51862392 027 aromatic chemistry

8/2/2019 51862392 027 Aromatic Chemistry

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Cover images0 urray Robertsonhisual elements 1998-99, taken from the109Visual Elements Periodic Table, available at www.chemsoc.org/viselements

ISBN 0-85404-662-3A catalogue record for this book is available from the British Library0 he Royal Society of Chemistry 2002All rights reservedApart i om unjjh ir dealingfor the purposes of research or private study, or criticism orreview as perm itted under the terms of th e U K Copjright, Designs and Patents Ac t,1988, thispuhlication n?aj? ot he reproduced, Jtored or transmitted, in any form or byanymeans, without th e prior permission in w riting of Th e Roycrl Society of Chemistry,or in the cuse of reprographic reproduction only in accordance wiith the terms of th elicenc es issued by the Copyright Licensing Agency in the U K , or in accordance with thet e r m of the licences issued by the appropriate Reproduction R ights Orgunization out-side the UK. Enq uiritv concerning reproduction ou tside the terms stated here should hesent fo The Roy d Soc ie ty of Chemistry at the addressprinted on this page.Published by The Royal Societyof Chemistry. Thomas Graham House, Science Park,Milton Road, Cambridge CB4 OWF,UKRegistered Charity No. 207890For further information see our web site at www.rsc.orgTypeset in Great Britain by Wyvern 21, BristolPrinted and bound by Polestar Wheatons Ltd, Exeter


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Preface

Aro matic chemistry, in terms of the production of derivatives of benzeneand, to a less extent, other carbocyclic aromatic compounds, is ofimmense industrial importance and is the mainstay of many chemicalcompanies. Derived p roduc ts ar e in general use across such diverse indus-tries as pharmace uticals, dyestuffs, an d polymers.The aromatic chemistry required by an undergraduate in chemistry,biochemistry, m aterials science an d related disciplines is assem bled in thistext, which also provides a link to o the r aspects of o rganic chemistry an da platform for further study. In line with the series style, a number ofworked problems and a selection of questions designed to help the stu-dent to unde rstand the principles described are included.

Th e first ch ap ter discusses the concept of aromaticity, after which thereis a description of aromatic substitution reactions. Ch apter s covering thechemistry of the major functionalized derivatives of benzene follow. Achapter on the use of metals in aromatic chemistry discusses not only thechemistry of Gr igna rd reagents and aryllithium com pou nds but also themore recent uses of transition metals in the synthesis of aromatic com-pounds. T he penultimate chapt er discusses the oxidation a nd reduction ofthe benzene ring an d the text concludes with the chemistry of som e poly-cyclic com poun ds.We have chosen to use the names of chemicals that are in commonusage on the basis that stu den ts should then be able to read a nd make useof the ch em icd literature and also to locate chemicals in the laboratory.Systematic names ar e given in parentheses at the first ap pro priate opp or -tunity. Ideally, a student shou ld be able to use bot h systems interchange-ably without difficulty. Th e R SC website has a n Appendix of Co mm onand Systematic Names (http://www.chemsoc.org/pdf/tct/functionalap-pendix.pdf) to which students a re referred. A Fu rth er Reading list is alsoavailable at (http://www.chemsoc.org/pdf/tct/functionalreading.pd~.We are grateful to Dr. M ark Heron for his valuable comm ents o n thedraft manuscript and to D r. Alan Jones and Ms. Beryl Newel1 for theirhelp in preparation of the final manuscript. Mr. Martyn Berry andProfessor Alwyn Davies FRS offered advice, encouragement and criti-cism throughou t the preparation of the text which were mo st appreciated.Mrs. Janet Freshwater of the Royal Society of Chemistry was involved inthe project from start to finish and we thank her for her efficiency andguidance. We thank ou r wives, Annabelle, M argaret an d A nita, for theirhelp, patience and understanding dur ing the writing of this book .

J. D. Hepworth, Universityqf Central LancashireD. R . Waring, formerly of Kodak Ltd., Kirkby, LiverpoolM . J. Waring, AstraZenecu, Alderley Park, Cheshire


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L U I 1 OR - IN - C ti I t tProfessor E W Ahel

r x r c u T i v t L D I T O K SProfl.ssor A G DavirsPrqfl.ssor D PhillipsProfessor J D Woollins

L: D U CAT I0N A L C O N S CI L TA N TM r M Berry

This series of books consists of sh ort, single-topic or m odular texts, concentrating on the funda-men tal areas of chemistry tau ght in underg raduate science courses. Each bo ok provides aconcise account o f the basic principles underlying a given subject, embodying an independent-learning philosophy and including worked examples. The o ne topic, one book approach ensuresthat the series is adaptab le to chemistry courses across a variety of institution s.T I T L E S I N T H E S E R I E S

Stereochemistry D G MorrisReactions and C haracterization of SolidsMain Gro up Chemistry WHendersond- and f-Block Chemistry C J JoncsStructure and Bonding J Burvc.frFunctional Grou p Chemistry J R HimsonOrganotransition Metal Chemistry A F HillHeterocyclic Chem istry M Sriinshurj9Atomic Structure and Periodicity J BarrettThermodynam ics and Statistical MechanicsBasic Atomic and Molecular SpectroscopyOrganic Synthetic Metho ds J R HunsonAromatic ChemistryQuan tum Mechanics for Chemists

S E Dann

J M Soddon & J D GaleJ A4 Hollas

J D Hepivorth, D R Wuring& M J WaringD 0 Hay\tard

FO R T H C O M I N Ci T I T L E S

Mechanisms in Organic ReactionsMolecular InteractionsReaction KineticsX-ray CrystallographyLanthanid e and Actinide ElementsMaths for ChemistsBioinorganic ChemistryChemistry of Solid SurfacesBiology for Chem istsMulti-e lement N M RPeptides and ProteinsBiophysical ChemistryNatural P roduct: The SecondaryMetabolites

Furtlier inforniution about this series is uvailahle at \vivtr. cliernsoc.orgltctOrders und cnyuiries should he sent to:Sales and Custom er Care, Royal Society of Chem istry, Thom as Gr aha m House,Science Park, Milton Road, Cam bridge CB 4 OWF, U KTel: +44 1223 432360; Fax: + 44 1223 426017; Email: [email protected]


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Contents

I . 1 Introduction1.2 Structure of Benzene1.31.4 Th e Huckel RuleI . 5 Nomenclature

Stability of the Benzene Ring

2.1 Introduction2.2 Electrophilic Arom atic Substitution (SEA r)2.32.4 The Ham mett Equation2.5 Nucleophilic Arom atic Substitution2.6 ips0 Substitution

Reactivity an d Orie ntatio n in Electrophilic Arom aticSubstitution

3.1 Introduction3.2 Source of Alkylbenzenes3.3 Introduction of Alkyl Grou ps3.4 Reactions of Alkylbenzenes3.5 Aryl Derivatives of Benzene

1225

11

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vi Contents

4.14.24.34.44.54.64.7

5.15.25.35.45.55.6

6.16.26.36.4

7.17.27.37.47.5

8.18.28.38.48.58.6

IntroductionIndustrial Synthetic M ethodsLaboratory SynthesesTh e Acidity of PhenolsReactions of the Hydroxy Gr ou pReactions of the RingDihydroxybenzenes

IntroductionIntroduction of Acidic G roup sReactions of Arom atic AcidsAcidity of Arom atic AcidsComp ounds with M ore Than One Acidic Gro upSide-chain Acids

IntroductionAromatic AlcoholsArom atic AldehydesAromatic Ketones

IntroductionIntroduction of the Nitro Gr ou pCharge T ransfer Com plexesReactions of Nitro Com poundsNitrosobenzene and Phenylhydroxylamine

IntroductionIntroduction of the Amino Grou pReactions of Arom atic AminesRelated CompoundsBasicity of AminesDiazonium Salts

47474850515355

585860636465

67676876

7979838385

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Contents vii

9.1 Introduction 1049.2 Synthesis of Aryl Halides 1059.3 Reactions of Aryl Halides 1089.4 Aromatic Halogen Com poun ds Substituted in the SideChain 111

10.1 G rignard and Organ olithium Reagents10.2 Electrophilic Metallation10.3 Transition Metal Mediated Processes10.4 A ryl Cou pling Reactions10.5 Arene-Chromium Tricarbony l Comp lexes

11.1 Introduction11.2 Reduction of the Benzene RingI 1.3 Oxidation of the Benzene Ring

12.1 Introduction12.2 Chemistry of Naphthalene12.3 Chemistry of Anthracene12.4 Chemistry of Phenanthrene

114118119121125

129129131

13513514114 3


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Aromatici y

I. Introduction

00 0

The classification of organic compounds is based on the structure of themolecules. compounds have open-chain structures such asbonds. In molecules, the carbon atoms form a cyclic structure,as in cyclohexane (2) and cyclohexene (3).compounds are unsaturated cyclic molecules that possessadditional stability as a result of the arrangement of .Tc-electronsassociated with the unsaturation of the ring system. This book willconcentrate on the chemistry of benzene (4) and its derivatives andrelated polynuclear hydrocarbons. Aromatic compounds are also knownas ; they can be , indicating that the ring skeleton con-tains only carbon atoms, or , with at least one atom otherthan carbon in the ring. These heteroatoms are typically N, 0 or S.Heterocyclic compounds, which can be aromatic or alicyclic, are coveredin another book in this series.Initially, we will look at what distinguishes aromatic compounds fromother cyclic molecules and how chemists understanding of aromaticityhas developed up to the present day.

hexane (1) and can contain single (C-C), double (C=C) and triple (C=C) 1 2

3 4


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2 Aromatic Chemistry

5RI

7

MR

8

1.2 Structure of BenzeneBased on elemental composition and relative molecular mass determi-nations, the formula of benzene was found to be C,H,. The saturatedhyd roc arb on hexane has the molecular formula C,H,, and therefore itwas concluded that benzene was unsaturated. Kekule in 1865 proposedthe cyclic structu re 4 for benzene in which the car bon atom s were joinedby alternate single and double bonds. Certain reactions of benzene,such as the catalytic hydrogenation to cyclohexane, which involves theaddition of six hydrogen atoms, confirmed that benzene was a ringcompound and that i t contained three double bonds. However, sincebenzene did not undergo addition reactions with HCl and HBr, it wasconcluded that these double bonds were different from those in etheneand other unsaturated aliphatic compounds.

