Influence of competing A1,3-strain on the conformational preferences of N1, N4-diformylpiperazine

The conformational preferences of N-1,N-4-diformylpiperazines 9-12 have been studied using NMR spectral techniques and semiempirical molecular orbital calculations. Each of the diformylpiperazines 9-11 have been found to exist as an equilibrium mixture of four rotamers resulting from the restricted N-C rotation at the two N-C=O bonds. All the four rotamers (anti-anti, anti-syn, syn-anti, syn-syn) of 9 are found to adopt the twist-boat (B4) conformations. Similarly all the four rotamers of 11 prefer flipped chair (CA) conformations. On the other hand the diformylpiperazine 10 has been found to adopt different ring conformations depending upon the N-CHO rotameric states (B4 for the rotamer A, B3 in the cases of rotamers B and D, and CA 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.