Chapter 24—Amines and Heterocycles
SHORT ANSWER
Exhibit 24-1
Classify each of the following nitrogen atoms in the following compounds as primary, secondary,
tertiary, or quaternary.
1.
ANS:
The nitrogen atom in ephedrine is secondary.
2.
ANS:
The nitrogen atom in amphetamine is primary.
3.
ANS:
The nitrogen in mepiquat chloride is a quaternary ammonium salt.
4.
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Amines and Heterocycles
ANS:
The nitrogen atom in fexofenadine is tertiary
1
Drawing Instructions: Draw structures corresponding to each of the given names.
5.
Draw: diisopropylamine
ANS:
6.
Draw: N,N-dimethylcyclopentanamine
ANS:
7.
Draw: 1,4-butanediamine
ANS:
H2NCH2CH2CH2CH2NH2
8.
Draw: p-methoxyaniline
ANS:
IUPAC Naming Instructions: Provide proper IUPAC names.
9.
2
Name:
Chapter 24
ANS:
N-isopropyll-N-methylcyclobutylamine
10.
Name:
ANS:
2,4-hexanediamine
11.
Name:
ANS:
methyl 2-aminobutanoate
12.
Name:
ANS:
N-ethylaniline
13.
Name:
ANS:
m-chloro-N,N-dimethylaniline
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Amines and Heterocycles
14.
Name:
ANS:
p-nitroaniline
Exhibit 24-2
Consider the reaction below to answer the following question(s).
Methamphetamine can be synthesized by reacting phenyl-2-propanone with methylamine in the
presence of H2/Ni.
15.
Refer to Exhibit 24-2. Identify the nucleophile in the initial reaction of phenyl-2-propanone
to yield intermediate A.
ANS:
The nucleophile is methylamine.
16.
a.
b.
c.
d.
Refer to Exhibit 24-2. Intermediate A is an example of:
an imine
an enamine
an iminium ion
an imide
ANS:
a
17.
Refer to Exhibit 24-2. Although the yield of methamphetamine is good, some unreacted
phenyl-2-propanone remains after the reaction is complete. Describe how methamphetamine
can be separated from phenyl-2-propanone.
ANS:
Dissolve the reaction mixture containing the ketone and amine in ether and extract with aqueous
HCl. The basic amine will dissolve in the aqueous layer as its hydrochloric salt. The neutral ketone
will remain in the ether layer. Separate the two layers and neutralize the aqueous layer with NaOH.
Extract the neutralized layer with ether. The purified amine will dissolve in the ether.
4
Chapter 24
Exhibit 24-3
Refer to the Table of pKas below to answer the following question(s):
pKas of Some Arylammonium Ions
Y
−H
−NH2
8.
pKa
4.63
1.74
6.15
Refer to Exhibit 24-3. Based on the pKas for their corresponding ammonium ions, which
arylamine above is the strongest base?
ANS:
p-aminoaniline
19.
Refer to Exhibit 24-3. Explain the difference in acidity between p-cyanoanilinium ion and
anilinium ion. Use both words and structures.
ANS:
p-Cyanoanilinium ion is a stronger acid (pKa = 1.74) than anilinium ion (pKa = 4.63). pCyanoanilinium ion gives up a proton on nitrogen more readily than anilinium ion because the
electron-withdrawing cyano group polarizes the benzene ring and thus decreases the stability of
the positively charged ion.
20.
Refer to Exhibit 24-3. Explain the difference in acidity between p-aminoanilinium ion and
anilinium ion. Use both words and structures.
ANS:
p-Aminoanilinium ion (pKa = 6.15) is less acidic than anilinium ion (pKa = 4.63) because paminoanilinium ion is stabilized by the electron-donating amino group. The p-amino group
donates electron density to the benzene ring, which helps stabilize the positive charge on nitrogen.
5
Amines and Heterocycles
21.
Rank the following compounds in order of increasing basicity. Label the least basic
compound "1" and the most basic compound "4". Place the number corresponding to the
compound's rank in the blank below the compound.
ANS:
22.
When a THF solution of phenyl-2-propanone and bromobutane is treated with 50% aqueous
NaOH, poor yields of 3-phenyl-2-heptanone result. However, when a small amount of
benzyltriethylammonium chloride is added to the reaction mixture, the yield of 3-phenyl-2heptanone increases to 90%. Explain these results.
