Quinone methide, formation from

Foster, K. L. Baker, S. Brousmiche, D. W. Wan, P. o-Quinone methide formation from excited state intramolecular proton transfer (ESIPT) in an o-hydroxystyrene. J. Photochem. Photobiol. A Chem. 1999, 129, 157-163. 

Thompson DC, Perera K, London R. Quinone methide formation from para isomers of methylphenol (cresol), ethylphenol, and isopropylphenol relationship to toxicity. Chem Res Toxicol 1995 8 55-60. 

Bolton, J. L. Comeau, E. Vukomanovic, V. The influence of 4-alkyl substituents on the formation and reactivity of 2-methoxy-quinone methides evidence that extended ji-conjugation dramatically stabilizes the quinone methide formed from eugenol. Chem.-Biol. Interact. 1995, 95, 279-290. 

Fig. 7. Formation of an j/2-o-quinone methide complex from an aldol condensation of crotonaldehyde and the j/2-phenol complex 85.

A two-electron oxidation of N-acetyltyrosine ethyl ester with mushroom tyrosinase, or with periodate, afforded the N-acetyIdopa ester 142, together with the (Z)-enamide 145 and the 6-acetoxydopa amide 146 (Fig. 40) (284). It is assumed that 145 originates from dopaquinone 143 via 144 by tautomerization. Michael addition of acetate to quinone 143 is believed to be the origin of 146. The formation of quinone methide 144 from dopa ester 142 by tyrosinase is reminiscent of the formation of iminochromes and quinone methides catalyzed by this enzyme in their formation from a-methyl dopa ester (285), and such reactions may well occur in mammalian systems. 

Quinone methides are frequently reported as intermediates from irradiation of arenes having a methyl or substituted methyl group in the 2-position to a carbonyl or nitro group (H-abstraction) or a hydroxy function (formal loss of water). The latter process has been studied with pyridoxine (201) and its derivatives (202) and (203), and the mechanism by which the loss occurs is found to depend upon the pH of the solution. In neutral solution, the formation of the quinone methide (204) from (201) arises either by excited state proton transfer to the aqueous methanol solvent and loss of OH from the phenoxide ion, or by intramolecular proton transfer and loss of water, while the reaction in alkaline solution involves dehydroxylation from the excited state of the phenoxide ion. 

Attwood M R, Brown B R, Lisseter S G, Torrero C L, Weaver P M 1984 Spectral evidence for the formation of quinone-methide intermediates from 5- and 7-hydroxyflavonoids. J Chem Soc Chem Commun 177-179... 

In addition to the above possible mechanisms the possibility of reaction at w-positions should not be excluded. For example, it has been shown by Koebner that o- and p-cresols, ostensibly difunctional, can, under certain conditions, react with formaldehyde to give insoluble and infusible resins. Furthermore, Megson has shown that 2,4,6-trimethylphenol, in which the two ortho- and the one para-positions are blocked, can condense with formaldehyde under strongly acidic conditions. It is of interest to note that Redfam produced an infusible resin from 3,4,5,-trimethylphenol under alkaline conditions. Here the two m- and the p-positions were blocked and this experimental observation provides supplementary evidence that additional functionalities are developed during reaction, for example in the formation of quinone methides. 

Wan s group showed that the observed photodehydration of hydroxybenzyl alcohols can be extended to several other chromophores as well, giving rise to many new types of quinone methides. For example, he has shown that a variety of biphenyl quinone methides can be photogenerated from the appropriate biaryl hydroxybenzyl alcohols.32,33 Isomeric biaryls 27-29 each have the benzylic moiety on the ring that does not contain the phenol, yet all were found to efficiently give rise to the corresponding quinone methides (30-32) (Eqs. [1.4—1.6]). Quinone methides 31 and 32 were detected via LFP and showed absorption maxima of 570 and 525 nm, respectively (in 100% water, Table 1.2). Quinone methide 30 was too short lived to be detected by LFP, but was implicated by formation of product 33 that would arise from electrocyclic ring closure of 30 (Eq. 1.4). 

Stokes, S. M. J. Ding, F. Smith, R L. Keane, J. M. Kopach, M. E. Jervis, R. Sabat, M. Harman, W. D. Formation of o-quinone methides from T 2-coordinated phenols and their controlled release from a transition metal to generate chromans. Organometallics 2003,22, 4170-4171. 

The third primary intermediate in the oxidation chemistry of a-tocopherol, and the central species in this chapter, is the orr/zo-quinone methide 3. In contrast to the other two primary intermediates 2 and 4, it can be formed by quite different ways (Fig. 6.4), which already might be taken as an indication of the importance of this intermediate in vitamin E chemistry. o-QM 3 is formed, as mentioned above, from chromanoxylium cation 4 by proton loss at C-5a, or by a further single-electron oxidation step from radical 2 with concomitant proton loss from C-5a. Its most prominent and most frequently employed formation way is the direct generation from a-tocopherol by two-electron oxidation in inert media. Although in aqueous or protic media, initial... 

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