Isoxazole(isothiazole)-5-carboxamides

The present invention relates to substituted isoxazole- and isothiazole-5-carboxamides and their use for controlling undesirable plant growth.
Isoxazole- and isothiazolecarboxylic acids and their derivatives are known. These are 5-aminocarbonyl-3-methylisoxazole-4-carboxylic acid, ethyl 5-aminocarbonyl-3-methylisoxazole-4-carboxylate, isothiazole-4,5-dicarboxamide and 5-carbamoylisothiazole-4-carboxylic acid (J. Chem. Soc. Perkin Trans. I 1982, 2391; J. Heterocycl. Chem. 22 (1985), 1561 and J. Chem. Soc. 1959, 3961). Possible uses of these substances are not described.
We have found that isoxazole(isothiazole)-5-carboxamides of the formula Ia ##STR2## where X is oxygen or sulfur,
R.sup.1 is hydrogen,
C.sub.1 -C.sub.10 -alkyl which is unsubstituted or substituted by C.sub.1 -C.sub.3 -alkoxy, C.sub.1 -C.sub.3 -haloalkoxy, halogen, cyano or phenyl which may be substituted by halogen, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -haloalkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -haloalkoxy, C.sub.1 -C.sub.4 -alkylthio. C.sub.1 -C.sub.4 -haloalkylthio, cyano or nitro, C.sub.1 -C.sub.4 -alkoxy,
C.sub.3 -C.sub.8 -cycloalkyl which is unsubstituted or substituted by C.sub.1 -C.sub.4 -alkyl or halogen,
a 5-membered or 6-membered heterocyclic radical having one or two heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen, which may be substituted by C.sub.1 -C.sub.4 -alkyl, carboxyl or C.sub.1 -C.sub.4 -alkoxycarbonyl,
or phenyl which is unsubstituted or substituted by C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -haloalkyl, C.sub.1 -C.sub.6 -alkoxy, C.sub.1 -C.sub.6 -haloalkoxy, C.sub.1 -C.sub.6 -alkylthio, C.sub.1 -C.sub.6 -haloalkylthio, halogen, nitro or cyano,
R.sup.2 is formyl, 4,5-dihydrooxazol-2-yl or a radical of the formula COYR.sup.5 or CONR.sup.6 R.sup.7, where
Y is oxygen or sulfur,
R.sup.5 is hydrogen,
C.sub.1 -C.sub.8 -alkyl which may be substituted by C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkoxy-C.sub.1 -C.sub.4 -alkoxy, halogen, cyano, hydroxyl, trimethylsilyl, C.sub.1 -C.sub.4 -alkylthio, C.sub.1 -C.sub.4 -alkylamino, C.sub.1 -C.sub.4 -dialkylamino, C.sub.1 -C.sub.4 -alkylsulfinyl, C.sub.1 -C.sub.4 -alkylsulfonyl, carboxyl, C.sub.1 -C.sub.4 -alkoxycarbonyl, C.sub.1 -C.sub.4 -dialkylaminocarbonyl, C.sub.1 -C.sub.4 -dialkoxyphosphonyl, alkyliminooxy, benzyloxy, benzoyl which is unsubstituted or substituted by C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.3 -alkoxy or halogen, or phenyl which is unsubstituted or substituted by C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -haloalkyl, halogen, nitro or cyano, or may be substituted by thienyl, furyl, tetrahydrofuryl, phthalimido or pyridyl,
C.sub.3 -C.sub.8 -alkenyl which is unsubstituted or substituted by phenyl which may be substituted by C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -haloalkyl, halogen, nitro or cyano, C.sub.3 -C.sub.6 -haloalkenyl,
C.sub.3 -C.sub.8 -alkynyl which is unsubstituted or substituted by hydroxyl or C.sub.1 -C.sub.4 -alkoxy, C.sub.3 -C.sub.6 -cycloalkyl, C.sub.5 - or C.sub.6 -cycloalkenyl,
phenyl which is unsubstituted or substituted by C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -haloalkyl, halogen, nitro, cyano, C.sub.1 -C.sub.4 -alkoxycarbonyl or acylamino,
a 5-membered or 6-membered heterocyclic radical having one or two heteroatoms selected from the group consisting of oxygen, sulfur and nitrogen or a benzotriazole radical,
C.sub.6 - C.sub.7 -cycloalkylimino, phthalimido, succinimido, or a radical ##STR3## --CH.sub.2 --CH(OH)--CH.sub.2 (OH) or one equivalent of a cation from the group consisting of the alkali metals, alkaline earth metals, manganese, copper, iron, ammonium and substituted ammonium, or a radical ##STR4## where R.sup.8 and R.sup.9 independently of one another are each C.sub.1 -C.sub.4 -alkyl, C.sub.2 -C.sub.6 -alkoxyalkyl, C.sub.3 -C.sub.8 -cycloalkyl, phenyl or furyl or together form a methylene chain of the formula --(CH.sub.2).sub.m --, where m is from 4 to 7, and R.sup.9 is additionally hydrogen,
R.sup.6 is hydrogen, C.sub.1 -C.sub.8 -alkyl or C.sub.3 -C.sub.8 -cycloalkyl and R.sup.7 is hydrogen or C.sub.1 -C.sub.8 -alkyl, or
R.sup.6 and R.sup.7 form a methylene chain having 4 or 5 members, R.sup.3 is hydrogen,
C.sub.1 -C.sub.6 -alkyl which is unsubstituted or substituted by hydroxyl, halogen, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylthio or C.sub.1 -C.sub.4 -dialkylamino
or C.sub.3 -C.sub.8 -cycloalkyl which is unsubstituted or substituted by C.sub.1 -C.sub.4 -alkyl, halogen or C.sub.1 -C.sub.4 -haloalkyl, and
R.sup.4 is hydrogen, hydroxyl, C.sub.1 -C.sub.4 -Alkoxy, C.sub.1 -C.sub.10 -alkyl which is unsubstituted or substituted by C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -haloalkoxy, C.sub.1 -C.sub.4 -alkylthio, C.sub.1 -C.sub.4 -dialkylamino, halogen, C.sub.3 -C.sub.6 -cycloalkyl or phenyl which may be substituted by halogen, cyano, nitro, C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -haloalkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -haloalkoxy, C.sub.1 -C.sub.4 -alkylthio or C.sub.1 -C.sub.4 -halo-alkylthio, C.sub.3 -C.sub.10 -alkynyl or
C.sub.3 -C.sub.10 -alkenyl which is unsubstituted or substituted by halogen or C.sub.1 -C.sub.4 -alkoxy,
C.sub.3 -C.sub.8 -cycloalkyl which is unsubstituted or substituted by C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -haloalkyl, C.sub.1 -C.sub.6 -alkoxy, C.sub.1 -C.sub.6 -haloalkoxy, C.sub.1 -C.sub.6 -haloalkylthio, halogen, nitro or cyano, C.sub.1 -C.sub.4 -dialkylamino, a 3-membered or 6-membered heterocyclic radical which is unsubstituted or substituted by C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -haloalkyl or halogen and has one or two heteroatoms selected from the group consisting of oxygen, sulfur and unsubstituted or methylsubstituted nitrogen, naphthyl, or phenyl which is unsubstituted or substituted by C.sub.1 -C.sub.6 -alkyl, C.sub.1 -C.sub.6 -haloalkyl, C.sub.1 -C.sub.6 -alkoxy, C.sub.1 -C.sub.6 -haloalkoxy, C.sub.1 -C.sub.6 -alkylthio, C.sub.1 -C.sub.6 -haloalkylthio, halogen, nitro, cyano, formyl, C.sub.1 -C.sub.6 -alkanoyl or C.sub.1 -C.sub.6 -haloalkanoyl, or R.sup.3 and R.sup.4 together form a radical of the structure --(CH.sub.2).sub.n --Y.sub.p --(CH.sub.2).sub.1 --, where n and q are each 1, 2 or 3, p is 0 or 1 and Y is oxygen, sulfur or N-methyl, or the radical of the formula
--(CH.sub.2).sub.3 --CO--
and their agriculturally acceptable salts possess herbicidal activity.
The methyl, alkoxy, alkenyl and alkynyl radicals R.sup.1, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7 may be straight-chain or branched and are preferably of 1 to 4 carbon atoms. The same applies to the alkyl radicals which may be present as substituents in the radicals R.sup.1, R.sup.3, R.sup.4, R.sup.5, R.sup.6 and R.sup.7, and to the alkyl groups in the haloalkyl, alkoxy, haloalkoxy, alkylthio, haloalkylthio, dialkylamino, alkanoyl, haloalkanoyl and alkoxycarbonyl radicals.
Preferred halogen substituents are chlorine substituents.
The heterocyclic radicals R.sup.1 are saturated or unsaturated. Suitable examples are tetrahydropyranyl, tetrahydrofuryl, pyrazolyl, thienyl, furyl, pyridyl and tetrahydrofuryl. These radicals may be substituted by C.sub.1 -C.sub.4 -alkyl, carboxyl or C.sub.1 -C.sub.4 -alkylcarbonyl.
The heterocyclic radicals R.sup.5 may be saturated or unsaturated. Suitable radicals are thienyl, furyl, tetrahydrofuryl, triazolyl, imidazolyl, tetrahydropyranyl, pyridyl, morpholino and piperidino.
Saturated or unsaturated heterocyclic radicals R.sup.4 are, for example, tetrahydropyranyl, tetrahydrofuryl thiazolyl, pyridyl, morpholino, piperidino and pyrimidyl.
The novel compounds I can form addition salts, for example with inorganic and organic acids or with alkyl halides, or, if one of the substituents has acidic properties, they can be reacted with inorganic and organic bases to give salts. The present invention also relates to such salts, to the extent that they are agriculturally acceptable.
Isoxazole(isothiazole)-5-carboxamides which are preferred herbicidal active ingredients are those of the formula Ia, where R.sup.3 is hydrogen.
Other compounds of the formula Ia which are preferred active ingredients ate those in which X is oxygen or sulfur, R.sup.1 is hydrogen or C.sub.1 -C.sub.4 -alkyl, R.sup.2 is COYR.sup.5, R.sup.3 is hydrogen and R.sup.4 is C.sub.1 -C.sub.4 -alkyl or C.sub.3 -C.sub.8 -cycloalkyl. In these compounds, R.sup.5 is preferably hydrogen, C.sub.1 -C.sub.4 -alkyl, or phenyl which is unsubstituted or substituted by C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -haloalkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkylthio or halogen, or a radical ##STR5## wherein R.sup.8 and R.sup.9 in turn are preferably each C.sub.1 -C.sub.4 -alkyl.
Isoxazole(isothiazole)-5-carboxamides of the formula ##STR6## where X, R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the meanings stated for formula Ia, with the proviso that X is sulfur when R.sup.1 is CH.sub.3, R.sup.2 is COOH or COOC.sub.2 H.sub.5 and R.sup.3 and R.sup.4 are each hydrogen, and that X is oxygen when R.sup.1 is hydrogen, R.sup.2 is COOH or CONH.sub.2 and R.sup.3 and R.sup.4 are each hydrogen, are novel.
The isoxazole(isothiazole)-5-carboxamides of the formula I or Ia can be prepared by the following methods:
1. A process for the preparation of compounds of the formula Ib and Ia, where R.sup.2 is COOR.sup.5 and R.sup.5 is hydrogen or C.sub.1 -C.sub.8 -alkyl (cf. Scheme 1), is based on the reaction of a dialkyl isoxazole- or isothiazole-4,5-dicarboxylate II (R.sup.8 .dbd.C.sub.1 -C.sub.8 -alkyl) with an aqueous base and subsequent reaction with a mineral acid to give a carboxylic acid III. Particularly suitable dicarboxylates II are lower alkyl esters (R.sup.5 .dbd.R.sup.8 .dbd.C.sub.1 -C.sub.4 -alkyl), dimethyl and diethyl esters being particularly preferred.
The reaction is carried out by treating a dialkyl dicarboxylate II with a strong base for example NaOH, KOH or Ca(OH).sub.2, at from about 0.degree. to 80.degree. C., preferably from 0.degree. to 50.degree. C., in an organic solvent, e.g. methanol or ethanol. In general, about one equivalent of the strong base is used in aqueous solution. When the reaction is complete, the mixture is cooled and acidified with a strong mineral acid, for example hydrochloric acid or sulfuric acid. The resulting carboxylic acid III can be isolated in a conventional manner, for example by filtration under suction or by extraction with an organic solvent.
To convert the carboxylic acid III into the carbonyl halide IV, the acid III is reacted in a conventional manner with an inorganic acid halide, such as thionyl chloride, a phosphorus trihalide or a phosphorus pentahalide, the chlorides being preferred. Advantageously, the inorganic acid halide is used in an amount of from 1 to 5, preferably from 1 to 2, molar equivalents. The reaction can be carried out in the absence of a solvent or in the presence of an inert organic solvent, for example benzene or toluene, at from room temperature to the boiling point of the inorganic acid halide or of the inert organic solvent. In some cases, the addition of a catalyst, such as dimethylformamide or 4-dimethylaminopyridine, may be advantageous. When the reaction is complete, the acyl halide IV can be isolated in a conventional manner, for example by distilling off the excess inorganic acid halide and the organic solvent and then distilling the acyl chloride IV under atmospheric or reduced pressure.
The carboxamides Ib are obtained from the carbonyl halides by reaction with an amine V. For this purpose, it is advantageous if the carbonyl halide, in an inert organic solvent, such as dichloroethane, or an ether, such as diethyl ether or methyl tert-butyl ether, is reacted with an amine V, likewise dissolved in an organic solvent. The amine V is advantageously used in from 2 to 5, preferably from 2 to e, times the molar amount in order to bind the resulting hydrogen halide. The reaction may also be carried out in the presence of an auxiliary base, such as a tertiary amine, e.g., triethylamine. In this case, from 1 to 1.5 molar equivalents of amine V are sufficient. The reaction temperature may be from 0.degree. to 50.degree. C., preferably from 0.degree. to 20.degree. C. The reaction is generally complete after from 1 to 12 hours. The mixture can be worked up in a conventional manner, for example by hydrolysis with water and extraction of the product of the formula Ib with an organic solvent and evaporation of the organic solvent. The product of the formula Ib can be purified, for example, by recrystallization of chromatography.
The 4-alkoxycarbonylisoxazole-5-carboxamides or 4-alkoxycarbonylisothiazole-5-carboxamides Ib can be converted into the free carboxylic acids Ic by reaction with an aqueous base followed by reaction with a mineral acid. the react-tion is carried out by treating the ester Ib, in an or-ganic solvent, e.g. methanol or ethanol, with a base, e.g. NaOH, KOH or Ca(OH).sub.2, at from 0.degree. to 80.degree. C., preferably from 0.degree. to 50.degree. C. In general, about 1-3, preferably 1-1.5, equivalents of the strong base are used in aqueous solu-tion. When the reaction is complete, the mixture is acidified with a strong mineral acid, for example hydro-chloric acid or sulfuric acid, while cooling. The resulting carboxylic acids Ic can be isolated by filtration under suction or by extraction with an organic solvent and evaporation of this organic solvent. The acid Ic may be further purified by recrystallizing or chromatographing them. ##STR7##
The dialkyl isoxazole- and isothiazole-4,5-dicarboxylates II required as starting materials for this process are known from the literature (J. Org. Chem. 43 (1978), 3736; Chem. Parm. Bull. 28 (1980), 3296; Tetrahedron 30 (1974), 1365); those which are unknown can be prepared by methods generally known from the literature.
2. A further process for the preparation of the compounds Id is based on the reaction of an isoxazole- or isothiazole-5-carbonyl halide VI with an amine V. Preferred carbonyl halides VI are the chlorides. In this procedure, it is advantageous to react the carbonyl halide, in an inert organic solvent, such as dichloromethane, or an ether, such as diethyl ether or methyl tert-butyl ether, with an amine V, likewise dissolved in an organic solvent. The amine V is advantageously used in from 2 to 5, preferably from 2 to 3, times the molar amount in order to bind the resulting hydrogen halide. The reaction may also be carried out in the presence of an auxiliary base, for example a tertiary amine (triethylamine). In this case, from 1 to 1.5 molar equivalents of amine V are sufficient. The reaction temperature may be from 0.degree. to 50.degree. C., preferably from 0.degree. to 20.degree. C. The reaction is generally complete after from 1 to 12 hours. The mixture can be worked up in a conventional manner, for example by hydrolysis with water and extraction of the product VII with an organic solvent and evaporation of the organic solvent.
