994 Chapter 25 Amines

PROBLEMS
Nomenclature
25.41 Give a systematic or common name for each compound.

a. CH3NHCH2CH2CH2CH3 e. (CH3CH2CH2)3N i. CH2CH3

N
H

b. NH2 f. (C6H5)2NH j. CH3CH2CH2CH(NH2)CH(CH3)2

c. NH2 g. N C(CH3)3 k. NH2

CH2CH3

CH3
d. N h. O NH2 l. N(CH2CH3)2
CH2CH2CH3

25.42 Draw the structure that corresponds to each name.

a. cyclobutylamine f. N-methylcyclopentylamine
b. N-isobutylcyclopentylamine g. cis-2-aminocyclohexanol
c. tri-tert-butylamine h. 3-methyl-2-hexanamine
d. N,N-diisopropylaniline i. 2-sec-butylpiperidine
e. N-methylpyrrole j. (2S)-2-heptanamine
25.43 Draw all constitutional isomers of molecular formula C4H11N, and give an acceptable name for each amine.

Chiral Compounds
25.44 How many stereogenic centers are present in each compound? Draw all possible stereoisomers.
CH2CH3
CH3 +
a. N b. CH3CH2CHCH2CH2CH2 N CH2CH2CH2CH3
CH2CH3 CH3 CH3
CI–

Basicity
25.45 Which compound in each pair is the stronger base?

a. (CH3CH2)2NH or c. (CH3CH2)2NH or (ClCH2CH2)2NH

N

b. HCON(CH3)2 or (CH3)3N d. or
NH
N
H
25.46 Rank the compounds in each group in order of increasing basicity.
NH2 NH2 NH2
a. NH3 NH2 NH2 c.
O2N CH3 Cl

b. d. C6H5NH2 (C6H5)2NH NH2

N N N
H H

25.47 How does the pKa of the conjugate acid of benzylamine (C6H5CH2NH2) compare to the pKa’s of the conjugate acids of
cyclohexanamine (10.7) and aniline (4.6)? Explain your choice.
 Problems 995

25.48 Decide which N atom in each molecule is most basic and draw the product formed when each compound is treated with
CH3CO2H. Benazepril (trade name Lotensin) is a β blocker used to treat high blood pressure and congestive heart failure.
Varenicline (trade name Chantix) is used to help smokers quit their habit.
O
O
N
a. NH b. NH
N
N O varenicline
CH2CO2H
benazepril

25.49 Rank the nitrogen atoms in each compound in order of increasing basicity. Isoniazid is a drug used to treat tuberculosis,
whereas histamine (Section 25.6B) causes the runny nose and watery eyes associated with allergies.
O
N NH2
C
a. NHNH2 b.
N N
H
isoniazid histamine
25.50 Abilify is the trade name for aripiprazole, a drug used to treat depression, schizophrenia, and bipolar disorders. (a) Rank the N
atoms in aripiprazole in order of increasing basicity. (b) What product is formed when aripiprazole is treated with HCl?
O
Cl Cl

N N
NH

aripiprazole
O

25.51 Explain why m-nitroaniline is a stronger base than p-nitroaniline.

25.52 Explain the observed difference in the pKa values of the conjugate acids of amines A and B.

N
N
A B
pKa = 5.2 pKa = 7.29

25.53 Why is pyrrole more acidic than pyrrolidine?

NH NH

pyrrole pyrrolidine
pKa = 23 pKa = 44

Preparation of Amines
25.54 How would you prepare 3-phenyl-1-propanamine (C6H5CH2CH2CH2NH2) from each compound?
a. C6H5CH2CH2CH2Br c. C6H5CH2CH2CH2NO2 e. C6H5CH2CH2CHO
b. C6H5CH2CH2Br d. C6H5CH2CH2CONH2
25.55 What amide(s) can be used to prepare each amine by reduction?
H
N
a. (CH3CH2)2NH b. NH2 c. N(CH3)2 d.

