WO1999031036A2

WO1999031036A2 - O-derivatives of halogenated diphenyl ether compounds

Info

Publication number: WO1999031036A2
Application number: PCT/EP1998/007997
Authority: WO
Inventors: Werner Hölzl; Dietmar Hüglin; Thomas Maier; Jianwen Mao; Dietmar Ochs
Original assignee: Ciba Specialty Chemicals Holding Inc.
Priority date: 1997-12-12
Filing date: 1998-12-09
Publication date: 1999-06-24
Also published as: WO1999031036A3; AU2052599A; EP1042265A2

Abstract

The invention describes O-derivatives of halogenated diphenyl ether compounds of formula (1), in which R1 and R2 independently of one another are F, Cl or Br; Y is a radical of formula (1a); (1b); (1c); (1d); (1e) or (1f); R3 is C1-C22alkyl; C1-C22alkoxy; phenyl; phenyl-C1-C4alkyl; --(CH2)p4-A+R5R6R7; the radical of formula (I); R4 C1-C22alkyl; R5, R6, R7 and R8 independently of one another are hydrogen; C1-C4alkyl; sulfo-C1-C4alkyl; or R5 and R6 together with A form a cyclic radical unsubstituted or substituted by sulfo groups; or R7 and R8 together with N form a cyclic radical unsubstituted or substituted by sulfo groups; A is N or P; Z1 is fluorine, chlorine, the radical of formula (1g); Z2 is fluorine, chlorine, C1-C22alkoxy, C1-C22alkylthio or C1-C22-monoalkylamino or C1-C22dialkylamino; each of which is unsubstituted or substituted by OH, NH2 or sulfo; C6-C12aryloxy, C6-C12arylthio or C6-C12monoarylamino or C6-C12diarylamino, each of which is unsubstituted or substituted by OH, NH2 or sulfo; m is from 1 to 3; n is 1 or 2; and p1, p2, p3, p4 and p5 independently of one another are 1-4. The diphenyl ether derivatives according to the invention have excellent antimicrobial properties and are stable to migration.

Description

O-Derivatives of halogenated diphenyl ether compounds

The present invention relates to O-derivatives of halogenated diphenyl ether compounds, to a process for the preparation of these compounds, to their use as antimicrobial active substance.

It is known that certain halogenated diphenyl ether compounds have an excellent antimicrobial activity. These compounds are therefore widely used, for example as active substances for the antimicrobial finishing of medical items and household articles, as detergent additive and in the hygiene sector, for example in soaps or dental hygiene products. Polymeric materials can be antimicrobially finished by incorporating halogenated diphenyl ether compounds, the active substances being, as a result of their excellent migration properties, constantly conveyed to the surface of the corresponding material ("slow release"). For certain industrial applications, this effect is undesired since the long-term effect of antimicrobially finished materials such as textiles, paper, plastics, cellulose sponges etc. is reduced at the same time.

The object of the present invention is thus to provide diphenyl ether compounds which have antimicrobial activity and which, at the same time, are stable to migration.

Surprisingly, it has been found that certain derivatives of halogenated diphenyl ether compounds satisfy this requirement.

The present invention thus provides O-derivatives of halogenated diphenyl ether compounds of the formula

in which

R, and R₂ independently of one another are F, CI or Br; is a radical of the formula (1 a) -(CH₂) — CH - 0-R₄ ; (1 b)

(^{1 c}) -(CH₂)

O ^R5 or (1 f) _ p _ o - (CH₂) - N - R₆ • O R₇

R₃ is C C₂₂alkyl; C.-C^ alkoxy; phenyl; phenyl-C.-C^lkyl; — (CH₂)_p - A⁺R₅R₆R₇ ;

4

. the radical of the formula ;

I

COO^'

R₄ 0,-0₂₂311^1;

R₅, R₆, R₇ and R₈ independently of one another are hydrogen; C₁-C₄all yl; sulfo- C^C^Ikyl; or R₅ and R₆ together with A form a cyclic radical unsubstituted or substituted by sulfo groups; or R₇ and R₈ together with N form a cyclic radical unsubstituted or substituted by sulfo groups;

A is N or P;

Z, is fluorine, chlorine, the radical of the formula (1 g)

(R₂)n

Z₂ is fluorine, chlorine, d-Caaalkoxy, C C₂₂alkylthio or CrC₂₂-monoalkylamino or

C C-aadialkylamino; each of which is unsubstituted or substituted by OH, NH₂ or sulfo; C₆-C₁₂aryloxy, C₆-C₁₂arylthio or C₆-Cι₂monoarylamino or C₆-C₁₂diarylamino, each of which is unsubstituted or substituted by OH, NH₂ or sulfo; m is from 1 to 3; n is 1 or 2; and p p₂, p_3> p₄ and p₅ independently of one another are 1-4.

