Conformation and Configuration of Tertiary Amines via GIAO-Derived ¹³C NMR Chemical Shifts and a Multiple Independent Variable Regression Analysis

The ¹³C chemical shifts of six tertiary amines of unambiguous conformational structure are compared to predicted ¹³C NMR chemical shifts obtained via empirically scaled GIAO shieldings for geometries from MM3 molecular mechanics calculations. An average deviation, |Δδ|_av, of 0.8 ppm and a maximum deviation, |Δδ|_max, of 2.8 ppm between predicted and experimental ¹³C shifts of the six tertiary amines of unambiguous structure are found. In several cases of tertiary amines subject to rapid exchange, where experimental ¹³C shifts at room temperature are weighted averages of multiple conformers, a comparison of calculated ¹³C shifts of all reasonable MM3 predicted conformers with experimental ¹³C shifts via a multiple independent variable regression analysis provides an efficient method of determining the major and minor conformers. The examples presented are 2-methyl-2-azabicyclo[2.2.1]heptane and 1,6-diazabicyclo[4.3.1]decane, which each have two expected contributing structures, and 2-(diethylamino)propane and 1,8-diazabicyclo[6.3.1]dodecane, where ten and seven low-energy conformers, respectively, are predicted by MM3 calculations.