In 1867, Dew ar prop osed several possible structures for benzene, on eof which was 5 . However, in 1874, Ladenburg proved experimentallythat all the hydrogen atoms of benzene were equivalent and suggestedthe prismatic structure 6.Kekules proposed structure 4 looks more in keeping with o ur curre ntknowledge of benzene, although it does not explain how the doublebonds differ from the aliphatic type. Furthermore, although the twostructures 7 and 8 can be drawn for a 1,2-disubstituted benzene, onlyone such compound exists. Kekule proposed that the equivalent struc-tures 7 and 8 oscillated between each o ther , averaging o ut the single anddouble bonds so that the compounds were indistinguishable.1.3 Stability of the Benzene RingKekules proposals gained wide acceptance and were supported by theexperimental work of Baeyer in the late 19th century, but these ideas didnot explain the unusual stability of benzene. T his is typified by its chem-ical reactions, which are alm ost exclusively substitution rath er th an theexpected addition. Throughout this book there will be many examplesof this property. In addition, physical properties such as enthalpiesof hydrogenation and combustion are significantly lower than would beexpected for the cyclohexatriene structure of Kekule. The enthalpyof hydrogenation (AH) of the do ub le bond in cyclohexene is -120 kJmol-I and that of cyclohexa-1,3-diene with two double bonds is almosttwice that at -232 kJ mol I . Cyclohexatriene, if it existed, would beexpected to have an enthalpy of hydrogenation of three times the valueof cyclohexene, a AH of approximately -360 kJ mol - I . How ever, the valuefor benzene is less exothermic than this com par ison suggests, being on ly-209 kJ mol I . Thus benzene is 151 kJ mol- more stable than cyclo-hexatriene (Figure 1.1). This is known as the of ben-


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Aromaticity 3

zene or its . This stabilizing feature dominates the Figure 1.1 Hydrogenation ofchemistry of benzene a nd its derivatives. cyclohexene, cyclohexadiene andbenzene1.3.1 Valence Bond Theory of AromaticityX-ray crystallographic analysis indicated that benzene is a p lana r, regularhexagon in which all the carbo n-c arb on bon d lengths are 139 pm , inter-mediate between the single C-C bond in ethane (154 pm) and the C=Cbond in ethene (134 pm), and therefore all have some double bondcharac ter. Th us the representation of benzene by one Kekule structureis unsatisfactory. T he picture of benzene according to valence bond the-ory is a resonance hybrid of the two Kekule or canonical forms 4 and9, conventionally shown as in Figure 1.2, and so each carbon-carbonbond a pparent ly has a bond order of 1.5. Figure 1.2

4 9 10Kekulk structuresL J5 11 12Dewar structures


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4 Aromatic ChemistryAlthough th e canonical form s for benzene are imaginary an d d o notexist, the structure of benzene will be represented by one of the Kekulestructures throughout this book. This is common practice. A circle with-

in a hexagon a s in 10, symbolic of the n-cloud, is sometimes used t o rep-resent benzene.1.3.2 Molecular Orbital Theory of BenzeneThe curre nt understanding of the structure of benzene is based on molec-ular orbital ( M O ) theory. The six carbon atoms of benzene are sp2hybridized. Th e three sp hybrid o rbitals of each car bo n ato m , which arearrang ed at angles of 120, overla p with tho se of two other carbon atom sand w ith the s orbital of a hydrogen atom to form the planar o-bondedskeleton of the benzene ring. The p orbital associated with each carboncontains one electron and is perpendicular to the plane of the ring.M O theory tells us that the six parallel p atomic orbitals are com-bined together t o form six MOs, three of which are b onding orbitals a ndthree anti-bond ing. Figure 1.3 shows the relative energy levels of theseMOs. The six nele ctr on s occupy the three b onding orbitals, all of lowerenergy than the uncombined p orbitals; the higher energy anti-bondingMOs are empty.

Figure 1.3

Figure 1.4

This arrangement accounts for the extra stabili ty or aromaticity ofbenzene. The six overlapping p orbitals can be pictured as forming ax-electron cloud comprising of two rings (think of themas doughnuts!), one abo ve and one below the molecular plane as shownin Figure 1.4. There are n o localized C=C bond s as there ar e in alkenes.

The M Os of benzene are shown pictorially in Figure 1.5. Th e stabilityof a M O is related to the number of nodes it possesses; that is to say,the number of times the wave function changes phase (sign) around thering system. The most stable form has no nodes, when there is a bond-ing interaction between all six adjacent carbon atoms.


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Aromaticity 5

Figure 1.5

1.4 The Huckel RuleI t is im porta nt to exam ine arom aticity in its wider concept a t this point.There are many compounds and systems besides benzene that arearomatic. They possess common features in addition to planarityand aromatic stabili ty. M O calculations carried out by Hiickel in the1930s showed that aromatic character is associated with planar cyclicmolecules that contained 2, 6, 10, 14 (an d so on ) n;-electrons. Th is seriesof num bers is represented by the term 4n + 2, where n is an integer, andgave rise to H iickels 4n + 2 rule that refers to the numbe r of nelect ronsin the p-orbital system. In the case of benzene, n = 1, and thus the systemcontains six n-electrons that are distributed in M O s as shown above.


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6 Aromatic ChemistryThis rule is now an important criterion for aromaticity. Those systemsthat contain 4n n;-electrons are unstable and are referred to as ant i -aromatic compounds.Th e reason fo r the success of the Hiickel rule in predicting aromatic-ity lies in the derivation of th e 71: MOs. F o r cyclic conjugated molecules,the energy levels of the bonding M Os are always arra nged with o ne low-est-lying M O followed by degenerate pairs of orbitals. The anti-bondingorb itals are arra nge d inversely, with sets of two d egenerate levels and asingle highest energy orbital. In the case of benzene, it requires twoelectrons to f i l l the first M O and then four electrons to fill each of th e nsucceeding energy levels, as illustrated in Figure 1.3. A filled set of bond-in g M Os results in a stable system. This idea is very like that which linksthe stability of the noble gases to a filled set of atom ic orbitals.

Figure 1.6


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Aromaticity 7Although adherence to the H uckel rule is a valuable test for aromaticity,othe r properties are also used to assess whether a com pou nd is aro ma ticor no t. One such diagnostic tool is ' H N M R spectroscopy. When exposedto a magnetic field, the n-electron cloud circulates to produce a ringcurrent that generates a local magnetic field (Figure 1.7). This new fieldboosts the applied magnetic field outside the ring. As a result, thehydrogen atoms are deshielded and resonate at a lower applied field,usually in the range 6 6.5-8.5 ppm. Alkenyl hydrogen atoms are alsodeshielded, but to a lesser extent and normally resonate in the region 64.5-5.5 ppm. The local field inside the ring opposes the applied fieldand this effect is apparent in the 'H N M R spectra of the annulenes (seep. 11 ) .

1.4.1 2n-Electron SystemsAromatic systems that obey Hiickel's 4n + 2 rule where n = 0 and sopossess two n-electrons do exist and are indeed stable. The smallestpossible ring is three membered and the derived unsaturated struc ture iscyclopropene. The theoretical loss of a hydride ion from this moleculeleads to the cyclopropenyl cation, which contains two n-electronsdistributed over the three carbon atoms of the planar cyclic system(Figure 1.8).

Figure 1.7

Figure 1.8

This cationic species and a number of its derivatives have been pre-pared and they are quite stable, despite the strain associated with theinternal bond angles of only 60". Fo r example, the reaction of hydrogenbromide'with diphenylcyclopropenone, which is itself a stable com pou ndwith a rom atic chara cter , gives the diphenylcyclopropenium salt (Scheme1 . 1 ) .

Ph

ph)+Oh PhH Br * N O H r-

Scheme 1.1


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a Aromatic Chemistry

Scheme 1.2

Scheme 1.3

Examination of the cyclobutadiene system indicates that it possessesfour n-electrons and is thus an unstable 4n system. Cyclob utadiene itselfonly exists at very low temperatures, though some of its derivatives arestable to some extent at room temperature. Cyclobutadiene is a rectan-gular diene. Loss of two electrons throug h the departure of two chlorideions from the 3,4-dichlorocyclobutene derivative creates a 2n-electronarom atic system, the square, stable cyclobutenyl dication (Scheme 1.2).

MeFMeSbFsCl-I.,, I MeMe

I 4.2 6.n-Electron SystemsWe have seen that benzene fits into this category, but there are a num-ber of other stable aromatic systems that contain six n-electrons.Cyclopentadiene is surprisingly acidic (pKa ca. 16) for a hydrocarbon.This property arises because the cyclopentadienyl anion, generated byabstraction of a proton by a base such as sodium ethoxide (Scheme 1.3),has a delocalized aromatic set of six n-electrons.

The cyclopentadienyl anion 13 is an efficientlyin which all the carbon-carbon bond lengths are equal (Figure1.9). It forms stable compounds, of which ferrocene (14) is an example,which undergo aromatic substitution reactions such as sulfonation andace ylation. derived from cyclo-heptatriene that possesses the aromatic sextet of n-electrons. Tropyliumbromide is formed by the addition of bromine to cycloheptatriene and

In contrast, it is the

Figure 1.9


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Aromaticity 9then loss of hydrogen bromide by heating. I t can also be generated direct-ly from cycloheptatriene by hydride ion abstraction using triphenylcar-benium perchlorate (Scheme 1.4). In the tropylium ion 15, the bondlengths are equal and all seven carbon atoms share the positive charge(Figure 1.10).

