WO1998027068A1

WO1998027068A1 - Method for producing 3-amino-1-phenyl-uracil derivatives by making 3,4-dihydro-2h-1,3-oxyazine-2,4 dion derivatives to react with hydrazine (adducts)

Info

Publication number: WO1998027068A1
Application number: PCT/EP1997/006823
Authority: WO
Inventors: Heinz-Jürgen Wroblowsky
Original assignee: Bayer Aktiengesellschaft
Priority date: 1996-12-17
Filing date: 1997-12-05
Publication date: 1998-06-25
Also published as: IL130088A0; BR9714514A; JP2001506248A; AU5754698A; EP0946521A1; DE19652432A1

Abstract

The invention relates to a novel method for producing 3-amino-1-phenyl-uracil derivatives of formula (I), wherein R?1, R2, R3, R4 and R5¿ have the meanings cited in the description, and in which substituted phenyloxazine-diones of formula (II) are made to react with hydrazine hydrate of formula (III): H¿2?N-NH2 . H2O or with acid adducts of hydrazine, optionally in the presence of an acid acceptor and optionally in the presence of a diluent.

Description

PROCESS FOR THE PREPARATION OF 3-AMINO-l-phenyl-uracil derivatives by imple _¬ HEATING of 3,4-dihydro-2H-l, 3-OXYAZIN-2,4-dione derivatives with hydrazine (adducts)

The present invention relates to a new process for the preparation of known 3-amino-1-phenyl-uracil derivatives.

It has already become known that certain 3-amino-1-phenyl-uracils can be prepared by reacting aminoalkenic acid esters with substituted phenyl isocyanates or with substituted phenyl-urethanes in the presence of bases and the resulting 1-phenyluracils with l- Brings aminooxy-2,4-dinitro-benzene to the reaction (cf. EP-A 0 408 382, EP-A 0 648 749 and WO 95-32 952). However, a disadvantage of these processes is that the desired substances are obtained in a relatively low yield and not always in sufficient purity. In addition, the required starting materials are not very suitable for syntheses on an industrial scale.

Furthermore, it is already known that certain phenyl uracils by reaction of

Aminoalkenoic acid-phenylamides can be prepared with carbonic acid derivatives (cf. WO 95-32 952). These substances can also be converted into the corresponding 3-amino-1-phenyl-uracils by amination. What is disadvantageous about this method, however, is that many stages have to be run through and the synthesis is therefore quite complex.

Finally, it is already known that certain 1,3-oxazin-2,4 (3H) -diones, which are unsubstituted on the nitrogen atom, react with hydrazine to uracilene, which carry an amino group as a substituent. In the corresponding reaction of 1,3-oxazin-2,4 (3H) -dions which are substituted on the nitrogen atom, however, no uracils are formed, but only pyrazole derivatives (cf. J. Heterocycl. Chem. 15 (1978),

1475-1478).

It has now been found that 3-amino-1-phenyluracil derivatives of the formula

in which

Rl represents hydrogen, cyano, nitro or halogen,

R ^{2 represents} cyano, nitro, halogen or optionally substituted alkyl or alkoxy,

R ^ for hydrogen, hydroxy, mercapto, amino, hydroxyamino, halogen, or for one of the radicals -R ⁷ , -QR ⁷ , -NH-R ⁷ , -NH-OR ⁷ , -NH-SO ₂ -R ⁷ , - N (SO ₂ -R ⁷ ) 2, -CQi-R ⁷ , -CQ ¹ -Q ² -R ⁷ , -CO NH-R ⁷ , -Q ² -CQ R ⁷ , -NH-CQ R ⁷ , -N (SO ₂ -R ⁷ ) (CQ ¹ -R ⁷ ), -Q ² -CQ ¹ -Q ² -R ⁷ , -NH-CQ QR ⁷ or -Q ² -CQ ¹ -NH-R ⁷ ,

wherein

represents O, S, SO or SO ₂ ,

Ql and Q ² independently of one another represent oxygen or sulfur and

R ⁷ represents optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl,

R4 represents hydrogen, halogen or optionally substituted alkyl, and

R5 represents alkyl substituted by fluorine and / or chlorine obtained when substituted phenyloxazin-diones of the formula

in which

Rl, R ² , R ^, R ^ and R ^ have the meanings given above,

with hydrazine hydrate of the formula

H ₂ N-NH ₂ • H ₂ O (III)

or with acid adducts of hydrazine

optionally in the presence of an acid acceptor and optionally in the presence of a diluent at temperatures between -50 ° C and + 100 ° C.