ANS:
The reaction that is occurring is a carbonyl α-substitution reaction. Hydroxide ion abstracts a
proton from C-l on phenyl-2-propanone to generate an enolate ion, which then undergoes SN2
attack at the primary carbon of bromobutane. However, since the organic layer and water layer are
immiscible, the hydroxide is unable to come into contact with the ketone in the organic phase, so
there is little or no reaction.
When the quaternary ammonium salt is added, it dissolves in both the aqueous and organic layers.
When it moves into the organic layer, it takes hydroxide ion with it, to preserve the charge
neutrality. Once in the organic layer, hydroxide ion reacts with the ketone to generate the enolate,
which then undergoes SN2 displacement of bromide to give the carbonyl α-substitution product.
6
Chapter 24
Exhibit 24-4
Refer to the reaction below to answer the following question(s):
23.
Refer to Exhibit 24-4. Draw arrows on the structures provided below which show electron
flow in the complete stepwise mechanism for the reaction above.
7
Amines and Heterocycles
ANS:
24.
a.
b.
c.
d.
Refer to Exhibit 24-4. This reaction is an example of:
a Curtius rearrangement
a Hofmann elimination reaction
a Gabriel synthesis
a Hofmann rearrangement
ANS:
d
Exhibit 24-5
Give the major organic product(s) of each of the following reactions or sequences of reactions.
Show all relevant stereochemistry.
25.
8
Chapter 24
ANS:
26.
ANS:
27.
ANS:
28.
ANS:
9
Amines and Heterocycles
29.
ANS:
30.
ANS:
31.
ANS:
32.
ANS:
10
Chapter 24
33.
ANS:
34.
ANS:
35.
ANS:
36.
11
Amines and Heterocycles
ANS:
37.
ANS:
38.
ANS:
39.
12
Chapter 24
ANS:
40.
ANS:
41.
ANS:
42.
13
Amines and Heterocycles
ANS:
43.
ANS:
44.
ANS:
45.
ANS:
14
Chapter 24
Exhibit 24-6
Show how each of the following transformations might be best accomplished. More than one step
may be required. Show all reagents and all intermediate structures.
46.
ANS:
47.
15
Amines and Heterocycles
ANS:
48.
ANS:
49.
16
Chapter 24
ANS:
50.
ANS:
17
Amines and Heterocycles
Exhibit 24-7
Choose the best series of reactions for accomplishing each conversion below.
51.
a.
b.
c.
d.
ANS:
c
52.
a.
b.
c.
d.
ANS:
c
18
Chapter 24
53.
a.
b.
c.
d.
ANS:
a
54.
Mescaline is a hallucinogenic alkaloid isolated from peyote cactus. Synthesize mescaline
from 3,4,5-trimethoxytoluene. Show all reagents and all intermediate structures.
ANS:
19
Amines and Heterocycles
Exhibit 24-8
Refer to the data below to answer the following question(s):
Triclocarban is a disinfectant prepared from 3,4-dichloroaniline and 4-chlorophenylisocyanate.
55.
Refer to Exhibit 24-8. Prepare 4-chlorophenylisocyanate from toluene.
ANS:
56.
20
Refer to Exhibit 24-8. Prepare 3,4-dichloroaniline from benzene.
Chapter 24
ANS:
57.
Refer to Exhibit 24-8. Propose a mechanism for the reaction of 3,4-dichloroaniline and 4chlorophenylisocyanate to yield Triclocarban.
ANS:
58.
a.
b.
c.
From the list provided below, choose the best reagent(s) for each step in the following
synthesis. There is only one answer for each reaction.
NaBH4, ethanol
d. 1. HNO2, H2SO4
KCN, acetone
2. CuCN, KCN
1. LiAlH4, THF
e. 1. SnCl2, H3O+
2. H2O
2. NaOH, H2O
f. HNO3, H2SO4
21
Amines and Heterocycles
ANS:
step 1 = e; step 2 = d; step 3 = c
59.
22
Draw the structures for each of the intermediates in the boxes provided for the synthesis
below.
Chapter 24
ANS:
60.
Propose a structure that is consistent with the following spectral data:
MS:
IR:
1
H NMR:
M+ at 73
3350 cm 1 (weak, single band)
δ1.05 (br s, 1H), δ1.15 (t, 6H), δ2.65 (q, 4H)
−
ANS:
diethylamine, (CH3CH2)2NH
61.
