WO2005016942A1 - Organophosphoric 4-iminohydantoin derivatives - Google Patents

Abstract

The invention relates to novel organophosporic 4-iminohydantoin derivatives of general formula (I) and above all the use thereof as a pharmaceutical or herbicidal agent.

Description

Title: Organophosphorus 4-iminohydantoin derivatives

description

The invention relates to organophosphorus 4-iminohydantoin derivatives and their use as pharmaceutical or herbicidal compositions.

4-Iminohydantoin derivatives are described in the prior art as antiandrogens, for the treatment of schistosomiasis and as immunomodulators (Perronnet, JM; Girault, P .; Bonne, C. Chem. Abstr. 1977, 87, 85005z; Bernauer, K.; Link, H .; Stohler, H., Chem. Abstr. 1979, 97, 57020q; Short, KM, Ching, BW, Mjalli, AMM, Tetrahedron Lett. 1996, 37, 7489-7492; Link, H .; Stohler, HL Eur J. Med. Chem. 1984, 3, 261-265).

Phosphonic acids are widely used as pesticides, herbicides and pharmaceuticals (Franz, JE, Mao, MK, Sikorski, JA, Glyphosate: a unique global herbicide, ACS Monograph 189, 1997, Neuman, MJ Antimicrob. Chemother 1984, 14, 309-311, Kehler, J. Hansen, HI, Sanchez, C. Bioorg. Med. Chem. Lett. 2000, 10, 2547-2548).

The biosynthesis of isoprenoids via the classic acetate / mevalonate route (Beytia ED, Porter JW. Annu Rev Bioche. 1976; 45: 113-42) and an alternative, mevalonate-independent biosynthetic route, the 2-methyl-D-erythritol route (MEP biosynthetic pathway, synonym DOXP biosynthetic pathway) is known (Rohmer M. Nat Prod Rep. 1999 Oct; 16 (5): 565-74). Both pathways lead to isopentenyl pyrophosphate (IPP), the common precursor of all higher isoprenoids. The DOXP biosynthetic pathway is an advantageous point of action for pharmaceuticals and herbicides (for example WO 99/52515). This is in it justifies that humans and mammals do not have the DOXP biosynthetic pathway. _, _

The present invention relates to compounds of the formula I (hereinafter compounds according to the invention or 4-iminohydantoin derivatives).

where n = 0 -9, preferably 0 -3 methylene.

Ri R2, R3, R4, R5, Rε are the same or different and are selected from the group: hydrogen, hydroxy, halogen, CF ₃ , substituted or unsubstituted alkyl groups, substituted or unsubstituted acyl groups, substituted or unsubstituted alkoxy groups, substituted or unsubstituted cycloalkyl groups , substituted or unsubstituted cycloalkyl (co- ₉₎ alkyl groups, substituted or unsubstituted alkoxy groups cycloalkyl (C0 _9), wherein each alkyl group, each alkoxy group and each acyl group is branched or unbranched and saturated each alkyl group, each alkoxy group and each of acyl group and each cycloalkyl group or one or more double and triple bonds can be unsaturated and one or two carbon atoms of each cycloalkyl group can be replaced by nitrogen, oxygen and sulfur atoms.

R and Rβ are the same or different, as Ri-Re are defined or can be OX ₇ and OXs, with X ₇ or Xs the same or different halogen, substituted or unsubstituted Alkyl groups substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted cycloalkyl (C0-9) alkyl groups, substituted or unsubstituted cycloalkyl (C0 ₉₎ alkoxy groups wherein each alkyl group is branched or unbranched and saturated alkyl group, and each cycloalkyl group or each with one or more double and Triple bonds can be unsaturated and one or two carbon atoms of each cycloalkyl group can be replaced by nitrogen, oxygen, sulfur atom, hydrogen, silyl, cation of an organic or inorganic base, in particular sodium and potassium, ammonium, substituted- ammonium and ammonium compounds, which differ from ethylenediamine or derive amino acids.

It has now been shown that these compounds inhibit or modulate the DOXP biosynthetic pathway, in particular the enzymes and proteins DOXP reductoisomerase, DOXP synthase, GcpE and LytB.

The compounds according to the invention are therefore suitable on the one hand as herbicidal compositions or as pharmaceutical compositions or medicaments for the treatment of diseases in humans and mammals.

In a further embodiment, the 4-I inohydantoin derivatives are selected from the group

as well as from the group

12

13 a-c

The organophosphorus 4-iminohydantoin derivatives of the formula I can form salts in which the hydrogens of the phosphonic acid group are formed by a metal suitable for agriculture, in particular alkali metal salts (Na, K) or alkaline earth metal salts, or ammonium salts or salts with organic amines. Salt formation can likewise take place by addition of a strong acid to the heterocyclic part of the compounds of the formula I. Suitable for this are, for example, HC1, HN0 ₃ , trichloroacetic acid, acetic acid or palmitic acid. Pharmaceutically acceptable salts of the compounds include salts which form the compounds of the formula I according to the invention in their protonated form as the ammonium salt of inorganic or organic acids, such as hydrochloric acid, sulfuric acid, citric acid, maleic acid, fumaric acid, tartaric acid, p-toluenesulfonic acid. The salts, such as sodium salt, potassium salt, calcium salt, ammonium salt, ethanolamine salt, triethylamine salt, are also particularly pharmaceutically suitable. Dicyclohexylamine salt and salts of an amino acid such as arginine salt, aspartic acid salt, glutamic acid salt.

If the organophosphorus 4-iminohydantoin derivatives of the formula I and / or their salts contain one or more asymmetric carbon atoms or else double bonds which are not indicated separately in the general formula, these are also encompassed by formula I. The stereoisomers defined by their special three-dimensional shape, such as enantiomers, diastereomers, Z and E isomers, are all encompassed by the formula I and can be obtained from mixtures of the stereoisomers by customary methods or likewise prepared by stereoselective reactions in combination with the use of stereochemically pure starting materials become.

Special features of Formula I in its definition is explained as follows:

The term "acyl" or "acyl group" is a substituent and means the residue of an organic acid that is formally formed by deletion of an OH group from the organic acid, e.g. the rest of an aliphatic or aromatic carboxylic acid and residues of acids derived therefrom, such as thiocarboxylic acid, possibly N-substituted iminocarboxylic acids or the residues of carbonic acid monoesters, optionally N-substituted carbamic acids, sulfonic acids, sulfinic acids, phosphonic acids, phosphinic acids.

Aliphatic acyl groups are acyl radicals derived from an aliphatic acid, which include the following:

Alkanoyl (e.g. formyl, acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl, pivaloyl etc.); Alkenoyl (e.g. acryloyl, methacryloyl, crotonoyl etc.); alkylthioalkanoyl (e.g. methylthioacetyl, Ethylthioacetyl etc.); Alkanesulfonyl (e.g. mesyl, ethanesulfonyl, propanesulfonyl etc.); Alkoxycarbonyl (e.g. methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl etc.); Alkyl carboxyl (e.g. methyl carbamoyl etc.); (N-alkyl) thiocarbamoyl (e.g. (N-methyl) thiocarbamoyl etc.); Alkyl carbamimidoyl (e.g. methyl carbamimidoyl etc.); oxalo; Alkoxalyl (e.g. methoxalyl, ethoxalyl, propoxalyl etc.).

In the above examples of aliphatic acyl groups, the aliphatic hydrocarbon part, in particular the alkyl group or the alkane radical, may optionally have one or more suitable substituents, such as amino, halogen (for example fluorine, chlorine, bromine etc.), hydroxy, hydroxyimino, carboxy, Alkoxy (e.g. methoxy, ethoxy, propoxy etc.), alkoxycarbonyl, acylamino (e.g. benzyloxycarbonylamino etc.), acyloxy (e.g. acetoxy, benzoyloxy etc.) and the like; as preferred aliphatic acyl radicals with such substituents are e.g. alkanoyl substituted with amino, carboxy, amino and carboxy, halogen, acylamino or the like.

Aromatic acyl radicals are those acyl radicals which originate from an acid having a substituted or unsubstituted aryl group, where the aryl group can include phenyl, toluyl, xylyl, naphthyl and the like; suitable examples are given below: aroyl (for example benzoyl, toluoyl, xyloyl, naphthoyl, phthaloyl etc.); Aralkanoyl (e.g. phenylacetyl etc.); Aralkenoyl (e.g. cinnamoyl etc.); Aryloxyalkanoyl (e.g. phenoxyacetyl etc.); Arylthioalkanoyl (e.g. phenylthioacetyl etc.); Arylaminoalkanoyl (e.g. N-phenylglycyl, etc.); Arenesulfonyl (e.g. benzenesulfonyl, tosyl or toluenesulfonyl, naphthalenesulfonyl etc.); Aryloxycarbonyl (e.g. phenoxycarbonyl, naphthyloxycarbonyl etc.); Aralkoxycarbonyl (e.g. benzyloxycarbonyl etc.); Arylcarbamoyl (e.g. Phenylcarbamoyl, naphthylcarbamoyl etc.); Arylglyoxyloyl (e.g. phenylglyoxyloyl etc.).

In the above examples of aromatic acyl groups, the aromatic hydrocarbon part and / or the aliphatic hydrocarbon part (in particular the alkane radical) may optionally have one or more suitable substituents, such as those which have already been indicated as suitable substituents for the alkyl group or the alkane radical. As an example of preferred aromatic acyl radicals with particular ^{substituents'} be understood with halogen and hydroxy or with halogen and acyloxy and substituted aroyl substituted with hydroxy, hydroxyimino, dihalogenalkanoyloxyimino substituted aralkanoyl, as well as arylthiocarbamoyl (for example phenylthiocarbamoyl etc.); Arylcarbamimidoyl (e.g. phenylcarbamimidoyl etc.).

A heterocyclic acyl radical is understood to mean an acyl radical which comes from an acid with a heterocyclic group; this includes:

Heterocyclic carbonyl, in which the heterocyclic radical is an aromatic or aliphatic 5 to β-membered heterocycle with at least one heteroatom from the group consisting of nitrogen, oxygen and sulfur (e.g. thiophenyl, furoyl, pyrrolocarbonyl, nicotinoyl etc.);

Heterocycle alkanoyl, in which the heterocyclic radical is 5- to 6-membered and has at least one heteroatom from the group consisting of nitrogen, oxygen and sulfur (eg thiophenyl-acetyl, furylacetyl, imidazolylpropionyl, tetrazolylacetyl, 2- (2-amino-4- thiazolyl) -2-methoxyiminoacetyl etc.) and the like.

In the above examples of heterocyclic acyl radicals, the heterocycle and / or the aliphatic Hydrocarbon part may have one or more suitable substituents, such as the same ones that are indicated as being suitable for alkyl and alkane groups.

Unless otherwise defined, “alkyl group” or “alkyl” is a straight-chain or branched-chain alkyl radical having up to 26 carbon atoms, but preferably C1-C6 with methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl , hexyl and Struktursomeren thereof. It ^'may, for example with hydroxy, amino, halogen (eg, fluorine, bromine, chlorine), Oxoresten and alkoxy such as methoxy, ethoxy, be substituted.

Unless otherwise defined, "alkoxy group" or "alkoxy" is a straight-chain or branched-chain alkoxy radical having up to 26 carbon atoms, such as methoxy, ethoxy radicals, etc. It can, for example, contain hydroxyl, amino, halogen, oxo groups and Alkoxy radicals, such as methoxy, ethoxy radicals, may be substituted.

"Cycloalkyl group" is a cyclic radical with preferably 3 to 8 carbon atoms, optionally aromatic and heterocyclic.

