20.2 Outline a procedure for separating a mixture

20.1 Outline a procedure for separating hexylamine from cyclohexane using dilute HCl, aqueous
NaOH, and diethyl ether.
Answer:
CH 3(CH 2) 5NH 2
dil HCl
ether
organic phase:
aqueous phase
dry distill
NaOH
ether
organic
phase
dry distill
CH 3(CH 2) 5NH 2
20.2 Outline a procedure for separating a mixture of benzoic acid, p-cresol, aniline and benzene
using acids, bases, and organic solvents.
Answer:
mixtures
organic phase
NH 2
NaOH,H2O ether COOH
aqueous phase
OH
dil HCl
ether
NaHCO 3
ether
organic phase:
NaOH
aqueous phase
ether
organic phase:
aqueous phase
dry distill
dry
HCl
organic
phase
distill
OH
recrystallization
dry distill
COOH
20.3 (a) Write resonance structure for the phthalimide anion that account for the acidity of
phthalimide. (b) Would you expect phthalimide to be more or less acidic than benzamide? Why?
(c) After step 2 of our reaction, several steps have been omitted. Propose reasonable mechanisms
for these steps.
Answer : (a)
O
N
O
O
N
(b) More acidic than benzamide . Because there are two C=O (carbonyl groups) attached to the N
which is a electric withdrawing group, so that the ccarbonyl group can stabilize the N anion. In
this case, phthalimide is much easier to release hydrogen, which means it is more acidic.
O
NH 2

(c)
O
O
N R H 2N NH 2
O
NH
NH
O HN R
O
O
H
N NH 2
N R
20.4 Outline a preparation of benzylamine using the Gabriel synthesis.
O
N
H
O
KOH X
O
O
OH
ethanol
N
H
H
N
NH2 several steps
O
K
N
H
H
O
O
N
N
O
O
H
H
NH
NH
O
O
+
N
+ H 2N
O
O
H 2N R
H 2N NH 2
20.5 Show how you might prepare each of the following amines through reductive amination:
a) CH3(CH2)3CH2NH2
H
NH3,H2,Ni O
b) C6H5CH2CH(NH2)CH3
O
c) CH3(CH2)4CH2NHC6H5
d) C6H5CH2N(CH3)2
O
H
NH 3,H 2,Ni
H 2,Ni
NH 2
NH 2
N
H
N
H
N
H
NH 2
NH 2
R

O
H
H
H 2,Ni
N
20.6 Reductive amination of a ketone is almost always a better method for the preparation of
amines of the type RCH(R’)NH2 than treatment of an alkyl halide with ammonia. Why would
this be true?
Answer:
I think the reasons are: 1) The multiple alkylations occurs when alkyl halide reacts with
ammonium, so the method is of very limited synthetic application. 2) I found that if it is treated by
ketone, the possible way is only one, so this reaction can be controlled well.
Above all, we can reach the conclusion easily that reductive amination of a ketone is almost
always a better method for the preparation of amines.
20.7 Show how you might utilize the reduction of an amide, oxime, or nitrile to carry out each of
the following transformations:
(a) Benzoic acid to benzylethylamine
(b) 1-Bromopentane to hexylamine
(c) Propanoic acid to tripropylamine
(d) Butanone to sec-butylamine
Answer:
(a)
(b)
(c) CH 3CH 2COOH
(d)
COOH COCl COHN
SOCl 2
NH 2C 2H 5
NaCN
CH2Br(CH2)3CH3 CH2CN(CH2)3CH3
SOCl 2
O
O
Cl
NH3
LiBH3CN NH(CH 2CH 2CH 3) 2
N
NH 2
O
(1) LiALH 4,Et 2O
(2) H 2O
(1) LiALH 4,Et 2O
(2) H 2O
N(CH 2CH 2CH 3) 2
(1) LiALH 4,Et 2O
(2) H 2O
H
N
NH 2(CH 2) 5CH 3
(CH 3CH 2CH 2) 3N

20.8 Using a different method for each part, but taking care in each case to select a good method,
show how each of the following transformations might be accomplished:
(a)
(b)
(c)
(d)
(e)
Answer:
(a)
H 3CO
H 3CO
H 3CO H 3CO CHNH 2CH 3
CH 3
NH 2
CH 2N(CH 3) 3Cl
O2N CH3 O2N NH2 HNO3 H3CO H3CO H2SO4 (b) H 3CO
(c) Cl 2/hv
(d)
O2N CH3
CH 3 CH 2CH 2NH 2
NO 2
(1) Fe,HCl
(2) OH
H 3CO NH 2
AlCl3 CH3COCl H3CO
O
CCH3
NH3 NaBH3CN H3CO CHNH2CH3 CH 2Cl
N(CH 3) 3
T.M
KMnO SOCl
4,H 2
O2N COOH O2N COCl
(1)NaN 3 O2N NH 2
(2)H2O

