Cucurbit[n]uril analogues: synthetic and mechanistic studies

reaction: see text] The synthesis of cucurbitn]uril analogues (18, 19, (+/-)-20, 33, 34, 35, 36, and 37) is presented. These CB5], CB6], and CB7] analogues all contain bis(phthalhydrazide) walls that are incorporated into the macrocycle. The tailor-made synthesis of these CBn] analogues proceeds by the condensation of the appropriate bis(electrophile) (4, 7, or 9) with bis(phthalhydrazide) (17), which delivers the CB6] and CB7] analogues in good yield, whereas the CB5] analogue is formed in low yield. To improve the solubility characteristics of the CBn] analogues for recognition studies in water or organic solution, the CO2Et groups were transformed to CO2H and CO2(CH2)9CH3 groups. On the basis of the results of product resubmission experiments, we conclude that these macrocycles are kinetic products. To help rationalize the good yields obtained in the CB6] and CB7] analogue macrocyclization reactions, we performed mechanistic studies of model methylene bridged glycoluril dimers, which suggest an intramolecular isomerization during CBn] analogue formation.