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WO1997038995A1 - Fungicidal oxazolidinedione derivatives - Google Patents

Fungicidal oxazolidinedione derivatives Download PDF

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Publication number
WO1997038995A1
WO1997038995A1 PCT/GB1997/000822 GB9700822W WO9738995A1 WO 1997038995 A1 WO1997038995 A1 WO 1997038995A1 GB 9700822 W GB9700822 W GB 9700822W WO 9738995 A1 WO9738995 A1 WO 9738995A1
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WIPO (PCT)
Prior art keywords
alkyl
halo
alkoxy
optionally substituted
aryl
Prior art date
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PCT/GB1997/000822
Other languages
French (fr)
Inventor
Margaret Jean Huggett
William Guy Whittingham
Kirsteen Isobel Buchanan
Original Assignee
Zeneca Limited
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Filing date
Publication date
Application filed by Zeneca Limited filed Critical Zeneca Limited
Priority to AU21673/97A priority Critical patent/AU2167397A/en
Publication of WO1997038995A1 publication Critical patent/WO1997038995A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/74—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3
    • A01N43/76—1,3-Oxazoles; Hydrogenated 1,3-oxazoles

Definitions

  • the present invention relates to novel oxazolidinedione derivatives, to processes for preparing them, to fungicidal compositions containing them and to methods of using them to combat fungi, especially fungal infections of plants.
  • R 1 is a C-linked 6-membered heteroaromatic ring containing 2 or 3 nitrogen atoms and which is optionally N- or C-substituted with one or more of halo, hydroxy, oxo, C ⁇ -6 alkyl, C 3 . 6 cycloalkyl, halo(C ⁇ . 6 )alkyl, C ⁇ -4 alkoxy(C ⁇ . 6 )alkyl, aryl(C ⁇ -6 )alkyl, Ci. 6 alkoxy, halo(C ⁇ . 6 )alkoxy, C 2 . 4 alkenyloxy, d_ 6 alkylthio, C ⁇ -6 alkylcarbonyl, C ⁇ .
  • 6 alkylcarbonylamino Ci.6 alkoxycarbonyl, arylcarbonyl, aryl, aryloxy, or heteroaryl, the aryl and heteroaryl substituents themselves being optionally substituted with one or more of halo, C ⁇ . 6 alkyl, halo(C ⁇ . 6 )alkyl, C
  • R 2 is phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, thiadiazolyl, oxadiazolyl or tetrazolyl, any of which is optionally substituted with one or more of halo, C ⁇ -6 alkyl, halo(C[. 6 )alkyl, C
  • alkyl moieties including the alkyl moieties of haloalkyl, alkoxy, alkylthio, alkylsulphonyl, etc., suitably contain from 1 to 6 , for example from 1 to 4, carbon atoms in the form of straight or branched chains. Examples are methyl, ethyl, n- and wo-propyl, n-, sec-, iso- and tert-butyl and n-hexyl.
  • C 3 . 6 cycloalkyl includes cyclopropyl and cyclohexyl.
  • Halo includes fluoro, chloro, bromo and iodo. Most commonly it is fluoro or chloro.
  • Haloalkyl is typically trifluoromethyl and haloalkoxy is typically trifluoromethoxy.
  • Aryl is usually phenyl but also includes naphthyl.
  • Heteroaryl includes the residues of 6-membered heteroaromatic rings containing from 1 to 3 N atoms, eg pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or 1,3,5-triazinyl, and the residues of 5-membered heteroaromatic rings containing 1 to 3 heteroatoms selected from N, O and S, eg furyl, thienyl, pyrrolyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, pyrazolyl, imidazolyl, thiadiazolyl, oxadiazolyl or triazolyl.
  • heteroaryl is pyridyl, thienyl, furyl, pyrrolyl, isoxazolyl or isothiazolyl.
  • the 6-membered heteroaromatic ring R 1 is selected from pyrimidinyl, pyrazinyl, pyridazinyl and 1,2,4- and 1,3,5-triazinyl.
  • R 1 is 2-pyrimidinyl, 4-pyrimidinyl, 5- pyrimidinyl, 2-pyrazinyl, 3 -pyridazinyl, or 2-( 1,3,5-triazinyl) optionally N- or C-substituted with one or more of the R 1 substituents listed above.
  • R 1 is 2-pyrimidinyl optionally substituted with hydroxy, oxo, CM alkyl, C 3 . 6 cycloalkyl, halo(C
  • the aryl or heteroaryl substituent of the 6-membered heteroaromatic ring R 1 may be any aryl or heteroaryl group defined above and may be optionally substituted with one or more of halo, CM alkyl, halo(C ⁇ . 4 )alkyl, C M alkoxy, halo(C ⁇ . 4 )alkoxy, C M alkoxy (C ⁇ . 4 )alkyl, nitro, amino, mono- or di(C M )alkylamino, cyano, C M alkoxycarbonyl or C
  • the group R 2 is typically unsubstituted phenyl but may also be phenyl substituted with a bromine or iodine atom, with 1 to 5 chlorine or fluorine atoms, with 4 chlorine or fluorine atoms and a methyl or trifluoromethyl group or with 1 to 3 substituents selected from halo, CM alkyl, halo(C ⁇ . 4 )alkyl, C M alkoxy, halo(C ⁇ . 4 )alkoxy, C I-4 alkylthio, nitro, cyano, thiocyanato, C M alkylsulphonyl, halo(C ⁇ .
  • R 2 is, for example, 2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 3-pyridazinyl, 3-thienyl, 3- or 5-pyrazolyl, 2-thiazolyl, 3-(l,2,4-triazolyl), 5- (1,2,3-thiadiazolyl) or 5-tetrazolyl, any of which is optionally substituted with 1 to 3 substituents selected from halo, C
  • R 2 is, for example, 2-, 3- or 4-quinolinyl, 4-quinazolinyl, 1- phthalazinyl, 2-quinoxalinyl, 3-(l,2,4-benzotriazinyl), 2-benzoxazolyl or 2-benzothiazolyl, any of which is optionally substituted in its fused benzene ring with halo, C M alkyl, C M alkoxy or nitro and in its heterocyclic ring with halo, C M alkyl, halo(C
  • the present invention is illustrated by the compounds of general formula (I) listed in
  • Table 1 comprises 167 compounds of the general formula (I), wherein R' is 4-methyl- 6-hydroxypyrimidin-2-yl and R 2 has the value listed below.
  • Table 2 comprises 167 compounds of the general formula (I), wherein R 1 is 4- methoxy-6-methylpyrimidin-2-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 3 comprises 167 compounds of the general formula (I), wherein R' is 4- allyloxy-6-methylpyrimidin-2-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 4 comprises 167 compounds of the general formula (I), wherein R 1 is 4,6- dimethoxypyrimidin-2-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 5 comprises 167 compounds of the general formula (I), wherein R 1 is 4,6- dimethylpyrimidin-2-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 6 comprises 167 compounds of the general formula (I), wherein R 1 is 1,4- dimethyl-6-oxopyrimidin-2-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 7 comprises 167 compounds of the general formula (I), wherein R' is 2- wopropyl-6-hydroxypyrimidin-4-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 8 comprises 167 compounds of the general formula (I), wherein R 1 is 2-(5- trifluoromethylpyrid-2-yl)-6-methylpyrimidin-4-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 9 comprises 167 compounds of the general formula (I), wherein R 1 is pyrimidin- 5-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 10 comprises 167 compounds ofthe general formula (I), wherein R 1 is 2- methylpyrimidin-5-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 11 comprises 167 compounds of the general formula (I), wherein R 1 is 2-t- butylpyrimidin-5-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 12 comprises 167 compounds ofthe general formula (I), wherein R 1 is 2- trifluoromethylpyrimidin-5-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 13 comprises 167 compounds of the general formula (I), wherein R 1 is 2- trifluoromethyl-4,6-dimethylpyrimidin-5-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 14 comprises 167 compounds of the general formula (I), wherein R 1 is 2,4- dimethoxypyrimidin-5-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 15 comprises 167 compounds of the general formula (I), wherein R 1 is pyridazin-3-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 16 comprises 167 compounds of the general formula (I), wherein R 1 is pyrazin- 2-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 8 comprises 167 compounds of the general formula (I), wherein R 1 is 4,6- diphenyl-l,3,5-triazin-2-yl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • the compounds of the invention may be obtained in the form of mixtures of stereoisomers, including enantiomers, diastereomers and geometric isomers. Such mixtures may be separated into individual isomers by techniques well known in the art and this invention embraces the individual isomers and mixtures thereof in all proportions. It is to be expected that one isomer may be more fungicidally active than another.
  • the compounds of formula (I) can be prepared by reacting a compound of formula (II):
  • R 1 has the meaning given above and R is, for example, C M alkyl, suitably ethyl, with a carbonylating agent, suitably l.l'-carbonyldiimidazole, in a convenient water-immiscible solvent, such as dichloromethane, at an elevated temperature, for example the reflux temperature of dichloromethane (ca 41°C).
  • a convenient water-immiscible solvent such as dichloromethane
  • the product is conveniently isolated by pouring the reaction mixture into water and separating, or extracting with a solvent, the organic phase, which is washed, dried and evaporated.
  • the product redissolved in the water-immiscible solvent, is reacted with a hydrazine of formula R 2 NHNH 2 in the presence of an acid catalyst, for example acetic acid, typically at ambient temperature.
  • an acid catalyst for example acetic acid
  • the reaction mixture may be poured into water and the organic phase extracted with a solvent or otherwise separated from the aqueous phase.
  • the organic phase is washed, for example, successively with a dilute mineral acid, such as hydrochloric acid, an aqueous base, such as sodium bicarbonate, and brine before being dried and evaporated to give the desired product in crude form.
  • the product can then be purified by the usual chromatographic techniques.
  • Carbonylating agents such as l,l'-carbonyldiimidazole, are commercially available, as are many hydrazines of formula R 2 NHNH 2 . Hydrazines of formula R 2 NHNH 2 not commercially available may be prepared by methods well documented in the literature.
  • R and R 1 have the meanings given above and X is halo, suitably chloro, in a convenient solvent, such as N,N-dimethylformamide, and in the presence of a base, such as potassium carbonate.
  • a convenient solvent such as N,N-dimethylformamide
  • a base such as potassium carbonate.
  • the desired product may be isolated by pouring the reaction mixture into water, extracting the product with a solvent, for example ethyl acetate, and washing, drying and evaporating the organic extract.
  • the product may be purified by the usual chromatographic techniques.
  • the compound RXCH 2 X is either commercially available or can be prepared by methods well documented in the literature.
  • Compounds of the formula (III) can be prepared by treating a compound of formula (III) can be prepared by treating a compound of formula (III)
  • TBDMSO t-butyldimethylsiloxy and R has the meaning given above
  • a solvent such as tetrahydrofuran
  • tetrabutylammonium fluoride a solution of tetrabutylammonium fluoride
  • Compounds of formula (IV) can be prepared by reacting the Grignard reagent formed from magnesium, iodine and 4- bromo-l-(/-butyldimethylsiloxy)benzene with sodium pyruvate in tetrahydrofuran and treating the propionic acid so formed with ethyl iodide in N,N-dimethyl formamide in the presence of diisopropylethylamine.
  • 4-Bromo- 1 -(t-butyldimethylsiloxy)benzene may be obtained by reacting 4-bromophenol with t-butyl-dimethylsilylchloride in N,N-dimethyl formamide in the presence of imidazole .
  • compounds of formula (II) may be obtained by reacting the Grignard reagent formed from magnesium and a compound of formula (V):
  • Compounds of formula (V), may be obtained by reacting 4-bromophenol with a compound of the formula R'-CH 2 X in the presence of a base such as potassium carbonate.
  • the present invention provides processes, as herein described, for preparing the compounds of formula (I).
  • the compounds of formula (I) are active fungicides and may be used to control one or more of the following pathogens: Pyricularia oryzae on rice and wheat and other Pyricularia spp. on other hosts; Puccinia recondita, Puccinia striiformis and other rusts on wheat,
  • Puccinia hordei Puccinia striiformis and other rusts on barley, and rusts on other hosts e.g. turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables and ornamental plants;
  • Erysiphe graminis on barley, wheat, rye and turf and other powdery mildews on various hosts such as Sphaerotheca macularis on hops, Sphaerotheca fuliginea on cucurbits (e.g. cucumber), Podosphaera leucotricha on apple and Uncinula necator on vines; Cochliobolus spp., Helminthosporium spp., Drechslera spp. (Pyrenophora spp.), Rhynchosporium spp., Septoria spp.
