NMR Determination of Hydrogen Bond Thermodynamics in a Simple Diamide: A Physical Chemistry Experiment

Variable temperature NMR spectroscopy is used to determine the Δ H ° and Δ S ° of hydrogen bond formation in a simple diamide. In this two- or three-day experiment, students synthesize N, N ′-dimethylmalonamide, dimethylsuccinamide, dimethylglutaramide, or dimethyladipamide from methylamine and the corresponding diester (typically in 50% recrystallized yield) and record NMR spectra at temperatures between 200 and 313 K. Solutions of N -methylacetamide in concentrations between 1.00 mM and 13.1 M (neat) are prepared and their NMR spectra recorded to determine the chemical shift of the amide proton in the hydrogen-bonded (δ B ) and nonbonded (δ N ) limits. By using these data, the equilibrium constants, Δ H °, and Δ S ° for the conversion of an open-chain diamide to a cyclic structure with an intramolecular hydrogen bond are determined.