HU208235B - Fungicidal compositions comprising thiazole derivative as active ingredient, process for producing the active ingredients and for using the composition - Google Patents

Abstract

Triazole derivatives of formula (I) are new. or an acid addn. salt or metal salt complex of (I) R = opt. substd. phenyl; A = C=O, C=N-OR' where R1 = H, opt. substd. alkyl, alkenyl, or aralkyl; gp (i) or (i) R2 = H, halogen, alkyl, haloalkyl, alkylthio, OH, CN, NO2, NH2, alkylamino or dialkylamino.

Description

A is a carbonyl group, -C = N-OR ^1, or a group of formula (a) wherein R ¹ is C 1 -C 10 alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, (3-6) C 1 -C 3 cycloalkyl) C 1 -C 3 alkyl or phenyl (C 1 -C 3 alkyl) optionally substituted on the phenyl moiety by one or two halogen atoms;

R ¹ 'is hydrogen or C 1-6 alkyl.

\\

Nch ₂ -ar (I)

0-n /

(the)

HU 208 235 B

Description: 16 pages (including 3 pages)

HU 208 235 Β

FIELD OF THE INVENTION The present invention relates to a fungicidal composition comprising a thiazole derivative of formula (I) as an active ingredient, and to a process for the preparation and use of the active ingredient.

In the general formula (I)

R is phenyl substituted with one or two halogens,

I

A is a carbonyl group, -C = N-OR *, or a group of the formula (a) wherein R ¹ is C 1-10 alkyl, C 3-6 alkenyl, C 3-6 alkynyl, (3-6) C 1 -C 3 cycloalkyl-C 1 -C 3 alkyl or phenyl (C 1 -C 3) alkyl optionally substituted on the phenyl moiety by one or two halogens;

R ¹ 'is hydrogen or C 1-6 alkyl.

The technical background of the present invention is provided by

European Patent Applications A-0007678, A-O296673 and A-0216424.

EP-A-0007678 discloses an oxime derivative of formula A wherein Sev is a monocyclic heteroaromatic group having 2 heteroatoms, at least one of which is N, Ar is phenyl or a 5 or 6 membered monocyclic heteroaromatic. group. R 1 is alkyl, alkenyl, alkynyl, cyanoalkyl, ureaalkyl or aminoalkyl, m and n are both 0 or 1 and m + n is not an integer other than 2; also included are N-oxide derivatives of the compounds. These known compounds have an anti-ulcer effect in the gastrointestinal tract of mammals.

EP-A-0296673 discloses thiazocarboxamide derivatives of the general formula (B) wherein R ₂ is an optionally substituted aryl; R ₃ is hydrogen or optionally substituted alkyl, alkenyl or alkynyl; R ₄ is hydrogen or halogen, and is alkyl, haloalkyl, alkoxy, haloalkoxy, alkylthio, hydroxy, cyano, nitro, amino, alkylamino, dialkylamino or morpholino. ; X is oxygen or sulfur, carbonyl or -CR ₈ R ₉ wherein R ₈ and R ₉ are each independently hydrogen or alkoxy; Y is oxygen or sulfur, nj is an integer from 0 to 6, πη is 0 or 1, Z is phenyl; the scope also includes acid addition salts and metal salt complexes. The compounds of formula (B) exhibit antifungal activity.

EP-A-0216424 discloses imidazole derivatives of the general formula (C); those wherein _R5 is optionally substituted phenyl, R ₆ is an optionally substituted alkyl, cycloalkyl, alkenyl, aryl or aralkyl; R ₇ is hydrogen, cyano, -CONH ₂ , or optionally substituted alkyl; X! is oxygen or = NOR ₁₀ wherein R ₁₀ is hydrogen or optionally substituted alkyl, cycloalkyl, alkenyl, alkylcarbonyl, aryl or aralkyl; acidic addition salts of compounds of formula (C) are also included. The compounds of formula (C) show fungicidal activity.

The alkyl or alkenyl groups in the substituents of the compounds of formula I are straight or branched C 1 -C 10 and C 3 -C 6, preferably C 1 -C 8 and C 3 -C 6, respectively.

Preferably the substituent optionally present is one or more commonly used substituents which are favorable for the structure / activity, potency, absorption or other properties of the pesticidal compounds. Halogen may be substituted.

When the above substituents contain an allyl group, it is preferably a straight or branched alkyl group having from 1 to 10 carbon atoms, more preferably from 1 to 6 carbon atoms, most preferably from 1 to 4 carbon atoms. Cycloalkyl groups preferably contain from 3 to 6 carbon atoms.

In the compounds of formula (I), R is preferably phenyl having from 1 to 2 halogens, preferably fluorine or chlorine.

R ¹ is preferably C 1 -C 10 alkyl, more preferably C 1 -C 8 alkyl, C 3 -C 6 alkenyl, preferably C 3 -C 4 alkenyl, or benzyl; the latter group may optionally carry one or two halogens.

Particularly preferred compounds of formula I are those wherein R is fluorophenyl or dichlorophenyl; R ¹ is methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, cyclopropylmethyl, allyl, benzyl, chlorobenzyl, dichlorobenzyl or bromobenzyl group.

It should be noted that compounds of formula I wherein A is

I

-C = N-OR 'may form different geometric isomers, and compounds of formula (I) wherein A is (a) may also have different geometric and optical isomers. These isomers and mixtures of isomers are also within the scope of the present invention.