  • Ramularia spp. on sugar beet and other hosts post-harvest diseases particularly of fruit (e.g. Pencillium digitatum and P. italicum and Trichoderma viride on oranges, Colletotrichum musae and Gloeosporium musarum on bananas and Botrytis cinerea on grapes); other pathogens on vines, notably Eutypa lata, Guignardia bidwellii, Phellinus igniarus, Phomopsis viticola, Pseudopezicula tracheiphila and Stereum hirsutum; other pathogens on lumber, notably Cephaloascus fragrans, Ceratocystis spp., Ophiostoma piceae, Penicillium spp., Trichoderma pseudokoningii, Trichoderma viride, Trichoderma harzianum, Aspergillus niger, Leptographium lindbergi and
  • some of the compounds may be useful as seed dressings against pathogens including Fusarium spp., Septoria spp., Tilletia spp., (e.g. bunt, a seed-borne disease of wheat), Ustilago spp. and Helminthosporium spp. on cereals, Rhizoctonia solani on cotton and Pyricularia oryzae on rice.
  • pathogens including Fusarium spp., Septoria spp., Tilletia spp., (e.g. bunt, a seed-borne disease of wheat), Ustilago spp. and Helminthosporium spp. on cereals, Rhizoctonia solani on cotton and Pyricularia oryzae on rice.
  • the compounds may move acropetally/locally in plant tissue. Moreover, the compounds may be volatile enough to be active in the vapour phase against fungi on the plant.
  • the invention therefore provides a method of combating fungi which comprises applying to a plant, to a seed of a plant or to the locus of the plant or seed a fungicidally effective amount of a compound as hereinbefore defined, or a composition containing the same.
  • the compounds may be used directly for agricultural purposes but are more conveniently formulated into compositions using a carrier or diluent.
  • the invention thus provides fungicidal compositions comprising a compound as hereinbefore defined and an acceptable carrier or diluent therefor. It is preferred that all compositions, both solid and liquid formulations, comprise 0.0001 to 95%, more preferably 1 to 85%, for example 1 to 25% or 25 to 60%, of a compound as hereinbefore defined.
  • the compounds of the invention When applied to the foliage of plants, the compounds of the invention are applied at rates of 0. Ig to 10kg, preferably lg to 8kg, more preferably lOg to 4kg, of active ingredient (invention compound) per hectare.
  • the compounds of the invention are used at rates of O.OOOlg (for example O.OOlg or 0.05g) to lOg, preferably 0.005g to 8g, more preferably 0.005g to 4g, of active ingredient (invention compound) per kilogram of seed.
  • the compounds can be applied in a number of ways. For example, they can be applied, formulated or unformulated, directly to the foliage of a plant, to seeds or to other medium in which plants are growing or are to be planted, or they can be sprayed on, dusted on or applied as a cream or paste formulation, or they can be applied as a vapour or as slow release granules.
  • Application can be to any part of the plant including the foliage, stems, branches or roots, or to soil surrounding the roots, or to the seed before it is planted, or to the soil generally, to paddy water or to hydroponic culture systems.
  • the invention compounds may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods, or applied by land or aerial irrigation systems.
  • plant as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes preventative, protectant, prophylactic, systemic and eradicant treatments.
  • the compounds are preferably used for agricultural and horticultural purposes in the form of a composition.
  • the type of composition used in any instance will depend upon the particular purpose envisaged.
  • compositions may be in the form of dustable powders or granules comprising the active ingredient (invention compound) and a solid diluent or carrier, for example, fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous earth and china clay.
  • a solid diluent or carrier for example, fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous earth and china clay.
  • Such granules can be preformed granules suitable for application to the soil without further treatment.
  • These granules can be made either by impregnating pellets of filler with the active ingredient or by pelleting a mixture of the active ingredient and powdered filler.
  • compositions for dressing seed may include an agent (for example, a mineral oil) for assisting the adhesion of the composition to the seed; alternatively the active ingredient can be formulated for seed dressing purposes using an organic solvent (for example, N-methylpyrrolidone, propylene glycol or N,N-dimethylformamide).
  • the compositions may also be in the form of water dispersible powders or water dispersible granules comprising wetting or dispersing agents to facilitate the dispersion in liquids.
  • the powders and granules may also contain fillers and suspending agents.
  • compositions may also be in the form of soluble powders or granules, or in the form of solutions in polar solvents.
  • Soluble powders may be prepared by mixing the active ingredient with a water-soluble salt such as sodium bicarbonate, sodium carbonate, magnesium sulphate or a polysaccharide, and a wetting or dispersing agent to improve water dispersibility/solubility. The mixture may then be ground to a fine powder. Similar compositions may also be granulated to form water-soluble granules. Solutions may be prepared by dissolving the active ingredient in polar solvents such as ketones, alcohols and glycol ethers. These solutions may contain surface active agents to improve water dilution and prevent crystallisation in a spray tank.
  • Emulsifiable concentrates or emulsions may be prepared by dissolving the active ingredient in an organic solvent optionally containing a wetting or emulsifying agent and then adding the mixture to water which may also contain a wetting or emulsifying agent.
  • organic solvents are aromatic solvents such as alkylbenzenes and alkylnaphthalenes, ketones such as cyclohexanone and methylcyclohexanone, chlorinated hydrocarbons such as chlorobenzene and trichlorethane, and alcohols such as benzyl alcohol, furfuryl alcohol, butanol and glycol ethers.
  • Aqueous suspension concentrates of largely insoluble solids may be prepared by ball or bead milling with a dispersing agent with a suspending agent included to stop the solid settling.
  • Compositions to be used as sprays may be in the form of aerosols wherein the formulation is held in a container under pressure of a suitable propellant.
  • the invention compounds can be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating in enclosed spaces a smoke containing the compounds.
  • the compounds may be used in micro-encapsulated form. They may also be formulated in biodegradable polymeric formulations to obtain a slow, controlled release of the active substance.
  • additives for improving the uptake, distribution, adhesive power and resistance to rain on treated surfaces the different compositions can be better adapted for various utilities.
  • Other additives may be included to improve the biological efficacy of the various formulations.
  • Such additives can be surface active materials to improve the wetting and retention on surfaces treated with the formulation and also the uptake and mobility of the active material, or additionally can include oil based spray additives, for example, certain mineral oil and natural plant oil (such as soya bean and rape seed oil) additives, or blends of them with other adjuvants.
  • the invention compounds can be used as mixtures with fertilisers (e.g. nitrogen-, potassium- or phosphorus-containing fertilisers).
  • Compositions comprising only granules of fertiliser incorporating, for example coated with, a compound of formula (I) are preferred. Such granules suitably contain up to 25% by weight of the compound.
  • the invention therefore also provides a fertiliser composition comprising a fertiliser and the compound of general formula (I) or a salt or metal complex thereof.
  • Water dispersible powders, emulsifiable concentrates and suspension concentrates will normally contain surfactants, e.g. a wetting agent, dispersing agent, emulsifying agent or suspending agent. These agents can be cationic, anionic or non-ionic agents.
  • Suitable cationic agents are quaternary ammonium compounds, for example, cetyltrimethylammonium bromide.
  • Suitable anionic agents are soaps, salts of aliphatic monoesters of sulphuric acid (for example, sodium lauryl sulphate), and salts of sulphonated aromatic compounds (for example, sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of sodium diisopropyl- and triisopropylnaphthalene sulphonates).
  • Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcohols such as oleyl or cetyl alcohol, or with alkyl phenols such as octyl- or nonylphenol and octylcresol.
  • Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, alkyl glucosides, polysaccharides and the lecithins and the condensation products of the said partial esters with ethylene oxide.
  • Suitable suspending agents are hydrophilic colloids (for example, polyvinylpyrrolidone and sodium carboxymethylcellulose), and swelling clays such as bentonite or attapulgite.
  • compositions for use as aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being diluted with water before use.
  • These concentrates should preferably be able to withstand storage for prolonged periods and after such storage be capable of dilution with water in order to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment.
  • the concentrates may conveniently contain up to 95%, suitably 1-85%, for example 1-25% or 25-60%, by weight of the active ingredient.
  • compositions of this invention may contain other compounds having biological activity, e.g. compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal or insecticidal activity.
  • the resulting composition can have a broader spectrum of activity or a greater level of intrinsic activity than the compound of general formula (I) alone. Further the other fungicide can have a synergistic effect on the fungicidal activity of the compound of general formula (I).
  • fungicidal compounds which may be included in the composition of the invention are (£>N-methyl-2-(2-phenoxyphenyl)-2- methoxyiminoacetamide, (E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy- iminoacetamide, (R5)-l-aminopropylphosphonic acid, (RS)-4-(4-chlorophenyl)- -2-phenyl-2-( IH- 1 ,2,4-triazol- 1 -ylmethyl)butyronitrile, (Z)-N-but-2-enyloxymethyl- -2-chloro-2',6'-diethylacetanilide, 1 -(2-cyano-2-methoxyiminoacetyl)-3-ethyl urea, 4-(2,2-difluoro- 1 ,3-benzodioxol-4-yl)pyrrole-3-carbonitrile
  • Methanesulphonyl chloride (677 mg, 5.91 mmol) was to a stirred solution of 2- hydroxymethylpyrazine (500 mg, 4.5 mmol) and triethylamine (1.3 ml, 9.1 mmol) in dry dichloromethane (10 ml) at 0 °C. The solution was stirred at ambient temperature for 5 hours, then poured into water and extracted with dichloromethane. The combined organic extracts were washed with water and brine, dried and evaporated to provide a dark brown oil.
  • EXAMPLE 8 The compounds were tested against a variety of foliar fungal diseases of plants. The technique employed was as follows. The plants were grown in John Innes Potting Compost (No 1 or 2) in 4 cm diameter minipots. The test compounds were formulated either by bead milling with aqueous Dispersol T or as a solution in acetone or acetone/ethanol which was diluted to the required concentration immediately before use. The formulations (100 ppm active ingredient) were sprayed on to the foliage of the plants to a maximum retention. Tween 20 was added to give a final concentration of 0.05% when the sprays were applied to cereals.
  • the compounds were applied to the foliage (by spraying) one or two days before the plant was inoculated with the disease.
  • Foliar pathogens were applied by spray as zoosporangial suspensions onto the leaves of test plants. After inoculation, the plants were put into an appropriate environment to allow infection to proceed and then incubated until the disease was ready for assessment. The period between inoculation and assessment varied from four to fourteen days according to the disease and environment.
  • the disease level present (i.e. leaf area covered by actively sporulating disease) on each of the treated plants was recorded using the following assessment scale:
  • This calculated POCO value is then rounded to the nearest of the values in the 9-point assessment scale shown above. In this particular example, the POCO value would be rounded to 30. If the calculated POCO falls exactly mid-way between two of the points, it is rounded to the lower of the two values. The results are shown in Table 9.

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Abstract

A fungicidal oxazolidinedione compound having general formula (I) wherein R1 is a C-linked 6-membered heteroaromatic ring containing 2 or 3 nitrogen atoms and which is optionally N- or C-substituted with one or more of halo, hydroxy, oxo, C¿1-6? alkyl, C3-6 cycloalkyl, halo(C1-6)alkyl, C1-4 alkoxy(C1-6)alkyl, aryl(C1-6)alkyl, C1-6 alkoxy, halo(C1-6)alkoxy, C2-4 alkenyloxy, C1-6 alkylthio, C1-6 alkylcarbonyl, C1-6 alkylcarbonylamino, C1-6 alkoxycarbonyl, arylcarbonyl, aryl, aryloxy, or heteroaryl, the aryl and heteroaryl substituents themselves being optionally substituted with one or more of halo, C1-6 alkyl, halo(C1-6)alkyl, C1-6 alkoxy, halo(C1-6)alkoxy, C1-4 alkoxy (C1-6) alkyl, nitro, amino, mono- or di(C1-4)alkylamino, cyano, C1-6 alkoxycarbonyl or C1-6 alkylcarbonyl, and R?2¿ is phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, thiadiazolyl, oxadiazolyl or tetrazolyl, any of which is optionally substituted with one or more of halo, C¿1-6? alkyl, halo(C1-6)alkyl, C1-6 alkoxy, halo(C1-6)alkoxy, C1-6 alkylthio, nitro, cyano, thiocyanato, C1-4 alkylsulphonyl, halo(C1-4)alkylsulphonyl, aminosulphonyl or C1-6 alkoxycarbonyl, or two adjacent substituents join to form with the carbon atoms to which they are attached a fused benzene ring optionally substituted with halo, C1-4 alkyl or C1-4 alkoxy.

