substituição aromática_pba15

8/17/2019 Substituição Aromática_PBA15

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Péricles B. Alves Péricles B. Alves Péricles B. Alves Péricles B. Alves Péricles B. Alves Péricles B. Alves Péricles B. Alves Péricles B. Alves


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1. Isolamento e Estrutura do benzeno

2. Compostos aromáticos naturais e sintéticos

3. Critérios de aromaticidade para um composto4. Reatividade

4.1. Mecanismo geral da reação de substituição eletrofílica

BENZENO E AROMATICIDADE

5. Reações dos substituintes no benzeno6. O efeito dos substituintes na reatividade

7. O efeito dos substituintes na orientação da substituição

8. Reações de oxidações; Reações de reduções


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Isolamento e estrutura do benzeno

Isolado pela primeira vez por Michael

Faraday em 1825

Aromatico em referencia ao aroma ou

cheiro em o osi ão ao alifático.

Foi um dos compostos orgânicos mais

estudados.Primeiro ex. de composto contendo

ligações deslocalizadas.

Michael Faraday



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MeO

Anetol

HO

CH3O CHO

"Extrato erva doce"Vanilina

CH3O

HO

CHO

Reconhecimento de compostos aromáticos apenas pelo odor

Eugenol Cinamaldeído

OH

(-)-Mentol

Neste caso um grande equivoco

do critério odor


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Muito importante na industria química


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Aromaticidade

HIDROCARBONETOS

Alifáticos Aromáticos

alcanos alcenos alcinos



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I II(Dewar)

III(Ladenburg)

IV

CH3 C C C C CH3CH2 CH C C CH CH2

V VI



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O benzeno reagia somente sob condições vigorosas

ou com Br 2 /FeBr

3:

Produto: C6H5Br (produto monobromado)

- todos os H eram equivalentes!!!

VIV

IVIII(Ladenburg)

II(Dewar)

I

CH2 CH C C CH CH2 CH3 C C C C CH3



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Reagente Produto

∆∆∆∆ H ohidrogenação

(kJ/mol) (kcal/mol)

ciclohexeno ciclohexano -206 -28,2

benzeno

1,3-ciclohexadieno ciclohexano

ciclohexano -118

-230 -55,0

-49,2


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COOH

COOH

Cl

OH

HCl

H3O+

KMnO4

ciclohexeno

Porque era tão estável e inerte as reações químicas?

benzeno

KMnO4

H3O+

HClnão reage

não reage

não reage


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• The 6 p-orbitals combine to give

▫ 3 bonding orbitals with 6 π e-s,

▫ 3 antibonding with no electrons

• Orbitals with same energy are degenerate

Molecular Orbital Description of Benzene


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Aromatic ring oriented perpendicular to a strong magneticfield, delocalized π electrons producing a small local

magnetic fieldOpposes applied field in middle of ring but reinforces

applied field outside of ring

Ring CurrentsRing Currents


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Propiedades Espectroscopicas do Benzeno


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1H NMR: Aromatic H’s strongly deshielded by ring and absorb between δ 6.5 and δ 8.0

1H NMR Espectroscopia do grupo Aromatico


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• IR: Aromatic ring C–H stretching at 3030 cm−−−−1 & peaks 1450 -1600 cm−−−−

Infravermelho (IR): Espectroscopia de aromáticos

The IR spectra of benzene and its derivatives

have characteristic bands at:

•3030 cm-1 phenyl-H stretching

•1500-2000 cm-1 aromatic C-C stretching

•650-1000 cm-1

C-H out of plane bending


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Espectrometria de massas de compostosaromáticos


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• In benzene, the actual bond length (1.39 Å) is intermediate

between the carbon—carbon single bond (1.53 Å) and thecarbon—carbon double bond (1.34 Å).


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The Criteria for Aromaticity—Hückel’s Rule

Four structural criteria must be satisfied for a compound to bearomatic.

[[11]] AA moleculemolecule mustmust bebe cycliccyclic..

