Note: Descriptions are shown in the official language in which they were submitted.
~75~ig~;
3-PHENYL-5-SUBSTITUTED-4(lH)-
PYRIDONES(THIONES)
This invention belongs to the field of agricul-
tural chemistry, and provides to the art new preemergence
and postemergence herbicides, and compositions and methods
of applying the compounds for the control of weeds. Since
the control of weeds is known to be a vital step in the
maximization of crop yields, herbicides are now established
as vital tools of the farmer and new and improved herbicidal
compounds are in constant demand.
Despite the great amount of research which has
been performed in the field of agricultural chemistry,
active compounds closely related to the compounds o formula
I herein have not been previously discovered. The poly-
halopyridones, which have two or more chlorine atoms as well
as other alkyl and halo substituents on the pyridine ring,
are known herbicides, but are obviously quite distinct from
the compounds of Eormula I.
The organic chemical art has explored the pyri-
dones rather extensively. For example, Ishibe et al., J.
Am. Chem. Soc. 9S, 3396-3397 (1973), disclosed a rear-
rangement of 3,5-diphenyl-1,2,6-trimethyl-4(lH)-pyridone.
Such compounds, however, are not herbicides. Leonard et
al., J. Am. Chem. Soc. 77, 1852-1855 (1955), taught the
synthesis of 3,5-dibenzyl-1-methyl-4(1H)-pyridones, which
compounds also have no herbicidal activity. The same
principal author also disclosed 3,5-di(substituted-ben-
zylidene)tetrahydro-4-pyridones, J. Am~ Chem. Soc. 79,
156-160 (1957~. These compounds also have no herbicidal
activity. --
;.
X-4097A -2-
~ .
.. . . . . .
75~96
.
Light et al., J. Org. Chem. 25, 538-546 (1960),
taught a number of 4-pyridone compounds including 2,6-
diphenyl-l-methyl-4(1H)-pyridone, and related compounds
bearing phenyl-ring substituents, none of which are her- ,
bicidally active.
An interesting recent article was published by
El-Kholy _ al. in J. Hetero. Chem. 10, 665-667 (published_ _ _
September 7, 1973). El-Kholy described a synthesis of 3,5-
diphenyl-l-methyl-4(lH)-pyridone and related compounds by
the reaction with methylamine of the sodium salt of 1,5-
dihydroxy-2,4-diphenyl-1,4-pentadien-3-one.
A series of novel 3-phenyl-4(lH)-pyridones-
(thiones) are herbicides which are active against an un-
usually wide range of weeds. New methods and compGsitions
for applying the compounds for the control of weeds, which
methods are particularly useful in cotton cropland, are also
disclosed. The novel compounds are of the general formula
X ~ ''',
.
R~
\~/ , ,
R
wherein: X is oxygen or sulfur;
R is Cl-C3 alkyl; Cl-C3 alkyl substituted with
halo, cyano~ carboxy or methoxycarbonyl; C2-C3
alkenyl; C2-C3 alkynyl; Cl-C3 alkoxy; acetoxy; or
dimethylamino; provided that R co~prises no more ~ ;
then 3 carbon atoms;
X-4097A -3-
-
~C~7S6~
the Rl groups independently are halo; Cl-C8
alkyl; Cl-C8 alkyl substituted with halo; Cl-C8
alkyl monosubstituted with phenyl, cyano or
Cl-C3 alkoxy; C2-C8 alkenyl; C2-C8 alkenyl
substituted with halo; C2-C~ alkynyl; C2-C8 alkynyl
substituted with halo; C3-C6 cycloalkyl; C4-C6
cycloalkenyl; C4-C8 cycloalkylalkyl; Cl-C3 alkanoyl-
oxy; Cl-C3 alkylsulfonyloxy; phenyl; phenyl mono-
substituted with halo, Cl-C3 alkyl, Cl-C3 a:Lkoxy,
or nitro; nitro; cyano; carboxy; hyd~oxy; Cl-C3
alkoxycarbonyl; -O-R ; -S-R3; -So-R3; or -SO2-R ; : ~
R is Cl-C12 alkyl; Cl-C12 alkyl substituted ::
with halo; Cl-C12 alkyl monosubstituted
with phenyl, cyano or Cl-C3 alkoxy; phenyl;
phenyl monosubstituted with halo, Cl-C3 ~: :
alkyl, Cl-C3 alkoxy or nitro; C3-C6 cycloalkyl; -
C4-C8 cycloalkylalkyl; C2-C12 alkenyl; C2-C12 :
alkenyl substituted with halo; C2-C12 alkynyl; ~.
or C2-C12 alkynyl substituted with halo; :
provided that R comprises no more than 12
carbon atoms; ~ .
R2 is halo; hydrogen; cyano; Cl-C3 al}coxycarbonyl;
Cl-C6 alkyl; Cl-C6 alkyl substituted with halo .
or Cl-C3 alkoxy; C2-C6 alkenyl; C2-C6 alkenyl
substituted with halo or Cl-C3 alkoxy; C2-C6
alkynyl; C3-C6 cycloalky1; C3-C6 cycloalkyl sub-
stituted with halo, Cl-C3 alkyl or Cl-C3 alkoxy;
C4-C6 cycloalkenyl; C4-C8 cycloalkylalkyl;
phenyl-Cl-C3 alkyl; furyl; naphthyl; thienyl;
-o-R4; -S-R ; -So-R4; -So2-R4~ or
X-4097A -4-
.
..
... : , -~:
~75~'36
\~ = aX R5
R4 is Cl-C3 alkyl; Cl-C3 alkyl substituted
with halo; C2-C3 alkenyl; C2-C3 alkenyl
substituted with halo; benzyl; phenyl; or
phenyl substituted with halo, Cl-C3 al]cyl : :
or Cl-C3 alkoxy;
the RS groups independently are halo;
Cl-C8 alkyl; C1-C8 alkyl substituted with ~:~
halo; Cl-C8 alkyl monosubstituted with phenyl, .
cyano or Cl-C3 alkoxy; C2-C8 alkenyl,
C2-C8 alkenyl substituted with halo; C2-C8 ~ :;
alkynyl; C2-C8 alkynyl substituted with halo,
C3-C6 cycloalkyl; C4-C6 cycloalkenyl; C4-C
: cycloalkylalkyl; Cl-C3 alkanoyloxy; C1-C3
alkylsulfonyloxy; phenyl; phenyl mono- :~
substituted with halo, Cl-C3 alkyl, Cl~C
alkoxy or nitro; nitro; cyano; carboxy;
hydroxy; Cl-C3 alkoxycarbonyl; -o-R6;
-S-R6; -SO-R6; or -SO2-R6; : .
. 1 12 lkyl; Cl C12 alkyl sub
stituted with halo; Cl-C12 alkyl mono-
substituted wi~h phenyl, cyano or Cl-C3
alkoxy; phenyl; phenyl monosubstituted
with halo, Cl-C3 alkyl, Cl-C3 alkoxy or
nitro; C3-C6 cycloalkyl; C4-C8 cyclo-
alkylalkyl; C2-C~2 alkenyl; C2-C12
X-4097A -5-
'
~C~7~6~6
alkenyl substituted with halo; C2-C12
alkynyl; or C2~C12 alkynyl substituted
with halo; provided that R6 comprises
no more than 12 carbon atoms;
m and n independently are 0, 1 or 2; provided that
when X is oxygen, R is methyl, and R2 is unsubstituted
phenyl, then m is 1 or 2;
and the acid addition salts thereof.
A preferred group of compounds are of the formula -
X
7 ~_~0 ¢ ~Rp
R
- `. .
wherein: X is oxygen or sulfur; ;
R is Cl-C3 alkyl; C2-C3 alkenyl; acetoxy;
20or methoxy;
q and p independently are 0, 1 or 2;
the R7 groups independently are halo; Cl-C3
alkyl; trifluoromethyl; or Cl-C3 alkoxy;
the R8 groups independently are halo; Cl-C
alkyl; trifluoromethyl; or Cl-C3 alkoxy; or two
R8 groups occupying adjacent o and _ positions
combine with the phenyl ring to which they are
attached to form a l-naphthyl group.
~ Another preferred group of compounds are of the
30 formula
X-4097A -6-
,
;
~7569~
-D/ \~__R2 III
N
R
wherein the various symbols are defined as before. The
most highly preferred compounds are those of formula III
wherein R is trifluoromethyl.
In the above formulae, the general chemical terms
are used in their normal meanings. For example, the terms
Cl-C3 alkyl, C2-C3 alkenyl, C2-C3 alkynyl, Cl-C3 alkoxy,
Cl-C8 alkyl, C2-C8 alkenyl, C2-C8 alkynyl, Cl-C6 alkyl,
C2-C6 alkenyl and C2-C6 alkynyl refer to such groups as
methyl, ethyl, isopropyl, vinyl, allyl, methoxy, isopropoxy,
propargyl, isobutyl, hexyl, octyl, l,l-dimethylpentyl, 2-
octenyl, pentyl, 3-hexynyl, 1-ethyl-2-hexenyl, 3-octynyl, ;
5-heptenyl, 1-propyl-3-butynyl and crotyl.
The terms C3-C6 cycloalkyl and C4-C6 cycloalkenyl
refer to such groups as cyclopropyl, cyclobutyl, cyclohexyl,
cyclobutenyl, cyclopentenyl and cyclohexadienyl.
The term C4-C8 cycloalkylalkyl refers to such
groups as cyclopropylmethyl, cyclobutylmethyl, cyclohexyl~
methyl and cyclohexylethyl.
The term Cl-C3 alkanoyloxy refers to groups such
as formyloxy, acetoxy and propionyloxy.
The term Cl-C3 alkoxycarbonyl refers to groups
such as methoxycarbonyl, ethoxycarbonyl and isopropoxy-
carbonyl.
'
X~4097A ~ -7_
,
', ~ .
.. .. . ... . .
1~756~
The term Cl-C3 alkylsulfonyloxy refers to
such groups as methylsulfonyloxy and propylsulfonyloxy.
The term halo refers to fluoro, chloro, bromo,
and iodo.
The compounds described above can form acid
addition salts, and such salts are useful embodiments of
the invention. The preferred salts are the hydrohalides
such as hydroiodides, hydrobromides, hydrochlorides and
hydrofl~orides. Salts of the sulfonic acids are also
particularly desirable. Such salts include sulfonates,
methylsulfonates and toluenesulfonates.
Although the above general description of the
compounds is believed to describe them unambiguousIy, a
group of exemplary compounds of formula I will be named
below to assure that the invention is understood by those
skilled in the art. Additional novel and useful compounds
generally falling within the scope of formula I are
described and claimed in copending Canadian application
Serial No. 305,980, filed June 22, 1978.
l~methyl-3,5-bis(3-methoxyphenyl)-4tlH~-
pyridinethione
l-ethyl-3-~4-ethoxyphenyl)-5--phenyl 4(1~)-
pyridinethione
3-(3,5-diiodophenyl) 5-(3-propylphenyl)-1-propyl-
4(lH)-pyridinethione
3-(2,6-dimethylphenyl)~l isopropyl-5-(1-naphthyl)
-4(lH)-pyridone
3-(4-methylphenyl)-5-phenyl-1-vinyl-4(1H)-
pyridone, hydroiodide
1-allyl-3-(3-chlorophenyl)-5 (2,3-diethoxyphenyl)
-4(lH)-pyridinethione
3,5-diphenyl-1-ethyl-4(lH)-pyridinethione
3-(3/5-difluorophenyl3-1-methoxy-5-phenyl-
-8-
,f
... ,. , .. ~ . .
~L~7S6~ ;
4(lH)-pyridone
l-acetoxy-3-(3,5-diethylphenyl)--5-(2,4-diethyl-
phenyl)-4(lH)-pyridinethione
l-allyl-3-(1-naphthyl)-5-(4-propoxyphenyl)~4(lH)-
pyridinethione
l-propyl-3-(4-trifluoromethylphenyl)-5-(3-
trifluoromethylphenyl)-4(1H)-pyridone
3-(2,6-difluorophenyl)-5-(3-iodophenyl)~
vinyl-4(lH)-pyridone
3-(3,5-dibromophenyl)-5-(3-isopropoxyphenyl)-1- :
propyl-4(lH)-pyridone ::
l-methyl-3-phenyl-S-(2-propylphenyl)-4(lH)-
pyridinethione, hydrochloride
3-(3-bromophenyl)-1-methyl-5-phenyl-4(1~
pyridone .
3-(4-chlorophenyl)-5-(2,4-dimethoxyphenyl)--1-
propyl-4(lH)-pyridone .
l-allyl-3-phenyl-5-(3-trifluoromethylphenyl)-
4(lH)-pyridinethione
1-acetoxy-3,5-diphenyl-4(lH)-pyridinethione -
3-(2-iodophenyl)-5-(3-isopropylphenyl)-1-methoxy-
4(1H)-pyridinethione
3-(2-iodo~4-methylphenyl)-5-phenyl-1-vinyl-
4(lH)-pyridinethione
l-acetoxy-3-(4-chlorophenyl)-5-(1-naphthyl)-
4tlH)-pyridone
3,5-diphenyl-1-isopropyl-4(lH)-pyridinethione
3-(3-bromo-5-ethylph~nyl)-5-(3-methylphenyl~-
l-propyl-4(1H)-pyridinethione ..
', ' ~
X-4097A -9-
: . ...
. :.
.. ..
~7~ 96
3-(4-ethoxy-2-fluorophenyl)-1-methoxy-5-phenyl-
4(1H)-pyrldone
l-allyl-3,5-bis(3-ethyl-4-methoxyphenyl)-4(1H)-
pyridone
3-(2-iodo-4-propylphenyl)-1-methyl-5-~4-trifluoro-
methylphenyl)-4(lH)-pyridinethion~
l-methyl-3-(3-methyl-5-propylphenyl)-5-phenyl-
4(lH)-pyridinethione
3-(2-chloro-4-iodophenyl)-5-(3-fluorophenyl)-1-
propyl-4(lH)-pyridinethione
3-(3-chlorophenyl)-5-[2,4-bis(trifluoromethyl)-
phenyl]-l-methoxy-4(lH)-pyridone
3-benzyloxy-1-chloromethyl-5-(3-ethynylphenyl)-
4(lH)-pyridone
3-benzylthio-1-(2-bromoethyl)-5-(2,4-dimethyl-
phenyl)-4(lH)-pyridone
3-benzylsulfinyl-1-ethyl-5-(3-fluoro-5-propyl-
phenyl)-4(lH)-pyridone
3-benzylsulfonyl-5-~3-octyIphenyl)-l-propyl~
4(lH)-pyridone
3-(2-butylphenyl)-1-trifluoromethyl-4(lH)-
pyridone, hydrobromide
1-(2-chloroethyl)-3-cyano-5-phenyl-4~1H)-pyridine~
thione
3-(3-hexylphenyl~ methyl-5-(2-methylphenyl)-
4(1H)-pyridone '
1-~3,3-dibromopropyl)-3-~2,4-dichlorophenyl)-
5-methyl-4(lH)-pyridone
3-(2,4-dimethylphenyl)-5-methoxycarbonyl-1- -~
: 30 methyl-4(lH)-pyridone
X-4097A -10-
- ,,
.~ '
~ . ~ , : , . , ., : . . : : . .
~7~696
l-m~thyl-3-13-(1-propylpentyl)phenyl]-5-propyl-
4(111)-pyridon~
1-(2-cyanoethyl) 3-(3-octyl-4-methylphenyl)-5-
propoxycarbonyl-4(lH)-pyridone
3-[3-(2-ethylpentyl)phenyl]-1-carboxymethyl-5-
(3-trifluoromethylphenyl)-4(lE~j-pyridone
3-(2-chloromethylphenyl)-1-methoxycarbonylmethyl-
4(lH)-pyridone
3,5-diphenyl-1-ethynyl-4(lH)-pyridinethione
3-(4-heptafluoropropylphenyl)-5-hexyl-1-methyl-
4(lH)-pyridinethione :
3-(3,5-diethylphenyl)-1-propargyl-5-[3-(5,5-
dibromopentyl)phenyl]-4(lH)-pyridone
3-(2,4-dipropylphenyl)-1-methyl-5-triEluoro-
methyl-4(lH)-pyridone ~:
3-(4-benzylphenyl)-1-ethoxy-5-(2-fluoroethyl)-
4(lH)-pyridone
3-(2-chloroethy~)-5-[4-(2,2-diiodooctyl)phenyl]- -
l-methoxy-4(lH)-pyridinethione
3-(3-chloro-2-methoxyphenyl)-5-(1,1-dibromo-
pentyl)-l-methyl-4(lH)-pyridone
3-(6-iodohexyl)-1-isopropoxy-5-phenyl-4(1H)-
pyridinethione
3-(3-hexylphenylj-5-methoxymethyl-1-methyl-
4(lH)-pyridone
l-dimethylamino-3,5-bis(3-tri~luoromethylphenyl)- -:
4(lHj-pyridinethione ~ -
l-methyl-3-[4-(4-phenylhexyl)phenyl]-5-(3-
propylphenyl)-4(lH)-pyri.done
,
X-4097A -11-
, . ~. . .
1~756g6
1-(2-chloroethyl)-3-[4-(2-cyanoethyl)phenyl]-
4(1H)-pyridinethione
l-methyl-3-(2-propoxyethyl)-5-phenyl-4(lH)-
pyridinethione, hydrofluoride
3-(6-ethoxyhexyl)-5-(3-ethyl-5-iodophenyl)-1-
(3-iodopropyl) 4(lH)-pyridone
l-methyl-3-phenyl-5-vinyl-4(lH)-pyridinethione
3-allyl-5-[4-t3-cyanohexyl)phenyl]-1-propoxy-
4(lH)-pyridinethione
103-[4-(8-cyanooctyl~phenyl] 1-methyl-5-~2-pen-
tenyl)-4(lH)-pyridone
3-(3-hexenyl)-5-[2-(2-methoxyethyl)phenyl]-1-
methyl-4(lH)-pyridinethione
3-(2,2-dichlorovinyl)-1-methyl-5-[3-(3-propoxy-
heptyl)phenyl]-4(lH)-pyridone
3-(2-bromo-1-butenyl)-5-13-(6-ethoxyheptyl)-
phenyl]-l-ethoxy-4(lH)-pyridone .
3-(2-iodo-1-hexenyl)-1-methyl-5-(3-vinylphenyl)-
4(lH)-pyridinethione
203-(4-allylphenyl)-1-dimethylamino-5-phenyl
4(lH)-pyridinethione
3-(2-methoxyallyl)-1-methyl-5-(4-trifluoromethyl-
phenyl)-4(lH)-pyridinethione : ~:
3-(4-etlloxy-2-pentenyl)-5-[2-(2,4-hexadienyl)- . .
phenyl]-l-methoxy-4(lH)-pyridone . : :
: l-methoxycarbonylmethyl-3-[3-(3-octenyl)phenyl]-
5-phenyl-4(lH)-pyridone, methanesulfonate
3-[3-(2-hexenyl)phenyll-1-methyl-5-(3-propyl-
phenyl)-4(1H)-pyridinethione
X-4097A -12-
'
7 5 69 6
3-(2-ethyl-3-~luorophenyl)-5-ethynyl-1-methyl-
4(llI)-pyridinethione
3-(2-butynyl)-5-(2,4-diiodophenyl)-1-ethoxy-
4(lH)-pyridone
3-[~-(2,6-dibromo-2-heptenyl)phenyl]-1,5-di-
methyl-4(lH)-pyridone
3-(2-hexenyl)-1-methyl-5-[3-(1,1,2,2-tetrachloro-
4-octenyl)phenyl]-4(lH)-pyridone
3-cyclopropyl-5-[2-(2-fluoro-1-pentenyl)phenyl~-
1-methoxy-4(lH)-pyridinethione
3-cyclobutyl-5-[4-(2-iodovinyl)phenyl]-1-propoxy-
4(lH)-pyridone
3-cyclohexyl-5-(3-ethynylphenyl)-1-iodomethyl-
4tlH)-pyridinethione .
l-(l-carboxyethyl)-3-(2-chlorocyclopropyl~-~5- .
[3-(3-chloropropargyl)phenyl]-4(lH)-pyridone
3-(2,2-dibromocyclohexyl)-1-methyl-5-12-(3-
pentynyl)phenyl-4~lH)-pyridinethione :
3-[4-(1,1-dibromo-4-pentynyl)phenyl]-1-isopro- .~
20 poxy-5-(2-methylcyclobutyl)-4(lH)-pyridone : -
3-(2,4-diiodocyclopentyl)-1-ethyl-5-[4-(2-
octynyl)phenyl]-4(lH)-pyridone
l-acetoxy-3-(4-propylcyclohexyl~-5-[3-(6,6,6-
trifluoro-2-hexynyl)phenyl]-4(lH)-pyr.idinethione
~ 3-[3-(4-octynyl)phenyl]-5-(2-methoxycyclopropyl)~
l-methyl-4(lH)-pyridinethione -~:
3-[Z-(l,l-dichloro-4-heptynyl)phenyl]-5-(4- ::
methoxycyclohexyl)-l-methoxy-4(lH)-pyridone
3-(4-cyclopropylphenyl)-1-(2-methoxycarbonyl-
methyl)-5-(2-propoxycyclobutyl)-4(lH)-pyridinethione
X-4097A -13-
' .
.
569~ii
3-(2-cyclobutenyl)-5-(3-cyclopentylphenyl)-1-
ethoxy-4(lH)-pyridinethione
3-(3-cyclohexenyl) 5-(3-cyclohexylphenyl)~l-
dimethyl~mino-4(lH)-pyridone
3-14-(1-cyclobutenyl)phenyl]~5--methoxy-1-vinyl-
4(lH)-pyridone, toluenesulfonate
3-chloromethoxy-1-cyanomethyl-5-(2-formyloxy-
phenyl)-4(lH)-pyridinethione
1-(2-carboxyethyl)-3-(3-propionyloxyphenyl)-5-
trifluoromethoxy-4(1H)-pyridinethione
3-l4-(2-cyclohexenyl)phenyl~-5-isopropoxy-1-
trifluoromethyl-4(lH)-pyridone
3-(1,2-dibromopropoxy)-1-ethoxy-5-(2-methyl-
sulfonyloxyphenyl)-4(lH)-pyridinethione
l-dichloromethyl-3-(2-iodoethoxy)-5-(4-isopropyl~
sulfonyloxyphenyl)-4(1H)-pyridone
3-(3-biphenylyl)-1-methyl-5-vinyloxy-4(lH)-- :
pyridinethione ::
3-allyloxy-5-[4-(2-chlorophenyl)phenyl]-1-
20 isopropyl-4(1H)-pyridone, hydrochloride -;
3-(2,2-dichlorovinyloxy)-5-[2-(3-iodophenyl)~
phenyl]-l-methyl-4(lH)-pyridone i~
3-(2-bromoallyloxy)-5-[3-(3-bromophenyl)phenyl]-
l-vinyl-4(lH)-pyridone
l-allyl-3-[4-(2-methylphenyl)phenyl]-5-(3,3,3-
trifluoro-l-propenyloxy)-4(lH)-pyridone
: l-methoxy-3~phenoxy-5-[3-(4-propylphenyl)phenyl]- ..
4(lH)-pyridone
3-~2-chlorophenoxy)-5-~4-methoxyphenyl)phenyl]~
3~ l~propargyI-4(1H)-pyridone
: X-4097A -14-
' ..
