DE19741411A1 - Preparation of 3-aryl-uracil derivative useful as herbicide - Google Patents

Abstract

Preparation of 3-aryluracil derivatives of formula (I) comprises (a) reducing a nitrobenzene derivative of formula (VII) in presence of a rhodium, ruthenium, platinum, iridium or palladium catalyst which is modified by an organic or inorganic phosphorus compound with P in an oxidation state of <5, to give an aniline derivative of formula (VI); (b) reacting (VI) with phosgene or diphosgene to give an isocyanate of formula (V); and (c) reacting (V) with an enamine of formula (IV) in presence of dimethyl formamide, dimethyl sulphoxide, acetonitrile, propionitrile, ethyl acetate, tetrahydrofuran, dioxan, N-methylpyrrolidone, methyl-tert. butyl ether, dimethyl acetamide and/or toluene as solvent, in presence of 0.2-0.4 equivalents of a base selected from alkali(ne earth) metal hydrides and alkali metal alcoholates at -5 to +40 deg C, to give (I). R = (YQ)m(CO)nXR2; R1 = 1-4C alkyl, 3-4C alkenyl or 3-4C alkynyl; R2 = 3-6C alkenyl, 3-6C alkynyl, 3-8C cycloalkenyl, 6-8C bicycloalkenyl or 3-6C haloalkenyl; R3 = H, halo, 1-3C alkyl, 1-3C alkoxy, 1-3C haloalkyl, 1-3C haloalkoxy, CN or OH; or R3+R = N(R17)CO(CH2)pX3; R4 = H, F or Cl; Y = O, S, NR6 or COX1; X = O, S or NR7; X1 = O, S or NR8; R5-R8 = 1-4C alkyl, 1-4C haloalkyl, 3-6C alkenyl or 3-6C alkynyl; m, n, p = 0 or 1, provided that if n = 0 then m = 0; Q = 1-10C alkylene, the carbon atoms of which may complete a 1,1- or 1,2-linked 3-8C cycloalkylene ring; X3 = O or S; R17 = 3-6C alkenyl or 3-6C alkynyl; R16 = 1-6C alkyl.

Description

The present invention relates to a new process for the preparation of 3-phenyluracils.

3-Phenyluracile can e.g. B. by forming the uracil ring from open chain Aniline derivatives that already have the desired substitution pattern getting produced. So z. B. from US-A-5,183,492, 3-phenyluracile Formula VIII

in which among other things
R₁₀ C₁-C₄-alkyl, C₃-C₄-alkenyl or C₃-C₄-alkynyl
R₁₁ C₁-C₄ alkyl or C₁-C₄ haloalkyl;
R₁₃ is hydrogen, halogen, C₁-C₃-alkyl, C₁-C₃-alkoxy, C₁-C₃-haloalkyl, C₁-C₃-haloalkoxy, cyano or hydroxy;
R₁₂ is hydrogen, fluorine or chlorine; and
R₁₄ (C₃-C₆-alkenyloxy) carbonyl-C₁-C₄-alkyl mean, to be prepared in such a way that

A) in the case of compounds of the formula VIII in which R₁₁ is C₁-C₄-alkyl, a compound of formula IX

wherein R₁₂, R₁₃ and R₁₄ have the meaning given under formula VIII, with a compound of formula X

wherein R₁₁ C₁-C₄-alkyl and R₁₅ C₁-C₄-alkyl means, in the compound of formula XI

wherein R₁₁ is C₁-C₄-alkyl and R₁₂, R₁₃, R₁₄ and R₁₅ have the meaning given above, converted, subjecting them to cyclization under basic conditions and then alkylating the 1-position of the 3-phenyluracil obtained, or
B) in the case of compounds of the formula VIII in which R₁₁ is C₁-C₄-haloalkyl, a compound of the formula XII

wherein R₁₁ and R₁₅ have the meanings given above, with a Compound of formula XIII

wherein R₁₂, R₁₃ and R₁₄ have the meanings given above, or one Compound of formula XIIIa

wherein R₁₂ and R₁₃ have the meanings given above, in the compound of the formula XI

wherein R₁₁ is C₁-C₄-haloalkyl and R₁₂, R₁₃, R₁₄ and R₁₅ are the above have given meaning, converted this to a cyclization under  subject to basic conditions and then the 1-position of the 3-Phenyluracils obtained alkylated.

In WO 95/32952 it was described that 3-phenyluracile can be prepared by using the starting compound instead of one Aminocarbonylaminophenyl derivatives of the formula IX or Isocyanatophenyl derivative of the formula XIII or Alkyloxycarbonylaminophenyl derivatives of formula XIIIa one by reduction an aniline compound obtained from a corresponding nitrophenyl derivative, these with a β-keto ester or a β-ketocarboxylic acid halide in one Acetoacetanilide which converts with an ammonium salt into an enamine is transferred from which, after cyclization and alkylation, the below Compound of formula A listed.

According to WO 95/32952, compounds of the formula A

wherein
R represents the group - (YQ) _m - [C (O)] _n -X-R₂;
R₁ C₁-C₄ alkyl, C₃-C₄ alkenyl or C₃-C₄ alkynyl;
R₂ C₃-C₆ alkenyl, C₃-C₆ alkynyl, C₃-C₈ cycloalkenyl, C₆-C₈ bicycloalkenyl or C₃-C₆ haloalkenyl;
R₃ is hydrogen, halogen, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, C₁-C₃ haloalkoxy, cyano or hydroxy; or
R₃ and R together form the group -N (R₁₇) -C (O) - (CH₂) _n1 -X₃-;
R₄ is hydrogen, fluorine or chlorine;
R₅ C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₃-C₆ alkenyl or C₃-C₆ alkynyl;
Y is oxygen, sulfur, N-R₆ or C (O) -X₁;
X is oxygen, sulfur or N-R₇;
X₁ is oxygen, sulfur or N-R₈;
R₆, R₇ and R₈ independently of one another are C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₃-C₆-alkenyl or C₃-C₆-alkynyl;
m 0 or 1;
n 0 or 1;
Q is a C₁-C₁₀ alkylene group whose carbon atoms can form a 1,1- or 1,2-linked C₃-C₈ cycloalkyl ring;
n₁ 0 or 1;
X₃ is oxygen or sulfur; and
R₁₇ is C₃-C₆-alkenyl or C₃-C₆-alkynyl, with the proviso that m is 0 when n is 0,
made by
a) a compound of formula B.

wherein
R, R₃ and R₄ have the meaning given under formula A, in the presence of a catalyst containing platinum modified by lead, mercury, bismuth, germanium, cadmium, arsenic, antimony, silver or gold, to a compound of formula C.

wherein R, R₃ and R₄ have the meaning given under formula A, reduced,
b) this with a compound of formula D.

wherein R₅ has the meaning given under formula A and R₉ for chlorine or C₁-C₄ alkoxy is in an aprotic solvent to a compound of Formula E.

wherein R, R₃, R₄ and R₅ have the meaning given under formula A,
c) this in the presence of an enaminating agent such. B. ammonia, in the compound of formula F.

wherein R, R₃, R₄ and R₅ have the meaning given under formula A,
d) this in the presence of a base and an inert solvent with a compound of formula G.

wherein L₁ and L₂ independently of one another for halogen, C₁-C₄ alkoxy, imidazol-1-yl or 1,2,4-triazol-1-yl are ₁ to the compound of formula H.

wherein R, R₃, R₄ and R₅ have the meaning given under formula A, implemented and
e) this compound in an inert solvent in the presence of a base with a compound of formula K.

R₁-L₃ (K),

wherein L₃ is halogen or OSO₂OR₁ and R₁ is the formula A given Has meaning converted into the compound of formula A.

The present invention relates to a method for producing 3-phenyluracilene by reduction of a nitrophenyl derivative to the corresponding aniline compound, reaction of this aniline compound with Phosgene to the corresponding isocyanate, from which after reaction with an N-substituted enamine directly receives the compound of formula I which is characterized in that in the reduction of a nitrophenyl derivative the corresponding aniline compound is a very special, new catalyst is used and the implementation of the isocyanate with the enamine under special reaction conditions takes place.

