Conformational features of secondary N-cyclopropyl amides

J Org Chem. 2015 Apr 17;80(8):3914-20. doi: 10.1021/acs.joc.5b00236. Epub 2015 Apr 8.

Abstract

NMR studies in conjunction with ab initio calculations revealed unexpected conformational behavior of N-cyclopropylacetamide (1). This secondary amide displays 16-19% E-rotamer (cis) around the carbonyl-nitrogen bond in apolar solvents, in contrast to other aliphatic secondary acetamides in which significant E-rotamer populations are rare due to steric contacts between the substituents on the amide bond. In addition, 1 adopts an ortho conformation around the N-cPr bond instead of the anti conformation generally preferred by secondary acetamides. This distinct conformational behavior was also observed for other secondary N-cyclopropyl amides.