WO1997038997A1 - Substituted oxazolidinediones and their use as fungicides - Google Patents

Substituted oxazolidinediones and their use as fungicides Download PDF

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Publication number
WO1997038997A1
WO1997038997A1 PCT/GB1997/000823 GB9700823W WO9738997A1 WO 1997038997 A1 WO1997038997 A1 WO 1997038997A1 GB 9700823 W GB9700823 W GB 9700823W WO 9738997 A1 WO9738997 A1 WO 9738997A1
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Prior art keywords
alkyl
halo
aryl
alkoxy
optionally substituted
Prior art date
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PCT/GB1997/000823
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French (fr)
Inventor
Margaret Jean Huggett
William Guy Whittingham
Kirsteen Isobel Buchanan
Paul John De Fraine
Lynda Bywaters
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Zeneca Limited
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Application filed by Zeneca Limited filed Critical Zeneca Limited
Priority to AU20390/97A priority Critical patent/AU2039097A/en
Publication of WO1997038997A1 publication Critical patent/WO1997038997A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links

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 2 is phenyl, pyridyl, pyrimidinyi, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl.
  • Halo includes fluoro. chloro, bromo and i ⁇ do. Most commonh it is fluoro or chloro Haloalkyl is typically t ⁇ fluoromethyl and haloalkoxy is typicalh t ⁇ fluoromethoxy Aryl is usually phenyl but also includes naphthyl
  • Heteroaryl includes the residues of 6-membered heteroaromatic rings containing irom 1 to 3 N atoms, eg py ⁇ dyl. pyrimidinyi, pyrazinyl, pyridazinyl or 1.3.5-tridz ⁇ nyl. 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. isothiazolyi. isoxazolyl, pyrazolyl, imidazolyl, thiadiazolvi, oxadiazolvi or t ⁇ azolyl.
  • heteroaryl is py ⁇ dyl, thienyl, furyl, pyrrolyl. isoxazolyl or isothiazolyi
  • the 5-membered heterocyclic ring R 1 is suitably selected from thiazolyl, oxazolyl, isothiazolyi, isoxazolyl, pyrazolyl. imidazolyl, 1,2,3-, 1.2,4-, 1,2.5- and 1.3.4-th ad ⁇ azolyl, 1,2,4-, 1.2,5- and 1,3,4-oxad ⁇ azolyl, 1,2,3- and 1,2,4-t ⁇ azolyl and tetrazolyl Typically R 1 is 2-th ⁇ azolyl, 4-th ⁇ azolyl, 5-th ⁇ azolyl, 4-oxazolyl, 3- ⁇ soxazolyl, 4- ⁇ soxazolyl.
  • R 1 IS 2-th ⁇ azolyl optionally substituted with halo, C, 4 alkyl or halo(C, 4 )alkyl; 4-th ⁇ azolyl optionally substituted in the 2-pos ⁇ t ⁇ on with C, alkyl, halo(C ⁇ - 4 )alkyl, Ci 4 alkoxy, halo(C, )alkoxy, C, 4 alkylcarbonylarmno, aryl or heteroaryl and in the 5-pos ⁇ t ⁇ on with halo, C ⁇ 4 alkyl or halo(C, )alkyl.
  • 5-th ⁇ azoiyl optionally substituted in the 2-pos ⁇ t ⁇ on with halo, C ⁇ 4 alkyl, halo(C, 4)alkyl, C ⁇ alkoxy.
  • 3-pyrazolyl optionally substituted in the 1 -position with C
  • alkoxycarbonyl or aryl l -( l ,2.4-triazolyl) optionally substituted with C alkyl, halo(C )alkyl or aryl; 3-( l ,2.4-triazolyl) optionally substituted in the 1 -position with C 1 .4 alkyl, halo(C ⁇ . 4 )alkyl or aryl and in the 5-position with C alkyl, halo(C
  • the aryl or heteroaryl substituent of the 5-membered heterocyclic ring R 1 may be any aryl or heteroaryl group defined above and may be optionally substituted with one or more of halo, C alkyl, halo(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, C M alkyl, halo(C ⁇ -4 )alkyl, C M alkoxy, halo(C )alkoxy, C alkylthio, nitro, cyano, thiocyanato, C
  • R 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-tnazolyl), 5-( l ,2,3-thiadiazolyl) or 5-tetrazolyl, any of which is optionally substituted with 1 to 3 substituents selected from halo, C M alkyl, halo(C
  • R 2 is, for example, 2-, 3- or 4-qu ⁇ nol ⁇ nyl, 4-qu ⁇ nazohnyl, 1- phthalazinyl, 2-qumoxal ⁇ nyl, 3-(l,2,4-benzot ⁇ az ⁇ nyl), 2-benzoxazolyl or 2-benzothiazolyl, any of which is optionally substituted in its fused benzene ⁇ ng with halo, C
  • Table 2 comprises 167 compounds of the general formula (I), wherein R 1 is 2-methyl- 4-thiazolyl 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 1 is 2-(5- isoxazolyl)-4-thiazolyl 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 2-chloro- 5-thiazolyi and R 2 has the value listed for the correspondingly numbered compound in Table TABLE 5
  • Table 5 comprises 167 compounds of the general formula (I), wherein R 1 is 2-methyl- 5-(2-nitrophenyl)-4-oxazolyl 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 3,5- dimethyl-4-isoxazolyl 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 1 is 5-methyl-
  • 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 3-phenyl- 5-isoxazolyl and R 2 has the value listed for the correspondingly numbered compound in Table I.
  • Table 9 comprises 167 compounds of the general formula (I), wherein R 1 is 4,5- dichloro-1 -imidazolyl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 10 comprises 167 compounds of the general formula (I), wherein R 1 is 2- imidazolyl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 1 1 comprises 167 compounds of the general formula (I), wherein R 1 is l-iso- propyl-2-imidazolyl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 12 comprises 167 compounds of the general formula (I), wherein R 1 is 1- methyl-4-nitro-2-imidazolyl 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 4- imidazolyl 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 4- methyl-5-imidazoiyl 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 2- methyl-4-imidazolyl 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' is 3,5- dimethyl- 1 -pyrazolyl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 17 comprises 167 compounds of the general formula (I), wherein R 1 is 1- methyl-4-chloro-3-pyrazolyl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 21 comprises 167 compounds of the general formula (I), wherein R 1 is 3.5- dimethyl-4-pyrazolyl and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 22 comprises 167 compounds of the general formula (I), wherein R 1 is 3- methyl-5-pyrazolyl and R : has the value listed for the correspondingly numbered compound in Table 1.
  • Table 23 comprises 167 compounds of the general formula (I), wherein R' is 3-( l ,2,4- oxadiazolyl) and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 24 comprises 167 compounds of the general formula (I), wherein R 1 is 5- phenyl-3-(l ,2,4-oxadiazolyl) and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 25 comprises 167 compounds of the general formula (I), wherein R 1 is 5-(4- trifluoromethylphenyl)-3-(l,2,4-oxadiazolyl) and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 26 comprises 167 compounds of the general formula (I), wherein R 1 is 5-(3,5- dimethyl-4-isoxazolyl)-3-( l,2,4-oxadiazolyl) and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 27 comprises 167 compounds of the general formula (I), wherein R' is 5-chloro- 4-( 1.2,3-thiadiazolyl) and R 2 has the value listed for the correspondingly numbered compound in Table 1.