It is extremely surprising that 3-amino-1-phenyl-uracil derivatives of the formula (I) can be prepared by the process according to the invention, since, based on the prior art, it was assumed that pyrazole Derivatives arise. Contrary to expectations, this is not the case. Rather, 3-amino-1-phenyl-uracil derivatives are obtained in a smooth reaction.

The method according to the invention is characterized by a number of advantages. So the required starting materials are easily accessible and also in larger quantities. Furthermore, the implementation of the reaction and the isolation of the desired substances pose no problems. It is particularly favorable that the 3-amino 1-phenyl-uracil derivatives are accessible in a one-step reaction from the substituted phenyloxazine dions of the formula (II). Otherwise, the method is widely applicable.

If 3- (4-cyano-2,5-difluorophenyl) -3,4-dihydro-6-trifluoromethyl-2H-1,3-oxazin-2,4-dione and hydrazine hydrate are used as starting materials, the course can be changed of the method according to the invention are outlined by the following formula:

Formula (II) provides a general definition of the phenyloxazin-diones required as starting materials when carrying out the process according to the invention. Compounds of the formula (II) in which

R ^{1 represents} hydrogen, cyano, nitro, fluorine, chlorine or bromine,

R ^{2 represents} cyano, nitro, fluorine, chlorine, bromine or in each case optionally substituted by fluorine and / or chlorine alkyl or alkoxy having 1 to 4 carbon atoms,

R ^ for hydrogen, hydroxy, mercapto, amino, hydroxyamino, halogen, or for one of the radicals -R ⁷ , -QR ⁷ , -NH-R ⁷ , -NH-OR ⁷ , -NH-SO ₂ -R ⁷ ,

-N (SO ₂ -R ⁷ ) ₂ , -CQ R ⁷ , -CQ QR ⁷ , -CQ NH-R ⁷ , -Q ² -CQ ¹ -R ⁷ , -NH-CQ R ⁷ , -N (SO ₂ -R ⁷ ) (CQ ¹ -R ⁷ ), -Q ² -CQ Q ² -R ⁷ , -NH-CQ Q ² -R ⁷ or -Q ² -CQ ¹ -NH-R ⁷ ,

woπn

represents O, S, SO or SO ₂ , Ql and Q ² independently of one another represent oxygen or sulfur and

R ⁷ for optionally by cyano, halogen, C 1 -C 4 alkoxy, C 1 -C 4 alkyl thio, C 4 -C 4 alkyl carbonyl, C 1 -C 4 alkoxy carbonyl or C1-C4-

Alkylamino-carbonyl-substituted alkyl having 1 to 6 carbon atoms,

or represents in each case optionally substituted by cyano, carboxy, halogen, C 4 -C 4 alkylcarbonyl, C 1 -C 4 alkoxycarbonyl or C 4 -C 4 alkylaminocarbonyl alkenyl or alkynyl each having 2 to 6 carbon atoms,

or for cycloalkyl or cycloalkylalkyl, each of which is optionally substituted by cyano, carboxy, halogen, C 1 -C 4 -alkylcarbonyl or C 1 -C 4 -alkoxycarbonyl, each having 3 to 6 carbon atoms in the cycloalkyl group and optionally 1 to 4 carbon atoms in the alkyl part stands,

or for each case optionally up to three times by hydroxy,

Mercapto, amino, cyano, carboxy, carbamoyl, thiocarbamoyl, C \ - C4- alkyl, Cι-C4-haloalkyl, Cι -C4-alkoxy, C \ -C4-haloalkoxy, Ci _L -C4-alkylthio, Cι-C4 -Halogenalkylthio, -C -C-alkylsul- finyl, -C-C4-alkylsulfonyl, -C-C4-alkylamino and / or dimethylamino-substituted aryl or arylalkyl each having 6 or 10 carbon atoms in the aryl group and optionally 1 to 4 carbon atoms in the alkyl part ,

or for each, optionally up to three times, by hydroxy, mercapto, amino, cyano, carboxy, carbamoyl, thiocarbamoyl, C \ -

