Note: Descriptions are shown in the official language in which they were submitted.
1~)6'79~
HERBICIDAL 1,4-DIPHENYL-3-PYRAZOLIN-5-ONES
This invention belongs to the field of agricul-
tural chemistry, and provides new herbicidal compounds to
the art. The growth of weeds, which are often defined as
plants growing where they are not wanted, has well-known
deleterious effects on crops which are infested with such
plants. Vnwanted plants growing in cropland, as well as in
~allow land, consume soil nutrients and water, and compete
with crop plants for sunlight. Thus, weed plants constitute
a drain on the soil and cause measurable losses in the yield
of crops.
The compounds of formula I below are new to organic
chemistry. Some compounds which have a relationship to the
present invention, however, are known in the herbicidal art.
Earlier workers have found herbicides among the pyridazinones,
for example, U.S. Patent 3,644,355. Some pyrimidinone
herbicides have also been disclosed in the agricultural
chemical art, such as the 6-alkyl-2,5~dihalo-3-phenyl-4-
pyrimidinones of U.S. Patent 3,823,135.
Some diphenyl-5-pyrazolinones have been disclosed,
for example, the 3-methyl-1,4-diphenyl compound of Beckh,
Ber. 31, 3164 (1898) and the 2-~lethyl-1,3-diphenyl compound
o Knorr et al., Ber. 20, 2549 (1887). A pharmaceutical
pyrazolinone is 2,3-dimethyl-1-phenyl--3-pyrazolin-5-one,
called antipyrlne, which was formerly used as an analgesic.
Merck Index,~93 (8th ed. 1968).
This invention provides to the agricultural -
.:
~chemical art~new compounds of the general formula
~ ;
.: .
~ X-4223A -2-
i:: . :
~ .
7907
wherein
R is Cl-C3 alkyl;
Rl and R2 independently are hydrogen, chloro, fluoro,
bromo, methyl or trifluoromethyl, provided that Rl and R2 do
not simultaneously represent hydrogen; and
provided that Rl may not be bromo or chloro in the 4-posi-
tion.
The compounds of formula (I) are prepared by
reacting a compound of the general formula
R~ 1l 1 '
\ c =~ H \ ~ (II;
wherein Rl and R2 are defined as before, with an alkylating
agent in the presence of a base. ;~
Suitable alkylating agents and bases are alkyl
halides, such as an alkyl iodide in the presence of a strong
inorganic base, or a dialkyl sulfate under strong basic
~ ~ conditions. I'he most convenient reaction temperature for
;; the alkylation is the reflux temperature of the reaction
~mixture. Alkylations of this typè are frequently preformed
and are common in the chemical literature.
In formula (I), the term Cl-C3 alkyl refers to
methyl, ethyl, or propyl.
~ X-4223A -3-
: :
: ~ , . '.
:: :
: . ! . . :
~0~ 7
Formula (I) above is believed to describe the
invention clearly. In order to assure that agricultural
chemists understand the invention, however, the following
exemplary compounds are presented. It will be understood
that the compounds below do not bound the invention, but are
merely typical of it.
4-(3-bromophenyl)-2-methyl-1-phenyl-3-pyrazolin-
5-one
1-(3-chlorophenyl)-2-ethyl-4-(3-fluorophenyl)-
3-pyrazolin-5-one
4-(3-chlorophenyl)-1-(2-fluorophenyl)-2-propyl-
- 3-pyrazolin-5-one
1,4-bis(3-bromophenyl)-2-methyl-3-pyrazolin-
5-one
2-propyl-1,4-bis(m-tolyl)-3-pyrazolin-5-one
4-(3-chlorophenyl)-2-methyl-1-(a,a,a-trifluoro-
_-tolyl)-3-pyrazolin-5-one
2-ethyl-1-phenyl-4-(m-tolyl)-3-pyrazolin-5-one
1-(3-chlorophenyl)-2-methyl-4-(m-tolyl) 3-pyra-
zolin-5-one
1-(2-bromophenyl)-2-propyl-4-(a,a,a-trifluoro-m- ; -
tolyl)-3-pyrazolin-5-one
4-(3-chlorophenyl)-2-methyl-1-(_-tolyl)-3
pyrazolin-5-one
4-(3-bromophenyl)-1-(2-chlorophenyl)-2-methyl-~;
3-pyrazolin-5-one
2-ethyl-1,4-bis(a,a,a-trifluoro-m-tolyl)-3-
pyrazolin-5-one
1-(3-fluorophenyl)-2-methyl-4-(a,a,a-trifluoro-
m-tolyl)-3-pyrazolin-5-one
X-4223~ -4- `
~-' '
;..~ ,.... ... .
