CA1231711A - Fluoroazolyl methyl oxiranes - Google Patents
Fluoroazolyl methyl oxiranesInfo
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- CA1231711A CA1231711A CA000524386A CA524386A CA1231711A CA 1231711 A CA1231711 A CA 1231711A CA 000524386 A CA000524386 A CA 000524386A CA 524386 A CA524386 A CA 524386A CA 1231711 A CA1231711 A CA 1231711A
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Abstract
ABSTRACT OF THE DISCLOSURE
Fluoroazolyl methyl oxiranes of the formula II
II
wherein Az is 1,2,4-triazolyl, R1 is hydrogen, C1-C6-alkyl which is unsubstituted or substituted by halogen or cyano, or C1-C3-phenylalkyl which is unsubstituted or substituted by halogen, C1-C3-alkyl, C1-C3-alkoxy, C1-C3-halogenoalkyl, nitro, cyano, carboxyl or C1-C6-alkoxycarbonyl R2 is C1-C10-alkyl which is unsubstituted or substituted by C1-C3-alkoxy, phenyl or C1-C3-phenylalkyl, it being possible for the phenyl nuclei in turn to be unsubstituted or substituted by halogen, C1-C3-alkyl, C1-C3-alkoxy, C1-C3-halogenoalkyl, nitro, cyano, carboxyl or C1-C6-alkoxycarbonyl. Methods of preparing these products are also disclosed. The fluoroazolyl methyl oxiranes of the formula II are useful as intermediates in the preparation of the corresponding fluoroazolylpropane derivatives. The corresponding fluoroazolylpropane derivatives are useful as active ingredients in the preparation of compositions having plant growth regulating activity and for the control of harmful microorganisms.
Fluoroazolyl methyl oxiranes of the formula II
II
wherein Az is 1,2,4-triazolyl, R1 is hydrogen, C1-C6-alkyl which is unsubstituted or substituted by halogen or cyano, or C1-C3-phenylalkyl which is unsubstituted or substituted by halogen, C1-C3-alkyl, C1-C3-alkoxy, C1-C3-halogenoalkyl, nitro, cyano, carboxyl or C1-C6-alkoxycarbonyl R2 is C1-C10-alkyl which is unsubstituted or substituted by C1-C3-alkoxy, phenyl or C1-C3-phenylalkyl, it being possible for the phenyl nuclei in turn to be unsubstituted or substituted by halogen, C1-C3-alkyl, C1-C3-alkoxy, C1-C3-halogenoalkyl, nitro, cyano, carboxyl or C1-C6-alkoxycarbonyl. Methods of preparing these products are also disclosed. The fluoroazolyl methyl oxiranes of the formula II are useful as intermediates in the preparation of the corresponding fluoroazolylpropane derivatives. The corresponding fluoroazolylpropane derivatives are useful as active ingredients in the preparation of compositions having plant growth regulating activity and for the control of harmful microorganisms.
Description
~3~7~ 21489-6443E
~ he present application has been divided out of Canadian Patent Application Serial No. 444,679 filed January 4, 1986.
The present invention relates to novel fluoroazolyl methyl oxiranes. The invention also relates to the preparation of these substances and to their use in the preparation of novel, substituted fluoroazolylpropane derivatives as disclosed in our Application, Serial No. 444~679. The substituted fluoroazolyl-propane derivatives of Application 444,679 are disclosed therein to be useful in the regulation of plant growth and in controlling harmful microorganisms.
The fluoroazolyl methyl oxiranes according to the invention have the formula II
Az - CF ~ -CH2 II
Il \/
R O
wherein Az is 1,2.4,-triazolyl, Rl is hydrogen, Cl-C6-alkyl which is unsu~stituted or substituted by halogen or cyano, or Cl-C3-phenylalkyl which is unsubstituted or substituted by halogen, Cl-C3-~alkyl, Cl-C3-alkoxy, Cl-C3-halogenalkYl, nitro, cyano, carboxyl or Cl-C6-alkoxycarbonyl, R is C1-C10-alkyl which is unsubstituted or substituted by Cl-C3-alkoxy, phenyl or Cl-C3-phenylalkyl, it being possible for the phenyl nuclei in turn to be unsubstituted or substituted by halogen, ~Z3~7~.~
Cl-C3-alkyl, Cl-C3-alkoxy, Cl-C3-halogenoalkyl, nitro, cyano, carboxyl or Cl-C6-alkoxycarbonyl.
The oxiranes of the formula II are intermediates which are used in the preparation of the ~aluable active substances of the formula I.
F O
Az - C - C - CH2 - X - R
Rl R2 in which Rl, R and Az are as defined above,and R3 is hydrogen Cl-C6-alkyl, Cl-C6-alkylcarbonyl or Cl-C3-phenylalkyl which is unsubstituted or substituted by halogen, Cl-C3-alkoxy, Cl-C3-alkyl, Cl-C3-alkyl, C1-C3-halogenoalkyl, cyano, carboxyl or Cl-C6-alkoxycarbonyl,R5 is an unsubstituted or substituted radical selected from the series comprising Cl-C8-alkyl, C3-C8-cycloalkyl, C3-C6-alkenyl, C3-C6-alkynyl, phenyl, naphthyl, biphenyl, benzylphenyl, ~enzyloxyphenyl, phenoxyphenyl and aralkyl, the substituents being selected from the series comprising halogen, cyano, Cl-C3-alkyl, Cl-C5-alkoxy, Cl-C5-halogenoalkyl, Cl-C3-alkylthio, Cl-C3-halogenoalkyl, Cl-C3~
halogenoalkylthio, nitro and thiocyano, and X is oxygen or sulfur.
The oxiranes of the formula II can be prepared by reacting the parent ketones of the formula V
7~
F R
Az - C - C = O (V) in which Rl, R and Az are as defined above in the presence of strong bases, such as alkali and alkaline earth metal alcoholates, alkali metal hydroxides or alkali or alkaline earth metal hydrides, in dimethyl sulfoxide or one of the other solvents described below in the preparation of the compounds of formula I with dimethylsulfonium methylide, dimethyloxosulfonium methylide or the corresponding salts, such as trimethylsulfonium iodide or trimethyloxosulfonlum iodide. Under suitable circumstances, it is also possible to effect the production of the sulfonium ylide or the reaction of the sulfonium salt with the base by the phase transfer process.
The following could be used as suitable phase transfer catalysts:
quaternary ammonium salts, such as trialkyl~phenylalkylammonium salts or tetraalkylammonium salts, quaternary phosphonium salts, such as tetraalkylphosphonium salts, or crown ethers, such as 15-crown-5 or 18-crown-6. In this reaction, the sulfonium ylide is formed in situ and reacts directly with the ketone of the ~ormula V to give the oxirane of the formula II.
The reaction is carried out at temperatures from O to 120C.
Analogous reactions are known from the literature;
cf. JACS, 87, 1353 (1965). In principle, the reaction can be carried out analogously to the reactions described therein.
~Z3~7~
Ketones of the formula V are also novel, are the subject of our further copending divisional application serial No.
444,679 and can be prepared from the ~ - halogenoketones, which are known per se, of the formula VI
F R
Hal - C - C = O (VI) R
in which Rl and R are as defined above and Hal is chlorine or bromine, by reac-ting these compounds, in the presence of a base, with azoles of the formula VII
H - Az (VII) in which Az is a defined above.
The ketones of the formula V can also be obtained by reacting an azolylmethyl ketone of the formula VIII
Az - CHF - C - R (VIII) in the presence o~ a base with a compound of the formula IX
Rl (IX) in which Rl,R2and Az are asdefined above and Z is a halogen atom or an organic or inorganic acid radical.
The preparation of the ketones of the formula V is effected in the conventional inert solvents and, if desired, at an elevated temperature.
~;~3~7~L
The compounds o the formulae VI, VII, vrII and I~
are known and are in some cases commercially available or can be prepared by known methods.
The compounds of the formula I are prepared by pro-ceSses known per se.
Thus the compounds of the formula I are obtained by reacting an azolylmethyloxirane of the formula II
F R
Az ~ CH2 (II) Rl V
in which Rl, R2 and Az are as defined above in the presence of a base and in an inert solvent, with an alcohol or thioalcohol of the formula III
H - X - R (III) in which X and R5 are as defined above and, if desired, by etherifying or esterifying the resultlng product of the formula Ia F R
Az - ~ - f - CH2 - X - R (Ia) Rl OH
by reacting it with an etherifying or esterifying agent of the formula IV
Y - R (IV) in which R3 is as defined above and Y is a halogen atom or an organic or inorganic acid radical.
