DE3514689A1 - USE OF NITRILE AS AN ANTIMICROBIAL ACTIVE SUBSTANCE - Google Patents

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 antimicrobial 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 is an optionally substituted one represents aliphatic, cycloaliphatic, aromatic or heterocyclic radical.

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

Those considered here for use as antimicrobial agents drawn 2,2-dibromo-3-oxonitrile almost all make new fabrics Only the compounds of the formula I in which R is one with 1 to 3 chlorine atoms Substituted phenyl radical means are based on the report from Chemical Abstracts 84: 164406 x (1976) to be considered known; a use of these substances as However, antimicrobial agents are not mentioned in this literature reference. the connections to be regarded as new and their production are not claimed here, rather, they are the subject of the German patent application filed at the same time P (D 7322) of the applicant.

The 2,2-dibromo-3-oxonitriles of the formula I are more expediently prepared Way so that a carboxylic acid ester of the formula II, R - CO - ORt (11) in the R has the meaning given for formula 1 and in RE a straight-chain one or represents branched alkyl radical having 1 to 4 carbon atoms, in the presence reacts a strong base with acetonitrile, the resulting 3-oxonitrile from the Reaction mixture isolated and in a bromine-indifferent solvent and in the presence of a hydrogen bromide acceptor, optionally with cooling, with bromine and the resulting 2,2-dibromo-3-oxonitrile of the formula I is isolated.

As a starting material for the production of 2,2-dibromo-3-oxonitrile of the formula I according to 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, cyclopropanecarboxylic acid, l-methylcyclopropanecarboxylic acid, 2-ethylcyclopropanecarboxylic acid, cyclobutanecarboxylic acid, 2-methylcyclopropanecarboxylic acid, 3-propylcyclobutanecarboxylic acid, cyclopentanecarboxylic acid, l-ethylcyclopentanecarboxylic acid, 2-methylcyclopentanecarboxylic acid, 3-propylcyclopentanecarboxylic acid, cyclohexanecarboxylic acid, l-methylcyclohexylcarboxylic acid, 2-methylcyclohexanecarboxylic acid, 3,4-dimethylcyclohexanecarboxylic acid, 2,2-dichloro-l-methylcyclopropanecarboxylic 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-dichlorobenzoic 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-nitrobenzoic acid, 2-trifluoromethylbenzoic acid, 4-trifluoromethylbenzoic acid, l-naphthoic acid, 2-naphthoic 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 ester of the formula II can be from Methanol, ethanol, n-propanol, i-propanol, n-butanol, i-butanol, sec-butanol and tert-butanol, with methyl esters being particularly preferred.

The first stage of the procedure described above is the condensation of carboxylic acid esters known from organic synthesis with carboxonitriles, in which the corresponding 3-oxonitriles in the presence of strong bases can be obtained. As strong bases come according to the information of the relevant Literature especially finely divided sodium amide and sodium hydride into consideration (see Houben-Weyl: Methods of Organic Chemistry, Volume 8, pp. 574-575r DE-OS 23 09 472). In contrast to the information in Houben-Weyl, in connection with this Invention can be shown that the condensation of fatty acid esters with acetonitrile Can also be carried out with sodium methylate as the base, if one is using a larger one Excess acetonitrile works and that formed in the condensation reaction Alcohol is continuously distilled off from the reaction mixture together with acetonitrile.

When using sodium amide or sodium hydride as the condensing agent works, the amount of acetonitrile used in the reaction is generally between 1.0 and 2.0 moles per mole of the carboxylic acid ester used. Becomes sodium methylate 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 expedient used in amounts of 1 to 2 moles per mole of the carboxylic acid ester present.

When using sodium amide or sodium hydride as a condensing agent the reaction is expediently carried out in an inert solvent, with Ethers and aliphatic or aromatic hydrocarbons such as cyclohexane, Benzene, toluene or xylene come into consideration. When working with sodium methylate is generally no solvent added if one of the sodium methylate normally introduced methanol refrains.

It has proven to be useful to carry out the condensation reaction in an inert gas atmosphere, for example in a nitrogen or argon atmosphere perform.

