Note: Descriptions are shown in the official language in which they were submitted.
I 1 71~
Case 136-6878
The present invention relates to a-aryl-lH-1,2,4-
triazole-l-ethanols, more particularly a-alkyl-~-phenyl-
lH-1,2,4-triazole-l-ethanols, their use as fungicides
and agricultural compositions for facilitating such use.
More specifically, the present invention provides
compounds of formula I,
R~ OH ~=~N
C - CH -N J
R~
wherein R is alkyl of l to 12 carbon atoms, cyclo-
alkyl of 3 to 8 carbon atoms or cyclo-
alkylalkyl of 4 to ll carbon atoms in
which the cycloalkyl portion is of 3 to
8 earbon atoms and the alkyl portion of
1 to 3 earbon atoms, said eycloalkyl and
eyeloalkylalkyl aroups being optionally
substituted by one or two alkyl group~
of 1 to 3 carbon atoms,
R is hydrogen, halogen having an atomic
number of from 9 to 35, alkyl of l to 4
earbon atoms, mono-, di- or tri-halo-
alkyl of l to 4 earbon atoms in whieh
the halo is independent].y an halogen
ha~ing an atomie number of from 9 to 35,
alkoxy of l to 4 earbon atoms, alkylthio
~ ~.
' 17186~
- 2 - 13~-687
of 1 to 4 carbon atoms, or nitro, and
R' is hydrogen, halogen having an atomic
number of from 9 to 53, alkyl of 1 to 4
carbon atoms, mono-, di- or tri-halo-
alkyl of 1 to 4 carbon atoms in ~hich
the halo is inde~endently an halogen
having an atomic number of from 9 to 35,
alkoxy of 1 to 4 carbon atoms, mono-,
di or tri-haloalkoxy of 1 to 4 carbon
atoms in which the halo i5 independently
an halogen having an atomic number of
from 9 to 35, alkylthio of 1 to 4 carbon
atoms, nitro, -CN, -COOR",
Y
Y or
yO
- Z~
R" is hydroyen, alkyl of 1 to 4 carbon atoms,
R"' is hydrogen, an halogen having an atomic
number of from 9 to 17 or alkyl of 1 or
2 carbon atoms,
Z is oxygen or sulfur, or
R and R' together represent alkylenedloxy o 1 or
2 carbon atoms substituted onto a.djacent
carbon atoms of the phenyl ~ing A, and
~ 17186B
- 3 - 136-6878
Y and Y are independently hydrogen, halo~en
having an atomic number of from 9 to 35,
alkyl of 1 to 4 carbon atoms or a].koxy of
1 to 4 carbon atoms.
Halogen atoms having an atom.ic number of from 9 to 53
are fluoro, chloro, bromo and iodo, such having an atomic
number of from 9 to 35 are fluoro, chloro, bromo and those
having an atomic number of from 9 to 17 are fluoro and
chloro.
When any R or R' is or includes mono-, di- or tri-
haloalkyl this is e.g. CF3
The invention also provide~s processes for the
production of compounds of formula I comprising
a) reacting a compound of the formula II:
H2C~
R ~ / O II
R' ~ CRo
R"'
wherein R, R, R' and R"' are as above defined, with
a compound of forrnula III
X-N III
~-
wherein X is an alkali metal in an inert organic
solvent,
b) obtaini.ng a compound of forrnula Ia,
' ~71866
- 4 - 136-6878
R ~ , 2 ~N ~ Ia
HOOC R
wherein R and R are as defined above
by oxidation of the CH3 group of a compound of formula Ib,
R ~ C - CH2 - N ~ Ib
wherein R and R are as defined above, or
c) obtaining a compound of formula Ic,
AlkOOC ~ C - CH2 - N ~ Ic
where1.n R and R are as defined above and
1~11. i~ Cl_ 4alkyl,
by esterification of a compound of formula Ia ~1ith an
alcohol. of formula IV
Alk-OH IV
wherein Alk. is as defined above, or a reactive
nctional derivative the~eof.
The process a) may be carried out at temperatures
typically fxor.l 0C to 1.80, preferably ~0C to 120C, in
an inert organic solvent of conventional type, e.g. an
amide of an oxganic carboxylic acid such as dimethyl-
forrnamide. ~s is conventional, the compound of the
forrnula III is preferably prGvided by reacting tr.ia~ole
with a strong base such as an alkaii metal hydride e.g.
sodil1m hydride, in an inert organic solvent which is
- -`` ! 171866
conveniently the same solvent which is to be used in
process a).
The oxidation according to process b) may be carried
out with the aid of oxidizing agent capable of oxidizing
an CH3-group to a COOH group. Suitable oxidizing agents
are potassium permanganate, manganese dioxide and the like,
preferably potassium permanganate. The reaction is conven-
iently carried out in aqueous solution. A suitable
reaction temperature for process b) is from 20 to 150C,
preferably from 60 to 120C.
The compounds of formula Ia are depending on the
reaction conditions and the recovery steps obtained in
free form or in salt form (H of- COOH substituted by a
cation). Free forms of compounds of formula Ia may be
converted into salt forms in conventional manner and vice
versa. The cation of the salt form of compounds of
formula Ia is preferably an agriculturally acceptable
cation such as Na , K and NH4
The process c) may be carried out in accordance with
known esterification procedures for compounds containing a
potentially reactive hydroxyl group. The esterification
with an alcohol of formula IV is conveniently carried out
at a reaction temperature of from 30C to 80C, advant-
ageously under anhydrous conditions and in the presence of
an acid, such as hydrogen chloride. Suitable solvents for
this reaction are inert organic solvents or an excess of
the alcohol of formula IV.
~ 171S~66
- 5a -
Suitable reactive functional derivatives of an alcohol
of formula IV are the corresponding diazoalkane, e.g. a
diazoalkane of 1 to 3 carbon atoms, or an alkylhalide,
particularly a chloride, bromide or iodide. The reaction
with a diazoalkane is conveniently carried out under anhy-
drous conditions in an inert organic solvent. A suitable
reaction temperature is then -20C to +40C, more usually
-5C to +20C. For the reaction with an alkylhalide the
compounds of formula Ia are preferably in salt form, e.g.
the alkali metal and silver salt form. Such reaction is
conveniently carried out in an inert organic solvent at
temperatures of from 0C to 100C, more usually 40C to
90C .
