8. Aromatic Substitution – Advanced Organic Chemistry


Aromatic Substitution


By the end of this chapter you should be familiar with

  • The mechanism of electrophilic aromatic substitution.
  • How a variety of substituents can be substituted into the benzene ring.
  • The effects of substituents on orientation and reactivity, activation and deactivation.
  • The mechanism of nucleophilic substitution in aromatic systems.

Substitution reactions at an aliphatic carbon are generally nucleophilic. In aromatic systems the situation is reversed. Three types of reagents can perform substitution in aromatic compounds, that is, electrophiles, nucleophiles and free radicals. In this chapter, we will deal with electrophilic and nucleophilic substitutions; the substitution brought about by radicals has been discussed in free radicals. Benzene is a planar symmetrical hexagon with six trigonal (sp2) carbon atoms, each having one hydrogen atom in the plane of the ring. All the bond lengths are 1.39 Å and all the 13C shifts are the same. We know that the principal reaction of benzene and its derivatives is substitution rather than addition. It combines only with very reactive electrophiles. Indeed, electrophilic substitution in aromatic systems is one of the most important reactions in chemistry and has many commercial applications.

The π-electron cloud above and below the plane of the benzene ring is a source of electron density and confers nucleophilic properties on the system. Thus, reagents that are deficient in electron density (electrophiles) are likely to attack, but electron-rich nucleophiles should be repelled and, therefore, are unlikely to react. Furthermore, in electrophilic substitution the leaving group is a proton (H+), but in nucleophilic substitution it is a hydride ion (H); the former process is energetically more favourable. In fact, nucleophilic aromatic substitution is not common, but it does occur in certain circumstances.

The carbocation generated by the addition of an electrophile to an alkene is destroyed in the second step by the addition of a nucleophilic species. Both carbon atoms become sp3 and the double bond is lost. A similar second step in aromatic molecules would result in destruction of the resonance-stabilized system and, therefore, does not occur.


In simple terms, electrophilic aromatic substitution proceeds in two steps. Initially, the electrophile, E+, adds to a carbon atom of the benzene ring in the same manner as it reacts with an alkene, but here the π-electron cloud is disrupted, in the process giving the cationic species (arenium ion or substituted cyclohexadienyl cation). The cationic intermediate is, of course, less stable than the starting material, but as a cation it is reasonably stable because of delocalization around the six-member ring. However, in the second step, the resultant carbocation eliminates a proton to regenerate the aromatic system. This step is quite exothermic. The combined processes of addition and elimination result in overall substitution.

The reaction has been considered to proceed via the formation of a complex as an intermediate. Two types of such complexes have been discussed as probable intermediates. The first is σ-complex and the second is π-complex. The intermediate carbocation is stabilized by resonance, with the positive charge shared formally by three carbon atoms of the benzene ring. The resonance hybrid structure A indicates the delocalization of the charge. The carbocation is also referred to as a σ-complex or Wheland intermediate or benzenonium ion in which an electrophile is bonded tetrahedrally to a carbon atom of the aromatic ring.

The hybridization state of the carbon atom that is attacked changes from sp2 to sp3 and the planar aromatic system is destroyed. Wheland complexes are high-energy intermediates devoid of conjugated aromatic electron sextet present in the product and in the starting material. Consequently, the formation of these complexes is the rate-determining step of the reactions. In the second step, a proton is abstracted by a basic species present in the reaction mixture. The attacked carbon atom reverts to sp2 hybridization, and planarity and aromaticity are restored. This fast step is energetically favourable and is regarded as the driving force for the overall process.

The π-complex involves a weak interaction between the π-electrons of the ring and the electrophile. In this case, there is no definite bond formation with the ring carbon atom and only the inductive effects of the substituents present on the aromatic ring stabilize the complex. These complexes have not been isolated but their existence has been proved from changes in the UV spectra. The well known silver ion-olefin adduct has been classified as a π-complex.

The energy changes that occur during the course of the reaction are related to the structural changes in the reaction profile shown in the following figure. It should be noted that each step proceeds through a high-energy transition state in which partial bonds attach the electrophile and the proton to the ring and the π-cloud is incomplete.

Figure 8.1 Energy profile for the electrophilic attack on benzene

Most examples of electrophilic aromatic substitution proceed by this sequence of events:

  • Generation of an electrophile
  • Attack of the aromatic ring on the electrophile
  • The resulting carbocation is stabilized by resonance
  • A proton is eliminated from the carbocation, regenerating the π-cloud
  • A substituted aromatic compound is formed

The product is a substituted benzene derivative. The position around the benzene ring relative to any substituent is named as follows:

The cationic intermediate can be trapped using nonnucleophilic and nonbasic counter ion, such as SbF6. In this octahedral anion, the fluorine atoms surround the central antimony atom and the negative charge is spread over all seven atoms. The protonation is carried out using FSO3H and SbF5 at −120°C.

In some instances, the Wheland intermediate can be isolated. For example, when hexamethyl benzene is treated with the nitrating agent nitronium fluoroborate (NO2+ BF4), the product cannot undergo proton loss and can be isolated at −70°C.

Olah and coworkers have shown that benzotrifluoride-nitryl fluoride-boron trifluoride system forms a yellow salt (I) that is stable upto −15°C and the mesitylene-ethylfluoride-boron trifluoride system form an orange salt (II), which melts at −15°C.

In the following sections, various examples are reviewed, highlighting the source of the electrophile and any variations in mechanistic detail.

8.2.1 Nitration of Benzene

Introduction of nitro group into an aromatic system provides a general entry into aromatic nitrogen compounds. Among electrophilic substitutions, nitration is perhaps the most widely studied. Benzene cannot be nitrated using nitric acid alone, which lacks a strong electrophilic centre, but it is readily achieved using a mixture of concentrated nitric acid and concentrated sulphuric acid, the so-called ‘mixed acid’. The product is nitrobenzene. The interaction of nitric acid and sulphuric acid produces the electrophile, the nitronium ion (NO2+), which is linear with sp hybridized nitrogen at the centre. It is isoelectronic with CO2. The sulphuric acid is also the source of the base HSO4 that removes the proton in the second step.

