NL8500548A - NITRODIARYL SULFOXIDE DERIVATIVES, METHOD FOR PREPARING THE SAME, AND PHARMACEUTICAL AND PESTICIDE PREPARATIONS WITH SUCH COMPOUNDS IN IT AS AN ACTIVE SUBSTANCE. - Google Patents

Description

NL 32681-Kp / cs

Nitrodiarylsulfoxide derivatives, process for their preparation as well as pharmaceutical and pesticidal preparations containing such compounds as active ingredient.

The invention relates to new nitrodiarylsulfoxide derivatives, to a process for their preparation, and to pharmaceutical and pesticidal preparations containing such derivatives as the active ingredient. More particularly, the invention relates to novel nitrodiaryl sulfoxide derivatives of formula 1 of the formula sheet, wherein R is halogen or alkoxy of 1-6 carbon atoms, 2 R hydrogen, halogen, alkyl of 1-6 carbon atoms, alkoxy with 1-6 carbon atoms, or phenyl or phenylthio, optionally substituted by one or more equal or different halogen (halogens) and / or nitro group (s).

According to another aspect of the invention, it is a matter of providing a process for the preparation of new compounds of formula 1 of the formula sheet, wherein 1 2 R and R have the above meanings, by reduction of an arylsulfonyl halide of formula 2 of the formula-1 sheet, wherein R has the above meaning, and 1 is 20 X halogen, with an alkali metal sulfite, after which the aryl sulfinate of formula 3 of the formula sheet obtained, wherein 1 R has the above meaning, and M is an alkali metal, 25 is treated with an acid, followed by treatment of the obtained arylsulfinic acid of formula 4 of the formula I sheet, wherein R has the above meaning, or the aryl sulfinate of formula 3 of the formula sheet, wherein R and M have the above meanings, with a halogenating agent, followed by reaction of the obtained new arylsulfinyl halide of formula 5 of the formula sheet, wherein R is the above-mentioned s has and X is halogen, with a benzene derivative of formula 6 of the formula sheet, wherein R has the meaning defined in formula 1 8500548-1-2 - in the presence of a Lewis acid type metal halide catalyst.

The new compounds of formula 1 of the formula sheet are pharmaceutically active and can be used in particular in veterinary therapy, for example as nematocides, taenicides, etc., and preferably as anthelmintics, and subsequently have pesticide, for example acaricide, fungicide , antimicrobial and herbicidal, preferably insecticidal action.

The compounds of formula 1 are further valuable intermediates in the preparation of other new and known biologically active aromatic sulfoxide derivatives, such as benzimidazole and substituted diaminosulfoxide derivatives with anthelmintics and fungicidal activity, eg oxfendazole. They can be prepared from the corresponding compounds of the invention by reaction with an amine derivative, then by reduction and coupling with a carbamic acid derivative.

Compounds of formula 1 of the formula sheet are new. In the hitherto known nitro-substituted diaryl sulfoxides, the nitro groups were bound to one of the phenyl rings in ortho or para position relative to the sulfoxide group, while the other substituents were different from those in the compound of the invention, both Regarding quality, number and position relative to the sulfoxide group; while the only known compound with an o-nitro group was unsubstituted. The structurally related, known diarylsulfoxides were generally prepared by a different procedure, ie oxidation of the corresponding diarylsulfides / Ber. 4J_, 2836 (1908), J. Am. Chem. Soc. 1381 (1948_) _ 7 *

In formula 1 of the formula sheet, R and 2 R represent as halogen fluorine, chlorine, bromine or iodine, preferably chlorine; while by alkoxy having 1-6 carbon atoms is meant any straight or branched chain alkoxy group, eg methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec-butoxy, isobutoxy, n-pentoxy, isopentoxy, n-hexyloxy, iso hexyloxy, etc., preferably methoxy. In the definition of R, the term "alkyl of 1-6 carbon atoms" refers to straight chain 2 8500548 - 3 - * * & .- Λ 4 4 branched alkyl groups, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, etc.

In the compounds of formula 3 of the formula-5 sheet, wherein M is an alkali metal, M preferably refers to potassium or sodium.

In the compounds of formulas 2 and 5 of the formaldehyde sheet, where X and X represent halogen, they refer to fluorine, chlorine, bromine or iodine, preferably chlorine.

The intermediates of formula 5 of the formula sheet are new compounds, while their preparation also falls within the scope of the present invention.

