Problem Set on Carboxylic Acid Derivatives: 6.

2-propenamide
Nucleophilic Acyl Substitution Reactions Answer:
O
Provide IUPAC names for each of the following structures:
H2C CH C NH2
O
1. 7. 3,4,5-trimethoxybenzoyl chloride
H2N COCH2CH3 benzocaine

Answer: H3CO
Answer:Ethyl p-aminobenzoate O

H3CO C Cl
O O
2.
H3CO
O
8. acetic formic anhydride

Answer:bis(2-methylpropanoic) anhydride Answer: H O CH3

O
O O
CH2C OCH3

3. 9. N,N-dimethylformamide
Answer:
CH3
Answer:methyl phenylacetate H N
CH3
H3C H
4. 10. O
C C Answer: methyl cis-3-ethylcyclobutanecarboxylate
H C O
O
Cl
C
Answer:trans-2-butenoyl chloride OCH3
O
5.
NH C CH2CH(CH3)2 CH3CH2

11. (E)-2,4-dimethyl-2-hexenoyl chloride

Answer: CH3
Answer:N-cyclopentyl-3-methylbutanamide
CH3CH2CH CH3
C C
H C O
Cl
12. What is the correct structure for phenylbenzoate? group decreases the polarization of the carbonyl by donating electrons to it through the
aromatic ring.
Answer:a O O
a. C O b. H3C C O 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.

What is the order of decreasing

O reactivity towards nucleophilic acyl substitution
O for the O _ .. O
carboxylic acid
c. derivatives?
C (most
O CHreactive first) d. CH O C CH : OH .. _
3 2 2
H3C C NH2 .. H3C C O : + NH3
..
O O O O O H2O
13. Answer:
H3C C O C CH3 H3C C N(CH3)2 H3C C OCH3 (CH3)2CH C OCH3
.. _
I II III IV : O:
O _ .. O
Answer:b. I, III, IV, II : OH _
H3C C NH2 .. H3C C : NH2
H3C C O H
H2O OH
H2N
O O O O O
14.
R C O C R R C NH2 R C OR R C Cl
O
I II III IV .. _
H3C C O : + NH3
Answer:d. IV, I, III, II ..
Consider the reaction below to answer the following questions:
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 O O
structures.
CH3CH2 C Cl + 2 CH2N2 CH3CH2 C CHN2 + CH3Cl + N2
O O O

N COCH2CH3 H3CO COCH2CH3

+
_
O 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.
versus
_O O O
+ _ 17. Diazomethane is an example of a dipolar molecule; a molecule which is neutral overall
+N + COCH2CH3 H3CO .. COCH2CH3 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
O
formal charges.
_
Answer:In general, any factor that makes the carbonyl carbon more polarized will increase +
H C N N
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 H
difference. The electron-withdrawing nitro group increases the polarization of the carbonyl Answer:
by withdrawing electrons from it through the aromatic ring. The electron donating methoxy _ _
+ +
H C N N H C N N

H H
 20. This reaction is an example of:
18. 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. Answer:b. an intramolecular nucleophilic acyl substitution reaction
Answer:
21. The purpose of the base catalyst in this reaction is:
_
O O O Answer:c. to convert the alcohol group to an alkoxide anion, which is a better nucleophile
+
CH3CH2 C Cl CH3CH2 C Cl CH3CH2 C CH N N + Cl-
22. The product of this reaction is:
+ H
CH2N N
_
+ _ Answer:a. a lactone
H C N N +
H C N N
H 23. Methyl butanoate has been isolated from pineapple oil and can be prepared by the Fischer
H esterification reaction shown below. Write the complete stepwise mechanism for this
reaction. Show all electron flow with arrows and include all intermediate structures.
O _
+ OH HCl OCH3
+ + CH3OH + H2O
N2 + CH3Cl CH3CH2 C CH N N + CH3 N N

_ O O
Cl Answer:

Consider the reaction below to answer the following questions: H

OCH3
O
O
OH OH
OH
C CH3OH
OEt
NaH O H Cl O O
O + H2 + EtO- H
OH Na+
H

19. Write the complete stepwise mechanism for this reaction. Show intermediate structures H+ transfer
and all electron flow. Answer:
O O H3C
OCH3 O
C C
OEt OEt + H2O OH
_ + H2
O H Na H + -
O Na+ O H CH3OH
O
H

_
O O
OEt

O + EtO- O
24. Write the complete stepwise mechanism for the acid-catalyzed hydrolysis of the O O
following amide to yield mandelic acid. Show all electron flow with arrows and draw the
structures of all intermediate species. C C
OH + CH3OH HCl OCH3 + H2O
OH OH

H OH2
C NH2 + C OH +
+ NH4 A B C
O O
26. The nucleophile in this reaction is ________________.

