Note: Descriptions are shown in the official language in which they were submitted.
H~RBICIDALLY ACTIVE 3-ISOXAZOLYL-2-
IMIDAZOLIDINONE DERIVATIVES
Field Of The Invention
This invention relates to certain 3-isoxazolyl-2-imidazolidinone
derivatives, namely 3-[5- or 3-substituted-3- or -5-isoxazolyl]-1-,4- or 5-
substituted-2-imidazolidinones and the use thereof for preemergence or
postemergence control of noxious plants, i.e., weeds.
~ Description Of The Invention
This invention provides herbicidally active 3-[5- or 3-substituted-
3- or 5-isoxazolyl]-1,-4- or 5-substituted-2-imidazolidinones represented
by the Formula I:
I.
o
A--N N--
~<
R R3
wherein A is
H H
R ~ _ or R 4
O N N - O
where
R is an alkyl of up to six carbon atoms, an alkenyl
of up to five carbon atoms, an alkynyl of up to
five carbon atoms, a cycloalkyl selected from the
group consisting of cyclopropyl, cyclobutyl,
cyclopentyl, and cyclohexyl, a haloalkyl of up to
9iX carbon atoms, -R4-o-R5 or R4-S-R5, where R4 is
an alkylene of up to six carbon atoms and R5 is an
alkyl of up to six carbon atoms,
Z ~ R4 , or Z ~ 0 - R4
where Z is nitro (-N02), chloro (-Cl), bromo (-Br),
fluoro (-F), or R5, and n is 0, 1, 2 or 3;
Rl is an alkyl of up ~o three carbon atoms, or allyl.
R2 and R3 are individually selected from hydrogen,
hydro~y, oxygen, -oR69 sulfur, -SR7 or -NR3R~,
~herein: Zn
R6 is Cl to C4 alkyl or ~
R7 is hydrogen, Cl to Clo alkyl or aryl;
R~ and R9 are the same or different and selected from hydro-
gen, alkyl, haloalkyl, (poly)hydroxy alkyl or (poly)alkoxyalkyl
of up to 6 carbon atoms, alkenyl or alkynyl or up to 3 carbon
atoms, benzyl or substituted benzyl;
with the proviso that at least one of R2 or R3 must be oxygen, -oR6, sulfur,
-SR7 or -NR3R9.
Typical bènzyl substituents for R and R include hologen, nitro
or alkyl. The choice of such substituents would be readily apparent to one
skilled in the art.
Although any compound within the scope of Formula I i8 believed
to have herbicidal activity in accordance with this invention, preferred
compounds are those wherein R is lower alkyl, especially tertiary butyl,
Rl is alkyL, especially methyl and one of R2 or R3 is hydrogen or hydroxy.
The Formula I compounds wherein R2 or R3 is oxygen can be readily
synthesized using available starting materials and using techniques known to
the art, as described, for example, in U. S. Patent Nos. 3,843,67~ and 4,26~,67'~.
. ,~ .
5,~7
Formula I compounds wherein R3 is -oR6 and R2 is hydroxy may be
prepared by reacting an appropriately substituted isoxazolyl imidazolidinone
of the Formula II:
A - ~ N _ ~1
\J
where A and Rl are as previously defined with an alcohol or phenol of the
formula, R60H wherein R6 is as previously defined, in the presence of
an epoxidizing agent, such as m~chloroperoxybenzoic acid. Alternatively,
such compounds may be prepared by reacting, in an anhydrous acidic medium,
an alcohol or phenol of the formula R6o~1 with an isoxazole imidazolidinone
of tlle Formula III: -
III.
A - ~ ~ N -
'~
OH OH
Formula I compound wherein R2 is -oR6 and R3 is llydrogen may be
prepared by reacting, in an acidic reaction medium, an alcohol or phenol of
the formula R601i~ith an isoxazolyl imidazolidinone of the Formula IV:
IV.
A--i~\N--R1
y
OF~ _
wherein A and Rl are as previously defined. Compounds oE the Formulae I:LI
and IV are described, for example, in U. S. Patent No. 4,268,679.
Formula I compounds wherein R2 or R3 are -SR7 may be prepared by
reacting an appropriately substituted thiol with a compound of the Formula IV.
Formula I compounds wherein R2 is =S or -SH may be prepared, for example,
by reacting a Formula IV compound with, for example, phosphorous pentasul-
fide or hydrogen sulfide, respectively. Compounds of the Formula I,
wherein R~ is =S and R3 is -~1, are prepared by reacting, in a suitable sol-
vent, phosphorous pentasulfide with a compound of the Formula V:
V.
o
A - N N
~.1
0~
wherein A and Rl are as previously defined.
Compounds of this invention wherein R2 is -NR~R9 may be prepared
by reacting an isoxazoly-imidazolidinone compound of the Formula IV with a
suitably substituted amine of the formula, NHR8R9, wherein R8 and R9 are as
previously defined. The reaction is typically conducted in an inert
organic solvent medium at up to reflux temperature and usually in the
presence oE a strong mineral or organic acid, e.g., p-toluenesulfonic acid.
The following Examples are illustrative of the preparation of
cer~ain specific compounds of this invention.
