Synthesis of 1,2- and 2,4-Disubstituted Adamantanes. The Protoadamantane Route

A number of 1,2-disubstituted adamantanes have been prepared easily by using the facile rearrangement of 4-substituted protoadamantanes as the synthetic principle. The conversion of 4-methylprotoadamantan-4-ol (3) to the 1-methyladamantane 2-substituted alcohol 4, bromide 5, acetamide6, amine 7, and ketone 8 are high-yield processes. The reaction of 4-protoadamantanone (2) with PCL₃-PCL₅ afforded 4-chloroprotoadamantene (10) as well as the 1,2-dichloroadamantane (11) rearrangement product. The dichloride (11) was also prepared by reaction of thionyl chloride on adamantane-l,2-diol (13). In addition, the Ritter reaction on adamanto[2,1-d]oxazolidin-2-one (1) gave 1-N-acetyladamantane-1,2-diamine hydrochloride (14) and its hydrolysis product, adamantane-1,2-diamine dihydrochloride (15). 2,4-Disubstituted adamantanes can also be prepared via protoadamantane precursors. Starting from protoadamantene (19), epoxidation followed by acid hydrolysis afforded adamantane-2a,4a-diol (27). Bromination of protoadamantene (19) gave a 2:1 ratio of 2a,4a-dibromoadamantane (23) and 2e,4a-dibromoadamantane (25).