CA1205077A - Herbicidally active 3-isoxazolyl-2-imidazolidinone derivatives - Google Patents
Herbicidally active 3-isoxazolyl-2-imidazolidinone derivativesInfo
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- CA1205077A CA1205077A CA000450478A CA450478A CA1205077A CA 1205077 A CA1205077 A CA 1205077A CA 000450478 A CA000450478 A CA 000450478A CA 450478 A CA450478 A CA 450478A CA 1205077 A CA1205077 A CA 1205077A
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- Prior art keywords
- methyl
- butyl
- isoxazolyl
- imidazolidinone
- compound
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
- A01N43/80—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms five-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,2
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Agronomy & Crop Science (AREA)
- Pest Control & Pesticides (AREA)
- Plant Pathology (AREA)
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- Engineering & Computer Science (AREA)
- Dentistry (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Zoology (AREA)
- Environmental Sciences (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
Abstract of the Disclosure 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
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--~<
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-
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--~<
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-
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-
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.
~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.
~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
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.
~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.
~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.
.
~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.
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) ~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 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 ~;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 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.
' ~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.
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.
.
~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.
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) ~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 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 ~;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 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.
' ~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.
Claims (14)
IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A compound of the formula:
wherein A is or 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, cyclo-pentyl, and cyclohexyl, a haloalkyl of up to six 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, or where Z is nitro (-N02, chloro (-Cl), bromo (-Br), fluoro (-F), or R5, and n is 0, 1, 2 or 3;
R1 is an alkyl of up to three carbon atoms, or allyl;
and R2 and R3 are individually selected from hydrogen, hydroxy, oxygen, -OR6, sulfur, -SR7 or -NR8R9, wherein:
R6 is C1 to C4 alkyl or R7 is hydrogen, C1 to C10 alkyl or aryl;
R8 and R9 are the same or different and selected from hydro-gen alkyl, haloalkyl, (poly)hydroxy alkyl or (poly)alkoxyalkyl or up to 6 carbon atoms, alkenyl or alkynyl or up to 3 carbon atoms, benzyl or benzyl substituted with halogen, nitro or alkyl;
with the proviso that at least one of R2 or R3 must be oxygen,-OR6, sulfur, -SR7 or -NR3R9.
wherein A is or 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, cyclo-pentyl, and cyclohexyl, a haloalkyl of up to six 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, or where Z is nitro (-N02, chloro (-Cl), bromo (-Br), fluoro (-F), or R5, and n is 0, 1, 2 or 3;
R1 is an alkyl of up to three carbon atoms, or allyl;
and R2 and R3 are individually selected from hydrogen, hydroxy, oxygen, -OR6, sulfur, -SR7 or -NR8R9, wherein:
R6 is C1 to C4 alkyl or R7 is hydrogen, C1 to C10 alkyl or aryl;
R8 and R9 are the same or different and selected from hydro-gen alkyl, haloalkyl, (poly)hydroxy alkyl or (poly)alkoxyalkyl or up to 6 carbon atoms, alkenyl or alkynyl or up to 3 carbon atoms, benzyl or benzyl substituted with halogen, nitro or alkyl;
with the proviso that at least one of R2 or R3 must be oxygen,-OR6, sulfur, -SR7 or -NR3R9.
2. A compound of claim 1 wherein R is tertiary butyl and R1 is methyl.
3. A compound of claim 1 wherein either or both of R2 or R3 are oxygen.
4. A compound of claim 3 selected from 3-(5-?-butyl-3-isoxazolyl)-1-methyl-2,4-dioxoimidazolidine, 3-(5-?-butyl-3-isoxazolyl)-1-methyl-4-hydroxy-2,5-imidazolidine and 3-(5-?-butyl-3-isoxazolyl)-1-methyl-5-hydroxy-2,4-imidazolidine.
5. A compound of claim 1 wherein either or both of R2 or R3 are -OR6.
6. A compound of claim 5 selected from 3-(5-?-butyl-3-isoxazolyl)-1-methyl-4-hydroxy-5-methoxy-2-imidazolidinone, 3-(5-?-butyl-3-isoxazolyl)-1-methyl-4-methoxy-2-imidazolidinone, 3-(5-?-butyl-3-isoxazolyl)-1-methyl-4-ethoxy-2-imidazolidinone and 3-(5-?-butyl-3-isoxazolyl)-1-methyl-4-hydroxy-5-(2,4-dichlorophenoxy)-2-imidazolidinone.