(e) CH 3
NBS/hv
CH 2Br NaCN
(i) LiAlH 4
CH 2CN (ii) H2O
20.9 Review the chemistry of amines given in earlier sections and provide a specific example for
each of the previously illustrated reactions.
Answer:
P963 The Hofmann Rearrangement
O
NH 2
P960 Reductive Amination
O
+ Br 2 + 4NaOH
+ NH 2
H 2O
H +
NH 2
CH 2CH 2NH 2
+ Na2CO3 + 2NaBr + 2H2O 20.10 Para-nitrosation of N,N-dimethylaniline (C-nitrosation) is believed to take place through an
electrophilic attack by NO + ions.
(a) Show how NO + ions might be formed in an aqueous solution of NaNO2 and HCl.
Answer:
O N O
H + H +
O N OH O N OH 2 O N
(b) Write a mechanism for p-nitrosation of N,N-demethylaniline.
Answer:
H2O N H
O N
N
(c) Tertiary aromatic amines and phenols undergo C-nitrosation reaction, whereas most other
benzene derivatives do not. How can you account for this difference?
Answer:
That is because nitrosonium cation is a kind of weak electrophile.
H
NO
N
N
H
NO

20.11 In the preceding examples of diazonium reactions, we have illustrated syntheses
beginning with the compounds (a)-(e) here. Show how you might prepare each
of the following compounds from benzene.
(a) m-Nitroaniline (c) m-Bromoaniline (e) p-Nitroaniline
(b) m-Chloroaniline (d) o-Nitroaniline
Solution:
(a)
(b)
(c)
(d)
(e)
HNO 3,H 2SO 4
HNO 3,H 2SO 4
HNO 3,H 2SO 4
HNO 3,H 2SO 4
NHCOCH3
SO3H
HNO 3,H 2SO 4
NO2
NO 2
NO2
NO2
HNO 3,H 2SO 4
NO2
HNO 3,H 2SO 4
Cl 2,Fe
Br 2,Fe
1) Fe,HCl
2) OH
1) Fe,HCl
2) OH
NO 2
NO 2
NO2
NH2
NHCOCH 3
SO 3H
NH2
Br
H2S NH3,C2H5OH NO 2
Cl
1) Fe,HCl
2) OH
1) Fe,HCl
2) OH
CH3COCl
NO2
1) dilute,H2SO4 NHCOCH3
NO2
2) OH -
CH 3COCl
1) dilute H 2SO 4
2) OH -
NH 2
NH 2
NH 2
NHCOCH 3
NH 2
NHCOCH 3
NH 2
NO 2
Br
Cl
NO 2
concd H 2SO 4
NO 2
HNO 3,H 2SO 4

20.12 Suggest how you might modify the preceding synthesis in order to prepare
3.5-dibromotolune.
Solution:
CH 3
NH 2
Br 2,Fe
Br
CH3
NH 2
H 2SO 4,HNO 2
Br
Br
CH 3
N 2
H 3PO 2,H 2O
20.13 (a) In Section 20.8D we showed a synthesis of m-fluorotoluene starting with m-toluidine.
How would you prepare m-toluidine from toluene? (b) How would you prepare m-chlorotoluene?
(c) m-Bromotoluene? (d) m-Iodotoluene? (e) m-Tolunitrile (m-CH3C6H4CN)? (f) m-Toluic acid?
Answer:
(a)
NHCOCH 3
NO 2
H 2SO 4
HNO 3
H 3O +
NO 2
Fe
HCl
NO 2
NH 2
Fe
HCl
NO 2
NaNO 2
HCl
(CH 3CO) 2O
Br
Br
NH 2 NHCOCH3
NH 2
N +
NCl -
NO 2
H3PO2 C2H5OH CH 3
H 2SO 4
HNO 3
Br

(b)
(c)
NHCOCH 3
NHCOCH 3
Cl
Br
H 2SO 4
HNO 3
H 3O +
Cl
H 2SO 4
HNO 3
H 3O +
Br
NO2
NO2
NH 2
NH 2
Fe
HCl
NaNO 2
HCl
Cl
Fe
HCl
NaNO 2
HCl
Br
(CH 3CO) 2O
NH2 NHCOCH 3
N +
NCl -
Cl
(CH 3CO) 2O
H3PO2 C2H5OH (1) Cl 2
NH 2 NHCOCH3
N +
NCl -
Br
(2) OH - , H 2O
heat
H3PO2 C2H5OH (1) Br 2
(2) OH - , H 2O
heat

(d)
(e)
NHCOCH 3
NHCOCH 3
NHCOCH 3
I
CN
NO2
H 2SO 4
HNO 3
I
H 3O +
H 2SO 4
HNO 3
Fe
HCl
H 2O
H +
NO2
NO 2
NH 2
Fe
HCl
I
Fe
HCl
NHCOCH3
(i) NaNO 2, HCl
(ii)
H3PO2 C2H5OH NaNO 2
HCl
NH 2
HNO 2
HCl
(CH 3CO) 2O
NH 2 NHCOCH3
N +
NCl -
CH3COCl
I
(1) I 2
H3PO2 C2H5OH NH 2 NHCOCH3
CN
NHCOCH 3
N 2 +
CuCN
(2) OH - , H 2O
heat
H 2SO 4
HNO 3

