Relationships between the acidity of the Z and E isomers of N ‐Nitroso‐ N ‐alkyl‐α‐amino acids and their conformations

The acidity constants of both Z and E conformational isomers of five N ‐nitroso‐ N ‐alkyl‐α‐amino acids, ONN(R 1 )CH(R 2 )COOH, are determined by the observation of selected pH titrated 1 H NMR signals. For two glycine derivatives (1, R 1 CH 3 , R 2 H, ONSar; 2, R 1 C 2 H 5 , R 2 H, ONEtGly) and two alanine derivatives (3, R 1 CH 3 , R 2 CH 3 , ONMeAla; 4, R 1 C 2 H 5 , R 2 CH 3 , ONEtAla) the E isomers appear to be stronger acids than the Z while for the third alanine derivative (5, R 1 n ‐C 3 H 7 , R 2 CH 3 , ONPrAla) the opposite is observed. These results, also including anisotropy effects associated with the NNO group, are discussed in terms of conformations. A 7‐membered ring conformation with an NO…HOOC intramolecular hydrogen bond is proposed to be statistically important in the Z isomers of 1, 2, 3 and, to a lesser extent, 4.