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9 Introduction to Organic Chemistry 2 ed William H. Brown 9-1 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Aromatic Compounds Chapter 9 9-2 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Benzene - Kekulé • The first structure for benzene was proposed by August Kekulé in 1872 H H H C H C C C C C H H H H C H C C C C C H H H • this structure, however, did not account for the unusual chemical reactivity of benzene 9-3 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 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 and H-C-C bond angles 120° H 120° H C 1.09 Å H 120° C 120° C C C H 1.39 Å C- sp 2 -sp 2 CH sp 2 -1s H 9-4 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 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 H H C H C C C C H H C H 9-5 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 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 9-6 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Benzene - Resonance • Resonance 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 9-7 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Benzene - Resonance Ni +H2 1-2 atm. Cyclohexene + 3 H2 Benzene DH° = -28.6 kcal/mol (-120 kJ/mol) Cyclohexane Ni 200-300 atm Cyclohexane DH° = -49.8 kcal/mol (-208 kJ/mol) • comparing 3 x DH° for cyclohexene with DH° for benzene, it is estimated that the resonance energy of benzene is approximately 36 kcal/mol 9-8 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Heterocyclic Aromatics • Heterocyclic compound: contains one or more atoms other than carbon in a ring • Pyridine and pyrimidine are heterocyclic analogs of benzene. Each is aromatic. 4 4 3 5 6 2 6 •• 5 3 N N1 2 N1 •• Pyridine Pyrimidine •• 9-9 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Pyridine • Pyridine has a resonance energy of 32 kcal/mol, slightly less than that of benzene this sp2 hybrid orbital is perpendicular to the six • • • 2p orbitals of the pi system • • • N this pair of electrons is not a part of the aromatic sextet 9-10 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 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 this pair of electrons is a part of the aromatic sextet • • • • O this pair of electrons is not 9-11 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Other Heterocyclics CH 2 CH2 NH 2 HO N H Indole N H Serotonin (a neurotransmitter) NH 2 N N N H Purine N N N N N H Adenine Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9-12 9 Nomenclature • Monosubstituted alkylbenzenes are named as derivatives of benzene • many common names are retained CH 2 CH 3 Benzene Ethylbenzene CH3 Toluene CH(CH 3 ) 2 Cumene CH=CH 2 Styrene 9-13 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Nomenclature • these common names are also retained OH Phenol Aniline CHO Benzaldehyde NH 2 CO2 H Benzoic acid OCH 3 Anisole 9-14 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Nomenclature • benzyl and phenyl groups CH 3 Benzene Phenyl group C 6 H5 Benzyl group CH 3 C C H3 C Toluene CH 2 - C 6 H5 CH 2 Cl H Benzyl chloride (Z)-2-Phenyl-2-butene 9-15 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Disubstituted Benzenes • Locate 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 CH3 NH2 CO2 H NO2 Cl Br 4-Bromotoluene (p-Bromotoluene) 3-Chloroaniline 2-Nitrobenzoic acid (m-Chloroaniline) (o-Nitrobenzoic acid) 9-16 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Disubstituted Benzenes • where neither group imparts a special name, locate the groups and list them in alphabetical order CH 2 CH 3 4 3 NO 2 2 Br 1 2 1 Cl 1-Chloro-4-ethylbenzene (p-Chloroethylbenzene) 1-Bromo-2-nitrobenzene (o-Bromonitrobenzene) 9-17 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 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 NO2 OH 4 Br 6 1 2 Br 5 3 3 5 4 Br 2,4,6-Tribromophenol 2 6 1 Br CH 2 CH 3 2-Bromo-1-ethyl-4-nitrobenzene 9-18 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 PAHs • Polynuclear aromatic hydrocarbons (PAHs) contain two or more aromatic rings, each pair of which shares two ring carbons Naphthalene Anthracene Phenanthrene 9-19 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 PAHs Benzo[a]pyrene Coronene 9-20 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Phenols • The functional group of a phenol is an -OH group bonded to a benzene ring OH OH OH OH OH CH 3 OH Phenol 3-Methylphenol 1,2-Benzenediol 1,4-Benzenediol (m-Cresol) (Catechol) (Hydroquinone) 9-21 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Acidity of Phenols • Phenols are significantly more acidic than alcohols, compounds that also contain