C4- alkyl, -C-C4-haloalkyl, Cι-C4-alkoxy, C -C4-haloalkoxy, C \ -C -alkylthio, C -C4-haloalkylthio, C 1 -C4- alkylsul- finyl, C 1 -C 4 alkylsulfonyl, C 4 -C 4 alkylamino and / or dimethylamino substituted heterocyclyl or heterocyclylalkyl having 2 to 6 carbon atoms and 1 to 3 nitrogen atoms and / or 1 or 2 oxygen atoms and / or a sulfur atom in the heterocyclyl group and optionally 1 to 4 carbon atoms in the alkyl part,

R ^ represents hydrogen, fluorine, chlorine, bromine or alkyl having 1 to 6 carbon atoms which is optionally substituted by fluorine and / or chlorine and

R5 represents fluorine and / or chlorine-substituted alkyl having 1 to 6 carbon atoms.

Substituted phenyloxazin-diones of the formula (II) in which

Rl represents hydrogen, fluorine or chlorine,

R ^{2 represents} cyano, fluorine, chlorine, bromine, methyl or trifluoromethyl,

R ^ for hydroxy, mercapto, amino, fluorine, chlorine, bromine or for one of the residues

-R ⁷ , -QR ⁷ , -NH-R ⁷ , -NH-OR ⁷ , -NH-SO ₂ -R ⁷ , -N (SO ₂ -R ⁷ ) ₂ , -CQ -R ⁷ , -CQ Q ² -R ⁷ , -CQ NH-R ⁷ , -Q ² -CQ! -R ⁷ , -NH-CQ R ⁷ ,

-N (SO -R ⁷ ) (CQ ¹ -R ⁷ ), -Q ² -CQ ¹ -Q ² -R ⁷ , -NH-CQ Q ² -R ⁷ or -Q ² -CQ ¹ -NH-R ⁷ stands,

wherein

Q represents O, S, SO or SO ₂ ,

Ql and Q ² independently of one another represent oxygen or sulfur and for each methyl, ethyl, n- or i-propyl, n-, i-, s- or substituted by cyano, fluorine, chlorine, methoxy, ethoxy, methylthio, ethylthio, acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, methylaminocarbonyl or ethylaminocarbonyl t-butyl is,

or for in each case optionally substituted by cyano, carboxy, fluorine, chlorine, bromine, acetyl, propionyl, n- or i-butyroyl, methoxycarbonyl, ethoxycarbonyl, n- or i-propoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, n- or i-propylaminocarbonyl penyl, butenyl, propynyl or butynyl,

or represents cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl or cyclohexylmethyl, each optionally substituted by cyano, carboxy, fluorine, chlorine, bromine, acetyl, propionyl, methoxycarbonyl or ethoxycarbonyl,

or for each optionally single to triple by hydroxy, mercapto, amino, cyano, carboxy, carbamoyl, thiocarbamoyl, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, methylthio, ethylthio, difluoromethylthio, trifluoromethyl Methylsulfinyl, ethylsulfinyl, methylsulfonyl, methylamino, ethylamino and / or dimethylamino substituted phenyl, benzyl or phenylethyl,

or for in each case optionally once or twice by hydroxy, mercapto, amino, cyano, carboxy, carbamoyl, thiocarbamoyl, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, difluoromethyl, di- chloromethyl, trifluoromethyl, trichloromethyl, chlorodifluoromethyl, fluorodichloromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, methylthio, ethylthio, difluoromethylthio, trifluoromethylthio, methylsulfinyl, ethylsulfinyl, methylsulfonyl, ethyl amino, ethylamino and / or dimethylamino substituted heterocyclyl or heterocyclylalkyl from the series oxiranyl, oxetanyl, furyl, tetrahydrofuran, dioxolanyl, thienyl, tetrahydrothienyl, pyrrolyl, pyrazolyl, imidazolyl, triazolyl, oxazolyloliazolylyliazolyloloxylyliazolyloloxylyliazolylyloxylyliazolyloloxylyliazolyloloxylylazolyloloxylylazolyloloxylylazolyloloxylylazolyloloxylylazolyloloxylylazolyloloxylylazolyloloxazolyloloxylylazolyloxazylylazolyloxazylyloxazolyloxazylyloxazolyl-oxazolylazol-oxazolyl-oxazolyl-oxazolyl-oxazolyl-oxazolyl-oxazol-oxazol-oxazol-oxazol-oxazol-oxazol-ox-z--azazil-ox-z--az-ox- Pyridinyl, pyrimidinyl, triazinyl, pyrazolylmethyl, furylmethyl, thienylmethyl, oxazolylmethyl, isoxazolylmethyl, thiazolylmethyl, pyridinylmethyl, pyrimidinylmethyl,

