Sulfuric Acid → 2-Hydroxyquinoline

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Reaction Steps

Quinolinones (e.g., Structure 35) are prepared from benzoxazines (e.g., Structure 34) by the synthetic route outlined in Scheme VII. Scheme VII begins with an alkylation of a haloketone onto 2-amino-5-nitrophenol (Structure 1) with, for example, 2-bromobutanone, mediated by a base, for example, potassium carbonate, followed by treatment with a reducing agent, for example, sodium cyanoborohydride, in an acid, for example acetic acid, to afford a benzoxazine compound (e.g., Structure 32). The benzoxazine is alkylated at the benzoxazine nitrogen by treatment of a benzoxazine compound (e.g., Structure 32) with an aldehyde, its corresponding hydrate or hemiacetal, with for example, trifluoroacetaldehyde hydrate in the presence of a reducing agent, for example, sodium cyanoborohydride, in an acid, for example trifluoroacetic acid. This procedure affords an alkylated benzoxazine compound (e.g., Structure 33). The nitro derivative of the alkylated benzoxazine compound (Structure 33) is reduced to the corresponding aniline by catalytic hydrogenation or with a reducing agent, for example, zinc and calcium chloride, to afford benzoxazine compound (e.g., Structure 34). Knorr cyclization of an aminobenzoxazine (e.g., Structure 34) by heating with a β-ketoester or corresponding hydrate, with for example, 4,4,4-trifluoroacetoacetate, followed by treatment with an acid, for example, sulfuric acid, affords a quinolinone product (e.g., Structure 35).

Provenance & Evidence