Radical stability, nitriles

The behavior of dibutyltin bis(dodecylmercaptide) on reaction with 4-chloro-2-pentene proved interesting (Figure 3). With only the two reactants in chlorobenzene, virtually no reaction took place up to 5 hours. However, the addition of dibutyltin dichloride resulted in a rapid reaction. Furthermore, the addition of a few milligrams of azobisisobutyro-nitrile eliminated any induction period. This latter consequence is not interpreted to result from a free radical stabilization mechanism, but it is presumed to be caused by free radical-catalyzed hydrogen chloride elimination, resulting (by neutralization with the stabilizer) in the formation... 

See reference 37. The radical-stabilizing effect of a nitrile can be estimated to be about 8 kcal mol" from the data given in this reference for the heats of formation of CH3CN and CH2CN. 

Steric Hinderance and Radical Stability Toxicity of Nitriles... 

Electron-donating functional groups, e.g. ethers, also stabilize radicals via their lone pair orbitals. However, electron-withdrawing groups can also stabilize radicals, so that radicals next to carbonyl or nitrile are more stable than even tertiary alkyl radicals. This is because these groups possess a jr electron system and the unpaired electron can take advantage... 

The low reactivity of a-olefins such as propylene or of 1,1-dialkyl olefins such as isobutylene toward radical polymerization is probably a consequence of degradative chain transfer with the allylic hydrogens. It should be pointed out, however, that other monomers such as methyl methacrylate and methacrylonitrile, which also contain allylic C—H bonds, do not undergo extensive degradative chain transfer. This is due to the lowered reactivity of the propagating radicals in these monomers. The ester and nitrile substituents stabilize the radicals and decrease their reactivity toward transfer. Simultaneously the reactivity of the monomer toward propagation is enhanced. These monomers, unlike the a-olefins and 1,1-dialkyl olefins, yield high polymers in radical polymerizations. 

Not surprisingly, nitriles that liberate cyanide more readily are more toxic. Logically, structural features that are expected to increase a-carbon radical formation and stability are likely to favor hydrogen atom abstraction from the a-carbon. The more quickly hydrogen atom abstraction occurs at the a-carbon, the more quickly cyanohydrin formation occurs and the more quickly cyanide is released and, hence, the more toxic the nitrile is expected to be. 

The reaction of aryl and hetaryl halides with the nitrile-stabilized carbanions (RC -CN) leads to derivatives of the type ArCH(R)CN. Sometimes, however, dimeric products of the type ArCH(R)CH(R)Ar are formed (Moon et al. 1983). As observed, 1-naphthyl, 2-pyridyl, and 2-quinolyl halides give the nitrile-substituted products, while phenyl halides, as a rule, form dimers. The reason consists of the manner of a surplus electron localization in the anion radical that arises upon replacing halogen with the nitrile-containing carban-ion. If the resultant anion radical contains an unpaired electron within LUMO covering mainly the aromatic ring, such an anion radical is stable, with no inclination to split up. It is oxidized by the initial substrate and gives the final product in the neutral form, Scheme 1-7 ... 

Another noticeable characteristic of captodative olefins is the influence of the reaction medium. The stabilizing effect of solvent on the persistency of a captodatively radical has been reported experimentally for the bond homolysis of bis(3,5,5-trimethyl-2-oxomorpholin-3-yl) [111], but was not found for the 2,3-diphenyl-2,3-dimethoxysuccinonitrile homolysis [112]. Theoretically the solvent-assisted stabilization las been predicted for the captodative substituted nitriles in solvent with large dielectric constants [113-114], Table 16 illustrates the solvent effect on the spontaneous thermal polymerizations [115]. The polymer yields are... 

Examples of the former take place when radical 234 is stabilized by a heteroatom. When Y is an alkoxy moiety, an oxonium is formed and trapped by several external nucleophiles [193]. When an amide was present on the starting material, as was the case with 235, amino sugars were obtained in good yields (68% for 238) [ 194]. Finally, when Y is an azide, oxidation to the a-azido cation delivers nitriles upon loss of nitrogen [195]. 

The preparation of a-selenoketones, esters, nitriles and related compounds can easily be performed via alkylation of the corresponding enolates or stabilized carbanions [21]. These compounds have found many synthetic applications in radical chemistry. In Eq. (9), a typical example involving a ketone is depicted [22]. The stability of a-selenoketones such as 41 is remarkable. Similar reactions with lactones have been performed. For instance, this approach has been applied to the stereoselective synthesis of oxygen-containing rings to either faces of a bicyclic structure [23]. The approach based on a-selenenylation/radical allyla-tion compares favorably with classical enolate allylation procedures, which usually leads to mixture of mono- and diallylated compounds. Furthermore, this strategy is excellent for the preparation of quaternary carbon centers [24] as shown by the conversion of 43 to 45, a key intermediate for the synthesis of fredericamycin A, [Eq. (10)] [25]. Similar reactions with sulfoxides [26] and phosphonates [27] have also been reported. 

Stabilized radicals are generated. A list of the main type of radical precursors used for selenium atom transfer is depicted in Fig. 1. Malonates [64, 66-73], -ketoesters [74, 75], malononitriles [76-79], haloalkanes [80], diphosphonate [81], glycolate derivatives [82, 83] and dithianes [84]. More substrates such as a-seleno-esters, -nitriles, -ketones and -sulfones can also be used, however, the efficiency of the process is reduced [68]. 

Methyl methacrylate (Fig. 1-4) and methacrylonitrile (6-5) are allylic-type monomers that do yield high molecular weight polymers in free radical reactions. This is probably because the propagating radicals are conjugated with and stabilized to some extent by the ester and nitrile substituents. The macroradicals are... 

Radicals may be generated by thermal means using, as initiators, compounds which possess either a weak 0-0 bond such as a peroxide, or which, on fragmentation, generate a stabilized radical and a strongly bonded product such as nitrogen gas. Azobisisobutyronitrile (1.59) falls into this class. After the loss of the nitrogen, the nitrile stabilizes the adjacent carbon radical by delocalization. 

In the paper cited, the following mechanism was proposed. The hydride removes the proton on the carbon a to the nitrile, leaving a carbanion. Then a benzyl radical cleaves, leaving a resonance-stabilized radical anion, 5-32. 

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