  • Table 28 comprises 167 compounds of the general formula (I), wherein R 1 is 1- phenyl-4-(l,2,3-triazolyl) 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' has the meaning given above and R is, for example, C M alkyl, suitably ethyl, with a carbonylating agent, suitably 1 , r-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 b ⁇ ne 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'-carbonyldumidazole. are commercially available, as are many hydrazines of formula R 2 NHNH 2 Hydrazines of formula R ⁇ NHNH not commercially available may be prepared by methods well documented in the literature
  • R and R l have the meanings given above and X is halo, suitably chloro, in a convenient solvent, such as N,N-d ⁇ methylformam ⁇ de, and in the presence of a base, such as potassium carbonate.
  • a convenient solvent such as N,N-d ⁇ methylformam ⁇ de
  • 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 R -CH 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)
  • Compounds of formula (IV) can be prepared by reacting the G ⁇ gnard reagent formed from magnesium, iodine and 4- bromo- l-(r-butyld ⁇ methyls ⁇ loxy)benzene with sodium pyruvate in tetrahydrofuran and treating the propionic acid so formed with ethyl iodide in NN-dimethyl formamide in the presence of diisopropylethylamine.
  • 4-Bromo- 1 -(t-butyldimethylsiloxy)benzene may be obtained by reacting 4-bromophenoi with t-butyl-dimethylsilylchloride in N,N-dimethyl formamide in the presence of imidazole.
  • compounds of formula (II) may be obtained by reacting the G ⁇ gnard 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 compounds of formula (I) are active fungicides and may be used to control one or more of the following pathogens: Pyricularia oryz e on rice and wheat and other Pyricitlaria 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.
  • mice 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.
  • cereals e.g. wheat
  • Didymella spp. on tomatoes, turf, wheat and other hosts Phoma spp. on oil-seed rape, turf, rice, potatoes, wheat and other hosts
  • BYMV barley yellow mosaic virus
  • 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 uefined 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 0.1 g 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 0.000 lg (for example 0.00 lg 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.
  • 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 alkyl naphthalenes, 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.
  • aqueous 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.
  • 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 (E)-N-methyl-2-(2-phenoxyphenyl)-2- methoxyiminoacetamide, (E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy- iminoacetamide, (R5 l-aminopropylphosphonic acid, (R5)-4-(4-chlorophenyl)- -2-phenyl-2-(lH-l,2,4-triazol-l-ylmethyl)butyronitrile, (Z)-N-but-2-enyloxymethyl- -2-chloro-2',6'-diethylacetanilide, l-(2-cyano-2-methoxyiminoacetyl)-3-ethyl urea,
  • 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, t ,t -di-wo-propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole.
  • dimethomorph dimethirimol, diniconazole, dinocap, dipyrithione, ditalimfos, dithianon, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, etaconazole. ethirimol. ethoxyquin, ethyl (Z)-N-benzyl-N-([methyl(methyl- thioethylideneamino-oxycarbonyl)am ⁇ no]thio)- ⁇ -alaninate, etridiazole, famoxadone, fenaminosulph, fenapanil.
  • fenarimol fenbuconazole, fenfuram, fenpiclonil, fenpropidin, fenpropimo h, fentin acetate, fentin hydroxide, ferba , ferimzone, fluazinam, fludioxonil, fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fuberidazoie, furalaxyl, furametpyr, furconazole-cis, guazatine, hexaconazole, hydroxyisoxazole, hymexazole, imazalil, imibenconazole, iminoctadine albesilate, ipconazole, iprobenfos, iprodione, isopropanyl butyl carbamate, isoprothiolane, kasugamycin, kresoxim-methyl
  • pefurazoate penconazole, pencycuron, phenazin oxide, phosetyl-Al, phosphorus acids, phthalidc, 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 quintozene, rabenazole, sodium pentachlorophenate, spiroxamine, streptomycin, sulphur, tebuconazole, techlofthalam, tecnazene, tetraconazole, thiabendazole, thicyofen, thifluzamide.
  • 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 crude oil (0.65 g, 1.23 mmol) was dissolved in dry dichloromethane (20 ml), and phenylhydrazine (280 mg, 2.6 mmol), acetic acid (0.18 g, 3.1 mmol), and sodium acetate (0.12 g, 1.5 mmol) added.
  • the resulting mixture was heated at reflux for 14 hours, then cooled to ambient temperature, and water added.
  • the mixture was extracted with dichloromethane, and the combined organic extracts washed with dilute hydrochloric acid and water, dried and evaporated.
  • the crude product was purified by flash chromatography, then triturated with hexane:ether to provide the title compound as a white powder (95 mg, 15%).
  • 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 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 app ed 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
  • the disease level present i.e. leaf area covered by actively sporulating disease
  • 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 28.

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Abstract

A fungicidal compound having general formula (I), wherein R1 is a N-or C-linked 5-membered heterocyclic ring containing from 2 to 4 heteroatoms selected from N, O and S, at least one of which is N, and which is optionally N- or C-substituted with one or more of halo, C¿1-6? alkyl, halo(C1-6)alkyl, C1-4 alkoxy(C1-6)alkyl, aryl(C1-6)alkyl, C1-6 alkoxy, halo(C1-6)alkoxy, 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 substitutents 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

SUBSTITUTED OXAZOLIDINEDIONES AND THEIR USE AS FUNGICIDES .
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 R' is a N- or C-linked 5-membered heterocyclic ring containing from 2 to 4 heteroatoms selected from Ν, O and S, at least one of which is Ν, and which is optionally N- or C-substituted with one or more of halo, C|.6 alkyl, halo(Cι.6)alkyl, C alkoxy(C|.6)alkyI, aryl(Cι.6)alkyl, C|.6 alkoxy, halo(C,.6)alkoxy, C|.6 alkylthio, C,.6 alkylcarbonyl, C|.6 alkylcarbonylarnino, C|.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(Cι.0)alkoxy, Cι. alkoxy (Cι.6)alkyl, nitro, amino. mono- or di(C|.4)alkylamino, cyano. Cι.„ alkoxycarbonyl or d.6 alkylcarbonyl, and R2 is phenyl, pyridyl, pyrimidinyi, pyridazinyl, pyrazinyl, triazinyl, pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl. thiazolyl, isothiazolyi, triazolyl, thiadiazolyl, oxadiazolyl or tetrazolyl, any of which is optionally substituted with one or more of halo, C|.D alkyl, halo(C|. 6)alkyl, C 6 alkoxy, halo(Cι.6)alkoxy, C|.6 alkylthio, nitro, cyano, thiocyanato, C alkylsulphonyl, halo(C )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, C<.4 alkyl or C 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
Figure imgf000004_0001
1. ethyl. /- and wo-propyl. n-, sec-, iso- and rr-butyl and /i-hexyl
Halo includes fluoro. chloro, bromo and iσdo. Most commonh it is fluoro or chloro Haloalkyl is typically tπfluoromethyl and haloalkoxy is typicalh tπfluoromethoxy Aryl is usually phenyl but also includes naphthyl
Heteroaryl includes the residues of 6-membered heteroaromatic rings containing irom 1 to 3 N atoms, eg pyπdyl. pyrimidinyi, pyrazinyl, pyridazinyl or 1.3.5-tridzιnyl. 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. isothiazolyi. isoxazolyl, pyrazolyl, imidazolyl, thiadiazolvi, oxadiazolvi or tπazolyl. Typically heteroaryl is pyπdyl, thienyl, furyl, pyrrolyl. isoxazolyl or isothiazolyi
The 5-membered heterocyclic ring R1 is suitably selected from thiazolyl, oxazolyl, isothiazolyi, isoxazolyl, pyrazolyl. imidazolyl, 1,2,3-, 1.2,4-, 1,2.5- and 1.3.4-th adιazolyl, 1,2,4-, 1.2,5- and 1,3,4-oxadιazolyl, 1,2,3- and 1,2,4-tπazolyl and tetrazolyl Typically R1 is 2-thιazolyl, 4-thιazolyl, 5-thιazolyl, 4-oxazolyl, 3-ιsoxazolyl, 4-ιsoxazolyl. 5-ιsoxazolyl, 1- imidazolyl, 2-ιmιdazolyl, 4-ιmιdazolyl, 5-ιmιdazolyl, 1-pyrazolyl.
