Enols of Substituted Cyanomalonamides

Twenty open-chain mono-, di-, and trialkyl and aryl-N-substituted cyanomalonamides R²R¹NCOCH(CN)CONHR³ were prepared. In solution, signals for both amide and a single enol are mostly observed, despite the potential for E and Z isomeric enols. The equilibrium (K_Enol) values between the amides and the enols were determined in different solvents by NMR spectra. They decrease on increasing the polarity of the solvent in the order CDCl₃ ∼ C₆D₆ > THF-d₈ > (CD₃)₂CO > CD₃CN > DMF-d₇ > DMSO-d₆. For the R¹R²NCOCH(CN)CONHR³ system when R¹ = R² = H, Me or R¹ = H, R² = Me, K_Enol for R³ follows the order:  C₆F₅ > Ph ≥ An ≥ i-Pr ≥ t-Bu, and for R¹, R²:H, H > Me, H > Me, Me in all solvents. A unique feature is the appreciable % enol in DMSO-d₆ when R¹ = R² = H, in contrast with enol systems with other electron-withdrawing groups (EWGs). Calculations (B3LYP/6-31G**) corroborate the higher K_Enol values for less alkyl-substituted systems, showing that in the most stable conformer when R¹ = H, R² = R³ = Me the N-hydrogens are closer to the CN group. The order of promoting substituents for enol of amide formation is CONH₂ > CO₂CH₂CF₃ > CO₂Me > CONHMe. The solid-state structures of the isolated species, determined by X-ray crystallography, were either amides or enols, and a higher K_Enol(CDCl₃) value does not ensure a solid enol structure. In no system were both solid species isolated. The X-ray structures of the enols were temperature-dependent. In most cases, the difference between the O−H and O···H bond lengths at low temperature were appreciable, but they become closer at the higher temperature. Similar tendency for either the CC/C−C or the C−O/CO bonds was observed. This is ascribed to a hydrogen shift between two regioisomeric enols in an asymmetric double-well potential, which becomes faster at a higher temperature. Calculations show that the enol structures are nonsymmetrical, resembling the lower temperature structures, even when they are chemically symmetrical, but the energy differences between the two regioisomers are <1 kcal. The hydrogen bonds in the enol moiety are strong, with O···O distances <2.45 Å, and are resonance-assisted hydrogen bonds. IR spectra in solution and the solid state qualitatively corroborate the NMR and X-ray structure determination.