The reaction temperature can range between 500, preferably 600C and the reflux temperature of the respective reaction mixture.

When carrying out the condensation reaction, the mixture is placed from carboxylic acid ester, condensing agent and optionally solvent before and heats it to the intended reaction temperature. In the heated mixture is then slowly introduced the acetonitrile with vigorous stirring. If you use sodium methylate as a strong base, a mixture of carboxylic acid ester and acetonitrile is presented, heated to boiling and then slowly introduces the sodium methylate solution.

The alcohol formed during the reaction and the methanol introduced with the sodium methylate via an appropriate distillation device continuously withdrawn from the reaction mixture together with acetonitrile.

The reaction mixture is normally worked up Add a sufficient amount of water so that the present in the reaction mixture Completely dissolve solids to form a two-phase system. The watery one Phase is separated off, the organic phase is washed out with further water if necessary, the separated aqueous phases are combined, cooled and with cooling aqueous mineral acid adjusted to a pH between 1 and 5.

The 3-oxonitrile separates out as a solid or as an oil and can be isolated in a known manner.

However, this can also be used for working up the reaction mixture be that the precipitate present is separated off by suction filtration, with Washes with a suitable solvent and then taking it to neutralize enters into an aqueous mineral acid solution with vigorous stirring. Thereby the amount of acid chosen so that at the end of the reaction the aqueous solution has a pH between 1 and 5 has. Hydrochloric acid is preferred as the mineral acid.

Appropriately when working up the reaction mixture the treatment with the aqueous mineral acid can be carried out at a temperature, which does not exceed 100C, preferably OOC.

Those in the second stage of the above process of manufacture of the compounds of the formula I carried out bromination of the 3-oxonitriles obtained takes place with elemental bromine in a bromine-indifferent solvent in Presence of a hydrogen bromide acceptor.

Chlorinated hydrocarbons are particularly suitable as solvents Methylene chloride, or glacial acetic acid. The way of working with methylene chloride has turned out to be particularly good proven, since in this case a two-phase solvent / water mixture is used can be and the hydrogen bromide acceptor in dissolved form in the aqueous phase is present.

Bromine is preferred in equimolar amounts, if need be in an excess from 5 to 10 mol% are used. Particularly suitable as hydrogen bromide acceptors are weak bases such as sodium hydrogen carbonate, potassium hydrogen carbonate, calcium carbonate or sodium acetate.

The bromination of the 3-oxonitriles is expediently carried out with cooling carried out, temperatures between -10 to + 250C are preferred.

When carrying out the bromination, the 3-oxonitrile to be converted is dissolved in the respective solvent, and the hydrogen bromide acceptor, if appropriate dissolved in water, submitted and with vigorous stirring and optionally cooling the corresponding amount of bromine, expediently also in the chosen one Solvent dissolved, added slowly. After the end of the addition of bromine, the reaction mixture becomes expediently for a further 3 to 4 hours to complete the reaction Stirring at room temperature.

To work up the reaction mixture, the optional the aqueous phase present is separated off; the organic phase is washed out with water. Small amounts of bromine that are still present can then be removed with the aid of sodium hydrogen sulfite or by removing hydroxylamine hydrochloride. The organic solution is then with Using a suitable drying agent, e.g. anhydrous sodium sulfate, dried and freed from solvent. The remaining 2,2-dibromo-3-oxonitriles in most cases already have a degree of purity that allows the To put products directly into practical use. If desired, the Products purified by recrystallization or distillation in a thin film evaporator will.

Due to their microbistatic and microbicidal effect against The substances according to the invention are suitable for the solution for bacteria and fungi the various disinfection and preservation tasks in the non-therapeutic Area. For use as an active ingredient in antimicrobial agents, the inventive Substances are incorporated into liquid, pasty or solid preparations. Such means can be used in a wide variety of areas reach, for example as cleaning agents, disinfectants and preservatives for textiles, Floors, hospital facilities, medical instruments, schools, bathing establishments, public transport, commercial establishments such as dairies, and breweries Laundries.

