HU195949B - Process for producing new nitro-diaryl-sulfoxide derivatives and pharmaceutics comprising such compounds - Google Patents

Abstract

Nitrodiaryl sulfoxides of the formula (I), <IMAGE> wherein R<1> is halogen or C1-6 alkoxy, R<2> is hydrogen, halogen, C1-6 alkyl, C1-6 alkoxy, or phenyl or phenylthio optionally substituted by one or more identical or different halogen(s) and/or nitro group(s), show pesticidal activity and are of particular use in human and veterinary therapy, preferably as anthelmintics.

Description

The present invention relates to novel nitro-diaryl sulfoxides of the formula I in which R ¹ is halogen or C 1 -C 4 alkoxy, R ² is hydrogen, halogen, C 1 -C 4 alkyl, C 1 -C 4 alkoxy, optionally halogen or nitro substituted phenyl, such that an arylsulfonyl halide of formula (II) wherein R ¹ is as defined for formula (I) and X ¹ is halogen reduced with an alkali metal sulfite, the (III) arilszulfinátot formula - wherein R ¹ are as in formula (I) as defined and M represents an alkali metal - is treated with an acid to obtain the (V) arylsulfinic acid of formula - wherein R ¹ is an aryl of formula (I) or aryl of formula (III) the sulfinate, wherein R ¹ and M are as defined above, is reacted with a halogenating agent and the resulting arylsulfinyl halide of formula (V), wherein R ¹ is as defined for formula (I) and X ² is halogen, is a Lewis reacting - (VI) benzene derivative of formula -acid type metal halide catalyst - wherein R ² are as in formula (I) defined above.

The novel compounds of formula (I) have therapeutic properties, particularly useful in veterinary medicine, and possess pesticidal, in particular insecticidal, properties including acaricides, fungicides and herbicides.

In addition, the compounds of formula I are valuable intermediates for other bioactive aromatic sulfoxide derivatives.

The compounds of formula I are novel. To date, only diaryl sulfoxides containing a nitro group have been known to have a nitro group on one of the phenyl rings in a position other than the meta-position, and the quality, quantity and content of the other substituents on the sulfoxide group. were different from the compounds of formula (I) obtained by the process of the present invention, and had no other substituents in the meta-position of the nitro group. Hitherto, diaryl sulfoxides other than the novel compounds of formula (I) obtained by the process of the present invention have generally been prepared by oxidation of the corresponding diaryl sulfides in a manner other than that of the present invention. 41, 2836 (1908), J. Am. Chem. Soc. 70, 1381 (1948)].

In the formula (I), R ¹ and R ² are selected from the group consisting of fluorine, chlorine, bromine or iodine, preferably chlorine, C 1 -C 4 -alkoxy, any straight or branched alkyl group, such as methoxy, ethoxy, η-propoxy, i-propoxy, η-butoxy, sec-butoxy, tert-butoxy, i-butoxy, preferably methoxy. R ^{2 is a C} 1-4 alkyl group which may be straight or branched chain, such as methyl, ethyl, n-propyl, i-propyl, η-butyl, sec-butyl, tert-butyl, ΐ- butyl, groups,

In the compounds of formula (III), M may be an alkali metal or potassium or sodium atom.

In the compounds of formula (II) and (V), X ¹ and X ^{2 as} halogen may be fluorine, chlorine, bromine or iodine, preferably chlorine.

The intermediates of formula (V) are novel.

The reduction of the arylsulfonyl halides of formula II with alkali metal sulfites is conveniently carried out in an aqueous medium using 1.1 to 4 moles of alkali metal sulfite per small molar excess of the alkali metal sulfite. The reduction can be carried out at 2025 ° C, preferably 22-28 ° C. The reduction is conveniently carried out under mildly basic conditions, preferably in the pH range of 7 to 9, preferably 7.5 to 8.5, for example by adding to the reaction mixture an alkali metal hydroxide, preferably the same as the alkali metal of the alkali metal sulfite. we insert it in advance. These basic agents simultaneously serve as an acid scavenger. The alkali metal bicarbonate, carbonate or hydroxide may be used in solid form, in the form of a saturated aqueous solution, or in both forms.