According to the invention, it is therefore proposed in a method of manufacture of compounds of formula I.

wherein
R represents the group - (YQ) _m - [C (O)] _n -X-R₂;
R₁ C₁-C₄ alkyl, C₃-C₄ alkenyl or C₃-C₄ alkynyl;
R₂ C₃-C₆ alkenyl, C₃-C₆ alkynyl, C₃-C₈ cycloalkenyl, C₆-C₈ bicycloalkenyl or C₃-C₆ haloalkenyl;
R₃ is hydrogen, halogen, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, C₁-C₃ haloalkoxy, cyano or hydroxy; or
R₃ and R together form the group -N (R₁₇) -C (O) - (CH₂) _n1 -X₃-;
R₄ is hydrogen, fluorine or chlorine;
R₅ C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₃-C₆ alkenyl or C₃-C₆ alkynyl;
Y is oxygen, sulfur, N-R₆ or C (O) -X₁;
X is oxygen, sulfur or N-R₇;
X₁ is oxygen, sulfur or N-R₈;
R₆, R₇ and R₈ independently of one another are C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₃-C₆ alkenyl or C₃-C₆ alkynyl;
m 0 or 1;
n 0 or 1;
Q is a C₁-C₁₀ alkylene group whose carbon atoms can form a 1,1- or 1,2-linked C₃-C₈ cycloalkyl ring;
n₁ 0 or 1;
X₃ is oxygen or sulfur; and
R₁₇ C₃-C₆-alkenyl or C₃-C₆-alkynyl, with the proviso that m is 0 when n is 0 by reduction
a) a compound of formula VII

wherein R, R₃ and R₄ have the meaning given under formula I, in Presence of a catalyst to a compound of formula VI

wherein R, R₃ and R₄ have the meaning given under formula I,
b) reaction of this compound with phosgene or diphosgene to form the isocyanate of the formula V.

wherein R, R₃ and R₄ have the meaning given under formula I,
c) reaction of this compound with an enamine of formula IV

wherein R₁ and R₅ have the meaning given under formula I and R₁₆ C₁-C₆-alkyl for the compound of formula I, in process step a) as catalyst, rhodium, Ruthenium, platinum, iridium or palladium catalysts, which with an inorganic or organic phosphorus compound of the oxidation state less than 5 are modified use and process step c) in pure dimethylformamide, dimethyl sulfoxide, Acetonitrile, propionitrile, ethyl acetate, tetrahydrofuran, dioxane, N-methylpyrrolidone, methyl  tert-butyl ether, dimethylacetamide or toluene, or mixtures thereof as solvents and in the presence of 0.2 to 0.4 equivalents of a base selected from the group of Alkali and alkaline earth metal hydrides and the group of alkali metal alcoholates in one Temperature from -5 ° C to + 40 ° C.

It is known that aromatic nitro compounds in the presence of noble metal sators and hydrogen can be reduced to aromatic amines in good yields can. In the presence of other hydrogenatable groups, such as Examples are carbon multiple bonds, nitrile, imino or carbonyl groups special measures are required to prevent the formation of unwanted by-products prevent that otherwise often only with great effort or in particularly unfavorable cases cannot be separated from the desired product. It is particularly difficult selective reduction when there are several hydrogenatable groups in a compound.

The prior art contains a number of proposals for the selective reduction of nitroaromatics substituted with hydrogenatable groups. For example, in WO 95/32941 and in WO 95/32952 (see above) a process for the hydrogenation of Nitroaromatics, which by at least one group with a Carbon multiple bond are described. As catalysts with Lead, mercury, bismuth, germanium, cadmium, arsenic, antimony, silver or gold modified precious metal catalysts proposed. These catalysts are true basically suitable and can also be used on an industrial scale, anyway Such catalysts cannot always with regard to their activity and selectivity satisfy.

In US-A-4 020 107 phosphorous acid, hypophosphorous acid or their Derivatives as an additive in the hydrogenation of nitro substituted on aromatic compounds with halogen aromatics with Pt or Pd / activated carbon and hydrogen proposed.

These systems are true of the halogen substituents present in the molecule selective, but often have limited reactivity. It is therefore used in many Cases of considerable amounts of arylhydroxylamine were observed (Catalysis of Organic Reactions, Vol 18, (1988), 135-147); idem, Catalysis in Organic Synthesis, 1980, 107-117).  

Catalytic hydrogenation of aromatic nitro compounds to the corresponding aromatic amines run through several intermediate intermediates. From The relevant nitroso compounds and in particular the Hydroxylamine intermediate. This is, for example, by M. Freifelder in the Handbook of Practical Catalytic Hydrogenation, published by Wiley-Interscience, New York, 1971.

In practice, this hydroxylamine intermediate poses a particular problem because it under certain conditions in the reaction solution in large amounts can accumulate. This applies in particular to aromatic nitro compounds whose Hydrogenation gives relatively stable arylhydroxylamines. This is particularly critical if the Hydrogenation in a slurry batch reactor is carried out on an industrial scale. In extreme cases, several tons of arylhydroxylamine can be formed in this way.

The accumulation of arylhydroxylamines is undesirable in many ways. For one thing known that such compounds are often thermally unstable and when heated with or can disproportionate without H₂ with strong heat emission. Through the released heat can trigger further decomposition reactions, which then in can lead to events with severe explosions. W.R. Tong et al, AICHE Loss Prev. 1977, (11), 71-75 describe such an event in the reduction from 3,4-dichloronitrobenzene to 3,4-dichloroaniline.

This instability makes an in-depth and complex thermal examination of Hydrogen mixtures are essential before the start of production. In particular, that thermal behavior of the possible hydroxylamine intermediates thoroughly examined will. F. Stoessel, J. Loss Prev. Process Ind., 1993, Vol. 6, No. 2, 79-85 describes this Procedure using the example of the hydrogenation of nitrobenzene to aniline.

Arylhydroxylamines are also known to be strong carcinogens and therefore contribute interrupted or incomplete hydrogenation represents a great risk potential (J.A. Miller, Cancer Res. 3 (1970), 559).

A third problem area is the production of a pure amine. Are during the Hydrogenation or at the end of the reaction significant amounts of arylhydroxylamine present, this can lead to condensation, whereby undesirable and colored  Form azo or azoxy products. Since the amount of arylhydroxylamine varies from batch to batch product quality changes in purity and aspect.

The above problems are exacerbated by the fact that occurring concentrations or even the maximum possible concentrations of these Hydroxylamine intermediate not even in known and well-studied processes can be predicted. The presence of contaminants in the trace area can the spontaneous accumulation of hydroxylamine intermediates in unpredictable Trigger way. For example, J. R. Kosak, in Catalysis of Organic Reactions, describes Vol 18, (1988), 135 that the simple addition of 1% NaNO₃ the accumulation in the Hydrogenation of 3,4-dichloronitrobenzene increased from originally <5% to about 30%.

Contrary to expectations, the process step a) used catalyst systems that select nitro aromatics to the corresponding Amino compounds can be reduced without the unsaturated carbon, -CN or -CO bonds of the substituents on the nitroaromatic are hydrogenated simultaneously.

Surprisingly, only a small number occur in process step a) Concentrations of the unwanted hydroxylamine. However, in those cases where Larger amounts of hydroxylamine must be expected by adding this catalytic amounts of a co-catalyst, such as a vanadium compound, be suppressed practically completely. Hydroxylamine is usually observed Concentrations below 1%. This has made it possible to get higher concessions trations of nitroaromatics, which makes it extremely economical Process management contributes.

The activity and selectivity of the catalyst systems is high, especially at very high sensitive compounds such as nitrobenzoic acid propargylester.

Since no further heavy metal connections are necessary for the modification, it can there is also no contamination of the end products with heavy metals.

The catalyst systems can easily be obtained from known and in some cases commercially available ones Standard Pt or Pd catalysts are made so that a constant catalyst quality is guaranteed, which is important for large-scale production.  

As a rule, a low pressure (approx. 5 bar) and a relatively low temperature (approx. 100 ° C) can be used.

Another advantage of the method over known reduction methods such as An example of B'champ or sulfide reduction is that in process step a) no Fe- Sludge and no acidic or sulphurous waste water to be disposed of have to. The compound of formula VI is obtained in high purity since there are practically no azo or azoxy compounds are formed and the reaction can be carried out in conventional reactors without using special materials. The hydrogenation, the final phase in particular is rapid. This has considerable advantages in terms of quality consistency and economy.

The method has a high level of operational reliability, since in method step a) Hydroxylamine formation, if necessary by adding a co-catalyst, is practical can be suppressed.

In the context of the present invention, alkyl is, for example, methyl, ethyl, Isopropyl, n-propyl, n-butyl, iso-butyl, sec-butyl and tert-butyl.

Haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chlorine methyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, 2,2,2-trichloroethyl and pentafluoroethyl; preferably trichloromethyl, Difluorochloromethyl, trifluoromethyl and dichlorofluoromethyl.

Alkenyl is to be understood as straight-chain or branched alkenyl, such as. B. Allyl, methallyl, 1-methylvinyl, but-2-en-1-yl, pentenyl or 2-hexenyl.

