The kinetics and mechanisms of additions to olefinic substances. Part 15. Chlorination of cholest-5-ene and its 3-substituted derivatives, including cholest-5-en-3-one; factors affecting the α : β ratio for electrophilic attack, and for product formation, in cholest-5-enes

Abstract

Reactions of cholest-5-ene or its 3β-substituted derivatives with chlorine in chloroform or chlorobenzene give as kinetically controlled products the expected 5α,5β-dichloride, accompanied by the isomeric 5β,6α-dichloride as a minor component. The proportion of the latter decreases with the electron-withdrawing power of the 3β-substituent. Neither added pyridine nor added chloride ion affects the product proportions significantly. Cholest-5-en-3-one, on the other hand, when treated with chlorine in chlorobenzene containing 2-methyloxiran gives not only the expected 5α,6β-dichloride but also much 6α- and 6β-chlorocholest-4-en-3-one. Comparison with the results for 4β-deuteriocholest-5-ene shows that the formation of 6α-chlorocholest-4-en-3-one involves mainly displacement of the 4β-hydrogen atom, and that the formation of its 6β-isomer involves mainly but not exclusively displacement of the 4β-hydrogen atom. Similar products are obtained in deuteriochloroform containing pyridine; in acetic acid, substitution is accompanied by little addition and much unidentified material The results are compared with the corresponding results for bromination, epoxidation, and iodination. It is argued that halogenation of cholest-5-en-3-one differs from that of cholest-5-ene and its 3-monosubstituted derivatives in the ratio of attack on the α- and β-faces of the molecule for two main reasons: because of the availability of a concerted pathway for substitution involving the chair conformation of ring A of the enone, and because in non-concerted pathways for addition and substitution, ring A of the intermediate halogenonium ion derived from the enone can reach a boat conformation. Two types of Ad_E3 additions having different stereochemical preferences can also be recognised.