The reaction product of processes a), b) and c) may
be recovered from the reaction mixture in which it is
formed by working up by established procedures.
The compounds of formula I wherein R' is other than
COOH may be prepared and used in the form of acid addition
- salt forms. The compounds of formula I are ethanol deriva-
tives and can therefore exist in free form and in alternate
forms such as an ethanolate salt form, e.g. a sodium
ethanolate form, and in metal complex form, e.g. of metals
from the groups Ib, IIa, IIb, VIb, VIIb and VIII of the
periodic table, such as copper and zinc, and with anions
such as chloride, sulphate, nitrate, carbonate, acetate,
citrate, dimethyldithiocarbamate and the like.
J 171~66
Any salt form of compounds of formula I is preferably
in the form of an agriculturally acceptable salt form.
The acid addition salt forms, the ethanolate salt form
and the metal complex form can be prepared from the corres-
ponding free form in conventional manner and vice versa.
The compounds of formula II may be prepared byreacting a compound of the formula V
R
~ R"' V
R - C = O
wherein R, R, R' and R"' are as above defined, with
10 the reaction productof a strong base andtrimeJchy]sulfonium
iodide which provides a rea~ent which may be repre~ented
by the formula VI
CH3
CH 1~ CH e VI
which process is carrled out in an inert organic
15 solvent. This process is a known type reaction for the
- preparation of epoxy derivatives from ketones.
Many of the compounds of the formula V are kno~7n
and those whlch are not known E~ se may be prepa~red
f~om known ~aterials b~ procedures analogous to those
20 known for preparation of the known compounds. Ilany of the
compounds II are also known.
~ 171866
- 7 - 136-6878
The compounds of the formula I are useful as fungi-
cides in combatting phytophathogenic fungi including
particularly powdery mildews and rust fun~i, as indicated
by standard in vivo and in vitro tests of the type
hereinafter illustrated. ~or such use the compounds of
.he formula I may be applied to plants seed or ~oil in
a manner conventional in the use of fungicidal agents.
As will be appreciated, the amount of the compound of the
formula I to be applied will vary depending upon Xnown
factors such as the particular compound employed,
whether the treatment is prophylactic or therapeutic
whether the compound is applied as a foliar spray, a
~oil treatment or a seed dressing, the species of fungus
under treatment and the time of application. Ilowever, in
general, satisfactory re~sults are obtained when the
compound is applied to a crop locus, either on crops or
to 5011, at a rate of from about O.OOS to 2, preferably
about 0.01 to 1 kg (active ingredient)/hectare. The
treatment may be repeated as required, e.g. at 8 to 30
day intervals. When employed as a seed dressing, satis-
factory results are obtained when the compound is
employed at a rate of irom about O.OS to O.S, preferab].y
about 0.1 to 0.~ g/]cg seed.
The term 'soil' a~ used herein is intended to
embrace any conventional growing medium whether natural
or artiflcial.
.
1 ~71866
- 8 - 136-6878
The invention also provides, as an additional
feature, fungicidal compositions, comprising, as fungi-
cide, a compound of for~.ula I in free fo~m or in
agriculturally acceptable salt form and an inert
fungicide carrier or diluent. In general, such composi-
tions contain from about O.OC05 to 9o, preferably from
about 0.1 to 50% by wei~ht of active agent. They may
be in concentrate form, for dilution down prior to appli-
cation, or in dilute, ready ~o apply, form. As examples
of particular form~ may be given wettable powder,
emulsion concentrate, dusting, spraying, granulate and
delayed release forms~ incorporating conventional
carriers and sucn other diluents and/or adjuvants
acceptable in the agricultural art. Application ~orms
of those compositions generally contain between about
0.0005 and 10~ by .~eight of a compound of formula I as
active agent. Typical spray suspensions may contain, for
example, from 0.0005% to 0.05%, preferably 0.001~ to 0.02
by ~Jeight of active ingredient. Concentrate forms of
composition~ for fungicide use generally contain bet~een
about 2 and 90%, preferably between about 5 and 70%, by
weight of a compound of formula I as active agent.
Emulsion concentrate forms aenerally contain from about
10 to 70%, preferably about 20 to 60% by welyht of active
ingredient. Solid, particulate composltions are preferred.
The compositions particularly adapted for spraying
preferably include a surfactant swch as a liquid ooly-
- ` ' 171866
- 9 - 136-~878
glycol ether, a fatty alkyl sulphate or a lignin sulpho-
nate.
In addition to conventional caxrier and surface-
active materials, formulations of the compound I of the
invention may also contain further additives with special
purposes e.g. stabilizers, deactivators (for solid f~rmu-
lations on carriers with an active surface), agents for
improving the adhesion to plants, corrosion inhibi~ors,
anti-foaming agents and colorants.
Moreover, further fungicides, bactericides or other
beneficially-acting materials, such as insecticides,
may be present in the formulations and are contemlated
as further er~odiments of this invention.
Exarnples of the production of fungicide formulations
are as follows:
a) Wettable_e_wder formulation
50 part~ of a compound of formula I, e.g~ ~-t-butyl-
a-(p-methylphenyl)-1~1-1,2,4-triazole-1-(?,thanol are ground
with 2 parts of lauryl sulphate, 3 parts sodium lignln
sulphonate and 45 parts of finely divided kaolinite until
the mean particle size is below 5 microns. The resulting
spray liquor may be applied bv foliar spray as ~Jell as hy
root drench application.
b) Granulat,e formulat _n
25, Onto 94.5 parts by wei~ht of quartz sanci in a tumhler
mixer i9 sprayed 0.5 parts by ~leiaht of a binder (non-
ionic tensi.de) and the whol,e thoroughly mi~:ed. 5 Parts
~ 171866
- 10 - ~36-6878
by weight of a compound of formula I, e.g. powdered
~-t butyl-a-(p-methylphenyl)-lH-1,2,4-triazole-1-ethanol
are then added and thorough mixing con~inued to obtain a
granulate formulation with a particle size in the range
of from 0.3 to 0.7 mm. The granulate may be applied
by incorporation into the soil adjacent the p]ants to be
treated.
c) Emulsion Concentrate
. _ .
