22. Carboxylic Acid Derivatives: NAS

Show the mechanism for the acid-catalyzed formation of 23c starting with the product obtained from its hydrolysis.

Aspartame, the sweetener used in the commercial products NutraSweet and Equal, is 200 times sweeter than sucrose. What products will be obtained if aspartame is hydrolyzed completely in an aqueous solution of HCl?

What products are formed from the acid-catalyzed hydrolysis of the following esters?

a.

b.

Using the mechanism for the acid-catalyzed hydrolysis of an ester as your guide, write the mechanism—showing all the curved arrows—for the acid-catalyzed reaction of acetic acid and methanol to form methyl acetate. Use HB⁺ and :B to represent the proton-donating and proton-removing species, respectively.

In the mechanism for the acid-catalyzed hydrolysis of an ester,

c. what species is HB⁺ most likely to be in the hydrolysis reaction?

d. what species is HB⁺ most likely to be in the reverse reaction?

a. When a carboxylic acid is dissolved in isotopically labeled water (H₂O¹⁸) and an acid catalyst is added, the label is incorporated into both oxygens of the acid. Propose a mechanism to account for this.

c. If an ester is dissolved in isotopically labeled water (H₂O¹⁸) and an acid catalyst is added, where will the label reside in the product?

Show how you would accomplish the following syntheses.

c. hexan-1-ol → 2-hydroxyheptanoic acid

Predict the products and propose mechanisms for the following reactions.

(a)

Suppose we have some optically pure (R)-2-butyl acetate that has been "labeled" with the heavy ¹⁸O isotope at one oxygen atom as shown.

(b) Repeat part (a) for the acid-catalyzed hydrolysis of this compound.

Propose a mechanism for the acid-catalyzed hydrolysis of phenylalanine ethyl ester.

The Reformatsky reaction is an addition reaction in which an organozinc reagent is used instead of a Grignard reagent to add to the carbonyl group of an aldehyde or a ketone. Because the organozinc reagent is less reactive than a Grignard reagent, a nucleophilic addition to the ester group does not occur.

The organozinc reagent is prepared by treating an α-bromo ester with zinc.

Describe how each of the following compounds can be prepared, using a Reformatsky reaction:

c.

Propose mechanisms for the following reactions.

(c)

Propose mechanisms for the following reactions.

(d)

The mechanism for acidic hydrolysis of a nitrile resembles the basic hydrolysis, except that the nitrile is first protonated, activating it toward attack by a weak nucleophile (water). Under acidic conditions, the proton transfer (tautomerism) involves protonation on nitrogen followed by deprotonation on oxygen. Propose a mechanism for the acid-catalyzed hydrolysis of benzonitrile to benzamide.

Compare each of the mechanisms listed here with the mechanism for each of the two parts of the acid-catalyzed hydrolysis of an ester, indicating a. similarities. b. differences.

4. acid-catalyzed hydrolysis of an amide