Tautomerism and isotopicmultiplets in the 13C NMR spectra of partially deuterated 3-arylpyrimido[4,5-c]pyridazine-5,7(6H,8H)- diones and their sulfur analogs – evidence for elucidation of the structure backbone and tautomeric forms

摘要

Thetautomerismof the synthesized 3-arylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones (1a–d)and3-aryl-7-thioxo-7,8-dihydro- 6H-pyrimido[4,5-c]pyridazine-5-ones (2a–d) was studied in dimethyl sulfoxide (DMSO)-d6. 1H NMR spectra of 1a–d showed a clustered water molecule in the structure backbone that is attached by strong intermolecular H bonding. The relation between the temperature and H bonding of the clustered water molecule with 1a was also studied as representative. The relation between the electronegativity (χ) of the substituent on phenyl ring and the chemical shifts of clustered water protons in 1a–d was also studied. All of 1a–d and also 2d compounds existed in lactam (I) form, whereas 2a–c compounds have two distinguished tautomers in DMSO-d6 [lactam (I) and lactim (II) forms]. The solvent-substrate proton exchange was examined in compounds 1a–d and 2a–d by adding one drop of D2O. All compounds (except 1d) showed proton/deuterium exchange of the clustered water protons in DMSO by adding one drop of D2O. Some compounds (but not all of them) that are easily soluble in DMSO-d6 containing D2O showed isotopic splitting (β-isotope effect) in their 13C NMR spectra. Among them, compound 1a was the best evidence to help the spectral assignments and structure determination of predominant tautomer by carbon-13 splitting (β-isotope effect).