WO2000024722A1 - 2,3-dihydro-4-oxo-4h-1,3-oxazine and 2-oxo-1,2,5,6-tetrahydropyridine derivatives and their use as herbicides - Google Patents

2,3-dihydro-4-oxo-4h-1,3-oxazine and 2-oxo-1,2,5,6-tetrahydropyridine derivatives and their use as herbicides Download PDF

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Publication number
WO2000024722A1
WO2000024722A1 PCT/EP1999/008305 EP9908305W WO0024722A1 WO 2000024722 A1 WO2000024722 A1 WO 2000024722A1 EP 9908305 W EP9908305 W EP 9908305W WO 0024722 A1 WO0024722 A1 WO 0024722A1
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Prior art keywords
compound
alkyl
methyl
oxo
dihydro
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PCT/EP1999/008305
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French (fr)
Inventor
Nicholas Charles Ray
Michael Abbott
Yoshihiro Usui
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Aventis Cropscience S.A.
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Priority to AU12678/00A priority Critical patent/AU1267800A/en
Publication of WO2000024722A1 publication Critical patent/WO2000024722A1/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
    • C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
    • C07D265/06—1,3-Oxazines; Hydrogenated 1,3-oxazines not condensed with other rings
    • C07D265/08—1,3-Oxazines; Hydrogenated 1,3-oxazines not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
    • C07D265/10—1,3-Oxazines; Hydrogenated 1,3-oxazines not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with oxygen atoms directly attached to ring carbon atoms
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/72—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms
    • A01N43/86—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with nitrogen atoms and oxygen or sulfur atoms as ring hetero atoms six-membered rings with one nitrogen atom and either one oxygen atom or one sulfur atom in positions 1,3

Definitions

  • the present invention relates to novel cyclic amide derivatives , compositions containing them, processes for herbicides their 5 preparation , and their use as .
  • X represents -S(0) v -, an oxygen atom or -NR 12 ;
  • Y represents -O- or -CH2-;
  • 15 R! represents phenyl, benzyl or thienyl optionally substituted by one to five groups which may be the same or different selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0) n R 6 , -CO2R 6 , -COR 6 , cyano, 20 nitro, -O (CH2 ) q ⁇ C02R 6 and phenoxy; or alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl or cycloalkyl;
  • R 3 represents CO HR 9 , COR 10 ; C0 2 R 1:L ; or phenyl optionally substituted by one to five groups which may be the same or different selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) n R 6 , ' -C0 2 R 6 , -COR 6 , cyano, nitro, -0 (CH2 ) q ⁇ C02R 6 and phenoxy;
  • R ⁇ and R5 independently represent alkyl;
  • R 6 represents alkyl or haloalkyl;
  • R 7 and R 8 independently represent hydrogen, alkyl or haloalkyl ;
  • R9 represents phenyl optionally substituted by from one to five groups which may be the same or different selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0) n R 6 , -CO2R 6 , -COR 6 , cyano, nitro, -NR 7 R 8 , phenoxy, -0(CH 2 ) q C0 2 R 6 and -SF 5 ;
  • -CH 2 OR 17 -CH 2 OCOR 17 , -CH2 ⁇ S0 2 R 17 and alkenyl
  • a phenyl ring optionally substituted by from one to four groups which may be the same or different selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0) n R 6 , CN and NO2 , and which is fused to a second five or six membered cycloalkyl or cycloalkenyl ring, or to a saturated five or six membered heterocyclic ring (for example to give a 1,3- benzodioxole or 1, 4-benzodioxane ring) which contains one to three heteroatoms which may be the same or different selected from nitrogen, oxygen and sulphur, said ring systems being optionally substituted by one or more groups R 19 or optionally one of the carbon atoms in the cycloalkyl, cycloalkeny
  • R 12 represents hydrogen, alkyl, haloalkyl, alkenyl , haloalkenyl , alkynyl , haloalkynyl or cycloalkyl;
  • R 13 , R 14 , R 15 and R 16 independently represent hydrogen, alkyl or haloalkyl;
  • R 17 represents phenyl optionally substituted by one or more groups which may be the same or different selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0) n R 6 , cyano and nitro;
  • R 18 represents alkyl or haloalkyl
  • R ⁇ 9 represents halogen, alkyl or haloalkyl
  • R 20 represents cycloalkyl containing from three to seven carbon atoms optionally substituted by one or more groups R 19 ;
  • R 21 represents cycloalkyl containing from three to seven carbon atoms or cycloalkenyl containing five or six carbon atoms, wherein the ring systems are optionally substituted by one or more groups R 19 ;
  • R 22 and R 23 represent alkyl or the group -CH(0R 22 ) (OR 23 ) - represents a five or six membered cyclic acetal, namely a 1, 3-dioxolane or 1,3-dioxane ring of formula -CH(OR 22a ) (OR 23a )- wherein R 2 2a and R23a together represent a C2 or C3 alkylene chain which is optionally substituted by alkyl or haloalkyl ;
  • R 2 ⁇ represents cycloalkyl containing from three to seven carbon atoms optionally substituted by one or more groups R ⁇ 9 ; m, n, p, t, u and v represent zero, one or two; q represents one or two ; r and s represent zero or one; or an agriculturally acceptable salt thereof.
  • 'agriculturally acceptable salts means salts the cations or anions of which are known and accepted in the art for the formation of salts for agricultural or horticultural use.
  • the salts are water-soluble.
  • Suitable salts with bases include alkali metal (e.g. sodium and potassium), alkaline earth metal (e.g. calcium and magnesium) , ammonium and amine (e.g. diethanolamine, triethanolamine, octylamine, morpholine and dioctylmethylamine) salts.
  • Suitable acid addition salts e.g. formed by compounds of formula (I) containing an amino group, include salts with inorganic acids, for example hydrochlorides , sulphates , phosphates and nitrates and salts with organic acids for example acetic acid.
  • alkyl groups and alkyl moieties contain from one to six carbon atoms and are straight- or branched- chain; alkenyl groups and alkenyl moieties contain from two to six carbon atoms and are straight- or branched-chain; alkynyl groups and alkynyl moieties contain from two to six carbon atoms and are straight- or branched-chain; cycloalkyl groups contain from 3 to 7 carbon atoms in the ring; and halogen means fluorine, chlorine, bromine or iodine.
  • R 1 represents phenyl optionally substituted by one to three groups which may be the same or different selected from halogen, alkyl and haloalkyl; or represents alkyl or haloalkyl are preferred (compounds in which R 1 represents alkyl or haloalkyl are especially preferred) .
  • Compounds of formula (I) above in which R represents alkyl, haloalkyl or cycloalkyl are also preferred (compounds in which R represents i-propyl, sec-butyl, tert-butyl, 2,2- dimethylpropyl, 2 , 2 , 2-trifluoroethyl or cyclopentyl are especially preferred) .
  • R 2 represents hydrogen, alkyl or haloalkyl
  • P. 2 represents hydrogen, methyl or ethyl.
  • R 2 represents methyl.
  • R 3 represents CONHR 9 or COR 10
  • R 9 represents phenyl optionally substituted by one to three groups which may be the same or different selected from halogen, alkyl, haloalkyl and nitro
  • R 10 represents cycloalkyl containing from three to six carbon atoms or cycloalkenyl containing five or six carbon atoms, the ring systems of which are optionally substituted by a group R 19
  • R 10 represents an optionally halogenated alkyl group containing up to four carbon atoms which is substituted by cycloalkyl containing from three to six carbon atoms (the cycloalkyl ring may be optionally substituted by one or more halogen or alkyl groups)
  • R 10 represents -CH 2 - (phenyl substituted by one to three groups selected from halogen, methyl and trifluoromethyl) are especially preferred) .
  • R 3 represents CONHR 9 in which R 9 represents phenyl optionally substituted by one to four groups which may be the same or different selected from halogen, alkyl, haloalkyl, nitro and alkoxy (most pref rably R 9 represents 3-halophenyl , 2 , 5-dihalophenyl, 3 , 5-dihalo ⁇ henyl, 2-halo-5- haloalkylphenyl, 3-haloalkylphenyl or 2-halo-5- alkylphenyl) .
  • X represents -S-, -0- or NR 12 in which R 12 represents hydrogen or alkyl ; Y represents-O- ;
  • R 1 represents phenyl which is optionally substituted by one to three groups which may be the same or different selected from halogen, alkyl and haloalkyl; or represents alkyl or haloalkyl;
  • R 2 represents hydrogen, alkyl or haloalkyl
  • R 3 represents CONHR 9 in which R 9 represents phenyl optionally substituted by one to three groups which may be the same or different selected from halogen, alkyl, haloalkyl and nitro
  • R 3 represents COR 10 in which R 10 represents cycloalkyl containing from three to six carbon atoms, the ring system of which is optionally substituted by a group R 19 ; or R 1 represents an optionally halogenated alkyl group containing up to four carbon atoms which is substituted by cycloalkyl containing from three to six carbon atoms (the cycloalkyl ring is optionally substituted by one or more halogen or alkyl groups); or R 10 represents -CH 2 - (phenyl substituted by one to three groups selected from halogen, methyl and trifluorom thyl) ,- and R ⁇ and R5 represent methyl .
  • Y represents -0-;
  • R 1 represents alkyl or haloalkyl;
  • R 2 represents hydrogen, methyl or ethyl
  • R 3 represents CONHR 9 in which R 9 represents phenyl substituted by one to three groups which may be the same or different selected from halogen, methyl and trifluoromethyl
  • R 3 represents COR 10 in which R 10 represents cycloalkyl containing from three to six carbon atoms optionally substituted by alkyl; or R 10 represents an optionally halogenated alkyl group containing up to four carbon atoms which is substituted by cycloalkyl containing from three to six carbon atoms (the cycloalkyl ring may be optionally substituted by an alkyl group)
  • R ⁇ and R5 represent methyl .
  • a further more preferred class of compounds of formula (I) above are those wherein: X represents -S- ;
  • Y represents -O- ;
  • R 1 represents C2-C5 alkyl or haloalkyl, cyclopentyl, cyclohexyl, or phenyl optionally substituted by a halogen atom;
  • R 2 represents methyl;
  • R 3 represents CONHR 9 in which R 9 represents phenyl substituted by one to four groups which may be the same or different selected from halogen, methyl, halomethyl, nitro and methoxy; or R 3 represents C0 2 R l in which R 11 represents alkyl; or R 3 represents phenyl substituted by two halogen atoms ; and R ⁇ and R ⁇ represent methyl .
  • Particularly preferred compounds of formula (I) are: N- (2, 5-difluorophenyl) -2- (2 , 3-dihydro-6- methyl-4-oxo-5-phenylthio-4H-l, 3-oxazin-3-yl) -2- methylpropanamide (compound 1) ;
  • N Ph' means phenyl
  • ⁇ e' means methyl
  • 'Et' means ethyl
  • 'Pr' means propyl
  • x iPr' means isopropyl
  • v cPr' means cyclopropyl
  • ⁇ Bu' means butyl
  • iBu' means isobutyl
  • ' sBu' means sec-butyl
  • tBu' means tert-butyl
  • l cBu' means cyclobutyl
  • 'cPe' means cyclopentyl
  • cHex' means cyclohexyl.
  • compounds of formula (I) wherein R , X, Y, R 2 , R 4 and R ⁇ are as defined above and R 3 is -CONHR 9 wherein R 9 is as defined above, may be prepared by the reaction of a compound of general formula (II) :
  • the reaction is generally performed in the presence of a base, for example a tertiary amine such as triethylamine and in an inert solvent such as dichloromethane at a temperature from 0°C to the reflux temperature of the solvent.
  • a base for example a tertiary amine such as triethylamine and in an inert solvent such as dichloromethane at a temperature from 0°C to the reflux temperature of the solvent.
  • compounds of formula (I) wherein R 1 , X, Y, R 2 , R 4 and R 5 are as defined above and R 3 is -CONHR 9 wherein P. 9 is as defined above, may also be prepared by the reaction of a compound of formula (IV) :
  • R 1 , X, Y, R 2 , R 4 and R 5 are as defined above, with an amine of formula (III) above wherein R 9 is as defined above, and a coupling reagent.
  • the coupling reagent is for example N,N' -dicyclohexylcarbodiimide (DCCI) .
  • the reaction is performed optionally in the presence of a base for example 4- dimethylaminopyridine (DMAP) and in an inert solvent such as dichloromethane at a temperature from 0 to 60°C.
  • a base for example 4- dimethylaminopyridine (DMAP) and in an inert solvent such as dichloromethane at a temperature from 0 to 60°C.
  • compounds of formula (I) wherein R 1 , X, Y, R , R 4 and R 5 are as defined above, and R 3 represents C0 R xl and R 11 is defined above may be prepared by the reaction of a compound of formula (II) with an alcohol of formula (V) : R xl OH (V) wherein R 1 is as defined above.
  • the reaction is generally conducted using the conditions employed for the above preparation of compounds of formula (I) wherein R 3 is -CONHR 9 from compounds of formula (II) and (III) .
  • compounds of formula (I) wherein R 1 , Y, R 2 , R 4 and R ⁇ are as defined above, R 3 is COR 1 ⁇ , and X is an oxygen atom or NR 12 wherein R 1 ⁇ and R 12 is as defined above, may be prepared by the oxidation of the corresponding compound of formula (VI) :
  • compounds of formula (I) wherein R 1 , X, R 2 , R 3 , R 4 and R 5 are as defined above and Y is an oxygen atom may be prepared by the reaction of a compound of formula (VII) :
  • R 3 , R 4 and R ⁇ are as defined above and R is an alkyl group (preferably methyl or ethyl) .
  • the reaction is generally performed in the presence or absence of solvent and at a temperature from 90°C to 200°C or the boiling point of the solvent.
  • the solvent when used is inert, for example xylene, and the acetone produced is preferably removed by distillation.
  • compounds of formula (I) wherein R 1 , X, R 2 , R 3 , R 4 and R 5 are as defined above and Y is an oxygen atom may also be prepared by the reaction of a compound of formula (IX) :
  • R 2 C(0)-CH ⁇ XR )-C0 2 R (IX) wherein R 1 , X and R 2 are as defined above and R represents an alkyl group (preferably methyl or ethyl), with an i ine of formula (VIII) wherein R 3 , R 4 and R ⁇ are as defined above.
  • the reaction is performed utilising similar conditions to those used for the preparation of compounds of formula (I) wherein Y is an oxygen atom from compounds of formula (VII) above and preferably with removal of the alcohol ROH formed in the reaction.
  • compounds of formula (I) wherein R 1 , X, R 2 , R 3 , R 4 and R 5 are as defined above and Y is -CH 2 - may be prepared by the reaction of a compound of formula (X) :
  • the base is generally an alkali metal alkoxide or carbonate such as sodium methoxide or potassium carbonate, in an inert solvent such as ethanol, or with an alkali metal hydride such as sodium hydride, in an inert solvent such as tetrahydrofuran, and at a temperature from 0°C to 100°C.
  • compounds of formula (I) in which m, n, p, t, u or v represent one or two may be prepared by the oxidation of the sulphur atom of the corresponding compounds in which m, n, p, t, u or v represent zero or one.
  • the oxidation of the sulphur atom is generally carried out using for example 3-chloroperbenzoic acid in an inert solvent such as dichloromethane at a temperature from -40°C to room temperature.
  • Compounds of formula (I) above may be prepared by interconversion of other compounds of formula (I) and such conversions constitute further features of the present invention. Examples of such processes are known in the art, for example as described in International Patent Publication Number 97/00865.
  • Acid chlorides of formula (II) may be prepared by the reaction of the corresponding acids of formula (IV) above with a chlorinating agent, for example oxalyl chloride or a mixture of triphenylphosphine and carbon tetrachloride .
  • a chlorinating agent for example oxalyl chloride or a mixture of triphenylphosphine and carbon tetrachloride .
  • the reaction with oxalyl chloride may be performed in an inert solvent for example dichloromethane optionally in the presence of a catalyst, for example N,N-dimethylformamide, at a temperature from 0 to 50°C.
  • the reaction with triphenylphosphine and carbon tetrachloride may be performed in an inert solvent, for example toluene or excess carbon tetrachloride, and at a temperature from 20 to 120°C.
  • Carboxylic acids of formula (IV) may be prepared by the hydrolysis of an ester of formula (XI) :
  • R 1 , X, Y, R 2 , R 3 , R 4 and R 5 are as defined above and R represents an alkyl group, preferably methyl or ethyl (i.e. a compound of formula (I) in which R 3 represents C0 R 11 and R 11 represents alkyl) .
  • the reaction is generally performed in the presence of a base for example sodium or potassium hydroxide and in a solvent, e.g. aqueous alcohol at a temperature from 0°C to the reflux temperature of the solvent.
  • reaction may be performed using an acid such as trifluoroacetic acid in a solvent such as dichloromethane optionally in the presence of water at a temperature from 0°C to 50°C.
  • organometallic reagent of formula R ⁇ 0-M, wherein R 1 ⁇ is as defined above and M is a metallic group, preferably a magnesium bromide group or a lithium atom.
  • the reaction is generally performed in an inert solvent such as ether or tetrahydrofuran and at a temperature of from -78°C to the reflux temperature of the solvent.
  • R X SH (XV) The reaction is generally performed in a solvent such as an alcohol, for example iso- propanol, in the presence of a base, for example a tertiary amine such as triethylamine, and at a temperature of from 0°C to 100°C.
  • a solvent such as an alcohol, for example iso- propanol
  • a base for example a tertiary amine such as triethylamine
  • R are as defined above, R 2 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl, and X is -NR 12 , may be prepared by the reaction of the corresponding ketoester of formula (XIV) with an amine of formula (XVII) :
  • reaction is generally conducted with or without a solvent, optionally in the presence of a base such as a trialkylamine for example triethylamine, at a temperature of from 0°C to 150°C.
  • a base such as a trialkylamine for example triethylamine
  • compositions suitable for herbicidal use comprising one or more of the cyclic amide derivatives of formula I or an agriculturally acceptable salt thereof, in association with, and preferably homogeneously dispersed in, one or more compatible agriculturally- acceptable diluents or carriers and/or surface active agents [i.e. diluents or carriers and/or surface active agents of the type generally accepted in the art as being suitable for use in herbicidal compositions and which are compatible with compounds of formula I] .
  • the term "homogeneously dispersed” is used to include compositions in which the compounds of formula I are dissolved in other components.
  • compositions are used in a broad sense to include not only compositions which are ready for use as herbicides but also concentrates which must be diluted before use.
  • the compositions contain from 0.05 to 90% by weight of one or more compounds of formula I.
  • the herbicidal compositions may contain both a diluent or carrier and surface-active (e.g. wetting, dispersing, or emulsifying) agent.
  • Surface-active agents which may be present in herbicidal compositions of the present invention may be of the ionic or non-ionic types, for example sulphoricinoleates, quaternary ammonium derivatives, products based " on condensates of ethylene oxide with alkyl and polyaryl phenols, e.g.
  • nonyl- or octyl-phenols or carboxylic acid esters of anhydrosorbitols which have been rendered soluble by etherification of the free hydroxy groups by condensation with ethylene oxide, alkali and alkaline earth metal salts of sulphuric acid esters and sulphonic acids such as dinonyl- and dioctyl-sodium sulphonosuccinates and alkali and alkaline earth metal salts of high molecular weight sulphonic acid derivatives such as sodium and calcium lignosulphonates and sodium and calcium alkylbenzene sulphonates .
  • the herbicidal compositions according to the present invention may comprise up to 10% by weight, e.g. from 0.05% to 10% by weight, of surface-active agent but, if desired, herbicidal compositions according to the present invention may comprise higher proportions of surface-active agent, for example up to 15% by weight in liquid emulsifiable suspension concentrates and up to 25% by weight in liquid water soluble concentrates .
  • suitable solid diluents or carriers are aluminium silicate, microfine silicon dioxide, talc, chalk, calcined magnesia, kieselguhr, tricalcium phosphate, powdered cork, adsorbent carbon black and clays such as kaolin and bentonite.
  • the solid compositions (which may take the form of dusts, granules or wettable powders) are preferably prepared by grinding the compounds of formula I with solid diluents or by impregnating the solid diluents or carriers with solutions of the compounds of formula I in volatile solvents, evaporating the solvents and, if necessary, grinding the products so as to obtain powders .
  • Granular formulations may be prepared by absorbing the compounds of formula I (dissolved in suitable solvents, which may, if desired, be volatile) onto the solid diluents or carriers in granular form and, if desired, evaporating the solvents, or by granulating compositions in powder form obtained as described above.
  • Solid herbicidal compositions particularly wettable powders and granules, may contain wetting or dispersing agents (for example of the types described above) , which may also, when solid, serve as diluents or carriers.
  • Liquid compositions according to the invention may take the form of aqueous, organic or aqueous-organic solutions, suspensions and emulsions which may incorporate a surface-active agent.
  • Suitable liquid diluents for incorporation in the liquid compositions include water, glycols, glycol ethers, tetrahydrofurfuryl alcohol, acetophenone, cyclohexanone, isophorone, N-alkyl pyrrolidones, toluene, xylene, mineral, animal and vegetable oils, esterified vegetable oils and light aromatic and naphthenic fractions of petroleum (and mixtures of these diluents).
  • Surface-active agents which may be present in the liquid compositions, may be ionic or non-ionic (for example of the types described above) and may, when liquid, also serve as diluents or carriers.
  • Powders, dispersible granules and liquid compositions in the form of concentrates may be diluted with water or other suitable diluents, for example mineral or vegetable oils, particularly in the case of liquid concentrates in which the diluent or carrier is an oil, to give compositions ready for use.
  • suitable diluents for example mineral or vegetable oils, particularly in the case of liquid concentrates in which the diluent or carrier is an oil, to give compositions ready for use.
  • liquid compositions of the compound of formula I may be used in the form of self-emulsifying concentrates containing the active substances dissolved in the emulsifying agents or in solvents containing emulsifying agents compatible with the active substances, the simple addition of such concentrates to water producing compositions ready for use.
  • Liquid concentrates in which the diluent or carrier is an oil may be used without further dilution using the electrostatic spray technique.
  • Herbicidal compositions according to the present invention may also contain, if desired, conventional adjuvants such as adhesives, protective colloids, thickeners, penetrating agents, spreading agents, stabilisers, sequestering agents, anti-caking agents, colouring agents and corrosion inhibitors. These adjuvants may also serve as carriers or diluents .
  • Herbicidal compositions according to the present invention may also comprise the compounds of formula I in association with, and preferably homogeneously dispersed in, one or more other pesticidally active compounds and, if desired, one or more compatible pesticidally acceptable diluents or carriers, surface-active agents and conventional adjuvants as hereinbefore described.
  • insecticides e.g. synthetic pyrethroids, e.g. permethrin and cypermethrin
  • fungicides e.g. carbamates, e.g. methyl
  • Pesticidally active compounds and other biologically active materials which may be included in, or used in conjunction with, the herbicidal compositions of the present invention, for example those hereinbefore mentioned, and which are acids, may, if desired, be utilized in the form of conventional derivatives, for example alkali metal and amine salts and esters.
  • a suspension concentrate is formed from: Compound of formula (I) 20% Ethylan BCP (surfactant) 0.5%
  • Rhodorsil 426R Antifoaming agent
  • Propylene glycol antifreeze
  • Atagel 50 anti-settling agent
  • Similar suspension concentrates may be prepared by replacing Compound 1 with other cyclic amide derivatives of formula I .
  • An emulsion concentrate is formed from the following: Compound of formula 1 10%
  • Synperonic NPE1800 Surfactant
  • Arylan CA Surfactant
  • NMP N-methylpyrrolidone
  • a wettable powder is formed from the following :
  • Similar wettable powders may be prepared by replacing Compound 1 with other cyclic amide derivatives of formula I.
  • a method for controlling the growth of weeds i.e. undesired vegetation
  • a method for controlling the growth of weeds i.e. undesired vegetation
  • the cyclic amide derivatives are normally used in the form of herbicidal compositions (i.e. in association with compatible diluents or carriers and/or surface active agents suitable for use in herbicidal compositions), for example as hereinbefore described.
  • the compounds of formula I show herbicidal activity against dicotyledonous (i.e. broad- leafed) and monocotyledonous (e.g. grass) weeds by pre- and/or post-emergence application.
  • pre-emergence application application to the soil in which the weed seeds or seedlings are present before emergence of the weeds above the surface of the soil.
  • post-emergence application application to the aerial or exposed portions of the weeds which have emerged above the surface of the soil.
  • the compounds of formula I may be used to control the growth of: broad-leafed weeds, for example, Abutilon theophrasti, Amaranthus retroflexus, Bidens pilosa, Chenopodium album, Galium aparine, Ipomoea spp . e.g.
  • Ipomoea purpurea Lindernia procumbens , Monochoria vaginalis, Sesbania exaltata, Sinapis arvensis, Solanum nigrum and Xanthium strumarium, and grass weeds, for example Alopecurus myosuroides , Avena fatua, Digitaria sanguinalis, Echinochloa crus-galli, Echinochloa oryzicola, Eleusine indica and Setaria sp , e.g. Setaria faberii or Setaria viridis, and sedges, for example, Cyperus esculentus and Scirpus juncoides.
  • the amounts of compounds of formula I applied vary with the nature of the weeds, the compositions used, the time of application, the climatic and edaphic conditions and (when used to control the growth of weeds in crop-growing areas) the nature of the crops.
  • the rate of application should be sufficient to control the growth of weeds without causing substantial permanent damage to the crop .
  • application rates between 1 g and 1000 g of active material per hectare give good results. However, it is to be understood that higher or lower application rates may be used, depending upon the particular problem of weed control encountered.
  • the compounds of formula I may be used to control selectively the growth of weeds, for example to control the growth of those species hereinbefore mentioned, by pre- or post- emergence application in a directional or non- directional fashion, e.g. by directional or non- directional spraying, to a locus of weed infestation which is an area used, or to be used, for growing crops, for example cereals, e.g. wheat, barley, oats, maize and rice, soya beans, field and dwarf beans, peas, lucerne, cotton, peanuts, flax, onions, carrots, cabbage, oilseed rape, sunflower, sugar beet, and permanent or sown grassland before or after sowing of the crop or before or after emergence of the crop.
  • cereals e.g. wheat, barley, oats, maize and rice, soya beans, field and dwarf beans, peas, lucerne, cotton, peanuts, flax, onions, carrots, cabbage, oilseed rape
  • the compounds of the invention are especially useful for controlling grass weed species .
  • the compounds of the invention are also useful for the control of weeds in rice crops grown in paddy field water.
  • the compounds of formula (I) may for example be added to the paddy field water .
  • the compounds of formula I may also be used to control the growth of weeds, especially those indicated above, by pre- or post-emergence application in established orchards and other tree-growing areas, for example forests, woods and parks, and plantations, e.g. sugar cane, oil palm and rubber plantations .
  • plantations e.g. sugar cane, oil palm and rubber plantations .
  • they may be applied in a directional or non- directional fashion (e.g. by directional or non- directional spraying) to the weeds or to the soil in which they are expected to appear, before or after planting of ' the trees or plantations at application rates between 50 g and 2000 g, and preferably between 50 g and 1000 g, most preferably between 100 g and 500 g of active material per hectare.
  • the compounds of formula I may also be used to control the growth of weeds, especially those indicated above, at loci which are not crop- growing areas but in which the control of weeds is nevertheless desirable.
  • non-crop-growing areas include airfields, industrial sites, railways, roadside verges, the verges of rivers, irrigation and other waterways, scrublands and fallow or uncultivated land, in particular where it is desired to control the growth of weeds in order to reduce fire risks.
  • the active compounds When used for such purposes in which a total herbicidal effect is frequently desired, the active compounds are normally applied at dosage rates higher than those used in crop-growing areas as hereinbefore described. The precise dosage will depend upon the nature of the vegetation treated and the effect sought.
  • Pre- or post-emergence application and preferably pre-emergence application, in a directional or non-directional fashion (e.g. by directional or non-directional spraying) at application rates between 50 g and 2000 g, and preferably between 50 g and 1000 g, most preferably between 100 g and 500 g of active material per hectare are particularly suitable for this purpose .
  • the compounds of formula I may be incorporated into the soil in which the weeds are expected to emerge. It will be appreciated that when the compounds of formula I are used to control the growth of weeds by post-emergence application, i.e.
  • the compounds of formula I will also normally come into contact with the soil and may also then exercise a pre-emergence control on later-germinating weeds in the soil. Where especially prolonged weed control is required, the application of the compounds of formula I may be repeated if required.
  • Paddy post-emergence application in greenhouse Paddy field soil was filled in 170 cm ⁇ plastic pots, a suitable amount of water and chemical fertilisers were added thereto and kneaded to convert it to a state of a paddy.
  • Paddy rice plants variety; Koshihikari
  • Paddy rice plants that had been grown in advance in a greenhouse to a stage of two leaves, were transplanted to each pot (two seedlings per pot) .
  • solutions were prepared in 100% acetone using compounds described in the Examples so that they contained active ingredients in an amount equivalent to 75, 300 and 1200 g/ha.
  • the solutions were applied to the water by dropping with a pipette.

