WO2003078367A2 - Benzyl alcohol derivatives and their use as antimicrobial agents - Google Patents

Benzyl alcohol derivatives and their use as antimicrobial agents Download PDF

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Publication number
WO2003078367A2
WO2003078367A2 PCT/EP2003/002618 EP0302618W WO03078367A2 WO 2003078367 A2 WO2003078367 A2 WO 2003078367A2 EP 0302618 W EP0302618 W EP 0302618W WO 03078367 A2 WO03078367 A2 WO 03078367A2
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alkyl
phenyl
formula
hal
compound
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PCT/EP2003/002618
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French (fr)
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WO2003078367A3 (en
Inventor
Werner Hölzl
Jürgen Koppold
Sophie Marquais-Bienewald
Andrea Preuss
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Ciba Specialty Chemicals Holding Inc.
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Priority to US10/507,965 priority Critical patent/US20050124579A1/en
Priority to JP2003576376A priority patent/JP2005520829A/en
Priority to AU2003208707A priority patent/AU2003208707A1/en
Priority to EP03706613A priority patent/EP1485339A2/en
Publication of WO2003078367A2 publication Critical patent/WO2003078367A2/en
Publication of WO2003078367A3 publication Critical patent/WO2003078367A3/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/08—Oxygen or sulfur directly attached to an aromatic ring system
    • A01N31/14—Ethers
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N31/00—Biocides, pest repellants or attractants, or plant growth regulators containing organic oxygen or sulfur compounds
    • A01N31/08—Oxygen or sulfur directly attached to an aromatic ring system
    • A01N31/16—Oxygen or sulfur directly attached to an aromatic ring system with two or more oxygen or sulfur atoms directly attached to the same aromatic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N55/00—Biocides, pest repellants or attractants, or plant growth regulators, containing organic compounds containing elements other than carbon, hydrogen, halogen, oxygen, nitrogen and sulfur
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/02—Local antiseptics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q15/00—Anti-perspirants or body deodorants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q5/00—Preparations for care of the hair
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
    • C07C43/23—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/235—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring and to a carbon atom of a ring other than a six-membered aromatic ring
    • C07C43/253—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring and to a carbon atom of a ring other than a six-membered aromatic ring containing hydroxy or O-metal groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
    • C07F7/02—Silicon compounds
    • C07F7/08—Compounds having one or more C—Si linkages
    • C07F7/0803—Compounds with Si-C or Si-Si linkages
    • C07F7/081—Compounds with Si-C or Si-Si linkages comprising at least one atom selected from the elements N, O, halogen, S, Se or Te
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

