DE3931627A1 - New amino-carbonyl-substd. iso-thiazole or isoxazole carboxylic acid d - Google Patents

Abstract

Aminocarbonyl-substd. isoxazole and isothiazole derivs. of formula (Ia)-(Id) are new: X = O or S; R1 = H; halo; 1-6C alkyl; 1-4C alkoxy or alkylthio; benzyl; phenyl; phenoxy or phenylthio; 5-6 membered, satd. or aromatic heterocycle contg. 1 or 2 O, S or N, and opt. substd. by 1 or 2 halo, 1-3C alkyl, alkoxy or alkoxycarbonyl; 3-8C cycloalkyl(1-6C)alkyl; 2-6C alkenyl or alkynyl, both opt. substd. by 1-3 halo or 1-3C alkoxy and/or by one cyclopropyl or phenyl; or 3-8C cycloalkyl or 3-6C cycloalkenyl, both opt. substd. by 1-3 1-4C alkyl or halo; R'1 = 3-8C cycloalkyl(1-6C)alkyl; 2-6C alkenyl or alkynyl as for R1, or 3-6C cycloalkenyl opt. substd. by 1-3 halo or 1-4C alkyl; R2 = HCO, 4,5-dihydrooxazol-2-yl, COYR5 or CONR6R7; Y = O or S; R5 = H; 1-6C alkyl; R3 = H, 1-6C alkyl; R4 = H; OH, 1-4C alkoxy; 1-6C alkyl, etc., their environmentally acceptable salts are included.

Description

The present invention relates to carboxamides of the formulas Ia, Ib and IC

in which the substituents have the following meaning:
X oxygen or sulfur;
R¹ is hydrogen; Halogen; C₁-C₆-alkyl which may carry one to five halogen atoms and / or one or two of the following radicals: cyclopropyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio or cyano ;
Benzyl substituted one to three times by C₁-C₄alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio, halogen, cyano or nitro can be;
C₃-C₈-cycloalkyl which may be substituted one to three times by C₁-C₄-alkyl or halogen;
C₂-C₆-alkenyl, which may be substituted one to three times by halogen or C₁-C₃ alkoxy and / or once by phenyl, wherein the phenyl radical in turn may carry one to three of the following groups: C₁-C₄-alkyl, C₁- C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio, halogen, cyano or nitro;
C₂-C₆ alkynyl which may be substituted one to three times by halogen or C₁-C₃ alkoxy and / or once by phenyl, the phenyl radical in turn may carry one to three of the following groups: C₁-C₄-alkyl, C₁- C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio, halogen, cyano or nitro;
C₁-C₄ alkoxy; C₁-C₄-alkylthio; C₁-C₄-haloalkoxy; C₁-C₄-haloalkylthio;
Phenoxy or phenylthio which is one to three times by C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio, halogen, cyano or Nitro may be substituted;
a 5- to 6-membered saturated or aromatic heterocyclic radical containing one or two heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen which may carry one or two of the following substituents: C₁-C₃alkyl, halogen, C₁-C₃alkoxy and C₁-C₃ alkoxycarbonyl;
Phenyl which may carry one to three of the following groups: C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkyl, C₁-C₆-alkylthio, C₁-C₆-haloalkylthio, halogen, Nitro and cyano;
R² is formyl, 4,5-dihydrooxazol-2-yl, a COYR⁵ radical or a CONR⁶R⁷ radical;
Y oxygen or sulfur;
R⁵ hydrogen; C₁-C₆-alkyl which may carry one to five halogen atoms and / or one of the following radicals: hydroxy, C₁-C₄alkoxy, C₂-C₄alkoxy-C₁-C₄alkoxy, cyano, trimethylsilyl, C₁-C₃alkylthio , C₁-C₃alkylamino, di-C₁-C₃alkylamino, C₃-C₆cycloalkylamino, di-C₃-C₆cycloalkylamino, C₁-C₃alkylsulfinyl, C₁-C₃alkylsulfonyl, carboxyl, C₁-C₃alkoxycarbonyl, di C₁-C₃-alkylaminocarbonyl, di-C₁-C₃-alkoxyphosphonyl, C₁-C₃-alkaniminoxy, thienyl, furanyl, tetrahydrofuranyl, N-phthalimido, pyridyl, benzyloxy, benzoyl, where these cyclic radicals may carry one to three of the following groups: C₁-C₃alkyl, C₁-C₃alkoxy or halogen;
Benzyl which may carry one to three of the following groups: C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, halogen, nitro and cyano;
C₃-C₈ cycloalkyl;
Phenyl which may carry one to three of the following groups: C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ alkoxycarbonyl, halogen, nitro and cyano;
C₃-C₆ alkenyl, C₅-C₆-cycloalkenyl, C₃-C₆ alkynyl, where these radicals may carry one of the following groups: hydroxy, C₁-C₄ alkoxy, halogen or phenyl, wherein the phenyl radical in turn one to three of the following groups C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkyl, halogen, nitro and cyano;
a five- to six-membered heterocyclic radical having one or two heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen or a benzotriazole radical;
phthalimido; tetrahydrophthalimido; succinimido; maleimido;
one equivalent of a cation from the groups of the alkali or alkaline earth metal, manganese, copper, iron, ammonium and substituted ammonium or a radical -N = CR⁸R⁹;
R⁸, R⁹ is hydrogen, C₁-C₄-alkyl; C₃-C₆ cycloalkyl; phenyl; furyl; or together a methylene chain with 4 to 7 members;
R⁶ hydrogen; C₁-C₆-alkyl or C₃-C₈-cycloalkyl and
R⁷ hydrogen; C₁-C₆ alkyl or
R⁶, R⁷ together form a methylene chain with 4 to 5 members;
R3 is hydrogen; C₁-C₆-alkyl which may carry one to three of the following substituents: hydroxy, halogen, C₁-C₄-alkoxy, C₁-C₄-alkylthio or di-C₁-C₄-alkylamino;
C₃-C₈-cycloalkyl which may be substituted one to three times by C₁-C₄-alkyl, halogen and C₁-C₄-haloalkyl;
R⁴ hydrogen; hydroxy; C₁-C₄ alkoxy;
C₁-C₆-alkyl which may carry one to three of the following groups: C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio, di-C₁-C₄-alkylamino, halogen, C₃-C₈-cycloalkyl or phenyl, wherein the phenyl ring in turn may carry one to three of the following radicals: halogen, cyano, nitro, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy C₁-C₄-alkylthio or C₁-C₄-haloalkylthio;
C₃-C₈-cycloalkyl which may carry one to three of the following groups: C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, halogen, nitro or cyano;
C₃-C₆-alkenyl, which may be substituted one to three times by halogen and / or once by phenyl, wherein the phenyl radical in turn may carry one to three of the following groups: C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁- C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio, halogen, cyano or nitro;
C₃-C₆-alkynyl which may be substituted one to three times by halogen and / or once by phenyl, wherein the phenyl radical in turn may carry one to three of the following groups: C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁- C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio, halogen, cyano or nitro;
Di-C₁-C₄-alkylamino;
a 5- to 6-membered heterocyclic saturated or aromatic radical having one or two heteroatoms selected from the group consisting of oxygen, sulfur or nitrogen, which may be substituted one to three times by C₁-C₄-alkyl or halogen;
Phenyl which may carry one to four of the following groups: C₁-C₄alkyl, C₁-C₄haloalkyl, C₁-C₄alkoxy, C₁-C4-haloalkoxy, C₁-C₄alkylthio, C₁-C₄-haloalkylthio, halogen, Nitro, cyano, formyl, C₁-C₄-alkanoyl, C₁-C₄-haloalkanoyl or C₁-C₄-alkoxycarbonyl;
Naphthyl, which may be substituted one to three times by C₁-C₄-alkyl or halogen;
or
R³, R⁴ together form a C₄-C₇-methylene chain which may be interrupted by oxygen, sulfur or N-methyl or the radical - (CH₂) ₃-CO-,
where R³ and R⁴ are not simultaneously hydrogen, when

• - R¹ is hydrogen, methyl or phenyl and R² is CONH₂, CO₂H or CO₂CH₃ means or if
• X is oxygen, R¹ is CH (OCH₂CH₃) ₂ and R² is CONH₂,

as well as their environmentally compatible salts.  

Moreover, the invention relates to processes for the preparation of the compounds Ia, Ib and Ic and herbicidal agents which contain at least one compound Ia ', Ib 'or Ic', in which the substituents are those given above Have meaning and R³ and R⁴ can simultaneously be hydrogen, if

• - R¹ is hydrogen, methyl or phenyl and R² is CONH₂, CO₂H or CO₂CH₃ means or if
• X is oxygen, R¹ is CH (OCH₂CH₃) and R² is CONH₂.

From the literature, the following carboxylic acid amides of type IA, IB and IC known.

However, their use as herbicides has not been described.  

Object of the present invention was to provide new herbicidal active Find and synthesize compounds.

Accordingly, the above-defined carboxylic acid amides Ia, Ib and Ic found.

In addition, there have been processes for their preparation and their containing herbicidal agent found.

The carboxylic acid amides Ia, Ib and Ic according to the invention are available various ways to produce. You get them for example after the following procedures:

1. A process for the preparation of compounds of formulas Ia and IB, in R² is CO₂CH₃ and X is oxygen

The carboxylic acid amides Ia and Ib are obtained by reacting a hydroxyamino acid chloride II in a conventional manner with a β-ketoester III reacts, the resulting dimethyl diester IV then initially with one equivalent of an aqueous base to the monoesters Va or Vb hydrolyzed and Va and Vb then separately or in a mixture first in known manner in the halides or other activated forms of Carboxylic acids and then these derivatives with an amine VI amidated.

The individual reaction steps A, B and C of this synthesis sequence can be carried out as follows:

Reaction step A

The reaction is usually at temperatures of 0 to 50 ° C, preferably 10 to 30 ° C in an inert aprotic polar organic solvent in the presence of a base.

Suitably used as the solvent hydrocarbons such as in particular Benzene and toluene or ethers such as diethyl ether, tetrahydrofuran and Ethylene glycol dimethyl ether.

Sodium hydride is particularly suitable as the base.

The reaction is usually carried out so that first of the β-ketoester III in the solvent with 1 to 2 mol eq. the base in the anion is transferred. This solution of the anion of III is then with a solution of II and left at the reaction temperature.

The reaction is generally completed after 4 to 12 hours.

Before working up the products, it is recommended that in the reaction to remove formed water azeotrope.

Reaction step B

The partial saponification of dimethyl diester IV to monoester Va and Vb is usually at temperatures from -40 to 20 ° C, preferably -20 to 0 ° C, in an inert, water-miscible organic solvent in Presence of 1 to 1.2 mol eq. a base performed.

Suitable bases are in particular hydroxides of alkali metal cations. The base is generally used as a 5 to 10 percent aqueous solution added.

Preferred solvents for this reaction are, for example, tetrahydrofuran and dioxane.

For workup, the reaction mixture is usually acidified, wherein the desired product separates out as a solid or as an oil. The Isolation takes place in the usual way by filtration or extraction.  