7. A compound of claim 1 wherein either or both of R2 or R3 are sulfur or -SR7.
8. A compound of claim 7 selected from 3-(5-?-butyl-3-isoxazolyl)-1-methyl-4-butylthio-2-imidazolidinone, 3-(5-?-butyl-3-isoxazolyl)-1-methyl-4-mercapto-2-imidazolidinone and 3-(5-?-butyl-3-isoxazolyl)-1-methyl-4-thio-2-imidazolidinone.
9. A compound of claim 1 wherein either or both of R2 or R3 are -NR8R9.
10. A compound of claim 9 selected from 3-[5-?-butyl-3-isoxazolyl]-1-methyl-4-(N-benzyl)amino-2-imidazolidinone, 3-[5-?-butyl-3-isoxazoly]-1-methyl-4-(N-benzyl-N-methyl)amino-2-imidazolidinone, 3-[5-?-butyl-3-isoxazoly]-1-methyl-4-amino-2-imidazolidinone, 3-[5-?-butyl-3-isoxazolyl]-1-methyl-4-amino-2-imidazolidinone hydrochloride, 3-[5-?-butyl-3-isoxazolyl)-1-methyl-4-(N-2-propynyl)amino-2-imidazolidinone, 3-[5-(?-butyl-3-isoxazolyl]-1-methyl-4-(N-methyl)amino-2-imidazolidinone, 3-[5-t-butyl-3-isoxazolyl]-1-methyl-4-(2-hydroxyethyl)-amino-2-iunidazolidinone, 3[5-?-butyl-3-isoxazolyl]-1-methyl-4-(N-2-propenyl) amino-2-imidazolidinone, 3-[5-?-butyl-3-isoxazolyl]-1-methyl-4-(N-methyl-N-2-propenyl)amino-2 imidazolidinone, 3-[5-?-butyl-3-isoxazolyl]-1-methyl-4-(N-ethyl-N-benzyl)amino-2-imidazolidinone, 3-[5-?-butyl-3-isoxazolyl]-1-methyl-4-(N-ethyl)-amino-2-imidazolidinone, and 3-[5-?-butyl-3-isoxazolyl]-1-methyl-4-(N-2-methoxyethyl)amino-2-imidazolidinone.
11. The method of controlling the growth of weeds wherein a herbicidally effective amount of herbicide is applied to a growth medium prior to emergence of weeds therefrom or to the weeds subsequent to emer-gence from the growth medium wherein the improvement resides in using as the herbicide a compound or mixture of compounds as defined in claim 1.
12. The method of controlling the growth of weeds wherein a herbicidally effective amount of herbicide is applied to a growth medium prior to emergence of weeds therefrom or to the weeds subsequent to emergence from the growth medium wherein the improvement resides in using as the herbicide a compound or mixture of compounds as defined in claim 2, 3 or 4.
13. The method of controlling the growth of weeds wherein a herbicidally effective amount of herbicide is applied to a growth medium prior to emergence of weeds therefrom or to the weeds subsequent to emergence from the growth medium wharein the improvement resides in using as the herbicide a compound or mixture of compounds as defined in claim 5, 6 or 7.
14. The method of controlling the growth of weeds wherein a herbicidally effective amount of herbicide is applied to a growth medium prior to emergence of weeds therefrom or to the weeds subsequent to emergence from the growth medium wherein the improvement resides in using as the herbicide a compound or mixture of compounds as defined in claim 8, 9 or 10.