~.~3~7~
The reactions (II with III) is advantageously carried out in the presence of catalytic amounts of bases as condensation agents. Suitable condensation ayents are organic and inorganic bases, for example tertiary amines, such as trialkylamines (trimethylamine, triethylamine, tripropylamine etc.), pyridine and pyridine bases (4-dimethylaminopyridine, 4-pyrrolidylamino-pyridine etc.), oxides, hydrides and hydroxides, carbo~ates and bicarbonates of alkali and alkaline earth metals (CaO, BaO, NaOH, LiOH, CaH2, KOH, NaH, Ca(OH)2, KHCO3, NaHCO3, Ca(HCO3~2 K2CO3 and Na2CO3), and alkali metal acetates, such as CH3COONa ox CH3COOX. In addition, alkali metal alcoholates, such as C2HsONa, n-C3H7ONa, (CH3)3CO-K etc., are also suitable.
The reaction (II with III) is preferably carried out in an organic solvent which is relatively polar, but inert towards the reaction, for example N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, acetonitrile, benzonitrile, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, dioxane, tetrahydrofuran and others. Reactions of this type can, however, also be carried out in combination with other solvents which are inert towards the reaction, for example benzene, toluene, xylene, hexane, petroleum ether, chloro-benzene, nitrobenzene and others. The reaction temperatures are within a temperature range from 20C to 250C, preferably 80C to 180C.
~ e The optional conversion of the compounds of the subformula Ia into the compounds of the formula I in which R3 has a definition other than hydrogen is advantageously carried out in an inert organic solvent. Suitable solvents are aprotic solvents, such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, acetonitrile, benzonitrile, N~methylpyrrolidone, N-methylpiperidone, benzene, toluene, xylene, hexane, cyclohexane, chlorobenzene, nitrobenzene and others.
In the e~ent that the -o-R3 group is an ether group, Y is usually halogen, such as chlorine, bromine and iodine, or acid radicals derived from strong acids, such as sulfuric acid, phosphoric acid, sulfonic acids, preferably halogeno-alkylsulfonic acids, or halogenoalkanecarboxylic acids, such as trifluoroacetic acid. Typical representatives of such acid derivatives are dimethyl sulfate, diethyl sulfate and methyl trifluoromethanesulfonate. In the event that the -o-R3 group is an ester group, Y is generally halogen, such as chlorine or bromine, or acid radicals of acids which can form an anhydride with the acyl radical which is transferred. This is preferably an anhydride containing the same acid. Consequently, the reagent Y-R is then, for example, acetic anhydride, propionic anhydride, benzoic anhydride, benzenesulfonic anhydride or trifluoromethanesulfonic anhydride.
The etherification or esterification of the co~pounds of the subformula Ia is advantageously effected in the presence ~ ~3~
~.~ ,..~
of bases, such as alcoholates, hydroxides, hydrides, carbonates or bicarbonates of alkali or alkaline earth metals. The reaction temperatures are 20-150C, preferably 60-120C.
The compounds of the formula I are obtained in the form of mixtures of diastereomers. The invention relates to all the diastereomeric forms of the active substances of the formula I and to mixtures thereof. It therefore embraces both the pure diastereomers and the lndividual optical isomers of the enantiomer pairs which are embraced.
The alcohols or thioalcohols of the formula ~II and also the etherifying and esterifying agents of the formula IV
are known or are prepared by methods known per se.
The term alkyl itself or as a constituent of another substituent, such as alkoxy, alkylthio, halogenoalkyl, aralkyl or alkylcarbonyl, is to be understood, depending on the number of carbon atoms indicated, as meaning, for example, the following groups: methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl r octyl, nonyl or decyl and isomers thereof, for example isopropyl, isobutyl, sec.-butyl, tertO-butyl, isopentyl etcO Halogenoalkyl is a monohalogenated to perhalogenated alkyl substituent, for example CHC12, CHF2, CH2Cl, CC13, CH2F, -CH2CH2Cl, CHBr2 etc.
Here and in the following text, halogen is to be understood as meaning fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine and especially fluorine and chlorine.
Napthyl is ~-napthyl or ~-naphthyl, preferably ~-naphthyl~
~.Z~ 7~3L
Alkenyl is, for example, l-propenyl, allyl, l-butenyl, 2-butenyl or 3-butenyl, and alkynyl is, for example, l-propynyl or propargyl.
Aryl is, for example, naphthyl, particularly phenyl, and aralkyl is a lower alkyl radical which is substituted by an aromatic group, for example benzyl or phenylethyl, Depending on the number of carbon atoms, cycloalkyl is, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl etc.
The compounds of -the formula I can be obtained in the form of the free organic molecules or acid addition salts, quaternary azolium salts and metal complexes thereof. The free molecules are preferred. Examples of salt-forming acids are inorganic acids: a hydrogen halide acid, such as hydrofluoric acid, hydrochloric aeid, hydrobromic acid or hydrlodic acid, and sulfuric acid, phosphoric acid, phosphorous acid and nitric acid, and organic acids, such as acetic acid, trifluoroacetic acid, trichloroacetic acid, propionic acid, glycollic acid, thiocyanic acid, lactic acid, succinic acid, citric acid, benzoic acid, cinnamic acid~ oxalic acid, formic acid, benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, tr;~fluoromethanesulfonic acid, salicylic acid, p-aminosalicyllc acid, 2-phenoxybenzoic acid or 2-acetoxybenzoic acid.
Metal complexes of the formula I consist of the parent organic molecule and an inorganic or organic metal salt, for example the halides, nitrates, sulfates, phosphates, acetates, 317~:~
trifluoroacetates, trichloroacetates, propionates, tartrates, sulfonates, salicylates, benzoates etc., of the elements of the third and fourth main groups, such as aluminium, tim or lead, and of the first to eight subgroups, such as chromium, manganese, iron, cobalt, nickel, copper, zinc, silver, mercury, etc. The subgroup elements of the 4th period are preferred. The metals can be present in these complexes in the various valencies appropriate to them. The metal complexes of the formula I can exist in a mononuclear or polynuclear form, i.e. they can contain one or more organic molecular moieties as ligands. Complexes containing the metals copper, zinc, manganese and tin are preferred.
l-Hydroxyethylazole deri~atives are known as plant growth-regulators and fungicides from the literature, for example from European Patent Application 40,345.
The compounds of the formula I are oils, resins or, mainly, solids which are stable at room temperature and which are distinguished by very valuable microbicidal and growth-regulating properties. They can be employed in a preventive or curative manner in the agricultural sector or related Eields, for controlling microorganisms which damage plants and for regulating plant growth, the triazolylmethyl derivati~es within the scope of the formula I being preferred. The active substances, ac-cording to the invention, of the formula I are distinguished by being very well tolerated by crop plants.
~Z317~1 Compounds of ~ormula I which are pre~erred by virtue o~ their pronounced growth-regulatlng and/or microbicidal action are those in which Az is 1,2,4-triazolyl, Rl is hydrogen, Cl-C6-alkyl which i5 unsubstituted or substituted by halogen or cyano, or Cl-C3-phenylalkyl ~hich is unsubstituted or substituted by halogen, Cl-C3-alkyl, Cl-C3 alkoxy, Cl-C3-halogenoalkyl, nitro, cyano, carboxyl or Cl-C6-alkoxycarbonyl, R is Cl-C10-alkyl which is unsubstituted or su~stituted by Cl-C3-alkoxy, phenyl or Cl-C3-phenylalkyl, it being possible for the phenyl nuclei in turn to be unsubstituted or substituted by halogen, Cl-C3-alkyl, Cl-C3-alkoxy, Cl-C3-halogenoalkyl, nitro, cyano, carboxyl or Cl-C6-alkoxycarbonyl, R3 is hydrogen, Cl-C6-alkyl, Cl-C6-alkylcarbonyl or Cl-C3-phenylalky~ which is unsubstituted or substituted by halogen, Cl-C3-alkoxy, Cl-C3-alkyl, Cl-C3-halogenoalkyl, cyano, carboxyl or Cl-C6-alkoxycarbonyl, R5 is an unsubstituted or monosubstituted or polysubstituted radical selected from the series comprising Cl-C8-alkyl, C3-C8-cycloalkyl, C3-C6-alkenyl, C3-C6-alkynyl, phenyl, naphthyl, biphenyl, benzylphenyl, benzyloxyphenyl, phenoxyphenyl and aralkyl, the substituents being selected from the series comprising halogen, cyano, Cl-C3-alkyl, Cl-C5-alkoxy, Cl-C5-halogenoalkyl, Cl-C3-alkylthio, Cl-C3-halogenoalkyl, Cl-C3-halogenoalkylthio, nitro and/or thiocyano, and X is oxygen or sulfur.
