METHOD FOR PRODUCING SUBSTITUTED ANTHRANILIC ACID DERIVATIVES
The present invention relates to a process for preparing substituted anthranilic acid derivatives of the formula (I) in which R 1 , R 2 , R 3 and R 4 are each as defined in the description, by conversion of compounds of the general formula (IV) in the presence of a palladium catalyst and carbon monoxide. The present invention likewise relates to compounds of the general formula (IV).
1 . Process for preparing a compound of formula (I)
in which
R 1 is optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, or C 6 -C 10 -aryl, or is a hetaryl radical of formula (II)
where
R 8 is C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, which may optionally be mono- or polysubstituted, identically or differently by fluorine or chlorine, or is fluorine, chlorine, cyano, alkylamino, dialkylamino, cycloalkylamino or C 3 -C 6 -trialkylsilyl,
Z is CH or N,
and
Y is hydrogen, fluorine, chlorine, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, or is cyano, alkylamino, dialkylamino, cycloalkylamino, C 3 -C 6 -trialkylsilyl or a radical of formula (III)
where
R 9 is C 1 -C 5 -alkyl which may optionally be mono- or polysubstituted identically or differently by halogen,
R 2 is an OR 5 or NR 6 R 7 radical,
where
R 5 , R 6 and R 7 are each independently hydrogen, C 1 -C 6 -alkyl, or C 6 -C 10 -aryl,
R 3 is hydrogen, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or C 3 -C 6 -cycloalkyl,
R 4 is hydrogen, fluorine, chlorine, cyano, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, C 3 -C 6 -cycloalkylamino, (C 1 -C 4 -alkoxy)imino, (C 1 -C 4 -alkyl)(C 1 -C 4 -alkoxy)imino, SF 5 or C 3 -C 6 -trialkylsilyl,
comprising reacting a substituted anthranilamide derivative of the formula (IV)
in which the R 1 , R 3 and R 4 radicals are each as defined above
and X is chlorine, bromine or iodine,
in the presence of a palladium catalyst and optionally of a phosphine ligand simultaneously with carbon monoxide and a compound of formula (V)
R 5 —OH (V)
in which R 5 is as defined above
or a compound of formula (VI)
HNR 6 R 7 (VI)
in which R 6 and R 7 are each as defined above.
2 . Process according to claim 1 , wherein the compound of formula (IV) is prepared by reacting a Compound of formula (IX)
in which X, R 3 and R 4 are each as defined above
with acids of formula (VIII)
R 1 COOH (VIII)
in which R 1 is as defined above.
3 . Process according to claim 2 , wherein the compound of formula (IV) is prepared in the presence of a condensing agent and of a base.
4 . Process according to claim 1 , wherein the palladium catalyst used is a palladium (II) salt and/or Pd(O) species.
5 . Process according to claim 4 , wherein the palladium catalyst used is bis(dibenzylideneacetone)palladium, tris(dibenzylideneacetone)dipalladium, palladium chloride, palladium bromide and/or palladium acetate.
6 . Process according to claim 1 , wherein the phosphine ligand used is a compound of formula (X)
PR 10 R 11 R 12 (X)
where the R 10 , R 11 and R 12 radicals are each independently hydrogen, linear or branched C 1 -C 8 -alkyl, vinyl, aryl or heteroaryl selected from pyridine, pyrimidine, pyrrole, thiophene and furan, which may in turn be substituted by further substituents from the group of linear or branched C 1 -C 8 -alkyl or C 6 -C 10 -aryl, linear or branched C 1 -C 8 -alkyloxy or C 1 -C 10 -aryloxy, halogenated linear or branched C 1 -C 8 -alkyl or halogenated C 6 -C 10 -aryl, C 6 -C 10 -aryloxycarbonyl, linear or branched C 1 -C 8 -alkylamino, linear or branched C 1 -C 8 -dialkylamino, C 1 -C 8 -arylamino, C 1 -C 8 -diarylamino, hydroxyl, carboxyl, cyano and halogen,
or a chelating biphosphine.