Definitions

  • the present invention relates to the use of benzyl alcohol derivatives for the antimicrobial treatment of surfaces, as antimicrobial active substance against Gram-positive and Gram- negative bacteria, and preservation of cosmetics, household products, textiles, plastics and disinfectants, and also to novel benzyl alcohol derivatives.
  • the benzyl alcohol derivatives used according to the invention have the formula
  • R L R J . and R 3 independently of one another, are unsubstituted C C 20 alkyl, C 5 . 8 cycloalkyl, C 3 -C 20 alkenyl or C C2oalkyl, C 5 - 8 cycloalkyl, C 3 -C 20 alkenyl substituted by d-C 4 alkyl, d -C 4 alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-C C 2 alkyl, amino, -NHC r C 2 oalkyl or -N(C 1 -C 2 oalkyl) 2 ; C 2 -C 20 alkyl which is interrupted by one or more heteroatoms and/or may be substituted; C 2 -C 20 perfluoroalkyl; -(C ⁇ C ⁇ alkyleneJ-Si- ⁇ ris-d- ⁇ alkyl); -(C 2 -C 12 alkylene)-S
  • A is unsubstituted phenyl, naphthyl or C 4 -C 8 cycloalkyl or phenyl, naphthyl or C - C 8 cycloalkyl substituted by d-C 4 alkyl, d-C 4 alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-C ⁇ -C 2 alkyl, amino, -NHd-C 20 alkyl or -N(d-C 2 oalkyl) 2 ; or -CH 2 CH 2 (CH 2 CH 2 O) 0 -B;
  • B is unsubstituted C C 4 alkyl or phenyl or C C alkyl or phenyl substituted by d-C alkyl, d-C 4 alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-C C 2 alkyl, amino, -NHC C 20 alkyl or -N(C C 20 alkyl) 2 ; o is an integer from 0 - 10; n and m, independently of one another, are 0 or 1 ; and x, y and z, independently of one another, are 0 to 12; and mixtures thereof and salts thereof, where compounds of the formula (1) in which
  • Ri and R 2 or R ⁇ and R 3 or R 2 and R 3 are methyl or ethyl are not included.
  • the C 2 -C 20 alkyls interrupted by one or more heteroatoms are interrupted, in particular, by O, S or N.
  • d-C 20 Alkyls are straight-chain or branched alkyl radicals, such as, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, de- cyl, undecyl, dodecyl, tetradecyl, pentadecyl or hexadecyl.
  • C C 4 Alkoxy is, for example, methoxy, ethoxy, n-propoxy, isopropoxy or n-butoxy.
  • Halogen is fluorine, chlorine, bromine or iodine.
  • Ri, R 2 and R 3 independently of one another, are unsubstituted C 5 -C ⁇ 6 alkyl, C 3 -C 6 cycloalkyl or C 3 -C ⁇ 6 alkenyl or C 5 -C 16 alkyl, C 3 -C 6 cycloalkyl or C 3 -C 16 alkenyl substituted by d- C 4 alkyl, d-C 4 alkoxy, hydroxy, phenyl, halogen, CN, COOH, COO-d-C 2 -alkyl, amino, NHCrC 2 oalkyl, N(C 1 -C 20 alkyl) 2 ; C 3 -C ⁇ 6 alkyl which is interrupted by one or more heteroatoms from the group O, N or S; Crd ⁇ perfluoroalkyl; -(d-C 12 alkylene)-Si-(tris-d- 12 alkyl); -(C 1 -C 6 alkylene)-Si-(d-
  • A is unsubstituted phenyl or C 5 -C 6 cycloalkyl or phenyl or C 5 -C 6 cycloalkyl substituted by C ⁇ C ⁇ Ikyl, d-C 4 alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-C r C 2 alkyl, amino, NHC ⁇ -C 20 alkyl or N(CrC 20 alkyl) 2 ;
  • B is unsubstituted C ⁇ -C 2 alkyl or phenyl or CrC 2 alkyl or phenyl substituted by d-C 4 alkyl, C ⁇ C ⁇ Ikoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-d-C 2 alkyl, amino, NHC C 20 alkyl or N(d-C 2 oalkyl) 2 ; x, y and z, independently of one another, are an integer from 0 to 4; o is an integer from 0 to 5; and n and m, independently of one another, are 0 or 1.
  • R t is -CH 2 SiC 6 H 5 ; -(CH 2 ) 5 CH 3 ; -(CH 2 ) 7 CH 3 ; -CH(CH 2 CH 3 ) 2 ; or -CH(CH 3 )(CH 2 ) 4 CH 3 .
  • Further interesting compounds which can be used according to the invention have the formulae
  • Pref erred are the compounds of formulae (14), (28), (37), (38), (39) and (40).
  • Benzyl alcohol derivatives used according to the invention are prepared by known methods,
  • the synthesis of the compounds of the formula (2b) is, in particular, carried out in a solvent, such as dimethylformamide, methanol, ethanol, acetone, acetonitrile or ethyl acetate, to which an (auxiliary) base, such as, for example, sodium hydride, sodium alkoxides or alkali metal carbonate, has been added, at a temperature of from 40 to 120°C, preferably 60 to 100°C.
  • a solvent such as dimethylformamide, methanol, ethanol, acetone, acetonitrile or ethyl acetate
  • an (auxiliary) base such as, for example, sodium hydride, sodium alkoxides or alkali metal carbonate
  • Preferred halides are chlorides and bromides.
  • the reaction time is 2 to 48 hours. A preferred reaction time is about 18 hours.
  • the reducing agents used are customary reducing agents, such as, for example, hydrogen, metal hydrides or dithionite.
  • the solvents used are, for example, diethyl ether or tetrahydrofuran.
  • the reducing agent is customarily added in a 10- to 20-fold excess.
  • the reaction temperature is usually between 20 and 50°C, preferably 25 to 45°C.
  • the benzyl alcohols used according to the invention exhibit a marked antimicrobial effect, in particular against pathogenic Gram-positive and Gram-negative bacteria and also against skin flora bacteria. They are therefore suitable, in particular, for the disinfection, deodoriza- tion, and also the general and antimicrobial treatment of the skin and mucosae, and skin appendages (hair), very particularly for hand and wound disinfection. They are therefore suitable as antimicrobial active substances and preservatives in bodycare compositions, such as, for example, shampoos, bath products, haircare compositions, liquid and solid soaps (based on synthetic surfactants and salts of saturated and/or unsaturated fatty acids), lotions and creams, deodorants, other aqueous or alcoholic solutions, e.g. cleansing solutions for the skin, moist cleansing wipes, oils or powders.
  • bodycare compositions such as, for example, shampoos, bath products, haircare compositions, liquid and solid soaps (based on synthetic surfactants and salts of saturated and/or unsatur
  • the invention therefore further provides a bodycare composition comprising at least one compound of the formula (1) and cosmetically acceptable carriers or auxiliaries.
  • the bodycare composition according to the invention comprises 0.01 to 15% by weight, preferably 0.1 to 10% by weight, based on the total weight of the composition, of the benzyl alcohol compound of the formula (I) and cosmetically acceptable auxiliaries.
  • the bodycare composition Depending on the form in which the bodycare composition is present, as well as the benzyl alcohol compound of the formula (1), it also has further constituents, such as, for example, sequestering agents, dyes, perfume oils, thickening or setting agents (consistency regulators), emollients, UV-absorbers, skin protectants, antioxidants, additives which improve the mechanical properties, such as dicarboxylic acids and/or Al, Zn, Ca, Mg salts of C ⁇ -C ⁇ fatty acids and optionally preservatives.
  • constituents such as, for example, sequestering agents, dyes, perfume oils, thickening or setting agents (consistency regulators), emollients, UV-absorbers, skin protectants, antioxidants, additives which improve the mechanical properties, such as dicarboxylic acids and/or Al, Zn, Ca, Mg salts of C ⁇ -C ⁇ fatty acids and optionally preservatives.
  • the bodycare composition according to the invention can be formulated as a water-in-oil emulsion or oil-in-water emulsion, as an alcoholic or alcohol-containing formulation, as a vesicular dispersion of an ionic or nonionic amphiphilic lipid, as a gel, solid stick or as an aerosol formulation.
  • the cosmetically acceptable auxiliary preferably comprises 5 to 50% of an oil phase, 5 to 20% of an emulsifier and 30 to 90% of water.
  • the oil phase can comprise any oil suitable for cosmetic formulations, such as, for example, one or more hydrocarbon oils, a wax, a natural oil, a silicone oil, a fatty acid ester or a fatty alcohol.
  • Preferred mono- or polyols are ethanol, isopropanol, propylene glycol, hexylene glycol, glycerol and sorbitol.
  • Cosmetic formulations according to the invention are used in various fields.
