Secondary radicals, stability

FIGURE 4 20 The bond dis sociation energies of methy lene and methyl C—H bonds in propane reveal difference in stabilities between two isomeric free radicals The secondary radical is more stable than the primary... 

In the mass spectrum (Figure 8) of the corresponding ketal of 5-deoxy-D-xt/Zo-hexose, 5-deoxy-l,2-0-isopropylidene-D- rt/Zo-hexofuranose (11), the peak from C-4-C-5 cleavage, m/e 159, is of minor relative intensity. Since the ions at m/e 159 are the same from both isomers, 10 and 11, the intensity difference must be attributable to the lower stability of the primary radical formed from C-5 of 11 compared with the secondary radical from 10 ... 

Stabilize a neighboring, empty p-orbital, so too, alkyl groups can stabilize a neighboring, partially filled orbital. This preference for forming a tertiary radical (rather than a secondary radical) dictates that Br" will attack the less substituted carbon. This explains the observed anti-Markovnikov regiochemistry. 

The effects of substitutents on the y-carbon on the efficiency of the type II cleavage are presented in Table 3.15.<89) These data indicate that the rate constant of cleavage increases as the strength of the y C—H bond decreases, that is, from a primary to a secondary to a tertiary hydrogen atom. The substitution of groups capable of radical stabilization, such as — or... 

Both -NH2 and -COOH groups are hydrophilic esterifying the -COOH group under acidic conditions would render surfactant properties to the final derivative (Figure 3). If both the -COOH and -NH2 functionalities of the amino acid are derivatized, making it a secondary amino compound, then it can be used as fuel stabilizer, although the exact mechanism of -NH- as free radical stabilizer is still uncertain. 

Quite surprisingly, 28a and 29a are formed from 28 and 29 with about the same reaction energy (A E -4.0 kcal mol" ), even though secondary radicals are more stable than primary radicals by approximately 3 kcal mol-1 based on their bond dissociation energies. This must be due to steric interactions with the cyclopentadienyl ligand in 29a, which fully counterbalances the radical s increased stability. A similar trend of product stability is observed in the formation of the less favored primary radicals 29b and 30b. The formation of 30a is more favorable by 4.5 kcal mol 1 compared to 29a. This is even higher than the stability difference between a tertiary and a secondary... 

In the case of asymmetrical ketones, two different modes of a-cleavage can occur, with the major products being formed via the more stable pair of initially-formed radicals. For alkyl radicals, the stability of the radical increases as its complexity increases and radical stabilities are tertiary > secondary > primary. 

Although a radical is neutral, it is an electron-dehcient species that will be very reacdve as it attempts to pair off the odd electron. Because radicals are electron dehcient, electron-releasing groups such as alkyl groups tend to provide a stabilizing effect. The more electron-releasing groups there are, the more stable the radical. Thus, tertiary radicals are more stable than secondary radicals, which in turn are more stable than primary radicals. 

Now, just the same sort of rationalization can be applied to the radical addition, in that the more favourable secondary radical is predominantly produced. This, in turn, leads to addition of HBr in what is the anti-Markovnikov orientation. The apparent difference is because the electrophile in the ionic mechanism is a proton, and bromide then quenches the resultant cation. In the radical reaction, the attacking species is a bromine atom, and a hydrogen atom is then used to quench the radical. This is effectively a reverse sequence for the addition process but, nevertheless, the stability of the intermediate carbocation or radical is the defining feature. The terminologies Markovnikov or anti-Markovnikov orientation may be confusing and difficult to remember consider the mechanism and it all makes sense. 

Introduction of a methyl group at the 4-/1 position actually resulted in increased activity, because of the additional stabilization of the secondary C4 radical. A series of trioxanes 25-32 were prepared to determine the effect of C4 substitution on antimalarial activity. The functionalities introduced included radical stabilizing groups (methyl, phenyl, benzyl, CH2TMS) and CH2SnR3 (R = Me, Bn) designed to intercept the C4 radical. As previously observed, for all compounds with measurable antimalarial activity the S-isomers were more antimalarially active than the a-isomers. 