The acid treatment of the compounds of formula (III) may conveniently be carried out with a strong mineral acid, preferably concentrated aqueous hydrochloric acid, sulfuric acid and the like. The mineral acid used is preferably used in excess. The arylsulfinic acid of formula (IV) obtained after hydrolysis is very pure (at least 98% pure) and extremely stable, unlike other arylsulfinic acids obtained by a different process, as previously known. The yields of the compounds of formula (IV) are also very high, exceeding the methods known hitherto (Houben-Weyl Vol. 9, p. 307).

Both the arylsulphinate (III) and the arylsulphinic acid (IV) can be reacted with a halogenating agent to give the corresponding arylsulphinyl halide (V). The halogenating agent may be an inorganic or organic halogenating agent. Inorganic halogenating agents include, for example, halogen compounds of sulfur or phosphorus, or compounds of halogen and oxygen. Examples of such compounds are thionyl chloride, phosphorus trichloride, phosgene, phosphorus pentachloride, phosphorus oxychloride and chlorine. An organic halogenating agent is, for example, an organic acid halide such as oxalyl chloride. The arylsulfinyl halides of formula (V) are novel compounds and are substantially more stable than other, differently substituted, known arylsulfinyl halides.

The Lewis acid halide catalyst used in the reaction of the compounds of formula (V) and (VI) may be any conventional catalyst for Friedel-Grafts acylation, such as, for example, aluminum trichloride. The reaction may also be carried out by reacting compounds of formula (V) with compounds of formula (VI) without isolation, only after removal of the halogenating agent. The reaction may conveniently be carried out using 1.1 to 1.8 moles of Lewis acid metal halide catalyst per mole of arylsulfinyl halide of formula (V). The reaction may be carried out at a temperature of from 20 to 80 ° C, preferably from 25 to 42 ° C.

The process of the present invention is prepared in a very pure state (at least 98% purity), in a range of about 90-96% based on the corresponding arylsulfinic acid, and about 90% on the corresponding arylsulfonyl halide. In 85% yield, nitrodiaryl sulfoxides of formula (I). Certain operations of the process according to the invention can be carried out simply on an industrial scale.

Work-up of the reaction mixtures can be carried out by known methods, such as extraction, filtration, evaporation, aqueous precipitation, removal of solvent or excess reagent, decantation, etc.

If desired, the compounds of formula (I) obtained by the process of the present invention may be subjected to further purification operations, such as, e.g. The range of solvents that can be recrystallized is determined by the solubility and crystallization properties of the material to be crystallized.

The active ingredient of formula (I) may be formulated in pharmaceutical compositions with non-toxic, inert, solid or liquid carriers and / or excipients suitable for parenteral or enteral administration in the pharmaceutical field. Suitable carriers include, for example, water, gelatin, lactose, lactose, starch, pectin, magnesium stearate, stearic acid, talc, vegetable oils such as peanut oil, olive oil, and the like. It can be used. The active ingredient may be in the form of standard pharmaceutical compositions such as solid (round or square tablets, dragees, capsules such as hard gelatin capsules, pills, suppositories, etc.) or liquid (e.g., oily or aqueous solution, suspension, emulsion, syrup, soft gelatin capsules, injectable oily or aqueous solutions or suspensions, etc.). The amount of solid carrier can vary widely, preferably from about 25 mg to about 1 g. The compositions may optionally contain conventional pharmaceutical excipients, such as preservatives, stabilizers, wetting agents, emulsifying agents, salts for adjusting osmosis, buffering agents, flavoring agents, perfumes, and the like. may also be included. The compositions may also optionally contain other pharmaceutically valuable compounds without exhibiting synergistic effects. Preferably, the composition is formulated in dosage units appropriate to the desired route of administration. The pharmaceutical compositions may be prepared by conventional methods, which include, for example, sifting, mixing, granulating, and pressing or dissolving the ingredients in the appropriate compositions. The compositions may be subjected to other conventional pharmaceutical operations (e.g., sterilization).