  • the following compositions are considered: skincare compositions, such as, for example, skin washing and cleansing compositions in the form of bar or liquid soaps, syndets or washing pastes, bath preparations, such as, for example, liquid bath preparations (foam baths, milks, shower preparations) or solid bath preparations, such as, for example, bath tablets and bath salts; skincare compositions, such as, for example, skin emulsions, multiple emulsions or skin oils; decorative bodycare compositions, such as, for example, make-up for the face in the form of day or powder creams, face powder (loose and pressed), blusher or cream make-up, eyecare compositions, such as, for example, eyeshadow preparations, mascara, eyeliner, eye creams or eye-fix creams; lipcare compositions, such as, for example, lipstick, lip gloss, lip liner pencil, nailcare compositions, such as nail varnish, nail varnish remover, nail hardeners, or
  • An antimicrobial soap has, for example, the following composition: 0.01 to 5% by weight of the compound of the formula (1) 0.3 to 1 % by weight of titanium dioxide, 1 to 10% by weight of stearic stearic acid ad 100% of soap base, such as, for example, the sodium salts of tallow fatty acid and coconut fatty acid or glycerol.
  • a shampoo has, for example, the following composition: 0.01 to 5% by weight of the compound of the formula (1), 12.0% by weight of sodium laureth-2 sulphate,
  • a deodorant has, for example, the following composition:
  • the invention further provides an oral composition comprising 0.01 to 15% by weight, based on the total weight of the composition, of the compound of the formula (1) and orally acceptable auxiliaries.
  • Example of an oral composition 10% by weight of sorbitol, 10% by weight of glycerol,
  • the oral composition according to the invention can be, for example, in the form of a gel, a paste, a cream or an aqueous preparation (mouthwash).
  • the oral composition according to the invention can comprise compounds which release fluoride ions, which are effective against the formation of caries, e.g. inorganic fluoride salts, such as, for example, sodium fluoride, potassium fluoride, ammonium fluoride or calcium fluoride, or organic fluoride salts, such as, for example, amine fluorides, which are known under the trade name Olafluor.
  • inorganic fluoride salts such as, for example, sodium fluoride, potassium fluoride, ammonium fluoride or calcium fluoride
  • organic fluoride salts such as, for example, amine fluorides, which are known under the trade name Olafluor.
  • the benzyl alcohol derivatives of the formula (1) used according to the invention are suitable for the treatment, in particular preservation, of textile fibre materials.
  • the fibre materials are undyed and dyed or printed and are made of, for example, silk, wool, polyam- ide or polyurethanes, and in particular cellulosic fibre materials of all types.
  • Such fibre materials are, for example, natural cellulose fibres, such as cotton, linen, jute and hemp, and also regenerated cellulose.
  • Preferred suitable textile fibre materials are made of cotton.
  • the benzyl alcohols according to the invention are also suitable for the treatment, in particular for the antimicrobial finishing or preservation, of plastics, such as, for example, polyethylene, polypropylene, polyurethane, polyester, polyamide, polycarbonate, latex etc..
  • plastics such as, for example, polyethylene, polypropylene, polyurethane, polyester, polyamide, polycarbonate, latex etc.
  • Fields of use for these are, for example, floor coverings, plastic coatings, plastic container and packaging materials; kitchen and bathroom utensils (e.g. brushes, shower curtains; sponges, bathroom mats), latex, filter materials (air and water filters), plastic articles used in the medical sector, such as, for example, bandaging materials, syringes, catheters etc., so-called medical devices, gloves and mattresses.
  • Paper too, such as, for example, hygiene papers, can be antimicrobially finished with the benzyl alcohols according to the invention.
  • nonwovens such as, for example, nappies, sanitary towels, panty liners, wipes for the hygiene and household sector, can be antimicrobially finished according to the invention.
  • benzyl alcohols of the formula (1) are used in washing and cleaning formulations, such as, for example, in liquid and powder detergents or fabric softeners.
  • the benzyl alcohols can be used, in particular, also in household and all-purpose cleaners for the cleaning and disinfection of hard surfaces.
  • a cleaner has, for example, the following composition:
  • the preservation and antimicrobial finishing of technical products and also use as biocide in technical processes is also possible, such as, for example, in the treatment of paper, in particular in paper- treatment liquors, printing thickeners made of starch or cellulose modifications, surface coatings and paints.
  • the benzyl alcohols of the formula (1) are also suitable for the antimicrobial treatment of wood and also for the antimicrobial treatment, preservation and finishing of leather.
  • the compounds according to the invention are suitable for protecting cosmetic products and household products against microbial decay.
  • the benzyl alcohols which can be used according to the invention are known compounds or novel compounds.
  • R' ⁇ ,R' 2 and R' 3 independently of one another, are unsubstituted d-C 20 alkyl, C 5 . 8 cycloalkyl, C 3 -C 20 alkenyl or CrC 20 alkyl, C 5 .
  • A is unsubstituted phenyl, naphthyl or C 4 -C 8 cycloalkyl or phenyl, naphthyl or C 4 -
  • B is unsubstituted d-C 4 alkyl or phenyl or C C 4 alkyl or phenyl substituted by d-C 4 alkyl, d-C 4 alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-d-C 2 alkyl, amino, -NHC r C 20 alkyl or -N(d-C 20 alkyl) 2 ; o is an integer from 0 - 10; n and m, independently of one another, are 0 or 1 ; and x, y and z, independently of one another are 0 to 12; with the proviso that if n and m are 0, is not an alkyl group, if R' t is methyl or ethyl and either n or m is 1 , then R' 2 or R' 3 is not a methyl or benzyl group, and if R'i is a linear C 12 alkyl group and
  • Example 1 The examples below, which do not limit the invention, are used for illustration.
  • Example 1 The examples below, which do not limit the invention, are used for illustration.
  • Example 1 Example 1 :
  • the purity is 97 area % LC(254nm).
  • the other compounds in Table 1 can be prepared analogously to Synthesis Example 1 using the respective starting materials. Determination of the minimum inhibition concentration (MIC value) in microtitre plates
  • Casein-soy flour-peptone broth for the preparation of the precultures of the test bacteria and yeast.
  • test substances are predissolved in dimethyl sulphoxide (DMSO) and tested in a dilution series of 1 :2.
  • DMSO dimethyl sulphoxide
  • the bacteria are cultivated overnight in CASO broth and sponged off with 10 ml of 0.85% sodium chloride solution (+ 0.1% TritonX-100).
  • test microbes are adjusted to a microbial count of 1 - 5 x 10 6 CFU/ml with 0.85% sodium chloride solution.
  • test substances are prepipetted at 8 ⁇ l per well into microtitre plates.
  • Prediluted microbial suspensions are diluted 1:100 in CASO broth and added at 192 ⁇ l per well to the test substances.
  • test mixtures are incubated at 37°C for 48 hours.
  • the growth is determined by reference to the clouding of the test mixtures (optical density) at 620 nm in a microplate reader.
  • the minimum inhibition concentration is the concentration of substance at which (compared with the growth control) a significant growth inhibition ( ⁇ 20% growth) of the test microbes is established.
  • One microtitre plate is prepared per test microbe and substance concentration. All of the substances are tested in duplicate.
  • Table 2 lists the results. The compounds correspond to those in Table 1 :