"Cycloalkyl (Co-g) alkyl groups" are cyclic compounds with 3 to 8 carbon atoms, unless otherwise defined, which are bonded to the backbone directly or via an alkyl radical. The alkyl radical can be branched, unbranched and saturated or unsaturated with double bonds. Possible substituents of the cycloalkyl radical include alkoxy radicals, alkyl radicals, hydroxy radicals, halogen radicals, amino radicals, oxo radicals. The cycloalkyl groups with the corresponding number of double bonds can also be aromatic (for example phenyl, pyridyl, naphthyl, etc.). In particular, the aromatic cyclic compounds can also contain substituents such as nitro groups and CF ₃ and phenyl radicals. "Cycloalkyl- (C0-9) alkoxy groups" are cyclic compounds with 3 to 8 carbon atoms, which are bonded to the basic structure via an oxygen directly or via an alkoxy radical. The alkoxyl radical can be branched, unbranched and saturated or unsaturated with double bonds. Possible substituents of the cycloalkyl radical include alkoxy radicals (also alkylenedioxy radicals such as methylenedioxy), alkyl radicals, hydroxyl radicals, halogen radicals, amino radicals, oxo radicals. The cycloalkyl groups with the corresponding number of double bonds can also be multiple cycles and aromatic (for example phenoxy, pyridoxy, naphthoxy, etc.). In particular, the aromatic cyclic compounds can also ^■ contain substituents such as nitro groups, CF ₃ groups and phenyl radicals.

Compounds of the formula I with R 1 and R ₂ are preferably hydrogen or one of both methyl. Preference is furthermore given to compounds of the formula I where R and Rβ are hydroxyl, alkoxy, in particular methoxy or ethoxy, halogen. Furthermore, preference is given to compounds of the formula I with n = 0-3 methylene, but preferably 0 or 1. Furthermore, R3, Rε are, independently of one another, hydrogen or methyl.

Compounds with R ₄ or R5, independently of one another, are preferred, alkoxy, acyl, cycloalkyl C (0-9) alkoxy with one or more double bonds or hydrogen.

Also preferred are compounds according to Table 1, namely 3-aralkoxy-4-imino-imidazolidin-2-one and 4-alkoxy (aralkoxy) imino-imidazolidin-2-one.

a.) Herbicidal agent:

The compounds according to the invention as herbicidal compositions can be formulated in various ways, depending on which biological and / or chemical-physical parameters are specified. The following are possible wording: Wettable powders, water-soluble powders, water-soluble concentrates, emulsified concentrates, emulsions, such as oil-in-water and water-in-oil emulsions, sprayable solutions, suspension concentrates, dispersions based on oil or water, oil-miscible solutions, capsule suspensions, dusting agents, granules for the litter - and soil application, granules in the form of micro, spray, elevator and adsorption granules, water-dispersible granules, water-soluble granules, ULV formulations, microcapsules and waxes. These individual formulations are known in principle and are described, for example, in: Winnacker-Küchler, "Chemical Technology", Volume 7, C. Hauser Verlag Munich, 4th Edition 1986, Wade van Valkenburg, "Pesticide Formulations", Marcel Dekker, NY , 1973; K. Martens, "Spray Drying" Handbock, 3rd Ed. 1979, G. Goodwin Ud. London.

The necessary formulation auxiliaries, such as inert materials, surfactants, solvents and other additives, are also known and are described in: Watkins, "Handbock of Insecticide Dust Diluents and Carriers", 2nd Ed., Darland Bocks, Caldwell N.J., H.v. Olphen, "Introduction to Clay Colloid Chemistry"; 2nd Ed., J. Wiley & Sons, N.Y .; C. Marsden, "Solvents Guide"; 2nd Ed., Interscience, N.Y. 1963; McCutcheon's "Detergents and Emulsifiers Annual, MC Publ. Corp., Ridgewood N.J .; Sisley and Wood," Encyclopedia. of Surface Active Agents ", Chem. Publ. Co. Inc., NY 1964; Schönfeldt," interfacial ethylene oxide adducts ", Scientific Publishing Company, Stuttgart 1976; Winnacker-Küchler," Chemical Technology ", Volume 7, C. Hauser Verlag Munich, 4th ed. 1986.

On the basis of these formulations, combinations with other agrochemical active ingredients different from the compounds according to the invention, such as insecticides, acaricides, herbicides, fungicides, safeners, fertilizers such as ammonium sulfate, ammonium hydrogen sulfate, Manufacture urea or mixtures thereof, and / or growth regulators, for example in the form of a finished formulation or as a tank mix.

Spray powders are preparations which are uniformly dispersible in water and which, in addition to a compound according to the invention, in addition to a diluent or inert substance, various ionic and / or nonionic surfactants (wetting agents, dispersing agents), e.g. polyoxyethylated alkylphenols, polyoxethylated fatty alcohols, polyoxethylated fatty amines, fatty alcohol polyglycol ether sulfates, alkane sulfonates, alkylbenzenesulfonates, ligninsulfonic acid 'atrium, 2, 2'-dinaphthylmethane-6, 6' -disulfonic acid sodium, sodium dibutylnaphthalene or also containing sulfonic acid. To prepare the wettable powders, the compounds according to the invention are finely ground as herbicidal compositions, for example in conventional apparatus such as hammer mills, fan mills and air jet mills, and mixed simultaneously or subsequently with the formulation auxiliaries.

Emulsifiable concentrates are prepared by dissolving a compound of the invention in an organic solvent, e.g. 3-methoxypropanal, mono-, di- or oligoesters such as dimethyl malonate,

Dimethyl succinate, dimethyl glutarate or dimethyl adipate, butanol, cyclohexanone, dimethylformamide, xylene or also higher-boiling aromatics, oils (such as soybean oil methyl or rapeseed oil methyl ester) or hydrocarbons or mixtures of the organic solvents.

Examples of emulsifiers that can be used are: alkylarylsulfonic acid calcium salts such as cadodecylbenzenesulfonate or nonionic emulsifiers such as fatty acid polyglycol esters, alkylaryl polyglycol ethers, fatty alcohol polyglycol ethers, propylene oxide-ethylene oxide Condensation products, alkyl polyethers, sorbitan esters such as sorbitan fatty acid esters or block copolymers, for example based on ethylene oxide and propylene oxide.

Water-soluble concentrates are obtained, for example, by dissolving a compound according to the invention in water or in a water-miscible solvent and, if appropriate, adding other auxiliaries such as water-soluble surfactants.

Dusts are obtained by grinding a compound according to the invention with finely divided solid substances, e.g. Talc, natural clays such as kaolin, bentonite and pyrophyllite; or diatomaceous earth.

Suspension concentrates can be water or oil based. You can, for example, by wet grinding using commercially available bead mills and, if necessary, with the addition of surfactants, such as those e.g. already listed above for the other types of formulation.

Emulsions, e.g. Oil-in-water emulsions can be prepared, for example, using stirrers, colloid mills and / or static mixers using aqueous organic solvents and optionally surfactants, such as those e.g. already listed above for the other types of formulation.

Granules can either be produced by spraying a compound according to the invention onto adsorbable, granulated inert material or by applying active substance concentrates by means of adhesives, for example polyvinyl alcohol, sodium polyacrylic acid or else Mineral oils on the surfaces of carriers such as sand, kaolinite or granulated inert material. The compounds according to the invention can also be prepared as fertilizer granules.

Water-dispersible granules are generally produced by the customary methods such as spray drying, fluidized bed granulation, plate granulation, mixing with high-speed mixers and extrusion without solid inert material.

For the production of plate, fluidized bed, extruder and spray granules, see e.g. Procedure in "Spray-Drying Handbook" 3rd ed. 1979, G. Goodwin Ltd., London; J.E. Browning, "Agglomeration", Chemical and Engineering 1967, pages 147 ff; "Perry's Chemical Engineer's Handbook," 5th Ed., McGraw-Hill, New York 1973, pp. 8-57.

For more details on the formulation of

Plant protection products see e.g. G.C. Klingman, "Weed Control as a Science," John Wiley and Sons, Inc., New York, 1961, pp. 81-96, and J.D. Freyer, S.A. Evans, Weed Control Handbook, 5th Ed., Blackwell Scientific Publications, Oxford, 1968, pages 101-103. The herbicidal compositions generally contain 0.01 to 99% by weight, in particular 0.1 to 95% by weight. -%, one or more of a compound of formula I and / or its salts according to the invention.

The active ingredient concentration in wettable powders is, for example, about 10 to 90% by weight, the remainder to 100% by weight consists of customary formulation components. In the case of emulsifiable concentrates, the active substance concentration can be about 1 to 90, preferably 5 to 80,% by weight. Dust-like formulations contain 1 to 30% by weight of active compound, preferably mostly 5 to 20 % By weight of active ingredient, sprayable solutions contain about 0.05 to 80, preferably 2 to 50% by weight of active ingredient. In the case of water-dispersible granules, the active ingredient content depends in part on whether the active compound is in liquid or solid form and which granulating agents, fillers, etc.; be used. The active ingredient content of the water-dispersible granules is, for example, between 1 and 95% by weight, preferably between 10 and 80% by weight.

In addition, the active ingredient formulations mentioned may contain the customary auxiliaries such as adhesives, wetting agents, dispersants, emulsifiers, penetrants, preservatives, antifreeze agents and solvents, fillers, carriers and dyes; Defoamers, adjuvants such as mineral or vegetable oils and their derivatives, evaporation inhibitors and agents that influence pH and viscosity.

The compounds according to the invention as herbicidal compositions can be prepared by customary processes, e.g. by mixing the components with the help of stirrers, shakers or (static) mixers.

In addition to the compounds according to the invention and / or their salts, the formulations mentioned can contain further agrochemical active ingredients, such as safeners, for example in a content of 0.1-50% by weight, preferably 0.5-40% by weight. Finished formulations can be obtained, for example, by producing emulsifiable concentrates or oil dispersions from compounds according to the invention and / or their salts, and other auxiliaries. The content of compounds according to the invention and / or their salts in the finished formulations can vary within wide limits and is generally between: 0.01 and 99% by weight, preferably between 0.1 and 60% by weight. Finally The finished formulations can contain further agrochemical active ingredients such as safeners, for example in a content of 0.01-60% by weight, preferably 0.1-35% by weight.

The application rates of the compounds according to the invention and / or their salts are generally between 0.1 and 200 g ai / ha (ai = active substance), preferably between 0.5 and 100 g ai / ha.

The compounds according to the invention as herbicidal compositions have excellent herbicidal activity against a broad spectrum of economically essential mono- and dicotyledonous harmful plants. Perennial weeds that are difficult to control and that sprout from rhizomes, rhizomes or other permanent organs are also recorded. It is immaterial whether the compounds according to the invention are applied as herbicidal compositions in the pre-sowing, pre-emergence or post-emergence process. Some representatives of the monocotyledonous and dicotyledonous weed flora can be mentioned in detail, which can be controlled by the herbicidal compositions according to the invention without the name being intended to restrict them to certain species.

On the side of the monocot weed species, e.g. Avena, Lolium, Alopecurus, Phalaris, Echinochloa, Digitaria, Setaria as well as Cyperus species from the annual group and on the part of the perennial species Agropyron, Cynodon, Imperata and Sorghum and also perennial Cyperus species.

With dicotyledon weed species, the spectrum of activity extends to species such as Galium, Viola, Veronica, Lamium, Stellaria, Amaranthus, Sinapis, Ipomoea, Matricaria, Abutilon and Sida on the annual side as well as Convolvulus, Cirsiu, Rumex and Artemisia on the perennial weeds.

