CA1255317A - Herbicidal 2-(oxa or thia heterocycle)5-amino-3-oxo-4- (substituted-phenyl)-2,3-dihydrofurans - Google Patents
Herbicidal 2-(oxa or thia heterocycle)5-amino-3-oxo-4- (substituted-phenyl)-2,3-dihydrofuransInfo
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- CA1255317A CA1255317A CA000489238A CA489238A CA1255317A CA 1255317 A CA1255317 A CA 1255317A CA 000489238 A CA000489238 A CA 000489238A CA 489238 A CA489238 A CA 489238A CA 1255317 A CA1255317 A CA 1255317A
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Abstract
ABSTRACT OF THE DISCLOSURE
The invention relates to herbicidal 2-(oxahetero-cycle or thiaheterocycle)-5-amino-3-oxo-4-(substituted-phenyl)-2, 3-dihydrofurans of the formula
The invention relates to herbicidal 2-(oxahetero-cycle or thiaheterocycle)-5-amino-3-oxo-4-(substituted-phenyl)-2, 3-dihydrofurans of the formula
Description
~s;~t7 ~IERBICIDAL 2-(OXA OR THIA IIETEROCYCLE)5-AMINO-3-OX0-4-~SUBSTITUTED-PHENYL)-2,3-DIHYDROFURANS
BACKGROUND OF THE INVENTInN
This invention relates to 2-(oxa and thia hetero-cycle) 5-amino-3-oxo-4-(substituted-phenyl)-2,3-dihydrofurans and derivatives thereof and to the use o-f such compounds as herbi-cides and plant growth regulators.
Chemiker-Zeitung 104 (1980) No. 10, Pages 302-303, is an academic paper disclosing the ring closure of l-(dimethyl-amino)-2,4-diphenyl-1-buten-3,4-dione to yield 5-dimethylamino-
BACKGROUND OF THE INVENTInN
This invention relates to 2-(oxa and thia hetero-cycle) 5-amino-3-oxo-4-(substituted-phenyl)-2,3-dihydrofurans and derivatives thereof and to the use o-f such compounds as herbi-cides and plant growth regulators.
Chemiker-Zeitung 104 (1980) No. 10, Pages 302-303, is an academic paper disclosing the ring closure of l-(dimethyl-amino)-2,4-diphenyl-1-buten-3,4-dione to yield 5-dimethylamino-
2,4-diphenyl-2,3-dihydrofuran. British Patent No. 1,521,092, discloses certain 3-phenyl-5-substituted-4(1H)-pyrid-ones or -~hiones as herbicides. Japanese Patent Application 13,710/69 (Chemical Abstracts 71:61195e) discloses 5-amino-3-oxo-4-(phenyl or 4-chlorophenyl)-2,3-dihydrofurans. Japanese Patent No.
19090 (Chemical Abstracts 69P10352e) discloses certain 2,3-~; dihydrothiophenes as pharmaceuticals. Helvetica Chemica Acta, Volume 66, Pages 362-378 (1983) discloses 5-N-cyclopropyl-4-phenyl-2-methoxycarbonyl-methylene-3-furanone as part of an academic chemical synthesis discussion.
In my Belgian Pa~ent No. 899,931 issued December 17, 1984, I disclosed certain 2-aryl 5-amino-3-oxo-4-(substituted phenyl)-2,3-dihydrofuran derivatives and their use as herbicides.
SUMMARY OF THE INVENTION
The present invention provides compounds having both pre-emergence and post-emergence herbicidal activity and having `~ especially good pre-emergence activity against a broad spectrum of both broad-leaf weeds and grassy weeds. At lower application rates the compounds also exhibit plant growth regulating properties.
The compounds of the present invention can be re-presented by the following formula:
,':;, ~ :' :
01 --2~
05 R4 J~D
R ~ ~
~I) wherein Rl and R2 are independen~ly hydrogen, lower alkyl, having 1 through 4 carbon atoms, or alkenyl having 3 through 6 carbon atoms;
R3 is hydrogen, lower alkyl, lower alkoxy, halo, or trifluoromethyl; R4 is lower alkyl, lower alkoxy, halo, or trifluoromethyl;
Z is a saturated or unsaturated heterocycle radical having five or six ring atoms includiny one or two oxygen or sulfur atoms and the remainder are carbon atoms.
The invention also comprises compatible salts of the com-pound of Formula (I~.
The compounds exist as keto-enol tautomer isomers with respect to the 3-keto group shown in Formula I. Also, where tne compounds of Formula (I) have an asym-metric carbon atom they can exist as optical isomers. The above formula is intended to encompass both the respective tautomers and optical and geometric isomers where they exist as well as mixtures thereof and the respective isomers as well as mixtures thereof are encompassed within the invention.
It has also been discovered that the presence of a 3-trifluoromethyl substituent on the 4-phenyl group of the compounds of the present invention generally very substantially enhances herbicidal activity.
~ In a further aspect the invention provides a `~ herbicidal composition comprising a compatible carrier and a herbicidally effective amount of the compounds of ~0 L ?~
~1 -3-Formula (I~, or oanpatible sal~s thereof, or mixtures thereof.
05 The present invention also provides a method for preventing or controlling the growth of unwanted vegeta-tion, which comprises treating the growth medium and/or the foliaye of such vegetation with a herbicidally effec-tive amount of the compound(s) of Formula ~1) and/or com-patible salts thereof.
In another aspect, the present invention pro-vides a plant growth regulating composition comprising a compatible carrier and a plant growth regulating amount of the compound of Formula (I), compatible salts of Formula (I)~ or mixtures thereof, effective to alter the normal growth pattern of said plants.
The present in~ention also provides a method for regulating plant growth ~hich comprises treating the growth medium and/or ~he foliage of such vegetation with a plant growth regulating effective amount o~ the com-pound(s) of Formula (I) and/or compatible salts thereof, effective to alter ~he normal growth pattern of said plants.
The present invention al50 provides chemical intermediates and processes for prsparing the compounds of Formula ~I).
The invention will be further described herein-below.
~ FURTHER DESC~IPTION OF THE
-~ Illustrations of typical compounds of Formula (I) of the present invention can be had by refer-encs to Examples 3-7 s~t forth hereinbelow on Pages 14~23.
In terms of substituents, the preferred compounds are those wherein Rl and R2 are independently hydrogen, methyl, ethyl or n-propyl, and more preferably one of Rl ;~ or R2 is hydrogen and the other i5 hydrogen, methyl, ethyl or n-propyl, preferably methyl or ethyl. Preferably, R3 is hydrogen and R4 is trifluoromethyl or halo, ~; .
`:
~ .
19090 (Chemical Abstracts 69P10352e) discloses certain 2,3-~; dihydrothiophenes as pharmaceuticals. Helvetica Chemica Acta, Volume 66, Pages 362-378 (1983) discloses 5-N-cyclopropyl-4-phenyl-2-methoxycarbonyl-methylene-3-furanone as part of an academic chemical synthesis discussion.
In my Belgian Pa~ent No. 899,931 issued December 17, 1984, I disclosed certain 2-aryl 5-amino-3-oxo-4-(substituted phenyl)-2,3-dihydrofuran derivatives and their use as herbicides.
SUMMARY OF THE INVENTION
The present invention provides compounds having both pre-emergence and post-emergence herbicidal activity and having `~ especially good pre-emergence activity against a broad spectrum of both broad-leaf weeds and grassy weeds. At lower application rates the compounds also exhibit plant growth regulating properties.
The compounds of the present invention can be re-presented by the following formula:
,':;, ~ :' :
01 --2~
05 R4 J~D
R ~ ~
~I) wherein Rl and R2 are independen~ly hydrogen, lower alkyl, having 1 through 4 carbon atoms, or alkenyl having 3 through 6 carbon atoms;
R3 is hydrogen, lower alkyl, lower alkoxy, halo, or trifluoromethyl; R4 is lower alkyl, lower alkoxy, halo, or trifluoromethyl;
Z is a saturated or unsaturated heterocycle radical having five or six ring atoms includiny one or two oxygen or sulfur atoms and the remainder are carbon atoms.
The invention also comprises compatible salts of the com-pound of Formula (I~.
The compounds exist as keto-enol tautomer isomers with respect to the 3-keto group shown in Formula I. Also, where tne compounds of Formula (I) have an asym-metric carbon atom they can exist as optical isomers. The above formula is intended to encompass both the respective tautomers and optical and geometric isomers where they exist as well as mixtures thereof and the respective isomers as well as mixtures thereof are encompassed within the invention.
It has also been discovered that the presence of a 3-trifluoromethyl substituent on the 4-phenyl group of the compounds of the present invention generally very substantially enhances herbicidal activity.
~ In a further aspect the invention provides a `~ herbicidal composition comprising a compatible carrier and a herbicidally effective amount of the compounds of ~0 L ?~
~1 -3-Formula (I~, or oanpatible sal~s thereof, or mixtures thereof.
05 The present invention also provides a method for preventing or controlling the growth of unwanted vegeta-tion, which comprises treating the growth medium and/or the foliaye of such vegetation with a herbicidally effec-tive amount of the compound(s) of Formula ~1) and/or com-patible salts thereof.
In another aspect, the present invention pro-vides a plant growth regulating composition comprising a compatible carrier and a plant growth regulating amount of the compound of Formula (I), compatible salts of Formula (I)~ or mixtures thereof, effective to alter the normal growth pattern of said plants.
The present in~ention also provides a method for regulating plant growth ~hich comprises treating the growth medium and/or ~he foliage of such vegetation with a plant growth regulating effective amount o~ the com-pound(s) of Formula (I) and/or compatible salts thereof, effective to alter ~he normal growth pattern of said plants.
The present invention al50 provides chemical intermediates and processes for prsparing the compounds of Formula ~I).
The invention will be further described herein-below.
~ FURTHER DESC~IPTION OF THE
-~ Illustrations of typical compounds of Formula (I) of the present invention can be had by refer-encs to Examples 3-7 s~t forth hereinbelow on Pages 14~23.
In terms of substituents, the preferred compounds are those wherein Rl and R2 are independently hydrogen, methyl, ethyl or n-propyl, and more preferably one of Rl ;~ or R2 is hydrogen and the other i5 hydrogen, methyl, ethyl or n-propyl, preferably methyl or ethyl. Preferably, R3 is hydrogen and R4 is trifluoromethyl or halo, ~; .
`:
~ .
3~
Ol _4_ especially trifluoromethyl~ When Rl and/or R~ is alkenyl, preferably the alkenyl group has 3 or 4 carbon atoms.
The Z heterocycle group can be represented by the formulas:
X~Xl X..,X
~ J and ~ ~
wherein one or two of X, Xl, x2 or X3 are indepen-dently sulfur (divalent sulfur) or oxygen and the remain-der is carbon atoms and the inner ring dotted lines indicate that the ring can be saturated, unsaturated or partially saturated. The preferred Z heterocyclic groups are thiophene, furan, pyran and thiopyran.
The compounds of the invention wherein Rl and R2 are each hydrogen can be prepared by the following schema-tically represented process:
~) -CH2CN + Z-C-C-ORS - > R ~ + RSOH
R4 H ~2N
wherein R3, R4, and Z are as defined herein-above; and R5 i5 lower alkyl, aryl (e.g., phenyl) or arylalkylene (e.g., benzyl).
This process can be conveniently effected by contacting Compound (B) with Compound (~), and a strong base (e.g., sodium methoxide, sodium ethoxide), preferably in an iner~ organic solvent.
Typically, this process is conducted at tempera-tures in the range of about from 0 to 100C, preferably 75 to 85C for about fr~m 5 to 3S hours, preferably 18 to 24 hours, using about from 1 to 10, preferably 1 to 1.2 moles of Compound ~A) per mole of Compound (B).
. ,. ~
~ 5-;
Suitable strong bases which can be used include 7 for example, alkali metal alkanolates, for example, sodium methoxide, sodium ethoxide, potassium ethoxide9 sodium hydride, potassium hydride, and the like. The ~trong base should preferably be one which does not yield water as a by-product in this reaction system.
Suitable inert solvents which can be used include, for example, lower alkanol~ (for example, methanol, ethanol, and propanol) tetrahydr~furan, dimethoxyethane, dioxane, and the like, and compatible mixtures thereof. Conveniently, the alkali metal alkanolate is prepared in situ by reacting an alkali metal with excess alkanol which in turn serves as solvent for the above reaction.
The starting materials of Formula tB) are generally known materials and can be prepared by known - procedures, or obvious modifications thereof (i.e., ~ub-2Q stitution of appropriate starting materials). The pre-paration of Compound (B) is for example described in Org~ Syn. Coll., Volume l, 107 (194l).
; The hydroxy esters of Formula (A) are also generally known compounds and can be prepared by known ;~ 25 procedures or by obvious modifications thereof (e.g., hy using appropriately substituted starting materials). For example, via the reaction of the corresponding hetero-cycle-hydroxyacetonitrile with hydrogen chloride in methanol to yield the corresponding (2-imino-2-methoxy-l-hydroxyethyl)heterocycle hydrochloride salt which in turn can be hydrolyzed to the corresponding ester of formula ~ A. The initial heterocycle-hydroxyacetonitrile starting - material can be prepared via the reaction of the corre-sponding formyl heterocycle with sodium cyanide.
The compound of Formula (I) wherein one or bo~h of Rl and R2 are lower alkyl or lower alkenyl can be pre-pared by alkylation ~or alkenylation) of the amino group:
:~ `
. ,~
L'7 ~f ~ R6X _ ~
(I') (I'') wherein R3, R4 and Z are as defined hereinabove;
R6 is lower alkyl or lower alkenyl; R7 is hydrogen or R6; and R6X' is an alkylàtion or alkenylation agent.