Example 1
Preparation of 3-(5-t-butyl-3-isoxazolyl)-1-methyl-
2,4~ dioxoimidazolidine
To a 250 milliliter round bottom flask provided with a magnetic
stirrer and a condenser were charged 5.82 grams (0.035 mole) of 5-t-butyl-
isoxazol-3-yl isocyanate, 5.38 grams (0.035 mole) of sarcosine ethyl ester
hydrochloride, 3.54 grams (0.035 mole) of triethylamine and 100 milliliters
of anhydrous benzene. The reaction mixture was heated at reflux for 19
hours, after which it was cooled, washed with 100 milliliter portions of
water and lO percent aqueous hydrochloric acid and dried over anhydrous
sodiu~n sulfate. Evaporation of solvent afforded 6.61 grams of pale yellow
crystalline solid. The solid was dissolved in ethyl acetate and chromato- -
graphed on 150 grams of E. Merck silica gel using ethyl acetate as the
eluent. Separation of the eluted product fractions and evaporation of
solvent afforded 3.49 grams of pale yellow solid, melting at 113C. to
116C. and identified by N~R, IR and MS analyses as the desired product,
(3-(-5-t-butyl~3-isoxazolyl)-l-methyl-2,4-dioxoimidazolidine.
Example 2
Preparation of 3-(5-t-butyl-3-isoxazolyl)-1-methyl-(4-
hydroxy-2,5-dioxo- and 5-hyd ~
To a 300 milliliter round bottom flask provided with a condenser
and a Dean-Stark trap were charged 4.93 grams (0.025 mole) of 1-(5-t-butyl-
3-isoxazolyl)-3-methyl urea, 2.76 grams (0.03 mole) of glyoxylic acid
hydrate and 100 milliliters of anhydrous benzene. The reaction mixture was
heated at refLux ~or about Lo hours and a small amount of water was col-
lected in the Dean-Stark trap. After cooling, the solvent was evaporated
on a rotary evaporator and the oily viscous residue was dissolved in 100
milliliters of methylene chloride. This solution was washed with 50 mil-
liliters of water and dried over anhydrous sodium sulfate. Subsequent
evaporation of solvent afforded 6.66 grams of pale yellow viscous liquid.
This liquid was chromatographed on 150 grams of E. ~lerck silica gel using
ethyl acetate as the eluent. Two major product fractions were obtained.
After solvent evaporation of these two fractions, there was afforded 2.03
grams of white crystalline solid, rnelting at 131 C to 134 C., identified by
NMR, IR and MS analyses as 3-(5-t-butyl-3-i~soxazolyl)-1-methyl-4-hydroxy-2,5-
dioxoimidazolidine and 2.86 grams of clear colorless viscous liquid (which
crystallized on standing and melted at 103C. to 10~C.) identified by N~R,
IR and MS analyses as 3-5-t-butyl-3-isoxazolyl)-1-methyl-5-hydroxy 2,4-
dioxoimidazolidine.
Example 3
Preparation Of Cis And Trans Isomers Of 3-(5-t-butyl-3-
isoxazolyl)-l-methyl 4-hydroxy-5-methoxy-2-imidazolidinone
Under a nitrogen atmosphere, a solution of 1.8 grarns (0.008 mole)
of 3-(5-t-butyl-3-isoxazolyl)-l-methyl-4~5-dihydro-lH-imidazol-2-one in 40
milliliters of 1:1 V/v methylene chloride:methanol was cooled to 0 to
5C. by Ineans of an ice bath. To this cooled solution was added, with
stirring, 1.72 grams (approx. 0.008 mole) of m-chloroperoxybenzoic acid.
After stirring for about 16 hours, by which time the reaction mixture had
reached room temperature, TLC analysis indicated the presence of some unre-
acted starting material. ~n additional 1.0 gram o~ m-ch1Oroperoxybenzoic
acid was added and stirring was continued an additionaL 4 ilours at room
temperature, at the end of which time, TLC analysis indicated absence ot
unreacted starting material. The reaction mixture was then stripped of
solvent on a rotary evaporator and the residue was takcn up in 70 millili-
ters of chloroform. The solvent solution containing the residue was washed
consecutively with 3 x 35 milliliter portions of 5 percent sodium sulfite
solution, 3 x 35 milliliter portions of 5 percent sodium carbonate solution
and 3 x 40 milliliter portions of water. Subsequent drying oE the organic
layer over anhydrous sulfate and evaporation of solvent a~forded 2.5 grarns
of gummy residue. The residue was dissolved in methylene chloride and
adsorbed on 100 grams of silica gel wet-packed with methylene chloride into
~2~7
a 3.0 x 35 centimeter column. The column was eluted consecutively with 500
milliliters of methylene chloride and 1000 milliliters each of 50:2 V/v,
25:1 V/v and 10:1 V/v methylene chloride:ethyl acetate, 20 milliliter frac-
tions being collected and analyzed by TLC. The appropriate fractions were
combined and stripped of solvent affording a viscous liquid. One combina- -
tion of Eractions was identified by HPLC and I~IR as the pure trans isomer
of the desired product, another combination oE Eractions was identified as
the pure cis isomer, whereas a third combination of fractions was identified
as a mixture of the cis and trans isomers.
lO_xample 4
Preparation of 3-(5-t-butyl-3-isoxazolyl)-1-methyl-4-
hydroxy-5-(2,4-dichlorophenoxy)-2-imidazolidinone
To a stirred mixture, maintained at O to 5 C. by means of an
ice bath, containing 2.0 grams of 3-(5-t-butyl-3-isoxazolyl)-1-methyl-
4,5-dihydro-lH-imidazol-2-one, 4.0 grams of 2,4-dichlorophenol, 3.5 ~rams
of disodi~n hydrogen phosphate and 50 milliliters of methylene chloride
was added 2.5 gr~ns of m-chloroperoxybenzoic acid. ~fter stirring about
16 hours by which time the reaction rnixture had reached room temperature,
TLC analysis indicated complete reaction. The reaction mixture was then
stripped of solvent on a rotary evaporator, the residue taken up in 70
milliliters of chloroform and filtered. The filtrate was washed consecu-
tively with 3 x 30 milliliter portions oE S percent sodium sulfite solu-
tion, 3 x 30 milliliter portions of 0.5 percent sodium hydroxide solution
and 3 x 40 milliliter portions of water. The organic layer was dried
over anhydrous sodium sulfate. Evaporation of solvent afforded 6.0 grams
oE a viscous liquid. Since TLC analysis indicated the presence o~ 2,4-
dichlorophenol, the liquid was dissolved in 100 milliliter oE 1:1 Vlv
~Z~507 7
diethylether:hexane and washed c~nsecutively with 3 x 30 milliliter por-
tions of 1 percent sodium hydroxide and 3 x 30 milliliter portions of
water. The organic layer was then dried over anhydrous sodium sulfate.
