WO1995032952A1 - Procede de preparation de 3-aryluraciles - Google Patents

Procede de preparation de 3-aryluraciles Download PDF

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WO1995032952A1
WO1995032952A1 PCT/EP1995/001875 EP9501875W WO9532952A1 WO 1995032952 A1 WO1995032952 A1 WO 1995032952A1 EP 9501875 W EP9501875 W EP 9501875W WO 9532952 A1 WO9532952 A1 WO 9532952A1
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formula
compound
process according
methyl
preparation
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PCT/EP1995/001875
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Walter Kunz
Urs Siegrist
Peter Baumeister
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Ciba-Geigy Ag
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and unsaturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
    • C07D263/52—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings condensed with carbocyclic rings or ring systems
    • C07D263/54—Benzoxazoles; Hydrogenated benzoxazoles
    • C07D263/58—Benzoxazoles; Hydrogenated benzoxazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • 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
    • C07D265/28—1,4-Oxazines; Hydrogenated 1,4-oxazines
    • C07D265/34—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings
    • C07D265/36—1,4-Oxazines; Hydrogenated 1,4-oxazines condensed with carbocyclic rings condensed with one six-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/60—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings condensed with carbocyclic rings or ring systems
    • C07D277/62—Benzothiazoles
    • C07D277/68—Benzothiazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D279/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one sulfur atom as the only ring hetero atoms
    • C07D279/10—1,4-Thiazines; Hydrogenated 1,4-thiazines
    • C07D279/14—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems
    • C07D279/16—1,4-Thiazines; Hydrogenated 1,4-thiazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/02—Systems containing only non-condensed rings with a three-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/04—Systems containing only non-condensed rings with a four-membered ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/18—Systems containing only non-condensed rings with a ring being at least seven-membered

Definitions

  • the present invention relates to a novel process for the preparation of 3-phenyluracils and to the use of certain aromatic amino compounds as intermediates in the preparation of those 3-phenyluracils.
  • 3-Phenyluracils can be prepared, for example, by formation of the uracil ring from open-chained aniline derivatives that already have the desired substitution pattern. For example, it is known from US-A-5 183 492 to prepare 3-phenyluracils of formula VIII
  • R 10 is C 1 -C 4 alkyl, C 3 -C 4 alkenyl or C 3 -C 4 alkynyl;
  • R 11 is C 1 -C 4 alkyl or C 1 -C 4 haloa ⁇ kyl
  • R 13 is hydrogen, halogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, cyano or hydroxy;
  • R 12 is hydrogen, fluorine or chlorine
  • R 14 is (C 3 -C 6 alkenyloxy)carbonyl-C 1 -C 4 alkyl
  • R 11 is C 1 -C 4 alkyl and R 12 , R 13 , R 14 and R 15 are as defined above, subjecting that compound to cyclisation under basic conditions and then alkylating the 1-position of the resulting 3-phenyluracil, or
  • R 12 , R 13 and R 14 are as defined above, or with a compound of formula Xllla
  • R 12 and R 13 are as defined above, into the compound of formula XI wherein R 11 is C 1 -C 4 haloalkyl and R 12 , R 13 , R 14 and R 15 are as defined above, subjecting that compound to cyclisation under basic conditions, and then alkylating the 1-position of the resulting 3-phenyluracil.
  • 3-phenyluracils can be prepared in an especially advantageous manner by using as starting compound, instead of an aminocarbonylaminophenyl derivative of formula IX or an isocyanatophenyl derivative of formula XIII or an alkyloxycarbonylaminophenyl derivative of formula Xllla, an aniline compound obtained by reduction of a corresponding nitrophenyl derivative, and converting that aniline compound with a ⁇ -keto ester or a ⁇ -ketocarboxylic acid halide into an acetoacetanilide which is then converted with an ammonium salt into an enamine, from which the compound of formula I is obtained after cyclisation and alkylation.
