Diazocinones: Synthesis and Conformational Analysis

1,2,4,5-Tetrazines (prepared from aryl nitriles) condense with isoxazolylcyclobutanones (prepared from
3-benzenesulfonyl-3-vinylcyclobutanol) in methanolic KOH to give conformationally restricted 6-isoxazol-5-yl-6,7-dihydro-5H-[1,2]diazocin-4-ones. The solution 1H NMR spectra of dihydrodiazocinone 1a with
phenyl moieties at C3 and C8 reveal two conformations of the eight-membered heterocycle that are
non-interconverting on the NMR time scale at ambient temperature. The kinetics of the conversion process,
followed by 1H NMR between 21 and 70 °C in DMSO solution, yield an activation energy of ∼21
kcal/mol relative to the kinetic conformer and show an equilibrated ratio of ∼5:1 of the thermodynamic
to the kinetic conformers. The electronic structure calculations on a model dihydrodiazocinone predict
geometries for the two conformations. One of these geometries agrees with the X-ray crystallographic
analysis of the thermodynamic conformation of 1a.