GB1595698A - Triazole compound useful as a plant fungicide - Google Patents

Description

(54) TRIAZOLE COMPOUND USEFUL AS A PLANT FUNGICIDE (71) We, IMPERIAL CHEMICAL INDUSTRIES LIMITED, Imperial Chemical House, Millbank, London SWlP 3JF, British, do hereby declare the invention, for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- This invention relates to a 1,2,4-triazole compound having the properties of combating fungal diseases in plants.

The invention provides a compound which is 1 - t - butyl - 2 - (1,2,4 - triazol1 - yl) - 2 - (2',4' - dicblorobenzyl) - ethanol. The compound has a melting point of 140 143 C.

The compound of the invention contains chiral centres. The compound is generally obtained in the form of racemic mixtures. However these or other mixtures can be separated into the individual isomers by methods known in the art e.g. chromatography.

In many cases, the compound can be prepared stereospecifically in the form of a single diastereoisomer.

The compound can be prepared by reducing, preferably at 0 to 1000 C and for l to 12 hours, a compound of formula (I):

of a salt thereof. Suitable reducing agents are sodium borohydride, lithium aluminium hydride or aluminium isopropoxide. If desired, catalytic hydrogenation using a suitable metal catalyst can be used. Since the compound of general formula (I) is a sterically hindered ketone, a Grignard reagent, for example butylmagnesium halide (e.g. bromide or iodide) can be used as the reducing agent; when a reagent such as a butyl-magnesium halide is used, a single diastereoisomer can often be produced.

The reduction can be performed by dissolving the reactants in a solvent such as diethyl ether or tetrahydrofuran (for lithium aluminium hydride reduction) or hydroxylic solvents (for sodium borohydride reduction). The reaction temperature will depend on the reactants and solvent; but generally the reaction mixture is heated under reflux.

After the reaction, the product can be isolated by extraction into a convenient solvent after acidification with dilute mineral acid. On removal of the solvent in vacuo, the product may be crystallised from a convenient solvent.

The starting compound of formula (I) may be made by reacting 1,2,4-triazole, or a salt thereof, with a a-haloketone of general formula (II):

wherein X is halogen, preferably bromine or chlorine. This process may be carried out by heating the reactants together in the absence of a solvent or diluent, but preferably a solvent is present.

Suitable solvents are non-hydroxylic solvents such as acetonitrile, dimethylformamide, dimethyl sulfoxide, sulpholane and tetrahydroturan. Hydroxylatedisolvents, for example, methanol and ethanol, may be used in certain circumstances when the presence of the hydroxyl group does not interfere with the reaction. The process can be carried out in the presence of a base such as sodium hydride, sodium ethoxide, excess imidazole or triazole, or an alkali metal carbonate (e.g. potassium carbonate). The reaction temperature will depend upon the choice of reactants, solvents and base, but generally the reaction mixture is heated under reflux. The process generally consists of dissolving the reactants in a solvent and then isolating the product by removal of the reactant solvent in vacuo. Unreacted imidazole or triazole can be removed by extraction of the product with a suitable solvent which is then washed with water. A crystallisation or other purification procedure may then be carried out if desired.

The a-halo ketones, which may be made by known methods, are novel compounds.

They, and their analogues, are the subject of Patent Application No. 5534/80 (Serial No. 1,595,649).

The compounds of formula (I) or a salt thereof may also be made by benzylating a compound of formula (III):

Further details of this reaction can be found in British Patent Specification No.

1,533,706.

The compound is an active fungicide, particularly against the diseases: Piricularia oryzae on rice Pu cc in ia recondita, Puccinia striiformis and other rusts on wheat, Puccinia hordes Puccinia striiformis and other rusts on barley, and rusts on other hosts e.g. coffee, apples, vegetables and ornamental plants Erysiphe gram in is (powdery mildew) on barley and wheat and other powdery mildews on various hosts such as Sphaerotheca fuliginea on cactlrbits (e.g. cucumber), Podosphaera leucotricha on apples and Uncinula necator on vines Cercospora auachidicola on peanuts and other Cercospom species on for example sugar beet, bananas and soya beans Botrytis cinerea (grey mould) on tomatoes, strawberries, vines and other hosts Venturia inacqualis (scab) on apples The compound has also shown a broad range of activities against fungi in vitro.

