DD297958A5 - DIBROMPROPANOL DERIVATIVES, METHOD OF PREPARING THEM AND THEIR USE - Google Patents

Abstract

The invention relates to novel dibromopropanol derivatives of the formula I in which R is an optionally substituted alkyl, cycloalkyl, aryl or heteroaryl radical, a process for their preparation and their use as microbicides for the protection of materials. Formula I

Description

Br R-CH-C-CHo-Br Ο »

II ²

OH CN

in the

R is an optionally substituted alkyl, cycloalkyl, aryl or heteroaryl radical, characterized in that acrylic compounds of the formula

HO-CH-C = CHo

II ² (N),

R CN

in the

R has the meaning given under formula (I),

optionally in the presence of an organic solvent which is inert under the reaction conditions, in a manner known per se.

5. Use of the dibromopropanol derivatives according to claims 1, 2 or 3 as Mikrobizideim material protection.

6. Use of the dibromopropanol derivatives according to claims 1, 2 or 3 as fungicides in crop protection.

The invention relates to novel 2-cyano-2,3-dibromo-propanol derivatives, a process for their preparation and their use as microbicides for the protection of materials.

It is already known to use brominated propanol derivatives, namely 2-bromo-2-nitro-3-hydroxy-propanol, as a preservative for functional liquids (see soap-oils-fats waxes 114 (1988) p.319-323). However, the effect of this microbicide on molds is unsatisfactory; It is therefore recommended to use this compound only in combination with very fungicidally active compounds such as isothiazolinones for the preservation of functional fluids (see Soap-Oils-Fats-Waxes loc cit, pp. 321-322). Another disadvantage of 2-bromo-2-nitro-3-hydroxypropanol, when used as a preservative, is that at pH> 7.5 with elimination of formaldehyde and nitrite, i. ecologically questionable compounds, hydrolyzed.

Surprisingly, it has now been found that certain novel dibromopropanol derivatives have a significantly improved microbicidal activity and also do not form toxic compounds in their hydrolysis. In addition, it has been found that some of these new dibromopropanol derivatives have not yet achieved with known fungicides effect against Fusaria, z. B. Fusarium nivale, and have some good action against mildew. The invention therefore relates to dibromopropanol derivative <3 of the formula

Br R-CH-C-CH ₂ -Br (I),

OH CN

in the

R is an optionally substituted alkyl, cycloalkyl, aryl or heteroaryl radical.

For example:

as optionally substituted alkyl radicals: C 1 -C ₂ -alkyl radicals such as methyl, ethyl, n-propyl, i-propyl, n-butyl, tert-butyl, n-hexyl, i-octyl and the n-dodecyl residue; by halogen atoms such as fluorine, chlorine or bromine, Ci-C ^ Alkylkylmercapto as

Methylmercapto, trifluoromethylmercapto and Dichlorfluormethylmercapto radicals, substituted C | -C ₄ -alkyl radicals such as

2-methoxyethyl, 2-ethoxyethyl, 2-chloroethyl, 2-trifluoromethylmercaptoethyl and 2,3-dibromopropyl rust; as unsubstituted or substituted cycloalkyl radicals, the cyclohexyl radical and by halogen, in particular chlorine atoms and / or

C 1 -C ₄ -alkyl substituted cyclohexyl radicals such as 4-methylcyclohexyl, 2,6-dimethylcyclohexyl and

4-tert-Butylcyclohexylrest;

as optionally substituted aryl radicals, in particular the phenyl radical and substituted by halogen, nitro or cyano

Phenyl radicals such as 2-chlorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-nitrophenyl and 2,6-dichlorophenyl radical;

as optionally substituted heteroaryl radicals the 2, 3 or 4-pyridyl radical and pyridyl radicals substituted by halogen and / or C, -C, -alkyl groups, such as the 6-chloropyridyl-2 radical.

R is preferably a C ₁ -C ₆ -alkyl or a phenyl radical which is substituted by chlorine or bromine, particularly preferably

a Cr-C _e alkyl.