The reduction of the arylsulfonyl halides of formula 2 of the formula sheet with alkali metal sulfites is preferably carried out in an aqueous medium, using the alkali metal sulfite in a slight excess, preferably in an amount of 1.1-4 moles per 1 mole of aryl sulfonyl halide. The reduction is carried out at 20-35 ° C, preferably at 22-28 ° C. The reduction is preferably carried out under mild alkaline conditions at a pH of 7-9, preferably 7.5-8.5, for example by addition to the reaction mixture of an alkali metal bicarbonate, alkali metal carbonate or alkali metal hydroxide simultaneously.

Alternatively, the above-mentioned agents can be added to the reaction mixture prior to the addition of the reducing agent. The alkali metal components of the above reagents are preferably identical to the alkali metal of the alkali metal sulfite used as the reducing agent. The above-mentioned alkalis also function as an acid-binding agent. The alkali metal bicarbonates, carbonates or hydroxides can be used either in a solid form or in the form of a saturated aqueous solution or simultaneously in both forms.

The acid treatment of the compounds of the formula III of the formula sheet is preferably carried out using a strong mineral acid, preferably concentrated aqueous hydrochloric acid, sulfuric acid, etc. The mineral acid is preferably used in excess. The aryl sulfinic acid obtained after hydrolysis is very pure (has a purity of 8500548 4 * * · 4 "♦ of at least 98%) and stable in contrast to the aryl sulfinic acids previously prepared by various methods. Compounds of formula 4 of the formula sheet are produced in very high yield obtained, which yield is considerably higher than the yield which has hitherto been obtained using the known methods / Houben-Weyl, 9, 3077.

Both the aryl sulfinates of formula 3 and the aryl sulfinic acids of formula 4 can be reacted with a halogenating agent to yield the corresponding aryl sulfinyl halide of formula 5 of the formula sheet.

An inorganic or organic halogenating agent can be used as the halogenating agent. Inorganic halogenating agents are, for example, the compounds of sulfur and phosphorus with halogen or with halogen and oxygen. Typical examples of these compounds are thionyl chloride, phosphorus trichloride, phosgene, phosphorus pentachloride, phosphorus oxychloride and a combination of phosphorus oxychloride and chlorine. Organic halogenating agents are organic acid halides, such as oxalyl chloride. The arylsulfinyl halide of formula 5 of the formula sheet are new compounds which are considerably more stable than the variously substituted arylsulfinyl halides of the prior art.

During the reaction of the compounds of formula (5) of the formula sheet with the compounds of formula (6) of the formula sheet, any catalyst used as metal halide catalyst of the Lewis acid type may be used in the Friedel-Crafts acylation, for example, aluminum trichloride . In a preferred embodiment of the reaction, compounds of formula 5 of the formula sheet are reacted with the compounds of formula 6 of the formula sheet without isolation, immediately after elimination of the halogenating agent. The Lewis acid type metal halide catalyst is preferably used in an amount of 1.1-1.8 moles per 1 mole arylsulfinyl halide of formula 5 of the formula sheet. The reaction is carried out at a temperature between 0 ° C and 80 ° C, preferably 25 ° C and 42 ° C.

According to the method of the invention, the 40 new nitrodiarylsulfoxides are produced in high purity (at least 850054ε • w - 5 - 98%) and in a high yield (90-96% with respect to the corresponding arylsulfinic acid, and about 85% with respect to of the corresponding arylsulfonyl halide). The method according to the invention can be easily carried out, even on an industrial scale.

The reaction mixtures can be worked up according to conventional techniques, for example extraction, filtration, evaporation, precipitation with water, elimination of the solvent or excess reagents, decanting, etc.

The compounds of formula 1 of the formula sheet can be subjected to further purification, for example recrystallization, if desired. The solvents used for the recrystallization are selected depending on the solubility and crystallization properties of the compound to be crystallized.

The active compounds of formula 1 of the formula sheet can be processed for therapeutic applications. The invention therefore also relates to pharmaceutical preparations having as active ingredient at least one compound of formula 1 of the formula sheet mixed with pharmaceutical carriers and / or excipients. Carriers customary for this purpose, suitable for parenteral and enteral administration, as well as other additives may be used. Solid or liquid compounds can be used as carriers, for example water, gelatin, lactose, starch, pectin, magnesium stearate, stearic acid, talc, vegetable oils, such as peanut oil, olive oil, etc.

The compounds can be formulated into conventional pharmaceutical preparations, for example, in a solid (spherical and rectangular pills, dragees, for example hard gelatin capsules) or liquid state (injectable oily or aqueous solutions or suspensions). The amount of the solid support can be varied within wide limits, but it is preferably between 25 mg and 1 g.