The alkynyl groups occurring in the definitions of the substituents can straight-chain or branched, such as, for example, propargyl, 3-butynyl, 1-methylpropargyl, 1-pentynyl or 2-hexynyl.

Alkoxy is, for example, methoxy, ethoxy, propoxy and i-propoxy.  

The above definitions include halogen, fluorine, chlorine, bromine and iodine preferably to understand fluorine, chlorine and bromine.

Cycloalkenyl stands for example for cyclobutenyl, cyclopentenyl, 3-methylcyclopentenyl and cyclohexenyl.

Q as a C₁-C₁₀ alkylene group means, for example, -CH₂-, -CH₂-CH₂-, -CH₂-CH₂- CH₂-, -CH₂-CH₂-CH₂-CH₂, -CH₂-CH₂-CH₂-CH₂-CH₂, -CH₂-CH₂-CH₂-CH₂-CH₂-CH₂, -CH₂-CH (CH₃) -CH₂-CH₂-CH₂-CH₂, -CH (CH₃) -, -C (CH₃) ₂-, -CH (CH₃) -CH₂-, -CH₂- CH (CH₃) -, -C (CH₂CH₃) ₂-, -C (CH₂CH₂CH₃) ₂- or -C (CH₂CH₂CH₂CH₃) ₂-.

Q as a C₁-C₁₀ alkylene group, the carbon atoms of which are 1,1- or 1,2- form linked C₃-C₈ cycloalkyl ring means, for example

In those cases where R and R₃ together form the group -N (R₁₇) -C (O) - (CH₂) _n1 - X₃-, this group is linked in such a way that -N (R₁ an) - to the 3-position of R and -X₃- to the 4-position of R₃ on the phenyl ring.

The presence of at least one asymmetric carbon atom in the compounds of formula I, e.g. B. wherein R is the group - (YQ) _m - [C (O)] _n -X-R₂, and Q is a branched C₁-C₁₀ alkylene group, for example - CH (CH₃) - or -CH (CH₃) - CH₂-, or / and R₂ represents a branched C₃-C₆-alkenyl or C₃-C₆-alkynyl group, has the consequence that the compounds can occur both in optically active individual isomers and in the form of racemic mixtures. The optically active compounds of formula I can by known separation processes, such as. B. fractional crystallization can be obtained from the racemic mixtures. In the present invention, the active compounds of the formula I are understood to mean both the pure optical antipodes and the racemates or diastereomers. Unless the individual optical antipodes are specifically referred to, the given formula is to be understood as meaning those racemic mixtures which result from the stated production process.

Those with the method according to the invention are preferred Compounds of formula I prepared in which R₅ is C₁-C₄ haloalkyl; in particular wherein R₅ is difluoromethyl, trifluoromethyl, difluorochloromethyl, Trichloromethyl or pentafluoroethyl.

In particular, those compounds of the formula I are also prepared using the process according to the invention in which R and R₃ together form the group -N (R₁₇-C (O) - (CH₂) _n1 -X₃-; n₁ 0; and X₃ is sulfur.

Those compounds of the formula I in which R and R₃ together form the group -N (R₁₇) -C (O) - (CH₂) _n1 -X₃- are also preferably prepared using the process according to the invention; n₁ 1; and X₃ means oxygen.

Particularly preferred is the process for the preparation of compounds of formula I, wherein R and R₃ together form the group -N (R₁₇) -C (O) - (CH₂) _n1 -X₃-; R₁₇ means allyl, methallyl, propargyl or 1-methylpropargyl.

Also to be emphasized is the process for the preparation of compounds of the formula I in which R and R₃ together form the group -N (R₁₇) -C (O) - (CH₂) _n1 -X₃-; R₁ methyl; R₄ is hydrogen or fluorine; and R₅ is C₁-C₄ haloalkyl; in particular wherein R₅ is trifluoromethyl, trichloromethyl, difluorochloromethyl, difluoromethyl or pentafluoroethyl.

In addition, the preparation of those compounds of the formula I is advantageous where R₄ is hydrogen or fluorine.

The method according to the invention is particularly suitable for the production of Compounds of formula I, wherein R₃ is halogen.  

Also to be emphasized is the preparation of compounds of the formula I in which R₁ represents C₁-C₄-alkyl.

The preparation of compounds of the formula I is very particularly preferred wherein R₁ is methyl, R₃ is chlorine, R₄ is hydrogen or fluorine, and R₅ is trifluoromethyl means, preferably m and n being 1.

It is also advantageous to prepare those compounds of the formula I in which Q for

stands; especially where Q for

stands.

The preparation of compounds of the formula I in which Y represent C (O) X₁, n represents 1 and X₁ and X represent oxygen or wherein X-R₂C₃-C₆-alkenyloxy means.

The process according to the invention is particularly suitable for the production of
2-cyano-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) pyr-imidinyl) 1-methylallyl benzoate;
<S <2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) pyrimidinyl) benzoic acid 1-methylallyl ester;
2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) -pyrimidinyl) -4-fluorobenzallylamide;
2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) pyr-imidinyl) thiobenzoic acid allyl amide;
2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) -pyrimidinyl) - benzoic acid- (1-allylaminocarbonyl-1-methyl) -ethyl ester;
<S <2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) -pyrimidinyl) -benzoic acid- (1-allylaminocarbonyl-1-methyl) -methyl ester;
2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) -pyr-imidinyl) - benzoic acid- (1-allyloxy carbonyl-1-methyl) - ethyl ester;
2-Chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trichloromethyl-1 (2H) pyrimidinyl) - benzoic acid- (1-allyloxycarbonyl-1-methyl) ethyl ester ;
2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) -pyr-imidinyl) -4-fluorobenzoic acid- (1-allyloxycarbonyl-1-methyl) -ethyl ester; and
<S <2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) -pyrimidinyl) -benzoic acid- (1-methylallyloxycarbonyl-1-methyl) ethyl ester.

Platinum or palladium is preferably used as the noble metal catalyst, particularly preferably platinum.

The noble metal catalyst is preferred in an amount of 0.1 to 10% by weight, particularly preferably in an amount of 0.5 to 2% by weight, based on the aromatic used Nitro compound used.

Preference is given to using a noble metal catalyst containing 1 to 10% by weight of platinum contains. The platinum which can be used for the modification can be in the form of platinum black, platinum oxide or preferably applied in a metallic or oxidized form on a support will. Activated carbon and silicon dioxide in the form of pebbles are particularly suitable carriers acid or silica gel, aluminum oxide, calcium carbonate, calcium phosphate, calcium sulfate, Barium sulfate, titanium oxide, magnesium oxide, iron oxide, lead oxide, lead sulfate or lead carbonate, Activated carbon, aluminum oxide or silicon dioxide are particularly preferred. On top Platinum applied carrier material is commercially available or can be after the Methods familiar to those skilled in the art, as disclosed, for example, in DE-OS-20 42 368 are manufactured.

In principle, all inorganic or organic phosphorus compounds can be used as modifiers applications in which the phosphorus has an oxidation state of less than 5 having. Examples of phosphorous acid derivatives are described in US Pat. No. 4,020,107 called.  

Particularly suitable phosphorus compounds are phosphines P (R _a ) _3-p (H) _p , phosphinous acid HO-P (H) _q (R _a ) _2-q , phosphites P (OR _a ) ₃, phosphine oxides O = P (R _a ) _3-p (H) _p ,
Hypophosphonic acids

Hypophosphorous acids
O = P (OH) (H) _q (R _a ) _2-q and phosphorous acids O = P (OH) ₂H or O = P (OH) ₂R _a , where R _{a is} linear or branched C₁-C₁₂ alkyl, C₆ -C₁₆ aryl or C₄-C₁₆ heteroaryl and q is 0, 1 or 2 and p is 0, 1, 2 or 3.

Examples of R _a equal to C₁-C₁₂-alkyl are methyl, ethyl, the different isomers of propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl and dodecyl. C₆-C₁₆ aryl can be unsubstituted or substituted phenyl, naphthyl, anthracyl, tetralin, indene, azuline or biphenyl.

C₄-C₁₆ heteroaryl are, for example, unsubstituted or substituted quinoline, Isoquinoline, pyridine, pyrimidine, pyrazine, indole, thiazole, pyrazole, oxazole, imidazole or Fluorenone.

R _a is preferably C₁-C₆-alkyl or phenyl which is unsubstituted or substituted by C₁-C₆-alkyl or C₁-C Phen-alkoxy.

The phosphorus compounds, if they are acids, can be used as free acids, Salts, esters or amides are present.

