GB2155469A - Nitrodiaryl sulfoxide derivatives - 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

SPECIFICATION Nitrodiaryl sulfoxide derivatives The invention relates to new nitrodiaryl sulfoxide derivatives, to a process for their preparation and to pharmaceutical and pesticidal compositions containing them as active ingredient. More particularly, the invention concerns new nitrodiaryl sulfoxide derivatives of the formula (I)

wherein R' is halogen or alkoxy having from 1 to 6 carbon atoms, R2 is hydrogen, halogen, alkyl having from 1 to 6 carbon atoms or alkoxy having from 1 to 6 carbon atoms, or phenyl or phenylthio each optionally substituted by one or more identical or different halogen(s) and/or nitro group(s).

According to another aspect of the invention there is provided a process for the preparation of the new compounds of formula (I) as defined above which comprises reacting an arylsulfinyl halide of the formula (V)

(in which R1 is as defined above and X2 is halogen) with a benzene derivative of the formula (VI),

wherein R2 is as defined above) in the presence of a metal halide catalyst of the Lewis acid type.

The arylsulfinyl halide of formula (V) may be obtained, for example, by reacting an arylsulfinate of formula (Ill) or an arylsulfinic acid of formula (IV)

(in which R' is as defined above and M is an alkali metal) with a halogenating agent. The arylsulfinic acid of formula (IV) may be obtained, if desired by treating an arylsulfinate of formula (Ill) as defined above with an acid.

The arylsulfinate of formula (III) may, for example, be obtained by reducing a sulfonyl halide of the formula (II)

wherein Ri is as defined above, and Xa is halogen) with an alkali metal sulfite.

The new compounds of the formula (I) exhibit pesticidal activity. They are of particular use as pharmaceuticals for use in human and veterinary therapy, e.g. as nematocides, taenicides, and preferably as anthelmintics. Thus they show e.g. acaricidal, fungicidal, antimicrobial, herbicidal and especially insecticidal activity.

The compounds of the formula (I) are further useful intermediates in the preparation of other new and known, biologically active aromatic sulfoxide derivatives, such as benzimidazole and substituted diamino sulfoxide derivaties having anthelmintic and fungicidal activity, e.g. Oxfendazole. They can be prepared from the compounds according to the invention by reaction with an amine derivative, subsequent reduction and coupling with a carbamic acid derivative.

Compounds of the formula (I) are new. In the hitherto known nitro-substituted diaryl sulfoxides the nitro group was attached to one of the phenyl rings in the ortho- or para-position relative to the sulfoxide group, and the other substituents were different from those in the compounds according to the invention as to their quality, number and position relative to the sulfoxide group; while the only known compound containing an o-nitro group was unsubstituted. The structurally related, known diaryl sulfoxides were generally prepared by a different procedure, i.e. oxidation of the corresponding diaryl sulfides [Ber. 41, 2836 (1908), J. Am. Chem. Soc. 1381(1948)].

In the formula (I) R1 and R2 as halogen may represent fluorine, chlorine, bromine or iodine, preferably chlorine; while as alkoxy having from 1 to 6 carbon atoms they may be any straight-chained or branched alkoxy group, e.g. methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, sec.-butoxy, isobutoxy, n-pentoxy, isopentoxy, n-hexyloxy, isohexyloxy, etc., preferably methoxy. In the definition of R2 the term "alkyl having from 1 to 6 carbon atoms" is used to refer to straight-chained or branched alkyl groups, e.g. methyl, ethyl, n-propyl, isopropyl, n-butyl, sec.-butyl, isobutyl, tert.-butyl, n-pentyl, isopentyl, n-hexyl, isohexyl, etc.

In the compounds of formula (III) M as an alkali metal preferably stands for potassium or sodium.

In the compounds of formulae (II) and (V) X1 and X2 as halogen represent fluorine, chlorine, bromine or iodine, preferably chlorine.

The intermediates of the formula (V) are also new compounds and both they and their preparation is within the scope of the present invention.

