CHAPTER 21
Preparation of Nitriles
Reactions of Nitriles
O
R
Br
R
C
R C N
N
OH
R
O
R
R C N
NH2
O
R C N
R
R
H H
R C N
R
Solutions
21.1.
a) IUPAC name = pentanedioic acid
Common name = glutaric acid
b) IUPAC name = butanoic acid
Common name = butyric acid
c) IUPAC name = benzene carboxylic acid
Common name = benzoic acid
d) IUPAC name = butanedioic acid
Common name = succinic acid
e) IUPAC name = ethanoic acid
Common name = acetic acid
f) IUPAC name = methanoic acid
Common name = formic acid
21.2.
O
Cl
OH
a)
b)
O
Cl O
OH
c) HO
O
OH
NH2
517
518
CHAPTER 21
21.3.
a) 3,3,4,4-tetramethylhexanoic acid
b) 2-propylpentanoic acid
c) (S)-2-amino-3-phenylpropanoic acid
21.4. The compound below is more acidic because its conjugate base is resonance
stabilized. The conjugate base of the other compound is not resonance stabilized.
O
OH
H3C
21.5.
The conjugate base is resonance stabilized, with the negative charge spread over two
oxygen atoms, just like with carboxylic acids:
O
O
O
O
21.6. meta-Hydroxyacetophenone should be less acidic than para-hydroxyacetophenone,
because in the conjugate base of the former, the negative charge is spread over only one
oxygen atoms (and three carbon atoms). In contrast, the conjugate base of parahydroxyacetophenone has the negative charge spread over two oxygen atoms (more
stable).
21.7.
O
H
O
O
H
+
K
OH
H
formic acid
O
H2O
+
K
potassium formate
21.8. The conjugate base predominates under these conditions:
[conjugate base]
[acid]
= 10
(pH - pKa)
= 10
(5.76 - 4.76)
1
= 10 = 10
21.9.
a) 2,3-dichlorobutyric acid is the most acidic and 3,4-dimethylbutyric acid is the least
acidic.
b) 2,2-dibromopropionic acid is the most acidic and 3-bromopropionic acid is the least
acidic.
CHAPTER 21
21.10.
a) Na2Cr2O7, H2SO4, H2O
b) Na2Cr2O7, H2SO4, H2O
c) CH3Cl, AlCl3 followed by Na2Cr2O7, H2SO4, H2O
d) NaCN, followed by H3O+, heat
or Mg, followed by CO2, followed by H3O+
e) Na2Cr2O7, H2SO4, H2O
f) Mg, followed by CO2, followed by H3O+
21.11.
1) Mg
2) CO2
Br
OH
3) H3O+
4) LAH
5) H2O
a)
1) Na2Cr2O7, H2SO4, H2O
2) LAH
3) H2O
OH
1) NBS, heat
2) NaOH
b)
21.12.
a) propionic anhydride
b) N,N-diphenyl-propionamide
c) dimethylsuccinate
d) N-ethyl-N-methylcyclobutanecarboxamide
e) butyronitrile
f) propyl butyrate
g) succinic anhydride
h) methyl benzoate
i) phenyl acetate
21.13.
O
O
O
a)
O
O
O
O
O
b)
c)
N
H
d)
Cl
519
520
CHAPTER 21
21.14.
a)
H N
O
O
N
Cl H
Cl
- Cl
N H
O
O
N
N
H
b)
O
O
H O Me
Cl
O
H
O
Cl Me
H
O
Me
- Cl
H O Me
O
OMe
c)
O
O
O
O
O
O
- Cl
O
O
Cl
Cl
d)
O
NH3
O
H
- Cl
O
Cl
H
N
N H
Cl
O
H
H
H
NH3
O
NH2
521
CHAPTER 21
e)
H
H O
O
O
H
NH2
H
OH
H O H
NH2
H N
H
H
OH
H O H
O
H
OH
H N
H
H
O
NH4
+
O
NH3
OH
H
O
H
OH
H
- NH3
OH
NH3
OH
f)
O
O
O
OH
O
OH
OMe
OMe
H
+ MeO
O
+
O
MeOH
g)
H
H O
Me
O
O
OH
H
OH
Me O H
OH
OH
Me
O
H
OH
Me O H
OH
Me
O
H
O
Me O H
OMe
H
OH
O
OMe
Me
H
O
H
O
O H
Me
522
CHAPTER 21
21.15.