the -OH group Phenol: pKa = 9.95 - OH + H2 O O Ethanol: pKa = 15.9 CH 3 CH 2 OH + H2 O CH 3 CH 2 O + H 3 O+ - + H 3 O+ 9-22 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 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 9-23 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Acidity of Phenols •• O •• •• •• •• •• O O •• •• •• O •• •• H •• •• These 2 Kekulé structures are equivalent O •• H H •• These three contributing structures delocalize the negative charge onto carbon atoms of the ring 9-24 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Acidity of Phenols • Ring substituents, particularly halogen and nitro groups, have marked effects on the acidity of phenols OH Phenol pKa 9.95 OH Cl p-Chlorophenol pKa 9.18 OH NO2 p-Nitrophenol pKa 7.15 9-25 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Acidity of Phenols • Phenols are weak acids and react with strong bases to form water-soluble salts • water-insoluble phenols dissolve in NaOH(aq) OH Phenol pKa = 9.95 (stronger acid) + NaOH Sodium hydroxide (stronger base) O- Na + + H2 O Water Sodium phenoxide pKa = 15.7 (weaker base) (weaker acid) 9-26 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Acidity of Phenols • most phenols do not react with weak bases such as NaHCO3; they do not dissolve in aqueous NaHCO3 OH + Phenol pKa = 9.95 (Weaker acid) NaHCO 3 Sodium bicarbonate (Weaker base) O Na + + Sodium phenoxide (Stronger base) H2 CO3 Carbonic acid pKa = 6.36 (Stronger acid) 9-27 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Benzylic Oxidation • Benzene is unaffected by strong oxidizing agents such as H2CrO4 and KMnO4 • 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 O2 N Cl CH 3 2-Chloro-4-nitrotoluene K2 Cr 2 O7 H 2 SO4 O2 N Cl CO2 H 2-Chloro-4-nitrobenzoic acid 9-28 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Benzylic Oxidation • if there is more than one alkyl group, each is oxidized to a -CO2H group H3 C CH3 K2 Cr 2 O7 1,4-Dimethylbenzene (p-xylene) H2 SO4 O HOC O COH 1,4-Benzenedicarboxylic acid (terephthalic acid) 9-29 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Rexns of Benzene • The most characteristic reaction of aromatic compounds is substitution at a ring carbon Halogenation: H + Cl 2 FeCl 3 Cl + HCl Chlorobenzene Nitration: H + HNO 3 H2 SO 4 NO2 + H2 O Nitrobenzene 9-30 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Rexns of Benzene Sulfonation: H2 SO 4 H + SO 3 SO 3 H Benzenesulfonic acid Alkylation: AlX 3 H + RX R + HX An alkylbenzene Acylation: O H + RCX O A lX3 CR + HX An acylbenzene 9-31 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Rexns of Benzene - EAS • Electrophilic aromatic substitution: a reaction in which a hydrogen atom of an aromatic ring is replaced by an electrophile H + + E E + H + • We study • several common types of electrophiles, • how each is generated, and • the mechanism by which it replaces hydrogen 9-32 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Chlorination • Halogenation requires a Lewis acid catalyst, such as AlCl3 or FeCl3 • Step 1: formation of a chloronium ion Cl Cl Cl •• •• •• •• •• •• + Fe Cl chloronium ion Cl Cl •• •• Cl Fe + Cl Fe Cl4 •• Cl •• •• •• + •• Cl •• Cl 9-33 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Chlorination • Step 2: attack of the chloronium ion on the ring to give a resonance-stabilized cation intermediate + Cl + + rate-limiting step H H H + Cl Cl + Cl Resonance-stabilized cation intermediate 9-34 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Chlorination • Step 3: proton transfer to regenerate the aromatic character of the ring Cl FeCl3 + H fast Cl + HCl + FeCl3 Cl Cation Chlorobenzene intermediate • The mechanism for bromination is the same as that for chlorination 9-35 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 EAS: General Mechanism • A general mechanism Step 1: + H + E ratelimiting step Electrophile + Step 2: H E fast + H E Resonance-stabilized cation intermediate E + H+ • General question: what is the electrophile in an EAS and how is it generated? 