EP0371045A1

EP0371045A1 - Fungicidal compositions based on nicotine derivatives, new nicotine derivatives, and their preparation

Info

Publication number: EP0371045A1
Application number: EP88905894A
Authority: EP
Inventors: Claude Lambert; Régis Pepin
Original assignee: Rhone Poulenc Agrochimie SA
Current assignee: Bayer CropScience SA
Priority date: 1987-07-10
Filing date: 1988-06-30
Publication date: 1990-06-06
Also published as: FR2617844B1; JPH02504031A; DD285278A5; HUT54466A; IL86894A0; ES2010764A6; AU2071788A; BR8807610A; US4908375A; FR2617844A1; WO1989000568A1; GR880100452A; KR890701583A; ZA884943B; CN1030585A

Abstract

Dérivés nicotiniques. Ils sont de formule (I) avec: A = radical thiazolyl éventuellement illustré, Z = méthylène, m = 1 à 4, Y = H, hal, alcoyle (1-4C) alcoxy (1-4C), n = 1 à 3. Produits fongicides pour l'agriculture.Nicotine derivatives. They are of formula (I) with: A = thiazolyl radical optionally illustrated, Z = methylene, m = 1 to 4, Y = H, hal, (1-4C) alkyl (1-4C) alkoxy, n = 1 to 3 Fungicide products for agriculture.

Description

FUNGICIDAL COMPOSITIONS BASED ON NICOTINIC DERIVATIVES, NOVEL NICOTINIC DERIVATIVES AND THEIR PREPARATION

The present invention relates to fungicidal compositions based on nicotinic derivatives, novel nicotinic derivatives and the use of nicotinic derivatives for the control of fungal plant diseases, and in particular against rice blast. A more particular subject of the invention is fungicidal compositions characterized in that they contain, as active material, at least one compound of formula:

in which :

A is a thiazolyl radical of one of the formulas

in which R ₁ and R ₂ , which are identical or different, are:

. or a hydrogen atom. either a linear or branched alkyl or alkenyl radical of 1 to 18 carbon atoms, unsubstituted or substituted by a phenyl or phenoxy the phenyl ring of which can be substituted with one to five substituents chosen from the group comprising a halogen atom, an alkyl or alkoxy radical of 1 to 4 carbon atoms, . or a phenyl radical unsubstituted or substituted by one to five substituents chosen from the group comprising a halogen atom, an alkyl or alkoxy radical of 1 to 4 carbon atoms. either a pyridyl or thiofenyl radical

. either an amino group unsubstituted or substituted by at least one alkyl or alkoxy radical of 1 to 4 carbon atoms, pheny laminocarbonyl, alkyl or phenyl carbonyl in which the phenyl is unsubstituted or substituted by one to five substituents chosen from the group comprising a halogen atom, an alkyl or alkoxy of 1 to 4 carbon atoms.

- Z is an optionally substituted methylene radical

- m is an integer from 1 to 4, preferably 1 or 2. - Y is a halogen atom or an alkyl or alkoxy radical of 1 to 4 carbon atoms

- n is an integer from 0 to 3.

Preferred compounds have the formula I, in which A has the formula II, more particularly those in the formula in which R ₂ is an alkyl radical of 1 to 4 carbon atoms or a phenyl unsubstituted or substituted by 1 to 3 substituents chosen from the group comprising a chlorine atom, a methyl or ethyl radical, or methoxy or ethoxy.

The derivatives of formula I can be obtained according to several methods: first, the reaction of a compound of formula V with a suitable thiazoloalkyl halide can be carried out according to the scheme (Method A):

in which M is an alkali metal atom, X is a halogen atom and the other substituents have the same meaning as above.

The reaction is carried out in an aliphatic or aromatic solvent medium, for example optionally halogenated hydrocarbons (for example toluene), or amides, ketones, or nitriles (for example acetonitrile). Advantageously, the operation is carried out in the presence of a catalyst of the phase transfer catalyst type such as, for example, tris (dioxa-3,6 heptyl) amine (TDA-1) or crown ether 18-6.