The mixture of the two isomeric monoesters Va and Vb can be fractionated by Crystallization or be separated by chromatographic means or it can be further implemented without separation.

Reaction step C

The compounds Ia and Ib are obtained from the monoesters Va and Vb, in the Va and Vb first in a conventional manner in the halide or another activated form of the carboxylic acid function is converted and these derivatives are then amidated with an amine VI.

Activated forms of the carboxylic acid are in addition to halides such as in particular the chlorides and the bromides, for example, imidazolides. in the In general, the halides are preferred.

They are obtained by reacting the carboxylic acids Va and Vb with a Halogenating agents such as thionyl chloride, thionyl bromide, phosphorus oxychloride or bromide, phosphorus tri- and pentachloride or bromide and elemental chlorine and bromine.

The halogenating agent is used in 1 to 5 mol-eq., Preferably 1 to 2 mol eq., Used.

The reaction proceeds at temperatures from 20 ° C to the boiling point of Halogenating agent or if one in the presence of an inert organic solvent works, even its boiling point.

Suitable solvents are, for example, hydrocarbon and Halogenated hydrocarbons such as benzene, toluene and dichloromethane.

Usually, the activated carboxylic acid derivatives are isolated, for example by distilling off the halogenating agent and if so present the solvent and only then with the amines VI implemented.

In this case, the amidation at temperatures from -20 to 50 ° C, preferably 0 to 30 ° C in an inert aprotic polar organic Solvent carried out.

Halogenated hydrocarbons, in particular, are suitable for this reaction Dichloromethane and ethers such as diethyl ether and tert-butyl methyl ether as Solvent.  

Since formed in the amidation of acid halides hydrogen halide It is recommended, the amine VI in 2 to 5 mol-eq. Excess, preferably 2 to 3 mol-eq. add. Unless the amine is in equimolar Amounts (1 to 1.2 mol eq.) Is used to bind the hydrogen halide a base, especially a tertiary amine such as triethylamine or pyridine are added.

If one starts from a mixture of monoesters Va and Vb, one obtains in the reaction, a mixture of the isomeric carboxylic acid amides Ia and Ib. This mixture can in a conventional manner, for example by fractionated crystallization or chromatography in the individual components be separated.

2. A process for the preparation of the compounds Ia in which X is oxygen, R² CO₂R₅ and R⁵ is not hydrogen or methyl

In analogy to the process described under 1. one obtains this Compounds Ia, by reacting a Hydroxyamsäurechlorid II in the above reacting manner with a β-keto ester of the formula IIIa, the so obtained diester IVa then with a saponification in the Monoester V 'splits and activates this and amidiert to Ia.

The reaction steps A and C this synthesis sequence are in general and in particular according to the conditions described in FIGS. 1A and 1C carried out.  

Reaction step B

The partial saponification of dimethyl diester IVa to monoester V 'becomes usually at temperatures of -40 to 20 ° C, preferably -20 to 0 ° C, carried out in an inert organic solvent.

The saponification reagent depends on the type of ester. As saponification reagent For example, hydroxides of alkali metal Cations for unbranched alkyl esters, mineral acids for α-branched Alkyl esters and hydrogen in the hydrogenolysis of benzyl and Allyl.

These methods are well known and can be used in accordance with the methods described in US Pat Literature described conditions.

As far as in this type of synthesis with a hydroxamic acid IIa with If a β-ketoester III converts, it is also possible in the same way specifically to prepare the compounds Ib in which X is oxygen, R² CO₂R⁵ and R⁵ does not denote hydrogen or methyl.

The latter method for the targeted production of an isomer of Both carboxylic acid amides Ia and Ib are based on the possibility of two different ester groups of a compound by use only one mole equivalent of saponification reagent under mild reaction conditions to selectively cleave the one ester group.

3. Process for the preparation of the compounds Ia and Ic, in which R¹ not hydrogen and R² is carboxyl or formyl and R³ is hydrogen mean

These isomeric carboxylic acid amides Ia and Ic are obtained by reacting a Carboxylic acid Vc or Vd according to the conditions described under 1C activated amidated and then the amides VIIa or VIIb thus obtained in a manner known per se in the presence of a carboxylating reagent or a Formylierungsreagens.

The reaction step A of this synthesis sequence is in general and in particular according to those described in the method 1 under point C. Conditions performed.

Reaction step B

The formylation or carboxylation of the carboxamides VIIa or VIIb usually takes place at temperatures of -100 to -20 ° C, preferably -80 to -40 ° C in an aprotic polar inert organic solvent with the exclusion of moisture in the presence of a base.

The formylating reagent used is in particular dimethylformamide and N-formylmorpholine, preferred carboxylating agent is carbon dioxide.

Suitable solvents are in particular diethyl ether, tert-butyl methyl ether, Tetrahydrofuran and dioxane.

Preferred bases are alkali metal hydrocarbons, such as methyllithium, n-butyllithium, tert-butyllithium and phenyllithium use.

The reaction is usually carried out so that first a solution of the carboxamide VIIa or VIIb with 2 to 2.5 mol eq. the solved one Base is added, wherein a metallated in the ring Carbonsäureamidderivat is formed, which in the subsequent addition of the electrophilic Formylierungs- or Carboxylierungsreagens' to the desired product Ia or Ic reacted.  

The carboxylic acids X required for this process are known from the literature (Beilstein, Hauptwerk and 1-5 Supplementary Works, Volume 27, R.W. Wiley, The Chemistry of Heterocyclic Compounds, Five- and Six-Membered Compounds with Nitrogen and Oxygen, Interscience Publishers, New York, London (1962)) or can by generally literature methods, eg. B. by Oxidation from the corresponding alcohols or aldehydes or by Hydrolysis be prepared from the corresponding nitriles.

The corresponding compounds Ib in which X is oxygen are according to the above-described method only in low yields accessible, wherein also the carboxylation or formylation at Temperatures of <-80 ° C should be carried out.

The compounds Ib in which X is oxygen and R 2 is CO₂H, but particularly advantageous according to the following methods:

The reaction steps A and C are in general and in particular analogous to those described above in method 2 under point B. Conditions performed; the reactions B are carried out according to the Procedure 1 conditions described under point C.

The reaction is carried out by reacting a dicarboxylic acid dialkyl ester X at temperatures between 0 and 80 ° C, preferably between 0 and 40 ° C, in an organic solvent, for. As methanol or ethanol, with or ethanol, with a strong base, e.g. As NaOH, KOH or Ca (OH) ₂, treated. In general, about 1 equivalent of the strong base in used aqueous solution. After the reaction is cooled and with a strong mineral acid, eg. Hydrochloric acid or sulfuric acid, acidified. The resulting carboxylic acid XIII can in the usual way and Way z. B. by suction or by extraction with an organic Solvent be isolated.  

For the conversion of the carboxylic acid XI in the carboxylic acid halide is brought the acid XI in the usual manner with an inorganic acid halide, such as thionyl chloride, phosphorus tri- or phosphorus pentahalides, to the reaction, wherein the chlorides are preferred. It is expediently the inorganic acid halide in 1 to 5 molar equivalents, preferably 1 to 2 molar equivalents used. You can do without solvents or in the presence of an inert organic solvent such as. B. benzene or toluene at temperatures between room temperature and the boiling point of the inorganic acid halide or of the inert organic Solvent work. In some cases, the addition of a Catalyst, such as dimethylformamide or 4-Dimethylaminpyridion of Be an advantage. After completion of the reaction, the acid halide can usual way to be isolated, for. B. by distilling off the Excess of inorganic acid halides and organic solvent and subsequent distillation of the acid chloride at normal pressure or reduced pressure.

The carboxylic acid amides XIIa are obtained from the carboxylic acid halides Reaction with an amine VI. It is expediently done so that the carboxylic acid halide in an inert organic solvent such as dichloroethane, or an ether such as diethyl ether or methyl tert. butyl ether with an amine XV, also dissolved in an organic Solvent, brings to reaction. It is expedient to use the amine VI in 2- to 5-fold molar amount, preferably 2 to 3 times molar amount to bind the resulting hydrogen halide. you can also in the presence of an auxiliary base such as a tertiary amine, for. B. Triethylamine, work. In this case, suffice 1 to 5.5 molar equivalents Amine VI. The reaction temperature may be between 0 and 50 ° C, preferably between 0 and 20 ° C. The reaction is generally from 1 to 12 hours ended. The mixture can be worked up as usual, for example, by hydrolysis with water and extraction of the product of Formula XIIa with an organic solvent and concentration of the organic solvent. For purification, the product of formula XIIa for example recrystallized or chromatographed.

From the 4-alkoxycarbonyl-isoxazole-5-carboxamides XIIa can be the free carboxylic acids XIIb by reaction with aqueous bases and subsequent reaction with mineral acids. The reaction will be like this carried out that the ester XIIa at temperatures between 0 and 80 ° C, preferably between 0 and 50 ° C, in an organic solvent such as z. For example, methanol or ethanol with a base such as. As NaOH, KOH or Ca (OH) ₂ treated. In general, about 1 to 3 equivalents, preferably 1 to 1.5 equivalents of the strong base used in aqueous solution.  After the reaction is under cooling with a strong Mineral acid, e.g. As hydrochloric acid or sulfuric acid, acidified. The resulting Carboxylic acids XIIb can be obtained by suction or by extraction with an organic solvent and concentration of this organic Be isolated solvent. For further purification of the acids XIIb These can be recrystallized or chromatographed.

The isoxazole-4,5- required as starting material for this process dicarboxylic acid dialkyl esters X are known from the literature (J. Org. Chem. 43, 3736 (1978); Chem. Pharm. Bull. 28, 3296 (1980); Tetrahedron 30, 1365 (1974)) or can be prepared by methods generally known from the literature.

The dicarboxylic acid diamides of the formula Ib in which R² = CONR'R '' with R ', R "≠ H is obtained by reacting the acids XIIb with a primary Amine VI in the presence of a dehydrating agent (e.g., propanephosphonic anhydride or dicyclohexylcarbodiimide) at a temperature between -20 and 50 ° C, preferably between 20 and 40 ° C in an inert organic solvents such as dichloromethane or an ether such as diethyl ether or methyl tert-butyl ether. The starting materials are roughly Stoichiometric amount reacted. The mixture can be as usual be worked up, for example by hydrolysis with water, extraction the product of formula XIII with an organic solvent and Concentrate this organic solvent. For further cleaning can the product of formula XIII, for example recrystallized or chromatographed become.

From the resulting Isoxazoldicarbonsäure-4,5-diamides of the formula Ib, in X = O, R² = CONR'R "and R ', R" ≠ H, the carboxylic acids Ib (R 2 = COOH) by reaction with excess potassium tert-butoxide produce. It is expediently done so that the Diamid XIII in an inert organic solvent such as diethyl ether or tetrahydrofuran at temperatures of 0 to 30 ° C, preferably at room temperature, with potassium tert-butoxide in water (ratio 3 to 6: 1) added. The reaction is generally complete after 1 to 12 hours. The free carboxylic acid Ib (R² = COOH) can after acidification with mineral acid either by suction or by extraction with an organic Solvent and concentration of this organic solvent isolated become. For further purification, the acids Ic (R² = COOH) can either recrystallized or chromatographed.

