Ab InitioQuantum-Mechanical Study of the Stability of Cyclic α-Acetoxy-N-nitrosamines:  Amine N→NO Dative Bonding in α-Hydroxy-N-nitrosaminesversusN→Carbocation Dative Bonding inN-Nitrosiminium Ions

Abstract

The dissociations of R-hydroxy-N-nitrosopyrrolidine, 1, and R-hydroxy-N-nitrosopiperidine, 2, to form the nitrosiminium ions, 3 and 4, respectively, have been studied as models for the S N 1 process of the corresponding R-acetoxy-N-nitrosamines. In excellent agreement with experiments, the ionization of the pyrrolidine derivative is found to be more endothermic at ab initio levels up to MP4(SDTQ)/6-31G*//RHF/ 6-31G* and including corrections for thermal motions. This finding is explained with more efficient NfNO π-dative bonding in 1 compared to 2 while ring size effects in 3 and 4 are rather small. The activation barriers to NN-rotation provide quantitative measures of the strengths of the NfNO π-dative bonding in 1-4 and the transition-state structures 1-TS-4-TS for the rotation about the NN bonds in 1-4 were determined. Electron density analyses (NBO) and electrostatic field analysis (CHELPG, MKS) were performed to assess the extent of NfNO π-dative bonding in R-hydroxy-N-nitrosamines and the electronic relaxation associated with the competition between amine NfNO and Nfcarbocation π-dative bonding in N-nitrosiminium ions. The comparative analysis of the structural and electronic relaxation associated with ionization in the presence (1-4) or absence (1-TS-4-TS) of the possibility for NfNO π-dative bonding demonstrate in a compelling fashion that σ-polarizations are responsible for most of the electron density relaxation.

Cyclic α-Acetoxynitrosamines: Mechanisms of Decomposition and Stability of α-Hydroxynitrosamine and Nitrosiminium Ion Reactive Intermediates

“…High level ab initio calculations on a very similar system, detailed in the accompanying paper, are qualitatively consistent with the experimental observations made here. In the reactions below, calculations at the MP4(SDTQ)/6-31G*//RHF/6-31G* level indicate that the equilibrium for the six-membered ring system in eq 12 is favored over the five-membered ring system in eq 13 by 7.96 kcal/mol.…”

“…The differences in equilibrium and rate constants are inconsistent with a claim made previously that the five-member ring cation is more stable than the six-member ring cation. 16 High level ab initio calculations on a very similar system, detailed in the accompanying paper, 29 are qualitatively consistent with the experimental observations made here. In the reactions below, calculations at the MP4(SDTQ)/6-31G*//RHF/6-31G* level indicate that the equilibrium for the six-membered ring system in eq 12 is favored over the five-membered ring system 1.…”

“…13 For the R-hydroxynitrosamines, the greater reactivity of the pyrrolidine compared to the piperidine can be speculated upon in light of the ab initio computations presented in the accompanying paper. 29 As described earlier, these calculations indicate a larger interaction between the amino nitrogen and the nitroso group in the case of the pyrrolidine compared to the piperidine compound. It is ultimately the ability of the nitroso group to accept electron density that makes the nitrosamino group a relatively good nucleofuge compared to the amine anion.…”

“…Thus, this increased electron density on the amino nitrogen in the case of R-acetoxy-N-nitrosopiperidine engenders a greater driving force for expulsion of the acetate ion leaving group (k 1 , eq 8) and, in the reverse reaction, a greater stability of the iminium ion from the piperidine derivative because the product of the k -1 step (eq 8) is not so strongly stabilized by electron delocalization into the nitroso group. 29 r-Hydroxynitrosamines. As before, 13 these compounds were generated by reduction using tributylphosphine in acetonitrile and were subsequently subjected to kinetic study by mixing in a stopped flow spectrophotometer with a 25-fold excess of aqueous solution.…”

“…It is reasonable that the same is true in the case of the α-acetoxynitrosamines. Thus, this increased electron density on the amino nitrogen in the case of α-acetoxy- N -nitrosopiperidine engenders a greater driving force for expulsion of the acetate ion leaving group ( k 1 , eq 8) and, in the reverse reaction, a greater stability of the iminium ion from the piperidine derivative because the product of the k - 1 step (eq 8) is not so strongly stabilized by electron delocalization into the nitroso group …”