O
O
Cl
OH
O
Cl
-
O
H
Cl
O
H
OH
O
O
21.16.
H
H O
O
O
H
OH
HO
HO
H
OH
OH
HO
O
H
H
O
H
O
O
H
H O OH
O
H
- H2O
O
H
O
O
H
O H
H
HO
H
OH
O
21.17.
O
H
N
H
H O
Me
H
O
Me
H
N
H O Me
O
HO
H
H
N
H O Me
HO
OMe H
N
H
O
H
O
H2N
H
H O Me
OMe
H2N
MeO
O
OMe
HO
H
N
H
Me
CHAPTER 21
21.18.
O
1) xs LAH
Cl
a)
O
OH
2) H2O
OH
1) xs PhMgBr
Cl
b)
Ph
Ph
2) H2O
1) LiAl(OR)3H
O
OH
2) H2O
Cl
3) EtMgBr
4) H2O
c)
OH
O
1) Et2CuLi
Cl
d)
2) LAH
3) H2O
O
O
OH
Cl
O
e)
O
O
N H
Cl
N
f)
21.19.
OH
O
1) Na2Cr2O7, H2SO4, H2O
2) SOCl2
Cl
523
524
CHAPTER 21
21.20.
O
H H
C C H
H H
Cl
Cl
O
O
H H
H C C
H H
H
O
H
O H
H
H
H
O H
H
OH
O
H
H
O
H
21.21.
O
O
O
O
OH
O
O
HO
+
a)
O
O
H
N
O
O
N
HO
O
+
b)
O
OH
O
O
O
O
c)
H
N
O
O
O
O
N
O
+
d)
O
+
OH
OH
525
CHAPTER 21
21.22.
1) NaOH
2) CH3
O
OH
O
+
OEt
[H ], EtOH, -H2O
1) SOCl2
2) EtOH
21.23.
a)
OH
1) NaOH
2) CH3
O
Na2Cr2O7
[H+], EtOH, -H2O
OH
O
OEt
H2SO4, H2O
1) SOCl2
2) EtOH
b)
1) NaOH
2) CH3
O
Na2Cr2O7
[H+], EtOH, -H2O
OH
H2SO4, H2O
1) SOCl2
2) EtOH
21.24.
O
1) xs LAH
OMe
a)
O
OH
+
MeOH
OH
+
MeOH
1) xs EtMgBr
OMe
b)
2) H2O
2) H2O
O
O
c)
1) xs LAH
2) H2O
HO
OH
O
OEt
526
CHAPTER 21
O
O
H3O
OEt
+
OH
+ EtOH
d)
O
O
1) NaOH
OH
O
2) Et
e)
O
1) xs EtMgBr
O
OH
2) H2O
f)
OH
21.25.
H
H
O
H O
O
O
H
H
H O H
O
O
HO
H
O
H O H
OH
HO
O
H
O
HO
H
H O H
OH
O
HO
OH
21.26.
O
1) excess LAH
NH2
a)
O
Cl
NH2
2) H2O
O
excess
NH3
NH2
+ NH4Cl
b)
O
O
NH2
c)
H3O
+
heat
OH
+ NH4
HO
OH H
O
H
O
H
527
CHAPTER 21
21.27.
O
Cl
1) excess NH3
NH2
2) LAH
3) H2O
21.28.
a)
H
O
H
H
O
H O
N
H
H
H
N
H O H
O
HO
H
H
H O H
N
HO
OH H
N
H
O
H2N
H
H O H
OH
H2N
O
HO
OH
b)
O
H
N
OH
O
O
H
N
H
O H
H
O
H2N
OH H
N
OH
O
O
H2N
O
H
H
O
OH H
N
H
H
528
CHAPTER 21
21.29.
