Hydrogen-atom transfer reaction

We have seen that substitution, addition, and group transfer reactions can occur intramolecularly. Intramolecular substitution reactions that involve hydrogen abstraction have some unique synthetic applications because they permit functionalization of carbon atoms relatively remote from the initial reaction site4 The preference for a six-membered cyclic TS in the hydrogen abstraction step imparts position selectivity to the process. 

There are several reaction sequences that involve such intramolecular hydrogen abstraction steps. One example is the photolytically initiated decomposition of A-haloamines in acidic solution, which is known as the Hofmann-Loejfler reaction The reaction leads to y-haloamines, but these are usually converted to pyrrolidines by intramolecular nucleophilic substitution. 

There are related procedures involving A-haloamides that lead to lactones via iminolactone intermediates.  

Intramolecular hydrogen abstraction reactions have also been observed in medium-sized rings. The reaction of cyclooctene with carbon tetrachloride and bromotrichloromethane is an interesting case. As shown in the equations below. 

In the case of carbon tetrachloride, the radical intermediate undergoes two competing reactions transannular hydrogen abstraction is competitive with abstraction of a chlorine atom from carbon tetrachloride. The former reaction leads to the 

A number of studies of H-atom transfer from hydrogen halides to free radicals, R + HX - RH + X, have been done by FPTRMS in which R was detected by photoionization, and its decay was monitored as a function of [HX] under pseudo-first-order conditions. When the rate coefficient is combined with determinations of the rate coefficient of the reverse reaction to obtain the equilibrium constant, the enthalpy of formation of the radical can be deduced. If the kinetics are accurately measured in isolation, this is a direct kinetic method which can be used to confirm (or otherwise) thermodynamic data obtained by classical, indirect kinetic methods which depend on correct mechanistic interpretation. In a number of instances free radical enthalpies of formation by these two different approaches have not been in good agreement. It is not the purpose of this short survey to discuss the differences, but rather to briefly indicate the extent to which the FPTRMS method has contributed to the kinetics of these reactions and to free radical thermochemistry. 

FLASH PHOTOLYSIS WITH TIME-RESOLVED MASS SPECTROMETRY 

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Vitamin E actually consists of a family of compounds, the most active of which is a-tocopherol. The mechanism of the vitamin s action is not completely certain, but it seems likely that it might undergo hydrogen atom transfer reactions with free radicals to give a stable radical (see also Chapter 17, Problem 7). 

Quantification of antioxidant action usually relies on the reducing ability of antioxidants, measured either by electron transfer, reaction [16.15], or by hydrogen atom transfer reactions, reaction [16.16] ... 

Lewis, E. S. Isotope Effects in Hydrogen Atom Transfer Reactions. 74, 31-44 (1978). 

Free Radical Substitution and Hydrogen Atom Transfer Reactions... 

FREE RADICAL SUBSTITUTION AND HYDROGEN ATOM TRANSFER REACTIONS... 

Hydrogen atom transfer implies the transfer of hydrogen atoms from the chain carrier, which is the stereo-determining step in enantioselective hydrogen atom transfer reactions. These reactions are often employed as a functional group interconversion step in the synthesis of many natural products wherein an alkyl iodide or alkyl bromide is converted into an alkane, which, in simple terms, is defined as reduction [ 19,20 ]. Most of these reactions can be classified as diastereoselective in that the selectivity arises from the substrate. Enantioselective H-atom transfer reactions can be performed in two distinct ways (1) by H-atom transfer from an achiral reductant to a radical complexed to a chiral source or alternatively (2) by H-atom transfer from a chiral reductant to a radical. 

Enantioselective synthesis of /1-amino acids is important as they are present in various natural products and in many biologically active compounds [26,27]. Several methods exist for the enantioselective synthesis of -substituted /1-amino acids (/l3-amino acids) however, synthesis of a-substituted /1-amino acids (/l2-amino acids) is very limited [28,29]. A report on highly enantioselective hydrogen atom transfer reactions to synthesize /l2-amino acids (Scheme 9) has recently been described [30]. 

An understanding of kinetic acidity is necessary in order to distinguish such mechanisms from other ways in which hydrogen may become attached to a substrate, e.g., hydrogen atom transfer, reaction 8, and hydride transfer, reaction 9. 

Hydride-transfer reactions involving other cofactors 64 Hydrogen-atom transfer reactions 67 Proton-transfer reactions 69 Experimental signatures of tunneling 70... 

Tajima, S. Azami, T. Shizuka, H. Tsu-chiya, T. An Investigation of the Mechanism of Single and Double Hydrogen Atom Transfer Reactions in Alkyl Benzoates by the Ortho Effect. Org. Mass Spectrom. 1979,14,499-502. 

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... 

Triplet carbenes have a singly occupied p orbital, as is the case for radicals, and hence react like those radicals. Hydrogen atom transfer reactions are fundamental reaction pathways of triplet carbenes. The reaction of a triplet carbene with a hydrocarbon is quite analogous to the free radical hydrogen atom transfer process (Scheme 9.6). 

Figure 10.9 shows the orbital interactions for typical hydrogen atom transfer reaction. It is in fact the same diagram that described proton and hydride transfers (Figures 10.1 and... 

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