Electrophilic aromatic substitution of substituted benzenes

The net effect of electron donation and withdrawal on the reactions of substituted aromatics is discussed in Sections 18.7-18.9. 

SampI Probl6m 18.3 Classify each substituent as electron donating or electron withdrawing. 

Always look at the atom directly bonded to the benzene ring to determine electron-donating or electron-withdrawing effects. An O or N atom with a lone pair of electrons makes a substituent electron donating. A halogen or an atom with a partial positive charge makes a substituent electron withdrawing. 

An O atom with a lone pair bonded directly to the benzene ring I 

An atom with a partial (+) charge bondeo directly to the benzene ring 

Electrophilic aromatic substitution is a general reaction of all aromatic compounds, including polycyclic aromatic hydrocarbons, heterocycles, and substituted benzene derivatives. A substituent affects two aspects of electfophilic aromatic substitution  

Toluene (C6H5CH3) and nitrobenzene (C6H5NO2) illustrate two possible outcomes. 

Toluene reacts faster than benzene in all substitution reactions. Thus, its electron-donating CH3 group activates the benzene ring to electrophilic attack. Although three products are possible, compounds with the new group orlho or para to the CH3 group predominate. The CH3 group is therefore called an ortho, para director. 

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We begin with the basic features and mechanism of electrophilic aromatic substitution (Sections 18.1-18.5), the basic reaction of benzene. Next, we discuss the electrophilic aromatic substitution of substituted benzenes (Sections 18.6-18.12), and conclude with other useful reactions of benzene derivatives (Sections 18.13-18.14). The ability to interconvert resonance structures and evaluate their relative stabilities is crucial to understanding this material. 

Why Substituents Activate or Deactivate a Benzene Ring Figure 18.6 Energy diagrams comparing the rate of electrophilic aromatic substitution of substituted benzenes... 

To explain electrophilic aromatic substitution of substituted benzene derivatives, a generic benzene derivative, 61, is used in Figure 21.1, with a substituent X. This is used rather than a specific example in order to show the similarities and differences in reactivity for electron-releasing versus electron-withdrawing groups. The carbon of the benzene ring attached to the substituent is defined as the ipso carbon ( ) in Figure 21.1. There are only three possible arenium ion intermediates for the reaction of any monosubstituted benzene derivative 61 with an electrophile such as Br+ 62, 63, and 64. 

As expected for aromatic systems, the l-hetero-2,4-cyclopentadienes undergo electrophilic substitution. There are two sites of possible attack, at C2 and at C3. Which one should be more reactive An answer can be found by the same procedure used to predict the regiose-lectivity of electrophilic aromatic substitution of substituted benzenes (Chapter 16) enumeration of all the possible resonance forms for the two modes of reaction. 

Electrophilic addition reactions. See also Addition reactions with butylenes, 4 405-408 of maleic anhydride, 75 490 with methacrylic acid/derivatives, 76 236-237 of propylene, 20 774 Electrophilic aromatic substitution, benzene, 3 599-601 Electrophilic attack, at nitrogen and carbon, 27 98... 

The nitration, sulphonation and Friedel-Crafts acylation of aromatic compounds (e.g. benzene) are typical examples of electrophilic aromatic substitution. 

Nitration in sulphuric acid is a reaction for which the nature and concentrations of the electrophile, the nitronium ion, are well established. In these solutions compounds reacting one or two orders of magnitude faster than benzene do so at the rate of encounter of the aromatic molecules and the nitronium ion ( 2.5). If there were a connection between selectivity and reactivity in electrophilic aromatic substitutions, then electrophiles such as those operating in mercuration and Friedel-Crafts alkylation should be subject to control by encounter at a lower threshold of substrate reactivity than in nitration this does not appear to occur. 

In addition to benzene and naphthalene derivatives, heteroaromatic compounds such as ferrocene[232, furan, thiophene, selenophene[233,234], and cyclobutadiene iron carbonyl complexpSS] react with alkenes to give vinyl heterocydes. The ease of the reaction of styrene with sub.stituted benzenes to give stilbene derivatives 260 increases in the order benzene < naphthalene < ferrocene < furan. The effect of substituents in this reaction is similar to that in the electrophilic aromatic substitution reactions[236]. 

Reduction of arenes by catalytic hydrogenation was described m Section 114 A dif ferent method using Group I metals as reducing agents which gives 1 4 cyclohexadiene derivatives will be presented m Section 1111 Electrophilic aromatic substitution is the most important reaction type exhibited by benzene and its derivatives and constitutes the entire subject matter of Chapter 12... 

REPRESENTATIVE ELECTROPHILIC AROMATIC SUBSTITUTION REACTIONS OF BENZENE... 

The scope of electrophilic aromatic substitution is quite large both the aromatic com pound and the electrophilic reagent are capable of wide variation Indeed it is this breadth of scope that makes electrophilic aromatic substitution so important Elec trophilic aromatic substitution is the method by which substituted derivatives of benzene are prepared We can gam a feeling for these reactions by examining a few typical exam pies m which benzene is the substrate These examples are listed m Table 12 1 and each will be discussed m more detail m Sections 12 3 through 12 7 First however let us look at the general mechanism of electrophilic aromatic substitution... 