CN
1) xs LAH
NH2
2) H2O
a)
Br
1) NaCN
O
2) MeMgBr
3) H3O
b)
+
O
CN
c)
OH
1) EtMgBr
1) LAH
2) H2O
2) H2O
O
CN
H3O
+
OH
d)
21.30.
a)
O
Cl
1) excess NH3
CN
2) SOCl2
b)
1) NaCN
2) H3O
+
OH
Br
O
1) Mg
2) CO2
+
3) H3O
CHAPTER 21
21.31.
H
H O
H O H
H
C N
N
C N H
H
O
H
H
H O H
H
N
H
H
N
O
H
H
H
O
OH
H O H
N
H
O
21.32.
O
OMe
a)
O
Cl
2) SOCl2
1) SOCl2
OH
2) excess NH3
NH2
3) LAH
4) H2O
b)
O
c)
O
1) H3O+
O
O
1) H2O
2) SOCl2
O
Cl
H
OH
H
H
H
N
529
530
CHAPTER 21
1) H3O+
O
2) SOCl2
OEt
NH2
3) excess NH3
4) LAH
5) H2O
d)
O
1) SOCl2
3) SOCl2
e)
O
f)
CN
2) excess NH3
OH
H 2O
O
O
O
OH
O
O
1) H2O
Cl
OEt
+
2) [H ], EtOH
g)
O
1) H3O
NH2
+
O
2) SOCl2
H
3) LiAl(OR)3H
4) H2O
h)
CN
1) H3O
+
OH
2) excess LAH
3) H2O
i)
1) Na2Cr2O7, H2SO4, H2O
OH
j)
2) SOCl2
3) excess NH3
CN
4) SOCl2
21.33. Four steps: 1) oxidize to a carboxylic acid, 2) convert into an acid halide, 3)
convert into an amide, and 4) reduce to give an amine.
531
CHAPTER 21
21.34.
1) BH3 THF
2) H2O2, NaOH
O
Cl
3) Na2Cr2O7, H2SO4, H2O
4) SOCl2
21.35.
OH
O
1) SOCl2
OH
2) Et2CuLi
3) LAH
4) H2O
a)
1) Mg
H
Br
2)
O
O
H
O
3) H2O
O
4)
Cl
b)
CN
O
1) H3O+
2) SOCl2
O
3) excess MeMgBr
O
4)
Cl
c)
21.36.
O
SOCl2
NH2
C
N
1) EtMgBr
2) H3O
+
O
[H+]
(CH3)2NH
-H2O
N
532
CHAPTER 21
21.37.
a)
1) SOCl2
2) LiAl(OR)3H
3) H2O
H3O+
O
CH3CN
1) xs LAH
OH
PBr3
2) H2O
OH
Br
1) Mg
O
2)
H
3) H2O
OH
b)
H3O+
O
CH3CN
1) xs LAH
PBr3
2) H2O
OH
OH
Br
1) Mg
Mg
2) CO2
3) H3O+
1) EtMgBr
OH
1) SOCl2
H
2) H2O
OH
2) LiAl(OR)3H
O
O
c)
1) SOCl2
2) LiAl(OR)3H
3) H2O
H3O+
CH3CN
O
1) xs LAH
OH
PBr3
2) H2O
OH
1) SOCl2
2) xs EtMgBr
3) H2O
Br
1) Mg
O
2)
Mg
H
3) H2O
OH
1) xs EtMgBr
2) H2O
O
Na2Cr2O7
H2SO4, H2O
OH
533
CHAPTER 21
d)
H3O+
O
CH3CN
1) xs LAH
PBr3
2) H2O
OH
OH
Br
1) Mg
Mg
2) CO2
3) H3O+
1) xs EtMgBr
2) H2O
OH
SOCl2
Cl
O
OH
O
21.38. The signal at 1740 cm-1 indicates that the carbonyl group is not conjugated with
the aromatic ring (it would be at a lower wavenumber if it was conjugated),
O
O
OH
1) LAH
OH
2) H2O
21.39.
a)
Increasing acidity
COOH
O
COOH
COOH
Br
H3C
O 2N
O
b)
Increasing acidity
Br
O
Br
OH
O
COOH
COOH
O
OH
OH
Br
534
CHAPTER 21
21.40.
a) The second carboxylic acid moiety is electron withdrawing, and stabilizes the
conjugate base that is formed when the first proton is removed.
b) The carboxylate ion is electron rich and it destabilizes the conjugate base that
is formed when the second proton is removed.
