Cyclohexadienyl radicals radical addition reactions

H" atom can both abstract hydrogen atoms and add to the double bonds. However it was found that the predominant reaction is the addition to the double bond. From the absorption of the cyclohexadienyl radical (formed by H abstraction) in acidic solution containing t-butanol (to scavenge the OH radicals) it was concluded14 that only 22% and 7% of the H atoms abstract hydrogen from 1,4- and 1,3-cyclohexadiene, respectively. 

As mentioned above, the electrochemical oxidation of a diene yields 1,2- and 1,4-addition products when the reaction is carried out in the presence of a nucleophile such as methanol or acetic acid. When the oxidation is carried out in the absence of the nucleophile it usually yields a polymeric compound as the major product. The formation of a small amount of the Diels-Alder adduct is, however, observed when the reaction is carried out in CH2CI2 with graphite anode. One of the proposed reaction pathways is shown in equation 68, though it is not clear whether the cyclohexadienyl radical serves as a diene (as shown in equation 6) or a dienophile in the Diels-Alder reaction. 

The addition of silyl radicals to double bonds in benzene or substituted benzenes (Reaction 5.2) is the key step in the mechanism of homolytic aromatic substitution with silanes [8,9]. The intermediate cyclohexadienyl radical 2 has been detected by both EPR and optical techniques [21,22]. Similar cyclohex-adienyl-type intermediates have also been detected with heteroaromatics like furan and thiophene [23]. 

Even though the aramatization mechanism from the putative cyclohexadienyl radical intermediate is not well understood (oxidation by the adventitious air is one possibility), the radical addition to an aromatic ring strategy does possess some advantages (a) no transition metal catalysis is required, (b) better yields are obtained than with similar procedures although the reaction is not regiospecific, (c) readily available starting materials may be used. 

The photocyclizations of halogenated A-benzyl-/ -phenethylamines576 are examples of reactions in which two aryl rings are connected by a chain of four atoms, one of which is a nitrogen atom. In the cases reported, one phenyl ring has a bromine atom and the other an iodine atom at the ortho position. As expected, products were formed via initial rupture of the carbon-iodine bond and these products still contained the bromine atom. In addition, however, some unexpected cyclization products were encountered, containing iodine instead of bromine. The formation of these products was ascribed to replacement of bromine by iodine in the intermediate cyclohexadienyl radicals. 

The discovery of muonic radicals in 1978 by Roduner opened up a broad field of interesting experiments. Aromatic substitution is normally studied by the measurement of the yields of stable products. This includes not only the site of addition of the reactant, but also the splitting off of the atom that is substituted. With the MuSR technique only the first step is studied exclusively. Another development concerns the measurements of the reactions of muonic radicals dimerization, ring opening, and ring closure. The observations of different reaction rates of the three isomeric muonic cyclohexadienyl radicals from anisole with quinones also opens a new field of investigation. 

The majority of the reaction proceeds via the addition channel (b) to give a methyl hydroxycyclohexadienyl radical. Cyclohexadienyl radicals are resonance stabilized and are relatively unreactive. Typical alkyl radicals add O2 rapidly with rate constants of the order of 10 12, in contrast the reaction of cyclohexadienyl and methyl cyclohexadienyl radicals with O2 proceed with rate constants of (2 - 5) x 10 16 cm3 molecule 1 s 1 [67,68]. It can be calculated that in one atmosphere of air the cyclohexadienyl radicals have a lifetime of... 

Fig. 6.21 Reactions of the 1,4-cyclohexadienyl-peroxyl radical formed by addition of O2 to the OH radical adduct of benzene (Figure 6-20), according to von Sonntag and Schuchmann (1991).

Addition of the silyl radical to carbon-carbon double bonds is an elementary reaction of radical hydrosilation (Scheme 1). Homolytic aromatic silationalso occurs involving silyl radicals. Silyl radicals are nucleophilic owing to the high SOMO energy, as evidenced by the directive effects in the hemolytic aromatic substitution. The intermediate cyclohexadienyl radicals have been observed by ESR. 

The intramolecular addition of cysteine thiyl radicals (CysS ) to phenylalanine yielding alkylthio-substituted cyclohexadienyl radicals was observed in Cys-Phe and Phe-Gly-Cys-Gly peptides.CysS radicals were generated by pulse irradiation of aqueous solution containing the respective disuHide-linked peptide [reactions (11)-(14)] ... 

