WO1986006254A1

WO1986006254A1 - Utilization of nitriles as antimicrobial agents

Info

Publication number: WO1986006254A1
Application number: PCT/EP1986/000221
Authority: WO
Inventors: Horst-Jürgen KRAUSE; Hans-Theo Leinen; Rudolf Lehmann
Original assignee: Henkel Kommanditgesellschaft Auf Aktien
Priority date: 1985-04-24
Filing date: 1986-04-16
Publication date: 1986-11-06
Also published as: DE3514689A1; EP0220250A1; JPS62502619A

Abstract

2,2-dibromine-3-oxonitriles have the formula (I), R-CO-CBr2-CN, wherein R is an aliphatic, cycloaliphatic, aromatic or heterocyclic, optionally substituted residue. Said nitriles are used as antimicrobial agents.

Description

"Use of nitriles as aritimicrobial agents"

The invention relates to the use of 2,2-dibromo-3-oxonitriles of the formula I,

R - CO- CBr2 - CN (I)

in which R represents an optionally substituted aliphatic, cycloaliphatic, aromatic or heterocyclic radical.

In the formula I given above, R can in particular be a straight-chain or branched alkyl radical having 3 to 19 carbon atoms, a cycloaliphatic radical optionally substituted by alkyl radicals and / or halogen atoms having 3 to 6 ring hydrocarbon atoms, an optionally substituted by alkyl radicals, alkoxy radicals, halogen atoms and / or nitro groups Phenyl or naphthyl radical or a heterocyclic radical containing five or six-membered oxygen, sulfur or nitrogen atoms.

The 2,2-dibromo-3-oxonitriles contemplated here for use as antimicrobial agents Almost all of them are new substances. Only the compounds of the formula I, in which R is a phenyl radical substituted by 1 to 3 chlorine atoms, can be regarded as known on the basis of the paper from Chemical Abstracts 84: 164406 x (1976); however, the use of these substances as antimicrobial agents is not mentioned in this reference. The compounds to be regarded as new and their preparation are not claimed here, rather they are the subject of the applicant's German patent application P (D 7322) filed at the same time.

The 2,2-dibromo-3-oxonitriles of the formula I are expediently prepared by adding a carboxylic acid ester of the formula II

R - CO - OR '(II)

in which R has the meaning given for formula I and in which R 'represents a straight-chain or branched alkyl radical having 1 to 4 carbon atoms, in the presence of a strong base, is reacted with acetonitrile, the 3-oxonitrile formed is isolated from the reaction mixture and in one against Bromine-inert solvent and in the presence of a hydrogen bromide acceptor, optionally with cooling, reacted with bromine and the resulting 2,2-dibromo-3-oxonitrile of the formula I is isolated.