  • R is the group -(Y-Q) m -[C(O)] n -X-R 2 ;
  • R 1 is C 1 -C 4 alkyl, C 3 -C 4 alkenyl or C 3 -C 4 alkynyl;
  • R 2 is C 3 -C 6 alkenyl, C 3 -C 6 alkynyl, C 3 -C 8 cycloalkenyl, C 6 -C 8 bicycloalkenyl or
  • R 3 is hydrogen, halogen, C 1 -C 3 alkyl, C 1 -C 3 alkoxy, C 1 -C 3 haloalkyl, C 1 -C 3 haloalkoxy, cyano or hydroxy; or
  • R 3 and R together form the group -N(R 17 )-C(O)-(CH 2 ) n1 -X 3 -;
  • R 4 is hydrogen, fluorine or chlorine
  • R 5 is C1-C 4 alkyl, C 1 -C 4 haloalkyl, C 3 -C 6 alkenyl or C 3 -C 6 alkynyl;
  • Y is oxygen, sulfur, N-R 6 or C(O)-X 1 ;
  • X is oxygen, sulfur or N-R 7 ;
  • X 1 is oxygen, sulfur or N-R 8 ;
  • R 6 , R 7 and R 8 are each independently of the others C 1 -C 4 alkyl, C 1 -C 4 haloalkyl,
  • n 0 or 1 ;
  • n 0 or 1 ;
  • Q is a C 1 -C 10 alkylene group the carbon atoms of which are capable of forming a 1,1- or 1,2-linked C 3 -C 8 cycloalkyl ring;
  • n 1 is 0 or 1
  • X 3 is oxygen or sulfur
  • R 17 is C 3 -C 6 alkenyl or C 3 -C 6 alkynyl
  • R, R 3 and R 4 are as defined for formula I, in the presence of a catalyst containing platinum modified by lead, mercury, bismuth, germanium, cadmium, arsenic, antimony, silver or gold, to a compound of formula VI
  • R, R 3 and R 4 are as defined for formula I, b) reacting that compound with a compound of formula V wherein R 5 is as defined for formula I and R 9 is chlorine or C 1 -C 4 alkoxy, in an aprotic solvent, to form a compound of formula IV
  • R, R 3 , R 4 and R 5 are as defined for formula I, c) converting that compound in the presence of an enaminating agent, such as ammonia, but preferably in the presence of an ammonium salt of a carboxylic acid, into the compound of formula III
  • R, R 3 , R 4 and R 5 are as defined for formula I, d) reacting that compound in the presence of a base and an inert solvent with a compound of formula IlIa
  • L 1 and L 2 are each independently of the other halogen, C 1 -C 4 alkoxy, imidazol-1-yl or 1,2,4-triazol-1-yl, to form the compound of formula II
  • R, R 3 , R 4 and R 5 are as defined for formula I, and e) converting that compound in an inert solvent in the presence of a base with a compound of formula IIa
  • alkyl is, for example, methyl, ethyl, isopropyl, n-propyl, n-butyl, isobutyl, sec -butyl or tert-butyl.
  • Haloalkyl is, for example, fluoromethyl, difluoromethyl, trifluoromethyl, chloromethyl, dichloromethyl, trichloromethyl, 2,2,2-trifluoroethyl, 2-fluoroethyl, 2-chloroethyl, 2,2,2-trichloroethyl or pentafluoroethyl; preferably trichloromethyl, difluorochloromethyl, trifluoromethyl or dichlorofluoromethyl.
  • Alkenyl is to be understood as being straight-chained or branched alkenyl, such as allyl, methallyl, 1-methylvinyl, but-2-en-1-yl, pentenyl or 2-hexenyl.
  • alkynyl groups mentioned in the definitions of the substituents may be straight- chained or branched, such as propargyl, 3-butynyl, 1-methylpropargyl, 1-pentynyl or 2-hexynyl.
  • Alkoxy is, for example, methoxy, ethoxy, propyloxy or isopropyloxy.
  • halogen is to be understood to be fluorine, chlorine, bromine or iodine, preferably fluorine, chlorine or bromine.
  • Cycloalkenyl is, for example, cyclobutenyl, cyclopentenyl, 3-methylcyclopentenyl or cyclohexenyl.
  • Q as a C 1 -C 10 alkylene group is, for example, -CH 2 -, -CH 2 -CH 2 -, -CH 2 -CH 2 -CH 2 -, -C H 2 -CH 2 -CH 2 -CH 2 , -CH 2 -CH 2 -CH 2 -CH 2 -CH 2 , -CH 2 -CH 2 -CH 2 -CH 2 -CH 2 -CH 2 , -CH 2 -CH(CH 3 )-CH 2 -CH 2 -CH 2 -CH 2 , -CH(CH 3 )-, -C(CH 3 ) 2 -, -CH(CH 3 )-CH 2 -, -CH(CH 3 )-CH 2 -,
  • Q as a C 1 -C 10 alkylene group the carbon atoms of which form a 1,1- or 1,2-linked C 3 -C 8 cycloalkyl ring is, for example,
  • R and R 3 together form the group -N(R 17 )-C(O)-(CH 2 ) n1 -X 3 -, that group is linked in such a manner that -N(R 17 )- occupies the 3-position of R and -X 3 - the 4-position of R 3 on the phenyl ring.
  • optically active compounds of formula I can be obtained from the racemic mixtures by known separating methods, such as fractional crystallisation.
  • the compounds of formula I are to be understood to include both the pure optical antipodes and the racemates or diastereo- isomers. Unless specific reference is made to the individual optical antipodes, the formula indicated is to be understood to represent the particular racemic mixtures that are obtained by the preparation process indicated.
  • n 1 is 0; and X 3 is sulfur.
  • n 1 is 1; and X 3 is oxygen.
  • R and R 3 together form the group -N(R 17 )-C(O)-(CH 2 ) n1 -X 3 -;
  • R 17 is allyl, methallyl, propargyl or 1-methylpropargyl.
