Aromatic substitution of benzene

Since benzenesulfonyl peroxide was used as an initiator in polymerization reactions, it was thought that a free radical aromatic substitution of benzene by the benzenesulfonoxy radical takes place. A detailed study by Dannley and Knipple reveals that attachment of the sulfonoxy group derived from a bis(arylsulfonyl) peroxide to the aromatic ring occurs by electrophilic aromatic substitution (equation 5) °. 

In the oxidative aromatic substitution of benzene with the nitrosonium cation (NO+), the benzene complex with symmetry 12 has been calculated as a local minimum at the B3LYP/6-31G(d) level of theory with an energy of 48 kcal mol-1 above that of the 7t-complex 13 <1999PCA4261> therefore, the former should not be relevant for the nitrosation mechanism as was previously proposed (Figure 3) <1985RJOC842>. 

Figure 3 Geometries of the local minimum 12 and of the (C6H5- -N0)+ 7r-complex 13 in the oxidative aromatic substitution of benzene with NO+ at the B3LYP/6-31 G(d) level.

Notice that the mechanism of the reaction is the same as the mechanism for electrophilic aromatic substitution of benzene (Section 19.3). 

The electron-withdrawing nitrogen atom makes the intermediate obtained from electrophilic aromatic substitution of pyridine less stable than the carbocation intermediate obtained from electrophilic aromatic substitution of benzene. Pyridine, therefore, is less reactive than benzene. Indeed, it is even less reactive than nitrobenzene. (Recall from Section 19.14 that an electron-withdrawing nitro group strongly deactivates a benzene ring toward electrophilic aromatic substitution.)... 

In Summary Naphthalene is activated with respect to electrophilic aromatic substitution favored attack takes place at Cl. Electrophilic attack on a substituted naphthalene takes place on an activated ring and away from a deactivated ring, with regioselectivity in accordance with the general rules developed for electrophilic aromatic substitution of benzene derivatives. Similar considerations apply to the higher polycyclic aromatic hydrocarbons. 

General mechanism for electrophilic aromatic substitution of benzene... 

Nucleophilic Substitutions of Benzene Derivatives. Benzene itself does not normally react with nucleophiles such as haUde ions, cyanide, hydroxide, or alkoxides (7). However, aromatic rings containing one or more electron-withdrawing groups, usually halogen, react with nucleophiles to give substitution products. An example of this type of reaction is the industrial conversion of chlorobenzene to phenol with sodium hydroxide at 400°C (8). 

We will return to the aromatic stabilization of benzene in more detail in Chapter 9, but substituted benzenes provide excellent examples of how proper use of the resonance concept can be valuable in predicting reactivity. Many substituents can be readily classified... 

Aromatic hydrocarbons, like paraffin hydrocarbons, react by substitution, but by a different reaction mechanism and under milder conditions. Aromatic compounds react by addition only under severe conditions. For example, electrophilic substitution of benzene using nitric acid produces nitrobenzene under normal conditions, while the addition of hydrogen to benzene occurs in presence of catalyst only under high pressure to... 

Certain groups attached to an aromatic ring can donate electrons into its delocalized molecular orbitals. Examples of these electron-donating substituents include —NH2 and —OH. Electrophilic substitution of benzene is much faster when an electron-donating substituent is present. For example, the nitration of phenol, C6H5OH, proceeds so quickly that it requires no catalyst. Moreover, when the products are analyzed, the only products are found to be 2-nitrophenol (ortho-nitrophenol, 37) and 4-nitrophenol (pnra-mtrophcnol, 38 . 

Aromatic rings are much less reactive than their double-bond character would suggest they commonly undergo substitution rather than addition. Electrophilic substitution of benzene with electron-donating substituents is accelerated and takes place at the ortho and para positions preferentially. Electrophilic substitution of benzene with electron-withdrawing substituents takes place at a reduced rate and primarily at the meta positions. 

Peroxide decomposition in aromatic and other unsaturated solvents homolytic aroniMic substitution and olefin polymerization Decomposition of peroxides in aromatic solvents leads to attack on the aromatic nucleus by radicals and hence to substitution products (for a recent summary, see Williams, 1970). In the substitution of benzene and related substrates by phenyl radicals, for example, cyclohexadienyl... 

In aromatic substitution of the electrophilic type, a cation or potential cation attacks the benzene ring. The transition state or intermediate, whichever it may be, has largely covalent bonds holding... 

