Useful examples for discussion of proton-NMR spectroscopy: N-substituted alpha-aminobenzenebutanenitriles

Headnote

Useful Examples for Discussion of Proton-NMR Spectroscopy: N-Substituted alpha-Aminobenzenebutanenitriles

Anisotropy of Diastereotopic Methylene Protons

John Almy,* R. Martinez Alvarez,** A. Herrera Fernandez, and A. Sanchez Vazquez

Departamento de Quimica Organica I, Facultad de Ciencias Quimicas, Universidad Complutense, E-28040, Madrid, Spain

Undergraduate texts commonly discuss the anisochrony (non-coincidence of NMR signals) of methylene protons near chiral centers using projections in which the chiral center and the carbon bearing the methylene protons are separated by a single bond. Specialized texts (1-3) treat this in more depth and with examples. Analysis of the rotational conformers about this bond demonstrates the nonequality of the protons in question and emphasizes the fact that the chemical shift for a given proton is the weighted average for the proton in its various conformations. These projections are helpful, but in many cases the carbon bearing diastereotopic protons and the chiral center are separated by more than one bond.

During characterization of alpha-(methylamino)benzenebutanenitrile (1), which has two consecutive methylene groups attached to its chiral center, we were surprised to observe that although both pairs of methylene protons are diastereotopic and therefore technically anisochronous, only the y protons actually displayed different chemical shifts. The P protons, which are separated from the chiral center by fewer bonds, gave no measurable chemical shift difference.

We report here a summary of the study we made to explore this phenomenon.

Data

N-Substituted derivatives of the alpha-aminobenzenebutanenitrile system (1-5) and alpha-methylaminopropanenitrile (6, Table 1) are obtained by easy one-step syntheses.

Our interest was focused on the chemical shift differences (Delta delta^sup Upsilon Upsilon'^ and Delta delta^sub beta beta'^) for the diastereotopic protons of the two methylene groups. The chemical shifts and apparent geminal coupling constants could be measured directly from the spectra and/or best fit analyses of the signal shapes using RACCOON software and double resonance experiments. In Table 2 are listed the anisochronies found within the methylene protons of 1-6 in various solvents. Anisochronies of over 0.03 ppm were first estimated by locating the AB subspectra (4) within the signals representing thebeta and/or Upsilon protons. The initial value for Delta delta ^sub Upsilon Upsilon'^ and Delta delta &^sub beta beta'^ was then tested and adjusted by simulation with RACCOON software using typical values for the geminal (-12 to...