The finished antimicrobial agents contain in addition to those described Active ingredients usually other commonly used ingredients, depending on the the previous.

see application form and the application purpose can be selected. For liquid preparations, water and common organic solvents are used as solvents Solvents, in particular alcohols and glycol ethers, optionally in a mixture with water into consideration. If in addition to the antimicrobial effect, an additional If cleaning action is desired, the agents can be nonionic surfactants or amphoteric surfactants contain. Addition products of 4 to 40, preferably, are used as nonionic surfactants 4 to 20 moles of ethylene oxide in 1 mole of fatty alcohol, alkylcyclohexanol, alkylphenol, fatty acid, Fatty amine, fatty acid amide or alkanesulfonamide are possible. Of special interest are addition products of 5 to 16 moles of ethylene oxide with coconut or tallow fatty alcohols, on oleyl alcohol and on mono-, di- or trialkylphenols and on monoalkylcyclohexanols with 6 to 14 carbon atoms in the alkyl radicals. The derivatives are used as amphoteric surfactants of secondary or tertiary aliphatic amines in question, the aliphatic Radicals can be straight-chain or branched and one radical has 8 to 18 carbon atoms and another a solubilizing anionic group, such as a carboxy, Sulfo, sulfato, phosphato or phosphono group contains.

Builder substances can also be present in the antimicrobial agents be; inorganic or organic salts, in particular inorganic salts, are suitable as such or organic complexing agents. For example, ortho-, pyro- and Tripolyphosphates of the alkali metals, the alkali salts of the complexing aminocarboxylic acids like nitrilotriacetic acid and ethylenediaminetetraacetic acid, the alkali salts of complexing agents Phosphonic acids such as l-hydroxyethane-l, l-diphosphonic.

acid, aminotrimethylene phosphonic acid and ethylenediaminetetramethylene phosphonic acid, as well as the alkali salts of sulfodicarboxylic acids, lactic acid, citric acid and tartaric acid. The acidic, water-soluble salts of higher molecular weight are also used as structural substances Polycarboxylic acids into consideration, such as polymers of maleic acid, itaconic acid, fumaric acid and citric acid. Copolymers of these acids with one another or with others polymerizable substances, such as ethylene, propylene, acrylic acid, vinyl acetate, Isobutylene, acrylamide and styrene are useful. When the antimicrobial agents contain organic solvents, the addition of solubilizers such as benzene, Toluene and xylene sulfonic acid in the form of their alkali salts should be indicated.

The content of substances according to the invention is in the ready-to-use -antimicrobial agents between 0.01 and 5 percent by weight, based on the total Middle. Concentrates can be used for the production of such ready-to-use agents or solid mixtures can be put together that contain up to 50 percent by weight of active ingredient contain.

The substances according to the invention can also be used for preservation of technical products that lead to bacterial and fungal attack or other microbial Tend to destruction, such as paste, glue, emulsion paints and cutting and drilling oils are used.

For this purpose, an addition of 0.01 is generally required up to 2 percent by weight, based on the material to be preserved, is sufficient.

EXAMPLE A. Preparation of the 2,2-dibromo-3-oxonitrile Example 1 In a stirring apparatus with stirrer, dropping funnel, gas inlet tube and attached In the distillation column, 130.2 g (1 Mol) of methyl caproate and 548 g (13.4 mol) of acetonitrile are heated to the boil. 180 g of 30 percent by weight were added to the boiling reaction solution in the course of 2 hours Sodium methylate solution (54 g = 1 mol of sodium methylate) was added dropwise. Simultaneously was Methanol originating from the sodium methylate solution and formed in the reaction distilled off together with acetonitrile via the distillation column. After the end the addition of the sodium methylate solution, the distillation was continued until until the boiling point of the pure acetonitrile was established in the top of the column and the The elimination of methanol was complete. A total of 640 g of distillate were obtained during the distillation obtained, which, according to gas chromatography, was 24.1 percent by weight from methanol and 75.9 percent by weight acetonitrile.

