DE2004302A1 - New O, N-diphenyl-carbamic acid esters, processes for their preparation and their use for combating microorganisms - Google Patents

Description

The present invention relates to new O, N-diphenylcarbamic acid esters, processes for the preparation of these compounds and agents and methods for combating microorganisms using the new carbamic acid esters.

The new O, N-diphenyl-carbamic acid esters (carbanilic acid phenyl esters) correspond to the formula I.

In this formula: R [deep] 1 is a phenoxy radical substituted by at least one and at most 3 identical or different halogen atoms, of the symbols R [deep] 2, R [deep] 3 and R [deep] 4 at least one chlorine or bromine, the others independently hydrogen, chlorine or bromine, R [deep] 5 and R [deep] 7 independently hydrogen, halogen, lower alkyl, lower alkoxy, lower haloalkyl, nitro and hydroxyl, R [deep] 6 hydrogen, halogen, lower Alkyl, lower alkoxy, dialkylamino, hydroxyl, and X is oxygen or sulfur.

In formula I, R [deep] 1 represents in particular one of the following halogenated phenoxy radicals: 4-chlorophenoxy, 4-bromophenoxy, 2,4-dichlorophenoxy, 2,4-dibromophenoxy, 2,4,5-trichlorophenoxy.

Lower alkyl and lower alkoxy as radicals R [deep] 5 to R [deep] 7 have 1 to 4 carbon atoms. Trifluoromethyl is preferred as the haloalkyl. The alkyl substituents in a dialkylamino group are radicals with 1 to 4 carbon atoms, especially methyl radicals. Halogen, which is represented by R [deep] 5, R [deep] 6 and / or R [deep] 7, is to be understood as meaning fluorine, chlorine, bromine and iodine, but in particular fluorine, chlorine and / or bromine.

The new O, N-diphenyl-carbamic acid esters are obtained according to the invention by adding a phenol of the formula II as such or in the form of one of its alkali or alkaline earth metal salts either a) with phosgene or thiophosgene in an acid chloride of the formula III transferred and this with an aniline of the formula IV reacts, or b) in those cases in which X is oxygen, with a phenyl isocyanate of the formula V implements. In the formulas I to V, the symbols R [deep] 1 to R [deep] 7 and X have the meanings given under formula I.

The process according to the invention is preferably carried out in the presence of a solvent or diluent and an acid-binding agent (proton acceptor).

Examples of suitable solvents or diluents are: hydrocarbons such as toluene, benzene or ligroin, halogenated hydrocarbons such as chloroform, carbon tetrachloride or chlorobenzene, amides such as dimethylformamide, ethers and ethereal compounds such as tetrahydrofuran, dioxane or diisopropyl ether, ketones such as acetone or methyl ethyl ketone.

Acid-binding agents are preferably organic bases, e.g. tertiary amines such as pyridine, triethylamine, etc., inorganic bases such as the hydroxides and carbonates of alkali and alkaline earth metals.

The preparation of some diphenylcarbamic acid esters of the formula I is described in the following examples. The temperatures are given in degrees Celsius.

Example 1 a) Approx. 100 g of phosgene are passed into 500 ml of toluene at 0 °. A solution of 289.5 g of 4,2 ', 4'-trichloro-2-hydroxydiphenyl ether in 700 ml of toluene is added dropwise to this solution at 0 ° to 5 °, and a further 100 g of phosgene are introduced. A solution of 111.3 g of triethylamine in 200 ml of toluene is then added to the reaction mixture with stirring. After standing for several hours at room temperature, excess phosgene is removed, the triethylamine hydrochloride separated off and the solvent of the filtrate was distilled off. The residue is fractionated, the O- [2- (2 ', 4'-dichlorophenoxy) -5-chlorophenyl] carbonic acid chloride boils at 180-184 ° and 0.5 Torr.

b) 35.2 g of O- [2- (2 ', 4'-dichlorophenoxy) -5-chlorophenyl] carbonic acid chloride, dissolved in 300 ml of acetone are added dropwise at 15 to 20 ° with a solution of 32.4 g of 3, 5-dichloroaniline was added to 150 ml of acetone.