Suitable starting materials for the preparation of the 2,2-dibromo-3-oxonitriles of the formula I by the process given above are, for example, esters of the following Carboxylic acids: butyric acid, valeric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, pivalic acid, 2,2-dimethylbutyric acid, 2,2-dimethylvaleric acid, 2-ethylhexanecarboxylic acid, cyclopropyl acid, 2-ethylcyclopropanecarboxylic acid, cyclobutanecarboxylic acid, 2-methylcyclopropanecarboxylic acid, 3-propylcyclobutanecarboxylic acid, cyclopentanecarboxylic acid, 1-ethylcyclopentanecarboxylic acid, 2-methylcyclopentanecarboxylic acid, 3-propylcyclopentanecarboxylic acid, cyclohexanecarboxylic acid, 1-methylcyclohexylcarboxylic acid, 2,2-dichloroacetic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcarboxylic acid, 2-methylcycloacid, 1-methylcyclopropane carboxylic acid, benzoic acid, 2-methylbenzoic acid, 3-methylbenzoic acid, 4-methylbenzoic acid, 2,4-dimethylbenzoic acid, 2-fluorobenzoic acid, 3-fluorobenzoic acid, 4-fluorobenzoic acid, 2-chlorobenzoic acid, 3-chlorobenzoic acid, 4-chlorobenzoic acid, 2 4-Dic chlorobenzoic acid, 3,4-dichlorobenzoic acid, 3,5-dichlorobenzoic acid, 2-bromobenzoic acid, 3-bromobenzoic acid, 4-bromobenzoic acid, 2,4-dibromobenzoic acid, 2,5-dibromobenzoic acid, 2-methoxybenzoic acid, 2-ethoxybenzoic acid, 3-methoxybenzoic acid, 4-methoxybenzoic acid, 3,4-dimethoxybenzoic acid, 2-nitrobenzoic acid, 3-nitrobenzoic acid, 4-nitrobenzoic acid, 2,4-dinitrobenzoic acid, 2,5-dinitrobenzoic acid, 3,5-dinitrobenzoic acid, 2-trifluoromethylbenzoic acid, 4-trifluoromethylbenzene, 1-trifluoromethylbenzoic acid Naphthalene carboxylic acid, 2-naphthalene carboxylic acid, furan-2-carboxylic acid, furan-3-carboxylic acid, 5-bromo-2-methylfuran-3-carboxylic acid, tetrahydrofuran-2-carboxylic acid, thiophene-2-carboxylic acid, thiophene-3-carboxylic acid, 5- Methylthiophene-2-carboxylic acid, tetrahydothiophene-3-carboxylic acid, picolinic acid, nicotinic acid and isonicotinic acid. The alcohol component of the carboxylic acid esters of formula II can consist of methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, sec-butanol and tert-butanol, methyl esters being particularly preferred.

The first stage of the process described above is the condensation of carboxylic acid esters with carboxylic acid nitriles known from organic synthesis, in which the corresponding 3-oxonitriles can be obtained in the presence of strong bases. According to the relevant literature, strong bases are in particular finely divided sodium amide and sodium hydride (see Houben-Weyl: Methods of Organic Chemistry, Volume 8, pp. 574-575; DE-OS 32 09 472). In contrast to the information in Houben-Weyl, it could be shown in connection with this invention that the condensation of fatty acid esters with acetonitrile can also be carried out with sodium methylate as the base if one works with a larger excess of acetonitrile and the alcohol formed in the condensation reaction continuously distilled off from the reaction mixture together with acetonitrile.

When working with sodium amide or sodium hydride as the condensing agent, the amount of acetonitrile used in the reaction is generally between 1.0 and 2.0 mol per mol of the carboxylic acid ester used. If sodium methylate is used as the condensing agent, it is advantageous to use 10 to 20 moles of acetonitrile per mole of carboxylic acid ester. The base provided as the condensing agent is advantageously used in amounts of 1 to 2 moles per mole of the carboxylic acid ester present.

When using sodium amide or sodium hydride as the condensing agent, the reaction is expediently carried out in an inert solvent, ether and aliphatic or aromatic hydrocarbons, such as, for example, cyclohexane, benzene, toluene or xylene, being suitable. When working with sodium methylate, no solvent is generally added, apart from the methanol normally introduced with the sodium methylate.

It has proven to be expedient to carry out the condensation reaction in an inert gas atmosphere, for example in a nitrogen or argon atmosphere. The reaction temperature can be in the range between 50 °, preferably 60 ° C and the reflux temperature of the respective reaction mixture.

When the condensation reaction is carried out, the mixture of carboxylic acid ester, condensing agent and, if appropriate, solvent is initially introduced and heated to the intended reaction temperature. The acetonitrile is then slowly introduced into the heated mixture with vigorous stirring. If sodium methylate is used as the strong base, a mixture of carboxylic acid ester and acetonitrile is added, the mixture is warmed to boiling and the sodium methylate solution is then slowly added. The resulting alcohol and the methanol introduced with the sodium methylate is continuously withdrawn from the reaction mixture together with acetonitrile via a corresponding distillation device.

