Reactive intermediate, oxidation mechanism

As shown in equation 12, the chemistry of this developer s oxidation and decomposition has been found to be less simple than first envisioned. One oxidation product, tetramethyl succinic acid (18), is not found under normal circumstances. Instead, the products are the a-hydroxyacid (20) and the a-ketoacid (22). When silver bromide is the oxidant, only the two-electron oxidation and hydrolysis occur to give (20). When silver chloride is the oxidant, a four-electron oxidation can occur to give (22). In model experiments the hydroxyacid was not converted to the keto acid. Therefore, it seemed that the two-electron intermediate triketone hydrate (19) in the presence of a stronger oxidant would reduce more silver, possibly involving a species such as (21) as a likely reactive intermediate. This mechanism was verified experimentally, using a controlled, constant electrochemical potential. At potentials like that of silver chloride, four electrons were used at lower potentials only two were used (104). 

There is some debate in the literature as to the actual mechanism of the Beirut reaction. It is not clear which of the electrophilic nitrogens of BFO is the site of nucleophilic attack or if the reactive species is the dinitroso compound 10. In the case of the unsubstituted benzofurazan oxide (R = H), the product is the same regardless of which nitrogen undergoes the initial condensation step. When R 7 H, the nucleophilic addition step determines the structure of the product and, in fact, isomeric mixtures of quinoxaline-1,4-dioxides are often observed. One report suggests that N-3 of the more stable tautomer is the site of nucleophilic attack in accord with observed reaction products. However, a later study concludes that the product distribution can be best rationalized by invoking the ortho-dinitrosobenzene form 10 as the reactive intermediate. 

Cu(IIl) is believed to be one of the reactive intermediates in a chain mechanism. Both Cu(III) and As(IV) are invoked in discussion of the oxidation of As(III) by Cu(II)-S208 which also displays chain character. Two sets of kinetic results have been published. Those of Woods et indicate the general reac-... 

An in situ infrared investigation has been conducted of the reduction of NO by CH4 over Co-ZSM-5. In the presence of O2, NO2 is formed via the oxidation of NO. Adsorbed NO2 then reacts with CH4. Nitrile species are observed and found to react very rapidly with NO2, and at a somewhat slower rate with NO and O2. The dynamics of the disappearance of CN species suggests that they are reactive intermediates, and that N2 and CO2 are produced by the reaction of CN species with NO2. While isocyanate species are also observed, these species are associated with A1 atoms in the zeolite lattice and do not act as reaction intermediates. A mechanism for NO reduction is proposed that explains why O2 facilitates the reduction of NO by CH4, and why NO facilitates the oxidation of CH4 by O2. 

Although this mechanism could explain the inertness of di-t-butyl sulphide towards oxidation due to the absence of a-hydrogen atoms, it was later ruled out by Tezuka and coworkers They found that diphenyl sulphoxide was also formed when diphenyl sulphide was photolyzed in the presence of oxygen in methylene chloride or in benzene as a solvent. This implies that a-hydrogen is not necessary for the formation of the sulphoxide. It was proposed that a possible reactive intermediate arising from the excited complex 64 would be either a singlet oxygen, a pair of superoxide anion radical and the cation radical of sulphide 68 or zwitterionic and/or biradical species such as 69 or 70 (equation 35). 

Irreversible adsorption The LH mechanisms assume that the adsorption of all gas-phase species is in equilibrium. Some mechanisms, however, occur by irreversible steps. In these cases, the intermediates are again treated in the same manner as reactive intermediates in homogeneous mechanisms. An example is the Mars-van Krevelen (1954) mechanism for oxidation, illustrated by the following two steps ... 

HO2, was considered as a reactive intermediate in both cases. The addition of radical scavengers strongly retarded the oxidation of the phosphinate ion confirming the radical type mechanism. It was also demonstrated that the reaction ceased when the catalyst was masked with EDTA. 

Nearly all of the microbial and mammalian transformation studies with this group of alkaloids have been focused on nicotine. Microorganisms have been used to resolve racemic nicotine to make available unnatural (/ )-(+)-nicotine for biological evaluation. Highly significant work has detailed the mechanism of nicotine oxidation in mammals, and has resulted in the identification of reactive intermediates formed as the alkaloid is transformed by hepatic monooxygenases. The chemistry and pharmacology of the pyridine alkaloids is discussed by Strunz and Findlay in Volume 26 of this treatise. 

In contrast to this mechanism, the one proposed in our work operates direct from the oxidation state of the alkane feedstock. The same alkyl cation intermediate can lead to both alkane isomerization (an alkyl cation is widely accepted as the reactive intermediate in these reactions) and we have shown in this paper that a mechanistically viable dehydrocyclization route is feasible starting with the identical cation. Furthermore, the relative calculated barrier for each of the above processes is in accord with the experimental finding of Davis, i.e. that isomerization of a pure alkane feedstock, n-octane, with a dual function catalyst (carbocation intermediate) leads to an equilibration with isooctanes at a faster rate than the dehydrocyclization reaction of these octane isomers (8). 

Some authors have expressed concerns that bulk accumulation of reactive intermediates (and thus chemical capacitance) violates electroneutrality. ° However, it should be recalled that reduction (or oxidation) of a material not only involves depletion (or accumulation) of oxygen ions in the bulk but neutral combinations of oxygen ions and compensating electrons/holes which together may accumulate without violating electroneutrality. Indeed, no other mechanisms have yet been proposed which satisfac-... 

Chemical capacitance. When the mechanism involves significant involvement of the bulk, accumulation of reactive intermediates not only involves surface species but oxidation and reduction of the bulk. This can be detected as an anomalously high effective capacitance, often referred to as a chemical (or pseudo) capacitance. This capacitance can be as large as 0.1 — 1 F/cm and thus easily detected by current-interruption or impedance techniques. Thus, capacitance is a strong indicator (independent of resistance) as to what degree the interface, surface, and/or bulk are playing in the... 

In addition to the assessment of reversible inhibition, the role played by mechanism-based inhibitors (irreversible inhibitors) provides a focus during lead development, as it can result in a more profound and prolonged effect than that suggested by the therapeutic dose or exposure. Mechanism-based inhibition (MBI) occurs as a result of the CYP generating reactive intermediates that bind to the enzyme causing irreversible loss of activity. Oxidative metabolism via that CYP is only restored upon re-synthesis of that enzyme. Three mechanisms have been reported showing how intermediate species act as mechanism-based inhibitors ... 

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