R ^{4 represents} hydrogen, fluorine, chlorine, bromine, methyl, ethyl or trifluoromethyl and

R5 stands for trifluoromethyl, chlorodifluoromethyl, fluorodichloromethyl or pentafluoroethyl.

The substituted phenyloxazin-diones of the formula (II) have hitherto been known in some cases

(see EP-A 0 371 240 and EP-A 0 638 563).

The substituted phenyloxazinediones of the formula are new

in which

A ^{1 represents} fluorine or chlorine,

A ^{2 represents} cyano,

A ^{3 represents} fluorine or chlorine, A ^{4 represents} hydrogen, fluorine, chlorine or methyl and

A ^ stands for trifluoromethyl, chlorodifluoromethyl, fluorodichloromethyl or pentafluoroethyl.

The substituted phenyloxazin-diones of the formula (Ila) can be prepared by

a) substituted ß-keto-carboxanilides of the formula

in which

A *, A ² , A ³ , A ⁴ and A ^ have the meanings given above,

with carbonic acid derivatives of the formula

in which

l \ and Z ^{2 are} identical or different and represent halogen, alkoxy, aryloxy, imidazolyl or triazolyl,

optionally in the presence of an acid binder, such as sodium hydride, pyridine or 4-dimethylaminopyridine, and optionally in the presence of a Diluent, such as toluene or tetrahydrofran, at temperatures between -20 ° C and + 150 ° C (see the manufacturing examples)

The remaining substituted phenyloxazin-diones of the formula (II) can be prepared in the same way by substituting substituted β-keto-carboxylic acid anilides of the formula

in which

R *, R ² , R ³ , R ⁴ and R ^ have the meanings given above,

implemented by the process (a) with carbonic acid derivatives of the formula (V).

Formula (V) provides a general definition of the carbonic acid derivatives required as reaction components in process (a). In this formula, Z * and Z ^{2 are the} same or different and are preferably chlorine, methoxy, ethoxy, phenoxy, imidazol-1-yl or 1,2,4-triazol-l-yl.

The carbonic acid derivatives of the formula (V) are known.

The substituted β-keto-carboxylic acid anilides are generally defined by the formula (IV). In this formula, R, R ² , R ³ , R ⁴ and R ^ preferably have those meanings which have already been mentioned as preferred for these radicals in connection with the description of the substituted phenyloxazin-diones of the formula (II). The substituted β-keto-carboxanilides of the formula (IV) have hitherto been known in some cases (cf. J. Heterocycl. Chem. 2, 113 to 119 (19659; Synthesis 1992, 1213 to 1214 and DE-A 4 218 159).

The substituted ß-keto-carboxanilides of the formula are new

in which

Al represents fluorine or chlorine,

A ^{2 represents} cyano,

A ^{6 represents} fluorine, chlorine, methylsulfonylamino or ethylsulfonylamino,

A ^{4 represents} hydrogen, fluorine, chlorine or methyl and

The substituted β-keto-carboxylic acid anilides of the formula (IVb) can be prepared by

(b) b-keto esters of the formula

in which

A ⁴ and A-> have the meanings given above and

R represents alkyl having 1 to 4 carbon atoms,

with substituted anilines of the formula

in which

Al, A ² and A ^ have the meanings given above,

optionally in the presence of a diluent, e.g. N, N-dimethyl-formamide or N-methyl-pyrrolidone at temperatures between 50 ° C and 150 ° C, or if one

(c) substituted aminoalkenoic anilides of the formula

in which

Al, A ² , A ³ , A ⁴ and A ^{6 have} the meanings given above,

with water, optionally in the presence of an acidic catalyst such as hydrochloric acid, sulfuric acid or methanesulfonic acid, and optionally in present in the presence of an organic solvent, such as, for example, methanol, ethanol, n- or i-propanol, n-, i-, s- or t-butanol, at temperatures between 0 ° C. and 100 ° C. (cf. the preparation examples).