~Z3~7~l~
Subgroups which may be mentioned as enjoying a further preference are those comprising compounds of the formula I in which a) is 1,2,4-triazolyl or b) R2 is Cl-C6-alkyl or benzyl which is unsubstituted or substituted by halogen or c) Rl and R3 are hydrogen or Cl-C~-alkyl or d) R5 is phenyl which is substituted by halogen or e) X is oxy~en.
Within the subgroup b), preferred compounds are those in which R is tert.-butyl or i-propyl.
Within subgroup d), preferred compounds are those in which R5 is phenyl which is substituted in the 4~position by halogen.
Compounds whlch should be mentioned as a particularly preferred subgroup of compounds of the formula ~ are those in which Az is 1,2,4,-triazolyl, Rl and R3 are hydrogen or Cl-C4-alkyl, R2 is ter-t.-butyl or i-propyl, R5 lS phenyl which ~s substituted in the 4-position by halogen and X is oxygen.
The follo~ing are examples of preferred individual compounds of the formula I 1-(4-fluorophenoxy)-2-tert.-butyl-
~ he present application has been divided out of Canadian Patent Application Serial No. 444,679 filed January 4, 1986.
The present invention relates to novel fluoroazolyl methyl oxiranes. The invention also relates to the preparation of these substances and to their use in the preparation of novel, substituted fluoroazolylpropane derivatives as disclosed in our Application, Serial No. 444~679. The substituted fluoroazolyl-propane derivatives of Application 444,679 are disclosed therein to be useful in the regulation of plant growth and in controlling harmful microorganisms.
The fluoroazolyl methyl oxiranes according to the invention have the formula II
Az - CF ~ -CH2 II
Il \/
R O
wherein Az is 1,2.4,-triazolyl, Rl is hydrogen, Cl-C6-alkyl which is unsu~stituted or substituted by halogen or cyano, or Cl-C3-phenylalkyl which is unsubstituted or substituted by halogen, Cl-C3-~alkyl, Cl-C3-alkoxy, Cl-C3-halogenalkYl, nitro, cyano, carboxyl or Cl-C6-alkoxycarbonyl, R is C1-C10-alkyl which is unsubstituted or substituted by Cl-C3-alkoxy, phenyl or Cl-C3-phenylalkyl, it being possible for the phenyl nuclei in turn to be unsubstituted or substituted by halogen, ~Z3~7~.~
Cl-C3-alkyl, Cl-C3-alkoxy, Cl-C3-halogenoalkyl, nitro, cyano, carboxyl or Cl-C6-alkoxycarbonyl.
The oxiranes of the formula II are intermediates which are used in the preparation of the ~aluable active substances of the formula I.
F O
Az - C - C - CH2 - X - R
Rl R2 in which Rl, R and Az are as defined above,and R3 is hydrogen Cl-C6-alkyl, Cl-C6-alkylcarbonyl or Cl-C3-phenylalkyl which is unsubstituted or substituted by halogen, Cl-C3-alkoxy, Cl-C3-alkyl, Cl-C3-alkyl, C1-C3-halogenoalkyl, cyano, carboxyl or Cl-C6-alkoxycarbonyl,R5 is an unsubstituted or substituted radical selected from the series comprising Cl-C8-alkyl, C3-C8-cycloalkyl, C3-C6-alkenyl, C3-C6-alkynyl, phenyl, naphthyl, biphenyl, benzylphenyl, ~enzyloxyphenyl, phenoxyphenyl and aralkyl, the substituents being selected from the series comprising halogen, cyano, Cl-C3-alkyl, Cl-C5-alkoxy, Cl-C5-halogenoalkyl, Cl-C3-alkylthio, Cl-C3-halogenoalkyl, Cl-C3~
halogenoalkylthio, nitro and thiocyano, and X is oxygen or sulfur.
The oxiranes of the formula II can be prepared by reacting the parent ketones of the formula V
7~
F R
Az - C - C = O (V) in which Rl, R and Az are as defined above in the presence of strong bases, such as alkali and alkaline earth metal alcoholates, alkali metal hydroxides or alkali or alkaline earth metal hydrides, in dimethyl sulfoxide or one of the other solvents described below in the preparation of the compounds of formula I with dimethylsulfonium methylide, dimethyloxosulfonium methylide or the corresponding salts, such as trimethylsulfonium iodide or trimethyloxosulfonlum iodide. Under suitable circumstances, it is also possible to effect the production of the sulfonium ylide or the reaction of the sulfonium salt with the base by the phase transfer process.
The following could be used as suitable phase transfer catalysts:
quaternary ammonium salts, such as trialkyl~phenylalkylammonium salts or tetraalkylammonium salts, quaternary phosphonium salts, such as tetraalkylphosphonium salts, or crown ethers, such as 15-crown-5 or 18-crown-6. In this reaction, the sulfonium ylide is formed in situ and reacts directly with the ketone of the ~ormula V to give the oxirane of the formula II.
The reaction is carried out at temperatures from O to 120C.
Analogous reactions are known from the literature;
cf. JACS, 87, 1353 (1965). In principle, the reaction can be carried out analogously to the reactions described therein.
~Z3~7~
Ketones of the formula V are also novel, are the subject of our further copending divisional application serial No.
444,679 and can be prepared from the ~ - halogenoketones, which are known per se, of the formula VI
F R
Hal - C - C = O (VI) R
in which Rl and R are as defined above and Hal is chlorine or bromine, by reac-ting these compounds, in the presence of a base, with azoles of the formula VII
H - Az (VII) in which Az is a defined above.
The ketones of the formula V can also be obtained by reacting an azolylmethyl ketone of the formula VIII
Az - CHF - C - R (VIII) in the presence o~ a base with a compound of the formula IX
Rl (IX) in which Rl,R2and Az are asdefined above and Z is a halogen atom or an organic or inorganic acid radical.
The preparation of the ketones of the formula V is effected in the conventional inert solvents and, if desired, at an elevated temperature.
~;~3~7~L
The compounds o the formulae VI, VII, vrII and I~
are known and are in some cases commercially available or can be prepared by known methods.
The compounds of the formula I are prepared by pro-ceSses known per se.
Thus the compounds of the formula I are obtained by reacting an azolylmethyloxirane of the formula II
F R
Az ~ CH2 (II) Rl V
in which Rl, R2 and Az are as defined above in the presence of a base and in an inert solvent, with an alcohol or thioalcohol of the formula III
H - X - R (III) in which X and R5 are as defined above and, if desired, by etherifying or esterifying the resultlng product of the formula Ia F R
Az - ~ - f - CH2 - X - R (Ia) Rl OH
by reacting it with an etherifying or esterifying agent of the formula IV
Y - R (IV) in which R3 is as defined above and Y is a halogen atom or an organic or inorganic acid radical.
~.~3~7~
The reactions (II with III) is advantageously carried out in the presence of catalytic amounts of bases as condensation agents. Suitable condensation ayents are organic and inorganic bases, for example tertiary amines, such as trialkylamines (trimethylamine, triethylamine, tripropylamine etc.), pyridine and pyridine bases (4-dimethylaminopyridine, 4-pyrrolidylamino-pyridine etc.), oxides, hydrides and hydroxides, carbo~ates and bicarbonates of alkali and alkaline earth metals (CaO, BaO, NaOH, LiOH, CaH2, KOH, NaH, Ca(OH)2, KHCO3, NaHCO3, Ca(HCO3~2 K2CO3 and Na2CO3), and alkali metal acetates, such as CH3COONa ox CH3COOX. In addition, alkali metal alcoholates, such as C2HsONa, n-C3H7ONa, (CH3)3CO-K etc., are also suitable.
The reaction (II with III) is preferably carried out in an organic solvent which is relatively polar, but inert towards the reaction, for example N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, acetonitrile, benzonitrile, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, dioxane, tetrahydrofuran and others. Reactions of this type can, however, also be carried out in combination with other solvents which are inert towards the reaction, for example benzene, toluene, xylene, hexane, petroleum ether, chloro-benzene, nitrobenzene and others. The reaction temperatures are within a temperature range from 20C to 250C, preferably 80C to 180C.
~ e The optional conversion of the compounds of the subformula Ia into the compounds of the formula I in which R3 has a definition other than hydrogen is advantageously carried out in an inert organic solvent. Suitable solvents are aprotic solvents, such as N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, acetonitrile, benzonitrile, N~methylpyrrolidone, N-methylpiperidone, benzene, toluene, xylene, hexane, cyclohexane, chlorobenzene, nitrobenzene and others.
