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3‐Hydroxy‐2‐cyanoalk‐2‐enamides, and 2‐Cyano‐2‐(tetrahydrofuran‐2‐ylidene)‐ and 2‐Cyano‐2‐(tetrahydropyran‐2‐ylidene)acetamides: Synthesis, structure, and solvent‐dependent ( Z )/( E )‐isomerism
Author(s) -
Papageorgiou Christos,
Akyel Kayhan,
Borer Xaver,
Oberer Lukas,
Rihs Grety
Publication year - 1998
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19980810542
Subject(s) - chemistry , tetrahydropyran , tetrahydrofuran , isomerization , intramolecular force , stereochemistry , solvent , nuclear magnetic resonance spectroscopy , substituent , aryl , medicinal chemistry , crystallography , alkyl , ring (chemistry) , organic chemistry , catalysis
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 1 H‐NMR ROESY spectroscopy at room temperature. The enolic compounds 1 – 3 adopt an extended conformation stabilized by a strong intramolecular OH … OC bond both in the solid state and in (D 6 )DMSO solution. In contrast, the structure of the cyclic derivatives 5a , b – 8a , b is solvent‐dependent. In the solid state and in CDCl 3 solution, the compounds adopt an extended conformation of type I or III , while, in (D 6 )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 7b having the highest barrier of rotation around the CC 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.