Other nitrating agents that have been mentioned in the literature are NO2+ BF4, NO2+ClO4, CH3COONO2, arylchloroformates and silver nitrate. Nitration is largely dependent on the reaction conditions and the nature of the substrate. Deactivated compounds such as nitrobenzene or benzoic acid exhibit second order kinetics, that is, the activated complex contains a molecule each of the aromatic and the NO2+ ion. The nitration of compounds that are less reactive than benzene such as ethyl benzoate or p–dichlorobenzene obeys a pseudo first order kinetics, the rate being dependent on the concentration of the substrate only. Compounds more reactive than benzene such as toluene or xylene show a zero order kinetics, that is, the rate is independent of the substrate.

8.2.2 Halogenation of Benzene

Halogen molecules (molecular Cl2 or Br2) are not strong electrophiles and do not react with benzene. However, in the presence of a Lewis acid, (a Lewis acid is a species that accepts an electron-pair and Lewis base donates an electron-pair) reaction occurs readily. The role of the catalyst is to accept a lone pair of electrons from the halogen molecule; this weakens the X-X bond (X = Cl or Br), which then becomes electron-deficient at one of the halogen atoms. The catalyst is referred to as halogen carrier. The actual electrophile is probably the complex formed from the halogen and the catalyst, rather than a halonium ion, for example, Cl+ or Br+. Bromination of benzene serves as a good example of halogenation. Hydrated Lewis acids are inactive as catalysts, so they are generally generated in situ to prevent hydration.

Fluorination with F2 itself is too vigorous to be of preparative value, as it results in a breakdown of the molecules being attacked. Aryl fluorides can be prepared by heating aryl diazonium tetrafluoroborates, which are prepared by the reaction of an arylamine with NaNO2 and fluoroboric acid, HBF4.

During the reaction of I2 and FeI3 with benzene, the equilibrium favours the starting materials and the aryl iodide is not obtained. Iodine itself is not reactive enough to attack benzene, even with the assistance of a catalyst, but will attack more reactive aromatic species. Direct iodination is difficult since iodine is the least active of the halogens. Electrophilic iodine (I+) is obtained by oxidizing I2 with an oxidizing agent such as nitric acid or mercuric oxide.

8.2.3 Friedel–Crafts Alkylation

Charles Friedel (1832–1899), a French chemist, and James Crafts (1839–1917), an American mining engineer, both studied with Wurtz and then worked together in Paris, and in 1887 they discovered the Friedel–Crafts reaction. Alkyl halides require a Lewis acid catalyst to accentuate the polarization and create a more powerful electrophile. There is not enough positive character on the carbon atom in alkyl halides for them to react with benzene; the catalyst increases the positive character. Aluminium chloride is commonly used as the Lewis acid, accepting a pair of electrons from the halogen atom. Other commonly used catalysts are AlBr3, BF3, GaBr3 and TiCl4, etc. The electrophile may be a carbocation or perhaps more likely the complex shown. An alkyl benzene is produced.

In the reaction of benzene with 1-chlorobutane, where rearrangement converts a primary carbocation into a secondary carbocation, 65% of the product is the rearranged product.

Of course, rearrangement of the alkyl group is not a problem if the alkyl group is not rearrangement prone, as in the following example.

Another complication in Friedel-Crafts alkylation is that alkyl benzene products are more reactive than benzene itself. This means that the product itself can undergo alkylation, and a mixture of products is observed.

The monoalkylated product can be obtained in good yield, however, if a large excess of the starting material is used.

8.2.4 Friedel–Crafts Acylation

Acylation can be achieved using either acyl halides or acid anhydrides. The product is a ketone. Acyl halides are more reactive than the anhydrides, but still require a Lewis acid catalyst to promote the reaction. The attacking species is the resonance-stabilized acylium ion or the complex. Because the product of a Friedel–Crafts acylation reaction contains a carbonyl group that can complex with AlCl3, it must be carried out with more than one equivalent of AlCl3. When the reaction is over, water is added to the reaction mixture to liberate the product from the complex by hydrolyzing the aluminum salts. Acylation is better than alkylation. Indeed, alkylation is often carried out not directly, but via initial acylation followed by reduction of the acylated product. For example, ethyl benzene can be prepared by acylation of benzene with acetyl chloride followed by reduction.

Solvents affect the distribution of products in the Fridel–Crafts acylation. For example, the acylation of anthracene in CS2 gives 9-acetylanthracene as the main product, whereas 1–acetylanthracene is obtained in nitrobenzene. The explanation may be given that the CH3COCl−AlCl3 complex solvolyzed by nitrobenzene is bulkier than in CS2; therefore, its attack at 1–position is favoured.

8.2.5 Sulphonation of Benzene

Benzene itself reacts very slowly or is not attacked by concentrated sulphuric acid, but is readily converted to benzenesulphonic acid by fuming sulphuric acid. This is a solution of 10–30% sulphur trioxide in concentrated sulphuric acid, and is known as oleum. Note here that the attacking electrophile is a neutral species and that the electron-deficient sulphur atom of SO3 is the electrophilic centre. Other reagents that form carbon–sulphur bonds are fluorosulphuric acid (FSO3H), chlorosulphuric acid (ClSO3H) and sulphurtrioxide (SO3). Sulphonation of benzene is a reversible reaction. If benzenesulphonic acid is heated in dilute acid, the reaction proceeds in a reverse direction.

The distribution of isomers in the products of sulphonation depends on the temperature of the reaction and the concentration of the acid. Sulphonation of naphthalene forms 1-sulphonic acids between 0−40°C in 90% yields, but at 160°C the 2-isomer is obtained in about the same yield. Sulphonation differs from the other examples that have been discussed in that it can readily be reversed. Heating benzenesulphonic acid with dilute sulphuric acid or water converts it back to benzene.

Because sulphonation is reversible, a sulphonic acid group is sometimes introduced to occupy a position on the ring, temporarily protecting that position from attack by another electrophile. Sulphonation is also a useful way of directing further substitution to a specific position.

8.2.6 Protonation

Although benzene is a very weak base, it is protonated in concentrated sulphuric acid to a very slight extent. This reaction can be detected if the protonating mixture contains deuterium or tritium, the isotopes of hydrogen, since isotope exchange takes place. Some deuteriated benzene is produced when benzene is treated with D2SO4, and this can be detected by mass spectrometry and NMR spectroscopy. The more deuterium there is in the protonation mixture, the more exchange occurs. Notice that the regeneration of the aromatic system occurs by elimination of a proton.