This process can be effected by contacting Compound (I ' ) with a suitable alkylation or alkenylation agent capable of alkylating or alkenyla~ing primary or ~-~ secondary amino groups, ;~ For example, this can be effected by contacting 20 Compound (I' ) with a lower alkyl iodide or lower alkenyl iodide, preferably in an inert organic solvent and prefer-ably in the presence of a scavenger base. Typically, this process is conducted at temperatures in the range of about from 0 to 100C, preferably 20 to 45C for about from 25 1.0 ~o 72.0, preferably 2.0 ~o 18.0 hours. Where it is desired to alkylate or alkenylate only at R6, then typi-cally about from 1~0 to 1~1 moles of R~I reactant is used ,~
per mole of CompGund (I'). Where it is desired to alkyl-ate both amino hydrogens, then typically about from 1.9 to ~; 30 4.0 moles of R6l are used per mole of Compound (I'). Also variation in R6 and R7 can be effected by first alkylation of only one of ~he two amino hydrogens and then alkylating the second amino hydrogen with an alkylating ayent havin~
a different R6 alkyl or alkenyl group. Suitable inert 35 organic solvents which can be used, include~ for example, ., liquid halogenated alkanes; for example, methylene chloride, carbon tetrachloride, dichloroethane; tetra-~ hydrofuran and the like. ~uitable scavenger bases ; includei for example, the bases described hereinabove with
Ol _4_ especially trifluoromethyl~ When Rl and/or R~ is alkenyl, preferably the alkenyl group has 3 or 4 carbon atoms.
The Z heterocycle group can be represented by the formulas:
X~Xl X..,X
~ J and ~ ~
wherein one or two of X, Xl, x2 or X3 are indepen-dently sulfur (divalent sulfur) or oxygen and the remain-der is carbon atoms and the inner ring dotted lines indicate that the ring can be saturated, unsaturated or partially saturated. The preferred Z heterocyclic groups are thiophene, furan, pyran and thiopyran.
The compounds of the invention wherein Rl and R2 are each hydrogen can be prepared by the following schema-tically represented process:
~) -CH2CN + Z-C-C-ORS - > R ~ + RSOH
R4 H ~2N
wherein R3, R4, and Z are as defined herein-above; and R5 i5 lower alkyl, aryl (e.g., phenyl) or arylalkylene (e.g., benzyl).
This process can be conveniently effected by contacting Compound (B) with Compound (~), and a strong base (e.g., sodium methoxide, sodium ethoxide), preferably in an iner~ organic solvent.
Typically, this process is conducted at tempera-tures in the range of about from 0 to 100C, preferably 75 to 85C for about fr~m 5 to 3S hours, preferably 18 to 24 hours, using about from 1 to 10, preferably 1 to 1.2 moles of Compound ~A) per mole of Compound (B).
. ,. ~
~ 5-;
Suitable strong bases which can be used include 7 for example, alkali metal alkanolates, for example, sodium methoxide, sodium ethoxide, potassium ethoxide9 sodium hydride, potassium hydride, and the like. The ~trong base should preferably be one which does not yield water as a by-product in this reaction system.
Suitable inert solvents which can be used include, for example, lower alkanol~ (for example, methanol, ethanol, and propanol) tetrahydr~furan, dimethoxyethane, dioxane, and the like, and compatible mixtures thereof. Conveniently, the alkali metal alkanolate is prepared in situ by reacting an alkali metal with excess alkanol which in turn serves as solvent for the above reaction.
The starting materials of Formula tB) are generally known materials and can be prepared by known - procedures, or obvious modifications thereof (i.e., ~ub-2Q stitution of appropriate starting materials). The pre-paration of Compound (B) is for example described in Org~ Syn. Coll., Volume l, 107 (194l).
; The hydroxy esters of Formula (A) are also generally known compounds and can be prepared by known ;~ 25 procedures or by obvious modifications thereof (e.g., hy using appropriately substituted starting materials). For example, via the reaction of the corresponding hetero-cycle-hydroxyacetonitrile with hydrogen chloride in methanol to yield the corresponding (2-imino-2-methoxy-l-hydroxyethyl)heterocycle hydrochloride salt which in turn can be hydrolyzed to the corresponding ester of formula ~ A. The initial heterocycle-hydroxyacetonitrile starting - material can be prepared via the reaction of the corre-sponding formyl heterocycle with sodium cyanide.
The compound of Formula (I) wherein one or bo~h of Rl and R2 are lower alkyl or lower alkenyl can be pre-pared by alkylation ~or alkenylation) of the amino group:
:~ `
. ,~
L'7 ~f ~ R6X _ ~
(I') (I'') wherein R3, R4 and Z are as defined hereinabove;
R6 is lower alkyl or lower alkenyl; R7 is hydrogen or R6; and R6X' is an alkylàtion or alkenylation agent.
This process can be effected by contacting Compound (I ' ) with a suitable alkylation or alkenylation agent capable of alkylating or alkenyla~ing primary or ~-~ secondary amino groups, ;~ For example, this can be effected by contacting 20 Compound (I' ) with a lower alkyl iodide or lower alkenyl iodide, preferably in an inert organic solvent and prefer-ably in the presence of a scavenger base. Typically, this process is conducted at temperatures in the range of about from 0 to 100C, preferably 20 to 45C for about from 25 1.0 ~o 72.0, preferably 2.0 ~o 18.0 hours. Where it is desired to alkylate or alkenylate only at R6, then typi-cally about from 1~0 to 1~1 moles of R~I reactant is used ,~
per mole of CompGund (I'). Where it is desired to alkyl-ate both amino hydrogens, then typically about from 1.9 to ~; 30 4.0 moles of R6l are used per mole of Compound (I'). Also variation in R6 and R7 can be effected by first alkylation of only one of ~he two amino hydrogens and then alkylating the second amino hydrogen with an alkylating ayent havin~
a different R6 alkyl or alkenyl group. Suitable inert 35 organic solvents which can be used, include~ for example, ., liquid halogenated alkanes; for example, methylene chloride, carbon tetrachloride, dichloroethane; tetra-~ hydrofuran and the like. ~uitable scavenger bases ; includei for example, the bases described hereinabove with
4~ respect to the reaction of Compound ~A) with Compound (B).
, .. .
, .. .
5~ 7 61936-16~5 The ~ompounds o~ Formula (I") ~7herein R is lower alkyl ~e.g., methyl) ancl ~7 is hydrogen or lower alkyl, can be advantageously prepared using dialkyl sulfate as the alkylating agent. This can be conveniently effected by contacting the compound of Formula (I') or II") with the desired lower alkyl sulfates in the presence of a strong base and preferably in an inert organic solvent in the presence of a phase transfer agent. Typically, this process is conducted at temperatures in the range of about frQm 0 to 100C, preferably 20 to 45C, using about from 1.0 to 4.0 moles of dialkyl sulfate per mole of Compound (I'). An excess, typically about 2.5 mole of base is used. Preferablyr this process is also conducted in an inert organic solvent such as, for example, methylene chloride, carbon tetrachloride, dichloroethane, tetrahydrofuran, and the like.
Suitable strong bases which can be used include, for example, sodium hydroxide, potassium hydroxide, sodium ethoxide, sodium carbonate, potassium carbona~e, and the like.
Suitable phase transfer agents are agents whi~h transfer hydrophilic ions into a lipophilic oryanic medium and include, for example, benzyl triethylammonium chloride, ~etra-n-butylammonium chloride, methyltrioctylammoni.um chloride, and ;~ the like.
The compatible salts of Formula (I) can be prepared by conventional procedures ky treating the compound of Formula ~I) wherein R1 andtor R2 is hydrogen with a suita~le strong base such as, for example, n-butyllithium, sodium hydride, potassium hydride, and the like, having the desired cation, by : 30 conventiollal procedures to replace an amine hydrogen wi~h the ~ ` ~ fl 7 . ~, .
~55~:~7 61g36-1665 desired carbon. The -three-position enolate salts can be prepared via further treatment of the amine salt with base.
Additional variati.ons in the salt cation can also be effected via ion exchange with an ion exchange resin having the desired cation.
General Process Conditions In the above-described processes, it is generally preferable to separate the respective products before 7a ,, ,~
~ . ~. /
. . , " '' ;
3:a7 Ol -8 proceeding with the next step in the reaction sequence, cxcept where described as an in situ step or unless other-05 wise expressly stated. These products can be recoveredfrom their respective reaction produet mixtures by any suitable separation and purification procedure, such as, for example, recrystallization and chromatography. Suit-able ~eparation and purification procedures are, for exam-~le, illu5tratsd in the Examples set forth hereinbelow.
Generally, the reactions described above areconducted as liquid phase reaction and hence pressure is generally not significant except as it affects temperature (boiling point) where reactions are conducted at reflux~
lS Therefore, these rcactions are generally conducted at pressures of about from 300 to 3,000 mm of mercury and ` conveniently are conducted at about atmospheric or ambient pressure~
It should also be appreciated that where typical or preferred process conditions (e.g., reaction tempera-tures, times, mole ratios of reactant~, solvents, etc.) have been given, that other process conditions could also be used. Optimum reaction conditions (e.g., temperature, reaction time, mol ratios, solvents, etc~ may vary with the particular reagents or organic solvents used but can be determined by routine optimization procedures.
Where optical isomer mixtures are obtained, the respective optical isomers can be obtained by conventional resolution procedures~ Geometric isomers can be scparated by conventional separation procedures which depend upon differences in physical properties between the geometric isomers.
~efinitions As used herein the following terms have the following meanings unless expressly stated ~o the contrary:
The term "lower alkyl" refers to both straight and branched-chain alkyl groups having a total of from 1 through ~ r pre~erably 1 through 4, carbon atoms and includes primary, secondary and tertiary alkyl groups.
;5~
61936-lG65 Typical lower alkyls include, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl.
The term "lower alkenyl" refers to alkenyl groups having 2 through 6, preferably 2 through 4, carbon atoms and includes, for example, vinyl, 1-propenyl, 2-propenyl, 1-methylvinyl, 1-butenyl, 2-methylprop-1-enyl and the like.
The term "halo" refers to the group of fluoro, chloro, bromo and iodo.
The term "aryl" refers to aryl groups having 6 through 10 carbon atoms and includes, for example, phenyl, naphthyl, indenyl, and the like.
The term "substituted aryl" refers to aryl groups having 1 through 3 substituents independently selected from the group of lower alkyl, lower alkoxy, halo, nitro, or haloalkyl having 1 throuyh 3 carbon atoms and 1 through 3 halo atoms.
Typical substituted aryl groups include, for example, 2-fluoro-phenyl, 2-chlorophenyl, 2,6-dimethylphenyl, 4-fluorophenyl, 2-methylphenyl, 2-chloro, 4-chloromethylphenyl, 2-nitro,5-methylphenyl, 2,4-dichlorophenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, and the like.
The term "arylalkylene" or "arylalkyl" refers to the group ArRS- wherein Ar is aryl and R5 is alkylene having 1 through 3 carbon atoms and includes both straight-chained and branched-chained alkylenes, for example, methylene, ethyl, 1-methylethyl, and propyl.
The term "~substituted aryl)alkylene" or "ring-substituted arylalkylene" refers to the group Ar'R5- wherein Ar' is substituted aryl and R5 is alkylene as defined with respect to arylalkylene.
.
The term "compatible salts" refers to salts which do not significantly alter the herbicidal properties of the parent compound. Suitable salts include cation salts su~h as, for example, the cation replacement salts of lithium, sodium, potassium, alkali earth metals, ammonia, quaternary ammonium salts, and the like.
9a S3~7 The term ~room temperature" or ~ambient temper-ature" refers to about 20-25C.
~5 ~
The compounds of Formula (I) exhibit both pre-emergence and post-emergence herbicidal activity and exhibit especially good pre-emergence herbicidal activity.
Generally, for post-emergent applications, the herbicidal compounds are applied directly to the foliage or other plant parts. For pre-emergence applications, the herbicidal compounds are applied to the growth medium, or prospective growth medium, for the plant. The optimum amount of the herbicidal compound or composition will vary with the particular plant species, and the extent of plant growth, if any, and the particular part of the plant which is contacted and the extent of contact. The optimum dosage can also vary with the general location, or i environment (e.g., shelter~d areas such as greenhouses ~; 20 compared to exposed areas such as fields), and type and ~ degree of control desired. Generally, for both pre- and ;~ post-~mergen~ con~rol, the present compounds are applied at rates of about from 0~02 to 60 kg/ha, preferably about from 0.02 to lO kg/ha.
;~ 25 Also, although in theory the compounds can be applied undiluted, in actual practice they are generally applied as a composition or formulation comprising an effective amount of the compound(s) and an acceptable car-rier. An acceptable or compatible carrier (agriculturally acceptable carrier) is one which does not significantly adversely affect the desired biological effect achieved by the active compounds, save to dilute it. Typically, the composition contains about from 0~05 to 95% by weight of the compound of Formula (I) or mixtures thereof . Concen-trates can also be made having high concentrations designed for dilution prior to application, The carrier can be a solid, liquid, or aerosol. The actual com~osi-tions can take the form of granules, powders, dusts, solu-tions, emulsions, slurries, aerosols, and the like.
5~7 Suitable solid carriers which can be used include, for example, natural clays ~such a kaolin, 05 ~ttapulgite, montmorillonite, etc.), talcs, pyrophyllite, diatomaceous silica, synthetic fine silica, calcium alumi-nosilicate, tricalcium phosphate, and the like. Also, organic materials, such as, for example, walnut shell flour, cotton-seed hulls, wheat flour, wood flour, wood bark flour, and the like can also be used as carriers.