The reaction mixture is usually worked up by adding a sufficiently large amount of water so that the solids present in the reaction mixture dissolve completely to form a two-phase system. The aqueous phase is separated off, the organic phase is optionally washed out with further water, the separated aqueous phases are combined, cooled and adjusted to a pH between 1 and 5 with cooling with aqueous mineral acid. The 3-oxonitrile separates out as a solid or as an oil and can be isolated in a known manner. When working up the reaction mixture it is also possible to separate the precipitate by suction filtration, wash it with a suitable solvent and then add it to an aqueous mineral acid solution for neutralization with very vigorous stirring. The amount of acid is chosen so that at the end of the reaction the aqueous solution has a pH between 1 and 5. Hydrochloric acid is preferred as the mineral acid.

When working up the reaction mixture, the treatment with the aqueous mineral acid should expediently be carried out at a temperature which does not exceed 10 ° C., preferably 0 ° C. The bromination of the 3-oxonitriles obtained in the second stage of the process for the preparation of the compounds of the formula I is carried out using elemental bromine in a solvent which is indifferent to bromine in the presence of a hydrogen bromide acceptor.

Chlorinated hydrocarbons, in particular methylene chloride, or glacial acetic acid are suitable as solvents. The procedure with methylene chloride has proven particularly useful since in this case it is possible to work in a two-phase mixture of solvent / water and the hydrogen bromide acceptor is present in dissolved form in the aqueous phase.

Bromine is preferably used in equimolar amounts, at most in an excess of 5 to 10 mol%. Weak bases, such as sodium hydrogen carbonate, potassium hydrogen carbonate, calcium carbonate or sodium acetate, are particularly suitable as hydrogen bromide acceptors.

The bromination of the 3-oxonitriles is advantageously carried out with cooling, temperatures between -10 to + 25 ° C. being preferred.

When the bromination is carried out, the 3-oxonitrile to be reacted, dissolved in the particular solvent, and the hydrogen bromide acceptor, optionally dissolved in water, are initially introduced and, with vigorous stirring and cooling, if appropriate, the corresponding amount of bromine, expediently also dissolved in the chosen solvent, slowly added. After the addition of bromine has ended, the reaction mixture is expediently converted to

Completion of the reaction was further stirred for 3 to 4 hours at room temperature.

To work up the reaction mixture, the aqueous phase which may be present is first separated off; the organic phase is washed out with water. Small amounts of bromine still present afterwards can be removed with the aid of sodium bisulfite or hydroxylamine hydrochloride. The organic solution is then dried with the aid of a suitable drying agent, for example anhydrous sodium sulfate, and the solvent is removed. The remaining 2,2-dibromo-3-oxonitrile in most cases already has a degree of purity which allows the products to be put directly to practical use. If desired, the products can be purified by recrystallization or distillation in a thin film evaporator.

Because of their microbistatic and microbicidal action against bacteria and fungi, the substances according to the invention are suitable for solving the various disinfection and preservation tasks in the non-therapeutic area. For use as an active ingredient in antimicrobial agents, the substances according to the invention can be incorporated into liquid, pasty or solid preparations. Such agents can be used in a wide variety of fields arrive, for example as cleaning, disinfecting and preserving agents for textiles, floors, hospital facilities, medical instruments, schools, bathing establishments, public transport, commercial operations such as dairies, breweries and laundries.

