Chemistry 243 - Lecture 13 1

C 2004 Barry Linkletter, UPEI

Lecture 13

Chemistry of Aromatic Compounds

Chapter 5

Chemistry 243 - Lecture 13 2

C 2004 Barry Linkletter, UPEI

Substitution Reactions of Benzene and

Its Derivatives

� Benzene is aromatic: a cyclic conjugatedcompound with 6 ! electrons

� Reactions of benzene lead to the retention ofthe aromatic core

� Electrophilic aromatic substitution replaces aproton on benzene with another electrophile

Chemistry 243 - Lecture 13 3

C 2004 Barry Linkletter, UPEI

Bromination of Aromatic Rings

� Benzene�s ! electrons participate as a Lewis basein reactions with Lewis acids

� The product is formed by loss of a proton, whichis replaced by bromine

� FeBr3 is added as a catalyst to polarize thebromine reagent

Chemistry 243 - Lecture 13 4

C 2004 Barry Linkletter, UPEI

Addition Intermediate in Bromination

� The addition of bromine occurs in two steps

� In the first step the ! electrons act as anucleophile toward Br2 (in a complex with FeBr3)

� This forms a cationic addition intermediate frombenzene and a bromine cation

� The intermediate is not aromatic and thereforehigh in energy (see Figure 16.2)

Chemistry 243 - Lecture 13 5

C 2004 Barry Linkletter, UPEI

Formation of Product from

Intermediate

� The cationic additionintermediate transfersa proton to FeBr4

-

(from Br- and FeBr3)

� This restoresaromaticity (in contrastwith addition inalkenes)

Chemistry 243 - Lecture 13 6

C 2004 Barry Linkletter, UPEI

Other Aromatic Substitutions

� The reaction with bromine involves a mechanismthat is similar to many other reactions of benzenewith electrophiles

� The cationic intermediate was first proposed by G.W. Wheland of the University of Chicago and isoften called the Wheland intermediate

Chemistry 243 - Lecture 13 7

C 2004 Barry Linkletter, UPEI

Aromatic Chlorination and Iodination

� Chlorine and iodine (but not fluorine, which is too reactive)

can produce aromatic substitution with the addition of other

reagents to promote the reaction

� Chlorination requires FeCl3

� Iodine must be oxidized to form a more powerful I+ species

(with Cu+ or peroxide)

Chemistry 243 - Lecture 13 8

C 2004 Barry Linkletter, UPEI

Aromatic Nitration

� The combination of nitric acid and sulfuric acid producesNO2

+ (nitronium ion)

� The reaction with benzene produces nitrobenzene

Chemistry 243 - Lecture 13 9

C 2004 Barry Linkletter, UPEI

Aromatic Sulfonation

� Substitution of H by SO3 (sulfonation)

� Reaction with a mixture of sulfuric acid and SO3

� Reactive species is sulfur trioxide or its conjugate acid

� Reaction occurs via Wheland intermediate and is reversible

Chemistry 243 - Lecture 13 10

C 2004 Barry Linkletter, UPEI

Alkylation of Aromatic Rings: TheFriedel�Crafts Reaction

� Aromatic substitution ofa R+ for H

� Aluminum chloridepromotes the formationof the carbocation

� Wheland intermediateforms

Chemistry 243 - Lecture 13 11

C 2004 Barry Linkletter, UPEI

Limitations of the Friedel-Crafts

Alkylation

� Only alkyl halides can be used (F, Cl, I, Br)

� Aryl halides and vinylic halides do not react (theircarbocations are too hard to form)

� Will not work with rings containing an amino groupsubstituent or a strongly electron-withdrawing group

Chemistry 243 - Lecture 13 12

C 2004 Barry Linkletter, UPEI

Control Problems

� Multiple alkylations can occur because the first

alkylation is activating

Chemistry 243 - Lecture 13 13

C 2004 Barry Linkletter, UPEI

Carbocation Rearrangements During

Alkylation� Similar to those that occur during electrophilic additions to

alkenes

� Can involve H or alkyl shifts

Chemistry 243 - Lecture 13 14

C 2004 Barry Linkletter, UPEI

Acylation of Aromatic Rings

� Reaction of an acid chloride (RCOCl) and an aromatic ring inthe presence of AlCl3 introduces acyl group, !COR

