Acid- and Base-Catalyzed Isomerization of Androst-5-ene-3,17-dione and 17α-Ethynyl-17β-hydroxy-5-estren-3-one

Article abstract of DOI:10.1021/jo01302a013

Isomerization of androst-5-ene-3,17-dione (1) to androst-4-ene-3,17-dione (2) and of 17α-ethynyl-17β-hydroxy-5-estren-3-one (3) to 17α-ethynyl-17β-hydroxy-4-estren-3-one (4) is kinetically general acid-base catalyzed; 1 is more reactive than 3.Deuterium solvent kinetic isotope effects, k(H2O)/k(D2O), of ca.6 for tertiary amine catalyzed isomerization indicate rate-determining protonation of dienolate ions.The greater reactivity of 1 than 3, catalyzed by tertiary amines, is probably due to a greater concentration of the 1 dienolate ion than of the 3 dienolate ion.Ethanolamine, but not tris(hydroxymethyl)aminomethane, catalyzes isomerization of 1 and 3 via Schiff-base formation.Curvilinear pseudo-first-order plots for isomerization of 1 and 3 catalyzed by DCl/D2O indicate that partitioning of dienols is kinetically important.