NO812580L - MICROBICID AGENTS FOR THE PROTECTION OF TECHNICAL MATERIALS - Google Patents

Description

The invention relates to the use of 4-nitroso-pyrazoles in microbicide agents for the protection of technical materials.

It is known that certain i4.-nitroso-pyrazoles such as e.g. 3, 5-dimethyl-1-iso-propyl-4-nitroso-pyrazole t- 3,5-dimethyl-1-(4-chloro-phenyl)-4-nitroso-pyrazole and 3»5-dimethyl- 1 -

(4-methyl-phenyl)-4-nitroso-pyrazole has fungicidal and partly also bactericidal properties and can be used in plant treatment. shoot agent (British Patent 786,753, US Patent 2,410,734 and Phytopathology 39, 721-751 (1949)).

From US patent 2 831 866 it is known that nitroso-pyrazoles are essentially suitable for combating pathogenic fungi in humans and animals.

The invention relates to a microbicide agent for the protection of technical materials, as the agent is characterized by containing 4-nitroso-pyrazoles with the formula

R<1>cyanoalkyl with up to 6 carbon atoms, C, to Cg -cyclo-alkyl which is optionally interrupted by -S-, -SO- or -SO2-, phenyl which is substituted with nitro, C, to C -alkyloxy,

■ 4

and/or phenylsulfonyl, benzyl, which is optionally substituted with halogen, nitro, C- to C 4 -alkyl and/or C 1 to C 4-alkoxy, or a 5-ringed or 6-ringed heterocyclyl, containing 1 to 2 nitrogen atoms and is optionally, one sulfur atom, and which is optionally benzanellated.

Surprisingly, the microbicide agents applicable according to the invention for the protection of technical materials and the corresponding formula I show considerably higher fungicidal and bactericidal effects than known compounds of analogous constitution and the same direction of action.

The cyanoalkyl residue of the 4.-nitroso-pyrazoles that can be used according to the invention can be linear or

branched hydrocarbon residues which may be substituted with,

one or more (usually 1 to 3) cyano groups. Preferably, the cyanoalkyl residues contain a terminally placed cyano group. For example, the following cyanoalkyl residues should be mentioned: Cyanomethyl, 2-cyano-ethyl, 2-cyano-propyl and 1-cyano-1-methyl-ethyl.

The cycloalkyl residue of the 4-nitrosopyrazoles usable according to the invention are cyclic hydrocarbon residues with 3 to 8 carbon atoms. Cycloalkyl residues with 5 or 6 carbon atoms should preferably be mentioned. For example, the following cycloalkyl residues must be mentioned: , ,

Cyclopentyl and cyclohexyl.

The ring may also contain cycloalkyl residues

one or more, (usually 1 to 2) thio-, sulfo- and/or' sulfoxy groups. Preferably, the cycloalkyl radicals contain a thi'o-, sulfo- and/or sulfo-oxy group. For example, mention should be made of S, S-dioxo-tetrahydrothiophen-3-yl •

5- or 6-ring heterocycles of the 4-nitroso-pyrazole that can be used according to the invention usually contain 1' to 2 nitrogen atoms, optionally a sulfur atom, and may optionally be benzannelated. Preferably, mention should be made of 5- or 6-ring heterocycles containing 1 or 2 nitrogen atoms, or 1 nitrogen atom and 1 sulfur atom, the latter being benzanellated.

For example, the following 5- or 6-ring heterocycles should be mentioned:

Pyridine, piperidine and benzthiazole.

Alkyl and alkoxy residues contain a straight or branched hydrocarbon residue with usually 1 to 4 carbon atoms. For example, the following alkyl and alkoxy acid residues should be mentioned: Methyl, ethyl, propyl, isopropyl, butyl and isobutyl and methoxy, ethoxy, propoxy, isopropoxy, butoxy and isobutoxy. Preferred alkyl and alkoxy acid residues are methyl and ethyl residues and methoxy-o-g ethoxy acid residues. Preferred microbicidal agents according to the invention for the protection of technical materials contain 4-nitroso-pyrazoles of formula i

in which J

R 2 means cyanoethyl, phenyl, which is substituted with nitro, methyl, methoxy and/or phenylsulfonyl, benzyl, pyridinyl, Dvrimidvl. beny,t i a z ol we or the rest

