Halogensubstituted derivatives of benzimidazole and their acid - salt additive, intermediate compounds and fungicidal agent

 

(57) Abstract:

The invention relates to new halogensubstituted the benzimidazole of the formula I, in which R1, R2, R3and R4mean hydrogen, halogen, alkoxy with 1 to 4 carbon atoms, a group of the formula Z - R5where R5means unsubstituted phenyl, pyridinyl which can be substituted by trifluoromethyl, and Z denotes oxygen, sulfur; R2and R3together signify unsubstituted or substituted alkylenes chain with 3 or 4 links, in which two (non-adjacent) carbon atoms may be replaced by oxygen atom; A denotes a group of the formula: - SO2- R6or

,

where Y represents oxygen or sulfur; R6, R7, R8independently of one another denote alkyl with 1 to 4 carbon atoms, alkoxy with 1 to 4 carbon atoms, alkenyl with 1 to 4 carbon atoms, dialkylamino, phenyl which may be substituted by nitro, stands, trifluoromethyl; 1-pyrrolidinyl, 1-piperidinyl; or thienyl, pyrazolyl, isoxazolyl, each of these residues can be substituted by chlorine, amine, stands, methoxy, trifluoromethyl, methoxycarbonyl; X represents halogen, and their acid additive salt. The new compounds possess fungicidal activity, thanks Bretania. It is also an object of the invention is a new intermediate compounds of formulas IIa and IVa to obtain compounds of the formula I, in which R9, R10, R11and R12independently of one another denote hydrogen, haloalkylthio or R10, R11together with the carbon atoms to which they are linked, form at least once substituted by halogen 5 - and 6-membered heterocyclic ring with one or two (nesoedinimoe) oxygen atoms and X is halogen, R13and R14mean hydrogen, haloalkylthio. 4 C. and 3 h.p. f-crystals, 3 tables.

The present invention relates to new biologically active benzimidazole, more particularly to a halogen-substituted derivatives of benzimidazole and their acid additive salts, intermediate compounds and fungicidal tool.

Known benzimidazole derivatives having biological activity, for example fungicidal activity (see application EP N 0517476 A2, class C 07 D 491/056, 09.12.1992).

Object of the invention is the expansion of the range of benzimidazole having biological activity, in particular fungicidal activity.

The problem is solved by the proposed methods derived halogenase what each other mean a hydrogen, halogen, nitro, alkoxy with 1-4 carbon atoms, a group of the formula

Z-R5,

where R5means unsubstituted phenyl, pyridinyl which can be substituted by trifluoromethyl, and Z denotes oxygen, sulfur;

R2and R3means unsubstituted or substituted akilanova chain with 3 or 4 links, in which two (messenia) carbon atoms may be replaced by oxygen atom,

A denotes a group of the formula: -SO2-R6or

,

where Y represents oxygen or sulfur; and

R6, R7, R8independently of one another denote alkyl with 1-4 carbon atoms, alkoxy with 1-4 carbon atoms, alkenyl with 1-4 carbon atoms, dialkylamino, phenyl which can be substituted one to three times nitro, stands, trifluoromethyl; 1-pyrrolidinyl, 1-piperidinyl; or thienyl, pyrazolyl, isoxazolyl, each of these residues can be substituted one to three times by chlorine, amine, stands, methoxy, trifluoromethyl, methoxycarbonyl;

X represents halogen,

and their acid additive salts.

The acids that may be attached, are preferably kaleidotrope acid, such as hydrochloric and Hydrobromic acid, in particular chloride is hydroxycarbonate acid, for example acetic acid, maleic acid, succinic acid, fumaric acid, tartaric acid, citric acid, salicylic acid, sorbic acid and lactic acid, and sulfonic acids, for example p-toluensulfonate, 1,5-naphthalenedisulfonate and, in addition, saccharin and tishrin.

