Homework Chapter 21Carboxylic Acid Derivatives: Nucleophilic Acyl

Substitution Reactions mandatory problems are highlighted (up to

page 16)
SHORT ANSWER
IUPAC Naming Instructions: Provide proper IUPAC names.
1.

Name:

ANS:
Ethyl p-aminobenzoate
2.

Name:

ANS:
bis(2-methylpropanoic) anhydride

3.

Name:

ANS:
methyl phenylacetate
4.

Name:

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

ANS:
trans-2-butenoyl chloride
5.

Name:

ANS:
N-cyclopentyl-3-methylbutanamide
Drawing Instructions: Draw structures corresponding to each of the given names.
6.

Draw: 2-propenamide

ANS:

7.

Draw: 3,4,5-trimethoxybenzoyl chloride

ANS:

8.
ANS:

Draw: acetic formic anhydride

Chapter 21

9.

Draw: N,N-dimethylformamide

ANS:

10.

Draw: methyl cis-3-ethylcyclobutanecarboxylate

ANS:

11.

Draw: (E)-2,4-dimethyl-2-hexenoyl chloride

ANS:

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

12.

What is the correct structure for phenylbenzoate?

a.

b.

c.

d.

ANS:
a
Exhibit 21-1
What is the order of decreasing reactivity towards nucleophilic acyl substitution for the carboxylic
acid derivatives? (most reactive first)
13.

a.
b.
c.
d.

I, II, III, IV
I, III, IV, II
II, IV, III, I
II, I, III, IV

ANS:
b

14.
a.
b.
c.
d.

I, III, II, IV
II, III, I, IV
III, II, I, IV
IV, I, III, II

ANS:
d

Chapter 21

15.

The ester ethyl p-nitrobenzoate is more reactive towards nucleophilic acyl substitution than
ethyl p-methyoxybenzoate. Explain this reactivity difference using both words and
structures.

ANS:
In general, any factor that makes the carbonyl carbon more polarized will increase the reactivity of
the carboxylic acid derivative. In these particular examples, both are aromatic ethyl esters. It is the
substituent on the aromatic ring that is affecting the reactivity difference. The electronwithdrawing nitro group increases the polarization of the carbonyl by withdrawing electrons from
it through the aromatic ring. The electron donating methoxy group decreases the polarization of
the carbonyl by donating electrons to it through the aromatic ring.

16.

Write the complete stepwise mechanism for the basic hydrolysis of acetamide, shown below.
Show all electron flow with arrows and draw all intermediate structures.

ANS:

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

Exhibit 21-2
Consider the reaction below to answer the following question(s):

Acid halides react with diazomethane to yield diazoketones. Excess diazomethane is used to
prevent the HCl produced in the reaction from reacting with the diazoketone.
17.

Refer to Exhibit 21-2. Diazomethane is an example of a dipolar molecule; a molecule which

is neutral overall but has charges on individual atoms. One resonance form of diazomethane
is drawn below. Draw the Lewis structure of the other resonance form of diazomethane. Be
sure to include all formal charges.

ANS:

18.

Refer to Exhibit 21-2. The intermediate structures for the mechanism for the reaction of
propanyl chloride with diazomethane are provide below. Show all electron flow with arrows
on these structures.

Chapter 21

ANS:

Exhibit 21-3
Consider the reaction below to answer the following question(s):

19.

Refer to Exhibit 21-3. Write the complete stepwise mechanism for this reaction. Show
intermediate structures and all electron flow with arrows.

ANS:

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

20.

Refer to Exhibit 21-3. This reaction is an example of:

a.
b.
c.
d.

an intermolecular nucleophilic acyl substitution reaction

an intramolecular nucleophilic acyl substitution reaction
an intermolecular SN2 reaction
an intramolecular SN2 reaction

ANS:
b

21.
a.
b.
c.
d.

Refer to Exhibit 21-3. The purpose of the base catalyst in this reaction is:
to polarize the carbonyl group to make it more electrophilic
to convert the ester to an intermediate carboxylic acid
to convert the alcohol group to an alkoxide anion, which is a better nucleophile
all of the above

ANS:
c
22.
a.
b.
c.
d.

Refer to Exhibit 21-3. The product of this reaction is:

a lactone
an anhydride
a lactam
an ether

ANS:
a
23.

Methyl butanoate has been isolated from pineapple oil and can be prepared by the Fischer
esterification reaction shown below. Write the complete stepwise mechanism for this
reaction. Show all electron flow with arrows and include all intermediate structures.

Chapter 21

ANS:

24.