Harmful plants occurring in rice under the specific crop conditions, e.g. Echinochloa, Sagittaria, Alisma, Eleocharis, Scirpus and Cyperus are also excellently combated by the compounds according to the invention as herbicidal agents.

If the herbicidal compositions according to the invention applied to the soil surface before germination, then either emergence of the ^'weed seedlings is completely prevented or the weeds grow to the cotyledon stage, but then stop growing and finally die completely after three to four weeks have elapsed ,

Cultivated plants, on the other hand, such as crops and ornamental plants, soybeans, cotton, rapeseed, sugar beet, cereals such as wheat, barley, rye, oats or rice, potatoes, tomatoes, peas or corn are only slightly or not at all damaged. This also applies to genetically modified plants, such as transgenic plants, especially those that contain herbicides, pesticides etc. Show resistance. The compounds according to the invention can therefore be used selectively or non-selectively in these crops. Not selectively, for example, to combat unwanted vegetation, such as airports, railway lines, industrial plants, etc.

The invention therefore relates to a process for combating harmful plants, in which at least one compound according to the invention is applied as a herbicidal composition pre-emergence, post-emergence or both to the plants, parts of plants, plant seeds or the area under cultivation. In order to further increase the tolerability and / or selectivity of the compounds according to the invention as herbicidal compositions, it may be advantageous to use them together in a mixture or in succession in succession together with safeners or antidotes.

Compounds which are suitable as safeners or antidots for the herbicidal compositions according to the invention are not, in conclusion, those from EP-A-333 131, EP-A-269 806 (US-A-4,891,057), EP-A-346 620, EP-A- 640 587, EP-A-582 198, WO 91/08202, WO 95/07897 and WO-91/78474 and literature cited therein are known or can be prepared by the processes described there. Other suitable safeners are known from EP-A-94 349 (US-A-4, 902, 304), EP-A-191 736 (US-A-4,881,966) and EP-A-492 366 and the literature cited therein.

In a preferred embodiment, the herbicidal compositions of the present invention therefore contain an additional content of one or more compounds which act as safeners or antidotes.

b.) Medicines:

The compounds according to the invention are suitable for the therapeutic and prophylactic treatment of infections in humans and animals which are caused by viruses, bacteria, unicellular or multicellular parasites or fungi.

The compounds are active against unicellular parasites (protozoa), in particular against pathogens of malaria and sleeping sickness as well as Chagas disease, toxoplasmosis, amoebic dysentery, Leishmaniosis, trichomoniasis, pneumocystosis, balantidiosis, cryptosporidiosis, sarcolocystosis, the Acanthoma, Naeglerose, Coccidiosis, Giardiosis and Lambliosis. They are therefore particularly suitable as malaria prophylaxis and as prophylaxis of sleeping sickness and Chagas disease, toxoplasmosis, amoebic dysentery, Leishmaniosis, trichomoniasis, pneu ozystosis, balantidiosis, cryptosporidiosis, sarcocystosis, acanthambidosis, and Naegleridosis , Giardiosis and Lambliosis.

The compounds according to the invention are therefore suitable and for the treatment of bacterial infections, such as diphtheria, acne vulgaris, listeriosis, erysipelas in animals, gas burns in humans and animals, para-noise burns in humans and animals, tuberculosis in humans and animals, leprosy , and other mycobacteriosis in humans and animals, paratuberculosis in animals, plague, mesenteric lymphadenitis and pseudotuberculosis in humans and animals, cholera, legionnaires' disease, Lyme disease in humans and animals, leptospirosis in humans and animals, syphilis, Campylobacter enteritis in humans and animals , Moraxella keratoconjunctivitis and serositis of animals, brucellosis of animals and humans, anthrax in humans and animals, actinomycosis in humans and animals, streptotrichoses, psittacosis / ornithosis in animals, Q fever, Ehrlichiosis.

The use is also useful in Helicobacter eradication therapy for ulcers of the gastrointestinal tract.

Combinations with another antibiotic can also be used to treat the above-mentioned diseases. Isoniazid, rifampicin, ethambutol, pyrazinamide, streptomycin, protionamide and dapsone are particularly suitable for the treatment of tuberculosis for combination preparations with other anti-infectives.

The active compounds according to the invention are therefore suitable for the treatment of the following viral infections, such as eradication of papillomaviruses for the prevention of tumors, in particular tumors of the genital organs caused by papillomaviruses in humans, eradication of JC viruses and BK viruses, eradication of herpes viruses, eradication of human herpes viruses 8 for the treatment of Kaposi's sarcoma, eradication of cytomegaloviruses before transplants, eradication of Eppstein-Barr viruses before transplantation and for the prevention of Eppstein - Barr virus-associated tumors, eradication of hepatitis viruses for the treatment of chronic liver diseases and for the prevention of liver tumors and liver cirrhosis, eradication of Coxsackieviruses in cardiomyopathies, eradication of Coxsackieviruses in diabetes mellitus patients, eradication of immunodeficiency viruses in human beings animal, treatment of accompanying infections in AIDS patients, treatment of viral inflammation genesis of the respiratory tract (Laryngeal papilloma, hyperplasia, rhinitis, pharyngitis, bronchitis, pneumonias), of the sensory organs (keratoconjunctivitis), of the nervous system (poliomyelitis, meningoencephalitis, encephalitis, subacute sclerosing panencephalitis , SSPE, progressive multifocal leukoencephalopathy, lymphocytic choriomeningitis), the gastrointestinal tract (stomatitis, gingivostomatitis, esophagitis, gastritis, gastroenteritis, diarrheal diseases), the liver and the biliary system (hepatitis, cholangitis, hepatocellular) (lymphocellular cancer) , Lymphadenitis), the hematopoietic system, the genital organs (mumps orchitis), the skin (warts, dermatitis, herpes labialis, cold sores, herpes zoster, shingles), the mucous membranes (papillomas, conjunctival apillomas, hyperplasias, dysplasias), the cardiovascular system (Arteritis, myocarditis, endocarditis, pericarditis), the kidney-urinary system, the genital organs (anogenital lesions, warts, genital warts, pointed condylomas, dysplasias, papillomas, cervical dysplasias, condylomata acuminata, epidermodysplasia, verrucorganal myalgia) , Treatment of foot and mouth disease in cloven hoofed animals, de s Colorado tick fever, dengue syndrome hemorrhagic fever, early summer meningoencephalitis (TBE) and yellow fever.

The pharmaceutically active agents can be prepared in the form of pharmaceutical preparations in dosage units. This means that the preparation in the form of individual parts, e.g. Tablets, coated tablets, capsules, pills, suppositories and ampoules are available, the active ingredient content of which corresponds to a fraction or a multiple of a single dose. The dosage units can e.g. 1, 2, 3 or 4 single doses or 1/2, 1/3 or 1/4 of a single dose. A single dose preferably contains the amount of active ingredient which is administered in one application and which usually corresponds to a whole, a half or a third or a quarter of a daily dose

Non-toxic, inert pharmaceutically suitable carriers are to be understood as solid, semi-solid or liquid diluents, fillers and formulation auxiliaries of all kinds.

Tablets, dragees, capsules, pills, granules, suppositories, solutions, suspensions and emulsions, pastes, ointments, gels, creams, lotions, powders and sprays may be mentioned as preferred pharmaceutical preparations. Tablets, coated tablets, capsules, pills and granules can contain the active ingredient (s) in addition to the usual excipients, such as a) fillers and extenders, e.g. Starches, milk sugar, cane sugar, glucose, mannitol and silica, b) binders, e.g. Carboxymethyl cellulose, alginates, gelatin,

Polyvinylpyrrolidone, c) humectants, e.g. glycerin, d) disintegrants, e.g. agar-agar, calcium carbonate and sodium carbonate, e) solution retarders, e.g. paraffin and f) absorption accelerators, e.g. quaternary ammonium compounds, g) wetting agents, e.g. cetyl alcohol, glycerol monostearate, h) adsorbents, eg kaolin and bentonite and i) Lubricants, for example talc, calcium and magnesium stearate and solid polyethylene glycols or mixtures of the substances listed under a) to i).

The tablets, dragees, capsules, pills and granules can be provided with the customary coatings and casings, optionally containing opacifying agents, and can also be composed such that they release the active ingredient (s) only or preferably in a certain part of the intestinal tract, possibly with a delay, where as Embedding materials, for example Polymer substances and waxes can be used. The active ingredient (s) can optionally also be in microencapsulated form with one or more of the above-mentioned carriers.

In addition to the active ingredient (s), suppositories can contain the usual water-soluble or water-insoluble excipients, e.g. Polyethylene glycols, fats, e.g. Cocoa fat and higher esters (e.g. C14 alcohol with C16 fatty acid) or mixtures of these substances.

In addition to the active ingredient (s), ointments, pastes, creams and gels can contain the usual carriers, e.g. animal and vegetable fats, waxes, paraffins, starch, tragacanth cellulose derivatives, polyethylene glycols, silicones, bentonites, silicic acid, talc and zinc oxide or mixtures of these substances.

In addition to the active ingredient (s), powders and sprays can contain the usual carriers, for example milk sugar, talc, silica, aluminum hydroxide, calcium silicate and polyamide powder or mixtures of these. Sprays can also contain the usual blowing agents, such as chlorofluorocarbons. In addition to the active ingredient (s), solutions and emulsions can contain the customary carriers,

Solubilizers and emulsifiers, e.g. Water, ethyl alcohol, isopropyl alcohol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylene glycol, dimethylformamide, oils, especially cottonseed oil, peanut oil, corn oil, olive oil, castor oil and sesame oil, glycerin, glycerol formaldehyde, tetrahydrofuran fatty acid, tetrahydrofuran fatty acid, tetrahydrofuran fatty acid, tetrahydrofuran fatty acid, tetrahydrofuran fatty acid, tetrahydrofuran fatty acid, tetrahydrofuran fatty acid, tetrahydrofuran fatty acid, tetrahydrofuran or mixtures of these substances.

In addition to the active ingredient (s), suspensions can contain the • usual carriers such as liquid diluents, e.g. Water, ethyl alcohol, propylene glycol, suspending agents e.g. ethoxylated isostearyl alcohols, polyoxyethylene sorbitol and \ sorbitan esters, microcrystalline cellulose,

Contain aluminum metahydroxide, bentonite, agar-agar and tragacanth or mixtures of these substances. ]

The formulation forms mentioned can also contain colorants, preservatives and additives which improve the smell and taste, e.g. Peppermint oil and eucalyptus oil and sweeteners e.g. Saccharin. The compounds of the formula I according to the invention should be present in the pharmaceutical preparations listed above, preferably in a concentration of about 0.1 to 99.5% by weight, preferably of about 0.5 to 95% by weight, of the total mixture.

In addition to the compounds of the formula I, the pharmaceutical preparations can contain further active pharmaceutical ingredients, such as in combination with sulfonamide, sulfadoxine, artemisinin, atovaquone, quinine; Chloroquine, hydroxychloroquine, mefloquine, halofantrine, pyrimethamine, armesin, tetracycline, doxycycline, proguanil, metronidazole, praziquantil, niclosamide, mebendazole, pyrantel, tiabendazole, Diethylcarbazin, Piperazin, Pyrivinum, Metrifonat, Oxamniquin, Bithionol or Suramin. The pharmaceutical preparations are prepared in a customary manner by known methods, for example by mixing the active ingredient (s) with the carrier (s). The preparations mentioned can be used in humans and animals either orally, rectally, parenterally (intravenously, intramuscularly, subcutaneously), intracisternally, intravaginally, intraperitoneally, locally (powder, ointment, drops) and for the treatment of infections in cavities, body cavities. Suitable preparations include injection solutions, solutions and suspensions for oral therapy, gels, infusion formulations, emulsions, ointments or drops. For local therapy, ophthalmic and dermatological formulations, silver and other salts, ear drops, eye ointments, powder or solutions can be used. In animals, the intake can also be in appropriate feed or drinking water. Formulations are made. Furthermore, gels, powders, powders, tablets, prolonged-release tablets, premixes, concentrates, granules, pellets, tablets, boluses, capsules, aerosols, sprays, inhalants can be used in humans and animals. Furthermore, the compounds according to the invention can be incorporated into other carrier materials such as plastics, (plastic chains for local therapy), collagen or bone cement.