Figure imgf000004_0002
4-pyrazolyl, 5- pyrazolyl, 3-(l,2,4-oxadιazolyl), 5-(l,2,4-oxadιazolyl), 4-(l,2,3-thιadιazolyn, 3-( 1,2,4- thιadιazolyl), 4-( l ,2.3-tπazolyl), 5-(l,2,3-tπazolyl), l-( 1.2,4-tπazolyl), 3-( 1.2,4-tπazolyl), 1- tetrazolyl or 5-tetrazolyl optionally C- or N-substituted with one or more of the R1 substituents listed above
Of particular interest are compounds in which R1 IS 2-thιazolyl optionally substituted with halo, C, 4 alkyl or halo(C, 4)alkyl; 4-thιazolyl optionally substituted in the 2-posιtιon with C, alkyl, halo(Cι-4)alkyl, Ci 4 alkoxy, halo(C, )alkoxy, C, 4 alkylcarbonylarmno, aryl or heteroaryl and in the 5-posιtιon with halo, Cι 4 alkyl or halo(C, )alkyl. 5-thιazoiyl optionally substituted in the 2-posιtιon with halo, Cι 4 alkyl, halo(C, 4)alkyl, Cι alkoxy. halo(G
4)alkoxy, aryl or heteroaryl and in the 4-posιtιon with halo, C, 4 alkyl or halo(Cι 4)alkyl, 3- lsothiazolyl optionally substituted with Ci alkyl, halo(C) )alkyl or aryl, 4-ιsothιazolyl optionally substituted with C,. alkyl, halo(G 4)alkyl or aryl, 5-ιsothιazolyl optionally substituted with C, 4 alkyl, halo(C) )alkyl or aryl, 2-oxazolyl optionally substituted with halo. C alkyl, halo(G 4)alkyl or aryl, 4-oxazolyl optionally substituted in the 2-posιtιon with Ci 4 alkyl. halo(Cι 4)alkyl. aryl or heteroaryl and in the 5-posιtιon with halo. C, 4 alkyl. aryl; 5-oxazolyl optionally substituted in the 2-position with C,.4 alkyl, halo(C|.4)alkyl, aryl or heteroaryl and in the 4-position with halo, C alkyl or halo(C|.4)alkyl; 3-isoxazolyl optionally substituted with C alkyl, halo(Cι.4)alkyl, C alkoxy (C,.4)alkyl, aryl or heteroaryl; 4-isoxazolyl optionally substituted with C|.4 alkyl, halo(Cι.4)alkyl, aryl or heteroaryl; 5-isoxazolyl optionally substituted with CM alkyl, halo(Cι.4)alkyl, C|.4 alkoxy(C|. 4)alkyl, aryl or heteroaryl; 1-imidazolyl optionally substituted with halo. C alkyl, halo(C|. 4)alkyl, nitro, C|.4 alkoxycarbonyl or aryl; 2-imidazolyl optionally substituted in the i-position with CM alkyl, halo(C].4)alkyl, aryl(Cι.4)alkyl or aryl and in any other position with halo, CM alkyl, halo(C|. )alkyl, nitro or Cι.4 alkoxycarbonyl; 4-imidazolyl optionally substituted in the 1-position with G.4 alkyl, halo(Cι-4)alkyl, aryl(C|.4)alkyl or aryl and in any other position with halo, C alkyl, halo(G.4)alkyl, C alkoxy(C|. )alkyl, nitro, C alkoxycarbonyl or aryl; 5- imidazolyi optionally substituted in the 1-position with C|.4 alkyl, halo(C|.4)alkyl. aryl(C|. 4)alkyl or aryl and in any other position with halo, CM alkyl, halo(Cι.4)alkyl, CM alkoxy(Cι. )alkyl, nitro. CM alkoxycarbonyl or aryl; 1-pyrazolyl optionally substituted with halo, C|.4 alkyl or halo(C). )alkyl; 3-pyrazolyl optionally substituted in the 1 -position with C|- alkyl, halo(Cι. )alkyi, aryl(C|.4)alkyl, CM alkylcarbonyl or arylcarbonyl and in any other position with halo, C,.4 alkyl, halo(C|. )alkyl or nitro; 4-pyrazolyl optionally substituted in the 1- position with C alkyl, halo(C|.4)alkyl, aryl(Cι.4)alkyl or aryl and in any other position with halo, CM alkyl, halo(C|.4)alkyl, C,. alkoxy(Cμ4)alkyl, aryl(C,.4)alkyl, Cι. alkoxy, halo(G. 4)alkoxy, aryl or aryloxy; 5-pyrazolyl optionally substituted in the 1-position with C alkyl, halo(C ) alkyl, aryl(C|. )alkyl or aryl and in any other position with halo, C alkyl or halo(C|.4)alkyl; 3-(l,2,4-oxadiazolyl) optionally substituted in the 5-position with CM alkyl, halo(C|. )alkyl, aryl or heteroaryl; 5-(l,2,4-oxadiazolyl) optionally substituted in the 3- position with CM alkyl, halo (Cι.4)alkyl, aryl or heteroaryl; 3-(l,2,5-oxadiazolyl) optionally substituted in the 4-position with C alkyl, halo(Cι.4)alkyl, CM alkoxy(Cι.4)alkyl, aryl or heteroaryl; 2-(l,3,4-oxadiazolyl) optionally substituted in the 5-position with C). alkyl, halo(Cι.4) alkyl, aryl or heteroaryl; 4-(l,2,3-thiadiazolyl) optionally substituted in the 5- position with halo, C alkyl, halo(Cι.4)alkyl, aryl or heteroaryl; 5-(l,2,3-thiadiazolyl) optionally substituted in the 4-position with halo, CM alkyl, halo(C|.4) alkyl, aryl or heteroaryl; 3-( l,2.4-thiadiazolyl) optionally substituted in the 5-position with halo, C alkyl, halo(Cι. )alkyl, C alkoxy, halo(C,.4)alkoxy, C:.4 alkylthio, aryl or heteroaryl; 5-( 1,2,4- thiadiazolvi) optionally substituted in the 3-position with halo. .4 alkyl, halo(C|. )alkyl, C alkoxy. halo(C|. )alkoxy, Cι.4 alkylthio, aryl or heteroaryl: 3-( 1.2.5-thiadiazolyl) optionally substituted in the 4-position with halo, C M alkyl, halo(C|. )alkyl. C alkoxy, halo(C|. )alkoxy, aryl or heteroaryl; 2-( l,3,4-thiadiazolyl) optionally substituted in the 5-position with halo, C|.4 alkyl, halo(Cι.4)alkyl, C|.4 alkoxy, halo(C|.4)alkoxy, Cι.4 alkylthio, aryl or heteroaryl; 1 -( 1 ,2,3-triazolyi) optionally substituted with C|.4 alkyl, halo(C )alkyl or aryl; 4-( 1,2,3- triazolyl) optionally substituted in the 1 -position with C,.4 alkyl. halo(Cι.4)alkyl or aryl and in the 5-position with C,.4 alkyl, halo(C )alkyl, Cι.4 alkoxycarbonyl or aryl; 5-(l ,2,3-triazolyl) optionally substituted in the 1 -position with CM alkyl, halo(C|.4)alkyl or aryl and in the 4- position with C|.4 alkyl, halo(C|.4)alkyl, Cι. alkoxycarbonyl or aryl; l -( l ,2.4-triazolyl) optionally substituted with C alkyl, halo(C )alkyl or aryl; 3-( l ,2.4-triazolyl) optionally substituted in the 1 -position with C1.4 alkyl, halo(Cι.4)alkyl or aryl and in the 5-position with C alkyl, halo(C|.4)alkyl. C M alkoxy (Cι.4)alkyl, aryl or heteroaryl; 4-( l,2,4-triazolyl) optionally substituted with C alkyl, halo(Cι.4)alkyl or aryl; 5-( l,2,4-tπazolyl) optionally substituted in the 1 -position with C alkyl, halo(Cι-4)alkyl or aryl and in the 3-position with C|.4 alkyl, halo(C|.4)alkyl, C alkoxy(C,. )alkyl, aryl or heteroaryl; 1-tetrazolyl optionally substituted in the 5-position with C alkyl, Cι.4 alkylthio or aryl; 2-tetrazolyl optionally substituted in the 5-position with C|. alkyl, C M alkylthio or aryl; or 5-tetrazolyl optionally substituted with d.4 alkyl or aryl. The aryl or heteroaryl substituent of the 5-membered heterocyclic ring R1 may be any aryl