The photochemical generation of several novel quinone methide-type intermediates has been observed upon photolysis of pyridoxine (150-Vitamin B₆) and its derivatives 151 and 152, hydroxybiphenyl alkenes 153 and 154, and hydroxybiphenyl alcohols 159 and 160. Mechanistic investigations, utilizing product, fluorescence and laser flash photolysis studies, have suggested two distinct pathways for the formation of these reactive intermediates, depending upon the functional groups present on the progenitor. Formal excited state intramolecular proton transfer (ESIPT) between the phenol and the alkene led to quinone methides upon irradiation of the hydroxybiphenyl alkenes, while excited state proton transfer (ESPT) to solvent followed by dehydroxylation was responsible for formation of these intermediates from the hydroxybiphenyl alcohols. The quinone methide-type intermediates obtained from the pyridoxine systems arise from formal loss of water, although it is not certain whether this is through ESIPT or ESPT from the phenol at neutral pH.
Studies of the photogeneration of quinone methide-type intermediates from the pyridoxine systems are important due to their biological relevance. Formation of such reactive intermediates in vivo may explain some of the toxicological properties associated with the intake of large doses of the vitamin.
Irradiation of 150 or 151 in 1:1 CH₃OH/H₂O gave the corresponding methyl ethers (Φp = 0.18 and 0.21, respectively), consistent with formation of quinone methide-type intermediates. Similarly, photolysis in aqueous CH₃CN with ethyl vinyl ether resulted in the regioselective formation of the respective chroman products through [4+2] cycloaddition. LFP spectra pointed to formation of two quinone methide-type intermediates upon irradiation of both 151 and 152 in neutral aqueous solution, only one of which is present at pH 12.
Previous studies on m-hydroxystyrene have suggested that m-quinone methide formation occurs via formal ESIPT between the phenol and the alkene, mediated by a bridging water trimer. Studies on 153 and 154 were undertaken to determine whether this solvent-mediated ESIPT can occur over longer distances. The photochemistry of the related hydroxybiphenyl alcohols (159 and 160) was also investigated, as quinone methides have been observed upon photolysis of similar systems.
Irradiation of 153 and 154 in 1:1 CH₃CN/H₂O gave photohydration products (Φp =
0.013 and 0.1, respectively) via attack of water on the respective quinone methides. pH
studies implicated formal ESEPT in formation of these reactive intermediates. Photolysis of
the analogous methyl ethers of the phenols suggested the intermediacy of carbocations in the
observed photohydration reaction, as quinone methides cannot be generated in these systems.
Hydroxybiphenyl alcohols 159 and 160 yielded the corresponding photomethanolysis
products (Φp = 0.04 and 0.22) in aqueous methanol, through attack of CH₃OH on the
respective quinone methides. In this case, pH studies indicated that quinone methide
formation occurs via ESPT and dehydroxylation.
Significant quenching of fluorescence firom the hydroxybiphenyl alkenes with small
amounts of added water implied that H₂O is directly involved in reaction from the singlet
excited state. Loss of fluorescence firom 154 was found to depend on [H₂O ]³, however, the
distance required for ESIPT in these systems is too large to be bridged by a water trimer. As
such, the non-linear quenching has been attributed to deprotonation of the phenol by a cluster
of one or two water molecules, with concerted protonation at the alkene by another molecule
of water not associated with the cluster. Fluorescence quenching of the hydroxybiphenyl
alcohols required much larger [H₂O], and implied a different mechanism of reaction,
consistent with the proposal of ESPT and dehydroxylation.
LFP studies indicated the assistance of water is required for formation of a long-lived
transient (600 nm, t = 150 μs) upon irradiation of 153, however, it cannot be definitively
assigned to the quinone methide. Although no evidence was found for quinone methide
formation in LFP studies of 154 and 160 due to its suspected short lifetime, the respective
carbocation (420 nm, t =8.5 μs) has been observed upon irradiation in 2,2,2-trifluoroethanol. / Graduate
| Identifer | oai:union.ndltd.org:uvic.ca/oai:dspace.library.uvic.ca:1828/9414 |
| Date | 30 May 2018 |
| Creators | Brousmiche, Darryl Wayne |
| Contributors | Wan, Peter |
| Source Sets | University of Victoria |
| Language | English, English |
| Detected Language | English |
| Type | Thesis |
| Format | application/pdf |
| Rights | Available to the World Wide Web |
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