Media Portfolio

Chapter 17
Reactions of Aromatic Compounds

17-00-01UN

Title	Electrophilic Aromatic Substitution
Caption	Although benzene's pi electrons are in a stable aromatic system, they are available to attack a strong electrophile to give a carbocation. This resonance stabilized carbocation is called a sigma complex because the electrophile is joined to the benzene ring by a new sigma bond.
Notes	The reaction is endothermic because benzene loses aromaticity when it attacks an electrophile. Aromaticity is regained by loss of a proton. The overall reaction is called an electrophilic aromatic substitution.
Keywords	electrophilic aromatic substitution, sigma complex, aromaticity

17-01

Labeled

Title	Mechanism of Electrophilic Aromatic Substitution
Caption	The overall reaction is the substitutionof an electrophile (E+) for a proton (H+) on the aromatic ring: electrophilic aromatic substitution.
Notes	The first step of the mechanism is the attack on the electrophile to form the sigma complex. The formation of the complex is followed by the loss of a proton to give the substitution product.
Keywords	electrophilic aromatic substitution, aromaticity, sigma complex

17-01-01UN

Labeled

Title	Mechanism of Benzene Bromination
Caption	Bromination follows the general mechanism for electrophilic aromatic substitution. Bromine itself is not sufficiently electrophilic to react with benzene, but a strong Lewis acid such as FeBr3 catalyzes the reaction.
Notes	The first step of the mechanism is the formation of a stronger electrophile. The catalyst reacts with the Br2 to form a strong electrophile. The attack of the benzene on the electrophile and the loss of a proton gives bromobenzene as the main product.
Keywords	Lewis acid, electrophile, catalyst

17-02

Labeled

Title	Energy Diagram for the Bromination of Benzene
Caption	Figure 17-1 The energy diagram for the bromination of benzene shows that the first step is endothermic and rate limiting, and the second step is strongly exothermic.
Notes	The overall reaction is exothermic, but the attack of the electrophile is the rate limiting step because the ring loses its aromaticity.
Keywords	endothermic, exothermic, rate-limiting

17-02-04UN

Labeled

Title	Mechanism for the Nitration of Benzene
Caption	The mechanism is similar to other sulfuric acid catalyzed dehydrations. Sulfuric acid protonates the hydroxyl group of nitric acid, allowing it to leave as water, forming a nitronium ion.
Notes	Nitric acid is not the electrophile, it is a nitronium ion formed by protonation and dehydration of HNO3 by H2SO4. It is the nitronium ion the species attacked by the benzene. Loss of a proton from the sigma complex produces nitrobenzene.
Keywords	nitronium ion

17-02-08UN

Labeled

Title	Desulfonation Reaction
Caption	Sulfonation is reversible, and a sulfonic acid group may be removed from an aromatic ring by heating in dilute sulfuric acid.
Notes	In the desulfonation reaction a proton adds to the ring (the electrophile) and loss of sulfur trioxide gives back benzene.
Keywords	desulfonation, sulfonation

17-02-12UN

Labeled

Title	Nitration of Toluene
Caption	Toluene reacts about 25 times faster than benzene under the same conditions. We say that toluene is activated toward electrophilic aromatic substitutions and that the methyl group is an activating group.
Notes	Nitration of toluene gives three products; o-nitrotoluene (60%), m-nitrotoluene (4%), and p-nitrotoluene (36%).
Keywords	nitration, toluene, activated, activation, activating group

17-02-15UN

Labeled

Title	Ortho-, Para- and Meta- Attack on Toluene
Caption	In ortho or para substitution of toluene, the positive charge is spread over two secondary carbons and one tertiary carbon (bearing the CH3 group). The sigma complex for the meta substitution has its positive charge spread over secondary carbons.
Notes	Ortho and para attacks are preferred because their resonance structures include one tertiary carbocation, while all the resonance structures for the meta attack have secondary carbocations only.
Keywords	ortho, para, meta