Preferred halogen-substituted derivatives of benzimidazole of the formula (I) are compounds in which R1, R2, R3and R4independently of one another denote hydrogen, fluorine, chlorine, bromine, iodine, a group of the formula

Z-R5,

where R5and Z have the above meaning,

R2and R3together signify unsubstituted or substituted from one to six times by halogen, alkyl with 1-4 carbon atoms and/or haloalkyl with 1-4 carbon atoms and 1-9 halogen atoms alkylenes chain with 3 or 4 members in which one or two (messenia) carbon atom may be replaced by oxygen atom,

X represents fluorine, chlorine, bromine or iodine,

A denotes a group of the formula-SO2-R6or

,

where Y denotes oxygen or sulfur, and

R6, R7, R8have the above meaning.

Particularly preferred halogen-substituted derivatives of the aircraft is bromo, and A group of the formula

,

or R1and R4mean hydrogen, R2and R3together mean a group of-O-CF2-O-, X is chlorine and A is a group of the formula

< / BR>
Halogensubstituted derivatives of benzimidazole of the formula (I) and their acid additive salts can be obtained by reacting benzimidazole derivatives of the formula (II)

< / BR>
in which R1, R2, R3, R4and X have the above values,

with halides of the formula (III)

A-X1(III)

in which A has the above meaning, and

X1means halogen,

optionally, in the presence of acid binding means and, if necessary, in the presence of a diluent,

and to the resulting compounds of the formula (I), if necessary, added acid.

The halides of formula (III) are known or can be obtained by known methods.

As a diluent when carrying out this method is used by all conventional inert organic solvents. Preferred are aliphatic, alicyclic or aromatic hydrocarbons, for example petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; Dan, dichloroethane or trichloroethane; next, ethers, such as diethyl ether, diisopropyl ether, methyl-tert.-butyl ether, methyl-tert.-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; in addition, ketones, such as acetone, butanone, methyl-isobutylketone or cyclohexanone; next, NITRILES, for example acetonitrile, propionitrile, n - or ISO-butyronitrile or benzonitrile, or amides, such as N,N-dimethylformamide, N,N-dimethylacetamide, N-methylformamide, N is an organic or triamide hexamethylphosphoric acid, and esters, for example methyl or ethyl ester of acetic acid, and sulfoxidov, such as dimethylsulfoxide, and sulfones, such as sulfolane.

As acid binding means you can use all customary inorganic or organic bases. Preferably used hydrides of alkali or alkaline earth metals, hydroxide, amide, alcoholate, acetate, carbonate or bicarbonate, for example sodium hydride, sodium amide, sodium methylate, sodium ethylate, tert.-butyl potassium, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, sodium carbonate, potassium carbonate, bikebuilder, N,N-dimethylaniline, N,N-dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, N,N-dimethylaminopyridine, diazabicyclo, Diisobutylene or databaseconnect.

The reaction temperature can vary in a wide interval. Typically operate at temperatures from 0oC to 150oC, preferably from 20oC to 120oC.

1 mol benzimidazole derivative of the formula (II) used is usually from 1 to 15 mol, preferably 1-2 mol, in particular 1-1,3 mol, of a halide of formula (III).

The reaction is carried out usually under normal pressure. However, you can also work at elevated or reduced pressure, typically from 0.1 to 10 bar.

The reprocessing of the reaction mixture is carried out by conventional methods.

Salts of compounds of formula (I) with acids get a simple way by conventional methods, for example by dissolving the compounds of formula (I) in a suitable inert solvent and adding the acid, for example hydrochloric acid and was isolated in a known manner, for example by filtration, and optionally purified by washing inert organic solvent.

If you use 2-chloro-1H-benzimidazole and toluene-4-sulphonylchloride, the process protece the water benzimidazole of General formula (II) partially known.

Are new benzimidazole derivatives of the formula (IIA)

< / BR>
in which R9, R10, R11and R12independently of one another denote hydrogen, haloalkylthio, or R10, R11together with the carbon atoms to which they are linked, form at least once substituted by halogen 5 - or 6-membered heterocyclic ring with one or two (nesoedinimoe) atoms of oxygen, and

X represents halogen.

These compounds are an additional object of the invention.

