|Budget Amount *help
¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1999 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1998 : ¥1,100,000 (Direct Cost : ¥1,100,000)
1.Synthesis of 2H-1-Benzopyrans by the Reaction of Phenolic Enolates with α, β-unsaturated Compounds
This sequence was successfully applied to the synthesis of an antimicrobial 2, 2-dimethyl-2H-1-benzopyran-6-carboxilic acid, β-tubaic acid (2). Because both conventional and recent methods which were performed in pyridine failed to convert 1 into the desired methyl ester of 2, the present method in aqueous media provides a convenient and one-pot procedure for the preparation of this kind of compound.
Organic syntheses in aqueous media have become one of the main topics of current interest and in general eliminate the constraints of inert atmosphere and anhydrous conditions. Based on the findings that the aldol-type reaction of phenolic enolate of methyl 2, 4-dihydroxybenzoate (1) with aldehydes in methanol was accomplished using alkaline earth metal reagents such as Ca(OH)ィイD22ィエD2, Ba(OH)ィイD22ィエD2, CaCィイD22ィエD2/KOH, or BaClィイD22ィエD2/KOH instead of alkaline metal reagents such as NaOH, KO
H, LiCl/KOH or NaCl/KOH, we have applied the calcium reagent for the reaction of phenolic enolates with α, β-unsaturated aldehydes or ketones in this research. We found that the reaction of 2, 4-dihydroxybenzenecarbonyl compounds with vinyl ketones in HィイD22ィエD24-O/MeOH gave the corresponding 1, 4-adducts and that the reaction with acrolein or methacrolein afforded 3, 4-dihydro-2H-benzopyranes in one pot. In the case of an prenyl-type aldehyde, the nucleophilic reaction proceeded in 1, 2-addition manner, and successive dehydrative cyclization provided a new method for the one-pot formation of 2, 2-disubstituted 2H-benzopyran derivatives. The C-C bond formation was regioselectively performed at the C(3) position of benzoate 1.
2.Synthesis of Benzofurans by the Reaction of Phenolic Enolates with 1, 2-Dicarbonyl Compounds
The treatment of 1 and glyoxal with KOH in water afforded methyl 2, 3-dihydro-2, 3, 4-trihydroxybenzofuran-6-carboxilate in 77% yield, while the reaction carried out in HィイD22ィエD2O/MeOH(1/15) gave methyl 2, 4-dihydroxy-3-(2-hydroxyacetyl)benzoate in one pot.