The compounds of formula (I) are prepared by:

a) for the preparation of compounds of formula I wherein A is a carbonyl group, wherein R is as defined above, a phosphonate derivative of formula II, wherein R is as defined above, R ⁴ , R ⁵ and R ⁶ are as defined above. the same or different C 1-4 alkyl groups

- reacting with a thiazolecarboxaldehyde (III) in the presence of a base and

(b) in place of A

I

For the preparation of compounds of formula I having the formula -C = N-OR ', wherein R is as defined above, if desired, the compounds of formula I obtained by process a) with a hydroxylamine derivative of formula IV

R ¹ has the same meaning as defined above

235 Β or the acid addition salt of this compound and then

c) for preparing compounds of formula (I) containing a group of formula in the formula (a) - wherein R and ^R1 'is as defined above - if desired, salifying the procedure a) (I) Compounds of formula (V) alkanediol of the formula - is reacted with Lewis acid in the presence of: - wherein ^R1 'is as defined above.

Particularly preferred are compounds of formula II wherein R ⁴ and R ⁶ are both ethyl and R ⁵ is methyl.

The base used in step (a) is lithium diisopropylamide, potassium tert-butoxide, sodium hydride or most preferably butyllithium.

Step (a) is preferably carried out in the presence of a solvent. The solvent may be dimethylformamide, dimethylsulfoxide or ethers, preferably tetrahydrofuran. The reaction is conveniently carried out at a temperature of from -100 ° C to 100 ° C, preferably from -80 ° C to 70 ° C.

When the compound of formula IV is used in step b), the compound is conveniently prepared in situ. When an acid addition salt of a compound of formula (IV) is used, the reaction is conveniently carried out in the presence of a base such as sodium acetate.

Step b) is conveniently carried out in the presence of a solvent; as solvent, dimethylformamide, dimethylsulfoxide, ethers such as tetrahydrofuran, aromatic compounds and alcohols, preferably methanol or ethanol. The reaction is conveniently carried out at a temperature of 0 ° C to 100 ° C, preferably 15 ° C to 80 ° C.

In step c), the preferred Lewis acid is chloro-trimethylsilane, iodo-trimethylsilane or a mixture of the two. A protonic acid such as para-toluenesulfonic acid or methanesulfonic acid may also be present.

Step c) is carried out in the presence of an inert solvent; aromatic compounds such as xylene. Alternatively, an excess of the compound of formula (V) serves as a solvent.

The reaction is conveniently carried out at a temperature between 0 'C and 170' C, or more preferably between 15 'C and 150' C.

Compounds of formula II are prepared as described in Burkhouse, D. and Zimmer, H. Synthesis, 330, 1984. Compounds of formula (III) containing substituents other than R ² alkyl are prepared by reacting thiourea with 2-bromo-1,3-propanediol and treating the resulting 2-aminothiazole carboxaldehyde hydrobromide with amyl nitrite. Compounds of formula (III) wherein R ² is alkyl are prepared by reacting an appropriately substituted alkylthioamide with 2-bromo-1,3-propanedal analogous to that described above. 2-Bromo-1,3-propane diate can be prepared as described in the literature [Trofimenko, S., J. Org. Chem. 28, 3243 (1963)].

The compounds of formula (IV) and (V) are known and can be prepared by known methods.

The compounds of formula (I) show fungicidal activity; in addition, it has been found that some of the compounds of formula I also have a vapor effect. The present invention also relates to fungicidal compositions containing the compounds of formula (I) as active ingredients. The compounds of formula (I) are formulated with at least one carrier to form fungicidal compositions. The compositions comprise at least one compound of the invention or mixtures of several compounds. The invention also relates to the use of isomers and mixtures of isomers in compositions; it is to be noted that the various isomers or mixtures of isomers may have different activity levels or spectrum of activity.

The compositions of the present invention contain from 0.5 to 95% by weight of the active ingredient.

The function of the excipients and carriers is to facilitate the application of the active ingredient to the treated plants, seeds or soil. The excipients ensure proper storage, transport and handling of the preparation. Solid or liquid materials are used as excipients. It is also possible to use materials which are gaseous at normal temperature and pressure but which become liquid under pressure. Any of the commonly used excipients and carriers can be used in the compositions.

Solid excipients include natural and synthetic clays and silicates, such as natural silicates such as diatomaceous earth; magnesium silicates such as talc; magnesium aluminum silicates, such as attapulgite or vermiculite; aluminum silicates, such as kaolinite, montmorillonite or mica; calcium carbonate; calcium sulphate; ammonium sulphate; synthetic hydrated silicon oxides and synthetic calcium or aluminum silicates; elements such as carbon or sulfur; natural or synthetic resins such as coumarone resin, polyvinyl chloride, styrene polymers and copolymers; solid polychlorophenols; bitumen; waxes such as beeswax, paraffin wax, chlorinated mineral waxes; solid fertilizers such as superphosphate.

Liquid excipients include water; alcohols such as isopropanol or glycols; ketones; such as acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone; ethers; aromatic or araliphatic hydrocarbons such as benzene, toluene or xylene; kerosene fractions such as kerosene or light mineral oil; chlorinated hydrocarbons such as carbon tetrachloride, perchlorethylene or trichloroethane. In some cases, it is preferable to use a mixture of these liquids.

Fungicidal compositions are often formulated and supplied in concentrated form and diluted immediately before use. The dilution process is facilitated by the presence of a small amount of excipient, such as a surfactant. At least one of the excipients in the composition is preferably a surfactant. so for example

The composition may contain at least two excipients, one of which is at least a surfactant.