Description

FUNGTCIDAL OXAZOLIDINEDIONE DERIVATIVES
The present invention relates to novel oxazolidinedione derivatives, to processes for preparing them, to fungicidal compositions containing them and to methods of using them to combat fungi, especially fungal infections of plants.
The antifungal properties of certain oxazolidinedione derivatives are described in the literature. By way of example, reference is made to EP-A-0393911, WO 93/18016, WO 93/22299, JP-A-6220049 and US Statutory Invention Registration No. HI 401.
According to the present invention there is provided a compound of the general formula (I):
Figure imgf000003_0001
wherein R1 is a C-linked 6-membered heteroaromatic ring containing 2 or 3 nitrogen atoms and which is optionally N- or C-substituted with one or more of halo, hydroxy, oxo, Cι-6 alkyl, C3.6 cycloalkyl, halo(Cι.6)alkyl, Cι-4 alkoxy(Cι.6)alkyl, aryl(Cι-6)alkyl, Ci.6 alkoxy, halo(Cι.6)alkoxy, C2.4 alkenyloxy, d_6 alkylthio, Cι-6 alkylcarbonyl, Cι.6 alkylcarbonylamino, Ci.6 alkoxycarbonyl, arylcarbonyl, aryl, aryloxy, or heteroaryl, the aryl and heteroaryl substituents themselves being optionally substituted with one or more of halo, Cι.6 alkyl, halo(Cι.6)alkyl, C|.6 alkoxy, halo(C].6)alkoxy, Cι-4 alkoxy Cι.6 alkyl, nitro, amino, mono- or di(Cι.4)alkylamino, cyano, Cι.6 alkoxycarbonyl or C|.6 alkylcarbonyl, and R2 is phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, thiadiazolyl, oxadiazolyl or tetrazolyl, any of which is optionally substituted with one or more of halo, Cι-6 alkyl, halo(C[.6)alkyl, C|.6 alkoxy, halo(Cι-6)alkoxy, Cι.6 alkylthio, nitro, cyano, thiocyanato, CM alkylsulphonyl, halo(Cι.4)alkylsulphonyl, aminosulphonyl or Cι.6 alkoxycarbonyl or, two adjacent substituents join to form with the carbon atoms to which they are attached a fused benzene ring optionally substituted with halo, Cι.4 alkyl or Cι-4 alkoxy.
Unless otherwise stated, all alkyl moieties, including the alkyl moieties of haloalkyl, alkoxy, alkylthio, alkylsulphonyl, etc., suitably contain from 1 to 6 , for example from 1 to 4, carbon atoms in the form of straight or branched chains. Examples are methyl, ethyl, n- and wo-propyl, n-, sec-, iso- and tert-butyl and n-hexyl. C3.6 cycloalkyl includes cyclopropyl and cyclohexyl.
Halo includes fluoro, chloro, bromo and iodo. Most commonly it is fluoro or chloro. Haloalkyl is typically trifluoromethyl and haloalkoxy is typically trifluoromethoxy. Aryl is usually phenyl but also includes naphthyl.
Heteroaryl includes the residues of 6-membered heteroaromatic rings containing from 1 to 3 N atoms, eg pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl or 1,3,5-triazinyl, and the residues of 5-membered heteroaromatic rings containing 1 to 3 heteroatoms selected from N, O and S, eg furyl, thienyl, pyrrolyl, thiazolyl, oxazolyl, isothiazolyl, isoxazolyl, pyrazolyl, imidazolyl, thiadiazolyl, oxadiazolyl or triazolyl. Typically heteroaryl is pyridyl, thienyl, furyl, pyrrolyl, isoxazolyl or isothiazolyl.
The 6-membered heteroaromatic ring R1 is selected from pyrimidinyl, pyrazinyl, pyridazinyl and 1,2,4- and 1,3,5-triazinyl. Typically R1 is 2-pyrimidinyl, 4-pyrimidinyl, 5- pyrimidinyl, 2-pyrazinyl, 3 -pyridazinyl, or 2-( 1,3,5-triazinyl) optionally N- or C-substituted with one or more of the R1 substituents listed above.
Of particular interest are compounds in which R1 is 2-pyrimidinyl optionally substituted with hydroxy, oxo, CM alkyl, C3.6 cycloalkyl, halo(C|.4)alkyl, C|.4 alkoxy, halo(C].4)alkoxy or C2-4 alkenyloxy; 4-pyrimidinyl optionally substituted in the 2-position with CM alkyl, C3-6 cycloalkyl, halo(Cι-4)alkyl, CM alkoxy, halo(CM)alkoxy, CM alkylthio, aryl, aryl(C|.4)alkyl or heteroaryl and in the 5- and 6-positions with hydroxy, CM alkyl, C3.6 cycloalkyl, halo(Cι-4)alkyl, CM alkoxy or halo(Cι.4)alkoxy; 5-pyrimidinyl optionally substituted in the 2-position with CM alkyl, C3.6 cycloalkyl, halo(Cι.4)alkyl, CM alkoxy, halo(Cι.4)alkoxy, CM alkylthio, aryl or heteroaryl and in the 4- and 6-positions with CM alkyl, C3.6 cycloalkyl, halo(Q.4)alkyl, CM alkoxy or halo(CM)alkoxy; 1,3,5-triazinyl optionally substituted with CM alkyl, halo(Cι-4)alkyl, C].4 alkoxy or aryl; 3-(l,2,4-triazinyl) optionally substituted with CM alkyl, halo(Cι-4)alkyl, CM alkoxy or aryl; 5- (1,2,4-triazinyl) optionally substituted with Cι.4 alkyl, halo(Cι-4)alkyl, C|.4 alkoxy or aryl; 6-( 1 ,2,4-triazinyl) optionally substituted with Cι.4 alkyl, halo(Cι.4)alkyl, CM alkoxy or aryl; 3-pyridazinyl optionally substituted with CM alkyl, halo(Ci.4)alkyl, C,.4 alkoxy or aryl; 4-pyridazinyl optionally substituted with C)-4 alkyl, halo (Cι.4)alkyl, C1-4 alkoxy or aryl; or 2-pyrazinyl optionally substituted with d.4 alkyl, halo(Cι.4) alkyl, C,.4 alkoxy or aryl. The aryl or heteroaryl substituent of the 6-membered heteroaromatic ring R1 may be any aryl or heteroaryl group defined above and may be optionally substituted with one or more of halo, CM alkyl, halo(Cι.4)alkyl, CM alkoxy, halo(Cι.4)alkoxy, CM alkoxy (Cι.4)alkyl, nitro, amino, mono- or di(CM)alkylamino, cyano, CM alkoxycarbonyl or C|.4 alkylcarbonyl.
The group R2 is typically unsubstituted phenyl but may also be phenyl substituted with a bromine or iodine atom, with 1 to 5 chlorine or fluorine atoms, with 4 chlorine or fluorine atoms and a methyl or trifluoromethyl group or with 1 to 3 substituents selected from halo, CM alkyl, halo(Cι.4)alkyl, CM alkoxy, halo(Cι.4)alkoxy, CI-4 alkylthio, nitro, cyano, thiocyanato, CM alkylsulphonyl, halo(Cι.4)alkylsulphonyl, aminosulphonyl or C)-4 alkoxycarbonyl, or naphthyl. Alternatively, R2 is, for example, 2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 3-pyridazinyl, 3-thienyl, 3- or 5-pyrazolyl, 2-thiazolyl, 3-(l,2,4-triazolyl), 5- (1,2,3-thiadiazolyl) or 5-tetrazolyl, any of which is optionally substituted with 1 to 3 substituents selected from halo, C|.4 alkyl, halo(Cι.4)alkyl, CM alkoxy, halo(Cι.4)alkoxy, nitro, cyano, phenyl, CM alkylsulphonyl or Cι-4 alkoxycarbonyl or, in the case of pyridyl, with 4 fluorine or chlorine atoms. As a further alternative R2 is, for example, 2-, 3- or 4-quinolinyl, 4-quinazolinyl, 1- phthalazinyl, 2-quinoxalinyl, 3-(l,2,4-benzotriazinyl), 2-benzoxazolyl or 2-benzothiazolyl, any of which is optionally substituted in its fused benzene ring with halo, CM alkyl, CM alkoxy or nitro and in its heterocyclic ring with halo, CM alkyl, halo(C|.4)alkyl, CM alkoxy, halo(Cι. 4)alkoxy, nitro, cyano, CM alkylsulphonyl or Cι-4 alkoxycarbonyl. The present invention is illustrated by the compounds of general formula (I) listed in
Tables 1 to 17 which follow.
TABLE 1
Table 1 comprises 167 compounds of the general formula (I), wherein R' is 4-methyl- 6-hydroxypyrimidin-2-yl and R2 has the value listed below.
