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 H-1 NMR spectra of dihydrodiazocinone la 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 H-1 NMR between 21 and 70 degrees C in DMSO Solution. yield an activation energy of similar to 21 kcal/mol relative to the kinetic conformer and show an equilibrated ratio of similar to 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.