'
:
, ~ . ~ .: . . . ::
` ~75696
3-(4-bromophenoxy)-5-[4-(2-ethoxyphenyl)phenyl]-
l-ethyl-4(lH)-pyridone
3-(2-iodophenoxy)-5-[3-(4-isopropoxyphenyl)-
phenyl]-l-methoxycarbonylmethyl-4(lH)-pyridone
1-cyanomethyl-3-(2-methylphenoxy)-5-[3-(4-nitro-
phenyl)phenyl]-4(lH)-pyridinethione
l-methyl-3-(4-nitrophenyl)-5-(3-propylphenoxy~-
4(lH)-pyridone
3-(4-cyanophenyl)-1-ethoxy-5-(2-methoxyphenoxy)-
4(lH)-pyridone
3-(3-carboxyphenyl)-5-(2-ethoxyphenoxy)-1-
isopropyl-4(lH)-pyridone, hydrofluoride :
1-(2-carboxyethyl)-3-(4-hydroxyphenyl)-5-(3~ .
propoxyphenoxy) 4(lH)-pyridone
3-benzyl-5-(2-methoxycarbonylphenyl)~
methyl-4(lH)-pyridone
l-dimethylamino-3-(3-phenylpropyl)-5-(4-propoxy-
carbonylphenyl)-4tlH)-pyridone
3-(3-butoxyphenyl)-5-(2-furyl)-1-trifluoromethyl-
20 4(lH)-pyridone :~; :
3-(1-ethylpentyl)-5-(3-furyl)-1-methyl-4(lH)~
pyridone
3-[4-(2-propylhexyloxy)phenyl]-1-methoxycarbonyl- ;:
methyl-5-(2-thienyl)-4(lH)-pyridone ::
l-methyl-3-(4-nonyloxyphenyl)-5-(3-thienyl)- ~:
4(lH) pyridinethione
l-methyl-3-[4-(2-propylnonyloxy)phenyl]-5-
(4-trifluoromethylphenyl)-4(1~)-pyridinethione
3-(3,5-diethylphenyl~-1-ethyl-5-(4-trifluoro-
30 methoxyphenyl)-4(1H)-pyridinethione ~;
X-4097A -15-
s~
3-(2,4-divinylphenyl)-5-[4-(2-~luoroetho~y)-
phenyl]-1-isopropoxy-4(1~1)-pyridinethione
3-[3-(5,5-dibromopentoxy)phenyl]-5-(3,5-dicyclo-
propylphenyl)-l-ethyl~4(lH)-pyridone
3-(2,4-dimethoxyphenyl)-1-(2-methoxycarbonyl-
methyl)-5-[2-(12-iodododecyloxy)phenyl]-4(lH)-pyridinethione
3 (4-benzyloxyphenyl)-1-cyanomethyl-5-[3,5-di-
(isopropenyl)phenyl]-4(lH)-pyridinethione
3-(2,6-dinitrophenyl)-1-methoxy-5-[5-phenyl- : :
10 pentoxy)phenyl]-4(lH)-pyridone -:
3-(2,4-diformyloxyphenyl)-1-ethoxy-5-[4-(3-
phenylhe~yloxy~phenyl]-4(1H) pyridinethione
3-[4-(3-cyanopropoxy)phenyl]-5-(3-ethoxy-5-
iodophenyl)-l-methyl-4(lH)-pyridinethione
3-[4-(7-cyanoheptyloxy)phenyl]-1-ethyl-5-phenyl-
4(1H)-pyridinethione
3-[3-(4-cyanoundecyloxy)phenyl]-5-[2,4-di(2-
ethoxyethyl)phenyl]-l-methoxy-4(lH)-pyridinethione
3-[2-(2-ethoxyethoxy)phenyl]-1-(2-iodoe~hyl)-
5-(3,4-diacetoxyphenyl~-4(lH)-pyridinethione
3-(4-butoxy-2-difluoromethylphenyl)-1-cyano-
methyl-5-[3-(6-methoxyhexyloxy)phenyl]-4(lH)-pyridone
3-(2-cyclohexyl-4-ethylphenyl)-1-methoxycarbonyl-
methyl-5-[2-16-propoxynonyloxy)phenyl]-4(lH)-pyridone : :
3-~2,4-di~2-pentynyl3phenyl]-1-isopropoxy-5-
(2-vinyloxyphenyl)-4(lH)-pyridinethione
3-(2,4-diallyloxyphenyl)-1-(2,2-dichloropropyl)-
5-(2-methyl-6-nitrophenyl?-4(lH)-pyridone
3-13-(2,4-hexadienyloxy)phenyl]-1-isopropyl-5-
phenyl-4(lH)-pyridinethione, hydroiodide
X-409~A -16-
~75~9~
l-(2-carboxyethyl)-3-(2,6-d`ipropylphenyl)-5-
[4-(5-dodecenyloxy)phenyl~-~(lH)-pyridinethione
3-[2-(2-chloroallyloxy)phenyl]-l-(2,2-dichloro-
ethyl)-5-(2,~-diethoxyphenyl)-4(l~)-pyridinethione
l-allyl-3-(4-cyano-3-e~hoxycarbonylphenyl)-5-
[4-(4,4,4-tri~luoro-2-butenyloxy)phenyl]-4~l~)-pyridone
l-chloromethyl-3-(3-methylsulfonyloxy-5-vinyl-
phenyl)-5-[3-(2,2-dibromo-3-hep~enyloxy)phenyl]-~(lH)- :
. : .
pyridinethione ,~'.
l-ethoxy-3-[3-~9-iodo-l-nonenyloxy)phenyl]-5-
phenyl-4(lH)-pyridone ,~
l-chlorodifluoromethyl-3-[2,4-di(,chloromethyl)-
phenyl]-5-[2-(l,2,3-trichloro-6-dodecenyloxy)phenyl]-
4(lH)-pyridinethione '
3-[3-(4-chloro-2-butynyloxy)phenyl]-l-ethoxy-5-
(3-fluoro-4-isobutoxyphenyl)-4(,lH)-pyridone
3-[3-~6,6-dibromo-3-(hexynyloxy)phenyl]-l-
methyl-5-(3-nitro-4-propylphenyl)-4(,lH)-pyridinethione :
l-acetoxy-3-(2,4-dibromophenyl)-5-[3-(l,l,2,2- ,:
tetrafluoro-3-decynyloxy)phenyl]-4(lH)-pyridone
3-(3-ethynyloxyphenyl)-l-methyl-5-phenyl-4(lH)- '
pyridinethione, hydrobromide
3-[2-(10-dodecynyloxy~phenyl]-l-methyI-5-(2-
propyl-4-propylsulfonyloxyphenyl)-4(lH)-pyridone
3-~2,4-di(3-pentenyl)phenyl]-5-(3-phenoxyphenyl)-
l-~l,l,2,2-tetrafluoroethyl~-4(l~)-pyridone
3-~4-(4-fluorophenoxy)phenyl]-l-isopropyl-5-
phenyl~4(lH)-pyridinethione :
X-4097A -17- :
.
.
~L~75696
1-(3~chloropropyl)-3-(3-cyanomethyl-5-ethyl-
phenyl)-5-13-(3-iodophenoxy)phenyl]-4(lH)-pyridone
3-~3-octyl-5-fluorophenyl~-5-[2-(3-ethylphenoxy)- :
phenyl]-l-trifluoromethyl-4(1H)-pyridone
3-(2-ethyl-4-propylsulfonyloxyphenyl)-1 ethynyl-
5-[2-(4-isopropylphenoxy)phenyl~-4(1H)-pyridone
l-carboxymethyl-3-(2,4-dinonyloxyphenyl)-5-[3-
(4-methoxyphenoxy)phenyl~-4(lH)-pyridone
l-chloromethyl-3-(2,4-difluorophenyl)-5-[2-(3-
propoxyphenoxy)phenyl]-4(lH)-pyridinethione
l-methyl-3-[4-(2-nitrophenoxy)phenyl]-5-phenyl- :
4(lH)-pyridinethione
3-(3-isobutylthiophenyl)-1-isopropyl-5-phenyl-
4(lH)-pyridinethione
3-(3-chloro-4-heptylthiophenyl)-5-[3-(4-cyano-
pentyl)phenyl]-l-methyl-4(1H)-pyridone
l-methyl-3-phenyl-5-[2-(3-ethylhexylthio)phenyl]-
4(lH)-pyridone, hydrofluoride ~ :
3-(2-chloro-4-ethylphenyl)-1-ethyl-5-(3-nonyl-
thio-4-vinylphenyl)-4(lH)-pyridone
l-ethynyl-3-phenyl-5-E3-(2-ethylpentylthio~-
phenyl~-4(lH)-pyridone ~;
1-(2-methoxycarbonylmethyl)-3-[4-(3-iodophenyl)-
phenyll-5-(3-trifluoromethylthiophenyl)-4(lH)-pyridinethione ~ ~
. l-acPtoxy-3-(3-cyclopentylphenyl~-5-E3-(2- -
1uoroethylthio)phenyl]-4(1H)-pyridinethione
3-(2-cyano-4-hydroxyphenyl)-1-dimethylamino-5
~3-~5,5-dlbromopentylthio)-4-nitrophenyl]-4(1H)-pyridone :
X-4097A -18-
.
.: :
.
~756g~
3-~4-(4,4-diiodododecylthio)phenyl)-1-methyl-5-
phenyl-4(lH)-pyridone
' 3-(3-benzylthio-5-ethynylphenyl)-1-cyanomethyl-
5-(2-hexylphenyl)-4(lH)-pyridinethione
3-[3,5-bis(4-phenylbutylthio)phenyl]-5-(2-
methylphenyl)-l-(1,1,2,2-tetrafluoroethy:L~-4(lH)-pyridone
3-[2-bromo-4-(6-phenylhexylthio)phenyl]-5-[4-
(2-cyanopropylthio)-2-ethylphenyl]-1-methyl-4(1H)-pyridine-
thione
3-[4-(6-cyanoheptylthio)phenyl]-1-fluoromethyl-
4(lH)-pyridone
3-(3-acetoxy-5-ethylphenyl)-5 [2-(8-cyanoundecyl- :
thio)phenyl]-l-chlorodifluoromethyl-4(lH)-pyridone
3-(~-benzyl-2-ethoxyethoxyphenyl)-1-(2-carboxy-
ethyl)-5-[3-(2-ethoxyethoxy)-5-propargylphenyl]-4(1H)-
pyridone, toluenesulfonate
1-ethyl-3-14-(6-methoxyhexylthio)phenyl]-5-
phenyl-4(lH)-pyridinethione
l~isopropenyl-3-[3-(3-phenylpentyl)phenyl]-5-
[4-(6-isopropoxynonylthio)phenyl]-4(lH)-pyridone
3-(2-cyanomethyl-4-vinylthiophenyl)-1-ethyl-5-
[2-(7-phenylheptyl~phenyl]-4(lH)-pyridone
3-(3-a~lylthio-4-methoxymethylphenyl)-5-[2-
(6-cyanohexyl)-4 vinylphenyl]-1-methyl-4(1H)-pyridone
l~methoxycarbonylmethyl-3-[3-(2-pentenylthio)-
phenyl]-5-phenyl-4(lH)-pyridinethione
3-~3-(2-decenylthio)-5-~2,4-hexadienyl)phenyl]-
1-ethoxy-5-phenyl-4(lH)-py~idone
',
,~
X-4097A ~ -19-
.:
- , . . , :
756~6
3-[4~ ~dichloroallylthio)phenyll 5-l3-(4-
octenyl)-2-propylphenyl]-1-trifluoromethyl-4~1~l) pyridone
3-(4-carboxy-2-hydroxyphenyl)-5-[3-(2-chloro-
3-butenylthio)-5-nitrophenyl]-1-vinyl-4(1H)-pyridone
3-[4-(5,5-dibromo-3-heptenylthio)phenyl]-1-
methyl-5-phenyl-4(lH)-pyridone
3,5-bis[4-(9-iodo-8-nonenylthio)phenyl~-1-
isopropyl-4(lH)-pyridinethione
l-ethyl-3-(3-fluorophenyl)-5-[4-(12,12,12-tri-
. 10 chloro-2,6-dodecadienylthio)phenyl]-4(lH)-pyridinethione
3-[2-(1-chloropropargylthio)phenyl]-1-dimethyl- : ~ :
amino-5- E3- (4-pentenyl)-5-methoxycarbonylphenyl]-4(1H)-
pyridone
3-14-(3,3-dibromo-5-hexynylthio)phenyl]-1-
methoxy-5-phenyl-4(lH)-pyridone
1-(2-chloropropyl)-3-[2-cyclopropyl-4-(1,1,2,2-
tetrafluoro-5-decynylthio)phenyl]-5-phenyl-4(lH)-pyridine-
thione :
l-acetoxy-3-(3-ethynylthiophenyl)-5-(3-ethynyl- .
5-fluorophenyl)-4(lH)-pyridone
3-14-(4-decynylthio)-2-methylphenyl]-1-ethoxy- :
5-(5-fluoro-3-trifluoromethylphenyl)-4(lH)-pyridinethione ~
l-cyanomethyl-3-(4-phenylthiophenyl)-5-phenyl- : .
4(1H)-pyridinethione, hydrochloride :.
3-(3-chlorophenyl)-5-12~(3-fluorophenylthio)-
phenyl]-l-methyl-4(lH)-pyridone : : .
carboxymethyl-3-[3-(2-iodophenylthio)phenyl]-
` 5-(3-methyl-5-methoxycarbo~ylphenyl)-4~lH)-pyridone ~ :
: 1-(2-chloroethyl~-3-(2,4-diethylphenyl)-5- -:
[4-(4-ethylphenylthio~-2-methoxyphenyl]-4(1H)-pyridone :~
: X-4097A ; ` . -20-
: ' , . ~: .
: .
: ~
... . . , . - , ,,, .. ,. ,." . .... .. . . .. . . . . . . ....
9~ii
3-~3-(3-isopropylphenylthio)phenyl]-5-phenyl-
1-trifluoromethyl-4(lH)-pyridone
l-acetoxy-3-(4-butylphenyl)-5~[4-(3-methoxy-
phenylthio)phenyl]- 4(lH)-pyridinethione
3-(2-methyl-6-propoxyphenyl)-3-[4-(3-propoxy-
phenylthio)phenyl]-l-propargyl-4(1H)-pyr:idone
3-[3-chloro-5-(4-nitrophenylthio)phenyl]-1-
methyl-5-(2,4-divinylphenyl)-4(lH)-pyridone
3-(4-butylsulfinylphenyl)-5-phenyl-1-propargyl-
4(lH)-pyridone
l-ethyl-3-(3-heptylsulfinylphenyl)-5-(4-propoxy-
carbonylphenyl)-4(lH)-pyridone
3-(2-carboxyphenyl)-1-dimethylamino-5-[2-hydroxy-
4-(2-propylpentylsulfinyl)phenyl]-4(lH)-pyridinethione
l-acetoxy-3-(2-cyano-5-nonylsulfinylphenyl) 5-
(3,5-dinitrophenyl)-4(lH)-pyridinethione
l-ethoxy-3-[3-(4-propylnonylsulfinyl)phenyll-5-
phenyl-4(lH)-pyridone
l-methoxy-3-(2-nitrophenyl?-5-(4-trifluoromethyl-
sulfinylphenyl)-4(lH)-pyridinethione
3-(2-ethoxyphenyl)-1-isopropyl-5-14-(2-fluoro-
ethylsulfinyl)-2-isopropylphenyl~-4(lH)-pyridone
3-13,5-di(4-chlorophenyl)phenyl]-3-14~(5,5- :
dibromopentylsulfinyl-2-ethoxyphenyl]-1-ethynyl-4(lH)~
pyridone `~
3-[3-(12-iodododecylsulfinyl)phenyll-5-phenyl-
l-propargyl-4~lH)-pyridone, hydroiodide ~:
3-(4-benæylsulfinylphenyl~-5-(3-biphenylyl)-1-
isopropenyl-4(1H?-pyridone
. ` ,
X-4097A -21-
-- 1~7Si~9~i
3-[3,5-di(methylsulfonyloxy)phenyl]-5-[3-(5-
phenylpentylsulfinyl)phenyl]-l-vinyl-4(1H)-pyridone
3-[2-(3-cyanopropylsulfinyl)phenyl]-1-methoxy-
carbonylmethyl-5-phenyl-4(lH)-pyridineth:ione
3-(3-acetoxyphenyl)-5-[2-(7-cyanoheptylsulfinyl)-
phenyl]-l-methoxycarbonylmethyl 4(1H)-pyridone
1-(2-carboxyethyl)-3-[3-(3-cyc:Lohexenyl)-5-
(3-cyanoundecenylsulfinyl)phenyl]-4(lH)-pyridone
3-(2-chloro-4-cyclohexylphenylj-5-[3-chloro-5-
(2-ethoxyethylsulfinyl)phenyl]-1-(2-cyanoethyl)-4(1H)-
pyridinethione
1-(2-chloroethyl)-3-[4-(6-methoxyhexylsulfinyl)-
phenyl]-4(1H)-pyridone
3-(4 cyclopropylphenyl)-1-iodomethyl-5-[3-(6-
propoxynonylsulfinyl)phenyl~-4(lH)-pyridone
3-E3-(2-chloro-~-undecynylsulfinyl)phenyl~
(2,2-dibromoethyl)-5-t2-ethyl-5-vinylsulfinylphenyl)-4(lH)-
pyridinethione - :
3-[3,5-di(allylsulfinyl)phenyl]-5-phenyl-1- : :
propyl-4(lH)-pyridone, hydrofluQride
3-[3-(2,4-hexadienylsulfinyl)phenyl]-1-methyl-5-
phenyl-4(lH)-pyridinethione ~
l-dimethylamino-3-[2-(5-dodecenylsulfinyllphenyl]- -
5-(3-isobutylphenyl~-4(lH)-pyridone
l-acetoxy-3-[4-(2-bromoallylsulfinyl?phenyl]-
5-(2,4 dimethylphenyl)-4(lH)-pyridinethione
l-ethoxy-3-(3-iodo-4-pentylphenyl~-5-~3-~3,3,4,4- ~:
tetrafluoro-1-butenylsulfinyl)-5-hexylphenyl]-4(1H)-pyridone
': ~ '
X-4097A -22-
- . . . . . . . . . . .. ..
' ' . ' : . ' ,: , . . .
11 ~)756~6
l-isopropoxy-3-phenyl-5-[4-(1,1,2-trichloro-3-
heptenylsulfinyl)phenyl]-4(lH)~pyridinethione
3-~4-t9-bromo-4-nonenylsulfinyl)phenyll-5-[2-
(3-ethylhexyl)phenyl]-1-ethynyl-4(1H)-pyridinethione
3-[2,4-di(chlorodifluoromethyl)phenyl]-1-propargyl-
5-[3-(1,2,3-triiodo-6-dodecenylsulfinyl)phenyl]-4(lH)-
pyridone
3-[3-(4-bromo-2-butynylsulfinyl)-5-methylphenyl]-
5-[2-iodo-3-(1,2,3-trichloropentyl)phenyl]-1-vinyl-4(lH)-
pyridone
l-allyl-3-~2-(2,2-dibromo-4-hexynylsulfinyl)-
phenyl]-5-phenyl-4(lH)-pyridone
l-methoxycarbonylmethyl-3-[3-ethyl-5-(9,9,10,10-
tetrafluoro-2-decynylsulfinyl)phenyl]-5-phenyl-4(lH)-
pyridinethione
3-(4-benzyl-2-bromophenyl)-1-(2-carboxyethyl)-
5-[3 (1-chlorobutyl)-~5-(6-dodecynylsulfinyl)phenyl]-4(lH)- .
pyridone
1-~2-cyanoethyl)-3-(4-phenylsulfinylphenyl)-5-
phenyl-4(lH)-pyridinethione
l-cyanomethyl-3-[4-(3-fluorophenylsulfinyl)phenyl]-
5-[3-~4-octenyl)phenyl]-4(lH)-pyridone
l-chloromethyl-3-[3-(1,1-dichloro-4-octenyl)-
4-nitrophenyl~-5-[3-(2-iodophenylsulfinyl)phenyl]-4(lH)-
pyridone
3-[3-(2-chlorovinyl)-5-(4-methylphenylsulfinyl~-
phenyl]-l-ethoxy-5-~3-(8-iodo-4-octenyl)phenyl~-4(lH)-
pyridone :
3-[4-(3-isopropylphenylsuIfinyl)phenyl]-5-phenyl-
1-propyl-4(1H)-pyridone
X-4097~ -23-
'
~L~756~6
3-[3-(2-ethoxyphenylsulfinyl)phenyl]-l--methyl-
5-[4-(2-propoxyphenoxy)phenyl]-4(lH)-pyr:idone
3-[4-(2,4-cyclohexadienyl)-3-f:Luorophenyl]-l-
ethyl-5-[3-hydroxy-5-(3-nitrophenylsulfinyl)phenyl]-4(lH)-
pyridinethione
l-methyl-3-(4-methylsulfonylphenyl)-5-phenyl-4(lH)-
pyridinethione
l-ethyl-3-(3-hexylsulfonylphenyl)-5-(4-hydroxy~
phenyl)-4(lH)-pyridone
3-(2-carboxy-4-ethylphenyl)-l-dimethylamino-5-
[4-(3-ethylheptylsulfonyl)phenyl]-4(lH)-pyridone ~-
l-acetoxy-3-(2-hexyl-5-~luorophenyl)-5-(3-nitro-
5-nonylsulfonylphenyl)-4(lH)-pyridone ~ :
3-phenyl-l-propoxy-5-[2-(3-propylnonylsulfonyl)-
phenyl]-4(lH)-pyridone
l-ethoxy-3-phenyl-5-(3-trifluoromethyl-5-tri- ~:
fluoromethylsulfonylphenyl)-4(lH)-pyridone
3-[4-(2-chloroethylsulfonyl)phenyl]-5-(3-
fluoro 4-octylphenyl)-1-methoxy-4(lH)-pyridinethione
3-(3-bromo-5-nitrophenyl)-l-ethynyl-5-[4-
cyano-2-(6,6-dibromohexylsulfonyl)phenyl]-4(lH)-pyridone
3-[3-(4,4-diiodododecylsulfonyl)phenyl~-5-(2- ~:~
naphthyl)-l-(l-propynyl)-4(lH)-pyridone
3-(4-benzylsulfonylphenyl)-5-~3-(2-ethoxy-
phenyl)phenyl]-l-isopropenyl-4(lH~-pyridinethione
3-[5-chloromethyl-4-(2-propylphenyl)phenyl]-l- :
vinyl-5-~4-(3-phenylbutylsul~onyl)phenyl]-4(lH~-pyridone
3-~3-(3-cyanopropylsulfonyl)phenyl]-l-methoxy-
carbonylmethyI-5-phenyl-4(lH)-pyridone
'., .' .
X-4097A -24-
.: . - : :
~L~7~i6~6
1-(2-carboxyethyl)-3-[4-(7-cyanoheptylsulfonyl)-
phenyl]-5-[3-(4-chlorophenyl)phenyl]-4(1H)-pyridone
l-cyanomethyl-3-[3-(11-cyanoundecylsulfonyl)-5-
fluorophenyl]-5-(4-propylsulfonyloxyphenyl)-4(lH)-pyridone
3-(2-acetoxy-4-ethoxyethylsulfonylphenyl)-1-
chloromethyl-5-(5-cyclopropyl-2-trifluoromethylphenyl~-
4(lH)-pyridone
3-(3-ethoxyhexylsulfonylphenyl)-5-phenyl-1-
trifluoromethyl-4(1H)-pyridinethione
3-[4-(3~cyclohexenyl)phenyl~-1-propyl-5-[3-(9-
propoxynonylsulfonyl)phenyl]-4(lH)-pyridone
3-[3-cyanomethyl-4-(1-cyclobutenyl~phenyl]~l-
methyl-5-(4-vinylsulfonylphenyl)-4(1H)-pyridinethione ~:.
3-(2-allylsulfonyl 4-chlorophenyl)-5-(2-allyl-
3-cyclohexylphenyl)-1-dimethylamino-4(lH)-pyridinethione
l-acetoxy-3-~4-(2,3-hexadienylsulfonyl)phenyl]-
5-phenyl-4(lH)-pyridone
3,5-bis[3-(4-decenylsulfonyl)phenyl]-1-methoxy-
4(lH)-pyridone :~
3-[4-(2-bromoallylsulfonyl)-2-methylphanyl]-1-
methyl-5-[3-(7,7,8,8-tetrafluoro-2-octynyl)phenyl]-4(1H)
pyridone
3-[4-(6-heptynyl)-3-methylphenyl]-1-ethyl-5-
~3-(1,1,2-triiodo-3-butenylsulfonyl)-5-chlorophenyl~-4(1H~-
pyridone
3-[2-(5,5-dibromo-2-pentynyl)phenyl]-1-di~lethyl-
amino-5-~3-~5-fluoro-2-nonenylsulfonyl)phenyl]-4(1H~--
pyridone
X-4097A -25-
~7~6~6
l-acetoxy-3-[2-ethyl-4-(5-methoxypentyl)phenyl]-
5-[3-(12,12,12-trichloro-6-dodecenylsulfonyl)phenyl]-4(1H)-
pyridone
3-[2-(3-chloro-5-hexynylsulfonyl)-4-nitrophenyl]-
5-[3-bromo-5-(6-cyanohexyl)phenyl]-1-methoxy-4(lH)-pyridone
3-[4-(6,6-dibromo-3-hexynylsul:Eonyl)phenyl]-5-
phenyl-l-propoxy-4( lH ) -pyridone
3-[3-(2-cyanoethyl)phenyl]-1-ethynyl-5-[1,1,2,2-
tetrafluoro-6-decynylsulfonyl)phenyl]-4(1H)-pyridone
3-(3-benzyl-5-ethynylsulfonylphenyl)-5-[2-~7-
phenylheptyl)phenyl]-l-vinyl-4(lH)-pyridinethione
~ l-cyanomethyl-3-[3-(6-dodecynylsulfonyl)-5-
methylphenyl]-5-[2-methyl-4-(1,1,2,2-tetrafluoroethyl)-
phenyl]-4tlH)-pyridone
1-(2-carboxyethyl)-3-phenyl-5-(3-phenylsulfonyl-
phenyl)-4(lH)-pyridone ~:
3-[3-(4,4-diiodobutyl)phenyl]-5-[4-(4-fluoro- :
phenylsulfonyl)phenyl]-l-trifluoromethyl-4~lH)-pyridone .