25 Parts by weiaht of a compound of formula I, e.g.
a-t~-butyl-a-(p~methylphenyl)-1~-1,2,4-triazole-1 ethanol
are mixed with 30 parts by weight of iso-octyl phenyl
octaglycol ether and 45 parts by weight of a petroleum
fraction with a boiling ranse of 210-280C (D2o:0.92).
The concentrate is diluted with water to the desired
concentration.
d) Seed dres~
45 Parts of a compound of a compound of formula I, e.g.
~-t-butyl-a-(p-methylphenyl)-lH-1,2,4-triazole~l-ethanol
are mixed with 1.5 parts of diamyl phenoldecaglycolether
20 ethylene oxide adduct, 2 parts of spindle oil, 51 parts
of fine talcum and 0.5 parts of colorant rhodamin B. The
mixture is ground in a contraplex mill at 10,000 rpm until
an average particle of less than 20 microns is obtained.
The resulting dry seed dressing powder has good adherance
25 and may be applied to seeds, e.g. by mixing for 2 to 5
minutes in a slowly turning vesse].
'
! 1718f66
~ ,6-6878
Fungi a~ainst which the compounds of the formula I
are indicated to be particularly of interest include by
way of illustration i:he following:
A) _ S 1 m~es, comprisi~g
S A.l) those of the Order Uredinales such as those of the
genus Uromyces in plants such as beans, e.g. Uromyces
aE~endicu1atus, and orna~.entals, e.g. UromYces dianthi,
those of the genws Hemileia in plants such as coffee,
-
e.~. Hemileia vastatrix, those of the genus Puccinia
in plants such as cereals (e.g. whea~, oats, barley) e.g.
Puccinia graminis, Puccinia recondita and Puccinia
striiformis, or ornamentals, e.g. _ccinia ~araonii-
zonalis and Pucc. antirrhin , those of the genus
Phakopsora in plants such as soya, e.g. Phako~so~a
~ y~ , those of the genus ~ in plants such
flax, e.g. ~ llni, and those of the genus
ranz~chelia, e.g. ~ranzschella pruni in plums;
A.2) those o the Order IJstilaginales such as those of
the ~enus Ust~ in plants such as barley, wheat, corn
and sugarcane, e.g. U. maydis on corn and U. nuda on
barley, and
P..3~ those of the ~enus Stereum in pip and stone fruit
~rees, e.g. Stereum ~ur~ureum in apple and prune.
B) Ascom~_etes, comprislng
B,l) those of the Order Erysiphales such as thosn of
the genus Ery_~he in plants such as cucumber, barley,
~heat and sugarbeet, e.g. ~r~s~he ~r ~inls f.~. t~itici
! 17t866
- 12 -
on wheat and Erysiphe cichoraceareum on cucumbers; those
of the genus Spohaerotheca on cucumbers and roses, e.g.
Spohaerotheca pannosa on roses; those of the genus
Podosphaera in apples, pears and prunes, e.g. Podosphaera
leucotricha on apples; those of the genus Uncinula on
_. .
plants such as grapes, e.g. Uncinula necator on grapevines;
those of the "genus" Oidium on a wide variety of plants;
and those of the genus Leveillula in plants such as cotton
and other Malvaceae, e.g. Leveillula taurica on cotton.
C) Oomycetes, comprising
C.1) those of the genus Phytophthora spp., e.g. Ph.
cactorum, Ph. parasitica and Ph. cinamomi on susceptible
plants; and
C.2) those of the genus Aphanomyces in plants such as
pea and sugar beet, e.g. Aphanomyces euteiches in sugar
beet, and
D) Deuteromycetes, comprising
D.l) those of the genus Helminthosporium in plants such
as barley and corn, e.g. Helm. Sativum;
D.2) those of the genus Septoria in plants such as wheat,
tomato and celery, e.g. Sept. tritici in wheat, tomato and
celery, e.g. Sept. tritici in wheat;
D.3) those of the genus Rhizoctonia in plants such as
cotton and potato, e.g. Rhiz. solani in cotton;
D.4) those of the genus Fusarium spp, e.g. F.oxysporum
f. sp. lycopersici in tomato, F. oxysporum f. sp. vasin-
fectum in cotton, F. oxysporum f. sp. cubense in banana,
,, -.~
!~,
-
! 171~66
- 13 - 13~-6~78
F. solani in vegetables, F. culmorum in cereals and
F. ~raminearum in cereals;
D.5) those of the genus Thiela~iiopsis in plants such as
cotton, tobacco etc., e.g. Th'ielaviopsis'basicola in
co~ton;
D.6) those of the genus Phoma in plants such as sugar
beet, rape etc., e.g. Phoma betae in suyar beet;
D.7~ those of the genus P icularia spp,, e.g. P.ory~ae
- on rice; and
D.8) those of the genus Colletotrichum sp~., e.g.
C. lindemuthianum in beans.
The followin~ conventional tests are i].lustrative of
the manner by which the fungicidal activity of the
',' compounds of the formula I may be inaicated.
~, 15 'rest Method A: In vivo employing bean rust (Uromyces
appendiculatus). Phaseolus vulgaris (pole bcan plant) is
cultivated in a mixture of peat and sand in plastic pots
~ of 6 cm diameter for 9 days. The plants are sprayed with
" a spray liquor containing 0.0008 to 0.05~ (e.g. at
20 0.0008%, O.OG3~, 0.012~ and 0.05%) active inyredient.
Treatment comprises foliar spraying to near run-of f or
soil drenching (28 ml of spray liquor per pot). ~fter
, dryi.ng, the plants are inoculated "ith a spore suspension
;, s~ray (S00,~00 to 700,000 spores/ml) and in.,ubated for
7 days in an incubatiQn chamber at 100~ relative humidity
and 21. The sfficacy of the active agent treatment is
-
- g ~71866
- 14 - 136-6878
determined by comparing the number OL pustulesjleaf with
that on untreated, similarly inoculated check plants.
The compounds of formula I, particularly ~he compour~ds of
the Examples hereinafter e.g. the co~ ounds of the E~,les
5 1, lA, lB, lC, 2A, 2B, 2D, 2F, 2G, 2I~, 2L, 2N, ~, 2Z-l, 2'Z~3~ 2~-4,
2Z-7, 2Z-8, 2Z-9, 2Z-11, 2Z-13, 2Z-1~, 2Z-15, 2Z-24~ 2Z-27~ 2Z-28
2Z-32, 2Z-33~ 2Z-41t,o 2Z-44 and 3 hereinaf~er used in
the wettable powder formulation given above provide a
significant degree of funyicidal activity in the above
lOtest, botn by contact as well as root-systemic action.
