ZA200204534B - Pyrazolecarboxamide and pyrazolethioamide as fungicide. - Google Patents

Description

PR 2 - 1 -

Pyrazolecarboxamide and pyrazolethioamide as fungicide ¥ . . . » . . \ The present invention relates to novel pyrazolecarboxamides or pyrazolethioamides which have microbicidal activity, in particular fungicidal activity. The invention also relates to the ’ i preparation of these substances, to agrochemical compositions which comprise at least one of the novel compounds as active ingredient, to the preparation of the compositions mentioned and to the use of the active ingredients or compositions in agriculture and horticulture for controlling or preventing infestation of plants by phytopathogenic microorganisms, preferably fungi.

The pyrazolecarboxamides of the present invention have the general formula ue

R, N

JH (1 (1)

NJ

\

R

1 R, wherein

X is oxygen or sulfur;

R, is C,-Cjalkyl, C,-Cjhaloalkyl, C,-C,alkoxy-C,-C,alkyl or C,-C,haloalkoxy-C,-C,alky!;

R, is C,-C;haloalkyl; and

R; is halogen.

Surprisingly, it has now been found that the compounds of formula | exhibit improved biological properties which render them more suitable for the practical use in agriculture and horticulture.

Where asymmetrical carbon atoms are present in the compounds of formula |, these : compounds are in optically active form. The invention relates to the pure isomers, such as . enantiomers and diastereomers, as well as to all possible mixtures of isomers, e.g. mixtures ’ of diastereomers, racemates or mixture of racemates.

CONFIRMATION COPY fe ' -2-

Within the present specification alkyl denotes methyl, ethyl, n-propyl and isopropyl. Alkyl as part of other radicals such as alkoxyalkyl, haloalkyl or haloalkoxyalkyl is understood in an 7 analogous way. Halogen will be understood generally as meaning fluoro, chloro, bromo or

NN iodo. Fluoro, chloro or bromo are preferred meanings. Halogen as part of other radicals such ’ as haloalky! or haloalkoxyalkyl is understood in an analogous way. Typical alkoxyalkyl radicals include methoxymethyl, ethoxymethyl, propoxymethyl, methoxyethyl, ethoxyethyl and methoxypropyl. Typical haloalkoxyalkyl radicals include fluoromethoxymethyl, difluoromethoxymethyl, trifluoromethoxymethyl, 2,2,2-trifluoroethoxymethyl, 3-chloropro- poxymethyl, 2,2,3,3,3-pentafluoropropoxymethyl, 2,2 2-trifluoroethxyethyi and trifluoromethoxypropyl.

Within the group of compounds of formula | those compounds are preferred wherein

X is oxygen (subgroup A).

Another group of compounds of formula | are those wherein X is sulfur (subgroup B).

Within the subgroups A and B those compounds are preferred wherein

R, is C,-Calkyl; or

R, is C,-Cialkoxy-C,-Cjalkyl or C,-C;haloalkoxy-C,-Cialkyl;

R, is C,-C;haloalkyl; or

R, is CF;, CF,H, CFH,, CF,CI, CF,CF,, CCl;, CH,CF;, CH,CCI, or CF,CF,CF,; and

R, is fluoro, chioro or bromo (subgroups AC and BD).

Within the subgroup A are those compounds preferred wherein

R, is C,-Calkyl;

R, is C,-C;haloalkyl; and

R, is fluoro, chloro or bromo (subgroup A1).

Within the scope of subgroup At those compounds of formula | are particularly preferred, . wherein

R, is CF,, CF H, CFH,, CF,Cl, CF,CF,, CCl;, CH,CF;, CH,CCl; or CF,CF,CF; . (subgroup A2).

Ie Ta _ 3 _

Another preferred embodiment of compounds of formula | are those within subgroup A, wherein

R, is C,-C;haloalkyl,

LY

R, is C,-C;haloalkyl; and

R, is fluoro, chloro or bromo (subgroup A3).