To be aromatic, each p orbital must overlap with p orbitals on adjacent atoms.

Erich Hückel


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[[22]] AA moleculemolecule mustmust bebe planar planar..

Todos os orbitais p adjacentes devem estar alinhados paraque a densidade de elétrons π posa ser deslocalizada.

Since cyclooctatetraene is non-planar, it is not aromatic, and it undergoes additionreactions just like those of other alkenes.



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Non-aromatic

• Cyclooctatetraene has four double bonds, reacting with Br2,KMnO4, and HCl as if it were four alkenes

• Distorts out of plane so C=C’s behave like ordinary alkenes

The molecular structure of cyclooctatetraene is non-planar and tub shaped.The double bonds are nearly orthogonal and are not conjugated.


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[[33]] AA moleculemolecule mustmust bebe completelycompletely conjugatedconjugated.

Aromatic compounds must have a p orbital on everyatom.



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[[44]] AA moleculemolecule mustmust satisfysatisfy HHüückel’sckel’s rule,rule, andand

containcontain aa particular particular number number of of ππππππππ electronselectrons..

Hückel's rule:

6 π electrons. Cyclobutadiene is antiaromatic and especiallyunstable because it contains 4 π electrons.


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Note that Hückel’s rule refers to the number of π electrons, not the number of atoms in aparticular ring.


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• Two or more six-membered rings with alternating double and single

bonds can be fused together to form polycyclic aromatichydrocarbons (PAHs).

• There are two different ways to join three rings together, forminganthracene and phenanthrene.

• As the number of fused rings increases, the number of resonance

structures increases. Naphthalene is a hybrid of three resonancestructures whereas benzene is a hybrid of two.


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1,3-Cyclopentadienecontains conjugated C=C’s

joined by a CH2 that blocksdelocalization

Removal of H+ at the CH2 pro uces a cyc c π e-

system, which is stable

Removal of H- or H•generate nonaromatic 4

and 5 electron systems

Relatively acidic (p K a = 16) because the anion is stable

Antiaromatic

(unstable)Antiaromatic

(unstable)

Aromatic

(very stable)


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Cycloheptatrienyl Cation

3 conjugated C=C’s joined by a CH2

Removal of “H-”

leaves the cation The cation has 6πe-s

and is aromatic

Aromatic

(stable)

Antiaromatic

(unstable)

Antiaromatic

(very unstable)


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Substituição Electrofilica Aromatica (SEA)



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Reação de Substituição Eletrofilica

Aromática (SEA):• Reactions typical of addition to alkenes do not work on aromatic double bonds.

Need more electrophilic (more positive) halogen in orderto break an aromatic double bond.


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• The energy changes in electrophilic aromatic substitution are

shown below:


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SEA ocorre em dois passos: AdiçãoAdição seguido de EliminaçãoEliminação

• FeBr3 acts as a catalyst to polarize the bromine reagent and

so make it more positive (more electrophilic)• The π electrons of the aromatic ring act as a nucleophiletoward the now more electrophilic Br2 (in the FeBr3 complex)

SEA: Bromação

The cationic addition intermediate is called a sigma complex



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• The cationic addition intermediatetransfers a proton to FeBr4- (from Br-

and FeBr3)

• This restores aromaticity (in contrast

with addition in alkenes)



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• Chlorine and iodine (but not fluorine, which is too reactive) canproduce aromatic substitution products

Chlorinationrequires FeCl3

Iodine must beoxidized (with

Cu+ or peroxide)to form a more

powerful I+

species


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Halogenação

• In halogenation, benzene reacts with Cl2 or Br 2 in the presence of a Lewis acidcatalyst, such as FeCl3 or FeBr 3, to give the aryl halides chlorobenzene or bromobenzene respectively.

• Analogous reactions with I2 and F2 are not synthetically useful because I2 is too

unreactive and F2 reacts too violently.


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•• Chlorination proceeds by a similar mechanism.Chlorination proceeds by a similar mechanism.