Anzlogous tests are run on the following crc)p/fungi
with similar results.
Coffee : cofee leaf rust (Hemileia vas~atrix)
Wheat : black stem rust (Puccinja graminis)
15Wheat : bro~n leaf rust (Puccin1a recondita)
~eat : yellow ~r striPe rust (Puccinia strii-
forrni,s)
Flax : fl.ax rust (Melarns~ora Li.nl)
Pelargonlum : Pelargonium rust (Puccinia pelaryonii.-
20 ' zonali )
Snapdragon : Sn~pdragon rust (Puc~cinia antirrhin~.).
" Test ethocl B: In vivr) employing cucumber po~ldery
mi.ldew ~y~Ehe cichor cearum). Cucumis sati,vus (cucumber)
. 1~ cultlvated ln a mi,Y.ture of peat and sand in plastic
', 25pots of 6 cm diarneter for 7 days. The plants are spra~ed
with a spray l.iquor contai.nlng 0.0008 to 0.05~ (e.g. at
,0.0008%, 0.(~03~, 0.012~ arld 0.05~,) acti.ve ingre~diellt.
,,
1 ~71 ~fi~
- 15 - 136-6878
Treatment cornprises foliar spraying ~o near run-off or
soil drenching (28 ml of spray liquor per pot). After
drying, the plants are inoculated by dusting them with
freshly collected conidia and are then incubated for
7 days in an incubation chamber at 60-80% relative
humidity and 25-30C. The efficacy of the active ingre-
dient is determined by cornparing the degree of fungal
attack with that on untreated, similarly inoculated check
plants. The compounds of formula I particularly ~he
10 compounds of the examples hereinafter, e.g. the cornpounds
of the Examples 1, 2A, 2B, 2C, 2D, 2F, 2G, 2H 2L 2N 2P,
2Q, 2R, 2S 2T, 2U, 2V, 2Z-1 2Z-3 2Z-4, 2Z-6 to 2z-~,-2z-11
2Z-13 to 2Z~15, 2Z-24, 2Z-26, 2Z-27, 2Z-2~, 2Z-35,
2Z-~0 to 2Z-~7, lA, lB, IC and Example 3 hereinafter
15 us~d in the wettable powder formulation given above
~r, provide a significant degree of fungicidal activity,
both by contact as well as root-systemic action.
T~sts analogous to Test ~iethod B are made with
similar results on the follo-"ing crop/fun~i:
20 Wheat : wheat powdery mildew (Erys. ~m. f.s tritici)
Barley : barley powdery mildew (Erys. gram. f.s hordei)
Apple : apple powdery mildew (Podos _eu~otr1cha)
Grape : grapevi.ne powdery mildew ( ncinula r.ecator)
: Test Method B, above, as regards cucumber po-,7dery
25 mildew and the preferred compound of Exarnple 1, herein-
after is repeated (both foliar spray and soil drench) but
at t}le low~r concentrations 0c 0.0002% and 0.00005~ with
- 16 - 136-6878
the result that 100% control of the fungi is still
obtained, thereby still further indicating the remark-
able potency provided by the invention. At concentrations
of 0.000012% and 0.000003% in the same test a control of
70% and 50%, respectively, is obtained in spray applica-
tion and a control of 90% and 70%, respectively in the
soil drench application. In repeating Test Method B, above,
against barley powdery mildew at the 0.0002% and 0.00005%
concentrations a control of 70% and 55%, respectively, is
obtained on spray application and a control of 80% and
70%, respectively, is obtained in soil drench application.
Against wheat powdery mildew in the Test Method B at
the 0.0002% and 0.00005% concentrations a control of
80% and 60%, respectively, is obtained on spray applica-
tion and a control 90% and 70%, respectively, in the soil
drench application.
Test Method C; In vitro test employing Ustilago
maydis (corn smut). Different concentrations of the active
ingredient are incorporated in malt agar plates to give
concentrations of 0.8 to 200 ppm a.i. (e.g. at 0.8, 3.2,
12.5, 50 and 200 ppm). The plates are then inoculated by
spraying a spore suspension of U. maydis onto them or
placing an agar plug containing the fungis in the centre
of the plate. The plates are incubated at room temperature
for 2-5 days. The efficacy of the active agent treatment
is determined by comparing the growth of the fungus with
that in untreated, similarly inoculated plates. The
'--
~ ~71866
- 17 - 136-6878
compounds of formula I provide moderate to good cor.trol
in test Method C. The compounds of Exarnple 1, 2A and
2Z-l hereinafter provide for example good control at
both the lo~7er and higher concentrations in r~est Method
5 C. In an analogous test on Fusarium oxysporum f.sp. the
t~ compounds of formula I, e.g. the compounds of Example 2A,
2~, 2D, 2P, 2R, 2S, 2Z, 2Z-32, 2Z-34 and 2Z-46 herein-
after provide rnoderate to good control~
Fungi of the aforementioned ~enera cause considerable
0damage ln agriculture and are difficult to prevent or
~ control. In addition to combatting such fungi, the
;, compounds of the formula I are indicated to be non-
phytotoxic at efective doses in ~lants subject to such
fungi and are further indicated to be of particular
15intcrest as al.go actlny to combat fungi by systemic
action as deterrnined, for example, in tlle combatting
of Vromyces a~p diculatus on beans.
Additional tests analogous to Test Method C at 13,
-; 50 and 200 ppm a.i. sho~7, except ~7here indicated, a lOO~o
20control with the compound o~ Example 1 hereinafter at at
least one test dosage on the following: Phytophthora
cactorum ~maximum control 45~0); Ph~tophtllo1^a c~namom
(maxirnum control 65%); Aphanomyces euteiche~; Stereum
pur~ eum; Thielaviopsis basicola; Pirlcularia ~zae;
___ ._____ __ _ _ _ _
25 and Colletotrichum linde~uthianum (maximum control 90%)
Additional tests analogous to Test Methods A and B
at doses of 32, 125 and 5~0 ppm a.i. conducted ~7ith the
'' 1718~6
- 18 - 136-6878
co~pound of Ex~lple 1 hereinafter show bv spray a~pIi-
cation a 75%,95~and lOO~o control, respectively of
Helminthosporium on barley with 20~ phytotoxicity at
the higher dose.