or heteroaryl group defined above and may be optionally substituted with one or more of halo, C alkyl, halo(C|. )alkyl, C alkoxy, halo(C,.4)alkoxy, CM alkoxy(Ci.4)alkyl, nitro, amino. mono- or di(Cι.4)alkylamino, cyano, C,.4 alkoxycarbonyl or C 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(C )alkoxy, C alkylthio, nitro, cyano, thiocyanato, C|.4 alkylsulphonyl, halo(C|. )alkylsulphonyl, aminosulphonyl or CM alkoxycarbonyl, or naphthyl. Alternatively, R: 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-tnazolyl), 5-( l ,2,3-thiadiazolyl) or 5-tetrazolyl, any of which is optionally substituted with 1 to 3 substituents selected from halo, C M alkyl, halo(C|.4)alkyl, C M alkoxy, halo(C )alkoxy, nitro, cyano, phenyl. C alkylsulphonyl or C alkoxycarbonyl or, in the case of pyπdyl, with 4 fluorine or chlorine atoms. As a further alternative R2 is, for example, 2-, 3- or 4-quιnolιnyl, 4-quιnazohnyl, 1- phthalazinyl, 2-qumoxalιnyl, 3-(l,2,4-benzotπazιnyl), 2-benzoxazolyl or 2-benzothiazolyl, any of which is optionally substituted in its fused benzene πng with halo, C|.4 alkyl, C1-4 alkoxy or nitro and in its heterocyclic ring with halo, CM alkyl, halo(G 4)alkyl,
Figure imgf000007_0001
4 alkoxy, halo(G )alkoxy, nitro, cyano, G 4 alkylsulphonyl or C|.4 alkoxycarbonyl. The present invention is illustrated by the compounds of general formula (I) listed in
Tables 1 to 30 which follow
TABLE 1
Table 1 comprises 167 compounds of the general formula (I), wherein R1 is 2-thiazolyl and R: has the value listed below.
Figure imgf000008_0001
Figure imgf000009_0001
Figure imgf000010_0001
Compound No. K
143 2-CO2CH3-4-SO2C3H7-thien-3-yl 144 4-CO2C2H5-5-CH3-pyrazol-3-yl
145 3-CH3-4-CO2C2H5-ρyrazol-5-yl 146 1 ,3-(CH3)2-4-NO2-pyrazol-5-yl 147 4-C6H5-thiazol-2-yl 148 5-CH3-l,2,4-triazol-3-yl 149 4-CO2C2H5- 1 ,2,3-thiadiazol-5-y 1 150 tetrazol-5-yl 151 benzoxazol-2-yl 152 benzothiazol-2-yl
153 4-CH3-benzothiazol-2-yl 154 6-NO2-benzothiazol-2-yl
155
Figure imgf000011_0001
TABLE 2
Table 2 comprises 167 compounds of the general formula (I), wherein R1 is 2-methyl- 4-thiazolyl 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 R1 is 2-(5- isoxazolyl)-4-thiazolyl 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 2-chloro- 5-thiazolyi and R2 has the value listed for the correspondingly numbered compound in Table TABLE 5
Table 5 comprises 167 compounds of the general formula (I), wherein R1 is 2-methyl- 5-(2-nitrophenyl)-4-oxazolyl 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 3,5- dimethyl-4-isoxazolyl 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 R1 is 5-methyl-
3-isoxazolyl 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 3-phenyl- 5-isoxazolyl and R2 has the value listed for the correspondingly numbered compound in Table I.
TABLE 9 Table 9 comprises 167 compounds of the general formula (I), wherein R1 is 4,5- dichloro-1 -imidazolyl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 10
Table 10 comprises 167 compounds of the general formula (I), wherein R1 is 2- imidazolyl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 11 Table 1 1 comprises 167 compounds of the general formula (I), wherein R1 is l-iso- propyl-2-imidazolyl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 12 Table 12 comprises 167 compounds of the general formula (I), wherein R1 is 1- methyl-4-nitro-2-imidazolyl 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 4- imidazolyl 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 4- methyl-5-imidazoiyl 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 2- methyl-4-imidazolyl 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 R' is 3,5- dimethyl- 1 -pyrazolyl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 17 Table 17 comprises 167 compounds of the general formula (I), wherein R1 is 1- methyl-4-chloro-3-pyrazolyl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 18 Table 18 comprises 167 compounds of the general formula (I), wherein R1 is 4-nitro- 5-methyl-3-pyrazolyl and R2 has the value listed for the correspondingly numbered compound in Table 1. TABLE 19
Table 19 comprises 167 compounds of the general formula (I), wherein R1 is 1,5- dimethyl-4-pyrazolyl and R2 has the value listed for the correspondingly numbered compound in Table 1. TABLE 20
Table 20 comprises 167 compounds of the general formula (I), wherein R1 is 1 ,3- dimethyl-4-pyrazolyl and R" has the value listed for the correspondingly numbered compound in Table 1. TABLE 21
Table 21 comprises 167 compounds of the general formula (I), wherein R1 is 3.5- dimethyl-4-pyrazolyl and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 22 Table 22 comprises 167 compounds of the general formula (I), wherein R1 is 3- methyl-5-pyrazolyl and R: has the value listed for the correspondingly numbered compound in Table 1.
TABLE 23 Table 23 comprises 167 compounds of the general formula (I), wherein R' is 3-( l ,2,4- oxadiazolyl) and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 24 Table 24 comprises 167 compounds of the general formula (I), wherein R1 is 5- phenyl-3-(l ,2,4-oxadiazolyl) and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 25 Table 25 comprises 167 compounds of the general formula (I), wherein R1 is 5-(4- trifluoromethylphenyl)-3-(l,2,4-oxadiazolyl) and R2 has the value listed for the correspondingly numbered compound in Table 1. TABLE 26
Table 26 comprises 167 compounds of the general formula (I), wherein R1 is 5-(3,5- dimethyl-4-isoxazolyl)-3-( l,2,4-oxadiazolyl) and R2 has the value listed for the correspondingly numbered compound in Table 1. TABLE 27
Table 27 comprises 167 compounds of the general formula (I), wherein R' is 5-chloro- 4-( 1.2,3-thiadiazolyl) and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 28
Table 28 comprises 167 compounds of the general formula (I), wherein R1 is 1- phenyl-4-(l,2,3-triazolyl) and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 29
Table 29 comprises 167 compounds of the general formula (I), wherein R1 is l-( 1,2,4- triazolyl) and R2 has the value listed for the correspondingly numbered compound in Table 1.