It is also possible to react a compound of formula V with a chlorinating agent to give an acid chloride derivative VII which is reacted with an alcohol, according to the scheme (Method B):

Treatment of V with a chlorinating agent, such as phosgene, oxalyl chloride or thionyl chloride, in an aliphatic solvent such as a chloroalkane provides the derivative VII. This is transformed into compound 1 ppr reaction with the appropriate alcohol HO- (Z) _m A in the presence of organic base such as for example pyridine.

We can also perform a transesterification according to the scheme (Method C):

The reaction is carried out in an aromatic solvent such as for example toluene, in the presence of a catalytic amount of a base such as sodium methylate with distillation of the methanol-solvent azeotrope as the methanol is formed.

The following examples illustrate the preparation of the compounds according to the invention and their fungicidal properties. The structure of these compounds was verified by NMR spectrography.

EXAMPLE 1 Cyano-2 nicotinate

((2-methyl) 4-thiazolyl) methyl (method A) (compound 1) A mixture of 4.1g (0.022 mole) of potassium cyano-2 nicotinate, 2.95g (0.02 mole) of chloromethyl-4 2-methylthiazole, and 0.13 g (0.0005 mole) of crown ether 18-6 in 50 ml of acetonitrile is brought to reflux for 8 hours. The solvent is then evaporated, the residue taken up in water and extracted with dichl oromethane. After drying, evaporation of the dichloromethane and purification by chromatography on a silica column, 2.12 g (41%) of compound 1 are obtained (mp: 93 ° c) Example 2: Cyano-2 nicotinate

((3-chloro-2-phenyl) 4-thiazolyl methyl (method C) (compound 2) 0.11 g (0.002 mole) of sodium methylate are added to a solution of 3.24 (0.02 mole) of cyano- 2 methyl nicotinate and 4.96g (0.022 mole) of (3-chloro) 2-phenyl-4-hydroxy-methyl-thiazole in 100 ml of toluene. The methanol-toluene azeotrope is distilled, then the toluene is evaporated. The residue is treated with water. The precipitate formed is filtered, washed with water and then dried. We get 1.8g (25%) of compound 2 (mp = 130 ° C)

Example 3: By operating according to the procedures of Examples 1 or 2, the following compounds are obtained, the formula and the physico-chemical characteristics of which are given in the following table:

Example 4: The procedure of Example 2 is followed by replacing chloromethyl-4-methyl-2-thiazole with an equimolar amount of (chloro) -2-ethyl-5 methyl 4-thiazole. 5.5 g of a compound with a melting point of 88 ° C. are obtained, corresponding to 2-cyano-nicotinate of (methyl-4) 5-thiazolyl-2 ethyl.

Example 5: Greenhouse test, on Piricularia o ryzae Potted rice plants (Marcheti rosa variety) 10 cm high, are treated by watering the soil, with an aqueous suspension containing:

- 30 mg of the product to be tested

- 15 mg of a surfactant, ethylene oxide condensate (20 moles) on the sorbitan monoleate

- water qs 30 ml

This suspension, applied to 7 cm square pots, corresponds to a dose of approximately 60 kg / ha of active ingredient. The product is left to absorb by the soil. Part of the rice plants were not treated to serve as controls. After 24 hours after the treatment, all the rice plants are contaminated with a suspension of Pyricularia oryzae spores obtained by scraping off an in vitro culture, by spraying the leaves at the rate of 5 ml of suspension per pot. The pots are incubated for 48 h at 25 ° C under 100 ° relative humidity. The plants are then placed in a greenhouse observation cell

The observation is made after 8 days after contamination.

Under these conditions, it is observed that at the dose of 1000 ppm, an inhibition of at least 80% of the fungus is obtained with the compounds 1, 2 and 4.

