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 (KEnol) 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, KEnol 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 KEnol 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 KEnol(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

二十种由单、双、三烷基和芳基-N-取代氰基苹果酸酰胺R2R1NCOCH(CN)CONHR3组成的开链化合物得以合成。在溶液状态下，尽管存在E和Z异构的烯醇可能，但仍主要观察到酰胺和单一烯醇的信号。通过核磁共振波谱在不同溶剂中确定了酰胺与烯醇之间的平衡（KEnol）值。这些值随着溶剂极性的增加而降低，其顺序为CDCl3 ∼ C6D6 > THF-d8 > (CD3)2CO > CD3CN > DMF-d7 > DMSO-d6。对于R1R2NCOCH(CN)CONHR3系统，当R1 = R2 = H，Me或R1 = H，R2 = Me时，烯醇的KEnol对于R3的顺序为：C6F5 > Ph ≥ An ≥ i-Pr ≥ t-Bu，而对于R1，R2:H，H > Me，H > Me，Me在所有溶剂中。一个独特的特征是，当R1 = R2 = H时，DMSO-d6中可观的烯醇百分比，与其他具有吸电子基团（EWGs）的烯醇系统形成鲜明对比。B3LYP/6-31G**计算证实了较少烷基取代系统的KEnol值较高，表明在最稳定的构象中，当R1 = H，R2 = R3 = Me时，N-氢原子更接近CN基团。促进酰胺形成烯醇的取代基顺序为CONH2 > CO2CH2CF3 > CO2Me > CONHMe。通过X射线晶体学确定的孤立物种的固态结构要么是酰胺要么是烯醇，且KEnol(CDCl3)值较高并不确保固态烯醇结构。在没有任何系统中都分离出固态两种物种。烯醇的X射线结构受温度影响。在大多数情况下，低温时O−H和O···H键长的差异显著，但在较高温度时变得接近。对于CC/C−C或C−O/CO键也观察到类似的趋势。这归因于在非对称双阱势中两个区域异构烯醇之间的氢转移，该转移在较高温度时变得更快。计算表明，烯醇结构是非对称的，类似于低温结构，即使它们在化学上是对称的，但两个区域异构体之间的能量差异