HAT hydrogen atom

Shorthand notations such as ET (electron transfer), HAT (hydrogen atom transfer), BDE (bond dissociation energy), NHE (normal hydrogen electrode), CV (cyclic voltammetry), LFP (laser flash photolysis), EPR (electron paramagnetic resonance) and KIE (kinetic isotope effect) will be used throughout the chapter. In addition, recurring chemical compounds such as TEMPO (2,2,6,6-tetramethylpiperidine-Ai-oxyl), HBT (1-hydroxyben-zotriazole), BTNO (benzotriazole-A-oxyl), HPI (iV-hydroxyphthalimide), PINO (phthal-imide-iV-oxyl), NHA (A-hydroxyacetanilide) and a few others will be referred to by means of the capital-letter acronym. 

In vitro tests, used in evaluation of antioxidant properties make use of the ability of antioxidants to quench free radicals. Based on this mechanism, the methods are divided into two groups SET - single electron transfer, and HAT - hydrogen atom transfer. Reactions with antioxidants in assays with the DPPH radical, ABTS and the Folin-Ciocalteu reagent both operate according to the SET and HAT mechanism. Due to the kinetics of the reaction, they are included in the... 

In the HAT mechanism, a hydrogen atom is transferred from the -carbon of the amine to FAD to form a carbinyl radical and FADH semiquinone radical. FADH semiquinone radical abstracts the unpaired electron from the carbinyl radical forming the imine and FADH2 after protonation. 

FIGURE 4.51 Mechanism for cytochrome P450-catalyzed N-dealkylation via an initial single electron pathway, SET, or via the hydrogen atom abstraction pathway, HAT. 

The O-dealkylation of ethers, while not as frequently encountered as N-dealkylation in drug metabolism studies, is still a common metabolic pathway. Mechanistically it is less controversial than N-dealkylation in that it is generally believed to proceed by the HAT pathway, i.e., a-hydrogen atom abstraction followed by hydroxyl radical rebound, and not a SET pathway (Fig. 4.58). The product of the reaction is unstable, being a hemiacetal or hemiketal depending on the number of hydrogens on the a-carbon, which dissociates to generate an alcohol and an aldehyde or ketone. 

Besides this hydrogen atom transfer (HAT) route, the aminoxyl radical may also take part in oxidation procedures where, through a preliminary monoelectronic step, it is converted into an oxoammonium ion (R2N=0+), or variations of this route. Examples of... 

SCHEME 7. The hydrogen atom transfer (HAT) pathway of an aminoxyl radical... 

Inhibition mechanisms by A/-cyclopropyl MPTP analogues are also discussed in terms of two catalytic pathways, one of which is based on an initial SET step from the nitrogen lone pair, as proposed by Silverman, and the second is based on an initial a-carbon hydrogen atom transfer (HAT) step, as proposed by Edmondson, leading to a radical and dihydropyridinium product formation. The observation that MAO B catalyzes the efficient oxidation of certain 1-cyclopropyl-4-substituted-1,2,3,6-tetrahydropyridines to the corresponding dihydropyridinium metabolites suggests that the catalytic pathway for these cyclic tertiary allylamines may not proceed via the putative SET-generated aminyl radical cations [122], Further studies will be necessary to clarify all the facets of the mechanism of inhibition of MAO by cyclopropylamines. 

MONOBASIC. Descriptive of acids having one displaceable hydrogen atom per molecule. Acids hat ing two. three, or more displaceable hydrogen atoms arc called dibasic, tribasic. and polybasic. respectively,... 

Nitroxyl radicals have also been used extensively in mechanistic studies of hydrogen atom transfer (HAT), development of catalytic oxidation reactions,109 and for pharmacological purposes.110 Some of the recent examples include HAT from... 

Instead, it is the goal of this chapter to highlight some conceptually novel developments in the field of HAT reactions. We will concentrate on complexes of borane with N-heterocyclic carbenes (NHCs), on organometallic hydrogen atom donors in stoichiometric and catalytic reactions, and on the activation of water and alcohols for HAT. 

While these reactions are of limited use in the synthesis of complex molecules, they are very interesting from a mechanistic point of view. It has been firmly established that benzylic or allylic radicals and metal centered radicals are formed as intermediates through hydrogen atom transfer from the M-H bond to the C-C double bond. Interestingly, the addition of the hydrogen atom is reversible as demonstrated by isotope scrambling with deuterated olefins. If the radicals possess multiple sites for hydrogen atom abstraction, olefin isomerization can ultimately occur. HAT to unactivated olefins was not observed. 

Polymerization reactions of suitably substituted acrylates can be initiated by radical generation through HAT [27]. It should be noted that hydrogen atom abstraction from the growing chain leads to interruption of chain growth. In such cases the organometallic complex possessing the pivotal M-H bond is reformed and... 

Hydrogen atoms bonded to carbons aren t shown. Since carbon always hat a valence of 4, we mentally supply the correct number of hydrogen atoms for each carbon. 

Another mechanistic ambiguity which has attracted considerable interest is the possible intermediacy of radical cations in the oxidative functionalization of alky-laromatic substrates with different organic and inorganic oxidants, a process involving C-H bond cleavage which can occur in a single step by direct hydrogen-atom transfer (HAT) from the neutral substrate to the oxidant (Scheme 39, path a) or by deprotonation of a first-formed aromatic radical cation (paths b and c). 

The physical aspects underlying the reactivity of P-centred radicals are essential in order to benefit from the full potential offered by phosphorus-containing compounds. Hydrogen atom transfers (HATs), halogen atom abstractions, cyclisations and additions are the tool box of the widely applied free radical chemistry to date. Several authors have determined key rate constants through various physical methods, including time-resolved ESR spectroscopy and flash photolysis.3... 

Relatively straightforward but extremely useful hydrogen atom transfer (HAT) reactions involve the replacement of various X groups with hydrogen without alterations to the carbon skeleton. If the intermediate carbon radical could be intercepted by a C-C bond forming process before the HAT reaction... 

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