This development clearly shows the systemic fungicidal properties of the compounds according to the invention and their remarkable action on the blast of rice. The products according to the invention can be used alone, dispersed or dissolved in water or in the form of compositions which can also contain all kinds of other ingredients such as, for example, protective colloids, adhesives, thickeners, of thixotropic agents, penetration agents, stabilizers, sequestrants, etc. as well as other known active materials with pesticide properties (notably insecticides or fungicides) or with properties promoting plant growth (especially fertilizers) or with properties regulators of plant growth. More generally, the compounds according to the invention can be combined with all the solid or liquid additives corresponding to the usual techniques of formulation.

These doses of use in the case of use as fungicides of the compounds according to the invention can vary within wide limits, in particular according to the virulence of the fungi and the climatic conditions. In general, compositions containing

0.5 to 5000 ppm of active substance are suitable; these values are indicated for the compositions ready for application. Ppm means "part per million". The zone from 0.5 to 5000 ppm corresponds to a zone from 5x10 ^-5 to 0.5% (percentages by weight).

As regards the compositions suitable for storage and transport, they more advantageously contain from 0.5 to 95% (by weight) of active substance. Thus, the compositions for agricultural use according to the invention can contain the active materials according to the invention within very wide limits, ranging from 5.10 ^-5 % to 95% (by weight).

According to what has already been said, the compounds according to the invention are generally associated with s uppo r t s and even t u l emen t s s agen t s tens i oac t i f s.

By the term "support", in the present description, is meant an organic or mineral, natural or synthetic material, with which the active material is associated to facilitate its application to the plant, to seeds or to the soil. This support is therefore generally inert and it must be acceptable in agriculture, especially on the treated plant. The support can be solid (clays, natural or synthetic silicates, silica, resins, waxes, solid fertilizers, etc.) or liquid (water, alcohols, ketones, petroleum fractions, aromatic or paraffinic hydrocarbons, chlorinated hydrocarbons, liquefied gases, etc.).

The surfactant can be an emulsifying, dispersing or wetting agent of ionic or nonionic type. Mention may be made, for example, of salts of polyacrylic acids, salts of lignosulfonic acids, salts of phenolsulfonic or naphthalene sulfonic acids, polycondensates of ethylene oxide on fatty alcohols or on fatty acids or on fatty amines , substituted phenols (especially alkylphenols or arylphenols), ester salts of sulfosuccinic acids, taurine derivatives (especially alkyltaurates), phosphoric esters of polyoxyethylated alcohols or phenols. The presence of at least one surfactant is generally essential when the active material and / or the inert support are not soluble in water and the vector agent for the application is water.

The compositions used in the invention can be in fairly diverse forms, solid or liquid. As forms of solid compositions, mention may be made of dusting powders (with an active ingredient content of up to 100%).

As forms of liquid compositions or intended to constitute liquid compositions during application, mention may be made of solutions, in particular water-soluble concentrates, emulsifiable concentrates, emulsions, concentrated suspensions, aerosols, powders wettable (or spraying powder), granules, pastes. Emulsifiable or soluble concentrates most often comprise 10 to 80% of active material, emulsions or solutions ready for application containing, for their part, 0.001 to 20% of active material. In addition to the active ingredient and the solvent, the emulsifiable concentrates can contain, when necessary, a suitable co-solvent and from 2 to 20% of suitable additives, such as stabilizers, surfactants, in particular emulsifiers, penetrating agents, corrosion inhibitors, dyes, adhesives. Example (CE 1) - active ingredients (400 g / l

- dodecy Ibenzene alkali sulfonate 24 g / l

- oxyethylated nonylphenol containing 10 molecules of ethylene oxide 16 g / l

- cyclohexanone 200 g / l - aromatic solvent q.s.p 1 liter

According to another concentric formula, very emulsifiable, we use:

Example (CE 2)

- active ingredients ( 250 g / l - epoxidized vegetable oil 25 g / l

- mixture of alkylaryl sulfonate and polyglycol ether and fatty alcohol 100 g / l

- dimethhtlformamide 50 g / l

- xylene q.s.p 1 1 575 g / l From these concentrates, emulsions of any desired concentration can be obtained by dilution with water, which are particularly suitable for application to grading.