In addition to the active ingredients described, the finished antimicrobial agents generally contain other commonly used constituents which are selected depending on the intended form of use and the intended use. Suitable solvents for liquid preparations are water and conventional organic solvents, in particular alcohols and glycol ethers, optionally in a mixture with water. If, in addition to the antimicrobial action, an additional cleaning action is desired, the agents can contain nonionic surfactants or amphoteric surfactants. Addition products of 4 to 40, preferably 4 to 20 moles of ethylene oxide with 1 mole of fatty alcohol, alkylcyclohexanol, alkylphenol, fatty acid, fatty amine, fatty acid amide or alkanesulfonamide are suitable as nonionic surfactants. Addition products of 5 to 16 moles of ethylene oxide with coconut or tallow fatty alcohols, with oleyl alcohol and with mono-, di- or trialkylphenols and with monoalkylcyclohexanols with 6 to 14 carbon atoms in the alkyl radicals are of particular interest. Suitable amphoteric surfactants are the derivatives of secondary or tertiary aliphatic amines, it being possible for the aliphatic radicals to be straight-chain or branched and one radical to have 8 to 18 carbon atoms and another to be a solubilizing anionic group, for example a carboxy, sulfo, sulfa- to, phosphato or phosphono group. Framework substances can also be present in the antimicrobial agents; inorganic or organic salts, in particular inorganic or organic complexing agents, are suitable as such. Also useful are, for example, ortho-, pyro- and tripolyphosphates of Alkalimetallle, diaminetetraacetic acid, the alkali metal salts of chelating aminocarboxylic acids such as nitrilotriacetic acid and Ethyle¬-, the alkali metal salts of complex-forming phosphonic 1-Hydoxyethan-1,1-diphosphonic acid such as aminotrimethylenephosphonic acid and ethylenediamine, as well as the alkali metal salts of Sulfodicarboxylic acids, lactic acid, citric acid and tartaric acid. The acidic water-soluble salts of higher molecular weight polycarboxylic acids, for example polymers of maleic acid, itaconic acid, fumaric acid and citric acid, are also suitable as builders. Copolymers of these acids with one another or with other polymerizable substances, such as, for example, ethylene, propylene, acrylic acid, vinyl acetate, isobutylene, acrylamide and styrene, can also be used. If the antimicrobial agents contain organic solvents, the addition of solubilizers such as benzene, toluene and xylene sulfonic acid may be indicated in the form of their alkali salts.

The content of substances according to the invention in the ready-to-use antimicrobial agents is between 0.01 and 5 percent by weight, based on the total agent. Concentrates or solid mixtures containing up to 50 percent by weight of active ingredient can be put together for the production of such ready-to-use agents. The substances according to the invention can also be used for the preservation of technical products which lead to bacterial and fungal attack or other microbial

Destruction, such as paste, glue, emulsion paints and cutting and drilling oils. For this purpose, an addition of 0.01 to 2 percent by weight, based on the material to be preserved, is generally sufficient.

B e i s p i e l e

A. Preparation of the 2,2-dibromo-3-oxonitriles

example 1

130.2 g (1 mol) of methyl caproate and 548 g (13.4 mol) of acetonitrile were heated to boiling in a stirrer with stirrer, dropping funnel, gas inlet tube and attached distillation column while stirring and introducing nitrogen. In the boiling

The reaction solution was added dropwise over a period of 2 hours to 130 g of 30% by weight sodium methylate solution (54 g = 1 mol of sodium methylate). At the same time, methanol originating from the sodium methylate solution and formed during the reaction was distilled off together with acetonitrile via the distillation column. After the end of the addition of the sodium methylate solution, the distillation was continued until the boiling point of the pure acetonitrile was established in the top of the column and the elimination of methanol was complete. A total of 640 g of distillate was obtained during the distillation, which according to gas chromatographic analysis consisted of 24.1 percent by weight of methanol and 75.9 percent by weight of acetonitrile.

The sodium enolate salt of 3-oxooctanenitrile which precipitated out on cooling of the reaction mixture was separated off by filtration and washed with acetone. 134 g (83% of theory) of white salt were obtained. For conversion into the free 3-oxooctanenitrile, 27.6 g (0.17 mol) of the sodium enolate salt were stirred into a mixture of 100 ml of ice water and 58 ml of 10% by weight hydrochloric acid and acidified to pH 4. The deposited 3-oxooctanenitrile was taken up in methyl tert-butyl ether, the separated organic phase was washed neutral with water and dried over sodium sulfate. After distilling off the

Methyl tert-butyl ether remains 22.5 g (93% of theory) of 3-oxooctanenitrile which, according to gas chromatographic analysis, had a degree of purity of 98% by weight.

