Synthesis and stereochemistry of dispiro substituted pyridazines: application of ellipticity-absorbance ratio spectra for proving enantiomeric relationship by HPLC-CD/UV detection

The aim of our study was to synthesize vinylic and pyrido-fused pyridazines with a spirano moiety and to investigate their stereochemistry by spectroscopic and HPLC analyses. The vinylic compounds 5 were obtained by Knoevenagel condensation of cyclohexylidene malonates 1 with pyridazinecarbaldehyde 2. Compound 5b exhibits geometric isomerism identified by NMR, HPLC, and X-ray methods. The thermal rearrangement reactions of compounds 5 easily led to the pyridopyridazine derivatives 6. In the case of 6b, possessing both central and axial chirality, both diastereomers and the respective enantiomers were detected. Their stereochemical relationships could be determined by HPLC-CD/UV analyses with application of anisotropy spectra in a novel way.