Tes-t Method D: In vi~o, em~lovin~ Rhi~octonia solani.
The fungus is cultivated in a sterile mixture of Zonolite
and corn meal (10:1 w/w) to whicn water is added in a
ratio of about 1:1 (w/w); cultivation lasts for 14 days
at 25C. The fungus is then mixed into a semi-sterile
10 mixture of peat and sand which then is treated with a
suspension containing the formulated active ingredient to
give concentration of 10 to 160 ppm (e.g. 10, 40 and
160 ppm) calculated per volume substrate. The substrate
is transferred to pots of 5 c7n di~neter which are ~lanted
15 with cotton seedlings (cotyledonous stagej. The planted
- pots are incllbated at 24C and 60 - 70~ relativ~ hurnidity
in an incubatiorl cha~ber for 14 days, after whlch disease
; attack is determinecl by comparing the unyal attack
on roots and hypocotyl with that on untreated, similarly
20 lnoculated check plants. The compound~ of formula I
provide good control in test D. The compound of ~xample
1, hereina~ter, used in the wettable powder formulation
given ahote, provides for example 100% disease control
with no phytotoxicity at the lower dose.
In 2 test analo~ous to ~'est l~ekhocl D run with Phoma
hetae on sugar heet, the cornpouncls of formula I, e.~. khe
cornpounds of forrnula 1, 1~, lE, lC, 2A, 2B, 2~, 2N, 2P,
~ ~71~66
- 19 - 136-6878
2R, 2T, 2Y, 2Z, 2~-1, 2~-~, 2Z-7, 2Z-8, 2Z-11, 2Z-15,
2z-32, 2z-33, ~Z-3~ and 2Z-41 provide good control.
From the foxegoing it will be evident to those
skilled in the art that the compounds of the present
5 invention are also indicated to be of parti.cular i~terest
with regard to the control OL iln.portant soil- and seed-
borne funyi, e~g. _ lmin~,ho~por _ n, Phoma, ~hizortonia
and Thielavio~sis, in addition to thei.r considerable
_ __ _ __
interest and value in the control of po~dery milde~s
lOand rusts.
The particular value and advantages of the invention
are cGnfirmed and/or further indicated in more detailed
evaluat,ions of the co~pound of Example 1 herein~
after ~7hi.ch exhibi.ts the following outstanding and in sore
15cases remar~able pro~erties: 1) a persistency of action
that still produces 100~ control of Ur r.~ . on pole
beanr~ at spray concentrations of 0.012~ on a~p:lication
8 days before inoculation; 2) a good stability of a~ueous
r~pray .suspenr.ions as ind.icated by 100So control of Uroryc,es
20app, on pole beans on application 3 days after preparation
of the suspension (0.012~ concentrati.on); 3) rapid and
lastlng penetration of the active substance into leaves oE
plants to be protected as indlcated by 100% control at
the 0.012% concentration afteJ: a) washin~ the leaves of
25pole beans for 10 rinuteC only 10 minutes after
application of the act.ive ingredient fol~o~ed by infest,a-
- ~ i71866
- 20 - 136-687
tion with Uromyces ~EP ~ b) washing the leaves of grape-
vine for 15 minutes 2 hours after app]ication of the
active irgredient followed by infestatioll with Un nula,
c) simulated rain washing of the leaves of coffee plant~
5 at a rain rate of SO MM/hour first applied t~o hours
after application of the active inyredient for 15 minutes
followed by drying, a second application of rain for
15 minutes again foLlowed by drying and then a third
application of rain for 15 minutes, followed by infesta-
10 tion of the coffee plant with ~emileia vastatrlx, and d)simulated rain washing of the leaves of pole ~eans at a
rain rate of 50 MM/hour first applied 2 hours arter
applicati.on of the active ingredient for 10 minutes
ollowed by dryiny, a second application of rain for
15 10 minutes again followed by drying and then a third
application of rain for lO minutes, followed by
infestation of pole bean plants with Uromyces app; and
4) outstanding systemicity of action involving transport
after uptake through the leaves of the upper or lower
20 portions of grapevine to the other portion whi.ch is
untreated wherehy a 70% and 75~ control of UnclnuLa ln
the untreated upper and lower leaves, respectively, is
observed, lndicatiny that such transport lnto the
untreated leaves takes place both acro- and basipetallv.
25 In still further evaluation of the compound of
Example 1 herelna~ter a rungicidal activi~y of :LOG~ com-
~ ~71866
- 21 - 136-6878
pared with untreated standard is obtained on application
of the active ingred.ient at a concentration of 0.012~
3 days (before sporulation) after pole beans are infested
~7ith IJromyces a~p.
When applied at a concentration of 0.05% onto pole
bean plants already showing sporulation pustules of
Urom~c_s ~Æ~. there is obtained a 60~ control of visible
disease symptoms compared to an untreated control 10 days
after application wi~h a 50% control obtained after only
10 3 days after aoplication. From the foregoing further
evaluations of the compound of Example 1 the desired
prope.rties of a curative activity and at least a partial
eradicative e'-fect are indicated.
Other compounds of the formula I particularly the
15 compounds of Es~.arnples 2A, 2~, 2D, 2E', 2G, 2H, 2L, 2N, 2P,
2Z-1, 2Z-3, 2Z-4, 2Z-7 to 2Z-9, 2Z-11, 2Z-13 to 2Z-15,
2Z-24, 2Z-32, 2Z-33, 2Z-43 to 2Z-45 and 3 hereinafter also shcw very
good to outstallding fungicidal actlvity in evaluation
procedures described above. The fungicidal activity of
20 the compound of Example 2A is for example at least equal
to the activity of the compound of ~s~ample 1 and also
the compound of Example 2Z-33 has the same order of
fungicidal activity as that of Example 1.
