Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
1115714
'I'his invention relates to a new class of derivatives of
N-aryl-1,3-oxazolidine-2,4-diones exerting a fungicidal action.
More particularly, it relates to novel N-aryl-1,3-oxazolidine-
2,4~diones substituted in position 5; to a process for preparing
such compounds, and to the utilization thereof for fighting
infections in useful plants due to fungi.
Derivatives of N-(3,5-dichlorophenyl)-1,3-oxazolidine-
2,4-dione substituted in position 5 by two alkyl groups or by a
hydrogen and an alkyl group, and exerting a fungicidal activity,
are described in Dutch patent application No. 68/17249 of
Sumitomo Company. According to BASF's French patent application
No. 2,172,295, such compounds seem to have only a weak fungicidal
activity, wherefore BASF describes derivatives of N-(3,5-dichloro-
phenyl)-1,3-oxazolidine-2,4-dione having in position 5 two
substituents, one of which consists of H or alkyl, and the other
of which is alkenyl, or both together representing a methylene
group. It is known furthermore that the most representative
compound among those described in the aforesaid Dutch patent
application No. 68/17249, i.e, N-(3,5-dichlorophenyl)-5,5-
dimethyl-1,3-oxazolidine-2,4-dione, available on the market ;
under the trademark Sclex, has prejudicial secondary effects on
humans.
On the other hand, the compound according to French
patent application No. 2,172.Z95, i.e. N-(3,5-dichlorophenyl)-
5-methyl-5-vinyl-1,3-oxazolidine-2,4Tdione (trademark:
,~ Vinchlozoline), exhibits some difficulties in the synthesis
which are connected with the necessity of preparing a ,13-
unsaturated lactate.
'I'he necessity of finding new compounds economically
7 30 advantageous and efficient in defending important agrarian
cultures from the attack of pathogenous fungi is the main
reason for continuous and intensive research work in the field
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1~15714 ` - -
of the N-aryloxazolindiones.
We have now found a new class of oxazolidine derivatives
which are endowed with excellent fungicidal properties.
Accordingly, it is a principal object of the present
invention to provide new N-aryl-1,3-oxazolidine-2,4-diones
differently substituted in position 5, and particularly such
N-phenyl derivatives.
Another object is that of providing a useful method of
preparing such compounds.
A further object is that of establishing the fungicidal
activity thereof.
The compounds of the present invention have the general
formula
~ , `,
Q ~
~ ~ ~0
~ I
Y ~ ,:
20~ wherein:
R ~ alkyl Cl-C5;
Y = H; halogen; 3,4-dichloro; 3,5-dichloro;
3,5-dibromo; 3,5-dimethyl; 3,5-dimethoxy; 3,5-bi~- `
trifluoromethyl: and -
A = CN; or a-Rl in which Rl = OH~ OR; NH-NdR: N(R)2.
Among the compounds which have proved so far to be the
:' .
most interesting are those recorded in the following ~able I:
TABLE I
~ ~ _ Rl
0',
y~ '.
A
.. . . . .. . ..
.
157~4
o ~ o o o ~ 0 ~ O
~ N O ~ d' N O!) I~ d~ ~1 00 r I ~S) d~ li') ~) d~
O r) 1-') d' ~ d' d' d' ~ ~ ~1 d' d' d' ~) d' d'
~ ':
. N O O N N 0 1~) r-l 10 Ll~ 11~ 11~ (~) d~ O O
U ~) ~ r` N N 0 ~ Lr) O O O O n ~ ~ d'
~ ~ In ~ ~ d' ~ d' ~ ~ d' d' d' ~.) d' ~ d' d' '
U
U~
H ~ O ~) d' N O O O ~n d' ~ t-- d' 0 d'
~q ~ ~ ~
~ ~ ,................. ..... ..
O d' d' d' ~) ') U) u~ ) Ir) N N
. oD ~ ~D d' d' O O oo ot) o~
.1~1 U C~ o o ~ ~ <~
F~ ~ a ~ d' d' ~7 ~ ~ ~ ~) f~) r~) In ~ N
~ U
. . ~
~) N Ifl N O O d' 0 C~\ d' d' ~ O ~
~` 0
~ 1 .................. ........
