CA1113385A - Fungicidal 3-(n-acyl-n-arylamino)-gamma- butyrolactones, gamma-butyrothiolactones and gamma- butyrolactams - Google Patents
Fungicidal 3-(n-acyl-n-arylamino)-gamma- butyrolactones, gamma-butyrothiolactones and gamma- butyrolactamsInfo
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- CA1113385A CA1113385A CA295,281A CA295281A CA1113385A CA 1113385 A CA1113385 A CA 1113385A CA 295281 A CA295281 A CA 295281A CA 1113385 A CA1113385 A CA 1113385A
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Abstract
Abstract of the Disclosure Novel 3-(N-acyl-N-arylamino)-gamma-butyrolactones, thiobutyrolactones and butyrolactams are useful for controlling and for eradicating fungi, particularly plant fungal infections.
Description
~3~ 35 1 ' DESCBIP~ION_OP`_THE_PRIOR_ART
2 U. SO Patent No., 3,9~3,860, issued to David Cheong King
3 Chan on Janua~y 25, 1976, a~d U.S. Pat2nt NoO 4~r012~519~ issued
4 to David Cbsong ~inq Chan on Mzrch 15, 1977, disclose the use of a large class of 3- (N-acyl-N-arylamino~ lactones and 3-SN-acyl-N-6 arylamlno~ lactams a~ protectan~ fungicides., - 7 U.S. Patent No. 4,034,10~, issued July 5, 1977, to H.
8 Moser, and U,.~S. Patent No. 4,015,648, i sued May 24, 1977 to H.
9 Moser, disclose the use of N- (methoxycarbonylethyl) -N haloa~ etyl-anilines zs preventive and curative fungicides.
11 German Patent Publica~ion Nos. 29643,403 and 2,643,44S, 12 puhlished April 7r 1977~ disclose the use of ~I~(alkylthio-13 carbonylethyl)acetani1ldes for controlling funyi, particularly 14 those of the class P_ycomycete~
Netherlanas Patent Publicatio~ ~lo. 152, 849, published 16 .april~ 15, 197~7, discloses ~the; use of N-lal3soYymethyl~ acetaniliaes -~ 17 as fungicides.
18 ~ ~ F~ Jo Sch~inn, T. Staub and PO Vrech, 29 Inter~at.
19 symposium Uber Pflanze~schutz,t Gent., ~1977 ~Bisannu~l German Crop Protection ~eeting, 1977), disclose N-~2~6-di~ethylphenyl)-N-(2'-21 methoxyacetyl)-alanine methyl ester for the control of -22 Ph~oE!hthor- afestgns, P1asDoPara vit__ola and Pseudo~erono~o~a 23 humili.
24 SUM~APsY OF TH~ INVEN~ION
--_ __ _ It has n~: been fouDd that 3- (N-acyl-N-arylamino~ -76 gamma-butyrolacton2s, butyr~thiolactones and butyrolactams are 27 effective for the control of fungi, e~p~cially for downy milde~ '.
28 fu~gal infection caused by fungal species of th~e Peronos~o_ac~eae .
29 fa~ily and late blight fungal infection caused by PhYto~t~ora 30 ~gfestan~. ~So e of the co~pounds of tha inrention are effective 31 both as prot~ctant fungicides, i.e., they preYent or pr~tect ~ 33~3S ~
.
against fungal infections, and as eradicant fungicides, i. e ., they eliminate and cuEe established infections. The compounds ~.
of the invention are especially preferred for the control of grape downy mildew. .
DESCRI~r~N ~~ T11r ~N~rNlIoN
The compounds of the present invention are within the following hroad classes of compound represented by the Formula (I) : :
O : , : C Rl :
Ar-N \ (I) CH CH . :
Q=C l 5CH-R2 .:
\y/ ;:
wherein Ar is phenyl, naphthyl, or phenyl or naphthyl sub-stituted with l to 4 of the same or different substituents :
selected from fluoro, chloro, bromo, alkyl of l to 4 carbon atoms or alkoxy of l to 4 carbon atoms; Rl is alkyl of l to 6 carbon atoms, hydroxymethyl, halomethyl of l to 3 of the same or different halogens selected from fluoro, chloro or bromo, alkan-oyloxymethyl of l to 6 carbon atoms, alkoxymethyl of l to 6 car- ;
bon atoms, alkylthiomethyl of l to 6 carbon atoms, phenylthio-. .
methyl, phenoxymethyl, phenylthiomethyl or phenoxymethyl sub- ;~ :
stituted on the phenyl ring with l to 2 of the same or : different substituents selected from fluoro, chloro, bromo, alkyl ;~
of l to 4 carbon atoms or alkoxy of l to 4 carbon atoms, phenyl, phenyl substituted with l to 4 of the same or differen~ sub-stituents selected from fluoro, chloro, bromo, alkyl of l to 4 ~ ~:
carbon atoms or alkoxy of l to 4 carbon atoms, halovinyl of l to ~ ~:
~.,, ~ ~ ~ 3 ::
3 of the same or different halogens selected from fluoro, chloro :
or bromo; and R is hydrogen, chloro, bromo, alkyl of 1 to 6 carbon atoms, phenyl or phenyl substituted with 1 to 2 of the same or different substituents selected from fluoro, chloro, bromo or alkyl of 1 to 6 carbon atoms; and Y is O/ S or N-R
wherein R is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 3 to 6 carbon atoms, phenyl, phenyl substituted with 1 to 4 of the same or different substituents selected from fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon ~:
atoms, with the proviso that when Ar is phenyl or substituted phenyl as described above and Rl is alkyl, halomethyl, phenyl, halovinyl or substituted phenyl as described above, then Y is not :: ~
o or NR. ^:
In particular, the present invention provides a method or the control of fungi which comprises contacting said :
fungi or their habitats with a fungicidally effective amount of a compound of the formula :
~1 ' C_Rl Ar-N (I~
7 f 2 ~
O-C OEI-R ::
\0/
wherein Ar is phenyl, naphthyl, or phenyl or naphthyl substituted with 1 to 4 of the same or different substituents selected f~om ` ;~
fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms; Rl is alkyl of 1 to 6 carbon atoms, alkan- ;~
~ .
- 4 - :
3~
oyloxymethyl of 1 to 6 carbon atoms, phenyl, phenyl substituted with 1 to 4 of the same or different substituents selected from fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms, halovinyl of 1 to 3 of the same or different halogens selected ~rom fluoro, chloro or bromo; and R is hydrogen, chloro, bromo, alkyl of 1 to 6 carbon atoms, ~ r phenyl or phenyl substituted with 1 to 2 of the same or different substituents selected from fluoro, chloro, bromo and alkyl of 1 to 6 carbon atoms.
10Preferably, Ar is phenyl or substituted phenyl, or ~;
naphthyl or substituted naphthyl.
Furthermore and preferably R is chloromethyl or alkoxy-methyl and R is methyl.
The above de ined compounds of Formula (IV) are particularly useful for controlling the growth of Phytophthora infestans and Plasmopara viticola.
Representative substituted-phenyl groups which Ar, R
or Rl may represent are 2-fluorophenyl, 2,4-dichlorophenyl, 3,5-dibromophenyl, 4-methylphenyl, 2,6-diethylphenyl, 4-methoxy-~0phenyl, 2,6~dimethyl-4-chlorophenyl, 2,3,6-trimethylphenyl, 2,3,5,6-tetramethylphenyl. Preferred substituted-phenyl Ar groups are phenyl substituted with 1 to 2 of the same or different substituents selected from chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms. Most preferred substituted-phenyl Ar groups are 2,6-dialkylphenyl, especially 2,6-dimethylphenyl.
Representative substituted-naphthyl Ar groups are 1-naphthyl, 2-naphthyl, 1-methyl-2-naphthyl, 4-methyl-2-naphthyl, 4-methyl-1-naphthyl, 2-chloro-1-naphthyl, 2-methoxy~l-naphthyl, 2,4-dimethyl-1-naphthyl and 2~7-dimethyl-1-naphthyl. Preferred ~,,., , ~.
~ . ,.. ,.. , _ ~ .
- 4a -~ `33~
substituted naphthyl A.r groups are 2-alkyl~l~naphthyl groups, ;
especially 2-methyl~l-naphthyl.
Representative halomethyl groups which Rl may repre-; sent include fluoromethyl, chloromethyl, bromomethyl, dichloro-methyl, tribromomethyl and fluorodichloromethyl. The preferred halomethyl Rl group is chloromethyl.
- Representative alkanoylmethyl R groups are acetyl-, methyl, propionylmethyl and hexanoylmethyl.
Representative alkoxymethyl Rl groups are methoxy~
, ` 10 methyl, ethoxymethyll isopropoxymethyl and n-pentoxymethyl.
The preferred alkoxymethyl RL group is methoxymethyl.
~, ;': -' ` ~:, ~;''"' - - 4b - ~i ;
53~;9 1 Representative alkylthiomethyl Rl qroups are ~ethyl-2 thiomethyl, n-propylthiomethyl and n-pe~tyl~hio~ethyl. .
3 Representati~e substitutQd-ph~nylthio~ethyl a~d : 4 substituted-phenoxy~ethyl Rl groups are 4-chlorophenylthiomethylv S 4~methylpheno~ymethyl, 2,4~dichloropheno~y~ethyl, 3,5-dime~hyl-6 phenylthiomethyl and 2-chloro-4-methylphe~oxymethyl1 7 Repre~entati~e alkyl R, R~ ana R2 gr~ups are methyl, 8 e~hylp isopropyl ana n-hexyl~ Representati~e substituted-phe~yl 9 ~2 qroups are 2-chlorophenyl, 2,4-dichl~rophenyl~ 4-methylphenyl and ~,3-dim~thylphenyl.
11 Repr~ssnt~tive h~alovinyl gro~lps which Rl ~ay represent 12 are 2^chlorori~yl, 2,2-dibromovlnyl and trichiorovinyl.
13 ~ P(epresenta~ive N-R groups are amino; alkylaminD s~ch as 14 . methyla~ino, ethylamino, isopropylamino~ n-he~ylamt no~ etc.;
alkenylamin~ ~such as :allylami~o~ 3-buteny:lamino, etc.; and 16 arylamino su~h ~s phenylamino, 4-chlorophenyla~ino and 4-17 tolyla~ino. ~ : -18 ~ Preferably Ar is phenyl ~substituted ~fith 1 to 2 of th~
19 ~ same ~or different subs~ituents selected from fluoro, chloro, bromo or ~alkyl of 1 ~to 2 carbon atoms, ~r 2-alkyl-1-naphthylO
21 ~he most preferr~d ar groups are 2,6~dimethylphenyl or 2-me~hyl-22 1-naphthyl.
23 ~ Preerably :R~ ::is~alkoxymethyl of 1 to ~ carbon atoms, 24 chlorom~thyl or~ brpIomethyl~ Most pref~rably ~ lS methoxymethyl or chloromethyl.
26 Pr~ferably R2 is hydrogen or me~hyl.
27 Preferably R is alkyl of 1 to 6 carbon atoms"
28 especially methyl. ~ :
29 ~he N-phenylamino-~and ~-substituted phenylamino-thiolac:tones of th~ in~rention may be represented by the formula : ;
8 Moser, and U,.~S. Patent No. 4,015,648, i sued May 24, 1977 to H.
9 Moser, disclose the use of N- (methoxycarbonylethyl) -N haloa~ etyl-anilines zs preventive and curative fungicides.
11 German Patent Publica~ion Nos. 29643,403 and 2,643,44S, 12 puhlished April 7r 1977~ disclose the use of ~I~(alkylthio-13 carbonylethyl)acetani1ldes for controlling funyi, particularly 14 those of the class P_ycomycete~
Netherlanas Patent Publicatio~ ~lo. 152, 849, published 16 .april~ 15, 197~7, discloses ~the; use of N-lal3soYymethyl~ acetaniliaes -~ 17 as fungicides.
18 ~ ~ F~ Jo Sch~inn, T. Staub and PO Vrech, 29 Inter~at.
19 symposium Uber Pflanze~schutz,t Gent., ~1977 ~Bisannu~l German Crop Protection ~eeting, 1977), disclose N-~2~6-di~ethylphenyl)-N-(2'-21 methoxyacetyl)-alanine methyl ester for the control of -22 Ph~oE!hthor- afestgns, P1asDoPara vit__ola and Pseudo~erono~o~a 23 humili.
24 SUM~APsY OF TH~ INVEN~ION
--_ __ _ It has n~: been fouDd that 3- (N-acyl-N-arylamino~ -76 gamma-butyrolacton2s, butyr~thiolactones and butyrolactams are 27 effective for the control of fungi, e~p~cially for downy milde~ '.
28 fu~gal infection caused by fungal species of th~e Peronos~o_ac~eae .
29 fa~ily and late blight fungal infection caused by PhYto~t~ora 30 ~gfestan~. ~So e of the co~pounds of tha inrention are effective 31 both as prot~ctant fungicides, i.e., they preYent or pr~tect ~ 33~3S ~
.
against fungal infections, and as eradicant fungicides, i. e ., they eliminate and cuEe established infections. The compounds ~.
of the invention are especially preferred for the control of grape downy mildew. .
DESCRI~r~N ~~ T11r ~N~rNlIoN
The compounds of the present invention are within the following hroad classes of compound represented by the Formula (I) : :
O : , : C Rl :
Ar-N \ (I) CH CH . :
Q=C l 5CH-R2 .:
\y/ ;:
wherein Ar is phenyl, naphthyl, or phenyl or naphthyl sub-stituted with l to 4 of the same or different substituents :
selected from fluoro, chloro, bromo, alkyl of l to 4 carbon atoms or alkoxy of l to 4 carbon atoms; Rl is alkyl of l to 6 carbon atoms, hydroxymethyl, halomethyl of l to 3 of the same or different halogens selected from fluoro, chloro or bromo, alkan-oyloxymethyl of l to 6 carbon atoms, alkoxymethyl of l to 6 car- ;
bon atoms, alkylthiomethyl of l to 6 carbon atoms, phenylthio-. .
methyl, phenoxymethyl, phenylthiomethyl or phenoxymethyl sub- ;~ :
stituted on the phenyl ring with l to 2 of the same or : different substituents selected from fluoro, chloro, bromo, alkyl ;~
of l to 4 carbon atoms or alkoxy of l to 4 carbon atoms, phenyl, phenyl substituted with l to 4 of the same or differen~ sub-stituents selected from fluoro, chloro, bromo, alkyl of l to 4 ~ ~:
carbon atoms or alkoxy of l to 4 carbon atoms, halovinyl of l to ~ ~:
~.,, ~ ~ ~ 3 ::
3 of the same or different halogens selected from fluoro, chloro :
or bromo; and R is hydrogen, chloro, bromo, alkyl of 1 to 6 carbon atoms, phenyl or phenyl substituted with 1 to 2 of the same or different substituents selected from fluoro, chloro, bromo or alkyl of 1 to 6 carbon atoms; and Y is O/ S or N-R
wherein R is hydrogen, alkyl of 1 to 6 carbon atoms, alkenyl of 3 to 6 carbon atoms, phenyl, phenyl substituted with 1 to 4 of the same or different substituents selected from fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon ~:
atoms, with the proviso that when Ar is phenyl or substituted phenyl as described above and Rl is alkyl, halomethyl, phenyl, halovinyl or substituted phenyl as described above, then Y is not :: ~
o or NR. ^:
In particular, the present invention provides a method or the control of fungi which comprises contacting said :
fungi or their habitats with a fungicidally effective amount of a compound of the formula :
~1 ' C_Rl Ar-N (I~
7 f 2 ~
O-C OEI-R ::
\0/
wherein Ar is phenyl, naphthyl, or phenyl or naphthyl substituted with 1 to 4 of the same or different substituents selected f~om ` ;~
fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms; Rl is alkyl of 1 to 6 carbon atoms, alkan- ;~
~ .
- 4 - :
3~
oyloxymethyl of 1 to 6 carbon atoms, phenyl, phenyl substituted with 1 to 4 of the same or different substituents selected from fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms, halovinyl of 1 to 3 of the same or different halogens selected ~rom fluoro, chloro or bromo; and R is hydrogen, chloro, bromo, alkyl of 1 to 6 carbon atoms, ~ r phenyl or phenyl substituted with 1 to 2 of the same or different substituents selected from fluoro, chloro, bromo and alkyl of 1 to 6 carbon atoms.
10Preferably, Ar is phenyl or substituted phenyl, or ~;
naphthyl or substituted naphthyl.
Furthermore and preferably R is chloromethyl or alkoxy-methyl and R is methyl.
The above de ined compounds of Formula (IV) are particularly useful for controlling the growth of Phytophthora infestans and Plasmopara viticola.
Representative substituted-phenyl groups which Ar, R
or Rl may represent are 2-fluorophenyl, 2,4-dichlorophenyl, 3,5-dibromophenyl, 4-methylphenyl, 2,6-diethylphenyl, 4-methoxy-~0phenyl, 2,6~dimethyl-4-chlorophenyl, 2,3,6-trimethylphenyl, 2,3,5,6-tetramethylphenyl. Preferred substituted-phenyl Ar groups are phenyl substituted with 1 to 2 of the same or different substituents selected from chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms. Most preferred substituted-phenyl Ar groups are 2,6-dialkylphenyl, especially 2,6-dimethylphenyl.
Representative substituted-naphthyl Ar groups are 1-naphthyl, 2-naphthyl, 1-methyl-2-naphthyl, 4-methyl-2-naphthyl, 4-methyl-1-naphthyl, 2-chloro-1-naphthyl, 2-methoxy~l-naphthyl, 2,4-dimethyl-1-naphthyl and 2~7-dimethyl-1-naphthyl. Preferred ~,,., , ~.
~ . ,.. ,.. , _ ~ .
- 4a -~ `33~
substituted naphthyl A.r groups are 2-alkyl~l~naphthyl groups, ;
especially 2-methyl~l-naphthyl.
Representative halomethyl groups which Rl may repre-; sent include fluoromethyl, chloromethyl, bromomethyl, dichloro-methyl, tribromomethyl and fluorodichloromethyl. The preferred halomethyl Rl group is chloromethyl.
- Representative alkanoylmethyl R groups are acetyl-, methyl, propionylmethyl and hexanoylmethyl.
Representative alkoxymethyl Rl groups are methoxy~
, ` 10 methyl, ethoxymethyll isopropoxymethyl and n-pentoxymethyl.
The preferred alkoxymethyl RL group is methoxymethyl.
~, ;': -' ` ~:, ~;''"' - - 4b - ~i ;
53~;9 1 Representative alkylthiomethyl Rl qroups are ~ethyl-2 thiomethyl, n-propylthiomethyl and n-pe~tyl~hio~ethyl. .
3 Representati~e substitutQd-ph~nylthio~ethyl a~d : 4 substituted-phenoxy~ethyl Rl groups are 4-chlorophenylthiomethylv S 4~methylpheno~ymethyl, 2,4~dichloropheno~y~ethyl, 3,5-dime~hyl-6 phenylthiomethyl and 2-chloro-4-methylphe~oxymethyl1 7 Repre~entati~e alkyl R, R~ ana R2 gr~ups are methyl, 8 e~hylp isopropyl ana n-hexyl~ Representati~e substituted-phe~yl 9 ~2 qroups are 2-chlorophenyl, 2,4-dichl~rophenyl~ 4-methylphenyl and ~,3-dim~thylphenyl.
11 Repr~ssnt~tive h~alovinyl gro~lps which Rl ~ay represent 12 are 2^chlorori~yl, 2,2-dibromovlnyl and trichiorovinyl.
13 ~ P(epresenta~ive N-R groups are amino; alkylaminD s~ch as 14 . methyla~ino, ethylamino, isopropylamino~ n-he~ylamt no~ etc.;
alkenylamin~ ~such as :allylami~o~ 3-buteny:lamino, etc.; and 16 arylamino su~h ~s phenylamino, 4-chlorophenyla~ino and 4-17 tolyla~ino. ~ : -18 ~ Preferably Ar is phenyl ~substituted ~fith 1 to 2 of th~
19 ~ same ~or different subs~ituents selected from fluoro, chloro, bromo or ~alkyl of 1 ~to 2 carbon atoms, ~r 2-alkyl-1-naphthylO
21 ~he most preferr~d ar groups are 2,6~dimethylphenyl or 2-me~hyl-22 1-naphthyl.
23 ~ Preerably :R~ ::is~alkoxymethyl of 1 to ~ carbon atoms, 24 chlorom~thyl or~ brpIomethyl~ Most pref~rably ~ lS methoxymethyl or chloromethyl.
26 Pr~ferably R2 is hydrogen or me~hyl.
27 Preferably R is alkyl of 1 to 6 carbon atoms"
28 especially methyl. ~ :
29 ~he N-phenylamino-~and ~-substituted phenylamino-thiolac:tones of th~ in~rention may be represented by the formula : ;
- 5 -.~ 33~
~ C-R l Ar- ~
: C~ CH2 (II) ,r! . l l ,, O=C~; CH~ R2 1 wherei~ Ar is phenyl or substltuted phenyl as preYiously deine~
2 and Rl and R2 have the same significance as previously defi~ed.
3 In formula (Il)~ Ar preferably is phenyl substi~u~ea with 1 ~o 2 4 of the same or different substit:uents selected from fluoro, chloro, bromo~ alkyl of 1 to 4 carbon atoms ~r alkoxy of 1 to 4
~ C-R l Ar- ~
: C~ CH2 (II) ,r! . l l ,, O=C~; CH~ R2 1 wherei~ Ar is phenyl or substltuted phenyl as preYiously deine~
2 and Rl and R2 have the same significance as previously defi~ed.
3 In formula (Il)~ Ar preferably is phenyl substi~u~ea with 1 ~o 2 4 of the same or different substit:uents selected from fluoro, chloro, bromo~ alkyl of 1 to 4 carbon atoms ~r alkoxy of 1 to 4
6 car~on atoms~ A preferred class of N-pbenyla~ino- and N-~, 7 substituted phenyl~m inothiolactones is that represented by the 8 formula O
b-RI (III) R~S;~ ~ O=C IH_R2 s .~ ...... .... . . .
: 9 :~herein Rl~is chl~or~methyl, bromomethyl or. a:l~o~ymethyl of 1 to 4 1 O carbon ato~s~ RZ ~is hydr~gen or methyl, and R~ a~d Rs 11 individua::Lly are methyl or ethyl. Particularly preferred 12 compounds of formula: (~II) are those wh~rein Rl is -hl~romethyl 13 or methoxymethyl, R2 is hydrogen and ~ and Rs are methyl.
14 ~ ~he~ N-pheDylami~o, nd N-su~stituted-phenylaminolactoDes .
: 15 of the inveDtio~ ~ay be represented by the formula O
C-R
Ar- ~
\ (IV) CH _--~CH2 O~C~ ~CH-R2 '' . ...
, _ , ~33~
, ~herein Ar is phenyl or substituted phe~lyl a~ previousl~ definea, 2 and R~ and R2 have the same significance as pre~iously defined.
3 A preferred c}ass of N-phenylamino- and N-substituted-4 phenylamin~lactones is that repre en~ed by the formula R4 C~
\ (V
CH--fH2 \O~
~ wherein Rl is chlorDmethyl, bromomethyl or alkoxymethyl ~ 1 to 4 6 carbon ato~s, R2 is hydrogen or methyl, and R~ and ~5 indi-
b-RI (III) R~S;~ ~ O=C IH_R2 s .~ ...... .... . . .
: 9 :~herein Rl~is chl~or~methyl, bromomethyl or. a:l~o~ymethyl of 1 to 4 1 O carbon ato~s~ RZ ~is hydr~gen or methyl, and R~ a~d Rs 11 individua::Lly are methyl or ethyl. Particularly preferred 12 compounds of formula: (~II) are those wh~rein Rl is -hl~romethyl 13 or methoxymethyl, R2 is hydrogen and ~ and Rs are methyl.
14 ~ ~he~ N-pheDylami~o, nd N-su~stituted-phenylaminolactoDes .
: 15 of the inveDtio~ ~ay be represented by the formula O
C-R
Ar- ~
\ (IV) CH _--~CH2 O~C~ ~CH-R2 '' . ...
, _ , ~33~
, ~herein Ar is phenyl or substituted phe~lyl a~ previousl~ definea, 2 and R~ and R2 have the same significance as pre~iously defined.
3 A preferred c}ass of N-phenylamino- and N-substituted-4 phenylamin~lactones is that repre en~ed by the formula R4 C~
\ (V
CH--fH2 \O~
~ wherein Rl is chlorDmethyl, bromomethyl or alkoxymethyl ~ 1 to 4 6 carbon ato~s, R2 is hydrogen or methyl, and R~ and ~5 indi-
7 v~aually are methyl or ethyl. Preferred compounds ~f formula (Y) : 8 ~re those wherein X~ is chloromethyl or methoxymethyl, R2 is 9 hydrogen~ and R" ana R5 are methyl.
The ~-naphthyla~mino- and ~;-substituted naphthylamino-11 lactones and thiolactones o~ the invention may be represe~ted by 12 the formula ~C- R
Ar-N\ I (VI ) f H--f H 2 O-C~ ~CH-R2 ' Y
13 ~herein Ar is naphthyl or substituted n~ phthyl, and wherein Rl, 14 RZ and Y ha~e the s~e significance as previously defined. A
. 15 preferred class of N-~aphthyl a~d N-naphthyl-substitute~-amino-16 lac'ones and thiol~eton~s is that. represented by th~ for~ula ~C-RI (VII) \,=/ O=C~CH-1~2 .. . _ . . ..
~33~;
, .
t wherein R~ is _hloromethyl, bromomechyl or alkoxymethyl of 1 t~ 4' 2 carbon atoms; R 3 is hydrogen or alkyl of 1 to 3 carb~n ~toms; a~d 3 Y is oxygen or sulfur. Particularly preferred compounds of 4 formula ~yIr~ are thos~ ~erein R' is chloromethyl or m2thoxy-5 methyl, R3 is ~sthyl and Y is oxygen.