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Abstract

The use of benzyl alcohol derivatives of the formula CH2OH in which R,, R2, R3, n and m have the meanings given in claim 1, as microbicidal active sub­stances is described. The compounds exhibit a marked effect against pathogenic Gram-positive and Gram­negative bacteria. They are therefore suitable for the antimicrobial treatment, in particular preservation and disinfection, of surfaces.

Description

Benzyl alcohol derivatives
The present invention relates to the use of benzyl alcohol derivatives for the antimicrobial treatment of surfaces, as antimicrobial active substance against Gram-positive and Gram- negative bacteria, and preservation of cosmetics, household products, textiles, plastics and disinfectants, and also to novel benzyl alcohol derivatives.
The benzyl alcohol derivatives used according to the invention have the formula
(1) , in which
Figure imgf000002_0001
RLRJ. and R3, independently of one another, are unsubstituted C C20alkyl, C5.8cycloalkyl, C3-C20alkenyl or C C2oalkyl, C5-8cycloalkyl, C3-C20alkenyl substituted by d-C4alkyl, d -C4alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-C C2alkyl, amino, -NHCr C2oalkyl or -N(C1-C2oalkyl)2; C2-C20alkyl which is interrupted by one or more heteroatoms and/or may be substituted; C2-C20perfluoroalkyl; -(C^C^alkyleneJ-Si-^ris-d-^alkyl); -(C2-C12alkylene)-Si-(di-Cι.12alkyl)-C3-C12alkenyI; or -(CH2)x(CHCH3)y(C(CH3)2)z-A;
A is unsubstituted phenyl, naphthyl or C4-C8cycloalkyl or phenyl, naphthyl or C - C8cycloalkyl substituted by d-C4alkyl, d-C4alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-Cι-C2alkyl, amino, -NHd-C20alkyl or -N(d-C2oalkyl)2; or -CH2CH2(CH2CH2O)0-B;
B is unsubstituted C C4alkyl or phenyl or C C alkyl or phenyl substituted by d-C alkyl, d-C4alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-C C2alkyl, amino, -NHC C20alkyl or -N(C C20alkyl)2; o is an integer from 0 - 10; n and m, independently of one another, are 0 or 1 ; and x, y and z, independently of one another, are 0 to 12; and mixtures thereof and salts thereof, where compounds of the formula (1) in which
Ri and R2 or R^ and R3 or R2 and R3 are methyl or ethyl are not included.
The C2-C20alkyls interrupted by one or more heteroatoms are interrupted, in particular, by O, S or N. d-C20Alkyls are straight-chain or branched alkyl radicals, such as, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, de- cyl, undecyl, dodecyl, tetradecyl, pentadecyl or hexadecyl.
C C4Alkoxy is, for example, methoxy, ethoxy, n-propoxy, isopropoxy or n-butoxy. Halogen is fluorine, chlorine, bromine or iodine.
In preferred compounds used according to the invention,
Ri, R2 and R3, independently of one another, are unsubstituted C5-Cι6alkyl, C3-C6cycloalkyl or C3-Cι6alkenyl or C5-C16alkyl, C3-C6cycloalkyl or C3-C16alkenyl substituted by d- C4alkyl, d-C4alkoxy, hydroxy, phenyl, halogen, CN, COOH, COO-d-C2-alkyl, amino, NHCrC2oalkyl, N(C1-C20alkyl)2; C3-Cι6alkyl which is interrupted by one or more heteroatoms from the group O, N or S; Crdβperfluoroalkyl; -(d-C12alkylene)-Si-(tris-d-12alkyl); -(C1-C6alkylene)-Si-(di-C1-C2alkyl)allyl; -(CH2)x(CHCH3)y(C(CH3)2)z-A; or - CH2CH2(CH2CH2O)0-B;
A is unsubstituted phenyl or C5-C6cycloalkyl or phenyl or C5-C6cycloalkyl substituted by C^C^Ikyl, d-C4alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-CrC2alkyl, amino, NHCι-C20alkyl or N(CrC20alkyl)2;
B is unsubstituted Cι-C2alkyl or phenyl or CrC2alkyl or phenyl substituted by d-C4alkyl, C^C^Ikoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-d-C2alkyl, amino, NHC C20alkyl or N(d-C2oalkyl)2; x, y and z, independently of one another, are an integer from 0 to 4; o is an integer from 0 to 5; and n and m, independently of one another, are 0 or 1.
Interesting compounds which can be used according to the invention have the formula
(1a) , in which
Figure imgf000003_0001
Rt is
Figure imgf000003_0002
-CH2SiC6H5; -(CH2)5CH3; -(CH2)7CH3; -CH(CH2CH3)2; or -CH(CH3)(CH2)4CH3. Further interesting compounds which can be used according to the invention have the formulae
Figure imgf000004_0001
Ri is -(CH2)ι-3Si(CH3)3; -CH2Si(CH3)2(CH2CH=CH2); -CH2Si(CH3)2C6H5; linear C4-C10alkyl;
-CH(CH2CH3)2; -CH(CH3)(CH2)4CH3; -CH2CH2OC6H5; cyclohexyl; or -CH2C6H5; R2 is -d-C4alkyl;
Figure imgf000004_0002
-CH2Si(CH3)2(CH2CH=CH2); -CH2Si(CH3)2C6H5;
-(CH2)3CH3; -(CH2)5CH3; -(CH2)7CH3; -CH(CH2CH3)2; -CH(CH3)(CH2)4CH3;
-CH2CH2OC6H5; cyclohexyl; or -CH2C6H5.
Particularly preferred compounds of the formulae (1b) - (1f) are those in which
Ri is -CH2Si(CH3)3 -(CH2)3Si(CH3)3; -CH2Si(CH3)2(CH2CH=CH2); -CH2Si(CH3)2C6H5;
-(CH2)sCH3; -(CH2)7CH3; -CH(CH2CH3)2; -CH(CH3)(CH2) CH3; -CH2CH2OCβH5;
-(CH2)3CH3; cyclohexyl; or -CH2C6H5; and R2 is methyl.
Table 1 below lists examples of further compounds which can be used according to the invention:
Figure imgf000005_0001
Figure imgf000006_0001
Figure imgf000007_0001
Figure imgf000008_0001
Pref erred are the compounds of formulae (14), (28), (37), (38), (39) and (40).
Benzyl alcohol derivatives used according to the invention are prepared by known methods,
which comprises reacting a compound of the formula (2a) with a halide
Figure imgf000009_0001
Hal-Ri or a mixture of Hal-Rι/Hal-R2> Hal-Ri/Hal-Ra, Hal-R2/Hal-R3 or Hal-Rt/Hal-Ra/Hal-Rg, in which all substituents can have the meanings given in formula (1) and R' is hydrogen
or O-d-C3alkyl, to give a compound of the formula (2b) .
Figure imgf000009_0002
The compound of the formula (2b) is then converted, by reduction, into the compound of the formula (1).
The overall reaction can be represented by the following scheme:
Figure imgf000009_0003
(2a) (2b) (1)
The synthesis of the compounds of the formula (2b) is, in particular, carried out in a solvent, such as dimethylformamide, methanol, ethanol, acetone, acetonitrile or ethyl acetate, to which an (auxiliary) base, such as, for example, sodium hydride, sodium alkoxides or alkali metal carbonate, has been added, at a temperature of from 40 to 120°C, preferably 60 to 100°C. Per OH group of the compound of the formula (2a), preferably 1.1 equivalent of the halide Hal-Ri or a mixture of Hal-R1/Hal-R2, Hal-Ri/Hal-Rg, Hal-R2/Hal-R3 or Hal-RJHal-Ra/Hal-Rg is added. Preferred halides are chlorides and bromides.
The reaction time is 2 to 48 hours. A preferred reaction time is about 18 hours.
The reduction of the compounds of the formula (2b) to give compounds of the formula (1) is carried out in accordance with customary methods.
The reducing agents used are customary reducing agents, such as, for example, hydrogen, metal hydrides or dithionite.
The solvents used are, for example, diethyl ether or tetrahydrofuran.
The reducing agent is customarily added in a 10- to 20-fold excess.
The reaction temperature is usually between 20 and 50°C, preferably 25 to 45°C.
Further details relating to the preparation process are given in the corresponding examples.
The benzyl alcohols used according to the invention exhibit a marked antimicrobial effect, in particular against pathogenic Gram-positive and Gram-negative bacteria and also against skin flora bacteria. They are therefore suitable, in particular, for the disinfection, deodoriza- tion, and also the general and antimicrobial treatment of the skin and mucosae, and skin appendages (hair), very particularly for hand and wound disinfection. They are therefore suitable as antimicrobial active substances and preservatives in bodycare compositions, such as, for example, shampoos, bath products, haircare compositions, liquid and solid soaps (based on synthetic surfactants and salts of saturated and/or unsaturated fatty acids), lotions and creams, deodorants, other aqueous or alcoholic solutions, e.g. cleansing solutions for the skin, moist cleansing wipes, oils or powders.