A preferred embodiment of compounds of formula | are those within subgroup A, wherein

R, is C,-C,alkoxy-C,-Cjalkyi or C,-C;haloalkoxy-C,-C,alkyl;

R, is C,-C;haloalkyl; and

R, is fluoro, chloro or bromo (subgroup A4).

Within the scope of subgroup B those compounds of formula | are preferred, wherein

R, is C,-C;haloalkyl; and

R, is fluoro, chloro or bromo (subgroup B1).

A special group of compounds of formula | within the scope of subgroup B1 are those, wherein

R, is CF,, CF,H, CFH,, CF,Cl, CF,CF,, CCl,, CH,CF,, CH,CCl, or CF,CF,CF, (subgroup B2).

Within the scope of subgroup B another preferred embodiment of compounds of formula | are those, wherein

R, is C,-C;haloalkyl;

R, is C,-C;haloalkyl; and

R, is fluoro, chloro or bromo (subgroup B3).

A preferred embodiment of compounds of formula | are those within subgroup B, wherein : R, is C,-Cjalkoxy-C,-Cialkyl or C,-C;haloalkoxy-C,-C,alkyl;

R, is C,-C;haloalkyl; and ' R, is fluoro, chloro or bromo (subgroup B4).

Most preferred within the scope of subgroup AC are those compounds wherein

Cad LE - 4 _

Ris CH, or CH,OCH,; and

R; is CF;, CF,H or CFH, (subgroup C).

W

Particularly preferred within the scope of subgroup C are those compounds wherein ’ R, is CH,; and

R, is CF; (subgroup C1).

Another preferred embodiment within the scope of subgroup BD are those compounds wherein

R, is CH; or CH,OCH,; and

R, is CF,;, CF,H or CFH, (subgroup D).

Within the scope of subgroup D are particularly preferred those compounds wherein

R, is CH;; and

R, is CF; (subgroup D1).

The compounds according to formula | may be prepared according to the following reaction in scheme 1.

Scheme 1

R, COOH SOC, or R, CoC!

PCi5 or ao I ~ Er NU oY BEE N

N (COJCT, SN

R, R, ili (not isolated)

R O

NED A LJ

Vv HN a N

NT

R, la

R,

(s - -5-

P, S; or Lawesson-reagent R, i g v solvent: toluene, THF, dioxane N

T = O° - reflux INE

CLO

Ry Ib

R,

The pyrazole carboxylic acid Il reacts with an activating agent such thionyl chloride, phosphorous pentachloride or oxaly! chloride to give the corresponding acid chloride in the presence of a solvent at a temperature between 0°C and reflux temperature and a reaction time of 30 minutes to 24 hours. Representative solvents are toluene, benzene, xylene, hexane, cyclohexane chloroform or methylenechloride. The obtained acyl chloride lll are normally not isolated. The new carboxamides of formula {a are preferably obtained by reacting the activated carboxylic acid of formula Ill with an aromatic amine of formula IV in the presence of a solvent like toluene, benzene, xylene, hexane, cyclohexane chloroform or methylenechloride and in the presence of an acid binding agent like triethylamine, Hunig base, sodium carbonate, potassium carbonate or sodium hydrogencarbonate at a temperature between 0°C and reflux temperature. The pyrazolethioamides Ib are obtained by reacting the pyrazolecarboxamides la with phosphorpentasulfid or Lawesson-reagent in a solvent like dioxane, tetrahydrofurane or toluene at a temperature between 0°C and reflux temperature. Preferably the entire reaction sequence of scheme 1 is conducted as a single- vessel reaction.

