Ketyl radicals, hydrogen transfer

The inhibitory function of the sulfur compounds then would appear to be to prevent the subsequent reaction of the initially formed ketyl radicals by catalyzing hydrogen transfer reactions. With this in mind, one can write the following mechanism for the inhibition of the photoreduction of benzo-phenone by sulfur compounds ... 

When camphorquinone, which is known to scavenge all free ketyl radicals by hydrogen transfer,<74,76> was added to the photolysis mixture only the mixed pinacol and benzhydrol were produced, in the ratio of 1 to 0.8, respectively ... 

We saw earlier that when benzophenone is photoreduced in the presence of optically active 2-butanol, the alcohol recovered from the reaction loses no optical activity/541 This was presented as evidence that there could be no appreciable reversibility of the initial hydrogen abstraction since this should lead to racemization of the unreacted alcohol. However, if one uses relabeled benzhydrol and examines the initially produced benzpinacol for the presence of the label, one finds that the product pinacol contains no 14C. This would indicate that there must be some type of rapid transfer of the hydrogen radical from the ketyl radical produced upon abstraction from benzhydrol,... 

This reaction is the reverse of the initial ketyl radical formation by the benzophenone triplet and is therm Q4ynamically favorable. The experiments using optically active alcohols as source of hydrogen atoms show, however, that under normal conditions this reaction is unimportant. This is probably due to other, more efficient pathways for reaction of the ketyl radicals or perhaps to diffusion rates which separate the radicals before reverse transfer can occur. That this reaction can be important in some cases even without the presence of sulfur compounds was shown by studying the photoreduction of benzophenone in optically active ethers.<68) Although the reaction of benzophenone in methyl 2-octyl ether is only 0.17 times as fast as that in isopropanol, ethers can be used as sources of hydrogen atoms for photoreduction ... 

Since transfer of a second hydrogen atom from the ether radical is unreasonable, a pathway available to the acetone ketyl radical in the photoreduction in isopropanol is removed in this system and reverse transfer can occur ... 

At 0.1M acceptor, for example, the rate of energy transfer is 19.2 times the rate of abstraction. However, this means that about 5% of the benzophenone triplet will still abstract from the solvent to form ketyl radicals. A compound which is itself a poor hydrogen abstractor may show a greatly enhanced quantum yield of photoreduction under these conditions. 

In a study of the quenching of benzophenone photoreduction with biacetyl, it was observed that the biacetyl was consumed.116 This phenomenon also is readily explained by chemical quenching, transfer of a hydrogen atom from the benzophenone ketyl radical to biacetyl to form the biacetyl ketyl radical and ultimately the pinacol derived from biacetyl. 

Figure 4.26 Chemical sensitization through hydrogen atom transfer between a ketyl radical and acridine...

The electrocarboxylation of aldehydes and ketones leads to the corresponding a-hydroxycarboxylic acids that can easily be converted into carboxylic acids via a hydrogenation reaction [7]. It has been reported that the electrocarboxylation of aromatic ketones occurs through the reaction of C02 onto the activated carbon atom of the carbonyl group of the ketyl radical anion generated upon electron transfer to the ketone [7]. Otherwise, the aforementioned intermediate is likely to be a resonance hybrid (see Equation 12.23), and its electrophilic reaction with C02 may take place both at the carbon or the oxygen atom [42, 43]. 

Becker, H.-D. Sanchez, D. Hydrogen transfer by ketyl radicals the reductive dimerization of quinone methides. Tetrahedron Lett. 1975, 3745-3748. 

Rapid hydrogen transfer occurs between semidione radicals and ground state diketones. This w as illustrated by irradiation of a mixture of camphorquinone (174, A-max 470 nm, Ex = 51 kcal/mole) and tetralindione 68 (Amax 388 nm, ET = 54 kcal/ mole) in 2-propanol at various wavelengths 141). The exclusive product, no matter what the wavelength, was reduced 68 indicating that the equilibrium below lies to the right. Ketyl radicals derived from monoketones, such as benzophenone, transfer... 

Cyclopropyl-substituted ketones are suitable substrates for generating distonic radical anions from ketyl radical anions. A series of cycloalkanone substrates with unsaturated side-chains, to trap the primary radical formed after cyclopropylcar-binyl ring opening, has been investigated (Scheme 31) [118, 119]. For the first electron-transfer step triethylamine is used as electron donor. The reaction sequence is terminated by proton or hydrogen transfer from the solvent or the a-amino radical formed after deprotonation of the amine radical cation. 

The hydrogen atom transfer is proposed to result in a substrate derived ketyl radical (3), which then would be oxidized through electron transfer to the copper center, yielding Cu(I) and the aldehyde product (4). As mentioned above, these two steps have been proposed by Branchaud and co-workers to occur in a concerted manner [21]. 

To summarize this section, the theoretical calculations [2] strongly support the mechanism proposed for galactose oxidase. It was shown that the proton transfer step proposed to initiate the oxidation of the substrate is very fast and just slightly exothermic. The rate-limiting hydrogen atom transfer step has a calculated barrier of feasible 13.6 kcal/mol. The proposed short-lived ketyl radical intermediate has been localized, and it was argued that the subsequent... 

In the first step the spectroscopically detectable ketyl radical 36 is formed, which then recombines to form benzopinacol (37) (Weiner, 1971). The same pinacol is obtained by reacting benzophenone with 2-propanol, since the dimethylketyl radical (38) produced in the hydrogen abstraction step is a strong reductant and transfers a hydrogen atom to the excess benzophenone to form another molecule of the diphenylketyl radical (36). 

---