The concentrated suspensions, also applicable in spraying, are prepared so as to obtain a stable fluid product which does not deposit and they usually contain from 10 to 75% of active material, from 0.5 to 15% of surfactants, from 0 , 1 to 10% of thixotropic agents, from 0 to 10% of suitable additives, such as defoamers, corrosion inhibitors, stabilizers, penetrating agents and adhesives and, as support, water or an organic liquid in which the active ingredient is little or not soluble: certain organic solids or mineral salts can be dissolved in the support to help prevent sedimentation or as antifreezes for water .

By way of example, here is the composition of several aqueous suspensions according to the invention: Example SP 1:

An aqueous suspension is prepared comprising: - active material (compound No. 1) ................................. 500 g / l

- wetting agent (polyethoxylated C ₁₃ synthetic alcohol) ....................................... .................................... 10 g / l

- dispersing agent (salified ethoxylated polyaryl phenol phosphate) ....................................... ............................... 50 g / l - antifreeze (propylene glycol) .......... ......................................... 100 g / l

- thickener (polysaccharide) .......................................... 1.6 g / l

- biocide (4-methylhydroxy benzoate) .... 3.3 g / l

- water ................................................ .................................... OSPl liter.

A concentrated fluid suspension is thus obtained. Example SP 2 - Aqueous suspension:

An aqueous suspension is prepared comprising: -active material (compound 2) ................................... ..... 100 g / l

- wetting agent (polyethoxylated alkylphenol .. 5 g / l

- dispersing agent (Naphthalene sulfonate Na 10 g / l - antifreeze (Propylene glycol) ................................. ................. 100 g / l

- thickener (Polysacharide) ............................................. ..3 g / l

- biocide (Formaldehyde) ............................................. ................ 1 g / l

- water ................................................ .................................... QSPl liter.

Example SP 3 - Aqueous suspension: An aqueous suspension is prepared comprising:

- active ingredient (compound nº 4) ....................................... 250 g / I

- wetting agent (polyethoxylated synthetic C ₁₃ alcohol ........................................ ...................................... 10 g / l

- dispersing agent (solium lignosulfonate) 15 g / I - antifreeze (urea .................................. ............................................. 50 g / l

- thickener (Polysacharide ........................................... 2,5 g / l - biocide (Formaidehyde) ............................................. ................ 1 g / l - water ............................ .............................................. QSPl liter.

Wettable powders (or spray powder) are usually prepared so that they contain 20 to 95% of active ingredient, and they usually contain, in addition to the solid support, 0 to 5% of a wetting agent, 3 to 10% of a dispersing agent, and, when necessary, from 0 to 10% of one or more stabilizers and / or other additives, such as penetrating agents, adhesives, or anti-caking agents, coloring agents , etc.

As an example, here is the composition of several wettable powders. Example PM 1, wettable powder - active material (compound 1 according to the invention) 50%

- ethoxylated fatty alcohol (wetting agent) .......................... 2.5%

- ethoxylated styrylphenol (dispersing agent) .............. 5%

- chalk (inert support) ............................................ .................. 42.5%

Example PM 2: 10% wettable powder - active ingredient (compound 4) ................................ ............. 10%

- synthetic branched type oxo alcohol, C ₁₃ ethoxylated with 8 to 10 ethylene oxide (wetting agent) .......................... .................................................. ................ 0.75%

- neutral calcium lignosulfonate (dispersing agent ........................................ .................................................. ................. 12%

- calcium carbonate (inert filler) ..................... qs 100% Example PM 3: 75% wettable powder containing the same ingredients as in the example above, in the following proportions: - active ingredient (compound n ° 2) ................................ ................. 75%

