BIOCIDAL ALCOHOLS, THEIR PRODUCTION AND THEIR USE

Abstract: Biocidal alcohols of general formulae (I) and (II) are described in which R2 is selected from C1-C8 alkyl, uninterrupted or interrupted by oxygen and/or sulphur atoms, C2-C8 alkenyl and C3-C8 alkynyl, R1 is a significance of R2, independently of R2, or in compounds of formula (I) is hydrogen, each of R3 to R7, independently, is a significance of R2, optionally attached to the aromatic ring by -S- or -O-, is H, halogen, nitrile or thiocyanate, and n is 1 or 2.

Description: Biocidal alcohols, their production and their use The invention relates to biocidal alcohols, their production and their use. In particular, the invention relates to a group of antimicrobially, fungicidally and antimycobacterially effec¬ tive alcohols, to a process for their production and to the use of these alcohols in disinfectants, antiseptics, antimycotics, deodorants and preservatives. The antimicrobial action of aliphatic alcohols is sufficiently known. Their disinfecting action increases with increasing chain length and reaches an optimum, say, in the case of 1- octanol. Primary alcohols are generally more effective than the corresponding secondary alcohols, and these in turn surpass the action of the corresponding tertiary alcohols, i.e. the action decreases e.g. in the order n-butanol - sec. butanol - tert. butanol. 2-ethyl hexanol has proved particularly effective. Unfortunate¬ ly, however, this alcohol has an intensive and unpleasant odour which cannot be masked in practice by adding various perfumes. Its use as an active ingredient in disinfectants or preservati¬ ves is therefore severely limited. The alcohols usually used, ethanol, isopropanol and n-propanol usually have to be used in concentrations of more than 50 % by wt. for the disinfection of surfaces. To deactivate viruses which are important as regards hygiene - such as e.g. Hepatitis B - the alcohol contents of hand disinfectants have to be in¬ creased to above 80 % by wt. Disinfectants with high alcohol contents have a series of dis¬ advantages such as for example low flash points, inadequate material compatibility above all with plastics such as e.g. plexiglas, a rapid evaporation from the skin and surface areas to be disinfected and thus no sufficient long term action, such as is e.g. indispensable for surgical hand disinfection, and an incompatibility with mucous membranes and wounds; concentra¬ tions of above 10 % by wt. already lead to an unpleasant bur- ning. From the series of alkyl aryl alcohols, benzyl alcohol, phenet- hyl alcohol and 3-phenyl-l-propanol are known to be antimicro- bially effective. Benzyl alcohol is relatively easily oxidized to benzaldehyde which draws attention to itself in practice by its smell of bitter almonds. Phenethyl alcohol is the main constituent of rose oil and determines the character of the odour particularly when used for preserving cosmetics. Because of their weak action against fungi, both benzyl alcohol and phenethyl alcohol have to be combined with other active ingre¬ dients. 3-phenyl-l-propanol definitely presents itself as an antimicrobial active ingredient because of its pleasant and mild odour; however, its antimicrobial action, is unfortunate¬ ly not sufficient for it to be used by itself as a disinfectant or preservative. Also known is the antimicrobial action of the phenoxyalkanols, e.g. phenoxyethanol or 2-phenoxy-l-propanol. It is also used in practice for preserving cosmetics. The effectiveness - particu- larly against fungi - does however demand a relatively high use concentration. These alcohols have therefore to be combined with other active ingredients, e.g. with cationic compounds and/or aldehydes, particularly for the production of disinfec¬ tants. It is therefore the object of the invention to find especially anti icrobially and fungicidally effective alcohols which, used alone or in combination with the aforementioned alcohols, pro¬ duce disinfectants or preservatives which are characterized by a reduced total alcohol content, an excellent action against microorganisms - preferably against fungi - and an acceptable odour. To achieve this object, the novel compounds (alcohols) of gene¬ ral formulae I and II are proposed according to claim 1: in which R 2 is selected from Cj-Cβ alkyl, uninterrupted or interrupted by oxygen and/or sulphur atoms, C 2 -C 8 alkenyl and C 3 -C 8 alkynyl, R ; is a significance of R 2 , independently of R 2 , or in co - pounds of formula I is hydrogen, each of R 3 to R 7 , independently, is a significance of R 2 , optio¬ nally attached to the aromatic ring by -S- or -0-, is H, halo¬ gen, nitrile or thiocyanate, and n is 1 or 2, with the proviso, that in compounds of formula I i) where R j and all groups R 3 to R 7 are hydrogen, then n = 2; R x and R 2 are Ci-Cs alkyl and all groups R 3 to R 7 are hydrogen, then n = 2; Rj, R 2 and R < , are methyl and all groups R 3 and R 5 to R 7 are hydrogen, then n = 2; Rj and all groups R 3/ R , R 6 and R 7 are hydro¬ gen and R 5 is methyl or methoxy, then n = 2; R lf R 3 , R 6 and R 7 are hydrogen, R 2 is methyl and R 4 and/or R 5 are H or C-C 6 alkyl, then n = 2; vi) where R x and R to R 7 are hydrogen, R 2 is methyl and R 3 is methyl or methoxy, then n = 2; vii) where R R 3 , R 5 and R 7 are hydrogen, R 2 is methyl, R 4 and R 6 are methyl or R 4 is hydrogen and R 6 is methyl, then n = 2; and with the proviso, that in compounds of formula II where Rj is methyl or pentyl and all other groups R 3 to R 7 are hydroge , then n = 2. These alcohols can be produced in accordance with the process according to Claim 10 or 11. Preferred embodiments are the subject-matter of the dependent claims. It has surprisingly been shown that the action of the parent compound of the alcohols according to the invention, i.e. 3- phenyl-1-propanol or 4-phenyl-1-butanol or the corresponding propenols or butenols, in particular against fungi, is significantly increased when substituents are introduced into the 2-position in the case of the propanols, i.e. n = 1, or into the 3-position in the case of the butanols, i.e. n = 2 , and optionally additionally into the aromatic core. In preferred embodiments R 2 is selected from Cj-C 5 alkyl, uninterrupted or inter¬ rupted by oxygen and/or sulphur atoms, C 2 -C 5 alkenyl and C 3 -C 5 alkynyl, Rj is a significance of R 2 , independently of R 2 , or in compounds of formula I is hydrogen, each of R 3 to R 7 , independently, is a significance of R 2 , optionally attached to the aromatic ring by -S- or -0-, is hydrogen, fluorine, chlorine or bromine, and preferably R 2 is methyl ethyl, ethenyl, propyl, propenyl, propargyl, butyl and amyl, Rj is a significance of R 2 , independently of R 2 , or in com- pounds of formula I is hydrogen, each of R 3 to R 7 , independently, is a significance of R 2 is hydrogen, methyl-X-, ethyl-X-, ethenyl-X-, propyl-X-, propenyl-X-, propargyl-X, isopropyl-X, isopropenyl-X-, t- butyl-X-, methoxymethyl-X-, methoxyethyl-X-, ethoxymethyl- X-, ethoxyethyl-X-, methoxypropyl-X- or ethoxypropyl-X-, where X is -0- or -S-. It is preferred that n = 1. Any combinations of groups according to the above definitions are also possible. These alcohols according to the invention are suitable as anti- microbial and fungicidal active ingredients for disinfectants, antiseptics, antimycotics, deodorants and preservatives. The invention covers also a composition which contains at least one of said compounds of formula I or II and a compound selec¬ ted from alcohols, surfactants and solvents. It is preferred that the composition contains a compound of formula I or II in a quantity of 0.01 to 10 % by wt., in particular 0.05 to 8 % by wt. and preferably 0.1 to 5 % by wt. More preferred a composi¬ tion according to the invention contains a) 0.01 to 10 % by wt. of a compound of formula I or II, and b) 0.1 to 90 % by wt. of a compound selected from C^-Ce alkyl alcohols, unsubstituded or substituted with a C 6 -C 12 aryl, aralkyl or aryloxy group, anionic, cationic, amphoteric or nonionic surfactants, dimethylformamide, betaines and gly¬ cerine. Preferred compounds summarized in b) are, for example, ethy- leneglycol ethers such as "Rewopal MPG 40" (which is tetraethy- leneglycol monophenyl ether), ethoxylated higher alkyl alcohols such as "Brij 58" (which is polyoxyethylene-20-cetylalcohol), ethanol, 1-propanol, 2-propanol sulfosuccinate, betaine, phe- noxyethanol and phenethylalcohol. Said alkyl alcohols or mixtures thereof may be present in an amount of 20 to 85 % by wt., specifically 25 to 80 % by w . Said surfactants or mixtures thereof may be present in an amount of 1 to 30 % by wt., specifically 5 to 25 % by wt. The other mentioned compounds may each be present in an amount of 0.1 to 20 % by wt., specifically 0.5 to 20 % by wt, e.g. 1.0, 2.0 or 3.0 and up to 10 or 12 % by wt. The invention also covers the production of said compounds of formula I or II. Described in DE 