C.-C^alkyl and C^C^alkoxy are straight-chain or branched alkyl radicals, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, tert-butyl, amyl, isoamyl or tert-amyl, hexyl, heptyl, octyl, isooctyl, nonyl, decyl, undecyl, dodecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl or eicosyl, and methoxy, ethoxy, propoxy, butyloxy, pentyloxy, amyloxy, isoamyloxy, heptyloxy, octyloxy, isooctyloxy, nonyloxy, decyloxy, undecyloxy, dodecyloxy, tetradecyloxy, pentadecyloxy, hexadecyloxy, heptadecyloxy, octadecyloxy or eicosyloxy respectively.

Phenyl-C₁-C₄all<yl is, for example, phenylethyl, phenylpropyl, phenylbutyl or, preferably, benzyl.

The derivatives according to the invention are ester, ether or glucoside derivatives of halogenated diphenyl compounds.

Preferred ester derivatives are those of the formula

in which R_1t R₂, R₃, m and n are as defined in formula (1).

Particular preference is given to compounds of the formula (2) in which

R₃ is C.,-C₁₂alkyl; or phenyl; and, in particular, to those compounds of the formula (2) in which

R, and R₂ are chlorine;

R₃ is C.-C^alkyl; m is 1 or 2; and n is 1; Illustrative ester derivatives of halogenated diphenyl compounds according to the invention are those of the formula

in which R₃ is C^C^alkyl or phenyl.

Other suitable ester derivatives according to the invention are those of the formulae: o β n 8

(4) _A_ ₀j^ _ _Rg ; (5) _A_₀_^ _ _R

CH R CH-

10 10

(6) ^■

in which

is the radical of the formula (1 h) ; or, preferably,

R_v R₂, m and n are as defined in formula (1); and R₈, R₉ and R₁₀ independently of one another are hydrogen; or C.-C₄alkyl.

Preferred ether derivatives according to the invention are those of the formula

CH

in which

R R₂, R₄, X, m, n, p, and p₂ are as defined in formula (1 )

Very particularly preferred ether derivatives are those of the formula

in which

R₄ is C₁-C22alkyl. or of the formula

Other ether derivatives according to the invention are those of the formulae (12) v-0 — ,

in which

V is a radical of the formula (1 h), preferably (1 i) or (1 k); R₈, R₉ and R₁₀ are hydrogen; or C^C^Ikyl; and Z, is -O-V; and Z₂ is CI; or N(CH₂CH₂OH)₂.

Preferred glucoside derivatives according to the invention are those of the formula

in which

V is a radical of the formula (1 h), or, preferably, (1 i) or (1 k).

The halogenated diphenyl ether derivatives according to the invention which have a phosphate, sulfate or glucoside group are hydrophilic compounds, which are readily obtainable synthetically in high yields.

Compounds of the formula (1 ) in which

Y is a radical of the formula (1b);

R₃ is -(CH₂)_p4-N⁺R₅R6R₇; are obtained in good yields by reacting the chloroacetate of the compound of the formula

with primary, secondary and tertiary amines. The preparation of these compounds when R₃ is -(CH₂)p₄-P⁺R₅R₆R is analogous.

Sulfobetaines, i.e. compounds of the formula (1), in which

Y is a radical of the formula (1 b); R₃ is -(CH₂)_p4-A-N⁺R₅R₆R₇;

R₅ is sulfoalkyl; or R₅and R₆ with A form a cyclic radical, are obtained by reacting corresponding N-dialkyl- or -monoalkylbetaine esters of the compound of the formula (15) with aqueous MSO₃ solution and a suitable catalyst system.

Compounds of the formula (1) in which

Y is a radical of the formula (1f); and

are obtainable, for example, by reacting the compound of the formula (15) with ethylene

chlorophosphate, the compound of the formula _• ^anc* corresponding amine.

The glucoside derivatives (compounds of the formula (14)) are obtainable by reacting the phenolic OH group of the compound of the formula (15) with peracetylated glucose and subsequently hydrolyzing the ester protective groups.

The hydrophilic derivatives are colourless, high-melting compounds having good solubility in water.

Hydrophobic halogenated diphenyl ether derivatives, for example compounds of the formulae (3a), (3b), (10a), (10b) and (11a) and (11b) are obtainable in a single-stage reaction by esterifying or etherifying the phenolic OH group of the compound of the formula (15). Solubility and melting point of the acylated derivatives can be varied within a wide range by the choice of reactant.

