Method for preparing herbicide derivatives and intermediate compound

FIELD: organic chemistry, chemical technology, herbicides.

SUBSTANCE: invention describes a method for preparing compounds of the formula (I):

wherein each R1, R2, R3 means independently of one another (C-C6)-alkyl; R can represent also pyridyl; R4 and R5 in common with nitrogen atoms to which they are joined form unsaturated 5-8-membered heterocyclic ring that can be broken by oxygen atom; G means hydrogen atom. Method involves interaction of compound of the formula (II):

wherein R1, R2 and R3 have above given values; R6 is a group RR9N-; R7 is a group R10R11N-; each among R8, R, R10 and R11 means independently of one another hydrogen atom or (C1-C6)-alkyl in inert organic solvent being optionally with the presence of a base with compound of the formula (IV) ,

(IVa)

or (IVb) ,

wherein R4 and R have above given values; H x Hal means hydrogen halide. The prepared compound of the formula (I) wherein G represents ammonium cation is converted to the corresponding compound of the formula (I) by treatment with Brensted's acid wherein G represents hydrogen atom. Also, invention describes compound of the formula (II) wherein R1, R2, R3, R6 and R7 have above indicated values.

EFFECT: improved preparing method.

9 cl, 12 ex

 

The present invention relates to a new method of obtaining herbicide active substituted 3-hydroxy-4-aryl-5-oxadiazoline derivatives.

3-hydroxy-4-aryl-5-oxadiazoline with herbicide activity, and obtaining them are described, for example, in WO 92/16510, EP-A-0508126, WO 95/01971, WO 96/21652, WO 96/25395, WO 97/02243 and WO 99/47525.

With the invention it has been unexpectedly found that substituted 3-hydroxy-4-aryl-5-oxadiazoline derivatives can be obtained in a simple way with high yield and high purity by the condensation of the diamide kilmacanogue acid or monoamide kilmacanogue acid with hydrazine derivatives.

Thus, the present invention relates to a method for producing compounds of formula I

in which R0in each case independently denotes halogen, C1-C6alkyl, C2-C6alkenyl,2-C6quinil, C1-C6haloalkyl, cyano-C1-C6alkyl, C2-C6haloalkyl, cyano-C2-C6alkenyl,2-C6haloalkyl, cyano-C2-C6quinil, the hydroxy-group, hydroxy-C1-C6alkyl, C1-C6alkoxygroup, the nitro-group, an amino group, a C1-C6alkylamino, di(C1-C6alkyl)amino group, a C1-C6alkylcarboxylic, Csub> 1-C6alkylsulfonamides, C1-C6alkylaminocarbonyl,1-C6alkylsulphonyl,1-C6alkylsulphonyl-C1-C6alkyl, C1-C6alkoxycarbonyl-C1-C6alkyl, C1-C6alkylsulphonyl-C2-C6alkenyl,1-C6alkoxycarbonyl-C2-C6alkenyl,1-C6alkylsulphonyl-C2-C6quinil,1-C6alkoxycarbonyl-C2-C6quinil, C1-C6alkoxycarbonyl, cyano, carboxyl, phenyl or aromatic ring which contains 1 or 2 heteroatoms selected from the group comprising nitrogen, oxygen and sulfur, while the last two aromatic rings can be substituted C1-C3the alkyl, C1-C3haloalkyl, C1-C3alkoxygroup, C1-C3haloalkoxy, halogen, cyano or nitro-group, or Rotogether with the adjacent substituents R1, R2and R3, forms a saturated or unsaturated With3-C6hydrocarbon bridge which may be interrupted by 1 or 2 heteroatoms selected from the group comprising nitrogen, oxygen and sulfur, and/or may be substituted With1-C4the alkyl, R1, R2and R3each independently mean hydrogen, halogen, C1-C6Alki is, With2-C6alkenyl,2-C6quinil,3-C6cycloalkyl, C1-C6haloalkyl,2-C6haloalkyl,1-C6alkoxycarbonyl-C2-C6alkenyl, C1-C6alkylsulphonyl-C2-C6alkenyl, cyano-C2-C6alkenyl, nitro-C2-C6alkenyl,2-C6haloalkyl, C1-C6alkoxycarbonyl-C2-C6quinil,1-C6alkylsulphonyl-C2-C6quinil, cyano-C2-C6quinil, nitro-C2-C6quinil,3-C6halachically, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkylthio-C1-C6alkyl, cyano, C1-C4alkylsulphonyl, C1-C6alkoxycarbonyl, the hydroxy-group, C1-C10alkoxygroup,3-C6alkenylacyl,3-C6alkyloxy, C1-C6haloalkoxy,3-C6haloalkylthio,1-C6alkoxy-C1With6alkoxygroup, mercaptopropyl, C1-C6allylthiourea, C1-C6haloalkylthio, C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, nitro-group, an amino group, a C1-C6alkylamino, di(C1-C6alkyl)AMI is Gruppo or fenoxaprop, where the phenyl ring may be substituted C1-C3the alkyl, C1-C3haloalkyl, C1-C3alkoxygroup, C1-C3haloalkoxy, halogen, cyano or nitro-group,

R2may also represent a phenyl, naphthyl or 5 - or 6-membered aromatic ring which may contain 1 or 2 heteroatoms selected from the group comprising nitrogen, oxygen and sulfur, with the phenyl ring, naftalina ring system and 5 - or 6-membered ring may be substituted with halogen, C3-C8cycloalkyl, hydroxy-group, mercaptopropyl, amino group, cyano, a nitro-group or formyl, and/or phenyl ring, naftalina ring system and 5 - or 6-membered aromatic ring can be substituted C1-C6the alkyl, C1-C6alkoxygroup, hydroxy-C1-C6the alkyl, C1-C6alkoxy-C1-C6the alkyl, C1-C6alkoxy-C1-C6alkoxygroup, C1-C6alkylcarboxylic, C1-C6alkylthiol, C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, mono-C1With6alkylaminocarbonyl, di(C1-C6alkyl)amino group, a C1-C6alkylcarboxylic,1-C6alkylsulphonyl(C1-C6alkyl)aminogroup is, With2-C6alkenyl,3-C6alkenylacyl, hydroxy-C3-C6alkenyl,1-C6alkoxy-C3-C6alkenyl,1-C6alkoxy-C3-C6alkenylacyl,2-C6alkenylboronic,2-C6alkenylsilanes,2-C6alkanesulfonyl, C2-C6alkanesulfonyl, mono - or di-(C2-C6alkenyl)amino group, With1-C6alkyl(C3-C6alkenyl)amino group, With2-C6alkenylamine,2-C6alkenylboronic(C1-C6alkyl)amino group, With2-C6the quinil,3-C6alkyloxy, hydroxy-C3-C6the quinil, C1-C6alkoxy-C3-C6the quinil,1-C6alkoxy-C4-C6alkynylamino,2-C6alkylammonium,2-C6alkylalcohol,2-C6alkylsulfonyl,2-C6alkylsulfonyl, mono - or di-(C3-C6quinil)amino group, With1-C6alkyl(C3-C6quinil)amino group, With2-C6alkylcarboxylic or2-C6alkenylboronic(C1-C6alkyl)amino group and/or phenyl ring, naftalina ring system and 5 - or 6-membered ring is an aromatic ring may be substituted with halogen substituted C 1-C6the alkyl, C1-C6alkoxygroup, hydroxy-C1-C6the alkyl, C1-C6alkoxy-C1-C6the alkyl, C1-C6alkoxy-C1-C6alkoxygroup, C1-C6alkylcarboxylic, C1-C6alkylthiol, C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, mono-C1-C6alkylaminocarbonyl, di(C1-C6alkyl)amino group, With1-C6alkylcarboxylic,1-C6alkylsulphonyl(C1-C6alkyl)amino group, With2-C6alkenyl,1-C6alkenylacyl, hydroxy-C3-C6alkenyl,1-C6alkoxy-C2-C6alkenyl, C1-C6alkoxy-C3-C6alkenylacyl,2-C6alkenylboronic, C2-C6alkenylsilanes,2-C6alkanesulfonyl, C2-C6alkanesulfonyl, mono - or di-(C2-C6alkenyl)amino group, a C1-C6alkyl-(C3-C6alkenyl)amino group, With2-C6alkenylamine,2-C6alkenylboronic(C1-C6alkyl)amino group, With2-C6the quinil,3-C6alkyloxy, hydroxy-C3-C6the quinil, C1-C6alkoxy-C3-C the quinil,1-C6alkoxy-C4-C6alkynylamino,2-C6alkylammonium,2-C6alkylalcohol,2-C6alkylsulfonyl,2-C6alkylsulfonyl, mono - or di-(C3-C6quinil)amino group, With1-C6alkyl(C3-C6quinil)amino group, With2-C6alkylcarboxylic or2-C6alkenylboronic(C1-C6alkyl)amino group and/or phenyl ring, naftalina ring system and 5 - or 6-membered aromatic ring may be substituted by a radical of the formula COOR50, CONR51, SO2NR53R54or SO2OR55where R50, R51, R52, R53, R54and R55each independently from each other represents C1-C6alkyl, C2-C6alkenyl or1-C6quinil or substituted with halogen, hydroxy-group, alkoxygroup, mercaptopropyl, amino group, cyano, a nitro-group, alkylthiol, alkylsulfonyl or alkylsulfonyl C1-C6alkyl, C2-C6alkenyl or3-C6quinil, n means 0, 1 or 2,