- wetting agent ............................................... ............................... 1.50%

- dispersing agent ............................................... ................................... 8%

- calcium carbonate (inert filler) ..................... qs 100% Example PM 4: 90% wettable powder

- active ingredient (compound n ° 1) ......................................... ...... 90%

- ethoxylated fatty alcohol (wetting agent ................................ 4%

- ethoxylated styrylphenol (dispersing agent) ........ 6% Example PM 5: 50% wettable powder

- active material (compound n ° 4 according to the invention) .. 50%

- mixture of anionic and nonionic surfactants (wetting agent) 2.5%

- neutral sodium lignosulfonate (dispersing agent) ....................................... .................................................. ................. 5%

- kaolin clay (inert support) ................................... 42.5%

To obtain these sprayable powders or wettable powders, the active material is intimately mixed in appropriate mixers with the additional substances and ground with mills or other suitable grinders. This gives sprayable powders whose wettability and suspension are advantageous; they can be suspended with water at any desired concentration and this suspension can be used very advantageously in particular for application to the leaves of plants.

The compounds according to the invention can advantageously be formulated in the form of water-dispersible granules also included within the scope of the invention.

These dispersible granules, of apparent density generally comprised between approximately 0.3 and 0.6, have a particle size generally comprised between approximately 150 and 2000 and preferably between 300 and 1500 microns. The content of active material (compound No. 4) of these granules is generally between approximately 1% and 90%, and preferably between 25% and 90%.

The rest of the granule is essentially composed of a solid filler and optionally surfactant additives giving the granule properties of dispersibility in water. These granules can be essentially of two distinct types depending on whether the charge selected is soluble or not in water. When the filler is water-soluble, it can be mineral and preferably organic. Excellent results have been obtained with urea. In the case of an insoluble filler, it is preferably mineral, such as kao lin or bentonite. It is then accompanied by surfactants (at a rate of 2 to 20% by weight of the granule), surfactant adjuvants of which more than half is constituted by at least one dispersing agent, essentially anionic, such as a poly (alkaline or alkaline earth naphthalene sulfonate) or an alkaline or alkaline earth lignosulfonate, the remainder consisting of nonionic or anionic wetting agents such as an alkali or alkaline earth alkyl naphthalene sulfonate. Furthermore, although this is not essential, other adjuvants can be added such as anti-foaming agents.

The granule according to the invention can be prepared by mixing the necessary ingredients and then granulation according to several techniques known per se (bezel, fluid bed, atomizer, extrusion, etc.). It generally ends with a crushing followed by sieving to the particle size chosen within the limits mentioned above. Preferably, it is obtained by extrusion, operating as indicated in the examples below. Example GD I: Dispersible granules containing 90% active material

In a mixer, 90% by weight of active material (compound No. 2) and 10% urea pearls are mixed. The mixture is then ground in a pin mill. A powder is obtained which is moistened with approximately 8% by weight of water. The wet powder is extruded in a perforated roller extruder. A granule is obtained which is dried, then crushed and sieved, so as to keep respectively only the granules of a size included between 150 and 2000 microns.

Example GD 2; Dispersible granules with 75% active ingredient

In a mixer, the following constituents are mixed:

- active ingredient (compound n ° 1) ............................ 75%

- wetting agent (sodium alkylnaphthalene sulfonate .......................................... .............................. 2%

- dispersing agent (sodium polynaphthalene sulfonate) ......................................... .......................... 8%

- inert filler insoluble in water (kaolin) ............ 15%

This mixture is granulated in a fluid bed, in the presence of water, then dried, crushed and sieved so as to obtain granules of size between 0.16 and 0.40 mm. These granules can be used alone, in solution or dispersion in water so as to obtain the desired dose. They can also be used to prepare combinations with other active materials, in particular fungicides, the latter being in the form of wettable powders, or aqueous granules or suspensions. As has already been said, aqueous dispersions and emulsions, for example compositions obtained by diluting with water a wettable powder or an emulsifiable concentrate according to the invention, are included in the general scope of the compositions which can be used in the present invention. The emulsions can be of the water-in-oil or oil-in-water type and they can have a thick consistency like that of a "mayonnaise".

