Note: Descriptions are shown in the official language in which they were submitted.
10940~9
BACKGROUND OF THE INVENTION
.
In U.S. Pat. No. 3,575,999 there are described 1-(~ aryl)-
ethyl-imidazole ketals having antibacterial and antifungal prop-
erties.
In the prior art there may also be found a number of
triazole derivatives, some of which are described as fungicides
or growth regulators.
Among other differences the compounds of this invention
differ from the triazole derivatives of the prior art by the
nature of the side chain which is attached to the triazole ni-
trogen atom.
The closest prior art on triazole derivatives is tenta-
tively represented by the following references:
Neth. Pat. Appln. 69.13.028; and
Fr. 2.200.012 - Derwent Week V25 - Pharm. p. 7.
DESCRIPTION OF THE PREFERRED EMBODIMENTS:
This invention relates to a novel group of chemical com-
pounds and more particularly to lH-l, 2, 4-triazole derivatives
having the formula:
I _ N
N`N J
CH2 - C - Ar (I)
O /0
~094079
wherein:
Z is an alkylene selected from the group consisting of
-CH2-CH2-~ -CH2-CH2-CH2-- -CH-IH- and -CH2-CH-
H3C CH3 alkyl
wherein said alkyl has from 1 to about 10 carbon atoms;
and
Ar is a member selected from the group consisting of phenyl,
substituted phenyl, thienyl, halothienyl, naphthyl and
fluorenyl,
wherein "substituted phenyl" has the meaning of a
phenyl radical having thereon from 1 to 3 substituents
selected independently from the group consisting of
halo, loweralkyl, loweralkyloxy, cyano and nitro.
~he thereapeutically active acid addition salts of the
foregoing compound (I) are also embraced within the scope of
this inven~ion.
As used in the foregoing definition of Z, the term
"alkyl" is meant to include straight and branch chained hydro-
carbon radicals having from 1 to about 10 carbon atoms, such as,
for example, methyl, ethyl, l-methylethyl, propyl,
l,l-dimethylethyl, butyl, pentyl, hexyl, heptyl, octyl, decyl
and the like; as used herein "loweralkyl" may be straight or
branch chained saturated hydrocarbons having from 1 to about 6
carbon atoms, such as, for example, methyl, ethyl, propyl,
l-methylethyl, butyl, l,l-dimethylethyl, pentyl, hexyl and the
like alkyls; and the term "halo" is generic ~o halogen atoms of
atomic weight less than 127; i.e., fluoro, chloro, bromo and
iodo.
1094079
The ketals of formula (I) are readily obtained by react-
ing lH-l, 2, 4-triazole (II), previously converted into a metal
salt thereof, such as, for example, by treatment with an alkali
metal alkoxide, preferabl~ sodium methoxide, with a halide of
formula (III)
Y-CH2 - C - Ar
O O
\ / (III)
0
wherein Ar and Z are as previously defined and Y is halo, pre-
ferably bromo. The reaction of lH-l, 2, 4-triazole (II) with
(III) is preferably carried out in an appropriate polar reaction-
inert organic solvent, such as, for example, N,N-dimethylforma-
mide, N,N-dimethylacetamide, acetonitrile, benzonitrile and the
like. Such solvents may be used in combination with other reac-
tion-inert organic solvents, such as, for example, benzene,
methylbenzene, dimethylbenzene and the like. When Y stands for
bromo or chloro, the addition of an alkali metal iodide, such
as, for example, sodium- or potassium iodide is appropriate.
50mewhat elevated temperatures are appropriate to enhance the
rate of the reaction and most preferably the reaction is carried
out at the reflux temperature of the reaction mixture.
The resulting ketal of formula (I) is then isolated from
the reaction mixture by conventional means and, if desired,
further purified according to common purification procedures
such as, for example, crystallization, extraction, trituration,
chromatography, etc.
The foregoing procedure is further illustrated by the
following schematic representation:
--3--
1094079
Y-CH2 - C -Ar
N O O (III)
I
N ~ NaOMe
~N/ > ~(I)
DMF , NaI
(II)
The thus-obtained compounds of formula (I), in base form, -
may be converted to their therapeutically useful acid addition
salts by reaction with an appropriate acid, as, for example,
an inorganic acid such as hydrohalic acid, i.e. hydrochloric,
hydrobromic or hydroiodic acid; sulfuric, nitric or thiocyanic
acid; a phosphoric acid; an organic acid such as acetic,
propanoic, hydroxyacetic, ~-hydroxypropanoic, 2-oxopropanoic,
ethanedioic, propanedioic, l,4-butanedioic, (Z)-2-butenedioic,
(E)-2-butenedioic, ~-hydroxy-1,4-butanedioic, 2,3-dihydroxy-1,
4-butanedioic, 2-hydroxy-1,2,3-propanetricarboxylic, benzoic,
3-phenylpropenoic, ~-hydroxybenzeneacetic, methanesulfonic,
ethanesulfonic, hydroxyethanesulfonic, 4-methylbenzenesulfonic,
~-hydroxybenzoic, 4-amino-2-hydroxybenzoic, 2-phenoxybenzoic
or 2-acetyloxybenzoic acid. The salts are in turn converted
to the corresponding free bases in the usual manner, e.g., by
reaction with alkali suGh as sodium or potassium hydroxide.
The starting materials of formula (III), a number of
which are known compounds, may be prepared according to known
prccedures. ~uch compounds wherein Z is selected from the group
consisting of -CH2-CH2-, -CH(CH3)-CH2-, -CH(CH3)-CH(CH3) - and
-CH2-CH2-CH2- and methods of preparing the same are described
in U.S. Pat. No. 3,575,999. In general the compounds of formula
(III) may be prepared by the ketalization of an appropriate
ketone of formula (IV) wherein Ar and Y are as previously defined,
109~079
with an appropriate diol of formula (V) following known ketali-
zation procedures as are described in the literature [see e.g.
Synthesis, 1974 (1), 231].
In a preferred method both reactants are refluxed togeth-
er for several hours with azeotropic water removal in an appro-
priate organic solvent, preferably in the presence of a simple
alcohol, such as, for example, ethanol, propanol, butanol,
pentanol and the like, and in the presence of an appropriate
strong acid such as, for example, 4-methylbenzenesulfonic acid.
Suitable organic solvents which may be used therefore include,
for example, aromatic hydrocarbons such as benzene, methylben-
zene, dimethylbenzene and the like and saturated hydrocarbons,
such as cyclohexane.
ll 4-methylbenzenesulfonic acid
Ar-C-CH2Y + HO-Z-OH butanol , (III)
benzene
(IV) (V)
The ketones of formula (IV) are generally known and may
be prepared following methodologies known to those skilled in
the art.