H I

15 Scheme 1.4

Figure 1.10

Scheme 1.5


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I 0 Aromatic Chemistry

Figure 1.12

Azulene (16) is a stable, blue solid hydrocarbon that undergoes typicalelectrophilic aromatic substitution reactions. It may be regarded as acombination of 13and 15; in keeping with this it has a dipole momentof 0.8 D (Figure 1.11). The fusion bond linking the two rings is longer(150 pm) than the other bonds (139-140 pm), indicating that azulene isa peripherally conjugated system.

16

Figure 1.l

Some heterocyclic compounds possess aromatic character. One suchimportant compound is pyridine (17), in which one of the CH units ofbenzene has been replaced by a nitrogen atom (Figure 1.12). Althoughthe chemistry of pyridine shows several important differences frombenzene, it also has some common characteristics. The five carbon atomsand the nitrogen atom each provide one electron for the n-cloud, there-by conferring aromaticity on pyridine according to Huckels rule. Noticethat the nitrogen retains a lone pair of electrons in an sp2orbital directedaway from the ring; this accounts for the basic properties ofpyridine.

Similarly, the five-membered heterocycle pyrrole (18) is aromatic,although this molecule obeys Huckels rule only because the nitrogenatom contributes two electrons to the n-cloud. In this respect, pyrrole isanalogous to the cyclopentadienyl anion. As a consequence, the nitro-gen atom does not retain a lone pair of electrons and pyrrole is not basic.

1.4.3 1OX-, 147~-and 18lt-Electron SystemsThe most important 10n carbocyclic system is naphthalene (19) in whichtwo benzene rings are fused together. The fused systems anthracene (20)and phenanthrene (21) obey Huckels rule, where n = 3, and have 14n-electrons. All three compounds are typically aromatic and their chem-istry is similar to that of benzene, as discussed in Chapter 12.

19 20 21


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Aromaticity 11In 1962, Sondheimer prepared a series of conjugated monocyclic poly-enes called ,with the specific purpo se of testing Huckels rule.Amongst the annulenes prepared, compound 22 with 14 and compound

23 with 18 carbon atoms, that is n =3 and n = 4, respectively, have themagnetic properties required for aromatic cha racter, but behave chemi-cally like conjugated alkenes. In [18lannulene (23), the hydrogen atomson the outside of the ring resonate in the aromatic region at 6 9.3 ppm.How ever, the inner pro ton s lie in the region where the induced field asso-ciated with the ring current opposes the applied field. They are thereforeshielded and so resonate upfield at 6 -3.0 ppm.

22

I 5 Nomenclature 23Th e remainder of this book will be devoted to th e synthesis and reactionsof a range of aromatic compounds. It is important that you understandthe naming of these compounds. T he use of trivial names is widespread,particularly in the chemical industry; although some of the older nameshave disappeared from use, many persist and are allowed in the IU PA Csystem. Some of these are presented in Figure 1.13.

Monosubstituted compounds are commonly named as in aliphaticchemistry, with the substituents appearing as a prefix to the p arent namebenzene; bromobenzene, chlorobenzene and nitrobenzene are examples(Figure 1.14).

Figure 1.13

Figure 1.14

There are two acceptable ways of naming the three positional isomersthat are possible for disubstituted benzene rings. The substituent


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12 Aromatic Chemistrypositions 1,2-, 1,3- and 1,4- are sometimes replaced by the termsortho-, meta- and para- (abbreviated to 0-, - and p - , respectively) (see6;orth04 and 25). You are advised to become familiar with both systems sothat you can use them interchangeably.In multiply substituted compounds, the groups are numbered so thatthe lowest possible numbers are used. The substituents are then listed inalphabetical order with their appropriate numbers. Examples are givenin Figure 1.15, which also introduces further trivial names.

meta4 para24 25

Figure 1.15

There are occasions when the benzene ring is named as a substituentand in these cases the name for C,H,- is phenyl, abbreviated to Ph. Thename for C,H,CH,- is benzyl or Bn, whilst the benzoyl substituent isC,H,CO- or Bz. These substituents can also be named systematically asshown in Figure 1.16.

Figure 1.16


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Aromatic Substitution

2.1 IntroductionIn Chapter 1 it was stated that the principal reaction of benzene and itsderivatives is rather than addition. Indeed, electrophilic sub-stitution in aromatic systems is one of the most important reactions inchemistry and has many commercial applications.The nelectron cloud above and below the plane of the benzene ringis a source of electron density and confers nucleophilic properties on thesystem. Thus, reagents that are deficient in electron density, 9are likely to attack, whilst electron-rich nucleophiles should be repelledand therefore be unlikely to react. Furthermore, in electrophilic substi-tution the leaving group is a proton, H + ,but in nucleophilic substitutionit is a hydride ion, H-; the former process is energetically morefavourable. In fact, is not common,but it does occur in certain circumstances.

15


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2.2 Electrophilic Aromatic Substitution (SAr)In simple terms, electrophilic aromatic substitution proceeds in two steps.Initially, the electrophile E' adds to a carbon atom of the benzene ringin the same manner in which it would react with an alkene, but here then-electron cloud is disrupted in the process. However, in the second stepthe resultant carbocation eliminates a proton to regenerate the aromat-ic system (Scheme 2.1). The combined processes of addition and elimi-nation result in overall substitution.

Scheme 2.1

The hybridization state of the carbon atom that is attacked changesfrom sp2 to sp3and the planar aromatic system is destroyed. An unstableis simultaneously produced and so it is clear that this step isenergetically unfavourable. It is therefore the slower step of the sequence.However, the intermediate carbocation is stabilized by resonance, withthe positive charge shared formally by three carbon atoms of the ben-zene ring (Scheme 2.2). The resonance hybrid structure 1 indicates thedelocalization of the charge. The carbocation is also referred to as aor

In the second step, a proton is abstracted by a basic species presentin the reaction mixture. The attacked carbon atom reverts to sp2hybridization and planarity and aromaticity are restored. This fast stepis energetically favourable and is regarded as the driving force for theoverall process. The product is a substituted benzene derivative.The energy changes that occur during the course of the reaction arerelated to the structural changes in the reaction profile shown in Figure2.1. It should be noted that each step proceeds through a high-energytransition state in which partial bonds attach the electrophile and theproton to the ring and the n-cloud is incomplete.


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Aromatic Substitution 17

Figure 2.1 Energy profile for electrophilic attack on benzene

Most examples of electrophilic aromatic substitution proceed by thissequence of events:

Generation of an electrophileThe electrophile attacks the n-cloud of electrons of the aromatic ringThe resulting carbocation is stabilized by resonanceA proton is abstracted from the carbocation, regenerating theA substituted aromatic compound is formed~c-cloud

In the following sections, various examples are reviewed, highlightingthe source of the electrophile and any variations in mechanistic detail.Further discussion of the reactions and the products will be found inChapters 4-9, which deal with the chemistry of functionalized deriva-tives of benzene.

2.2.1 Nitration of BenzeneBenzene cannot be nitrated using nitric acid alone, which lacks a strongelectrophilic centre, but it is readily achieved using a mixture ofconcentrated nitric acid and concentrated sulfuric acid, the so-calledmixed acid. The product is nitrobenzene. The interaction of nitric acidand sulfuric acid produces the electrophile, the nitronium ion NO,+,according to Scheme 2.3. The sulfuric acid is also the source of the baseHSO, that removes the proton in the second step.


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Scheme 2.3

2.2.2 Halogenation of BenzeneHalogen molecules are not strong electrophiles and, fluorine excepted,do not react with benzene. However, in the presence of a Lewis acid,reaction occurs readily. The role of the catalyst is to accept a lone pairof electrons from the halogen molecule, which then becomes electrondeficient at one of the halogen atoms. The actual electrophile is proba-bly the complex formed from the halogen and the catalyst, rather thana halonium ion, e.g. Cl+ or Br+. Bromination of benzene serves as a goodexample of halogenation (Scheme 2.4).

Scheme 2.42.2.3 Friedel-Crafts AlkylationAlkyl halides require a Lewis acid catalyst to accentuate the polariza-tion and create a more powerful electrophile. There is not enough pos-itive character on the carbon atom in alkyl halides for them to react withbenzene; the catalyst increases the positive character. Aluminium

Scheme 2.5


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Aromatic Substitution 19chloride is commonly used as the Lewis acid, accepting a pair of elec-trons from the halogen atom (Scheme 2.5). The electrophile may be acarbocation or perhaps m ore likely the complex shown. An alkylbenzeneis produced.2.2.4 Friedel-Crafts AcylationAcylation can be achieved using either acyl halides or acid anhydrides.The product is a ketone. Acyl halides are more reactive than the anhy-drides, but still require a Lewis acid catalyst to promote the reaction(Scheme 2.6) . The attacking species is the resonance-stabilized acyliumion or the complex.

Scheme 2.6

2.2.5 Sulfonation of BenzeneBenzene itself is not attacked by concentrated sulfuric acid, but is read-ily conv erted t o b enzenesulfonic acid by fuming sulfuric acid. This is asolution of sulfur trioxide in concentrated sulfuric acid, and is know n asoleum. No te here tha t the attacking electrophile is a neutral species andthat the electron-deficient sulfur atom of SO, is the electrophilic centre(Scheme 2.7).

Scheme 2.7

Sulfonation differs from the other examples which hav e been discussedin tha t it can readily be reversed. Heating benzenesulfonic acid with dilutesulfuric acid or water converts it back to benzene.