Evaporation of solvent afforded 2.7 grams of white solid, which was purified
by column chromatography as follows. The solid was dissolved in methylene
chloride and adsorbed on 55 grams of silica gel wetpacked, with methylene
chloride, into a 2.2 x 32 centimeter column. The column was initially
eluted with 500 milliliters of methylene chloride, 500 milliliters of
20~1 V/v methylene chloride:ethylacetate, and elution was continued while
gradually increasing the ethyl acetate to 10 volume percent, 50 milliliter
fractions being collected and analyzed by TLC. The appropriate fractions
after being combined and stripped of solvent afforded 0.8 grams of mate-
rial identified by HPLC and MS analyses as a mixture of the cis and trans
isomers of the desired product, 3-(5-t-butyl-3-ixoxazolyl)-1-methyl-4-
hydroxy-5-(2,4-dichlorophenoxy)-2-imidazoiidinone.
_xample 5_
~reparation of 3-(5-t-butyl-3-isoxazolyl)-1-methyl-4-
ethoxy-2-imidazolidinone
. _ _ _ __ _ _ _ _ _ _ _ _ _ _ _ . _ _ _ _ _ _
To a 100 milliliter flask were charged 3.4 grams of 3-(5-t-
butyl-3-isoxazolyl)-1-methyl-4-hydroxy-2-imidazolidinone, 60 milliliters
of absolute ethanol and 0.02 grams of p-toluene sulfonic acid. After
stirring for about 24 hours, at room temperature, the flask was stoppered
and allowed to stand quiescent for about 2 days at room temperature. One
milliliter of triethylamine was then added and the reaction ~nixture was
concentrated on a rotary evaporator. The residue was dissolved in 150
milliliters of diethylether washed with three 50 milliliter portions of
water and tile organic layer was dried over anhydrous sodium sulfate.
-- 8 --
~7
Evaporation of solvent ai~orded approximately 3.6 gra[ns of a gummy viscous
material. This rnaterial was dissolved in methylene chloride and chroma-
tographed on silica gel wetpacked into a column ~ith methylene chloride.
The column was eluted consecutively with 100 milliliters of methylene
chloride and 400 milliliters each of 100:1 V/v, S0:1 V/v and 50:15 V/v
methylene chloride:ethylacetate, 100 ~nilliliter eluent fractions being
collected and analyzed by TLC. Combination of the appropriate fractions
and removal of solvent afforded 2.6 grams of gummy material identified as
3-(5-t-butyl-3-isoxazolyl)-1-methyl-4-ethoxy-2-imidazolidinone.
E mple 6
Following the procedure described in Example 5, but using methanol
in place of ethanol, the compound, 3-(5-t-butyl-3-isoxazolyl)-1-methyl-4-
methoxy-2-imidazolidinone was prepared.
Example 7
Preparation of 3-(5-t-butyl-3-isoxazolyl)-1-methyl-4- and 5-
butylthio-2-imidazolidinone
_____ ~____._. __ _ ___ _ _ ___ _ _ ___ _
To a flask provided with a reflux condenser was charged 6.0
gr~ns of 3-(5-t-butyl~isoxazolyl)-1-methyl-4-hydroxy-2-imidzaolidinone,
0.2 gram of p toluene suifonic acid~ 7.0 milliliters of butanethiol and
300 milliliters of benzene. The reaction mixture was heated to reflux and
maintained at reflux for about 2-1/2 hours, the progress of the reaction
being monitored by TLC. The reaction mixture was then cooled, transferred
to a separatory funnel and washed consecutively with 3 x 70 miLliliter
portions of saturated sodium bicarbonate solution and 3 x 50 milliliter
portions of water. ~le organic layer was dried over anhydrous sodium
sulfate and stripped of solvent affording 7.5 grams of colorless gummy
0~
liquid, which was puriEied by column chromatography. .~ore particularly,
the product was dissolved in methylene chloride and adsorbed onto 145 grams
of silica gel wet-packed with methylene chloride into a 2.5 x 58 centimeter
column. The column was eluted with methylene chloride and 4:1 V/v methylene
chloride: ethyl acetate and the eluent fractions (about l00 milliliters) were
analyzed by TLC. Combination of appropriate fractions and evaporation of
solvent afforded 2.5 grams of product identified as 3-(5~t-butyl-3-isoxazolyl)-
l-methyl-5-butylthio-2-imidazolidinone and 0.4 gram of product identified
as 3-(5-t-butyl-3-isoxazolyl)-1-methyl-4-butylthio-2-iunidazolidinone.
