title: Activation of electrophilicity of stable Y-delocalized carbamate cations in intramolecular aromatic substitution reaction: evidence for formation of diprotonated carbamates leading to generation of isocyanates.
abstract: Although cations with three heteroatoms, such as monoprotonated guanidine and urea, are stabilized by Y-shaped conjugation and such Y-conjugated cations are sufficiently basic to be further protonated (or protosolvated) to dications in strongly acid media, only O-monoprotonated species have been detected in the case of carbamates even in magic acid. We found that the trifluoromethanesulfonic acid-catalyzed cyclization of arylethylcarbamates proceeds to afford dihydroisoquinolones in high yield. In strong acids, methyl carbamates are fully O-monoprotonated, and these monocations do not undergo cyclization even under heating. But, as the acidity of the reaction medium is further increased, the cyclization reaction of methyl phenethylcarbamates starts to proceed as a first-order reaction, with a linear relationship between rate and acidity. The sign and magnitude of the entropy of activation ΔS(‡) were found to be similar to those of other A(Ac)1 reactions. These results strongly support the idea that further protonation of the O-protonated carbamates is involved in the cyclization, but the concentration of the dications is very low and suggests that the rate-determining step is dissociation of methanol from the diprotonated carbamate to generate protonated isocyanate, which reacts with the aromatic ring. Therefore, O-protonated carbamates are weak bases in sharp contrast to other Y-shaped monocations.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kurouchi
authors.forename: Kyoko
authors.initials: K
authors.lastname: Kawamoto
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nakamura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Otani
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Ohwada
mesh_terms: D002219:Carbamates / Q000737:chemistry*; D002412:Cations / Q000737:chemistry; D017953:Isocyanates / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011522:Protons
chemical_list: D002219:Carbamates; D002412:Cations; D017953:Isocyanates; D011522:Protons