Compounds of the formula (1), in which Y is a radical of the formula (1 a) or (1 c); R R₂, m and n are as defined in formula(1), can be obtained by etherification of the phenolic OH group of the compound of the formula

with the corresponding halide compound.

The diphenyl ether derivatives according to the invention are thermally stable and antimicrobially effective compounds of low volatility and having a severely reduced tendency to migrate. They are therefore preferably suitable for the antimicrobial finishing of polymeric compounds, for example in plastics, rubbers, paints, surface coatings, (textile) fibres which are exposed to a microbially contaminated environment.

Examples of polymers and other substrates which can be antimicrobially finished in this way are:

- polymers of mono- and diolefins,

- polyolefins,

- copolymers of mono- and diolefins with one another or with other vinyl monomers,

- hydrocarbon resins,

- polystyrene,

- copolymers of styrene or α-methylstyrene or dienes or acrylic derivatives,

- graft copolymers of styrene or α-methylstyrene.

- halogen-containing polymers,

- polymers derived from α,β-unsaturated acids and derivatives thereof, such as polyacrylates and polymethacrylates,

- polymers derived from unsaturated alcohols and amines or acyl derivatives or acetals thereof,

- homo- and copolymers of cyclic ethers, polyacetals, polyphenylene oxides and polyphenylene sulfides and mixtures thereof with styrene polymers or polyamides,

- polyurethanes derived from polyethers, polyesters and polybutadienes having terminal hydroxyl groups on the one hand and aliphatic or aromatic polyisocyanates on the other, and precursors thereof, - polyamides and copolyamides derived from diamines and dicarboxylic acids and/or from aminocarboxylic acids or the corresponding lactams,

- polyureas, polyimides, polyamide-imides. poiyetherimides, polyesterimides, polyhydantoins and polybenzimidazoles,

- polyesters,

- polycarbonates and polyester carbonates,

- polysulfones, polyether sulfones and polyether ketones,

- crosslinked polymers derived from aldehydes on the one hand and phenols, urea or melamine on the other hand, such as phenol-formaldehyde resins, urea-formaldehyde resins and melamine-formaldehyde resins,

- drying and non-drying alkyd resins,

- unsaturated polyester resins,

- crosslinkable acrylic resins,

- alkyd resins, polyester resins and acrylate resins,

- crosslinked epoxy resins,

- natural polymers, such as cellulose, natural rubber, gelatine, and derivatives thereof modified chemically in a polymer-homologous manner, such as cellulose acetates, cellulose propionates cellulose butyrates, or the cellulose ethers, such as methylcellulose; and also rosins and derivatives.

The invention thus also provides a composition comprising

(A) an organic material to be antimicrobially finished and

(B) a compound of the formula (1 ).

The invention also relates to a process for the antimicrobial finishing of an organic material, which comprises adding at least one compound of the formula (1 ) thereto, and to the use of the compound of the formula (1) for the antimicrobial finishing of polymeric materials.

The amount of antimicrobial active substance to be used depends on the organic material to be antimicrobially finished and on the intended use of the material finished in this way. The composition according to the invention generally comprises, per 100 parts by weight of component (A), from 0.01 to 15 parts by weight, in particular from 0.05 to 10 parts by weight, and especially from 0.1 to 5 parts by weight of the antimicrobial active substance (component (B)). The antimicrobial active substance (component (B)) can also be a mixture of two or more compounds of the formula (1). The compositions according to the invention can, in addition to the compounds according to the invention, also comprise other additives, for example antioxidants or light protection agents.

Incorporation into the organic polymers, for example into the synthetic organic, in particular thermoplastic, polymers can take place by adding the halogenated diphenyl ether compound according to the invention and, if desired, other additives by the methods customary in the art. Incorporation can expediently take place before or during shaping, for example by mixing the pulverulent components or by adding the antimicrobial active substance to the melt or solution of the polymer, or by applying the dissolved or dispersed compounds to the polymer, if desired with subsequent evaporation of the solvent. Another method of incorporating the mixtures according to the invention into polymers involves adding the former before or during polymerization of the corresponding monomers or before crosslinking.

The mixtures according to the invention can also be added to the organic polymers to be finished in the form of a masterbatch which comprises these compounds, for example, in a concentration of from 2.5 to 25% by weight.

The resulting antimicrobially finished polymer compositions can be converted into shaped articles, for example fibres, films, tapes, sheets, multi-wall sheets, containers, tubes and other profiles, by conventional methods, for example by hot pressing, spinning, extrusion or injection moulding.

