The mechanism of the acid-dependent interring dehydrogenation in the conversion of the single-bonded 3-phenyl-2H-1,4-benzothiazine dimer 2 to the Δ2,2′-bi(2H-1,4-benzothiazine) scaffold of red hair pigments is disclosed herein. Integrated chemical oxidation and oxygen consumption experiments, coupled with electron paramagnetic resonance (EPR) analyses and DFT calculations, allowed the identification of a key diprotonated free-radical intermediate, which was implicated in a remarkable oxygen-dependent chain process via peroxyl radical formation and evolution to give the Δ2,2′-bi(2H-1,4-benzothiazine) dimer 3 by interring dehydrogenation. The critical requirement for strongly acidic conditions was rationalized for the first time by the differential evolution channels of isomeric peroxyl radical intermediates at the 2- versus 3-positions. These results offer for the first time a rationale to expand the synthetic scope of the double interring dehydrogenation pathway for the preparation of novel symmetric double-bond bridged captodative heterocycles.
Proton-Sensitive Free-Radical Dimer Evolution Is a Critical Control Point for the Synthesis of Δ2,2'-Bibenzothiazines / Valgimigli L.; Alfieri M.L.; Amorati R.; Baschieri A.; Crescenzi O.; Napolitano A.; D'ischia M.. - In: JOURNAL OF ORGANIC CHEMISTRY. - ISSN 0022-3263. - STAMPA. - 85:17(2020), pp. 11440-11448. [10.1021/acs.joc.0c01520]
Proton-Sensitive Free-Radical Dimer Evolution Is a Critical Control Point for the Synthesis of Δ2,2'-Bibenzothiazines
Valgimigli L.
;Amorati R.;Baschieri A.;
2020
Abstract
The mechanism of the acid-dependent interring dehydrogenation in the conversion of the single-bonded 3-phenyl-2H-1,4-benzothiazine dimer 2 to the Δ2,2′-bi(2H-1,4-benzothiazine) scaffold of red hair pigments is disclosed herein. Integrated chemical oxidation and oxygen consumption experiments, coupled with electron paramagnetic resonance (EPR) analyses and DFT calculations, allowed the identification of a key diprotonated free-radical intermediate, which was implicated in a remarkable oxygen-dependent chain process via peroxyl radical formation and evolution to give the Δ2,2′-bi(2H-1,4-benzothiazine) dimer 3 by interring dehydrogenation. The critical requirement for strongly acidic conditions was rationalized for the first time by the differential evolution channels of isomeric peroxyl radical intermediates at the 2- versus 3-positions. These results offer for the first time a rationale to expand the synthetic scope of the double interring dehydrogenation pathway for the preparation of novel symmetric double-bond bridged captodative heterocycles.File | Dimensione | Formato | |
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