~ ~71866
- 22 - 136-6878
Preferred compounds of Lhe formula I have one or
more and preferably all of the following features. a) R
is alkyl of 2 to lO carbon atoms, particularly alkyl of
3 to lO carbon atoms and more particularly alkyl of 3 to
6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms or
cycloalkylmethyl in ,~hich the cyclcalkyl portion is of
3 to 6; b) R is hydrogen, fluoro, chloro, bromo, CF3 or
Cl-C4 a].kyl; c) R' is hyd.rogen, fluoro, chioro, bromo,
Cl-C4 alkyl, Cl-C~ alkoxy, all:ylthio of 1 to 4 carbon
10 atoms, CN,
- yO yO
~ F -~
~herein Y and Y are as above defined; d) R"' i9 hydrogen.
The more prefQrred among the above-mentioned prererred
compounds of the formula I have one or more and prefetably
all of the follo~,liny features:
; 15 a) R ls alkyl of 3 to 6 carbon atoms or cycloa].kyl of
3 to 6 carbon atorns such as cyclopropyl and cyclopentyl;
b) R is hydrogen, fluoro, Cl, ~r, CF3 or Cl-C2 alkyl; and
c) R' is hydrogen~ fluoro, Cl, CN, Cl-C2 aJ.kyl or Cl-C2-
alkoxy; or d) R is hydrogen and R' is
yO O
~ or ~~ ~
201Ocated at the para-pos~tion of Ring A, more preferably
~'~71~66 ~:
,,
- 23 - 136 61378
with Y and Y being hydrogen.
The particularly preferred compounds of the formula
I are indicated to be those in which R is propyl or
butyl, e.g. n-propyl, isopropyl, n-butyl, sec.-butyl,
i-butyl and t-butyl, especially n-propyl, isopropyl,
the branched butyls and most especially t-butyl. Other
branched a].kyls of 5 to 6 carbon atoms, e.~. iscpentyl
and neopentyl, are also indicated to be of parti.cular
interest. Also of particular interest are those in ~hich
10 R is cyclopropyl, cyclopentyl or cyclohexyl.
The following examples further illustrate he present
invention. All temperatures are in centigrade.
I 171866
- 24 - 13G-6878
EX~`~PLE 1
~-t-butyl-~lp-methyl~henvl)-l~ 2~4-triazole-l-ethan
A 0.62 g portion of 61.4~ sodium hydride is washed
three times with petrole~m ether and then lo ml of
dimethylformamide is added ~7hile maintaining stirring. To
5 the resulting suspension is added slowly with stirring
; 1.1 g of triazole in 10 ~1 of dimethylforma~ide followed
by stirring at 20 until bubbling ceases. To the
resulting mixture is then added 3.0 g of 2-(t-butyl)-2-
(4-methylphenyl)-oxirane followed by heating with stirring
lOat 9~ for 6 hours. The resulting reaction mixture is then
poured onto water, extracte~ with ethyl acetate, dried
and chromatocraphed over silica gel while eluding with
hexane/chloroform (50:50) to obtain a yello~7 oil which
crystallizes on stand.ing to a solid which on recrystal-
15lization from ethanol yields a-t~butyl-a-(p-methylphenyl)-
lH-1,2,4-triazvl~-1-ethanol, m.p. 69-71. 'r~e correspond-
ing h~drogen oxalate (Example lA) has a m.p. of 1~7-150,
the p~neth~lbenzene sulfonate (Example 1~) a m.p. æ 21~-220 and the
hvdrochloride (E ~ ?1e lC) a m.~?. of 247-250, and the scdiu~nethanolate
20 of the ~tle c ~ ound a m.p. of > 250 (Example lDI.
EX~MPLE 2
Following the procedure of Example 1 the followi.ng
additional compounds of the invention are obtained:
A) a-t-butyl-a-(p-ch].orophQnyl)~lH-1,2,4-tria~ole-
l-ethanol, m.p. 114-115.
2S Bj a-t-butyl-a-(o,p-~q.tchlorophenyl)-lH-1,2,4-tri-
t 171866
-25- 136-6878
azole-l-et~allol, m.p. 63-64.
C) a-t~butyl--(m,p-dichlorophenyl)-lH-1,2,4-tri-
azole-l-ethanol, m.p. 156-157.
D) ~-t-butyl~a-phenyl-lH-],2,4-triazole-1-ethanol,
5 m.p. 84-86.
E) a-n-decyl-a-(p-methylphenyl)-lH-1,2,4-trla201e-
l-ethanol.
F) a-t-butyl-a-(p-fluorophenyl)-lH-l 2,4-triazole-
l-ethanol, m.p. 104-106~
10 G) a-t-butyl-a-(p-methoxyphenyl)-lEi-1,2,a-triazole-
l-ethanol, m.p. 76-79.
H) a-n-butyl-a-(o,p-dichlorophenyl)-iH-1,2,4-tri-
aæole-l-ethanol, m.p. 109-110.
I) ~-n-propyl-a-(p-chlorophenyl)-lH-1,2,4-triazole-
l-ethanol.
~ a-l-butyl--(p-chlorophenyl)-lH-1,2,4--trlazole-
l-ethanol.
K) a-methyl-a-(p-chlorophenyl)-lH-1,2,4~triazole-
l-ethanol .
20 L) a-t-butyl-a-(p-biphenylyl)-lH-1,2,4-triazole-1-
ethanol, m.p. 117-118.
M) a~t-butyl-a-(m,p-methylenedioxyphenyl)-lE~-1,2,4-
triazole-l-ethanol.
N) a~t-butyl-a-(~-cyano~Jhenyl)-lH-1,2~4-triazole-
l-ethanol, m.p. 123-124.
t 0) a-t-butyl-a-(m-nitrophenyl)-1~-1,2,4-triazole-1-
ethanol .
P) ~-t-butyl-a-(p-phenoxyphenyl)-1~l-1,2,4-triazole-1-
.,
1 171866
- ~6 - 136-6878
ethanol, m.p. 112--113.
Q) a-methyl~ (m~p-dichlorophenyl)-lH-1,2,4-tri-
azole-l-ethanol, m.p. 97-95.
R) -n~propyl-a-phenyl-lH-1,2,4-triazole-1-eth2nol,
m.p. 81-83.
S) a-ethyl-a-(p-chlorophenyl)-lH-1,2,4-triazole-1-
ethanol, Jn . p . 108-109.
T) a-n-butyl-a-phenyl-1~-1,2,4-triazole-1-etllanol,
m.p. 67-68.