Replacement of one of the benzene rings in a fenamic acid by pyridine interestingly leads to a compound which exhibits antihypertensive rather than antiinflammatory activity. Preparation of this agent starts with nucleophilic aromatic substitution of anthranilic acid (8) on 4-chloropyri-dine. The product (9) is converted to its acid chloride (10), and this is conden.sed with piperidine. There is thus obtained ofornine (11) [3]. 

Nucleophilic aromatic substitutions Pyridine is more reactive than benzene towards nucleophilic aromatic substitutions because of the presence of electron-withdrawing nitrogen in the ring. Nucleophilic aromatic substitutions of pyridine occur at C-2 (or C-6) and C-4 positions. 

Electrophilic aromatic substitution Electrophilic aromatic substitution of indole occurs on the five-membered pyrrole ring, because it is more reactive towards such reaction than a benzene ring. As an electron-rich heterocycle, indole undergoes electrophilic aromatic substitution primarily at C-3, for example bromination of indole. 

A priori, the two most likely mechanisms for electrophilic aromatic substitution on benzene, in the absence of strong base,156 are (1) direct displacement, the transition state for which is shown in 65, and (2) a two-step reaction in which... 

The aromatic silylation of benzene and substituted benzenes by Me3Si+ have been studied by several groups. In a high-pressure mass-spectrometric study, Stone and Stone144... 

Dinitration of p-chloro(trifluoromethyl)benzene will take place at the ring positions ortho to the chlorine. Compound A is 2-chloro-5-(trifluoromethyl)-l,3-dinitrobenzene. Trifluralin is formed by nucleophilic aromatic substitution of chlorine by dipropylamine. Trifluralin is N, A-dipropyl-4-(trifluoromethyl)-2,6-dinitroaniline. 

In another example of an electrophilic aromatic substitution reaction, benzene reacts with a mixture of concentrated nitric and sulfuric acids to create nitrobenzene. 

By far the most common methods for the preparation of dibenzoselenophenes and 2-benzoselenophenes, like the synthesis of 1-benzoselenophenes, rely upon the annulation of the heterocyclic ring system onto a preformed benzene ring and mostly involve the formation of one or two Se-C bonds as their key steps, with only a few exceptions [1, 119, 120], Intramolecular electrophilic aromatic substitution of biphenyl-2-yl trifluoromethylselenide to 5-(trifluoromethyl)dibenzoselenopheni um triflate (62) [99, 143] and synthesis of tetramethoxydibenzoselenophene (95) (Scheme 26) [144, 145] are examples. 

Nucleophilic aromatic substitution of the fluorine substituents by benzene-dithiolate sulfur atoms (step a), reduction of the nitro compound (step b), diazotization, reaction with KSaCOEt, alkaline hydrolysis, and acidification gave tpS4 H2 (step c). It could be purified via the [Ni(tpS4)]2 complex (Fig. 1), which is readily hydrolyzed with dilute hydrochloric acid to give pure tpS4 H2. 

For cleavage processes involving the loss of chloride ion, then, one might expect to find similarities to the regiochemistry that is observed in nucleophilic aromatic substitution. Assuming for the purpose of analysis that route (a) is predominant, one can use the rate data of Chambers et al. [34] to calculate the activating effects of chlorine vs. hydrogen in nucleophilic aromatic substitution in benzene systems (ortho meta para = 12.1 4.85.1.00) and then the relative rates for nucleophilic substitution (Chart I, numbers in parentheses). Note that the... 

A more interesting problem than the influence of substituents in the electrophilic reagent of azo coupling is the extremely high selectivity of the C-coupling reactions, relative to other electrophilic aromatic substitutions. Unsubstituted benzene does not react with any arenediazonium ion, 1,3,5-trimethoxybenzene reacts very slowly with strongly electrophilic diazonium ions only aromatic amines (e.g. N,N-dimethyl-aniline) or phenolate ions react very fast, in some cases close to diffusion control. 

Phosphinines are a special group of phosphaaUcenes in which the P=C double bond becomes integrated into the aromatic system of benzene and related arenes. The majority of examples are based on the mono-phospha-benzenes, but di-and triphospha-benzenes in various substitution patterns have also been employed as ligands. The coordination chemistry of this class of ligands has been reviewed. ... 

The electrophilic aromatic substitution of aryl halides takes place less readily than with benzene (electron-withdrawing effect), but occurs at the ortho and para positions (the lone pairs on the halogen assist in delocalizing the positive charge in the intermediate). Further chlorination of chlorobenzene, in the presence of aluminium or iron trichlorides, gives 1,4-dichlorobenzene and some 1,2-dichlorobenzene. Nitration normally occurs to give the 2- and 4-nitro- and 2,4-dinitrochlorobenzenes (Scheme 4.13). 

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