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2.2.6 ProtonationAlthough benzene is a very weak base, it is protonated in concentratedsulfuric acid to a very slight extent. This reaction can be detected if theprotonating mixture contains deuterium or tritium, the isotopes ofhydrogen, since isotope exchange takes place. Some deuteriated benzeneis produced when benzene is treated with D,SO,, and this can be detect-ed by mass spectrometry and NMR spectroscopy. The more deuteriumthere is in the protonation mixture, the more exchange occurs. Noticethat the regeneration of the aromatic system occurs by elimination of aproton (Scheme 2.8).

Scheme 2.8

2.3 Reactivity and Orientation in ElectrophilicAromatic SubstitutionHow do derivatives of benzene behave towards electrophilic attack?Two experimental observations illustrate that the behaviour is quitevaried. The rate of nitration of toluene is appreciably faster than that ofbenzene and produces a mixture of 2- and 4-nitrotoluenes. On the otherhand, the nitration of nitrobenzene is more difficult than that of ben-zene and gives just one product, 1,3-dinitrobenzene (Scheme 2.9).


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A substituent in a benzene ring therefore influences the cou rse of elec- Scheme 2.9trophilic substitution in two ways:It affects the reactivity of the m oleculeIt controls the orientation of attack, i.e. which isomer is formed

It is important to understand why this should happen. In the aboveexamples, the two substituents, the methyl group and the nitro g roup,exhibit different electronic behaviour. The methyl group is anand so increases the electron density of the ring. Th e nitro gro upis anIt is these properties that influence the course of the reactions ofaromatic compounds with electrophiles. An electron-releasing groupincreases the electron density of the benzene ring, p rom oting electrophilicattack. Such substituents are known as . An electron-withdrawing gro up is an d reduces the electron density ofthe ring, m aking attack by the electron-deficient reagent m ore d ifficult.Both types of substituents affect the electron density at all positionsof the ring, bu t exert their greatest effects at the ortho and para positions,making these sites the mo st electron rich in the case of don or groups andmost electron deficient when electron-withdrawing groups are present.D on or gro ups therefore direct attack o f the electrophile to theortho andpara positions and are known as . Conversely, aro-matic compounds containing electron acceptor groups are attacked atth e meta position since this is the least electron-deficient site. Such grou psare called .N ot all substituents fit exactly into this picture:halogens are deactivating but direct attack to the ortho and para posi-tions.

and withdraws electron density from the ring.

Electron-donating substituents activate the benzene ring to electro-philic attack, which results in the formation of th e ortho- and para-disubstituted benzene derivatives.Electron-withdrawing substituents deactivate the ring to attack byelectrophiles, which o ccurs at th e meta position.Substituents exert their influence on a molecule through either the 0-bonds or the .Jc-bonding system, in other words by inductive andmesomeric (resonance) effects, respectively (see below). The interaction


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22 Aromatic Chemistryinfluences bo th th e electron d ensity at the various ring positions an d thestability of the intermediate carbocation. The outcome can be under-stood by superimposing the electronic effects of the substituents on theslow, rate-determining step of the general mechanism for electrophilicaromatic substitution discussed above.

In a o-bond between two atoms of differing electronegativities thereis an unequal sharing of the electron pair, with the electrons being attract-ed towards the more electronegative atom. This causes a permanentpolarization of the m olecule. This influence of an atom or g roup on thedistribution of the electron pair is called the . Inductiveeffects rapidly die away along a saturated carbon chain (see 4).Substituents in an aromatic ring that withdraw electrons in this wayexert a . They include not only halogens and the hydroxyl andnitro groups, where an electronegative atom is attached to the ring, butalso groups such as carbonyl and nitrile in which an electron-deficientcarbon atom is bonded to the ring. Alkyl groups behave in the oppositemanner, exerting a is the analogous redistribution of electrons inn-bonds. However, this resonance effect is transmitted throughout thewhole of a conjugated system and creates alternate polarity at the car-bon atoms along the system. Substituents that withdraw electron densi-ty in this way ( ) include carbonyl (see 5 ) and nitro groups,whilst electron-releasing ( ) functions include amino and hydroxygroups.Note that some groups can withdraw electrons by one of the twoeffects but release electrons by the o ther, altho ugh one o f the effects usu-ally predominates.

6 6 + & 6c-c-c-c-c14

and releasing electron density to the ring.The

2.3.1 Groups which Donate Electrons by the MesomericEffect

Groups (Z) in which the atom attached to the benzene ring possesses alone pair of electrons can interact with the aromatic ring as shown in 6 ,promoting ortho and para attack. The ring becomes more electron richand so the reaction w ith electrophiles is facilitated. Y ou can think of thelone pair of electrons as being formally located at the ortho and parapositions.In order to assess the influence that substituents have on the reactiv-ity of aromatic molecules, it is important to consider their effects notonly on the benzene ring itself as above, but also on the carbocationintermediates resulting from electrophilic attack. These species are rela-tively unstable and any feature that affects their stability will influencetheir ease of formation and therefore the outcome of a reaction.We can illustrate the latter point by examining the attack by an elec-


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Aromatic Substitution 23trophile E" on methoxybenzene (anisole) at the three possible sites ofattack (Scheme 2.10).

Consider first attack at the ortho position. The structure 7 has thepositive charge located on the carbon atom to which the methoxy groupis bonded. Notice that this is a , a species that isrecognized as being particularly stable (remember nucleophilic aliphaticsubstitution reactions). An additional canonical structure can be drawninvolving donation of the lone pair of electrons on the oxygen atom tothe electron-deficient C'. This fourth canonical form confers extrastability on the intermediate and lowers the energy of the transition stateleading to it. An oxonium species such as 8 is more stable than acarbocation, e.g. 7,and hence can be considered to contribute more tothe resonance hybrid.

A similar situation arises with species 9 associated with attack at the4-position and this carbocation intermediate is therefore also addition-ally stabilized by 10. However, no such structure can be drawn follow-ing meta attack and so the cation derived from this mode of attack isnot additionally stabilized.

The consequences of the involvement of the methoxy group are tostabilize especially the carbocations arising from ortho and para attackand to lower the energy of activation for their formation, as illustratedin Figure 2.2. Notice that even attack at the meta position has a loweractivation energy than does benzene.

Scheme 2.10


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Figure 2.2 Energy profile forelectrophilic attack on methoxy-benzene at the ortho,meta andpara positions compared withbenzene

It should therefore be no surprise that the nitration of methoxyben-zene is easier and faster than that of benzene and yields essentially onlythe 1,2- and 1,4-isomers (in almost equal amounts). Less than 1% of 3-nitroanisole is formed. Other electrophilic reactions follow this pattern.

and groups behave like a methoxy group. 9in which the oxygen carries a full negative charge, are especially acti-vated towards electrophilic attack.

atoms also fall into this category. Possessing a lone pair ofelectrons, they are able to stabilize the intermediate cation arising fromortholpara attack. However, the halogenobenzenes behave differentlyfrom methoxybenzene and aniline in that the reaction with electrophilesis slower than for benzene. The nitration of chlorobenzene is about 30times slower than that of benzene. Halogens are deactivating substituentsand yet are ortholpara directors. As with methoxy and amino groups,the halogens withdraw electrons inductively, but donate them by themesomeric effect. Only in the case of the halogens does the former effectdominate, with the consequence that the three intermediates from ortho,meta andpara attack are all less stable than that arising from electrophilicattack of benzene. Nonetheless, ortholpara attack is still favoured becauseof the additional stabilization of the cations from the resonance forms

& 0H E

11 12 11 and 12.2.3.2 Groups which Withdraw Electrons by theMesomeric EffectSubstituents which fall into this category includeand . All are characterized by the atom attached to the ring beinglinked to a more electronegative atom by a multiple bond and may berepresented by X=Y, where Y is more electronegative than X (see Scheme


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Aromatic Substitution 252.11). Electrons are therefore attracted towards Y, making X moreelectron deficient and therefore more strongly electron withdrawing.Formally, a positive charge is placed on the ortho and para positions.

Electrophilic attack on compounds which contain a substituent thatwithdraws electrons from the ring always leads to the 3-substituted com-pound, with very little of the 2- and 4-isomers being formed. The reac-tion is more difficult than for benzene, in keeping with the reducedelectron density at the ring carbon atoms.Again, it is important to examine the intermediates formed by attackof an electrophile, E+, at the ortho, meta and para positions (Scheme2.12). This time, nitrobenzene will be used as the substrate. It should benoticed that in the structures 13 and 14 associated with ortho and paraattack, a positive charge is placed on the carbon to which the substituentis attached. The resulting situation is destabilizing because positivecharges are located on adjacent atoms.

Scheme 2.1I

Scheme 2.12


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I 0 0 OR NII II I 111 o*+/o-C < < O=S=O < C < NAr' 'OR ArR I I I

Figure 2.3 Energy profile forelectrophilic attack on nitroben-zene at the ortho,meta and parapositions compared with benzene

Figure 2.4

While attack at the 3-position is still much slower than for benzene,no canonical form places positive charges on adjacent atoms and so theintermediate is less destabilized than those arising from ortho and paraattack. Hence meta attack is the preferred reaction, as illustrated inFigure 2.3. For example, nitration of nitrobenzene gives 88% of 1,3-dinitrobenzene and only 8% and 1% of the 1,2- and 1,4-isomers, respec-tively. The reaction occurs at a relative rate of 6 x lo-* to that of benzene.

The efficiency of electron withdrawal by substituents increases in theorder shown in Figure 2.4.