The isoxazole-4,5- required as starting material for this process dicarboxylic acid dialkyl esters X are known from the literature (J. Org. Chem. 43, 3736 (1978); Chem. Pharm. Bull. 28, 3296 (1980); Tetrahedron 30, 1365 (1974)) or can be prepared by methods generally known from the literature.  

4. A process for the preparation of the compounds Ia and Ib, in which R² is a Carboxyl group and X is sulfur

These carboxylic acid amides Ia and Ib are obtained particularly advantageously by one Isothiazoldicarbonsäureanhydrid VIII in a conventional manner reacted with an amine VI and the resulting mixture of isomers Ia and Ib separates into the individual components.

The reaction is usually carried out at temperatures of -10 to 50 ° C, preferably 0 to 30 ° C in an inert aprotic polar organic Solvent carried out.

In particular, find as solvents halogenated hydrocarbons such as Methylene chloride and ethers such as diethyl ether, tert-butyl methyl ether and Tetrahydrofuran application.

The amine VI is generally in equimolar amounts or in excess, preferably in amounts of 1 to 1.2 mol eq. used based on VIII.

In this process, the isomeric carboxylic acid amides of the formulas are formed Ia and Ib in different amounts. The separation of the isomer mixture succeeds either by fractionated crystallization or on chromatographic ways.

The isothiazoledicarboxylic anhydrides VIII required for this process are known or can be prepared by known methods (Beilstein, Hauptwerk and 1 - 5 Supplementary Works, Volume 27).  

5. A process for the preparation of the compounds Ia, Ib and Ic, in which R² CO₂H means

These compounds Ia, Ib and Ic are obtained by reacting a corresponding Ester Ia, Ib or Ic, in which R² is a group CO₂R⁵ and R⁵ C₁-C₄-alkyl, in a conventional manner in the presence of a hydrolyzed aqueous base.

This ester hydrolysis will generally and in particular be appropriate carried out under the conditions described in method 2 under point B.

6. Process for the preparation of compounds Ia, Ib and Ic, in which R² COYR⁵ or CONR⁶R⁷ means

These carboxylic acid amides Ia, Ib and Ic are obtained by reacting the corresponding Carboxylic acid Ia, Ib or Ic (R² = CO₂H) according to the in 1C described method first activated and then with a Compound IX or derivatized with an amine VI. The implementation is in following reaction scheme shown only for the carboxylic acid amides Ia.

The esterification of the carboxylic acid according to reaction route A is usually at Temperatures from 0 to 50 ° C, preferably 20 to 40 ° C in an inert aprotic polar organic solvent either via activation according to the conditions described at 1C or in the presence of an acid or a dehydrating agent performed.  

Appropriately used as the solvent halohydrocarbons such Dichloromethane and ethers such as diethyl ether, tert-butyl methyl ether and Tetrahydrofuran.

As dehydrating agent (condensing agent) is particularly suitable Dicyclohexylcarbodiimide and propanephosphonic anhydride.

7. Process for the preparation of the compounds Ia, Ib and Ic, in which R² is 4,5-dihydrooxazol-2-yl

The compounds are obtained by reacting the carboxylic acid amides of Formula Ia, Ib and Ic, in which R² is COOH or COOR⁵ (R⁵ = C₁-C₄-alkyl), in a conventional manner with an aminoalcohol the formula X implements

The reaction is carried out by reacting the compounds at 0 to 180 ° C, preferably at the reflux temperature of the mixture used with an aminoalcohol X, optionally in the presence of an inert Solvent, reacted. Ester or carboxylic acid Ia, Ib and Ic and aminoalcohol V are in the ratio 1: 1 to 1: 2.5, preferably 1: 1 used up to 1: 1.5.

The solvents used are expediently halogenated hydrocarbons such as chlorobenzene and 1,2-dichlorobenzene, ethers, e.g. Methyl tert-butyl ether, 1,2-dimethoxyethane, diethylene glycol dimethyl ether, Tetrahydrofuran and dioxane; Alcoholates such as methanol, ethanol, propanol or ethylene glycol, dipolar aprotic solvents, e.g. Acetonitrile, Dimethylformamide, dimethylacetamide, dimethyl sulphoxide, N-methylpyrrolidone, 1,3-dimethyltetrahydro-2 (1H) -pyrimidinone and 1,3-dimethylimidazolin-2-one or aromatics, e.g. As benzene, toluene and Xylene. The concentration of the educts in the solvent is in general 0.1 to 5.0 mol / l, preferably 0.2 to 2.0 mol / l.  

The reaction is generally complete after 14 hours; the Oxazolines Ia, Ib and Ic are then optionally by addition of Water precipitated, filtered off with suction or with an organic solvent extracted and by standard methods such as recrystallization or purified by chromatography.

8. A process for the preparation of the compounds Ib in which R² is formyl means

These compounds Ib are obtained, for example, by adding a corresponding carboxylic acid amide of the formula Ib in which R² is a group CO₂H means according to the conditions described in method 1 activated and the resulting activated form of the carboxylic acid in reduced known manner.

Preferably, the carboxylic acid is converted into the corresponding one Chloride and reduces this carboxylic acid chloride at temperatures of -100 to 0 ° C, especially -80 to -50 ° C with a complex hydride such as, in particular, lithium tri-tertiary-butylaluminum hydride. When Solvents in this case particularly preferably serve ethers, such as ethyl ether, tetrahydrofuran, 1,2-dimethoxyethane, diethylene glycol and Dioxane, (J. Am. Chem. Soc., 80, 5372 (1958); J. Am. Chem. Soc., 80, 5377) (1958)).

In addition to the above-described methods 1-8 for the preparation of Compounds Ia, Ib and Ic, there are other synthetic possibilities that the The following references can be found:

Beilstein, Hauptwerk and 1.-5. Supplementary work, volume 27;
RW Wiley, The Chemistry of Heterocyclic Compounds, Five- and Six-Membered Compounds with Nitrogen and Oxygen, Interscience Publishers, New York, London (1962);
AR Katritzky, CW Rees, Complementary Heterocyclic Chemistry, Vol. 6, Five-membered Rings with Two or More Oxygen, Sulfur or Nitrogen Atoms, Pergamon Press, 1984;
J. March, Advanced Organic Chemistry, Third Edition, John Wiley and Sons, 1985;
Houben-Weyl, Methods of Organic Chemistry, 4th Edition, Thieme Verlag, Volumes IV, VI, VII, VIII, X.