Diphenylphosphine, triphenylphosphine, phosphinous acid, their salts, Amides and esters, diphenylphosphinic acid, diphenylphosphite, diethylphosphite, Phosphine oxides, phosphorous acid, its salts or esters, hypophosphorous acid, their salts, amides and esters.

Phosphorous acid, its salts, amides and esters as well as Hypophosphorous acid and its salts, amides and esters.  

Preferred salts are those with cations from the group of alkali, Alkaline earth metals or the ammonium cation.

Preferred alkali and alkaline earth metals are Li, Na, K, Ca or Mg.

The ammonium cation can be NH₄⁺, (C₁-C₆-alkyl) ₄N⁺ or mixed with H and C₁-C₆-alkyl substituted ammonium cation.

Examples of C₁-C₆-alkyl are methyl, ethyl, the various isomers of propyl, butyl, Pentyl or hexyl.

The modification of the noble metal catalysts can in principle during or afterwards to the manufacturing process of the hydrogenation catalyst. However, it is preferred before the catalyst is added to the reaction mixture, or it is carried out directly in the Reaction mixture by either dissolving or dispersing the phosphorus compound added separately and both stirred together with the solution to be hydrogenated. It is also possible during the modification the pH of the catalyst mixture by adding of acids or bases to a certain value. It is also possible to modify the noble metal catalyst with the phosphorus compound by one mixes both as solids or the phosphorus compound in one Solvent dissolves and slurries the precious metal catalyst with the solution and then filtered. The modified catalyst can be stored and if necessary the hydrating solution can be added.

The noble metal catalyst is preferably modified with the phosphorus compound before catalytic hydrogenation.

The phosphorus compound can be soluble or in the reaction medium to be hydrogenated be dispersed.

The ratio of the noble metal catalyst to the modifying phosphorus compound is preferably 1 to 0.1 to 1 to 1000, particularly preferably 1 to 5 to 1 to 200 Ge important parts.  

A preferred procedure is obtained if one additionally uses a catalytic Amount of a co-catalyst is added. The addition of the co-catalyst can in many cases in which an accumulation of arylhydroxylamine is expected to be effective prevent.

Purely inorganic or optionally organic come as co-catalysts Ligands of complex-bound ions from transition metals in question. The Co-catalysts can either be dissolved in the reaction medium, on a support material be applied to the catalyst or the modified catalyst.

Preferred ions of transition metals are Fe ²⁺ , Fe ³⁺ , Ru ³⁺ , Mn ²⁺ , Mn ³⁺ , Co ²⁺ , Co ³⁺ or vanadium compounds in which the vanadium has the oxidation state 0, II, III, IV or V. .

Elemental vanadium or vanadium compounds in which are particularly preferred the vanadium has the oxidation state 0, II, III, IV or V.

The co-catalysts can be dissolved in catalytic amounts or in the reaction medium be dispersed.

Another also preferred procedure is obtained when the vanadium compound is mixed with the precious metal catalyst or applied to it. Of the Precious metal catalyst can already be modified with the phosphorus compound or can only be modified afterwards. The vanadium compound can also in principle Course of the manufacturing process of the hydrogenation catalyst, before or after the modes fication with a phosphorus compound, applied to this.

It is also preferred if the vanadium compound is initially suitable Carrier material is applied and is dispersed in this form in the reaction medium. Suitable carrier materials are, for example, all commercially available for the production Powdery hydrogenation catalysts used support materials as above are mentioned. Activated carbon is particularly suitable.  

The application to the catalyst or the support material takes place in a simple manner Example by dissolving the vanadium compounds, slurrying the catalyst or of the carrier material in the solution and subsequent filtration.

If necessary, the pH of the is added during the application of the vanadium compound Slurry to the desired value by adding acids or bases set.

If the vanadium compounds are not soluble in the reaction medium, they can also in dispersed, slurried form with the slurried catalyst mixed and filtered together.

Elementary comes as vanadium compounds of the oxidation state 0, II, III, IV or V. Vanadium and purely inorganic compounds in question, but also organic Complexes with, for example, oxalate or acetylacetonate are possible.

Preferred are vanadium compounds such as V₂O₅, V₂O₄, vanadium (III) acetylacetonate, vanadium (IV) oxyacetylacetonate or those which are a purely inorganic salt, oxo salt or the hydrate of a purely inorganic salt or oxo salt. Examples are VOCl₃, VCl₆⁻, [VO (SCN) ₄] ^2- , VOSO₄, NH₄VO₃, VCl₃, VOCl, VCl₂ or the corresponding halides with F or Br. The compounds are in aqueous solution depending on the pH value in various forms of hydrate ( FA Cotton, G. Wilkinson, Inorganic Chemistry, Verlag Chemie Weinheim 1968, 2nd edition page 757-766).

The vanadates or the hydrates of vanadates from the oxidation are particularly preferred stage V and vanadium (III) acetylacetonate, vanadium (IV) oxyacetylacetonate and whole Vanadium (III) acetylacetonate, vanadium (IV) oxyacetylacetonate are particularly preferred.

In the vanadates, the ammonium, Li, Na or K vanadates or hydrate are these Vanadate preferred.  

The vanadium compound is preferred in an amount of 1-2000 ppm, especially preferably in an amount of 5-1000 ppm based on the aromatic to be hydrogenated Nitro compound used.

The weight ratio of vanadium compound to noble metal kata is preferably Analyzer 1 to 1 to 1 to 10000, particularly preferably 1 to 10 to 1 to 1000 and whole particularly preferably 1 in 50 to 1 in 750.

Process step a) is carried out at a pressure of 1 to 100 bar, preferably at a Pressure of 1 to 40 bar and particularly preferably at a pressure of 1 to 5 bar carried out.

The temperature can be from + 0 ° to + 160 ° C, preferably it is +200 to + 140 ° C and particularly preferably 200 to 100 ° C.

If the compound to be hydrogenated is liquid at the reaction temperature, the Hydrogenation can be carried out without solvent or if the resulting Amino compound is liquid under the reaction conditions, this can be used as a solvent to serve.

However, it is also possible to add solvents. The uncritical choice of the Solvent is a particular advantage of process step a) des inventive method. Solvents with high Solving power can be used in the presence of unmodified Platinum catalysts are not sufficiently inert, such as ketones. Preferred solvents are water, alcohols such as methanol, ethanol, n-propanol, i-propanol n-butanol, the isomeric butanols and cyclohexanol, ether, Esters and ketones such as diethyl ether, methyl tert-butyl ether, Tetrahydrofuran, dioxane, dimethoxyethane, ethyl acetate, Butyl acetate, butyrolactone, acetone, methyl ethyl ketone, methyl i-Bu tylketone or cyclohexanone, carboxylic acids such as acetic acid and propionic acid, dipolar aprotic solvents such as dimethylformamide, N-methylpyrrolidone, Dimethylacetamide, sulfolane, dimethyl sulfoxide or acetonitrile, apolar Solvents such as toluene or xylene, chlorinated aromatic hydrocarbons such as methylene chloride, C₃-C₇ alkanes or cyclohexane.  

These solvents can be used in pure form or as mixtures. In particularly preferred embodiments of the method according to the invention as a solvent tetrahydrofuran, toluene, xylene in pure form or as a mixture with the solvents mentioned above, in particular with alcohols and / or C₁-C₄- Carboxylic acids used.

If solvents are used, the concentration of nitroaromatic is in the Solution preferably 5 to 50% by weight, particularly preferably 10 to 30% by weight.

The reaction in process step a) is preferably carried out in the liquid phase carried out, in particular with a powdered catalyst either continuously or discontinuously as bottom phase hydrogenation or in the bubble column or with one formed catalyst in a trickle bed. Furthermore, the reaction in the gas phase with a powdered catalyst in a fluidized bed or with a shaped catalyst in a fixed bed be performed.

The method is also suitable when CC, -CN multiple bonds, carbonyl and Halogen groups simultaneously as substituents in the entire molecule or in the side chain occurrence.

Process step b) is essentially known per se. The reaction will preferably in the temperature range from + 20 ° C to + 140 ° C. As Solvents come aliphatic and aromatic hydrocarbons, halogenated hydrocarbons, ethers, and esters in question, such as. E.g. pentane, Hexane, heptane, octane; Benzene, toluene; Xylene, chloroform, carbon tetrachloride, Methylene chloride, chlorobenzene, dichlorobenzene, diethyl ether, t-butyl methyl ether, Tetrahydrofuran, dioxane, anisole, ethyl acetate or butyl acetate, preferably Toluene, tetrahydrofuran, dioxane or ethyl acetate.