  • R and R 3 together form the group -N(R 17 )-C(O)-(CH 2 ) n1 X 3 -;
  • R 1 is methyl;
  • R 4 is hydrogen or fluorine; and
  • R 5 is C 1 -C 4 haloalkyl; especially those wherein R 5 is trifluoromethyl, trichloromethyl, difluorochloromethyl, difluoromethyl or pentafluoroethyl.
  • the process according to the invention is especially suitable for the preparation of compounds of formula I wherein R 3 is halogen.
  • the process according to the invention is especially suitable for the preparation of
  • JP 82 120 553 discloses the preparation of aromatic amines that can be substituted by groups having unsaturated carbon-carbon bonds, by hydrogenating the corresponding nitro compounds in the presence of a palladium catalyst and in the presence of a carboxylic acid, such as dinitrobenzoic acid.
  • a carboxylic acid such as dinitrobenzoic acid.
  • the promotors can either be added to the reaction mixture directly in the form of salts or deposited as an insoluble compound on the surface of the catalysts during the preparation or the modification thereof.
  • Preferred promotors that can be used in the catalysts are: Fe 2+ , Fe 3+ , Ru 3+ , Mn 2+ and Mn 3+ in the form of salts with the anions Cl-, Br-, F-, SO 4 2- , NO 3 - acetate, citrate, gluconate, lactate, oxalate, benzoate, naphthenate, tartrate and formate, or in the form of a suitable metal complex.
  • the hydrogenation can be accelerated using a co-promotor.
  • Suitable as co-promotors are salts or pairs of ions that are generally soluble in organic solvents, especially ionophores known from electrochemistry, for example in the form of a cation (C 1 -C 6 alkyl) 4 N + or lk yl or in the form of an anion Cl-,
  • the promotor is preferably used in an amount of from 0.001 to 10 % by weight, based on the compound of formula VII used, there being used as promotor especially an iron salt, most especially FeCl 2 •4H 2 O.
  • the modifying metal used for the platinum catalyst is preferably lead, especially in the form of lead acetate, lead nitrate, lead chloride or tetraalkylene lead, such as tetraethyl lead.
  • the catalyst is used preferably in an amount of from 0.1 to 5 % by weight, based on the compound of formula VII that is used, the ratio by weight of platinum to modifying metal being from 1 : 0.001 to 1 : 1, preferably from 1 : 0.1 to 1 : 0.5.
  • platinum to be modified can be used in the form of platinum black, platinum oxide or preferably in metallic or oxidised form applied to a carrier.
  • Carriers that are especially suitable are activated carbon, silicic acid, silica gel, aluminium oxide, calcium carbonate, calcium phosphate, calcium sulfate, barium sulfate, titanium oxide, magnesium oxide, iron oxide, lead oxide, lead sulfate or lead carbonate, preferably activated carbon, aluminium oxide or calcium carbonate.
  • Platinum applied to the above- mentioned carrier material is commercially available or can be prepared by methods familiar to a person skilled in the art, such as those disclosed, for example, in
  • Process step a) of the process according to the invention is carried out under a pressure of from 1 to 100 bar and at a temperature of from +20 to +160°C, preferably under a pressure of from 20 to 40 bar and at a temperature of from +100 to +140°C.
  • Preferred solvents are water, alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol, the isomers of butanol and cyclohexanol, ethers, esters and ketones, such as diethyl ether, methyl tert-butyl ether, tetrahydrofuran, dioxane, dimethoxyethane, ethyl acetate, butyl acetate, butyrolactone, acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, carboxylic acids, such as acetic acid and propionic acid, dipolar aprotic solvents, such as dimethylformamide, N-methyl- pyrrolidone, dimethylacetamide, sulfolane, dimethyl sulfoxide or acetonitrile, non-polar solvents, such as tolu
  • solvents can be used in pure form or as mixtures.
  • the reaction according to process step a) is preferably carried out in the liquid phase, especially with a pulverulent catalyst, either continuously or discontinuously as a semi-solid-phase hydrogenation, or in a bubble column, or with a shaped catalyst in a trickle bed.
  • the reaction can also be carried out in the gas phase with a pulverulent catalyst in a fluidised bed or with a shaped catalyst in a fixed bed.
  • Suitable aprotic solvents for process step b) are, for example, aromatic hydrocarbons, such as benzene and toluene, or hydrocarbons, such as hexane, cyclohexane, halogenated hydrocarbons, such as trichloromethane, 1,1,1-trichloroethane or 1,2-dichloroethane, or ethers, such as diisobutyl ether, tetrahydrofuran or 1,4-dioxane.
  • aromatic hydrocarbons such as benzene and toluene
  • hydrocarbons such as hexane, cyclohexane
  • halogenated hydrocarbons such as trichloromethane, 1,1,1-trichloroethane or 1,2-dichloroethane
  • ethers such as diisobutyl ether, tetrahydrofuran or 1,4-dioxane.
  • process step b) can be carried out in the presence of a base.