� Benzene with acetyl chloride yields acetophenone

Chemistry 243 - Lecture 13 15

C 2004 Barry Linkletter, UPEI

Mechanism of Friedel-Crafts Acylation

� Similar to alkylation

� Reactive electrophile: resonance-stabilized acylcation

� An acyl cation does not rearrange

Chemistry 243 - Lecture 13 16

C 2004 Barry Linkletter, UPEI

Substituent Effects in Aromatic Rings

� Substituents can cause a compound to be (much) more or(much) less reactive than benzene

� Substituents affect the orientation of the reaction � thepositional relationship is controlled

� ortho- and para-directing activators, ortho- and para-directingdeactivators, and meta-directing deactivators

Chemistry 243 - Lecture 13 17

C 2004 Barry Linkletter, UPEI

Origins of Substituent Effects

� An interplay of inductive effects and resonanceeffects

� Inductive effect - withdrawal or donation of

electrons through a ! bond

� Resonance effect - withdrawal or donation of

electrons through a " bond due to the overlap of a

p orbital on the substituent with a p orbital on the

aromatic ring

Chemistry 243 - Lecture 13 18

C 2004 Barry Linkletter, UPEI

Inductive Effects

� Controlled by electronegativity and the polarity of

bonds in functional groups

� Halogens, C=O, CN, and NO2 withdraw electrons

through ! bond connected to ring

� Alkyl groups donate electrons

Chemistry 243 - Lecture 13 19

C 2004 Barry Linkletter, UPEI

Resonance Effects � Electron

Withdrawal

� C=O, CN, NO2 substituents withdraw electrons

from the aromatic ring by resonance

� ! electrons flow from the rings to the

substituents

Chemistry 243 - Lecture 13 20

C 2004 Barry Linkletter, UPEI

Resonance Effects � Electron Donation

� Halogen, OH, alkoxyl (OR), and amino substituentsdonate electrons

� ! electrons flow from the substituents to the ring

� Effect is greatest at ortho and para

Chemistry 243 - Lecture 13 21

C 2004 Barry Linkletter, UPEI

Contrasting Effects

� Halogen, OH, OR, withdraw electrons inductively

so that they deactivate the ring

� Resonance interactions are generally weaker,

affecting orientation

� The strongest effects dominate

Chemistry 243 - Lecture 13 22

C 2004 Barry Linkletter, UPEI

An Explanation of Substituent Effects

� Activating groupsdonate electrons tothe ring, stabilizingthe Whelandintermediate(carbocation)

� Deactivating groupswithdraw electronsfrom the ring,destabilizing theWhelandintermediate

Chemistry 243 - Lecture 13 23

C 2004 Barry Linkletter, UPEI

Ortho- and Para-Directing Activators:

Alkyl Groups

� Alkyl groups activate: direct further substitution topositions ortho and para to themselves

� Alkyl group is most effective in the ortho and para positions

Chemistry 243 - Lecture 13 24

C 2004 Barry Linkletter, UPEI

Ortho- and Para-Directing Activators:

OH and NH2

� Alkoxyl, and amino groups have a strong, electron-donating resonance effect

� Most pronounced at the ortho and para positions

Chemistry 243 - Lecture 13 25

C 2004 Barry Linkletter, UPEI

Ortho- and Para-Directing Deactivators:

Halogens

� Electron-withdrawing inductive effect outweighsweaker electron-donating resonance effect

� Resonance effect is only at the ortho and parapositions, stabilizing carbocation intermediate

Chemistry 243 - Lecture 13 26

C 2004 Barry Linkletter, UPEI

Meta-Directing Deactivators

� Inductive and resonance effects reinforce each other

� Ortho and para intermediates destabilized by deactivationfrom carbocation intermediate