The formation of the isocyanate is carried out by first 0.1 to 1.0 equivalents of phosgene or diphosgene, preferably phosgene, in the Introduces solvent and then at a temperature of 40 ° C to 100 ° C metered the aniline while at the same time another 1.0 to 2.0 equivalents Phosgene or diphosgene, preferably phosgene, are introduced. After Stopping the reaction will result in excess phosgene or diphosgene as well  Hydrochloric acid removed by heating the reaction mixture to reflux. The Isocyanate can be used as a solution or, if desired, after distilling off the Solvent are used in the following reaction step.

From WO 95/17391 is known compounds of the formulas A₁ and B₁

wherein Z₁ and Z₂ are oxygen or sulfur, at least one of the Groups represent sulfur; Rx for alkyl, Ry for hydrogen or alkyl, Alkenyl, alkynyl or alkylcarbonyl, Rs for hydrogen, halogen, cyano or for optionally substituted alkyl, Rt for hydrogen or halogen, Rv for Halogen, cyano, nitro, amino or an aminoalkylsulfonylalkyl group and Rz for Alkyl is to be prepared in such a manner by using an enamine of the formula C₁

with a cyanoaryl iso (thio) cyanate of the formula D₁

optionally in the presence of a reaction auxiliary and optionally in In the presence of a diluent.

The reactions specifically disclosed in the preparation examples are described in a dimethylformamide / toluene solvent mixture at temperatures of -70 ° C or -15 ° C, with 1 equivalent of sodium hydride as base is used. The yields of only 9 or 25% of Th. Are however completely, especially for large-scale applications insufficient.

It has now surprisingly been found that the yields of such Reactions can increase significantly if the implementation according to process step c) in pure dimethylformamide, dimethyl sulfoxide, acetonitrile, propionitrile, ethyl acetate, Tetrahydrofuran, dioxane, N-methylpyrrolidone, methyl tert-butyl ether, dimethylacetamide or Toluene, or mixtures thereof as solvents in the presence of 0.2 to 0.4 Equivalents of a base selected from the group of alkali and alkaline earth metal hydrides or the group of alkali metal alcoholates at a temperature of -5 ° C to + 40 ° C carries out.

Preferred bases in reaction step c) are potassium tert-butoxide, sodium tert-butylate, sodium methylate, sodium ethylate, potassium methylate, potassium ethylate, Sodium hydride, potassium hydride, sodium pentylate, potassium pentylate and 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), potassium is very particularly preferred tert-butylate and potassium tert-pentylate. The base is particularly preferred in one Amount from 0.25 to 0.35, in particular 0.3 equivalents with respect to the used enamine of formula IV used. A particularly preferred one Temperature range is 0 ° C to + 20 ° C, especially 0 ° C to + 5 ° C.

The reagents can be added in various ways. For example, the base can be in pure dimethylformamide, dimethyl sulfoxide, Acetonitrile, propionitrile, ethyl acetate, tetrahydrofuran, dioxane, N-methylpyrrolidone, Methyl tert-butyl ether, dimethylacetamide or toluene, or mixtures thereof submit, add the compound of formula IV and then the Enter compound of formula V, or the compound of formula IV and V as  Submit mixture and then base in pure dimethylformamide, Dimethyl sulfoxide, acetonitrile, propionitrile, ethyl acetate, tetrahydrofuran, dioxane, N-methylpyrrolidone, methyl tert-butyl ether, dimethylacetamide or toluene, or add their mixtures or the base in pure dimethylformamide, Dimethyl sulfoxide, acetonitrile, propionitrile, ethyl acetate, tetrahydrofuran, dioxane, N-methylpyrrolidone, methyl tert-butyl ether, dimethylacetamide or toluene, or submit their mixtures and then a mixture of the compound Add formula IV and V. In a preferred variant of the invention In step c) of the process, the base is placed in pure dimethylformamide, Dimethyl sulfoxide, acetonitrile, propionitrile, ethyl acetate, tetrahydrofuran, dioxane, N-methylpyrrolidone, methyl tert-butyl ether, dimethylacetamide or toluene, or their mixtures before and then gives the compound of formula IV and then the compound of formula V.

The enamines of formula IV can be prepared, for example, by to obtain a compound of formula II

with a compound of formula XXIII

H-N-R₁ (XXIII)

implements. Such reactions are described for example in JP 05140060-A.

The starting products of formula VII are either known or according to known methods can be produced.

For example, compounds of formula VII, wherein m and n are 1 and Y is C (O) -X₁, are prepared according to the following scheme:

T₁ and T₂ stand for reagents for the introduction of a leaving group L₄ or

L₅ (e.g. SOCl₂, COCl₂, (COCl) ₂, Ac₂O, (imidazol-1'-yl) ₂CO, Me₂N, or cyanuric acid chloride); and L₄ and L₅ independently of one another halogen (esp.Cl), O-CO-alkylC _1-4 or imidazol-1'-yl.

The individual reaction steps can e.g. B. can be carried out as follows:

XIV → XVa:

The carboxylic acid XIV is in an inert solvent (LM) at -20 to + 150 ° C. (preferably 0 to + 100 ° C) with a suitable reagent T₁ in the activated Acid derivative XVa transferred. The preferred acid derivative XV is chloride (L₄ = Cl).

XVa → XVIIa:

The compound of formula XVa is in the presence of a base (see below) in one inert solvents at -10 to + 150 ° C, preferably 0 to + 100 ° C with a Acid derivative XVI converted to XVIIa.

If X₁ is oxygen, the acid XIV can alternatively with the alcohol XVI by acid-catalyzed esterification in an inert solvent at -10 to + 150 ° C to be converted to XVIIa. As acid catalysts z. B. H₂SO₄, HCl, H₃PO₄, BF₃OEt₂ can be used. If necessary, can be made Water of reaction are continuously removed from the reaction mixture, e.g. B. by azeotropic distillation in a solvent such as toluene or xylene.

XVIIa → XVIIIa:

The compound of formula XVIIa thus obtained is used analogously to that for Compound of formula XIV described method using T₂ in an inert Solvents (such as toluene, xylene, ethyl acetate, dioxane, tetrahydrofuran or chloroform, ethylene chloride, 1,1,1-trichloroethane, dichloromethane, in one Temperature from -20 to + 150 ° C, preferably 0 to + 100 ° C, to XVIIIa um.

XVIIIa → VIIb:

By acylation with the compound of formula XVIIIa, HXR₂ (XIX) finally in an inert solvent and in the presence of a base at Temperature from -20 to + 150 ° C (preferably 0 ° to + 60 ° C) in the acid derivative Formula VIIb implemented. If desired, a catalyst such as 4-dimethylaminopyridine can be added. Instead of a solvent  also the organic base used, e.g. B. excess pyridine or quinoline can be used as a solvent.

Alternatively, the activated acid derivative XVa in the presence of a base in an inert organic solvent (LM) at a temperature of -20 to + 150 ° C, preferably 0 ° to + 60 ° C, optionally with the addition of a catalyst such as 4-dimethylaminopyridine, with an intermediate XX directly to VIIb be implemented.

Intermediates of formula XX are known in part from US-A-5,183,492 or can be produced using analog methods.

The intermediates of formula VII, in which R and R₃ together form the group -N (R₁₇-C (O) - (CH₂) _n1 -X₃-; n₁ 0; and X3 is sulfur (starting materials which belong to the 5-amino-2 (3H) -benzthiazolones of the formula VIc in Table 19) are known or can be prepared by known processes, for example as described in US Pat. No. 4,888,428.

The corresponding amines of the formula VIc are also known or can by known methods such. For example, described in US-A-4,888,428 will.

The intermediates of formula VII, wherein R and R₃ together form the group -N (R₁₇) -C (O) - (CH₂) _n1 -X₃-; n₁ 0; and X₃ is oxygen (starting materials which lead to the 5-amino-2 (3H) -benzoxazolones of the formula VIc in Table 19) are known or can be prepared by known processes such as, for. B. described in EP-A-0 415 642.

The corresponding amines of the formula VIc are also known or can by known methods such. B. described in EP-A-0 415 642 will.  

The intermediates of formula VII, wherein R and R₃ together form the group -N (R₁₇) -C (O) - (CH₂) _n1 -X₃-; n₁ 1; and X₃ is oxygen or sulfur (starting materials which lead to the 6-amino-3 (4H) -benzoxa- or -thiazines of the formula VId in Table 24) are known or can be prepared by known processes such as. Described in EP-A-0 170 191 or EP-A-0 349 876.

The corresponding amines of the formula VId are also known or can by known methods such. B. in EP-A-0 170 191 or EP-A-0 349 876 described, manufactured.