Derivatives of benzimidazole of the formula (IIA) are obtained by interaction

a) benzimidazole of the formula (IV)

< / BR>
where R9, R10, R11and R12have the above values,

with calodromini means, optionally in the presence of a diluent and optionally in the presence of acid binding means,

or

b) bromobenzimidazole formula (IIB)

< / BR>
where R9, R10, R11and R12have the above values,

with hydrofluoric, hydrochloric or idiscovered acid or its salt of the formula (V)

M+X2-(V)

where M means the equivalent of a metal or Quaternary ammonium ion, catstye diluent.

If you use the 5-triptoreline-1H-benzimidazole and N-bromosuccinimide, the process according to the method of (a) proceeds according to the scheme 2 (listed at the end of the description).

As halogenation means using elemental chlorine or N-halogenide as N-bromosuccinimide or N-chlorosuccinimide.

As a diluent for use with all conventional inert organic solvents. Preferred are aliphatic, alicyclic or aromatic hydrocarbons, for example petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; next, halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane, next, ethers, such as diethyl ether, diisopropyl ether, methyl-tert.-butyl ether, methyl-tert. -amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; next, NITRILES, for example acetonitrile, propionitrile, n-or ISO-butyronitrile or benzonitrile, or amides, such as N, N-dimethylformamide, N,N-dimethylacetamide, N-methylformamide, N is an organic or triamide hexamethylphosphoric acid.

As acid binding is Auda alkaline earth hydrides or alkali metals, their hydroxides, amides, alcoholate, acetates, carbonates or bicarbonates, for example sodium hydride, sodium amide, sodium methylate, sodium ethylate, tert.-butyl potassium, sodium hydroxide, potassium hydroxide, ammonium hydroxide, sodium acetate, potassium acetate, calcium acetate, sodium carbonate, potassium carbonate, potassium bicarbonate, ammonium acetate or ammonium carbonate, or tertiary amines, such as trimethylamine, triethylamine, tributylamine, N,N-dimethylaniline, N,N-dimethylbenzylamine, pyridine, N-methylpiperidine, N-methylmorpholine, N, N-dimethylaminopyridine, diazabicyclo, Diisobutylene or databaseconnect.

The reaction temperature can vary in a wide interval. Typically operate at temperatures from -20oC to +120oC, preferably from 0oC to 80oC.

During the process are usually at atmospheric pressure, however it is possible to work at elevated pressure, or if you are not using gaseous components, and also under reduced pressure.

1 mol of a benzimidazole of the formula (IV), usually an equivalent amount or an excess halogenous funds. Processing of the reaction mixture is carried out by conventional methods.

New are the benzimidazole Faure is kiltia.

Data connection is a further object of the invention.

The benzimidazole of the formula (IV) produced by interaction of phenylendiamine formula (VI)

< / BR>
where R13and R14have the above values,

with formic acid, with one of its salts or one of its derivatives, such as formamide, trimethylamin ether orthomorphisms acid, dialkylimidazolium, formamidines, s-triazine or carbon monoxide, optionally in the presence of a diluent, such as water, methanol, ethanol or methoxyethanol, at a temperature of from 0oC to 180oC, preferably from 20oC to 150oC.

If you use a 4-triptoreline-o-phenylenediamine and formic acid, the process proceeds according to the scheme 3 (listed at the end of the description).

Phenylendiamine formula (VI) is known.

If you use 2-bromo-5-triptoreline-1H-benzimidazole and sodium chloride, the process according to the method (b) proceeds according to the scheme 4 (listed at the end of the description).

The compounds of formula (IIB) can be obtained from the above method (a).

Necessary for carrying out the method (b) fluorine-, chlorine - and idiscovered acids are widely the Noah metal, in particular lithium, sodium or potassium, or Quaternary ammonium ion, sulfone, sulfoxide or phosphonium, preferably tetraalkylammonium, with 1-12 carbon atoms in the alkyl chain and X2means fluorine, chlorine, or iodine.

Salt of the formula (V) are known compounds used in various syntheses.