R4and R5each independently of one another denotes hydrogen, C1-C12alkyl, C1-C12haloalkyl,2-C8alkenyl, -C8quinil,1-C10alkoxy-C1-C8alkyl, poly-C1-C10alkoxy-C1With8alkyl, C1-C10alkylthio-C1-C8alkyl, C3-C8cycloalkyl,3-C8halachically, 4-8-membered heterocyclyl, phenyl, αor β-naphthyl, phenyl-C1With6alkyl, αor β-naphthyl-C1-C6alkyl, 5 - or 6-membered heteroaryl or 5 - or 6-membered heteroaryl-C1-C6alkyl, such aromatic and heteroaromatic rings may be substituted with halogen, C1-C6the alkyl, C1-C6haloalkyl, C1-C6alkoxygroup, C1-C6haloalkoxy, a nitro-group, or by cyano, or R4and R5together with the nitrogen atoms to which they are attached, form a saturated or unsaturated 5-8-membered heterocyclic ring, which 1) can be interrupted by oxygen, sulfur or the group-NR14-and/or may be substituted by halogen, C1-C10the alkyl, C1-C10haloalkyl, hydroxy-group, C1-C6alkoxygroup,1-C6alkoxy-C1-C6alkoxygroup, C1-C6haloalkoxy, mercaptopropyl, C1-C6alkylthiol,3-C7cycloalkyl, heteroaryl, heteroaryl-C1-With6alkyl is m, by phenyl, phenyl-C1-C6the alkyl or benzyloxy, where the phenyl rings of the last three substituents in turn may be substituted by halogen, C1-C6the alkyl, C1-C6haloalkyl, C1-C6alkoxygroup, C1-C6haloalkoxy or nitrogroup, and/or 2) may contain a condensed or spirostanol alkylenes or alkenylamine chain with 2 to 6 carbon atoms, which is optionally interrupted by oxygen or sulfur, or at least one ring atom saturated or unsaturated heterocyclic ring forms a bridge connection with this alkalinous or alkenylamine circuit, with R14means hydrogen, C1-C4alkyl, C1-C6alkylsulphonyl, C1-C6alkylsulfonyl, C3-C6alkenyl or3-C6quinil, and G denotes the hydrogen equivalent of a metal ion or an ammonium cation, sulfone or phosphonium, which consists in the fact that the compound of formula II

in which R0, R1, R2, R3and n have the above meaning, R6is an R8R9N-, R7is an R10R11N or R12O-and R8, R9, R10,R11and R12each independently of one another denotes hydrogen, C1-C alkyl, C1-C6haloalkyl,3-C6alkenyl or benzyl, where the phenyl ring of the benzyl group may be substituted With1-C4by alkyl, halogen, C1-C4haloalkyl, C1-C4alkoxygroup or nitrogroup, is subjected to the interaction in an inert organic solvent, optionally in the presence of a base, with a compound of formula IV, IVa or IVb

where R4and R5have the above values, and N·l represents a hydrogen halide, and the resulting compound of the formula I in which G represents an equivalent of a metal ion or an ammonium cation, optionally transferred by salt formation in the corresponding salt of the compounds of formula I in which G represents a cation of sulfone or phosphonium, or by treatment with acid Bronsted converted into the corresponding compound of formula I in which G represents hydrogen.

The present invention relates also to a direct ("in situ") transform in the same reaction vessel compounds of formula I, the compounds of formula Ia

in which R0, R1, R2, R3,R4,R5and n have the meanings indicated for the formula I, a

G0means the group-C(O)-R30, -C(X1)-X2-R31With(X 3)-N(R32)-R33, -SO2-R34or-P(X4)(R35)-R36where X1, X2, X3and X4each independently of one another denotes oxygen or sulphur,

R30means unsubstituted or substituted with halogen With1-C20alkyl, C1-C20alkenyl,1-C8alkoxy-C1-C8alkyl, C1-C8alkylthio-C1-C8alkyl, poly-C1-C8alkoxy-C1-C8alkyl or unsubstituted or substituted by halogen, C1-C6the alkyl or C1-C6alkoxygroup3-C8cycloalkyl, in which at least one member ring optionally replaced by oxygen and/or sulfur, With3-C6cycloalkyl-C1-C6alkyl, heterocyclyl-C1-C6alkyl, heteroaryl-C1-C6alkyl, unsubstituted or substituted with halogen, a cyano, a nitro-group, With1-C6the alkyl, C1-C6alkoxygroup,1-C6haloalkyl,1-C6haloalkoxy,1-C6alkylthiophene or1-C6alkylsulfonyl phenyl, unsubstituted or substituted with halogen, a nitro-group, cyano, C1-C6the alkyl, C1-C6alkoxygroup,1-C6haloalkyl or1-C6haloalkoxy phenyl-C1-the 6alkyl, unsubstituted or substituted with halogen or1-C6the alkyl heteroaryl, unsubstituted or substituted with halogen or1-C6the alkyl, phenoxy-C1-C6alkyl or unsubstituted or substituted by halogen, amino or1-C6the alkyl, heteroaromatic - C1-C6alkyl,

R31means unsubstituted or substituted with halogen With1-C20alkyl, C2-C20alkenyl,1-C8alkoxy-C2-C8alkyl, poly-C1-C8alkoxy-C2-C8alkyl, unsubstituted or substituted with halogen, C1-C6the alkyl or C1-C6alkoxygroup3-C8cycloalkyl,3-C6cycloalkyl-C1-C6alkyl, heterocyclyl-C1-C6alkyl, heteroaryl-C1-C6alkyl, unsubstituted or substituted with halogen, a cyano, a nitro-group, With1-C6the alkyl, C1-C6alkoxygroup,1-C6haloalkyl or1-C6haloalkoxy phenyl or benzyl,

R32and R33each independently of one another denotes hydrogen, unsubstituted or substituted with halogen, C1-C8alkyl, C3-C8cycloalkyl,1-C8alkoxygroup,3-C8alkenyl,1-C8alkoxy-C1-C8alkyl,unsubstituted or substituted with halogen, With1-C8haloalkyl,1-C8the alkyl or C1-C8alkoxygroup phenyl or benzyl, or

R32and R33together form3-C6alkylenes a circuit in which a carbon atom optionally replaced by oxygen or sulphur,

R34means unsubstituted or substituted with halogen With1-C8alkyl, C3-C8alkenyl,3-C8haloalkyl,3-C8quinil,3-C8haloalkyl or unsubstituted or substituted by halogen, C1-C6the alkyl, C1-C6alkoxygroup,1-C4haloalkyl,1-C4haloalkoxy, cyano or nitro-group is phenyl or benzyl,

R35and R36each independently of one another denotes unsubstituted or substituted with halogen With1-C8alkyl, C1-C8alkoxygroup, C1-C8alkylamino, di(C1-C8alkyl)amino group, With1-C8allylthiourea,2-C8altertekhnogrupp,3-C7cycloalkylation or unsubstituted or substituted with halogen, a nitro-group, cyano, C1-C4alkoxygroup,1-C4haloalkoxy,1-C4alkylthiol, C1-C4haloalkylthio,1-C4the alkyl or C1-C4halo is Kilom phenyl, fenoxaprop or phenylthiourea, namely, that the compounds of formula I, optionally in the presence of an acid binding agent or catalyst, is subjected to the interaction with an electrophile of formula XII or XIId

where G0, R32and X3have the above values, except that R32does not mean hydrogen, a L is a leaving group, for example R30C(O)O-, R31X2or halogen, preferably chlorine, bromine or iodine.

Depending on the substituents R0-R5, G and G0compounds of formulas I and Ia can exist in the form of geometric and/or optical isomers or mixtures of isomers (atropisomers), and if G denotes the hydrogen equivalent of a metal ion or an ammonium cation, sulfone or phosphonium, they can exist in the form of the tautomers or mixtures of tautomers.

If the original materials are used not in the form of pure enantiomers, the above-described reactions of compounds of formulas I and Ia generally receive in the form of racemates or mixtures of diastereoisomers, which if necessary can be divided on the basis of differences in their physico-chemical properties according to known methods, such as fractional crystallization followed by the formation of salts with optically pure bases, acids or what omplexity metals or chromatography, for example, liquid chromatography high resolution (IHVR) on the cellulose acetate.

According to the present invention, under the compounds of formulas I and Ia are understood and enriched and optically pure forms of the corresponding stereoisomers and racemates and diastereomers. If the description is not given specific guidance in relation to individual optical antipodes, the compounds of the above formula refers to the racemic mixture obtained proposed in the invention method. In the presence of aliphatic double bonds C=C may show geometric isomerism.

The present invention relates also to the salts which the compounds of formulas I and Ia capable of combining with acids. Suitable for the formation of acid additive salts of the acids are both organic and inorganic acids. As examples of such acids can be called hydrochloric acid, Hydrobromic acid, nitric acid, phosphoric acid, sulfuric acid, acetic acid, propionic acid, butyric acid, valeric acid, oxalic acid, malonic acid, fumaric acid, organic sulfonic acids, lactic acid, tartaric acid, citric acid and salicylic acid.

Given their acidity of the compounds of formula I, in which G denotes hydrogen, can be a simple way is to transfer in the presence of bases (proton acceptor) into the corresponding salt (where G represents for example, the equivalent of a metal ion or an ammonium cation), as described, for example, in EP-A 0508126. As a basis you can use the normal acceptor of protons. As an example, such salts can be called alkali metal salts, for example sodium and potassium salts, alkaline-earth metals, for example calcium and magnesium salts, ammonium salts, i.e. salts of unsubstituted ammonium, and salts of mono - or polishmaster ammonium compounds, for example salts of triethylamine, methylamine, or salts with organic bases or other cations, for example cations of sulfone or phosphonium. The cations of sulfone include, for example, the three cations(C1-C4alkyl)sulfone, which can be obtained from the corresponding salts of alkali metals, for example, by converting one salt to another, for example using effects for cation-exchanger.

Among the hydroxides of the alkali and alkaline-earth metals as salt-forming agents should be particularly noted, for example, hydroxides of lithium, sodium, potassium, magnesium and calcium, especially the hydroxides of sodium and potassium. Acceptable soleobrazutaya agents are described, for example, in WO 97/41112.

Examples of amines suitable for the formation of ammonium salts are ammonia and primary, secondary, and tertiary1-C18the bonds alkylamines,1-C4hydroxyalkyl the us and 2-C4alkoxyalkyl, for example methylamine, ethylamine, n-Propylamine, Isopropylamine, the four isomeric state of butylamine, n-amylamine, isoamylamine, hexylamine, heptylamine, octylamine, nonylamine, decylamine, pentadecylic, hexadecylamine, heptadecyl, octadecylamine, methylethylamine, metrizability, methylhexanamine, methylenediamine, methylpentadiene, methyloctadecane, ethylbutylamine, ethylheptylamino, atractylis, ekilganiligini, getselection, dimethylamine, diethylamine, di-n-Propylamine, Diisopropylamine, di-n-butylamine, di-n-amylamine, vitaminen, digoxigenin, gigatronik, dioctylamine, ethanolamine, n-propanolamine isopropanolamine, N,N-diethanolamine, N-ethylpropylamine, N-butylethylamine, allylamine, n-butenyl-2-amine, n-pentenyl-2-amine, 2,3-dimethylbutene-2-amine, dibutyl-2-amine, n-hexenyl-2-amine, Propylenediamine, trimethylamine, triethylamine, tri-n-Propylamine, triisopropanolamine, tri-n-butylamine, triisobutylene, tri-sec-butylamine, tri-n-amylamine, methoxyethylamine and amoxicillin, heterocyclic amines, for example pyridine, quinoline, isoquinoline, morpholine, N-methylmorpholine, thiomorpholine, piperidine, pyrrolidine, indoline, Hinkley and asain, primary arylamines, for example anilines, methoxyaniline, ethoxyaniline, o-, m - and p-toluidine, finlandiae, benzidine, naphthylamines and o-, m - and p-chloraniline first ever shall triethylamine, Isopropylamine and Diisopropylamine.

