Organic Chemistry

684 CHAPTER 17 Carbonyl Compounds I

reaction to take place. In other words, the reactivity of a carboxylic acid derivative de-

pends on the basicity of the substituent attached to the acyl group: The less basic the

substituent, the more reactive the carboxylic acid derivative.

How does having a weak base attached to the acyl group make the firststep of the

nucleophilic substitution reaction easier? First of all, a weaker base is a more elec-

tronegative base; that is, it is better able to accommodate its negative charge

(Section 1.18). Thus, weaker bases are better at withdrawing electrons inductively

from the carbonyl carbon (Section 1.18); electron withdrawal increases the carbonyl

carbon’s susceptibility to nucleophilic attack.

Second, the weaker the basicity of Y, the smaller is the contribution from the resonance

contributor with a positive charge on Y (Section 17.2); the less the carboxylic acid

derivative is stabilized by electron delocalization, the more reactive it will be.

A weak base attached to the acyl group will also make the secondstep of the nucleo-

philic acyl substitution reaction easier because weak bases are easier to eliminate when

the tetrahedral intermediate collapses.

In Section 17.4 we saw that in a nucleophilic acyl substitution reaction, the nucleo-

phile that forms the tetrahedral intermediate must be a stronger base than the base that

is already there. This means that a carboxylic acid derivative can be converted into a

less reactive carboxylic acid derivative, but not into one that is more reactive. For ex-

ample, an acyl chloride can be converted into an anhydride because a carboxylate ion

is a stronger base than a chloride ion.

the weaker the base, the

easier it is to eliminate

C

Z

R Y

O

−

C

resonance contributors of a carboxylic acid or carboxylic acid derivative

O−

C

RY RY+

O

inductive electron withdrawal by Y increases

C the electrophilicity of the carbonyl carbon

R Y

δ−

δ+

O

O

Cl− <<∼−OCR −OR −OH < −NH 2

relative basicities of the leaving groups

weakest

base

strongest

base

relative reactivities of carboxylic acid derivatives

carboxylic acid

ROH

amide

RNH 2

acyl chloride

>>>∼

acid anhydride

OR

ester

most ROR′

reactive

least

reactive

RCl

C

O

R

C

O

C

O

C

O

C

O

C

O