Quinone methide carbon

Quinone methides are the key intermediates in both resole resin syntheses and crosslinking reactions. They form by the dehydration of hydroxymethylphenols or dimethylether linkages (Fig. 7.24). Resonance forms for quinone methides include both quinoid and benzoid structures (Fig. 7.25). The oligomerization or crosslinking reaction proceeds by nucleophilic attack on the quinone methide carbon. 

One interesting property of quinone methide 63 is that the terminal carbon of the extended conjugated system lies in both an extended quinone methide (carbons marked by +) and an extended enol (carbons marked by ). This carbon reacts as both a base in undergoing protonation to form a quinone (upper pathway, Scheme 30A) and a Lewis acid in undergoing addition of nucleophilic... 

The quinone methide carbon of 71 is also the terminal carbon of an extended enol, and therefore reacts as both a nucleophile and electrophile (Scheme 32). This carbon shows a higher relative reactivity with electrophiles compared with nucleophiles than is observed for the corresponding terminal quinone carbon of mitomycins (Scheme 30A).73 Furthermore, the addition of nucleophiles to 71 is readily reversible, but the nucleophile adduct can be trapped by reoxidation to... 

This addition is general, extending to nitrogen, oxygen, carbon, and sulfur nucleophiles. This reactivity of the quinone methide (23) is appHed in the synthesis of a variety of stabili2ers for plastics. The presence of two tert-huty groups ortho to the hydroxyl group, is the stmctural feature responsible for the antioxidant activity that these molecules exhibit (see Antioxidants). 

The mechanism of this reaction has been studied by several groups [133,174-177]. The consensus is that interaction of ester with the phenolic resole leads to a quinone methide at relatively low temperature. The quinone methide then reacts rapidly leading to cure. Scheme 11 shows the mechanism that we believe is operative. This mechanism is also supported by the work of Lemon, Murray, and Conner. It is challenged by Pizzi et al. Murray has made the most complete study available in the literature [133]. Ester accelerators include cyclic esters (such as y-butyrolactone and propylene carbonate), aliphatic esters (especially methyl formate and triacetin), aromatic esters (phthalates) and phenolic-resin esters [178]. Carbamates give analogous results but may raise toxicity concerns not usually seen with esters. 

Uchida and Irie have reported a photochromic system based on ESIPT to an alkene carbon.82 They observed that vinylnaphthol 121 isomerizes to the ring-closed 123 when irradiated with 334 nm light ( = 0.20, Eq. 1.34). The reaction is photoreversible since irradiation of 123 (at400 nm) regenerates the starting vinylnaphthol. The authors proposed a mechanism in which ESIPT from the naphthol OH to the [3-alkenyl carbon gives intermediate o-quinone methide 122, which undergoes subsequent electrocyclic... 

Quinone Methides from ESIPT to Aromatic Carbon... 

The ability to photogenerate quinone methides via ESIPT from a phenol OH to an aromatic carbon atom was explored for a wider number of substrates by Wan s... 

A third reaction pathway for quinone methides generated following ESIPT to aromatic carbon (in addition to H-D exchange and cyclization) was observed following the examination of the photochemistry of 9-(2 -hydroxyphenyl)anthracene... 

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. 

Chiang, Y. Kresge, J. Zhu, Y. Flash photolytic generation and study of /j-quinone methide in aqueous solution. An estimate of rate and equilibrium constants for heterolysis of the carbon-bromine bond in p-hydroxybenzyl bromide. J. Am. Chem. Soc. 2002,124, 6349-6356. 

Amouri and coworkers also demonstrated that the nucleophilic reactivity of the exocyclic carbon of Cp Ir(T 4-QM) complex 24 could be utilized to form carbon -carbon bonds with electron-poor alkenes and alkynes serving as electrophiles or cycloaddition partners (Scheme 3.17).29 For example, when complex 24 was treated with the electron-poor methyl propynoate, a new o-quinone methide complex 28 was formed. The authors suggest that the reaction could be initiated by nucleophilic attack of the terminal carbon of the exocyclic methylene group on the terminal carbon of the alkyne, generating a zwitterionic oxo-dienyl intermediate, followed by proton transfer... 