The reaction mixture is then left to stand for 3 hours at room temperature, it is poured into water and the precipitate which separates out after a few hours is filtered off. After repeated recrystallization from cyclohexane and benzene / petroleum ether, the N- (3,5-dichlorophenyl) -carbamic acid-O- [2- (2 ', 4'-dichlorophenoxy) -5-chlorophenyl] ester is obtained with the melting point: 132-134 °.

Example 2 a) A solution of 150 g of thiophosgene in 400 ml of chloroform is added to a solution of 289.5 g of 2 ', 4'-dichloro-2-hydroxy-4-chloro-diphenyl ether in 400 ml of chloroform and the mixture is cooled to 5 ° C from. An aqueous sodium hydroxide solution, 50 g of sodium hydroxide dissolved in 790 ml of water, is then added dropwise with vigorous stirring so that the temperature does not exceed 15 °. The reaction mixture is then stirred for 2 hours at room temperature and dried over sodium sulfate. After the solvent has been distilled off, the residue is fractionated in vacuo. The 2- (2 ', 4'-dichlorophenoxy) -5-chlorophenyl-thiocarbonic acid chloride boils at 175-184 ° 0.05 Torr. (n [low] D [high] 20 = 1.6275).

b) A solution of 24.2 g of 3,5-dimethylaniline in 150 ml of benzene is added to a solution of 36 g of O- [2, (2 ', 4'-dichlorophenoxy) -5-chlorophenyl] thiocarbonic acid chloride in 150 ml of benzene added dropwise at 5 ° C within 1.5 hours. The mixture is then stirred for 12 hours at room temperature, extracted with water and dried over sodium sulfate. After the solvent has been distilled off, the remaining O- [2- (2 ', 4'-dichlorophenoxy) -5-chlorophenyl] -thiocarbamic acid N- (3,5-dimethylphenyl) ester has recrystallized from benzene / petroleum ether, the melting point .: 102-104 °.

Example 3 A solution of 19.8 g of 3-bromo-phenyl isocyanate in 50 ml of ligroin is added dropwise to a suspension of 30 g of 4'-bromo-4-chloro-2-hydroxy-diphenyl ether in 100 ml of ligroin. After adding 2 ml of triethylamine, the mixture is refluxed for one hour and then cooled. The deposited precipitate is separated off and recrystallized from benzene / petroleum ether (1: 1).

The N- (3-bromophenyl) -carbamic acid-O- [2- (4-bromophenoxy) -5-chlorophenyl] -ester has the melting point: 116 °.

In a manner analogous to the preceding examples, the following O, N-diphenylcarbamic acid esters of the formula I are prepared.

Table 1

Table 1 continued Table 1 continued Table 1 continued

The new carbamic acid esters of the formula I are colorless solid bodies which can be purified by recrystallization. In addition to their colorlessness or low inherent color, they are also characterized by low toxicity for warm-blooded animals; in addition, the concentrations in question for the skin are non-irritating. This colorlessness opens up many areas of application for them, which are closed to strongly colored connections.

The new diphenyl-carbamic acid esters of the formula I show very good bacteriostatic and bactericidal properties against gram-positive and gram-negative bacteria, for example: Staphylococcus aureus SG 511, Staphylococcus aureus Smith, Staphylococcus lactis, and also Bacillus mesentericus, Bacillus pumilus, diptheria colory, Bacnebiforme bacteria Clostridium botulinum, Clostridium butyricum, Clostridium welchii, Clostridium tetani, Klebsiella pneumoniae, Alcaligenes faecalis, Sarcina spec., Salmonella pullorum. Salmonella typhi, Salmonella paratyphi A and B, Salmonella typhimurium, Salmonella enteritidis, Shigella dysenteriae, Shigella flexneri, Brucella absortus, Proteus mirabilis, Achromobacter spec., Serratia marcescens, Pasteurella pseudotuberculosis. The compounds of the formula I also show very good fungistatic and fungicidal properties, for example against the following fungi: Aspergillus spec. e.g. Aspergillus niger, Aspergillus flavus, Aspergillus funigatus, Candida spec. for example Candida albicans, Candida tropicalis, Penicillium spec., for example Penicillium italicum, Penicillium chrysogenum, Epidermophyton spec., Trichophyton spec., Ctenomyces spec., Keratinomyces spec., Blastomyces spec., Microsporum spec., Cryptococcus neoformans var ., Alternaria tenuis, Acrostalagmus cinnabarinus, Fusarium oxysporum. Cellulose-degrading fungi, wood fungi, etc. The Dutch Auslegeschrift No. 6 606 753 includes, but does not describe, O-phenoxyphenyl-N-trifluoromethylphenyl-carbamic acid esters unsubstituted in the phenoxy group as anthelmintics. However, these compounds have no or only very weak microbicidal properties. Furthermore, a number of O-halophenyl-N-phenyl and O-phenyl-N-halophenyl-carbamic acid esters are available as herbicides as well as for the

