Proton sharing and transfer in some zwitterionic compounds based on 4-oxo-4-((1-phenethylpiperidin-4-yl)(phenyl)amino)alcanoic acids

Three compounds, each derived from Fentanyl and differing essentially only in the length of a carboxylic acid chain, were synthesized and yielded four crystal structures three of which share several structural similarities, including the length of the chain, while the fourth, with a shorter chain, is quite different. The chain length has a significant influence on the crystal structures formed. The 'three atom' chain compounds are all solvated zwitterions which feature a hydrogen-bonded 'dimer' between adjacent zwitterions. The formation of this large dimer leaves available a second carboxylate O atom to take part in hydrogen bonding interactions with solvent molecules. The shorter 'two atom' chain compound was difficult to crystallize and required the use of synchrotron radiation to measure X-ray diffraction data. It does not form the same dimer motif observed in the 'three atom' chain compounds and has not formally formed a zwitterion; although there is evidence of proton sharing or disorder X-ray data are insufficient to create a disordered model, and the compound was modeled as formally neutral based on O-H and N-H distances. Room temperature analyses showed the proton transfer behavior to be independent of crystal temperature, and nuclear magnetic resonance studies show proton transfer behavior in solution. The formation of a zwitterionic hydrogen-bonded dimer is implicated in providing some stability during crystal growth of the easily crystallized 'three atom' chain compounds.