Quinone methide oxygen

O-Alkylation and O-protonation of the quinone methide oxygen effect on intrinsic reaction barriers 75... 

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). 

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.

Di Valentin, C. Freccero, M. Zanaletti, C. Sarzi-Amade, M. o-Quinone methide as alkylating agent of nitrogen, oxygen, and sulfur nucleophiles. The role of H-bonding and solvent effects on the reactivity through a DFT computational study, j. Am. Chem. Soc. 2001, 123, 8366-8377. 

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... 

The JACS paper describes the total synthesis of the more highly oxygenated (-)-tetracycline 16. To this end, the alcohol S was carried on to the enone 10. Opening of the cyclobutane 11 to the o-quinone methide followed by Diels-Alder cycloaddition to 10 delivered the endo adduct 12. 

Effects of oxygen substitutents in an aromatic ring upon an exocyclic rather than endocyclic carbocation charge center have also been measured. The possibility of comparing HO, MeO, and O substituent effects for the benzylic cations is provided by recent studies of quinone methides, including the unsubstituted / -quinone methide 23, which may be considered as a resonance-stabilized benzylic cation with a /xoxyanion substituent. 

It seems clear therefore that more reactive cations than those for which Ritchie s N+ relationship was developed, show a distinct dependence of selectivity between nucleophiles upon the stability and reactivity of the carbocation. Richard has confirmed that for a very stable benzylic carbocation, represented by the bis-trifluoromethyl quinone methide 57, the N+ regime is restored and that a plot of log k against N+ for reactions of nucleophiles, including amines, oxygen and sulfur anions, the azide ion, and a-effect nucleophiles, shows a good correlation with N+.219... 

Generation of quinone methides by unmasking a quinone oxygen 57... 

Quinone methides are strikingly different from the 1,2- and 1,4-isomers, because there is no direct orbital interaction between the meta-oxygen and carbon substituents at the benzene ring. Consequently, the neutral valence bond resonance form for the 1,3-quinone methide is a triplet biradical (Scheme 1). These 1,3-quinone methides are chemically more unstable and difficult to generate than their 1,2- and 1,4-isomers, which exist as stable neutral molecules.8... 

Yates and coworkers have examined the mechanism for photohydration of o-OH-8. The addition of strong acid causes an increase in the rate of quenching of the photochemically excited state of o-OH-8, and in the rate of hydration of o-OH-8 to form l-(o-hydroxyphenyl)ethanol. This provides evidence that quenching by acid is due to protonation of the singlet excited state o-OH-8 to form the quinone methide 9, which then undergoes rapid addition of water.22 Fig. 1 shows that the quantum yields for the photochemical hydration of p-hydroxystyrene (closed circles) and o-hydroxystyrene (open circles) are similar for reactions in acidic solution, but the quantum yield for hydration of o-hydroxystyrene levels off to a pH-independent value at around pH 3, where the yield for hydration of p-hydroxystyrene continues to decrease.25 The quantum yield for the photochemical reaction of o-hydroxystyrene remains pH-independent until pH pAa of 10 for the phenol oxygen, and the photochemical efficiency of the reaction then decreases, as the concentration of the phenol decreases at pH > pAa = 10.25 These data provide strong evidence that the o-hydroxyl substituent of substrate participates directly in the protonation of the alkene double bond of o-OH-8 (kiso, Scheme 7), in a process that has been named excited state intramolecular proton transfer (ESIPT).26... 

The o-quinone methide 41 was generated by cleavage of (2-hydroxybenzyl)-trimethylammonium iodide (H-41-N(Me3)NOT DEFINED+1-) in hot aqueous solution. The products of trapping of 41 by oxygen, sulfur, and nitrogen nucleophile were characterized.75... 

The silyl group is widely used as an oxygen protecting group, because of the ease of its removal by nucleophilic substitution by fluoride anion. The protected phenols 0-(tert-butyldimethylsilyl)-/ -(bromomethyl)phenol (45) and 0-(tert-butyldimethylsilyl)-2,6-bis(bromomethyl)phenol (46) react rapidly with fluoride anion in water to form the corresponding phenols, which then break down to the ortho-quinone methide 41 (Scheme 21A) and the substituted ortho-quinone... 

Antitumor agents mitomycin A (61 A) and mitomycin C (61C) contain a latent quinone functionality, which is exposed by reductive activation and elimination of a glycoside or an alcohol followed by opening of the aziridine ring. These quinone methides then react with nucleic acids to form bis-adducts.103 The reductive activation of mitomycins provides selectivity in targeting solid tumors, because this is favored in the oxygen-deprived environment of tumor cells, and inhibited by the oxygen-rich environment of healthy tissues.107... 

The kinetic barriers to organic reactions depend on both the thermodynamic driving force to the reaction (Fig. 3A) and the intrinsic barrier (A, Fig. 3B) to the reaction in the absence of any driving force (Ag° = 0).148 149 The effect of alkylation of the quinone oxygen of quinone methide p-1 and of alkylation of a... 

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