The other β-keto-carboxylic acid anilides of the formula (IV) can be prepared in the same way.

Formula (VI) provides a general definition of the β-keto esters required as starting materials when carrying out process (b). In this formula, A ⁴ and A ^ have the meanings given above. R preferably represents methyl or ethyl.

The hydrazine hydrate of the formula (III) required as a reaction component when carrying out the process according to the invention or its acid adducts are known.

Hydrazine hydrate or its addition salt with hydrochloric acid is preferably usable.

Suitable acid acceptors for carrying out the process according to the invention are all customary inorganic or organic bases. Alkali metal or alkaline earth metal acetates, amides, carbonates, hydrogen bicarbonates, hydrides, hydroxides or alkanolates, such as sodium, potassium or calcium acetate, lithium, sodium or potassium, are preferably used - or calcium amide, sodium, potassium or calcium carbonate, sodium, potassium or calcium hydrogen carbonate, lithium, sodium, potassium or calcium hydride, lithium, sodium,

Potassium or calcium hydroxide, sodium or potassium methoxide, ethanolate, n- or -i-propanolate, -n-, -i-, -s- or -t-butanolate; also basic organic nitrogen compounds, such as, for example, trimethylamine, triethylamine, tripropylamine, tributylamine, ethyldiisopropylamine, N, N-dimethylcyclohexylamine, dicyclohexylamine, ethyldicyclohexylamine, N, N-dimethylaniline, N, N- Dimethylbenzylamine,

Pyridine, 2-methyl, 3-methyl, 4-methyl, 2,4-dimethyl, 2,6-dimethyl, 3,4-dimethyl and 3,5-dimethyl-pyridine, 5- Ethyl-2-methyl-pyridine, 4-dimethylamino-pyridine, N-methyl-piperidine, 1,4-diazabicyclo [2,2,2] octane (DABCO), 1,5-diazabicyclo- [4,3,0 ] -non-5-ene (DBN), or 1.8 diazabicyclo [5,4,0] -undec-7-ene (DBU). Suitable diluents for carrying out the process according to the invention are all customary inert, organic solvents and also water. Aliphatic, alicyclic or aromatic, optionally halogenated hydrocarbons, such as, for example, gasoline, benzene, toluene, xylene,

Chlorobenzene, dichlorobenzene, petroleum ether, hexane, cyclohexane, dichloromethane, chloroform, carbon tetrachloride; Ethers such as diethyl ether, diisopropyl ether, dioxane, tetrahydrofuran or ethylene glycol dimethyl or diethyl ether; Ketones, such as acetone, butanone or methyl isobutyl ketone; Nitriles such as acetonitrile, propionitrile or butyronitrile; Amides such as N, N-dimethylformamide, N, N-dimethylacetamide, N-methylformanilide, N-methylpyrrolidone or hexamethylphosphoric triamide; Esters such as methyl acetate or ethyl acetate, sulfoxides such as dimethyl sulfoxide, alcohols such as methanol, ethanol, n- or i-propanol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, their mixtures with water or pure water.

The reaction temperatures can be varied within a substantial range when carrying out the process according to the invention. In general, temperatures between -50 ° C and + 100 ° C, preferably between -30 ° C and + 80 ° C.

The process according to the invention is generally carried out under atmospheric pressure. However, it is also possible to work under increased pressure or, if no volatile components are used, under reduced pressure.

To carry out the process according to the invention, 1 to 5 mol, preferably 1.0 to 2.5 mol, of hydrazine hydrate of the formula (III) or its acid adduct is generally employed per mol of substituted phenyloxazinedione of the formula (II).

In a preferred embodiment of the process according to the invention, the substituted phenyloxazinedione of the formula (II) is placed in a suitable diluent and the hydrazine hydrate of the formula (III) is slowly metered in. The reaction mixture is then stirred - if appropriate at elevated temperature - until the end of the reaction. Working up is carried out using customary methods (cf. the production examples). The 3-amino-1-phenyl-uracil derivatives of the formula (I) and their use as herbicides are already known (cf. EP-A 0 408 382, EP-A 0 648 749 and WO 95-32 952).

The process according to the invention is illustrated by the following examples.