In the e~ent that the -o-R3 group is an ether group, Y is usually halogen, such as chlorine, bromine and iodine, or acid radicals derived from strong acids, such as sulfuric acid, phosphoric acid, sulfonic acids, preferably halogeno-alkylsulfonic acids, or halogenoalkanecarboxylic acids, such as trifluoroacetic acid. Typical representatives of such acid derivatives are dimethyl sulfate, diethyl sulfate and methyl trifluoromethanesulfonate. In the event that the -o-R3 group is an ester group, Y is generally halogen, such as chlorine or bromine, or acid radicals of acids which can form an anhydride with the acyl radical which is transferred. This is preferably an anhydride containing the same acid. Consequently, the reagent Y-R is then, for example, acetic anhydride, propionic anhydride, benzoic anhydride, benzenesulfonic anhydride or trifluoromethanesulfonic anhydride.
The etherification or esterification of the co~pounds of the subformula Ia is advantageously effected in the presence ~ ~3~
~.~ ,..~
of bases, such as alcoholates, hydroxides, hydrides, carbonates or bicarbonates of alkali or alkaline earth metals. The reaction temperatures are 20-150C, preferably 60-120C.
The compounds of the formula I are obtained in the form of mixtures of diastereomers. The invention relates to all the diastereomeric forms of the active substances of the formula I and to mixtures thereof. It therefore embraces both the pure diastereomers and the lndividual optical isomers of the enantiomer pairs which are embraced.
The alcohols or thioalcohols of the formula ~II and also the etherifying and esterifying agents of the formula IV
are known or are prepared by methods known per se.
The term alkyl itself or as a constituent of another substituent, such as alkoxy, alkylthio, halogenoalkyl, aralkyl or alkylcarbonyl, is to be understood, depending on the number of carbon atoms indicated, as meaning, for example, the following groups: methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl r octyl, nonyl or decyl and isomers thereof, for example isopropyl, isobutyl, sec.-butyl, tertO-butyl, isopentyl etcO Halogenoalkyl is a monohalogenated to perhalogenated alkyl substituent, for example CHC12, CHF2, CH2Cl, CC13, CH2F, -CH2CH2Cl, CHBr2 etc.
Here and in the following text, halogen is to be understood as meaning fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine and especially fluorine and chlorine.
Napthyl is ~-napthyl or ~-naphthyl, preferably ~-naphthyl~
~.Z~ 7~3L
Alkenyl is, for example, l-propenyl, allyl, l-butenyl, 2-butenyl or 3-butenyl, and alkynyl is, for example, l-propynyl or propargyl.
Aryl is, for example, naphthyl, particularly phenyl, and aralkyl is a lower alkyl radical which is substituted by an aromatic group, for example benzyl or phenylethyl, Depending on the number of carbon atoms, cycloalkyl is, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl etc.
The compounds of -the formula I can be obtained in the form of the free organic molecules or acid addition salts, quaternary azolium salts and metal complexes thereof. The free molecules are preferred. Examples of salt-forming acids are inorganic acids: a hydrogen halide acid, such as hydrofluoric acid, hydrochloric aeid, hydrobromic acid or hydrlodic acid, and sulfuric acid, phosphoric acid, phosphorous acid and nitric acid, and organic acids, such as acetic acid, trifluoroacetic acid, trichloroacetic acid, propionic acid, glycollic acid, thiocyanic acid, lactic acid, succinic acid, citric acid, benzoic acid, cinnamic acid~ oxalic acid, formic acid, benzenesulfonic acid, p-toluenesulfonic acid, methanesulfonic acid, tr;~fluoromethanesulfonic acid, salicylic acid, p-aminosalicyllc acid, 2-phenoxybenzoic acid or 2-acetoxybenzoic acid.
Metal complexes of the formula I consist of the parent organic molecule and an inorganic or organic metal salt, for example the halides, nitrates, sulfates, phosphates, acetates, 317~:~
trifluoroacetates, trichloroacetates, propionates, tartrates, sulfonates, salicylates, benzoates etc., of the elements of the third and fourth main groups, such as aluminium, tim or lead, and of the first to eight subgroups, such as chromium, manganese, iron, cobalt, nickel, copper, zinc, silver, mercury, etc. The subgroup elements of the 4th period are preferred. The metals can be present in these complexes in the various valencies appropriate to them. The metal complexes of the formula I can exist in a mononuclear or polynuclear form, i.e. they can contain one or more organic molecular moieties as ligands. Complexes containing the metals copper, zinc, manganese and tin are preferred.
l-Hydroxyethylazole deri~atives are known as plant growth-regulators and fungicides from the literature, for example from European Patent Application 40,345.
The compounds of the formula I are oils, resins or, mainly, solids which are stable at room temperature and which are distinguished by very valuable microbicidal and growth-regulating properties. They can be employed in a preventive or curative manner in the agricultural sector or related Eields, for controlling microorganisms which damage plants and for regulating plant growth, the triazolylmethyl derivati~es within the scope of the formula I being preferred. The active substances, ac-cording to the invention, of the formula I are distinguished by being very well tolerated by crop plants.
~Z317~1 Compounds of ~ormula I which are pre~erred by virtue o~ their pronounced growth-regulatlng and/or microbicidal action are those in which Az is 1,2,4-triazolyl, Rl is hydrogen, Cl-C6-alkyl which i5 unsubstituted or substituted by halogen or cyano, or Cl-C3-phenylalkyl ~hich is unsubstituted or substituted by halogen, Cl-C3-alkyl, Cl-C3 alkoxy, Cl-C3-halogenoalkyl, nitro, cyano, carboxyl or Cl-C6-alkoxycarbonyl, R is Cl-C10-alkyl which is unsubstituted or su~stituted by Cl-C3-alkoxy, phenyl or Cl-C3-phenylalkyl, it being possible for the phenyl nuclei in turn to be unsubstituted or substituted by halogen, Cl-C3-alkyl, Cl-C3-alkoxy, Cl-C3-halogenoalkyl, nitro, cyano, carboxyl or Cl-C6-alkoxycarbonyl, R3 is hydrogen, Cl-C6-alkyl, Cl-C6-alkylcarbonyl or Cl-C3-phenylalky~ which is unsubstituted or substituted by halogen, Cl-C3-alkoxy, Cl-C3-alkyl, Cl-C3-halogenoalkyl, cyano, carboxyl or Cl-C6-alkoxycarbonyl, R5 is an unsubstituted or monosubstituted or polysubstituted radical selected from the series comprising Cl-C8-alkyl, C3-C8-cycloalkyl, C3-C6-alkenyl, C3-C6-alkynyl, phenyl, naphthyl, biphenyl, benzylphenyl, benzyloxyphenyl, phenoxyphenyl and aralkyl, the substituents being selected from the series comprising halogen, cyano, Cl-C3-alkyl, Cl-C5-alkoxy, Cl-C5-halogenoalkyl, Cl-C3-alkylthio, Cl-C3-halogenoalkyl, Cl-C3-halogenoalkylthio, nitro and/or thiocyano, and X is oxygen or sulfur.
~Z3~7~l~
Subgroups which may be mentioned as enjoying a further preference are those comprising compounds of the formula I in which a) is 1,2,4-triazolyl or b) R2 is Cl-C6-alkyl or benzyl which is unsubstituted or substituted by halogen or c) Rl and R3 are hydrogen or Cl-C~-alkyl or d) R5 is phenyl which is substituted by halogen or e) X is oxy~en.
Within the subgroup b), preferred compounds are those in which R is tert.-butyl or i-propyl.
Within subgroup d), preferred compounds are those in which R5 is phenyl which is substituted in the 4~position by halogen.
Compounds whlch should be mentioned as a particularly preferred subgroup of compounds of the formula ~ are those in which Az is 1,2,4,-triazolyl, Rl and R3 are hydrogen or Cl-C4-alkyl, R2 is ter-t.-butyl or i-propyl, R5 lS phenyl which ~s substituted in the 4-position by halogen and X is oxygen.
