Method for producing N-sulfonyl-substituted oxindoles
View Patent ↗Process for the selective N-sulfonylation of oxindoles, in particular process for the N-sulfonylation of 3-triazinyloxindoles, and also N-sulfonyl-substituted 3-triazinyloxindoles and the use of N-sulfonyl-substituted oxindoles and of N-sulfonyl-substituted 3-triazinyloxindoles as intermediates for the synthesis of fine chemicals and of active ingredients in the field of pharmacy and agriculture, and also the use of these compounds as active ingredients in the field of agriculture.
1. A process for preparing an N-sulfonyl-substituted oxindole of formula (3)
in which
R 1a to R 1d , independently of one another, are selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, and also from
(C 1 -C 6 )-alkyl, where the alkyl radical is branched or unbranched and is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl,
(C 3 -C 7 )-cycloalkyl, where the cycloalkyl radical is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 3 -C 7 )-cycloalkyl or (C 1 -C 4 )-alkoxy,
(C 1 -C 6 )-alkoxy, where the alkoxy radical is branched or unbranched and is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl,
(C 3 -C 7 )-cycloalkoxy, where the cycloalkoxy radical is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy,
(C 1 -C 6 )-alkylthio, where the alkylthio radical is branched or unbranched and is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C1-C4)-alkyl or (C1-C4)-alkoxy,
(C 3 -C 7 )-cycloalkylthio, where the cycloalkylthio radical is unsubstituted or is substituted by at least one substituents selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy, and phenyl or 1-naphthyl or 2-naphthyl or a five- or six-membered heteroaromatic ring comprising from 1 to 2 heteroatoms, where said heteroatoms are selected, independently of one another, from the group consisting of O or N and where the aryl or heteroaryl radical is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, bromine, iodine, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl or (C 1 -C 4 )-alkylthio, and
R 2 is
(C 1 -C 6 )-alkyl, where the alkyl radical is unsubstituted or is completely or partially substituted with fluorine, or
(C 3 -C 7 )-cycloalkyl, where the cycloalkyl radical is unsubstituted or is completely or partially substituted with fluorine,
R 3 is
hydrogen or
(C 1 -C 6 )-alkyl, where the alkyl radical is branched or unbranched and is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl,
(C 1 -C 6 )-alkylthio, where the alkylthio radical is unsubstituted or is substituted by at least one substituents selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy,
and
Q is
a six-membered heteroaromatic ring comprising from 1 to 3 nitrogen atoms, where the heteroaromatic ring is unsubstituted or is substituted by at least one substituent selected from the group consisting of (C 1 -C 4 )-alkyl, (C1-C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl or (C 3 -C 7 )-cycloalkoxy or (C 1 -C 4 )-alkylthio,
said process comprising reacting of an oxindole compound of formula
in which
R 1a to R 1d , and R 3 and Q are as defined in formula (3),
in a solvent with a sulfonyl compound (2)
in which
R 2 is as defined in formula (3), and
X, as leaving group, is
fluorine, chlorine, or bromine,
where said reaction is carried out in the presence of an imidazole base substituted in the 1 position, or
a base mixture which comprises at least one imidazole base substituted in the 1 position,
wherein the N-sulfonyl-substituted oxindole of formula (3) is prepared from an imidazole base substituted in the 1 position.
2. A compound of formula (3) or salt thereof
in which
R 1a to R 1d , independently of one another, are selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, and also from
(C 1 -C 6 )-alkyl, where the alkyl radical is branched or unbranched and is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl,
(C 3 -C 7 )-cycloalkyl, where the cycloalkyl radical is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 3 -C 7 )-cycloalkyl or (C 1 -C 4 )-alkoxy,
(C 1 -C 6 )-alkoxy, where the alkoxy radical is branched or unbranched and is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl,
(C 3 -C 7 )-cycloalkoxy, where the cycloalkoxy radical is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy,
(C 1 -C 6 )-alkylthio, where the alkylthio radical is branched or unbranched and is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C1-C4)-alkyl or (C1-C4)-alkoxy,
(C 3 -C 7 )-cycloalkylthio, where the cycloalkylthio radical is unsubstituted or is substituted by at least one substituents selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy, and phenyl or 1-naphthyl or 2-naphthyl or a five- or six-membered heteroaromatic ring comprising from 1 to 2 heteroatoms, where said heteroatoms are selected, independently of one another, from the group consisting of O or N and where the aryl or heteroaryl radical is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, bromine, iodine, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl or (C 1 -C 4 )-alkylthio, and
R 2 is
(C 1 -C 6 )-alkyl, where the alkyl radical is unsubstituted or is completely or partially substituted with fluorine, or
(C 3 -C 7 )-cycloalkyl, where the cycloalkyl radical is unsubstituted or is completely or partially substituted with fluorine,
R 3 is
hydrogen or
(C 1 -C 6 )-alkyl, where the alkyl radical is branched or unbranched and is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl,
(C 1 -C 6 )-alkylthio, where the alkylthio radical is unsubstituted or is substituted by at least one substituents selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy,
and
Q is
a six-membered heteroaromatic ring comprising from 1 to 3 nitrogen atoms, where the heteroaromatic ring is unsubstituted or is substituted by at least one substituent selected from the group consisting of (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl or (C 3 -C 7 )-cycloalkoxy or (C 1 -C 4 )-alkylthio,
prepared by a process comprising reacting of an oxindole compound of formula
in which
R 1a to R 1d , and R 3 and Q are as defined in formula (3),
in a solvent with a sulfonyl compound (2)
in which
R 2 is as defined in formula (3), and
X, as leaving group, is
fluorine, chlorine, or bromine,
where said reaction is carried out in the presence of an imidazole base substituted in the 1 position, or
a base mixture which comprises at least one imidazole base substituted in the 1 position.