Write the complete stepwise mechanism for the acid-catalyzed hydrolysis of the following
amide to yield mandelic acid. Show all electron flow with arrows and draw the structures of
all intermediate species.

ANS:

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

25.
a.
b.
c.
d.

The purpose of the acid catalyst in the hydrolysis of an amide is:

to enhance the nucleophilicity of the water molecule
to enhance the electrophilicity of the amide carbonyl carbon
to enhance the electrophilicity of the water molecule
to shift the equilibrium of the reaction

ANS:
b
Exhibit 21-4
Consider the information below to answer the following question(s).
The reaction of a carboxylic acid with an alcohol in the presence of acid is termed Fischer
esterification.

26.

Refer to Exhibit 21-4. The nucleophile in this reaction is _____.

ANS:
B
27.
a.
b.
c.
d.

Refer to Exhibit 21-4. Compound C functions as _____ in this reaction.

a base scavenger
a solvent
a catalyst
a neutralizer

ANS:
c

28.
a.
b.
c.
d.

Refer to Exhibit 21-4. Fischer esterification is an example of:

nucleophilic acyl addition
nucleophilic acyl substitution
nucleophilic acyl elimination
nucleophilic acyl rearrangement

ANS:
b

10

Chapter 21

29.

Refer to Exhibit 21-4. Write the stepwise mechanism for the Fischer esterification reaction
of benzoic acid and methanol given above. Show all electron flow by using curved arrows,
and include all intermediate structures.

ANS:

Exhibit 21-5
Provide structure(s) for the starting material(s), reagent(s) or the major organic product(s) of each
of the following reactions or sequences of reactions. Show all relevant stereochemistry.

30.
ANS:

11

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

31.
ANS:

32.
ANS:

33.
ANS:

12

Chapter 21

34.
ANS:

35.
ANS:

36.
ANS:

13

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

37.
ANS:

38.
ANS:

39.
ANS:

14

Chapter 21

40.
ANS:

41.
ANS:

42.

15

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

ANS:

43.
ANS:

44.
ANS:

16

Chapter 21

Exhibit 21-6
Choose the best reagent(s) from the list provided below for carrying out the following
transformations. Place the letter corresponding to the best choice in the blank to the left of the
transformation.
a.
b.
c.
d.
e.

(Ph)2CuLi, ether
NaBH4, ethanol
1. CH3MgBr, ether
2. H3O+
1. LiAlH4, THF
2. H3O+
(CH3)2CuLi, ether

45.

f.
g.
h.

1.
2.
1.
2.
1.
2.

DIBAH, toluene
H 3O +
(Ph)2CHMgBr
H 3O +
2 PhMgBr, ether
H 3O +

_____

ANS:
h

46.

_____

ANS:
a

47.

_____

ANS:
d

17

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

48.

_____

ANS:
f

49.

_____

ANS:
d
Exhibit 21-7
Show how you would accomplish each of the following transformations. More than one step may
be required. Show all reagents and all intermediate structures.

50.
ANS:

51.

18

Chapter 21

ANS:

52.
ANS:

53.
ANS:

54.

Aklomide, 2-chloro-4-nitrobenzamide, is an ingredient in veterinary antibacterial

preparations. Propose a synthesis of aklomide starting with toluene. Show all reagents and
all intermediate structures.

19

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

ANS:

55.

20

Ethyl phenylacetate is a pleasant smelling compound used in perfumery. Draw structures for
each of the intermediates in the synthesis of ethyl phenylacetate below.

Chapter 21

ANS:

Exhibit 21-8
For each pair of compounds below, tell which spectroscopic technique you would use to
distinguish between the two members of the pair. Tell what differences you would expect to see.

56.
ANS:
IR

2250 cm 1 (nitrile)

17301760 cm 1
(four-membered lactam)

Although you would not be expected to know the absorption of a four-membered lactam, you
should be able to predict that IR spectroscopy would differentiate these two compounds based
solely on the nitrile absorption in the first compound and the fact that the lactam would have a
carbonyl absorption somewhere in the region of 16601750 cm 1.

57.

21

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

ANS:
IR
1

1735 cm 1
(aliphatic ester)

1720 cm 1
(aromatic ester)

methyl singlet
methylene singlet

one triplet
one quartet

1820, 1760 cm 1
(anhydride)

25003300 cm 1 (acidOH)
17101760 cm 1 (carboxyl)
1715 cm 1 (ketone)

H NMR

58.
ANS:
IR

H NMR

one triplet
one quartet

three overlapping triplets

one quartet
one singlet

Exhibit 21-9
Refer to the data below to answer the following question(s):
Kodel is a staple and filament fiber prepared from dimethyl terephthalate and 1,4cyclohexanedimethanol. Fabric made from Kodel has good crease resistance.

