DE967121C - Germicidal preparation - Google Patents

Description

FEDERAL REPUBLIC OF GERMANY

ISSUED OCTOBER 3, 1957

GERMAN PATENT OFFICE

PATENT LETTERING

CLASS 3Oi GROUP 3 INTERNAT. CLASS A 611

G I00I2 IVa / 30 i

Dr. Guido Schetty, Walter Stammbach and Dr. Ernst Model, Basel (Switzerland)

have been named as inventors

JR Geigy A.-G. _r Basel (Switzerland)

Germicidal preparation

Patented in the territory of the Federal Republic of Germany on December 28, 1952

Patent application published August 30, 1956

Patent issued September 19, 1957

The priority of the application in Switzerland of December 29, 1951 has been claimed

The invention relates to the production of a new, highly effective germicidal preparation.

It has been found that by condensation of 4-halo-i-oxybenzenes which are in the 3-position are further substituted by a halogen atom or the trifluoromethyl group, with formaldehyde or these dispensing agents according to methods known per se to new 2, 2'-dioxydiphenylmethane compounds general formula can arrive.

OH

HO

CH, -

Shark

Hal

In this formula, in both benzene rings, Hai denotes halogen and X denotes halogen or the trifmomethyl

These new 2, 2'-dioxy <üphenylmethanverbindun- ao genes have an excellent germicidal effect and stand out from known similar compounds through a superior range of effects.

In the 4-halogeno-i-oxybenzenes according to the above definition, halogen substituents can be used For economic reasons, chlorine atoms are preferred, but bromine atoms may also be used. As" suitable phenols are: 3, 4-dichloro-oxybenzene, 3,4-dibromo-i-oxybenzene, 3-chloro-4-bromo- and 3-bromo-4-chloro-i ~ oxybenzene and in particular s-trifluoromethyl ^ -chloro-i-oxybenzene.

709 701/5

The condensation of the 4-halophenols which can be used by definition with formaldehyde or these The release agents are carried out according to methods known per se, for example in concentrated sulfuric acid in the presence or absence of organic solvents and diluents, such as lower alcohols. Preferred formaldehyde or formaldehyde-releasing agents are those concentrated aqueous solutions or paraformaldehyde in question.

No protection is sought for the production of the compounds in the present description.

The 2, 2'-dioxydiphenyhnethane derivatives according to the invention are white, well-crystallized, odorless Powders with a mostly defined melting point, which are little in water, but good in lower alcohols and ketones, such as ethyl alcohol or acetone, dissolve. Their monoalkali salts are little in cold water, their dialkali salts, on the other hand, are readily soluble. These new diphenylmethane compounds are used for disinfection purposes Solutions or suspensions in liquids produced, for example in detergents, Ointment bases, creams, etc. can be incorporated.

Compared to the known halogenated oxydiphenylmethane compounds, which do not have the substitution according to the definition, show those according to the invention new diphenylmethane derivatives have the advantage of increased effectiveness and in particular a superior range of effects, as they are also effective against certain gram-negative bacteria. Furthermore, they are also more effective fungicidally.

It is known from Chem. Zentralblatt 1932, II, p. 3231, and US Pat. No. 1 967 825 that halogen derivatives of monooxydiphenyhnethane have an antibacterial effect. Furthermore, the germicidal effectiveness of some halogenated 2, 2'-dioxydiphenylmethane compounds is known; so for the 2, 2'-dioxy-5, 5'-dichlorodiphenylmethane from the Swiss patent specification 220 596 and the Belgian patent specification 496 622, for the 2, 2'-dioxy-3. 5> 6, 3 ', 5'. ö'-hexachlorodiphenylmethane from US Pat. No. 2,435,593 and Belgian Pat. No. 496,622 and for 2,2'-dioxy-3, 4, 5, 6, 3 ', 4', 5 ', ö'-octachlorodiphenylmethane from U.S. Patent 2,353,725.

The table below shows results obtained with the compounds according to the invention 2, 2'-dioxy-4, 5, 4 ', 5'-tetrachlorodiphenyl methane and 2, 2'-Dioxy ~ 4, 4'-bis-trifluoromethyl-5, 5'-dichlorodipheiiyhnethane compared with similar data for the known halogenated ones mentioned above Oxydiphenyhnethanverbindungen.