In the above values radicals under the halogen is meant fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.

Alkyl groups, the above values of the substituents are, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl or tert-butyl, and the isomers pentile, hexyl, heptyl, Attila, Manila, decyl, undecyl and dodecyl.

Haloalkyl groups preferably have a chain length of from 1 to 6 carbon atoms. Haloalkyl represents, for example, vermeil, deformity, diperchlorate, trifluoromethyl, chloromethyl, dichloromethyl, dichlorofluoromethyl, trichloromethyl, 2,2,2-triptorelin, 2-foretel, 2-chloroethyl, 2,2-dottorati, 2,2-dichloroethyl, 2,2,2-trichloroethyl or pentafluoroethyl, preferably trasmital, deformity, diperchlorate, trifluoromethyl or dichloromethyl.

Alkoxygroup preferably have a chain length of from 1 to 6 carbon atoms. Alkoxygroup represents, for example, a methoxy group, ethoxypropan, n-propoxylate,isopropoxy, n-butoxypropyl, out-butoxypropyl, sec-butoxypropyl, tert-butoxypropan or pentyloxy or hexyloxy-isomer, preferably a methoxy group, ethoxypropan or n-propoxylate.

Haloalkoxy represents, for example, formatexpr, deformed is xygraph, cryptometer, 2,2,2-triptracker, 1,1,2,2-tetrafluoroethoxy, 2-floridacheap, 2-choreograph or 2,2,2-trichlorethene.

As an example alkenyl radicals can be called vinyl, allyl, methallyl, 1-methylvinyl, but-2-EN-1-yl, pentenyl and 2-hexenyl preferred alkeneamine radicals with a chain length from 3 to 6 carbon atoms.

As an example etkinlik radicals can be called ethinyl, propargyl, 1-methylpropyl, 3-butynyl, but-2-in-1-yl, 2-methylbut-3-in-2-yl, but-3-in-2-yl, 1-pentenyl, Penta-4-in-1-yl and 2-hexenyl, preferred alkynyl by radicals with a chain length from 3 to 6 carbon atoms.

Appropriate haloalkyl radicals are alkeneamine group, one - or multi-substituted with halogen, which, in particular, is bromine or iodine and especially fluorine or chlorine, such as 2 - and 3-forproper, 2 - and 3-chloropropanol, 2 - and 3-bromopropionyl, 2,2-debtor-1-methylvinyl, 2,3,3-triptocaine, 3,3,3-triptocaine, 2,3,3-trichlorpropane, 4,4,4-triflorum-2-EN-1-yl and 4,4,4-trichlorobut-2-EN-1-yl. Preferred alkeneamine radicals, one-, two - or trehkratnye halogen, have a chain length of from 3 to 6 carbon atoms. Alkeneamine group may be substituted with halogen from saturated or unsaturated carbon atoms.

Appropriate haloalkylthio group are, in the example, alkyline group, one - or multi-substituted with halogen, bromine or iodine and especially fluorine or chlorine, for example 3-forproposal, 3-chloropropionyl, 3-bromopropionyl and 4,4,4-triflorum-2-in-1-yl.

Alkenylacyl represents, for example, alliancegroup, metallicakillu or but-2-EN-1-lexigraphy.

Alkyloxy represents, for example, propargyloxy or 1-methylpropyloxy.

Appropriate haloalkoxy are alkenylacyl, one - or multi-substituted with halogen, which is, in particular, bromine or iodine and especially fluorine or chlorine, such as 2 - and 3-forproperty, 2 - and 3-chloropropylamine, 2 - and 3-bromopropylamine, 2,3,3-cryptosporidiosis, 2,3,3-trichlorophenoxy, 4,4,4-triflorum-2-EN-1-lexigraphy and 4,4,4-trichlorobut-2-EN-1-lexigraphy.

Alkoxyalkyl groups have preferably from 1 to 6 carbon atoms. Alkoxyalkyl represents, for example, methoxymethyl, methoxyethyl, ethoxymethyl, ethoxyethyl, n-propoxymethyl, n-propoxyethyl, isopropoxyphenyl or isopropoxide.

Polyalkoxyalkyl represents, for example, methoxyethoxymethyl, ethoxyethoxy, toxicokinetic, n-propoxycarbonyl, isopropoxycarbonyl, methoxyethoxymethyl, amoxilamoxil, this is sitecity, n-propoxycarbonyl, n-propeciaciacil, isopropoxycarbonyl, isopropoxycarbonyl or (ethoxy)3-ethyl.

Appropriate cycloalkyl substituents contain from 3 to 8 carbon atoms and represents, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl. These substituents may be single or multiply substituted with halogen, preferably fluorine, chlorine and/or bromine.

Alkylsulphonyl is primarily acetyl or propionyl. Alkoxycarbonyl represents, for example, methoxycarbonyl, etoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl or isomer of butoxycarbonyl, pentyloxybenzoyl or hexyloxybenzoyl, preferably methoxycarbonyl or etoxycarbonyl.

Phenyl, fenoxaprop and naphthyl may be present in substituted form, thus alternates depending on the specific requirements can be in the ortho, meta and/or para-position, and in the case naftilos ring system is optionally in the 5th, 6th, 7th and/or 8th position. The preferred positions of the substituents are ortho - and para-position relative to the point of attachment of the ring. If the substituents of the phenyl, fenoxaprop and naphthyl not specified explicitly, they are, for example, With1-C4alkyl, halogen, C1-C6haloalkyl, C 1-C6alkoxygroup, C1-C6haloalkoxy, nitrogroup, cyano, amino, C1-C4alkylamino or di(C1-C4alkyl)amino group.

Ancilliary preferably have a chain length of from 1 to 6 carbon atoms. Allylthiourea represents, for example, methylthiourea, ethylthiourea, PropertyGroup, butylthiourea, intelligroup or vexillographer or branched isomer, while the preferred methylthiourea or ethylthiourea.

Haloalkylthio represents, for example, 2,2,2-triptoreline or 2,2,2-trichloracetic.

Alkylsulfonyl represents, for example, methylsulfinyl, ethylsulfinyl, n-propylsulfonyl, isopropylphenyl, n-butylsulfonyl, ISO-butylsulfonyl, second-butylsulfonyl or tert-butylsulfonyl, preferably methylsulfinyl or ethylsulfinyl.

Alkylsulfonyl is, for example, methylsulphonyl, ethylsulfonyl, n-propylsulfonyl, isopropylphenyl, n-butylsulfonyl, ISO-butylsulfonyl, second-butylsulfonyl or tert-butylsulfonyl, preferably methylsulphonyl or ethylsulfonyl.

Alkylamino represents, for example, methylaminopropyl, ethylamino, n-propylamino, isopropylamino or isomer butyl, Pintilie hexylamine.

Di is killingray represents for example, dimethylaminopropyl, methylaminopropyl, diethylaminopropyl, n-propylethylene, dibutylamino or diisopropylamino.

Alkylthiomethyl represents, for example, methylthiomethyl, methylthioethyl, ethylthiomethyl, ethylthioethyl, n-propylthiouracil, n-propylthiouracil, isopropylaminomethyl or isopropylaminoethyl.

Heterocyclyl radicals are preferably 4-8-membered ring containing 1 or 2 heteroatom, such as N, S and/or O. These radicals usually are saturated.

Heteroaryl radicals usually represent a 5 - or 6-membered aromatic heterocycles containing preferably from 1 to 3 heteroatoms, such as N, S and/or O. Examples of relevant heterocyclyl and heteroaryl radicals are pyridyl, pyrrolidyl, piperidyl, pyranyl, dioxane, azetidin, oxetanyl, pyrimidyl, triazinyl, thiazolyl, triazolyl, thiadiazolyl, imidazolyl, oxazolyl, isoxazolyl, pyrazinyl, furyl, thienyl, morpholyl, piperazinil, pyrazolyl, benzoxazolyl, benzothiazolyl, Minoxidil, indolyl and finalyl. Such heterocycles and heteroaromatic radicals may be additionally substituted, the substituents, if they are not specified explicitly, are, for example, halogen, C1-C6alkyl, C1-C6alkoxygroup, C1-C6haloalkyl, C1-C haloalkoxy, C1-C6allylthiourea, amino group, C1-C6alkylamino, di(C1-C6alkyl)amino, phenyl, nitro-group or cyano.

In the above definitions of the substituents expression, according to which "R4and R5together with the nitrogen atoms to which they are attached, form a saturated or unsaturated 5-8-membered heterocyclic ring, which 1) can be interrupted by oxygen, sulfur or the group-NR14and/or may be substituted by halogen, C1-C10the alkyl, C1-C10haloalkyl, hydroxy-group, With1-C6alkoxygroup,1-C6alkoxy-C1-C6alkoxygroup, C1-C6haloalkoxy, mercaptopropyl, C1-C6alkylthiol,3-C7cycloalkyl, heteroaryl, heteroaryl-C1-C6the alkyl, phenyl, phenyl-C1-C6the alkyl or benzyloxy, where the phenyl rings of the last three substituents in turn may be substituted by halogen, C1-C6the alkyl, C1-C6haloalkyl,1-C6alkoxygroup, C1-C6haloalkoxy or nitrogroup, and/or 2) may contain a condensed or spirostanol alkylenes or alkenylamine chain with 2 to 6 carbon atoms, which is optional is positive interrupted by oxygen or sulfur, or at least one ring atom saturated or unsaturated heterocyclic ring forms a bridge connection with this alkalinous or alkenylamine chain"refers, for example, the following heterocyclic ring systems:

In the above polycyclic ring systems group, simplistically represented as a fragmentrepresents a group

5-8-membered heterocyclic ring, which may be formed causesto substituents R4and R5and condensed or spirostane alkylene or alkenylamine chain with chain length from 2 to 6 carbon atoms can be single or multiply interrupted by heteroatoms, such as oxygen.

Values corresponding to the above can also apply to the combined definitions, such as alkoxyalkane, alkylsulfonyl, alkylaminocarbonyl, alkoxycarbonyl, alkylcarboxylic, phenylalkyl, nafcillin and heteroallyl.