As representatives of the dibromopropanol derivatives of the formula (I) according to the invention, the following compounds may be mentioned:

1,2-dibromo-2-cyano-3-hydroxy-butane, 1,2-dibromo-2-cyano-3-hydroxy-pentane, 1,2-dibromo-2-cyano-3-hydroxy-hexane, 1, 2-dibromo-2-cyano-3-hydroxy-4-methylpentane, 1,2-dibromo-2-cyano-3-hydroxy-4,4-dimethyl-pentane, 1,2-dibromo-2-cyano 3-hydroxy-nonane, i-dibromo-cyano-S-hydroxy-S-phenyl-propane, 1,2-dibromo-2-cyano-3-hydroxy-3- (4-bromophenyl) -propane,

i-dibromo-a-cyano-S-hydroxy-S 1 -chloro-phenyl-propane, 1,2-dibromo-2-cyano-3-hydroxy-3- (4-chloro-phenyl) -propane, 1,2-dibromo 2-cyano-3-hydroxy-3- (4-nitrophenyl) -propane, 1,2-dibromo-2-cyano-3-hydroxy-3- (2,6-dichlorophenyl) -propane, 1-dibromo ^ - cyano-S-hydroxy-S-cyclohexyl propane.

The dibromopropanol derivatives of the formula (I) according to the invention are obtained by bromination of acrylic compounds of the formula

HO-CH-C = CHo

I I <'»'

R CN

in the

R has the meaning given under formula (I),

receive.

The acrylic compounds of formula (II) are known and e.g. described in DE-OS 2155113. The invention also relates to this process for the preparation of Dibrompropanoi derivatives of the formula (I); the procedure is

characterized in that the acrylic derivatives dor formula (il), optionally in the presence of one of the

Reaction conditions inert organic solvent, brominated. Examples of organic solvents which are inert under the reaction conditions are aliphatic ones Chlorohydrocarbons such as methylene chloride, ethylene chloride, chloroform and carbon tetrachloride, aromatic Chlorinated hydrocarbons such as chlorobenzene and ortho-dichlorobenzene or glacial acetic acid called. The bromination is carried out at temperatures from O uis 80 ⁰ C, preferably at temperatures of 20 to 60 ⁰ C. For the bromination, an amount of bromine is used which amounts to 1 mole of the acryl compound of the formula (II) to be halogenated.

1 to 1.2 moles of bromine are omitted.

The addition of the bromine and the workup of the bromination mixture is carried out in known from preparative chemistry

Wise.

The dibromopropanols of the formula (I) according to the invention are distinguished by a strong microbicidal action and a good

fungicidal activity, especially against fusarium and mildew. They are substantially superior to the known brominated propanol derivative both in their fungicidal activity and in the breadth of their spectrum of activity. The

The invention therefore also relates to the use of the dibromopropanol derivatives of the formula (I) according to the invention as microbicides

for the protection of technical materials and as fungicides in plant protection.

Technical materials are inventively non-living materials prepared for use in the art

have been. For example, technical materials, the active ingredients according to the invention before microbial

Change or destruction should be protected, adhesives, glues, paper and cardboard, textiles, leather, wood, Paints and plastic articles, cooling lubricants and other materials that are attacked by microorganisms or

can be decomposed. In the context of the materials to be protected are also parts of production equipment, for example

Kühlwasserk 'skating, called, which can be affected by the proliferation of microorganisms. As part of the

adhesives, glues, papers and cartons, leather, wood,

Paints, coolants and heat transfer fluids. As microorganisms that can cause degradation or a change in the technical materials are

For example, bacteria, felts, yeasts, algae and slime organisms called. Preferably, the invention

Active substances against fungi, in particular molds, wood-discolouring and wood-destroying fungi (Basidiomycetes),

phytopathogenic fungi as well as against slime organisms and algae.

There may be mentioned, for example, microorganisms of the following genera: Alternaria, such as Alternaria tenuis, Aspergillus, such as Aspergillus niger, Botrytis, like Botrytis cinera, Chaetomium, such as Chaetomium globosum, Coniophora, like Coniophora puteana, Lentinus, like Lentinus tigrinus, Penicillin, such as Penicillium glaucum, Piricularia, like Piricularia oryzae.

