° to 100°C, preferably at from 20° to 70°C.

In carrying out process variant (a), equimolar amounts of the reactants are preferably used. In order to isolate the compounds of the formula (I), the solvent is distilled off and the residue is worked up by customary methods.

Le

A 18

Preferred possible solvents for the reaction according to process variant (b) are inert organic solvents, especially the solvents which have already been mentioned in the case of process variant (a).

Preferred catalysts which can be used in process variant (b) are tertiary amines, such as, for example, triethylamine, or alkali metal salts of fatty acids, such as, for example, sodium acetate.

The reaction temperatures can be varied within a substantial range in carrying out process variant (b). In general, the process is carried out at from 60° to 150°C, preferably at from 80° to 100°C.

In carrying out process variant (b), equimolar amounts of the reactants are preferably used. In order to isolate the compounds of the formula (I), the solvent is distilled off and the residue is worked up by customary methods.

As indicated above, the compounds (I) can be converted into acid-addition salts and metal salt complexes; it is preferred that these be physiologically acceptable.

It is possible to use all the physiologically acceptable acids for the preparation of acid addition salts of the compounds of the formula (I). Preferred acids include the hydrogen halide acids (for example hydrobromic acid and, especially, hydrochloric acid), phosphoric acid, nitric acid, sulphuric acid, monofunctional and bifuntional carboxylic acids and hydroxycarboxylie acids (for example acetic acid, maleic acid, succinic acid, fumaric acid, tartaric acid, citric acid, salicylic acid, sorbic acid and lactic acid) and sulphonic acids (for example ptoluenesulphonic acid and l,5־naphthalenedisulphonic acid).

The salts of the compounds of the formula (I) can be obtained in a simple manner by customary salt-formation methods, for example by dissolving a compound of the formula (I) in a suitable inert solvent and adding the acid, for example hydrochloric acid, and they can be isolated in a known manner, for example by filtration, and optionally purified by washing with an inert organic solvent.

A 18 620

־ 7 ־

Possible salts for the preparation of metal salt complexes of the compounds of the formula (I) are preferably salts of metals of main groups II to IV and of sub-groups I and II and IV to VIII, examples of metals which may be mentioned being copper, zinc, manganese, magnesium, tin, iron and nickel. Possible anions of the salts are those which are derived from physiologically acceptable acids, preferably the hydrogen halide acids (for example hydrochloric acid and hydrobromic acid), phosphoric acid, nitric acid and sulphuric acid.

The metal salt complexes of the compounds of the formula (I) can be obtained in a simple manner by customary processes, for example by dissolving the metal salt in alcohol, for example ethanol, and adding the solution to the compound of the formula (I). Metal salt complexes can be isolated in a known manner, for example by filtration, and optionally purified by recrystallisation.

Particularly active compounds according to the invention, in addition to those given in the preparative Examples hereinafter, are for example: l-(4-chlorophenoxy)-3j3־ dimethyl-2-methoxymethyl-carbamoyloxy-l-(l,2,4-triazol-lyl )־butane, 1-( 2,4-di chlorophenoxy)-3,3־־dimethyl2־-methoxyme thyl carbamoy loxy-1-( 1,2,4-triasol-l-yl)-butane, 1-(4chlorophenoxy)-3>3־dimethyl-2-trifluoromethylcarbamoyloxy-l(l,2,4-triazol-l-yl)-butane and l-(4-biphenylyloxy)־3,3־ dimethyl-2-trifluoromethylcarbamoyloxy-l-(l,2,4-triazol-lyl)-butane.

The active compounds according to the invention exhibit a powerful fungitoxic action. They do not damage crop plants in the concentrations required for combating fungi. For these reasons, they are suitable for use as plant protection agents for combating fungi. Fungitoxic agents are employed in plant protection for combating Plasmodiophoromycetes, Oomycetes, Chytridiomycetes, Zygomycetes, Ascomycetes, Basidjomycetes and Deuteromycetes.

The active compounds according to the invention have a broad spectrum of action and can be used against parasitic fungi which attack above-ground parts of

Le

A 18 620 plants or which attack the plants through the soil, as well as against seed-borne pathogens. They develop a particularly good activity against parasitic fungi on above-ground parts of plants.

As plant protection agents, the active compounds according to the invention can be used with particularly good success for combating species of Venturia, for example against the apple scab causative organism (Fusicladium dendriticum). and species of Uromyces, such as, for example, the bean rust causative organism (Uromyces phaseoli)» and for combating species of Phytophthora and cereal diseases.

