Chapter 18: Aromatic Substitution Reactions Flashcards
Sigma complex
Positively charged, 3 resonant structure intermediate generated in an EAS reaction
Bromination of benzene
Reagents
- Br2
- FeBr3 (iron tribromide) or AlBr3 (aluminum tribromide)
Mechanism
Forms via a sigma complex intermediate and subsequent rearomatization of the benzene ring
Chloronation of benzene
Reagents
- Cl2
- FeCl3 (iron trichloride) or AlCl3 (aluminum trichloride)
Mechanism
Forms via a sigma complex intermediate and subsequent rearomatization of the benzene ring
Sulfonation of benzene
Reagents
Fuming H2SO4
H2SO4 & SO3 (sulfur trioxide)
Mechanism
Forms via a sigma complex intermediate and subsequent rearomatization of the benzene ring
Sulfonation is reversible because the reagent is concentration dependent
Nitration of benzene
Installation of a nitro group
Mechanism
HNO3 (nitric acid) & H2SO4
Mechanism
Sulfuric acid protonates nitric acid and subsequently forms a nitronium ion which performs the nucleophilic attack
Nitration subsequently occurs via the formation of a sigma complex intermediate and subsequent rearomatization of the benzene ring
Nitration of benzene
Installation of an amine group
Reagents
- HNO3 (nitric acid) & H2SO4
- Fe or Zn & HCl
- NaOH
Mechanism
Sulfuric acid protonates nitric acid and subsequently forms a nitronium ion which performs the nucleophilic attack
Nitration subsequently occurs via the formation of a sigma complex intermediate and subsequent rearomatization of the benzene ring
Upon treatment with a metal (Fe or Zn) and HCl the nitro group can be reduced resulting in an ammonium ion (RNH3+) that is subsequently deprotonated by a base
Friedel-Crafts alkylation
Reagents
AlCl3 (aluminum trichloride) & alkyl halide
- Secondary and tertiary alkyl halides are readily converted to carbocations but NOT primary halides EXCEPT ethyl chloride
- Alkyl halide α-carbon must be sp3 hybridized
- Beware of possible rearrangements that may occur
Mechanism
The catalyst (AlCl3) converts the alkyl halide into a carbocation; creating a better electrophile
Alkylation subsequently occurs via the formation of a sigma complex intermediate and subsequent rearomatization of the benzene ring
DEACTIVATED rings CANNOT undergo Friedel-Crafts alkylation
Friedel-Crafts acylation
Mechanism
AlCl3 (aluminum trichloride) & acyl halide
Mechanism
Treatment of the acyl halide with AlCl3 forms a cationic species called an acylium ion
Acylation subsequently occurs via the formation of a sigma complex intermediate and subsequent rearomatization of the benzene ring
Friedel-Crafts acylation
Installing alkyl groups that are prone to rearrangement
Mechanism
- AlCl3 (aluminum trichloride) & acyl halide
- Zn(Hg) (amalgamated zinc) & HCl, heat
Mechanism
Treatment of the acyl halide with AlCl3 forms a cationic species called an acylium ion
Acylation subsequently occurs via the formation of a sigma complex intermediate and subsequent rearomatization of the benzene ring
A Clemmensen reduction can subsequently be employed to recude the aryl ketone to an alkyl group
Strong activating groups
ortho-para directors
Moderate activating groups
ortho-para directors
Weak activating groups
ortho-para directors
Weak deactivating groups
ortho-para directors
Moderate deactivating groups
meta directors
Strong deactivating groups
meta directors
Strong activator
ortho-para director
Strong activator
ortho-para director
Strong activator
ortho-para director
Strong activator
ortho-para director
Strong activator
ortho-para director
Moderate activator
ortho-para director
Moderate activator
ortho-para director
Moderate activator
ortho-para director
Moderate activator
ortho-para director
Weak activator
ortho-para director
Weak deactivator
ortho-para director
Moderate deactivator
meta director
Moderate deactivator
meta director
Moderate deactivator
meta director
Moderate deactivator
meta director
Moderate deactivator
meta director
Moderate deactivator
meta director
Moderate deactivator
meta director
Strong deactivator
meta director
Strong deactivator
meta director
Strong deactivator
meta director
Identifying directing effects for di- and poly-substituted benzene rings
- Identify each group
- Select the most powerful activator and identify where it is directing to
- Identify the unoccupied position as the most likely site for EAS
- Consider steric effects; identify least sterically hindered location
Nucleophilic aromatic substitution
Reagents
- Strong Nuc, 70° C
- H3O+
Mechanism
Benzene ring is attacked by a strong nucleophile which creates a resonance-stabilized intermediate called a Meisenheimer complex that exhibits a negative charge throughout the ring
Criteria for reaction to proceed
- Ring must contain a strong electron-withdrawling group; typically a nitro group
- Ring must contain a good leaving group; typically a halogen
- The leaving group must be either ortho or para to the strong deactivating group
Elimination-addition reactions
Reagents
- NaNH2 (sodium amide), NH3 (l)
- H3O+
Mechanism
Elimination-addition reaction occurs through a high energy radical/alkyne intermediate called a benzyne
Determining reaction type between:
- EAS
- SNAr
- Elimination-addition