~'7~
2-ethyl-l-(2-fluorophenyl)-4-(3-fluorophenyl)-
3-pyrazolin-5-one
2-ethyl-l-(3-fluorophenyl)-4-(m-tolyl)-3-pyrazolin-
5-one
4-(3-bromophenyl)-l-(4-fluorophenyl)-2-propyl-3-
pyrazolin-5-one
l-(2-bromophenyl)-4-(3-fluorophenyl)-2-propyl-
3-pyrazolin-5-one
l-(3-bromophenyl)-2-methyl-4 (m-tolyl)-3-pyrazolin-
5-one
2-methyl-4-(m-tolyl)-l-(a,a,-trifluoro-o-tolyl)-
3-pyrazolin-5-one :
4-(3-fluorophenyl)-2-methyl-l-.(a,a,a-trifluoro-
m-tolyl)-3-pyrazolin-5-one
The preferred compounds of formula (I) are those
wherein R is Cl-C2 alkyl;
R is hydrogen, chloro, or fluoro; and provided
that Rl may not be chloro in the 4-pos1tion;
R is trifluoromethyl.
Such preferred compounds are more particularly .
identified as the following: ..
.
2-methyl-l-phenyl-4-(a,a,a-trifluoro-m-tolyl)-3-pyrazolin-
~ ~5-one, 2-ethy1-1-phenyl-4-(a,a,a-trifluoro-m-tolyl)-3-
; pyrazolin-5-one, 2-ethyl-1-(4-fluorophenyl)-4- (a,a,a- ~-
trifluoro-m-tolyl)-3-pyrazo11n-5-one, 2-ethyl-l-(3-chloro-
phenyl)-4-(a,a~,a-trifluoro-m-tolyl)-3-pyrazolin-5-one,
:~ 2-methyl-l-(3-chlorophenyl)-4-(,a,~-trifluoro-m-tolyl)-
3-pyrazolin-5-one, 2-methy1-1-(2-ah1Oropheny1)-4-(a,,a-
trifluoro- -tolyl)-3-pyrazolin-5-one, l-(3-bromophenyl)-
30 : : ~
:
~;: X-4223A : -5- :.
., ~
,
~:3679()7
2-ethyl-4-(a,a,a-trifluoro-m-tolyl)-3-pyrazolin-5-one,
1,4-bis~3-chlorophenyl)-2-ethyl-3-pyrazolin-5-one, and 2-
methyl-l-(4-fluorophenyl)-4-(a,a,a-trifluoro-m-tolyl)-3-
pyrazolin-5-one.
The starting materials for the compounds of
f~rmula (II) are made most advantageously by a 2-step process.
First, a methyl or ethyl ester of phenylacetic acid, bearing
the R2 substituent on the phenyl ring, is reacted with
di(Alk)formamide di(Alk) acetal neat or in dimethylformamide
to produce an intermediate substituted ester of atropic acid
of the formula (III) below.
R~\ O
C COAIk
\~__ / 11 :
(III) HC-- N(Alk)
': '
The term Alk refers to methyl or ethyl. The reaction is ~ ~ -
carried out at temperatures from about 80 to about 140C. in -~
: . .
a flask open to the atmosphere.
The intermedlate III is then reacted with a phenyl- -
.
hydrazine or a hydrohalide thereof, bearing the R1 sub-
stituent, if any, on its phenyl ring, to form the desired
starting material of formula (II). When a phenylhydraz1ne
in the free base form is used, the reaction is carried out
in an aprotic solvent. The aromatic solvents such as
benzene and toluene, the aliphatics such as hexane and
octane, and the halogenated solvents such as methylene
~chloride and chloroform~are appropriate solvents. Xylenes
~are the preferred solvents. The most convenient reaction
temperature lS the reflux temperature of the reaction
,
:
~ X-4223A ~ , -6-
:
,..
, ~, - , . . . ~ . . , ., , ~ . , -
79C~
mixture, but other temperatures from room temperature to
about 120Co can be used if convenient in a given instance.
When a phenylhydrazine hydrohalide is used, the
reaction can be carried ou-t in an aprotic solvent as de-
scribed above in the presence of a base. Tertiary organic
amines such as triethylamine, pyridine, triethanolamine and
the like, and inorganic bases such as potassium carbonate,
sodium bicarbonate, alkali metal hydroxides and the like are
satisfactory bases.
~ 10 Alternatively, reactions using phenylhydrazine
hydrohalides may be performed by first reacting the hydra-
zine with the intermediate (III) in a lower alkanol at the
reflux temperature of the mixture to exchange the di(Alk)-
amino group of (III) with the arylhydrazine molety. The
resulting intermediate may then be cyclized by heatlng in an
aprotic solvent such as xylene at temperatures from about
50 to about 120C~ Alternatively, the resulting inter-
mediate may be cyclized by heating in a lower alkanol at
reflux temperature with inorganic bases such as potassium
carbonate, alkali metal hydroxides, or alkali metal alkoxides.
All of the starting compounds used to prepare the
compounds of formula (III) are commonly known in the chemical
art and are readily obtainable.