As plant protection agents, the active compounds according to the invention can be used for the treatment of seed or soil and for the treatment of above-ground parts of plants.

The active compounds can be converted into the customary formulations, such as solutions, emulsions, wettable powders, suspensions, powders, dusting agents, foams, pastes, soluble powders, granules, aerosols, suspension-emulsion concentrates, seed-treatment powders, natural and synthetic materials impregnated with active compound, very fine capsules in polymeric substances, coating compositions for use on seed, and formulations used with burning equipment, such as fumigating cartridges, fumigating cans and fumigating coils, as well as ULV cold mist and warm mist formulations.

These formulations may be produced in known manner, for example by mixing the active compounds with extenders, that is to say liquid or liquefied gaseous or solid diluents or carriers, optionally with the use of surface-active agents, that is to say emulsifying agents and/or dispersing agents and/or foam-forming agents. In the case of the use of water as an extender, organic solvents can, for example, also be used as auxiliary solvents.

As liquid solvents diluents or carriers, especially solvents, there are suitable in the main, aromatic hydrocarbons, such as xylene, toluene or alkyl naphthalenes,

Le

A 18 620 ־ 9 chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzenes, chloroethylenes or methylene chloride, aliphatic or alicyclic hydrocarbons, such as cyclohexane or paraffins, for example mineral oil fractions, alcohols, such as butanol or glycol as well as their ethers and esters, ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, or strongly polar solvents, such as dimethylformamide and dimethylsulphoxide, as well as water.

By liquefied gaseous diluents or carriers are meant liquids which would be gaseous at normal temperature and under normal pressure, for example aerosol propellants, such as halogenated hydrocarbons as well as butane, propane, nitrogen and carbon dioxide.

As solid carriers there may be used ground natural minerals, such as kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, and ground synthetic minerals, such as highly-dispersed silicic acid, alumina and silicates. As solid carriers for granules there may be used crushed and fractionated natural rocks such as calcite, marble, pumice, sepiolite and dolomite, as well as synthetic granules of inorganic and organic meals, and granules of organic material such as sawdust, coconut shells, maize cobs and tobacco stalks.

As emulsifying and/or foam-forming agents there may be used non-ionic and anionic emulsifiers, such as polyoxyethylene-fatty acid esters, polyoxyethylenefatty alcohol ethers, for example alkylaryl polyglycol ethers, alkyl sulphonates, alkyl sulphates, aryl sulphonates as well as albumin hydrolysis products. Dispersing agents include, for example, lignin sulphite waste liquors and methylcellulose.

Adhesives such as carboxymethylcellulose and natural and synthetic polymers in the form of powders, granules or latices, such as gum arabic, polyvinyl alcohol and polyvinyl acetate, can be used in the formulations.

Le

A 18 62θ

It is possible to use colorants such as inorganic pigments, for example iron oxide, titanium oxide and Prussian Blue, and organic dyestuffs, such as alizarin dyestuffs, azo dyestuffs or metal phthalocyanine dyestuffs, and trace nutrients, such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.

The formulations in general contain from 0.1 to 95 per cent by weight of active compound, preferably from 0.5 to 90 per cent by weight.

The active compounds according to the invention can be present in the formulations as a mixture with other active compounds, such as fungicides, insecticides, acaricides, nematicides, herbicides, bird repellants, growth factors, plant nutrients and agents for improving soil structure.

The active compounds can be used as such, as their formulations or as the use forms prepared therefrom by further dilution, such as ready-to-use solutions, emulsions, suspensions, powders, pastes and granules. They may be used in the customary manner, for example by watering, spraying, atomising, dusting, scattering, dry dressing, moist dressing, wet dressing, slurry dressing or encrusting.

Especially when used as leaf fungicides, the active compound concentrations in the use forms can be varied within a substantial range. They are, in general, from 0.1 to 0.00001 per cent by weight, preferably from 0.05 to 0.0001?.

In the treatment of seed, amounts of active compound of 0.001 to 50 g, preferably 0.01 to 10 g, are generally employed per kilogram of seed.

For the treatment of soil, amounts of active compound of 1 to 1000 g, in particular 10 to 200 g, are generally employed per cubic metre of soil.

The present invention also provides a fungicidal composition containing as active ingredient a compound of the present invention in admixture with a solid or liquefied gaseous diluent or carrier or in admixture with a liquid diluent or carrier containing a surfaceLe

A 18 620 active agent.