Definitions alkylcarboxylic alkylcarboxylic and alkoxycarbonyl carbon atom of the carbonyl group is not included in the lower and upper limits of the content of carbon atoms indicated in each case.

Combo receiver is installed notions which may be specified in respect of the radicals R30, R31and R34present in the Deputy G0the compounds of formula Ia, such as cycloalkylcarbonyl, cycloalkylcarbonyl radical, heterocyclisation radical, heteroarylboronic radical, phenylalkyl radical, finacially radical and heteroepitaxial radical, are derived from concepts that are specified for corresponding substituents in the above-mentioned radicals.

Heterocyclyl radicals preferably contain 1 or 2 heteroatoms, such as N, S and O. They are usually saturated. Heteroaryl radicals are usually aromatic heterocycles, which preferably contain from 1 to 3 heteroatoms, such as N, S and/or O. Such heterocycles and heteroaromatic radicals may be additionally substituted, for example halogen, C1-C4the alkyl and/or amino group. With2-C20alkeneamine groups specified as values of R31may be mono - or polyunsaturated. They contain preferably from 2 to 12, especially from 2 to 6 carbon atoms.

The electrophile G-L formula XII Tsatsa, for example, the following electrophiles: L-C(O)-R30(XIIa), L-C(X1)-X2-R31(IIb), L-(X3)-N(R32)-R33(HS), R32N=C=X3(XIId), L-SO2-R34(He) and L-P(X )(R35)-R36(XIIf).

The electrophile of formula XII L is a leaving group, such as R30C(O)O - or R31O- (where R30and R31have the meanings specified for formula Ia), or a halogen, preferably chlorine, bromine or iodine.

Proposed in the invention method may primarily be used to obtain compounds of the formula I, in which R0in each case independently denotes halogen, C1-C6alkyl, C1-C6haloalkyl, the hydroxy-group, C1-C6alkoxygroup, the nitro-group, an amino group, a C1-C6alkylamino, di(C1-C6alkyl)amino group, a C1-C6alkylcarboxylic, C1-C6alkylsulfonamides, C1-C6alkylaminocarbonyl, C1-C4alkylsulphonyl, C1-C6alkoxycarbonyl or carboxypropyl, a R1, R2and R3each independently of one another denotes hydrogen, halogen, C1-C6alkyl, C1-C6alkenyl,2-C6quinil,3-C6cycloalkyl, C1-C6haloalkyl,2-C6haloalkyl,2-C6haloalkyl,3-C6halachically, C1-C6alkoxy-C1-C6alkyl, C1-C6alkylthio-C1-C6alkyl, cyano, C1-C4alkylsulphonyl, C1-C6 alkoxycarbonyl, the hydroxy-group, C1-C10alkoxygroup,3-C6alkenylacyl,3-C6alkyloxy, C1-C6haloalkoxy,3-C6haloalkylthio, C1-C6alkoxy-C1-C6alkoxygroup, mercaptopropyl, C1-C6allylthiourea, C1-C6haloalkylthio, C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, nitro-group, amino group, With1-C4alkylamino or di(C1-C4alkyl)amino group.

Proposed in the invention method is the most suitable way to obtain the compounds of formula I in which R1, R2and R3each independently of one another denotes hydrogen, halogen, C1-C4alkyl, C2-C4alkenyl,1-C4quinil,1-C4haloalkyl,3- or4-haloalkyl,3-C6cycloalkyl, C1-C4alkylsulphonyl, C1-C6alkoxycarbonyl, the hydroxy-group, With1-C4alkoxygroup,3- or4-alkenylacyl,3- or4-alkyloxy, C1-C4haloalkoxy, the nitro-group or amino group.

In addition, the method according to the invention can also be used to obtain especially those compounds of the formula I,in which R 4and R5together with the nitrogen atom to which they are attached, form a saturated or unsaturated 6 - or 7-membered heterocyclic ring, which 1) may be momentarily interrupted by oxygen or sulphur and/or 2) may contain a condensed or spiritualizing alkylenes chain with 2-5 carbon atoms, which optionally one or twice interrupted by oxygen or sulfur, or at least one ring atom that saturated or unsaturated heterocyclic ring forms a bridge connection with the specified alkalinous chain.

In a preferred embodiment of the proposed method it is advisable to use the compounds of formula II in which R8, R9, R10, R11and R12mean hydrogen, C1-C6alkyl or benzyl.

The process of producing compounds of formulas I and Ia is illustrated in more detail below in reaction schemes 1 and 2.

Reaction scheme 1

Compounds of formulas II and IV, IVa or IVb can be used in equimolar amounts, but more may be preferred to use the compound of formula IV, IVa or IVb in excess of 5 to 50 mol.%.

The reaction of the compound of formula II with the compound of the formula IV, IVa or IVb is carried out at a temperature from 0 to 200°C, preferably from 80 to 150°S./p>

For the interaction of the compounds of the formula II with compounds of formula IV, IVa or IVb suitable such inert organic solvents, such as aromatic, aliphatic and cycloaliphatic hydrocarbons, for example benzene, toluene, isomers of xylene, such as ortho-, meta - and para-xylene, cyclohexane and methylcyclohexane, halogenated hydrocarbons such as chlorobenzene and dichlorobenzene isomers, such as 1,2-, 1,3 - and 1,4-dichlorobenzene, ethers, such as disutility ether, tert-butyl methyl ether, 1,2-dimethoxyethane (DME), dimethyl ether of ethylene glycol, dimethyl ether diethylene glycol, 1,3-dioxolane and dioxane, NITRILES, such as acetonitrile, propionitrile and benzonitrile, diallylsulfide, such as dimethylsulfoxide (DMSO), amides and lactams, for example N,N-dimethylformamide (DMF), N,N-diethylformamide and N-organic (N-MP), alcohols, glycols (diols and polyhydric alcohols, such as propanol, butanol, cyclohexanol, ethylene glycol and 2-ethoxyethanol, as well as in the General case of carboxylic acids, such as acetic acid and propionic acid, or a mixture of such solvents. Preferred organic solvents having a boiling point of which is ≥80°primarily ≥100°C.

The most preferred solvents are toluene, isomers of xylene, such as ortho-, meta - and paraxylene, IU illlogical, chlorobenzene and dichlorobenzene isomers, such as 1,2-, 1,3 - and 1,4-dichlorobenzene.

The reaction according to the invention preferably in an atmosphere of inert gas, such as nitrogen or argon.

The condensation of compounds of the formula II with compounds of formula IV can be accomplished with or without added base. The same condensation with compounds of the formula IVa or IVb (instead of the compounds of formula (IV), it is advisable to carry out in the presence of a base. Suitable for this purpose, the bases are, for example, nitrogenous bases, such as, in particular tertiary amines and pyridine, for example, C1-C6-trialkylamine, Hinkley and 4-dimethylaminopyridine. Other usable for the above purpose bases are, for example, alkali metal alcoholate, in particular methanolate sodium and potassium, ethanolate sodium and potassium tert-butanolate sodium and potassium. You can also use inorganic bases, such as hydrides of alkali and alkaline-earth metals, such as sodium hydride, potassium or calcium hydroxides of alkali and alkaline earth metals such as sodium hydroxide or potassium hydroxide, carbonates of alkali and alkaline earth metals such as sodium carbonate or potassium and bicarbonates of alkali and alkaline earth metals, such as sodium bicarbonate or the Aliya, primarily in the form of solutions in alcohol. This base is used in catalytic quantities, or in a molar excess, amounting to up to 5, in terms of the compound of formula II.

In a preferred embodiment of the proposed method as a reaction medium, in which the dissolved reactants of formulas II and IV, IVa or IVb, using an aromatic hydrocarbon with a boiling point of >80°With, for example xylene. The compound of formula IV, IVa or IVb is preferably used in excess of 5 to 20 mol.% in terms of the compound of formula II. The reaction mixture is heated under reflux for 1-3 hours in an atmosphere of inert gas with or without added base, when used as a compound of the formula IV, and in the presence of organic bases such as triethylamine, taken in equimolar amounts or in excess, which, when using the compounds of formula IVa or IVb may be up to 5 times the equimolar amount. After cooling and addition of diluted acid target product (G means hydrogen) precipitates in the form of a crystalline solid product that can directly filter and wash suitable for this purpose washing agent, such as water and/or hexane.

The compounds of formula I in which R0 , R1, R2, R3, R4, R5and n have the above values, a G means the hydrogen equivalent of a metal ion or an ammonium cation, it is possible in a simple way prevrashat in compounds Ia or

(a) in accordance with the invention directly in the reaction solution in the same reaction vessel without isolation, or

b) in a subsequent reaction stage after highlighting interaction, optionally in the presence of an acid binding agent or catalyst, with an electrophile of formula XII in which G0have the above values, a L is a leaving group, for example R30C(O)O - or R31O- (where R30and R31have the above for formula Ia values) or halogen, preferably chlorine, bromine or iodine. This phase derivatization illustrated in reaction scheme 2.

Reaction scheme 2

Linking acid agents that can be used in the reaction of compounds of formula I with an electrophile of formula XII may be conventional acceptors of protons, for example, hydrides of alkali metals, alcoholate, alkali metal carbonates or bicarbonates of alkali or alkaline earth metals or nitrogenous bases in General, such as triethylamine, Diisopropylamine, pyridine, quinoline, diazabicyclo (DBN) and diazabicyclo the ene (DBU). As catalysts for accelerating the reaction of the compounds of formula I with an electrophile of formula IId, you can add, for example, ORGANOTIN compounds, in particular dilaurate dibutylamine.

As solvents it is possible to use any solvent that is inert towards electrophiles of formula XII and XIIa-XIIf, for example aromatic hydrocarbons, such as benzene, toluene or the isomer of xylene, halogenated hydrocarbons such as dichloromethane, trichloromethane, chlorobenzene or dichlorobenzene isomer, amides such as N,N-dimethylformamide (DMF) or 1-methyl-2-pyrrolidone (N-MP), or ethers, such as disutility ether, 1,2-dimethoxyethane (DME), 1,3-dioxolane, tetrahydrofuran or dioxane.

Similar reaction of compounds of the formula I, in which G denotes hydrogen, corresponding to the above option b), i.e. the reaction is carried out in separate stages, as described, for example, in WO 97/02243 and EP-A 0508126.

The compounds of formula I, which are received proposed in the invention in which G represents the hydrogen equivalent of a metal ion or an ammonium cation, sulfone or phosphonium use so primarily as a source of compounds to obtain the "in situ" of the compounds of the formula Ia, in which G0represents a group-C(O)-R30; -C(X1)-X2-R31With(X3)-N(R32 )-R33, -SO2-R34or-P(X4)(R35)-R36and R30, R31, R32, R33, R34, R35, R36X1, X2, X3and X4have the above for formula Ia values.