Suitable liquid diluents which can be used include, for example, water, organic solvents (e.g., hydrocarbons such as benzene, toluene, dimethylsulfoxide, kerosene, diesel fuel, fuel oil, petroleum naphtha, e~c.), and the like.
Suitable aerosol carriers which can be used include con-ventional aerosol carriers such as halogenated alkanes, etc.
The composition can also contain various promo-ters and surface-active agents which enhance the rate of transport of the active compound into the plant tissue such as, for example, organic solvents, wetting agents and oils, and in the case of compositions designed for pre-emergence application agents which reduce the leachability of the compound or otherwise enhance soil stability.
The composition can also contain various com-patible adjuvants, stabilizers, conditioners, insecti-cides, fungicides, and if desired, other herbicidally ~; active compounds.
At reduced dosages the compounds of the present invention also exhibit plant growth regulating activity and can be used to alter the normal growth pattern of green plants.
The compounds of Formula (I) can be applied as plant growth regula~ors in pure form, but more pragmatic-ally/ as in the case of herbicidal application, are applied in combination with a carrier. The same types of carriers as set forth hereinabove with respect to the herbicidal compositions can also be used. Depending on the desired application, the plant growth re~ulating com-;~ 40 position can also contain, or be applied in combination ~S~i3~
l2-with other compatible ingredien~s such as desiccants, defoliants, surace-active a~ents, adjuvants, fungicides, 05 and insecticides. Typically, the plant gr~wth regulating composition will contain a total of about from 0.005 to 90 wt. % of the compound(s) of Formula (I~ depending on whether the composition is intended to be applied directly or diluted first.
A further understanding of the invention can be had in the following non-limiting Preparation and Examples. Wherein, unless expressly stated to the con-trary, all temperatures and temperature ranges refer to the Centigrade system and the term Nambient" or Uroom temperature" refers to about 20-25C. The term "percent"
or ~" refers to weight percent and the tenm "mole" or moles~ refers to ~ram moles. ~he term "equivalent"
refers to a quantity of reayent equal in moles, to the ~ moles of the precedin~ or succeeding reactant rscited in `~ 20 that example in terms of finite moles or finite weight or volume. Where given, proton-magnetic resonance spectrum ;~ (p.m.r. or n.m.r.) were determined at 60 mHz, signals are assigned as singlets (s), broad singlets (bs), doublets (d), double doublets (dd), triplets ~t), double triplets (dt), quartets (q~, and multiplets (m); and cps refers to cycles per second. Also where necessary, examples are repeated to provide additional starting material for sub-sequent examples.
EXA~PLES
3C Example l . ~
In this example 25.0 y of 2-formylthiophene was added to a stirred solution containing lO.93 9 of sodium cyanide in 37 ml of water at room temperature. 63 ml of 3S aqueous satura~ed sodium acid sulfite was then slowly added to the stirred mixture. During the addition of the ; sodium acid ~ulfite solution, small amounts (about 20 9) of ice were periodically added The mixture was then s~irred for another l~ minutes and extracted with ethyl e~her. The ethyl ether extracts were combined, dried over , 53~'7 magnesium sulfate and evaporated under vacuum affording 18.4 g of the title compound.
~xample 2 Methyl T ~
(a) In this example 6.8 9 of methanol was added to a stirred solution of 26.9 9 of thienyl-2-yl-hydroxy-acetonitrile in 100 ml ethyl ether at about 10C~ Hydro-gen chloride was then bubbled through this mixture until the formation of a salt precipitate was observed. The mixture was then stirred for about 15 minutes at about 10C and then filtered. The filter cake was washed with ethyl ether and then evaporated affording 18.2 g of the chloride salt of 2-(2-imino-2-methoxy-1-hydroxyethyl)thio-phene.
(b) The above salt was then dissolved in water and stirred at room tempera~ure for about 30 minutes and then extracted three ~imes with ethyl ether.
The ethyl ether extracts were combined, dried over magnesium sulfate and concentrated by evaporation under vacuum, affording 8.3 9 of the title compound.
The filtrate from step (a) was allowed to stand overnight (about 16-18 hours) at room temperature and was then filtered. The filter cake was treated as before affording an additional 11.7 g of chloride salt. This salt was then hydrolyzed with water as described above affording an additional 4~4 g of the title compound.
Similarly, by applying the procedures of Examples 1 and 2 using the a~propriate heterocyclic-hydroxyacetonitrile star~ing material~ in Example 1, the following compounds can be prepared.
Methyl thien-3-yl-hydroxyacetate;
Methyl(2,3 dihydrothien 2-yl~-hydroxyacetat~
Methyl tetrahydrothien-3-yl-hydroxyacetate;
Methyl(2H-thiopyran-2-yl)-hydroxyacetate Methyl fur-2-yl-hydroxyacetate;
Methyl fur-3-yl-hydroxyacetate;
Methyl(2,3-dihydrofur-2-yl)-hydroxyacetate;
Methyl tetrahydrofur-3-yl hydroxyacetate;
~X~
Methyl~4H-pyran-2-yl) hydroxyacetate;
Methyl(2H 3,4-dihydropyran-3 yl)-hydroxyacetate; and 05 Methyl(tetrahydropyran-2-yl)-hydroxyacetateO
Example 3 2-Thien-2-yl-3-oxo-4-(3-trifluoromethylphenyl)-5-amino-2 3-dihvdrofuran A dry, 250-ml, three-neck, round-bottom flask equipped with a mechanical stirrer, addition funnel and a reflux condenser bearing a nitrogen inlet tube was charged ~ with 4.2 ~ of sodium and lO0 ml of absolute ethanol. To i~ the resulting sodium ethoxide solution was added dropwise ~ a mixture of 21 o l g Of methyl thien-2-yl hydroxyacetate ;~ 15 and 22.7 g of m-trifluoromethylphenyl-acetonitrile in 20 ml of ethanol. The resulting mixture was heated at reflux for 4-5 hours after which time it was added to 300-400 ml of water and extracted with petroleum ether.
The aqueous phase was acidified with aqueous lO weiyht percent hydrochloric acid and extracted two times with diethyl ether. The ether extracts were washed twice wi~h ~; saturated aqueous sodium bicarbonate, dried over magnesium sulfate and concentrated in vacuo to yield a thick dark oil~ This oil was triturated with 20-30~ ether/petroleum ether which afforded 4.9 9 of the ~itle compound as a tan powder.
Similarly, by applying the above-described pro-cedure using the appropriate (substituted phenyl) aceto-nitrile starting materials the following eompounds can also be prepared:
2-(thien-2-yl)-3-oxo-4-~5-ehloro-3-trifluoromethyl-phenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(4-chloro-3-~rifluoromethyl-phenyl)-5-amino-2,3 dihydrofuran;
2-(thien-2-yl)~3-oxo-4-(2-bromo-3-trifluoromethyl-~` phenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-[6-fluoro--3 trifluoromethyl-phenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(4 methyl-3-trifluoromethyl-phenyl)-5-amino 2,3 dihydrofuran;
.~
~53~7 2-(thien-2 yl)-3-oxo-4-(5-methoxy-3-trifluoromethyl-phenyl)~5-amino-2,3 dihydrofuran;
05 2-(thien-2-yl)-3-oxo-4-(6-isopropyl-3-trifluoro-methylphenyl)-5-amino-2,3-dihydrofuran 2-(thien-2-yl)-3-oxo-4-(3,5-di-trifluoromethylphenyl~-5-amino-2,3-dihydrofuran;
2-(thien-2-yl) 3-oxo-4-(3-propylphenyl)-5-amino-2,3-dihydrofuran;
2-~thien-2-yl)-3-oxo-4-(3-methylphenyl)-S-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-fluorophenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-methoxy~henyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-iodophenyl)-5-amino-2,3-dihydrofuran; and 2-(thien-2-yl)-3-oxo-4-(2-chloro-3-methylphenyl)-5-amino-2,3-dihydrofuran;
2-~thien-2-yl)-3-oxo-4-(4-ethyl-3-methylphenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-~5-methoxy-3-chlorophenyl)-5-amino-2,3-~ihydrofuran;
2-(thien-2-yl)-3-oxo-4-(6-ethoxy-3-chlorophenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3~oxo~4-(3,5-diethoxyphenyl)-5-amino-2,3-dihydrofuran;
~: 2-(thien-2-yl)-3-oxo-4-(3-brsmophenyl)-5-amino-2,3-; 30 dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-chloro-4-methylphenyl)-S-~ amino-2,3-dihydrofuran;
: 2-(thien-2-yl)-3-oxo-4-(3-bromo-2-ethylphenyl)-S-amino-2,3-dihydrofuran;
2-~thien-2-yl)-3-oxo-4-(3,6-dimethylphenyl)-5-amino-2,3--dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-iodo-4-methylphenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-chlorophenyl)-5-amino-2,3-dihydrofuran;
.,, ~l~2S53~7 2-(thien-2-yl)-3-oxo-4-~3-butylphenyl)-5-amino-2,3-dihydrofuran;
05 2-(thien-2-yl)-3-oxo-4-(3-butoxyphenyl)-5-amino-2,3-dihydrofuran; and 2-~thien-2-yl)-3-oxo-4-(3-isvpropoxyphenyl)-5-amino-2,3-dihydrofuran.
Similarly by applying the above procedure using the appropriate (substituted phenyl)acetonitrile and the appropriate methyl heterocycle-hydroxyacetate compound of the list given in Example 2 the corresponding 2~hetero-cycle analogs of the a~ove compounds can also be prepared for example:
;~ 2-~thien-3-yl)-3-oxo-4-(3-bromophenyl)-5-amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-t3-iodophenyl)-5 amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-propylphenyl)-5-amino-2,3-2U dihydrofuran;
2-(thien~3-yl~-3-oxo-4-(3-methoxyphenyl) 5-amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-fluorophenyl)-5-amino-2,3-dihydrofuran; and ~5 2-(thien-3-yl)-3-oxo-4-(3-propoxyphenyl)-5-amino-2,3-dihydrofuran.
2-(thien-3-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-chlorophenyl)-5-amino-2,3-~ 30 dihydrofuran;
- 2-(2,3-dihydrothien-2-yl)-3-oxo-4-(3-trifluoromethyl-: phenyl)-5-amino-2,3-dihydrofuran;
2-(2,3-dihydrothien-2-yl)-3-oxo-4-(3,5-diethoxy-~ phenyl)-5-amino-2,3-dihydrofuran;
~ 2-(tetrahydrothien-3-yl)-3-oxo-4-~3-trifluoromethyl-phenyl)-5-amino-2,3-dihydrofuran;
2-(?H-thiopyran-2-yl)-3-oxo-4-(3-bromophenyl)-5-amino-2,3-dihydrofuran;
2-(2H-thiopyran-2-yl)-3-oxo-4-(2-chloro-3-trifluoro-methylphenyl)-5-amino-2,3-dihydrofuran, ~S~3~'7 2-~fur-~-yl)-3 oxo-4-t3-trifluoromethyl-5-chloro-phenyl)-5-amino-2,3-dihydrofuran;
05 2-(fur-2-yl)-3-oxo-4-(3-fluorophenyl)-5-amino-2,3-dihydrofuran;
2-(fur-2-yl)-3~oxo-4-(3-bromophenyl)-5-amino-2,3-dihydrofuran;
2-(fur-2-yl)-3-oxo-4-(3-chlorophenyl)-S-amino-2,3-dihydrofuran;
2-(fur-2 yl)-3-oxo-4-(3-methylphenyl~-5-amino-2/3~
dihydrofuran;
2-(ur-2-yl)-3-oxo 4-(2-butoxy-3-trifluoromethyl-phenyl)-5-amino-2,3-dihydrofuran;
2-(fur-2-yl)~3-oxo-4-(3-trifluoromethylphenyl~-5-amino-2,3-dihydrofuran;
2-(fur-2-yl)-3-oxo-4-(3-iodophenyl)-5-amino-2,3-dihydrofuran;
2-(fur-2-yl~-3-oxo-4-(3-pro~ylphenyl)-S-amino-2,3-dihydrofuran;
2-(2,3-dihydrofur-2-yl)-3-oxo-4-(3-trifluoromethyl-~ phenyl)-5-amino-2,3-dihydrofuran;
`~ 2-(2,3-dihydrofur-2-yl)-3-oxo-4-(2-bromo-3-trifluoro-methylphenyl)-5-amino-2,3-dihydrofuran;
2-(tetrahydrofur-2-yl)-3-oxo-4-(3-trifluoromethyl-. phenyl)-5-amino-2,3-dihydrofuran;
2-(tetrahydrofur-2-yl)-3-oxo-4-(4-me~hyl-3-tri~luoro-methylphenyl)-5-amino-2,3-dihydrofuran;
~ 2-(fur-3-yl)-3-oxo-4-(5-chloro-3-trifluoromethyl-:: 30 phenyl~5-amino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-fluorophenyl)-S-amino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-bromophenyl)-5-amino-2/3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-chlorophenyl)-S-amino-2,3-dihydrofuran;
2~fur-3-yl)-3-oxo-4-(3-methylphenyl)-5-amino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(2-butoxy-3-~rifluoromethyl-p~enyl)-5-amino-2,3-dihydrofuran;
., ~2~53~
~1 -18-2-~ur-3-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-amino-2,3-dihydrofuran;
05 2- ( f ur-3-yl)-3-oxo-4-(3-methoxyphenyl)-5-amino-2,3-dihydrofuran;
2-lfur-3-yl)-3-oxo-4-(3-ethylphenyl)-5-amino-2,3-dihydrofuran;
2-~2,3-dihydrofur-2-yll-3-oxo-4-(3-trifluoromethyl-phenyl)-5-amino-2r3-dihydrofuran;
2-~2,3-dihydrofur-2-yl)-3-oxo-4-(2-bromo-3-trifluoro-methylphenyl)-5-amino-2,3-dihydrofuran;
2-(tetrahydrofur-3-yl)-3-oxo-4-(3-trifluoromethyl-phenyl)-5-amino-2,3-dihydrofuran;
~ 15 2-(tetrahydrofur-3-yl)-3-oxo-4-(4-methyl-3-trifluoro-: methylphenyl)-5-amino-2,3-dihydrofuran;
2 (4H-pyran-2-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-amino-2~3-dihydrofuran;
2-~4H-pyran-2-yl)-3-oxo-4-~3-fluorophenyl3-5-amino-2,3-dihydrofuran;
2-~4H-pyran-2-yl)-3-oxo-4-(3-methylphenyl)-5-amino-2,3-dihydrofuran;
2-(4H-pyran-2-yl)-3-oxo-4-(2-methyl-3-trifluoro-methylphenyl)-5-amino-2,3-dihydrofuran;
2-(4H-pyran-2-yl)~3-oxo-4-(2-nitro-3-methylphenyl)-5-amino-2 r3-dihydrofuran;
2-~2H-3,4-dihydropyran-3-yl)-3-oxo-4-(3-trifluoro-methylphenyl)-5-amino-2,3-dihydrofuran;
2-~2H-3,4-dihydropyran-3-yl~-3-oxo-4-~2-chloro-3-~: 30 trifluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-~-2H-3,4-dihydropyran-4-yl)-3-oxo-4-(3-fluoro-phenyl) 5-amino-2,3-dihydrofuran;
2-~2H-3,4-dihydropyran-3-yl)-3-oxo-4-(2-chloro-3-~: methylphenyl~-5-amino-2,3-dihydrofuran;
~ 2-(tetrahydropyran-2-yl)-3-oxo-4-(3-trifluoromethyl-~ phenyl)-5-amino-2~3-dihydrofuran;
:~ 2 tetrahydropyran-2-yl-3-oxo-4-(3-chloro-5-methyl-: phenyl)-5-amino-2,3-dihydrofuran;
2-( tetrahydropyran-2~yl ) -3 oxo-4- ( 3-fluorophenyl)-5-~ amino-2,3-dihydrofuran; and .~
~1936-1665 2-ltetrahydropyran-2-yl)-3-oxo-4-l3-ethylphenyl)-5-amino-~,3-dihydrofuran.