The follo~ing are examples of preferred individual compounds of the formula I 1-(4-fluorophenoxy)-2-tert.-butyl-
2-hydroxy-3-fluoro-3-(lH-1,2,4,-trlazol-1-yl)-propane, 1-(4-fluorophenoxy~-2-tert -butyl-2-hydroxy-3-fluoro-3-methyl-3-(lX-1,2,4-triazol-1-yl)-propane, 1-(4-chlorophenoxy)-2-tert.-butyl-2-hydroxy-3-fluoro-3-(lH-1,2,4,-triazol-1-yl)-propane, 1-(4-chlorophenoxy)-2-tert.-butyl-2-hydroxy-3-fluoro-3-methyl-3-(lH-l, 2,4,-triazol-1-yl)-propane and 1-(4-methylphenoxy)-2-tert.-butyl-2-hydroxy-3-fluoro-3-methyl-3-(lH-1,2,4-triazol-1-yl)-propane.
~Z3~
In principle, unless expressly specified in an in-dividual case, one or more solvents or diluents, inert to the reaction, can be present when conducting any of the reactions herein described, Suitable examples are aliphatic and aromatic hydrocarbons, such as benzene, toluene, xylenes or petroleum ether; halogenated hydrocarbons, such as chlorobenzene, methylene chloride, ethylene chloride, chloroform, carbon tet-rachloride or tetrachloroethylene; ethers and ether-like compounds, such as dialkyl ethers (diethyl ether, diisoproply ether, tert.-butyl methyl ether etc.), anisole, dioxane or tetrahydrofuran; nitriles, such as acetonitrile or propionitrile;
N,N-dialkylated a~ides, such as dimethylformamide; dimethyl sulfoxide; ketones, such as acetone, diethyl ketone or methyl ethyl ~etone, and mixtures of such solvents with one another.
In some cases it can also be advantageous if the reaction is, or partial stages of a reaction are, carried out under an atmo-sphere of a protective gas and/or absolute solvents. Suitable protective gases are inert gases, such as nitrogen, helium or argon, or in certain cases also carbon dioxide.
It has no~ b~en found, surprisingly, that the new active substances of the formula I or compositions containing these active substances are especially distinguished by the fact that they intervene in a controlled manner in the metabolism of plants. This controlled intervention in the physiological processes of plant development makes it possible to use the active ~3~7~
substances of the formula I for various purposes, in particular for purposes associated with increasing the yield of useEul plants, facilitating harvesting and saving labour in the course of measures taken for crops of plants.
It has also heen found, surprisingly, that the acti~e substances of the formula I or corresponding compositions not only have advantageous growth-regulating properties, but also have a microbicidal spectrum which is very advantageous for practical requirements. A further field o-E use of compounds of the formula I is, therefore, the control of harmful micro-organisms, especially phytopathogenic fungi. Thus the compounds of the formula I posses a curative, preventive and systemic action for the protection of plants, in particular crop plants, which is very advantageous for practical requirements, without affecting these plants adversely.
The active substances of the formula I make lt possible to inhibit or destroy the microorganisms which occur on plants or parts of plants (fruit, flowers, foliage, stalks, tu~ers or roots~ of various useful crops, and parts of the plants which gro~ later also remain protected from microorganisms of this type.
The invention of the parent application also relates, therefore, to microbicidal compositions and to the use of the compounds of the formula I for controlling phytopathogenic microorganisms, in particular fungi which damage plants, and to ~3~7~l the prophylactic prevention of attack on plants.
In addition, the parent application also discloses the preparation of agrochemical compositions, which comprises mixing the active substance intimately with one or more suitable carriers or additives. It also includes a process for treating plants which is distinguished by the application of the compounds of the formula I and/or of the novel composi-tions.
The examples which follow serve to illustrate the preparation of the compounds of the present invention as well as the compounds of formula I of the parent application in greater detail without limiting the latter. Temperatures are quoted in degrees centigrade.
~Z3~17~l Preparation examples Example 1:
~5 ~H ~ CH~ - 0 ~ -F
1-(4-Fluorophenoxy)-2-tert.-butyl-2-hydroxy-3-fluoro-3-(1H-1 2 4-triazol-1-yl)-propane (Compound 5.6) , a) 1-Fluoro-1-(1H-1,2,4-triazol-1-yl)-3,3-dimethyl-2-butanone:
63.0 9 of 1-bromo-1-fluoro-3,3-dimethyl-2-butanone are added slowly to a mixture of 23.0 y of 1,2,4-triazole and 4~.2 g of potassium carbonate in 2~0 ml of ethyl methyl ketoneA The reaction mixture is stirred for 18 hours at 45-50C and is then filtered and evaporated. The residue is taken up in methylene chloride and washed with water.
Drying and evaporating the organic phase gives 50.0 g of 1-fluoro-1-(1H-1,2,4-triazol 1-yl)-3,3-dimethyl-2-butanone, melting point 54-55C.
b) 2-tert.-Butyl-2-~(1H-1,2,4-triazol-1-yl)-fluoromethyl]-ox;rane:
A mixture of 20 ~ of 1-fluoro-1-(1H-1~2,4~triazol-1-yl)-3,3-dimethyl-2-butanone, 13.5 9 of potassium tertiary buty~ate, Z4.0 9 of trimethylsulfoxonium iodide, 80 ml of tetrahydrofuran and 20 ml of dimethyl sulfoxide is stirred at 60C for 6 hours. The reaction m;xture is then taken up in ice water and extracted with ethyl acetate. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulfate and evaporated~
Crystall;sation from petroleum ether gives 6.9 9 of 2-tert.-butyl-2-~(1H-1,2,4~triazol-1-yl)~fluoromethyl]-oxirane, melting point 72-74C.
c) 3.0 g of 2-tert.-butyl-2-C(1H-1,2,4-triazol-1-yl)-fluoromethyl]-oxirane, 1.7 9 of 4-fluorophenol and 0.3 g of ~23~7~.
potassium p-fluorophenate in 10 ml of diethylene glycol di-methyl ether are stirred at 140C for 5 hours. A-Fter cooling, the mixture is taken up in ice wa-ter and extracted with ethyl acetate. The combined organic phases are washed with water, saturated sodium chloride solution and 2 ~ sodium hydroxide solution and again with saturated sodium chloride solution, dried over sodium sulfate and evaporated. Crystallisation from a 1:4 ether/hexane mixture gives 2.3 9 of 1-(4-fluoro-phenoxy)-2-tert.-butyl-2-hydroxy-3-fluoro-3-(1H-1,2,4-tria-zol-1-yl)~propane, melting point 89-90C.
Example 2:
CH - -CH
1-(4-Fluorophenoxy)-2-tert.-butyl-2-hydrOxy-3-fluoro-3-methyl-3-(1H-1,2,4-triaZol-1~yl)-propane (Compound 5.7).
a) 2-Fluoro-2-(1H-1,2,4-triazol-1-yl)-4,4-dimethyl-3-pentanone:
20.0 9 of 1-fluoro-1-(1H-1~2,4-triazol-1-yl)-3,3-dimethyl-2-butanone are added dropwise to a solution of 13.5 g of potassium tertiary butylate in 100 ml of tetrahydro-furan. After the m;xture has been stirred for D.5 hour, 15.6 g of methyl iodide are added dropwise and the mixture is st;rred for 18 hours at 60C. After coo~ing, the reaction mixture is taken up in ice water and extracted with ethyl acetate. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulfate and evaporated. Distillation of the oily residue gives 14.0 9 of 2-fluoro-2-(1H-1,2,4-triazol-1-yl)-4,4-dimethyl-3-pentanone, boiling point 48-50C/O.û13 mbar.
b) 2-tert.-Butyl-2-[1-fluoro-1-(1H-1,2,4-triazol-1-yl)-ethyl]-oxirane:
12.0 9 of 2-fluoro-2-(1H-1,2,4-triazol-1-yl)-4,4-dimethyl-3-pentanone are added dropwise to a mixture of 13.2 9 ~23~7~.
of trimethylsulfoxonium iodide, 7.3 9 of potassium tertiarybutylate, 20 ml of dimethyl sulfox;de and 80 ml of tetrahydro-furan, and the reaction mixture is stirred for 18 hours at 80C. After cooling, the mixture is taken up ;n ice water and extracted with ethyl acetate. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulfate and evaporated. Dis-tillation of the oily residue gives 6 9 2-tert.-butyl~2-C1-fluoro-1-(1H-1,2,4-triazol-1-yl)-ethyl]-oxirane, boiling point 60-61C/0.013 mbar.
c) 6.0 g of 2-tert.-butyl-2-C1-fluoro-1-(1H-1,2,4-triazol-1-yl)-ethyl~-oxirane~ 3.1 9 of 4-fluorophenol and 0.4 9 of potassium p-fluorophenate in 20 ml of d;ethylene glycol dimethyl ether are heated at 140C for 6 hours. After cooling, the reaction mixture is taken up in ice water and extracted with ethyl acetate. The combined organic phases are washed successively with water, saturated sod;um chlor;de solut;on, Z N sodium hydroxide solution, water and saturated sodium chlor;de solution, dried over sodium sulfate and evaporated. Chromatography over silica gel using a 4:1 hexane/ethyl acetate mixture gives 1.6 9 of 1-(4-fluoro-phenoxy~-2-tert.-butyl-2-hydroxy-3-fluoro-3-methyl-3-(1H-1,2,4~triazol-1-yl)-propane as a mixture of diastereomers, melt;ng point 90-93C~
The compounds isted in the follo~ing ta~les are prepared analogously.
