Radical heterolysis

Simple mechanistic considerations easily explain why heterolytic dissociation of the C — N bond in a diazonium ion is likely to occur, as a nitrogen molecule is already preformed in a diazonium ion. On the other hand, homolytic dissociation of the C —N bond is very unlikely from an energetic point of view. In heterolysis N2, a very stable product, is formed in addition to the aryl cation (8.1), which is a metastable intermediate, whereas in homolysis two metastable primary products, the aryl radical (8.2) and the dinitrogen radical cation (8.3) would be formed. This event is unlikely indeed, and as discussed in Section 8.6, homolytic dediazoniation does not proceed by simple homolysis of a diazonium ion. 

Crich D, Brebion F, Suk D-H (2006) Generation of Alkene Radical Cations by Heterolysis of -Substituted Radicals Mechanism, Stereochemistry, and Applications in Synthesis. 263-. 1-38... 

The formation of free radicals and alcohol (in addition to the products of hydroperoxide heterolysis) implies that the catalytic decomposition of hydroperoxide occurs both hetero-lytically and homolytically. The mechanism of homolytic hydroperoxide decomposition was proposed by Van Tilborg and Smael [48]. 

The functionalization reaction as shown in Scheme 1(A) clearly requires the breaking of a C-H bond at some point in the reaction sequence. This step is most difficult to achieve for R = alkyl as both the heterolytic and homolytic C-H bond dissociation energies are high. For example, the pKa of methane is estimated to be ca. 48 (6,7). Bond heterolysis, thus, hardly appears feasible. C-H bond homolysis also appears difficult, since the C-H bonds of alkanes are among the strongest single bonds in nature. This is particularly true for primary carbons and for methane, where the radicals which would result from homolysis are not stabilized. The bond energy (homolytic dissociation enthalpy at 25 °C) of methane is 105 kcal/mol (8). 

In parallel with the development of the heterolysis of b-substituted alkyl radicals, a rearrangement reaction was observed and extensively studied in organic solvents. This rearrangement was first noted for b-(acyloxy)alkyl radicals (Scheme 5) by Surzur et al. [48] and, later, for b-(phosphatoxy)alkyl radicals by the Crich and Giese groups [49,50]. 

At one time considered as two distinct reactions occurring by different mechanisms [51], the fragmentations of Scheme 2 and the rearrangments of Scheme 5 are now seen as different facets of the same fundamental heterolysis of -substituted alkyl radicals into alkene radical cations, with the eventual outcome determined by the reaction conditions [52],... 

Equation lb, b is the defining equation for the addition-elimination route for one-electron transfer between X" and Y. It is important to note that although X-Y is a radical and the overall reaction results in the transfer of a single electron, in the actual electron transfer step an electron pair is shifted rather than a single electron [5]. This means that electron transfer is the consequence of a heterolysis reaction in which the electron pair joining X and Y ends up at... 

Concerning the general reaction Scheme 1, attention is restricted to two special areas A), cases where X is a carbon-centered radical and Y is an oxygen atom joined by a double bond to some center Z (Eq. 4), and B), cases where X is a hetero atom, in most cases oxygen centered radical and Y is a carbon (Eq. 5) [11]. One is then dealing with formation and heterolysis of a bond between a carbon- and a hetero-atom. Of the two, the hetero-atom is of course always more electron-affinic and therefore in the heterolysis the electron pair joining the two will go to the hetero-atom. 

The hetero atom E at is required for two reasons (a) to make the addition (of C, ) to the nitro group possible (by providing the necessary nuc-leophilicity [13] to the radical [14], and (b) to stabilize the (incipient) carboca-tion that results from the heterolysis. The features (a) and (b) are interrelated by... 

