Radical Aromatic Substitutions

Aromatic Substitution Reactions Involving Radical Intermediates 11.4.1. Aromatic Radical Substitution 

Aromatic rings are moderately reactive toward addition of free radicals (see Part A, Section 12.2) and certain synthetically useful substitution reactions involve free radical substitution. One example is the synthesis of biaryls.175 

There are some inherent limits to the usefulness of such reactions. Radical substitutions are only moderately sensitive to substituent directing effects, so that substituted reactants usually give a mixture of products. This means that the practical utility is limited to symmetrical reactants, such as benzene, where the position of attack 

In the classical procedure, base is added to a two-phase mixture of the aqueous diazonium salt and an excess of the aromatic that is to be substituted. Improved yields can be obtained by using polyethers or phase transfer catalysts with solid aryl diazonium tetrafluoroborate salts in an excess of the aromatic reactant.177 Another source of aryl radicals is A-nitrosoacetanilides, which rearrange to diazonium acetates and give rise to aryl radicals via diazo oxides.178 

A procedure for arylation involving in situ diazotization has also been developed.179 

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A titanium-radical-initiated radical substitution was reported by Gansauer, Flowers II, et al. [64], in which the radical metal complex CpjTiCl opened the epoxide ring in 181 followed by subsequent aromatic radical substitution to form an indo-line 183 via 182 (Scheme 5.39). This was readily converted into product 184 by hydrogen abstraction in excellent yields (92-98%). 

Toluene, an aLkylben2ene, has the chemistry typical of each example of this type of compound. However, the typical aromatic ring or alkene reactions are affected by the presence of the other group as a substituent. Except for hydrogenation and oxidation, the most important reactions involve either electrophilic substitution in the aromatic ring or free-radical substitution on the methyl group. Addition reactions to the double bonds of the ring and disproportionation of two toluene molecules to yield one molecule of benzene and one molecule of xylene also occur. 

First reported by Fredenhagen in 1926 F3, F4), the graphite-alkali-metal compounds possess a relative simplicity with respect to other intercalation compounds. To the physicist, their uncomplicated structure and well defined stoichiometry permit reasonable band-structure calculations to be made S2,12) to the chemist, their identity as solid, "infinite radical-anions frequently allows their useful chemical substitution for such homogeneous, molecular-basis reductants as alkali metal-amines and aromatic radical anions N2, B5). 

In Part 2 of this book, we shall be directly concerned with organic reactions and their mechanisms. The reactions have been classified into 10 chapters, based primarily on reaction type substitutions, additions to multiple bonds, eliminations, rearrangements, and oxidation-reduction reactions. Five chapters are devoted to substitutions these are classified on the basis of mechanism as well as substrate. Chapters 10 and 13 include nucleophilic substitutions at aliphatic and aromatic substrates, respectively, Chapters 12 and 11 deal with electrophilic substitutions at aliphatic and aromatic substrates, respectively. All free-radical substitutions are discussed in Chapter 14. Additions to multiple bonds are classified not according to mechanism, but according to the type of multiple bond. Additions to carbon-carbon multiple bonds are dealt with in Chapter 15 additions to other multiple bonds in Chapter 16. One chapter is devoted to each of the three remaining reaction types Chapter 17, eliminations Chapter 18, rearrangements Chapter 19, oxidation-reduction reactions. This last chapter covers only those oxidation-reduction reactions that could not be conveniently treated in any of the other categories (except for oxidative eliminations). 

Free-radical substitution at an aromatic carbon seldom takes place by a mechanism in which a hydrogen is abstracted to give an aryl radical. Reactivity considerations here are similar to those in Chapters 11 and 13 that is, we need to know which position on the ring will be attacked to give the intermediate... 

As has been noted earlier, the solvent usually has little effect on free-radical substitutions in contrast to ionic ones indeed, reactions in solution are often quite similar in character to those in the gas phase, where there is no solvent at all. However, in certain cases the solvent can make an appreciable difference. Chlorination of 2,3-dimethylbutane in aliphatic solvents gave 60% (CH3)2CHCH-(CH3)CH2C1 and 40% (CH3)2CHCC1(CH3)2, while in aromatic solvents the ratio became 10 90. This result is attributed to complex formation between the... 

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. 

Aromatic nitro compounds undergo nucleophilic aromatic substitutions with various nucleophiles. In 1991 Terrier s book covered (1) SNAr reactions, mechanistic aspects (2) structure and reactivity of anionic o-complexes (3) synthetic aspects of intermolecular SNAr substitutions (4) intramolecular SNAr reactions (5) vicarious nucleophilic substitutions of hydrogen (VNS) (6) nucleophilic aromatic photo-substitutions and (7) radical nucleophilic aromatic substitutions. This chapter describes the recent development in synthetic application of SNAr and especially VNS. The environmentally friendly chemical processes are highly required in modem chemical industry. VNS reaction is an ideal process to introduce functional groups into aromatic rings because hydrogen can be substituted by nucleophiles without the need of metal catalysts. 

A comparative analysis of the kinetics of the reactions of atoms and radicals with paraffinic (R1 ), olefinic (R2H), and aromatic alkyl-substituted (R3H) hydrocarbons within the framework of the parabolic model permitted a new important conclusion. It was found that the tt-C—C bond occupying the a-position relative to the attacked C—H bond increases the activation energy for thermally neutral reaction [11]. The corresponding results are presented in Table 6.9. 

Nucleophilic substitution is the widely accepted reaction route for the photosubstitution of aromatic nitro compounds. There are three possible mechanisms11,12, namely (i) direct displacement (S/v2Ar ) (equation 9), (ii) electron transfer from the nucleophile to the excited aromatic substrate (SR wlAr ) (equation 10) and (iii) electron transfer from the excited aromatic compound to an appropriate electron acceptor, followed by attack of the nucleophile on the resultant aromatic radical cation (SRi w 1 Ar ) (equation 11). Substituent effects are important criteria for probing the reaction mechanisms. While the SR wlAr mechanism, which requires no substituent activation, is insensitive to substituent effects, both the S/v2Ar and the Sr+n lAr mechanisms show strong and opposite substituent effects. 

Anodic conversion of aromatics proceeds in most cases by le-transfer to the anode to form a radical cation (34) (Scheme 9). Oxidation is facilitated by extension of the 7T-system ( 1/2 vs. Ag/Ag+ benzene 2.08 V, pyrene 0.86 V) and by electron donating substituents ( 1/2 vs. Ag/Ag+p-phenylenediamine —0.15 V). Oxidation potentials of polycyclic aromatics and substituted benzenes are collected in Ref [140-142]. 

Benzylic CH bonds Benzylic CH bonds can be preferentially substituted at the anode by oxidation of the aromatic ring to a radical cation, which can undergo side-chain substitution at the benzylic carbon atom and/or nuclear substitution. Benzylic substitution preponderates, when there is an alkyl substituent at the aromatic carbon bearing the highest positive charge density in the radical cation, while a hydrogen at this position leads to a nuclear substitution [16]. Anodic benzylic substitution is used in technical processes for the conversion of alkyl aromatics into substituted benzaldehydes [17, 18]. Anodic benzylic substitution has been used for the regioselective methoxylation of estratrienone at C9 (Fig. 4) [19]. 

MILLER, J. Aromatic Nucleophilic Substitution (Elsevier, 1968). nonhebel, d. c. and walton, j. c. Free-radical Chemistry (CUP,... 

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