Polyporus such as Polyporus versicolor, Aureobasidium such as Aureobasidium pullulans, Sclerophoma such as Sclerophoma pityophila, Trichoderrna such as Trichoderma viride, Escherichia such as Escherichia coli, Pseudomonas such as Pseudomonas aeruginosa, Staphylococcus such as Staphylococcus aureus.

Fungicides are used in crop protection for controlling Plasmadiophoromycetes, Oomycetes, Chytridiomycetes, Zygomycetes, Ascomycetes, Basidiomycetes, Deuteromycetes.

As pathogens of fungal diseases, which fall under the above-enumerated generic terms, may be mentioned, for example: Pythium species such as Pythium ultimum; Phytophthora species, such as Phytophthora infestans;

Pseudoperonospora species, such as Pseudoperonosphora humuli or Pseudoperonospora cubensis; Plasmopara species, such as Plasmopara viticola; Peronosphora species, such as Peronospora pisi or P. brassicae; Erysiphe species, such as Erysiphe graminis; Sphaerotheca species, such as Sphaerotheca fuliginea; Podosphaera species, such as Podosphaera leucotricha; Venturia species, such as Venturia inaequalis; Pyrenophora species, such as, for example, Pyrenophora teres or P. graminea (conidia form: Drechslera, Syn: helminthosphorium); Cochliobolus species, such as Cochliobolus sativus (conidia form: Drehslera, Syn: Helminthosporium); Uromyces species, such as Uromyces appendiculatus; Puccinia species, such as Puccinia recondita; Tilletia species, such as Tilletia caries; Ustilago species such as Ustilago nuda or Ustilago ivenao; Pellicularia species, such as, for example, Pellicularia sasakii; Pyricularia species, such as Pyricularia oryzae; Botrytis species, such as Botrytis cinerea; Septoria species such as Septoria nodorum; Leptosphaeria species, such as Leptosphaeria nodorum; Cercospora species, such as Cercospora canescens; Alternaria species, such as Alternaria brassicae;

Pseudocercosporella species, such as Pseudocercosporella herpotrichoides.

Some of the active compounds according to the invention have proven particularly suitable for controlling Fusarium species, such as, for example, Fusarium nivale, in particular on cereals. Furthermore, some of the active compounds according to the invention show good fungicidal action against powdery mildew, eg. On vines (Uncinula), apples and cereals such as barley and wheat. The good Pflellenverträglichkeit of the active ingredients in the control of plant diseases necessary concentrations allows treatment of aboveground plant parts, of plant and seed, and the soil.

Depending on the field of application, the active compounds according to the invention can be converted into the customary formulations, such as solutions, emulsions, suspensions, powders, pastes and granules.

These can be prepared in a conventional manner, for. Example, by mixing the active ingredients with an extender consisting of liquid solvent and / or solid carriers, optionally with the use of surfactants such as emulsifiers and / or dispersants, optionally in the case of using water as an extender organic solvents such as alcohols Aids can be used.

Liquid solvents for the active ingredients may be, for example, water, alcohols such as lower aliphatic alcohols, preferably ethanol or isopropanol, or benzyl alcohol, ketones such as acetone or methyl ethyl ketone, liquid hydrocarbons such as benzene fractions, halogenated hydrocarbons such as 1,2-dichloroethane. Microbicidal agents generally contain the active ingredients in an amount of from 1 to 95%, preferably from 10 to 75%. The use concentrations of the active compounds according to the invention depend on the nature and occurrence of the microorganisms to be controlled and on the composition of the material to be protected. The optimum amount used can be determined by test series. In general, the use concentrations are in the range of 0.001 to 5 wt .-%, preferably from 0.05 to 1.0Gew .-%, based on the material to be protected. The active compounds according to the invention can also be used in admixture with other known active ingredients. For example, the following active ingredients may be mentioned: benzyl alcohol mono (poly) hemiformal and other formaldehyde-releasing compounds, isothiazolinone derivatives, benzisothiazolinone, ρ hydroxybenzoic acid ester, benzimidazolyl-methylcarbamate, tetramethylthiuram disulfide, zinc salts of dialkyldithiocarbamates, 2,4, B ^ tetrachloroisophthalonitrile, hiazolylbenzimidazole, mercaptobenzothiazole, Organotin compounds, methylbisthiocyanate, 2-thiocyanatomethylthiobenzothiazole, phenol derivatives such as 2-phenylphenol, (2,2'-dihydroxy-5,5'-dichloro) diphenylmethane and 3-methyl-4-chlorophenol, N-trihalomethylthio compounds, such as folpet, fluorfolpet and dichlorofluamide, azole fungicides such as triadimefon, triadimenol and bitertanol.