For those systems where Ri = R2 = H or Ri = H, R2 = CH3, i.e. where the number of alkyl groups at C, is <1, and R3 = H to NO3, the alkoxynitroxyl radicals formed according to Eq. 7 under steady-state-ESR or pulse radiolysis conditions do not give rise to nitrobenzene radical anions. This means that the rate constants for heterolysis of the nitroxyls are < 10 s . This is not only true in weakly acidic (pH 4) or neutral but also in strongly alkaline solution (pH 13-14). The latter observation means that the nitroxyls are not susceptible to base catalyzed heterolysis. From this the rate constant for OH catalyzed decomposition can be estimated to be < 10 M s [19]. This low number for... 

At pH < 7 the nitroxyl radicals do not undergo an observable heterolysis (khs 10 s ), but decay by bimolecular reactions. However, in basic solution an OH -catalyzed heterolysis takes place to yield the radical anion of the nitrobenzene and an oxidized pyrimidine. In the case of the nitroxyls substituted at N(l) by H (i.e. those derived from the free bases), the OH catalysis involves deprotonation at N(l) which is adjacent to the reaction site [= C(6)] (cf. Eq. 15) [26] ... 

Deprotonation provides the necessary electron push to kick out the electron pair joining C(6) with the nitrobenzene oxygen. If, however, N(l) is alkylated (as with the nucleosides and nucleotides), OH catalysis is much less efficient since it now proceeds by deprotonation from N(3) (with the uracils) or from the amino group at C(4) (with the cytosines). In these cases the area of deprotonation is separated from the reaction site by a (hydroxy)methylene group which means that the increase in electron density that results from deprotonation at N(3) is transferable to the reaction site only through the carbon skeleton (inductive effect), which is of course inefficient as compared to the electron-pair donation from N(l) (mesomeric effect) [26]. Reaction 15 is a 1 1 model for the catalytic effect of OH on the heterolysis of peroxyl radicals from pyrimidine-6-yl radicals (see Sect. 2.4). 

The 5,6-dihydropyrimidine-6-yl radicals discussed above behave, in their reactions with nitrobenzenes, like the simpler radicals CH2OH and CH(al-kyl)Oalkyl do, i.e. they react exclusively by addition to give nitroxyl radicals and uncatalyzed heterolysis is not observed (khs < 10 s ). If, however, a methyl group is introduced at C(6) (= CJ of the pyrimidine-6-yl radical, the corresponding nitroxyl radicals heterolyze with rate constants at 20 °C of 10 to 5 X 10 s depending on the structure of the pyrimidine and of the nitrobenzene (Eq. 16). This SnI type reaction is characterized by activation enthalpies of 30-40 kJ mol and activation entropies of — 89 to — 7 Jmol K (entropy control) [27]. The rate-enhancing effect of the methyl group is, of course, due to... 

Stabilization of the (incipient) C 6) carbocation developing in the C-O heterolysis. The rate constants for the heterolysis reaction are a measure of the reducing power of 5,6-dihydro-6-methylpyrimidine-6-yl radicals. On this basis, the cytosine radicals are better reductants than the corresponding uracil radicals, and the radicals derived by hydrogen atom addition to pyrimidines are stronger reductants than those formed by OH radical addition [27]. 

It was mentioned above that acetalic nitroxyl radicals produced by addition of a-alkoxyalkyl radicals to tetranitromethane (TNM) undergo a spontaneous heterolysis with the carbon center being oxidized and TNM reduced (to nitro-form anion (NF ) and NOj). In order to see the addition-elimination sequence with acyclic a-alkoxyalkyl radicals there have to be two (electron-withdrawing relative to methyl) hydrogens at Q. Even one alkyl group at Q is sufficient to make khs > 10 s and therefore too fast to measure. If, however, an alkyl group which is inductively deactivated is introduced at Q, the k values fall in the... 

This quinone reacts in aqueous solution with OH and H adducts of cytosines and uracils by an electron transfer/addition mechanism, similar to Eq. 18 [28], Addition takes place at the quinone carbonyl oxygen to produce an anthroxyl radical. This then undergoes spontaneous C-O heterolysis ... 

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