  • bases are, for example, oxides, carbonates of an alkali metal or alkaline earth metal, such as sodium carbonate, alkali metal alkoxides, such as potassium tert-butoxide, amines, such as trialkylamines, for example triethylamine or triethanolamine, or pyridine bases, such as dimethylaminopyridine.
  • reaction of compounds of formula V wherein R 9 is C 1 -C 4 alkoxy is carried out preferably at temperatures of from 0 to 180°C, preferably at from 60 to 130°C, especially under reflux, it being very especially preferred to remove the resulting alcohol, for example by azeotropic distillation.
  • the reaction of compounds of formula V wherein R 9 is chlorine is preferably carried out with cooling at temperatures of from -40 to +150°C, preferably from -20 to +80°C.
  • Base-catalysed reactions of ⁇ -keto esters wherein R 5 is other than haloalkyl, in which the resulting alcohol is not, however, removed by azeotropic distillation are described, for example, in Synthesis, 1988, 753.
  • reaction according to process step b) also leads to a high yield of the desired product of formula IV when R 5 is a strongly electron-attracting substituent, such as CF 3 or CCl 3 . In the knowledge of the prior art, that course of the reaction was not to be expected.
  • US-A-2 857 373 describes the preparation of trifluoroacetoacetanilide in a yield of only 45 % by heating 1,1,1-trifluoroacetoacetic acid ethyl ester with aniline in boiling xylene with simultaneous removal of the alcohol formed.
  • T 1 and T 2 are reagents for introducing a leaving group L 4 or L 5 , respectively (e.g. SOCl 2 ,
  • L 4 and L 5 are each independendy of the other halogen (esp. Cl), O-COalkyl C 1 -C 4 or imidazol-1'-yl.
  • reaction steps can be carried out, for example, as follows: XIV ⁇ XVa:
  • the carboxylic acid XIV is converted in an inert solvent at from -20 to +150°C (preferably from 0 to +100°C) with a suitable reagent T 1 into the activated acid derivative XVa.
  • the compound of formula XVa is reacted in the presence of a base (see below) in an inert solvent at from -10 to +150°C, preferably from 0 to +100°C, with an acid derivative XVI to form XVIIa.
  • the acid XIV can alternatively be reacted with the alcohol XVI by acid-catalysed esterification in an inert solvent at from -10 to +150°C to form XVIIa.
  • acid catalysts for example, H 2 SO 4 , HCl, H 3 PO 4 and BF 3 OEt 2 .
  • water of reaction that is formed can be removed continuously from the reaction mixture, for example by azeotropic distillation in a solvent, such as toluene or xylene.
  • 1,1,1-trichloroethane or dichloromethane at a temperature of from -20 to +150°C, preferably from 0 to +100°C, to form XVIIIa.
  • HXR 2 (XIX) is converted in an inert solvent and in the presence of a base at a temperature of from -20 to +150°C (preferably from 0° to +60°C) into the acid derivative of formula Vllb.
  • a catalyst such as 4-dimethylaminopyridine
  • the activated acid derivative XVa can be reacted with an intermediate XX directly to Vllb in the presence of a base in an inert organic solvent at a temperature of from -20 to +150°C, preferably from 0° to +60°C, if appropriate with the addition of a catalyst, such as 4-dimethylaminopyridine.
  • a catalyst such as 4-dimethylaminopyridine.
  • Suitable bases are, for example, alkali metal and alkaline earth metal carbonates
  • alkaline earth metal oxides such as CaO
  • tertiary amines such as trialkylamines (NEt 3 )
  • pyridine bases such as pyridine, collidine or quinoline.
  • the reactions can be carried out under the conditions of phase-transfer catalysis.
  • ammonium acetate as the ammonium salt, especially in an amount of from 1 to 20 equivalents, preferably from 1 to 10 equivalents.
  • the reaction can, if desired, be carried out in an aprotic solvent, such as ethyl acetate, diisopropyl ether, tetrahydrofuran, dioxane, cyclohexane, toluene or a mixture thereof, under normal pressure or under elevated pressure.
  • water that is formed can be removed under reflux with a drying agent, such as calcium chloride, or a molecular sieve, or by azeotropic distillation.
  • reaction step c) is carried out in the presence of ammonium acetate either in an aprotic solvent or in the melt in the absence of a solvent.
  • the reaction temperatures are dependent on the choice of solvent and are in the range of from 0 to 180°C, preferably from 50 to 140°C; when using ammonium acetate in the melt they are preferably in the range of from 100 to 130°C. Lower melting points can be achieved, for example, by adding small amounts of inert solvents, such as ethyl acetate.
  • the compounds of formula IV and the compounds of formula III prepared therefrom are novel and the present invention relates also thereto.
  • organic or inorganic acids such as hydrochloric acid, sulfuric acid, oxalic acid, benzoic acid or p-toluenesulfonic acid, or sodium hydrogen sulfate or potassium hydrogen phosphate can be added.
