Deprotonation, of radical cations

Again, it seems to be fundamental to select the suitable oxidant or to take advantage of electrochemical methods. Moreover, the deprotonation of radical cations can be controlled by conducting the oxidation reactions in buffered media. 

However, there are some exceptions. One of them is the possibility of (photo)-protonation or -deprotonation. If a matrix is doped with sufficient amounts of a proton donor or acceptor, chances are that the substrate will give up or accept a proton already on cocondensation or on subsequent photoexcitation. In fact, the higher noble gases (Ar, Kr, Xe) are themselves good proton acceptors, forming (NG H)+ complexes that can be identified by their characteristic IR vibrations. This feature allows occasionally to observe radicals formed by deprotonation of radical cations formed in noble gas matrices, for example, benzyl radical from ionized toluene. However, we know of no examples where a carbanion was formed by deprotonation in matrices. 

When the binding energy of a hydrogen to a heteroatom is weak, heteroatom-centered radicals are readily produced by H-abstraction or one-electron oxidation followed by H+ loss. Typical examples are phenols (e.g vitamin E in non-aqueous media), tryptophan and related compounds and thiols. Deprotonation of radical cations is indeed often a source of heteroatom-centered radicals even if a deprotonation at carbon or OH addition upon reaction with water would be thermodynamically favored. The reason for this is the ready deprotonation at a heteroatom (Chap. 6.2). 

Benzyl ic ethers Tris (p-bromophenyl)amine Fast deprotonation of radical cation in the presence of a soluble base [117]... 

In conclusion, the difference in mechanisms for the main oxidation route of 68a (DIM2 mechanism) and 68b, 68c (e-p-RRC-p mechanism with fast deprotonation of radical cations) can be easily understood, taking into account that halogenated radical cations 68b+ and 68c+ are much stronger acids than 68a+ due to inductive and mesomeric effects of halogen substituent, as revealed from the equilibrium acidity estimated in DMSO (Table 3). 

While the side-chain deprotonation of radical cations prevails for alkylbenzenes, for polycyclic aromatics, attack by nucleophiles can dominate [35b, 37, 38], resulting in oxidative nucleophilic substitution (Scheme 14.6). 

Scheme 5.20 Formation of free radicals in polysaccharide via deprotonation of radical cations.

Addition of alkyllithium to cyclobutanones and transmetallation with VO(OEt)Cl2 is considered to give a similar alkoxide intermediates, which are converted to either the y-chloroketones 239 or the olefinic ketone 240 depending on the substituent of cyclobutanones. Deprotonation of the cationic species, formed by further oxidation of the radical intermediate, leads to 240. The oxovanadium compound also induces tandem nucleophilic addition of silyl enol ethers and oxidative ring-opening transformation to produce 6-chloro-l,3-diketones and 2-tetrahydrofurylidene ketones. (Scheme 95)... 

FIGURE 2.28. Comparison of high-scan-rate ultramicroelectrode cyclic voltammetry (A), redoc catalysis (A), and laser flash photolysis (x) for the determination of the rate constant of deprotonation of methylacridan cation radical by bases of increasing pKa. Adapted from Figure 6 in reference 20, with permission from the American Chemical Society. 

Formation of radicals having a lower energy than that of the starting cation-radicals is obviously favorable for their deprotonation. The cation-radicals of toluene and other alkylbenzenes are illustrative examples. As shown by Sehested and Holcman (1978), acidity of the medium does not prevent deprotonation of these cation-radicals. 

In the latter case, the aminomethylene radical is formed upon deprotonation of the cation radical. Unless proton equilibrium for one of these two radical types is much slower than for the other type, the radical that corresponds to the lowest pKa should be formed upon deprotonation of the cation radical (Et2NH)+. This cation radical has pKa = 5.3 in aqueous solutions at pH 3-9. Therefore, 02 saturation of the solutions does not affect the determined pKa (Jonsson et al. 1996). Since 02 reacts more rapidly with carbon-centered radicals than with nitrogen-centered radicals, one can conclude that deprotonation of (Et2NH)+ takes place at the nitrogen rather than at the a-carbon. 