Example 8
Preparation of 3-(5-t-butyl-3-isoxazolyl)-1-methyL-4-
thio-2-imidazolidinone
_ _ _ _ ______. _.__ _ _ _ _ _ __ _ ._ _ _ _ __ _ _ _
A mixture of 3.22 grams 3-(5-t-butyl-3-isoxazolyl)-1-methyl-4-
hydroxy-2-imidazolidinone, 3.0 grams of phosphorous pentasulfide, 5 miLli-
liters of HMPTA and 75 milliliters of benzene was heated to reflux and
maintained at reflux for about 3 hours, the progress of the reaction being
monitored by TLC. The reaction mixture was then cooled, transferred to a
separatory funnel, diluted with 50 milliliters of benzene and washed with
6 x 100 miLliLiter portions of water. The organic layer was dried over
anhydrous sodium sulfate and stripped of solvent affording 3.5 grams of
viscous gummy residue ~hich was further purified by column chromatography.
More particularly, the residue was dissolved in rnethylene chloride and
adsorbed on 60 grarns of silica gel wet-packed with rnethylene chloride into
a 2.2 x 30 centime~er column. The column was eluted consecutively with
methylene chloride (400 ml.), 99:1 V/v methylene chloride:ethyl acetate
(200 ml.) and 400 milliliter portions each of 49:1 V/v, 25:1 V/v and 12:1 V/v
methylene chloride:ethyl acetate, the eluent fractions being analyzed by TLC.
-- 10 --
~7
Combination of appropriate fractions and evaporation of solvent afforded
0.2 gram of light yellowish 801id, identified by spectral analyses as
3-(5-t-butyl-3-isoxazolyl)-1-methyl-4-thio-2-iTnidazolidinone .
Exam le 9
Preparation of 3-~5-t-butyl-3-isoxazolyl)-1-methyl-4-
mercapto-2-imidazolidinone
__ _ _ _ _ _ ____ _ _ ___ _ __ _ , _ _ _ _ _
To a 250 milliliter 3-necked flask provided with a dry-ice
acetone condenser, gas inlet tube and a stopper were charged 2.5 grams of
3-(S-t-butyl-3-isoxazolyl)-l-methyl-4-hydroxy-2-imidazolidinone and 20
milliliters of anhydrous diethyl ether. The flask contents were cooled in
a dry-ice acetone bath and about 40 grams of gaseous hydrogen sulfide were
slowly condensed into the flask. After 2 hours stirring TLC analysis
indicated no reaction so the reaction mixture was removed from the bath,
and the liquid hydrogen sulfide was permitted to reflwc. After refluxing
for about one hour, TLC analysis indicated no reaction. At thi~s point
50 milliliters o~ tetrahydrofuran were added, stirring was continued for
another hour ancl 0.15 gram of ~`~UERLYST~ -15 was aclded and stirring continued
another hour. Since TLC allalysis stilL indicated no reaction, the flask was
repLaced in the dry-ice acetone bath, the condenser was EilLed with dry-ice
acetone and stirring continued. After about 18 hours stirring, by which
time the Tflask contents had warmed to room temperature, TLC analysis indi-
cated some reaction. About 0.03 gram of p-toluene sulfonic acid was added
and stirring was continued for about 24 hours at room temperature. Since
TLC analysis indicated no further reaction, the flask contents were fiLtered
and concentrated on a rotary evaporator to about 50 percent volume. ~bout
5 milliliters of triethylamine was then added and solvent was co,npletely
evaporated. ~le liquid residue was taken up in lO0 milliliters of ethyl
acetate and washed with 4 x 50 milliliter portions of water. The organic
layer was dried over anhydrous sodium sulfate and solvent was evaporated
affording about 10 grams of white solid which was further purified by
column chromatography. More particularly, the solid was dissolved in
methylene chloride and adsorbed on 150 grams of silica gel wet-packed with
methylene chloride into a 2.5 x S6 centimeter column. The column was
eluted with 2000 milliliters of 49:1 V/v methylene chloride:ethyl acetate
and 1500 milliliters of 24:1 V/v methylene chloride:ethyl acetate, 125 mil-
liliter eluent fractions being collected and analyzed by TLC. The appro-
priate fractions were combined and solvent was evaporated affording about
1.0 gram of product, identified by spectral analyses as 3-(5-t-butyl-3-
isoxazolyl)-l-methyl-4-mercapto-2-imidazolidinone.
Example 10
Preparation of: 3-[5-t-butyl-3-isoxazolyl]-1-methyl-4-(N-benzyl)
amino-2-imidazolidinone
,____ _ _ ___ ___ _ ~__ __ __ _____ _._
To a 50 milliliter flask provided with a magnetic stirring bar,
~ean-Stark trap and a reflux condenser were charged 1.5 grams (0.0063 mole)
of 3-[5-t-butyl-3-isoxazolyl]-1-methyl-4-hydroxy-2-imidazolidinone, 1.10
grams (0.01 mole) of benzylarnine, 0.15 gram of p-toluenesulfonic acid and
20 milliliters of toluene. The resulting pale yellow solution ~fas heated
to reflux and maintained at reflux until TLC analysis indication complete
conversion of starting materials. The reaction mixture was then cooled,
transferred to a separatory funnel~ diluted with 75 milliliter of ethyl
acetate, and washed consecutively with 100 milliliter portions of saturated
sodium bicarbonate and saturated sodium chloride solutions. The organic
layer was dried oYer anhydrous magnesium sulfate, filtered and concentrated
in vacuo affording 2.21 grams of a golden oil identified by NMR and MS
___
analyses as the desired product.
- 12 -
.