From formula (I) it is evidence that several of the com-
pounds of this invention have asymmetric carbon atoms within
their structure and consequently they may exist under different
stereochemical optical isomeric forms. More particularly, when
an alkylgroup is present in the 4-position of the dioxolane-
nucleus, the carbon atom to which it is attached and the carbon
atom in the 2-position of the dioxolanenucleus are asymmetric.
The stereochemical optical isomers of compounds of formula (I)
may be separated and isolated following methodologies known to
those skilled in the art. Said isomers are intended to be with-
in the scope of this invention.
1094079
The compounds of formula (I) and the acid addition salts
thereof are useful agents in combatting fungi and bacteria. As
such the compounds of this invention are valuable in the treat-
ment of plants, animals and human beings suffering from patho-
genic micro-organisms and in the destruction of microorganism on
materials.
The compounds of this invention are very potent agri-
cultural fungicides. They are very active against a wide vari-
ety of fungi such as, for example, those responsible for the
occurence of powdery mildew on different plant species, e.g.,
Erysiphe graminis, Erysiphe polygoni, Erysiphe cichoracearum,
Erysiphe polyphaga, Podosphaera leuchotricha, Sphaerotheca
pannosa, Sphaerotheca mors-uvae, Uncinula necator, etc., and
other fungi, such as, for example, Venturia inaequalis,
Colletotrichum lindemuthianum, Fusarium oxysporum, Alternaria
tenuis, Thielaviopsis basicola, Helminthosporium gramineum,
Penicillium digitatum, etc.,
They are especially useful in view of their prophylactic
as well as curative and systemic action. Their potent antifun-
gal action against phytopathogenic fungi is more clearly illus-
trated by the results obtained in the following experiments.
In several of these experiments the compound 1-~2-(2,4-
dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-triazole,
~I-a), was used as a representative member of the compounds of
formula (I).
1C~9 ~079
~N ) Cl
GH2 -f ~ Cl
1
(I-a)
It is understood that the compounds for which experimen-
tal test results are presented are not given for the purpose of
limiting the invention thereto but only to exemplify the strong
antifungal activity of all the compounds within the scope offormula (I).
A. Prophylactic action of compounds of formula (I)
against Erysiphe cichoracearum on cucumber upon foliar treatment.
Young cucumber plants, about 10 days old, were sprayed with an
aqueous solution containing 250, 100 or 10 ppm of the compound
to be tested while controls were kept untreated. After drying
of the plants, artificial infection with spores of Erysiphe
cichoracearum was carried out by slightly rubbing the plants
with a heavily infected leaf. At the 15th day after artificial
infection the degree of fungal attach was evaluated by counting
the number of spots per plants. The results given in table I
are mean values for 2 plants and expressed according to the
following score system~
O = O spots per plant.
1 = 1 to 5 spots per plant.
2 = 6 to 10 spots per plant.
3 = more than 10 spots per plant.
lOg4079
ABLE I: Prophylactic action of compounds (I) against Erysiphe
cichoracearum on cucumber plants upon foliar treatment.
~ N
N ~l
~N/
CH2 Ar
R ~
Base Antifungal score
Ar R or . 250 m 100 m 10 m
_, PP PP PP
2,4-(Cl)2-C6H3 H base _ 0 0
C6Hs H base _ 3
4-NO2-C6H4 H base 0 _
3-Cl-C6H4 H base _ 2
2-Cl-C6H4 H (COOH)2 - -
4-Br-C6H4 H base 0 _
2-Br-C6H4 H (COOH)2 - 2
3-OCH3-C6H4 H (COOH)2 1 _
2-CH3-C~H4 : H (COOH)2 ~
4-F-C6H4 H (COOH)2 -
4-CH3-C6H4 H (COOH)2 ~
4-Cl-C6H4 H (COOH)2.H2O _ 0
2-naphthyl H (COOH)2 -
2,5-(Cl)2 C6H3 H (COOH)2 ~
4-CN-C6H4 H (COOH)2 -
3,4-(C1)2-C6H3 H (COOH)2 - 3
2-OCH3-C6H4 H (COOH)2 1 _
2-thienyl H (COOH)2 - 2
2-fluorenyl H base 0 _
5-Cl-2-thienyl H base _ 2 _
1094079
. Ar ¦R Base Antii ung~l sc ore
Salt form 250ppm 100ppm 10ppn
3-Br,4-CH3~C6H3 H base 0 _ _ ¦
2-CH3,4-Br-C6H3 H base _ 2
2-CH3,4-Cl-C6H3 H base 0 _
3-Br-C6H4 . H base 2 _
4-I-C H4 H (COOH) 2 -
3, 5- (Cl) 2-C6H3 H (COOH) 2 - 2 _
2, 3-(Cl)2-c6H3 H (COOH)2 -
3-NO2-C6H4 H base 1 _
2,4- (Br) 2-C6H3 H (COOH)2 _ 1
2,4, 5- (Cl) 3 C6H2 H (COOH)2 -
2-Cl, 4-OCH3-C6H3 H (COOH)2 _ 2
2,4-(Cl)2-C6H3 CH3 HNO3 0 _
2~4-(cl)2-c6H3 C2H5 HNO3 _ 0 0
2,4-(Cl)2-C6H3 nC3H7 HNO3 _ 0 0
2,4-(Cl)2-C6H3 nC4Hg 11/2(COOH)2 _ 2
2,4-(Cl)2 C6H3 nC5Hll HNO3 ~ 0 0
2,4-(Cl)2-C6H3 nC6H13 HNO3 0 _
2,4-(Cl)2 C6 3 nc7Hl5 HNO3 _ 2
2,4-(Cl)2 C6H3 nC8H17 HNO3 0 _
109~079
A.l Prophylactic action against Erysiphe polyphaga on
cucumber upon foliar treatment.
Young cucumber plants in the one-leaf stage were sprayed with
an aqueous solution containing 500, 250 or 125 ppm of (I-a)
while controls were kept untreated. Artificial infection with
spores of Erysiphe polyphaga was carried out by slightly rub-
bing the plants with a heavily infected leaf on the 4th, 6th or
8th day after treatment. At the 18th and 34th day after treat-
ment, the percentage of leaf surface attacked by the fungus was
determined separately for the infected leaves and for the newly
developed leaves. The results given in Table I.l are mean
values for 5 plants and expressed in percent attack as compared
to untreated.
TABLE I.l Prophylactic activity of (I-a) against Erysiphe
polyphaga on cucumber upon foliar treatment.