In benzene, the six hydrogen atoms are chemically equivalent and an electrophilic attack would give rise to a single product only. But if a group is already present on the ring, the hydrogens become non-equivalent and the incoming electrophile can attack either the ortho, meta or para positions to yield a mixture of products. It is believed that electrophiles have a tendency to attack a position of high electron density. The substituent can thus cause the compound to react faster or slower than benzene itself.

Two experimental observations illustrate that the behaviour is quite varied. The rate of nitration of toluene is appreciably faster than that of benzene and produces a mixture of 2- and 4-nitrotoluenes. On the other hand, the nitration of nitrobenzene is more difficult than that of benzene and gives just one product, 1,3-dinitrobenzene.

A substituent in a benzene ring, therefore, influences the course of electrophilic substitution in two ways:

  • It affects the reactivity of the molecule
  • It controls the orientation of attack, that is, it controls which isomer is formed

The orientation and reactivity effects of each group are explained on the basis of resonance and field effects on the stability of the intermediate arenium ion. It is important to understand why this should happen. In the examples given earlier, the two substituents, the methyl group and the nitro group, exhibit different electronic behaviour. The methyl group is an electron donor and so increases the electron density of the ring. The nitro group is an electron acceptor and withdraws electron density from the ring.

These properties influence the course of the reactions of aromatic compounds with electrophiles. An electron-releasing group increases the electron density of the benzene ring, promoting electrophilic attack. Such substituents are known as activating groups. An electron-withdrawing group is deactivating and reduces the electron density of the ring, making attack by the electron-deficient reagent more difficult.

Both types of substituents affect the electron density at all positions of the ring, but exert their greatest effects at the ortho and para positions, making these sites the most electron rich in the case of donor groups and most electron-deficient when electron-withdrawing groups are present. Donor groups therefore direct attack of the electrophile to the ortho and para positions and are known as ortho/para directors (for example, CH3, OH, OR, NH2, NR2, NHCOCH3, X, etc). Conversely, aromatic compounds containing electron acceptor groups are attacked at the meta position, as this is the least electron-deficient site. Such groups are called meta directors (for example, +NR3, NO2, CHO, RCO, CO2H, CO2R, SO3H, CN, CF3, etc). Not all substituents fit exactly into this picture: halogens are deactivating but direct attack to the ortho and para positions.

  • Electron-donating substituents activate the benzene ring to electrophilic attack, which results in the formation of the ortho- and para-disubstituted benzene derivatives.
  • Electron-withdrawing substituents deactivate the ring to attack by electrophiles, which occurs at the meto-position.

Substituents exert their influence on a molecule through either the σ-bonds or the π-bonding system, in other words, by inductive and mesomeric (resonance) effects, respectively. The interaction influences both the electron density at the various ring positions and stability of the intermediate carbocation. The outcome can be understood by superimposing the electronic effects of the substituents on the slow, rate-determining step of the aromatic substitution discussed above.

In a σ-bond between two atoms of differing electronegativities, there is an unequal sharing of the electron-pair, with the electrons being attracted towards the more electronegative atom. This causes a permanent polarization of the molecule. This influence of an atom or group on the distribution of the electron-pair is called the inductive effect. Inductive effects rapidly die away along a saturated carbon chain. Substituents in an aromatic ring that withdraw electrons in this way exert a −I effect. They include not only halogens, the hydroxyl and nitro groups, where an electronegative atom is attached to the ring, but also groups such as carbonyl and nitrile, in which an electron-deficient carbon atom is bonded to the ring. Alkyl groups behave in the opposite manner, exerting a +I effect and releasing electron-density to the ring.

The mesomeric effect is the analogous redistribution of electrons in π-bonds. However, this resonance effect is transmitted throughout the whole of a conjugated system and creates alternate polarity at the carbon atoms along the system. Substituents that withdraw electron density in this way (−M groups) include carbonyl and nitro groups, whilst electron-releasing (+M) functions include amino and hydroxy groups.

Note that some groups can withdraw electrons by one of the two effects but release electrons by the other, although one of the effects usually predominates. Fluorine has a weaker +M and −I effect than oxygen. Both the +M and −I effects of the halogens fall in the order, F > Cl > Br > I, and the resultant effect leads to the order, F ~ H > Cl ~ Br ~ I. The ortho positions of all four halobenzenes are less reactive than the para positions and the meta positions are strongly deactivated.


Groups in which the atom attached to the benzene ring possesses a lone pair of electrons can interact with the aromatic ring, promoting ortho and para attack. The ring becomes more electron rich and, so, the reaction with electrophiles is facilitated.

In order to assess the influence that substituents have on the reactivity of aromatic molecules, it is important to consider their effects not only on the benzene ring itself, but also on the carbocation intermediates resulting from electrophilic attack. These species are relatively unstable and any feature that affects their stability will influence their ease of formation, and, therefore, the outcome of a reaction. We can illustrate the latter point by examining the attack by an electrophile E+ on methoxybenzene (anisole) at the three possible sites of attack.

Consider first the attack at the ortho position. Structure I has a positive charge located on the carbon atom to which the methoxy group is bonded. Notice that this is a tertiary carbocation, a species that is recognized as being particularly stable (remember nucleophilic aliphatic substitution reactions). An additional canonical structure can be drawn, involving donation of the lone pair of electrons on the oxygen atom to the electron-deficient C+. This fourth canonical form confers extra stability on the intermediate and lowers the energy of the transition state leading to it. An oxonium species such as II is more stable than a carbocation, for example, I, and, hence, can be considered to contribute more to the resonance hybrid.

A similar situation arises with species III associated with attack at the 4-position, and this carbocation intermediate, therefore, is also additionally stabilized by IV. However, no such structure can be drawn following meta attack and so the cation derived from this mode of attack is not additionally stabilized.

The consequences of the involvement of the methoxy group are to stabilize especially the carbocations arising from ortho and para attack and to lower the energy of activation for their formation. Notice that even attack at the meta position has lower activation energy than does benzene.

It should, therefore, be no surprise that the nitration of methoxybenzene is easier and faster than that of benzene and yields essentially only the 1,2- and 1,4-isomers (in almost equal amounts). Less than 1% of 3-nitroanisole is formed. Other electrophilic reactions follow this pattern. Hydroxy and amino groups behave like a methoxy group. Phenoxides, in which the oxygen carries a full negative charge, are especially activated towards electrophilic attack.