The reduction of the arylsulfonyl halides of the formula (II) with alkali metal sulfiftes is preferably carried out in an aqueous medium, using the alkali metal sulfite in a slight excess, preferably in an amount of 1.1 to 4 moles per mole of arylsulfonyl halide. The reduction is generally performed at a temperature of from 20 to 500 e.g. at 20 to 35"C, preferably 22 to 28"C. The reduction is preferably accomplished under mildly alkaline conditions, between pH 7 and 9, preferably 7.5 and 8.5, for example by adding to the reaction mixture an alkali metal bicarbonate, alkali metal carbonate or alkali metal hydroxide either simultaneously or alternatively, prior to the addition of the reducing agent.The alkali metal component of the above reactants is preferably identical with the alkali metal of the alkali metal sulfite used as reducing agent. The above alkaline agents serve also as acid binding agents. The alkali metal bicarbonates, carbonates or hydroxides can be used either in a solid form and/or in the form of their saturated aqueous solutions.

The acid treatment of the compounds of the formula (III) is preferably carried out with a strong mineral acid, must preferably concentrated aqueous hydrochloric acid, etc. The mineral acid is preferably used in excess. The arylsulfinic acid obtained after hydrolysis is very pure (has a purity of at least 98%) and stable, in contradistinction to the arylsulfinic acids prepared hitherto by different processes. Compounds of formula (IV) are obtained in a very high yield, which considerably exceeds the yield of the hitherto known processes [Houben-Weyl, 9, 307].

Both the arylsulfinates of formula (III) and the arylsulfinic acids of formula (IV) can be reacted with a halogenating agent, to yield the corresponding arylsulfinyl halide of the formula (V). As a hologenating agent an inorganic or organic halogenating agent can be used. Inorganic halogenating agents include for example the compounds of sulfur and phosphorus with halogen or with halogen and oxygen. Typical representatives of these compounds are thionyl chloride, phosphorus trichloride, phosgene, phosphorus pentachloride, phosphorus oxychloride, and a combination of phosphorus oxychloride and chlorine. Organic halogenating agents include organic acid halides, such as oxalyl chloride.The arylsulfinyl halides of the formula (V) are new compounds, which are considerably more stable than the differently substituted arylsulfinyl haLides known in the art.

In the reaction of the compounds of formula (V) with the compounds of formula (VI) as a metal halide catalyst of the Lewis acid type any catalyst conventionally used in Friedel-Crafts acylations, e.g. preferably aluminium trichloride, can be used. According to a preferred embodiment of the reaction compounds of the formula (V) are reacted with the compounds of the formula (VI) without isolation, directly after elimination of the halogenating agent. The metal halide catalyst of the Lewis acid type is preferably used in an amount of 1.1 to 1.8 moles per mole of the arylsulfinyl halide of formula (V). The reaction generally is carried out at 0 C to 80"C, preferably 25 C to 42 C.

The process according to the invention yields the new nitrodiaryl sulfoxides in a high purity (at least 98 %) with excellent yield (90 to 96 % relative to the corresponding arylsulfinic acid, and about 85 % relative to the corresponding arylsulfonyl halide). The process according to the invention can easily be carried out even on industrial scale.

The reaction mixtures can be processed by conventional techniques, for example extraction, filtration, evaporation, precipitation with water, elimination of the solvent or the excess of reactants, decantation, etc.

The compounds of the formula (I) can be subjected, if desired, to further purification, e.g. recrystallization. The solvents used for recrystallization are selected depending on the solubility and crystallization properties of the compound to be crystallized.

The active compounds of the formula (I) may be formulated for therapeutic purposes. The invention therefore relates also to pharmaceutical compositions comprising an active ingredient at least one compound of formula (I), in association with pharmaceutical carriers and/or excipients. Carriers conventional for this purpose and suitable for parenteral or enteral administraiton as well as other additives may be used. As carriers solid or liquid compounds, for example water, gelatine, lactose, starch, pectin, magne sium stearate, stearic acid, talc, vegetable oils, such as peanut oil, olive oil, etc. can be used. The compounds can be formulated as conventional pharmaceutical formulations, for example in a solid (globuiar and angular pills, dragés, e.g. hard gelatine capsules) or liquid (injectable oily or aqueous solutions or suspensions) form.The quantity of the solid carrier can be varied within wide ranges, but preferably it is between 25 mg. and 1 g. The compositions optionally contain also conventional pharmaceutical additives, such as preserving agents, wetting agents, salts for adjusting the osmotic pressure, buffers, flavouring and odouring substances.