In a stirring apparatus, while stirring, cooling with ice and introducing nitrogen, 13.9 g (0.1 mol) of 3-oxooctanenitrile, dissolved in 75 ml of methylene chloride, and 22 g (0.22 mol) of potassium hydrogen carbonate, dissolved in 75 ml of water, were added 10.2 to 15 ° C. over the course of 90 minutes, 35.2 g (0.22 mol) of bromine, dissolved in 40 ml of methylene chloride, were added dropwise. The resulting mixture became. Complete the reaction for 4 hours at room temperature. The methylene chloride phase was then separated off. Excess bromine was removed with a little sodium bisulfite. The solution was then washed neutral with water and dried over sodium sulfate. The crude product remaining after the methylene chloride had been distilled off was distilled at 95 ° C./0.01 mbar using a thin-film evaporator. 22.1 g (75% of theory) of 2,2-dibromo-3-oxooctanenitrile (substance A) were obtained as a yellowish oil with n _D ²⁰ = 1.5055, which, according to gas chromatographic analysis, had a degree of purity of 97. Owned 2 percent by weight. analysis

C ₈ H ₁₁ NOBr ₂ (MM 296.989)

calculated (%): 32.35 C; 3.73 H; 4.72 N; 53.81 Br. Found (%): 31.9 C; 3.2 H; 5.0 N; 53.5 Br.

¹ H-NMR spectrum (60 MHz; CDCl ₃ )

= 3.10 (t); 1.75 (m); 1.35 (m); 0.90 (t)

Substances B to E were prepared in an analogous manner.

Substance B: 2,2-dibromo-3-oxodecanenitrile

yellowish oil with n ² _D ⁰ = 1.4978; Bp 120 ° C / 0.01 mbar

analysis

C ₁₀ H ₁₅ NOBr ₂ (MM 325.042)

calculated (%): 36.95C; 4.65 H; 4.31 Br; 49.17 Br. Found (%): 37.5 C; 4.65 H; 4.45 Br; 49.3 Br.

¹ H-NMR spectrum (90MHz: CDCl ₃ )

= 3.01 (t); 1.72 (m); 1.30 (m); 0.87 (t)

¹³ C-NMR spectrum (50 MH. CDCl ₃ )

= 189.48 (s); 113.53 (s); 34.02 (t); 33.87 (s);

31.53 (t); 28.80 (t); 28.62 (t); 24.64 (t);

22.53 (t); 14.01 (q). Substance C: 2,2-dibromo-3-oxododecanenitrile

yellowish oil with n _D ²⁰ = 1.4956

analysis

C ₁₂ H ₁₉ ONBr ₂ (MM 353.096)

calculated (%): 40.82 C; 5.42 H; 3.97 N; 45.26 Br. Found (%): 41.2 C; 5.16 H; 3.97 N; 45.4 Br.

Substance D: 2, 2-Dibrσm-3-oxotetradecanenitrile

colorless crystals; Mp 34 ° C

analysis

C ₁₄ H ₂₃ ONBr ₂ (MM 381.15)

calculated (%): 44.12 C; 6.08 H; 3.67 N; 41.93 Br. Found (%): 44.2 C; 6.45 H; 3.72 N; 42.6 Br.

Substance E: 2,2-dibromo-3-oxoeicosanitrile

colorless crystals with mp 57 ° C

analysis

C ₂₀ H ₃₅ NOBr ₂ (MM 465.32) calculated (%): 51.62 C; 7.58 H; 3.01 N; 34.35 Br. Found (%): 51.8 C; 7.8 H; 3.0 N; 33.7 Br.

