DE2538771A1 - Antimicrobial agents contg. (2)-furanone derivs. - used e.g. as cleansing agents and disinfectants for textiles, hospital equipment, breweries and bathing pools - Google Patents

Abstract

New antimicrobial agents contain lactone derivs. of formula (I). In this formula, R is OH, halogen, lower alkoxy or lower acyl; and R1 and R2 are H, halogen or lower alkyl. (I) have good inhibitory activity on bacteria and fungi. They can be used e.g. as cleansing agents and disinfectants for floors, wood and plastic surfaces, plants such as laundries and bathing pools. (I) are partic. suitable in textile and surface disinfection. A typical surface disinfectant spray formulation contains 5 pts. wt. (I; R=Cl, R1=R2=H), 0.5 pts. wt. perfume, 45 pts. wt. ethanol, and propellant gas =100 pts. wt.

Description

"Antimicrobial Agents" The invention relates to antimicrobial agents with a content of substituted (5H) -furan-2-ones.

It has been found that antimicrobial agents containing compounds of the formula in which R is a hydroxy, halogen, lower aloxy or lower acyl group and R¹ and R² can be the same and different and represent hydrogen, halogen or a lower alkyl group, have good antimicrobial activity.

Accordingly, in the antimicrobially active agents according to the invention For example, the following compounds are used: 5-hydroxy- (5H) -furanone- (maleic aldehyde acid), 3,4-dichloro-5-hydroxy- (5H) -furanone-2 (mucochloric acid), 3,4-dibromo-5-hydroxy- (5H) -furanone-2 (mucobromic acid), 3-chloro-4-bromo-5-hydroxy- (5H) -furanone-2, 3-bromo-4-chloro-5-hydroxy- (5H) -furanone-2, 3,4-dimethyl-5-hydroxy- (5H) -furanone-2, 3-methyl-4-ethyl-5-hydroxy- (511) -furanone-2, 4-ethyl-3-methyl-5-hydroxy- (5H) -furanone-2, 5-chloro- (5H) -furanone-2, 3,4,5-trichloro- (5H) -furanone-2, 5-bromo- (5H) -furanone-2, 3-methyl-4-ethyl-5-bromo- (5H) -furanone-2, 5-methoxy- (511) -furanone-2, 5-ethoxy- (5H) -furanone-2, 5-isopropyloxy- (5H) -furanone-2, 5-butoxy- (5H) -furanone-2, 5-acetyl- (5H) -furanone-2, 3,4-dichloro-5-acetyl- (5H) -furanone-2 or 5-propionyl- (5H) -furanone-2.

The substituted (5H) -furan-2-ones are known per se from the literature Compounds, their preparation is carried out by generally known processes, for example by G.O. Schenck in Liebig's Annalen der Chemie (1966) Volume 697, page 42 ff.

and I.L. Doerr and R.E. Willette in the Journal of Organic Chemistry (1973), Volume 38, page 3878 ff. Have been described.

The agents according to the invention with a content of substituted (5H) -furan-2-ones have a good inhibiting effect on bacteria and fungi. You can do a variety of things Areas of application, for example, as cleaning and disinfecting agents for textiles, floors, wood and plastic surfaces, hospital furnishings and commercial operations such as breweries, laundries and bathing establishments.

The agents according to the invention have proven to be very advantageous in Textile and surface disinfection proven. The means can be liquid, paste-like or solid preparation form, but can also be used as sprays.

The content of compounds of the formula I in the antimicrobial agents can vary within wide limits, but is usually between 0.1 and 80 percent by weight, in the case of textile and surface disinfectants, the content can e.g. B. from 0.1 to 10 Percent by weight, preferably 1 to 7 percent by weight, based on the total agent be.

The agents according to the invention also contain, depending on their use further constituents known per se and familiar to the person skilled in the art.

The following examples are intended to further improve the subject matter of the invention explain without, however, limiting it to them.

Examples A) Preparation: Example 1 A solution of 90.5 g (0.94 Mole) of freshly distilled furfural and 1.3 g of pink bengal in 850 ml of absolute ethanol was initiated by introducing a strong stream of oxygen by means of a 1000 W UV lamp photolyzed.

The temperature was kept at 250-30 ° C. by cooling. Of the The degree of reaction could be determined with the help of IR absorption measurements. After approx.

The photolysis was complete for 6 hours and the solvent was distilled off. After adding 150 ml of carbon tetrachloride, a crystalline residue was obtained. which was filtered off. The yield of substance A (maleic aldehyde acid) was 36 g, corresponding to 39% of theory. Melting point: 550C.

Example 2 In a two-necked flask with a stirrer, 10 g (0.1 mol) Submitted malealdehyde and at room temperature 12 g (0.1 mol) of thionyl chloride added dropwise. The mixture was then stirred at about 40 ° C. for 3 hours. Substance B (maleic aldehyde pseudochloride, see Tab. 1) was purified by distillation in a water jet vacuum (approx. 15 torr).

4.8 g, corresponding to 41% of theory, were obtained.

Boiling point: 92 ° C / 15 torr.

Example 3 In the same structure as in Example 2, 10 g (0.1 Mol) maleic aldehyde and 17.3 g (0.2 mol) of acetyl chloride reacted. It was 2 Hours at approx.

80 ° C then stirred. The distillation of the resulting product C (maleic aldehyde pseudoacetate, see Table 1) in a water jet vacuum gave a yield of 9 g (63% of theory). Boiling point: 125 ° C / 15 torr.

Example 4 27 g (0.27 mol) of maleic aldehyde acid, 0.5 ml of acetyl chloride and 150 ml of methanol were refluxed for 4 hours.

