2-Mercapto-5-Pyrazinyl-1,3,4-Oxadiazoles or 2-Mercapto-5-Pyrazinyl-1,3,4-Thiadiazoles as Nematicides

The present invention relates to novel substituted 2-mercapto-5-pyrazinyl-1,3,4-oxadiazoles and 2-mercapto-5-pyrazinyl-1,3,4-thiadiazoles, to their preparation and to nematicidal compositions which contain at least one of these compounds as active ingredient. The invention further relates to novel intermediates for the synthesis of the compounds of the invention and to the use of 2-mercapto-5-pyrazinyl-1,3,4-oxadiazoles and 2-mercapto-5-pyrazinyl-1,3,4-thiadiazoles and compositions containing them for controlling nematicides, especially plant-destructive nematicides.

The 2-mercapto-5-pyrazinyl-1,3,4-oxadiazoles and 2-mercapto-5-pyrazinyl-1,3,4-thiadiazoles of this invention, and salts thereof, have the general formula I ##STR2## wherein

X is oxygen or sulfur,

R' is C.sub.1 -C.sub.5 alkyl, unsubstituted or substituted by halogen, C.sub.1 -C.sub.3 alkoxy or cyano; unsubstituted or halogen-substituted C.sub.3 -C.sub.7 alkenyl; unsubstituted or halogen-substituted C.sub.3 -C.sub.7 alkynyl,

R is C.sub.1 -C.sub.3 alkyl, unsubstituted C.sub.1 -C.sub.3 alkoxy or C.sub.1 -C.sub.3 alkoxy which is substituted by halogen or C.sub.1 -C.sub.3 alkoxy; halogen, cyano, hydroxy, amino or amino which is substituted by one or two C.sub.1 -C.sub.3 alkyl groups; or is aminocarbonyl; and

n is 0, 1, 2 or 3.

Alkyl by itself or as moiety of another substituent such as alkoxy will be understood as meaning straight chain and branched alkyl groups. Such groups include methyl, ethyl as well as n- and i-propyl, -butyl and -pentyl groups. Halogen-substituted alkyl is a mono- to perhalogenated alkyl group, e.g. CHCl.sub.2, CH.sub.2 F, CCl.sub.3, CH.sub.2 Cl; CHFCH.sub.3, CH.sub.2 CH.sub.2 Br, CF.sub.2 CF.sub.3, C.sub.2 Cl.sub.5, CH.sub.2 Br, CHBrCl and the like, and is preferably CHF.sub.2. Alkenyl is typically 1-propenyl, allyl, 1-butenyl, 2-butenyl or 3-butenyl, as well as chains containing several double bonds. Alkynyl is typically 2-propynyl, 1-butynyl, 2-butynyl, 4-pentynyl and the like. Halogen is fluorine, chlorine, bromine or iodine, and is preferably fluorine, chlorine or bromine.

Examples of salt-forming inorganic acids are hydrohalic acids such as hydrofluoric acid, hydrochloric acid, hydrobromic acid or hydriodic acid, as well as sulfuric acid, phosphoric acid, phosphorous acid and nitric acid; examples of salt-forming organic acids are acetic acid, trifluoroacetic acid, trichloroacetic acid, propionic acid glycolic acid, thiocyanic acid, lactic acid, succinic acid, citric acid, benzic acid, cinnamic acid, oxalic acid, formic acid, benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, salicyclic acid, p-aminosalicyclic acid, 2-phenoxybenzoic acid and 2-acetoxybenzoic acid.

Oxadiazole and thiadiazole derivatives disclosed as having nematicidal properties are known. Thus U.S. patent specification 3,770,754 discloses such compounds with hetero atoms in 1,2,4-position, whereas U.S. Pat. No. 4,454,147 describes 1,3,4-thiadiazole derivatives in which, as compared with the compounds of this invention, the heterocycle is substituted by a chlorine atom instead of by mercapto groups. As nematicides these known compounds have so far been unable to meet fully the demands made of them in practice. Further, oxadiazole derivatives having fungicidal properties are disclosed in German Offenlegungsschrift 2 361 613. However, this reference does not expressly mention any of these compounds that fall within the scope of formula I of the present invention.