(f)
NHCOCH 3
NHCOCH 3
CN
NO2
H 2SO 4
HNO 3
Fe
HCl
H 2O
H +
NO 2
Fe
HCl
NHCOCH3
(i) NaNO 2, HCl
(ii) H3PO2 C2H5OH NH 2
HNO 2
HCl
CH3COCl
NH 2 NHCOCH3
CN
NHCOCH 3
H 3O +
N 2 +
CuCN
H 2SO 4
HNO 3
COOH
20.14 Starting with p-nitroaniline [Problem 20.11(e)] show how you might synthesize
1,2,3-tribromobenzene.
Answer:

Br
NH 2
NO2
CuBr
Br
N 2 +
(1) Br 2
Br
Br
Br
Br
NO 2
H3PO2 C2H5OH Br
NH 2
NO 2
Br
Fe
HCl
Br
Br
NaNO 2
HCl
Br
NH2
Br
Br
N 2 +
NO 2
NaNO 2
20.15 Outline a synthesis of orange Ⅱ from 2-naphthol and p-aminobenzenesulfonic acid.
OH
Answer:
N N
OrangeⅡ
SO 3 - Na +
Br
Br
HCl
Br

Step1
H SO HNO
2N 3H 2 +N2 SO3H Step2
OH
+
+N2 SO3H NaOH
H2O OH
N N
SO3 - Na +
20.16 Butter yellow is a dye once used to color margarine. It has since been shown to be
carcinogenic, and its use in food is no longer permitted. Outline a synthesis of butter yellow from
benzene and N, N-dimethylaniline.
N(CH3) 2
Answer:
N(CH 3) 2
CH 3COO - Na +
N N
Butter yellow
HNO3
H 2SO 4
NO 2
N N
Fe
H 3O +
N(CH3)2
NH2 HNO2
20.17 Azo compounds can be reduced to amines by a variety of reagents including stannous
chloride (SnCl2).
SnCl2 Ar N N Ar' ArNH2 + Ar'NH2 This reduction can be useful in synthesis as the following example shows:
4-Ethoxyaniline
SnCl 2
(1) HONO,H 3O +
(2)phenol,OH -
NN +
A(C 14H 14N 2O 2) NaOH,CH 3CH 2Br B(C16H 18N 2O 2)
two molar equivalents of C (C8H11NO) acetic anhydride phenacetin(C10H13NO2) Give a structure for phenacetin and for the intermediates A,B,C. (Phenacetin, formerly used as an

analgesic)
Answer: A:
H3CH2CO N N OH
B:
C:
H3CH2CO N N OCH2CH3
H 3CH 2CO NH 2
Phenacetin:
H 3CH 2CO NHCOCH 3
20.18 An amine A has the molecular formula C7H9N. Compound A reacts with benzene-sulfonyl
chloride in aqueous potassium hydroxide to give a clear solution; acidification of the soution gives
a precipitate. When A is treated with NaNO2 and HCl at 0-5℃, and then with 2-naphthol, an
intensely colored compound is formed. Compound A gives a single strong IR absorption peak a
815cm -1 . What is the structure of A?
Answer:
H3C NH2
20.19 Sulfonamides of primary amines are often used to synthesize pure secondary amines.
Suggest how this synthesis is carried out.
Answer:
O
O
R N S
H
O
R N R ,
H
Ar
O - H
R , Cl
O
+ - O S
O
R N
Ar
R ,
S
O
Ar
+ (1)H3 O,heat
(2)O-H

20.20 (a) Starting with aniline and assuming that you have 2-aminothiazole available, show how
you would synthesize sulfathiazole. (b) How would you convert sulfathiazole to
succinylsulfathiazole?
Answer:
(a)
(b)
H 2N
NH2
NH2
S
SO2NH
N
(CH 3CO) 2O
S
N
H 2N
O
NHCCH 3
SO 2NH
S
N
2-Aminothiazole
O
O
O
-HCl
O
NHCCH 3
S
N
HOSO2Cl 80℃
(1)dilute HCl,heat
(2)HCO 3 -
O
O
NHCCH 3
SO 2Cl
NH2
SO2NH
S
Sulfathiazole
NHCCH2COOH
SO2NH
S
N
Succinylsulfathiazole
N

20.21 Write structural formulas of the following compounds:
(a) Benzylmethylamine
NH
N
N
(b) Triisopropylamine
(c) N-Ethyl-N-methylaniline
N
(d) m-Toluidine
(e) 2-Methylpyrrole
(f) N-Ethylpiperidine
(g) N-Ethylpyridinium
N
H
NH2

