CS208150B2 - Method of preparation of the triazoles and imidazoles - Google Patents

Description

The invention relates to a process for the preparation of heterocyclic compounds, in particular imidazoles and 1,2,4-triazoles, which are useful as fungicides and plant growth regulators.

The present invention provides a process for the preparation of triazoles and imidazoles of the general formula I

H OH

where

Y is = N- or = CH-

R 1 is C 1-4 alkenyl or benzyl optionally substituted by halo, trifluoromethyl, nitro, cyano, C _1-4 alkyl, C _1-4 alkoxy, O, 4 alkylenedioxy amino, hydroxy, phenyl or phenoxy groups and / or optionally substituted phenyl or alkyl on the alpha carbon atom,

R 8 is propyl or butyl; and er

R 1 is methyl or C 8 -C 4 alkenyl and its acid addition salts, characterized in that the compound of formula II

208,50

Η

where

R, R 1 and R 8 are as defined above, or an acid addition salt thereof is reacted at 15 to 80 ° C with a compound of the general formula

RjMgX wherein Rj is as defined above and

X is halogen.

The compounds of the invention contain chiral centers. Usually, the compounds of the invention are obtained in the form of racemic mixtures. However, these or other mixtures can be separated into the individual isomers by methods known per se, for example by chromatography. In many cases, the compounds can be prepared stereospecifically as one diastereoisomer.

The benzyl group may contain more than one substituent in the ring. Examples of polysubstituted groups include groups containing up to as many substituents as possible (especially containing 1, 2 or 3 substituents), such as halogen atoms, especially chlorine atoms and / or nitro-, methyl- or methoxy groups.

Suitable salts are those with inorganic or organic acids, for example hydrochloric, nitric, sulfuric, toluenesulfonic, acetic or oxalic acids.

Specific examples of compounds of the invention are shown in Table 1.

Table ,

Number »1 r ₂ ^r 3 Y Melting point or boiling point (° C) 1 pfc ₆ h ₄ ch ₁ - terc.Bu Me = N- 152 to 153 2 p-ci-c ₆ h ₄ ch ₂ terč.Bu Me = N- 176 to 78 3 2-Cl-4-F-C ₈ H ₃ CH ₂ terč.Bu Me = N- 53 to 154 4 ofc ₆ h ₂ ch ₂ target. Bu Me = CH- , 46-149 5 p-Br-C ₈ H ₄ CH ₂ terc.Bu Me = CH- 188 to 92

The reaction underlying the process of the invention can be carried out by methods known per se.

The starting compound of formula II can be prepared by reacting imidazole or 1,2,4-triazole or a salt thereof with an alpha-haloketone of formula III

208,50

R ₂ <! - CH-X (III)

I «1 where

X is halogen, preferably bromo or chloro and

R 1 and R ₂ ^{have the} meanings given above.

The process may be carried out by heating the reactants together, optionally in the presence of a solvent or diluent. Preferably, the reaction is carried out in the presence of a solvent.

Suitable solvents are those without hydroxyl groups such as acetonitrile, dimethylformamide, dimethylsulfoxide, sulfolane and tetrahydrofuran. Solvents containing hydroxy groups such as methanol and ethanol may be used under certain conditions as long as the presence of the hydroxy groups 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 depends on the choice of reagents, solvents and base, but usually the reaction mixture is heated to reflux.

Usually, in the process, the reactants are first dissolved in a solvent and the product is isolated after the reaction has been completed by vacuum removal of the reaction solvent. Unreacted imidazole or triazole can be removed by extraction of the product with a suitable solvent, which is then washed with water. If desired, crystallization or other purification may then optionally be performed.

The alpha-haloketones can be prepared by known methods.

Compounds of formula II or salts thereof may also be prepared by alkenylation, alkynylation or aralkylation of a compound of formula IV

where

Y and R ₂ have the above meanings.

Further details of this reaction can be found in German Patent Application Publication No. 2 6.0 022.

The compounds are effective fungicides, in particular against the following diseases:

Piricularia oryzae on rice,

Puccinia recondita, Puccinia striiformis and other rust on wheat,

Puccinia hordei, Puccinia striiformis and other rust on barley and rust on other host plants such as coffee, apple, vegetables and ornamental plants,

Plasmopara viticola on vines,

Erysiphe graminis (powdery mildew) on barley and wheat and other powdery mildew on various host plants, such as Sphaerotheca fuliginea on cucumbers, Podosphaera leucotricha on apple trees and Uncinula necator on vines,

208150 4

Cercospora arachidicola on groundnuts and other species of Cercospora on banana and soybean diabetes,

Botrytis cinerea (gray mold) on tomatoes, strawberry, grapevine and other host plants,

Phytophthora infestans (potato late blight) on tomatoes' a

Venturia inaequalis (scab) on apple trees.