Bases

As bases come e.g. B. alkali and alkaline earth carbonates (NaHCO₃, K₂CO₃) or Alkaline earth oxides such as CaO, or tertiary amines such as trialkylamines (NEt₃), Pyridine bases such as pyridine, collidine or quinoline in question.

If desired, the reactions can be carried out under phase transfer catalytic Conditions.

The compounds of formula I prepared according to the invention can, for. B. as Active ingredient in herbicidal compositions for controlling weeds and grasses in Crop crops are used.

Manufacturing examples Example A1: Impregnation of activated carbon with ammonium vanadate

300 mg of ammonium vanadate with 600 ml of deionized water are placed in a stirred vessel in front. Then add 20 g of activated carbon and stir for 30 minutes. Then filter the impregnated activated carbon and washes it in portions with 600 ml deionized Water after. Finally, the vanadium-containing coal is dried in a vacuum Drying cabinet at 60 ° C to constant weight. 18.8 g of modified coal are obtained with a vanadium content of 13.6 mg / g.

Examples B: hydrogenations

Example B1: Preparation of 5-amino-2-chloro-benzoic acid-1-allyloxycarbonyl-1-methyl-ethyl ester

In a stirred autoclave, a solution of 16.1 g of 2- (2-chloro-5- nitrobenzoyloxy) -2-methyl-propionic acid allyl ester and 100 ml of toluene with 0.9 g of one after Example A1 produced with activated carbon containing vanadium. In a separate glass jar put 82 mg Pt-carbon catalyst with 50 mg hypophosphorous acid (50%) and 2 ml deionized water and stir for 10 minutes. The catalyst suspension is rinsed then with 4 ml of deionized water in the autoclave and hydrogenated for 2 hours a temperature of 100 ° C and a hydrogen pressure of 20 bar. After cooling and Inerting the stirred autoclave with nitrogen, the catalyst is filtered off and with 20 ml Washed toluene. After working up by distillation, 14 g of 5-amino-2-chlorine are obtained 1-allyloxycarbonyl-1-methyl-ethyl benzoate with a HPLC content of 98.9% (yield 94.8% of theory).  

1 H-NMR (CDCl₃, 250 MHz) 1.62 ppm (s, 6H); 3.65 ppm (s, 2H); 4.6 ppm (d, 2H); 5.2 ppm (q, 2 H); 5.85 ppm (m, 1H); 6.65 ppm (m, 1H); 7.0 ppm (m, 1H); 7.1 ppm (m, 1H).

In an analogous manner, those listed in Table 1 below can be used Compounds of formula VIa are prepared.

In the following Tables 1 to 10, Y₃ represents the group X₁-Q-C (O) -X-R₂ or -X-R₂, where X₁, Q, X and R₂ are as defined under formula I.  

Table 1

Compounds of formula VIa

Example H2: Preparation of 5-isocyanato-2-chloro-benzoic acid 1-allyloxycarbonyl-1-methyl-ethyl ester

At a temperature of 50 ° C, 20 g of phosgene are introduced into 400 g of toluene. A solution of 150 g of 5-amino-2-chloro-benzoic acid is then metered in 1-allyloxycarbonyl-1-methyl-ethyl ester and 200 g of toluene within one Hour and simultaneously introduces 80 g of phosgene. After the end of the Addition keeps the temperature at 50 ° C for one hour and then heats up Removal of excess phosgene and hydrochloric acid from the reaction mixture to reflux to a temperature of 115 to 120 ° C. The accruing toluene isocyanate solution can be concentrated as needed. The Solvent is under vacuum at a pressure of 20-200 mbar and one Temperature from 65 ° C to 90 ° C completely distilled off. 5-isocyanato is obtained. 2-chloro-benzoic acid 1-allyloxycarbonyl-1-methyl-ethyl ester as crude product in a yield of 98% of theory Th.  

Example H3: Preparation of 2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1- (2H) pyrimidinyl) -benzoic acid 1-allyloxycarbonyl-1-methyl ethyl ester

0.347 g is suspended in 30 g of anhydrous (water content <0.01%) dimethylformamide (Content: 97%, 0.003 mol) potassium tert-butylate and heated to a temperature of 40 ° C. Then, at a temperature of 40 to 45 ° C, 1.97 g (content: 99.5%, 0.01 mol) of 3-methylamino-4,4,4-trifluorobut-2-enoate and maintains this temperature for another 30 minutes, creating a red-brown solution. After cooling the Reaction mixture to a temperature of 0 ° C is metered in within 30 minutes 3.51 g (content: 97%, 0.0105 mol) 5-isocyanato-2-chloro-benzoic acid 1-allyloxycarbonyl-1- methyl ethyl ester with the temperature being kept between 0 and 5 ° C. The The resulting dark brown solution is still 30 minutes after removing the cooling bath stirred long and the pH of the now dark red solution with 2.7 g of 1 M HCl to pH 7 (the content of 2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1- (2H) pyrimidinyl) -benzoic acid 1-allyloxycarbonyl-1-methyl-ethyl ester in this solution is 11%, which corresponds to a yield of 89%). Then that will The solvent was distilled off on a rotary evaporator and the residue (5.6 g) in 12 g Isopropyl alcohol recrystallized (the inorganic salts are removed by hot filtration away). After drying in a vacuum drying cabinet (60 ° C / 12 h), 4.10 g are obtained (86.3% of theory) 2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1- (2H) pyrimidinyl) - 1-allyloxycarbonyl-1-methyl-ethyl benzoate with a content of 99%.  

Example H4: Preparation of 2-chloro-5- (3,8-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1- (2H) -pyrimidinyl) -benzoic acid 1-allyloxycarbonyl-1-methyl- ethyl ester

0.347 g is suspended in 20 g of anhydrous (water content <0.01%) dimethylformamide (Content: 97%, 0.003 mol) potassium tert-butylate and heated to a temperature of 40 ° C. Then, at a temperature of 40 to 45 ° C, 1.97 g (content: 99.5%, 0.01 mol) of 3-methylamino-4,4,4-trifluorobut-2-enoate and maintains this temperature for another 30 minutes, creating a red-brown solution. After cooling the Reaction mixture to a temperature of 0 ° C is metered in within 30 minutes 3.51 g (content: 97%, 0.0105 mol) 5-isocyanato-2-chloro-benzoic acid 1-allyloxycarbonyl-1- methyl ethyl ester with the temperature being kept between 0 and 5 ° C. The The resulting dark brown solution is still 30 minutes after removing the cooling bath stirred long and the pH of the now dark red solution with 2.7 g of 1 M HCl to pH 7 (the content of 2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1- (2H) pyrimidinyl) -benzoic acid 1-allyloxycarbonyl-1-methyl-ethyl ester in this solution is 13.1%, which corresponds to a yield of 79%). Then that will Solvent was distilled off on a rotary evaporator and the residue (5.4 g) in 12 g Isopropyl alcohol recrystallized (the inorganic salts are removed by hot filtration away). After drying in a vacuum drying cabinet (60 ° C / 12 h), 3.68 g are obtained (77.5% of theory) 2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1- (2H) pyrimidinyl) - 1-allyloxycarbonyl-1-methyl-ethyl benzoate with a content of 98.6%.  

Example H5: Preparation of 2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1- (2H) pyrimidinyl) -benzoic acid 1-allyloxycarbonyl-1-methyl-ethyl ester

In a mixture of 1.97 g (content: 99.5%, 0.01 mol) of 3-methylamino-4,4,4-trifluorobut-2- ethyl enate and 3.51 g (content: 97%, 0.0105 mol) of 5-isocyanato-2-chloro-benzoic acid 1-allyloxycarbonyl-1-methyl-ethyl ester is added at a temperature of 0 to 5 ° C Suspension of 20 g dry (water content <0.01%) dimethylformamide and 0.347 g (Content: 97%, 0.003 mol) potassium tert-butoxide in such a way that the temperature of the Reaction mixture does not exceed 5 ° C. The pH of the resulting dark red The solution is adjusted to pH 7 with 2.6 g of 1 M HCl (the content of 2-chloro-5- (3,6-dihydro-2,6- dioxo-3-methyl-4-trifluoromethyl-1- (2H) pyrimidinyl) benzoic acid 1-allyloxycarbonyl-1-methyl ethyl ester in this solution is 11.2%, which corresponds to a yield of 61.4%). The solvent is then distilled off on a rotary evaporator and the Crystallized residue (5.5 g) in 10 g isopropyl alcohol (the inorganic salts are removed by hot filtration). After drying in a vacuum drying cabinet (60 ° C / 12 h) 2.75 g (58.1% of theory) of 2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4- trifluoromethyl-1- (2H) pyrimidinyl) -benzoic acid 1-allyloxycarbonyl-1-methyl-ethyl ester with a grade of 98.2%.  

