Quinone methide intermediates

Scheme 10. Mechanislic possibililies for PF condensalion. Mechanism a involves an SN2-like attack of a phenolic ring on a methylol. This attack would be face-on. Such a mechanism is necessarily second-order. Mechanism b involves formation of a quinone methide intermediate and should be Hrst-order. The quinone methide should react with any nucleophile and should show ethers through both the phenolic and hydroxymethyl oxygens. Reaction c would not be likely in an alkaline solution and is probably illustrative of the mechanism for novolac condensation. The slow step should be formation of the benzyl carbocation. Therefore, this should be a first-order reaction also. Though carbocation formation responds to proton concentration, the effects of acidity will not usually be seen in the reaction kinetics in a given experiment because proton concentration will not vary.

In addition to methylene and dimethylether linkages, cured networks contain ethane and ethene linkages (Fig. 7.31). These side products are proposed to form through quinone methide intermediates. 

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

A number of carbonates and lactones have been shown to give rise to quinone methide intermediates on irradiation.90-92 For example, Padwa and coworkers92 demonstrated that 3-phenylisocoumaranone (146) will extrude a molecule of carbon monoxide when irradiated in methanol to generate ort/zo-quinone methide (24) with moderate efficiency ( = 0.058, Eq. 1.39). This intermediate is subsequently trapped by the methanol solvent to give 147. 

Van De Water, R. W. Pettus, T. R. R. cx-Quinone methides intermediates underdeveloped and underutilized in organic synthesis. Tetrahedron 2002, 58, 5367-5405. 

Diao, L. Yang, C. Wan, P. Quinone methide intermediates from the photolysis of hydroxybenzyl alcohols in aqueous solution. J. Am. Chem. Soc. 1995, 117, 5369-5370. 

Burnham, K. S. Schuster, G. B. A search for chiral photochromic optical triggers for liquid crystals photoracemization of l,l -binaphthylpyran through a transient biaryl quinone methide intermediate. J. Am. Chem. Soc. 1998, 120, 12619-12625. 

K. Mizutani, T. Electronic and structural requirements for metabolic activation of butylated hydroxytoluene analogs to their quinone methides, intermediates responsible for lung toxicity in mice. Biol. Pharm. Bull. 1997, 20, 571-573. (c) McCracken, P. G. Bolton, J. L. Thatcher, G. R. J. Covalent modification of proteins and peptides by the quinone methide from 2-rm-butyl-4,6-dimethylphenol selectivity and reactivity with respect to competitive hydration. J. Org. Chem. 1997, 62, 1820-1825. (d) Reed, M. Thompson, D. C. Immunochemical visualization and identification of rat liver proteins adducted by 2,6-di- m-butyl-4-methylphenol (BHT). Chem. Res. Toxicol. 1997, 10, 1109-1117. (e) Lewis, M. A. Yoerg, D. G. Bolton, J. L. Thompson, J. Alkylation of 2 -deoxynucleosides and DNA by quinone methides derived from 2,6-di- m-butyl-4-methylphenol. Chem. Res. Toxicol. 1996, 9, 1368-1374. 

From the synthetic investigations that have been described in the previous schemes, an appreciation of the mechanism for these reactions (methods A-H) has emerged in our group. However, the characteristics and exact nature of the o-quinone methide intermediate are still debated. Our past observations clearly indicate the cascade leading to the reactive species that behaves as an o-quinone methide should behave is... 

The generated quinone methide intermediates, during the disassembly, are highly reactive electrophiles and rapidly react with any available nucleophile (methanol or tetrabutylammonium hydroxide under organic solvent conditions). We could not isolate any significant amount of material that derived from the core molecule, probably due to generation of a mixture of compounds by the addition of different nucleophiles to the quinone methide. This molecule acts as an amplifier of a cleavage... 

FIGURE 7.24 Spectra obtained from spectral global fitting to the surface shown in Fig. 7.2 spectrum of quinone at zero time and the spectrum of the quinone methide intermediate. 

Zhou, Q. Pande, P. Johnson, A. E. Rokita, S. E. Sequence-specific delivery of a quinone methide intermediate to the major groove of DNA. Bioorg. Med. Chem. 2001, 9, 2347-2354. 

Landucci, L. L. Quinones in alkaline pulping. Characterization of an anthrahydroqui-none-quinone methide intermediate. Tappi 1980, 63, 95-99. 

Gierer, J. Ljunggren, S. The reactions of lignin during sulfate pulping. Part 17. Kinetic treatment of the formation and competing reactions of quinone methide intermediates. Sven. Papperstidn. 1979, 82, 503-512. 

Toikka, M. Sipila, J. Teleman, A. Brunow, G. Lignin-carbohydrate model compounds. Formation of lignin-methyl arabinoside and lignin-methyl galactoside benzyl ethers via quinone methide intermediates. J. Chem. Soc., Perkin Trans. 1998, 1, 3813-3818. 

Cyclobutane-fused pyrimidinones 39, precursors to quinone methide intermediates, have been prepared by reaction of amidines with the cyclopropane ester 38 <06EJOC2753>. 

Bertrand, F., et al., Skin sensitization to eugenol and isoeugenol in mice possible metabolic pathways involving ortho-Quinone and quinone methide intermediates. Chemical. Res. Toxicology, 10, 335, 1997. 

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