electrophilic aromatic substitution

why is a lewis acid catalyst used for electrophilic substitution?

bromine must be activated by lewis acid (electron acceptor)

why is addition slow and elimination fast?

slow because breaking aromaticity

fast because restoring aromaticity

how does the lewis acid get involved in electrophilic substitution reaction (e.g. AlCl₃)

what are electrophilic substitution steps for Br₂ reacting with benzene?

what is the energy profile diagram of electrophilic substitution?

higher activation energy for first step as breaking aromaticity

what is the reaction for nitration?

how is the nitronium ion formed? (from HNO₃ and H₂SO₄)

what is the mechanism for nitration?

what is the sulfonation reaction?

mechanism for protonation of sulfur trioxide (SO₃ and H₂SO₄)

what is the mechanism for sulfonation?

what is the friedel crafts acylation reaction?

mechanism for formation of acylium ion (acyl chloride and AlCl₃)

friedel crafts acylation mechanism

what is the friedel crafts alkylation for tertiary alkyl chloride?

primary alkyl chloride friedel crafts alkylation

what is Clemmensen Reduction?

what is the conditions?

NaBH₄

what are the conditions?

H₂SO₄

what are the conditions?

H₂ / Pd

where is the ortho position?

where is the meta position?

where is the para position?

if X is an electron donating group, how does this affect electrophilic substitution reactions?

rate? position?

rate increases

happens preferentially at ortho and para

if X is an electron withdrawing group, how does this affect electrophilic substitution reactions?

rate?

positons?

rate decreases

happens preferentially at meta

where does electrophilic attack occur?

at carbons with highest electron density

what does a lower chemical shift mean?

more shielding

more electron density

more nucleophilic

does electron rich or deficient aromatics react faster?

electron rich reacts faster

show resonance of phenol

what does a higher chemical shift mean?

less shielding

less electron density

less nucleophilic

show resonance

how does positive charges (electron withdrawing) affect positions?

deactivates ortho/para

least deactivated is meta which is why reactions happen here

how do inductive electron withdrawing groups affect position?

activate/deactivate?

strongly deactivating and meta directing

meta most likely, then ortho

how do inductive electron donating groups affect position?

activating/deactivating?

weak activating and ortho/para directing

ortho most likely, then para

how do electron donating groups affect positive charge on ipso carbon?

what substitution position is favoured?

stabilises positive charge

ortho/para substitution favoured

how do electron withdrawing groups affect positive charge on ipso carbon?

what substitution position is favoured?

positive charge destabilised

meta substitution favoured

diagram of ortho substitution and resonance structures stabilising positive charge on ipso carbon

diagram of para substitution and resonance structures stabilising positive charge on ipso carbon

diagram of meta substitution and resonance structures destabilising positive charge on ipso carbon

are halogens activating/deactivating?

what position do they direct?

deactivating

ortho/para directing

para more likely than ortho

why is N activating by resonance while Cl is not (when they are both deactivating by induction)?

N has better orbital overlap than Cl for lone pair donation

why is fluorobenzene more reactive than chlorobenzene?

fluorine lone pairs overlap better with benzene pi system than chlorine lone pairs

• more efficient at electron donation by resonance

what is chemo selectivity?

which functional group in a molecule reacts

how is phenol an ambidentate nucleophile?

it can react at either carbon or oxygen depending on the electrophile

is phenol more or less reactive than benzene?

phenol is much more reactive

phenol + NaOH → ?

phenolate ion + CO₂ → ?

draw resonance structures

what are the two reaction pathways for CO₂ and phenol?

which is faster?

the reaction with the phenolate oxygen is faster

conditions and product of aniline reacting with bromine

0^ºC

aniline and acetic anhydride product

how does the acetylation of amine group on aniline affect electron donation?

reduces electron donation into aromatic ring

how does acetylation of amine group on aniline affect steric hindrance?

creates steric hindrance around ortho position

• double bond is in the same place

how to make monobromine aniline? (hint: with acetylation)

hydrolysis with NaOH

how do deactivating groups affect substitution?

more deactivating groups allows clean mono-substitution

why does the nitration reaction stop at mono-substitution?

B is less reactive than A due to deactivating group

how do activating groups affect substitution?

more activating groups encourage multiple substitutions

how do multiple activating groups affect position?

the strongest activator will determine which position reacts next

alkylation reactions

• what type of groups do they introduce (activating/deactivating)?

• when do they stop?

introduce additional activating groups

alkylations occur until steric factors prevent additional reaction

do acylation reactions favour mono substitution or multiple substitutions?

acyl group deactivates the ring so product is less reactive than reactant

stops at mono substitution

how to do monoalkylation (hint: acylation)?

acylation reaction which stops at monosubstitution

reduce by Clemmensen reduction (Zn/HCl)

why is the carbonyl group deactivating?

conjugation, so pulls electron density out of the ring

which of these rings is more reactive?

which positions are most reactive?

the ring on the right is more reactive

• extra EDG, Me is weakly activating

the most reactive positions are the ortho positions on the right

which ring is most reactive?

although Me is weakly activating, NO₂ is strongly deactivating so the ring on the left is most reactive

where will further nitration take place on this molecule?

on left ring

para position

• least sterically hindered

how to brominate phenol at the meta position?

why is this not usually possible?

hydroxy group is o/p directing so Br won’t go to meta position

use a nitro group as a meta directing deactivator

how to reduce?

diazotisation reactants?

NaNO₂ and HCl

aniline

how is diazotisation reactant formed?

diazotisation mechanism

why does this step happen?

from most electron rich to most electron deficient

what happens when diazonium ion is in conditions above 5ºC?

how does this help Sn1 reactions?

N₂ leaves

leaving empty sp² orbital for nucleophile to attack

diazonium ion + HBF₄ (heat)?

three steps to add amide group?

why would you add an amide group?

1. HNO₃ and H₂SO₄ (nitration)

2. Pd / H₂ (amine)

3. Ac₂O (amide)

stronger ortho/para director so can add another atom at meta to Me position

how to reduce diazonium ion to H atom?

heat above 5 degrees

hypophosphorous acid

reaction for diazonium ion to phenol

heat above 5 degrees

H₂O

diazonium ion reaction with electron rich aromatic mechanism (electrophilic substitution) - using phenol