The diphenyl ether derivatives of the formula (1 ) are also suitable for the antimicrobial finishing of undyed and dyed or printed fibre materials made, for example, of silk, wool, polyamide or polyurethane, and in particular of cellulosic fibre materials of all types. Examples of such fibre materials are the natural cellulose fibres, such as cotton, linen, jute and hemp, and also pulp and regenerated cellulose. Preference is given to textile fibre materials made of cotton. The diphenyl ether derivatives according to the invention are also suitable for the antimicrobial finishing of hydroxyl-group-containing fibres which are present in mixed fabrics, for example, of mixtures of cotton with polyester fibres or polyamide fibres. For this purpose, one or more compounds of the formula (1) are advantageously applied to the textile fibre material in an amount of from 0.01 to 5% by weight, preferably 0.1-3% by weight, and in particular from 0.25 to 2% by weight, based on the weight of the fibre material, in a process analogous to dyeing.

The diphenyl ether derivatives according to the invention can be applied to the fibre material and fixed to the fibre in different ways, in particular in the form of aqueous dispersions or printing pastes.

The textile fibre materials finished using the compounds of the formula (1 ) according to the invention have an excellent and long-lasting antimicrobial protection.

The diphenyl ether derivatives according to the invention are also useful for the disinfection of the skin, mucous membrane and hair, preferably for the disinfection of hands and wounds.

Therefore, these compounds are suitable as an antimicrobial active substance in personal care products as shampoos, bath- and shower additives, hair-care products, liquid and bar soaps, lotions and cremes, deodorants, other aqueous or alcoholic solutions, for example cleaning solutions for the skin, moist cleaning sheets, oils and powders.

A further subject of the present invention is therefore a personal care composition comprising at least one compound of the formula (1) and cosmetically tolerable carriers or auxiliaries.

The personal care composition according to the present invention comprises 0.01 to 15, preferably 0.5 to 10 % b.w. of the diphenyl ether derivative of formula (1) and cosmetically tolerable carriers or auxiliaries.

The personal care composition according to the invention can be formulated as a water-in-oil or oil-in-water emulsion, as an oil-in-alcohol lotion, as a vesicular dispersion of an ionic or non-ionic amphiphilic lipid, as a gel, solid stick or as an aerosol formulation. As a water-in-oil or oil-in-water emulsion, the cosmetically compatible auxiliary preferably contains 5 to 50% of an oil phase, 5 to 20% of an emulsifier and 30 to 90% of water. The oil phase can in this case contain any oil suitable for cosmetic formulations, e.g. 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.

Furthermore the diphenyl ether derivatives according to the invention are useful as household cleaners for the cleaning and disinfection of hard surfaces.

The examples below serve to illustrate the invention.

Preparation Examples of novel compounds

Example 1 : Reaction equation:

9.0 g (14.5 mmol) of the compound of the formula (101a) are dissolved in 120 ml of methanol. 0.2 ml (1.08 mmol) of an approximately 30% NaOCH3 solution is then added, and the mixture is stirred at room temperature for 2 hours. After 30 minutes, the reaction is virtually complete. A yellow-red solution forms, which is evaporated to give 6.72 g of a beige- reddish substance, which corresponds to the compound of the formula (101), which is purified by column chromatography (column: CHCl3/MeOH 10:1). Yield: 5.87 g

Elemental analysis:

Calculated Found

C 47.86 % 47.4 %

H 3.79 % 3.8 %

CI 23.55 % 23.5 %

Example 2: Reaction equation:

(102a) (102)

14.5 g (50 mmol) of the compound of the formula (102a) are dissolved in 100 ml of a xylene isomer mixture and 3.96 g (50 mmol) of pyridine. The mixture is heated to 130°C, and

11.16 g (50 mmol) of lauroyl chloride, diluted with 20 ml of xylene isomer mixture, are added dropwise over the course of 20 minutes. The mixture is left to cool to room temperature,

150 ml of water are added and the pH is adjusted to slightly acidic using 2 n HCI. The organic phase is separated off using a separating funnel, washed with 1 x 150 ml of water, dried over Na₂SO₄ and evaporated to dryness.

This gives 23.5 g of crude product of the compound of the formula (102), which is distilled under a high vacuum.

Yield: 20.9 g; b.p.: 215-220°C/0.02 torr.

