Intramolecular hydrogen atom abstraction

This follows the ionisation potential of the amino groups. Both conventional and microsecond flash photolysis confirmed the involvement of intramolecular hydrogen atom abstraction and this is illustrated by the mechanistic processes in scheme 3 for an N-methyl derivative and scheme 4 for a diethylamino derivative. Here it is seen that the N-methylpiperazine derivative, does not undergo intermolecular hydrogen atom abstraction. Intramolecular hydrogen... 

The selectivity observed in most intramolecular functionalizations depends on the preference for a six-membered transition state in the hydrogen-atom abstraction step. Appropriate molecules can be constmcted in which steric or conformational effects dictate a preference for selective abstraction of a hydrogen that is more remote from the reactive radical. 

The intermediates which are generated are free radicals. The hydrogen-atom abstraction can be either intramolecular or intermolecular. Many aromatic ketones react by hydrogen-atom abstraction, and the stable products are diols formed by coupling of the resulting a-hydroxyben2yl radicals ... 

The efficiency of reduction of benzophenone derivatives is greatly diminished when an ortho alkyl substituent is present because a new photoreaction, intramolecular hydrogen-atom abstraction, then becomes the dominant process. The abstraction takes place from the benzylic position on the adjacent alkyl chain, giving an unstable enol that can revert to the original benzophenone without photoreduction. This process is known as photoenolization Photoenolization can be detected, even though no net transformation of the reactant occurs, by photolysis in deuterated hydroxylic solvents. The proton of the enolic hydroxyl is rapidly exchanged with solvent, so deuterium is introduced at the benzylic position. Deuterium is also introduced if the enol is protonated at the benzylic carbon by solvent ... 

Intramolecular hydrogen-atom abstraction is also an important process for acyclic a,/ -unsaturated ketones. The intermediate diradical then cyclizes to give the enol of a cyclobutyl ketone. Among the by-products of such photolyses are cyclobutanols resulting from alternative modes of cyclization of the diradical intermediate ... 

The success of such reactions depends on the intramolecular hydrogen transfer being faster than hydrogen atom abstraction from the stannane reagent. In the example shown, hydrogen transfer is favored by the thermodynamic driving force of radical stabilization, by the intramolecular nature of the hydrogen transfer, and by the steric effects of the central quaternary carbon. This substitution pattern often favors intramolecular reactions as a result of conformational effects. 

In this section we focus on intramolecular functionalization. Such reactions normally achieve selectivity on the basis of proximity of the reacting centers. In acyclic molecules, intramolecular functionalization normally involves hydrogen atom abstraction via a six-membered cyclic TS. The net result is introduction of functionality at the S-atom in relation to the radical site. 

There are also useful intramolecular functionalization methods that involve hydrogen atom abstraction by oxygen radicals. The conditions that were originally developed involved thermal or photochemical dissociation of alkoxy derivative of Pb(IV) generated by exchange with Pb(OAc)4.374 These decompose, giving alkoxy... 

The peroxyl radical of a hydrocarbon can attack the C—H bond of another hydrocarbon. In addition to this bimolecular abstraction, the reaction of intramolecular hydrogen atom abstraction is known when peroxyl radical attacks its own C—H bond to form as final product dihydroperoxide. This effect of intramolecular chain propagation was first observed by Rust in the 2,4-dimethylpentane oxidation experiments [130] ... 

The rate of this intramolecular isomerization depends on the chain length, with the maximum in the case of a six-atomic transition state, i.e., when the tertiary C—H bond is in the (3-position with respect to the peroxyl group [13]. For the values of rate constants of intramolecular attack on the tertiary and secondary C—H bond, see Table 2.9. The parameters of peroxyl radical reactivity in reactions of intra- and intermolecular hydrogen atom abstraction are compared and discussed in Chapter 6. 

A molecule of linear alkyl ether possesses a very convenient geometry for intramolecular hydrogen atom abstraction by the peroxyl radical. Therefore, chain propagation is performed by two ways in oxidized ethers intermolecular and intramolecular. As a result, two peroxides as primary intermediates are formed from ether due to oxidation, namely, hydroperoxide and dihydroperoxide [62],... 