71~ . .
Table 1 :
.~ F R
~CH2 No . R R2 Phys i ca l data .__ .. . ~ ._ ._ ___
~Z3~
In principle, unless expressly specified in an in-dividual case, one or more solvents or diluents, inert to the reaction, can be present when conducting any of the reactions herein described, Suitable examples are aliphatic and aromatic hydrocarbons, such as benzene, toluene, xylenes or petroleum ether; halogenated hydrocarbons, such as chlorobenzene, methylene chloride, ethylene chloride, chloroform, carbon tet-rachloride or tetrachloroethylene; ethers and ether-like compounds, such as dialkyl ethers (diethyl ether, diisoproply ether, tert.-butyl methyl ether etc.), anisole, dioxane or tetrahydrofuran; nitriles, such as acetonitrile or propionitrile;
N,N-dialkylated a~ides, such as dimethylformamide; dimethyl sulfoxide; ketones, such as acetone, diethyl ketone or methyl ethyl ~etone, and mixtures of such solvents with one another.
In some cases it can also be advantageous if the reaction is, or partial stages of a reaction are, carried out under an atmo-sphere of a protective gas and/or absolute solvents. Suitable protective gases are inert gases, such as nitrogen, helium or argon, or in certain cases also carbon dioxide.
It has no~ b~en found, surprisingly, that the new active substances of the formula I or compositions containing these active substances are especially distinguished by the fact that they intervene in a controlled manner in the metabolism of plants. This controlled intervention in the physiological processes of plant development makes it possible to use the active ~3~7~
substances of the formula I for various purposes, in particular for purposes associated with increasing the yield of useEul plants, facilitating harvesting and saving labour in the course of measures taken for crops of plants.
It has also heen found, surprisingly, that the acti~e substances of the formula I or corresponding compositions not only have advantageous growth-regulating properties, but also have a microbicidal spectrum which is very advantageous for practical requirements. A further field o-E use of compounds of the formula I is, therefore, the control of harmful micro-organisms, especially phytopathogenic fungi. Thus the compounds of the formula I posses a curative, preventive and systemic action for the protection of plants, in particular crop plants, which is very advantageous for practical requirements, without affecting these plants adversely.
The active substances of the formula I make lt possible to inhibit or destroy the microorganisms which occur on plants or parts of plants (fruit, flowers, foliage, stalks, tu~ers or roots~ of various useful crops, and parts of the plants which gro~ later also remain protected from microorganisms of this type.
The invention of the parent application also relates, therefore, to microbicidal compositions and to the use of the compounds of the formula I for controlling phytopathogenic microorganisms, in particular fungi which damage plants, and to ~3~7~l the prophylactic prevention of attack on plants.
In addition, the parent application also discloses the preparation of agrochemical compositions, which comprises mixing the active substance intimately with one or more suitable carriers or additives. It also includes a process for treating plants which is distinguished by the application of the compounds of the formula I and/or of the novel composi-tions.
The examples which follow serve to illustrate the preparation of the compounds of the present invention as well as the compounds of formula I of the parent application in greater detail without limiting the latter. Temperatures are quoted in degrees centigrade.
~Z3~17~l Preparation examples Example 1:
~5 ~H ~ CH~ - 0 ~ -F
1-(4-Fluorophenoxy)-2-tert.-butyl-2-hydroxy-3-fluoro-3-(1H-1 2 4-triazol-1-yl)-propane (Compound 5.6) , a) 1-Fluoro-1-(1H-1,2,4-triazol-1-yl)-3,3-dimethyl-2-butanone:
63.0 9 of 1-bromo-1-fluoro-3,3-dimethyl-2-butanone are added slowly to a mixture of 23.0 y of 1,2,4-triazole and 4~.2 g of potassium carbonate in 2~0 ml of ethyl methyl ketoneA The reaction mixture is stirred for 18 hours at 45-50C and is then filtered and evaporated. The residue is taken up in methylene chloride and washed with water.
Drying and evaporating the organic phase gives 50.0 g of 1-fluoro-1-(1H-1,2,4-triazol 1-yl)-3,3-dimethyl-2-butanone, melting point 54-55C.
b) 2-tert.-Butyl-2-~(1H-1,2,4-triazol-1-yl)-fluoromethyl]-ox;rane:
A mixture of 20 ~ of 1-fluoro-1-(1H-1~2,4~triazol-1-yl)-3,3-dimethyl-2-butanone, 13.5 9 of potassium tertiary buty~ate, Z4.0 9 of trimethylsulfoxonium iodide, 80 ml of tetrahydrofuran and 20 ml of dimethyl sulfoxide is stirred at 60C for 6 hours. The reaction m;xture is then taken up in ice water and extracted with ethyl acetate. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulfate and evaporated~
Crystall;sation from petroleum ether gives 6.9 9 of 2-tert.-butyl-2-~(1H-1,2,4~triazol-1-yl)~fluoromethyl]-oxirane, melting point 72-74C.
c) 3.0 g of 2-tert.-butyl-2-C(1H-1,2,4-triazol-1-yl)-fluoromethyl]-oxirane, 1.7 9 of 4-fluorophenol and 0.3 g of ~23~7~.
potassium p-fluorophenate in 10 ml of diethylene glycol di-methyl ether are stirred at 140C for 5 hours. A-Fter cooling, the mixture is taken up in ice wa-ter and extracted with ethyl acetate. The combined organic phases are washed with water, saturated sodium chloride solution and 2 ~ sodium hydroxide solution and again with saturated sodium chloride solution, dried over sodium sulfate and evaporated. Crystallisation from a 1:4 ether/hexane mixture gives 2.3 9 of 1-(4-fluoro-phenoxy)-2-tert.-butyl-2-hydroxy-3-fluoro-3-(1H-1,2,4-tria-zol-1-yl)~propane, melting point 89-90C.
Example 2:
CH - -CH
1-(4-Fluorophenoxy)-2-tert.-butyl-2-hydrOxy-3-fluoro-3-methyl-3-(1H-1,2,4-triaZol-1~yl)-propane (Compound 5.7).
a) 2-Fluoro-2-(1H-1,2,4-triazol-1-yl)-4,4-dimethyl-3-pentanone:
20.0 9 of 1-fluoro-1-(1H-1~2,4-triazol-1-yl)-3,3-dimethyl-2-butanone are added dropwise to a solution of 13.5 g of potassium tertiary butylate in 100 ml of tetrahydro-furan. After the m;xture has been stirred for D.5 hour, 15.6 g of methyl iodide are added dropwise and the mixture is st;rred for 18 hours at 60C. After coo~ing, the reaction mixture is taken up in ice water and extracted with ethyl acetate. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulfate and evaporated. Distillation of the oily residue gives 14.0 9 of 2-fluoro-2-(1H-1,2,4-triazol-1-yl)-4,4-dimethyl-3-pentanone, boiling point 48-50C/O.û13 mbar.
b) 2-tert.-Butyl-2-[1-fluoro-1-(1H-1,2,4-triazol-1-yl)-ethyl]-oxirane:
12.0 9 of 2-fluoro-2-(1H-1,2,4-triazol-1-yl)-4,4-dimethyl-3-pentanone are added dropwise to a mixture of 13.2 9 ~23~7~.
of trimethylsulfoxonium iodide, 7.3 9 of potassium tertiarybutylate, 20 ml of dimethyl sulfox;de and 80 ml of tetrahydro-furan, and the reaction mixture is stirred for 18 hours at 80C. After cooling, the mixture is taken up ;n ice water and extracted with ethyl acetate. The combined organic phases are washed with water and saturated sodium chloride solution, dried over sodium sulfate and evaporated. Dis-tillation of the oily residue gives 6 9 2-tert.-butyl~2-C1-fluoro-1-(1H-1,2,4-triazol-1-yl)-ethyl]-oxirane, boiling point 60-61C/0.013 mbar.
c) 6.0 g of 2-tert.-butyl-2-C1-fluoro-1-(1H-1,2,4-triazol-1-yl)-ethyl~-oxirane~ 3.1 9 of 4-fluorophenol and 0.4 9 of potassium p-fluorophenate in 20 ml of d;ethylene glycol dimethyl ether are heated at 140C for 6 hours. After cooling, the reaction mixture is taken up in ice water and extracted with ethyl acetate. The combined organic phases are washed successively with water, saturated sod;um chlor;de solut;on, Z N sodium hydroxide solution, water and saturated sodium chlor;de solution, dried over sodium sulfate and evaporated. Chromatography over silica gel using a 4:1 hexane/ethyl acetate mixture gives 1.6 9 of 1-(4-fluoro-phenoxy~-2-tert.-butyl-2-hydroxy-3-fluoro-3-methyl-3-(1H-1,2,4~triazol-1-yl)-propane as a mixture of diastereomers, melt;ng point 90-93C~
The compounds isted in the follo~ing ta~les are prepared analogously.
