N-Alkyl-N-methylacetamidinium Ions. Isomerization and Water Catalyzed Exchange Rates in D2O

We found that the sigmoided-type profile of kobs. vs. pD plot, fits the rate expression : kobs = (k1[D ] + k2Ka)/ (Ka + [D ]), where k1 and k2 are the rates of isomerization of the acetamidinium ion and the acetamidine respectively and Ka is the acidity equilibrium constant of the acetamidinium ion. These constants were evaluated by measuring the rates at each pD using dynamic NMR(H) (line shape analysis and saturation transfer). Based on the low barrier of 19.7 Kcal/mol at 25C (k1 = 0.02 s ) it was suggested that the isomerization (EZ-ZE) of the acetamidinium form procceds throw rotation of the C-N partial double bond. We argued that this relatively low barrier is due the steric repulsion of the N-benzyl group that destabilizes the ground state (planar amidinium) relative to its twisted transition state. On the other hand, our result supports that the E-syn-Z-anti isomerization of the acetamidine form proceeds via rotation about a C-N single bond as it had been proposed previously. We stated that the proposed mechanism was in agreement with the measured low barrier of 14.7 Kcal/mol at 25C (k1= 126 s). In order to test the proposed mechanisms and in view of the biological importance of the acetamidines we have undertaken a systematic study on the isomerization of N -alkyl-Nmethylacetamidines as a complementary support to our previous results on the N-benzyl.N methylacetamidine. Therefore we have prepared the following acetamidines: N-allyl-N C N