SECONDARY KINETIC ISOTOPE EFFECTS IN C-N ROTATION OF AMIDES

A secondary deuterium kinetic isotope effect (KIE) k(H)/k(D) of 2.0 was recently reported for trans --> cis isomerization of 1-phenylcyclohexene-2-d. The large value was attributed to loss of all the zero-point energy associated with the out-of-plane C-H bending mode. If this phenomenon is general, a large KIE might also be manifested in the C-N rotation of amides, whose rates can be determined by NMR methods. To demonstrate KIEs convincingly, it is necessary to measure the rates for H and D amides simultaneously in the same solution. Such measurements are possible because isotope shifts separate the signals. The kinetics of stereoisomerization were followed by line-shape analysis, saturation transfer, or selective inversion recovery. For HCONHD k(H)/k(D) is only 1.16 +/- 0.10, and for DCON(CH3)2 it is only 1.18 +/- 0.04. For HCONDCH3 k(H)/k(D) is 1.00 +/- 0.03, which is equivalent to no isotope effect at all. For HCONDC6H4NO2-p k(H)/k(D) is 1.04 +/- 0.03, which is quite small. The absence of any KIE in HCONDCH3 could be confirmed by H-1 NMR. We therefore conclude that there is no large secondary KIE for C-N rotation in amides, for substitution at carbon or at nitrogen. The absence of any large effect is discussed in terms of the bending modes of reactant and transition state. The KIE in HCONH2 may arise from thermal population of excited vibrational states.