Certain dioxomorpholines and processes for their preparation are already known (cf. for example Liebigs Ann. Chem. 1952 (1982), Makromol. Chem. , Rapid Commun., 6 (1985), 607; Tetrahedron, 37 (1981), 2797; WO 9403441A1 ; ), although nothing has been disclosed to date concerning the use of these compounds against endoparasites.

WO 96/15 121 discloses dioxomorpholines which are suitable for combating endoparasites. The compounds described do not, however, contain a sulphonamide side chain.

1. Compounds of the formula (I) in which Rl represents hydrogen, halogen, nitro, cyano, alkyl, aryl, trialkylsilyl, alkoxy or -S (O) rR, which are optionally substituted, R2 represents hydrogen, halogen, nitro, cyano, alkyl, aryl, trialkylsilyl, alkoxy or -S (O) rR, which are optionally substituted,

R3 represents optionally substituted alkyl, R4 represents optionally substituted alkyl or R3 and R4 together represent a spirocyclic radical which is optionally substituted, RS represents hydrogen, alkyl, arylalkyl or substituted phenyl, which is optionally substituted, r represents 0,1 or 2, R represents optionally substituted alkyl, m represents 0,1, 2,3, 4 or 5, n represents 0,1, 2,3, 4 or 5, and optical isomers and racemates thereof.

The compounds of the formula (I) can, depending on the type and number of substituents, optionally be present in the form of geometrical and/or optical isomers or regioisomers or mixtures of isomers of various composition. Both the pure isomers and the isomeric mixtures are claimed according to the invention.

It has also been found that dioxomorpholines of the formula (I) can be prepared by reacting 8-hydroxycarboxylic acids of the formula (II)

in which R1, R2, R3, R4, R5, m and n have the abovementioned meaning, with a dehydrating agent in an intramolecular lactonization reaction.

The dioxomorpholines according to the invention are generally defined by the formula (I).

Rl preferably represents hydrogen, bromine, chlorine, fluorine, cyano, nitro, tri- (Cl-C6-alkyl) silyl, Cl-C6-alkyl, Cl-C6-halogenoalkyl, Cl-C6-alkoxy, C1-C6- halogenoalkoxy, -S (O) rR or phenyl, wherein the phenyl group optionally contains one or more identical or different W1 substituents.

R2 preferably represents hydrogen, bromine, chlorine, fluorine, cyano, nitro, tri- (C1-C6-alkyl) silyl, Cl-C6-alkyl, Cl-C6-halogenoalkyl, Ci-Ce-alkoxy, C1-C6- halogenoalkoxy, -S (O) rR or phenyl, wherein the phenyl group optionally contains one or more identical or different Wl substituents.

R3 preferably represents Cl-C6-alkyl which is optionally substituted by Cl-C6- halogenoalkyl or Cl-C6-alkoxy.

R4 preferably represents Ci-C6-alkyl which is optionally substituted by Cl-C6- halogenoalkyl or Cl-C6-alkoxy.

R3 and R4 can also preferably together represent C3-Cs-alkylene,- (CH2)-O- (CH2)- or - (CH2) 2-0- (CH2) 2-, which can in each case optionally be mono-or polysubstituted by fluorine, chlorine, bromine, C1-C6-alkyl or C1-C6-alkoxy, thereby forming a spirocyclic radical.

R5 preferably represents hydrogen, C1-C6-alkyl or benzyl or phenyl, wherein benzyl and phenyl optionally contain one or more identical or different W1 substituents.

R preferably represents Cl-C6-alkyl or C1-C6-halogenoalkyl. m preferably represents 0, 1, 2,3 or 4. n preferably represents 0,1, 2,3 or 4. r preferably represents 0,1 or 2.

W1 preferably represents hydrogen, bromine, chlorine, fluorine, Cl-C6-alkyl, Cl- C6-halogenoalkyl, Cl-C6-alkoxy, C1-C6-halogenoalkoxy, -S(O)rR, cyano or nitro.

RI particularly preferably represents hydrogen, bromine, chlorine, fluorine, cyano, tri-(C1-C4-alkyl) silyl, Cl-C4-alkyl, C1-C4-halogenalkyl, Cl-C4-alkoxy, Cl-C4-halogenoalkoxy,-S (O) rR or phenyl, wherein the phenyl group optionally contains one or more identical or different Wl substituents.

R2 particularly preferably represents hydrogen, bromine, chlorine, fluorine, cyano, tri- (Cl-C4-alkyl) silyl, Cl-C4-alkyl, Cl-C4-halogenoalkyl, Cl-C4- alkoxy, C1-C4-halogenoalkoxy, -S (O) rR or phenyl, wherein the phenyl group optionally contains one or more identical or different W1 substituents.

R3 particularly preferably represents Cl-C4-alkyl which is optionally substituted by Cl-C4-halogenoalkyl or Cl-C4-alkoxy.

R4 particularly preferably represents Cl-C4-alkyl which is optionally substituted by Cl-C4-halogenoalkyl or Cl-C4-alkoxy.

R3 and R4 can also particularly preferably together represent C3-C6-alkylene,- (CH2)- 0- (CH2)- or- (CH2) 2-0- (CH2) 2-, which can in each case optionally be mono- or polysubstituted by fluorine, chlorine, bromine, Cl-C4-alkyl or Cl-C4- alkoxy, thereby forming a spirocyclic radical.

RS particularly preferably represents hydrogen, Cl-C4-alkyl or benzyl or phenyl, wherein benzyl and phenyl optionally contain one or more identical or different Wl substituents.

R particularly preferably represents Cl-C4-alkyl or Cl-C4-halogenoalkyl. m particularly preferably represents 0,1, 2 or 3. n particularly preferably represents 0,1, 2 or 3. r particularly preferably represents 0,1 and 2.

Wl particularly preferably represents hydrogen, bromine, chlorine, fluorine, Cl- C4-alkyl, Cl-C4-halogenoalkyl, Cl-C4-alkoxy, Cl-C4-halogenoalkoxy, - S (O) rR, cyano or nitro.