The invention therefore further provides a bodycare composition comprising at least one compound of the formula (1) and cosmetically acceptable carriers or auxiliaries. The bodycare composition according to the invention comprises 0.01 to 15% by weight, preferably 0.1 to 10% by weight, based on the total weight of the composition, of the benzyl alcohol compound of the formula (I) and cosmetically acceptable auxiliaries.
Depending on the form in which the bodycare composition is present, as well as the benzyl alcohol compound of the formula (1), it also has further constituents, such as, for example, sequestering agents, dyes, perfume oils, thickening or setting agents (consistency regulators), emollients, UV-absorbers, skin protectants, antioxidants, additives which improve the mechanical properties, such as dicarboxylic acids and/or Al, Zn, Ca, Mg salts of C^-C^ fatty acids and optionally preservatives.
The bodycare composition according to the invention can be formulated as a water-in-oil emulsion or oil-in-water emulsion, as an alcoholic or alcohol-containing formulation, as a vesicular dispersion of an ionic or nonionic amphiphilic lipid, as a gel, solid stick or as an aerosol formulation.
As a water-in-oil or oil-in-water emulsion, the cosmetically acceptable auxiliary preferably comprises 5 to 50% of an oil phase, 5 to 20% of an emulsifier and 30 to 90% of water. The oil phase can comprise any oil suitable for cosmetic formulations, such as, for example, one or more hydrocarbon oils, a wax, a natural oil, a silicone oil, a fatty acid ester or a fatty alcohol. Preferred mono- or polyols are ethanol, isopropanol, propylene glycol, hexylene glycol, glycerol and sorbitol.
Cosmetic formulations according to the invention are used in various fields. In particular, the following compositions, for example, are considered: skincare compositions, such as, for example, skin washing and cleansing compositions in the form of bar or liquid soaps, syndets or washing pastes, bath preparations, such as, for example, liquid bath preparations (foam baths, milks, shower preparations) or solid bath preparations, such as, for example, bath tablets and bath salts; skincare compositions, such as, for example, skin emulsions, multiple emulsions or skin oils; decorative bodycare compositions, such as, for example, make-up for the face in the form of day or powder creams, face powder (loose and pressed), blusher or cream make-up, eyecare compositions, such as, for example, eyeshadow preparations, mascara, eyeliner, eye creams or eye-fix creams; lipcare compositions, such as, for example, lipstick, lip gloss, lip liner pencil, nailcare compositions, such as nail varnish, nail varnish remover, nail hardeners, or cuticle removers; intimate care compositions, such as, for example, intimate washing lotions or intimate sprays; footcare compositions, such as, for example, foot baths, foot powders, foot creams or foot balsams, especially deodorants and antiperspirants or compositions for removing hard skin; sunscreens, such as sun milks, lotions, creams, oils, sunblocks or tropicals, pretanning preparations or aftersun preparations; skin-tanning preparations, such as, for example, self-tanning creams; depigmentation compositions, such as, for example, skin bleaching preparations or skin lightening compositions; insect-repelling compositions ("repellants"), such as, for example, insect oils, lotions, sprays or sticks; deodorants, such as deodorant sprays, pump sprays, deodorant gels, sticks or roll-ons; antiperspirants, such as, for example, antiperspirant sticks, creams or roll-ons; compositions for the cleansing and care of blemished skin such as, for example, syn- dets (solid or liquid), peeling or scrub preparations or peeling masks; hair-removal compositions in chemical form (depilation), such as, for example, hair- removal powders, liquid depilatories, cream or paste depilatories, depilatories in gel form or aerosol foams; shaving compositions, such as, for example, shaving soap, foaming shaving creams, nonfoaming shaving creams, foams and gels, preshave preparations for dry shaving, aftershaves or aftershave lotions; fragrances, such as, for example, toilet waters (eau de Cologne, eau de toilette, eau de parfum, parfum de toilette, perfume), perfume oils or perfume creams; compositions for dental care, denture care and oral care, such as, for example, tooth creams, gel tooth creams, tooth powders, mouthwash concentrates, antiplaque mouth- washes, prothesis cleaners or prothesis adhesives; cosmetic compositions for hair treatment, such as, for example, hair cleansers in the form of shampoos, hair conditioners, haircare compositions, such as, for example, pre- treatment compositions, hair tonic, styling creams, styling gels, pomades, hair rinses, treatment packs, intensive hair treatments, compositions for shaping the hair, such as, for example, waving agents for producing permanent wave (hot-wave, mild-wave, cold- wave), hair-smoothing preparations, liquid hair-setting compositions, hair foams, hair sprays, blonding agents, such as, for example, hydrogen peroxide solutions, lightening shampoos, blonding creams, blonding powders, blonding pastes or oils, temporary, semipermanent or permanent hair colorants, preparations with self-oxidizing dyes, or natural hair colorants, such as henna or camomile.
An antimicrobial soap has, for example, the following composition: 0.01 to 5% by weight of the compound of the formula (1) 0.3 to 1 % by weight of titanium dioxide, 1 to 10% by weight of stearic stearic acid ad 100% of soap base, such as, for example, the sodium salts of tallow fatty acid and coconut fatty acid or glycerol.
A shampoo has, for example, the following composition: 0.01 to 5% by weight of the compound of the formula (1), 12.0% by weight of sodium laureth-2 sulphate,
4.0% by weight of cocamidopropylbetaine,
3.0% by weight of NaCI and ad 100% of water.
A deodorant has, for example, the following composition:
0.01 to 5% by weight of the compound of the formula (1 ),
60% by weight of ethanol,
0.3% by weight of perfume oil, and ad 100 % of water.
The invention further provides an oral composition comprising 0.01 to 15% by weight, based on the total weight of the composition, of the compound of the formula (1) and orally acceptable auxiliaries.
Example of an oral composition: 10% by weight of sorbitol, 10% by weight of glycerol,
15% by weight of ethanol,
15% by weight of propylene glycol,
0.5% by weight of sodium lauryl sulphate,
0.25% by weight of sodium methyl cocyltaurate,
0.25% by weight of polyoxypropylene/polyoxyethylene block copolymer,
0.10% by weight of peppermint flavouring,
0.1 to 0.5% by weight of a compound of the formula (I), and
48.6% by weight of water.
The oral composition according to the invention can be, for example, in the form of a gel, a paste, a cream or an aqueous preparation (mouthwash).
In addition, the oral composition according to the invention can comprise compounds which release fluoride ions, which are effective against the formation of caries, e.g. inorganic fluoride salts, such as, for example, sodium fluoride, potassium fluoride, ammonium fluoride or calcium fluoride, or organic fluoride salts, such as, for example, amine fluorides, which are known under the trade name Olafluor.