Ar Ar Ar


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Scheme 2.13

2.3.3 Groups which Withdraw Electrons by the InductiveEffectGroups such as ,CF,, and ,R,N+,areunable to interact with the n-system, but withdraw electrons as a resultof the electronegativity of the fluorine atom s an d the positively chargednitrogen, respectively. A study of the canonical forms for electrophilicattack at the three sites indicates a situation similar to that discussedabove for mesomerically withdrawing groups (Scheme 2.14). The inter-mediates are overall destabilized by electron withdrawal, but structures15 and 16 are particularly unfavourable because the positive charge isadjacent to the electron-deficient atom of the substituent. Thus, attackoccurs preferentially at the 3-position, but is more difficult than elec-trophilic attack on benzene.2.3.4 Groups which Donate Electrons by the InductiveEffectIt is well know n tha t, in comparison to hydrogen, do nateelectrons. It is therefore to be expected that toluene and other alkylben-zenes will react with electrophiles rather more easily than benzene.This is certainly the case, toluene reacting with mixed acid at roomtemperature.The canonical forms that contribute to the structure of the inter-mediate carbocation are shown in Scheme 2.15. Once again, one con-


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Scheme 2.14

Scheme 2.15


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Aromatic Substitution 29tributing form derived from attack at the 2- and the 4-positions has thepositive charge located on the carbon atom to which the substituent isattached. I t is noted th at these structures, 17 and 18, are tertiary carbo-cations an d th at they are furthe r stabilized by delocalization of the chargeonto the methyl group, which therefore shares some of the electrondeficiency. N o such benefit results from attack at the 3-position, whichis therefore not a favoured site for reaction. Nitration of toluene occursabout 25 times faster than that of benzene under similar conditions. Itleads to a 2:l mixture of 2- and 4-nitrotoluenes; only about 5% of theproduct is the 3-isomer (rememb er there are two ortho positions but onlyone para position).Th e m ore efficient the a lkyl group is at releasing electrons, the greateris the stabilization of the intermediate carboca tion and the rate of elec-trophilic attack. Thu s, tert-butylbenzene is nitrated faster than toluene.This picture is som ewhat generalized, since there are some exceptions.For instance, the chlorination of toluene proceeds faster than that oftert-but ylbenzene. (Scheme 2.16) is at a maximumfor a methyl group and has been offered as an explanation for theseanomalies.

Scheme 2.16


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2.3.5 The Effects of Multiple SubstitutionIn general, the effects of two substituents on the orientation and rate ofelectrophilic substitution are additive. The best product selectivity occurswhen the two substituents are working together, but unfortunately thisis not always the case.There are several guiding principles that help to decide the product inless obvious cases:

Strongly activating groups dominate all other substituentsWeakly activating groups next take control of orientationDeactivating groups exert the least controlSteric effects often play a part in deciding the outcome of a reaction

When devising a synthesis of a particular compound (the target mole-cule), the effects of substituents have to be taken into account. It is essen-tial to introduce substituents in the correct order so that their directinginfluence assists the synthesis rather than hinder it. Remember:

ortho/para directors give mixtures of two isomers that can usually beseparatedmeta directors give only the meta isomerortho/para directing groups always overcome the influence of metadirectorsattacka strongly electron-withdrawing groups may prevent electrophilic1

Aromatic hydrocarbons such as naphthalene (19) also undergo elec-trophilic substitution, although now not all ring positions of the parenthydrocarbon are equivalent. Nitration occurs almost exclusively in the1- or a-position of naphthalene. Consideration of the contributing struc-tures to the hybrid carbocation indicates why this is so. For a-attack,the canonical structures include 20,21 and 22.Whereas in 20 and 21 thestable aromatic sextet is preserved, in 22 the aromaticity is disrupted.However, for attack at the 2- or P-position, only one structure, 23, can

a2p19


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Aromatic Substitution 31be drawn in which the aromatic sextet is preserved. It is therefore expect-ed that the carbocation produced during a-attack is more stable thanthat formed from P-attack and hence the rate of reaction at the a-posi-tion is significantly faster.

The effects of substituents on the regioselectivity of electrophilic aro-matic substitution are summarized in Table 2.1.

Table 2.1 Reactivity and directing effects of substituent groupsortho/para directors meta directorsStrongly activating groupsNR,, NHR, NH,, NHCOCH,0-, OH, ORWeakly activating groupsAlkyl phenylWeakly deactivating groupsF, CI, Br, I

Strongly deactivating groupsNO,, 'NR,SO,H,CO,H, CO,R, CORCN, CF,

2.4 The Hammett EquationThe relative ability of substituents in an aromatic ring to donate or with-draw electrons is indicated qualitatively by. It was observed that a plot of the logarithms of the rate constants( k ) for the alkaline hydrolysis of esters of benzoic acid against the PKavalues of the corresponding acids, XC,H,CO,H, was linear, i.e .

where p (rho) and C are constants.


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32 Aromatic ChemistryThe line

describes the point for the unsubstituted compounds (X = 13).Subtraction of equation (2.2) from equation (2.1) gives:

Log k and PKa are related to free energies of activation and ionization,respectively, and hence a linear free energy relationship exists betweenthe rates of ester hydrolysis and acid strengths.

Similar correlations between rate and equilibrium constants exist forvarious other side-chain reactions of benzene derivatives. The magnitudeof p, which is called the , is the slope of the line andvaries with the reaction. The sign of p can be positive or negative accord-ing to whether the reaction rate is increased or decreased by the with-drawal of electrons.

The term (PKaO - PKa) is given the symbol o sigma) and is constantfor given substituents. Equation 2.3 thus simplifies to:

log klko = po (2.4)This is the

The data for the ionization of benzoic acid and its derivatives in waterat 25 "C are extensive and accurate and this was chosen as the standardreaction to which all other reactions would be compared. The value ofp for the standard reaction is 1.00. , o, s a measure of the electron-donating or electron-withdrawing power of the particular substituent,with H being given a value of 0.00. Some typical values are listed inTable 2.2. These linear free energy correlations only apply to meta andpara substituents in aromatic systems, sinceortho substituents exert steric

The

Table 2.2 Hammett substituent constants for some substituentsSubstituen Ometa Omra Substituen Ometa Omra0- -0.71 -1.00 F +0.34 +0.06NH2 -0.16 -0.66 CI +0.37 +0.23OH +0.12 -0.37 COCH3 +0.38 +0.50CH3 -0.07 -0.17 CF3 +0.43 +0.54OCH3 +0.11 -0.27 CN +0.56 +0.66

' H 0.00 0.00 NO2 +0.71 +0.78


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Aromatic Substitution 33effects which can alter the normal electronic behaviour. It can be seenthat the more negative the value, the higher the electron-donating capac-ity of the group; substituents with a positive B value are electron with-drawing.The B values reflect the interaction of the substituents with the reac-tion centre. The methoxy group can exert only its -I effect in the metaposition: the stronger + M effect dominates in the para position.Consequently, Ometa and opara have opposite signs for this group,indicating its electron-withdrawing and electron-donating ability,respectively.2.5 Nucleophilic Aromatic SubstitutionThere are two distinct and major mechanisms by which acan be introduced into the aromatic ring. In one, the nucleophiat a ring carbon atom and this type is covered in detail belowond method depends on an electron-rich species behaving as aattacking at hydrogen. This type of reaction is covered inChapter 9 and is only briefly considered here.

e attacksThe sec-base anddetail in

2.5.1 By an Addition-Elimination Mechanism (S,Ar)Whereas electrophilic attack of benzene is both well known and impor-tant, the corresponding reaction with nucleophiles is very difficult andis not typical of aromatic compounds. However, if the aromatic ring isIT-electron deficient because an electron-withdrawing group (EWG) ispresent, then nucleophilic attack can occur. The mechanism for the addi-tion-elimination sequence for nucleophilic substitution is shown inScheme 2.17.

The initial attack disrupts the IT-cloud and the resulting intermediatespecies, a carbanion, is stabilized by resonance. There is a close similaritybetween this mechanism and that proposed earlier in this chapter forelectrophilic attack on benzene, although in that reaction the inter-mediate was a carbocation. In both cases, this first step is usually theslower and therefore rate determining.Evidence to support this mechanism for nucleophilic substitution

Scheme 2.17


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Scheme 2.18

and displaces the halide ion in an intramolecular process. The initialproduct is a highly reactive species called an aryne. It is rapidly attackedby NH, , or its protonated derivative NH,, now acting as a nucleophile.The final product, which results from protonation of a second carban-ion, is the new substituted benzene derivative (Scheme 2.19).

Scheme 2.19

2.6 ips0 SubstitutionElectrophilic attack can also occur at a position already occupied by asubstituent, the @so position. Such ips0 substitutions are not common,but they are industrially useful. An example is @so nitration by

OH OHH03s7($Meq.H N 0 3lS04 02N@MeM e M eI IMe Me

Scheme 2.20


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36 Aromatic Chemistrydisplacement of a sulfonic acid gro up (Scheme 2.20). A proton can alsodisplace the sulfonic acid group, with benzenesulfonic acid being con-verted into benzene. Nucleophilic ips0 substitution reactions also occur(see Section 2.5.1).


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M e

1M e

bMe2 o-xylene(1,2-dirnethylbenzene)4. e3 rn-xylene( I ,3-dimethylbenzene)

M e4 p-xylene(1,4-dirnethylbenzene)

Alkylbenzenes andArylbenzenes

3.1 IntroductionBenzene and its simple alkyl derivatives are the building blocks of thearomatic chemical industry and are also important solvents for manyreactions and processes. The simplest derivative, (methyl benzene,l) , s the source of a range of nitrotoluenes and is one of the most impor-tant industrial solvents. The three isomeric dimethylbenzenes, u- , m- andp-xylene (2-4) are often used as a mixture in industrial solvents.3.2 Sources of AlkylbenzenesTraditionally, the source of benzene and toluene has been coal. Coke isproduced for use in the steel industry and a by-product of this processis coal tar which, when distilled, provides benzene, toluene, xylenes, phe-nol and cresols (methylphenols), and naphthalene, the most abundantsingle component.However, the major source of these hydrocarbons is now petroleum.Although aromatic compounds do occur naturally in petroleum, they aremainly obtained by the process of catalytic reforming, in which aliphat-ic hydrocarbons are aromatized through dehydrogenation, cyclizationand isomerization. The process, which is also known as ,is carried out under pressure at 480-550 "C in the presence of a catalyst,typically chromium(II1) oxide or alumina. Benzene is thus produced from


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Alkylbenzenes and Arylbenzenes 39hexane, an d toluene fr om h eptane. O ctan e gives rise to the three isomersof xylene and to ethylbenzene. Since more toluene than benzene is pro-duced in the process, a qu antity of toluene is converted in to benzene by. High temperature (650-680 " C ) of longerchain alkanes, a process that breaks them down into smaller alkanes, isalso a source of aromatic compounds.3.3 Introduction of Alkyl Groups3.3.I Friedel-Crafts ReactionThe most important means of introducing an alkyl group into anarom atic ring is the . In its simplest form, this isthe reaction of an alkyl halide (halogenoalkane) with an aromaticcompound, such as benzene, in the presence of a , commonlyaluminium chloride (Scheme 3.1).