The methanol was then distilled off and the product D (maleic aldehyde pseudomethyl ester, see Table 1) purified by distillation. Yield: 4 g (14% of theory), boiling point: 910C / 15 torr.

B) Use: Example 5 To determine the antimicrobial effectiveness the substituted (5H) -furan-2-ones has the inhibitory effect on the following test germs certainly.

1) Staphylococcus aureus (5 x 107 germs per ml) 2) Escherichia coli (4 x 107 germs per ml) 3) Pseudomonas aeruginosa (4 x 107 germs per ml) 8 4) Candida albicans (108 germs per ml) 8 5) Aspergillus niger (108 germs per ml) 8 6) Mucor plumbeus (108 germs per ml) The inhibitory concentrations of the products to be examined were made using the dilution test according to the guidelines for testing chemical Disinfectants, published by the German Society for Hygiene and Microbiology (1959). The desired test concentrations were made by mixing measured amounts of the substance solutions of suitable concentrations made with broth in sterile tubes, the total volume of each 10 ml was. The tubes were then filled with 0.1 ml of the test microbial suspension mentioned Inoculated concentrations of germs. The inoculated tubes were incubated for 3 days at 370C incubated.

The substance concentration added to the nutrient medium was then determined was just able to completely prevent the growth of the germs. This so determined The value was referred to as the inhibitory concentration.

The tests were carried out at the following concentration intervals: 1,000 ppm, 750 ppm, 500 ppm, 250 ppm, 100 ppm, 50 ppm, 25 ppm and 10 ppm.

In this dilution test, those in the table below were used 1 listed inhibitory concentrations for the individual products for the aforementioned Germs determined.

Table 1 Dilution test, inhibitory concentrations in ppm Conn- R R1 R2 St. E. Ps. Cand. Asp. Mucor dung aureus coli aerug. silly niger plumbeus A OH HH 1000 1000 1000 1000 ~ 1) ~ 1) B Cl HH 1000 500 500 10 50 <10 O # C OC-CH3 HH 1000 1000 1000 100 100 50 D O-CH3 HH 1000 1000 1000 500 ~ 1) ~ 1) E OH Cl Cl 500 500 1000 1000 ~ 1) ~ 1) ~ 1) not determined The table shows the inhibitory effect of the compounds, especially against fungi.

Example 6 Furthermore, the inhibitory effect of the substances A to D in Agar hole test determined. For this purpose, Petri dishes with a diameter of about 9 cm were used Add 10 ml of bouillon or wort agar and apply a spatula to the surface inoculated with the test germs 1 - 4 (see example 5).

A 10 mm diameter hole was made in the center of the bowl Punched out nutrient medium and loaded with concentrated substance. The reading of the Results came after 24 hours.

The numbers in Table 2 indicate the width of the inhibition zone measured in millimeters from the edge of the hole to the area of uninhibited growth.

Explanation of symbols: O = no inhibition zone, uninhibited growth kW = no growth, complete inhibition Numbers = inhibition zone width in mm Table 2 Hole test, inhibition zone width in mm Conn- St. E. Ps. Cand. dung aureus coli aeruginosa albicans A 19 15 18 10 B KW KW KW KW C KW KW KW KW D KW KW 28 KW The results in the hole test show a very good inhibitory effect of the tested substituted (5H) -furan-2-ones.

Example 7 The antimicrobial effect of the substances investigated from the gas phase. For this purpose, Petri dishes were about halfway up Fill the height with nutrient broth and apply the test germs to the surface by spatula inoculates. In the lid of the Petri dish, a straight fit was made Filter paper loaded with the substance to be examined is inserted. The filter paper had no contact with the culture medium, but was about 5 - 6 mm above. The paper was loaded with 0.5 ml of each Solution of the substance to be examined in acetone. The after evaporation of the solvent Amounts of substance remaining on the filter paper were determined with the aid of the known Concentrations determined. The entire observation period to determine the hemin effect was 4 - 5 days. The results are summarized in Table 3.

Table 3 Inhibitory effect from the gas phase Substance amount staph. Pseud. (mg) aureus aerug. 25 KW KW B 10 + KW 5 ++ + 2.5 0 0 50 KW KW C 25 KW ++ 10 0 0 100 KW KW D 50 0 KW 25 0 ++ 10 0 0 Explanation of symbols: "KW" = no growth, complete inhibition + = growth in individual places ++ = growth in several places O = no inhibitory effect The table above shows the good inhibitory effect of substances from the gas phase, which are essential, for example, in textile and surface disinfection Can be found.

Example 8 Containing Some Antimicrobial Agents of substituted (5H) -furan-2-ones are described in the examples below.

Surface disinfectant spray substance B 5.0 parts by weight perfume 0.5 Ethanol 45.0 propellant to 100.0 surface disinfectant for hospitals nonylphenol + 9 ethylene oxide 4.0 parts by weight phosphoric acid 80% 5.0 formaldehyde solution 35% 20.0 substance D 2.5 water to 100.0 Antiseptic detergent for laundries sodium coconut fatty alcohol sulfate 10.0 parts by weight sodium tripolyphosphate 32.0 lt water glass 5.0 sodium carboxymethyl cellulose 1.0 "substance C 7.0 sodium sulfate and / or water to 100.0

Claims (2)

Claims 1. Antimicrobial agents containing compounds of the formula in which R denotes a hydroxy, lower alkoxy or lower acyl group and R1 and R2 can be identical and different and represent hydrogen, halogen or a lower alkyl group. 2. Antimicrobial agents according to claim 1, characterized by a Content of compounds of the formula 1 from 0.1 to 10 percent by weight, preferably 1 to 7 percent by weight based on the total antimicrobial agent.