U) a-isopentyl-a-phenyl-lH-1,2,4-triazole-1-ethaIlol,
m.p. 78-80.
V) a-n-propyl-a-(p-methylphenyl)-lH-1,2,4-triazole-
l-ethanol, m.p. 86-88.
W) a-methyl-a-(p-methy].phenyl)-lH-1,2,4-triazole-1-
ethanol, m p. 78-80.
X) a~n-pentyl-a-phenyl-lH-1,2,4-triazole~l-ethanol,
m.p. 89-90.
Y) a-isopropyl-~-phenyl-lH-1,2,4-triazole-1-ethanol,
m.p. 71-73.
Z) a-n-butyl-a-(p-chlorophenyl)-lH-].,2,~-triazole-1-
ethanol, m.p. 108-109.
Z-l) a-n--butyl-a-(p-methylphenyl)-lH-1,2,4-triazole-
l-ethanol, rn.p. 79-80'.
Z-2) a-methyl-a-(m-tri~luoromethylphenyl)-lH-1,2,4-
trlazole-l-ethanol, a~ an oil.
Z-3) a-t-butyl-a ~mtri~luoromethylphenyl)~].II-1,2,4-
triazole-l-ethanol, m.p. 120-122.
~ 171866
-27- 136-6878
~ -4) a-t-buty~-a-(m-methylphenyl)-lH-1,2,4-triazole-
l-ethanol, m.p. 93-94.
Z-5) -t-butyl-a-(o-met.hylphenyl)-111-1,2,4-triazcie-
l-ethanol.
Z-6) a-t-butyl-a- (p-t-butylphenyl)-lH-1,2,4-triazole-
l-ethanol, m.p. 1~8-llo~.
Z-7) a-t-butyl-a-(p-ethylphenyl)-lH-1,2,4-triazole-
l-ethanol, m.p. 91-g4.
Z-8~ a-t-butyl-a-(m-phenoxy~henyl)-lH~1,2,4-triazole-
10 1-ethanol, m.p. 133-135.
Z-9) a-t-butyl-a-(m-methoxyphenyl)-lH-1,2,4-triazole-
l-ethanol, m.p. 59-61.
Z-10) -t-butyl-a-(p-trifluoromethoxyphenyl)-lH-1,2,4-
triazole-l-ethanol.
Z-ll) ~-cyclohexyl-a-(p-methylphenyl)-lH-l~2~-trlazole
: l-ethanol, m.p. 102-103.
Z-12) a-hexyl-a-(p-methylphenyl)-lH-1,2,4-triazole-
l-ethanol.
Z-13) -octyl-a-(p-methylphenyl)-lH-1,2,4-triazole-
20 1-ethanol, m.p. 79-81.
Z-14) a-dodecyl-a-(p-methylphènyl)-lH-1,2,4-triazole-
l-ethanol, m.p. 78-79.
Z-lS) a-t-butyl-a-(p-bromophenyl)-lH-1,2,4-triazole-
l-ethanol, m.p. 124-125~.
Z-16) a-neopentyl-a-(p-methylphenyl)-lH-1,2,4-triazole-
l-ethanol.
Z-17) a-sec.-butyl-a-(p-methylphenyl)-].H-1,2,4-triazole-
--` ~1718~6
- 28 - 136-6878
l-ethanol.
Z-1.8) a-(1,1-dimethylpropyl)-a-(p-metllyl~henyl)`-1H-1,2,4-
triazole-l-ethanol.
Z-19) -t-butyl-a-(m,m-dibromophenyl)-lH-1,2,4-triazole-
5 l-ethanol.
z-20) a-cyc1opropyl-a-(p-m~thylphenyl)-lH-1,2,4-triazole-
l-ethanol.
Z-21) a-(2-methylcyclopropyl)-a-(p methylphenyl)-lH-1,2,4-
triazole-l-ethanol.
Z-22) a-cyclohexylmethyl-a-(p.methylphenyl~ lH-1,2,4-
triazole-l-ethanol, m.p~ 7~-81.
%-23)a-cyclopentylmethyl-a-(p-methylphenyl)-lH-1,2,4-
tr~.azole-l-ethanol, m.p 74-76.
Z-24) a-(1-ethylpxopyl)-a-(p-methylphenyl)-lH~1,2,4-tri-
l5azole-1-ethanol, m.p. 87-89.
Z-25) a-(1-meti-ylbutyl)-a-(p-methylpheny].)-lH-1,2,4-tr.i-
aæole-1-ethanol.
Z-26) a-t-butyl-a-(~-bromo-p-methylphenyl)--lH-1,2,4-tri-
azole-1-ethanol, m.p. 155-158.
20 Z-27) -t-butyl-a-(m-fluoro-p-methylphenyl)-lH-1,2,4-tri-
azole-l-ethanol, m.p. 102-104.
z-28) -t-butyl-a-(m-chloro-p-methylphenyl)-l~i-1,2,4-
triazole-l-ethanol, m.p. 144-147.
Z-29) a-t-butyl-a-(m-chloro-m-J,~ethoxypilenyl)-lI-i-1,2,4-
25 triazole-l-ethanol.
Z-30) a--t-butyl-a-(p-tri.fluoromethyl-m-~hlorophenyl)-lH-
1,2,4-triazole-1-ethanol.
- t 171~6~
- 29 - 136-6878
Z-31) a-t-butyi-a-(m-chloro-m-phenoxyphenyl)-lH-1,2,4-
triazole-l-ethanol.
z-32) a-cyclopentyl-a-phenyl-lH-1,2,4-triazole-1-
ethanol, as an oil.
z-33) a-cyclopropyl-a-(p-chlorophenyl)-lH-1,2,4-tri-
azole-l-ethanol, as an oil.
Z-34) a-cyclobutyl-a-(p-~luorophenvl)-lH-1,2,4-triazole-
l-ethanol, m.p. 83-84.
Z-35) -t-butyl-a-(m,p-dimethylphenyl)-lH-1,2,4-triazole-
10 l-ethanol, m.p. 120-122.
Z-36) a-t-butyl-.(o-methoxy-m-methylphenyl)-lH-1,2,4-
tr.iazole-l-etnanol.
z-37) a-t-butyl-a-(o-methyl-p-methylthiophenylj-lH-
1,2,4-triazole-l~ethanol.
