Enols and thioenols of substituted cyanomonothiocarbonylmalonamides: structures, enolizationvs. thioenolization, equilibria and conformations

Abstract

Condensation of organic isothiocyanates with cyanoacetamides gave 24 N- and N′-substituted cyanomonothiocarbonylmalonamides in different tautomeric ratios i.e., amide–thioamides (TMA) R³NHCSCH(CN)CONR¹R² (12), thioamide–enols of amides (E) R³NHCSC(CN)C(OH)NR¹R² (11) or amide–thioenols (TE) R³NHC(SH)C(CN)CONR¹R² (13). The equilibrium constants (K_thioenol = [TE]/[TMA] and K_enol = [E]/[TMA]) in solution depend on R¹, R², R³ and the solvent. The %(E + TE) for NR¹R² increases in the order NMe₂ < NHMe < NH₂. The (K_thioenol + K_enol) in various solvents follows the order CCl₄ > CDCl₃ > C₆D₆ > THF-d₈ > (CD₃)₂CO > CD₃CN > DMF-d₇ > DMSO-d₆. The δ(OH) values are 16.46–17.43 and the δ(SH) values are 3.87–5.26 ppm in non polar solvents, e.g., CDCl₃ and 6.34–6.97 ppm in THF-d₈ and CD₃CN. An intramolecular O–H⋯O hydrogen bond leads to the preferred Z-configuration of the enols, and an N–H⋯O bond stabilizes the thioenols’ preferred E-configuration with a non-bonded SH in solution. X-Ray crystallography revealed that systems with high %(E + TE) in solution mostly display the enols 11 in the solid state and systems with lower %(E + TE) in solution display structure 12. The differences in δ(OH), δ(NH), K_enol and crystallographic data for analogous enol and thioenol systems are compared.