The isoxazole- or isothiazolecarboxamides VII are converted into the 5-aminocarbonylisoxazole-4-carboxylic acids or 5-aminocarbonylisothiazole-4-carboxylic acids of the formula Id by reaction with an alkyllithium, preferably with the addition of a solvent which is inert under the reaction conditions, such as diethyl ether or tetrahydrofuran. As a rule, the reaction is carried out under a nitrogen atmosphere at from -70.degree. to -80.degree. C. In this process, the alkyllithium compound is generally used in from 2 to 3 times the molar amount, based on amide of the formula VII used. When the reaction is complete, the mixture is treated with carbon dioxide, preferably in an inert solvent, such as diethyl ether or, for example, tetrahydrofuran, the desired products of the formula Id, where R.sup.2 is carboxyl, being obtained.
Using the same process, it is also possible to obtain isoxazole- and isothiazolecarboxamides of the formula Id, where R.sup.2 is formyl, if dimethylformamide is used instead of the carbon dioxide. Working up in a conventional manner gives substituted 4-formylisoxazole-5-carboxamides or 4-formylisothiazole-5-carboxamides of the formula Id. ##STR8##
The isoxazole- and isothiazole-5-carbonyl halides VI required as starting materials for this process are known from the literature. Those which are unknown can be prepared from the corresponding carboxylic acids VIII in a conventional manner, as described above. ##STR9##
The carboxylic acids VIII required for this purpose are likewise known to the literature (Chem. Ber. 106 (1973), 3345, J. Chem. Soc. 1959, 3061, J. Chem. Soc. 1963, 2032, Adv. in Hterocyclic Chem. 14 (1972), 1); those which are unknown can be prepared by methods generally known from the literature, for example from the corresponding alcohols or aldehydes by oxidation or from the corresponding nitriles by hydrolysis.
3. Another process lead to compounds Ie, in which R.sup.2 is COOR.sup.5 and R.sup.5 is C.sub.1 -C.sub.6 -alkyl which is unsubstituted or substituted by C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -alkoxy-C.sub.1 -C.sub.4 -alkoxy, halogen, C.sub.1 -C.sub.4 -alkylthio, C.sub.1 -C.sub.4 -alkylsulfinyl, C.sub.1 -C.sub.4 -alkylsulfonyl, C.sub.1 -C.sub.4 -alkoxycarbonyl or benzyloxy or by phenyl which may be substituted by C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -haloalkyl, halogen, nitro or cyano, or R.sup.5 is C.sub.3 -C.sub.6 -cycloalkyl or is C.sub.3 -C.sub.8 -alkenyl which is unsubstituted or substituted by phenyl which may be substituted by C.sub.1 -C.sub.4 -alkyl, C.sub.1 -C.sub.4 -alkoxy, C.sub.1 -C.sub.4 -haloalkyl, halogen, nitro or cyano, or R.sup.5 is C.sub.3 -C.sub.8 -alkynyl, C.sub.6 - or C.sub.7 -cycloalkylimino, succinimido or a radical of the formula ##STR10## by reaction of an acid Ic with a corresponding alcohol IX in the presence of a strong mineral acid, for example hydrochloric acid or sulfuric acid, at from 0.degree. to 100.degree. C., preferably from 20.degree. to 50.degree. C. As a rule, an excess of the alcohol IX is used, but it is also possible to employ an inert solvent. ##STR11## 4. In a further process for the preparation of the compounds of the formula Ie, an acid Ic is reacted with an alcohol or thios IX in the presence of a dehydrating agent (e.g. dicyclohexylcarbodiimide (DCC)) at from -20.degree. to 50.degree. C., preferably from 0.degree. to 30.degree. C. As a rule, the starting materials are used for the reaction in a roughly stoichiometric amount. The reaction is preferably carried out in the presence of an inert solvent, for example tetrahydrofuran, dichloromethane or toluene. ##STR12## 5. Another process for the preparation of the compounds Ic is based on the reaction of the alkyl carboxylate If with an alkali metal alkoxide X, such as sodium alkoxide or potassium alkoxide, with a corresponding alcohol IX in a conventional manner at from 20.degree. C. to the boiling point of the selected alcohol IX. ##STR13## 6. Compounds of the formula Ig, where R.sup.2 is COOR.sup.5 and R.sup.5 is a salt-forming cation, for example an alkali metal, alkaline earth metal, ammonium or substituted ammonium ion, are obtained by reacting a substituted isoxazole- or isothiazole-4-carboxylic acid Ic with one equivalent of the salt-forming cation. If the cation in question is an inorganic cation, for example sodium, potassium or calcium, the acid Ic is advantageously dissolved or suspended in water or in a lower alcohol or a mixture of these, and one equivalent of the salt-forming cation is added. The salt-forming cation may be used, for example, int he form of its hydroxide, carbonate or bicarbonate, preferably in the form of its hydroxide. The reaction is generally complete after a few minutes, and the mixture can be worked up in a conventional manner, for example by precipitation and filtration under suction or by evaporation of the solvent. To prepare compounds Ig in which B.sym. is ammonium or organic ammonium, the acid Ic is dissolved or suspended in an organic solvent, e.g. diethyl ether, tetrahydrofuran or dioxane, and the mixture is treated with one equivalent of ammonia, an amine or a tetraalkylammonium hydroxide.
Among the amines which may e used the following should be mentioned: methylamine, ethylamine, n-propylamine, isopropylamine, n-butylamine, isobutylamine, secbutylamine, n-amylamine, isoamylamine, hexylamine, heptylamine, octylamine, nonylamine, decylamine, undecylamine, dodecylamine, tridecylamine, tetradecylamine, pentadecylamine, hexadecylamine, heptadecylamine, octadecylamine, methylethylamine, methylisopropylamine, methylhexylamine, methylnonylamine, methylpentadecylamine, methyloctadecylamine, ethylbutylamine, ethylheptylamine, ethyloctylamine, hexylheptylamine, hexloctylamine, dimethylamine, diethylamine, di-n-propylamine, diisopropylamine, di-n-amylamine, diisoamylamine, dihexylamine, diheptylamine, dioctylamine, trimethylamine, triethylamine, tri-n-propylamine, triisopropylamine, tri-n-butylamine, triisobutylamine, tri-sec-butylamine, tri-n-amylamine, ethanolamine, n-propanolamine, isopropanolamine, diethyanolamine, N,N-deiethylethanolamine, N-ethylpropanolamine, N-butylethanolamine, allylamine, n-buten-2-ylamine, n-penten-2-ylamine, 2,3-dimethylbuten-2-ylamine, dibuten-2-ylamine, n-hexen-2-ylamine, propylenediamine, tallowamine, cyclopentylamine, cyclohexylamine, dicyclohexylamine, peiperidine, morpholine and pyrrolidine.
In the case of tetraalkylammonium hydroxides, for example, tetramethyl-, tetraethyl- or trimethylbenzylammonium hydroxide may be used. As a rule, the ammonium salt or organic ammonium salt is precipitated from the solution and can be isolated by a conventional method. Alternatively, the salt of the formula Ig can also be obtained by evaporating the solvent. ##STR14## 7. Another process leads to compounds Ih in which R.sup.2 is CONR.sup.6 R.sup.7. It consists in reacting an ester Ib with a primary or secondary amine XI. The process is carried out by reacting an ester Ib with from 1 to 50 times the molar amount of amine XI, in the presence or absence of an organic solvent, at from room temperature to the boiling point of the amine or of the organic solvent. Preferred esters Ib are lower alkyl esters, particularly the methyl and ethyl esters. The reaction products Ih can be isolated in a conventional manner, for example by filtration under suction or evaporation of the solution and, if required, can be further purified by recrystallization or chromatography. ##STR15## 8. In another process for the synthesis of the compounds Ib, a dialkyl isoxazole- or isothiazole-4,5-dicarboxylate II is reacted with an amine V.
Particularly suitable dialkyl esters II are lower alkyl esters, preferably dimethyl esters or diethyl esters. The reaction is carried out by treating a dialkyl dicarboxylate II with about one equivalent of a primary or secondary amine V at from 0.degree. to 100.degree. C., preferably from 50.degree. to 80.degree. C., in an organic solvent, for example an alcohol, such as methanol or ethanol. When the reaction is complete, the mixture is cooled and filtered under suction or evaporated down. The resulting product of the formula Ib can be further purified by a conventional standard method, such as recrystallization or chromatography. ##STR16## 9. Compounds of the formula Ii can be obtained by reacting a substituted isothiazole-4,5-dicarboxylic anhydride XII with an amine V. The reaction is advantageously carried out by initially taking the anhydride XII in an inert solvent, such as an ether or a halohydrocarbon, and adding dropwise about a molar amount of an amine V, if necessary likewise dissolved in an inert solvent. After the reaction is complete the reaction product is filtered off under suction or isolated by evaporating the solvent used. In some cases, the isomeric amides XIII may be formed in this process, the amides Ii generally being the preferred ones. ##STR17##
The isothiazole-4,5-dicarboxylic anhydrides XII required as starting materials for this process are known from the literature (J. Chem. Soc. 1959, 3061); those which are unknown can be synthesized by methods which are generally known from the literature.
10. In another process for the preparation of compounds of the formula Ik, an acid Ic is reacted with an alcohol or thiol XIV in the presence of a 1-methyl-2-halopyridinium iodide at from 20.degree. to 80.degree. C., preferably from 30.degree. to 40.degree. C. The reaction is carried out in the presence of an inert solvent, e.g. dichloromethane or toluene. The process is known in principle from the literature (Chem. Lett. 1045 (1975); ibid. 13 (1976); ibid. 49 (1976)). ##STR18##
The examples which follow illustrate the preparation of the intermediates for the synthesis of the compounds I or Ia.

EXAMPLE A
11.7 g of aniline are added dropwise to 10.0 g of 3-ethylisoxazole-5-carbonyl chloride in 150 ml of dichloromethane, while cooling with ice. The mixture is stirred overnight at room temperature, water and concentrated hydrochloric acid are added and the organic phase is separated off, washed with sodium bicarbonate solution and evaporated down to give 11.8 g of 3-ethylisoxazole-5-carboxanilide as colorless crystals of melting point 122.degree.-124.degree. C.
For example, the isoxazole-5-carboxamides VII can be synthesized in a similar manner:
______________________________________ ##STR19## (VII)R.sup.1 R.sup.4 mp. [.degree.C.]______________________________________H i-C.sub.3 H.sub.7H tert-C.sub.4 H.sub.9 103-106H cyclo-C.sub.3 H.sub.5H cyclo-C.sub.6 H.sub.11H C.sub.6 H.sub.5CH.sub.3 H 167-171CH.sub.3 i-C.sub.3 H.sub.7 92-93CH.sub.3 tert-C.sub.4 H.sub.9 55-60CH.sub.3 1-Ethylcyclohexyl oilCH.sub.3 4-Methyltetrahydro- 63-65 pyran-4-ylCH.sub.3 C.sub.6 H.sub.5 145-147CH.sub.3 4-ClC.sub.6 H.sub.4 216-219CH.sub.3 3-CF.sub.3C.sub.6 H.sub.4 146-148C.sub.2 H.sub.5 i-C.sub.3 H.sub.7 85-87C.sub.2 H.sub.5 tert-C.sub.4 H.sub.9 67-70C.sub.2 H.sub.5 4-ClC.sub.6 H.sub.4 170-173C.sub.2 H.sub.5 3-CF.sub.3C.sub.6 H.sub.4 121-122i-C.sub.3 H.sub.7 Hi-C.sub.3 H.sub.7 CH.sub.3 69-73i-C.sub.3 H.sub.7 C.sub.2 H.sub.5 69-72i-C.sub.3 H.sub.7 n-C.sub.3 H.sub.7 79-80i-C.sub.3 H.sub.7 i-C.sub.3 H.sub.7 122-125i-C.sub.3 H.sub.7 n-C.sub.4 H.sub.9 67-68i-C.sub.3 H.sub.7 sec-C.sub.4 H.sub.9 133-135i-C.sub.3 H.sub.7 i-C.sub.4 H.sub.9 85-86i-C.sub.3 H.sub.7 tert-C.sub.4 H.sub.9 116-118i-C.sub.3 H.sub.7 C(CH.sub.3).sub.2 C.sub.2 H.sub.5 118-120i-C.sub.3 H.sub.7 C(CH.sub.3).sub.2 C.sub.3 H.sub.7 33-34i-C.sub.3 H.sub.7 C(CH.sub.3).sub.2 CH.sub.2 C(CH.sub.3).sub.3 65-66i-C.sub.3 H.sub.7 C(CH.sub.3).sub.2 CH.sub.2 SCH.sub.3 42i-C.sub.3 H.sub.7 CH.sub.2 CH.sub.2 SCH.sub.3i-C.sub.3 H.sub.7 CH.sub.2 CH.sub.2 CH.sub.2 SCH.sub.3 34-36i-C.sub.3 H.sub.7 CH.sub.2 CH.sub.2 OCH.sub.3 oili-C.sub.3 H.sub.7 CH.sub.2 CH.sub.2 N(CH.sub.3).sub.2 oili-C.sub.3 H.sub.7 cyclo-C.sub.3 H.sub.5 88-90i-C.sub.3 H.sub.7 cyclo-C.sub.6 H.sub.11 152-154i-C.sub.3 H.sub.7 1-Methylcyclohexyli-C.sub.3 H.sub.7 1-Ethylcyclohexyl 50-51i-C.sub. 3 H.sub.7 4-Methyltetrahydro- 94-96 pyran-4-yli-C.sub.3 H.sub.7 4-Ethyltetrahydro- 50-51 pyran-4-yli-C.sub.3 H.sub.7 C(CH.sub.3).sub.2 -cycloC.sub.6 H.sub.11 83i-C.sub.3 H.sub.7 CH.sub.2 CHCH.sub.2 65-66i-C.sub.3 H.sub.7 C(CH.sub.3).sub.2 CHCH.sub.2 99-106i-C.sub.3 H.sub.7 C(CH.sub.3).sub.2 CCH 85-86i-C.sub.3 H.sub.7 CH.sub.2C.sub.6 H.sub.5 79-81i-C.sub.3 H.sub.7 C(CH.sub.3).sub.2 C.sub.6 H.sub.5i-C.sub.3 H.sub.7 CH.sub.2C(CH.sub.3).sub.3 87-89i-C.sub.3 H.sub.7 C.sub.6 H.sub.5 106-108i-C.sub.3 H.sub.7 4-ClC.sub.6 H.sub.4 176-178i-C.sub.3 H.sub.7 3-CF.sub.3C.sub.6 H.sub.4 74-78tert.-C.sub.4 H.sub.9 i-C.sub.3 H.sub.7 120-122tert.-C.sub.4 H.sub.9 tert-C.sub.4 H.sub.9 129-133tert.-C.sub.4 H.sub.9 C.sub.6 H.sub.5 121-122tert.-C.sub.4 H.sub.9 4-ClC.sub.6 H.sub.4 158-161tert.