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• Benzene ring reacts with fuming sulfuric acid (amixture of H2SO4 and SO3) to yield benzenesulfonicacid

– The reactive electrophile is either HSO3+ or neutral

SO3 depending on reaction conditions

SulfonaçãoSulfonação


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– The reactive electrophile is either sulfur trioxide SO3or its conjugate acid HSO3

+

Nitração


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Nitração

• The combination of nitric acid and sulfuric acid produces NO2+

(nitronium ion)• The reaction with benzene produces nitrobenzene

• The Nitro group can be reduced to an Amino group if needed


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• Outro método: dissolver HNO3 em anidrido

acético: gera nitrato de acetila

• Um procedimento conveniente

• A nitrição pode ser catalisada por sais delatanídeos



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Desvantagens da alquilação:

•Produtos derearranjos•Produtospolialquilados

Produtos rearranjados:

Me3CCH

2Cl/ AlCl

3 +

2 2

Me3C CH3

+

Me2C CH2Me

A mesma reação com FeCl3

Me3CCH2Ph (produto não rearranjado).


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intramolecular para gerar anéis fundidos;sendo anéis de 6 mais fáceis de formar que

anéis de 5

AlquilaçãoAlquilação dede FriedelFriedel--CraftsCrafts

CharlesCharles FriedelFriedel

James Mason CraftsJames Mason Crafts


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Mechanism for AlkylationMechanism for Alkylation Mechanism forMechanism for AcylationAcylation

Water is required here


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•• FriedelFriedel--Crafts alkylationCrafts alkylation – is an electrophilicaromatic substitution in which the electrophile isa carbocation, R+.

– AlCl3 catalyst promotes the formation of the alkyl, , ,

– The Wheland (carbocation) intermediate forms

– Alkylation is the attachment of an alkyl group tobenzene; R+ substitutes for H+



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FriedelFriedel--Crafts Alkylation andCrafts Alkylation and FriedelFriedel--CraftsCrafts AcylationAcylation


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FriedelFriedel--CraftsCrafts AlkylationAlkylation andand FriedelFriedel--CraftsCrafts AcylationAcylation

• In Friedel-Crafts alkylation, treatment of benzene with an alkyl halide and a Lewisacid (AlCl3) forms an alkyl benzene.



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[[22]] RearrangementsRearrangements cancan occur occur..

These results can be explained by carbocation rearrangements.


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FriedelFriedel--Crafts Alkylation Reaction:Crafts Alkylation Reaction: MechanismMechanism


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• Aromatic ring activates neighboring carbonylgroup toward reduction

• Ketone is converted into an alkylbenzene by

catalytic hydrogenation over Pd catalyst


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• In Friedel-Crafts acylation, a benzene ring is treated with an

acid chloride (RCOCl) and AlCl3 to form a ketone.• Because the new group bonded to the benzene ring is called

an acyl group, the transfer of an acyl group from one atom to

another is an acylation.


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• In Friedel-Crafts acylation, the Lewis acid AlCl3 ionizes thecarbon-halogen bond of the acid chloride, thus forming apositively charged carbon electrophile called an acylium ion,which is resonance stabilized.

• The positively charged carbon atom of the acylium ion thengoes on to react with benzene in the two step mechanism of electrophilic aromatic substitution.


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• Benzene ring reacts with a carboxylic acid chloride,RCOCl, in the presence of AlCl3 catalyst to yield anacylbenzene

– Acylation is the attachment of an acyl group,-COR,to benzene; RCO+ substitutes for H+


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•• FriedelFriedel--Crafts acylationCrafts acylation – is an electrophilic aromaticsubstitution in which the reactive electrophile is aresonance-stabilized acyl cation, RCO+.

