Sterically Congested Adamantylnaphthalene Quinone Methides

Five new (2-adamantyl)­naphthol derivatives (5–9, quinone methide precursors, QMP) were synthesized
and their photochemical reactivity was investigated by preparative
photolyses, fluorescence spectroscopy, and laser flash photolysis
(LFP). Excitation of QMP 5 to S1 leads to
efficient excited state intramolecular proton transfer (ESIPT) coupled
with dehydration, giving quinone methide QM5 which was
characterized by LFP (in CH3CN–H2O, λmax = 370 nm, τ = 0.19 ms). On irradiation of QMP
5 in CH3OH–H2O (4:1), the quantum
yield of methanolysis is Φ = 0.70. Excitation
of naphthols QMP 6–8 to S1 in CH3CN leads to photoionization and formation of naphthoxyl
radicals. In a protic solvent, QMP 6–8 undergo solvent-assisted PT giving QM6 or zwitterion QM8 that react with nucleophiles delivering adducts, but with
a significantly lower quantum efficiency. QMP 9 in a
protic solvent undergoes two competitive processes, photosolvolysis
via QM9 and solvent-assisted PT to carbon atom of the
naphthalene giving zwitterion. QM9 has been characterized
by LFP (in CH3CN–H2O, λmax > 600 nm, τ = 0.9 ms). In addition to photogenerated QMs,
two stable naphthalene QMs, QM10 and QM11 were synthesized thermally and characterized by X-ray crystallography. QM10 and QM11 do not react with H2O but undergo acid-catalyzed fragmentation or rearrangement. Antiproliferative
activity of 5–9 was investigated
on three human cancer cell lines. Exposure of MCF-7 cells treated
with 5 to 300 nm irradiation leads to an enhanced antiproliferative
effect, in accordance with the activity being due to the formation
of QM5.