3. A method for producing an intermediate capable of being used for producing an active ingredient for agriculture, the method comprising oxidative ring-opening with hydrogen peroxide or potassium permanganate of the oxindole group of a compound of formula (3) or salt thereof
in which
R 1a to R 1d , independently of one another, are selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, and also from
(C 1 -C 6 )-alkyl, where the alkyl radical is branched or unbranched and is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl,
(C 3 -C 7 )-cycloalkyl, where the cycloalkyl radical is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 3 -C 7 )-cycloalkyl or (C 1 -C 4 )-alkoxy,
(C 1 -C 6 )-alkoxy, where the alkoxy radical is branched or unbranched and is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl,
(C 3 -C 7 )-cycloalkoxy, where the cycloalkoxy radical is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy,
(C 1 -C 6 )-alkylthio, where the alkylthio radical is branched or unbranched and is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C1-C4)-alkyl or (C1-C4)-alkoxy,
(C 3 -C 7 )-cycloalkylthio, where the cycloalkylthio radical is unsubstituted or is substituted by at least one substituents selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy, and phenyl or 1-naphthyl or 2-naphthyl or a five- or six-membered heteroaromatic ring comprising from 1 to 2 heteroatoms, where said heteroatoms are selected, independently of one another, from the group consisting of O or N and where the aryl or heteroaryl radical is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, bromine, iodine, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl or (C 1 -C 4 )-alkylthio, and
R 2 is
(C 1 -C 6 )-alkyl, where the alkyl radical is unsubstituted or is completely or partially substituted with fluorine, or
(C 3 -C 7 )-cycloalkyl, where the cycloalkyl radical is unsubstituted or is completely or partially substituted with fluorine,
R 3 is
hydrogen
and
Q is
a six-membered heteroaromatic ring comprising from 1 to 3 nitrogen atoms, where the heteroaromatic ring is unsubstituted or is substituted by at least one substituent selected from the group consisting of (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl or (C 3 -C 7 )-cycloalkoxy or (C 1 -C 4 )-alkylthio.
4. A method for producing an active ingredient for agriculture, the method comprising oxidative ring-opening with hydrogen peroxide or potassium permanganate of the oxindole group of a compound of formula (3-1) or (3-1a)
or a salt thereof (3-1a)
in which, in each case,
R 1a to R 1d , independently of one another, are selected from the group consisting of hydrogen, fluorine, chlorine, bromine, iodine, and also of
(C 1 -C 6 )-alkyl, where the alkyl radical is branched or unbranched and is unsubstituted or is substituted by at least one or more substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl,
(C 3 -C 7 )-cycloalkyl, where the cycloalkyl radical is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 3 -C 7 )-cycloalkyl or (C 1 -C 4 )-alkoxy,
(C 1 -C 6 )-alkoxy, where the alkoxy radical is branched or unbranched and is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )—
cycloalkyl,
(C 3 -C 7 )-cycloalkoxy, where the cycloalkoxy radical is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy,
(C 1 -C 6 )-alkylthio, where the alkylthio radical is branched or unbranched and is unsubstituted or is substituted by at least one or more substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 1 -C 4 )—
alkoxy,
(C 3 -C 7 )-cycloalkylthio, where the cycloalkylthio radical is unsubstituted or is substituted by at least one or more substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkyl or (C 1 -C 4 )-alkoxy, and
phenyl or 1-naphthyl or 2-naphthyl or a five- or six-membered heteroaromatic ring comprising from 1 to 2 heteroatoms, where said heteroatoms,
independently of one another, are selected from the group consisting of O or N, and where the aryl or heteroaryl radical is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, bromine, iodine, (C 1 -C 4 )-alkyl, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl or (C 1 -C 4 )-alkylthio, and
R 2 is
methyl, where the methyl is completely or partially substituted with fluorine, or (C 3 -C 7 )-cycloalkyl, where the cycloalkyl radical is completely or partially substituted with fluorine,
R3 is hydrogen,
R 4 and R 5 , independently of one another, are in each case
hydrogen,
(C 1 -C 6 )-alkyl, where the alkyl radical is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl,
(C 1 -C 6 )-alkoxy, where the alkoxy radical is branched or unbranched and is unsubstituted or is substituted by at least one substituent selected from the group consisting of fluorine, chlorine, (C 1 -C 4 )-alkoxy or (C 3 -C 7 )-cycloalkyl,
where, in the salt of formula (3-1a), M is Li, Na, K, Cs, Ba, Mg, Ca, Zn or N(R c ) 4 , where R c ═H or C 1 -C 6 alkyl, and where the number of counterions M + is determined by a particular charge, such that an overall neutral compound of the formula (3-1a) is formed.