Example 4 2-Thien-2-yl-3-oxo-4-(3-trifluoromethylphenyl)-_ _ 5-methylamino-2~3-dihydrofuran In thi~ example about 0.36 g of ~olid sodium hydroxide was dissolved in a small amount oE water and then added to 100 ml of methylene ~hlorid~ containin~ 1.4 g of 2-thien-2-yl-3-oxo-4-(3-trifluoromethylphenyl)-5-amino-2,3-dihydrofuran. 0.20 g of benzyltriethylammonium ~hloride was added and then a mixture containing O.B4 ml of dimethyl sulfate in a~out 5.0 ml of methylene chloride was slowly added at room temperature. The mixture was stirred at room temperature for about one hour and then washed twice with water, twice with N. aqueous hydrochloric acid, twice with sodium bicarbonate, dried over magnesium sulfate and then concentra~ed by evaporation under vacuum. The residue was then triturated in a mixture of ethyl ekher and petroleum ether affording 1.4 g of the title compound.
Similarly, by following the ~ame procedure usiny the products listed ln Example 3 as starting materials, the corresponding 5-methylamino homoloys thereof can be prepared, for example:
2-(thien-2-yl)-3-oxo-4-(5-chloro-3-trifluoromethyl-phenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(4-chloro-3-tri~luoromethyl-phenyl)-5 methylamino-2,3-dihydrofuran;
2-l~hien-2-yl)-~-oxo-4-(2-bromo-3-triiluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-~6-fluoro-3-trifluoromethyl-phenyl)-5-methylamino-2,3-dihydrofuran;
~ 19 2-(~hien-2~yl)-3-oxo-4-(4-methyl~3-trifluoromethylphenyl)-5-methylamino-2,3~dihydrofuran;
2-(thien-2-yl)-3-oxo-4(5-methoxy-3-trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(6-isopropyl-3-trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
r l9a ~5~7 2-~thien-2-yl)-3-oxo-4-(3,5-di-trifluoromethyl-phenyl)-S-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-propylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-methylphenyl)~5-methylamino-2,3 dihydrofuran;
2-(thien-2-yl)~3-oxo-4-(3-fluorophenyl)-S-methyl-amino-2,3-dihydrofuran;
2 (thien-2-yl)-3-oxo-4-(3-methoxyphenyl)-5-methylam.ino-2~3-dihydrofuran;
2-(thien 2-yl)-3-oxo-4-(3-iodophenyl)-5-methylamino-2,3-dihydrofuran; and ~ lS 2-(thien-2-yl)-3-oxo-4-(2-chloro-3-methylphenyl~-5-: methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(4-ethyl-3-methylphenyl)-S-methylamino-2,3-dihydrofuran;
~ 2-~thien-2-yl)-3-oxo-4-(5-methoxy-3-ehlorophenyl)-S-; 20 methylamino-2,3-dihydrofuran;
2 (thien-2-yl)-3-oxo-4-(6-ethoxy-3-chlorophenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3,5-diethoxyphenyl)-5-methyl-- amino-2,3~dihydrofuran;
~5 2-tthien-2-yl)-3-oxo-4-(3-bromophenyl)-5 methylamino-2 t 3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-chloro-4-methylphenyl~-S-: methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-bromo-2-ethylphenyl)-S-methylamino-2,3-dihydrofuran;
. 2-(thien-2-yl)-3-oxo-4-(3,6-dimethylphenyl)-5-methyl-amino 2,3-dihydrofuran;
2-(thien-2-yl)-3~oxo 4-(3-iodo-4-msthylphenyl)-5-methylamino-2,3-dihydrofuran;
2 (thien-2-yl)-3-oxo-4 (3-chlorophenyl~-5 methyl-amino~2,3-dihydrofuran;
~-~thien-2-yl)~3~oxo-4-(3-butylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl~-3-oxo-4-(3-butoxyphenyl)-5-methyl-~ amino-2,3-dihydrofuran;
~Z55~
: 2-(thien-2-yl)-3-oxo-4-(3-isopropoxyphenylj-5-methyl-amino-2,3-dihydrofuran;
05 2-(thien-3-yl)-3-oxo-4-~3-bromophenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4 (3-iodophenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(2-methylphenyl)-5-methyl-amino-2,3-dihydrofuran;
2-(thien-3-yl~-3-oxo-4-(3-methoxyphenyl)-5-methyl-amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-fluorophenyl)-5-methyl-amino-2,3-dihydrofuran;
; lS 2-(thien-3-yl)-3-oxo-4-(3-propoxyphenyl)-5-methyl-amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-chlorophenyl)-5-methyl-amino-2,3-dihydrofuran;
2-(2,3-dihydrothien-2-yl)-3-oxo-4-(3-trifluoromethyl-phenyl)-5-methylamino-2,3-dihydrofuran;
2-(2,3-dihydrothien-2-yl)-3-oxo-4~(3,5-diethoxy-~ phenyl)-5-methylamino-2,3-dihydrofuran;
: 25 2-(tetrahydrothien-;3-yl)-3-oxo-4-(3-trifluoromethyl-phenyl)-5-methylamino-2,3-dihydrofuran;
2-(2H-thiopyran-2-yl)-3-oxo-4-(3-bromophenyl)-5-~ methylamino-2,3-dihydrofuran;
- 2-(2H-thiopyran-2-yl)-3-oxo-4-(2~chloro-3-trifluoro-methylphenyl)-5-methylamino-2,3-dihydrofuran;
~ 2-(fur-2-yl)-3-oxo-4-(5-chloro-3-trifluoromethyl-;:` phenyl)-5-methylamino-2,3-dihydrofuran, 2-(fur-2-yl)-3-oxo-4-(3-fluorophenyl)-5-methylamino-2,3-dihydrofuran;
2-(fur-2-yl3-3-oxo-4-(3-bromophenyl)-S-methylamino-2,3-dihydrofuran;
2 (fur-2-yl)-3-oxo-4-(3-chlorophenyl)-5-methylamino-2,3-dihydrofuran;
~-(fur-2-yl)-3-oxo-4-(3-m2thylphenyl)-5-methylamino-~ 2,3-dihydrofuran;
SS3~7 ~1 -22-2-(fur-~-yl)-3-oxo-4-(2-butoxy-3-trifluorome~hyl-phenyl)-5-methylamino-2,3-dihydrofur~n;
oS 2-(fur-2-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(fur-2-yl)-3-oxo-4-(3-iodophenyl)-5-methylamino-2,3-dihydrofuran;
2-(fur-2-yl)-3-oxo-4 13-propylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(2,3-dihydrofur-2-yl)-3-oxo-4-(3-trifluoromethyl-phenyl)-5-methylamino-2,3-dihydrofuran;
2-(2,3-dihydrofur-2-yl)-3-oxo-4-(2-bromo-3-trifluoro-methylphenyl)-5-methylamino-2,3-dihydrofuran;
lS 2-(tetrahydrofur-2-yl~-3-oxo-4-(3-trifluoromethyl-:` phenyl)-5-methylamino-2,3-dihydrofuran;
: 2-(tetrahydrofur-2-yl)-3-oxo-4-l4-methyl-3-trifluoro-; methylphenyl)-5-methylamino~2,3-dihydrofuran;
~: 2-(fur-3-yl)-3-oxo-4-(5-chloro-3-trifluoromethyl-~0 phenyl)-5-methylamino-2,3-dihydrofuran 2-(fur-3-yl)-3-oxo-4-l3-fluorophenyl)-5-methylamino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-bromophenyl)-5-methylamino-~; 2,3-dihydrofuran;
` 25 2-(fur-3-yl)-3-oxo-4~(3-chlorophenyl)-5-methylamino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-methylphenyl)-5-methylamino-:~ 2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(2-butoxy~3-trifluoromethyl-phenyl)-5 methylamino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-trifluoromethylphenyl~-5-methylamino-2,3-dihydrofuran;
2- ( f ur-3-yl)-3-oxo-4-(3-methoxyphenyl)-5-methylamino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-ethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-~2~3-dihydrofur-2-yl~-3-oxo-4-(3-trifluoromethyl-phenyl)~5-methylamino-2,3-dihydrofuran;
2-(2,3-dihydrofur-2-yl)-3-vxo~4-l2-hromo-3-trifluoro-methylphenyl)-5-methylamino-2,3-dlhydrofuran;
S3~7 01 -23~
2-~tetrahydrofur-3-yl)-3 oxo-4-(3-~rifluoromethyl~
phenyl)-5-methylamino-2,3-dihydrofuran;
05 2-~tetrahydrofur-3-yl)-3-oxo-4-(4-methyl-3-trifluoro-; methylphenyl)-5-methylamino-2,3-dihydrofuran, 2-~4H-pyran-2-yl)-3-oxo-4-(3-trifluoromethylphenyl~-5-methylamino-2,3-dihydrofuran;
2-~4H-pyran-2-yl)-3-oxo-4-(3-fluorophenyl)-5-methyl-amino-2,3-dihydrofuran;
2~(4H-pyran-2-yl)-3-oxo-4-(3-methylphenyl)-5-methyl-amino-2,3-dihydr3furan;
: 2-(4H-pyran-2-yl)~3-oxo-4-(2-methyl-3-trifluoro~
methylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(4H-pyran-2-yl)-3-oxo-4 (2-nitro-3-methylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(2H-3,4-dihydropyran-3-yl)-3-oxo-4-(3-trifluoro-methylphenyll-5 methylamino-2,3-dihydrofuran;
2-(2H-3,4-dihydropyran-3-yl)-3-oxo-4-(2-chloro-3 trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(2H-3,4-dihydropyran-3-yl~-3-oxo-4-(3-fluoro-:~ phenyl)-5-methylamino 2,3-dihydrofuran;
: 2-(2H-3,4-dihydropyran-4-yl)-3-oxo-4(3-methylphenyl)-5-methylamino-2,3-dihydro~uran;
2-(tetrahydropyran-2-yl)-3-oxo-4-(3-~rifluoromethyl-phenyl)-5-methylamino-213-dihydrofuran;
2-(tetrahydropyran-2-yl)-3-oxo-4-(3-chloro-5-methyl-phenyl)-5-methylamino-2,3-dihydrofuran;
2-(tetrahydropyran-3-yl)-3-oxo-4-(3-fluoroyhenyl)-5-methylamino-2,3-dihydrofuran; and 2-(tetrahydropyran-4-yl)-3-oxo-4-(3-ethylphenyl)-5-methylamino-2,3-dihydrofuran.
Example 5 2-(Thien-2-yl)-3-oxo-4-(3-trifluoro-methylp_~yl)-5-allylamino-2,3-dlhydrofuran This example illustrates a preparation which can be used to prepare the 5-allylamino substituted compounds of the invention.