With the compounds of formula I of the present invention it is now possible to make a valuable contribution to controlling plant nematodes which cause considerable agricultural damage to plants. By controlling such nematodes, harvest losses of cultivated plants such as potatoes, cereals, carrots, rape, cabbage and vegetable and also damage caused in nurseries and to ornamentals can be inhibited in the long term. The compounds of the present invention are distinguished in particular by the feature that they effectively control soil nematodes which parasites on roots, e.g. those nematodes of the genera Heterodera and Globodera (cystogenic nematodes), Meloidogyne (root-knot nematodes) and also of the general Radopholus, Pratylenchus, Longidorus, Trichodorus and Xiphinema. The nematode genera Ditylenchus (stem parasites), Aphelenchoides (bud and leaf nematodes) and Anguina (seed-gall nematodes) can also be effectively controlled with the compounds of this invention.

Preferably the compounds of formula I are used for effectively controlling particularly harmful nematode species of the genus Meloidogyne, e.g. Meloidogyne incognita, of the genus Heterodera, e.g. Heterodera glycines (soybean cyst nematode), of the genus Globodera, e.g. Globodera rostochienis (potato cyst nematode), as well as representatives of migrating endoparasites such as Pratylenchus penetrans or Radopholus similis, and representative of ectoparasites such as Trichodorus spp. and Xiphinema spp.

To control plant nematodes and for the preservation of plant health, the novel compounds may be used curatively, preventively or systemically. They have a wide activity spectrum against the various nematode species and therefore meet the requirement made of them in practice. The nematicidal mode of action of the compounds of the present invention is advantageously coupled with their low phytotoxicity, whereby the generally desirable lessening of risk to the environment is especially taken into account.

Within the scope of the present invention, preferred 2-mercapto-5-pyrazinyl-1,3,4-oxadiazoles are those of formula Ia ##STR3## wherein R' is difluoromethyl, cyanomethyl, difluoromethyldifluoromethyl or propargyl, R.sub.1 and R.sub.3 are hydrogen and R.sub.2 is hydrogen or chlorine.

Also preferred are those 2-mercapto-5-pyrazinyl-1,3,4-thiadiazoles of formula Ib ##STR4## wherein R' is difluoromethyl, tetrafluoroethyl, cyanomethyl, allyl, propargyl or 2-bromoalkyl, R.sub.1 and R.sub.2 are each independently of the other hydrogen, chlorine, bromine or methoxy, and R.sub.3 is hydrogen or methylamino.

Among this group of compounds, preferred individual compounds are 2-difluoromethylthio-5-pyrazinyl-1,3,4-thiadiazole and 2-difluoromethylthio-5-pyrazinyl-1,3,4-oxadiazole.

The compounds of formula I are prepared by

(a) condensing a compound of formula II ##STR5## or a compound of formula III ##STR6## with a compound of formula IV

in an inert solvent or mixture of solvents at room temperature or at elevated temperature, in the absence or presence of a catalyst and under normal or elevated pressure, the reaction being carried out in the presence of a base if the starting material is a compound of formula II; or

(b) reacting a compound of formula II ##STR7## with a compound of formula V ##STR8## in an inert solvent or mixture of solvents at elevated temperature and in the absence or presence of a catalyst and under normal or elevated pressure, by means of an addition reaction to give a compound of formula Ic ##STR9## or a compound of formula Id ##STR10## in which formulae II, III, IV, V, Ic and Id above Me is an alkali metal or ammonium, Hal is halogen, preferably chlorine, bromine or iodine, and R" is fluorine or trifluoromethyl, and R, R' and n are as defined for formula I.