For use as pesticides, the active compounds of formula (I) may be formulated in conventional formulations such as solutions, emulsions, soluble powders, suspensions, powder formulations, aerosol formulations, suspension and emulsion concentrates, and seed coatings. Cultures and synthetic materials can be impregnated therewith, with the aid of polymeric materials and seed coatings, microcapsules can be prepared, and the active ingredients may also be formulated with flammable fillers, such as fume cartridges, cans and spirals, or hot or cold .

Pesticide formulations containing the active compounds of formula (I) may be prepared in a manner known per se, for example, by mixing the active compounds with excipients, i.e., liquid solvents, pressurized liquid gases and / or solid carriers, optionally surfactants, i.e., emulsifiers and dispersing agents and / or foaming agents may also be added. When water is used as a carrier, organic solvents may also be used as co-solvents. Suitable liquid solvents are essentially 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 cyclohexanes or paraffins, and their ethers and esters, ketones such as acetone, methylethylketone, methylisobutylketone or cyclohexanone, highly polar solvents such as dimethylformamide, dimethylsulfoxide and water. Liquid gaseous carriers are understood to include materials such as aerosol propellants such as halogenated hydrocarbons, butane, propane, nitrogen and carbon dioxide. Of course, solid carriers include stone flour such as kaolin, clay, talc, chalk, quartz, attapulgite, montmorillonite or diatomaceous earth, as well as synthetic stone flour such as highly dispersed silica, alumina and silicates. Solid carriers for granules include granules made from diatomaceous earth and fractionated natural rocks such as calcite, marble, pumice, sepiolite, dolomite, inorganic and organic flours, and organic materials such as sawdust, coconut shells, corn cobs and tobacco stalks. Nonionic and anionic emulsifiers such as polyoxyethylene fatty acid ethers, polyoxyethylene fatty alcohol ethers such as alkylaryl polyglycolol ether, alkyl sulfonates, alkyl sulfates, aryl sulfones, aryl sulfones, are used as emulsifiers and / or foaming agents.

Pesticide formulations containing the active compounds of formula (I) may contain adhesion promoters such as carboxymethylcellulose, natural and synthetic, powdered, granular or latex-like polymers such as gum arabic, polyvinyl alcohol, polyvinyl acetate.

The pesticidal formulations containing the active compounds of the formula I further comprise coloring agents such as inorganic pigments, such as iron oxide, titanium dioxide, ferrocyanite and organic dyes such as alizarin, azo-metal phthalocyanine dyes, and printing materials such as iron, manganese, boron. , copper, cobalt, molybdenum and zinc salts.

The pesticidal compositions generally contain from 0.1 to 95% by weight, preferably from 0.5 to 90% by weight, of the active ingredient.

The active compounds are used in the form of commercially available formulations and / or forms thereof.

The active ingredient content of the formulations of the pesticidal formulations may be varied within wide limits. The concentration of active ingredient in the forms of use is between 0.000,000 and 95% by weight, preferably 0.01 to 10% by weight.

The application is carried out in a manner chosen according to the particular pesticide formulation.

The dermal fungicidal activity of the compounds of the present invention is shown in Table 1.

Table 1

MIC (Minimum Inhibition Concentration) value in µg / ml

compounds Epidermophyton KW Trichophyton terrestre Trichophyton gypseum Micro sports gypseum phenyl (4-chloro-3- nitro-phenyl) - sulfoxide 100 - 25 100 (4-Chloro-phenyl) - (6-chloro-3-nitrophenyl) sulfoxide - - - 12.5 (4-Fluorophenyl) (4-chloro-3-nitrophenyl) sulfoxide 100 50 50 100 (4-bromophenyl) - (4-chloro-3-nitro- phenyl) sulfoxide - 3,125 - - phenyl (5-chloro-2-nitrophenyl) sulfoxide (counterexample) - - - - According to the invention compounds anthelmintic the impact of Kush See Table 2 illustrates (dose:

100 mg / kg).

