The POXs can decompose in the presence of a base as shown in . The reaction generates a negatively charged OP analogue and the conjugate acid of the base used, which is highly unfavorable from an energetic standpoint. Thermodynamic calculation were carried out using either water or ethoxide ion as a base, which yielded the reaction enthalpies for the decomposition pathway of about 160 kcal/mol and −55 kcal/mol respectively. These seemingly contradictory energetics for the decomposition process are consistent with the proton affinities of each nucleophile, water and ethoxide, respectively. Thus proton transfer to the OP analogue will take place simultaneously to the generation of the conjugate acid. Therefore, we hypothesize that the decomposition process occurs via a proton-shuttle mechanism as shown in and the corresponding reaction enthalpies are summarized in .
Hypothesized decomposition pathway for POXs via proton-shuttle mechanism.
All of the decomposition processes were found to be exothermic overall, confirming that decomposition is a thermodynamically viable pathway for POX species. Based on the decomposition enthalpies, 3-POXs were found to be more favorable toward the decomposition pathway. This result is supported by the fact that 2- and 4-POXs are resonance stabilized but 3-POXs are not. The exothermicities of the decomposition process were nearly doubled in the aqueous phase, because two molecules were solvated on the product side which yielded higher solvation energy compared to the parent POX at the reactant side. This was confirmed by comparing the gas phase and the solution phase energies.
By comparing the energetics among the sets of POXs, we found that 2-POXs were 3–5 kcal/mol less stable than 3- and 4-POXs. This could be explained by the steric bulk provided by the pyridinium methyl group around the oxime-OP linkage, which is not present in the case of 3-POXs and 4-POXs. This observation was also supported by previous work2
which showed that 3- and 4-POXs were 100–500 times more stable than the 2-POXs. Additionally, we performed CHELPG charge analysis for all of the POX species to gain insight into the parameters governing the decomposition pathway of the POXs (.) The trends in the charges were similar to the thermochemical results: charge separation at the O–N bond was about 3–5 fold higher in the 2-POXs than the others, indicating a higher propensity for decomposition, and thus lower stability. In addition, the benzylic proton had the highest positive charge concentration in the case of 2-PAM, which correlates with the increased propensity for decomposition in 2-POXs.
CHELPG charges (in units of electrons) at the B3LYP/6-311+G**//B3LYP/6-31+G* level in the aqueous phase for the POXs. (Atom labels are shown in .)