9 9-1 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Introduction to Organic Chemistry 2 ed William H. Brown

9 9-2 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. AromaticCompounds Chapter 9

9 9-3 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Benzene - Kekulé The first structure for benzene was proposed by August Kekulé in 1872 this structure, however, did not account for the unusual chemical reactivity of benzene

9 9-4 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Benzene - VB Model The concepts of hybridization of atomic orbitals and the theory of resonance, developed in the 1930s, provided the first adequate description of benzene’s structure the carbon skeleton is a regular hexagon, with all C- C-C and H-C-C bond angles 120°

9 9-5 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Benzene - VB Model each carbon has one unhybridized 2p orbital containing one electron overlap of the six parallel 2p orbitals forms a continuous pi cloud the electron density of benzene lies in one torus above the plane of the ring and a second below it

9 9-6 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Benzene - Resonance We often represent benzene as a hybrid of two equivalent Kekulé structures each makes an equal contribution to the hybrid, and thus the C-C bonds are neither double nor single, but something in between

9 9-7 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Benzene - Resonance Resonance energyResonance energy: the difference in energy between a resonance hybrid and the most stable of its hypothetical contributing structures in which electrons are localized on particular atoms and in particular bonds One way to estimate the resonance energy of benzene is to compare the heats of hydrogenation of benzene and cyclohexene

9 9-8 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Benzene - Resonance comparing 3 x  H° for cyclohexene with  H° for benzene, it is estimated that the resonance energy of benzene is approximately 36 kcal/mol

9 9-9 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Heterocyclic Aromatics Heterocyclic compoundHeterocyclic compound: contains one or more atoms other than carbon in a ring Pyridine and pyrimidine are heterocyclic analogs of benzene. Each is aromatic.

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Pyridine Pyridine has a resonance energy of 32 kcal/mol, slightly less than that of benzene

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Furan Of the two unshared pairs of electrons on the oxygen atom of furan, one is and one is not a part of the aromatic sextet the resonance energy of furan is 16 kcal/mol

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Other Heterocyclics

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature Monosubstituted alkylbenzenes are named as derivatives of benzene many common names are retained

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature these common names are also retained

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nomenclature benzyl and phenyl groups

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Disubstituted Benzenes orthometaparaLocate the two groups by numbers or by the locators ortho (1,2-), meta (1,3-), and para (1,4-) where one group imparts a special name, name the compound as a derivative of that molecule

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Disubstituted Benzenes where neither group imparts a special name, locate the groups and list them in alphabetical order

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Polysubstituted Derivs if one group imparts a special name, name the molecule as a derivative of that compound if no group imparts a special name, list them in alphabetical order, giving them the lowest set of numbers

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. PAHs Polynuclear aromatic hydrocarbons (PAHs) contain two or more aromatic rings, each pair of which shares two ring carbons

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. PAHs

Phenols The functional group of a phenol is an -OH group bonded to a benzene ring

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Acidity of Phenols Phenols are significantly more acidic than alcohols, compounds that also contain the -OH group

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Acidity of Phenols We account for the increased acidity of phenols relative to alcohols in the following way delocalization of the negative charge on a phenoxide ion stabilizes it relative to an alkoxide ion because a phenoxide ion are more stable than an alkoxide ion, phenols are stronger acids than alcohols Note that while this reasoning helps us to understand why phenols are more acidic than alcohols, it does not give us any way to predict how much stronger they are

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Acidity of Phenols

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Acidity of Phenols Ring substituents, particularly halogen and nitro groups, have marked effects on the acidity of phenols

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Acidity of Phenols Phenols are weak acids and react with strong bases to form water-soluble salts water-insoluble phenols dissolve in NaOH(aq)

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Acidity of Phenols most phenols do not react with weak bases such as NaHCO 3 ; they do not dissolve in aqueous NaHCO 3

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Benzylic Oxidation Benzene is unaffected by strong oxidizing agents such as H 2 CrO 4 and KMnO 4 halogen and nitro substituents are unaffected by these reagents an alkyl group with at least one hydrogen on the benzylic carbon are oxidized to a carboxyl group