O 0 0 N r~ ~ N l~l 0 15~ 0 0 d' Itl 1
. ~ 1 o ~) 0 0 0 d~
~1 d' d' O o 0 1` u~
tr~ CJ) N t~l 1~ i-- ~iu ) 0 0 0 O ~ L~
U ~
I ~ ,1
-l~rl c 'o' ~o
O t~ O O O N
N (S~ cn
. ~ I I I I I ~I I I I I I I I I I
P~ U ~ 0d' (~1 0 N O ~) O11~ N 0 0 1"
. ~ O ~0 ~ O 1~ ~1~1 ~1 ~1` ~ ~~1 ~ N
. O
u~ C~
m$ $ ~ $ $ $ ~ $ m $ m m
~ ~ ~ N N N N N N ~ ~ ~) ~) N ~ N~1
. U~. Ul
: ~1 P~ ~ ~ ~ ~ ~i ~) ~ ~ $ ~ ~) ~
m ~ ~ ~ N~ ~ m
: ~ ~ ~, c~ c~ c~ u ~ c~ U C~ C~ ~ $ ~ m m c
. H
,~ E~
m N N
- ~ ^ ~ N ^ N
' c/~ ~) $~ $('~) ~
. ~ ~ N~ ~j r;) ~4 N NN ~ C~ 14 t~l ~1
~1 ~I C~ ~ C~ I O O C)
C~ C) ~ ~ ~ ~.) C~ C~ ~ ~ ~ U
~1 ~ I I I I I I I I I I I I I
$
O O ~1 ~ ~) ~ ,r, ~ r` 0 (S~ O ~ N ~) d' In ~D
0~ r-l ~I 'I ~ 'I 'I 'I ~
C~
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The method of preparing such compounds--and this is a
further object of the invention--consits or consists essentially
in reacting ~-hydroxy-esters or analogs thereof having the
general formula : OIH
O~ ¦ (II)
R -C-C-A
(in which A and R have the same meanings as specified above in
general formula I, R2 = OH, OR, NH2), with an arylisocyanate inthe
presence of a tertiary base, which favors the ring-closing of
the carbamate intermediate.
The reaction is schematically the following: ~
O C - A
.I i ;
o ~,c 5~o
O - C _ A
¦ N
~ t ~-C-~ Y
'~ The a-hydroxy-esters of the general formula II are
derivatives easily obtainable from inexpensive raw materials.
he compounds of the general formula I are endowed with
a high fungicidal action, which is superior to that of the N-
3,5-dichlorophenyl)-1,3-oxazolidine-2,4-diones already known
(see Tables II, III, IV).
.
~ The following examples are given to still better illus-
-~ trate the present invention.
EXAMPLE 1
3,S-dichlorophenYll-5-methYl-5-carboethoxY-1,3-oxazolidine-
2,4-dione. _(Compound No. 4 - Table I).
; 30
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15714
CH3
~ 2 5 -C H OH
ÇOOC2H5 ~ COOC2H5 2 5
NCO ~ OH - ~ ~H
~ t H3C COOC2H5 ~
Cl ~ ~Cl Cl~ Cl
ICH3
,~ cooC2Hs
~ N ~
/~
` C ~ Cl
37.6 g of 3,5-dichlorophenyl-isocyanate and 38 g of
diethylic methyl-tartronate ~diethyl ester of 2-methyl-2-hydroxy- ~-
malonic acid) were dissolved in 1 liter of benzene. ;
The resulting solution was stirred at room temperature
for 3 hours whereupon, after addition of 1 ml of triethylamine,
it was heated at reflux for 12 hours. This was then filtered
and the solvent was evaporated at reduced pressure. ^
The solid residue was re-crystallized from ethyl
20~ ~
alcohol. 45 g of product were thus obtained (white needles, ~,
m.p. = 109-110C).
(By an analogous procedure, the remaining compounds
indicated in Table I were synthetized).
:: i . .
EXAMPLE 2
Biological activity of the compounds of this invention
a) Activity in vitro.
~ ; The activity was determined by evaluating the percentage
I ~ of growth of the fungi cultivated in soil containing increasing
amounts of the compounds being ~ested. Such compounds were in-
troduced into the culture medium in the form of dispersions with
dimethyl sulphoxide + Tween 20, so as to have a final concentration
:
,. . , , . . . - - , .. . .. . .
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of 0.5% in dimethyl sulphoxide and 0.01% in Tween 20.
For the species of fungi such asBotrytis cinerea,
Monilia fructiqena, Penicillium italicum and Asper~illus
Parassiticum, 1 drop of a suspension of spores and mycelium was
put in the center of Petri capsules containing agar-treated
soil (PD Agar Difco), thus obtaining a circular inoculum.
After a 4-day growth at 25C the diameters of the colonies which
had developed were measured, and the percentage of growth inhibi-
tion in respect of the untreated checks were calculated.