The surfactant may be an emulsifier, dispersant or wetting agent; it may be nonionic or ionic. Suitable surfactants include sodium or calcium salts of polyacrylic acid and lignin sulfonic acids. The surfactant may include condensation products of ethylene oxide and / or propylene oxide with fatty acids or aliphatic amines or amides having at least 12 carbon atoms; fatty acid esters of glycerol, sorbitol, sucrose or pentaerythrol; condensation products thereof with ethylene oxide and / or propylene oxide; and condensation products of fatty alcohols or alkyl phenols such as p-octylphenol or p-octylcresol with ethylene oxide and / or propylene oxide; sulphates or sulphonates of these condensation products; alkali metal or alkaline earth metal salts of sulfonic acids or sulfates, preferably sodium salts, wherein the sulfonic acid esters contain at least 10 carbon atoms, such as sodium lauryl sulfate, sodium sec alkyl sulfates; sodium salts of sulfonated castor oil, sodium alkylaryl sulfonates such as dodecylbenzene sulfonates; and ethylene oxide and polymers are copolymers of ethylene oxide and propylene oxide.

The compositions of the invention may be formulated as wettable powders, powders, granules, solutions, emulsifiable concentrates, emulsions, suspension concentrates or aerosols. Wettable powders will generally contain 25, 50 or 75% by weight of active ingredient, and 3 to 10% by weight of solid, inert excipient and, if necessary, 0-10% of a stabilizer and / or other excipients such as absorption aids or they contain an adhesive. Powders are generally prepared as powder concentrates; they have the same composition as wettable powders, but do not contain a dispersant; the powders are diluted with a solid vehicle just prior to use to form a formulation containing 0.5 to 10% by weight of the active ingredient and sprayed. The granules generally have a size between 1.676 and 0.152 mm. The granules are prepared by agglomeration or impregnation. Generally, the granules will contain 0.5 to 75% by weight of active ingredient, as well as 0 to 10% by weight of additives such as stabilizer, surfactant, slow release agent, binder. The so-called "dry rolling powders" consist of granules of relatively small particle size, which exhibit relatively high concentrations of the active ingredient. Generally, emulsifiable concentrates may contain from 1 to 50% w / v of the active ingredient, 2 to 20% w / v of the emulsifier and 0 to 20% w / v of other additives, such as a stabilizer, absorption aid or corrosion inhibitor, in addition to the solvent and, if necessary. They contain. Suspension concentrates are generally formulated to form a stable, non-sedimenting liquid composition; in this case, the active ingredient is generally present in an amount of from 10 to 75% by weight, in addition to 0.5 to 15% by weight of a dispersing agent, 0.1 to 10% by weight of a suspending agent such as a protective colloid or thixotropic agent; Thus, an antifoam, corrosion inhibitor, stabilizer, absorption enhancer, tackifier, and organic liquid or water in which the active ingredient is substantially insoluble are used; organic solids or inorganic salts may also be used, in addition to inhibit sedimentation in the compositions or as antifreeze.

Aqueous dispersions and emulsions may be prepared by diluting wettable powders or a concentrate with water; these compositions also form part of the invention. The emulsions may be of the water-in-oil or oil-in-water type; their consistency may be dense, mayonnaise-like.

The compositions may also be mixed with other herbicidal, insecticidal or fungicidal active ingredients.

Auxiliaries are preferably used which provide slow release of fungicidal compounds into the environment and into plants. Slow release formulations may be applied to soil close to the roots, e.g., grape seedlings; furthermore, the composition may comprise an adhesive, which enables application directly to the strain of the vine.

The present invention also relates to the use of a fungicidal composition comprising a compound of formula (I), which comprises treating the fungi, wherein the fungus is produced, the plants, the seeds or their environment.

The invention relates to the use of the compositions of the invention against fungi; preferably, grapes, cereals, wheat, barley, rice or tomatoes may be protected against fungal damage. The time of protection generally depends on the compound chosen and other external factors, such as the climate, however, the effect of which may be reduced by a properly formulated formulation.

The following examples illustrate the present invention.

/. example

Preparation of J - (2,4-Dichlorophenyl) -2- (5-thiazolyl) ethanone (R = 2,4-Dichlorophenyl)

I

A = C = O) ¹

i) Preparation of 5-Thiazolecarboxaldehyde Thiourea (g, 0.44 mol) was added to a solution of 2-bromo-1,3-propanediol (66 g, 0.44 mol) in acetone (1 L). The resulting mixture was stirred vigorously for 1 hour under reflux. The mixture was then cooled to room temperature and the solid product was collected by filtration and dried to give 85 g of 2-aminothiazole-5-carboxaldehyde hydrobromic acid as a yellow solid. Mp 126 ° C.

A solution of 2-aminothiazole-5-carboxaldehyde hydrobromide (g) (0.168 mmol) in methanol was neutralized with sodium methoxide (9 g, 0.168 mol). The methanol is then distilled off under reduced pressure, and the resulting solid is suspended in 200 ml of tetrahydrofuran and added slowly to a boiling solution under reflux; it contains 31 g of amyl nitrite in 300 ml

Dissolved in tetrahydrofuran. The resulting mixture was then refluxed for 1 hour, cooled, filtered and then concentrated under reduced pressure. Diethyl ether (400 mL) was added to the residue, and the mixture was stirred for 1 hour, filtered and concentrated. The residue is then chromatographed on silica gel, eluting with 2: 1 petroleum ether: diethyl ether. 4.4 g of 5-thiazolecarboxaldehyde are thus obtained in the form of a yellow solid. Mp .: 15 'C.