  • organic or inorganic acids such as hydrochloric acid, sulfuric acid, oxalic acid, benzoic acid or p-toluenesulfonic acid, or sodium hydrogen sulfate or potassium hydrogen phosphate
  • Suitable bases are especially organic bases, such as triethylamine, quinoline or pyridine, or mixtures, such as pyridine with 4-dimethylaminopyridine or quinoline.
  • H- L 1 or H-L 2 scavengers such as epoxides, for example propylene oxide.
  • Suitable inert solvents are aromatic hydrocarbons, such as benzene and toluene, or halogenated hydrocarbons, such as dichloromethane or 1,1,1-trichloroethane. The use of toluene is preferred.
  • the reaction temperatures are in the range of from -20 to + 160°C, preferably from 0 to 100°C. The reactions can be carried out under normal pressure or under elevated pressure.
  • Suitable inert solvents in process step e) are especially protic solvents, such as
  • C 1 -C 4 alcohols for example ethanol, or aprotic solvents, such as aliphatic or cyclic ethers, such as 1,2-dimethoxyethane, tetrahydrofuran and dioxane, aliphatic ketones, such as acetone, nitriles, such as acetonitrile, amides, such as dimethylformamide, N-methylpyrrolidone, or sulfoxides, such as dimethyl sulfoxide.
  • aprotic solvents such as aliphatic or cyclic ethers, such as 1,2-dimethoxyethane, tetrahydrofuran and dioxane, aliphatic ketones, such as acetone, nitriles, such as acetonitrile, amides, such as dimethylformamide, N-methylpyrrolidone, or sulfoxides, such as dimethyl sulfoxide.
  • bases preferably carbonates, such as potassium hydrogen carbonate, potassium carbonate and sodium carbonate, or alkali metal hydroxides, such as sodium or potassium hydroxide, alkaline earth metal oxides, such as calcium oxide or magnesium oxide, alkali metal alcoholates, such as sodium alcoholate, tertiary amines, such as pyridine derivatives, or ethyldiiso- propylamine.
  • the reaction temperatures are in the range from 0°C to the reflux temperature of the reaction mixture. If desired, the reaction can be accelerated using catalysts, such as crown ethers.
  • the compounds prepared according to the invention can be used, for example, as active ingredients in herbicidal compositions for controlling weeds and grasses in crops of useful plants.
  • Example P1 Preparation of a 5 % Pt-1 Pb-CaCO 3 catalyst:
  • a catalyst prepared in accordance with Example P1 is added to a solution of 10 g of 2-(2-chloro-5-nitro-benzoyloxy)-2-methyl-propionic acid allyl ester in 80 ml of tetrahydrofuran and 20 ml of n-propanol, and the reaction mixture is hydrogenated for 15 hours at a temperature of 140°C and under a hydrogen pressure of
  • Y 3 is the group X 1 -Q-C(O)-X-R 2 or -X-R 2 , wherein X 1' Q, X and R 2 are as defined for formula I.
  • Example P6 Preparation of 2-chloro-5-(4,4,4-trifluoro-3-oxo-butyroylamino)-benzoic acid 1-allyloxy-1-methyl-ethyl ester (Compound No. 2.14):
  • Cyclohexane can be used analogously instead of toluene.
  • Example P7 Preparation of 2-chloro- 5-(4,4,4-trifluoro-3-amino-but-2-enoylamino)- benzoic acid 1-allyloxycarbonyl-1-methyl-ethyl ester (Compound No. 3.14):
  • Example P10 Preparation of 2-chloro-5-(3,6-dihydro-2,6-dioxo-4-trifluoromethyl- 1(2H)-pyrimidinyl)-benzoic acid (1-allyloxycarbonyl-1-methyl)-ethyl ester (Compound No. 6.28):
  • a solution of 1.43 ml of phosgene (20 %) in toluene is added dropwise at a temperature of 40°C to a solution of 1.08 g (2.5 mmol) of 2-chloro-5-(4,4,4-trifluoro-3-amino-but-2- enoylamino)-benzoic acid 1-allyloxycarbonyl-1-methyl-ethyl ester, 0.5 ml of pyridine and 25 mg of 4-dimethylaminopyridine in 40 ml of toluene and the reaction mixture is then stirred for approx. 4.5 hours at the same temperature until the reaction is complete.
  • the desired compound No. 10.2 is also obtained without adding 4-dimethylaminopyridine, for example by reaction in pyridine as solvent at temperatures of from 0° to 100°C, preferably from 35° to 60°C.