-C.sub.4 H.sub.9 3-CF.sub.3 C.sub.6 H.sub.4 104-108cyclo-C.sub.6 H.sub.11 i-C.sub.3 H.sub.7 139-140cyclo-C.sub.6 H.sub.11 tert-C.sub.4 H.sub.9 121-122cyclo-C.sub.6 H.sub.11 cyclo-C.sub.3 H.sub.5 144-146cyclo-C.sub.6 H.sub.11 cyclo-C.sub.6 H.sub.11cyclo-C.sub.6 H.sub.11 C.sub.6 H.sub.5 180-181Tetrahydropyran-3-yl i-C.sub.3 H.sub.7 102-104Tetrahydropyran-3-yl tert-C.sub.4 H.sub.9 110-114Tetrahydropyran-3-yl cyclo-C.sub.3 H.sub.5 108-110Tetrahydropyran-3-yl cyclo-C.sub.6 H.sub.11Tetrahydropyran-3-yl C.sub.6 H.sub.5 149-151C.sub.6 H.sub.5 i-C.sub.3 H.sub.7C.sub.6 H.sub.5 tert-C.sub.4 H.sub.9C.sub.6 H.sub.5 cyclo-C.sub.3 H.sub.5C.sub.6 H.sub.5 cyclo-C.sub.6 H.sub.11C.sub.6 H.sub.5 C.sub.6 H.sub.54-ClC.sub.6 H.sub.4 i-C.sub.3 H.sub.7 166-1714-ClC.sub.6 H.sub.4 tert-C.sub.4 H.sub.9 128-1324-ClC.sub.6 H.sub.4 C.sub.6 H.sub.5 229-2324-ClC.sub.6 H.sub.4 4-ClC.sub.6 H.sub.44-ClC.sub.6 H.sub.4 3-CF.sub.3C.sub.6 H.sub.4 163-165cyclo-C.sub.3 H.sub.5 i-C.sub.3 H.sub.7 114-117cyclo-C.sub.3 H.sub.5 tert-C.sub.4 H.sub. 9 106-107cyclo-C.sub.3 H.sub.5 C.sub.6 H.sub.5 180-186______________________________________ mp. [.degree.C.]/ .sup.1 H.NMRR.sup.1 R.sup.4 (CDCl.sub.3) [ppm]______________________________________i-C.sub.3 H.sub.7 cyclo-C.sub.5 H.sub.9 119-121i-C.sub.3 H.sub.7 Tetrahydrofur-3-yl 75-78i-C.sub.3 H.sub.7 Thiazol-2-yl 165-168i-C.sub.3 H.sub.7 5-Methylthiazol2-yl 149-153i-C.sub.3 H.sub.7 5-Ethylthiazol2-yl 157-163i-C.sub.3 H.sub.7 5-n-Propylthiazol-yl 140-145i-C.sub.3 H.sub.7 CH(CH.sub.3)CH.sub.2 CN 88-92i-C.sub.3 H.sub.7 C(CH.sub.3).sub.2CH.sub.2 CN 95-97i-C.sub.3 H.sub.7 OC.sub.2 H.sub.5 33-35i-C.sub.3 H.sub.7 Pyrid-2-yl 104-106i-C.sub.3 H.sub.7 Pyrid-3-yl 150-152i-C.sub.3 H.sub.7 Pyrid-4-yl 185-187i-C.sub.3 H.sub.7 Pyrimid-2-yl 94-99n-C.sub.3 H.sub.7 i-C.sub.3 H.sub.7 108-110n-C.sub.3 H.sub.7 cyclo-C.sub.3 H.sub.5 104-106n-C.sub.3 H.sub.7 tert-C.sub.4 H.sub.9 85-86n-C.sub.3 H.sub.7 C.sub.6 H.sub.5 118-119n-C.sub.3 H.sub.7 cyclo-C.sub.6 H.sub.11 136-137s-C.sub.4 H.sub.9 i-C.sub. 3 H.sub.5 150-152s-C.sub.4 H.sub.9 cyclo-C.sub.3 H.sub.5 107-111s-C.sub.4 H.sub.9 tert-C.sub.4 H.sub.9 138-142s-C.sub.4 H.sub.9 C.sub.6 H.sub.5 99-101i-C.sub.3 H.sub.7 N(CH.sub.3).sub.2 131-133CH.sub.3 N(CH.sub.3).sub.2 111-113CH.sub.3 Morpholino 190-192CH.sub.3 Piperidino 158-161CH.sub.3 CH.sub.3 146-148i-C.sub.3 H.sub.7 Piperidino 133-135i-C.sub.3 H.sub.7 Morpholino 178-179CH.sub.3 C.sub.2 H.sub.5 97-99neo-C.sub.5 H.sub.11 CH.sub.3 128-130neo-C.sub.5 H.sub.11 i-C.sub.3 H.sub.7 85-88neo-C.sub.5 H.sub.11 cyclo-C.sub.3 H.sub.5 109-112neo-C.sub.5 H.sub.11 tert-C.sub.4 H.sub.9 97-99neo-C.sub.5 H.sub.11 C.sub.6 H.sub.5 137-140n-C.sub.4 H.sub.9 CH.sub.3 74-76n-C.sub.4 H.sub.9 i-C.sub.3 H.sub.7 97-100n-C.sub.4 H.sub.9 cyclo-C.sub.3 H.sub.5 82-86n-C.sub.4 H.sub.9 tert-C.sub.4 H.sub.9 60-64n-C.sub.4 H.sub.9 C.sub.6 H.sub.5 118-120cyclo-C.sub.5 H.sub.9 tert-C.sub.4 H.sub.9 114-115cyclo-C.sub. 5 H.sub.9 CH.sub.3 88-89cyclo-C.sub.5 H.sub.9 cyclo-C.sub.3 H.sub.5 108-109cyclo-C.sub.5 H.sub.9 C.sub.6 H.sub.5 146-148n-C.sub.4 H.sub.9 OCH.sub.3 62-66CH.sub.3OCH.sub.2 tert-C.sub.4 H.sub.7 50-55CH.sub.3OCH.sub.2 cyclo-C.sub.3 H.sub.5 55-602-Methoxyphenyl tert-C.sub.4 H.sub.9 119-1202-Methoxyphenyl cyclo-C.sub.3 H.sub.5 160-163i-C.sub.3 H.sub.7 CH.sub.2 -cyclo-C.sub.3 H.sub.5 77-80n-C.sub.4 H.sub.9 CH.sub.2 -cyclo-C.sub.3 H.sub.5 102-105CH.sub.3 OCH(CH.sub.3) tert-C.sub.4 H.sub.9 76-79cyclo-C.sub.3 H.sub.5 cyclo-C.sub.5 H.sub.9 148-1492,6-Difluorophenyl tert-C.sub.4 H.sub.9 118-1222,6-Difluorophenyl cyclo-C.sub.3 H.sub.5 128-132CH.sub.3 cyclo-C.sub.4 H.sub.7 114-115i-C.sub.3 H.sub.7 cyclo-C.sub.4 H.sub.7 84-85CH.sub.3 O tert-C.sub.4 H.sub.9 65-68______________________________________ ##STR20## (VII)R.sup.1 R.sup.3 R.sup.4 pm. [.degree.C.]______________________________________i-C.sub.3 H.sub.7 CH.sub.3 CH.sub.3i-C.sub.3 H.sub.7 C.sub.2 H.sub.5 C.sub.2 H.sub.5 oil______________________________________
EXAMPLE B
65 g of diethyl 3-methylisoxazole-4,5-dicarboxylate, dissolved in 100 ml of ethanol, are added dropwise to 18.9 g of potassium hydroxide in 100 ml of water at room temperature. After 16 hours, the mixture is poured onto 300 ml of water and extracted with ether, and the aqueous phase ia acidified with concentrated hydrochloric acid. Extracting with dichloromethane and evaporating down give 3-methyl-4-ethoxycarbonylisoxazole-5-carboxylic acid as colorless crystals of melting point 54.degree.-58.degree. C.
EXAMPLE C
A solution of 14.9 g of NaOH in 120 ml of water and 150 ml of methanol is added dropwise to 85.5 g of dimethyl 3-ethylisothiazole-4,5-dicarboxylate in 300 ml of methanol, while cooling with ice. After 2 hours, the mixture is evaporated down, 1.5 l of water are added to the residue and the mixture is stirred, and extracted with ether. The aqueous phase is acidified with concentrated hydrochloric acid and extracted by shaking with dichloromethane. The organic phases are evaporated down to give 76.4 g of 3-ethyl-4-methoxycarbonylisothiazole-5-carboxylic acid of melting point 43.degree.-45.degree. C.
For example, the isoxazole(isothiazole)-5-carboxylic acids III can be synthesized similarly to Examples b and c.
______________________________________ ##STR21## (III)R.sup.1 R.sup.5 X mp. [.degree.C.]______________________________________H CH.sub.3 OH C.sub.2 H.sub.5 OH CH.sub.3 SH C.sub.2 H.sub.5 SCH.sub.3 CH.sub.3 OCH.sub.3 CH.sub.3 S 75-81CH.sub.3 C.sub.2 H.sub.5 SC.sub.2 H.sub.5 CH.sub.3 OC.sub.2 H.sub.5 C.sub.2 H.sub.5 OC.sub.2 H.sub.5 C.sub.2 H.sub.5 Sn-C.sub.3 H.sub.7 CH.sub.3 On-C.sub.3 H.sub.7 C.sub.2 H.sub.5 On-C.sub.3 H.sub.7 CH.sub.3 Sn-C.sub.3 H.sub.7 C.sub.2 H.sub.5 Si-C.sub.3 H.sub.7 CH.sub.3 Oi-C.sub.3 H.sub.7 C.sub.2 H.sub.5 Oi-C.sub.3 H.sub.7 CH.sub.3 S oili-C.sub.3 H.sub.7 C.sub.2 H.sub.5 Ss-C.sub.4 H.sub.9 CH.sub.3 Os-C.sub.4 H.sub.9 C.sub.2 H.sub.5 Os-C.sub.4 H.sub.9 CH.sub.3 Ss-C.sub.4 H.sub.9 C.sub.2 H.sub.5 Stert-C.sub.4 H.sub.9 CH.sub.3 Otert-C.sub.4 H.sub.9 C.sub.2 H.sub.5 Otert-C.sub.4 H.sub.9 CH.sub.3 Stert-C.sub.4 H.sub.9 C.sub.2 H.sub.5 Scyclo-C.sub.3 H.sub.5 CH.sub.3 Ocyclo-C.sub.3 H.sub.5 C.sub.2 H.sub.5 Ocyclo-C.sub.3 H.sub.5 CH.sub.3 Scyclo-C.sub.3 H.sub.5 C.sub.2 H.sub.5 Scyclo-C.sub.6 H.sub.11 CH.sub.3 Ocyclo-C.sub.6 H.sub.11 C.sub.2 H.sub.5 Ocyclo-C.sub.6 H.sub.11 CH.sub.3 Scyclo-C.sub.6 H.sub.11 C.sub.2 H.sub.5 STetrahydropyran- CH.sub.3 O3-ylTetrahydropyran- C.sub.2 H.sub.5 O3-ylTetrahydropyran- CH.sub.3 S3-ylTetrahydropyran- C.sub.2 H.sub.5 S3-ylC.sub.6 H.sub.5 CH.sub.3 OC.sub.6 H.sub.5 C.sub.2 H.sub.5 OC.sub.6 H.sub.5 CH.sub.3 S 139-141C.sub.6 H.sub.5 C.sub.2 H.sub.5 S______________________________________
Preparation Examples for compounds I and Ia
EXAMPLE 1
2.9 g of isopropylamine are added dropwise to 10 g of diethyl 3-methylisoxazole-4,5-dicarboxylate, dissolved in 100 ml of methanol, and the mixture is then refluxed. After 7 hours the mixture is evaporated down and the remaining oil is chromatographed over silica gel (using 9:1 toluene/acetone). Methyl 5-isopropylaminocarbonyl-3-methylisoxazole-4-carboxylate is obtained as colorless crystals of melting point 64.degree.-66.degree. C. (compound No. 1005).
EXAMPLE 2
2.6 g of the ester from Example 1 and 0.8 g of potassium hydroxide in 20 ml of water and 20 ml of ethanol are stirred for 16 hours at room temperature. Thereafter, the mixture is diluted with water, acidified with concentrated hydrochloric acid and extracted by shaking with dichloroaminocarbonyl-3-methylisoxazole-4-carboxylic acid as colorless crystals of melting point 86.degree.-92.degree. C. (compound No. 1004).
EXAMPLE 3
70 ml of n-butyllithium (1.6 molar solution in n-hexane) are added dropwise, at -70.degree. C. to 9.0 g of the anilide from Example a, dissolved in 200 ml of absolute tetrahydrofuran. Stirring is carried out for half an hour and the reaction mixture is poured onto 500 g of solid carbon dioxide. After standing overnight, the mixture is evaporated down and the residue is partitioned between H.sub.2 O, sodium hydroxide solution and ethyl acetate. By evaporating down the ethyl acetate phase, 2.0 g of starting material can be recovered. Acidification of the aqueous phase with concentrated hydrochloric acid and filtration under suction give 8.30 g of 5-anilinocarbonyl-3-ethylisoxazole-4-carboxylic acid as colorless crystals of melting point 150.degree.-152.degree. C. (compound No. 1015).
EXAMPLE 4
5.0 g of 5-tert-butylaminocarbonyl-3-methylisoxazole-4-carboxylic acid are dissolved in 200 ml of methanol, and 5 ml of concentrated H.sub.2 SO.sub.4 are added. After 2 days, the mixture is evaporated down, the residue is partitioned between ethyl acetate and water and the organic phase is evaporated down. 4.0 g of methyl 5-tert-butylaminocarbonyl-3-methylisoxazole-4-carboxylate are obtained as a colorless oil (compound No. 1007). H-NMR (CDCl.sub.3): d=1.48 (s; 9H), 2.50 (s; 3H), 3.99 (s; 1H), 9.42 (bs; 1H, NH).
EXAMPLE 5
a) 3-Ethyl-4-methoxycarbonylisothiazole-5-carbonyl chloride
73 g of the carboxylic acid from Example c and 80 g of thionyl chloride in 200 ml of toluene are refluxed in the presence of a little dimethylformamide until the evolution of gas is complete. The crude carbonyl chloride which remains in quantitative yield after evaporation is directly reacted further.
b) Methyl 5-isopropylaminocarbonyl-3-ethylisothiazole-4-carboxylate
8.4 g of isopropylamine are slowly added dropwise to 16.5 g of the crude acyl chloride from a) in 200 ml of dichloromethane, while cooling with ice. Stirring is carried out overnight, hydrolysis is effected with 150 ml of water and the organic phase is separated off, washed with bicarbonate solution, dilute hydrochloric acid and water and then evaporated down. 16.2 g of methyl 5-isopropylaminocarbonyl-3-ethylthiazole-4-carboxylate of melting point 55.degree.-56.degree. C. (compound No. 3007) are obtained.
EXAMPLE 6
2.8 g of KOH in 30 ml of water are added to 11 g of the ester from Example 5 in 50 ml of ethanol, and the mixture is stirred overnight at room temperature. It is diluted with 150 ml of water and extracted with ether, and the aqueous phase is acidified with concentrated hydrochloric acid. Extraction by shaking with dichloromethane and evaporation give 10 g of 5-isopropylaminocarbonyl-3-ethylisothiazole-4-carboxylic acid of melting point 138.degree.-140.degree. C. (compound No. 3006).
EXAMPLE 7
4.0 g of methyl 5-tert-butyaminocarbonyl-3-methylisoxazole-4-carboxylate and 50 ml of concentrated ammonia are refluxed for 3 hours. After cooling, the mixture is diluted with water and extracted with dichlormethane and the organic phase is evaporated down. 5-tert-butylaminocarbonyl-3-methylisoxazole-4-carboxamide is obtained as colorless crystals of melting point 155.degree.-158.degree. C. (compound No. 1).
EXAMPLE 8
56 ml of butyllithium (1.6 molar solution in n-hexane) are added dropwise, at -78.degree. C., to 8 g of the tertbutylamide of 3-methylisoxazole-5-carboxylic acid in 150 ml of tetrahydrofuran. The mixture is stirred for 1 hour, after which 22 ml of dimethylformamide are slowly added dropwise. The mixture is allowed to reach room temperature overnight and is hydrolyzed with water, neutralized with concentrated hydrochloric acid and extracted with ether. The oil which remains after evaporation is chromatographed over silica gel sing cyclohexane/ethyl acetate. The tert-butylamide of 4-formyl-3-methylisoxazole-5-carboxylic acid is obtained as the first fraction, in the form of pale yellow crystals of melting point 36.degree.-38.degree. C. (compound No. 2).
EXAMPLE 9
a) 3-Methyl-4-ethoxycarbonylixoxazole-5-carbonyl chloride
13.3 g of carboxylic acid from Example b and 20 ml of thionyl chloride are refluxed in the presence of a little dimethylformamide until the evolution of gas is complete. The crude carbonyl chloride which remains in quantitative yield after evaporation is directly reacted further.
b) 3.4 g of diethylamine are slowly added dropwise to 5 g of the crude acyl chloride from a) in 100 g of dichloromethane, while cooling with ice. Stirring is carried out overnight, hydrolysis is effected with water and the organic phase is separated off, washed with bicarbonate and then evaporated down. 5.0 g of ethyl 5-diethylaminocarbonyl-3-methylisoxazole-4-carboxylate are obtained as a brown oil (compound No. 3).
H-NMR (CDCl.sub.3): .delta.=1.15 (t; 3H), 1.27 and 1.31 (2t; 6H), 2.50 (s; 3H), 3.17 (q; 2H), 3.58 (q; 2H), 4.28 (q; 2H).
EXAMPLE 10
5.0 g of the ester from Example 9 and 1.4 g of potassium hydroxide in 10 ml of water and 20 ml of ethanol are stirred at room temperature. When the reaction is complete, the mixture is diluted with water and extracted with dichloromethane. Thereafter, the aqueous phase is acidified with hydrochloric acid and extracted with dichlormethane, and the organic phase is evaporated down. 3.0 g of 5-diethylaminocarbonyl-3-methylisoxazole-4-carboxylic acid are obtained as a pale oil (compound No. 4).
H-NMR (CDCl.sub.3 : .delta.=1.28 and 1.32 (2t; 6H), 2.60 (s; 3H), 3.59 and 3.62 (2q; 4H), 10.50 (bs; 1H, COOH).