3-[2-chloromethyl-3-(6,6-dibromohexyljphenyl]-5- ~ :
[3-(3-iodophenylsulfonyl)phenyl]-1-methyl-4(1H)-pyridone ~:
l-ethyl-3-[3-ethyl-5-(4-methylphenylsulfonyl)-
phenyl]-5-[4-iodo-3-(2-propylbutyl)phenyl]-4(1H)-pyridine-
thione
l-(l-cyanoethyl)-3-[3-(2-propylphenylsulfonyl)-
phenyl]-5-phenyl-4(1H)-pyridinethione
3-[5-butyl-2-(3-methoxyphenylsulfonyl)phenyl]-
~ carboxyethyl)-5-phenyl-4(1H~-pyridinethione
X-4097A -26-
~6~t75~;~6
3-(3-isopropyl-4-trifluoromethylphenyl)~
methyl-5-[3-(2-propoxyphenylsulfonyl)phenyl]-4(11l)-pyridone
3-[2-chloro-4-(4-nitrophenylsulfonyl)phenyl]-1-
ethyl-5-~3-fluoro-5-(4-heptyl)phenyl]-4(1H)-pyridone
3-(3-cyclopropylmethylphenyl)-1-methyl-5-(2-
trifluoromethylphenyl)-4(lH)-pyridone
3,5-bis[3-(2-cyclopentylethyl)phenyl~-1-methoxy~
4(lH)-pyridone
3-(2-cyclopropoxyphenyl)-1-ethyl-5-(2-fluoro- :
phenyl)-4(lH)-pyridinethione
3-(4-cyclohexyloxyphenyl)-1-methyl-5-phenyl-
4(lH)-pyridone, methanesulfonate
3-(4-chlorophenyl)-5-(3-cyclobutylthiophenyl)- :
l-ethoxy-4(lH)-pyridone
3-(2-cyclopentylsulfinylphenyl)-5-(3-hexylphenyl)-
1-propoxy-4(lH)-pyridone, hydrochloride
3-(4-cyclopropylsulfonylphenyl)-5-(2,4-diethyl- :
phenyl)-l-propyl-4(lH)-pyridinethione
3-(3-cyclohexylsulfonylphenyl)-5-(3,5-difluoro-
phenyl)-1-trifluoromethyl-4(1H)-pyridone
l-cyanomethyl-3-(2-cyclopropylmethoxyphenyl)-5-
(3-trlfluoromethylphenyl)-4(lH)-pyridone
l-acetoxy-3 [3-(2-cyclohexylethoxy)phenyl]-5-
phenyl-4(lH)-pyridone, hydrobromide
3-~4-(2-cyclobutylethylthio)phenyl]-1-dimethyl-
amino-5-(3,5-dimethylphenyl)-4(lH)-pyridone
3-(3-cyclopentylmethylsulfinylphenyl) 1-methyl-5-
(3-trifluoromethylphenyl)-4(1H)-pyridone
3-[4-(2-cyclohexylethylsulfonyl~phenyl~ ethyl-
5-(3-propylphenyl)-4(lH)-pyridone
X-4097~ -2~-
~ ~75;69~
3-cyclopropylmethyl-5-(3-fluorophenyl)~
methoxy-4(lH)-pyridone, methanesulfonate
3-(4-chlorophenyl)-3-(2-cyclohexylethyl)-1-
ethoxy-4(lH)-pyridone
3-(3-fluorophenyl)-1-methyl-5-phenylthio-4(lH)-
pyridone
3-(3-chloro-5-methylphenyl)-1-ethoxy-5-phenyl-
sulfinyl-4(lH)-pyridone
l-acetoxy-3-phenylsulfonyl-5-(4-trifluoromethyl-
10 phenyl)-4(lH)-pyridinethione :~
. 3-(2-butylphenyl)-5-~3,5-dichlorophenylthio)-1-
(l-propenyl)-4(lH)-pyridone
3-(2,4-dibromophenyl)-1-dimethylamino-5-(4-
ethylphenylsulfinyl)-4(lH)-pyridone
l-cyanomethyl-3-phenyl-5-(3-propoxyphenyl-
sulfinyl)-4(lH)-pyridinethione
3-methylthio-5-phenyl-1-ll-propynyl)-4(1H)-
pyridone ::
3-(2-chlorophenyl)-1-methyl-5-propylsulfinyl- .
4(lH)-pyridinethione, hydrofluoride
3-ethylsulfonyl-1-isopropyl-5-(3-trifluoro-
methylphenyl)-4(1H)-pyridone .~ . .
l-ethoxy-3-(4-fluorophenyl)-5-trifluoromethyl-
thio-4(1H)-pyridinethione, toluenesulfonate
3-(2-chloroethylsulfinyl)-1-chloromethyl-5-
(3-methylphenyl~-4(lH)-pyridone
3-(2-bromopropylsulfonyl)-1-chlorodifluoro-
methyl-5-phenyl-4~1H)-pyridinethione
1 (1-carboxyethyl~-3-(2,4-dimethylphenyl)-5- :
vinylthio-4(lH)-pyridone
X-4097A -28-
7S6~
3-allylsulfinyl-3-(3,5-diiodophenyl)-1-methyl-
4(lH)-pyridinethione
l-methyl-3-(2-trifluoromethylphenyl)-5-vinyl-
sulfonyl-4(lH)-pyridinethione
3-(3-allylphenyl)-S-(2-chlorovinylthio)-1-
ethoxy-4(1H)-pyridinethione
1-(2-bromoethyl)-3-(2-chloro-3-fluorophenyl)-5-
(1,2-difluoroallylsulfinyl)-4(lH)-pyridone
3-(2-bromo-1-propenylsulfonyl)-1-methyl~5-(3-
methylphenyl)-4(lH)-pyridinethione
l-dimethylamino-3-(4-methoxy-2-butenyl)-5-
phenyl-4(lH)-pyridone
l-ethynyl-3-(2-propoxyvinyl)-5-(3-trifluoro-
methylphenyl)-4(lH)-pyridone.
3-(6-ethoxy-2~hexenyl)-1-methyl-5-phenyl-4(lH)-
pyridinethione, hydrochl.oride
The following are the preferred compounds of
ormula I.
l-methyl-3-phenyl-5-~3-trifluoromethylphenyl)-
4(lH) pyridone
3-(3-fluorophenyl)-1-methyl-5-phenyl-4(lH)--
pyridone
3-(3-chlorophenyl)-1-methyl-5-phenyl-4(1H)-
pyridone
3,5-bis(3-chlorophenyl)-1-methyl-4(1H)-pyridone
3-(3-chlorophenyl)-5-(3-~luorophenyl)-1-methyl-
4(lH)-pyridone
l-methyl-3-(3~methylphenyl)-5-phenyl-4(1H)-
pyridone
'
X 4097A -29- :
' ':
... . - , . .
756~6
3,5-diphenyl-1-methyl-4(lH)-pyridone ;.~ :
l-methyl-3,5-bis~3-trifluoromethylphenyl)-
4(lH)-pyridone
3 (3-bromophenyl)-1-methyl-5-p:henyl-4(lH)--
pyridone
3-(3-methoxyphenyl~-1-methyl-5-phenyl-4(lH)-
pyridone
3-(3-ethoxyphenyl)-1-methyl-5-phenyl-4(lH)-
pyridone :
1-methyl-3-phenyl-5-(3-propoxyphenyl)-4(lH)-
pyridone
3-(3-isopropoxyphenyl)-1-methyl-5-phenyl-4(lH)~
pyridone
l-methyl-3-phenyl-5-13-(1,1,2,2-tetrafluoro-
ethoxy)phenyl]-4(1H)-pyridone
3,5-bis(3-fluorophenyl)-1-methyl-4(lH)-pyridone ..
3-(2-chlorophenyl)-1-methyl-5-(3-trifluoro
methylphenyl)-4(lH)-pyridone
3-(3-chlorophenyl)-1-methyl-5-(3-trifluoromethyl-
phenyl)-4(lH)-pyridone
3-(4-chlorophenyl)-1-methyl-5-(3-trifluoromethyl-
phenyl)-4(1H)-pyridone
3-(2-fluorophenyl)-1-methyl-5-(3-trifluoro-
methylphenyl)-4(lH)-pyridone
3-(3-fluorophenyl)-1-methyl-5-(3-trifluoro-
methylphenyl)-4t1H)-pyridone
3-(4-fluorophenyl)-1-methyl-5-(3-trifluoro-
; methylphenyl-4(1H)-pyridone
3-(3-chlorophenyl)-5-(4-chlorophenyl)-1-methyl- :~
4(1H)-pyridone
X-4097A -30-
''':~ ' ' "
," ~ '
75696
l-ethyl-3-phenyl-5-(3-trifluoromethylphenyl)-
4(lH)-pyridone
l-allyl-3-phenyl-5-(3-trifluoromethylphenyl)-
4(lH)-pyridone
l-methyl-3-(3-trifluoromethylphenyl)-4(lH)-
pyridone
3-chloro-1-methyl-5-(3-trifluoromethylphenyl)-
4(lH)-pyridone
3-bromo-1-methyl-5-~3-trifluoromethylphenyl)-
4(lH)-pyridone
1,3-dimethyl-5-(3-trifluoromethylphenyl)-
4(lH)-pyridone
3-ethyl-1-methyl-5-(3-trifluoromethylphenyl)-
4(lH)-pyridone
3-isopropyl-1-methyl-5-(3-trifluoromethylphenyl)-
4~lH)-pyridone
l-methyl-3-phenyl-5-(3-trifluoromethylphenyl)-
4(1H)-pyridinethione
The process for preparing the compounds of
formula I is an analogous process. Benary and Bitter, Ber.
61, 1058 (1928) taught the synthesis of an intermediate di-
sodium salt of l,5-dih~droxy-2,4-diphenyl-1,4-pentadien-3-
one by the condensation of 1,3-diphenyl-2-propanone with
ethyl formate in the presence of sodium methoxide. The
intermediate pentadienone is neutralized by strong acid
and forms 3,5-diphenyl-4-pyrone. Reaction of the pyrone
with ammonium acetate at an elevated temperature produces
3,5-diphenyl-4.(1H)-pyridone.
X-4097A -31-
:: : .: . .
7~6~
Analogously, 3,5-diphenyl-4(lH)-pyridones can be
prepared by the reaction of an appropriately ring-sub-
stituted 1,3-diphenyl-2-propanone with formamide and for-
mamidine acetate. Reaction at reflux temperature produces
the corresponding 3,5-diphenyl-4(lH3-pyridone, which is
reacted with a halide of the desired l-substitiuent in the
presence of a suitable strong base to form the desired
compound.
The compounds of formula I are prepared by
cyclizing a compound of the formula
~ C-C-C-R~ IV
wherein R , R and m are defined as before,
with an agent selected from the group consisting of
a formylating agent, and
an aminoformylating agent
when one of Ql and Q2 is 2 hydrogen atoms and the other is
=CHNHY wherein Y is hydrogen; hydroxy; C1-C3 alkyl; Cl-C
alkyl substituted with halo, cyano, carboxy or methoxy- ~:
carbonyl; C2-C3 alkenyl; C2-C3 alkynyl; Cl-C3 alkoxy; or .. -~:
dimethylamino; provided that Y comprises no more than 3
carbon atoms; and with a compound of the formula
wherein Y is defined as before or the acid addition salt
thereof, when both Ql and Q2 are independently selected from
the group consisting of :~ :
; . '
X-4097A -32-
~ '
:
756~6
=CHOH
=CHN(R )2
in which the R9 groups independently are Cl-C3 alkyl,
or the R groups combine with the nitrogen atom to which
they are attached to form pyrrolidino, piperidino, mor-
pholino or N-methylpiperazino;
to provide a compound of the formula
R~ V
y
followed by alkylating or esterifying the compound so
obtained wherein Y is hydrogen or hydroxy respectively to
provide the corresponding compound wherein Y is R; and
when the compounds of formula I are desired wherein
X is sulfur, treating the compounds of formula I wherein
X is oxygen with P2S5.
Therefore, the compounds of formula I can be
prepared by cycli~ing a compound of the formula ::
O
~C~ C---R2
R1 X~ = ~/ Q1 Q2 VI
wherein Rl, R2 and m are defined as before~ ~
with a compound of the formula -
N 2 ~ :
wherein Y is defined as before or the acid addition salt
thereof,
X-4097A -33-
7569~
when both Ql and Q2 are independently selected from
the group consisting of
=CHOH
=CHN(R )2
in which R9 is defined as before, to provide a compound
of formula V;
followed by alkylating or esterifying the compound so
obtained wherein Y is hydrogen or hydroxy respectively to
provide the corresponding compound wherein Y is R; and
. 10 when the compounds of formula I are desired wherein
X is sulfur, treating the compounds of formula I wherein
X is oxygen with P2S5.
Thus, it is possible to prepare the compounds
of formula I by cyclizing a compound of the formula
R1 X ~ c__c~ R2 VII
wherein Rl, R2 and m are defined as before,
with an agent selected from the group consisting of
a formylating agent, and
an aminoformylating agent ::
when one of Ql and Q2 is 2 hydrogen atoms and the other
is =CHNHY wherein Y is defined as before, to provide a
compound of formula V;
followed by alky~ating or esterifying the compound so
obtained wherein Y is hydrogen or hydroxy respectively to
provide the corresponding compound wherein Y is R; and `
when the compounds of formula I are desired wherein
X-4097A -34-
. ~
~75~;96
X is sulfur, treating the compounds of formula I wherein X
is oxygen with P2S5.
An embodiment o~ the cyclizing process described
above comprises reacting a compound of ~ormula IV wherein
both of Ql and Q2 are 2 hydrogen atoms with formamide or
1~3,5-triazine to provide an intermediate compound of
formula V wherein Y is hydrogen, followed by alkylation
to provide the corresponding compound of formula I. This
above embodiment also comprises the use o~ formamide with
formamidine acetate.
The preferred embodiment of the synthesis of the
compounds of formula I is adapted from the methods of Benary
and Bitter and of El-Kholy et al., cited above. ~n appro-
priately substituted l-phenyl-2-propanone is formylated at
low temperature with sodium methoxide and ethyl formate in
ether, and the product is treated with an amine salt of the
desired R substituent in aqueous medium. The resulting
intermediate is predominantly a l-(R-amino)-2-phenyl-
l-buten-3-one of formula VII. Some pyridone is also ~ormed
at this step, as reported by El-Kholy et al. The butenone
is reformylated as before, and spontaneously cyclizes to
form the l-substituted-3-phenyl-4(lH)-pyridone of formula I.
It is possible to prepare the intermediate 1-
unsubstituted pyridones by using NH3 in place of YN~2 in
the process, or by using the process of Benary and Bitter.
The pyridone is then alkylated at the l-position with a
halide of R, or with a dialkyl sulfate, according to common
procedures to yield the compounds of formula I.
Another embodiment of alkylation proceeds by
converting the l-unsubstituted pyridone to the ~-halo or
X-~Og7A -35-
,
7~i69~
4-alkoxy derivative by reaction with a halogenating ayent,
or an alkylating agent. Suitable halogenating agents
include such agents as POC13 t POBr3, PC15 and the like.
O-alkylating agents include such reagents as methyl tri
fluoromethanesulfonate, methyl fluorosulfonate and the like,
as well as alkyl halides used in the presence of base. In
the next step, the 4-halo or 4-alkoxy compound is reacted
with a halide of R to form the 1-R-substituted, 4-sub-
stituted pyridinium salt. The salt is then hydrolyzed with
either a mineral acid or an alkali metal hydroxide to
produce the desired product. See, for example, Takahashi
et al., Pharm. Bull. (Japan) 1, 70-74 (1953).
As a chemist would expect, the amines, RNH2, may
be used in the form of salts, preferably hydrohalide salts,
including hydrochlorides, hydrobromides and the like. Such
salts are often more convenient than the free amines.
The formylating agents-used in the proc~ss are
chosen from the common agents used for such reactions. The
preferred agents are esters of formic acid of the formulae
H--C~O-~(Cl-C6 alkyl) or
O ~ :
o_~ .
Similar formylations are discussed in Organic
Syntheses 300-02 ~Collective Vol. III 1955).
The esters are used in the presence of strong
bases, of which alkali metal alkoxides are preferred, such
as sodium methoxide, potassium ethoxide and lithium pro-
X-4097A -36-
- ~9756~6
poxide. Other bases may also be used, including alkali
metal hydrides, alkali metal amides, and inorganic bases
including alkali metal carbonates and hydroxides. Such
strong organic bases as dia~abicyclononane and diazabicyclo-
undecane are also useful.
Reactions with formylating agents are performed in
aprotic solvents such as are regularly used in chemical
synthesis. Ethyl ether is usually the preferred solvent.
Ethers in general, including solvents such as ethyl propyl
ether, ethyl butyl ether, 1,2-dimethoxyethane and tetra-
hydrofuran, aromatic solvents such as benzene and xylene,
and al~anes such as hexane and octane can be used as for-
mylation solvents.
Bec~use of the strong bases used in the formylation
reactions, low temperatures produce the best yields. Reaction
at temperatures in the range of from about -25C. to about
10C~ is preferred. The reaction mixture may be allowed to
warm to room temperature, however, after the reaction has
proceeded part way to completion. Reaction times from about
1 to about 24 hours are adequate for economic yields in the
formylation reactions~
The aminoformylating agents used in these synthe-
ses may be any compounds capable of reacting with an active
methylene group to introduce a =CHN(R912 group, or its acid
addition salt. Such agents are chosen from among the
orthoformamides,
HC[N(R )2]3
the formate ester aminals,
~-4097A
, ... .. -.. . . . . . . ........... - - .
: - . :, - .... . . .. . .
1~7S696
Q3 10
Hl[N(R9) ]
the formamide acetals,
Q3 _ R10
f ( , 2
Q3 R10
the tris(formylamino)methanes, ~-
- Q3
HC(NHCH)3
and the formiminium halides,
9 '.'
HC=N(R )2Halo ~
Halo ;
Q3 in the structures above represents oxygen or sulfur, and
R10 represents Cl-C6 alkyl or phenyl.
Useful references on the aminoformylating agents
include DeWolfe, Carboxylic Acid Derivatives 420-506
(Academic Press 1970), and Ulrich, Chemistry of Imidoyl
Hali~es 87-96 (Plenum Press 1968). Bredereck et al. have
written many papers on such agents and reactions, of which
the following are typical. Ber. 101, 4048 56 (1968); Ber.
104y 2709-26 (1971); Ber. 106, 3732-4Z (1973)i Ber. 97,
3397-406 (1964); Ann. 762, 62-72 (1972); Ber. 97, 3407-17
(1964); Ber. 103, 210-21 (1970~; Angew. Chem. 78, 147
(1966); Ber. 98, 2887-96 (1965~; Ber. 96, 1505-14 (1963);
Ber. 104, 3475-85 (1971); Ber. 101, 41-50 (1968); Ber~ 10Ç,
3725-31 (1973); and Angew. Chem.~ Int'l Ed. 5, 132 (1966).
Other notable papers on the sub~ect include Kreutæberger et -
al., Arch. der Pharm. 301, 881-96 (1968), and 302, 362-75
(1969), and Weingarten et al., J. ~. Chem. 32, 3293-94
(1967).
X-4097A -38-
::
:: ,, ~ . ~ , - . ,
lLlD'7S6,96
~ minoformylations are usually carried out without
solvent, at elevated temperatures from ~bout 50C. to about
200C. Solvents such as dimethylformamide are sometimes
used, however, particularly when it is clesirable to raise
the boiling point of the reaction mixture.
When aminoformylating with formiminium halides,
however, aprotic solvents, such as described above in the
description of solvents for formylation, are used at
temperatures from about 0C. to about 50C., preferably at
room temperature. Halogenated solvents such as chloroform
and methylene chloride can also be used in such amino-
formylations if desired.
The exchange reactions with YNH2 are best per-
formed in protic solvents of which alkanols are preferred
and ethanol is most appropriate. Temperatures from about
-20C. to about 100C. can be used for the exchange re-
actions. Room temperature is satisfactory and is preferred.
The starting materials of formula IV are pre-
pared by reacting a compound of the formula
CH --C--CH ---RZ
R1XD - / 2 Z VIII
m
wherein:
Rl, R2 and m are defined as before,
with an agent selected from the group consisting
of
a formylating agent, and
an aminoformylating agent.
:
X-~097A _39-
; ::
~75696
:
If a formylating agent is used, a ketone inter-
mediate of the formula
Rm,~ _. O
o--C-~C--CH --R2 IX
HOCH
is produced. Reaction with an aminoformylating agent
produces an enaminoketone such as X below.
1 0 , ,
~--~9 î ~ x
(R )2N ~1
Organic chemists will understand that, although
formulae IX and X show the first formylation or amino-
formylation as occurring on a certain side of the ketone, it
may in fact occur on either side of the ketone, depending on
the~activating characteristics of Rl and R2. The course of
the reaction is the same in either case. It will also be
understood that, in many instances, the product of the
formylation or aminoformylation step will actually be a `
mixture containing the two possible monosubstituted com-
pounds and the disubstituted compound.
The monosubstituted product is formylated or ;~
aminoformylated again, and exchanged with an amine of the
formula YNH2. The steps may be performed in either order.
If ~he exchange is performed first, the intermediate product `
is an enaminoketone of the formula
,
X-4097A -40-
:.
.: :
9~ :
Rm ~ i~ ~ XI
C---'C--Ctl - R2
YHNCH
Either formylation or aminoformylation o:E the above enamino-
ketone, which also can be represented by formula VII,
affords the pyridone product, as the intermediate cyclizes
as soon as the second group is introduced on the other :
methylel1e group.
Either of compounds IX or X may be either for-
mylated or aminoformylated to provide intermediates of any
of the formulae below.
R1 0_~ 0
~---C--C~C R2 XII
HOCH HI~OH - ~ .
~o~C--C C~R2 XIII
HOCH HeN (R~
2 . -
~~C^--C~C - R2
o/ 11 11 ~ ~ ~
(R ) 2N~H H~N (R ) 2 :. . .
: :: . '
It will be understood that the compound similar to XIII,
wherein the formyl and aminoformyl groups are reversed, is
equivalent in all respects to compound XIII. Pyridones.,., ::
are formed from any of the above three intermediates, which
can:all be represented by formula VI, by simple contact of
X-4097A 41-
, ,~",
. ~ . .. . . . . .
~7569~
the intermediate with an amine of the formula YNH2.
- The starting 2-propanones of formula VIII may be
prepared by syntheses in the literature. For example, see
Coan et al., J. Am. Chem. Soc. 76, 501 (1954); Sullivan et
al., "Disodium Tetracarbonylferrate", American Laboratory
49-56 (June 1974); Collman et al., "Synthesis o~ Hemi-
fluorinated Ketones using Disodium Tetracarbonylferrate," J.
Am. Chem. Soc. 95, 2689-91 (1973); Collman et al., "Acyl and
Alkyl Tetracarbonylferrate Complexes as Intermediates in the
Synthesis of Aldehydes and Ketones", J. Am. Chem. Soc. 94,
2516-18 (1972).
The compounds of formula X also are prepared
as follows:
(A) ~ -CH2 C -Halo + (R9)2NCH=CH -R2
O
C--C R2 ~,
~ HCN(R )2
It will be understood that reaction (A) can also be per-
formed in the opposite manner, as shown below:
'~
~1~--
====~ ¦¦ 2
It is also possible to form the starting materials of
formula VI wherein both Ql and Q2 are identical by using phos-
~ ,'.
- 42 -
,
;i6~6
gene as the carbonyl halide when the 3- and 5-substituents
of the pyridone product of formula I are identical.
(C) .
R1 ,~
m ~ ~ COCI
\ /o CH=CI~N (R~ 2 __
.,
Rm ~ O " ~ Rm
\
(R9) NCH HCN (R9) t
In general, intermediate compounds in the syn-
thesis are not purified, but are simply used in successive
steps after separation by extraction, neutralization or
removal of excess solvent or reactant as appropriate.
The enamine acylation reactions, A-C, are performed
in the presence of bases such as tertiary amines, alkali
metal carbonates, magnesium oxide and the like, and in
aprotic solvents as described above.
