Reactions Of Quinone Methides Research Articles

Probing Molecular-Scale Oxidative Generation of Quinone Methides and Their Transformation Using Tip-Enhanced Raman Spectroscopy.

Quinone methides (QMs) are very important intermediates in chemistry. These species are most often generated in situ with metal oxidants and transition metal complexes. Here, tip-enhanced Raman spectroscopy (TERS) has been implemented to investigate the in situ oxidative generation of a QM species from alkylphenols facilitated by a transition metal complex. Using TERS, the metal oxidant-mediated transformation of a phenol species has been observed. The subsequent oxidative addition reaction of QM has also been identified based on distinct vibrational features, which have been assigned based on density functional theory (DFT). This study may establish TERS as a chemical detection tool for various QM-mediated reactions.

Photocyclization and Photoaddition Reactions of Arylphenols via Intermediate Quinone Methides.

A series of five benzannelated derivatives of 2-phenylphenol were prepared, and their photochemistry was investigated. Two of these (3-phenyl-2-naphthol, 10, and 1-phenyl-2-naphthol, 11) were photoinert. For 2-(1-naphthyl)phenol (12) and 1-(1-naphthyl)-2-naphthol (13), ESPT took place to either the 2'-position or the 7'-position of the naphthalene ring to give quinone methides (QMs) that underwent either reverse proton transfer (RPT) or electrocyclic ring closure to give dihydrobenzoxanthenes. The intermediate QMs for 12 and 13 were detected and characterized by laser flash photolysis. For 2-(9-phenanthryl)phenol (14), ESPT took place either to the 5'-position to give a QM that underwent quantitative electrocyclic ring closure to give the corresponding benzoxanthene or to the 10'-position to give a QM that underwent RPT. If the solution contained methanol, the QM produced on ESPT to the 10'-position in 14 could be trapped as the photoaddition product. The compounds studied in this work demonstrate three possible reactions of QMs produced following ESPT to aromatic carbon atoms: (1) reverse proton transfer (RPT) to regenerate starting material; (2) addition of hydroxylic solvents to give the photoaddition product; and (3) electrocyclic ring closure to give benzoxanthene derivatives.

ChemInform Abstract: Facile Synthesis of o‐ and p‐(1‐Trifluoromethyl)‐alkylated Phenols via Generation and Reaction of Quinone Methides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Facile Synthesis of o- and p-(1-Trifluoromethyl)-alkylated Phenols via Generation and Reaction of Quinone Methides

Several ortho- and para-(1-chloro-2,2,2-trifluoroethyl)phenols were prepared from the corresponding alcohols and thionyl chloride in the presence of pyridine. They reacted smoothly with sodium borohydride and Grignard reagents under mild conditions, forming 2,2,2-trifluoroethyl- or 1-trifluoromethylalkylphenols in high yields.

Influence of quinone methide reactivity on the alkylation of thiol and amino groups in proteins: studies utilizing amino acid and peptide models

Quinone methides (QMs) are electrophiles formed in several biological processes including direct oxidations of 4-alkylphenols by cytochromes P450. These species may be responsible for the adverse effects of certain phenolic compounds through protein alkylation, but little information is available concerning specific targets or the resulting mechanisms of cell injury. The present goal was to determine the most likely sites of adduct formation among competing protein nucleophiles utilizing QMs of varying electrophilicity. Reactions of poorly reactive, moderately reactive, and highly reactive QMs, 2,6-di-tert-butyl-4-methylene-2,5-cyclohexadienone (BHT-QM), 6-tert-butyl-2-(2′-hydroxy-1′,1′-dimethylethyl)-4-methylene-2,5-cyclohexadienone (BHTOH-QM), and 2-tert-butyl-6-methyl-4-methylene-2,5-cyclohexadienone (BDMP-QM), respectively, were investigated in aqueous solutions with nucleophilic amino acids. Each QM rapidly formed a thioether derivative of cysteine with little or no competition from the addition of water (hydration). The α-amino groups were the primary sites of alkylation for all other amino acids examined including lysine, histidine, tyrosine, and serine, and the pseudo-first order rates were 5 to 8-fold greater than the rates of hydration. Alkylation of the side chain nitrogens of lysine and histidine occurred at about one-fourth the rate of hydration for BDMP-QM, but no reaction was detectable for BHT-QM and no reactions occurred between QMs and amino acid hydroxyl groups. The results indicate that, based on chemical reactivity, peptide alkylation should occur in the order cysteine thiol>N-terminal amino>N ε-lysine=NIm-histidine, with side chain modifications occurring only with the more electrophilic QMs. Reactions of QMs with the tripeptide Gly-His-Lys confirmed the results with amino acids as N α-glycine alkylation predominated, but side chain adducts also formed with BHTOH-QM and BDMP-QM. Human hemoglobin was treated with QMs, hydrolyzed, and assayed by HPLC-thermospray mass spectrometry. This work revealed that N ε-lysine was the main alkylation site, emphasizing the importance of factors, in addition to chemical reactivity, which influence protein modification by electrophiles.

Conformational effects on the electronic structure and chemical reactivity of lignin modelp-quinone methides and benzyl cations

The electronic structure and its dependence on the conformation in typical lignin model intermediates, β-arylethericp-quinone methide {2-methoxy-4-[2-(2-methoxyphenoxy)]propylidene-2,5-cyclohexadien-1-one} and related benzyl cation has been determined on the basis of semi-empirical quantum chemical calculations. Electrostatic but not frontier orbital characteristics of lignin intermediates were demonstrated to be dependent on the conformation. Conformationally induced electrostatic non-equivalence of two possible routes of nucleophile approach to the reaction center may be the main cause of stereoselectivity of the reactions of quinone methides (but not related cations) with nucleophiles. Quinone methides and related cations also differ in their intramolecular charge transfer properties.

Reaction of quinone methides with proteins: Analysis of myoglobin adduct formation by electrospray mass spectrometry

Reaction of quinone methides with proteins: Analysis of myoglobin adduct formation by electrospray mass spectrometry

A novel approach to 4-benzylisoouinolines

The reaction of quinone methides with 3.4-dihydroisoquinoline or isoquinoline leads to benzylisoquinoline derivatives. NMR and ms investigations as well as chemical degradation prove that benzylation takes place at C-4 of the isoquinoline nucleus. Spectroscopic data are given for all new compounds.

Mass Spectra of Quinonemethide Products Derived from Reaction with Phenolics, Anthrone and Anthrahydroquinone

Abstract Several experiments have been performed to show the effects of anthrahydroquinone (AHQ), the reduced form of anthraquinone (AQ), on the self-condensation reactions of simple lignin models. These experiments were aimed at understanding the role of AQ as a wood pulping catalyst. The experiments led to some very complex product mixtures. A detailed analysis of the product mixtures by gas chromatography - mass spectrometry (GC/MS) was undertaken in order to understand how AHQ retarded phenolic-quinonemethide condensation reactions. The interpretation of the mass spectra is reported here. Two principal classes of compounds are discussed: phenolic condensation products and adducts derived from the reactions of quinonemethides with AHQ and anthrone. A method of volatilizing the sample prior to GC/MS analysis, namely derivatization with dimethyl sulfate In alkaline THF, produces by-products which contain incorporated THF.