Nucleophilic Reactivities of Indoles

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• 作者：Sami Lakhdar ; Martin Westermaier ; Franç ; ois Terrier ; Ré ; gis Goumont ; Taoufik Boubaker ; Armin R. Ofial ; Herbert Mayr
• 刊名：Journal of Organic Chemistry
• 出版年：2006
• 出版时间：November 24, 2006
• 年：2006
• 卷：71
• 期：24
• 页码：9088 - 9095
• 全文大小：202K
• 年卷期：v.71,no.24(November 24, 2006)
• ISSN：1520-6904

文摘

The kinetics of the coupling of indole (1a), N-methylindole (1b), 5-methoxyindole (1c), and 5-cyanoindole(1d) with a set of reference benzhydryl cations have been investigated in acetonitrile and/ordichloromethane. The second-order rate constants for the reactions correlate linearly with the electrophilicityparameter E of the benzhydryl cations. This allows the determination of the reactivity parameters, N ands, characterizing the nucleophilicity of 1a-d according to the linear free enthalpy relationship log k(20C) = s(N + E) (Acc. Chem. Res. 2003, 36, 66). The nucleophilicity parameters thus defined describenicely the reactions of 1a-d with 4,6-dinitrobenzofuroxan (2), a neutral superelectrophilic heteroaromaticwhose electrophilicity (E) has been recently determined. On this ground, the kinetics of the coupling of2 with a large variety of indole structures have been studied in acetonitrile, leading to a ranking of thisfamily of -excessive carbon nucleophiles over a large domain of the nucleophilicity scale N. Importantly,two linear and parallel correlations are obtained on plotting the measured N values versus the pK_a(H₂O)values for protonation at C-3 of 5-X-substituted indoles and 5-X-substituted 2-methylindoles, respectively.This splitting reveals that the presence of the 2-methyl group causes steric hindrance to the approach of2 from the adjacent C-3 position of an indole structure. The N vs pK_a(H₂O) correlation for 5-X-substitutedindoles is used for a rapid determination of the C-3 basicity of indoles whose acidity constants cannot bemeasured through equilibrium studies in strongly acidic aqueous media.