Compound Compound
No. B! No. £
1 C6H5 26 3-Cl-4-Br-C6H3
2 2-F-C6H4 27 2,3,4-F3-C6H2
3 3-F-C6H4 28 2,4,6-F3-C6H2
4 4-F-C6H4 29 2,3,4-Cl3-C6H2
5 2-Cl-C6H4 30 2,4,6-Cl3-C6H2
6 3-Cl-C6H4 31 2,3,5,6-F4-C6H
7 4-Cl-C6H4 32 2,3,5,6-Cl4-C6H
8 2-Br-C6H4 33 C6F5
Figure imgf000006_0001
10 4-Br-C6H4 35 2-CH3-CήH4
11 4-I-C6H4 36 3-CH3-C0H4
12 2,3-F2-CeH3 37 4-CH3-C6H4
13 2,4-F2-C6H3 38 2-C2H5-C6H4
14 2,5-F2-C6H3 39 3-C2H5-C0H4
15 2,6-F2-C6H3 40 4-C2H5-C6H4
16 3,4-F2-C6H3 41 4-CH(CH3)2-C6H4
17 3,5-F2-C6H3 42 4-C(CH3)3-C6H4
18 2,3-Cl2-C6H3 43 2,3-(CH3)2-C6H3
19 2,4-Cl2-C6H3 44 2,4-(CH3)2-C6H3
20 2,5-Cl2-C6H3 45 2,5-(CH3)2-C6H3
21 2,6-Cl2-C6H3 46 2,6-(CH3)2-C6H3
22 3,4-Cl2-C6H3 47 3,4-(CH3)2-C6H3
23 3,5-Cl2-C0H3 48 3,5-(CH3)2-C6H3
24 2-F-6-Cl-C6H3 49 2,6-(C2Hs)2-C6H3
25 3-Cl-4-F-C6H3 50 2,4,6-(CH3)3-C6H2 Compound Compound No. R? No. Rf
51 2-Cl-4-CH3-C6H, 80 2,4-Cl2-6-CF3-C6H2
52 2-Cl-5-CH3-C6Hι 81 2,6-F2-4-CF3-C6H2
53 2-Cl-6-CH,-C6H3 82 2,6-Cl2-4-CF3-C6H2
54 3-Cl-4-CH3-C6H3 83 2,3,5,6-F4-4-CF3-C0
55 2-CH3-4-Cl-C6H, 84 2,3,5,6-Cl4-4-CF3-C6
56 2-CH3-5-F-C6H3 85 2-OCH3-C6H4
57 2,4-F2-6-CHrC6H2 86 3-OCH3-C6H4
58 2,4-Cl2-6-CH3-C6H2 87 4-OCH3-C6H4
59 2,6-F2-4-CH3-C6H2 88 2-SCH3-C6H4
60 2,6-Cl2-4-CH3-C6H2 89 3-SCH3-C0H4
61 2,3,5,6-F4-4-CH3-C6 90 4-SCH3-C6H4
62 2,3,5,6-Cl4-4-CH3-C6 91 2-SCH3-5-CF3-C6H3
Figure imgf000007_0001
64 3-CF3-C6H4 93 2-NO2-C6H4
65 4-CF3-C6H4 94 3-NO2-C6H4
66 2,3-(CF3)2-C6H3 95 4-NO2-C6H4
67 2,4-(CF3)2-C6H3 96 2,4-(NO2)2-C6H3
68 2,5-(CF3)2-C6H3 97 2,6-(NO2)2-C6H3
69 2,6-(CF3)2-C6H3 98 2-NO2-4-Cl-C6H3
70 3,4-(CF3)2-C6H3 99 2,6-(NO2)2-4-CF3-C6H2
71 3,5-(CF3)2-C6H3 100 2-NO2-4-CF3-5-Cl-C6H2
72 2,4,6-(CF3)2-C6H3 101 2-CN-C6H4
73 2-Cl-4-CF3-C6H3 102 3-CN-C6H4
74 2-Cl-5-CF3-C6H3 103 4-CN-C6H4
75 2-Cl-6-CF3-C6H3 104 2-CN-3-F-C6H3
76 3-Cl-4-CF3-C6H3 105 2-NO2-4-CN-C6H3
77 2-CF3-4-Cl-C6H3 106 2-CN-3-Cl-C6H3
78 2-CF3-5-Cl-C6H3 107 4-SCN-C6H4
79 2,4-F2-6-CF3-C6H2 108 4-SO2CH3-C6H4 Compound Compound
No. Bl No. Bi
109 2-Cl-4-SO2CH3-C6H3 131 2,3,5,6-Cl4-pyrid-4-yl
110 2-Cl-5-SO2CH3-C6H3 132 2,5,6-F3-3-Cl-pyrid-4-yl
1 1 1 2-Cl-4-SO2CHF2-C6H3 133 quinolin-2-yl
112 2-NO2-4-SO2CH3-C6H3 134 quinolin-3-yl
1 13 2-NO2-4-SO2CHF2-C6H3 135 quinolin-4-yl
1 14 2-NO:-4-SO2CF2CHFCl- 136 7-Cl-quinolin-4-yl
Figure imgf000008_0001
115 4-SO2NH2-C6U, 137 2-CH3-6-OCH3-quinoIin-4-yl
1 16 2-CO2CH3-C6rI4 138 pyrimidin-2-yl
1 17 naphth-1-yl 139 pyrimidin-4-yl
1 18 pyrid-2-yl 140 pyrimidin-5-yl
119 pyrid-3-yl 141 4-CF3-pyrimidin-2-yl
120 pyrid-4-yl 142 2,6-(CH3)2-pyrimidin-4-yl
121 5-CF3-pyrid-2-yl 143 4,6-(CH3)2-pyrimidin-2-yl
122 6-CF3-pyrid-2-yl 144 4-CF3-5-CO2CH3-pyrimidin-2-yl
123 3-NO2-pyrid-2-yl 145 6-Cl-quinazolin-4-yl
124 5-NO2-pyrid-2-yl 146 pyridazin-3-yl
125 3-Cl-5-CF3-pyrid-2-yl 147 6-CH3-pyridazin-3-yl
126 3,5-Cl2-pyrid-2-yl 148 phthalazin-1-yl
127 3,5-(CF3)2-pyrid-2-yl 149 3-Cl-quinoxalin-2-yl
128 4-CF3-6-CH3-pyrid-2-yl 150 3,7-Cl2-quinoxalin-2-yl
129 2-CCl3-3,5-Cl2-pyrid-4-yl 151 1 ,2,4-benzotriazin-3-yl
130 3-CN-4,6-(CH3)2-pyrid-2- 152 7-OCH3-l ,2,4-benzotriazin-3-yl yi
153 2-CO2CH3-thien-3-yl 160 4-C6H5-thiazol-2-yl
154 2-CO2CH3-4-CH3-thien- 161 5-CH3-l,2,4-triazol-3-yl 3-yl
155 2-CO2CH3-4-SO2- 162 4-CO2C2H5- 1 ,2,3-thiadiazol-5-yl CH(CH3)2-thien-3-yl
156 2-CO2CH3-4-SO2C3Hϊ- 163 tetrazol-5-yl thien-3-yl
157 4-CO2C2H5-5-CH3- 164 benzoxazol-2-yl pyrazol-3-yl
158 3-CH3-4-CO2C2H5- 165 benzothiazol-2-yl pyrazol-5-yl
159 l,3-(CH3)2-4-NO2- 166 4-CHrbenzothiazoI-2-yl pyrazol-5-yI
167 6-NO2-benzothiazol-2-yl
TABLE 2
Table 2 comprises 167 compounds of the general formula (I), wherein R1 is 4- methoxy-6-methylpyrimidin-2-yl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 3 Table 3 comprises 167 compounds of the general formula (I), wherein R' is 4- allyloxy-6-methylpyrimidin-2-yl and R2 has the value listed for the correspondingly numbered compound in Table 1. TABLE 4
Table 4 comprises 167 compounds of the general formula (I), wherein R1 is 4,6- dimethoxypyrimidin-2-yl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 5 Table 5 comprises 167 compounds of the general formula (I), wherein R1 is 4,6- dimethylpyrimidin-2-yl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 6 Table 6 comprises 167 compounds of the general formula (I), wherein R1 is 1,4- dimethyl-6-oxopyrimidin-2-yl and R2 has the value listed for the correspondingly numbered compound in Table 1. TABLE 7
Table 7 comprises 167 compounds of the general formula (I), wherein R' is 2- wopropyl-6-hydroxypyrimidin-4-yl and R2 has the value listed for the correspondingly numbered compound in Table 1. TABLE 8
Table 8 comprises 167 compounds of the general formula (I), wherein R1 is 2-(5- trifluoromethylpyrid-2-yl)-6-methylpyrimidin-4-yl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 9
Table 9 comprises 167 compounds of the general formula (I), wherein R1 is pyrimidin- 5-yl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 10 Table 10 comprises 167 compounds ofthe general formula (I), wherein R1 is 2- methylpyrimidin-5-yl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 11 Table 11 comprises 167 compounds of the general formula (I), wherein R1 is 2-t- butylpyrimidin-5-yl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 12 Table 12 comprises 167 compounds ofthe general formula (I), wherein R1 is 2- trifluoromethylpyrimidin-5-yl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 13 Table 13 comprises 167 compounds of the general formula (I), wherein R1 is 2- trifluoromethyl-4,6-dimethylpyrimidin-5-yl and R2 has the value listed for the correspondingly numbered compound in Table 1. TABLE 14
Table 14 comprises 167 compounds of the general formula (I), wherein R1 is 2,4- dimethoxypyrimidin-5-yl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 15 Table 15 comprises 167 compounds of the general formula (I), wherein R1 is pyridazin-3-yl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 16 Table 16 comprises 167 compounds of the general formula (I), wherein R1 is pyrazin- 2-yl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 17 Table 8 comprises 167 compounds of the general formula (I), wherein R1 is 4,6- diphenyl-l,3,5-triazin-2-yl and R2 has the value listed for the correspondingly numbered compound in Table 1.
The compounds of the invention may be obtained in the form of mixtures of stereoisomers, including enantiomers, diastereomers and geometric isomers. Such mixtures may be separated into individual isomers by techniques well known in the art and this invention embraces the individual isomers and mixtures thereof in all proportions. It is to be expected that one isomer may be more fungicidally active than another.
The compounds of formula (I) can be prepared by reacting a compound of formula (II):
Figure imgf000011_0001
in which R1 has the meaning given above and R is, for example, CM alkyl, suitably ethyl, with a carbonylating agent, suitably l.l'-carbonyldiimidazole, in a convenient water-immiscible solvent, such as dichloromethane, at an elevated temperature, for example the reflux temperature of dichloromethane (ca 41°C). The product is conveniently isolated by pouring the reaction mixture into water and separating, or extracting with a solvent, the organic phase, which is washed, dried and evaporated.
The product, redissolved in the water-immiscible solvent, is reacted with a hydrazine of formula R2 NHNH2 in the presence of an acid catalyst, for example acetic acid, typically at ambient temperature. At the end of reaction, the reaction mixture may be poured into water and the organic phase extracted with a solvent or otherwise separated from the aqueous phase. The organic phase is washed, for example, successively with a dilute mineral acid, such as hydrochloric acid, an aqueous base, such as sodium bicarbonate, and brine before being dried and evaporated to give the desired product in crude form. The product can then be purified by the usual chromatographic techniques.
Carbonylating agents, such as l,l'-carbonyldiimidazole, are commercially available, as are many hydrazines of formula R2NHNH2. Hydrazines of formula R2NHNH2 not commercially available may be prepared by methods well documented in the literature.
Compounds of formula II can be prepared by reacting a compound of formula (III):
Figure imgf000012_0001
with a compound of the formula R'-CH2X, in which R and R1 have the meanings given above and X is halo, suitably chloro, in a convenient solvent, such as N,N-dimethylformamide, and in the presence of a base, such as potassium carbonate. The desired product may be isolated by pouring the reaction mixture into water, extracting the product with a solvent, for example ethyl acetate, and washing, drying and evaporating the organic extract. The product may be purified by the usual chromatographic techniques. The compound RXCH2X is either commercially available or can be prepared by methods well documented in the literature. Compounds of the formula (III) can be prepared by treating a compound of formula
(IV):
Figure imgf000012_0002
in which TBDMSO is t-butyldimethylsiloxy and R has the meaning given above, in a solvent, such as tetrahydrofuran, with a solution of tetrabutylammonium fluoride, and the product solvent-extracted after pouring the reaction mixture into water. Compounds of formula (IV) can be prepared by reacting the Grignard reagent formed from magnesium, iodine and 4- bromo-l-(/-butyldimethylsiloxy)benzene with sodium pyruvate in tetrahydrofuran and treating the propionic acid so formed with ethyl iodide in N,N-dimethyl formamide in the presence of diisopropylethylamine. 4-Bromo- 1 -(t-butyldimethylsiloxy)benzene may be obtained by reacting 4-bromophenol with t-butyl-dimethylsilylchloride in N,N-dimethyl formamide in the presence of imidazole .
Alternatively, compounds of formula (II) may be obtained by reacting the Grignard reagent formed from magnesium and a compound of formula (V):
Figure imgf000013_0001
with ethylpyruvate. Compounds of formula (V), may be obtained by reacting 4-bromophenol with a compound of the formula R'-CH2X in the presence of a base such as potassium carbonate.
Further information about the general chemistry involved in preparing the compounds of the invention, and other methods which may be adapted for use in preparing them, can be found in EP-A-0393911 and US Statutory Invention Registration No. H1401.
In yet a further aspect, the present invention provides processes, as herein described, for preparing the compounds of formula (I).
The compounds of formula (I) are active fungicides and may be used to control one or more of the following pathogens: Pyricularia oryzae on rice and wheat and other Pyricularia spp. on other hosts; Puccinia recondita, Puccinia striiformis and other rusts on wheat,
Puccinia hordei, Puccinia striiformis and other rusts on barley, and rusts on other hosts e.g. turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables and ornamental plants;
Erysiphe graminis (powdery mildew) on barley, wheat, rye and turf and other powdery mildews on various hosts such as Sphaerotheca macularis on hops, Sphaerotheca fuliginea on cucurbits (e.g. cucumber), Podosphaera leucotricha on apple and Uncinula necator on vines; Cochliobolus spp., Helminthosporium spp., Drechslera spp. (Pyrenophora spp.), Rhynchosporium spp., Septoria spp. (including Mycosphaerella graminicola and Leptosphaeria nodorum), Pseudocercosporella herpotrichoides and Gaeumannomyces graminis on cereals (e.g. wheat, barley, rye), turf and other hosts; Cercospora arachidicola and Cercosporidium personatum on peanuts and other Cercospora species on other hosts, for example, sugar beet, bananas, soya beans and rice; Botrytis cinerea (grey mould) on tomatoes, strawberries, vegetables, vines and other hosts and other Botrytis spp. on other hosts; Alternaria spp. on vegetables (e.g. cucumber), oil-seed rape, apples, tomatoes, cereals (e.g. wheat) and other hosts; Venturia spp. (including Venturia inaequalis (scab)) on apples, pears, stone fruit, tree nuts and other hosts; Cladosporium spp. on a range of hosts including cereals (e.g. wheat); Monilinia spp. on stone fruit, tree nuts and other hosts; Didymella spp. on tomatoes, turf, wheat and other hosts; Phoma spp. on oil-seed rape, turf, rice, potatoes, wheat and other hosts; Aspergillus spp. and Aureobasidium spp. on wheat, lumber and other hosts; Ascochyta spp. on peas, wheat, barley and other hosts; Plasmopara viticola on vines; other downy mildews such as Bremia lactucae on lettuce, Peronospora spp. on soybeans, tobacco, onions and other hosts, Pseudoperonospora humuli on hops and Pseudoperonospora cubensis on cucurbits; Pythium spp. (including Pythium ultimum) on turf and other hosts; Phytophthora infestans on potatoes and tomatoes and other Phytophthora spp. on vegetables, strawberries, avocado, pepper, ornamentals, tobacco, cocoa and other hosts; Thanatephorus cucumeris on rice and turf and other Rhizoctonia species on various hosts such as wheat and barley, vegetables, cotton and turf; Sclerotinia spp. on turf, peanuts, oil-seed rape and other hosts; Sclerotium spp. on turf, peanuts and other hosts; Colletotrichum spp. on a range of hosts including turf, coffee and vegetables; Laetisaria fuciformis on turf; Mycosphaerella spp. on banana, peanut, citrus, pecan, papaya and other hosts; Diaporthe spp. on citrus, soybean, melon, pear, lupin and other hosts; Elsinoe spp. on citrus, vines, olives, pecans, roses and other hosts; Pyrenopeziza spp. on oil-seed rape and other hosts; Oncobasidium theobromae on cocoa causing vascular streak dieback; Fusarium spp., Typhula spp., Microdochium nivale, Ustilago spp., Urocystis spp., Tilletia spp., and Claviceps purpurea on a variety of hosts but particularly wheat, barley, turf and maize;
Ramularia spp. on sugar beet and other hosts; post-harvest diseases particularly of fruit (e.g. Pencillium digitatum and P. italicum and Trichoderma viride on oranges, Colletotrichum musae and Gloeosporium musarum on bananas and Botrytis cinerea on grapes); other pathogens on vines, notably Eutypa lata, Guignardia bidwellii, Phellinus igniarus, Phomopsis viticola, Pseudopezicula tracheiphila and Stereum hirsutum; other pathogens on lumber, notably Cephaloascus fragrans, Ceratocystis spp., Ophiostoma piceae, Penicillium spp., Trichoderma pseudokoningii, Trichoderma viride, Trichoderma harzianum, Aspergillus niger, Leptographium lindbergi and Aureobasidium pullulans; and fungal vectors of viral diseases e.g. Polymyxa graminis on cereals as the vector of barley yellow mosaic virus (BYMV).
