Organic Chemistry

682 CHAPTER 17 Carbonyl Compounds I

Free energy

Progress of the reaction

TI

TI

Free energy

Progress of the reaction

TI

Free energy

Progress of the reaction

a. b. c.

Figure 17.2

Reaction coordinate diagrams for nucleophilic acyl substitution reactions in which (a) the

nucleophile is a weaker base than the group attached to the acyl group in the reactant,

(b) the nucleophile is a stronger base than the group attached to the acyl group in the

reactant, and (c) the nucleophile and the group attached to the acyl group in the reactant

have similar basicities. TI is the tetrahedral intermediate.

This reaction is called a nucleophilic acyl substitution reactionbecause a nucleo-

phile has replaced the substituent that was attached to the acyl group in the

reactant. It is also called an acyl transfer reactionbecause an acyl group has been

transferred from one group to another.

If the basicities of and are similar, the values of and will be similar.

Therefore, some molecules of the tetrahedral intermediate will expel and others

will expel When the reaction is over, reactant and product will both be present.

The relative amounts of each will depend on the relative basicities of and —that

is, the relative values of and —as well as the relative nucleophilicities of and

—that is, the relative values of and

These three cases are illustrated by the reaction coordinate diagrams shown in

Figure 17.2.

1. If the new group in the tetrahedral intermediate is a weaker base than the group
   that was attached to the acyl group in the reactant, the easier pathway—the lower
   energy hill—is for the tetrahedral intermediate (TI) to expel the newly added
   group and reform the reactants, so no reaction takes place (Figure 17.2a).


2. If the new group in the tetrahedral intermediate is a stronger base than the group
   that was attached to the acyl group in the reactant, the easier pathway is for the
   tetrahedral intermediate to expel the group that was attached to the acyl group in
   the reactant and form a substitution product (Figure 17.2b).


3. If both groups in the tetrahedral intermediate have similar basicities, the tetrahe-
   dral intermediate can expel either group with similar ease. A mixture of reactant
   and substitution product will result (Figure 17.2c).

We can make the following general statement about the reactions of carboxylic acid

derivatives:A carboxylic acid derivative will undergo a nucleophilic acyl substitution

reaction, provided that the newly added group in the tetrahedral intermediate is not a

much weaker base than the group that was attached to the acyl group in the reactant.

C

Y

k 1

k− 1

+ Z−

R

O

C

Z

+ Y−

R

O

C

Z

R Y

k 2

k− 2

−

O

the basicities of

Y−^ and Z− are

similar

Z- k 1 k- 2.

k 2 k- 1 Y-

Y- Z-

Z-.

Y-

Y- Z- k- 1 k 2

(Y-) (Z-)

(Z-) (Y-)

For a carboxylic acid derivative to
undergo a nucleophilic acyl substitution
reaction, the incoming nucleophile must
not be a much weaker base than the
group that is to be replaced.

Tutorial:

Free-energy diagrams for

nucleophilic acyl substitution

reactions