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Abstract

The invention relates to compounds of formula (I), wherein X represents -S(O)v-, an oxygen atom or -NR12; Y represents -O- or -CH2-; R1 represents phenyl, benzyl or thienyl optionally substituted by one to five groups which may be the same or different selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(O)¿n?R?6, -CO¿2R?6, -COR6¿, cyano, nitro, -O(CH¿2?)q-CO2R?6¿ and phenoxy; or alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl or cycloalkyl; R2 represents hydrogen, alkyl, haloalkyl, alkoxyalkyl, haloalkoxyalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl, alkoxyalkenyl, -CHO, -COR6, -CO2R6, -CH2NO2, cyano, -CO2H, -COSR?6, -CONR7R8¿, -CH=NOH, -CH=NOR6, -CH=NOCOR6, -CH=NNR?7R8, -CH¿2CN, -CH2NO2 or oxiranyl; or alkyl which is substituted by a group selected from -S(O)nR6, OH, -OCOR?6, -NR7R8¿ and azido; R3 represents CONHR?9, COR10; CO¿2R11; or phenyl optionally substituted by one to five groups which may be the same or different selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(O)¿n?R?6, -CO¿2R?6, -COR6¿, cyano, nitro, -O(CH¿2?)q-CO2R?6¿ and phenoxy; R?4 and R5¿ independently represent alkyl; and to their use as herbicides.