6 P~epresenta~ive compoullds of f~rmula ~I) inclule:
7 3- ~ N- bromoacetyl-N-phenylamino~ -ga~ m a-b ut yrothiola-tone 3- (N~ sopropoxyacetyl-N -4-chlo-ophenylamino~ -gamma-9 butyrothiolacton~
3-(N-phenoxyace~yl-N-4-m~thoxyphenylamino~-gam~a-1 1 b ut~r ot h iola ct~n e 12 3-(N-chloroacetyl-N-2,6-dimethylph~nylamino)-S-methyl-gamm~-1 3 butyrothiolactone 14 3-(N-dichloroacetyl-N-2~6-dimethylphe ~la~iao~-gam~a-butyrothiol~ton~
~6 3-~N-hydroxya~etyl-N-3,~-dimethylphenylamino)-~amm~-17 butyrothi~lactone 18 3-(N-chlor~acetyl-N-4-methylphenyl~mino)-5~chl~ro-~a~ma-19 butyrothiolactone 3-(N-hydroxyzcetyl~N-2-methoxyphenylami~o~-gamma-21 . butyrolactone 22 3-~N-chloroa~etyl-N-2~methylnaphth-1-yla~ino)-S-ph2~yl-23 gamma-butyrothiolactone 24 3-(N-~thoxya_etyl-N-2-methylnaphth-1-ylamino)-gam~a-bu~yrothiolac~one 26 3-(N-chlQroacetyl-~ naphthylamin~)-5-methyl-gamma 27 ~utrrothiolacto~s 28 3-~N-hydroxyacetyl-N-2-met~ylnaphth-1-ylamin~)-ga~ma-29 butyrolactone 3-~N~a~et~xya~etyl-N-2-methylnaphth-1-ylamino~-gamma-31 b~yrolactone 32 3-f~-acetyl-N-phenylami~o)-~amma-butyrolactone 33 3-~N-propionyl-~-4-chlorophenyla~ino)-gam~a-butyr~lactone 34 3-~N-fluoroacetyl-N-2,6-dim~thylph~nylamino)-gamma-butyrolactone 36 3 (N-3-chloropropionyl-N-3~4-dibro~ophenylamin~)-gqmma-37 butyr 012 ctone 38 3-(N-4-chlorobenzoyl-N-2-methox~phenylami~o) gamm~-39 ~utyrolactone 3 (N-~,4-di~ethylbenzoyl-N-2-fluorophenylamino)-ga~ma-41 b~t~rolactone 42 3-(N-4-methoxybenzoyl-N-4-m~thoxyphe ny} amino) -g amma-43 ~tyrolactone 44 3-~N-acetoxyac~tyl-N-?,6-dimethylphenylami~ol-5-methyl-4S gamma-butyrolactone 46 3-tN-be~z~yl-N-2,6-diethylphenylamino)-5 chlor~-gamma-47 butyrolactone 48 3-(N-chloroacetyl-N-3v4-dichloroph2nylami~o)-5-hexyl~gamma-49 butyrolactone 3-(N-a_etyl-N-2,6-dim thylphenylamino)-gamma-buty.~lactam 5 1 3- (~-GhlOrOaCetyl-2~ 6-di~ethoxyphenylamino) -gamma-52 butyrolacta~ .
53 3-~N-benzoyl-N-2-nitrophenylamino~-gamma-butyr~lactam 54 1-~ethyl-3-~N-chloroacetyl-N-2, 6-dimetnylphenylamino) -gamm~ -butyrolactam 3~
1 1-allyl 3-(N-p-chlorobenzoyl-~-2~6-dimethylpheny~ o)-2 qamma-but~rolactam, and 3 3-[N-bro~Dacetyl-N-phenyla~ino3-1,5-dimethyl-gamm~-4 butyrolactam.
The lastone and thiolactone c3mpounds of the inventio~
6 may be preparea by alkylating an anilin~ lVIII~ h a~ alpha-7 halo-~a~ma-butyrolactone or alpha-halo-gamma-butyrothiolactone
The ~-naphthyla~mino- and ~;-substituted naphthylamino-11 lactones and thiolactones o~ the invention may be represe~ted by 12 the formula ~C- R
Ar-N\ I (VI ) f H--f H 2 O-C~ ~CH-R2 ' Y
13 ~herein Ar is naphthyl or substituted n~ phthyl, and wherein Rl, 14 RZ and Y ha~e the s~e significance as previously defined. A
. 15 preferred class of N-~aphthyl a~d N-naphthyl-substitute~-amino-16 lac'ones and thiol~eton~s is that. represented by th~ for~ula ~C-RI (VII) \,=/ O=C~CH-1~2 .. . _ . . ..
~33~;
, .
t wherein R~ is _hloromethyl, bromomechyl or alkoxymethyl of 1 t~ 4' 2 carbon atoms; R 3 is hydrogen or alkyl of 1 to 3 carb~n ~toms; a~d 3 Y is oxygen or sulfur. Particularly preferred compounds of 4 formula ~yIr~ are thos~ ~erein R' is chloromethyl or m2thoxy-5 methyl, R3 is ~sthyl and Y is oxygen.
6 P~epresenta~ive compoullds of f~rmula ~I) inclule:
7 3- ~ N- bromoacetyl-N-phenylamino~ -ga~ m a-b ut yrothiola-tone 3- (N~ sopropoxyacetyl-N -4-chlo-ophenylamino~ -gamma-9 butyrothiolacton~
3-(N-phenoxyace~yl-N-4-m~thoxyphenylamino~-gam~a-1 1 b ut~r ot h iola ct~n e 12 3-(N-chloroacetyl-N-2,6-dimethylph~nylamino)-S-methyl-gamm~-1 3 butyrothiolactone 14 3-(N-dichloroacetyl-N-2~6-dimethylphe ~la~iao~-gam~a-butyrothiol~ton~
~6 3-~N-hydroxya~etyl-N-3,~-dimethylphenylamino)-~amm~-17 butyrothi~lactone 18 3-(N-chlor~acetyl-N-4-methylphenyl~mino)-5~chl~ro-~a~ma-19 butyrothiolactone 3-(N-hydroxyzcetyl~N-2-methoxyphenylami~o~-gamma-21 . butyrolactone 22 3-~N-chloroa~etyl-N-2~methylnaphth-1-yla~ino)-S-ph2~yl-23 gamma-butyrothiolactone 24 3-(N-~thoxya_etyl-N-2-methylnaphth-1-ylamino)-gam~a-bu~yrothiolac~one 26 3-(N-chlQroacetyl-~ naphthylamin~)-5-methyl-gamma 27 ~utrrothiolacto~s 28 3-~N-hydroxyacetyl-N-2-met~ylnaphth-1-ylamin~)-ga~ma-29 butyrolactone 3-~N~a~et~xya~etyl-N-2-methylnaphth-1-ylamino~-gamma-31 b~yrolactone 32 3-f~-acetyl-N-phenylami~o)-~amma-butyrolactone 33 3-~N-propionyl-~-4-chlorophenyla~ino)-gam~a-butyr~lactone 34 3-~N-fluoroacetyl-N-2,6-dim~thylph~nylamino)-gamma-butyrolactone 36 3 (N-3-chloropropionyl-N-3~4-dibro~ophenylamin~)-gqmma-37 butyr 012 ctone 38 3-(N-4-chlorobenzoyl-N-2-methox~phenylami~o) gamm~-39 ~utyrolactone 3 (N-~,4-di~ethylbenzoyl-N-2-fluorophenylamino)-ga~ma-41 b~t~rolactone 42 3-(N-4-methoxybenzoyl-N-4-m~thoxyphe ny} amino) -g amma-43 ~tyrolactone 44 3-~N-acetoxyac~tyl-N-?,6-dimethylphenylami~ol-5-methyl-4S gamma-butyrolactone 46 3-tN-be~z~yl-N-2,6-diethylphenylamino)-5 chlor~-gamma-47 butyrolactone 48 3-(N-chloroacetyl-N-3v4-dichloroph2nylami~o)-5-hexyl~gamma-49 butyrolactone 3-(N-a_etyl-N-2,6-dim thylphenylamino)-gamma-buty.~lactam 5 1 3- (~-GhlOrOaCetyl-2~ 6-di~ethoxyphenylamino) -gamma-52 butyrolacta~ .
53 3-~N-benzoyl-N-2-nitrophenylamino~-gamma-butyr~lactam 54 1-~ethyl-3-~N-chloroacetyl-N-2, 6-dimetnylphenylamino) -gamm~ -butyrolactam 3~
1 1-allyl 3-(N-p-chlorobenzoyl-~-2~6-dimethylpheny~ o)-2 qamma-but~rolactam, and 3 3-[N-bro~Dacetyl-N-phenyla~ino3-1,5-dimethyl-gamm~-4 butyrolactam.
The lastone and thiolactone c3mpounds of the inventio~
6 may be preparea by alkylating an anilin~ lVIII~ h a~ alpha-7 halo-~a~ma-butyrolactone or alpha-halo-gamma-butyrothiolactone
8 tIX) and subsequently acylating the alpha-(N-arylamino)-gamma
9 butyrolactone or butyrothiolactone ~X) with an acyl halide(XI) to
10 gi~e the 3-tN-acyl-N-arylamino)-gam~a-butyrolactone or bùtyro-
11 thiolactone produc~ , as depicted by the follo~ g e~uations:
ArN~2 ~ X-CH l~2 base Ar-NH-CH lH2 (l) o=C\ / CH-R2 -HX O=C \ / CH-R2 . Y . Y
(IX) ~ (X?
Ar-NH-C~ - C~I2 ,.
+ X--C-R l ' C-R l O=C\ / H-R2 (XI) -~IX Ar-N \ ~2) C~ - CH~
(X) O=C~ ~CH--R2 (I )
ArN~2 ~ X-CH l~2 base Ar-NH-CH lH2 (l) o=C\ / CH-R2 -HX O=C \ / CH-R2 . Y . Y
(IX) ~ (X?
Ar-NH-C~ - C~I2 ,.
+ X--C-R l ' C-R l O=C\ / H-R2 (XI) -~IX Ar-N \ ~2) C~ - CH~
(X) O=C~ ~CH--R2 (I )
12 wherei~ Ar, Rl and R Z have the same significance as preYiously
13 defined, X is chloro or bromo, and Y is O or S.
14 The alkylation reaction ~1) is conducted in the
15 presence of a base. Suitable bases are inorga~ic alkali metal
16 carbonates such as s odium carbonates or potassi~lm carb~nate or
17 organic amines such as trialkylamines, a.g., triethylami~e, or
18 Pyridine compounds, e.g~, pyridine or 2,6-dimethylpyridine.
19 Generally, substantially equimolar amounts of reacta~ts ~III) and ~ nd the base are employed. In one modification of the 21 reac~ion9 a molar e~cess o~ the aniline reactant ~YIII) is used 22 as the base, a~d n~ additional base is employed. rhe reac~io~ i~
~ . .
_ g _ 3~3~
conducted in inert organic solvents, e. g., apolar dipr~tic 2 sol~ents su~h as dim ethylormamide ~nd ~cetonitrile and aro~atic .
3 hydrocarbons s~ch as benzene and toluene, at reactio~ tampera-4 tures Yaryi~lg from 25C to 150C, preferably from soor to 150C. .
Water may be employed as a co solvent. The reac~io~ pressure ~y 6 be a~mospheric, subatmospheric or super~tmospheric. Ho~/ever~ ~r 7 convenience of conducting the rea::tion, the pressure is generally 8 atmospheric. The reaction time will, o~ course, vary depending 9 upon the reactants and the reaction temperature. Ginerally the reaction time is fro~ 0.25 to 24 hours. The product ~X~ is 11 generally purified by conventional procedures, e. g., extraction, 1~ distlllation~ or crystallization, ~efore use in the ac~l~tion 13 reaction (2).
14 Preferred alkylation reaction conditions are given in more detail in the commonly assignea U.SO applicati~n Serial ~o.
16 847,503 of Richard ~. Reynolds, Jr., entltled "Alkyla~ion of :17 Aniline ~i~h a~Lactone in ~he Presence;~f Water", filea o~
18 ~o~ember 1, 1477.
19 : The acylation:reaction (2) is conducted by conventional procedures. The relctants ~X3 and (XI~ are generally contacted 21 in substantially equimolar amounts in an inert orga~ic sol~e~t ~t 22 a temperatura of 0 ~o 100C. Suitable inert organic s~lvents 23 include ethyl a~etate, methylene dichloride, dimethox:yethane, 24 ben~ene, ~t~. The product is isola~ed a~d p~rified by conven-tional procedures such as extraction, distillation~ chr~ma-26 toqraphy, crystalli~ation, etc.
27 Whon pr~paring a butyrolactone product (c3mpou~ds of 28 ~ormula (I) ~herein Y=O3, an orga~ic amina such as a trialkyl-29 a~ine or a pyridine compound may ~e employed as an acid acceptvr.
However, ~hen preparing a but~rothiolac~one proauc~ ~compounds of 31 Pormula (I~ ~herein Y=S~, an organic amine should not ba 32 ~ employed.
~33~
Preferred acylation reaction conditions are given in more detail in the commonly assigned United S-tates Paten-t No.
4,224,453 of Richard N. Reynolds, Jr., Stephen D. Ziman and David C. K. Chan, entitled 'IAcylation of Lactone-Substituted Aniline Compound in the Absence of an Acid ~cceptor", issued on September 23, 1980.
The compounds of Formula (I) wherein Rl is alkylthio-methyl, phenylthiomethyl or substituted-phenylthiomethyl may be prepared from the corresponding compound wherein Rl is halo-methyl by reacting the corresponding halomethyl compound with an alkali metal mercaptide by conventional procedures as depicted ~ ;
in the following equation (3)~
O ~ o ~ :
ll ll Ar-N \ + RSM ~ Ar-N \ + MX (3) I 1 2 1 1 2 ~ -O=C CH-R O=C CH-R
\Y/ ' \y/ : ~
,~ .
wAerein Ar, R , X and Y are as previously defined, M is alkali metal, R7 lS alkyly~ phenyl or substituted phenyl moiety of Rl.
In reaction (3), Y preferably is oxygen.
The compounds of Formula (I) wherein Rl is hydroxy~
methyl and Y is oxygen may be prepared by treatment of the cor-responding compound wherein R is halomethyl with an inorganic alkali metal hydroxide such as aqueous sodium hydroxide. The compounds of Formula (I) wherein Rl is hydroxymethyl and Y is oxygen or sulfur may be prepared by hydrolysis of the corres-ponding compound wherein Rl is alkanoyloxymethyl ~e.g., acetoxymethyl).
The compounds of Pormula (I) wherein R is chloro or bromo are generally prepared by chlorinating or brominating -the `,: ' F'~, ` - - 1 1 -3i,, 3~
3~
1 correspondinq compound vherein R2 is hyarogen with a chlorinating 2 or brominatinq agent such as ~-bromosuc~inimide or N-chlorosuc-3 cinimide by conv~ntional procedures, as depicted in the following 4 equation l4~:
O O O O
,. .. .. ..
C - R 1 C - CH 2 C - R 1 ~C - C ~ 2 Ar-N\ + X-N~ ¦ ) Ar-N\ + HN~
CH lH2 C-CH2 CH--l}12 C--CH2 O=C~ ~CH 2 O=C~ ~CH-X
Y `Y (4) . .
5 wherein Ar, Rl, Y and X are as previously defined.
6 The lactam compounds of the invention ~ay be preparea 7 by cyclizinq a gamma-halo amide (XII) in the presence of a base 8 and subseque~tly acylating the gamma-la~tam (XIII) to gLYe the 3-9 (N-acyl-N-arylamino~-gamma lactam produ_t (~), as depicted in the following equations:
base ~r NH-CH-CH2-CHR2 ~ Rr-NH-CR~ 2 ~HX l l : O=C Br O=C.\ /CHR2 H~IR ~ N (5) (XII) i R
5XIII) o ba5e C-R
~r-NH-CH;- CH2 + X-C-Rl ~ Ar-N
O--C~ ,1HR2 ~HX \CH--I H2 N ~=~\ C_R2 : R N (6) R
~XIII) (I), YsNR
11 ~herein Ar~ R~ Rl, RZ and X ha~e the same significance ~s 12 prev~ously definedO
13 The cyclization reaction (5) is conducted by ~r~ating 14 the gamma-halo (~ ith substantially equimolar z~ou~ts of strong inorganic base, e.g.~ alkali met~l alko~ides such as ;3 3~
sodium me~hoxide, p~tassium ethoxide, etc. O and alkali metal 2 hydrides such as sodium hydride~ ~hen ~n al~ali metal ~lko~ide 3 base is employed, the reaction is preferably conducted in an 4 alkanol solvsnt su~h as methanol and ethanol. Hhsn a~ alkali metal hydriae base is employed, the reaction is preferably 6 conducted i~ a polar non-hydric oxyge~ated sol~e~t such as 7 dimethoxyet.hana. ~he lactam product (XIII) is purified by 8 convantional prosedures such as ext~action, distillatio~ chrom~-9 to~raphy or crystallization before use in the ac~ylation reaction .
~6).
11 The acylation reaction (6) is conducted in the presence 12 o~ an orqanic amine base by the same procedure disclosed above 13 for reaction (2).
14 The gamm -halo ~eactant (XII) is suitably prepared by 15 halogenating by con~entional procedures, e.g.~ ~lth phosphorus 16 tribromide or thionyl chloride, the corresponding gamma-hydroxy, 17 :i.e., ~he co~pound o:f formula (XIV):
18 ~ Ar-NH-CH-CH~-CElRZ (XIVj 19 . . I
O=C OH
23 The ga~ma-hydro~y fXIV) in turn is prepared by reacting 24 the 3-N-arylamino)-3amma-lactone ~X) with ammonia or an amine 2~ tH2~R) in an inert solvent at a temperature of ~5~ to 100C~ an~
2~ subsequently purifying th~e product by c~nventional pro~ures.
27 UTILIqlY
28 The co~pou~ds of ~he inYention are useful for 29 controllinq ungi, par~icularly plan~ fungal infec~ionsO
~owever, some fungicidal compositions of the invention may be 31 more fungicidally active than others ag~i~st partic~lar fungi.
32 For example, the activity of the preferred co~pounds of the 33 inYenti~n is highly specific for certain fungal diseases such as^
~33~
1 downy milde~s, e.g., PlasmoPara Yit~CQla ~grapes~ and PQEono~oEa 2 Darasitic3 (cabbage and collard), late blights" e.g., 3 PhvtoPhthQEa infestans (tomatoes and potatoes)~ and cro~n and 4 root rots, e.g., PhYto~hthorL-S The ~ompounds of the in~entio~ are particularly useful 6 funqicides because they cure establishe~ fungal inf~cti~ns. This 7 per~its aconomical use of the fungicides of the invention, 8 because ~hey need n~t be applied to plants unless fungal 9 infection actually occurs. q~huso a preventative progr~ of applying fungicides against potential ungal infectio~ is not 1 1 necessary.
12 Uhen used as fungicides, the ~ompounas of the in~enti~n 13 are applied in fungicidally effective amounts to fungi and~or 14 their habitats, su~h as vegetative ~osts and nonvegetative hosts, e.g., animal products. The amount used ~ill, of course, depend 16 ~ on several factors such as the host, the type of fungus a~d the 17 particular compoun~ of the in~ention. As with most pesticidal 18 co~pou~ds,: thç fu~ngicides o~ the inve~tion are not usually 19 applied ~ull strength, bu,t are generally incorporated irith conventiollal, biolsgically inert extenders or carriers normally 21 employed f~r facilitating dispersion of active fungicia 22 compounds, recognizing tha~ the formulation a~a ~ode of 23 applicatlon may affect the activity of the ~ungicide. Thus, the 24 fungicides of the inventio~ may be formulated and applied as granules, as poYdery dusts, as wettable powders, as emulsifiable -26 concentrates, as solutions, or as any of several other known 27 types of formulations, dependiny on the desired mode of 28 application.
29 ~ettable po~ders are in the form of finely di~ided particles which dispers readily in water or other dispersant.
31 These compositions normally contain fro~ about 5-BOS fungicide, .
, .
33~
1 and the rest inert material, which ~ncludes dispersing ~gen~s, 2 emulsilying agents ~nd wetting ag~nts. The powder ma~ ~e applied 3 to Ihe 60il as a dry dust, or preferably as a suspension in 4 ~ater. T~pical carriers i~clude fuller~s earth, ka~lia clays, silicas, an~ other highly absorbent, slettable, inorgani~
~iluents. rrpical wetting, ~ispersing ~r e~uls~fyirlg ~gents 7 include, ~or examPle: the aryl and alkylaryl sul~onates and 8 their so~ium s~lts, lkylamide sulfonat~s9 includin~ f~tty methyl 9 taurides; alkylaryl polyether alcohols, sulfated hiqher alcohois and polyvinyl ~lcoh~ls; polyethylene oxiaes, sulfonatea animal 11 and ~eq~table ~ils sulfonated pstroleu~ oils, fatty a~id asters 12 of polyh~aric alcoh~ls and the ethylene oxide addition products 13 OI such es~ers; and the addition products of long-chain 14 merc:aptans and ethylcne oxide. Many other typ~s of useful surface-acti~e ageDts are avallable in ~ommerce., The surrace-16 active aqent, whe~ used, normally comprises from 1~ to 15~ by 17 ~eight of the funqicidal co~position.
18 Dusts are freely~flow1n~ admixtures of tha a~tive 19 ; funqi~ide ~ith fi~nely di~ided solids su_h as~t~lc, natural clays, kieselguhr, pyrophyllite, chalk, diatom~ceous earths, c~lciu~
21 phosphates, calcium and magnesium carbonates, sulfur, lime, 22 flours, and other orqanic and inorganic solids whi~h a~t as 23 dispersants and ~ar-rlers for ~he toxicant~ These finely divide~
24 solias have an average part~cle size of less than about S0 microns. ~ typical dust for~ulation useful herein co~tains 75%
26 silic~ a~d 25~ ~f the toxicant.
27 Useful liquid c~ncentrates include the emulsifiable 28 concentrates, ~hich are ho~ogeneous liguid or paste compositions 29 ~hich are readlly aispersed in water or o~her dispersant~ a~d m~y consist en~irel~ of the fungicide wi~h l liquid or solid 31 emulsifying aqent, or may also contain ~ liquid ~arrier such as 3~;~
xylene, heaYy aromat ic naphthast~ isophorone, and other 2 nonvolatile organic solvents. For appli~atioi, these.
3 concentrates are dispersed in water or other liquid carrier, ana 4 sre r,ormally applied as t spray to the ~rea to be treated.
~ther useful formulations for fungicidal 2pplications 6 include simple solutions of the active fungicide ~n a dispersant 7 in which it is completely soluble at the desired concentration, 8 such as acet~n~ ~ alkylated naphthalenes~, xylene, or oth~r organi ~ -9 solvents. Granular formulatio~s, ~herein the fungicide is carried on rela'iYely coarse particles, are of particular utility 11 for aerial aistri~utiorl or for penetration of aover-crop canopy~
12 ~ressurizea sprays, typically aerosols wherein the active 13 ingredient is dispersed in finely dividad form as a result of 14 vaporizatio~ of a lo~boiling dispersant solvent carrier, su~h as the Freons, Day als~ be used. All of those techIliglles for ormulating and applyi~g fungicides are ~ell k~o~n in the art~
t7 The percen*ages by ~eLght of the fungicid~ may vary 18~ accordi~g t~ the m~nner i~ which the co~position is to be applied 19 and the particula~ type of formulation, but in general ~,omprise 0.5 to 95% ~f the t~ica~t by weight of the fungicidal 21 composition. .`
22 The funqicidal compositions m~y ~e formul3ted and 23 app1ied wst~ other acti~e ingredients, includin~ o~her 24 fungicides, insecti~ides, nematocides, bac~ericides, plan+ gro~
. 25 regulatctrs, fertilizers, etc.
26 EXAMPLES ~
27 The preParatio~ and ~ungicidal activity of the 28 co~pounas of the invention are illustrated by the f~ wing 29 exa~p ' es,.
:
, 3~
E~ample 1 -- Preparat~ on of 3-~N-chloroacetyl- -2 N-2 6-d' m_thYlPhenYlL-qam'~a-bU~Xr~hllaCtae 3 A ~oluti3n of 10 g (0. 055 ~oll alpha-bromo-gamma-4 butyrothiolactone~ 6.68 g ~0.05~ mol~ 2,6-dimethylaniïine and 5.58 g ~00055 mol~ dimethylpyridine was heated at 85-90C ~or 12 6 hoursg The reaction mixture ~as than c~oled, dil~:lted ~ith water 7 and dichlorometha~e. The organic phase ~as separat~d and 8 ~iltered throuqh a short sillca gel column. The filtrate ~as 9 eYaporated under reduced pressure to give an oil reslduP.. ~he 10 residue ~as vashed ~ith 5~ aqueous }Iydrochloric aeid solution, 11 washed ~ith Yater~ a~d dried over ~agnesium sulfate to give 71~2 g 1~ of 3-(N-di~Pthylphenylamino)-gamma-butyrothiolactone. The 13 infrared spectrum o~ the thiolactone product showed strong 14 carhonyl absorption at 5.R8 micron. El~mental analysis for C~zH~UOS sho~ed: ~S, calc. 14.5, founl 14,2 16 ~ solutio~ of 1.52 g (0.0134 ~ol\ chloroace~yl chlorile 17 in 10 ml toluene ~as added dropwise to ~ solution of 2.97 g 18 (0.0131~ mol) 3~ imethylphenylamino)-~amma-bu~yrothi~lac:tDne 79 10~ ml b~nze~:e maintained at reflux temperature~ ~he reaction
~ . .
_ g _ 3~3~
conducted in inert organic solvents, e. g., apolar dipr~tic 2 sol~ents su~h as dim ethylormamide ~nd ~cetonitrile and aro~atic .
3 hydrocarbons s~ch as benzene and toluene, at reactio~ tampera-4 tures Yaryi~lg from 25C to 150C, preferably from soor to 150C. .
Water may be employed as a co solvent. The reac~io~ pressure ~y 6 be a~mospheric, subatmospheric or super~tmospheric. Ho~/ever~ ~r 7 convenience of conducting the rea::tion, the pressure is generally 8 atmospheric. The reaction time will, o~ course, vary depending 9 upon the reactants and the reaction temperature. Ginerally the reaction time is fro~ 0.25 to 24 hours. The product ~X~ is 11 generally purified by conventional procedures, e. g., extraction, 1~ distlllation~ or crystallization, ~efore use in the ac~l~tion 13 reaction (2).
14 Preferred alkylation reaction conditions are given in more detail in the commonly assignea U.SO applicati~n Serial ~o.
16 847,503 of Richard ~. Reynolds, Jr., entltled "Alkyla~ion of :17 Aniline ~i~h a~Lactone in ~he Presence;~f Water", filea o~
18 ~o~ember 1, 1477.
19 : The acylation:reaction (2) is conducted by conventional procedures. The relctants ~X3 and (XI~ are generally contacted 21 in substantially equimolar amounts in an inert orga~ic sol~e~t ~t 22 a temperatura of 0 ~o 100C. Suitable inert organic s~lvents 23 include ethyl a~etate, methylene dichloride, dimethox:yethane, 24 ben~ene, ~t~. The product is isola~ed a~d p~rified by conven-tional procedures such as extraction, distillation~ chr~ma-26 toqraphy, crystalli~ation, etc.
27 Whon pr~paring a butyrolactone product (c3mpou~ds of 28 ~ormula (I) ~herein Y=O3, an orga~ic amina such as a trialkyl-29 a~ine or a pyridine compound may ~e employed as an acid acceptvr.
However, ~hen preparing a but~rothiolac~one proauc~ ~compounds of 31 Pormula (I~ ~herein Y=S~, an organic amine should not ba 32 ~ employed.
~33~
Preferred acylation reaction conditions are given in more detail in the commonly assigned United S-tates Paten-t No.
4,224,453 of Richard N. Reynolds, Jr., Stephen D. Ziman and David C. K. Chan, entitled 'IAcylation of Lactone-Substituted Aniline Compound in the Absence of an Acid ~cceptor", issued on September 23, 1980.
The compounds of Formula (I) wherein Rl is alkylthio-methyl, phenylthiomethyl or substituted-phenylthiomethyl may be prepared from the corresponding compound wherein Rl is halo-methyl by reacting the corresponding halomethyl compound with an alkali metal mercaptide by conventional procedures as depicted ~ ;
in the following equation (3)~
O ~ o ~ :
ll ll Ar-N \ + RSM ~ Ar-N \ + MX (3) I 1 2 1 1 2 ~ -O=C CH-R O=C CH-R
\Y/ ' \y/ : ~
,~ .
wAerein Ar, R , X and Y are as previously defined, M is alkali metal, R7 lS alkyly~ phenyl or substituted phenyl moiety of Rl.
In reaction (3), Y preferably is oxygen.
