Tautomerism and isotopic multiplets 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

Abstract

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).

ZrOCl2.8H2O as a green and efficient catalyst for the expeditious synthesis of substituted 3-arylpyrimido[4,5-c]pyridazines in water

“…Exposure to pyridine has harmful effects on the liver, kidneys, immune systems and reproductive functions, and has potential carcinogenicity. [27][28][29][30][31] Following to recent reports about the application of arylglyoxals (AG) in heterocyclic chemistry, 26,[32][33][34][35][36][37][38][39][40] herein we have applied ZrOCl2•8H2O as recyclable, non-toxic and green catalyst for the regioselective synthesis of 3-arylpyrimido [4,5-c] We also studied the influence of the amount of ZrOCl2•8H2O on the reaction yields. We found that the best yield is obtained when we used the ZrOCl2•8H2O 20 mol% as a catalyst.…”

“…We found that these unexpected signal belong to one clustered water molecule which is located in the molecular network of these heterocyclic systems. 32 The probable structure for the site of linking of the clustered water to the pyrimidopyridazine core was shown in the Fig.1.…”

An Efficient One-pot Two-component Protocol for Regio- and Chemoselective Synthesis of 5-Aryloyl-1,3,7,9-tetraalkyl-2,8-dithioxo-2,3,8,9-tetrahydro-1H-pyrano[2,3-d:6,5-d′]dipyrimidine-4,6(5H,7H)-diones

“…Consequently, MCRs have emerged as a powerful tool for delivering molecular libraries needed in combinatorial approaches for the assembly and lead identification of bioactive compounds. [21] Based on the above considerations and in continuance of our previous research into the arylglyoxal-mediated synthesis of various heterocycles, [22][23][24][25][26][27][28][29][30][31][32] we have found that 1,3-dialkyl thiobarbituric acids undergo a tandem Knoevenagel-Michael condensation with arylglyoxals leading to the formation of a substituted pyranopyrimidine skeleton. Herein, we report an efficient two-component strategy for synthesis of symmetrically substituted 5-aryloyl-1H-pyrano[2,3-d]pyrimidine 1.…”

A Regioselective One-Pot, Three Component Synthesis of 6-Aryl-4-cyano-3(2H)-pyridazinones in Water

“…One-pot multicomponent processes have recently gained a considerable and steadily increasing academic, economic and ecological interest because they address very fundamental principles of synthetic efficiency and reaction design. [6,30,31] As part of our interest in the synthesis of pyridazine systems, [32][33][34] we report herein the one-pot regioselective synthesis of 6-aryl-4-cyano-3(2H )-pyridazinone 7 via reaction of alkyl 2-cyanoacetates 8 with arylglyoxals 9 in the presence of excess hydrazine hydrate (Scheme 1). Previous methods of synthesis involved either the condensation of β,β-dicyanopropiophenone with hydrazine [35] or the reaction of arylglyoxals with hydrazine and ethyl cyanoacetate in a two-step procedure.…”