In some instances, as organic chemists will
understand, it is necessary to apply additional synthetic
steps after the pyridone compound has been formed. For
example, it is convenient to form compounds having alkoxy,
alkanoyloxy and like Rl and R5 substituents by first making
the corresponding hydroxy-substituted compound, and then
substituting on the oxygen atom.
The pyridinethiones of formula I are readily
prepared by the treat~ent of the corresponding pyridones
with P2S5 in pyridLne at reflux temperature, according to
known methods.
..~
X-4097A -43- ~
:. : ` . . . : :
;~7~6~6
The l-acetoxy compounds of formula I are made by
first making the corresponding l-hydroxypyridone, using
NH2OH as the amine, and esterifying it with acetic an-
hydride~ The other l-substituents are provided by appro-
priate Y substituents on the amines, YNE12, used to prepare
the pyridones.
The following preparative examples are presented
to assure that those skilled in organic chemistry can obtain
any desired compound of formula I.
The examples below show the various processes by
which compounds of formula I have been made. It will be
understood, however, that all of the various processes can
be used, with appropriate variations, to make any compound
of formula I.
Many exemplary compounds are indicated as made by
the general process of a pre~ious exemplary compound. In
such instances, an ordinarily skilled organic chemist will
readily see the minor changes to the exemplary process which
will be needed to prepare the other exemplary compounds.
Temperatures are given in degrees Centigrade (C.).
Nuclear magnetic resonance spectra (NMR) were determined
on a 60 megaHertz instrument using tetramethylsilane as
an internal reference and are indicated in cycles per
second (CPS~. Melting points (m.p.) were determined by
using a thermal block.
The first example below illustrates the prep-
aration of a compound by the preferred synthetic process
using a compoun~ of formula VII.
X-4097A -44-
~ -
7S6~
Example 1
To a solution of 4 1. of tetrahydrofuran and 284
g. of sodium methoxide was added 556 g. of 1-(3-trifluoro-
methylphenyl)-3-phenyl-2-propanone at 10-15C. over a 20-
minute period. The reaction mixture waic~ stirred for 15
minutes. Then 370 g. of ethyl formate was added over a
period of 30 minutes and the mixture stirred for 1 hour at
10-15C. To the mixture was added an additional ~96 g. of
ethyl formate over a period of 30 minutes. The reaction
mixture was allowed to warm to room temperature and was
stirred overnight. Then, a solution of 336 g. of methyl-
amine hydrochloride in 1 1. of water was added. The
two-phase mixture was stirred at 30C. for 30 minutes. The
mixture was then extracted with methylene chloride, and the
extracts were combined and concentrated under vacuum,
leaving an oily residue which consisted of a mixture con-
taining l-methylamino-2-phenyl-4-(3-trifluoromethylphenyl)-
l-buten-3-one and 1-methylamino-4-phenyl-2-(3-trifluoro-
methylphenyl)-l-buten-3-one.
The residue was reacted by the same procedure of
the previous paragraph. After being dissolved in methylene
chloride, the mixture was washed with water and dried. -
After drying and removal of the solvent, the solid product
was found to weight 430 g., yield 65%. The product was -~
recrystallized from ethyl ether, and the puri~ied product
was identified as l-methyl-3-phenyl-5-(3-trifluoromethyl
phenyl)-4(1H)-pyridone, m.p. 153-155C., by infrared, nuclear
magnetic resonance, and thin-layer chromatography analyses.
The elemental analysis was as follows.
-.:- . '
X-4097A -45-
- .
5~6
Theoretical Found
C6~.30% 69.48
El4.29 4.42
N 4.25 4.27
The process of Example 1 was a]Lso used to produce
all of the following exemplary compounds.
Example 2
l-methyl-3,5-bis(3-trifluoromethylphenyl)-
4(lH)-pyridone, m.p. 152-154C., yield 39
Example 3
3-phenyl-1-(2,2,2-trifluoroethyl)-5-(3-trifluoro-
methylphenyl)-4(lH)-pyridone, NMR, quartet centered at 256
CPS; aromatic protons at 420-468 CPS; yield 46
Example 4
3-(3-bromophenyl)-5-(3-chlorophenyl~-1-methyl-
4(lH)-pyridone, m.p. 192C., yield 23
Example 5
_ _ :
3-(3-chlorophenyl)-5-(4-chlorophenyl) l-methyl-
4(lH)-pyridone, m.p. 170-172C., yield 26%
Example 6
3-(2-fluorophenyl)-1-methyl-5-(3-trifluoromethyl-
phenyll-4(1H)-pyridone, m.p. 152-154C., yield 20%
Example 7
.
3-(2-chlorophenyl)-5-(3-chlorophenyl)-1-methyl-
4(lH~-pyridone, m.p. 160-161C~, yield 15%
Example 8
3-(3-methoxyphenyl)-1-methyl-5-(3-trifluoro-
methylphenyl)-4~1H~-pyridone, m.p. 113-115C., yield 7
X-4097A ~46-
.
11g75~ 6
Example 9
3-(4-chlorophenyl)-1-methyl-S-(3 trifluoro-
methylphenyl)-4(1H~-pyridone, m.p. 153-155C., yield 26%
Example _
l-allyl-3-phenyl-5-(3-trifluoxomethylphenyl)-
4(lH)-pyridone, m.p. 107-109C.~ yield :38%
Example 11
3-(4-isopropylphenyl)-1-methyl-5-phenyl-4(lH)~
pyridone, m.p. 159~C., yield 60%
10 Example 12
3-(2-chlorophenyl)--1-methyl-5-(3-trifluoro- ~i
methylphenyl)-4(lH)-pyridone, m.p. 191-193C., yield 14
Example 13
3-(3-fluorophenyl)-1-methyl-5-(3-trifluoromethyl-
phenyl)-4(lH)-pyridone, m.p. 94-96C., yield 13%
Example 14
3-(4-fluorophenyl)-1-methyl-5-(3-trifluoromethyl-
phenyl)-4(lH)-pyridone, m.p. 133-134C., yield 29%
Example 15
3-(4-methoxyphenyl)-1-methyl-5-(3-trifluoromethyl-
phenyl)-4(lH)-pyridone, m.p. 162-165C,, yield 33%
The next example illustrates a synthesis where
the enaminoketone of formula X is reacted first with an
amine to form a compound of formula VII, and then with an
aminoformylating agent to form the desired pyridone of
formula I.
X-4097A -47-
~(117~69~
Example 16
An enaminoketone, ~-pheny~ diethylaMino-4-
(3-methylthiophenyl)-1-buten-3-one, was made according to
the procedure of the first step of Example 73, starting with
17.5 g. of N,N-diethylstyrylamine and 15 g. of (3-methyl-
thiopheny])acetyl chloride. The enaminoketone was dissolved
in 300 ml. of ethanol, mixed with 20 g. of methylamine
hydrochloride and stirred for about 24 hours. The solvent
was then evaporated, the residue was extracted with ethyl
ether, and the solution was washed with water. The organic
layer was dried over anhydrous sodium sulfate, and the dried
solution was evaporated to dryness to yield l-methylamino-
4-(3-methylthiophenyl)-2-phenyl-1-buten-3-one.
The residue was mixed with 50 ml. of dimethyl-
formamide dimethyl acetal and heated at reflux temperature
for 20 hours. The reaction mixture was then poured into
water, and the mixture was extracted first with ether and
then with me-thylene chloride. Both extracts were washed
with water, dried and evaporated to dryness. The product
was 9 g. of 1-methyl-3-(3-methylthiophenyl)-5-phenyl-
4(lH)-pyridone, which was identified by NMR, which showed
peaks at 144 and 227 CPS, with aromatic protons at 420-440
and 442-458 CPS.
By a similar process, the following-compounds were
also produced. Examples 17 and 18 were produced by
oxidation of the compound of Example 16 with _-chloro-
perbenzoic acid.
Examele 17
._
l-methyl-3-(3-methylsulfinylphenyl1-5-phenyl-
4(lH)-pyridone, m.p. 161-164C., yield 57%
X-4097A -48-
~175696
Example 18
l-methyl-3-(3-methylsulfonylphenyl)-5-phenyl-
4(lH)-pyridone, m.p. 176-181C., yield 31
Example 19
l-methyl-3-phenyl-5-~4-trifluoromethylphenyl)-
4(1H)-pyridone, m.p. 164-166C., yield 16%
The following example illustra~es a variation of
the process beginning with a carbonyl halide, wherein the
enaminoketone of formula X is first exchanged with an amine
to form a compound of formula VII, and the pyridone of
formula I is then formed by formylation oE the intermediate.
Example 20
An enaminoketone was prepared, namely, 4-(3-
benzyloxyphenyl)-l-diethylamino-2~-phenyl-1-buten-3-one,
following the first step of the procedure of Example 73,
from 14.4 g. of (3-benzyloxyphenyl)acetyl chloride and 9.6
g. of N,N-diethylstyrylamine. A 13 g. portion of the
enaminoketone was dissolved in 100 ml`. of methanol and 26 g.
of methylamine hydrochloride was added. The reaction
mixture was heated at reflux temperature overnight. The
solvent was removed under vacuum, 100 ml. of water was
added, and the mixture was then extracted with methylene
chloride. The extract was washed with dilute hydrochloric
acid and then with water, and the organic layer was sepa-
rated! dxied, filtered and evaporatedl to dryness. The
resulting intermediate, 4-(3-benzyloxyphenyl)-1-methyl-
amino-2-phenyl-1-buten-3-one, was dissolved in 125 ml. of -
ethyl ether.
.
X-40g7A -49-
.. .
.. .... .... ..... . .. ..
: . . . :.
~7S6~
The solution was cooled to 5C., and 12 g. of
sodium methoxide was added. While the xeaction mixture was
held at about 5C., 50 ml. of ethyl formate was added
slowly. The mixture was then stirred as it was allowed tv
warm slowly to room temperature. The reaction mixture was
then evaporated to dryness, the residue was extracted with
chloroform, and the extract was washed with water and
dried. The product was purified by chromatography over
silica gel with a 50:50 mixture of ethyl acetate:hexane.
The product-containing fractions were collected, combined,
and e~apor$ted to dryness. The product was recrystallized
from ethyl acetate to produce 1.5 g. of 3-(3-benzyloxyphenyl)-
l-methyl-5-phenyl-4(lH)-pyridone, m.p. 158-160C.
The following exemplary compounds were also pro-
duced according to the process of Example 20 above,
Example 21
l-methyl-3-phenyl-5-(2-thienyl~--4(lH)-pyridone,
m.p. 147-148~C., yield 6%
Example 22
3-(3-isobutylphenyl) :L-methyl-5-phenyl-4(lH)-
pyridone, NMR doublets at 54 and 147 CPS; a septet at 113
CPS; aromatic protons at 420-460 CPS.
Example 23
l-methyl-3-(3-nitrophenylj-5-phenyl-4(1H)-
pyridone, m.p. 135-136.5C., yield 33~
The following example demonstrates the preparation
of a pyridone by the formamidine acetate process, followed
by alkylation at the l-position.
Example 24
Ten g. of 1-(2,4-dichlorophenyl)-3-phenyl-2-
X-4097A -sa-
7~ 9~
propanone was heated a-t reflux with 10 g. of formamldine
acetate in 75 ml. of formamide for 3 hours. The mixture was
then poured on-to ice and water was addedO After the ice had
melted, the mixture was filtered and the separated solids
were washed with ethyl ether. The solids were then dis-
solved in ethanol, decolorized with charcoal and recrystal-
lized to produce 1.3 g. of 3-(2,4-dichlorophenyl)-5-
phenyl-4(lH)-pyridone, which was identified by infrared and
nuclear magnetic resonance analyses.
The above pyridone was added to a solution of 0.5
g. of 50 percent sodium hydride in 60 ml. of DMSO and warmed
until the pyridone dissolved. Excess methyl iodide was then
added and the mixture was stirred for one-half hour. The
mixture was then poured into water and filtered. The solids
were extracted with methylene chloride, which was then dried
with magnesium sulfate and evaporated to dryness. The
residue was recrystallized from benzene-hexane to give 1.1
g. of 3-(2,4 dichlorophenyl)-1-methyl-5-phenyl-4tlH)-
pyridone, m~p, 202-204C., which was identified by nuclear
magnetic resonance and infrared analyses. The results
of elemental microanalysis were as follows.
Theory Found
C 66.68% 66.84%
H 3.33 4.05
N ~.09 4.01
The following exemplary compounds were made by the
general process of Example 24. In some instances, the
1-unsubstituted pyridone intermediate was made by the prior
art procedure o~ Benary and Bitter, cited aboveO
'
X-4097A -51- ~
:
. .
: L~375696
Example 25
3,5-diphenyl-1-ethyl-4(1H)-pyridone, m.p. 171C.,
yield 75~
~xample 26
l-allyl-3,5-diphenyl-4(lH)-pyridone, m.p. 174C.,
yield 79~
Example 27
3,5-diphenyl-1-isopropyl-4~1H)-pyridone, m.p.
152C., yield 15
Example 28
l-cyanomethyl-3,5-diphenyl-4(lH)-pyridone, m.p.
221-224C., yield 55~
The next example illustrates the variation of the
formylation process wherein the starting ketone of formula
VIII is diformylated to form a compound of formula VI, and
the pyridone is formed by exchange with an amine.
Example 29
....
A 100 g. portion of 1,3-diphenyl-2-propanone was
dissolved in 35 g. of ethyl formate and added to 25 g. of
sodium methoxide in 500 ml. of ethyl ether at 0-5C. over a
30-minute period. The reaction mixture was then allowed to
warm to room temperature and was stirred overnight. The
mixture was then filtered to yield 460 g. of the disodium
salt of 1,5-dihydroxy-2,4-diphenyl-1,4-pentadien-3-one, which
was used in the next step without purification.
A 20 g. portion of the crude salt above was added
to a solution of 20 g. of propylamine and 5 ml. of con-
centrated hydrochloric acid in 75 ml. of watsr. The mixture
was stirred for one-half hour at room temperature. The
X-4097A -52-
''
756g6
reaction mixture was tllen e~tracted witll ethyl ether, an~
the aqueous layer was evaporated to dryness. The residue
was extracted with chloroform, the co~bined organic extracts
were evaporated to dryness, and the residue was recrystal-
lized from benzene-hexane to produce 3.05 g. of 3,5-di-
phenyl-l-propyl-4(lH)-pyridone, m.p. 172-174C.
The following typical compounds were also made by
the general process of Example 29.
Example _
3,5-diphenyl-1-methoxy-4(lH)-pyridone, m.p.
165C., yield 95%
Example 31
3-(3-fluorophenyl)-1-methyl-5-phenyl-4(1H)-
pyridone, m.p. 133.5C., yield 69
Example 32
~ . _
3-(4-bromophenyl)-1-me-thyl-5-phenyl-4(lH)-
pyridone, m.p. 172C., yield 63%
Example 33
3-(4-methoxyphenyl)-1-methyl-5-phenyl-4(lH)-
pyridone, m.p. 165C., yield 32%
Example 34
3-(3-chlorophenyl)-1-methyl-5-phenyl-4(1H)-
pyridone, m.p. 17205C., yield 27
Example 35
_
3-~4-chlorophenyl)-1-methyl-5-phenyl-4(lH)-
pyridone, m.p. 141.5C., yield 76%
Exam~ 36
l-methyl-3-(1-naphthyl)-5-phenyl-4(lH)-pyxidone,
NMR peaks at 204 and 483 CPS; aromatic protons at 430 470
CPS; yield 12~
X~4~9~ -53-
~ ~7S6~6
Example _
3,5-bis(3-chlorophenyl)-1-methyl-4(lH)-pyridone, m.p. 164-
167C., yield 59%
Example 38
l-methyl-3-(3-methylphenyl)-5-phenyl-4(1H)-pyridone (complex
containing 1/2 mole of benzene), m.p. 79.5C., yield 25%
Example 39
l-methyl-3-(4-methylphenyl)-5-phenyl-4(1H)-pyridone, m.p.
144.5C., yield 28%
Example _
l-methyl-3-(2-methylphenyl)-5-phenyl-4(lH)-pyridone, NMR
peaks at 133 and 201 CPS; aromatic protons at 420-440 and
442-460 CPS; yield 16%
Example 41
3-(4-fluorophenyl)-1-methyl-5-phenyl-4(lH)-pyridone, m.p.
166C., yield 60%
Example 42
. _ . _ .
l-methyl-3-phenyl-5-(3-trifluoromethylphenyl)-4(1H)-
pyridone, mOp. 152-156C., yield 52%
Example 43
_ _ _ _
3-(3-methoxyphenyl)-1-methyl-5-phenyl-4(1H)-pyridone, NMR
peaks at 200 and 220 CPS; aromatic protons at 420-440 and
442-460 CPS; yield 33%
Example 44
3-(3,4-dichlorophenyl)-1-methyl-5-phenyl-4(lH)-pyridone,
m.p. 166.5C., yield 54
Example 45
3-(2,5-dichlorophenyl)-1-methyl-5-phenyl-4(1H~-pyridoné,
m.p. 155.5C., yield 22%
X-4097A -54_
~C~75~
~xample 46
_
3-(2-chlorophenyl)-1-methyl-5-phenyl-4(1H)-pyridone, m.p.
145C., yield 29%
Example 47
3,5-bis(3-fluorophenyl)-1-methyl-4(lH)-pyridone, m.p.
149-151C., yield 60%
Example 48
3-(3-chlorophenyl)-5-(3-fluorophenyl)-1-methyl-4(lH)-
pyridone, m.p. 145-146C., yield 64%
_xample 49
3-(3,5-dichlorophenyl)-1-methyl-5-phenyl-4(lH)-pyridone,
m.p. 131-135C., yield 28%
Example 50
3,5-bis(3-bromophenyl)-1-methyl-4(1H)-pyridone, m.p.
216.5C., yield 43%
Example 51
3-(3-bromophenyl)-1-methyl-5-phenyl-4(lH)-pyridone, m.p.
172C., yield 38%
Example 52
3-(2-fluorophenyl)-1-methyl-5-phenyl-4(1H)-pyridone, m.p.
165C., yield 19
Example 53
3-(3-bromophenyl)-1-methyl-5-(3-trifluoromethyl-
phenyl)-4(lH)-pyridone, m.p. 151-153C., yield 37%
Example 54
. .
l-(l-carboxyethyl)-3-phenyl-5-(3-trifluoromethyl-
phenyl)-4(lH)-pyridone, m.p. 236-237C., yield 13
Example 55
. . ._ _
l-dimethylamino-3,5-diphenyl-4(lH)-pyridone, m.p.
143C., yield 94~
X-4097A -55-
~ 13756~6
Example 56
l-methyl-3-(2-naphthyl)-5-phenyl-4(1H)-pyridone,
m.p. 101-105C., yield 45%
Example 57
l-ethyl-3-phenyl 5-(3-trifluoromethylphenyl)-
4(lH)-pyridone, m.p. 98-100C., yield 66
Example 58
3-phenyl-1-propyl-5-(3-trifluoromethylphenyl)-
4(lH)-pyridone, NMR, triplet peaks at 60 and 230 CPS, and a
sextuplet at 114 CPS; yield 42
Exam~le 59
l-methoxy-3-phenyl-5-(3-trifluoromethylphenyl)-
4(lH)-pyridone, NMR peak at 248 CPS
Example 60
3-(3-chlorophenyl)-1-methyl-5-(3-trifluoromethyl-
phenyl)-4~lH)-pyridone, m.p. 133-135C., yield 28
Example 61
~ 3-(4-biphenylyl)-1-methyl-5-phenyl-4(lH~-pyridone,
m.p. 186-190C., yield 1%
Example 62
.. . ~
3-(3-biphenylyl)-1-methyl-5-phenyl-4(lH)-pyridone,
m.p. 186-190C., yield 2
The following example illustrates the synthesis
of pyridones by the di(aminoformylation) of ketones, followed
by exchange with amines.
Example 63
A mixture of 26.8 g. of phenylacetone and 71.4 g.
of dimethylformamide dimethyl acetal in 100 ml. of anhydrous
dimethylformamide was refluxed for 5 days. The reaction
mixture was then evaporated to dryness under vacuum.
X-4097A -56-
.
.
~75696
Analysis of the remaining dark red oil showed that itconsisted of about 75% of the desired 1,5-bis(dimethylamino)-
2-phenyl-1,4-pentadien-3-one, and about 25~ of the cor-
responding monoaminoformylated compound. The yield was 30
g., and -the intermediate was used without purification.
The mixture prepared above was dissolved in 100
ml. of denatured ethanol, and 30 g. of methylamine hydro-
chloride was added. The mixture was refluxed overnight, and
the solvent was removed under vacuum. The residue was taken
up in methylene chloride, and the solution was washed with water
and saturated aqueous sodium chloride solutionO The washed
organic layer was dried over magnesium sulfate, and the
solvent was removed under vacuum. The remaining oil was
shaken with ethyl ether. The solid product which pre-
cipitated from the ether was washed with further ether and
air dried. The product was recrystallized from isopropyl
ether-methylene chloride to produce 10 g. of purified 1-
methyl 3-phenyl-4(lH)-pyridone, m.p. 123-125C.
Example 64
A 3 g. portion of the product of Example 63 was
dissolved in 10~ ml. of water, and aqueous bromine was added
dropwise until no more precipitate formed on further
addition. The precipitate was removed by filtration, washed
with water and air dried. The product was recrystalli7ed
from ethanol to yield 3 g. oE 3-bromo-1-methyl 5-phenyl-
4(1H~-pyridone, m.p. 195~ 197Co
The procedure of Example 63, and of Example 64
where appropriate, was used to prepare the following com--
pounds.
X-4097A - _57_
.: ,
~L~75696
Example 65
3-bromo-1-methyl-5-(3-trifluor~methylphenyl)-
4(lH)-pyridone, m.p. 167-169C., yield 76
Example _
l-methyl-3-(3-trifluoromethylphenyl)~4(lH)-
pyridone, m.p. 122-123C., yield 16~
~ _
3-chloro-1-methyl-5-(3-trifluoromethylphenyl)-
4(lH~-pyridone, m.p. 170-172C., yield 67%
Exam~le 68
3-(3-carboxyphenyl)-1-methyl-5-phenyl-4(lH3-
pyridone, hydrochloride, m.p. 266-268C,, yield 10
EXample 69
3-(3-cyanophenyl)-1-methyl-5-phenyl-4(lH)-
pyridone, m.p. 164-166C~, yield 33%
Example 70
.. ..
3-(3-ethoxycarbonylphenyl)-1-methyl-5-phenyl-
4(1H)-pyridone! m.p. 167-168C., yield 11%
Example 71
3,5-bis(3-cyanophenyl)-1-methyl-4~lH)-pyridone,
m.p, 322-327C., yield 22
Example 72
l-methyl-3-phenyl-$-(3-thienyl)~4(1H)-pyridone,
NMR peaks at 204 and 495 CPS; aromatic protons at 430-460
CPS: yield 34%
The following example demonstrates the synthesis
where the corresponding enaminoketone of formula X is
aminoformylated to form a compound of formula VI, and the
pyridone is formed by exchange with an amine.
X-4097A -58-
.
- - . .
~, . - .
.. : .: .: . : :
~97S6~6
Example 73
A mixture of 1.92 g. of dime-thylaminoacrylonitrile
and 1.6 g. of pyridine was dissolved in ~5 ml. of ethyl
ether at 0C. A 3.08 g. portion of phenylacetyl chloride in
25 ml. of ethyl ether was added dropwise, and the mixture
was stirred for 2 hours at O~C. after completion of the
addition. The mixture was then evaporated to dryness under
vacuum. The residue was taken up in methylene chloride,
washed with water, dried and evaporated to dryness again.
Upon standing, the mixture began to crystallize, and the
solids were separated by filtration and recrystallized from
isopropanol to yield 400 mg. of 2-cyano-1-dimethylamino-
4-phenyl-1-buten-3-one.
` A 300 mg. portion of the above enaminoketone and
10 ml. of dimethylformamide dimethyl acetal was heated at
reflux temperature for 12 hours. The mixture was th~n
evaporated under vacuum. To the residue was added 25 ml. of
denatured ethanol and 1 g. of methylamine hydrochloride.
The ethanol solution was heated at reflux Eor 12 hours more
and evaporated to dryness, and the residue was taken up in
methylene chloride. After washing with water and drying,
the organic solution was evaporated to dryness, and the
residue was triturated in ethyl ether and filtered. The
solids were recrystallized ~rom isopropyl ether acetone to
yield 260 mg. of 3-cyano-1-methyl-5-phenyl-4(lH)-pyridone,
m.p. 209-210.
The following exemplary compounds were prepared
according to the general process of Example 73 above.
