Para-Quinone methide

The mechanisms for model condensation reactions of para-hydroxymethyl-substituted phenol (and therefore para-quinone methide) with reactive ortho positions are described in Fig. 7.29. The phenolate derivatives react with para-quinone... 

Figure 7.28 Preferential formation of para-quinone methides.

Para-quinone methide intermediates, 403 Para-quinone methides, 404 para-Trishydroxybenzylamine, reaction with 2,4-xylenol, 397 Partial aromatic polyamides, 136, 143, 180-184... 

Much attention has been devoted to the development of methods to generate quinone methides photochemically,1,19-20 since this provides temporal and spatial control over their formation (and subsequent reaction). In addition, the ability to photogenerate quinone methides enables their study using time-resolved absorption techniques (such as nanosecond laser flash photolysis (LFP)).21 This chapter covers the most important methods for the photogeneration of ortho-, meta-, and para-quinone methides. In addition, spectral and reactivity data are discussed for quinone methides that are characterized by LFP. 

Rabin, O. Vigalok, A. Milstein, D. Metal-mediated generation, stabilization, and controlled release of a biologically relevant, simple para-quinone methide BHT-QM. 

The enzyme vanillyl-alcohol oxidase (VAO, E.C. 1.1.3.38) was examined in detail with respect to mechanism, structural properties, and biotechnological applications by van Berkel and coworkers, giving an excellent example of how detailed biochemical studies provide a basis for preparative biocatalytic applications (for recent reviews see[1, 21). The homooctamer with a monomer mass of 65 kDa was isolated and purified from Penicillium simplicissimum. The catalytic mechanism of VAO-catalyzed oxidation of para-alkyl phenols was studied in detail[3-5 After initial hydride abstraction from the Ca atom, a binary complex of the intermediate para-quinone methide and reduced FAD reacts with molecular oxygen, regenerating the... 

The reaction mechanism is quite similar to the one of VAO and also includes an intermediate, the para-quinone methide. Like VAO, 4-cresol-oxidoreductase also exhibits a high enantioselectivity for (S)-l-(4 -hydroxyphenyl)alkylalcohols1591. 

Failure was met with when the formation of the dibenzoxepine ring of cula-rines was attempted by generating an electron-deficient system like that of ortho-quinones or para-quinone methides in ring C of an 8-hydroxybenzylisoquinoline 66). Finally, acid treatment of benzylisoquinoline 95 66) gives benzofuran 96, which is related to the quettamine class of alkaloids 67). 

Formal a-diarylmethylation of malonates was achieved through the development of a 1,6-selective conjugate addition-aromatization sequence with para-quinone methides as vinylogous electrophiles (Scheme 4) [8]. The driving force toward aromatization would make nucleophilic addition to the 8-position more thermodynamically favorable than addition to the p-position. Under solid-liquid biphasic conditions, the A-spiro chiral ammonium salt 5 appeared to be the most active and selective promoter. The electronic character of the aryl ester substituents on the malonate was linked to the stereochemical outcome, and introduction of a para-halophenyl group led to a significant decrease in the enantioselectivity. Based... 

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. 

The absence of methylol (-CH2OH) groups in all six lower molecular weight resorcinol-formaldehyde condensates which have been isolated [119] reflects the high reactivity of resorcinol under acid or alkaline conditions. It also shows the instability of its para-hydroxybenzyl alcohol groups and their rapid conversion to jpara-hydroxybenzyl carbonium ions or quinone methides. This explains how identical condensation products are obtained under acid or alkaline reaction conditions [119]. In acid reaction conditions methylene ether-linked condensates are also formed, but they are highly unstable and decompose to form stable methylene links in 0.25 to 1 h at ambient temperature [121,122]. 

The oxidation by strains of Pseudomonas putida of the methyl group in arenes containing a hydroxyl group in the para position is, however, carried out by a different mechanism. The initial step is dehydrogenation to a quinone methide followed by hydration (hydroxylation) to the benzyl alcohol (Hopper 1976) (Figure 3.7). The reaction with 4-ethylphenol is partially stereospecific (Mclntire et al. 1984), and the enzymes that catalyze the first two steps are flavocytochromes (Mclntire et al. 1985). The role of formal hydroxylation in the degradation of azaarenes is discussed in the section on oxidoreductases (hydroxylases). 

In a similar approach, double deprotonation of r 6-coordinated ortho- and para-cresols, 30 and 31, with t-BuOK led to formation of stable r 4-coordinated p- and o-quinone methide complexes of manganese, 32 and 33 (Scheme 3.19).37... 

Iverson, S. L. Hu, L. Q. Vukomanovic, V. Bolton, J. L. The influence of the para-alkyl substituent on the isomerization of o-quinones to p-quinone methides potential hioac-tivation mechanism for catechols. Chem. Res. Toxicol. 1995, 8, 537-544. 

Benzyl(a)-aryl ether linkages are cleaved by alkali if there is a free phenolic hydroxyl group para to the propyl side chain or an adjacent hydroxyl in the p-position (JO). Quinone methide intermediates are involved in the former hydrolysis and epoxides in the latter. 

In phenols with ortho or para unsaturated side chains, coupling reactions may occur outside the aryl ring, and may form new carbon-carbon or carbon-oxygen bonds. Benzylic radicals may also be generated, perhaps by hydrogen atom abstraction, and lead to coupling at this position. Finally the products arising from quinones, quinone ketals, or quinone methides may dominate. 

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