Application in crop protection described. However, owing to their lack of action or the lack of breadth of action, these compounds are particularly unsuitable for combating pathogenic microorganisms, for example the urinary and intestinal systems in warm-blooded animals.

The following microorganisms were used to determine the bacteriostatic and fungistatic activity of the compounds of the formula I:

A. Bacteria: Escherichia coli, Bacillus pumilus, Sarcina ureae, Bacillus subtilis, Sarcina lutea, Streptococcus faecalis, Staph. saproph., staph. aureus, Corynebact. diphtheroides 17, Brevibakt. ammoniagenes, Salmonella pulloyrum, Proteus vulgaris HXL, Proteus vulgaris ox 19, Proteus mirabilis.

B. Fungi 1a Aspergillus niger, Penicillium italicum, Fuarium oxysporum, Candida albicans, Stemphylium botryosum,

1b Cellulose degradation: Chaetomium globosum, Trichoderma viride, Metarrhizium glutinosum, Stachybotrys atra,

2 yeast: Saccaromyces cerevisiae, Torula utilis, Monilia nigra,

3 opt. Dermatophytes: Trichophyton gypseum, Ctenomyces spec., Keratinomyces Ajelloi, Epidermophyton floccosum,

4 ubiquit. Saprophytes: Rhizopus nigricans, Paecilomyces varioti, Penicillium citrinum, Aspergillus oryzae, Aspergillus clavatus, Aspergillus flavus,

5 Fungi imperfecti: Scopulariopsis brevicaulis, Alternaria tenuis, Acrostalagmus cinnabarinus,

6 House rot: Cionophora cerebella, Poria vaporaria, Poria incarnata,

7 Storage rot: Polystictus versicolor, Daedalea quericina, Lenzites abietina, Lentinus lepideus,

8 parasites: Fomes annosus,

9 Wood stainers: Scopularia phycomyces, Pullularia pullulans.

C. Method To determine the limit concentration that inhibits the growth of the various microorganisms, the active ingredient solution is mixed with the still hot nutrient agar. The agar is then poured into plates and, after solidification, the test germs are spread on.

The following list contains: the nutrient media used for the various organisms, the incubation temperature and time as well as the active ingredient concentrations used:

Table 2 below shows the bacteriostatic activity and Table 3 shows the fungistatic activity of some of the compounds listed in Table 1 on some of the microorganisms listed above.

Table 2

Table 2 continued

Table 3

Table 3 continued

The bacteriostatic and funigstatic effect of active ingredients according to the invention was also determined by the following comparative tests, for which the method specified under C) was used:

The following microorganisms were used:

Attempt 1

A. Bacteria: Escherichia coli, Bacillus pumilus, Sarcina ureae, Staphyliococcus aureus, Proteus vulgaris HXL,

B. Fungi: 1 Aspergillus niger, Fusarium oxysporum, Candida albicans

2 yeasts: Saccaromyces cerevisiae, Torula utilis.

Attempt 2

Bacteria: Escherichia coli, Salmonella pullorum, Proteus vulgaris HXL.