The sodium enolate salt which precipitates on cooling the reaction mixture the 3-oxooctanenitrile was separated off by filtration and washed with acetone. 134 g (83% of theory) of white salt were obtained.

To convert into the free 3-oxooctanenitrile, 27.6 g (0.17 Mol) of the sodium enolate salt in a mixture of 100 ml of ice water and 58 ml of 10 percent by weight Stir in hydrochloric acid and acidify to pH 4.

The 3-oxooctanenitrile which separated out was dissolved in methyl tert-butyl ether taken up, the separated organic phase was washed neutral with water and dried over sodium sulfate. After the methyl tert-butyl ether has been distilled off 22.5 g (932 d. Th.) 3-Oxooctanenitril remain, which after gas chromatography Analysis had a purity of 98 percent by weight.

In a stirred apparatus with stirring, ice cooling and introduction of nitrogen to 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 at 10 to 150 ° C in the course of 90 minutes 35.2 g (0.22 mol) of bromine dissolved in 40 ml of methylene chloride, added dropwise. The resulting mixture was used to complete Reaction 4 Stirred for hours at room temperature. Then the methylene chloride phase severed. 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 became over distilled in a thin film evaporator at 950C / 0.01 mbar. There were 22.1 g (75% of theory) 2,2-dibromo-3-oxooctanenitrile (substance A) as a yellowish oil with n20 = 1.5055 obtained which, according to gas chromatographic analysis, has a degree of purity of 97.2 percent by weight.

Analysis C8H11NOBr2 (MM 296.989) calcd (%): 32.35 C; 3.73 H t 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; CDCl3) = 3.10 (t); 1.75 (m); 1.35 (m) ; 0.90 (t) Substances B to E were produced in an analogous manner.

Substance B. 2,2-Dibromo-3-oxodecanenitrile yellowish oil with nD20 = 1.4978 ; Bp. 120 ° C / 0.01 mbar analysis C10H15NOBr2 (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: CDCl3) = 3.01 (t); 1.72 (m); 1.30 (m); 0.87 (t) 13 C-NMR spectrum (50 MH2; CDCl3) = 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 nD20 = 1.4956 analysis C12H190NBr2 (MM 353.096) calcd (%): 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-dibromo-3-oxotetradecanenitrile colorless crystals; Fp. 340C analysis C14H23ONBr2 (MM 381.15) calcd (%): 44.12 C, 6.08 H t 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-oxoeicosane nitrile, colorless crystals with melting point. 57 ° C analysis C20H35NOBr2 (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 t 33.7 Br.

Bëi's'pi'ël-2 'In a stirring apparatus with stirrer, dropping funnel, gas inlet tube and reflux condenser, 28.8 g (0.6 Mol) sodium hydride (as a 50 percent by weight suspension in white oil) in 200 ml of absolute Suspended toluene and added 49.9 g (0.3 mol) of 2-methoxybenzoic acid methyl ester. The mixture was heated to 850C. Over the course of 2 hours, 24.6 g (0.5 Mole) of absolute acetonitrile was added dropwise to the heated mixture. After that, the reaction mixture became Stirring was continued for 15 hours at 900C. The mixture was then cooled to OOC, 300 ml of ice water were carefully added with vigorous stirring and then for 1 hour for a long time at OOC. The aqueous phase was then separated off and extracted with 100 ml of toluene. After cooling to 0 ° C, the aqueous phase became acidified to pH 1 with dilute hydrochloric acid. The precipitated product was with Washed and dried ice water. The crude product (44 g) was made from isopropanol recrystallized; 37.9 g (72% of theory) of 2-methoxybenzoylacetonitrile were included M.p. 85-880C.