Further, some of the compounds may be useful as seed dressings against pathogens including Fusarium spp., Septoria spp., Tilletia spp., (e.g. bunt, a seed-borne disease of wheat), Ustilago spp. and Helminthosporium spp. on cereals, Rhizoctonia solani on cotton and Pyricularia oryzae on rice.
The compounds may move acropetally/locally in plant tissue. Moreover, the compounds may be volatile enough to be active in the vapour phase against fungi on the plant. The invention therefore provides a method of combating fungi which comprises applying to a plant, to a seed of a plant or to the locus of the plant or seed a fungicidally effective amount of a compound as hereinbefore defined, or a composition containing the same.
The compounds may be used directly for agricultural purposes but are more conveniently formulated into compositions using a carrier or diluent. The invention thus provides fungicidal compositions comprising a compound as hereinbefore defined and an acceptable carrier or diluent therefor. It is preferred that all compositions, both solid and liquid formulations, comprise 0.0001 to 95%, more preferably 1 to 85%, for example 1 to 25% or 25 to 60%, of a compound as hereinbefore defined.
When applied to the foliage of plants, the compounds of the invention are applied at rates of 0. Ig to 10kg, preferably lg to 8kg, more preferably lOg to 4kg, of active ingredient (invention compound) per hectare.
When used as seed dressings, the compounds of the invention are used at rates of O.OOOlg (for example O.OOlg or 0.05g) to lOg, preferably 0.005g to 8g, more preferably 0.005g to 4g, of active ingredient (invention compound) per kilogram of seed. The compounds can be applied in a number of ways. For example, they can be applied, formulated or unformulated, directly to the foliage of a plant, to seeds or to other medium in which plants are growing or are to be planted, or they can be sprayed on, dusted on or applied as a cream or paste formulation, or they can be applied as a vapour or as slow release granules.
Application can be to any part of the plant including the foliage, stems, branches or roots, or to soil surrounding the roots, or to the seed before it is planted, or to the soil generally, to paddy water or to hydroponic culture systems. The invention compounds may also be injected into plants or sprayed onto vegetation using electrodynamic spraying techniques or other low volume methods, or applied by land or aerial irrigation systems.
The term "plant" as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method of the invention includes preventative, protectant, prophylactic, systemic and eradicant treatments.
The compounds are preferably used for agricultural and horticultural purposes in the form of a composition. The type of composition used in any instance will depend upon the particular purpose envisaged.
The compositions may be in the form of dustable powders or granules comprising the active ingredient (invention compound) and a solid diluent or carrier, for example, fillers such as kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, fuller's earth, gypsum, diatomaceous earth and china clay. Such granules can be preformed granules suitable for application to the soil without further treatment. These granules can be made either by impregnating pellets of filler with the active ingredient or by pelleting a mixture of the active ingredient and powdered filler. Compositions for dressing seed may include an agent (for example, a mineral oil) for assisting the adhesion of the composition to the seed; alternatively the active ingredient can be formulated for seed dressing purposes using an organic solvent (for example, N-methylpyrrolidone, propylene glycol or N,N-dimethylformamide). The compositions may also be in the form of water dispersible powders or water dispersible granules comprising wetting or dispersing agents to facilitate the dispersion in liquids. The powders and granules may also contain fillers and suspending agents.
The compositions may also be in the form of soluble powders or granules, or in the form of solutions in polar solvents. Soluble powders may be prepared by mixing the active ingredient with a water-soluble salt such as sodium bicarbonate, sodium carbonate, magnesium sulphate or a polysaccharide, and a wetting or dispersing agent to improve water dispersibility/solubility. The mixture may then be ground to a fine powder. Similar compositions may also be granulated to form water-soluble granules. Solutions may be prepared by dissolving the active ingredient in polar solvents such as ketones, alcohols and glycol ethers. These solutions may contain surface active agents to improve water dilution and prevent crystallisation in a spray tank. Emulsifiable concentrates or emulsions may be prepared by dissolving the active ingredient in an organic solvent optionally containing a wetting or emulsifying agent and then adding the mixture to water which may also contain a wetting or emulsifying agent. Suitable organic solvents are aromatic solvents such as alkylbenzenes and alkylnaphthalenes, ketones such as cyclohexanone and methylcyclohexanone, chlorinated hydrocarbons such as chlorobenzene and trichlorethane, and alcohols such as benzyl alcohol, furfuryl alcohol, butanol and glycol ethers.
Aqueous suspension concentrates of largely insoluble solids may be prepared by ball or bead milling with a dispersing agent with a suspending agent included to stop the solid settling. Compositions to be used as sprays may be in the form of aerosols wherein the formulation is held in a container under pressure of a suitable propellant.
The invention compounds can be mixed in the dry state with a pyrotechnic mixture to form a composition suitable for generating in enclosed spaces a smoke containing the compounds. Alternatively, the compounds may be used in micro-encapsulated form. They may also be formulated in biodegradable polymeric formulations to obtain a slow, controlled release of the active substance.
By including suitable additives, for example additives for improving the uptake, distribution, adhesive power and resistance to rain on treated surfaces, the different compositions can be better adapted for various utilities. Other additives may be included to improve the biological efficacy of the various formulations. Such additives can be surface active materials to improve the wetting and retention on surfaces treated with the formulation and also the uptake and mobility of the active material, or additionally can include oil based spray additives, for example, certain mineral oil and natural plant oil (such as soya bean and rape seed oil) additives, or blends of them with other adjuvants.
The invention compounds can be used as mixtures with fertilisers (e.g. nitrogen-, potassium- or phosphorus-containing fertilisers). Compositions comprising only granules of fertiliser incorporating, for example coated with, a compound of formula (I) are preferred. Such granules suitably contain up to 25% by weight of the compound. The invention therefore also provides a fertiliser composition comprising a fertiliser and the compound of general formula (I) or a salt or metal complex thereof. Water dispersible powders, emulsifiable concentrates and suspension concentrates will normally contain surfactants, e.g. a wetting agent, dispersing agent, emulsifying agent or suspending agent. These agents can be cationic, anionic or non-ionic agents.
Suitable cationic agents are quaternary ammonium compounds, for example, cetyltrimethylammonium bromide. Suitable anionic agents are soaps, salts of aliphatic monoesters of sulphuric acid (for example, sodium lauryl sulphate), and salts of sulphonated aromatic compounds (for example, sodium dodecylbenzenesulphonate, sodium, calcium or ammonium lignosulphonate, butylnaphthalene sulphonate, and a mixture of sodium diisopropyl- and triisopropylnaphthalene sulphonates).
Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcohols such as oleyl or cetyl alcohol, or with alkyl phenols such as octyl- or nonylphenol and octylcresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, alkyl glucosides, polysaccharides and the lecithins and the condensation products of the said partial esters with ethylene oxide. Suitable suspending agents are hydrophilic colloids (for example, polyvinylpyrrolidone and sodium carboxymethylcellulose), and swelling clays such as bentonite or attapulgite.
Compositions for use as aqueous dispersions or emulsions are generally supplied in the form of a concentrate containing a high proportion of the active ingredient, the concentrate being diluted with water before use. These concentrates should preferably be able to withstand storage for prolonged periods and after such storage be capable of dilution with water in order to form aqueous preparations which remain homogeneous for a sufficient time to enable them to be applied by conventional spray equipment. The concentrates may conveniently contain up to 95%, suitably 1-85%, for example 1-25% or 25-60%, by weight of the active ingredient. After dilution to form aqueous preparations, such preparations may contain varying amounts of the active ingredient depending upon the intended purpose, but an aqueous preparation containing 0.0001 to 10%, for example 0.005 to 10%, by weight of active ingredient may be used. The compositions of this invention may contain other compounds having biological activity, e.g. compounds having similar or complementary fungicidal activity or which possess plant growth regulating, herbicidal or insecticidal activity.