Date of evalu- 18 days after 1 34 days after
ation treatment I treatment
Infected at j 1; 1
statad day af- 4 l 6 ¦ 8 4 6 8
ter treatment l l
Infected leaves l l - i 1 _ i
(a) or newly
developed leave ~ l
~b) a¦ b ¦ a¦ b¦ a b a¦ b a b a b
~ I _ ~ _
Concentr. of
(I-a~ in spray
solution ~
Untreated 100¦100¦100¦100¦100 100 100 100¦10 ¦ lOOllO0 100
500 ppm 0 0 ¦ 0 Ij 0 ¦ 0 0 0 0 1 0 l 0
250 ppm 0 ¦ Ij ¦ I ¦
125 ppm 0 I 0 ¦o ¦ 0 ¦ 0 I 0 I 0 ' 0 0 ¦o 0
--10--
109~079
B. Prophylactic action against Erysiphe graminis on
barley upon soil treatment.
Barley plants were treated by watering with 100 ml. per plant
of an aqueous solution containing 1.000, 100 or 10 ppm of (I-a).
Controls received the same volume of the solution containing no
(I-a). Natural infection, which normally occurs when the
plants are held in the glass-house in the vicinity of infected
plants, was evaluated 16 days after treatment by counting the
number of spots on the leaves. Per object 5 plants were used
and the results in Table II are mean values expressed in percent
attack as compared to the controls.
TABLE II: Prophylactic action of (I-a) against Erysiphe
graminis on barley upon soil treatment.
Dose in mg. (I-a)
% attack versus control
per plant
I
20Control 100
100 mg 0
10 mg 0
1 mg 53
C. Curative action against Erysiphe graminis on barley
upon foliar treatment.
Barley plants attacked by Erysiphe graminis were sprayed with
an aqueous solution containing (I-a) at the indicated concen-
tration. On the 16th day after treatment the number of spots30
per plant was determined. Per object 5 plants were used and
the xesults given in Table III are mean values expressed in per-
1094079
cent attack as compared to control.
TABLE III: Curative action of (I-a) against Erysiphe graminis
on barley upon foliar treatment.
Concentration of (I-a) % attack compared
in the spray-solution to control
Q 100
1,000 ppm 0
100 ppm 1~5
10 ppm 25 I
D. Prophylactic action of (I-a) against Podosphaera
leuchotricha on apple seedlings upon spraying.
Apple seedlings, one year old, were sprayed with an aqueous
solution containing (I-a) at the indicated concentration.
The plants were artificially infected as described in test "A"
with spores of Podosphaera leuchotricha 1 day after treatment
and incubated for 36 hours. The degree of fungal attack was
evaluated 25 days after treatment by counting the number of
spots. Per object 2 plants were used and the results given in
Table IV are mean values expressed in percent attack as com-
pared to control.
TABLE IV: Prophylactic action of (I-a) against Podosphaera
leucotricha on apple seedlings upon spraying.
- -- i
Concentration of (I-a) % attack compared¦
in spraying solution to control
_ -
O 100
100 ppm
3010 ppm 6
-12-
1~9~0'79
E. Activity against Thielaviopsis sp.
Slides of potato and leek, 5 mm. thick, were dipped in an aqueous
test solution, containing (I-a) at the stated concentration. Af-
ter dipping, the slides were placed on filter paper, in a large
plastic tray and the tray was covered with glass. Artificial
infection was carried out at the day of treament by spraying the
slides with a concentrated suspension of spores of Thielaviopsis
sp. and the slides were incubated at room temperature.
Fungal growth on the slides was evaluated 6 days after treatment
1~ - by estimating the surface attacked by the fungus. The results
giYen in Table V are expressed in percent attack as compared to
the control.
TABLE V: Activity of (I-a) against Thielaviopsis sp.
% attack compared
Concentration of (I-a) in to control
the test-solution in ppm I Potato Leek
o loo loo
1,000 O O
100 O O 1,
0 42.8
1 1 11 100 ',
The compounds of formula (I) are also very active against
a wide variety of fungi which are pathogenic to human beings and
animals. For example they are active against fungi such as
Microsporum canis, Trichophyton mentagrophytes, Trichophvton
rubrum, ~spergillus fumigatus, Phialophora verucosa, Cryptococcus
neoformans, Candida albicans, Candida tropicalis, etc. The e~-
cellent activitv against Candida albicans is more clearlv
demonstrated bv the results obtained in the following e~periments.
1094079
F. Activity of (T-a) against crop candidosis in turkeys.
Young turkeys (14 days old) were artificially infected by gavage
into the crop of a suspension containing 4.106 C.F.U. (colony
forming units) of Candida albicans.
After the infection the animals received either their normal diet
(control group) or a medicated food containing 125 ppm of (I-a).
Two weeks thereafter all turkeys were sacrificed, cultures were
made of the crop, and the number of candida colonies per gram of
crop were counted.
The results are summarized in Table VI.
TABLE VI: Number of colonies of Candida albicans per gram of
crop in turkeys treated with (I-a) - (125 ppm) or
placebo.
Treatment I Number of Number of Candida
the animal colonies per gram crop
I
Controls 1 3,520,000
2 84~,700
3 3,132,000
4 1,909,000
__ _ _ _ _ _ _ _ _ ___ _ _ _ _ _ _ _ _ _ _ _ _
(I-a) 1 0
(125 ppm) ¦ 23 l 247 200
As is shown by the results in Table VI, (I-a) at the
125 ppm level is highly effective against crop candidosis as
compared to the corresponding controls.
G. Activity of ~I-a) against vaginal candidosis in rats.
Female rats of 100 g. body weight were ovariectomized and
hysterectomized. About three weeks thereafter all animals re-
ceived a weekly subcutaneous injection of 100 mg. oestradiol
undecyiate and were infected intravaginally with a suspension
containing 8.105 C.F.~. of Candida albicans.
Groups of four rats were then orally treated for 14 cons~cutive
- 14 -
~Q'~079
days with either solvent (PEG 200) or (I-a). The administered
dose of the compound was 40 mg/kg orally. Vaginal smears were
taken from all animals at the end of the treatment period
(i.e. 14 days), cultivated on Sabouraud agar medium containing
Penicillin (20 I.U./ml) and Strepto~rcin (40 ~g,iml), and the
number of Candida colonies were counted thereafter.
Table VI~ summarizes the results obtained with (I-a) against
vaginal candidosis in rats.
TABLE VII: Number of animals per culture score
~Culture scoreXJ ¦
TreatmentNumber of Day after
animal`streatment O 1 21 3 4
Controls 414 0 0 0 1 3
(PEG 200)
(I-a) _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ ___
orally) 4 1 14 L ~ ~
X) culture score: 0 = no growth
1 = 1-25 colonies
2 = 26-100 colonies
3 = >100 colonies
4 = innumerable colonies
As is apparent from the results in Table VII, (I-a) is a very
potent agent against vaginal candidosis in rats.
H. Actlvity of (I-a) against systemic candidosis in
guinea pigs.
