Influence of competing A^1,3 -strain on the conformational preferences of <i>N</i>₁, <i>N</i>₄-diformylpiperazines

Abstract

The conformational preferences of <i>N</i>₁, <i>N</i>₄-diformylpiperazines <b>9-12</b> have been studied using <b>NMR</b> spectral techniques and semi empirical molecular orbital calculations. Each of the diformylpiperazines <b>9-11</b> have been found to exist as an equilibrium mixture of four rotamers resulting from the restricted <i>N</i>-C rotation at the two <i>N</i>-C=O bonds. All the four rotamers (<i>anti-anti, anti-syn, syn-anti, syn-syn</i>) of <b>9</b> are found to adopt the twist-boat (<b>B4</b>) conformations. Similarly all the four rotamers of <b>11</b> prefer flipped chair (<b>CA</b>) conformations. On the other hand the diformylpiperazine <b>10</b> has been found to adopt different ring conformations depending upon the <i>N</i>-CHO rotameric states (<b>B4</b> for the rotamer <b>A</b>, <b>B3</b> in the cases of rotamers <b>B</b> and <b>D</b>, and <b>CA</b> for the rotamer C). The A^1,3-strain and the resonance energy (arising from the delocalisation of the lone pair of electrons on the nitrogen) have been found to be the most important factors in determining the conformational preferences of all the piperazines investigated. The semiempirical molecular orbital calculations supported

the conformational preferences and the nature of the conformational equilibria derived from the NMR results.