X-4097A -59-
~a~7s696
Example 74
1,3-dimethyl-5-(3-trifluoromethylphenyl)-4(lH)-
pyridone, m.p. 130-131C., yield 12%
Example 75
1,3-dimethyl-5-phenyl-4(lH)-pyridone, m.p. 111-
113C., yield 8%
Example 76
3-(3-chlorophenyl)-1,5-dimethyl-4(1H)-pyridone,
m.p. 143-143.5C., yield 6%
Example 77
3-ethyl-1-methyl-5-(3-trifluoromethylphenyl)-
4(lH)-pyridone, m.p. 95.5-96.5C.I yield 7%
Example 78
3-cyclohexyl-1-methyl-5-(3-trifluorome~hylphenyl)-
4(lH)-pyridone, m.p. 174-175C., yield 40%
Example _
3-isopropyl-1-methyl-5-(3-trifluoromethylphenyl)-
4(lH)-pyridone, m.p. 98.5-99.5C., yield 10%
Example _
3-hexyl-1-methyl-S (3-trifluoromethylphenyl)-
4(lH)-pyridone, m.p. 89.5-90.5C., yield 7%
Example 81
3-benzyl-1-methyl-5-(3-trifluoromethylphenyl)--
4(lH)~pyridone, m.p. 98-100C., yield 18%
Example 82
.
3-butyl-1-methyl-5-~3-trifluoromethylphenyl)
4~lH)-pyridone, m.p. 82.5-84C., yield 9%
Example 83 ;
3-(3-cyclohexenyl)-l~methyl-5-(3-trifluoromethyl
phenyl)-4(lH)-pyridone, m.p. 194-195C., yield 43
X-4097A -60-
.. . . . . .. . .
~ 75g;;96
Example 84
l-methyl-3-propyl-5-(3-trifluoromethylphenyl)-
4(1H~-pyridone, m.p. 45-47C~, yield 3%
Example 85
l-methyl-3-(4-nitrophenyl)-5-phenyl-4(lH)-
pyridone, m.p. 212-214C., yield 48
Example 86
3,5-bis(3,4-dimethoxyphenyl)-1-methyl-4(1H)-
pyridone, m.p. 182-184C., yield 1
Exam~le 87
3-ethoxycarbonyl-1-methyl-5-phenyl-4(1H)-
pyridone, m.p. 107-108C., yield 68%
Exam~e 88
3-(2-furyl)-1-methyl-5-phenyl-4(lH)-pyridone,
m.p. 191-192C., yield 69
Example _
3-cyano-1-methyl-5-(3-trifluoromethylphenyl)-
4(lH)-pyridone, m.p. 228-229C., yield 40%
Example 90
3-(3,4-dimethoxyphenyl~-1-methyl-5-phenyl~4(1~)-
pyridone, m.p. 154- 157C., yield 4%
Exam~le 91
::
3-~3,4-dibromocyclohexyl)-1-methyl-5-(3-tri-
fluoromethylphenyl)-4(lH~-pyridone, hydrobromide, m.p.
196-198C., yield 26%, made by bromination of the cor-
responding 3-(3-cyclohexenyl) compound
Example 92
____ _ :
3-(3-isopropenylphenyl~ methyl-5-phenyl-4(1H)-
pyridone, NMR peaks at 125, 214, 302 and 327 CPS; aromatic
protons at 420-470 CPS; yield 4%
X-4097A -61-
6g6
Example 93
3-(3-ethylphenyl)-1-methyl-5-phenyl-4(1H)-
pyridone, m.p. 135-137C., yield 5
Exam~
3-(3-hexylphenyl)-l~methyl-5-phenyl-4(lH)-
pyridone, m.p. 93-95C., yield 6
Example 95
3-(4-ethylphenyl)-1-methyl-5-phenyl-4(1H)-
pyridone, m.p. 143-145C., yield 6%
Example _
3-(3-cyclohexylmethylphenyl)-1-methyl-5-phenyl-
4(lH)-pyridone, m.p. 147-148C., yield 9%
Example 97
l-methyl-3-phenyl-5-benzylthio-4(lH)-pyridone,
m.p. 155-157C., yield 36
Example 98
l-methyl-3-phenyl-5-phenylthio-4(lH)-pyridone, ;
m.p. 164-165C., yield 18
Example 99
1-methyl-3-phenoxy-5-phenyl-4(lH)-pyridone, m.p.
176-177C., yield 19%
~xam~le 100
l-methyl-3-phenyl-5-phenylsulfonyl-4(lH)-pyridone,
m.p. 218-220C., yield 50%, made by oxidation of the cor-
responding phenylthio compound with m-chloroperbenzoic acid
The next example illustrates a process wherein
the enaminoketone of formula X is first formylated to form
a compound of formula VI and then exchanged with the amine
to form the pyridone.
X~4097A -62~
1~7~i6~6
Example 101
An enaminoketone was formed from 3.5 g. of N,N-
diethylstyrylamine and 2.16 g. of methoxyacetyl chloride in
the presence of 2 g. of triethylamine. The yield was
about 5 g~ of the desired enaminoketone, l-diethylamino-
4-methoxy-2-phenyl-1-buten-3-one.
The above enaminoketone was mixed with 3.2 g. of
sodium methoxide in 50 ml. of dry tetrahydrofuran at 0C.,
and 4.4 g. of ethyl formate was added dropwise. After the
mixture had stirred for three hours, 25 ml. of 40% aqueous
methylamine was added, followed by 5 g. of methylamine
hydrochloride. The mixture was stirred overnight at xoom
temperature, and the solvents were removed under vacuum.
The residue was taken up in methylene chloride, washed with
water and saturated sodium chloride solution and dried. The
solvent was then removed under vacuum, and the residue was
triturated with ethyl ether. The solids were recrystallized
from isopropyl ether-methylene chloride to produce 1 g. of
3-methoxy-1-methyl-5-phenyl-4(lH)-pyridone, m.p. 153-155C.
The following examples illustrate the preparation
of 3-hydroxyphenyl-substituted compounds, from which other
substituted compounds are prepared in the next examples
following.
Example 102
A 1 g. portion of the product of Example 20 was
dissolved in 25~ ml. of acetic acid, and 1 g. of 5~ pal-
ladium on carbon was addedO The mixture was hydrogenated
for about 45 minutes, fil~ered, and the filtrate was evapo-
rated to dryness. The product was recrystallized from ethyl
X-~097~ -63-
,. ~ .
~L~756~;
acetate-hexane to produce 0.45 g. of 3-(3-hydroxyphenyl)-
l-methyl-5-phenyl-4(1H)-pyridone, m.p. 223-225C.
The same compound was also made by a cleavage with
pyridine hydrochloride as follows.
A 2 g. portion of 3-(3-methoxyphenyl)-1-methyl-
5-phenyl-4(lH)-pyridone was mixed with 15 g. of pyridine
hydrochloride and the mixture was heated at reflux temp-
erature for about 1 hour. The mixture was then poured into
a large amount of water, and the precipitated solids were
separated by filtration. The solids were then recrystal-
lized from ethanol-ethyl ether to yield 1.1 g. of 3-(3-
hydroxyphenyl)-l-methyl-5-phenyl-4(lH)-pyridone. An ad-
ditional 0.65 g. was recovered by concentration of the
filtrate above. The product was identical to that of the
above paragraph.
The following compound was made by a process
similar to Example 102.
Example 103
3-cyclohexyl-5-(3-hydroxyphenyl)-1-methyl-4(lH)-
pyridone, m.p. 155-165C., yield 13
Example 104
A 3.2 g. portion of the product of Example 102 was
added to a suspension of 0.86 g. of sodium hydride in 50 ml.
of dimethylsulfoxide. The mixture was stirred at room
temperature, and 3.5 g~ of ethyl iodide was added. The
mixture was stirred for two and one-half hours more, poured
into water, and the aqueous mixture was extracted with ethyl
acetate. The extract was washed with dilute hydrochloric
acid and then with water, and dried. The dried extract was
then filtered and concentrated to dryness u~der vacuum. The
X-4097A -64-
.. . .
75~96
product was 2.2 g. of 3-(3-ethoxyphenyl)-1-methyl-5-
phenyl-4(1H)-pyridone, m.p. 133-135C.
The exemplary compounds below were prepared
according to methods similar to that of Example 104.
Example 105
3-(3-allyloxyphenyl)-1-methyl-5-phenyl-4(lH)-
pyridone, NMR peaks at 211 and 270 CPS; broad peaks at
296-328, 341-378 and 399-458 CPS; yield 10%
Example 106
3-[3-(1-fluoro-2-iodovinyloxy~phenyl]-1-methyl-
5-phenyl-4(lH)-pyridone, NMR peaks at 218 CPS; a broad peak
at 270-316 CPS; aromatic protons at 416-464 CPS; yield 67
Example 107
3-(3-isopropoxyphenyl)-1-methyl-5-phenyl-4(lH)-
pyridone, NMR peaks at 81, 209 and 276 CPS; aromatic protons
at 401-468 CPS; yield 18%
Example 108
3-(3-cyanomethoxyphenyl)-1-methyl-5-phenyl-4(1H)
pyridone, NMR peaks at 207 and 275 CPS; aromatic protons at
396-456 CPS; yield 6%
Example 109
3-(3-dodecyloxyphenyl)-1-methyl-5-phenyl-4~1H)-
pyridone, NMR peaks at 52, 207 and 234 CPS; a broad peak at
60-122 CPS; aromatic protons at 396-461 CPS; yield 26%
Example l
l-methyl-3-[3-(4-nitrophenoxy)phenyl~-5-phenyl-
4(1H)-pyridone, NMR peaks at 222 and 488.5 CPS; aromatic
protons at 414-463 CPS; yield 14%
X-4097A -65-
i~756~a6
Example 111
.
l-methyl-3-(3-methylsulfonyloxyphenyl)-5-phenyl-
4(lH)-pyridone, NMR peaks at 185 and 213 CPS aroma~ic
protons at 422-472 CPS; yield 20%
Example 112
l-methyl-3-phenyl-5-[3-(1,1,2,2-tetrafluoro-
ethoxy)phenyl]-4(1H)-pyridone, m.p. 119-121C., yield 84%, made
by using tetrafluoroethylene, in the presence of potassium
hydroxide
Example 113
3-(3-acetoxyphenyl)-1-methyl-5-phenyl-4(lH)~
pyridone, NMR peaks at 134 and 210 CPS; aromatic protons at
415-466 CPS; yield 28%, made by using acetic anhydride
Example 114
3-(3-hexyloxyphenyl)-1-methyl-5-phenyl-4(lH)-
pyridone, NMR peaks at 53, 214 and 239 CPS; a broad peak at
60-120 CPS; aromatic protons at 402-465 CPS; yield 55~ :~
Example 115
3-(3-decyloxyphenyl)-1-methyl-5-phenyl-4(lH)-
pyridone, NMR peaks at 53, 211 and 239 CPS; a broad peak at
62-123 CPS; aromatic protons at 404-467 CPS; yield 24%
Example 116
1-methyl-3-phenyl-5-(3-propoxyphenyl)-4(lH)- :
pyridone, NMR peaks at 54, 101.5, 208 and 232 CPS; aromatic
protons at 400-463 CPS; yield 31
Example 117
l-methyl-3-phenyl-5-(3-propargyloxyphenyl)-
4(lH)-pyridone, NMR peaks at 150 and 215 CPS; a broad peak
at 280-285 CPS; aromatic pr~tons at 430-470 CPS; yield 6
X 4097A -66-
. ,. . ,. : . . .
1~7Si696
Exam~le 118
3-(3-cyclohexylmethoxyphenyl)-1-methyl-5-phenyl-
4(lH)-pyridone, NMR peaks at 214 and 226 CPS; a broad peak
at 35-124 CPS; aromatic protons at 402-466 CPS; yield 16%
Example 119
l-methyl-3-(3-octyloxyphenyl)-5-phenyl-4(1H)-
pyridone, NMR peaks at 52, 218 and 239 CPS; a broad peak at
58-122 CPS; aromatic protons at 403-467 CPS; yield 19
Example 120
-
1-methyl-3-(3-phenoxyphenyl)-5-phenyl-4(lH)-
pyridone, NMR peak at 214 CPS; aromatic protons at 410-470
CPS; yield 34%
The following example demonstrates a synthesis
starting with a ketone, wherein the starting compound is
first formylated to form a compound of formula IX, then
aminoformylated to form a compound of formula VI, and finally
exchanged with an amine to form the pyridone~
Example 121
A 12 g. portion of sodium methoxide was suspended
20 in 150 ml. of ethyl ether~ The suspension was chilled in an ~ -
ice bath, and 28g. of 1-phenyl--3-(3-trifluoromethylphenyl)~-2-
propanone was added. A 14 g. portion of ethyl formate was
then added dropwise to the stirred mixture. While the
reaction mixture was stirred constantly, it was allowed to
warm slowly to room temperature overnight. In the morning,
the mixture was Pxtracted with water, and the water layer
was made acid with dilute hydrochloric acid and was ex-
tracted with methylene chloride. The organic layer was then
extracted with dilute aqueous sodium hydroxide, and the
water layer was made acid with dilute hydrochloric acid and
X-4097A -67-
... - . . . . . . . . , . . ., .
. : , . . , , . : ..
~L~7S6~6
was then extracted with methylene chloride. The organic
extract was dried, and was evaporated to dryness under
vacuum to produce an oil which was predominantly 1-hydroxy-
2-phenyl-4-(3-trifluoromethylphenyl)-1-buterl-3-one
An 11 g~ portion of the above intermediate product
was heated on the steam bath with 20 ml. of dimethylform-
amide dimethyl acetal for 16 hours. The reaction mixture
was then evaporated to dryness under vacuum, and the residue
was taken up in 150 ml. of ethanol. Ten g. of methylamine
hydrochloride and 20 ml. of 40% aquaous methylamine was
added, and the mixture was stirred at reflux temperature
overnight. The reaction mixture was then evaporated under
vacuum to produce an oil. The oil was taken up in chloro-
forml and the solution was washed with water and dried over
sodium sulfate. The solvent was then removed under vacu~m,
and the residue was triturated with ethyl ether. The ether
was filtered to produce l-methyl-3-phenyl-5-(3-trifluoro-
methylphenyl)-4~lH)-pyridone, m.p. 153-155C.
The next examples below shows the synthesis of a
pyridone, starting from a ketone, by successive amino-
formylation to form a compound of formula X, formylation
to form a compound of formula VI, and exchange with an
amine.
Example 122
A 28 g~ portion of 1-(3-trifluoromethylphenyl)-
3-phenyl-2-propanone was mixed with 12 g. of dimethylfor-
mamide dimethyl acetal, and heated on the steam bath under a
trap which removed ethanol as it was formed. Heating was
continued overnight, after which the reaction mixture was
X-4097A -68-
.. . . . . .
~L~756~;
evaporated to produce an oil which was primarily a mixture
of l-dimethylamino-4-phenyl-2-(3-trifluoromethylphenyl)
l~buten-3-one and 1-dimethylamino-2-phenyl-4 (3-trifluoro-
methylphenyl)-l-~uten-3-one.
A 5 g. portion of the above intermediate was
formylated with ethyl formate in the presence of sodium
methoxide according to the process of Example 121. The
product of the formylation was dissolved in ethanol, and
treated with 5 g. of methylamine hydrochloride and 20 ml. of
40% aqueous methylamine. The mixture was stirred overnight
at reflux temperature, after which the solvent was removed
under vacuum, 100 ml. of water was added to the ~residue and
the mixture was extracted with ethyl ether. The ether
solution was dried over sodium sulfate and evaporated to
dryness to give l-methyl-3-phenyl-5-(3-trifluoromethylphenyl~-
4(lH)-pyridone, m.p. 153-155C.
The following example illustrates the synthesis of
a l-unsubstituted pyridone by reaction of a ketone with a
tris(formylamino)methane. To obtain a compound of formula
I, this product is alkylated.
Example 123
A 1.4 g. portion of 1,3-diphenyl-2-propanone was
mixed with 1.0 g. of tris(formylamino)methane in 20 ml. of
dimethylformamide. The reaction mixture was stirred at
reflux temperature for 3 hours. The mixture was then cooled
to approximately room temperature, and poured into water.
The precipitated solids were separated by filtration, and
the solids were suspended in chloroform. The chloroform was
then filtered~ and the solids remaining were washed first
":~
X-4097A -69- ~
. . . :
~75696~
with water, and then with chloroform. The yield was about
100 mg. of 3,5-diphenyl-4(lH)-pyridone, m.p. greater than
335C.
The example next below shows the synthesis of a
pyridone of formula I by the formylation of a ketone to form
a compound of formula IX, followed by exchange with an amine
to form a compound of formula VII and aminoformylation.
Example 124
The formylation of 1 phenyl-3-(3-trifluoro-
methylphenyl)-2-propanone was carried out according to the
method of Example 121. A 5 g. portion of the product was
dissolved in 50 ml. of ethanol, and 20 ml. of 40~ aqueous
methylamine was added. The mixture was allowed to stand
... ... .
overnight at room temperature. The mixture was then evapo-
rated to dryness under vacuum, leaving a-heavy viscous oil.
The oil was mixed with 10 ml. of dimethylformamide dimethyl
acetal, and was heated on the steam bath overnight under a
trap which removed ethanol as it was formed. The next day,
the reaction mixture was evaporated to dryness under vacuum,
and the residue was triturated with ether. The ether
soiution was filtered, and the solids were recrystallized
from acetone-ethyl ether to produce l-methyl-3-phenyl-
5-(3-trifluoromethylphenyl)-4(lH)-pyridone, m.p. 153-
155C.
The following example illustrates the synthesis of
compounds of formula I by the 4-chlorination of a ~;
1 unsubstituted pyridone, followed by 1 alkylation and
hydrolysis.
Exam~le 125
3~ A 39 g. portion of 3-phenyl-5-~3-trifluoro--
X-4097A -70-
:' ' ' . ' ' , ' .' ' ~ ' ' ' " '
~L~7S696
methylphenyl)-4(1H)-pyridone, made by the method of Benary
and Bitter, was refluxed with 100 ml. of POC13 and 5 ml. of
dimethyl~ormamide for three hours. The excess POC13 was
then removed under vacuum, and the residue was taken up in
chloroform. The solution was poured into ice-water and the
mixture was stirred until the mixture reached room temp-
erature. The aqueous mixture was then e~tracted with
chloro~orm, and the organic solution was washed with dilute
sodium hydroxide solution~ and dried. The organic solution
was then evaporated to dryness under vacuum, and the residue
was recrystallized from hexane to produce 4-chloro-3-phenyl-
5-(3-trifluoromethylphenyl)pyridine.
A 2 g. portion of the above compound was dissolved
in 20 ml. of chloroform, and 10 ml. of methyl iodide was
added. The mixture was allowed to stand for four days. The
mixture was then evaporated to dryness, and the residue was
recrystallized ~rom chloroform-hexane to produce pure 4-
chloro-3-phenyl-5-(3-trifluoromethylphenyl)-1-methyl-
pyridinium iodide
A portion of the above intermediate product was
dissolved in methanol, and the solution was made basic with
aqueous sodium hydroxide solution. The basic mixture was
then heated at reElux for one hour, coo]ed, and the solids ~-
were separated by filtration. The product was l-methyl-3-
pllenyl-5-(3-trifluoromethylphenyl)-4(lH)-pyridone, m.p.
153-155C.
The following example illustrates the l-alkylation
of a l-unsubstituted pyridone by reaction with a methylating
agent.
X-4097A -71-
- . . .
, . , ' - : ~ ,,
1~75i6~
Example 126
.
A 8 g. portion of 3-phenyl-1-(3-trifluoromethyl-
phenyl-4(lH)-pyridone was suspended in 30 ml. of chloroform,
and 6 g. of methyl trifluoromethanesulfonate was added. The
reaction mixture was stirred for 3 hours, 10 g. more of the
sulfonate was added, and the mixture was stirred overnight.
In the morning, the reaction mixture was poured into aqueous
sodium carbonate solution. The aqueous mixture was fil-
tered, and the precipitate was washed with additional
chloroform. The organic layer of the filtrate was sepa-
rated, dried over magnesium sulfate and evaporated to dry-
ness. The residue was an oily gum which was identified by
NMR analysis as essentially pure 3-phenyl-5 t3-trifluoro-
methylphenyl)-l-methyl-4-methoxypyridinium trifluoromethane
sulfonate.
The residue was mixed with 30 ml. of ethanol and 3
ml. of concentrated hydrochloric acid, and the mixture was
stirred at reflux for 2 hours. The reaction mixture was
then concentrated under vacuum to an oil, which was taken up
in methylene chloride. The mixture was washed with aqueous
sodium carbonate solution, and the organic layer was again
evaporated to dryness under vacuum. The residue was tri-
turated with ethyl acetate, leaving a precipitate, which was
held and combined with the later-separated product. The
ethyl acetate solution was concentrated under vacuum, the
residue was mixed with 30 ml. of ethanol and 10 ml. of 10
sodium hydroxide solution, and the mixture was stirred at
reflux temperature for 2 hours. The reaction mixture was
then poured into water, the insoluble product was removed by
filtration, and the solids were recrystallized from acetone.
X-4097A -72-
1L~75~96
The product was l-methyl-3-phenyl-5-(3-trifluoromethyl-
phenyl)-4(lH)-pyridone, m.p. 152-156C.
The following example illustrates the use of a
formate ester aminal as an aminoformylating agent in the
process.
~xample 127
A 15 g. portion of 1-phenyl-3-(3-trifluoromethyl-
phenyl)-2-propanone was added to ~n ethyl ether solution, at
ice bath temperature, of 70 g. of (t-butoxy)-di(dimethyl-
amino)methane. The mixture was warmed to evaporate theether, and was then heated on the steam bath for 2 hours.
The volatiles were then evaporated under vacuum, and the
residue combined with 15 g. of methylamine hydrochloride, 40
ml. of 40~ aqueous methylamine and 200 ml. of ethanol. The
reaction mixture was then heated on the steam bath for 6
hours, and evaporated to dryness. The residue was taken up
in water, and extracted with methylene chloride. The
organlc layer was washed with water, dried, and chroma-
tographed on a silica gel column with ethyl acetate:benzene.
Collection and evaporation of the product-containing
fractions gave about 0.9 g. of 1-methyl-3-phenyl-5-(3-
trifluoromethylphenyl)-4(lH)-pyridone, m.p. 152-156C.
The next example shows the use of a formiminium
halide for aminoformylating the starting propanone.
Example 128
The aminoformylating reagent was made by adding 30
g. of dimethylformamide dropwise to 20 g. of phosgene in 150
mlO of chloroform at 0C. A 10 g~ portion of 1,3-bis-
(A~-chlorophenyl)-2-propanone in 50 ml. of chloroform was
X-4097A -73
' '
': ,
~7S6g6
then added. The mixture was stirred for 3 hours, after
which 50 ml. of 40~ aqueous methylamine was added. Chloro-
form was then evaporated from the mixture, and 200 ml. of
ethanol and 50 ml. of additional 40% aqueous methylamine were
added. The mixture was then stirred under reflux overnight.
In the morning, the product was extracted as described in
the example above, and chromatographed on a silica gel
column with ethyl acetate containing successively larger
quantities of methanol. The product formed is 3,5-bis-
(3-chlorophenyl)-1-methyl-4(lH)-pyridone, 0.85 g., m.p.
164-167C.
Continued elution of the column with methanol re-
moved a compound identified by NMR as 4-chloro-3,5-bis(3-
chlorophenyl)-l-methylpyridinium chloride. Hydrolysis of
the compound with a~ueous ethanolic sodium hydroxide solu- -
tion at reflux temperature yielded additional pyridone
upon dilution with water, filtration, and recrystalliza-tion
from acetone-ethyl ether.
The next example illustrates how l-acetoxy com-
pounds of formula I are prepared.
Example 129
A 2.4 g. portion oE 3,5-diphenyl-1-hydroxy-4(1H)-
pyridone was made by the process of Example 29, using
hydroxylamine as the aminating agent. The pyridone was
added to 25 ml. of acetic anhydride and the mixture was
heated on the steam bath for about 1 hour. The volatiles
were then evaporated under vacuum, and the residue was
washed with benzene and then recrystallized, first from
benzene and then from chloroform-hexane. The yield was 2.1
g. o~ 1-acetoxy-3,5-diphenyl-4~lEI)-pyridone, m.p. 197 199C.
X-4097A ~74-
,
~756g6
The following typical salt compounds were prepared
by making the free base compounds according to the general
procedure of Example 29, and forming the salts by contact
with the appropriate acids in aqueous solvents.
Example 130
l-methyl-3,5-diphenyl-4(lH)-pyridone, hydroiodide,
m.p. 110C., yield 100
Example 131
l-methy]-3,5-diphenyl 4(1H)-pyridone, hydro-
chloride, m.p. 187-194C., yield 100~
The example below is typical of the formation of
pyridinethiones of formula I.