The following list shows the nutrient media used for the various organisms, the incubation temperature and time as well as the active ingredient concentrations used:

The following compounds were used as comparison substances:

A) N- (3-trifluoromethylphenyl) carbamic acid O- (2-phenoxyphenyl) ester (known from French Patent No. 1,493,102) B) N- (3,5-bis-trifluoromethylphenyl) carbamine O- (2-phenoxyphenyl) acid ester (known from French Patent No. 1 493 102) C) O- (2-phenoxyphenyl) N- (3-trifluoromethylphenyl) thiocarbamic acid ester ( known from French Patent No. 1 493 102) D) N- (3-trifluoromethyl-6-chlorophenyl) thiocarbamic acid O- (2-phenoxyphenyl) ester (known from French Patent No. 1 493 102) E) Mixture of 2,6-toluene and 2,4-bis (pentachlorophenyl) carbamate (Swiss patent 436 207) F) Hexamethylene di (pentachlorophenyl) carbamate (Swiss patent 436 207) G. ) 3,4-dichlorophenyl-3,4-dichlorocarbanilate (US Patent 3,142,646)

In the following table 4 the values of experiment 1 and in table 5 those of experiment 2 for the microorganisms listed above are given. (The numerical values mean those concentrations at which growth can no longer be determined.)

Table 4

Table 5

The bactericidal effect was determined by means of the following tests:

A) Determination of the number of germs in the rinsing liquor The third rinsing bath containing the active ingredients was infected by means of Staphylococcus aureus SG 511 and Escherichia coli germs. 1 ml of this bath was added to 20 ml of nutrient agar [MacConkey, Difco
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9th edition (1953), page 131] or nutrient agar and potassium tellurite were added and the whole was poured into Petri dishes. The Petri dishes were incubated at 37 ° C. for 24 hours. The number of viable bacteria per ml of wash liquor was determined by counting the colonies that formed on the agar plates.

The substrate used was: for Staphilococcus aureus SG 511 nutrient agar + potassium tellurite, and for Escherichia coli nutrient agar.

The results are summarized in Table 6:

Table 6

B) Determination of the disinfecting effect on cotton material 20 ml nutrient agar or nutrient agar and potassium tellurite, which according to MacConkey [cf. A) above] has been prepared. A cotton rondelle rinsed with sterile Permutit water, which had been punched out of a cotton fabric rinsed in a rinsing bath inoculated with Staphylococcus aureus SG 511 and Escherichia coli, was placed on each of the agar plates. The Petri dishes prepared in this way were then incubated at 37 ° C. for 24 hours. The growth of the

Microorganisms on the agar plate were then determined visually. The results are given in Table 7, wherein

+ = Growth under the tissue - = no growth under the tissue +/- = traces of growth under the tissue

mean.

Table 7

C) Determination of the remanent effect on cotton material Two-layer agar plates were used to determine the remanent effect. These consist of a layer of Bacto agar (Difco No. B 140) and an agar layer inoculated with 24-hour-old test organisms. One was placed on each of the agar plates dried cotton discs prepared as described under B) are placed, and the agar plates prepared in this way are incubated at 37 ° C. for 24 hours. After this time, the extent of the inhibition zone created around the discs was measured in mm. The results are given in Table 8, in which the plus or minus sign indicates whether or not microorganism growth has taken place under the discs.

Table 8

The diphenylcarbamic acid esters of the formula I which can be prepared according to the invention can be used for combating microorganisms, in particular bacteria and fungi, and for protecting organic materials and objects from attack by microorganisms. So you can work them directly into the material to be protected, for example in synthetic resin-based material, such as polyamides and polyvinyl chloride, in paper treatment liquors, in printing thickeners made from starch or cellulose derivatives, in varnishes and paints containing, for example, casein, in cellulose, in viscose spinning pulp, in paper, in animal slimes or oils, in permanent sizes based on polyvinyl alcohol, in cosmetic articles, in ointments or powders. They can also be added to preparations of inorganic or organic pigments for the painting trade, plasticizers, etc. The new compounds are particularly valuable for protecting textiles of all kinds, e.g. textiles based on cellulose and material containing keratin, as they have a pronounced substantivity to such fiber materials.

The carbamic acid esters of the formula I can then be used in the form of their organic solutions, for example as so-called "sprays" or as dry cleaners or for impregnating wood, the organic solvents preferably being water-immiscible solvents, in particular petroleum fractions, but also water-miscible solvents , such as lower alcohols, for example methanol or ethanol or ethylene glycol monomethyl ether or monoethyl ether come into question.