Some of the compounds of the invention also have a wide range of activity against fungi in vitro. They have an effect against various fruit diseases occurring on fruit after harvest (for example Penicillium digatatum and Fenicillium italicum on oranges, Oloeosporium musarum on bananas. Some of the compounds are effective as seed dressings against Fusarium spp., Tilletia spp. (Seed-borne wheat disease). , Ustilago spp., And Fyrenophora spp. On cereals.

The compounds of the invention may also be used as industrial (as opposed to agricultural) fungicides, for example as fungicides in paints.

The compounds of the invention also have an effect on plant growth regulation.

The effect of compounds on plant growth control is manifested, for example, as an effect of stunting the vegetative growth of monocotyledons or dicotyledons. Such stunting can be useful, for example, in cereals or soy, where shortening the stem can reduce the risk of lodging. Growth stunting compounds may also be useful in the fictional mode of sugarcane growth, as they increase the sugar concentration in the cane at harvest. Achieving stunting at groundnuts can help the harvest. Grass growth retardation can help maintain grass turf.

Examples of suitable grasses include Stenotaphrum secundatum, Cynosurus cristatus, Lolium multiflorum and Lolium perenne, Agrostis tenuis, Cynodon dactylon, Dactylia glomerata, Festuca spp. (for example Festuca rubra) and Poa spp. (e.g., Poa pratense). At least some of the compounds of the invention have an effect on grass stunting without significant phytotoxic effect and without detrimentally affecting the appearance (e.g. grass color), making them attractive for use in maintaining ornamental lawns and grassy edges of beds etc. The compounds can also stun weeds present in these grasses, such as Cyperus spp. and dicotyledonous weed plants. The compounds of the invention can also be used to retard the growth of non-cultivated vegetation, for example, weed plants or natural plant coverings, which can be used to maintain plantations or salts. Regulatory effect on plants may be manifested by increased crop yield.

Other regulatory effects of the compounds on plant growth include changing the angle of the leaves of the plants and promoting the offshoot of monocotyledons. Changing the angle of the leaves may be useful, for example, in the case of a change in the orientation of the leaves in potatoes, which allows more light to reach the cultivated plants, resulting in increased photosynthesis and tuber weight. Increasing the offshoot of monocotyledonous crops (e.g. rice) can increase the flowering shoot per unit area, resulting in an increase in the total grain yield of these crops. Treatment of plants with the compounds of the invention may result in the color of the leaves of the plants having a darker green tint.

The compounds of the invention may also inhibit the flowering of diabetes, which results in an increase in sugar yield. They can also reduce the size of the sugar lumps without significantly reducing the sugar yield, which makes it possible to increase the sowing density.

In regulating plant growth by the compounds of the invention, the amount of compound used depends on a number of factors, for example the particular compound selected and the species of plant to be controlled. In general, however, 0.1 to 15, preferably 0.1 to 5 kg of compound per hectare is applied. However, in certain plants, application within this range may also have an undesirable phytotoxic effect. Conventional assays may be necessary to determine the optimum amount of a specific compound for each specific purpose for which the use of the compound is appropriate.

The compounds of the invention also have an algicidal, antibacterial and antiviral effect and a herbicidal effect.

Compounds per se may be used to control fungi or to control plant growth, but are conveniently used in the form of compositions. The compositions comprise a compound of Formula I, or a salt thereof, and a carrier or diluent.

The compounds of formula (I) and salts thereof may be used to control fungicidal plant diseases and to control plant growth by applying to a plant, plant seed or a place where the plant or seed is located a compound of the invention or a salt thereof as defined above.

The compounds of the formula I and their salts can be applied in various ways, for example they can be applied as such or in the form of compositions, either directly to the leaves of plants or directly to the bushes and trees or seeds or to the environment in which the plants, bushes or the trees grow or are to be grown. The compounds or compositions can be applied as sprays, dusts or creams or pastes or can be applied in the form of vapors. They can be applied to any part of the plant, shrub or tree, for example to leaves, stems, branches or roots or to the soil surrounding the roots or to the seeds before sowing.

The term plant refers to both seedlings and shrubs and trees. The fungicidal effect of the invention is preventive, protective, prophylactic or uprooting.

The compound of the invention is preferably used in the form of compositions for agricultural and horticultural purposes. The type of composition used will always depend on the particular intended purpose.