The compounds of formula I

in which

R0in each case independently denotes halogen, C1-C6alkyl, C2-C6alkenyl,1-C6quinil, C1-C6haloalkyl, cyano-C1-C6alkyl, C2-C6haloalkyl, cyano-C2-C6alkenyl,1-C6haloalkyl, cyano-C2-C6quinil, the hydroxy-group, hydroxy-C1-C6alkyl, C1-C6alkoxygroup, the nitro-group, amino group, With1-C6alkylamino, di(C1-C6alkyl)amino group, a C1-C6alkylcarboxylic, C1-C6alkylsulfonamides,1-C6alkylaminocarbonyl,1-C6alkylsulphonyl,1-C6alkylsulphonyl-C1-C6alkyl, C1-C6alkoxycarbonyl-C1-C6alkyl, C1-C6alkylsulphonyl-C2-C6alkenyl,1-C6alkoxycarbonyl-C2-C6alkenyl,1-C6alkylsulphonyl-C2-C6quinil,1-C6alkoxycarbonyl-C2-C6 quinil, C1-C6alkoxycarbonyl, cyano, carboxyl, phenyl or aromatic ring containing 1 or 2 heteroatoms selected from the group comprising nitrogen, oxygen and sulphur, the latter two aromatic rings can be substituted C1-C3the alkyl, C1-C3haloalkyl, C1-C3alkoxygroup, C1-C3haloalkoxy, halogen, cyano or nitro-group, or

R0together with the adjacent substituents R1, R2and R3forms a saturated or unsaturated With3-C6hydrocarbon bridge which may be interrupted by 1 or 2 heteroatoms selected from the group comprising nitrogen, oxygen and sulfur, and/or may be substituted With1-C4the alkyl,

R1, R2and R3each independently of one another denotes hydrogen, halogen, C1-C6alkyl, C2-C6alkenyl,2-C6quinil,3-C6cycloalkyl, C1-C6haloalkyl,2-C6haloalkyl,1-C6alkoxycarbonyl-C2-C6alkenyl, C1-C6alkylsulphonyl-C2-C6alkenyl, cyano-C2-C6alkenyl, nitro-C2-C6alkenyl,2-C6haloalkyl,1-C6alkoxycarbonyl-C2-C6quinil, C1-C6alkylsulphonyl-C2/sub> -C6quinil, cyano-C2-C6quinil, nitro-C2-C6quinil,3-C6-halachically, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkylthio-C1-C6alkyl, cyano, C1-C4alkylsulphonyl, C1-C6alkoxycarbonyl, the hydroxy-group, C1-C10alkoxygroup,3-C6alkenylacyl,3-C6alkyloxy, C1-C6haloalkoxy,3-C6haloalkylthio,1-C6alkoxy-C1-C6alkoxygroup, mercaptopropyl, C1-C6allylthiourea, C1-C6haloalkylthio, C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, nitro-group, an amino group, a C1-C6alkylamino, di(C1-C6alkyl)amino group or fenoxaprop, in which the phenyl ring may be substituted C1-C3the alkyl, C1-C3haloalkyl, C1-C3alkoxygroup, C1-C3haloalkoxy, halogen, cyano or nitro-group,

R2can also mean a phenyl, naphthyl or 5 - or 6-membered aromatic ring which may contain 1 or 2 heteroatoms selected from the group comprising nitrogen, oxygen and sulfur, where the phenyl ring, nafti the other

ring system, and 5 - or 6-membered aromatic ring may be substituted with halogen, C3-C8cycloalkyl, hydroxy-group, mercaptopropyl, amino group, cyano, a nitro-group or formyl, and/or phenyl ring, naftalina ring system and 5 - or 6-membered aromatic ring can be substituted C1-C6the alkyl, C1-C6alkoxygroup, hydroxy-C1-C6the alkyl, C1-C6alkoxy-C1-C6the alkyl, C1-C6alkoxy-C1-C6alkoxygroup,1-C6alkylcarboxylic,1-C6alkylthiol,1-C6alkylsulfonyl,1-C6alkylsulfonyl, mono - C1-C6alkylaminocarbonyl, di(C1-C6alkyl)amino group, With1-C6alkylcarboxylic,1-C6alkylsulphonyl(C1-C6alkyl)amino group, With2-C6alkenyl,3-C6alkenylacyl, hydroxy-C3-C6alkenyl, C1-C6alkoxy-C2-C6alkenyl, C1-C6alkoxy-C3-C6alkenylacyl,2-C6alkenylboronic,2-C6alkenylsilanes,2-C6alkanesulfonyl,2-C6alkanesulfonyl, mono - or di-(C2-C6alkenyl)amino group is th, With1-C6alkyl(C3-C6alkenyl)amino group, With2-C6alkenylamine,2-C6alkenylboronic(C1-C6alkyl)amino group, With2-C6the quinil,3-C6alkyloxy, hydroxy-C3-C6the quinil, C1-C6alkoxy-C3-C6the quinil, C1-C6alkoxy-C4-C6alkynylamino,2-C6alkylammonium,2-C6alkylalcohol,2-C6alkylsulfonyl,2-C6alkylsulfonyl, mono - or di-(C3-C6quinil)amino group, a C1-C6alkyl(C3-C6quinil)amino group, With2-C6alkylcarboxylic or2-C6alkenylboronic(C1-C6alkyl)amino group and/or phenyl ring, naftalina ring system and 5 - or 6-membered aromatic ring may be substituted with halogen substituted C1-C6the alkyl, C1-C6alkoxygroup, hydroxy-C1-C6the alkyl, C1-C6alkoxy-C1-C6the alkyl, C1-C6alkoxy-C1-C6alkoxygroup,1-C6alkylcarboxylic,1-C6alkylthiol,1-C6alkylsulfonyl,1-C6alkylsulfonyl, mono-C1-sub> 6alkylaminocarbonyl, di(C1-C6alkyl)amino group, a C1-C6alkylcarboxylic,1-C6alkylsulphonyl(C1-C6alkyl)amino group, With2-C6alkenyl,3-C6alkenylacyl, hydroxy-C3-C6alkenyl,1-C6alkoxy-C2-C6alkenyl, C1-C6alkoxy-C3-C6alkenylacyl,2-C6alkenylboronic,2-C6alkenylsilanes,2-C6alkanesulfonyl,2-C6alkanesulfonyl, mono - or di-(C2-C6alkenyl)amino group, With1-C6alkyl-(C3-C6alkenyl)amino group, With2-C6alkenylamine,2-C6alkenylboronic(C1-C6alkyl)amino group, With3-C6the quinil,3-C6alkyloxy, hydroxy-C3-C6the quinil, C1-C6alkoxy-C3-C6the quinil,1-C6alkoxy-C4-C6alkynylamino,2-C6alkylammonium,2-C6alkylalcohol,2-C6alkylsulfonyl,2-C6alkylsulfonyl, mono - or di-(C3-C6quinil)amino group, With1-C6alkyl(C3-C6quinil)amino group, With2-C alkylcarboxylic or2-C6alkenylboronic(C1-C6alkyl)amino group and/or phenyl ring, naftalina ring system and 5 - or 6-membered aromatic ring may be substituted by a radical of the formula COOR50,CONR51, S02NR53R54or SO2OR55where R50, R51, R52, R53, R54and R55each independently from each other mean C1-C6alkyl, C2-C6alkenyl or3-C6quinil or substituted with halogen, hydroxy-group, alkoxygroup, mercaptopropyl, amino group, cyano, a nitro-group, alkylthiol, alkylsulfonyl or alkylsulfonyl C1-C6alkyl, C2-C6alkenyl or3-C6quinil,

n denotes 1 or 2,

R4and R5together with the nitrogen atoms to which they are attached, form a saturated or unsaturated 5-8-membered heterocyclic ring, which 1) is interrupted by oxygen, sulfur or the group-NR14and may be replaced

halogen, C1-C10the alkyl, C1-C10haloalkyl, hydroxy-group, With1-C6alkoxygroup,1-C6alkoxy-C1-C6alkoxygroup,1-C6haloalkoxy, mercaptopropyl, C1-C6alkylthiol,3-C7cyclol the sludge, heteroaryl, heteroaryl-C1-C6the alkyl, phenyl, phenyl-C1-C6the alkyl or benzyloxy, where the phenyl rings of the last three substituents in turn may be substituted by halogen, C1-C6the alkyl, C1-C6haloalkyl, C1-C6alkoxygroup, C1-C6haloalkoxy or nitrogroup, and 2) may contain a condensed or spirostanol alkylenes or alkenylamine chain with 2 to 6 carbon atoms, which is optionally interrupted by oxygen or sulfur, or at least one ring atom saturated or unsaturated heterocyclic ring forms a bridge connection with this alkalinous or alkenylamine circuit, with R14means hydrogen, C1-C4alkyl, C1-C6alkylsulphonyl, C1-C6alkylsulfonyl, C3-C6alkenyl or3-C6quinil,and

G means the hydrogen equivalent of a metal ion or an ammonium cation, sulfone or phosphonium, are new compounds. Thus, the invention relates also to these compounds.