The compounds according to the formula | may also be prepared according to the following reaction in scheme 1A.

x te -6-

Scheme 1A v HN 0]

R, ocl R,

R N

. I I ) I H

N_ —_— > No R,

N solvent, base N k, R, = halogen(Cl,Br,1) Rr. Va (1) P,Sg or I system (prepared "in situ") Lawesson reagent solvent base

S 0

R, R,

N

7 N 1 A

No R, N_ } y

R, Vb R, reagent VI "Pd-catalyst"-system 1a R solvent,base 3

S

R, 1 HR

No

CO

Ib R, reagent VI is asm,

The “in situ” prepared pyrazole carboxylic acid chloride lll reacts with an ortho- halosubstituted phenylamine in the presence of a solvent like toluene, benzene, xylene, hexane, cyclohexane, THF, chloroform or methylenechloride and in the presence of a base like sodium carbonate, sodium hydrogencarbonate, potassium carbonate, Hinig base, triethylamine or pyridine at a temperature between 0°C and reflux temperature. The obtained pyrazolecarboxamide of formula Va reacts with the p-substituted phenyl boronic acid (Vi) in the presence of a Pd-catalyst like Pd(P(phenyl);),. Pd(P(phenyl,)Cl,, PdCl, dppb, Pd,(dba),,

Pd(OAC),, PAOAC,/(o-tolyl);P, Pd(OAc),/dppf, PA(PhCN),Cl,/Ph,As, Pd(CH,CN),Cl,, ) Pd,(dba),/P(tert.butyl);, Pd(OAc),/P(tert.butyl),biphenyl, Pd(OAc),/TPPTS, Pd(OAc)./PCyj,,

Pd(OAc),/P(0-i-Pr),, Pd(OAc),/2-dimethylamino-2'-dicyclohexylphosphinobiphenyl,

Pd(OAc),/2-dimethylamino-2'-ditert.butylphosphinobiphenyl,

Pd(OAc),/(o-biphenyl)P(cyclohexyl), in a solvent like 1,2-dimethoxyethane/water, DMF, DMA,

THF iwater, dioxane/water, benzene, toluene, xylene and others and a base like sodium ! carbonate, sodium hydrogencarbonate, potassium carbonate, cesium carbonate, potassium phosphate, triethylamine, sodium hydroxide, sodium ethylate, sodium tert.butylate, silver oxide, barium carbonate, potassium fluoride or cesium fluoride at a temperature between 0°C and reflux temperature.

The pyrazolethioamide Ib is obtained by treating the pyrazolecarboxamide Va with P,S; or

Lawesson-reagent in a solvent like dioxane, tetrahydrofurane or toluene at a temperature between 0°C and reflux temperature, giving the pyrazolethioamide Vb and subsequent reaction of this pyrazolethioamide Vb with the boronic acid derivative of formula VI in the presence of a Pd-catalyst like Pd(P(phenyl)),, Pd(P(phenyl;)Cl,, PdCl, dppb, Pd,(dba),,

Pd(OAc),, PAOAC,/(o-talyl),P, Pd(OAc),/dppf, Pd(PhCN),Cl,/Ph;As, Pd(CH,CN).Cl,,

Pd,(dba)./P(tert.butyl);, Pd(OAc),/P(tert.butyl),biphenyl, Pd(OAc),/TPPTS, Pd(OAc)./PCys,

Pd(OACc),/P(O-i-Pr);, Pd(OAc),/2-dimethylamino-2’-dicyclohexylphosphinobiphenyl,

Pd(OAc),/2-dimethylamino-2’-ditert.butylphosphinobiphenyl,

Pd(OAc),/(o-biphenyl)P(cyclohexyl), in a solvent like 1,2-dimethoxyethane/water, DMF, DMA,

THF /water, dioxane/water, benzene, toluene, xylene and others and a base like sodium carbonate, sodium hydrogencarbonate, potassium carbonate, cesium carbonate, potassium phosphate, triethylamine, sodium hydroxide, sodium ethylate, sodium tert.butylate, silver oxide, barium carbonate, potassium fluoride or cesium fluoride at a temperature between 0°C and reflux temperature.

The invention relates also to the compounds of the formulae Va and Vb, wherein R,, R, and

X have the meaning as defined for formula | and R, is halogen, preferably chloro, bromo or iodo.

