Green, one-pot strategy for substitution of the 5-position of 1,10-phenanthrolines

The preparation of symmetric 1,10-phenanthroline derivatives has been thoroughly explored, while substitution of the 5- or 6-positions on the phenanthroline backbone is less understood. Existing methods for forming these synthetic moieties (e.g., 5-nitro-1,10-phenanthroline) utilize highly toxic reagents and harsh conditions such as high temperatures and pressures. Curiously, alkylation at different phenanthroline positions affects both product formation rates and the products themselves. As a result, 5-substituted phenanthroline derivatives are often either expensive or unavailable commercially. A previously discovered breakthrough involves the formation of 1a,9b-dihydrooxireno[2,3-f][1,10]phenanthroline (epoxyphen). This synthetically expedient intermediate permits facile formation of 5-substituted derivatives of 1,10-phenanthroline and 2,9-dimethyl-1,10-phenanthroline upon treatment with strongly nucleophilic salts and solvation in methanol/water mixtures. Substitution with synthetically advantageous functional groups, such as nitrite, azide, benzenethiolate, imidazolate, cyanide, or arylsulfinates enables subsequent reactions to form carboxylic acids, primary amines, and reactive intermediates for click chemistry. These reactions proceed via an S_N2-like mechanism, in which ring-opening, driven by a loss of ring strain, precedes an elimination process that deprotonates the substituted phenanthroline carbon and eliminates the in situ-formed hydroxyl group. This mechanism results in moderate to good yields, facile purification, and high purity while replacing toxic reagents and energy-intensive conditions.