Effects of backbone rigidification on intramolecular hydrogen bonding in a family of diamides

In an effort to gain insight on the balance of noncovalent forces that controls the adoption of folded conformations in small molecules, we have examined intramolecular hydrogen bond formation in a series of diamides containing a variety of conformational constraints. The intramolecularly hydrogen-binded state of flexible diamide 2 was previously shown to be enthalpy favored by about 1.5 kcal/mol relative to the non-hydrogen-bonded state in methylene chloride. For flexible diamide 1, however, the enthalpic preference for the intramolecularly hydrogen-bonded state is only about 0.4 kcal/mol in this solvent