– AlCl3 catalyst promotes the formation of the acyl+ , , ,

– The acyl cation, RCO+, does not rearrange; it isresonance-stabilized

– The Wheland (carbocation) intermediate forms



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– – The mechanism ofThe mechanism of FriedelFriedel--CraftsCrafts acylationacylation isissimilar tosimilar to FriedelFriedel--Crafts alkylationCrafts alkylation


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• Similar to alkylation• Reactive electrophile: resonance-stabilized acyl cation

• An acyl cation does not rearrange

• Can reduce carbonyl to get alkyl product


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MethodologiesMethodologies UsedUsed for for thethe ReductionReduction StepStep



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The energy diagrams below illustrate the effect of electron-withdrawing

and electron-donating groups on the transition state energy of the rate-determining step.

EfeitoEfeito dodo SubstituenteSubstituente


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E++E

Substituintes que doam eletrons tornando mais nucleofilico. Gru o Doador de Electrons de ativam o anel nas rea ões de SEA

EfeitoEfeito dodo SubstituenteSubstituente

Substituinte que retiram eletrons tornando o anel pouconucleofilico. Grupo Retirador de Electrons (gre) desativam o anel nas reações

de SEA


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Efeito do Substituinte


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Os substituintes afetam a reatividade do anel


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Substituents may

activateactivate the ring, make it (much) more reactive than

benzene or

deactivatedeactivate the ring, make it (much) less reactive

aromático.

an enzene

Classification of Substituent EffectClassification of Substituent Effect


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Substituents can be classified as:

ortho- and para-directing activators,

ortho- and para-directing deactivators, and meta-directing deactivators


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Reactivity and orientation in electrophilic aromaticsubstitutions are controlled by an interplay of inductiveinductiveeffectseffects and resonanceresonance effectseffects:

– – Inductive effect Inductive effect - withdrawal or donation of electronsthrough a σσ bondbond

– – Resonance effect Resonance effect - withdrawal or donation ofelectrons through a ππ bondbond



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Inductive effectsInductive effects - withdrawal or donation of electronsthrough a σ bond due to electronegativity and polarityof bonds in functional groups

Halogens, C=O, CN, and NO2 groups inductivelywithdraw electrons through σ bond connected toring

Alkyl groups inductively donate electrons



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Resonance effectResonance effect - withdrawal or donation of electronsthrough a π bond due to the overlap of a p orbital onthe substituent with a p orbital on the aromatic ring

C=O, CN, and NO2 groups withdraw electrons fromthe aromatic ring by resonance

Halogen, OH, alkoxyl (OR), and amino substituentsdonate electrons to the aromatic ring by resonance


OrthoOrtho-- and Paraand Para--Directing Deactivators: HalogensDirecting Deactivators: Halogens


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•• Halogens are deactivatingHalogens are deactivating

– They have a strong electronstrong electron--withdrawing inductivewithdrawing inductive

and a weak electron-donating resonance effect

•• Halo ens areHalo ens are orthoortho andand araara directorsdirectors

– The orthoortho and para para intermediatesintermediates are the moststabilized stabilized (lower in energy)

– Halogens stabilizestabilize the positive charge by resonanceby resonancedonation of a lone pair of electronsdonation of a lone pair of electrons

ContrastingContrasting EffectsEffects:: InductiveInductive vsvs ResonanceResonance


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• When the two effects act in opposite direction, thestrongest effects dominate.

– -

ContrastingContrasting EffectsEffects:: InductiveInductive vsvs ResonanceResonance

due to electronegativity

– Halogens have electron-donating resonance effects dueto lone-pair electrons

– Resonance interactions are generally weaker, affectingorientation. Thus, halogens deactivate the ring


C O CN d NO ithd l t f


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C=O, CN, and NO2

groups withdraw electrons fromthe aromatic ring by resonance

π electrons flow from the ring to the substituents,placing a positive charge in the ring

– Z is more electronegative than Y


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Halogen, OH, alkoxyl (OR), and amino substituentsdonate electrons to the aromatic ring by resonance

π electrons flow from the substituents to the ringsplacing a negative charge in the ring

– Y has a lone pair of electrons

Resonance effects are only observed with substituents containing lone pairs or πbonds


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bonds.