Example 3: Reaction equation:

72.4 g (25 mmol) of the compound of the formula (102a) are dissolved in 500 ml of methyl Cellosolve at 80°C. 26.5 g (25 mmol) of Na₂CO₃ are stirred into this solution at 80°C. The solution is then stirred for 30 minutes at from 80 to 85°C. 25.5 g (25 mmol) of epichlorohydrin, which is diluted with 25 ml of methyl Cellosolve, is then added dropwise with stirring over the course of 45 minutes at a temperature of from 80 to 85°C. The warm solution is then decanted and evaporated to dryness. The residue is dissolved in 300 ml of toluene, filtered and extracted by shaking twice with water, dried over Na₂SO₄ and evaporated to dryness. Yield:89.8q

Example 4: Reaction equation:

(104)

8.7 g (30 mmol) of the compound of the formula (102a) are introduced into 100 ml of xylene isomer mixture. 8.2 g (30 mmol) of the 1 :1 isomer mixture of the formulae

O O

/ \ / \

(104a) H₃C - (CH₂)₁₁ - O - CH₂ - CH - CH₂ and (104b) H₃C - (CH₂)₁₂ - O - CH₂ - CH - CH₂ , and 0.5 g of ethyltriphenylphosphonium bromide are added over the course of 8.5 hours at a temperature of from 130 to 140°C.

After the reaction has ended, the mixture is left to cool to 100°C and 100 ml of water are added, the mixture is thoroughly stirred, and the organic phase is separated off, dried over

Na₂SO₄ and evaporated to dryness.

Yield: 18.2 g of the 1 :1 mixture of the compound of the formula (104). Example 5: Reaction equation:

(105)

29.0 g (0.1 mol) of the compound of the formula (102a) and 9.2 g (0.05 mol) of cyanuric chloride are dissolved in 150 ml of toluene. At 0°C, 6.1 g of coliidine are added dropwise, as a result of which, the temperature increases to 10°C. The reaction is then completed by stirring the mixture for 12 hours at room temperature. After the reaction composition has been quenched with 500 ml of water, the organic phase is separated off, washed with 200 ml of water and dried over sodium sulfate. The solvent is stripped off to give the compound of the formula (105) as a viscous oil, which crystallizes at 0°C after some time.

Purity (HPLC, F%): 80%) Yield: 15.0 g

Example 6: Reaction equation:

(106)

24.9 g (0.1 mol) of the compound of the formula (107) and 9.2 g (0.05 mol) of cyanuric chloride are dissolved in 150 ml of toluene. At 0°C, 6.1 g of coliidine are added dropwise, as a result of which the temperature increases to 10°C. The reaction is then completed by a result of which the temperature increases to 10°C. The reaction is then completed by stirring the mixture for 12 hours at room temperature. After the reaction composition has been quenched with approximately 500 ml of water, the organic phase is separated off, washed with 200 ml of water and dried over sodium sulfate. The solvent is stripped off to give the compound of the formula (106) as a colourless oil which crystallizes slowly at 0°C.

Purity (HPLC, F%): 85% Yield: 14.5 g

Example 7: Reaction equation:

(107) (108)

62.3 g (0.25 mol) of the compound of the formula (107) are dissolved in 500 ml of methyl Cellosolve at 80°C. 26.5 g (0.25 mol) of Na2CO₃ are stirred into this solution at 80°C. The solution is then stirred for 30 minutes at from 80 to 85°C. 25.5 g (0.25 mol) of epichlorohydrin, which is diluted with 25 ml of methyl Cellosolve, is then added dropwise with stirring over the course of 45 minutes at a temperature of from 80 to 85°C. The warm solution is then decanted off from the insoluble matter and evaporated to dryness. The residue is taken up in 300 ml of toluene and the solution is filtered, extracted by shaking twice with water, dried over sodium sulfate and evaporated to dryness. Yield: 85.4g Application Examples:

Example 8: Determination of the antimicrobial activity of the compound of the formula

11321

Test method:

An agar well test is carried out (method CG 126) with the following modifications:

Medium: Casein soybean flour peptone agar (Caso-agar)

Test bacteria: Staphylococcus aureus ATCC 9144 Escherichia coli NCTC 8196

Procedure: 500ml of Caso-agar are inoculated with 3.5 ml of a 1 :100 diluted overnight culture of the bacteria, and plates with a volume of about 18 ml are poured.

After the plates have cooled, wells having a diameter of 1 cm are cut out using a cork borer (a maximum of 4 wells per plate). 100 μi of the compound of the formula (102) are poured into each well, and the plates are incubated at 37°C (E. coli and S. aureus for 24 hours). Dilutions of the compound of the formula (102) are prepared in 96% analytical grade ethanol.