A few typical preparative examples will be shown
to assure that organic chemists can obtain any desired
compound of formula (I). All of the products described
below were identifled by nuclear magnetic resonance analysis
and-elemental microanalysis.
'
X-~223~ ~7~
: :
~ ~ ,
~L06 ~
Example 1
A 10.9 g. portion of 3-trifluoromethylphenylacetic
acid, methyl ester, was combined with 11.9 g. of dimethyl-
formamide dimethyl acetal and the mixture was heated over-
night on the steam bath. In the morning, the reaction
mixture was taken up in methanol and poured over ice. The
aqueous mixture was filtered, and the solids were recrystal-
lized from aqueous ethanol to produce 4 g. of m-trifluoro-
methyl-~-(dimethylamino)atropic acid, methyl ester, m.p.
45-49C.
The ester prepared above was combined with 1.6 g.
of phenylhydrazine in 25 ml. of benzene and the mixture was
refluxed overnight. About 25 ml. o~ p-xylene was added and
the mixture was refluxed for 2 hours more. The reaction
mixture was then cooled, and the resulting solids were
separated by ~iltration and identified as 2.6 g. of l-phenyl- ~-
4- (a,a,a- trifluoro-m-tolyl)-3 pyrazolin-5-one.
A 1.5 g. portion of the pyrazolinone was dissolved
in 50 ml. of methanol, and 0.7 g. of methyl iodide and 0.7
g. of potassium carbonate were added. The mixture was
stirred at reflux temperature overnight. The mixture was
then poured over ice, and the aqueous mixture was filtered
to recover the product, which was recrystallized from ethyl
acetate-hexane. The product was 0.85 g. of 2-methyl~l-phenyI-
4-(a,a,a-trifluoro-m-tolyl)-3-pyrazolin~5-one, m.p. 153-155C.
Theoretical~ound
C64.15~64.17
H4.12 4.19
N8.80 8.77
X-4223A ~ -8-
~ , ' ' ' ,
1Clt:;79V7
Example 2
A 9 g. portion of 3-fluorophenylacetic acid,
methyl ester, was reacted with 6.5 g. of dimethylformamide
dimethyl acetal in 15 ml. of dimethylformamide at 120C. to
produce 11.2 g. of the corresponding m-fluoroatropic acid,
- methyl ester. The ester was reacted with 5.4 g. of phenyl-
hydrazine in 50 ml. of toluene at reflux temperature for 4
- hours. An equal volume of m-xylene was then added, and the
mixture was refluxed overnight. The mix~ure was then cooled
and decanted, and the solids were triturated with benzene
and filtered. The separated solids were slurried in hot
benzene-ethyl acetate, and filtered again. The solids were
then recrystallized from ethanol to produce 2.9 g. of 1-
phenyl-4-(3-fluorophenyl)-3-pyrazolin-5-one, m.p. 189C.
A 2.4 g. portion of the above pyrazolinone was
combined with 3.9 g. of methyl iodide and reacted as described
in Example 1 above. The product, after recrystallization
from-benzene-hexane, was 1.5 g. of 2-methyl-1-phenyl-4-t3-
fluorophenyl)-3-pyrazolin-5-one, m.p. 134C.
TheoreticalFound
C71.63% 71.35
H4.88 5.01
~ N10.44 10.17
Example 3
A 3 g. portion of the 2-unsubstituted pyrazolinone
of Example 1 was reacted with 10 ml. of propyl iodide to
produce 0.45 g. of 1-phenyl-2-propyl-4-(a,~,a-trifluoro-m-
tolyl)-3-pyrazolin-5-one, an oily liquid.
' ,' ',~ '.
X-4223A -9-
:
:. . :
~6'~07
Theoretical Found
C~5.89~ 65.64
H 4.95 5.09
N 8.09 7.97
Example _
A 2.5 g. portion of the 2-unsubstituted pyrazo-
linone of Example 1 was reacted with 1.2 g. of ethyl iodide.
The alkylated product was 1.2 g. of 2-ethyl-1-phenyl-4-
(a,a,a-trifluoro-m-toly1)-3-pyrazolin-5-one, m.p. 156-157~C.
TheoreticalFound
C65.06% 65.25
H4.55 4.65
N8.43 ~.40
A 17 g. portion of 3-chlorophenylacetic acid,
methyl ester, was combined with 12 g. of dimethylformamide
dimethyl acetal in lOO ml.~of dimethylformamide and the ~
mlxture was heated in an open flask at the boiling tem- ~ -
perature of the mixture for 6 hours. The hot reaction
~20~ mixture was then poured over ice~, and the aqueous mixture
was filtered. The solids were recrystallized from benzene-
hexane to produce~13 g. of the 3-chloroatropic acid, methyl
ester, m.p. 84-86C. ~
A~4.8 g. portion of the above intermediate was
reacted~wLth~2~.2 g. of phenylhydrazine to produce 3.5 g. of
l-phenyl-4-(3-~chlorophenyl)~-3-pyrazolin-5-one, m.p. 197-199C.