By including another fungicide, the resulting composition can have a broader spectrum of activity or a greater level of intrinsic activity than the compound of general formula (I) alone. Further the other fungicide can have a synergistic effect on the fungicidal activity of the compound of general formula (I). Examples of fungicidal compounds which may be included in the composition of the invention are (£>N-methyl-2-(2-phenoxyphenyl)-2- methoxyiminoacetamide, (E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy- iminoacetamide, (R5)-l-aminopropylphosphonic acid, (RS)-4-(4-chlorophenyl)- -2-phenyl-2-( IH- 1 ,2,4-triazol- 1 -ylmethyl)butyronitrile, (Z)-N-but-2-enyloxymethyl- -2-chloro-2',6'-diethylacetanilide, 1 -(2-cyano-2-methoxyiminoacetyl)-3-ethyl urea, 4-(2,2-difluoro- 1 ,3-benzodioxol-4-yl)pyrrole-3-carbonitrile, 4-bromo-2-cyano-N,N-dimethyl- -6-trifluoromethylbenzimidazoIe- 1 -sulphonamide, 5-ethyl-5,8-dihydro-8-oxo( 1 ,3)-dioxol- (4,5-g)quinoline-7-carboxylic acid, α-[N-(3-chloro-2,6-xylyl)-2-methoxy- acetamido]-γ-butyrolactone, N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide, alanycarb, aldimorph, ampropylfos, anilazine, azaconazole, azoxystrobin, benalaxyl, benomyl, biloxazol, binapacryl, bitertanol, blasticidin S, bromuconazole, bupirimate, butenachlor, buthiobate, captafol, captan, carbendazim, carbendazim chlorhydrate, carboxin, CGA 245704, chinomethionate, chlorbenzthiazone, chloroneb, chlorothalonil, chlorozolinate, clozylacon, copper containing compounds such as copper oxychloride, copper oxyquinolate, copper sulphate, copper tallate, and Bordeaux mixture, cycloheximide, cymoxanil, cyproconazole, cyprodinyl, cyprofuram, debacarb, di-2-pyridyl disulphide l,l'-dioxide, dichlofluanid, dichlone, diclobutrazol, diclomezine, dicloran, didecyl dimethyl ammonium chloride, diethofencarb, difenoconazole, diflumetorim, 0,0-di-wo-propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole, dimethomoφh, dimethirimol, diniconazole, dinocap, dipyrithione, ditalimfos, dithianon, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, etaconazole, ethirimol, ethoxyquin, ethyl (Z)-N-benzyl-N-([methyl(methyl- thioethylideneamino-oxycarbonyl)amino]thio)-β-alaninate, etridiazole, famoxadone, fenaminosulph, fenapanil, fenarimol, fenbuconazole, fenfuram, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone, fluazinam, fludioxonil, fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fuberidazole, furalaxyl, furametpyr, furconazole-cis, guazatine, hexaconazole, hydroxy isoxazole, hymexazole, imazalil, imibenconazole, iminoctadine albesilate, ipconazole, iprobenfos, iprodione, isopropanyl butyl carbamate, isoprothiolane, kasugamycin, kresoxim-methyl, KTU3616, man- cozeb, maneb, mepanipyrim, mepronil, metalaxyl, metconazole, methfuroxam, metiram, metiram-zinc, metsulfovax, MON41100, myclobutanil, NTN0301, neoasozin, nickel dimethyldithiocarbamate, nitrothal-isopropyl, nuarimol, ofurace, organomercury compounds, oxadixyl, oxolinic acid, oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-Al, phosphorus acids, phthalide, polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb, propamocarb hydrochloride, propiconazole, propineb, propionic acid, prothiocarb, pyracarbolid, pyrazophos, pyrifenox, pyrimethanil, pyroquilon, pyroxyfur, pyrrolnitrin, quaternary ammonium compounds, quinconazole, quinomethionate, quinoxyfen, quintozene, rabenazole, sodium pentachlorophenate, spiroxamine, streptomycin, sulphur, tebuconazole, techlofthalam, tecnazene, tetraconazole, thiabendazole, thicyofen, thifluzamide, 2-(thiocyanomethylthio)benzothiazole, thiophanatemethyl, thiram, timibenconazole, tolclofos-methyl, tolylfluanid, triacetate salt of l,r-iminodi(octamethylene)diguanidine, triadimefon, triadimenol, triazbutyl, triazoxide, tricyclazole, tridemorph, triforine, triflumizole, triticonazole, validamycin A, vapam, vinclozolin, XRD-563, zineb and ziram. The compounds of general formula (I) can be mixed with soil, peat or other rooting media for the protection of plants against seed-borne, soil-borne or foliar fungal diseases. The following Examples illustrate the invention. Throughout the Examples, the term
'ether' refers to diethyl ether, magnesium sulphate was used to dry solutions except where otherwise indicated, and solutions were concentrated under reduced pressure. All reactions were performed under an atmosphere of nitrogen and solvents were dried before use, where appropriate. Unless otherwise stated, chromatography was performed on a column of silica gel as the stationary phase. The following abbreviations are used throughout:
ppm = parts per million nmr = nuclear magnetic resonance t = triplet mp = melting point s = singlet m = multiplet d = doublet br = broad EXAMPLE 1 This Example illustrates the preparation of 5-methyl-5-[4-(2-r-butyl-5-pyrimidinyl- methoxy)phenyl]-3-phenylamino-l,3-oxazolidine-2,4-dione (Compound 1 of Table 1 1).
Preparation of 4-bromo- 1 -(f-butyldimethylsiloxy)benzene
Imidazole (70.7 g, 1.04 mol) was added in one portion to a stirred solution of t~ butyldimethylsilyl chloride (157 g, 1.04 mol) in dimethylformamide (600 ml). To this was added 4-bromophenol (180 g, 1.04 mol) in two portions. The reaction mixture was stirred at ambient temperature for 3 hours and then allowed to stand for 17 hours. The mixture was poured into water (1000 ml) and extracted with ether. The combined organic extracts were washed with brine, dried and evaporated to provide the title compound (294 g, 98%) as an oil.
Η nmr (CDC13) δ 0.19 (6H, s), 0.97 (9H, s), 6.71 (2H, d), 7.32 (2H, d) ppm.
Preparation of 2-(4-f-butyldimethylsiloxyphenyl)-2-hydroxypropionic acid
Magnesium metal (9 g, 0.38 mol) was heated under nitrogen for 5 minutes. Iodine (5 crystals) was added, followed by dry tetrahydrofuran (50 ml). 4-Bromo-l-(f-butyldimethyl- siloxy)benzene (1 g) was added and the mixture warmed for 10 minutes. After the yellow colour was discharged the mixture was heated to reflux and a solution of 4-bromo- l-(t- butyldimethylsiloxy)benzene (97 g, 0.34 mol) in dry tetrahydrofuran (500 ml) added over 1 hour. Once the addition was complete the mixture was heated at reflux for 5 hours and then cooled to 5 °C. Sodium pyruvate (41.2 g, 0.37 mol) was added in one portion and the mixture allowed to warm to room temperature and stirred for 1 hour. The mixture was allowed to stand for 17 hours, then cooled to 5 °C and sodium pyruvate (30 g, 0.27 mol) added. Stirring was continued at 5 °C for 1 hour, then at ambient temperature for 1 hour. Water (500 ml) was added, followed by concentrated hydrochloric acid (60 ml). The phases were separated and the aqueous extracted with ethyl acetate. The combined organic phases were washed with water and brine, dried and evaporated to yield the title compound (70 g). 'H nmr (CDC13) δ 0.20 (6H, s), 0.99 (9H, s), 1.81 (3H, s), 6.81 (2H, d), 7.42
(2H, d) ppm.
Preparation of ethyl 2-(4-r-butyldimethylsiloxyphenyl)-2-hydroxypropionate
A solution of 2-(4-r-butyldimethylsiloxyphenyl)-2-hydroxypropionic acid (70 g, 0.24 mol), di/søpropylethylamine (46 g, 0.35 mol) and ethyl iodide (55 g, 0.35 mol) in dry dimethylformamide (300 ml) was stirred at ambient temperature for 5 hours. The mixture was poured into water (1000 ml) and extracted with ether. The organic extracts were washed with dilute hydrochloric acid, brine and water, dried and evaporated. The crude product was purified by flash vacuum chromatography to yield the title compound (33 g, 38% from 4- bromo-l-(t-butyldimethylsiloxy)benzene) as an oil.
Η nmr (CDCI3) δ 0.11 (6H, s), 0.88 (9H, m), 1.18 (3H, t), 1.67 (3H, s), 3.68 (IH, s), 4.1 1 (2H, m), 6.70 (2H, d), 7.30 (2H, d) ppm.
Preparation of ethyl 2-hydroxy-2-(4-hydroxyphenyl)propionate
A solution of tetrabutylammonium fluoride (IM in tetrahydrofuran; 446 ml, 0.446 mol) was added to a stirred solution of ethyl 2-(4-t-butyldimethylsiloxyphenyl)-2- hydroxypropionate (135 g, 0.416 mol) in dry tetrahydrofuran (300 ml) at 5 °C. The solution was allowed to warm slowly to ambient temperature and stirred for 1 hour, then allowed to stand for 17 hours. The mixture was reduced in volume and then poured into water (600 ml). The resulting mixture was extracted with ethyl acetate and the combined organic extracts washed with water and brine, dried and evaporated to provide a red gum, which was purified by flash vacuum chromatography to yield the title compound as an orange gum (77 g, 88%).
'H nmr (CDC13) δ 1.25 (3H, t), 1.76 (3H, s), 3.87 (IH, s), 4.22 (2H, m), 5.70
(IH, br s), 6.79 (2H, d), 7.40 (2H, d) ppm.
Preparation of 2-r-butyl-5-(hydroxymethyl)pyrimidine Sodium borohydride (176 mg, 4.6 mmol) was added in one portion to a stirred solution of 2-?-butylpyrimidine-5-aldehyde (2.28 g, 13.9 mmol) in dry ethanol (15 ml) at 5 °C under nitrogen. After stirring for 1 hour the mixture was poured into water and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried and evaporated to provide the title compound (2.23 g, 97%) as an orange oil.
Η nmr(CDCl3) δ 1.40 (9H, s), 2.52 (IH, s), 4.71 (2H, s), 8.69 (2H, s) ppm.
Preparation of 2-r-butyl-5-(chloromethyl)pyrimidine
2-t-Butyl-5-(hydroxymethyl)pyrimidine (720 mg, 4.3 mmol) was cooled to 0 °C and phosphorus oxychloride (3 ml) added. The mixture was heated at 100 °C for 1 hour, then cooled and poured onto ice. The resulting mixture was extracted with ether, and the combined organic extracts washed with water, dried and evaporated to provide the title compound (800 mg, 100%) as an oil.
lH nmr (CDC13) δ 1.41 (9H, s), 4.57 (2H, s), 8.71 (2H, s) ppm.
Preparation of ethyl 2-[4-(2-t-butyl-5-pyrimidinylmethoxy)phenyl]-2-hydroxypropionate
A mixture of ethyl 2-hydroxy-2-(4-hydroxyphenyl)propionate (909 mg, 4.3 mmol), 2- t-butyl-5-(chloromethyI)pyrimidine (800 mg, 4.3 mmol), potassium carbonate (598 mg, 4.3 mmol) and dry dimethylformamide (15 ml) was stirred under nitrogen at 70 °C for 5 hours.
The mixture was cooled to ambient temperature, poured into water and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried and evaporated. The crude product was purified by flash chromatography to yield the title compound as an oil
(1.33 g, 86%).
]H nmr(CDCl3) δ 1.28 (3H, t), 1.42 (9H, s), 1.77 (3H, s), 3.80 (IH, s), 4.22 (2H, m), 5.03 (2H, s), 6.96 (2H, d), 7.50 (2H, d), 8.77 (2H, s) ppm. Preparation of 5-[4-(2-r-butyl-5-pyrimidinylmethoxy)phenyl]-5-methyl-3-phenylamino-l,3- oxazolidine-2,4-dione
A solution of ethyl 2-[4-(2-r-butyl-5-pyrimidinylmethoxy)phenyi]-2- hydroxypropionate (1.2 g, 3.4 mmol) and 1,1 '-carbonyldiimidazole (970 mg, 5.9 mmol) in dry dichloromethane (15 ml) was heated at reflux for 5 hours, then cooled to ambient temperature and poured into water. The mixture was extracted with dichloromethane and the combined organic extracts washed with water, dried and evaporated.
The residue was dissolved in dry dichloromethane (10 ml), and phenylhydrazine (424 mg, 3.9 mmol) and acetic acid (0.3 ml, 4.9 mmol) added. The resulting solution was stirred at ambient temperature for 17 hours and then poured into water. The mixture was extracted with dichloromethane, and the combined organic extracts washed with water, dried and evaporated. The crude product was purified by flash chromatography, then washed with hexane to provide the title compound as a powder (453 mg, 31 %).
m.p. 158 - 161 °C.
EXAMPLE 2 This Example illustrates the preparation of 5-[4-(4-methoxy-6-methyl-2- pyrimidinylmethoxy)phenyl]-5-methyl-3-phenylamino- 1 ,3-oxazolidine-2,4-dione (Compound 1 of Table 2)
Preparation of ethyl 2-[4-(4-methoxy-6-methyl-2-pyrimidinylmethoxy)phenyl]-2- hydroxypropionate
Dimethyl sulphate (0.3 ml, 3.15 mmol) was added to a stirred suspension of potassium carbonate (479 mg, 3.5 mmol) and 2-ch]oromethyl-4-hydroxy-6-methylpyrimidine (500 mg, 3.15 mmol) in acetone (20 ml). The mixture was heated at reflux for 4 hours, then cooled to ambient temperature and filtered through Hyflo Super Cel®, the solid being washed with further acetone. The filtrate was evaporated to provide a mixture of 2 -chloromethyl -4- methoxy-6-methylpyrimidine and 2-chloromethyl-l,4-dimethyl-6-oxopyrimidine as an orange oil (556 mg). This mixture (373 mg, 2.16 mmol) and potassium iodide (catalytic) were added to a stirred suspension of ethyl 2-hydroxy-2-(4-hydroxyphenyl)propionate (prepared as described in Example 1) (413 mg, 2.0 mmol) and potassium carbonate (326 mg, 2.36 mmol) in acetone (10 ml). The resulting mixture was heated at reflux for 65 hours, then cooled to ambient temperature and filtered through Hyflo Super Cel®, the solid being washed with further acetone. The filtrate was evaporated to provide an orange oil, which was purified by flash chromatography to provide the title compound (145 mg) and ethyl 2-[4-(l,4-dimethyl-6-oxo- 2-pyrimidinylmethoxy)phenyl]-2-hydroxypropionate (428 mg).