Adult male guinea pigs were intravenously infected with Candida
albicans, which induces a general systemic candidosis.
Afterwards groups of 7 guinea pigs were orally ~eated for 1~
consecutive da~s with eitn2r solvent (2E~ 200) o~ ~I-a). The
dose used ~-as ~0 ms~kg. l~ody weight.
- 15 -
`- 109~079
Four days after the last treatment day, all animals were sacri-
ficed, the kidneys removed, cultivated on Sabouraud agar medium
containing Penicillin (20 I.U~ml) and Streptomycin (40 ~g/ml)
and the number of isolated Candida albicans colonies per gram
kidney were counted. Table VIII shows the detailed results ob-
tained with (I-a) against systemic deep m~cosis in guinea pigs.
TABLE VIII:
Treatment ! Number of Number of Candida colonies
the animal per gram kidney
Controls 1 182
(PEG 200) 2 2,838
3 25,220
6 19,800
_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _
(I-a) 1 0
(40 mg/kg
orally) 2 18
3 0
S O
_
From the results in Table VIII it may be concluded that (I-a) is
an extremely potent agent against systemic deep mycosis in
guinea pigs .
Apart from their antimicrooial effects, tne compounds Qf
formula (I) possess valuable plant growth regulating properties.
Depending on different factors such as the species of the
plants under treatment and the dose of acti~e ingredient adminis-
tered, the obser~ed effect may he growth stimulatiQn as ~ell as
1C)~4079
growth inhibition, As such the compounds of this invention are
useful as plant growth regulators. More particularly they may
be used as plant growth inhibitors or retardants, especially as
inhibitors of sucker growth, e.g., on tobacco plants. Under
certain circumstances they may however also be used as plant
growth stimulators.
The plant growth regulating properties of the compounds
of formula (I), which are naturally intended to be within the
scope of this invention, are more clearly illustrated by the
results obtained in the following experiments, wherein the com-
pound (I-a) was used as a representative member of the compounds
of this invention. The results obtained with (I-a) are not
given for the purpose of limiting the invention thereto but
only in order to exemplify the useful plant growth regulating
properties of all the compounds within the scope of formula (I).
I. Growth regulating effect on tomato plants upon soil
treatment.
Young tomato plants 3.5 to 4 cm. high ~ere ~lanted in separate
pots. Each pot was watered with a test solution containing the
.. ... . . ..
2 indicated amount of (I-a). Growth was evaluated bv determining
the length and the weight of the plants 28 days after treatment.
The results siven in Table IX are mean values of five plants
expressed in percent as compared to the control plants.
TABLE IX: Gro~7th regulating effect of (I-a3 on tomato plants
upon soil treatment.
1~9~079
Dose of (I-a) Length of plants in % Weight of plants in %
in mg/plant I compared to control co~pared to control
I none 100 100
114 118
1 127 134
0.1 122 116
! _
J. Growth regulating effect on barley upon foliar
treatment.
Young barley plants in the 3-4 leaf-stage were sprayed with a
test solution containing (I-a) in the indicated concentration.
The effect on the growth of the plants is evaluated 24 days af-
ter treatment by determining the weight of the plants. The re-
sults given in Table X are mean values of ten plants expressed
in percent as compared to the controls.
TABLE X: Growth regulating effect of (I-a) on barley upon
foliar treatment.
Conc. of (I-a) in test Average weight of plants
solution in ppm in percent of control
none 100
125 126
60 116
K. Sucker growth control on tobacco plants.
Tobacco plants, var. "Xanthi" were raised in the greenhouse
and topped at the early button stage.
After 5 days, foliar spray treatment with an aqueous suspension
of compound (I-a) at rates equivalent of 3 and 1.5 kg. a.i./ha
was carried out.
Each treatment was replicated 3 times. i2 days after applica-
10~3-~079
tion, the subsequent sucker growth was assessed in comparison
to the topped and untreated check plants.
The recorded reductions of sucker growth were 100% at the 3.0
kg/ha rate and 90% at 1.5kg/ha.
L. Growth inhibition on soybean plants.
Soybean plants~ var. "Hark" were grown in pots in the growth
chamber at 23C, 20 000 Lux and a daylength of 14 hours.
After the 3rd trifoliate leaf had unfolded, the plants were
sprayed with an aqueous suspension of compound (I-a) at concen-
trations of 1000, 500, 100 and 50 ppm active ingredient.
The % growth inhibition of the treated plants in comparison to
the check was assessed after 14 days.
The following results were obtained:
Treatment % growth inhibition
(I-a) 1000 ppm a.i. 70%
500 ppm a.i. 40%
100 ppm a.i. 25%
50 ppm a.i. 0%
chec~ 0%
_ ,
At the concentration of 1000 ppm, a more intensive green colour
of the foliage was observed.
In view of the aforementioned antifungalr antibacterial
and growth-regulating activities this invention provides valu-
able ~ompositions comprising the subject ketals tI) or the
acid aadition salts thereof as the active ingredient in a sol-
vent or a solid, semi-solid or liquid diluent or carrier, and,
in addlt~on, it provides an effective method of comba~ing fung-
~)'3i~079
us or bacterlal growth by use of an effective antifungal or
antibacterial amount of such ketals (I) or salts thereof.
The subject compounds can be used in suitable solvents or
diluents, in the form of emulsions, suspensions, dispersions
or ointments, on suitable solid or semi-solid carrier substances,
in ordinary or synthetic soaps, detergents or dispersion media,
if desired, together with other compounds having arachnicidal,
insecticidal, ovicidal, fungicidal and/or bactericidal effects,
or together with inactive additives.
Solid carrier substances which are suitable for the
preparation of compositions in powder form include various inert,
porous and pulverous distributing agents of inorganic or organic
nature, such as, for example, tricalcium phosphate, calcium
carbonate, in the form of prepared chalk or ground limestone,
kaolin, bole, bentonite, talcum, kieselguhr and boric acid;
powdered cork, sawdust, and other fine pulverous materials of
vegetable origin are also suitable carrier substances.
The active ingredient is mixed with these carrier sub-
stances, for example, by being ground therewith; alternatively,
the inert carrier substance is impregnated with a solution of
the active component in a readily volatile solvent and the sol-
vent is thereafter eliminated by heating or by filtering with
suction at reduced pressure. By adding wetting and/or dispers-
ing agents, such pulverous preparations can also be made readily
wettable with water, so that suspensior,s are obtained.