35 31 585 is the production of such alcohols using Grignard reactions. However, the disadvan¬ tages of Grignard reactions are adequately known. The process according to the invention offers several advan¬ tages over the Grignard processes. It is particularly advanta¬ geous that according to the invention all alcohols of general O 96/19428 - 7 - formula I can be produced according to the same process. This is a malonic ester synthesis with subsequent decarboxylation and reduction. In the case of n = 2, the alcohols of general formula I can be obtained via the compounds of formula II using alkylation instead of hydrogenatio . This uniform and simple process consists of the following reac¬ tion steps: l_0' 3 Alkylation of dialkyl malonate, preferably diethyl malonate with an alkyl halids, preferably a bromide, to give the monosubstituted malonic ester, as a result of which the group R 2 is introduced. Second alkylation with an aryl-substituted benzyl halide, preferably a chloride or bromide, as a result of which the groups R 3 to R 7 are introduced, provided they are not hydro¬ gen. O 96/19428 - 8 - 3. Saponification and subsequent decarboxylation to give the 3-aryl-substituted propionic acid and treatment by distil¬ lation of same. 4. Reduction to " the desired alcohol of formula I, e.g. with lithium aluminium hydride in diethyl ether or tert.-butyl methylether. The alcohols of formula II with n = 1 can for example be obtai- ned via a Perkin condensation reaction of a corresponding aro¬ matic aldehyde with anhydrides with simultaneous decarboxyla¬ tion and subsequent reduction of the acid in question with lithium aluminium hydride. I. UAIH ( TBDME ) The alcohols of formula II with n = 2 are obtained for example from the respective alcohols with n = 1 via a chain elongation. The tosylate of alcohol II (n = 1) is substituted nucleophili- cally by NaCN and saponified. The resulting acid can be reduced with lithium aluminium hydride to the desired alcohol II (n=2). II (it*.1) NaCN (EtOH l ) KOH (EιOH) -_ reflux h reflux id 2) H3O- II(n=2) The alcohols I with n = 2 can be obtained in analogous manner. I (π=I) Kn=2) By reducing alcohols of formula II with a reducing agent such as l i th i um aluminium hydride or alkylation agents such as li ¬ th i um dialkyl cuprate or trialkyl boron, the alcohols of formu- la I can be obtained. General synthesis instructions for alcohols of formula I using malonic acid diethyl ester 1. General instructions for the first alkylation of malonic acid diethyl esters: 200 mmol malonic acid diethyl ester and 200 mmol R 2 -alkyl bromi¬ de (or chloride) are introduced first into a 250 ml triple- necked flask with internal thermometer, reflux condenser and dropping funnel and the whole is cooled to 10 to 15°C. 68.05 g (200 mmol) 20 % NaOEt in EtOH are slowly added dropwise (over 30 minutes) via a dropping funnel so that the temperature does not exceed 20°C. The mixture is then stirred for a further 30 minutes at 20°C and finally heated to 50 to 60°C for 1 hour. After cooling, the mixture is neutralized with glacial acetic acid (optionally cooling; pH monitored until the buffer pH value is reached) . The resulting NaBr is separated off with a frit and then washed with a little cold EtOH. The main quantity of alcohol in the filtrate is distilled off at normal pressure. The filtrate is mixed with 50 ml H 2 0 and 1 ml cone. HC1, and the organic and the aqueous phases are separated from one another. The organic phase is kept for further use (see below) and the aqueous phase is extracted with 2 x 50 ml ether (if phase sepa¬ ration does not take place, the filtered-off NaBr is used to increase the density, as a result of which a phase separation is initiated). The combined organic phases are dried over sodi¬ um sulphate and the solvent is removed in a vacuum. The thus- formed crude product (R 2 -substituted malonic ester) can be further used directly for the subsequent saponification. 