Section 16.7 Additional Considerations Regarding Substituent Effects 641Fortunately, the difference in the physical properties of the ortho- and para-substi-
tuted isomers is sufficient to allow them to be easily separated. Consequently, elec-
trophilic aromatic substitution reactions that lead to both ortho and para isomers are
useful in synthetic schemes because the desired product can be easily separated from
the reaction mixture.
16.7 Additional Considerations Regarding
Substituent Effects
It is important to know whether a substituent is activating or deactivating in determin-
ing the conditions needed to carry out a reaction. For example, methoxy and hydroxy
substituents are so strongly activating that halogenation is carried out without the
Lewis acid ( or ) catalyst.
If the Lewis acid catalyst and excess bromine are used, the tribromide is obtained.
All Friedel–Crafts reactions require the Lewis acid catalyst. However, if there is a
meta director on the ring (remember that all meta directors are moderate or strong
deactivators), the ring will be too unreactive to undergo either Friedel–Crafts acylation
or Friedel–Crafts alkylation.
SO 3 Hbenzenesulfonic
acid+CH 3 CClno reactionOAlCl 3NO 2nitrobenzene+CH 3 CH 2 Clno reactionAlCl 32,4,6-tribromoanisoleanisole+ 3 Br 2OCH 3 OCH 3
Br BrBrFeBr 3p-bromoanisoleanisole o-bromoanisole++Br 2OCH 3 OCH 3 OCH 3
BrBrFeBr 3 FeCl 3A benzene ring with a meta director
cannot undergo a Friedel–Crafts
reaction.82%
p-tert-butylnitrobenzene18%
o-tert-butylnitrobenzenetert-butylbenzene
H 2 SO 4
++HNO 3C(CH 3 ) 3 C(CH 3 ) 3 C(CH 3 ) 3
NO 2NO 2