Example H6: Preparation of 2-chloro-5- (3.6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1- (2H) pyrimidinyl) -benzoic acid 1-allyloxycarbonyl-1-methyl-ethyl ester

To a suspension of 20 g dry (water content <0.01%) dimethylformamide and 0.347 g (content: 97%, 0.003 mol) of potassium tert-butylate is added to a mixture of 1.97 g (Content: 99.5%, 0.01 mol) of 3-methylamino-4,4,4-trifluorobut-2-enoic acid and 3.51 g (Content: 97%, 0.0105 mol) 5-isocyanato-2-chloro-benzoic acid 1-allyloxycarbonyl-1-methyl ethyl ester in such a way that the temperature does not exceed 30 ° C. The ph of the The resulting dark red solution is adjusted to pH 7 with 2.8 g of 1 M HCl (the content of 2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1- (2H) pyrimidinyl) benzoic acid 1- allyloxycarbonyl-1-methyl-ethyl ester in this solution is 10.8%, which is a yield of 59.2%). Then the solvent on a rotary evaporator distilled off and the residue (5.5 g) recrystallized in 10 g of isopropyl alcohol (the inorganic salts are removed by hot filtration). After drying in Vacuum drying cabinet (60 ° C / 12 h) gives 2.75 g (58.1% of theory) 2-chloro-5- (3.6- dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1- (2H) pyrimidinyl) benzoic acid 1- allyloxycarbonyl-1-methyl-ethyl ester with a content of 98.6%.

The following tables can be used in an analogous manner Compounds of the formula I are prepared:  

Table 2

Compounds of formula Ia

Table 3

Compounds of formula Ib

Table 4

Compounds of formula VIIa

Table 5

Compounds of formula XVII

Table 6

Compounds of formula XVIII

In the following tables 7 to 9, Y₀₃ means the group -Y-Q-C (O) -X-R₂ or -X-R₂, where Y is oxygen, sulfur or NR₆; and Q, X, R₂ and R₆ as are defined under formula I.

Table 7

Compounds of formula VIb

Table 8: Compounds of formula Ic

The uracil derivatives of the formula Ic mentioned in Table 8 required nitro compounds of the formula VIId

wherein R₂, R₃, R₄, X, Y, Q, m and n have the meaning given under formula I are known or can either by known methods
a) by alkylation of appropriately substituted nitrophenols (Y oxygen), nitrothiophenols (Y sulfur) or nitroanilines (YNR₆) of the formula VIIc

wherein R₃, R₄ and Y have the meaning given under formula I, with the Compound of formula XXI

L₄-Q _m - [C (O)] _n -X-R₂ (XXI),

wherein R₂, X, Q, m and n have the meaning given under formula I and L₄ is a leaving group, or appropriately substituted nitrobenzoyl derivatives of formula VIIe

wherein R₃, R₄ and X have the meaning given under formula I, with the Compound of formula XXII

R₂-L₄ (XXII),

wherein R₂ has the meaning given under formula I and L₄ represents a leaving group, z. in an inert solvent such as chlorinated alkanes. B. dichloromethane or chloroform, ketones z. B. acetone, nitriles e.g. B. acetonitrile, N, N-dimethylformamide, N-methylpyrrolidone or dimethyl sulfoxide can be obtained, the reaction temperatures being from -10 ° C to 150 ° C, preferably 0 ° to 100 ° C; as alkylating agents of formulas XXI and XXII z. B. corresponding halides or sulfonyloxy-substituted reagents such. B. tosylates or mesylates optionally with the addition of crown ethers or phase transfer catalysts, or
b) the alkylation can be analogous to Org. React. 42, 335 (1992), Editor DL Hughes, from the corresponding nitrophenols or thiophenols of the formula VIIc

wherein R₃ and R₄ have the meaning given under formula I and Y Is oxygen or sulfur, by reaction with an alcohol or thiol Formula XX

R₂-XH (XX),

wherein R₂ has the meaning given under formula I and X is oxygen or Is sulfur, in the presence of a trialkylphosphine such. B. tributylphosphine or Triphenylphosphine, and a suitable azodicarboxylic acid dialkyl ester such as e.g. B. diethyl azodicarboxylate or an azodicarboxylic acid diamide such. B. Azodicarboxylic acid dimorpholide in an inert solvent such as. B. Dioxane or tetrahydrofuran at temperatures from -20 ° to 140 ° C or through Esterification of the nitrobenzoyl derivatives of the formula VIIe

wherein R₃ and R₄ have the meaning given under formula I and X Is oxygen or sulfur, with an alcohol or thiol of formula XX

R₂-XH (XX),

wherein R₂ has the meaning given under formula I and X is oxygen or Sulfur is to be obtained.

The reactants and reagents can be equimolar or in excess (1 up to 5 equivalents) can be used.

Table 9

Compounds of formula VIIf

Table 10

Compounds of formula VIc

Table 11

Compounds of the formula Id

Table 12

Compounds of formula VId

Table 13

Compounds of formula Ie

Claims (50)