Table 2

Compound examined worm average handled worm numbers control efficiency % (4-Chloro-phenyl) -4-chloro-3-nitro- yarn 56.2 60.9 7.7 phenyl) sulfoxide gala d 11.0 18.8 41.5 (4-chloro-3-nitro- phenyl) biphenyl sulfoxide yarn 47.6 60.9 21.8

The insecticidal activity of the compounds of the invention is shown in Table 3. 1000 ppm of each compound its effect on certain pests is expressed as a percentage of mortality. spreadsheet Third Malware Dysdercus Megoura Phaedon Tetranychus Rhabdi- Musca cyngulatus viciae cochlea- urticae tis oxy- domes (gyapotpo- (vetch -riae (Two-spotted cerca tica Compound Loska) aphid) (horse-radish- beetle) mite) (saprophytic nematode species) (home Train) (4-chloro-3-fertilis- ro-phenyl) -bife- phenyl sulfoxide phenyl (6-chloro- 10% 5% 0% 80% 60% (dose here 25 ppm) 20% 3-nitro-phenyl) - sulfoxide phenyl (4-chloro- 10% 25% 0% 50% 50% (dose here 25 ppm) 10% 3-nitro-phenyl) - sulfoxide 0% 15% 40% 10% 0% 0% (4-methylphenyl) - - (4-Chloro-3-nitrophenyl) -sulfoxide 0% 10% 10% 20% 0% 0% (4-chlorophenyl) - - (4-Chloro-3-nitrophenyl) sulfide oxide 0% 0% 10% 30% 0% 0% phenyl (4-methoxy- 3-nitro-phenyl) - 0% 0% 60% 10% 0% 0%

sulfoxide

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

Example 1

Sodium-4-chloro-3-nitro-benzolszulfinát

To a solution of 340 mL water and 24 g sodium bicarbonate was added 71.8 g (0.57 mol) of solid

Anhydrous sodium sulfite was added. To the homogeneous solution was added a mixture of 58.4 g (0.228 mol) of 4-chloro-3-nitrobenzenesulfonyl chloride and 24 g of sodium bicarbonate at 23-25 ° C over 2 hours. After the addition was complete, the suspension was stirred at 2325 ° C for 4 hours, then toluene (200 mL) was stirred at 35 ° C for 15 minutes, cooled to 23-25 ° C and filtered. The filtered product is air dried.

56 g of sodium 4-chloro-3-nitrobenzylsulfinate are obtained, the potassium permanganate assay is 85% active and the water content is 15%.

The yield is 90% of theory.

Example 2

4-Chloro-3-nitrobenzenesulfonic acid

The sodium salt prepared in Example 1 was dissolved in 300 ml of water at 40 ° C and filtered at the same temperature. The filtrate, cooled to 10-15 ° C, was acidified with 100 ml of concentrated aqueous hydrochloric acid solution with vigorous stirring, cooled to 5 ° C, filtered, and the filtered product was dried below 40 ° C.

43 g of white crystalline 4-chloro-3-nitrobenzenesulfinic acid are obtained.

Active ingredient content: 99%.

102-103 ° C.

The yield is 85% of theory based on sulfonyl chloride.

Example 3

Phenyl (4-chloro-3-nitrophenyl) sulfoxide g (0.1625 mol) of 4-chloro-3-nitrobenzenesulfinic acid prepared in Example 2, 75 mL benzene and 15.1 mL thionyl chloride were added. The reaction mixture was refluxed for 1 hour and then distilled under vacuum at a temperature below 60 ° C. An additional 25 mL of benzene was added to the residue and the solvent was removed twice more. To about 40 g of the residue (nD ²⁴ = 1.6240) is added dichloroethane and 28.2 g (0.021 mole) of aluminum chloride are added to the solution while cooling at a temperature below 40 ° C, and the mixture is stirred at 40 ° C. 35 ml of benzene were added over an hour. After stirring for 2 hours at 40 ° C, the reaction mixture was diluted with benzene (50 mL) and poured into a mixture of ice (100 g) and water (50 mL), and the organic layer was separated and the aqueous was extracted with benzene (50 mL). The combined benzene phases were clarified with 5 g of carbon, filtered and the filtrate was evaporated in vacuo.

45 g of white phenyl (4-chloro-3-nitrophenyl) sulfoxide are obtained.

Melting point: 86-87 ° C.

Purity: 98% (by HPLC)

Yield: 96% of theory.