Rl very particularly preferably represents hydrogen, bromine, chlorine, fluorine, cyano, nitro, trimethylsilyl, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, s-butoxy, t-butoxy, trifluoromethoxy,

trifluoroethoxy,-SCH3,-SC2H5,-SOCH3,-SOC2H5,-S02CH3,-S02C2H5 or phenyl, wherein the phenyl group optionally contains one or more identical or different Wl substituents.

R2 very particularly preferably represents hydrogen, bromine, chlorine, fluorine, cyano, nitro, trimethylsilyl, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, s-butoxy, t-butoxy, trifluoromethoxy, trifluoroethoxy,-SCH3,-SC2H5,-SOCH3,-SOC2H5,-S02CH3,-S02C2H5 or phenyl, wherein the phenyl group optionally contains one or more identical or different W1 substituents.

R3 very particularly preferably represents methyl, ethyl, n-propyl, i-propyl, n- butyl, i-butyl, s-butyl, t-butyl, trifluoromethyl, trifluoroethyl,-CH2CH20CH3 or-CH2CH20CH2CH3.

R4 very particularly preferably represents methyl, ethyl, n-propyl, i-propyl, n- butyl, i-butyl, s-butyl, t-butyl, trifluoromethyl, trifluoroethyl,-CH2CH2OCH3 or-CH2CH20CH2CH3.

R3 and R4 can also very particularly preferably together represent cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, methylcyclohexyl, methoxycyclohexyl, ethoxycyclohexyl,- (CH2) 2-0- (CH2) 2- or- (CH2) 2-0-CH (CH3) CH2-, thereby forming a spirocyclic radical.

R5 very particularly preferably represents hydrogen, methyl, ethyl, n-propyl, i- propyl, n-butyl, i-butyl, s-butyl or t-butyl, or benzyl or phenyl, wherein benzyl and phenyl optionally contain one or more identical or different Wl substituents.

m very particularly preferably represents 0,1 or 2. n very particularly preferably represents 0,1 or 2.

W1 very particularly preferably represents hydrogen, bromine, chlorine, fluorine, cyano, nitro, trimethylsilyl, methyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, trifluoromethyl, trifluoroethyl, methoxy, ethoxy, n-propoxy, i-propoxy, n-butoxy, i-butoxy, s-butoxy, t-butoxy, trifluoromethoxy, trifluoroethoxy,-SCH3,-SC2H5-SOCH3,-SOC2H5,-SO2CH3,-SO2C2H5, cyano or nitro.

To prepare the compounds of the formula (I), the compounds of the formula (II) are subjected to intramolecular lactonization under the action of a dehydrating agent (or a coupling reagent) and optionally in the presence of a solvent and optionally a base according to the following scheme: Preferred dehydrating agents are acids, such as for example 4-toluenesulphonic acid, methanesulphonic acid or trifluoromethanesulphonic acid. They can be used in catalytic or excess quantities.

Hydrocarbons, such as for example toluene, or halogen-containing solvents, such as for example 1, 2-dichloroethane, are preferably used as solvents. The reaction temperatures are preferably 20 to 200°C, and particularly preferably 60 to 120°C (cf.

G. Kardassis et al, Tetrahedron 1998,54, 3479).

So-called peptide coupling reagents, such as for example isobutyl chloroformate, can also be used. Reagents such as CDI, DCC, EDCI, BOP, BOP-C1 and DEAD/Ph3P are also suitable.

Tertiary amines, such as for example N-methylmorpholine, are preferably used as auxiliary bases. Preferred diluents are halogen-containing solvents, such as for example dichloromethane. THF, DMF and CH3CN can also be used. The reaction temperatures are preferably minus 30 to plus 60°C, and particularly preferably minus 20 to plus 40°C.

Compounds of the formula (II) are prepared by the hydrolysis of esters of the formula (III) according to the following scheme: (il) Alkali metal hydroxides, such as for example sodium hydroxide, are preferred for the hydrolysis. Preferred dilluents are alcohols, such as for example methanol, or dioxan or water or mixtures thereof. The reaction temperatures are preferably minus 10 to plus 60°C, and particularly preferably 0 to plus 30°C.

Compounds of the formula (III) can be prepared by reacting-lactams of the formula (IV) with a-amino esters of the formula (V) according to the following scheme:

(IV) (V) (lll) a-Amino esters of the formula (V) are known or can be prepared by known methods (see in this regard, for example, Houben-Weyl, Methoden der organischen Chemie/Methods of Organic Chemistry). They can be used as the free base or as the hydrochloride. The reaction is usually carried out in the presence of a base and in the presence of a diluent. Suitable bases are alkali metal carbonates or alkali metal hydrogen carbonates and alkali metal hydroxides and tertiary amines, the latter being preferred; an example which may be mentioned is n-methylmorpholine. Suitable solvents are hydrocarbons, THF, CH3CN, dioxan or halogenated hydrocarbons, the latter being preferred; dichloromethane may be mentioned as an example. The preferred reaction temperatures are 0 to plus 120°C, particularly preferably 20 to plus 60°C (cf. I. Ojima et al, J. Org. Chem. 1994,59, 1249; C. Palomo et al, J. Chem.

Soc. Chem. Comm. 1994,1957.) (3-Lactams of the formula (IV) can be prepared by known methods (cf. V. Sriraj an et al, Tetrahedron Asymmetry 1996,7, 2733. ), namely by [2 + 2]-cycloaddition of N- tosyl imines of the formula (VI) and acetoxyketene. Acetoxyketene is prepared in situ by the base-induced dehydrodehalogenation of acetoxyacetyl chloride according to the following scheme:

Tertiary amines, such as for example triethylamine, are preferably used as bases. Halogen-containing solvents, such as for example dichloromethane, are preferably used. The reaction temperatures are preferably minus 40 to plus 60°C, and particularly preferably minus 20 to plus 30°C.

Acetoxyacetyl chloride is known and is commercially available.

