Quinone Oxidations Hydrogen Transfer Reactions

The oxidation of hydroarenes to arenes by quinones such as 2,3-dichloro-5,6-dicyano-l,4-quinone (DDQ) is frequently used for the synthesis of aromatic compounds. Brower et al. have already shown that the dehydrogentaion 1,4-cyclo-hexadiene to benzene [128] or tetraline to naphthalene [129] by thymoquinone is accelerated by pressure giving a negative volume of activation ((AV = —33 (75 °C) and —28 (175 °C) cm mol respectively). A similar effect of pressure has been observed for the oxidation of leuco crystal violet with p-chloranil ((AV = -25 cm mol (21 °C) [130]. The pressure-dependent kinetic isotope effect of this reaction (29 °C kn/ D = H-5 (1 bar) and 8.2 (1.5 kbar)) indicates that hydrogen transfer occurs in the rate-determining step. The large kn/ko value at 1 bar and it pressure dependence was attributed to a quantum mechanical tunneling. 

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Ruthenium compounds are widely used as catalysts for hydrogen transfer reactions. These systems can be readily adapted to the aerobic oxidation of alcohols by employing dioxygen, in combination with a hydrogen acceptor as a cocatalyst, in a multistep process. These systems demonstrate high activity. For example, Backvall and coworkers [146] used low-valent ruthenium complexes in combination with a benzoquinone and a cobalt-Schiffs base complex. Optimization of the electron-rich quinone, combined with the so-called Shvo Ru-cata-lyst, led to one of the fastest catalytic systems reported for the oxidation of secondary alcohols (Fig. 4.59). 

The oxidation of secondary amines to imines can be carried out by hydrogen transfer reaction under mild conditions using a catalytic amount of 9/2,6-dimethoxy benzo-quinone/Mn02 (Eq. 3.30) [65]. 

The Shvo catalyst 1 can participate in the transfer of hydrogen from one molecule to another. Such hydrogen transfer reactions are useful in synthetic organic chemistry for the reduction of ketones (aldehydes) and imines, and for the oxidation of alcohols and amines. In the former case (transfer hydrogenation), a hydrogen donor such as isopropanol or formic acid is used, which reduces the carbonyl compound or imine to alcohol or amine, respectively. In the oxidation of alcohols and amines (transfer dehydrogenation), a hydrogen acceptor such as acetone or a quinone is used. 

The temperature used in the oxidation of the diols 3,35°C, is probably the lowest temperature reported for a hydrogen transfer reaction with the Shvo catalyst The aerobic oxidation of secondary alcohols using Shvo s catalyst 1 was recently combined with an efficient hybrid electron transfer mediator 5 (6) [47, 48], This leads to a facile aerobic oxidation via transfer dehydrogenation, whereas the previous system (cf. electron transfer system of Scheme 3) [41, 42] with separate quinone and metal macrocycle now has been modified by tethering the quinone to the metal macrocycle (Scheme 3). 

The most important reaction of dihydropyrimidines is their oxidation to the corresponding pyrimidines (via dehydrogenation, hydrogen transfer, or disproportionation). However, although many such oxidations have been carried out, they were aimed at enabling identification of dihydropyrimidines from the pyrimidine formed, rather than a study of the kinetics and mechanism of the oxidation reactions themselves. Thus besides spontaneous oxidation in air, l,4(l,6)-dihydropyrimidines were oxidized by KMn04,152 15S 156,171-173 DMSO,147-151153 or potassium hexacyanoferrate(III)187 1,2-dihydropyrimidines were oxidized by KMn04,175 176 178 183 184 DMSO,163 or 2,3-dichloro-5,6-dicyanobenzo-quinone (DDQ).199... 

Other studies have dealt with hydrogen abstraction from the solvent by the photosensitizing drug nalidixic acid [98a], hydrogen transfer in an-thraquinone/xanthene systems [98b], photoreductions of quinones by alcohols [98c] and of acetylenic ketones by various hydrogen donors [98d], the oxidation of NADH analogues [98e-98g], and the reaction of 4-methyl-2-quinolinecarbonitrile with optically active phenylpropionic acid [98h],... 

Since both alcoholic oxidation and O2 reduction are two-electron processes, the catalytic reaction is conceptually equivalent to a transfer of the elements of dihydrogen between the two substrates. Biological hydrogen transfer generally involves specialized organic redox factors (e.g., flavins, nicotinamide, quinones), with well-characterized reaction mechanisms. Galactose oxidase does not contain any of these conventional redox factors and instead utilizes a very different type of active site, a free radical-coupled copper complex, to perform this chemistry. The new type of active site structure implies that the reaction follows a novel biochemical redox mechanisms based on free radicals and the two-electron reactivity of the metalloradical complex. 

Subsequent one-electron transfer and intramolecular hydrogen migration lead to radical 102 followed by reaction with 02 to yield hydroperoxide radical 103. Radical 103 is further oxidized to a dihydroperoxide (104), which decomposes to anthra-quinone. Alternatively, 103 may be transformed to a diradical that eventually gives anthracene as a byproduct. The ratio of the two products strongly depends on the solvent used. The highest yield of anthraquinone (85% at 100% conversion) was achieved in 95% aqueous pyridine. 

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