71~ . .
Table 1 :
.~ F R
~CH2 No . R R2 Phys i ca l data .__ .. . ~ ._ ._ ___
3.1 H C4Hg-tm~p. 72-74C
3.2 X C3H7-i 3.3 CH3 C4Hg-tb.p. 6o-6loc~
0,013 mtar 3.4 CH3 3 7 3.5 H 4-cl-c6H4-cH
3.6 H 4-F-C6H4-CX2-3.7 C2H5 4 9 . .
3.8 6 5 2 4 9 . .
3.9 4-cl-c6u4-cH2- C4Hg-t 3.10 ¦ 4-F-C H -CH C4Hq~t 3.11 ¦ C3H7~n C4Hg-t Table 2 :
~- ~ F R
~ / ~ \0/ 2 No. Rl R2 Physical data .
3.2 X C3H7-i 3.3 CH3 C4Hg-tb.p. 6o-6loc~
0,013 mtar 3.4 CH3 3 7 3.5 H 4-cl-c6H4-cH
3.6 H 4-F-C6H4-CX2-3.7 C2H5 4 9 . .
3.8 6 5 2 4 9 . .
3.9 4-cl-c6u4-cH2- C4Hg-t 3.10 ¦ 4-F-C H -CH C4Hq~t 3.11 ¦ C3H7~n C4Hg-t Table 2 :
~- ~ F R
~ / ~ \0/ 2 No. Rl R2 Physical data .
4.1 H C4Hg-t 4.2 H 3 7 4.3 CH3 C4Hg-t 4.4 CH3 C3H7~
4.5 H 4-cl-c4H6-cH
4.6 CH3 4 6 H2 4.7 C2H5 4 9 .
~:3~
Formulation examples Example 3 Examp es of formulations of liquid active substances of the formula I (% = per cent by weight) _ a) Emulsion concentrates a) b) c) Active substance 20% 40% 50%
Ca dodecylbenzenesulfonate 5% 8% 5.8%
Castor oil polyethylene glycol ether (36 moles of E0)5% - -Tributylphenol polyethylene glycol ether (30 moles of E0) - 12% 4.2%
Cyclohexanone - 15%20~
Mixed xylenes 70% 25%20%
Emulsions of any desired concentration can be pre-pared from such concentrates by dilution with water.
b3 Solutions a) b) c) d) Active substance 80% 10% 5% 95~.
Ethylene glycol monomethyl ether 20% - - -Polyethylene glycol ilW 400 - 70%
N-~lethyl-2-pyrrolidone - 20%
Epoxidised coconut oil - - 1% 5,0' Petroleum ether (boiling -- range 160-190C) - - 94%
The solutions are suitable for application ;n the form of very fine drops.
c) Granules a) b) Active substance 5% 10%
Kaol;n 94%
Highly disperse silica 1%
Attapulgite - 90%
The active substance is dissolved in methylene chloride, the solution is sprayed onto the carrier and the solvent is then removed by evaporation in vacuo~
d) Dusts a) b) Active substance 2% 5%
Highly disperse silica 1% 5%
Talc 97%
Kaol;n - 90%
Ready-to-use dusts are obtained by mixing the car-riers intimately with the active substance.
Example 4:
Examples of formulations of solid active substances of the .. . .
formula I (% = per cent by weight) _ a) Wettable powders a) b) Active substance 20% 60%
Na ligninsulfonate 5% 5%
Na laurylsulfate 3%
Na diisobutylnaphthalene-sulfonate - 6%
Octylphenol polyethylene g~ycol ether (7-8 moles of EO) - 2%
H;ghly disperse silica 5% 27%
Kaolin 67%
The active substance is thoroughly mixed with the adjuvants, and the mixture is thoroughly ground in a suit-able mill. This gives wettable powders which can be dilu-ted with water to give suspensions of any desired concen-tration.
~) Emulsion concentrate Active substance 10~, Octy~pheno~ po~yethylene gLycol ether (4-5 moles of EG) 3%
Ca dodecylbenzenesulfonate 3%
Castor oil polyglycol ether t36 moles of EO) 4%
Cyclohexanone 30%
Mixed xylenes 50%
Emulsions of any desired concentration can be pre-pared from this concentrate by dilution with water.
~3~7:~
c) Dusts a) b) Active substance 5% 8%
Talc 95%
Kaolin - 92%
Ready-to use dusts are obtained by mixing the act-ive substance with the carrier and grinding the mixture on a suitable mill.
d) Extruder granules Active substance 10%
Na ligninsulfonate2%
Carboxymethylcellulose 1%
~aolin 87%
The active substance is mixed with the adjuvants, and the mixture is ground and moistened with water. This mixture is extruded and then dried in a stream of air.
e) Coated granules Active substance 3%
Polyethylene glycol (MW 200) 3%
Kaolin 94%
The active substance is finely ground and applied uniformly, in a mixer, to the kaolin, which has been mois-tened with polyethylene glycol. Dust-free coated granules are obtained in this way.
f) Suspension concentrate Active substance 40%
Ethylene glycol 10~
Nonylphenol polyethylene glycol ether (15 moles of E0) 6%
Na l;gninsulfonate10~
Carboxymethylcellulose 1%
37% aqueous formaldehyde solution 0.2%
Sil;cone oil in the form of a 75% aqueous emulsion 0 ~%
~ater 32%
The active substance is finely ground and intimately ~z;~
mixed with the adjuvants. This gives a suspension concen-trate from which suspensions of any desired concentration can be prepared by dilution with water.
Biological example Example 5: Action against Puccinia graminis on wheat a) Residual protective action 6 days after being sown, wheat plants are sprayed with a spray liquor (0,06% of active substance) prepared from a wettable powder of the active substance. After 24 hours, the treated plants are infested with a uredospore suspension of the fungus. After being incubated for 48 hours at 95-100%
relative humidity and approx. 20C, the infested plants are placed in a greenhouse at appxox. 22C. Development of rust pustules is assessed 12 days after infestation.
b) Systemic action
4.5 H 4-cl-c4H6-cH
4.6 CH3 4 6 H2 4.7 C2H5 4 9 .
~:3~
Formulation examples Example 3 Examp es of formulations of liquid active substances of the formula I (% = per cent by weight) _ a) Emulsion concentrates a) b) c) Active substance 20% 40% 50%
Ca dodecylbenzenesulfonate 5% 8% 5.8%
Castor oil polyethylene glycol ether (36 moles of E0)5% - -Tributylphenol polyethylene glycol ether (30 moles of E0) - 12% 4.2%
Cyclohexanone - 15%20~
Mixed xylenes 70% 25%20%
Emulsions of any desired concentration can be pre-pared from such concentrates by dilution with water.
b3 Solutions a) b) c) d) Active substance 80% 10% 5% 95~.
Ethylene glycol monomethyl ether 20% - - -Polyethylene glycol ilW 400 - 70%
N-~lethyl-2-pyrrolidone - 20%
Epoxidised coconut oil - - 1% 5,0' Petroleum ether (boiling -- range 160-190C) - - 94%
The solutions are suitable for application ;n the form of very fine drops.
c) Granules a) b) Active substance 5% 10%
Kaol;n 94%
Highly disperse silica 1%
Attapulgite - 90%
The active substance is dissolved in methylene chloride, the solution is sprayed onto the carrier and the solvent is then removed by evaporation in vacuo~
d) Dusts a) b) Active substance 2% 5%
Highly disperse silica 1% 5%
Talc 97%
Kaol;n - 90%
Ready-to-use dusts are obtained by mixing the car-riers intimately with the active substance.