As a diluent when carrying out process (b) use all customary inert organic solvents. Preferred are aliphatic, alicyclic or aromatic hydrocarbons, for example petroleum ether, hexane, heptane, cyclohexane, methylcyclohexane, benzene, toluene, xylene or decalin; next, halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane or trichloroethane; next, ethers, such as diethyl ether, diisopropyl ether, methyl tert. -butyl ether, methyl-tert.-amyl ether, dioxane, tetrahydrofuran, 1,2-dimethoxyethane, 1,2-diethoxyethane or anisole; in addition, ketones, such as acetone, butanone, methyl-isobutylketone or cyclohexanone; next, NITRILES, for example acetonitrile, propionitrile, n - or ISO-butyronitrile or benzonitrile, or amides, such as N,N-dimethylfuran the esters, for example methyl or ethyl ester of acetic acid, and sulfoxidov, such as dimethyl sulfoxide and sulfones, such as sulfolane. If necessary it is possible to carry out the interaction in the two-phase system, for example in a mixture of toluene with water.

The reaction temperatures when carrying out process (b) can vary within a wide interval. Typically operate at temperatures from -20oC and +150oC, preferably from 0oC to 120oC.

1 mol of bromobenzimidazole usually take an equivalent amount or an excess of the corresponding reaction component. Processing of the reaction mixture is carried out by conventional methods.

As mentioned above, halogen-substituted derivatives of benzimidazole of the formula (I) possess fungicidal activity, so that they represent the active substance fungicidal agent, which is another object of the present invention. The proposed remedy containing more standard additives target includes an active ingredient in an effective amount.

Good tolerance of plants active compounds, when necessary to combat fungal diseases of plants concentrations allows for the processing of land use to combat fungal diseases in fruit and vegetable production, for example, against Venturia, or for combating fungal diseases of crops, such as species of Erysiphe, Cochliobolus, Pyrenophora, or plants, or for combating diseases of rice, for example, against the causative agent of spots on rice (Pyricularia).

In the protection of materials the compounds according to the invention is used for protection of technical materials against the destruction of unwanted fungi and caused their destruction.

Under the technical materials see materials intended for use in the technique. Such technical materials, protected from microbicide alteration or destruction, are, for example, adhesives, glues, paper and cardboard, textiles, leather, wood, masonry paints and plastics and other materials that may be damaged by microorganisms or to collapse them. Under be protected materials also understand parts of industrial installations, for example, for circulation of cooling water, which may adversely impact due to the growth of microorganisms. In the framework of the present invention as technical materials preferably should be called adhesives, glues, paper and cardboard, leather, wood, painting, chill the ical properties can be translated in the usual formulation, for example solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, nonconception in polymeric substances form.

These compounds get in a known manner, for example by mixing the active substances with extenders or liquid solvents, pressurized gases and/or carriers, optionally with the use of surface-active agents, i.e. emulsifiers and/or dispersants and/or foam. In the case of using water as a filler can also be used as an aid in organic solvents. As liquid solvents are mainly used aromatic hydrocarbons, such as xylene, toluene or alkylnaphthalenes, chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzene, chloroethylene or methylene chloride, aliphatic hydrocarbons such as cyclohexane or paraffins, for example petroleum fractions, alcohols, such as butanol or glycol and also their ethers and esters, ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, highly polar solvents such as dimethylformamide and dimethylsulfoxide, and water. P is mperature and normal pressure are gaseous, such as working gases for aerosols, such as butane, propane, nitrogen and carbon dioxide. As solid carriers use the grinding of natural rocks such as kaolin, alumina, talc, chalk, quartz, montmorillonite or diatomaceous earth, and the grinding of synthetic rocks, such as highly dispersed silicic acid, alumina and silicates. As solid carriers for granules are used crushed and fractionated natural rocks such as calcite, marble, pumice, thick, dolomite, and also synthetic granules of inorganic and organic grinding, and also granules of organic material such as sawdust, coconut husk, corn cobs and stalks of tobacco. As emulsifying and foaming means is used, for example, nonionic and anionic emulsifiers, such as esters of polyoxyethylene and fatty acids, ethers of polyoxyethylene and fatty alcohols, for example alkylarylsulphonates simple ether, alkyl sulphonates, alkyl sulphates, arylsulfonate and protein hydrolysates. As a dispersant is used, for example, ligninolytic liquor and methylcellulose.

