Chapter 17 Reactions of Aromatic Compounds

Electrophilic Aromatic Substitution (EAS)

When an aromatic ring reacts with a base with a negative charge to gain an electrophile (stays aromatic)

• loses aromaticity during the intermediate cation, but the product is aromatic 

  • carbocation intermediate/sigma complex is resonance stabilized

• can be any aromatic ring, not only benzene

Benzene Bromination (EAS)

Benzene + FeBr3 —> carbocation/sigma complex —> deprotonated by FeBr4 to gain bromobenzene

Iodination of Toluene or Benzene (EAS)

Iodine (I) + Nitric acid (HNO3) react with toluene replacing H with I

• to start the reaction iodine must react with HNO3 to form I+ that reacts with the benzene

• carbocation intermediates / sigma complexes that are resoancne stabalized

• deprotonation by h20

• EAS

• creates iodobenzene

Benzene Chlorination (EAS)

Aluminum chloride (AlCl3) + Cl2 —> creates AlCl5 reagent

Benzene + AlCl5 reagent —> sigma complexes with carbocation —> deprotonated by Cl- —> chlorobenzene formed

Activating groups

They are electron donating groups that help direct the substitution mechanism

Ortho and Para directing substitutents that are activating groups

Alkyl (R), Alkoxy (RO), and Amine Groups (NH2)

• R: push induction for stable carbocation

• RO: does resonance stabilization of sigma complex

• NH2: does resonance stabilization of sigma complex

  • (NOTE THAT R IS JUST CARBON CHAINS EX METHANE, EHTANE, ETC.)

They all direct in favor ortho and para positions that have stable tertiary carbocation

Order of ortho and para directing substituents

Remember the groups: O > NR2 > OH > OR > NHCOR > R

Deactivating groups

They are electron-withdrawing groups substituents that push for the meta position product

Meta-Directing Substituents

The deactivating groups (electron withdrawing) push for meta attacks 

• MOST COMMONLY USED IS NO2

Seperate by carbonyl groups: COOH, COOR, COR, CRR

And others: NO2, CN, SO3H, N+R3

Halobenzenes

Refers to benzene attached to any halogen (Br, F, I, Cl)

They are electron-withdrawing groups (meta?) but halogens have lone pairs (ortho/para?) 

• lone pairs resonance stabalize sigma complex

• halogens electron withdrawing deactivates the benzene (less reactive)

• their net effect cancels out so they are ORTHO AND PARA DIRECTING

Ortho and para: resonance stabalized by charged

Meta: pos charge placed on halogen’s carbon —> unstable

Multiple Substituents (ortho and para activators vs meta activators)

Ortho & para activators take priority over meta activators

• Strong ortho & para activators: NH2> OH > OR

• Moderate ortho & para activators: R (alkyl) > Halogens

• Meta Directors: NO2, CN, Ket & alde, etc.

  • meta directors have the smallest effect

Multiple Substituents of the same type of activtor and strength

If a benzene has 2 substituents that are both activating or both deactivating and they want the new group to be attached to different reaction sites —> it produces mixed products

• same class activator or deactivator on benzene —> mixed products

  

Multiple Substituents Reinforcing vs Opposing

• Reinforcing positions → product is obvious

  • if the original structure has substituents that push new group to the same type of reaction site (same products)

    

• Opposing → strong activator wins

  • if the original structure substituents direct a new group to different type of reaction sites (the product enforced by the storngest activator wins)

Friedel-Crafts Alkylation

Sec or Tert alkyl halide + AlCl3 or FeCl3 —> alkyl carbocation —> Benxene + alkyl carbocation —> sigma complex resonance stabalized —>  alkylbenzene

Friedal-Crafts Alkylation Carbocation Sources

Carbocation can form from 4 things

• R-X + AlCl3 —> R+ + x-AlCl3

• R-X + FeCl3 —> R+ + x-FeCl3

Alkene + HF —> Protonated Alkene + F-

Alcohol + BF3 —> Carbocation +OHBF3

Friedel-Crafts Alkylation Limitations

1. Only works on reactive rings (benzene, benzenes with electron donating groups, & halobenzenes)

   1. CANNOT WORK WITH STRONGLY DEACTIVATING SUBSTITUENTS (benzens with electron withdrawing groups)

2. Carbocation rearrangements are possible —> more stable carbocation that changes the final product

3. The alkyl groups can activate the ring, resulting in multiple alkylations

Reactive ring dependent, carbocation rearrangements, multiple alkylations

Friedel Crafts Acylation

Acylbenzene is formed

• carboxycylic acid + socl2 —> +alcl3 → r-c=o +alcl4

• r-c=o + benzene ring —> sigma complex —> +alcl4 —> acylebenzene

Rules for Friedel-Crafts acylation

Only reacts with benzene, benzenes with electron donating groups, and halobenzenes