~S3;~'7 ~1 -24-One gram of sodium hydroxide in 4.0 ml of water is added to a mixture of 1 mmol of 2-(thien 2-yll-3-oxo-4-05 (3 trifluoromethylphenyl)-5-amino-2,3-dihydrofuran in 80 ml of methylene chloride at room temperature followed by the addition of 1 mmol of allyl bromide and 0.27 9 of benzyltriethylammonium chloride The resulting mixture is stirred at room temperature for about 18 hours after which time it can be washed three times with water, dried over magnesium sulfate and concentrated in vacuo. The residue can ~e purified by chromatography over silica gel to yield the title compound.
Similarly, by applying this procedure to the products listed in Examples 3 and 4, the corresporlding 5-allylamino analogs thereof can bs prepared. Similarly, by approximately doubling the amount of allyl bromide and sodium hydroxide, the corresponding 5-diallylamino analogs thereof can be prepared.
In a like manner, by using ethyl bxomide in place of allyl bromide, the corresponding 5-ethyl and 5-diethyl analogs can be prepared.
Similarlyl by using the 5-methylamino analogs of Example 4 as starting materials, the corresponding 5-N-methyl-N-allylamino and 5-N-methyl-N-ethyl analogs can be prepared.
~ ~e~
Lithium salt of 2-thien 2-yl-3-oxo-4-(3-trifluoromethylphenyl)- `
5-methylamino-2,3-dihydrofuran (R~ R2-Li) This example illustrates a preparation which can be used to prepare the lithium salts of the invention.
In this example, 5.4 ml of 1.6M n-butyllithium in hexane i5 added dropwise to a stirred solution contain-ing 2.al 9 of 2-thien-2-yl-3-oxo-4-(3-trifluoromethyl-phenyl)-5 amino-2,3-dihydrofuran in 25 ml of tetrahydro-furan at -30C. The mixture is stirred for 20 minutes and can ~hen be concentrated by evaporation ln vacuo to yield the title compound.
, i! ;2~53~
01 ~-25-Similarly, by following the same procedure, the corresponding lithium salts of the compounds of 05 Examples 3-5 can bs prepared.
Example 7 The compounds listed in Table A hereinbelow were prepared using the appropriate starting materials and pro-cedures described in the Examples hereinabove.
`~ ~0 I
, ~: 35 :
~2S~3~L7 * #er ~ ~ ~ er .~ C ~, .,, o , o ~o _, ~ Ul U~
a~ ~ ~ ~r ~: , ,, ~ ~ , :, ~c ~
r~
o .....
g ~ ~r er eP ~r ~ .
., ~, Z _, ~ _, ~ _, ~
cn O ~
U~
¢ ~ ~
Z ~ ~ ~ ~ ~ ~ _, ~ ~ o . . . . .
o ~ ~ .
~ ~ Z ~C ~ O~n0~r~
c~
I ~ /Z~
/ ~ \ N r-lC O ~ ~ Lf') ~ CO
~ ~ Ln ~ t~ c~
.
f~
~ ~c s a~
s ~c s s ~
J~
3 3 ~ ~ O
~ O
ol Z I ~ ~
Ln O U- o Ul o ~7 ~ _I ~ ~
~:
3L~S5~
~l -27-~.
In this example, the compounds of Table A were 05 respecti~ely tested using the procedures described herein-below for pre-emergent and post-emergent activity against a variety of grasses and broad-leaf plants including one grain crop and one broad-leaf crop. The compounds tested are identified by compound number in Table A hereinabove.
Pre-Emergent Herbicide Test Pre-emergence herbicidal activity was determined in the following manner.
Test solutions of the respective compounds were prepared as follows:
35515 mg of test compound was dissolved in 15 m~
of acetone. 2 ml of acetone containing llO mg of a non-ionic surfactant was added to the solution. 12 ml of this stock solution was then added to 47.7 ml of water which contained the same nonionic surfactant at a concentration ~; 20 of 625 mg/l.
Seeds of the test veyetation were planted in a pot of soil and the test solution was sprayed uniformly onto the soil surface either at a dcse of 27.5 micro-grams/cm2. The pot was watered and placed in a green-house. The pot was watered intermittently and observed for seedling emergence, health of emerging seedlings, etc., for a 3-week periodO At the end of this period, the herbicidal effectiveness of the compound was rated based on the physiological observations~ A 0-to-lO0 scale was used, 0 representing no phytotoxicity, lO0 representing complete kill. The results of these tests are summarized in Table l.
Post-Emergent Herbicidal Te~t The test compound was formulated in the same manner as described above for the pre-emergent ~est.
This formulation was uniformly sprayed on 2 similar pots containing plants ~ to 3 inches tall (except wild oats, soybean and watergrass which were 3 to 4 inches tall) ~approximately 15 to 25 plants per pot) at a dose of 27.5 microgram/cm~. After the plants had dried, they were .
~2S~i3~7 placed in a greenhouse and then watered intermittsntly at their bases as needed. The plants were observed periodic-o~ ally for phytotoxic effects and physiological and morpho-logical responses to the treatment, After 3 weeks, the herbicidal effectiveness of the compound was rated based on these observations. A 0-to-100 scale was used, 0 representing no phytotoxicity, 100 representing complete kill. The results of these tests are summarized in Table 2.
Pre-Emergence Herbicidal Activity Application Rate: 27.5 micrograms/cm2, unless otherwise noted Broad~Leaf Plants Grasses Com-- % Ph~toxicity ~ 3~959~19~ ~
pound Lambs- Pig Soy Crab Water Wild : No. _ 5~ Mustarù weed bean 9~ grass Oats Rice 1 , 100 100 100100 100 100 99 g7 3 100 10~ 10090 100 100 100 100 4 100 100 100100 1~0 100 100 100 TA~LE 1 Application Rate: 27.5 micrograms/cm29 : 30 unless otherwise noted Broad-Leaf Plants Grasses Com- % Phytotoxicity_ % Phytotoxicity ~ pound Lambs- Pig Soy Crab Water Wild : No. ~uart r Mustard weed bean ~rass 9~ Oats Rice 1 ~5 9g ~8 38 45 60 65 30 ~:; 3 70 90 65 70 80 60 75 25 ~ 4 Not Test0d : 5 85 95 70 90 70 90 93 70 ::~ 4~
~;~5S3~7 As can be seen from the above Table 1, the tes~
compounds of the invention exhibited a broad spectrum of oS excellent pre-emergence phytotoxic activity. Moreover, as shown by Table 2 the compounds also exhibit a broad spec-trum of post-emergence phytotoxic activity and especially so Compound No. 2.
: Obviously, many modifications and variations of the invention described hereinabove and below can be made without departing from the essence and scope thereof.
:: 2 ~' :
':
~0 :
Suitable strong bases which can be used include, for example, sodium hydroxide, potassium hydroxide, sodium ethoxide, sodium carbonate, potassium carbona~e, and the like.
Suitable phase transfer agents are agents whi~h transfer hydrophilic ions into a lipophilic oryanic medium and include, for example, benzyl triethylammonium chloride, ~etra-n-butylammonium chloride, methyltrioctylammoni.um chloride, and ;~ the like.
The compatible salts of Formula (I) can be prepared by conventional procedures ky treating the compound of Formula ~I) wherein R1 andtor R2 is hydrogen with a suita~le strong base such as, for example, n-butyllithium, sodium hydride, potassium hydride, and the like, having the desired cation, by : 30 conventiollal procedures to replace an amine hydrogen wi~h the ~ ` ~ fl 7 . ~, .
~55~:~7 61g36-1665 desired carbon. The -three-position enolate salts can be prepared via further treatment of the amine salt with base.
Additional variati.ons in the salt cation can also be effected via ion exchange with an ion exchange resin having the desired cation.
General Process Conditions In the above-described processes, it is generally preferable to separate the respective products before 7a ,, ,~
~ . ~. /
. . , " '' ;
3:a7 Ol -8 proceeding with the next step in the reaction sequence, cxcept where described as an in situ step or unless other-05 wise expressly stated. These products can be recoveredfrom their respective reaction produet mixtures by any suitable separation and purification procedure, such as, for example, recrystallization and chromatography. Suit-able ~eparation and purification procedures are, for exam-~le, illu5tratsd in the Examples set forth hereinbelow.
Generally, the reactions described above areconducted as liquid phase reaction and hence pressure is generally not significant except as it affects temperature (boiling point) where reactions are conducted at reflux~
lS Therefore, these rcactions are generally conducted at pressures of about from 300 to 3,000 mm of mercury and ` conveniently are conducted at about atmospheric or ambient pressure~
It should also be appreciated that where typical or preferred process conditions (e.g., reaction tempera-tures, times, mole ratios of reactant~, solvents, etc.) have been given, that other process conditions could also be used. Optimum reaction conditions (e.g., temperature, reaction time, mol ratios, solvents, etc~ may vary with the particular reagents or organic solvents used but can be determined by routine optimization procedures.
Where optical isomer mixtures are obtained, the respective optical isomers can be obtained by conventional resolution procedures~ Geometric isomers can be scparated by conventional separation procedures which depend upon differences in physical properties between the geometric isomers.
~efinitions As used herein the following terms have the following meanings unless expressly stated ~o the contrary:
The term "lower alkyl" refers to both straight and branched-chain alkyl groups having a total of from 1 through ~ r pre~erably 1 through 4, carbon atoms and includes primary, secondary and tertiary alkyl groups.
;5~
61936-lG65 Typical lower alkyls include, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, t-butyl.
The term "lower alkenyl" refers to alkenyl groups having 2 through 6, preferably 2 through 4, carbon atoms and includes, for example, vinyl, 1-propenyl, 2-propenyl, 1-methylvinyl, 1-butenyl, 2-methylprop-1-enyl and the like.
The term "halo" refers to the group of fluoro, chloro, bromo and iodo.
The term "aryl" refers to aryl groups having 6 through 10 carbon atoms and includes, for example, phenyl, naphthyl, indenyl, and the like.
The term "substituted aryl" refers to aryl groups having 1 through 3 substituents independently selected from the group of lower alkyl, lower alkoxy, halo, nitro, or haloalkyl having 1 throuyh 3 carbon atoms and 1 through 3 halo atoms.
Typical substituted aryl groups include, for example, 2-fluoro-phenyl, 2-chlorophenyl, 2,6-dimethylphenyl, 4-fluorophenyl, 2-methylphenyl, 2-chloro, 4-chloromethylphenyl, 2-nitro,5-methylphenyl, 2,4-dichlorophenyl, 3-trifluoromethylphenyl, 2-methoxyphenyl, and the like.
The term "arylalkylene" or "arylalkyl" refers to the group ArRS- wherein Ar is aryl and R5 is alkylene having 1 through 3 carbon atoms and includes both straight-chained and branched-chained alkylenes, for example, methylene, ethyl, 1-methylethyl, and propyl.
The term "~substituted aryl)alkylene" or "ring-substituted arylalkylene" refers to the group Ar'R5- wherein Ar' is substituted aryl and R5 is alkylene as defined with respect to arylalkylene.
.
The term "compatible salts" refers to salts which do not significantly alter the herbicidal properties of the parent compound. Suitable salts include cation salts su~h as, for example, the cation replacement salts of lithium, sodium, potassium, alkali earth metals, ammonia, quaternary ammonium salts, and the like.
9a S3~7 The term ~room temperature" or ~ambient temper-ature" refers to about 20-25C.
~5 ~
The compounds of Formula (I) exhibit both pre-emergence and post-emergence herbicidal activity and exhibit especially good pre-emergence herbicidal activity.
Generally, for post-emergent applications, the herbicidal compounds are applied directly to the foliage or other plant parts. For pre-emergence applications, the herbicidal compounds are applied to the growth medium, or prospective growth medium, for the plant. The optimum amount of the herbicidal compound or composition will vary with the particular plant species, and the extent of plant growth, if any, and the particular part of the plant which is contacted and the extent of contact. The optimum dosage can also vary with the general location, or i environment (e.g., shelter~d areas such as greenhouses ~; 20 compared to exposed areas such as fields), and type and ~ degree of control desired. Generally, for both pre- and ;~ post-~mergen~ con~rol, the present compounds are applied at rates of about from 0~02 to 60 kg/ha, preferably about from 0.02 to lO kg/ha.
;~ 25 Also, although in theory the compounds can be applied undiluted, in actual practice they are generally applied as a composition or formulation comprising an effective amount of the compound(s) and an acceptable car-rier. An acceptable or compatible carrier (agriculturally acceptable carrier) is one which does not significantly adversely affect the desired biological effect achieved by the active compounds, save to dilute it. Typically, the composition contains about from 0~05 to 95% by weight of the compound of Formula (I) or mixtures thereof . Concen-trates can also be made having high concentrations designed for dilution prior to application, The carrier can be a solid, liquid, or aerosol. The actual com~osi-tions can take the form of granules, powders, dusts, solu-tions, emulsions, slurries, aerosols, and the like.
5~7 Suitable solid carriers which can be used include, for example, natural clays ~such a kaolin, 05 ~ttapulgite, montmorillonite, etc.), talcs, pyrophyllite, diatomaceous silica, synthetic fine silica, calcium alumi-nosilicate, tricalcium phosphate, and the like. Also, organic materials, such as, for example, walnut shell flour, cotton-seed hulls, wheat flour, wood flour, wood bark flour, and the like can also be used as carriers.
Suitable liquid diluents which can be used include, for example, water, organic solvents (e.g., hydrocarbons such as benzene, toluene, dimethylsulfoxide, kerosene, diesel fuel, fuel oil, petroleum naphtha, e~c.), and the like.
Suitable aerosol carriers which can be used include con-ventional aerosol carriers such as halogenated alkanes, etc.