The negative end of the dipole of chlorobenzene is on the chlorine atom, whereas in methoxybenzene, the oxygen atom is the positive end of the dipole, supporting the view that overall a halogen is an electron-withdrawing substituent.

Halogen atoms also fall into this category. Possessing a lone pair of electrons, they are able to stabilize the intermediate cation arising from ortho/para attack. However, the halogenobenzenes behave differently from methoxybenzene and aniline in that the reaction with electrophiles is slower than for benzene. The nitration of chlorobenzene is about 30 times slower than that of benzene. Halogens are weakly deactivating substituents and yet are ortho/para directors. The halogens withdraw electrons inductively more strongly than they donate electrons by the mesomeric effect, with the result that the three intermediates from ortho, meta and para attack are all less stable than that arising from electrophilic attack of benzene. Nonetheless, ortho/para attack is still favoured because of the additional stabilization of the cations from the resonance forms.

Benzene reacts with bromine in the presence of catalysts only, while phenol reacts rapidly without a catalyst with bromine to give a white precipitate of 2,4,6-tribromophenol. The difference in reactivity is due to the enol nature of phenol.

The phenoxide ion is even more reactive towards electrophilic attack than phenol. It reacts with weak electrophiles as carbon dioxide. This reaction, known as the Kolbe-Schmidt process, is used industrially to prepare salicylic acid, a precursor in making aspirin.


Substituents that fall into this category include NO2, CO2R, COR, CN and SO3R. All are characterized by the atom attached to the ring being linked to a more electronegative atom by a multiple bond, and may be represented by X=Y, where Y is more electronegative than X. Electrons are therefore attracted towards Y, making X more electron-deficient and, therefore, more strongly electron-withdrawing. Formally, a positive charge is placed on the ortho and para positions.

The following substituents decrease the stability of the intermediate arenium ion and thus are deactivating substituents.

Electrophilic attack on compounds, which contain a substituent that withdraws electrons from the ring, always leads to the 3-substituted compound, with very little yield of the 2- and 4-isomers being formed. The reaction is more difficult than for benzene, in keeping with the reduced electron density at the ring carbon atoms.

Again, it is important to examine the intermediates formed by attack of an electrophile, E+, at the ortho, meta and para positions. This time, nitrobenzene will be used as the substrate. It should be noticed that in the structures V and VI, associated with ortho and para attack, a positive charge is placed on the carbon to which the substituent is attached. The resulting situation is destabilizing because positive charges are located on adjacent atoms.

While attack at the 3-position is still much slower than for benzene, no canonical form places positive charges on adjacent atoms, and so the intermediate is less destabilized than those arising from ortho and para attack. Hence, meta attack is the preferred reaction. For example, nitration of nitrobenzene gives 88% of 1,3-dinitrobenzene and only 8% and 1% of the 1,2- and 1,4-isomers, respectively. The reaction occurs at a relative rate of 6 × 10−8 to that of benzene.


Withdrawal of electrons through a σ bond is called inductive electron withdrawal. Groups such as trifluoromethyl (CF3), trialkylammonium (R3N+), PMe3+ and AsMe3+ are unable to interact with the π-system, but withdraw electrons as a result of the electronegativity of the fluorine atoms and the positively charged nitrogen, phosphorus and arsenic, respectively. A study of the canonical forms for electrophilic attack at the three sites indicates a situation similar to that discussed above for mesomerically withdrawing groups. The intermediates are overall destabilized by electron withdrawal, but structures VII and VIII are particularly unfavourable because the positive charge is adjacent to the electron-deficient atom of the substituent. Thus, attack occurs preferentially at the 3-position (meta), but is more difficult than electrophilic attack on benzene.


It is well known that, in comparison to hydrogen, alkyl groups donate electrons. It is therefore to be expected that toluene and other alkyl benzenes will react with electrophiles rather more easily than benzene. This is certainly the case, with toluene reacting with mixed acid at room temperature.

The canonical forms that contribute to the structure of the intermediate carbocation are shown here. Once again, one contributing form derived from attack at the 2- and the 4-positions has the positive charge located on the carbon atom to which the substituent is attached. It is noted that these structures, IX and X, are tertiary carbocations and that they are further stabilized by delocalization of the charge onto the methyl group, which, therefore, shares some of the electron deficiency. No such benefit results from attack at the 3-position, which is therefore not a favoured site for reaction. Nitration of toluene occurs about 25 times faster than that of benzene under similar conditions. It leads to a 2:1 mixture of 2- and 4-nitrotoluenes; only about 5% of the product is the 3-isomer (remember there are two ortho positions but only one para position).

The more efficient the alkyl group is at releasing electrons, the greater is the stabilization of the intermediate carbocation and the rate of electrophilic attack. Thus, tert-butylbenzene is nitrated faster than toluene.

This picture is somewhat generalized, since there are some exceptions. For instance, the chlorination of toluene proceeds faster than that of tert-butylbenzene. Hyperconjugation is at a maximum for a methyl group and has been offered as an explanation for these anomalies. (Hyperconjugation is a stabilizing interaction between a C–H bond and an adjacent σ-bond). For example, propene may be regarded as a resonance hybrid of two canonical forms. The stability of carbocations increases along the series. The increasing number of electron-releasing methyl groups attached to the carbocation centre helps to spread the positive charge more effectively.


It is expected that in monosubstituted benzene if the substituent is ortho, para–directing, the ortho to pora ratio should be 2:1. But usually in ortho, para-directing systems, the ortho substitution occurs to lesser extent than expected. This difference may be due to many factors, that is, polar effects of the substituent, solvent, temperature, size of the substituent, and the entering group (steric factors). The last two factors play a dominant role in determining the ortho to para ratios.

The relative proportion of ortho-product decreases, that is, the ortho/para ratio falls off sharply as the size of both the substituent Y and the attacking electrophile E+ increases, as a result of steric hindrance to ortho-substitution.

The size is not the sole consideration in determining o-/p-ratio. This fact is demonstrated by the nitration of the four halogenobenzenes.