An electron-donating resonance effect is observed whenever an atom Z having alone pair of electrons is directly bonded to a benzene ring.


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Halogens, C=O, CN, and NO2 inductively withdraw electrons through σ bond connected to ring

An Explanation of SubstituentAn Explanation of SubstituentAn Explanation of SubstituentAn Explanation of Substituent


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•• ActivatingActivating groupsgroups donatedonate electronselectrons toto thethe ringring,,stabilizingstabilizing thethe WhelandWheland intermediateintermediate ((carbocationcarbocation))

An Explanation of SubstituentAn Explanation of Substituent

EffectsEffects

An Explanation of SubstituentAn Explanation of Substituent

EffectsEffects

, , 2 an

•• DeactivatingDeactivating groupsgroups withdrawwithdraw electronselectrons fromfrom thethering,ring, destabilizingdestabilizing thethe WhelandWheland intermediateintermediate

CN, C=O, NO2 and X


OrthoOrtho-- and Paraand Para--Directing Activators: AlkylDirecting Activators: Alkyl


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•• Alkyl groups are activatingAlkyl groups are activating

– They have an electronelectron--donating inductivedonating inductive effect

•• Alkyl groups areAlkyl groups are orthoortho andand parapara directorsdirectors

– The orthoortho and para para intermediatesintermediates are the moststabilized stabilized (lower in energy)

– The positive charge is directly on the alkyl-substituted carbon (33oo carboncarbon) and is stabilized stabilized by by thethe inductiveinductive electronelectron--donating donating effect of the alkylgroup

• The positive charge is directly on the alkyl-substitutedoo


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carbon (33oo

carboncarbon) and is stabilized by the inductivestabilized by the inductiveelectronelectron--donating effect of donating effect of the alkyl group

OrthoOrtho-- and Paraand Para--Directing Activators: OH and NHDirecting Activators: OH and NH22


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•• OH, OR and NHOH, OR and NH22 groups are activatinggroups are activating

– They have a strong electronstrong electron--donating resonancedonating resonance

and a weak electron-withdrawing inductive effect

•• OH OR and NHOH OR and NH rou s are ortho and ara directorsrou s are ortho and ara directors

– The orthoortho and para intermediates para intermediates are the moststabilized stabilized (lower in energy)

– The positive charge is stabilized by resonancestabilized by resonancedonation of an electron pair donation of an electron pair from O or N


• The ortho and para intermediates are more stablemore stable because


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pof resonance donation of an electron pair resonance donation of an electron pair from O or N

• The ortho and para intermediates are more stablemore stable because


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pof resonance donation of an electron pair resonance donation of an electron pair from X

MetaMeta--Directing DeactivatorsDirecting Deactivators


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•• All metaAll meta--directing groups are strongly deactivatingdirecting groups are strongly deactivating

– They have electron-withdrawing inductive andresonance effects that reinforce each other

– The orthoortho and para para intermediatesintermediates are destabilized destabilized

– The positive charge of the carbocation intermediatein ortho and para attack is directly on the carbon

that bears the deactivating group and resonancecannot produce stabilization


• The meta intermediate is more stablemore stable because resonance


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does not place the positive charge directly on the carbonthat bears the deactivating group

• An electron-withdrawing resonance effect is observed in substituted benzenes


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having the general structure C6H5-Y=Z, where Z is more electronegative thanY.

• Seven resonance structures can be drawn for benzaldehyde (C6H5CHO).Because three of them place a positive charge on a carbon atom of the benzene

ring, the CHO group withdraws electrons from the benzene ring by a resonanceeffect.


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• The inductive and resonance effects in com ounds havin the eneralstructure C6H5-Y=Z (with Z more electronegative than Y) are both

electron withdrawing.

• These compounds represent examples of the general structural features in


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electron-donating and electron withdrawing substituents.


• Consider toluene—Toluene reacts faster than benzene in all substitutionreactions.


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• The electron-donating CH3 group activates the benzene ring to electrophilicattack.

• Ortho and para products predominate.

