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J Org Chem. 2005 Jun 24;70(13):5144-9.

Electron-transfer mechanism in the N-demethylation of N,N-dimethylanilines by the phthalimide-N-oxyl radical.

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  • 1Dipartimento di Chimica, Universit√† degli Studi di Roma La Sapienza, Piazzalle A. Moro 5, I-00185 Rome, Italy.


The reactivity of the phthalimide N-oxyl radical (PINO) toward the N-methyl C-H bond of a number of 4-X-substituted N,N-dimethylanilines (X = OMe, OPh, CF(3), CO(2)Et, CN) has been investigated by product and kinetic analysis. PINO was generated in CH(3)CN by reaction of N-hydroxyphthalimide (NHPI) with Pb(OAc)(4) or, for the kinetic study of the most reactive substrates (X = OMe, OPh), with tert-butoxyl radical produced by 266 nm laser flash photolysis of di-tert-butyl peroxide. The reaction was found to lead to the N-demethylation of the N,N-dimethylaniline with a rate very sensitive to the electron donating power of the substituent (rho(+) = -2.5) as well as to the oxidation potential of the substrates. With appropriately deuterated N,N-dimethylanilines the intermolecular and intramolecular deuterium kinetic isotope effects (DKIEs) were measured for some substrates (X = OMe, CO(2)Et, CN) with the following results. First, intramolecular DKIE [(k(H)/k(D))(intra)] was found to be always different and higher than intermolecular DKIE [(k(H)/k(D))(inter)]; second, no intermolecular DKIE [(k(H)/k(D))(inter) = 1] was observed for X = OMe, whereas substantial values of (k(H)/k(D))(inter) were exhibited by X = CO(2)Et (4.8) and X = CN (5.8). These results, while are incompatible with a single step hydrogen atom transfer from the N-C-H bond to the N-oxyl radical, as proposed for the reaction of PINO with benzylic C-H bonds, can be nicely interpreted on the basis of a two-step mechanism involving a reversible electron transfer from the aniline to PINO leading to an anilinium radical cation, followed by a proton-transfer step that produces an alpha-amino carbon radical. In line with this conclusion the reactivity data exhibited a good fit with the Marcus equation and a lambda value of 37.6 kcal mol(-1) was calculated for the reorganization energy required in this electron-transfer process. From this value, a quite high reorganization energy (>60 kcal mol(-1)) is estimated for the PINO/NHPI(-H)(-) self-exchange reaction. It is suggested that the N-demethylated product derives from the reaction of the alpha-amino carbon radical with PINO to form either a cross-coupling product or an alpha-amino carbocation. Both species may react with the small amounts of H(2)O present in the medium to form a carbinolamine that, again by hydrolysis, can be eventually converted into the N-demethylated product.

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