example 1 The solution of 63.8 g (0.5 mol) of 2- (1-hydroxybutyU-acrylonitrile in 200 ml of chloroform is bsi 6O ⁰ C within 1.5 hours under Stirring was added dropwise with 79.9 g (0.5 mol) of bromine. After complete addition, the reaction solution for 3 hours at 60 ⁰ C.

touched. The solution is then cooled to room temperature and then washed 3 times with 10 ml sodium 10% sodium bisulphite solution. After drying the solution over sodium sulfate, the solution is concentrated on a rotary evaporator.

There are 133.7g (93.8% of theory) of an oil obtained, according to gas chromatographic analysis to 84.1%

1,2-dibromo-2-cyano-3-hydroxyhexane. The compound is characterized by its mass spectrum: M ⁺ 285.

Example 2

The solution of 31,7g (0,2MoI) 2- (a-hydroxybenzyl) acrylonitrile in 15OmI of chloroform is added dropwise at 6O ⁰ C within 1 hour under stirring with a solution of 32g (0,2MoI) of bromine in 50 ml of chloroform , After complete addition, the reaction mixture is stirred at 60 ⁰ C 3VI hours. It is then cooled to room temperature, stirred with 20 ml of sodium bisulfite solution, the aqueous phase separated and the organic phase dried over sodium sulfate. The crude product obtained after removal of the solvent is purified by column chromatography (eluent: toluene / ethyl acetate 9: 1, silica gel).

There are 31.7 g (= 49.7% of theory) i ^ -Dibrom ^ cyano-S-hydroxy-S-phenyl-propane obtained in the form of a yellow oil.

The compound is characterized by its IR spectrum (3470 cm -1 -OH; 2255 cm ^-1 -CN).

The physical properties of the dibromopropanols of the formula (I) which have been obtained in an analogous manner and in which R has the meaning also given in the table are summarized in the table below.

Table 1 Example

CH ₃ -C ₂ H ₆ -

CH '

CH

CH-

'3 nC ₆ H, 3

tC ₄ H ₉

Physical characteristics

¹ H NMRiO = I ₁ OIpPm -CH ₃ δ = 2.27 ppm -OH: δ = 1.15 ppm -CH ₃ δ = 2.26 ppm -OH δ = 3.7-41 ppm HC-OH, CH ₂ Br

¹ H-NMR: δ = 1.15 ppm -CH ₃

IR: 3470cm " ¹ -OH 2240cm" ¹ -CN

IR: 3480cm " ¹ -OH 2240cm" ¹ -CN

Mp: 119 ^° C

Cl

Fp.:123-128°C

IR: 3470cm " ¹ -OH 2250cm" ¹ -CN 1600cm " ¹ arom. = CH

Mp: 124-126 ⁰ C

Cl

Cl

Mass spectrum: m / e = 228 (M ⁺ -Br ₂ )

IR: 3470cm " ¹ -OH 2230cm" ¹ -CN

-5- 297 950

Anwendunysbelsplele

Example 14

To demonstrate the activity against fungi, the minimum inhibitory concentrations (MIC) of dibromopropanols according to the invention were determined:

An agar prepared from wort and peptone is admixed with active compounds according to the invention in concentrations of from 0.1 mg / l to 5,000 mg / l. After solidification of the agar contamination occurs with pure cultures of the test organisms listed in the table. After storage for 2 weeks at 28 ° C. and 60 to 70% relative humidity, the MIC is determined MIC is the lowest concentration of active substance in which no growth occurs due to the type of microbe used and is given in Table 2 below.