With regard to the intended use of the compounds Ia, Ib and Ic, preference is given to the following radicals as substituents:
X oxygen or sulfur,
R¹ is hydrogen,
Halogen such as fluorine, chlorine, bromine, iodine, in particular fluorine or chlorine;
Alkyl such as methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 1,1-dimethylpropyl, 1, 2-dimethylpropyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,2-dimethylbutyl, 2,3-dimethylbutyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,1,2-trimethylpropyl, 1,2,2-trimethylpropyl, 1-ethyl-1-methylpropyl and 1-ethyl-2-methylpropyl, in particular methyl, ethyl, propyl, 1-methylethyl and 1,1-dimethylethyl, which contains one to five halogen atoms such as fluorine, chlorine, bromine, iodine, in particular fluorine and chlorine, and / or one or two of the following radicals: cyano; cyclopropyl; Alkoxy such as methoxy, ethoxy, propoxy, 1-methylethoxy, butoxy, 1-methylpropoxy, 2-methylpropoxy and 1,1-dimethylethoxy, especially methoxy, ethoxy, 1-methylethoxy and 1,1-dimethylethoxy; Haloalkoxy such as difluoromethoxy, trifluoromethoxy, chlorodifluoromethoxy, dichlorofluoromethoxy, 1-fluoroethoxy, 2-fluoroethoxy, 2,2-difluoroethoxy, 1,1,2,2-tetrafluoroethoxy, 2,2,2-trifluoroethoxy, 2-chloro-1,1, 2-trifluoroethoxy and pentafluoroethoxy, especially trifluoromethoxy and pentafluoroethoxy; Alkylthio such as methylthio, ethylthio, propylthio, 1-methylethylthio, n-butylthio, 1-methylpropylthio, 2-methylpropylthio and 1,1-dimethylethylthio, especially methylthio and ethylthio; Haloalkylthio, such as difluoromethylthio, trifluoromethylthio, chlorodifluoromethylthio, 1-fluoroethylthio, 2-fluoroethylthio, 2,2-difluoroethylthio, 2,2,2-trifluoroethylthio, 2-chloro-2,2-difluoroethylthio, 2,2-dichloro-2-fluoroethylthio, 2,2,2-trichloroethylthio and pentafluoroethylthio, especially trifluoromethylthio and pentafluoroethylthio;
Benzyl which is one to three times by alkyl having 1 to 4 carbon atoms as mentioned above, in particular methyl, ethyl and 1-methylethyl; Haloalkyl as mentioned above, in particular trifluoromethyl and chlorodifluoromethyl; Alkoxy as mentioned above, in particular methoxy and ethoxy; Haloalkoxy as mentioned above, in particular trifluoromethoxy, trichloromethoxy and pentafluoroethoxy; Alkylthio as mentioned above, in particular methylthio and ethylthio; Haloalkylthio as mentioned above, in particular difluoromethylthio, trifluoromethylthio and pentafluoromethylthio; Halogen as mentioned above, in particular fluorine and chlorine; Cyano or nitro may be substituted;
C₃-C₈cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and cyclooctyl, in particular cyclopropyl, cyclopentyl and cyclohexyl; the one to three times by alkyl as mentioned above, in particular methyl and ethyl; or halogen as mentioned above, in particular fluorine and chlorine, may be substituted;
Alkenyl such as ethenyl, 1-propenyl, 2-propenyl, 2-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-methyl-1-propenyl, 1-methyl-2-propenyl, 2-methyl-1 propenyl, 2-methyl-2-propenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 1-methyl-1-butenyl, 2-methyl-1-butenyl, 3-methyl-2-butenyl, 1-methyl-2-butenyl, 2-methyl-2-butenyl, 1-methyl-3-butenyl, 2-methyl-3-butenyl, 3-methyl-3-butenyl, 1,1-dimethyl-2-propenyl, 1,2-dimethyl-2-propenyl, 1-ethyl-1-propenyl, 1-ethyl-2-propenyl, 1-hexenyl, 2-hexenyl, 3-hexenyl, 4-hexenyl, 5-hexenyl, 1-methyl 1-pentenyl, 2-methyl-1-pentenyl, 3-methyl-1-pentenyl, 4-methyl-1-pentenyl, 1-methyl-2-pentenyl, 2-methyl-2-pentenyl, 3-methyl-2- pentenyl, 4-methyl-2-pentenyl, 1-methyl-3-pentenyl, 2-methyl-3-pentenyl, 3-methyl-3-pentenyl, 4-methyl-3-pentenyl, 1-methyl-4-pentenyl, 2-methyl-4-pentenyl, 3-methyl-4-pentenyl, 4-methyl-4-pentenyl, 1,1-dimethyl-2-butenyl, 1,1-dimethyl-3-butenyl, 1,2-dimethyl 1-butenyl, 1,2-dimethyl-2-butenyl, 1,2-dimethyl-3-butenyl, 1, 3-dimethyl-1-butenyl, 1,3-dimethyl-2-butenyl, 1,3-dimethyl-3-butenyl, 2,2-dimethyl-3-butenyl, 2,3-dimethyl-1-butenyl, 2, 3-Dimethyl-2-butenyl, 2,3-dimethyl-3-butenyl, 3,3-dimethyl-1-butenyl, 1-ethyl-1-butenyl, 1-ethyl-2-butenyl, 1-ethyl-3 butenyl, 3-ethyl-1-butenyl, 2-ethyl-2-butenyl, 2-ethyl-3-butenyl, 1,1,2-trimethyl-2-propenyl, 1-ethyl-1-methyl-2-propenyl, 1-ethyl-2-methyl-1-propenyl and 1-ethyl-2-methyl-2-propenyl, especially ethenyl, 1-propenyl, 2-propenyl, 1-methylethenyl, 1-butenyl, 2-butenyl, 3-butenyl , 1-methylpropenyl, 1-methyl-2-propenyl, 2-methyl-1-propenyl, 2-methyl-2-propenyl, which is one to three times by halogen as mentioned above, in particular fluorine and chlorine; or alkoxy as mentioned above, in particular methoxy and ethoxy; and / or may be substituted once by phenyl, wherein the phenyl radical in turn may carry one to three of the following groups; Alkyl as mentioned above, in particular methyl, ethyl and 1-methylethyl; Haloalkyl as mentioned above, in particular trifluoromethyl and chlorodifluoromethyl; Alkoxy as mentioned above, in particular methoxy and ethoxy; Haloalkoxy as mentioned above, in particular trifluoromethoxy, trichloromethoxy and pentafluoroethoxy; Alkylthio as mentioned above, in particular methylthio and ethylthio; Haloalkylthio as mentioned above, in particular difluoromethylthio, trifluoromethylthio and pentafluoromethylthio; Halogen as mentioned above, in particular fluorine and chlorine; Cyano or nitro;
Alkynyl, such as ethynyl, 1-propynyl, propargyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-methyl-2-propynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-methyl- 3-butynyl-2-methyl-3-butynyl, 1-methyl-2-butynyl, 3-methyl-1-butynyl, 1,1-dimethyl-2-propynyl, 1-ethyl-2-propynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-methyl-2-pentynyl, 1-methyl-3-pentynyl, 1-methyl-4-pentynyl, 3-methyl-1-pentynyl, 3 Methyl 4-pentynyl, 4-methyl-1-pentynyl, 4-methyl-2-pentynyl, 1,1-dimethyl-2-butynyl, 1,1-dimethyl-3-butynyl, 1,2-dimethyl-3- butinyl, 2,2-dimethyl-3-butynyl, 3,3-dimethyl-1-butynyl, 1-ethyl-2-butynyl, 1-ethyl-3-butynyl, 2-ethyl-3-butynyl and 1-ethyl 1-methyl-2-propynyl, in particular ethynyl, 1-propynyl and propargyl, which is one to three times by halogen as mentioned above, in particular iodine; or alkoxy as mentioned above, in particular methoxy and ethoxy; and / or may be substituted once by phenyl, wherein the phenyl radical in turn may carry one to three of the following groups: alkyl as mentioned above, in particular methyl, ethyl and 1-methylethyl; Haloalkyl as mentioned above, in particular trifluoromethyl and chlorodifluoromethyl; Alkoxy as mentioned above, in particular methoxy and ethoxy; Haloalkoxy as mentioned above, in particular trifluoromethoxy, trichloromethoxy and pentafluoroethoxy; Alkylthio as mentioned above, in particular methylthio and ethylthio; Haloalkylthio as mentioned above, in particular difluoromethylthio, trifluoromethylthio and pentafluoromethylthio; Halogen as mentioned above, in particular fluorine and chlorine; Cyano or nitro;
C₁-C₄-alkoxy as mentioned above, in particular methoxy and ethoxy;
C₁-C₄-haloalkoxy as mentioned above, in particular trifluoromethoxy, trichloromethoxy and pentafluoroethoxy;
C₁-C₄-alkylthio as mentioned above, in particular methylthio and ethylthio;
C₁-C₄-haloalkylthio as mentioned above, in particular difluoromethylthio, trifluoromethylthio and pentafluoroethylthio;
Phenoxy or phenylthio which is substituted one to three times by alkyl as mentioned above, especially methyl, ethyl and 1-methylethyl; Haloalkyl as mentioned above, in particular trifluoromethyl and chlorodifluoromethyl; Alkoxy as mentioned above, in particular methoxy and ethoxy; Haloalkoxy as mentioned above, in particular trifluoromethoxy, trichloromethoxy and pentafluoroethoxy; Alkylthio as mentioned above, in particular methylthio and ethylthio; Haloalkylthio as mentioned above, in particular difluoromethylthio, trifluoromethylthio and pentafluoromethylthio; Halogen as mentioned above, in particular fluorine and chlorine; Cyano or nitro; may be substituted;
a 5- to 6-membered saturated or aromatic heterocyclic radical containing one or two heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, such as 2-tetrahydrofuranyl, 3-tetrahydrofuranyl, 2-tetrahydrothienyl, 3-tetrahydrothienyl, 2-tetrahydropyranyl, 3-tetrahydropyranyl , 4-tetrahydropyranyl, 2-furanyl, 3-furanyl, 2-thienyl, 3-thienyl, 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 2-oxazolyl, 4 -Oxazolyl, 5-oxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl, 2-pyrrolyl, 3-pyrrolyl, 3-pyrazolyl, 4-pyrazolyl, 5-pyrazolyl , 2-pyridyl, 3-pyridyl and 4-pyridyl, which may carry one or two of the following substituents: alkyl as mentioned above, in particular methyl; Halogen as mentioned above, in particular fluorine and chlorine; Alkoxy as mentioned above, in particular methoxy and ethoxy; or alkoxycarbonyl, such as methoycarbonyl and ethoxycarbonyl, in particular methoxycarbonyl;
Phenyl which may carry one to three of the following groups: alkyl as mentioned above, in particular methyl, ethyl, and 1-methylethyl; Haloalkyl as mentioned above, in particular trifluoromethyl and chlorodifluoromethyl; Alkoxy as mentioned above, in particular methoxy and ethoxy; Haloalkoxy as mentioned above, in particular trifluoromethoxy, trichloromethoxy and pentafluoroethoxy; Alkylthio as mentioned above, in particular methylthio and ethylthio; Haloalkylthio as mentioned above, in particular difluoromethylthio, trifluoromethylthio and pentafluoromethylthio; Halogen as mentioned above, in particular fluorine and chlorine; Cyano or nitro;
R² is formyl, 4,5-dihydrooxazol-2-yl, a COYR⁵ radical or a CONR⁶R⁷ radical;
Y oxygen or sulfur;
R⁵ hydrogen;
Alkyl as mentioned for R¹, in particular methyl, ethyl, propyl, 1-methylethyl and hexyl; which may carry one to five halogen atoms as mentioned under R¹, in particular fluorine and chlorine, and / or one of the following radicals: hydroxy; Alkoxy as mentioned under R¹, in particular methoxy and ethoxy; Alkoxyalkoxy such as methoxyethoxy, ethoxyethoxy, propoxyethoxy, especially methoxyethoxy; cyano; trimethylsilyl; Alkylthio as mentioned under R¹, in particular methylthio and ethylthio; Alkylamino such as methylamino, ethylamino, propylamino; 1-methylethylamino, especially methylamino and ethylamino; Dialkylamino such as dimethylamino, diethylamino, dipropylamino, di (1-methylethyl) amino, methylethylamino, especially dimethylamino and methylethylamino; Cycloalkylamino or dicycloalkylamino, in particular cyclopropylamino and dicyclopropylamino; Alkylsulfinyl such as methylsulfinyl, ethylsulfinyl, propylsulfinyl, 1-methylethylsulfinyl, especially methylsulfinyl and ethylsulfinyl; Alkylsulfonyl such as methylsulfonyl, ethylsulfonyl, propylsulfonyl, 1-methylethylsulfinyl, especially methylsulfonyl and ethylsulfonyl; carboxyl; Alkoxycarbonyl as mentioned under R¹, in particular methoxycarbonyl; Dialkylaminocarbonyl such as dimethylaminocarbonyl, diethylaminocarbonyl, dipropylaminocarbonyl, di- (1-methylethyl) aminocarbonyl, methylethylaminocarbonyl, especially dimethylaminocarbonyl and diethylaminocarbonyl; Dialkoxyphosphonyl such as dimethoxyphosphonyl, diethoxyphosphonyl, dipropoxyphosphonyl, diisopropoxyphosphonyl, especially dimethoxyphosphonyl and diethoxyphosphonyl; Alkaniminoxy such as 2-propaniminoxy; Thienyl, furanyl, tetrahydrofuranyl, N-phthalimido, pyridyl, benzyloxy or benzoyl, where these cyclic radicals may carry one to three of the following groups: halogen, in particular fluorine and chlorine; Alkoxy, in particular methoxy and ethoxy or alkyl, in particular methyl and ethyl;
Benzyl which may carry one to three of the following groups: nitro; cyano; Halogen, in particular fluorine and chlorine; Alkyl as mentioned under R¹, in particular methyl and ethyl; Alkoxy as mentioned under R¹, in particular methoxy and ethoxy; or haloalkyl as generally and in particular mentioned under R¹;
Cycloalkyl as mentioned under R¹, in particular cyclopentyl and cyclohexyl;
Phenyl which may carry one to three of the following groups: alkyl as mentioned under R¹, in particular methyl and ethyl; Alkoxy as mentioned under R¹, in particular methoxy and ethoxy; Haloalkyl as mentioned under R¹, in particular trifluoromethyl; Haloalkoxy as mentioned under R¹, in particular trifluoromethoxy; Alkoxycarbonyl as mentioned above, in particular methoxycarbonyl; Halogen as mentioned under R¹, in particular fluorine, chlorine and bromine; Nitro and cyano;
C₃-C₆ alkenyl, as mentioned under R¹, in particular 2-propenyl and 2-butenyl; C₅-C₆cycloalkenyl such as 2-cyclopentenyl and 2-cyclohexenyl, especially 2-cyclolhexenyl; C₃-C₆-alkynyl as mentioned under R¹, in particular 2-propynyl, wherein the last three groups can carry one of the following radicals: Hyroxy; Alkoxy as mentioned under R¹, in particular methoxy and ethoxy; Halogen as mentioned under R¹, in particular iodine, or phenyl, which in turn may carry one to three of the following groups: alkyl as mentioned under R¹, in particular methyl and ethyl; Alkoxy as mentioned under R¹, in particular methoxy and ethoxy; Haloalkyl as mentioned under R¹, in particular trifluoromethyl; Halogen as mentioned under R¹, in particular fluorine and chlorine; Nitro or cyano;
a five- to six-membered heterocyclic radical having one or two heteroatoms selected from the group oxygen, sulfur and nitrogen as mentioned under R¹, in particular tetrahydrofuranyl and tetrahydropyranyl, or a Benzotriazolrest;
N-phthalimido; tetrahydrophthalimido; succinimido; maleimido;
one equivalent of a cation from the group of alkali or alkaline earth metals, manganese, copper, iron, ammonium and substituted ammonium or
a residue -N = CR⁸R⁹;
R⁸, R⁹ hydrogen; Alkyl as mentioned under R¹, in particular methyl, ethyl and iso-propyl;
Cycloalkyl as mentioned under R¹, in particular cyclopropyl;
phenyl; furyl
or together a methylene chain with 4 to 7 members;
R⁶ hydrogen; C₁-C₆-alkyl as mentioned under R¹, in particular methyl, ethyl, or C₃-C₈-cycloalkyl as mentioned under R¹, in particular cyclopropyl, and
R⁷ hydrogen; C₁-C₆-alkyl as mentioned under R¹, in particular methyl, ethyl, propyl, 1-methylethyl and 1,1-dimethylethyl, stand or
R⁶ and R⁷ together form a methylene chain with 4 or 5 members;
R3 is hydrogen;
C₁-C₆-alkyl as mentioned under R¹, in particular methyl, ethyl, 1-methylethyl, which may carry one to three of the following substituents: hydroxy; Halogen as mentioned under R¹, in particular fluorine and chlorine; Alkoxy as mentioned under R¹, in particular methoxy and ethoxy; Alkylthio as mentioned under R¹, in particular methylthio and ethylthio; or dialkylamino as mentioned under R⁵, in particular dimethylamino;
C₃-C₈cycloalkyl as mentioned under R¹, in particular cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl, which is up to three times by alkyl as mentioned under R¹, in particular methyl, ethyl and 1-methylethyl, halogen as mentioned under R¹, in particular fluorine and chlorine, and haloalkyl as mentioned under R¹, in particular trifluoromethyl may be substituted and
R⁴ hydrogen; hydroxyl; C₁-C₄-alkoxy as mentioned under R¹, in particular methoxy and ethoxy;
C₁-C₆-alkyl as mentioned under R¹, in particular methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl and 1,1-dimethylethyl, which may carry one to three of the following groups: alkoxy as under Called R¹, in particular methoxy and ethoxy; Haloalkoxy as mentioned under R¹, in particular trifluoromethoxy; Alkylthio as mentioned under R¹, in particular methylthio and ethylthio; Halogenalkylthio as mentioned under R¹, in particular trifluoromethylthio; Dialkylamino as mentioned under R⁵, in particular dimethylamino and diethylamino; Halogen as mentioned under R¹, in particular fluorine and chlorine; Cycloalkyl as mentioned for R¹, in particular cyclopropyl, cyclopentyl and cyclohexyl, or phenyl may be substituted, wherein the phenyl radical in turn may carry one to three of the following groups: halogen; cyano; nitro; Alkyl as mentioned under R¹, in particular methyl and ethyl; Haloalkyl as mentioned under R¹, in particular trifluoromethyl; Alkoxy as mentioned under R¹, in particular methoxy and ethoxy; Haloalkoxy as mentioned under R¹, in particular trifluoromethoxy, alkylthio as mentioned under R¹, in particular methylthio and ethylthio; or haloalkylthio as mentioned under R¹, in particular trifluoromethylthio;
C₃-C₈-cycloalkyl as mentioned under R¹, in particular cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl; which may carry one to three of the following groups: alkyl as mentioned under R¹, in particular methyl, ethyl and 1-methylethyl; Haloalkyl as mentioned under R¹, in particular trifluoromethyl; Alkoxy as mentioned under R¹, in particular methoxy and ethoxy; Haloalkoxy as mentioned under R¹, in particular trifluoromethoxy; Halogen as mentioned under R¹, in particular fluorine and chlorine; Nitro or cyano;
C₃-C₆-alkenyl as mentioned under R¹, in particular 2-propenyl and 2-butenyl, which may be substituted one to three times by halogen as mentioned under R¹, in particular fluorine and chlorine, and / or once by phenyl, wherein the phenyl radical in turn may carry one to three of the following groups: alkyl as mentioned under R¹, in particular methyl and ethyl; Haloalkyl as mentioned under R¹, in particular trifluoromethyl; Alkoxy as mentioned under R¹, in particular methoxy and ethoxy; Haloalkoxy as mentioned under R¹, in particular trifluoromethoxy; Alkylthio as mentioned under R¹, in particular methylthio and ethylthio; Halogenalkylthio as mentioned under R¹, in particular trifluoromethylthio; Halogen as mentioned under R¹, in particular fluorine and chlorine; Cyano or nitro;
C₃-C₆-alkynyl as mentioned under R¹, in particular 2-propynyl and 1,1-dimethyl-2-propynyl; which is one to three times by halogen as mentioned under R¹, in particular fluorine and chlorine; and / or may be substituted once by phenyl, wherein the phenyl radical in turn may carry one to three of the following groups: alkyl as mentioned under R¹, in particular methyl and ethyl; Haloalkyl as mentioned under R¹, in particular trifluoromethyl; Alkoxy as mentioned under R¹, in particular methoxy and ethoxy; Haloalkoxy as mentioned under R¹, in particular methylthio and ethylthio; Halogenalkylthio as mentioned under R¹, in particular trifluoromethylthio; Halogen as mentioned under R¹, in particular fluorine and chlorine; Cyano or nitro;
C₁-C₄-dialkylamino as mentioned under R¹, in particular dimethylamino and diethylamino;
a 5- to 6-membered heterocyclic radical having one or two heteroatoms selected from the group oxygen, sulfur or nitrogen as mentioned under R¹, which is one to three times by alkyl as mentioned under R¹, in particular methyl, ethyl and 1-methylethyl; or halogen as mentioned under R¹, in particular fluorine and chlorine may be substituted;
Phenyl which may carry one to four of the following groups: alkyl as mentioned under R¹, in particular methyl, ethyl and 1-methylethyl; Haloalkyl as mentioned under R¹, in particular trifluoromethyl; Alkoxy as mentioned under R¹, in particular methoxy and ethoxy; Haloalkoxy as mentioned under R¹, in particular trifluoromethoxy; Alkylthio as mentioned under R¹, in particular methylthio and ethylthio; Halogenalkylthio as mentioned under R¹, in particular trifluoromethylthio; Halogen as mentioned under R¹, in particular fluorine and chlorine; Nitro, cyano, formyl; C₁-C₄ alkanoyl such as acetyl, propionyl, butyryl, especially acetyl; Haloalkanoyl such as trifluoroacetyl, trichloroacetyl, pentafluoropropionyl, especially trifluoroacetyl; or alkoxycarbonyl as mentioned under R¹, in particular methoxycarbonyl;
Naphthyl which may be substituted one to three times by alkyl as mentioned under R¹, in particular methyl and ethyl, or halogen as mentioned under R¹, in particular fluorine and chlorine, or
R³ and R⁴ together form a C₄-C₇-methylene chain which may be interrupted by oxygen, sulfur or N-methyl, such as - (CH₂) ₃-, [CH₂) ₄-, - (CH₂) ₅-, - (CH₂) ₆- , -CH₂-O-CH₂-, -CH₂-CH₂O-O-CH₂-CH₂-, -CH₂-S-CH₂-, -CH₂-CH₂-S-CH₂-CH₂-, CH₂-CH₂-N (CH₃) - CH₂-CH₂-, in particular - (CH₂] ₅- and -CH₂-CH₂-O-CH₂-CH₂- mean;
or a radical of the formula - (CH₂) ₃-CO-,
as well as their environmentally compatible salts.