Results:

The zones of inhibition are observed after incubation for 24 hours. The results in Table 1 show that the compound of the formula (102) has excellent antimicrobial activity. Example 9: Determination of the antimicrobial activity of the compound of the formula (103) An agar well test corresponding to method CG 126 is carried out with the following modifications:

Medium: Casein soybean flour peptone agar (Caso-agar)

Test bacteria: Staphylococcus aureus ATCC 9144 Escherichia coli NCTC 8196

Procedure: 500 ml of Caso-agar are inoculated with 3.5 ml of a 1 :100 diluted overnight culture of the bacteria, and Caso plates (18 ml) are coated with about 5 ml of the bacteria-containing agar.

After the plates have cooled, wells having a diameter of 1 cm are cut out using a cork borer (one well per plate; all test substance concentrations are tested twice).

100 μl of the compound of the formula (103) (in 96% ethanol) are poured into each well, and the plates are incubated at 37°C for about 24 hours.

The results are given in Table 2.

All dilutions are tested twice and both results are given in the table. The results show that the compound of the formula (103) has excellent bacteriostatic activity.

Example 10: Determination of the minimum inhibitory concentration (MIC) of the compound of the formula (101):

An agar incorporation test is carried out to determine the MIC:

Medium: Nutrient agar as test agar for bacteria:

Casein soybean flour peptone agar to cultivate the microorganisms 0.9% sodium chloride (pH 7.2) for obtaining the bacterium suspension Methyl Cellosolve as solvent

Test bacteria Escherichia coli NCTC 8196 Pseudomonas aeruginosa CIP A-22 Serratia marcescens ATCC 14756 Enterococcus faecium ATTC 10'541 Staphylococcus aureus ATCC 9144 Candida albicans ATCC 10'23q

Procedure: The test substances are dissolved in methyl Cellosolve, and a dilution series of the compound of the formula (101) in agar are prepared.

After the cultures have been cultivated on casein soybean flour peptone agar, the cells are floated out using NaCI solution and adjusted to a density of about 10⁶ CFU/ml (live bacterial count).

1 μl of each bacterial suspension is dropped onto the agar plates containing the test substance, and the plates are then incubated at 37°C for 2 days. As controls, the bacterial suspensions are applied to agar plates without test substances. In order to exclude the solvent methyl Cellosolve having an influence on the growth properties, the bacterial suspensions are applied to agar plates containing methyl Cellosolve, but without test substance. After the plates have been incubated, the growth of the bacteria on the test-substance-containing plates is compared with that on the control plates.

The minimum inhibitory concentration (MIC) is given as the lowest concentration which shows clear inhibition compared with the control.

The MIC values are given in the table below.

The results in Table 3 clearly show that the compound of the formula (101) has antimicrobial activity.

Preparation of formulations

Example 11 : Preparation of a liquid hand soap

Composition (100% active ingredients) % w/w A Compound of formula (102) 1% B Sodium Laureth-2 Sulfate 10.0%

Sodium Cumene sulfonate 3.0% C Hydroxypropylmethylcellulose 1.0% D Perfume / Dyestuff q.s. E Ethanolamine up to pH 5.5 F Deionized water to 100.0% Preparation procedure:

At room temperature, (C) is added by stirring to 50% of the calculated amount of the formulation. The suspension is heated up to about 60°C and stirred until (C) is dissolved completely.

Compounds of (B) are dissolved in 15% of the calculated amount of formulation by stirring and heating up to about 60°C until a clear solution is formed.

(A) is added to solution B, pH is adjusted with E to about 5.0. Solution (C) is added and after stirring the pH is adjusted to 5.5 with (E). F is added to 100%.

Example 12: Preparation of a liquid hand soap

Composition (100% active ingredients) % w/w

A Compound of formula (101 ) 1 %

B Sodium Laureth-2 Sulfate 10.0%

Sodium Cumene sulfonate 3.0%

C Hydroxypropylmethylcellulose 1.0%

D Perfume / Dyestuff q.s.

E Ethanolamine up to pH 5.5

F Deionized water to 100.0%

Preparation procedure

(A) is added to solution (B), pH is adjusted with (E) to about 5.0. Solution (C) is added and after stirring the pH is adjusted to 5.5 with (E). F is added to 100%.

Example 13: Preparation of a natural bar soap

Composition (100% active inqredients) % w/w

A Compound of formula (102) 0.5%

B Sodium tallowate 90.0%

Sodium cocoate

C Stearic acid 3.0%

D Titanium dioxide 0.3%

E Tetrasodium EDTA 0.03%

F Glycerine 3.0%

G Perfume q.s.