TABLE 30
Table 30 comprises 167 compounds of the general formula (I), wherein R' is 3-( 1 ,2,4- triazolyl) 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 imgf000015_0001
in which R' has the meaning given above and R is, for example, CM alkyl, suitably ethyl, with a carbonylating agent, suitably 1 , r-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 bπne 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'-carbonyldumidazole. are commercially available, as are many hydrazines of formula R2NHNH2 Hydrazines of formula R~NHNH 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 imgf000016_0001
with a compound of the formula R'-CH2X, in which R and Rl have the meanings given above and X is halo, suitably chloro, in a convenient solvent, such as N,N-dιmethylformamιde, 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 R -CH2X 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 imgf000017_0001
in which TBDMSO is r-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 Gπgnard reagent formed from magnesium, iodine and 4- bromo- l-(r-butyldιmethylsιloxy)benzene with sodium pyruvate in tetrahydrofuran and treating the propionic acid so formed with ethyl iodide in NN-dimethyl formamide in the presence of diisopropylethylamine. 4-Bromo- 1 -(t-butyldimethylsiloxy)benzene may be obtained by reacting 4-bromophenoi 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 Gπgnard reagent formed from magnesium and a compound of formula (V):
Figure imgf000017_0002
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-039391 1 and US Statutory Invention Registration No. HI 401. 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 oryz e on rice and wheat and other Pyricitlaria 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; Altemaria 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; Fusahum 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 Pyήcularia 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 uefined 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 0.1 g 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 0.000 lg (for example 0.00 lg 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 alkyl naphthalenes, 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 (E)-N-methyl-2-(2-phenoxyphenyl)-2- methoxyiminoacetamide, (E)-N-methyl-2-[2-(2,5-dimethylphenoxymethyl)phenyl]-2-methoxy- iminoacetamide, (R5 l-aminopropylphosphonic acid, (R5)-4-(4-chlorophenyl)- -2-phenyl-2-(lH-l,2,4-triazol-l-ylmethyl)butyronitrile, (Z)-N-but-2-enyloxymethyl- -2-chloro-2',6'-diethylacetanilide, l-(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-trifluoromethylbenzimidazole-l-sulphonamide, 5-ethyl-5,8-dihydro-8-oxo( l,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, benomyi, 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, t ,t -di-wo-propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole. dimethomorph, dimethirimol, diniconazole, dinocap, dipyrithione, ditalimfos, dithianon, dodemorph, dodine, doguadine, edifenphos, epoxiconazole, etaconazole. ethirimol. ethoxyquin, ethyl (Z)-N-benzyl-N-([methyl(methyl- thioethylideneamino-oxycarbonyl)amιno]thio)-β-alaninate, etridiazole, famoxadone, fenaminosulph, fenapanil. fenarimol, fenbuconazole, fenfuram, fenpiclonil, fenpropidin, fenpropimo h, fentin acetate, fentin hydroxide, ferba , ferimzone, fluazinam, fludioxonil, fluoroimide, fluquinconazole, flusilazole, flutolanil, flutriafol, folpet, fuberidazoie, furalaxyl, furametpyr, furconazole-cis, guazatine, hexaconazole, hydroxyisoxazole, 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, MOΝ41 100, myclobutanil, NTN0301, neoasozin, nickel dimethyldithiocarbamate, nitrothai-isopropyl, nuarimol, ofurace, organomercury compounds, oxadixyl, oxolinic acid, oxycarboxin. pefurazoate, penconazole, pencycuron, phenazin oxide, phosetyl-Al, phosphorus acids, phthalidc, 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 1 , -iminodi(octamethylene)diguanidine, triadimefon, triadimenol, iriazbutyl, 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-(3,5-dιmethyl-4- ιsoxazolylmethoxy)phenyl]-3-phenylamιno-l,3-oxazolιdme-2,4-dιone (Compound 1 of Table
6).
Preparation of 4-bromo- 1 -(t-butyldimethylsiloxy)benzene Imidazole (70 7 g, 1.04 mol) was added in one portion to a stirred solution of t- butyldimethylsilyl chloπde (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-/-butyldimethylsiloxyphenyl)-2-hydroxypropιonιc 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-(t-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- butyidimethylsiloxy)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).
Η 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-t-butyldimethylsiloxyphenyl)-2-hydroxypropionate
A solution of 2-(4-t-butyldimethylsiloxyphenyl)-2-hydroxypropionic acid (70 g, 0.24 mol), di røpropylethylamine (46 g, 0.35 mol) and ethyl iodide (55 g, 0.35 mol) in dry dimethyl formamide (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 (CDC13) 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 ( 1M in tetrahydrofuran; 446 ml, 0.446 mol) was added to a stirred solution of ethyl 2-(4-/-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%).
Η nmr (CDCh) δ 1.25 (3H, t), 1.76 (3H, s), 3.87 ( I H, s), 4.22 2H. m), 5.70
( IH, br s), 6.79 (2H, d), 7.40 (2H. d) ppm.
Preparation of ethyl 2-[4-(3,5-dimethyl-4-isoxazolylmethoxy)phenyl]-2-hydroxypropιonate
A mixture of ethyl 2-hydroxy-2-(4-hydroxyphenyl)propionate ( 1.00 g, 4.76 mmol), 4- (chloromethyl)-3,5-dimethylisoxazole (693 mg, 4.76 mmol), potassium carbonate (657 mg, 4.76 mmol) and dry dimethylformamide (10 ml) was stirred at 60 °C for 4 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 ( 1.06 g, 70%).
Η nmr(CDCl3) δ 1.27 (3H, t), 1.78 (3H, s), 2.29 (3H, s), 2.40 (3H, s), 3.80
(IH, s), 4.22 (2H, m), 4.79 (2H, s), 6.92 (2H, d), 7.51 (2H, d) ppm.
Preparation of 5-[4-(3,5-dimethyl-4-isoxazolylmethoxy)phenyl]-5-methyl-3-phenylamino- 1 ,3- oxazolidine-2.4-dione
A solution of ethyl 2-[4-(3,5-dimethyl-4-isoxazolylmethoxy)phenyl]-2- hydroxypropionate (910 mg, 2.8 mmol) and l.T-carbonyldiimidazoIe (832 mg, 5.13 mmol) in dry dichloromethane (20 ml) was heated at reflux for 4 hours, then cooled to ambient temperature and poured into water. The mixture was extracted with ethyl acetate, and the combined organic extracts washed with brine, dried and evaporated. The residue was dissolved in dry dichloromethane (15 ml), and phenylhydrazine (376 mg, 3.5 mmol) and acetic acid (0.26 ml, 4.3 mmol) added. The resulting solution was allowed to stand at ambient temperature for 2 days then poured into water and extracted with dichloromethane. The combined organic extracts were washed with brine, dried and evaporated. The crude product was purified by flash chromatography, then triturated with hexane to provide the title compound as a powder (516 mg, 44%).
m.p. 86.5 - 88.5 °C.
EXAMPLE 2 This Example illustrates the preparation of 5-methyl-5-[4-(2-methyl-4-thiazolyl- methoxy)phenyl]-3-phenylamino-l,3-oxazolidine-2,4-dione (Compound 1 of Table 2).
Preparation of ethyl 2-hydroxy-2-[4-(2-methyl-4-thiazolylmethoxy)phenyl]propionate
A mixture of ethyl 2-hydroxy-2-(4-hydroxyphenyl)propionate (2.0 g, 9.5 mmol; prepared as described in Example 1), 4-(chloromethyl)-2-methylthiazole hydrochloride (1.75 g, 9.5 mmol), potassium carbonate (2.63 mg, 19 mmol) and dry acetone (30 ml) was stirred at reflux for 6 hours. The mixture was cooled to ambient temperature, poured into water and extracted with ether. 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 gum ( 1.94 g, 63%).