  • R 2 , R 3 , R 4 , X, Y, Q, m and n are known or can be obtained in accordance with known methods, either a) by alkylating correspondingly substituted nitrophenols (Y is oxygen), nitrothiophenols (Y is sulfur) or nitroanilines (Y is NR 6 ) of formula VIIc
  • R 3 , R 4 and X are as defined for formula I, with the compound of formula XXII R 2 -L 4 (XXII), wherein R 2 is as defined for formula I and L 4 is a leaving group, in an inert solvent, such as a chlorinated alkane, for example dichloromethane or chloroform, a ketone, for example acetone, a nitrile, for example acetonitrile, N,N-dimethylformamide, N-methyl- pyrrolidone or dimethyl sulf oxide, the reaction temperatures being from -10°C to 150°C, preferably from 0° to 100°C; as alkylating agents of formulae XXI and XXII there may be used, for example, corresponding halides or sulfonyloxy-substituted reagents, such as tosylates or mesylates, where appropriate with the addition of crown ethers or
  • phase-transfer catalysts, or b) the alkylation can be carried out analogously to Org. React. 42, 335 (1992), Editor D.L. Hughes, starting from the corresponding nitrophenols or nitrothiophenols of formula VIIc
  • R 3 and R 4 are as defined for formula I and Y is oxygen or sulfur, by reaction with an alcohol or thiol of formula XX
  • R 3 and R 4 are as defined for formula I and X is oxygen or sulfur, with an alcohol or thiol of formula XX
  • the reactants and reagents can be used in equimolar amounts or in excess (from 1 to 5 equivalents).
  • a solution of 48.4 g of azodicarboxylic acid diethyl ester in 50 ml of dioxane is added dropwise at room temperature to a solution of 35 g of 2-chloro-4-fluoro-5-nitrophenol, 63 g triphenylphosphine and 25.9 g of 2-hydroxy-2-methyl-propionic acid ethyl ester in 300 ml of dioxane, the temperature of the solution rising to 39°C.
  • the reaction mixture is heated and boiled under reflux until the phenol has disappeared (TLC monitoring).
  • the reaction mixture is then concentrated by evaporation, the residue is taken up in a small amount of ethyl acetate and most of the triphenylphosphine oxide formed is precipitated by the addition of hexane and is filtered off.
  • the precipitate is washed thoroughly with hexane/ethyl acetate 1: 1 and the filtrate is washed with water, dried and concentrated by evaporation.
  • the residue is filtered on silica gel using ethyl acetate/hexane 2:8 as eluant. After concentration by evaporation the desired compound is obtained in the form of a yellow-orange oil.
  • Example P15 Preparation of a 5 % Pt-1 % Pb-SiO 2 catalyst
  • the hydrogenation is carried out analogously to Example P3, but with the catalyst prepared in accordance with Example P21.
  • the allyl ester/propyl ester selectivity according to GC (unit area %) is 99 %.
  • the process according to the invention is distinguished by a surprisingly uniform reaction and thus - under mild conditions - leads to high yields of the desired end products. Special mention should be made of the very high yields in process steps a), b) and c).
  • process step b) in particular, the compounds of formula IV wherein R 5 is a strongly electron- attracting substituent, such as CF 3 or CCl 3 , would have been expected to react in different directions resulting in a non-uniform reaction and low yields of the desired end products.

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  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

Composés de la formule (I) dans laquelle les substituants sont tels que définis dans la revendication 1. On obtient ces composés en préparant un composé de formule (IV), en convertissant ce composé en présence d'un agent d'énamination en un composé de formule (III), en faisant réagir ce composé en présence d'une base et d'un solvant interte avec un composé de formule (IIIa) dans laquelle L1 et L2 représentent chacun indépendamment halogène, alcoxy C1-C4, imidazol-1-yle, ou 1,2,4-triazol-1-yle, pour former le composé de formule (II) et en convertissant ce composé, dans un solvant interte, en présence d'une base et avec un composé de formule (IIa) R1-L3, dans laquelle L3 représente halogène ou OSO2OR1, en un composé de formule (I). Ces composés peuvent s'utiliser comme herbicides.