In addition, the benzyl alcohol derivatives of the formula (1) used according to the invention are suitable for the treatment, in particular preservation, of textile fibre materials. The fibre materials are undyed and dyed or printed and are made of, for example, silk, wool, polyam- ide or polyurethanes, and in particular cellulosic fibre materials of all types. Such fibre materials are, for example, natural cellulose fibres, such as cotton, linen, jute and hemp, and also regenerated cellulose. Preferred suitable textile fibre materials are made of cotton.
The benzyl alcohols according to the invention are also suitable for the treatment, in particular for the antimicrobial finishing or preservation, of plastics, such as, for example, polyethylene, polypropylene, polyurethane, polyester, polyamide, polycarbonate, latex etc.. Fields of use for these are, for example, floor coverings, plastic coatings, plastic container and packaging materials; kitchen and bathroom utensils (e.g. brushes, shower curtains; sponges, bathroom mats), latex, filter materials (air and water filters), plastic articles used in the medical sector, such as, for example, bandaging materials, syringes, catheters etc., so-called medical devices, gloves and mattresses. Paper too, such as, for example, hygiene papers, can be antimicrobially finished with the benzyl alcohols according to the invention.
In addition, nonwovens, such as, for example, nappies, sanitary towels, panty liners, wipes for the hygiene and household sector, can be antimicrobially finished according to the invention.
In addition, the benzyl alcohols of the formula (1) are used in washing and cleaning formulations, such as, for example, in liquid and powder detergents or fabric softeners.
The benzyl alcohols can be used, in particular, also in household and all-purpose cleaners for the cleaning and disinfection of hard surfaces. A cleaner has, for example, the following composition:
0.01 to 5% of the compound of the formula (1)
3.0% of octyl alcohol 4EO
1.3% of fatty alcohol C8-C10 polyglucoside
3.0% of isopropanol ad 100% of water.
As well as the preservation of cosmetics and household products, the preservation and antimicrobial finishing of technical products and also use as biocide in technical processes is also possible, such as, for example, in the treatment of paper, in particular in paper- treatment liquors, printing thickeners made of starch or cellulose modifications, surface coatings and paints.
The benzyl alcohols of the formula (1) are also suitable for the antimicrobial treatment of wood and also for the antimicrobial treatment, preservation and finishing of leather.
In addition, the compounds according to the invention are suitable for protecting cosmetic products and household products against microbial decay. The benzyl alcohols which can be used according to the invention are known compounds or novel compounds.
The novel compounds have the above formula
(1*) , in which
Figure imgf000016_0001
R'ι,R'2 and R'3, independently of one another, are unsubstituted d-C20alkyl, C5.8cycloalkyl, C3-C20alkenyl or CrC20alkyl, C5.8cycloalkyl, Cjr-doalkenyl substituted by C1-C4alkyl, d -dalkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-Cι-C2alkyl, amino, -NHCr C20alkyl or -N(C1-C20alkyl)2; C2-C20alkyl which is interrupted by one or more heteroatoms and/or may be substituted; C2-C20perfluoroalkyl; -(C2-C12alkylene)-Si-(tris-C1.i2alkyl); -(C2-C12alkylene)-Si-(di-C1.12alkyl)-C3-C12alkenyl; or -(CH2)x(CHCH3)y(C(CH3)2)z-A;
A is unsubstituted phenyl, naphthyl or C4-C8cycloalkyl or phenyl, naphthyl or C4-
C8cycloalkyl substituted by d-C4alkyl, d-C4alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-d-C2alkyl, amino, -NHC C20alkyl or -N(C1-C20alkyl)2; or -CH2CH2(CH2CH2O)0-B;
B is unsubstituted d-C4alkyl or phenyl or C C4alkyl or phenyl substituted by d-C4alkyl, d-C4alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-d-C2alkyl, amino, -NHCr C20alkyl or -N(d-C20alkyl)2; o is an integer from 0 - 10; n and m, independently of one another, are 0 or 1 ; and x, y and z, independently of one another are 0 to 12; with the proviso that if n and m are 0, is not an alkyl group, if R't is methyl or ethyl and either n or m is 1 , then R'2 or R'3 is not a methyl or benzyl group, and if R'i is a linear C12alkyl group and either n or m is 1 , then R'2 or R'3 is not a linear C12alkyl group.
The examples below, which do not limit the invention, are used for illustration. Example 1 :
In a reaction vessel with attached condenser and stirrer, 10g (82mmol) of 4- hydroxybenzyldehyde and 11.3g (82mmol) of dried potassium carbonate are initially introduced into 60ml of dry dimethylformamide, and 17.4g (90mmol) of n-octyl bromide are added. The mixture is stirred for 18 hours at 80°C. After the solvent has been stripped off at 10' 2 mbar, the residue is taken up in 100ml of water and 50ml of petroleum ether, the organic phase is separated off, dried and then the solvent is stripped off. The intermediate can be used subsequently without further purification steps.
For the reduction, 2.5g (67mmol) of lithium aluminium hydride are initially introduced into 200ml of diethyl ether, and, at room temperature, the solution of 15.7g (67mmoI) of the precursor in 50ml of diethyl ether is added dropwise thereto. The reaction mass is refluxed for 6 hours and, after cooling, carefully transferred dropwise to 200ml of water. Following acidification of the aqueous phase with concentrated hydrochloric acid to pH 2, the organic phase is separated off, washed with water until neutral and evaporated. The crystalline residue is recrystallized from a small amount of n-hexane.
The resulting colourless crystals which correspond to the compound of the formula
Figure imgf000017_0001
(= compound (9) in Table 1), are obtained in a yield of 62%.
The purity is 97 area % LC(254nm).
The recorded 1H/13C-NMR spectra confirm the structure.
The other compounds in Table 1 can be prepared analogously to Synthesis Example 1 using the respective starting materials. Determination of the minimum inhibition concentration (MIC value) in microtitre plates
Nutrient medium:
Casein-soy flour-peptone broth for the preparation of the precultures of the test bacteria and yeast.
Examples of test microbes: Bacteria: Staphylococcus aureus ATCC 6538 Escherichia coli NCTC 8196 (= EC)
Procedure:
The test substances are predissolved in dimethyl sulphoxide (DMSO) and tested in a dilution series of 1 :2.
The bacteria are cultivated overnight in CASO broth and sponged off with 10 ml of 0.85% sodium chloride solution (+ 0.1% TritonX-100).
All of the test microbes are adjusted to a microbial count of 1 - 5 x 106 CFU/ml with 0.85% sodium chloride solution.
The test substances are prepipetted at 8 μl per well into microtitre plates.
Prediluted microbial suspensions are diluted 1:100 in CASO broth and added at 192 μl per well to the test substances.
The test mixtures are incubated at 37°C for 48 hours.
After incubation, the growth is determined by reference to the clouding of the test mixtures (optical density) at 620 nm in a microplate reader.
The minimum inhibition concentration (MIC value) is the concentration of substance at which (compared with the growth control) a significant growth inhibition (< 20% growth) of the test microbes is established. One microtitre plate is prepared per test microbe and substance concentration. All of the substances are tested in duplicate.
Table 2 lists the results. The compounds correspond to those in Table 1 :
Figure imgf000019_0001
Figure imgf000020_0001