59.
ANS:

22

Refer to Exhibit 21-9. Draw the structure of the Kodel polymer.

Chapter 21

60.
a.
b.
c.
d.

Refer to Exhibit 21-9. Kodel is an example of:

a polyurethane
a polyester
a polyamide
a polycarbonate

ANS:
b

61.

Poly(ethylene terephthalate), PET, is the polymeric material of Mylar and Dacron . What
are the monomers from which PET is prepared?

ANS:

2. Name the following substance. Atoms other than carbon and hydrogen are labeled.

ANS:
4-methylpentanoyl chloride

23

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

63.

Name the following substance. Atoms other than carbon and hydrogen are labeled.

ANS:
ethyl 1-chloropropanoate

MULTIPLE CHOICE
1.
a.
b.
c.
d.

Which of the following will take place via nucleophilic acyl substitution?
thioester producing and acid chloride
ester producing a thioester
ester producing an amide
acid anhydride producing an acid chloride

ANS: C
2.

a.
b.
c.
d.
e.
f.
g.

The following reaction could be classified as which type of nucleophilic acyl substitution?
More than one step might be needed.

amoniolysis
alcoholysis.
reduction.
hydrolysis.
Grignard reaction.
c or e depending on reaction conditions.
The reaction will not occur via nucleophilic acyl substitution.

ANS: D

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Chapter 21

3.

a.
b.
c.
d.
e.
f.
g.

The following reaction could be classified as which type of nucleophilic acyl substitution?
More than one step might be needed.

amoniolysis
alcoholysis.
reduction.
hydrolysis.
Grignard reaction.
c or e depending on reaction conditions.
The reaction will not occur via nucleophilic acyl substitution.

ANS: B
4.

a.
b.
c.
d.
e.
f.
g.

The following reaction could be classified as which type of nucleophilic acyl substitution?
More than one step might be needed.

amoniolysis
alcoholysis.
reduction.
hydrolysis.
Grignard reaction.
c or e depending on the reaction conditions.
The reaction will not occur via nucleophilic acyl substitution.

ANS: C
5.

The following reaction could be classified as which type of nucleophilic acyl substitution?

25

Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

a.
b.
c.
d.
e.
f.
g.

amoniolysis
alcoholysis.
reduction.
hydrolysis.
Grignard reaction.
c or e depending on reaction conditions.
The reaction will not occur via nucleophilic acyl substitution.

ANS: G
6.

What is the product when the following substance reacts with trimethylamine ((CH3)3N)?
Atoms other than carbon and hydrogen are labeled.

a.

b.

c.

d.
No reaction occurs.
ANS: D

26

Chapter 21

7.

a.
b.
c.
d.
e.

What is the name of the product when the following substance reacts with NaCH3COO?
Atoms other than carbon and hydrogen are labeled.

4-methylbutanoic acid
acetic 4-methylbutanoic anhydride
4-methylbutyl acetate
acetyl 4-methylbutanoate
No reaction occurs.

ANS: B
8.

a.
b.
c.
d.
e.

Which line in the following spectrum would indicate the presence of a carbonyl group?

1
2
3
4
5

ANS: E

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Carboxylic Acid Derivatives: Nucleophilic Acyl Substitution Reactions

9.

Based on the following spectrum

the sample used would probably be classified as a(n):

a. aldehyde.
b. ketone.
c. ester.
d. The spectrum is not specific enough to classify the substance.
ANS: C
10.

The following is an excerpt from a spectrum taken on an unknown sample.

To which of the following functional groups might the unknown belong?

a. amide
b. acid chloride
c. carboxylic acid
d. ester
e. None of these can be eliminated.
ANS: D

28

Chapter 21

11.

Consider the following molecular model. Atoms other than carbon and hydrogen are
labeled.

Which of the following reactants could be used to produce this compound?

a. 1-chloropropanoic acid and ethanol
b. propanoic acid and chloroethanol
c. propanoic acid and ethanol
ANS: A
12.

Consider the structure given below which might be found in a protein.

Which of the following is not applicable to this structure?

a. contains three monomers
b. contains amide bonds
c. formed from a diacid and diamine
d. contains three types of monomers
e. All of these apply to this structure.
ANS: C
13.
a.
b.
c.
d.

Which of the following describes nucleophilic acyl substitution?

Nucleophile adds to the electrophilic carbon of the carbonyl bond.
Electrophile replaces a group on the carbon alpha to the carbonyl.
Nucleophile replaces a group adjacent to the carbon of carbonyl.
Two carbonyl groups react with each other.

ANS: C

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