EXAMPLE 11
A mixture of 1.2 g of 2-methylpropane-2-thiol, 3.0 g of 5-tert-butylaminocarbonyl-3-methylisoxazole-4-carboxylic acid and 5.9 g of tri-n-butylamine in 20 ml of dichloromethane is added dropwise to a stirred suspension of 4.1 g of 1-methyl-2-chloropyridinium iodide in 40 ml of dichloromethane at room temperature. The mixture is refluxed for 3 hours, the solvent is stripped off under reduced pressure and the crude product is purified by column chromatography over silica gel. 2.1 g of the tert-butyl thioester of 5-tert-butylaminocarbonyl-3-methylisoxazole-4-carboxylic acid are obtained as a yellow oil (compound No. 2003).
For example, the compounds mentioned in Tables 1 to 3 below can be prepared similarly to Examples 1 to 10.
TABLE 1__________________________________________________________________________ ##STR22## mp [.degree.C.]/.sup.1 H-NMRNo. R.sup.1 R.sup.5 R.sup.4 (CDCl.sub.3)__________________________________________________________________________ [ppm]1001 H H i-C.sub.3 H.sub.71002 H H tert.-C.sub.4 H.sub.9 oil 1.55(s; 9H), 7.50(bs; 1H, NH), 8.78(s; 1H)1003 CH.sub.3 H H 266-2681004 CH.sub.3 H i-C.sub.3 H.sub.7 86-921005 CH.sub.3 CH.sub.3 i-C.sub.3 H.sub.7 64-661006 CH.sub.3 H tert.-C.sub.4 H.sub.9 92-941007 CH.sub.3 CH.sub.3 tert.-C.sub.4 H.sub.91008 CH.sub.3 H 1-ethylcyclohexyl 119-1211009 CH.sub.3 H 4-methyltetrahydro- 80-87 pyran-4-yl1010 CH.sub.3 H C.sub.6 H.sub.5 204-2101011 CH.sub.3 H 4-ClC.sub.6 H.sub.4 233-2371012 CH.sub.3 H 3-CF.sub.3C.sub.6 H.sub.4 188-1911013 C.sub.2 H.sub.5 H i-C.sub.3 H.sub.7 63-661014 C.sub.2 H.sub.5 H tert.-C.sub.4 H.sub.9 53-581015 C.sub.2 H.sub.5 H C.sub.6 H.sub.5 150-1521016 C.sub.2 H.sub.5 H 4-ClC.sub.6 H.sub.4 193-1961017 C.sub.2 H.sub.5 h 3-CF.sub.3C.sub.6 H.sub.4 160-1621018 i-C.sub.3 H.sub.7 H H1019 i-C.sub.3 H.sub.7 H CH.sub.3 147-1481020 i-C.sub.3 H.sub.7 H C.sub.2 H.sub.5 100-1011021 i-C.sub.3 H.sub.7 H n-C.sub.3 H.sub.7 85-861022 i-C.sub.3 H.sub.7 H i-C.sub.3 H.sub.7 98-991023 i-C.sub.3 H.sub.7 H n-C.sub.4 H.sub.9 96-971024 i-C.sub.3 H.sub.7 H i-C.sub.4 H.sub.9 112-1141025 i-C.sub.3 H.sub.7 H sec-C.sub.4 H.sub.9 oil 1.00(t; 3H), 1.32(d; 3H), 1.37(d; 6H), 1.64(quint; 2H), 3.78(sept; 1H), 4.15(m; 1H), 7.00(bs; 1H, NH)1026 i-C.sub.3 H.sub.7 H tert.-C.sub.4 H.sub.9 94-981027 i-C.sub.3 H.sub.7 H C(CH.sub.3).sub.2 C.sub.2 H.sub.5 44-461028 i-C.sub.3 H.sub.7 H C(CH.sub.3).sub.2 C.sub.3 H.sub.7 52-531029 i-C.sub.3 H.sub.7 H C(CH.sub.3).sub.2 CH.sub.2 C(CH.sub.3).sub. 3 89-911030 i-C.sub.3 H.sub.7 H C(CH.sub.3).sub.2 CH.sub.2 SCH.sub.3 oil 1.35(d; 3H), 1.56(s; 6H), 2.18(s; 3H), 2.99(s; 2H), 3.77(sept; 1H), 7.30(bs; 1H, NH)1031 i-C.sub.3 H.sub.7 H CH.sub.2 CH.sub.2 SCH.sub.31032 i-C.sub.3 H.sub.7 H CH.sub.2 CH.sub.2 CH.sub.2 SCH.sub.3 116-1181033 i-C.sub.3 H.sub.7 H CH.sub.2 CH.sub.2 OCH.sub.3 69-711034 i-C.sub.3 H.sub.7 H CH.sub.2 CH.sub.2 N(CH.sub.3).sub.21035 i-C.sub.3 H.sub.7 H cyclo-C.sub.3 H.sub.5 74-761036 i-C.sub.3 H.sub.7 H cyclo-C.sub.6 H.sub.11 112-1141037 i-C.sub.3 H.sub.7 H 1-ethylcyclohexyl 89-901038 i-C.sub.3 H.sub.7 H 4-methyltetrahydro- 129-130 pyran-4-yl1039 i-C.sub.3 H.sub.7 H 1-C(CH.sub.3).sub.2 -cycloC.sub.6 H.sub.11 144-1461040 i-C.sub.3 H.sub.7 H CH.sub.2 CHCH.sub.2 92-941041 i-C.sub.3 H.sub.7 H C(CH.sub.3).sub.2 CHCH.sub.2 oil; 1.35(d; 6H), 1.62(s; 6H), 3.78(sept; 1H), 5.20(d; 1H), 5.25(d; 1H), 6.10(dd; 1H), 7.10(bs; 1H, NH)1042 i-C.sub.3 H.sub.7 H CH.sub.2 C.sub.6 H.sub.5 oil 1.30(d; 6H), 3.74(sept; 1H), 4.70(d; 2H), 7.35(bs; 5H), 7.85(bt; 1H, NH)1043 i-C.sub.3 H.sub.7 H C(CH.sub.3).sub.2 C.sub.6 H.sub.51044 i-C.sub.3 H.sub.7 H CH.sub.2 C(CH.sub.3).sub.3 761045 i-C.sub.3 H.sub.7 H C.sub.6 H.sub.5 138-1401046 i-C.sub.3 H.sub.7 H 4-ClC.sub.6 H.sub.4 170-1731047 i-C.sub.3 H.sub.7 H 3-CF.sub.3C.sub.6 H.sub.4 1271048 tert.-C.sub.4 H.sub.9 H i-C.sub.3 H.sub.7 84-851049 tert.-C.sub.4 H.sub.9 H tert.-C.sub.4 H.sub.9 129-1331050 tert.-C.sub. 4 H.sub.9 H C.sub.6 H.sub.5 132-1371051 tert.-C.sub.4 H.sub.9 H 4-ClC.sub.6 H.sub.4 188-1911052 tert.-C.sub.4 H.sub.9 H 3-CF.sub.3C.sub.6 H.sub.4 160-1621053 cyclo-C.sub.6 H.sub.11 H i-C.sub.3 H.sub.7 116-1181054 cyclo-C.sub.6 H.sub.11 H tert.-C.sub.4 H.sub.9 158-1591055 cyclo-C.sub.6 H.sub.11 H cyclo-C.sub.3 H.sub.5 142-1431056 cyclo-C.sub.6 H.sub.11 H cyclo-C.sub.6 H.sub.111057 cyclo-C.sub.6 H.sub.11 H C.sub.6 H.sub.5 198-1991058 4-ClC.sub.6 H.sub.4 H i-C.sub.3 H.sub.7 165-1681059 4-ClC.sub.6 H.sub.4 H tert.-C.sub.4 H.sub.9 165-1681060 4-ClC.sub.6 H.sub.4 H C.sub.6 H.sub.5 2201061 4-ClC.sub.6 H.sub.4 H 4-ClC.sub.6 H.sub.41062 4-ClC.sub.6 H.sub.4 H 3-CF.sub.3C.sub.6 H.sub.4 209-2111063 i-C.sub.3 H.sub.7 succinimido cyclo-C.sub.3 H.sub.5 108-1091064 CH.sub.3 H C(CH.sub.3).sub.2 CCH 80-871065 CH.sub.3 C.sub.2 H.sub.5 C(CH.sub.3).sub.2 CCH 82-861066 CH.sub.3 Na.sup..sym. tert.-C.sub.4 H.sub.9 2201067 CH.sub.3 K.sup..sym. tert.-C.sub.4 H.sub.9 2881068 CH.sub.3 H.sub.3 N.sup..sym. CH(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.9 184-1871069 CH.sub.3 H.sub.3 N.sup..sym.CH.sub.2 CH.sub.2 OH tert.-C.sub.4 H.sub.9 124-1261070 C.sub.2 H.sub.5 Na.sup..sym. tert.-C.sub.4 H.sub.9 1501071 C.sub.2 H.sub.5 K.sup..sym. tert.-C.sub.4 H.sub.9 2201072 C.sub.2 H.sub.5 H.sub.3 N.sup..sym.CH(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.9 170-1721073 C.sub.2 H.sub.5 H.sub.3 N.sup..sym.CH.sub.2 CH.sub.2 OH tert.-C.sub.4 H.sub.9 105-1081074 C.sub.2 H.sub.5 succinimido tert.-C.sub.4 H.sub.9 163-1651075 C.sub.2 H.sub.5 NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.9 68-701076 C.sub.2 H.sub.5 CH.sub.2 CCH tert.-C.sub.4 H.sub.9 oil 135(t; 3H), 1.48(s; 9H), 2.63(t; 1H), 2.96; 4.98(d; 2H), 8.95(bs; 1H, NH)1077 C.sub.2 H.sub.5 CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5 tert.-C.sub.4 H.sub.9 74-761078 cyclo-C.sub.3 H.sub.5 H i-C.sub.3 H.sub.7 78-801079 cyclo-C.sub.3 H.sub.5 H tert.-C.sub.4 H.sub.9 87-881080 cyclo-C.sub.3 H.sub.5 H C.sub.6 H.sub.5 162-1631081 cyclo-C.sub.6 H.sub.11 succinimido i-C.sub.3 H.sub.7 126-1271082 cyclo-C.sub.6 H.sub.11 succinimido tert.-C.sub.4 H.sub.9 172-1741083 cyclo-C.sub.6 H.sub.11 succinimido C.sub.6 H.sub.5 176-1771084 tetrahydro- H i-C.sub.3 H.sub.7 157-160 pyran-3-yl1085 tetrahydro- H tert.-C.sub.4 H.sub.9 91-95 pyran-3-yl1086 tetrahydro- H cyclo-C.sub.3 H.sub.5 158-160 pyran-3-yl1087 tetrahydro- H C.sub.6 H.sub.5 152-157 pyran-3-yl1088 CH.sub.3 pyrid-3-yl tert.-C.sub.4 H.sub.9 methyl1089 CH.sub.3 thien-2-yl- tert.-C.sub.4 H.sub.9 methyl1090 CH.sub.3 CH.sub.2CH.sub.2N(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.91091 CH.sub.3 ##STR23## tert.-C.sub.4 H.sub.91092 CH.sub.3 CH.sub.2CF.sub.3 tert.-C.sub.4 H.sub.91093 CH.sub.3 CH.sub.2C(CH.sub.3)CH.sub.2 tert.-C.sub.4 H.sub.91094 CH.sub.3 CH.sub.2 C(Cl)CH.sub.2 tert.-C.sub.4 H.sub.91095 CH.sub.3 CH.sub.2CCCH.sub.2 OH tert.-C.sub.4 H.sub.91096 CH.sub.3 ##STR24## tert.-C.sub.4 H.sub.91097 CH.sub.3 ##STR25## tert.-C.sub.4 H.sub.91098 CH.sub.3 ##STR26## tert.-C.sub.4 H.sub.91099 CH.sub.3 phenethyl tert.-C.sub.4 H.sub.91100 CH.sub.3 CH(C.sub.6 H.sub.5)COOCH.sub.3 tert.-C.sub.4 H.sub.91101 CH.sub.3 cyclo-C.sub.6 H.sub.11 tert.-C.sub.4 H.sub.91102 CH.sub.3 CH.sub. 2OCH.sub.2C.sub.6 H.sub.5 tert.-C.sub.4 H.sub.91103 CH.sub.3 tetrahydro- tert.-C.sub.4 H.sub.9 pyran-2-yl1104 CH.sub.3 tetrahydro- tert.-C.sub.4 H.sub.9 fur-2-yl1105 CH.sub.3 (4-bromobenzoyl)- tert.-C.sub.4 H.sub.9 methyl1106 CH.sub.3 (4-methoxybenzoyl)- tert.-C.sub.4 H.sub.9 methyl1107 CH.sub.3 CH(COOCH.sub.3).sub.2 tert.-C.sub.4 H.sub.91108 CH.sub.3 phthalimidomethyl tert.-C.sub.4 H.sub.91109 CH.sub.3 CH.sub.2CH.sub.2Si(CH.sub.3).sub.3 tert.-C.sub.4 H.sub.91110 CH.sub.3 CH.sub.2CH.sub.2ONC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.91111 CH.sub.3 CH.sub.2PO(OC.sub.2 H.sub.5).sub.2 tert.-C.sub.4 H.sub.91112 CH.sub.3 fur-2-yl-methyl tert.-C.sub.4 H.sub.91113 CH.sub.3 tetrahydrofur-2- tert.-C.sub.4 H.sub.9 yl-methyl1114 CH.sub.3 pyrid-2-ylmethyl tert.-C.sub.4 H.sub.91115 CH.sub.3 pyrid-4-ylmethyl tert.-C.sub.4 H.sub.91116 CH.sub.3 piperidino tert.-C.sub.4 H.sub.91117 CH.sub.3 phthalimido tert.-C.sub.4 H.sub.91118 CH.sub.3 ##STR27## tert.-C.sub.4 H.sub.91119 CH.sub.3 NCHC.sub.6 H.sub.5 tert.-C.sub.4 H.sub.91120 CH.sub.3 ##STR28## tert.-C.sub.4 H.sub.91121 CH.sub.3 CH(CH.sub.3)CH(OCH.sub.3).sub.2 tert.-C.sub.4 H.sub.91122 CH.sub.3 CH.sub.2CON(C.sub.2 H.sub.5).sub.2 tert.-C.sub.4 H.sub.91123 CH.sub.3 N(C.sub.2 H.sub.5).sub.2 tert.-C.sub.4 H.sub.91124 C.sub.2 H.sub.5 cyclo-C.sub.6 H.sub.11 tert.-C.sub.4 H.sub.91125 C.sub.2 H.sub.5 CH.sub.2OCH.sub.2C.sub.6 H.sub.5 tert.-C.sub.4 H.sub.91126 C.sub.2 H.sub.5 tetrahydro- tert.-C.sub.4 H.sub.9 pyran-2-yl1127 C.sub.2 H.sub.5 tetrahydro- tert.-C.sub.4 H.sub.9 fur-2-yl1128 C.sub.2 H.sub.5 (4-bromobenzoyl)- tert.-C.sub.4 H.sub.9 methyl1129 C.sub.2 H.sub.5 (4-methoxybenzoyl) tert.-C.sub.4 H.sub.9 methyl1130 C.sub.2 H.sub.5 CH(COOCH.sub.3).sub.2 tert.-C.sub.4 H.sub.91131 C.sub.2 H.sub.5 phthalimidomethyl tert.-C.sub.4 H.sub.91132 C.sub.2 H.sub.5 CH.sub.2CH.sub.2Si(CH.sub.3).sub.3 tert.-C.sub.4 H.sub.91133 C.sub.2 H.sub.5 CH.sub.2CH.sub.2ONC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.91134 C.sub.2 H.sub.5 CH.sub.2PO(OC.sub.2 H.sub.5).sub.2 tert.-C.sub.4 H.sub.91135 C.sub.2 H.sub.5 fur-2-ylmethyl tert.-C.sub.4 H.sub.91136 C.sub.2 H.sub.5 tetrahydrofur-2- tert.-C.sub.4 H.sub.9 yl-methyl1137 C.sub.2 H.sub.5 pyrid-2-yl-methyl tert.-C.sub.4 H.sub.91138 C.sub.2 H.sub.5 pyrid-4-yl-methyl tert.