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Quinone methides in the photodehydration of 2-hydroxy-3-(hydroxymethyl)anthracenes

Quinone methides (QMs) are important intermediates in the photochemistry of phenols. Interest in their chemistry was initiated by the discovery of their biological activity ; they are potent DNA alkylating and cross-linking agents. The most common photoreaction for the formation of QMs is photodehydration of hydroxymethyl-substituted phenols.[1] Further, Popik et al. have reported on photodehydration of 2-naphthol derivatives giving rise to QMs. The suggested photochemical reaction mechanism involved ESIPT in 1 as a primary step, followed by the formation of benzoxete 2 and ring-opening to QM 3 (Eq. 1) [2]. Later, we investigated a series of 2-hydroxy-2-adamantyl derivatives of naphthols wherein photodehydration and formation of QMs was also documented. However, benzoxete derivatives were not detected. In addition, we conducted an antiproliferative investigation of the photogenerated QMs and found that the adamantyl derivative of 2-naphthol gives QMs with the selective activity on MCF-7 carcinoma cells.[3] Herein, we report the photodehydration of a series of anthrols. Although anthracene derivatives are important QM precursors in some clinical anticancer drugs, the photodehydration reaction of anthrols has not been reported. The photodehydration reaction in the anthrol series is envisaged to be of particular importance in the potential development of novel anticancer treatments based on the photogeneration of QMs as a potential DNA-alkylating species. We investigated the photodehydration reaction mechanism in the anthracene series by preparative irradiations, fluorescence measurements, and laser flash photolysis (LFP). For example, the LFP measurements for anthrol 4 in trifluoroethanol (TFE) gave rise to the transient spectra that was assigned to QM 5. Contrary to the results of Popik in the naphthalene series, no evidence was found for formation of a benzoxete. QM 5 decays by protonation giving cation 6 that subsequently reacts with nucleophiles giving stable adducts 7 (Eq. 2).

Anthrols; Anthracene derivatives; Photodehydration; Quinone methides

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