8.7 g (0.05 mol) of 2-methoxybenzoylactonitrile were dissolved in 70 ml of methylene chloride solved. After adding a solution of 20 g of potassium hydrogen carbonate in 100 ml of water the mixture was cooled to -50C before taking vigorously stir 17.6 g (0.11 mol) of bromine in 30 ml of methylene chloride were added dropwise over the course of 2 hours became. When the addition of bromine was complete, the reaction mixture was at for 90 minutes -5 to OOC. Excess bromine was then added by adding Removed hydroxylamine hydrochloride, separated the organic phase, twice with washed 100 ml of water and dried over magnesium sulfate. After evaporation of the solvent in vacuo remained 15.5 g (93% of theory) of 2-methoxybenzoyldibromoacetonitrile (Substance J) as yellow oil with 20 1.5948.

nD analysis C1OH7H02Br2 (MM 333.006) calculated (%): 36.07 C t 2.12 H t 4.21 N; 47.99 Br.

Found (%): 35.90 C t 1.97 H; 4.11 N; 47.80 Br.

1 H NMR spectrum (60 MHz; CDCl3) = 3.92 (s); 6.95 - 7.77 (m) IR (film) : 1730 cm-l Substances F to I and K to R were prepared in an analogous manner.

Substance F: Benzoyldibromoacetonitrile yellowish oil with n2DO = 1.5982 ; Bp. 1200C / 0.01 mbar (thin film evaporator) Analysis C9H5NOBr2 (MM 302.952) Calculated (%): 35.68 C; 1.66 H; 4.62 N; 52.75 Br.

found (%): 34.0 C; 1.5 H t 4.7 N; 53.8 Br.

H-NMR spectrum (60 MHz; CDCl3) = 8.19 (d, d); 7.59-7.33 (m) 13 C NMR spectrum (50MHz; CDCl3) = 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 oil with nD20 = 1.5949 analysis C10H7N0Br2 (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 nD20 = 1.5991 Analysis C10H7N0Br2 (MM 317.006) calculated (%): 37.89 C; 2.23 H; 4.42 N; 50.42 Br.

found (%): 38.20 C; 1.99 H t 4.38 N; 51.5 Br.

Substance I: 4-methylbenzoyldibromoacetonitrile colorless crystals; Fp. 65-690C analysis C10H7NOBr2 (MM 317.006) calcd (%): 37.89 C; 2.23 H; 4.42 N; 50.42 Br.

Found (%): 37.40 C t 2.11 H; 4.39 N; 50.40 Br.

Substance K: 3-methylbenzoyldibromoacetonitrile yellowish oil with nD20 = 1.6048 analysis C10H7NOBr2 (MM 317.006) calcd (%): 36.07 C t 2.12 H; 4.21 N; 47.99 Br.

found (%): 36.00 C; 2.07 H; 4.26 N t 48.8 Br.

Substance L: 4-methoxybenzoylbromoacetonitrile colorless crystals; Fp 57-620C analysis C1OH7N02Br2 (MM 333.006) calcd (%): 36.07 C; 2.12 H t 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 nD20 = 1.5966 analysis C9H4NOBr2C1 (MM 337.428) calcd (%): 32.04 C; 1.19 H; 4.15 N; 47.37 Br 10.51 C1.

found (%): 31.6 C; 1.03 H; 4.50 N; 46.00 Br 10.0 C1.

Substance n: 3-chlorobenzoyldibromoacetonitrile yellowish oil with nD20 = 1.6092 Analysis CgH4NOBr2Cl (MM 337.428) calculated (%): 32.04 C; 1.19 H t 4.15 N t 47.37 Br 10.51 C1.

found (%): 31.7 C; 1.25 H; 4.18 N; 46.5 Br 10.50 C1.

Substance O: 4-chlorobenzoyldibromoacetonitrile colorless crystals; Fp. 41-420C analysis C9H4NOBr2Cl (MM 337.428) calcd (%): 32.04 C; 1.19 H; 4.15 N; 47.37 Br 10.51 C1.

found (%): 31.17 C; 1.19 H; 4.06 N; 47.20 Br 10.1 Cl.

Substance Q: 4-bromobenzoyldibromoacetonitrile colorless crystals; Fp. 38-440C analysis CgH4NOBr3 (MM 381,887) calculated (%): 28.31 ° C ; 1.06 H; 3.67 N t 62.78 Br.

found (%): 27.90 C; 0.96 H; 3.66 N; 61.90 Br.