H Deion. water ad 100.0%

Example 14: Preparation of a natural bar soap

Composition (100% active inqredients) % w/w

A Compound of formula (101 ) 0.7%

B Sodium tallowate 93.0%

Sodium cocoate

C Titanium dioxide 0.3%

D Tetrasodium EDTA 0.03%

E Glycerine 3.0%

F Perfume q.s.

G Deion. water ad 100.0% Example 15: Preparation of a deodorant roll-on

Composition (100% active inqredients) % w/w

A Compound o formula (102) 0.3%

B Steareth-10 4.0%

C PPG-25 Laureth-25 5.0%

D Cetylalcohol 2.0%

E Mineral Oil 9.0%

F Propylene Glycol 4.0%

G Preservatives / Perfume / Dyestuff q.s.

H Deionized water to 100.0%

Preparation procedure for Examples 13-15:

1. (A) is dissolved in F. E and B are added and the mixture is stirred homogeneous.

(D) is added, the suspension is heated up to -70°C and stirred until D is melted.

2. (C) is added to the calculated amount of H, the solution is heated to ~70°C.

3. Solution (2) is added to (1) and stirred at maximum speed. Then slowly cool down under continuos stirring. G is added at ~40°C.

Example 16: Preparation of a Deodorant Roll-on

Composition (100% active ingredients) % w/w

A Compound of formula (101) 0.3%

B Steareth-10 4.0%

C PPG-25 Laureth-25 5.0%

D Cetylalcohol 2.0%

E Mineral Oil 9.0%

F Propylene Glycol 4.0%

G Preservatives / Perfume / Dyestuff q.s.

H Deionized water to 100.0% Preparation procedure:

1. (A) is dissolved in (F). (E) and (B) are added and the mixture is stirred homogeneous.

(D) is added, the suspension is heated up to ~70°C and stirred until (D) is melted.

3. Solution (2) is added to (1 ) and stirred at maximum speed. Then slowly cool down under continuos stirring. (G) is added at ~40°C.

Example 17: Preparation of a liguid laundry detergent

Composition (100% active ingredients) % w/w

A Compound of formula (105) 1%

B PEG-7 C14-15 alcohol ether 15%

Sodium Dodecylbenzenesulfonate 10.0%

Propylene Glycol 10.0%

C Deionized water to 100.0%

Preparation procedure:

Dissolve (A) in (B) and 25% of (C).

Add (C) up to 100%

Example 18: Preparation of a liguid laundry detergent

Composition (100% active inqredients) % w/w

A Compound of formula (106) 1 %

B PEG-7 C14-15 alcohol ether 15%

Sodium Dodecylbenzenesulfonate 10.0%

Propylene Glycol 10.0%

C Deionized water to 100.0%

Preparation procedure:

Dissolve (A) in (B) and 25% of (C).

Add (C) up to 100% Example 19: Preparation of a laundry detergent powder

Composition (100% active ingredients) % w/w

A Compound of formula (105) 0.3%

B Lauryl ammonium sulfate 8.0%

Non-ionic surfactants 2.9%

Soaps 3.5%

Sodium tripolyphosphate 43.8%

Sodium silicate 7.5%

Magnesium silicate 1.9%

Carboxymethylcellulose 1.2%

EDTA 0.2%

Sodium sulfate 21.2%

Water to 100%

Example 20: Preparation of a laundry detergent powder

Composition (100% active ingredients) % w/w

A Compound of formula (106) 0.3%

B Lauryl ammonium sulfate 8.0%

Non-ionic surfactants 2.9%

Soaps 3.5%

Sodium tripolyphosphate 43.8%

Sodium silicate 7.5%

Magnesium silicate 1.9%

Carboxymethylcellulose 1.2%

EDTA 0.2%

Sodium sulfate 21.2%

Water to 100% Example 21 : Preparation of a dish washing detergent

Composition (100% active ingredients) % w/w

A Compound of formula (102) 0.5%

B Sodium lauryl sulfate 7.0%

C Sodium myrethsulfate 7.0%

D Lauryl glucoside 4.0%

E Coco betaine 1.1%

F Ethanol 5.0%

G Citric acid 1.0%

H Water to 100%

Preparation procedure of Examples 19-21 :

1. (B), (C), (D) and (E) are dissolved in part of H at 40°C.

2. (A) is added and stirred at 40°C.

3. (F) and (G) and the rest of (H) is added at 22°C. 4.pH is adjusted to 5.