The composition can also contain various promo-ters and surface-active agents which enhance the rate of transport of the active compound into the plant tissue such as, for example, organic solvents, wetting agents and oils, and in the case of compositions designed for pre-emergence application agents which reduce the leachability of the compound or otherwise enhance soil stability.
The composition can also contain various com-patible adjuvants, stabilizers, conditioners, insecti-cides, fungicides, and if desired, other herbicidally ~; active compounds.
At reduced dosages the compounds of the present invention also exhibit plant growth regulating activity and can be used to alter the normal growth pattern of green plants.
The compounds of Formula (I) can be applied as plant growth regula~ors in pure form, but more pragmatic-ally/ as in the case of herbicidal application, are applied in combination with a carrier. The same types of carriers as set forth hereinabove with respect to the herbicidal compositions can also be used. Depending on the desired application, the plant growth re~ulating com-;~ 40 position can also contain, or be applied in combination ~S~i3~
l2-with other compatible ingredien~s such as desiccants, defoliants, surace-active a~ents, adjuvants, fungicides, 05 and insecticides. Typically, the plant gr~wth regulating composition will contain a total of about from 0.005 to 90 wt. % of the compound(s) of Formula (I~ depending on whether the composition is intended to be applied directly or diluted first.
A further understanding of the invention can be had in the following non-limiting Preparation and Examples. Wherein, unless expressly stated to the con-trary, all temperatures and temperature ranges refer to the Centigrade system and the term Nambient" or Uroom temperature" refers to about 20-25C. The term "percent"
or ~" refers to weight percent and the tenm "mole" or moles~ refers to ~ram moles. ~he term "equivalent"
refers to a quantity of reayent equal in moles, to the ~ moles of the precedin~ or succeeding reactant rscited in `~ 20 that example in terms of finite moles or finite weight or volume. Where given, proton-magnetic resonance spectrum ;~ (p.m.r. or n.m.r.) were determined at 60 mHz, signals are assigned as singlets (s), broad singlets (bs), doublets (d), double doublets (dd), triplets ~t), double triplets (dt), quartets (q~, and multiplets (m); and cps refers to cycles per second. Also where necessary, examples are repeated to provide additional starting material for sub-sequent examples.
EXA~PLES
3C Example l . ~
In this example 25.0 y of 2-formylthiophene was added to a stirred solution containing lO.93 9 of sodium cyanide in 37 ml of water at room temperature. 63 ml of 3S aqueous satura~ed sodium acid sulfite was then slowly added to the stirred mixture. During the addition of the ; sodium acid ~ulfite solution, small amounts (about 20 9) of ice were periodically added The mixture was then s~irred for another l~ minutes and extracted with ethyl e~her. The ethyl ether extracts were combined, dried over , 53~'7 magnesium sulfate and evaporated under vacuum affording 18.4 g of the title compound.
~xample 2 Methyl T ~
(a) In this example 6.8 9 of methanol was added to a stirred solution of 26.9 9 of thienyl-2-yl-hydroxy-acetonitrile in 100 ml ethyl ether at about 10C~ Hydro-gen chloride was then bubbled through this mixture until the formation of a salt precipitate was observed. The mixture was then stirred for about 15 minutes at about 10C and then filtered. The filter cake was washed with ethyl ether and then evaporated affording 18.2 g of the chloride salt of 2-(2-imino-2-methoxy-1-hydroxyethyl)thio-phene.
(b) The above salt was then dissolved in water and stirred at room tempera~ure for about 30 minutes and then extracted three ~imes with ethyl ether.
The ethyl ether extracts were combined, dried over magnesium sulfate and concentrated by evaporation under vacuum, affording 8.3 9 of the title compound.
The filtrate from step (a) was allowed to stand overnight (about 16-18 hours) at room temperature and was then filtered. The filter cake was treated as before affording an additional 11.7 g of chloride salt. This salt was then hydrolyzed with water as described above affording an additional 4~4 g of the title compound.
Similarly, by applying the procedures of Examples 1 and 2 using the a~propriate heterocyclic-hydroxyacetonitrile star~ing material~ in Example 1, the following compounds can be prepared.
Methyl thien-3-yl-hydroxyacetate;
Methyl(2,3 dihydrothien 2-yl~-hydroxyacetat~
Methyl tetrahydrothien-3-yl-hydroxyacetate;
Methyl(2H-thiopyran-2-yl)-hydroxyacetate Methyl fur-2-yl-hydroxyacetate;
Methyl fur-3-yl-hydroxyacetate;
Methyl(2,3-dihydrofur-2-yl)-hydroxyacetate;
Methyl tetrahydrofur-3-yl hydroxyacetate;
~X~
Methyl~4H-pyran-2-yl) hydroxyacetate;
Methyl(2H 3,4-dihydropyran-3 yl)-hydroxyacetate; and 05 Methyl(tetrahydropyran-2-yl)-hydroxyacetateO
Example 3 2-Thien-2-yl-3-oxo-4-(3-trifluoromethylphenyl)-5-amino-2 3-dihvdrofuran A dry, 250-ml, three-neck, round-bottom flask equipped with a mechanical stirrer, addition funnel and a reflux condenser bearing a nitrogen inlet tube was charged ~ with 4.2 ~ of sodium and lO0 ml of absolute ethanol. To i~ the resulting sodium ethoxide solution was added dropwise ~ a mixture of 21 o l g Of methyl thien-2-yl hydroxyacetate ;~ 15 and 22.7 g of m-trifluoromethylphenyl-acetonitrile in 20 ml of ethanol. The resulting mixture was heated at reflux for 4-5 hours after which time it was added to 300-400 ml of water and extracted with petroleum ether.
The aqueous phase was acidified with aqueous lO weiyht percent hydrochloric acid and extracted two times with diethyl ether. The ether extracts were washed twice wi~h ~; saturated aqueous sodium bicarbonate, dried over magnesium sulfate and concentrated in vacuo to yield a thick dark oil~ This oil was triturated with 20-30~ ether/petroleum ether which afforded 4.9 9 of the ~itle compound as a tan powder.
Similarly, by applying the above-described pro-cedure using the appropriate (substituted phenyl) aceto-nitrile starting materials the following eompounds can also be prepared:
2-(thien-2-yl)-3-oxo-4-~5-ehloro-3-trifluoromethyl-phenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(4-chloro-3-~rifluoromethyl-phenyl)-5-amino-2,3 dihydrofuran;
2-(thien-2-yl)~3-oxo-4-(2-bromo-3-trifluoromethyl-~` phenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-[6-fluoro--3 trifluoromethyl-phenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(4 methyl-3-trifluoromethyl-phenyl)-5-amino 2,3 dihydrofuran;
.~
~53~7 2-(thien-2 yl)-3-oxo-4-(5-methoxy-3-trifluoromethyl-phenyl)~5-amino-2,3 dihydrofuran;
05 2-(thien-2-yl)-3-oxo-4-(6-isopropyl-3-trifluoro-methylphenyl)-5-amino-2,3-dihydrofuran 2-(thien-2-yl)-3-oxo-4-(3,5-di-trifluoromethylphenyl~-5-amino-2,3-dihydrofuran;
2-(thien-2-yl) 3-oxo-4-(3-propylphenyl)-5-amino-2,3-dihydrofuran;
2-~thien-2-yl)-3-oxo-4-(3-methylphenyl)-S-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-fluorophenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-methoxy~henyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-iodophenyl)-5-amino-2,3-dihydrofuran; and 2-(thien-2-yl)-3-oxo-4-(2-chloro-3-methylphenyl)-5-amino-2,3-dihydrofuran;
2-~thien-2-yl)-3-oxo-4-(4-ethyl-3-methylphenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-~5-methoxy-3-chlorophenyl)-5-amino-2,3-~ihydrofuran;
2-(thien-2-yl)-3-oxo-4-(6-ethoxy-3-chlorophenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3~oxo~4-(3,5-diethoxyphenyl)-5-amino-2,3-dihydrofuran;
~: 2-(thien-2-yl)-3-oxo-4-(3-brsmophenyl)-5-amino-2,3-; 30 dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-chloro-4-methylphenyl)-S-~ amino-2,3-dihydrofuran;
: 2-(thien-2-yl)-3-oxo-4-(3-bromo-2-ethylphenyl)-S-amino-2,3-dihydrofuran;
2-~thien-2-yl)-3-oxo-4-(3,6-dimethylphenyl)-5-amino-2,3--dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-iodo-4-methylphenyl)-5-amino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-chlorophenyl)-5-amino-2,3-dihydrofuran;
.,, ~l~2S53~7 2-(thien-2-yl)-3-oxo-4-~3-butylphenyl)-5-amino-2,3-dihydrofuran;
05 2-(thien-2-yl)-3-oxo-4-(3-butoxyphenyl)-5-amino-2,3-dihydrofuran; and 2-~thien-2-yl)-3-oxo-4-(3-isvpropoxyphenyl)-5-amino-2,3-dihydrofuran.
Similarly by applying the above procedure using the appropriate (substituted phenyl)acetonitrile and the appropriate methyl heterocycle-hydroxyacetate compound of the list given in Example 2 the corresponding 2~hetero-cycle analogs of the a~ove compounds can also be prepared for example:
;~ 2-~thien-3-yl)-3-oxo-4-(3-bromophenyl)-5-amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-t3-iodophenyl)-5 amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-propylphenyl)-5-amino-2,3-2U dihydrofuran;
2-(thien~3-yl~-3-oxo-4-(3-methoxyphenyl) 5-amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-fluorophenyl)-5-amino-2,3-dihydrofuran; and ~5 2-(thien-3-yl)-3-oxo-4-(3-propoxyphenyl)-5-amino-2,3-dihydrofuran.
2-(thien-3-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-chlorophenyl)-5-amino-2,3-~ 30 dihydrofuran;
- 2-(2,3-dihydrothien-2-yl)-3-oxo-4-(3-trifluoromethyl-: phenyl)-5-amino-2,3-dihydrofuran;
2-(2,3-dihydrothien-2-yl)-3-oxo-4-(3,5-diethoxy-~ phenyl)-5-amino-2,3-dihydrofuran;
~ 2-(tetrahydrothien-3-yl)-3-oxo-4-~3-trifluoromethyl-phenyl)-5-amino-2,3-dihydrofuran;
2-(?H-thiopyran-2-yl)-3-oxo-4-(3-bromophenyl)-5-amino-2,3-dihydrofuran;
2-(2H-thiopyran-2-yl)-3-oxo-4-(2-chloro-3-trifluoro-methylphenyl)-5-amino-2,3-dihydrofuran, ~S~3~'7 2-~fur-~-yl)-3 oxo-4-t3-trifluoromethyl-5-chloro-phenyl)-5-amino-2,3-dihydrofuran;
05 2-(fur-2-yl)-3-oxo-4-(3-fluorophenyl)-5-amino-2,3-dihydrofuran;
2-(fur-2-yl)-3~oxo-4-(3-bromophenyl)-5-amino-2,3-dihydrofuran;
2-(fur-2-yl)-3-oxo-4-(3-chlorophenyl)-S-amino-2,3-dihydrofuran;
2-(fur-2 yl)-3-oxo-4-(3-methylphenyl~-5-amino-2/3~
dihydrofuran;
2-(ur-2-yl)-3-oxo 4-(2-butoxy-3-trifluoromethyl-phenyl)-5-amino-2,3-dihydrofuran;
2-(fur-2-yl)~3-oxo-4-(3-trifluoromethylphenyl~-5-amino-2,3-dihydrofuran;
2-(fur-2-yl)-3-oxo-4-(3-iodophenyl)-5-amino-2,3-dihydrofuran;
2-(fur-2-yl~-3-oxo-4-(3-pro~ylphenyl)-S-amino-2,3-dihydrofuran;
2-(2,3-dihydrofur-2-yl)-3-oxo-4-(3-trifluoromethyl-~ phenyl)-5-amino-2,3-dihydrofuran;
`~ 2-(2,3-dihydrofur-2-yl)-3-oxo-4-(2-bromo-3-trifluoro-methylphenyl)-5-amino-2,3-dihydrofuran;
2-(tetrahydrofur-2-yl)-3-oxo-4-(3-trifluoromethyl-. phenyl)-5-amino-2,3-dihydrofuran;
2-(tetrahydrofur-2-yl)-3-oxo-4-(4-me~hyl-3-tri~luoro-methylphenyl)-5-amino-2,3-dihydrofuran;
~ 2-(fur-3-yl)-3-oxo-4-(5-chloro-3-trifluoromethyl-:: 30 phenyl~5-amino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-fluorophenyl)-S-amino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-bromophenyl)-5-amino-2/3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-chlorophenyl)-S-amino-2,3-dihydrofuran;
2~fur-3-yl)-3-oxo-4-(3-methylphenyl)-5-amino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(2-butoxy-3-~rifluoromethyl-p~enyl)-5-amino-2,3-dihydrofuran;
., ~2~53~
~1 -18-2-~ur-3-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-amino-2,3-dihydrofuran;
05 2- ( f ur-3-yl)-3-oxo-4-(3-methoxyphenyl)-5-amino-2,3-dihydrofuran;
2-lfur-3-yl)-3-oxo-4-(3-ethylphenyl)-5-amino-2,3-dihydrofuran;
2-~2,3-dihydrofur-2-yll-3-oxo-4-(3-trifluoromethyl-phenyl)-5-amino-2r3-dihydrofuran;
2-~2,3-dihydrofur-2-yl)-3-oxo-4-(2-bromo-3-trifluoro-methylphenyl)-5-amino-2,3-dihydrofuran;
2-(tetrahydrofur-3-yl)-3-oxo-4-(3-trifluoromethyl-phenyl)-5-amino-2,3-dihydrofuran;
~ 15 2-(tetrahydrofur-3-yl)-3-oxo-4-(4-methyl-3-trifluoro-: methylphenyl)-5-amino-2,3-dihydrofuran;
2 (4H-pyran-2-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-amino-2~3-dihydrofuran;
2-~4H-pyran-2-yl)-3-oxo-4-~3-fluorophenyl3-5-amino-2,3-dihydrofuran;
2-~4H-pyran-2-yl)-3-oxo-4-(3-methylphenyl)-5-amino-2,3-dihydrofuran;
2-(4H-pyran-2-yl)-3-oxo-4-(2-methyl-3-trifluoro-methylphenyl)-5-amino-2,3-dihydrofuran;
2-(4H-pyran-2-yl)~3-oxo-4-(2-nitro-3-methylphenyl)-5-amino-2 r3-dihydrofuran;
2-~2H-3,4-dihydropyran-3-yl)-3-oxo-4-(3-trifluoro-methylphenyl)-5-amino-2,3-dihydrofuran;
2-~2H-3,4-dihydropyran-3-yl~-3-oxo-4-~2-chloro-3-~: 30 trifluoromethylphenyl)-5-amino-2,3-dihydrofuran;
2-~-2H-3,4-dihydropyran-4-yl)-3-oxo-4-(3-fluoro-phenyl) 5-amino-2,3-dihydrofuran;
2-~2H-3,4-dihydropyran-3-yl)-3-oxo-4-(2-chloro-3-~: methylphenyl~-5-amino-2,3-dihydrofuran;
~ 2-(tetrahydropyran-2-yl)-3-oxo-4-(3-trifluoromethyl-~ phenyl)-5-amino-2~3-dihydrofuran;
:~ 2 tetrahydropyran-2-yl-3-oxo-4-(3-chloro-5-methyl-: phenyl)-5-amino-2,3-dihydrofuran;
2-( tetrahydropyran-2~yl ) -3 oxo-4- ( 3-fluorophenyl)-5-~ amino-2,3-dihydrofuran; and .~
~1936-1665 2-ltetrahydropyran-2-yl)-3-oxo-4-l3-ethylphenyl)-5-amino-~,3-dihydrofuran.
