Page 350 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

Scheme 3.3. Summary of Substituent Effects on Carbonyl Substitution Reactions 331

O O – O – O – O SECTION 3.4
k Electronic Substituent
C 1 R C X k 2
R X k –1 R C X R C X k –2 R C Nu Effects on Reaction
Intermediates
Nu Nu Nu
Nu: – TS for TS for
addition elimination

TS for addition TS for elimination
Based on effect of Based on leaving group ability
of X
–X on C O reactivity
– O –
O
R 2 N
NR 2
RO
F, Cl OR

F, Cl
O –
R C X
X
Nu
O –
NR 2
OR
O
F, Cl
R C X

X X
F, Cl F, Cl
OR OR
NR 2 NR 2
O – O –

of the carboxylate starting material and the double negative charge on the tetrahedral
intermediate make the activation energy for the first step very high. Even if the inter-
mediate is formed, the prospective leaving group O 2− is very difficult to eliminate, so
k >k and no substitution is observed.
−1 2
Perhaps it is worth noting in summary that the series can be extended to include
−
X=NH and X=CH . These analogs would be expected to be even less reactive than
−
2
carboxylate toward nucleophilic addition. The latter species is an enolate. We will
learn in Section 7.7 that enolates are reactive nucleophiles. Carboxylate and amide
anions also are nucleophilic. Even amides are somewhat nucleophilic. Going across
−
the periodic table from F to CH , the carbonyl substituent X transforms the carbonyl
2
group from an electrophile to part of an nucleophilic structure in the anionic structures
by increasing electron donation.