Description

2,3-DIHYDRO-4-OXO-4H-l,3-OXAZINE AND 2-OXO-l,2,5,6-TETRAHYDROPYRIDINE DERIVAΗVES AND THEIR USE AS HERBICIDES
The present invention relates to novel cyclic amide derivatives , compositions containing them, processes for herbicides their 5 preparation , and their use as .
According to the present invention , there are provided cyclic amide derivatives o f formula ( I ) :
Figure imgf000003_0001
10 ( I ) wherein :
X represents -S(0)v-, an oxygen atom or -NR12 ;
Y represents -O- or -CH2-; 15 R! represents phenyl, benzyl or thienyl optionally substituted by one to five groups which may be the same or different selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, -CO2R6, -COR6, cyano, 20 nitro, -O (CH2 ) q~C02R6 and phenoxy; or alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl or cycloalkyl;
R2 represents hydrogen, alkyl, haloalkyl, alkoxyalkyl , haloalkoxyalkyl , alkenyl , 25 haloalkenyl, alkynyl, haloalkynyl, alkoxyalkenyl, -CHO, -COR6, -C02R6, -CH2N02, cyano, -C02H, -COSR6 , -CONR7R8, -CH=NOH, -CH=NOR6, -CH=NOCOR6, -CH=NNR7R8, -CH CN, -CH2NO2 or oxiranyl; or alkyl which is 30 substituted by a group selected from -S(0)nR6, OH, -OCOR6, -NR7R8 and azido;
R3 represents CO HR9 , COR10; C02R1:L; or phenyl optionally substituted by one to five groups which may be the same or different selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, -S (O) nR6 , '-C02R6 , -COR6, cyano, nitro, -0 (CH2 ) q~C02R6 and phenoxy;
R^ and R5 independently represent alkyl; R6 represents alkyl or haloalkyl;
R7 and R8 independently represent hydrogen, alkyl or haloalkyl ;
R9 represents phenyl optionally substituted by from one to five groups which may be the same or different selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, -CO2R6, -COR6, cyano, nitro, -NR7R8 , phenoxy, -0(CH2)qC02R6 and -SF5;
R10 represents - (CR13R14 ) r- (phenyl or naphthyl optionally substituted by from one to five groups which may be the same or different selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, -CO2 6, -COR6, cyano, nitro, -0 (CH2 ) qCθ2R6 , phenoxy, -SF5, -0C0R6, NR15R16, HR17 , -CH2NR15R16, -CONR15R16, -CONHR17, -OS0 R6 , -OS02R17 , -OCOR17, -OCH2COR17, -OCH2R17, -S(0)mR17, R17 , -P(=0) (OR6) (OR18) , -P(=0) (OR6)R18 , -CH2P(=0) (OR6) (OR18) , -CH2P(=0) (OR6)R18, -C02R17, -CH2S(0)nR6, -CH2S (0)mR17 , -CH2OR6,
-CH2OR17, -CH2OCOR17, -CH2θS02R17 and alkenyl) ; or represents a phenyl ring optionally substituted by from one to four groups which may be the same or different selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, CN and NO2 , and which is fused to a second five or six membered cycloalkyl or cycloalkenyl ring, or to a saturated five or six membered heterocyclic ring (for example to give a 1,3- benzodioxole or 1, 4-benzodioxane ring) which contains one to three heteroatoms which may be the same or different selected from nitrogen, oxygen and sulphur, said ring systems being optionally substituted by one or more groups R19 or optionally one of the carbon atoms in the cycloalkyl, cycloalkenyl or saturated five or six membered heterocyclic ring may form a carbonyl group (for fused ring systems it is the phenyl ring which is linked to the carbonyl group which forms part of -C(=O)R10); or represents a phenanthrene or anthracene ring optionally substituted by one or more groups selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, CN and N0 ; or represents - (CH2 ) s- ( five to seven membered heteroaromatic ring having from one to four ring heteroatoms which may be the same or different selected from nitrogen, oxygen and sulphur, said ring being optionally fused to a phenyl ring or to a second five to seven membered heteroaromatic ring having from one to four heteroatoms which may be the same or different selected from nitrogen, oxygen and sulphur, to form a bicyclic ring system, the monocyclic ring or either ring in the bicyclic system being optionally substituted by from one to four groups which may be the same or different selected from halogen, hydroxy, alkyl, cyano, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, -C0 R6 , -COR6, nitro, -0 (CH2 ) qC02R6 and phenoxy) ; or represents cycloalkyl containing from three to eight carbon atoms or cycloalkenyl containing four to eight carbon atoms, wherein the ring systems are optionally substituted by one or more groups selected from R19, C02H, C02R6, alkenyl, haloalkenyl, R1 , alkoxy, haloalkoxy, S(0)nR6, COR6, COR17, CH2COR17, COCH2R17 , C02CH2R17, S(0)mR17, CN, S(0)tCH2R17, S(0)uR20,
CH20R6, CHO, COR21, CONHR17, C0NR6R17 , CH2OH, -CH(0R22) (OR23 ) (optionally the group -CH(0R22) (OR2 ) represents a five or six membered cyclic acetal optionally substituted by one or more R6 groups) , or o*ne of the cycloalkyl carbon atoms forms part of a carbonyl group; or represents cycloalkyl containing from five to seven carbon atoms or cycloalkenyl containing five or six carbon atoms, the ring systems of which are optionally substituted by one or more groups R19, and wherein the ring systems are fused to a phenyl ring (for example indanyl) optionally substituted by from one to four groups which may be the same or different selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, cyano or nitro (for fused ring systems it is the cycloalkyl or cycloalkenyl ring which is linked to the carbonyl group which forms part of the -C(=0)R10 group) ; or represents alkyl, haloalkyl, alkenyl, haloalkenyl or alkynyl which are optionally substituted by one or more groups selected from -OH, -OR6, -S(0)nR6, -S(0)mR17, -C02R6 , -C02CH2R17, CN, N02, CHO, COR6, COR17, C0CH2R17 , -C02H, -C0NR15R16, -S(0) tCH2R17, -S(0)pR24, R17 # a three to six membered cycloalkyl ring optionally substituted by one or more R19 groups, a five or six membered cyclic acetal group optionally substituted by one or more R6 groups, and a thienyl or furyl ring optionally substituted by one or more groups R1^ • R11 represents alkyl, haloalkyl, cycloalkyl; or phenyl optionally substituted by one or more groups selected from halogen, alkyl and haloalkyl ;
R12 represents hydrogen, alkyl, haloalkyl, alkenyl , haloalkenyl , alkynyl , haloalkynyl or cycloalkyl;
R13, R14, R15 and R16 independently represent hydrogen, alkyl or haloalkyl; R17 represents phenyl optionally substituted by one or more groups which may be the same or different selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, cyano and nitro;
R18 represents alkyl or haloalkyl;
Rχ9 represents halogen, alkyl or haloalkyl;
R20 represents cycloalkyl containing from three to seven carbon atoms optionally substituted by one or more groups R19;
R21 represents cycloalkyl containing from three to seven carbon atoms or cycloalkenyl containing five or six carbon atoms, wherein the ring systems are optionally substituted by one or more groups R19;
R22 and R23 represent alkyl or the group -CH(0R22) (OR23 ) - represents a five or six membered cyclic acetal, namely a 1, 3-dioxolane or 1,3-dioxane ring of formula -CH(OR22a) (OR23a)- wherein R22a and R23a together represent a C2 or C3 alkylene chain which is optionally substituted by alkyl or haloalkyl ;
R2^ represents cycloalkyl containing from three to seven carbon atoms optionally substituted by one or more groups Rχ9; m, n, p, t, u and v represent zero, one or two; q represents one or two ; r and s represent zero or one; or an agriculturally acceptable salt thereof.
It will be appreciated that certain substituents in the compounds of formula (I) may contribute to optical and/or stereoisomerism.
All such forms and mixtures thereof are embraced by the present invention. In this patent specification it is to be understood that the term 'agriculturally acceptable salts ' means salts the cations or anions of which are known and accepted in the art for the formation of salts for agricultural or horticultural use. Preferably the salts are water-soluble. Suitable salts with bases include alkali metal (e.g. sodium and potassium), alkaline earth metal (e.g. calcium and magnesium) , ammonium and amine (e.g. diethanolamine, triethanolamine, octylamine, morpholine and dioctylmethylamine) salts. Suitable acid addition salts, e.g. formed by compounds of formula (I) containing an amino group, include salts with inorganic acids, for example hydrochlorides , sulphates , phosphates and nitrates and salts with organic acids for example acetic acid.
In this specification and accompanying claims unless otherwise specified, alkyl groups and alkyl moieties contain from one to six carbon atoms and are straight- or branched- chain; alkenyl groups and alkenyl moieties contain from two to six carbon atoms and are straight- or branched-chain; alkynyl groups and alkynyl moieties contain from two to six carbon atoms and are straight- or branched-chain; cycloalkyl groups contain from 3 to 7 carbon atoms in the ring; and halogen means fluorine, chlorine, bromine or iodine.
Compounds of formula (I) above in which X represents -S(0)v- and v represents zero are especially preferred because of their activity.
Compounds of formula (I) above in which R1 represents phenyl optionally substituted by one to three groups which may be the same or different selected from halogen, alkyl and haloalkyl; or represents alkyl or haloalkyl are preferred (compounds in which R1 represents alkyl or haloalkyl are especially preferred) . Compounds of formula (I) above in which R represents alkyl, haloalkyl or cycloalkyl are also preferred (compounds in which R represents i-propyl, sec-butyl, tert-butyl, 2,2- dimethylpropyl, 2 , 2 , 2-trifluoroethyl or cyclopentyl are especially preferred) .
Compounds of formula (I) above in which R2 represents hydrogen, alkyl or haloalkyl are preferred. More preferably P.2 represents hydrogen, methyl or ethyl. Most preferably R2 represents methyl.
Compounds of formula (I) above in which R3 represents CONHR9 or COR10 are preferred (compounds in which R9 represents phenyl optionally substituted by one to three groups which may be the same or different selected from halogen, alkyl, haloalkyl and nitro; or in which R10 represents cycloalkyl containing from three to six carbon atoms or cycloalkenyl containing five or six carbon atoms, the ring systems of which are optionally substituted by a group R19 ; or R10 represents an optionally halogenated alkyl group containing up to four carbon atoms which is substituted by cycloalkyl containing from three to six carbon atoms (the cycloalkyl ring may be optionally substituted by one or more halogen or alkyl groups) ; or R10 represents -CH2- (phenyl substituted by one to three groups selected from halogen, methyl and trifluoromethyl) are especially preferred) . Compounds of formula (I) above in which R3 represents CONHR9 in which R9 represents phenyl optionally substituted by one to four groups which may be the same or different selected from halogen, alkyl, haloalkyl, nitro and alkoxy (most pref rably R9 represents 3-halophenyl , 2 , 5-dihalophenyl, 3 , 5-dihaloρhenyl, 2-halo-5- haloalkylphenyl, 3-haloalkylphenyl or 2-halo-5- alkylphenyl) .
Compounds of formula (I) above in which R^ and R5 represent methyl are particularly preferred.
Compounds of formula (I) above in which Y represents -0- are preferred.
A preferred class of compounds of formula (I) above are those wherein:
X represents -S-, -0- or NR12 in which R12 represents hydrogen or alkyl ; Y represents-O- ;
R1 represents phenyl which is optionally substituted by one to three groups which may be the same or different selected from halogen, alkyl and haloalkyl; or represents alkyl or haloalkyl;
R2 represents hydrogen, alkyl or haloalkyl; R3 represents CONHR9 in which R9 represents phenyl optionally substituted by one to three groups which may be the same or different selected from halogen, alkyl, haloalkyl and nitro; or R3 represents COR10 in which R10 represents cycloalkyl containing from three to six carbon atoms, the ring system of which is optionally substituted by a group R19; or R1 represents an optionally halogenated alkyl group containing up to four carbon atoms which is substituted by cycloalkyl containing from three to six carbon atoms (the cycloalkyl ring is optionally substituted by one or more halogen or alkyl groups); or R10 represents -CH2- (phenyl substituted by one to three groups selected from halogen, methyl and trifluorom thyl) ,- and R^ and R5 represent methyl . A more preferred class of compounds of formula (I) above are those wherein: X represents -S-;
Y represents -0-; R1 represents alkyl or haloalkyl;
R2 represents hydrogen, methyl or ethyl; R3 represents CONHR9 in which R9 represents phenyl substituted by one to three groups which may be the same or different selected from halogen, methyl and trifluoromethyl ; or R3 represents COR10 in which R10 represents cycloalkyl containing from three to six carbon atoms optionally substituted by alkyl; or R10 represents an optionally halogenated alkyl group containing up to four carbon atoms which is substituted by cycloalkyl containing from three to six carbon atoms (the cycloalkyl ring may be optionally substituted by an alkyl group) ; and R^ and R5 represent methyl . A further more preferred class of compounds of formula (I) above are those wherein: X represents -S- ;
Y represents -O- ;
R1 represents C2-C5 alkyl or haloalkyl, cyclopentyl, cyclohexyl, or phenyl optionally substituted by a halogen atom; R2 represents methyl;
R3 represents CONHR9 in which R9 represents phenyl substituted by one to four groups which may be the same or different selected from halogen, methyl, halomethyl, nitro and methoxy; or R3 represents C02Rl in which R11 represents alkyl; or R3 represents phenyl substituted by two halogen atoms ; and R^ and R^ represent methyl .
Particularly preferred compounds of formula (I) are: N- (2, 5-difluorophenyl) -2- (2 , 3-dihydro-6- methyl-4-oxo-5-phenylthio-4H-l, 3-oxazin-3-yl) -2- methylpropanamide (compound 1) ;
N-(3, 5-difluorophenyl) -2- (2 , 3-dihydro-6- methyl-4-oxo-5-phenyithio-4H-l, 3-oxazin~3-yl) -2 - methylpropanamide (compound 2);
N- (2-chloro-5-trifluoromethylphenyl) -2- (2, 3- dihydro-6-methyl-4-oxo-5-phenylthio-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 3); N-(2, 5-difluorophenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3- yl) -2-methylpropanamide (compound 4);
N-(3, 5-difluorophenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 5 ) ;
N- ( 2-chloro-5-trifluoromethylphenyl) -2- (2, 3- dihydro-5-isopropylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 6) ; N-(2, 5-difluorophenyl) -2- [2 , 3-dihydro-5- (3- fluorophenylthio) -6-methyl-4-oxo-4H-l, 3-oxazin- 3 -yl] -2-methylpropanamide (compound 7);
N- (3, 5-difluorophenyl) -2- [2, 3-dihydro-5- (3- fluorophenylthio) -6-methyl-4-oxo-4H-l, 3-oxazin- 3 -yl] -2-methylpropanamide (compound 8 ) ; N- (2-chloro-5-trifluoromethylphenyl) -2- [2,3- dihydro-5- ( 3 -fluorophenylthio) -6-methyl-4-oxo- 4H-1 , 3-oxazin-3-yl] -2-methylpropanamide (compound 9) ;
N- (3 , 5-dichlorophenyl) -2- (2, 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3- yl) -2-methylpropanamide (compound 10);
N-(5-chloro-2-methylphenyl)-2- (2 , 3-dihydro- 5-isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 11); N-(2-fluoro-5-trifluorophenyl) -2-(2,3- dihydro-5-isopropy1thio-6-methyl-4-oxo-4H-1,3- oxazin-3-yl) -2-methylpropanamide (compound 12); N- ( 5-fluoro-2-methylphenyl) -2- (2 , 3-dihydro- 5-isopropylthio-6-methyl-4-σxo-4H-l , 3-oxazin-3- yl ) -2-methylpropanamide (compound 13);
N- ( 3-trifluoromethylphenyl) -2- (2 , 3-dihydro- 5-isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 14);
N- ( 5-chloro-2-fluorophenyl ) -2- (2 , 3-dihydro- 5-isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 15); N-(3-chloro-5-fluorophenyl) -2- (2 , 3-dihydro-
5-i≤opropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 16);
N-(2, 4-difluorophenyl) -2 - (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 17);
N-(3-chlorophenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 18);
N- (3-nitrophenyl) -2 - (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 19); tert-butyl 2- (2 , 3-dihydro-5-isopropylthio-6- methyl-4-oxo-4H-l, 3-oxazin-3-yl) -2- methylpropionate (compound 20); tert-butyl 2- [2 , 3-dihydro-5- (3- fluorophenylthio) -6-methyl-4-oxo-4H-l, 3-oxazin- 3-yl] -2-methylpropionate (compound 21); ethyl 2- (2 , 3-dihydro-5-isopropylthio-6- methyl-4-oxo-4H-l, 3-oxazin-3-yl) -2- methylpropionate (compound 22); tert-butyl 2- (2, 3-dihydro-6-methyl-4-oxo-5- phenylthio-4H-l, 3-oxazin-3-yl) -2- methylpropionate (compound 23);
6-methyl-3- [1-methyl-l- (3,5- dichlorophenyl) ethyl] -5-phenylthio-2 , 3-dihydro- 4H-1, 3-oxazin-4-one (compound 24); 5-isopropylthio-6-methyi-3- [1-methyl-l- (3,5- dichlorophenyl) ethyl] -2 , 3-dihydro-4H-l , 3-oxazin- 4-one (compound 25) ;
3 , 5-dichiorophenyl 2- ( 2 , 3 -dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropionate (compound 26); cyclobutyl 2- (2 , 3-dihydro-5-isopropylthio-6- methyl-4-oxo-4H-l , 3-oxazin-3 -yl) -2- methylpropionate (compound 27); allyl 2- (2 , 3-dihydro-5-isopropylthio-6- methyl-4-oxo-4H-l, 3-oxazin-3 -yl) -2- methylpropionate (compound 28); but-l-en-3-yl 2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropionate (compound 29);
N-(2, 5-difluorophenyl) -2- (2 , 3-dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 138);
N- (3 , 5-difluorophenyl) -2 - (2, 3-dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 139);
N- (2-fluoro-5-trifluoromethylphenyl) -2- (2, 3- dihydro-5-isobutylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 143); N-(2, 5-difluorophenyl) -2- (2 , 3-dihydro-5-sec- butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) -2- methylpropanamide (compound 157);
