Chapter 5 Aromatic Compounds Suggested Problems: 22,24,26b-f,27,32-35,37-8,41-2,47-8,55,58

Aromatic Compounds Aromatic was once used to described some fragrant compounds in early 19th century Not correct: later they were grouped by chemical behavior (unsaturated compounds that undergo substitution rather than addition) Current: distinguished from aliphatic compounds by electronic configuration

5.1 Structure of Benzene Benzene reacts only very slowly with Br2 to give bromobenzene (where Br replaces H) This is substitution rather than the rapid addition reaction common to compounds with C=C, suggesting that, in benzene, there is a higher energy barrier to reaction

5.2 Naming Aromatic Compounds Many common names (toluene = methylbenzene; aniline = aminobenzene; phenol = hydroxybenzene) Monosubstituted benzenes have systematic names as hydrocarbons with –benzene C6H5Br = bromobenzene C6H5NO2 = nitrobenzene, and C6H5CH2CH2CH3 is propylbenzene

The Phenyl Group When a benzene ring is a substituent, the term phenyl is used (for C6H5—) You may also see “Ph” or “f” in place of “C6H5” “Benzyl” refers to “C6H5CH2—”

Disubstituted Benzenes Relative positions on a benzene ring ortho- (o) substituents on adjacent carbons (1,2) meta- (m) substituents separated by one carbon (1,3) para- (p) substituents separated by two carbons (1,4) Describes reaction patterns (“occurs at the para position”)

Benzene’s Unusual Structure All its C-C bonds are the same length: 139 pm — between single (154 pm) and double (134 pm) bonds Electron density in all six C-C bonds is identical Structure is planar, hexagonal C–C–C bond angles 120° Each C is sp2 and has a p orbital perpendicular to the plane of the six-membered ring

Naming Benzenes with More Than Two Substituents Choose numbers to get lowest possible values List substituents alphabetically with hyphenated numbers Common names, such as “toluene” can serve as root name (as in TNT)

5.3 Electrophilic Aromatic Substitution Reactions: Bromination Benzene is aromatic: a cyclic conjugated compound with 6  electrons Reactions of benzene lead to the retention of the aromatic core

5.3 Electrophilic Aromatic Substitution Reactions: Bromination Benzene’s  electrons participate in a nucleophilic fashion as a Lewis base in reactions with Lewis acids The product is formed by loss of a proton, which is replaced by bromine FeBr3 is added as a catalyst to polarize the bromine reagent (AlBr3 behaves similarly)

Addition Intermediate in Bromination The addition of bromine occurs in two steps In the first step the  electrons act as a nucleophile toward Br2 (in a complex with FeBr3) This forms a cationic addition intermediate from benzene and a bromine cation The intermediate is not aromatic and therefore high in energy

Electrophilic Bromination: Energy Diagram

Formation of Product from Intermediate The cationic addition intermediate transfers a proton to FeBr4- This restores aromaticity (in contrast with addition in alkenes)

5.4 Other Aromatic Substitutions 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 or AlCl3 Iodine must be oxidized to form a more powerful I+ species (with Cu+ or peroxide)

Aromatic Nitration The combination of nitric acid and sulfuric acid produces NO2+ (nitronium ion) The reaction with benzene produces nitrobenzene

Aromatic Sulfonation Substitution of H by SO3H (sulfonation) Reaction with a mixture of sulfuric acid and SO3 Reactive species is sulfur trioxide or its conjugate acid This process is an equilibrium

5.5 The Friedel–Crafts Alkylation and Acylation Reactions Alkylation is among the most useful electrophilic aromatic subsitution reactions Aromatic substitution of R+ for H+ Aluminum chloride promotes the formation of the carbocation

Limitations of the Friedel-Crafts Alkylation Only alkyl halides can be used (F, Cl, I, Br) Aryl halides and vinylic halides do not react (their carbocations are too hard to form) Will not work with rings containing an amino group substituent or a strongly electron-withdrawing group