25.56 What carbonyl and nitrogen compounds are needed to make each compound by reductive amination? When more than one set
of starting materials is possible, give all possible methods.
H
a. NH2 b. N c. (CH3CH2CH2)2N(CH2)2CH(CH3)2 d. N
C6H5 H

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 996 Chapter 25 Amines

25.57 Draw the product of each reductive amination reaction.

NH2 NH3
a. C6H5 c. C6H5 CHO
NaBH3CN NaBH3CN
O

NH2
(CH3)2NH
b. O d.
NaBH3CN NaBH3CN
O
25.58 How would you prepare benzylamine (C6H5CH2NH2) from each compound? In some cases, more than one step is required.
a. C6H5CH2Br c. C6H5CONH2 e. C6H5CH3 g. C6H5NH2
b. C6H5CN d. C6H5CHO f. C6H5COOH h. benzene

Extraction
25.59 How would you separate toluene (C6H5CH3), benzoic acid (C6H5COOH), and aniline (C6H5NH2) by an extraction procedure?

Reactions
25.60 What products are formed when N-ethylaniline (C6H5NHCH2CH3) is treated with each reagent?
a. HCl e. CH3I (excess) h. The product in (g), then HNO3, H2SO4
b. CH3COOH f. CH3I (excess), followed by Ag2O and ∆ i. The product in (g), then [1] LiAlH4; [2] H2O
c. (CH3)2C –
–O g. CH3CH2COCl j. The product in (h), then H2, Pd-C
d. CH2O, NaBH3CN
25.61 Draw the products formed when p-methylaniline (p-CH3C6H4NH2) is treated with each reagent.
a. HCl e. (CH3)2C –
–O h. NaNO2, HCl
b. CH3COCl f. CH3COCl, AlCl3 i. Step (b), then CH3COCl, AlCl3
c. (CH3CO)2O g. CH3COOH j. CH3CHO, NaBH3CN
d. excess CH3I
25.62 How would you convert CH3CH2CH2CH2NH2 into each compound?
a. CH3CH2CH2CH2NHCOC6H5 d. CH3CH2CH2CH2NHCH2C6H5
b. CH3CH2CH2CH2N – – C(CH2CH3)2 e. CH3CH2CH2CH2NHCH2CH3
c. CH3CH2CH –– CH2 f. [CH3CH2CH2CH2N(CH3)3]+ I –
25.63 Draw the products formed when each amine is treated with [1] CH3I (excess); [2] Ag2O; [3] ∆. Indicate the major product when a
mixture results.
CH3
a. CH3(CH2)6NH2 b. c. N d. e.
H NH2 N
NH2 H
CH3

25.64 What reagents are needed to convert acetophenone (C6H5COCH3) into each compound? In some cases, more than one step is
required.
N(CH3)2 NH2 OH
a. c. e. NHCH3
C6H5 C6H5 C6H5

O
b. d. C6H5 f. NHCH2CH2CH2CH3
C6H5 NCH2CH2CH3 C6H5

25.65 Answer the following questions about benzphetamine, a habit-forming diet pill sold under the trade name Didrex.
CH3 a. Label the stereogenic center(s).
b. What amide(s) can be reduced to form benzphetamine?
N
c. What carbonyl compound and amine can be used to make benzphetamine by reductive
amination? Draw all possible methods.
d. What products are formed by Hofmann elimination from benzphetamine? Label the major
benzphetamine product.

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 Problems 997

25.66 Draw the organic products formed in each reaction.

NH3
a. CH2CH2Cl excess f. C6H5CH2CH2NH2 + (C6H5CO)2O
(2 equiv)
O

[1] KOH NaNO2

b. NH g. NH
[2] (CH3)2CHCH2Cl HCI
[3] –OH, H2O
O

Sn NaBH3CN
c. Br NO2 h. NH + C6H5CHO
HCl

[1] LiAlH4
d. i. + O
[2] H2O
CN
N
H
[1] LiAlH4 [1] CH3I (excess)
e. CONHCH2CH3 j. CH3CH2CH2 N CH(CH3)2
[2] H2O [2] Ag2O
H [3] ∆

25.67 What is the major Hofmann elimination product formed from each amine?
CH3 NH2 C6H5
C6H5 NH2 H CH3 CH3 H
a. b. c.

H CH2CH3 C6H5 C(CH3)3 (CH3)3C NH2

C(CH3)3 CH2CH3 CH2CH3

25.68 Draw the product formed when A is treated with each reagent.
a. H2O e. CuCN h. C6H5NH2
N2+ Cl– b. H3PO2 f. HBF4 i. C6H5OH
c. CuCl g. NaI j. KI
CI A d. CuBr

25.69 Explain why so much meta product is formed when aniline is nitrated with HNO3 and H2SO4. For this reason, nitration of aniline
is not a useful reaction to prepare either o- or p-nitroaniline.
NH2 NH2 NH2 NH2
HNO3
+ +
H2SO4
O2N NO2
NO2
51% 47% 2%
para meta ortho

25.70 A chiral amine A having the R configuration undergoes Hofmann elimination to form an alkene B as the major product. B is
– O and CH3CH2CH2CHO. What are the structures of A
oxidatively cleaved with ozone, followed by CH3SCH3, to form CH2 –
and B?