Compounds of formula IV are known from the literature or may be prepared following the scheme 2.

4 o -8-

Scheme 2: 1) n-BuLi 2) BOR),

R X

3 1 — = asim, 3)H + : X,=Br, | vi 1 = Bn solvent: THF — =)

NO,

NO,

X, (X, = Halogen)

Red.

H, /cat.(Pd/C,Ra-Nickel) or —_—

Fe/CH,COOH

T = RT-reflux H.N solvent: THF, alcohols, water 2 wv

The pyrazoles of formula Il are known from the literature or may be prepared following the scheme 3.

Scheme 3: idi 0 pyridine or }

OR' other base R; OR — + R,COCI or (R,O0C),0 ———"——> solvent: CHCl, or CH,Cl, R;

T = 0° C-reflux O

R'= C, -C,-alkyl or benzyl

H,N-NHR,

Oo

R,. _ COOH MOH / H,0 Re A (M = Li, Na, K) no 2

I] Shi nN,

No N

N cosolvent: e.g. alcohols ' R, " T = 0° C-reflux Ri a -9-

Surprisingly, it has now been found that the novel compounds of formula | have, for practical purposes, a very advantageous spectrum of activities for protecting plants against diseases ’ that are caused by fungi as well as by bacteria and viruses.

The compounds of formula | can be used in the agricultural sector and related fields of use as active ingredients for controlling plant pests. The novel compounds are distinguished by excellent activity at low rates of application, by being well tolerated by plants and by being environmentally safe. They have very useful curative, preventive and systemic properties and are used for protecting numerous cultivated plants. The compounds of formula | can be used to inhibit or destroy the pests that occur on plants or parts of plants (fruit, blossoms, leaves, stems, tubers, roots) of different crops of useful plants, while at the same time protecting also those parts of the plants that grow later e.g. from phytopathogenic microorganisms.

It is also possible to use compounds of formula | as dressing agents for the treatment of plant propagation material, in particular of seeds (fruit, tubers, grains) and plant cuttings (e.g. rice), for the protection against fungal infections as well as against phytopathogenic fungi occurring in the soil.

The compounds | are, for example, effective against the phytopathogenic fungi of the following classes: Fungi imperfect (e.g. Botrytis, Pyricularia, Helminthosporium, Fusarium,

Septoria, Cercospora and Alternaria) and Basidiomycetes (e.g. Rhizoctonia, Hemileia,

Puccinia). Additionally, they are also effective against the Ascomycetes classes (e.g. Venturia and Erysiphe, Podosphaera, Monilinia, Uncinula) and of the Oomycetes classes (e.g.

Phytophthora, Pythium, Piasmopara). Outstanding activity has been observed against powdery mildew (Erysiphe spp.). Furthermore, the novel compounds of formula | are effective against phytopathogenic bacteria and viruses (e.g. against Xanthomonas spp, Pseudomonas spp, Erwinia amylovora as well as against the tobacco mosaic virus). . Within the scope of present invention, target crops to be protected typically comprise the following species of plants: cereal (wheat, barley, rye, oat, rice, maize, sorghum and related : species); beet (sugar beet and fodder beet); pomes, drupes and soft fruit (apples, pears, plums, peaches, almonds, cherries, strawberries, raspberries and blackberries), leguminous plants (beans, lentils, peas, soybeans); oil plants (rape, mustard, poppy, olives, sunflowers,

5° - -10 - coconut, castor oil plants, cocoa beans, groundnuts); cucumber plants (pumpkins, cucum- bers, melons); fibre plants (cotton, flax, hemp, jute); citrus fruit (oranges, lemons, grapefruit, ) mandarins); vegetables (spinach, lettuce, asparagus, cabbages, carrots, onions, tomatoes, potatoes, paprika); lauraceae (avocado, cinnamomum, camphor) or plants such as tobacco, ' nuts, coffee, eggplants, sugar cane, tea, pepper, vines, hops, bananas and natural rubber plants, as well as ornamentals.