~LZO~
E mple 11
Preparation of: 3-[5-t-butyl-3-isoxazolyl]-1-methyl-4~ -benzyl-
N-methyl)amino-2-imidiazolidinone
. ____ _ __ ___ __ _ ___ ___ ___ _ _.__ __
To a 50 rnilliliter flask provided with a magnetic stirring bar,
Dean-Stark trap and a reflux condenser were charged 2.0 grams (0.0084 mole)
of 3-[5-t-butyl-3-isoxazolyl]-l-methyl-4-hydroxy-2-imidazolidinone, 1.45
gr~ls (0.012 mole) o~ benzylmethylamine, 0.13 gram of p-toluenesulfonic
acid and 20 milliliters of toluene. The resulting pale yellow solution ~as
heated to reflux and maintained at reflllx until TLC analysis indicated
complete conversion of starting materials. The reaction mixture was then
cooled, transferred to a separatory funnel, diluted with 75 millilters of
ethyl acetate and washed consecutively with 100 milliliter portions of
saturated sodium bicarbonate and sat~lrated sodium chloride solutions. The
organic layer was dried over anhydrous magnesium sulfide, filtered and
concentrated in vacuo affording 2.80 grams of yellow oil identified by MMR
and ~IS analyses as the desired product.
Lxample l_
Preparation of: 3-[5-t-butyl-3-isoxazolyl]-1-methyl-4-amino-2-
lmidazolidinone _ _ _ _ _
To a Paar hydrogenation bottle was charged 3.10 grams (0.0095 mole)
of 3-[5-t-butyl-3-isoxazolyl]-1-methyl-4-(~-benzyl)amino-2-imidazolidinone
(prepared as described in Example lO), 200 milliliters of glacial acetic acid
and 0.4 gram of 10 percent palladium on carbon hydrogenation catalyst. The
bottle was charged with hydrogen and rocked 20 hours in a Paar hydrogenation
apparatus under a hydrogen atmosphere. The bottle was flushed with air,
the cataiyst removed by fi].tration through a bed of CELIrL'~ and the reaction
mi~t~lre was _oncentrated in vacuo to remove most of the acetic ac;d solvent.
- 13 -
The residue was dissolved in chlorobenzene and remaining acetic acid was
removed azeotropically. The residue was then dissolved in chloroform,
dried over anydrous mangesium sulfate, filtered and concentreate in vacuo
affording 2.~7 grams of brown oil identified by NMR and ~S analyses as the
desired product.
Example 13
Preparation of: 3-[5-t-butyl-3-isoxazolyl]-1-methyl-4-amino-2-
imidazolidinone hydrochloride _ _ _ _ _
To a 250 milliliter flask provided with a magnetic stirring bar
and fitted with a glass delivery tube attached to a hydrogen chloride gas
cylinder were charged 1.2 grams (0.0051 mole) of 3-[5-t-butyl-3-isoxazolyl]-
l-methyl-4-amino-2-imidazolidinone (prepared as described in Example 12)
and 120 milliliters of diethylether. The flask contents were cooled to
0C. and hydrogen chloride gas was bubbled into the solution, a white
precipitate fo ~ling immediately. Addition of hydrogen chloride gas was
continued for ten minutes after which the reaction mixture was stirred at
0C. ior one hour. The precipitate was removed by suction filtration in
a ~iltered glass funnel, washed with 2x20-milliliter portions of diethyl
ether ancl air dried af~ording 0.56 grams of material identified by ~R
analysis as the desired product.
_xample 14
Preparation of: 3-[5-t butyl-3-isoxazolyl)-1-methyl-4-(N-2-
propynyl) amino-2-imidazolidinone
. ~ . ~
To a 50 milliliter flask provided with a magnetic stirring bar
and a reflux condenser was charged 1.50 grams (0.0063 mole) of 3-[5-t-butyl-
3-isoxazolyl]-1-methyl-4-hydroxy-2-imidazolidinone, 0.55 gr,~n (0.010 mole)
- 14 -
~5~
of propargylamine, 0.1 gram of p-toluenesulfonic acid and 15 milliliters
of dry toluene. The stirred reaction mixture was slowly heated to about
60C. and ma;ntained there at overnight, after which it was cooled and an
aliquout analyzed by ~PLC which indicated the presence of about 13 percent
unreacted starting material. An additional 0.5 gram of propargylamine was
added and the stirred reaction mixture was heated to and maintained at 60C.
for 6 hours after which time ~iPLC analysis indicated the presence of 8.2
per cent unreacted starting material. An additional 0.5 graln o~ propargyl-
amine and 0.2 gram of p-toluenesulfonic acid were added and the reaction
mixture was stirred overnight at 60~C., HPLC analysis at the end of this
time indicating complete consumption of starting material. The cooled
reaction mixture was transferred to a separatory funnel, diluted with 100
milliliters of ethyl acetate and washed consecutively with lO0 milliliters
portions of saturated sodium bicarbonate and sodium chloride solutions.
The organic layer was dried over anhydrous sodium sulfate, ~iltered and
concentrated in vacuo affording 2.~5 grams of an orange oil which was
purified by col~ln chromatography affording 1.44 grams of a yellow oil,
identified by NMR and ~R analyses as the desired product.
Exam-ple 15
Preparation of: 3-[5-(t-butyl-3-isoxazolyl]-l-methyl-4-(N-meth-yl)
amino-2-imidazolidinone
To a Paar hydrogenation bottle was charged 4.0 grams (0.012 mole)
of 3-[5-t-butyl-3-isoxazolyl]-l-methyl-4-(N-benzyl-N-methyl)amino-2-imidaæoli-
dinone (prepared as described in Example ll), 150 milliliters of glacial
acetic acid and 0.61 gram of 10 percent palladium on carbon hydrogenation
catalyst. The bottle was charged with hydrogen and rocked 6 hours in a Paar
hydrogenation apparatus under a hydrogen atmosphere. The bottle was flushed
with air, the catalyst removed by filtration through a l~ed of CELITE~) and
the reaction mixture was concentrated _n vacuo to remove most of the acetic
ac id solvent . The residue was d issolved in chlorobenzene and remaining
acetic acid was removed azeotropically. The residue was dissolved in 250
milliliters of chloroform, dried over anhydrous sodium sulfate, filtered
and concentrated l_cuo affording an orange oil which was further puri-
fied by d igestion with hexane followed by filtration and concentration in
vacuo affording 2.7~ grams of orange oil identified by NMR and I~IS analyses
as the desired produc t.