The compositions can also be used connecting aimery, for example gum Arabic, polyvinyl alcohol, polyvinyl acetate, and also natural phospholipids, such as Catalina and lecithins, and synthetic phospholipids. Other additives can be mineral and vegetable oils.

You can also use colorants such as inorganic pigments, for example iron oxide, titanium oxide, ferrocyanide blue, and organic dyestuffs, such as alizarin, azo and metallophthalocyanine dyes, and trace elements in the form of salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc.

The compositions usually contain from 0.1 to 95 wt.% the active substance, preferably from 0.5 to 90%.

The activity and spectrum of activity of active substances can be improved by adding other antibacterial active compounds, fungicides, bactericides, herbicides, insecticides, growth regulators, fertilizers or other active ingredients to increase the spectrum of action or achieve a particular effect, such as additional protection against insects. These compounds can have a broader spectrum of activity than the compounds according to the invention.

A mixture of active substances preferably contain the active substance in a concentration of 0.1 to 99.9%, especially predmosti additives.

The active substance can be applied as such, in the form of compounds or in the form of cooked of these forms for applications, such as ready-to-use solutions, emulsifiable concentrates, emulsions, foams, suspensions, powders for spraying, pastes, soluble powders, preparations for dusting and pellets. The application in the normal way, for example by watering, spraying, spreading, spraying, smearing, etc. is Also possible to apply the active substance ultrascalable method or composition with active early or very active substance incorporated into the soil. You can also process the seed.

When processing parts of plants the concentration of the active substance in a form ready for use, vary in a wide interval: usually, they range from 1 to 0.0001 wt.%, preferably from 0.5 to 0.001 wt.%.

When the seed treatment, the amount of active substance is usually from 0.001 to 50 g per kg of seed, preferably from 0.01 to 10 g

During cultivation, the concentration of active substance in the applications is from 0.00001 to 0.1 wt.%, preferably from 0.0001 to 0.02 wt.%.

Used for protection of technical materials among the walkie-talkie in the application of substances depends on the type and origin of the microorganisms, and on the composition of the protected material. The optimal number is determined by a number of experiments. Usually the concentration of application range from 0.001 to 5 wt.%, preferably from 0.05 wt.% to 1.0 wt.%, counting on the protected material.

Deriving halogen-substituted benzimidazole of the formula (I) is illustrated by the following examples.

Example 1

< / BR>
Method (a)

A mixture of 1.4 g (5 mmol) of 2-bromo-6,6-debtor-[1,3]dioxolo[4,5-f]benzimidazole and 30 ml of absolute tetrahydrofuran is mixed at room temperature and mixed with 0.2 g (5 mmol) of sodium hydride (60%) and then stirred for 30 minutes at room temperature. Then add 1.0 g (5.5 mmol) of 3,5-dimethylisoxazol-4-sulphonylchloride and stirred for 3 hours at room temperature. To handle pour the reaction mixture into 100 ml of water. The resulting mixture was twice extracted with 50 ml ethyl acetate. The combined organic phases are dried over sodium sulfate and concentrated under reduced pressure. The obtained residue chromatographic on silica gel using methylene chloride as the eluting means. Thus obtained 1.2 g (75% of theory) of 1-(3,5-dimethylisoxazol-4-sulfonyl)-2 - bromo-6,6-debtor-[1,3] dioxolo[4,5-f]benzimidazole in the Method (a)