MANUFACTURING EXAMPLES

example 1

A mixture of 15.9 g (0.05 mol) of 3- (4-cyano-2,5-difluorophenyl) -3,4-dihydro-6-trifluoromethyl-2H-1,3-oxazin-2,4-dione , 2.5 g (0.05 mol) of hydrazine hydrate and 100 ml of ethanol are stirred for 20 hours at room temperature and for a further hour under reflux. The product obtained in crystalline form after cooling is isolated by suction.

4.8 g (27% of theory) of 3-amino-1- (4-cyano-2,5-difluorophenyl) -3,6-di-hydro-2,6-dioxo-4-trifluoromethyl- 1 (2H) -pyrimidine, melting point 227 ° C.

Manufacture of raw materials

Example 2

120 g of a 20% solution of phosgene in toluene are stirred at 40 ° C. to a mixture of 60 g (0.20 mol) of N- (4-cyano-2,5-difluorophenyl) -3-oxo 4,4,4-trifluoro-1-butanoic acid amide, 40 ml of pyridine, 4 g of 4-dimethylamino-pyridine and 1.5 liters of toluene added dropwise. The reaction mixture is then stirred at 40 ° C. for a further 4 hours. Excess phosgene is then blown out with nitrogen. The remaining mixture is washed three times with water, dried over sodium sulfate and filtered. The solvent is carefully distilled off from the filtrate in a water jet vacuum.

63.7 g (77.5% of theory) of 3- (4-cyano-2,5-difluorophenyl) -3,4-dihydro-6-trifluoromethyl-2H-1,3-oxazin-2 are obtained. 4-dione as a viscous mass, which gradually crystallizes through.

Melting point (after recrystallization from isopropanol): 127 ° C.

Example 3

Procedure fb)

A mixture of 9.7 g of 4,4,4-trifluoroacetessιgsaureethylester (about 95% ιg), 7.8 g of 4-cyano-2,5-difluoro-aniline and 25 ml of N-methyl-pyrrolidone is 23 hours at 110 ° C. Stirred After the addition of a further 4.8 g of 4,4,4-trifluoroacetoacetic acid ethyl ester, the mixture is stirred for a further 7 hours at 110 ° C. After cooling, the crystalline product is isolated by suction

4.0 g (22% of theory) of N- (4-cyano-2,5-difluorophenyl) -3-oxo-4,4,4-trifluoro-1-butanoic acid amide with a melting point of 189 ° C. are obtained

Procedure (c)

A mixture of 29.1 g (0.10 mol) of N- (4-cyano-2,5-difluorophenyl) -3-amino-4,4,4-trifluoro-2-butenoic acid amide, 150 ml of water, 19 , 2 g of methanesulfonic acid and 450 ml of n-butanol is stirred for 20 hours at room temperature (approx. 20 ° C.). Then the organic phase is separated off, washed twice with 150 ml of water each time, dried over sodium sulfate and filtered The solvent is carefully distilled off in a water jet vacuum. The residue is stirred with 200 ml of cyclohexane and the crystalline product is isolated by suction

27.2 g (92% of theory) of N- (4-cyano-2,5-difluorophenyl) -3-oxo-4,4,4-tπfluoro-1-butanoic acid amide with a melting point of 189 ° C. are obtained

A mixture of 1.58 g (5 mmol) of N- (4-cyano-2,5-difluorophenyl) -3-amino-4,4,4-tπfluoro-2-butenoic acid amide, 5 ml of water, 5 ml of IN - Hydrochloric acid and 15 ml n-butanol is stirred for 20 hours at room temperature (approx. 20 ° C). Then 10 ml water are added. The organic phase is separated, washed twice with water, dried over sodium sulfate and filtered. The solvent is removed from the filtrate in water - jet vacuum carefully distilled off. The residue is stirred with 5 ml of cyclohexane and the crystalline product is isolated by suction.

1.4 g (90% of theory) of N- (4-cyano-2,5-difluorophenyl) -3-oxo-4,4,4-trifluoro-1-butanoic acid amide with a melting point of 189 ° C. are obtained.