O
O
O
O .
c)
d) The number of methylene groups (CH2) separating the carboxylic acid
moieties is greater in succinic acid than in malonic acid. Therefore, the
inductive effects are not as strong.
21.41.
a) cyclopentanecarboxylic acid
b) cyclopentanecarboxamide
c) benzoyl chloride
d) ethyl acetate
e) hexanoic acid
f) pentanoyl chloride
g) hexanamide
21.42.
a) acetic anhydride
b) benzoic acid
c) formic acid
d) oxalic acid
21.43.
chirality centers
O
O
OH
O
OH
OH
hexanoic acid
3-methylpentanoic acid
2-methylpentanoic acid
O
O
OH
4-methylpentanoic acid
O
OH
OH
2,2-dimethylbutanoic acid
O
2,3-dimethylbutanoic acid
O
OH
OH
3,3-dimethylbutanoic acid
2-ethylbutanoic acid
CHAPTER 21
535
21.44.
O
O
Cl
Cl
butanoyl chloride
2-methylpropanoyl chloride
21.45.
O
1) excess LAH
OH
a)
2) H2O
OH
1) excess LAH
O
2) H2O
OH
b)
3) TsCl, py
4) t-BuOK
1) excess LAH
O
2) H2O
OH
c)
OH
3) PBr3
4) NaCN
5) H3O+
O
21.46.
O
1) BH3 THF
2) H2O2, NaOH
3) Na2Cr2O7, H2SO4, H2O
a)
Br
b)
OH
1) NaCN
2) H3O+
O
OH
21.47. As discussed in Chapter 19, the methoxy group is electron donating via
resonance, but electron withdrawing via induction. The resonance effect is stronger, but
only occurs when the methoxy group is in an ortho or para position.
536
CHAPTER 21
21.48.
O
a)
N
H
b)
OH
O
O
c)
O
OH
d)
O
O
O
e)
O
NH2
f)
O
g)
OH
h)
21.49.
O
O
Cl
a)
ONa
OH
b)
c)
a)
1) xs LAH
OH
2) H2O
O
d)
21.50.
O
O
OH
CHAPTER 21
O
O
1) SOCl2
OH
b)
O
SOCl2
O
1) H3O
OMe
d)
N
C
NH2
c)
N
2) (CH3)2NH,
pyridine
+
O
O
O
2) CH3COCl,
pyridine
O
O
DIBAH
OMe
H
e)
O
OH
O
O
O
O
+
HO
O
f)
O
O
H
N
N
Cl
pyridine
g)
O
1) xs LAH
O
HO
OH
2) H2O
h)
O
O
N
H3O+
heat
N
OH
H
i)
O
O
j)
O
H3O
+
OH
OH
537
538
CHAPTER 21
21.51.
O
+
HO
OH
a)
O
+
OH
b)
HO
c) CH3CH2CO2H + (CH3)3COH
21.52.
OH
Na2Cr2O7
H2SO4, H2O
O
[H+]
O
OEt
EtOH
OH
DIBAH
SOCl2
O
1) LiAl(OR)3H
O
H
2) H2O
Cl
xs NH3
O
NH2
21.53.
a) NaOH, followed by Na2Cr2O7, H2SO4, H2O
b) NaCN followed by H3O+
c) NaOH, followed by Na2Cr2O7, H2SO4, H2O, followed by SOCl2
d) NaCN, followed by H3O+, followed by SOCl2, followed by xs NH3
e) NaOH, followed by Na2Cr2O7, H2SO4, H2O, followed by SOCl2, followed by xs NH3
f) NaCN followed by H3O+, followed by [H+], EtOH (with removal of water)
CHAPTER 21
21.54.