The compositions may take the form of dusts or granules containing the active ingredient and a solid diluent or carrier such as kaolin, bentonite, diatomaceous earth, dolomite, calcium carbonate, talc, magnesium oxide powder, fuller's earth, gypsum, Hewitt's clay, diatomaceous earth and kaolin. The seed dressing compositions may contain, for example, a seed adhesion promoter (e.g., mineral oil). Alternatively, the active ingredient may be formulated into a seed dressing composition with an organic solvent (e.g., N-methylpyrrolidone or dimethylformamide).

The compositions may also take the form of dispersible powders, granules or grains containing a surfactant to facilitate dispersion of the powder or grains in liquids. These compositions may also contain fillers and suspending agents.

Aqueous dispersions or emulsions can also be prepared by dissolving the active ingredient (s) in an organic solvent optionally containing one or more wetting, dispersing or emulsifying agents and then adding water optionally containing wetting, dispersing or emulsifying agents to the mixture. Suitable organic solvents are ethylene dichloride, isopropyl alcohol, propylene glycol, diacetone alcohol, toluene, kerosene, methylnaphthalene, xylenes, trichlorethylene, 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 in which the composition is maintained in a container under pressure in the presence of a propellant, for example fluorotrichloromethane or difluorodichloromethane.

The compounds may also be mixed with the pyrotechnic mixture in the dry state to form smoke-containing compositions containing the compounds in confined spaces.

Alternatively, the compounds may be used in the form of microcapsules (in microencapsulated form).

By varying the application, the various compositions can be better adapted by adding suitable additives, for example additives to improve the distribution, adhesion or rain resistance of the compounds on the treated surfaces.

The compounds may be used in the form of mixtures with fertilizers (for example, fertilizers containing nitrogen, potassium or phosphorus). Preference is given to those compositions which contain only fertilizer granules into which it is introduced, for example by coating the compound of the invention. Such granules suitably contain up to 25% by weight of the compound.

The compositions may also take the form of liquid preparations, which are used as a dipping bath or spray. Such compositions are generally aqueous dispersions or emulsions containing the active ingredient in the presence of one or more wetting, dispersing, emulsifying or suspending agents. These agents may be cationic, anionic or nonionic agents. Suitable cationic agents are quaternary ammonium compounds, for example oethyltrimethylammonium bromide.

Suitable anionic agents are soaps, salts of aliphatic monoesters of sulfuric acid (e.g. sodium lauryl sulfate) and salts of sulfonated aromatic compounds (e.g. sodium dodecylbenzenesulfonate, sodium, calcium or ammonium lignosulfonate, corresponding butylnaphthalenesulfonate and a mixture of diisopropyl and triisopropylnaphthalenesulfonate).

Suitable non-ionic agents are the condensation products of ethylene oxide with fatty alcohols such as oelyl or cetyl alcohol, or 8 alkylphenols such as octyl or nonylphenol and octyl cresol. Other nonionic agents include partial esters derived from long chain fatty acids and hexite anhydrides, the condensation products of these partial esters with ethylene oxide and lecithins. Suitable suspending agents are hydrophilic colloids (e.g., polyvinylpyrrolidone and sodium carboxymethyl cellulose) and resins of vegetable origin (e.g., gum arabic and tragacanth).

Compositions intended for use in the form of aqueous dispersions or emulsions are generally supplied in the form of concentrates containing a high proportion of the active compound or compounds, and the concentrate is then diluted with water before use. These concentrates often withstand long-term storage and, after such storage, can be diluted with water to form aqueous compositions which are homogeneous for a period of time sufficient to be applied by conventional spray equipment. The concentrates suitably contain up to 95%, preferably 10 to 25%, for example 25 to 60% by weight of the active ingredient (s). When diluted with water to aqueous compositions, the resulting compositions may contain varying amounts of active ingredient or ingredients, depending on the intended use. Typically, however, aqueous compositions containing 0.0005 or 0.01 to 10% by weight of the active ingredient (s) are used.

The compositions of the invention may also contain other compounds having a biological effect (e.g. other growth stimulating agents such as gibberellins (e.g., GA 1, GA 2 or βΑγ)), auxins (e.g. indole acetic or indole butyric acid) and cytokinins (e.g. kinetin, diphenylurea, benzimidazole and benzyladenine) and other compounds with complementary fungicidal or insecticidal activity and stabilizers, for example epoxy compounds (for example epichlorohydrin) As other fungicidal compounds, a compound which is capable of controlling ear diseases in cereals, for example wheat such as Septoria, Giberella, Helminthsporum and Examples of such compounds include benomyl, carbendazole (BCM) and captafol.