ii) Preparation of 1- (2,4-Dichlorophenyl) -2- (5-thiazolyl) ethanone A solution of butyl lithium in hexane (2.5 M) was added dropwise to 12.8 g (39 mmol) (2.4 -dichlorophenyl) methoxymethylphosphonate in 150 ml of tetrahydrofuran at -78 ° C under a nitrogen atmosphere. A dark red solution was obtained, which was stirred for 10 minutes, to which was added a solution of 5-thiazolecarboxaldehyde (3.7 g, 32 mmol) in tetrahydrofuran (50 mL) (product from (i)). After a further 1 hour at -78 ° C, the mixture was allowed to warm to room temperature, treated with water, acidified with 35 ml of concentrated sulfuric acid and then refluxed for 20 hours. The mixture was cooled, tetrahydrofuran was distilled off, the aqueous residue was neutralized with sodium carbonate and extracted with ethyl acetate (2 x 200 mL). The combined organic extracts were washed with brine, dried and concentrated. The residue was chromatographed on silica eluting with petroleum ether / ethyl acetate (7: 3). 5.75 g of 1- (2,4-dichlorophenyl) -2- (5-thiazolyl) ethanone are obtained in the form of a pale yellow solid.

Mp: 75-77 ° C.

ANALYSIS:

Calculated: C, 48.5; H, 2.6; N, 5.1;

Found: C, 47.9; H, 2.6; N, 5.0.

Example 2 Preparation of 1- (2,4-Dichlorophenyl) -2- (5-thiazolyl) ethanone-O-ethyloxime

I (R = 2,4-dichlorophenyl); A = C = N-ORf I / R = ethyl

1.1 g (4 mmol) of 1- (2,4-dichlorophenyl) -2- (5-thiazolyl) ethanone (prepared in Example 1), 1.64 g (20 mmol) of sodium acetate, and 1.95 g (20 mmol) of O-ethylhydroxylamine hydrochloride in 80 ml of methanol are heated under reflux for 20 hours under nitrogen. The mixture was cooled to room temperature, water (50 mL) was added and the reaction mixture was concentrated under reduced pressure. The aqueous residue was made basic with sodium carbonate and extracted with ethyl acetate (2 x 200 mL). The combined organic extracts were washed with brine, dried, and concentrated. The residue is chromatographed on silica, eluting with a 4: 1 by volume mixture of petroleum ether (fraction 40-60) and ethyl acetate. 0.88 g of compound A (E-isomer) and 0.20 g of compound B (Z-isomer) are thus obtained in the form of an oily product. Both compounds are 1- (2,4-dichlorophenyl) -2- (5-thiazolyl) ethanone-O-ethyl oxime.

Analysis: Calculated for E / Z: C, 49.5; H, 3.8; N, 8.8;

Found: C, 51.0; H, 4.3; N, 8.4.

Example 3

2- (2,4-dichlorophenyl) -2- (thiazol-5-ylmethyl) -1,3-dioxolane [R = 2,4-dichlorophenyl;

R ^{1 is} hydrogen;

Group A - (a)]

1.49 g (5.4 mmol) of 1- (2,4-dichlorophenyl) -2- (5-thiazolyl) ethanone (prepared in Example 1) were treated with 2.8 ml of chlorotrimethylsilane in 25 ml of ethane. 1,2-diol; the mixture was stirred at 90 ° C for 4 hours, then cooled to room temperature. The reaction mixture was poured into sodium bicarbonate solution and extracted with ethyl acetate. The organic extract was washed with water and dried over magnesium sulfate. The solvent was distilled off under reduced pressure to give a dark brown oily product which was purified by flash chromatography. For this purpose, a silica gel column and a 1: 9 by volume mixture of ethyl acetate and petroleum ether (fractions 60-80) were used. 0.64 g of 2- (2,4-dichlorophenyl) -2- (thiazol-5-ylmethyl) -1,3-dioxolane is obtained in the form of a yellow oil. ANALYSIS:

Calculated: C, 49.5; H, 3.8; N, 4.4;

Found: C, 51.2; H, -4.3; N, 4.3.

Example 4

Preparation of 2- (2,4-dichlorophenyl) -2- (thiazol-5-ylmethyl) -4-methyl-1,3-dioxolane [R = 2,4-dichlorophenyl; R ¹ = methyl);

A = group of formula (a)]

1.3 g (11 mmol) of 1- (2,4-dichlorophenyl) -2- (5-thiazolyl) ethanone (prepared according to Example 1), 6 ml of chlorotriomethylsilane and 2 ml of iodomethylsilane propane-1,2-diol. The mixture was stirred at 110 ° C for 4 hours and then cooled to room temperature. The reaction mixture was poured into sodium bicarbonate solution and extracted with ethyl acetate; the organic phase is washed with water and dried over magnesium sulfate. The solvent was distilled off under reduced pressure to give a dark brown oily product, which was purified by flash column chromatography on silica gel. Elution was carried out with a 5: 95 by volume mixture of diethyl ether and dichloromethane. 1.89 g of 2- (2,4-dichlorophenyl) -2- (thiazol-5'-ylmethyl) -4-methyl-1,3-dioxolane are obtained in the form of a mixture of isomers. The resulting material was purified by flash chromatography again using a silica gel column and ethyl acetate / petroleum ether (60-80) (1: 9) to give two enantiomeric pairs, designated as Sample A and B. Sample A contains 0.49 g of (2R, 4R) (2S, 4S) isomer, Sample B contains 0.45 g of (2R, 4S), (2S, 4R) isomer.

M ⁺ calcd: 330.01;

found: Sample A: 330,014 Sample B: 330,013.