1. Process for the preparation of compounds of formula I. wherein
R represents the group - (YQ) _m - [C (O)] _n -X-R₂;
R₁ C₁-C₄ alkyl, C₃-C₄ alkenyl or C₃-C₄ alkynyl;
R₂ is C₃-C₆-alkenyl, C₃-C₆-alkynyl, C₃-C₈-cycloalkenyl, C₆-C₈-bicycloalkenyl or C₃- C₆-haloalkenyl;
R₃ is hydrogen, halogen, C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, C₁-C₃ haloalkoxy, cyano or hydroxy; or
R₃ and R together form the group -N (R₁₇) -C (O) - (CH₂) _n1 -X₃-;
R₄ is hydrogen, fluorine or chlorine;
R₅ C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₃-C₆ alkenyl or C₃-C₆ alkynyl;
Y is oxygen, sulfur, N-R₆ or C (O) -X₁;
X is oxygen, sulfur or N-R₇;
X₁ is oxygen, sulfur or N-R₈;
R₆, R₇ and R₈ independently of one another are C₁-C₄ alkyl, C₁-C₄ haloalkyl, C₃-C₆ alkenyl or C₃-C₆ alkynyl;
m 0 or 1;
n 0 or 1;
Q is a C₁-C₁₀ alkylene group whose carbon atoms can form a 1,1- or 1,2-linked C₃-C₈ cycloalkyl ring;
n₁ 0 or 1;
X₃ is oxygen or sulfur; and
R₁₇ is C₃-C₆-alkenyl or C₃-C₆-alkynyl, with the proviso that m is 0 when n is 0,
through reduction a) a compound of formula VII wherein R, R₃ and R₄ have the meaning given under formula I, in the presence of a catalyst to a compound of formula VI wherein R, R₃ and R₄ have the meaning given under formula I, b) reaction of this compound with phosgene or diphosgene to form the isocyanate of the formula wherein R, R₃ and R₄ have the meaning given under formula I, c) reaction of this compound with an enamine of formula IV wherein R₁ and R₅ have the meaning given under formula I and R₁₆ is C₁-C₆-alkyl to the compound of formula I, characterized in that in step a) as a catalyst rhodium, ruthenium, platinum, iridium or palladium catalysts, which with an inorganic or organic phosphorus compound of the oxidation state less than 5 are used, and process step c) in pure dimethylformamide, dimethyl sulfoxide, acetonitrile, propionitrile, ethyl acetate, tetrahydrofuran, dioxane, N-methylpyrrolidone, methyl tert-butyl ether, dimethylacetamide or toluene, or their mixtures as solvents and in the presence of 0.2 to 0.4 equivalents of base selected from the group of alkali and alkaline earth metal hydrides and the group of alkali metal alcoholates at a temperature of -5 ° C to + 40 ° C. 2. The method according to claim 1 for the preparation of compounds of formula I, wherein R₅ is C₁-C₄ haloalkyl. 3. The method according to claim 2 for the preparation of compounds of formula I, wherein R₅ for difluoromethyl, trifluoromethyl, difluorochloromethyl, trichloromethyl or Pentafluoroethyl is. 4. The method according to claim 1 for the preparation of compounds of formula I, wherein R and R₃ together form the group -N (R₁₇) -C (O) - (CH₂) _n1 -X₃-, n₁ 0 and X₃ is sulfur. 5. The method according to claim 1 for the preparation of compounds of formula I, wherein R and R₃ together form the group -N (R₁₇) -C (O) - (CH₂) _n1 -X₃-, n₁ 1 and X₃ is oxygen. 6. The method according to claim 1 for the preparation of compounds of formula I, wherein R and R₃ together form the group -N (R₁₇) -C (O) - (CH₂) _n1 -X₃- and R₁₇ allyl, methallyl, propargyl or 1- Methylpropargyl means. 7. The method according to claim 1 for the preparation of compounds of formula I, wherein R and R₃ together form the group -N (R₁₇) -C (O) - (CH₂) _n1 -X₃-, R₁ methyl, R₄ hydrogen or fluorine and R₅ Is C₁-C₄ haloalkyl. 8. The method according to claim 7, wherein R₅ trifluoromethyl, trichloromethyl, Is difluorochloromethyl, difluoromethyl or pentafluoroethyl.   9. The method according to claim 1 for the preparation of compounds of formula I, where R₄ is hydrogen or fluorine. 10. The method according to claim 1 for the preparation of compounds of formula I, wherein R₃ is halogen. 11. The method according to claim 1 for the preparation of compounds of formula I, wherein R₁ is C₁-C₄ alkyl. 12. The method according to claim 1 for the preparation of compounds of formula I, wherein R₁ is methyl, R₃ is chlorine, R₄ is hydrogen or fluorine, and R₅ is trifluoromethyl means. 13. The method according to claim 1 for the preparation of compounds of formula I, where m and n are 1. 14. The method according to claim 1 for the preparation of compounds of formula I, wherein Q is stands. 15. The method of claim 14, wherein Q is stands. 16. The method according to claim 1 for the preparation of compounds of formula I, wherein Y is C (O) X₁, n is 1 and X₁ and X is oxygen.   17. The method according to claim 1 for the preparation of compounds of formula I, wherein X-R₂ is C₃-C₆-alkenyloxy. 18. The method according to claim 1 for the preparation of 2-cyano-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) -pyr-imidinyl) - benzoic acid-1- methyl allyl ester;
<S <2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) pyrimidinyl) benzoic acid 1-methylallyl ester;
2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) -pyrimidinyl) -4-fluorobenzallylamide;
2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) pyr-imidinyl) thiobenzoic acid allyl amide;
2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) -pyrimidinyl) - benzoic acid- (1-allylaminocarbonyl-1-methyl) -ethyl ester;
<S <2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) -pyrimidinyl) -benzoic acid- (1-allylaminocarbonyl-1-methyl) -methyl ester;
2-Chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) -pyrimidinyl) - benzoic acid- (1-allyloxycarbonyl-1-methyl) -ethyl ester ;
2-Chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trichloromethyl-1 (2H) pyrimidinyl) - benzoic acid- (1-allyloxycarbonyl-1-methyl) ethyl ester ;
2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) -pyr-imidinyl) -4-fluorobenzoic acid- (1-allyloxycarbonyl-1-methyl) -ethyl ester; and
<S <2-chloro-5- (3,6-dihydro-2,6-dioxo-3-methyl-4-trifluoromethyl-1 (2H) -pyrimidinyl) -benzoic acid- (1-methylallyloxycarbonyl-1-methyl) ethyl ester. 19. The method according to claim 1, characterized in that in step a) platinum or palladium is used as the noble metal catalyst. 20. The method according to claim 19, characterized in that platinum is used. 21. The method according to claim 1, characterized in that the noble metal kata analyzer in an amount of 0.1 to 10 wt.%, Based on the aromatic used Nitro compound uses.   22. The method according to claim 20, characterized in that for modification Precious metal catalyst used in metallic or oxidized form on a support is applied. 23. The method according to claim 22, characterized in that the carrier activated carbon, Silicon dioxide in the form of silica, silica gel, aluminum oxide, calcium carbonate, Calcium phosphate, calcium sulfate, barium sulfate, titanium oxide, magnesium oxide, iron oxide, Is lead oxide, lead sulfate or lead carbonate. 24. The method according to claim 22, characterized in that the noble metal catalyst 1 contains up to 10% by weight of platinum. 25. The method according to claim 1, characterized in that the modifying phosphorus compounds are selected from the group phosphines P (R _a ) _3-p (H) _p , phosphinic acids HO-P (H) _q (R _a ) _2-q , Phosphine oxides O = P (R _a ) _3-p (H) _n , hypophosphonic acids Hypophosphorous acids O = P (OH) (H) _q (R _a ) _2-q and phosphorous acids O = P (OH) ₂H or O = P (OH) ₂R _a , where R _{a is} linear or branched C₁-C₁₂ alkyl , C₆-C₁₆ aryl or C₄-C₁₆ heteroaryl, q is 0, 1 or 2 and p is 0, 1, 2 or 3. 26. The method according to claim 1, characterized in that as a modifying Phosphorus compound diphenylphosphine, triphenylphosphine, phosphinous acid, their Salts, amides and esters, diphenylphosphinic acid, diphenylphosphite, phosphine oxides, Phosphorous acid, its salts or esters, or hypophosphorous acid, its salts or ester used. 27. The method according to claim 11, characterized in that as a modifying Phosphorus compound Phosphorous acid, its salts or esters and hypophosphorous Acid and its salts or esters used.   28. The method according to claim 1, characterized in that the modification of Precious metal catalyst with the phosphorus compound in situ before the hydrogenation. 29. The method according to claim 1, characterized in that the ratio of Noble metal catalyst to the modifying phosphorus compound 1 to 0.1 to 1 to 1000 Parts by weight. 30. The method according to claim 1, characterized in that transition metal ions from the group Fe ²⁺ , Fe ³⁺ , Ru ³⁺ , Mn ²⁺ , Mn ³⁺ , Co ²⁺ , Co ³⁺ or a vanadium compound are used as co-catalysts in which the vanadium has the oxidation state 0, II, III, IV or V. 31. The method according to claim 30, characterized in that one as a cocatalyst a vanadium compound in which the vanadium has the oxidation state 0, II, III, IV or V has, adds. 32. The method according to claim 31, characterized in that the vanadium compound in catalytic amounts is dissolved or dispersed in the reaction medium. 33. The method according to claim 31, characterized in that the vanadium compound is first applied to a suitable carrier material and in this form in Reaction medium is dispersed. 34. The method according to claim 31, characterized in that the vanadium compounds are selected from the group vanadium (III) acetylacetonate, vanadium (IV) acetylaceto nate, V₂O₅, VOCl₃, VCl₆⁻, [VO (SCN) ₄] ^2- , VOSO₄, NH₄VO₃, LiVO₃, NaVO₃, KVO₃, VCl₃, VCl₂ or the corresponding halides with F or Br. 35. The method according to claim 34, characterized in that the ammonium, Li, Na or K vanadates or a hydrate of these vanadates. 36. The method according to claim 1, characterized in that the vanadium compound dung in an amount of 1-2000 ppm, based on the aromatic to be hydrogenated Nitro compound uses.   37. The method according to claim 1, characterized in that the weight ratio of Vanadium compound to noble metal catalyst is 1 to 1 to 1 in 10,000. 38. The method according to claim 1, characterized in that process step a) a pressure of 1 to 100 bar is carried out. 39. The method according to claim 1, characterized in that the temperature at the Carrying out process step a) is 0 to + 160 ° C. 40. The method according to claim 1, characterized in that when the to be hydrogenated Compound is liquid at the reaction temperature, the hydrogenation without solvent is carried out. 41. The method according to claim 1, characterized in that in Process step c) as bases potassium tert-butylate, sodium tert-butylate, Sodium methylate, sodium ethylate, potassium methylate, potassium ethylate, sodium hydride, Potassium hydride, sodium pentylate, potassium pentylate or 1,8-diazabicyclo [5.4.0] undec- 7-en (DBU) used. 42. The method according to claim 41, characterized in that potassium tert. butylate or potassium tert-pentylate used. 43. The method according to claim 1, characterized in that in Process step c) the base in an amount of 0.25 to 0.35 equivalents in Relates to the enamine of formula IV used. 44. The method according to claim 43, characterized in that in Process step c) uses the base in an amount of 0.3 equivalents. 45. The method according to claim 1, characterized in that the Reaction according to process step c) at a temperature of 0 ° C to + 20 ° C carries out.   46. The method according to claim 45, characterized in that the Reaction carried out at a temperature of 0 ° C to + 5 ° C. 47. The method according to claim 1, characterized in that the Implementation according to process step c) in such a way by the Base in pure dimethylformamide, dimethyl sulfoxide, acetonitrile, propionitrile, Ethyl acetate, tetrahydrofuran, dioxane, N-methylpyrrolidone, methyl tert-butyl ether, Dimethylacetamid or toluene, or mixtures thereof and then the Compound of formula IV and then adds the compound of formula V.