This reversal, compared with the effect of the four alkyl groups shown here, stems from the fact that the alkyl groups differ very little in polarity from CH3 to Me3C, whereas the difference in polarity from F to I is marked indeed, F being very much more powerfully electron–withdrawing than I. Such electron withdrawal from the benzene ring will serve to inhibit attack by NO2+, and this effect will be exerted to a greater extent on the ortho–positions, adjacent to Y, than on the much more distant para–position. This polar effect dominates over the steric effect that will be operating in the opposite direction. The para–position in tert–butylbenzene is more reactive than that in toluene in nitration but less reactive in chlorination. It is believed that although the tert–butyl group stabilizes the positively charged transition state more effectively than methyl, it hinders the stabilizing solvation of the positively polarized ring carbon atom adjacent to it more strongly than does the smaller methyl group.

The electrophilic sulphonation of t-butyl benzene produces almost exclusively para product because the bulky alkyl group effectively blocks ortho attack. Thus, electronic factors favour ortho and para attack, and steric hindrance further favours para substitution.

A classic example of the steric factor dominating in electrophilic substitutions is p-cymene. From electronic considerations, the substitutions should be expected to occur at the position ortho to isopropyl group, but invariably, it takes place ortho to the methyl group.

But sometimes, because of the chemical interaction between the substituent and the electrophile, the ortho to para ratio becomes abnormally high. For example, nitration of anisole with the conventional nitrating mixture, where the nitrating agent is NO2+, gives ortho– and para–nitroanisoles in the ratio 31: 67. But when the same reaction is carried out with N2O5 (HNO3−Ac2O) this ratio becomes 71:28. This has been ascribed to the following mechanism:


In general, the effects of two substituents on the orientation and rate of electrophilic substitution are additive. The best product selectivity occurs when the two substituents are working together, but, unfortunately, this is not always the case. In general, resonance effects take predominance over inductive effects. There are several guiding principles that help to decide the product in less obvious cases:

  • Strongly activating groups dominate all other substituents
  • Weakly activating groups next take control of orientation
  • Deactivating groups exert the least control
  • Steric effects often play a part in deciding the outcome of a reaction

If one substituent is activating while the other is deactivating, mainly the activating group will direct the position of the entering group. When devising a synthesis of a particular compound (the target molecule), the effects of substituents have to be taken into account. It is essential to introduce substituents in the correct order, so that their directing influence assists the synthesis rather than hinders it. Remember:

  • ortho/para directors give mixtures of two isomers that can usually be separated
  • meta directors give only the meta isomer
  • ortho/para–directing groups always overcome the influence of meta directors
  • strongly electron-withdrawing groups may prevent electrophilic attack

In o-methylanisole, substitution is directed by the strongly activating −OCH3 group to the ortho and para positions, rather than being directed by the more weakly activating methyl group.

In p-acetamidotoluene, the acetamido group activates ortho positions and slightly deactivates meta–positions, whereas the methyl group activates ortho less strongly than acetamido. Consequently, the position that is ortho to acetamido and meta to methyl is more reactive than the position that is meta to acetamido and ortho to methyl.

If a meta–directing group is situated meta to an ortho/para–directing group, the substitution takes place ortho to the meta–directing group, rather than para.

The three xylenes (dimethylbenzenes) do not undergo electrophilic aromatic substitution at the same rate. Indeed, meta-xylene undergoes chlorination 200 times faster than para-xylene and 100 times faster than ortho-xylene. The differences in rates can be explained with the help of resonance structures for each of the intermediate arenium ions.

Polycyclic aromatic hydrocarbons are more reactive than benzene towards electrophilic substitution because delocalization of positive charge in the transition states is increased by the fusion of two or more benzene rings, although not all ring positions of the parent hydrocarbon are equivalent.

Nitration of naphthalene occurs almost exclusively in the 1- or α-position. Consideration of the contributing structures to the hybrid carbocation indicates why this is so. The resonance structures for the σ-complexes for α- and ß-attack may be represented as follows:

It is therefore expected from the above structures that the benzene ring is preserved in two structures for attack at the 1-position but in only one structure for attack at the 2-position. Thus, carbocation produced during α-attack is more stable than that formed from ß-attack and, hence, the rate of reaction at the α-position is significantly faster. The electrophilic attack, therefore, takes place at the 1-position. In a typical nitration reaction, the partial rate factors for 1- and 2- substitution are 470 and 50, respectively. A reaction, which gives only one of several possible isomers, is said to be regioselective.

There are, however, two conditions in which substitution occurs predominantly at 2-position. One applies when the reaction is thermodynamically controlled, as in sulphonation at higher temperatures because the 1-derivative, in which there is a steric repulsion between the substituent and the peri-hydrogen atom is thermodynamically less stable.

The presence of an electron-withdrawing group in naphthalene reduces the reactivity and causes substitution to occur in the unsubstituted ring, mainly at the 5- and 8-positions (that is, the two 1-positions of the ring). An electron-releasing group activates the molecule further and reaction occurs in the substituted ring. If the group is in the 1-position, substitution occurs at the 2- and 4-positions (that is, ortho and para to the electron-releasing group), but a 2-substituent directs almost entirely to the 1-position, although the 3-position is also an ortho position. The stabilization of the transition state in 1-position is more effective than when it is in 3-position.

The reactivities of polycyclic hydrocarbons follow from the principles described for naphthalene. The most reactive position in nitration for some polycyclic hydrocarbons are shown below.

Biphenyl is activated in the ortho and para positions and weakly deactivated in the meta–position. Electrophilic substitution in the biphenyl ring occurs at ortho/para positions because of increased delocalization of the positive charge into the second ring. The introduction of an electron-withdrawing group into biphenyl decreases the reactivity of the molecule and the substitution takes place in the unsubstituted ring. Electron-donating groups have the opposite effects.

The resonance effects also apply for electrophilic substitution in heterocyclic ring systems. The five-member ring systems are very reactive and the order of reactivity has been determined to be pyrrole > furan > thiophene > benzene. Pyrrole is highly reactive at both the 2- and 3-positions due to stabilization of positive charge by nitrogen. One difficulty in dealing with pyrrole is that it is readily converted into the trimer by acid. The presence of heteroatoms in the ring leads to an unequal distribution of charge, and the carbon atoms usually possess a greater negative charge than is the case with benzene. An electrophilic attack is favoured at the 2-position. Furan and thiophene are also activated towards electrophiles and react predominantly at the 2-position. In the case of indole, the substitution occurs in the pyrrole ring at 2-position and not in the benzene ring because the former involves the loss of resonance energy. Pyrrole gives tetrabromopyrrole and tetraiodopyrrole with bromine and iodine, respectively, and with chlorine gives a pentachloro derivative.