Representative Electrophilic Aromatic Substitution Reactions of Benzene... 

With this as background let us now examine each of the electrophilic aromatic substitution reactions presented m Table 12 1 m more detail especially with respect to the electrophile that attacks benzene... 

Now that we ve outlined the general mechanism for electrophilic aromatic substitution we need only identify the specific electrophile m the nitration of benzene to have a fairly clear idea of how the reaction occurs... 

Figure 12 3 adapts the general mechanism of electrophilic aromatic substitution to the nitration of benzene The first step is rate determining m it benzene reacts with nitro mum ion to give the cyclohexadienyl cation intermediate In the second step the aro maticity of the ring is restored by loss of a proton from the cyclohexadienyl cation... 

Complexation of bromine with iron(III) bromide makes bromine more elec trophilic and it attacks benzene to give a cyclohexadienyl intermediate as shown m step 1 of the mechanism (Figure 12 6) In step 2 as m nitration and sulfonation loss of a proton from the cyclohexadienyl cation is rapid and gives the product of electrophilic aromatic substitution... 

Turning now to electrophilic aromatic substitution in (trifluoromethyl)benzene we con sider the electronic properties of a trifluoromethyl group Because of their high elec tronegativity the three fluorine atoms polarize the electron distribution m their ct bonds to carbon so that carbon bears a partial positive charge... 

Oxygen stabilized carbocations of this type are far more stable than tertiary carbocations They are best represented by structures m which the positive charge is on oxygen because all the atoms have octets of electrons m such a structure Their stability permits them to be formed rapidly resulting m rates of electrophilic aromatic substitution that are much faster than that of benzene... 

Because the carbon atom attached to the ring is positively polarized a carbonyl group behaves m much the same way as a trifluoromethyl group and destabilizes all the cyclo hexadienyl cation intermediates m electrophilic aromatic substitution reactions Attack at any nng position m benzaldehyde is slower than attack m benzene The intermediates for ortho and para substitution are particularly unstable because each has a resonance structure m which there is a positive charge on the carbon that bears the electron withdrawing substituent The intermediate for meta substitution avoids this unfavorable juxtaposition of positive charges is not as unstable and gives rise to most of the product... 

Polycyclic aromatic hydrocarbons undergo electrophilic aromatic substitution when treated with the same reagents that react with benzene In general polycyclic aromatic hydrocarbons are more reactive than benzene Most lack the symmetry of benzene how ever and mixtures of products may be formed even on monosubstitution Among poly cyclic aromatic hydrocarbons we will discuss only naphthalene and that only briefly Two sites are available for substitution m naphthalene C 1 and C 2 C 1 being normally the preferred site of electrophilic attack... 

Section 12 17 Polycyclic aromatic hydrocarbons undergo the same kind of electrophilic aromatic substitution reactions as benzene... 

Partial rate factor (Section 12 10) In electrophilic aromatic substitution a number that compares the rate of attack at a particular nng carbon with the rate of attack at a single po sition of benzene... 

Other matters that are important include the ability of the electrophile to select among the alternative positions on a substituted aromatic ring. The relative reactivity of different substituted benzenes toward various electrophiles has also been important in developing a firm understanding of electrophilic aromatic substitution. The next section considers some of the structure-reactivity relationships that have proven to be informative. 

The polycyclic aromatic hydrocarbons such as naphthalene, anthracene, and phenan-threne undergo electrophilic aromatic substitution and are generally more reactive than benzene. One reason is that the activation energy for formation of the c-complex is lower than for benzene because more of the initial resonance stabilization is retained in intermediates that have a fused benzene ring. 

The table below gives first-order rate constants for reaction of substituted benzenes with w-nitrobenzenesulfonyl peroxide. From these data, calculate the overall relative reactivity and partial rate factors. Does this reaction fit the pattern of an electrophilic aromatic substitution If so, does the active electrophile exhibit low, moderate, or high substrate and position selectivity ... 

Because of Us high polarity and low nucleophilicity, a trifluoroacetic acid medium is usually used for the investigation of such carbocationic processes as solvolysis, protonation of alkenes, skeletal rearrangements, and hydride shifts [22-24] It also has been used for several synthetically useful reachons, such as electrophilic aromatic substitution [25], reductions [26, 27], and oxidations [28] Trifluoroacetic acid is a good medium for the nitration of aromatic compounds Nitration of benzene or toluene with sodium nitrate in trifluoroacetic acid is almost quantitative after 4 h at room temperature [25] Under these conditions, toluene gives the usual mixture of mononitrotoluenes in an o m p ratio of 61 6 2 6 35 8 A trifluoroacetic acid medium can be used for the reduction of acids, ketones, and alcohols with sodium borohydnde [26] or triethylsilane [27] Diary Iketones are smoothly reduced by sodium borohydnde in trifluoroacetic acid to diarylmethanes (equation 13)... 

Nitration by electrophilic aromatic substitution is not limited to benzene alone, but is a general reaction of compounds that contain a benzene ring. It would be a good idea to write out the answer to the following problem to ensure that you understand the relationship of starting materials to products in aromatic nitration before continuing to the next section. 

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