Alternatively, the compound may be a compound that is capable of controlling seed or soil-borne diseases. Examples of such compounds include Maneb and Captan.

The following examples serve to illustrate the invention in more detail. The temperature is given in ° C.

Products labeled with company names in the examples have the following structure:

Tween 20: a condensate surfactant based on sorbitan monolaurate with ethylene oxide

Aerosol OT: sodium dioctylsulfosuccinate

Polyphon H: sodium lignin sulphonate

Dispersol T: a mixture of sodium sulphate and formaldehyde condensate with sodium naphthalenesulphonic acid.

Example 1

1- (1,2,4-triazol-1-yl) -1-p-fluorobenzyl-2-tert-butylpropan-2-ol (Compound 1)

An ethereal solution of methylmagnesium iodide (prepared by the reaction of methyl iodide (6.2 g) with magnesium (1.1 g) in dry diethyl ether) was treated dropwise with alpha-1,2,4-triazol-1-yl-alpha-p-fluorobenzylpinacolone (4.0 g) in dry diethyl ether (30 mL). The mixture was then refluxed for 1 hour, cooled and treated with 10% sulfuric acid (20 mL). The insoluble material is filtered off, washed with dilute hydrochloric acid and water and then dried. Crystallization from aqueous ethanol gave the title compound.

Example 2

In this example, several compositions of the invention are listed.

1. Dispersible powder

2. Emulsifiable concentrate compound 1 aerosol OT Polyphon H kaolin% by weight 2% by weight 5% by weight compound 1 100 g / liter amine dodecylbenzenesulfonate 400 g / liter 2-n-butoxyethanol up to 1 liter

3. Aqueous Suspension

4. Dust Compound 1 Polyphon H bentonite polysaccharide water

250 g / liter 25 g / liter, 5

0.75 to 1 liter of compound 1 kaolin 95% by weight

5. Granulate

6. Compound 1 solvent solution 5% starch 5% kaolin 90% compound 1 dimethylformamide

200 g / liter to 1 liter

Example 3

The compounds are tested against various plant foliar diseases. This testing technique is used.

The plants are grown in John Innes pot compost (No. 1 or Seed as needed) in 4 cm diameter mini pots. A fine sand layer is placed at the bottom of the pots to facilitate uptake of the test compound by the roots.

The test compounds are formulated either by grinding in a ball mill with aqueous Dispersol T or dissolved in acetone / ethanol and diluted to the desired concentration just prior to use. In foliar diseases, a 100 ppm active ingredient suspension is sprayed onto the leaves and the suspension is introduced through the soil to the roots of the same plant. (Spraying is applied to the maximum containment and root dressing to a final concentration of about 40 ppm of active ingredient based on dry soil.) Before applying the spray to cereals, Tween 20 is added to the formulation to a final concentration of 0.1%.

In most tests, the test compound is applied to soil (roots) and leaves (by spraying) one or two days before inoculation of plants with diseases. The exception is the test and Erysiphe graminis, in which the plants are inoculated 24 hours before treatment. After inoculation, the plants are placed in a suitable environment which allows the infection to break out and then incubated until the disease can be evaluated. The period between inoculation and evaluation varies from 4 to 14 days depending on the disease and the environment.

Disease control is characterized by the following steps = no disease 3 = 0 to 5% = 6 to 25% = 26 to 60% = more than 60%.

The results are shown in Table 2.

Table 2

Slou- chenina number Disease control Puccinia recondita on wheat Phytophthora infestane on tomatoes Flasmopara viticola on vine Piricularia oryzae on genuine Cercospora arachidicola on groundnut Botrytis cinerea on tomatoes Erysiphe graminis on barley 1 4 0 0 3 0 4 2 2 0 3 0 1 to 2 4 3 1 to 2 2 to 3 0 0 1 to 2 3 4 0 to 1 0 to 1 0 3 4 to 3 5 0 to 3 0 0 3 to 4 4 to 3

Example 4

This example illustrates the protective effect of compounds (at 50 ppm) against various fruit diseases.

The activity of the compounds against powdery mildew (Podosphaera leucotrieha) and powdery mildew (Uncinula necator) is determined. The tests are as follows:

Small plants of apple tree (Jonathan) and vines about 3 weeks old grown in small pots of 3 cm diameter are first sprayed with a solution or suspension of the test compound, allowed to dry overnight in a greenhouse, and infected by spores of the disease the following day. the plants are placed in an enclosed space and the disease spores inflated into this space are allowed to settle on the plants for 4 to 6 hours without flow.