The formulations may optionally contain conventional pharmaceutical additives such as preservatives, wetting agents, osmotic pressure adjustment salts, buffers, flavors and fragrances.

The preparations according to the invention may optionally contain 85 0 05 48-6 * compounds of formula 1 of the formula sheet in combination with other known active ingredients. The unit doses selected are dependent on the mode of administration. The pharmaceutical preparations are prepared using conventional techniques, which involve sieving, mixing, granulating, compressing or dissolving the active ingredients. The resulting preparations are then subjected to further conventional treatments, such as sterilization.

For use as pesticides, the compounds of formula 1 of the formula sheet are processed into conventional preparations, for example solutions, emulsions, soluble powders, suspensions, powdered preparations, aerosol preparations, suspension and emulsion concentrates, powders for 15 'seed dressing. The compounds can be used to impregnate natural and synthetic materials, and can be microcapsulated, using polymeric materials and materials suitable for coating seeds, or in compositions containing flammable fillings, such as smoke cartridges, trays, coils and hot or cold mist preparations, which can be applied by ULV (ultra-low volume) technique.

The pesticidal preparations can be prepared in a manner known per se, for instance by mixing the active ingredients with carriers, ie liquid solvents, liquefied gases and / or solid carriers under pressure. If desired, surfactants, emulsifiers and / or dispersants and / or foaming agents may also be added to the system. When water is used as the carrier, one can also use organic solvents as co-solvent. The liquid solvents are mainly aromatic compounds such as xylene, toluene or alkylnaphthalenes. chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzene, chloroethylene or methylene chloride; aliphatic hydrocarbons, such as cyclohexane or paraffins, such as mineral oil fractions, as well as alcohols, such as butanol or glycol and their ethers and ester; ketones, such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; strong 40 polar solvents, such as dimethylformamide, dimethyl- 8500548 • * - 7 - sulfoxide and water. Among liquefied gases as carriers can be mentioned, for example, aerosol propellants, such as halogenated hydrocarbons, butane, propane, nitrogen and carbon dioxide. As solid carriers, mention can be made, for example, of natural fossil powders, for example kaolin, clay earth, talc, limestone, quartz, attapul cast, montmorillonite or diatomaceous earth, while highly suitable dispersed silicic powders, alumina and silicates are synthetic fossil powders. As carriers for granulates, use can be made, for example, of crushed and fractionated natural stones, for example calcite, marble, pumice, sepiolite, dolomite, and granulates of inorganic and organic powders, such as granules prepared from organic materials, for example sawdust, coconut husks, corncob and tobacco stems. As emulsifiers and / or foaming agents, nonionic and anionic emulsifiers can be used, such as polyoxyethylene fatty acid ethers, polyoxyethylene fatty acid alcohol ethers, for example alkylaryl polyglycol ether, alkyl sulfonates, alkyl sulfates, aryl sulfonates and protein hydrolyzates, for example as dispersants lignin, sulfite waste liquids and methyl cellulose can be taken.

The pesticidal compositions according to the invention may contain as adhesives carboxymethyl cellulose, natural and synthetic, powdery, granular or latex-like polymers, for example acacia gum, polyvinyl alcohol, polyvinyl acetate, etc.

The pesticidal preparations according to the invention may further contain various pigments, such as inorganic pigments, for example iron oxide, titanium oxide, ferrocyanic blue and organic pigments, for example alizarin, azo-metal phthalocyanine pigments, as well as micronutrients, for example iron, manganese, boron, copper, cobalt , molybdenum and zinc salts.

The pesticidal preparations generally contain 0.1-95% by weight, for example 0.5-90% by weight, of active ingredient.

The active ingredients can be used in the form of commercial preparations and / or 8500548 * 8 prepared therefrom.

The active ingredient concentration of the ready-to-use preparations prepared from the commercial pesticide preparations may vary within wide limits and generally occur therein in an amount between 0.000.000 l and 95 wt%, preferably 0.01- 10 wt%.

The mode of administration depends on the specific preparation used.

The invention is further illustrated by the following non-limitative examples.

EXAMPLE I

Sodium 4-chloro-3-nitro-benzene sulfinate

To a solution of 24 g of sodium bicarbonate in 30 ml of water was added 71.8 g (0.57 mol) of solid anhydrous sodium-15 sulfite. To the homogeneous solution, a mixture of 58.4 g (0.228 mol) of 4-chloro-3-nitro-benzenesulfonyl chloride and 24 g of sodium bicarbonate was added gradually over 23 hours at 23-25 ° C. After completion of the addition, the suspension was stirred at 23-25 ° C for 4 h and then 200 ml of toluene was added at 35 ° C for 15 min. Then the mixture was cooled to 23-25 ° C with stirring. The product was filtered off and air dried.