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Benzylic Oxidation if there is more than one alkyl group, each is oxidized to a -CO 2 H group

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Rexns of Benzene The most characteristic reaction of aromatic compounds is substitution at a ring carbon

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Rexns of Benzene

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Rexns of Benzene - EAS Electrophilic aromatic substitutionElectrophilic aromatic substitution: a reaction in which a hydrogen atom of an aromatic ring is replaced by an electrophile We study several common types of electrophiles, how each is generated, and the mechanism by which it replaces hydrogen

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Chlorination Halogenation requires a Lewis acid catalyst, such as AlCl 3 or FeCl 3 Step 1: formation of a chloronium ion

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Chlorination Step 2: attack of the chloronium ion on the ring to give a resonance-stabilized cation intermediate

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Chlorination Step 3: proton transfer to regenerate the aromatic character of the ring The mechanism for bromination is the same as that for chlorination

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. EAS: General Mechanism A general mechanism General question: what is the electrophile in an EAS and how is it generated?

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nitration The electrophile is NO 2 +, generated as follows

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Nitration The particular value of nitration is that the nitro group can be reduced to a 1° amino group

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Friedel-Crafts Alkylation Friedel-Crafts alkylation forms a new C-C bond between a benzene ring and an alkyl group

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Friedel-Crafts Alkylation Step 1: formation of an alkyl cation as an ion pair

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Friedel-Crafts Alkylation Step 2: attack of the alkyl cation on the aromatic ring

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Friedel-Crafts Alkylation Step 3: proton transfer to regenerate the aromatic character of the ring

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Friedel-Crafts Acylation Friedel-Crafts acylation forms a new C-C bond between a benzene ring and an acyl group

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Friedel-Crafts Acylation the electrophile is an acylium cation

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Other Alkylations Carbocations are generated by treatment of an alkene with a protic acid, most commonly H 2 SO 4, H 3 PO 4, or HF/BF 3

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Other Alkylations by treating an alkene with a Lewis acid and by treating an alcohol with H 2 SO 4 or H 3 PO 4

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Disubstitution orientationrateExisting groups on benzene ring influence further substitution in both orientation and rate Orientation: certain substituents direct preferentially to ortho & para positions; others direct preferentially to meta positions substituents are classified as either ortho-para directing meta directing ortho-para directing or meta directing

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Disubstitution Rate: certain substituents cause the rate of a second substitution to be greater than that for benzene itself; others cause the rate to be lower substituents are classified as activatingactivating toward further substitution, or deactivatingdeactivating

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Disubstitution -OCH 3 is ortho-para directing

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Disubstitution -NO 2 is meta directing

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Disubstitution

Disubstitution

Disubstitution From the information in Table 9.2, we can make these generalizations alkyl groups, phenyl groups, and all groups in which the atom bonded to the ring has an unshared pair of electrons are ortho-para directing. All other groups are meta directing all ortho-para directing groups except the halogens are activating toward further substitution. The halogens are weakly deactivating

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Disubstitution

Theory of Directing Effects The rate of EAS is limited by the slowest step in the mechanism for almost every EAS, the rate-limiting step is attack of E + on the aromatic ring to form a resonance-stabilized cation intermediate the more stable this cation intermediate, the faster the rate-limiting step and the faster the overall reaction

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Theory of Directing Effects For ortho-para directors, ortho-para attack forms a more stable cation than meta attack ortho-para products are formed faster than meta products For meta directors, meta attack forms a more stable cation than ortho-para attack meta products are formed faster than ortho-para products

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Theory of Directing Effects -OCH 3 ; assume meta attack

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Theory of Directing Effects -OCH 3 : assume ortho-para attack

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Theory of Directing Effects -NO 2 ; assume meta attack

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Theory of Directing Effects -NO 2 : assume ortho-para attack

Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. AromaticCompounds End Chapter 9