The compounds of Formula (I) wherein Rl is hydroxy~
methyl and Y is oxygen may be prepared by treatment of the cor-responding compound wherein R is halomethyl with an inorganic alkali metal hydroxide such as aqueous sodium hydroxide. The compounds of Formula (I) wherein Rl is hydroxymethyl and Y is oxygen or sulfur may be prepared by hydrolysis of the corres-ponding compound wherein Rl is alkanoyloxymethyl ~e.g., acetoxymethyl).
The compounds of Pormula (I) wherein R is chloro or bromo are generally prepared by chlorinating or brominating -the `,: ' F'~, ` - - 1 1 -3i,, 3~
3~
1 correspondinq compound vherein R2 is hyarogen with a chlorinating 2 or brominatinq agent such as ~-bromosuc~inimide or N-chlorosuc-3 cinimide by conv~ntional procedures, as depicted in the following 4 equation l4~:
O O O O
,. .. .. ..
C - R 1 C - CH 2 C - R 1 ~C - C ~ 2 Ar-N\ + X-N~ ¦ ) Ar-N\ + HN~
CH lH2 C-CH2 CH--l}12 C--CH2 O=C~ ~CH 2 O=C~ ~CH-X
Y `Y (4) . .
5 wherein Ar, Rl, Y and X are as previously defined.
6 The lactam compounds of the invention ~ay be preparea 7 by cyclizinq a gamma-halo amide (XII) in the presence of a base 8 and subseque~tly acylating the gamma-la~tam (XIII) to gLYe the 3-9 (N-acyl-N-arylamino~-gamma lactam produ_t (~), as depicted in the following equations:
base ~r NH-CH-CH2-CHR2 ~ Rr-NH-CR~ 2 ~HX l l : O=C Br O=C.\ /CHR2 H~IR ~ N (5) (XII) i R
5XIII) o ba5e C-R
~r-NH-CH;- CH2 + X-C-Rl ~ Ar-N
O--C~ ,1HR2 ~HX \CH--I H2 N ~=~\ C_R2 : R N (6) R
~XIII) (I), YsNR
11 ~herein Ar~ R~ Rl, RZ and X ha~e the same significance ~s 12 prev~ously definedO
13 The cyclization reaction (5) is conducted by ~r~ating 14 the gamma-halo (~ ith substantially equimolar z~ou~ts of strong inorganic base, e.g.~ alkali met~l alko~ides such as ;3 3~
sodium me~hoxide, p~tassium ethoxide, etc. O and alkali metal 2 hydrides such as sodium hydride~ ~hen ~n al~ali metal ~lko~ide 3 base is employed, the reaction is preferably conducted in an 4 alkanol solvsnt su~h as methanol and ethanol. Hhsn a~ alkali metal hydriae base is employed, the reaction is preferably 6 conducted i~ a polar non-hydric oxyge~ated sol~e~t such as 7 dimethoxyet.hana. ~he lactam product (XIII) is purified by 8 convantional prosedures such as ext~action, distillatio~ chrom~-9 to~raphy or crystallization before use in the ac~ylation reaction .
~6).
11 The acylation reaction (6) is conducted in the presence 12 o~ an orqanic amine base by the same procedure disclosed above 13 for reaction (2).
14 The gamm -halo ~eactant (XII) is suitably prepared by 15 halogenating by con~entional procedures, e.g.~ ~lth phosphorus 16 tribromide or thionyl chloride, the corresponding gamma-hydroxy, 17 :i.e., ~he co~pound o:f formula (XIV):
18 ~ Ar-NH-CH-CH~-CElRZ (XIVj 19 . . I
O=C OH
23 The ga~ma-hydro~y fXIV) in turn is prepared by reacting 24 the 3-N-arylamino)-3amma-lactone ~X) with ammonia or an amine 2~ tH2~R) in an inert solvent at a temperature of ~5~ to 100C~ an~
2~ subsequently purifying th~e product by c~nventional pro~ures.
27 UTILIqlY
28 The co~pou~ds of ~he inYention are useful for 29 controllinq ungi, par~icularly plan~ fungal infec~ionsO
~owever, some fungicidal compositions of the invention may be 31 more fungicidally active than others ag~i~st partic~lar fungi.
32 For example, the activity of the preferred co~pounds of the 33 inYenti~n is highly specific for certain fungal diseases such as^
~33~
1 downy milde~s, e.g., PlasmoPara Yit~CQla ~grapes~ and PQEono~oEa 2 Darasitic3 (cabbage and collard), late blights" e.g., 3 PhvtoPhthQEa infestans (tomatoes and potatoes)~ and cro~n and 4 root rots, e.g., PhYto~hthorL-S The ~ompounds of the in~entio~ are particularly useful 6 funqicides because they cure establishe~ fungal inf~cti~ns. This 7 per~its aconomical use of the fungicides of the invention, 8 because ~hey need n~t be applied to plants unless fungal 9 infection actually occurs. q~huso a preventative progr~ of applying fungicides against potential ungal infectio~ is not 1 1 necessary.
12 Uhen used as fungicides, the ~ompounas of the in~enti~n 13 are applied in fungicidally effective amounts to fungi and~or 14 their habitats, su~h as vegetative ~osts and nonvegetative hosts, e.g., animal products. The amount used ~ill, of course, depend 16 ~ on several factors such as the host, the type of fungus a~d the 17 particular compoun~ of the in~ention. As with most pesticidal 18 co~pou~ds,: thç fu~ngicides o~ the inve~tion are not usually 19 applied ~ull strength, bu,t are generally incorporated irith conventiollal, biolsgically inert extenders or carriers normally 21 employed f~r facilitating dispersion of active fungicia 22 compounds, recognizing tha~ the formulation a~a ~ode of 23 applicatlon may affect the activity of the ~ungicide. Thus, the 24 fungicides of the inventio~ may be formulated and applied as granules, as poYdery dusts, as wettable powders, as emulsifiable -26 concentrates, as solutions, or as any of several other known 27 types of formulations, dependiny on the desired mode of 28 application.
29 ~ettable po~ders are in the form of finely di~ided particles which dispers readily in water or other dispersant.
31 These compositions normally contain fro~ about 5-BOS fungicide, .
, .
33~
1 and the rest inert material, which ~ncludes dispersing ~gen~s, 2 emulsilying agents ~nd wetting ag~nts. The powder ma~ ~e applied 3 to Ihe 60il as a dry dust, or preferably as a suspension in 4 ~ater. T~pical carriers i~clude fuller~s earth, ka~lia clays, silicas, an~ other highly absorbent, slettable, inorgani~
~iluents. rrpical wetting, ~ispersing ~r e~uls~fyirlg ~gents 7 include, ~or examPle: the aryl and alkylaryl sul~onates and 8 their so~ium s~lts, lkylamide sulfonat~s9 includin~ f~tty methyl 9 taurides; alkylaryl polyether alcohols, sulfated hiqher alcohois and polyvinyl ~lcoh~ls; polyethylene oxiaes, sulfonatea animal 11 and ~eq~table ~ils sulfonated pstroleu~ oils, fatty a~id asters 12 of polyh~aric alcoh~ls and the ethylene oxide addition products 13 OI such es~ers; and the addition products of long-chain 14 merc:aptans and ethylcne oxide. Many other typ~s of useful surface-acti~e ageDts are avallable in ~ommerce., The surrace-16 active aqent, whe~ used, normally comprises from 1~ to 15~ by 17 ~eight of the funqicidal co~position.
18 Dusts are freely~flow1n~ admixtures of tha a~tive 19 ; funqi~ide ~ith fi~nely di~ided solids su_h as~t~lc, natural clays, kieselguhr, pyrophyllite, chalk, diatom~ceous earths, c~lciu~
21 phosphates, calcium and magnesium carbonates, sulfur, lime, 22 flours, and other orqanic and inorganic solids whi~h a~t as 23 dispersants and ~ar-rlers for ~he toxicant~ These finely divide~
24 solias have an average part~cle size of less than about S0 microns. ~ typical dust for~ulation useful herein co~tains 75%
26 silic~ a~d 25~ ~f the toxicant.
27 Useful liquid c~ncentrates include the emulsifiable 28 concentrates, ~hich are ho~ogeneous liguid or paste compositions 29 ~hich are readlly aispersed in water or o~her dispersant~ a~d m~y consist en~irel~ of the fungicide wi~h l liquid or solid 31 emulsifying aqent, or may also contain ~ liquid ~arrier such as 3~;~
xylene, heaYy aromat ic naphthast~ isophorone, and other 2 nonvolatile organic solvents. For appli~atioi, these.
3 concentrates are dispersed in water or other liquid carrier, ana 4 sre r,ormally applied as t spray to the ~rea to be treated.
~ther useful formulations for fungicidal 2pplications 6 include simple solutions of the active fungicide ~n a dispersant 7 in which it is completely soluble at the desired concentration, 8 such as acet~n~ ~ alkylated naphthalenes~, xylene, or oth~r organi ~ -9 solvents. Granular formulatio~s, ~herein the fungicide is carried on rela'iYely coarse particles, are of particular utility 11 for aerial aistri~utiorl or for penetration of aover-crop canopy~
12 ~ressurizea sprays, typically aerosols wherein the active 13 ingredient is dispersed in finely dividad form as a result of 14 vaporizatio~ of a lo~boiling dispersant solvent carrier, su~h as the Freons, Day als~ be used. All of those techIliglles for ormulating and applyi~g fungicides are ~ell k~o~n in the art~
t7 The percen*ages by ~eLght of the fungicid~ may vary 18~ accordi~g t~ the m~nner i~ which the co~position is to be applied 19 and the particula~ type of formulation, but in general ~,omprise 0.5 to 95% ~f the t~ica~t by weight of the fungicidal 21 composition. .`
22 The funqicidal compositions m~y ~e formul3ted and 23 app1ied wst~ other acti~e ingredients, includin~ o~her 24 fungicides, insecti~ides, nematocides, bac~ericides, plan+ gro~
. 25 regulatctrs, fertilizers, etc.
26 EXAMPLES ~
27 The preParatio~ and ~ungicidal activity of the 28 co~pounas of the invention are illustrated by the f~ wing 29 exa~p ' es,.
:
, 3~
E~ample 1 -- Preparat~ on of 3-~N-chloroacetyl- -2 N-2 6-d' m_thYlPhenYlL-qam'~a-bU~Xr~hllaCtae 3 A ~oluti3n of 10 g (0. 055 ~oll alpha-bromo-gamma-4 butyrothiolactone~ 6.68 g ~0.05~ mol~ 2,6-dimethylaniïine and 5.58 g ~00055 mol~ dimethylpyridine was heated at 85-90C ~or 12 6 hoursg The reaction mixture ~as than c~oled, dil~:lted ~ith water 7 and dichlorometha~e. The organic phase ~as separat~d and 8 ~iltered throuqh a short sillca gel column. The filtrate ~as 9 eYaporated under reduced pressure to give an oil reslduP.. ~he 10 residue ~as vashed ~ith 5~ aqueous }Iydrochloric aeid solution, 11 washed ~ith Yater~ a~d dried over ~agnesium sulfate to give 71~2 g 1~ of 3-(N-di~Pthylphenylamino)-gamma-butyrothiolactone. The 13 infrared spectrum o~ the thiolactone product showed strong 14 carhonyl absorption at 5.R8 micron. El~mental analysis for C~zH~UOS sho~ed: ~S, calc. 14.5, founl 14,2 16 ~ solutio~ of 1.52 g (0.0134 ~ol\ chloroace~yl chlorile 17 in 10 ml toluene ~as added dropwise to ~ solution of 2.97 g 18 (0.0131~ mol) 3~ imethylphenylamino)-~amma-bu~yrothi~lac:tDne 79 10~ ml b~nze~:e maintained at reflux temperature~ ~he reaction
20 ~ixtDre ~as he~ted at re~lux until the 2volution o~ hydrochlori~e
21 gas ceased (about 3 hours)~ cooled, and evaporated unaer reduce~
22 pressure to giYe a brown solid. Recrystallization fro~
23 isopropanol qave 2.5 g of 3-~N-chloroac tyl-N-2,6-di~ethyl-
24 phenylamino~-gamma-butyrothiolactone, as tan crystals, ~p7 13B-
25 13gC~, The inf~ared spectrum of the pr~duct sho~ed t~o strong
26 carbonyl absorption bands at S. 88 microns and 6.02 microns.. The
27 product is tabulated ir~ Table A as Co~pourld No. A-1.
28 Example 2 -- Preparatio~ o~ 3- lN-chloroacetyl-N-2-
29 chloto-6-methvl~he~lalninQ~-gamm~-butyroth Qla~tQr'e ~ solution of 8 g t0.044 mol) alpha-~romo-gamma-but~ro-31 thiola~tone, 6. 23 g (0. 044 mol) 2-chlor~-6-methylaIIilina and 4.7 32 g l0.044 moll 2,6-d~ ~e~hylpy~idine was heated for about 16 hours .
33~
1 at about 95C under a nitroge~ atmosphere. The rsactio~ mixture 2 was co~led, diluted ~rith 60 ml dichloromethane, washed ~i*h 3 water, washad with 10~ agueous hydrochloric acid, a~d filtered.
4 The filtrate vas dried over magnesium sulfate arld evaporated 5 ` und~r reduced pressure to give a dark vi~cous residue. The 6 residue was eluted through a short sili-a gel chro~atography 7 column with dichloromethane. ~he produ~t-c~taini~g fractions 8 vere stripped to giYe 4.59 g of 3-~N-2-chloro-S-methyl-9 phen~la~in~)-q~mma-butyrothiolactone. ~hin-layer chrom~tography -of the pr~duct sho~ed one large spot. The infrared spe~ um o 11 the product showed strong. carboDyl a~sorption at 5.:88 micro~s aG~
12 the nuclear maqne~i~ resonance spectrum shoNed a 3-proton singlet 13 for the methyl group at 2.33 ppm (relative to tetramsthylsilane~.
14 A solution of 2015 g (0.019 m~l) chloroacPtyl chloride i5 in 10 ml toluene was added dropwise. to ~ refluxi~g solution of 1 6 4.59 g t0.019 mol) 3 (N-2-chloro-6-methylphenylamin~) -gamma-17 butyrothiol~torle iu 150 ml toluene. The reaction'mixture ras t8 heated at reflux~ f~r about 7 hours (HC1 was e~olv~d~, s~ir~e~
19 ~a~out 16 h~rs at 25C and evaporated ~under r~duced pressure to give a dark resi;due~ ~hin-layer chromatography of the residue 2~ showed two SPots. rhe residue was chro~atographed thr~ugh a 22 silica-geï column with acetone/dichloronetha~e elutionThe 23 chromatographic ~r~ctions containing the second material eluted 24 from the c:olumn ~ere combined and evaporated to give the desirea productt ~hich was crystallized from isopropyl alcohol to give 26 . 0.98 g of proauct, ~s a bro~n solid, m.p. 133-137~C. The 27 infrared spe~trum of the product showed t~o s~rong carbonyl 28 absorption banas at S.84 microns and 5.95 microns. The compoun~
29 is tabulated in Table A as Compound No. A-3 , ~ - 18 ~
.
3~i Exampl~ 3 -- Preparation o~ 3-(N methoxymethyl-2 L=2.L6-aime~hYlPheTl~laminQL-~amma-butyEothiol~ct-one 3 A solution of 1046 g (~.0135 mol) ~thox~acet~1 4 chloride in 10 ml dichloromethane was aaded drop~i~e to a refluxi~g solu~ion of 3 g (0.0135 mol) 3-(N-2~6-dim~thylpheny-6 amin3~-gamm~-butlrr~thiolactone .ill 2û0 ml tolu~neO rhe reac~ion 7 mi~ture ~as heated ~ t reflux for 3 hours and e~raporated to give 8 solid. ~he solid as recrystallized from a 10:~:10 solYent 9 mix~ure of e~her:benzen~:he~ane to ~ive 1O8 g o~ ~he pr~duct, 35 10 a tan solid, m. p. 86-87C. The in~ar~a spectrum of th~ product 11 sho~red t~o strDrlg _~rbonyl absorption b nds at 5. 85 microns a~d 12 6. 03 m' ~rons. l~he product is tabulated in Table A ~s C~pound 13 No. A~
14 Example 4 -~ Preparation of 3- (N-chloroacetyl-N 2, 6-dlm~-~hV1~h~BYlam1BL_5-ch~ a_mma-b.utyro1~cton,e 16 A slurry of 16 g (0.06 mol) of 3 (N-chloroacetyl-~-2,6 17 dimethylphenylamin~-gamma-:butyrolactone, 11 g (0.08 mol) N-18 chlorosucci~i~îde ~nd 0.~ g benzoyl per~xide i~ 200 ml -arbo~
19 tetra~hloriae ~ras heatea u~der reflux fDr 1~ hours,- The reacti~n :
2û ~ixture uas cooled to abou~ 2~C. A solid separated. The solia 2~ was filtered from the reac~ion mixture ~nd ~ashed vith 200 ~1 22 dichloro~ethane~, The moth~r .liguor ~as ~ashed with ~ater, driea 23 over magnesiuD1 sulfate and evaporated under reduced pressure t~
24 qilre an oil residue~ The residue ~s crystallized from e~her t~
give 19.5 q of proauct, ~.p. 103-10~C. This produ~,~ is 26 tabulated i~ T~ble B as Compound No. ~
27 Example 5 - Preparation of ~ acetoYyac2tyl-28 N-2,6-dimeth~l~he~Ylam-noL-g~m~a-bU~X~la~a`e 29 A 13.7-g (0~ ol) sample of acetoxyacetyl chloride ~as add~d drop~ise to ~ solut o~ of 20.~ g ~0.1 mol) ~-2t6-aimethyl-31 phenylamino-gamma-butyrolactone and 7~9 g (0.1 mol~ pyridi~e i~
32 150 ml benzene. After comp~etion of the addition~ th~ reactio~
~33~
1 ~ixture was stirre~ at about 25~C ror 4 hours, then washed vith 2 ~ater, dried over magnesiu~ sulfate and evaporated ~nder reducea 3 pressure to give an oily residue~ The residue was ~rystallized 4 from ethyl ether~he~ane to give 27.3 g of product~ m.p~ 90~91C~
S This product is tabulated in Table B as Compound No. B-2.
6 E~ample 6 -- Preparation of N-hydroxyacetyl-7 N-2~5~6-di~ethyl~henylam~no-ga--~a-butyEolat-ne 8 A solution of 50 g (0.1a mol) 3-(N-chloroacetyl-N--2,6-9 dimethylphenylamino~ gam~a-butyrolactone, 14.5 g (0.36 ~ol~
sodiu~ hydroxide dissolved in 50 ml vaterO a~d 450 ml ~imetho~y-11 ethane was stirred at about 25C f~r 16 hours. The resQlting 12 rea~tion mixture w~s filtered, dil~lted ~ith 500 ml dichloro-13 ~ethane. Hydrogen -hlor1de gas ~as bubbled into the reaction 1~ mixture for 1 hour~ T~e reaction mixture ~a's filtered, dried o~er magnesium sul~ate~ and evaporated ~nder reauced p~ssure.
16 The residue was washed ~ith 10% ethyl ether~90~ ~e~a~e, ~ilt~re~
t7 and air--dried to :giYe 36.5 g of the product as a white .
18 crystalline solid, m.p. 173-174C. The product is tabulated in 19 ~able B as ~ompouna ~o. B-3.
Exa~ple 7 -- Preparation of N-ethoxya~etyl-21 N=2~6-dl~eth~lphenylamlno-~amma-butyrolactone 22 A 6.2-g (0.05-mol) sa~pls of etho~yacetyl chl~ride uas 23 added aropwise to a refluxing solution of 10O3 (O.OS m~l~ 3-(N-24 ~ 2~6-di~etsylphenylami~o) gamma-butyrolactone in 150 ml toiuerle.
25 ~ho r~ac~ion mi~ture Yas then heated uni er reflu~ for 2 hours.
26 After coolinq, the reactio~ mixture was washed ~,rith water, ~ash~
27 with saturated sodium bicarbonate solution, ~ashed vith ~ater~, 28 dried o~er ~agnesiu~ sulfate and evapor~ted to give 11, 2 g of 3-29 (~eth~yacetyl-N-2r 6 di~ethylph~nylamin~)-gam~a-butyrolactQne,
33~
1 at about 95C under a nitroge~ atmosphere. The rsactio~ mixture 2 was co~led, diluted ~rith 60 ml dichloromethane, washed ~i*h 3 water, washad with 10~ agueous hydrochloric acid, a~d filtered.
4 The filtrate vas dried over magnesium sulfate arld evaporated 5 ` und~r reduced pressure to give a dark vi~cous residue. The 6 residue was eluted through a short sili-a gel chro~atography 7 column with dichloromethane. ~he produ~t-c~taini~g fractions 8 vere stripped to giYe 4.59 g of 3-~N-2-chloro-S-methyl-9 phen~la~in~)-q~mma-butyrothiolactone. ~hin-layer chrom~tography -of the pr~duct sho~ed one large spot. The infrared spe~ um o 11 the product showed strong. carboDyl a~sorption at 5.:88 micro~s aG~
12 the nuclear maqne~i~ resonance spectrum shoNed a 3-proton singlet 13 for the methyl group at 2.33 ppm (relative to tetramsthylsilane~.
14 A solution of 2015 g (0.019 m~l) chloroacPtyl chloride i5 in 10 ml toluene was added dropwise. to ~ refluxi~g solution of 1 6 4.59 g t0.019 mol) 3 (N-2-chloro-6-methylphenylamin~) -gamma-17 butyrothiol~torle iu 150 ml toluene. The reaction'mixture ras t8 heated at reflux~ f~r about 7 hours (HC1 was e~olv~d~, s~ir~e~
19 ~a~out 16 h~rs at 25C and evaporated ~under r~duced pressure to give a dark resi;due~ ~hin-layer chromatography of the residue 2~ showed two SPots. rhe residue was chro~atographed thr~ugh a 22 silica-geï column with acetone/dichloronetha~e elutionThe 23 chromatographic ~r~ctions containing the second material eluted 24 from the c:olumn ~ere combined and evaporated to give the desirea productt ~hich was crystallized from isopropyl alcohol to give 26 . 0.98 g of proauct, ~s a bro~n solid, m.p. 133-137~C. The 27 infrared spe~trum of the product showed t~o s~rong carbonyl 28 absorption banas at S.84 microns and 5.95 microns. The compoun~
29 is tabulated in Table A as Compound No. A-3 , ~ - 18 ~
.
3~i Exampl~ 3 -- Preparation o~ 3-(N methoxymethyl-2 L=2.L6-aime~hYlPheTl~laminQL-~amma-butyEothiol~ct-one 3 A solution of 1046 g (~.0135 mol) ~thox~acet~1 4 chloride in 10 ml dichloromethane was aaded drop~i~e to a refluxi~g solu~ion of 3 g (0.0135 mol) 3-(N-2~6-dim~thylpheny-6 amin3~-gamm~-butlrr~thiolactone .ill 2û0 ml tolu~neO rhe reac~ion 7 mi~ture ~as heated ~ t reflux for 3 hours and e~raporated to give 8 solid. ~he solid as recrystallized from a 10:~:10 solYent 9 mix~ure of e~her:benzen~:he~ane to ~ive 1O8 g o~ ~he pr~duct, 35 10 a tan solid, m. p. 86-87C. The in~ar~a spectrum of th~ product 11 sho~red t~o strDrlg _~rbonyl absorption b nds at 5. 85 microns a~d 12 6. 03 m' ~rons. l~he product is tabulated in Table A ~s C~pound 13 No. A~
14 Example 4 -~ Preparation of 3- (N-chloroacetyl-N 2, 6-dlm~-~hV1~h~BYlam1BL_5-ch~ a_mma-b.utyro1~cton,e 16 A slurry of 16 g (0.06 mol) of 3 (N-chloroacetyl-~-2,6 17 dimethylphenylamin~-gamma-:butyrolactone, 11 g (0.08 mol) N-18 chlorosucci~i~îde ~nd 0.~ g benzoyl per~xide i~ 200 ml -arbo~
19 tetra~hloriae ~ras heatea u~der reflux fDr 1~ hours,- The reacti~n :
2û ~ixture uas cooled to abou~ 2~C. A solid separated. The solia 2~ was filtered from the reac~ion mixture ~nd ~ashed vith 200 ~1 22 dichloro~ethane~, The moth~r .liguor ~as ~ashed with ~ater, driea 23 over magnesiuD1 sulfate and evaporated under reduced pressure t~
24 qilre an oil residue~ The residue ~s crystallized from e~her t~
give 19.5 q of proauct, ~.p. 103-10~C. This produ~,~ is 26 tabulated i~ T~ble B as Compound No. ~
27 Example 5 - Preparation of ~ acetoYyac2tyl-28 N-2,6-dimeth~l~he~Ylam-noL-g~m~a-bU~X~la~a`e 29 A 13.7-g (0~ ol) sample of acetoxyacetyl chloride ~as add~d drop~ise to ~ solut o~ of 20.~ g ~0.1 mol) ~-2t6-aimethyl-31 phenylamino-gamma-butyrolactone and 7~9 g (0.1 mol~ pyridi~e i~
32 150 ml benzene. After comp~etion of the addition~ th~ reactio~
~33~
1 ~ixture was stirre~ at about 25~C ror 4 hours, then washed vith 2 ~ater, dried over magnesiu~ sulfate and evaporated ~nder reducea 3 pressure to give an oily residue~ The residue was ~rystallized 4 from ethyl ether~he~ane to give 27.3 g of product~ m.p~ 90~91C~
S This product is tabulated in Table B as Compound No. B-2.
6 E~ample 6 -- Preparation of N-hydroxyacetyl-7 N-2~5~6-di~ethyl~henylam~no-ga--~a-butyEolat-ne 8 A solution of 50 g (0.1a mol) 3-(N-chloroacetyl-N--2,6-9 dimethylphenylamino~ gam~a-butyrolactone, 14.5 g (0.36 ~ol~
sodiu~ hydroxide dissolved in 50 ml vaterO a~d 450 ml ~imetho~y-11 ethane was stirred at about 25C f~r 16 hours. The resQlting 12 rea~tion mixture w~s filtered, dil~lted ~ith 500 ml dichloro-13 ~ethane. Hydrogen -hlor1de gas ~as bubbled into the reaction 1~ mixture for 1 hour~ T~e reaction mixture ~a's filtered, dried o~er magnesium sul~ate~ and evaporated ~nder reauced p~ssure.
16 The residue was washed ~ith 10% ethyl ether~90~ ~e~a~e, ~ilt~re~
t7 and air--dried to :giYe 36.5 g of the product as a white .
18 crystalline solid, m.p. 173-174C. The product is tabulated in 19 ~able B as ~ompouna ~o. B-3.
Exa~ple 7 -- Preparation of N-ethoxya~etyl-21 N=2~6-dl~eth~lphenylamlno-~amma-butyrolactone 22 A 6.2-g (0.05-mol) sa~pls of etho~yacetyl chl~ride uas 23 added aropwise to a refluxing solution of 10O3 (O.OS m~l~ 3-(N-24 ~ 2~6-di~etsylphenylami~o) gamma-butyrolactone in 150 ml toiuerle.
25 ~ho r~ac~ion mi~ture Yas then heated uni er reflu~ for 2 hours.