PCT/EP1995/001875 1994-05-27 1995-05-17 Procede de preparation de 3-aryluraciles WO1995032952A1 (fr)

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Cited By (25)

* Cited by examiner, † Cited by third party
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WO1997001541A1 (fr) * 1995-06-29 1997-01-16 Bayer Aktiengesellschaft Cyanophenyluraciles substitues
WO1997029094A1 (fr) * 1996-02-08 1997-08-14 Bayer Aktiengesellschaft Procede de production de cyanophenyluraciles substitues a partir de cyanophenylamides d'acide d'aminoalcene substitues
WO1998027067A1 (fr) * 1996-12-17 1998-06-25 Bayer Aktiengesellschaft Procede pour la preparation de derives de 1-phenyl-uracyle
WO1998027057A2 (fr) * 1996-12-19 1998-06-25 Bayer Aktiengesellschaft Procede pour la preparation d'anilides d'acide trifluoroacetoacetique
WO1999025698A1 (fr) * 1997-11-13 1999-05-27 Bayer Aktiengesellschaft Procede de production d'ar(alk)yluraciles, nouveaux produits intermediaires correspondants et procede de production de ces derniers
US5962741A (en) * 1996-11-19 1999-10-05 Novartis Ag Process for the production of aromatic halogen-amino compounds
US6096924A (en) * 1995-05-19 2000-08-01 Novartis Ag Process for the catalytic hydrogeneration of aromatic nitro compounds
JP2000319264A (ja) * 1998-12-25 2000-11-21 Sumitomo Chem Co Ltd 光学活性ウラシル化合物
US6156700A (en) * 1997-09-17 2000-12-05 American Cyanmid Company 3-(1,2-Benzisothiazol- and isoxazol-5-yl)-2,4(1H,3H)-pyrimidinedione or thione and 3-(1,2-benzisothiazol- and isoxazol-5-yl)-4(3H)-pyrimidinone or thione herbicidal agents
US6258982B1 (en) 1996-09-23 2001-07-10 Novartis Ag Process for the preparation of substituted aromatic amino compounds
JP2001322986A (ja) * 1999-11-15 2001-11-20 Sumitomo Chem Co Ltd ３−フェニルウラシル化合物の製造方法
US6403534B1 (en) 2000-06-28 2002-06-11 Sumitomo Chemical Company, Limited Uracil compounds and use thereof
CN100360509C (zh) * 2005-04-15 2008-01-09 南开大学 用作除草剂的1-嘧啶酮基-4-氯-5-苯甲酸酯类化合物及其制备方法
CN105272973A (zh) * 2014-06-10 2016-01-27 华中师范大学 一种含有苯并噁嗪环的嘧啶二酮类化合物及其应用
WO2018029030A1 (fr) 2016-08-09 2018-02-15 Basf Se Méthode de lutte contre les mauvaises herbes résistant à la ppo
CN110078673A (zh) * 2019-05-31 2019-08-02 深圳大学 一种芳基尿嘧啶类化合物及其制备方法和农药组合物
WO2021063821A1 (fr) 2019-10-01 2021-04-08 Bayer Aktiengesellschaft Dérivés de pyrimidinedione
EP4230620A1 (fr) 2022-02-22 2023-08-23 Bayer Aktiengesellschaft Uracile d'acide n-amino-n´-benzoïque substitués, ainsi que leurs sels et leur utilisation comme herbicides
EP4230621A1 (fr) 2022-02-22 2023-08-23 Bayer AG Uraciles d'acide n-benzoïque substitués, ainsi que leurs sels et leur utilisation comme herbicides
WO2023161172A1 (fr) 2022-02-22 2023-08-31 Bayer Aktiengesellschaft Uraciles d'acide n-benzoïque substitués et leurs sels, et leur utilisation en tant que substances actives herbicides
WO2023247976A1 (fr) 2022-06-24 2023-12-28 Redag Crop Protection Ltd Herbicides deutérés à base d'oxazinones et de 6-(trifluorométhyl)pyrimidine-2,4-diones
WO2024027765A1 (fr) * 2022-08-04 2024-02-08 江苏中旗科技股份有限公司 Procédé de préparation d'un composé uracile contenant un fragment carboxylate
WO2024104956A1 (fr) 2022-11-16 2024-05-23 Bayer Aktiengesellschaft Cycloalkylsulfanylphényluraciles substitués et leurs sels, et leur utilisation comme principes actifs herbicides
WO2024104954A1 (fr) 2022-11-16 2024-05-23 Bayer Aktiengesellschaft Cycloalkyloxyphényluraciles substitues et leurs sels, et leur utilisation comme principes actifs herbicides
WO2024104952A1 (fr) 2022-11-16 2024-05-23 Bayer Aktiengesellschaft Cyclopropyloxyphényluraciles substitués et leurs sels, et leur utilisation comme principes actifs herbicides

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EP0542685A1 (fr) * 1991-11-13 1993-05-19 Ciba-Geigy Ag Dérivés du 3-Aryluracile et leur utilisation dans la lutte contre les mauvaises herbes

Patent Citations (1)

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Publication number Priority date Publication date Assignee Title
EP0542685A1 (fr) * 1991-11-13 1993-05-19 Ciba-Geigy Ag Dérivés du 3-Aryluracile et leur utilisation dans la lutte contre les mauvaises herbes

Cited By (34)

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Publication number Priority date Publication date Assignee Title
US6096924A (en) * 1995-05-19 2000-08-01 Novartis Ag Process for the catalytic hydrogeneration of aromatic nitro compounds