The mechanism is not as straightforward as it may appear in the first step, in fact, after OH radical addition to any aromatic ring, a new colored product is formed, i.e. the cyclohexadienylic type radical may reform the conjugated system in disproportionation reactions [7,1 Oj.The process is exemplified with a substituted benzene (Scheme 1). Using high doses, and especially in the presence of O2 or O3, aldehydes and organic acids are formed from the OH-dye adducts and finally decomposed to CO2 and H2O (see upper part of Scheme 1). 

ThiyI radicals are important reactants in several enzymes and form in vivo during conditions of oxidative stress [6]. They have been considered for a long time as rather unreactive species. However, recently several reactions of thiyi radicals with biomolecules have been described (catalysis olcis-trans isomerization of unsaturated fatty acids, addition to the pyrimidine bases C5-C6 double bonds, and hydrogen abstraction from polyunsaturated fatty acid, thymine and peptide C -H and side chain C-H bonds) [7]. More recently, the intramolecular addition of peptide cysteine thiyi radicals (CysS ) to phenylalanine (Phe) yielding alkylothio-substituted cyclohexadienyl radicals was demonstrated in the peptides Phe-Cys and Phe-Gly-Cys-Gly (Fig. 2) [8]. 

Early applications of CAN in C-C bond-forming reactions were developed for the radical addition of enolizable compounds 1 to arenes 6 (Scheme 2) [5]. The intermediate cyclohexadienyl radicals are oxidized to cations by CAN and afford the substitution products 7 after deprotonation. The same concept was used for radical cyclizations [6], However, the disadvantages of such reactions are the moderate yields or regioselectivities. 

Absolute rate constants for the reaction of hydroxyl radicals with aro- matic compounds in aqueous solution have been determined in a number of pulse radiolysis investigations (6, 10, 11, 15). The rate constants were obtained directly from the formation curves of the hydroxycyclohexadienyl adduct free radical. Recent observations in this (22) and other laboratories (6, 15, 18) have shown that the cyclohexadienyl radical formed by H-atom addition has an ultraviolet absorption band which overlaps that of the hydroxycyclohexadienyl radical and is equally intense. The rate constants for the addition of hydrogen atoms to benzene and toluene (18), to phenol (15) and to benzoic acid (16) in water... 

The distribution of cyclohexadienyl radical isomers formed fiom toluene by addition of Mu, thermal or nominally hot T is very similar, suggesting that the conditions of formation are not significantly different (Table 1). In all cases addition in the ortho position occurs with higher than statistical probability, at cost of the other positions. The methyl substituent in toluene thus has a clear ortho-directing effect. Cl, F and CF3 are meta-directing, and phenoxy, COCl and CN are para-directing [12]. For hot atom reactions one normally expects a statistical distribution. 

All of these tin hydride-mediated intramolecular arylations involve an initial radical generation by reaction of BusSn with precursor 25 to afford the corresponding Cintramolecular addition onto an arene to give a stable cyclohexadienyl radical 27 which is then oxidized ( ) to the product 28 (Scheme 13.7). It should be noted that this oxidation must occur under reducing tin hydride conditions. When debate centered on the mechanism of the homolytic aromatic substitution, a number of hypotheses was proposed. Thus, in... 

The reaction between OH radicals and phenols and phenolates also takes place with addition/ elimination mechanism. The intermediate, a cyclohexadienyl-type radical, decomposes in acid/base catalyzed H2O/OH- elimination to phenoxyl radical (Land and Ebert 1967 Steenken 1987,1996 Ashton et al. 1995 Roder et al. 1999)... 

In general, radical hydrosilylation of alkenes cannot be conducted with tri-alkylsilanes, which is due to a rather strong Si—H bond in the latter. However, the hydrosilylation of carbon-carbon multiple bonds with modified silanes such as tris(trimethylsilyl)silane has been successfully used in radical hydrosilylation (16). The reversible addition of tris(trimethylsilyl)silyl [(TMSlsSi] radical to the C=C bonds is due to the ability of this radical to isomerize alkenes. The hydrosilylation of monosubstituted and gem-disubstituted olefins are efficient processes and have been shown to proceed with high regioselectivity for both electron-rich and electron-poor olefins (140). Walton and Studer presented the results of the radical hydrosilylation with silylated cyclohexadienes as radical initiators (141). The bisvinylic methylene group acts as the hydrogen donor in these reactions. H-transfer leads to a cyclohexadienyl radical (2) that subsequently rearranges to provide er -butyldimethylsilyl radical and arene (3) (see Scheme 20) (141). 

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