title: Mechanisms of tetrazole formation by addition of azide to nitriles.
abstract: It is well-known that azide salts can engage nitriles at elevated temperatures to yield tetrazoles; however, there is continued debate as to the mechanism of the reaction. Density functional theory calculations with the hybrid functional B3LYP have been performed to study different mechanisms of tetrazole formation, including concerted cycloaddition and stepwise addition of neutral or anionic azide species. The calculations presented here suggest a previously unsuspected nitrile activation step en route to an imidoyl azide, which then cyclizes to give the tetrazole. The activation barriers are found to correlate strongly with the electron-withdrawing potential of the substituent on the nitrile.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Fahmi
authors.initials: F
authors.lastname: Himo
authors.forename: Zachary P
authors.initials: ZP
authors.lastname: Demko
authors.forename: Louis
authors.initials: L
authors.lastname: Noodleman
authors.forename: K Barry
authors.initials: KB
authors.lastname: Sharpless
mesh_terms: D001386:Azides / Q000737:chemistry*; D003500:Cyclization; D008958:Models, Molecular; D009570:Nitriles / Q000737:chemistry*; D013777:Tetrazoles / Q000138:chemical synthesis*; D013816:Thermodynamics
chemical_list: D001386:Azides; D009570:Nitriles; D013777:Tetrazoles