Example 16
Preparation of: 3-[5-t-butyl-3-isoxazolyl]-1-methyl-4-(2-
hydroxyethyl) amino-2-imidazolidinone
___ ___ _ _ _ _ ___ _._ ._ _ _ __ _ ._ _
To a lOO milliliter flask provided with a magnetic stirring bar,
a Dean-Stark trap and a reflux condenser were charged 5.0 grams (0.021
mo].e) of 3-[5-t-butyl-3-isoxazolyl]-1-methyl-4-hydroxy-2-imidazolidinone,
1.~3 ~rams (0.028 mole) of ethanolamine, 0.23 gram of p-toluenesulfonic
acid and 60 milliliters of toluene. The mixture was heated to reflux and
maintained at refLux for one hour, at the end of which tirne TLC analysis
indicated presence of some unreacted starting material. An additional 0.
gram of ethanolamine was added and refluxing continued for ~ hours. The
reaction mixture was cooled, transferred to a separatory funnel, diluted
with 75 millil iters of ethyl acetate and washed with a 100 milliliter
portion of saturated sodium chloride solution. rhe organic layer was dried
over anhydrous magnesium sulfate, filtered and concentrated _n vacuo
affording 5.81 grarns of an organ oil identified by NM~ and ~IS analyses as
the desired produc t .
~w~ ~
~xample l7
Preparation of: 3-[5-t~b~ltyl-3-isoxa~olyll-1-methyl-4-(~-2-
propenyl ? amino-2-imidaæolidinone _ _
To a 50 milliliter flask provided a magnetic stirring bar and a
reflux condenser were charged 1.67 grams (0.7 mole) of 3-[5-t-butyl-3- -
isoxazolyl¦-l-methyl-4-hydroxy-2-imidazolidinone, 0.15 gram of p-toluene-
sulfonic acid, 15 milliliters of toluene and 1.1 gram (0.018 mole) of allyl
amine. After a total of 22 hours relux (an additional 1.0 gram of allyl-
amine being added after 18 hours reflux), the reaction mixture was cooled,
solvent was removed in vacuo, the oily residue was dissolved in 100 milli-
liters of ethyl acetate and washed consecutively with 100 milliliter por-
tions of saturated sodium bicarbonate and sodium chloride solutions. The
organic layer was dried over anhydrous magnesium sulfate, filtered and
concentrated in vacuo affording 1.90 grams of material, identified by N~IR,
MS and IR analyses as the desired product.
Examp]e 18
-
Preparation of: 3-[5-t-butyl-3-isoxazolyl]-1-methyl-4-(~nethyl-
N-2-propenyl)amino-2-imidazolidinone
__ _ __ _ _ _ _._ _ __ . _ ~_ ._._ __ __ .___ . _ _ ~_ _
To a 100 milliliter flask provided with a magnetic stirring bar,
a Dean-Stark trap and a reflux condenser were charged 3.0 gr~ns ~0.0125
mole) of 3-[5-t-butyl-3-isoxazolyl~ methyL-4-hydroxy-2-imidazolidinone,
1.13 gram (0.016 mole) of N-methyl-N-allylamine, 0.2 gram of p-toluene-
sulfonic acid and 40 milliliters of benzene. The reaction mixture was
refluxed overnight and as TLC analysis indicated incomplete conversion of
starting material, an additional 0.7 gram of N-methyl-N-allylamine was
added and refLuxing was continued for 7 hours. Since TLC analysis indicated
the presence oE some starting material, 0.2 gram of p-toluenesulEonic
- 17 -
acid was added and refl~ing was continued overnight and an additional
two days during which period 1.0 gram of ~-methyl-N-allylamine was a~ded
each day. The reaction mixture was cooled to room temperature, transferred
to a separatory funnel, diluted wi~h 75 milliliters of ethyl acetate and
washed consecutively with 100 milliliter portions of saturated sodium
bicarbonate and sodium chloride solutions. The organic layer was dried
over anhydrous sodium sulfate, filtered and concentrated ln vacuo affording
3.53 grams of light brown solid. The solid was dissolved in methylene
chloride and crystallized from a 75:25 volume/volume mixture of methylene
chloride: hexane affording 1.18 grams of light tan needle-like crystals
identified by N~R analysis as the desired product.
Example 19
Preparation of: 3-[5-t-butyl-3-3-isoxazolyl]-1-methyl-4-(N-ethyl-
N-benzyl)amino-2-imidazolidinone.
____ _ ~ _ _ _ _ _ _ _ __ _
To a lO0 milliliter flask provided with a magnetic stirring bar,
a Dean-Stark trap and a reflux condenser were charged 4.0 grams (0.0167
mole) of 3-(5-t-butyl-3-isoxazolyl¦-1-methyl-4-hydroxy-2-imidazolidinone~
2.7 grams (0.020 mole) of N-ethylbenzlamine, 0.1 gram of p-toluenesulfonic
acid and 60 milliliters of toluene, forming a brown heterogeneous reaction
mixture. The mixture was heated to reflux, resulting in formation of an
orange solution, and maintained at reflux for about 7 days. The reaction
mixture was cooled to room temperature (a light fan precipitate being
observed upon cooling), transferred to a separatory ~funnel, diluted with 100
milliliters of ethyl acetate and washed with 100 milliliters of saturated
sodium bicarbonate solution resulting in dissolution of the precipitate.