Example 132
A 10 g. portion of 3,5-diphenyl-1-methyl-4(lH)~-
pyridone, prepared by the process of Example 1, was mixed
with a 10 g. portion of P2S5 in 100 ml. of pyridine, and the
mixture was heated under reflux for 2 hours, after which it
was poured into a large amount of water and stirred for one
hour. The mixture was then filtered, and the solids were
recrystallized from ethanol to yield 9.8 g. of 3,5-di-
phenyl-l-methyl-4(lH)-pyridinethione, m.p. 168-171C.
The following typical pyridinethiones were pre-
pared by following the general procedure of Example 132.
Example 133
3,5-bis(3-chlorophenyl)-1-methyl-4(lH)-pyridine-
thione, m.p. 210-212C., yield 86%
Example 134
.
3-l3-chloroPhenyl)-l-methyl-5-phenyl-4(1H)-
pyridinethione, m.p. 190-193C., yield 71~
X-4097A -75- -
,
,. ' '
..... .- - - . . . - . : .. :: -
~Ll)7~69~
Example l
l-methyl-3-phenyl-5-(3-trifluoromethylphenyl)
4(lH)-pyridinethione, m.p. 210C., yield 70
Example 136
The compounds of formula I prepared in Examples
1-23 can also be prepared by the process of Example 29.
Example 137
._
The compounds o~ formula I prepared in Examples
24-122 can also be prepared by the process of Example 1.
The compounds of formula I described above have
been tested in a number of herbicidal test systems to
determine the range of their herbicidal efficacy. The
outstanding results produced by the compounds in the re-
presentative tests reported below are exemplary of the
outstanding activity of the compounds.
Compound application rates are expressed in kilo-
grams of the compound per hectare of land (kg./ha.) through-
out this specification and claims.
Blank spaces in the tables below indicate that the
compound was not tested against the named species. In some
instances, the results of testing a compound repeatedly
against a plant species have been averaged.
Untreated control plants or plots were included in
.,
all tests. Ratings of the control produced by the compounds
were made by comparison of the treated plants or plots with
the controls.
In the tests of Examples 138-142, plants were
rated on a 1-5 scale, on which 1 indicates normal plants and
5 indicates dead plants or no emergence. A 0-10 rating
X-4097A -76-
~756~6
scale, on which 0 indicates normal plants and 10 indicates
dead plants or no emergence, was used in the tests of
Examples 143-145 and 1~8-150, and the tests of Examples
146-147 and 152 were rated as percent control of the plants.
Rating scales used in the tests of Example 151 are indicated
in the description of the example.
Example 138
~road spectrum greenhouse test
. .
S~uare plastic pots were filled with a sterilized
sandy loam soil and were planted to seeds of tomato, large
crabgrass and pigweed. ~ach pot was individually fer-
tilized.
Test compounds were applied postemergence to some
pots and preemergence to others. Postemergence applications
of the compounds were sprayed over the emerged plants about
12 days after the seeds were planted. Preemergence appli-
cations were sprayed on the soil the day after the seeds
were planted.
Each test compound was dissolved in 1:1 ace-
tone:ethanol at the rate of 2 g. per 100 ml. The solutionalso contained about 2 g. per 100 ml. of an aniGnic-non-
ionic surfactant blend. One ml. of the solution was diluted
to 4 ml. with deionized water, and 1-1/2 ml~ of the re-
sulting solution was applied to each pot, resulting in an
application rate of 16.8 kg./ha. of test compound.
After the compounds were applied, the pots were
moved to the greenhouse, watered as necessary, and observed
and rated about 10-13 days after application of the com-
pounds. Untreated control plants were used as standards in
every test.
~-4097A _77_ -
-' ~ll.C3756~
The table below reports results of testing typical
compounds of formula I. The compounds a:re identified by
their example numbers above.
X-4097A -78-
::
~ :
56~
I ::
3 r~ ~ N t~l r~ r~7 ~r ~r ~1 el' ~ ~ ~
.~
a) ~n
~ ~ ~ ': ''
a) t1~ ~1 . .
l , . .
~1 ~ In In ~ Lf~ ,
E-l .
'I t " .-: .
~1 ~ ~:
~,1 3
~ , , .
a~ a),ll
~ ~ h
~ U ; ~''
P~ ~
~ ~ ", , .
a) ~ .' ' :'
o ~ U~ n o ,1
X '::
C~ ~ ~
X- 4 0 9 7A - 7 9 - .
~.'
,: ~ ','
3~75~ 6
3 ~ ~
.~
a~ u~
U
a~ ~1
~a
~0 0
.~
E~
a
,
G
O
~1 .~ . . '
~ ~ ~ ~ '
~1 U ~ ~ .,
E3 C) . .
O
a)
~ ~ I
El ~'':
q~ ':':
O
a)
.
p, .
O o~ o~ o ~ ,~ o
X Z ~
,
X-4097A -80-
~75696
~1 . .
.~, '.
Q~ u~
c~ tn
~ ~ td
O ~
E~ h
U~
~0 O
~ ~ U~
E~
~ : ' ,
.,1 . .
~ a
O O
,~ .
a
,~ U~
td ~ U~ . '
E~ C~
a) h ~ ~r ~r u~ ~r ~r ~ ~r ~ ~ ~1
0 h
P. O ,'
E~
O
a~
~ x æ
X-4097A -81-
. - - - . . . . .
t75696
~1 .
3 ~ ~ ~ ~ ~ ~ ~ ~r L~ ~ ~ ~ ~ In
.~
a~ u~
~ ~ s~
~ td ~ ~ ~ ~ ~r ~r N ~1 Lf I U~ ~ N ~1 `1 ~ . :
E; ~_1
P' l .
Ei~
E~ ~
~ ' .
~ ''-'.
.~ ~
) . ~ ~ ~ ~P ~ ~r ~ ~r 1~ ~ ~ N ~
~ ~I) ~
tD 4 In ~ ~ N ~ ~r '
Q)
o
~ ~ a4 l
o
a
~l ~
:) ~ O o ~ 0 0 1~
X-4097A -82-
~CJ 7S69
~1
'P~
~ tn
~ S~ ~ ~ ~ ~ er ~r ~ '
s I ~ .4
~ ~ ~ :' ~
U)
o ~ ' ' '.
O ~ ~ ~ ~ ~ N
: ;
::3 ' ::
.,1 ' :
O ~ r N ~ N
~ a) ~ .'
~: ~ ~ N ~ U~
h ~ Q
e c~ . ~-:
a~
o ':
E~ .'~
:.
o
: :''
~ ~ . -: '
O ~
- o ~ Z; ~ O ~ ~.
U ~:
X-4097A -83- -
.' .
'. ' .
. . .
7S696
Example 139
seven-species greenhouse test
The test was conducted in general like the test
described in Example 138. In this test, the seeds were
planted in flat metal trays, rather than in pots. The com-
pounds were formulated according to the procedure above,
except that about 6 g./100 ml. of the compound was dis-
solved in the surfactant-containing solvent, and about 1
part of the organic solution was diluted with 12 parts of
water before application to the trays. The compounds were
applied at the rate of 9.0 kg./ha., and the results of
testing against the species named below were as follows.
X-4097A -84-
3L(:1 75~
F uu F z N ~ ~ ~1 ~ ~ N ~
.11~ : ::
-fjU
~eal~aAlal~ ~ Nr~ 1 N ~
~1 ." .", . ..
~ I F e ~ x ~ ~N r~) N ~ ~ N
O paaM~Fa ~ ~ ~~ N N ~) N
sselfjq~ ~I N ~
N UJ.O~ ~IN _IN ~ r-l ~) N ~ : ~
a)
R . : .
eFuul z ~I N N~I r-l~1 ~ ~ ~ : `
~:rlE~ ~ ~ ~ ~ ~Ir-l N r~
a) _~uFu~o~ . :;
~ ~ea¦~al~Tal~ N N N~1 ~ i ~ N N
Ei IFe~xo~ N ~ ~~I r~ ~ N
a~ Fa ~P ~ N ~
aJ~ ~r ~ ~ ~ ~ ,~ ~ ~ ~r
U~O~ -I ~ ~~1 ~ ~ ~ ',. . ..
~ .
o z .
O ~ ~`:J ~ ~ N ~I ~ tv) ~ ~"
C~
X 4097A -85-
~075G96
~FUuF 2 <~, ~ ~, " ,~, ", ~ ~ ~ :
~lfj N ~ ~
_~uFu~O~ .:
~ IF~xo,~ N
o P~Fd N 1`'1 ~ ~ d'
~ SS~ qE~l~) N ~ ~r N ~ ~ ~ ~r ~ Ll't
~ ~ q : '' '
U10~) ~ 1~ er N ~ d' ~ ~ ~) ~)
C~ ,:'
--I ~FUUF Z N ~ t~) ~I N N ~ l N ~1
R
E-l ~IOIf; N N ~ ~ Lt~ ~ N N
u -fjUFulo~
1: ~ a¦ ~OA¦~3A ~ ~ 7 N N
IFe~xO,~ ~ r N ~)
pa~ Fa ~ u~
ss~l~qel; ~ ~ ", ~ ~ ~p ", ",,
u~o;) ~ ~ 'r ~ N
'~
4~ ~
O O
æ
~ ,~ ~ r~ o ~1 ,~
O Q. N ~ '1
O X
il
X- 4 0 9 7A - 8 6 -
. . ~ , . ,
lL~75696
UUFZ
~1015
~_~uFu~ow
h `~eal~AIa~r~ ~ u~
~IFe~xo,~ ~ N
OpaaM~a ~ Ln
ss~q ~;) ~ u~ ~ ~ ~ ~ N ~ r~
3 u~o;~ ~
~1 ~FUU
~ ~1~ ~
a~-~uFu~o~ : .
~Fe~ 3AIal~ ~
~IF~xo~ ~ ~ ~ ~,. ~, ~" ," ~, ~ ~ ..........
S~paa~Fa ~ ~ ~ ~r ~ u~ ~P ~ In ~
sse~q~ ;~ ~ ~ ~ u~ ~ u, ~ ~ u~ u~
U10;)
4~
O O ..
O ~
~ ~ 0~ ~ .
V ~
- X-4097A -87-
... ' ',.
1~75696
~FUUF Z ~ ~ ('~ ~ ~ ~ ~ ~ '~) ~ -
~101~6
a~_~ulu~o~
h~1?a~ AlaA t~
~I F~Xo,,a ~ ~ ~'
Opaah~F a ~ ~ ~ ~ ~ ~ ~ ~ ~
ss~l~qel~ ~ ~ ~ ~r ~ ~ ~ ~ ~r ~ '
-:
U~O~ ~ ~ ~ ~ ~ r~
o
.
UUFZ ~ ~ ~ n
R
E~ ~101~ u~ In LO U7 LO In ~r ~ Ll~ In
a) -fjUFulo~ , .'
~~F e ~ 3A I ~ A u~
h
e~xo~ u~ In ~ u~ In u~ n u~
p~3a~Fa u~ n
s s~q~? ~n u. ~ ", "~ "~ ," ,~, ", "~
a~
: uloa
~
: ~ oz
~a
a~ ~r Ln ~ r~ oo ~ o ,7 ~ ~
o ~c ,
X- 4 0 9 7A ~ - 8 8 -
'
...
: .:
, , , ~, ; . .
.. . . . . . .
1~56g6 '
UUF Z
olÇ
~J -ÇUFU~O~ ~ ~ ~ ~ ~ ~ ~ ~`l N
~:; ~Feal ~a~ '~ ~ ~ N ~
~ IF~xo,~ ~ N ~
O paat~ÇFd ~ ~ l N ~ ~
ss~çq~
3 a~l~q ~ N r-l ~ ~ _l e~ ~ ~ ~ ,.
O u;roo ~ ~ l N -1 ~ t~l ~1
N
a) ~FuuF z "~
: .q ~lÇ ~ ,
-ÇuFu~o~ ~
c~ ~FeaT 1~3A~ ~ N
IF~xo~ u~ ~ ~ Ln In ,I Ln ~ ~r u~
~1 PaaMÇFa ~ u~ N ~
PJ , .
ssel~qe
a~q u~
. U~O~
" ,,.
x ,: ,:
~ ~ ..... ..
o ~ ,... .
; X- 4 0 9 7A : - 8 9
~ :
' ~ ,,' ~,
, , .; ~ -,.~ . .. . ,, . . ;
~ ~, , : . .: . : ,:. . ...
-
~756~6
Z ~ ~ N ~ t~J ~ ~ N t~ ~)
~:lf~l . ,
--~UFull~ r~ ~ ~ ~ N N ~ N ~ ~
a) ~F ~ a l ~ 31~1 a A
~xo,~
paa~Ta ~ ~ ~ ~ N
ss~l~qel~
~ ~ '1 ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ..
~1
U10~ ~ ~ ~r ~ N ~ N t~
. ~IUUFZ r~
. E~ --~UIU10~ ~I N t~1 ~ ~ ~ N ~ ~ ~r
t~ ~B~T:I a~l3A
Fe~xo~ ~i ~r ~r u~ ut u~ ~ ~r u~ ~ , .
P~aM~Fa ~ ~ ~ U~
SSelhqB;r;~ : :
U~O;) ~I ~~
O ~ , ' ' '.
O
,1 o ,~ ~ ~ In ~ ~ u~ ~D
x~ 4 0 9 7A ~ 9 0~ ~ :
:
'
.. . , . .. .~ , . . . . . .
~7~696
eFuuF z ~ ,1 ~ N N N N ~) t~ N
~lolh ~ N ~ ~ N ') N 1` '7 N
c: -.6uFuxo~
~eal~aAlal~ ~ N ~1 N N ~ N ~ N ~1
~ ¦Fe:¦.XO~[ ~ ~ I N ~ ~ ~ ~ N
O p;3ah'~EIFd ~ N er N N N ~ ~ ~ N
ss~qel;~ ~ ~ er N N ~1
~ a~eq
,~
u~o~ er N ~r N N ~ N ~ ~ N
N
eFUuF Z ~ N u) ~ 1~ tn ~r
E~ ~1
O -~UFU~O~
a) ~ e ~ l ~ a~ l a
IFe~X~ ~ ~ N U~
P~ F a Lr~ r r~
ssel~qe~;) , u~ n
U10;) n ~ U~ N u~ n ~
O o
..
~ ~1 ~ o r~
X-4097A -91~
:~'75696
UUFZ
~10
-~UFU~O~ ~ ~ ~ ~ ~ ~ 'I
~a~ A ~ ~ ~ ~ ~ ,~
3 IFe~xo~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~
~pa~ a ~ ~ l N ~1 ~
~: ss~q~ ;~ er
.,~
~ U10;) ~ t~
~`J :',
~ ~TUUFZ u~
--~iUTUlo~
~ -~eal~aAl~A
~I re:~xo,~ ~ In ~ N r~l
s~ . pa~3~6Fa
ssell;q~ 1'~ 1~ u) u) Lr) ~ r-l ~ (~ U~
U~O Lt ) N ~ 1~ l N
:
.
Q æ
1 ~ O -1 N ~ Ll~
C~ ~C
X-4097A -92-
,' " '' ' ' . , ": :' ' . ~ '' ' '
.
~L~)7S6
eluulz ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ N
~101~
_~Ul Ul oT~ r ~ ~ N ~1 ~1 r-l ~1 ~ ~1 :~
~l~A
~3IF~xo,~ ~ ~ ~ -I ~ -' ~ ~ '
Op~M~Fa
ssel~qe~; ~
U:J;O~) ~ r) N ~I N r-l t~l ~ ~1 ~ ~ ~
O ~':', "~. ',. '
t~ ~`, , .
~FUUF ~ ~ ~ In ~ ~ ~ ~ ~ ~ ~ In
E~ a~--E'UTUIOW~ ~_1 "~ "~ ~1 ~1 ~1 0l ~ ,1 ~ u~
hIF~XO~ ~
. , :':
pa~ d :,;
S S E!1 6q~ : .
~1 ~ ..
Z `
~ a)
y r-l O ~D 1~ a~ o ~-~ ~) N
X-4097A -93-
:. , :~. .
~(~7S69~
~FUUFZ ~ ~ ~ ~ ~ ~ ~ ,
U --fjuTulo~ ~ ~ ~1 ~1 ~`1 ~ N r~
a~laA ~ ~ ~ ~1 ~ ~ ~ ,~ ~ ~ ~ :
~ I F~XO~
o P~fiFa : :
C SS~lfiq~l~ t'`l ~ ~ ~ N ~1 d' N r~) t'`l t~l ;
~ U~XO~) ~
. , ' ~.'' '
Q ~FUUIZ ~ ~ ~r ,~ ~ ~ In ~ ~ ~ ~r
E i --fiUTUlo~ ~ ~ ~ ,~ N ~ U') ~
~ ~F~?al~ 3A ~ I N r-l Lr) .
l~xo,~ er
pa3~d ~ u)
ss~fiq~ Ln n Ln ~ ~ ~r n ~ Ln
~ .
U100 ~ n ~ r) Ln
.
O O
~ Z ~' ' ' , ' :'
n ~D
O ~ o o o o ,t ~ ~ ~ ~ ~I
C~
X 4 0 ~ 7A ~ - 9 4 _
:
' :
: ~ ~ . .... ..
,
~L~75i69~
Example 140
multiple-species greenhouse test
.
In general, the test method was the same as the
method of the test above. Various compounds of formula I
were tested preemergence and postemergence at different
application rates which are indicated in the tables below.
A number of additional weed and crop species were used in
the preemergence tests as is shown in the -table. Typical
results were as follows.
X-4097A -95-
~75696
UU~ Z ~`J N r~
~IOIElfjUTUlo~ ~ ~ ~1
pa~l~UOsluFr Nt~ I ~ ~1 tr) N
AI~3A
~0 PIIM
X ~ ,!I ~r) ~rN ~ ~1
paa~ld ~
p;r~ sn~ N r~7~1 ~) ~ ~ ~ ~ ~ ~ .
s s~ el~) ~ r N el' L~l
.
?nE: squl~l ~
SS1~19
p~:e~ul~ : :
O~U10~, ~ ~ ~
v l~qum;:)n; ) ~ N ~1 ~ 1 ~ ~ t~l N ~r
s~ a;: F~ ~ -~ ~ N
E~ ~ ~aa l~ns ~ ~ ~ ~ ~ r~ ~r ~ N
IM ~ N ~1 ~ N ~ ~ t~
u~aq~oS ~ ~ N
U0 ~ ~0;)
UlO~ ~ ~--I ~r,I N ~ ~1
4~
O ~ 1~ .:
--I ~ ~
Q~ ~Ir~ N N N~-I ~I ~I N ~l
4~
O O
Z ~ .
X- 4 0 9 7A - 9 6 - ~ ~ .
: : '
:~.
:- , ::
. .. . . "., . . - . .... . . .. .. . .. ..
-:: .. . ,. . : . . . . ~ . - .
~75~
-eFUUF Z ~ ~ Il~ ~ r) ~ t~l N ~
ol~uFU~O~ ~ ~ N
paa~uoSUlFr N ~ r ~ ~ d~
~: ~ a ~ ~ aA l i3 A
'rFM ~ ~ 11'1 (~ N ~ ~ ~ ~r
IFe~X.~[ ~ ~ n ~r ~ u~ ~ ~ ~r , .
pa~ d ~ "~
ple~ sn~ ~ ~ u~
~ leq
enE~squ
sse~g ~ u~
ple~ule~[
~c~ o~eulo~
,~ a) :.
::1aqum~n; ) ~ ~ u~
~F~ ~ ~ ~ ,~
, ~ ~ns
e~le~FI~ ~ In ~ ~ ~ ~ ~ ~7 ~r . .
~ ea~M r~ ~ ~r ~ N ~ ~ ~ ~r
u~2q~0s ~
uo~ o~ r~
U10;) 't' ~r ~r N N ~ ~ t~1 ~
~
a~ Q.~ t`l ~1 ,-1 U') ,-1 ,-1 t~ r-l r-l
r~ r~ O O O ~ O r~
O O
~ ~-1 ~ OD ~ O r-l ~ ~ N
X~4097A -97~
'.
,.,.,:
56~
e F u u I z - ~ ~r N N ,r~ ~ ~ ~ N Lt~
ol~ulu~:o~ ,~ ~ ,I N ~ ~r ~ (`1 ~ u
p~ uosullr ~
~a~ A ~
:1 eo PI IM ~ N N N ~ In N
IFe~xo,~ ~
paa~l a ~
pl~sn~ ,, u~ ~ In In ~ ~ ~ ~ U) ~ .
. sselfjqe
sse~g
~ pl~liule~[
,~ . .
~ o~eulOL ~ ~ N ~ Ul U~ ~ ~ ~ Lt) ,
U O
qum::~n;) ,~
a ~ F ~ ,I N _I r l N ~ N N ~1 '1
E~ ~ ~ e~nS ~ ~ N ~ u~
P~ e ~F I e ~1~ ~ ~ N N 1~) U) ~) N ~) In
~ ea~M
ue~ oS ~ N ~_1 N 'S ~ N N ~r
UO~ O~ ) r l r~
U:J;O~) --1 ~) ~I N d' ~ ~ ~) N L~7
.
O ~ ~ In ,
~ ~ ~I N r--l O ~1 It ) N 11~
:r;'¢,y ~ o c:~ o ~1 o o o o .
O O ' ~
~Z , ~ '.
a)
~ r-l ~ ~ U) ~D r` 0~ ~ O N N : :
U X
X-4097A -98- :~
.
. ~ .
. : : , ,,,. , , . : .
. ;'
-: - : ~ . . :. :
, : . . :: , :
,, ~ .
1~7~696
,,,
uul Z ~ U ~, ,,
~ol~fiuFu~o~
p~uosul~r ,~
~Fea~ N ~ N
~eo PTFM ~ ~ f~
I F e~ x
P~Fa
p~sn~
SsB~l~qBl0~ L~
a~leq
en~squl~l , ~r ~ ~ .
SSB.19 ~ u~
p~e~ule~
o~eu~o,I~ ~ ~ ~ r~
~o ~ ~ laqum~n; ) ~ 1
h
~ ~ ~aa IB~
E~ ~ e~le~l~ ~ u~~ ~ ~ ~r ~ ,~
:~Bat~M ~ ~ 1 ~ (~ N ~ ~`1 N/~1 ~ -
UB~q~SOS ~ 1 ~I N ~I t~
UO:1 :1 o~) r~
U~O~ ~ ~ ~ ,~ ~ ~ ~ ~ ~,
' :' ' . :- '.
1~ . . ' -' :
O ~ U~
o o ~ o ~
y o ~ o o o ~ ~ ~ o o o ~:
o o
a Z ,~.. .
~ _I ~ ~ ~ ~ ~ ~ r~ cr. o o ~1
:' : ~ :
X- 9 0 9 7A
':
:' .
7~696
uuF ~ ~ ~ ~ ~ ~ ~r ~ ~ N
~o~uFu;~o~ ~ ~ N ~ ~ ~r
p~MuosulFr ~
~e~l~a~ ~ ~3 ~ ~ ~ ~ ~ u~ . ~ ~r ,t
~0 PIFM ~ ~ ~ ~ ~ ~ 7 ,t ~ ~
xo,~ ~ n ~r ~ ~ u~ ~ ~ ~ ~r ,t
P~a~Fd ~ t N
p;l~sn~ ~ ~, ,~, ~ ~ ~ ~n ~ ~ ~
SS~ q ;) ~ u, ~ ~ Lr) u~ ,t
n~squlel ~ ~ ~r ~ ~ ~ ~ ~ N ~ ~
ss~g ~ ~ ~ ~ ~ ~ ,t ~r ,t
'a pll~l~UI~ ~
~ o~ L ~ ~ ~ ~ ~ ~ r ,t ~r ,1
o ~ l~n~n; ,t,~
r~ h~ a::)F~[ ,t , t ,1 ~ ,t ~ ~ ~ ~ ~ ,t
a) E~ ~a~ ns ~ ~r ~r ~ ~ u~ ~ u~
~3
~-ea~M ~ N ~
u~q~oS r~
UO~:~o~ ,t ,1 ,1,1 ,1 ~t ,1 ,1 ,t ,1 ,1 .
U.xO~ ~ t ~ ~ ~ u~
.:.
O~ : ::
,1 In ~ ~o ~. o ~ Ln ~t ~ ~ ~:
~1 ~ O ,t ;~:
. ,
O zO .
o x
X-4097A -100
:
.. ' .