In general, it has proven to be advantageous in both human and veterinary medicine to use the active compound or compounds of the formula I in total amounts of about 0.05 to about 600, preferably 0.5 to 200 mg / kg of body weight per 24 hours , if necessary in the form of several single doses, to achieve the desired results. A single dose contains the active ingredient (s) preferably in amounts of about 1 to about 200, in particular 1 to 60 mg / kg body weight. However, it may be necessary to deviate from the dosages mentioned, depending on the dosage on the type and body weight of the patient to be treated, the type and severity of the disease, the type of preparation and administration of the medicament, and the period or interval within which the administration takes place. In some cases it may be sufficient to make do with less than the stated amount of active ingredient, while in other cases the above-mentioned amount of active ingredient must be exceeded. The person skilled in the art can determine the optimum dosage and type of application of the active ingredients required on the basis of his specialist knowledge. The compounds according to the invention can be prepared, for example, by means of stretch synthesis. The basic synthetic route is explained in FIG. 1 (see also Varlet, JM, Fabre, Dunant; H. Tetrahedron Lett. 1981, 37, 1377-1384; Fujii, T., Tanaka, F., Mohri, K., Itaya, T ., Chem. Pharm. Bull. 1974, 22, 2211-2216; Fujii, T., Itaya, T., Wu ^' , CC, K, Tanaka, F., Tetrahedron 1971, 27, 2415-2423).

The following examples and the figures mentioned serve to explain the invention in more detail without restricting the invention thereto.

Examples

General process for the preparation of the compounds 4 a-f according to the invention (see FIG. 1 and Table 1):

10.5 mmol of 1, 1 '-carbonyl-di- (1, 2, 4-triazole) in anhydrous THF (10 mL) was added dropwise with 10 mmol of aminonitrile (la-d), dissolved in anhydrous THF, in 10 minutes the cold. After stirring at room temperature (RT) for 10 minutes, a solution of a suitable hydroxylamine was added and the mixture was stirred at RT for 3 hours. The reaction solution was then concentrated and taken up in EtOAc, washed with sat. Saline and water washed. The organic phase was dried over MgSO4, concentrated and taken up in 15 ml of anhydrous EtOH-HCl. The reaction mixture was stirred at RT for 4 days; the solvent removed in vacuo and the rest taken up in water. The pH was adjusted to 8 with K ₂ C0 ₃ in the cold and extracted with diethyl ether and dried over MgS0. After removal of the solvent, the oily product 4a-f was obtained.

Diethyl 2- (3-benzyloxy-4-imino-5-methyl-2-oxo-imidazolidin-5-yl) ethylphosphonate (4a), colorless oil (65%), IR (film): 1763 (C = 0), 1682 (C = N), 1245, 1218 (P = 0), 1050, 1025 (POC), cm-1;

IH NMR (CDC13) δ (ppm): 1.30 (t, J = 7.12 Hz, 6H), 1.38 (s, 3H), 1.49-2.01 (m, 4H), 4.02-4.13 (m, 4H), 5.12 (s , 2H), 6.65 (s, IH), 7.26-7.40 (m, 5H); 13C NMR (CDC13) δ (ppm): 16.82 (d, 3Jcp = 6.10 Hz), 20.37 (d, Ucp = 142.93 Hz), 26.27, 32.26 (d, 2Jcp = 3.56 Hz), 59.24 (d, 3Jcp = 17.29 Hz ), 62.37 (d, 2Jcp = 6.61 Hz), 79.17, 128.91, 129.63, 130.56, 136.53, 152.04, 160.17; MS (EI) 384.

Diethyl 2- (4-imino-5-methyl-2-oxo-3-phenylethyloxyimidazolidin-5-yl) ethylphosphonate (4b), colorless oil (75%); IR (film): 1760 (C = 0), 1680 (C = N), 1248, 1225 (P = 0), 1050, 1025 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.31 (t, J = 7.12 Hz, 6H), 1.46 (s, 3H), 1.64-2.09 (m, 4H), 3.05 (t, J = 6.78Hz, 2H), 4.03-4.13 (m, 4H), 4.29-4.36 (m, 2H), 6.61 (s, IH), 7.26-7.35

(m, 5H); 13C NMR (CDC13) δ (ppm): 16.81 (d, 3Jcp-6.10 Hz), 20.48 (d, Ucp = 142.93 Hz), 26.03, 32.45 (d, 2Jcp = 3.56 Hz), 34.98, 59.14 (d, 3Jcp = 17.29 Hz), 62.40 (d, 2Jcp = 6.10 Hz), 78.12, 127.31, 129.12, 129.27, 137.50, 153.50; MS (EI) 397.

Diethyl 2- [4-imino-5-methyl-3- (4-methylbenzyloxy) -2-oxo-imidazolidin-5-yl] ethylphosphonate (4c), colorless oil (60%), IR (film): 1758 (C = 0), 1682 (C = N), 1245, 1220 (P = 0), 1057, 1030 (POC), cm-1; IH NMR (CDC13) δ (ppm): 1.30 (t, J = 7.12 Hz, 6H), 1.38 (s, 3H), 1.47-2.00 (m, 4H), 2.35 (s, 3H), 4.01-4.12 (m , 4H), 5.05 (s, 2H), 6.67 (s, IH), 7.19 (d, J = 7.63 Hz,

2H), 7.34 (d, J = 7.89 Hz, 2H); 13C NMR (CDC13) δ (ppm): 16.81 (d, 3Jcp = 5.59 Hz), 20.41 (d, Ucp = 143.43 Hz), 21.26, 26.32, 32.32 (d, 2Jcp = 3.5β Hz), 59.18 (d, 3Jcp = 17.81 Hz), 62.30 (d, 2Jcp = 5.59 Hz), 79.15, 129.92, 130.51, 131.50, 139.98, 153.82, 162.62; MS (EI) 397.

Diethyl 2- (3-benzyloxy-4-imino-2-oxo-imidazolidin-5-yl) ethylphosphonate (4d), colorless oil (62%), IR (film): 1763 (C = 0), 1682 (C = N), 1245, 1220 (P = 0), 1245, 1025 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.32 (t, J = 7.12 Hz, 6H), 1.68-2.19 (m, 4H), 4.01-4.15 (m, 5H), 4.97-5.14 (, 2H), 6.66 ( s, IH), 7.33-7.47 (m, 5H); 13C NMR (CDC13) δ (ppm): 16.82 (d, 3Jcp = 5.59 Hz) ,; 21.43 (d, Ucp = 142.42 Hz), 27.05 (d, 2Jcp = 4.07 Hz), 54.26 (d, 3Jcp = 13.73 Hz), 62.43 (d, 2Jcp = 6.62 Hz), 79.35, 128.09, 129.22, 130.38, 134.48, 152.67, 160.09; MS (EI) 369.

Diethyl 2- (4-imino-2-oxo-3-phenylethyloxy-imidazolidin-5-yl) ethylphosphonate (4e), colorless oil (68%); IR (film): 1758 (C = 0), 1681 (C = N), 1248, 1215 (P = 0), 1030 (POC) cm-1; 1H NMR

(CDC13) δ (ppm): 1.32 (t, J = 7.12 Hz, 6H), 1.73-2.26 (m, 4H), 2.83-3.14 (m, 2H), 3.98-4.19 (m, 5H), 4.27-4.37 (m, 2H), 7.21-7.40 (m, 6H); 13C NMR (CDC13) δ (ppm): 16.82 (d, 3Jcp = 5.60 Hz), 21.61 (d, Ucp = 143.44 Hz), 27.10 (d, 2Jcp = 4.58 Hz), 35.00, 54.31 (d, 3Jcp = 12.72 Hz ), 62.50 (d, 2Jcp = 3.56 Hz), 75.59, 126.72, 127.27, 128.96, 129.41, 148.25, 154.37; MS (EI) 384.

Diethyl 2- [4-imino-3- (4-methylbenzyloxy) -2-oxo-imidazolidin- 5-yl] ethylphosphonate (4f), colorless oil (70%); IR (film): 1760 (OO), 1681 (C = N), 1250, 1225 (P = 0), 1020 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.32 (t, J = 7.12 Hz, 6H), 1.66-2.17 (, 4H), 2.36 (s, 3H), 4.03-4.16 (m, 5H), 4.93-5.10 (m , 2H), 6.71 (s, IH), 7.19 (d, J = 7.88 Hz, 2H), 7.33 (d, J = 7.88 Hz, 2H); 13C NMR (CDC13) δ (ppm): 16.81 (d, 3Jcp = 6.10 Hz), 21.39 (d, Ucp = 142.93 Hz), 21.72, 26.99 (d, 2Jcp = .07 Hz), 54.24 (d, 3Jcp = 13.22 Hz), 62.40 (d, 2Jcp = 4.58 Hz), 79.23, 128.70, 129.52, 131.50, 139.75, 154.54, 160.45; MS (EI) 384.

General process for the preparation of the compounds 5 a-i according to the invention (see FIG. 1 and Table 1):

10.5 mmol of 1, 1'-carbonyldiimidazole or 1, 1 '-carbonyl-di- (1, 2, 4-triazole) in anhydrous THF (10 mL) was added dropwise with 10 mmol of aminonitrile (la-d) within 10 minutes. , dissolved in anhydrous THF, added in the cold. After stirring at room temperature (RT) for 10 minutes, a solution of a suitable hydroxylamine was added and the mixture was stirred at RT for 3 hours.

The reaction solution was then concentrated, triethylamine added and for 45-75 min. heated to 60-70 °. After cooling at RT, the product was taken up in EtOAc and washed with brine, water. The organic phase was dried over MgSO4, concentrated and the remaining oil crystallized with EtOAc / hexane or with

Column chromatography on silica gel with EtOAc or ETOAc / MeOH (9.5: 0.5 v / v) purified. 5a-i was obtained as a colorless solid.

Diethyl 2- (4-benzyloxyimino-5-methyl-2-oxo-imidazolidin-5-yDethylphosphonate (5a), colorless crystals (75%), mp 102 ° C (EtOAc / Hexane); IR (KBr): 1736 (C. = 0), 1678 (C = N), 1247, 1215 (P = 0), 1053, 1028 (POC) cm-1; IH NMR (CDC13) δ (pρm): 1.30 (t, J = 7.12 Hz, 6H ), 1.45 (s, 3H), 1.54-2.04 (, 4H), 3.98-4.13 (, 4H), 5.00 (s, 2H), 6.18 (s, IH), 7.28-7.36 (, 5H), 7.73 (s , IH); 13C NMR (CDC13) δ (ppm): 16.43 (d, 3Jcp = 6.10 Hz), 20.04 (d, Ucp = 142.93 Hz), 26.51, 32.86 (d, 2Jcp = 3.56 Hz), 59.98 (d, 3Jcp = 18.31 Hz), 61.81 (d, 2Jcp = 2.04 Hz), 76.11, 127.94, 128.11, 128.39, 137.54, 152.73, 155.88. Anal. Calcd. for C17H26N305P: C, 53.25; H, 6.83; N, 10.96. Found: C, 53.13; H, 6.89; N, 10.55.