The organic layer was washed with 100 milliliters of saturated sodium
chloride solution, dried over anhydrous magnesium sulfate, filtered and
,,~7
concentrated in vacuo aEEording a brown viscous oil. L'he oil was digested
with hexane, cooled to 0C., filtered and the filtrated concentrated in
va affording 6.69 grams of medium brown oil, ;dentified by NM~ analysis
as the desired product.
Example 20
Preparation of: 3-[5-t-butyl-3-isoxazoIyl]-l-methyl-4-(N-ethyl)-
amino-2-imidazolidinone _ _ _ _ __
To a Paar hydrogenation bottle was charged 4.5 gram~ (0.126 mole) of
3-[5-t-butyl-3-isoxazolyl]-1-methyl-4-(N-ethyl-N-benzyl)amino-2-imidazolidinone
(prepared as described in Exarnple 19), 150 milliliters of glacial acetic acid
and 0.5 gram of 10 percent palladium on carbon hydrogenation catalyst. The
bottle was charged with hydrogen at a pressure of 50 psi and rocked ~ hours
in a Paar hydrogenation apparatus under a hydrogen atmosphere. The bottle
was flushed with air, catalyst was removed by filtration through a nylon
Eilter and the reaction mixture was concentrated 1 _ cuo to remove most of
the acetic acid solvent. The residue as treated with 200 milliliters o~
chlorobenzelle and the remaining acetic acid was removed azeot~opically. The
residue was dissolved in 200 milliLters of chloro~orm, dried over anhydrous
magnesi~ml sulfate, Eiltered and concentrated in vacuo afEording 4.0 grams of
brown oil identi~ied by NMR and i~S analyses as the desired product.
Example 21
___
Preparation of: 3-[5-t-butyl-3-isoxazolyl]-1-methyl-4-(N-2-methoxy-
ethyl)amino-2-imidazolidinone.
__ ~ __ _ _ _ _ _ _ . _ _ . _ _. _ _ _ _ _ __ _ . _._ _ _
To a 50 milliliter flask provided with a magnetic stirring bar, a
Dean-Stark trap and a relux condenser were charged 1.2 gr~ns (0.005 mole) of
3-(5-t-butyl-3-isoxazolyl]-1-1nethyl-4-hydroxy-2-imidazolidinone, 0.45 gram
-- 1 :3 --
~Z05~77
(0.06 mole) of methoxyethylamine, 0.2 gram of p-toluenesulfonic acid and
15 milliliters of toluene. The reaction mixture was heated to reflux and
maintained at reflux until TLC analysis indicated complete conversion of
starting material. The reaction mixture was cooled to room temperature,
transferred to a separatory funnel, diluted with 120 milliliters of ethyl
acecate and washed consecutively with 100 milliliter portions of saturated
sodium bicarbonate and saturated sodium chloride solutions. The organic
layer was dried over anhydrous magnesium sulfate, filtered and concentrated
in vacuo affording 1.35 grams of an orange oil identified by NMR and MS
analyses as the desired product.
Although preparation of certain compounds of the invention have
been illustrated in some detail by the foregoing, it is to be understood
that other compounds of the invention may be readily prepared by those
skilled in the art using the same or similar syntheses and by varying the
choice of starting materials.
Weed control in accordance with this invention is ef~ected by
application, either before or after emergence of weeds~ of a herbicidalLy
effective amount of a cornpound of this invention. It is, of course, to
be understood that the term "a compound oE this invention" also includes
rni~tures of such compounds.
The term "herbicidally effective amount" is that amount of a
compound of this invention required to so injure or damage weeds such that
the weeds are incapable of recovering following application. The quantity
of a compound of this invention applied in order to exhibit a satisfactory
herbicidal effect may vary over a wide range and depends on a variety of
Eactors, sucll as, for example, hardiness of a particular weed species,
extent of weed infestation, climatic conditions, soil conditions, method
- 20 -
~;077
of application, and the like. Typically, as little as one or less pound per
acre of a compound of this invention would be expected to provide satisfac-
tory weed control, although in some instances appl ication rates in excess
of one pound per acre; e.g., up to 5 or more pounds per acre might be
required. Of course, the efficacy of a particular compound against a
particular weed species may readily be determined by routine laboratory
or field testing in a manner well known to the art. It is expected that
satisfactory weed control can be had at a rate of application in the range
of 0.1 to 1. 0 pound per acre.
Of course, a compound of this invention can be formulated accord-
ing to routine methods with any o several known and commonly used herbici-
dal diluents, adjuvants and carriers. The forrnulations can contain liquid
carriers and adjuvants such as organic solvents, as well as emulsifiers,
stabilizers, dispersants, suspending agents, spreaders, penetrants, wetting
agents and the like. Typical carriers utilized in dry formulations include
clay, talc, diatornaceous earth, silica and the like. Preferred formula-
tions are those in the form of wettable powders, flowables, dispersible
granulates or aqueous emulsifiable concentrates which can be diluted with
water at the site of application. Also, dry formulations such ns granules,
20 dusts, and the Like, may be used.