Example 4

Phenyl (4-chloro-3-nitrophenyl) sulfoxide g 84.7% sodium 4-chloro-3-nitrobenzenesulfinate (0.08 mol) prepared in Example 1 was dissolved in benzene (50 mL). A solution of phosphorus trichloride (9.2 mL, 0.112 mol) and benzene (10 mL) was added slowly to the solution at a temperature below 30 ° C with vigorous stirring over about 1.5 hours. The mixture was then stirred for an additional 2.5 hours at 22-25 ° C, and the benzene solution of the sulfinyl chloride spray was decanted or aspirated. The solution thus obtained is freed of solvent in vacuo and the distillate is repeated twice with 20 ml of benzene. The pale yellow oil-like sulfinyl chloride derivative (nD ²⁴ = 1.6250) was diluted with 18 mL of benzene and added at a temperature below 15 ° C to a suspension of 11.34 g (0.085 mol) of aluminum chloride and 18 mL of benzene. After the addition was complete, the reaction mixture was allowed to warm to 40 ° C and stirred at this temperature for 2 hours. The reaction mixture was then poured into 100 ml of ice water. The separated aqueous phase was extracted with 25 ml of benzene. The combined benzene phases are decolorized with carbon, filtered and the filtrate is evaporated in vacuo.

21 g of phenyl (4-chloro-3-nitrophenyl) sulfoxide are thus obtained.

Melting point: 86-87 ° C.

Yield: 95% of theory.

Example 5 (4-Chloro-3-nitrophenyl) (4-methylphenyl) sulfoxide

Benzene and thionyl chloride, prepared according to Example 3, were decontaminated with about 40 g of 4-chloro-3-nitrobenzenesulfinyl chloride under cooling at 20 ° C in 100 ml of toluene, followed by 28.2 g (0.21 mol). aluminum chloride is added. The reaction mixture was stirred at 35 ° C for 2.5 hours and worked up as described in Example 3.

42 g of the expected product are obtained.

M.p. 82-84 ° C.

Yield: 87% of theory.

Example 6 (4-Chloro-3-nitrophenyl) - (4-chlorophenyl) sulfoxide

In each case, the procedure described in Example 5 is followed except that

Chlorobenzene is used instead of -613 toluene.

The yield of the title compound thus obtained was 89% of theory.

Melting point: 110-112 ° C.

Example 7

Phenyl (4-methoxy-3-nitrophenyl) sulfoxide

4-Methoxy-3-nitrobenzenesulfonyl chloride (m.p. 66 ° C) was reduced with sodium sulfite in the same manner as in Example 1 and the resulting sodium 4-methoxy-3-nitrobenzenesulfinate was treated as described in Example 4. reaction.

Yield: 88% of theory.

135-137 ° C.

Example 8

2-chloro-5-nitro-benzenesulfinic

321 ml (4.7 mol) of chlorosulfonic acid and 79 g (0.5 mol) of 4-chloronitrobenzene are added. After stirring for 6 hours at 130 ° C, the reaction mixture is cooled to below 10 ° C and poured into 750 ml of ice water, filtered at room temperature, and the filter material is washed several times with about 2 liters of water to anhydrous. The crude product of 2-chloro-5-nitrobenzenesulfonyl chloride was taken to the next step without purification. Anhydrous sodium sulfite (118 g, 0.935 mol) and sodium bicarbonate (20 g) were dissolved in water (250 mL), and the crude 2-chloro-5-nitrobenzenesulfonyl chloride and crude 2-chloro-5-nitrobenzenesulfonyl chloride were added over 1 hour at 23-25 ° C. g of sodium bicarbonate. After stirring for 2 hours at 23-25 ° C, the reaction mixture is stirred with 200 ml of toluene for 15 minutes, filtered at 25 ° C and washed with 100 ml of toluene. The resulting sodium 2-chloro-5-nitrobenzenesulfinate was dissolved in 400 mL of water at 40 ° C and the solution was stirred with 200 mL of toluene, the insoluble material was removed by filtration, and the toluene layer was separated from the filtrate. The aqueous layer was cooled to 10 ° C, acidified with 100 ml of concentrated aqueous hydrochloric acid solution, and the precipitated crystals were stirred at 10 ° C and dried.

61 g of 2-chloro-5-nitrobenzenesulfinic acid are obtained.

