Note: Descriptions are shown in the official language in which they were submitted.
~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.
R3
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)
1 1
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.
-- 4 --
~;~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.
-- 5 --
~.~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
-- 7 --
~ ~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.
--10--
~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.
-12-
~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
-13-
~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
-14-
~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
-16-
~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:
- CU2 -
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
-17-
~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.
-18-
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
.
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
.
--19--
~: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%
- -20-
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.
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~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
--22--
~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
-23-
'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%.
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