When desired, a compound of this invention can be appl ied in com-
bination witll other herbicidal agents in an effort to achieve even broader
vegetative control. Typical herbicides which can be conveniently combined
with liormula I compound include atrazine, hexazinone, metribuzin, ametryn,
cyanazine, cyprazine, prometon, prometryn, propazine, simazine, terbutryn,
propham, alachlor, acifluorfen, bentazon, metolachlor and N,N-dialkyl
thiocarbamates such as EPTC, butylate or vernolate. These, a~s well as other
-- 21 --
lZOSO~
herbicides described, for example, in the Herbicide Handbook oE the Weed
Science Society of America, may be used in combination with a compound or
compounds of the invention. Typically such formulations will contain from
about 5 to about 95 percent by weight of a compound of this invention.
The herbicidal formulations contemplated herein can be applied by
any of several methods known to the art. Generally, the formulation will
be surface applied as an aqueous spray. Such application can be carried
out by conventional ground equipment, of if desired, the sprays can be
aerially applied. Soil incorporation of such surface applied herbicides is
accomplished by natural leaching, and is of course facilitated by natural
rainfall and melting snow. If desired, however, the herbicides can be
ineorporated into the soil by conventional tillage means.
Compounds of this invention are believed effective for preemer-
gence or postemergence control of a wide variety of broadleaf and grassy
weeds. Typical of the various species of vegetative growth that may be
eontrolled, combated, or eliminated are, for example, annuals such as
pigweed, lambsquarters, foY.tail, crabgrass, wild mustard, field pennycress,
ryegrass, goose grass, chickweed, wild oats, velvetleaf, purslane, barn-
yardgrass, smartweed, knotweed, cocklebur, kochia, medic, ragweed, hemp
nettle, spurrey, pondweed, carpetweed, morningglory, ducksalad, cheatgrass,
fall panicum, jimsonweedg witchgrass, watergrass, wild turnip, and simi]ar
annual grasses and weeds. Biennials that may be controlled include wild
barley, campion, burdock, bull thistle, roundleaved mallow, purple star
thistle, and the lilce. Also controlled by the compounds of this invention
are perennials such as quackgrass, Johnsongrass~ Canada thistle, curly dock,
~ield chickweed, dandelion, Russian Icnapweed aster, horsetaiL ironweed,
sesbania, cattail, wintercress, horsenettle, nutsedge, milkweed, ~sicklepod,
and the like.
~$~7
The compo~mds prepared as described in Examples 1 and 2 were
individually tested for herbicidal efficacy, against a variety of broadleaf
and grassy weed species, under controlled laboratory conditions of light,
humidity and temperature. Solvent solutions of said compounds were applied,
both preemergence and postemergence, to test flats containing the various
weed species, and herbicidal efficacy was determined by visual inspection,
periodically after application of the compounds. ~erbicidal efficacy was
determined on a scale of from 0 (no injury) to 10 (all plants dead). For
example, the compounds of Example 2 were found effective at rates of
application as low as 0.5 pound per acre in controlling teaweed, imsonweed,
coffeeweed, velvetleaf, tall morningglory, yellow foxtail, large crabgrass,
Johnsongrass, wild oats and barnyard grass, herbicidal injury ratings
ranging from 8 to 10 having been observed for these compounds up to 21 days
subsequent to application.
Each of the cis and trans isomers of the Example 3 compound was
found effective, when applied preemergence at a rate of 1.0 pound per acre,
in controlling teaweed, jimsonweed, wild mustard, cofEeeweed, velvetleaf,
tall morningglory, yellow foxtail, large crabgrass, Johnsongrass and wild
oats, herbicidal inury ratings of from 8 to 10 having been observed for
these compounds up to 21 days subsequent to application. These compounds
were also found effective, when applied postemergence at a rate of 1.0
pound per acre, in controlling teaweed, jimsonweed, wild mustard, coffee-
weed, velvetleaf and tall morningglory.
Similar preemergence and postemergence herbicidal efficacies
were observed using the compounds prepared as described in Examples 4, 5
and 6.
- 23 -
' ~50~7 .
The 4-butylthio compou~d prepared as described in Example 7, when
applied preemergence at a rate of 1.0 pound per acre, was found effective
in controlling teaweed, jimsonweed, wild mustard, coffeeweed, velvetleaf,
tall morningglory, yellow foxtail, large crabgrass, Johnsongrass and wild
oats, herbicidal injury ratings of from 8 to 10 having been observed up to 21
days following application. Similar preemergence herbicidal activities were
observed with the compounds prepared as described in Examples 8 and 9.
- The said Rxample 7 compound was also observed to be eEfective
in controlling jimsonweed, wild mustard, coffeeweed and tall morningglory
when applied postemergence at a rate of 1.0 pound per acre.
'~le compounds prepared as described in Examples 10 through 21
were individually tested for herbicidal efficacy, against a variety of
broadleaf and grassy weed species, under controlled laboratory conditions
of light, hwnidity and temperature. Solvent solutions of said compounds
were applied, both preemergence and postemergecce, to test flats containing
the various weed species, and herbicidal efficacy was determined by visual
in~pection, periodically after application of the compounds. ~lerbicidal
efficacy was determined on a scale of from 0 (no injury) to 10 (all plants
dead). The cornpounds of Examples 10 through 21 were found effective at
rates of application as low as l.0 pound per acre in both preemergence and
postemergence control teaweed, jimsonweed, wild mustard coffeeweed, velvet-
leaf~ tall morningglory, yellow foxtail, large crabgrass, Johnsongrass,
wild oats and barnyard grass, herbicidal injury ratings averaging in the
range of from 8 to 10 having been observed for these compounds up to 23
days subsequent to application.
t~lthough the invention has been desc-ribed in considerable detail
by the Eoregoing, it is to be understood that many variations may be made
therein by those skiLled in the art without departing from the spirit and
scope thereof as deEined by the appended claims.
24 -