In pyridine, the electrophilic attack is preferred at the 3-position. Pyridine is less reactive than benzene and resembles nitrobenzene in its reactivity. Pyridine-N-oxide undergoes nitration with mixed nitric and sulphuric acids at 100°C to give mainly the 4-nitroderivative.

Quinoline and isoquinoline are also deactivated and reaction normally occurs in the homocyclic ring at the 5-and 8-positions. Nitration of quinoline yields almost equal amounts of 5- and 8-isomers, but isoquinoline gives entirely 5-nitroderivative.


The relative ability of substituents in an aromatic ring to donate or withdraw electrons is indicated qualitatively by Hammett substituent constants. It was observed that a plot of the logarithms of the rate constants for the alkaline hydrolysis of esters of benzoic acid against the pKa values of the corresponding acids, XC6H4CO2H, was linear; that is,

Where ρ (rho) and C are constants.

The line

describes the point for the unsubstituted compounds (X = H).

Subtraction of equation (8.2) from equation (8.1) gives:

Logk and pKa are related to free energies of activation and ionization respectively and, hence, a linear, free-energy relationship exists between the rates of ester hydrolysis and acid strengths.

Similar correlations between rate and equilibrium constants exist for various other side-chain reactions of benzene derivatives. The magnitude of ρ, which is called the reaction constant, is the slope of the line and varies with the reaction. The sign of ρ can be positive or negative according to whether the reaction rate is increased or decreased by the withdrawal of electrons.

The term (pKao − pKa is given the symbol σ (sigma) and is constant for given substituents. Equation 8.3 thus simplifies to:


log k/ko = ρσ

This is the Hammett equation.

The data for the ionization of benzoic acid and its derivatives in water at 25°C are extensive and accurate, and this was chosen as the standard reaction to which all other reactions would be compared. The value of ρ for the standard reaction is 1.00.

The Hammett substituent constant, σ, is a measure of the electron-donating or electron-withdrawing power of the particular substituent, with H being given a value of 0.00. These linear free-energy correlations only apply to meta and para substituents in aromatic systems, since ortho substituents exert steric effects, which can alter the normal electronic behaviour. It can be seen that the more negative the value, the higher the electron-donating capacity of the group; substituents with a positive σ value are electron-withdrawing.

The ρ values reflect the interaction of the substituents with the reaction centre. The methoxy group can exert only its −I effect in the meta position; the stronger +M effect dominates in the para position. Consequently, σmeta and σpara have opposite signs for this group, indicating its electron-withdrawing and electron-donating ability, respectively.


Nucleophilic substitution is not a typical reaction of aromatic compounds. However, appropriately substituted aromatic compounds do undergo nucleophilic substitution. There are two distinct and major mechanisms by which a nucleophile can be introduced into the aromatic ring. In one, the nucleophile attacks at a ring carbon atom and this type is covered in detail below. The second method depends on an electron-rich species behaving as a base and attacking at hydrogen.

8.11.1 By Addition-Elimination Mechanism (SNAr)

Whereas electrophilic attack of benzene is both well known and important, the corresponding reaction with nucleophiles is very difficult and is not typical of aromatic compounds. However, if the aromatic ring is π-electron–deficient, because an electron-withdrawing group (EWG) is present, then nucleophilic attack may occur. The mechanism for the addition-elimination sequence for nucleophilic substitution is shown below.

The initial attack disrupts the π-cloud and the resulting intermediate species, a carbanion, is stabilized by resonance. There is a close similarity between this mechanism and that proposed earlier in this chapter for electrophilic attack on benzene, although in that reaction the intermediate was a carbocation. In both cases, this first step is usually the slower and, therefore, rate-determining.

Evidence to support this mechanism for nucleophilic substitution includes isolation of several examples of the intermediate species and their structural determination by both NMR spectroscopy and X-ray crystallography. The intermediate species are called Meisenheimer complexes, many of which are strongly coloured (The first such intermediate was isolated by Meisenheimer in 1902 from the reaction of 2-ethoxy-1,3,5-trinitrobenzene with sodium methoxide).

In the second step, aromaticity is restored through elimination of an ionic species and it is here that the two reaction types diverge:

  • In electrophilic attack, a proton, H+, is lost through abstraction by a base.
  • In nucleophilic substitution the leaving group is X.

The nature of X is of fundamental importance to the success of the reaction. Displacement of hydrogen is very difficult, because the hydride ion, H, is a very poor leaving group. Benzene itself does not react with nucleophiles. The important nucleophilic substitution reactions involve the displacement of a group other than hydride ion. The more effective leaving groups are the halogens, the diazonium group and the sulphonic acid group. The diazonium group is the most effective because a very stable nitrogen molecule results from the elimination step. In these reactions, nucleophilic attack occurs at the carbon atom to which the substituent is attached. In the product, the nucleophile occupies the position of the original substituent. This process is called aromatic nucleophilic ipso attack.

Aryl halides only undergo substitution with extreme difficulty unless activated by electron-withdrawing groups, its role being to stabilize the intermediate species and so lower the energy of activation of the first step. In this respect, they serve the same purpose as donor groups in electrophilic substitution reactions. Nitro, nitrile and carbonyl are typical activating groups. Activation is best achieved when the group is ortho or para to the halogen, since both inductive and mesomeric withdrawal of electrons operate. The latter is of prime importance, providing additional resonance stabilization of the negative charge of the intermediate. This is illustrated for 1-chloro-2-nitrobenzene. A 3-substituent is much less efficient at promoting nucleophilic attack since only the −I effect assists the process. Note that an electron-withdrawing substituent also reduces the electron density of the ring, thereby helping the initial attack by the nucleophile.

8.11.2 By Elimination-Addition Mechanism

When simple aryl halides react with strong bases such as the amide ion, NH2, the base abstracts a hydrogen atom adjacent to the C-halogen unit. The resulting carbanion acts as a nucleophile and displaces the halide ion in an intramolecular process (an intramolecular reaction is one that occurs between two functional groups in the same molecule. In an intermolecular reaction, different molecules are involved). The initial product is a highly reactive species called an aryne. It is rapidly attacked by NH2, or its protonated derivative NH3, now acting as a nucleophile. The final product, which results from protonation of a second carbanion, is the new substituted benzene derivative.