Applications Claiming Priority (8)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US47923283A | 1983-03-28 | 1983-03-28 | |
| US479,232 | 1983-03-28 | ||
| US49081983A | 1983-05-02 | 1983-05-02 | |
| US490,819 | 1983-05-02 | ||
| US49194983A | 1983-05-05 | 1983-05-05 | |
| US491,949 | 1983-05-05 | ||
| US55749283A | 1983-12-02 | 1983-12-02 | |
| US557,492 | 1983-12-02 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1205077A true CA1205077A (en) | 1986-05-27 |
Family
ID=27504226
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000450478A Expired CA1205077A (en) | 1983-03-28 | 1984-03-26 | Herbicidally active 3-isoxazolyl-2-imidazolidinone derivatives |
Country Status (3)
| Country | Link |
|---|---|
| CA (1) | CA1205077A (en) |
| FR (1) | FR2543552B1 (en) |
| IT (1) | IT1178919B (en) |
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015193202A1 (en) * | 2014-06-16 | 2015-12-23 | Syngenta Participations Ag | Herbicidal compounds |
| CN105873918A (en) * | 2013-12-23 | 2016-08-17 | 先正达参股股份有限公司 | Dihydro-hydantoin derivatives with herbicidal activity |
| WO2016162265A1 (en) * | 2015-04-07 | 2016-10-13 | Syngenta Participations Ag | Herbicidal mixtures |
| WO2018015476A1 (en) | 2016-07-22 | 2018-01-25 | Syngenta Participations Ag | Method of controlling plants |
| WO2018065311A1 (en) | 2016-10-07 | 2018-04-12 | Syngenta Participations Ag | Herbicidal mixtures |
| WO2018065309A1 (en) | 2016-10-07 | 2018-04-12 | Syngenta Participations Ag | Herbicidal mixtures |
| WO2020161147A1 (en) | 2019-02-05 | 2020-08-13 | Syngenta Crop Protection Ag | Herbicidal mixtures |
| WO2020164925A1 (en) | 2019-02-15 | 2020-08-20 | Syngenta Crop Protection Ag | Herbicidal compositions |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4659836A (en) * | 1985-06-10 | 1987-04-21 | Ppg Industries, Inc. | Imidazolidinone imines |
| AU581763B2 (en) * | 1985-06-14 | 1989-03-02 | Ppg Industries, Inc. | Herbicidal imidazolidinone derivatives |
| US4707180A (en) * | 1985-06-14 | 1987-11-17 | Ppg Industries, Inc. | Herbicidally active isoxazolyl-imidazolidinone derivatives |
| US4756744A (en) * | 1985-06-24 | 1988-07-12 | Ppg Industries, Inc. | Herbicidally active 4-aminoalkylamino-3-isoxazolyl-2-imidazolidinone derivatives |
| US5484763A (en) * | 1995-02-10 | 1996-01-16 | American Cyanamid Company | Substituted benzisoxazole and benzisothiazole herbicidal agents |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NZ197589A (en) * | 1980-07-07 | 1984-11-09 | Lilly Co Eli | 3-(isoxazol-3 or 5-yl)-4 hydroxyimidazolidin-2-ones and corresponding imidazolin-2-ones |
| US4354030A (en) * | 1981-12-24 | 1982-10-12 | Eli Lilly And Company | Isoxazolylimidazolidinone herbicides |
-
1984
- 1984-03-26 CA CA000450478A patent/CA1205077A/en not_active Expired
- 1984-03-27 IT IT67299/84A patent/IT1178919B/en active
- 1984-03-28 FR FR8404881A patent/FR2543552B1/en not_active Expired
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105873918A (en) * | 2013-12-23 | 2016-08-17 | 先正达参股股份有限公司 | Dihydro-hydantoin derivatives with herbicidal activity |
| WO2015193202A1 (en) * | 2014-06-16 | 2015-12-23 | Syngenta Participations Ag | Herbicidal compounds |
| WO2016162265A1 (en) * | 2015-04-07 | 2016-10-13 | Syngenta Participations Ag | Herbicidal mixtures |
| WO2018015476A1 (en) | 2016-07-22 | 2018-01-25 | Syngenta Participations Ag | Method of controlling plants |
| WO2018065311A1 (en) | 2016-10-07 | 2018-04-12 | Syngenta Participations Ag | Herbicidal mixtures |
| WO2018065309A1 (en) | 2016-10-07 | 2018-04-12 | Syngenta Participations Ag | Herbicidal mixtures |
| WO2020161147A1 (en) | 2019-02-05 | 2020-08-13 | Syngenta Crop Protection Ag | Herbicidal mixtures |
| WO2020164925A1 (en) | 2019-02-15 | 2020-08-20 | Syngenta Crop Protection Ag | Herbicidal compositions |
Also Published As
| Publication number | Publication date |
|---|---|
| IT8467299A1 (en) | 1985-09-27 |
| FR2543552A1 (en) | 1984-10-05 |
| IT1178919B (en) | 1987-09-16 |
| FR2543552B1 (en) | 1986-07-25 |
| IT8467299A0 (en) | 1984-03-27 |
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