17-03

Labeled

Title	Energy Diagram for the Nitration of Benzene and Toluene
Caption	Figure 17-2 The methyl group of the toluene stabilizes the sigma complexes and the transition states leading to them. This stabilization is most effective when the methyl group is ortho or para to the site of substitution.
Notes	Stabilized carbocations have lower energy than unstabilized ones, so the ortho and para attack of toluene is lower in energy than the meat attack. The sigma complex for the nitration of benzene is higher in energy than for toluene.
Keywords	ortho, meta, para, sigma complex, intermediate, carbocation, stabilized

17-03-04UN

Labeled

Title	Electrophilic Aromatic Substitution of Methoxybenzene
Caption	Resonance shows that the methoxy group effectively stabilizes the sigma complex if it is ortho or para to the site of substitution, but not if it is meta. Resonance stabilization is provided by a pi bond between the -OCH3 substitution of the ring.
Notes	The nonbonding pair of electrons on the heteroatom can further delocalize the positive charge of the carbocation, making the ortho and para substitutions specially stable.
Keywords	methoxy group, sigma complex, stabilized carbocation

17-03-08UN

Labeled

Title	Bromination of Aniline
Caption	Like an alkoxy group, a nitrogen atom with a nonbonding pair of electrons serves as a powerful activating group. For example, aniline undergoes a fast bromination (without a catalyst) in bromine water to give the tribromide. Nitrogen's nonbonding electrons provide resonance stabiliation to the sigma complex if attack takes place ortho or para to the position of the nitrogen atom.
Notes	The more activated the ring, the easier it can undergo electrophilic aromatic substitutions. However, polysubstitutions will also increase with activation.
Keywords	alkoxy, aniline, activated ring

17-03-09Summ

Labeled

Title	Activating Ortho, Para Directors
Caption	Any substituent with a lone pair of electrons on the atom bonded to the ring can provide resonance stabilization to a sigma complex.
Notes	Activating substituents are those that can provide a lone pair of electrons to stabilize the carbocation in the ring. Electrophilic substitutions with these type of substituent tend to occur ortho and para so they are referred to as ortho/para directors.
Keywords	ortho/para director, resonance stabilization

17-03-10UN

Labeled

Title	Meta Directing Substituents
Caption	Nitrobenzene is about 100,000 times less reactive than benzene toward electrophilic aromatic substitution. For example, nitration of nitrobenzene requires concentrated nitric and sulfuric acids at temperatures above 100oC. Nitration proceeds slowly, giving the meta isomer as the major product.
Notes	Electron withdrawing groups deactivate the ring and direct any incoming group toward the meta position.
Keywords	meta director, deactivator

17-03-13UN

Labeled

Title	Ortho, Meta, and Para Attack on Nitrobenzene
Caption	In ortho and para substitution, one of the carbon atoms bearing the positive charge is the carbon attached to the positively charged nitrogen atom of the nitro group. Since like charges repel, this close proximity of the two positive charges is especially unstable.
Notes	The meta resonance structures do not have the two positive charges together so it is a more stable sigma complex.
Keywords	meta director, sigma complex

17-04

Labeled

Title	Energy Diagram for the Substituion of Nitrobenzene
Caption	Figure 17-3 Nitrobenzen is deactivated toward electrophilic aromatic substitution at any position, but deactivation is strongest at the ortho and para positions. Reaction occurs at the meta position, but it is slower than the reaction of benzene.
Notes	The nitro group deactivates the ring toward substitution so the reactions take longer even under strong conditions.
Keywords	deactivation

17-04-02Summ

Labeled

Title	Summary of Deactivating Meta DIrectors
Caption	The following summary table lists some common substituents that are deactivating and meta-directing. Resonance forms are also given to show how a positive charge arises on the atom bonded to the aromatic ring.
Notes
Keywords	deactivation, meta directors, resonance

17-05

Labeled

Title	Energy Diagram for Electrophilic Substitutions on Chlorobenzene
Caption	Higher energies are required for the reactions of chlorobenzene, especially for attack at the meat position.
Notes	Although halogens are deactivating groups, a look at the energy diagram of chlorobenzene shows that they are ortho/para directors. Halogen's electronegativity will deactivate the ring, but the non-bonding pairs of electrons will stabilize the carbocations produced during ortho and para attacks.
Keywords	halogen, deactivation, meta director, ortho director, para director

