Organic compounds -- part of the class 532-570 series – Organic compounds – Nitrogen attached directly or indirectly to the purine ring...
Reexamination Certificate
2000-01-18
2001-10-30
Shah, Mukund J. (Department: 1624)
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitrogen attached directly or indirectly to the purine ring...
C544S319000, C546S293000, C548S225000, C548S228000, C548S229000, C548S243000, C548S366100, C549S065000, C549S479000
Reexamination Certificate
active
06310206
ABSTRACT:
TECHNICAL FIELD OF THE INVENTION
The invention relates to a novel process for preparing N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides, which are known as intermediates in the preparation of herbicides, to novel N-(2-cyano-4,5-difluoro-phenyl)-sulphonamides and N-(2-cyano-4,5-difluoro-phenyl)-sulphonimides as intermediates for this process and to processes for their preparation.
BACKGROUND OF THE INVENTION
It is known that certain N-(5-amino-2-cyano-4-fluoro-phenyl)-alkanesulphonamides, such as, for example, N-(5-amino-2-cyano-4-fluoro-phenyl)-methanesulphonamide, are obtained when corresponding halogenated benzene derivatives, such as, for example, 1-amino-4-cyano-2,5-difluoro-benzene, are heated with alkanesulphonamides, such as, for example, methanesulphonamide, in the presence of an acid binder, such as, for example, potassium carbonate, and in the presence of a diluent, such as, for example, N-methyl-pyrrolidone (see EP-A-648772). However, this process affords the desired products in unsatisfactory yields. Accordingly, there is a need for a more favourable preparation process for N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides.
DETAILED DESCRIPTION OF THE INVENTION
It has now been found that N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides of the general formula (I)
in which
R represents in each case optionally substituted alkyl, alkenyl, alkinyl, cyclo-alkyl, cycloalkylalkyl, aryl, arylalkyl, heterocyclyl or heterocyclylalkyl
are obtained in high yields and in very good quality when, in a first step, 2-amino-4,5-difluoro-benzonitrile of the formula (II)
is reacted with sulphonyl halides of the general formula (III)
X—SO
2
—R (III)
in which
R is as defined above and
X represents halogen
in the presence of an acid acceptor and in the presence of a diluent at temperatures between 0° C. and 150° C.
and the resulting N-(2-cyano-4,5-difluoro-phenyl)-sulphonamide intermediates of the general formula (IV) and/or N-(2-cyano-4,5-difluoro-phenyl)-sulphonimide intermediates of the general formula (V)
in which
R is as defined above
are reacted as pure substances or as mixtures in a second step with ammonia in the presence of a diluent at temperatures between 100° and 200° C.
Surprisingly, the N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides of the general formula (I) can be obtained by the process according to the invention in a relatively simple manner in high yields and in very good quality, and a pure end product can be prepared via a mixture of intermediates. The intermediates of the formulae (IV) and (V) can be obtained as mixtures in virtually quantitative yield.
The main advantage of the process according to the invention is the fact that the use of relatively expensive 2,4,5-trifluoro-benzonitrile can be dispensed with, and the problematic exchange of a fluorine substituent for a sulphonylamino group is not necessary.
The compound 2-amino-4,5-difluoro-benzonitrile of the formula (II) to be used as starting material has not yet been disclosed in the literature; as a novel substance, it also forms part of the subject-matter of the present invention.
The novel compound of the formula (II) is obtained when 4,5-difluoro-2-nitro-benzonitrile of the formula (VI)
is reacted with a reducing agent which is customary for converting aromatic nitro compounds into the corresponding amino compounds, such as, for example, (a) hydrogen in the presence of a catalyst such as, for example, platinum or palladium (where the two last-mentioned compounds are, if appropriate, “poisoned” and supported on a carrier, such as, for example, activated carbon or barium sulphate), in the presence of a diluent, such as, for example, tetrahydrofuran or dioxane, or (b) metals or metal salts, such as, for example, tin, tin(II) chloride, iron (powder) in the presence of an acid, such as, for example, hydrochloric acid or acetic acid, and, if appropriate, additionally in the presence of a diluent, such as, for example, methanol or ethanol, at temperatures between 0° C. and 150° C., preferably between 10° C. and 100° C. (cf. the Preparation Examples).
The intermediates of the formulae (IV) and (V) are not yet known from the literature; as novel substances, they also form part of the subject-matter of the present invention.