10~4079
Inert solvents used for the production of liquid
preparations should preferably not be readily inflammable E
and should be as far as possible odorless and as far as possible
non-toxic to warm-blooded animals or plants in the relevant
8urroundings. Solvents suitable for this purpose are high-boiling
oils, for example, of vegetable origin, and lower-boiling solvents
with a flash point of at least 30C., such as, for example, polyethylene glycol
isopropanol, dimethylsulfoxide, hydrogenated naphthalenes and
aL~cylated naphtnalenes. It is, of course, also possible to use
mixtures of solvents. Solutions can be prepared in the usual way,
if nece9sary, with assistance of solution promotors. Other liquid
forms which can be used consist of emulsions or suspensions of
the active compound in water or suitable inert solvents, or also
concentrates for preparing such emulsions, which can be directly
adjusted to the required concentration. For this purpose, the
active ingredient is, for example, mixed with a dispersing or
emulsifying agent. The active component can also be dissolved
or dispersed in a suitable inert solvent and mixed simultaneously
or subsequently with a dispersing or emulsifying agent.
.
It is also possible to use 8emi-solid carrier substances
: of a cream ointment, paste or waxlike nature, into which the
active component can be incorporated, if necessar, with the aid
of solution promotors and/or emulsifiers. ~aselin~ and other
cream bases are examples of semi-solid carrier substances.
- Furthermore, it is possible for the active component
to be used in the form of aerosols. For this purpose, the active
-21-
;.
'i
I_
10~4079
component is dissolved or dispersed, if necessary, with the aid
of suitable inert solvents as carrier liquids, such as
difluorodichloromethane, which at atmospheric pressure boils at
a temperature lower than room temperature, or in other volatile
solvents. In this way, solutions under pressure are obtained
which, when sprayed, yield aerosols which are particularly suit-
able for controlling or conbatting fungi and bacteria, e.g.,
in closed chambers and storage rooms, and for application to
vegetation for eradicating or for preventing infections by
fungi or bacteria.
The subject compounds and compositions thereof can be
applied by conventional methods. For example, a fungus or
bacterial growth or a material to be treated or to be protected
against attac~ by fungus or bacterium can be treated with the
subject compounds and the compositions thereof by dusting,
sprinkling, spraying, brushing, dipping, smearing, impregnating
or other suitable means.
When the subject compounds are employed in combination
with suitable carriers, e.g., in solution, suspension, dust,
powder, ointment, emulsion, and the like forms, a high activity
over a very high range of dilution is observed. For example,
concentrations of the active ingredient ranging from 0.1 - 10
percent by weight, based on the weight of composition employed,
have been found effective in combatting fungi or bacteria. Of
course, higher concentrations may also be employed as warranted
by the particular situation.
The folloh7ing examples are intended to illustrate, but
not to limit, the scope of the present invention. Unless
other~7ise stated, all parts are by weight.
-22-
10S4079
Example
A stirred and cooled (0C) solution of 30 parts of 1-(4-
amino-2-methoxyphenyl)ethanone in 360 parts of a concentrated
hydrochloric acid solu~ion, 75 parts of water and 30 parts of
acetic acid is diazotated with a solution of 17.25 parts of
sodium nitrite in 200 parts of water. After stirring for 30
minutes at 0C, the whole is poured onto a solution of 30 parts
of copper(I) chloride in 240 parts of a concentrated hydro-
chloric acid solution while stirring. The mixture is heated
for 1 hour at 60C. After cooling to room temperature, the
product is extracted twice with 2,2'-oxybispropane. The com-
bined extracts are washed successively with water, a diluted
sodium hydroxide solution and again twice with water, dried,
filtered and evaporated, yielding 28 parts (76%) of 1-(4-chloro-
2-methoxyphenyl)ethanone;
; mp. 55C.
Example II
To a stirred mixture of 78.8 parts of 2-bromo-1-(4-
bromo-2-methylphenyl)-1-ethanone and 200 parts of butanol are
added 3 parts of 4-methylbenzenesulfonic acid and 225 parts
of benzene. Then there are added dropwise 33.5 parts of 1,2-
ethanediol. Upon completion, stirring is continued overnight
at reflux temperature with water-separator. The reaction mix-
ture is evaporated and the residue is dissolved in 2,2'-oxy-
bispropane. The solution is stirred with 15 parts of a concen-
trated sodium hydroxide solution. The layers are separated and
the aqueous phase is extracted with 2,2'-oxybispropane. The
combined organic layers are washed with water (till neutraliza-
tion), dried, filtered and evaporated. The solid residue is
crystallized from methanol, yielding 30.5 parts of 2-(bromomethyl)-
2-(4-bromo-2-methylphenyl)-1,3-dioxolane; mp. 86C.
-23-
1094079
Example III
Following the procedure of Example II and using therein
an equivalent amount of an appropriate l-aryl-2-bromo-1-ethanone
in place of the 2-bromo-1-(4-bromo-2-methylphenyl)-1-ethanone
used therein the following 2-aryl-2-bromomethyl-1,3-dioxolanes
are prepared:
4-[2-(bromomethyl)-1,3-dioxolan-2-yl]benzonitrile;
mp. 92.4C.; and
2-(bromomethyl)-2-(2-naphthalenyl)-1,3-dioxolane;
mp. 64C.
Example IV
57 Parts of 1-(5-chloro-2-thienyl)-1-ethanone are dis-
solved in 220 parts of 1,2-ethanediol at 50C. While stirring,
there are added dropwise, during a l-hour-period, 64 parts of
bromine without external heating. After stirring for 1 hour at
room temperature, 4 parts of 4-methylbenzenesulfonic acid and
360 parts of benzene are added. The whole is stirred and re-
fluxed overnight with water-separator. The reaction mixture
is evaporated and the residue is taken up in 2,2'-oxbispropane.
The resulting solution is washed successively once with a
diluted sodium hydroxide solution and three times with water,
dried, filtered and evaporated. The residue is distilled,
yielding 73.3 parts (64.5%) of 2-(bromo-methyl)-2-(5-chloro-
2-thienyl)-1,3-dioxolane;
bp. 125-127C at 0.1 mm. pressure.
ExamPle V
Following the procedure of Example IV and using therein
an equivalent amount of an appropriate l-aryl-l-ethanone in
place of the 1-(5-chlcro-2-thienyl)-1-ethanone used therein,
the following 2-aryl-2-(bro~omethyl)-1,3-dioxolanes are pre-
-24-
10~-~079
pared:
2-(bromomethyl)-2-(9H-fluoren-2-yl)-1,3-dioxolane; mp. 90C;
2-(bromomethyl)-2-(3-bromo-4-methylphenyl)-1,3-dioxolane;
bp. 126-130C. at 0.1 mm. pressure;
2-(bromomethyl)-2-(4-iodophenyl~-1,3-dioxolane; mp. 74C.;
2-(bromomethyl)-2-(4-chloro-2-methoxyphenyl)-1,3-dioxolane;
mp. 110C.; and
2-(bromomethyl)-2-(2,4-dibromophenyl)-1,3-dioxolane; mp. 96C.