The present invention also provides a method of combating fungi which comprises applying to the fungi, or to a habitat thereof, a compound of the present invention alone or in the form of a composition containing as active ingredient a compound of the present invention in admixture with a diluent or carrier.

The present invention further provides crops protected from damage by fungi by being grown in areas in which immediately prior to and/or during the time of the growing a compound of the present invention was applied alone or in admixture with a diluent or carrier.

It will be seen that the usual methods of providing a harvested crop may be improved by the present invention.

The fungicidal activity of the compounds of this invention is illustrated by the following biotest Examples.

In these Examples, the compounds according to the present invention are each identified by the number (given in brackets) of the corresponding preparative Example, which will be found later in this specification. Example A Fusicladium test (apple)/protective Solvent: 4.7 parts by weight of acetone

Emulsifier: 0.3 part by weight of alkylaryl polyglycol ether

Water: 95 parts by weight

The amount of active compound required for the desired concentration of the active compound in the spray liquid was mixed with the stated amount of solvent, and the concentrate was diluted with the stated amount of water which contained the stated amount of emulsifier.

Young apple seedlings in the 4-6 leaf stage were sprayed with the spray liquid until dripping wet. The plants remained in a greenhouse for 24 hours at 20 degrees C and at a relative atmospheric humidity of 70Ϊ. They were then inoculated with an aqueous conidium suspension of the apple scab causative organism (Fusicladium dendriticum) and incubated for 18 hours in a humidity chamber at

Le

A 18 620

18-20 degrees C and at a relative atmospheric humidity of 100%.

The plants were then brought into a greenhouse again for 14 days.

15 days after inoculation, the infection of the seedlings was determined. The assessment data were converted to percent infection. 0% meant no infection; 100% meant that the plants were totally infected .

In this test, as shown, for example, in the following table compounds (1), (2), (8), (16) and (17) exhibited a very good action which was distinctly superior to that of the compounds known from * the prior art.

Table A Fusicladium test (apple)/ protective

Active compound

Infection in % at active compoundconcentration of 0.0025 %

<img file="IL56378A_D0008.tif" />

(known) 1

<td> (2)</td><td> B-Form</td><td> 50</td>

<td> (8)</td><td> B-Form</td><td> 45</td>

<td> (1)</td><td> A-Form</td><td> 7</td>

<td> (16)</td><td> x HC1</td><td> 9</td>

<td> (17)</td><td> X HC1</td><td> 36</td>

Example Β

Uromyces test (bean rust)/protective

Solvent: 4.7 parts by weight of acetone,

Emulsifier: O.J part by weight of alkylaryl polyglycol ether

Water: 95 parts by weight

The amount of active compound required for the desired 20 concentration of active compound in the spray liquor was mixed with the stated amount of the solvent and the concentrate was diluted with the stated amount of water which contained the stated amount of emulsifier«

The young bean plants, which were in the 2-leaf 25 stage, were sprayed with the spray liquor until dripping wet. The plants remained in a greenhouse for 24 hours at 20-22 deg.C and a relative atmospheric humidity of 70% in order to dry. They were then inoculated with an aqueous uredospore suspension of the causative organism of bean rust (Uromyces phaseoli) and incubated for 24 hours in a dark humidity chamber at 20 - 22 deg.C and 100% relative atmospheric humidity.

The plants were then set up in a greenhouse under intensive illumination for 9 days at 20 - 22 deg.C and 35 a relative atmospheric humidity of ?0-80%.

days after the inoculation, the infection of the plants was determined. The assessment data were converted to % infection. 0% denoted no infection and

100% denoted that the plants were completely infected.

In this test, as shown for example, in the following table compounds (1), (2), (3), (4), (5), (6), (7), (8), (9), W, (11), (13), (14), (15), (16) and (17), exhibited a very good action which was distinctly superior to that of the compounds knewn from the prior art.