The tosyl imines of the formula (VI) are in part known or they can be prepared by known methods by the condensation of aryl sulphonamides of the formula (VII) with benzaldehydes or benzaldehyde acetals of the formula (VIII) according to the following scheme (cf. V. Srirajan et al, Tetrahedron Asymmetry 1996,7, 2733. ): The compounds of the formulae (VII) and (VIII) are in part commercially available or they can be prepared by known methods (see for example Houben-Weyl, Methoden der organischen Chemie/Methods of Organic Chemistry).

The active compounds have a favourable level of toxicity to warm-blooded animals and are suitable for combating pathogenic endoparasites which occur in humans and in the keeping and breeding of animals, in livestock, zoo animals, laboratory animals, animals for experiments and pet animals. They are active against all or individual stages of development of the pests and against resistant and normally sensitive species.

The aim of combating pathogenic endoparasites is to reduce disease, deaths and reductions in yield (e. g. in the production of meat, milk, wool, hides, eggs, honey and the like) and the use of the active compounds thus makes the keeping of animals more economic and simple. The pathogenic endoparasites include cestodes, trematodes, nematodes and Acanthocephala, and in particular: From the order of the Pseudophyllidea, for example: Diphyllobothrium spp. , Spirometra spp. , Schistocephalus spp. , Ligula spp. , Bothridium spp. and Diphlogonoporus spp..

From the order of the Cyclophyllidea, for example: Mesocestoides spp., Anoplocephala spp. , Paranoplocephala spp., Moniezia spp.,'Thysanosomsa spp. , Thysaniezia spp. , Avitellina spp. , Stilesia spp. , Cittotaenia spp. , Andyra spp. , Bertiella spp. , Taenia spp. , Echinococcus spp. , Hydatigera spp. , Davainea spp. , Raillietina spp., Hymenolepis spp. , Echinolepis spp. , Echinocotyle spp. , Diorchis spp. , Dipylidium spp., Joyeuxiella spp. and Diplopylidium spp..

From the subclass of the Monogenea, for example: Gyrodactylus spp., Dactylogyrus spp. and Polystoma spp..

From the subclass of the Digenea, for example: Diplostomum spp., <BR> <BR> <BR> <BR> Posthodiplostomum spp. , Schistosoma spp. ; Trichobilharzia spp. , Ornithobilharzia spp., Austrobilharzia spp. , Gigantobilharzia spp. , Leucochloridium spp., Brachylaima spp. , Echinostoma spp. , Echinoparyphium spp. , Echinochasmus spp. , Hypoderaeum spp. , Fasciola spp. , Fasciolides spp. , Fasciolopsis spp. , Cyclocoelum spp., Typhlocoelum spp. , Paramphistomum spp., Calicophoron spp. , Cotylophoron spp., Gigantocotyle spp. , Fischoederius spp. , Gastrothylacus spp. , Notocotylus spp.,

Catatropis spp. , Plagiorchis spp., Prosthogonimus spp. , Dicrocoelium spp. , Eurytrema <BR> <BR> <BR> <BR> <BR> spp. , Troglotrema spp. , Paragonimus. spp. , Collyriclum spp., Nanophyetus spp. , Opisthorchis spp. , Clonorchis spp. , Metorchis spp. , Heterophyes spp. and Metagonismus spp..

From the order of the Enoplida, for example: Trichuris spp. , Capillaria spp. , Tri- chomosoides spp. , Trichinella spp..

From the order of the Rhabditia, for example: Micronema spp. and Strongyloides spp..

From the order of the Strongylida, for example: Stronylus spp. , Triodontophorus spp. , Oesophagodontus spp. , Trichonema spp. , Gyalocephalus spp., Cylindropharynx spp. , Poteriostomum spp. , Cyclococercus spp. , Cylicostephanus spp. , Oesophagostomum spp. , Chabertia spp., Stephanurus spp. , Ancylostoma spp., Uncinaria spp. , Bunostomum spp. , Globocephalus spp., Syngamus spp. , Cyathostoma spp., Metastrongylus spp. , Dictyocaulus spp. , Muellerius spp., Protostrongylus spp. , Neo- strongylus spp. , Cystocaulus spp., Pneumostrongylus spp. , Spicocaulus spp., <BR> <BR> <BR> <BR> <BR> Elaphostrongylus spp. , Parelaphostrongylus spp. , Crenosoma spp. , Paracrenosoma<BR> <BR> <BR> <BR> <BR> <BR> <BR> <BR> spp. , Angiostrongylus spp. , Aelurostrongylus spp. , Filaroides spp., Parafilaroides spp. , Trichostrongylus spp. , Haemonchus spp. , Ostertagia spp. , Marshallagia spp. , Cooperia <BR> <BR> <BR> <BR> <BR> spp. , Nematodirus spp. , Hyostrongylus spp. , Obeliscoides spp. , Amidostomum spp. and Ollulanus spp..

From the order of the Oxyurida, for example: Oxyuris spp. , Enterobius spp., Passalurus spp. , Syphacia spp. , Aspiculuris spp. and Heterakis spp..

From the order of the Ascaridia, for example: Ascaris spp. , Toxascaris spp. , Toxocara spp. , Parascaris spp., Anisais spp. and Ascaridia spp..

From the order of the Spirurida, for example.: Gnathostoma spp. , Physaloptera spp., Thelazia spp. , Gongylonema spp. , Habronema spp., Parabronema spp. , Draschia spp. and Dracunculus spp..

From the order of the Filariida, for example: Stephanofilaria spp., Parafilaria spp. , Setaria spp. , Loa spp., Dirofilaria spp., Litomosoides spp. , Brugia spp. , Wuchereria spp. and Onchocerca spp..

From the order of the Gigantorhynchida, for example Filicollis spp., Moniliformis spp. , Macracanthorhynchus spp. and Prosthenorchis spp..

Livestock and breeding animals include mammals, such as for example cattle, horses, sheep, pigs, goats, camels, water buffalo, donkeys, rabbits, fallow deer and reindeer, fur-bearing animals such as, for example, mink, chinchillas and racoons, birds, such as for example chickens, geese, turkeys and ducks, fresh water and salt water fish, such as for example trout, carp and eels, reptiles and insects, such as for example the honey bee and the silkworm.