Examples of solvents or diluents suitable for the preparation of the compounds of this invention are ethers and etheral compounds such as dialkyl ethers (diethyl ether, diisopropyl ether, tert-butylmethyl ether and the like), anisole, dioxane, tetrahyrofuran; aliphatic and aromatic hydrocarbons such as benzene, toluene, petroleum ether; halogenated hydrocarbons such as chlorobenzene, mehylene chloride, chloroform, ethylene chloride, carbon tetrachloirde, tetrachloroethylene; nitriles such as acetonitrile, propionitrile; N,N-dialkylated amides such as dimethylformamide; dimethyl sulfoxide; ketones such as acetone, diethyl ketone, methyl ethyl ketone; and also water and alcohols such as methanol, ethanol, isopropanol or butanol; and, quite generally, mixtures of such solvents with one another.

Suitable bases are both organic and inorganic bases; e.g. preferably tertiary amines such as trialkylamines (trimethylamine, triethylamine, tripropylamine and others), as well as oxides, hydroxides, carbonates and bicarbonates of alkali metals and alkaline earth metals (e.g. CaO, BaO, NaOH, KOH, Ca(OH).sub.2, KHCO.sub.3, NaHCO.sub.3, Ca(HCO.sub.3).sub.2, K.sub.2 CO.sub.3, Na.sub.2 CO.sub.3 etc.), and also acetates such as CH.sub.3 COONa or CH.sub.3 COOK. Further suitable base are alkali metal alcoholates such as sodium methylate, sodium propylate, potassium tert-butylate or sodium ethylate.

The addition of catalytic amounts of a crown ether, e.g. 18-crown-6 or 15-crown-5 promotes the reaction course of the preparatory processes. The catalytic addition of tetraalkylamine salts, e.g. tetraalkylamino chlorides or bromides, preferably tetra-n-butylamino bromide, is also useful for the same purpose. In addition, alkali metal iodides, preferably potassium iodide, may be used with advantage as catalysts.

The reaction temperature in the preparatory processes are in the range from 10.degree. to 90.degree. C., preferably from 30.degree. to 80.degree. C. The reaction has to be carried out under atmospheric or under elevated pressure.

Some of the starting compounds of formula II are known and some are novel. Novel compounds are those 2-mercapto-5-pyrid-2-yl-1,3,4-oxadiazole of formula IIa' ##STR11## and those 2-mercapto-5-pyrid-2-yl-1,3,4-thiadiazoles of formula IIb' ##STR12## wherein R.sub.1, R.sub.2 and R.sub.3 are each independently ethyl, propyl or isopropyl, unsubstituted C.sub.1 -C.sub.3 alkoxy or C.sub.1 -C.sub.3 alkoxy which is substituted by halogen or C.sub.1 -C.sub.3 alkoxy, unsubstituted or halogen-substituted C.sub.3 -C.sub.7 alkenyl; or are C.sub.3 -C.sub.7 alkynyl, C.sub.1 -C.sub.3 alkylthio, halogen, cyano, hydroxy, amino or amino which is substituted by one or two C.sub.1 -C.sub.3 alkyl groups; or are aminocarbonyl.

The novel compounds of formulae IIa' and IIb' (q.v. Table 0) are intermediates for the preparation of useful nematicides and thus constitute an object of the present invention.

The starting compounds of formula II can be prepared by known methods (q.v. J. Pharm. Sci. 1972, 61(9), 1483-6, Ca 77, 126568 g, 1972) or by methods analogous thereto.

The invention also relates to compositions for controlling plant-destructive nematodes and also for protecting plants from attack by nematodes, which compositions containing compounds of formula I.

The present invention also relates to the preparation of nematicidal compositions, which comprises homogeneously mixing compounds of formula I with one or more of the carriers and adjuvants described herein. The invention further relates to a method of treating plants, which comprises applying the compounds of formula I or the novel compositions thereto.