The 4,5-difluoro-2-nitro-benzonitrile of the formula (VI) required as precursor is already known (see JP 07070041 - cited in Chem. Abstracts 123:111678). According to the patent literature cited, 4,5-difluoro-2-nitro-benzonitrile can be prepared by reaction of 2-bromo-4,5-difluoro-nitrobenzene with copper(I) cyanide in N,N-dimethyl-formamide.
However, the compound of the formula (VI) is also obtained when 3,4-difluoro-benzonitrile is reacted with nitric acid, if appropriate in the presence of sulphuric acid, at temperatures between −10° C. and +30° C. (cf. the Preparation Examples).
Surprisingly, this nitration proceeds in a very uniform manner (regioselectively), and hydrolysis of the cyano group, which is to be expected under the nitration conditions, only occurs to a very low extent.
The formula (III) provides a general definition of the sulphonyl halides further to be used as starting materials in the process according to the invention for preparing N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides of the general formula (I).
Preferred meanings in the formulae (I), (III), (IV) and (V) are:
R represents in each case optionally halogen-substituted alkyl, alkenyl or alkinyl having in each case up to 6 carbon atoms, represents in each case optionally halogen- or C
1
-C
4
-alkyl-substituted cycloalkyl or cycloalkylalkyl having in each case 3 to 6 carbon atoms in the cycloalkyl group and, if appropriate, 1 to 4 carbon atoms in the alkyl moiety, represents in each case optionally nitro-, cyano-, halogen-, C
1
-C
4
-alkyl-, C
1
-C
4
-halogenoalkyl-, C
1
-C
4
-alkoxy-, C
1
-C
4
-halogenoalkoxy- or C
1
-C
4
-alkoxy-carbonyl-substituted aryl or arylalkyl having 6 or 10 carbon atoms in the aryl group and, if appropriate, 1 to 4 carbon atoms in the alkyl moiety, or represents in each case optionally cyano-, halogen-, C
1
-C
4
-alkyl-, C
1
-C
4
-halogenoalkyl-. C
1
-C
4
-alkoxy- or C
1
-C
4
-halogenoalkoxy-substituted heterocyclyl or heterocyclylalkyl having in each case 3 to 5 carbon atoms and 1 or 2 nitrogen atoms and/or one oxygen or sulphur atom in the heterocyclyl group and, if appropriate, 1 to 4 carbon atoms in the alkyl moiety, and
x represents fluorine, chlorine or bromine.
Particularly preferred meanings in the above formulae are:
R represents in each case optionally fluorine- or chlorine-substituted methyl, ethyl, n- or i -propyl, n-, i-, s- or t-butyl, ethenyl, propenyl, butenyl, ethinyl, propinyl or butinyl, represents in each case optionally fluorine-, chlorine-, methyl- or ethyl-substituted cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl or cyclohexyl-methyl, represents in each case optionally nitro-, cyano-, fluorine-, chlorine-, bromine-, methyl-, ethyl-, n- or i-propyl-, n-, i-, s- or t-butyl-, tri- fluoromethyl-, methoxy-, ethoxy-, n- or i-propoxy-, n-, i-, s- or t-butoxy-, difluoromethoxy-, trifluoromethoxy-, methoxycarbonyl-, ethoxycarbonyl-, n- or i-propoxycarbonyl-substituted phenyl or benzyl, or represents in each case optionally cyano-, fluorine-, chlorine-, bromine-, methyl-, ethyl-, n- or i-propyl-, n-, i-, s- or t-butyl-, trifluoromethyl-, methoxy-, ethoxy-, n- or i-propoxy-, n-, i-, s- or t-butoxy-, difluoromethoxy- or trifluoromethoxy-sub-situated heterocyclyl from the group consisting of furyl, thienyl, oxazolyl, isoxazolyl, pyrazolyl, pyridinyl and pyrimidinyl, and
x represents chlorine.
The starting materials of the formula (III) are known chemicals for synthesis.
The first step of the process according to the invention for preparing N-(5-amino-2-cyano-4-fluoro-phenyl)-sulphonamides of the general formula (I) is carried out using an acid acceptor. Suitable acid acceptors are, in general, the customary inorganic or organic bases or acid acceptors. These preferably include a
Drewes Mark Wilhelm
Erdman David
Hupperts Achim
Lantzsch Reinhard
Bayer Aktiengesellschaft
Gil Joseph C.
McKenzie Thomas C
Shah Mukund J.
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