17-05-01Summ

Labeled

Title	Summary of Directing Effects of Substituents
Caption	Activators are ortho. para-directing, and deactivators are meta-directing
Notes	The most activating groups are those with non-bonding electrons such as -OH, -NH2, and -OR. Deactivators are electronwithdrawing groups that have a partial positive or a positively charged atom directly attached to the ring. Halogens are the exception because eventhough they deactivate the ring, they are ortho, para-directors.
Keywords	ortho-director, para-director, meta-director, activating, deactivating

17-05-03UN

Labeled

Title	Effects of Multiple Substituents on Electrophilic Aromatic Substitution
Caption	Two or more substituents exert a combined effect on the reactivity of an aromatic ring. If the groups reinforce each other, the result is easy to predict. When directing effects of two or more substituents conflict, it is more difficult to predict where an electrophile will react.
Notes	In the case of m-xylene, both methyl groups are ortho, para-directos so they will both directs the incoming groups to the same carbons. Sterically hindered positions will not react. In the case of p-nitrotoluene the methyl will direct ortho while the nitro will direct meta. In this compounds both groups direct to the same positions, so only one product will be obtained.
Keywords	ortho-director, meta-director, acitvator, deactivator

17-05-04UN

Labeled

Title	Conflicting Effects of Substituents
Caption	When the directing effects of two or more substituents conflict, it is more difficult to predict where an electrophile will react. In many cases, mixtures result. When there is a conflict between an activating and a deactivating group, the activating group usually directs the substitution.
Notes	In the nitration of o-xylene, the methyl groups direct to different ortho, para positions. There are two different positions in the compound that the electrophile can react with. A mixture of substitutions on both sites will be obtained.
Keywords	ortho-director, meta-director, acitvator, deactivator, o-xylene

17-05-16UN

Labeled

Title	Friedel-Crafts Alkylation
Caption	Carbocations are perhaps the most important electrophiles capable of substituting onto aromatic rings, because this substitution forms a new carbon-carbon bond.
Notes	The addition of alkyl groups to a benzene ring is called the Friedel-Craft alkylation. A lewis acid is used as a catalyst to generate the carbocation from the alkyl halide (2o or 3o) or to activate the alkyl halide (1o or methyl halide) toward nucleophilic attack.
Keywords	Friedel-Crafts alkylation, alkyl halide, catalyst

17-05-18UN

Labeled

Title	Mechanism of Friedel-Crafts Alkylation
Caption	Friedel-Crafts alkylations are used with a wide variety of primary, secondary, and tertiary alkyl halides. With secondary and tertiary halides, the reacting electrophile is probably the carbocation.
Notes	The aluminum trichloride reacts with the alkyl halide to form a stable tertiary carbocation. The cation reacts with the benzene and, after losing a proton, will give t-butylbenzene is yields of about 90%.
Keywords	aluminum trichloride, carbocation

17-05-20UN

Labeled

Title	Mechanism of Friedel-Crafts Alkylation with Primary Alkyl Halides
Caption	With primary alkyl halides, the free primary carbocation is too unstable. The actual electrophile is a complex of aluminum chloride with alkyl halide. In this complex, the carbon-halogen bond is weakened as there is a considerable positive charge on the carbon atom.
Notes	The benzene ring attacks the activated carbon of the alkyl halide, displacing a molecule of aluminum tetrachloride. One of the chlorides on the catalyst will abstract a proton from the sigma complex forming HCl and restoring aromaticity.
Keywords	sigma complex, aluminum chloride

17-05-21UN

Labeled

Title	Protonation of Alkenes for Friedel-Crafts Alkylation
Caption	Alkenes are protonated by HF to give carbocations. Fluoride ion is a weak nucleophile and does not immediately attack the carbocation. If benzene is present, electrophilic substitution occurs.
Notes	The protonation of an alkene follows the Markovnikov rule, so from propene a t-butyl cation will be formed and added to the ring.
Keywords	HF, fluoride ion