The compositions according to the invention optionally contain the compounds for formula (I) in association with other known active ingredients. The unit doses are selected depending on the route of administration. The pharmaceutical compositions may be prepared by conventional techniques including sieving, mixing, granulation, pressing or dissolution of the active ingredients. The formulations obtained are then subjected to additional conventional treatments, such as sterilization.

For use as pesticides, the compounds of the formula (I) are formulated as conventional formulations, e.g. solutions, emulsions, soluble powders, suspensions, powder compositions, aerosol compositions, suspension and emulsion concentrates, powders for seed dressing.

Thus according to a further feature of the invention there are provided pesticidal compositions comprising, as active ingredient, at least one compound of formula (I) in association with one or more solid and/or liquid carriers.

The compounds may, for example be used to impregnate natural and synthetic materials, or be formulated as micro-capsules, using polymeric substances and materials suitable for coating seeds, or can be converted into formulations supplied with combustible filling, such as smoke patrons, boxes, spirals, and warm or cold fog compositions, which may be applied by ULV (ultra- low-volume) techniques.

The pesticidal compositions can be prepared in a manner known per se, for example by mixing the active ingredients with carriers, i.e. liquid solvents, liquified gases under pressure and/or solid carriers. If desired, also surfactants, emulsifying and/or dispersing and/or foaming agents can be added to the system. If water is used as a carrier, as a co-solvent organic solvents may also be employed.The liquid solvents generally include 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 the ethers and esters thereof; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; and strongly polar solvents such as dimethyl formamide, dimethyl sulfoxide and water. As liquified gaseous carriers may be used for example aerosol propellants such as halogenated hydrocarbons, butane, propane, nitrogen and carbon dioxide.As solid carriers for example natural fossil materials, e.g. kaolin, clay earth, talc, chalkstone, quartz, attapulgite, montmorillonite or diatomaceous earth, and synthetic fossil materials such as highly dispersed silicic acid, alumina and silicates may be employed. As carriers for granulates for example broken and fractionated natural rocks, e.g. calcite, marble, pumice, sepiolite, dolomite, and granulates of inorganic and organic materials, as well as granulates prepared from organic materials such as sawdust, coconut, shell, corn husk and tobacco stems can be used.As emulsifying agents and/or foaming agents non-ionic and anionic emulsifiers such as polyoxyethylene fatty acid ethers, polyoxyethylene fatty alcohol ethers, e.g. alkyiarylpolyglycol ether, alkylsulfonates, alkylsulfates, arylsulfonates and protein hyrdolysates, while as dispersing agents e.g. lignine, sulfite waste liquors and methyl cellulose may be employed.

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

The pesticidal compositions according to the invention may further contain various pigments such as inorganic pigments, e.g. iron oxide, titanium dioxide, ferrocyane blue and organic pigments, e.g. alizarine, azometal phthalocyanine pigments, as well as micronutrients, e.g. iron, manganese, boron, copper, cobalt, molybdenum and zinc salts.

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

The active ingredients may be applied in the form of concentrates and/or ready-to-use formulations prepared therefrom.

The active ingredient concentration of the ready-to- use formulations, optionally prepared in situ from a concentrate may vary within wide limits generally between 0.000 000 1 and 95% by weight, e.g. 0.1 to 95%, preferably 0.01 to 10% by weight.

The route of application will depend on the specific formulation used.

According to a further feature of the invention there is provided a method of exterminating or preventing or inhibiting infestation by pests which comprises administering to a locus infested with or susceptible to infestation by pests an effective amount of a compound of formula (I).

In particular there is provided a method of exterminating or preventing or inhibiting infestation by pests on a human or animal body which comprises externally administering to the human or animal body an effective amount of a compound of formula (I).

The invention is elucidated in detail by the aid of the following non-limiting Examples.