L -1 cheme 3.1A wide range of reactants, catalysts, solvents and rea ction conditionscan be used, ma king the Friedel-Crafts reaction a very valuable an d ver-

satile process.As well as alkyl halides, alcohols and alkenes are direct sources ofalkyl groups. Acyl chlorides and anhydrides are additional sources, butthese involve the subsequent reduction of a carbonyl group (C=O) to amethylene (CH,) unit.A variety of cata lysts, including o ther Lewis acids such as FeCl, and

BF,, and the protic acids HF, phosphoric acid and sulfuric acid, has beenused. In reactions using alcohols, the favoured catalyst is BF,; HF isoften used in reactions involving alkenes.The reaction can be very fast, but can be moderated by the use of a ninert solvent such as nitrobenzene or carbon disulfide. The temperatureat which the reaction is carried out can vary from below room temper-a ture to a bout 200 "C .However, there ar e several drawbacks to this alkylation rea ction. Theuse of longer alkyl chains than ethyl can be complicated by isomerizationof the alkyl grou p arising from carbo nium ion hydride shifts. It is there-fore not uncommon for mixtures to be produced. In extreme cases, acompletely different alkyl group from that of the starting material canbe present in the product.

A specific examp le is the alkylation of benzene with 1-chloropropane


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40 Aromatic Chemistryin the presence of aluminium chloride. Propylbenzene ( 5 ) predominateswhen the reaction mixture is kept cold, but as the temperature isincreased, isopropylbenze ne (6) becomes the major prod uct an d a t 80 "Caccounts for approximately 70%0of the mixture.Reaction conditions ca n also influence the orientation of substitution.An exam ple is the reaction of toluene with ch loro me than e in the presenceof aluminium chloride. At room temperature, a mixture of 1,2- and1,4-dimethylbenzenes results, but at 80 "C the product is mainly1,3-dimethylbenzene. In fact, heating eithe r of the 1,2- o r 1,4-isomersin the presence of aluminium chloridelhydrochloric acid results inrearrangement to the more stable 1,3-dirnethylbenzene.

A further drawback results from the electron-donating nature ofalkyl groups, which assists attack on the benzene ring by electrophiles.Th e initial pro duc t, an alkylbenzene, is therefore mor e reactive tha n thestarting material and a second and even further alkylation may occur,leading to mixed products.Isomerization does not occur in the route that involves acylation andcarbonyl red uction. This technique also prevents polysubstitution, sincethe acyl gr ou p is electron withdrawing an d deactivates the ring to fur therelec rophilic attack .Friedel-Crafts alkylation fails when the sub strate con tains morepowerful electron-withdrawing groups than halogen. Nitrobenzene istherefore a useful solvent for the reaction. Aromatic amines, althoughreactive towards electrophilic attack (see Chapter 8), d o not undergoalkylation. The lone pair of electrons on the N atom of the amino groupforms a coordinate bond to the AlCl,, preventing its complexation tothe alkyl halide. It should also be noted th at the reaction does not w orkwith aryl halides.

5 6

3.3.2 Mechanism of the Friedel-Crafts ReactionIn reactions involving alkyl halides, two mechanisms have beenrecognized w hich differ in the exact na tur e of the electrophile. O ne mech-anism involves an generated by abs trac tion of the halo-gen from the alkyl halide by the AlCl,. In the second processl;a complexform ed between the halide an d the Lewis acid such as [R-Cl-AlCl,] isthe attacking electrophile. The difference between the two mechanismsis essentially whether an alkyl cation is actually formed (Scheme 3.2) andthe effective mechanistic pathway may be somewhere between the two.In the first mechanism, th e reaction involves attac k of th e cation o n thebenzene ring followed by abstraction of a proton by [AlCl,]-, which isformally converted into HC1 and AlCl,.In the second mechanism, the alkyl group is transferred to the aro-matic ring from the complex.


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Alkylbenzenes and Arylbenzenes 41

Scheme 3.2

Alcohols and alkenes generate these carbocations in the presence ofacids such as sulfuric acid (Scheme 3.3). Some alkyl cations re arrange toform the most stable ion, thus accounting for the isomerization notedearlier.

Scheme 3.3

In the case of acyl chlorides, reaction with the Lewis acid generatesan electrophilic . These species show no tendenc y to re arrange(Scheme 3.4). Again, it is questionable whether a free cation is formedor if a complex between the acyl grou p an d A lCl, is the attacking species.

Scheme 3.43.3.3 Wurtz-Fi tt g React onAlkyl derivatives of benzene ma y be prepa red by reacting an alkyl halideand an aryl halide with sodium in an inert solvent such as diethyl ether(Scheme 3.5). Although symmetrical by-products are also formed, it ispossible to introduce long unbranched side-chains by this route withoutisomerization occurring.

Scheme 3.5


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42 Aromatic Chemistry3.4 Reactions of Alkylbenzenes3.4.1 Reactions of the RingAn alkyl group activates the ring to electrophilic substitution mainlythrough an inductive effect and directs attack t o the 2- an d 4-positions.Examples of these reactions will app ear thro ugh out the bo ok in the chap-ters o n functionalized a rom atic compounds.3.4.2 Reactions of the Side-chainFree Radical HalogenationIn the presence of light, but in the absence of a Lewis acid catalyst,halogenation of toluene occurs in the methyl group by a free-radicalmechanism. The reaction proceeds stepwise, leading eventually to(trichloromethy1)benzene (benzotrichloride, PhCCl,). With ethylbenzene,a similar reaction results; chlorination occurs initially a t the a-p osition .

c1

8


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Alkylbenzenes and Arylbenzenes 43

Scheme 3.6

Side-chain OxidationOxidation of aromatic systems containing alkyl side-chains results in theformation of a carboxylic acid, irrespective of the length of the side-chain. The usual oxidizing agents are potassium permanganate [potassi-um manganate(VII)] or chromic acid [chromium(VI) acid]. For example,1,4-dirnethylbenzene is oxidized to benzene- 1,4-dicarboxylic acid (tereph-thalic acid, 9), an important building block for polyesters. The oxida-tion of isopropylbenzene (cumene) to phenol is an important industrialprocess and is discussed in Chapter 4.Side-chain DehydrogenationStyrene (phenylethene, 10) is an important industrial chemical, that isprepared by dehydrogenation of ethylbenzene at 600 "C over zinc oxideor chromium(II1) oxide on alumina (Scheme 3 .7 ) . Ethylbenzene can beproduced from benzene and ethene by a Friedel-Crafts reaction.

0 3P04 -00C 0"/ H*C=CH;? / catalyst /

C02HI

C02H9

10Scheme 3.7


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Scheme 3.8

3.5 Aryl Derivatives of BenzeneThere are two classes of compounds that can be considered to fallinto this category. The simplest such derivative is ( l l) , n whichtwo benzene rings are connected via a carbon-carbon single bond. Thiscompound can be prepared by from bromobenzene orby the from benzenediazonium sulfate in the presenceof ethanol and copper (Scheme 3.9), although yields are poor. Biphenylsmay also be prepared using organometallic coupling (see Chapter 10).

Br 2N aFittig___t

CuEtOHGombergPScheme 3.9

Biphenyl undergoes typical electrophilic substitution reactions. Thephenyl group is ortholpara directing. For example, the major product ofmononitration is 4-nitrobiphenyl. Introduction of a second nitro groupin the molecule occurs in the unsubstituted ring, also, mainly, in the 4'-position. This might be unexpected since a nitrophenyl group is electronwithdrawing, and therefore meta directing. However, irrespective of theelectronic properties of the mono substituent, electrophilic substitutionof a second substituent generally occurs in the 4'-position of the unsub-stituted ring. The positive charge associated with the carbocation inter-mediate from para substitution can be delocalized into the second phenylring and so is efficiently stabilized. This is not the case with the Whelandintermediate from meta attack, which is therefore not the preferred siteof substitution. You should draw these two possible intermediate cationsand their resonance structures to confirm this.


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Phenols

4.1 IntroductionPhenol (hydroxybenzene, 1) has a hydroxyl group attached directly tothe benzene ring. Phenol is a stable enol and, although there are someobvious similarities, the hydroxyl group exhibits sufficiently differentproperties from an alcoholic hydroxyl group to merit a separateclassification.4.2 Industrial Synthetic MethodsAlthough coal tar is still an industrial source of phenol and the threecresols (methylphenols), e.g. m-cresol (2), and the dimethyl derivatives(xylenols), synthetically manufactured material predominates.Most phenol nowadays is obtained from isopropylbenzene (cumene),which is oxidized by air in the (Scheme 4.1). Acetone(propanone) is a valuable by-product of the process and this route is amajor source of this important solvent. The formation of cumenehydroperoxide proceeds by a free radical chain reaction initiated by theready generation of the tertiary benzylic cumyl radical, which is a fur-ther illustration of the ease of attack at the benzylic position, especiallyby radicals (see Chapter 3) .