17-05-22UN

Labeled

Title	Treatment of Alcohols with BF3 for Friedel-Crafts Alkylation
Caption	Alcohols commonly form carbocations when treated with Lewis acids such as boron trifluoride (BF3). If benzene (or an activated benzene derivative) is present, substitutions may occur.
Notes	The BF3 reacts with the oxygen of the alcohol forming a carbocation. Benzene will attack the carbocation and after proton loss produce the alkylated benzene. One full equivalent of BF3 is needed for the reaction.
Keywords	boron trifluoride (BF3)

17-05-25UN

Labeled

Title	Carbocation Rearrangements During Friedel-Crafts Alkylation
Caption	The Friedel-Crafts alkylation is succeptible to carbocation rearrangements. As a result, only certain alkylbenzenes can be made using the Friedel-Crafts alkylation.
Notes	Reaction that have carbocation intermediates suffer from possible carbocation rearrangements to form more stable carbocations.
Keywords	carbocation rearrangements

17-05-29UN

Labeled

Title	Friedel-Crafts Acylation
Caption	In the presence of aluminum chloride, an acyl chloride reacts with benzene (or an activated benzene derivative) to give a phenyl ketone; an acylbenzene.
Notes	This reaction is analogous to the alkylation but the product is a phenyl ketone.
Keywords	acyl chloride, acylbenzene, acitvated benzene

17-05-30UN

Labeled

Title	Mechanism of Friedel-Crafts Acylation
Caption	The mechanism of the Friedel-Crafts acylation resembles that of the alkylation, except that the carbonyl group helps stabilize the cationic intermediate.
Notes	The first step of the reaction is the formation if an acylium ion (the electrophilic species) by reaction of the acyl chloride with the catalyst. The benzene attacks the acylium ion and after proton loss and aqueous hydrolysis, the acylbenzene is obtained.
Keywords	acylium ion, acyl chloride, acylbenzene

17-05-35UN

Labeled

Title	Clemmensen Reduction
Caption	How do we synthesize alkylbenzenes that cannot be made by Friedel-Crafts alkylation? We use the Friedel-Crafts acylation, then we reduce the acylbenzene to the alkylbenzene using the Clemmensen reduction; treatment with aqueous HCl and amalgamated zinc.
Notes	Acylation and reduction with the Clemmensen reaction is a sequence used to put alkyl groups on rings that would rearrange and polyalkylate with the Friedel-Craft alkylation .
Keywords	Clemmensen reduction, acylation, zinc amalgam

17-05-43UN

Labeled

Title	Mechanism of Nucleophilic Aromatic Substitution (Addition-Elimination)
Caption	Consider the reaction os 2,4-dinitrochlorobenzene with sodium hydroxide. When hydroxide (the nucleophile) attacks the carbon bearing the chlorine, a negatively charged sigma complex results. The negative charge is delocalized over the ortho and para carbons of the ring and further delocalized over the electron-withdrawing nitro groups.
Notes	Without the nitro groups ortho and para to the chlorine the reaction would not occur.
Keywords	nucleophilic aromatic substitution, sigma complex, addition-elimination

17-05-44UN

Labeled

Title	Activated Position in Nucleophilic Aromatic Substitution
Caption	Nitro groups ortho and para to the halogen stabilize the intermediate (and the transition state leading to it). Without electron withdrawing groups in these positions, formation of the negatively charged sigma complex is unlikely.
Notes	Eventhough fluoride is a bad leaving group in SN1 and SN2 mechanisms it will undergo nucleophilic aromatic substitution.
Keywords	nucleophilic aromatic substitution, sigma complex, addition-elimination

