Synthesis, X-ray analysis and spectroscopic characterization of the hemiaminal cyclization product from 2,4-dipyridine substituted 3,7-diazabicyclo[3.3.1]nonanone 1,5-diesters

The Synthesis and Structural Characterisation of a Series of Hydrophobic Piperidones and Bispidones

“…The three bispidone structures all show a double-chair conformation of the bicyclic ring system (as has been observed for other uncomplexed bispidone systems containing two CO 2 Me groups) [5][6][7]10,25] and is shown for compound 2 in Figure 9. The structure shows the pyridyl rings in a cissym orientation, which confirms the solution NMR spectroscopic data.…”

“…The rigidity of the bispidone backbone is important to medicinal chemists studying the affinity of the molecule to opioid receptors. [4][5][6] Even subtle changes in the substituents on the bispidone ring can result in a complete loss of affinity. Bispidones have also received attention in coordination chemistry, because replacement of the skeletal carbon atoms at the 3-and 7-positions by groups containing possible donor atoms such as nitrogen can result in the bispidone becoming a tetra-, penta-or hexadentate ligand, depending on the substituents attached to the heteroatoms at these positions ( Figure 1).…”

“…[23] The bicyclic bispidones tend to adopt either a double-chair or a chair-boat conformation, with studies showing that systems where the two ring nitrogen atoms are markedly pyramidal tend to adopt chair-boat conformations, whilst the double-chair conformation is preferred for systems with planar nitrogen atoms. [24] All examples containing diester substituents as shown in Figure 1 (nine reported in the CCDC database) [5][6][7]10,18,25] feature the bicyclic backbone with a double-chair conformation. Whilst this backbone is preorganised for metal coordination, in all the examples featuring pyridyl groups the donor atoms are located away from the metal coordination site, in contrast to the orientation of the pyridyl groups in the metal complexes.…”

Bispidine Coordination Chemistry

“…The N3 Á Á ÁN7 distances decrease to 2.66 Å , due to relief of the lonepair repulsion. Only three published X-ray data sets of diprotonated molecules with the bispidine backbone in the cc conformation exist (145)(146)(147). On the basis of PM3 calculations, it has been shown for several bispidinines that the singly protonated forms prefer the cc conformation, and these have low activation barriers for proton exchange between the two nitrogen centers.…”

“…The 1 H-NMR spectra show a loss of symmetry of the compound, which can be explained by the formation of the hemiaminal cyclization product 105 (see Chart 19) (23,164). This unusual product also yielded crystals for X-ray analysis (147).…”