Takashi Keumi

Ortho-selective side-chain nitration of α-Bromoacylpolymethylbenzenes and its application to the syntheses of indan-1-one and inden-1-one derivatives

Abstract α-Bromoacylpolymethylbenzenes 2a-m react with fuming nitric acid in acetic anhydride to give 2-(nitromethyl)-(α-bromoacyl)polymethylbenzenes 3a-m in good isolated yields. Compounds 3a-j undergo the intramolecular nucleophilic substitution/cyclization in the presence of 1 equiv. of base either in benzene or N,N -dimethylformamide (DMF) to provide the corresponding substituted 3-nitroindan-1-ones 4a-j in quantitative yields as mixtures of diastereomers ( cis and trans ). The cis/trans ratios of 4 vary with the steric factor and the nature of solvent: cis trans in benzene, whereas cis > trans in DMF. On the contrary, 3-unsubstituted 2-nitromethyl compounds 3k-m afford 3,2-benzoxazepin-5(4 H )-ones 7k-m under the same reaction condition. On the other hand, the reactions of 3a-j in the presence of 2 equiv. of base give the substituted inden-1-ones 5 in satisfactory isolated yields.

Solvent effects on isomer distributions and relative rates in Friedel–Crafts benzylation and benzoylation of dibenzofuran derivatives

The positional reactivity order in Friedel–Crafts benzoylation and benzylation of dibenzofuran (DBF) is found to be 2 > 3 > 1 4. Both the partial rate factors and the positional selectivity for the benzylation of DBF are very low compared with those of benzoylation. In competitive benzoylation of 1,2,3,4-tetramethyldibenzofuran (TMD)versus DBF, a large solvent effect has been observed on the relative rate (TMD versus DBF) as well as on the isomer ratio of 8- to 7-benzoyl-TMD, which appears to be due to the difference in solvation of the intermediate σ-complex leading to each of the products. In contrast, in the case of competitive benzylation of TMD versus DBF, neither solvent effect on the relative rate nor any isomer ratio was observed. The nature of the transition state determining the relative rate and the positional reactivity for benzylation has been deduced from these results.

Solvent effects on isomer distributions in acylation of 1,2,3,4-tetramethyldibenzofuran: regiospecific solvation of the intermediate σ-complex

A large solvent effect is observed in Friedel–Crafts acylation of 1,2,3,4-tetramethyldibenzofuran (TMD). 8-Acyl-TMD is by far the major product in nitrohydrocarbons while 7-acyl-TMD is favoured in chloro-hydrocarbons and is the major product in many cases. The influence of temperature, and the nature of the reaction medium, acylating agents, and added nitro-compounds on the isomer distribution, are examined in detail. It is demonstrated that neither rearrangement of the products, nor thermodynamic differences between the 7-and 8-position of TMD, nor reduction in electrophilicity of the acylium ion by solvation are responsible for the solvent effect. Specific association of a nitrohydrocarbon solvent with the intermediate σ-complex leading to 8-acyl-TMD is presented as the pathway of the reaction.

Convenient synthesis of 4-nitrotetralones by selective side-chain nitration of methyl-substituted acryloylbenzenes, followed by intramolecular Michael reaction

Reaction of polymethyl-substituted acryloylbenzenes (1) with fuming nitric acid in acetic anhydride gave the products (2) derived from selective side-chain nitration at the ortho-position; the subsequent intramolecular Michael reaction leads to exclusive formation of 4-nitrotetralones (3).

Trifluoroacetic acid-catalysed transacylation of arenes by acylpentamethylbenzene

Facile transacylation between acylpentamethylbenzene and activated arenes such as anisole was found to occur in boiling trifluoroacetic acid (TFA). The mechanism for the transacylation between acetylpentamethylbenzene (AcPMB) and anisole with TFA was elucidated by means of product isolation and kinetics. The reaction proceeds via reversible protodeacetylation of AcPMB involving an ipso-protonated intermediate B to give pentamethylbenzene and acetic trifluoroacetic anhydride followed by irreversible acetylation of anisole by the mixed anhydride. The mechanism resulting in an ipso-protonated intermediate B was deduced from the reaction of acetylmesitylene with [2H]TFA as well as from the rate of deacetylation of 3,5-dideuterioacetylmesitylene with TFA. The formation of such an intermediate was also independently confirmed by 13C n.m.r. spectroscopic studies on AcPMB in superacid solutions under stable ion conditions.