Example 4 2-Thien-2-yl-3-oxo-4-(3-trifluoromethylphenyl)-_ _ 5-methylamino-2~3-dihydrofuran In thi~ example about 0.36 g of ~olid sodium hydroxide was dissolved in a small amount oE water and then added to 100 ml of methylene ~hlorid~ containin~ 1.4 g of 2-thien-2-yl-3-oxo-4-(3-trifluoromethylphenyl)-5-amino-2,3-dihydrofuran. 0.20 g of benzyltriethylammonium ~hloride was added and then a mixture containing O.B4 ml of dimethyl sulfate in a~out 5.0 ml of methylene chloride was slowly added at room temperature. The mixture was stirred at room temperature for about one hour and then washed twice with water, twice with N. aqueous hydrochloric acid, twice with sodium bicarbonate, dried over magnesium sulfate and then concentra~ed by evaporation under vacuum. The residue was then triturated in a mixture of ethyl ekher and petroleum ether affording 1.4 g of the title compound.
Similarly, by following the ~ame procedure usiny the products listed ln Example 3 as starting materials, the corresponding 5-methylamino homoloys thereof can be prepared, for example:
2-(thien-2-yl)-3-oxo-4-(5-chloro-3-trifluoromethyl-phenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(4-chloro-3-tri~luoromethyl-phenyl)-5 methylamino-2,3-dihydrofuran;
2-l~hien-2-yl)-~-oxo-4-(2-bromo-3-triiluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-~6-fluoro-3-trifluoromethyl-phenyl)-5-methylamino-2,3-dihydrofuran;
~ 19 2-(~hien-2~yl)-3-oxo-4-(4-methyl~3-trifluoromethylphenyl)-5-methylamino-2,3~dihydrofuran;
2-(thien-2-yl)-3-oxo-4(5-methoxy-3-trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(6-isopropyl-3-trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
r l9a ~5~7 2-~thien-2-yl)-3-oxo-4-(3,5-di-trifluoromethyl-phenyl)-S-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-propylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-methylphenyl)~5-methylamino-2,3 dihydrofuran;
2-(thien-2-yl)~3-oxo-4-(3-fluorophenyl)-S-methyl-amino-2,3-dihydrofuran;
2 (thien-2-yl)-3-oxo-4-(3-methoxyphenyl)-5-methylam.ino-2~3-dihydrofuran;
2-(thien 2-yl)-3-oxo-4-(3-iodophenyl)-5-methylamino-2,3-dihydrofuran; and ~ lS 2-(thien-2-yl)-3-oxo-4-(2-chloro-3-methylphenyl~-5-: methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(4-ethyl-3-methylphenyl)-S-methylamino-2,3-dihydrofuran;
~ 2-~thien-2-yl)-3-oxo-4-(5-methoxy-3-ehlorophenyl)-S-; 20 methylamino-2,3-dihydrofuran;
2 (thien-2-yl)-3-oxo-4-(6-ethoxy-3-chlorophenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3,5-diethoxyphenyl)-5-methyl-- amino-2,3~dihydrofuran;
~5 2-tthien-2-yl)-3-oxo-4-(3-bromophenyl)-5 methylamino-2 t 3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-chloro-4-methylphenyl~-S-: methylamino-2,3-dihydrofuran;
2-(thien-2-yl)-3-oxo-4-(3-bromo-2-ethylphenyl)-S-methylamino-2,3-dihydrofuran;
. 2-(thien-2-yl)-3-oxo-4-(3,6-dimethylphenyl)-5-methyl-amino 2,3-dihydrofuran;
2-(thien-2-yl)-3~oxo 4-(3-iodo-4-msthylphenyl)-5-methylamino-2,3-dihydrofuran;
2 (thien-2-yl)-3-oxo-4 (3-chlorophenyl~-5 methyl-amino~2,3-dihydrofuran;
~-~thien-2-yl)~3~oxo-4-(3-butylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-2-yl~-3-oxo-4-(3-butoxyphenyl)-5-methyl-~ amino-2,3-dihydrofuran;
~Z55~
: 2-(thien-2-yl)-3-oxo-4-(3-isopropoxyphenylj-5-methyl-amino-2,3-dihydrofuran;
05 2-(thien-3-yl)-3-oxo-4-~3-bromophenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4 (3-iodophenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(2-methylphenyl)-5-methyl-amino-2,3-dihydrofuran;
2-(thien-3-yl~-3-oxo-4-(3-methoxyphenyl)-5-methyl-amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-fluorophenyl)-5-methyl-amino-2,3-dihydrofuran;
; lS 2-(thien-3-yl)-3-oxo-4-(3-propoxyphenyl)-5-methyl-amino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(thien-3-yl)-3-oxo-4-(3-chlorophenyl)-5-methyl-amino-2,3-dihydrofuran;
2-(2,3-dihydrothien-2-yl)-3-oxo-4-(3-trifluoromethyl-phenyl)-5-methylamino-2,3-dihydrofuran;
2-(2,3-dihydrothien-2-yl)-3-oxo-4~(3,5-diethoxy-~ phenyl)-5-methylamino-2,3-dihydrofuran;
: 25 2-(tetrahydrothien-;3-yl)-3-oxo-4-(3-trifluoromethyl-phenyl)-5-methylamino-2,3-dihydrofuran;
2-(2H-thiopyran-2-yl)-3-oxo-4-(3-bromophenyl)-5-~ methylamino-2,3-dihydrofuran;
- 2-(2H-thiopyran-2-yl)-3-oxo-4-(2~chloro-3-trifluoro-methylphenyl)-5-methylamino-2,3-dihydrofuran;
~ 2-(fur-2-yl)-3-oxo-4-(5-chloro-3-trifluoromethyl-;:` phenyl)-5-methylamino-2,3-dihydrofuran, 2-(fur-2-yl)-3-oxo-4-(3-fluorophenyl)-5-methylamino-2,3-dihydrofuran;
2-(fur-2-yl3-3-oxo-4-(3-bromophenyl)-S-methylamino-2,3-dihydrofuran;
2 (fur-2-yl)-3-oxo-4-(3-chlorophenyl)-5-methylamino-2,3-dihydrofuran;
~-(fur-2-yl)-3-oxo-4-(3-m2thylphenyl)-5-methylamino-~ 2,3-dihydrofuran;
SS3~7 ~1 -22-2-(fur-~-yl)-3-oxo-4-(2-butoxy-3-trifluorome~hyl-phenyl)-5-methylamino-2,3-dihydrofur~n;
oS 2-(fur-2-yl)-3-oxo-4-(3-trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(fur-2-yl)-3-oxo-4-(3-iodophenyl)-5-methylamino-2,3-dihydrofuran;
2-(fur-2-yl)-3-oxo-4 13-propylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(2,3-dihydrofur-2-yl)-3-oxo-4-(3-trifluoromethyl-phenyl)-5-methylamino-2,3-dihydrofuran;
2-(2,3-dihydrofur-2-yl)-3-oxo-4-(2-bromo-3-trifluoro-methylphenyl)-5-methylamino-2,3-dihydrofuran;
lS 2-(tetrahydrofur-2-yl~-3-oxo-4-(3-trifluoromethyl-:` phenyl)-5-methylamino-2,3-dihydrofuran;
: 2-(tetrahydrofur-2-yl)-3-oxo-4-l4-methyl-3-trifluoro-; methylphenyl)-5-methylamino~2,3-dihydrofuran;
~: 2-(fur-3-yl)-3-oxo-4-(5-chloro-3-trifluoromethyl-~0 phenyl)-5-methylamino-2,3-dihydrofuran 2-(fur-3-yl)-3-oxo-4-l3-fluorophenyl)-5-methylamino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-bromophenyl)-5-methylamino-~; 2,3-dihydrofuran;
` 25 2-(fur-3-yl)-3-oxo-4~(3-chlorophenyl)-5-methylamino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-methylphenyl)-5-methylamino-:~ 2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(2-butoxy~3-trifluoromethyl-phenyl)-5 methylamino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-trifluoromethylphenyl~-5-methylamino-2,3-dihydrofuran;
2- ( f ur-3-yl)-3-oxo-4-(3-methoxyphenyl)-5-methylamino-2,3-dihydrofuran;
2-(fur-3-yl)-3-oxo-4-(3-ethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-~2~3-dihydrofur-2-yl~-3-oxo-4-(3-trifluoromethyl-phenyl)~5-methylamino-2,3-dihydrofuran;
2-(2,3-dihydrofur-2-yl)-3-vxo~4-l2-hromo-3-trifluoro-methylphenyl)-5-methylamino-2,3-dlhydrofuran;
S3~7 01 -23~
2-~tetrahydrofur-3-yl)-3 oxo-4-(3-~rifluoromethyl~
phenyl)-5-methylamino-2,3-dihydrofuran;
05 2-~tetrahydrofur-3-yl)-3-oxo-4-(4-methyl-3-trifluoro-; methylphenyl)-5-methylamino-2,3-dihydrofuran, 2-~4H-pyran-2-yl)-3-oxo-4-(3-trifluoromethylphenyl~-5-methylamino-2,3-dihydrofuran;
2-~4H-pyran-2-yl)-3-oxo-4-(3-fluorophenyl)-5-methyl-amino-2,3-dihydrofuran;
2~(4H-pyran-2-yl)-3-oxo-4-(3-methylphenyl)-5-methyl-amino-2,3-dihydr3furan;
: 2-(4H-pyran-2-yl)~3-oxo-4-(2-methyl-3-trifluoro~
methylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(4H-pyran-2-yl)-3-oxo-4 (2-nitro-3-methylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(2H-3,4-dihydropyran-3-yl)-3-oxo-4-(3-trifluoro-methylphenyll-5 methylamino-2,3-dihydrofuran;
2-(2H-3,4-dihydropyran-3-yl)-3-oxo-4-(2-chloro-3 trifluoromethylphenyl)-5-methylamino-2,3-dihydrofuran;
2-(2H-3,4-dihydropyran-3-yl~-3-oxo-4-(3-fluoro-:~ phenyl)-5-methylamino 2,3-dihydrofuran;
: 2-(2H-3,4-dihydropyran-4-yl)-3-oxo-4(3-methylphenyl)-5-methylamino-2,3-dihydro~uran;
2-(tetrahydropyran-2-yl)-3-oxo-4-(3-~rifluoromethyl-phenyl)-5-methylamino-213-dihydrofuran;
2-(tetrahydropyran-2-yl)-3-oxo-4-(3-chloro-5-methyl-phenyl)-5-methylamino-2,3-dihydrofuran;
2-(tetrahydropyran-3-yl)-3-oxo-4-(3-fluoroyhenyl)-5-methylamino-2,3-dihydrofuran; and 2-(tetrahydropyran-4-yl)-3-oxo-4-(3-ethylphenyl)-5-methylamino-2,3-dihydrofuran.
Example 5 2-(Thien-2-yl)-3-oxo-4-(3-trifluoro-methylp_~yl)-5-allylamino-2,3-dlhydrofuran This example illustrates a preparation which can be used to prepare the 5-allylamino substituted compounds of the invention.
