nucleophilic aromatic substitution

S_N1 reactions for benzene

only happens for diazonium salts as this is the only compound with a good enough leaving group (N₂)

shortening of nucleophilic aromatic substitution

S_NAr

when does S_NAr happen

• a good leaving group, eg F^-, Cl^-, Br^- → NEVER H^-

• an ortho or para EWG eg -CF₃, -F, -NO₂

S_N1 for this with nucleophile Nu

S_N2 for benzene rings

NEVER happen

• the σ* orbital is inaccessible inside the benzene ring

• it is impossible to have inversion of the configuration

• S_N2 reactions don’t happen at sp² hybridised carbons

steps in S_NAr

• aromaticity broken first in addition (slow)

• EWG required to stabilise the anionic intermediate

• aromaticity restored in the second step, elimination (fast)

S_NAr for this with nucleophile Nu

why is an o/p EWG needed

• for o/p, anionic intermediate can be stabilised by putting the negative charge on the carbon with the EWG

• this does not happen with meta

• this means EWG activate the ring for S_NAr, which is the opposite to S_EAr in which they deactivate the ring, as in S_NAr the ring need to be as electrophilic as possible

what is the best leaving group for S_NAr

fluoride

why is fluoride the best leaving group

• for S_N2, the best LG is the most stable anion (I^- > Br^- > Cl^- > >F^-)

• HX with lowest PK_a is usually best

• for S_NAr this order is reversed:

  • best F^- > > Cl^- & Br^- > I^- worst

• RDS is the addition step that breaks the aromaticity

• the rate of bond cleavage is not important

• fluoride has the best leaving group for S_NAr because it is electronegative and speeds up the RDS

how is sodium amide (formula?) made and what are its properties

NaNH₂

very strong base

made when sodium metal reacts with liquid ammonia

production of benzyne from p-chlorotoluene

p-chlorotoluene and sodium amide

benzyne intermediate → aniline mixture

benzyne vs normal alkynes

• alkynes require linear geometry for effective overlap of two orthogonal (perpendicular) pairs of p-orbital (along the y and z axes)

• as benzyne is a six-membered ring the triple bond is not like normal linear alkynes - the extra pi bond comes from electrons in sp² hybridised orbitals

• benzyne has a low energy LUMO making it reactive to nucleophiles

other way to make benzyne

• make via a diazonium salt

• o-aminobenzoic acid can be converted into a diazonium salt that spontaneously loses carbon dioxide and nitrogen to make benzyne

stability of benzyne

very reactive/unstable