Table 2 MICs [mg / l] in the action of various bromopropanols on fungi

test organisms

Compounds of the invention according to Example 12 3 4 5 6 7

12 13 Comparison *

Alternaria tenuis 35 <1 50 20 20 150 20 75 35 75 200 Aspergillus niger 200 <20 200 200 200 100 200 150 200 100 > 1000 Aureobasidium pullulans 75 20 100 50 IiO 75 150 10 50 50 750 Chaetomium globosum 200 200 200 200 200 100 200 200 150 50 750 Cladosporium cladosporioides 20 <1 50 15 20 20 20 20 20 7.5 1000 Lentinustigrinus 50 2 100 50 50 20 35 200 20 20 750 Penicillium glaucum 50 <20 200 100 50 20 50 100 50 <20 1000 Sclerophoma pityophila 20 7.5 20 20 20 35 10 2 20 20 500 Trichoderma viride 200 200 350 200 200 200 500 200 200 500 > 1000

* 2-bromo-2-nitro-3-hydroxy-propanol

Example 15

Action against bacteria '

An agar containing Bouilon as nutrient medium is mixed with active compounds according to the invention in concentrations of 1 to 5,000 ppm. Then you infected the nutrient medium with each of the test organisms listed in Table II and keeps the infected medium for 2 weeks at 28 ⁰ C and 60 to 70% rel. Humidity. The MIC is the lowest concentration of active substance in which no growth occurs due to the microbe species used. The MIC values are shown in Table 3.

Table 3

Indication of the MIC values in mg / l for the action of the active ingredients listed below on bacteria.

MIC in mg / l of the active ingredients

test organisms Compound of Example No. 1 2 3 1000 1000 200 200 4 5 6 Escherichia coli Staphylococcus aureus 200 200 150 500 750 500 500 100

Example 16 (action against mucus organisms)

The compounds to be tested are, dissolved in a little acetone, in concentrations of 0.1 to 100 mg / l in aliens nutrient solution (Arch. Mikrobiol. 17,34 to 53 (1952)), in 41 sterile water, 0.2 g Ammonium chloride, 4.0g sodium nitrate, 1.0g dipotassium hydrogen phosphate, 0.2g calcium chloride, 2.05g magnesium sulphate, 0.02g ferric chloride and 1% caprolactam, at the beginning of the test, the individual nutrient solutions are mixed with mucilaginous organisms (approx ⁶ microbes / ml) isolated from spin-water circulations used in polyamide production, Nutrient solutions containing the iodopropargyl ether to be tested in at least minimum inhibitory concentration (MIC) are still perfectly clear after 3 weeks of culture at room temperature; the mucus formation occurring in active ingredient-free nutrient solutions after 3 to 4 days, caused by the strong multiplication of the microbes, and the turbidity associated therewith are prevented in them.

Table 4

MIC value [mg / l] of the dibromopropanols according to the invention in the case of action on slime organisms.

Dibromopropanol according to Example

MIC [mg / l]

5 - <10 5 - <10 5> 5 -

Example 17 (action against algae) A mixed culture of green, blue, brown and diatoms (Stichococcus bacillaris Naegeti, Euglena gracilis Klebs, Chlorella pyrenoidosa Chick, Phormidium foveoiarum Gomont, Oscillatoria geminata Meneghini and Phaeodactylum tricornutum Bohlin) is passed through air in aliens nutrient solution (Arch. Microbiol. 17, 34-53 [1952]) based on 4 L sterile water 0.2 g ammonium chloride, 4.0 g sodium nitrate, 1.0 g dipotassium hydrogen phosphate, 0.2 g calcium chloride, 2.05 g magnesium sulfate and 0, 02g contains iron chloride, given. After 2 weeks, the nutrient solution is stained deep green-blue by intensive algae growth. The dying off of the algae after addition of active compounds according to the invention is recognized by the decolorization of the nutrient solution.