2. General instructions for the second alkylation of alkyl malonic acid diethyl esters: 200 mmol R 2 -substituted malonic acid diethyl ester and 200 mmol R 3 -R 7 -substituted benzyl bromide (or chloride) are introduced first into a 250 ml triple-necked flask with internal thermome¬ ter, reflux condenser and dropping funnel and the whole is cooled to 10 to 15.oC.. 68.05 g (200 mmol) of 20 % NaOEt in EtOH are slowly added dropwise (over 30 minutes) via a dropping funnel so that the temperature does not exceed 20°C. The mixtu¬ re is then stirred for a further 30 minutes at 20°C and finally heated to 50 to 60°C for 1 hour. After cooling, the mixture is neutralized with glacial acetic acid (optionally cooling; pH monitored until the buffer pH value is reached) . The resulting NaBr is separated off with a frit and then washed with a little cold EtOH. The main quantity of alcohol in the filtrate is distilled off at normal pressure. The filtrate is mixed with 50 ml H 2 0 and 1 ml cone. HCl, and the organic and the aqueous phases are separated from one another. The organic phase is kept for further use (see below) and the aqueous phase is ex¬ tracted with 2 x 50 ml ether (if phase separation does not take place, the filtered-off NaBr is used to increase the density, as a result of which a phase separation is initiated). The combined organic phases are dried over sodium sulphate and the solvent is removed in a vacuum. The thus-formed crude product (disubstituted malonic ester) can be further used directly for the subsequent saponification. 3. General instructions for the saponification of disubstitu¬ ted malonic esters: 100 mmol of the disubstituted malonic ester are refluxed with a solution of 45 g cone. KOH (45%) and 50 ml EtOH for 3 hours. The main quantity of ethanol is distilled off under weak vacu¬ um, the remaining residue is dissolved in H 2 0 until the water is clear and cone. HCl is added dropwise, accompanied by cooling with ice, until the pH value is 1. The aqueous phase is extrac¬ ted with 100 ml and then 2 x 50 ml ether. The combined organic phases are dried over sodium sulphate, the solvent is removed in a vacuum and the remaining oil is dried over night in a desiccator. The crude product (disubstituted malonic acid) can be further used for the subsequent decarboxylation without further purification; small residual quantities of ethanol or water do not cause disturbance. 4. General instructions for the decarboxylation of disubstituted malonic acids: The disubstituted malonic acid is heated for 3 hours at 180 * C (C0 2 cleavage). Residual quantities of ethanol and H 2 0 and fruit esters are then distilled off at normal pressure (bath temperature 230 to 250'C). After applying a vacuum (20 to 25 mbar) the 2,3-disubstituted propionic acid is subjected to fractional distillation. To remove moisture that has distilled over and not very volatile components, the distillates can be dried in a desiccator. 5. General instructions for reducing disubstituted propionic acids with lithium aluminium hydride: 3.13 g (82.5 mmol) LiAlH 4 are introduced first into 100 ml of abs. ether. 100 mmol 2, 3-disubstituted propionic acid in 50 ml ether are then slowly added dropwise (possibly with cooling), so that the ether boils easily. After the addition is finished, the mixture is stirred for a further 1 h at room temperature and then refluxed for 4 h. The cooled reaction mixture is carefully introduced with stirring into 200 ml iced water and stirred until the evolution of hydrogen is no longer to be observed. The whole is then mixed with 50 ml 10 % H 2 S0 4 , as a result of which the aluminium hydroxide precipitate dissolves. The phases are separated and the aqueous phase is extracted with 3 x 100 ml ether. The combined organic phases are washed with 3 x 50 ml of semi-concentrated NaOH and 2 x 50 ml saturated NaCl solution, dried over sodium sulphate and the solvent is removed in vacuum. The 2, 3-disubstituted propanol is purified by distillation. Synthesis examples Selected as synthesis examples were (±)-2-benzyl butanol (R j =H; R 2 =Et; R 3 =R 4 =R 5 =R 6 =R 7 =H) , (±)-2-(3-methylbenzyl) butanol (R j =H, R 2 =Et; R 3 =H; R 4 =Et; R 5 "R 6 ~R 7 "H ^ and (± )-2-(3-chlorobenzyl) butanol R 2 =Et; R 3 —H; R 4 —Cl; Rg=Rg=R =H) . (±)-2-benzyl butanol: 20 % total yield; colourless liquid with weak, pleasant odour; d = 0.975; n D 20 = 1.5178; IR corresponds to the structure. H-NMR: 0.90 (t; 3H, CH 2 C// 3 ), 1.30 (dq; 2H, C# 2 CH 3 ) , approx . 1.65 ( ; 1H, CH) , 2.30 (s; 1H, OH), 2.60 (d; 2H, AτCH 2 ) , 3.45 (d; 2H, CH 2 0 ) , 7.0-7.4 ("s"; 5H, Artf) . (±)-2— (3-methylbenzyl) butanol: 16 % total yield; colourless liquid with slight lily of the valley-type odour; d = 0.963; n D 20 = 1.5152; IR corresponds to the structure. ! H-N R: 0.90 (t; 3H, CH 2 C// 3 ) , 1.30 (dq; 2H, C// 2 CH 3 ), approx. 