Claims

WHAT IS CLAIMED IS:
1. The use of compounds of the formula
(1) , in which
Figure imgf000021_0001
R1(R2 and R3, independently of one another, are unsubstituted C C20alkyl, C5^cycloalkyl, C3-C20alkenyl or C C20alkyl, C5.8cycloalkyl, d-Cajalkenyl substituted by d-C4alkyl, Ci -C4alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-CrC2alkyl, amino, -NHd- C20alkyl or -N(Cι-C20alkyl)2; C2-C20alkyl which is interrupted by one or more heteroatoms and/or may be substituted; C2-C20perfluoroalkyl; -(C2-C12alkylene)-Si-(tris-d.12alkyl); -(C2-C12alkylene)-Si-(di-C1.12alkyl)-C3-C12alkenyl; or -(CH2)x(CHCH3)y(C(CH3)2)z-A;
A is unsubstituted phenyl, naphthyl or C4 -C8cycloalkyl or phenyl, naphthyl or C4 - C8cycloalkyl substituted by C1-C4alkyl, C1-C4alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-d-C2alkyl, amino, -NHC C20alkyl or -N(d-C20alkyl)2; or -CH2CH2(CH2CH2O)o-B;
B is unsubstituted C C4alkyl or phenyl or CrC4alkyl or phenyl substituted by d-C4alkyl, d-C4alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-C C2alkyl, amino, -NHd- C20alkyl or -N(C C20alkyl)2; o is an integer from 0 - 10; n and m, independently of one another, are 0 or 1 ; and x, y and z, independently of one another, are 0 to 12; and mixtures thereof and salts thereof, where compounds of the formula (1) in which
Ri and R2 or Ri and R3 or R2 and R3 are methyl or ethyl are not included; for the antimicrobial treatment of surfaces.
2. The use according to claim 1 , wherein
R1f R2 and R3, independently of one another, are unsubstituted C5-C16alkyl, C3-C6cycloalkyl or C3-C16alkenyl or C5-C16alkyl, C3-C6cycloalkyl or C3-C16alkenyl substituted by Ci- C4alkyl, d-C4alkoxy, hydroxy, phenyl, halogen, CN, COOH, COO-d-C2-alkyl, amino, NHd-C20alkyl, N(d-C20alkyl)2; C3-C16alkyl which is interrupted by one or more heteroatoms from the group O, N or S; d-deperfluoroalkyl; -(Cι-C12alkylene)-Si-(tris-Cι.ι2alkyl); -(CrC6alkylene)-Si-(di-Cι-C2alkyl)allyl; -(CH2)x(CHCH3)y(C(CH3)2)z-A; or
-CH2CH2(CH2CH2O)o-B; A is unsubstituted phenyl or C5-Cβcycloalkyl or phenyl or C5-C6cycloalkyl substituted by
Cι-C4alkyl, Cι-C4alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-d-C2alkyl, amino, NHC C20alkyl or N(Cι-C20alkyl)2; B is unsubstituted d-C2alkyl or phenyl or d-C2alkyl or phenyl substituted by Cι-C4alkyl,
Cι-C4alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-d-C2alkyl, amino, NHd-
C20alkyl or N(CrC20alkyl)2; x, y and z, independently of one another, are an integer from 0 to 4; o is an integer from 0 to 5; and n and m, independently of one another, are 0 or 1.
3. The use according to claim 1 or 2, wherein compounds of the formula
(1a) , in which
Figure imgf000022_0001
Ri is -(CH2)^Si(CH3)3; -CH2Si(CH3)2(CH2CH=CH2); -CH2SiC6H5; -(CH2)5CH3; -(CH2)7CH3;
-CH(CH2CH3)2; or -CH(CH3)(CH2)4CH3; are used.
4. The use according to claim 1 or 2, wherein compounds of the formulae
Figure imgf000022_0002
(1f) in which
Figure imgf000022_0003
Ri is -(CH2)^Si(CH3)3; -CH2Si(CH3)2(CH2CH=CH2); -CH2Si(CH3)2C6H5; linear C4-Cιoalkyl; -CH(CH2CH3)2; -CH(CH3)(CH2)4CH3; -CH2CH2OC6H5; cyclohexyl; or -CH2C6H5; R2 is -d-C4alkyl; -(CHa aS CHg -CH2Si(CH3)2(CH2CH=CH2); -CH2Si(CH3)2C6H5; -(CH2)3CH3; -(CH2)5CH3; -(CH2)7CH3; -CH(CH2CH3)2; -CH(CH3)(CH2)4CH3; -CH2CH2OC6H5; cyclohexyl; or -CH2C6H5; are used.
5. The use according to claim 4, wherein
Ri is -CH2Si(CH3)3 -(CH2)3Si(CH3)3; -CH2Si(CH3)2(CH2CH=CH2); -CH2Si(CH3)2C6H5;
-(CH2)5CH3; -(CH2)7CH3; -CH(CH2CH3)2; -CH(CH3)(CH2)4CH3; -CH2CH2OC6H5;
-(CH2)3CH3; cyclohexyl; or -CH2C6H5; and R2 is methyl.
6. A process for the preparation of the compounds of the formula (1) according to claim 1 , which comprises reacting a compound of the formula (2a)
Figure imgf000023_0001
with a halide Hal-Ri or a mixture of Hal-R1/Hal-R2, Hal-Ri/Hal-Rs, Hal-R2/Hal-R3 or Hal- Rι/Hal-R2/Hal-R3 to give the compound of the formula (2b)
Figure imgf000023_0002
and then converting it, by reduction, into the compound of the formula (1) according to claim 1 in accordance with the following scheme: Hal-RJHal-Fξ, Hal-RJHal-R,
Hal-RJΗal-R,
3 Reduction
Figure imgf000024_0001
Figure imgf000024_0002
Figure imgf000024_0003
(2a) (2b) (1) in which
R' is hydrogen or O-Cι-C5alkyl, and Riι R2, Re. m and n have the meanings given in claim 1.
7. The use of the compound of the formula (1) for the antimicrobial treatment, deodorization and disinfection of the skin, mucosae and hair.
8. The use according to claim 7, wherein the compound of the formula (1) is used for disinfection and deodorization.
9. The use of the compound of the formula (1) for the treatment of textile fibre materials.
10. The use according to claim 9, wherein the compound of the formula (1) is used for preservation.
11. The use of the compound of the formula (1) in washing and cleaning formulations.
12. The use of the compound of the formula (1) for the antimicrobial finishing and preservation of plastics, paper, nonwovens, wood or leather.
13. The use of the compound of the formula (1) for the antimicrobial finishing and preservation of technical products, in particular printing thickeners made of starch or cellulose modifications, surface coatings and paints.
14. The use of the compound of the formula (1) as biocide in technical processes.
15. A bodycare composition comprising
0.01 to 15% by weight, based on the total weight of the composition, of the compound of the formula (1) and cosmetically acceptable auxiliaries.
16. An oral composition comprising 0.01 to 15% by weight, based on the total weight of the composition, of the compound of the formula (1) and orally acceptable auxiliaries.
17. A compound of the formula
(1 ') , in which
Figure imgf000025_0001
R'ι,R'2 and R'3, independently of one another, are unsubstituted d-C20alkyl, C5.8cycloalkyl, C3-C20alkenyl or Cι-C20alkyl, C5.8cycloalkyl, Cs-C^alkenyl substituted by Cι-C4alkyl, Cι -dalkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-d-C2alkyl, amino, -NHd- C20alkyl or -N(Cι-C20alkyl)2; C2-C20alkyl which is interrupted by one or more heteroatoms and/or may be substituted; C2-C2operfluoroalkyl; -(C2-Cι2alkylene)-Si-(tris-Cι.12alkyl); -(C2-Ci2alkylene)-Si-(di-Ci.i2alkyl)-C3-Ci2alkenyl; or -(CH2)x(CHCH3)y(C(CH3)2)2-A;
A is unsubstituted phenyl, naphthyl or C4-C8cycloalkyl or phenyl, naphthyl or C4-
Cscycloalkyl substituted by Cι-C alkyl, Cι-C4alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-CrC2alkyl, amino, -NHCrC20alkyl or -N(CrC20alkyl)2; or -CH2CH2(CH2CH2O)0-B;
B is unsubstituted C C alkyl or phenyl or d-C alkyl or phenyl substituted by Cι-C4alkyl, d-C4alkoxy, hydroxy, phenyl, halogen, -CN, -COOH, -COO-CrC2alkyl, amino, -NHC C20alkyl or -N(CrC20alkyl)2; o is an integer from 0 - 10; n and m, independently of one another, are 0 or 1 ; and x, y and z, independently of one another are 0 to 12; and mixtures thereof and salts thereof, with the proviso that if n and m are 0, R'ι is not an alkyl group, if R'ι is methyl or ethyl and either n or m is 1 , then R'2 or R'3 is not a methyl or benzyl group, and if R'ι is a linear C12alkyl group and either n or m is 1 , then R'2 or R'3 is not a linear Cι2alkyl group.
PCT/EP2003/002618 2002-03-19 2003-03-13 Benzyl alcohol derivatives and their use as antimicrobial agents WO2003078367A2 (en)