It has activity against various post-harvest diseases on fruit (e.g. Penicillium digatatum and italicum on oranges and Gloeosporium musarum on bananas). Further the compound is active as seed dressings against: Fusarium spp., Septoria spp., Tilletia spp.

(i.e. bunt, a seed borne disease of wheat), Us tila go spp., and Pyrenophora spp. on cereals.

The compound can also be used as an industrial (as opposed to agricultural) fungicide, e.g. as paint film fungicides.

The compound also has plant growth regulating activities.

In carrying out the plant growth regulating method, the amount of compound to be applied to regulate the growth of plants will depend upon a number of factors, for example the identity of the plant species whose growth is to be regulated. However, in general an application rate of 0.1 to 15, preferably 0.1 to 5, kg per hectare is used.

However, on certain plants even application rates within these ranges may give undesired phytotoxic effects. Routine tests may be necessary to determine the best rate of application od the compound for any specific purpose for which it is suitable.

The compound may be used as such for fungicidal application but is more conveniently formulated into compositions for such usage. The fungicidal compositions comprise the compound of the invention and a carrier or diluent.

The compound can be applied in a number of ways, for example it can be formulated or unformulated, directly to the foliage of a plant, or it can be applied also to bushes and trees, to seeds or to other medium in which plants, bushes or trees are growing or are to be planted, or it can be sprayed on, dusted on or applied as a cream or paste formulation, or it can be applied as a vapour. Application can be to any part of the plant, bush or tree, for example to the foliage, stems, branches or roots, or to soil surrounding the roots, or to the seed before it is planted.

The term "plant" as used herein includes seedlings, bushes and trees. Furthermore, the fungicidal method includes preventative, protectant, prophylactic and eradicant treatment.

The compound is 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 dusting powders or granules comprising the active ingredient and a solid diluent or carrier, for example, kaolin, bentonite, kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia, Fuller's earth, gypsum, Hewitt's earth, diatomaceous earth and China clay. Compositions for dressing seed, for example, may comprise 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 or dimethylformamide).

The compositions may also be in the form of dispersible powders, granules or grains comprising a wetting agent to facilitate the dispersion in liquids of the powder or grains which may contain also fillers and suspending agents.

The aqueous dispersions or emulsions may be prepared by dissolving the active ingredient(s) in an organic solvent optionally containing wetting, dispersing or emulsifying agent(s) and then adding the mixture to water which may also contain wetting, dispersing or emulsifying agent(s). Suitable organic solvents are ethylene dichloride, isopropyl alcohol, propylene glycol, diacetone alcohol, toluene, kerosene, methylnaphthalene, the xylenes, trichloroethylene, furfuryl alcohol, tetrahydrofurfuryl alcohol, and glycol ethers (e.g. 2-ethoxyethanol and 2-butoxyethanol).

The compositions to be used as sprays may also be in the form of aerosols wherein the formulation is held in a container under pressure in the presence of a propellant, e.g. fluorotrichloromethane or dichlorodifluoromethane.

The compound 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 compound may be used in a microencapsulated form.

By including suitable additives, for example additives for improving the distribution, adhesive power and resistance to rain on treated surfaces, the different compositions can be better adapted for various utilities.

The compound can be used as mixtures with fertilisers (e.g. nitrogen-, potassium or phosphorus-containing fertilisers). Compositions comprising only granules of fertliser incorporating, for example coated with, the compound, are preferred. Such granules suitably contain up to 25% by weight of the compound.

The compositions may also be in the form of liquid preparations for use as dips or sprays which are generally aqueous dispersions or emulsions containing the active ingredient in the presence of one or more wetting agent(s), dispersing agent(s), emulsifying agent(s) or suspending agent(s). These agents can be cationic, anionic or nonionic 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 triisopropyl-naphthalene 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 nonyl-phenol and octylcresol. Other non-ionic agents are the partial esters derived from long chain fatty acids and hexitol anhydrides, the condensation products of the said partial esters with ethylene oxide, and the lecithins. Suitable suspending agents are hydrophilic colloids (for example polyvinylpyrrolidone and sodium carobxymethylcellulose), and the vegetable gums (for example gum acacia and gum tragacanth).