26 After coolinq, the reactio~ mixture was washed ~,rith water, ~ash~
27 with saturated sodium bicarbonate solution, ~ashed vith ~ater~, 28 dried o~er ~agnesiu~ sulfate and evapor~ted to give 11, 2 g of 3-29 (~eth~yacetyl-N-2r 6 di~ethylph~nylamin~)-gam~a-butyrolactQne,
30 mOp. 73_75al:~. The product is tabulated in Table B ~s CDmpound
31 No. B--9.
33~
Example 8 - Preparation of N-~ethylthioacetyl 2 N-2 6-d_methyl~hsnYlamlaO qa~a-butyrolacto~
3 A 2~-g (0. 3-mol~ sample of so~ium ~ethyl~ercaptide was 4 added in small portions ~c:) a solution of 25. 3 g tO~,08 ~1) N~
S bromoacetyl-N-2 t6-d~ m~thylphenylamino) -gamna-butyrolact4ne, ~.p.
6 116-117C, i~ 200 ml dimethyl sulfoxide. A mild ex~herm ensua 7 The _eaction mistllre uas allowed ~o s~ir at a~ou~ 25C f~r about 8 16 hours. Th~ rea~'cion mixtur~ was then heated to about 15ûC
9 under reduced vatsr aspira'cor prassure to remove a portion of the 10 dimethyl sulfo~ide solvent. The residu2 ~as diluted with srater 11 ar.d th~ agueous layer separatea.. The or~anic portio~ w~s 12 dissol~ed in 350 ml dichloromethane, washed with ~ater, dried 13 oYer magn~sium sulfate and eYapora~ed und~r reduced pressure to 14 give an oiL The oil ~as chro~atog-aphed through a silica gel 15 column (20% acetone/80X petroleum e~her elution) to give the 16 product (11 gl, vhl~h after crystallization from ethyl .
17 ether~/acetone melted at 77-7~C. The product is tabulated in 18 Table B as Compo~nd No. ~B~
19 Example 9 -- Preparation of 3-(N-chloroace~yl--2-meth~Lna~hth,_l_Ylam_n~L-~2~ma-bU~rQlaCtne-21 ~ 200-ml roundobottom flàsk eguipped with a heating 22 mantle a~d connectea to a water aspirator vacuum syste~ ~as 23 chargea ~ith 15~0 g ~0~1 mol) 1-ami~o-2-methylnaphthalene, 16.4 g 24 (0.1 mol3 alpha-br~o-gamma-butyrolactone a~d 10~7 g ~0.1 ~ol~
25 296-dimeth~lprriaine~ The reaction mixt~re ~ias maintai~ed at 26 about 94-101C and 160 mm of Hg for a~oll~. 7 hours. The rea~tion 27 u~ixture was cooled, diluted vith 100 ml acetone and tilterea.
28 ~ ~he fil~ra~e ~as evaporated u~der reduced pressure to give ~n 29 oily residue which ~as eluted through ~ s1lica gel ~olu~n ~ith 15% acetone~85~ petroleum et}ler to give 14.6 g of 3- (N-2O~ethyl~
31 naphth- l-ylamino) -qam~a-butyrolactone, m . p. 92-94C. 21eme~tal
33~
Example 8 - Preparation of N-~ethylthioacetyl 2 N-2 6-d_methyl~hsnYlamlaO qa~a-butyrolacto~
3 A 2~-g (0. 3-mol~ sample of so~ium ~ethyl~ercaptide was 4 added in small portions ~c:) a solution of 25. 3 g tO~,08 ~1) N~
S bromoacetyl-N-2 t6-d~ m~thylphenylamino) -gamna-butyrolact4ne, ~.p.
6 116-117C, i~ 200 ml dimethyl sulfoxide. A mild ex~herm ensua 7 The _eaction mistllre uas allowed ~o s~ir at a~ou~ 25C f~r about 8 16 hours. Th~ rea~'cion mixtur~ was then heated to about 15ûC
9 under reduced vatsr aspira'cor prassure to remove a portion of the 10 dimethyl sulfo~ide solvent. The residu2 ~as diluted with srater 11 ar.d th~ agueous layer separatea.. The or~anic portio~ w~s 12 dissol~ed in 350 ml dichloromethane, washed with ~ater, dried 13 oYer magn~sium sulfate and eYapora~ed und~r reduced pressure to 14 give an oiL The oil ~as chro~atog-aphed through a silica gel 15 column (20% acetone/80X petroleum e~her elution) to give the 16 product (11 gl, vhl~h after crystallization from ethyl .
17 ether~/acetone melted at 77-7~C. The product is tabulated in 18 Table B as Compo~nd No. ~B~
19 Example 9 -- Preparation of 3-(N-chloroace~yl--2-meth~Lna~hth,_l_Ylam_n~L-~2~ma-bU~rQlaCtne-21 ~ 200-ml roundobottom flàsk eguipped with a heating 22 mantle a~d connectea to a water aspirator vacuum syste~ ~as 23 chargea ~ith 15~0 g ~0~1 mol) 1-ami~o-2-methylnaphthalene, 16.4 g 24 (0.1 mol3 alpha-br~o-gamma-butyrolactone a~d 10~7 g ~0.1 ~ol~
25 296-dimeth~lprriaine~ The reaction mixt~re ~ias maintai~ed at 26 about 94-101C and 160 mm of Hg for a~oll~. 7 hours. The rea~tion 27 u~ixture was cooled, diluted vith 100 ml acetone and tilterea.
28 ~ ~he fil~ra~e ~as evaporated u~der reduced pressure to give ~n 29 oily residue which ~as eluted through ~ s1lica gel ~olu~n ~ith 15% acetone~85~ petroleum et}ler to give 14.6 g of 3- (N-2O~ethyl~
31 naphth- l-ylamino) -qam~a-butyrolactone, m . p. 92-94C. 21eme~tal
32 a~alysis f~r C~,sH~!,jNO2 showed: ~C, cal_. 75.0, found 74.5; %H,
33 calc~ 599, ~ound 5.6; ~N, calc. 5.8, found ~.6, .
33~
A 2.4-q (0 .021 mol) sampl~ ~f chloroacetyl chlDridQ ~s 2 added to a refluxing solu~ion o 5.0 g (0.021 mol~ 3-(N-2-methyl-3 naphth-l-ylamino)-qamma-butyrolactone in 100 ml tolue~e. The 4 reaction mixture was heated under reflux for 30 minutes. Gas ~lS
5 evolved and a ~hite precipitate formed ~uring the 30~mi~ute 6 reflux period. The reaction mixture was coQled, washed ~ith 7 ~at~r, ~ied o~er m3gnesium sulfate and evaporated under reducea 8 pressure to give 4.3 g of p~oduc~, as a white solid, m.p. 121 9 122Co The irlfrared spectrum of the pr~duct sho~ed t~o stro 10 carb~yl abs~rptio~ bands at 5. 62 micror.s and S. 8B ~icrons. Th~
11 proauct is tabulated in Table C as Co~pound No,. C~1r 12 Example 10 -~- Prep~ratior. of 3-[N-methoxymethyl-13 N-2-m_thYlnaP-th~ a~i~noL-aa~ma-bu~yro~ tOne 14 A 2. 4 g ~0 . 022 ~ol) sample of methoxyacetyl chloride lS ~as added drop~ise to a solu~ion of '5.5 g (0.022 mol) 3-~N-2-16 methylnaph~h-1-ylamino~-gamma-butyr~7acto~e and: 107 g (OoQ22 mol~
17 pyridine in 100 ml aichlorome~harle. Th~ reaction ~i~ture w~s :: .
~-~: 18 stirred one ~hour at about 25G and the~ heated under reflu~z for 6 19 hours . After ~ooli~ g o~ernight, the re~ction mixture ~as ~ashea I
suc~essively with water, saturated sodium hicarbonate solution, 21 water9 dried o~er magnesium sulfat~ and e~aporatsd u~der reduce~
22 pressure. ~he resiaue was chromatographed through ~ silica gel 23 column. Elution with 25% acetone/75~ petroleum ether g~ve 4.3 3 .
24 of the produ~t, m.p. 42-46C. The product is tabulated in ~a})le 25 C as Compound Ito. ~-2.
26 Example 11 ~- Preparation of 3~ (N-chloroacetylo 27 N=2L6-_ methYlE!heaQlaminL-qamma-bUtX~laCt~e 28 a solution of 410 g ~2 mols) N-2,6~di~ethy}phany}amin~-2g gamma bu~yr~lacton~, mOp., 85~86.5C, ana 197.5 g (2, 5 m~ls) 30 pyridine i~ 2 li~ers be~zene s~as heated o re~lux. To the 31 sDlut~ on was added arop~dise ~60 g (2. 3 E~ols) chloro~cetyl 32 ~hloride over a 40-minute period. The reaction mixt ure ~as 33~
1 heated under reflux for 20 additional minutes/ cooled and 2 filtered to remove a precipi~a~e of pyridine hydr~chloride. The 3 filtrate ~2s washed ~ith ~ater, dried over magnesiu~ sulfats and 4 evaporated u~der reduced pressure to g~ve a colorless white 5 solid. The solid was slurried ~ith isopropanol, ~iltered~ and 6 dried to give S01 g of product, as a colorless 501i~, m. p. 145. 5-7 1 47~ .
8 The produ-t has an oral LD5n (rats~ of >1000 mg~kg a~d 9 derl~al LD~o (~ats~ ~f >2000 mgfkg. The product is tabulatea in Table D as _ompoun~ No. D-8~
11 Example 12 -- Preparation of 3-~N-chloroacetyl-12 N-2~6-~ methrlehenvlaminoL-s-mgth~l-aamma-but~rol~-toBe : 13 a 500 ml round-bottom flask eguipped with a t~D-way 14 stopcoc~ was cbarged ~ith 24~2 g (0~2 mol) 2,6-dimethyla~iline and 19. 0 q ~0.106 ~lj alpha-bromo gamma-~alerolactone. The 16 flask was evac~ate~ to 20 mm of Hg, then slovly heated to 100C
17 ~hile perioaically eYacuating *he flask by means of a w~ter- - :
18 aspirator t~ ~aint~in the pressure at about 17-40 mm o~ Hg.
19 After hea~lng th~ reaction mixture at about 100~C and at 17-40 ~m o}~q ~or ~2 h~ursj the reaction mixtur~ ~a-Q cooled and dilutea 21 with 300 ml ethyl ether. A solid precipitate of 2,6-dimethyl~
22 aniline hydrobromide salt ~as removed by filtration. ~he 2~ filtra~e was ~ashed with 5% aqueous hydrochl~ric acid solution, 24 ~ater, dried over ~agnesium sulfate and evaporated under red~ce~
pressur~ to:gi~e 19.2 g of 3~ 2,6-dim~thylphenylami~o~-5-26 methyl-gamma-but~solactone, as a viscous oilO
27 a 10. 9-g ~Q.096-mol) sample of chloroacetyl chloride 28 ~as added slo~l~ to a solution of 19.2 ~ (0.088 mol) 3-(N-2,6- ;
29 di~ethylphsnylaminD) -5-me*hyl-gamma-butyrolactone and 7.6 g (0O 096 mol) p7ridifle in 250 ml ethyl acetate. A~ exother~ ensued 31 and a precipitat~ separated. After stirring for 16 hours at ' , ~3L33~
.
about 20C, the rea~tion mixture was washed ~ith uater, vashed 2 uith saturated aqueous soaium bicarbonate solution, washed ~ith 3 uater, dried over magnesium sulfate and evaporated under reduce~
4 pressure to give a thick oil which crystallized from ethyl ether to qi~e a qellou solid. ~hs yellow solid was ~ashe~ vith cold 6 ethyl ether~petroleum ether and air-dri~d to give 15.8 g of 3-~N-7 chloroacetyl-N-2,6~ ethylphenylamino~-5-methyl-gamma^
8 butyrolactone, m.p. 128-131C. The pr~uct is ta~ulated in ~able 9 D as Compound No~ ~-14.
lQ E~ample 13 -- Prepara~ion of 3-~N-propionyl-~ 3~4-d chloro~henylam-nQL-~amma-butxrolacto~Q
12 A reaction flask was charg6d with 32~4 g (0.2 mol) of 13 3,4-dichloroaniline and 16. 5 g tO. 1 ~ol alpha-bro~o-gamma 14 butyrolactone. The f}ask was eYacuated to 20 ~m of Hg ~nd then lS slo~ly hea~ed to 110-14~C. ~he r~action pressure increased to 16 88 mm of Hq, Aftar maintaining at about 23 mm of Hg and 120C .
1i for 1 hour,: the rea~,tion mixture ~as co~led to give a ~olid 18 m}~ture of 3~4-dichloroanillne hyd~robro~id0 sall: and~ 3-(N-3, 4-19 aichlorophe~ylamino)-ga~ma butyrolactoneO The ~ixture ~as treated with ma~h71en~ chloride ~and filt~red. The filtrate ~as 21 evaporated to give the lactone product ~X), Ar=3,4-dichlor-22 phenyl, R and ~Z=H~ and Y=O ].
23 A solutl~n of 5~9 g ~0.~24 ~ol) 3-(N-3~4-dichloro~
24 phenylamino)-gamma-butyrolactone, 2.1 g ~0.026 mol) pyridi~e ang 2~4 g ~0.026 mol) propionyl chloride in 110 ml ethyl acetate ~as 26 heated at 45C. ~fter 1/2 hour at 453C, thin-layer 27 chromatoqraphic analysis showed substantial amoun~s of the . 28 lactone reaclant. Another 2.1 g pyridi~e and 2. 4 9 propionyl : 29 chloride Yere added to ~he reaction mixture. ~he reaction ~ixture ~as ~hen he~ted at refLux for 1/2 hour, cooled, pashed 31 with water, 10~ aqueous sodium bicarbon~te, vater; dried o~er .:
~ - 2~ - .
- .
3 3~
1 magnesium sulfate and evaporated to give an oil. The ~il was 2 chromatographed on a silica gel column. The product was eluted 3 from the column as a colorless oil ~ith 75:25 hexane/ether. The 4 pro~uct crystallize~ from ether as a ~hite solidO rhe ~elti~g point and elemental analr.~is on the product are tabula~ed in 6 Table D, as co~pou~a No4 D-l.
7Example 14 -- Prepara~ion of 3-(N-3,4-dichloro-8~enzoyl=N-2~6-dimethvl~nylamiaO-qamma-but~rola~t~ne 9A slurry of 12.2 g (0.1 mol~ 2~6-dimethylaniline, ~6~5 10g (0.1 mo}~ alpha-bromo-gamma-butyrolactor.e, 10~6 g (0~1 mol) 11sodium carbonate a~d 150 ml dimethylfor~amide was h2ated at 125-12140~C ~or 21 hours. The reaction mixtu~e was the~ diluted ~ith 13 water and extracted ~ith benzene. ~he ben~ene extr~cts were 14 washed with ~ater, ~ried over magnesium sulfate and evaporated t3 qi~e an oil. The oil was chromatogr~phed on a silica gel ~olumn.
163-(N-2,6-dimethylphenylami~o)-gamma-butyrola~tone, m.p. 85-87c, 17 ~as e~uted from the~olumn ~ith 50:5~ hexane/ether.
t8~ solution of 6.2 g (0.03 ~oll 3-~N-2,6-dimethylphenyl-19ami~o)-gam~a-butyrolacto~e, 6~9 g (0.033 mol) 3~4~dichlorobPnzoyl 20ch'ori~e,:2.S q ~0.033 mol~ p~ridine ana 150 ~1 ethrl a~etate w~s 21stirred over~iqht at 25C and then at 50-75C for 3 hours. Aft2r 22 cooling, the reaction mi~+.ure was washea ~ith water~ diluted with 23 methyl~ne chloride, washed ~ith water, 10% agueous sodium 24 bicarbonate, ~ashed ~i*h water, driea over magnesium sulfate an~
evaporated to qi~e ~ solid residue. The residue ~as crystallizea 26 from ~thyl ether to give ~hs product as a colorless solia. The 27 meltinq point and elemental analysis ~o~ the product is tabulated ~8 in Table D, as compound No. D-2.
29E~ample 15 -- Preparatson of 3-(N-~hloro-30aç~ N-2- eth_~y hen~laminoL_~mma-but~rolactQae 31a slurry of 12.3 g ~0.1 mol~ 2-metho~ya~ e, 16.5 g 32 ~0.1 mol) alpha-bromo-gamma-butyrolactone, 10.6 g (0.1 mol) 3~
1 sodium carb~nate ana 150 ml dimethylformamide ~as stirred at 25~C
2 for 16 hours and then at 90-100C for 6 hours. The reaction 3 mixtur~ ~as diluted with water and sxtracted with benzene. The 4 benzene extra~ts vere wash~d with water, dried o~er magnesium S sulfate and evaporated to gi~e an oilThe oil ~as chromato-6 graphed on a silica gel columnO 3-(N-2-~ethosyphenylaminoj-7 gamma-butyr~lactone was eluted from the colu~n ~ith B0:20 8 hexane/ether.
9 A 5.4 g (û.044 mol) sample of chloroacetyl chl~ride w~s added drop~ise to a solution o~ 9 g (0.~44 ~ol) 3-~N-2-11 methoxyphenylami~o) - gamma-butyrolactone and 3.8 q ~0~ 04B moll 12 pyridine in 150 ml ethyl acetate at 37-46C. ~fter stirring at 13 46C for 15 minutes, the reaction mixtu.e was cooled ana dilute~
14 with water. The organic layer was s~parated, ~ashed with 10 1 S aqueous soaium bicarbonate, ~ashed vith ~ater, dried ov2r 16 magnesium sulfate and evaporated under reduced pressur~ to gi~e 17 the :prOdUC~7 as a c~lorless solid. The melting point and 18 elemental a~al~sis for the product is t~bulated in rable D, as 1 9 co~pouna ~oO D-3.
~xample 16 - Preparation of 1-methyl-3-(N~
21 chloroacet~l-N-2~6~dimethylDhenylamlnoL-qa_t~a-butYrolactam 22 A solu~ion o~ 20OS g ~0~1 mol) 3-(N-2,6-dimethyl-23 phenyl)-ga~ma~butyrDlacto~e, 4.7 ~ (0~15 mol~ methylamine (40%
24 solution in ~ater~ and 200 ml methanol ~as stirred ~ 25~C ~or ~8 hours~ The solven~ was evaporated under reduced pressure tG give 26 an oil resiaue. The residu~ was dissolved in ~ethylene chlori~e, 27 ~ashed with vater, aried over magnesium sulfate and evaporated to 28 ~ive N-methyl-2 (N'-2,6-di~ethylphenylamino~ 4-hydroxybutrramide 29 r ~IV), Ar=2,6-di~6thylphenyl~ R2=H, an~ N - ~=NCH3~o A solutio~ of 1305 g (0.05 mol) phosphorus trib~omide 31 in S ml methylene chloride~was added dropwise at 0C (ice bath~
' .
26 ~
33~
to a solution of 2~.6 g ~0.1 mol) N-methyl-2-(N~-2,6~diaethyl 2 phen~la~i~o) -4-hydr~xybutyramide and 7.9 g (0O 1 mol~ pyridine i~l 3 2û0 ml methylen~ chloride. After 'he additio~ was completed, t~e 4 reaction mixture Yas stirred at 25C for 2 hou~s and at reflux ~o~ 1 hour. The reaction miYture was diluted ~ith ~ater. T~e 6 orqanic layer ~as se pa-ated, washed ~ith water, dried o~er 7 maqnesium sulfate and evaporated to giv~e the crude ~omethyl-2O
B (N9-2,6-di~sthylphenylamino)-4-bromobutrramide ~ (XII), ar=2,6-9 dimethylphenylO R ana R2=H, N ~=NCH3, as a glassy solid The crude bromo-amide was diluted ~ith 150 ml ethanol 11 and reacted ~ith a solution of sodium ethoxide (prspare~ from 5. 6 12 q o~ 43X NaH in mineral oil) in 100 ml rthanol at 25C fmr about 13 16 hours. The rea~tion mixture was e~,raporated, dissolvad in 1~ ~ater and ~iltered. The aqueous filtrate ~as ~ashed with petroleum ether, acidified to pH 1 with 10% hydrochloric acid, 1~ ex~racted wi~h methylene chloride and evaporated to gi~
17 methyl-3-(N-2.!6-dimethylphenylamino~-gamma~butyrola~tamO as an 18 oil~ ~
19 chloroacetyl chloride (1.8 g~ 0.015 mol~ ~as added drop~ise to a stirrPd solution cf 3 ~ (D. 014 mol~ 1-methyl-3- (N-21 2,6-dimethylphenyl~in~)-gam~a-bu~yrola~tam, 1.2 g (0.015 molj 22 pyridine ana 50 ml ethyl acetate. ~he reaction miYture was 23 stlrred at 25C for about 16 hours. The reaction mixture ~as 24 then dilutea with ~ater and ether. The organic layer ~as separa~ed, washed with saturated aqueous sodium bicarbonate, 26 dried over ~aqnesium sulfate and stripp2d to gi~e a~ oil. The 27 oi} was chromatographed on a silica gel column. The product was .: .
'~ 28 eluted from the ~olum~ wi~h etherO The mel~ing point and 29 elemental aQalysis on the produ~t is tabulated in Table Do as co~po~nd ~o. D-4.
~; , ;3 3i~;~
Example 17 ~- Preparation of 1-allyl-~ (N-2 chloroacetxl-N-2L6-dimethylphenylaminoL-qa~ utyr~la 3 A solution of 20. S g (0.1 mol~ 3-~N~2,6-dimethyl-4 phenyl~-gamma-~utyrolactone, 5.9 g (0.1 mol~ allylamine and 200 ml methanol was stirred a~ 2SC for 16 hours and u~der reflux fDr 6 6.5 hours. A~ additio~al 2 g of allylamine ~as then added and 7 heating under reflux continued for 4~ hours. ~he solYe~t was B then evaporated under reduced pressure to qive an oil r_~idue.
~ The residue was chr~matographed on ~ilica gel (ether/petroleum ether elut~o~ to gi~e 21 g of N-allyl-2-~N~-2,6-di~ethyl-11 phenylamino)-4-hrdroxybutyramide ~(XIVl, Ar=2~6-dimethylphenyl, 12 R2-H and N-R-NC8~C~=CH2~-13 A sample of 8.7 g ~0.073 mol) thio~l chloride ~as 14. added drop~ise at 0C ti~ ~ath) to a solution of 17.5 g ~0.067 mol~ N-allyl^2~ 2~6-dimetbylpheny~lami~o)-4-hydroxybutyramide 16 in 250 ml methylene chloride. After the addition was~coapleted~
17 the reac'cion mi~tu~e was stirrea at 25~C for 2 hours ana at .
18 refl~lx until ~s eY~lution ceased ~about 12 nours),. The reac:ti~n 19 mi~ture ~as diluted with 200 ml water. The orgaaic layer ~as ?0 separated"iashed ~ith water, dried over ~agnesium s~l~ate ana 21 evaporat6d ~o qive the crude N~allyl-2~ 2,6-dimethylphenyl-22 amino) -4-chlosobutyramide t (XII~ ~ Ar-2,6-dimethylph~nyl, R ana 23 R2=H ar.d N-R=NCH;!CH=CH2 ~, as an oil.
24 ~he crude chloro-amide was diluted ~ith 250 ml 25 dimethoxyethane and reacted vi~h 3. 2 g of sodium hydr~ de ~5Q~ in 26 mineral oil). The reaction mixture was then stirrad overrlight at 27 about 25C, then filterea through Celit~ and ~ashed ~ h 28 methylene ch}oride. The filtrate was evaporated and 29 chromatographed on silica gel (ether~petroleum ether elutio~
qive 802 g of 1-allyl~3~ 2f6-dimethylpheI;7lami~o)-gamma~
31 butyrolactam, as a~ oil.
'3 i 3~
Chloroacetyl chloride (4.8 g, 0.042 mol) ~as added .
2 drop~ise to a stirr~d solution of 9O 4 g ~0.03~ mol~ 1 ~allyl-3-(N-3 2,6-aimethylphenyla~ino-qamma-butyrolacta~l~ 3.3 g 10.042 mol~
4 pyridine an~ 100 ml ethyl acetaten The reaction mi;xture vas S stirred at 25C for about 16 hours. The reaction mixture was 6 then dilutea ~ith ~ater. The organ~c Ilyer ~as separatedO ~ash~d 7 ~ h sa~urated aqu60us sodium bicarbonate, dried. ove~ magnesium 3 sulfate and strippea to gi~re an oil. The oil was ~hro~atographed 9 on a silica ~el column. The product ~109 g was eluted ~rom the column with ether . ~he ~elting point an d elemental analysis on 11 the product is tabulated in Table D~ as compound No. 22.
12 The compounds tabulated in Tables A, B, C a~d D wEre 13 prepared ~ procedur~s similar to those of Example 1-17. The 14 s~ructure of each c~mpound tabu}ated in Tables A, B, C and D ~as confirmed by nuclear ~agnetic resonanss spectroscopy and~or 16 infrared spectral analysis.
7 ~Eam~le ~8 -=_Preventative_To_ato Late_Bli~ht 18 compounds of the in~ntion were tested ~or the preven~
19 tative control of the Tomato Late Blight organism PhYt~hth~Ea infestans.~ Five- to six-~eek-old to~at~ (cultivar Bo~ny Best) 21 . seedlinqs ~-ere used. Th~ tomato plants were sprayed with a 250-22 ppm suspension of the test compound in ~cetone, ~at~r a~d a small 23 amount of a nonio~ic emulsifler. The sprayed pla~ts vere the~
24 in w ulated ~ne day later with the or~anism, placed in an e~viron-mental charnber and incu~ated a 66-6~F and 100% relative 26 humidit~ for at least 16 hours. Follo~ing the incubation~ the 27 plants ~ere maintained in a greenhouse at 60-80~ relatire 28 hu~idity fcr appro~imate.ly 7 days. The perceut disease cont-ol 29 provided ~y a qiv@n tes~ compound ~as b~ sed on the per~ent disease reduction relatiYe to untreated check plan~s. rhe 31 rPsults are tabulated in Table I and Table IIIo In Ta~les I and II~7 tha test concsntration is 25Q ppm unless other~ise indicated 2 by the figures in parentheses.
3 Ex,am~le_19~ Er__iCant ~Tomat~ ate-Bli~ht~contEol ~
4 Several compounds o~ the invention ~ere tested for the eradicant co~trol of the T~mato Late ~light organism Ph~to~hthoEa 6 n~staas. Fi~e- to si~-w~ek-old to~ato Icultirar Bon~y Bes~) 7 pla~ts ~e~e used. The ~omato plants were inoculated with ~he 8 organism, placed i~ an environmental chamber ana incubated at 1~-9 2~C and 100~ relative humidity for 2 days. ~he plants were then sprayed with a ~50-ppm suspension of the test c~mpound in 11 ac~tons, ~ater and a small amount o~ a nonionic emulsifier. The 12 sprayed plants~w2re allowe~ to dry and then were maintained in a 13 greenhouse at 18-22C and ~t 95-100~ relative humidity. S6ven 14 days after inoculation, th- plants w~ere observed for fungal inf~ctio~s. The a~ount of disease con~rol provided by a gi7e~ -16 test co~pound was based on the a~ount of disease reduc~ion 17 relativ~ to unt~e ted check plants. ~he re~s~lts are tabulated in 18 Table I. In Table I, the test co~centratio~ is 250 ppm unless 19 otherwise indicated by the figures in parentheses.
EEamPl~_20 -- Preventatlv--Grape-DowLy-M lde ContEoa 21 The compounds of the invention s~ere tested for the . _ i 22 control of the grape downy mildew organism PlasmoDara vitlc_aa.
