Side Chain Entropy and Activation of Organocobalamins for Thermal Homolysis: Thermolysis of Neopentyl-13-epi- and Neopentyl-8-epicobalamin in Neutral Aqueous Solution

A complete product and kinetic analysis has been carried out for the thermolysis of neopentyl-8-epicobalamin (Np-8-epiCbl) and neopentyl-13-epicobalamin (Np-13-epiCbl), epimers of neopentylcobalamin, NpCbl, in which the orientation of the d or e propionamide side chain has been altered by epimerization at corrin ring C8 or C13, respectively. When the organic products of the aerobic thermolysis of Np-8-epiCbl or Np- 13-epiCbl are treated with aniline in diethyl ether, the Schiff's base of pivalaldehyde is formed with a yield of approximately 50%. This observation is consistent with the disproportionation of the neopentyl peroxide radical to pivalaldehyde and neopentyl alcohol under aerobic thermolysis conditions. Anaerobic thermolysis in neutral aqueous solution in the presence of (4-hydroxy-2,2,6,6-tetramethylpiperidinyl)oxy, H-TEMPO, gives rise to quantitative yields of the 0-alkylated neopentyl-H-TEMPO and 8- or 13-epicob(II)alamin. Moreover, examination of the anaerobic thermolysis of these complexes in the presence of 0.5-1.0 mM H-TEMPO showed that the rate constants for thermolysis are the same as those obtained in neutral aerobic solution, establishing that dissolved oxygen is a competent trap for the homolytically derived radicals. These results clearly reveal that the mode of thermal C-Co cleavage is homolytic as is known to be the case for NpCbl itself. Thermolysis kinetics were studied in aerobic, neutral aqueous solution spectrophotometrically and gave the following observed activation parameters: Np-8-epiCbl, @obs = 28.7 f 0.1 kcal mol-' and APobs 17.1 f 0.2 cal mo1-l K-'; Np-13-epiCb1, o Np-13-epiCb1, @on = 29.7 f 0.2 kcal mol-' and APon = 24.0 f 0.6 cal mol-' K-l. Comparison of these values with the currently accepted values for base-on NpCbl in aqueous solution (Man = 28.3 f 0.2 kcal mol-' and APon = 19.3 f 0.6 cal mol-' K-l) shows that the enthalpy of activation for C-Co bond homolysis is essentially unchanged by side chain epimerization (@on = 28.7 f 0.5 kcal mol-') but that the entropy of activation is increased by 4.7 f 0.8 cal mol-' K-' by epimerization at C13 and by 3.1 f 0.9 cal mol-' K-' by epimerization at C8. These results are discussed in terms of the importance of side chain thermal motions in determining the entropy difference between the ground and the transition states of NpCbl for its thermal homolysis.