AROMATIC REACTIONS OF BENZENE

What are the ortho- para- deactivators and hence, meta-directors? Descending order

Electron withdrawing groups:
-N⁺R₃
-NO₂

-CN
-SO₃H

-COCH₃
-COOH

-COOCH₃
-COH

Are halogens deactivators of the benzene ring?

Yes, they are deactivators because they are electron withdrawing groups however they form an additional resonance structure with adds stability to the benzene ring allow for them to be ortho- and para- directors.

What are the ortho- and para- activators of the benzene ring? (ascending order)

Electron Donating Groups (lone-pairs):
-benzene

-CH₃
-NHCOCH₃
-OCH₃

-OH

-NH₂

Clemmensen reduction reagents

Zn(Hg); amalgamated, HCl and heat
NH₂NH₂ (hydrazine), OH^- and heat

(reduces the acyl group to a straight chain)

What can be used to reduce all reactions ?

H₂ ,Pd (hydrogen in palladium) or H₂,Pt (hydrogen in platinum)

For acyl groups to straight chains, deprotect amines, reduce nitro groups and deprotect ethers

Bromination reagents (state effect on the ring)

Br₂ and FeBr₃
OR
Br₂ and AlBr₃ (friedel crafts catalyst)
Bromine is ortho- and para- directing

Chlorination reagents (state effect on the ring)

Cl₂ and FeCl₃
OR
Cl₂ and AlCl₃ (friedel crafts catalyst)
Bromine is ortho- and para- directing

Nitration of Benzene (state the effect on the ring)

HNO₃ and H₂SO₄

Deactivates the ring. Alkylation and Acylation is prevented from taking place.

What are the reagents to synthesise aniline?

1st: Nitration

Reagents: HNO₃ and H₂SO₄
Reduce the Nitro Group
2nd: Add Fe, HCl or SnCl, HCl or H₂/Pt

How to protect and deprotect the amine group of aniline?

Convert the group to an amide by adding an acyl chloride (R-CO-Cl). This amide is activating and also can act as a blocking group. (The NH₂ loses an H to bind and Cl is removed)

To deprotect the amine use aqueous NaOH, H₂O and heat

How to synthesise a aryl diazonium salt?

Use steps to synthesise aniline:
1st: Nitration

Reagents: HNO₃ and H₂SO₄
2nd: Add Fe, HCl

To aniline
Add NaNO₂ (sodium nitrite), HCl at 0^oC
Remember to include counter ion (Cl^-)
This group must be fully converted before any other substituent is added.

What is an azo linkage?

An azo linkage is where the diazonium salt prepared, itself can be used as an electrophile to another benzene ring. It is normally added at the para- position of the ring. If the para- position is taken it is substituted at the ortho- position.

What are the reagents to synthesise a phenol from an aryl diazonium salt?

H₂SO₄ or H₃O⁺, H₂O
-OH is an activating group.

What are the Sandmeyer reactions? (give the reagents and substituent added)

They utilise copper salts (CuX) and enable installation of a halogen or a cyano (CN) group on the ring.

This a way of adding nucleophiles to the benzene ring which is an electron-rich species.

Nucleophiles: ^-CN, Cl^-, Br^- will; replace the diazonium group if appropriate cuprous salt is added to the solution.

CuBr = Br

CuCl = Cl

CuI = I

CuCN = CN

Using phenol, how can this group be converted to an ether (methoxybenzene synthesis)? (protection of the phenol, because phenol can as a weak base)

To protect benzyl bromide (BnBr) and K₂CO₃ can be used to add on O-CH₂-Ph
To convert to a standard ether

NaOH - O^-
then CH₃I is added

To deprotect H₂ Pd/C can be used

How can phenol be used to make an ester?

Acylation using acid anhydrides (RCOOCOR) and base, or acyl chlorides (RCOCL) and base

What is another reagent when added to an aryl diazonium salt would substitute Iodine?

KI

What reagents are used to convert an aryl diazonium salt to flourobenzene?

1.HBF₄

2.Heat

What can be used to convert an aryl diazonium salt to benzene?

H₃PO₂

What are the reagents of sulphonation?

SO₃, H₂SO₄
- SO₃H is a deactivating group and blocking group.

To remove/desulphonate H₂SO₄, H₂O can be used.

What are the reagents for alkylation of an aromatic ring?

RCl and AlCl₃
The substituent is the R group

At the benzylic carbon what reagents and substituents can be added?

1. NBS (N-Bromosuccinimide) + heat

Substitutes and H on the Benzylic carbon to form -CH₂Br (ortho-/para- directing)
Note when performing benzylic reactions, these work best on straight chain alkyl groups
2. Na₂Cr₂O_7, H₂SO₄ and H₂O

Substitutes -COOH in place of the alkyl chain

What are the reagents for acylation?

R-CO-X
X = Cl/Br
and Friedel Craft Catalyst (e.g. AlCl₃)

What is SnAr, Addition-Elimination

This occurs when powerful EW substituents are on the ring.

SNAr results in ipso substitution or bimolecular displacement mechanism , i.e., substitution at an atom that already had a substituent.

What are the considerations for SnAr, Addition-Elimination

In SNAr, the incoming nucleophile must be a stronger base than the substituent that is being replaced, because the weaker of the two bases will be the one eliminated from the

intermediate.

• The electron-withdrawing substituent must be ortho or para to the site of nucleophilic attack because the electrons of the attacking nucleophile can be delocalized onto the substituent only if the substituent is in one of those positions.

Describe the mechanism for SnAr, Addition-Elimination

What is the other type of nucleophilic aromatic substitution than addition-elimination.

Elimination-Addition

What are the two aromatic products that elimination-addition SnAr would give?

Phenol
Reagents: 1. NaOH 2. H₃O⁺
Conditions: 350⁰C

Aniline
Reagents: NaNH₂, NH_3(l) and 2. H₃O⁺

Explain the formation of the benzyne?

Elimination-addition involves the formation of an interesting intermediate called a benzyne.

The amide (base) abstracts an o-proton that triggers the elimination of Cl^-.

The third bond in the benzyne is due to sp2 – sp2 overlap of orbitals which are perpendicular to the π- orbitals of the aromatic ring.

What happens after the formation of benzyne in the elimination-addition mechanism?

• The incoming nucleophile can attack either of the carbons of the “triple bond” of benzyne.

• Protonation of the resulting anion forms the substitution product.

• The overall reaction is an elimination–addition reaction: Benzyne is formed in an elimination reaction and immediately undergoes an addition

reaction.

What is the first step In the diazonium salt formation?

Explain the remainder of the diazonium salt formation after the nitrosonium ion formation