1.6 (m; 1H, CH) , 2.25 (s; 3H, AzCH 3 ) , 2.40 (s; 1H, OH), 2.55 (d; 2H, ArCH 2 ) , 3.45 (d; 2H, CH 2 0H) , 6.7-7.2 (m; 4H, ArH) . (±)-2-(3-chlorobenzyl) butanol: 16 % total yield; slightly yellow liquid with discreet, pleasant odour; d = 1.099; n D 20 = 1.5322; IR corresponds to the structure. H-NMR : 0.90 (t; 3H, CH 2 C# 3 ), 1.30 (dq; 2H, C// 2 CH 3 ) , 1.55 (m; 1H, CH) , 2.55 (d; 2H, AτCH 2 ) , 3.30 (s; 1H, OH), 3.45 (d; 2H, Ctf 2 OH), 6.9-7.2 ("s"; 4H, Artf) . Formulae of the alcohols treated below: OC -cιX Applications MIC (minimum inhibiting concentration) values a) MIC values, water—soluble Standard formulation: Rewopal MPG 40 25.0 g aromatic alcohol 10 mmol de .* water to 100 g lactic acid for adjusting the pH value to 7.0 q.s. (*dem. = demineralized) Test germs Staphylococcus aureus ATCC 6538 Proteus vulgaris NCTC 4635 Candida albicans ATCC 10231 Penicillium funiculosum ATCC 36839 Aspergillus niger ATCC 6275 Test method: In sterile test tubes, 5 ml each of the dilutions of the dis¬ infectant in WSH (water of standardized hardness) are mixed with 5 ml double-concentrated casein peptone soybean flour peptone solution (CSL) or CSL and deactivating substances. To determine the bacteriostatic action on Staphylococcus aureus and Proteus mirabilis the tubes are inoculated by adding 0.1 ml of a CSL culture diluted 1:10 with CSL and incubated for 24 h at 37°C. To test the fungistatic action, 0.1 ml of an undiluted CSL culture of Candida albicans which has been incubated at 37°C for 72 h is used in each case. Evaluation takes place after 72 h at 37°C. The highest dilution of the preparation in CSL or CSL and deac¬ tivating substances that still suppresses growth of the test germs after 12 h incubation serves as the measure of the multi¬ plication-inhibiting action (inhibition titre). In the case of the disinhibition tests, the culture media are to be adjusted to a pH value of 7.0 ± 0.2 according to the state of the disinfectant. Data in μmol/100 ml test solution Standard formulation: aromatic alcohol 5.0 % Brij 58 5.0 % 1 ,3-butanediol to 100 Test germs: see above Test method: see above Data in μmol/100 ml test solution Compared with the parent compound 3-phenyl propanol (alcohol Compd. No. , . , , ,. , 1), the alcohols 2-8 according to the invention clearly display microbistatic activities, particularly alcohols 2 , 6 and 8, in almost ten times lower a use concentration. b) MIC values, water-insoluble Solutions of the aromatic alcohols in acetone (w/w) Test germs: Staphylococcus aureus ATCC 6538 Escherichia coli ATCC 11229 Candida albicans ATCC 10231 Aspergillus niger ATCC 6275 Test method: as under 1.; the dilution solutions were prepared in acetone. The size of the covered areas of the plates is given in %; 100% means no inhibiting action. Alcohols 11 and 13 display a very good broad activity spectrum. In contrast, alcohols 10, 14 and 18 display a very good selec¬ tive action, in particular against fungi and yeasts. 2. Antimicrobial effectiveness in the plate diffusion test Standard formulation: aromatic alcohol 1 part dimethylformamide 6 parts Test germs; Staphylococcus aureus ATCC 6538 Pseudomonas aeruginosa ATCC 15442 Proteus mirabilis ATCC 14153 Escherichia coli ATCC 11229 Candida albicans ATCC 10231 Test method: Agar diffusion test The diameters of the inhibition zones are given in mm. Alcohols 12, 15 and 16 show a very strong inhibition of the tested germs, alcohols 13, 14 and 17 showing a strong inhibi- tion 3. Use in an alcoholic surface disinfectant Standard formulation: ethanol (MEK denatured) 25.0 % 1-propanol 35.0 % perfume 0.02 % benzotriazole 0.001 % Marlipal 013/70 0.1% (isotridecanpolyethyleneglycol-(7)-ether C 13 oxo alcohol + 7 mol ethylene oxide) active ingredient additive x% dem. water to 100 Test germ: Ps. aeruginosa Test method: Quantitative surface test according to DGHM (Deutsche Gesell- schaft fur Hygiene and Microbiology = German Association for Hygiene and Microbiology) . In order to exclude the effective¬ ness of the readily volatile alcohol components (ethanol, 1- propanol), the preparations were deposited onto the surfaces and the germs were deposited after approx. 