;A 2~g~. portion~o~f~the~above intermediate was
alkylated~w1th~2.7 g. of methyl~iodide~to~ produoe~l g. o~
2-methyl-1-phenyl-4-(3-chlorophenyl)-3-pyrazolin-5-one, m.p.
30 ~ 49~-~150C.~
X-42~23A~ -10-~ ;
Theoretioal Found
C ~7.4'~% 67.24%
H 4.60 4.38
N 9.84 9.80
Example 6
A 5.5 g. portion of the atropic ester of Example 1
was combined with 3.5 g. of 4-fluorophenylhydrazine hydro-
chloride and 2 g. of triethylamine in 50 ml. of benzene.
The mixture was stirred at reflux temperature for 5 hours,
after which about half of the benzene was allowed to evapo-
rate and an equivalent amount of m-xylene was added. The
mixture was then stirred at reflux overnight, and the
reabtion mixture was evaporated to dryness under vacuum.
The residue was partitioned between ethyl acetate and water,
.
and the organic layer was dried~over sodium sulfate and
..
evaporated to dryness. The residue was chromatographed on
silica gel with~ethyl acetate~as the eluant. The product-
contai~ning fractions~were~combined~and evaporated to dryness ~ -
to produce about 3.5 g. of crude product, which was recrystal-
llzed from methanoi to produce 2.7 g. of purified 1-(4-fluoro-
;~ ; phenyL?~-4-(a,a,a-trifluoro-m-tolyl)-3-pyrazolin-5-one, m.p.
171-173C.
~ ~ . . . :
Two g. of the above intermediate was alkylated
w~ith 2.7 g.~ o~ methyl iodide to produce 1.6 g. of 2-methyl-
(4-fluorophenyl)-4-(a,~,a-trifluoro-m-tol~yl)-3-pyrazolin-
5-one,~m.p. 165C.
Theoretical Found
C~ 60.72% 6~ 99% ~ ~
H~ ~ ;3.60 3.5~ . -
30~ N ~ 8.3~3 ~8.3Z ~ -
X-4223A ~
.
~L06~7~
Example 7
A 3.5 g. portion of the atropic ester of Example 1
was reacted with 2.3 g. of 3-chlorophenylhydra2ine hydro-
chloride in the presence of 1.3 g. of triethylamine in m-
xylene according to the scheme of Example 6. The product
was 2 g. of 1-(3-chlorophenyl)-4-(a,a,a-trifluoro-m-tolyl)-
3-pyrazolin-5-one, m.p. 182-184C.
A 1.65 g. portion of the above intermediate was
alkylated with 2 g. of methyl iodide to produce 1 g. of
2-methyl-1-(3-chlorophenyl)-4-(a,a,a trifluoro-m-tolyl)-
3-pyrazolin-5-one, m.p. 130-131C.
Theoretical Found
C 57.89% 58.13%
H 3.43 3.59
N 7.94 8.04
Example 8
A 2.2 g. portion of the atropic ester of Example 1
was reacted with 1.3 g. of m-tolylhydrazine hydrochloride in
the presence of triethylamine to produce 1.7 g. of l-(m-
20 tolyl)-4-(,a,a-trifluoro-m-tolyl)-3-pyrazolin-5-one, m.p. ~ -
158-159C.
A 1.6 g. portion of the above intermediate was
.
alkylated with 2 g. of methyl iodide to produce 1 g. of
2-methyl-1-(m-tolyl)-4-(a,a,a-trifluoro-m-tolyl) 3-pyrazolin-
5-one, m.p. 153-154C.
Theoretical Found
C 65006% 65.19%
H 4.55 4.32
N 8.43 8.33
X-4223A ~ ~-12-
:: .
~0~ ~ 9~7
Example 9
A 3.5 g. portion of the atropic ester of Example 1
was reacted with 2.7 g. of ,,a-trifluoro-m-tolylhydrazine
hydrochloride in the presence of triethylamine to produce
2.4 g. of 1,4-bis(a,a,a-trifluoro-m-tolyl)-3-pyrazolin-5-one,
m p. 207-208C~
A 1.8~ g. portion of the above pyrazolinone was
reacted with 2 g. of methyl iodide to produce 1.25 g. of
2-methyl-1,4-bis(a,a,a-trifluoro-m= tolyl)-3-pyrazolin-5-one,
m.p. 110-111C.
Theoretical Found
C 56 2~% 56.04% -
H . 2. 62 2.86
N 7.29 7.19
Example 10
A 2.7 g. portion of the atropic ester of Example 1
was reacted with 1.8 g. of 2-chlorophenylhydrazine hydro-
chloride in the presence of triethylamine to produce 1 g. of
1-(2-chlorophenyl)-4-(a,a,~-trifluoro-m-tolyl)-3-pyrazolin-
.