Name the following substance. Atoms other than carbon and hydrogen are labeled.
ANS:
N,N-dimethylbutylamine
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Amines and Heterocycles
62.
Draw the product of the reaction of the following substance with 1.) LiAlH4 in ether, 2.)
H2O with the following substance. From what alkyl bromide could this substance be
produced when reacted with NaCN? Atoms other than carbon and hydrogen are labeled.
ANS:
63.
Write the equation for the reaction represented by the pKa of methyl amine.
ANS:
64.
Describe the importance of the formation of arenediazonium salts.
ANS:
Arenediazonium salts are stable and readily form from primary aryl amines upon treatment with
HNO2/H2SO4. These salts form an intermediate that readily undergo nucleophilic substitution
with a wide variety of nucleophiles. This allows for the preparation of a wide variety of
substituted aromatic compounds: nitriles, halides, carboxylic acids, phenols, etc.. Diazonium salts
also undergo coupling reactions to produce azo compounds.
24
Chapter 24
MULTIPLE CHOICE
1.
Classify the following amine. Atoms other than carbon and hydrogen are labeled.
a. primary
b. secondary
c. tertiary
d. quaternary
ANS: C
2.
Compared to pentylamine, pentane is
a. more soluble in water.
b. has a higher boiling point.
c. is less basic.
d. more offensive in terms of odor.
ANS: C
3.
The pKa of diethylammonium ion is 10.98. What is the pKb of diethylamine?
a. 3.02
c. 24.98
b. 14.00
d. 7.00
ANS: A
4.
a.
b.
c.
d.
e.
What is the percentage of neutral species in a 0.00500 M solution of pyridine at pH 9.50?
pKa of pyridine is 5.25.
25%
75%
50%
nearly 100%
close to 0%
ANS: D
5.
At which pH will a solution of a 0.00050 M solution of aniline (pKa = 4.63) contain the
greatest amount of the neutral species?
a. 2.74
c. 7.31
b. 4.63
d. 9.90
ANS: D
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Amines and Heterocycles
6.
Which of the following would best represent the form of ethylamine (pKa) at physiological
pH?
a. CH3CH2NH3+
c. CH3CH2NH–
b. CH3CH2NH2
d. a combination of a and b
ANS: A
7.
The amino acid phenylalanine has the structure below.
Which of the following is the best representation of this acid at pH 7.3?
a.
c.
b.
d.
ANS: C
8.
Which of the following methods of preparation of amines results in an amine with one less
carbon atom than the starting material?
a. reduction of a nitrile
c. reductive amination of a ketone
b. Gabriel synthesis from an alkyl halide
d. Hofman rearrangement of an amide
ANS: D
9.
Which of the following methods of preparation of amines can be used to prepare primary,
secondary, and tertiary amines?
a. reduction of a nitrile
b. Gabriel synthesis from an alkyl halide
c. reduction amination of a ketone
26
Chapter 24
d. Hofman rearrangement of an amide
e. None of these methods is applicable to all types of amines.
ANS: C
10.
a.
Which of the following is not classified as a heterocycle?
b.
c.
d.
e.
c and d
ANS: D
11.
An unknown substance produced the following spectrum.
This unknown is likely to be a:
a. primary amine
b. secondary amine
c. tertiary amine
d. amide
ANS: A
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Amines and Heterocycles
12.
Examine the following spectrum.
Which of the following would best describe this compound?
a. The compound may contain zero nitrogen atoms.
b. The compound may contain one nitrogen atoms.
c. The compound may contain two nitrogen atoms.
d. The compound may contain three nitrogen atoms.
e. a or c
f. b or d
g. The possible number of nitrogen atoms cannot be determined from the spectrum.
ANS: F
13.
a.
b.
c.
d.
e.
Which of the following is not a valid comparison of the spectral data for alkyl amines and
alkyl alcohols?
IR: strong absorptions > 3000 cm–1.
MS: peaks due α-cleavage
13
C NMR: adjacent carbon signal shifted downfield relative to an alkane
1
H NMR: proton bonded to the heteroatom appears over a wide range
All are valid comparisons between the spectral data of amines and alcohols.
ANS: E
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