Laboratory and test animals include mice, rats, guinea pigs, golden hamsters, dogs and cats.

Pet animals include dogs and cats.

The compounds can be used both prophylactically and therapeutically.

The active compounds are used directly or in the form of suitable formulations, enterally, parenterally, dermally, nasally, by treatment of the environment or with the aid of shaped articles containing the active compound, such as for example strips, plates, tapes, collars, ear tags, limb bands or marking devices.

The enteral administration of the active compounds is effected for example orally in the form of powders, tablets, capsules, potions, granules, solutions suitable for oral

administration, suspensions and emulsions, boli, medicated feed or dnnking water. Dermal application is effected for example by dipping, spraying or pouring-on or spotting-on. Parenteral administration is effected for example by (intramuscular, subcutaneous, intravenous or intraperitoneal) injection or by means of implants.

Suitable formulations are: solutions such as injection solutions, oral solutions, concentrates for oral administration after dilution, solutions for use on the skin or in body cavities, pour-on formulations or gels ; emulsions and suspensions for oral or dermal administration and for injection ; semi- solid formulations; formulations in which the active compound is incorporated in an ointment base or in an oil-in-water or water-in-oil emulsion base; solid formulations such as powders, premixes or concentrates, granules, pellets, tablets, boli, capsules; aerosols and inhalation products and shaped articles containing active compounds.

Injection solutions are administered intravenously, intramuscularly and subcutaneously.

Injection solutions are prepared by dissolving the active compound in a suitable solvent and possibly adding additives such as solubilizers, acids, bases, buffer salts, antioxidants and preservatives. The solutions are subjected to sterile filtration and placed in containers.

Solvents which may be mentioned are: physiologically compatible solvents such as water, alcohols such as ethanol, butanol, benzyl alcohol, glycerol, propylene glycol, polyethylene glycols, N-methylpyrrolidone and mixtures thereof.

If appropriate, the active compounds can also be dissolved in physiologically compatible vegetable or synthetic oils suitable for injection.

Solubilizers which may be mentioned are: solvents which promote the dissolution of the active compoiund in the main solvent or which prevent its precipitation. Examples are polyvinyl pyrrolidone, polyoxyethylated castor oil and polyoxyethylated sorbitan esters.

Preservatives are: benzyl alcohol, trichlorobutanol, p-hydroxybenzoates and n-butanol.

Oral solutions are administered directly. Concentrates are administered orally after prior dilution to the use concentration. Oral solutions and concentrates are prepared as described above for the injection solutions, although sterile conditions can be dispensed with.

Solutions for use on the skin are applied in drops, spread on, rubbed in, misted on or sprayed on. These solutions are prepared as described above for the injection solutions.

It may be advantageous to add thickeners during the preparation. Thickeners are: inorganic thickeners such as bentonites, colloidal silica, aluminium monostearate, organic thickeners such as cellulose derivatives, polyvinyl alcohols and copolymers, acrylates and methacrylates thereof.

Gels are applied or spread onto the skin or introduced into body cavities. Gels are prepared by adding to solutions which have been prepared as described for the injection solutions, such a quantity of thickener that a clear mass with an ointment-like consistency is formed. Thickeners which are used are the thickeners described further above.

Pour-on formulations are poured or sprayed onto limited areas of the skin, the active compound penetrating the skin and acting systemically.

Pour-on formulations are prepared by dissolving, suspending or emulsifying the active compound in suitable skin-compatible solvents or solvent mixtures. If desired, further auxiliaries such as colorants, absorption-promoting substances, antioxidants, light protection agents and adhesives are added.

Solvents which may be mentioned are: water, alkanols, glycols, polyethylene glycols, polypropylene glycols, glycerol, aromatic alcohols such as benzyl alcohol, phenyl ethanol, phenoxy ethanol, esters such as ethyl acetate, butyl acetate, benzyl benzoate, ethers such as alkylene glycol alkyl ethers, such as dipropylene glycol monomethyl ether, diethylene glycol mono-butyl ether, ketones such as acetone, methyl ethyl ketone, aromatic and/or aliphatic hydrocarbons, vegetable or synthetic oils, DMF, di- methylacetamide, N-methylpyrrolidone or 2, 2-dimethyl-4-oxy-methylene-1, 3-dioxo- lane.

Colorants are all colorants permitted for use on animals, and they may be dissolved or suspended.

Absorption-promoting substances are for example DMSO, spreading oils such as isopropyl myristate, dipropylene glycol pelargonate, silicone oils, fatty acid esters, triglycerides and fatty alcohols.

Antioxidants are sulphites or metabisulphites, such as potassium metabisulphite, ascorbic acid, butyl hydroxy toluene, butyl hydroxy anisole and tocopherol.

Light protection agents are, for example, Novantisol acid.

Adhesives are, for example, cellulose derivatives, starch derivatives, polyacrylates and natural polymers such as alginates and gelatin.

Emulsions can be administered orally, dermally or as injections.

Emulsions are either of the water-in-oil type or of the oil-in-water type.

They are prepared by dissolving the active compound either in the hydrophobic or in the hydrophilic phase and homogenizing this phase with the solvent of the other phase, with the aid of suitable emulsifiers and, if appropriate, other auxiliaries, such as colorants, absorption-promoting substances, preservatives, antioxidants, light protection agents and viscosity-increasing substances.

The following may be mentioned as the hydrophobic phase (oils): paraffin oils, silicone oils, natural vegetable oils, such as sesame oil, almond oil, castor oil, synthetic triglycerides such as caprylic/capric acid biglyceride, a triglyceride mixture with vegetable fatty acids of chain length C8_12, or other specially selected natural fatty acids, partial glyceride mixtures of saturated or unsaturated fatty acids possibly also containing hydroxyl groups, and mono-and diglycerides of C8/Clo fatty acids.

