Electrons Electrophilic radicals

In the case of substituted aryl radicals, the results may be slightly different, depending on the polarity of the radicals. With electrophilic radicals the overall reactivity of the thiazole nucleus will decrease and the percentage of 5-substituted isomer (electron-rich position) will increase, in comparison with phenyl radicals. The results are indicated in Table III-28. 

The traditional means of assessment of the sensitivity of radical reactions to polar factors and establishing the electrophilicity or nucleophilieity of radicals is by way of a Hammett op correlation. Thus, the reactions of radicals with substituted styrene derivatives have been examined to demonstrate that simple alkyl radicals have nucleophilic character38,39 while haloalkyl radicals40 and oxygcn-ccntcrcd radicals " have electrophilic character (Tabic 1.4). It is anticipated that electron-withdrawing substituents (e.g. Cl, F, C02R, CN) will enhance overall reactivity towards nucleophilic radicals and reduce reactivity towards electrophilic radicals. Electron-donating substituents (alkyl) will have the opposite effect. 

A consequence of the selectivity for electrophilic radicals is that not all products are trapped with equal efficiency. With electron-rich monomers (e.g. S) oligomerization may complicate analysis. Other possible complications in the utilization of this method have been discussed by Russell.491... 

The fraction of head-to-head linkages in the poly(fluoro-olefms) increases in the series PVF2 < PVF PVF3 (Tabic 4.2). This can be rationalized in terms of the propensity of electrophilic radicals to add preferentially to the more electron rich end of monomers (i.e, that with the lowest number of fluorines). This trend is also seen in the reactions of trifluoromethyl radicals wilh the fluoro-olefins (see 2.3). 

Thiols react more rapidly with nucleophilic radicals than with electrophilic radicals. They have very large Ctr with S and VAc, but near ideal transfer constants (C - 1.0) with acrylic monomers (Table 6.2). Aromatic thiols have higher C,r than aliphatic thiols but also give more retardation. This is a consequence of the poor reinitiation efficiency shown by the phenylthiyl radical. The substitution pattern of the alkanethiol appears to have only a small (<2-fokl) effect on the transfer constant. Studies on the reactions of small alkyl radicals with thiols indicate that the rate of the transfer reaction is accelerated in polar solvents and, in particular, water.5 Similar trends arc observed for transfer to 1 in S polymerization with Clr = 1.4 in benzene 3.6 in CUT and 6.1 in 5% aqueous CifiCN.1 In copolymerizations, the thiyl radicals react preferentially with electron-rich monomers (Section 3.4.3.2). 

In most known examples of catalyzed aromatic nucleophilic substitution (Sr I), the preliminary step aims at producing an aromatic electrophilic radical. Such electrophilicity is obtained, in general " , by substitution on the phenyl ring with a strongly electron-withdrawing substituent (E) which also activates the leaving of the other group (X) and the creation of a transient a radical. 

The behaviour of the frontier electrons was also attributed to a certain type of electron delocalization between the reactant and the reagent 40). A concept of pseudo-n-orbital was introduced by setting up a simplified model, and the electron delocalization between the 71-electron system of aromatic nuclei and the pseudo-orbital was considered to be essential to aromatic substitutions. The pseudo-orbital was assumed to be built up out of the hydrogen atom AO attached to the carbon atom at the reaction center and the AO of the reagent species, and to be occupied by zero, one, and two electrons in electrophilic, radical, and nucleophilic reactions. A theoretical quantity called "superdelocalizability was derived from this model. This quantity will be discussed in detail later in Chap. 6. 

The attachment of an electron to an organic acceptor generates an umpolung anion radical that undergoes a variety of rapid unimolecular decompositions such as fragmentation, cyclization, rearrangement, etc., as well as bimolecular reactions with acids, electrophiles, electron acceptors, radicals, etc., as demonstrated by the following examples.135"137... 

The electron-withdrawing substituent when present in a free radical makes it more electrophilic, and electrophilic radical will seek a monomer containing an electron-releasing substituent and vice versa. 

Snider and Kwon use either cupric triflate and cuprous oxide or ceric ammonium nitrate and sodium bicarbonate as single-electron oxidants to convert d,s- and ,C-unsaturated enol silyl ethers 9 stereoselectively to the tricyclic ketones 14 in excellent yields [83, 84]. Based on comparison with other experimental data and literature results, the authors try to distinguish between several possible intermediates and propose the following mechanism with a very electrophilic radical cation 10 as the key intermediate. 

One of the most versatile methods for the preparation of 1,1-disubstituted X -phosphorins 124 was discovered by Stade who found that X -phosphorins 2 can be oxidized (mercuric acetate gives the best results) in the presence of alcohols or phenols in benzene to 1.1-dialkoxy- or l.l-diphenoxy-X -phosphorins 124. The first step is probably a reaction of the soft X -phosphorin- jr-system with the soft acid Hg which by electron transfer leads to the weakly electrophilic radical cation 58. This is then attacked by alcohol or phenol - or as Hettche has found by other nucleophiles such as an amine to form by loss of a proton the neutral X -phosphorin radical 59. This radical is oxidized once again by mercury ions leading to the formation of elemental mercury and the strongly electrophilic, short-lived X -phosphorin cation 127, which is immediately attacked by alcohol, phenol or amine. Loss of a proton then leads to the X -phosphorin 124. It is also conceivable that 59 can couple directly with a radical to form 124 (Method E, p. 82). 

