Substitution Reactions on Aromatic Compounds | Advanced Organic Chemistry Study Guide (2002) | Complete Test Bank + Rationales

Substitution Reactions
on Aromatic
Compounds
5
Substitution reactions on aromatic compounds are the most important methods
B
for the preparation of aromatic compounds. Synthesizing them from nonaromatic
precursors is considerably less important.Via substitution reactions, electrophiles
and nucleophiles can be introduced into aromatics. A series of mechanisms is
available for this. Those that are discussed in this chapter are listed in Table 5.1.




5.1 Electrophilic Aromatic Substitutions
via Wheland Complexes (“Ar-SE Reactions”)

The electrophilic aromatic substitution via Wheland complexes, or the Ar-SE
B
reaction, is the classical method for functionalizing aromatic compounds. In this
section we will focus on the mechanistic foundations as well as the preparative
possibilities of this process.



5.1.1 Mechanism: Substitution of H vs ipso-Substitution

For an Ar-SE reaction to be able to occur, first the actual electrophile must be
B
pro- duced from the reagent (mixture) used. Then this electrophile initiates the
aromatic substitution. It takes place, independently of the chemical nature of the
electrophile, essentially according to a two-step mechanism (Figure 5.1). A third
step, namely, the initial formation of a p complex from the electrophile and the
substrate, is generally of minor importance for understanding the reaction event.
In the first step of the actual Ar-SE reaction, a substituted cyclohexadienyl
cation is formed from the electrophile and the aromatic compound. This cation
and its deriva- tives are generally referred to as a s or Wheland complex. Wheland
complexes are de- scribed in the language of the VB method by superpositioning
mentally at least three carbenium ion resonance forms (Figure 5.1). In the
following, these resonance forms are referred to briefly as “sextet formulas.” There
is an additional resonance form for each substituent, which can stabilize the
positive charge of the Wheland complex by a

, M effect (see Section 5.1.3). This resonance form is an all-octet formula.
Wheland complexes are high-energy intermediates because they do not contain
the conjugated aromatic electron sextet present in the product and in the starting
mate- rial. Consequently, the formation of these complexes is the rate-
determining step of

,
, 170 5 Substitution Reactions on Aromatic Compounds


Table 5.1. Substitution Reactions of Aromatic Compounds: Mechanistic Alternatives*


Section Type of substitution using a benzene derivative as an example Substitution type also Mechanistic
known for designation
naphthalen five-
e membered
ring
aromatic
H E
E
5.1–5.2 Rx Rx yes yes “Classic Ar-SE”


Br E
Mg or Li
5.3.2 Rx or BuLi; E Rx yes yes
Ar-SE via
organometallic
H compounds
E
sec-BuLi;
5.3.1 yes yes
Rx E Rx
MDG MDG

B(OR)2 E The same;
E , cat. also
5.3.3/13.3.2 Rx Rx yes yes
Pd(PPh3)4 transition
metal-mediated
N
N Nu
Nu
5.4 Rx Rx yes no

Ar-SN1
Nu /Cu(I) yes no

Hal Nu
Nu Ar-SN via
5.5 EWG EWG yes no Meisenheimer
complexes
yes no Ar-SN of the
Hal Nu Ullmann type
Nu /Cu(I) or
Rx Rx yes yes Transition
13.1–13.3 Nu /Pd(0) metal- mediated
coupling
Nu
Nu
5.6 Rx + Rx yes no Ar-SN via arynes
Nu

*MDG, metallation-directing group; EWG, electron-withdrawing group.