HO
O
O
N +
(i) Indole
(h) 3-Pyridine carboxylic acid
N
(j) Acetanilide
N
H
(k) Dimethylaminium chloride
(l) 2-Mehtylimidazole
(m) 3-Amino-1-propanol
HO NH2 (n) Tetrapropylammonium chloride
N
H
NH 2 + Cl -
N
N
H

O
HO
N
O
Cl -
N +
(o) Pyrrolidine
(p) N,N-Dimethyl-p-toluidine
(q) 4-Methoxyaniline
NH2
(r) Tetramethylammonium hydroxide
(s) p-Aminobenzoic acid
(t) N-Methylaniline
NH2
NH
OH -
20.22 Give common or systematic names for each of the following compounds:
HN
N +

(g)
(a) CH3CH2CH2NH2 Propylamine
(b) C6H5NHCH3 Methylphenylamine
(c) (CH 3) 2CHN(CH 3) 3I - Isopropyl trimethyl ammonium iodide
(d) o-CH3C6H4NH2 o-toluidine
(e) o-CH3OC6H4NH2 o-methoxy aniline
(f)
N
H
N
N NH 2
N
1H-Pyrazole
2-amino pyrimidine
(h) C 6H 5CH 2NH 3 + Cl - Benzyl-ammonium chloride
(i) C6H5N(CH2CH2CH3) 2 N,N-dimethylaniline
(j) C6H5SO2NH2 Benzenesulfonamide
(k) CH 3NH 3 + CH3CO 2 - Methyl ammonium acetate
(l) HOCH 2CH 2CH 2NH 2 3-Amino-1-propanol
(m)
(n)
N
N
N
H N Purine
N
CH 3 1-Methyl pyrrole
20.23 Show how you might prepare benzylamine from each of the following compounds:
(a) Benzonitrile
(b) Benzamide
(c) Benzyl bromide
(d) Benzyl tosylate
(e) Benzaldehyde
(f) Phenylnitromethane

(g) Phenlacetamide
(a)
(b)
(c)
(d)
(e)
(f)
(g)
O
O
C
N
NH 2
H 2
C Br
O
O S
NH 3
O
NaBH 3CN
N +
O
O -
O
LiAlH 4 Et 2O
H 2O
NH 3
LiAlH 4 Et 2O
H 2O
Fe HCl
NH 2
+ Br 2 + NaOH
NH 3
H2
C NH 2
H 2
C NH 2
NH 2
NH 2
NH 2
H 2
C NH 2
NH2
+ CO 3 2-
20.24 Show how you might prepare aniline from each of the following compounds:
(a) Benzene
(b) Bromobenzene
(c) Benzamide
Answer:

(a)
(b)
(c)
O
HNO 3
Br NaNH2
C NH 2
NH 3
+ Br 2 + NaOH
NO 2
NH 2
Fe HCl
NH2
NH 2
+ CO 3 2-
20.25 Show how you might synthesize each of the following compounds from butyl alcohol:
(a) Butylamine (free of 2 。 and 3 。
(b) Pentylamine
(c) Propylamine
OH
OH
HBr
amines)
HBr
OH Br
K 2Cr 2O 7
(d) Butylmethylamine
NH2
CH 3I
O
OH
NH 3
Br
1.
O
O
NK
2. NH 2NH 2
1. NaCN
2. LiAlH 4
O
NH 2
Br 2 / OH -
20.26 Show how you might convert aniline into each of the following compounds. (You need not
repeat steps carried out in earlier parts of this problem.)
(a) Acetanilide
NH 2 NH C
(CH 3CO) 2O
(b) N-Phenylphthalimide
O
NH
NH 2
NH2
NH 2

O
O
O
(c) P-Nitroaniline
NH C
O
(d) Sulfanilamide
O
HN
C
NH C
C 6H 5NH 2
(e) N, N-Dimethylaniline
NH 2
(f) Fluorobenzene
HO
NH2 (g) Chlorobenzene
HO
NH2 (h) Bromobenzene
HO
NH2 (i) Iodobenzene
HO
NH2 (j) Benzonitrile
H 2SO 4/HNO 3
O
O
S
O
NH 2
2 CH 3I N
N O
0 - 5℃
N O
0 - 5℃
N O
0 - 5℃
N O
0 - 5℃
- O
O
N +
conc H 2SO 4
HO 3S
dilute HCl
N 2
N 2
N 2
N 2
N
O
O
H 2N
NH
HBF 4
heat
CuCl
CuBr
CuI
C
O
NH C
O
NH 3
H 2O
O
S
O
Cl
Br
I
- O
O
NH 2
F
N +
NH 2