~S3;~'7 ~1 -24-One gram of sodium hydroxide in 4.0 ml of water is added to a mixture of 1 mmol of 2-(thien 2-yll-3-oxo-4-05 (3 trifluoromethylphenyl)-5-amino-2,3-dihydrofuran in 80 ml of methylene chloride at room temperature followed by the addition of 1 mmol of allyl bromide and 0.27 9 of benzyltriethylammonium chloride The resulting mixture is stirred at room temperature for about 18 hours after which time it can be washed three times with water, dried over magnesium sulfate and concentrated in vacuo. The residue can ~e purified by chromatography over silica gel to yield the title compound.
Similarly, by applying this procedure to the products listed in Examples 3 and 4, the corresporlding 5-allylamino analogs thereof can bs prepared. Similarly, by approximately doubling the amount of allyl bromide and sodium hydroxide, the corresponding 5-diallylamino analogs thereof can be prepared.
In a like manner, by using ethyl bxomide in place of allyl bromide, the corresponding 5-ethyl and 5-diethyl analogs can be prepared.
Similarlyl by using the 5-methylamino analogs of Example 4 as starting materials, the corresponding 5-N-methyl-N-allylamino and 5-N-methyl-N-ethyl analogs can be prepared.
~ ~e~
Lithium salt of 2-thien 2-yl-3-oxo-4-(3-trifluoromethylphenyl)- `
5-methylamino-2,3-dihydrofuran (R~ R2-Li) This example illustrates a preparation which can be used to prepare the lithium salts of the invention.
In this example, 5.4 ml of 1.6M n-butyllithium in hexane i5 added dropwise to a stirred solution contain-ing 2.al 9 of 2-thien-2-yl-3-oxo-4-(3-trifluoromethyl-phenyl)-5 amino-2,3-dihydrofuran in 25 ml of tetrahydro-furan at -30C. The mixture is stirred for 20 minutes and can ~hen be concentrated by evaporation ln vacuo to yield the title compound.
, i! ;2~53~
01 ~-25-Similarly, by following the same procedure, the corresponding lithium salts of the compounds of 05 Examples 3-5 can bs prepared.
Example 7 The compounds listed in Table A hereinbelow were prepared using the appropriate starting materials and pro-cedures described in the Examples hereinabove.
`~ ~0 I
, ~: 35 :
~2S~3~L7 * #er ~ ~ ~ er .~ C ~, .,, o , o ~o _, ~ Ul U~
a~ ~ ~ ~r ~: , ,, ~ ~ , :, ~c ~
r~
o .....
g ~ ~r er eP ~r ~ .
., ~, Z _, ~ _, ~ _, ~
cn O ~
U~
¢ ~ ~
Z ~ ~ ~ ~ ~ ~ _, ~ ~ o . . . . .
o ~ ~ .
~ ~ Z ~C ~ O~n0~r~
c~
I ~ /Z~
/ ~ \ N r-lC O ~ ~ Lf') ~ CO
~ ~ Ln ~ t~ c~
.
f~
~ ~c s a~
s ~c s s ~
J~
3 3 ~ ~ O
~ O
ol Z I ~ ~
Ln O U- o Ul o ~7 ~ _I ~ ~
~:
3L~S5~
~l -27-~.
In this example, the compounds of Table A were 05 respecti~ely tested using the procedures described herein-below for pre-emergent and post-emergent activity against a variety of grasses and broad-leaf plants including one grain crop and one broad-leaf crop. The compounds tested are identified by compound number in Table A hereinabove.
Pre-Emergent Herbicide Test Pre-emergence herbicidal activity was determined in the following manner.
Test solutions of the respective compounds were prepared as follows:
35515 mg of test compound was dissolved in 15 m~
of acetone. 2 ml of acetone containing llO mg of a non-ionic surfactant was added to the solution. 12 ml of this stock solution was then added to 47.7 ml of water which contained the same nonionic surfactant at a concentration ~; 20 of 625 mg/l.
Seeds of the test veyetation were planted in a pot of soil and the test solution was sprayed uniformly onto the soil surface either at a dcse of 27.5 micro-grams/cm2. The pot was watered and placed in a green-house. The pot was watered intermittently and observed for seedling emergence, health of emerging seedlings, etc., for a 3-week periodO At the end of this period, the herbicidal effectiveness of the compound was rated based on the physiological observations~ A 0-to-lO0 scale was used, 0 representing no phytotoxicity, lO0 representing complete kill. The results of these tests are summarized in Table l.
Post-Emergent Herbicidal Te~t The test compound was formulated in the same manner as described above for the pre-emergent ~est.
This formulation was uniformly sprayed on 2 similar pots containing plants ~ to 3 inches tall (except wild oats, soybean and watergrass which were 3 to 4 inches tall) ~approximately 15 to 25 plants per pot) at a dose of 27.5 microgram/cm~. After the plants had dried, they were .
~2S~i3~7 placed in a greenhouse and then watered intermittsntly at their bases as needed. The plants were observed periodic-o~ ally for phytotoxic effects and physiological and morpho-logical responses to the treatment, After 3 weeks, the herbicidal effectiveness of the compound was rated based on these observations. A 0-to-100 scale was used, 0 representing no phytotoxicity, 100 representing complete kill. The results of these tests are summarized in Table 2.
Pre-Emergence Herbicidal Activity Application Rate: 27.5 micrograms/cm2, unless otherwise noted Broad~Leaf Plants Grasses Com-- % Ph~toxicity ~ 3~959~19~ ~
pound Lambs- Pig Soy Crab Water Wild : No. _ 5~ Mustarù weed bean 9~ grass Oats Rice 1 , 100 100 100100 100 100 99 g7 3 100 10~ 10090 100 100 100 100 4 100 100 100100 1~0 100 100 100 TA~LE 1 Application Rate: 27.5 micrograms/cm29 : 30 unless otherwise noted Broad-Leaf Plants Grasses Com- % Phytotoxicity_ % Phytotoxicity ~ pound Lambs- Pig Soy Crab Water Wild : No. ~uart r Mustard weed bean ~rass 9~ Oats Rice 1 ~5 9g ~8 38 45 60 65 30 ~:; 3 70 90 65 70 80 60 75 25 ~ 4 Not Test0d : 5 85 95 70 90 70 90 93 70 ::~ 4~
~;~5S3~7 As can be seen from the above Table 1, the tes~
compounds of the invention exhibited a broad spectrum of oS excellent pre-emergence phytotoxic activity. Moreover, as shown by Table 2 the compounds also exhibit a broad spec-trum of post-emergence phytotoxic activity and especially so Compound No. 2.
: Obviously, many modifications and variations of the invention described hereinabove and below can be made without departing from the essence and scope thereof.
:: 2 ~' :
':
~0 :
Claims (44)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A compound having the formula:
(I) wherein R1 and R2 are independently hydrogen, lower alkyl having 1 through 4 carbon atoms or alkenyl having 3 through 6 carbon atoms;
R3 is hydrogen, lower alkyl, lower alkoxy, halo, or trifluoromethyl and can be at any available position on the phenyl ring;
R4 is lower alkyl, lower alkoxy, halo, or trifluoromethyl;
Z is a saturated or unsaturated sulfur or oxygen heterocycle radical having 5 or 6 ring atoms one of which is sulfur or oxygen and the remainder of which are carbon atoms;
and compatible cation salts thereof.
(I) wherein R1 and R2 are independently hydrogen, lower alkyl having 1 through 4 carbon atoms or alkenyl having 3 through 6 carbon atoms;
R3 is hydrogen, lower alkyl, lower alkoxy, halo, or trifluoromethyl and can be at any available position on the phenyl ring;
R4 is lower alkyl, lower alkoxy, halo, or trifluoromethyl;
Z is a saturated or unsaturated sulfur or oxygen heterocycle radical having 5 or 6 ring atoms one of which is sulfur or oxygen and the remainder of which are carbon atoms;
and compatible cation salts thereof.
2. The compound of Claim 1 wherein R1 and R2 are independently selected from the group of hydrogen, methyl or ethyl and R3 is hydrogen.
3. The compound of Claim 2 wherein one of R1 or R2 is hydrogen and the other is hydrogen, methyl or ethyl.
4. The compound of Claim 1 wherein R3 is hydrogen.
5. The compound of Claim 2 wherein R3 is hydrogen.
6. The compound of Claim 3 wherein R3 is hydrogen.
7. The compound of Claim 1 wherein Z is a wholly unsaturated heterocycle radical or a partially unsaturated heterocycle radical having a single double bond.
8. The compound of Claim 1 wherein Z is a saturated heterocycle radical.
9. The compound of Claim 1 wherein Z has the formula wherein one or two of X, X1, and X2 are indepen-dently sulfur or oxygen and the others are carbon atoms, and the dotted line indicates that the ring can be saturated, or can have 1 or 2 double bonds.
10. The compound of Claim 1 wherein Z has the formula wherein one or two of X, X1, X2 and X3 is oxygen or sulfur and the others are carbon atoms and the dotted line indicates the ring can be saturated or can have 1 or 2 double bonds.
11. The compound of Claim 6 wherein Z is thienyl.
12. The compound of Claim 6 wherein Z is furyl.
13. The compound of Claim 6 wherein Z is thiopyranyl or pyranyl.
14. The compound of Claim 1 wherein said compound is selected from the group having the formula:
wherein R1, R2, R3 and Z are as defined in Claim 1;
and compatible cation salts thereof.
wherein R1, R2, R3 and Z are as defined in Claim 1;
and compatible cation salts thereof.
15. The compound of Claim 14 wherein R1 and R2 are independently hydrogen, methyl or ethyl and R3 is hydrogen and compatible cation salts thereof.
16. The compound of Claim 15 wherein one of R1 or R2 is hydrogen and the other is hydrogen, methyl or ethyl and compatible cation salts thereof.
17. The compound of Claim 16 wherein Z is thienyl.
18. The compound of Claim 16 wherein Z is furyl.
19. The compound of Claim 16 wherein Z is dihydro-thienyl or dihydrofuryl.
20. The compound of Claim 16 wherein Z is tetra-hydrothienyl or tetrahydrofuryl.
21. The compound of Claim 16 wherein Z is thio-pyranyl.
22. The compound of Claim 16 wherein Z is pyranyl.
23. The compound of Claim 16 wherein Z is dihydropyranyl or dihydrothiopyranyl.
24. The compound of Claim 16 wherein Z is tetrahydro-pyranyl or dihydrothiopyranyl.
25. The compound of Claim 16 wherein Z is thien-2-yl and one of R1 or R2 is hydrogen or a compatible cation and the other is hydrogen, methyl or ethyl.
26. The compound of Claim 25 wherein one of R1 or R2 is hydrogen or a compatible cation and the other is methyl.
27. The compound of Claim 25 wherein one of R1 or R2 is hydrogen or a compatible cation and the other is ethyl.
28. The compound of Claim 25 wherein R1 and R2 are independently hydrogen or a compatible cation.
29. The compound of Claim 16 wherein Z is thien-3-yl; R3 is hydrogen, and one of R1 or R2 is hydrogen or a compatible cation and the other is methyl.
30. The compound of Claim 16 wherein Z is fur-2-yl or fur-3-yl; R3 is hydrogen and one of R1 or R2 is hydrogen or a compatible cation and the other is methyl.
31. The compound of Claim 14 wherein R3 is hydrogen.
32. A herbicidal composition comprising a herbicidally effective amount of the compound of Claim 1, or mixtures of such compounds, and a compatible carrier.
33. A herbicidal composition comprising a herbicidally effective amount of the compound of Claim 25, or mixtures thereof, and a compatible carrier.
34. A method for preventing or destroying plants which comprises applying a herbicidally effective amount of the compound of Claim 1, or mixtures thereof, to the foliage or potential growth medium of said plants.
35. A method for preventing or destroying plants which comprises applying a herbicidally effective amount of the compound of Claim 25, or mixtures thereof, to the foliage or potential growth medium of said plants.
36. A plant growth regulating composition which comprises an amount of the compound of Claim 1, or mixtures thereof, effective to alter the growth pattern of plants.
37. A method for regulating the growth of plants which comprises applying to the foliage of said plants or their growth medium an amount of the compound of Claim 1, or mixtures thereof, effective to alter the growth pattern of such plants.
38. The compound of Claim 1 wherein Z is thien-2-yl.
39. The compound of Claim 1 wherein Z is thien-3-yl.
40. The compound of Claim 16 wherein Z is thien-2-yl.
41. The compound of Claim 16 wherein Z is thien-3-yl.
42. The compound of Claim 16, wherein Z is thienyl, furyl, pyranyl or thiopyranyl.
43. A herbicidal composition comprising a herbicidally efiective amount of the compound of Claim 43, or mixtures thereof, and a compatible carrier.
44. A method for preventing or destroying plants which comprises applying a herbicidally effective amount of the compound of Claim 43, or mixtures thereof, to the foliage or potential growth medium of said plants.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000489238A CA1255317A (en) | 1985-08-22 | 1985-08-22 | Herbicidal 2-(oxa or thia heterocycle)5-amino-3-oxo-4- (substituted-phenyl)-2,3-dihydrofurans |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CA000489238A CA1255317A (en) | 1985-08-22 | 1985-08-22 | Herbicidal 2-(oxa or thia heterocycle)5-amino-3-oxo-4- (substituted-phenyl)-2,3-dihydrofurans |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1255317A true CA1255317A (en) | 1989-06-06 |
Family
ID=4131230
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA000489238A Expired CA1255317A (en) | 1985-08-22 | 1985-08-22 | Herbicidal 2-(oxa or thia heterocycle)5-amino-3-oxo-4- (substituted-phenyl)-2,3-dihydrofurans |
Country Status (1)
| Country | Link |
|---|---|
| CA (1) | CA1255317A (en) |
-
1985
- 1985-08-22 CA CA000489238A patent/CA1255317A/en not_active Expired
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