DE913168C - Process for the production of bactericidal substances - Google Patents

Description

Process for the preparation of bactericidal substances The invention relates to the preparation of new bisbiguanides which have bactericidal properties. in which A denotes a phenyl radical which is substituted by an alkyl, alkoxy, nitro or halogen group, and in which the two A's can be the same or different, while n is an integer from 3 to 9 inclusive and the polymethylene The new bactericidal substances have the following general formula: chain can be interrupted by oxygen atoms and / or aromatic nuclei.

According to the invention, the new bactericidal substances can be prepared by a) a Polymethyienbisdicyandiamid of the formula where n has the value 3 to 9, with one or more amines of the formula A - N H., in a molar ratio of i: 2, where A is the has the meaning given above, or b) a polymethylenediamine of the formula H, N - [CH,] "- NH, where A denotes a halogen-substituted phenyl radical, have a very high bactericidal activity when tested under glass against the following organisms: Streptococcus haemolyticus, Staphylococcus aureus, Bacillus coli, Clostridium welchii and Pseudomonas pyocyanea.

Because of their high level of bactericidal activity, the new substances are useful for a variety of purposes, e.g. B. in medical and surgical practice, for the sterilization of instruments or bandages, as an addition to wood pulp to prevent the deterioration due to the development of fungi and bacteria, as an additive getting produced. It was found that compounds of the formulas and which are said to be useful as agents against malaria and are also effective against bactericides to a certain extent. It was found that (n = 3 to 9) is reacted with a dicyandiamide of the formula A-NH-C (: NH) -NH-CN in a molar ratio of i: 2.

As already stated, the new substances can be used as bactericides. It was z. B. found that those of the new substances containing the formula rubber latex, also as a preventive measure, and to control the sludge in paper mills. They can still be used as moth repellants for textiles.

In the German patent 620 509 diguanidines were described, ie compounds of the formula while according to the invention compounds of the formula have no activity against Streptococcus pyogenes and against Bacillus coli.

Biguanides are often described in US Pat. No. 2,500, for example the formula compounds according to the present invention, for example the formula in comparison to the compounds of the USA Patents 3 to 9 times against Streptococcus pyogenes and 27 to 8 times against Bacillus coli are more effective. the compounds according to the invention have a notable superiority as bactericides; It was found that the activity of the bisbiguanide of the French patent is only 1/3 to 1/9 against B. coli and 1/3 against Pseudomonas pyocyanea of the activity of the compounds according to the invention.

The invention is illustrated in the following examples, on which however, it is not limited. The parts are parts by weight.

Example i 25 parts of hexamethylene bis-dicyandiamide, 35 parts of p-chloroaniline hydrochloride and 250 parts of ß-ethoxyethanol are refluxed at 13o to 14o ° for 2 hours stirred together. The mixture is then cooled and filtered and the solid residue washed with water and crystallized from 500% aqueous acetic acid. i, 6-Di- (Nl, Nl'-p-chlorophenyldiguanid-N5, N5 ') - hexanedihydrochloride is colorless Obtained plates with a melting point of 258 to 26o °.

Example 2 19.4 parts of p-chlorophenyl dicyandiamide, 9.4 parts of hexamethylene diamine dihydrochloride and 100 parts of nitrobenzene are stirred together for 6 hours and heated to 150 to 160 ° warmed up. The mixture is cooled, diluted with zoo parts benzene, and filtered. The solid residue is washed with benzene and crystallized from 500% acetic acid. i, 6-Di- (NI, Nl'-p-chlorophenyldiguanid-N5, N5 ') - hexane dihydrochloride is obtained, which is identical to that described in example i.

Example 3 25 parts of hexamethylene bis-dicyandiamide, 29 parts of p-toluidine hydrochloride and 250 parts of ß-ethoxyethanol are put together on the reflux condenser for 2 hours at 14o ° stirred and heated. The mixture is then filtered and the solid residue with Washed ethanol and crystallized from aqueous ß-ethoxyethanol, where i, 6-di (NI, NI'-p-tolyldiguanid-Nb, N, ') - hexane dihydrochloride in colorless crystals with a Melting point of 263 to 264 ° is obtained.

Similarly, i, 6-Di- (N "Nl'-p-anisyldiguanid-N5, NS ') -hexanedihydrochloride from hexamethylene bis-dicyandiamide (25 parts) and p-anisidine hydrochloride (32 parts) received. It crystallizes from Compared to that in Example 37 in the French Bisbiguanid mentioned in patent specification 933 369, which has the following structural formula a mixture of methanol and ethanol (1: 6) in needles with a melting point from 238 to 24o °. Example 4 21 parts of trimethylene bis-dicyandiamide, 33 parts of p-chloroaniline hydrochloride and Zoo parts of ß-ethoxyethanol are refluxed together at 14o to 15o ° Stirred for 4 hours. The mixture is cooled and washed with 80 parts of dry ether diluted and the solid residue separated and dissolved in hot water. The solution is filtered and the filtrate is allowed to cool. The solid residue consists of i, 3-di- (N "Nl'-p -chlorophenyldiguanide-N., N" ') - propane dihydrochloride and melts at 221 to 222 ° with decomposition.

