Comparative Study of Photochemically Generated Conjugated Ortho- and Para-Quinone Methide Reactivity

Isomeric ortho- and para-quinone methides, while possessing similar electronic structures, show very different properties. o-Quinone methides (oQM) are more reactive towards nucleophiles and undergo very fast and efficient inverse electron-demand-Diels-Alder (IEDDA) reaction with electron-rich alkenes. p-Quinone methide, while also acting as Michael acceptors, is not reactive in IEDDA.

The photochemical generation of o-naphthoquinone methide (o-NQM) from (3-hydroxynaphthalen-2-yl)methanol (o-NQMP) derivatives can be achieved with UV-A light  This reaction has been employed for the development of photolabile protecting groups (PPGs), procedure for the protein and peptide labeling, as well as reversible surface derivatization.    

In the present project, (3-hydroxynaphthalen-2-yl)(4-hydroxyphenyl)methanol (QMP 1) was designed to explore the feasibility of a novel approach to the generation of a  fluorescent dye. Interestingly, photo-dehydration of QMP 1 can produce both tautomers: o-naphthoquinone methide (o-NQM 1) and p-quinone methide (p-QM 1). Thus, the photoreactivity study of QMP 1 was carried to find out the predominant form of QM. Comparative analysis of the kinetics of QMP 1 reactions versus two structural analogs QMP 2, and QMP 3 will be presented. Photo-dehydration of QMP 2 can only form o-naphthoquinone methide analog (o-NQM 2), while QMP 3 is expected to produce only p-quinone methide analog (p-QM 3). Furthermore, applications of QMP analogs as fluorophores for imaging techniques will be provided.

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