5-ona, m.p. 236C.
One g. of the above pyrazolinone was alkylated
.
with 1 g. of methyl iodide to produce 0.45 g. of 2-methyl- -
1-(2-chlorophenyl)-4- (a,a,a~trifluoro-m-tolyl)-3-pyrazolin-
5-one~, m.p. 175C.
Theoretical Found
~ ~ ~ C 57 ~7~ 57-3~%
: ~ H 3.40 3.51
.
~ N ~ 7.94 7.93
, . ~
: ~ .,
' .
~;-4223A -13-
. ~ ~ ....................... . . .
: ' ' , '
~lti'7~31Q7
Example 11
A 2.6 g. portion of 1-(3-chlorophenyl)-4-(a,a,~-
trifluoro-m-tolyl)-3-pyrazolin-5-one, prepared in Example 7,
was alkylated with ethyl iodide to produce 0.25 g. of 2-
ethyl-l-(3-chlorophenyl)-4-(a,a,a-trifluoro-m-tolyl)-3-
pyrazolin-5-one, an oily liquid.
Theoretical Found
C58.95~ 58.89~ -
H 3.85 3.61
N 7.64 7.52
Example 12
A 15 g. portion of the atropic ester of Example 1
was allowed to react with 10 g. of 3-fluorophenylhydrazine
hydrochloride in methanol at reflux temperature for about 2 -~
days. The solvent was evaporated and the residue parti- ~:
tioned between ethyl acetate and water. The organic layer
was separated and concentrated in vacuo to leave a residue. -
The residue was recrystallized from a mixture of ethyl
acetate and hexane to yield product having a melting point - :
of about 172C. and weighing 2.1 g. The product was iden- ;
tified as 1-(3-fluorophenyl)-4-(a,a,~-trifluoro-m-tolyl~-
3-pyrazolin-5-one.
The 2.1 g. of pyrazolinone prepared above was `i ~ -
placed in 40 ml. of ethanol together with 15 ml. of ethyl
lodide and~l g. of potassium carbonate and the mixture
refluxed for about 8 hours. The reaction product mixture
was concentrated ln vacuo~and the residue partitioned
between ethyl acetate and water. The ethyl acetate layer
was separated and dried, and concentrated in vacuo, and the
residue~chromatographed on a sillca gel column u~-ng~a
X-4223A ~ -14-
~, :
.
: : ~
6'79~
mixture of ethyl acetate and hexane in a ratio o~ 1:2. The
product which was isolated had a melting point of about
140-141C. and weighed 0.7 g. The product was identified as
2-ethyl-1-(3-fluorophenyl)-4-~a,a,a-trifluoro-m-tolyl)-3-
pyrazolin-5-one.
Theoretical Found
C 61.71% 61.72
H 4.00 4.06
N 8.00 8.00
Example 13
A 4 g. portion of 1,4-bis(a,a,a-trifluoro-m-
tolyl)-3-pyrazolin-5-one (from Example 9) was heated with 20
ml. of ethyl iodide, 3 g. of potassium carbonate, and 40
ml. of ethanol at reflux temperature for about 4 hours. The
reaction product mixture was concentrated ln vacuo and -
extracted with ethyl acetate. The extract was dried over
anhydrous magnesium sulfate, the drying agent filtered off
and the filtrate concentrated in vacuo. On standing over-
night the residue solidified and was recrystallized from a
mixture of hexane and benzene. The solid was chromato-
graphed on a silica gel column using a mixture of ethyl
acetate and hexane in the ratio of 1:2. The product from -
the column was~then recrystallized from a mixture of hexane
and benzene to yield product having. a melting point of about
110-111C., and identified as 2-ethyl-1,4-bis(a,a,a-trifluoro- -
m-tolyl3-3-pyrazolin-5-one.
Theoretical Found
C57.00% 56.63%
H 3.50 3.49
N 7.00 6.85
X-422~3A -15-
IL0~7~
Example 14
A 13.7 g. portion of the atropic ester of Example
l was allowed to react with 11.2 g. of 3-bromophenylhydrazine
hydrochloride in 100 ml. of methanol at reflux temperature
overnight. The solvent was evaporated, and the residue was
refluxed in 100 ml. of m-xylene and 5 g. of triethylamine
for about 16 hours. The reaction mixture was concentrated
in vacuo and the residue chromatographed on a silica gel
column using 1:1 ethyl acetate-hexane. There was obtained
7.5 g. of product, which was identified as 1-(3-bromophenyl)-
4-(a,a,a-trifluoro-m-tolyl)-3-pyrazolin-5-one.
A 7.5 g. portion of the above pyrazolinone was
combined with 4 g. of potassium carbonate and 15 ml. of
ethyl iodide in lO0 ml. of ethanol and heated in the same
manner as previously described for other similar compounds.