The compounds of formula | are used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation. To this end they are conveniently formulated in known manner to emulsifiable concentrates, coatable pastes, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations e.g. in polymeric substances. As with the type of the compositions, the methods of application, such as spraying, atomising, dusting, scattering, coating or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. The compositions may also contain further adjuvants such as stabilizers, antifoams, viscosity regulators, binders or tackifiers as well as fertilizers, micronutrient donors or other formulations for obtaining special effects.

Suitable carriers and adjuvants can be solid or liquid and are substances useful in formula- tion technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers, thickeners, binders or fertilizers. Such carriers are for example described in WO 97/33890.

The compounds of formula | are normally used in the form of compositions and can be applied to the crop area or plant to be treated, simultaneously or in succession with further compounds. These further compounds can be e.g. fertilizers or micronutrient donors or other preparations which influence the growth of plants. They can also be selective herbicides as well as insecticides, fungicides, bactericides, nematicides, molluscicides or mixtures of several of these preparations, if desired together with further carriers, surfactants or application promoting adjuvants customarily employed in the art of formulation.

The compounds of formula | can be mixed with other fungicides, resulting in some cases in unexpected synergistic activities.

a - -11 -

Mixing components which are particularly preferred are azoles such as azaconazole, bitertanol, propiconazole, difenoconazole, diniconazole, cyproconazole, epoxiconazole, ) fluquinconazole, flusilazole, flutriafol, hexaconazole, imazalil, imibenconazole, ipconazole, tebuconazole, tetraconazole, fenbuconazole, metconazole, myclobutanil, perfurazoate, penconazole, bromuconazole, pyrifenox, prochloraz, triadimefon, triadimenol, triflumizole or triticonazole; pyrimidiny! carbinoles such as ancymidol, fenarimol or nuarimotl; 2-amino- pyrimidine such as bupirimate, dimethirimol or ethirimol; morpholines such as dodemorph, fenpropidin, fenpropimorph, spiroxamin or tridemorph; anilinopyrimidines such as cyprodinil, pyrimethanil or mepanipyrim; pyrroles such as fenpiclonil or fludioxonil; phenylamides such as benalaxyl, furalaxyl, metalaxyl, R-metalaxyl, ofurace or oxadixy!l; benzimidazoles such as benomyl, carbendazim, debacarb, fuberidazole or thiabendazole; dicarboximides such as chlozolinate, dichlozoline, iprodine, myclozoline, procymidone or vinclozolin; carboxamides such as carboxin, fenfuram, flutolanil, mepronil, oxycarboxin or thifluzamide; guanidines such as guazatine, dodine or iminoctadine; strobilurines such as azoxystrobin, kresoxim-methyl, metominostrobin, SSF-129, methyl 2-[(2-trifluoromethyl)-pyrid-6-yloxymethyl]-3- methoxyacrylate or 2-[a{[(a-methy!-3-trifluoromethyl-benzyl)imino}-oxy}-o-tolyl}-glyoxylic acid- methylester-O-methyloxime (trifloxystrobin); dithiocarbamates such as ferbam, mancozeb, maneb, metiram, propineb, thiram, zineb or ziram; N-halomethylthio-dicarboximides such as captafol, captan, dichlofluanid, fluoromide, folpet or tolyfluanid; copper compounds such as