Preparation of 5-[4-(4-methoxy-6-methyl-2-pyrimidinylmethoxy)phenyl]-5-methyl-3- phenylamino- 1 ,3-oxazolidine-2,4-dione
A solution of ethyl 2-[4-(4-methoxy-6-methyl-2-pyrimidinylmethoxy)phenyl]-2- hydroxypropionate (452 mg, 1.35 mmol) and 1,1 '-carbonyldiimidazole (373 mg, 2.27 mmol) in dry dichloromethane (10 ml) was heated at reflux for 5 hours. Additional 1,1'- carbonyldiimidazole (219 mg, 1.35 mmol) was added and heating continued. Once reaction was complete (as judged by gas chromatography) the mixture was cooled to ambient temperature and poured into water. The mixture was extracted with dichloromethane and the combined organic extracts washed with water and brine, dried and evaporated to leave a yellow oil (607 mg).
The residue was dissolved in dry dichloromethane (10 ml), and phenylhydrazine (179 mg, 1.7 mmol) and acetic acid (0.12 ml, 2.0 mmol) added. The resulting solution was stirred at . ambient temperature for 24 hours, then additional phenyl hydrazine (90 mg, 0.8 mmol) added, the mixture heated at reflux for 12 hours, cooled to ambient temperature and then poured into water. The mixture was extracted with dichloromethane, and the combined organic extracts washed with dilute hydrochloric acid, aqueous sodium bicarbonate and brine, dried and evaporated. The crude product was purified by flash chromatography to provide the title compound as a powder (243 mg).
m.p. 72 - 74 °C. EXAMPLE 3
This Example illustrates the preparation of 5-[4-( l ,4-dimethyl-6-oxo-2-pyrimidinylmethoxy)- phenyl]-5-methyl-3-phenylamino-l,3-oxazolidine-2,4-dione (Compound 1 of Table 6)
Preparation of 5-[4-( 1 ,4-dimethyl-6-oxo-2-pyrimidinylmethoxy)phenyl]-5-methyl-3- phenylamino- 1 ,3-oxazolidine-2,4-dione
A solution of ethyl 2-[4-( 1 ,4-dimethyl-6-oxo-2-pyrimidinylmethoxy)phenyl]-2- hydroxypropionate (prepared as described in Example 2) (300 mg, 0.87 mmol) and 1,1 '- carbonyldiimidazole (281 mg, 1.73 mmol) in dry dichloromethane (30 ml) was heated at reflux until reaction was complete (7 days). Dichloromethane was added and the solution washed with water. The aqueous phase was extracted with dichloromethane and the combined organic phases washed with water and brine, dried and evaporated to leave a colourless gum (460 mg).
The residue was dissolved in dry dichloromethane (25 ml), and phenylhydrazine (168 mg, 1.55 mmol) and acetic acid (0.09 ml, 1.5 mmol) added. The resulting solution was heated at reflux for 17 hours, cooled to ambient temperature and then poured into water. The mixture was extracted with dichloromethane, and the combined organic extracts washed with water and brine, dried and evaporated. The crude product was purified by flash chromatography to provide the title compound as a powder (250 mg).
m.p. 163 - 164.5 °C.
EXAMPLE 4
This Example illustrates the preparation of 5-methyl-5-[4-(2-methyl-5- pyrimidinylmethoxy)phenyl]-3-phenylamino-l,3-oxazolidine-2,4-dione (Compound 1 of Table 10)
Preparation of 5-chloromethyl-2-methylpyrimidine
A solution of 2,5-dimethylpyrimidine (4.2 g, 39 mmol) and benzoyl peroxide (159 mg, 0.66 mmol) in carbon tetrachloride (70 ml) was heated at reflux for 48 hours, during which time N- chlorosuccinimide (10.6 g, 82 mmol) was added in several portions. The mixture was then cooled to ambient temperature, filtered and the filtrate evaporated. The crude product was purified by flash chromatography to provide a 1 : 1 mixture of the title compound and 2- chloromethyl-5-methy Ipyrimidine (630 mg).
Preparation of ethyl 2-[4-(2-methyl-5-pyrimidinylmethoxy)phenyl]-2-hydroxypropionate
A suspension of the above mixture (630 mg, 4.42 mmol), ethyl 2-hydroxy-2-(4- hydroxyphenyl)propionate (prepared as described in Example 1) (930 mg, 4.42 mmol), potassium carbonate (732 mg, 5.3 mmol) and potassium iodide (catalytic) in acetone (50 ml was heated at reflux for 6 hours, then cooled to ambient temperature and filtered through Hyflo Super Cel®, the solid being washed with further acetone. The filtrate was evaporated to provide an oil, which was purified by flash chromatography to provide the title compound (206 mg).
Preparation of 5-methyl-5-[4-(2-methyl-5-pyrimidinylmethoxy)phenyl]-3-phenylamino- 1 ,3- oxazolidine-2,4-dione
A solution of ethyl 2-[4-(2-methyl-5-pyrimidinylmethoxy)phenyl]-2-hydroxypropionate (200 mg, 0.63 mmol) and 1,1 '-carbonyldiimidazole (205 mg, 1.27 mmol) in dichloromethane (10 ml) was heated at reflux for 21 hours. Additional 1,1' -carbonyldiimidazole (205 mg, 1.27 mmol) was added and heating continued for a further 17 hours. The mixture was then cooled to ambient temperature and poured into water. The mixture was extracted with dichloromethane and the combined organic extracts washed with water and brine, dried and evaporated to leave an orange gum (263 mg).
The residue was dissolved in dry dichloromethane ( 10 ml), and phenylhydrazine (82 mg, 0.76 mmol) and acetic acid (0.055 ml, 0.95 mmol) added. The resulting solution was heated at reflux for 27 hours, then additional phenyl hydrazine (68 mg, 0.63 mmol) added, the mixture heated at reflux for a further 17 hours, cooled to ambient temperature and then poured into water. The mixture was extracted with dichloromethane, and the combined organic extracts washed water and brine, dried and evaporated. The crude product was purified by flash chromatography to provide the title compound as a solid (36 mg).
Η nmr(CDCl3) δ 1.97 (3H, s), 2.87 (3H, s), 5.06 (2H, s), 6.31 ( IH, s), 6.72
(2H, d), 7.01 (3H, m), 7.23 (2H, t), 7.53 (2H, d), 8.72 (2H, s) ppm.
EXAMPLE 5
This Example illustrates the preparation of 5-methyl-5-[4-(2-trifluoromethyl-5- pyrimidinylmethoxy)phenyl]-3-phenylamino-l,3-oxazolidine-2,4-dione (Compound 1 of Table 12)
Preparation of 2-methyl-5-trifluoromethylpyrimidine
Sodium metal (1.03 g, 44.6 mmol) was added to dry ethanol (70 ml). Once the sodium had dissolved trifluoroacetamidine (5.0 g, 44.6 mmol), followed by 3-ethoxymethacrolein (5.28 ml, 44.6 mmol), were added to the stirred solution. The mixture was heated at reflux for 90 minutes, then cooled to ambient temperature and evaporated. The solid residue was dissolved in dichloromethane, and the solution washed with water and brine, dried and evaporated to provide the title compound as a yellow solid.
m.p. 40 - 42 °C.
Preparation of 5-bromomethyl-2-trifluoromethy Ipyrimidine Benzoyl peroxide (40 mg, 0.17 mmol) was added to a solution of 2-methyl-5- trifluoromethylpyrimidine (1.0 g, 6.2 mmol) and N-bromosuccinimide (1.1 g, 6.2 mmol) in carbon tetrachloride (25 ml) at reflux. The mixture was heated at reflux for 8 hours, then cooled to ambient temperature, filtered and evaporated. The residue was purified by flash chromatography to provide the title compound (443 mg).
Using the method described in Example 4 this material was converted into 5-methyl-5-[4-(2- trifluoromethyl-5-pyrimidinylmethoxy)phenyl]-3-phenylamino-l,3-oxazolidine-2,4-dione.
m.p. 138 - 140 °C.
EXAMPLE 6
This Example illustrates the preparation of 5-[4-(4-allyloxy-6-methyl-2-pyrimidinylmethoxy)- phenyl]-5-methyl-3-phenylamino-l,3-oxazolidine-2,4-dione (Compound 1 of Table 3)
Preparation of 4-allyloxy-2-chloromethyl-6-methylpyrimidine
A mixture of 2-chloromethyM-hydroxy-6-methylpyrimidine ( 1.0 g, 6.31 mmol), allyl bromide (0.66 ml, 7.62 mmol) and silver carbonate (2.1 g, 7.61 mmol) in acetone (30 ml) was heated at reflux for 6 hours, then cooled to ambient temperature and filtered through Hyflo Super Cel®, the solid being washed with further acetone. The filtrate was evaporated to provide the title compound as a yellow oil (373 mg).
Preparation of ethyl 2-[4-(4-allyloxy-6-methyl-2-pyrimidinylmethoxy)phenyl]-2- hydroxypropionate
A mixture of 4-allyloxy-2-chloromethyl-6-methylpyrimidine (393 mg, 1.98 mmol), ethyl 2- hydroxy-2-(4-hydroxyphenyl)propionate (prepared as described in Example 1) (416 mg, 1.98 mmol), potassium carbonate (410 mg, 2.97 mmol) and potassium iodide (catalytic) in acetone (10 ml) was heated at reflux for 1 1 hours. The mixture was then cooled to ambient temperature and filtered through Hyflo Super Cel®, the solid being washed with further acetone. The filtrate was evaporated to provide a yellow oil, which was purified by flash chromatography to provide the title compound (560 mg).
Preparation of 5-[4-(4-allyloxy-6-methyl-2-pyrimidinylmethoxy)phenyl]-5-methyl-3- phenylamino- 1 ,3-oxazolidine-2,4-dione
A solution of ethyl 2-[4-(4-allyloxy-6-methyl-2-pyrimidinylmethoxy)phenyl]-2- hydroxypropionate (531 mg, 1.5 mmol) and 1,1 '-carbonyldiimidazole (483 mg, 3.0 mmol) in dry dichloromethane (20 ml) was heated at reflux for 17 hours. The mixture was then cooled to ambient temperature and poured into water. The mixture was extracted with dichloromethane and the combined organic extracts washed with water and brine, dried and evaporated to leave a yellow oil (662 mg).
The residue was dissolved in dry dichloromethane (20 ml), and phenylhydrazine (169 mg, 1.6 mmol) and acetic acid (0.14 ml, 2.3 mmol) added. The resulting solution was heated at reflux for 80 hours, cooled to ambient temperature and then poured into water. The mixture was extracted with dichloromethane, and the combined organic extracts washed with water and brine, dried and evaporated. The crude product was purified by flash chromatography to provide the title compound as an orange gum (229 mg).
Η nmr (CDC13) δ 1.97 (3H, s), 2.46 (3H, s), 4.82 (2H, dd), 5.25 (2H, s), 5.2 -
5.4 (2H, m), 5.9 - 6.0 (IH, m), 6.04 (IH, br s), 6.50 (IH, s), 6.73 (2H, dd), 6.95 (3H, m), 7.24 (2H, m), 7.47 (2H, m) ppm.
EXAMPLE 7
This Example illustrates the preparation of 5-[4-(2-pyrazinylrnethoxy)phenyl]-5-methyl-3- phenylamino-l,3-oxazolidine-2,4-dione (Compound 1 of Table 16)
Preparation of methyl pyrazine-2-carboxylate
Concentrated sulphuric acid (8 ml) was carefully added to a solution of pyrazine-2-carboxylic acid (12.4 g, 0.1 mol) in methanol (100 ml). The resulting solution was heated at reflux for 5 hours, then cooled to ambient temperature and evaporated. The residue was added to water and the mixture extracted with ethyl acetate. The combined organic extracts were washed with water and brine, dried and evaporated to provide the title compound as a cream solid.
Preparation of 2-hydroxymethylpyrazine
Sodium borohydride (6.85 g, 0.18 mol) was added portionwise to a stirred solution of methyl pyrazine-2-carboxylate (5.0 g, 36 mmol) in water (100 ml). The mixture was then stirred at ambient temperature for 9 hours. Ethanol (10 ml) was added, followed by excess potassium carbonate, and the mixture extracted with ethyl acetate. The combined organic extracts were washed with water and brine, dried and evaporated to provide the title compound as a brown oil.
