Imidoyl Azide to Tetrazole Cyclization Limited by Internal Hydrogen Bonding and Imine Isomerization

Article abstract of DOI:10.1021/jo00320a022

The rates of cyclization of the 2-azido-3-benzoyl enamine 6 to the corresponding tetrazole 9 have been measured in D2O as a function of pD at 25 deg C.A complex pD-rate profile is observed with a maximum rate at a pD of ca. 2.0.The observed rate constants are reduced (typically 7-fold) in D2O in those regions where proton transfer to the enamine is rate determining; however, the actual rate of isomerization about the iminium ion intermediate (C=N⁺) remains unchanged in D2O, indicating that the solvent most likely does not add reversibly in the slow step for isomerization.The imidoyl azide 15 is stabilized in the open-chain azido form by internal hydrogen bonding to the o-OH group.Both the neutral (15) and anionic (16) forms cyclize to the tetrazole 18, the latter 35-fold more rapidly.The protonated species 17 does not cyclize to the tetrazole and is inert to hydrolysis.