They can also be used, together with wetting agents or dispersants, in the form of their aqueous dispersions, for example to protect substances that tend to rot, such as protecting leather, paper, etc.

Active ingredient solutions or dispersions which can be used to protect these materials advantageously have an active ingredient content of at least 0.005 g / liter.

A preferred field of application of the diphenylcarbamic acid esters of the formula I consists in the sterilization of laundry items and for protecting laundry items against attack by microorganisms. For this purpose, rinsing liquors are used which advantageously contain the carbamic acid esters mentioned in concentrations of approx. 5-200 parts per million, based on the liquor.

In addition, the liquor can also contain customary auxiliaries such as optical brighteners, plasticizers, acidic salts such as ammonium or zinc silicofluoride or certain organic acids such as oxalic acid, and also finishing agents, for example those based on synthetic resin or starch.

As laundry items that can be sterilized with rinsing liquors containing compounds according to the invention, organic fiber material comes into consideration, namely those of natural origin, such as cellulose-containing, for example cotton, or polypeptide-containing, for example wool or silk, or fiber material of synthetic origin, such as those on polyamide -, polyacrylonitrile or polyester base or mixtures of the above fibers.

The carbamic acid esters according to the invention in the above-mentioned concentrations give both the liquor and the laundry treated with it a largely and remanent sterility against Staphylococcus and coliforms, which remains even after exposure of the active ingredient or the goods treated with it. They are distinguished by their light resistance on the laundry treated with them and by their high activity and range of effects against gram-positive and gram-negative organisms.

The new carbamic acid esters are also very effective against the bacterial flora which produces a sweat odor and, because of their low toxicity, are suitable as deodorizing agents for laundry or as additives for cosmetic agents, such as ointments or creams.

Particularly valuable is the usability of the novel carbamic acid esters of the formula I that can be prepared according to the invention as active ingredients for curing disease states of the skin, the intestinal system and the urinary tract of warm-blooded animals, which result from the excellent effectiveness against pathogenic bacteria and fungi, the relatively low toxicity and the largely in unchanged, effective form results in excretion from the body.

The antimicrobial agents according to the invention contain at least one diphenylcarbamic acid ester of the formula I as an active ingredient together with customary pharmaceutical carriers. The type of carrier depends largely on the area of application. For external use, for example for disinfecting healthy skin such as for wound disinfection and for the treatment of dermatoses and mucosal affections caused by bacteria or fungi, ointments, powders and tinctures in particular come into consideration. The bases for ointments can be anhydrous, for example made up of mixtures of wool fat and vaseline, or they can be aqueous emulsions in which the active ingredient is suspended. Suitable carriers for powder are, for example, starches, such as rice starch, which, if desired, can be made specifically lighter by adding highly dispersed silica, or made heavier by adding talc.

Tinctures contain at least one diphenylcarbamic acid ester of the formula I in aqueous, in particular 45-75% ethanol, to which 10-20% glycerol may be added. In particular for disinfecting healthy skin, solutions that are prepared with the help of customary solubilizers, such as, for example, polyethylene glycol, and optionally emulsifiers, are also suitable. The active ingredient content of the aforementioned external use forms is preferably between 0.1 and 5%.

For mouth and throat disinfection, gargle water or concentrates for their preparation are suitable on the one hand, in particular alcoholic solutions with approx. 1-5% active ingredient content, to which glycerine and / or flavorings can be added, and on the other hand lozenges, ie solid dosage unit forms with a relatively high Content of sugar or similar substances and a relatively low active ingredient content of approx. 0.2-20%, as well as the usual additives such as binders and flavorings.

For intestinal disinfection and for the oral treatment of infections of the urinary tract, in particular solid dosage unit forms, such as tablets, dragees and capsules, which preferably contain between 10% and 90% of a diphenylcarbamic acid ester of form I, in order to facilitate the administration of daily doses between 0.1 and 2.5 g to adult humans or from appropriately reduced doses to children.