The compounds of formula Ia

in which R0in each case independently denotes halogen, C1-C6alkyl, C2-C6alkenyl,2-C6quinil, C1-C6haloalkyl, cyan is-C 1-C6alkyl, C2-C6haloalkyl, cyano-C2-C6alkenyl,2-C6haloalkyl, cyano-C2-C6quinil, the hydroxy-group, hydroxy-C1-C6alkyl, C1-C6alkoxygroup, the nitro-group, an amino group, a C1-C6alkylamino, di(C1-C6alkyl)amino group, a C1-C6alkylcarboxylic, C1-C6alkylsulfonamides, C1-C6alkylaminocarbonyl, C1-C6alkylsulphonyl,1-C6alkylsulphonyl-C1-C6alkyl, C1-C6alkoxycarbonyl-C1-C6alkyl, C1-C6alkylsulphonyl-C2-C6alkenyl,1-C6alkoxycarbonyl-C2-C6alkenyl,1-C6alkylsulphonyl-C2-C6quinil,1-C6alkoxycarbonyl-C2-C6quinil, C1-C6alkoxycarbonyl, cyano, carboxyl, phenyl or aromatic ring containing 1 or 2 heteroatoms selected from the group comprising nitrogen, oxygen and sulfur, while the last two aromatic rings can be substituted C1-C3the alkyl, C1-C3haloalkyl, C1-C3alkoxygroup, C1-C3haloalkoxy, halogen, cyano or nitro-group, or R0together with the adjacent substituent and R 1, R2and R3, forms a saturated or unsaturated With3-C6hydrocarbon bridge which may be interrupted by 1 or 2 heteroatoms selected from the group comprising nitrogen, oxygen and sulfur, and/or may be substituted With1-C4the alkyl, R1, R2and R3each independently of one another denotes hydrogen, halogen, C1-C6alkyl, C2-C6alkenyl,2-C6quinil,3-C6cycloalkyl, C1-C6haloalkyl,2-C6haloalkyl,1-C6alkoxycarbonyl-C2-C6alkenyl,1-C6alkylsulphonyl-C2-C6alkenyl, cyano-C2-C6alkenyl, nitro-C2-C6alkenyl,2-C6haloalkyl,1-C6alkoxycarbonyl-C2-C6quinil, C1-C6alkylsulphonyl-C2-C6quinil, cyano-C2-C6quinil, nitro-C2-C6quinil,3-C6halachically, hydroxy-C1-C6alkyl, C1-C6alkoxy-C1-C6alkyl, C1-C6alkylthio-C1-C6alkyl, cyano, C1-C4alkylsulphonyl, C1-C6alkoxycarbonyl, the hydroxy-group, C1-C10alkoxygroup,3-C6alkenylacyl,3-C6alkyloxy, C1-C6 haloalkoxy,3-C6haloalkylthio,1-C6alkoxy-C1-C6alkoxygroup, mercaptopropyl, C1-C6allylthiourea, C1-C6haloalkylthio, C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, nitro-group, an amino group, a C1-C6alkylamino, di(C1-C6alkyl)amino group or fenoxaprop, where the phenyl ring may be substituted C1-C3the alkyl, C1-C3haloalkyl,

C1-C3alkoxygroup, C1-C3haloalkoxy, halogen, cyano or nitro-group,

R2can also mean a phenyl, naphthyl or 5 - or 6-membered aromatic ring which may contain 1 or 2 heteroatoms selected from the group comprising nitrogen, oxygen and sulfur, with the phenyl ring, naftalina ring system and 5 - or 6-membered aromatic ring may be substituted with halogen, C3-C8cycloalkyl, hydroxy-group, mercaptopropyl, amino group, cyano, a nitro-group or formyl, and/or phenyl ring, naftalina ring system and 5 - or 6-membered aromatic ring can be substituted C1-C6the alkyl, C1-C6alkoxygroup, hydroxy-C1-C6the alkyl, C1-C6alkoxy-C1-C6the alkyl,C 1-C6alkoxy-C1-C6alkoxygroup, C1-C6alkylcarboxylic, C1-C6alkylthiol, C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, mono-C1-C6alkylaminocarbonyl, di(C1-C6alkyl)amino group, a C1-C6alkylcarboxylic, C1-C6alkylsulphonyl(C1-C6alkyl)amino group, With2-C6alkenyl,3-C6alkenylacyl, hydroxy-C3-C6alkenyl, C1-C6alkoxy-C2-C6alkenyl, C1-C6alkoxy-C3-C6alkenylacyl,2-C6alkenylboronic,2-C6alkenylsilanes, C2-C6alkanesulfonyl,2-C6alkanesulfonyl, mono - or di-(C2-C6alkenyl)amino group, a C1-C6alkyl(C3-C6alkenyl)amino group, With2-C6alkenylamine,2-C6alkenylboronic(C1-C6alkyl)amino group, With2-C6the quinil,3-C6alkyloxy, hydroxy-C3-C6the quinil, C1-C6alkoxy-C3-C6the quinil, C1-C6alkoxy-C4-C6alkynylamino,2-C6alkylammonium, C2-C6alkylthio is, With2-C6alkylsulfonyl, C2-C6alkylsulfonyl, mono - or di-(C3-C6quinil)amino group, a C1-C6alkyl(C3-C6quinil)amino group, With2-C6alkylcarboxylic or2-C6alkenylboronic(C1-C6alkyl)amino group and/or phenyl ring, naftalina ring system and 5 - or 6-membered aromatic ring may be substituted with halogen substituted C1-C6the alkyl, C1-C6alkoxygroup, hydroxy-C1-C6the alkyl, C1-C6alkoxy-C1-C6the alkyl, C1-C6alkoxy-C1-C6alkoxygroup, C1-C6alkylcarboxylic, C1-C6alkylthiol, C1-C6alkylsulfonyl, C1-C6alkylsulfonyl, mono - C1-C6alkylaminocarbonyl, di(C1-C6alkyl)amino group, a C1-C6alkylcarboxylic, C1-C6alkylsulphonyl(C1-C6alkyl)amino group, With2-C6alkenyl,3-C6alkenylacyl, hydroxy-C3-C6alkenyl, C1-C6alkoxy-C2-C6alkenyl, C1-C6alkoxy-C3-C6alkenylacyl,2-C6alkenylboronic,2-C6alkenylsilanes,2-C 6alkanesulfonyl,2-C6alkanesulfonyl, mono - or di-(C2-C6alkenyl)amino group, a C1-C6alkyl-(C3-C6alkenyl)amino group, With2-C6alkenylamine,2-C6alkenylboronic(C1-C6alkyl)amino group, With2-C6the quinil,3-C6alkyloxy, hydroxy-C3-C6the quinil, C1-C6alkoxy-C3-C6the quinil, C1-C6alkoxy-C4-C6alkynylamino,2-C6alkylammonium,2-C6alkylalcohol,2-C6alkylsulfonyl,2-C6alkylsulfonyl, mono - or di-(C3-C6quinil)amino group, a C1-C6alkyl(C3-C6quinil)amino group, With2-C6alkylcarboxylic or2-C6alkenylboronic(C1-C6alkyl)amino group and/or phenyl ring, naftalina ring system and 5 - or 6-membered aromatic ring may be substituted by a radical of the formula COOR50, CONR51, SO2NR53R54or SO2OR55where R50, R51, R52, R53, R54and R55each independently from each other mean C1-C6alkyl, C2-C6alkenyl or3-C6Alki the sludge or substituted with halogen, hydroxy-group, alkoxygroup, mercaptopropyl, amino group, cyano, a nitro-group, alkylthiol, alkylsulfonyl or alkylsulfonyl C1-C6alkyl, C2-C6alkenyl or3-C6quinil,

n denotes 1 or 2,

R4and R5together with the nitrogen atoms to which they are attached, form a saturated or unsaturated 5-8-membered heterocyclic ring, which 1) is interrupted by oxygen, sulfur or the group-NR14and may be substituted with halogen, C1-C10the alkyl, C1-C10haloalkyl, hydroxy-group, C1-C6alkoxygroup,1-C6alkoxy-C1-C6alkoxygroup, C1-C6haloalkoxy, mercaptopropyl, C1-C6alkylthiol,3-C7cycloalkyl, heteroaryl, heteroaryl - C1-C6the alkyl, phenyl, phenyl-C1-C6the alkyl or benzyloxy, where the phenyl rings of the last three substituents in turn may be substituted by halogen, C1-C6the alkyl, C1-C6haloalkyl, C1-C6alkoxygroup, C1-C6haloalkoxy or nitrogroup, and 2) may contain a condensed or spirostanol alkylenes or alkenylamine chain with 2 to 6 carbon atoms, which is optionally interrupted by oxygen or the hero, or at least one ring atom saturated or unsaturated heterocyclic ring bridge connection with this alkalinous or alkenylamine circuit, with R14means hydrogen, C1-C4alkyl, C1-C6alkylsulphonyl, C1-C6alkylsulfonyl, C3-C6alkenyl or3-C6quinil, and

G0means the group-C(O)-R30, -C(X1)-X2-R31or-SO2-R34where

X1, X2, X3and X4each independently of one another denotes oxygen or sulfur, R30means unsubstituted or substituted with halogen With1-C20alkyl, C2-C20alkenyl,1-C8alkoxy-C1-C8alkyl, C1-C8alkylthio-C1-C8alkyl, poly - C1-C8alkoxy-C1-C8alkyl or unsubstituted or substituted with halogen With3-C8cycloalkyl,3-C6cycloalkyl-C1-C6alkyl, heterocyclyl-C1-C6alkyl, heteroaryl-C1-C6alkyl, unsubstituted or substituted with halogen, a cyano, a nitro-group, With1-C6the alkyl, C1-C6alkoxygroup,1-C6haloalkyl,1-C6haloalkoxy,1-C6alkylthiophene or1-C6alkylsulfonyl phenyl, Nezami the military or substituted with halogen, nitrogroup, cyano, C1-C6the alkyl, C1-C6alkoxygroup,

With1-C6haloalkyl or1-C6haloalkoxy phenyl-C1-C6alkyl, unsubstituted or substituted with halogen or1-C6the alkyl heteroaryl, unsubstituted or substituted with halogen or1-C6the alkyl, phenoxy-C1-C6alkyl or unsubstituted or substituted by halogen, amino or1-C6the alkyl, heteroaromatic-C1-C6alkyl, R31means unsubstituted or substituted with halogen With1-C20alkyl, C2-C20alkenyl,1-C8alkoxy-C2-C8alkyl, poly-C1-C8alkoxy-C2-C8alkyl, unsubstituted or substituted with halogen or C1-C6alkoxygroup3-C8cycloalkyl,3-C6cycloalkyl-C1-C6alkyl, heterocyclyl-C1-C6alkyl, heteroaryl-C1-C6alkyl, unsubstituted or substituted with halogen, a cyano, a nitro-group, C1-C6the alkyl, C1-C6alkoxygroup, C1-C6haloalkyl or C1-C6haloalkoxy phenyl or benzyl and R34means unsubstituted or substituted with halogen With1-C8alkyl or unsubstituted or substituted with halogen, 1-C6the alkyl, C1-C6alkoxygroup,1-C4haloalkyl,1-C4haloalkoxy, cyano group or nitro-group is phenyl,

are new compounds. Thus, the invention relates also to these compounds.

The compounds of formula II

in which R0, R1, R2, R3, R6, R7and n have the abovementioned meanings, are novel and were developed specifically for the proposed in the invention method. The invention relates accordingly to these compounds.

Preferred are those compounds of formula II in which R1, R2and R3each independently of one another denotes hydrogen, halogen, C1-C4alkyl, C1-C4haloalkyl,2-C4alkenyl,2-C4haloalkyl,2-C4quinil,3-C6cycloalkyl,1-C4alkylsulphonyl, C1-C6alkoxycarbonyl, the hydroxy-group, With1-C4alkoxygroup,3- or4-alkenylacyl,3- or4-alkyloxy,1-C4haloalkoxy, the nitro-group or amino group.

