Enols of Substituted Cyanomalonamides

Twenty open-chain mono-, di-, and trialkyl and aryl-<i>N</i>-substituted cyanomalonamides R<sup>2</sup>R<sup>1</sup>NCOCH(CN)CONHR<sup>3</sup> were prepared. In solution, signals for both amide and a single enol are mostly observed, despite the potential for <i>E</i> and <i>Z</i> isomeric enols. The equilibrium (<i>K</i><sub>Enol</sub>) 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 CDCl<sub>3</sub> ∼ C<sub>6</sub>D<sub>6</sub> > THF-<i>d</i><sub>8</sub> > (CD<sub>3</sub>)<sub>2</sub>CO > CD<sub>3</sub>CN > DMF-<i>d</i><sub>7</sub> > DMSO-<i>d</i><sub>6</sub>. For the R<sup>1</sup>R<sup>2</sup>NCOCH(CN)CONHR<sup>3</sup> system when R<sup>1</sup> = R<sup>2</sup> = H, Me or R<sup>1</sup> = H, R<sup>2</sup> = Me, <i>K</i><sub>Enol</sub> for R<sup>3</sup> follows the order:  C<sub>6</sub>F<sub>5</sub> > Ph ≥ An ≥ <i>i</i>-Pr ≥ <i>t</i>-Bu, and for R<sup>1</sup>, R<sup>2</sup>:H, H > Me, H > Me, Me in all solvents. A unique feature is the appreciable % enol in DMSO-<i>d</i><sub>6</sub> when R<sup>1</sup> = R<sup>2</sup> = H, in contrast with enol systems with other electron-withdrawing groups (EWGs). Calculations (B3LYP/6-31G**) corroborate the higher <i>K</i><sub>Enol</sub> values for less alkyl-substituted systems, showing that in the most stable conformer when R<sup>1</sup> = H, R<sup>2</sup> = R<sup>3</sup> = Me the <i>N</i>-hydrogens are closer to the CN group. The order of promoting substituents for enol of amide formation is CONH<sub>2</sub> > CO<sub>2</sub>CH<sub>2</sub>CF<sub>3</sub> > CO<sub>2</sub>Me > CONHMe. The solid-state structures of the isolated species, determined by X-ray crystallography, were either amides or enols, and a higher <i>K</i><sub>Enol</sub>(CDCl<sub>3</sub>) 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.