23 Detached leaves, between 70 and 85 mm in diame~er, of 7-week old 24 V is vi~i~era cultivar Emperor grape seedli~gs vere us~d as hosts. The leaves were sprayed ~ith a solution of the tes~ :
26 compoun~ in aceto~e. The sprayed lea~es wer6 aried, in~culatQd 27 - with a spore suspe~sion of the organism, placed in a humid 28 envi~onmental chamber a~d incubated at 1~ 22C and about 100b 29 rela~iv~ `humidity. Seven to nine days af~er inocula~ion, the 30 amount of disease control was determined. The percent disease 31 control pro~ided by a given test compound was based on the ~ .
3~
1 percent disease reduction r~la~ire to untreated check plantsr 2 The results are tabulated in Table I and IVo 3 EXamP~ Eradlant_GEa~_DWn~_Mlld~-W_C_ntr~l 4 The compounds of ~he invention were ~es~ed for the eradica~t control of the grape do~ny mildew organis~ Plasm2~aEa 6 vi~ic_la. Detached leave~ of between 70 and 85 mm di~m~ter of 7-7 week-old Vit1s vin_feEa culti~ar Empèror grape seedlings ve~e 8 ussd as hosts. ~h~ lea qes were i~oculatea with th~ organism and 9 placed in an environme~tal chamber and incubat~d a~ 18-22C a~
at about 100% rela~ive humidity for 1 to 2 days. The leaves were 11 the~ sprayed with a solution of the test compound in acetone.
12 The sprayed leaves ~ere then maintained at 18-22C and a. about 13 100~ rela*ive humidity, Ssven to nine days after inoculation, 14 th~ amount of diseass co~trol ~as ds.termined. ~he percent disease control proYided by a given test compound uas based o~
16 the per~ent dis~ S8 reduction relati~e to nontreated che~k 17 plants. The results :are tabulated in ~able I and Tab}e V. I~
~ .
18 Table I, the;incubation period for all compounds was 2 days.
19 Example 2Z -- Systemic Soil Drench Treatment for Safflower Cro~n and Root ~ot Control 21 Compound ~-4 (4-methoxya~etyl-N-2,6-dimethylphenyl-22 amino-gamma-butyrol~ctone~ was tested to determine its systemic 23 ac~iYity in:soil-dr nch appllcations against the safflo~er crow~
24 and root rot organisms, Phyto~hthoEa crYPto~ea and P. ~E_sitica,.
Two-ueek-ola safflower seedlings were used as hosts.
26 Pots containing ths seedlings ~ere drenched with an ~u~ous 27 suspension o~ the test compound at ~arious test co~ce~trations 28 ~four pots per c~ncsn'cration le~el)~ One day after tre~tment a 29 spall~ of the organism ~as poured on the soil surface in the potsD
~h~ spaw~ was prepared b~ culti~ating the orga~ism in ~ mixture 31 of oat ~lakes, potato dextrose and soil~ The inoculate~
- 3~ -~33~
seedlings vere then maintained in a greenhouse at 20-25~C day and 2 15-20C night ~emp~rature. Three to four weeks after 3 inoculation, the plant roots and cro~n were rated for disease.
4 Th~ parcent diseas control provided by the t~st compound was based on percent disease r~duction relative to non-tr~ated check 6 plants. The test concentr~ tions and the perce~t diseas~ control are tabulated in Table II.
8 Ex m~le 23 -- Tomato Ea 1 2li~hl 9 Compounds of the invention were tested for the control -of the Tomato Early Blight organis~, Alterna~ia solani. Tomato 11 (cultiYar ~onny Best) seedlings of 6 to 7 weeks old ~era used.
12 Ths tomato plants vere sprayed ~ith a 250-ppm solutio~ of the 13 test compound in an acetone-and-water solution ~ontaining a small 14 amount of a non-io~ic emulsifier. The sprayed plants ~re inoculated one day later with the orga~ism, placed in an 16 anvironaental chamber, incubated at 66-68F in 100~ relative 17 humidity ~or 2 days, and ~hen maintained in a greenhousa a~ 66-18 68F for S days. Percant disease co~trol ~as based on the 19 percent disease deveIopment on u~treated ch~ck plants. The compou~ds found to be efectiYe at the test co~centrations and 21 th~ results are tabulated in Tahle III.
22 Exa_ple 24~ cel~rr-Late-Bliqht 23 Compounds of the invention ~ere tested for th co~trol 24 of Celery Late Bligh. ~sing celery (culti~ar Utah) plants 11 weeks old. The Celerg Late Blight organism was SePtorl- aPi .
26 The celery plants ~ere spr~ed ~ith solutions of the candidate 27 to~ica~t mixed with ~cetona, ~ater and a nonionic emulsifier.
28 . The plan ~ wsre then inoculated ~ith the organism and placed in 29 an enviro~mental chambe~ and incubated a~ 66~68P in 100~
~elati~e humidity for an extanded period of ti~a (approxima~ely 31 2~ hours~. Follo~ing the in~u~ation, the plants were maintained ~. .
3~
1 at a 60-80~ relative hu~idity in a gree~house for appro~imately 2 14 days. ~he percent disease control provided by a givQn 3 candidate toxicant is based on ~h~ percent ~ise3se redu~,tio~
4 relative to untrea~ed check plants. ~he compounds founa to be S effective at thQ test concentrations and tha r~sults ar 6 tabulated in Tabl6 III.
7 Exam~le_25~- ~otEytis_cinerea_c_ntrol 8 Compounds o f the inventio:c ~ere tested for BotEyti s 9 ci_erea control usi~g deta-hed, vell-developed pri~ary leaves of ~
a 4-6 week O~a horsebean plant. The leaves ~ere dipped into a 11 40-ppm solution Df the test compound in acetone and vat3r 12 containing a s~all amount of a nonionic emulsifier, then taken 13 out and placed in a petri plate lined ~ith two pieces of filter 14 paper. The lea~es ~ere allo~ed to dFy ~hile the filter paper ~as kept moist by addi~g wa~er as required. Th~ treated le~ ves were 16 then in~culated ~ith the spores of Botrxtls c neEea fungus ~rown 17 on :potato de~trose agar pl~tes.~ The plate was covared after 1B iaoculation and kept at 23. 5QC. The fi}ter-paper li~ing o~ the 19 plate ~as kept saturated ~ith ~at~r throu~hout the test. The rats of disease incidsnce was determined in 3 to ~ days, Yhen the 21 diseasa symptoms w~re ~ully evident on non-treated chsck leaYes.
22 The percentage disaa~e control provided by the test compound ~as 23 calculated as-the percentage disease reduction base~ on the non-24 treated check leavss. The compounds found to be e~fective at the test concentration and the results are tabulatea i~ ~able III.
26 ~xample_2~ Po~dery_~lld~
27 The po~dery mildew test was mada using bean seedlings 28 (cultivar Bountifulj ~ith ~ell-developed pri~ary lea~es~ The 29 pathogen ~as EE~i~he Doly~oni~ Tbe bean seedlings were spraysd Yith a 250-ppm solution of the test compou~d i~ an acetone~ater 31 ~i~tur~ containing a ~onio~ic emulsifier. ~he treated pla~ts ~ .
33~
were inoculated one day after spray application of the test 2 co~pound ~rith the p~thogen~ The plants ~ere then maintained in a 3 greenhouse at a 60-80~ r~l~ tive hu~idity and at a temperature of 4 68-70F~ ~hs rate of in~e~tion on the leaves ~as made after about 10 day~. The p6rcent disease control pro~ided by a give~
6 test compound ~as based on the disease reduction relative to 7 untreated check plants~ The compounds found to be effective at 8 the test concentrations and the results are tabulated in Table 9 III. The compounds found to be e~fective at the test concen- ~
10 trations and the results are tabulated in ~able II.
11 Exam~le 27 -- Fermentat~on Tect 12 An in-vitro test was carried out to determine the 13 influence of 3-(N-chloroacetyl-N-2,6-dimethvlphenylamin~)-gamma-14 butyrolactone ~Compou~d D-8) on yeas.ts responsible for the " ~ , 15 alcobolic fer-entation of grapes~ The test ~as condueted as ; 16 follo~s:
17 Erlenmeyer flasks ~S00 cc) vere ~filled with 200 cc~of 18 gra~pe juice~ (density 1O07 ~cc) extracted from bunc:hes of :: :
19 ~ ~ad~le ~ Anaevia~ grapest :The test compound was added to the grape juice and the extent of fermentation determined by 21 measuring the cuMulative loss of ~eight due to carbon dioxide 2~ escape. For comparison, the test ~as conducted with a~ untreated 23 chec~ a~d a commercial fungicide~ The concentration of test 24 compound and the results for the first 8 days of ~erme~tation ar~
2S tabulated iD Table rI.
33~
TABLE Vl: - :
F~Ementation Test 3 Cumulative loss of weight (in grams) 4 Product Conc. __ ___ __due_to_02_eSca~e_af_~r~
_add~d_ _~Pm_ l_d~y 2_days 3_days 4_days 7_daYs 8_d~s 6Comp. ~-8 1 0~9 5O010.5 11.3 14.2 14.5 7 2 0.8 5.210.4 11.1 13,4 13.7 8 4 1,0 5.210.~ 11.1 13.1 13.3 9 B loO 5~411~0 11~8 14~5 15~2 10Commercial 1 0.4 0.52.8 3.6 8.~ 10.1 llFungicide 2 0.~ 0.41.3 1.8 4.7 5.6 12 4 0.4 0.40~7 0.8 2.1 3~1 -13 8 0.3 0.40.7 0.7 1.2 1.5 14 None - 0.9 5.411.1 11~6 14.2 14~5 1S ~xa Ple_28__- Eradlcant Down~_Nmldew EQ~trol 16 3~ chloroacetyl N-2,6-dimethylphenylamino~-gamm~-17 butyrolactone (compound D-8) a~d s2Yeral com2ercial fun~icides 18 were tested for the eradicant control o~ do~ny mil~6s~ (PlasmoPaEa 19 riticola OD grape leaves. The commercial fungi~idss employ~d 2 0 w er e ~
2~ Captafol -- cis-N-(1rl,2,2-tetrachloroet~ylthio)-4- ..
22 cyclohexe~e :1,2-dicarbosimide 23 Pentinac`eta~e -- triphenyltin acetate ~4 Chl~othalonil -- 2,4,5,6-tetrachloroisophthalo~itrile 2~ Cupric sulfate :l :
26 Detached leav~s of Carignane and Er~peror grape pl~ nts 27 ~er~ us~d as hosts. The leaves were inoculated ~ith tha organism 28 and placed in an environment chamber and incubated at 18-22C and 29 at ~about 100% relative humidity for 1 to 3 days (1 to 2 days ~or 30 Emperor leaves, 3: days ~or Carigna~e ~eaves) . The leaYes ~ re 31 then sprayed ~ith a solution of the test compound in ac~tone.
32 ~he sprayed leaves were then maintained at 18-22C an~ at abDut 33 .. 100~ relative hum:idity. Eight to nine days after inoculation,
33~
A 2.4-q (0 .021 mol) sampl~ ~f chloroacetyl chlDridQ ~s 2 added to a refluxing solu~ion o 5.0 g (0.021 mol~ 3-(N-2-methyl-3 naphth-l-ylamino)-qamma-butyrolactone in 100 ml tolue~e. The 4 reaction mixture was heated under reflux for 30 minutes. Gas ~lS
5 evolved and a ~hite precipitate formed ~uring the 30~mi~ute 6 reflux period. The reaction mixture was coQled, washed ~ith 7 ~at~r, ~ied o~er m3gnesium sulfate and evaporated under reducea 8 pressure to give 4.3 g of p~oduc~, as a white solid, m.p. 121 9 122Co The irlfrared spectrum of the pr~duct sho~ed t~o stro 10 carb~yl abs~rptio~ bands at 5. 62 micror.s and S. 8B ~icrons. Th~
11 proauct is tabulated in Table C as Co~pound No,. C~1r 12 Example 10 -~- Prep~ratior. of 3-[N-methoxymethyl-13 N-2-m_thYlnaP-th~ a~i~noL-aa~ma-bu~yro~ tOne 14 A 2. 4 g ~0 . 022 ~ol) sample of methoxyacetyl chloride lS ~as added drop~ise to a solu~ion of '5.5 g (0.022 mol) 3-~N-2-16 methylnaph~h-1-ylamino~-gamma-butyr~7acto~e and: 107 g (OoQ22 mol~
17 pyridine in 100 ml aichlorome~harle. Th~ reaction ~i~ture w~s :: .
~-~: 18 stirred one ~hour at about 25G and the~ heated under reflu~z for 6 19 hours . After ~ooli~ g o~ernight, the re~ction mixture ~as ~ashea I
suc~essively with water, saturated sodium hicarbonate solution, 21 water9 dried o~er magnesium sulfat~ and e~aporatsd u~der reduce~
22 pressure. ~he resiaue was chromatographed through ~ silica gel 23 column. Elution with 25% acetone/75~ petroleum ether g~ve 4.3 3 .
24 of the produ~t, m.p. 42-46C. The product is tabulated in ~a})le 25 C as Compound Ito. ~-2.
26 Example 11 ~- Preparation of 3~ (N-chloroacetylo 27 N=2L6-_ methYlE!heaQlaminL-qamma-bUtX~laCt~e 28 a solution of 410 g ~2 mols) N-2,6~di~ethy}phany}amin~-2g gamma bu~yr~lacton~, mOp., 85~86.5C, ana 197.5 g (2, 5 m~ls) 30 pyridine i~ 2 li~ers be~zene s~as heated o re~lux. To the 31 sDlut~ on was added arop~dise ~60 g (2. 3 E~ols) chloro~cetyl 32 ~hloride over a 40-minute period. The reaction mixt ure ~as 33~
1 heated under reflux for 20 additional minutes/ cooled and 2 filtered to remove a precipi~a~e of pyridine hydr~chloride. The 3 filtrate ~2s washed ~ith ~ater, dried over magnesiu~ sulfats and 4 evaporated u~der reduced pressure to g~ve a colorless white 5 solid. The solid was slurried ~ith isopropanol, ~iltered~ and 6 dried to give S01 g of product, as a colorless 501i~, m. p. 145. 5-7 1 47~ .
8 The produ-t has an oral LD5n (rats~ of >1000 mg~kg a~d 9 derl~al LD~o (~ats~ ~f >2000 mgfkg. The product is tabulatea in Table D as _ompoun~ No. D-8~
11 Example 12 -- Preparation of 3-~N-chloroacetyl-12 N-2~6-~ methrlehenvlaminoL-s-mgth~l-aamma-but~rol~-toBe : 13 a 500 ml round-bottom flask eguipped with a t~D-way 14 stopcoc~ was cbarged ~ith 24~2 g (0~2 mol) 2,6-dimethyla~iline and 19. 0 q ~0.106 ~lj alpha-bromo gamma-~alerolactone. The 16 flask was evac~ate~ to 20 mm of Hg, then slovly heated to 100C
17 ~hile perioaically eYacuating *he flask by means of a w~ter- - :
18 aspirator t~ ~aint~in the pressure at about 17-40 mm o~ Hg.
19 After hea~lng th~ reaction mixture at about 100~C and at 17-40 ~m o}~q ~or ~2 h~ursj the reaction mixtur~ ~a-Q cooled and dilutea 21 with 300 ml ethyl ether. A solid precipitate of 2,6-dimethyl~
22 aniline hydrobromide salt ~as removed by filtration. ~he 2~ filtra~e was ~ashed with 5% aqueous hydrochl~ric acid solution, 24 ~ater, dried over ~agnesium sulfate and evaporated under red~ce~
pressur~ to:gi~e 19.2 g of 3~ 2,6-dim~thylphenylami~o~-5-26 methyl-gamma-but~solactone, as a viscous oilO
27 a 10. 9-g ~Q.096-mol) sample of chloroacetyl chloride 28 ~as added slo~l~ to a solution of 19.2 ~ (0.088 mol) 3-(N-2,6- ;
29 di~ethylphsnylaminD) -5-me*hyl-gamma-butyrolactone and 7.6 g (0O 096 mol) p7ridifle in 250 ml ethyl acetate. A~ exother~ ensued 31 and a precipitat~ separated. After stirring for 16 hours at ' , ~3L33~
.
about 20C, the rea~tion mixture was washed ~ith uater, vashed 2 uith saturated aqueous soaium bicarbonate solution, washed ~ith 3 uater, dried over magnesium sulfate and evaporated under reduce~
4 pressure to give a thick oil which crystallized from ethyl ether to qi~e a qellou solid. ~hs yellow solid was ~ashe~ vith cold 6 ethyl ether~petroleum ether and air-dri~d to give 15.8 g of 3-~N-7 chloroacetyl-N-2,6~ ethylphenylamino~-5-methyl-gamma^
8 butyrolactone, m.p. 128-131C. The pr~uct is ta~ulated in ~able 9 D as Compound No~ ~-14.
lQ E~ample 13 -- Prepara~ion of 3-~N-propionyl-~ 3~4-d chloro~henylam-nQL-~amma-butxrolacto~Q
12 A reaction flask was charg6d with 32~4 g (0.2 mol) of 13 3,4-dichloroaniline and 16. 5 g tO. 1 ~ol alpha-bro~o-gamma 14 butyrolactone. The f}ask was eYacuated to 20 ~m of Hg ~nd then lS slo~ly hea~ed to 110-14~C. ~he r~action pressure increased to 16 88 mm of Hq, Aftar maintaining at about 23 mm of Hg and 120C .
1i for 1 hour,: the rea~,tion mixture ~as co~led to give a ~olid 18 m}~ture of 3~4-dichloroanillne hyd~robro~id0 sall: and~ 3-(N-3, 4-19 aichlorophe~ylamino)-ga~ma butyrolactoneO The ~ixture ~as treated with ma~h71en~ chloride ~and filt~red. The filtrate ~as 21 evaporated to give the lactone product ~X), Ar=3,4-dichlor-22 phenyl, R and ~Z=H~ and Y=O ].
23 A solutl~n of 5~9 g ~0.~24 ~ol) 3-(N-3~4-dichloro~
24 phenylamino)-gamma-butyrolactone, 2.1 g ~0.026 mol) pyridi~e ang 2~4 g ~0.026 mol) propionyl chloride in 110 ml ethyl acetate ~as 26 heated at 45C. ~fter 1/2 hour at 453C, thin-layer 27 chromatoqraphic analysis showed substantial amoun~s of the . 28 lactone reaclant. Another 2.1 g pyridi~e and 2. 4 9 propionyl : 29 chloride Yere added to ~he reaction mixture. ~he reaction ~ixture ~as ~hen he~ted at refLux for 1/2 hour, cooled, pashed 31 with water, 10~ aqueous sodium bicarbon~te, vater; dried o~er .:
~ - 2~ - .
- .
3 3~
1 magnesium sulfate and evaporated to give an oil. The ~il was 2 chromatographed on a silica gel column. The product was eluted 3 from the column as a colorless oil ~ith 75:25 hexane/ether. The 4 pro~uct crystallize~ from ether as a ~hite solidO rhe ~elti~g point and elemental analr.~is on the product are tabula~ed in 6 Table D, as co~pou~a No4 D-l.
7Example 14 -- Prepara~ion of 3-(N-3,4-dichloro-8~enzoyl=N-2~6-dimethvl~nylamiaO-qamma-but~rola~t~ne 9A slurry of 12.2 g (0.1 mol~ 2~6-dimethylaniline, ~6~5 10g (0.1 mo}~ alpha-bromo-gamma-butyrolactor.e, 10~6 g (0~1 mol) 11sodium carbonate a~d 150 ml dimethylfor~amide was h2ated at 125-12140~C ~or 21 hours. The reaction mixtu~e was the~ diluted ~ith 13 water and extracted ~ith benzene. ~he ben~ene extr~cts were 14 washed with ~ater, ~ried over magnesium sulfate and evaporated t3 qi~e an oil. The oil was chromatogr~phed on a silica gel ~olumn.
163-(N-2,6-dimethylphenylami~o)-gamma-butyrola~tone, m.p. 85-87c, 17 ~as e~uted from the~olumn ~ith 50:5~ hexane/ether.
t8~ solution of 6.2 g (0.03 ~oll 3-~N-2,6-dimethylphenyl-19ami~o)-gam~a-butyrolacto~e, 6~9 g (0.033 mol) 3~4~dichlorobPnzoyl 20ch'ori~e,:2.S q ~0.033 mol~ p~ridine ana 150 ~1 ethrl a~etate w~s 21stirred over~iqht at 25C and then at 50-75C for 3 hours. Aft2r 22 cooling, the reaction mi~+.ure was washea ~ith water~ diluted with 23 methyl~ne chloride, washed ~ith water, 10% agueous sodium 24 bicarbonate, ~ashed ~i*h water, driea over magnesium sulfate an~
evaporated to qi~e ~ solid residue. The residue ~as crystallizea 26 from ~thyl ether to give ~hs product as a colorless solia. The 27 meltinq point and elemental analysis ~o~ the product is tabulated ~8 in Table D, as compound No. D-2.
29E~ample 15 -- Preparatson of 3-(N-~hloro-30aç~ N-2- eth_~y hen~laminoL_~mma-but~rolactQae 31a slurry of 12.3 g ~0.1 mol~ 2-metho~ya~ e, 16.5 g 32 ~0.1 mol) alpha-bromo-gamma-butyrolactone, 10.6 g (0.1 mol) 3~
1 sodium carb~nate ana 150 ml dimethylformamide ~as stirred at 25~C
2 for 16 hours and then at 90-100C for 6 hours. The reaction 3 mixtur~ ~as diluted with water and sxtracted with benzene. The 4 benzene extra~ts vere wash~d with water, dried o~er magnesium S sulfate and evaporated to gi~e an oilThe oil ~as chromato-6 graphed on a silica gel columnO 3-(N-2-~ethosyphenylaminoj-7 gamma-butyr~lactone was eluted from the colu~n ~ith B0:20 8 hexane/ether.
9 A 5.4 g (û.044 mol) sample of chloroacetyl chl~ride w~s added drop~ise to a solution o~ 9 g (0.~44 ~ol) 3-~N-2-11 methoxyphenylami~o) - gamma-butyrolactone and 3.8 q ~0~ 04B moll 12 pyridine in 150 ml ethyl acetate at 37-46C. ~fter stirring at 13 46C for 15 minutes, the reaction mixtu.e was cooled ana dilute~
14 with water. The organic layer was s~parated, ~ashed with 10 1 S aqueous soaium bicarbonate, ~ashed vith ~ater, dried ov2r 16 magnesium sulfate and evaporated under reduced pressur~ to gi~e 17 the :prOdUC~7 as a c~lorless solid. The melting point and 18 elemental a~al~sis for the product is t~bulated in rable D, as 1 9 co~pouna ~oO D-3.
~xample 16 - Preparation of 1-methyl-3-(N~
21 chloroacet~l-N-2~6~dimethylDhenylamlnoL-qa_t~a-butYrolactam 22 A solu~ion o~ 20OS g ~0~1 mol) 3-(N-2,6-dimethyl-23 phenyl)-ga~ma~butyrDlacto~e, 4.7 ~ (0~15 mol~ methylamine (40%
24 solution in ~ater~ and 200 ml methanol ~as stirred ~ 25~C ~or ~8 hours~ The solven~ was evaporated under reduced pressure tG give 26 an oil resiaue. The residu~ was dissolved in ~ethylene chlori~e, 27 ~ashed with vater, aried over magnesium sulfate and evaporated to 28 ~ive N-methyl-2 (N'-2,6-di~ethylphenylamino~ 4-hydroxybutrramide 29 r ~IV), Ar=2,6-di~6thylphenyl~ R2=H, an~ N - ~=NCH3~o A solutio~ of 1305 g (0.05 mol) phosphorus trib~omide 31 in S ml methylene chloride~was added dropwise at 0C (ice bath~
' .
26 ~
33~
to a solution of 2~.6 g ~0.1 mol) N-methyl-2-(N~-2,6~diaethyl 2 phen~la~i~o) -4-hydr~xybutyramide and 7.9 g (0O 1 mol~ pyridine i~l 3 2û0 ml methylen~ chloride. After 'he additio~ was completed, t~e 4 reaction mixture Yas stirred at 25C for 2 hou~s and at reflux ~o~ 1 hour. The reaction miYture was diluted ~ith ~ater. T~e 6 orqanic layer ~as se pa-ated, washed ~ith water, dried o~er 7 maqnesium sulfate and evaporated to giv~e the crude ~omethyl-2O
B (N9-2,6-di~sthylphenylamino)-4-bromobutrramide ~ (XII), ar=2,6-9 dimethylphenylO R ana R2=H, N ~=NCH3, as a glassy solid The crude bromo-amide was diluted ~ith 150 ml ethanol 11 and reacted ~ith a solution of sodium ethoxide (prspare~ from 5. 6 12 q o~ 43X NaH in mineral oil) in 100 ml rthanol at 25C fmr about 13 16 hours. The rea~tion mixture was e~,raporated, dissolvad in 1~ ~ater and ~iltered. The aqueous filtrate ~as ~ashed with petroleum ether, acidified to pH 1 with 10% hydrochloric acid, 1~ ex~racted wi~h methylene chloride and evaporated to gi~
17 methyl-3-(N-2.!6-dimethylphenylamino~-gamma~butyrola~tamO as an 18 oil~ ~
19 chloroacetyl chloride (1.8 g~ 0.015 mol~ ~as added drop~ise to a stirrPd solution cf 3 ~ (D. 014 mol~ 1-methyl-3- (N-21 2,6-dimethylphenyl~in~)-gam~a-bu~yrola~tam, 1.2 g (0.015 molj 22 pyridine ana 50 ml ethyl acetate. ~he reaction miYture was 23 stlrred at 25C for about 16 hours. The reaction mixture ~as 24 then dilutea with ~ater and ether. The organic layer ~as separa~ed, washed with saturated aqueous sodium bicarbonate, 26 dried over ~aqnesium sulfate and stripp2d to gi~e a~ oil. The 27 oi} was chromatographed on a silica gel column. The product was .: .
'~ 28 eluted from the ~olum~ wi~h etherO The mel~ing point and 29 elemental aQalysis on the produ~t is tabulated in Table Do as co~po~nd ~o. D-4.
~; , ;3 3i~;~
Example 17 ~- Preparation of 1-allyl-~ (N-2 chloroacetxl-N-2L6-dimethylphenylaminoL-qa~ utyr~la 3 A solution of 20. S g (0.1 mol~ 3-~N~2,6-dimethyl-4 phenyl~-gamma-~utyrolactone, 5.9 g (0.1 mol~ allylamine and 200 ml methanol was stirred a~ 2SC for 16 hours and u~der reflux fDr 6 6.5 hours. A~ additio~al 2 g of allylamine ~as then added and 7 heating under reflux continued for 4~ hours. ~he solYe~t was B then evaporated under reduced pressure to qive an oil r_~idue.
~ The residue was chr~matographed on ~ilica gel (ether/petroleum ether elut~o~ to gi~e 21 g of N-allyl-2-~N~-2,6-di~ethyl-11 phenylamino)-4-hrdroxybutyramide ~(XIVl, Ar=2~6-dimethylphenyl, 12 R2-H and N-R-NC8~C~=CH2~-13 A sample of 8.7 g ~0.073 mol) thio~l chloride ~as 14. added drop~ise at 0C ti~ ~ath) to a solution of 17.5 g ~0.067 mol~ N-allyl^2~ 2~6-dimetbylpheny~lami~o)-4-hydroxybutyramide 16 in 250 ml methylene chloride. After the addition was~coapleted~
17 the reac'cion mi~tu~e was stirrea at 25~C for 2 hours ana at .
