Studies on vitamin d and related compounds. XVIII: An investigation into the interconversion of precalciferol and calciferol and of analogous compounds

Two simple calciferol analogues (1) having no five‐membered (D) ring fused to the C ring, show the same smooth thermal isomerisation to the corresponding precalciferol analogues as calciferol itself. The kinetics of this reaction have been studied; the activation energy and entropy were found to be 21.6 (± 0.2) kcal/mole and −17.2 e.u., respectively. The insensitivity of the reaction towards even rather drastic changes in the conditions is striking and the reaction mechanism formerly given 10, 15 for the vitamin D ⇆ previtamin D interconversion seems to remain an attractive working hypothesis. There is one difference between the analogues and the calciferol system itself; in the former the equilibrium is far more on the “precalciferol” side. It is argued that this difference (and perhaps also the relative long wavelength ultra‐violet absorption of precalciferol) may be due to a strain in the precalciferol molecule originating from the presence of the C 8 ‐C 9 double bond in combination with the trans fused five‐membered ring. In agreement herewith, 13α‐precalciferol analogues having the five‐membered ring cis ‐bonded and lacking this strain, are found to show a position of the equilibrium (and an ultra‐violet absorption) similar to that of the analogue II and different from that of precalciferol.