Compounds Ia, Ib and Ic, due to their substituted in particular are preferred are listed in the following tables.  

Table A

Table B

Table C

The carboxylic acid amides Ia, Ib and Ic or herbicides containing them Means can be used, for example, in the form of directly sprayable solutions, Powders, suspensions, even high-percentage aqueous, oily or other suspensions or dispersions, emulsions, oil dispersions, Pastes, dusts, litter or granules by spraying, Nebulizing, dusting, scattering or pouring are applied. The Application forms depend on the intended use; they should be in in each case as possible the finest distribution of the active compounds according to the invention guarantee.

The compounds Ia, Ib and Ic are generally suitable for the preparation of directly sprayable solutions, emulsions, pastes or oil dispersions. When inert additives come from mineral oil fractions from medium to high Boiling point, such as kerosene or diesel oil, coal tar oils and oils of vegetable or animal origin, aliphatic, cyclic and aromatic Hydrocarbons, eg. Toluene, xylene, paraffin, tetrahydronaphthalene, alkylated naphthalenes or their derivatives, methanol, ethanol, Propanol, butanol, cyclohexanol, cyclohexanone, chlorobenzene, isophorone or strong polar solvents, such as N, N-dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone or water into consideration.

Aqueous application forms can be prepared from emulsion concentrates, dispersions, Pastes, wettable powders or water-dispersible granules by addition to be prepared from water. For the preparation of emulsions, pastes or oil dispersions may be the substrates as such or in an oil or Solvent dissolved by means of wetting, adhesion, dispersing or emulsifying agent be homogenized in water. It can also be more effective Substance, wetting, adhesion, dispersing or emulsifying agent and possibly solvent or oil existing concentrates are produced to Dilution with water are suitable.

As surface-active substances are the alkali, alkaline earth, ammonium salts of aromatic sulfonic acids, e.g. As lignin, phenol, naphthalene and Dibutylnaphthalenesulfonic acid, as well as fatty acid, alkyl and alkylaryl sulfonates, Alkyl, lauryl ether and fatty alcohol sulfates, as well as salts sulfated hexa-, hepta- and octadecanols, as well as fatty alcohol glycol ethers, Condensation products of sulfonated naphthalene and its Derivatives with formaldehyde, condensation products of naphthalene or the Naphthalenesulfonic acids with phenol and formaldehyde, polyoxyethylene octylphenol ether, ethoxylated isooctyl, octyl or nonylphenol, alkylphenol, Tributylphenyl polyglycol ethers, alkylaryl polyether alcohols, isotridecyl alcohol, Fatty alcohol ethylene oxide condensates, ethoxylated castor oil, Polyoxyethylene alkyl ether or polyoxypropylene, lauryl alcohol polyglycol ether acetate, Sorbitol esters, lignin-sulphite liquors or methylcellulose into consideration.  