N- (3 , 5-difluorophenyl) -2- (2 , 3-dihydro-5-sec- butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) -2- methylpropanamide (compound 158) ;
N-(2-fluoro-5-trifluoromethylphenyl) -2-(2,3- dihydro-5-sec-butylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 162); N- (3-trifluoromethylphenyl) -2- (2 , 3-dihydro- 5-sec-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 164); N- ( 5-chloro-2-fluorophenyl) -2- (2 , 3-dihydro- 5-sec-butylt io-6-me hy1-4-oxo-4H-1, 3-oxazin-3- yl) -2-methylpropanamide (compound 165);
N- (2, 4-difluorophenyl) -2- (2, 3-dihydro-5-sec- butylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3-yl) -2- methylpropanamide (compound 167);
N- (3-nitrophenyl) -2- (2 , 3-dihydro-5-sec- butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) -2- methylpropanamide (compound 169); N-(2, 5-difluorophenyl) -2- (2 , 3-dihydro-5- tert-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 176);
N-(3, 5-difluorophenyl) -2- ( 2 , 3-dihydro-5- tert-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 177);
N- (2-fluoro-5-trifluoromethylphenyl) -2- (2, 3- dihydro-5-tert-butylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 181);
N- (5-chloro-2-fluorophenyl) -2- (2 , 3-dihydro- 5-tert-butylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3- yl) -2-methylpropanamide (compound 184);
N-(3, 5-dichlorophenyl) -2- (2 , 3-dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3- yl) -2-methylpropanamide (compound 290); N-( 5-chloro-2-methylphenyl) -2- (2 , 3-dihydro-
5-cyclopentylthio-6-methyl-4-oxo-4H-l , 3-oxazin- 3 -yl) -2-methylpropanamide (compound 291);
N- (2-fluoro-5-trifluoromethylphenyl) -2- (2,3- dihydro-5-cyclopentylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 292);
N- (2-fluoro-5-methylphenyl) -2- (2 , 3-dihydro- 5-cyclopentylthio-6-methyl-4-oxo-4H-l, 3-oxazin- 3 -yl) -2-methylpropanamide (compound 293);
N- (3-trifluoromethylphenyl) -2- (2 , 3-dihydro- 5-cyclopentylthio-6-methyl-4-oxo-4H-l, 3-oxazin- 3 -yl) -2-methylpropanamide (compound 294); N- (5-chloro-2-f luorophenyl) -2- (2 , 3-dihydro- 5-cyclopentylthio-6-methyl-4-oxo-4H~l, 3-oxazin- 3 -yl) -2-methylpropanamide (compound 295);
N-(3-chlorophenyl) -2- (2 , 3-dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 296);
N- (3-nitrophenyl) -2- (2, 3-dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 297) ; N-(2-fluoro-5-nitrophenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 298) ;
N- (5 -chloro-2 -nitrophenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 299) ;
N- (2-f luoro- 5- tr if luoromethylphenyl) -2- [2, 3- dihydro-6-methyl-5- (2 , 2-dimethylpropylthio) -4- oxo-4H-l, 3-oxazin-3-yl) -2-methylpropanamide (compound 300) ; N- (5 -chloro-2- fluorophenyl) -2- [2 , 3-dihydro-
6-methyl-5- (2 , 2-dimethylpropylthio) -4-oxo-4H- 1, 3-oxazin-3-yl) -2-methylpropanamide (compound 301) ;
N-( 3 -nitrophenyl) -2- [2, 3-dihydro-6-methyl-5- (2 , 2-dimethylpropylthio) -4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 302) ;
N- (2, 5-difluorophenyl) -2- [2 , 3-dihydro-5- (2- f luorophenylthio) -6-methyl-4-oxo-4H-l, 3-oxazin- 3 -yl) -2-methylpropanamide (compound 303) ; N-(2-fluoro-5-trifluoromethylphenyl) -2-[2,3- dihydro-5- (2-f luorophenylthio) -6-methyl-4-oxo- 4H-1, 3-oxazin-3-yl) -2-methylpropanamide (compound 304) ;
N- (3-trif luoromethylphenyl) -2- [2, 3-dihydro- 5- (2-f luorophenylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 305); N- ( 5-chloro-2-fluorophenyl) -2- [2, 3-dihydro- 5- (2-fluorophenylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 306); N-(3-nitrophenyl) -2- [2, 3 -dihydro-5- (2- fluorophenylthio) -6-methyl-4-oxo-4H-l, 3-oxazin- 3 -yl) -2-methylpropanamide (compound 307);
N- (2, 4-difluorophenyl) -2- [2, 3 -dihydro-5- (2- fluorophenylthio) -6-methyl-4-oxo-4H-l, 3-oxazin- 3-yl) -2-methylpropanamide (compound 308); N-(3, 5-dichlorophenyl) -2- [2 , 3-dihydro-5- (2- fluorophenylthio) -6-methyl-4-oxo-4H-l, 3-oxazin- 3-yl) -2-methylpropanamide (compound 309);
N- (2-fluoro-5-methylphenyl) -2- [2 , 3-dihydro- 5- (2-fluorophenylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 310); N- (2, 5-difluorophenyl) -2- [2 , 3-dihydro-5- (2,2,2-trifluoroethylthio) -6-methyl-4-oxo-4H- 1, 3-oxazin-3-yl) -2-methylpropanamide (compound 311); N- (2-fluoro-5-trifluoromethylphenyl) -2- [2 , 3- dihydro-5- (2,2 , 2-trifluoroethylthio) -6-methyl-4- oxo-4H-l, 3-oxazin-3-yl] -2-methylpropanamide (compound 312) ;
N- (3-trifluoromethylphenyl) -2- [2 , 3-dihydro- 5- (2,2, 2-trifluoroethylthio) -6-methyl-4-oxo-4H- 1, 3-oxazin-3-yl] -2-methylpropanamide (compound 313);
N- (5-chloro-2-fluorophenyl) -2- [2 , 3-dihydro- 5- (2 , 2, 2-trifluoroethylthio) -6-methyl-4-oxo-4H- 1, 3-oxazin-3-yl] -2-methylpropanamide (compound 314);
N- (3-nitrophenyl) -2- [2 , 3 -dihydro-5- (2 , 2 , 2- trifluoroethylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 315); N- (2-fluoro-5-methylphenyl) -2- (2 , 3-dihydro-
5-sec-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 316);
SUBS TUTESHEET(RULE26) N- (3 , 5-difluorophenyl) -2- (2 , 3-dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 317);
N- (2, 5-difluorophenyl) -2- ( 2 , 3-dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl ) -2-methylpropanamide (compound 318); N- (3-bromophenyl) -2- (2 , 3 -dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 319); N-(3-methoxyphenyl) -2- (2 , 3 -dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 320);
N- (2-fluorophenyl) -2- (2, 3 -dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 321); N-(3-iodophenyl) -2- (2 , 3 -dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 322);
N- ( 4-fluoro-3-trifluoromethylphenyl) -2- (2,3- dihydro-5-cyclopentylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 323);
N-(2, 4, 5-trifluorophenyl) -2- (2 , 3-dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 324); N-(2,3,4, 5-tetrafluorophenyl) -2- (2,3- dihydro-5-cyclopentylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 325);
N- (3-bromophenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 326);
N- (3-methoxyphenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 327); N-( 2-fluorophenyl) -2- (2, 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 328); N-(3-iodophenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3- yl) -2-methylpropanamide (compound 329);
N- (4-fluoro-3-trifluoromethylphenyl) -2- (2,3- dihydro-5-isopropylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 330);
N- (2, 4, 5-trifluorophenyl) -2- (2, 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 331); N- (2, 3-difluorophenyl) -2- (2 , 3 -dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3- yl) -2-methylpropanamide (compound 332);
N- (2, 3 , , 5-tetrafluorophenyl) -2- (2,3- dihydro-5-isopropylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 333);
N- (2-bromo-5-fluorophenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 334);
N- (3 -bromophenyl) -2- [2 , 3 -dihydro-5- (2,2- dimethylpropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 335);
N- (2-fluorophenyl) -2- [2, 3-dihydro-5- (2 , 2- dimethylpropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 336); N-(3-iodophenyl) -2- [2 , 3-dihydro-5- (2,2- dimethylpropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 337);
N- (2-bromo-5-fluorophenyl) -2- [2 , 3-dihydro-5- (2, 2-dimethylpropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 338);
N-(3,4, 5-trifluorophenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 339);
N- (3, 4, 5-trifluorophenyl) -2- [2, 3-dihydro-5- (2, 2-dimethylpropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 340); N- ( 3 -fluoromethylphenyl) -2- (2 , 3 -dihydro-5- cyclopentylthio-6-me hyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 341);
N- ( 3 -fluoromethylphenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3- yl) -2-methylpropanamide (compound 342);
N- (3-fluoromethylphenyl) -2- [2, 3-dihydro-5- (2 , 2-dimethylpropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 343); N- ( 3 , 5-difluorophenyl ) -2- ( 2 , 3 -dihydro-5- cyclohexylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 344);
N-(3, 5-difluorophenyl) -2- [2 , 3-dihydro-5- (2- methylbutylthio) -6-methyl-4-oxo-4H-l, 3-oxazin-3- yl] -2-methylpropanamide (compound 345);
N- (3 , 5-difluorophenyl) -2- [2 , 3-dihydro-5- (2,2, 2-trifluoroethylthio) -6-methyl-4-oxo-4H- 1, 3-oxazin-3-yl] -2-methylpropanamide (compound 346) ; N- ( 3-bromophenyl ) -2- [2, 3 -dihydro-5- (3- chloropropylthio) -6-methyl-4-oxo-4H-l, 3-oxazin- 3-yl] -2-methylpropa_nεimide (compound 347);
N- (2-fluoro-5-trifluoromethylphenyl) -2- [2,3- dihydro-5- (3-chloropropylthio) -6-methyl-4-oxo- 4H-1, 3-oxazin-3-yl] -2-methylpropanamide ( compound 348) ;
N- (5-chloro-2-fluorophenyl) -2- [2 , 3-dihydro- 5- (3-chloropropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 349); N-( 3-fluorom thylphenyl) -2- [2 , 3-dihydro-5-
( 3-chloropropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 350);
N- (3-bromophenyl) -2- (2, 3-dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 351);
N-(3-iodophenyl) -2- (2, 3-dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 352); N- (3 , 5-difluorophenyl) -2- [2 , 3-dihydro-5- (2 , 2-dimethylpropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 353); N- ( 2 -chloro-5- rifluoromethylphenyl) -2- [2, 3- dihydro-5- (2 , 2-dimethylpropylthio) -6-methyl-4- oxo-4H-l, 3-oxazin-3-yl] -2-methylpropanamide ( compound 354) ;
N- (3-fluoromethylphenyl) -2- (2, 3 -dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 355) ;
N-(2-chloro-5-fluorophenyl) -2- (2 , 3-dihydro- 5-isobutylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3- yl) -2-methylpropanamide (compound 356);
N- (5-chloro-2-fluorophenyl) -2- (2 , 3-dihydro- 5-isobutylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 357);
N-( 3 -fluorophenyl) -2- (2 , 3-dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 358) ; N-(2-bromo-5-fluorophenyl) -2- (2 , 3-dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 359) ;
N-(3,4, 5-trifluorophenyl) -2- (2 , 3 -dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 360);
N- (2-fluoro-5-trifluoromethylphenyl) -2- (2, 3- dihydro-5-n-butylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 361); N- (2-chloro-5-fluorophenyl) -2- (2 , 3-dihydro- 5-n-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 362);
N- (5-chloro-2-fluorophenyl) -2- (2, 3-dihydro- 5-n-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 363); N-(3-fluorophenyl) -2- (2, 3 -dihydro-5-n- butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) -2- methylpropanamide (compound 364) ;
SUBS TUTESHEET (RULE26) N- (2 , 4, 5-trifluorophenyl) -2- (2 , 3 -dihydro-5- n-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 365);
N- (2, 5-difluorophenyl) -2- [ 2 , 3-dihydro-5- (2- methylbutylthio) -6-methyl-4-oxo-4H-l , 3 -oxazin-3- yl] -2-methylpropanamide (compound 366);
N-(3, 5-difluorophenyl) -2- [2 , 3-dihydro-5- (2- methylbutylthio) -6-methyl-4-oxo-4H-l , 3 -oxazin-3- yl] -2-methylpropanamide (compound 367); N-(3-bromophenyl)-2-[2,3-dihydro-5-(2- methylbutylthio) -6-methyl-4-oxo-4H-l , 3-oxazin-3- yl] -2-methylpropanamide (compound 368);
N-(3-iodophenyl) -2- [2, 3-dihydro-5- (2- methylbutylthio) -6-methyl-4-oxo-4H-l , 3-oxazin-3- yl] -2-methylpropanamide (compound 369);
N- (2-fluoro-5-trifluoromethylphenyl) -2- [2,3- dihydro-5- ( 2-methylbutylthio ) -6-methyl-4-oxo-4H- 1, 3 -oxazin-3-yl] -2-methylpropanamide (compound 370) ; N- (3-fluoromethylphenyl) -2- [2 , 3-dihydro-5-
(2-methylbutylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 371);
N- (2-chloro-5-fluorophenyl) -2- [2 , 3-dihydro- 5- (2 -methylbutylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 372); N- ( 5-chloro-2-fluorophenyl) -2- [2 , 3-dihydro- 5- (2-methylbutylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 373); N- (3-fluorophenyl) -2- [2 , 3 -dihydro-5- (2- methylbutylthio) -6-methyl-4-oxo-4H-l , 3-oxazin-3- yl] -2-methylpropanamide (compound 374);
N-(2,4, 5-trifluorophenyl) -2- [2 , 3-dihydro-5- (2-methylbutylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 375); N-( 3, 4, 5-trifluorophenyl) -2- [2 , 3-dihydro-5-
(2-methylbutylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 376); N- (3 -bromophenyl) -2- (2 , 3 -dihydro-5-tert- butylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3-yl) -2- methylpropanamide (compound 377);
N- (3-iodophenyl) -2- (2 , 3-dihydro-5-tert- butylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3-yl) -2- methylpropanamide (compound 378);
N- (3-fluoromethylphenyl) -2- (2 , 3-dihydro-5- tert-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 379); N- ( 2 -chloro-5-fluorophenyl) -2- (2 , 3-dihydro-
5-tert-butylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3- yl) -2-methylpropanamide (compound 380);
N-( 3 -fluorophenyl) -2- (2 , 3-dihydro-5-tert- butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) -2- methylpropanamide (compound 381);
N- ( 2-bromo-5- fluorophenyl) -2- (2 , 3-dihydro-5- tert-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 382);
N- (2, 4, 5-trifluorophenyl) -2- (2, 3-dihydro-5- tert-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 383); and
N- (3 , 4, 5-trifluorophenyl) -2- (2 , 3-dihydro-5- tert-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 384) .
The following compounds of formula (la) below and shown in Table 1 also form part of the present invention.
Figure imgf000023_0001
'.la)
In the table below NPh' means phenyl, λ e' means methyl, 'Et' means ethyl, 'Pr' means propyl, xiPr' means isopropyl, vcPr' means cyclopropyl, λBu' means butyl, iBu' means isobutyl, ' sBu' means sec-butyl, tBu' means tert-butyl, lcBu' means cyclobutyl, 'cPe' means cyclopentyl and cHex' means cyclohexyl. Where subscripts are omitted after atoms it will be understood that they are intended, for example C02Et means C02Et.
Table 1
Figure imgf000024_0001
Figure imgf000025_0001
Figure imgf000026_0001
Figure imgf000027_0001
Figure imgf000028_0001
Figure imgf000029_0001
Figure imgf000030_0001
Figure imgf000031_0001
Figure imgf000032_0002
Compounds of formula (I) above may be prepared by the application or adaptation of known methods (i.e. methods heretofore used or described in the literature) . It is to be understood that in the descriptions of the following processes the sequences may be performed in different orders and that suitable protecting groups may be required to achieve the compounds sought.
According to a feature of the present invention compounds of formula (I) wherein R , X, Y, R2 , R4 and R^ are as defined above and R3 is -CONHR9 wherein R9 is as defined above, may be prepared by the reaction of a compound of general formula (II) :
Figure imgf000032_0001
( ii : wherein R1 , X, Y, R , R4 and R5 are as defined above, with an amine of formula (III) :
R9NH2 (III) wherein R9 is as defined above. The reaction is generally performed in the presence of a base, for example a tertiary amine such as triethylamine and in an inert solvent such as dichloromethane at a temperature from 0°C to the reflux temperature of the solvent. According to a further feature of the present invention compounds of formula (I) wherein R1 , X, Y, R2 , R4 and R5 are as defined above and R3 is -CONHR9 wherein P.9 is as defined above, may also be prepared by the reaction of a compound of formula (IV) :
Figure imgf000033_0001
(IV) wherein R1, X, Y, R2 , R4 and R5 are as defined above, with an amine of formula (III) above wherein R9 is as defined above, and a coupling reagent. The coupling reagent is for example N,N' -dicyclohexylcarbodiimide (DCCI) .
The reaction is performed optionally in the presence of a base for example 4- dimethylaminopyridine (DMAP) and in an inert solvent such as dichloromethane at a temperature from 0 to 60°C.
According to a further feature of the present invention compounds of formula (I) wherein R1, X, Y, R , R4 and R5 are as defined above, and R3 represents C0 Rxl and R11 is defined above, may be prepared by the reaction of a compound of formula (II) with an alcohol of formula (V) : RxlOH (V) wherein R 1 is as defined above. The reaction is generally conducted using the conditions employed for the above preparation of compounds of formula (I) wherein R3 is -CONHR9 from compounds of formula (II) and (III) . According to a further feature of the present invention compounds of formula (I) wherein R1, Y, R2 , R4 and R^ are as defined above, R3 is COR1^, and X is an oxygen atom or NR12 wherein R1^ and R12 is as defined above, , may be prepared by the oxidation of the corresponding compound of formula (VI) :
Figure imgf000034_0001
(VI) wherein R1, Y, R2 , R4, R5 and R10 are as defined above and X is an oxygen atom or NR12. The oxidation is generally carried out with a suitable oxidising agent, such as chromic acid or pyridinium chlorochromate, in an inert solvent such as ether or dichloromethane, and at a temperature of from 0°C to the boiling point of the solvent.
According to a further feature of the present invention compounds of formula (I) wherein R1 , X, R2 , R3 , R4 and R5 are as defined above and Y is an oxygen atom may be prepared by the reaction of a compound of formula (VII) :
Figure imgf000034_0002
(VII) wherein P.1, X and R2 are as defined above, with an imir.e of formula (VIII) :
Figure imgf000035_0001
(VIII) wherein R3 , R4 and R^ are as defined above and R is an alkyl group (preferably methyl or ethyl) . The reaction is generally performed in the presence or absence of solvent and at a temperature from 90°C to 200°C or the boiling point of the solvent. The solvent when used is inert, for example xylene, and the acetone produced is preferably removed by distillation.