HU 208 235 Β

Example 5

Preparation of 2- (4-fluorophenyl) -2- (thiazol-5-ylmethyl) -4-methyldiphenoxolane [R = 4-fluorophenyl; R ^{1 is} methyl;

A = group of formula (a)]

0.75 g (3.3 mmol) of 1- (4-fluorophenyl) -2- (5-thiazolyl) ethanone (prepared as in Example 1), 2 ml of propane-1,2-diol and 0 5 ml of methanesulfonic acid are mixed with 30 ml of xylene. The mixture was heated under reflux under nitrogen for 2 hours, using a Dean Stark plug, and then cooled to room temperature. The reaction mixture was poured into water, extracted with ethyl acetate, and dried over magnesium sulfate. The solvent was distilled off under reduced pressure to give a dark brown oily product, which was purified by flash column chromatography on silica gel. Elution was carried out with a 2: 8 by volume mixture of ethyl acetate and petroleum ether (6080). This gives two enantiomeric pairs of 2- (4-fluorophenyl) -2- (thiazol-5-ylmethyl) -4-methyl-1,3-dioxolane. Sample A contained 0.17 g of (2R, 4R) (2S, 4S) isomer and Sample B contained 0.11 g of (2R, 4S) (2S, 4R) isomer as an oily product. Analysis (mixture of compounds A and B):

Calculated: C, 60.2; H, 5.0; N, 5.0;

Found: C, 61.5; H, 5.9; N, 4.6.

6-35. example

1-5. The compounds of Table I can be prepared by the same procedure as described in Example II. Mass spectral data and analytical data for these compounds are shown in Table IA.

Table I

Example number isomer R THE R ¹ 6 - 4-fluorophenyl 1 -C = O - 7 - 4-chlorophenyl 1 -C = O - 8A E 2,4-dichlorophenyl 1 -C = N-OR ¹ -CH ₃ 8B Z 2,4-dichlorophenyl 1 -C = N-OR ¹ -ch ₃ 9A E 2,4-dichlorophenyl 1 -C = N-OR ' -ch ₂ ch ₂ ch ₃ 9B Z 2,4-dichlorophenyl 1 -C = N-OR ¹ -ch ₂ ch ₂ ch ₃ 10A E 2,4-dichlorophenyl 1 -C = N-OR ¹ -CH (CH ₃ ) ₂ 10B Z 2,4-dichlorophenyl 1 -c = n-or ' -CH (C ₃ ) ₂ 11A E 2,4-dichlorophenyl 1 -C = N-OR ' - (CH ₂ ) ₃ CH ₃ 11B Z 2,4-dichlorophenyl 1 -C = N-OR ' - (CH ₂ ) ₃ CH ₃ 12A E 2,4-dichlorophenyl 1 -C = N-OR ' -CH ₂ CH (CH ₃ ) ₂ 12B Z 2,4-dichlorophenyl 1 -c = n-or ' -CH ₂ CH (CH ₃ ) ₂ 13A E 2,4-dichlorophenyl 1 -c = n-or ' KH (CH ₃ ) C ₂ H ₅ ) 13B Z 2,4-dichlorophenyl 1 -C = N-OR ¹ -CH (CH ₃ ) (C ₂ H ₅ ) 14A E 2,4-dichlorophenyl 1 -C = N-OR ¹ - (CH ₂ ) ₄ CH ₃ 14B Z 2,4-dichlorophenyl 1 -C = N-OR ^! - (CH ₂ ) ₄ CH ₃ 15 E 2,4-dichlorophenyl 1 -C = N-OR ¹ - (CH ₂ ) ₅ CH ₃ 16A E 2,4-dichlorophenyl 1 -C = N-OR ¹ - (CH ₂ ) ₆ CH ₃ 16B Z 2,4-dichlorophenyl 1 -C = N-OR ¹ - (CH ₂ ) ₆ CH ₃ 17A E 2,4-dichlorophenyl 1 -C = N-OR * cyclopropylmethyl

HU 208 235 Β

Example number isomer R THE R ¹ 17B Z 2,4-dichlorophenyl 1 -c = n-or ' cyclopropylmethyl 18A E 2,4-dichlorophenyl 1 -C = N-OR ' -CH ₂ CH = CH ₂ 18B Z 2,4-dichlorophenyl 1 -C = N-OR ' -CH ₂ CH = CH ₂ 19A E 2,4-dichlorophenyl 1 -C = N-OR ¹ benzyl 19B Z 2,4-dichlorophenyl 1 -C = N-OR ' benzyl 20A E 2,4-dichlorophenyl 1 -C = N-OR ' 4-chlorobenzyl 20B Z 2,4-dichlorophenyl 1 -C = N-OR ¹ 4-chlorobenzyl 21A E 2,4-dichlorophenyl 1 -C = N-OR ' 2,4-dichlorobenzyl 21B Z 2,4-dichlorophenyl 1 -C = N-OR * 2,4-dichlorobenzyl 22 E 2,4-dichlorophenyl 1 -C = N-OR ' 4-bromobenzyl 23 E 2,4-dichlorophenyl 1 -c = n-or ' -ch ₂ -c = ch 24A E 4-fluorophenyl 1 C = N-OR ' ch ₃ 24B Z 4-fluorophenyl 1 -C = N-OR ' -ch ₃ 25 E 4-fluorophenyl 1 -C = N-OR ¹ -ch ₂ ch ₃ 26A E 4-fluorophenyl 1 -C = N-OR ¹ benzyl 26B Z 4-fluorophenyl 1 -C = N-OR * benzyl 27 E 4-chlorophenyl 1 -C = N-OR * -ch ₃ 28A E 4-chlorophenyl 1 -C = N-OR ' -ch ₂ ch ₃ 28B Z 4-chlorophenyl 1 -C = N-OR ' -ch ₂ ch ₃ 29 E 4-chlorophenyl 1 -C = N-OR ' - (CH 2) ₄ CH ₃ 30A E 4-chlorophenyl 1 -C = N-OR * -ch ₂ -ch = ch ₂ 30B Z 4-chlorophenyl 1 -C = N-OR * -ch ₂ -ch = ch ₂ 31 E 4-chlorophenyl 1 c = n-or ' benzyl 32A (2S.4S) 2,4-dichlorophenyl a group of the formula (a) -ch ₃ 32B (2R.4S) 2,4-dichlorophenyl a group of the formula (a) -ch ₃ 33 (2R, 4R), (2S, 4S) (2R, 4S) & (2S, 4R) 2,4-dichlorophenyl a group of the formula (a) -c ₂ h ₅ 33A (2R, 4R), (2S, 4S) 2,4-dichlorophenyl a group of the formula (a) -c ₂ h ₅ 34 (2R, 4R), (2S, 4S) (2R, 4S) & (2S, 4R) 2,4-dichlorophenyl a group of the formula (a) -ch ₂ ch ₂ ch ₃ 35 4-fluorophenyl (a) General Group 1 h