Percent infection of plant leaves with disease is carried out in apple trees after 8 days and in vine plants after 9 to 10 days.

In addition, the activity of the compounds against apple scab (Venturia inaequalis) is tested. These tests shall be carried out as follows:

The spores of Venturia inaequalis, as an obligate parasite, are transferred from plant to plant using an agar culture that provides a highly pathogenic fungus.

Infected leaves are removed from the stock infested plants 13 days prior to inoculation. Spores are removed from the leaves by mixing in a small volume of deionized water, counted and then adjusted to 100,000 spores / ml. The suspension is sprayed onto the lower leaves of the apple seedlings of one of three susceptible species, i.e. Jonathan, Granny Smith and Red Delicious. The inoculated seedlings were immediately placed in a high humidity and 19 ° C room and left there for 48 hours. After this incubation period, the plants are placed in a growth area where disease is allowed to develop. The disease is easily evaluated 12 or 3 days after incubation.

The test compound is administered 24 hours after incubation.

The same assessment system as in Table 2 is used. The results are shown in Table 3.

Table 3

Compound number Disease control Podosphaera leuchotricha on apple trees Uncinued the necator on the vine Venturia inaequalis on apple trees 1 0 4 2 0 2 3 1 0 0

Example 5

This example illustrates the regulatory effect of compounds on plant growth. The compounds are applied as a solution in 5,000 ppm distilled water and applied to the leaves of young seedlings of wheat, barley, corn, rice, ryegrass, soybean, cotton208150 Ku, groundnuts, lettuce, tomatoes, golden beans and beans common. The experiments are repeated twice. 21 days post-treatment, plants are evaluated for their regulatory effect on growth and phytotoxic symptoms.

Table 4 shows the effect of compounds on stunting of vegetative plant growth. This classification system is used.

= á 20% retardation = 21 to 40% retardation = 41 to 60% retardation = 61 to 80% retardation

If no number is given, the compound is substantially ineffective as an agent for achieving stunted growth.

Other plant growth control properties are identified as follows:

G = darker green leaf color,

A = peak effect,

T = offshoot effect.

The symbol indicates that the compound has not been used in crop testing.

An asterisk (+) indicates that the compound is administered at a concentration of 4000 ppm.

Table 4 (0 ti • Ti ti

Φ> three

Φ ϋ

• H

XQ ti.

> O

Φ

Ό

O

XSJ

1?

Φ

H

O

Φ

O

Φ

N

Ό

O

Q.

tíi (0

H

N o

N ce tí

Φ

O

O ta

Λ

2GA 1

2GA 2A

A 0 IA

A 2G

Claims (3)

. OBJECT OF THE INVENTION Process for the preparation of triazoles and imidazoles of the general formula I H OH II (i) where Y is = N- or = CH- R represents a C ₂ -4 alkenyl or benzyl optionally ring-substituted by halogen, trifluoromethyl, nitro, kysno-, C, _ alkyl, alkoxy, alkylendioxy-, amino, hydroxy, phenyl or phenoxy and / or and optionally substituted phenyl or alkyl on the alpha carbon atom, R ₂ is propyl or butyl; R represents methyl or C ₂ -C 4 alkenyl group, and their acid addition salts, wherein a compound of formula II wherein Y, R 1, and R ₂ are as defined above, or an acid addition salt thereof is reacted at 15 to 80 ° C with a compound of formula R ₃ MgX where R ₃ is as defined above and X is halogen. 2. Method of claim 1 for the preparation of compounds of formula I wherein R is methyl and Y, R and R ₂ have the meanings given in point 1, characterized in that as compounds of formula II used is a compound in which Y has the meaning R @ 1 is a benzyl group optionally substituted by halo, alkyl-, nitro-, trifluoromethyl-, cyano-, alkoxy- or (C1-4 alkylene) dioxo and / or optionally on the alpha-carbon atom substituted by one phenyl or C 1-4 alkyl; and R ₂ is as defined in point 1, or a salt thereof, and as a compound of formula R 1 MgX methyl magnesium halide. 3. Process according to claim 1 for preparing compounds of formula I wherein R is methyl and Y, R, and R ₂ have the meanings given in point 1, characterized in that as compounds of formula II used is a compound in which Y has the meaning referred to in point 1, R, is benzyl optionally substituted by halo, C 1-4 alkyl-, nitro-, trifluoromethyl-, cyano-, alkoxy- or (C 1-6 alkylenedioxy) groups and / or optionally substituted at alpha- and R ₂ is as defined in point 1, or a salt thereof, and as a compound of formula R 1, X 1, methylmagnesium halide.