~L~756~6
~FuIIFz r~ N Ir~ ~I N N U) ~ ~J N
N 1~ ~ N N It~ ~ ~r N N
paaMuosulFr ~ N Ir~ N N ~ 1~1 ~ N N N
~a ¦ ~ a~ N N 10 N ~1 t`~
~0 PIFM N N Ll) rl ~1 ~ 11~ N ~I N N
I F e~X~
pa~ Fa N
p~ sn~ N U~ Il') t~) I~ Il') Ir) ~ ~I ~ t'~
S S~ qB;~;)
a5~ u~
~a~nE)squ~l ~ n ~ ~r ~ u~ ~ ~ ~r
S S ~ ) ~ ~r In N ~ ~) n ~r
p~u~e5 [
:~1 O~ OL ~ N In ~ N ~r L~ ) N N N
,~ a~
aqum~n~ N N Cl' r~ ~ ~) Ir) ~ N N N
O (I)
c~ s~ a ~ ~ ~ ~ N ~) ~ ~ N ~ N ~1
:) ~ :~aa ~ nS N
P~ ~ ~1 e ~1~ N N In N ~ ~) 1~ ~ N N
~ea~M N ~) 1~) r-l ~ r~) Ir) ~ N r~
u~3q~oS ~ ,1 ~r ,1 ~ N ~ ~ ~ N N
UO ~O;)
U10~ ~ N ~ r~ N ~ u~
.~ :
. .
O ~ ~ C~
r~l L 017 ~I W ~ ~
P~ ~ N O In r~ N L~l r-l ir~
~ ~.X O ~ ~ ~
O O ,
Z
a
O ~ ~ o ~IN ~r C~
o x
o ~
X-4~97~ -101- - -
. . . ~ . . : : .
~)756~6
~IUUF Z ~ ~ ~ ~ u~ ~ ~ u~
~10166UFU10~ ~ -~
pa31~UOSulFr N N ~r ~r 11)
e~l~al~lal~~ ~ ~ ~r u~ ~ ~~r ~ ~ ~ .
~eo PIFM ,
XO,~~7 ~ u~ ~ u~ ~ ~~n
pa~M6F au~ ~ In .-. m ~r ~r~ ~ ~
ple~sn~ ~ ~ ,," ~, ", ~, ~",~, ,," ~,
s s ~ ~ 6 qe
~6
~a~len~SqUIel~ n ~ ~ I
S S e19t`l
p.I~Ull~
~ . . '
:~ O~ O,~ ~ N ~U') ~1 ~
aqum~n~ ~ ~ ~ "
F~ " " ~ N
~a~ ~e~nS r~
. ,
~ea~M ~ ~r u~ N ~ N N ~ t~
u~aqAos ~ ~ ~r _l ~ ~ ~ N
UO~ .O~ ~
UIOOr~l~t ~1 N ~ ~It'~ I N
'
. .
O ~ ::
$ Q~ ~ ~ ~ ~ ~ "'. '
'¢ N O O O ~ O . ~ ~
~Z;
~:
~ ~ ~ ~ ~ ~ I` o ~ ~ ~r '~D ' ~ ''
O ~ O O O O O ~
O X ., .
~::
: X- 4 0 9 7A ~ -10 2 - ~.
: - :
.
1~7S6~6
~ ~ ~ ~) ~1 ~) N N ~ ~ ~ ~ N
.,1
O
~ ~ N ~ N N N N ~) ~) ~) ~1 N t`l
O
a~
~) ~ ~ N N ~ ~ ~ ~ ~ ~)
a)
~1
. tY~ N ~1 N ~I N N ~' ~ ~I N N ~ ~ ~`
a) ~1 ~ . :~
Ei Il) , ,:,
E~ ~ 3 ~:
O ~ 1 ~) N r~ N t~l ~ ~ ~ ~ ~`I ~Y ~ .
~1 ~ ..
'
U~
tn
J
~ S~
S~ ~ ~) N ~ N ~ N N ~ ~ N N N ~:P
~11 .4
,~ ~ ' '
~1
O N N ~ N ~ N ~I r~) ~ ~ N N
, . ~: ' ,
~ . . : : ~
O ~ ~
~ ~ . ,:
(O P~ ~ ~ N N N ~1 -1 N N N 1--l ~I r-l r l
.' tS~ N N N N r-~ ~I N N N ~--1 ~1 ~1 _1
.`:
. ~ . ..
O O
~ a~
X--4097~ -103
'
,: : . : . .
; ~' :: '
- .- .
69~
.,~
~ ~ ~ ~ r~
.,,
M
O
.'
~
,
::
,0 ~.'
~ " ~ ~ ~ ~ ~ N ~ ~ ~ ~ :
r~ .
~ ~ ''
.ri ,:.',
X
r t~l : '
u ~ a) ::
~ O rl ~) N ~ ~ N t~ ~ ~ ~1 ~) ',
r ~
R
E~ ~
s~ ::
~1
' ;' ~ '~,
W . .
O ~ ~ ' ::
.:
4~
o o
~ z
~rl ~ r~ `
o x
c~ ~ ~ .
X-4097A -104-
,.~. .. .
.
75696
Example 141
-
yellow nutsedge test
Typical compounds of formula I were evaluated in
the greenhouse against yellow nutsedge in a test method
which followed in general the method of Example 138, except
that the acetone-ethanol solution contained about 1.5 g./100
ml. of the test compound, and one part of the organic
solution was diluted with 9 parts of water before applica-
tion. Both preemergence and postemergence tests of the
compounds were made, at the rate of 9.0 kg./ha. The results
of testing these typical compounds are presented in the
table below.
X-4097A -105-
~L~75~96
Table 5
Compound
of
Example Preemergence Postemergence
No. 9 kg./ha. 9 kg./ha.
24 2
2 1 -
26
.
27
29
31 4
32`
33
34 4 ;~ :
36 3 ~ :
129 1 ~-
37 5 4
38 5 4 ::
,
39 1 1
41 5 4 ~.
1 5 5
43 5 4 ~. :
: . 44 3 2
3 2 .
46 4 2
47 5
48 5 4
.
~ ;X-4097A~ 106-
,
.
.. . . .. :.. : .
1075696
Table S Continued
_
of
Example Preemergence Postemergence
No. 9 kg./ha. 9 kg./ha.
49 3 3
4 4
51 5 5
52 3
132 2
2 4 4
.
~ 3 3
3 3
6 5 5
7 5 5
8 S 5 . :
9 5 4
11 2
. 14 5 S
- 15 4 3
28
53 4 4
54 3 3
56
57 5 4
58 1 2
: 59 3 3 . ~ :
: 61
X-4097A -107- :
~ ~ '
:: '
~. :
~4~7S~6
Table 5 Continued
Compound
of
Example Preemergence Postemergence
No. 9 k~./ha.~ kg./ha.
130 4 4
131 3
133 3 3
134 4 3
135 5 4
63 2
64 1 2
66 5 4
67 5 5
68
69 ~ 4
2 2
74 5 4
78 3 3
79 5 4
1 2
. ~1 3 2
87 5 . 2
89 5 4 :~
17 2
:18 2
'
X-4097A -108-
...'.' '-
:., ~ : ,',
,: . ~ . ., . , : , , .: : .
., . - . . . . . .
,. . . -, ~ . . .. .
:1~7S696
Table 5 Continued
Compound
of
Example Preemergence Postemergence
No. 9 kg./ha. 9 kg./ha. _
19
2 2
23 3 3
102
103
105 4 3
106 3 3
107 5 4
109
110 1 2
111 2
112 4 4
113 1 2
114 1 2
116 . 4 4
~: X-4097A -109-
,,:
~ ,
~75696
Example 142
broadleaf weed test
A number of typical compounds of formula I were
tested in the greenhouse against broadleaf weeds which are
representative of families of weeds which exhibit resistance
to many known herbicides. The test method was generally the
same as the method of Example 141, exceE~t that only pre-
emergence applications of the compounds were made~ All
compounds were tested at 9.0 kg./ha.
Table 6
Compound
of Garden Black
Example Huckle- Sickle- Common Prickly Night
No. berrypod Ragweed Sida shade
24 3 2 4
4 3 5
26 ~ 2 3
27 2 1 2
29 2 2 2
3 3 4
31 5 5 5
32 2 5 4
33 2 3 2
34 5 5 5
3 4
36 5 2 4
129
37 5 4 5
38 5 5 5 -
:
X-4097A -110-
.
,, - . . .
~6~7569~
Table 6 Continued
Compound
of Garden Black
Example Huckle- Sickle- Colmmon Prickly Night
No. berrypod _gweed Sida shade
39 3 2 3
41 5 5 5
1 5 5 5
43 5 5 5
44 3 3 4
4 5
46 5 4 5
47 5 5 5
48 5 5 5
49 4 3 4
4 3 3
51 5 5 5
52 3 4 5
132 3 3 3
2 5 4 4
4 5 2 4
- 20 5 5 5 4
6 5 5 5
7 5 5 5 . :
8 5 5 5 .. :
9 5 5 5 :~ :
~ ::
11 4 3 4
14 5 5 5 ~--
3 3
28 3 1 2
; ;~ X-4097A -111- ~
' ;. . :
107S69G
:
Table 6 Continued
Compound
of Garden Black
Example Huckle- Sickle- Common Prickly Night
No. be.r~y_ pod a~weed Sida shade
53 5 4 4 . :
54 5 2 3
56
57 5 5 5
58 3 2 5
61
130 5 s 5
131 5 5 5
133 4 2 3
13~ 5 2 4
135 5 5 5 ..
63 3 3 3
64 5 4 3
: ~:
~: 20 66 5 5 5 ~
68 2 1 2 . .
69 5 5 5 ;
74 5 5 5 ~ :
4 3 4 .
78 4 2 ~ 4
~ 2 2 3 :
: 81 ~ 4 4 4: .:
X-4097A : -112-
., :
'
~L~75696
Table 6 Continued
Compound
of Garden Black
Example Huckle- Sickle- Common Prickly Night
No. berr~pod Ragweed Sid~ shade
. _
2 1 2
87 2 2 5
89 5 5 5
2 2 2
17 5 5 5
18 2 2 2
19
3 3
21 2 2 2
23 5 2 5
102 3 1 2
103
105 5 5 5
la6 5 3 5 ;;
107 5 5 5
109 2 1 2
~ 110 3 2 2
111 5 5 5
112 5 5 5
113 1 4 4 - -
114 1 3 3
: 116 5 5 5 . . :
: .
'
:
~ : ' ." '
.
~ X~4097A -113-
.
,. : :.. : :, , - :
~75~6
Example 143
soil-incorporated fourteen-species test
This test was performed to evaluate typical com-
pounds of formula I against a number of crop and weed
species. The compounds were tested in the greenhouse at
various rates as indicated in the table below. In all cases,
the compounds were applied preemergence to the test plants
and were incorporated in the soil before the seeds were
planted. In general, the formulation of the compounds and
planting and observation of the test plants proceeded
according to the method of Example 141, except that the com-
pounds were dissolved in acetone-ethanol at 1 g./100 ml.
concentration before dilution with water for application.
X-4097A -114-
.
1~75~96
paa~UosluTr ~ ~ O u~ C~ O O ~r o ~ c~
~quman;) ~ o ~ o~ o o o a~
a~
paaMfjF a OOD O O O O O 00 0 ~r O
~ ~ ~ ~ _,
UO~:~O~ O O O O O O O O O O O
epFS ~ )TIa u~~ o ~ ~D O O
ueaq~S a~~ o u~ o o _I N 1` L~
~:X) tJ ,''',
~lOIfj ~ I ~ If) O 11') -1 ~ 1` OD ~ : '
--6UTU.10~ cn ~ ~ :
~ea~M O co o o o o ~ u~ o a~
1~1
sse~3 o t~ o o o o oo Ln o cn oo
ple~ule~[ ,~
E~ a~ co~ !n ~D co o ~ ~ ~ ~ x
o~
e Oco o o o o ~ u~ o r~
O PIIM ~ ,~
0S ou~ o
uTe
~allF~ u~ o
I F~Xo~ ~ a~
U100 O ~ O a~ o o a:~ Ir) O ot~ I` ..
'. ' ':
.
~ O ~
~:~ P; t¢ O O o O o O O O O ~1 0
~ .
O O
~ , æ
~) ..
1 ~1~ ~1 ~ 1` 00 ~ O ~ l~J N
~3 ~3 ~ .
X-4097P. ~ -115-
.
-:
`
.
. . , . .: . .
756~6
p~a~uoSul~r
I~ ~ o ~ ~ In o o o o ~
,1 ,~ :
aqumon~ ~ O O O ~ ~D O U~ O O Ln
.
P~F a ~ ,~
~ -
UO~O;~ O O O O O O O O O O -;
epF S ~ a ~ O O ~0 0 ~ O O O O O
, .
ueaq~OS
n o o ~ ~ O U~ U~ Ln O - " " '
o~ oo cr~
` ~101~ In O a) ~ ~ o ~ o o o
-fjUlU~O~ ~ ~ . ~ ` ' ,
D ¦ ~ ea~M ~ ~n o a~ ~ ~ 1~ u~ O ,~
sselg a~ ~g o OD cn x u) In o o ~ :
~ple~u~le~ ,~
'`I .. ' '
~a;:~F~ I~ o o ~r oo 1~ ~ u~ In o
Q a~
~1 ,, .
E~~ PIFM a~ ~n o u~ o u~ ~D o o ~o
cr~ ~ :
S ~ ~n 1~ ~D ~ In ~ ul O ~r
uFel9 o~
Fhi ~ o ~ o
I Fe~xo~ ,~
:.''`
u~o;) ~ u~ o u~ 9 o o o ~D '
.
~; ~'C o o o o
4~ .
O zO
D d ~ ~ ~ ~ ~ ~ o N ,~
O X
u e~3
X-40~A ~ -116'`
:
:
,:':
/ -
~756~6
paa~uoSUIIr
O o a)~ ~1 ~ ~ ~ 0~ 0
~aqum~n~~r o ~00 ~ r~ O O O O O
paaM~F a
a~~
UO~O~ O O O O ~ O O O O O
~PFS ~ F~a ~ o O ~ o ~ o ~ o ~ a~
~ ~ .
u~aq~oS
u~ In ~In o~ ~9 o ~ ~ o o
~D 'I '~
~101~u~ In oo~ co u7 ~ ~ O 00 o~ -
-~UFU~o~ : a~
~a
~ ~ 1M a~ o r~
.~ cn
SS~19 ~ O ~ ~ ~ ~ t~ n o
~ p~u~[ ~ ~1
r~l ~ .
a) a;~F~ 00Ll~ ~ a~~ ~1 u~ f~ ~ ~9 ~ , ,,
~ a~ '' .
0 PI~M ~ O ~ Ou~
0S co ~
UF~;tg ~ ~o
llF~ o~ o
~e~xo,~ . . . ~1
u~o~ a~ o ~ c~o ~ ut ~ u~ o u7
~ ~ o o o o ~ o o o o c~ o
~0 0
Z
,
~ ~ ~ t~ a~o o ~ ~ ~rLr~ u~ ~D ' '
O ~ u~
.
X-4037A -117-
~ . . : . . : :
~7~6g6
paaMuoSw~r O O 1~ o r~ In ~ ~ ' ''
aqum~n; ) o o ~D O O U~ O U~
paaM~Fa o N L~ It`) o ~' O ~ ~
UO ~O~) O O O O O C~ O O O O O ~ '
epFS ~ Fla a, co u~ o~ o o o ~ ~ ~ ~
ue~q~S o o m a~ o co o u~ N
:'.".
~1 ~ a~ o ~ o u~ ~D ~n ~ . .
-~uFulo~
al ~ea~lM o In ~ o c~ o o ~ ~ o
~ sse~g o o ~ o ~ o o ~ oo r- o
o ple~ule~ ~ ~
: ' '
a) a~F~ ~ o o~ o OD O O O ~ O ' '
~0 PIFM o o o o ~ o o ~ o o o
wn~lS o ~ o o ~ o o ~ ,1 o o
UFel9 ,~
llF~ o o ~ o ~ o o a~
~e~xo,~ ,, ., ., .
u~o; ) o o ~ o In o o ~D N 1-l 0
o o o o o o o o ~
:`
o o
Z I~ O
w: .:
X-4097A -118- ~ :
~ ~ ,~ '.' .. :
. . . . . , . - , - .
~L~7S6~
paa~UosulFr ~ o o
n~ o oo a~ ~DO O O
~,
pa~3~Fd ~ cc, a~ o o
uo~o~ O O O O ~ o o
~PFS ~ F~a O ,~ ~ O
. ,~ . .
a~
u~q~oS
O O
~1~ o OD U~ ~ro
-fjU
~,eellM ¦ ~
1:SSe19 1` o ~n ~n o Lr) If)
~p~e~u~e~ ~ ~ ' .
r~l
T~ ~ a~
0 PIFM ~ O ~ a~o o
oS ~ In cO". ,... ,., CD
UFe~9 ~ o~
~IIFW ~ cn a~ a~ a~ ~ co
- I F~xo~ a~
u~o; ) ~ ~ In ~ ,i '
~ co , .
. .
. ~, :
Ln
p;~ o o o o o o o ::
o ~; ::
O ~ o Or Lt~ ~D r
c)w
X- 4 0 9 7A -119 - .
56~
Example 144
14-species_greenhouse test
In this test, the test compounds of formula I
were applied to the surface of -the soil preemergence to the
test plants. Again, the test method was in general the
method of Example 141. Various applicat:ion rates were used
as indicated below, and typical results were as follows~
Different plant species were used in testing different
compounds.
X-4097A -120-
'
7569~i
~aqu~n~n~ rl o ~ o ~D
a~pas~n~ ~olla~.
~aaa ~ns
~lM In O ~ C~ ~
o~ cn
sse~ u) o c,~ o o
-p~e~u~e~[ a~ -I ~ ,
~ U~
a~
o~
o ~ u~ In
~eo PIFM a~
loS ule~
a~
epFS ~ F~d o ~ o a~ o o
~eal~a~lal~ ~ ~ o o ~
ssel~qe~ ~ o o ~ ~o
~a~lenE)squle~ ~ co o o o
O ~ In ~ O n
U10~) . . _1
cs~
o~lpaa~Fd u~ o o ~ o
a)
~IIF~l ~ I~ o In o o o o o o
E~IF~xo,~
paa~UosulFr ~ u~ o co ~ o o o
~1~ ~ ~ o o c: 1~ 0 ~ a~
~ FUlo~ ~ ~
Molle~ a;~FuaA ~ co o o ~:
U~?aq~os ~ ~ ~r U7 ~r c~ ~ co ~ ~ .
paa~fje~ ~.~ o ~.
uo:~o~ o o o o o o o o o o ::
~aqal~[~nH ~ ~ c~ u~ ~ ' . .
U~ple? ,;,,. :
podal~ FS ~ u~
~ ~ ~ ~1 ~ ~ ~ N
ul~
~F a~e~ ~ o ~ o . I ~ o o o o
o~ al dulex 3 1 u~ ~ ~ ~ ~ ~ ,1 ~) r~ a
~F punodulo~ ¦ ~ ~ ~ ~ ~ ~r
X-4097A -121
`
: :
, . . , . , , ~ , : , .
. '' , ~ ' .. ' ,, ,: , . ' . : ~
.
~075696
~ aq~n~n~ o O ~ ~ ~ ~ ~ o
a5pas~n~ MO
~aa~ ~e~nS
~eal~M o o 1~ ~ 1` ~ ~r CD ~ ~r ~ :
SS~lÇ> o~ o 0~ ~ O O o
-ple~u~ ~ " ,~
a::lF~ o o co o u~
~0 PIFM ~ ~ ~ ~ ~ ~ ~ ~ o o
~n~10S uF~
~PFS ~ FIa ~ ~ o ~ o ~ ~ o o o
aAIa~
ss~l~q~la
a~l~nlisqul~l . ' .
U10~ ~ ~ co ~ f') d' o o ~D 1` .:
~¦paa~Fa ~ ~ o ~ o ~ ~ o o o O
xo~ o ~ o 1~ o ~ , o o al o ,.,,
.4 . .' " '
: ~paaMuos~Fr ~ ~ ~ ~ ~ ~ ~ o ~ ~ ~
-~UFU10~ ~ 1` ~r ~ ~ ~ a) ~ ~D O~ ~, . '
MOIlew a~Fua~
ue~q~os ~ ~ ~ ~ ~ o ~ ~ ~ ~ :
paaM~e~
uo~O~ O O O O O O O O O O O .,
aqal~nH
uaple~
p o d 3 l ~ D T S
:uld~ff ,~ ~ ~ ~ ~ ~ ~ ~ ~ ~ ~ - .
~o a~e~ r l ~ O ~ O O ~ O ~ O ~
,; '': .
: :~ 'M ald~x~
o punod~o~ ~ ~ ~ ~ .
X-4097A -122-
', '
1a~75696
~aqum~n;) ~ I~ o o ~ ~ o o r~
a~pas~n~ Molla~
ns
a~M n ~ o oo 1- ~ t~ I
ssel~ o o o o cr~ ~ o ~ o ~D
_ple~U~:ea ,~ ~ ~ ~ ~ ~
a~F~ oo ~ "~ ~ o
~0 PI~M 1~ r~ o o
u~n~loS u~e~g ~ o
o~
~PFS ~I~IDI~a ul ~o o o
~eal~aAI~A
sse~qe~
en~squle
~1 U10;~ 00 cn a~
paaMf~la o ~ o o o o r~
alll~ ~ o o o o o o r~ o In o
IF~xo~ ~ ~ ~ ~ ,~ " ~,
E-~ paaMuOSUlFr ~ ~ o o ~ ~ o ~ u~
~.11~ ~r ~ o o ~
-I;uFu~o~ ,t ,- ..
MolleW ~;: FUaA
ueaq~os N ~ ~ O r~
pa~
: uo~o~ o o o o ~ o o o o o o
isl~aqa~ nH ::
uap~eg
poda~ Fs ~.
ul dd~ ~ N N N `1 ~ N N Ll r~
,IO a~e~[ ~ o o o ~ o o ~ o
' N aldu~x ~[ ¦ O ~ ~ o o
~F punodulo;) I ~ ~ -I ~ ,1 u~ u, . ~ ~
X~4097A ~ -123- :
".
,'. . .
.
1~7~i696
~aqum~n~ o o ~ o o o In Lr~ r~ o u7
af~pas~nN ~0~ 5,
~aa~ l~fjns
I` i` Ner er 4~ `J Lr) ~
s s~ ~ oo~ o o o o a~ o o o
-p~e~ul~ ~ ,~
~ ~ ~ o~ D O ~ O
a~
~eo PIFM ~
~ ~ o
oS uFe~
~PF S ~ d ~r~g ~o o~ o a~ c~ o ~ o
~a~ A
~, .
ssel~q~ ~.
en}~squI~I
, :... .
:n ~ ou~ o er ~ o In l~ ~' '.
u~o~ .
pa~M~F a ,~
~ ~IITb~ ~s~ ~ ~
~1 IFe~X~
E~ paaMuOSUlFr ~r~ ~ oo o ~ ~ a) ~ 1~ ,.
..
.lolE,~r ~ ~ o ~o o cn ~) ~ N t`
_~uFu~o~
~olle~ ~Fual~ ~ :
ueaq~OS ~9 ~ o 1~ o x u~
p~33MEI~ :
UO:~ O;)o o o o o o o o o o o
'q~ )nH
; : u~3p:r~g
pod~ Fs
e~ 1
uldd~ NN Ir~ If) N If ~ N Ir~ N N N
~ 0 ~'~ NNl O O : O O O O O N O
: ~ o~ ~I duIex a ¦ ~~r U~Ln ~ 1- ~ ~ c~c~ a~ '
~F punod~o~
X-4097A ~ -124-
. . .
- - - ,
~L~75i~96
n~ o ~ ~ ~ ~ ~ o ~ r~ o o a~
a~pas~n~ ~olla~;
~aa~ ~e~ns
~a~M O ~ ~ ~ Q t~ 1 1' a~ a~ ~
sse~ r~ a~ o ~ o u~ oo o o o
pxe~u~ea
a~F~ ~:r o o o ~ ul ~ ~
~eo PIFM ~ .~ O ~D ~ ~ ~)
os uFe~3 o ~r ~ ~ o N
~PIS ~ F~a ~ o L~ In In O ~ 0~ 0 0
eal~aAIaA
s s e~qe~
a~len~squleq j ". .
u~o~ o o~ ~ ~ ~ ~r ~ ~ I~ O 0~ r~
paa~F a O u~ ~ N r~) ~ O 1~`) ~ ~
~allTw ~ O O co Ir) It~ ~ oo o o o
vIFe~xo~ ~ ~
~Ipaa~uoSulTr ~ r o 1~ o o o ~ -,
R~ UTU10~ o a~ ~ ~ O 1` ~
~olleW ~FUaA : ,;
ueaq~S o o N ~1 ~ O O ~) In O 1` 1
p~3a~e~
uo~ o o o o o o o o o o c:) ' o ''
aq~ nH :
u~pl~s : -
pod~ )FS . .
uldd~ ~ In ~
~o a~e~ ~ o ~ ~ ~r ~ ,i o ~ o ~i ;
N ~dulexa ¦ o a~ oo o q~ ,~ ~ ~ ~ u~
~o punodUlo;
X-4097A~ 125~
, '
~CIi7569~ii
Example 145
soil incor~orated test
In this test, the compounds of formula I were incor-
porated in the soil before the seeds were planted. Again, "
the method of Example 141 was followed in general. Various
compounds in this test were applied at a number of different
application rates, and the various compounds were tested
against various plant species.
