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 intra-molecular hydrogen bonding in a partially rigidified structure and have provided a reliable motif for designing stably folded structures.