According to a further feature of the present invention compounds of formula (I) wherein R1 , X, R2 , R3 , R4 and R5 are as defined above and Y is an oxygen atom may also be prepared by the reaction of a compound of formula (IX) :
R2C(0)-CH{XR )-C02R (IX) wherein R1 , X and R2 are as defined above and R represents an alkyl group (preferably methyl or ethyl), with an i ine of formula (VIII) wherein R3 , R4 and R^ are as defined above. The reaction is performed utilising similar conditions to those used for the preparation of compounds of formula (I) wherein Y is an oxygen atom from compounds of formula (VII) above and preferably with removal of the alcohol ROH formed in the reaction. According to a further feature of the present invention compounds of formula (I) wherein R1 , X, R2 , R3 , R4 and R5 are as defined above and Y is -CH2- may be prepared by the reaction of a compound of formula (X) :
Figure imgf000036_0001
(X) wherein R1, X, R2 , R3 , R4 and R5 are as defined above, with a base. The base is generally an alkali metal alkoxide or carbonate such as sodium methoxide or potassium carbonate, in an inert solvent such as ethanol, or with an alkali metal hydride such as sodium hydride, in an inert solvent such as tetrahydrofuran, and at a temperature from 0°C to 100°C.
According to a further feature of the present invention compounds of formula (I) in which m, n, p, t, u or v represent one or two may be prepared by the oxidation of the sulphur atom of the corresponding compounds in which m, n, p, t, u or v represent zero or one. The oxidation of the sulphur atom is generally carried out using for example 3-chloroperbenzoic acid in an inert solvent such as dichloromethane at a temperature from -40°C to room temperature. Compounds of formula (I) above may be prepared by interconversion of other compounds of formula (I) and such conversions constitute further features of the present invention. Examples of such processes are known in the art, for example as described in International Patent Publication Number 97/00865.
Acid chlorides of formula (II) may be prepared by the reaction of the corresponding acids of formula (IV) above with a chlorinating agent, for example oxalyl chloride or a mixture of triphenylphosphine and carbon tetrachloride . The reaction with oxalyl chloride may be performed in an inert solvent for example dichloromethane optionally in the presence of a catalyst, for example N,N-dimethylformamide, at a temperature from 0 to 50°C. The reaction with triphenylphosphine and carbon tetrachloride may be performed in an inert solvent, for example toluene or excess carbon tetrachloride, and at a temperature from 20 to 120°C.
Carboxylic acids of formula (IV) may be prepared by the hydrolysis of an ester of formula (XI) :
Figure imgf000037_0001
(XI) wherein R1, X, Y, R2 , R3 , R4 and R5 are as defined above and R represents an alkyl group, preferably methyl or ethyl (i.e. a compound of formula (I) in which R3 represents C0 R11 and R11 represents alkyl) . The reaction is generally performed in the presence of a base for example sodium or potassium hydroxide and in a solvent, e.g. aqueous alcohol at a temperature from 0°C to the reflux temperature of the solvent. Alternatively when R represents a tert-butyl group the reaction may be performed using an acid such as trifluoroacetic acid in a solvent such as dichloromethane optionally in the presence of water at a temperature from 0°C to 50°C.
Intermediate alcohols of formula (VI) wherein R1, Y, R2 , R4 and R^ are as defined above and X is an oxygen atom or NR1 , may be prepared by the reaction of aldehydes of formula (XII) :
Figure imgf000038_0001
(XII) with an organometallic reagent of formula Rχ0-M, wherein R1^ is as defined above and M is a metallic group, preferably a magnesium bromide group or a lithium atom. The reaction is generally performed in an inert solvent such as ether or tetrahydrofuran and at a temperature of from -78°C to the reflux temperature of the solvent.
Intermediates of formula (XII) wherein R1, Y, R , R4 and R^ are as defined above and X is an oxygen atom or NR1 , may be prepared by the reduction of esters of formula (XI) wherein R is alkyl, preferably ethyl. The reaction is generally performed using a suitable reducing agent such as lithium aluminium hydride, in an inert solvent such as tetrahydrofuran, at a temperature of from -78°C to 20°C Imines of formula (VIII) may be prepared by the reaction of amines of formula (XIII) :
Figure imgf000038_0002
(XIII) wherein R3 , R4 and R^ are as defined above, with formaldehyde, preferably as an aqueous solution and at a temperature from ambient to 60°C.
Intermediates of formula (IX) wherein R1 and R are as defined above, R2 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl, and X is a sulphur atom, may be prepared by the reaction of the corresponding ketoester of formula (XIV) :
R2C(0)-CH(Z)-C02R (XIV) wherein Z is a leaving group such as halogen, preferably chlorine, with a thiol of formula (XV) :
RXSH (XV) The reaction is generally performed in a solvent such as an alcohol, for example iso- propanol, in the presence of a base, for example a tertiary amine such as triethylamine, and at a temperature of from 0°C to 100°C.
Intermediates of formula (IX) wherein R and R are as defined above, R2 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl, and X is an oxygen atom, may be prepared by the reaction of the corresponding ketoester of formula (XIV) wherein Z is a leaving group such as halogen, preferably chlorine, with a compound of formula (XVI) :
Rx0H (XVI) The reaction is generally performed in the presence of boron trifluoride etherate and iodosobenzene, according to the procedure of R.M.Moriarty et.al. described in Tetrahedron, 44(6), 1603-1607 (1988). Solvents such as chloroform, or an alcohol for example iso- propanol are generally used, with a reaction temperature of from 0°C to 50°C. Intermediates of formula (IX) wherein R1 and
R are as defined above, R2 is alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl or haloalkynyl, and X is -NR12 , may be prepared by the reaction of the corresponding ketoester of formula (XIV) with an amine of formula (XVII) :
RXNH(R12) (XVII) The reaction is generally conducted with or without a solvent, optionally in the presence of a base such as a trialkylamine for example triethylamine, at a temperature of from 0°C to 150°C.
Intermediates of formula (X) wherein R1, X, R , R3 , R4 and R^ are as defined above, may be prepared by the reaction of compounds of formula (XVIII) :
Figure imgf000040_0001
(XVIII) wherein R2 , R3 , R4 and R5 are as defined above, with an acid chloride of formula (XIX) :
Figure imgf000040_0002
(XIX) wherein R1 and X are as defined above . The reaction is generally performed using the same conditions as those used to prepare compounds of formula (I) above wherein R9 is -CONHR9 from compounds of formula (II) .
Compounds of formula (II), (IV), (VI), (X) and (XII) are novel and as such constitute a further feature of the present invention.
Compounds of formula (III), (V), (VII), (XIII), (XIV), (XV), (XVI), (XVII), (XVIII) and (XIX) are known or may be prepared by the application or adaptation of known methods. The compounds of formula (I) can be converted into salts which can be prepared by known methods .
The following non-limiting Examples illustrate the invention. 1H-NMR spectra (shifts in ppm) were run in CDCI3 unless otherwise stated. Where MS values appear they refer to the observed molecular ion (m+1 "or m-1 or characterising fragment) in the electrospray mass spectrum for the compound. Example 1
A mixture of 2- (2 , 3-dihydro-6-methyl-4-oxo- 5-phenylthio-4H-l, 3-oxazin-3-yl) -2- methylpropionic acid (lOOmg) in dichloromethane was treated with oxalyl chloride (1 drop) and warmed to 30°C. When gas evolution had ceased 2 , 5-difluoroaniline (43mg) was added at 20°C followed by triethylamine (33 microlitres) and stirred for 2 hours . Dichloromethane and water were added and the organic phase washed (water) , dried (sodium sulphate) , evaporated and purified by chromatography on silica gel to give N-(2,5- difluorophenyl) -2- (2 , 3-dihydro-6-methyl-4-oxo-5- phenylthio-4H-l, 3-oxazin-3-yl) -2- methylpropanamide (compound 1, 40mg) , NMR 1.6(s,6H), 2.3(s,3H), 5.2(s,2H), 6.6(m,lH), 6.9- 7.0(m, 6H) , 8.0(m,2H) .
By proceeding in a similar manner the following compounds were also prepared:
N-(3, 5-difluorophenyl) -2- (2 , 3-dihydro-6- methyl-4-oxo-5-phenylthio-4H-l, 3-oxazin-3-yl) -2- methylpropanamide (compound 2), NMR 1.6(s,6H), 2.3(s,3H), 5.2(s,2H), 6.4(m,lH), 6.9-7.1 (m, 7H) , 8.7(s,lH) ;
N- (2-chloro-5-trifluoromethylphenyl) -2- (2,3- dihydro-6-methyl-4-oxo-5-phenylthio-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 3), NMR 1.7(s,6H) , 2.3(s,3H), 5.3(s,2H), 7.0- 7.2(m,5H), 7.3(d,lH), 7.4(d,lH), 8.4(s,lH), 8.8(S,1H) ; N- (2 , 5-difluorophenyl) -2- (2 , 3 -dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 4), NMR l.l(d,6H), 1.6(s,6H), 2.3(s,3H), 3.2(m,lH), 5.1(s,2H), 6.6(m,lH), 5.9(m,lH), 3.1(m,2H);
N-(3, 5-difluorophenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3- yl) -2-methylpropanamide (compound 5), NMR l.l(d,6H), 1.6(s,6H), 2.3(s,3H), 3.2(m,lH), 5.1(s,2H), 6.4(t,lH), 7.0{d,2H), 8.6(s,lH);
N- (2-chloro-5-trifluoromethylphenyl) -2- (2 , 3- dihydro-5-isopropylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 6), NMR 1.2(d,6H) , 1.7(s,6H), 2.3(s,3H), 3.3(m,lH), 5.2(s,2H), 7.2(d,lH), 7.4(d,lH), 8.5(s,lH), 8.8 (s, 1H) ;
N- (2, 5-difluorophenyl) -2- [2 , 3-dihydro-5- (3- fluorophenylthio) -6-methyl-4-oxo-4H-l, 3-oxazin- 3-yl] -2-methylpropanamide (compound 7), NMR 1.7(s,6H), 2.3(s,3H), 5.4(s,2H), 6.7-6.8 (m, 2H) , 6.9(d,lH), 7.1(m,lH), 7.3(d,lH), 7.4(d,lH), 8.4(s,lH), 8.8(s,lH); N-(3, 5-difluorophenyl) -2- [2, 3-dihydro~5- (3- fluorophenylthio) -6-methyl-4-oxo-4H-l, 3-oxazin- 3-yl] -2-methylpropanamide (compound 8), NMR 1.7(s,6H), 2.3(s,3H), 5.3(s,2H), 6.5(m,lH), 6.8(m,2H), 6.9(d,lH), 7.0-7.2 (m, 3H) , 8.6(s,lH); N- (2-chloro-5 -trifluoromethylphenyl) -2- [2, 3- dihydro-5- (3-fluorophenylthio) -6-methyl-4-oxo- 4H-1, 3-oxazin-3-yl] -2-methylpropanamide (compound 9), NMR 1.7(s,6H), 2.3(s,3H), 5.3(s,2H), 6.7-6.8(m,3H) , 6.9(d,lH), 7.0(m,lH), 7.1(m,lH), 8.1(m,2H);
N-(3, 5 -dichlorophenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 10), NMR 1.2(d,6H), 1.6(s,6H), 2.3(s,3H), 3.3(m,lH), 5.2(s,2H), 7.1(s,lH), 7.5(s,2H), 8.6(s,lH);
N-(5-chloro-2-methylphenyl)-2- (2 , 3-dihydro- 5-isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 11), NMR 1.2(d,6H) , 1.7(s,6H) , 2.2(s,3H) , 2.3(s,3H) , 3.3 (m,lH) , 5.2(s,2H) , 7.0-7.2 ( , 2H) , 8.0(s,lH) , 8.1(s,lH) ;
N- (2-f luoro- 5- rif luorophenyl) -2- (2, 3- dihydro-5-isopropylthio-6-methyl-4-oxo-4H-l , 3- oxazin-3-yl) -2-methylpropanamide (compound 12) , NMR 1.2(d,6K) , 1.7(s,6H) , 2.3 (s,3H) , 3.3(m,lH) , 5.2(S,2H) , 7.1(t,lH) , 7.3 (m,lH) , 8.3(s,lH) , 8.7(d,lH) ; N- (5-fluoro-2-methylphenyl) -2- (2 , 3-dihydro-
5-isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 13) , NMR l.l(d,6H) , 1.6(s,6H) , 2.1(s,3H) , 2.2(s,3H) , 3.2(m,lH) , 5.1(s,2H) , 6.6(t,lH) , 7.0(t,lH) , 7.7(d,lH) , 8.1(s,lH) ;
N- (3-tr if luoromethylphenyl) -2- (2 , 3-dihydro- 5-isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 14) , NMR 1.2(d,6H) , 1.7(s,6H) , 2.3(s,3H) , 3.3(m,lH), 5.2(s,2H) , 7.3(d,lH) , 7.4(t,lH) , 7.7(d,lH),
7.8(Ξ,1H) , 8.6(s,lH) ;
N- (5 -chloro-2 -fluorophenyl) -2- (2, 3-dihydro- 5-isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2 -methylpropanamide (compound 15), NMR l.l(d,6H) , 1.6(s,6H) , 2.3(s,3H) , 3.2(m,lH) ,
5.2(s,2H) , 6.9(m,2H) , 8.1(s,lH) , 8.3(d,lH) ;
N- (3-chloro-5-f luorophenyl) -2- (2 , 3-dihydro- 5-isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 16) , NMR 1.2(d,6H) , 1.6(s,6H) , 2.3(s,3H) , 3.3(m,lH) ,
5.2(s,2H), 6.8(d,lH) , 7.2(s,lH) , 7.3(d,lH) , 8.7 (s, 1H) ;
N- (2, 4-difluorophenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 17), NMR l.l(d,6H), 1.6(s,6H), 2.2(s,3H), 3.2(m,lH), 5.2(s,2H), 6.8(m,2H), 8.0(s,lH), 8.2(m,lH);
SUBSOTUTESHEET(RULE26) N-(3-chlorophenyl) -2- (2, 3-dihydro-5- isopropylthio-6-me hyl-4-oxo-4H-l, 3 -oxazin-3- yl) -2-methylpropanamide (compound 18), NMR 1.2(d,6H), 1.6(s,6H), 2.3(s,3H), 3.3(m,lH), 5.2(s,2H), 7.1(d,lH), 7.2(t,lH), 7.3(d,lH),
7.6(s,lH), 8.5(s,lH);
N-( 3 -nitrophenyl) -2- (2 , 3 -dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3- yl) -2-methylpropanamide (compound 19), NMR 1.2(d,6H), 1.7(s,6H), 2.3(s,3H), 3.3(m,lH), 5.2(s,2H), 6.9-8.7 (m,4H) ;
N-(2, 5-difluorophenyl) -2- (2 , 3-dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 138), MS m+1 399; N-(3, 5-difluorophenyl) -2- (2 , 3-dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 139), MS m+1 399;
N- (2-fluoro-5-trifluoromethylphenyl) -2- (2, 3- dihydro-5-isobutylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 143), MS m+1 449;
N-(2, 5-difluorophenyl) -2- (2 , 3-dihydro-5-sec- butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) -2- methylpropanamide (compound 157), MS m+1 399; N- (3 , 5-difluorophenyl) -2- (2 , 3-dihydro-5-sec- butylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3-yl) -2- methylpropanamide (compound 158), MS m+1 399;
N- (2-fluoro-5-trifluoromethylphenyl) -2- (2,3- dihydro-5-sec-butylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 162), MS m+1 449;
N-(3-trifluoromethylphenyl) -2- (2 , 3-dihydro- 5-sec-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 164), MS m+1 431;
N- ( 5-chloro-2-fluorophenyl ) -2- ( 2 , 3 -dihydro- 5-sec-butylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3-
SUBS TUTESHEET (RULE26) yl) -2-methylpropanamide (compound 165), MS m+1 415;
N-(2, 4-difluorophenyl)-2-(2,3-dihydro-5-sec- butylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 -yl) -2- methylpropanamide (compound 167), MS m+1 399; N- (3 -nitrophenyl) -2- (2 , 3-dihydro-5-sec- butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) -2- methylpropanamide (compound 169), MS m+1 408; N- (2 , 5-difluorophenyl) -2- (2, 3 -dihydro-5- tert-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 176), MS m+1 399;
N- (3 , 5-difluorophenyl) -2- (2 , 3 -dihydro-5- tert-butylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3- yl) -2-methylpropanamide (compound 177), MS m+1 399;
N- ( 2-fluoro-5-trifluoromethylphenyl) -2- (2,3- dihydro-5-tert-butylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 181), MS m+1 449;
N-(5-chloro-2-fluorophenyl) -2- (2, 3-dihydro- 5-tert-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 184), MS m+1 415/417; N-(3, 5-dichlorophenyl) -2- (2 , 3 -dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3- yl) -2-methylpropanamide (compound 290) NMR, 1.4- 1.6(m,4H), 1.6(s,6H), 1.7-1.9 (m, 4H) , 2.3(s,3H), 3.5(m,lH), 5.2(s,2H), 7.1(s,lH), 7.5(d,2H), 8.7 (bs,lH) ;
N- (5-chloro-2-methylphenyl) -2- (2 , 3-dihydro- 5-eyelopenty1thio-6-methy1-4-oxo-4H-1,3-oxazin- 3-yl) -2-methylpropanamide (compound 291), NMR 1.5-1.9(bm,8H) , 1.7(s,6H), 2.2(s,3H), 2.3(s,3H), 3.5(m,lH), 5.2(s,2H), 7.0(m,2H), 7.9(m,lH), 8.1(bs,lH) ;
N- (2-fluoro-5-trifluoromethylphenyl) -2- (2,3- dihydro-5-cyclopentylthio-6-methyl-4-OXO-4H-1, 3- oxazin-3-yi) -2-methylpropanamide (compound 292), NMR 1.4-1.6 (br , 4H) , 1.6(s,6H) , 1.7-1.9 (bm, 4H) , 2.3(s,3H), 3.5(m,lH) , 5.2(s,2H), 7.1(t, 1H) , 7.3(m,iH), 8.3(bs,lH) , 8.7(d,lH) ; N- (2-f luoro-5-meth lphenyl) -2- (2 , 3-dihydro-
5 - cy c lopen ty 1 hio - 6 -me thy 1 - 4 - oxo - 4H- 1 , 3 - oxazin- 3 -yl) -2-methylpropanamide (compound 293), NMR 1.4-1.3(m, 8H) , 1.6(s,6H), 2.2(s,3H), 2.3(s,3H), 3.4(m,lH), 5.1(s,2H) , 6.7(m,lH), 6.8(t, 1H) , 8.0(bs,lH) , 8.1(d,lH) ;
N- (3 -trifluoromethylphenyl) -2- (2 , 3-dihydro- 5-eyelopenty1thio-6-methy1-4-oxo-4H-1 , 3 -oxazin- 3 -yl ) -2-methylpropanamide (compound 294), NMR 1.5(bm,4H), 1.7(s,6H), 1.7-1.9 (bm, 4H) , 2.3(s,3H), 3.5(m,lH), 5.2(s,2H), 7.4(m,2H), 7.7(d,lH), 7.8(s,lH), 8.7(bs,lH);
N- ( 5-chloro-2-fluorophenyl) -2- (2 , 3-dihydro- 5-eyelopenty1thio-6-methyl-4-oxo-4H-1 , 3 -oxazin- 3-yl) -2-methylpropanamide (compound 295), NMR 1.5(bm,4H), 1.6(s,6H), 1.7(bm,4H), 2.3(s,3H), 3.5(m,lH), 5.2(s,2H), 6.9(d,2H), 8.2(bs,lH), 8.4(d,lH) ;
N-(3-chlorophenyl) -2- (2, 3-dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3- yl) -2-methylpropanamide (compound 296), NMR 1.4- 1.6(bm,4H), 1.6(s,6H), 1.6-1.8 (bm, 4H) , 2.3(s,3H), 3.4(m,lH), 5.1(s,2H), 7.0(d,lH), 7.1(t, 1H) , 7.3(d,lH), 7.6(m,lH), 8.5(bs,lH); N-( 3 -nitrophenyl) -2- (2 , 3 -dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 297), NMR 1.4- 1.5(bm,4H), 1.6(s,6H), 1.6-1.8 (bm, 4H) , 2.3(s,3H), 3.4(m,lH), 5.1(s,2H), 7.4(t, 1H) , 7.9(m,2H), 8.3(m,lH), 8.7(bs,lH); N-(2-fluoro-5-nitrophenyl)-2-(2,3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 298), NMR 1.2(d,6H), 1.7(s,6H), 2.3(s,3H), 3.3(m,lH), 5.2(s,2H) , 7.2(t, 1H) , 8.0m,lH) , 8.4(bs,lH) , 9.3(m,lH) ;
N- (5-chloro-2-nitrophenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 299) , NMR l.l(d,6H) , 1.6(s,6H) , 2.3(s,3H) , 3.2(m,lH) , 5.3 (s,2H) , 7.1(d,lH) , 8.1(d,lH) , 9.0(s,lH) , ll.l(bs.lH) ;
N- (2-f luoro-5-trif luoromethylphenyl) -2- [2,3- dihydro-6-methyl-5- (2 , 2-dimethylpropylthio) -4- oxo-4H-l, 3-oxazin-3-yl) -2-methylpropanamide (compound 300) , NMR 0.9(t, 3H) , 1.2(s,6H) , 1.5(q, 2H) , 1.7(s,3H) , 2.3 (s,3H) , 5.2(s,2H) , 7.1(t, 1H) , 7.3(m,lH) , 8.4(bs,lH) , 8.7(m,lH) ; N- (5-chloro-2-f luorophenyl) -2- [2 , 3-dihydro-
6-methyl-5- (2 , 2-dimethylpropylthio) -4-oxo-4H- 1, 3-oxazin-3-yl) -2-methylpropanamide (compound 301) ,NMR 0.9{t, 3H) , 1.2(s,6H) , 1.5(q, 2H) , 1.6(s,6H), 2.3(s,3H) , 5.2(s,2H) , 7.0(d,2H), 8.3(bs,lH) , 8.4(d,lH) ;
