Organic compounds -- part of the class 532-570 series – Organic compounds – Amino nitrogen containing
Reexamination Certificate
2002-06-11
2003-02-04
O'Sullivan, Peter (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Amino nitrogen containing
C548S533000, C548S535000, C548S953000, C560S157000, C560S160000, C562S574000, C564S355000
Reexamination Certificate
active
06515179
ABSTRACT:
TECHNICAL FIELD
The present invention relates to an improved chemical method for converting a 2- or 4-nitrobenzenesulfonamide to a corresponding amine. The nitrobenzenesulfonamide is a compound in which an amino group is protected with a nitrobenzenesulfonyl group which is a protective group, and is widely used. The method of the present invention is extremely useful as a method for removing the above protective group in producing an optically active amine useful as an intermediate of a pharmaceutical or an agricultural chemical, or an intermediate of a physiologically active substance or the like.
BACKGROUND ART
It is known that a 2- or 4-nitrobenzenesulfonyl group is useful as an amino protective group for an optically active amine or an amino acid which is important as an intermediate of a pharmaceutical or a physiologically active substance, and the group is often used in the course of synthesis of such a compound. As methods for removing the nitrobenzenesulfonyl group, only methods as described below are known in which a thiolate ion is allowed to act in the coexistence of a base:
(1) A method using potassium carbonate as a base, thiophenol as a thiol, and N,N-dimethylformamide as a solvent, which is the most general method (
Tetrahedron Lett.,
36: 6373 (1995);
J. Am. Chem. Soc.,
121: 6761 (1999);
Angew. Chem. Int. Ed.,
39: 1323 (2000);
J. Am. Chem. Soc.,
122: 976 (2000); and the like);
(2) A method using potassium carbonate as a base, thiophenol as a thiol, and acetonitrile as a solvent (
Tetrahedron Lett.,
38: 5253 (1997));
(3) A method using cesium carbonate as a base, thiophenol as a thiol, and N,N-dimethylformamide as a solvent (
J. Org. Chem.,
62: 1586 (1997));
(4) A method using diisopropylethylamine as a base, thiophenol as a thiol, and N,N-dimethylformamide as a solvent (
Tetrahedron Lett.,
39: 3889 (1998));
(5) A method using n-propylamine as a base, thiophenol as a thiol, and dimethoxyethane as a solvent (JP-A-11-171860);
(6) A method using lithium hydroxide as a base, thioglycolic acid as a thiol, and N,N-dimethylformamide as a solvent (
Tetrahedron Lett.,
36: 6373 (1995)); and
(7) A method using 1,8-diazabicyclo[5.4.0]-7-undecene as a base, mercaptoethanol as a thiol, and N,N-dimethylformamide as a solvent (
J. Am. Chem. Soc.,
119: 2301 (1997)).
DISCLOSURE OF THE INVENTION
However, in any of the above methods, the ill-smelling thiol compounds have to be used. For industrially carrying out the above-described methods, there is the serious problem that special equipment in which consideration for the environment such as smell-removing measures is taken is required, or that treatment for making the thiol compounds odorless after reaction, which are ordinarily used in excess, becomes necessary. Accordingly, the development of a method for removing the 2- or 4-nitrobenzenesulfonyl group has been desired which can avoid the use of a thiol, is simple, has general-purpose properties, and is more industrially advantageous.
In view of the above-described state, the present inventor has made intensive studies for solving such a problem. As a result, the inventor has discovered that the nitrobenzenesulfonyl group bonded to an amino group can be easily removed to convert the nitrobenzenesulfonamide to a corresponding amine by allowing an alkali metal alkoxide to act on a 2- or 4-nitrobenzenesulfonamide, thus completing the present invention.
That is to say, the present invention relates to a method for removing a nitrobenzenesulfonyl group from a nitrobenzenesulfonamide and a method for producing an amine derivative using this method, having the following constitutions:
1. A method for removing a nitrobenzenesulfonyl group from a compound represented by the following formula (1), which comprising bringing the compound represented by formula (1) into contact with an alkali metal alkoxide:
wherein R
1
and R
2
, which are the same or different, each represents a hydrogen atom or an aliphatic or alicyclic hydrocarbon group which may be substituted, or an atomic group in which R
1
and R
2
combine with each other at their ends together with an adjacent nitrogen atom to form a cyclic amine which may be substituted; and Ns represents a 2-nitrobenzenesulfonyl group or a 4-nitrobenzenesulfonyl group.