A preferred method of applying a compound of formula I or a nematicidal composition containing at least one compound of formula I is soil application, which comprises treating the locus of the plants with a liquid or solid formulation.

The compounds of formula I may also be applied to seeds (dressing/coating) either by impregnating the seeds in a liquid formulation of the active ingredient or by coating them with a solid formulation. Moreover, in special cases, further types of application are also possible, e.g. selective treatment of the plant stems, buds or leaves.

The compounds of formula I are normally applied 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 also include other substances applied on agriculture which are used to increase production by promoting the growth of useful plants. Examples of such substances are fertilisers, herbicides, insecticides, fungicides, mollusicides and the like, or mixtures of several of these substances, if desired, together and further carriers, surfactants or other application promoting adjuvants customarily employed in the art of formulation.

Suitable carriers and adjuvants can be solid or liquid and correspond to the substances ordinarily employed in formulation technology, e.g. natural or regenerated mineral substances, solvents, dispersants, wetting agents, tackifiers thickeners binders or fertilisers.

The compounds of formula I are used in unmodified form or, preferably, together with the adjuvants conventionally employed in the art of formulation, and are therefore formulated in known manner to emulsifiable concentrates, directly sprayable or dilutable solutions, dilute emulsions, wettable powders, soluble powders, dusts, granulates, and also encapsulations in e.g. polymer substances. As with the nature of the compositions, the methods of application, such as spraying, dusting, scattering or pouring, are chosen in accordance with the intended objectives and the prevailing circumstances. Advantageous rates of application are normally from 500 g to 6 kg of active ingredient (a.i.) per hectare, preferably from 1 to 4 kg a.i./ha.

The formulations, i.e. the compositions containing the compound (active ingredient) of formula I and, where appropriate, a solid or liquid adjuvant, are prepared in known manner, e.g. by homogeneously mixing and/or grinding the active ingredients with extenders, e.g. solvents solid carriers and, where appropriate, surface-active compounds (surfactants).

Suitable solvents are: aromatic hydrocarbon, preferably the fractions containing 8 to 12 carbon atoms, e.g. xylene mixtures or substituted naphthalenes, phthalate such as dibutyl phthalate or dioctyl phthalate, aliphatic hydrocarbons such as cyclohexane or paraffins, alcohols and glycols and their ethers and esters, such as ethanol, ethylene glycol, ethylene glycol monomethyl or monoethyl ether, ketones such as cyclohexanone, strongly polar solvents such as N-methyl-2-pyrrolidone, dimethyl sulfoxide or dimethylformamide, as well as vegetable oils or epoxidised vegetable oils such as epoxidised coconutoil, sunflower oil or soybean oil; or water.

The solid carriers used e.g. for dusts and dispersible powders, are normally natural mineral fillers such as calcite, talcum, kaolin, montmorillonite or attapulgite. In order to improve the physical properties it is also possible to add highly dispersed silicic acid or highly dispersed absorbent polymers. Suitable granulated adsorptive carriers are porous types, for example pumice, broken brick, sepiolite or bentonite; and suitable nonsorbent carriers are materials such as calcite or sand. In addition, a great number of pregranulated materials of inorganic or organic nature can be used, e.g. especially dolomite or pulverised plant residues.

Depending on the nature of the compound of formula I to be formulated, suitable surface-active compounds are non-ionic, cationic and/or anionic surfactants having good emulsifying, dispersing and wetting properties. The term "surfactants" will also be understood as comprising mixtures of surfactants.

Suitable anionic surfactants can be both water-soluble soaps and water-soluble synthetic surface-active compounds.

Suitable soaps are the alkali metal salts, alkaline earth metal salts or unsubstituted or substituted ammonium salts or higher fatty acids (C.sub.10 -C.sub.22), e.g. the sodium or potassium salts of oleic or stearic acid, or of natural fatty acid mixtures which can be obtained e.g. from coconut oil or tallow oil. Mention may also be made of fatty acid methyltaurin salts.