There was obtained 2.0 g. of product having a melting point
of about 106C., and identified as 1-(3-bromophenyl)-2-
ethyl-4-(a,a~a-trifluoro-m-tolyl)-3-pyrazolin-5-one.
~ Theoretical Found
C52.57~ 52.80
.:
N 6.81 6.98
Example 15
A 6 g. portion of 1-(4-fluorophenyl)-4-(a,~,a-
~trifluoro-m-tolyl)-3-pyrazolin-5-one (prepared in Example 6)
was mixed with 4 g. of potassium carbonate and 15 ml. of
ethyl iodide in lO0 ml. of ethanol and refluxed overnight.
There was isolated in the usual manner 1.8 g. of product
having a melting Poin~ f about 92C., and identified as
X-4223A -16-
.
.
~06 ~9 0!7
2-ethyl-1-(4-fluorophenyl)-4-(a,a,a-trifluoro-m-tolyl)-3-
pyrazolin-5-one.
Theoretical Found
; C61.72~ 61.87
4.03 ~.20
N 8.00 8.06
Example 16
A 12 g. portion of the 3-chloroatropic acid,
methyl ester (prepared in Example 5 above) was allowed to
react wlth 10 g. of 3-chlorophenylhydrazine hydrochloride in
100 ml. of methanol at reflux temperature overnight. There
was obtained 10 g. of product having a melting point of
about 173-174C., and identified as 1,4-bis(3-chlorophenyl)-3-
pyrazolin-5-one.
A mixture of 7 g. of the pyrazolinone prepared
above, 4 g. of potassium carbonate, and 15 ml. of ethyl
iodide in ethanol was refluxed overnight. There was i90-
lated, after recrystallization from ether, 3.0 g. of product
havlng a melting point of about 101C., and identified as
20 1,4-bis(3-chlorophenyl)-2-ethyl-3-pyrazolin-5-one.
Theoretlcal Found
C61.28~ 61.04%
H 4.24 4.21
N 8.4I 8.55
ExampIe 17
A mixture of 12 g. of the 3-chloroatropic acid,
methyl ester (prepared~in Exa~mple 5 above), 13 g. of m-
trifluoromethylphenylhydrazine hydrochloride and 100 ml. of
methanol was~reflux~ed overnight to yield 4.6 g. of prodùct
~. .
30 having a melting point of about 190-192C., and identified
X-4223A ~ -17-
. ~ . . .
.. ~ . ' :. .
~06'7~(~7
as 4-(3-chlorophenyl)-1-(a,a,a-trifluoro-m-tolyl)-3-
pyrazolin-5-one.
A mixture of 4.6 g. of the pyrazolinone prepared
above, 4 g. of potassium carbonate, 15 ml. of ethyl iodide
and 50 ml. of ethanol was refluxed overnight. The reaction
product mixture was worked up in the customary way to yield
1.8 g. of product having a melting point of about 113-114C.
and identified as 4-(3-chlorophenyl)-2-ethyl-1-(a,~,~-
trifluoro-m-tolyl)-3-pyrazolin-5-one.
Theoretical Found
C58.95~ 58.84%
H3.85 3.89
N7.64 7.63
Example 18
A 120 g. portion of phenylacetic acid, methyl
ester, was combined with 95 g. of dimethylformamide dimethyl
acetal in 200 ml. of dimethylformamide, and heated to gentle ~ ;
reflux for about four days, while adding, at intervals, 5 g.
portions of dimethylformamlde until a total of 140 g. addi-
tional had been added. At the end of the heating period,
the reaction m1xture was allowed to cool to room temperature
and was poured over crushed ice. The oily product which
separated eventually crystallized. The crystalline product
was washed with water, cooled in the refriyerator, filtered
off and air drled. The crude product was recrystallized
~from cyclohexane to yield product havlng a melting point of
about 58-60C., which was idèntified as ~-(dimethylamino)-
atropic acidj methyl~ester. ~ -
X-4223A ~ -18- ; ~
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......... .. .. . . .
IL ~!67 9 ( ~ 7
Theoretical Found
. _ _
C 70.22% 70.47
H 7.37 7.36
N 6.82 6.85
A mixture of 10.5 g. of the atropic acid, methyl
ester, 9.1 g. of 3-chlorophenylhydrazine hydrochloride, and
200 ml. of methanol was refluxed overnight. The reaction
product mixture was worked up in the usual manner to yield
11 g. of crude 1-(3-chlorophenyl)-4-phenyl-3-pyrazolin-
5-one. A sample recrystallized from methanol had a melting
point of about 211-212C.
A mixture of 4 g. of the above preparéd pyrazo-
linone, 20 ml. of ethyl iodide, 20 ml. of ethyl bromide,
3 g. of potassium carbonate, and 40 ml. of ethanol was
refluxed for about 4 hours. The reaction product mixture
was worked up to yieId 0.9 g. of an oil, which was iden-
tified as 1-(3-chlorophenyl)-2-ethyl-4-phenyl-3-pyrazolin-
5-one.