Acylation of Aromatic Rings Reaction of an acid chloride (RCOCl) and an aromatic ring in the presence of AlCl3 introduces an acyl group, COR Benzene with acetyl chloride yields acetophenone

5.6 Substituent Effects in Electrophilic Aromatic Substitution Substituents can cause a compound to be (much) more or (much) less reactive than benzene Substituents affect the orientation of the reaction as well – the positional relationship is controlled ortho- and para-directing activators, ortho- and para-directing deactivators, and meta-directing deactivators

5.7 An Explanation of Substituent Effects Activating groups donate electrons into the ring, stabilizing the intermediate carbocation Deactivating groups withdraw electrons from the ring, destabilizing the carbocation intermediate

Ortho- and Para-Directing Activators: Alkyl Groups Alkyl groups activate: direct further substitution to positions ortho and para to themselves Alkyl group is most effective in the ortho and para positions

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

Ortho- and Para-Directing Deactivators: Halogens Electron-withdrawing inductive effect outweighs weaker electron-donating resonance effect – making halogens deactivators Resonance effect is only at the ortho and para positions, stabilizing carbocation intermediate

Meta-Directing Deactivators Inductive and resonance effects reinforce each other Ortho and para intermediates destabilized by deactivation of carbocation intermediate Resonance cannot produce stabilization

Summary Table: Effect of Substituents in Aromatic Substitution

Summary Graph

5.8 Oxidation and Reduction 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

5.8 Oxidation and Reduction of Aromatic Compounds Just as aromatic rings are inert to oxidation,they are also inert to reduction under typical alkene conditions High temperatures and pressures are required in order to reduce aromatic rings.

5.9 Other Aromatic Compounds Aromatic compounds can have rings that share a set of carbon atoms (fused rings) Compounds from fused benzene or aromatic heterocycle rings are themselves aromatic

Naphthalene Orbitals Three resonance forms and delocalized electrons

5.9 Other Aromatic Compounds Heterocyclic compounds contain elements other than carbon in a ring, such as N,S,O,P Aromatic compounds can have elements other than carbon in the ring There are many heterocyclic aromatic compounds and many are very common Cyclic compounds that contain only carbon are called carbocycles Nomenclature is specialized

Pyridine A six-membered heterocycle with a nitrogen atom in its ring  electron structure resembles benzene (6 electrons) The nitrogen lone pair electrons are not part of the aromatic system (perpendicular orbital) Pyridine is a relatively weak base compared to normal amines but protonation does not affect aromaticity

Pyrrole A five-membered heterocycle with one nitrogen Four sp2-hybridized carbons with 4 p orbitals perpendicular to the ring and 4 p electrons Nitrogen atom is sp2-hybridized, and lone pair of electrons occupies a p orbital (6  electrons) Since lone pair electrons are in the aromatic ring, protonation destroys aromaticity, making pyrrole a very weak base

5.10 Organic Synthesis Organic synthesis creates molecules by design Synthesis can produce new molecules that are needed as drugs or materials Syntheses can be designed and tested to improve efficiency and safety for making known molecules Highly advanced synthesis is used to test ideas and methods, answering challenges Chemists who engage in synthesis may see some work as elegant or beautiful when it uses novel ideas or combinations of steps – this is very subjective and not part of an introductory course

Synthesis as a Tool for Learning Organic Chemistry In order to propose a synthesis you must be familiar with reactions What they begin with What they lead to How they are accomplished What the limitations are A synthesis combines a series of proposed steps to go from a defined set of reactants to a specified product Questions related to synthesis can include partial information about a reaction of series that the student completes

Strategies for Synthesis Compare the target and the starting material Consider reactions that efficiently produce the outcome. Look at the product and think of what can lead to it Read the practice problems in the text

Synthesizing a Substituted Aromatic Compound Synthesize p-bromobenzoic acid starting from benzene. Strategy: Work backward by first asking, “What is an immediate precursor of p-bromobenzoic acid?”. Continue this process until benzene is the starting material. Note: There is usually more than one synthetic route possible.

Synthesizing a Substituted Aromatic Compound: Solution Two workable routes are possible.