HU 208 235 Β

Table IA Test data

Example number Op. (° C) M + C H N Song. Found Song. Found Song. Found Song. Found 6 49-50 7 60-62 55.7 55.6 3.4 3.6 5.9 5.9 8A 299.98907 .......... 8B 299.9884 9A ------------------------ 51.1 9B 51.0 4.3 4.4 8.5 8.6 1OA ------------------------ 51.1 10B 51.3 4.2 4.4 8.5 7.4 11A ........................ 52.5 11B 52.9 4.7 4.6 8.2 8.3 12A .......................- 52.5 12B 52.5 4.7 4.8 8.2 8.3 13A ------------------------ 52.5 13B 52.7 4.7 4.8 8.2 8.4

Example number Analysis% M + C H N Song. Found Song. Found Song. Found Song. Found 14A ................... 53.8 14B 53.2 5.1 4.7 7.8 7.9 15 ------------------- 54.9 56.6 5.3 5.4 7.5 7.3 16A ..........-......- - 56.1 16B 56.3 5.7 6.2 7.3 7.2 17A ---- 340,02037 17B 340.02028 18A ---- 326,0047 18B 326.0036 19A ---- 376,0203 19B 376.0196 57.3 59.0 3.7 4.2 7.4 7.4 20A ------------------- 52.5 20B 52.5 3.2 3.2 6.8 6.9 21A - -.....-.........- - 48.4 21B 48.5 2.7 2.7 6.3 6.7 22 ------------------- 47.4 47.4 2.9 3.1 6.1 6.4 23 ---- 324.9970 324.9990 24A ------------------- 57.6 24B 58.0 4.4 4.5 11.2 11.1 25 ------------------- 59.1 59.7 4.9 5.1 10.6 10.0 26A ------------------- 66.3 26B 66.9 4.6 5.1 8.5 8.8 27 ................... 54.1 54.1 4.1 4.5 10.5 10.5

HU 208 235 Β

Example number Analysis% M + C H N Song. Found Song. Found Song. Found Song. Found 28A-.......... 55.7 ........ 28B 55.1 4.6 4.9 10.0 9.8 29 ................... 59.6 59.4 5.9 6.4 8.7 7.9 30A - - -.........-.....- 57.5 30B 57.5 4.5 4.6 9.6 9.3 31 ------------------- 63.5 63.5 3.8 4.1 8.2 7.9 32A - - - - 330,013 32B ---- 330,012 33 ---- 344,0279 33A ---- 344,027 34 ---- 358,0441 35 ------------------- 58.8 60.2 4.6 4.8 5.3 5.5

Example 36

The fungicidal activity of the compounds of the present invention is controlled by the following assays.

(a) Examination of antisspore activity against grapevine Plasmopara viticola; PVA)

The antispore effect is tested by spraying the leaves; grape seedlings (cv Cabemet Sauvignon) are infected 2 days before treatment with test chemical. For the infection, 10 ⁴ zoospores / ml aqueous spore suspension was used. The infected seedlings were kept for 24 hours in high humidity and then for 24 hours in a greenhouse at room temperature and normal humidity. Infected leaves are then sprayed on the back of the leaf with a drug-containing solution. The active ingredient is applied in a 1: 1 water / acetone solution; the aqueous acetone solution contains 0.04% Tween 20 (polyoxyethylene / sorbitan ester; surfactant). Spraying is performed using a moving band sprayer, spraying 1 kg / ha on the plants. After spraying, the seedlings were placed under normal greenhouse conditions for 96 hours; then keeping them in a high humidity space for 24 hours; thus, spore propagation prior to evaluation is promoted. For evaluation, the size of the leaf area infected with the spore is compared to the infected area on the control leaves, and the result is expressed as a percentage.

(b) Direct protection against grape mold (Plasmopara viticola; Pvp)

During the tests, the back of the vine leaves (cv Cabemet Sauvignon) was sprayed with the spray compound containing the test compound at a concentration of 1 kg of active ingredient / hectare; spraying using the apparatus described in (a); spraying the plants under normal greenhouse conditions for 24 hours; infecting the back of the leaves with an aqueous suspension of 10 ⁴ zoospores / ml; the infected plants are kept in high humidity for 24 hours and then in normal greenhouse conditions for 5 days, then returned to high humidity for 24 hours. For evaluation, the size of the spore-covered leaf surface is compared with the spore-covered leaf surface of the control leaves.

(c) Investigation of direct protective effect against gray grape mold

Botrytis cinerea; bcp)

During the test, the leaves of the test plants are sprayed. Spray the back of vine leaves (cv Cabernet Sauvignon) with a 1 kg / ha solution of the test compound using the apparatus described in (a). Twenty-four hours after spraying, the leaves are infected using 10 ⁵ conidia / ml of spore suspension. The plants were kept in high humidity for another 5 days; for evaluation, the area of the infected leaf surface is expressed as a percentage relative to that of the control plants.