To a suspension of of 0.48 g (12 mmol) of 60% sodium hydride in 20 ml of absolute dimethylformamide was added 2.0 g (10 mmol) of 6,6-debtor-[1,3]dioxolo[4,5-f] benzimidazole, stirred for 30 minutes at 20oC, was added 2.2 g (12 mmol) of N-bromosuccinimide and stirred for further 30 minutes at the same temperature. The mixture was poured onto 250 g of ice, establish glacial acetic acid to pH 4 and extracted three times 100 ml of ethyl acetate. The combined organic extracts dried over sodium sulfate and concentrated in vacuum. The resulting residue is stirred with 50 ml of water and the precipitate is filtered off and dried it. Obtain 2.3 g (83% of theory) of 2-bromo-6,6-debtor-[1,3] dioxolo[4,5-f]benzimidazole in the form of a solid substance with so pl. 160-164oC.

< / BR>
Method (b)

To 37.6 g (0.2 mol) of 5,6-diamino-2,2-diferential add 80 ml of 98% formic acid and heated 4 hours at the boil under reflux. After cooling alkalinized 2 N. sodium alkali. The precipitate is filtered off, washed with 200 ml of water and dried. Get to 38.1 g (95% of theory) of 6.6-debtor[1,3]dioxolo[4,5-f]benzimidazole in the form of a solid substance.

Analogously to example 1 are shown in table 1 connection.

Example 36

< / BR>
The way (the hydrogen chloride for 2 hours at 120oC. the Mixture was poured onto 250 g of ice, extracted three times 80 ml of ethyl acetate. The combined organic extracts dried over sodium sulfate and concentrated under reduced pressure. The remainder chromatographic on silica gel. Get 0.5 r (21.5% of theory) of 2-chloro-6,6-debtor-[1,3]dioxolo[4,5-f]benzimidazole in the form of a solid substance with so pl. >220oC.

Example 37

< / BR>
2-bromo-6,6,7,7-titrator-[1,4] like[2,3-f] benzimidazole get described in example 1 method.

So pl.: 170-174oC

Example 38

< / BR>
2-chloro-[1,4] -like-[2,4-f] benzimidazole get described in example 1 method.

So pl.: 150oC

Example 39

< / BR>
6,6,7,7-titrator-[1,4] like[2,3-f] benzimidazole get described in example 1 method.

So pl.: 70-74oC

The fungicidal activity of the compounds of formula (I) is illustrated by the following examples.

Example 40

Test the protective activity against Phytophthora on tomatoes

1 weight. some of the listed in table 2 of the active substance is mixed with 4.7 weight. including acetone as solvent and 0.3 weight. including alkylarylsulphonates ether as an emulsifier and dilute the concentrate with water to the concentrations specified in table 2.

eh. After drying plaque plants inoculant aqueous spore suspension of Phytophthora infestans and leave in the incubation chamber at 20oC and 100% relative humidity.

Later, 3 days after inoculation estimate. 0% means the degree of activity, which corresponds to the control, and the degree of activity of 100% means that there was no destruction.

The results of the experiments are presented in table 2.

Similar results are obtained when using other active substances, summarized in table 1.

Example 41

Test the protective activity against Plasmopara in the vine

1 weight. some of the listed in table 3, the active substance is mixed with 4.7 weight. including acetone as solvent and 0.3 weight. including alkylarylsulphonates ether as an emulsifier and dilute the concentrate with water to the concentration listed in table 3.

To test for protective activity, young plants are sprayed with the active composition to the formation of droplets. After drying plaque plants inoculant aqueous spore suspension Plasmopara viticola and leave it in a humid chamber for one day at 20-22oC and 100% relative humidity.

Later, 6 days after inoculation estimate. 0% means the degree of activity, which corresponds to the control, and the degree of activity of 100% means that there was no destruction.

The results of the experiments are presented in table 3.

Example 42

Test the protective activity against Venturia on Apple trees

1 weight. part of the active substance of example 3 is mixed with 4.7 weight. including acetone as solvent and 0.3 weight. including alkylarylsulphonates ether as an emulsifier and dilute the concentrate with water to a concentration of 100/h/mill.