The 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 to be diluted with water before use. These concentrates often should 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 1085%, for example 2560%, by weight of the active ingredient. When diluted to form aqueous preparations, such preparations may contain varying amounts of the active ingredient depending upon the intended purpose, but an aqueous preparation containing 0.0005% or 0.01% to 10% by weight of active ingredient(s) may be used.

The compositions can comprise also other compound(s) having biological activity [e.g. growth stimulating substances such as the gibberellins (e.g. GAs, GA4 or GA7), the auxins (e.g. indoleacetic or indolebutyric acid) and the cytokinins (e.g. kinetin, diphenylurea, menzimidazole and benzyladenine) and other compounds having complementary fungicidal or insecticidal activity], as well as stabilising agent(s), for example epoxides (e.g. epichlorhydrin). The other fungicidal compound can be one which is capable of combating ear diseases of cereals (e.g. wheat) such as Septoria, Gibberella Helminthosporium and the sooty mould complex; examples of such compounds are benomyl, carbendazim (BCM) and captafol. Alternatively, it can be one which is capable of combating seed- and soil-borne diseases; examples of such compounds are maneb and captan.

The related compound, 1 - t - butyl - 2 - (1,2,4 - triazol - 1 - yl) - 2 - p - chlorobenzyl ethanol, is the subject of Patent Application No. 5524/80 (Serial No.

1,595,697). Analogues (and derivatives which are salts, ethers, esters and metal complexes) of this compound and of the compound of the present invention are the subject of Patent Application No. 34590/76 (Serial No. 1,595,696) which also claims processes for preparing both compounds and their derivatives and analogues, fungicidal compositions containing them and methods of using them.

The following Examples illustrate the invention; the temperatures are given in degrees Centigrade (").

EXAMPLE 1.

1 - t - Butyl - 2 - (1,2,4 - triazol - 1 - yl) - 2 - (2',4' - dichloro beryl) ethanol.

Stage 1. 1,2,4 - Triazole (33.4 g) and sodium ethoxide [from sodium (11.6 g) and ethanol (250 ml)] were refluxed for 1 hour. To this solution at the reflux temperature was added bromopinacolone (87 g), and heating was continued for a further 2 hours. The mixture was then cooled to ambient temperature, filtered to remove the precipitated sodium bromide and the solvent removed in vacuo. The residue was extracted with chloroform (100 ml). The solvent was washed with water (4 X 15 ml), dried (sodium sulphate) and filtered. Petroleum ether (b.p. 6080 ) was added and the solution concentrated to yield a - 1,2,4 - triazol - 4 - yl - pinacolone, m.p. 176".

Further concentration of the solution gave a - 1,2,4 - triazol - 1 - yl - pinacolone, m.p.

6365 .

Stage II. ze - (1,2,4 - triazol - 1 - yl) - pinacolone was converted into 1 (2',4' - dichlorophenyl) - 4,4' - dimethyl - 2 - (1,2,4-triazol - 1 - yl) - pentan - 3one using the techniques of Example 1 of Patent Application No. 34590/76. (Serial No. 1,595,696).

Stage III. 1 - (2',4' - Dichlorophenyl) - 4,4' - dimethyl - 2 - (1,2,4 - triazol1 - yl) - pentan - 3 - one (4.0 g) in methanol (40 ml) was treated with sodium borohydride (0.46 g). After initial exothermic reaction had subsided, the solution was refluxed on a steam bath for 1 hour. The solvent was removed in vacuo and 1Nhydrochloric acid (40 ml) was added to the residue to give a white crystalline solid, which was filtered off, washed with water and dried. Crystallisation from ethyl acetatepetroleum ether (60-,80O) gave 1 - t - butyl - 2 - (1,2,4 - triazol - 1 - yl) - 2 (2',4'-dichlorobenzyl)ethanol as a white crystalline solid, m.p. 140143 .

EXAMPLE 2.

The compound was 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 Seed, as appro priate) in 4 cm diameter minipots. A layer of fine sand was placed at the bottom of the pot to facilitate uptake of test compounds by the roots.

