Studies on the Oxidation of Aromatic Steroids

by Manning, Terence David

This thesis is concerned primarily with a study of the oxidation of aromatic steroids employing either chromium trioxide-aqueous acetic acid or chromium trioxide-aqueous sulphuric acid-acetone mixtures. The nature of the chromic acid oxidation of various functional groups is discussed first and this is followed by an outline of the two methods used for the synthesis of the aromatic steroids which were oxidised in this study. The second part of the discussion deals with the oxidation of these aromatic steroids.

It was found that chromic acid oxidation of ring-A aromatic steroids containing a strong electron-donating C3-substituent, such as methoxyl, gave the corresponding 9-hydroxy-11-oxo derivative (ketol). However, a ketol was not formed if a C3-methoxyl substituted ring-A aromatic steroid also contained a substituent at C1.

When a C3-methoxyl substituent was present, the 6-oxo-ring-A aromatic steroid was a minor oxidation product but such compounds were the major products from the chromic acid oxidation of ring-A aromatic steroids containing a weak C3-electron-donating group, such as acetoxyl. The oxidation of a ring-A aromatic steroid containing a C2-methoxyl substituent gave an almost quantitative yield of the corresponding 6-oxo compound.

Suzuki103 has claimed that the major oxidation product of 17?-acetoxy-3-methoxyestra-1,3,5(10)-triene (34b) is 17 ?-acetoxy-9?- hydroxy-3-methoxyestra-1,3,5(10)-trien-11-one (123). Physical and chemical evidence are presented to show that this product is in fact the 9?-hydroxy epimer and a reaction pathway for its formation is proposed.

An examination of the oxidation products of a ring-B aromatic steroid and a ring-C aromatic steroid shows that no ketols were formed.