18 refl~lx until ~s eY~lution ceased ~about 12 nours),. The reac:ti~n 19 mi~ture ~as diluted with 200 ml water. The orgaaic layer ~as ?0 separated"iashed ~ith water, dried over ~agnesium s~l~ate ana 21 evaporat6d ~o qive the crude N~allyl-2~ 2,6-dimethylphenyl-22 amino) -4-chlosobutyramide t (XII~ ~ Ar-2,6-dimethylph~nyl, R ana 23 R2=H ar.d N-R=NCH;!CH=CH2 ~, as an oil.
24 ~he crude chloro-amide was diluted ~ith 250 ml 25 dimethoxyethane and reacted vi~h 3. 2 g of sodium hydr~ de ~5Q~ in 26 mineral oil). The reaction mixture was then stirrad overrlight at 27 about 25C, then filterea through Celit~ and ~ashed ~ h 28 methylene ch}oride. The filtrate was evaporated and 29 chromatographed on silica gel (ether~petroleum ether elutio~
qive 802 g of 1-allyl~3~ 2f6-dimethylpheI;7lami~o)-gamma~
31 butyrolactam, as a~ oil.
'3 i 3~
Chloroacetyl chloride (4.8 g, 0.042 mol) ~as added .
2 drop~ise to a stirr~d solution of 9O 4 g ~0.03~ mol~ 1 ~allyl-3-(N-3 2,6-aimethylphenyla~ino-qamma-butyrolacta~l~ 3.3 g 10.042 mol~
4 pyridine an~ 100 ml ethyl acetaten The reaction mi;xture vas S stirred at 25C for about 16 hours. The reaction mixture was 6 then dilutea ~ith ~ater. The organ~c Ilyer ~as separatedO ~ash~d 7 ~ h sa~urated aqu60us sodium bicarbonate, dried. ove~ magnesium 3 sulfate and strippea to gi~re an oil. The oil was ~hro~atographed 9 on a silica ~el column. The product ~109 g was eluted ~rom the column with ether . ~he ~elting point an d elemental analysis on 11 the product is tabulated in Table D~ as compound No. 22.
12 The compounds tabulated in Tables A, B, C a~d D wEre 13 prepared ~ procedur~s similar to those of Example 1-17. The 14 s~ructure of each c~mpound tabu}ated in Tables A, B, C and D ~as confirmed by nuclear ~agnetic resonanss spectroscopy and~or 16 infrared spectral analysis.
7 ~Eam~le ~8 -=_Preventative_To_ato Late_Bli~ht 18 compounds of the in~ntion were tested ~or the preven~
19 tative control of the Tomato Late Blight organism PhYt~hth~Ea infestans.~ Five- to six-~eek-old to~at~ (cultivar Bo~ny Best) 21 . seedlinqs ~-ere used. Th~ tomato plants were sprayed with a 250-22 ppm suspension of the test compound in ~cetone, ~at~r a~d a small 23 amount of a nonio~ic emulsifler. The sprayed pla~ts vere the~
24 in w ulated ~ne day later with the or~anism, placed in an e~viron-mental charnber and incu~ated a 66-6~F and 100% relative 26 humidit~ for at least 16 hours. Follo~ing the incubation~ the 27 plants ~ere maintained in a greenhouse at 60-80~ relatire 28 hu~idity fcr appro~imate.ly 7 days. The perceut disease cont-ol 29 provided ~y a qiv@n tes~ compound ~as b~ sed on the per~ent disease reduction relatiYe to untreated check plan~s. rhe 31 rPsults are tabulated in Table I and Table IIIo In Ta~les I and II~7 tha test concsntration is 25Q ppm unless other~ise indicated 2 by the figures in parentheses.
3 Ex,am~le_19~ Er__iCant ~Tomat~ ate-Bli~ht~contEol ~
4 Several compounds o~ the invention ~ere tested for the eradicant co~trol of the T~mato Late ~light organism Ph~to~hthoEa 6 n~staas. Fi~e- to si~-w~ek-old to~ato Icultirar Bon~y Bes~) 7 pla~ts ~e~e used. The ~omato plants were inoculated with ~he 8 organism, placed i~ an environmental chamber ana incubated at 1~-9 2~C and 100~ relative humidity for 2 days. ~he plants were then sprayed with a ~50-ppm suspension of the test c~mpound in 11 ac~tons, ~ater and a small amount o~ a nonionic emulsifier. The 12 sprayed plants~w2re allowe~ to dry and then were maintained in a 13 greenhouse at 18-22C and ~t 95-100~ relative humidity. S6ven 14 days after inoculation, th- plants w~ere observed for fungal inf~ctio~s. The a~ount of disease con~rol provided by a gi7e~ -16 test co~pound was based on the a~ount of disease reduc~ion 17 relativ~ to unt~e ted check plants. ~he re~s~lts are tabulated in 18 Table I. In Table I, the test co~centratio~ is 250 ppm unless 19 otherwise indicated by the figures in parentheses.
EEamPl~_20 -- Preventatlv--Grape-DowLy-M lde ContEoa 21 The compounds of the invention s~ere tested for the . _ i 22 control of the grape downy mildew organism PlasmoDara vitlc_aa.
23 Detached leaves, between 70 and 85 mm in diame~er, of 7-week old 24 V is vi~i~era cultivar Emperor grape seedli~gs vere us~d as hosts. The leaves were sprayed ~ith a solution of the tes~ :
26 compoun~ in aceto~e. The sprayed lea~es wer6 aried, in~culatQd 27 - with a spore suspe~sion of the organism, placed in a humid 28 envi~onmental chamber a~d incubated at 1~ 22C and about 100b 29 rela~iv~ `humidity. Seven to nine days af~er inocula~ion, the 30 amount of disease control was determined. The percent disease 31 control pro~ided by a given test compound was based on the ~ .
3~
1 percent disease reduction r~la~ire to untreated check plantsr 2 The results are tabulated in Table I and IVo 3 EXamP~ Eradlant_GEa~_DWn~_Mlld~-W_C_ntr~l 4 The compounds of ~he invention were ~es~ed for the eradica~t control of the grape do~ny mildew organis~ Plasm2~aEa 6 vi~ic_la. Detached leave~ of between 70 and 85 mm di~m~ter of 7-7 week-old Vit1s vin_feEa culti~ar Empèror grape seedlings ve~e 8 ussd as hosts. ~h~ lea qes were i~oculatea with th~ organism and 9 placed in an environme~tal chamber and incubat~d a~ 18-22C a~
at about 100% rela~ive humidity for 1 to 2 days. The leaves were 11 the~ sprayed with a solution of the test compound in acetone.
12 The sprayed leaves ~ere then maintained at 18-22C and a. about 13 100~ rela*ive humidity, Ssven to nine days after inoculation, 14 th~ amount of diseass co~trol ~as ds.termined. ~he percent disease control proYided by a given test compound uas based o~
16 the per~ent dis~ S8 reduction relati~e to nontreated che~k 17 plants. The results :are tabulated in ~able I and Tab}e V. I~
~ .
18 Table I, the;incubation period for all compounds was 2 days.
19 Example 2Z -- Systemic Soil Drench Treatment for Safflower Cro~n and Root ~ot Control 21 Compound ~-4 (4-methoxya~etyl-N-2,6-dimethylphenyl-22 amino-gamma-butyrol~ctone~ was tested to determine its systemic 23 ac~iYity in:soil-dr nch appllcations against the safflo~er crow~
24 and root rot organisms, Phyto~hthoEa crYPto~ea and P. ~E_sitica,.
Two-ueek-ola safflower seedlings were used as hosts.
26 Pots containing ths seedlings ~ere drenched with an ~u~ous 27 suspension o~ the test compound at ~arious test co~ce~trations 28 ~four pots per c~ncsn'cration le~el)~ One day after tre~tment a 29 spall~ of the organism ~as poured on the soil surface in the potsD
~h~ spaw~ was prepared b~ culti~ating the orga~ism in ~ mixture 31 of oat ~lakes, potato dextrose and soil~ The inoculate~
- 3~ -~33~
seedlings vere then maintained in a greenhouse at 20-25~C day and 2 15-20C night ~emp~rature. Three to four weeks after 3 inoculation, the plant roots and cro~n were rated for disease.
4 Th~ parcent diseas control provided by the t~st compound was based on percent disease r~duction relative to non-tr~ated check 6 plants. The test concentr~ tions and the perce~t diseas~ control are tabulated in Table II.
8 Ex m~le 23 -- Tomato Ea 1 2li~hl 9 Compounds of the invention were tested for the control -of the Tomato Early Blight organis~, Alterna~ia solani. Tomato 11 (cultiYar ~onny Best) seedlings of 6 to 7 weeks old ~era used.
12 Ths tomato plants vere sprayed ~ith a 250-ppm solutio~ of the 13 test compound in an acetone-and-water solution ~ontaining a small 14 amount of a non-io~ic emulsifier. The sprayed plants ~re inoculated one day later with the orga~ism, placed in an 16 anvironaental chamber, incubated at 66-68F in 100~ relative 17 humidity ~or 2 days, and ~hen maintained in a greenhousa a~ 66-18 68F for S days. Percant disease co~trol ~as based on the 19 percent disease deveIopment on u~treated ch~ck plants. The compou~ds found to be efectiYe at the test co~centrations and 21 th~ results are tabulated in Tahle III.
22 Exa_ple 24~ cel~rr-Late-Bliqht 23 Compounds of the invention ~ere tested for th co~trol 24 of Celery Late Bligh. ~sing celery (culti~ar Utah) plants 11 weeks old. The Celerg Late Blight organism was SePtorl- aPi .
26 The celery plants ~ere spr~ed ~ith solutions of the candidate 27 to~ica~t mixed with ~cetona, ~ater and a nonionic emulsifier.
28 . The plan ~ wsre then inoculated ~ith the organism and placed in 29 an enviro~mental chambe~ and incubated a~ 66~68P in 100~
~elati~e humidity for an extanded period of ti~a (approxima~ely 31 2~ hours~. Follo~ing the in~u~ation, the plants were maintained ~. .
3~
1 at a 60-80~ relative hu~idity in a gree~house for appro~imately 2 14 days. ~he percent disease control provided by a givQn 3 candidate toxicant is based on ~h~ percent ~ise3se redu~,tio~
4 relative to untrea~ed check plants. ~he compounds founa to be S effective at thQ test concentrations and tha r~sults ar 6 tabulated in Tabl6 III.
7 Exam~le_25~- ~otEytis_cinerea_c_ntrol 8 Compounds o f the inventio:c ~ere tested for BotEyti s 9 ci_erea control usi~g deta-hed, vell-developed pri~ary leaves of ~
a 4-6 week O~a horsebean plant. The leaves ~ere dipped into a 11 40-ppm solution Df the test compound in acetone and vat3r 12 containing a s~all amount of a nonionic emulsifier, then taken 13 out and placed in a petri plate lined ~ith two pieces of filter 14 paper. The lea~es ~ere allo~ed to dFy ~hile the filter paper ~as kept moist by addi~g wa~er as required. Th~ treated le~ ves were 16 then in~culated ~ith the spores of Botrxtls c neEea fungus ~rown 17 on :potato de~trose agar pl~tes.~ The plate was covared after 1B iaoculation and kept at 23. 5QC. The fi}ter-paper li~ing o~ the 19 plate ~as kept saturated ~ith ~at~r throu~hout the test. The rats of disease incidsnce was determined in 3 to ~ days, Yhen the 21 diseasa symptoms w~re ~ully evident on non-treated chsck leaYes.
22 The percentage disaa~e control provided by the test compound ~as 23 calculated as-the percentage disease reduction base~ on the non-24 treated check leavss. The compounds found to be e~fective at the test concentration and the results are tabulatea i~ ~able III.
26 ~xample_2~ Po~dery_~lld~
27 The po~dery mildew test was mada using bean seedlings 28 (cultivar Bountifulj ~ith ~ell-developed pri~ary lea~es~ The 29 pathogen ~as EE~i~he Doly~oni~ Tbe bean seedlings were spraysd Yith a 250-ppm solution of the test compou~d i~ an acetone~ater 31 ~i~tur~ containing a ~onio~ic emulsifier. ~he treated pla~ts ~ .
33~
were inoculated one day after spray application of the test 2 co~pound ~rith the p~thogen~ The plants ~ere then maintained in a 3 greenhouse at a 60-80~ r~l~ tive hu~idity and at a temperature of 4 68-70F~ ~hs rate of in~e~tion on the leaves ~as made after about 10 day~. The p6rcent disease control pro~ided by a give~
6 test compound ~as based on the disease reduction relative to 7 untreated check plants~ The compounds found to be effective at 8 the test concentrations and the results are tabulated in Table 9 III. The compounds found to be e~fective at the test concen- ~
10 trations and the results are tabulated in ~able II.
11 Exam~le 27 -- Fermentat~on Tect 12 An in-vitro test was carried out to determine the 13 influence of 3-(N-chloroacetyl-N-2,6-dimethvlphenylamin~)-gamma-14 butyrolactone ~Compou~d D-8) on yeas.ts responsible for the " ~ , 15 alcobolic fer-entation of grapes~ The test ~as condueted as ; 16 follo~s:
17 Erlenmeyer flasks ~S00 cc) vere ~filled with 200 cc~of 18 gra~pe juice~ (density 1O07 ~cc) extracted from bunc:hes of :: :
19 ~ ~ad~le ~ Anaevia~ grapest :The test compound was added to the grape juice and the extent of fermentation determined by 21 measuring the cuMulative loss of ~eight due to carbon dioxide 2~ escape. For comparison, the test ~as conducted with a~ untreated 23 chec~ a~d a commercial fungicide~ The concentration of test 24 compound and the results for the first 8 days of ~erme~tation ar~
2S tabulated iD Table rI.
33~
TABLE Vl: - :
F~Ementation Test 3 Cumulative loss of weight (in grams) 4 Product Conc. __ ___ __due_to_02_eSca~e_af_~r~
_add~d_ _~Pm_ l_d~y 2_days 3_days 4_days 7_daYs 8_d~s 6Comp. ~-8 1 0~9 5O010.5 11.3 14.2 14.5 7 2 0.8 5.210.4 11.1 13,4 13.7 8 4 1,0 5.210.~ 11.1 13.1 13.3 9 B loO 5~411~0 11~8 14~5 15~2 10Commercial 1 0.4 0.52.8 3.6 8.~ 10.1 llFungicide 2 0.~ 0.41.3 1.8 4.7 5.6 12 4 0.4 0.40~7 0.8 2.1 3~1 -13 8 0.3 0.40.7 0.7 1.2 1.5 14 None - 0.9 5.411.1 11~6 14.2 14~5 1S ~xa Ple_28__- Eradlcant Down~_Nmldew EQ~trol 16 3~ chloroacetyl N-2,6-dimethylphenylamino~-gamm~-17 butyrolactone (compound D-8) a~d s2Yeral com2ercial fun~icides 18 were tested for the eradicant control o~ do~ny mil~6s~ (PlasmoPaEa 19 riticola OD grape leaves. The commercial fungi~idss employ~d 2 0 w er e ~
2~ Captafol -- cis-N-(1rl,2,2-tetrachloroet~ylthio)-4- ..
22 cyclohexe~e :1,2-dicarbosimide 23 Pentinac`eta~e -- triphenyltin acetate ~4 Chl~othalonil -- 2,4,5,6-tetrachloroisophthalo~itrile 2~ Cupric sulfate :l :
26 Detached leav~s of Carignane and Er~peror grape pl~ nts 27 ~er~ us~d as hosts. The leaves were inoculated ~ith tha organism 28 and placed in an environment chamber and incubated at 18-22C and 29 at ~about 100% relative humidity for 1 to 3 days (1 to 2 days ~or 30 Emperor leaves, 3: days ~or Carigna~e ~eaves) . The leaYes ~ re 31 then sprayed ~ith a solution of the test compound in ac~tone.
32 ~he sprayed leaves were then maintained at 18-22C an~ at abDut 33 .. 100~ relative hum:idity. Eight to nine days after inoculation,
34 the amount of dis~ase control ~as determi~ed,, The percsnt
35 diseass control provided by a giverl test compound ~as based on
36 the percent disease r~3~uction relative to nontreated check
37 l~aves. The test composlnd, the grape leaf ~rari2ty, the time of :
~33~
1 treatment witb the test compound (days after in~culation) and the 2 results of ~D;S10 ~ppm of ~pplied spray f~r 50~ control) and 3 EDI9~O (ppm of applied spray for 90~ control) are tabul ted in 4 ~ab~a VII.
TABLE_YII
Eradican~ Grape~_Doyn~!_MlldeW_c_ntEl ~ Eadlcatlon ED~5~o~EDl9lo 8 _ EmDo}or_L_aves_ Cariqnane Leaves 9 Test ComPound , 1 dav 2 davs 3 da~s ~ _ _ _ _ Compound D-8 9~3~58 27~9920~7/t13 11 Captafol ~55/145 S4/168 20~/670 1~ Pentinacetate 47/171 8~f21~ 254~562 13 Chlorothalonil 128/293410~1000~ 313/992 14 Cupric sulfate* 118~289 204~445 380~610 ~Water used as solvsnt 16 ExamPle_29~ Eradlcant Downy_M ldew Eoatrol 17 A wettable po~der ~formulat,ion o~ 3-~N-chloroacetyl-N-18 2,6-dimat~ylphenyla~ino~-g~mma-butyrolactone _n attapulgite~clay :, 19 ~ras tested for the eradicant contr~l of grape dollrny milaew on grape-leaves. Three-month-old sin`gle-bud Caber~et Sauvignon 21 su~tings (cul~iv~tad in gr vel) contai~ing 6 to 10 leaves were 22 used as hosts. The unders1des o~ k~he leaYes ~ere sprayQd ~i~h a 23 sporangial suspension of Plasmo~ara vitlcola containing 510,000 24 conidia per ~illiliter of ~ater. ~he inoculated cuttin~s ~ere placed into a mistiny chamber~ An aqueous suspension containing 26 62.5 ppm of test compound was sprayed on the cuttings at a rate 27 of appr~ximat~ly 3.5 ml per 100 cm2 of leaves at four different 2a dates after the date of inDculation. ~en to 11 days after the 29 inoculation, the amount of disease control ~as determinPd. ~he perce~t disease control provided ~y the test compound ~as based 31 on the percent disease reduction relative to untreated ~heck 32 cutti~gs. The results are tabulated in Table YIII.
- 3~ -3~
TABLE YI EI
2 Eradica_t GraE~.e_Do~n~._Mild~Y Cntr 3 ïnterval between 4 inoculation and COTlC~, of fungicide treat- Fungicide % Leaf Sur- ~ Disaase 6 ment~ n_da!LsL-- ~ pmL__ f ace_Infected _ContEol_ 8 1 62.5 9.,51 97,6 9 2 0 14.3 ~-~
2 62.5 0.55 96.2 11 . 3 0 27.14 --12 3 61.5 4015 84.7 13 5 0 29,,a4 --14 5 62.5 2.5 91.6 EXam~le_30~___RealdUal_PreVe~tlVe~GEa~D_Wn~ M ldew_~ont_ol 16 . A ~ettable powder formulation oÇ 3- (N-chloroacetyl-N- ;
17 ~, 6-dimi3thylphenyla~in~J -gamma-butyrolactone in attapul~ite clay 18 ~as tested for residual preventive downy mildew control on grape 19 leaves~ Three-Dlonth-old single-b~d Cabernet Saurignon cuttings 20 (clllti~ated in gra~el), containing 5 to 8 leaves" s-er~ used as 2'1 hosts. The cutti~ngs were sprayed with an aqu~us suspensidn 22 containlng 160 ppm of the test compound at a rate of ~approxi-23 mately 4 ml/100 cmZ of leaves. Th2 cuttl~gs were then placed in 24 a~humid chamber at 90 to g5b relative hu~idity. Three days af~er 2S fungicide treatment, the underslaes of the leaves ~ere s prayed 26 with a sporangial suspe~si3n of Plasm~ara viticol_. ~he 27 inoculat2d cuttings were put into a misting chamber~ Eight to 10 28 days after the inoculation, the amount of.disease control was 29 determinea. ~he pe~cent di~ease control pro-lided by th~ test 30 ~ompo~n~ ~as hased on the percent disease reduction rel ti~ tD
31 untreated check cuttingsO The resul*s are ta~ulated in Table IX.
.
-- 3'7 --. .
3~
1 TA~LE IX
2 R_sldual Preventive GraPe_D_uny ~ ew on~ro 3 - Interval between 4 inoculation and Cono. of fungicid~ tr~at- Pu~gi~ide ~ Leaf sur- % Diseas~
ent~lln_da~sL~ pml;_ fac9_I fected _CatEl_ 7 3 0 12.81 -~
8 3 160 0.03 99~8 9 ~ Example 31 -- Control of Foliar Down~_~_ldQw Infect~on~b~ Root_Abs E tion 11 A 50b wettable powder ~ormulation of 3-(N-chloroacetyl-12 N 2~6-dimethylphenylamino~-gam~a-butyrolactone in attapulgite 13 clay was tested for the control of foliar grape do~ny mildew 14 inection ~y root absorption. Three-month-old single-bud :
Cabernet Saurignon cuttings (culti~ated in gravel), containing 9 16 to 12 leaves, were usd as hosts. ~he roots of ths cuttings ~ere 17 dipped for 6 hours in an aqueous sus'pension co~taining 50 ppm of , 18 the test compound. The cuttings ~era then repla~ted in gravel 19 and put into a misting chamber~ ~t four differant times after root treatment, the leaf unaersides were sprayed with a 21 sporangial suspensio~ of Plasmo~ra viticola. The inoculated 22 cuttings ~ere placed i~tolthe misting chamber to stimulate 23 disease de~elopment. Ten to 12.days after inoculatio~, the 24 amount of disease co~trol was determi~ed~ ~he percent dis~ase 25 control provided by the test compound ~as base~ o~ the percent 26 dis~ase reduotion rela~i~e to untrea~6d chec~ cuttings. The 27 results are tabulated l~ T3ble X.
.... .
~33~
1 treatment witb the test compound (days after in~culation) and the 2 results of ~D;S10 ~ppm of ~pplied spray f~r 50~ control) and 3 EDI9~O (ppm of applied spray for 90~ control) are tabul ted in 4 ~ab~a VII.
TABLE_YII
Eradican~ Grape~_Doyn~!_MlldeW_c_ntEl ~ Eadlcatlon ED~5~o~EDl9lo 8 _ EmDo}or_L_aves_ Cariqnane Leaves 9 Test ComPound , 1 dav 2 davs 3 da~s ~ _ _ _ _ Compound D-8 9~3~58 27~9920~7/t13 11 Captafol ~55/145 S4/168 20~/670 1~ Pentinacetate 47/171 8~f21~ 254~562 13 Chlorothalonil 128/293410~1000~ 313/992 14 Cupric sulfate* 118~289 204~445 380~610 ~Water used as solvsnt 16 ExamPle_29~ Eradlcant Downy_M ldew Eoatrol 17 A wettable po~der ~formulat,ion o~ 3-~N-chloroacetyl-N-18 2,6-dimat~ylphenyla~ino~-g~mma-butyrolactone _n attapulgite~clay :, 19 ~ras tested for the eradicant contr~l of grape dollrny milaew on grape-leaves. Three-month-old sin`gle-bud Caber~et Sauvignon 21 su~tings (cul~iv~tad in gr vel) contai~ing 6 to 10 leaves were 22 used as hosts. The unders1des o~ k~he leaYes ~ere sprayQd ~i~h a 23 sporangial suspension of Plasmo~ara vitlcola containing 510,000 24 conidia per ~illiliter of ~ater. ~he inoculated cuttin~s ~ere placed into a mistiny chamber~ An aqueous suspension containing 26 62.5 ppm of test compound was sprayed on the cuttings at a rate 27 of appr~ximat~ly 3.5 ml per 100 cm2 of leaves at four different 2a dates after the date of inDculation. ~en to 11 days after the 29 inoculation, the amount of disease control ~as determinPd. ~he perce~t disease control provided ~y the test compound ~as based 31 on the percent disease reduction relative to untreated ~heck 32 cutti~gs. The results are tabulated in Table YIII.
- 3~ -3~
TABLE YI EI
2 Eradica_t GraE~.e_Do~n~._Mild~Y Cntr 3 ïnterval between 4 inoculation and COTlC~, of fungicide treat- Fungicide % Leaf Sur- ~ Disaase 6 ment~ n_da!LsL-- ~ pmL__ f ace_Infected _ContEol_ 8 1 62.5 9.,51 97,6 9 2 0 14.3 ~-~
2 62.5 0.55 96.2 11 . 3 0 27.14 --12 3 61.5 4015 84.7 13 5 0 29,,a4 --14 5 62.5 2.5 91.6 EXam~le_30~___RealdUal_PreVe~tlVe~GEa~D_Wn~ M ldew_~ont_ol 16 . A ~ettable powder formulation oÇ 3- (N-chloroacetyl-N- ;
17 ~, 6-dimi3thylphenyla~in~J -gamma-butyrolactone in attapul~ite clay 18 ~as tested for residual preventive downy mildew control on grape 19 leaves~ Three-Dlonth-old single-b~d Cabernet Saurignon cuttings 20 (clllti~ated in gra~el), containing 5 to 8 leaves" s-er~ used as 2'1 hosts. The cutti~ngs were sprayed with an aqu~us suspensidn 22 containlng 160 ppm of the test compound at a rate of ~approxi-23 mately 4 ml/100 cmZ of leaves. Th2 cuttl~gs were then placed in 24 a~humid chamber at 90 to g5b relative hu~idity. Three days af~er 2S fungicide treatment, the underslaes of the leaves ~ere s prayed 26 with a sporangial suspe~si3n of Plasm~ara viticol_. ~he 27 inoculat2d cuttings were put into a misting chamber~ Eight to 10 28 days after the inoculation, the amount of.disease control was 29 determinea. ~he pe~cent di~ease control pro-lided by th~ test 30 ~ompo~n~ ~as hased on the percent disease reduction rel ti~ tD
31 untreated check cuttingsO The resul*s are ta~ulated in Table IX.
.
-- 3'7 --. .
3~
1 TA~LE IX
2 R_sldual Preventive GraPe_D_uny ~ ew on~ro 3 - Interval between 4 inoculation and Cono. of fungicid~ tr~at- Pu~gi~ide ~ Leaf sur- % Diseas~
ent~lln_da~sL~ pml;_ fac9_I fected _CatEl_ 7 3 0 12.81 -~
8 3 160 0.03 99~8 9 ~ Example 31 -- Control of Foliar Down~_~_ldQw Infect~on~b~ Root_Abs E tion 11 A 50b wettable powder ~ormulation of 3-(N-chloroacetyl-12 N 2~6-dimethylphenylamino~-gam~a-butyrolactone in attapulgite 13 clay was tested for the control of foliar grape do~ny mildew 14 inection ~y root absorption. Three-month-old single-bud :
Cabernet Saurignon cuttings (culti~ated in gravel), containing 9 16 to 12 leaves, were usd as hosts. ~he roots of ths cuttings ~ere 17 dipped for 6 hours in an aqueous sus'pension co~taining 50 ppm of , 18 the test compound. The cuttings ~era then repla~ted in gravel 19 and put into a misting chamber~ ~t four differant times after root treatment, the leaf unaersides were sprayed with a 21 sporangial suspensio~ of Plasmo~ra viticola. The inoculated 22 cuttings ~ere placed i~tolthe misting chamber to stimulate 23 disease de~elopment. Ten to 12.days after inoculatio~, the 24 amount of disease co~trol was determi~ed~ ~he percent dis~ase 25 control provided by the test compound ~as base~ o~ the percent 26 dis~ase reduotion rela~i~e to untrea~6d chec~ cuttings. The 27 results are tabulated l~ T3ble X.