One example is deprotonation of the cation radical of 9-benzyl-yym-nonahydro-10-selenaanthracene (Blinokhvatov et al. 1991). Upon dissolution in trifluoroacetic acid, the... 

The riboflavin triplet reacts with dGMP acid by ET (k = 6.6 x 109 dm3 mol-1 s 1), and evidence for the formation of the (deprotonated) Gua radical cation has been obtained by laser flash photolysis (Lu et al. 2000). The photosensitized reactions of dGuo by TRP is thought to follow two pathways, the formation of Z has been attributed to an ET reaction (Type I), and the reaction of singlet dioxygen [ChCAg) Type II] leads to 4-OH-8-oxo-G and 8-oxo-G (Ravanat et al. 1998). The effect of D20 and azide on the 4-OH-8-oxo-G yields shows that this... 

Treatment of arenes or heteroarenes with oxidants can lead to the formation of radical cations by SET. These radical cations can dimerize, oligomerize, or react with other radicals present in the reaction mixture deprotonation of the resulting intermediates yields the final products (Scheme 3.18). 

One electron transfer from the highest filled MO of a neutral substrate 170 (Eq. (236) ) to the anode yields a radical cation 171 as product. This may be either a transient intermediate or a stable, long-lived species depending on its substituents and the nucleophilicity of the solvent. The reaction paths of radical cations have been expertly and comprehensively reviewed by Adams 2 5 2 9 so that a short summary seems sufficient at this place. Deprotonation and 1 e-oxidation of 171 with a subsequent Sj l reaction of the resulting cation yields side-chain substitution products 172 (path a), see 9.1. Solvolysis of 171 followed by le-oxidation... 

These intra- and inter-molecular deprotonations of the cation radical readily occur, so that the cation radical is unstable even at 4 K. The direct scission of a C-H bond in the excited state PMMA cannot be excluded as an additional source of either of the main-chain radical or the side-chain radical. The H atom generated from the excited state PMMA or from the recombination of a proton with an electron will recombine with the polymer radical or abstract an hydrogen to generate also the main-chain or the side-chain radical as... 

An electrochemical study of the reaction kinetics of several substituted pyrroles has indicated that the carbon-carbon bond formation step proceeds by the coupling reaction of two cation radicals rather than the coupling of a cation radical with a neutral substrate molecule [245]. This study also indicated neutral radicals, formed by the deprotonation of the cation radicals before the carbon-carbon bond-forming step, were not involved in the coupling step. 

LSV mechanism analysis of the deprotonation of alkylbenzene cation radicals in acetonitrile"... 

Useful information about the structure of the transition state for C-H deprotonation can be obtained by comparing the relative reactivities of two series of alky-laromatic radical cations 4-MeOC6H4CH2X + [145] and 4-MeC6H4CH2X [148] (Table 3). In both instances all a-substituents (with the exception of X = tBu, see later) increase the deprotonation rate compared with X = H, although there are some discrepancies between the two series of radical cations—a-substituents of the 4-R type (OH, OMe, Me) have a much larger kinetic effect in the deprotonation of 4-MeC6H4CH2X than in that of 4-MeOC6H4CH2X , whereas the opposite behavior is observed with a -I, -R substituent such as CN. 

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). 

Interestingly, deprotonation of the cation radical can also occur at the level of the methyl group, as demonstrated in the case of 5591. 

Two alternative routes (with the same final product and electrochemical characteristics) were also considered65. They include an irreversible proton transfer from 68a+ to 68a resulting in the deprotonated radical that is coupled in a subsequent step with parent 68a or its radical cation 68a1 However, in further work107 it was shown that the oxidation peak potential Epa does not depend on the concentration of the added base. vym-collidine (which is a stronger base in water than 68a). This indicates that 68a is not able to deprotonate its radical cation 68a1 and the mechanism involves only a true nucleophilic attack of 68a onto its radical cation 68a+ , as shown in Scheme 8. 

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