Example VI
A. To a stirred solution of 2.3 parts of sodium in 120
parts of methanol are added 6.9 parts of lH-1,2,4-triazole in
150 parts of dimethylformamide. The methanol is removed at
normal pressure till the internal temperature of 130C. Then
25 parts of 2-(bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxo-
lane are added. The reaction mixture is stirred and refluxed
for 3 hours. It is allowed to cool to room temperature and
poured onto water. The precipitated product is filtered off
and crystallized from diisopropylether (activated charcoal),
yielding 12 parts of 1-~2-(2,4-dichlorophenyl)-1,3-dioxolan-
2-ylmethyl]-lH-1,2,4-triazole; mp. 109.9C.
B. 6 parts of 1-[2-(2,4-dichlorophenyl)-1,3-dioxolan-
2-ylmethyl]-lH-1,2,4-triazole are converted into the nitrate
salt in 2,2'-oxybispropane. After cooling, the salt is fil-
tered off and crystallized twice from 2-propanone, yielding
3 parts of 1-f2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]
-lH-1,2,4-triazole nitrate; mp. 172.7C.
C. 6 parts of 1-f2-(2,4-dichlorophenyl)-1,3-dioxolan-
2-ylmethyl3-lH-1,2,4-triazole are converted into the sulfate
salt in 2,2'-oxybispropane. The formed sulfate salt is fil-
-25-
1094079
tered off and crystallized from 2-propanol. The product is fil-
tered off and recrystallized from ethanol (activated charcoal),
yielding, after drying, 6 parts of 1-~2-(2,4-dichlorophenyl)-1,
3-dioxolan-2-ylmethyl]-lH-1,2,4-triazole sulfate; mp. 207.1C.
Example VII
To a stirred solution of 2.3 parts of sodium in 80 parts
of methanol are added 6.9 parts of lH-1,2,4-triazole and 2
parts of sodium iodide in 100 parts of N,N-dimethylformamide.
The methanol is removed at normal pressure till the internal
temperature of 130C. Then 34.4 parts of 2-(bromomethyl)-2-
(2,4-dichlorophenyl)-4-methyl-1,3-dioxolane are added and the
whole is stirred and refluxed for 3 hours. The reaction mix-
ture is poured onto water and the product is extracted twice
with diisopropylether. The extract is washed with water and
an excess of concentrated nitric acid solution is added. The
crude nitrate saIt is filtered off and crystallized from a
mixture of 2-propanol and diisopropylether, yielding 15 parts
of 1-[2-(2,4-dichlorophenyl)-4-methyl-1,3-dioxolan-2-ylmethyl]
-lH-1,2,4-triazole nitrate; mp. 137.8C.
Example VIII
To a stirred sodium methoxide solution prepared starting
from 2.8 parts of sodium in 48 parts of methanol, are added
8.3 parts of lH-1,2,4-triazole. After stirring for 30 minutes
at room temperature, 135 parts of N,N-dimethylformamide are add-
ed and the methanol is evaporated. Then there is added a mix-
ture of 24.3 parts of 2-(bromomethyl)-2-phenyl-1,3-dioxolane
and 3 parts of potassium iodide, and the whole is stirred and
refluxed for 3 hours. The reaction mixture is cooled to room
109407~
temperature and poured onto water. Upon scractching, the product
is precipitated. It is sucked off, washed with water, dried
and crystallized from a mixture of ethanol and 2,2'-oxybispro-
pane (1: 5 by volume), yielding 10.9 parts (43.7%) of 1-(2-
phenyl-1,3-dioxolan-2-ylmethyl)-lH-1,2,4-triazole; mp. 127.3C.
Example IX
Following the procedure of Example VIII and using therein
an equivalent amount of an appropriate 2-aryl-2-(bromomethyl)-1,
3-dioxolane in place of the 2-(bromomethyl)-2-phenyl-1,3-
dioxolane used therein, the following 1,2,4-triazoles are ob-
tained:
1-12-(4-nitrophenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-triazole;
mp. 160.1C;
1-12-(3-chlorophenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-triazole;
mp. 113.9C;
1-12-(4-bromophenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-triazole;
mp. 135.9C;
1-12- (3-methylphenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-triazole;
mp. 105.4C.;
1-12-(3-bromophenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-triazole;
n~p. 115.4C; and
1-[2-(3-nitrophenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-triazole;
mp. 154.1C.
Example X
To a stirred sodium m~3thoxide solution, prepared starting
from 1.6 parts of sodium in 48 parts of methanol, are added
4.9 parts of lH-1,2,4-triazole. After stirring for 1 hour at
room temperature, 135 parts of N,N-dimethylformamide are added.
The methanol is distilled off at normal pressure till internal
~ 7 ~
temperature of 130C. Then there are added successively 17.4
parts of 2-(bromomethyl)-2-(2,3,4-trichlorophenyl)-1,3-dioxolane
and 3 parts of potassium iodide. The whole is stirred and re-
fluxed overnight. After coolir.g to room temperature, the reac-
tion mixture is poured onto water. Upon scratching, the product
is precipitated, filtered off and washed with water. The pro-
- duct, dissolved in trichloromethane, is purified by column-
chromatography over silicagel, using a mixture of trichloro-
methane and 5% of methanol as eluent. The pure fractions are
collected and the eluent is evaporated. -The residue is
crystallized from a mixture of 2,2'-oxybispropane and methanol
(9 : 1 by volume), yielding 9.3 parts (55.5%) of 1-t2-(2,3,4-
trichlorophenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-triazole;
mp. 181.4C.
Example XI
Following the procedure of Example X and using equiva-
lent amounts of the appropriate starting materials, the follow-
ing 1,2,4-triazoles are prepared:
1-12-(9H-fluoren-2-yl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-
triazole; mp. 186.8C.;
1-[2-(5-chloro-2-thienyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-
triazole; mp. 117.4C.;
-28-29-
~0'~ ~079
1 -~2- (3 -bromo- 4-~ethylphen~ 13 -1, 3 -dioxolan-2 -yl-
rnethy_7-1H-1, 2, 4-triazole; mp. 120. 7C.;
1-~- (4-bron~o - 2 -methylphenyl) - 1, 3 -dioxolan- 2 -yl-
methyl7-lH-1,2,4-triazole; rnp. 148.1C; and
1-~2- (4- chloro-2 -methylphenyl)- 1, 3 -dioxolan-2-yl-
methyl7-lH-1, 2, 4-triazole; mp. 147. 9~C.
':
,
Ex ample XII
:'
~,
,.