Example 5 22 parts of tetramethylene bis-dicyandiamide, 33 parts of p-chloroaniline hydrochloride and Zoo parts of ß-ethoxyethanol are refluxed for 3 hours at 14o to 15o ° stirred together. The mixture is then cooled and filtered and the solid residue washed with ethanol and crystallized from hot water. 1,4-Di- (N "Nl'-p -chlorophenyldiguanid-N,;, NS ') - butanedihydrochloride is obtained with a melting point of 253 to 254 °.

Example 6 24 parts of pentamethylene bis-dicyandiamide, 33 parts of p-chloroaniline hydrochloride and zoo parts of ß-ethoxyethanol are refluxed at 14o to 15o ° for 6 hours stirred together. The mixture is then cooled and the solid residue with ethanol washed and crystallized from hot water. i, 5-di- (N1, Ni-p-chlorophenyldiguanid-N5, N5 ') - pentane dihydrochloride comes in colorless needles with a melting point of 25o ° obtain.

Example 7 26 parts of heptamethylene bis-dicyandiamide, 33 parts of p-chloroaniline hydrochloride and 250 parts of ß-ethoxyethanol are refluxed together at 14o to 15o ° Stirred for 90 minutes. The mixture is then cooled and filtered and the solid residue washed with ethanol and recrystallized from hot water. 1, 7-Di- (N1, Nl'-p-chlorophenyldiguanid-N5, N5 ') - heptane dihydrochloride turns into colorless crystals obtained with a melting point of 253 to 254 °.

Example 8 10 parts of hexamethylene bis-dicyandiamide, 13.2 parts of m-chloroaniline hydrochloride and 100 parts of ß-ethoxyethanol are together at 1q.5 ° on the reflux condenser Stirred for 9 hours. The mixture is cooled and the filtrate is diluted with water and filtered. Ammonium chloride is added to the filtrate in 10% strength aqueous solution, which is filtered again, and the solid residue obtained is from 5o% aqueous ethanol crystallized. 1,6-di- (Nl, N, '- m -chlorophenyldiguanide-N "N5) -hexane dihydrochloride is obtained in colorless solid crystals with a melting point of 233-234 °.

Example 9 10 parts of hexamethylene bis-dicyandiamide, 15.1 parts of 2, 5-dichloroaniline hydrochloride and 100 parts of β-ethoxyethanol are stirred together for 8 hours in a reflux condenser. The mixture is cooled and filtered and the solid residue is washed with acetone. It is then crystallized out again from 40% aqueous ethanol. 1,6-Di- (Nl, N1'-2, 5 - dichlorophenyldiguanid - N5, Nj) - hexane dihydrochloride is obtained in cream-colored needles with a melting point of 249 to 25o °.

Example 10 1o parts of hexamethylene bis-dicyandiamide, 15 parts of 3,4-dichloroaniline hydrochloride and 5o parts of ß-ethoxyethanol are refluxed at 14o to 145 ° for 9 hours stirred together. The mixture is cooled and 50 parts of β-ethoxyethanol are added. It is then filtered and the solid residue is washed with ethanol and acetone. i, 6-Di- (N1, N1'-3, 4-dichlorophenyldiguanid-N ", NS ') - hexanedihydrochlo-NC-NH-C (: NH) -NH- [CH2] "- NH-C (: NH) -NH-CN with one or more amines of the formula ANH2 in a molar ratio 1: 2 or b) a polymethylenediamine of the formula N H2 [C112] "- NH2 with a dicyandiamide of the formula A-NH-C (: NH) -NH-CN in a molar ratio of 1: 2, where in the formulas A denotes a phenyl radical formed by an alkyl; Alkoxy, nitro or halogen group rid is obtained in colorless crystals with a melting point of 259 to 26o °.

Example 11 1o parts 1, 4-di-n-propoxybenzene-co, co'-bis-dicyandiamide, 100 parts of p-chloroaniline hydrochloride and 100 parts of ß-ethoxyethanol are used together in 14o to 145 ° heated on the reflux condenser for 9 hours. The solid residue is with acetone washed and crystallized from 5o% ethanol. The colorless ones thus obtained Crystals of co, co'-di- (N1, Nl'-p-chlorophenyldiguanid - Ns, NS ') -1, 4 - di - n-propoxybenzene dihydrochloride have a melting point of 247 to 249 °.

Example 12 10, 2 parts of hexamethylene bis-dicyandiamide, 14.7 parts of m-nitroaniline hydrochloride and 70 parts of 70% saturated aqueous dioxane are mixed and the mixture is stirred for 10 hours and heated on the reflux condenser. It is then cooled and zoo parts of water and 52 parts of saturated brine are added. It is then filtered and the solid residue is washed with water and recrystallized from water. 1,6 - Di - (NI, Nj = m - nitrophenyldiguanid - Ns, N "') -. Hexanedihydrochloride is obtained as a pale yellowish solid crystalline substance with a melting point of 234 to 235 °.

Claims (1)

Claim: Process for the production of bactericidal substances, characterized in that a) a -Polymethylenbisdicya.ndiamid of the formula can be substituted, the two A can be the same or different, n denotes an integer between 3 and 9 inclusive and the polymethylene chain by oxygen atoms and / or aromatic nuclei can be interrupted. Cited publications: French patent specification No. 933 369: German patent specification No. 620 509; U.S. Patent No. 2,510,081.