• CANNOT REACT WITH STRONG DEACTIVE SUBSTITUENTS (electron-withdrawing groups or meta position drivers)

Favors Para substitutions

• ortho possible but it has steric hinderence

Clemmensen Reduction

Reducing an acylbenzene to an alkylbenzene

• reduced using zincmercury and HCl

  

Gatterman-Koch Formylation

Like acylation but instead of using r-c=o it uses h-c=o

• produces a benzaldehyde

  

Nucleophilic Aromatic Substitution

When a nucleophile replaces a benzene with 2 substitutents (strong electron withdrawing group and a leaving group

• this leaving group tends to be a halogen

• the nucleophile attacks the ring at the halogen site, preparing it for nucleophilic substitution

  • where nuc replaces halogen

in nucleophilic substitution, the EWG must be at the ORTHO OR PARA SITE

Addition-Elimination Mechanism

The nucleophilic aromatic substitution that occurs when the structure has 2 STRONG EWG (like 2 NO2’s attached)

• the leaving group must still be either ortho or para (ortho to one ewg and para to the other ewg)

• reacts with a nucleophile that will replace the leaving group halogen

• it is a fast reaction

  

Elimination-Addition (benzene mechanism)

Occurs when a benzene has no strong EWG substituents and only a leaving group

• results in an intermediate benzene and a final product of benzene with a nuc replacing the halogen (still nuc substitution)

Organocuprate Reagents coupling

Requires aryl halide (formed by halobenzene + alkyl halide reacting together)

when an aromatic ring is coupled to an alkyl chain

• First an Aryl Halide + 2 Li —> Aryl Lithium

• Second 2 Aryl Lithium + CuI —> 2 ArylCuLi 

  • This is the gilman reagent or the organocuprate (R2CuLi)

• the reagent + Alkyl Haldie —> Aryl Alkyl final coupling product

Heck Reaction

Aryl halide + alkene —> PdOAc2 catalyst with PPh3 Et3N —> coupled product

Addition Reactions

2 types: benzene chlorination and catalytic hydrogenation

Benzene Chlorination

When bezene treated with excess cl. (3Cl2)

• done under heat and preasure or hv

• producees bezne hexachloride (6 Cl’s attached)

Catalytic Hydrogenation

Benzene reacts with excess hydrogen gas (3 H2)

• done under heat and pressure + catalyst presence (Pt, Pd, Ni, Ru, Rh)

• all carbons hydrogenated, produces cyclohexane

  

Side-Chain Reactions of Benzene

2 types: Permanganate Oxidation and Chlorination

Premanganate Oxidation side chain benzene reaction

alkyl benzene + KMnO4, H20, H+ —> Benzoic acid

• alkylbenzenes is when a benzens has 1 or more alkyl groups attached

Chlorination Side chain free radical halogenation

Done with the goal of replacing the H’s on the benzylic carbon to Cl’s

Bromination

Ethylbenzene reacts with radical bromine —> resonance stabalized —> Br-Br —> Bromoethylbenzene

• radical bromine formed with Br2 or NBS —> Hv —> Br radical

Nucleophilic Substition

Sn1 and Sn2 Reactions

• Sn1 Reaction is carbocation nucleophilic substitution (2 step)

• Sn2 Reaction is simple nucleophilic substitution

Sn1 Reaction with benzene

Benzene + nucleophile & heat —> Benzene carbocation intermediates —> Benzene + nucleophile

• if the original structure is a benzyl halide, it will react  faster than regular alkyl halides

Sn2 Reaction with Benzene

One step simple nucleophilic substitution

• leaving group is replaced by strong non-bulky nuc

Phenol Reactions

2 types: phenol acylation and phenoxide ion formation

Phenol acylation: phenol reacts with acetic acid, producing esters

Phenoxide ion formation: Phenol reacts with NaOH to give phenoxide ions

Phenol Electrophilic Aromatic Substitution

Phenol —NaOH, H20 —> Phenoxide Ion Formed —> +Br2 —> sigma complex —> 2 Br2 —> tribromo phenol

• ortho and para directing