Formylation of Estrogens

Abstract

Reimer-Tiemann formylations of oestradiol and oestrone were investigated and, whilst substitution was effected under certain conditions to give mixtures of 2- and 4-formyloestrogens, yields were very low and the method was unsuitable for preparative purposes. Regioselective methods were developed and 2-formyloestradiol was conveniently prepared from oestradiol by formylation of the lithio derivative of the bis(methoxymethyl) ether and removal of the rotecting groups with hydrochloric acid. 4-Formyloestradiol was prepared by a sequence of reactions starting with the methoxyethyl ether of 4-bromooestradiol, then metal-halogen interconversion, formylation with N-methylformanilide, and removal of the protecting group. A number of related derivatives, including 2-formyloestriol, were prepared.