56 g of sodium 4-chloro-3-nitro-benzene-25 sulfinate were obtained. According to the potassium permanganate analytical method, the product contained 85% of the active ingredient and 15% water.

Yield; 90% of the theory.

EXAMPLE II

30 4-Chloro-3-nitro-benzenesulfinic acid

The sodium salt, prepared according to Example I, was dissolved in 300 ml of water at 40 ° C and filtered at the same temperature. The filtrate was cooled to 10-15 ° C, then acidified with 100 ml concentrated aqueous hydrochloric acid solution with thorough stirring, cooled to 5 ° C, filtered, the product obtained being dried at a temperature not exceeding 40 ° C .

- 85 0 05 48 - 9 -

43 g of white, crystalline 4-chloro-3-nitro-benzenesulfinic acid were obtained.

Purity: 9 9%

Melting point: 10-103 ° C.

Yield based on the sulfonyl chloride: 85% of theory.

EXAMPLE III

Phenyl- (4-chloro-3-nitrophenyl) sulfoxide a) 36 g (0.1625 mol) 4-chloro-3-nitro-benzenesulfinic acid prepared according to Example II, 75 ml of benzene and 15.1 ml of thionyl chloride mixed together. The reaction mixture was boiled for one hour and then distilled under vacuum at a temperature below 60 ° C.

Two further 25 ml portions of benzene 15 were added to the residue, each time the solvent was removed.

24

To the residue weighing about 40 g (nD - 1.6240), which is the crude 4-chloro-3-nitro-benzenesulfonyl chloride, was added 20 ml of dichloroethane, followed by addition of 28.2 g ( 0.21 mol) aluminum chloride under cooling at a temperature below 40 ° C. Then 35 ml of benzene was added to the mixture at 40 ° C over half an hour. The reaction mixture was stirred at 40 ° C for 2 h, then diluted with 50 ml of benzene, then poured into a mixture of 100 g of ice and 50 ml of water, finally extracting the organic phase with 50 ml of benzene. The combined benzene phases were decolorized with 5 g of charcoal, filtered and the solvent was eliminated from the filtrate under vacuum.

45 g of white phenyl (4-chloro-3-nitro-30 phenyl) sulfoxide were obtained.

Melting point: 86-87 ° C.

Purity: 98% (according to the high pressure liquid chromatography).

Yield: 96% of the theory.

B) 36 g (0.1625 mol) of 4-chloro-3-nitro-benzenesulfinic acid prepared according to Example 2 were mixed together, 20 ml of dichloroethane, 13.5 ml (22 g, 0.185 mol) of thionyl chloride and 0, 1 ml of triethylamine. The sulfic acid dissolved gradually, under gas evolution. The reaction mixture was heated to 50 ° C for one hour, then cooled to 5-10 ° C, and 28.2 g (0.21 mol) of aluminum chloride was added to the solution, taking care to ensure that the temperature of the reaction mixture did not rise above 40 ° C. Then, 35 ml of benzene was added to the mixture at 40 ° C over half an hour. The reaction mixture was stirred at 40 ° C for 2 h, then diluted with 50 ml of benzene and then poured onto a mixture of 100 g of ice and 50 ml of water. The organic phase was separated and the aqueous phase was extracted with 50 ml of benzene. The combined benzene phases were decolorized with 5 g of active carbon, followed by filtration, after which most of the benzene was removed from the filtrate by distillation under vacuum after a solid had precipitated. The remaining benzene was then removed with methanol under atmospheric pressure, so that the reaction mixture contained 60-70 ml of methanol. The solution was then allowed to cool slowly. Crystallization had started at 40-50 ° C. At the time the product gave a thick crystal slurry, 100 ml of water at a temperature of 40-50 ° C was added to the mixture at 40-50 ° C, initially at a low speed.

The loose finely divided suspension was cooled to 15-20 ° C with vigorous stirring, filtered and dried.

45 g of the desired compound were obtained. The physical properties of the product were identical to those of the product prepared according to variant a).

EXAMPLE IV

Phenyl (4-chloro-3-nitrophenyl) sulfoxide.