Fatty acid esters such as ethyl stearate, di-n-butyryl adipate, hexyl laurate, dipropylene glycol pelargonate, esters of a branched fatty acid of medium chain length and saturated fatty alcohols of chain length Cl6-Cz8, isopropyl myristate, isopropyl palmitate, caprylic/capric acid esters of saturated fatty alcohols of chain length Cl2-Cls, isopropyl stearate, oleyl oleate, decyl oleate, ethyl oleate, ethyl lactate, wax-like fatty acid esters such as synthetic duck uropygial gland fat, dibutyl phthalate, diisopropyl adipate and ester mixtures related to the latter, etc.

Fatty alcohols, such as isotridecyl alcohol, 2-octyl dodecanol, cetylstearyl alcohol and oleyl alcohol.

Fatty acids, such as for example oleic acid and mixtures thereof.

The following may be mentioned as the hydrophilic phase: water, alcohols, such as for example propylene glycol, glycerol, sorbitol und mixtures thereof.

The following may be mentioned as emulsifiers: non-ionic surfactants, such as for example, polyoxyethylated castor oil, polyoxyethylated sorbitan monooleate, sorbitan monostearate, glycerol monostearate, polyoxyethyl stearate and alkylphenol polyglycol ether; ampholytic surfactants such as disodium N-lauryl-B-iminodipropionate or lecithin; anionic surfactants such as sodium lauryl sulphate, fatty alcohol ether sulphates and the monoethanolamine salt of mono/dialkylpolyglycol ether orthophosphoric ester.

Further auxiliaries which may be mentioned are: viscosity-increasing and emulsion- stabilizing substances such as carboxymethyl cellulose, methyl cellulose and other cellulose and starch derivatives, polyacrylates, alginates, gelatin, gum arabic, polyvinyl pyrrolidone, polyvinyl alcohol, copolymers of methyl vinyl ether and maleic anhydride, polyethylene glycols, waxes, colloidal silica or mixtures of the substances listed.

Suspensions can be administered orally, dermally or by injection. They are prepared by suspending the active compound in a carrier liquid, with the optional addition of further auxiliaries such as wetting agents, colorants, absorption-promoting substances, preservatives, antioxidants and light protection agents.

Carrier liquids which may be mentioned are all homogeneous solvents and solvent mixtures.

Wetting agents (dispersants) which may be mentioned are the surfactants mentioned further above.

Further auxiliaries which may be mentioned are those mentioned further above.

Semi-solid preparations can be administered orally or dermally. They differ from the above-described suspensions and emulsions only in their higher viscosity.

For the preparation of solid formulations the active compound is mixed with suitable carrier substances, optionally with the addition of auxiliaries, and brought into the desired form.

Carrier substances which may be mentioned are all physiologically compatible solid inert substances. These can be inorganic and organic substances. Inorganic substances are for example common salt, carbonates such as calcium carbonate, hydrogen carbonates, aluminium oxides, silicic acids, argillaceous earths, precipitated or colloidal silicon dioxide and phosphates.

Organic substances are for example sugar, cellulose, foodstuffs and feedstuffs, such as milk powder, animal meals, fine or coarse cereal meals and starches.

Auxiliary substances are preservatives, antioxidants and colorants which have already been listed further above.

Further suitable auxiliaries are lubricants and slip agents such as for example magnesium stearate, stearic acid, talc, bentonites, disintegration-promoting substances, such as starch or crosslinked polyvinyl pyrrolidone, binders such as for example starch, gelatin or linear polyvinyl pyrrolidone and dry binders, such as microcrystalline cellulose.

The active compounds can be also be present in the formulations as a mixture with synergists or with other active compounds which act against pathogenic endoparasites.

Such active compounds are for example L-2,3, 5, 6-tetrahydro-6-phenylimidazothiazole, benzimidazole carbamate, praziquantel, pyrantel and febantel.

Ready-to-use formulations contain the active compound in concentrations of 10 ppm- 20 per cent by weight, and preferably 0.1-10 per cent by weight.

Formulations which are diluted before use contain the active compound in concentrations of 0.5 to 90 % by weight, and preferably 5-50 % by weight.

In general it has proven advantageous to administer amounts of about 1 to about 100 mg of active compound per kg of body weight per day in order to obtain effective results.

Compounds of the formula (1) which have no endoparasitic action or only slight endoparasitic action are suitable for use as valuable intermediates for the preparation of highly effective active compounds.

Preparation examples Example VI-1 N-p-toluenesulphonyl-benzyldimine Benzaldehyde dimethylacetal (8.24 g, 0.12 mol) and p-toluenesulphonamide (17.10 g, 0.10 mol) are heated at 120-130°C and methanol is distilled off continuously. After a reaction time of 4 hours, the mixture is cooled to room temperature and the residue is recrystallized from toluene/methyl t-butyl ether.

Yield = 21.20 g, 82 % of theory.

M. p. = 85-87°C The following compounds of the formula (VI) are prepared in an analogous manner: Ex. No. Rl R2 M. p. / °C VI-2 4-OMe 4-OMe 147-148 VI-3 4-Br 4-OMe 149-150 VI-4 4-F 4-OMe 97-98 VI-5. 4-Me H 138-139 VI-6 H 4-Cl 107-110 Ex. No. RI R2 M. p./°C VI-7 4-Me 4-Cl 134 VI-8 4-OMe 108-109 VI-9 4-Me 4-Me 119-121 VI-10 4-C1 H 194-196 VI-11 4-Cl 4-Me 178-179 VI-12 4-Cl 4-Cl 169-170 VI-13 4-F H 122-124 VI-14 4-Br H 205-206 VI-15 H 4-F 77-78 VI-16 H 4-Br 120-122 VI-17 2, 4-Cl2 H 142 VI-18 4-F 4-Me 117-118

Example IV-1 Cis-l- (p-toluenesulphonyl)-3-acetoxy-4-phenylacetidin-2-one

N-p-toluenesulphonyl-benzaldimine (2.59 g, 10. 00 mmol) and triethylamine (1.31 g, 13.00 mmol) are initially introduced into dichloromethane (20 ml) and cooled to -20°C. A solution of acetoxyacetyl chloride (1.64 g, 12.00 mmol) in dichloromethane (8 ml) is added slowly dropwise and then the mixture is subsequently stirred overnight at room temperature. The reaction solution is washed

successively with 0. 1N hydrochloric acid (20 ml), a saturated aqueous sodium hydrogen carbonate solution (20 ml) and water (20 ml). The organic phase is dried over sodium sulphate, filtered and evaporated in vacuo in a rotary evaporator. The crude product is purified by chromatography on silica gel (eluent : dichloromethane/n-hexane, 1: 1, v/v) followed by recrystallization (dichlormethane/n- hexane).