For the species Helminthosporium Maydis, Helm nthosporium
orvzae and Alternaria tenuis, lOO,ul of a suspension of spores
and mycelium were introduced into tubes containing 10 cc of
potato broth (Difco), which were kept horizontally and in
incubation for 7 days at 25C. After such incubation period and
after intense agitation, the percentage of growth inhibition of
the fungi was calculated by placing the tubes vertically and
close to one another.
The result obtained are recorded below ln Table II.
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~n ~ o o o o o o
,~ o o o o
~ C ,~
_ . _ __
.~
o
o o o o o o
~ o o o o o 1` o
~rl ~ r-l r-l r-l r1 r-l
r~ ~ U~
m _
.~
o~
~ ~ o 80 o ~ o
.,,
~ ~ U~
s~ ~ ~ ~
~ ~ ~ .
.~ ~
~ ~ .
H ~,~ ., ~ O O O O O O
H ~ h o o o o r--
~ P ~ ,~ a a
E~ ~1 , .
~ ._ ~ ._ . , .. _ _ .. _ ~ ~ o
r ~ H ~ ~ N ....
. .~ ~: X ~ ~
rl a~ ~ u
r-ll ~ O O O O O O .~
~ . O O O O CO O ~ U~ ~ ~
U ~ O = O =
P~ X ~ X
U r~ ~0 r~
,: r~ .
rl E3 O O O O O O ~V U ;'V~ U
r~ O O O O O O
. ' ~ u- . I O L~ O
~ U r1 U ,~ U
E~ o o o o o o ~I) (I)
~ o o o o o o ~ ~ ~ a
m Ir ,~ o~ p P~ 'p
... .. _.~ .... __ ~_. ,,_ ,~ C
U~ ~ ,~ r~ ~ r~
.. _ U s~ U
V P~ ~V P'
~o .~ I ~
... _. _ . _.___ _ _ ___._ _ _ . 5. _._ _ _ _. ___. _ -.` - -----' - ,_. ~_~ _ . r~ ~ r~
'-V ~ o t~ ~ tll ~)
~ X
0~ r~ ~ ~U
:
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- 11157~4
b) Preventive activity aqainst BotrYtis cinerea on tomato plants.
soth leaf faces of tomato plants cv. Marmande, cultivat-
ed in pot in a conditioned environment at 25C and 60% relative
humidity, were sprayed with a hydroacetonic solution at 20% of
acetone (vol./vol.) of the products being tested, until the
leaves are uniformly wet.
After one day artificial infection was effected by
inoculating a suspension of Botrvtis cinerea in carrot broth
(1,000,000 of spores/cc) into both leaf faces. After a 24-hour
residence period in a humidity-saturated environment at 26C,
the plants were transferred into an environment at 26C and 70%
relative humidity for the duration of the incubation period
(6 days).
Finally, the seriousness of the~infection was visually s
evaluated according to indices on a scale of measure ranging
from 100 (sound plant) to 0 (thoroughlyinfected plant).
The results obtained are recorded below in Table III.
Table III
Preventive fungicidal activity against Botrytis c. on tomato
plants
~ .
Compound No. Concen- _
: : tration %~ 3 1 5 O.75 0.37
.~ ~ , _ ..
4 100 100 100 95
16 100 100 100
~: Sclex (PB 50) 100 97 96 80
~reference commercial product) .
Vinchlozoline (PB 50)
(reference commercial product) i 00 100 95 80
:
c) Preventive activity aqainst Plasmopara viticola on vine plants.
The leaves of vine plants cv. Dolcetto, cultivated in
pot in a conditioned environment at 25C and 60% relative
. humidity, were treated by spraying both faces of same with the
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products being tested in a hydroacetohic solution (20% of acetone
vol./vol,), until the leaves are uniformly wet.
24 hours after the treatment, the lower faces of the
leaves were sprayed with an aqueous suspension of conidia of
Plasmopara viticola (200,000 conidia/cc).
After a 24-hour period of residence in a humidity-
saturated environment at 21C, the plants were transferred to
70% relative humidity at 21C for the incubation period (7 days).
Finally, the intensity of the infection was evaluated
according to indices of an evalutaion scale ranging from 100
(sound plant) to 0 (fully infected plant).
The results obtained are recorded below in Table IV.
Table IV
_ _
Preventive fungicidal activity against Plasmopara viticola on
vine plants.
!
Compound No. Concen- _
_ tratian, /Oo 1 O.S 0.1
2 100 100 100
7 100 100 100
~` 20 9 100 100 100
100 100 100
11 100 100 100
13 100 100 85
Vinchlozoline (PB 501
(commercial product of reference) 100 95 80
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