A radical, often called a. free radical, is a highly reactive and short lived species with an unpaired electron. Free radicals are electron-deficient species, but usually uncharged. So their chemistry is very different from the chemistry of even-electron and electron-deficient species, e.g. carbo-cations and carbenes. A radical behaves like an electrophile, as it requires only a single electron to complete its octet. 

Fluorinated radicals play a significant role in synthetic organo-fluorine chemistry, for example, in electrophilic radical addition to alkenes, single-electron transfer reactions (SET), telomerization of fluoroalkenes with perfluoroalkyl iodides, polymerization to fluoropolymers and copolymers, and thermal, photochemical and radiation destruction of fluorocarbons. Furthermore, such free radicals are of interest for studying structures, reaction kinetics and ESR spectroscopic parameters.38... 

Additions of electrophilic radicals to electron rich aromatic rings 767... 

Radicals are often classified according to their rates of reactions with alkenes. Those radicals that react more rapidly with electron poor alkenes than with electron rich are termed nucleophilic radicals. Conversely, those that react more rapidly with electron rich alkenes than electron poor are termed electrophilic radicals. Recently, it has been found that this simple division does not suffice because certain radicals react more rapidly with both electron rich and electron poor alkenes than they do with alkenes of intermediate electron density. These radicals are termed ambiphilic. The appropriate pairing of a radical and an acceptor is important for the success of an addition reaction. 

There are several examples of the addition reactions of caibonyl-substituted radicals to alkenes by the tin hydride method. The first reaction cited in Scheme 32 is a clear-cut example of reversed electronic requirement an electrophilic radical pairing with a nucleophilic alkene.60 Because enol ethers are not easily hydrostannylated, the use of a chloride precursor (which is activated by the esters) is possible. Indeed, the use of a bromomalonate results in a completely different product (Section 4.1.6.1.4). The second example is more intriguing (especially in light of die recent proposals on the existence of ambiphilic radicals) because it appears to go against conventional wisdom in the pairing of radicals and acceptors.118,119... 

The most common and useful additives are copper(I) salts (such as CuCl), which produce high yields of 1 1 adducts in many cases.174 Several examples from the extensive work of the Ciba-Geigy group in Basel are compiled in Scheme 54, with an emphasis on subsequent conversions of the highly functionalized products into important heterocycles.175 These procedures are very simple and have been conducted on a multigram scale. Typically, the halogen component and the acceptor are heated without solvent at 110 °C in the presence of 1-10% CuCl. After several hours, the copper salts are removed by filtration and the product is isolated by distillation. It is clear that the copper additive behaves as more than just an initiator, the additions of electrophilic radicals to electron deficient alkenes like those shown in Scheme 54 would not be likely to succeed otherwise. 

In redox methods, radicals are generated and removed either by chemical or electrochemical oxidation or reduction. Initial and final radicals are often differentiated by their ability to be oxidized or reduced, as determined by substituents. In oxidative methods, radicals are removed by conversion to cations. Such oxidations are naturally suited for the additions of electrophilic radicals to alkenes (to give adduct radicals that are more susceptible to oxidation than initial radicals). Reductive methods are suited for the reverse addition of alkyl radicals to electron poor alkenes to give adducts that are more easily reduced to anions (or organometallics). 

Additions to aromatic rings can become useful when radicals and acceptors are electronically paired. The additions of electrophilic radicals to electron rich aromatic rings are growing in importance and the additions of nucleophilic radicals to electron poor alkenes have long been of preparative value. This chapter can provide only a few representative examples of each class. Giese s book is recommended as a more thorough overview of additions to aromatic rings.232... 

Similar to OH, H is an electrophilic radical (Chap. 4.4), and in its additions to C-C double bonds it has a strong preference for electron-rich sites (Das et al. 1985 Table 10.18). Thus, the C(5)-position is the preferred site of addition in the pyrimidine series as depicted here for Ura [reaction (141)]. 

One-electron oxidation systems can also generate radical species in non-chain processes. The manganese(III)-induced oxidation of C-H bonds of enolizable carbonyl compounds [74], which leads to the generation of electrophilic radicals, has found some applications in multicomponent reactions involving carbon monoxide. In the first transformation given in Scheme 6.49, a one-electron oxidation of ethyl acetoacetate by manganese triacetate, yields a radical, which then consecutively adds to 1-decene and CO to form an acyl radical [75]. The subsequent one-electron oxidation of an acyl radical to an acyl cation leads to a carboxylic acid. The formation of a y-lactone is due to the further oxidation of a carboxylic acid having an active C-H bond. As shown in the second equation, alkynes can also be used as substrates for similar three-component reactions, in which further oxidation is not observed [76]. 

---