• IV. 20 parts by weight of the active ingredient No. 1.005 are in one Mixture dissolved, consisting of 25 parts by weight of cyclohexanone, 65 parts by weight a mineral oil fraction of boiling point 210 to 280 ° C. and 10 parts by weight of the adduct of 40 moles of ethylene oxide to 1 mole of castor oil. By pouring and fine Distributing the solution in 100 000 parts by weight of water is obtained an aqueous dispersion containing 0.02% by weight of the active ingredient.
• V. 20 parts by weight of the active ingredient no. 1,019 are with 3 parts by weight the sodium salt of diisobutylnaphthalene-α-sulfonic acid, 17 parts by weight of the sodium salt of a lignosulfonic acid a sulfite waste liquor and 60 parts by weight of powdered silica gel mixed well and ground in a hammer mill. By finely distributing the mixture in 20,000 parts by weight of water To obtain a spray mixture containing 0.1 wt .-% of the active ingredient contains.
• VI. 3 parts by weight of the active ingredient No. 1,002 are with 97 parts by weight finely divided kaolin mixed. You get that way a dust containing 3% by weight of the active ingredient.
• VII. 30 parts by weight of the active ingredient No. 1.018 are with a Mixture of 92 parts by weight of powdered silica gel and 8 parts by weight of paraffin oil, which is on the surface of this silica gel was sprayed, intimately mixed. You get on this Make a preparation of the drug with good adhesion.
• VIII. 20 parts by weight of the active ingredient No. 1.006 are with 2 parts by weight Calcium salt of dodecylbenzenesulfonic acid, 8 parts by weight Fatty alcohol polyglycol ether, 2 parts by weight of sodium salt of a Phenol-urea-formaldehyde condensates and 68 parts by weight a paraffinic mineral oil intimately mixed. You get one stable oily dispersion.

The application of the herbicidal compositions or of the active ingredients can be carried out in the pre-emergence phase. or post-emergence. Are the active ingredients for certain Crop plants less compatible, so may application techniques be applied, in which the herbicidal agents using the sprayers be sprayed so that the leaves of sensitive crops if possible, are not taken while the active ingredients on the leaves of such growing unwanted plants or the uncovered Floor area (post-directed, lay-by).  

The application rates of active ingredient are depending on the target, season, Target plants and growth stage 0.001 to 5.0, preferably 0.01 up to 3.0 kg / ha of active substance (see above).

In view of the versatility of the application methods, the Compounds according to the invention or agents containing them in one large number of crops to eliminate unwanted plants be used.

To broaden the spectrum of action and to achieve synergistic Effects can the carboxylic acid amides Ia, Ib and Ic with numerous representatives other herbicidal or growth-regulating active ingredient groups mixed and applied together. Example references come as Mixing partners diazines, 4H-3,1-benzoxazine derivatives, benzothiadizinones, 2,6-dinitroanilines, N-phenylcarbamates, thiolcarbamates, halocarboxylic acids, Triazines, amides, ureas, diphenyl ethers, triazinones, uracils, Benzofuran derivatives, cyclohexane-1,3-dione derivatives, quinolinecarboxylic acid derivatives, Aryloxy, heteroaryloxyphenoxypropionic acids and their salts, Esters and amides and others.

In addition, it may be useful to use the compounds Ia, Ib and Ic alone or in combination with other herbicides also with others Mixed pesticides apply together, for example, with Agents for combating pests or phytopathogenic fungi or Bacteria. Also of interest is the miscibility with mineral salt solutions, which used for the elimination of nutritional and trace element deficiencies become. It may also contain non-phytotoxic oils and oil concentrates be added.

synthesis Examples

The instructions given in the Synthesis Examples below were obtained with appropriate modification of the starting compounds for recovery further compounds Ia, Ib and Ic used. The thus obtained Connections are given in the tables below with physical data listed.  

A. Preparation examples for the synthesis of the precursors of the formula IVa example A.1 4-ethoxycarbonyl-5-methyl-isoxazol-3-carbonsäuremethylester

To 9.9 g (0.33 mol) of NaH (80% suspension in white oil) in 1 L of dry Toluene was added dropwise at room temperature 39.0 g (0.3 mol) of ethyl acetoacetate in 100 ml of toluene and stirred for 3 h. Subsequently, one gave 41.3 g (0.3 mol) of methyl α-chloro-α-oximinoacetate in 100 ml of toluene and stirred 12 h at room temperature. Thereafter, the reaction mixture was transferred to a Soxhlet apparatus (extraction sleeve filled with molecular sieve 4 Å), 1 g of methanesulfonic acid was added and heated under reflux for 1.5 h. you allowed to cool, the organic phase washed once each with 200 ml of disodium hydrogen phosphate solution and 200 ml of saturated sodium chloride solution, dried over magnesium sulfate and stripped of the solvent in vacuo. you received 40.4 g (63%) of 4-ethoxycarbonyl-5-methyl-isoxazole-3-carboxylic acid methyl ester as a yellow oil. 1 H-NMR (250 MHz, CDCl₃): δ = 1.34 (t; 3 H), 2.73 (s, 3H), 4.00 (s, 3H), 4.32 (q, 2H).

In an analogous manner, for example, the Isoxazoldicarbonsäurediester IV and IVa are synthesized.

B. Preparation Examples for the Synthesis of Precursors V ' example 8.1 4-ethoxycarbonyl-5-methyl-isoxazole-3-carboxylic acid

To 25.0 g (0.117 mol) of 4-ethoxycarbonyl-5-methyl-isoxazole-3-carboxylic acid methyl ester in 200 ml of dry tetrahydrofuran was added dropwise N₂-atmosphere at -15 to -10 ° C 4.7 g (0.117 mol) of sodium hydroxide in 80 ml Water and stirred for 12 h. The solvents were removed on a rotary evaporator (Bath temperature 30-35 ° C), the residue was taken up in 250 ml of water, adjusted to pH = 8-9 with hydrochloric acid and extracted twice with each 150 ml of diethyl ether. The aqueous phase was then acidified with 6 N HCl to pH = 2 and extracted four times with 250 ml of ethyl acetate. The United organic phases were dried over magnesium sulfate and the Solvent removed in vacuo. 16.2 g (70%) of 4-ethoxycarbonyl-5 methyl-isoxazole-3-carboxylic acid. 1 H-NMR (250 MHz, CDCl₃): δ = 1.42 (t; 3 H), 2.80 (s, 3H), 4.59 (q, 2H).

In an analogous manner, for example, the isoxazole-3-carboxylic acids V ' be synthesized.

C. Preparation Examples for the Synthesis of Precursors VIIa example C.1 5-n-propyl-isoxazole-3-carboxylic acid tert-butylamide

To 10.0 mg (57.6 mmol) of 5-n-propyl-isoxazole-3-carboxylic acid chloride in 250 ml dry dichloromethane, was added dropwise at 5 ° C 9.3 g (128.8 mmol) tert. Butylamine in 20 ml of dichloromethane. The mixture was stirred for 12 h at room temperature, gave 200 ml of water, separated the phases, washed the organic phase once each with 150 ml of saturated sodium bicarbonate solution and 150 ml of saturated Sodium chloride solution, dried over magnesium sulphate and pulled this Solvent in a vacuum. 11.5 g (95%) of 5-n-propylisoxazole-3 were obtained. carboxylic acid tert-butylamide as a solid of mp. 34-37 ° C.

In an analogous manner, for example, the isoxazole-3-carboxamides VIIa be synthesized.  

D. Preparation Examples for the Synthesis of the Precursors of the Formula Vd Example D.1 3-methyl-isothiazole-4-carboxylic acid cyclopropylamide

To 7.2 g (50.0 mmol) of 3-methyl-isothiazole-4-carboxylic acid in 200 ml of dichloromethane 3.7 g (65.0 mmol) of cyclopropylamine were added dropwise in succession at -5 ° C., 18.7 g (185.0 mmol) of methylmorpholine, 2.0 g (16.7 mmol) of dimethylaminopyridine and 43.5 g of a 50% solution of propanephosphonic anhydride in dichloromethane (= 68.4 mmol) and stirred for 12 h at room temperature.  

The solvent was removed in vacuo and the residue was taken up in 250 ml of ethyl acetate and extracted twice with saturated sodium bicarbonate solution and once each with 5% citric acid solution, saturated sodium carbonate solution and saturated sodium chloride solution. The organic phase was dried over magnesium sulfate and the solvent was removed in vacuo. This gave 7.6 g (84%) of 3-methylisothiazole-4-carboxylic acid cyclopropylamide as a solid of mp. 106-108 ° C.

In an analogous manner, for example, the isothiazole-4-carboxylic acid amides Vd be synthesized.

E. Preparation Examples for the Synthesis of Precursors XIII Example E.1 5-piperidinocarbonyl-3-methyl-isoxazol-4-carbonsäuremethylester

To 5.0 g (27.0 mmol) of 4-methoxycarbonyl-3-methyl-isoxazole-5-carboxylic acid in 100 ml of dichloromethane were added dropwise at -5 ° C. in succession to 3.0 g (35.1 mmol) Piperidine, 10.1 g (100.0 mmol) of methylmoprpholine, 1.1 g (9 mmol) of dimethylaminopyridine and 22.9 g of a 50% solution of propanephosphonic anhydride in dichloromethane (36.0 mmol) and stirred at room temperature for 12 h. The solvent was removed in vacuo and the residue was taken up in 200 ml of ethyl acetate and extracted twice with saturated sodium bicarbonate solution and once each with 5% citric acid solution and saturated sodium chloride solution. The organic phase was dried over magnesium sulfate  and the solvent removed in vacuo. 6.1 g (90%) were obtained 5-piperidinocarbonyl-3-methyl-isoxazol-4-carbonsäuremethylester. H-NMR (250 MHZ, CDCl₃): δ = 1.65 (m, 6H), 2.49 (s, 3H), 3.18 (m, 2H), 3.73 (m; 2H), 3.87 (s; 3H).

Example E.2 5-piperidinocarbonyl-3-methyl-isoxazole-4-carboxylic acid

To a solution of 5.7 g (22.6 mmol) of 5-piperidinocarbonyl-3-methylisoxazole 4-carboxylic acid methyl ester in 20 ml of methanol was added dropwise under N₂ at -15 to -10 ° C within 4 h 1.0 g (25.0 mmol) of sodium hydroxide in 20 ml of water and stirred for 12 h at room temperature. You narrowed the solution, The residue was taken up in 100 ml of water, adjusted to pH 8-9 and once extracted with 100 ml of diethyl ether. Then you acidified with 6N HCl to pH 2 and extracted four times with 100 ml dichloromethane. The combined organic phases were dried over magnesium sulfate and the solvent removed in vacuo. 4.9 g (91%) of 5-piperidinocarbonyl 3-methyl-isoxazole-4-carboxylic acid as a solid of mp. 128-130 ° C.