� Resonance cannot produce stabilization

Chemistry 243 - Lecture 13 27

C 2004 Barry Linkletter, UPEI

Summary Table: Effect of Substituents inAromatic Substitution

Chemistry 243 - Lecture 13 28

C 2004 Barry Linkletter, UPEI

Trisubstituted Benzenes: Additivity of

Effects

� If the directing effects of the two groups are the

same, the result is additive

Chemistry 243 - Lecture 13 29

C 2004 Barry Linkletter, UPEI

Substituents with Opposite

Effects� If the directing effects of two groups oppose

each other, the more powerful activating group

decides the principal outcome

� Usually gives mixtures of products

Chemistry 243 - Lecture 13 30

C 2004 Barry Linkletter, UPEI

Meta-Disubstituted Compounds Are

Unreactive� The reaction site is too hindered

� To make aromatic rings with three adjacent substituents, itis best to start with an ortho-disubstituted compound

Chemistry 243 - Lecture 13 31

C 2004 Barry Linkletter, UPEI

Nucleophilic Aromatic Substitution

� Aryl halides withelectron-withdrawingsubstituents ortho andpara react withnucleophiles

� Form additionintermediate(Meisenheimer complex)that is stabilized byelectron-withdrawal

� Halide ion is lost to givearomatic ring

Chemistry 243 - Lecture 13 32

C 2004 Barry Linkletter, UPEI

Benzyne

� Phenol is prepared on an industrial scale by treatment ofchlorobenzene with dilute aqueous NaOH at 340°C underhigh pressure

� The reaction involves an elimination reaction that gives atriple bond

� The intermediate is called benzyne

Chemistry 243 - Lecture 13 33

C 2004 Barry Linkletter, UPEI

Evidence for Benzyne as an

Intermediate

� Bromobenzene with 14C only at C1 gives substitution productwith label scrambled between C1 and C2

� Reaction proceeds through a symmetrical intermediate inwhich C1 and C2 are equivalent� must be benzyne

Chemistry 243 - Lecture 13 34

C 2004 Barry Linkletter, UPEI

Structure of Benzyne

� Benzyne is a highly distorted alkyne

� The triple bond uses sp2-hybridized carbons, notthe usual sp

� The triple bond has one ! bond formed by p�poverlap and by weak sp2�sp2 overlap

Chemistry 243 - Lecture 13 35

C 2004 Barry Linkletter, UPEI

Oxidation of Aromatic Compounds

� Alkyl side chains can be oxidized to !CO2H by strong

reagents such as KMnO4 and Na2Cr2O7 if they have a C-H

next to the ring

� Converts an alkylbenzene into a benzoic acid, Ar!R "

Ar!CO2H

Chemistry 243 - Lecture 13 36

C 2004 Barry Linkletter, UPEI

Bromination of Alkylbenzene Side

Chains

� Reaction of an alkylbenzene with N-bromo-succinimide (NBS) and benzoyl peroxide (radicalinitiator) introduces Br into the side chain

Chemistry 243 - Lecture 13 37

C 2004 Barry Linkletter, UPEI

Mechanism of NBS (Radical) Reaction

� Abstraction of a benzylic hydrogen atom generates anintermediate benzylic radical

� Reacts with Br2 to yield product

� Br· radical cycles back into reaction to carry chain

� Br2 produced from reaction of HBr with NBS

Chemistry 243 - Lecture 13 38

C 2004 Barry Linkletter, UPEI

Reduction of Aromatic Compounds

� Aromatic rings are inert to catalytic hydrogenation underconditions that reduce alkene double bonds

� Can selectively reduce an alkene double bond in the presenceof an aromatic ring

� Reduction of an aromatic ring requires more powerfulreducing conditions (high pressure or rhodium catalysts)

Chemistry 243 - Lecture 13 39

C 2004 Barry Linkletter, UPEI

Reduction of Aryl Alkyl Ketones

� Aromatic ring activates neighboring carbonylgroup toward reduction

� Ketone is converted into an alkylbenzene bycatalytic hydrogenation over Pd catalyst

Chemistry 243 - Lecture 13 40

C 2004 Barry Linkletter, UPEI

For Next Class

� Read Chapter 6

� Stereochemistry