In particular, microbicide agents are preferred for the protection of technical material containing 4-nitroso-pyrazoles with formula

in which

R 3 means cyanoethyl, phenyl, which is substituted with nitro, methoxy and/or phenylsulfonyl, pyrimidinyl, benzthiazolyl

or restei

Some of the microbicide agents according to the invention for the protection of technical materials are new. As new compounds, 4-nitroso-pyrazoles with the formula must be mentioned

in which

R 3 means cyanoethyl, phenyl, which is substituted by nitro, methoxy and/or phenylsulfonyl, pyrimidinyl, benzthiazolyl

4-nitroso-pyrazoles can be prepared as hydrazine derivatives with the formula !

what the heck

in

R has the above meaning

or their salts are reacted with isonitroso-acetylacetone in . aqueous dispersion at temperatures between -20 and + 50°C. The turnover can be shown by the following reaction equation:

The hydrazine derivatives are known in and of themselves (Methodicum Chimicum, volume 6, pages 75-131, Georg Thieme Verlag, Stuttgart 1974-) and can be prepared according to known methods, for example by reacting hydrazine with acrylonitrile, of diazo compounds with bisulfites, nitroso compounds with reducing agents, or of haloaronates with hydrazine. It is also possible, instead of hydrazine derivatives, to use the precursors such as, for example, hydrazine and acrylonitrile without intermediate isolation of hydrazine derivatives for the production of 4-nitroso-pyrazoles.

The salts of the hydrazine derivatives can be prepared by reacting hydrazine derivatives with an acid, for example

show a mineral acid such as hydrochloric or sulfuric acid.

Isonitroso-acetylacetone, which can be used as a further starting component, is likewise known in and of itself (Wolff, Liebig's Annalen der Chemie, 325»139), and can be produced from acetylacetone and a nitrite in the presence of an acid.

When preparing the 4-nitroso-pyrazoles, the reaction temperature can be varied within a large range. Usually one works in temperature ranges from 120 to

+ 50°C, preferably in the temperature range from 0 to 30°C. The procedure is usually carried out at normal pressure.

The starting compound is usually used in approximately equimolar amounts. Between 0.5 and 1.5, preferably between 0.8 and 1.2 moles of isonitrosoacetylacetone is used per mole of hydrazine derivatives.

The method according to the invention can, for example, be carried out as follows: The hydrazine derivative is dissolved in water and cooled with ice. " To this solution, an aqueous solution of isonitrosoacetylacetone is added dropwise. The reaction mixture is stirred for 1 to 3 hours. As far as the products thereby appear crystalline, they are isolated by suction. Otherwise, the work-up can take place according to usual methods, for example by extraction with a practically non-miscible organic solvent such as diethyl ether, - separation of the organic extracts and evaporation of these solutions. The product can optionally also be recrystallized.

Technical materials that must be protected using 4-nitroso-pyrazoles from a microbial change and destruction are, for example, adhesive substances, glue, paper and cardboard, textiles, leather, wood, coating agents, plaster, cooling lubricants and plastic articles , which are attacked and can be destroyed by microorganisms. Within the framework of the materials to be protected, parts of production facilities such as cooling water and cooling lubricant circuits, whose functionality can be affected with the help of microorganisms, must also be mentioned.

Microorganisms that can cause a breakdown

or a change in the technical materials are, for example, bacteria, fungi, yeast, algae, mucus and viruses. Preferably, the 4-nitroso-pyrazoles according to the invention also work against bacteria.

Microorganisms should be mentioned, for example

of the following genera:

Escherichia, such as Escherichia coli,

Pseudomonas, such as Pseudomonas aeruginosa, Staphylococcus, such as Staphylococcus aureus, Alternaria, such as Alternaria ténuis,

Aspergillus, such as Aspergillus niger,

Chaetomonium, as Chaetomohium .globosum, Coniophora, as Coniophora cerebella,

Lentinus, as Lentinus tigrinus,

Penicillium,, such as Penicillium glaucum,

Polyporus, such as Polyporus versicolor,

Pullularia, such as Pullularia pullulans,

Sclerophoma, such as Sclerophoma pityophila, Trichoderma, such as Trichoderma viride.