Example 2

In a stirrer with stirrer, dropping funnel, gas inlet tube and reflux condenser, 28.8 g (0.6 mol) of sodium hydride (as a 50% by weight suspension in white oil) were suspended in 200 ml of absolute toluene, while stirring and introducing nitrogen, and 49.9 g ( 0.3 mol) 2-methoxybenzoic acid methyl ester added. The mixture was heated to 85 ° C. 24.6 g (0.5 mol) of absolute acetonitrile was dropped into the heated mixture over the course of 2 hours. The reaction mixture was then stirred at 90 ° C. for a further 15 hours. The mixture was then cooled to 0 ° C, 300 ml of ice water was carefully added with vigorous stirring, and stirring was continued at 0 ° C for 1 hour. The aqueous phase was then separated off and extracted with 100 ml of toluene. After cooling to 0 ° C., the aqueous phase was acidified to pH 1 with dilute hydrochloric acid. The precipitated product was washed with ice water and dried. The crude product (44 g) was recrystallized from isopropanol; 37.9 g (72% of theory) of 2-methoxybenzoylacetonitrile with mp 85-88 ° C were obtained.

8.7 g (0.05 mol) of 2-methoxybenzoylactonitrile were dissolved in 70 ml of methylene chloride. After adding a solution of 20 g of potassium hydrogen carbonate in 100 ml of water, the mixture was cooled to -5 ° C before vigorous 17.6 g (0.11 mol) of bromine in 30 ml of methylene chloride were added dropwise within 2 hours. After the bromine addition was complete, the reaction mixture was stirred at -5 to 0 ° C. for 90 minutes. Excess bromine was then removed by adding hydroxylamine hydrochloride, the organic phase was separated off, washed twice with 100 ml of water each time and dried over magnesium sulfate. After evaporation of the solvent in vacuo, 15.5 g (93% of theory) of 2-methoxybenzoyldibromoacetonitrile (substance J) remained as a yellow oil with n ² _D ⁰ = 1.5948.

analysis

C ₁₀ H ₇ HO ₂ Br ₂ (MM 333.006)

calculated (%): 36.07 C; 2.12 H; 4.21 N; 47.99 Br. Found (%): 35.90 C; 1.97 H; 4.11 N; 47.80 Br.

¹ H NMR Spectrum (60 MHz; CDCl ₃ ) = 3.92 (s); 6.95 - 7.77 (m)

IR (film): 1730 cm ^-1

The substances F to I and K to R were prepared in an analogous manner.

Substance F: benzoyldibromoacetonitrile

yellowish oil with n ² _D ⁰ = 1.5982; Bp 120 ° C / 0.01 mbar (thin film evaporator) analysis

C ₉ H ₅ NOBr ₂ (MM 302.952)

calculated (%): 35.68 C; 1.66 H; 4.62 N; 52.75 Br. Found (%): 34.0 C; 1.5 H; 4.7 N; 53.8 Br.

¹ H NMR Spectrum (60 MHz; CDCl ₃ ) = 8.19 (d, d); 7.59 - 7.33 (m)

¹³ C-NMR spectrum (50 MHz; CDCl ₃ )

= 179.9 (s); 135.2 (d); 131.2 (d); 128.8 (d); 128.4 (s); 114.1 (s); 31.4 (s).

Substance G: 2-methylbenzoyldibromoacetonitrile

yellowish 01 with n ² _D ⁰ = 1.5949

analysis

C ₁₀ H ₇ NOBr ₂ (MM 317.006)

calculated. (%): 37.89 C; 2.23 H; 4.42 N; 50.42 Br. Found (%): 39.90 C; 1.65 H; 4.46 N; 50.60 br.

Substance H: 3-methylbenzoyldibromoacetonitrile

yellowish oil with n ² _D ⁰ = 1.5991 analysis

C ₁₀ H ₇ NOBr ₂ (MM 317.006)

calculated (%): 37.89 C; 2.23 H; 4.42 N; 50.42 Br. Found (%): 38.20 C; 1.99 H; 4.38 N; 51.5 Br.