In order to obtain these results, the minimum concentration of the disinfectant that a standard suspension of test germs will definitely kill under certain conditions in bacteria (bactericidal activity) or the growth of pikes with certainty suppressed (fungistatic activity) was adjusted with graduated concentrations the principle of the dilution method is determined and expressed as 10- ⁶ mole.

Bacteriological test

The standard suspension is a washing away of the test germs from 10-hour agar cultures with sterile tap water, the density of which is set to 85% light transmission in the so-called »BIO-PHOTO-COLtf apparatus from Hellige. The standard suspension is mixed with equal parts of graduated dilutions of the disinfectants to be tested (in aqueous solutions). Exposure time: 10 minutes; Temperature: 20 ⁰ C.

At the end of the action, two subcultures of each reaction mixture are made in glucose broth created. The subcultures are incubated at 37 °. The development or sterility of the subcultures is determined after 48 hours.

Mycological examination

Sabouraud maltose agar (Difco), which contains the chemical compound to be tested in graduated concentrations, is used as a mycological culture medium. The solidified Schrägagarnährböden are inoculated with an aqueous bacterial suspension and incubated at 30 ⁰ C. The development or sterility of the cultures is determined after 10 days.

Table germicidal effectiveness

link Penicil Cteno- Salmo
_ 11- Salmo
i-iöiio Boar- Escher Staphylo No. lium myces Hella.
bulkhead neiia
enteri- thella ischia coccus 2, 2'-dioxy-4, 5, 4 ', 5'-tetrachloro species interdig. mülleri tidis thyphosa coli " aureus I. diphenylmethane 2, 2'-Dioxy-4, 4'-bis-trinuOTBEtethyl- 3, i 1.6 246 164 164 109 3, i 2 5,5'-dichlorodiphenyhnethane 4'-chloro-4-oxy-diphenyhnethane 3, i 1.6 370 370 370 246 1.6 3 3-ChlQr-4-oxy-diph.enylmeth.an 250.0 5o, o 833 833 833 833 555.0 4th 5-chloro-2-oxy-diphenylmethane 250.0 25.0 1250 1250 1250 833 370.0 5 250.0 25.0 833 555 833 555 250.0

No. link Penicil effectiveness Salrao- SalmO- Boar- Escher 65 Staphylo 80 3.1 85 lium Cteno- Hell El
schott ™ ΘΙ1ΪΒΓΪ ~ thella ischia coccus Tabel 6th 4 ', 3-dichloro-4-oxydiphenylmethane species myces mülleri tidis thyphosa coli aureus
70 6.2 Germicides 7th 4 ', s-dichloro ^ -oxydiphenylmethane 250.0 interdig. X X 1250 I250 125.0 8th 4 ', 4, s-trichloro ^ -oxydiphenyl- 125.0 12.5 555 X 833 1250 125.0 methane 12.5 9 4 '»5'> 4» S-tetrachlor-z-oxy- 500.0 833 1250 833 555 25.0 ₇₅ diphenylmethane 6.2 IO 2, 2'-dioxy-5, 5'-dichloro 500.0 1250 1250 37 ° 833 12.5 diphenylmethane 6.2 II 2, 2'-dioxy-3, 5, 6, 3 ', 5', 6'-hexa- 100.0 555 555 555 246 100.0 chlorodiphenylmethane 12.5 12th 2, 2'-dioxy-3, 4, 5, 6, 3 ', 4', 5 ', 6'- 6.2 X 833 833 833 octachlorodiphenyl methane 3.1 500.0 X X 833 1250 X = no bactericidal effect at 1250 χ io ~ ⁶ mol. 125.0

It follows from the table above that the halogenated 2, 2'-dioxydiphenylmethane compounds according to the invention in comparison with known halogenated Oxydiphenylmethane compounds are characterized by better bactericidal and fungistatic effectiveness, by having a much smaller effective limit concentration in the test germs listed above exhibit. The halogenated monooxydiphenylmethane compounds (Nos. 3 to 9) are particularly much less effective against Penicillium species, Escherischia coli and Staphylococcus aureus. Further the compounds according to the invention stand out in comparison with 2,2'-dioxy-5, 5'-dichlorodiphenylmethane (No. 10) in particular through their action against Penicillium species and Staphylococcus aureus, in comparison with the 2, 2'-dioxy-3, 5, 6, 3 ', 5', 6'-hexachlorodiphenylmethane (No. 11.) by their effect against Salmonella schottmülleri and Escherischia coli and in comparison with the 2, 2'-dioxy-3, 4, 5, 6, 3 ', 4', 5 ', 6'-octachlorodiphenylmethane (No. 12) by their action against Penicillium species and Escherischia coli.

