Chem 5011

organic chemistry

Huckle's rule

Planar, fully conjugated, monocyclic systems (one ring of p orbitals) with (4n + 2) pi electrons have a closed shell of electrons all in bonding orbitals and are exceptionally stable. Such systems are said to be aromatic.

Analogous systems with 4n pi electrons are described as anti-aromatic

General Electrophilic aromatic substitution (SEAr) of benzene

Bromination/chlorination of benzene reaction scheme

Bromination/chlorination of benzene generation of electrophile

Bromination/chlorination of benzene mechanism

Nitration of benzene reaction scheme

Nitration of benzene generation of electrophile

Nitration of benzene mechanism

Sulfonation of benzene: reaction mechanism

Sulfonation of benzene: generation of electrophile

Sulfonation of benzene: mechanism

Desulfonation: reaction scheme

Desulfonation: mechanism

Friedel-crafts alkylation: reaction scheme

Friedel-crafts alkylation: generation of electrophile

Friedel-crafts alkylation: mechanism

Friedel-crafts acylation: reaction scheme

Friedel-crafts alkylation: alternatives to RCl/AlCl3

Friedel-crafts acylation: generation of electrophile

Friedel-crafts acylation: mechanism

Friedel-Crafts acylation to access to primary alkyl groups: Clemmensen reduction -> reaction scheme

Friedel-Crafts acylation to access to primary alkyl groups: Wolff-Kishner reduction -> reaction scheme

Friedel-Crafts acylation to access to primary alkyl groups: Wolff-Kishner reduction -> mechanism

Effects of substituents on rate of SEAr reaction: Electron donating groups

• Donate electron density to the benzene ring

• Activating groups (double bond more nucleophilic)

• EDG-substituted benzene more reactive than benzene

• Examples of EDG: NR2 , OR, SR, alkyl, aryl

Effects of substituents on rate of SEAr reaction: Electron withdrawing groups

• Withdraw electron density from the benzene ring

• Deactivating groups (double bond less nucleophilic)

• EWG-substituted benzene less reactive than benzene

• Examples of EWG: NO2, SO3H, CO2R, C=O, CN, CF, halides

How to identify EWG

Double bonds from benzene ring can be delocalised onto electronegative atom of

substituent, revealing a positive charge in the benzene ring

Other EWG: perfluoro alkyl groups by negative inductive effect (also called negative

hyperconjugation)

How to identify EDG

Lone pair on EDG can be delocalised revealing a negative charge in benzene ring:

lone pair donation

Other EDG: alkyl groups by pi-donation also called positive inductive effect or

hyperconjugation

Activating ortho/para (o/p) directing groups (R = EDG)

• Positive mesomeric effect (lone pair or π-bond donation): +M

• Examples: OH, OR, NR2

, SR, Ph

• Positive inductive effect (σ bond donation): +I

• Example: Alkyl groups

Deactivating meta (m) directing groups (R = EWG)

• Negative mesomeric effects (delocalisation of benzene double

bonds onto R group): −M

• Examples: NO2, SO3H, CO2R, C=O, CN

• Negative inductive effects (through σ bond): −I

• Examples: CF3 (and fluoroalkyls)

Deactivating ortho/para (o/p) directing groups (R = halogen)

+M (lone pair donation) and −I (electronegativity of halogen)

Dose mesomeric or inductive effects have a greater effect on directing effect?

generally M > I

Reactivity of multisubstituted benzenes: Rules to predict outcome

Consider the directing effects of each group in turn. You never get substitution

at a position that is occupied with a group

• +M more directing than +I more directing than −M more directing than −I

(+M > +I > −M > −I)

• “Never” get substitution between two meta substituents.

• Sterics can also have an impact