47


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48 Aromatic ChemistryThe mechanism is considered to proceed as shown in Scheme 4.1.Protonation of the cumene hydroperoxide results in loss of water, gen-erating an electron-deficient oxygen atom. A 1,2-shift of the phenyl groupoccurs, probably simultaneously. Finally, the protonated hemiketal 3 ishydrolysed under the acidic conditions to produce phenol and acetone.

(seep. 108), is resistant to nucleophilic substitution under normal conditions,but in the , reatment with sodium hydroxide at 300 "C underhigh pressure is effective. Phenol may also be prepared from chloroben-zene by reaction with steam at 450 "C over a catalyst.

Chlorobenzene, commercially produced by the

Scheme 4.14.3 Laboratory SynthesesThe hydroxyl group cannot be directly substituted into the aromatic ring,but is introduced through conversion of other substituents.4.3.1 From Arenesulfonic Acids

S03H OHI I

Scheme 4.2

The fusion of alkali metal sulfonates with alkali in the presence of somewater is used both in the laboratory and in industry (Scheme 4.2).4.3.2 From Aryl HalidesThere are two useful ways by which halogen can be displaced by ahydroxyl group. As discussed in Chapters 2 and 9, only aryl halides thatare activated by electron-withdrawing groups are susceptible to nucle-ophilic substitution, when even water and aqueous sodium hydroxidecan be effective reagents. A hydroxyl group can also be introduced byconversion of the aryl halide into a Grignard reagent or an aryllithiumcompound and subsequent reaction with oxygen or through the inter-mediacy of the boronic acid (see Chapter 10).


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Phenols 49

4.3.3 From Amino CompoundsThe amine is converted into a diazonium salt which is then warmed withwater (see Chapter 8).4.3.4 Miscellaneous MethodsThere are a number of less frequently used methods for the preparationof phenols that are worthy of mention. The rearrangement of 2-hydroxy-benzaldehydes brought about by reaction with alkaline hydrogen per-oxide and leading to dihydroxybenzenes (the ) is discussedin Section 4.8. The acid-catalysed rearrangement of phenylhydroxy-lamines, known as the , is useful for the syn-thesis of 4-aminophenols (Scheme 4.3).

Scheme 4.3

Scheme 4.4


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Scheme 4.5

4.4 The Acidity of PhenolsPhenols are converted into salts with strong alkalis such as sodiumhydroxide, but not with sodium hydrogen carbonate solution. They aretherefore stronger acids than alcohols but weaker than carboxylic acids.The pKaof phenol is 9.95 compared with 4.20 for benzoic acid and about17 for cyclohexanol.The acidity of phenols arises from the greater resonance stabilizationof the phenoxide anion compared with phenol itself (Scheme 4.6). Thereis no energy-demanding separation of charge in the resonance structures

Scheme 4.6


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Phenols 51for the anion (7-9) as there is for phenol (4-6). Thus, the equilibriumbetween phenol and its anion is displaced towards the latter species, witha correspo nding increase in acidity.The influence of ring su bstituents on the acidity of th e phenolic grou pis depend ent o n the electronic properties of the sub stituent and its posi-tion in the ring relative to the hydroxyl group, Consider first the threemononitrophenols. In all cases, the electron-withdrawing inductive effect( - I ) of the nitro group will cause an increase in acidity. However, thenitro group can also interact mesomerically with the hydroxyl groupwhen it is in the 2- and 4-positions. The increased stabilization arisingfrom the -M effect, illustrated by the contributing structure 10, has amarked effect on the acidity. Thus , both 2- and 4-nitrophenols (pK, 7.23and 7.15, respectively) are ap proxim ately 1000 times stronger acids th anphenol. They are more than 10 times stronger than 3-nitrophenol (pKa8.40) in which the -M effect cannot operate.On the other hand, a methyl group exerts a weak + I effect and thusthe methylphenols are slightly less acidic than phenol (e.g. 4-methylphe-nol, pK;, 10.14).4.5 Reactions of the Hydroxy Group4.5.1 Ester Formation and Fries RearrangementWhen treated with acid chlorides and acid anhydrides, phenols formesters. Un der Friedel-Crafts con dition s, pheno lic esters und ergo ain which the acyl group migrates to the 2- and 4-posi-tions. Thus, treatment of the ester 11 with aluminium chloride in an inertsolvent gives a mixture of 2- and 4-hydroxyacetophenones [(hydroxy-pheny1)ethanonesl; C-acylation has occurred (Scheme 4.7). The two iso-mers are separable and this is a useful method for the production ofphenolic ketones. The mechanism remains uncertain, but it would app earth at the acylium ion (RCO+) s generated and tha t a Friedel-Crafts mech-anism operates.

OH OCOMe OH OH

11 ICOMeScheme 4.7


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4.5.2 Ether FormationWhen the sodium salt of a phenol is treated with an alkyl halide or analkyl sulfate, 0-a lkylatio n occurs an d an ether is formed , usually in go odyield. Methyl ethers such a s anisole (methoxybenzene) can also be form edin excellent yield by treatment of a phenol with diazomethane (Scheme4.8).

OH O-Na' OMeI I I

Scheme 4.8

A reaction peculiar to allyl aryl ethers is their rearrangement toallylphenols when heated. In this , he allyl grou pmigrates to the 2-position. It is an example of a an dproceeds through a cyclic, six-membered transition state (Scheme 4.9).The reaction has been investigated by labelling the y-carbon a to m withthe isotope 14C, marked with an asterisk in the scheme. The remotelabelled carbon atom in the original allylphenol becomes the a-carbonattached to the ring in the product. If both ortho positions are occupied,then migration to the para position occurs in two stages and the labeloccupies the y-position as in the starting material.

Scheme 4.9


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Phenols 53

Scheme 4.10

Scheme 4.1 1

4.6 Reactions of the Ring4.6.1 Electrophilic SubstitutionPhenols are highly activated towards electrophilic attack, which occursreadily at the 2- and 4-positions. For example, phenol reacts withbromine at room temperature in ethanol and in the absence of a cata-lyst to give 2,4,6-tribromophenol. Other electrophilic substitution reac-tions such as nitration, sulfonation, Friedel-Crafts, chlorination andnitrosation also proceed readily and hence care is needed to ensure multi-substitution does not occur. Protection of specific ring positions can alsoprevent unwanted substitution. Relatively mild conditions are usuallyemployed.


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4.6.2 Reactions of the Phenoxide IonUnder alkaline conditions, the phenoxide ion is formed, which is evenmore nucleophilic than phenol and hence more reactive. A number ofC-C bond-forming reactions take place under these conditions.An imp ortan t reaction of ph enols is the attack by weakly electrophilicarenediazon ium salts in aqueo us alkaline solution a t below 5 "C to formazo dyes. This coupling reaction is discussed in Chapter 8.The Reimer-Tiemann ReactionTreatment of a phenol with chloroform (trichloromethane) in the pres-ence of hydroxide ion results in the synthesis of a 2-hydroxybenzalde-hyde through C-formylation. Dichlorocarbene, :CCl,, is generated by theaction of base on chloroform and this highly reactive electrophile thenattacks the phenoxide. The m echanism of th eis given in Scheme 4.12.

Scheme 4.12

The Kolbe-Schmidt ReactionThe phenoxide ion is sufficiently nucleophilic to be attacked by carbondioxide, providing a useful method for the introduction of a carboxylicacid group; ortho carboxylation takes place at 120-140 "C. The prod uctof the on phenol is 2-hydroxybenzoic acid (sal-icylic acid) (Scheme 4.13).

Scheme 4.13


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Phenols 55

With FormaldehydeIn aqueous alkaline solution, phenol reacts with formaldehyde(meth anal) at low temperatures to fo rm a mixture of 2- an d 4-hydroxy-benzyl alcohols. This is an oth er example ofelectrophilic attack which results in the formation of a new C-C bond.The mechanism is illustrated in Scheme 4.14. These products readily losewater to form quinomethanes (methylenecyclohexadienones), whichreact with m ore phenox ide. This process is repeated over and over againto produce a cross-linked polymer or phenol-formaldehyde resin (e.g.Bakelite) in which th e aro ma tic rings ar e linked t o methylene bridges.

Reaction of 2,4,5-trichlorophenol (the antiseptic TCP) with HCHOyields hexachlorophene, a widely used germicide.

4.7 Dihydroxybenzenes Scheme 4.14Th e dihydroxybenzenes o r dihydric phenols 15-17 have trivial names asshown. OHIOH

&OH

OHc i H O H15 1,2-Dihydroxybenzene 16 1,3-Dihydroxybenzene 17 1,4-Dihydroxybenzene

(catechol) (resorcinol) (hydroquinone)1,2-Dihydroxybenzene may be prepared from 2-hydroxybenzaldehyde

by the which involves oxidation in alkaline solution byhydrogen peroxide (Scheme 4.15). The reaction involves a 1,2-shift to anelectron-deficient oxygen and is similar to the cumene process used tosynthesize phenol (Section 4.2).1,3-Dihydroxybenzene is prepared industrially by the alkali fusion ofbenzene- 1,3-disulfonic acid. 1,4-Dihydroxyben zene is prepare d in largequantities fo r use as a pho togr aph ic developer, one process being by theoxidation of aniline with manganese dioxide [manganese(IV) oxide] insulfuric acid to give benzo-1,4-quinone, which is then reduced to 1,4-dihydroxybenzene (hydroquinone, quinol).


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Scheme 4.15


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Phenols 57


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Aromatic Acids

5.1 IntroductionBoth the sulfonic acid ( -S0 ,H) and the carboxylic acid (-C0,H) groupsare encountered in aromatic molecules. Introduction of one sulfonic acidgroup into the benzene ring gives ( l) ,derivatives ofwhich are named as the substituted benzenesulfonic acid. The corre-sponding carboxylic acid is (2)5.2 Introduction of Acidic GroupsThe methods of introducing the two groups are quite different. Sulfonic acidsare usually obtained by direct electrophilic substitution, whilst carboxylicacids are produced through the conversion of another functional group.