Intramolecular hydrogen atom abstraction occurs rapidly in oxidized ethers. The rate constants of intramolecular hydrogen atom abstraction have the following values. 

The generation of trimethylenemethane diyls [26] has been shown to effect DNA cleavage. Attachment of this group to a DNA binding molecule (Fig. 7) made the intramolecular hydrogen atom abstraction (DNA-drug being considered as one molecule) more efficient than the competitive dimerization of diyls. 

Miwa GT, Walsh JS, Kedderis GL, et al. The use of intramolecular isotope effects to distinguish between deprotonation and hydrogen atom abstraction mechanisms in cytochrome P-450- and peroxidase-catalyzed N-demethylation reactions. J Biol Chem 1983 258(23) 14445-14449. 

The photochemical results indicate that hydrogen abstraction proceeds from the 7171" singlet excited state of thiones 20a and 20b, and was followed by pho-tocyclization. Four parameters serve to define the geometry of intramolecular hydrogen atom abstraction d. A, 0, and co, which have the values shown in Table 5. Table 7 summarizes the ideal values of d. A, 0, and co for each type of excited state along with the crystallographically derived experimental values for compounds 20a,b. 

In contrast to the photo physical processes just described, photochemical processes produce new chemical species. Such processes can be characterized by the type of chemistry induced by light absorption photodissociation, intramolecular rearrangements, photoisomerization, photodimerization, hydrogen atom abstraction, and photosensitized reactions. 

Many of the limitations of C—C bond formation by C —H insertion outlined for intermolecular reactions (Section 1.2.1.) can be overcome by making the reaction intramolecular. Thus, hydrogen atom abstraction followed by intramolecular radical-radical coupling or radical addition to an alkene are increasingly popular processes. Two-electron carbene insertions, either thermal or transition metal catalyzed, have also been used extensively. In either case, ring construction involves net C—C bond formation at a previously unactivated C-H site. 

Photochemical C —H insertion of ketone 1 proceeds by initial photoexcitation to give an excited state that can be usefully considered as a 1,2-diradical. Intramolecular hydrogen atom abstraction then proceeds to give a 1,4- or 1,5-diradical, which can collapse to form the new bond. This approach has been used to construct both four- and ftve-membered rings12 11. Photochemical-ly mediated cyclobutanol formation is known as the Norrish Type II reaction. 

Figure 4.58 Dissociation of alkylphenyl ketones following intramolecular hydrogen atom abstraction...

The case of benzoin alkyl ethers illustrated in Figure 8.15 is a remarkable example of the effect of complexation with cyclodextrins. Such molecules normally undergo homolytic dissociation in solution (the Norrish type 1 process described in section 4.4) and there is practically no intramolecular hydrogen atom abstraction (Figure 8.15). When the benzoin alkyl ethers are complexed with a cyclodextrin to form a 1 1 association, it can be shown that one of the phenyl rings fits inside the cyclodextrin cavity in aqueous solution. When the solid complex is irradiated only the photoproducts resulting from hydrogen atom transfer are detected the opposite behaviour from irradiation of the crystal of benzoin alkyl ether as well as of solutions in benzene. 

Figure 8.16 Schematic structures of the complexes leading to homolytic dissociation (type I) and intramolecular hydrogen atom abstraction (type II)...

The restricted motion of molecules and of fragments such as free radicals formed by photodissociation results in interesting differences in the photochemistry of some molecules in solution or as guests in inclusion compounds. To take one example, the aliphatic ketone 5-nonanone can yield fragmentation or cyclization products via the biradical formed through intramolecular hydrogen atom abstraction (Figure 8.18). In the photolysis of the inclusion compound the cyclization is the preferred reaction, and there is a marked selectivity in favour of the ay-isomer of the cyclobutanol. 

Absolute rate constants for intramolecular reactions of amidyl radicals have been determined by ESR spectroscopy at low temperature and extrapolated to 27°C (82JA6071). The rate constants for intramolecular 1,5-hydrogen atom abstraction, kMs, from alkyl and acyl side chains are 1 x 105 and 4 x 104 s 1, respectively. If the C-5 hydrogen on the acyl... 

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