3-hydroxy-2-cyanoalk-2-enamides, and 2-cyano-2-(tetrahydrofuran2- ylidene)- and 2-cyano-2-(tetrahydropyran-2-ylidene)acetamides: Synthesis, structure, and solvent-dependent (Z)/(E)-isomerism

Article abstract of DOI:10.1002/hlca.19980810542

3-Hydroxy-2-cyanoalk-2-enamides, and 2-cyano-2-(tetrahydrofuran-2- ylidene)- and 2-cyano-2-(tetrahydropyran-2-ylidene)acetamides with N-alkyl and N-aryl substituents have been synthesized in three steps from cyanoacetic acid. Their conformations were investigated by X-ray crystallography and ¹H- NMR ROESY spectroscopy at room temperature. The enolic compounds 1-3 adopt an extended conformation stabilized by a strong intramolecular O-H O=C bond both in the solid state and in (D₆)DMSO solution. In contrast, the structure of the cyclic derivatives 5a,b-8a,b is solvent-dependent. In the solid state and in CDCI₃ solution, the compounds adopt an extended conformation of type I or III, while, in (D₆)DMSO solution, their structures undergo time-dependent (Z)/(E)-isomerization structures (of type II or IV). This observation is compatible with a dipolar transition state of rotation. The kinetics of the isomerization are controlled by the N-substituent, the N-(t-Bu) derivatives 7a and 71) having the highest barrier of rotation around the C=C bond. The whole body of experimental evidence together with the results of molecular- mechanics calculations with I-IV, indicate that, in DMSO, two (E)/(Z)- isomers with two conformations are present, and that they undergo interconversion at room temperature with four different constants. The very fast exchange rates k(I.II) and k(III.IV) in the NMR time-scale might be responsible for the detection of only two isomers.