Η nmr(CDCl3) δ 1.27 (3H, t), 1.77 (3H, s), 2.73 (3H, s), 3.79 (IH, s), 4.21
(2H, m), 5.13 (2H, s), 6.97 (2H, d), 7.14 (IH, s), 7.48 (2H, d) ppm.
Preparation of 5-methyl-5-[4-(2-methyl-4-thiazolylmethoxy)phenyl]-3-phenylamino- 1 ,3- oxazolidine-2,4-dione A solution of ethyl 2-hydroxy-2-[4-(2-methyl-4-thiazolylmethoxy)phenyl]propionate ( 1.9 g, 5.9 mmol) and l. r-carbonyldiimidazole ( 1.72 g, 10.6 mmol) in dry dichloromethane (20 ml) was heated at reflux for 6 hours, then cooled to ambient temperature and poured into water. The phases were separated and the aqueous extracted with dichloromethane. The combined organic extracts were washed with water, dried and evaporated.
The residue was dissolved in dry dichloromethane (20 ml), and phenylhydrazine (780 mg, 7.2 mmol) and acetic acid (0.52 ml, 9.0 mmol) added. The resulting solution was stirred at ambient temperature for 24 hours. The phases were separated and the organic phase was washed with dilute hydrochloric acid, aqueous sodium bicarbonate and brine, dried and evaporated. The crude product was purified by flash chromatography, then triturated with hexane to provide the title compound as a powder (930 mg, 38%).
m.p. 141 - 143 °C.
EXAMPLE 3 The following compounds were prepared using the method of Example 2:
Compound Table Melting point or nmr data
1 26 δ 1.95 (3H, s), 2.56 (3H, s), 2.79 (3H, s), 5.26 (2H, s), 6.38
( IH, s), 6.70 (2H, d), 6.97 ( IH, t), 7.09 (2H, d), 7.21 (2H, t),
7.52 (2H, t) ppm. 1 7 δ 1.95 (3H. s). 2.45 (3H, s), 5.15 (2H, s), 6.10 (IH, s), 6.15
( IH, s), 6.75 (2H. d), 7.00 (3H, m), 7.25 (2H, m), 7.50 (2H, m) ppm.
EXAMPLE 4
This Example illustrates the preparation of 5-methyl-5-[4-(2-methyl-4-thiazolylmethoxy)- pheπyl]-3-(4-t-butyiphenyl)amino- l ,3-oxazolidine-2,4-dione (Compound 42 of Table 2)
Preparation of 5-methyl-5-[4-(2-methyl-4-thiazolylmethoxy)phenyl]-3-(4-t-butylphenyl)- amino- l,3-oxazolidine-2,4-dione
A solution of ethyl 2-hydroxy-2-[4-(2-methyl-4-thiazolylmethoxy)phenyl]propionate (14.65 g, 45.4 mmol) and l.r-carbonyldiimidazole (8.9 g, 54.8 mmol) in dry dichloromethane (500 ml) was heated at reflux for 18 hours. Further l, -carbonyldiimidazole (2.0 g, 12.3 mmol) and the mixture heated at reflux for a further 4 hours, then cooled to ambient temperature and washed with water, dried and evaporated to leave a clear oil.
The intermediate (0.30 g, 0.74 mmol) was dissolved in dry dichloromethane (6 ml) and added to 4-t-butylphenylhydrazine (144 mg, 0.88 mmol), followed by triethylamine (0.1 ml. 0.7 mmol) and acetic acid (0.15 ml, 2.6 mmol). The resulting solution was stirred at ambient temperature for 48 hours, then evaporated. Ethyl acetate and 2N hydrochloric acid were added, the phases were separated and the organic phase was washed with water, dried and evaporated. The crude product was purified by chromatography to provide the title compound as a powder.
m.p. 189 - 190 °C.
EXAMPLE 5
The following compounds were prepared using the method of Example 4:
Compound Table No Melting point, nmr or mass spectrometry data
14 2 δ 1.95 (3H, s), 2.56 (3H, s), 2.79 (3H, s), 5.26 (2H, s),
6.38 (IH, s), 6.70 (2H, d), 6.97 ( IH, t), 7.09 (2H, d), 7.21 (2H, t), 7.52 (2H, t) ppm.
36 2 111 - 113 °C
37 2 121 - 123 °C
2 2 δ 1.98 (3H, s), 2.75 (3H, s), 5.16 (2H, s), 6.36 (IH, d),
6.59 ( IH, m), 6.9 - 7.1 (4H, m), 7.16 ( IH, s), 7.48 (3H, m) ppm. 5 2 δ 1.99 (3H, s), 2.75 (3H, s), 5.17 (2H, s), 6.46 (IH, d),
6.50 (IH, d), 6.61 ( IH, s), 6.90 (2H, m), 7.05 (2H, d),
7.15 (lH, s), 7.50 (2H, d) ppm. 54 2 143 - 145 °C
23 2 δ 1.98 (3H, s), 2.74 (3H, s), 5.16 (2H, s), 6.43 (IH, s),
6.54 ( IH, d), 6.95 ( IH, m), 7.02 (3H, m), 7.15 (IH, s),
7.45 (2H, d) ppm. 10 2 140 - 142 °C
7 2 136 - 138 °C
65 2 143 - 145 °C
121 2 δ 2.05 (3H, s), 2.74 (3H, s), 5.16 (2H, s), 6.70 ( IH, d),
7.03 (2H, d), 7.16 ( IH, s), 7.52 (2H, d), 7.60 ( IH. br s),
7.72 (lH. m), 8.40 (IH, s) ppm. 35 2 110 - 1 12 °C 124 - 127 °C
121 - 124 °C
1 10 - 112 °C
Figure imgf000031_0001
δ 1.94 (3H, s), 2.73 (3H. s), 5.15 (2H. s i, 6.52 ( IH. d).
6.94 (2H, m), 6.96 (2H. d), 7.14 ( I H. ». 7.16 ( IH, mj,
7.46 (2H, d) ppm.
56 2 δ 1.99 (3H, s), 2.26 (3H, s), 2.75 (3H. S ). 5.17 (2H. s ),
6.05 ( IH, s), 6.15 ( IH, dd), 6.61 ( I H. dπ. 7.04 (2H. d), 7.05 ( IH, m), 7.17 ( IH. s), 7.50 (2H. d ppm.
6 2 132 - 134 °C
128 2 M+ 492
1 1 2 δ 1.95 (3H, s), 2.45 (3H, s), 5.15 (2H. si. 6.10 ( IH, s ),
6.15 ( IH, s), 6.75 (2H, d), 7.00 (3H. mi. 7.25 (2H, m), 7.50 (2H, m) ppm.
EXAMPLE 6
This Example illustrates the preparation of 5-methyl-5-[4-( l ,2.4-oxadiazol-3- ylmethoxy)phenyl]-3-phenylamino- l,3-oxazolidine-2,4-dione (Compound 1 of Table 23)
Preparation of 5-methyl-5-[4-( 1 ,2,4-oxadiazol-3-ylmethoxy)phenyl]-3-phenylamino- 1 ,3- oxazolidine-2,4-dione
A solution of ethyl 2-[4-( l,2,4-oxadiazol-3-ylmethoxy)phenyl]-2-hydroxypropionate
(prepared by a method analogous to that described in Example 2) ( 1.4 g. 4.8 mmol) and 1 ,1 '- carbonyldiimidazole (1.32 mg, 8.16 mmol) in dry dichloromethane (20 ml) was heated at reflux for 3 hours, 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.