Substance I: 4-methylbenzoyldibromoacetonitrile

colorless crystals; Mp 65-69 ° C

analysis

C ₁₀ H ₇ NOBr ₂ (MM 317.006)

calculated (%): 37.89 C; 2.23 H; 4.42 N; 50.42 Br. Found (%): 37.40 C; 2.11 H; 4.39 N; 50.40 Br.

Substance K: 3-methoxybenzoyldibromoacetonitrile

yellowish oil with n ² _D ⁰ = 1.6048

analysis

C ₁₀ H ₇ NOBr ₂ (MM 317.006)

calculated (%): 36.07 C; 2.12 H; 4.21 N; 47.99 Br. Found (%): 36.00 C; 2.07 H; 4.26 N; 48.8 Br. Substance L: 4-methoxybenzoylbromoacetonitrile

colorless crystals; Mp 57-62 ° C

analysis

C ₁₀ H ₇ NO ₂ Br ₂ (MM 333.006)

calculated (%): 36.07 C; 2.12 H; 4.21 N; 47.99 Br. Found (%): 35.80 C; 2.09 H; 4.26 N; 47.60 br.

Substance M: 2-chlorobenzoyldibromoacetonitrile

yellowish oil with n ² _D ⁰ = 1.5966

analysis

C ₉ H ₄ NOBr ₂ Cl (MM 337.428)

calculated (%): 32.04 C; 1.19 H; 4.15 N; 47.37 Br;

10.51 cl. found (%): 31.6 C; 1.03 H; 4.50 N; 46.00 Br;

10.0 Cl.

Substance N: 3-chlorobenzoγldibromoacetonitrile

yellowish oil with n ² _D ⁰ = 1.6092 analysis

C ₉ H ₄ NOBr ₂ Cl (MM 337.428)

calculated (%): 32.04 C; 1.19 H; 4.15 N; 47.37 Br;

10.51 cl. found (%): 31.7 C; 1.25 H; 4.18 N; 46.5 Br; 10.50 cl.

Substance O: 4-chlorobenzoyldibromoacetonitrile

colorless crystals; Mp 41-42 ° C

analysis

C ₉ H ₄ NOBr ₂ Cl (MM 337.428)

calculated (%): 32.04 C; 1.19 H; 4.15 N; 47.37 Br;

10.51 cl. found (%): 31.17 C; 1.19 H; 4.06 N; 47.20 Br;

10.1 Cl.

Substance P: 4-bromobenzoyldibromoacetonitrile

colorless crystals; Mp 38-44 ° C

analysis

C ₉ H ₄ NOBr ₃ (MM 381.887) calculated (%): 28.31 C; 1.06 H; 3.67 N; 62.78 Br. Found (%): 27.90 C; 0.96 H; 3.66 N; 61.90 Br.

Substance Q: 1-naphthoyl dibromoacetonitrile

colorless crystals; Mp 48-51 ° C analysis

C ₁₃ H ₇ NOBr ₂ (MM 353.036)

calculated (%): 44.23 C; 2.00 H; 3.97 N; 45.27 Br. Found (%): 43.20..C; 1.91 H; 3.80 N; 44.8 Br.

Substance R: 2-naphthoyldibromoacetonitrile

colorless crystals; Mp 61-67 ° C

analysis

C ₁₃ H ₇ NOBr ₂ (MM 353.036) m calculated (%): 44.23 C; 2.00 H; 3.97 N; 45.27 Br. Found (%): 43.50 C; 1.91 H; 3.75 N; 45.00 Br.

The 2,2-dibromo-3-oxonitriles shown in Examples 1 and 2 are summarized in Table I below together with their physical data.