HO
NH2 (k) Benzoic acid
(l) Phenol
(m) Benzene
CN
HO
NH2 HO
NH2 N O
0 - 5℃
H 2O
N O
0 - 5℃
N O
0 - 5℃
(n) P- (Phenylazo) phenol
NH 2 NaNO 2
HCl
HO
(o) N, N-Dimethyl-p-(phenylazo)aniline
NH 2 NaNO 2
HCl
O
N 2
CuCN
N 2Cu2O, Cu 2+ ,H 2O
N 2
N N
N N
H 3PO 2, H 2O
OH
N(CH 3) 2
CN
OH
N
N
N
N
OH
N(CH 3) 2
20.27 What products would you expect to be formed when each of the following amines reacts
with aqueous sodium nitrite and hydrochloric acid?
(a) Propylamine (c)N-Propylaniline (e)p-Propylaniline
(b)Dipropylamine (d)N,N-Dipropylaniline
Answer:
(a)

CH 3CH 2CH 2 NH 2
CH 3CH 2CH 2OH
(b)
NaNO 2
HCl
CH 3CH 2CH 2
CH 3CH 2CH 2 N N
CH3CH=CH2 CH3CH2CH2Cl CH 3CH 2CH 2 NH NaNO 2
HCl
H3CH2CH2C H3CH2CH2C
(c)
(d)
HN
H 3CH 2CH 2C
(e)
NH 2
CH 2CH 2CH 3
N
CH2CH2CH3
NaNO2
HCl
CH 2CH 2CH 3
NaNO2
HCl
O
NaNO2
HCl
N
CH 3CH 2CH 2
N
H3CH2CH2C
N
N
CH 3CHCH 3
CH 3CHClCH 3
CH 2CH 2CH 3
N
N O
CH 2CH 2CH 3
N N
CH2CH2CH3
CH 3CH 2OHCH 3
20.28 (a) What products would you expect to be formed when each of the following
O

Answer:
NH2
amines in the preceding problem reacts with benzenesulfonyl chloride and excess
aqueous potassium hydroxide? (b) What would you observe in each reaction? (c)
What would you observe when the resulting solution or mixture is acidified?
CH2CH2CH3
H3CH2CH2C
HN
N
TsCl
KOH
CH 2CH 2CH 3
CH2CH2CH3
TsCl
KOH
Ts
TsCl
KOH
N
CH 2CH 2CH 3
CH3CH2CH2 NH
KOH
H3CH2CH2C H3CH2CH2C
CH 3CH 2CH 2 NH 2
TsCl
KOH
TsCl
Ts
N
HA
No reaction
CH 2CH 2CH 3
CH 3CH 2CH 2
CH 3CH 2CH 2 N
Ts
N
HA
Ts
Ts
NH
CH 2CH 2CH 3
CH 3CH 2CH 2 NH
20.29 (a) What product would you expect to obtain from the reaction of piperidine with aqueous
sodium nitrite and hydrochloric acid? (b) From the reaction of piperidine and benzenesulfonyl
chloride in excess aqueous potassium hydroxide?
Answer:
Ts

(a)
N
N
O (b)
20.30 Give structure for the products of each of the following reactions:
(a) Ethylamine + benzoyl chloride O
(b) Methylamine + acetic anhydride
(c) Methylamine + succinic anhydride O
(d) Product of (c)
O
(e) Pyrrolidine + phthalic anhydride O O
(f) Pyrrole +acetic anhydride
N
O
S
O
HN
N
N
H
O
N
O
N
O
O
HN
OH
OH

(g) Aniline + propanoyl chloride
(h) Tetraethylammonium hydroxide
(i)
m-Dinitrobenzene + H 2S
p-Toluidine + Br 2(excess) H2O
NH 3
C 2H 5OH
(j)
Br
20.31 Starting with benzene or toulene, outline a synthesis of each of the following compounds
using diazonium salts as intermediates. (You need not repeat syntheses carried out in earlier of this
proplem.)
(a) p-Fluorotoluene
(b) o-Iodotoluene
(c) p-Cresol
(d) m-Diachlorobenzene
(e) m-(C6H4(CN)2
(f) m-Iodophenol
(g) m-Bromobenzenontrile
(h) 1,3-Dibromo-5-nitrobenzene
(i) 3,5-Dibromoaniline
(j) 3,4,5-TriBromophenol
(k) 3,4,5-Tribromobenzonitrile
(l) 2,6-Dibromobenzoic acid
(m) 1,3-Dibromo-2-iodobenzene
(n) 4-Bromo-2-nitrotoluene
(o) 4-Methyl-3-nitrophenol
O
O
N
Br
O
HN
N
NH 2
NH 2

H 3C
(q)
H3C
(r)
H3C
NC
Answer:
(a)
(b)
(c)
H 2N
(d)
CH3
heat
HNO 3
H 2SO 4/warm
F
HNO
CH3
3
H2SO4/warm CH 3
Br
N N
N N
O 2N
NO 2
CH 3
CH 3
HONO/H 2SO 4
OH
CH 3
CH 3
Fe/HCl
OH
H 2N
Fe/HCl
CH3
NH2 HONO
HCl
O 4SHN 2
CH 3
CH 3
Cu,Cu 2O,H 2O
(1)HONO,H
(2)HBF4 HO
N2Cl
CH 3
F 4BN 2
CH 3
KI CH 3
CH 3
I