Preferred further compounds of formula II in which R1means2-C6alkyl.

Equally preferred connection is of formula II, in which n is equal to 0.

Among the above compounds of formula II are particularly preferred compounds in which R1means2-C4alkyl, C1-C4alkoxygroup,2-C4quinil or3-C6cycloalkyl, and R3means1-C4alkyl, C1-C4alkoxygroup,2-C4quinil or3-C6cycloalkyl.

Preferred are also the compounds of formula II in which R1means2-C6quinil.

In addition are preferred connection of the formula II in which R1and R3each independently from each other mean With2-C6alkyl, C2-C6quinil, C1-C10alkoxygroup or3-C6cycloalkyl. Among these compounds, particularly preferred compounds in which R1means2-C6alkyl, and R3means2-C6alkyl, C2-C6quinil or C1-C10alkoxygroup.

Important are also the compounds of formula II in which R6represents a group R8R9N-, R7means the group R10R11N, a R8, R9, R10and R11have the above for formula II.

The compounds of formula IIA

in which R0, R1, R2 , R3and n have the above for formula I values, a R8, R9, R10and R11mean hydrogen, can be obtained, for example, directly from the relevant dinitriles phenylmalonate acid of formula VI

in which R0, R1, R2, R3and n have the above meanings, by hydrolysis. As gidroliznaya agents you can use concentrated mineral acid, such as sulfuric acid or nitric acid, optionally with the addition of water.

The process of producing compounds of the formula IIA

in which R0, R1, R2, R3and n have the above for formula I values, a R8, R9, R10and R11each independently of one another denotes hydrogen, C1-C6alkyl, C1-C6haloalkyl,3-C6alkenyl or benzyl, where the phenyl ring of the benzyl group may be substituted With1-C4by alkyl, halogen, C1-C4haloalkyl, C1-C4alkoxygroup or nitrogroup, may, for example, concluded that:

1) phenylacetamide formula VII

in which R0, R1, R2, R3, R8, R9and n have the above meanings, or

a) put the cos is deystviy with the isocyanate of formula XI

in which R10have the above values, except for hydrogen, this reaction does not necessarily catalyze the substrate and is carried out in an inert reaction medium (R11means of hydrogen in the compound of formula IIA), or

b) is subjected to interaction at a temperature of distillation with a carbonate of formula XIV

in which R12means C1-C6alkyl, C1-C6haloalkyl,3-C6alkenyl or benzyl, where the phenyl ring of the benzyl group may be substituted With1-C4by alkyl, halogen, C1-C4haloalkyl,1-C4alkoxygroup or nitrogroup, receiving a first compound of the formula IIb

in which R0, R1, R2, R3, R8, R9, R12and n have the above meanings, and then this compound is subjected to interaction in an inert solvent with an amine of the formula X

in which R10and R11have the above values, or

2) ester of phenylacetic acid of the formula VIII

in which R0, R1, R2, R3, R12and n have the above meanings, or

C) is subjected to interaction with the isocyanate of formula XV

in which R8have the above values, except for hydrogen, this reaction does not necessarily catalyze the substrate and is carried out in an inert reaction medium, receiving a first compound of the formula IIb

in which R0, R1, R2, R3, R8, R12and n have the above values, a R9means hydrogen, and then this compound as described in claim 1)

b) is subjected to interaction in an inert solvent with an amine of the formula X, or

g) when subjected to an elevated temperature interaction with carbonate of the formula XVI

in which R13has the same meaning as R12receiving the first diperpanjang acid of the formula III

in which R0, R1, R2, R3, R12, R13and n have the above meanings, and then this compound as described in claim 1)

b) the methodology exposed in an inert solvent interaction with the amine of the formula IX or X

where R8, R9, R10and R11have the above values.

The above options are illustrated in reaction scheme 3.

Reaction scheme 3

Diamides phenylmalonate acid of formula IIA can be obtained according to reaction scheme 3 (option a) in accordance with known procedures from phenylacetamido formula VII using isocyanates of the formula XI, the reaction does not necessarily catalyze the substrate and is carried out in an inert solvent.

According to reaction scheme 3 (b), the diamide phenylmalonate acid of the formula IIA can also be obtained from phenylacetamido formula VII by heating under reflux for several hours in the carbonates of the formula XIV as solvents, receiving first the compounds of formula IIb, followed by amidation in the solvent using amines of the formula X. a Similar reaction with the ether derivative of phenylacetic acid and carbonates of the formula XVI are described, for example, in WO 97/02243.

Other alternative processes for the diamide phenylmalonate acid of formula IIA based on esters of phenylacetic acid of the formula VIII are according to reaction scheme 3 the following two options: option) the compounds of formula VIII can, for example, initially be subjected to a similar Tetpahedron Lett. 1974, 2427, interaction with isocyanates of the formula XV by catalyzing the reaction of the substrate and carrying out the reaction in an inert reaction medium, to obtain the compounds of formula IIb (R9means hydrogen), which is s then lidiruyut in an inert solvent, similarly to variant b) with amines of the formula X, or in accordance with option (d) compounds of formula VIII can, for example, initially be interaction at the temperature of distillation in carbonates of the formula XVI as solvents to obtain the diesters phenylmalonate acid of the formula III, which are then lidiruyut in a solvent similar to option b) using amines of the formula IX or X.

Compounds of formula IV, IV and IVb are either known compounds or they can be obtained by known methods. Methods for obtaining compounds of formula IV are described, for example, in WO 95/00521 and PCT/ER/01593.

Dinitrile derivatives of phenylmalonate acid of formula VI are either known compounds or they can be obtained by known methods described, for example, in Chem. Commun. 1984, 932, or in J. Am. Chem. Soc. 121, 1473(1999).

Phenylacetamide and esters of phenylacetic acid of formula VII and VIII are known compounds. Esters of phenylacetic acid of the formula VIII is described, for example, in WO 97/02243.

The reagents of formulas IX, X, XI, XII and Ha, XIIb, XIIc, XIId, XIIe and XIIf, XIV, XV and XVI, used in the reactions according to reaction schemes 1, 2 and 3, respectively, are either known compounds or they can be obtained by known methods.

Proposed in the invention the method is characterized by:

a) easily accessible starting compounds of formula II,

b) ease of implementation reactions and pererabotki is,

in General, high yield,

g) economic and environmental benefits of the process carried out in one reaction vessel, in respect of subsequent derivatization of compounds of formula I to obtain the compounds of formula Ia (for example, when turning the substituent G in the G0and

d) the economic and environmental advantages due to the possibility to carry out a particular stage of the method, namely the initial formation of compounds of formula II (reaction scheme 3), their subsequent interaction with compounds of formula IV, IVa or IVb with obtaining compounds of formula I (reaction scheme 1) and then their interaction with electrophiles of formula XII, Ha, IIb, HS or XIId in the form of a continuous reaction with formation of compounds of formula Ia.

Proposed in the invention method is suitable primarily for industrial scale of 4-aryl-5-oxadiazoline derivatives of formulas I and Ia.

Below proposed in the invention method is illustrated in the examples which do not limit the scope of the invention.

Examples retrieve

Example P1: Getting diamide 2,4,6-trimethylphenylsulfonyl acid

A solution of 2.0 g (0,0109 mole) of dinitrile 2,4,6-trimethylphenylsulfonyl acid in 5 ml of dichloromethane for 2 min is added dropwise to a mixture of 5 ml kontsentrirovannymi acid (97%) and 0.4 ml (0,022 mol) of water. After stirring for 100 h at 20°the reaction mixture was poured onto ice and extracted twice with ethyl acetate. The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo at 60°C. Thus obtain 2.0 g (83% of theory) of the target specified in the connection header in the form of yellowish crystals of tPL177-179°C.

Example P2: Getting diamide 2,6-diethyl-4-methylphenylimino acid

2.1 g (0,0099 mole) of dinitrile 2,6-diethyl-4-methylphenylimino acid is added to a mixture of 5 ml of concentrated sulfuric acid (97%) and 0.36 ml (0,0198 mole) of water. After stirring for 5 min at 50°is formed With a homogeneous red color solution, which is stirred for 5 h at 50°C. Then the reaction mixture was cooled to 22°and then poured into a mixture of ice and water. After double extraction with ethyl acetate the combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo at 60°C. Thus obtain 2.35 g (95.6% of theory) of the target specified in the title compound as yellowish crystals with tPL184-186°C.

1H-NMR (CDCl3): 7,19 frequent./million (broad s, 1H), 6,99 frequent./million (s, 2H), 5,78 frequent./million (s, 1H), 4,69 frequent./million (s, 1H), 2,55 frequent./m (q, 4H), 2,32 frequent./million (s, MN), 1,21 frequent./m (t, 6H).

Example P3: Obtain 8-(2,4,6-trimetilfenil)tetrahydropyrazolo[1,2-d|[1,4,5]oxadiazine-7,9-dione

A solution of 1.5 g (0,0068 mole) of diamide 2,4,6-trimethylphenylsulfonyl acid, 2.16 g (0,0082 mole) of dihydrobromide [1,4,5]oxadiazine and 2.93 g (0,029 mole) of triethylamine in 50 ml of xylene for two hours, heated under reflux in a nitrogen atmosphere. The resulting suspension is cooled to 22°C, mixed with 1H. hydrochloric acid and filtered. The crystalline residue is washed with water then diethyl ether and then dried in vacuum at 60°S. This way get the target specified in the header of the connection with tPL248-250°C.

Example P4: Obtain 8-(2,6-diethyl-4-were)tetrahydropyrazolo[1,2-d][1,4,5]oxadiazine-7,9-dione

A solution of 2.15 g (0,00866 mole) of diamide 2,6-diethyl-4-methylphenylimino acid, 2.64 g (0,010 mol) of dihydrobromide [1,4,5]oxadiazine and of 3.54 g (or 0.035 mole) of triethylamine in 50 ml of xylene for 2 hours and heated under reflux in a nitrogen atmosphere. The resulting suspension is cooled to 22°add 50 ml of 1N. hydrochloric acid and the mixture is stirred for 5 minutes After adding 50 ml of hexane resulting solid is filtered off, washed sky is isim amount of water and hexane and dried in vacuum at 80° C. in This way obtain 2.15 g of the target specified in the title compounds as colorless solids with tPL193-194°C. the Organic phase is dried over sodium sulfate and concentrated in vacuo at 60°receiving additional 0,23 g specified in the connection header. The total yield of product is 2.38 g (87% of theory).