Diethyl 2- (5-methyl-2-oxo-4-phenylethyloxyimino-imidazolidin-5-yl) ethyl phosphonate (5b), colorless crystals (70%), mp 115 ° C (EtOAc / hexane); IR (KBr): 1740 (C = 0), 1678 (C = N), 1248, 1220 (P = 0), 1050, 1025 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.32 (t, J = 7.12 Hz, 6H), 1.48 (s, 3H), 1.69-2.08 (m, 4H), 2.95 (t, J = 6.87 Hz, 2H), 4.04-4. ^' l4 (m, 4H), 4.19 (t, J = 7.12 Hz, 2H), 6.18 (s, IH), 7.19-7.31 (m, 5H), 7.53 (s, IH); 13C MR (CDC13) δ (ppm): 16.45 (d, 3Jcp = 5.59 Hz), 20.26 (d, Ucp = 142.92 Hz), 26.41, 33.03 (d, 2Jcp = 3.56 Hz), 35.53, 59.96 (d, 3Jcp = 18.31 Hz), 61.87 (d, 2Jcp-4.07 Hz), 74.63, 126.32, 128.45, 128.93, 138.52, 152.17, 155.90. Anal. Calcd. for ^" C18H28N305P: C, 54.40; H, 7.10; N, 10.57. Found: C, 54.36; H, 7.10; N, 10.49.

Diethyl 2- [5-methyl-4- (4-methylbenzyloxyimino) -2-oxoimidazolidin-5-yl] ethylphosphonate (5c), colorless crystals

(72%), mp 140 ° C (EtOAc / hexane); IR (KBr): 1736 (C = 0), 1678 (C = N), 1250, 1217 (P = 0), 1055, 1022 (POC) cm-1; 1H NMR (CDC13) δ (ppm): 1.30 (t, J = 7.12 Hz, 6H), 1.46 (s, 3H), 1.53- 2.04 (, 4H), 2.34 (s, 3H), 3.98-4.09 (m, 4H), 4.96 (J = 11.82 Hz, 2H), 6.12 (s, IH), 7.15 (d, J = 7.63 Hz, 2H), 7.23 (d,

J = 8.14 Hz, 2H), 7.62 (s, IH); 13C NMR (CDC13) δ (ppm): 16.44 (d, 3Jcp = 5.59 Hz), 20.06 (d, Ucp = 142.93 Hz), 21.20, 26.54, 32.91 (d, 2Jcp = 3.57 Hz), 59.96 (d, 3Jcp = 17.80 Hz), 61.82 (t, 2Jcp = 5.08 Hz), 76.08, 128.32, 129.09, 134.36, 137.76, 152.50, 155.66. Anal. Calcd. for C18H28N305P: C, 54.40; H, 7.10; N, 10.57. Found: C, 54.49; H, 7.13; N, 10.49. Diethyl 2- (4-benzyloxyimino-2-oxo-imidazolidin-5-yl) ethylphosphonate (5d), colorless crystals (55%), mp 113 ° C (EtOAc / hexane); IR (KBr): 1736 (C = 0), 1676 (C = N), 1245, 1210 (P = 0), 1016 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.31 (t, J = 7.12 Hz, 6H), 1.70-2.10 (m, 4H), 4.02-4.15 (m, 4H), 4.37 (t, J = 5.09 Hz, IH ), 5.00 (s, 2H), 6.47 (s, IH), 7.28-7.35 (,

5H), 7.76 (s, IH); 13C NMR (CDC13) δ (ppm): 16.43 (d, 3Jcp = 5.59 Hz), 20.79 (d, Ucp = 142.42 Hz), 27.61 (d, 2Jcp = 4.07 Hz), 54.25 (d, 3Jcp = 15.77 Hz), 61.89 (d, 2Jcp = 2.55 Hz), 76.13, 127.97, 128.12, 128.40, 137.52, 149.92, 156.97. Anal. Calcd. for C16H24N305P: C, 52.03; H, 6.55; N, 11.38. Found: C, 51.88; H, 6.52; N, 11.19. Diethyl 2- (2-oxo-4-phenylethyloxyimino-imidazolidin-5-yl) ethylphosphonate (5e), colorless crystals (52%), mp 129 ° C (EtOAc / hexane); IR (KBr): 1740 (C = 0), 1676 (C = N), 1245, 1213 (P = 0), 1052, 1033 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.33 (t, J = 7.12 Hz, 6H), 1.78-2.18 (m, 4H), 2.95 (t, J = 6.86 Hz, 2H), 4.02-4.12 (m, 4H) ), 4.19 (t, J = 7.12 Hz, 2H), 4.39 (t, J = 5.09 Hz, IH), 6.39 (s, IH), 7.14-7.28 (m, 5H), 7.50 (s, IH); 13C NMR (CDC13) δ (ppm): 16.46 (d, 3Jcp = 6.11 Hz), 21.16 (d, Ucp = 142.42 Hz), 27.84 (d, 2Jcp = 4.57 Hz), 35.55, 54.31 (d, 3Jcp = 14.24 Hz ), 61.99 (d, 2Jcp = 4.07 Hz), 74.69, 126.34, 128.46, 128.92, 138.49, 149.48, 156.79. Anal. Calcd. for C17H26N305P: C, 53.26; H, 6.82; N, 10.96. Found: C, 53.26; H, 7.00; N, 10.96.

Diethyl 2- [4- (4-methylbenzyloxyimino) -2-oxo-imidazolidin-5-yl] ethylphosphonate (5f), colorless crystals (60%), mp 98 ° C (EtOAc / hexane); IR (KBr): 1732 (C = 0), 1678 (C = N), 1240, 1210 (P = 0), 1048, 1030 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.32 (t, J = 7.12 Hz, 6H), 1.75-2.11 (m, 4H), 2.34 (s, 3H), 4.03-4.13 (m, 4H), 4.37 (t , J = 5.34 Hz, IH), 4.95 (s, 2H), 6.35 (s, IH), 7.15 (d, J = 7.89 Hz, 2H), 7.89 (d, J = 7.89 Hz, 2H), 7.59 (s , IH); 13C NMR (CDC13) δ (ppm): 16.43 (d, 3Jcp = 6.10 Hz), 20.89 (d, Ucp = 142.93 Hz), 21.21, 27.67 (d, 2Jcρ = 4.07 Hz), 54.25 (d, 3Jcp = 14.75 Hz), 61.94 (d, 2Jcp = 4.07 Hz), 76.09, 128.33, 129.11, 134.37, 137.80, 149.73, 156.74. Anal. Calcd. for C17H26N305P: C, 53.26; H, 6.82; N, 10.96. Found: C, 53.21; H, 6.98; N, 10.99, deposition number for the X-ray crystal structure of 5f: CCDC 215669.

Diethyl 2- (4-methoxyimino-2-oxo-imidazolidin-5-yl) ethylphosphonate (5g), colorless crystals (55%), mp 112 ° C (EtOAc / hexane); IR (KBr): 1736 (C = 0), 1678 (C = N), 1240, 1211 (P = 0), 1050, 1016 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.33 (t, J = 7.12 Hz, 6H), 1.77-2.16 (m, 4H), 3.80 (s, 3H), 4.08-4.15 (m, 4H), 4.39 (t, J = 5.08 Hz, IH), 6.34 (s, IH), 7.63 (s, IH); 13C NMR (CDC13) δ (ppm): 16.83 (d, 3Jcp = 6.11 Hz), 21.43 (d, Ucp = 142.93 Hz), 28.17 (d, 2Jcp = 4.07 Hz), 54.67 (d, 3Jcp = 15.77 Hz), 62.39 (d, 2Jcp = 4.58 Hz), 62.44, 149.75, 157.66. MS (FAB); calcd for C10H20N3O5P: 294.1219; found: 294.1228.

Diethyl 2- [4- (4-bromobenzyloxyimino) -2-oxo-imidazolidin-5-yl] ethylphosphonate (5h), colorless crystals (60%), mp 120 ° C (EtOAc / hexane); IR (KBr): 1736 (C = 0), 1680 (C = N), 1240, 1213 (P = 0), 1040, 1016 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.31 (t, J = 7.12 Hz, 6H), 1.70-2.10 (m, 4H), 4.02-4.12 (m, 4H), 4.37 (t, J = 5.34 Hz, IH ), 4.94 (s, 2H), 6.70 (s, IH), 7.21 (d, J = 8.40 Hz, 2H), 7.46 (d, J = 8.40 Hz, 2H), 7.68 (s, IH); 13C

NMR (CDC13) δ (ppm): 16.44 (d, 3Jcp = 6.10 Hz), 20.80 (d, Ucp = 142.93 Hz), 27.60 (d, 2Jcρ = 4.07 Hz), 54.25 (d, 3Jcp = 15.77 Hz), 61.97 (d, 2Jcp-2.54 Hz), 75.27, 129.77, 131.52, 135.14, 136.67, 150.19, 157.13. Anal. Calcd. for Cl6H23BrN305P: C, 42.87; H, 5.17; N, 9.37. Found: C, 42.93; H, 5.17; N, 9.38.

Diethyl (4-benzyloxyimino-2-oxo-imidazolidin-5-yl) methylphosphonate (5i), colorless crystals (60%), mp 110 ° C (EtOAc / hexanes); IR (KBr): 1730 (C = 0), 1686 (C = N), 1240, 1207

(P = 0); 1050, 1030 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.34 (t,

J = 7.12 Hz, 6H), 1.71-2.16 (m, 2H), 4.10-4.18 (, 4H), 4.54

(t, J = 8.39 Hz, IH), 5.00 (s, 2H), 7.26 (s, lH), 7.29-7.38 (m,

5H), 7.66 (s, IH); 13C NMR (CDC13) δ (ppm): 16.43 (t, 3Jcp = 5.60 Hz), 31.63 (d, Ucp = 140.89 Hz), 49.70 (d, 2Jcp = 5.09 Hz), 62.33 (d, 2Jcp = 6.61 Hz), 76.30, 128.09, 128.18, 128.44, 137.26, 149.63 (d, 3Jcp == 19.83 Hz), 155.77. Anal. Calcd. for C15H22N305P: C, 50.70; H, 5.95; N, 11.82. Found: C, 50.34; H, 6.26; N, 11.69.

Diethyl (2-oxo-4-phenylethyloxyimino-imidazolidin-5-yDmethylphosphonate (5j). Colorless crystals (60%), mp 138 ° C (EtOAc / Hexane); IR (KBr): 1736 (C = 0), 1684 ( C = N), 1250, 1210 (P = 0), 1050, 1025 (POC) cm-1; IH MR (CDC13) δ (ρpm): 1.35 (t, J = 7.12 Hz, 6H), 1.97-2.39 ( m, 2H), 2.95 (t, J = 7.12 Hz, 2H), 4.07-4.16 (m, 4H), 4.20 (t, J = 6.87 Hz, 2H), 4.56 (m, IH), ^" 5.91 (s, IH), 7.19-7.32 (m, 5H), 7.53 (s, IH); 13C NMR

(CDC13) δ (ppm): 16.44 (t, 3Jcp = 6.10 Hz), 31.68 (d, Ucp = 140.89 Hz), 35.56, 49.70 (d, 2Jcp = 5.09 Hz), 62.36 (d, 2Jcp = 6.61 Hz), 74.78, 126.35, 128.47, 128.92, 138.43, 149.22 (d, 3Jcp = 19.83 Hz), 155.82. Anal. Calcd. for C16H24N305P: C, 52.03; H, 6.54; N, 11.37. Found: C, 52.17; H, 6.70; N, 11.41.