(e)
(f)
O2N
(g)
O 2N
(h)
O 2N
(i)
Br
O 2N
(j)
(k)
HNO 3
H 2SO 4
HONO,HCl
HNO3 NO2 NO2
H2SO4 NH 2
NH 2
NH 2
H3O heat
NO 2
Br
O 2N
HONO/HI
O2N
NO 2
Cl
Cl 2/FeCl 3
Fe/HCl
N 2I
KI
H 2N
O2N
Cl
N 2Cl
NH 2
CuCl
I
NO 2
Cl
HCl,HONO 2
ClN 2
Fe/HCl
Cl
Cl
N 2Cl
CuCN
NH 2
NC
Fe/HCl (1)HCl,HONO2 I
(2)Cu,Cu2O,H2O HONO/HBr CuBr
Zn/HCl (1)HCl,HONO2 N2Br Br
Br
(2)CuCN
Br 2/FeBr 3
CH 3COCl
O 2N
Fe/HCl
Br
O 2N
Br
Br
NH 2
O 2N
H2S,NH3,C2H5OH NO2
Br
O2N NH2 (1)HBr,HONO
(2)CuBr
Br
Br
O 2N
H 2N
H 2N
O
HNO3 NHCCH3 H2SO4/warm O2N
O
NHCCH3
NH2
(1)HBr,HONO
(2)CuBr
Br
O 2N
HO
NC
CN
I
Br
Br
Br 2/FeBr 3 O2N NHCCH 3
Br
Br
(1)Zn/HCl
(2)HI,HONO
O2N Br
HO Br
(3) Cu2O, Cu2+, H2O Br
Br
Br
Br
O

Br
O 2N Br
(l)
(m)
Br
(1)Zn/HCl
(2)HCl,HONO
(3)CuCN
Br
NC Br
HNO3 Br2/FeBr3 CH3 O2N CH3 O2N
CH3 H2SO4/warm (1)HCl,HONO
(2)H3PO2/heat O 2N NH 2
(n)
Br
Br
(1)HCl,HONO
(2)H3PO2,H2O H 2N
(o)
O2N
(p)
Br
(q)
CH 3
Br
Br
(1)HI,HONO
(2)KBr
Br
Br
I
CH 3
(1)HBr,HONO
(2)CuBr
KMnO 4
Br
Br
Br
Br
O 2N I
NO 2 NO 2
HNO3/H2SO4 CH3
O2N NO2
CH3
NO 2
CH 3
Br
H 2S, NH 3
H2N
Br
Br
Br
COOH
Zn/HCl
NO 2
CH 3
Zn/HCl
H2N
Br
Br
Br
CH 3
H 2N I
(1)HCl,HONO
CH3
HO
(2)Cu,Cu2O,H2O Zn/HCl (1)HCl,HONO
Br
CH3 Br
(2)CuCN
NH 2
Br
CN
NO2
CH3
CH 3

(r)
(1)H2SO4/HONO NH2
(2)Cu,CU2O,H2O OH
ClN 2
ClN2 CH3 + H3C
OH
20.32 Write equations for simple chemical tests that would distinguish between
(a) Benzylamine and benzamide
(b) Allyamine and popylamine
(c) P-Toluidine and N-methylaniline
(d) Cyclohexylamine and piperidine
(e) Pyridine and benzene
(f) Cyclohexylamine and aniline
(g) Triethylamine and diethylamine
(h) Tripropylammonium chloride and tetrapropylammonium chloride
(i) Tetrapropylammonium chloride and tetrapropylammonium hydroxide
Answer:
(a)
(b)
NH 2
CONH 2
Br 2
Br 2
Br
NH 2
Br
no reaction
Br
CH 3
H3C
H 3C
N N
N N
OH
CH 3
OH

(c)
(d)
(e)
(f)
NH 2
CH 3
NHCH 3
NH2
H
N
N
NH 2
NH 2
PhSO 2Cl
PhSO 2Cl
HCl/H 2O
Br 2
Br 2
Br
NHSO 2Ph
CH 3
H 3CN SO 2Ph
NHSO 2Ph
SO 2Ph
N
N
H
Br
no reaction
Cl
no reaction
NaOH
NaOH
NH 2
NSO2Ph
CH3
no reaction
NSO 2Ph
no reaction