There are many excellent books and reviews on the structure and reactions of secondary radical ions generated in radiolytic and photolytic reactions. Common topics include the means and kinetics of radical ion production, techniques for matrix stabilization, electronic and atomic structure, ion-molecule reactions, structural rearrangements, etc. On the other hand, the studies of primary radical ions, viz. solvent radical ions, have not been reviewed in a systematic fashion. In this chapter, we attempt to close this gap. To this end, we will concentrate on a few better-characterized systems. (There have been many scattered pulse radiolysis studies of organic solvents most of these studies are inconclusive as to the nature of the primary species.)... 

Another relevant example is the pyrolysis of cnt/ -2,7,7-trimethylbicyclo[3.1.1]hept-2-en-6-ol (21) at 430 =C, which produces a mixture of several products. Gas chromatographic separation gives, among many other compounds, 3,7-dimethylocta-3,6-dienal (23) and 3,7-dimethylocta-2,6-dienal (24) in 13 and 6% yield, respectively.107 As can be seen in the diradical 22, the C — C double bond is able to offer 71-stabilization to the secondary radical. For this reason, the 1,4-diradical is generated exclusively.107... 

In support of the above mechanism, (lS,2S,57 )-2,6,6-trimethylbicyclo[3.1. l]heptan-3-one [(-)-isopinocamphone, 22] does not yield a hydrogen transfer product because its carbonyl group is unable to provide -stabilization to the corresponding secondary radical.106... 

The latter proposal would lead one to conclude that radical 56, having a cyclopropane ring and a resonance-stabilized secondary radical, is more stable than is the isomeric form 55, which has a conjugated ketone and a primary radical. The product, therefore, is one derived from the intermediate 56. In the case where the 19-oxime is formed without any rearrangement, the initially formed intermediate 57, having a double bond and a primary radical, would be more stable than is the isomeric form 58, which contains a cyclopropane ring and a secondary radical. 

This secondary carbon position offers the best combination of free radical stability and ability to approach the enzyme s reactive site. This addition product could be further transformed to yield 2-carboxy-substituted compounds (So and Young, 1999), derivatives that are subsequently used in pathways involving fatty acids. 

Tables 9.3 and 9.4 list selected bond dissociation energies and radical heats of formation. Note particularly that the decrease in energy required to remove hydrogen in the series methane, primary, secondary, tertiary, parallels increasing radical stability, and that aldehydic, allylic, and benzylic hydrogens have bond dissociation energies substantially lower than do alkyl hydrogens.

Since the order of free-radical stabilities falls in the order 3° > 2° > 1°, product stability would dictate that cyclization should preferentially occur to give die more stable secondary radical—a six-membered ring in reaction (9.1) (path a) and a seven-membered ring in reaction (9.2)(path a). 

The reactions between free radicals and flavonoids (or polyphenols) are assumed to form aroxyl radicals (PO) (reaction 8). The stability of these secondary radical species is an important element to be considered in their antioxidant actions. Flavonoids with similar reduction potentials can originate radicals with very different reactivity toward other molecules present in biological systems. While a stable and relatively nonreactive PO is also nonreactive to propagate the chain reaction, a high reactive PO would propagate rather than interrupt a chain reaction. 

Table 1.2 illustrates an additional substituent effect on radical stability. Here the dissociation enthalpies of reactions that lead to (poly)alkylated radicals (alk)3-nHnC are listed ( alk stands for alkyl group). From these dissociation enthalpies it can be seen that alkyl substituents stabilize radicals. A primary radical is by 4 kcal/mol more stable, a secondary radical is by 7 kcal/mol more stable, and a tertiary radical is by 9 kcal/mol more stable than the methyl radical. 

The discrepancy from the experimental values is due to the fact that H atoms bound to different types of C atoms are replaced by chlorine at different rates. The substitution of Cfcrt— H takes place via a tertiary radical. The substitution of Csec—H takes place via the somewhat less stable secondary radical, and the substitution of Cprjm—H takes place via even less stable primary radicals (for the stability of radicals, see Table 1.2). According to Hammond s postulate, the rate of formation of these radicals should decrease as the radical s stability decreases. Hydrogen atoms bound to Ctert should thus be substituted more rapidly than H atoms bound to Csec, and these should in turn be substituted by Cl more rapidly than H atoms bound to Cprjm. As the analysis of the regioselectivity of the monochlorination of isopentane carried out by means of Table 1.4 shows, the relative chlorination rates of C —H, C —H, and C. —H are 4.4 33 1, in agreement with this expectation. 

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