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 degrees C in DMSO solution, yield an activation energy of approximately 21 kcal/mol relative to the kinetic conformer and show an equilibrated ratio of approximately 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.
Robins
Lori I
LI
Department of Chemistry, One Shields Avenue, University of California, Davis, California 95616, USA.
Carpenter
Richard D
RD
Fettinger
James C
JC
Haddadin
Makhluf J
MJ
Tinti
Dino S
DS
Kurth
Mark J
MJ
D001392:Azocines / Q000737:chemistry*; D018360:Crystallography, X-Ray; D003503:Cyclobutanes / Q000737:chemistry*; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D007555:Isoxazoles / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism; D014227:Triazines / Q000737:chemistry*
D001392:Azocines; D003503:Cyclobutanes; D006571:Heterocyclic Compounds; D007555:Isoxazoles; D014227:Triazines