To test for protective activity, young plants are sprayed with the active composition to the formation of droplets. After drying plaque plants inoculant aqueous spore suspension of the pathogen of Apple scab Venturia inaequalis and leave in the incubation chamber for one day at 20oC and 100% relative humidity.

Then the plants are placed in a greenhouse at 20oC and a relative humidity of about 70%.

After 12 days after inoculation estimate. 0% means the degree of activity, which corresponds to the control, and the degree of activity of 100% means that have not been observed, nikakogo benzimidazole of the formula I

< / BR>
in which R1, R2, R3and R4independently of one another denote hydrogen, halogen, alkoxy with 1-4 carbon atoms, a group of the formula

Z-R5,

where R5means unsubstituted phenyl, pyridinyl which can be substituted by trifluoromethyl, and Z denotes oxygen, sulfur;

R2and R3means unsubstituted or substituted akilanova chain with 3 or 4 links, in which two (messenia) carbon atoms may be replaced by oxygen atom;

A represents a group of the formula

-SO2-R6< / BR>
or

< / BR>
where Y represents oxygen or sulfur;

R6, R7, R8independently of one another denote alkyl with 1-4 carbon atoms, alkoxy with 1-4 carbon atoms, alkenyl with 1-4 carbon atoms, dialkylamino, phenyl which can be substituted one to three times nitro, stands, trifluoromethyl; 1-pyrrolidinyl, 1-piperidinyl or thienyl, pyrazolyl, isoxazolyl, each of these residues can be substituted one to three times by chlorine, amine, stands, methoxy, trifluoromethyl, methoxycarbonyl;

X means halogen,

and their acid additive salt.

2. Halogensubstituted derivatives of benzimidazole of the formula I on p. 1, Kotor is the formula

Z-R5,

where R5and Z are specified in paragraph (1 value;

R2and R3together signify unsubstituted or substituted from one to six times by halogen, alkyl with 1-4 carbon atoms and/or haloalkyl with 1-4 carbon atoms and 1-9 halogen atoms alkylenes chain with 3 or 4 members in which one or two (messenia) carbon atom may be replaced by oxygen atom;

X is fluorine, chlorine, bromine or iodine;

A represents a group of the formula

-SO2-R6< / BR>
or

< / BR>
where Y represents oxygen or sulfur;

R6, R7, R8are specified in paragraph (1 value.

3. Derived halogen-substituted benzimidazole of formula I under item 1, in which R1and R4mean hydrogen, R2and R3together mean a group of-O-CF2-O-, X is bromine, a group of the formula

< / BR>
4. Halogensubstituted derivatives of benzimidazole of formula I under item 1, in which R1and R4mean hydrogen, R2and R3together mean a group of-O-CF2-O-, X is chlorine, a group of the formula

< / BR>
5. Halogensubstituted derivatives of benzimidazole of the formula IIa

< / BR>
in which R9, R10, R11and R12independently of one another denote hydrogen, haloalkylthio substituted by halogen 5 - or 6-membered heterocyclic ring with one or two (nesoedinimoe) atoms of oxygen;

X means halogen,

as a starting compound to obtain a halogen-substituted derivatives of benzimidazole of the formula I on PP.1-4.

6. The benzimidazole of the formula IVa

< / BR>
in which R13means hydrogen, haloalkylthio;

R14means hydrogen, haloalkylthio,

as a starting compound to obtain a halogen-substituted derivatives of benzimidazole under item 5.

7. Fungicidal agent containing the active substance and the target additives, characterized in that the active substance it contains a derivative halogen-substituted benzimidazole of formula I under item 1 or an acid additive salt in an effective amount.

Priority points:

10.08.1995 - PP.1, 5 - 7;

08.03.1996 - PP.1 and 2.