Claims

claims

1. Process for the preparation of 3-amino-1-phenyl-uracil derivatives of the formula

in which

Rl represents hydrogen, cyano, nitro or halogen,

R ³ for hydrogen, hydroxy, mercapto, amino, hydroxyamino, halogen, or for one of the radicals -R ⁷ , -QR ⁷ , -NH-R ⁷ , -NH-OR ⁷ , -NH-SO ₂ -R ⁷ , - N (SO ₂ -R ⁷ ) ₂ , -CQ R ⁷ , -CQ ^l -Q ² -R ⁷ , -CQ NH-R ⁷ , -Q ² -CQ ¹ -R ⁷ , -NH-CQ R ⁷ , - N (SO ₂ -R ⁷ ) (CQ ¹ -R ⁷ ),

-Q ² -CQ ¹ -Q ² -R ⁷ , -NH-CQ QR ⁷ or -Q ² -CQ! -NH-R ⁷ ,

wherein

Q represents O, S, SO or SO ₂ ,

Ql and Q ² independently of one another represent oxygen or sulfur and R ⁷ represents optionally substituted alkyl, alkenyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl,

R ^{4 represents} hydrogen, halogen or optionally substituted alkyl and

R5 represents alkyl substituted by fluorine and / or chlorine,

characterized in that substituted phenyloxazin-diones of the formula

in which

Rl, R ² , R ³ , R ⁴ and R5 have the meanings given above,

with hydrazine hydrate of the formula

H ₂ N-NH • H ₂ O (III)

or with acid adducts of hydrazine

2. The method according to claim 1, characterized in that substituted phenyloxazin-diones of the formula (II) are used as starting materials, in which rather Rl represents hydrogen, cyano, nitro, fluorine, chlorine or bromine,

R ² for cyano, nitro, fluorine, chlorine, bromine or in each case optionally substituted by fluorine and / or chlorine alkyl or alkoxy with 1 to

4 carbon atoms,

R ³ for hydrogen, hydroxy, mercapto, amino, hydroxyamino, halogen, or for one of the radicals -R ⁷ , -QR ⁷ , -NH-R ⁷ , -NH-OR ⁷ , -NH-SO ₂ -R ⁷ , - N (SO ₂ -R ⁷ ) ₂ , -CQ R ⁷ , -CQ Q ² -R ⁷ , -CQ NH-R ⁷ ,

-Q ² -CQ ¹ -R ⁷ , -NH-CQi-R ⁷ , -N (SO ₂ -R ⁷ ) (CQ ¹ -R ⁷ ),

-Q ² -CQ ¹ -Q ² -R ⁷ , -NH-CQi-Q ² ^ ⁷ or -C CQ ^Ϊ -NH-R ⁷ ,

wherein

Q represents O, S, SO or SO ₂ ,

Ql and Q ² independently of one another represent oxygen or sulfur and

R ⁷ for optionally substituted by cyano, halogen, C1-C4-alkoxy, C \ - C4-alkylthio, -C-C4 ~ alkyl-carbonyl, -C-C4-alkoxy-carbonyl or Cι-C4-alkylamino-carbonyl alkyl with 1 to 6 carbon atoms,

or represents in each case optionally cyano-, carboxyl-, halogen, C _j -C 4 alkyl-carbonyl, Cι-C4-alkoxy-carbonyl or Cγ- C4-alkylamino-carbonyl-substituted alkenyl or alkinyl each having 2 to 6 carbon atoms,

or for each optionally by cyano, carboxy, halogen, C _] -C4-alkyl-carbonyl or -C-C4-alkoxy-carbonyl sub- substituted cycloalkyl or cycloalkylalkyl, each having 3 to 6 carbon atoms in the cycloalkyl group and optionally 1 to 4 carbon atoms in the alkyl part,

or for up to three times each, if necessary

Hydroxy, mercapto, amino, cyano, carboxy, carbamoyl, thiocarbamoyl, C1-C4-alkyl, Cj-C4-haloalkyl, C1-C4-alkoxy, C] -C4-haloalkoxy, Cι-C4-alkylthio, Cτ-C4-halo - Aralkylthio, -C-C4-alkylsulfinyl, C \ -C4-alkylsulfonyl, -C-C4-alkylamino and / or dimethylamino substituted aryl or arylalkyl, each having 6 or 10 carbon atoms in the aryl group and optionally 1 to 4 carbon atoms in the alkyl part,

or for up to three times each, if necessary

Hydroxy, mercapto, amino, cyano, carboxy, carbamoyl, thiocarbamoyl, C1-C4-alkyl, C \ -C4-haloalkyl, C1-C4- alkoxy, C] -C4-haloalkoxy, Cι -C4-alkylthio, Cι-C4- Haloalkylthio, -C-C4-alkylsulfinyl, C j -C4-alkylsulfonyl, -C-C4-alkylamino and / or dimethylamino substituted

