title: Nucleophilic reactivities of indoles.
abstract: 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/or dichloromethane. The second-order rate constants for the reactions correlate linearly with the electrophilicity parameter E of the benzhydryl cations. This allows the determination of the reactivity parameters, N and s, characterizing the nucleophilicity of 1a-d according to the linear free enthalpy relationship log k(20 degrees C) = s(N + E) (Acc. Chem. Res. 2003, 36, 66). The nucleophilicity parameters thus defined describe nicely the reactions of 1a-d with 4,6-dinitrobenzofuroxan (2), a neutral superelectrophilic heteroaromatic whose electrophilicity (E) has been recently determined. On this ground, the kinetics of the coupling of 2 with a large variety of indole structures have been studied in acetonitrile, leading to a ranking of this family of pi-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)(H(2)O) 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 of 2 from the adjacent C-3 position of an indole structure. The N vs pK(a)(H(2)O) correlation for 5-X-substituted indoles is used for a rapid determination of the C-3 basicity of indoles whose acidity constants cannot be measured through equilibrium studies in strongly acidic aqueous media.
authors.affiliation: Laboratoire SIRCOB, UMR 8180, Institut Lavoisier, Université de Versailles, 45, Avenue des Etats-Unis, 78035 Versailles Cedex, France.
authors.forename: Sami
authors.initials: S
authors.lastname: Lakhdar
authors.forename: Martin
authors.initials: M
authors.lastname: Westermaier
authors.forename: François
authors.initials: F
authors.lastname: Terrier
authors.forename: Régis
authors.initials: R
authors.lastname: Goumont
authors.forename: Taoufik
authors.initials: T
authors.lastname: Boubaker
authors.forename: Armin R
authors.initials: AR
authors.lastname: Ofial
authors.forename: Herbert
authors.initials: H
authors.lastname: Mayr
mesh_terms: D007211:Indoles / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D016339:Spectrometry, Mass, Fast Atom Bombardment
chemical_list: D007211:Indoles