To a stirred sodium methoxide solution, prepared starting
from 2. 8 parts of sodium in 56 parts of methanol, is added a mixture
of 8. 3 parts of 1H-1, 2, 4-triazole and 135 parts of N,N-dimethyl-
formamide. The methanol is removed at normal pressure till an
internal temperature of 130C. is reached. Then there is added a
mixture of 27. 8 parts of 2 (~romomethyl)-2-(2-chlorophenyl)-1, 3-
dioxolane and 3 parts of potassium iodide. The whole is stirred and
refluxed for 6 hours. The reaction mixt-lre is allowed to cool to
room temperature, poured onto water and the product is extracted
three times with 1, l'-oxybisethane. The combined extracts are
washed twice with water, dried, filtered and evaporated. The
residue is ~onverted intQ the ethanedioate salt in 4-Inethyl-2-
pentanone. The salt is filtered off and crystalli~ed from 4-methyl-
2-per.tanone, yielding 16 part~ of 1-[2~ chlorophenyl~-l,3-dioxolan-
2-ylmethy'7--lH-1, ~,4-tri~ole ethanedioate; mp. i~6. ~C. .
~'
.
.
t
10'? ~C)7~
Example XIII
Following the procedure of Example XII and
u6ing equiva!ent amounts of the appr~priatP starting
materialst the follo~Ying 1, 2, 4-triazole ethanedioate
- salt~ are prepared:
r
~JJ
X
IJ
Ar Acid salt meltin~ point
2-Br-C6H4 (cOOH)2 172. 1 C.
3 6 4 (COOH)2 155. 6C.
3 6 4 (~;OOH)2 ~77. 1 C.
4-F-C6H4 (COOH)2 185. 5C.
4- CH3 - C6H4 (COOH)z 1 51. 2 C.
4-Cl-C6H4 (C~2 . H20 169. 1 C.
3 6 4 (COC~H)2 187. 1 C.
2 -naphthalenyl (COOH)2 17 5 C.
2, 5-(C1)2-C6H3 (COOH)2 ,73. 7C.
4- C~- C6H4 ~COOH)z 186. 3 C.
3~4-(C1)2-C6H3 ~COOHJ2 182. 2C.
2-thienyl (C00~1~2 144. 5~C.
2t 4- (BrJ2 ~ C6~I3(COOHJ2 190. 3 C.
--31-
10~4079
Examp`le XIV
To a stirred sodium methoxide solution, prepared starting
from 2.3 parts of sodium in 48 parts of methanol, are added 6.9
parts of lH-1,2,4-triazole. After stirring for 30 minutes at
room temperature, 135 parts of N,N-dimethylformamide are added.
The methanol is distilled off at normal pressure till internal
temperature of 130C. Then there are added successively 3 parts
of potassium iodide and 16.4 parts of 2-(bromomethyl)-2-(o-
methoxyphenyl)-1,3-dioxolane. The whole is stirred and refluxed
for 18 hours. After cooling to room temperature, the reaction
mixture is poured onto water and the resulting solution is
extracted three times with trichloromethane. The combined ex-
tracts are washed four times with water, dried, filtered and
evaporated. The residue is purified by column-chromatography
over silicagel, using a mixture of trichloromethane and 5% of
methanol as eluent. The pure fractions are collected and the
eluent is evaporated. The residue i9 converted into the
ethanedioate salt in 4-methyl-2-pentanone. The salt is fil-
tered off and crystallized from a mixture of 2-propanone and
2,2'-oxybispropane (2 : 1 by volume), yielding 5.5 parts (26%)
of l-[2-(2-methoxyphenyl)-1,3-dioxolan-2-ylmethyl] -lH-1,2,4-
triazole ethanedioate; mp. 166.4C.
Example XV
Following the procedure of Example XIV and using equiva-
lent amounts of the appropriate starting materials, the follow-
ing l,2,4-triazole ethanedioate salts are prepared:
1-[2-(4-iodophenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-triazole
ethanedioate; mp. 169.8C.;
1-[2-(3,5-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-
triazole ethanedioate; mp. 204.4C.;
1-[2-~2,3-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-
-32-
l~9i~0 79
triazole ethanedioate; mp. 188.4C.;
1-[2-(4-chloro-2-methoxyphenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,
4-triazole ethanedioate; mp. 173.2C.;
1-12-(2,4,5-trichlorophenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-
triazole ethanedioate; mp. 178.4C.; and
1-[2-(2-chloro-4-methoxyphenyl)-1,3-dioxolan-2-ylmethyl]-lH-l,
2,4-triazole ethanedioate; mp. 188.2C.
Example XVI
To a stirred mixture of 9.5 parts of lH-1,2,4-triazole
and 225 parts of N,N-dimethylformamide are added portionwise
4.2 parts of a sodium hydride dispersion 78%. After stirring
till foaming is ceased, there are added 16 parts of 2-(~romo-
methyl)-2-(2,4-dichlorophenyl)-4-propyl-1,3-dioxolane and
stirring is continued for 5 hours at reflux temperature. The
reaction mixture is cooled and poured onto water. The product
is extracted three times with 2,2'-ox~bispropane. The combined
extracts are washed with water, dried, filtered and evaporated.
The residue is purified by column-chromatography over silicagel
using a mixture of trichloromethane and 2% of methanol as
eluent. The first fraction is collected and the eluent is
evaporated. The residue is converted into the nitrate salt
in 2,2'-oxybispropane. The salt is filtered off and crystal-
lized from a mixture of 2-propanone and petroleumether, yield-
ing 8.2 parts ~45%) of 1-~2-(2,4-dichlorophenyl)-4-propyl-1,3-
dioxolan-2-ylmethyl]-lH-1,2,4-triazole nitrate; mp. 132.6C.
Example XVII
To a stirred sodium methoxide solution, prepared start-
ing from 3.8 parts of sodium in 40 parts of methanol, are
added 11.5 parts of lH-1,2,4-triazole and 225 parts of N,N-
dimethylformamide. The methanol is distilled off till internal
-33-
10~079
temperature of 150C. After the addition of 19 parts of 2-
(bromomethyl)-2-(2,4-dichlorophenyl)-4-ethyl-1,3-dioxolane,
the whole is stirred and refluxed for 4 hours. The reaction
mixture is cooled and poured onto water. The product is ex-
tracted three times with 2,2'-oxybispropane. The combined
extracts are washed with water, dried, filtered and evaporated.
The residue is purified by column-chromatography over silica
gel using a mixture of trichloromethane and 2% of methanol as
eluent. The first fraction is collected and the eluent is
evaporated. The residue is converted into the nitrate salt in
2,2'-oxybispropane. The salt is filtered off and recrystallized
from a mixture of 4-methyl-2-pentanone and 2,2'-oxybispropane,
yielding 10.5 parts (49~) of 1-[2-(2,4-dichlorophenyl)-4-ethyl
-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-triazole nitrate; mp.
