Side chain entropy and the activation of organocobalamins for carbon-cobalt bond homolysis: Synthesis, characterization, and thermolysis of the neopentyl derivative of a unique cobalamin analog lacking a c side chain

Hydrodeamination of the c-amino derivative, 5, of cyanocobalamin (CNCbl) with hydroxylamine-O-sulfonic acid in aqueous base leads to an extensively rearranged product instead of the c side chain truncated derivative, 1, expected from simple deamination. The rearranged product (CNCbl-8-butanamide) crystallizes in the orthorhombic system, space group P2(1)2(1)2(1) with unit cell dimensions a = 16.041(11), b = 21.94(2), and c = 25.43(2) Angstrom. It is devoid of substituents at corrin ring C(7) but quaternized at C(8) with an ''upwardly'' pseudoaxial methyl group and a d side chain expanded by one methylene group to a butanamide. The corrin ring of this rearranged derivative is significantly flatter (corrin ring fold angle 9.9 degrees) than CNCbl itself (fold angle 18.0 degrees). Conversion of CNCbl-8-butanamide to its neopentyl derivative (NpCbl-8-butanamide), a NpCbl analog which lacks a c acetamide side chain, permits a quantitative assessment of the influence of thermal motions of the c side chain on the entropy of activation for carbon-cobalt bond thermal homolysis in NpCbl. NpCbl-8-butanamide is shown to thermolyze homolytically to give products derived from the Np-. radical quantitatively. The kinetics of the thermolysis of NpCbl-8-butanamide were studied in aerobic aqueous solution at temperatures between 15 and 45 degrees C. After correction of the observed first-order rate constants for the presence of the essentially unreactive base-off species using an established NMR method, an Eyring plot yields the activation parameters Delta H-on(double dagger) = 26.7 +/- 0.1 kcal mol(-1) and Delta S-on(double dagger) = 13.2 +/- 0.2 cal mol(-1) K-1. While the enthalpy of activation is slightly reduced (6%) from that of NpCbl, the entropy of activation is reduced by 6.1 +/- 0.6 cal mol(-1) K-1, or 32 +/- 3%. The c side chain thus contributes about one-third of the total entropic activation of NpCbl for carbon-cobalt bond homolysis, and the entropy of activation for this reaction is probably dominated by changes in the thermal motions of the ''upwardly'' pseudoaxial a and c acetamide side chains as the reaction progresses.