9-36 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Nitration • The electrophile is NO2+, generated as follows H + H O NO2 + HSO 4 •• •• H O NO2 + H O SO 3 H •• Nitric acid H O •• •• NO2 + •• + O=N=O Nitronium ion •• •• •• H •• H H +O 9-37 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Nitration • The particular value of nitration is that the nitro group can be reduced to a 1° amino group O2 N CO 2 H + 3 H 2 Ni (3 atm) 4-Nitrobenzoic acid H2 N CO2 H + 2 H2 O 4-Aminobenzoic acid 9-38 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Friedel-Crafts Alkylation • Friedel-Crafts alkylation forms a new C-C bond between a benzene ring and an alkyl group CH3 + Benzene CH3 CHCl AlCl 3 2-Chloropropane (Isopropyl chloride) CH( CH 3 ) 2 + HCl Cumene (Isopropylbenzene) 9-39 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Friedel-Crafts Alkylation • Step 1: formation of an alkyl cation as an ion pair Cl •• R •• Cl •• + Al Cl Cl + •• R Cl - Cl Al Cl •• Cl + - R A lCl4 An ion pair containing a carbocation 9-40 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Friedel-Crafts Alkylation • Step 2: attack of the alkyl cation on the aromatic ring + R+ + H R + H H R + R The positive charge is delocalized onto three atoms of the ring 9-41 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Friedel-Crafts Alkylation • Step 3: proton transfer to regenerate the aromatic character of the ring + Cl A lCl 3 H R R + A lCl 3 + HCl 9-42 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Friedel-Crafts Acylation • Friedel-Crafts acylation forms a new C-C bond between a benzene ring and an acyl group O O + CH 3 CCl Benzene Acetyl chloride AlCl3 CCH3 + HCl Acetophenone 9-43 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Friedel-Crafts Acylation • the electrophile is an acylium cation O •• •• R- C Cl •• + Cl A l- Cl Cl O R- C + •• Cl - Cl A l Cl •• Cl O R- C+ A lCl 4 An ion pair containing an acylium ion 9-44 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Other Alkylations • Carbocations are generated by • treatment of an alkene with a protic acid, most commonly H2SO4, H3PO4, or HF/BF3 + CH3 CH= CH2 Benzene Propene (Propylene) H3 PO4 CH( CH3 ) 2 Isopropylbenzene (Cumene) 9-45 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Other Alkylations • by treating an alkene with a Lewis acid A lCl 3 + Benzene Cyclohexene Phenylcyclohexane • and by treating an alcohol with H2SO4 or H3PO4 H 3 P O4 C( CH3 ) 3 + H2 O + ( CH3 ) 3 COH Benzene tert-Butyl alcohol tert-Butylbenzene 9-46 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Disubstitution • Existing 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 or meta directing 9-47 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 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 • activating toward further substitution, or • deactivating 9-48 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Disubstitution • -OCH3 is ortho-para directing OCH 3 Br 2 CH 3 CO2 H Anisole OCH 3 OCH 3 Br + o-Bromoanisole (4%) + HBr Br p-Bromoanisole (96%) 9-49 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Disubstitution • -NO2 is meta directing NO2 + HNO 3 H2 SO4 NO2 NO2 NO2 NO2 Nitrobenzene + + NO2 m-Dinitrobenzene (93%) o-Dinitrobenzene NO2 p-Dinitrobenzene Less than 7% combined 9-50 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. Strongly activating Moderately activating Weakly activating •• NH 2 •• NHR O •• NR2 NHCR •• •• •• OH O O •• •• •• •• •• •• OCAr OCR R •• Br •• •• I •• Cl •• •• •• •• •• •• Weakly deactivating ••F OR Impotance in Directing Ortho-para Directing 9 Disubstitution •• 9-51 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. O O O O CR COH COR Moderately CH O deactivating O SOH C N CNH 2 O Strongly deactivating NO2 NH 3 + CF3 CCl3 Impotance in Directing Meta Directing 9 Disubstitution 9-52 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 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 9-53 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Disubstitution CH 3 CO2 H HNO 3 K 2 Cr 2 O7 H 2 SO 4 H 2 SO 4 CH 3 NO2 NO2 p-Nitrobenzoic acid CO2 H CO 2 H K 2 Cr 2 O7 HNO 3 H 2 SO 4 H 2 SO 4 NO2 m-Nitrobenzoic acid 9-54 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 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 9-55 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 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 9-56 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Theory of Directing Effects • -OCH3; assume meta attack OCH 3 + NO 2 + OCH 3 + H NO 2 (a) slow OCH 3 + H H NO 2 + NO 2 (b) OCH 3 OCH 3 fast -H + NO 2 (c) 9-57 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Theory of Directing Effects • -OCH3: assume ortho-para attack 9-58 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Theory of Directing Effects • -NO2; assume meta attack NO 2 + NO 2 + NO 2 NO 2 + H NO 2 (a) slow NO 2 NO 2 + H NO 2 (b) H + NO 2 (c) fast -H + NO 2 9-59 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Theory of Directing Effects • -NO2: assume ortho-para attack 9-60 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved. 9 Aromatic Compounds End Chapter 9 9-61 Copyright © 2000 by John Wiley & Sons, Inc. All rights reserved.