.... .
- 38 -TA BLE_X
2 Controa of GraPe Downy Mllde~ - bx Root AbsoE~tioa 3 Interval be~e~n 4 root ~roatment Con_. of and inoculation Fungicide ~ Leaf sur- % Dise~se 6 ~ lln_d_YsL ___ ~PPmL-- fac~o InecteL _CoatEol_ 7 1 0 10.92 --8 ~ 50 -6.26 33.5 11 9 0 lO.ll --: 12 9 ` 160 0.19 99 ` 13 16 0 39.35 --14 16 160 2Z.43 43 Exampl__32~ Co_trQl_of kottuce DownY ~lld~w 16 A 50% we*table po~der formulation of 3 (N-chloroaGetyl-, . 17 N-Z~6-dimethylphenylamino)-gamma-~utyrolactone i~ attapulgite :~ 18 clay was ~osted ~or the control of the lettuce downy mi}de~
1g organism, Br~mia:1actyca_ Lettuce see~s ~c~1ltivar Mar*yj ~were planted in plastic ' ~ . .
21 flats filled ~ith a miYtUre of 2/3 ~ompost and 1~3 sandy soil 22 The flats ~ere left i21 a greenhouse ( 17-24C~ . Si~ da~ys after 23 planting, the~lettuce seedlin~gs (cotyledon stage) ~er~ spra7ed 24 ~with an aqu~eous suspension of the~ test compound at various test 25 c~Deentrations ~(ODe flat~ per concentration level). One day after 26 fungicide application, the saedlings were sprayed ~ith a 27 sporangial suspe~sion containing 140,000 conidia of the org~nism 28 per millilitqr ~at~r. The seedlings were placed in a humid 29 chamber (12-14C, 12 hours ~sr day of artifical light). 2ight day~ after ino~ulation, the amount of disease ~ontrol ~as deter-31 mined by counting the ~umber of sur~iving seedlings per flat.
32 ~he resuLts for tho test compound, two co~ercial standards and 33 two u~treated checks are tabulated in Table XI.
- 3~ -., ~3~
1T~BLE_XI
2L~ttucQ_Do~ny_Mild~w Control 3Total No.
4 Rat~s Se~dlings ~ DQad . S T_FUngicldQ~ ~ active,l!hlper_flat Seedllnas CntE
- 6 Test Compound 25 689 SD 9 75~ a ;: 7 Te~t Co~pound 50 780 1.1 90.6 8 ~est Co~pound 100 780 2.3 95.5 9 Captafol 160 614 3.6 85,2 Baneb* 160 4~2 14.5 40.6 11Untr~ated u~co~-12taminated chec~ - 363 1.9 -- :
: 13Untreatsd contami~ .
14 nated ch~ck - 427 24.4 -- ;
~- 15 *Manganous ethyle~e bisdithiocarbamate :~ 16 Example 33 -- Prevsntive and Curati~e Coatro}__f_Ca,bbaqe_D_w ~ Ml_d_~
~8 A 50~ ~ettable powder formulation of 3~(N-chloroa_etyl-19 N-2~6-dimethylphQnylamlno~-gamma-butyrolactone i~ attapulgite clay ~as tested for the control of t'he cabbage downy milde~
21 organism, Perogospora ~ sitica ssp. brassiGLe.
22 PreYent}ve_Control ;23 ~ Cabbage seeds (culti-ar: ~ilan hatif d'Auhervilliers) 24 t~ere planted i:n pla~s~ lC flats co~taining a soil mi~t~re of 3 25 phrts ~co~post and 1 part sand~. ~he seeded flats wsre maintai~ed 26 i~ a high-humidity greenhouse er~ironment. Seven days after 27 planting~ 3 flats of ~abbage seedlings s~ere sprayed until runoff ~8 with an aqueous suspension of the test compouna at vari~us 29 coDc~entrations. ~o days fter f~ungicide applicatLon, the flats 30 of cabbage seedlings ::were prayed~rith an a~ue~us suspensio~ of 31 the conidia (about 300,000 per ml) of the or~arlism. Eleven days 32 after inoculatio~, amount of disase control ~as determiIleâ ~y 33 counti~ the number of disaased s~edlings a~c the l-leaf stage `
34 coYered 7rith~ a ~hi e mycelium. The results for flats treated 35 ~ith the test compound, a commerc:ial sta~dard and check fla~s are 36 tabulated in TabIe ~II.
_ .
3~
.
1 cu~at iv e cont ro 1 2 Cabbage seeds (cultivar Milan hatif a'Aubervilliers) 3 Y~re plantad in plastic flats containing a soil mixture of 3 4 parts compost and 1 par~ sand,. The seeded flats were maintained in a high-humidity enYiron~ent. Nine days a~ter plan~ing, 3 6 flats of cabbage seedlings were sprayed with an aqueous suspen-7 sion of the conidia (about 300~000 per ml) of the organism. Four 8 days after i~oc~lation, the flats were sprayed u~til runoff with 9 an a~ue~us suspension of the test compou~d at various . .
concQntrations. Seven days after funglcide application, th~
11 amount ~f disease control ~as determined by counting the number 1~ of diseased seedlings at the 1-leaf stage co~ered with white 13 myceliu~. The results for the flats treated with the tsst 14 compoundO a commercial standard and ~check flats are tabulated in Table XII.
16 ~ TABL~ XII
17 ~ Control of_Cabba~e_DovnY_glldew 18 ~ _ ~ Pre~entive___________ 19 . Rates Total ~ : la.i. No. of % Dis~ased 21, _ __ Punqi~id~ hl Seedll 9~ s_edliaqS_ control*
22 Compound D-8 80 231 1.5 98.5 23 Compound D-8 40 138 2.2 9~.7 24 Compound D-8 ~0 171 1.8 98.2 Cap~a~ol 160 1~1S9. 6 38. 9 26 None~inoculated - 17597~6 27 Non~:fnot irloculated~ - 177 1. 7 28 _~ Curative~
29 Rates Total ~0 a. io No. of % Diseased 31 ~ __ Fun~lclde~hl_ Seedli~s Seedlinqs~ Contr_l*
32 Compound ~-8 80 ~55 0.6 99.4 33 Compound D~8 40 203 1.0 99.0 34 Compouna D-8 20 165 1.8 98~2 Captafol 160 148 65.5 32.9 ~6 Non~inoculated 37 No~e~not inoculated 38 *Disease reduction relative to ch~ck flat which was not
2 Controa of GraPe Downy Mllde~ - bx Root AbsoE~tioa 3 Interval be~e~n 4 root ~roatment Con_. of and inoculation Fungicide ~ Leaf sur- % Dise~se 6 ~ lln_d_YsL ___ ~PPmL-- fac~o InecteL _CoatEol_ 7 1 0 10.92 --8 ~ 50 -6.26 33.5 11 9 0 lO.ll --: 12 9 ` 160 0.19 99 ` 13 16 0 39.35 --14 16 160 2Z.43 43 Exampl__32~ Co_trQl_of kottuce DownY ~lld~w 16 A 50% we*table po~der formulation of 3 (N-chloroaGetyl-, . 17 N-Z~6-dimethylphenylamino)-gamma-~utyrolactone i~ attapulgite :~ 18 clay was ~osted ~or the control of the lettuce downy mi}de~
1g organism, Br~mia:1actyca_ Lettuce see~s ~c~1ltivar Mar*yj ~were planted in plastic ' ~ . .
21 flats filled ~ith a miYtUre of 2/3 ~ompost and 1~3 sandy soil 22 The flats ~ere left i21 a greenhouse ( 17-24C~ . Si~ da~ys after 23 planting, the~lettuce seedlin~gs (cotyledon stage) ~er~ spra7ed 24 ~with an aqu~eous suspension of the~ test compound at various test 25 c~Deentrations ~(ODe flat~ per concentration level). One day after 26 fungicide application, the saedlings were sprayed ~ith a 27 sporangial suspe~sion containing 140,000 conidia of the org~nism 28 per millilitqr ~at~r. The seedlings were placed in a humid 29 chamber (12-14C, 12 hours ~sr day of artifical light). 2ight day~ after ino~ulation, the amount of disease ~ontrol ~as deter-31 mined by counting the ~umber of sur~iving seedlings per flat.
32 ~he resuLts for tho test compound, two co~ercial standards and 33 two u~treated checks are tabulated in Table XI.
- 3~ -., ~3~
1T~BLE_XI
2L~ttucQ_Do~ny_Mild~w Control 3Total No.
4 Rat~s Se~dlings ~ DQad . S T_FUngicldQ~ ~ active,l!hlper_flat Seedllnas CntE
- 6 Test Compound 25 689 SD 9 75~ a ;: 7 Te~t Co~pound 50 780 1.1 90.6 8 ~est Co~pound 100 780 2.3 95.5 9 Captafol 160 614 3.6 85,2 Baneb* 160 4~2 14.5 40.6 11Untr~ated u~co~-12taminated chec~ - 363 1.9 -- :
: 13Untreatsd contami~ .
14 nated ch~ck - 427 24.4 -- ;
~- 15 *Manganous ethyle~e bisdithiocarbamate :~ 16 Example 33 -- Prevsntive and Curati~e Coatro}__f_Ca,bbaqe_D_w ~ Ml_d_~
~8 A 50~ ~ettable powder formulation of 3~(N-chloroa_etyl-19 N-2~6-dimethylphQnylamlno~-gamma-butyrolactone i~ attapulgite clay ~as tested for the control of t'he cabbage downy milde~
21 organism, Perogospora ~ sitica ssp. brassiGLe.
22 PreYent}ve_Control ;23 ~ Cabbage seeds (culti-ar: ~ilan hatif d'Auhervilliers) 24 t~ere planted i:n pla~s~ lC flats co~taining a soil mi~t~re of 3 25 phrts ~co~post and 1 part sand~. ~he seeded flats wsre maintai~ed 26 i~ a high-humidity greenhouse er~ironment. Seven days after 27 planting~ 3 flats of ~abbage seedlings s~ere sprayed until runoff ~8 with an aqueous suspension of the test compouna at vari~us 29 coDc~entrations. ~o days fter f~ungicide applicatLon, the flats 30 of cabbage seedlings ::were prayed~rith an a~ue~us suspensio~ of 31 the conidia (about 300,000 per ml) of the or~arlism. Eleven days 32 after inoculatio~, amount of disase control ~as determiIleâ ~y 33 counti~ the number of disaased s~edlings a~c the l-leaf stage `
34 coYered 7rith~ a ~hi e mycelium. The results for flats treated 35 ~ith the test compound, a commerc:ial sta~dard and check fla~s are 36 tabulated in TabIe ~II.
_ .
3~
.
1 cu~at iv e cont ro 1 2 Cabbage seeds (cultivar Milan hatif a'Aubervilliers) 3 Y~re plantad in plastic flats containing a soil mixture of 3 4 parts compost and 1 par~ sand,. The seeded flats were maintained in a high-humidity enYiron~ent. Nine days a~ter plan~ing, 3 6 flats of cabbage seedlings were sprayed with an aqueous suspen-7 sion of the conidia (about 300~000 per ml) of the organism. Four 8 days after i~oc~lation, the flats were sprayed u~til runoff with 9 an a~ue~us suspension of the test compou~d at various . .
concQntrations. Seven days after funglcide application, th~
11 amount ~f disease control ~as determined by counting the number 1~ of diseased seedlings at the 1-leaf stage co~ered with white 13 myceliu~. The results for the flats treated with the tsst 14 compoundO a commercial standard and ~check flats are tabulated in Table XII.
16 ~ TABL~ XII
17 ~ Control of_Cabba~e_DovnY_glldew 18 ~ _ ~ Pre~entive___________ 19 . Rates Total ~ : la.i. No. of % Dis~ased 21, _ __ Punqi~id~ hl Seedll 9~ s_edliaqS_ control*
22 Compound D-8 80 231 1.5 98.5 23 Compound D-8 40 138 2.2 9~.7 24 Compound D-8 ~0 171 1.8 98.2 Cap~a~ol 160 1~1S9. 6 38. 9 26 None~inoculated - 17597~6 27 Non~:fnot irloculated~ - 177 1. 7 28 _~ Curative~
29 Rates Total ~0 a. io No. of % Diseased 31 ~ __ Fun~lclde~hl_ Seedli~s Seedlinqs~ Contr_l*
32 Compound ~-8 80 ~55 0.6 99.4 33 Compound D~8 40 203 1.0 99.0 34 Compouna D-8 20 165 1.8 98~2 Captafol 160 148 65.5 32.9 ~6 Non~inoculated 37 No~e~not inoculated 38 *Disease reduction relative to ch~ck flat which was not
39 treated ~ith fungicide.
-- 4~ --3~
1Exam~le-3~ Foliar-Treatmeat-of-cucum~er-Do~ny M~l_e~
2Compound D-8 w s tested by a foliar spray application 3 for the control of the cucumber downy milaew otga~ism Pseudo-4 ~eEonospora cukensls.
5a 3-week old cucumber plant (cultivar Nark~teer) was 6 sprayed ~ith a solution of the test compound i~ a 1% acetone/99%
7 ~ater suspension containin~ 40 ppm of a no~ionic sur~actant~
8 Four l~a~es ~ere dstachsd from the plant, dried and i~oculated by 9 spraylng with a spore SU5p' nsion of the organismO After inoculation, the leaYes uere kept at 20-~5C in a high-humidity 11 chamber~ ~fter 6 dayst th~ amount o disease-infection ~as 12 aetermined. Ths percent disease control provided by the test 13 compound vas based on the percent disease r~duction relative to 14 untreated check le~es. The test co,mpound, the test concen-tration and the percent co~trol are tabulated i~ Tahle XIII.
17Fo-mar S~EaY_Cntr Lof_Cucumber Do~nv_Milde~
18 Test:Com QundCo c. ~Pml ~ Coat_ol 19 Comp~ound D-8 100 100 ~0 Compound D-8 j :40 88 21 Compound D-8 16 63 22 Maneb 100 98.3 23 ~aneb 40 90 24 Maneb 16 80 25~XamPle-35~ 5ontr-~ of_Sna~dra~on CE~wn and RoQt R_t 26C`ompound D-8 ~.fas tested to determine its activity 27 ayainst t~e ~oro~rn and ~root ro* organism Phyto~hthora cr Pt-~ea on 28 snapdragon pla~.ts (cultivar Antirrhinum) . For comparison, 29 Captafol and ~ancozeb were i~cluded in the test.
30 . Soil_Drench 31Four pots filled with young plants wer~ transplated 32 into 13-c~ soil infected ~th the Drganism. ~orty ml o~ a ~00-33 ppm aqueo~s solutio~ o~ ths test compo~nd was pvured in the pots.
34 The plants were the~ maint~ined in a green~ouse for disease 3~
1 dev~lopment. Fi~e days after treatment, ~be plants war~ ra~ed 2 for leaf necrosis and wilt, and crown rotl The percen~ disease 3 control provided by ~he test compound was based on dise~se 4 reducti~n re1ated to non-treated check plants~ The results are tabulated in Table XIV.
6 Foliar S~ray 7 Young plants werQ transplated into l~-cm pots (4 8 filled ~ith soil in~ec~ed with the organism. The soil ~as 9 covered with a plastic covering and the plant oliage w s sprayed-to runoff wlth 100 ppm aqueous suspensio~ of the test compound.
11 ~he plants were thon placed in a greenhouse for disease 12 develop~ent. Five days a~ter treatment, the plants wer~ rated 13 for leaf necrosis and wilt, and cro~n~rot. The percent disease 14 control ~ro~ided by the te t compound was based on disease reducti~n related to non-treated check plants. The res~lts are 16 tabulated in Table XIV.
17 ~ TABLE X~V
18 ~ ~ Sna~gra~n Crovn and Roo~ ~ot Contro 19 ~ ~ %_Control___________ ~ Cog ound SQll_Drench ~oliar_s~E~Y
21 A ~ 100 97 22 Captafol 0 0 23 aancozeb* 0 0 24 *t~1,2-ethanediyl~is(carbamodithioato)~(2-)} manganese mi~
ture Yith ~ 1, 2-6thanediylbis~carbamodithioato)~(2-)} zinc 26 Example 37 -- 5ystemic Soil Drench Treatme~t 27 fQr Sa~flower crown and ~oot_Rot Control 28 Compound D-8 was tested to datermine its systemic 29 ~ctivity in soil-drench applications against the safflo~er crown 3D and root rot organismsO Phyto~hthoEa cr~o~e_ and P. ~aEasitica~
.
3? Two-~eek-41d safflo~er seed}ings ver6 used as hosts.
32 Pots con~ai~ing the seedli~gs were drench~d ~ a~ aqueous 33 suspe~sion o the test compound at YariOUs test conce~trations 34 5four pots per concentration level~. one day after tre.~me~t a spa~ of the organism was poured on ~he soil sur~ace i~ the pots.
33~
The spaw~ uas prepared by cultiva~ing the organism in a mixture 2 of oat flakes, p~tato dextrose and soil. ~he inoculatea 3 seedlings were thsn maintained in a greenhouse at 20-25C day and 4 15-20C night temp~ra~ure. Three to four ~eeks after inoculation, the plant roots and crown were rated for disease.
6 The percent diseas~ control provided by t~e tsst co~pound ~3 5 7 based on percent disease reduction relative to ~o~l-treated check 8 pla~ts. ~he test concentrations and the percent disease c~ntrol 9 are tabulatea in ~able XVI.
10 ~ABLE_XVL
11S a f ~lo ~e r Cr_w n and_R o o~_ kot C ontrol_by_S o~l_Drench 12Conc. _~ C,QntrO~
13 _ _ ~__C_m ound~ m P- CrXPtqea P _PLEasltlca 14 Co~pound D-B 100* 1~0 100 17 Standard*~ ~-ethoxy-3- 100 78 80 - 18 trichloromsthyl 1,294~-40 12 21 19 thiadiazole~ 16 0 0 *100 ppm = 50 micrograms/cmZ =4. 46 lbs/acre 21 ~*~.s. Patents 3~260,588 and 3,260,,725 22 E~ample 38 -- Systemic Soil Drench Treatm~n~
23 for Tobacco crown and Root ~ot Control 24 Compound ~-8 was tes~d to datermine i'æ sys~emic activity in soil~drench applications against the cro~n and root 26 rot organisms PhytoPhth_ra ~aE~sit ca and P. _rv~o~a.
27 Ten-~eek-old tobacco seed}ings ~cultivar Glurk) vere 28 usad as hosts. Pots containi~g the seedlings were dren~hed with 29 an aqueous solution o~ the test compound at various t~s~
30 concen~ra~ions ~4 pots per concentration level) . One d~ y after 31 treatme~t a spa~n of the o~ ganism ~as poured on the soil surface 32 in the pots. The spawn ~as prepared by cultivating the organism 33 in a mi~ture of oat. f lakes, potato dextrose and soil. The 34 inoculated seedlings were then maintained in a greenhouse t 20 :
~3 ~L33~
25C day ana 15-20C night temperatureO Three to four weeks 2 after inoculation, the plant roots and ~:rown were rated for 3 disease. ~he percent disease con*rol provided by tha test 4 compouI~d was based on percent disease reduction relative to non-5 tre~ted check pla~ts. ~he test concentra~ion aad the percent 6 disease control ar~ tabulated in Table XVII.
7TAB~E_XVII
8T_b3cco_Cro~n and Root Rot Control_b~_SQ~ reach 9Co~c. _ ______%_contr31~
tO __ ____Co-m~und~ m PO_CryPto~ea P _Par_sitlca 11 Compound D-8 100* lO0 lO0 12 Compound D-8 40 99.8 99~8 13 Compound D^8 1S 96 96 14 Standard** (5-ethoxy-3-100 80 52 trichloromethyl-1~2t4-40 48 30 16 - thiadiazolel 16 9 0 17 *100 ppm = 50 micrograms~cm2 - 4~46 lbs/acre 18 *~.,S. Pate~ts 3,260,,588 and 3~260"72~
19 ~ 39____Controa of_Phytophthora _ot_in Sueet Pe~eEs ~ ~0% wettable powder formulation of 3- ~U-c~loroacetyl-21 N-2~6-dimet~hy.~phenylami~)-gamma-butyrolactone in attapulgite 22 clay was tested for the control of Ph~toPhthora rot in sweet .
23 psppers caused by the soil~ habiting P~ytophthoE- ca~siçi 2 4 orga ~is~ ,.
Sweet pepper seealings Scultivar Doux de Valence) at 26 . the 4-leaf stage were pla:~ted in pots filled -ith a s'erili~ed 27 ~i~ed soil of 1~2 compost and 1~2 sandy soil. ~h~ pots ~ere then 28 inoculated ~ith the orga~ism by spreading a bed of oats grain 29 (contaminatsd with ~he PhYtoPhthora caPSiCi organis~) on the soil 30 surface and covering the bed ~ith a 1-cm depth of sterilized 31 soil. The sweet pepper seedlings were then sprayed to runoff 32 ~ith an aqusous suspension of the test compound at various test 33 conceD.trations (12 .pots per conc6n~ration lerel). The amou~t of 34 disease co~trol was determined by courltir.g the number of dead - 45 ~
3~
plants. The percent disease con~rol provided by the test 2 compoun~ was ~ased on the percent disease rPduction relative to 3 untr~ated check sesdlings. The results are tabulated ira Tabl~
4 XVIII.
Cntrl_f_P_P~er_PhXtE~hthr- R~
7 `Conc. of 8Fungicide ~ of Alive ~ Lsaf Surf ace g ~a S~eali~s ~_co~rol Dama~Qd _~
1:1 200 100 100 1~3 12 40Q ~00 1Q0 1.63 13 0 ;: 33.3 - 0 T~B~E ~ ~
.
"
~C_Rl Ar--N
\f H_f ~
O=C\ /CH 2 : ~ S
.. . . :
~ Elemental Ana ~ sis _ 16 ~ elting C1 S
17No ______Ar~ Rl : Poiat,__ Calc FouLd C31c Fognd 18 A~1 2,6-(C~)z~ClCH2 130-131 11~g 13.110.811.7 19 A-2 206-~CH~)z~ CH3C02CH2 124-125 -- -- 10.010.2 A-3 2-C}~6-CH3~ClCH2 13~137 22.3 23.610.011.0 21 A-4 2,6(CH3~CH30CHz 86-87 -- -- 10.911.2 22 A-S 2-Cl-6-CH3~CH3C02CH2 99-100 10.4 11.79.4 9.1 23 A-6 3,4-(Cl1z~ClCH2 oil 31.5 32.79.4 9.3 24 A-7 2~6-(CzHs) 2~ ClCH~108-114 10.912069.8 10~3 A-.8 2~6-(C2Hs)~ : CH~0C~274-82 -~ ~ ~~10.0 10~6 26 :A-9 2,3~(CH~)2~: ~lC~z 99-102 11~911.710.8 10.2 27~ A-10 2,3-(CH3)z~C}l30CH2 oil -~ ~~10.910.3 28 A-11 2-CH3-6-C2H5~ClC~z 110-120 57.8 57.815.85.82 29 A-12 2-CH3-6 C2Hs~CH30CH2 8a-go 62.4 62.516.B6~82 ~-13 2,3,6-tCH3)~CH30CHz 101-103 62.5 60~2~~.86.72 31 A 14 ~3~6-(CH3)3~ ClCH2104-107 57.856.5~5.8 5,82 32 . A-15 2,3,5,6-(CH~ClCH2 140-143 59.0 60.1l6.16.32 33 A-16 2,3,5,6-~C~3)~ CH30CH2122-12363.665.8~7~2 7.42 34 lCarbon 2~ydroge~ ~ = Phenyl , 33~
- 1 TABLE_B - Com~unds_of_the For~ula o ~ R l Ar~
I I
O~C\ ~C~ ,2 O
.
El~mental_Aaalysl s____ . ___ 3 m.p. 1~ C H ~1 X
4 No AE_ __~ Rl RZ ~C Ca1. Fd-_ Cal FQo Cal Fd Cal. ~d B-1 (13 ClCHz Cl 103-106 ~ - 22.421.0 6 ~-2 (1~ C~COzCH2 H 90-91 63.0 63.3 6.3 6.7 4.. 6 4.5 7 ~-~3 (1) HOCH2 ~ 173-174 63.9 63.2 6.5 6.6 5.3 4.4 8 9-4 (1) CH~OCH2 H 133-134 65.0 65.5 6.9 6.8 5.1 5.2 9 ~-5 ~ SCH2 H 84-86 ~ -- 8. 9 9O02 ~-6 (1~ CH~SCH2 H 77-78 ~ 10.99.12 11 B-7 (2) ClCH2 H oil ~ ~ 9.211.11 :
12 3~~ ~2) CH30CH2 H ~ oil 67.0 66.0 7.2 7.2 4.8 4.0 -- --13 B-9 ~ H3CH20CH2 H 73-75 66.0 66.0 7.3 7.24.8 5.0 14 B-10 (3) ClCH2 H 128-130 ~--, -~ ~~ ~~ ~~ ~- 11.513.2 . ~-11 (3)~ CH30CH~ H 1û4-105 66.9 67.5 7.5 7.5 4 6 4 5 --. --16 B-12 ~ C3H~oCHz H oil 66.9 66.9 7.6 7.54 6 4 1 - --17 B-13 (~) ClCH2 Br98-10.2 46~6 47r7 4~2 4~4 3~9 4~2 ~~- .~~
18 (1) ~2,6- (CH3) 2) P
1~ ~2) 2,396- (CH3) 3,~ :
~O t3) 2 ~ 3 ~ ~ ~ 5- (~ fi3 ) 4`J~
21 lChlc)rine ~Sul~ur .
__ ___C__ , C, mpouBds_o f_th e P orm u la O
,.
/C-R
Ar-N\
fH_f~l 2 O=C CH
O
... .. ~, 23 ___~_Elemental A alysis_ ~ _ 24 Melting C H 1~ X
No~ Ar Ri __ PQin ,C al. Fd- Cal Pd. Cal Fd. Cal. Fd.
26 C-1 (lj ClC~2121-122 ~ 11. 2 12. 5(Cl) 27 C-2 (11 CH30C~2 42 4669.0 72.,6 6.1 6.6 4.5 4.S
28 C-3 (1) ~rC~2116-118 -- ~ 22.1 21.5(~r~
29 C-4 (1) CH3SCHz 52-55 65.6: 62~,3 5.8 5~ 4 ~
C-5 (21 ClCE~2 . 110-113 63.3 63.3. 4.7 4.8 4.~ 4.5 31 C-6 (2) CH30CH2 109-111 6802 69.6 5.7 5O9 4.~ 5.3 -~
32 ~ (2-methylnaph'chyl) 33 ~ ~2) 1- (naphth~
~33~
u~ ~ ~ In ~ o ~ ~ ~ ~ ~ ~ ~D ~ O ~ ~ U~ ~ ~ a:~ co r~ ~1 In ~ ~
O ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ O ~i ~ r~i ~ ~ In ~ ~i o ~ ~ ~ I` o o I~aLr)ooLr)o~D~OOOOOO~ ~oo~DLn~
U q~
c~ ~r o ~ ~ u~ r ~ o r~ o ~ o ~r o er ~D ~ ~ ~ O U~ I O 1` 0 ~ 1` t' ~ ~ ~ U~ O ~ ~ U
~1 ~1 ~ L~ O L(l ~ 0 1~ N ,1 ~ ~ ~ O ~ ~J u~
p; I ~ ~ ' ' ~; ~ ~ ` : :
o u /~ /c~ ~ u u u u u u r~ - u o u u u ~ m u u ~ u~u u ` ~ ~ x 3~ x y ~ u a ~ ' v o, E S ~ ~ ~ S ~ S ~ s s 3s ~ s s s s s s s S E X E 4 ~ ~ s S s ~ E ~ E E
') N N N C~ ~ N 5'~ 1 N ~ N t~l N ~ N
O ~O .~ l ~ ~ Ul ~ 1'~ o ~ r u~
aa~aaaa~a I I I I I I I I I I I I I J l l Q Q a a a a a ~ a a a a a a a a ~ :
.... .. ~ - , .