B. Antimicrobial effectiveness

1. Microbistatic effectiveness

The microbistatic activity of substances A to R according to the invention was determined in relation to the following test germ suspensions:

1. Staphylococcus aureus 2 x 10 ⁹ germs / ml

2. Escherichia coli 2 x 10 ⁹ germs / ml

3. Pseudomonas aeruginosa 5 x 10 ⁸ germs / ml 4. Candida albicans 2 x 10 ⁸ germs / ml

5. Aspergillus niger 5 x 10 ⁷ germs / ml

6. Penicillium camerunense 5 x 10 ⁷ germs / ml

The inhibitory concentrations of the compounds to be examined were determined using the dilution test according to

Guidelines for testing chemical disinfectants of the German Society for Hygiene and Microbiology (1972) determined. The experiments were carried out in sterile test tubes containing 1 to 3 standard I broth (pH 7.5 Merck) for the germs and 4 to 6 wort broth (pH 5.5, Merck) for the germs. After the addition of the active ingredients, the volume of nutrient solution in the tubes was 5 ml in each case. Then 0.1 ml of the test microbial suspension of the stated concentration was introduced into the tubes. The nutrient solution samples inoculated with bacteria were stored in the incubator at 37 ° C. for 3 days. The samples inoculated with mushrooms were incubated at 30 ° C for 4 days. It was then determined which concentration of active ingredient added to the nutrient medium had just inhibited the growth of the germs. The value found in this way was called the inhibitory concentration. The following active ingredient concentrations in ppm were tested: 1,000, 500, 250, 100, 50 and 10.

The inhibitory concentrations shown in Table II below were determined for substances A to R.

2. Microbicidal effectiveness

The microbicidal activity of substances A to R according to the invention was determined in relation to the following test germ suspensions:

1. Staphylococcus aureus 2 x 10 ⁹ germs / ml 2. Escherichia coli 2 x 10 ⁹ germs / ml

3. Pseudomonas aeruginosa 5 x 10 ⁸ germs / ml

4. Candida albicans 2 x 10 ⁸ germs / ml

5. Aspergillus niger 5 x 10 ⁷ germs / ml

6. Penicillium camerunense 5 x 10 ⁷ germs / ml

The killing times of the products to be examined were determined using the suspension test. Using water with a hardness of 17 ° dH, test solutions were prepared which contained 2000 or 500 ppm of active ingredient. At room temperature, 0.1 ml of test germ suspension were pipetted into test tubes and mixed with 10 ml of the test solutions described above. After different exposure times of up to 60 minutes, approximately 0.05 ml of material was removed from the test tubes using an inoculation loop and spread on a nutrient agar which contained 3% Tween 80 and 0.3% lecithin as a stripper. The nutrient medium consisted of 2.5 weight percent standard I broth (Merck) for germs 1 to 3 and pH 5 (Merck) for germs 4 to 6, each containing 1.2 weight percent agar for solidification. The samples were incubated at 37 ° C and 30 ° C, respectively. After 2 to 3 days, the cultures were assessed macroscopically for growth and in this way the kill time or the residual germ content is determined. The results found are shown in Table III below.

In Table III, "+" means less than 50, "++ * 'less than 200 and" +++ "more than 200 residual germs after an exposure time of 60 minutes. The numerical values given in the individual columns represent the exposure time in minutes.

Claims

Patent claims

1. Use of 2,2-dibromo-3-oxonitriles of the formula I,

R - CO - CBr ₂ - CN (I)

in which R represents an optionally substituted aliphatic, cycloaliphatic, aromatic or heterocyclic radical, as antimicrobial agents.

2. Use of 2,2-dibromo-3-oxonitriles according to claim 1, characterized in that in the formula IR a straight-chain or branched alkyl radical having 3 to 21 carbon atoms, an optionally substituted with alkyl radicals cycloaliphatic radical having 3 to 6 ring hydrocarbon atoms, one phenyl or naphthyl radical optionally substituted with alkyl radicals, alkoxy radicals, halogen atoms or nitro groups or a heterocyclic radical containing five or six-membered oxygen, sulfur or nitrogen atoms.