Table 5

Algicidal concentrations [mg / l] of the dibromopropanols of the invention

Compound of Example No.

abtötonclo concentration [mg / l]

50 - <100> 50 - <100 50 50 - <100

Comparison: 2-bromo-2-nitro-3-hydroxy-propanol> 100

Example 18

Fusarium nivale test (rye) / seed treatment The active ingredients are applied as a dry dressing. These are prepared by mixing (stripping) the respective active ingredient with rock flour to a fine powdery mixture which ensures uniform distribution on the seed surface.

For pickling, shake the infected seed for 3 minutes with the mordant in a sealed glass bottle.

The rye is sown with 2 x 100 grain 1 cm deep in a standard soil and cultivated in the greenhouse at a temperature of about 10 ° C and a relative humidity of about 95% in seed boxes, which are exposed daily 15 hours of light.

Approximately 3 weeks after sowing, the plants are evaluated for symptoms of snow mold.

A clear superiority in effectiveness over the prior art show in this test z. B. the compounds according to the following preparation examples:

table

Fusarium nivale test (rye / seed treatment

active substance

Drug cost amount in mg / kg seed

efficiency

the untreated control

br

H ₁₃ C ₆ -CH-C-CH ₂ Br OH CN

(Example 6) Br

H ₅ C ₂ -CH-C-CH ₂ Br OH CN

(Example 4) according to the prior art: (US-PS4446076)

HnC-C-CHpBr 3, 2

500

500

500

89

91

66

Example 19

Erysiphe test (barley) / protective

Solvent: 100 parts by weight of dimethylformamide

Emulsifier: 0.25 parts by weight of alkylaryl polyglycol ether

To prepare a suitable preparation of active compound, 1 part by weight of active compound is mixed with the indicated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.

To test for protective activity, young plants are sprayed with the preparation of active compound in a dewy manner. After the spray coating has dried, the plants are spotted with spores of Erysiphe graminis f.sp. hordei pollinated.

The plants are placed in a greenhouse at a temperature of about 2O ⁰ C and a relative humidity of about 80% to promote the development of mildew pustules.

7 days after the inoculation the evaluation takes place.

A clear superiority in the effectiveness over the prior art show in this test z. B. the compounds according to the following preparation examples:

table Br I Active substance concentration in spray mixture in% by weight Efficiency in% of untreated control Erysipha test (barley) / protective Br- / V-CH-C-CH ₂ Br Wirksto.f I I OH CN 0.00025 75 (Example 8)

according to the prior art: (US Pat. No. 4,446,076)

Cl Br

-CH ₂ Br 0.00025 CN

Example 20

Erytiphe test (wheat oil / protective solvent: 100 parts by weight of dimethylformamide emulsifier: 0.25 part by weight of alkylarylpyclyglycol ether To prepare a suitable preparation of active compound, 1 part by weight of active compound is mixed with the stated amounts of solvent and emulsifier, and the concentrate is diluted with water to the desired concentration.

To test for protective activity, young plants are sprayed with the preparation of active compound in a dewy manner. After the spray coating has dried, the plants are spotted with spores of Erysiphe graminis f. sp. tritici pollinated.

The plants are placed in a greenhouse at a temperature of about 20 ⁰ C and a relative humidity of about BO% to promote the development of mildew pustules.

7 days after the inoculation the evaluation takes place.

A clear superiority in the effectiveness compared to the prior art show in a test z. B. the compounds according to the following preparation examples:

table

Erysiphe test (wheat) / protective

active substance

Agent concentration in spray mixture in% by weight

efficiency

the untreated control

Br Br- <V-CH-C-CHpBr

  - II

OH CN (Example 8)

0.0025

75

according to the prior art: (US Pat. No. 4,446,076)

Cl Br

-CH ₂ Br

0.0025

16

CN

Claims (4)

1. Dibromopropariol derivatives of the formula br R-CH-C-CHp-Br (D, II ² OH CN in the R is an optionally substituted alkyl, cycloalkyl, aryl or heteroaryl radical. 2. dibromopropanol derivatives according to claim 1, characterized in that R is a C ₁ -C ₆ -alkyl radical. 3. dibromopropanol derivatives according to claim 1, characterized in that R is a Cy-Cg-alkyl radical. 4. Process for the preparation of dibromopropanol derivatives of the formula