• The CH3 group is called an ortho, para director .

• Consider nitrobenzene—It reacts more slowly than benzene in all substitutionreactions.


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• The electron-withdrawing NO2 group deactivates the benzene ring to electrophilicattack.

• The meta product predominates.

• The NO2 group is called a meta director .

All substituents can be divided into three general types:


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• Keep in mind that halogens are in a class by themselves.

• Also note that:


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• To understand how substituents activate or deactivate the ring, wemust consider the first step in electrophilic aromatic substitution.


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• The first step involves addition of the electrophile (E+) to form aresonance stabilized carbocation.

• The Hammond postulate makes it possible to predict the relative rate

of the reaction by looking at the stability of the carbocationintermediate.

• The principles of inductive effects and resonance effects can now beused to predict carbocation stability.


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OrientationOrientation EffectsEffects inin SubstitutedSubstituted BenzenesBenzenes


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• There are two general types of ortho, para directors and one general type of metadirector.

• All ortho, para directors are R groups or have a nonbonded electron pair on theatom bonded to the benzene ring.

• All meta directors have a full or partial positive charge on the atom bonded to the.

• A CH3 group directs electrophilic attack ortho and para to itself

because an electron donating inductive effect stabilizes the


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because an electron-donating inductive effect stabilizes thecarbocation intermediate.

• An NH2 group directs electrophilic attack ortho and para to itself because the carbocation intermediate has additional resonancestabilization


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stabilization.

• With the NO2 group (and all meta directors) meta attack occursbecause attack at the ortho and para position gives a destabilized

carbocation intermediate


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carbocation intermediate.

• Benzene rings activated by strong electron-donating groups—OH

LimitationsLimitations inin ElectrophilicElectrophilic AromaticAromatic SubstitutionsSubstitutions


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Benzene rings activated by strong electron donating groups OH,NH2, and their derivatives (OR, NHR, and NR2)—undergopolyhalogenation when treated with X2 and FeX3.

NO2 NHNO2 NH


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Fe, H3O+

-OH

SnCl2 H3O+

NO2

NO2

NH2

NH2

Fe, H3O+

-OH

SnCl2 H3O+

NO2

NO2

NH2

NH2

H2, Pd/C

EtOH

-

OH

NO2 NH2

H2, Pd/C

EtOH

-

OH

NO2 NH2


Summary of Substituent Effects in Aromatic Substitution


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DisubstitutedDisubstituted BenzenesBenzenes

1. When the directing effects of two groups reinforce, the new substituent isl t d th iti di t d b b th


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g g plocated on the position directed by both groups.

2. If the directing effects of two groups oppose each other, the more powerfulactivator “wins out.”


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3. No substitution occurs between two meta substituents because of crowding.


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SynthesisSynthesis of of BenzeneBenzene DerivativesDerivatives

In a disubstituted benzene, the directing effects indicate which substituent must bedd d t th i fi t


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added to the ring first.

Let us consider the consequences of bromination first followed by nitration, andnitration first, followed by bromination.


Pathway I, in which bromination precedes nitration, yields the desiredproduct. Pathway II yields the undesired meta isomer.


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1.1. If the directing effects of the two groups are theIf the directing effects of the two groups are thesame the result is additivesame the result is additive


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g g pg g psame, the result is additivesame, the result is additive

– It gives a single product

2.2. If the directing effects of two groups oppose eachIf the directing effects of two groups oppose eachother the more powerful activating group determinesother the more powerful activating group determines


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g gg gother, the more powerful activating group determinesother, the more powerful activating group determinesthe principal outcomethe principal outcome

– It usually gives mixtures of products

3.3. The position between the two groups in metaThe position between the two groups in meta--disubstituted compounds is unreactivedisubstituted compounds is unreactive


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disubstituted compounds is unreactivedisubstituted compounds is unreactive

– The reaction site is too hindered

– To make aromatic rings with three adjacentsubstituents, it is best to start with an ortho-disubstituted compound



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substituição aromática_pba15

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