Depending on their area of application, the 4,-nitroso-pyrazoles according to the invention can be transferred in the usual formulations such as solutions, emulsions, suspensions, powders, pastes and granules. These can be produced in a manner known per se, e.g. by mixing the active substances with a thickening agent with liquid solubilizing agents and/or solid carriers, possibly using surface-active agents, such as emulsifiers and/or dispersing agents, as, for example, in the case of using water softening agents, organic solubilizing agents can optionally be used with the help of solubilizing agents.

Organic solvents for the active substances can for example be 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 gasoline fractions, chlorinated hydrocarbons such as 1, 2-dichloroethane. .

The application concentration of 4-ritroso-pyrazoles according to the invention depends on the type and near-

weather of the micro-organisms to be combated, as well as .according to the composition of the material to be protected. The optimal amount of application can be determined with the help of test series. Usually the application concentration is

in the range from 0.001 to 5% by weight, preferably from 0.05 to 0.5% by weight, referred to material to be protected.

The new active substances according to the invention

can also be present in a mixture with other known active substances. For example, the following active substances should be mentioned: Benzimidazolyl r methyl carbamate, tetramethyl thiuram disulfide, N-fluorodichloromethylthio-phthalimide and N,N-dimethyl-N'-phenyl-(N-fluorodichloromethylthio)-sulfamide, formaldehyde, de-splitting compounds which hemif ormals, • oxazolidines, hexa-hydro-s-triazines, n-methylolamides and phenol derivatives, such as p-chloro-m-cresol, 2-phenyl-phenol, (2,21-dihydroxy- 5, 5'-dichloro) -diphenylmethane.

A. Manufacturing examples

Example- 1

To a solution of 19.5 g (0.1 mol) of benzyl hydrazine dihydrochloride in 200 ml of water, 12.9 g (0.1 mol) of isonitroso-acetylacetone in 100 ml of water are added dropwise at 1 - 5°C with vigorous stirring. After stirring for 2 hours at room temperature, the reaction mixture is extracted. twice with each time 100 ml of ether, and then evaporate the combined ether extracts. 18 g (84% of the theoretical value) of 3,5-dimethyl-1-benzyl-4-nitrosopyrazole are obtained in the form of blue-green crystals.

After recrystallization from benzene/naphtha, the pure substance with a melting point of 64°C is obtained.

Example 2

To a solution of 60 g (1.2 mol) of hydrazine hydrate in 50 ml of water, 106 g (2 mol) of acrylonitrile are added dropwise at 0 - 5°C. Stir for 1/2 hour at 20°C, and then add 400 ml of water to the reaction mixture.

This solution is dripped at 0 - 5°C during approx. 2 hours under vigorous stirring 129 g (1 mol) iso-•ni.tr oso-acetylacetone in 800 ml of water. Stirring is continued for 1 hour at approx. 50°C and then suction off the precipitate which is washed with water and then dried in air.

130 g (73% of the theoretical) of 3,5-dimethyl-1-(2-cyanoethyl)-4-nitroso-pyrazole are obtained in the form of blue crystals of m.p. 68 -. 70°C.

In an analogous manner to that discussed in example 1, it was produced:

Example 10

To a well-stirred solution of 12.9 g (0.1 mol) of isonitrosoacetylacetone in 10.0 ml of water, an aqueous solution of benzylhydrazine, (prepared from 9»4 g (0, 1 mol) benzylhydrazin-dihydrochlor.id, 150 ml water, and 16.8 g (0.2 mol) ■ sodium hydrogencarbonate). After approx. 1/10 of benzylhydrazine — the solution has been added, some seed crystals of 3,5-dimethyl-1-benzyl-4-nitroso-pyrazole are added. It is then stirred for 5 hours at a temperature of 0 - 20°C. The blue crystalline precipitate is then separated, washed with cold water and dried in air.

20 g (93% of theoretical) of 3,5-dimethyl-1-benzyl-4-nitroso-pyrazole are obtained in the form of blue crystals of sni.p. 6 (°C.