Example 4:
Examples of formulations of solid active substances of the .. . .
formula I (% = per cent by weight) _ a) Wettable powders a) b) Active substance 20% 60%
Na ligninsulfonate 5% 5%
Na laurylsulfate 3%
Na diisobutylnaphthalene-sulfonate - 6%
Octylphenol polyethylene g~ycol ether (7-8 moles of EO) - 2%
H;ghly disperse silica 5% 27%
Kaolin 67%
The active substance is thoroughly mixed with the adjuvants, and the mixture is thoroughly ground in a suit-able mill. This gives wettable powders which can be dilu-ted with water to give suspensions of any desired concen-tration.
~) Emulsion concentrate Active substance 10~, Octy~pheno~ po~yethylene gLycol ether (4-5 moles of EG) 3%
Ca dodecylbenzenesulfonate 3%
Castor oil polyglycol ether t36 moles of EO) 4%
Cyclohexanone 30%
Mixed xylenes 50%
Emulsions of any desired concentration can be pre-pared from this concentrate by dilution with water.
~3~7:~
c) Dusts a) b) Active substance 5% 8%
Talc 95%
Kaolin - 92%
Ready-to use dusts are obtained by mixing the act-ive substance with the carrier and grinding the mixture on a suitable mill.
d) Extruder granules Active substance 10%
Na ligninsulfonate2%
Carboxymethylcellulose 1%
~aolin 87%
The active substance is mixed with the adjuvants, and the mixture is ground and moistened with water. This mixture is extruded and then dried in a stream of air.
e) Coated granules Active substance 3%
Polyethylene glycol (MW 200) 3%
Kaolin 94%
The active substance is finely ground and applied uniformly, in a mixer, to the kaolin, which has been mois-tened with polyethylene glycol. Dust-free coated granules are obtained in this way.
f) Suspension concentrate Active substance 40%
Ethylene glycol 10~
Nonylphenol polyethylene glycol ether (15 moles of E0) 6%
Na l;gninsulfonate10~
Carboxymethylcellulose 1%
37% aqueous formaldehyde solution 0.2%
Sil;cone oil in the form of a 75% aqueous emulsion 0 ~%
~ater 32%
The active substance is finely ground and intimately ~z;~
mixed with the adjuvants. This gives a suspension concen-trate from which suspensions of any desired concentration can be prepared by dilution with water.
Biological example Example 5: Action against Puccinia graminis on wheat a) Residual protective action 6 days after being sown, wheat plants are sprayed with a spray liquor (0,06% of active substance) prepared from a wettable powder of the active substance. After 24 hours, the treated plants are infested with a uredospore suspension of the fungus. After being incubated for 48 hours at 95-100%
relative humidity and approx. 20C, the infested plants are placed in a greenhouse at appxox. 22C. Development of rust pustules is assessed 12 days after infestation.
b) Systemic action
5 days after belng sown, wheat plants are watered with a s~ray liquox (0.006% of acti~e substance, based on the volume of soil) prepared from a wettable powder of the active substance. After 48 hours, the treate~ plants are in~ested with a uredospore suspension of the fungus. After being incubated for 48 hours at 95-100% relative humidity and approx.
20C, the infested plants are placed in a greenhouse at approx.
22C. Development of rust pustules is assessed 12 days after infestation.
Compounds from Table 1 have a good action aga;nst '7~
Puccinia fungi. Untreated, but infested, control plants show a 100% attack by Puccinia. Inter ali.a, compounds 5.6 and 5.7 inhibit attack by Puccinia to 0 to 5%.
20C, the infested plants are placed in a greenhouse at approx.
22C. Development of rust pustules is assessed 12 days after infestation.
Compounds from Table 1 have a good action aga;nst '7~
Puccinia fungi. Untreated, but infested, control plants show a 100% attack by Puccinia. Inter ali.a, compounds 5.6 and 5.7 inhibit attack by Puccinia to 0 to 5%.
Claims (4)
1. A fluoroazolyl methyl oxirane of the formula II
(II) wherein Az is 1,2,4-triazolyl, R1 is hydrogen, C1-C6-alkyl which is unsubstituted or substituted by halogen or cyano, or C1-C3-phenylalkyl which is unsubstituted or substituted by halogen, C1-C3-alkyl, C1-C3-alkoxy, C1-C3-halogenalkyl, nitro, cyano, carboxyl or C1-C6-alkoxycarbonyl, R2 is C1-C10-alkyl which is unsubstituted or substituted by C1-C3-alkoxy, phenyl or C1-C3-phenylalkyl, it being possible for the phenyl nuclei in turn to be unsubstituted or substituted by halogen, C1-C3-alkyl, C1-C3-alkoxy, C1-C3-halogenoalkyl, nitro, cyano, carboxyl or C1-C6-alk-oxycarbonyl.
(II) wherein Az is 1,2,4-triazolyl, R1 is hydrogen, C1-C6-alkyl which is unsubstituted or substituted by halogen or cyano, or C1-C3-phenylalkyl which is unsubstituted or substituted by halogen, C1-C3-alkyl, C1-C3-alkoxy, C1-C3-halogenalkyl, nitro, cyano, carboxyl or C1-C6-alkoxycarbonyl, R2 is C1-C10-alkyl which is unsubstituted or substituted by C1-C3-alkoxy, phenyl or C1-C3-phenylalkyl, it being possible for the phenyl nuclei in turn to be unsubstituted or substituted by halogen, C1-C3-alkyl, C1-C3-alkoxy, C1-C3-halogenoalkyl, nitro, cyano, carboxyl or C1-C6-alk-oxycarbonyl.
2. 2-tert.-Butyl-2- [(1H 1,2,4-triazol-1-yl)-fluoro-methyl] -oxirane according to claim 1.
3. 2-tert.-Butyl-2-[-fluoro-1-(1H-1,2,4-triazol-1-yl)-ethyl]-oxirane according to claim 1.
4. A process for the preparation of a compound of for-mula II according to claim 1, which process comprises re-acting a ketone of the formula V
wherein Az, R1 and R2 are as defined in claim 1, in the presence of a strong base in dimethyl sulfoxide, N,N-di-methylformamide, N,N-dimethylacetamide, acetonitrile, benzo-nitrile, N-methylpyrrolidone, N-methylpiperidone, benzene, toluene, xylene, hexane, cyclohexane, chlorobenzene or ni-trobenzene or in a mixture of these solvents with one another, with dimethylsulfonium methylide, dimethyloxosul-fonium methylide, trimethylsulfonium iodide or trimethyl-oxosulfonium iodide.
wherein Az, R1 and R2 are as defined in claim 1, in the presence of a strong base in dimethyl sulfoxide, N,N-di-methylformamide, N,N-dimethylacetamide, acetonitrile, benzo-nitrile, N-methylpyrrolidone, N-methylpiperidone, benzene, toluene, xylene, hexane, cyclohexane, chlorobenzene or ni-trobenzene or in a mixture of these solvents with one another, with dimethylsulfonium methylide, dimethyloxosul-fonium methylide, trimethylsulfonium iodide or trimethyl-oxosulfonium iodide.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000524386A CA1231711A (en) | 1983-01-10 | 1986-12-02 | Fluoroazolyl methyl oxiranes |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH11283 | 1983-01-10 | ||
| CH112/83-4 | 1983-01-10 | ||
| CA000444679A CA1222518A (en) | 1983-01-10 | 1984-01-04 | Fluoroazolylpropane derivatives |
| CA000524386A CA1231711A (en) | 1983-01-10 | 1986-12-02 | Fluoroazolyl methyl oxiranes |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000444679A Division CA1222518A (en) | 1983-01-10 | 1984-01-04 | Fluoroazolylpropane derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1231711A true CA1231711A (en) | 1988-01-19 |
Family
ID=25670260
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000524385A Expired CA1231713A (en) | 1983-01-10 | 1986-12-02 | Fluoroazolyl ketones |
| CA000524386A Expired CA1231711A (en) | 1983-01-10 | 1986-12-02 | Fluoroazolyl methyl oxiranes |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000524385A Expired CA1231713A (en) | 1983-01-10 | 1986-12-02 | Fluoroazolyl ketones |
Country Status (1)
| Country | Link |
|---|---|
| CA (2) | CA1231713A (en) |
-
1986
- 1986-12-02 CA CA000524385A patent/CA1231713A/en not_active Expired
- 1986-12-02 CA CA000524386A patent/CA1231711A/en not_active Expired
Also Published As
| Publication number | Publication date |
|---|---|
| CA1231713A (en) | 1988-01-19 |
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| Date | Code | Title | Description |
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| MKEX | Expiry |