Theoretical Pound
C 68.34~ 68.15
H 5.06 4.89
N 9.38 9.29
Example 19
A mixture of 8.2 g. of the atropic acid, methyl
:
; e~ster, (prepared in Exampla 18), 8.5 g. of m-trifluoro-
methylphenylhydrazine hydrochloride, lOO ml. of benzene and
.
~ g.; of triethy~lamine~, was reflu~ed overnight and worked up -~
,,
to yield 6.5 g. of 4-pheny1-1-~(a,~,a-trifluoro-m-to1yl)-
3-pyrazolin-5-one having a melting point o~ about 210-213C. ~ ~;
30 ~
X-4223A~ -19-
.
: , :
:
~6'79V~
A mixture of 2.2 g. of the pyrazolinone prepared
above, 2 g. of potassium carbonate, 25 ml. of ethyl iodide
and 25 ml. of ethanol was re1uxed for about 3 hours. The
reaction mixture was worked up in the usual manner to yield
an oll whlch was identified by NMR spectrum as 2-ethyl-4-
phenyl-l-(a,a,~trifluoro-m-tolyl)-3-pyrazolin-5-one.
The compounds of formula (I) have been tested in
a number of herbicidal test systems to determine the range
of their herbicidal efflcacy. The results produced by the
compounds in the representative tests reported below are
exemplary of the activity of the compounds.
Compound application rates are expressed in kilo-
grams of the compound per hectare of land (kg./ha.) through-
out this document.
Blank spaces in the tables below indicate that the
compound was not tested agalnst the named species. In the
tests below, plants were rated on a 1-5 scale, on which 1
indicates normal plants and 5 indicates dead plants or no
emergence. The compounds are identified by their example
numbers.
Test 1
; broad spectrum greenhouse test
; Square~plastic pots were filled with a sandy
sterilized greenhoùse soil and were planted to seeds of
tomato, large crabgrass and pigweed. Each pot was indiv- ;
idually fertilized. ~ -
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-
X-4223A ~ ~ -20-
: . .
~06~9ff7
cations were sprayed on the soil the day after the seedswere planted.
Each test compound was dissolved in 1:1 acetone:
ethanol at the rate of 2 g. per 100 ml. The solution also
contained about 2 g. per 100 ml. of an anionic-nonionic
surfactant blend. One ml. of the solution was diluted to 4
ml. with deionized water, and 1-1/2 ml. of the resulting
solution was applied to each pot, resulting in an appli-
cation 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.
The table below reports results of testing typical
compounds of formula ~I).
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Te s t
multi-spec es greenhouse test
The test was conducted in general like the test
above. The seeds were planted in flat metal trays, rather
than in pots. The compounds were formulated according to
the procedure above, except that about 6 g./100 ml. of the
compound was dissolved in the surfactant-containing solvent,
and the organic solution was diluted with appropriate amounts
of water before application to the trays. The compounds
were applied at various rates which are indicated in the
table below and the results of testing against the species
-named below are as follows. Where more than one replicate
was run, the results were averaged.
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Test 3
resistant weed tests
_
Typical compounds were evaluated in a test system
which determined their ability to reduce the vigor of weeds
which are resistant to many herbicides. The compbunds were
formulated and dispersed, and the dispersions were applied,
as described in Test 1 above. The application rate was 9.0
kg /ha. in all Of the tests reported h~re.
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X-4223A : ~ -33
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The broad spectrum activity of the compounds of
formula (I) is illustrated ~y the above examples. The test
results point up the efficacy of the compounds against
annual grasses, the relatively easily-controlled broadleaves
such as pigweed, and the more resistant broadleaves such as
nightshades. Plant scientists will recognize that the
exemplified activity of the compounds shows that they are
broadly effective against unwanted herbaceous plants, which
will be referred to as weeds, for the sake of brevity.
As the above test results demonstrate, the com~
pounds are used to reduce the vigor of weeds by contacting
them with an herbicidally-effective amount of one of the
compounds. The term "reduce the vigor of" is used to refer
to both killing and injuring the weed which is contacted
with a compound. In some instances, as is clear from the
test results, the whole population of the contacted weed is
killed. In other instances, part of the weeds are killed
and part of them are injured, and in still other instances,
~none of the weeds are killed but are merely injured by
application of the compound. It will be understood that
reducing the vigor of the weed population by injuring part
of them is beneficial, even though part of the population
survives application of the compound. The weeds, the vigor
of which has been reduced/ are unusually susceptible to the
stresses which normally afflict plants, such as disease,
drought, lack of nutrients and so forth.
Thusj the treated weeds are likely to expire due
to stress of the environment, even though they survive
application of the compound. Further, if the treated weeds
are growing in cropland, the crop, as it grows normally,
X-4223A -34-
.: .