Yield: 55% of theory based on 4-chloro-nitrobenzene.

128-130 ° C.

Active ingredient content of the product: 98% (as determined by the potassium permanganate method).

Example 9

Phenyl (2-chloro-5-nitrophenyl) sulfoxide g (0.1625 mol) of 2-chloro-5-nitrobenzenesulfinic acid, 60 mL of benzene and 36 mL of thionyl chloride were added. The reaction mixture is refluxed for 1 hour, followed by the same procedure as in Example 3, except that dichloroethane is used for dilution and extraction.

40 g of white microcrystalline phenyl (2-chloro-5-nitrophenyl) sulfoxide are thus obtained.

Melting point: 150-2 ° C.

Purity: 97% (by HPLC).

Yield: 85% of theory.

Example 10

4- (4-chloro-3-nitrobenzenesulfonyl) biphenyl

All of the procedures described in Example 5 were followed except that biphenyl was used in place of toluene.

Thus, the yield of the title compound is 90% of theory.

M.p. 98-99 ° C.

Example 11 [4- (4-Chloro-3-nitrophenylthio) phenyl] - (4-chloro-3-nitrophenyl) sulfoxide g 4-Chloro-3-nitro- Benzenesulfinyl chloride was added at 40 ° C over half an hour to a mixture of 28.2 g (0.21 mol) of aluminum chloride and 35 ml of benzene. The reaction mixture was stirred at 40 ° C for 2 hours and worked up as in Example 3.

such as phenyl (4-chloro-3-nitrophenyl) sulfoxide and 4- (4-chloro-3-nitrophenylthio) phenyl] - (4-chloro-3-nitrophenyl) - a mixture of sulfoxide is obtained which is separated by chromatography.

Yield: 30% of theory for the title compound.

144-146 ° C.

Example 12 (4-Chloro-3-nitrophenyl) - (4-fluorophenyl) sulfoxide

In each case, the procedure described in Example 5 is followed except that

Fluorobenzene was used in place of -715 toluene and the reaction temperature was 50 ° C instead of 35 ° C.

Yield 92% of theory.

Melting point: 84-85 ° C.

Example 13 (4-Chloro-3-nitro-phenyl) - (4-bromo-phenyl) -esulfoxide

All of the procedures described in Example 5 were followed except that bromobenzene was used in place of toluene.

Yield 89% of theory.

Melting point: 140-1 ° C.

Example 14

4 - [(4-chloro-3-nitrophenyl) sulfinyl] -4'-bromobiphenyl

All were carried out as in Example 5 except that 4-bromobiphenyl was used in place of toluene.

Yield 82% of theory.

Melting point: 173-5 ° C.

Example 15

4 [(4-chloro-3-nitrophenyl) -szulfmil] -4'-nitro-biphenyl

All were carried out as in Example 5 except that 4-nitrobiphenyl was used in place of toluene.

Yield 65% of theory.

Melting point: 220-2 ° C.

Example 16 (2-Chloro-5-nitrophenyl) - (4-fluorophenyl) -

sulfoxide g (0.1625 mol) of 2-chloro-5-nitrobenzenesulfonic acid (60 mL of dichloroethane and 36 mL of thionyl chloride) was refluxed for 1 hour and the dichloroethane thionyl chloride mixture was distilled under vacuum at 60 ° C. 28.2 g (0.21 mol) of aluminum chloride are added to the solution under ice-cooling at a temperature below 40 ° C, the mixture is stirred at 50 ° C for 2.5 hours and then poured into 150 ml of ice-water with cooling, the organic phase is added. the aqueous phase was extracted with 50 ml of benzene. The combined organic phases are freed of solvent in vacuo. 42.3 g of the title compound are obtained.

Yield 87% of theory.

Mp 155-8 ° C.

Example 17 (2-Chloro-5-nitrophenyl) (4-chlorophenyl) sulfoxide

All of the procedures described in Example 16 were followed except that chlorobenzene was used in place of fluorobenzene.

Yield 89% of theory.

M.p. 142-4 ° C.

Example 18 (2-Chloro-5-nitrophenyl) (4-methoxyphenyl) sulfoxide

All of the procedures described in Example 16 were repeated except that anisole was used in place of fluorobenzene and the reaction temperature was 25 ° C.