Example 1 Sodium 4-chloro-3-nitro-benzenesu Ifinate To a solution of 24 g. of sodium bicarbonate in 30 ml. of water 71.8 g. (0.57 moles) of solid, anhydrous sodium sulfite are added. To the homogenous solution a mixture of 58.4 g. (0.228 moles) of 4-chloro-3nitro- benzenesulfonyl chloride and 24 g. of sodium bicarbonate is uniformly added over 2 hours, at 23 to 25"C. When the addition is complete, the suspension is stirred at 23 to 25"C for 4 hours and subsequently, after addition of 200 ml. of toluene, at 35 "C for 15 minutes. It is then cooled to 23 to 25 "C and stirred. The product is filtered off and air dried.

56 g. of sodium 4-chloro-3-nitro-benzenesulfinate are obtained. According to the potassium permanganate analytical method the product contains 85 % of active substance and 15 % of water.

Yield: 90 % of theoretical Example 2 4-Chloro-3-nitro-benzenesu Ifinic acid The sodium salt prepared according to Example 1 is dissolved in 300 ml. of water at 40 "C and filtered at the same temperature. The filtrate is cooled to 10 to 15 "C, acidified with 100 ml. of concentrated aqueous hydrochloric acid solution under thorough stirring, cooled to 5 C, filtered and the product obtained is dried at a temperature not exceeding 40 "C.

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

Purity: 99 % Melting point: 10 to 103 "C.

Yield related to the sulfonyl chloride: 85 % of theoretical Example 3 Phenyl-(4-chloro-3-nitrophenyl su If oxide a) 36 g. (0.1625 moles) of 4-chioro-3-nitro-benzenesulfinic acid prepared according to Example 2, 75 ml.

of benzene and 15.1 ml. of thionyl chloride are admixed. The reaction mixture is boiled for one hour and distilled in vacuo at a temperature below 60 "C. To the residue two further 25-ml-portions of benzene are added and the solvent is eliminated each time. To the residue weighing about 40 g. (n24 = 1.6240), which is crude 4-chloro-3-nitro- benzenesulfinyl chlordij, 20 ml. of dichloroethane are added, followed by the addition of 28.2 g. (0.21 moles) aluminium chlorie under cooling, at a temperature below 40 "C. Thereafter 35 ml. of benzene are added to the mixture at 40 C within half an hour.The reaction mixture is stirred at 40 C for two hours, diluted with 50 ml. of benzene, poured onto a mixture of 100 g. of ice and 50 ml. of water, the organic phase is extracted with 50 ml. of benzene. The combined benzene phases are decoloured with 5 g. of charcoal, filtered and the solvent is eliminated from the filtrate in vacuo.

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

Melting point: 86 to 87 "C Purity: 98 % (according to high-pressure liquid chromatography) Yield: 96 % of theoretical b) There are admixed 36 g. (0.1625 moles) of 4-chloro-3- nitro-benzenesulfinic acid prepared according to Example 2, 20 ml. of dichloroethane, 13.5 ml. (22 g., 0.185 moles) of thionyl chloride and 0.1 ml. of triethyl amine. The sulfinic acid is gradually dissolved while gas evolution is observed. The reaction mixture is heated at 50 "C for one hour, cooled to 5 to 10 OC, and 28.2 g. (0.21 moles) of aluminium chloride are added to the solution, taking care that the temperature of the reaction mixture should not exceed 40 "C. Thereafter 35 ml. of benzene are added to the mixture at 40 "C, in half an hour.The reaction mixture is stirred at 40 "C for two hours, diluted with 50 ml. of benzene, and poured onto a mixture of 100 g. of ice and 50 ml. of water. The organic phase is separated, and the aqueous phase is extracted with 50 ml.

of benzene. The combined benzene phases are decoloured with 5 g. of activated carbon, filtered and from the filtrate the major part of benzene is eliminated by distillation in vacuo, whereupon a solid substance is precipitated. Thereafter, the remaining part of benzene is eliminated with methanol, under atmospheric pressure, such that the reaction mixture contains about 60 to 70 ml. of methanol. The solution is then allowed to cool slowly. At 40 to 50 C crystallization starts. When the product forms a thick crystal pulp, 100 ml. of water having a temperature of 40 to 50 "C are added to the reaction mixture at 40 to 50 "C, initially at a slow rate. The loose, finely dispersed suspension is cooled to 15 to 20 OC under vigorous stirring, filtered and dried.