B. Application examples

Example- 11

To demonstrate the effect against fungi, the minimum inhibitory concentration (MIC) of active substances according to the invention is determined:

An agar made from beer wort and peptone is mixed with active substances according to the invention in concentrations from 0.5 mg/litre to 5000 mg/litre. After the agar solidifies, contamination takes place with pure cultures of the test organisms listed in the tables. After 2 weeks of storage at 28°C and 60 to 70% relative humidity, the MHK is determined. MHK is the lowest concentration of active substance, where growth does not take place with the type of microbe used, it is indicated in the following table:

Example 12 (Effect against bacteria)

An agar, which as nutrient medium contained broth, is mixed with the active substances listed in Table II in concentrations from 1 to 5000 ppm. The nutrient medium is then infected each time with Escherichia coli or Staphylococcus aureus and the infected medium is kept for 2 weeks at 28°C and 60 to 70% relative humidity. MHK is the lowest concentration of active substance, where no growth of the microbe types used takes place.

The MHK values are reproduced in table II.

Example 13 (Effect as slime organisms).

The compound according to Table III is used each time in concentrations from 0.1 to 100 mg/l in Allen's nutrient solution (Arch. Mikrobiol. 17, 3U to 53 (1052 )), which in 4 liters of sterile water contains 0.2 g of ammonium chloride, l ± 0 g of sodium nitrate, 5.0 g of dipotassium hydrogen phosphate, 0.2 g of calcium chloride, 2.05 g of magnesium sulfate, 0.02 g of ferric chloride, and 1 weight of caprolactam. dissolved in a little acetone. Shortly beforehand, the nutrient solution is infected with slime organisms (approx. 10^ germs/ml), was isolated from the binding water circuit used in the polyamide production. ready after 3 weeks of culture at room temperature, i.e.

the effective substance-free nutrient solutions after 3 to 4 days noticeable strong multiplication of the microbes of the loop -

formation does not occur. From the MHK values listed in Table III, the antimicrobial effect of the active substances according to the invention on slime organisms is evident.

Example 14 (preservation of a cooling lubricant)

A cooling lubricant based on mineral oil is mixed with 0.2% 3'5-dimethyl-1-benzyl-4-nitroso-pyrazole, and then diluted with 5% water, so that the dilution for use contains 0.01% active substance according to the invention.

Over the course of 12 weeks, the use dilution is massively contaminated daily with microbes (bacteria and moulds), which originate from a microbially spoiled cooling lubricant. To check the final effect of the microbicide, the germ count is determined each time 23 hours after a contamination.

Results: Even after 12 weeks, the conserved cooling lubricant is still germ-free, however inside-. holds a non-preserved cooling lubricant that was treated in the same way, already after the first contamination approx. 10 n germs/ml, and after 12 weeks shows clear signs of microbial•degradation.

Claims (2)

1. Microbicide agent for the protection of technical materials, containing 4-nitroso-pyrazoles with formula R means cyanoalkyl with up to 6 carbon atoms, to Cg-cycloalkyl, which is optionally interrupted by -S-, -SO-, or . -SO2 -, phenyl, which is substituted by nitro, to C^- alkoxy, and/or phenylsulfonyl, benzyl, which is optionally substituted with halogen, nitro, C₁ to C₁ -alkyl and/or C 1 to C 4 -Alkoxy, or means a 5-ring or 6-ring heterocycle, containing 1 to 2 nitrogen atoms and optionally a sulfur atom, which is optionally benzanellated. 2. Microbicidal agent for the protection of technical materials according to claim 1, containing 4-nitroso-pyrazoles with the formula R 2 means cyanoethyl, phenyl, which is substituted by nitro, methoxy and/or phenylsulfonyl, benzyl, pyridinyl, pyrimidinyl, benzthiazolyl or the rest 3- Microbicide agent for the protection of technical materials according to claims 1 and 2, containing 4-nitroso-pyrazoles with the formula in which R 3 means cyanoethyl, phenyl, which is substituted by nitro, methoxy and/or phenylsulfonyl, pyrimidyl, benzthiazolyl or the rest iL.4 - nitroso-pyrazoles medi formula in which R 3 means cyanoethyl, phenyl, which is substituted by nitro, methoxy and/or phenylsulfonyl, pyrimidyl, benzthiazolyl or the rest