15 Z-38) a-t-butyl--(m-methyl-p.phenoxyphenyl)-lH-1,2,4-
triazole-l-ethanol.
; Z-39)- a-t-butyl-a-(o-methyl-m-nitrophenyl)-lH 1,2,4-
i triazole-l-ethanol.
Z-~O)a-cyclobutyl-a-phenyl-lH-1,2,4-triazole-1-ethanol,
20 a~ an oil.
Z-41) a-sec.-butyl-a-(p-chlorophenyl)-lH-1,2,4-triazole-
1-ethanol, as an oil.
Z-42) a-t-butyl-a-(m,m-dichlorophenyl)-lH-1,2,4-tri-
azole-l-ethanol, m.p. 145-147
Z-43) -t-butyl-a-(m-chlorophenyl)-1~l-1,2,4-triazole-
l-ethanol, m.p. 126-127
Z-44) a-t-butyl-a-(p-cyanophenyl)-lH-1,2,4-triazole-
~; .
.,
' 171~66
- 30 - 136-6878
l-ethanol, m.p. 105-107.
Z-95) a-cyclopentyl-a-~p-methylphenyl)-lH 1,2,4-tri-
azole-l-ethanol.
Z-46) ~-isobutyl-a-phenyl-lH-1,2,4-tria701e-l-ethanol.
5 z-47) a_(l-methylcyclopropyl)-a-p.methylphenyl-lH-1,2,4-
triazole-l-ethanol, m.p. 126-128.
Z-48) ~-methyl-~-(p-biphenylyl)-lH-1,2,4-triazole-1-
ethanol, m.p. 115-120.
Z-49) ~tert.butyl-~-(p-iodophenyl)-lH-1,2,4-triazole-1-
10 ethanol, m.p. 78-80.
Z-50) ~-(3-heptyl)-~-(p-methylphenyl)-lH-1,2,4-triazole-1-
ethanol, oil.
Z-51) ~-(2-pentyl)-~-(p-methylphenyl)-lH-1,2,4-triazole-1-
ethanol, m.p. 89-91.
Z-52) ~-(tert.butyl)-~-(mlml-dimethylphenyl)-lH-l~2~4
triazole-l-ethanol, m.p. 128-130.
Z-53) a-tert.butyl-~-(3-nitro-4-methylphenyl)-lH-1,2,4-
triazole-l-ethanol, m.p. 160-161C.
Z-54) ~-tert.butyl-~-(3,5-dinitro-4-methylphenyl)-lH-1,2,
204-triazole-1-ethanol, m.p. 194-196C.
,, , . .. ,,, . , . .. . . , . , . . , - ~ ~ , ,
~ l 7186~
- 30a -
EXAMPLE 3
a-t-butyl-~-(p-carboxyphenyl) -lH-l, 2, 4-triazole-l-
ethanol, and potassium salt
A mixture of 1.3 g of a-t-butyl-a-(p-methylphenyl)-
lH-1,2,4-triazole-l-ethanol, 1-89 g of potassium permang-
nate and l9 ml of water are refluxed with stirring for
l hour. The resulting reaction mixture is filtered while
still hot, the residue washed with 10 ml of hot water,
the filtrate treated with charcoal and concentrated
in vacuum to a small volume (4 ml) which is dried under
high vacuum to obtain the potassium salt of a-t-butyl-a-
(p-carboxyphenyl)-lH-1,2,4-triazole-1-ethanol, m.p. 194
, (decomposition).
; The above reaction is repeated using three times the
amounts of the materials specified above except that the
filtrate i8 washed with ether, the ether washing washed
with water, the combined aqueous layers acidified with
concentrated hydrochloric acid with stirring until no
additional precipitate formed, and the precipitate
~0 collected by filtration, washed several times with ether
and dried under a high vacuum to obtain ~-t-butyl-a-(p-
'~
! l 718~6
- 31 - 1~6-6~78
carbo~yphenyl) -lH-l, 2 4-triazole-1-ethanol m.p. 248-250.
EX~iPLE 4
2-(t-butyl)-2-(4-methylphenyl?-oxirane
A 2.2 g portion of 61.4% sodium hydride is washed
5 three times with petroleum ether then 70 ml of dimethyl-
sulfoxide added and the mixture heated with stirring to
70 and carried to 85 by the exotherm after ~Jhich the
mixture is heated at 75 for 40 minutes. The resulting
mixture is cooled to 0 in an ice/salt bath and then under
lOa nitrogen blanket there is added dropwise a solution of
7.0 g of trimethylsulfonium iodide in 50 m]. of dimethyl-
sulfoxide and 20 ml. tetrahydrofuran while maintaining
the temperature belo" 18. To the resulting mixture is
then added with stirring under the nitrogen blanket a
solution of 3.0 y of t-butyl-p-methylphenyl ketone in
30 ml of tetrahydrofuran whi].e maintaining the temperature
below 10. The resulting mixture is stirred at 0 for 30
minutes and then at room temperature for 2 hours. The
resulting reaction mixture is then poured onto 400 ml
200f water, extracted with me~hylene chloride, the organic
phase ~ashed with water and then brine, dried and
evaporated to obtain a yellow oil of 2-(t-hutyl)-~-(4-
methylphenyl)-oxirane.
7ia66
~ 31a -
EXAMPLE 5
~-(tert.-butyl)-~-~p-methoxycarbonyl-phenyl)-lH-1,2,4-
triazole-l-ethanol
To a flask containing at 0 an ether solution of
CH2N2 prepared in the conventional manner from 3.39 9
of N-methyl-N-nitroso-p-toluenesulphonamide is added
dropwise, while maintaining ice bath cooling, a solution
of 1.5 g of -(tert.-butyl)- -(p-carboxyphenyl)-lH-1,2,4-
triazole-l-ethanol in 85 ml of dry tetrahydrofuran. The
resulting mixture is allowed to stand under ice cooling
until thin layer chromatography analysis shows an essen-
tial absence of the triazole starting material. A few
drops of acetic acid are added to destroy excess diazo-
methane, the mixture is then concentrated to remove
tetrahydrofuran, the concentrate extracted with ether and
washed with 2N NaOH solution. After drying white crystals
are formed on standing. The crystals are recovered by
filtering and recrystallized from CH2C12/ether to
obtain the title compound, m.p. 152-154.