The residue was dissolved in dry dichloromethane ( 15 ml), and phenylhydrazine (298 mg, 2.76 mmol) and acetic acid (0.2 ml, 3.5 mmol) added. The resulting solution was heated at reflux for 10 hours, then cooled to ambient temperature, and dichloromethane added. The mixture was washed with dilute hydrochloric acid, aqueous sodium bicarbonate, water, and brine, dried and evaporated. The crude product was purified by flash chromatography, then crystallised from hexane:ethyl acetate to provide the title compound as a white powder ( 187 mg)- m.p. 140 - 141 °C.
EXAMPLE 7
5-[4-(2-Chloro-5-thiazolylmethoxy)phenyl]-5-methyl-3-phenylamino-l,3-oxazolidine-2,4- dione (Compound 1 of Table 4) was prepared by a similar method to that used in Example 6 (m.p. 177 - 178 °C).
EXAMPLE 8 This Example illustrates the preparation of 5-methyl-5-[4-(5-{4-trifluoromethylphenyl}- 1,2,4- oxadiazol-3-ylmethoxy)phenyl]-3-phenylamino-l,3-oxazolidine-2,4-dione (Compound 1 of Table 25)
Preparation of 5-methyl-5-[4-(5-{4-trifluoromethylphenyl }-l,2,4-oxadiazol-3- ylmethoxy)phenyl]-3-phenylamino- 1 ,3-oxazolidine-2,4-dione
A solution of ethyl 2-[4-(5-{4-trifluoromethylphenyl}-l,2,4-oxadiazol-3-ylmethoxy)phenyl]- 2-hydroxypropionate (prepared by a method analogous to that described in Example 2) (1.0 g, 2.3 mmol) and l. l '-carbonyldiimidazole (0.7 g, 4.1 mmol) in dry dichloromethane (50 ml) was heated at reflux for 1 1 hours, then cooled to ambient temperature and poured into water. The phases were separated and the organic washed with water, dried and evaporated to leave a clear oil (1.2 g).
The crude oil (0.65 g, 1.23 mmol) was dissolved in dry dichloromethane (20 ml), and phenylhydrazine (280 mg, 2.6 mmol), acetic acid (0.18 g, 3.1 mmol), and sodium acetate (0.12 g, 1.5 mmol) added. The resulting mixture was heated at reflux for 14 hours, then cooled to ambient temperature, and water added. The mixture was extracted with dichloromethane, and the combined organic extracts washed with dilute hydrochloric acid and water, dried and evaporated. The crude product was purified by flash chromatography, then triturated with hexane:ether to provide the title compound as a white powder (95 mg, 15%).
m.p. 126 - 128 °C. EXAMPLE 9 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 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 app ed 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 Disese 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 28.
TABLE 28
Figure imgf000034_0001
Figure imgf000035_0001
Key to Diseases
LEPTNO Septona nodorum PLASVI Plasmopara viticola
PUCCRT Puccinia recondita PHYTIN Phytophthora infestans lycopersici

Claims

1 A compound having the general formula (I):
Figure imgf000036_0001
wherein R1 is a N- or C-hnked 5-membered heterocyclic πng containing from 2 to 4 heteroatoms selected from Ν, O and S, at least one of which is Ν, and which is optionally N- or C-substituted with one or more of halo, G.6 alkyl, haio(C, 6)alkyl, G 4 alkoxy(G.6)alkyl, aryl(G ft)alkyl, G.6 alkoxy, halo(G 6)alkoxy, G 6 alkylthio, G 0 alkylcarbonyl, G 6 alkylcarbonylamino, G.6 alkoxycarbonyl, arylcarbonyl, aryl, aryloxy, or heteroaryl, the aryl and heteroaryl substituents themselves being optionally substituted with one or more of halo, G.6 alkyl, halo(G.6)alkyl, G.6 alkoxy, halo(G. 6)alkoxy, CM alkoxy(G.6)alkyl, nitro, amino, mono- or di(G. )alkylamιno, cyano, G 6 alkoxycarbonyl or G e alkylcarbonyl, and R2 is phenyl, pyridyl, pyπmidinyl, pyπdazinyl, pyrazinyl, tπazinyl, pyrrolyl, furyl, thienyl, pyrazolyl, imidazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyi, tπazolyl, thiadiazolyl, oxadiazolyl or tetrazolyl, any of which is optionally subsututed with one or more of halo, G.6 alkyl, halo(G.6)alkyl, G.6 alkoxy, halo(G 6)alkoxy, G.6 alkylthio, nitro, cyano, thiocyanato, C M alkylsulphonyl, halo(G.4)alkylsulphonyl, aminosulphonyl or G.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, G.4 alkyl or C|.4 alkoxy. 2. A compound according to claim 1 in which the 5-membered heterocyclic ring R1 is selected from 2-thιazolyl, 4-thiazolyl, 5-thiazolyl, 4-oxazolyl, 3-ιsoxazolyl, 4- lsoxazolyl, 5-ιsoxazolyl, 1-imidazolyl, 2-imidazolyl, 4-imιdazolyl, 5-imιdazolyl, 1- pyrazolyl. 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl, 3-(l,2,4-oxadιazolyl), 5-( 1,2,4- oxadiazolyl), 4-( 1.2,3-thiadiazolyl), 3-(l,2,4-thiadiazolyl), 4-(l,2,3-tπazolyl), 5- ( 1 ,2,3-triazolyl), l -( l ,2,4-triazolyl), 3-( l,
2.4-triazolyl), I -tetrazolyl or 5-tetrazolyl optionally C- or N-substituted with one or more of the R1 substituents listed in claim
3. A compound according to claim 1 in which R1 is 2-thiazolyl optionally substituted with halo, C,.4 alkyl or halo(G.4)alkyl; 4-thιazolyl optionally substituted in the 2- position with G. alkyl, halo(C1.4)alkyl, CM alkoxy, halo(G. )alkoxy, G.4 alkylcarbonylamino, aryl or heteroaryl and in the 5-position with halo, G.4 alkyl or halo(G.4)alkyl; 5-thiazolyl optionally substituted in the 2-position with halo G- alkyl, halo(C|.4)alkyl, G-4 alkoxy, halo(G.4)alkoxy, aryl or heteroaryl and in the 4-position with halo, G_ alkyl or halo(G. )alkyl; 3-isothiazolyl optionally substituted with G-4 alkyl, halo(G.4)alkyl or aryl; 4-isothiazolyl optionally substituted with Cμ alkyl, halo(G. )alkyl or aryl; 5-isothiazolyl optionally substituted with G-4 alkyl. halo(G. 4)alkyl or aryl; 2-oxazolyl optionally substituted with halo. CM alkyl, halo(G.4)alkyl or aryl; 4-oxazolyl optionally substituted in the 2-position with G.4 alkyl. halo(C|.