1.90 g (53 % of theory) of cis-1- (p-toluenesulphonyl)-3-acetoxy-4-phenylacetidin-2- one is obtained.

M. p: 135°C The following compounds of the formula (IV) are prepared analogously:

Ex. No. Rl R2 M. p./°C IV-2 4-OMe 4-OMe 148 1V-3 H H 107-108 IV-4 4-Me H 113-115 IV-5 4-C1 154-155 IV-6 4-Me 4-Cl IV-7 H 4-OMe 94-95 IV-8 4-Me 4-Me 99-101 9 4-Cl H 147-149 IV-10 4-Cl 4-Me 108-111 IV-11 4-Cl 4-Cl 159 IV-12 4-Br H 130-131 IV-13 4-F H 135 IV-14 H 4-F 109-110 IV-15 H 4-Br 114-115 IV-16 4-F 4-Me 166

Example III-1 Methyl N- (toluenesulphonyl)-O-acetyl-3-phenylisoserinyl-2, 2-dimethylglycinate Cis-1-(p-toluenesulphonyl)-3-acetoxy-4-phenylacetidin-2-one (1.80 g, 5.00 mmol), methyl aminoisobutyrate hydrochloride (0.92 g, 6.00 mmol) and N-methyl- morpholine (0.61 g, 6.00 mol) are stirred in dichloromethane (25 ml) overnight at room temperature. The reaction solution is washed with water (20 ml). The organic phase is dried over sodium sulphate, filtered and evaporated in vacuo in a rotary evaporator. The crude product is purified by recrystallization from ethyl acetate.

1.69 g (71 % of theory) of methyl N- (toluenesulphonyl)-O-acetyl-3-phenylisoserinyl- 2, 2-dimethyl-glycinate is obtained.

M. p: 175-176°C The following compounds of the formula (III) are prepared in an analogous manner: Ex. No. R1 R2 R3 R4 R5 M.p./°C III-2 H H Me Me H 177-180 III-3 H H cyclohexyl H 184-186 III-4 H H 2-Me-tetrahydropyranyl H 180-184 III-5 H H 4-OMe-cyclohexyl H 204-207 III-6 H H 4-OEt-cyclohexyl H 199-204 III-7 H 4-Me 4-methylcyclohexyl H 172-173 III-8 H 4-Me cyclohexyl H 196-197 III-9 4-Me H 2-Me-tetrahydropyranyl H 186-189 111-10 4-Me H 4-OMe-cyclohexyl H 161-162 III-11 4-Me H 4-Me-cyclohexyl H 182-183 III-12 4-Me H Me Me H 155-157 III-13 4-Me H cyclohexyl H 191-194 III-14 4-Me H 4-OEt-cyclohexyl H 162-164 111-15 H 4-Cl Me Me H 180-183 III-16 H 4-Cl cyclohexyl H 194-195 III-17 H 4-Cl 2-Me-tetrahydropyranyl H III-18 H 4-Cl 4-OMe-cyclohexyl H 168-169 III-19 H 4-Cl 4-Me-cyclohexyl H1 189-190 III-20 H 4-Cl 4-OEt-cyclohexyl H 183-184 III-21 H 4-Me 2-Me-tetrahydropyranyl H 195-196 III-22 H 4-Me 4-OMe-cyclohexyl H III-23 H 4-Me 4-OEt-cyclohexyl H 178-179 Ex. No. Rl R2 R3 R5 R5 M.p./°C E-24 4-Me 4-Cl Me Me H 167-168 III-25 4-Me 4-C1 cyclohexyl H 177-178 III-26 4-Me 4-Cl 4-Me-cyclohexyl H 212-213 111-27 4-Me 4-Cl 4-OMe-cyclohexyl H 193-194 111-28 4-Me 4-Cl 4-OEt-cyclohexyl H 188-190 111-294-Me 4-C12-Me-tetrahydropyranylH204-205 111-30 4-Me 4-Me 4-Me-cyclohexyl H 181-182 III-31 4-Me 4-Me cyclohexyl H III-32 4-Me 4-Me 2-Me-tetrahydropyranyl H 181-182 III-33 4-Me 4-Me 4-OMe-cyclohexyl H 142-14 III-34 H 4-OMe Me Me H 163-164 III-35 H 4-OMe cyclohexyl H 185-186 III-36 H 4-OMe 4-Me-cyclohexyl H 207-208 III-37 H 4-OMe 4-OMe-cyclohexyl H 199-202 III-38 H 4-OMe 2-Me-tetrahydropyranyl H 194-195 III-39 4-Me 4-Me Me Me H 153-155 III-40 4-Cl H 4-OMe-cyclohexyl H 126-129 III-41 4-C1 H 4-Me-cyclohexyl H 184-185 III-42 4-Cl H Me Me H 112-115 III-43 4-Cl H cyclohexyl H 159-161 III-44 4-Cl 4-Me 4-OMe-cyclohexyl H 168-170 III-45 4-C1 4-Me 4-Me-cyclohexyl H 204-207 III-46 4-Cl 4-Me Me Me H 146-148 111-47 4-Cl 4-Me cyclohexyl H 155-156 III-48 4-Cl 4-Cl 4-OMe-cyclohexyl H 207-210 111-49 4-Cl 4-Cl 4-Me-cyclohexyl H 238-239 111-50 4-Cl 4-Cl Me Me H 184-185 III-51 4-Br H Me Me H 168 III-52 4-Br H cyclohexyl H 182-185 Ex. No. Rl R2 R3 R4 R5 M. p./°C III-53 4-F H 4-Me-cychlohexyl H 189-192 111-54 4-F H Me Me H 162 III-55 4-F H cyclohexyl H 158-159 III-56 H 4-F Me Me H 168 III-57 H 4-Br 4-Me-cyclohexyl H 192-194 III-58 H 4-F cyclohexyl H 178-179 111-59 H 4-Br Me Me H 179-180 111-60 H 4-Br cyclohexyl H 199-200 III-61 4-Br H 4-Me-cyclohexyl H 215-216 111-62 4-F 4-Me 4-Me-cyclohexyl H III-63 4-F 4-Me Me Me H 155-158 III-64 4-F 4-Me cyclohexyl H 91-94

