A method for the sequential oxidation of substituted-8-hydroxy-quinolines to produce substituted-pyridine-2,3-dicarboxylic acids

Claim 1

A method for the preparation of pyridine-­2,3-dicarboxylic acids of formula I wherein X is hydrogen, halogen, or methyl, with the proviso that when Y and Z are taken together to form a ring, and YZ is represented by the struc­ture: -(CH₂) n -, where n is 3 or 4, X is hydrogen; Y and Z each represent members selected from the group consisting of hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ hydroxyalkyl, C₁-C₆ haloalkyl, C₁-C₆ aminoalkyl, C₁-C₆ sulfonylalkyl, nitro, hydroxy, formyl, carboxy, acyl, amido, amino, C₁-C₄ alkylamino, diloweralkylamino, C₁-C₄ alkylsulfonyl, sulfonamido, or phenyl option­ally substituted with one C₁-C₄ alkyl group, C₁-C₄ alkylsulfonyl group, halogen, hydroxy, or trifluoromethyl group, and when taken together, Y and Z may form a ring in which YZ are represented by the structure: -(CH₂) n -, where n is an integer selected from 3 or 4, provided that X is hydrogen; or where L, M, Q, and R₁ each repre­sent members selected from the group con­sisting of hydroxy, halogen, C₁-C₄ alkyl, C₁-C₄ alkylsulfonyl, C₁-C₄ haloalkylamino, C₁-C₄ alkylamino, diloweralkylamino, and trifluoromethyl, with the proviso that only one of L, M, Q or R₁ may represent a sub­stituent other than hydrogen, halogen, or C₁-C₄ alkyl, characterized by reacting an 8-hydroxyquinoline compound of formula II wherein X, Y, and Z are as described for formula I above with from about 7 to 14 molar equivalents of hydrogen peroxide as a 30%-50% aqueous solution in the presence of 5.5 molar equivalents of aqueous base at 60-100°C and holding for one hour followed by cooling said reaction mixture to 25-90°C, adding mineral acid to obtain a pH of about 8-13, then adding about 1.0-2.0 molar equivalents of hypochlorite as a 5%-30% aqueous solution or generated in situ by the addition of chlorine gas and after one to two hours at 65-75°C, the product dicarboxylic acid may be isolated.

Claim 2

A method for the preparation of pyridine-­2,3-dicarboxylic acids of formula I wherein X is hydrogen, halogen, or methyl, with the proviso that when Y and Z are taken together to form a ring, and YZ is represented by the struc­ture: -(CH₂) n -, where n is 3 or 4, X is hydrogen; Y and Z each represent members selected from the group consisting of hydrogen, halogen, C₁-C₆ alkyl, C₁-C₆ hydroxyalkyl, C₁-C₆ haloalkyl, C₁-C₆ aminoalkyl, C₁-C₆ sulfonylalkyl, nitro, hydroxy, formyl, carboxy, acyl, amido, amino, C₁-C₄ alkylamino, diloweralkylamino, C₁-C₄ alkylsulfonyl, sulfonamido, or phenyl option­ally substituted with one C₁-C₄ alkyl group, C₁-C₄ alkylsulfonyl group, halogen, hydroxy, or trifluoromethyl group, and when taken together, Y and Z may form a ring in which YZ are represented by the structure: -(CH₂) n -, where n is an integer selected from 3 or 4, provided that X is hydrogen; or where L, M, Q, and R₁ each repre­sent members selected from the group con­sisting of hydroxy, halogen, C₁-C₄ alkyl, C₁-C₄ alkylsulfonyl, C₁-C₄ haloalkylamino, C₁-C₄ alkylamino, diloweralkylamino, and trifluoromethyl, with the proviso that only one of L, M, Q or R₁ may represent a sub­stituent other than hydrogen, halogen, or C₁-C₄ alkyl, characterized by reacting an 8-hydroxyquinoline compound of formula II wherein X, Y, and Z are as described for formula I above with from about 7 to 14 molar equivalents of hydrogen peroxide as a 30%-50% aqueous solution in the presence of 5.5 molar equivalents of aqueous base at 60-100°C and holding for one hour followed by cooling said reaction mixture to 25-90°C, adding mineral acid to obtain a pH of about 8-13, then adding about 1.0-2.0 molar equivalents of hypochlorite as a 5%-30% aqueous solution or generated in situ by the addition of chlorine gas and after one to two hours at 65-75°C, the product dicarboxylic acid may be isolated.