Yield 82% of theory.

Melting point: 172-3 ° C.

Example 19 (4-Ethoxy-3-nitrophenyl) phenylsulfoxide

Each was prepared in the same manner as in Example 7 except that 4-ethoxy-3-nitrobenzenesulfonyl chloride was used instead of 4-methoxy-3-nitrobenzenesulfonyl chloride.

Yield 71% of theory based on the sulfochloride.

Melting point: 119-121 ° C.

Example 20 (4-Chloro-3-nitrophenyl) (4-methoxyphenyl) sulfoxide

The procedure of Example 16 was followed except that starting material was 4-chloro-3-nitrobenzenesulfinic acid, instead of fluorobenzene, anisole was used and the reaction temperature was 25 ° C.

Yield 89% of theory.

Melting point: 125-6 ° C.

Claims (9)

PATENT CLAIMS A process for the preparation of a novel nitro-diaryl sulfoxide of the formula I in which R ¹ is halogen or C 1-4 alkoxy, R ² is hydrogen, halogen, C 1-4 alkyl, C 1-4 alkoxy. a group optionally substituted by a halogen atom or a nitro group, characterized in that an arylsulfonyl halide of formula (II) wherein R ¹ -817 are as defined in formula (I) and X ¹ is halogen is reduced with an alkali metal sulfite, the (III) arilszulfinátot formula - wherein R ¹ is of formula I képlet- 5 at each defined and M represents an alkali metal - treating with an acid the arylsulfinic acid of formula (IV), wherein R ¹ is as defined in formula (I), or the arylsulfinate of formula (III), wherein R ¹ and M are a halogenating agent, then the new (V) arylsulfinyl halide obtained - wherein corresponding R ¹ je- 15 Lentes (I) to formula defined and X ² represents a halogen atom with a Lewis acid metal halide catalyst formula (VI) with a benzene of formula derivative - wherein R ^{2 is} represented by the general formula (I) equation -. 2. A process according to claim 1, wherein the reduction comprises 1.1 to 4 moles of alkali metal sulfite per arylsulfonyl halide of formula II, wherein R ¹ and X ¹ are as defined in claim 1. used. The process according to claim 1 or 2, wherein the reduction of the arylsulfonyl halide of formula (II), wherein R ¹ and X ¹ are as defined in claim 1, is carried out between 20 ° C and 50 ° C. temperature. 4. A process according to any one of claims 1 to 3, wherein the reduction of the arylsulfonyl halide of formula (II), wherein R ¹ and X ¹ are as defined in claim ^1, is carried out in a ₄ basic weak medium. 5. A process according to claim 1 wherein the aryl sulfinate of formula III is treated with an excess of a strong mineral acid as the acid. 6. A process according to claim 1, wherein the arylsulfinyl halide of formula (V) wherein R ¹ and X ² are as defined in claim 1 is directly isolated without removal of excess halogenating agent. with a benzene derivative of formula (VI) wherein R ² is as defined in claim 1. The process according to claim 1 or 6, wherein the arylsulfinyl halide of formula (V), wherein R ¹ and X ² are as defined in claim 1, and the benzene derivative of formula (VI) in which R ² is as defined in claim 1, the Lewis acid used is 1.1 to 1.8 moles of aluminum chloride per mole of arylsulfonyl chloride. A process according to any one of claims 1, 6 or 7, wherein the arylsulfinyl halide of formula (V) wherein R ¹ and X ^{2 are as} defined in claim 1 is as defined in general formula (VI). with a benzene derivative of the formula wherein R ² is as defined in claim 1 at a temperature of from 20 ° C to 80 ° C. 9. A process for the preparation of a pharmaceutical composition comprising the nitro-diaryl sulfoxide of the formula I according to claim 1, wherein R ¹ is halogen or C 1 -C 4 alkoxy, R ² is hydrogen, halogen, (C1-C4) -alkyl, (C1-C4) -alkoxy, phenyl optionally substituted by halogen or nitro, mixed with excipients which are conventional in the pharmaceutical art and converted to a pharmaceutical composition.