X-4097A -126-
~ 7~ii6~6
nqa~ )o~ 1~ a~ o o ~ c~ ~ o
o o
h~~FU~ C~ O o
~ _,
o o o
~[~~11 H ~ ~ ,1
s se~ o o o o o o o o
-ple~u~e~ ~
3AIaA o o o o ~ o o o o
~)IIF~ IFe~xO,~ o o o o o o o o
a~p~3S~nN ~11~ u~ ~ o o co o oo o
sse~qel~ o o o o o o o o , ~ ,
~1~ o o o (n o o o o ~:' -
UFU~O~ : ~;
a~ ,~
R~a~enE~sc[lue~I o o o o o o o o
eplS ~T~l~F~a o o o cn o o o o
uo~o;) o ~ ~ co o o o o o
. ~, .
, P~ J;Ta ~ o o o o o o
aqalX;)n~
u~pleg o o o o o o o o
.,.. "... .
p~Muosul~r c~ o o o o c~ o o
CO ~D ~ '
~0. ....~.-
o o ~ ~ o, o o o o
:
o z ~ ,
~ a
: ~ ~ .-)
o~
X-4097A -127-
,
: . :
~7S~;96
~:rnqal ~ o; ) ", , o
~10 ~ ,~
~olle~ a:~FuaA o o
,,
~[~OT~ I H o o
sselfi o o o
-p~u~e~ ~ ~ ~ . .
eal~a~laA o o o ~ o
~ ~ ~ ~, . .
:~allFW IFe~xo,~ o o o o o o o i~ o o
a~pas~nM Molla~, ~ L~
sse~qe;~;) o O O o o o o cx~ o o
~1~ ~ o o o ~D 1~ 1`
,~ ,~
a~,~en~squ~ 3~ o o
~PFS ~ F~a o o o o o
,1 ,1 ~ ,1 ~1
UO~O;) o o ~ o o o o o o o
PaaM~Fd ~ ~ o o ~ a~ o~ o o
,1 ~ -I '
aDal~rDn~ O O
paaMuosulFr ~ ~
~ ~ ~ o o ~l o o o o o ~ o
o
a)
1 CO ~1 OD N
El' ~ ~ ~;r
O X . , .
~ ~ :,'
X- 4 0 9 7A -12 8- . :
~.
. ' '
., :
. , ~ . .. .. . . .
~6~75~
ExamE~ 146
surface-applied multiple-crop test
Representative compounds of formula I were tested
against a number of representative crop plants in a field
screen test wherein the test plots were artificially seeded
with weeds. Seeds of -the crops shown in the table below
were planted in rows in a medium-heavy midwestern soil. The
compounds identified below were applied in bands across the
rows of crop seeds, and were applied immediately afte:r the
seeds were planted. The bands were about 1 meter wide, so
that each test plot included a l-meter length of a row of
each crop shown below. The compounds were sprayed on the
surface of the soil in the form of an aqueous dispersion
similar to those described above in Example 139.
All of the test plots were overseeded with pigweed
and foxtail immediately before the plots were planted and
treated with the compounds. Untreated control plots were
provided for comparison with the treated plots.
A skilled plant scientist observed the plots 39
days ater they were planted and treated, and estimated the
percent control of the weeds and the percent injury to the
crops, The results are shown in the table below.
,
X-4097A -129- ~
'
~7569~
Q)
O O 1` 0 0 0 ~ O
O U) O
U~
~ .
.~
~) N O ~ n O cn ~ a~ I~ Il ) O 1
X ~ o~ ~ o a~ o o~
~1 .
a)
~ o ~ t~ o 1` ~ 1~ ~ o 1~ ~ r~ o
r~4 N ~ Ir) N Ifl r~ r--~ ~1 In N ~I N r-l
~1 .
l ~l ~ o o ~ NO ~ ~D ~) ao r~t
a~ u~
~l
.q ~?
0 ~
. E~ ~1
~ I~ r~ o t~ ~ I~ ~ O O O ~ I~ ~
0 ~ r) N ~)
J ~ 1~ I~ ,~ N ~ N 1`
-1 N 1~ N In ~ N ~ N U~ 11'1 ~.
r--I N ~ ~i N ql ~I N ~ ~i Nl ~ C~ .
~, :
q~ . : ,,,
O O . .
Z . ,.
r~:
~ 0
O X . ...
U 1:~1
X-4097A -130 - -
.
Exam~le 1 107S696
soil-incorporated multiple-cro~ test
The procedure of Example 146 was followed, except
that the compounds of formula I were incorporated with a
rotary tiller immediately after application. Crop and weed
seeds were planted immediately after application and in-
corporation of the compounds.
.
. .
.. . . .
.
~ ~; ' ' ,' ',` '. ,. '
~ ` :
,: :. .
.
~ X-4097A -I31
: ~: ::
~...................................................................... .
:' , . ... . ~.
7S6~
~ ~ ~ o ~ ~ i~ ~ o ~ o ~ o
O ~ In 1~ ~ ~ ~ ~ _I ~ ~ r~ ,
~a
:. ~ O .0 0 ~ O ~ ~ ~ O C~ I` er '
- .
.~ ~ '
~ ~ .
X ~ ~ I~ a~ o 1~ ' O
o ~1 ~ ~ a~ o ~ 1~ ~ o
h r~
.
1~ r~ 1~ o o t~ o ~ o
~1 ~r ao. o ~ oo o o ~ u~
O
.,1 u`, ~ ~ O O o ~ r~ o o 1` r~
, . ~1 O 1
~ CQ
a~ u, :
: ~ . .,
o r~ ~ ~ o r~ o ~ t~
~ ~.
~ o o o ~ o ~ o o o o o ~
~ ,, ~
:
.
d ~ ~1 If) ~I N N U) _I ~ N It) --I ~1 :
~ O ~ o ~i ~ o ~ ~ 1 o o
O O
Z
X-4097A `132- :
: ' :
: ~ , ' '. : '
, , , . . . : .:
.: : . : . ,, . .. .: : : ,
.
. ~ ., ~ .: . '
~75~;96 ~
I` o o r~ o
O N (~
U~
a~
3 O O O l` CO
~--/
P~
.~
o o ~r oo co
X ~D ~ ~ a~
O
I` ~ O
(I)
O C~ ~ I` U~
.,1 ,S: ' . .
o ~ ~ r` o
1:~ ~-I
O O
~.) U~
-'I ` .
O ~
~1 ~ O O O ~)
. ~
E~ ~1 - .'
~ :,
$ O ~ O O O
O
ta : ~:
~: ~ ~
In ~ ~ In
~ .
R~ ~ ~ o o ~1 ~ o
'.
': - ~ ..
~
O Z ~'
(U ':
~ ~-1 Ot~ ~1 " '
O ~ ~
O X '
~` 4097~ -133- ~ ~
~7~6
Example 148
. _
perennial weed test
.
The compound of Example 1 was tested against
typical perennial weeds. The compound was formulated
according to the procedure of Example 138. Applications of
the formulated compound were made to plastic pots of green-
house soil which had been planted with bindweed, bermuda-
grass, johnsongrass and quackgrass. Bindweed root stocks
and johnsongrass and quackgrass rhizomes were obtained from
field-growing plants, and bermudagrass stolons were rooted
from greenhouse-grown bermudagrass flats.
The compound, in its formulated form, was sprayed
evenly over the pots immediately after the weeds were
planted, and was lightly watered into the soil~ The pots
were individually fertilized a few days after treatment.
The pots were stored in the greenhouse, and the
plants were observed five weeks after application of the
compound. Weed control was rated on the 0-10 scale.
Appln.
Rate Bind- Bermuda- Johnson- Quack-
kg./ha. weed grass grass grass
0.28 10 5 1 8
0.S6 10 7 3 10
1.1 10 7 5 9
2.2 10 8 5 g -~
The same compound was also tested against the ~ame
weeds in a postemergence test, wherein the weeds were al-
lowed to grow for 30-60 days after planting before the
compound was applied. Before application of the compound,
the plants were trimmed back to a height of 4-B inches, and
' ' '
X-4097A -134-
~75696
,
the bindweed runners were trimmed back to the edge of the
pot. The plants were observed four weeks after treatment.
The results were as follows.
Appln.
Rate Bind- Bermuda- Johnson- Quack-
kg./ha. weed grass gras grass
0028 8 8 8 5
0.56 8 8 8 10
1.1 ~ 8 8 10
2.2 8 7 8 10
Example 149
perennial weed tests
.. .. _ .
In this typical experiment, the weeds and con-
ditions were similar to those of Example 148. A number of
exemplary compounds of formula I were used. The weeds w~re
observed about four weeks after application of the com-
pounds. The preemergence results were as follows.
X-4097~ -135-
.
1~75696
Compound
of Appln.
Example Rate Bind- Bermuda- Johnson- Quack-
No. ka./ha. weed grass ~rass grass_
_ _ _ _ _ _
1 1.1 10 9.8 10 10
0.56 10 9.8 10 10
0.28 10 8 10 10
0.14 10 8 9.5 10
51 1.1 10 9.5 10 10
0.56 10 9 10 10
0.28 10 5 7 ~
0.14 ~0 4 7
12 1.1 10 9.5 9.5 10
0.56 10 8 9 10
0.28 10 8 8 8
0.14 10 6 8
14 1.1 10 9.5 10 10
0.56 10 9 10 10
0.28 10 9 7 9
0.14 10 7 7 7
20 57 1.1 10 9.5 10 10
0.56 10 9 9.5 10
0.28 10 7 10 9
0.14 10 5 7 7
The results of the postemergence experiments
were as follow~
': ,
X-4097A -136-
~ '
107S69~ `
, .
Compound
of Appln.
Example Rate Bind- Bermuda- Johnson- Quack-
No. k~./ha. weed grass arass grass
.l 9.5 9O5
0.56 9 9.5 8 9
0.28 8 g.s
0.14 3 9
,, ,
51 1.1 9 9
0.56 9 8 7 9
0.28 7 5
o 0.14 5 4
2 1.1 9 9
0.56 9.5 9 8 7
0.28 ~ 5
0.14 7 4
4 1.1 9 9
0.56 9.8 9 8 9
0.28 8 8
b.14 7
57 l.l 9 9
0.56 9.5 9 7 8
0.28 5 6
0.14 4 3
EXample 150
-
mesquite test
Typ1cal compounds of formula I were tested against
mesquite trees growing in the greenhouse~ The trees were
transplanted,~when 5-12 inches tall, into l-gallon metal
::~ pots. After~the trees had begun to grow vigorously in the
: ~ ~pots, the compounds were applied as a soil drench. T~e
~compounds were formulated for application by dissolving them
X-4097A : -137-
:
: . . ` ..
107569G
in acetone:ethanol as described in Example 138, and dis-
persing the proper amount of the solution in 25 ml. of water
for application to each pot. The mesquite trees were
observed approximately 90 days after application of the
compounds, and control was rated on the 0-10 scale.
Compound
of Appln.
Example Rate
No. kg./ha.Ratings
34 1.1 6
2.2 6
4,5 7.5
37 1.1 7
2.2 4
4.5 8.5
1 1.1 9.8
2.2 9.9
4.5 9-9
47 1.1 9
2.2 9.5
4.5 9.9
48 1.1 10
2.2 9.9
4.5 10
51 1.1 0
2.2 4
4.5 7
6 1.1 10
2.2 9,5 ~;
4.5 9.9
' ' :
X-4097A -138-
.. . : .
1C1756~6
. ,
Compound
ofAppln.
Example Rate
No._kg./ha. ~atings
7 1.1 2
2.2 7.5
4.5 4
8 1.1 6
2.2 7
4.5 9.9
12 1.1 3
2.2 9
4.5 6
13 1.1 10
2.2 10
4.5 lQ
14 1.1 10
2.2 10
4.5 10
57 1.1 o
2.2 0
4-5 4
Example 151
grapefruit test
The compound of Example 1 was tested in a
grapefruit grove in a tropical climate. The soil was sandy
.
~ and the trees were grown with sprinkler irrigation in bedded
;~ ~ culture. The trees were approximately two years old when
the oompound was applied.
The compound was formulated according to the
method of ~xample 138, and was applied as a surface spray
. ~
to a 1 meter square plot around the base o~ each tree.
X-4097A -139-
, : ':
.; ' :'
11~756~6
Crop injury to the trees was rated on the 0-10
scale about 14 weeks after application of the compounds,
with the following results.
Rate
kg./
ha. 0~14 Or21 0~28 0~42 0~56 1~1 2~2 4~5
0.0 0.0 0.0 0.0 0.0 0.7 0.0 0.0
Weed control was also observed about 14 weeks
after application of the compound. The following results
were observed, expressed as percent control based on the
weed population of untreated control plots.
,'
.:: ...
., .::
X-4097A -140-
: . .:
~; ~
~7569~
Q)
0
~: .C
~ I~I`oooooo
r~,~ O) tJ~ O O O O O O
1~ t~ r-l r~ r~ r~
~,~
Z . ~.
tt)
~a ~
s~ r~ ~ ~ .~ O O U O O
o ~ ~ U~ ~O O O .,~ .~ O
,~ ~ ,~
I ~
~n
o .,
~-r~ s~ ~
r~ ~ ~ O O O O O O O O
Q)-,~ O o o o o o o o
~ ~ h ,~ ,-1 ,1 ,~,~ ,~ ,-1 ,~
C)W Q1
a) a)
a) tr) O O 0 0 0 0 o
Q~ ~ tx) o o t~ o o o o
~I 'd ,~
~C)
U~ . .
r,l
0
~ . .,
0 O Ot~ t~ t1D t'~ O tX~ '
~a ~ tr, ~
s~ 1.'
~0
,~ . .. .
0
t~ O o tr~ o 1~ o o t.
~ ,~ o~
~4 ::
,
. . ~ .
.
S ~ tx) t,~
,-1 Q~ ~ r-l ~ t~ t~
Q.~ .
~P~,Yi o O ~ ~ t~
'
X-4037A -141-
,
: '
.
,
,
~L~7~ ;96
Exam le 152
purple nutsQdge control in cotton tests
The compound of Example l was tested in field-
growing cotton infested with purple nutsedge. The cotton
was grown in a clay soil in flat cul1ure, with no irriga-
tion, in a sub-tropical climate. The compound was applied
as a water-dispersed 80~ we~table powder, and was incor-
porated into the soil immediately before the cotton was
planted. Crop injury and weed con~rol observations were
made, in percent injury or control, approximately eight
weeks after the compound was applied. The results were as
~ollows.
Appln. Bristly Purple Red
Rate Crop Starbur Nutsedge Tassellower
kg.~ha. Injury Control Control Control
.
0.56 0 27 20 33
0.84 0 60 67 80
l.l 0 68 73 90
1.7 0 90 90 lO0
2.2 0 99 99 lO0
3.4 o 99 99 ~o
Example 153
weed control in coffee tests
. . . _ _ ,
The compound of Example l was also applied to j -
e~tablished coffee in experiments much like those of the
example immediately above, except that the compound was
surface applied. Application of the compound at rates
up to 2 kg./ha. showed no injury to the coffee when the
crop was observed approximately six weeks and approximately
four months after application of the compound. Excellent
: '":
X-4097A -142-
~:- ,,
~7~69~ii
control of annual grasses, annual broadleavesl Paraguay
starbur, bristly starbur, hairy beygarticks, southern
sandbur, and purple nutsedge was observed in the experiment.
The outstanding broad-spectrum activity of the
compounds of formula I is clearly illustrated by the
above examples. The examples point up the efficacy of the
compounds against annual grasses, the relatively easily-
controlled broadleaves such as pigweed, and the more dif-
ficult to kill broadleaves such as the nightshades, ragweed
and sicklepod. Further, the compounds control such peren-
nial weeds as johnsongrass, quackgrass, bindweed, bermuda-
grass and nutsedge, which are very difficult to control.
The compounds also control algae and aquatic weeds, such as
coontail, hydrilla and the like. Still further, the com-
pounds kill such woody plants as mesquite, which is an
economically harmful weed in arid climates. Thus, plant
scientists will recognize that the compounds can be used to
control undesirable woody plants where such plants are not
wanted. Plant scientists will recognize that the exempli-
~ied activity of the compounds shows that the compounds areeffective against all types of weeds.
A preferred embodiment of the herbicidal method,
however, is the use of the method to selectively kill
herbaceous weeds.
Most unusually, the compounds of formula I are
herbicidally effective when applied both preemergence and
postemergence. Thus, they can be applied to the soil to
kill weeds by soil contact when the weed seeds are ger-
minating and emerging, and can also be used to kill emerged
weeds by dlrect contact with the exposed portions of the
X-4097A -143-
1~75~i96
weed. When the compounds are applied preemergence, the
weeds are killed either during germination or shortly after
emergence.
The compounds are effectively brought into contact
with aquatic weeds by either suspending or dissolving the
compound in the water in which the weeds grow, or by
applying the compound to the sub-aqueous soil in which
the weeds are rooted.
Because of the outstanding efficacy of the com-
pounds, a method of using the compounds for killing weedsis an important embodiment of the present invention. This
embodiment is a method of selectively killing weeds which
comprises contacting the weeds with an herbicidally-
effective amount of one of the compounds of formula I de-
scribed above. In the context of this invention, weed
seeds! which are contacted with the compounds through
preemergence applications of the compounds, are regarded as
weeds.
Preemergence applications of the compounds are
effective, as the examples show, whether the compounds are
applied to the surface of the soil or are incorporated in
the soil.
As the examples above illustrate, many of the
compcunds are acceptably safe to a number of crops, such as
peanuts, soybean, sorghum, wheat, rice and tree crops when
applied at proper rates and at appropriate times. It will
be noted that the compounds are particularly and notably
harmless to cotton in the exemplified experiments. Because
of the safety with which this crop may be treated with the
: . "' "
X-4097~ ~ -144-
"" , . . -,
:
: '
, , ,,. , ~ . . ~ - ;.. - . :
. , , . . ~ . . :
' - . . .' :: ' . ' :
~L0756~6
compounds, the use of the method to kill weeds in cotton
cropland is a preferred embodiment of the invention.
The compounds can also be used, at appropriate
application rates, for the total control of vegetation. Such
control is often desired, as for keeping cropland fallow
for a time, or on industrial property and xigh~s of-way.
The compounds' ability to control perennial weeds and woody
plants makes them particularly valuable total vegetation
control agents.
The method is notable for its ability selectively
to kill weeds. The term weeds is not used here in a re-
strictive sense, but is used to refer broadly to undesired ~-
and undesirable plants; hence, noxious vegetation. For
example, the method may be used in cotton cropland to kill
not only plants which are undesirable per se/ such as
johnsongrass and ragweed, but also volunteer crop plants
which are undesirable in a cotton field. It will be un-
derstood that the proper application rates must be used to
achieve selective control of weeds, as plant scientists are
well aware.
The proportion of the weed population which is
killed by an application of one of the compounds of formula
I depends upon the species of the weed and the identity and
amount of the compound applied. In many instances, of -
course, the whole populatlon is killed. In other instances,
part of the weeds are killed and part are injured, as some
of the examples above illustrate. It will be understood -~
that an application of one of the compounds is effective and
beneficial, even though only part of the weed population is
kllled and another part of the population is injuredO The
X-4097~ -l~S-
~:
... . .
- ., , : , ,
, , -
~L~75696
mere injury of a weed is beneficial, because the surrounding
crop, growing normally, shades out and kills the slow-
growing injured weed.
The best application rate of a given compound of
formula I for the control of a given weed varies, of
course, depending upon the method of compound application,
climate, 50il type, water and organic matter contents of
the soil and other factors known to those skilled in plant
science. It wil~ be found, however, that the optimum
application rate is in the range of from about 0.1 to about
20 kg./ha. in virtually every case. The optimum rates
will usually be found to be within the preferred range
of from about 0.1 to about 5 kg./ha.
The time when the compounds should be applied
to the soil or the weeds is widely variable, since the com- - -
pounds are effective both preemergence and postemergence~
At least some control of weeds will result from application
of the compounds at any time when weeds are growing or ger-
minating. They may also be applied to the soil during a
dormant season to kill weeds germinating during the fol-
lowing warm season.
When the compounds are used for weed control in an
annual crop, it is usually best to apply a preemergence
application of the compound to the soil at the time the
crop is being planted. If the compound is to be soil in-
corporated, it will usually be applied and incorporated
immedlately before planting. If it is to be surface applied,
it is usually simplest to apply the compound immediately
af~er planting.
X-4097A -146- -
., . ~ ~ , . . . .. .
~L~7~696
The compounds are applied to the soil or to
emerged weeds in the manners usual in agriculture. They may
be applied to the soil in the form of either water-dis~ersed
or granular formulations, the preparation of which will be
discussed below. Usually, water-dispersed~formulations
will be used for the application of the compounds to
emerged weeds. The formulations are applied with any of
the many types of sprayers and granular applicators which
are in wide use for the distribution of agricultural chemicals
over soil or standing vegetation. ~hen a compound is to be
soil-incorporated, any of the usual soil incorporation equip-
ment, such as the disc harrow, the power-dxiven rotary hoe
and the like, are effective.
The compounds are normally applied in the form of
the herbicidal compositions which are an important embodi- ;
ment of the invention. An herbicidal composition of this
invention comprises a compound of formula I and an inert
carrier. Tn general r the compositions are formulated in the
manners usual in agricultural chemistry, and are novel only
because of the vital presence of the novel herbicidal
compound.
Very often, the compounds are formulated as con-
centrated compositions which are applied either to the soil
or the foliage in the form of water dispersions or emulsions
containing in the range of from about 0.1 percent to about S
percent of the compound. Water-dispersible or emulsifîable
compositions are either solids usually known as wettable
powders, or liquids usually known as emulsifiable concen-
trates. These concentrated compositions are used in the
range;
X-4097A -147-
~ .
'
: . . , - . : . .. ~ .. . . .. ., . . , . ,:
. . . . . . . ..
~S6~6
%_by wei ht
compound of formula I 10-80
surfactant 3-10
inert carrier 87-10
Wettable powders comprise an intimate, finely-
divided mixture of the compound, an inert carrier and sur-
factants. The concentration of the compound is usually from
- about 10 percent to about 90 percent. The inert carrier is
usually chosen from among the attapulgite clays, the kaolin
clays, the montmorillonite clays, the diatomaceous earths
or the purified silicates. Effective surfactants, comprising
from about 0.5 percent to about 10 percent of the wettable
powder, are found among the sulfonated lignins, the con-
densed naphthalenesulfonates, the naphthalenesulfonates, the
alkylbenzenesulfonates, the alkyl sulfates and nonionic sur-
factants such as ethylene oxide adducts of phenol.
Typical emulsifiable concentrates of the com-
pounds of formula I comprise a convenient concentration of
the compound, such as from about 100 to about 500 g. per
liter of liquidr dissolved in an inert carrier which is a
mixture of water-immiscible solvent and emulsiiers. Useful
organic solvents include the aromatics, especially the
xylenes, and the petroleum fractions, especially the
high-boiling naphthalenic and olefinic portions of petroleum.
Many other organic solvents may also be used such as the
terpenic solvents, and the complex alcohols such as 2-ethoxy-
ethanol. Suitable emulsifiers for emulsifiable concentrates
are chosen from the same types of surfactants used fox
wet~able powders,
When a co~pound is to be applied to the soil, as
X~4097A 148-
..
.. ' .'
~7~696
for a preemergence application of the compound, it is con-
venient to use a granular formulation. Such a formulation
typically comprises the compound dispersed on a granular
inert carrier such as coarsely ground clay. The particle
- si~e of granules usually ranges from about 0.1 to about 3
mm. The usual formulation process for granules comprises
dissolving the compound in an inexpensive solvent and -
applying the solution to the carrier in an appropriate
solids mixer. Granular compositions are usually in fol-
lowing range:
% by weight
compound of formula I 1-10
surfactant 0-2
inert carrier 99-88
Somewhat less economically, the compound may be
dispersed in a dough composed of damp clay or other inert
carrier, which is then dried and coarsely ground to produce ;-;
the desired granular product.
:: : .:
.
X-4097A -149-
.
.
:
:.