To produce tablets and dragee cores, the carbamic acid esters of the formula I are combined with solid, powdery carriers such as lactose, sucrose, sorbitol, corn starch, potato starch or amylopectin, cellulose derivatives or gelatin, preferably with the addition of lubricants such as magnesium or calcium stearate or Polyethylene glycols of suitable molecular weight. Dragee cores are then coated, for example, with concentrated sugar solutions, which may also contain gum arabic, talc and / or titanium dioxide, or with a varnish dissolved in volatile organic solvents or solvent mixtures. Dyes can be added to these coatings, for example to indicate different doses of active ingredients. Pearls (pearl-shaped closed capsules) and other closed capsules consist, for example, of a mixture of gelatin and glycerine and contain, for example, mixtures of a new carbamic acid ester of the formula I with polyethylene glycol. Push-fit capsules contain, for example, granules of an active ingredient with solid, powdery carriers, such as lactose, sucrose, sorbitol, mannitol, starches such as potato starch, corn starch or amylopectin, cellulose derivatives or gelatin, and magnesium stearate or stearic acid.

In all application forms, be they for technical, cosmetic, hygienic or medical fields of application, the new diphenylcarbamic acid esters of the formula I can be present as the sole active ingredients or can be combined with other known antimicrobial, in particular antibacterial and / or antimycotic active ingredients, for example for broadening of the area of action. You can, for example, with halogenated salicylic acid alkylamides and anilides, with halogenated diphenylureas, with halogenated benzoxazoles or benzoxazolones, with polychlorohydroxydiphenylmethanes, with halodihydroxydiphenylsulfides, with bactericidal 2-imino-imidazolidines or with certain bactericidal acidic compounds, such as quydrophederivyrimidazolidines or with quydropha-derivyrimidic acid or tetrahydrophenic acid carbamines, such as quydropha-derivyrimidazolidines or compounds with tetramethyl thiuram disulfide. If necessary, carrier substances with pharmacologically beneficial inherent effects, such as sulfur as a powder base or zinc stearate as a component of ointment bases, can also be used.

The following examples describe some typical forms of application for various areas of application,

Example 4 Wound powder: 3.00 g of active ingredient are thoroughly mixed with 5.0 g of zinc oxide, 41.9 g of rice starch and 50.0 g of talc, which in turn is impregnated with 0.1 g of perfume, and sieved through a suitable, fine sieve and mixed well again.

Example 5 Wound ointment: 3.0 g of active ingredient are rubbed with 3.0 g of paraffin oil and added to the mixture of 10.0 g of wool fat and 84.0 g of white vaseline, which is melted at a moderate temperature, and the mixture is allowed to cool while stirring.

Example 6 Lozenges for mouth and throat disinfection: 50.0 g of active ingredient are carefully mixed with 400.0 g of powdered sugar and evenly moistened with a granulating solution of 8.0 g of gelatin and 2.0 g of glycerol in about 120 g of water.

The mass is granulated through a suitable sieve and dried. A sieved mixture of 3.0 g of highly dispersed silica, 4.0 g of magnesium stearate, 0.7 g of flavorings and 42.3 g of talc is added to the dry granulate, mixed thoroughly and the mixture is compressed into 1000 tablets.

Example 7 Concentrate for gargle water: 5.0 g of active ingredient are dissolved in 60.0 g of 96% ethanol, 15.0 g of glycerol and 0.3 g of aromatic substances are added and the solution is mixed with 19.7 g of distilled water. Water supplemented to 100.0 g. Use about 5-20 drops of this concentrate in water for gargling.

Example 8 Tablets for intestinal and urinary tract disinfection: To prepare 1000 tablets each containing 150 mg of active ingredient, 150.0 g of active ingredient are first thoroughly mixed with 60.0 g of corn starch and 35.0 g of lactose and with one of 5.0 g of gelatin and 3.0 g glycerine evenly moistened in approx. 70 g of prepared granulating solution. The mass is granulated through a suitable sieve and dried. The granules are thoroughly mixed with a sieved mixture of 15.0 g talc, 10.0 g dried corn starch and 2.0 g magnesium stearate and the mixture is compressed into 1000 tablets.

