22. Carboxylic Acid Derivatives: NAS

b. Rank the same esters from most reactive to least reactive in the second slow step of a nucleophilic acyl substitution reaction (collapse of the tetrahedral intermediate).

In each part, rank the compounds in order of increasing rate of nucleophilic attack at C=O by a strong nucleophile like methoxide.

(a)

Show how you would convert 2-methylcyclopentanol to the following products. Any of these products may be used as the reactant in any subsequent part of this problem.

(g) 2-methylcyclopentyl acetate

(h) 1-bromo-1-methylcyclopentane

Predict the product of the multistep synthesis reaction shown.

Predict the product of the following reaction sequences.

(a)

How can the following compounds be prepared from the given starting materials?

a.

Show how you would synthesize each compound, starting with an ester containing no more than eight carbon atoms. Any other necessary reagents may be used.

(a) Ph₃C–OH

(b) (PhCH₂)₂CHOH

(c) PhCONHCH₂CH₃

Show how to synthesize the following amines from the indicated starting materials by acylation–reduction.

(a) N-butylpiperidine from piperidine

(b) N-benzylaniline from aniline

Which compound forms an anhydride more rapidly?

b. What is the product of the reaction of acetamide with HO⁻? The pK_a of NH₃ is 36; the pK_a of H₂O is 15.7.

What is the product of an acyl substitution reaction—a new carboxylic acid derivative, a mixture of two ­carboxylic acid derivatives, or no reaction—if the new group in the tetrahedral intermediate is the following? a. a stronger base than the substituent that is attached to the acyl group

What is the product of an acyl substitution reaction—a new carboxylic acid derivative, a mixture of two ­carboxylic acid derivatives, or no reaction—if the new group in the tetrahedral intermediate is the following? b. a weaker base than the substituent that is attached to the acyl group

Using the pK_a values listed in [TABLE 15.1], predict the products of the following reactions:

c.

Using the pKa values listed in [TABLE 15.1], predict the products of the following reactions:

d.

Starting with acetyl chloride, what neutral nucleophile would you use to synthesize each of the following compounds?

c.