5.2.1 Introduction of the Sulfonic Acid GroupBenzene reacts slowly with hot sulfuric acid to produce benzenesulfonicacid. The attacking electrophile, the cation 4, is generated by the self-protonation of sulfuric acid and reacts with the benzene ring in the nor-mal manner (Scheme 5.1).


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Aromatic Acids 59

Scheme 5.1

Dissolving sulfur trioxide, SO,, in sulfuric acid forms the same cationand these solutions, known as oleum or fuming sulfuric acid, readily sul-fonate benzene and even less reactive aromatic systems.There is some evidence from kinetic studies that the electron-deficientand therefore electrophilic sulfur trioxide is itself the attacking species,when the mechanistic pathway follows that illustrated in Scheme 5.2.

Chlorosulfonic acid also effects direct sulfonation, although whenused in excess the product is the sulfonyl chloride; subsequent hydroly-sis leads to the acid (Scheme 5.3).Scheme 5.2

S03H SO2Cl8 lS03H, 0 lSORH* 6 30+,Scheme 5.3

5.2.2 Introduction of the Carboxylic Acid GroupOxidative MethodsA variety of oxidizing agents, including potassium permanganate[potassium manganate(VII)], chromium trioxide [chromium(VI) oxide]in sulfuric acid, potassium dichromate and hydrogen peroxide, convertalcohols, aldehydes, alkyl and halogenated alkyl groups to carboxylicacids (Scheme 5.4). For instance, benzaldehyde is readily oxidized tobenzoic acid in good yield by potassium permanganate.


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Scheme 5.4

[OIArCH20H - rCHO[OI P I [OI

1 OIArCH2Cl - rCH20H - rC02H- rCH3Hydrolytic MethodsHydrolysis of acid chlorides, acid anhydrides, esters and carboxamidesleads to the carboxylic acid, although these compounds are often derivedfrom a carboxylic acid group in the first place (Scheme 5.5). Nitriles areusually derived from amines via diazotization and reaction with copper(1)cyanide (see Chapter 8) and so the hydrolysis of a nitrile group is of

more value. In all cases, alkaline hydrolysis gives the salt of the acid,from which the free acid is obtained by addition of mineral acid.

OH- 7 rCoC1ArCN- rC02Na ArCONH2 Br = CF3S03 > C1 > F.Reactions of iodides and bromides can often be carried out selectivelyin the presence of chloride and fluoride substituents.

Br, I ,PPh


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Organometallic Reactions 1211,2-insertion and proceeds via the intermediacy of a x-complex. The com-plex is best represented as a hybrid of the ncomplex and the metalla-cyclopropane (Scheme 10.15). Its true nature lies somewhere between thetwo extreme forms.

Scheme 10.15

Complexation to a metal activates a double bond towards the addi-tion of a nucleophilic species (Scheme 10.16). The metal has modifiedthe behaviour of the alkene, which would normally undergo additionreactions with electrophiles.

Scheme 10.16

I .4 Aryl Coupling Reactions10.4.1 The Ullmann CouplingSymmetrical biaryls can be formed by the coupling of two molecules ofan aryl halide in the presence of copper metal (Scheme 10.17).I I Scheme 10.17

This reaction is known as the , It is believed toinvolve the intermediacy of aryl copper complexes rather than radicalspecies. The reaction is best suited to the preparation of symmetricalbiaryls ("homo-coupled" products). Attempts to couple two differenthalides (Ar'X and Ar2X) in this way can lead to mixtures of the desiredcross-coupled product (Ar1-Ar2) and the two homo-coupled species(Ar I-Ar' and Ar2-Ar2).


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first to be developed extensively was the , which specifi-tally involves the coupling of an arylstannane with an aryl halide ortriflate under the action of palladium catalysis (Scheme 10.19).ArSnR3 + A ~ x Ar--Ar

10.4.2 The Stille and Related ReactionsThe synthesis of unsymmetrical biaryls 8 from two monoaryl speciesinvolves the coupling of a metallated aromatic molecule 6 with an arylhalide o r triflate 4 under the action of palladium(0) catalysis. The reac-tion involves a catalytic cycle in which palladium(0) inserts into theC-halogen bond viu an oxidative addition to generate anarylpalladium(I1) species 5 (Scheme 10.18). This undergoes a trans-metallation with the metallated component, producing a biarylpalladi-um(I1) com plex 7 . Th e biaryl product is formed by reductive elimination.In the process, Pd(0) is regenerated a nd this can then react with a secondmolecule of aryl halide. Pd(0) is therefore a catalyst for the reaction.

Scheme 10.18


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Organometallic Reactions 123

R A cheme 10.20(Scheme 10.21). It is quite common to use M to designate a metallicfunction. In Scheme 10.21, M represents tin and boron functions. Themechanism is analo gou s to tha t described previously.

The reactions may also be carried out under an atmosphere of car-bon m onoxide, CO (Scheme 10.22),when the usual catalytic cycle occurs.CO inserts easily int o the palladium com plex Ar-Pd'I-X. Th e arylligand migrates on to the carbonyl group to form a metal-acyl species,X-Pd"-C(0)A r. A transmetallation-reductive elimination sequence fol-lows, forming the ketone and regenerating the PdO catalyst.

Scheme 10.21

0 II- I Scheme 10.2210.4.3 The Heck ReactionThe direct coupling of an aryl halide with an alkene to produce aphenylethene is known as the (Scheme 10.23). The m ech-anism involves coord inatio n of the alkene to the palladium to for m a 7c-complex 9 with which the arene ligand can react. A variety of sub stituentson the alkene is compatible with the reaction.


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Scheme 10.23

10.4.4 Amination ReactionsAn aryl halide can also be coupled to an amine using metal catalysis.The reaction represents an alternative to the classical methods for thesynthesis of aryl amines, such as reduction of nitro groups and nucleo-philic aromatic substitution (see Chapter 8).The reaction is particularly useful for the synthesis of biaryl amines,some of which are of value as drugs, dyes and agrochemicals, and whichare often inaccessible directly by other methods.An amine can be coupled with an aryl bromide, iodide or triflate inthe presence of a palladium catalyst, a base, typically KOBu' or CsCO,,and a ligand such as the bidentate phosphine BINAP. These reactionsare known as or (Scheme 10.24).A catalytic cycle is again inyolved, with the amine displacing X fromAr-Pd"-X to form Ar-Pd"-NHR,. Abstraction of a proton by the baseproduces Ar-Pd"-NR,, which undergoes a reductive elimination.

Scheme 10.24


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Scheme 10.25

Scheme 10.26

10.5 Arene-Chromium Tricarbonyl ComplexesArenes form $-complexes with a num ber of transition m etals (e.g. Cr,M o, W, Fe). Complexes of chromium have found widespread applica-tion because of their ease of synthesis, stability, easy removal of theligands and usefulness in synthesis. hapticity number.10.5.1 Preparation and StructureThey may be prepared by heating Cr(CO), o r Cr(CO),(NH,), in thearene as solvent (Scheme 10.27) or, when use of excess aren e is undesir-able, by exchange with the naphthalene complex 10. The procedureworks well for electron-rich arenes, but is of no value for electron-deficient aromatic compounds. Decomplexation can subsequently be


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Scheme 10.2910.5.3 The Dotz ReactionA further application of chromium complexes in aromatic chemistryallows the construction of a new aromatic ring. In the

, an alkyne adds to an unsa turated alkoxychromium carbene 11 togive a hydroquinone-chromium complex 12 . Decomplexation yields thearomatic compound (Scheme 10.30).

Scheme 10.30The annulation reaction is formally a [3 + 2 + 11 cycloaddition of thecarbene, alkyne and a CO molecule. The connectivity is shown in 13.

13


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Oxidation and Reduction ofAromatic Compounds

11.I IntroductionThe unusual stability of the aromatic sextet suggests that benzene willbe resistant to oxidation and reduction of the ring, since both processeswill destroy the aromaticity. Although this is generally the case, bothtypes of reaction are possible under certain conditions. This chapter isrestricted to benzene and its derivatives, but other aromatic systems aremore easily oxidized and reduced (see Chapter 12).1I 2 Reduction of the Benzene Ring111211 ydrogenationWe have seen in Chapter 1 that benzene may be hydrogenated to cyclo-hexane, although the associated loss of resonance energy makes thisprocess more difficult than for simple alkenes. Moreover, because theinitial product, cyclohexadiene, is reduced more rapidly than benzene,hydrogenation results in complete rather than partial reduction (Scheme11.1). Scheme 11.1Cyclohexane, cyclohexene and cyclohexadiene are used as hydrogensources in the hydrogenation of alkenes to alkanes, when they are them-selves oxidized to benzene. In these reactions, the driving force is the for-mation of the aromatic ring.

129


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1I 2.2 Alkali Metal-Ammonia Reduction

Scheme 11.2

The p artial reduction of arenes can be achieved using theAn alkali metal (lithium, sodium or potassium) is dissolved inliquid ammonia in the presence of the arene, an alcohol, such as2-methylpropan-2-01 (tert-butyl alcohol) and a co-solvent to assistsolubility.A solution of sodium in ammonia may be considered as a source ofsolvated electrons. The alcohol functions as a proton source. The aro-matic molecule accepts an electron from the solution to form a radicalanion 1, proto nation of which by the alcohol forms the radical 2 (Scheme11.2). Acceptance of a second electron generates a new carba nion , whichis also proton ated and gives the 1,4-diene 3. The overall transformationis reduction of the aromatic compo und to the 1,4-diene.

H H

NH3, RO HH H H1 2 3

It might be expected that the more reactive metals would be thosewith the lower ionization potential, but in practice lithium is the mostreactiv

51862392 027 aromatic chemistry

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