Synthesis Topic 4

Question 1

When we react benzene with Br₂ why we use Lewis acid in this reaction?

Answer 1

Benzene is not very reactive, we need stronger electrophile so we activate Br₂ with reaction with Lewis acid.

Question 2

What is Wheland intermediate?

Answer 2

The intermediate formed in electrophilic aromatic substitution is a stabilised cation called Wheland intermediate.

Question 3

What stabilises Wheland intermediate?

Answer 3

Resonance of positive charge

Question 4

What are typical conditions of benzene nitration?

Answer 4

Concentrated HNO₃ and concentrated H₂SO₄ 1:1

Question 5

What are two steps of benzene nitration?

Answer 5

Generation of the electrophile

Electrophilic aromatic substitution

Question 6

What is the reaction between HNO₃ and H₂SO₄?

Answer 6

Nitric acid protonated, water remoes and nitronium ion formed.

Question 7

What are typical conditions for benzene sulfonylation?

Answer 7

Concentrated H₂SO₄ saturated wit SO₃ (oleum)

Question 8

What are two steps of aromatic ring sulfonation?

Answer 8

Generation of electrophile

Electrophilic aromatic substitution

Question 9

What is reaction of benzene sulfonation?

Answer 9

Sulfuric acid is protonated, water removed and sulfonium ion formed. π cloud in benzene attacks sulfonium ion breaking S=O bond, Wheland intermediate is formed and proton eliminated to form double bond and neutralise positive charge.

Question 10

What are typical Lewis acids used in The Friedel Crafts reaction?

Answer 10

FeCl₃, FeBr₃, AlCl₃

Question 11

What are typical conditions for Alkylation of aromatic ring? (The Friedel-Crafts reaction)

Answer 11

R-Cl group and Lewis acid

Question 12

What is the reaction of benzene alkylation?

Answer 12

R-Cl reacts with Lewis acid. Lewis acid has an empty p orbital that acepts an electron ang carbocation is formed. π system attacks carbocation borming new C-C bond and forming Wheland intermediate. Proton is used to form double bond and regain aromaticity

Question 13

Why in Friedel Craft reaction over alkylation can occur?

Answer 13

The products of the reaction is more reactive than the starting materials because alkyl groups are electron donating.

Question 14

Why Friedel-Crafts alkylation is only useful with tertiary alkyl halide electrophiles?

Answer 14

Because rearangment occurs with secondary alkyl halides and two products will form. Because primary carbocation will move positive chage to midle carbon to form more stable secondary carbocation.

Question 15

How do we convert benzene to n-propylbenzene?

Answer 15

By making a ketone via Friedel-Crafts acylation and then reduce the alkane.

Question 16

What is the reaction of Friedel-Crafts benzene acylation?

Answer 16

Acyl chloride reacts with Lewis acid forming one complex. Leaving group leaves forming acylium cation. π system attack acylium cation forming Wheland intermediate. Proton used to regenerate aromaticity.

Question 17

Why Friedel-Crafts acylation is more reliable than alkylation?

Answer 17

Because no rearrangments of cation occur and product has electron withdrawing substituent meaning electron dencity is lower and product is less reactive than starting materials meaning no over-acylation.

Question 18

Answer 18

We have 3 different H environments so we add just one NO₂. We see that 2 H has J=10Hz meaning ortho position and two has J=2Hz meaning meta position. The H with highest shemical shift is closest to electron withdrawing NO₂. So we have two H with high chemical shoft next to NO₂ and one furter away.

Question 19

How does the rate of electrophilic aromatic substitution changes when we have electron rich substituent?

Answer 19

Electron rich aromatics are more nucleophilic and react faster in electrophilic aromatic substitution reaction.

Question 20

How does the rate of electrophilic aromatic substitution changes when we have electron poor substituent?

Answer 20

Electron poor aromatics are less ncleophilic and react slower.

Question 21

How methyl group substituent in benzene ring affects nitration reaction?

Answer 21

Molecule is nitrated faster because methyl group has weak inductive effect and also donates electrons by hyperconjugation

Question 22

How phenol group substituent in benzene ring affects nitration reaction?

Answer 22

Phenol reacts much faster than benzene as a result of mesometric effect is stronger than inductive effect. Lone pair from O can be delocalized into aromatic group.

Question 23

How nitro (NO₂) group substituent in benzene ring affects nitration reaction?

Answer 23

Nitrobenzene react much slower than benzene as a result of the nitro group is mesomerically (N in NO₂ is positive) and inductively (N more electronegative than C) electron withdrawing.

Question 24

Why para is the most common substuent location and meta least common substituent position in benzene with electron donating group?

Answer 24

Because para and ortho forms intermediate that is more stable as a result of having more resonance forms (4) and meta has less resonance forms (3).

Question 25

Why para position is more common than ortho in benzene with electron donating group?

Answer 25

Para position is less stericaly hinded as large groups are further away.

Question 26

What is kinetic control of substitution reaction?

Answer 26

Fastest products (lowest energy TS) formed predominates.

Question 27

Why anisole reacts faster than benzene?

Answer 27

Because more electron density at ortho and para positions, meaning smaller E_a of transition state

Question 28

Why meta is the most common position for substituent in benzene with electron withdrawing group?

Answer 28

Because intermediate is more stable as it has least electron density withdrawing from carbocationic intermediate. Ortho and para positions has resonance forms with positive charge near N group. As a result we have positive carbon near electron withdrawing group, this is very unstable.

Question 29

What is the efect of halogen substituent for benzene reactions?

Answer 29

Halogens are inductively electron withdrawing but they are also mesomerically electron withdrawing. However, mesomeric effect in halobenzenes is very weak. Thus it controls o/p-selectivity, but does not have great influence on reaction rate.

Question 30

How can you decrease over-substitution while not changing reaction?

Answer 30

By diluting acids