16- Benzene Reactions

Benzene Reactivity

• reactions preserve aromatic core

• resists addition reactions that would break aromaticity

• substituents impact reaction rate & orientation

What kind of reaction does benzene do?

electrophilic aromatic substitution reactions (EAS)

Types of EAS Reactions

• halogenation (Cl, Br, I)

• nitration (NO2)

• sulfonation (SO3H)

• alkylation (R)

• acylation (COR)

General Mechanism of EAS Reactions

• need Lewis acid catalyst (accepts electrons)

• makes sigma complex intermediate

• has resonance stabilization

• regenerates aromatic system by losing a proton

Sigma Complex

What are the 2 main substituent effects?

activating groups → react faster than benzene

deactivating groups → react slower than benzene

Activating Groups

• react faster than benzene

• donate electrons

• direct substitution to ortho/para positions

• OH, NH2, alkyl

Deactivating Groups

• react slower than benzene

• withdraw electrons

• direct to meta position

• NO2, CN, COOH

Factors Influencing Substituent Effects

inductive effects & resonance effects

How do inductive effects impact substituent effects?

electron withdrawal/donation through sigma bonds, controlled by EN

How do resonance effects impact substituent effects?

• electron movement through pi system

• de/stabilizes intermediate

What is the caveat for directing effects?

directing effects can reinforce or compete

Are multiple substituents a good thing?

yes/no, multiple substituents interact predictably

What occurs with steric hindrance?

steric hindrance influences product distribution

Oxidation

convert alkyl side chains to carboxylic acids, LOSE electrons

Reduction

selective hydrogenation, GAIN electrons

Nucleophilic Substitution

possible with electron withdrawing groups

Electron Withdrawing Groups

CN, NO2, C=O, halogens,

• inductive → pull electron density towards themselves through sigma bonds

• resonance → can delocalize electrons through resonance, effectively pulling electron density away from the rest of the molecule

Why are halogens considered deactivating despite being ortho/para directing?

inductive electron-withdrawal outweighs resonance donation

What is a key structural feature of the benzyne intermediate?

has a highly strained triple bond with sp2 hydrbidization

What advantage does Friedel-Crafts acylation have over akylation?

acyl carbocations don’t rearrange & multiple acylations don’t occur

What is the major limitation of Friedel-Crafts alkylation that makes primary carbocations problematic?

primary carbocations are too unstable and likely form complexes with Lewis acids

What makes meta-directing deactivators like nitro groups (NO2) so strongly deactivating?

withdraw electrons inductively & through resonance

What determines whether a substituent is ortho/para directing vs meta directing?

whether the substituent stabilizes the sigma complex at ortho/para or meta positions

Which catalyst is required for the bromination of benzene & why?

FeBr3 to polarize bromine & make it more electrophilic

What is the key characteristic of the sigma complex intermediate formed during electrophilic aromatic substitution?

resonance stabilized but not aromatic due to an sp3 carbon

When 2 substituents on a benzene ring have opposing directing effects, what determines the outcome?

more powerful activating groups determines the principal outcome

Why do carbocation rearrangements occur during Friedel-Crafts alkylation?

carbocations rearrange to form more stable structures through H or alkyl shifts

Why can alkyl side chains of aromatic compounds be oxidized to carboxylic acids, while aromatic ring remains intact?

oxidizing agents selectively attack benzylic positions due to radical stability

What makes the nitronium ion (NO2+) such a powerful electrophile in nitration reactions?

has a formal positive charge on nitrogen

Nucleophile vs Electrophile

Nucleophile → donates an electron pair to form a chemical bond, electron rich

Electrophile → accepts an electron pair, electron poor

What principle guides the synthesis of polysubstituted benzenes?

Order of substitution must consider the directing effects of each group

What makes hydroxyl (OH) & amino (NH2) groups such strong activators despite containing EN atoms?

donate electron density through resonance using their lone pairs

Why are alkyl groups considered activating & ortho/para directing?

Donate electrons through inductive effects, stabilizing the sigma complex

Why doesn’t benzene undergo addition reactions like alkene when treated with Br2?

Addition would destroy aromaticity, making it energetically unfavorable

Why is sulfonation of benzene considered a reversible process?

Desulfonation can occur by heating in dilute H2SO4

What conditions are required for nucleophilic aromatic substitution to occur?

Electron-withdrawing groups ortho or para to the leaving group

Why does steric hindrance affect the ortho/para ratio in electrophilic aromatic substitution?

Large substituents block access to ortho positions, favoring para substitution

How does the Clemmensen reduction complement Friedel-Crafts acylation in synthesis?

Converts carbonyl group to a methylene group, allowing synthesis of alkylbenzenes that can’t be made directly