N- (3-nitrophenyl) -2- [2, 3-dihydro-6-methyl-5- (2, 2-dimethylpropylthio) -4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 302), NMR 0.9(t, 3H) , 1.2(s,6H), 1.5(σ, 2H) , 1.7(s,6H), 2.3(s,3H), 5.2(s,2H), 7.4(t, 1H) , 7.9(t, 2H) , 8.4(s,lH), 9.1(bs,lH);
N- (2, 5-difluorophenyl) -2- [2 , 3-dihydro-5- (2- fluorophenylthio) -6-methyl-4-oxo-4H-l, 3-oxazin- 3-yl) -2-methylpropanamide (compound 303), NMR 1.7(s,6H), 2.3(s,3H), 5.3(s,2H), 6.7(m,lH), 7.0(m,5H), 8.1(m,2H);
N- (2-fluoro-5-trifluoromethylphenyl) -2- [2,3- dihydro-5- (2-f luorophenylthio) -6-methyl-4-oxo- 4H-1, 3-oxazin-3-yl) -2-methylpropanamide (compound 304) , NMR 1.6 (s , 6H) , 2.3(s,3H) ,
5.2(s,2H) , 6.8(m,2H) , 7.0(m,4H) , 7.2(m,lH) , 8.1(bs,lH) ; N- (3 -trifluoromethylphenyl) -2- [2 , 3-dihydro- 5- (2-fluorophenylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 305), NMR 1.7 (s, 6H) , 2.3(s,3H), 5.3(s,2H), 6.9 (m, 2H) , 7.1(m,2H), 7.4(m,2H), 7.6(d,lH), 7.8(s,lH),
8.6(bs,lH) ;
N- (5-chloro-2-fluorophenyl) -2- [2 , 3-dihydro- 5- (2-fluorophenylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 306), NMR 1.7(s,6H) , 2.3(s,3H), 5.3(s,2H), 6.9(m,4H), 7.1(m,2H), 8.1(bs,lH), 8.4(d,lH);
N- (3 -nitrophenyl) -2- [2 , 3 -dihydro-5- (2- fluorophenylthio) -6-methyl-4-oxo-4H-l, 3-oxazin- 3 -yl) -2-methylpropanamide (compound 307), NMR 1.7(s,6H), 2.3(s,3H), 5.3(s,2H), 6.9(m,2H), 7.1(m,2H), 7.4(t, 1H) , 7.8(d,lH), 7.9(d,lH), 8.3(s,lH), 8.7(bs,lH);
N- (2, 4-difluorophenyl) -2- [2, 3-dihydro-5- (2- fluorophenylthio) -6-methyl-4-oxo-4H-l, 3-oxazin- 3 -yl) -2-methylpropanamide (compound 308), NMR 1.7(s,6H), 2.3(s,3H), 5.3(s,2H), 6.9(m,4H), 7.1(m,2H), 7.9(bs,lH), 8.1(m,lH);
N-(3, 5-dichlorophenyl) -2- [2 , 3-dihydro-5- (2- fluorophenylthio) -6-methyl-4-oxo-4H-l , 3-oxazin- 3 -yl) -2-methylpropanamide (compound 309), NMR
1.7(s,6H), 2.3(s,3H), 5.3(s,2H), 6.9-7.2 (m, 5H) , 7.4(s,2H) , 8.6(bs,lH) ;
N- ( 2-fluoro-5-methylphenyl) -2- [2, 3-dihydro- 5- (2-fluorophenylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 310), NMR 1.7(s,6H) , 2.3(S,3H), 2.3(s,3H), 5.3(s,2H), 7.0(m,4H), 7.0(m,2H), 7.9(bs,lH), 8.1(d,lH);
N-(2, 5-difluorophenyl) -2- [2 , 3-dihydro-5- (2,2 , 2-trifluoroethylthio) -6-methyl-4-oxo-4H- 1, 3 -oxazin-3-yl) -2-methylpropanamide (compound 311) , MS m+1 425;
N- ( 2-fluoro-5-trifluoromethylphenyl) -2-[2,3- dihydro-5- (2,2, 2-trifluoroethy] thio) -6-methyl-4- oxo-4H-l, 3 -oxazin-3 -yl] -2-methylpropanamide (compound 312), MS m+1 475;
N- (3-trifluoromethylphenyl) -2- [2 , 3-dihydro- 5- (2 , 2 , 2-trifluoroethylthio) -6-methyl-4-oxo-4H- 1, 3 -oxazin-3-yl] -2-methylpropanamide (compound 313) , MS m+1 457;
N- (5-chloro-2-fluorophenyl) -2- [2 , 3-dihydro- 5- (2 , 2 , 2-trifluoroethylthio) -6-methyl-4-oxo-4H- 1, 3-όxazin-3-yl] -2-methylpropanamide (compound 314) , MS m+1 441;
N-( 3 -nitrophenyl) -2- [2 , 3 -dihydro-5- (2,2,2- trifluoroethylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 315), MS m+1 434; N- (2-fluoro-5-methylphenyl) -2- (2 , 3-dihydro-
5-sec-butylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 - yl) -2-methylpropanamide (compound 316), MS m+1 447;
N- (3 , 5-difluorophenyl) -2- (2, 3 -dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3- yl) -2-methylpropanamide (compound 317), MS m+1 411;
N-(2, 5-difluorophenyl) -2- (2 , 3-dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l , 3 -oxazin-3 - yl) -2-methylpropanamide (compound 318), MS m+1 455;
N- ( 3 -bromophenyl ) -2- ( 2 , 3 -dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3- yl) -2-methylpropanamide (compound 319), MS m+1 405;
N- (3-methoxyphenyl) -2- (2 , 3-dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 - yl) -2-methylpropanamide (compound 320), MS m+1 393; N-( 2-fluorophenyl) -2- (2 , 3 -dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 321), MS m+1 501; N- (3-iodophenyl) -2- (2 , 3 -dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3- yl) -2-methylpropanamide (compound 322), MS m+1 461; N- (4-fluoro-3-trifluoromethylphenyl) -2- (2, 3- dihydro-5-eye1openty1thio-6-methy1-4-oxo-4H-1,3- oxazin-3-yl) -2-methylpropanamide (compound 323), MS m+1 461;
N-(2,4, 5-trifluorophenyl) -2- (2 , 3 -dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 324), MS m+1 429;
N- (2,3, 4, 5 -tetrafluorophenyl) -2- (2,3- dihydro-5-cyclopentylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3 -yl) -2-methylpropanamide (compound 325), MS M+1 447 ;
N- (3-bromophenyl) -2- (2, 3 -dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 326), MS m+1 429;
N- (3-methoxyphenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3- yl) -2-methylpropanamide (compound 327), MS m+1 379; N-( 2-fluorophenyl) -2- (2, 3 -dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 - yl) -2-methylpropanamide (compound 328), MS m+1 367;
N-(3-iodophenyl) -2- (2 , 3 -dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 - yl) -2-methylpropanamide (compound 329), MS m+1 475;
N- (4-fluoro-3-trifluoromethylphenyl) -2- (2, 3- dihydro-5-isopropylthio-6-methyl-4-oxo-4H-l , 3- oxazin-3-yl) -2-methylpropanamide (compound 330), MS m+1 435;
N- (2, 4, 5-trifluorophenyl) -2- (2, 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 331), MS m+1 403;
N- (2, 3 -difluorophenyl) -2- (2, 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin~3- yl) -2-methylpropanamide (compound 332), MS m+1 385;
N-(2,3, , 5-tetrafluorophenyl) -2- (2,3- dihydro-5-isopropylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 333), MS m+1 421;
N- ( 2-bromo-5-fluorophenyl) -2- (2 , 3 -dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 - yl) -2-methylpropanamide (compound 334), MS m+1 447; N- (3 -bromophenyl) -2- [2, 3 -dihydro-5- (2 , 2- dimethylpropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 335), MS m+1 455;
N-( 2-fluorophenyl) -2- [2 , 3 -dihydro-5- (2 , 2- dimethylpropylthio) -6-methyl-4~oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 336), MS m+1 395;
N- (3-iodophenyl) -2- [2, 3-dihydro-5- (2,2- dimethylpropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 337), MS m+1 503;
N- (2-bromo-5-fluorophenyl) -2- [2 , 3-dihydro-5- (2 , 2-dimethylpropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 338), MS m+1 475;
N-(3,4, 5-trifluorophenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3- yl) -2-methylpropanamide (compound 339), MS m+1 403; N- (3 , 4, 5-trifluorophenyl) -2- [2, 3-dihydro-5-
(2 , 2-dimethylpropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 340), MS m+1 431; N- (3-fluoromethylphenyl) -2- (2 , 3-dihydro-5- cyclopentylthio-6-methyl-4-oxo-4H-l , 3-oxazin-3- yl) -2-methylpropanamide (compound 341), NMR 1.4- 1.6(bm,4H), 1.7-1.9 (bm, 4H) , 1.7(s,6H), 2.3(s,3H), 2.5(m,lH), 5.2(s,2H), 5.3 /5.4 (d, 2H) , 7.1(d,lH), 7.3(t, 1H) , 7.5(d,lH), 7.6(s,12H), 8.5(bs,lH) ;
N- (3-fluoromethylphenyl) -2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3- yl) -2-methylpropanamide (compound 342), NMR 1.2(d,6H), 1.7(s,6H), 2.3(s,3H), 3.3(m,lH), 5.2(s,2H), 5.3/5.4(d,2H) , 7.1(d,lH), 7.3(t, 1H) , 7.5(d,lH), 7.6(s,lH), 8.4(bs,lH);
N- (3-fluoromethylphenyl) -2- [2 , 3-dihydro-5- (2, 2-dimethylpropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 343), MS M+1 409;
N-(3, 5-difluorophenyl) -2- (2 , 3-dihydro-5- cyclohexylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 - yl) -2-methylpropanamide (compound 344), MS m+1 425;
N- (3 , 5-difluorophenyl) -2- [2 , 3-dihydro-5- (2- methylbutylthio) -6-methyl-4-oxo-4H-l, 3-oxazin-3- yl] -2-methylpropanamide (compound 345), MS m+1 413 ;
N- (3 , 5-difluorophenyl) -2- [2 , 3-dihydro-5- (2,2, 2-trifluoroethylthio) -6-methyl-4-oxo-4H- 1, 3-oxazin-3-yl] -2-methylpropanamide (compound 346) , MS m+1 425; N- (3 -bromophenyl) -2- [2 , 3-dihydro-5- (3- chloropropylthio) -6-methyl-4-oxo-4H-l , 3-oxazin- 3 -yl] -2-methylpropanamide (compound 347), MS m-1 459/461/463;
N- (2-fluoro-5-trifluoromethylphenyl) -2- [2, 3- dihydro-5- (3-chloropropylthio) -6-methyl-4-oxo- 4H-1, 3-oxazin-3-yl] -2-methylpropanamide (compound 348), MS m+1 469/471; N- (5-chloro-2-fluorophenyl) -2- [2 , 3-dihydro- 5- (3-chloropropylthio j -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 349), MS m-1 433/435/437; N- (3-fluoromethylphenyl) -2- [2 , 3-dihydro-5-
( 3-chloropropylthio) - 6-methyl-4-oxo-4H-l , 3- oxazin-3-yl] -2-methylpropanamide (compound 350), NMR 1.6(s, 6H) , 1.9(m,2H), 2.3(s,3H), 2.7(t, 2H) , 3.5(t, 2H) , 5.2(s,2H), 5.4/5.2 (d, 2H) , 7.0(d,lH), 7.2(t, 1H) , 7.4(d,lH), 7.5(s,lH), 8.2(bs,lH); N- ( 3 -bromophenyl ) -2- (2 , 3 -dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 351), MS m+1 443; N-(3-iodophenyl) -2- (2 , 3 -dihydro-5- isobutylthio-6-methyl-4-oxo-4Hτl, 3 -oxazin-3 -yl) - 2-methylpropanamide (compound 352), MS m+1 489;
N- (3 , 5-difluorophenyl) -2- [2 , 3-dihydro-5- (2, 2-dimethylpropylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 353), MS m+1 413;
N- (2-chloro-5-trifluoromethylphenyl) -2- [2,3- dihydro-5- (2, 2-dimethylpropylthio) -6-methyl-4- oxo-4H-l, 3-oxazin-3-yl] -2-methylpropanamide (compound 354), MS m+1 479/481; N-( 3-fluoromethylphenyl) -2- (2 , 3 -dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 355), MS m+1 395; N- (2-chloro-5-fluorophenyl) -2- (2 , 3-dihydro- 5-isobutylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 - yl) -2-methylpropanamide (compound 356), MS m+1 415/417;
N- (5-chloro-2-fluorophenyl) -2- (2 , 3-dihydro- 5-isobutylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3- yl) -2-methylpropanamide (compound 357), MS m+1 415/417;
N-( 3 -fluorophenyl) -2- (2 , 3-dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 -yl) - 2-methylpropanamide (compound 358), MS m+1 381; N- (2-bromo-5-fluorophenyl) -2- (2 , 3 -dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 359), MS m+1 461;
N- (3 , 4, 5-trifluorophenyl) -2- (2 , 3-dihydro-5- isobutylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 -yl) - 2-methylpropanamide (compound 360), MS m+1 417;
N- (2-fluoro-5-trifluoromethylphenyl) -2- (2 , 3- dihydro-5-n-butylthio-6-methyl-4-oxo-4H-l, 3- oxazin-3-yl) -2-methylpropanamide (compound 361), MS m+1 449;
N- (2-chloro-5-fluorophenyl) -2- (2 , 3-dihydro- 5-n-butylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 - yl) -2-methylpropanamide (compound 362) MS m+1 415/417; N- (5-chloro-2-fluorophenyl) -2- (2, 3-dihydro-
5-n-butylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 - yl) -2-methylpropanamide (compound 363), MS m+1 415/417;
N- (3 -fluorophenyl ) -2- (2 , 3 -dihydro-5-n- butylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 -yl ) -2- methylpropanamide (compound 364), MS m+1 381;
N-(2,4, 5-trifluorophenyl) -2- (2 , 3-dihydro-5- n-butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) - 2-methylpropanamide (compound 365), MS m+1 417; N-(2, 5-difluorophenyl) -2- [2 , 3 -dihydro-5- ( 2- methylbutylthio) -6-methyl-4-oxo-4H-l, 3 -oxazin-3 - yl] -2-methylpropanamide (compound 366), MS m+1 413;
N-(3, 5-difluorophenyl) -2- [2 , 3 -dihydro-5- (2- methylbutylthio) -6-methyl-4-oxo-4H-l, 3 -oxazin-3 - yl] -2-methylpropanamide (compound 367), MS m+1 413;
N- ( 3 -bromophenyl ) -2- [2, 3 -dihydro-5- ( 2- methylbutylthio) -6-methyl-4-oxo-4H-l, 3 -oxazin-3 - yl] -2-methylpropanamide (compound 368), MS m+1 457;
N- ( 3 -iodopheny1 ) -2- [2 , 3 -dihydro-5- ( 2- methylbutylthio) -6-methyl-4-oxo-4H-l, 3-oxazin-3- yl] -2-methylpropanamide (compound 369), MS m+i 503;
N- (2-fluoro-5-trifluoromethylphenyl) -2- [2,3- dihydro-5- (2-methylbutylthiG ; -6-methyl-4-oxo-4H- 1 , 3-oxazin-3-yl] -2-methylpropanamide (compound 370) , MS m+1 463;
N- (3-fluoromethylphenyl) -2- [2 , 3 -dihydro-5- (2-methylbutylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 371), MS m+1 409;
N- (2-chloro-5-fluorophenyl) -2- [2 , 3-dihydro- 5- (2-methylbutylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 372), MS m+1 429/431; N-(5-chloro-2-fluorophenyl) -2 - [2 , 3-dihydro-
5-(2-methylbutylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 373), MS m+1 429/431;
N-( 3-fluorophenyl) -2- [2, 3 -dihydro-5- (2- methylbutylthio) -6-methyl-4-oxo-4H-l, 3-oxazin-3- yl] -2-methylpropanamide (compound 374), MS m+1 395;
N-(2,4, 5-trifluorophenyl) -2- [2 , 3-dihydro-5- (2-methylbutylthio) -6-methyi-4-oxo-4H-l, 3- oxazin-3 -yl] -2-methylpropanamide (compound 375), MS m+1 431;
N-(3, 4, 5-trifluorophenyl) -2- [2 , 3 -dihydro-5- (2-methylbutylthio) -6-methyl-4-oxo-4H-l, 3- oxazin-3-yl] -2-methylpropanamide (compound 376), MS m+1 431;
N- (3 -bromophenyl) -2- (2, 3 -dihydro-5-tert- butylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 -yl) -2- methylpropanamide (compound 377), MS m+1 443; N-(3-iodophenyl) -2- (2 , 3 -dihydro-5-tert- butylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 -yl) -2- methylpropanamide (compound 378), MS m+1 489;
N- (3-fluoromethylphenyl) -2- (2, 3 -dihydro-5- tert-butylthio-6-methy1-4-OXO-4H-1, 3 -oxazin-3 - yl) -2-methylpropanamide (compound 379), MS m+1 395;
N- (2 -chloro-5-fluorophenyl) -2- (2 , 3-dihydro- 5-tert-butylthio-6-methy1-4-oxo-4H-1, 3 -oxazin-3 - yl) -2-methylpropanamide (compound 380), MS m+1 415/417;
N- (3-fluorophenyl) -2 - ( 2 , 3-dihydro-5-tert- butylthio-6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) -2- methylpropana ide (compound 381) , MS m+1 381; N- (2-bromo-5-fluorophenyl ) -2- (2 , 3-dihydro-5- tert-butylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3- yl) -2-methylpropanamide (compound 382), MS m+1 461;
N- (2 , 4, 5-trifluorophenyl) -2- (2 , 3 -dihydro-5- tert-butylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 - yl) -2-methylpropanamide (compound 383), MS m+1 417; and
N- (3, 4, 5-trifluorophenyl) -2- (2 , 3-dihydro-5- tert-butylthio-6-methyl-4-oxo-4H-l , 3 -oxazin-3- yl) -2-methylpropanamide (compound 384), MS m+1 417.
Example 2
A mixture of ethyl 2- isopropylthioacetoacetate (5.0g) and tert-butyl 2- (N-methyleneamino) -2-methylpropanoate (7.0g) was heated at reflux in xylene with distillation of solvent during 2 hours, adding fresh xylene to maintain a constant volume. After evaporation the residue was triturated (isohexane) to give tert-butyl 2- (2, 3 -dihydro-5-isopropylthio-6- methyl-4-oxo-4H-l, 3 -oxazin-3 -yl) -2 - methylpropionate (compound 20, 2.48g), NMR 1.2(d,6H), 1.4(s,9H), 1.5(s,6H), 2.3(s,3H), 3.3 (m,lH) , 5.1(s,2H) . By proceeding in a similar manner the following compounds were also prepared: tert-butyl 2- [2 , 3-dihydro-5- (3- fluorophenylthio) -6-methyl-4-oxo-4H-l , 3-oxazin- 3 -yl] -2-methylpropionate (compound 21), NMR 1.3(s,9H), 1.4(s,6H), 2.2(s,3H), 5.2(s,2H), 6.7(t,lH), 6.8(d,lH), 6.9(d,lH), 7.1(m,lH); ethyl 2- (2 , 3 -dihydro-5-isopropylthio-6- methyl-4 -oxo-4H-1, 3 -oxazin-3 -yl) -2- methylpropionate (compound 22); and tert-butyl 2- (2 , 3-dihydro-6-methyl-4-oxo-5- phenylthio-4H-l , 3-oxazin-3-yl ) -2- methylpropionate (compound 23). By proceeding in a similar manner but using
N-methylene I-methyl-1- (3 , 5- dichlorophenyl) ethylamine, there was prepared:
6-methyl-3- [1-methyl-l- (3,5- dichlorophenyl ) ethyl ] -5-phenylthio-2 , 3 -dihydro- 4H-1, 3-oxazin-4-one (compound 24); and
5-isopropylthio-6-methyl-3- [1-methyl-l- (3,5- dichlorophenyl) ethyl] -2 , 3-dihydro-4H-l, 3-oxazin- 4-one (compound 25), NMR 1.16(d,6H), 1.7(s,6H), 2.3(s,3H), 3.26(m,lH), 5.18(s,2H), 7.18(m,3H). Example 3
A mixture of 2- ( 2 , 3 -dihydro-5-isopropylthio- 6-methyl-4-oxo-4H-l, 3-oxazin-3-yl) -2- methylpropionic acid (60mg), oxalyl chloride (18 microlitres) and dichloromethane was treated with a drop of N, N-dimethylfor amide and warmed to 30°C for 5 minutes. When gas evolution had ceased 3 , 5-dichlorophenol (36mg) in dichloromethane was added followed by triethylamine (31 microlitres) . The mixture was stirred overnight and chromatographed on silica gel to give 3 , 5-dichlorophenyl 2- (2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l , 3 -oxazin-3- yl) -2-methylpropionate (compound 26, 61mg) , NMR l.l(d,6H), i.6(s,6H), 2.2(s,3H), 3.3(m,lH), 5.2(s,2H), 7.0(s,2H), 7.1(s,lH).
By proceeding in a similar manner the following compounds were also prepared: cyclobutyl 2- (2 , 3 -dihydrc-5-isopropylthio-6- methyl-4-oxo-4H-l, 3 -oxazin-3 -yl) -2- methylpropionate (compound 2 " ) , NMR l.l(d,6H), 1.4(s,6H), 1.4-1.7(m,4H) , 1.9-2.0 (m, 2H) , 2.2(s,3H), 2.2-2.3 (m,2H) , 3.2(m,lH), 4.9(m,lH),
5.2(s,2H) ; allyl 2- (2 , 3-dihydro-5-isopropylthio-6- methyl-4-oxo-4H-l, 3 -oxazin-3 -yl) -2- methylpropionate (compound 22), NMR l.l(d,6H), 1.5(s,6H), 2.2(s,3H), 3.2(m,lH), 4.5(d,2H), 5.1(s,2H), 5.1-5.2(m,2H) , 5.8(m,lH); and but-l-en-3-yl 2- ( 2 , 3-dihydro-5- isopropylthio-6-methyl-4-oxo-4H-l, 3 -oxazin-3 - yl) -2-methylpropionate (compound 29), NMR l.l(d,6H), 1.2(d,3H), 1.5(s,6H), 2.2(s,3H),
3.2(m,lH), 5.0-5.2(m,2H) , 5.1(s,2H), 5.3(m,lH), 5.7-5.8(m,lH) .
Reference Example 1
A mixture of tert-butyl 2- (2 , 3-dihydro-6- methyl-4-oxo-5-phenylthio-4H-l, 3-oxazin-3-yl) -2- methylpropionate (0.72g), trifluoroacetic acid, water and dichloromethane was heated at reflux for six hours. The organic phase was washed (water) , dried (magnesium sulphate) and evaporated to give 2- (2 , 3-dihydro-6-methyl-4- oxo-5-phenylthio-4H-l, 3 -oxazin-3 -yl) -2 - methylpropionic acid (0.52g).
By proceeding in a similar manner the following compound was also prepared: 2- (2 , 3-dihydro-5-isopropylthio-6-methyl-4- oxo-4H-l , 3-oxazin-3-yl ) -2-methylpropionic acid. Reference Example 2
A solution of 3-fluorothiophenol (5.0g) in isopropanol was added slowly to a solution of methyl 2-chloroacetoacetate (3.76ml) and triethylamine (5.16ml) in isopropanol, and the mixture heated at 60°C for 3 hours then left at 20°C for 2 days. The solvent was evaporated, ether and water added and the organic phase dried (magnesium sulphate) and evaporated to give methyl 2- (3-fluorophenylthio ) acetoacetate (7.9g) . By proceeding in a similar manner the following compounds were also prepared: ethyl 2- ( isopropylthio) acetoacetate; and methyl 2- (phenylthio) acetoacetate .