Explanations of the abbreviations: "_ _CH3 cyclohexyl 4-Me-cyclohexyl f SOMe vOEt 4-OMe-cyclohexyl 4-OEt-cyclohexyl 0 CH3 2-Me-tetrahydropyranyl Example II-1 N-(toluenesulphonyl)-3-phenylisoserinyl-2, 2-dimethyl-glycine

Methyl N- (toluenesulphonyl)-O-acetyl-3-phenylisoserinyl-2, 2-dimethylglycinate (1.60 g, 3.36 mmol) is added at room temperature to a solution of sodium hydroxide (0.50 g, 12.6 mmol) in water (30 ml) and subsequently stirred at this temperature for 4 hours. The pH value is adjusted to pH 2-3 with 2N hydrochloric acid and the reaction solution is extracted with ethyl acetate (3 x 50 ml). The organic phase is dried over sodium sulphate, filtered and evaporated in vacuo in a rotary evaporator.

1.30 g (92 % of theory) of N- (toluenesulphonyl)-3-phenylisoserinyl-2, 2-dimethyl- glycine is obtained.

The crude product is reacted further without purification.

The following compounds of the formula (II) are prepared analogously. Ex. No. Rl R2 R3 R4 R5 M. p./°C II-2 H H Me Me H 176-178 II-3 H H 4-OMe-cyclohexyl H 194-196 II-4 H H 2-Me-tetrahydropyranyl H 184-186 II-5 H H cyclohexyl H 206-207 II-6 H H 4-Me-cyclohexyl H 208-210 II-7 H H 4-OEt-cyclohexyl H 146-149 II-8 H 4-Me 4-Me-cyclohexyl H 214-216 II-9 H 4-Me cyclohexyl H 194-195 II-10 4-Me H 2-Me-tetrahydropyranyl H 26-131 II-11 4-Me H 4-OMe-cyclohexyl H 153-156 II-12 4-Me H 4-Me-cyclohexyl H 190-191 II-13 4-Me H Me Me H 197-198 II-14 4-Me H cyclohexyl H 177-179 II-15 4-Me H 4-OEt-cyclohexyl H 156-157 II-16 H 4-Cl Me Me H 195-196 II-17 H 4-Cl 4-OEt-cyclohexyl H 189-190 II-18 H 4-Cl cyclohexyl H 208-209 II-19 H 4-Cl 2-Me-tetrahydropyranyl H 147-149 II-20 H 4-Cl 4-OMe-cyclohexyl H 216-217 II-21 H 4-Cl 4-Me-cyclohexyl H 217-220 II-22 H 4-Me 4-OMe-cyclohexyl H 213-214 II-23 H 4-Me 4-Oet-cyclohexyl H 186-187 11-24 H 4-Me 2-Me-tetrahydropyranyl H 159-161 II-25 4-Me 4-Cl Me Me H 179-180 II-26 4-Me 4-Me 4-OMe-cyclohexyl H 163-164 11-27 4-Me 4-Me 2-Me-tetrahydropyranyl H 148-53 II-28 4-Me 4-Cl cyclohexyl H 150-151 II-29 4-C14-Me-cyclohexylH209-210 II-30 4-Me 4-Cl 4-OMe-cyclohexyl H 178-179 Ex. No. Rl R2 R3 R4 R5 M. p./°C II-31 4-Me 4-C1 4-OEt-cyclohexyl H 180-182 II-32 4-Me 4-C1 2-Me-tetrahydropyranyl H 148-152 II-33 H 4-OMe Me Me H 209-211 II-34 H 4-OMe cyclohexyl H 182-184 H-35 H 4-OMe 4-Me-cyclohexyl H 205-207 II-36 H 4-OMe 4-OMe-cyclohexyl H 211-213 II-37 H 4-OMe 2-Me-tetrahydropyranyl H 127-128 II-38 4-Me 4-Me 4-Me-cyclohexyl H 211-213 II-39 4-Me 4-Me cyclohexyl H 113-115 II-40 4-Me 4-Me Me Me H 204 II-41 4-Cl H 4-Me-cyclohexyl H 207 II-42 4-Cl H Me Me H 212-214 II-43 4-Cl H cyclohexyl H 135 II-44 4-Cl H 4-OMe-cyclohexyl H 102 II-45 4-Cl 4-Me 4-OMe-cyclohexyl H 109 II-46 4-Cl 4-Me 4-mE-cyclohexyl H 218-220 II-47 4-Cl 4-Me cyclohexyl H 151-152 II-48 4-Cl 4-Me Me Me H 187-189 II-49 4-Cl 4-Cl 4-OMe-cyclohexyl H 185-186 II-50 4-Cl 4-Cl 4-Me-cyclohexyl H 230-231 II-51 4-Cl 4-Cl Me Me H 191-192 II-52 4-Br H Me Me H 232 II-53 4-BR H cyclohexyl H 143-144 II-54 4-F H 4-Me-cyclohexyl H 214-215 11-55 H Me H 200-202 II-56 4-F H cyclohexyl H 197 II-57 H 4-F Me Me H 220-221 II-58 H 4-Br Me Me H 124-125 II-59 H 4-F cyclohexyl H 206-27 Ex. No. RI R2 R3 R4 p5 M. p./°C II-60 H 4-Br cyclohexyl H 205-207 II-61 H 4-Br 4-Me-cyclohexyl H 235 II-62 4-Br H 4-Me-cyclohexyl H 195-199 II-63 4-F 4-Me 4-Me-cyclohexyl H 229 II-64 4-F 4-Me Me Me H 196

Example 1 6- (p-Toluenesulphonylaminomethyl)- (a-phenyl)-morpholine-3, 3-dimethyl-2,5- dione

N- (toluenesulphonyl)-3-phenylisoserinyl-2, 2-dimethyl-glycine (1.20 g, 2.86 mmol), methanesulphonic acid (0.20 g, 2.0 mmol) and 1, 2-dichloromethane (200 ml) are heated under reflux in a Soxhlet apparatus (containing a 3A molecular sieve) for about 16 hours (or until the starting material has completely reacted). The dehydrating agent is filtered off and the solvent is evaporated off in vacuo in a rotary evaporator. The crude product is purified by recrystallization from ethyl acetate.