2. The method according to the above item 1, wherein the compound represented by formula (1) is a nitrobenzenesulfonamide of an &agr;-amino acid derivative or a &bgr;-amino acid derivative.
3. The method according to the above item 1, wherein the compound represented by formula (1) is a nitrobenzenesulfonamide of an amino alcohol derivative.
4. The method according to any one of the above items 1 to 3, wherein the alkali metal alkoxide is an alkali metal methoxide.
5. The method according to any one of the above items 1 to 4, wherein the alkali metal in the alkali metal alkoxide is lithium or sodium.
6. A method for producing an amine derivative represented by the following formula (2), which comprises converting the compound represented by formula (1) to a compound in which the nitrobenzenesulfonyl group is removed according to the method according to any one of the above items 1 to 5, and allowing the compound without isolation to react with an activated substituted oxycarbonyl compound or an activated acyl compound:
wherein R
1
and R
2
are the same as described above, and R
3
represents a substituted oxycarbonyl group or an acyl group.
BEST MODE FOR CARRYING OUT THE INVENTION
The present invention is described in detail below.
First, the 2- or 4-nitrobenzenesulfonamide used as a starting material in the present invention is represented by the following formula (1):
wherein R
1
and R
2
, which are the same or different, each represents a hydrogen atom or an aliphatic or alicyclic hydrocarbon group which may be substituted, or an atomic group in which R
1
and R
2
combine with each other at their ends together with an adjacent nitrogen atom to form a cyclic amine which may be substituted; and Ns represents a 2-nitrobenzenesulfonyl group or a 4-nitrobenzenesulfonyl group.
The above-described compound (hereinafter referred to as compound (1)) is usually synthesized by allowing a corresponding amine with a 2- or 4-nitrobenzenesulfonyl halide in a solvent, in the coexistence of a base. As the 2- or 4-nitrobenzenesulfonyl halide, a chloride thereof is suitably used.
Furthermore, as the above-described base, either an organic base or an inorganic base can be used. As the organic base, generally, a tertiary amine which does not consume the 2- or 4-nitrobenzenesulfonyl halide by reaction with the reagent is suitably used. Examples include trimethylamine, triethyl amine, tri-n-propyl amine, tri-n-butyl amine, disopropylethylamine, N,N,N′,N′-tetramethylethylenediamine, N,N,N′,N′-tetramethyl-1,3-propanediamine, N-methylmorpholine, N,N′-dimethylpiperazine, 1,4-diazabicyclo[2.2.2]octane, 1,5-diazabicyclo[4.3.0]-5-nonene, 1,8-diazabicyclo[5.4.0]-7-undecene and the like. Heterocyclic aromatic amines such as pyridine, 4-dimethylaminopyridine, collidine, lutidine and the like are also available.
Examples of the inorganic base include alkali metal hydroxides such as lithium hydroxide, sodium hydroxide, potassium hydroxide and the like, alkaline earth metal hydroxides such as magnesium hydroxide, calcium hydroxide, barium hydroxide and the like, alkaline metal carbonates such as lithium carbonate, sodium carbonate, potassium carbonate, cesium carbonate and the like, and quaternary ammonium hydroxides such as tetrabutylammonium hydroxide, tetraethylammonium hydroxide, tetramethylammonium hydroxide and the like.
Although there is no particular limitation on the solvent used in the reaction, suitably used are organic solvents, water, mixed solvents of hydrophilic organic solvents and water, and the like, which are usually often employed. Examples of these solvents include methylene chloride, chloroform, N,N-dimethylformamide, acetonitrile, dioxane, tetrahydrofuran, dimethoxyethane, tert-butyl alcohol, water-dioxan
Kaneka Corporation
O'Sullivan Peter
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