Organic 2 -chapter 16- Dr.Naem al saed -

8/7/2019 Organic 2 -chapter 16- Dr.Naem al saed -

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eactions of Substituted Benzenes: Effects of Substituents on

eactivity and Orientation

he slow step of an electrophilic aromatic substitution reactio

the formation of the carbocation intermediate:

he nature of groups already on an aromatic ring affect bot

he reactivityandorientation of future substitution.

Reactivity:Electron-donating substituents (Activating groups) increase th

ate of substitution reactions by stabilizing the carbocatio

termediate. Activating groups cause the aromatic ring to bmore reactive than benzene.

All activating groups are also ortho-para directors.

p- o-


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Electron-withdrawing substituents (Deactivating groups)

ecrease the rate of substitution reactions by destabilizing

he carbocation intermediate. Deactivating groups cause the

romatic ring to be less reactive than benzene.

Deactivating Groups are Meta Directors

m-

ectron Donation and Electron Withdrawal occur by:esonance

nductive (sigma-bond)

yperconjugation


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Resonance Electron Donation and Withdrawal

ubstituents such as NH2 (NHR, NR2), OH (OR) donate electron

y resonance, but they also withdraw electrons inductivel

Electron donation into the benzene ring by resonance is mor

gnificant than inductive electron withdrawal from the ring)

hese groups are ortho,para-directing substituent


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An ortho,para-directing substituent:


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esonance donation into the benzene ring competes with

esonance donation into the carbonyl. These substituents are

ss effective in donating electrons into the ring because


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Substituents such as C=O, CN, SO3H, and NO2withdraw electrons by resonance: These groups

are m-directors.


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hese substituents are powerful electron-withdrawing groups:

xcept for the ammonium ions, these substituents withdraw

ectrons both inductively and by resonance.


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ll activating substituents are orthopara directors:


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ectron-withdrawing groups stabilize a base and therefore

ncrease the strength of its conjugate acid

ectron-donating groups destabilize a base and thus

ecrease the strength of its conjugate acid

The Effect of Substituents on pKa


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The more electronic deficient a substituent on phenol, the

stronger the acid:

o understand the relative pKa values, consider th

elocalization of the phenolate anion (stars show anio

istribution):

Unstable

Stable: through resonance

of anion into nitro

More stable anion =

lower pKa


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he more electronic deficient a substituent on benzoic acid,

he stronger the acid:

ubstituent effect on pKa is minimal in benzoic acids because

nly inductive electronic effects are present:

he more electronic deficient a substituent on a protonated

niline, the stronger the acid:


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he orthopara product ratio decreases with an increase

n the size of the substituents:


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A benzene ring with a meta director cannot

undergo a FriedelCrafts reaction:

Methoxy and hydroxy substituents are so strongly activating

hat halogenation is carried out without a Lewis acid:


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n designing a disubstituted benzene, consider the order of

substitution:


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he FriedelCrafts acylation must be carried out first, becaus

he nitro group is strongly deactivating:


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n the synthesis ofpara-chlorobenzoic acid from toluene,

he methyl group is oxidized after chlorination:

In the synthesis ofmeta-chlorobenzoic acid, the methylgroup is oxidized before chlorination:

How is the meta derivative prepared?

FriedelCrafts acylation-Sulfonation-Carbonyl reduction


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Synthesis of Trisubstituted Benzenes

Steric hindrance makes the position between the

substituents less accessible


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A strongly activating substituent will win out over a weakly

activating substituent or a deactivating substituent


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Synthesis of Substituted Benzenes Using Arenediazonium

Salts : Preparation of the Diazonium Salt

Mechanism: See the Textbook


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Nucleophilic Aromatic Substitution Reactions

Nucleophilic aromatic substitution reactions require at least

one strongly electron-withdrawing substituent to occur:

Electron-withdrawing substituents increase the reactivity of the

benzene ring toward nucleophilic substitution and decrease the

reactivity of the benzene ring toward electrophilic substitution


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he electron-withdrawing substituents must be ortho or para to

he site of nucleophile attack,

o that electrons of the attacking nucleophile can be

elocalized into these substituents


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Organic 2 -chapter 16- Dr.Naem al saed -