4)alkyl, aryl or heteroaryl and in the 5-position with halo, G.4 alkyl, halo(G.4)alkyl or aryl; 5-oxazolyl optionally substituted in the 2-position with G.4 alkyl, halo(G. )alkyl, aryl or heteroaryl and in the 4-position with halo, G-4 alkyl or halo(G. )alkyl; 3- isoxazolyl optionally substituted with G-4 alkyl, halo(G.4)alkyl, G. alkoxy (G. )alkyl, aryl or heteroaryl; 4-isoxazolyl optionally substituted with C alkyl, halo(C|. )alkyl, aryl or heteroaryl; 5-isoxazolyl optionally substituted with G. alkyl, halo(C|.4)alkyl, G-4 alkoxy(G. )alkyl, aryl or heteroaryl; 1-imidazolyl optionally substituted with halo, G. alkyl, halo(C|.4)alkyI, nitro, G. alkoxycarbonyl or aryl; 2-imidazolyl optionally substituted in the 1-position with G. alkyl, halo(G. )alkyl, aryl(G.4)alkyl or aryl and in any other position with halo, G.4 alkyl, halo(G. )alkyl, nitro or C alkoxycarbonyl; 4-imidazolyl optionally substituted in the 1 -position with G. alkyl, halo(Cι. )alkyl, aryl(CM)alkyl or aryl and in any other position with halo, G-4 alkyl, halo(G. )alkyl, G.4 alkoxy (G.4)alkyl, nitro, G-4 alkoxycarbonyl or aryl; 5-imidazolyl optionally substituted in the 1 -position with CM alkyl, halo(G.4)alkyl, aryl(C1.4)alkyl or aryl and in any other position with halo, G.4 alkyl, halo(C,.4)alkyl, G.4 alkoxy(G.
4)alkyl. nitro, G.4 alkoxycarbonyl or aryl; 1 -pyrazolyl optionally substituted with halo, Cι-4 alkyl or halo(G.4)alkyl; 3-pyrazolyl optionally substituted in the 1-position with C alkyl, halo(G. )alkyl, aryl(C|.4)alkyl, G.4 alkylcarbonyl or arylcarbonyl and in any other position with halo, G- alkyl, halo(G. )alkyl or nitro; 4-pyrazolyl optionally substituted in the 1-position with G-4 alkyl, halo(C|.4)alkyl, aryl(G.4)alkyl or aryl and in any other position with halo, C alkyl, halo(C|.4)alkyl, G-4 alkoxy (G. )alkyl, aryl(Cι.4)alkyl, G-4 alkoxy, halo(G.4)alkoxy, aryl or aryloxy; 5-pyrazolyl optionally substituted in the 1 -position with G-4 alkyl, halo(Cι.4)alkyl, aryl(G.4)alkyl or aryl and in any other position with halo, G.4 alkyl or halo(G.4)alkyl; 3-(l,2,4-oxadiazolyl) optionally substituted in the 5-position with G.4 alkyl, halo(G. )alkyl, aryl or heteroaryl; 5-( 1 ,2,4-oxadiazolyl) optionally substituted in the 3-position with G.4 alkyl, halo (C,.4)alkyl, aryl or heteroaryl; 3-( l,2,5-oxadiazolyl) optionally substituted in the 4-position with G. alkyl, halo(G.4)alkyl, G.4 alkoxy(G.4)alkyl, aryl or heteroaryl; 2-( l ,3,4-oxadiazolyl) optionally substituted in the 5-position with G-4 alkyl, halo(G_4) alkyl, aryl or heteroaryl; 4-(l,2,3-thiadiazolyl) optionally substituted in the 5-position with halo, C|.4 alkyl, halo(G.4)alkyl, aryl or heteroaryl; 5-( 1,2,3- thiadiazolyl) optionally substituted in the 4-position with halo, G-4 alkyl, halo(G-4) alkyl, aryl or heteroaryl; 3-( l,2,4-thiadiazolyl) optionally substituted in the 5-position with halo, G-4 alkyl, halo(G.4)alkyl, C|. alkoxy, halo(Cι.4)alkoxy, G-4 alkylthio, aryl or heteroaryl; 5-(l,2,4-thiadiazolyl) optionally substituted in the 3-position with halo, G-4 alkyl, halo(G. )alkyl, CI-4 alkoxy, halo(G-4)alkoxy, C,.4 alkylthio, aryl or heteroaryl; 3-( l,2,5-thiadiazolyl) optionally substituted in the 4-position with halo, G. 4 alkyl, halo(Cι. )alkyl, G-4 alkoxy, halo(C,.4)alkoxy, aryl or heteroaryl; 2-( 1,3,4- thiadiazolyl) optionally substituted in the 5-position with halo, CM alkyl, halo(G. 4)alkyl, C alkoxy, halo(G. )alkoxy, C|.4 alkylthio, aryl or heteroaryl; 1 -(1,2,3- triazolyl) optionally substituted with C alkyl, halo(G.4)alkyl or aryl; 4-( 1,2,3- triazolyl) optionally substituted in the 1-position with G. alkyl, halo(G-4)alkyl or aryl and in the 5-position with G-4 alkyl, halo(G.4)alkyl, Cι.4 alkoxycarbonyl or aryl; 5- (1,2,3-triazolyl) optionally substituted in the 1-position with G-4 alkyl, halo(G.4)alkyl or aryl and in the 4-position with G. alkyl, halo(G.4)alkyl, Cι.4 alkoxycarbonyl or aryl; l-(l,2,4-triazolyl) optionally substituted with CM alkyl, halo(G. )alkyl or aryl; 3-
( 1.2,4-triazolyl) optionally substituted in the 1-position with G. alkyl, halo(G.4)alkyl or aryl and in the 5-position with G-4 alkyl. halo(G.4)alkyl, C,.4 alkoxy(G.4)alkyl. aryl or heteroaryl; 4-( 1 ,2,4-triazolyϊ) optionally substituted with C alkyl, halo(G.4)alkyl or aryl; 5-(l,2,4-triazolyl) optionally substituted in the 1-position with G. alkyl, halo(C,.4)alkyl or aryl and in the 3-position with G.4 alkyl. halo(C|.4)alkyl, G-4 alkoxy(C|.4)alkyl, aryl or heteroaryl; I-tetrazolyl optionally substituted in the 5- position with G.4 alkyl, G-4 alkylthio or aryl; 2-tetrazolyl optionally substituted in the 5-position with CM alkyl, G. alkylthio or aryl; or 5-tetrazolyl optionally substituted with CM alkyl or aryl. The aryl or heteroaryl substituent of the 5-membered heterocyclic ring R1 may be any aryl or heteroaryl group defined above and may be optionally substituted with one or more of halo, C M alkyl, halo(G.4)alkyI, G. alkoxy, halo(G.4)alkoxy, G.4 alkoxy(G.4)alkyl, nitro, amino, mono- or di(G. 4)alkyiamino, cyano, G.4 alkoxycarbonyl or G.4 alkylcarbonyl.
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, CM alkyl, halo(G-4)alkyl, C,.4 alkoxy, halo(G. )alkoxy, C alkylthio, nitro, cyano, thiocyanato, G.4 alkylsulphonyl, halo(G.4)alkylsulphonyl, aminosulphonyl or CM alkoxycarbonyl, or naphthyl.
6. A compound according to any one of claims 1 to 3 in which R: 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, halo(G.4)alkyl, G. alkoxy, halo(G.4)alkoxy, nitro, cyano, phenyl, G-4 alkylsulphonyl or G.4 alkoxycarbonyl or, in the case of pyridyl, with 4 fluorine or chlorine atoms.
A compound according to any one of claims 1 to 3 in which R2 is 2-, 3- or 4- quinoiinyl, 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, G.4 alkyl, G.4 alkoxy or nitro and in its heterocyclic ring with halo. CM alkyl, halo(G.4)alkyl, G-4 alkoxy, halo(G. )alkoxy, nitro, cyano. G-4 alkylsulphonyl or G-4 alkoxycarbonyl.
A process for preparing a compound according to claim 1 which comprises the steps: (i) reacting a compound of formula (fl):
Figure imgf000040_0001
in which R1 has the meaning given in claim 1 and R is G.4 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 8, in a water-immiscible solvent in the presence of an acid catalyst.
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.
PCT/GB1997/000823 1996-04-15 1997-03-24 Substituted oxazolidinediones and their use as fungicides WO1997038997A1 (en)

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