One disadvantage upon the use of benzyne in synthesis is that the nucleophile may attack at either end of the triple bond of the benzyne, giving a mixture of two products if the benzyne is monosubstituted. For example, p-chlorotoluene with hydroxide ion at 340°C gives an approximately equimolar mixture of m- and p-cresol.

In the absence of nucleophiles, benzyne dimerizes to give biphenylene and, in the presence of dienes, it reacts as a dienophile to give Diels-Alder adducts.

The common feature possessed by a base, B: or B:, and a nucleophile, Nu: or Nu:, is a lone pair of electrons. They differ in that the base donates the lone pair to an H atom, whereas donation to a carbon atom is an example of nucleophilic attack. Many species with a lone pair of electrons can act as both a base and a nucleophile.


Nucleophilic attack can also occur at a position already occupied by a substituent, the ipso position. Such ipso substitutions are not common, but they are industrially useful. An example is ipso nitration by displacement of a sulphonic acid group. A proton can also displace the sulphonic acid group, with benzenesulphonic acid being converted into benzene. Nucleophilic ipso substitution reactions also occur.

The more deactivating (electron-withdrawing) the substituent, the more it increases the acidity of a COOH, OH, or NH3+ group attached to a benzene ring. For example, the pKa of substituted phenols are given below:


Attention is drawn to the lower reactivity of an unsaturated carbon atom towards nucleophilic substitution; in particular, to nucleophilic attack on an aromatic carbon atom (one in a benzene ring) that carries a potential leaving group-the SN2 {aromatic} pathway, and to how this differs from the SN2 pathway for attack at a saturated carbon atom. Finally, mention is made of the alternative pathway for attack at an aromatic carbon atom, where the attacking nucleophile is also a very strong base, which involves aryne intermediates. Substitution at a saturated carbon atom by electrophiles—electron-deficient reagents—is not a reaction of great significance, but electrophilic substitution at an unsaturated carbon atom is; particularly when the unsaturated carbon atom is part of a benzene ring-aromatic substitution.

The example of aromatic substitution that has been most studied is nitration. Consideration has been given to the nature of the attacking electrophile in nitration, to the rate equation for the reaction, to the different reaction pathways that are compatible with such an equation and to see how we can decide between them. Finally, an explanation has been given of why electrophilic attack on aromatic systems leads to overall substitution, rather than to the overall addition that might perhaps have been expected.

Attack on aromatic systems by other electrophiles—halogenation, Friedel-Crafts alkylation and acylation and sulphonation—are also described. These are, in general, found to follow reaction pathways essentially analogous to that for nitration, the point at issue commonly being the actual nature of the electrophile involved in the reaction.

Consideration is then given to electrophilic substitution on a benzene ring that already contains a substituent, that is, C6H5Y; and to how the substituent, Y, influences both the position of attack on C6H5Y (o-, m-, or p-), and the rate of attack on it, compared with the rate of similar attack on C6H6. An explanation of both influences is provided in terms of the selective stabilization of the relevant cationic intermediates involved. Reference is also made to electrophilic attack on C6H5Y in which the original substituent, Y, rather than H is replaced-ipso substitution. Some of the important key points are as follows:

  1. Electrophilic attack on benzene and related molecules proceeds by an addition-elimination mechanism. Initial attack generates a carbocationic intermediate from which the loss of a proton restores the aromatic system. The carbocation intermediate is stabilized by resonance.
  2. The rate and regiochemistry of electrophilic attack are determined by electron density in the π-system of the aromatic ring and resonance stabilization of the intermediate arenium ion.
  3. Electron-releasing substituents stabilize the positively charged intermediate and facilitate attack by an electrophile, which is directed to the ortho and para positions.
  4. Electron-withdrawing substituents deactivate the ring to further electrophilic attack and direct the new substituents to the meta position.
  5. Halogenated aromatic compound combine σ-electron withdrawal with π-electron donation, leading to slower electrophilic substitution in fused aromatic rings.
  6. Substituents introduced onto an aromatic ring retain their characteristic reactivity. For example, alkyl side chains can be oxidized, reduced, halogenated, and so forth.
  7. Nucleophilic attack on benzene does not occur. Aromatic compounds possessing a good leaving group and containing strongly electron-withdrawing groups undergo nucleophilic substitution by an addition-elimination mechanism.
  8. Arynes are generated from aryl halides by reaction with strong bases. The final outcome of the reaction is substitution of the halide.
  1. (a) Write the products of mononitration of each of the following:
    1. styrene
    2. m-cresol
    3. o-chlorophenol
    4. m-cyanophenol
    5. p-nitroacetanilide

    (b) Show why nitration of naphthalene goes exclusively at the α-position.

  2. Fill in the missing structures in the following reactions.
  3. Suggest synthesis for each of the following compounds from the starting material indicated:
    1. 3-bromoaniline from benzene
    2. 3-nitrobenzoic acid from toluene
    3. 4-nitrobenzoic acid from toluene
    4. 4-methylbenzophenone from benzoic acid
    5. 1-methoxy-2,4-dinitrobenzene from chlorobenzene
    6. 1-methoxy-3-nitrobenzene from benzenesulphonic acid
    7. 2-bromo-4-methylphenol from toluene.
  4. Formulate reasonable mechanisms for each of the following reactions.
  5. A phenyl group has an electron-withdrawing inductive effect. However, each ring of the biphenyl is more reactive than benzene toward electrophilic substitution, and the chief products are ortho- and para-isomers. Show how reactivity and orientation can be accounted for on the basis of resonance.
  6. Explain the following observations:
    1. treatment of 4–chlorotoluene with NaNH2 in liquid ammonia gives two products.
    2. reaction of benzene with 1–chloro–2–methylpropane and AlCl3 gives tert–butylbenzene.
    3. 3–chlorobutoxy benzene is heated with AlCl3.
    4. sulphonic acid group deactivates an aromatic ring to electrophilic substitution, which is directed to the 3-position.
    5. ethylbenzene is attacked preferentially at the α-position by chlorine in the presence of light.
    6. treatment of benzene sulphonic acid with hydroxide ion.
    7. 2,4,6-trinitrophenol reacts with aqueous sodium hydrogen carbonate solution but phenol does not.
    8. acetyl chloride reacts almost explosively with cold water, whereas benzoyl chloride reacts only slowly, even with dilute sodium hydroxide.
  7. The compound proparacaine is made by the following sequence of reactions. Deduce a structure for each product and draw the mechanism for each step.
  8. Nitroso group (N=O) activates ortho- and para-positions toward both nucleophilic and electrophilic aromatic substitution; the group apparently can either withdraw or release electrons upon demand by the attacking reagent. Show how this might be accounted for.
  9. Draw suitable mechanism for the following reactions.
  10. (a) Write an equation for the generation of NO2+ from nitric acid alone and from nitric acid in the presence of H2SO4.