20 minutes. Test surfaces: PVC and OP tiles Data as reduction factors (log stages) Only the preparation with an aromatic alcohol o t e ormu a I according to the invention, 2,2-dimethyl-3-phenyl-1-propanol (2) has an effectiveness against Pseudomonas aeruginosa on PVC and tiles that increases with increasing action time. The other preparations are disinfectant solutions. Use in a foot spray with deodorizing action and simultane¬ ous prevention of athlete's foot Formula: 2-propanol 40.0% aromatic alcohol 0.2 % allantoin 0.5 % dem. water to 100 Test germs: special skin fungi such as Trichophyton rubrum, Trichophyton mentagrophytes (ATCC 9533), Micro¬ sporon gypseum Test method: Determination of the minimum inhibition concen¬ tration (method see under 1.) Data in % Test germs: special skin fungi such as Trichophyton rubrum, Trichophyton mentagrophytes, Microsporon gypseum Test method: Agar diffusion test Data as millimetres inhibition zone With typical fungi which are relevant as regards skin, the formulations with alcohols 6 and 8 according to the invention show a very good action both in the MIC test and in the agar diffusion test. The aforementioned formulations are thus suit¬ able for use in deodorants and products for the prevention of athlete's foot. The parent compound 3-phenyl propanol shows almost similar values as the blank value, i.e. is ineffective. 5. Preservative Standard formulation: sulfosuccinate 12.0% betaine 3.0% aromatic alcohol 0.5% re-fatting agent skin care additives thickener dem. water to 100 Test germs: Germ mixture of Staphylococcus aureus, Staphylococcus epidermis, Escherichia coli, Klebsiella pneu oniae, Enterobacter gergoviae, Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Aspergillus niger, Penicillium funiculosum, Candida albicans ; Total germ count 10 8 -10 9 /ml . Test method: weekly loading of the sample with germ suspen¬ sion; smear onto CS and Sabouraud agar. See also K.-H. Diehl, P. Oltmanns, J. Ramsbotham, Seife, ϋle, Fette, Wachse 118 (1992) 546. Data expressed semi-qualitatively: no growth + slight growth ++ moderate growth +++ heavy growth Preservation with 0.5 % 2,2-dimethyl-3-phenyl propanol (2) is just as effective as that with the known preservative phenoxy¬ ethanol, but displays a more sure (more quickly acting) preser¬ vation in the first two weeks compared with the parent compound 3-phenyl propanol. The alcohols according to the invention are thus suitable as a preserving additive in shampoos and shower gels. 6. Mucous membrane antiseptic Standard formulation: - Cocamidopropyl betaine (30%) 3.0 % glycerin DAB 10 (85%) 0.5% phenoxyethanol 1.0% arom. alcohol 0.5% dem. water to 100 - NaOH to adjust the pH value to 5.5 q.s. Test germs: Pseudomonas aeruginosa ATCC 15442 Staphylococcus aureus ATCC 6538 Test method: Quantitative suspension test according to DGHM Data as reduction factors (log stages) ; C = control The alcohols according to the invention significantly increase the effectiveness against the aforementioned germs, in particu¬ lar against yeasts. 7. Skin antiseptic a) standard formulation: 1-propanol 30.0% 2-propanol 45.0% aromatic alcohol 1.0% dem. water to 100 Test germ: Microsporon luteus ATCC 15442 Test method: Apply 0.2 ml preparation to 10cm 2 skin, allow to dry, cover with TEGADERM* film and leave to work for 1 h, contaminate with 0.1 ml- germ suspension, remove after 15 minutes with ring method Reference: Control against Neo-Kodan" Number of subjects: 10 subjects Data as average value of the reduction factors (RF in log sta¬ ges) of all 10 subjects The formulation with 1.0% α-amyl cinnamyl alcohol (8) also shows the same values in the suspension test according to DGHM as the skin antiseptic Neo-Kadan* used for reference of 50%, 30 seconds, and likewise shows an equal action against the resi¬ dent skin flora (100%, 15 seconds). Moreover, the aforementioned results show that an action against the transient flora is only guaranteed when the α-amyl cinnamyl alcohol (8) substituted according to formula II is used and not the parent compound 3-phenyl propanol (1). b) Standard formulation: 1-propanol 15.0% 2-propanol 30.0% aromatic alcohol 1.0% dem. water to 100 Test germs: Staphylococcus aureus ATCC 6538 Pseudomonas aeruginosa ATCC 15442 Candida albicans ATCC 10231 Test method: Quantitative suspension test according to DGHM Data as reduction factors (log stages) In the aforementioned propanol-reduced formulation, the addi¬ tional action of the α-amyl cinnamyl alcohol is seen in parti¬ cular in the case of Candida albicans. 8. Use in an alcoholic disinfectant for surgical hand disinfec¬ tion Formulation: ethanol 80.0% phenethyl alcohol 2.0% 2,2-dimethyl-3-(3-methylphenyl) propanol (3) 0.4% re-fatting agent humectant dem. water to 100 The requirements of the DGHM guideline for surgical hand dis¬ infection are satisfied by the aforementioned formula both in their immediate action and also in their long-term action. A formulation which contains neither phenethyl alcohol nor 2,2- dimethyl-3-(3-methylphenyl) propanol (3) does not satisfy these requirements. 