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

Example 4 Phenyl-(4-chloro-3-nitrophenyl) sulfoxide 23 g. (0.08 moles) of 84.7 % sodium 4-chloro-3-nitro- benzenesulfinate prepared according to Example 1 are dissolved in 50 ml. of benzene. To the solution 9.2 ml. (0.112 moles) of phosphorus trichloride and 10 ml. of benzene are added at a temperature below 30 "C, under vigorous stirring, in about 1.5 hours.

The mixture is stirred for further 2.5 hours at 22 to 25 C, the benzene solution of the sulfinyl chloride derivative is decanted or filtered off by suction. From the solution obtained the solvent is eliminated in vacuo and distillation is repeated with two 20-ml portions of benzene. The pale-yellow oily sulfinyl chloride derivative (n24D = 1.6250) is diluted with 18 ml. of benzene, and is then added to the suspension of 11.34 g. (0.085 moles) of aluminium chloride in 18 ml. of benzene at a temperature below 1500. When the addition is complete, the reaction mixture is allowed to warm up to 40 "C, and it is stirred at this temperature for two hours. The reaction mixture is then poured onto 100 ml. of icy water.The separated aqueous phase is extracted with 25 ml. of benzene. The combined benzene phases are decoloured with activated carbon, filtered and the filtrate is evaporated in vacuo.

21 g. of the desired compound are obtained.

Melting point: 86 to 87 "C Yield: 95 % of theoretical Example 5 (4-Chloro-3-nitrophenyl )-4-methylphenyl sulfoxide To about 40 g. of benzene- and thienyl chloride-free 4-chloronitrobenzene sulfinyl chloride, prepared according to Example 3,100 ml. of toluene and subsequently 28.2 g. (0.21 moles) of aluminium chloride are added at 20 "C, under cooling. The reaction mixture is stirred at 35 C for 2.5 hours, and is further treated as described in Example 3.

42g. of the desired compound are obtained.

Melting point: 82 to 84 "C Yield: 87 % of theoretical Example 6 (4-Chloro-3-nitrophenyl )-4-chlorophenyl sulfoxide The procedure described in Example 5 is followed, except that instead of toluene chlorobenzene is used, and the reaction mixture is stirred at 50 "C for 4 hours. The title compound is obtained with a yield of 89 %.

Melting point: 110 to 112 "C Example 7 Phenyl-(4-methoxy-3-nitrophenyl) su Ifoxide 4-Methoxy-3-nitrobenzene sulfonyl chloride (melting point: 66 "C) is reduced with sodium sulfite as described in Example 1, and the sodium 4-methoxy-3-nitrobenzene sulfinate is further treated as described in Example 4.

The title compound is obtained with a yield of 88 %. Melting point: 135 to 137 "C Example 8 2-Chloro-5-nitrobenzene sulfinic acid 321 ml. (4.7 moles) of chlorosulfonic acid and 79 g. (0.5 moles) of 4-chloro-nitrobenzene are stirred at 130 "C for 6 hours. The reaction mixture is then cooled to a temperature below 10 C and is poured onto 750 ml. of icy water. The mixture is filtered at room temperature and the substance collected on the filter is washed acid-free with about 2 litres of water.The crude 2-chloro-5-nitrobenzene sulfonyl chloride obtained is subjected to the subsequent reaction steps without purification. 118 g. (0.935 moles) of anhydrous sodium sulfite and 20 g. of sodium bicarbonate are dissolved in 250 ml. of water, and to the solution obtained a mixture of the crude 2-chloro-5-nitrobenzene sulfonyl chloride and 20 g. of sodium bicarbonate is added at a temperature of 23 to 25 "C, over one hour. The reaction mixture is stirred for two hours at a temperature of 23 to 25 "C, and, after the addition of 200 ml. of toluene, for further 15 minutes. The mixture is stirred at 25 "C and the substance filtered off is washed with 100 ml. of toluene.