-C.sub.4 H.sub.91139 C.sub.2 H.sub.5 pyrid-3-yl-methyl tert.-C.sub.4 H.sub.91140 C.sub.2 H.sub.5 thien-2-yl-methyl tert.-C.sub.4 H.sub.91141 C.sub.2 H.sub.5 CH.sub.2CH.sub.2N(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.91142 C.sub.2 H.sub.5 ##STR29## tert.-C.sub.4 H.sub.91143 C.sub.2 H.sub.5 CH.sub.2CF.sub.3 tert.-C.sub.4 H.sub.91144 C.sub.2 H.sub.5 CH.sub.2C(CH.sub.3)CH.sub.2 tert.-C.sub.4 H.sub.91145 C.sub.2 H.sub.5 CH.sub.2 C(Cl)CH.sub.2 tert.-C.sub.4 H.sub.91146 C.sub.2 H.sub.5 CH.sub.2 C CH.sub.2 OH tert.-C.sub.4 H.sub.91147 C.sub.2 H.sub.5 ##STR30## tert.-C.sub.4 H.sub.91148 C.sub.2 H.sub.5 ##STR31## tert.-C.sub.4 H.sub.91149 C.sub.2 H.sub.5 ##STR32## tert.-C.sub.4 H.sub.91150 C.sub.2 H.sub.5 phenethyl tert.-C.sub.4 H.sub.91151 C.sub.2 H.sub.5 CH(C.sub.6 H.sub.5)COOCH.sub.3 tert.-C.sub.4 H.sub.91152 C.sub.2 H.sub.5 piperidino tert.-C.sub.4 H.sub.91153 C.sub.2 H.sub.5 phthalimido tert.-C.sub.4 H.sub.91054 C.sub.2 H.sub.5 ##STR33## tert.-C.sub.4 H.sub.91055 C.sub.2 H.sub.5 NCHC.sub. 6 H.sub.5 tert.-C.sub.4 H.sub.91156 C.sub.2 H.sub.5 ##STR34## tert.-C.sub.4 H.sub.91157 C.sub.2 H.sub.5 CH(CH.sub.3)CH(OCH.sub.3).sub.2 tert.-C.sub.4 H.sub.91158 C.sub.2 H.sub.5 CH.sub.2CON(C.sub.2 H.sub.5).sub.2 tert.-C.sub.4 H.sub.91159 C.sub.2 H.sub.5 N(C.sub.2 H.sub.5).sub.2 tert.-C.sub.4 H.sub.91160 i-C.sub.3 H.sub.7 cyclo-C.sub.6 H.sub.11 tert.-C.sub.4 H.sub.91161 i-C.sub.3 H.sub.7 CH.sub.2OCH.sub.2C.sub.6 H.sub.5 tert.-C.sub.4 H.sub.91162 i-C.sub.3 H.sub.7 tetrahydro- tert.-C.sub.4 H.sub.9 pyran-2-yl1163 i-C.sub.3 H.sub.7 tetrahydro- tert.-C.sub.4 H.sub.9 fur-2-yl1164 i-C.sub.3 H.sub.7 (4-bromo-benzoyl)- tert.-C.sub.4 H.sub.9 methyl1165 i-C.sub.3 H.sub.7 (4-methoxybenzoyl) tert.-C.sub.4 H.sub.9 methyl1166 i-C.sub.3 H.sub.7 CH(COOCH.sub.3).sub.2 tert.-C.sub.4 H.sub.91167 i-C.sub.3 H.sub.7 phthalimidomethyl tert.-C.sub.4 H.sub.91168 i-C.sub.3 H.sub.7 CH.sub.2CH.sub.2Si(CH.sub.3).sub.3 tert.-C.sub.4 H.sub.9 64-691169 i-C.sub.3 H.sub.7 CH.sub.2CH.sub.2ONC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.91170 i-C.sub.3 H.sub.7 CH.sub.2PO(OC.sub.2 H.sub.5).sub.2 tert.-C.sub.4 H.sub.91171 i-C.sub.3 H.sub.7 fur-2-ylmethyl tert.-C.sub.4 H.sub.91172 i-C.sub.3 H.sub.7 tetrahydrofur-2- tert.-C.sub.4 H.sub.9 yl-methyl1173 i-C.sub.3 H.sub.7 pyrid-2-yl-methyl tert.-C.sub.4 H.sub.9 oil; 1.30(s; 6H) 1.44(s; 9H), 3.40(sept; 1H) 5.52(s; 2H) 7.20-8.64(m; 4H), 8.60(bs; 1H, NH)1174 i-C.sub.3 H.sub.7 pyrid-4-yl-methyl tert.-C.sub.4 H.sub.91175 i-C.sub.3 H.sub.7 pyrid-3-yl-methyl tert.-C.sub.4 H.sub.91176 i-C.sub.3 H.sub.7 thien-2-yl-methyl tert.-C.sub.4 H.sub.91177 i-C.sub.3 H.sub.7 CH.sub.2CH.sub.2N(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.91178 i-C.sub.3 H.sub.7 ##STR35## tert.-C.sub.4 H.sub.91179 i-C.sub.3 H.sub.7 CH.sub.2CF.sub.3 tert.-C.sub.4 H.sub.91352 i-C.sub.3 H.sub.7 CH.sub.2C(CH.sub.3)CH.sub.2 tert.-C.sub.4 H.sub.91153 i-C.sub.3 H.sub.7 CH.sub.2 C(Cl)CH.sub.2 tert.-C.sub.4 H.sub.91154 i-C.sub.3 H.sub.7 CH.sub.2CCCH.sub.2 OH tert.-C.sub.4 H.sub.91155 i-C.sub.3 H.sub.7 ##STR36## tert.-C.sub.4 H.sub.91156 i-C.sub.3 H.sub.7 ##STR37## tert.-C.sub.4 H.sub.91157 i-C.sub.3 H.sub.7 ##STR38## tert.-C.sub.4 H.sub.91180 i-C.sub.3 H.sub.7 phenethyl tert.-C.sub.4 H.sub.91181 i-C.sub.3 H.sub.7 CH(C.sub.6 H.sub.5)COOCH.sub.3 tert.-C.sub.4 H.sub.91182 i-C.sub.3 H.sub.7 piperidino tert.-C.sub.4 H.sub.91183 i-C.sub.3 H.sub.7 phthalimido tert.-C.sub.4 H.sub.91184 i-C.sub.3 H.sub.7 ##STR39## tert.-C.sub.4 H.sub.91185 i-C.sub.3 H.sub.7 NCHC.sub.6 H.sub.5 tert.-C.sub.4 H.sub.91186 i-C.sub.3 H.sub.7 ##STR40## tert.-C.sub.4 H.sub.91187 i-C.sub.3 H.sub.7 CH(CH.sub.3 CH)(OCH.sub.3).sub.2 tert.-C.sub.4 H.sub.91188 i-C.sub.3 H.sub.7 CH.sub.2CON(C.sub.2 H.sub.5).sub.2 tert.-C.sub.4 H.sub.9 91-931189 i-C.sub.3 H.sub.7 N(C.sub.2 H.sub.5).sub.2 tert.-C.sub.4 H.sub.91190 CH.sub.3 NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.9 108-1091191 CH.sub.3 cyclohexanimino tert.-C.sub.4 H.sub.9 91-921192 CH.sub.3 NC(cyclo-C.sub.3 H.sub.5).sub.2 tert.-C.sub.4 H.sub.9 50-521193 CH.sub.3 H N(CH.sub.3).sub.2 225-2271194 CH.sub.3 H piperidino 162-1641195 CH.sub.3 CH.sub.2CCH tert.-C.sub.4 H.sub.9 90-951197 CH.sub.3 2-NO.sub.2 -4-FC.sub.6 H.sub.3 tert.-C.sub.4 H.sub.9 oil; 1.44(s; 9H), 2.59(s; 3H), 7.24 and 8.30(m; 3H), 8.16(bs; 1H, NH)1198 CH.sub.3 3,5-(CF.sub.3).sub.2C.sub.6 H.sub.3 tert.-C.sub.4 H.sub.9 156-1591199 CH.sub.3 H CH.sub.3 192-1971200 CH.sub.3 H OC.sub.2 H.sub.5 145-1481201 CH.sub.3 H cyclo-C.sub.4 H.sub.7 141-1421202 CH.sub.3 H cyclo-C.sub.3 H.sub.5 135-1371203 CH.sub.3 NC(CH.sub.3).sub.2 cyclo-C.sub.3 H.sub.5 91-931204 CH.sub.3 H C.sub.2 H.sub.5 151-1541205 CH.sub.3 NC(CH.sub.3).sub.2 cyclo-C.sub.4 H.sub.7 77-791207 CH.sub.3 CH.sub.2 CO.sub.2 CH.sub.3 tert.-C.sub.4 H.sub.9 88-891208 C.sub.2 H.sub.5 succinimido i-C.sub.3 H.sub.7 132-1361209 n-C.sub.3 H.sub.7 H cyclo-C.sub.6 H.sub.11 132-1341210 n-C.sub.3 H.sub.7 H tert.-C.sub.4 H.sub.9 82-831211 n-C.sub.3 H.sub.7 NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.9 66-681212 n-C.sub.3 H.sub.7 succinimido tert.-C.sub.4 H.sub.9 126-1291213 n-C.sub.3 H.sub.7 succinimido cyclo-C.sub.3 H.sub.5 104-1061214 n-C.sub. 3 H.sub.7 NC(CH.sub.3).sub.2 cyclo-C.sub.3 H.sub.5 oil 0.70(m; 2H), 0.90(m; 2H), 1.00(t; 3H), 1.78(m; 2H), 2.16 and 2.19(2s; 6H), 2.92(t; 2H), 3.00(m; 1H), 9.24(bs; 1H, NH)1215 n-C.sub.3 H.sub.7 H cyclo-C.sub.3 H.sub.5 104-1061216 n-C.sub.3 H.sub.7 H i-C.sub.3 H.sub.7 70-711217 n-C.sub.3 H.sub.7 NC(CH.sub.3).sub.2 i-C.sub.3 H.sub.7 72-731218 n-C.sub.3 H.sub.7 NC(CH.sub.3).sub.2 cyclo-C.sub.6 H.sub.11 110-1111219 n-C.sub.3 H.sub.7 H C.sub.6 H.sub.5 165-1661220 i-C.sub.3 H.sub.7 NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.9 112-1131221 i-C.sub.3 H.sub.7 ##STR41## tert.-C.sub.4 H.sub.9 83-861222 i-C.sub.3 H.sub.7 cyclohexanimino tert.-C.sub.4 H.sub.9 91-941223 i-C.sub.3 H.sub.7 NC(cyclo-C.sub.3 H.sub.5).sub.2 tert.-C.sub.4 H.sub.9 70-751224 i-C.sub.3 H.sub.7 NC(CH.sub.3).sub.2 tetrahydrofur-3-yl 104-1061225 i-C.sub.3 H.sub.7 succinimido tetrahydrofur-3-yl 160-1621226 i-C.sub.3 H.sub.7 H tetrahydrofur-3-yl oil 1.33(d; 6H), 2.40(m; 2H), 3.75(sept; 1H), 4.00(m; 4H), 4.75(m; 1H), 8.25(d; 1H, NH)1227 i-C.sub.3 H.sub.7 H OC.sub.2 H.sub.5 134-1351228 i-C.sub.3 H.sub.7 succinimido OC.sub.2 H.sub.5 146-1481229 i-C.sub.3 H.sub.7 H thiazol-2-yl 1951230 i-C.sub.3 H.sub.7 H 5-methyl-thiazol- 248 2-yl1231 i-C.sub.3 H.sub.7 H 5-ethyl-thiazol- 228-230 2-yl1232 i-C.sub.3 H.sub.7 H 5-n-propyl-thiazol- 160-163 2-yl1233 i-C.sub.3 H.sub.7 succinimido tert.-C.sub.4 H.sub.9 141-1441234 i-C.sub.3 H.sub.7 H cyclo-C.sub.4 H.sub.7 95-961235 i-C.sub.3 H.sub.7 NC(CH.sub.3).sub.2 cyclo-C.sub.4 H.sub.7 100-1011236 i-C.sub.3 H.sub.7 NC(CH.sub.3).sub.2 N(CH.sub.3).sub.2 129-1311237 i-C.sub.3 H.sub.7 H N(CH.sub.3).sub.2 163-1651238 i-C.sub.3 H.sub.7 H piperidino 167-1681239 i-C.sub.3 H.sub.7 H morpholino 177-1791240 i-C.sub.3 H.sub.7 H cyclo-C.sub.5 H.sub.9 62-651241 i-C.sub.3 H.sub.7 H cyclopropylmethyl 88-901242 i-C.sub.3 H.sub.7 H s-C.sub.4 H.sub.9 oil; 1.00(t; 3H), 1.34(d; 3H), 1.37(d; 6H), 1.66(quint; 2H), 3.78(sept; 1H), 4.17(m; 1H), 7.04(d, 1H, NH)1243 i-C.sub.3 H.sub.7 NC(CH.sub.3).sub.2 s-C.sub.4 H.sub.9 oil; 0.98(t; 3H), 1.26(d, 3H), 1,39(d, 6H) 1.64(quint; 2H), 2.16 and 2.18(2s; 6H) 3.44(sept; 1H), 4.10(m, 1H), 8.54(d, 1H, NH)1244 i-C.sub.3 H.sub.7 H mixture of 197 4-methyl-5-carboxy- thiazol-2-yl and 4-methyl-thiazol-2-yl1245 i-C.sub.3 H.sub.7 CH.sub.2CHCHC.sub.6 H.sub.5 tert.-C.sub.4 H.sub.9 59-631246 i-C.sub.3 H.sub.7 4-CO.sub.2 CH.sub.3 C.sub.6 H.sub.4 tert.-C.sub.4 H.sub.9 143-1451247 i-C.sub.3 H.sub.7 CH.sub.2CH.sub.2CN tert.-C.sub.4 H.sub.9 67-711248 i-C.sub.3 H.sub.7 CH.sub.2CCl.sub.3 tert.-C.sub.4 H.sub.9 72-751249 i-C.sub.3 H.sub.7 4-NHCOCH.sub.3C.sub.6 H.sub.4 tert.-C.sub.4 H.sub.9 212-2141250 i-C.sub.3 H.sub.7 2,4-Cl.sub.2C.sub.6 H.sub.3 tert.-C.sub.4 H.sub.9 140-1411251 i-C.sub.3 H.sub.7 cyclooctanimino tert.-C.sub.4 H.sub.9 oil, 1.37(d, 6H), 1.47(s; 9H), 1.28-1.93(m; 10H), 2.54(m; 4H), 3.44(sept, 1H), 8.44(bs; 1H, NH)1252 i-C.sub.3 H.sub.7 (CH.sub.2).sub.2 O(CH.sub.2).sub.2 OCH.sub.3 tert.-C.sub.4 H.sub.9 oil, 1.34(d; 6H), 1.47(s; 9H), 3.39(s; 3H), 3.45(sept; 1H), 3.60(m; 4H), 3.84 and 4.50(m; 4H), 8.94(bs; 1H, NH)1253 i-C.sub.3 H.sub.7 CH.sub.2CH.sub.2SCH.sub.3 tert.-C.sub.4 H.sub.9 46-481254 i-C.sub.3 H.sub.7 Pyrid-2-yl tert.-C.sub.4 H.sub.9 155-1631255 i-C.sub.3 H.sub.7 CH.sub.2CH.sub.2Cl tert.-C.sub.4 H.sub.9 70-721263 n-C.sub.4 H.sub.9 H CH.sub.3 146-1491264 n-C.sub.4 H.sub.9 H i-C.sub.3 H.sub.7 60-631265 n-C.sub.4 H.sub.9 H cyclo-C.sub.3 H.sub.5 112-1141266 n-C.sub.4 H.sub.9 H C.sub.6 H.sub.5 145-1501267 n-C.sub.4 H.sub.9 H tert.-C.sub.4 H.sub.9 52-541268 n-C.sub.4 H.sub.9 NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.9 58-621269 n-C.sub.4 H.sub.9 CH.sub.2 CCl.sub.3 tert.-C.sub.4 H.sub.9 oil 0.92(t; 3H), 1.43(m, 2H), 1.48(s; 9H), 1.74(m; 2H) 3.00(t; 2H), 5.01(s; 2H), 8.80(bs; 1H; NH)1270 n-C.sub.4 H.sub.9 2,6-Br.sub.2 -4-CNC.sub.6 H.sub.2 tert.-C.sub.4 H.sub.9 165-1701271 n-C.sub.4 H.sub.9 CH.sub.2CHCH.sub.2 tert.-C.sub.4 H.sub.9 oil 0.92(t; 3H), 1.41(m; 2H), 1.46(s; 9H), 1.66(m; 2H), 2.89(t; 2H), 4.88(d; 2H), 5.40(m; 2H), 6.01(m; 1H), 9.19(bs; 1H, NH)1272 n-C.sub.4 H.sub.9 2,4-dichlorobenzyl tert.