D 2 O‐catalyzed proton transfer selectivity of 4 different NH protons in the same molecule

When N ‐benzyl‐ N′ ‐methylacetamidinium hydrochloride (pKa=11.8) is dissolved in D 2 O/DCl(1 M), an equilibrium of 2 54:46 stereoisomers in an ~2:1 =(R)N δ + H(D) D/H ratio is formed. Therefore, 2 R =N‐benzyl ( E and Z ) and 2 R = N ‐methyl (E and Z) groups attached to the corresponding H(D) ( Z and E ) for a total of 8 1 H‐NMR signals are observed. Consequently, their rates of H and D transfer to D 2 O can be measured by means of the 1 H‐NMR broadness (line shape) of the =( R )N δ + H doublets and =( R )N δ + D broad singlets. Acidity selectivity is observed for both processes. In fact, the relative proton and deuterium transfer rates follow the acidity order: =(PhCH 2 )N δ + ‐H( E ) > =(PhCH 2 )N δ + ‐H( Z ) > =(Me)N δ + ‐H( E ) > =(Me)N δ + ‐H( Z ). Proton transfer rates are in the range of 8 to 0.5 s ‐1 with α = .92. This tendency is independently supported by the observed experimental chemical shift deuterium isotopic perturbation. The rate‐limiting step for proton exchange is the breaking of the hydrogen bond due to the fast amidine reprotonation (~10 11 s). =(R)N δ + D/=(R)N δ + H equilibration is reached at ~80 s, and it can be measured by the relative =( R) N δ + H versus =( R) N δ + D signal integrations. The equilibrium of the 4 =(R)N δ + H(D) centers is shifted toward deuterium, but they are further shifted in the more basic centers. Equilibrium is completely shifted toward D in the 4 centers when OD − contributes with the exchange process at pD > 3.