L Le ev ve el l 3 3 – – C Ca as se e 3 36 6
V Vi ic ca ar ri io ou us s N Nu uc cl le eo op ph hi il li ic c S Su ub bs st ti it tu ut ti io on n
K Ke ey y p po oi in nt t: : C Ch Ch Ch Ch C C a an ng ge e i in i in in in i i t th t th th th th t t e e r ra ra r ra ra ra ra r rat te te t te te te te t te- -d de de d de de de d det te te t te te te te t ter rm r rm rm rm
rm r r i in i in in in i i i
in i in in in i i g g s st te te t te te te te t tep ep ep p
O 2 N
EWG
R
X
O 2 N
EWG
R
V Vi ic ca ar ri io ou us s N Nu uc cl le eo op ph hi il li ic c S Su ub bs st ti it tu ut ti io on n
The alkylation of aromatic nitro compounds by carbanions having a leaving group
at the nucleophilic center is called Vicarious Nucleophilic Substitution of Hydrogen (VNS) (Scheme 36.1). This reaction is one of the scarce general processes that
result in the formal nucleophilic aromatic substitution of hydrogen.
O 2 N
EWG
R
X
O 2 N
EWG
R
EWG = electron-withdrawing group
X = leaving group
Scheme 36.1
The reaction proceeds by addition of the nucleophile to the ortho- or para-position of the nitroarene and subsequent base-promoted E-elimination of XH from the
intermediate V-adduct 1. The VNS reaction is very general and the ortho/para regioselectivity is controlled by steric factors. Tertiary carbanions replace hydrogen
in the VNS reaction exclusively in the para-position (Scheme 36.2).
NO 2
EWG
R
X
N
O
O
H
EWG
X
R
N
O
O
EWG
R
H 3 O
+
NO 2
EWG
R
k 1
k -1
k k
k 2
k k
base
1
2
–XH
Scheme 36.2