Preparation of ethyl 2-[4-(2-pyrazinylmethoxy)phenyl]-2-hydroxypropionate
Methanesulphonyl chloride (677 mg, 5.91 mmol) was to a stirred solution of 2- hydroxymethylpyrazine (500 mg, 4.5 mmol) and triethylamine (1.3 ml, 9.1 mmol) in dry dichloromethane (10 ml) at 0 °C. The solution was stirred at ambient temperature for 5 hours, then poured into water and extracted with dichloromethane. The combined organic extracts were washed with water and brine, dried and evaporated to provide a dark brown oil.
Potassium carbonate (652 mg, 4.7 mmol) and potassium iodide (catalytic) were added to a solution of the above prepared mesylate (405 mg, 3.15 mmol) and ethyl 2-hydroxy-2-(4- hydroxyphenyl)propionate (prepared as described in Example 1) (662 mg, 3.15 mmol) in dry dimethylformamide (10 ml). The mixture was heated at reflux for 6 hours, then cooled to ambient temperature, poured into water and extracted with diethyl ether. The combined organic extracts were washed with water and brine, dried and evaporated to provide a yellow oil, which was purified by flash chromatography to provide the title compound (695 mg).
Preparation of 5-[4-(2-pyrazinylmethoxy)phenyl]-5-methyl-3-phenylamino- 1 ,3-oxazolidine- 2,4-dione A solution of ethyl 2-[4-(2-pyrazinylmethoxy)phenyl]-2-hydroxypropionate (695 mg, 2.3 mmol) and 1,1 '-carbonyldiimidazole (746 mg, 4.6 mmol) in dry dichloromethane (20 ml) was heated at reflux for 17 hours. The mixture was then cooled to ambient temperature and poured into water. The mixture was extracted with dichloromethane and the combined organic extracts washed with water and brine, dried and evaporated to leave a yellow oil (959 mg).
The residue was dissolved in dry dichloromethane (20 ml), and phenylhydrazine (289 mg, 2.7 mmol) and acetic acid (0.24 ml, 4.0 mmol) added. The resulting solution was heated at reflux for 80 hours, cooled to ambient temperature and then poured into water. The mixture was extracted with dichloromethane, and the combined organic extracts washed with water and brine, dried and evaporated. The crude product was triturated with hot diethyl ether to provide the title compound as a cream powder (465 mg).
m.p. 146 - 148 °C.
EXAMPLE 8 The compounds were tested against a variety of foliar fungal diseases of plants. The technique employed was as follows. The plants were grown in John Innes Potting Compost (No 1 or 2) in 4 cm diameter minipots. The test compounds were formulated either by bead milling with aqueous Dispersol T or as a solution in acetone or acetone/ethanol which was diluted to the required concentration immediately before use. The formulations (100 ppm active ingredient) were sprayed on to the foliage of the plants to a maximum retention. Tween 20 was added to give a final concentration of 0.05% when the sprays were applied to cereals.
The compounds were applied to the foliage (by spraying) one or two days before the plant was inoculated with the disease. Foliar pathogens were applied by spray as zoosporangial suspensions onto the leaves of test plants. After inoculation, the plants were put into an appropriate environment to allow infection to proceed and then incubated until the disease was ready for assessment. The period between inoculation and assessment varied from four to fourteen days according to the disease and environment. The disease level present (i.e. leaf area covered by actively sporulating disease) on each of the treated plants was recorded using the following assessment scale:
0 = 0% disease present 20 = 10.1-20% disease present 1 = 0.1-1% disease present 30 = 20.1-30% disease present
3 = 1.1-3% disease present 60 = 30.1-60% disease present
5 = 3.1-5% disease present 90 = 60.1-100% disease present
10 = 5.1-10% disease present
Each assessment was then expressed as a percentage of the level of disease present on the untreated control plants. This calculated value is referred to as a POCO (Percentage of Control) value. An example of a typical calculation is as follows:
Disease level on untreated control = 90 Disease level on treated plant = 30
POCO = disease level on treated plant x 100 = 30 x 100 = 33.3 disease level on untreated control 90
This calculated POCO value is then rounded to the nearest of the values in the 9-point assessment scale shown above. In this particular example, the POCO value would be rounded to 30. If the calculated POCO falls exactly mid-way between two of the points, it is rounded to the lower of the two values. The results are shown in Table 9.
TABLE 9
Figure imgf000034_0001
- No confirmed result
Key to Diseases LEPTNO Septoria nodorum PLASVI Plasmopara viticola PUCCRT Puccinia recondita PHYTIN Phytophthora infestans ERYSGT Erysiphe graminis i.sp.tritici lycopersici

Claims

A compound having the general formula (I):
Figure imgf000035_0001
wherein R' is a C-linked 6-membered heteroaromatic ring containing 2 or 3 nitrogen atoms and which is optionally N- or C-substituted with one or more of halo, hydroxy, oxo, CM alkyl, C3.6 cycloalkyl, halo(d.6)alkyl, CM alkoxy(Ci.6)alkyl, aryl(C|.6)alkyl, C|.6 alkoxy, halo(C|.6)alkoxy, C2-4 alkenyloxy, C1.6 alkylthio, Cι-6 alkylcarbonyl, C!-6 alkylcarbonylamino, Q.6 alkoxycarbonyl, arylcarbonyl, aryl, aryloxy, or heteroaryl, the aryl and heteroaryl substituents themselves being optionally substituted with one or more of halo, Ci-β alkyl, halo(Cι-6)alkyl, Cι.6 alkoxy, halo(Cι_6)alkoxy, CM alkoxy(C|. 6)alkyl, nitro, amino, mono- or di(Cι.4)alkylamino, cyano, Cι-6 alkoxycarbonyl or Cι-6 alkylcarbonyl, and R2 is phenyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, triazolyl, thiadiazolyl, oxadiazolyl or tetrazolyl, any of which is optionally substituted with one or more of halo, Cι-6 alkyl, halo(Cι.6)alkyl, Cι-6 alkoxy, halo(C|. 6)alkoxy, Cι_6 alkylthio, nitro, cyano, thiocyanato, CM alkylsulphonyl, halo(Cι. 4)alkylsulphonyl, aminosulphonyl or Ci-6 alkoxycarbonyl or, two adjacent substituents join to form with the carbon atoms to which they are attached a fused benzene ring optionally substituted with halo, CM alkyl or CM alkoxy.
A compound according to claim 1 in which the 6-membered heteroaromatic ring R1 is selected from 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl,
2-pyrazinyl, 3-pyridazinyl or 2-( 1,3,5-triazinyl) optionally N- or C-substituted with one or more of the R1 substituents listed in claim 1. 3. A compound according to claim 1 in which R1 is 2-pyrimidinyl optionally substituted with hydroxy, oxo, C,.4 alkyl, C3.6 cycloalkyl, halo(CM)alkyl, CM alkoxy, halo(C,. 4)alkoxy or C2-4 alkenyloxy; 4-pyrimidinyl optionally substituted in the 2-position with CM alkyl, C3.6 cycloalkyl, halo(Cι-4)alkyl, C)-4 alkoxy, halo(C,.4)alkoxy, CM alkylthio, aryl, aryl(Cι-4)alkyl or heteroaryl and in the 5- and 6-positions with hydroxy, C,.4 alkyl,
C3.6 cycloalkyl, halo(Cι.4)alkyl, CM alkoxy or halo(Cι_4)alkoxy; 5-pyrimidinyl optionally substituted in the 2-position with Cι-4 alkyl, C3.6 cycloalkyl, halo(C).4)alkyl, C]-4 alkoxy, halo(Cι.4)alkoxy, Q.4 alkylthio, aryl or heteroaryl and in the 4- and 6- positions with CM alkyl, C3.6 cycloalkyl, halo(Ct.4)alkyl, CM alkoxy or halo(C|. 4)alkoxy; 1,
3,5-triazinyl optionally substituted with C M alkyl, halo(C|.4)alkyl, Cl-4 alkoxy or aryl; 3-( 1 ,2,4-triazinyl) optionally substituted with CM alkyl, halo(C|-4)alkyl, Cι.4 alkoxy or aryl; 5-(l,2,4-triazinyl) optionally substituted with CM alkyl, halo(C|. 4)alkyl, Cι-4 alkoxy or aryl; 6-(l,2,4-triazinyl) optionally substituted with CM alkyl, halo(Cι.4)alkyl, C).4 alkoxy or aryl; 3-pyridazinyl optionally substituted with C|.4 alkyl, halo (CM)alkyl, C)-4 alkoxy or aryl; 4-pyridazinyl optionally substituted with CM alkyl, halo(Cι.4)alkyl, CM alkoxy or aryl; or 2-pyrazinyl optionally substituted with CM alkyl, halo(Cι.4)alkyl, CM alkoxy or aryl.
4. A compound according to any one of the preceding claims in which R2 is unsubstituted phenyl.
5. A compound according to any one of claims 1 to 3 in which R2 is phenyl substituted with a bromine or iodine atom, with 1 to 5 chlorine or fluorine atoms, with 4 chlorine or fluorine atoms and a methyl or trifluoromethyl group or with 1 to 3 substituents selected from halo, Cι-4 alkyl, halo(C|.4)alkyl, C|.4 alkoxy, halo(Cι.4)alkoxy, CM alkylthio, nitro, cyano, thiocyanato, CU4 alkylsulphonyl, halo(Cι.4)alkylsulphonyl, aminosulphonyl or CM alkoxycarbonyl, or naphthyl.
6. A compound according to any one of claims 1 to 3 in which R2 is 2-, 3- or 4-pyridyl, 2-, 4- or 5-pyrimidinyl, 3-pyridazinyl, 3-thienyl, 3- or 5-pyrazolyl, 2-thiazolyl, 3-( 1,2,4- triazolyl), 5-(l,2,3-thiadiazolyl) or 5-tetrazolyl, any of which is optionally substituted with 1 to 3 substituents selected from halo, CM alkyl, haio(CM)alkyl, CM alkoxy, halo(CM)alkoxy, nitro, cyano, phenyl, CM alkylsulphonyl or CM alkoxycarbonyl or, in the case of pyridyl, with 4 fluorine or chlorine atoms.
7. A compound according to any one of claims 1 to 3 in which R2 is 2-, 3- or 4- quinolinyl, 4-quinazolinyl, 1-phthalazinyl, 2-quinoxalinyl, 3-(l,2,4-benzotriazinyl), 2- benzoxazolyl or 2-benzothiazolyl, any of which is optionally substituted in its fused benzene ring with halo, CM alkyl, C1-4 alkoxy or nitro and in its heterocyclic ring with halo, CM alkyl, halo(CM)alkyl, CM alkoxy, halo(C|.4)alkoxy, nitro, cyano, CM alkylsulphonyl or C1-4 alkoxycarbonyl.
8. A process for preparing a compound according to claim 1 which comprises the steps:
(i) reacting a compound of formula (II):
Figure imgf000037_0001
in which R1 has the meaning given in claim 1 and R is CM alkyl, with a carbonylating agent in a water-immiscible solvent at an elevated temperature, and (ii) reacting the product obtained from step (i) with a hydrazine of formula R2 NHNH2 in which R2 has the meaning given in claim 1, in a water immiscible solvent in the presence of an acid catalyst.
9. A fungicidal composition comprising a fungicidally effective amount of a compound according to claim 1 and a fungicidally acceptable carrier or diluent therefor.
10. A method of combating fungi which comprises applying to plants, to the seeds of plants or to the locus of the plants or seeds, a compound according to claim 1 or a composition according to claim 9.
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WO1991015480A1 (en) * 1990-04-10 1991-10-17 E.I. Du Pont De Nemours And Company Fungicidal oxazolidinones
WO1991019703A2 (en) * 1990-06-11 1991-12-26 E.I. Du Pont De Nemours And Company Fungicidal iminooxazolidinones
EP0503798A1 (en) * 1991-03-15 1992-09-16 E.I. Du Pont De Nemours And Company Fungicidal 4-thixooxazolidin-2-ones and 4-iminooxazolindin-2-ones
WO1993018016A1 (en) * 1992-03-11 1993-09-16 E.I. Du Pont De Nemours And Company Fungicidal oxazolidinones
WO1993022299A1 (en) * 1992-04-24 1993-11-11 E.I. Du Pont De Nemours And Company Fungicidal oxazolidinones
WO1994011359A1 (en) * 1992-11-13 1994-05-26 E.I. Du Pont De Nemours And Company Processes for preparing 2,4-oxazolidinediones
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WO1991015480A1 (en) * 1990-04-10 1991-10-17 E.I. Du Pont De Nemours And Company Fungicidal oxazolidinones
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