Diethyl 2- (4-benzyloxyimino-2-oxo-imidazolidin-5-yl) -1, 1-dimethylethylphosphonate (5k). Colorless crystals (52%), mp 133 ° C (EtOAc / hexane); IR (KBr): 1730 (C = 0), 1674 (C = N), 1240,

1209 (P = 0), 1055, 1025 (POC) cm-1; IH MR (CDC13) δ (ppm): 1.23 (q, 6H), 1.33 (t, J = 7.12 Hz, 6H), 1.71-2.08 (m, 2H), 4.08-4.19 (m, 4H), 4.42 (i.e. , J = 10.68 Hz, IH), 5.00 (s, 2H), 7.26 (s, IH), 7.30-7.36 (m, 5H), 7.38 (s, IH); 13C NMR (CDC13) δ (ppm): 16.49 (d, 3Jcp = 5.6 Hz), 21.05, 26.05 (d, Ucp = 4.58 Hz), 33.62 (d, Ucp = 142.42 Hz), 45.45, 51.37 (d, 3Jcp = 2.04 Hz), 62.49 (d, 2Jcp = 7.12 Hz), 76.13, 128.00, 128.17, 128.40, 137.38, 151.46, 155.82. Anal. Calcd. for C18H28N305P: C, 54.40; H, 7.10; N, 10.57. Found: C, 54.45; H, 7.06; N, 10.58.

Diethyl 2- (4-methoxyimino-2-oxo-imidazolidin-5-yl) -1, 1-dimethylethylphosphonate (51). Colorless crystals (50%), Mp

139 ° C (EtOAc / Hexane); IR (KBr): 1740 (C = 0), 1676 (C = N), 1250,

1210 (P = 0), 1057, 1025 (POC) cm-1; IH NMR (CDC13) δ (ppm):

1.24 (q, 6H), 1.33 (t, J = 7.12, 6H), 1.78-2.10 (m, 2H), 3.80 (s, 3H), 4.10-4.17, (m, 4H), 4.44 (d, J = 10.93 Hz, IH), 7.28

(s, IH), 7.69 (s, IH); 13C NMR (CDC13) δ (ppm): 16.46 (d, 3Jcp = 5.60 Hz), 21.05, 26.02 (d, 2Jcp = 4.07 Hz), 33.62 (d, Ucp = 142.42 Hz), 45.48, 51.33 (d, 3Jcp = 2.03 Hz), 61.94, 62.42

(d, 2Jcp = 7.12 Hz), 150.97, 156.24. Anal. Calcd. for C12H24N305P: C, 44.85; H, 7.52; N, July 13 Found: C, 44.97; H, 7.49; N, April 13

General process for the preparation of the compounds 7 a-f according to the invention (see FIG. 2 and Table 1):

3 mmol phenyl isocyanate in anhydrous THF (10 mL) was added to a solution of 3 mmol 4 a-f in anhydrous THF in the cold and stirred for 30 minutes. The solution obtained was concentrated and the remaining oil with

Column chromatography on silica gel eluted with ETOAc / MeOH (9.5: 0.5 v / v). A colorless solid 7 a-f was obtained from crystallization with EtOAc / hexane.

Diethyl 2- (3-benzyloxy-5-methyl-2-oxo-4-phenylcarbamoylimino-imidazolidin-5-yl) ethylphosphonate (7a), colorless crystals

(85%), mp 103 ° C (EtOAc / hexane); IR (KBr): 1713 (C = 0), 1647 (C = N), 1245, 1220 (P = 0), 1050, 1030 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.30 (t, J = 7.12 Hz, 6H), 1.63 (s, 3H), 1.82-

2.25 (m, 4H), 4.02-4.13 (m, 4H), 5.19 (q, J = 8.51 Hz, 2H), 6.85 (s, IH), 7.05-7.49 (m, 10 H), 7.66 (s, IH ); 13C NMR (CDC13) δ (ppm): 16.39 (d, 3Jcp = 5.60 Hz), 19.87 (d, Ucp = 142.96), 25.44, 31.79 (d, 2Jcp = 2.54 Hz), 62.19, 62.22, 78.89, 119.35, 123.44, 128.27 , 128.84, 129.08, 129.08, 130.30, 133.30, 152.90, 160.82, 167.46. Anal. Calcd. for C24H31N406P: C, 57.36; H, 6.21; N, 11.14. Found: C, 57.16; H, 6.38; N, 10.94.

Diethyl 2- (5-methyl-2-oxo-3-phenylethyloxy-4-phenylcarbamoylimino-imidazolidin-5-yl) ethylphosphonate (7b). colorless crystals (85%), mp 123 ° C (EtOAc / hexane); IR (KBr): 1718 (C = 0), 1648 (C = N), 1245, 1220 (P = 0), 1050, 1025 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.29 (t, J = 7.12 Hz, 6H), 1.61 (s, 3H), 1.82-2.24 (m, 4H), 2.75-2.95 (s, br 2H), 4.03- 4.13 (m, 4H), 4.32-4.39 (m, 2H), 6.89 (s, IH), 7.04-7.69 (m, 10H), 7.69 (s, IH); 13C NMR (CDC13) δ (ppm): 16.39 (t, 3Jcp = 5.60 Hz), 19.80 (d, Ucp = 142.42 Hz), 25.42, 31.78 (d, 2Jcp = 3.56 Hz), 34.15, 60.41, 62.24, 77.72, 118.88, 120.08, 123.34, 128.46, 128.60, 128.86, 138.69, 138.70, 152.82, 160.00, 168.10. Anal. Calcd. for C25H33N406P: C, 58.13; H, 6.43; N, 10.84. Found: C, 58.23; H, 6.57; N, 10.80.

Diethyl 2- [4-methyl-3- (4-methylbenzyloxy) -2-oxo-4-phenylcarbamoyliminoimidazoli-din-5-yl] ethylphosphonate (7c), colorless crystals (80%), mp 113 ° C (EtOAc / hexane ); IR (KBr): 1707 (C = 0), 1646 (C = N), 1250, 1230 (P = 0), 1048, 1025 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.30 (t, J = 7.12 Hz, 6H), 1.62 (s, 3H), 1.74-2.04 (m, 4H), 2.28 (s, 3H), 4.01-4.12 (m , 4H), 5.14 (q, J = 8.39 Hz, 2H), 6.83 (s, IH), 6.90-7.40 (m, 9H), 7.66 (s, IH); 13C MR (CDC13) δ (ppm): 16.79 (d, 3Jcp = 5.60 Hz), 19.75 (d, Ucp = 142.42 Hz), 21.69, 25.81 32.17, 62.56, 62.62, 79.21, 119.68, 123.83, 128.80, 129.22, 129.35 , 130.72, 130.70, 138.90, 152.93, 160.71, 167.72. Anal. Calcd. for C25H33N406P: C, 58.13; H, 6.43; N, 10.84. Found: C, 58.04; H, 6.47; N, 10.83. Diethyl 2- (3-benzyloxy-2-oxo-4-phenylcarbamoylimino-imidazolidin-5-yl) ethylphosphonate (7d), colorless crystals

(82%), mp 101 ° C (EtOAc / hexane); IR (KBr): 1710 (C = 0), 1666 (C = N), 1245, 1220 (P = 0), 1050, 1025 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.25 (d, J = 7.13 Hz, 6H), 1.75-2.30 (, 4H), 4.01-4.20 (m, 4H), 4.79 (s, IH), 5.19 (s, 2H), 6.90 (s, IH), 7.10-7.40 (m, 10 H), 7.50 (s, IH); 13C NMR (CDC13) δ (ppm): 16.44 (d, 3Jcp = 5.60 Hz), 21.45 (d, Ucp = 143.44Hz), 25.02 (d, 2Jcp = 4.58Hz), 54.90 (d, 3Jcp = 11.70 Hz), 62.20 (d, 2Jcp = 6.61 Hz), - 78.80, 120.21, 123.45, 128.51, 128.89, 129.13, 129.24, 130.07, 130.25, 153.01, 160.11, 167.73. Anal. Calcd. for C23H29N406P: C, 56.55; H, 5.98; N, 11.46. Found: C, 56.65; H, 6.12; N, 11.40.

Diethyl 2- (2-oxo-3-phenylethyloxy-4-phenylcarbamoylimino-imidazolidin-5-yl) ethyl phosphonate (7e). colorless crystals (83%), mp 118 ° C (EtOAc / hexane); IR (KBr): 1710 (C = 0), 1660 (C = N), 1248, 1228 (P = 0), 1048, 1030 (POC) cm-1; IH NMR (CDC13) δ (ppm): 1.30 (t, J = 7.12 Hz, 6H), 1.80-2.30 (m, 4H), 2.75-2.90 (br, 2H), 4.08-4.20 (, 4H), 4.30- 4.39 (m, 2H), 4.80 (s, IH), 6.90 (s, IH), 7.10-7.60 (, 11H); 13C NMR

(CDC13) δ (ppm): 16.40 (t, 3Jcp = 6.10 Hz), 21.40 (d, Ucp = 143.43 Hz), 25.02 (d, 2Jcp = 4.55 Hz), 34.20, 54.91 (d, 3Jcp = 14.24 Hz), 62.19 (d, 2Jcp = 6.61 Hz), 78.80, 118.22, 120.96, 123.53, 128.77, 129.00, 129.24, 130.07, 138.50, 153.01, 160.21, 167.70. Anal. Calcd. for C24H31N406P: C, 57.36; H, 6.21; N, 11.14. Found: C, 57.27; H, 6.42; N, 10.88.

Diethyl 2- [3- (4-methylbenzyloxy) -2-oxo-4-phenylcarbamoylimino-imidazolidin-5-yl] ethylphosphonate (7f). colorless crystals (85%), mp 113 ° C (EtOAc / hexane); IR (KBr): 1705 (C = 0), 1660 (C = N), 1245, 1218 (P = 0), 1052, 1020 (POC) cm-1; IH NMR (CDC13). δ (ppm): 1.28 (t, J = 6.87 Hz, 6H), 1.77-1.91 (m, 4H), 2.34 (s, 3H), 4.01-4.12 (m, 4H), 4.97 (s, IH), 5.16 (s, 2H), 7.07-7.62 (m, 11H); 13C NMR (CDC13) δ (ppm): 16.32 (d, 3Jcp- 6.10 Hz), 21.33 (d, Ucp = 143.40), 26.17 (d, 2Jcp = 4.58 Hz), 54.46 (d, 3Jcp = 14.24 Hz), 62.17 (d, 2Jcp = 6.61 Hz), 78.79 , 119.00, 120.25, 123.47, 123.79, 129.01, 129.15, 130.31, 138.30, 152.70, 160.73, 167.26. Anal. Calcd. for C24H31N406P: C, 57.36; H, 6.21; N, 11.14. Found: C, 57.35; H, 6.45; N, 10.92.

Diethyl 2- (4-hydroxyimino-5-methyl-2-oxo-imidazolidin-5-yDethylphosphonate (8a), colorless crystals (92%), mp 189 ° C (EtOAc / Hexane); IR (KBr): 1718 (C. = 0), 1691 (C = N), 1245, 1225 (POC), 1050, 1028 (P = 0) cm-1; IH NMR (DMSO-d6) δ (ppm): 1.22 (t, J = 7.12 Hz , 6H), 1.27 (s, 3H), 1.45-1.77 (m, 4H), 3.91-- 4.08 (m, 4H), 7.44 (s, IH), 9.70 (s, IH), 9.77 (s, IH) ; 13C NMR (DMSO-d6) δ (ppm): 16.17 (d, 3Jcp = 5.59 Hz), 19.56 (d, Ucp = 140.90 Hz), 26.03, 32.87 (d, 2Jcp = 3.05 Hz), 58.23 (d, 3Jcp = 19.84 Hz), 60.96 (d, 2 JCP = 6.62 Hz), 152.39, 156.37 Anal Calcd for C10H20N3O5P: C, 40. ^'95; H, 6.87; N, 14:32 Found:.... C, 40.70; H, 7:01 ; N, 14.20.