9. Effectiveness against M. terrae S in the germ carrier expe- riment with standard cotton Standard formulation: Rewopal MPG 40 25.0% - aromatic alcohol 2.0 % dem. water to 100 Test germ: Mycobacterium terrae ATCC 15755 Test method: Production of the germ carriers: To prepare the germ carriers, standard cotton fabric is used which has been thoroughly rinsed in double-di¬ stilled water. The fabric is cut into pieces measuring approximately 1 cm , sterilized in a autoclave and dried. Production of the bacterial suspension: The bacteria are elutriated with 5 ml CSL from a 24 h-old (37°C) culture onto CSA plates measuring approx. 9 cm in diame¬ ter, the suspension being diluted with CSL if necessary. The number of CFU/ml is to be determined using surface culture. It should be > loVml. Procedure for the germ carrier test: The sterilized and dried germ carriers are introduced into the bacterial suspension and left in it for 15 minutes, during which they are turned over twice. A number (4) of contaminated, thoroughly impregnated germ car¬ riers, corresponding to the proposed removal times - 15, 30, 60 and 120 minutes - is placed in a small dish and 10 ml of the disinfectant solution to be tested in WSH are poured over them. Air bubbles are to be removed by repeated turning of the germ carriers. After the corresponding action times, the germ carriers are to be removed from the disinfectant solution, and after rinsing twice in each case for 1 min in 10 ml ML solution (see Appen¬ dix) to which the deactivating substances were optionally ad¬ ded, the germ carriers are placed onto the surface of a Lδwen- stein-Jensen nutrient medium with tweezers and moved backwards and forwards 3 to 4 times using light pressure. After inocula¬ ting the nutrient medium surface the small cloth is to remain lying directly above the condensed water level of the nutrient medium. Germ carriers pre-treated in the same way, but kept in WSH for 120 minutes instead of in disinfectant solution are to be ino¬ culated as a control. The inoculated tubes are incubated at 37°C for 3 weeks. Data expressed qualitatively: E individual colonies τ+ moderate growth M several colonies +++ heavy growth + weak growth ++++ very heavy growth oo lawn growth The alcohols according to the invention, particularly 2, 3 and 8, show a very good action against mycobacteria with relatively long action times and are therefore suitable for use in instru¬ ment disinfectants. The parent compound 1 shows a very much weaker action.

Claims: Patent claims 1. A compound of formula I or II, R 2 is selected from Cj-Cg alkyl, uninterrupted or inter¬ rupted by oxygen and/or sulphur atoms, C 2 -C 8 alkenyl and C 3 -C 8 alkynyl, Rj is a significance of R 2 , independently of R 2 , or in compounds of formula I is hydrogen, each of R 3 to R 7 , independently, is a significance of R 2 , optionally attached to the aromatic ring by -S- or -0-, is H, halogen, nitrile or thiocyanate, and n is 1 or 2, with the proviso, that in compounds of formula I i) where R : and all groups R 3 to R 7 are hydrogen, then n = 2; ii) where R x and R 2 are Cj-Cj alkyl and all groups R 3 to R 7 are hydrogen, then n =2; iii) where R lf R 2 and R_, are methyl and all groups R 3 and R 5 to R 7 are hydrogen, then n =2; iv) where R x and all groups R 3 , R 4 , R 6 and R 7 are hydro¬ gen and R 5 is methyl or methoxy, then n = 2; v) where R i r R 3 , R 6 and R 7 are hydrogen, R 2 is methyl and R 4 and/or R 5 are H or Cx-Cβ alkyl, then n = 2; vi) where R x and Rt, to R 7 are hydrogen, R 2 is methyl and R 3 is methyl or methoxy, then n = 2; vii) where R l R 3 , R 5 and R 7 are hydrogen, R 2 is methyl, R 4 and R 6 are methyl or R 4 is hydrogen and R 6 is methyl, then n = 2; and with the proviso, that in compounds of formula II where R x is methyl or pentyl and all other groups R 3 to R 7 are hydrogen, then n = 2. A compound according to claim 1, in which in which R 2 is selected from C x -C 5 alkyl, uninterrupted or inter¬ rupted by oxygen and/or sulphur atoms, C 2 -C 5 alkenyl and C 3 -C 5 alkynyl, Ri is a significance of R 2 , independently of R 2/ or in compounds of formula I is hydrogen, each of R 3 to R 7 , independently, is a significance of R 2 , optionally attached to the aromatic ring by -S- or -0-, is hydrogen, fluorine, chlorine or bromine. A compound according to claim 1 or 2 in which R 2 is methyl ethyl, ethenyl, propyl, propenyl, propargyl, butyl and amyl, R ! is a significance of R 2 , independently of R 2 , or in com¬ pounds of formula I is hydrogen, each of R 3 to R 7 , independently, is a significance of R 2 , is hydrogen, methyl-X-, ethyl-X-, ethenyl-X-, propyl-X-, propenyl-X-, propargyl-X, isopropyl-X, isopropenyl-X-, t- butyl-X-, methoxymethyl-X-, methoxyethyl-X-, ethoxymethyl- X-, ethoxyethyl-X-, methoxypropyl-X- or ethoxypropyl-X-, where X is -0- or -S-. 