CA1115714A - Derivatives of n-aryl-1,3-oxazolidine-2,4-diones exerting a fungicidal action, and process for preparing same - Google Patents

Abstract

Abstract of the Disclosure:
Disclosure are N-aryl-1,3-oxazolidine-2,4-diones of formula:
in which R = alkyl C1-C5:
Y = H: halogen: 3,4-dichloro: 3,5- dichloro:
3,5-dibromo: 3,5-dimethyl: 3,5-dimethoxy 3,5-bis-trifluoromethyl: and A = CN: or in which R1 = OH: OR: NH-NHR: N(R)2.
These are useful as fungicides.

Description

'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 .,. . ,. :.. . ~ :

. :

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~
!

. . , : ~ ' .. : :

^-" ll~S714 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.

3,S-dichlorophenYll-5-methYl-5-carboethoxY-1,3-oxazolidine-2,4-dione. _(Compound No. 4 - Table I).
; 30

-4-~ 2 5 -C H OH
ÇOOC2H5 ~ COOC2H5 2 5 NCO ~ OH - ~ ~H

~ t H3C COOC2H5 ~
Cl ~ ~Cl Cl~ Cl ,~ 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 . .

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 :

,. . , , . . . - - , .. . .. . .

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.
'-' \

; \ :

.~ \

, \ :
` \

\

~ --.. - --------- ~
.~ 1~15714 ~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
:
__.___ .. _ .. _ .__~ ._ - 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 .~ ~ , _ ..

~: 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 - ~liS714 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 ~` 20 9 100 100 100 Vinchlozoline (PB 501 (commercial product of reference) 100 95 80 ' ~ i :

.
.
.
, _9_ : .

. : . .. ~ : . .

.. . : , . ~ , :

Claims (10)

The embodiments of the invention in which an exclusive property or privilege is claimed are defined as follows :

1. An N-aryl-1,3-oxazolidine-2,4-dione of formula :
in which.
R = alkyl C1-C5;
Y = H, halogen: 3,4-dichloro; 3,5-dichloro; 3,5-dibromo;
3,5-dimethyl; 3,5-dimethoxy; 3,5-bis-trifluoromethyl;
and A = CN; or in which R1 = OH, OR; NH-NHR; N (R)2

2. A compound as defined in claim 1, said compound being N-(3,5-dichlorophenyl)-5-methyl-5-carbomethoxy-1,3-oxazo-lidine-2,4-dione.

3. A compound as defined in claim 1, said compound being N-(3-chlorophenyl)-5-methyl-5-carboethoxy-1,3-oxazolidine-2,4-dione.

4. A compound as defined in claim 1, said compound being N-(3,5-dichlorophenyl)-5-methyl-5-carboethoxy-1,3-oxazo-lidine-2,4-dione.

5. A compound as defined in claim 1, said compound being N-(3,5-dimethylphenyl)-5-methyl-5-carboethoxy-1,3-oxazo-lidine-2,4-dione.

6. A compound as defined in claim 1, said compound being N-(3,5-dimethoxyphenyl)-5-methyl-5-carboethoxy-1,3-oxazo-lidine-2,4-dione.

7. A compound as defined in claim 1, said compound being N-[(3,5-bis-trifluoromethyl)-phenyl]-5-methyl-5-carbo-ethoxy-1,3-oxazolidine-2,4-dione.

8. A compound as defined in claim 1, said compound being N-(3,5-dichlorophenyl)-5-methyl-5-(n.propoxycarbonyl)-1,3-oxazolidine-2,4-dione.

9. A process for preparing a compound as defined in claim 1, consisting essentially in reacting a phenyl isocyanate havinq the formula:
in which Y has the same meaning as specified in claim 1, with an a-hydroxy-ester of formula:
in which R and A have the same meaning as specified in claim 1 and R2 = OH; OR; NH2, and cyclizing the resulting compound in the presence of tertiary base, according to the reaction:

10. A method of fighting the investations due to fungi in useful plants, consisting essentially in treating the plants with one or more of the compounds, as defined in claim 1, in a solution containing the active ingredient in an amount of from 0.1%? upwards.