This process is characterized in that it consists in applying to these plants an effective amount of a composition containing as active material a compound according to formula (I). By "effective amount" means an amount sufficient to allow the control and destruction of the fungi present on these plants. The doses of use can however vary within wide limits according to the fungus to fight, the type of culture, climatic conditions, and depending on the compound used.

In practice, doses ranging from 1 g / hl to 500 g / hl corresponding substantially to doses of active material per hectare from 10 g / ha to approximately 5000 g / ha generally give good results.

Claims

1) Nicotine derivatives of formula

(I)

in which :

- A is a thiazolyl radical of one of the formulas:

in which R ₁ and R ₂ , which are identical or different, are:

. either a hydrogen atom,

. either a linear or branched alkyl or alkenyl radical of 1 to 18 carbon atoms, unsubstituted or substituted by a phenyl or phenoxy the phenyl ring of which can be substituted by one to five substituents chosen from the group comprising a halogen atom, an alkyl or alkoxy radical of 1 to 4 carbon atoms,

. either a phenyl radical unsubstituted or substituted by one to five substituents chosen from the group comprising a halogen atom, an alkyl or alkoxy radical of 1 to 4 carbon atoms,

. either a pyridyl or thiofenyl radical,

. either an amino group unsubstituted or substituted by at least one alkyl or alkoxy radical of 1 to 4 carbon atoms, phenylaminocarbonyl, alkyl- or phenyl carbonyl in which the phenyl is unsubstituted or substituted by a with five substituents chosen from the group comprising a halogen atom, an alkyl or alkoxy of 1 to 4 carbon atoms,

- Z is an optionally substituted methylene radical, - n is an integer from 1 to 4, preferably 1 or 2,

- Y is a halogen atom or an alkyl or alkoxy radical of 1 to 4 carbon atoms,

- n is an integer from 0 to 3.

2) Derivatives according to claim 1 characterized in that A has the formula II.

3) Derivatives according to claim 2 characterized in that n is equal to 1 or 2.

4) Derivatives according to claim 3 characterized in that R ₂ is an alkyl radical of 1 to 4 carbon atoms. 5) Derivatives according to claim 4 characterized in that R ₂ is methyl.

6) Derivatives according to claim 5 characterized in that R ₂ is a phenyl substituted with 1 to 3 substituents chosen from the group comprising a chlorine atom, a methyl or ethyl radical, a methoxy or ethoxy radical.

7) Process for manufacturing compounds according to one of claims 1 to 6 of formula

(I)

in which A, Υ, Z, m and n have the same meanings as in claim 1, characterized in that an alkaline salt of cyanonicotinic acid of the formula (v)

in which Y _n has the same meaning as above and M is characterized as an alkali metal with a halide hal- (Z) _m A in which A and m have the same meanings as above and hal represents a halogen atom. 8) Process for the preparation of compounds according to one of claims 1 to 6, characterized in that a methyl cyano-2 nicotinate is reacted with an alcohol in a solvent medium, in particular aromatic, in the presence of a catalytic amount of an alcoholate according to the scheme:

j

with azeotropic distillation of methanol as it is formed.

9) Process for preparing the compounds according to claim 1, characterized in that a compound of formula II is reacted with a chlorinating agent to give an acid chloride derivative III which is reacted with an alcohol according to the scheme: at)

in a solvent, in particular an aliphatic solvent b) The compound of formula III is reacted with the appropriate alcohol in the presence of an organic base such as pyridine, according to the scheme:

10) Fungicidal compositions for the protection of plants against fungal diseases characterized in that they contain as active material a compound according to one of claims 1 to 6.

11) A method of treating fungal diseases of plants, characterized in that a compound according to one of claims 1 to 6 is used as active material.