Organic Chemistry

PROBLEM 16

Write a mechanism for the following reactions:

a. the noncatalyzed hydrolysis of methyl propionate

b. the aminolysis of phenyl formate, using methylamine

PROBLEM 17

a. State three factors that contribute to the fact that the noncatalyzed hydrolysis of an ester

is a slow reaction.

b. Which is faster, hydrolysis of an ester or aminolysis of the same ester?

PROBLEM 18 SOLVED

a. List the following esters in order of decreasing reactivity toward hydrolysis:

b. How would the rate of hydrolysis of the para-methylphenyl ester compare with the rate

of hydrolysis of these three esters?

SOLUTION TO 18a Because the nitro group withdraws electrons from the benzene

ring and the methoxy group donates electrons into the benzene ring, the nitro-substituted

ester will be the most susceptible, and the methoxy-substituted ester the least susceptible,

to nucleophilic attack. We know that electron withdrawal increases acidity and electron do-

nation decreases acidity, so para-nitrophenol is a stronger acid than phenol, which is a

stronger acid than para-methoxyphenol. Therefore, the para-nitrophenoxide ion is the

weakest base and the best leaving group of the three, whereas the para-methoxyphenoxide

ion is the strongest base and the worst leaving group. Thus, both relatively slow steps of the

hydrolysis reaction are fastest for the ester with the electron-withdrawing nitro substituent

and slowest for the ester with the electron-donating methoxy substituent.

SOLUTION TO 18b The methyl substituent donates electrons inductively into the ben-

zene ring, but donates electrons to a lesser extent than does the resonance-donating

methoxy substituent. Therefore, the rate of hydrolysis of the methyl-substituted ester is

slower than the rate of hydrolysis of the unsubstituted ester, but faster than the rate of

hydrolysis of the methoxy-substituted ester.

17.11 Acid-Catalyzed Ester Hydrolysis

We have seen that esters hydrolyze slowly because water is a poor nucleophile and es-

ters have very basic leaving groups. The rate of hydrolysis can be increased by either

acid or When you examine the following mechanisms, notice a feature that

holds for all organic reactions:

1. In an acid-catalyzed reaction, all organic intermediates and products are posi-
   tively charged or neutral; negatively charged organic intermediates and products
   are not formed in acidic solutions.


2. In a reaction in which is used to increase the rate of the reaction, all organic
   intermediates and products are negatively charged or neutral; positively charged
   organic intermediates and products are not formed in basic solutions.

HO-

HO-.

CH 3 C O >

O

CH 3 CO CH 3

O

> CH 3 CO OCH 3

O

NO 2 >>CH 3 C O

O

CH 3 CO

O

CH 3 CO OCH 3

O

CH 3 CNOO 2

O

CH 3 CO

O

CH 3 CO OCH 3

O

692 CHAPTER 17 Carbonyl Compounds I