(g)
(h)
NH2
NH 2
N
NH
Br 2
NHCl
NCl
PhSO 2Cl
no reaction
NH 2
Br Br
NaOH
Br
no reaction
NSO 2Ph
no reaction
(i)
Tetrapropylammonium chloride dissolves in water to give a neutral solution, however,
tetrapropylammonium hydroxide gives a strong basic solution.
20.33 Describe with equations how you might separate a mixture of aniline, p-cresol, benzoic acid,
and toluene using ordinary laboratory reagents.
Solution:
N

mixture H+
separation
NH3
OH -
mixture OH- separation
NH2
H +
CH 3
NaHCO 3
separation
OH
CH 3
COONa
20.34 Show how you might synthesize β-aminopropionic acid (H 3NCH 2CH 2CO 2 - ) from
succinic anhydride. (β-Aminopropionic acid is used in the synthesis of pantothenic acid; see
Problem 18.34.)
Solution:
O
O
O
O
+ NH 3
H 2C
C
H 2C C
O
NH 2 Br/OH -
OH
H 2C NH 2
H 2C
C
O
O
H +
H +
COOH
H 3NCH 2CH 2CO 2
20.35 Show how you might synthesize each of the following form the compounds indicated and
any other needed reagents.
(a) (CH3)3 + N(CH2)10 + N(CH3)32Br - from 1,10-decanediol
(b) Succinylcholine bromide (see the chapter opening vignette) from succinic acid,
2-bromoethanol, and trimethylamine
Answers:
(a)
(b)
HO(CH 2) 10OH 2HBr Br(CH 2) 10Br 2N(CH 3) 3 H3C N
HOOC
2N(CH 3) 3
COOH
2BrCH 2CH 2OH
O O
CH 3
CH 3
(CH3) 3N(CH2) 2OC(CH2) 2CO(CH2) 2N(CH3) 3 2Br
(CH 2) 10N
CH 3
CH 3
O O
2Br
CH 3
Br(CH 2) 2OC(CH 2) 2CO(CH 2) 2Br

20.36 A commercial synthesis of folic acid consists of heating the following three compounds with
aqueous sodium bicarbonate. Propose reasonable mechanisms for the reactions that lead to folic
acid.
Answers:
H 2N
H 2N
N
N
N
OH
H2N
N
OH
N
NH 2
NH 2
N
N
+
N
OH
Br
O
NH2
NH2
Br
Br
+
O
CHBr 2CCH 2Br
H 2N
COOH
+ H 2N CONHCHCH 2CH 2COOH
HCO 3,H 2O
Folic acid (~10%)
N
N
OH
NH 2
H
N CONHCHCH 2CH 2COOH
COOH
20.37 When compound W(C15H17N) is treated with benzenesulfonyl chloride and aqueous
potassium hydroxide, no apparent change occurs. Acidification of this mixture gives a clear
solution. The 1 H NMR spectrum of W is shown in Fig.20.7. Propose a structure for W.
Answer:
N
N-benzyl-N-ethylaniline
20.38 Propose structures for compounds X, Y, and Z.
X(C 7H 7Br) NaCN
Y(C 8H 7N) LiAlH 4
Z(C 8H 11N)
The 1 H NMR spectrum of X gives two signals, a multiplet at δ7.3(5H) and a singlet at δ
4.25(2H); the 680-840-cm -1 region of the IR spectrum of Y is similar to that of X: multiplet at δ
7.3(5H), singlet at δ3.7(2H). The 1 H NMR spectrum of Z is shown in Fig.20.8.
Answer:
X
Br
; Y
CN
; Z
N
Br
Br
Br
NH 2
H 2N
.
H 2N
N
N
N
OH
N
OH
H
N
N
N
N
HCO 3 -
Br
Br
Br

20.39 Using reactions that we have studied in this chapter, propose a mechanism that accounts for
the following reaction:
O
Answer:
O
CH2CH2CN
CH2CH2CN
H 2,Pd
H 2,Pd
20.40 Give structures for compounds R-W:
O
H
N
-H 2 O
N - Methylpiperidine + CH 3I R(C 7H 16NI) Ag 2O
H 2O
T(C 7H 15N)
Answer:
R:
U:
N I
N I
CH 3I
U(C 8H 19NO)
S:
V:
H
Ag 2O
H 2O
N OH
N OH
V(C 8H 19NO)
T:
N
H
N
H 2,Pd
S(C 7H 17NO)
heat W(C 5H 8+H 2O+(CH 3) 3N)
20.41 Compound A (C10H15N) is soluble in dilute HCl. The IR absorption spectrum shows two
bands in the 3300-3500cm -1 region. The broadband proton-decoupled 13 C spectrum of A is given
in Fig. 20.9. Propose a structure for A.
Answer:
W:
N
H
N

H 3CH 2C
NH 2
CH 2CH 3
20.42 Compound B, an isomer of (Problem 20.41), is also soluble in dilute HCl. The IR
spectrum of B shows no bands in the 3300-3500 cm -1 region. The broadband proton-decoupled
13
C spectrum of B is given in Fig. 20.9. Propose a structure for B.
Answer:
H 3CH 2C
N
CH 2CH 3
20.43 Compound C (C9H11NO) gives a positive Tollens’ test and is soluble in dilute HCl. The IR
spectrum of C shows a strong band near 1695 cm -1 but shows no bands in the 3300-3500 cm -1
region. The broadband proton-decoupled 13 C NMR spectrum of C is shown in Fig. 20.9. Propose a
structure for C.
Answer:
CHO
N
H3C CH3 20.44 Outline a synthesis of acetylcholine iodide using as organic starting materials:
dimethylamine, oxirane, and acetyl chloride.