More frequently, however, so-called synthetic surfactants are used, especially fatty sulfonates, fatty sulfates, sulfonated benzimidazole derivatives or alkylsulfonates.

The fatty sulfonates or sulfates are usually in the form of alkali metal salts, alkaline earth metal salts or unsubstituted or substituted ammonium salts and contain a C.sub.8 -C.sub.22 alkyl radical which also includes the alkyl moiety of acyl radicals, e.g. the sodium or calcium salt of lignosulfonic acid, of dodecylsulfate or of a mixture of fatty alcohol sulfates obtained from natural fatty acids. These compounds also comprise the salts of sulfuric acid esters and sulfonic acids of fatty alcohol/ethylene oxide adducts. The sulfonated benzimidazole derivatives preferably contain 2 sulfonic acid groups and one fatty acid radical containing 8 to 22 carbon atoms. Examples of alkylarylsulfonates are the sodium, calcium or triethanolamine salts of dodecylbenzenesulfonic acid, dibutylnaphthalensulfonic acid, or of a naphthenesulfonic acid/formaldehyde condensation product. Also suitable are corresponding phosphates, e.g. salts of the phosphoric acid ester of an adduct of p-nonylphenol with 4 to 14 moles of ethylene oxide.

Non-ionic surfactants are preferably polyglycol ether derivatives of aliphatic or cycloaliphatic alcohols, or saturated or unsaturated fatty acids and alkylphenols, said derivatives containing 3 to 30 glycol ether groups and 8 to 20 carbon atoms in the (aliphatic) hydrocarbon moiety and 6 to 18 carbon atoms in the alkyl moiety of the akylphenols.

Further suitable non-ionic surfactants are the water-soluble adducts of polyethylene oxide with polypropylene glycol, ethylenediamino-propylene glycol and alkylpolypropylene glycol containing 1 to 10 carbon atoms in the alkyl chain, which adducts contain 20 to 250 ethylene glycol ether groups and 10 to 100 propylene glycol ether groups. These compounds usually contain 1 to 5 ethylene glycol units per propylene glycol unit.

Representative examples of non-ionic surfactants are nonylphenolpolyethoxyethanols, castor oil polyglycol ethers, polypropylene/polyethylene oxide adducts, tributylphenoxypolyethyleneethanol, polyethylene glycol and octylphenoxypolyethoxyethanol. Fatty acid esters of polyoxyethylene sorbitan, e.g. polyoxyethylene sorbitan trioleate, are also suitable non-ionic surfactants.

Cationic surfactants are preferably quaternary ammonium salts which contain, as N-substituent, at least one C.sub.8 -C.sub.22 alkyl radical and, as further substituents, unsubstituted or halogenated alkyl, benzyl or hydroxy-lower alkyl radicals. The salts are preferably in the form of halides, methylsulfates or ethylsulfates, e.g. stearyltrimethylammonium chloride or benzyldi(2-chloroethyl)ethylammonium bromide.

The surfactants customarily employed in the art of formulation are described e.g. in "McCutcheon's Detergents and Emulsifiers Annual", MC Publishing Corp., Ridgewood, N.J., 1979; Dr. Helmut Stache, "Tensid Taschenbuch" (Handbook of Surfactants), Carl Hanser Verlag, Munich/Vienna, 1981.

The agrochemical compositions usually contain 0.1 to 99% by weight, preferably 0.1 to 95% by weight, of a compound of formula I, 99.9 to 1% by weight, preferably 99.8 to 5% by weight, of a solid or liquid adjuvant, and 0 to 25% by weight, preferably 0.1 to 25% by weight, of a surfactant.

Whereas commercial products will preferably be formulated as concentrates, the end user will normally employ dilute formulations.

The compositions may also contain further auxiliaries such as stabilisers, antifoams, viscosity regulators, binders, tackifiers as well as fertilisers or other active ingredients for obtaining special effects.

Such agrochemical compositions constitute an object of the present invention.