Substance Q: 1-naphthoyldibromoacetonitrile colorless crystals; Fp. 48-51 ° C analysis C13H7NOBr2 (MM 353.036) calculated (%): 44.23 C; 2.00 H t 3.97 N; 45.27 Br.

found (%): 43.20 C; 1.91 H t 3.80 N; 44.8 Br.

Substance R: 2-naphthoyldibromoacetonitrile colorless crystals; Mp 61-67 ° C Analysis C13H7NOBr2 (MM 353.036) calcd (%): 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 prepared according to Examples 1 and 2 are summarized in Table I below together with their physical data.

TABLE I 2,2-dibromo-3-oxonitriles of the formula R-CO-CBr2-CN Substance RI bp. Mp n20 (OC / mbar) (OC) D. AA n-C5H11 95 / 0.01 oil fi 1.5055 BB n-C7H15 1 120 / 0.01 oil 3 1.4978 CC n CgHl9 oil '1.4956 DD n-C11H23 t 34 E. C17H35 17E35 - ~ 57 - F 1 120 / 0.01-1.5982 G <C 3 oil 1.5949 X CH3, H 1 - oil 1.5991 I. -CH - 65-69 1 - J OCH3, - oil. 1.5948 K v C 3l oil 1.6048 ¼ ¼ PCH, L pOCH3 - 57-62 - TABLE I (continued) 2,2-Dibromo-3-oxonitriles of the formula R-CO-CBr2-CN n20 Substance R bp. M.p. : i (OC / mbar) (OC) M jül; - oil 1.5966 IN N i ffi C1 'oil 1.6092 I ¼ cycl 41-42 I. Bri I P p, g ~ 38-44 ¢ - QQ <~ t 48-51 RR; <Y - 61-67 B. Antimicrobial activity I. Microbistatic activity The microbistatic activity of substances A to R according to the invention was determined against the following test germ suspensions: 1. Staphylococcus aureus 2 x 109 germs / ml 2. Escherichia coli 2 x 109 germs / ml 3. Pseudomonas aeruginosa 5 x 108 Germs / ml 4. Candida albicans 2 x 108 germs / ml 5. Aspergillus niger 5 x 107 germs / ml 6. Penicillium camerunense 5 x 107 germs / ml The inhibitory concentrations of the compounds to be examined were determined using the dilution test according to the guidelines for the test chemical disinfectants determined by the German Society for Hygiene and Microbiology (1972). The experiments were carried out in sterile test tubes which contained standard I broth (pH 7.5 Merck) for germs 1 to 3 and wort broth (pH 5.5, Merck) for germs 4 to 6. After the addition of the active ingredients, the volume of the nutrient solution in each of the tubes was 5 ml. Subsequently, 0.1 ml of the test microbe suspension of the specified concentration was placed in each of the tubes. The nutrient solution samples inoculated with bacteria were stored in an incubator at 37 ° C. for 3 days. The specimens inoculated with fungi were incubated at 30 ° C. for 4 days. It was then determined which concentration of active substance added to the nutrient medium had barely 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.

For substances A to R, those in the table below were used II reproduced inhibitory concentrations determined.