4. A compound according to any of the preceding claims in which n = 1. 5. A compound according to one of claims 1 to 4 which is (±)- 2-benzyl butanol, (±)-2-(3-methylbenzyl) butanol or (±)-2- (3-chlorobenzyl) butanol. 6. Composition which contains at least one compound of formula I or II according to one of claims 1 to 5 and a compound selected from alcohols, surfactants and solvents. 7. Composition according to Claim 6 which contains a compound of formula I or II in a quantity of 0.01 to 10 % by wt., in particular 0.05 to 8 % by wt. and preferably 0.1 to 5 % by wt. 8. Composition according to claim 6 or 7 which contains a) 0.01 to 10 % by wt. of a compound of formula I or II, and b) 0.1 to 90 % by wt. of a compound selected from Cj-Cg alkyl alcohols, unsubstituded or substituted with a C 6 -C 12 aryl, aralkyl or aryloxy group, anionic, catio- nic, amphoteric or nonionic surfactants, dimethylform- a ide, betaines and glycerine. 9. Composition according to any of claims 6 to 8 which is a disinfectant, antiseptic, antimycotic, deodorant or preser¬ vative. 10. Process for the production of a compound of formula I in which R 2 is selected from C^Cg alkyl, uninterrupted or inter¬ rupted by oxygen and/or sulphur atoms, C 2 -C 8 alkenyl and C 3 -C 8 alkynyl, Rj is a significance of R 2 , independently of R 2 , or is hydrogen, each of R 3 to R 7 , independently, is a significance of R 2 , optionally attached to the aromatic ring by -S- or -0-, is H, halogen, nitrile or thiocyanate, and n is 1 or 2, wherein a) a malonic acid dialkyl ester is monoalkylated, as a result of which the group R 2 is introduced, b) the monoalkylated malonic acid alkyl ester is dialkylated with a benzyl halide optionally substituted at the aromatic ring, as a result of which the groups R 3 to R 7 are introdu- ced, provided they are not hydrogen, c) the dialkylated malonic acid dialkyl ester is saponified and decarboxylated, as a result of which the corresponding- ly 3-aryl-substituted propionic acid results and d) this 3-aryl-substituted propionic acid is reduced with the formation of the desired alcohol of formula I. 11. Process for the production of a compound of formula II in which R x is selected from alkyl, uninterrupted or inter¬ rupted by oxygen and/or sulphur atoms, C 2 -C 8 alkenyl and C 3 -C 8 alkynyl, each of R 3 to R 7 , independently, is a significance of R l r optionally attached to the aromatic ring by -S- or -0-, is H, halogen, nitrile or thiocyanate, and n is 1 or 2, wherein in the case of n = 1 a corresponding aromatic alde¬ hyde is condensed with an anhydride with simultaneous de¬ carboxylation and then the resulting acid is reduced with lithium aluminium hydride, or in the case of n = 2 the tosylate of the respective alcohol with n = 1 is substitu- ted nucleophilically by NaCN and is saponified and the resulting acid is reduced with lithium aluminium hydride to give the desired alcohol. 12. Use of a compound of formula I or II in which R 2 is selected from ι- B alkyl, uninterrupted or inter¬ rupted by oxygen and/or sulphur atoms, C 2 -C 8 alkenyl and C 3 -C 8 alkynyl, Rj, is a significance of R 2 , independently of R 2 , or in compounds of formula I is hydrogen, each of R 3 to R 7 , independently, is a significance of R 2 , optionally attached to the aromatic ring by -S- or -0-, is H, halogen, nitrile or thiocyanate, and n is 1 or 2, as biocidal active ingredients,

Inventors: BEHRENDS SABINE, BEILFUSS WOLFGANG, BERSCHEID RALF, EGGENSPERGER HEINZ, PUCHSTEIN BURGHARD, BEHRENDS, SABINE, BEILFUSS, WOLFGANG, BERSCHEID, RALF, EGGENSPERGER, HEINZ, PUCHSTEIN, BURGHARD
Applicants: BEHRENDS SABINE, BEILFUSS WOLFGANG, BERSCHEID RALF, EGGENSPERGER HEINZ, PUCHSTEIN BURGHARD, SCHUELKE & MAYR GMBH, BEHRENDS, SABINE, BEILFUSS, WOLFGANG, BERSCHEID, RALF, EGGENSPERGER, HEINZ, PUCHSTEIN, BURGHARD
Application year: 1995
Main classification: C07C33
IPC codes: A01N31, A61K8, A61K31, A61K45, A61L2, A61Q15, A61Q17, C07C29, C07C33, C07C43, C11D3