Mechanism
25.71 Draw a stepwise mechanism for each reaction.

NaOH
a. Br + CH3CH2NH2 N + H2O + NaBr
Br
CH2CH3

H
O N
NaBH4
b. + H2O
CH3OH
NH2

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 998 Chapter 25 Amines

25.72 Draw a stepwise mechanism for the following reaction.

OH OH

HN H2C O N
mild acid
+ H2O

25.73 Propose a reason why aryl diazonium salts are more stable than alkyl diazonium salts.
25.74 Alkyl diazonium salts are unstable even at low temperature. They decompose to form carbocations, which go on to form
products of substitution, elimination, and (sometimes) rearrangement. Keeping this in mind, draw a stepwise mechanism that
forms all of the following products.

NaNO2 OH
+ +
HCl, H2O
NH2 OH

25.75 Tertiary (3°) aromatic amines react with NaNO2 and HCl to afford products of electrophilic aromatic substitution. Draw a
stepwise mechanism for this nitrosation reaction and explain why it occurs only on benzene rings with strong ortho, para
activating groups.

[1] NaNO2, HCl

N(CH3)2 ON N(CH3)2
[2] –OH

Synthesis
25.76 Devise a stepwise reaction sequence to convert 4-phenyl-2-butanone (PhCH2CH2COCH3) into each alkene:
(a) PhCH2CH2CH – – CH2; (b) PhCH2CH –
– CHCH3.
25.77 Devise a synthesis of each compound from benzene. You may use any other organic or inorganic reagents.
O
NH2 OH I
a. c. I CH3 e. g.
Br
NC Br
b. d. f. HO COOH h. N N OH
Br NHCOCH3

25.78 Devise a synthesis of each compound from aniline (C6H5NH2) as starting material.

CH3 COOCH2CH3 Br HO
CONHCH3
a. b. c. d. Br CH2OH e. N N
Br
Br CH3

25.79 Devise at least three different methods to prepare N-methylbenzylamine (PhCH2NHCH3) from benzene, any one-carbon organic
compounds, and any required reagents.
25.80 Safrole, which is isolated from sassafras (Problem 21.36), can be converted to the illegal stimulant MDMA
(3,4-methylenedioxymethamphetamine, “Ecstasy”) by a variety of methods. (a) Devise a synthesis that begins with safrole
and uses a nucleophilic substitution reaction to introduce the amine. (b) Devise a synthesis that begins with safrole and uses
reductive amination to introduce the amine.
O O

O NHCH3 O
MDMA safrole

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 Problems 999

25.81 Devise a synthesis of the hallucinogen mescaline (Section 25.6) from each starting material.
CH3O NH2
CH3O CH3O CH3O Br
Br
a. b. c.
CH3O
CH3O CH3O CH3O
CH3O
CH3O CH3O CH3O
mescaline

25.82 Synthesize each compound from benzene. Use a diazonium salt as one of the synthetic intermediates.
COOH

a. c. CH3 CH2NH2 e. HO CH3

Cl Br

OH Cl

b. d. CH3CH2 COOH f. N N NH2

Cl Cl
Cl
25.83 Devise a synthesis of each biologically active compound from benzene.
OH
H H
N NHCH3
N
a. b. c.
O O
Cl HO

Cl pseudoephedrine
propanil acetaminophen
(analgesic) (nasal decongestant)
(herbicide)
25.84 Devise a synthesis of each compound from benzene, any organic alcohols having three carbons or fewer, and any required
reagents.
Br
NH2 O
a. CH3O c. N CH CI e. F
HN
Br
O
C
O CH3 NH O
b. NH2 d. (CH3)2CHNH CO2CH3 f.

I
CN

Spectroscopy
25.85 Draw the structures of the eight isomeric amines that have a molecular ion in the mass spectrum at m/z = 87 and show two
peaks in their IR spectra at 3300–3500 cm–1.

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