17-05-48UN

Labeled

Title	Benzyne Mechanism for Nucleophilic Aromatic Substitution
Caption	Sodium amide reacts as a base, abstracting the proton. The product is a carbanion with a negative charge and a nonbonding pair of electrons localized in the sp2 orbital that once formed the C-H bond. The carbanion expells the bromide to become a neutral species.
Notes	The benzyne intermediate forms when the bromide is expelled and the electrons on the sp2 orbital adjacent to it overlap with the empty sp2 orbital of the carbon that lost the bromide. Benzynes are very reactive species due to the high strain of the triple bond.
Keywords	Benzyne, carbanion, nucleophilic aromatic substitution

17-05-49UN

Labeled

Title	Nucleophilic Substitution on the Benzyne Intermediate
Caption	Amide ion is a strong nucleophile, attacking at either end of the weak, reactive benzyne triple bond. Subsequent protonation gives toluidine. About half the product results from attack by the amide ion at the meta carbon, and about half from attack at the para carbon.
Notes	When the substrate do not have strong withdrawing groups, the reaction will have bezynes as intermediates.
Keywords	Benzyne, nucleophilic aromatic substitution

17-05-50UN

Labeled

Title	Mechanisms for Nucleophilic Aromatic Substitution
Caption	The benzyne mechanism operates when the halobenzene is unactivated toward nucleophilic aromatic substitution, and forcing conditions are used with a strong base.
Notes	When the ring is activated toward nucleophilic aromatic substitution with strong withdrawing groups the normal addition-elimination mechanism will take place.
Keywords	Benzyne, carbanion, nucleophilic aromatic substitution, addition-elimination

17-06

Labeled

Title	Mechanism of the Birch Reduction
Caption	A solution of sodium in liquid ammonia contains solvated electrons that can add to benzene, forming a radical anion. The strongly basic radical anion abstract a proton from the alcohol in the solvent, giving a cyclohexadienyl radical. The radical quickly adds another solvated electron to from a cyclohexadienyl anion. Protonation of this anion gives the reduced product.
Notes	The product of the Birch reduction of benzene is 1,4-cyclohexadiene.
Keywords	Birch reduction, cyclohexadienyl radical, cyclohexadienyl anion, 1,4-cyclohexadiene, solvent

17-06-04UN

Labeled

Title	Side Chain Oxidation of Alkyl Chains
Caption	An aromatic ring imparts extra stability to the nearest carbon atom of its side chains. The aromatic ring and one carbon atom of a side chain can survive a vigorous permanganate oxidation. The product is a carboxylate salt of benzoic acid.
Notes	Besides KMnO4, hot chromic acid can also be used with similar results.
Keywords	side chain, oxidation, potassium permanganate, carboxylate salt, benzoic acid,

17-06-06UN

Labeled

Title	Side Chain Halogenation
Caption	Alkylbenzenes undergo free-radical halogenation much more easily than alkanes because abstraction of a hydrogen atom at a benzylic position gives a resonance-stabilized benzylic radical.
Notes	Chlorination can give mixtures of products, but bromination will only react at the benzylic position. NBS can be used for this reaction.
Keywords	alkylbenzene, free-radical halogenation, chlorination, bromination, NBS, benzylic position

17-06-10UN

Labeled

Title	Nucleophilic Substitution at the Benzylic Position
Caption	Benzylic halides are more reactive than alkyl halides in SN1 and SN2 substitution reactions. Because they form relatively stable carbocations, benzyl halides undergo SN1 reactions relatively easily.
Notes	Benzylic carbocations are more stable because the positive charge can be delocalized on three carbons in the ring.
Keywords	benzylic halides, carbocations, SN1 substitution, SN2 substitution

17-07

Labeled

Title	Transition State for the SN2 Displacement of a Benzylic Halide
Caption	Figure 17-5 The transition state for SN2 displacement of a benzylic halide is stabilized by conjugation with the pi electrons in the ring.
Notes	The empty, unhybridized p orbital of the carbocation can overlap with the p orbitals on the carbons of the ring, stabilizing the positive charge.
Keywords	transition state, benzylic halide, SN2 substitution

Chapter 17Reactions of Aromatic Compounds

Chapter 17
Reactions of Aromatic Compounds