 

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in which A represents an optionally substituted benzene ring, naphthalene ring or benzene ring condensed with the lowest alkylenedioxy; ring B represents an optionally substituted benzene, Y = -N= CR or CR=N-

The invention relates to new derivatives of 4.1-benzoxazepin-2-she is of the formula (I), where R1lower alkyl, substituted by at least one optionally substituted hydroxyl group, R2and R3independently of one another is hydrogen or phenyl, which is substituted by 1-3 substituents selected from the group consisting of lower C1-C4alkoxygroup; X is a bond, methylene group or a linking group with a chain length of 1-7 atoms, selected from the group consisting of -(CH2)m-E-(CHR6)n-, where m and n = 1 or 2 independently from each other: E-bond or an oxygen atom, -NR5-, -CONR7-, where R5-methylsulphonyl, R6and R7independently of one another(i) hydrogen, (ii) lower alkyl, which is not substituted or substituted by substituents selected from the group consisting of piperidine, indolyl, possibly esterified carboxypropyl, (iii) benzyl, Y is optionally substituted carbarnoyl and/or the substituents on the N atom of carbamoyl, taken together, form a ring which may be substituted, or tetrazolyl, or piperidine, and the ring And is substituted by 1-3 substituents selected from the group consisting of atoms of Halogens or their salts

The invention relates to an improved process for the preparation of substituted indole derivatives useful in the treatment and prevention of migraine

The invention relates to a derivative of oxazolidin-2-it General formula (I):

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where X is O,

Y denotesor

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R1indicatesor< / BR>
R2and R3each, independently of one another, denotes H, A or benzyl;

A denotes alkyl with 1-6 C-atoms;

D denotes amidinopropane, aminomethyl, aminohydrocinnamic, 5-methyl-1,2,4-oxadiazolidine-3-yl or guanidinate;

r and s independently of one another denote 0, 1, 2, 3 or 4;

however, if necessary, free amino - or amidinopropane can be protected partially or fully protective for the amino function groups, as well as their enantiomers, diastereomers and physiologically acceptable salts

The invention relates to new derivatives of benzylpiperidine formula I, where R1denotes H or Hal, R2is unsubstituted or substituted Gal in the aromatic ring of the benzyl group in the 2 -, 3-or 4-position piperidino ring, provided that R2doesn't mean 4-benzyl when X represents-CO-, Y -, and Z represent CH2and R1- N; R3denotes H or A , X IS-CO-, Y is --CH2-, -NH - or-O-, Z is-CH2- or connection, And - alkyl WITH1-6In - OH, H+, HE, Hal Is F, Cl, Br or I, and their salts

The invention relates to new derivatives of benzimidazole and their salts formed by the addition of acids, the way they are received and microbicide tool based on them

The invention relates to novel triazole compounds of the General formula (1), where a denotes a linear or branched C1-C18-alkylenes group which may comprise at least one group which is selected from O, S, CONH, COO,3-C6-cycloalkene or double or triple bond; In denotes the radical of formula (a), (b) or (C); R1denotes H, NH2WITH3-C6-cycloalkyl or1-C8-alkyl, which is not substituted or substituted OS1-C8-alkyl; R2denotes H, HE, C1-C8-alkyl, C3-6-cycloalkyl, CF3, CN, NR3R4, SR3or CO2R3where R3denotes N or C1-C8-alkyl, a R4denotes H, C1-C8-alkyl, or COR3where R3stands WITH1-C8-alkyl; Ar represents naphthyl, phenyl with 1-2 substituent selected from C1-C8-alkyl, CF3, CHF2, NO2, SR3, SO2R3where R3means1-C8-alkyl; and pyridyl, pyrimidyl or triazinyl, which have from 1 to 3 substituents selected from C1-C8-alkyl, C2-C6-alkenyl, C2-C6-quinil, halogen, CN, CF3, OR4where R43-C6-lalouche possibly condensed, phenylalkylamine or 5-membered aromatic heterocycle with 1 to 2 nitrogen atoms, which may be condensed with a benzene ring

The invention relates to arylalkylamines formula I, where In - unsubstituted pyridyl, pyrazinyl, isoxazolyl or thienyl; Q - CH2; X - CH2or S; R1and R2each - H; and R3- OR5; R4OA; R5- Or cycloalkyl with 4-6 C atoms; And the alkyl with 1-6 C-atoms, and their physiologically acceptable salts
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