119.8C.
Example XVIII
Following the procedure of Example XVII and using equiva-
lent amounts of the appropriate starting materials, the
following 1,2,4-triazole acid addition salts are prepared:
1-[4-butyl-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]lH-l,
2,4-triazole sesquiethanedioate; mp. 111.6C.;
1-~2-(2,4-dichlorophenyl)-4-pentyl-1,3-dioxolan-2-ylmethyl]-lH
-1,2,4-triazole nitrate; mp. 130.3C.;
1-[2-(2,4-dichlorophenyl)-4-hexyl-1,3-dioxolan-2-ylmethyl]-lH
-1,2,4-triazole nitrate; mp. 106.2C.;
1-[2-(2,4-dichlorophenyl)-4-heptyl-1,3-dioxolan-2-ylmethyl]-lH
-1,2,4-triazole nitrate; mp. 96.8C; and
1-[2-(2,4-dichlorophenyl)-4-octyl-1,3-dioxolan-2-ylmethyl~-lH
-1,2,4-triazole nitrate; mp. 110.6C.
-34-
10S~079
EXample XIX
By repeating the procedure of Example VI-A, except that
the 2-~bromomethyl)-2-(2,4-dichlorophenyl)-1,3-dioxolane used
therein is replaced by an equivalent amount of an appropriate
2-(bromomethyl)-2-aryl-1,3-dioxolane, the following compounds
of formula (I) are obtained respectively:
1-12-(2,4,6-trichlorophenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,
4-triazole;
1-[2-(2,6-dichlorophenyl)-1,3-dioxolan-2-ylmethyl~-lH-1,2,4-
triazole;
1-[2-(2-chloro-4-methylphenyl)-1,3-dioxolan-2-ylmethyl]-lH,1,2,
4-triazole.
Example XX
The procedure of Example VII may be used to prepare
compounds of formula (I) wherein Z is -CH2-CH(CH3)- or
-CH(CH3)-CH(CH3)-. Accordingly, by substituting therein an
equivalent amount of an appropriate 2-aryl-2-(bromomethyl)-4-
methyl-1,3-dioxolane or 2-aryl-2-(bromomethyl)-4,5-dimethyl-
1,3-dioxolane, the following compounds are obtained respective-
ly in the form of a nitrate salt:
1-(4-methyl-2-phenyl-1,3-dioxolan-2-ylmethyl)-lH-1,2,4-triazole;
1-~2-(4-chlorophenyl)-4-methyl-1,3-dioxolan-2-ylmethyl]-lH-1,2,
4-triazole;
1-~2-(2-chlorophenyl)-4-methyl-1,3-dioxolan-2-ylmethyl]-lH-l,
2,4-triazole;
1-[4-methyl-2-(4-methylphenyl)-1,3-dioxolan-2-ylmethyl]-lH-l,
2,4-triazole;
1-[2-(4-methoxyphenyl)-4-methyl-1,3-dioxolan-2-ylmethyl]-lH
1,2,4-triazole;
-35-
1094079
1-[4,5-dimethyl-2-(2,4-dichlorophenyl)-1,3-dioxolan-2-ylmethyl]
-lH-1,2,4-triazole;
1-(4,5-dimethyl-2-phenyl-1,3-dioxolan-2-ylmethyl)-lH-1,2,4-
triazole; and
1-~2-(4-chlorophenyl)-4,5-dimethyl-1,3-dioxolan-2-ylmethyl]-
lH-1,2,4-triazole.
Exam~le XXI
The procedure set forth in Example VI-A may be utilized
to prepare those compounds of formula (I) wherein Z is
-CH2-CH2-CH2-. Accordingly, by substituting therein an
equivalent quantity of an appropriate 2-ary1-2-(bromomethyl)
-1,3-dioxane as starting material, the following are obtained
respectively:
1-(2-phenyl-1,3-dioxan-2-ylmethyl)-lH-1,2,4-triazole;
1-12-(2,4-dichlorophenyl)-1,3-dioxan-2-ylmethyl]-lH-1,2,4-
triazole;
1-~2-(4-chlorophenyl)-1,3-dioxan-2-ylmethyl]-lH-1,2,4-triazole;
1-[2-(4-methylphenyl)-1,3-dioxan-2-ylmethyl]-lH-1,2,4-triazole;
1-[2-(4-methoxyphenyl)-1,3-dioxan-2-ylmethyl]-lH-1,2,4-triazole;
1-~2-(2-thienyl)-1,3-dioxan-2-ylmethyl]-lH-1,2,4-triazole; and
1-[2-(2-naphthyl)-1,3-dioxan-2-ylmethyl]-lH-1,2,4-triazole.
Example XXII
The compositions according to this invention are em-
ployed in those forms which are customarily used for fungus or
bacteria control, for example, as suspensions, dusting powders,
solutions, ointments and the like. The following will further
illustrate the in~ention, the parts being parts by weight
unless otherwise specified:
-36-
~ 4079
(1) SUSPENSION:
1 kg. ... 1-[2-(2,4-dichlorophenyl)-1,3-dioxolan-
2-ylmethyl]-lH-1,2,4-triazole
2 1. ... technical xylene
350 ml. ... Surfactant
Water ... dilute to desired concentration to ac-
tive ingredient
The 1-[2-(2,4-dichlorophenyl~-1,3-dioxolan-2-ylmethyl]
-lH-1,2,4-triazole forms a stable aqueous suspension when dis-
solved in the xylene and emulsified by means of the surface
active agent.
(2) DUSTING POWDER: 20 parts of 1-[2-(2,4-dichloro-
phenyl)-1,3-dioxolan-2-ylmethyl]-lH-1,2,4-triazole are ground
with 360 parts of talcum in a ball mill, then 8 parts of olein
are added and grinding is continued, and finally the mixture
is mixed with 4 parts of slaked lime. The powder which is
formed can be sprayed satisfactorily and has good adhesive
power. It can be used for dusting or for plant protection pur-
poses.
(3) SOLUTION: 5 parts of 1-[2-(2,4-dichlorophenyl)-1,3-
dioxolan-2-ylmethyl]-lH-1,2,4-triazole are dissolved in 95 p.rts
of alkylated naphthalene and used as a spray for the treatment
of fungus-infected subjects or on walls, floors, or other ob-
jects to prevent infection by fungi.
(4) OINTMENT: 10 parts of 1-[2-~2,4-dichlorophenyl)-
1,3-dioxolan-2-ylmethyl]-lH-1,2,4-triazole are dissolved in a
warm, liquefied mixture of 400 parts of polyethylene glycol
400 and 590 parts of polyethylene glycol 1500. The solution
is stirred during cooling, and used as an ointment for treat-
ment against fungi and bacteria.