Preparation Examples for the Synthesis of Active Ingredients Ia, Ib and Ic Example 1 3-tert-butylaminocarbonyl-5-n-propyl-isoxazole-4-carboxylic acid

To a solution of 10.0 g (47.6 mmol) of 5-n-propyl-isoxazole-3-carboxylic acid tert-butylamide in 250 ml of dry tetrahydrofuran was added dropwise Nitrogen atmosphere at -70 ° C 104.6 mmol n-butyllithium (67.7 ml of a 1.5 molar solution in hexane) and stirred for 30 min at this temperature. Then poured the reaction mixture to 500 g of solid CO₂ and left stand overnight. It was concentrated, the residue was taken up in 300 ml of water and 20 ml of 2N NaOH, extracted twice with 100 ml of diethyl ether, acidified the aqueous phase with 6N hydrochloric acid to pH 2 and extracted four times with 200 ml of ethyl acetate each time. It was dried over magnesium sulfate and pulled Solvent in a vacuum. This gave 9.7 g (80%) of 3-tert-butylaminocarbonyl 5-n-propyl-isoxazole-4-carboxylic acid. 1 H-NMR (250 MHz, CDCl 3: δ = 1.00 (t, 3H), 1.52 (s, 9H), 1.80 (q, 2H), 3.25 (t, 3H), 7.17 (bs; 1H, NH) (Compound No. 1,013).  

example 2 3-tert-butylaminocarbonyl-5-n-propyl-isoxazole-4-carboxylic acid acetono-ximester

To a solution of 3.3 g (13.0 mmol) of 3-tert-butylaminocarbonyl-5-n- propyl-isoxazole-4-carboxylic acid and 1.2 g (16.9 mmol) of acetone oxime in 100 ml Dichloromethane was added dropwise at room temperature 4.9 g (48.1 mmol) of 4-methylmorpholine and 1.6 g (13.0 mmol) of 4-dimethylaminopyridine and stirred for 5 min. Subsequently, 11.3 g of a 50% solution of propanephosphonic anhydride were added in dichloromethane (= 17.8 mmol) and heated for 12 h Reflux. The mixture was concentrated and the residue was taken up in 100 ml of ethyl acetate, extracted twice with saturated sodium bicarbonate solution as well as each once with 5% citric acid solution, saturated sodium carbonate solution and saturated sodium chloride solution. The organic phase was over Dried magnesium sulfate and the solvent evaporated in vacuo. you obtained 3.8 g (95%) of 3-tert-butylaminocarbonyl-5-n-propyl-isoxazole-4 carboxylic acid acetone oxime ester, mp. 95-96 ° C (compound no. 1014).

example 3 3-tert-butylaminocarbonyl-5-phenyl-isothiazole-4-carboxylic acid

To 2.0 g (8.7 mmol) of 5-phenyl-isothiazole-3,4-dicarboxylic anhydride in 10 ml Dichloromethane was added dropwise with ice-cooling 0.64 g (8.8 mmol) of tert-butylamine and stirred for 3 h at room temperature. Then you narrowed down the solution, added 25 mL of water, acidified to pH 2 with 6N HCl, and extracted three times with 30 ml of ethyl acetate. The organic phase was washed with 20 ml washed saturated sodium chloride solution, dried over magnesium sulfate and concentrated. The residue was chromatographed on silica gel (solvent: Ethanol / toluene 2: 3). 1.3 g (49%) of 3-tert. Butylaminocarbonyl-5-phenylisothiazole-4-carboxylic acid from Zers. 190 ° C (Compound No. 2001).

example 4 5-piperidinocarbonyl-3-methyl-isoxazole-4-carboxylic acid tert-butylamid-

To 4.6 g (19.3 mmol) of 5-piperidinocarbonyl-3-methyl-isoxazole-4-carboxylic acid in 100 ml of dichloromethane was added dropwise at -5 ° C successively 1.8 g (25.1 mmol) t-butylamine, 7.2 g (71.6 mmol) methylmorpholine, 0.8 g (6.4 mmol dimethylaminopyridine and 16.8 g of a 50% solution of Propanephosphonic anhydride in dichloromethane (= 26.4 mmol) and stirred for 12 h  at room temperature. The solvent was removed in vacuo and the residue was removed in 200 ml of ethyl acetate and extracted twice with saturated sodium bicarbonate solution and once each with 5% citric acid solution, saturated sodium carbonate solution and saturated sodium chloride solution. The organic phase was dried over magnesium sulfate and the solvent deducted in vacuo. 5.1 g (90%) of 5-piperidinocarbonyl-3 were obtained. Methyl-isoxazole-4-carboxylic acid tert-butylamide as a solid from M.p. 74-75 ° C (Compound No. 5001).

example 5 4-tert-butylaminocarbonyl-3-methyl-isoxazol-5-carboxylic acid

To 3.3 g (11.3 mmol) of 5-piperidinocarbonyl-3-methyl-isoxazole-4-carboxylic acid tert-butylamide in 150 ml of diethyl ether and 0.4 g (22.2 mmol) of water 7.6 g (67.8 mmol) of potassium tert-butoxide were added in portions and the mixture was stirred for 6 h at room temperature. Then added to 50 ml of water, separated the Phases, the aqueous phase was acidified to pH 2 with 6N HCl and extracted four times with 100 ml of ethyl acetate. The combined organic phases were dried over magnesium sulfate and the solvent in vacuo deducted. After crystallization from cyclohexane / ethyl acetate 5: 1 2.1 g (42%) of 4-tert-butylaminocarbonyl-3-methylisoxazole-5 carboxylic acid as colorless crystals, mp. 142-147 ° C (Compound No. 3001).

example 6 4-Cyclopropylamino-3-methyl-isothiazole-5-carboxylic acid

To a solution of 5.2 g (28.6 mmol) of 3-methylisothiazole-tert-butylamide in 250 ml of tetrahydrofuran was added dropwise under nitrogen atmosphere at -70 ° C. 60.0 mmol of n-butyllithium (40.0 ml of a 1.5 molar solution in hexane) and stirred for 30 min at this temperature. Subsequently, the reaction mixture was poured to 500 g of solid CO₂ and allowed to stand overnight. One narrowed, The residue was taken up in 300 ml of water and 15 ml of 2N NaOH, extracted twice with 100 ml of diethyl ether, the aqueous phase acidified with 6N Hydrochloric acid to pH 2 and extracted four times with 200 ml of ethyl acetate. It was dried over magnesium sulfate and the solvent was removed in vacuo. you received 4.8 g (74%) of 4-cyclopropylamino-3-methyl-isothiazole-5-carboxylic acid as a solid of mp. 131 ° C (Compound No. 4002).  

example 7 4-ethyloxy-carbonyl-5-methyl-isoxazole-3-carboxylic acid tert-butylamide

To 10.6 g (53.3 mmol) of 4-ethoxycarbonyl-5-methyl-isoxazole-3-carboxylic acid in 150 ml of toluene and 2 ml of dimethylformamide were added dropwise at room temperature 12.7 g (106.8 mmol) of thionyl chloride and stirred for 1 h at 80 ° C. They pulled the Solvents in vacuo, the residue dissolved in 200 ml of dry dichloromethane and 10.0 g (137.0 mmol) of tert-butylamine in 20 ml of dry Dichloromethane too. The mixture was stirred for 12 h at room temperature, gave 200 ml of water To separate the phases, the organic phase was washed 4 times 04114 00070 552 001000280000000200012000285910400300040 0002003931627 00004 03995 once each with 150 ml saturated sodium bicarbonate solution and 150 ml saturated sodium chloride solution, dried over magnesium sulphate and drew the solvent in the Vacuum off. 9.8 g (73%) of 4-ethoxycarbonyl-5-methylisoxazole-3 were obtained. carboxylic acid tert-butylamide. 1 H-NMR (250 MHz, CDCl₃): δ = 1.40 (t, 3H), 1.48 (s, 9H), 2.70 (s, 3H), 4.37 (q, 2H), 7.89 (b, 1H, NH) (Compound No. 1036).

example 8 3-tert-butylaminocarbonyl-5-methyl-isoxazole-4-carboxylic acid

To a solution of 5.4 g (21.3 mmol) of 4-ethoxycarbonyl-5-methyl-isoxazol-3-carboxylic acid tert-butylamide in 100 ml of ethanol was added dropwise under N₂ at 5-10 ° C 1.0 g (25.0 mmol) of sodium hydroxide in 50 ml of water and stirred for 12 h. The solution was concentrated, the residue was taken up in 150 ml of water, adjusted to pH = 8-9 and extracted twice with 100 ml of diethyl ether. The aqueous phase was then acidified to pH = 2 with 6N HCl and extracted four times with 200 ml of ethyl acetate each time. The combined organic phases were dried over magnesium sulfate and the solvent was removed in vacuo. This gave 4.6 g (95%) of 3-tert-butylaminocarbonyl-5-methylisoxazol-4-carboxylic acid as a yellow dye of mp. 90-93 ° C (Compound No. 1002).

applications

The herbicidal action of the carboxylic acid amides of the formulas Ia ', Ib' and Ic ' was shown by greenhouse experiments:

The culture containers were plastic flowerpots with loamy sand and about 3.0% humus as substrate. The seeds of the test plants were also species sown separately.

In pre-emergence treatment, those were suspended or emulsified in water Active ingredients directly after sowing by means of finely distributing nozzles applied. The jars were lightly rained to allow germination and growth promote and then covered with transparent plastic hoods, until the plants had grown. This cover causes a uniform Germination of the test plants, if not affected by the active substances has been.

For the post-emergence treatment, the test plants were changed according to Growth form only with a stature height of 3 to 15 cm with the in water treated suspended or emulsified active ingredients. The application rate for postemergence treatment was 1.0 kg / ha a. S.

The plants were species-specific at temperatures of 10-25 ° C or 20-35 ° C held. The trial period lasted for 2 to 4 weeks. During this time, the plants were maintained and their response to the individual treatments were evaluated.

The rating was based on a scale from 0 to 100. 100 means no Rising of the plants or complete destruction of at least the above ground Parts and 0 no damage or normal growth.

The plants used in the greenhouse experiments took off following types together:

Latin name German name Cassia tora - Chenopodium album white goosefoot Chrysanthemum coronarium Crown Wucherblume Ipomoea spp. Morning glory species Polygonum pensylvanicum - Stellaria media Bird chickweed Triticum aestivum winter wheat

With 1.0 kg / ha a. S. used in the post-process, can be with the Examples 1018, 1019, 1002, 1005 and 1006 are broad-leaved undesirable Fight plants very well. Examples 1018, 1019 and 1006 are at the same time compatible in the culture wheat.