The sodium 2-chloro-5-nitrobenzene sulfinate obtained is dissolved in 400 ml. of water at 40 "C, and the solution is admixed with 200 ml. of toluene. The insoluble part is filtered off and the toluene phase is separated from the filtrate. The aqueous phase is cooled to 10 C, acidified with 100 ml. of concentrated aqueous hydrochloric acid solution and the precipitated crystais are stirred, filtered off at 10 "C and dried.

61 g. of 2-chloro-5-nitrobenzene sulfinic acid are obtained. Yield: 55% of theoretical relative to 4-chloronitrobenzene.

Melting point: 128 to 130 C Purity: 98 % (according to potassium permanganate analytical method) Example 9 Phenyl-(2-chloro-5-nitrophenyl) sulfoxide 26 g. (0.1625 moles) of 2-chloro-5-nitrobenzene sulfinic acid are admixed with 60 ml. of benzene and 36 ml. of thionyl chloride. The reaction mixture is boiled for one hour. Thereafter the procedure described in Example 3 is followed, except that instead of benzene dichloroethane is used for dilution and extraction.

40 g. of phenyl-(2-chlorn-'5-nitrnphenyl) sulfoxide are obtained as a white microcrystalline substance.

Melting point: 150 to 152 "C.

Purity: 97 % (according to high-pressure liquid chromatography) Yield: 85 % of theoretical Example 10 4-(4-Chloro-3-nitrophenylsu Ifinyl)-biphenyl The procedure described in Example 5 is followed except that instead of toluene biphenyl is employed.

The desired compound is obtained with a yield of 90 %.

Melting point: 98 to 99 "C Example 11 4-(4-Chloro-3-nitrophenylthio)-phenyl-(4-chloro-3-nitrophenyl) sulfoxide 36 g. (0.1625 moles) of 4-chloro-3-nitrobenzene sulfinic acid is prepared according to Example 2, 35 ml.

of benzene, 10.5 ml. (0.143 moles) of thionyl chloride and 0.1 g. of anhydrous ferric chloride are boiled for one hour. To the solution 28.2 g. (0.21 moles) of aluminium chloride are added at a temperature below 40 "C. The reaction mixture is stirred at 40 "C for 2 hours, thereafter the procedure described in Example 3 is followed. The oily product obtained is dissolved in hot acetone and to this solution a small amount of aqueous methanol is added. Thereafter the separated oil is dissolved in hot acetone and treated again with aqueous methanol. The oily portion is separated. Upon addition of acetone the desired compound is obtained in a crystalline form.

11.4 g. of the title compound are obtained.

Yield: 30 % of theoretical Melting point: 144 to 146 "C Example 12 (4-Chloro-3-nitrophenyl)-4-methoxyphenyl su Ifoxide The reaction mixture containing 4-chloro-3-nitrobenzene sulfinyl chloride prepared as described in Example 3, variant b) is released from thionyl chloride by distillation in vacuo. To the residue 50 ml. of dichloroethane and 21.6 g. of anisole are added, the mixture is cooled to -5 "C and 33.4 g. of aluminium chloride are added portionwise, taking care that the temperature of the mixture should not exceed 20 "C.

The reaction mixture is then kept at 20 "C for 4 hours, poured onto 300 ml. of icy water, extracted with dichloroethane and the solvent is eliminated from the organic solvent phase in vacuo.

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

Yield: 92 % of theoretical Melting point: 124 to 126 "C Example 13 (4-Chloro-3-nitrophenyl)-4-fluorophenyl sulfoxide To about 40 g. of crude, benzene- and thionyl chloride-free 4-chloronitrobenzene sulfinyl chloride, prepared according to any variant of Example 3,90 ml. of fluorobenzene are added, followed by addition of 33.6 g. of aluminium chloride under cooling. The reaction mixture is then stirred at 55 "C for 5 hours and is further treated as described in Example 3, except that the reaction mixture is not diluted with benzene.

42 g. of the desired compound are obtained.