23 g (0.08 mol) of 84.7% sodium 4-chloro-3-nitrobenzenesulfinate, prepared according to Example I, were dissolved in 50 ml of benzene. 9.2 ml (0.112 mol) of phosphorus trichloride and 10 ml of benzene were added to the solution at a temperature below 30 ° C and with vigorous stirring for about 1.5 h. The mixture was stirred for an additional 2.5 h at 22-25 ° C, after which the benzene solution of the sulfinyl chloride derivative was decanted or filtered under vacuum. From the resulting solution, the solvent 8500548-11 was removed in vacuo and the distillation was repeated with two 20 ml portions of benzene. The light yellow oily 24 sulfinyl chloride derivative (n ^ = 1.6250) was diluted with 18 ml of benzene, followed by addition to the suspension of 11.34 g (0.085 mol) aluminum chloride in 18 ml of benzene at a temperature below 15 ° C. After completion of the addition, the temperature of the reaction mixture was allowed to rise to 40 ° C, at which temperature the reaction mixture was stirred for 2 h. The reaction mixture was then poured onto 100 ml of ice water. The isolated aqueous phase was extracted with 25 ml of benzene. The combined benzene phases were decolorized with activated charcoal, filtered and then the filtrate was evaporated in vacuo.

21 g of the desired compound were obtained.

Melting point: 86-87 ° C.

Yield: 95% of the theory.

EXAMPLE V

(4-Chloro-3-nitrophenyl) -4-methylphenylsulfoxide 20 To about 40 g of benzene and thienyl chloride-free 4-chloro-3-nitrobenzenesulfinyl chloride, prepared according to Example III, 100 ml of toluene and then 28.2 g ( 0.21 mol) aluminum chloride added at 20 ° C with cooling. The reaction mixture was stirred at 35 ° C for 2.5 h and then treated as in Example III.

42 g of the desired compound were obtained.

Melting point: 82-84 ° C.

Yield: 87% of the theory.

EXAMPLE VI

(4-Chloro-3-nitrophenyl) -4-chlorophenyl sulfoxide

The procedure described in Example V was repeated, except that chlorobenzene was used instead of toluene, and the reaction mixture was stirred at 50 ° C for 4 h. The title compound was obtained in a yield of 89%.

Melting point: 110-112 ° C.

8500548 '' - 12 -

EXAMPLE VII

Phenyl- (4-methoxy-3-nitrophenyl) sulfoxide 4-Methoxy-3-nitrobenzenesulfonyl chloride (melting point: 66 ° C) was reduced with sodium sulfite as described in Example 5I, after which the sodium 4-methoxy-3-nitro benzene sulfinate was further treated in the manner described in Example IV.

The title compound was obtained in a yield of 88%. Melting point: 135-137 ° C.

10

EXAMPLE VIII

2-Chloro-5-nitrobenzenesulfinic acid 321 ml (4.7 mol) chlorosulfonic acid and 79 g (0.5 mol) 4-chloro-nitrobenzene were stirred at 130 ° C for 6 h. The reaction mixture was then cooled to below 10 ° C and poured onto 750 ml of ice water. The mixture was filtered at room temperature, then the substance was collected on the filter and washed with approx. 2 L of water without acid. The crude 2-chloro-5-nitrobenzenesulfonyl chloride obtained was subjected to the following reaction steps without purification. 118 g (0.935 mol) of anhydrous sodium sulfite and 20 g of sodium bicarbonate were dissolved in 250 ml of water, followed by a mixture of the crude 2-chloro-5-nitrobenzenesulfonyl chloride and 20 g of sodium bicarbonate in the course of 1 h at the solution thus obtained. a temperature of 23-25 ° C was added. The reaction mixture was stirred at a temperature of 23-25 ° C for 2 h, after which the reaction mixture was stirred for an additional 15 min after the addition of 200 ml of toluene. The mixture was stirred at 25 ° C and the substance was filtered off, then washed with 100 ml of toluene. The resulting sodium 2-chloro-5-nitrobenzene sulfinate was dissolved in 400 ml of water at 40 ° C, after which the solution was mixed with 200 ml of toluene. The insoluble part was filtered off and the toluene phase of the filtrate was separated. The water phase was cooled to 10 ° C, acidified with 100 ml of concentrated aqueous hydrochloric acid solution, and the crystals formed were stirred, filtered at 10 ° C and dried. 61 g of 2-chloro-5-nitrobenzenesulfinic acid were obtained. Yield: 55% of theory based on 8500548 - 13 - on the 4-chloro-nitrobenzene.

Melting point: 128-130 ° C.

Purity: 98% (according to the potassium permanganate analytical method).