0.63 g (55 % of theory) of 6-(p-toluenesulphonylaminomethyl)-(α-phenyl)- morpholine-3,3-dimethyl-2, 5-dione is obtained.

The following compounds of the formula (I) are prepared analogously: Ex. R1 R2 R3 R4 R5 M. p./°C Nô.. 2 H H Me Me H. 214-216 3 H H 4-OEt-cyclohexyl H 113-116 4 H H 4-Me-cyclohexyl H 241-242 5 H H cyclohexyl H 206-207 6 H 4-Me 4-Me-cyclohexyl H 217-219 7 H H 2-Me-tetrahydropyran-4-yl H 255-257 8 H H 4-OMe-cyclohexyl H 175-177 9 H 4-Me cyclohexyl H 223-225 10 H 4-Cl Me Me H 223-224 11 H 4-C1 cyclohexyl H 224-25 12 H 4-Cl 4-OMe-cyclohexyl H 201-203 13 H 4-Cl 2-Me-tetrahydropyran-4-yl H 115-116 14 H 4-Cl 4-Me-cyclohexyl H 236-237 15 H 4-Cl 4-OEt-cyclohexyl H 185 16 H 4-Me 4-OMe-cyclohexyl H 213-214 17 H 4-Me 4-OEt-cyclohexyl H 177-180 18 H 4-Cl 2-Me-tetrahydropyran-4-yl H 187-190 19 4-Me H 4-OMe-cyclohexyl H 146-147 20 4-Me H 4-Me-cyclohexyl H 224-226 21 4-Me H Me Me H 232-234 22 4-Me H cyclohexyl H 228 23 4-Me H 4-OEt-cyclohexyl H 193-195 24 4-Me 4-Cl cyclohexyl H 215-216 25 4-Me'4-Cl 4-Me-cyclohexyl H 248-249 26 4-Me 4-Cl Me Me H 231-232 27 4-Me 4-Cl 4-OMe-cyclohexyl H 232 28 4-Me 4-Cl 4-OEt-cyclohexyl H 200-203 29 4-Me 4-Cl 2-Me-tetrahydropyran-4-yl H 189-193 30 H 4-OMe Me Me H 214-216 31 H 4-OMe cyclohexyl H 241 32 H 4-OMe 4-Me-cyclohexyl H 189-192 33 H 4-OMe 4-OMe-cyclohexyl H 155-157 34 H 4-OMe 2-Me-tetrahydropyran-4-yl H 194-196 35 4-Me 4-Me 2-Me-tetrahydropyran-4-yl H 215 36 4-Me 4-Me 4-OMe-cyclohexyl H 204-205 37 4-Me 4-Me 4-Me-cyclohexyl H 210-211 38 4-Me 4-Me cyclohexyl H 210-211 39 4-Me 4-Me Me Me H 230-231 40 4-Me H 2-Me-tetrahydropyran-4-yl H 209 41 4-Cl H 4-OMe-cyclohexyl H 228-231 42 4-Cl H cyclohexyl H 228 43 4-Cl H Me H 224-225 44 4-Cl 4-Me 4-OMe-cyclohexyl H 226-229 45 4-Cl 4-Me Me Me H 200-204 46 4-Cl 4-Me 4-Me-cyclohexyl H 245 47 4-Cl 4-Me cyclohexyl H 226-227 48 4-Cl 4-Cl 4-OMe-cyclohexyl H 218-221 49 4-Cl 4-Cl 4-Me-cyclohexyl H 260 50 4-Cl 4-Cl Me Me H 237-239 51 4-Br H Me Me H 220-221 52 H 4-F Me Me H 219-220 53 H 4-Br Me Me H 229-230 54 H 4-Br cyclohexyl H 215-218 55 H 4-F cyclohexyl H 252-254 56 4-Br H 4-Me-cyclohexyl H 252-253 57 4-F H 4-Me-cyclohexyl H 254 58 4-F H cyclohexyl H 240-242 59 4-F H Me Me H 207-209

Biological example: Nematode infection in sheep The compounds were examined for their anthelmintic activity against Haemonchus contorts in sheep. The egg reduction test was used as the test method, in which the number of eggs was determined per gramme of faeces from infected sheep which had or had not been treated (as the control).

Egg reduction test: Sheep (Merino or Blackheaded with a body weight of 25-35 kg) were experimentally infected with 5000 H. contortus third-stage larvae and treated with the test compound at the end of the prepatent period of the parasite. The test compounds were applied orally in gelatin capsules. The anthelmintic activity of the test substances was determined as a function of the reduction in the faecal excretion of eggs in sheep. For the purpose of counting the number of eggs, the faeces of the test animals were used in the fresh state and treated according to the McMaster method modified by Wetzel, and the number of eggs per gramme of faeces was determined. The number of eggs was determined at regular intervals before and after the treatment. The anthelmintic activity is expressed as a function of the reduction in the number of eggs, i. e. the reduction in the number of eggs is expressed in per cent compared with the excretion of eggs prior to treatment : Compound/Ex. no. Activity [%] 7 98.2 17 99.5 53 44.2 55 36.8 27 98.7 30 99.1 31 97.3 35 96.7 57 89.7