Heterocyclyl or heterocyclylalkyl having 2 to 6 carbon atoms and 1 to 3 nitrogen atoms and / or 1 or 2 oxygen atoms and / or a sulfur atom in the heterocyclyl group and optionally 1 to 4 carbon atoms in the alkyl part,

R ^{4 represents} hydrogen, fluorine, chlorine, bromine or alkyl which has 1 to 6 carbon atoms and is optionally substituted by fluorine and / or chlorine and

R ^{5 represents} fluorine and / or chlorine-substituted alkyl having 1 to 6 carbon atoms.

3. The method according to claim 1, characterized in that substituted phenyloxazine-diones of the formula (II) are used as starting materials, in which

Rl represents hydrogen, fluorine or chlorine,

R ³ for hydroxy, mercapto, amino, fluorine, chlorine, bromine or for one of the

Residues -R ⁷ , -QR ⁷ , -NH-R ⁷ , -NH-OR ⁷ , -NH-SO ₂ -R ⁷ , -N (SO ₂ -R ⁷ ) ₂ ,

-CQ R ⁷ , -CQ Q ² -R ⁷ , -CQ NH-R ⁷ , -Q ² -CQ ¹ -R ⁷ , -NH-CQ R ⁷ ,

-N (SO ₂ -R ⁷ ) (CQ ¹ -R ⁷ ), -Q CQ QAR ⁷ , -NH-CQ QR ⁷ or -Q ² -CQ ¹ -NH-R ⁷ ,

wherein

Q represents O, S, SO or SO ₂ ,

Ql and Q ² independently of one another represent oxygen or sulfur and

R ⁷ for methyl, ethyl, n- or i-propyl, n-, i-, each optionally substituted by cyano, fluorine, chlorine, methoxy, ethoxy, methylthio, ethylthio, acetyl, propionyl, methoxycarbonyl, ethoxycarbonyl, methylaminocarbonyl or ethylaminocarbonyl , s- or t-butyl,

or for each optionally by cyano, carboxy, fluorine, chlorine, bromine, acetyl, propionyl, n- or i-butyroyl, methoxycarbonyl, ethoxycarbonyl, n- or i-propoxycarbonyl, methylaminocarbonyl, ethylaminocarbonyl, n- or i-propylaminocar- bonyl substituted propenyl, butenyl, propynyl or butynyl,

or for each optionally by cyano, carboxy, fluorine, 5 chlorine, bromine, acetyl, propionyl, methoxycarbonyl or

Ethoxycarbonyl substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl or cyclohexylmethyl,

10 or for each, if necessary, up to three times

Hydroxy, mercapto, amino, cyano, carboxy, carbamoyl, thiocarbamoyl, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, methylthio, ethylthio, difluoromethylthio, trifluoromethylthio, methylsulfinyl,

15 is ethylsulfinyl, methylsulfonyl, methylamino, ethylamino and / or dimethylamino substituted phenyl, benzyl or phenylethyl,

or for each optionally single or double by 20 hydroxy, mercapto, amino, cyano, carboxy, carbamoyl,

Thiocarbamoyl, methyl, ethyl, n- or i-propyl, n-, i-, s- or t-butyl, difluoromethyl, dichloromethyl, trifluoromethyl, trichloromethyl, chlorodifluoromethyl, fluorodichloromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, methylthio Ethyl 25 thio, difluoromethylthio, trifluoromethylthio, methylsulfinyl,

Ethylsulfinyl, methylsulfonyl, methylamino, ethylamino and / or dimethylamino substituted heterocyclic or heterocyclylalkyl from the series oxiranyl, oxetanyl, furyl, tetrahydrylolol, oxolylolazole, pyrolyzole

Thiazolyl, isothiazolyl, oxadiazolyl, thiadiazolyl, pyridinyl, pyrimidinyl, triazinyl, pyrazolylmethyl, furylmethyl, thienyl methyl, oxazolylmethyl, isoxazolylmethyl, thiazolylmethyl, pyridinylmethyl, pyrimidinylmethyl,