Claims (14)

1. Carboxylic acid amides of the formulas Ia, Ib and Ic in which the substituents have the following meaning:
X oxygen or sulfur;
R¹ is hydrogen; Halogen; C₁-C₆-alkyl which may carry one to five halogen atoms and / or one or two of the following radicals: cyclopropyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio or cyano ;
Benzyl which is substituted one to three times by C₁-C₄alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄- haloalkylthio, halogen, cyano or nitro can be;
C₃-C₈-cycloalkyl which may be substituted one to three times by C₁-C₄-alkyl or halogen;
C₂-C₆-alkenyl, which may be substituted one to three times by halogen or C₁-C₃-alkoxy and / or once by phenyl, wherein the phenyl radical in turn may carry one to three of the following groups: C₁-C₄-alkyl, C₁- C₄-haloalkyl, C₁-C₄alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio, halogen, cyano or nitro;
C₂-C₆ alkynyl which may be substituted one to three times by halogen or C₁-C₃ alkoxy and / or once by phenyl, the phenyl radical in turn may carry one to three of the following groups: C₁-C₄-alkyl, C₁- C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio, halogen, cyano or nitro;
C₁-C₄ alkoxy; C₁-C₄-alkylthio; C₁-C₄-haloalkoxy; C₁-C₄ haloalkylthio;
Phenoxy or phenylthio which is one to three times by C₁-C₄alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio, halogen, cyano or Nitro may be substituted;
a 5- to 6-membered saturated or aromatic heterocyclic radical containing one or two heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen which may carry one or two of the following substituents: C₁-C₃alkyl, halogen, C₁-C₃alkoxy and C₁-C₃ alkoxycarbonyl;
Phenyl which may carry one to three of the following groups: C₁-C₆-alkyl, C₁-C₆-haloalkyl, C₁-C₆-alkoxy, C₁-C₆-haloalkyl, C₁-C₆-alkylthio, C₁-C₆-haloalkylthio, halogen, Nitro and cyano;
R² is formyl, 4,5-dihydrooxazol-2-yl, a COYR⁵ radical or a CONR⁶R⁷ radical;
Y oxygen or sulfur;
R⁵ hydrogen; C₁-C₆-alkyl which may carry one to five halogen atoms and / or one of the following radicals: hydroxy, C₁-C₄-alkoxy, C₂-C₄-alkoxy-C₁-C₄-alkoxy, cyano, trimethylsilyl, C₁-C₃-alkylthio , C₁-C₃alkylamino, di-C₁-C₃alkylamino, C₃-C₆cycloalkylamino, di-C₃-C₆cycloalkylamino, C₁-C₃alkylsulfinyl, C₁-C₃alkylsulfonyl, carboxyl, C₁-C₃alkoxycarbonyl, di C₁-C₃-alkylaminocarbonyl, di-C₁-C₃-dialkoxyphosphonyl, C₁-C₃-alkaniminoxy, thienyl, furanyl, tetrahydrofuranyl, N-phthalimido, pyridyl, benzyloxy, benzoyl, said cyclic radicals may carry one to three of the following groups: C₁-C₃alkyl, C₁-C₃alkoxy or halogen;
Benzyl which may carry one to three of the following groups: C₁-C₃ alkyl, C₁-C₃ alkoxy, C₁-C₃ haloalkyl, halogen, nitro and cyano;
C₃-C₈ cycloalkyl;
Phenyl which may carry one to three of the following groups: C₁-C₄ alkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkyl, C₁-C₄ haloalkoxy, C₁-C₄ alkoxycarbonyl, halogen, nitro and cyano;
C₃-C₆-alkenyl, C₅-C₆-cycloalkenyl, C₃-C₆-alkynyl, where these radicals may carry one of the following groups: hydroxy, C₁-C₄-alkoxy, halogen or phenyl, wherein the phenyl radical in turn one to three of the following groups C₁-C₄-alkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkyl, halogen, nitro and cyano;
a five- to six-membered heterocyclic radical having one or two heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen or a benzotriazole radical;
phthalimido; tetrahydrophthalimido; succinimido; maleimido;
one equivalent of a cation from the groups of the alkali or alkaline earth metal, manganese, copper, iron, ammonium and substituted ammonium or a radical -N = CR⁸R⁹;
R⁸, R⁹ is hydrogen, C₁-C₄-alkyl; C₃-C₆ cycloalkyl; Phenyl or furyl,
or together a methylene chain with 4 to 7 members;
R⁶ hydrogen; C₁-C₆-alkyl or C₃-C₈-cycloalkyl and
R⁷ hydrogen; C₁-C₆ alkyl or
R⁶, R⁷ together form a methylene chain with 4 to 5 members;
R3 is hydrogen; C₁-C₆-alkyl which may carry one to three of the following substituents: hydroxy, halogen, C₁-C₄-alkoxy, C₁-C₄-alkylthio or di-C₁-C₄-alkylamino;
C₃-C₈-cycloalkyl which may be substituted one to three times by C₁-C₄-alkyl, halogen and C₁-C₄-haloalkyl;
R⁴ hydrogen; hydroxy; C₁-C₄ alkoxy;
C₁-C₆-alkyl which may carry one to three of the following groups: C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio, di-C₁-C₄-alkylamino, halogen, C₃-C₈-cycloalkyl or phenyl, wherein the phenyl ring in turn may carry one to three of the following radicals: halogen, cyano, nitro, C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy C₁-C₄-alkylthio or C₁-C₄-haloalkylthio;
C₃-C₈ cycloalkyl which may carry one to three of the following groups: C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₄ alkoxy, C₁-C₄ haloalkoxy, halogen, nitro or cyano;
C₃-C₆-alkenyl, which may be substituted one to three times by halogen and / or once by phenyl, wherein the phenyl radical in turn may carry one to three of the following groups: C₁-C₄alkyl, C₁-C₄-haloalkyl, C₁- C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio, halogen, cyano or nitro;
C₃-C₆-alkynyl, which may be substituted one to three times by halogen and / or once by phenyl, where the phenyl radical in turn may carry one to three of the following groups: C₁-C₄alkyl, C₁-C₄-haloalkyl, C₁- C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio, halogen, cyano or nitro, may be substituted;
Di-C₁-C₄-alkylamino;
a 5- to 6-membered heterocyclic saturated or aromatic radical having one or two heteroatoms selected from the group consisting of oxygen, sulfur or nitrogen, which may be substituted one to three times by C₁-C₄-alkyl or halogen;
Phenyl which may carry one to four of the following groups: C₁-C₄-alkyl, C₁-C₄-haloalkyl, C₁-C₄-alkoxy, C₁-C₄-haloalkoxy, C₁-C₄-alkylthio, C₁-C₄-haloalkylthio, halogen, Nitro, cyano, formyl, C₁-C₄-alkanoyl, C₁-C₄-haloalkanoyl or C₁-C₄-alkoxycarbonyl;
Naphthyl, which may be substituted one to three times by C₁-C₄-alkyl or halogen,
or
R³, R⁴ together form a C₄-C₇-methylene chain which may be interrupted by oxygen, sulfur or N-methyl or the radical - (CH₂) ₃-CO-,
where R³ and R⁴ are not simultaneously hydrogen, when

• R¹ is hydrogen, methyl or phenyl and R² is CONH₂, CO₂H or CO₂CH₃ or when
• X is oxygen, R¹ is CH (OCH₂CH₃) ₂ and R² is CONH₂,

as well as their environmentally compatible salts. 2. Carbonsäureamide of the formulas Ia, Ib, Ic according to claim 1, in which R³ Hydrogen means. 3. Carboxylic acid amides of the formulas Ia, Ib, Ic according to claim 1, in which
- R¹ is hydrogen or C₁-C₄-alkyl;
R² COYR⁵, where Y is oxygen and R⁵ is hydrogen or the radical -N = CR⁸R⁹, where
R⁸, R⁹ independently represent hydrogen, C₁-C₄-alkyl and C₃-C₆-cycloalkyl or together form a C₄-C₇-alkylene chain;
R³ is hydrogen and
R⁴ is C₁-C₄-alkyl or C₃-C₈-cycloalkyl
mean. 4. A process for preparing the compounds Ia and Ib according to claim 1, in which R² is CO₂CH₃ and X is oxygen, characterized in that a hydroxamic acid of the formula II in a conventional manner with a β-ketoester of the formula III reacts, the thus obtained dimethyl ester IV then first with one equivalent of an aqueous base to the monoesters Va and Vb hydrolyzed and Va and Vb are then transferred separately or in a mixture first in a manner known per se into the halides or other activated forms of the carboxylic acids and these derivatives are then reacted with a substituted amine of the formula VI amidated. 5. A process for preparing the compounds Ia according to claim 1, in which R² CO₂R⁵, X is oxygen and R⁵ is not hydrogen or methyl, characterized in that a hydroxyamino acid of the formula II according to claim 4 in a conventional manner with a β-keto ester of formula IIIa converts, thus obtained diester IVa subsequently with a saponification reagent to the monoester V ' hydrolyzed and activated and amidated according to claim 4. 6. A process for the preparation of the compounds Ia and Ic according to claim 1, in which R¹ is not hydrogen and R² is carboxyl or formyl and R³ is hydrogen, characterized in that a carboxylic acid Vc or Vd Activated and amidated according to claim 4 and the resulting amide VIIa or VIIb subsequently reacted in a manner known per se in the presence of a base with a carboxylating or a formylating reagent. 7. A process for the preparation of the compounds Ia and Ib according to claim 1, in which R² is a carboxyl group and X is sulfur, characterized in that an isothiazoledicarboxylic anhydride VIII in a manner known per se with an amine of formula VI according to claim 4 to the isomers Ia and Ib and then separates the isomers. 8. A process for the preparation of the compounds Ia, Ib and Ic according to Claim 1, in which R² is CO₂H, characterized in that a corresponding ester Ia, Ib or Ic in which R² is CO₂R⁵ and R⁵ C₁-C₄-alkyl, in a conventional manner in the presence of a hydrolyzed aqueous base. 9. A process for the preparation of the compounds Ia, Ib and Ic according to Claim 1, in which R² denotes a group COYR⁵ or CONR⁶R⁷, characterized in that a corresponding carboxylic acid Ia, Ib or Ic (R² = CO₂H) activated according to claim 4 and then in known manner with a compound IX HYR⁵ (IX) or derivatized with an amine VI according to claim 4. 10. A process for preparing the compounds Ia, Ib and Ic according to claim 1, in which R² is 4,5-dihydrooxazol-2-yl, characterized in that a carboxylic acid amide of the formula Ia, Ib or Ic according to claim 1, in which R² is a group CO₂H or CO₂R⁵ and R⁵ C₁-C₄-alkyl, in a conventional manner with an aminoalcohol X. cyclized. 11. A process for the preparation of the compounds Ib according to claim 1, in where R² is formyl, characterized in that a corresponding Carboxylic acid of the formula Ib (R² = CO₂H) according to claim 4 in the Halide or another activated form of the carboxylic acid transferred and this derivative is subsequently reduced in a manner known per se. 12. A herbicidal composition containing a carboxylic acid amide of the formula Ia ', Ib' or Ic ', in which the substituents have the meaning given in claim 1 and R³ and R⁴ can simultaneously be hydrogen, if

• R¹ is hydrogen, methyl or phenyl and R² is CONH₂, CO₂H or CO₂CH₃ or when
• X is oxygen, R¹ is CH (OCH₂CH₃) and R² is CONH₂.

13. A method for controlling undesired plant growth, thereby characterized in that the unwanted plants and / or their Habitat with a herbicidally effective amount of at least one Carbonsäureamids the formula Ia ', Ib' or Ic 'treated.