Yield: 86 % of theoretical Melting point: 84 to 85 "C Example 14 (4-Bromophenyl)-(4-chloro-3-nitrophenyl) sulfoxide To about 40 g. of crude 4-chloro-3-nitrobenzene sulfinyl chloride, prepared according to any variant of Example 3,100 ml. of bromobenzene are added. Under cooling 33.6 g. of aluminium chloride are added to the mixture, which is then stirred at 50 "C for 3 hours and is further treated as described in Example 3, except that benzene is added to the reaction mixture after pouring onto water, and the excess of bromobenzene is eliminated from the reaction mixture by distillation at 60 to 70 "C, under a pressure of 30 to 40 mmHg.

54.5 g. of the desired compound are obtained.

Yield: 93 % of theoretical Melting point: 138 to 140 "C Example 15 4-Chlorophenyl-(2-chloro-5-nitrophenyl) sulfoxide 36 g. (0.1625 moles) of 2-chloro-5-nitrobenzene sulfinic acid prepared according to Example 8 are converted into 2-chloro-5-nitrobenzene sulfinyl chloride as described in Example 3. It is then released from benzene and thionyl chloride, diluted with 100 ml. of chlorobenzene, and to the mixture 28.2 g. of aluminium chloride are added under stirring. The reaction mixture is then sti;;ed at 55 "C for 5 hours and is further treated as described in Example 3, except that the dilution with benzene is carried out only after pouring onto water.

44 g. of the desired compound are obtained.

Yield: 86 % of theoretical Melting point: 142 to 144 "C Example 16 (4-Ethoxy-3-nitrophenyl)-phenyl sulfoxide The procedure described in Example 7 is followed, except that 4-ethoxy-3-nitrobenzene sulfonyl chloride is used as a starting material and from this sodium 4-ethoxy-3-nitrobenzene sulfinate is prepared as described in Example 1, with a yield of 70 % which is then treated further as described in Example 4.

The desired compound is obtained with a yield of 86 %.

Melting point: 119 to 121 "C Example 17 1 -(4-Bromophenyl)-4-(4-chloro-3-nitrophenylsulfinyl)-benzene The procedure described in Example 5 is followed, except that instead of toluene 4-bromo-biphenyl is used. The desired compound is obtained with a yield of 80 %.

Melting point: 173 to 175 "C Example 18 (4-Chloro-3-nitrophenyl )-4-methylthiophenyl sulfoxide The procedure described in Example 5 is followed, except that instead of toluene thioanisole is used.

Example 19 1 -(4-N itrophenyl) 4-(4-ch loro-3-n itrophenylsulfinyl) benzene The procedure described in Example 5 is followed, except that toluene is replaced by 4-nitro-biphenyl.

The title compound is obtained with a yield of 50 %.

Melting point: 220 to 222 "C

Claims (42)

1. Nitrodiaryl sulfoxides of the formula (I),

wherein RI is halogen or alkoxy having from 1 to 6 carbon atoms, R2 is hydrogen, halogen, alkyl having from 1 to 6 carbon atoms or alkoxy having from 1 to 6 carbon atoms, or phenyl or phenylthio each optionally substituted by one or more identical or different halogen(s) and/or nitro group(s).

2. Phenyl-(4-chloro-3-n itrophenyl) sulfoxide.

3. (4-Chloro-3-nitrophenyl)-4-methylphenyl sulfoxide.

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

5. Phenyl-(4-methoxy-3-nitrophenyl) sulfoxide.

6. Phenyl-(2-chloro-5-nitrophenyl) sulfoxide.

7. (4-Chloro-3-nitrophenyl)-4-biphenylyl sulfoxide.

8. (4-Ch loro-3-n itrophenyl )-4-methoxyphenyl sulfoxide.

9. (4-Chloro-3-nitrophenyl)-4-fluorophenyl sulfoxide.

10. 4-Bromophenyl-(4-chloro-3-nitrophenyl) sulfoxide.

11. 4-Chlorophenyl-(2-chloro-5-nitrophenyl) sulfoxide.

12. (4-Ethoxy-3-nitrophenyl )-phenyl sulfoxide.