(d) Impact study on wheat leaf blotch (Leptosphaeria nodorum; Ln)

The purpose of the tests is to cure already infected leaves. Wheat seedlings (Mardler cv) are infected at the single leaf stage using an aqueous suspension of 1x10 ⁶ spores / ml. The infected plants were kept in high humidity for 24 hours. The plants are then sprayed with a solution containing the test compound; A dose of 1 kg of active ingredient / ha is sprayed using the apparatus described under a). After the spray has dried, the plants are exposed to moderate humidity at 20-25 ° C for 6 to 8 days.

HU 208 235 Β, followed by evaluation. In the evaluation, the density of the lesions on each leaf is compared to the lesion on the leaves of control plants.

(e) Impact study on barley powder mold (Erysiphe graminis f. sp. hordei; Eg)

The purpose of the test is to check the healing effect. The tests are performed by spraying the leaves. Barley seedlings (cv. Golden Promise) are infected using conidia powder of Erysiphe graminis. The infected plants were kept overnight in a room-temperature greenhouse with normal humidity. The seedlings are then sprayed with a spray liquid containing the test compound at a dose of 1 kg of active ingredient / hectare. For spraying the

the equipment referred to in point (a) is used. After the leaves have dried, the plants are returned to a medium-humid environment at 20-25 ° C for 7 days and then evaluated. The evaluation is based on a comparison of the leaf area of the spore covered with the infected leaf area of the control plants.

(f) Impact study on cereal brown rust (Puccinia recondita; Pr)

The protection test is performed by spraying leaves; cereal seedlings (cv Brigand) are grown to the stage of 1-1 1/2 leaves. The seedlings are then sprayed with the test compounds at a dose of 1 kg / ha using the apparatus mentioned under (a). Test compounds are applied as a solution or suspension in a 50:50 solution / suspension of acetone / water containing 0.04% Tween 20.

After 18-24 hours after treatment, the seedlings are infected with an aqueous suspension of 10 ⁵ spores / ml. The seedlings are sprayed from all sides. For 18 hours after infection, the plants were kept in a high humidity room at 20-22 ° C, then in a room temperature greenhouse with a medium relative humidity room at 20 ° C.

Infection evaluation is performed 10 days after infection, when rusty plants are compared to rusting on control plants.

(g) Examination of the effect on rice leaf thistle (Pyricularia oryzae Po)

The test is to control the therapeutic effect by spraying leaves. Leaves of rice seedlings (about 30 seedlings / container) were sprayed with an aqueous suspension of 10 ⁵ spores / ml 20-24 hours prior to treatment with test compounds. The infected seedlings are kept overnight in a high humidity space and the leaves are allowed to dry. Spray broth containing the test compound is then applied at a dose of 1 kg of active ingredient / hectare using the apparatus described in (a). The seedlings are then kept in a high humidity space at 25-30 ° C; 45 days after treatment. The leaves are compared to control plants and the density of necrotic lesions per leaf is measured.

(h) Impact assessment of early tomato heel (Alternaria sorait (as)

The purpose of this test is to verify the prophylactic action of the test compounds by spraying.

Tomato seedlings (cf Outdoor Girl) are grown until the second true leaf develops. The plants are sprayed using the apparatus described in a). Test compounds are administered as a solution or suspension. For this, a 50:50 by volume mixture of acetone and water containing 0.04% Tween 20 surfactant was used.

One day after seedling treatment, the upper surface of the leaves is sprayed with a suspension of A. solani conidium spore. The suspension has a concentration of 10 ⁴ spores / ml. For 3 days after infection, the seedlings were kept in a greenhouse at almost 100% relative humidity at 21 ° C. Subsequently, the seedlings were placed in moist but not saturated with water vapor. 7 days after infection, the evaluation is made relative to control plants. Evaluate the spread and density of the heel.

(i) Impact study on wheat grain blight (Pseudocercosporella herpotrichoides; PhI)

In this assay, the compounds of the present invention are tested for in vitro activity against the fungal fungus of wheat grain.

Test compounds are dissolved or suspended in acetone and added to half-strength thawed potato dextrose agar; final agar concentration is 100 ppm test compound and 3.5% acetone. After agar hardening, the plates are infected with a 6 mm diameter agar / mycelium plug; the infectious material contains a 14-day culture of P. herpotrichoides.

The dishes are incubated at 20 ° C for 12 days and the growth radius around the infection is measured.

(j) In vitro activity against Fusarium species (Fusarium species; Fsl)

The assay evaluates the in vitro activity of the compounds of the invention against Fusarium. Fusarium causes the rot of roots and strains.

The compounds of the invention are dissolved or suspended in acetone and added to semi-potato dextrose agar medium; final concentration is 100 ppm active ingredient and 3.5% acetone. After agar hardening, the plates were infected with a mycelial agar plug of 6 mm diameter; this is a 7-day-old Fusarium sp. culture.

The dishes are incubated at 20 ° C for 5 days and the growth radius around the infection is measured.

The results of the above assays are compared to the untreated control or solvent spray control. The assessment shall be as follows:

: Less than 50% control of infection

1: 50-80%,: greater than 80% reduction in infection.

The test results are shown in Table II. Table.