~06'790'~
tends to shade out the treated weeds of reduced vigor.
Therefore, the crop has a great advantage over the treated
- weeds in the competition for nutrients and sunlight. Still
further, when the treated weeds are growing in fallow land,
or industrial property which is desired to be bare, the
reduction in their vigor necessarily tends to minimize the
treated weeds' consumption of water and nutrients, and also
minimizes the fire ha~ard and nuisance which the weeds
present.
The compounds are herbicidally effective when
applied both preemergence and postemergence. Thus, they can
be used both by direct contact of the compounds with emerged
weeds, and by applying the compounds to the soil, where they
come in~to contact with germinating and emerging weeds.
Preemergence appllcation of the compounds, wherein the ger-
minating and emerging weeds are contacted with the compound
through soil application, is preferred.
Accordingly, an important embodiment of this
invention is a method of reduclng the vigor of weeds which -
comprises contacting the weeds with an herbicidally-effective
.
amount of a compound of formula ~I). The term herbicidally-
effective amount refers to an amount which will reduce the
vigor of the treated weed. In the context of this invention,
weed seeds, which are contacted with the compounds by appli-
cation of the compounds to the soil, are regarded as weeds.
Amounts of herbicides are measured in terms of the
weight of herbicide applied per unit area, usually called
the application rate. The best application rate of a given
,
compound of formula (I) for the-control of a given weed
;~ 30 ~ varies, of course, depending upon the climate, soil texture,
X-4223A ~ -35-
~ .
lQti~7~0~
water and organic matter contents of the soil and other
factors known to those skilled in plant science. It will
be ~ound, however, that the optimum application rate is usual-
ly in the range from about 0.5 to about 20 kg./ha.
It is not implied, of course, that all compounds of
formula (I~ are effective against all weeds at all rates.
Some compounds are more effective against some types of weeds,
other compounds are more effective against other types.
All of the compounds, however, are effective against at least
some weeds. It is within the ordinary skill of a plant sci-
entist to ascertain the weeds which are most advantageously
controlled with the various compounds, and the best applica-
tion rate for the particular use.
The compounds are applied to the soil or to emerged
weeds in the manners usual in agriculture. It is best to apply
the compounds in the form of the herbicidal compositions which
are important embodiments of the pxesent invention. They may
be applied to the soil in the form of ~ither water-dispersed
or granular compositions, t~e preparation of which will be dis-
cussed below. Vsually, water-dispersed compositions will be
; used for the application of the compounds to emerged weeds.
The compositions are applied with any o the many types of
sprayer~s and granular applicators which are in wide use for
the distribution of agricultural chemi~als over soil or stand-
ing vegetation. In general, the compositions are formulated
in the manners usual in~agr~lcultural chemistry.
Very often, the compounds are formulated as concen-
~rated compositions which are appiied either to the soil orthe foliage in the form;of water dispersions or emulsions
30 ~
36-
.
".,
~ , .. .
~06t7907
containing in the range of from about 0.1 percent to about 5
percent of the compound. Water-dispersible or emulsifiable
compositions are either solids usually known as wettable
powders, or liquids usually known as emulsifiable concen-
trates. Wettable powders compr:ise an intimate, finely-
divided mixture of the compound, an inert carrier, and
surfactants. 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 montmorillonite clays, the kaolin clays, the diato-
maceous earths and 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 condensed naphthalenesulfonates, the naphthalene-
sulfonates, the alkylbenzenesulfonates, the alkyl sulfates
and nonionic surfactants such as ethylene oxide adducts of ;~
phenol.
:
Typical emulsifiable concentrates of the new
.
compounds comprise a convenient concentration of the com-
- 20 pound, such as fxom ahout 100 to about 500 g. per llter of
liquid, dissolved ln an inert carrier which is a mixture of
water-immiscible solvent and emulsifiers. Useful organic
solvents include the aromaticsj especially the xylenesj and
~ ~ the petroleum fractions, especially the high-boiling naph-
; ~ ~thalenlc 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-ethoxyethanol.
Suitable emulsifiers for emulsifiable concentrates are
;chosen from the~same types~of surfactants used for wettable
powders.
X-4223A~ -37
,:
~0~7~13'7
When a compound is to be applied to the soil, as
for a preemergence application of the compound, it is con-
venient to use a granular formulation. Such a fonnulation
typically comprises the compound dispersed on a granular
inert carrier such as coarsely ground clay. The particle
size of granules usually ranges from about 0.1 to about 3
mm. Th~ 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. 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.
It has become custo~ary in agricultural chemistry
to apply two or even more agricultural chemicals simultaneously
in order to control weeds of many different types, or weeds
and other pests, with a single application of chemicals.
.
The compounds of formula ~I) lend themselves well to com-
bination with other~agricultural chemicals and may usefully
be combined with insecticides, fungicides, nematicides and
other herbicides as may b desirable.
. ~ , :
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X-4233A -3B-
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