Answer:B
Answer:
27. Compound C functions as ___________ in this reaction.
OH H
OH OH
+O Answer:c. a catalyst
H
OH2
C NH2 C NH2 C NH2
H OH2 28. Fischer esterification is an example of:
O + O O
+ H H Answer:b. nucleophilic acyl substitution

H+ transfer
29. Write the stepwise mechanism for the Fischer esterification reaction of benzoic acid and
OH OH OH methanol given above. Show all electron flow by using curved arrows, and include all
O H intermediate structures.
C OH C OH +
+ C NH3
NH4 + NH3 Answer:
O O+ O
H H H H
O O+ O

25. The purpose of the acid catalyst in the hydrolysis of an amide is: C C C OH
OH H Cl OH
OCH3
Answer:b. to enhance the electrophilicity of the amide carbonyl carbon +
HOCH3 H

Consider the information below. H+ transfer

H H
The reaction of a carboxylic acid with an alcohol in the presence of acid is termed Fischer O O+ O H
esterification. C C C O+
OCH3 OCH3 H
+ + H2O OCH3
+ H3O
Provide structure(s) for the starting material(s), reagent(s) or the major organic product(s) of 35.
each of the following reactions or sequences of reactions. Show all relevant stereochemistry. O

30. OH
O 1. LiAlH4, ether
O OH
2. H3O+ H3C OH
CH3
1. LiAlH4, ether
2. H3O+
36.
CH3 CH3
C CH2OH O O
O OEt
HCl OH CH3OH
OCH3 +
31. H2O

O O O O
_
O C CH3 ether (CH3)2CH C O C CH3
(CH3)2CH C Cl + 37.
O O

32. (CH3CH2)2CuLi
Cl
CH3 O CH3 O ether, -78o

OH SOCl2 Cl

38.
H H
33.
N N
O O 1. LiAlH4, ether
2. H3O+
CN C
1. (CH3)2CHMgBr, ether
2. H3O+
39.

34. O O
HN(CH3)2
COOH COOH O
Cl N(CH3)2
OH O CCH3 NaOH, H2O
(CH3CO)2O
NaOH, H2O
40. 44.
O O
O O

OH CH3OH OCH3
Cl benzene
HCl AlCl3
OH OH

41.
Choose the best reagent(s) from the list provided below for carrying out the following
O O transformations.
O OH
Cl pyridine N
N 45. _____ C
+ Cl
H

42. Answer:h. 1. 2 PhMgBr, ether

2. H3O+
O
O O

O HO H C C
1. DIBAH, ether Cl
46.
2. H3O+
O
Answer:a. (Ph)2CuLi, ether

O
43.
O O C CH2OH
H H 47. Cl
CH3OH OH
O
OCH3
Answer:d. 1. LiAlH4, THF
H H 2. H3O+
O
O
 O O

C C
48. OCH3 H 52.
Answer:

CH3 CH2CO2CH2CH3
Answer:f. 1. DIBAH, toluene
2. H3O+

NHCH2CH3 NHCH2CH3
49. NBS CH3CH2OH
O HCl

CH2Br CH2COOH
Answer: d. 1. LiAlH4, THF 1. Mg, ether
2. H3O+
2. CO2
Show how you would accomplish each of the following transformations. More than one step 3. H3O+
may be required. Show all reagents and all intermediate structures. 53.
Answer:
50.
O
Answer:
OH COOH
KMnO4 O
200o C
O OH H3O+ COOH O

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

SOCl2 NaBH4, preparations. Propose a synthesis of aklomide starting with toluene. Show all reagents and
ethanol all intermediate structures.
Cl Answer:
CH3
(CH3)2CuLi, ether HNO3 Cl2
H3C H3C NO2 H3C NO2
O H2SO4 FeCl3
O
Cl
KMnO4
H3O+
51.
Answer: O O O
2 NH3 Cl SOCl2
H2N C NO2 C NO2 HOC NO2
O O O
CrO3, H2SO4 CH3OH
Cl Cl Cl
H H2O OH HCl OCH3
55. Ethyl phenylacetate is a pleasant smelling compound used in perfumery. Draw structures
for each of the intermediates in the synthesis of ethyl phenylacetate below. 61. Poly(ethylene terephthalate), PET, is the polymeric material of Mylar® and Dacron®.
What are the monomers from which PET is prepared?
Answer:
O O
MgBr O CH2CH2OH
Br
Mg 1. ( O CH2CH2 O C C )n PET
ether 2. H3O+

Answer:
CrO3, H2SO4
H2O O O

HO C C OH + HOCH2CH2OH
CH2CO2Et CH2CO2H
EtOH
HCl

Refer to the data below to answer the following questions:

Kodel® is a staple and filament fiber prepared from dimethyl terephthalate and 1,4-
cyclohexanedimethanol. Fabric made from Kodel® has good crease resistance.

CO2CH3 CH2OH

CO2CH3 CH2OH

dimethyl terephthalate 1,4-cyclohexanedimethanol

59. Draw the structure of the Kodel® polymer.

Answer:
O O
(O CH2 CH2 O C C )n
60. Kodel® is an example of:

Answer: b. a polyester