Synthesis and reactions of halo-, nitro-, and arylazo-substituted 3-acetyltropolones. Formation of heterocycle-fused troponoid compounds

3-Cinnamoyltropolone and 3-(3-methoxycinnamoyl)tropolone were oxidized with 2,3-dichloro-5,6-dicyanobenzoquinone to give 2-phenyl- and 2-(3-methoxyphenyl)-4,9-dihydrocyclohepta[b]pyran-4,9-diones, while 2′-and/or 4′-methoxy-substituted 3-cinnamoyltropolones gave 2-arylmethylene-2H-3,8-dihydrocyclohepta[b]furan-3,8-diones.

Cyclodehydrogenation of 3-Cinnamoyltropolones with 2,3-Dichloro-5,6-dicyanobenzoquinone

Reactions of 3-acetyltropolone and its methyl ethers with hydroxylamine. Formation of 8H-cyclohept[d]isoxazol-8-one and 8H-cyclohept[c]isoxazol-8-one

A convenient method to obtain a series of bromo-substituted flavone-like troponoid compounds 6,8-dibromo-2-arylcyclohepta[b]pyran-4,9-diones 3a–3s by oxidation cyclization of the readily available intermediates 3-cinnamoyl-5,7-dibromotropolones 2a–2s using I2/DMSO/H2SO4 system was realized. Compounds 2a–2s were obtained from the aldol reaction of 3-acetyl-5,7-dibromotropolone 1 with various benzaldehydes. Compounds 2a–2s and 3a–3s are novel and their structures were supported by IR, 1H NMR, MS and elemental analyses.

Synthesis of Novel Bromo-substituted Flavone-like Troponoid Compounds from Oxidation Cyclization of 3-Cinnamoyl-5,7-dibromotropolones Using I2/DMSO/H2SO4 System

A facile and clean synthesis of novel 2-tropolonyl substituted quinoline-4-carboxylic acids via Pfitzinger reaction of 3-acetyltropolone or 3-acetyl-5-bromotropolone with different isatins in water was described. It was the first time that the Pfitzinger reaction was applied to the troponoid field. The structures of all the synthesized compounds were characterized by elemental analysis and spectral data.

First synthesis of 2-tropolonylquinoline-4-carboxylic acid derivatives via Pfitzinger reaction in water

3-Acetyltropolone (1) was synthesized from 3-isopropenyltropolone by treatment with sodium azide in concentrated sulfuric acid. Methylation of 1 by diazomethane gave two isomers, 3-acetyl-2-methoxytropone (2a) and 2-acetyl-7-methoxytropone (2b). 1, 2a, and 2b reacted with hydrazine to give some 1,8-dihydrocycloheptapyrazol-8-one derivatives.

Reactions of 3-acetyltropolone and its methyl ethers with hydrazine.

Alkaline condensation of 3-acetyltropolone (1) with benzaldehydes gave 3-cinnamoyltropolones (2 a-d), which were cyclized with concentrated orthophosphoric acid to afford 2-aryl-2, 3, 4, 9-tetra-hydrocyclohepta [b] pyran-4, 9-diones (3a-d) and oxidized with selenium dioxide to give 2-aryl-4, 9- dihydrocyclohepta [b] pyran-4, 9-diones (4a-d).

Synthesis and Cyclization of 3-Cinnamoyltropolones

3-Acetyltropolone (1) reacted with phenylhydrazine to give 3-acetyltropolone phenylhydrazone (3) and 3-methyl-1-phenyl-1,8-dihydrocycloheptapyrazol-8-one (4). The former (3) cyclized to afford the latter (4). The reaction of 3-acetyl-2-methoxytropone (2a) with phenylhydrazine gave 4, 3-methyl-2-phenyl-2,8-dihydrocyclo-heptapyrazol-8-one (5), and 3-methyl-2-phenyl-2,8-dihydrocycloheptapyrazol-8-one phenylhydrazone (6). The compound (5) reacted with phenylhydrazine to afford 6. The reaction of 7-acetyl-2-methoxytropone (2b) with phenylhydrazone gave 7-acetyl-2-methoxytropone phenylhydrazone (7), 7-acetyl-2-(N′-phenylhydrazino)-tropone phenylhydrazone (8), 3-methyl-1-phenyl-1,8-dihydrocycloheptapyrazol-8-one phenylhydrazone (9), and 6. The compound (7) was heated to afford 4 and reacted with phenylhydrazine to afford 8 and 9. The compound (8) was also refluxed to give 9.

Synthesis of 1,8‐ and 2,8‐dihydrocycloheptapyrazol‐8‐one derivatives by the reactions of 3‐acetyltropolone and its methyl ethers with phenylhydrazine

Reactions of 3-acetyltropolone methyl ethers with o-phenylenediamine are described. 3-Acetyl-2-methoxytropone (2a) with o-phenylenediamine in ethanol under reflux condition to afford 11-hydroxy-6-methylcyclohepta[b][1,5]benzodiazepine (4), 10-acetyl-6H-cyclohepta[b]quinoxaline (5), and 6-acetyl-5H-cyclohepta[b]-quinoxaline (6). The same reaction of 7-acetyl-2-methoxytropone (2b) gave 7-acetyl-2-(2-aminoanilino)-tropone (3b) besides 4, 5, and 6. The compound 4 has a 1,4-diazaheptalene skeleton.

Akio Yamane

Papers

Reactions of 3-acetyltropolone and its methyl ethers with hydrazine.

Synthesis and Cyclization of 3-Cinnamoyltropolones

Synthesis of 1,8‐ and 2,8‐dihydrocycloheptapyrazol‐8‐one derivatives by the reactions of 3‐acetyltropolone and its methyl ethers with phenylhydrazine

Reactions of 3-acetyltropolone methyl ethers with o-phenylenediamine. Formation of cyclohepta[b][1,5]benzodiazepine

Reactions of 3-acetyltropolone and its methyl ethers with methylhydrazine