Diethyl 2- (3-hydroxy-5-methyl-2-oxo-4-phenylcarbamoylimino-imidazolidin-5-yl) ethyl-phosphonate (10a), colorless crystals (90%), mp 189 ° C (EtOAc / hexane); IR (KBr): 1792, 1724 (C = 0), 1655 (C = N), 1250, 1225 (P = 0), 1050, 1020 (POC) cm-1; IH NMR (DMSO-d6) δ (ppm): 1.21 (t, J = 7.12 Hz, 6H), 1.41 (s, 3H), 1.63-1.99 (m, 4H), 3.94-4.02 (m, 4H), 6.96 -7.44 (m, 5H), 7.55 (s, IH), 8.22 (s, 1H), 9.49 (s, IH); 13C NMR (DMSO-d6) δ (ppm): 16.14 (d, 3Jcp = 6.11 Hz), 20.50 (d, Ucp = 143.94 Hz), 24.88, 31.59, 61.03, 61.07, 118.05, 121.67, 128.66, 139.62, 152.44, 159.69, 167.83. Anal. Calcd. for C17H25N406P: C, 49.51; H, 6.11; N, 13.68. Found: C, 49.32; H, 5.93; N, 13.69.

Other derivatives mentioned, such as 8a, 9a-d and k, 10a, 11b, c, can be customary for the person skilled in the art

Derivatization methods can be produced from 5 or 7 (see Figure 2). Diethyl ^' 2- (4-hydroxyimino-5-methyl-2-oxo-imidazolidin-5-yl) ethylphosphonate (8a), colorless crystals (92%), mp 189 ° C (EtOAc / hexane); IR (KBr): 1718 (C = 0), 1691 (C = N), 1245, 1225 (POC), 1050, 1028 (P = 0) cm-1; IH NMR (DMSO-d6) δ (ppm): 1.22 (t, J = 7.12 Hz, 6H), 1.27 (s, 3H), 1.45-1.77 (m, 4H), 3.91- 4.08 (m, 4H), 7.44 (s, IH), 9.70 (s, IH), 9.77 (s, IH); 13C

NMR (DMSO-d6) δ (ppm): 16.17 (d, 3Jcp = 5.59 Hz), 19.56 (d, Ucp = 140.90 Hz), 26.03, 32.87 (d, 2Jcp = 3.05 Hz), 58.23 (d, 3Jcp = 19.84 Hz), 60.96 (d, 2Jcp = 6.62 Hz), 152.39, 156.37. Anal. Calcd. for C10H20N3O5P: C, 40.95; H, 6.87; N, 14.32. Found: C, 40.70; H, 7.01; N, 14.20.

2- (4-benzyloxyimino-5-methyl-2-oxo-imidazolidin-5-yl) ethylphosphonic acid (9a), colorless crystals (82%); Mp 192 ° C; IR (KBr): 2890 (POH), 1740 (C = 0), 1680 (C = N), 1215 (P = 0) cm-1; IH NMR (DMSO-d6) δ (ppm): 1.25 (s, 3H), 1 / 30-1.74 (m, 4H), 4.94 (s, 2H), 7.24-7.39 (m, 5H), 7.61 (s, IH), 10.01 (s, 1H); 13C NMR (DMSO-d6) δ (ppm): 22.42 (d, Ucp = 138.35 Hz), 26.39, 34.09 (d, 2Jcp = 3.05 Hz), 59.10 (d, 3Jcρ = 19.33 Hz), 75.13, 127.72, 127.86, 128.43, 138.58, 154.47, 156.57. Anal. Calcd. for C13H18N305P: C, 47.71; H, 5.54; N, 12.84. Found: C, 47.53; H, 5.69; N, 12.51.

2- (5-methyl-2-oxo-4-phenethyloxyimino-imidazolidin-5-yl) ethylphosphonic acid (9b), colorless crystals (80%); Mp 199 ° C; IR (KBr): 2885 (POH), 1735 (C = 0), 1675 (C = N), 1220 (P = 0) cm-1; IH NMR (DMSO-d6) δ (ppm): 1.29 (s, 3H), 1.40-1.84 (m, 4H), 2.88 (t, J = 6.87 Hz, 2H), 4.04 (t, J = 6.61 Hz, 2H ), 7.19-7.30 (m, 5H), 7.60 (s, IH), 9.94 (s, IH); 13C NMR (DMSO- dδ) δ (ppm): 22.55 (d, Ucp = 137.84 Hz), 26.41, 34.21, 35.25, 59.10 (d, 3Jcp = 19.33 Hz), 74.12, 126.36, 126.58, 129.40, 139.16, 154.01, 156.61. Anal. Calcd. for C14H20N3O5P: C, 49.26; H, 5.90; N, 12.31. Found: C, 48.98; H, 6.11; N, 12.02. 2- [5-Methyl-4- (4-methylbenzyloxyimino) ^" ~ 2-oxo-imidazolidin-5-yl] ethylphosphonic acid (9c), colorless crystals (80%); mp 205 ° C; IR (KBr): 2900 ( POH), 1735 (C = 0), 1670 (C = N), 1225

(P = 0) cm-1; IH NMR (DMSO-d6) δ (ppm): 1.25 (s, 3H), 1.39-1.73 (m, 4H), 2.28 (s, 3H), 4.88 (s, 2H), 7.14 (d, J = 7.88, 2H), 7.26 (d, J = 7.88, 2H), 7.61 (s, IH), 10.04 (s, IH); 13C NMR (DMSO-d6) δ (ppm): 21.13, 22.42 (d, Ucp = 138.35 Hz), 26.40, 34.12, 59.07 (d, 3Jcp = 19.32 Hz), 75.06, 128.01, 129.00, 135.50, 136.87, 154.35, 156.57. Anal. Calcd. for C14H20N3O5P: C, 49.26; H, 5.90; N, 12.31. Found: C, 49.00; H, 6.10; N, 12/12

2- (4-benzyloxyimino-2-oxo-imidazolidin-5-yl) ethylphosphonic acid (9d), colorless crystals (82%); Mp 204 ° C; IR (KBr): 2880 (POH), 1740 (C = 0), 1670 (C = N), 1215 (P = 0) cm-1; IH MR (DMSO-d6) δ (ppm): 1.63-1.85 (m, 4H), 4.22 (t, J = 6.61 Hz, IH), 4.94 (q, J = 12.84 Hz, 2H), 7.32-7.39 (, 5H), 7.68 (s, IH), 10.11 (s, IH); 13C NMR (DMSO-d6) δ (ppm): 23.16 (d, Ucp = 138.35 Hz), 28.98, 53.79 (d, 2Jcp = 18.82 Hz), 75.09, 127.73, 127.88, 128.47, 138.71, 151.62, 157.72. Anal. Calcd. For C12H16N305P: C, 46.01; H, 5.14; N, 13.41. Found: C, 45.80; H, 5.28; N, 13.21.

2- (4-benzyloxyimino-2-oxo-imidazolidin-5-yl) -1, 1-dimethylethylphosphonic acid (9k), colorless crystals (83%); Mp 200 ° C; IR (KBr): 2895 (POH), 1735 (C = 0), 1670 (C = N), 1210

(P = 0) cm-1; IH NMR (DMSO-d6) δ (ppm): 1.09 '(q, 6H), 1.74-1.79 (m, 2H), 4.33 (t, J = 6.11 Hz, IH), 4.94 (q, J = 12.71 Hz, 2H), 7.26-7.89 (m, 5H), 7.71 (s, IH), 10.12 (s, IH); 13C NMR (DMSO-d6) δ (ppm): 22.08, 24.45 (d, Ucp = 2.54 Hz), 33.14 (d, Ucp = 138.86 Hz), 44.14, 50.84 (d, 3Jcp = 7.12 Hz), 75.08, 127.72, 127.85, 128.45, 138.67, 152.80, 157.54. Anal. Calcd. for C14H20N3O5P: C, 49.26; H, 5.90; N, 12.31. Found: C, 48.98; H, 6.15; N, 12/01

Diethyl 2- (3-hydroxy-5-methyl-2-oxo-4-phenylcarbamoylimino-imidazolidin-5-yl) ethyl-phosphonate (10a), colorless crystals

(90%), mp 189 ° C (EtOAc / hexane); IR (KBr): 1792, 1724 {C = 0), 1655 (C = N), 1250, 1225 (P = 0), 1050, 1020 (POC) cm-1; IH NMR

(DMSO-d6 ^' ) δ (ppm): 1.21 (t, J = 7.12 Hz, 6H), 1.41 (s, 3H), 1.63-1.99 (, 4H), 3.94-4.02 (m, 4H), 6.96-7.44 (m, 5H), 7.55 (s, IH), 8.22 (s, 1H), 9.49 (s, IH); 13C NMR (DMSO-d6) δ (ppm): 16.14 (d, 3Jcp = 6.11 Hz), 20.50 (d, Ucp = 143.94 Hz), 24.88, 31.59, 61.03, 61.07, 118.05, 121.67, 128.66, 139.62, 152.44, 159.69, 167.83. Anal. Calcd. for C17H25N406P: C, 49.51; H, 6.11; N, 13.68. Found: C, 49.32; H, 5.93; N, 13.69

2- (5-methyl-2-oxo-3-phenylethyloxy-4-phenylcarbamoyl-iminoimidazolidin-5-yl) ethyl-phosphonic acid (11b), colorless

Crystals (75%); Mp 216 ° C; IR (KBr): 2880 (POH), 1765, 1720

(C = 0), 1650 (C = N), 1215 (P = 0) cm-1; IH MR (DMSO-d6) δ (ppm): 1.30 (s, 3H), 1.46-1.99 (m, 4H), 2.96 (t, J = 7.12 Hz, 2H), 4.24 (t, J = 6.87 Hz, 2H ), 6.88 (s, IH), 7.18-7.46 (m, 10H), 8.60 (s, IH); 13C NMR (DMSO-d6) δ (ppm): 21.36 (d, Ucp = 137.84 Hz), 23.38, 31.62 (d, 2Jcp = 2.54 Hz), 59.04, 59.23, 78.55, 118.06, 120.92, 121.38, 128.92, 129.29, 130.17, 139.61, 152.78, 164.78, 171.76. Anal. Calcd. for C21H25N406P: C, 54.78; H, 5.47; N, 12.16. Found: C, 54.94; H, 5.62; N, 11.89.

2- (5-methyl-3-4-methylbenzyloxy-2-oxo-4-phenylcarbamoylimino-imidazolidin-5-yl) ethylphosphonic acid (11c), colorless crystals (70%); Mp 204 ° C; IR (KBr): 2885 (POH), 1775, 1705 (C = 0), 1650 (C = N), 1230 (P = 0) cm-1; IH NMR (DMSO-d6) δ (ppm): 1.29 (s, 3H), 1.43-1.99 (m, 4H), 2.60 (s, 3H), 5.01 (s, lH), 6.86-7.43 (m, 9H) , 8.80 (s, IH); 13C NMR (DMSO-d6) δ (ppm): 21.23, 22.36 (d, Ucp = 137.84 Hz), 23.36, 31.62 (d, 2Jcp = 2.54 Hz), 59.13 (d, 3Jcp = 19.33 Hz), 78.55, 118.06, 118.35, 121.38, 128.92, 129.29, 130.17, 140.90, 153.78, 171.76. Anal. Calcd. for C21H25N406P: C, 54.78; H, 5.47; N, 12.16. Found: C, 54.54; H, 5.27; N, 11.93.