HU 208 235 B ll. spreadsheet

Compound number Fungicidal activity pva pvp bcp ln Sky pr Po Dig Phi FSL 1 2 1 2A 1 1 2 2 2 1 2 2 1 2B 1 1 2 1 2 1 3 1 2 2 1 2 1 2 2 4A 2 2 2 2 2 2 4B 2 2 2 1 1 2 2 5A 1 2 1 1 2 2 5B 1 1 1 2 2 7 1 1 2 8A 1 1 2 2 2 1 2 2 2 8B 1 2 2 2 1 2 2 9A 1 2 2 2 2 2 2 9B 1 2 2 2 1 10A 1 1 2 / 2 2 2 2 2 1 10B 1 2 2 2 1 2 2 11A 1 1 2 2 2 1 2 1 11B 1 2 1 12A 2 1 2 2 1 2 12B 1 1 2 2 1 13A 1 2 2 2 2 13B 2 1 2 2 1 14A 2 1 2 2 2 14B 1 1 2 15 1 2 2 1 1 1 16A 1 2 1 1 16B 1 2 17A 1 1 2 2 2 1 2 17B 1 2 2 2 2 2 1 18A 2 2 2 2 1 1 2 1 18B 1 2 2 2 1 1 2 1 19A 1 2 2 2 2 1 19B 2 2 2 1 1 20A 2 2 2 2 1 20B 2 2 2 2 1 21A 2 2 1 1 2 21B 1 2 1 22 1 2 2 1 23 1 2 2 2 2 1 2 2 1 24A 1 1 2 2 24B 2 1 2 2 2 25 1 2 1 26A 2 2 26B 1 1 1 2 2 2 1 27 1 2 1 2 2

HU 208 235 Β

Compound number Fungicidal activity pva pvp bcp ln Sky pr Po Dig Phi FSL 28A 1 2 1 2 1 28B 2 2 2 1 29 1 1 2 30A 1 1 2 2 1 30B 1 1 2 2 1 1 2 31 1 1 2 1 32A 1 1 2 2 2 1 2 2 32B 1 2 2 2 1 1 2 2 33 2 2 1 1 1 2 2 33A 2 2 1 1 1 2 2 34 1 2 2 1 2 1 35 1 1 2 1 1 2 2

Example 37 20

Impact study on barley powder mold (vapor effect) (Erysiphe graminis; Eq)

Barley seedlings (cv. Golden Promise) are grown to single leaf (1 ⁺ ) stage in 7 cm diameter pots, and the seedlings are infected with mold spores. One day thereafter, the seedlings were sprayed with a solution containing the test compound; the solution contains water and acetone 1: 1 by volume and 0.04% by weight Tween 20. A 1 kg / ha dose of active ingredient is applied to the seedlings using a spray gun, and the sprayed seedlings are placed on a wall 30 separated by 60 cm ² between infected seedlings not treated with the test compound.

After about 7 days, the percentage of infected surface on each seedling was determined. Outside the wall, a large percentage of untreated seedlings 35 show disease. This indicates that the vapors of the compounds were not affected in these areas. In contrast, a low morbidity rate was observed for the un sprayed seedlings that were inside the wall. This justifies the effect of the vapor exiting the compounds.

Results:

(x denotes seedlings within the wall that show x% disease), "0" denotes seedlings 45 sprayed with the compound prepared in Example 13a in the upper right corner. The location of the pots holding the seedlings is shown in Figure 1. The consistently low disease state indicates that the compound of Example 13a exhibits a favorable vapor effect.

PATENT CLAIMS

Claims (3)

PATENT CLAIMS CLAIMS 1. A fungicidal composition comprising solid and liquid fillers and excipients, preferably surfactants, characterized in that the composition comprises from 0.5 to 95% by weight of the thiazole derivative of the formula (I) as an active ingredient. R is phenyl substituted with one or two halogens, I A is a carbonyl group, -C = N-OR ^1, or a group of formula (a) wherein R ¹ is C 1 -C 10 alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, (3-6) C 1-7 cycloalkyl) (C 1-3 alkyl) or phenyl (C 1-3 alkyl) optionally substituted on the phenyl moiety by one or two halogen atoms; R ¹ 'is hydrogen or C 1-6 alkyl. A process for the preparation of a thiazole derivative of formula (I): wherein: R is phenyl substituted with one or two halogens, I A is a carbonyl group, -C = N-OR ^1, or a group of formula (a) wherein R ¹ is C 1 -C 10 alkyl, C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, (3-6) C 1-6 cycloalkyl) (C 1-3 alkyl) or phenyl (C 1-3 alkyl) optionally substituted on the phenyl moiety by one or two halogen atoms; R ¹ is hydrogen or C 1 -C 6 alkyl, characterized in that a) for the preparation of compounds of formula I wherein A is a carbonyl group, wherein R is as defined above, a phosphonate derivative of formula II, wherein R is as defined above, R ⁴ , R ⁵ and R ⁶ are the same; with a different C 1-4 alkyl group - thiazolecarboxaldehyde (III) in the presence of a base I b) for the preparation of compounds of formula I wherein A is -C = N-OR ¹ - wherein R is as defined above. If desired, the compounds of formula (I) obtained by process (a) are reacted with a hydroxylamine derivative of formula (IV), wherein R ¹ is as defined above, or an acid addition salt thereof. c) if desired, the compounds of formula I obtained by process a) are prepared by reacting a compound of formula I wherein R and R ¹ are as defined above, to form compounds of formula I wherein A is a group (a). with an alkanediol of the formula wherein R ¹ 'is as defined above in the presence of a Lewis acid. 3. A method for controlling phytopathogenic fungi, wherein the composition according to claim 1 is applied to plants or their habitats infected with the fungi or exposed to the fungus, or to a composition containing 0.1-1 g of the active ingredient. kg per plant seed. HU 208 235 Β Int Cl ⁵ : A01 N 43/78