1H-NMR (CDCl3): 6,92 frequent./m (d, 2H), 4.72 in part./million (s, 1H), 4,30 frequent./million (m, 2H), 3,98 frequent./million (m, 4H), 3,79 frequent./million (m, 2H), 2,80 frequent./million (s, 3H), 2,70 frequent./m (q, 2H), 2,27 frequent./m (q, 2H), 1,27 frequent./m (t, 3H), 1,20 frequent./m (t, 3H).

Example P5: Obtain 8-(2,6-diethyl-4-were)tetrahydropyrazolo[1,2-d][1,4,5]oxadiazine-7,9-dione

A solution of 0.55 g (0,002 mol) of 2-(2,6-diethyl-4-were)-N,N’-dimethylacetamide, 0,42 g (0,0024 mole) of dihydrobromide [1,4,5]oxadiazine and at 1.17 ml (0,0084 mole) of triethylamine in 6 ml of xylene for 18 h heated under reflux in a nitrogen atmosphere. Then the reaction mixture is poured into water, the mixture acidified with 2n. hydrochloric acid and the suspension is stirred with hexane. The solid is filtered off, washed with water and hexane and dried in vacuum at 50°C. Thus obtain 0.33 g of the target specified in the connection header in the form of beige crystals with tPL192-193,5°C.

Example P6: Obtain 8-(2,6-diethyl-4-were)-9-oxo-1,2,4,5-tetrahydro-N-pyrazolo[,2-d][1,4,5]oxadiazine-7-silt ether of 2,2-dimethylpropionic acid in one reaction vessel

A solution of 1.0 g (0,004 mol) diamide 2,6-diethyl-4-methylphenylimino acid, 0.84 g (0,0048 mole) of dihydrobromide [1,4,5]oxadiazine and of 1.62 g (to 0.016 mole) of triethylamine in 25 ml of xylene for 2 hours and heated under reflux in a nitrogen atmosphere. Then the reaction mixture is cooled to room temperature, add 0.87 g (0,0072 mole) of pivaloyloxy and the mixture is stirred for 2 h at 22°C. After that the reaction mixture is stirred with 25 ml of 1N. hydrochloric acid and extracted with ethyl acetate. The organic extracts are washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated in vacuo at 60°C. Thus obtain 2.3 g of a brown oil. After recrystallization from hexane obtain 1.0 g of the target specified in the title compounds as colorless crystals with tPL120-122°C.

1H-NMR (Dl3): 6,89 frequent./million (s, 2H), 4,29 frequent./million (m, 2H), 3.95 to frequent./million (m, 2H), a 3.87 frequent./million (m, 4H), 2,49 frequent./million (m, 4H), 2,30 frequent./million (s, MN), 1,12 frequent./m (t, 6N), 1,04 frequent./million (s, 9H).

Example P7: Obtain 2-(2,6-diethyl-4-were)-N,N’-dimethylacetamide

30 ml of 33%solution of methylamine in ethanol at 22°add to 4,18 g (0,015 mol) dimethyl 2-(2,6-diethyl-4-were)of malonic acid and the mixture is stirred at 75°in accordance With their 30 PM Then the reaction mixture is poured into water, acidified with conc. hydrochloric acid and extracted with simple ether. The organic extracts are washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated in vacuo at 60°C. the resulting residue (4.0 g of brown oil) was stirred with hexane, receiving of 1.74 g of the target specified in the connection header in the form of a crystalline product with tPL98-100°C.

Example P8: Obtain 2-(2,4,6-trimetilfenil)tetrahydropyrazolo[1,2-a]pyridazine-1,3-dione (without addition of base)

A solution of 2.05 g (0,0093 mole) of diamide 2,4,6-trimethylphenylsulfonyl acid and 0.95 g (0,0110 mole) hexahydropyridine in 50 ml of xylene for 2 hours and refluxed in a nitrogen atmosphere. Then the reaction mixture was cooled to 22°C and stirred with 50 ml of 1N. hydrochloric acid, after which the resulting suspension is filtered and the crystalline residue is washed first with diethyl ether and then with water and dried in vacuum. This way obtain 2.2 g of the target specified in the title compounds as colorless crystals with tPL247-248°C.

1H-NMR (CDCl3): 6,93 frequent./million (s, 1H), 6,83 frequent./million (s, 1H), 4,65 frequent./million (s, 1H), 3,67 frequent./million (broad s, 4H), 2.40 a part./million (s, 3H), 2,27 frequent./million (s, 3H), 2,04 frequent./million (s, 3H), 1,83 frequent./million (broad s, 4).

Example P9: Getting diamide 2,6-diethyl-4-(4-pyridyl)phenylmalonate acid

36 mg (0,002 mol) of water, and then 360 mg (about 75%, about 0.001 mole) of dinitrile 2,6-diethyl-4-(4-pyridyl)phenylmalonate acid is added to 0.5 ml of sulfuric acid (97%) and the mixture was stirred at 50°for 5.5 h the Cooled reaction mixture is neutralized with saturated sodium hydrogen carbonate solution, the precipitate is filtered off and washed with water, after which the crystals are suspended in a small amount of diethyl ether, filtered and dried. In this way receive 145 mg (47% of theory) of the target specified in the connection header with tPL184-186°C.

1H-NMR (Dl3): 8,63 frequent./m (d, 2H), of 7.48 frequent./m (d, 2H), 7,40 frequent./million (s, 2H), 7,20 frequent./million (broad signal, 2H), 5,81 frequent./million (broad signal, 2H), 4.80 to frequent./million (s, 1H), 2,68 frequent./m (q, 4H), 1,30 frequent./m (t, 6H).

Example P10: Diamid 2,6-diethyl-4-(2-pyridyl)phenylmalonate acid

Specified in the header of the connection get similar to the previous example.

tPL230°C (decomposition).

1H-NMR (CDCl3): 8,68 frequent./m (d, 1H), 4,66-7,80 frequent./million (m, 4H), 7.23 percent frequent./million (m, 1H), 7,20 frequent./million (Shiroki signal, 2H), 5,67 frequent./million (broad signal, 2H), 4.80 to frequent./million (s, 1H), 2,67 frequent./m (q, 4H), 1,30 frequent./m (t, 6N).

Example P11: Obtain 8-(2,6-diethyl-2-pyridine-4-ylphenyl)-9-oxo-,2,4,5-tetrahydro-N-pyrazolo[1,2-d][1,4,5]oxadiazine-7-silt ether of 2,2-dimethylpropionic acid

290 mg (0,0011 mole) of dihydrobromide [1,4,5]oxadiazine and 0.56 ml (0,004 mol) of triethylamine are added to 7 ml of degassed xylene, and then add 311 mg (0,001 mol) diamide 2,6-diethyl-4-(2-pyridyl)phenylmalonate acid and the mixture is stirred at 150°C for 4 h, the Reaction mixture is left to stand overnight at 20°, then cooled to a temperature in the range from 0 to 5°With, then added dropwise is 0.135 ml (0,0011 mole) of the acid chloride pavlinovoi acid. The mixture to complete the reaction is stirred for 3 h at 20°C, then poured into a mixture of ice water and extracted twice with ethyl acetate. The combined organic phases are washed with water and brine, dried over sodium sulfate and concentrated. The crude product weighing 345 mg (75% of theory) crystallized from diethyl ether. In this way receive 160 mg target specified in the title compound (35% of theory) with tPL146-147°C.

1H-NMR (CDCl3): 8,70 frequent./million (m, 1H), 7,72 frequent./million (m, 2H), 7,70 frequent./million (s, 2H), 7,22 frequent./million (m, 1H), 4,30 frequent./million (m, 2H), 3,97 frequent./million (m, 2H), 3,89 frequent./million (m, 4H), 2,62 frequent./million (m, 4H), 1,21 frequent./m (t, 6H), 1,03 frequent./million (s, 9H).

Example R: 8-(2,6-diethyl-4-pyridin-4-ylphenyl)-9-oxo-1,2,4,5-tetrahydro-N.-pyrazolo[1,2-d][1,4,5]oxadiazine-7-silt ether of 2,2-dimethylpropionic acid

Specified in the header of the connection which are square-similar to the previous example.

1H-NMR (CDCl3): 8,19 frequent./million (broad signal, 2H), 7,53 frequent./million (broad signal, 2H), 7,35 frequent./million (s, 2H), 4,30 frequent./million (m, 2H), 3.96 points frequent./million (m, 2H), 3,89 frequent./million (m, 4H), 2,62 frequent./million (m, 4H), 1,20 frequent./m (t, 6H), 1.05 is frequent./million (s, 9H).

1. The method of obtaining the compounds of formula I

in which

R1, R2and R3each independently from each other mean C1-C6alkyl,

R2may also represent a pyridyl,

R4and R5together with the nitrogen atoms to which they are attached, form a saturated 5-8 membered heterocyclic ring which may be interrupted by oxygen, and

G denotes hydrogen,

namely, the compound of formula II

in which R1, R2and R3have the above values, R6means the group R8R9N-, R7means the group R10R11N-, and R8, R9, R10, R11each independently of one another denotes hydrogen or C1-C6alkyl, are subjected to interaction in an inert organic solvent, optionally in the presence of a base, with a compound of formula IV, IVa or IVb

or

in which R4and R5have the above values, and N·l means a hydrogen halide, and the resulting compound of the formula I in which G represents an ammonium cation, turn by treatment with acid Bronsted into the corresponding compound of formula I in which G represents hydrogen.

2. The method according to claim 1, wherein the compound of formula IV, IVa or IVb is used in equimolar amount or preferably in excess of 5 to 50 mol.% in terms of the compound of formula II.

3. The method according to claim 1, wherein the reaction is carried out at a temperature of from 0 to 200°C.

4. The method according to claim 1, wherein the solvent used toluene or one of the isomers of xylene, such as ortho-, meta - and para-xylene.

5. The method according to claim 1, in which the condensation is carried out in an atmosphere of inert gas.

6. The method according to claim 1, in which the reaction of the compound of formula II with the compound of the formula IVa or IVb is carried out in the presence of a base.

7. The method according to claim 6, in which as the Foundation of the use of tertiary amine or pyridine.

8. The method according to claim 7, in which the base is used in a catalytic amount or in a molar excess, amounting to up to 5 in terms of the compound of formula II.

9. The compound of formula II

in which R1, R2, R3, Rsub> 6and R7have specified in claim 1 values.



 

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