EXAMPLE IX

Phenyl (2-chloro-5-nitrophenyl) sulfoxide 26 g (0.1625 mol) 2-chloro-5-nitrobenzenesulfinic acid was mixed with 60 ml of benzene and 36 ml of thionyl chloride. The reaction mixture was boiled for 1 h. Subsequently, the procedure described in Example III was followed, except that instead of benzene, dichloroethane was used for dilution and extraction.

This gave 40 g of phenyl (2-chloro-5-nitrophenyl) sulfoxide in the form of a white microcrystalline substance.

Melting point: 150-152 ° C.

Purity: 97% (according to the high pressure liquid chromatography).

Yield: 85% of the theory.

EXAMPLE X

4- (4-Chloro-3-nitrobenzenesulfinyl) biphenyl

The procedure of Example V was repeated, except that biphenyl was used instead of toluene. The desired compound was obtained in a yield of 90%.

Melting point: 98-99 ° C.

EXAMPLE XI

4- (4-Chloro-3-nitrophenylthio) -phenyl- (4-chloro-3-nitrophenyl) sulfoxide 30 36 g (0.1625 mol) 4-chloro-3-nitrobenzenesulfinic acid, prepared according to example II, 35 ml of benzene, 10.5 ml (0.143 mol) of thionyl chloride and 0.1 g of anhydrous ferric chloride were boiled for one hour. At a temperature below 40 ° C, 28.2 g (0.21 mol) of aluminum-35 chloride was added to the solution. The reaction mixture was stirred at 40 ° C for 2 h, after which the pro- 8500548 yr *. -14- described in Example III.

procedure was followed. The resulting oily product was dissolved in hot acetone, then a small amount of aqueous methanol was added to the solution, the separated oil was dissolved in hot acetone and again treated with aqueous methanol. The oily part was isolated. After addition of acetone, the desired compound was obtained in crystalline form.

11.4 g of the title compound were obtained.

10 Yield; 30% of theory Melting point: 144-146 ° C.

EXAMPLE XII

(4-Chloro-3-nitrophenyl) -4-methoxyphenyl sulfoxide

The reaction mixture containing 4-chloro-3-nitrobenzenesulfinyl chloride, prepared in the manner described in Example III, variant b), was freed from thionyl chloride by distillation under vacuum. 50 ml of dichloroethane and 21.6 g of anisole were added to the residue, after which the mixture was cooled to -5 ° C and at which temperature 33.4 g of aluminum chloride was added portionwise, ensuring that the temperature of the mixture did not exceed 20 ° C. The reaction mixture was then kept at 20 ° C for 4 h, poured onto 300 ml of ice water, extracted with dichloroethane and the solvent removed from the organic solvent phase under vacuum.

46.5 g of (4-chloro-3-nitrophenyl) -4-methoxyphenyl sulfoxide were obtained.

Yield: 92% of the theory.

Melting point: 124-126 ° C.

EXAMPLE XIII

(4-Chloro-3-nitrophenyl) -4-fluorophenyl sulfoxide

To about 40 g of crude, benzene and thionyl chloride-free 4-chloro-3-nitrobenzenesulfinyl chloride prepared according to one of the variants of Example III, 90 ml of fluoro-35 benzene was added, followed by the addition of 33.6 g of aluminum chloride under cooling. The reaction mixture was stirred at 55 ° C for 5 h and then treated in the manner described in Example III, 05 05 - 15 - 15, provided that the reaction mixture was not diluted with benzene.

42 g of the desired compound were obtained. Yield: 86% of the theory.

5 Melting point: 84-85 ° C.

EXAMPLE XIV

(4-Bromophenyl) - (4-chloro-4-nitrophenyl) sulfoxide

100 ml of bromobenzene were added to about 40 g of crude 4-chloro-3-nitrobenzenesulfinyl chloride prepared according to one of the variants of Example III. 33.6 g of aluminum chloride was added to the mixture under cooling, which mixture was then stirred at 50 ° C for 3 h and further treated in the manner described in Example III, except that benzene was added to the reaction mixture after pouring into water. and the excess bromobenzene was removed from the reaction mixture by distillation at 60-70 ° C under a pressure of 30-40 mmHg.

54.5 g of the desired compound are obtained.

20 Yield: 93% of the theory.

Melting point: 138-140 ° C.

EXAMPLE XV

4-Chlorophenyl- (2-chloro-5-nitrophenyl) sulfoxide 36 g (0.1625 mol) 2-chloro-5-nitrobenzenesulfin-25 acid, prepared according to example VIII, was converted into 2-chloro-5-nitrobenzenesulfinyl chloride on the manner described in example III. Then it was liberated from benzene and thionyl chloride, diluted with 100 ml of chlorobenzene, and 28.2 g of aluminum chloride was added to the mixture with stirring. The reaction mixture was stirred at 55 ° C for 5 h and then treated in the manner described in Example III, except that the dilution with benzene was carried out only after pouring into water.