The new diphenylmethane compounds can be prepared according to those shown below, for example Working methods are presented.

example 1
OH OH

16.3 parts of 3,4-dichloro-i-phenol are dissolved in 16 parts of methanol; this solution is added dropwise to 250 parts of 80% sulfuric acid at 0 to 5 ° over the course of 3 hours. Subsequently, 1.5 parts of formaldehyde (as an approximately 40% solution) are ^{added dropwise at from 0 to} 50 over the course of 6 hours, after which the mixture is stirred for 24 hours at 5 to 10 °. The reaction mixture is then poured onto ice. The body which precipitates out is isolated, washed with water and dissolved as a disodium salt in dilute sodium hydroxide solution. This solution is freed from less resinous by-products by filtration and acidified with hydrochloric acid. The body which precipitates out as a powder is filtered off, washed neutral with water, dried and recrystallized twice from benzene. A white, crystalline powder with a melting point of 194 to 196 ^{° is obtained in this way} .

C ₁₃ H ₈ O ₂ Cl ₄

Calculated: C 46.2, H 2.39, Cl 42.0 ° / ₀ ,
found: C 46.0, H 2.64, 0141.7%.

Example 2

16.3 parts of 3,4-dichloro-i-phenol are dissolved in 65 parts of glacial acetic acid and slowly added dropwise at 0 ° to 5 ° into 160 parts of 93% strength sulfuric acid. Are then added 1.5 parts of formaldehyde (as a 40% aqueous solution) at längsam ο to 5 ⁰ to and then stirred for a further 16 hours at 5 to 10 °. It is poured onto ice and worked up as indicated in Example 1. A white, crystalline powder with a melting point of 194 to 196 ^{° is obtained} .

Example 3
OH OH

Cl Cl

19.7 parts of s-trifluoromethyl ^ -chloro-i-phenol become dissolved in 200 parts of 93% strength sulfuric acid. In these

Solution is allowed to drop in 4.1 parts of a 37% strength aqueous formaldehyde solution at 5 to 10 ° in the course of 5 to 6 hours. Thereafter, the mixture is stirred for 20 hours while allowing to rise the temperature to 20 ^0, the reaction mass is poured onto ice, isolated the precipitated resinous body and subjected to distillation with water vapor. The unchanged trifluoromethylchlorophenol passes over with the steam. The condensation product freed from the starting material in this way is dissolved in 200 parts of water with sodium hydroxide solution as the disodium salt, freed from resinous by-products and acidified with hydrochloric acid. The condensation product obtained is still impure. It is therefore recrystallized from benzene, white crystals with a melting point of 181 ° to 182 ° being obtained.

C ₁₅ H ₈ O ₂ Cl ₂ F ₆

Calculated: C 44.4, H 1.99, Cli 7.5 ° / ₀ ,
found: C 44.4, H 1.97, Cl 17.5%.

Claims (4)

Patent claims: i. Germicidal preparation containing halogenated 2,2'-dioxydiphenylmethane, characterized in that that these of the general formula OH HO Shark Shark correspond, in which in both benzene rings Hai is halogen and X is halogen or the trifluoromethyl group means. 2. Germicidal preparation according to claim i, characterized in that it contains a cleaning agent is united. 3. Germicidal preparation according to claim 1, characterized in that it is with an ointment base or a cream is combined. 4. Germicidal preparation according to claim 1, characterized in that it is mixed with a known cosmetic is presented. ' Considered publications:
Chem. Zentralbl. 1932, II, p. 3231;
U.S. Patents Nos. 1,967,825, 2,435,593, 353,725; Swiss Patent No. 220 956;
Belgian patent specification No. 496 622. © 609 616 / 4.11 8.56 (T09 701/5 9.57)