aTable B

Urornyces test / protective

Active compound

Infection in % at active compoundconcentraition of 0.005 %

<td colspan="2"> 0-eo-oj 0׳ /S .. ו y___(known) J . i</td><td> 66</td>

<td> (2)</td><td> B-Form</td><td> 37</td>

<td> (3)</td><td> B-Form</td><td> 46</td>

<td> (4)</td><td> B-Form</td><td> 37</td>

<td> (5)</td><td> A-Form</td><td> 37</td>

<td> (6)</td><td> A-Form</td><td> 50</td>

<td> (7)</td><td> A-Form</td><td> 46</td>

<td> (8)</td><td> B-Form</td><td> 50</td>

<td> (1)</td><td> A-Form</td><td> 0</td>

<td> (9)</td><td> B-Form</td><td> 50</td>

<td> \ /</td><td></td><td> 5^*</td>

<td> (״)</td><td></td><td> 54</td>

<td> (13)</td><td></td><td> 0</td>

<td> (14)</td><td></td><td> 62</td>

<td> (15)</td><td></td><td> 59</td>

<td> (16)</td><td> x HC1</td><td> 0</td>

<td> (17)</td><td> x HC1</td><td>³⁵</td>

bExample C

Phytophthora test (tomato)/protective

Solvent: 4.7 parts by weight of acetone

Emulsifier: 0.3 part by weight of alkylaryl polyglycol ether

Water: 95 parts by weight

The amount of the active compound required for the desired concentration of the active compound in the spray liquid was mixed with the stated amount of solvent and the concentrate was diluted with the stated amount of water which contained the stated additions.

Young tomato plants with 2 ’to 4 foliage leaves were sprayed with the spray liquid until dripping wet. .!

The plants remained in a greenhouse for 24 hours at 20 deg.C and at a relative atmospheric humidity of 70%.

The tomato plants were then inoculated with an aqueous spore suspension of Phytophthora infestans. The plants were brought into a moist chamber with an atmospheric humidity of 100% and a temperature of 18-20 deg.C.

After 5 days the infection of the tomato plants was determined. The assessment data were converted to percent infection: 0% meant no infectionj 100% meant that the plants were totally infected.

In this test, as shown for example, in the following table compounds (1), (5), (8), (16) and (17) exhibited a very good action which was distinctly superior to that of the compounds known from the prior art.

I .

c Table C

<td> Phytcphthora test (tomato) /</td><td> protective</td>

<td></td><td> Infection in % at</td>

<td> Active compound</td><td> active compoundconcentration of</td>

0.0025 %

<img file="IL56378A_D0009.tif" />

ce׳ (bO־° ־^CH.

A

M _י ״ (known) (5) A-Form (8) B-Form (1) A-Form (16) x HC1 (7י) x HC1

- 56378/2

Preparative

Example 1

<img file="IL56378A_D0010.tif" />

- CO - NH I

-CH - CH - C(CH_a)₃

CH,

-ס - CHj (!)

<img file="IL56378A_D0011.tif" />

Process variant (a)

505 g (1.5 moles) of l-(4-biphenylyloxy)-3,3-dimethyll-(l,24_״-triazol-l-yl)-butan-2-ol (A form) and 140 g (1.6 moles) of methoxymethyl isocyanate were heated under reflux in 2.5 litres of tetrahydrofuran in the presence of 40 ml of triethylamine and 1 ml of dibutyl-tin dilaurate for 48 hours. Thereafter, the solvent was stripped off in vacuo and 3 litres of petroleum ether were added to the residue.

The crystalline precipitate formed was extracted by stirring with 1.5 litres of diisopropyl ether. 528 g (82.5? of theory) of l-(4-biphenylyloxy)3,3־”dimethyl-2-methoxymethylcarbamoyloxy-l-(l,24_״-triazol-l-yl)-butane (A form) of melting point 9598°־C were obtained.

The compounds of Table 1 which follows were obtained analogously.

Table 1

<img file="IL56378A_D0012.tif" />

- CO - NKR I

CH - C(CH_S )_s ־ 15 Example X

No.

Melting point (°C)

ΪΘ

<img file="IL56378A_D0013.tif" />

<img file="IL56378A_D0014.tif" />

<img file="IL56378A_D0015.tif" />

-(CH,), -Cl -CO-OCHj -C0-0C₈H5 -(ch₈)₂ -Cl -CO-OCH_S-C0-0C₂H₅-CHj -O-CH_S

-CO-N-SOjCH_S 'ch₂-ch=ch₂

138-41 (B-Form) 184-85 (B-Form) 164-66 (B-Form) 103-05 (A-Form) 120 (A-Form) 100 (A-Form) 141-44 (B-Form) 141-44 (B-Form)

40¾ )¾ -CH(CH₃ )-^¾ 109-15 (B-Form) W, © 194-200 ^CH־CH-C00CH₃

<img file="IL56378A_D0016.tif" />

<img file="IL56378A_D0017.tif" />

-ΟΗ,-Ο-Ο,Η,

¾¢-0-,(,01)- ©־*

158-65

193-206

148-55

151-54 (A-Form)

140(xHC1) (Base , _x 115°C) lOO(xHCl)

NOTE:

A form and B form = in each case one of the two possible geometric isomers.