44 g of the desired compound were obtained.

Yield: 86% of the theory.

Melting point: 142-144 ° C.

85 0 05 48 * '- 16 -

EXAMPLE XVI

(4-Ethoxy-3-nitrophenyl) -phenyl sulfoxide

The procedure of Example VII was repeated, except that 4-ethoxy-3-nitro-5-benzenesulfonyl chloride was used as starting material and sodium 4-ethoxy-3-nitrobenzenesulfinate was prepared therefrom in the manner described in Example I in a yield. 70%, which was then further treated as described in Example IV.

The desired compound was obtained in 86% yield.

Melting point: 119-121 ° C.

EXAMPLE XVII

1- (4-Bromophenyl) -4- (4-chloro-3-nitrophenylsulfinyl) -benzene The procedure described in Example V was repeated except that instead of toluene 4- bromobiphenyl used. The desired compound was obtained in 80% yield.

Melting point: 173-175 ° C.

EXAMPLE XVIII

(4-Chloro-3-nitrophenyl) -4-methylthiophenyl sulfoxide

The procedure described in Example V was repeated, except that thioanisole was used instead of toluene.

EXAMPLE XIX

25 1- (4-Nitrophenyl) -4- (4-chloro-3-nitrophenylsulfinylbenzene)

The procedure of Example V was repeated, except that toluene was replaced with 4-nitro-biphenyl.

The title compound was obtained in a yield of 50%.

Melting point: 220-222 ° C.

8500548

Claims (17)

