New one-pot synthesis of spiro[furo[2,3-d]pyrimidine-6,5′-pyrimidine]pentaones and their sulfur analogues
The tautomerism of the synthesized 3-arylpyrimido[4,5-c]pyridazine-5,7(6H,8H)-diones (1a-d) and 3-aryl-7-thioxo-7,8-dihydro-6H-pyrimido[4,5-c]pyridazine-5-ones (2a-d) was studied in dimethyl sulfoxide (DMSO)-d(6). (1)H 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 (chi) 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-d(6) [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 D(2)O. All compounds (except 1d) showed proton/deuterium exchange of the clustered water protons in DMSO by adding one drop of D(2)O. Some compounds (but not all of them) that are easily soluble in DMSO-d(6) containing D(2)O showed isotopic splitting (beta-isotope effect) in their (13)C 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 (beta-isotope effect).