TABLE II Homm concentrations (in ppm) of substances A to Q in the dilution test Test germ substance 1 2 3 4 5 6 A 50 100 100 50 50 50 B '50 100 100 50 50 C10 C 50 100 100 50 50 50 D 50 100 100 50 50 50 E. F 100 50 50 50 # 10 # 10 G ç 100 1 250 500 100 | 50 50 H 100 100 100 50 # 10 # 10 I 100 100 100 50 50 50 J 100 250 100 50 50 50 K 100 100 100 50 50 50 L 100 | 100 100 50 50 | 50 M; 250 | 250 250 50 50 | 50 N 50 100 50 50 # 10 # 10 O P 100 100 100 50 50 50 Q | 250 | 500 500 100 50 50 R | 100 | 100 100 100 | # 10 | # 10 | 2. ' Microbicidal effectiveness The microbicidal effectiveness of substances A to R according to the invention was determined against the following test germ suspensions: 1. Staphylococcus aureus 2 x 109 germs / ml 2. Escherichia coli 2 x 109 germs / ml 3. Pseudomonas aeruginosa 5 x 108 germs / ml 4. Candida albicans 2 x 108 germs / ml 5. Aspergillus niger 5 x 107 germs / ml 6. Penicillium camerunense 5 x 107 germs / ml The killing times of the products to be examined were determined with the aid of the suspension test. Using water with a hardness of 170 dH, test solutions were prepared which contained 2000 or 500 ppm of active ingredient. At room temperature, 0.1 ml of test germ suspension was pipetted into test tubes and mixed with 10 ml of each of the test solutions described above. After different exposure times of up to 60 minutes, approx. 0.05 ml of material was removed from the test tubes with the aid of an inoculation loop and spread on a nutrient agar containing 38 Tween 80 and 0.38 lecithin as an inhibitor. The nutrient medium for germs 1 to 3 consisted of 2.5 percent by weight standard I broth (Merck) and for germs 4 to 6 of wort broth pH 5 (Merck), each of which contained 1.2 percent by weight agar for solidification. The samples were incubated at 370C and 300C, respectively. After 2 to 3 days, the cultures were assessed macroscopically for growth and in this way the killing time or the residual germ content was determined. The results found are shown in Table III below.

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

TABLE III Death times of substances A to Q in the suspension test Sub-conc. Test germ punch (ppm) 1 2 3 4 5 6 A 200 # 15 # 15 # 15 # 15 # 15 # 15 500 # 15 60 60 # 15 # 15 60 B 2000 # 15 # 15 # 15 # 15 # 15 # 15 500 # 15 60 60 60 # 15 60 C 2000 # 15 # 15 # 15 # 15 # 15 # 15 500 # 15 60 # 15 # 15 # 15 60 D 2000 # 15 +++ 60 60 60 500 60 +++ E. F 2000 # 15 # 15 # 15 # 15 # 15 # 15 500 + 60 # 15 60 60 60 G 2000 60 +++ 60 60 ++ +++ 500 + +++ +++ +++ +++ +++ H 2000 60 60 # 15 # 15 60 # 15 500 +++ ++ 60 ++ +++ +++ I 2000 60 60 # 15 60 60 ++ 500 + ++ 60 ++ ++ +++ TABLE III (continued) Sub-conc. Test germ punch (ppm) 1 2 3 4 5 6 J 200 60 60 # 15 # 15 60 # 15 500 +++ +++ + +++ +++ +++ K 2000 ++ 60 # 15 60 + / 15 500 +++ +++ +++ +++ +++ L 2000 +++ 60 # 15 60 60 500 +++ + 60 ++ ++ M 2000 60 60 # 15 60 60 500 +++ ++ 60 +++ +++ N 2000 # 15 # 15 # 15 # 15 # 15 60 500 ++ 120 120 120 120 ++ 0 2000 500 P 2000 60 60 # 15 # # 15 60 500 +++ ++ 60 60 +++ Q 2000 415 60 60 60 ++ 500 60 60 60 60 ++ R 2000 # 15 # 15 # 15 # 15 # 15 ++ 500 # 15 # 15 # 15 # 15 60 +++

Claims (2)

P a t e n t a n s p r ü c h e 1. Use of 2,2-dibromo-3-oxonitriles of the formula I, R - CO - CBr2 - CN (I) in which R is in each case an optionally substituted one represents aliphatic, cycloaliphatic, aromatic or heterocyclic radical, as antimicrobial agents. 2. Use of 2,2-dibromo-3-oxonitriles according to claim 1, characterized characterized in that in the formula I R is a straight-chain or branched alkyl radical with 3 to 21 carbon atoms, one optionally substituted by alkyl radicals cycloaliphatic radical with 3 to 6 ring hydrocarbon atoms, one optionally phenyl or phenyl groups substituted with alkyl groups, alkoxy groups, halogen atoms or nitro groups Naphthyl radical or a five- or six-membered oxygen, sulfur or nitrogen atom represents containing heterocyclic radical.