Bordeaux mixture, copper hydroxide, copper oxychloride, copper sulfate, cuprous oxide, mancopper or oxine-copper; nitrophenol derivatives such as dinocap or nitrothal-isopropyl; organo phosphorous derivatives such as edifenphos, iprobenphos, isoprothiolane, phosdiphen, pyrazophos or toclofos-methyl; and other compounds of diverse structures such as acibenzolar-S-methyl, anilazine, blasticidin-S, chinomethionat, chloroneb, chlorothalonil, cymoxanil, dichlone, diclomezine, dicloran, diethofencarb, dimethomorph, dithianon, etridiazole, famoxadone, fenamidone, fentin, ferimzone, fluazinam, flusulfamide, fenhexamid, fosetyl-aluminium, hymexazol, kasugamycin, methasulfocarb, pencycuron, phthalide, polyoxins, probenazole, propamocarb, pyroquilon, quinoxyfen, quintozene, sulfur, triazoxide, tricyclazole, triforine, validamycin, (S)-5-methyl-2-methylthio-5-phenyl-3-phenyl-amino-3,5- dihydroimidazol-4-one (RPA 407213), 3,5-dichloro-N-(3-chloro-1-ethyl-1-methyl-2- oxopropyl)-4-methylbenzamide (RH 7281), N-allyl-4,5-dimethyl-2-trimethylsilylthiophene-3- carboxamide (MON 65500), 4-chloro-4-cyano-N,N-dimethyl-5-p-tolylimidazole-1-sulfon-

Claims (10)

vor -20- What is claimed is

1. A pyrazolecarboxamide of formula es R, N 1H malo N \ R 1 R, wherein X is oxygen or sulfur; R, is C,-C,alkyl, C,-C;haloalkyl, C,-C,alkoxy-C,-C,alkyl or C,-C;haloalkoxy-C,-Csalkyl; R, is C,-C;haloalkyl; and R, is halogen.

2. A compound of formula | according to claim 1, wherein X is oxygen.

3. A compound of formula | according to claim 1, wherein Xis sulfur.

4. A compound of formula | according to claims 2 or 3, wherein R, is C,-C,alkyl, and R, is fluoro, chloro or bromo.

5. A compound of formula | according to claim 4, wherein R, is CF,, CF,H, CFH,, CF.CF,, CCl,, CH,CF, CH,CCl, or CF,CF,CF,.

‘

6. A compound of formula | according to claims 2 or 3, wherein R, is C;-C;haloalkyl; and R, is fluoro, chloro or bromo.

LE - 21 -

7. A process for the preparation of compounds of formula | which comprises reacting the starting materials according a) to the scheme R, COOH SOCI, or R, cocl ) PClg or TT] ] ~ ——— N N (CO),CT, ~N i R, n R, mn ~~) i R, Iv N HN A | H - " R, la C R, S P, Sg or Lawesson-reagent R 4g solvent: toluene, THF, dioxane 2 N T = O° - reflux Ry | H — ee ——— ~N LQ ! Ib R, wherein X, R,, R, and R, are as defined for formula | in claim 1; or b) according to the scheme 0 R, ocl HN R, N R | H No I N_ R, N N solvent, base R, R, Va ll oo» -22. 0 Pd-catalyst-system R , solvent, base 2 N H - on la; or "(Bom Ri _ Vi R, c) according to the sheme 0 R, ocCl HNN R, N I R lJ H Nan I Nan R, solvent, base R, R, Va Hl S P,S; or Lawesson-reagent R ie 2 N Vb - a ‘ni oy R, R, S Pd-catalyst-system R solvent, base 2 N boo H _—— oy ) ib R R—(_)—oom, Vi R, wherein R,, R, and R; are as defined for formula | in claim 1 and R, is chloro, bromo or iodo. . 8. A composition for controlling microorganisms and preventing attack and infestation of plants therewith, wherein the active ingredient is a compound as claimed in claim 1 together with a suitable carrier.

FORE - 23 —-

9. A method of controlling or preventing infestation of cultivated plants by phytopathogenic microorganisms by application of a compound of formula | as claimed in claim 1 to plants, to ; parts thereof or the locus thereof. '

10. A compound of formula V X R, N H Nan R, R, wherein X is oxygen or sulfur, R,is C,-Cjalkyl, C,-C;haloalkyl, C,-Cjalkoxy-C,-C,alkyl or C,-C;haloalkoxy-C,-Csalkyl; R, is C,-C;haloalkyl; and R, is chloro, bromo or iodo.