The test compounds were formulated either by bead-milling with aqueous Dis persol T ("Dispersol " is a Registered Trade Mark) or as a solution in acetone/ ethanol which was diluted to the required concentration immediately before use. For the foliage diseases, 100 p.p.m. a.l. suspensions were sprayed on to the foliage and applied to the roots of the same plant via the soil. (Sprays were applied to maximum retention, and root drenches to a final concentration equivalent to approximately 40 ppm a.i./dry soil). Tween 20 ("Tween" is a Registered Trade Mark), to give a final concentration of 0.1%, was added when the sprays were applied to the cereals.

For most of the tests, the test compound was applied to the soil (roots) and to the foliage (by spraying) one or two days before the plant was inoculated with the diseases. An exception was the test on Erysiphe graminis, in which the plants were inoculated 24 hours before treatment. After inoculation, the plants were put into an appropriate environment to allow infection to take place and then incubated until the disease was ready for assessment. The period between inoculation and assessment varied from 4 to 14 days according to the. disease and environment.

The disease control was recorded by the following grading: 4=No disease 3=0-5% 2=6-25 1=26-60% 0= > 60% The results are shown in Table I.

TABLE I DISEASE CONTROL

Puccinia Phytophthora Plasmopara Piricularia Botrytis Erysiphe recondita infestans viticola oryzae cgnerea graminis in wheat in tomato in vines in rice in tomato in barley 4 0 0-1 1 2-3 4 This compound is of interest because it has a weaker stunting effect on vegetative growth of monocotyledonous plants (e.g. wheat and barley) than the corresponding mono(chloro- or fluoro-) compounds.

EXAMPLE 3.

This Example illustrates the protectant activity (at 50 ppm) of the compound against various fruit fungal diseases.

The activity of the compound against apple powdery mildew (Podosphaera leucotricha) and vine powdery mildew (Uncinula necator) was determined as follows.

Small apple (Jonathan) and vine plants about 3 weeks old and growing in mini pots (diameter: 3 cm) were sprayed first with the solution or suspension of the test compound, allowed to dry overnight in a growth room and then infected on the following day with spores of the disease by placing them in an enclosed space and allowing spores of the disease blown into the still space to settle upon them over four to six hours.

Assessment was made of the percentage amount of disease on the leaves of the plants (after 8 days for apples and 9 to 10 days for vines).

The tests against apple scab (Venturia inaequalis) were performed as follows.

Ventuna inaequalis was treated as an obligate parasite, the spores of the fungus being transferred from plant to plant by-passing agar plate culture which ensures a very pathogenic fungus.

Infected leaves were removed from stock plants 13 days after inoculation. The spores were removed from the leaves by agitation in a small volume of deionised water, counted and then adjusted to 100,000 spores/ml. This suspension was sprayed onto the undersides of apple seedling leaves of one of three susceptible varieties, i.e.

Jonathan, Granny Smith and Red Delicious. The inoculated seedlings were iminedi- ately placed in a high humidity cabinet at 190 C and left therein for 48 hours. After this incubation period the plants were placed in growth room conducive to disease development. The disease was easily assessed 12 or 13 days after inoculation.

The test compound was applied 24 hours after inoculation.

The grading system used is the sarne as for Table I. Table II shows the results.

TABLE II

DISEASE CONTROL Podosphaera Uncinula Venturia leuchotricha necator inaequalis on apples on vines on apples 3 4 0-2 EXAMPLE 4.

The compound was tested at 50 ppm and as a protectant dip against Penicillium digitatum on oranges and Gloeosporium musarum on bananas, The oranges were scrubbed and then wiped over with industrial methylated spirit.

The peel was then removed and cut into discs with a No. 6 cork borer. The peel discs were then dipped into a solution (containing 0.1% Tween 20 as a wetting agent) of the test compound. They were then put outer side uppermost in Repli dishes. The discs were allowed to dry and were then sprayed with a spore suspension of Penicillium dgitatum at a concentration of 1 x 106 spores/ml. The dishes were then stored in a moist environment at 19 C for 13 days.

The tests on bananas were performed in a similar fashion using discs of banana peel.

The discs were then assessed using the grading system used for Table I. Table III shows the results.

TABLE III

DISEASE CONTROL P. digitatuni G. musarum on oranges on bananas 1 1

Claims (1)

1. WHAT WE CLAIM IS: 1 - t - Butyl - 2 - (1,2,4 - triazol - 1 - yl) - 2 - (2',4' - dichloro) - benzylethanol.