The invention is illustrated in more detail by the following nonlimitative Examples.

To 210 ml of concentrated sulfuric acid are added, in portions, 50 g (0.20 mol) of the compound ##STR14## at -5.degree. to 0.degree. C. The reaction mixture is then stirred for 90 minutes at 0.degree. C. and poured on to 1000 g of ice. The precipitate is filtered with suction and the solid is dissolved in 800 ml of 1sodium hydroxide. The solution is clarified with activated carbon and filtered. The clear solution is strongly acidified with 1N hydrochloric acid, and the precipitated product is isolated by filtration, washed with water and vacuum dried, affording 30.6 g (78.7% of theory) of 2-mercapto-5-pyrazinyl-1,3,4-thiadiazole of m.p. 224.degree.-228.degree. C.

To a solution of 6.2 g of 85% potassium hydroxide in 18 ml of water is added a solution of 6 g (0.03 mol) of 2-mercapto-5-pyrazin-2-yl-1,3,4-thiadiazole in 90 ml of dioxane. Then 0.2 g of potassium iodide and 0.2 g of tetrabutylammonium bromide are added to the reaction mixture and 13 g of gaseous difluoromethane are introduced over 6 hours at 22.degree. to 37.degree. C. After evaporating off the dioxane, the reaction mixture is diluted with ethyl acetate, the aqueous phase is separated and the organic solution is washed cold with 1N sodium hydroxide solution and water, dried over sodium sulfate and clarified with activated carbon. The ethyl acetate is removed under vacuum and the residue is crystallised from ethyl acetate/hexane, affording 312 g (43%) of the title compound with a melting point of 113.degree.-115.degree. C.

The following compounds of this invention can be prepared in accordance with the foregoing Preparatory Examples and with the processes described above. These compounds serve to illustrate the invention and imply no limitation thereof.

Emulsions of any required concentration can be produced from such concentrates by dilution with water.

These solutions are suitable for application in the form of microdrops.

The active ingredient is dissolved in methylene chloride, the solution is sprayed onto the carrier, and the solvent is subsequently evaporated off in vacuo.

Ready-for-use dusts are obtained by intimately mixing the carriers with the active ingredient.

(throughout, percentages are by weight)

The active ingredient is thoroughly mixed with the adjuvants and the mixture is thoroughly ground in a suitable mill, affording wettable powders which can be diluted with water to give suspensions of the desired concentration.

Emulsions of any required concentration can be obtained from this concentrate by dilution with water.

Ready-for-use dusts are obtained by mixing the active ingredient with the carrier, and grinding the mixture in a suitable mill.

The active ingredient is mixed and ground with the adjuvants, and the mixture is subsequently moistened with water. The mixture is extruded and then dried in a stream of air.

The finely ground active ingredient is uniformly applied, in a mixer, to the kaolin moistened with polyethylene glycol. Non-dusty coated granulates are obtained in this manner.

The finely ground active ingredient is intimately mixed with the adjuvants, giving a suspension concentrate from which suspensions of any desired concentration can be obtained by dilution with water.

Eggs of Meloidogyne incognita are mixed into sand. This mixture is then put into 200 ml earthenware pots (5000 eggs per pot). On the same day a three-week-old tomato plant is planted in each pot and the formulated test compound is introduced into the pots by drench application (0.006% of active ingredient, based on the volume of the soil). The potted plants are stood in a greenhouse at a temperature of 26.+-.1.degree. C. and a relative humidity of 60%. After 4 weeks evaluation is made by examining the plants for root-knot formation in accordance with the Knot Index.

Compounds of Table 1 exhibit good activity against Meloidogyne incognita in that they substantially reduce root-knot formation. On the other hand, untreated and infected control plants exhibit severe root-knot formation (=100%). Thus, in this test, e.g. compounds 1.1, 1.2, 1.9, 1.10, 1.20 and 1.21 inhibit root-knot formation almost completely (0-10% attack).