~33~;~
2% Control 3Tomato La~e ~ ht____ ___GEa~e D~ nY Mll~e ____ 4No PEeventative Eradicatlve ~r~ventatlve ~Eadlcatlve (ppm) (pp~) (ppm) (ppm) A-1 ga 84~100~ 82(40) 5tlOO) 7 ~-2 t4 -- 54~100) 3~lOO) 8 A-3 100 42(100~ 84(16) 7(lOO) 9 A-4 96(40) 81(100) - 98(100) 10(100) A-5 29 ~ 0(10O) 11 A-6 23 -- -- 0~100) 12 A-7 98 54 93(16~ 80(16) 13 A-8 26~100~ 0(100 14 A-9 68~0~ -- 95(100) 12(100) A-10 B9(100) gS 95(100~ 80(100) 16 ~-11 80 -~ 78~100) --17 ~-12 89 ~
18 A-13 100 -- 89(40~ -19 A-14 100 -- 89(40) ~0 A-15 37 -~ 54(100~ --21 A-16 100 -- 87(100) --22 B-1 100 : 92~100~ 97~40~ 88(100) 23 B-2 B8 ~~ 95(100) 9(100) 24 B-3 92(100) 92(100~ 95(100) 0(100) B-4 a8~16~ 96(40) 100(40) 95(16) 26 9 ~ 84 58 __ 73(100) 27 ~-6 97 96 95(100) 54~lOO) 28 ~-7 77 - 45(100~ --29 B-8 100 93(100~ 97(10~
B-9 97 __ __ __ 31 B-10 37 -- ~~ ~~
32 B-11 10D -~
34 B~13: :84 C-1 ~100 . -55(100) 96(16) 84(16~
36 C-2 : 86(~6) ~ - 94(~00) 37 C-3 45 -- __ __ 38 C-~ 5~ -- -- --3~ C-5 ~5(100) -~
42Saffloyer~cEown and Boot~Rot Control_ ~_Soil_Drench 43 ~Co~c. ~ ontEol _____ __ 44 __ __ __Compound~m D. cryPto~ea P _Parasitica Compound B-4 100* 98 100 47 16 14 ~97 48 Sta~dard~* (5-ethoxy-3-100 78 98 49 trichlorom~thyl-1,2,4-~0 12 78 thiadiazole1 16 0 17 , 51 ~100 ppm = 50 micrograms/cmZ = 4.46 l~s/acre 52 ~*~.S~ Patents 3~260,588 an~ 3~260,725 ~ .
3~
3 .' , ' '~
~ .
V~
~ Q.) ~ : ' :
~rl ~1 ~
O ~ .' H O 1~
3 ~ s ~ ~ o.~
''-: :
~:
.~ . S
~~
~m I I ~cr I ou~ I I, ~ou.
td ~a O ~ ~ ~ ~ ~ ~ I` o~ ~ o ~ ~ ~ ~r In ~ I` ~ a~ o ~ ~ ~ ~ Ln " oQQaaaac~Q~IIIIIIIIII~IIII~ :
a c~ ~ ~ a ~ a a a a c~ a q a a q .
33~ .
TABLE IV ~ TABLE V
: `% Preventative ~ ~radicatisn of.
Compound ~owny Mildew Compound Downy Mildew _NQ. _ Control _ No. l day 2 days '!
D- 1 31 D_ 1 ~ 94 D- 2 6 D_ 2 82 --D- 3 15 j~- 3 45 1?- 5 91: D- 7 -- 78 : D- 6 93 D- 8 ---- 100 D~ 7 44 D- 9 --- 73 D-:8 : 85 D- 11 95 D- 9 93 D~ 91 D- 12 :47 D- 14 --- 93:
D- 13 :: 87 D- 15 92 ----D- 14 53 ~ 16 54 D- 15 : ~85 D--17 87 ----~:: : D-~ 16 9 4 ~ D- 18 89 ----17 ~ 13 :V 19 68 : ~D- ~1 9 ~ ~ ~31 :~: : D--20 ---- 29 : D - 2 0 ~ 9 8 D- 2 1 ---- 3 9 : 'D- 21 69 j D - 23 54 __ D-- 22 15 D-24 68 __ D- 23 44 D- 25 ~-- 29 : D- 24 92 :~ i':
, .
-,
-- 4~ --3~
1Exam~le-3~ Foliar-Treatmeat-of-cucum~er-Do~ny M~l_e~
2Compound D-8 w s tested by a foliar spray application 3 for the control of the cucumber downy milaew otga~ism Pseudo-4 ~eEonospora cukensls.
5a 3-week old cucumber plant (cultivar Nark~teer) was 6 sprayed ~ith a solution of the test compound i~ a 1% acetone/99%
7 ~ater suspension containin~ 40 ppm of a no~ionic sur~actant~
8 Four l~a~es ~ere dstachsd from the plant, dried and i~oculated by 9 spraylng with a spore SU5p' nsion of the organismO After inoculation, the leaYes uere kept at 20-~5C in a high-humidity 11 chamber~ ~fter 6 dayst th~ amount o disease-infection ~as 12 aetermined. Ths percent disease control provided by the test 13 compound vas based on the percent disease r~duction relative to 14 untreated check le~es. The test co,mpound, the test concen-tration and the percent co~trol are tabulated i~ Tahle XIII.
17Fo-mar S~EaY_Cntr Lof_Cucumber Do~nv_Milde~
18 Test:Com QundCo c. ~Pml ~ Coat_ol 19 Comp~ound D-8 100 100 ~0 Compound D-8 j :40 88 21 Compound D-8 16 63 22 Maneb 100 98.3 23 ~aneb 40 90 24 Maneb 16 80 25~XamPle-35~ 5ontr-~ of_Sna~dra~on CE~wn and RoQt R_t 26C`ompound D-8 ~.fas tested to determine its activity 27 ayainst t~e ~oro~rn and ~root ro* organism Phyto~hthora cr Pt-~ea on 28 snapdragon pla~.ts (cultivar Antirrhinum) . For comparison, 29 Captafol and ~ancozeb were i~cluded in the test.
30 . Soil_Drench 31Four pots filled with young plants wer~ transplated 32 into 13-c~ soil infected ~th the Drganism. ~orty ml o~ a ~00-33 ppm aqueo~s solutio~ o~ ths test compo~nd was pvured in the pots.
34 The plants were the~ maint~ined in a green~ouse for disease 3~
1 dev~lopment. Fi~e days after treatment, ~be plants war~ ra~ed 2 for leaf necrosis and wilt, and crown rotl The percen~ disease 3 control provided by ~he test compound was based on dise~se 4 reducti~n re1ated to non-treated check plants~ The results are tabulated in Table XIV.
6 Foliar S~ray 7 Young plants werQ transplated into l~-cm pots (4 8 filled ~ith soil in~ec~ed with the organism. The soil ~as 9 covered with a plastic covering and the plant oliage w s sprayed-to runoff wlth 100 ppm aqueous suspensio~ of the test compound.
11 ~he plants were thon placed in a greenhouse for disease 12 develop~ent. Five days a~ter treatment, the plants wer~ rated 13 for leaf necrosis and wilt, and cro~n~rot. The percent disease 14 control ~ro~ided by the te t compound was based on disease reducti~n related to non-treated check plants. The res~lts are 16 tabulated in Table XIV.
17 ~ TABLE X~V
18 ~ ~ Sna~gra~n Crovn and Roo~ ~ot Contro 19 ~ ~ %_Control___________ ~ Cog ound SQll_Drench ~oliar_s~E~Y
21 A ~ 100 97 22 Captafol 0 0 23 aancozeb* 0 0 24 *t~1,2-ethanediyl~is(carbamodithioato)~(2-)} manganese mi~
ture Yith ~ 1, 2-6thanediylbis~carbamodithioato)~(2-)} zinc 26 Example 37 -- 5ystemic Soil Drench Treatme~t 27 fQr Sa~flower crown and ~oot_Rot Control 28 Compound D-8 was tested to datermine its systemic 29 ~ctivity in soil-drench applications against the safflo~er crown 3D and root rot organismsO Phyto~hthoEa cr~o~e_ and P. ~aEasitica~
.
3? Two-~eek-41d safflo~er seed}ings ver6 used as hosts.
32 Pots con~ai~ing the seedli~gs were drench~d ~ a~ aqueous 33 suspe~sion o the test compound at YariOUs test conce~trations 34 5four pots per concentration level~. one day after tre.~me~t a spa~ of the organism was poured on ~he soil sur~ace i~ the pots.
33~
The spaw~ uas prepared by cultiva~ing the organism in a mixture 2 of oat flakes, p~tato dextrose and soil. ~he inoculatea 3 seedlings were thsn maintained in a greenhouse at 20-25C day and 4 15-20C night temp~ra~ure. Three to four ~eeks after inoculation, the plant roots and crown were rated for disease.
6 The percent diseas~ control provided by t~e tsst co~pound ~3 5 7 based on percent disease reduction relative to ~o~l-treated check 8 pla~ts. ~he test concentrations and the percent disease c~ntrol 9 are tabulatea in ~able XVI.
10 ~ABLE_XVL
11S a f ~lo ~e r Cr_w n and_R o o~_ kot C ontrol_by_S o~l_Drench 12Conc. _~ C,QntrO~
13 _ _ ~__C_m ound~ m P- CrXPtqea P _PLEasltlca 14 Co~pound D-B 100* 1~0 100 17 Standard*~ ~-ethoxy-3- 100 78 80 - 18 trichloromsthyl 1,294~-40 12 21 19 thiadiazole~ 16 0 0 *100 ppm = 50 micrograms/cmZ =4. 46 lbs/acre 21 ~*~.s. Patents 3~260,588 and 3,260,,725 22 E~ample 38 -- Systemic Soil Drench Treatm~n~
23 for Tobacco crown and Root ~ot Control 24 Compound ~-8 was tes~d to datermine i'æ sys~emic activity in soil~drench applications against the cro~n and root 26 rot organisms PhytoPhth_ra ~aE~sit ca and P. _rv~o~a.
27 Ten-~eek-old tobacco seed}ings ~cultivar Glurk) vere 28 usad as hosts. Pots containi~g the seedlings were dren~hed with 29 an aqueous solution o~ the test compound at various t~s~
30 concen~ra~ions ~4 pots per concentration level) . One d~ y after 31 treatme~t a spa~n of the o~ ganism ~as poured on the soil surface 32 in the pots. The spawn ~as prepared by cultivating the organism 33 in a mi~ture of oat. f lakes, potato dextrose and soil. The 34 inoculated seedlings were then maintained in a greenhouse t 20 :
~3 ~L33~
25C day ana 15-20C night temperatureO Three to four weeks 2 after inoculation, the plant roots and ~:rown were rated for 3 disease. ~he percent disease con*rol provided by tha test 4 compouI~d was based on percent disease reduction relative to non-5 tre~ted check pla~ts. ~he test concentra~ion aad the percent 6 disease control ar~ tabulated in Table XVII.
7TAB~E_XVII
8T_b3cco_Cro~n and Root Rot Control_b~_SQ~ reach 9Co~c. _ ______%_contr31~
tO __ ____Co-m~und~ m PO_CryPto~ea P _Par_sitlca 11 Compound D-8 100* lO0 lO0 12 Compound D-8 40 99.8 99~8 13 Compound D^8 1S 96 96 14 Standard** (5-ethoxy-3-100 80 52 trichloromethyl-1~2t4-40 48 30 16 - thiadiazolel 16 9 0 17 *100 ppm = 50 micrograms~cm2 - 4~46 lbs/acre 18 *~.,S. Pate~ts 3,260,,588 and 3~260"72~
19 ~ 39____Controa of_Phytophthora _ot_in Sueet Pe~eEs ~ ~0% wettable powder formulation of 3- ~U-c~loroacetyl-21 N-2~6-dimet~hy.~phenylami~)-gamma-butyrolactone in attapulgite 22 clay was tested for the control of Ph~toPhthora rot in sweet .
23 psppers caused by the soil~ habiting P~ytophthoE- ca~siçi 2 4 orga ~is~ ,.
Sweet pepper seealings Scultivar Doux de Valence) at 26 . the 4-leaf stage were pla:~ted in pots filled -ith a s'erili~ed 27 ~i~ed soil of 1~2 compost and 1~2 sandy soil. ~h~ pots ~ere then 28 inoculated ~ith the orga~ism by spreading a bed of oats grain 29 (contaminatsd with ~he PhYtoPhthora caPSiCi organis~) on the soil 30 surface and covering the bed ~ith a 1-cm depth of sterilized 31 soil. The sweet pepper seedlings were then sprayed to runoff 32 ~ith an aqusous suspension of the test compound at various test 33 conceD.trations (12 .pots per conc6n~ration lerel). The amou~t of 34 disease co~trol was determined by courltir.g the number of dead - 45 ~
3~
plants. The percent disease con~rol provided by the test 2 compoun~ was ~ased on the percent disease rPduction relative to 3 untr~ated check sesdlings. The results are tabulated ira Tabl~
4 XVIII.
Cntrl_f_P_P~er_PhXtE~hthr- R~
7 `Conc. of 8Fungicide ~ of Alive ~ Lsaf Surf ace g ~a S~eali~s ~_co~rol Dama~Qd _~
1:1 200 100 100 1~3 12 40Q ~00 1Q0 1.63 13 0 ;: 33.3 - 0 T~B~E ~ ~
.
"
~C_Rl Ar--N
\f H_f ~
O=C\ /CH 2 : ~ S
.. . . :
~ Elemental Ana ~ sis _ 16 ~ elting C1 S
17No ______Ar~ Rl : Poiat,__ Calc FouLd C31c Fognd 18 A~1 2,6-(C~)z~ClCH2 130-131 11~g 13.110.811.7 19 A-2 206-~CH~)z~ CH3C02CH2 124-125 -- -- 10.010.2 A-3 2-C}~6-CH3~ClCH2 13~137 22.3 23.610.011.0 21 A-4 2,6(CH3~CH30CHz 86-87 -- -- 10.911.2 22 A-S 2-Cl-6-CH3~CH3C02CH2 99-100 10.4 11.79.4 9.1 23 A-6 3,4-(Cl1z~ClCH2 oil 31.5 32.79.4 9.3 24 A-7 2~6-(CzHs) 2~ ClCH~108-114 10.912069.8 10~3 A-.8 2~6-(C2Hs)~ : CH~0C~274-82 -~ ~ ~~10.0 10~6 26 :A-9 2,3~(CH~)2~: ~lC~z 99-102 11~911.710.8 10.2 27~ A-10 2,3-(CH3)z~C}l30CH2 oil -~ ~~10.910.3 28 A-11 2-CH3-6-C2H5~ClC~z 110-120 57.8 57.815.85.82 29 A-12 2-CH3-6 C2Hs~CH30CH2 8a-go 62.4 62.516.B6~82 ~-13 2,3,6-tCH3)~CH30CHz 101-103 62.5 60~2~~.86.72 31 A 14 ~3~6-(CH3)3~ ClCH2104-107 57.856.5~5.8 5,82 32 . A-15 2,3,5,6-(CH~ClCH2 140-143 59.0 60.1l6.16.32 33 A-16 2,3,5,6-~C~3)~ CH30CH2122-12363.665.8~7~2 7.42 34 lCarbon 2~ydroge~ ~ = Phenyl , 33~
- 1 TABLE_B - Com~unds_of_the For~ula o ~ R l Ar~
I I
O~C\ ~C~ ,2 O
.
El~mental_Aaalysl s____ . ___ 3 m.p. 1~ C H ~1 X
4 No AE_ __~ Rl RZ ~C Ca1. Fd-_ Cal FQo Cal Fd Cal. ~d B-1 (13 ClCHz Cl 103-106 ~ - 22.421.0 6 ~-2 (1~ C~COzCH2 H 90-91 63.0 63.3 6.3 6.7 4.. 6 4.5 7 ~-~3 (1) HOCH2 ~ 173-174 63.9 63.2 6.5 6.6 5.3 4.4 8 9-4 (1) CH~OCH2 H 133-134 65.0 65.5 6.9 6.8 5.1 5.2 9 ~-5 ~ SCH2 H 84-86 ~ -- 8. 9 9O02 ~-6 (1~ CH~SCH2 H 77-78 ~ 10.99.12 11 B-7 (2) ClCH2 H oil ~ ~ 9.211.11 :
12 3~~ ~2) CH30CH2 H ~ oil 67.0 66.0 7.2 7.2 4.8 4.0 -- --13 B-9 ~ H3CH20CH2 H 73-75 66.0 66.0 7.3 7.24.8 5.0 14 B-10 (3) ClCH2 H 128-130 ~--, -~ ~~ ~~ ~~ ~- 11.513.2 . ~-11 (3)~ CH30CH~ H 1û4-105 66.9 67.5 7.5 7.5 4 6 4 5 --. --16 B-12 ~ C3H~oCHz H oil 66.9 66.9 7.6 7.54 6 4 1 - --17 B-13 (~) ClCH2 Br98-10.2 46~6 47r7 4~2 4~4 3~9 4~2 ~~- .~~
18 (1) ~2,6- (CH3) 2) P
1~ ~2) 2,396- (CH3) 3,~ :
~O t3) 2 ~ 3 ~ ~ ~ 5- (~ fi3 ) 4`J~
21 lChlc)rine ~Sul~ur .
__ ___C__ , C, mpouBds_o f_th e P orm u la O
,.
/C-R
Ar-N\
fH_f~l 2 O=C CH
O
... .. ~, 23 ___~_Elemental A alysis_ ~ _ 24 Melting C H 1~ X
No~ Ar Ri __ PQin ,C al. Fd- Cal Pd. Cal Fd. Cal. Fd.
26 C-1 (lj ClC~2121-122 ~ 11. 2 12. 5(Cl) 27 C-2 (11 CH30C~2 42 4669.0 72.,6 6.1 6.6 4.5 4.S
28 C-3 (1) ~rC~2116-118 -- ~ 22.1 21.5(~r~
29 C-4 (1) CH3SCHz 52-55 65.6: 62~,3 5.8 5~ 4 ~
C-5 (21 ClCE~2 . 110-113 63.3 63.3. 4.7 4.8 4.~ 4.5 31 C-6 (2) CH30CH2 109-111 6802 69.6 5.7 5O9 4.~ 5.3 -~
32 ~ (2-methylnaph'chyl) 33 ~ ~2) 1- (naphth~
~33~
u~ ~ ~ In ~ o ~ ~ ~ ~ ~ ~ ~D ~ O ~ ~ U~ ~ ~ a:~ co r~ ~1 In ~ ~
O ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ O ~i ~ r~i ~ ~ In ~ ~i o ~ ~ ~ I` o o I~aLr)ooLr)o~D~OOOOOO~ ~oo~DLn~
U q~
c~ ~r o ~ ~ u~ r ~ o r~ o ~ o ~r o er ~D ~ ~ ~ O U~ I O 1` 0 ~ 1` t' ~ ~ ~ U~ O ~ ~ U
~1 ~1 ~ L~ O L(l ~ 0 1~ N ,1 ~ ~ ~ O ~ ~J u~
p; I ~ ~ ' ' ~; ~ ~ ` : :
o u /~ /c~ ~ u u u u u u r~ - u o u u u ~ m u u ~ u~u u ` ~ ~ x 3~ x y ~ u a ~ ' v o, E S ~ ~ ~ S ~ S ~ s s 3s ~ s s s s s s s S E X E 4 ~ ~ s S s ~ E ~ E E
') N N N C~ ~ N 5'~ 1 N ~ N t~l N ~ N
O ~O .~ l ~ ~ Ul ~ 1'~ o ~ r u~
aa~aaaa~a I I I I I I I I I I I I I J l l Q Q a a a a a ~ a a a a a a a a ~ :
.... .. ~ - , .
~33~;~
2% Control 3Tomato La~e ~ ht____ ___GEa~e D~ nY Mll~e ____ 4No PEeventative Eradicatlve ~r~ventatlve ~Eadlcatlve (ppm) (pp~) (ppm) (ppm) A-1 ga 84~100~ 82(40) 5tlOO) 7 ~-2 t4 -- 54~100) 3~lOO) 8 A-3 100 42(100~ 84(16) 7(lOO) 9 A-4 96(40) 81(100) - 98(100) 10(100) A-5 29 ~ 0(10O) 11 A-6 23 -- -- 0~100) 12 A-7 98 54 93(16~ 80(16) 13 A-8 26~100~ 0(100 14 A-9 68~0~ -- 95(100) 12(100) A-10 B9(100) gS 95(100~ 80(100) 16 ~-11 80 -~ 78~100) --17 ~-12 89 ~
18 A-13 100 -- 89(40~ -19 A-14 100 -- 89(40) ~0 A-15 37 -~ 54(100~ --21 A-16 100 -- 87(100) --22 B-1 100 : 92~100~ 97~40~ 88(100) 23 B-2 B8 ~~ 95(100) 9(100) 24 B-3 92(100) 92(100~ 95(100) 0(100) B-4 a8~16~ 96(40) 100(40) 95(16) 26 9 ~ 84 58 __ 73(100) 27 ~-6 97 96 95(100) 54~lOO) 28 ~-7 77 - 45(100~ --29 B-8 100 93(100~ 97(10~
B-9 97 __ __ __ 31 B-10 37 -- ~~ ~~
32 B-11 10D -~
34 B~13: :84 C-1 ~100 . -55(100) 96(16) 84(16~
36 C-2 : 86(~6) ~ - 94(~00) 37 C-3 45 -- __ __ 38 C-~ 5~ -- -- --3~ C-5 ~5(100) -~
42Saffloyer~cEown and Boot~Rot Control_ ~_Soil_Drench 43 ~Co~c. ~ ontEol _____ __ 44 __ __ __Compound~m D. cryPto~ea P _Parasitica Compound B-4 100* 98 100 47 16 14 ~97 48 Sta~dard~* (5-ethoxy-3-100 78 98 49 trichlorom~thyl-1,2,4-~0 12 78 thiadiazole1 16 0 17 , 51 ~100 ppm = 50 micrograms/cmZ = 4.46 l~s/acre 52 ~*~.S~ Patents 3~260,588 an~ 3~260,725 ~ .
3~
3 .' , ' '~
~ .
V~
~ Q.) ~ : ' :
~rl ~1 ~
O ~ .' H O 1~
3 ~ s ~ ~ o.~
''-: :
~:
.~ . S
~~
~m I I ~cr I ou~ I I, ~ou.
td ~a O ~ ~ ~ ~ ~ ~ I` o~ ~ o ~ ~ ~ ~r In ~ I` ~ a~ o ~ ~ ~ ~ Ln " oQQaaaac~Q~IIIIIIIIII~IIII~ :
a c~ ~ ~ a ~ a a a a c~ a q a a q .
33~ .
TABLE IV ~ TABLE V
: `% Preventative ~ ~radicatisn of.
Compound ~owny Mildew Compound Downy Mildew _NQ. _ Control _ No. l day 2 days '!
D- 1 31 D_ 1 ~ 94 D- 2 6 D_ 2 82 --D- 3 15 j~- 3 45 1?- 5 91: D- 7 -- 78 : D- 6 93 D- 8 ---- 100 D~ 7 44 D- 9 --- 73 D-:8 : 85 D- 11 95 D- 9 93 D~ 91 D- 12 :47 D- 14 --- 93:
D- 13 :: 87 D- 15 92 ----D- 14 53 ~ 16 54 D- 15 : ~85 D--17 87 ----~:: : D-~ 16 9 4 ~ D- 18 89 ----17 ~ 13 :V 19 68 : ~D- ~1 9 ~ ~ ~31 :~: : D--20 ---- 29 : D - 2 0 ~ 9 8 D- 2 1 ---- 3 9 : 'D- 21 69 j D - 23 54 __ D-- 22 15 D-24 68 __ D- 23 44 D- 25 ~-- 29 : D- 24 92 :~ i':
, .
-,
Claims (6)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A method for the control of fungi which comprises con-tacting said fungi or their habitats with a fungicidally effective amount of a compound of the formula (IV) wherein Ar is phenyl, naphthyl, or phenyl or naphthyl sub-stituted with 1 to 4 of the same or different substituents selected from fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms; R1 is alkyl of 1 to 6 carbon atoms, alkanoyloxymethyl of 1 to 6 carbon atoms, phenyl, phenyl substituted with 1 to 4 of the same or different substituents selected from fluoro, chloro, bromo, alkyl of 1 to 4 carbon atoms or alkoxy of 1 to 4 carbon atoms, halovinyl of 1 to 3 of the same or different halogens selected from fluoro, chloro or bromo; and R2 is hydrogen, chloro, bromo, alkyl of 1 to 6 carbon atoms, phenyl or phenyl substituted with 1 to 2 of the same or different substituents selected from fluoro, chloro, bromo and alkyl of 1 to 6 carbon atoms.
2. A method according to claim 1 wherein said compound represented by the formula (IV) wherein Ar is phenyl or substituted phenyl as defined in claim 1, R1 and R2 have the same significance as defined in claim 1.
3. A method according to claim 1 wherein said compound is represented by the formula (IV) wherein Ar is naphthyl or substituted naphthyl as defined in claim 1 and R1 and R2 have the same significance as defined in claim 1.
4. A method according to claim 3 wherein, in said compound R1 is chloromethyl or alkoxymethyl and R2 is methyl.
5. A method for controlling the growth of Phytophthora infestans fungi which comprises applying to said fungi or their habitats a fungicidally effective amount of a compound of the formula (IV) wherein Ar, R1 and R2 are as defined in claim 1.
6. A method for controll.ing the growth of Plasmopara viticola fungi which comprises applying to said fungi or their habitats a fungicidally effective amount of a aompound of the formula (IV) wherein Ar, R1 and R2 are as defined in claim 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA295,281A CA1113385A (en) | 1978-01-19 | 1978-01-19 | Fungicidal 3-(n-acyl-n-arylamino)-gamma- butyrolactones, gamma-butyrothiolactones and gamma- butyrolactams |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA295,281A CA1113385A (en) | 1978-01-19 | 1978-01-19 | Fungicidal 3-(n-acyl-n-arylamino)-gamma- butyrolactones, gamma-butyrothiolactones and gamma- butyrolactams |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1113385A true CA1113385A (en) | 1981-12-01 |
Family
ID=4110575
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA295,281A Expired CA1113385A (en) | 1978-01-19 | 1978-01-19 | Fungicidal 3-(n-acyl-n-arylamino)-gamma- butyrolactones, gamma-butyrothiolactones and gamma- butyrolactams |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1113385A (en) |
-
1978
- 1978-01-19 CA CA295,281A patent/CA1113385A/en not_active Expired
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