H 3C N
Answer:
H 3C
H
N
CH3
CH3
H 2
C
I
H 2
C O
Acetylcholine iodide
CH 3
H 2C
O
O
C
CH2 H 3C N
CH 3I
CH3
CH3
H 3C N
CH3
CH3
CH3COCl CH2CH2OH H3C N
CH2CH2O
I
O
C
CH3
CH3
CH2CH2O
20.45 Ethanolamine, HOCH2CH2NH2, and diethanolamine, (OHCH2CH2)2NH, are used
commercially to form emulsifying agents and to absorb acidic gases. Propose syntheses of these
two compounds.
Answer:
O
+ NH HOCH 3 2CH2NH2 O
+ HOCH2CH2NH2 (HOCH2CH2) 2NH
20.46 Diethylpropion (see the following structure) is a compound used in the treatment of
anorexia. Propose a synthesis of diethylpropion starting with benzene and using any other needed
reagents.
Answer:
O
C
CH3

NH(C 2H 5) 2
CH 3CH 2COCl
AlCl 3
O
O
N(C2H5)2
CH 2CH 3
Br 2
O
CHCH 3
20.47 Suggest an experiment to test the proposition that the Hofmann reaction is an intramolecular
rearrangenment, i.e.,one in which the migrating R group never fully separates from the amide
molecule.
A:
C 6H 5H 2C
O
CNH2
Br 2, NaOH, H 2O
C6H5H2C
H3C H
H3C
H
From the example above, the R group migrates to nitrogen with its electrons, but without
inversion.
20.48 Using as starting materials propanoic acid, aniline, and 2-naphthol, propose a synthesis of
naproanilide, a herbicide used in rice paddies in the Orient.
OH
O
OH
Cl 2
P
Cl
Cl
O
O
Cl
NH 2
20.49 When phenyl is isothiocyanate, C6H5N=C=S, is reduced with lithium aluminum hydride,
the product formed has these spectral data:
MS (m/z): 107, 106
IR (cm -1 ): 3330(sharp), 3050, 2815, 760, 700
1
H NMR (δ ): 2.7(s), 3.5(board), 6.6(m), 7.2(t)
13
C NMR (δ ): 30(CH2), 112(CH), 117(CH), 129(CH2), 150(C)
(a) What is the structure of the product?
(b) What is the structure that account for the 106m/z peak and how is it formed? (It is an iminium
O
O
Cl
N
H
H
N
NH 2
Br

ion.)
Answer:
(a)
(b)
H
N
H
N
CH 3
CH 3
-e -
H
Ph N CH2
H
m / z 107
- H 2O
Ph N CH2
H
m / z 106
*20.50 When N,N’-diphenylurea (A) is reacted with tosyl chloride in pyridine, it yields product B.
H
N
O
A
H
N
The spectral data for B include:
MS (m/z): 194 (M + )
IR (cm -1 ): 3060, 2130, 1590, 1490, 760, 700
1
H NMR (δ): only 6.9-7.4 (m)
13
C NMR (δ): 122 (CH), 127 (CH), 130 (CH), 149 (C), and 163 (C)
(a) What is the structure of B?
(b) Write a mechanism for formation of B.
Answer:
N C N

H
N
O
A
H
N
H
N N
OH
N C N
20.51 Propose a mechanism that can explain occurrence of this reaction:
N
O
Answer:
N
O
COOH
COOH
N
O
+
H
O O O
N
O
COOH
O
O
N
O
O
H
C
COOH O O O
O
O
+
CH3
N
O
O
C
O
N
O
O O
O
O
H
TsCl
N
O
O
O
CH 3
H
N N
N
OTs
C
COOH
O
O O
20.52 When acetone is treated with anhydrous ammonia in the presence of anhydrous calcium
chloride (a common drying agent), crystalline product C is obtained on concentration of the
organic liquid phase of the reaction mixture.
These are spectral data for product C:
MS (m/z): 155 (M + ·), 140
IR (cm -1 ): 3350 (sharp), 2850-2960, 1705
1
H NMR (δ): 2.3 (s, 4H), 1.7 (1H; disappears in D2O), and 1.2 (s, 12H)
(a) What is the structure of C?
N
O
O
C
O
H
N
O
H
O

(b) Propose a mechanism for formation of C.
Answer:
HN O
OH
NH
O
NH2
O
CH3
N
CH 3
O
N
CH 2
OH
HN O