-C.sub.4 H.sub.9 81-861273 n-C.sub.4 H.sub.9 H cyclopropylmethyl 65-701274 s-C.sub.4 H.sub.9 H i-C.sub.3 H.sub.7 oil 0.92(t, 3H), 1.34(d, 3H), 1.39(d; 6H), 1.76(m; 2H), 3.65(m; 1H), 4.32(m; 1H), 7.08(bs; 1H, NH)1275 s-C.sub.4 H.sub.9 NC(CH.sub.3).sub.2 i-C.sub.3 H.sub.7 80-841276 s-C.sub.4 H.sub.9 H cyclo-C.sub.3 H.sub.7 78-851277 s-C.sub.4 H.sub.9 NC(CH.sub.3).sub.2 cyclo-C.sub.3 H.sub.5 oil 0.70(m,; 2H), 0.90(m; 2H), 0.92(t; 3H), 1.34(d; 3H), 1.79(m; 2H), 2.14 and 2.18(2s; 6H), 2.97(m; 1H), 3.24(m; 1H), 8.80(bs, 1H, NH)1278 s-C.sub.4 H.sub.9 succinimido cyclo-C.sub.3 H.sub.5 112-1151279 s-C.sub.4 H.sub.9 H tert.-C.sub.4 H.sub.9 93-951280 s-C.sub.4 H.sub.9 NC(CH.sub.3).sub.2 tert.-C.sub. 4 H.sub.9 oil 0.92(t, 3H), 1.34(d; 3H), 1.48(s; 9H), 1.80(m; 2H), 2.12 and 2.16(2s; 6H), 3.26(m, 1H), 8.29(bs, 1H, NH)1281 s-C.sub.4 H.sub.9 H C.sub.6 H.sub.5 117-1201282 s-C.sub.4 H.sub.9 NC(CH.sub.3).sub.2 C.sub.6 H.sub.5 oil, 0.93(t; 3H), 1.36(d; 3H), 1.80(m; 2H), 2.14 and 2.18(2s; 6H), 3.28(m; 1H), 7.10-7.80(m; 5H) 10.90(bs; 1H), NH)1283 tert.-C.sub.4 H.sub.9 succinimido i-C.sub.3 H.sub.7 137-1401284 tert.-C.sub.4 H.sub.9 succinimido 4-ClC.sub.6 H.sub.4 238-2421285 tert.-C.sub.4 H.sub.9 succinimido tert.-C.sub.4 H.sub.9 144-1461286 tert.-C.sub.4 H.sub.9 NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.9 86-901287 tert.-C.sub.4 H.sub.9 H cyclo-C.sub.3 H.sub.5 75-771288 tert.-C.sub.4 H.sub.9 NC(CH.sub.3).sub.2 cyclo-C.sub.3 H.sub.5 93-981290 neo-C.sub.5 H.sub.11 H CH.sub.3 130-1331291 neo-C.sub.5 H.sub.11 H i-C.sub.3 H.sub.7 100-1041292 neo-C.sub.5 H.sub.11 H cyclo-C.sub.3 H.sub.5 133-1361293 neo-C.sub.5 H.sub.11 NC(CH.sub.3).sub.2 cyclo-C.sub.3 H.sub.5 56-621294 neo-C.sub.5 H.sub.11 H tert.-C.sub.4 H.sub.9 112-1171295 neo-C.sub.5 H.sub.11 NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.9 107-1111296 neo-C.sub.5 H.sub.11 H C.sub.6 H.sub.5 205-2071297 cyclo-C.sub.3 H.sub.5 succinimido i-C.sub.3 H.sub.7 131-1331298 cyclo-C.sub.3 H.sub.5 succinimido tert.-C.sub.4 H.sub.9 167-1681299 cyclo-C.sub.3 H.sub.5 succinimido C.sub.6 H.sub.5 168-1701300 cyclo-C.sub.3 H.sub.5 H cyclo-C.sub.3 H.sub.5 139-1401301 cyclo-C.sub.3 H.sub.5 NC(CH.sub.3).sub.2 cyclo-C.sub.3 H.sub.5 oil 0.80(m; 8H), 2.02 and 2.04(2s; 6H), 2.30(m; 1H), 2.86(m; 1H), 9.20(d; 1H, NH)1302 cyclo-C.sub.3 H.sub.5 NC(cyclo- cyclo-C.sub.3 H.sub.7 106-108 C.sub.3 H.sub.5).sub.21303 cyclo-C.sub.3 H.sub.5 H cyclo-C.sub.5 H.sub.9 106-1091304 cyclo-C.sub.3 H.sub.5 NC(CH.sub.3).sub.2 cyclo-C.sub.5 H.sub.9 125-1271305 cyclo-C.sub.5 H.sub.9 H C.sub.6 H.sub.5 170-1711306 cyclo-C.sub.5 H.sub.9 H cyclo-C.sub.3 H.sub.5 118-1201307 cyclo-C.sub.5 H.sub.9 NC(CH.sub.3 ).sub.2 cyclo-C.sub.3 H.sub.5 55-571308 cyclo-C.sub.5 H.sub.9 NC(CH.sub.3).sub.2 CH.sub.3 100-1011309 cyclo-C.sub.5 H.sub.9 H CH.sub.3 166-1671310 cyclo-C.sub.5 H.sub.9 H tert.-C.sub.4 H.sub.9 125-1261311 cyclo-C.sub.5 H.sub.9 NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.9 112-1141312 tetrahydro- succinimido C.sub.6 H.sub.5 80 pyran-3-yl1313 2-CH.sub.3 OC.sub.6 H.sub.4 H tert.-C.sub.4 H.sub.9 179-1841314 2-CH.sub.3 OC.sub.6 H.sub.4 H cyclo-C.sub.4 H.sub.5 177-1801315 2,6F.sub.2C.sub.6 H.sub.3 H tert.-C.sub.4 H.sub.9 128-1351316 2,6F.sub.2C.sub.6 H.sub.3 H cyclo-C.sub.3 H.sub.5 134-1381317 CH.sub.3O H tert.-C.sub.4 H.sub.9 oil 1.52(s; 9H), 4.12(s; 3H), 7.16(bs; 1H, NH)1318 CH.sub.3OCH.sub.2 H tert.-C.sub.4 H.sub.9 95-1001319 CH.sub.3OCH.sub.2 H cyclo-C.sub.3 H.sub.5 90-951320 CH.sub.3OCH.sub.2 NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.9 65-701321 CH.sub.3OCH(CH.sub.3) NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.9 oil 1.45(s; 9H) 1.60(d; 3H), 2.16 and 2.18(2s; 6H); 3.34(s; 3H), 4.87(quart.; 1H) 8.10(bs; 1H, NH)1322 CH.sub.3OCH(CH.sub.3) H tert.-C.sub.4 H.sub.9 69-711323 CH.sub.3OCH(CH.sub.3) 2,6-Br.sub.2 -4-CNC.sub.6 H.sub.2 tert.-C.sub.4 H.sub.9 118-1201324 CH.sub.3 CH(CH.sub.3)CO.sub.2 CH.sub.3 tert.-C.sub.4 H.sub.9 oil 1.46(s; 9H) 2.54(s; 3H) 3.82(s; 3H), 5.40(quart.; 1H) 9.00(bs, 1H, NH)1325 CH.sub.3 2,6-Br.sub.2 -4-CNC.sub.6 H.sub.2 tert.-C.sub.4 H.sub.9 143-1461326 ##STR42## H tert.-C.sub.4 H.sub.9 168-1701327 ##STR43## H tert.-C.sub.4 H.sub.9 1571328 ##STR44## H tert.-C.sub.4 H.sub.9 2541329 ##STR45## CH.sub.3 tert.-C.sub.4 H.sub.9 oil 1.5(s, 9H) 3.8; (s; 3H), 3.9(s; 3H), 6.5(d; 1H), 7.6(d; 1H), 8.7(bs, 1H, NH)1330 ##STR46## CH.sub.3 tert.-C.sub.4 H.sub.9 120-122.degree. C.1331 ##STR47## CH.sub.3 tert.-C.sub.4 H.sub.9 oil, 1.5(s; 9H), 3.7(s; 3H), 3.8(s; 3H), 3.9(s, 3H), 8.0(s; 1H), 9.2(bs, 1H, NH)1332 ##STR48## H tert.-C.sub.4 H.sub.91333 ##STR49## NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.91334 ##STR50## H tert.-C.sub.4 H.sub.91335 ##STR51## NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.91336 pyrid-2-yl H tert.-C.sub.4 H.sub.91337 pyrid-2-yl NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.91338 pyrid-3-yl H tert.-C.sub.4 H.sub.91339 pyrid-3-yl NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.91340 pyrid-4-yl H tert.-C.sub.4 H.sub.91341 pyrid-4-yl NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.91342 4-FC.sub.6 H.sub.4CH.sub.2 H tert.-C.sub.4 H.sub.91343 4-FC.sub.6 H.sub.4CH.sub.2 NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.91344 CH.sub.3 n-C.sub.4 H.sub.9 tert.-C.sub.4 H.sub.91345 CH.sub.3 C.sub.6 H.sub.5 tert.-C.sub.4 H.sub.91346 CH.sub.3 tert.-C.sub.4 H.sub.9 tert.-C.sub.4 H.sub.91347 C.sub.2 H.sub.5 n-C.sub.4 H.sub.9 tert.-C.sub.4 H.sub.91348 C.sub.2 H.sub.5 C.sub.6 H.sub.5 tert.-C.sub.4 H.sub.91349 i-C.sub.3 H.sub.7 n-C.sub.4 H.sub.9 tert.-C.sub.4 H.sub.91350 i-C.sub.3 H.sub.7 C.sub.6 H.sub.51351 i-C.sub.3 H.sub.7 cyclopentanimino tert.-C.sub.4 H.sub.9 113-115__________________________________________________________________________
TABLE 2______________________________________ ##STR52## mp [.degree.C.]/.sup.1 H-NMRNo. R.sup.1 R.sup.5 R.sup.4 (CDCl.sub.3) [ppm]______________________________________2001 CH.sub.3 n-C.sub.4 H.sub.9 tert.-C.sub.4 H.sub.92002 CH.sub.3 C.sub.6 H.sub.5 tert.-C.sub.4 H.sub.92003 CH.sub.3 tert.-C.sub.4 H.sub.9 tert.-C.sub.4 H.sub.9 oil; 1.46(s; 9H) 1.60(s; 9H), 2.50(s; 3H), 7.94(bs; 1H, NH)2004 C.sub.2 H.sub.5 n-C.sub.4 H.sub.9 tert.-C.sub.4 H.sub.92005 C.sub.2 H.sub.5 C.sub.6 H.sub.5 tert.-C.sub.4 H.sub.92006 i-C.sub.3 H.sub.7 C.sub.6 H.sub.5 tert.-C.sub.4 H.sub.92007 i-C.sub.3 H.sub.7 n-C.sub.4 H.sub.9 tert.-C.sub.4 H.sub.9______________________________________
TABLE 3__________________________________________________________________________ ##STR53## mp [.degree.C.]/H-NMRNo. R.sup.1 R.sup.5 R.sup.4 (CDCl.sub.3) [ppm]__________________________________________________________________________3001 CH.sub.3 H i-C.sub.3 H.sub.7 153-1543002 CH.sub.3 H tert.-C.sub.4 H.sub.9 158-1593003 CH.sub.3 H C.sub.6 H.sub.5 178-1833004 CH.sub.3 H 4-ClC.sub.6 H.sub.4 2313005 CH.sub.3 H 3-CF.sub.3C.sub.6 H.sub.4 221-2233006 C.sub.2 H.sub.5 H i-C.sub.3 H.sub.7 138-1403007 C.sub.2 H.sub.5 CH.sub.3 i-C.sub.3 H.sub.7 55-563008 C.sub.2 H.sub.5 H tert.-C.sub.4 H.sub.9 155-1573009 C.sub.2 H.sub.5 CH.sub.3 tert.-C.sub.4 H.sub.9 393010 C.sub.2 H.sub.5 H C.sub.6 H.sub.5 1643011 C.sub.2 H.sub.5 CH.sub.3 C.sub.6 H.sub.5 130-1313012 C.sub.2 H.sub.5 H 4-ClC.sub.6 H.sub.4 202-2043013 C.sub.2 H.sub.5 CH.sub.3 4-ClC.sub.6 H.sub.4 158-1593014 C.sub.2 H.sub.5 H 3-CF.sub.3C.sub.6 H.sub.4 191-1953015 C.sub.2 H.sub.5 CH.sub.3 3-CF.sub.3C.sub.6 H.sub.4 843016 i-C.sub.3 H.sub.7 H i-C.sub.3 H.sub.7 160-1623017 i-C.sub.3 H.sub.7 CH.sub.3 i-C.sub.3 H.sub.7 90-913018 i-C.sub.3 H.sub.7 H tert.-C.sub.4 H.sub.9 178-1793019 i-C.sub.3 H.sub.7 CH.sub.3 tert.-C.sub.4 H.sub.9 38-413020 i-C.sub.3 H.sub.7 H C.sub.6 H.sub.5 171-1723021 i-C.sub.3 H.sub.7 CH.sub.3 C.sub.6 H.sub.5 92-933022 i-C.sub.3 H.sub.7 H 4-ClC.sub.6 H.sub.4 185-1863023 i-C.sub.3 H.sub.7 CH.sub.3 4-ClC.sub.6 H.sub.4 92-933024 i-C.sub.3 H.sub.7 H 3-CF.sub.3C.sub.6 H.sub.4 177-1793025 i-C.sub.3 H.sub.7 CH.sub.3 3-CF.sub.3C.sub.6 H.sub.4 37-453026 C.sub.6 H.sub.5 H i-C.sub.3 H.sub.7 1443027 C.sub.6 H.sub.5 CH.sub.3 i-C.sub.3 H.sub.7 98- 1003028 C.sub.6 H.sub.5 H tert.-C.sub.4 H.sub.9 2093029 C.sub.6 H.sub.5 CH.sub.3 tert.-C.sub.4 H.sub.9 130-1313030 C.sub.6 H.sub.5 H C.sub.6 H.sub.5 2043031 C.sub.6 H.sub.5 CH.sub.3 C.sub.6 H.sub.5 100-1013032 C.sub.6 H.sub.5 H 4-ClC.sub.6 H.sub.4 2093033 C.sub.6 H.sub.5 CH.sub.3 4-ClC.sub.6 H.sub.4 157-1583034 C.sub.6 H.sub.5 H 3-CF.sub.3C.sub.6 H.sub.4 2173035 C.sub.6 H.sub.5 CH.sub.3 3-CF.sub.3C.sub.6 H.sub.4 131-1323036 i-C.sub.3 H.sub.7 succinimido i-C.sub.3 H.sub.7 98-1003037 i-C.sub.3 H.sub.7 succinimido tert.-C.sub.4 H.sub.9 75-763038 i-C.sub.3 H.sub.7 Na.sup..sym. tert.-C.sub.4 H.sub.9 3003039 i-C.sub.3 H.sub.7 K.sup..sym. tert.-C.sub.4 H.sub.9 1103040 i-C.sub.3 H.sub.7 Na.sup..sym. C.sub.6 H.sub.5 3303041 i-C.sub.3 H.sub.7 K.sup..sym. C.sub.6 H.sub.5 3003042 i-C.sub.3 H.sub.7 ##STR54## C.sub.6 H.sub. 5 154-1573043 i-C.sub.3 H.sub.7 ##STR55## C.sub.6 H.sub.5 162-1643044 i-C.sub.3 H.sub.7 succinimido C.sub.6 H.sub.5 1613045 CH.sub.3 NC(CH.sub.3).sub.2 tert.-C.sub.4 H.sub.9 97-98__________________________________________________________________________
Other compounds, for instance, having the general structure ##STR56## may be prepared analogously in which X and Y are oxygen or sulfur, e.g., R.sup.1 is a radical from the group Q1 to Q61,
R.sup.5 is a radical from the group M1 to M78,
R.sup.3 is a radical from the group P.sub.1 -P.sub.11
R.sup.4 is a radical from the group L1 to L195, and
the radicals X, Y, P, Q, M and L may be combined at will.