    (b) Write an equation for the formation from H2SO4 of each of the following sulphonating electrophiles:

    1. H3SO4+
    2. HSO3+
    3. H2S2O7
    4. SO3.

    (c) For each of the following compounds, indicate which ring you would expect to be attacked in nitration, and give structures of the principal products.

  11. Outline all steps involved in the synthesis of following compounds from benzene and / or toluene using any needed reagents.
    1. p-bromonitrobenzene
    2. p-dichlorobenzene
    3. m-bromobenzenesulphonic acid
    4. p-bromobenzoic acid
    5. o-nitro-m-bromobenzoic acid
    6. 1,3,5-trinitrobenzene
    7. 3,5-dinitrobenzoic acid
    8. p-methyl-o-nitrophenol
    9. 2,4,6-tribromoaniline.
  1. Which of the following reactions is classed as a nucleophilic aromatic substitution?
    1. Sulphonation of benzene
    2. Reaction of a proton with dinitrofluorobenzene
    3. Reaction of the diazonium cation with phenol
    4. The conversion of pyridine to pyrrolidine
    5. The hydrolysis of benzyl bromide
  2. Electrophilic substitution in aromatic compounds may proceed via sigma-complex formation. Indicate which one of the following statements is incorrect with regard to this mechanism.
    1. The electrophilic-attacking species may be a cation or a polarized molecule.
    2. When a cation attacks the aromatic ring it removes a pair of electrons from the sextet to form a carbanion.
    3. The sigma-complex is a highly reactive intermediate.
    4. In sigma-complex formation, the C–H bond remains intact in the rate-determining step.
    5. A sigma-complex undergoes further reaction to stabilize itself.
  3. Which one of the following groups X in the compound is m-directing in electrophilic substitution reactions?

    1. −OCH3
    2. −NH.CO.CH3
    3. −CO.CH3
    4. −N(CH3)2
  4. The principal reactions of aromatic compounds are:
    1. nucleophilic substitution
    2. nucleophilic addition-with-elimination
    3. electrophilic addition-with-elimination
    4. electrophilic addition
  5. Which of the following compounds undergoes nucleophilic substitution most readily?
  6. The orientation of the products (o-, m-, p-) from aromatic substitution reactions is governed by
    1. the nature of the reaction medium.
    2. the type of substituent already present in the aromatic ring.
    3. the relative stabilities of the products.
    4. the delocalization of the pi-electron system.
  7. The relative rates of mononitration of R-C6H5, where R = −CH3, −NO2, −OH, −Cl is:
    1. CH3 > OH > NO2 > Cl
    2. OH > Cl > CH3 > NO2
    3. OH > CH3 > NO2 > Cl
    4. OH > CH3 > Cl > NO2
    5. CH3 > OH > Cl > NO2
  8. Where does the above compound substitute on electrophilic attack.

    1. meta
    2. ortho
    3. ortho and para
    4. para
  9. One of the completions a to e is incorrect. Choose the letter corresponding to the incorrect completion. In the nitration of benzene by concentrated sulphuric and concentrated nitric acid
    1. the reaction is irreversible.
    2. the rate determining step is the removal of H+ from the intermediate
    3. the attacking electrophile is NO2+
    4. the second nitro group enters the benzene ring meta to the first nitro group
    5. If the concentrated sulphuric acid is replaced by some other strong acid such as hydrofluoric acid, the reaction will still proceed at a similar rate.
  10. One of the completions a to e is incorrect. Choose the letter corresponding to the incorrect completion, Pyrrole will undergo the following reactions to give the stated products.
    1. Sulphonation with C5H5N.SO3 yields mainly pyrrole-2-sulphonic acid
    2. Benzene diazonium chloride reacts to give benzeneazo-2-pyrrole
    3. Acetic anhydride yields methyl-2-pyrryl ketone
    4. Chloroform and potassium hydroxide react to give mainly 3-chloropyridine
    5. nitration with a mixture of nitric acid and acetic anhydride yields mainly 3-nitropyrrole.
  11. Which statement is most relevant to the fact that pyridine reacts with sodamide, NaNH2, in liquid ammonia to yield 2-amino pyridine.
    1. Pyridine readily undergoes electrophilic substitution.
    2. Pyridine resists attack by electrophiles.
    3. Pyridine is soluble in liquid ammonia.
    4. The amide ion is a strong base in liquid ammonia.
    5. Pyridine is susceptible to nucleophilic attack.
  12. Where does the above compound substitute on electrophilic attack?

    1. meta
    2. ortho
    3. ortho and para
    4. para
  13. Which of the following sets of substituents, when separately attached to the aromatic ring, is most likely to ‘activate’ nucleophilic aromatic substitution?
    1. NO2, CH3, CN
    2. OH, CN, Cl
    3. NO, COCH3, +N(CH3)3
    4. COOH, Br, NH2
    5. CF3, CHO, OCH3
  14. The relative reactivities of benzene, aniline, nitrobenzene and toluene are:
    1. benzene > toluene > aniline > nitrobenzene
    2. nitrobenzene > aniline > toluene > benzene
    3. toluene > aniline > nitrobenzene > benzene
    4. aniline > toluene > benzene > nitrobenzene
  15. A compound A (C8H7ClO2) was hydrolyzed with dilute aqueous sodium hydroxide to give, after acidification, a compound B (C8H8O3). Oxidation of compound B with acidic sodium dichromate gave C8H6O4 which, when heated alone, gave C8H4O3. What is the most likely structure for A?
  16. Which of the following groups has an electron-withdrawing mesomeric effect?
    1. −CH2.CH3
    2. −Cl
    3. −OCH3
    4. −CN
    5. −NH.CH3
  17. A compound was found to be insoluble in dilute aqueous sodium hydroxide solution. A solution of the compound in dry benzene gave a colourless gas on the adddition of sodium metal. On shaking with alcoholic silver nitrate solution, a pale yellow precipitate was formed. Which of the following compounds would satisfy these observations?
  18. The reaction of toluene with chlorine in the presence of light gives: