Stable three-center hydrogen bonding in a partially rigidified structure.

The three-center hydrogen bond in diaryl amide 1 was examined by IR and 1H NMR spectroscopy, X-ray crystallography, and ab initio calculations. By comparing 1 with its structural isomers 2, 3 and 4, and with its conformational isomers 1a-c, it was found that the two two-center components of the three-center interaction reinforce each other, that is, the enhanced stability of the three-center hydrogen bond is a result of positive cooperativity between the two components. Substituents not involved in hydrogen bonding have little effect on the strength of the two- and three-center hydrogen bonds. To our knowledge, this is the first three-center hydrogen-bonding system that has been shown to exhibit positive cooperativity. Ab initio calculations of the geometries, vibrational modes, and 1H NMR chemical shifts also support the experimental findings. These results have provided a new insight into the three-center intramolecular hydrogen bonding in a partially rigidified structure and have provided a reliable motif for designing stably folded structures.