Process for the preparation of the compound diethyl 2- (4-imino-5-methyl-2-oxo-3-phenylethyloxy-imidazolidin-5-yl) ethylphosphonate hydrochloride (12):

To a solution of 3-amino-3-cyano-3-methyl-propylphosphonic acid diethyl ester (10 mmol) in anhydrous THF (10 mL) was added dropwise with 1.1- 'carbonyl-di- (1 , 2, 4-triazoles) (10.5 mmol), dissolved in anhydrous THF, added in the cold. After stirring at room temperature (RT) for 10 minutes, a solution of 0-phenethylhydroxylamine was added and the mixture was stirred at RT for 3 hours. The reaction solution was then concentrated, and the product was taken up in EtOAc and washed with brine, water. The organic phase was dried over MgS0 ₄ in vacuo, and the remaining oil was taken up in 15 ml of anhydrous EtOH-HCl and stirred for 4 days at room temperature. The solution was concentrated and the residue was taken up in hot EtOAc and 12 was obtained as a colorless solid, filtered and washed with diethyl ether.

Diethyl 2- (4-imino-5-methyl-2-oxo-3-phenylethyloxy-imidazolidin-5-yl) ethylphosphonate hydrochloride (12),), colorless solid (75%), ¹ H NMR (DMSO-d ₅ ) δ (ppm): 1.30 (t, J = 7.10 Hz, 6H), 1.48 (s, 3H), 1.64-2.01 (m, 4H), 3.05 (t, J = 6.78Hz, 2H), 4.03-4.13 (m , 4H), 4.29-4.36 (m, 2H), 6.71 (s,

IH), 7.01-7.35 (m, 5H); ¹³ C NMR (DMSO-d ₆ ) δ (ppm): 16.81 (d, ³ J _cp = 5.40 Hz), 20.48 (d, ^I J _cp = 141.93 Hz), 26.03, 32.45 (d, ² J _cp = 3.40 Hz ), 34.98, 59.14 (d, ³ J _cp = 17.29 Hz), 62.40 (d, ² J _cp = 6.10 Hz), 78.12, 127.31, 129.12, 129.27, 137.50, 153.50, Anal. Calcd. for C ₈ H ₂₉ ClN ₃ 0 ₅ P: C, 49.83; H, 6.73; N, 9.68. Found: C, 49.58; H, 6.72; N, 10/01 General process for the preparation of the compounds 13 ac according to the invention (see FIG. 3):

To a solution of diethyl 2- (4-imino-5-methyl-2-oxo-3-phenylethyloxy-imidazolidin-5-yl) ethylphosphonate (3 mmol) in anhydrous THF (10 mL) was added 3 mmol of p-toluenesulfonyl isocyanate or p -fluorophenyl isothiocyanate or p-toluenesulfonyl chloride added in the cold and stirred for 30 minutes at room temperature. The solution obtained was concentrated and the remaining oil with

Column chromatography on silica gel eluted with ETOAc / MeOH (9.5: 0.5 v / v). A colorless solid 13 a-c was obtained from crystallization with EtOAc / hexane.

Diethyl 2- [5-methyl-2-oxo-3-phenylethylethoxy-4- (4-methylbenzenesulfonyl) carbamoyl imino-imidazolidin-4-yl] ethylphosphonate (13a), colorless solid (85%), mp 122 ° C (mp 122 ° C) EtOAc-hexane); ¹ I NMR (CDC1 ₃ ) δ (ppm): 1.30 (t, J = 7.12 Hz,

6H), 1.47 (s, 3H), 1.66-2.07 (m, 4H), 2.44 (s, 3H), 2.93-3.10 (m, 2H), 4.03-4.14 (m, 4H), 4.29-4.36 (m, 2H), 7.21-7.35 (m,

7H), 7.91 (d, J = 8.14 Hz, 2H); ¹³ C NMR (CDCI3) δ (ppm): 16.80 (d, ³ J _cp = 6.11 Hz), 20.39 (d, ¹ J _cp = 142.93), June 22, December 26,

32.32 (d, ² J _cp = 3.56 Hz), 34.98, 59.27 (d, ² J _cp = 17.50 Hz), 62.48 (d, J = 6.61 Hz), 75.07, 126.71, 127.30, 128.70, 129.12,

129.96, 136.20, 137.49, 138.92, 152.41, 156.68, 162.44. Anal.

Calcd. for C26H35N ₄ O8PS: C, 52.51; H, 5.93; N, 9:42. found:

C, 52.35; H, 6.10; N, 9:32.

Diethyl 2- [methyl-2-oxo-3-phenylethoxy-4- (3-fluorophenyl) thiocarbamoylimino-imidazolidin-5-yl] ethylphosphonate (13b), colorless solid (52%), mp

111.8 ° C (EtOAc-hexane); IH NMR (CDC13) δ (ppm): 1.29 (t, J = 7.12

Hz, 6H), 1.64 (s, 3H), 1.82-2.27 (m, 4H), 3.08 (t, J = 7.38 Hz

2H), 3.98-4.15 (m, 4H), 4.40-4.70 (m, 2H), 6.97-7.81 (, 10

H), 7.78 (IH); 13C NMR (CDC13) δ (ppm): 16.37 (d, 3Jcp = 4.07 Hz), 19.38 (d, Ucp = 142.92 Hz), 25.02, 31.70, 34.67, 58.98 (d, 3Jcp = 17.80 Hz), 62.17 (d, 2Jcp = 7.12 Hz), 78.53, 118.09, 126.57, 126.82, 128.41, 128.92 , 129.23, - 133.63, 138.77, 151.32, 191.46 Anal. Calcd. for C25H23N4F05PS: C, 54.53; H, 5.85; N, 10.17. Found: C, 54.40; H, 6.00; N, 9.95.

Diethyl 2- [5-methyl-2-oxo-3-phenylethyloxy-4- (4-methylbenzenesulfonyl) imino-imidazolidin-5-yl] ethylphosphonate (13c), colorless solid (70%), mp

130 ° C (EtOAc / Hexane); IH NMR (CDC13) δ (ppm): 1.30 (t, J = 7.12 Hz, 6H), 1.77 (s, 3H), 1.82-2.01 (m, 4H), 2.35 (s, 3H), 3.22 (t, J = 7.63 Hz, 2H), 4.04-4.14 (m, 4H), 4.60 (t, J = 7.63 Hz, 2H), 7.17 (d, J = 7.88 Hz, 2H), 7.20-7.28 (m, 5H), 7.77 (d, J = 8.14 Hz, 2H); 13C NMR (CDC13) δ (ppm): 16.40 (t, 3Jcρ = 5.60 Hz), 19.79 (d, Ucp = 142.42), 21.32, 23.80, 31.10, 33.88, 59.40 (d, 2Jcp = 14.75 Hz), 61.40 (d , J = 6.61 Hz), 79.18, 125.93, 126.74, 128.56, 128.80, 129.07, 136.18, 139.9, 148.53, 167.52. Anal. Calcd. for C25H34N307PS: C, 54.43; H, 6.21,; N, 7.61. Found: C, 54.23; H, 6.32; N, 7.50.

Table 1. 3-Aralkoxy-4-imino-imidazolidin-2-one (4, 7) and 4-alkoxy (aralkoxy) imino-imidazolidin-2-one (5).

Connect N ^~ R ^{l ~} RR ^J R ⁴ Ausbe ng ute

4 a 1 HH CH ₃ C ₆ H CH ₂ 65%

4b 1 HH CH ₃ C ₆ H ₅ (CH ₂ ) ₂ 75%

4 c 1 HH CH ₃ 4 -CH ₃ -C ₆ H4-CH ₂ 60%

4 d 1 HHHC ₆ H ₅ CH ₂ 62%

4 e 1 HHHC ₆ Hs (CH ₂ ) ₂ 68%

4 f 1 HHH 4-CH ₃ -C ₆ H ₄ -CH ₂ 70%

5a 1 HH CH ₃ C ₆ H ₅ CH ₂ 75%

5b 1 HH CH ₃ C ₆ H ₅ (CH ₂ ) ₂ 70%

5c 1 HH CH ₃ 4 -CH ₃ -C ₆ H ₄ -CH ₂ 72%

5d 1 HHHC ₆ H ₅ CH ₂ 55% e 1 HHH C6H ₅ (CH ₂ ) 2 52% f 1 HH - H 4-CH3-C ₆ H ₄ -CH2 60% g 1 HHH CH ₃ 55% h 1 HHH 4-Br-C ₆ H4-CH ₂ 60 % i 0 HHH C6H5CH2 60% j 0 HHHC ₆ H ₅ (CH ₂ ) 2 60% k 1 CH ₃ CH ₃ H CδH ₅ CH ₂ 52% 1 1 CH ₃ CH ₃ H CH ₃ 50% a 1 HH CH ₃ C ₆ H ₅ CH ₂ b 85% 1 HH CH ₃ C ₆ H ₅ (CH 2) ₂ 85% c 1 HH CH ₃ 4-CH ₃ -C ₆ H 4 CH ₂ 80% d 1 HHHC ₆ H ₅ CH ₂ ^'82 % e 1 HHHC ₆ H ₅ (CH ₂ ) 2 83% f 1 HHH 4-CH3-C6H4-CH2 85%

Claims

claims 1. Herbicidal composition comprising at least one compound of the formula I and / or salts thereof

where n = 0 -9, preferably 0 -3 methylene, Ri, R ₂ , R ₃ , R, R5, Rε are the same or different and are selected from the group: hydrogen, hydroxy, halogen, CF ₃ , substituted or unsubstituted alkyl groups, substituted or unsubstituted acyl groups, substituted or unsubstituted alkoxy groups, substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted cycloalkyl (C _0-9) alkyl groups, substituted or unsubstituted cycloalkyl (C0-9) alkoxy groups, each alkyl group, each alkoxy group and each acyl group is branched or unbranched and each alkyl group, each alkoxy group and each of acyl group and each cycloalkyl group can be saturated or unsaturated with one or more double and triple bonds and one or two carbon atoms of each cycloalkyl group can be replaced by nitrogen, oxygen and sulfur atoms, R ₇ and R _{B are the} same or different, as Ri-Rε are defined or can be 0X and OXs, with X or Xs the same or different halogen, substituted or unsubstituted alkyl groups, substituted or unsubstituted cycloalkyl groups, substituted or unsubstituted cycloalkyl (C0-9) alkyl groups, substituted or unsubstituted cycloalkyl (Co- 9) alkoxy groups, each alkyl group being branched or unbranched and each alkyl group and each cycloalkyl group saturated or unsaturated with one or more double and triple bonds and one or two carbon atoms of each cycloalkyl group can be replaced by nitrogen, oxygen, sulfur atom, hydrogen, silyl, cation of an organic or inorganic base, in particular sodium and potassium, ammonium, substituted Ammonium and ammonium compounds derived from ethylenediamine or amino acids. 2. Herbicidal composition according to claim 1, additionally comprising one or more further components from the group containing agrochemical active substances of another type, additives and formulation auxiliaries customary in crop protection. 3. A method for controlling harmful plants, wherein the herbicidal composition, defined in accordance with one or more of claims 1 to 2, is applied pre-emergence, post-emergence or both to the plants, parts of plants, plant seeds or the area under cultivation. 4. Medicament containing at least one compound according to claim 1. 5. Pharmaceutical preparation containing at least one medicament according to claim 4. Compounds of formula I according to claim 1 or selected from the group

such as

12

13 a-c and their salts,