R.sup.1, R.sup.5, R.sup.3 and R.sup.4 may for example denote the following radicals:
______________________________________CompNo. R.sup.1______________________________________Q1 HQ2 CH.sub.3Q3 C.sub.2 H.sub.5Q4 n-C.sub.3 H.sub.7Q5 i-C.sub.3 H.sub.7Q6 n-C.sub.4 H.sub.9Q7 i-C.sub.4 H.sub.9Q8 s-C.sub.4 H.sub.9Q9 tert.-C.sub.4 H.sub.9Q10 cyclo-C.sub.3 H.sub.5Q11 cyclo-C.sub.4 H.sub.7Q12 cyclo-C.sub.5 H.sub.9Q13 cyclo-C.sub.6 H.sub.11Q14 cyclo-C.sub.7 H.sub.13Q15 cyclo-C.sub.8 H.sub.15Q16 CF.sub.3Q17 CH.sub.2 OCH.sub.3Q18 CH(CH.sub.3)OCH.sub.3Q19 CH(CH.sub.3)CH.sub.2 OCH.sub.3Q20 CH.sub.2 OC.sub.2 H.sub.5Q21 tetrahydrofur-2-ylQ22 tetrahydrofur-2-ylQ23 tetrahydrofur-2-ylQ24 tetrahydropyran-3-ylQ25 tetrahydropyran-3-ylQ26 C.sub.6 H.sub.5Q27 2-FC.sub.6 H.sub.4Q28 3-FC.sub.6 H.sub.4Q29 4-FC.sub.6 H.sub.4Q30 2-ClC.sub.6 H.sub.4Q31 3-ClC.sub.6 H.sub.4Q32 4-ClC.sub.6 H.sub.4Q33 2-CH.sub.3C.sub.6 H.sub.4Q34 3-CH.sub.3C.sub.6 H.sub.4Q35 4-CH.sub.3C.sub.6 H.sub.4Q36 2-CF.sub.3C.sub.6 H.sub.4Q37 3-CF.sub.3C.sub.6 H.sub.4Q38 4-CF.sub.3C.sub.6 H.sub.4Q39 2-OCH.sub.3C.sub.6 H.sub.4Q40 3-OCH.sub.3C.sub.6 H.sub.4Q41 4-OCH.sub.3C.sub.6 H.sub.4Q42 4-OCF.sub.3C.sub.6 H.sub.4Q43 4-SCH.sub.3C.sub.6 H.sub.4Q44 4-SCF.sub.3C.sub.6 H.sub.4Q45 4-NO.sub.2C.sub.6 H.sub.4Q46 4-CNC.sub.6 H.sub.4Q47 neo-C.sub.5 H.sub.11Q48 CH.sub.3 OQ49 C.sub.2 H.sub.5 OQ50 C.sub.6 H.sub.5CH.sub.2Q51 4-FC.sub.6 H.sub.4CH.sub.2Q51 4-CH.sub.3C.sub.6 H.sub.4CH.sub.2Q52 ##STR57##Q53 ##STR58##Q54 ##STR59##Q55 ##STR60##Q56 ##STR61##Q57 ##STR62##Q58 ##STR63##Q59 pyrid-2-ylQ60 pyrid-3-ylQ61 pyrid-4-ylQ62 2,6-F.sub.2C.sub.6 H.sub.3______________________________________Comp.No. R.sup.5______________________________________M1 HM2 CH.sub.3M3 C.sub.2 H.sub.5M4 n-C.sub.3 H.sub.7M5 i-C.sub.3 H.sub.7M6 n-C.sub.4 H.sub.9M7 s-C.sub.4 H.sub.9M8 t-C.sub.4 H.sub.9M9 CH(CH.sub.3)C.sub.6 H.sub.13M10 CH.sub.2 CH.sub.2 OCH.sub.3M11 CH.sub.2 CH.sub.2 OC.sub.2 H.sub.5M12 succinimidoM13 Li.sup..sym.M14 Na.sup..sym.M15 K.sup..sym.M16 NH.sub.4.sup..sym.M17 H.sub.3 N.sup..sym. i-C.sub.3 H.sub.7M18 H.sub.2 N.sup..sym. (i-C.sub.3 H.sub.7).sub.2M19 H.sub.3 N.sup..sym. CH.sub.2 CH.sub.2 OHM20 CH.sub.2 CHCH.sub.2M21 CH.sub.2C(CH.sub.3)CH.sub.2M22 CH.sub.2C(Cl)CH.sub.2M23 CH.sub.2CCHM24 CH.sub.2C CCH.sub.2 OHM25 NC(CH.sub.3).sub.2M26 NC(C.sub.2 H.sub.5).sub.2M27 CH.sub.2CH.sub.2N(CH.sub.3).sub.2M28 CH.sub.2CH.sub.2N(C.sub.2 H.sub.5).sub.2M29 CH.sub.2CH.sub.2 N.sup..sym. (CH.sub.3).sub.3 I.sup..crclbar .M30 CH.sub.2CF.sub.3M31 phenylM32 phenylethylM33 CH.sub.2CH.sub.2Si(CH.sub.3).sub.3M34 CH.sub.2CH.sub.2ONC(CH.sub.3).sub.2M35 CH.sub.2PO(OC.sub.2 H.sub.5).sub.2M36 CH(CH.sub.3)CH(OCH.sub.3).sub.2M37 CH.sub.2CON(C.sub.2 H.sub.5).sub.2M38 N(C.sub.2 H.sub.5).sub.2M39 CH.sub.OCH.sub.2C.sub.6 H.sub.5M40 CH(COOCH.sub.3).sub.2M41 NC(cyclo-C.sub.3 H.sub.5).sub.2M42 ##STR64##M43 cyclohexaniminoM44 cyclooctaniminoM45 CH.sub.2CH.sub.2ClM46 CH.sub.2CH.sub.2CNM47 CH.sub.2CCl.sub.3M48 pyrid-3-ylmethylM49 thien-2-yl-methylM50 ##STR65##M51 ##STR66##M52 ##STR67##M53 CH(C.sub.6 H.sub.5)COOCH.sub.3M54 cyclo-C.sub.6 H.sub.11M55 CH.sub.2OCH.sub.2C.sub.6 H.sub.5M56 tetrahydropyran-2-ylM57 tetrahydrofur-2-ylM58 (4-bromobenzoyl)methylM59 (4-methoxybenzoyl)methylM60 CH(COOCH.sub.3).sub.2M61 phthalimidomethylM62 fur-2-ylmethylM63 tetrahydrofur-2-yl-methylM64 pyrid-2-ylmethylM65 pyrid-4-ylmethylM66 pyrid-3-yl-methylM67 thien-2-yl-methylM68 CH(C.sub.6 H.sub.5)COOCH.sub.3M69 piperidinoM70 phthalimidoM71 ##STR68##M72 NCHC.sub.6 H.sub.5M73 ##STR69##M74 2-NO.sub.2 -4-FC.sub.6 H.sub.3M75 3,5-(CF.sub.3).sub.2C.sub.6 H.sub.3M76 CH.sub.2CH.sub.2SCH.sub.3M77 4-NHCOCH.sub.3C.sub.6 H.sub.4M78 2,4-dichlorobenzyl______________________________________Comp.No. R.sup.3______________________________________P1 HP2 CH.sub.3P3 C.sub.2 H.sub.5P4 n-C.sub.3 H.sub.7P5 i-C.sub.3 H.sub.7P6 n-C.sub.4 H.sub.9P7 s-C.sub.4 H.sub.9P8 t-C.sub.4 H.sub.9P9 CH.sub.2CH.sub.2 OHP10 CH.sub.2CH.sub.2 ClP11 CH.sub.2 OCH.sub.3P12 CH.sub.2 OC.sub.2 H.sub.5P13 CH.sub.2 CH.sub.2 OCH.sub.3P14 CH.sub.2 SCH.sub.3P15 CH.sub.2 SC.sub.2 H.sub.5P16 CH.sub.2 CH.sub.2 SCH.sub.3P17 CH.sub.2CH.sub.2N(CH.sub.3).sub.2P18 CH.sub.2 CH.sub.2N(C.sub.2 H.sub.5).sub.2P19 cyclo-C.sub.3 H.sub.5P20 cyclo-C.sub.6 H.sub.11P21 1-methyl-cyclo-C.sub.6 H.sub.10______________________________________Comp.No. R.sup.4______________________________________L1 HL2 CH.sub.3L3 C.sub.2 H.sub.5L4 n-C.sub.3 H.sub.7L5 i-C.sub.3 H.sub.6L6 n-C.sub.4 H.sub.9L7 i-C.sub.4 H.sub.9L8 sec-C.sub.4 H.sub.9L9 tert.-C.sub.4 H.sub.9L10 n-C.sub.5 H.sub.11L11 CH(CH.sub.3)C.sub.3 H.sub.6L12 CH(C.sub.2 H.sub.5)C.sub.2 H.sub.5L13 n-C.sub.6 H.sub.13L14 CH(CH.sub.3)C.sub.4 H.sub.9L15 CH(C.sub.2 H.sub.5)C.sub.3 H.sub.7L16 n-C.sub.7 H.sub.15L17 CH(CH.sub.3)C.sub.5 H.sub.11L18 CH(C.sub.2 H.sub.5)C.sub.4 H.sub.9L19 n-C.sub.8 H.sub.17L20 CH(CH.sub.3)C.sub.6 H.sub.13L21 CH(C.sub.2 H.sub.5)C.sub.5 H.sub.11L22 C(CH.sub.3).sub.2 CH.sub.2 C(CH.sub.3).sub.3L23 cyclo-C.sub.3 H.sub.5L24 cyclo-C.sub.4 H.sub.7L25 cyclo-C.sub.5 H.sub.9L26 cyclo-C.sub.6 H.sub.11L27 cyclo-C.sub.7 H.sub.13L28 cyclo-C.sub.8 H.sub.15L29 1-methylcyclohexylL30 1-ethylcyclohexylL31 3,5-dimethylcyclohexylL32 3-trifluoromethylcyclohexylL33 tetrahydropyran-4-ylL34 4-methyl-tetrahydropyranL35 4-methyl-tetrahydropyran-4-ylL36 CH.sub.2CHCH.sub.2L37 CH(CH.sub.3)CHCH.sub.2L38 C(CH.sub.3).sub.2 CHCH.sub.2L39 C(CH.sub.3,C.sub.2 H.sub.5)CHCH.sub.2L40 C(CH.sub.3).sub.2C.sub.2 H.sub.5L41 C(CH.sub.3,C.sub.2 H.sub.5)C.sub.2 H.sub.5L42 C(CH.sub.3).sub.2 C.sub.3 H.sub.7L43 C(CH.sub.3).sub.2 cycloC.sub.6 H.sub.11L44 CH.sub.2 C(CH.sub.3)CH.sub.2L45 CH.sub.2 CHCHCH.sub.3L46 CH(CH.sub.3)CHCHCH.sub.3L47 C(CH.sub.3).sub.2 CHCHCH.sub.3L48 CH.sub.2 CCHL49 CH(CH.sub.3)CCHL50 C(CH.sub.3).sub.2 CCHL51 C(CH.sub.3,C.sub.2 H.sub.5)CCHL52 C(C.sub.2 H.sub.5).sub.2 CCHL53 CH.sub.2 CCCH.sub.3L54 CH(CH.sub.3)CCCH.sub.3L55 C(CH.sub.3).sub.2 CCCH.sub.3L56 CH.sub.2 C.sub.6 H.sub.5L57 CH(CH.sub.3)C.sub.6 H.sub.5L58 C(CH.sub.3).sub.2 C.sub.6 H.sub.5L59 CH.sub.2 CH.sub.2 C.sub.6 H.sub.5L60 CH.sub.2 CH.sub.2 SCH.sub.3L61 CH(CH.sub.3)CH.sub.2 SCH.sub.3L62 C(CH.sub.3).sub.2 CH.sub.2 SCH.sub.3L63 CH.sub.2 CH.sub.2 CH.sub.2 SCH.sub.3L64 CH.sub.2 CH.sub.2 ClL65 CH(CH.sub.3)CH.sub.2 ClL66 C(CH.sub.3).sub.2 CH.sub.2 ClL67 CH.sub.2 CH.sub.2 OCH.sub.3L68 CH(CH.sub.3)CH.sub.2 OCH.sub.3L69 C(CH.sub.3).sub.2 CH.sub.2 OCH.sub.3L70 CH.sub.2 CH.sub.2 N(CH.sub.3).sub.2L71 CH.sub.2 CH.sub.2 N(C.sub.2 H.sub.5).sub.2L72 CH.sub.2 CH.sub.2 CH.sub.2 OCH.sub.3L73 CH.sub.2 CH.sub.2 CH.sub.2 N(CH.sub.3).sub.2L74 CH.sub.2 CH.sub.2 CH.sub.2 N(C.sub.2 H.sub.5).sub.2L75 2-CH.sub.3C.sub.6 H.sub.4L76 3-CH.sub.3C.sub.6 H.sub.4L77 4-CH.sub.3C.sub.6 H.sub.4L78 2-C.sub.2 H.sub.5C.sub.6 H.sub.4L79 3-C.sub.2 H.sub.5C.sub.6 H.sub.4L80 4-C.sub.2 H.sub.5C.sub.6 H.sub.4L81 3-tert.-C.sub.4 H.sub.9C.sub.6 H.sub.4L82 4-tert.-C.sub.4 H.sub.9C.sub.6 H.sub.4L83 2,3-(CH.sub.3).sub.2C.sub.6 H.sub.3L84 2,4-(CH.sub.3).sub.2C.sub.6 H.sub.3L85 2,5-(CH.sub.3).sub.2C.sub.6 H.sub.3L86 2,6-(CH.sub.3).sub.2C.sub.6 H.sub.3L87 3,4-(CH.sub.3).sub.2C.sub.6 H.sub.3L88 3,5-(CH.sub.3).sub.2C.sub.6 H.sub.3L89 2,3,4-(CH.sub.3).sub.3C.sub.6 H.sub.2L90 2,3,5-(CH.sub.3).sub.3C.sub.6 H.sub.2L91 2,4,5-(CH.sub.3).sub.3C.sub.6 H.sub.2L92 2,4,6-(CH.sub.3).sub.3C.sub.6 H.sub.2L93 3,4,5-(CH.sub.3).sub.3C.sub.6 H.sub.2L94 2-CF.sub.3C.sub.6 H.sub.4L95 3-CF.sub.3C.sub.6 H.sub.4L96 4-CF.sub.3C.sub.6 H.sub.4L97 2-FC.sub.6 H.sub.4L98 3-FC.sub.6 H.sub.4L99 4-FC.sub.6 H.sub.4L100 2-ClC.sub.6 H.sub.4L101 3-ClC.sub.6 H.sub.4L102 4-ClC.sub.6 H.sub.4L103 2-BrC.sub.6 H.sub.4L104 3-BrC.sub.6 H.sub.4L105 4-BrC.sub.6 H.sub.4L106 2,3-F.sub.2C.sub.6 H.sub.3L107 2,4-F.sub.2C.sub.6 H.sub.3L108 2,5-F.sub.2C.sub. 6 H.sub.3L109 2,6-F.sub.2C.sub.6 H.sub.3L110 2,3-Cl.sub.2C.sub.6 H.sub.3L111 2,4-Cl.sub.2C.sub.6 H.sub.3L112 2,5-Cl.sub.2C.sub.6 H.sub.3L113 2,6-Cl.sub.2C.sub.6 H.sub.3L114 3,4-Cl.sub.2C.sub.6 H.sub.3L115 3,5-Cl.sub.2C.sub.6 H.sub.3L116 2,3,4-Cl.sub.3C.sub.6 H.sub.2L117 2,3,5-Cl.sub.3C.sub.6 H.sub.2L118 2,4,6-Cl.sub.3C.sub.6 H.sub.2L119 3,4,5-Cl.sub.3C.sub.6 H.sub.2L120 2-CNC.sub.6 H.sub.4L121 3-CNC.sub.6 H.sub.4L122 4-CNC.sub.6 H.sub.4L123 2-OCH.sub.3C.sub.6 H.sub.4L124 3-OCH.sub.3C.sub.6 H.sub.4L125 4-OCH.sub.3C.sub.6 H.sub.4L126 2-OC.sub.2 H.sub.5C.sub.6 H.sub.4L127 3-OC.sub.2 H.sub.5C.sub.6 H.sub.4L128 4-OC.sub.2 H.sub.5C.sub.6 H.sub.4L129 2-O-n-C.sub.3 H.sub.7C.sub.6 H.sub.4L130 3-O-n-C.sub.3 H.sub.7C.sub.6 H.sub.4L131 4-O-n-C.sub.3 H.sub.7C.sub.6 H.sub.4L132 2-O-i-C.sub.3 H.sub.7C.sub.6 H.sub.4L133 3-O-i-C.sub.3 H.sub.7C.sub.6 H.sub.4L134 4-O-i-C.sub.3 H.sub.7C.sub.6 H.sub.4L135 2,3-(OCH.sub.3).sub.2C.sub.6 H.sub.3L136 2,4-(OCH.sub.3).sub.2C.sub.6 H.sub.3L137 2,5-(OCH.sub.3).sub.2C.sub.6 H.sub.3L138 2,6-(OCH.sub.3).sub.2C.sub.6 H.sub.3L139 3,4-(OCH.sub.3).sub.2C.sub.6 H.sub.3L140 3,5-(OCH.sub.3).sub.2C.sub.6 H.sub.3L141 3,4,5-(OCH.sub.3).sub.3C.sub.6 H.sub.2L142 2-OCF.sub.3C.sub.6 H.sub.4L143 3-OCF.sub.3C.sub.6 H.sub.4L144 4-OCF.sub.3C.sub.6 H.sub.4L145 2-OCF.sub.2 CHF.sub.2C.sub.6 H.sub.4L146 3-OCF.sub.2 CHF.sub.2C.sub.6 H.sub.4L147 4-OCF.sub.2 CHF.sub.2C.sub.6 H.sub.4L148 2-SCH.sub.3C.sub.6 H.sub.4L149 3-SCH.sub.3C.sub.6 H.sub.4L150 4-SCH.sub.3C.sub.6 H.sub.4L151 2-SC.sub.2 H.sub.5C.sub.6 H.sub.4L152 3-SC.sub.2 H.sub.5C.sub.6 H.sub.4L153 4-SC.sub.2 H.sub.5C.sub.6 H.sub.4L154 2-S-i-C.sub.3 H.sub.7C.sub.6 H.sub.4L155 3-S-i-C.sub.3 H.sub.7C.sub.6 H.sub.4L156 4-S-i-C.sub.3 H.sub.7C.sub.6 H.sub.4L157 2,4-(SCH.sub.3).sub.2C.sub.6 H.sub.3L158 2-SCF.sub.3C.sub.6 H.sub.4L159 3-SCF.sub.3C.sub.6 H.sub.4L160 4-SCF.sub.3C.sub.6 H.sub.4L161 2-NO.sub.2C.sub.6 H.sub.4L162 3-NO.sub.2C.sub.6 H.sub.4L163 4-NO.sub.2C.sub.6 H.sub.4L164 2,3-(NO.sub.2).sub.2C.sub.6 H.sub.3L165 2,4-(NO.sub.2).sub.2C.sub.6 H.sub.3L166 2,5-(NO.sub.2).sub.2C.sub.6 H.sub.3L167 2,6-(NO.sub.2).sub.2C.sub.6 H.sub.3L168 3,4-(NO.sub.2).sub.2C.sub.6 H.sub.3L169 3,5-(NO.sub.2).sub.2C.sub.6 H.sub.3L170 2-CHOC.sub.6 H.sub.4L171 3-CHOC.sub.6 H.sub.4L172 4-CHOC.sub.6 H.sub.4L173 ##STR70##L174 ##STR71##L175 ##STR72##L176 ##STR73##L177 ##STR74##L178 ##STR75##L179 ##STR76##L180 ##STR77##L181 ##STR78##L182 ##STR79##L183 ##STR80##L184 ##STR81##L185 1-naphthylL186 2-naphthylL187 C.sub.6 H.sub.5L188 piperidinoL189 tetrahydrofur-3-ylL190 thiazol-2-ylL191 5-methyl-thiazol-2-ylL192 5-ethyl-thiazol-2-ylL193 5-n-propyl-thiazol-2-ylL194 4-methyl-5-carboxy-thiazol-2-ylL195 cyclopropylmethyl______________________________________
The compounds Ia, or the herbicidal agents containing them, may be applied for instance in the form of directly sprayable solutions, powders, suspension (including high-percentage aqueous, oily or other suspensions), dispersions, emulsions, oil dispersions, pastes, dusts, broadcasting agents, or granules by spraying, atomizing, dusting, broadcasting or watering. The forms of application depend entirely on the purpose for which the agents are being used, but they must ensure as fine a distribution of the active ingredients according to the invention as possible.