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JP2003576376A JP2005520829A (en) 2002-03-19 2003-03-13 Benzyl alcohol derivative
AU2003208707A AU2003208707A1 (en) 2002-03-19 2003-03-13 Benzyl alcohol derivatives and their use as antimicrobial agents
EP03706613A EP1485339A2 (en) 2002-03-19 2003-03-13 Benzyl alcohol derivatives and their use as antimicrobial agents

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9687429B2 (en) 2007-06-20 2017-06-27 The Trustees Of Columbia University In The City Of New York Antimicrobial compositions containing low concentrations of botanicals
US9968101B2 (en) 2011-11-03 2018-05-15 The Trustees Of Columbia University In The City Of New York Botanical antimicrobial compositions
CN108086050A (en) * 2017-12-18 2018-05-29 江西晶安新资源有限公司 A kind of potassium zirconium carbonate crosslinking water repellent agent and preparation method thereof
CN108086047A (en) * 2017-12-18 2018-05-29 江西晶安新资源有限公司 A kind of high solids content zirconium carbonate ammonium crosslinking water repellent agent and preparation method thereof
US9981069B2 (en) 2007-06-20 2018-05-29 The Trustees Of Columbia University In The City Of New York Bio-film resistant surfaces
US10542760B2 (en) 2007-06-20 2020-01-28 The Trustees Of Columbia University In The City Of New York Skin and surface disinfectant compositions containing botanicals
US10806144B2 (en) 2011-11-03 2020-10-20 The Trustees Of Columbia University In The City Of New York Composition with sustained antimicrobial activity

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4663314A (en) * 1985-05-16 1987-05-05 Shionogi & Co., Ltd. Ether compounds carrying substituted silyl group
US4668705A (en) * 1983-09-09 1987-05-26 Henkel Kommanditgesellschaft Auf Aktien Sebosuppressive preparations containing alkoxyaryl alkanols
US4946865A (en) * 1985-12-27 1990-08-07 Sumitomo Chemical Company, Limited Dipropargyloxybenzene compounds and their production
US5391817A (en) * 1993-12-21 1995-02-21 Bristol-Myers Squibb Biaryl phospholipase A2 inhibitors
WO1998001524A1 (en) * 1996-07-03 1998-01-15 Unilever Plc Antimicrobial cleaning compositions containing aromatic alcohols or phenols
EP0908553A2 (en) * 1997-10-13 1999-04-14 Ciba SC Holding AG Process for the treatment of textile materials with an antimicrobial agent
EP1053989A2 (en) * 1999-05-20 2000-11-22 Ciba SC Holding AG Hydroxydiphenyl ether compounds
WO2001062082A2 (en) * 2000-02-23 2001-08-30 Ciba Specialty Chemicals Holding Inc. Use of phenylethylamine derivatives for the anitmicrobial treatment of surfaces

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2000191520A (en) * 1998-12-31 2000-07-11 Kazuo Sakuma Microbicide

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4668705A (en) * 1983-09-09 1987-05-26 Henkel Kommanditgesellschaft Auf Aktien Sebosuppressive preparations containing alkoxyaryl alkanols
US4663314A (en) * 1985-05-16 1987-05-05 Shionogi & Co., Ltd. Ether compounds carrying substituted silyl group
US4946865A (en) * 1985-12-27 1990-08-07 Sumitomo Chemical Company, Limited Dipropargyloxybenzene compounds and their production
US5391817A (en) * 1993-12-21 1995-02-21 Bristol-Myers Squibb Biaryl phospholipase A2 inhibitors
WO1998001524A1 (en) * 1996-07-03 1998-01-15 Unilever Plc Antimicrobial cleaning compositions containing aromatic alcohols or phenols
EP0908553A2 (en) * 1997-10-13 1999-04-14 Ciba SC Holding AG Process for the treatment of textile materials with an antimicrobial agent
EP1053989A2 (en) * 1999-05-20 2000-11-22 Ciba SC Holding AG Hydroxydiphenyl ether compounds
WO2001062082A2 (en) * 2000-02-23 2001-08-30 Ciba Specialty Chemicals Holding Inc. Use of phenylethylamine derivatives for the anitmicrobial treatment of surfaces

Non-Patent Citations (6)

* Cited by examiner, † Cited by third party
Title
A. NAKAZATO ET AL: "Design, synthesis, structure-activity relationships, and biological characterization of novel arylalkoxyphenylalkylamine sigma ligands as potential antipsychotic drugs" JOURNAL OF MEDICINAL CHEMISTRY, vol. 42, no. 6, 1999, pages 1076-1087, XP002218375 WASHINGTON US *
CHEMICAL ABSTRACTS, vol. 53, no. 19, 10 October 1959 (1959-10-10) Columbus, Ohio, US; E PROFFT: "o-Vanilin and novovanillin (2-hydroxy-3-ethoxybenzaldehyde). II. 2,3-Dialkoxyphenyl-beta-ethylamines" column 17941e; XP002218376 & ARCH. PHARM., vol. 292, 1959, pages 70-75, *
D. REHN UND H. NOLTE: "Zur antimikrobiellen Wirksamkeit subtituierter aromatischer Aldehyde und Alkohole" ZBL. BAKT. HYG., I. ABT. ORIG. B, vol. 168, 1979, pages 507-516, XP000617375 *
DATABASE WPI Section Ch, Week 0050 Derwent Publications Ltd., London, GB; Class B05, AN 2000-545825 XP002261555 & JP 2000 191520 A (SAKUMA) *
H. . SHAM ET AL: "A novel, picomolar inhibitor of human immunodeficiency virus type 1 protease" JOURNAL OF MEDICINAL CHEMISTRY, vol. 39, no. 2, 1996, pages 392-397, XP002218373 WASHINGTON US *
K. TANAKA ET AL: "Asymmetric reduction with 5-deazaflavin. II. Synthesis of some chiral 5-deazaflavin derivatives" CHEMICAL AND PHARMACEUTICAL BULLETIN., vol. 38, no. 2, 1990, pages 312-317, XP002218374 TOKYO JP *

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9687429B2 (en) 2007-06-20 2017-06-27 The Trustees Of Columbia University In The City Of New York Antimicrobial compositions containing low concentrations of botanicals
US9981069B2 (en) 2007-06-20 2018-05-29 The Trustees Of Columbia University In The City Of New York Bio-film resistant surfaces
US10542760B2 (en) 2007-06-20 2020-01-28 The Trustees Of Columbia University In The City Of New York Skin and surface disinfectant compositions containing botanicals
US9968101B2 (en) 2011-11-03 2018-05-15 The Trustees Of Columbia University In The City Of New York Botanical antimicrobial compositions
US10806144B2 (en) 2011-11-03 2020-10-20 The Trustees Of Columbia University In The City Of New York Composition with sustained antimicrobial activity
CN108086050A (en) * 2017-12-18 2018-05-29 江西晶安新资源有限公司 A kind of potassium zirconium carbonate crosslinking water repellent agent and preparation method thereof
CN108086047A (en) * 2017-12-18 2018-05-29 江西晶安新资源有限公司 A kind of high solids content zirconium carbonate ammonium crosslinking water repellent agent and preparation method thereof

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CN1642890A (en) 2005-07-20
WO2003078367A3 (en) 2004-07-29
US20050124579A1 (en) 2005-06-09

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