Example 9 Dragees for disinfecting the intestines and urinary tract: To prepare 1000 dragees, 150.0 g of active ingredient are first thoroughly mixed with 60.0 g of corn starch and 34.0 g of lactose, the whole thing with a paste of 6.0 g of starch, 3.0 g glycerine and approx. 54 g dist. Mixed water, the resulting mass granulated through a suitable sieve and dried. The granulate is thoroughly mixed with a sieved mixture of 15.0 g talc, 10.0 g corn starch and 2.0 g magnesium stearate and the mixture is pressed into 1000 dragee cores of 280 mg each.

The above cores are coated in a coating pan with a layer composed as follows: Lacca 2.000 g, gum arabic 7.500 g, color 0.180 g, highly disperse silica 2.000 g, talc 35.000 g, sugar 58.320 g. 1000 dragees of 385 mg each and 150 mg of active ingredient each are obtained.

Claims (10)

1. New O, N-diphenyl-carbamic acid esters of the formula I: in which R [deep] 1 is a phenoxy radical substituted by at least one and at most 3 identical or different halogen atoms, of the symbols R [deep] 2, R [deep] 3 and R [deep] 4 at least one chlorine or bromine, the others independently of each other hydrogen, chlorine or bromine, R [deep] 5 and R [deep] 7 independently of one another hydrogen, halogen, lower alkyl, lower alkoxy, lower haloalkyl, nitro or hydroxyl, R [deep] 6 hydrogen, halogen, lower alkyl, lower Alkoxy, dialkylamino, hydroxyl and X is oxygen or sulfur. 2. N- (3,4-dichlorophenyl) carbamic acid O- [2- (2 ', 4'-dichlorophenoxy) -5-chlorophenyl] ester. 3. N- (3,5-Dimethylphenyl) carbamic acid O- [2- (2 ', 4'-dichlorophenoxy) -5-chlorophenyl] ester. 4. N- (3-methylphenyl) thiocarbamic acid O- [2- (2 ', 4' dichlorophenoxy) -5-chlorophenyl] ester. 5. Process for the preparation of O, N-diphenyl-carbamic acid esters of the formula I of claim 1, characterized in that a phenol of the formula II as such or in the form of one of its alkali or alkaline earth metal salts either a) with phosgene or thiophosgene in an acid chloride of the formula III transferred and this with an aniline of the formula IV reacts, or b) in those cases in which X is oxygen, with an isocyanate of the formula V implements. 6. Agents for combating microorganisms and for protecting organic materials and articles of daily use from attack by microorganisms, characterized in that they contain an O, N-diphenylcarbamic acid ester of the formula I. in which R [deep] 1 is a phenoxy radical substituted by at least one and at most 3 identical or different halogen atoms, of the symbols R [deep] 2, R [deep] 3 and R [deep] 4 at least one chlorine or bromine, the others independently of each other hydrogen, chlorine or bromine, R [deep] 5 and R [deep] 7 independently of one another hydrogen, halogen, lower alkyl, lower alkoxy, lower haloalkyl, nitro or hydroxyl, R [deep] 6 hydrogen, halogen, lower alkyl, lower Alkoxy, dialkylamino, hydroxyl and X is oxygen or sulfur, in combination with suitable carriers and / or distribution agents. 7. Agent according to claim 6, characterized in that the O, N-diphenyl-carbamic acid ester of the formula I is N- (3,4-dichlorophenyl) -carbamic acid-O- [2- (2 ', 4' -dichlorophenoxy) -5 chlorophenyl] ester is used. 8. Composition according to claim 6, characterized in that the O, N-diphenyl-carbamic acid ester of the formula I, N- (3,5-dimethylphenyl) -carbamic acid-O- [2- (2 ', 4'-dichlorophenoxy) - 5-chlorophenyl] ester is used. 9. Agent according to claim 6, characterized in that the O, N-diphenyl-carbamic acid ester of the formula I is N- (3-methylphenyl) -carbamic acid-O- [2- (2 ', 4'-dichlorophenoxy) -5-chlorophenyl ] ester is used. 10. A method for combating microorganisms and for protecting organic materials and articles of daily use from attack by microorganisms, characterized by the use of O, N-diphenlycarbamic acid esters of the formula I of claim 1 or of agents according to claim 5.