For the preparation of solutions, emulsions, pastes and oil dispersions to be sprayed direct, mineral oil fractions of medium to high boiling point, such as kerosene or diesel oil, further coal-tar oils, and oils of vegetable or animal origin, aliphatic, cyclic and aromatic hydrocarbons such as benzene, toluene, xylene, paraffin, tetrahydronaphthalene, alkylated naphthalenes and their derivatives such as methanol, ethanol, propanol, butanol, chloroform, carbon tetrachloride, cyclohexanol, cyclohexanone, chlorobenzene, isophorone, etc., and strongly polar solvents such as dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, water, etc. are suitable.
Aqueous formulations may be prepared from emulsion concentrates, pastes, dispersions, wettable powders or water-dispersible granules by adding water. To prepare emulsions, pastes and oil dispersions the ingredients as such or dissolved in an oil or solvent may be homogenized in water by means of wetting or dispersing agents, adherents or emulsifiers. Concentrates which are suitable for dilution with water may be prepared from active ingredient, wetting agent, adherent, emulsifying or dispersing agent and possibly solvent or oil.
Examples of surfactants are: alkali metal, alkaline earth metal and ammonium salts of ligninsulfonic acid, naphthalenesulfonic acids, phenolsulfonic acid, alkylaryl sulfonates, alkyl sulfates, and alkyl sulfonates, alkali metal and alkaline earth metal salts of dibutylnatphthalenesulfonic acid, lauryl ether sulfate, fatty alcohol sulfates, alkali metal and alkaline earth metal salts or fatty acids, salts of sulfated hexadecanols, heptadecanols, and octadecanols, salts or sulfated fatty alcohol glycol ethers, condensation products of sulfonated naphthalene and naphthalene derivatives with formaldehyde, condensation products of naphthalene or naphthalene or naphthalenesulfonic acids with phenol and formaldehyde, polyoxyethylene octylphenol ethers, ethoxylated isooctylphenol, ethoxylated octylphenol and ethoxylated nonylphenol, alkylphenol polyglycol ethers tributylphenyl polyglycol ethers, alkylaryl polyether alcohols, isotridecyl alcohol, fatty alcohol ethylene oxide condensates, ethoxylated castor oil, polyoxyethylene alkyl ethers, ethoxylated polyoxypropylene, lauryl alcohol polyglycol ether acetal, sorbitol esters, lignin, sulfite waste liquors and methyl cellulose.
Powders, dust and broadcasting agents may be prepared by mixing or grinding the active ingredients with a solid carrier.
Granules, e.g., coated, impregnated or homogeneous granules, may be prepared by bonding the active ingredients to solid carriers. Examples of solid carriers are mineral earths such as silicic acid, silica gels, silicates, talc, kaolin, attapulgus clay, limestone, lime, chalk, bole, loess, clay, dolomite, diatomaceous earth, calcium sulfate, magnesium sulfate, magnesium oxide, ground plastics, fertilizers such as ammonium sulfate, ammonium phosphate, ammonium nitrate, and ureas, and vegetable products such as grain flours, bark meal, wood meal, and nutshell meal, cellulosic powders, etc.
Examples of such formulations are as follows:
I. 90 parts by weight of compound no. 1006 is mixed with 10 parts by weight of N-methyl-alpha-pyrrolidone. A mixture is obtained which is suitable for application in the form of very fine drops.
II. 20 parts by weight of compound no. 1006 is dissolved in a mixture consisting of 80 parts by weight of xylene, 10 parts by weight of the adduct of 8 to 10 moles of ethylene oxide and 1 mole of oleic acid-N-monoethanolamide, 5 parts by weight of the calcium salt of dodecylbenzenesulfonic acid, and 5 parts by weight of the adduct of 40 moles of ethylene oxide and 1 mole of castor oil. By pouring the solution into water and uniformly distributing it therein, an aqueous dispersion is obtained.
III. 20 parts by weight of compound no. 1002 is dissolved in a mixture consisting of 40 parts by weight of cyclohexanone, 30 parts by weight of isobutanol, 20 parts by weight of the adduct of 7 moles of ethylene oxide and 1 mole of isooctylphenol, and 10 parts by weight of the adduct of 40 moles of ethylene oxide and 1 mole of castor oil. By pouring the solution into 1000,000 parts by weight of water and finely distributing it therein, an aqueous dispersion is obtained containing 0.02% by weight of the active ingredient.
IV. 20 parts by weight of compound no. 1049 is dissolved in a mixture consisting of 25 parts by weight of cyclohexanol, 65 parts by weight of a mineral oil fraction having a boiling point between 210.degree. and 280.degree. C., and 10 parts by weight of the adduct of 40 moles of ethylene oxide and 1 mole of castor oil. By pouring the solution into 100,000 parts by weight of water and uniformly distributing it therein, an aqueous dispersion is obtained containing 0.02% by weight of the active ingredient.
V. 20 parts by weight of compound no. 3038 is well mixed with 3 parts by weight of the sodium salt of diisobutylnaphthalene-alpha-sulfonic acid, 17 parts by weight of the sodium salt of a lignin-sulfonic acid obtained from a sulfite waste liquor, and 60 parts by weight of powdered silica gel, and triturated in a hammer mill. By uniformly distributing the mixture in 20,000 parts by weight of water, a spray liquor is obtained containing 0.1% by weight of the active ingredient.
VI. 3 parts by weight of compound no. 1075 is intimately mixed with 97 parts by weight of particulate kaolin. A dust is obtained containing 3% by weight of the active ingredient.
VII. 30 parts by weight of compound no. 1220 is intimately mixed with a mixture consisting of 92 parts by weight of powdered silica gel and 8 parts by weight of paraffin oil which has been sprayed onto the surface of this silica gel. A formulation of the active ingredient is obtained having good adherence.
VIII. 20 parts of compound no. 1026 is intimately mixed with 2 parts of the calcium salt of dodecylbenzenesulfonic acid, 8 parts of a fatty alcohol polyglycol ether, 2 parts of the sodium salt of a phenolsulfonic acid-urea-formaldehyde condensate and 68 parts of a paraffinic mineral oil. A stable oily dispersion is obtained.
The formulations contain from 0.1 to 95, and preferably 0.5 to 90, % by weight of active ingredient.
The active ingredient may be applied pre- or (preferably) postemergence. If certain crop plants tolerate the active ingredients less well, application techniques may be used in which the herbicidal agents are sprayed from suitable equipment in such a manner that the leaves of sensitive crop plants are if possible not touched, and the agents reach the soil or the unwanted plants growing beneath the crop plants (post-directed, lay-by treatment).
The application rates depend on the objective to be achieved, the time of the year, the plants to be combated and their growth stage, and are from 0.001 to 5.0, preferably 0.0 to 1.0, kg of active ingredient per hectare.
In view of the spectrum of unwanted plants which can be combated, the tolerance of the novel compounds by crop plants, and in view of the number of application methods possible, the compounds of the formula Ia, or agents containing them, may be used in a further large number of crops for removing unwanted plants. The following crops are given by way of example:
______________________________________Botanical name Common name______________________________________Allium cepa onionsAnanas comosus pineapplesArachis hypogaea peanuts (groundnuts)Asparagus officinalis asparagusAvena sativa oatsBeta vulgaris spp. altissima sugarbeetsBeta vulgaris spp. rapa fodder beetsBeta vulgaris spp. esculenta table beets, red beetsBrassica napus var. napus rapeseedBrassica napus var. napobrassica swedesBrassica napus var. rapa turnipsBrassica rapa var. silvestrisCamellia sinensis tea plantsCarthamus tinctorius safflowerCarya illinoinensis pecan treesCitrus limon lemonsCitrus maxima grapefruitsCitrus reticulata mandarinsCitrus sinensis orange treesCoffea arabica (Coffea canephora, coffee plantsCoffea liberica)Cucumis melo melonsCucumis sativus cucumbersCynodon dactylon BermudagrassElais guineensis oil palmsFragaria vesca strawberriesGlycine max soybeansGossypium hirsutum (Gossypium cottonarboreum, Gossypium herbaceum,Gossypium vitifolium)Helianthus annuus sunflowersHelianthus tuberosus Jerusalem artichokeHevea brasiliensis rubber plantsHordeum vulgare barleyHumulus lupulus hopsIpomoea batatas sweet potatoesJuglans regia walnut treesLactuca sativa lettuceLens culinaris lentilsLinum usitatissimum flaxLycopersicon lycopersicum tomatoesMalus spp. apple treesManihot esculenta cassavaMedicago sativa alfalfa (lucerne)Mentha piperita peppermintMusa spp. banana plantsNicotiana tabacum (N. rustica) tobaccoOlea europaea olive treesOryza sativa ricePanicum miliaceum milletPhaseolus lunatus limabeansPhaseolus mungo mungbeansPhaseolus vulgaris snapbeans, green beans, dry beansPennisetum glaucum pearl milletPetroselinum crispum spp. tuberosum parsleyPicea abies Norway spruceAbies alba fir treesPinus spp. pine treesPisum sativum English peasPrunus avium cherry treesPrunus domestica plum treesPrunus dulcis almond treesPrunus persica peach treesPyrus communis pear treesRibes sylvestre redcurrantsRibes uva-crispa gooseberriesRicinus communis castor-oil plantsSaccharum officinarum sugar caneSecale cereale ryeSesamum indicum sesameSolanum tuberosum Irish potatoesSorghum bicolor (s. vulgare) sorghumSorghum dochna sorgoSpinacia oleracea spinachTheobroma cacao cacao plantsTrifolium pratense red cloverTriticum aestivum wheatTriticum durum durum wheatVaccinium corymbosum blueberriesVaccinium vitis-idaea cranberriesVicia faba tick beansVigna sinensis (V. unguiculata) cow peasVitis vinifera grapesZea mays Indian corn, sweet corn, maize______________________________________
To increase the spectrum of action and to achieve synergistic effects, the isoxazole-(isothiazole)-5-carboxamides of the formula Ia may be mixed and applied together with numerous representatives of other herbicidal or growth-regulating active ingredient groups. Examples of suitable components are diazines, 4H-3,1-benzoxazine derivatives, benzothiadiazinones, 2,6-dinitroanilines, N-phenylcarbamates, thiolcarbamates, halocarboxylic acids, trazines, amides, ureas, diphenyl ethers, triazinones, uracils, benzofuran derivatives, cyclohexane-1,3-dione derivatives, quinolinecarboxylic acids, sulfonylureas, imidazolinones, (hetero)aryloxyphenylpropionic acids and salts, esters and amides thereof, etc.
It may also be useful to apply the compounds of the formula Ia, either alone or in combination with other herbicides, in admixture with other crop protection agents, e.g., agents for combating pests or phytopathogenic fungi or bacteria. The compounds may also be mixed with solutions of mineral salts used to remedy nutritional or trace element deficiencies. Non-phytotoxic oils and oil concentrates may also be added.
USE EXAMPLES
The action of the isoxazole-(isothiazole)-5-carboxamides of the formula Ia on plant growth is demonstrated in greenhouse experiments.
The vessels employed were plastic flowerpots having a volume of 300 cm.sup.3 and filled with a sandy loam containing about 3.0% humus. The seeds of the test plants were sown separately, according to species.
For the preemergence treatment, the formulated active ingredients were applied to the surface of the soil immediately after the seeds had been sown. The compounds were emulsified or suspended in water as vehicle, and sprayed through finely distributing nozzles. The application rate was 0.5 kg of active ingredient per hectare. After the agents had been applied, the vessels were lightly sprinkler-irrigated to induce germination and growth. Transparent plastic covers were then placed on the vessels until the plants had taken root. The cover ensure uniform germination of the plants, insofar as this was not impaired by the active ingredients.
For postemergence treatment, either plants which had been sown in the pots and grown there were selected, or they were cultivated separately as seedlings and transplanted to the pots a few days before being treated.
The plants were grown, depending on growth form, to a height of 3 to 15 cm before being treated with the active ingredients, which were suspended or emulsified in water as vehicle, and sprayed through finely distributing nozzles. The application rates for postemergence treatment were 1.0 and 3.0 kg/ha.
The pots were set up in the greenhouse, species from warmer climates in warmer areas (20.degree. to 35.degree. C.) and species from moderate climates at 10.degree. to 25.degree. C. The experiments were run for from 2 to 4 weeks. During this time the plants were tended and their reactions to the various treatments assessed. The assessment scale was 0 to 100, 100 denoting nonemergence or complete destruction of at least the visible plant parts, and 0 denoting no damage or normal growth.
The pants used in the greenhouse experiments were Abutilon theophrasti, Centaurea cyanus, Chenopdium album, Chrysanthemum coronarium Echinochloa crus-galli, Gallium aparine, Ipomoea spp., Lolium multiflorum, Mentha piperita, Mercurialis annua, Solanum nigrum, Triticum aestivum, Viola spp. and Zea mays.
Active ingredients no. 1006 selected by way of example combated unwanted plants excellently on preemergence application of 3.0 kg/ha.
For example compounds nos. 1004, 1014, 3018, 1026, 1006, 1049 and 1022 had, on postemergence application of 1 to 3 kg/ha, a herbicidal action on a broad spectrum of unwanted plants. Compounds nos. 1075 and 3038 also had a very good herbicidal action on broadleaved plants and were tolerated by Indian corn. Compound no. 1211 had an excellent herbicidal action and was tolerated by wheat.

Isoxazole(isothiazole)-5-carboxamides

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Adams, J. Chem. Soc. 1959 3061.
Nesi, J. Chem. Soc. Perkin I 1980 1667.