13. 1 -(4-Bromophenyl )-4-(4-chloro-3-nitrophenylsulfinyl) benzene.

14. 1 iron -(4-Nitrophenyl )-4-(4-chlorn-3-nitrnphenylsu Ifinyl) benzene,

15. 4-[(4-Ch loro-3-nitrophenylthio)-phenylj-(4-chloro-3-nitrophenyl) sulfoxide.

16. Compounds according to claim 1 for use as pesticides.

17. Pharmaceutical compositions comprising as active ingredient, at least one compound according to claim 1, in association with a pharmaceutical carrier and/or excipient.

18. Pesticidal compositions comprising, as active ingredient, at least one compound according to claim 1 in association with one or more solid and/or liquid carriers.

19. Compositions according to claim 18 containing from 0.01 to 10% by weight of active ingredient.

20. Compositions according to claim 17 or claim 18 substantially as herein described.

21. A process for the preparation of compounds according to claim 1 which comprises reacting an arvlsulfinvl halide of formula (V)

(wherein RI is as defined in claim 1 and X2 is halogen) with a benzene derivative of formula (VI),

(wherein R2 is as defined in claim 1) in the presence of a metal halide catalyst of the Lewis acid type.

22. A process according to claim 21 wherein the catalyst is aluminium chloride used in an amount of from 1.1 to 1.8 moles per mole of arylsulfinyl halide of formula (V).

23. A process according to claim 21 or claim 22 wherein the reaction is carried out at temperatures of from 25 to 420C.

24. A process according to any one of claims 21 to 23 wherein the arylsulfinyl halide of formula (V) is obtained by reaction of an arylsulfinate of formula (III) or an arylsulfinic acid of formula (IV)

(wherein R1 is as defined in claim 1 and M is an alkali metal) with a halogenating agent.

25. A process according to claim 24 wherein, after reaction of the arylsulfinate of formula (III) or the arylsulfinic acid of formula (IV) with the halogenating agent, excess halogenating agent is eliminated and the arylsulfinic acid of formula (V) obtained is reacted with the benzene derivative of formula (Vl) without isolation.

26. A process according to claim 24 or claim 25 wherein an arylsulfinic acid of formula (IV) is reacted with the halogenating agent, the said acid being obtained by treating an arylsulfinate of formula (III) as defined in claim 24 with an acid.

27. A process according to claim 26 wherein the arylsulfinate of formula (III) is treated with an excess of a strong mineral acid.

28. A process according to any one of claims 24 to 27 wherein the arylsulfinate of formula (III) is obtained by reducing an arylsulfonyl halide of formula (II)

(wherein R1 is as defined in claim 1 and Xa is halogen) with an alkali metal sulfite.

29. A process according to claim 28 wherein reduction is effected using 1.1 to 4 moles of alkali metal sulfite per mole of arylsulfinyl halide of formula (II).

30. A process according to claim 28 or claim 29 wherein the reduction is carried out at temperatures of from 22 to 28"C.

31. A process according to any one of claims 28 to 30 wherein the reduction is carried out under mildly alkaline conditions.

32. A process for the preparation of compounds according to claim 1 substantially as herein described.

33. A process for the preparation of compounds according to claim 1 substantially as herein described with reference to the Examples.

34. Compounds according to claim 1 whenever prepared by a process according to any one of claims 21 to 33.

35. The use of a compound according to claim 1 for the manufacture of a pesticide.

36. A method of exterminating or preventing or inhibiting infestation by pests which comprises administering to a locus infested with or susceptible to infestation by pests an effective amount of a compound according to claim 1.

37. A method of exterminating or preventing or inhibiting infestation by pests on a human or animal body which comprises externally administering to the human or animal body an effective amount of a compound according to claim 1.

38. Compounds of formula (V) as defined in claim 21.

39. A process for the preparation of compounds according to claim 38 as claimed in any one of claims 24 to 31.

40. A process for the preparation of compounds according to claim 38 substantially as herein described.

41. Compounds according to claim 38 whenever prepared by a process according to claim 39 or claim 40.

42. Each and every novel method, process, compound and composition herein disclosed.