According to a further feature of the present invention, there are provided compositions suitable for herbicidal use comprising one or more of the cyclic amide derivatives of formula I or an agriculturally acceptable salt thereof, in association with, and preferably homogeneously dispersed in, one or more compatible agriculturally- acceptable diluents or carriers and/or surface active agents [i.e. diluents or carriers and/or surface active agents of the type generally accepted in the art as being suitable for use in herbicidal compositions and which are compatible with compounds of formula I] . The term "homogeneously dispersed" is used to include compositions in which the compounds of formula I are dissolved in other components. The term "herbicidal compositions" is used in a broad sense to include not only compositions which are ready for use as herbicides but also concentrates which must be diluted before use. Preferably, the compositions contain from 0.05 to 90% by weight of one or more compounds of formula I.
The herbicidal compositions may contain both a diluent or carrier and surface-active (e.g. wetting, dispersing, or emulsifying) agent.
Surface-active agents which may be present in herbicidal compositions of the present invention may be of the ionic or non-ionic types, for example sulphoricinoleates, quaternary ammonium derivatives, products based "on condensates of ethylene oxide with alkyl and polyaryl phenols, e.g. nonyl- or octyl-phenols, or carboxylic acid esters of anhydrosorbitols which have been rendered soluble by etherification of the free hydroxy groups by condensation with ethylene oxide, alkali and alkaline earth metal salts of sulphuric acid esters and sulphonic acids such as dinonyl- and dioctyl-sodium sulphonosuccinates and alkali and alkaline earth metal salts of high molecular weight sulphonic acid derivatives such as sodium and calcium lignosulphonates and sodium and calcium alkylbenzene sulphonates .
Suitably, the herbicidal compositions according to the present invention may comprise up to 10% by weight, e.g. from 0.05% to 10% by weight, of surface-active agent but, if desired, herbicidal compositions according to the present invention may comprise higher proportions of surface-active agent, for example up to 15% by weight in liquid emulsifiable suspension concentrates and up to 25% by weight in liquid water soluble concentrates .
Examples of suitable solid diluents or carriers are aluminium silicate, microfine silicon dioxide, talc, chalk, calcined magnesia, kieselguhr, tricalcium phosphate, powdered cork, adsorbent carbon black and clays such as kaolin and bentonite. The solid compositions (which may take the form of dusts, granules or wettable powders) are preferably prepared by grinding the compounds of formula I with solid diluents or by impregnating the solid diluents or carriers with solutions of the compounds of formula I in volatile solvents, evaporating the solvents and, if necessary, grinding the products so as to obtain powders . Granular formulations may be prepared by absorbing the compounds of formula I (dissolved in suitable solvents, which may, if desired, be volatile) onto the solid diluents or carriers in granular form and, if desired, evaporating the solvents, or by granulating compositions in powder form obtained as described above. Solid herbicidal compositions, particularly wettable powders and granules, may contain wetting or dispersing agents (for example of the types described above) , which may also, when solid, serve as diluents or carriers. Liquid compositions according to the invention may take the form of aqueous, organic or aqueous-organic solutions, suspensions and emulsions which may incorporate a surface-active agent. Suitable liquid diluents for incorporation in the liquid compositions include water, glycols, glycol ethers, tetrahydrofurfuryl alcohol, acetophenone, cyclohexanone, isophorone, N-alkyl pyrrolidones, toluene, xylene, mineral, animal and vegetable oils, esterified vegetable oils and light aromatic and naphthenic fractions of petroleum (and mixtures of these diluents). Surface-active agents, which may be present in the liquid compositions, may be ionic or non-ionic (for example of the types described above) and may, when liquid, also serve as diluents or carriers. Powders, dispersible granules and liquid compositions in the form of concentrates may be diluted with water or other suitable diluents, for example mineral or vegetable oils, particularly in the case of liquid concentrates in which the diluent or carrier is an oil, to give compositions ready for use.
When desired, liquid compositions of the compound of formula I may be used in the form of self-emulsifying concentrates containing the active substances dissolved in the emulsifying agents or in solvents containing emulsifying agents compatible with the active substances, the simple addition of such concentrates to water producing compositions ready for use.
Liquid concentrates in which the diluent or carrier is an oil may be used without further dilution using the electrostatic spray technique.
Herbicidal compositions according to the present invention may also contain, if desired, conventional adjuvants such as adhesives, protective colloids, thickeners, penetrating agents, spreading agents, stabilisers, sequestering agents, anti-caking agents, colouring agents and corrosion inhibitors. These adjuvants may also serve as carriers or diluents . Herbicidal compositions according to the present invention may also comprise the compounds of formula I in association with, and preferably homogeneously dispersed in, one or more other pesticidally active compounds and, if desired, one or more compatible pesticidally acceptable diluents or carriers, surface-active agents and conventional adjuvants as hereinbefore described.
Examples of other pesticidally active compounds which may be included in, or used in conjunction with, the herbicidal compositions of the present invention include herbicides, for example to increase the range of weed species controlled for example alachlor [2-chloro-2 , 6 ' - diethyl-N- (methoxy-methyl) -acetanilide] , atrazine [2-chloro-4-ethylamino-6- isopropylamino-1, 3 , 5-triazine] , bromoxynil [3,5- dibromo-4-hydroxybenzonitrile] , chlortoluron [N' - (3-chloro-4-methylphenyl ) -N, N-dimethylurea] , cyanazine [2-chloro-4- ( 1-cyano-l- methylethylamino) -6-ethylamino-l, 3 , 5-triazine] , 2,4-D [2 , 4-dichlorophenoxy-acetic acid], dicamba [3 , 6-dichloro-2-methoxybenzcic acid], difenzoquat [1,2- dimethyl-3 , 5-diphenyl- pyrazolium salts] , flampropmethyl [methyl N-2- (N- benzoyl-3-chloro-4-fluoroanilino) - propionate] , fluometuron [N' - (3-trifluoro- methylphenyl) -N, N-dimethylurea] , isoproturon [N ' - ( 4-isopropylphenyl ) -N, N-dimethylurea] , diclofop { (RS)-2-[4-(2,4- dichlorophenoxy) phenoxy] propionic acid) , fenoxaprop and fenoxaprop-P { 2- [4- ( 6-chloro- 1, 3 -benzoxazol-2-yloxy) phenoxy] propionic acid), diflufenican.N- (2 , 4-difluorophenyl) -2- [3- ( trifluoromethyl) phenoxy] -
3-pyridinecarboxamide} , tralkoxydim (2-[l- (ethoxyimino)propyl] -3 -hydroxy-5- mesitylcyclohex-2-enone} , clodinafop {2- [4- (5- chloro-3-fluoro-2-pyridyloxy) henoxy] propionic acid}, sulcotrione [2- (2-chloro-4- methylsulphonylbenzoyl) cyclohexane-1, 3-dione] , flurtamone { 5-methylamino-2-phenyl-4- [3- (trifluoromethyl lphenyl] -3 (2H) -furanone) , aclonifen (2-chloro-6-nitro-3-phenoxyaniline) , and sulfonyiureas (e.g. nicosulfuron) ; insecticides, e.g. synthetic pyrethroids, e.g. permethrin and cypermethrin, and fungicides, e.g. carbamates, e.g. methyl
N- (1-butyl-carbamoyl- benzimidazol-2- yl) carbamate, and triazoles e.g. l-(4-chloro- phenoxy) -3,3- dimethyl-1- (1,2, 4-triazol-l-yl) - butan-2-one. Pesticidally active compounds and other biologically active materials which may be included in, or used in conjunction with, the herbicidal compositions of the present invention, for example those hereinbefore mentioned, and which are acids, may, if desired, be utilized in the form of conventional derivatives, for example alkali metal and amine salts and esters.
The following Examples illustrate herbicidal compositions according to the present invention. The following trade marks appear in the description: Ethylan, Soprophor, Sopropon, Rhodorsil, Atagel, Synperonic, Solvesso, Arkopon, Tixosil, Arylan. Example Cl;
A suspension concentrate is formed from: Compound of formula (I) 20% Ethylan BCP (surfactant) 0.5%
Soprophor FL 0.5%
Sopropon T36 (Dispersant) 0.2%
Rhodorsil 426R (Antifoaming agent) 0.01% Propylene glycol (antifreeze) 5.0% Atagel 50 (anti-settling agent) 2.0
Water to 100%
Similar suspension concentrates may be prepared by replacing Compound 1 with other cyclic amide derivatives of formula I .
Example C2
An emulsion concentrate is formed from the following: Compound of formula 1 10%
Synperonic NPE1800 (surfactant) 4.9% Arylan CA (surfactant) 5.0%
Cyclohexanone (solvent) 9.8%
NMP (solvent) 9.8% Solvesso 150 (blending agent) 5.0%
Water to 100%
Note: NMP means N-methylpyrrolidone Similar emulsion concentrates may be prepared by replacing Compound 1 with other cyclic amide derivatives of formula I.
Example C3
A wettable powder is formed from the following :
Compound of formula 1 20.0%
Arylan SX flake (surfactant) 3.0% Arkopon T (surfactant) 5.0%
Sodium polycarboxylate (dispersant) 1.0% Tixosil 38 (flow aid) 3.0%
China Clay 68.0%
Similar wettable powders may be prepared by replacing Compound 1 with other cyclic amide derivatives of formula I.
According to a feature of the present invention, there is provided a method for controlling the growth of weeds (i.e. undesired vegetation) at a locus which comprises applying to the locus a herbicidally effective amount of at least one cyclic amide derivative of formula I or an agriculturally acceptable salt thereof. For this purpose, the cyclic amide derivatives are normally used in the form of herbicidal compositions (i.e. in association with compatible diluents or carriers and/or surface active agents suitable for use in herbicidal compositions), for example as hereinbefore described.
The compounds of formula I show herbicidal activity against dicotyledonous (i.e. broad- leafed) and monocotyledonous (e.g. grass) weeds by pre- and/or post-emergence application.
By the term "pre-emergence application" is meant application to the soil in which the weed seeds or seedlings are present before emergence of the weeds above the surface of the soil. By the term "post-emergence application" is meant application to the aerial or exposed portions of the weeds which have emerged above the surface of the soil. For example, the compounds of formula I may be used to control the growth of: broad-leafed weeds, for example, Abutilon theophrasti, Amaranthus retroflexus, Bidens pilosa, Chenopodium album, Galium aparine, Ipomoea spp . e.g. Ipomoea purpurea, Lindernia procumbens , Monochoria vaginalis, Sesbania exaltata, Sinapis arvensis, Solanum nigrum and Xanthium strumarium, and grass weeds, for example Alopecurus myosuroides , Avena fatua, Digitaria sanguinalis, Echinochloa crus-galli, Echinochloa oryzicola, Eleusine indica and Setaria sp , e.g. Setaria faberii or Setaria viridis, and sedges, for example, Cyperus esculentus and Scirpus juncoides.
The amounts of compounds of formula I applied vary with the nature of the weeds, the compositions used, the time of application, the climatic and edaphic conditions and (when used to control the growth of weeds in crop-growing areas) the nature of the crops. When applied to a crop-growing area, the rate of application should be sufficient to control the growth of weeds without causing substantial permanent damage to the crop . In general , taking these factors into account, application rates between 1 g and 1000 g of active material per hectare give good results. However, it is to be understood that higher or lower application rates may be used, depending upon the particular problem of weed control encountered.
The compounds of formula I may be used to control selectively the growth of weeds, for example to control the growth of those species hereinbefore mentioned, by pre- or post- emergence application in a directional or non- directional fashion, e.g. by directional or non- directional spraying, to a locus of weed infestation which is an area used, or to be used, for growing crops, for example cereals, e.g. wheat, barley, oats, maize and rice, soya beans, field and dwarf beans, peas, lucerne, cotton, peanuts, flax, onions, carrots, cabbage, oilseed rape, sunflower, sugar beet, and permanent or sown grassland before or after sowing of the crop or before or after emergence of the crop. For the selective control of weeds at a locus of weed infestation which is an area used, or to be used, for growing of crops, e.g. the crops hereinbefore mentioned, application rates between 10 g and 500 g, and preferably between 25 g and 250 g, of active material per hectare are particularly suitable.
The compounds of the invention are especially useful for controlling grass weed species .
The compounds of the invention are also useful for the control of weeds in rice crops grown in paddy field water. The compounds of formula (I) may for example be added to the paddy field water .
The compounds of formula I may also be used to control the growth of weeds, especially those indicated above, by pre- or post-emergence application in established orchards and other tree-growing areas, for example forests, woods and parks, and plantations, e.g. sugar cane, oil palm and rubber plantations . For this purpose they may be applied in a directional or non- directional fashion (e.g. by directional or non- directional spraying) to the weeds or to the soil in which they are expected to appear, before or after planting of 'the trees or plantations at application rates between 50 g and 2000 g, and preferably between 50 g and 1000 g, most preferably between 100 g and 500 g of active material per hectare.
The compounds of formula I may also be used to control the growth of weeds, especially those indicated above, at loci which are not crop- growing areas but in which the control of weeds is nevertheless desirable.
Examples of such non-crop-growing areas include airfields, industrial sites, railways, roadside verges, the verges of rivers, irrigation and other waterways, scrublands and fallow or uncultivated land, in particular where it is desired to control the growth of weeds in order to reduce fire risks. When used for such purposes in which a total herbicidal effect is frequently desired, the active compounds are normally applied at dosage rates higher than those used in crop-growing areas as hereinbefore described. The precise dosage will depend upon the nature of the vegetation treated and the effect sought.
Pre- or post-emergence application, and preferably pre-emergence application, in a directional or non-directional fashion (e.g. by directional or non-directional spraying) at application rates between 50 g and 2000 g, and preferably between 50 g and 1000 g, most preferably between 100 g and 500 g of active material per hectare are particularly suitable for this purpose . When used to control the growth of weeds by pre-emergence application, the compounds of formula I may be incorporated into the soil in which the weeds are expected to emerge. It will be appreciated that when the compounds of formula I are used to control the growth of weeds by post-emergence application, i.e. by application to the aerial or exposed portions of emerged weeds, the compounds of formula I will also normally come into contact with the soil and may also then exercise a pre-emergence control on later-germinating weeds in the soil. Where especially prolonged weed control is required, the application of the compounds of formula I may be repeated if required. TEST METHOD
Paddy post-emergence application in greenhouse Paddy field soil was filled in 170 cm^ plastic pots, a suitable amount of water and chemical fertilisers were added thereto and kneaded to convert it to a state of a paddy. Paddy rice plants (variety; Koshihikari) , that had been grown in advance in a greenhouse to a stage of two leaves, were transplanted to each pot (two seedlings per pot) . Then in each pot there were sown predetermined amounts of seeds of Echinochloa oryzicola, Monochoria vaginalis, Lindernia procumbens and Scirpus juncoides respectively, and water was added to a depth of 3 cm.
After having grown the plants in a greenhouse until Echinochloa oryzicola reached a stage of 1.5 leaves, solutions were prepared in 100% acetone using compounds described in the Examples so that they contained active ingredients in an amount equivalent to 75, 300 and 1200 g/ha. The solutions were applied to the water by dropping with a pipette.
After 21 days from the application with the chemicals, herbicidal effects on each weed and phytotoxicity on paddy rice plants were visually assessed, and the results expressed as the percentage reduction in growth or damage to the crop or weeds in comparison with the plants in the control pots. When applied at 1200 g/hectare or less in the above Test Method , compounds 1-22, 24-29, 138, 139, 143, 157, 158, 162, 165, 167, 169, 176, 177, 181, 184 and 290-384 of the invention gave at least 80% reduction in growth of one or more of the weed species listed above.