A process for the preparation of nitrodiarylsulfoxides of formula 1 of the formula sheet, wherein 1 R is halogen or alkoxy with 1-6 carbon atoms, 2 R hydrogen, halogen, alkyl with 1-6 carbon atoms, 5 alkoxy with 1-6 carbon atoms , or phenyl or phenylthio optionally substituted by one or more equal or different halogen (halogens) and / or nitro group (s), characterized in that an arylsulfonyl halide of formula 2 of the formula sheet, wherein 1 R represents the above meaningful, and X being halogen, is reduced with an alkali metal sulfite, after which the resulting aryl sulfinate of formula 3 of the formula sheet, wherein R has the above meaning, and M is an alkali metal, is treated with an acid, after which the aryl sulfide obtained fine acid of formula 4 of the formula sheet, wherein R1 has the above meaning, or the aryl sulfinate of formula 3 of the formula sheet, wherein R and M have the above meanings, w is treated with a halogenating agent, after which the new arylsulfinyl halide of formula 5 of the formula sheet obtained herein, wherein 25 has the above meaning and is 2 X halogen, is reacted with a benzene derivative of formula 6 of the 2 formula sheet, where R has the above meanings. 2. Process according to claim 1, characterized in that during the reduction 1.1 to 4 moles of an al potassium metal sulfite are used on 1 mole of arylsulfonyl halide of formula 2 of the formula sheet, wherein R 1 and X 1 are as defined in claim 1 have defined meanings. 3. Process according to claim 1 or 2, characterized in that the reduction of an arylsulfonyl halide of formula 2 of the formula sheet, in which R and X have the meanings stated in claim 1, is carried out at 20-50 ° C. 8500548 ~ w - 18 - 4. Process according to any one of the preceding claims 1-3, characterized in that the reduction of an aryl-sulfonyl halide of formula 2 of the formula sheet, wherein R and X have the meanings defined in claim 1, is carried out in a slightly alkaline medium. 4. - 17 - 5. Process according to claim 1, characterized in that the aryl sulfinate of formula 3 of the formula sheet, wherein R and M have the meanings defined in claim 1, is treated with an excess of a strong mineral acid. 6. Process according to claim 1, characterized in that the arylsulfinyl halide of formula 5 of the formula sheet wherein R and X have the meanings defined in claim 1 is reacted with the benzene derivative of formula 6 of the formula sheet, wherein R has the meaning defined in claim 1 after eliminating the excess halogenating agent without isolating. 7. Process according to claim 1 or claim 6, characterized in that in the reaction of an aryl sulfinyl halide of formula 5 of the formula sheet, wherein 1 2 R and X have the meanings defined in claim 1, with a benzene derivative of formula 6 of the formula sheet, 2 wherein R has the meanings defined in claim 1, when Lewis acid is used 1.1-1.8 mol aluminum chloride per 1 mol aryl-sulfinyl chloride. 8. Process according to claims 1,6 and 7, characterized in that the reaction of an arylsulfinyl halide of formula 5 of the formula sheet, wherein R and 2 X have the meanings defined in claim 1, with a benzene derivative of formula 6 of the formula sheet, where-2 in R has the meanings defined in claim 1, is performed at a temperature between 0 ° C and 80 ° C. 9. Process for the preparation of pharmaceutical preparations, characterized in that a nitrodiaryl sulfoxide of formula 1 of the formula sheet, wherein R and R have the meanings defined in claim 1, is reacted with at least one conventional pharmaceutical carrier and / or other additive. 10. Nitrodiarylsulphoxides of formula 1 of the formula sheet, wherein 8500548-19 - β; "β ψ" t represents R halogen or alkoxy of 1-6 carbon atoms, 2 R hydrogen, halogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, or phenyl or phenylthio optionally substituted by one or more 5 represents different or different halogen (halogens) and / or nitro group (s). 11. Compound selected from the following group of compounds: phenyl- (4-chloro-3-nitrophenyl) sulfoxide, 10 (4-chloro-3-nitrophenyl) -4-methylphenyl sulfoxide, (4-chloro-3-nitrophenyl) -4- chlorophenyl sulfoxide, phenyl (4-methoxy-3-nitrophenyl) sulfoxide, phenyl (2-chloro-5-nitrophenyl) sulfoxide, (4-chloro-3-nitrophenyl) -4-biphenylyl sulfoxide, 15 (4-chloro-3- nitrophenyl) -4-methoxyphenyl sulfoxide, (4-chloro-3-nitrophenyl) -4-fluorophenyl sulfoxide, 4-bromophenyl- (4-chloro-3-nitrophenyl) sulfoxide, 4-chlorophenyl- (2-chloro-5-nitrophenyl) sulfoxide , (4-ethoxy-3-nitrophenyl) -phenylsulfoxide, 1- (4-bromophenyl) -4- (4-chloro-3-nitrophenylsulfinyl) benzene, 1- (4-nitrophenyl) -4- (4-chloro-) 3-nitrophenylsulfinyl) benzene, 4- / T4-chloro-3-nitrophenylthio) -phenyl7- (4-chloro-3-nitro-phenyl) sulfoxide. 12. Pharmaceutical preparation, characterized in that this active ingredient contains at least one compound of formula 1 of the formula sheet, wherein R1 and 2 R have the meanings defined in claim 10, in addition to pharmaceutical carriers and / or excipients. 13. Pesticidal composition, characterized in that it as active ingredient is a nitrodiarylsulfoxide of the formula 1 of the formula sheet, wherein R 1 is halogen or alkoxy of 1-6 carbon atoms, 2 R hydrogen, halogen, alkyl of 1-6 carbon atoms, alkoxy with 1-6 carbon atoms, or phenyl or phenyl-35 thio optionally substituted by one or more equal or different halogen (halogens) and / or nitro group (s), mixed with one or more solid and / or liquid carrier and optionally other additives. 8500548 - 20 - 14. Preparation according to claim 13, characterized in that it contains as active ingredient a compound of formula 1 of the formula sheet, in which R and R have the meanings defined in claim 13, in an amount of 0.1 -95 wt%. 15. A process for the preparation of arylsulfinyl halides of formula 5 of the formula sheet, wherein 1 R is halogen or alkoxy of 1-6 carbon atoms, 2 R represents halogen, characterized in that an arylsulfonyl halide of formula 2 of the formula sheet, wherein R has the previously defined meaning, X is halogen, is reduced with an alkali metal sulfite, followed by hydrolysis of the aryl sulfinate of formula 3 of the formula sheet obtained herein, wherein 1 R has the above meaning and M represents an alkali metal atom, followed by conversion of the aryl sulfinic acid of formula IV of the formula sheet wherein R has the above meaning, or the aryl sulfinate of formula 3 of the formula I sheet wherein R and M have the above meanings with an inorganic acid chloride. 16. Compounds of formula 5 of the formula sheet, wherein 1 R represents halogen or alkoxy of 1-6 carbon atoms, 2 X is halogen. 17. Method for the treatment of mammals, including humans, characterized in that a therapeutically effective amount of a nitrodiarylsulfoxide of the formula 1 of the formula sheet, wherein 1 R is halogen or alkoxy of 1-6 carbon atoms, 2 R hydrogen, halogen, alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, or phenyl or phenyl-thio optionally substituted by one or more equal or different halogen (halogens) and / or nitro group (s). 8500548