Synthesis of Symmetrical Disubstituted Bridgehead Adamantane Derivatives

The symmetric bridge disubstituted adamantane derivatives are the key raw materials or intermediates for preparing multisubstituted adamantane derivatives with admantane as the core. With 1-adamantane carboxylic acid that is more efficient and economical as an initial reactant, a series of synthesis technologies of symmetrical disubstituted bridgehead adamantane derivatives which have significant applications, were studied in this work. Those synthesis technologies include the following: 1,3-adamantane dicarboxylic acid (1) was synthesized by 1-adamantane carboxylic acid through Koch-Haaf carbonylation; compound 1 was reduced to get 1,3-adamantane dimethanol(2); compound 2 reacted by bromination in HBr-ZnBr2 system to afford 1,3-dibromomethyl adamantane(3). Meanwhile, compound 2 converted to 1, 3-dichloromethyl adamantane (4) through Apple-Lee reaction. The structures of prepared products were confirmed by IR spectra and H-1 NMR spectroscopy. The possible reaction mechanism was proposed, and the synthesis conditions were discussed and optimized for each technology respectively.