Example 22: 10 grams of the compound of formula (102) is added into 45 grams of low density polyethylene (Escorene LL6301 XR, from Exxon) and 45 grams of low density polyethylene (Escorene LL6301 RQ, from Exxon). The mixture is tumble mixed for 10 minutes followed by addition into a 29mm twin-extruder to produce a master batch. The extrusion temperature is set at 180°C.

Example 23: 10 gram of the resulting master batch (contains 10% of compound of formula 102) in Example 22 is added into 90 grams of low density polyethylene pellets (Escorene LL6301 XR, from Exxon) and well mixed. The mixture is then charged into an injection moulding machine to produce low density polyethylene plates (10 x 20 cm, thickness 2mm). The resulting low density polyethylene plates contain 1% of compound of formula (102). The plates are then cut into discs of 2 cm in diameter and tested for antimicrobial efficacy in agar diffusion test by using the same procedures as described in Example 8.

The results are listed in Table 4.

The test results show that the compound of formula (102) shows a good antimicrobial efficacy.

Claims

WHAT IS CLAIMED IS:

1. An O-derivative of a halogenated diphenyl ether compound of the formula

, in which

R₁ and R₂ independently of one another are F, CI or Br;

Y is a radical of the formula ;

0┬░) , -(CH₂,)

R₃ is C^C^alkyl; C^C^alkoxy; phenyl; phenyl-C^C^Ikyl; ΓÇö (CH₂)_p - A⁺R₅R₆R₇ ;

4

the radical of the formula

R₄ C₁-C₂₂alkyl;

R₅, R₆, R₇ and R₈ independently of one another are hydrogen; C₁-C₄all yl; sulfo- C.-C₄alkyl; or R₅ and R₆ together with A form a cyclic radical unsubstituted or substituted by sulfo groups; or R₇ and R₈ together with N form a cyclic radical unsubstituted or substituted by sulfo groups;

A is N or P; Z, is fluorine, chlorine, the radical of the formula (1g) or Z?

Z₂ is fluorine, chlorine, C_rC₂₂alkoxy, CrC^alkylthio or C╬╣-C₂₂-monoalkylamino or C C₂₂dialkylamino; each of which is unsubstituted or substituted by OH, NH₂ or sulfo; C₆- C₁₂aryloxy, C₆-C₁₂arylthio or C₆-C₁₂monoarylamino or C₆-C╬╣₂diarylamino, each of which is unsubstituted or substituted by OH, NH₂ or sulfo; m is from 1 to 3; n is 1 or 2; and p_v p₂, p_3> p₄ and p₅ independently of one another are 1-4.

2. A compound according to claim 1 of the formula

in which

R R₂, R₃, m and n are as defined in claim 1.

3. A compound according to claim 2 wherein, in formula (2), R₃ is C-|-Ci2alkyl; or phenyl.

4. A compound according to claim 2 or 3, wherein R, and R₂ are chlorine;

R₃ is C C₁₂alkyl; m is 2; and n is 1.

5. A compound according to claim 1 of the formula

in which

R_v R₂, R₄, m, n, p₁ and p22 are as defined in claim 1.

6. A compound according to claim 1 of the formula

in which

R_1f R₂, n, m and p₂ are as defined in claim 1.

7. A compound according to claim 1 of the formula

in which

V is a radical of the formula (1 g).

8. A process for the preparation of the compound of the formula (1 ), in which

Y is a radical of the formula (1 b);

R₃ is O_j-C^alkyl; C^C^alkoxy; phenyl; phenyl-C₁-C4alkyl; and

R R₂, m and n are as defined in claim 1 , by esterification of the phenolic OH group of the compound of the formula

with an acyl halide compound.

9. A process for the preparation of the compounds of the formula (1 ), in which Y is a radical of the formula (1 a) or (1 c); and

R R₂, m and n are as defined in claim 1 , by etherification of the phenolic OH group of the compound of the formula

with the corresponding halide compound.

10. A process for the antimicrobial finishing of organic material, which comprises adding at least one compound of the formula (1 ) thereto.

11. The use of the compounds according to any one of claims 1 to 7 for the antimicrobial finishing of polymeric materials.

12. A composition comprising

(A) an organic material to be antimicrobially finished and

(B) as antimicrobial active substance, at least one compound according to any one of claims 1 to 5.

13. The use of the compounds according to any one of claims 1 to 7 for finishing of undyed and dyed or printed fibre materials.

14. The use of the compounds according to any one of claims 1 to 7 for the disinfection of the skin, mucous membrane and hair in personal care products.

15. A personal care composition comprising at least one compound of the formula (1) and cosmetically tolerable carriers or auxiliaries.