These reactions clearly indicate that the exocyclic carbon of the complexed QM in these systems is nucleophilic in character, in contrast to its electrophilic nature in free o-quinone methides. The Cp Ir metal center stabilizes the mesomeric form in which the exocyclic carbon experiences high electron density (Scheme 3.18).29... 

To assess the trapping of biological nucleophiles, the pyrido[l,2-a]indole cyclopropyl quinone methide was generated in the presence of 5 -dGMP. The reaction afforded a mixture of phosphate adducts that could not be separated by reverse-phase chromatography (Fig. 7.16). The 13C-NMR spectrum of the purified mixture shown in Fig. 7.16 reveals that the pyrido [1,2-a] indole was the major product with trace amounts of azepino[l,2-a] indole present. Since the stereoelec-tronic effect favors either product, steric effects must dictate nucleophilic attack at the least hindered cyclopropane carbon to afford the pyrido[l,2-a]indole product. Both adducts were stable with elimination and aromatization not observed. In fact, the pyrido [1,2-a] indole precursor (structure shown in Scheme 7.14) to the pyrido [l,2-a]indole cyclopropyl quinone methide possesses cytotoxic and cytostatic properties not observed with the pyrrolo [1,2-a] indole precursor.47... 

SCHEME 7.23 Mechanism of quinone methide trapping of water with calculated 13C chemical shifts of the five-carbon center of methide enolates. 

Ralph, J. Ede, R. M. NMR of lignin model quinone methides. Corrected carbon-13 NMR assignments via carbon-proton correlation experiments. Holzforschung 1988,42,3 37-338. 

Combination of two Rb forms of coniferyl radicals (Fig. 5) gives rise to the transient double -quinone methide (III). Here nucleophilic attack on the y-carbon of the -quinone methide by the hydroxyl oxygen... 

Combination of an Ri, radical with an Ra radical yields the single p-qninone methide dimer (V). Here the quinone methide cannot become stabilized by an intramolecnlar addition reaction. Instead, nucleophilic attack of its y-carbon atom occurs by a hydroxyl ion from the medium, for example aromatization and protonation of the phenoxido ion thus formed give rise to guaiacylglycerol- 3-coniferyl ether (VI), again in racemic form dc-spite its two asymmetric carbon atoms. Since attack by the extraneous hydroxyl ion can occur on either side of C-y of the p-quinone methide (V), complete equilibration of the specific hydrogens from the original conifcryl alcohol moiety in the lower half of (V) presumably occurs (sec formulae on p. 131). 

Fig. 13.46). The initial addition to the p-alkenyl carbon gives a imine quinone methide 89. The latter rearomatizes upon addition of another water molecule to give dihydroxyl adduct 90. 

Further examination of the results indicated that by invocation of Pearson s Hard-Soft Acid-Base (HSAB) theory (57), the results are consistent with experimental observation. According to Pearson s theory, which has been generalized to include nucleophiles (bases) and electrophiles (acids), interactions between hard reactants are proposed to be dependent on coulombic attraction. The combination of soft reactants, however, is thought to be due to overlap of the lowest unoccupied molecular orbital (LUMO) of the electrophile and the highest occupied molecular orbital (HOMO) of the nucleophile, the so-called frontier molecular orbitals. It was found that, compared to all other positions in the quinone methide, the alpha carbon had the greatest LUMO electron density. It appears, therefore, that the frontier molecular orbital interactions are overriding the unfavorable coulombic conditions. This interpretation also supports the preferential reaction of the sulfhydryl ion over the hydroxide ion in kraft pulping. In comparison to the hydroxide ion, the sulfhydryl is relatively soft, and in Pearson s theory, soft reactants will bond preferentially to soft reactants, while hard acids will favorably combine with hard bases. Since the alpha position is the softest in the entire molecule, as evidenced by the LUMO density, the softer sulfhydryl ion would be more likely to attack this position than the hydroxide. 

Me2S+ group and the two CF3 groups in the adduct of the quinone methide. This more than balances the greater carbon affinity of the sulfur nucleophile expressed in the reaction with the /)-methoxybenzyl cation. 

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