7 . Process according to claim 6 , wherein the chelating biphosphine is one or more selected from 1,2-bis(diphenylphosphino)ethane, 1,2-bis(diphenylphosphino)propane, 1,2-bis(diphenylphosphino)butane, 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl and 1,1′-bis(diphenylphosphino)ferrocene.
8 . Process according to claim 6 , wherein the phosphine ligand used is triphenylphosphine.
9 . Process according to claim 6 , wherein 1-20 molar equivalents of phosphine are used, based on the amount of palladium catalyst used.
10 . Compound of formula (IV)
Where
R 1 is optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, or C 6 -C 10 -aryl, or is a hetaryl radical of formula (II)
where
R 8 is C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, which may optionally be mono- or polysubstituted, identically or differently by fluorine or chlorine, or is fluorine, chlorine, cyano, alkylamino, dialkylamino, cycloalkylamino or C 3 -C 6 -trialkylsilyl,
Z is CH or N,
and
Y is hydrogen, fluorine, chlorine, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, or is cyano, alkylamino, dialkylamino, cycloalkylamino, C 3 -C 6 -trialkylsilyl or a radical of formula (III)
where
R 9 is C 1 -C 5 -alkyl which may optionally be mono- or polysubstituted identically or differently by halogen,
R 2 is an OR 5 or NR 6 R 7 radical,
where
R 5 , R 6 and R 7 are each independently hydrogen, C 1 -C 6 -alkyl, or C 6 -C 10 -aryl,
R 3 is hydrogen, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, C 1 -C 6 -alkoxy or C 3 -C 6 -cycloalkyl,
R 4 is hydrogen, fluorine, chlorine, cyano, optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, C 1 -C 4 -alkylamino, di(C 1 -C 4 -alkyl)amino, C 3 -C 6 -cycloalkylamino, (C 1 -C 4 -alkoxy)imino, (C 1 -C 4 -alkyl)(C 1 -C 4 -alkoxy)imino, SF 5 or C 3 -C 6 -trialkylsilyl.
11 . Compound of formula (IV) according to claim 10 , where
R 1 is optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, or C 6 -C 10 -aryl, or is a hetaryl radical of the general formula (II)
where
R 8 is optionally singly or multiply, identically or differently fluorine- or chlorine-substituted C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, or is fluorine, chlorine, cyano, alkylamino, dialkylamino, cycloalkylamino or C 3 -C 6 -trialkylsilyl,
Z is CH or N, and
Y is hydrogen, fluorine, chlorine, C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 1 -C 6 -fluoro- or -chloroalkyl, C 1 -C 6 -fluoro- or -chlorocycloalkyl, C 1 -C 4 -alkoxy, C 1 -C 4 -fluoro- or -chloroalkoxy, C 1 -C 4 -alkylthio, C 1 -C 4 -alkylsulphinyl, C 1 -C 4 -alkylsulphonyl, C 1 -C 4 -fluoro- or -chloroalkylthio, C 1 -C 4 -fluoro- or -chloroalkylsulphinyl, C 1 -C 4 -fluoro- or -chloroalkylsulphonyl, cyano, alkylamino, dialkylamino, cycloalkylamino, C 3 -C 6 -trialkylsilyl or a radical of the general formula (III)
in which
R 9 is C 1 -C 5 -alkyl which may be mono- or polysubstituted identically or differently by halogen,
R 3 is methyl,
R 3 is likewise chlorine,
R 4 is chlorine or cyano,
and
X is bromine or iodine.
12 . Compound of formula (IV) according to claim 10 , where
R 1 is a hetaryl radical of the general formula (II)
where
R 8 is fluorine or chlorine,
Z is N,
and
Y is hydrogen, fluorine, chlorine or a radical of the general formula (III)
where
R 9 is CF 3 or C 2 F 5 ,
R 3 is methyl,
R 4 is chlorine or cyano,
and
X is bromine.