Claims

1. A cyclic amide derivative of formula (I) :
Figure imgf000071_0001
(I) wherein:
X represents -S(0)v-, an oxygen atom or -NR12 ;
Y represents -O- or -CH2-; R1 represents phenyl, benzyl or thienyl optionally substituted by one to five groups which may be the same or different selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, -C02R6, -COR6, cyano, nitro, -O (CH2 ) q-CC^R6 and phenoxy; or alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl or cycloalkyl;
R2 represents hydrogen, alkyl, haloalkyl, alkoxyalkyl , haloalkoxyalkyl , alkenyl , haloalkenyl , alkynyl , haloalkynyl , alkoxyalkenyl, -CHO, -COR6, -C02R6 , -CH2N02 , cyano, -C02H, -COSR6 , -CONR7R8, -CH=N0H, -CH=N0R6, -CH=NOCOR6, -CH=NNR7R8 , -CH2CN, -CH2NO2 or oxiranyl ; or alkyl which is substituted by a group selected from -S(0)nR6, OH, -OCOR6, -NR7R8 and azido;
R3 represents CONHR9, COR10; CO2R11; or phenyl optionally substituted by one to five groups which may be the same or different selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, -CO2R6 , -COR6, cyano, nitro, -0 (CH2 ) g _Cθ2R6 and phenoxy;
R4 and R^ independently represent alkyl;
R6 represents alkyl or haloalkyl; R7 and R8 independently represent hydrogen, alkyl or haloalkyl;
R9 represents phenyl optionally substituted by from one to five groups which may be the same or different selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, -CO2R6, -COR6, cyano, nitro, -NR7R8 , phenoxy, -0(CH2)q-C02R6 and -SF5;
R10 represents - (CR13R14 ) r- (phenyl or naphthyl optionally substituted by from one to five groups which may be the same or different selected from halogen, hydroxy, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, -CO2R6, -COR6, cyano, nitro, -0 (CH2 ) qCθ2R6 , phenoxy, -SF5, -OCOR6, NR15R16, NHR17 , -CH2NR15R16,
-CONR15R16, -CONHR17, -OS02R6 , -OS02R17 , -OCOR17, -OCH2COR17, -OCH2R17, -S(0)mR17, R17 , -P(=0) (OR6) (OR18) , -P(=0) (OR6)R18 , -CH2P(=0) (OR6) (OR18) , -CH2P(=0) (OR6)R18, -C02R17, -CH2S(0)nR6, -CH2S(0)mR17, -CH2OR6 ,
-CH20R17, -CH20C0R17, -CH2OS02R17 and alkenyl); or represents a phenyl ring optionally substituted by from one to four groups which may be the same or different selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, CN and NO2 , and which is fused to a second five or six membered cycloalkyl or cycloalkenyl ring, or to a saturated five or six membered heterocyclic ring (for example to give a 1,3- benzodioxole or 1, 4-benzodioxane ring) which contains one to three heteroatoms which may be the same or different selected from nitrogen, oxygen and sulphur, said ring systems being optionally substituted by one or more groups R19 or optionally one of the carbon atoms in the cycloalkyl, cycloalkenyl or saturated five or six membered heterocyclic ring may form a carbonyl group (for fused ring systems it is the phenyl ring which is linked to the carbonyl group which forms part of -C"( =0) R1 ) ,- or represents a phenanthrene or anthracene ring optionally substituted by one or more groups selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, CN and N02 ; or represents - (CH2) s- ( five to seven membered heteroaromatic ring having from one to four ring heteroatoms which may be the same or different selected from nitrogen, oxygen and sulphur, said ring being optionally fused to a phenyl ring or to a second five to seven membered heteroaromatic ring having from one to four heteroatoms v/hich may be the same or different selected from nitrogen, oxygen and sulphur, to form a bicyclic ring system, the monocyclic ring or either ring in the bicyclic system being optionally substituted by from one to four groups which may be the same or different selected from halogen, hydroxy, alkyl, cyano, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, -CO2 6, -COR6, nitro, -0 (CH2 ) qCθ2R6 and phenoxy) ; or represents cycloalkyl containing from three to eight carbon atoms or cycloalkenyl containing four to eight carbon atoms, wherein the ring systems are optionally substituted by one or more groups selected from R19, CO2H, CO2R , alkenyl, haloalkenyl, R17 , alkoxy, haloalkoxy, S(0)nR6, COR6, COR17, CH2COR17, COCH2R17 , C02CH2R17, S(0)mR17, CN, S(0)tCH2R17, S(0)uR2°,
CH OR6, CHO, COR21, CONHR17, CONR6R17 , CH20H, -CH(OR22) (OR23) (optionally the group -CH(OR22) (OR23 ) represents a five or six membered cyclic acetal optionally substituted by one or more R6 groups) , or one of the cycloalkyl carbon atoms forms part of a carbonyl group; or represents cycloalkyl containing from five to seven carbon atoms or cycloalkenyl containing five or six carbon atoms, the ring systems of which are optionally substituted by one or more groups R19, and wherein the ring systems are fused to a phenyl ring (for example indanyl) optionally substituted by from one to four groups which may be the same or different selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR°, cyano or nitro (for fused ring systems it is the cycloalkyl or cycloalkenyl ring which is linked to the carbonyl group which forms part of the -C(=0)R 0 group) ; or represents alkyl, haloalkyl, alkenyl, haloalkenyl or alkynyl which are optionally substituted by one or more groups selected from -OH, -OR6, -S(0)nR6, -S(0)mR17, -C02R6 , -C02CH2R17, CN, N02, CHO, COR6, COR17, C0CH R17 , -C02H, -CONR15R16, -S(0)tCH2R17, -S(0)pR24, R1 , a three to six membered cycloalkyl ring optionally substituted by one or more R1^ groups, a five or six membered cyclic acetal group optionally substituted by one or more R6 groups, and a thienyl or furyl ring optionally substituted by one or more groups R19; R11 represents alkyl, haloalkyl, cycloalkyl; or phenyl optionally substituted by one or more groups selected from halogen, alkyl and haloalkyl ;
R12 represents hydrogen, alkyl, haloalkyl, alkenyl, haloalkenyl, alkynyl, haloalkynyl or cycloalkyl;
R13, R! ( R15 and R16 independently represent hydrogen, alkyl or haloalkyl; R17 represents phenyl optionally substituted by one or more groups which may be the same or different selected from halogen, alkyl, haloalkyl, alkoxy, haloalkoxy, -S(0)nR6, cyano and nitro; R18 represents alkyl or haloalkyl;
R19 represents halogen, alkyl or haloalkyl;
R2 represents cycloalkyl containing from three to seven carbon atoms optionally substituted by one or more groups R19;
R21 represents cycloalkyl containing from three to seven carbon atoms or cycloalkenyl containing five or six carbon atoms, wherein the ring systems are optionally substituted by one or more groups R19;
R22 and R23 represent alkyl or the group -CH(OR22) (OR23)- represents a five or six membered cyclic acetal, namely a 1, 3-dioxolane or 1,3-dioxane ring of formula -CH(OR22a) (OR23a)- wherein R22a and R23a together represent a C2 or C3 alkylene chain which is optionally substituted by alkyl or haloalkyl ;
R24 represents cycloalkyl containing from three to seven carbon atoms optionally substituted by one or more groups R19 ; m, n, p, t, u and v represent zero, one or two; q represents one or two; r and s represent zero or one; or an agriculturally acceptable salt thereof.
2. A compound according to claim 1 in which X represents -S(0)v- and v represents zero .
3. A compound according to claim 1 or 2 in which R1 represents alkyl or haloalkyl .
4. A compound according to claim 1, 2 or 3 in which R2 represents hydrogen, methyl or ethyl .
5. A compound according to any one of the preceding claims in which R3 represents CONHR9 in which R9 represents phenyl optionally substituted by one to three groups which may be the same or different selected from halogen, alkyl, haloalkyl and nitro; or R3 represents COR10 in which R1 represents cycloalkyl containing from three to six carbon atoms or cycloalkenyl containing five or six carbon atoms, the ring systems of which are optionally substituted by a group R19; or R1 represents an optionally halogenated alkyl group containing up to four carbon atoms which is substituted by cycloalkyl containing from three to six carbon atoms (the cycloalkyl ring is optionally substituted by one or more halogen or alkyl groups); or R10 represents -CH2- (phenyl substituted by one to three groups selected from halogen, methyl and trifluoromethyl) .
6. A compound according to any one of the preceding claims in which R4 and R^ represent methyl .
7. A compound according to any one of the preceding claims in which Y represents -O- .
8. A compound according to any one of claims 1, 5, 6 and 7 wherein:
X represents -S-, -O- or NR12 in which R12 represents hydrogen or alkyl ; Y represents -O- ;
R1 represents phenyl which is optionally substituted by one to three groups which may be the same or different selected from halogen, alkyl and haloalkyl ; or represents alkyl or haloalkyl;
R2 represents hydrogen, alkyl or haloalkyl;
R represents CONHR9 in which R9 represents phenyl optionally substituted by one to three groups which may be the same or different selected from halogen, alkyl, haloalkyl and nitro; or R3 represents COR1 in which R1 represents cycloalkyl containing from three to six carbon atoms, the ring system of which is optionally substituted by a group R19; or R10 represents an optionally halogenated alkyl group containing up to four carbon atoms which is substituted by cycloalkyl containing from three to six carbon atoms (the cycloalkyl ring is optionally substituted by one or more halogen or alkyl groups); or R1 represents -CH2- (phenyl substituted by one to three groups selected from halogen, methyl and trifluoromethyl) ; and R4 and R^ represent methyl.
9. A compound according to any one of the preceding claims wherein:
X represents -S-;
Y represents -0- ; R1 represents alkyl or haloalkyl;
R2 represents hydrogen, methyl or ethyl;
R3 represents CONHR9 in which R9 represents phenyl substituted by one to three groups which may be the same or different selected from halogen, methyl and trifluoromethyl; or R3 represents COR1 in which R10 represents cycloalkyl containing from three to six carbon atoms optionally substituted by alkyl; or R10 represents an optionally halogenated alkyl group containing up to four carbon atoms which is substituted by cycloalkyl containing from three to six carbon atoms (the cycloalkyl ring is optionally substituted by an alkyl group) ; and
R4 and R5 represent methyl .
10. A herbicidal composition comprising an effective amount of a cyclic amide derivative according to any one of claims 1 to 9 or an agriculturally acceptable salt thereof, in association with an agriculturally acceptable diluent or carrier and/or surface active agent.
11. A method for the control of weeds at a locus which comprises applying to said locus an effective amount of a cyclic amide derivative according to any one of claims 1 to 9 or an agriculturally acceptable salt thereof or a herbicidal composition according to claim 10.
12. A method according to claim 11 wherein the locus is an area used, or to be used, for the growing of crops and the cyclic amide derivative or salt thereof is applied at an application rate of from 1 g to 1000 g/ha.
13. A process for the preparation of a cyclic amide derivative of formula (I) as defined in claim 1 which comprises:
(a) where R3 is -CONHR9, the reaction of a compound of formula (II):
Figure imgf000078_0001
wherein R1, X, Y, R2 , R4 and R5 are as defined in claim 1, with an amine of formula (III) :
R9NH2 (III) wherein R9 is as defined in claim 1;
(b) where R9 is - CONHR9 , the re compound of formula (IV) :
Figure imgf000078_0002
(IV) wherein R1, X, Y, R2 , R4 and R5 are as defined in claim 1, with an amine of formula (III) above and a coupling reagent;
(c) where R3 represents CO2R11, the reaction of a compound of formula (II) above wherein R1, X, Y, R2 , R4 and R5 are as defined in claim 1, with a compound of formula (V) : R1:LOH (V) wherein R11 is as defined in claim 1 ; (d) where R3 represents COR10 , and X is an oxygen atom or NR1 , the oxidation of the corresponding compound of formula (VI) :
(VI) wherein RJ Y, R2, R4, R5 and R10 are as defined in claim 1 and X is an oxygen atom or NR12 ;
(e) where Y is an oxygen atom and R1, X, R2, R3, R4 and R5 are as defined in claim 1, the reaction of a compound of formula (VII) :
Figure imgf000079_0002
(VII) wherein R1, X and R2 are as defined in claim
Figure imgf000079_0003
(VIII) wherein R3 , R4 and R^ are as defined in claim 1;
(f) where Y is an oxygen atom and R1, X,
R2 , R3 , R4 and R5 are as defined in claim 1, the reaction of a compound of formula (IX) :
R2C(0)-CH(XR1)-C02R (IX) wherein R1, X and R2 are as defined in claim 1 and R represents an alkyl group, with an imine of formula (VIII) above; (g) where R1, X, R2 , R3 , R4 and R5 are as defined in claim 1 and Y is -CH2~, the reaction of a compound of formula (X) :
Figure imgf000080_0001
(X) wherein R1, X, R2 , R3 , R4 and R5 are as defined in claim 1, with a base; and
(h) where m, n, p, t, u or v represent one or two, the oxidation of the sulphur atom of the corresponding compounds in which m, n, p, t, u or v represent zero or one; optionally followed by the conversion of the compound of formula (I) thus obtained into an agriculturally acceptable salt thereof.
14. A compound of formula (II), (IV), (VI), (X) and (XII) :
Figure imgf000080_0002
(VI) (X)
Figure imgf000080_0003
(XII) wherein the various substituents are as defined in any one of the previous claims.
PCT/EP1999/008305 1998-10-26 1999-10-20 2,3-dihydro-4-oxo-4h-1,3-oxazine and 2-oxo-1,2,5,6-tetrahydropyridine derivatives and their use as herbicides WO2000024722A1 (en)

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GB9823429A GB2343179A (en) 1998-10-26 1998-10-26 Oxazinone and pyridone herbicides

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7521473B2 (en) 2004-02-25 2009-04-21 Wyeth Inhibitors of protein tyrosine phosphatase 1B

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0489485A (en) * 1990-07-30 1992-03-23 Daicel Chem Ind Ltd 1,3-oxazin-4-one derivative, its production and plant growth inhibitor
WO1995018113A1 (en) * 1993-12-24 1995-07-06 Mitsubishi Chemical Corporation 1,3-oxazin-4-one derivatives, process and intermediates for their preparation and their use as herbicides
WO1997021688A1 (en) * 1995-12-11 1997-06-19 Rhone-Poulenc Agriculture Ltd. 1,3-oxazin-4-one derivatives as herbicides

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH0489485A (en) * 1990-07-30 1992-03-23 Daicel Chem Ind Ltd 1,3-oxazin-4-one derivative, its production and plant growth inhibitor
WO1995018113A1 (en) * 1993-12-24 1995-07-06 Mitsubishi Chemical Corporation 1,3-oxazin-4-one derivatives, process and intermediates for their preparation and their use as herbicides
WO1997021688A1 (en) * 1995-12-11 1997-06-19 Rhone-Poulenc Agriculture Ltd. 1,3-oxazin-4-one derivatives as herbicides

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
CHEMICAL ABSTRACTS, vol. 117, no. 9, 31 August 1992, Columbus, Ohio, US; abstract no. 90305q, GOTO Y ET AL: "Preparation of 1,3-oxazin-4-one derivatives as plant growth inhibitors." page 785; column 2; XP002130488 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7521473B2 (en) 2004-02-25 2009-04-21 Wyeth Inhibitors of protein tyrosine phosphatase 1B

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