US6495491B1 (en) * 1995-06-29 2002-12-17 Bayer Aktiengesellschaft Substituted cyanophenyl uracils
WO1997001541A1 (fr) * 1995-06-29 1997-01-16 Bayer Aktiengesellschaft Cyanophenyluraciles substitues
AU701851B2 (en) * 1995-06-29 1999-02-04 Bayer Aktiengesellschaft Substituted cyanophenyluracils
JPH11508543A (ja) * 1995-06-29 1999-07-27 バイエル・アクチエンゲゼルシヤフト 置換されたシアノフェニルウラシル類
WO1997029094A1 (fr) * 1996-02-08 1997-08-14 Bayer Aktiengesellschaft Procede de production de cyanophenyluraciles substitues a partir de cyanophenylamides d'acide d'aminoalcene substitues
US6169182B1 (en) 1996-02-08 2001-01-02 Bayer Aktiengesellschaft Process for the preparation of substituted cyanophenyl uracils from substituted aminoalkene acid cyanophenyl amides
US6258982B1 (en) 1996-09-23 2001-07-10 Novartis Ag Process for the preparation of substituted aromatic amino compounds
US5962741A (en) * 1996-11-19 1999-10-05 Novartis Ag Process for the production of aromatic halogen-amino compounds
US6197716B1 (en) 1996-11-19 2001-03-06 Novartis Ag Process for the production of aromatic halogen-amino compounds
WO1998027067A1 (fr) * 1996-12-17 1998-06-25 Bayer Aktiengesellschaft Procede pour la preparation de derives de 1-phenyl-uracyle
CN1100754C (zh) * 1996-12-19 2003-02-05 拜尔公司 三氟乙酰乙酰苯胺的制备方法
WO1998027057A3 (fr) * 1996-12-19 1998-07-23 Bayer Ag Procede pour la preparation d'anilides d'acide trifluoroacetoacetique
WO1998027057A2 (fr) * 1996-12-19 1998-06-25 Bayer Aktiengesellschaft Procede pour la preparation d'anilides d'acide trifluoroacetoacetique
US6156700A (en) * 1997-09-17 2000-12-05 American Cyanmid Company 3-(1,2-Benzisothiazol- and isoxazol-5-yl)-2,4(1H,3H)-pyrimidinedione or thione and 3-(1,2-benzisothiazol- and isoxazol-5-yl)-4(3H)-pyrimidinone or thione herbicidal agents
WO1999025698A1 (fr) * 1997-11-13 1999-05-27 Bayer Aktiengesellschaft Procede de production d'ar(alk)yluraciles, nouveaux produits intermediaires correspondants et procede de production de ces derniers
JP2000319264A (ja) * 1998-12-25 2000-11-21 Sumitomo Chem Co Ltd 光学活性ウラシル化合物
JP2001322986A (ja) * 1999-11-15 2001-11-20 Sumitomo Chem Co Ltd ３−フェニルウラシル化合物の製造方法
US6403534B1 (en) 2000-06-28 2002-06-11 Sumitomo Chemical Company, Limited Uracil compounds and use thereof
CN100360509C (zh) * 2005-04-15 2008-01-09 南开大学 用作除草剂的1-嘧啶酮基-4-氯-5-苯甲酸酯类化合物及其制备方法
CN105272973A (zh) * 2014-06-10 2016-01-27 华中师范大学 一种含有苯并噁嗪环的嘧啶二酮类化合物及其应用
WO2018029030A1 (fr) 2016-08-09 2018-02-15 Basf Se Méthode de lutte contre les mauvaises herbes résistant à la ppo
US10905121B2 (en) 2016-08-09 2021-02-02 Basf Se Method for controlling PPO resistant weeds
CN110078673A (zh) * 2019-05-31 2019-08-02 深圳大学 一种芳基尿嘧啶类化合物及其制备方法和农药组合物
WO2020237823A1 (fr) * 2019-05-31 2020-12-03 深圳大学 Composé d'aryluracile, son procédé de préparation et composition pesticide
WO2021063821A1 (fr) 2019-10-01 2021-04-08 Bayer Aktiengesellschaft Dérivés de pyrimidinedione
EP4230620A1 (fr) 2022-02-22 2023-08-23 Bayer Aktiengesellschaft Uracile d'acide n-amino-n´-benzoïque substitués, ainsi que leurs sels et leur utilisation comme herbicides
EP4230621A1 (fr) 2022-02-22 2023-08-23 Bayer AG Uraciles d'acide n-benzoïque substitués, ainsi que leurs sels et leur utilisation comme herbicides
WO2023161172A1 (fr) 2022-02-22 2023-08-31 Bayer Aktiengesellschaft Uraciles d'acide n-benzoïque substitués et leurs sels, et leur utilisation en tant que substances actives herbicides
WO2023247976A1 (fr) 2022-06-24 2023-12-28 Redag Crop Protection Ltd Herbicides deutérés à base d'oxazinones et de 6-(trifluorométhyl)pyrimidine-2,4-diones
WO2024027765A1 (fr) * 2022-08-04 2024-02-08 江苏中旗科技股份有限公司 Procédé de préparation d'un composé uracile contenant un fragment carboxylate
WO2024104956A1 (fr) 2022-11-16 2024-05-23 Bayer Aktiengesellschaft Cycloalkylsulfanylphényluraciles substitués et leurs sels, et leur utilisation comme principes actifs herbicides
WO2024104954A1 (fr) 2022-11-16 2024-05-23 Bayer Aktiengesellschaft Cycloalkyloxyphényluraciles substitues et leurs sels, et leur utilisation comme principes actifs herbicides
WO2024104952A1 (fr) 2022-11-16 2024-05-23 Bayer Aktiengesellschaft Cyclopropyloxyphényluraciles substitués et leurs sels, et leur utilisation comme principes actifs herbicides

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