OH
1) Br2, AlBr3
2) Mg
O
3)
4) H2O
a)
1) Br2, AlBr3
O
2) Mg
N
3) CO2
4) H3O+
5) SOCl2
6) excess (CH3)2NH
b)
1) (CH3)2CHCl, AlCl3
OH
2) NBS, heat
O
3) Mg
4) CO2
5) H3O
c)
+
H
N
1) Cl2, AlCl3
2) NaNH2, NH3
3)
O
O
, pyridine
Cl
d)
21.55.
O
Br
1) Mg
2) CO2
a)
3) Et
O
539
540
CHAPTER 21
OH
O
1) Na2Cr2O7, H2SO4, H2O
2) SOCl2
3) Et2CuLi
b)
O
Br
1) Mg
2) CO2
3) H3O+
O
1) LAH
N
H
2) H2O
O
3)
N
Cl
4) SOCl2
5) excess CH3NH2
c)
Br
1) NaCN
O
2) EtMgBr
d)
3) H3O+
21.56. A methoxy group is electron donating, thereby decreasing the electrophilicity of
the ester moiety. A nitro group is electron withdrawing, thereby increasing the
electrophilicity of the ester group.
21.57.
541
CHAPTER 21
21.58.
1) Mg
Br
O
2) CO2
3) H3O
N
+
4) SOCl2
5) excess Et2NH
21.59.
O
O
OH
1) excess MeMgBr
+
2) H3O+
O
OH
21.60.
H
H O
H
O
O
OH
H
OH
H O H
OH
OH
H
O
H
OH
H O H
OH
H
O
H
O
H O H
OH
H
H
O
H
OH
O
OH
H
H
H
O
H O H
O H
H
O
O
H
O
H
O
O H
H
542
CHAPTER 21
21.61.
a)
O
Cl
O
H O R
Cl
Cl
H
O
- Cl
Cl
O
Cl R
O
R
H
H O R
- Cl
O
H
O
H
OR
O
R
OR
O
Cl
R
Cl
H O R
O
OR
RO
O
O
O
b)
OH
Ph
c)
Ph
Ph
21.62.
N
N
N
a)
S
OH
CF3
HO
b)
O
H O R
O
decanoic acid
OR
CHAPTER 21
21.63.
1) Br2, AlBr3
2) Mg
O
O
3)
H
H
O
O
4)
Cl
21.64.
H
N
HO
NH2 O
H
HO
O
OH
O
phenylalanine
aspartic acid
21.65.
a)
O
Ph
O
Cl
H O Ph
Ph
O
H
- Cl
O
Cl Ph
Ph
O
Ph
H
N
O
Ph
b)
O
O
O
OH
OH
OH
O
H O
H
O H
H
O
HO
O
O
O
O
OH
O
Ph
543
544
CHAPTER 21
c)
O
O
O
OH
O
H
OH
O
O
O
H
O H
H
OH
OH
OH
O
O
O
d)
O
H2N NH2
Cl
Cl
O
H
O Cl
N
N
H
H H
Cl
O
O
- Cl
N
H
H
N
H
H
Cl
O
N
O
O
O
H
N
N H
H
N
O
N
N
O
H
H
H
N
N H
O Cl H
O
N
H
Cl
O
H
N
H
CHAPTER 21
e)
H H
C C H
H H
O
O
O
O
O
O
H H
H C C
H H
H
O
O
H
HO
O
O
H
O
H
HO
HO
21.66. The three chlorine atoms withdraw electron density via induction. This effect
renders the carbonyl group more electrophilic.
21.67.
OH
H3O+
O
O
+ CO2
heat
O
OH
21.68
NH2 H
N
O
S
N
O
a)
b) Ampicillin
O
OH
545
546
CHAPTER 21
21.69.
OH
HO
O
(glycolic acid)
hydroxyacetic acid
21.70.
O
O
O
O
O
O
O
O
21.71.
O
Cl
O
+
Cl
H2N
NH2
21.72.
O
O
HO
HO
Cl
HO
Cl
O
Cl H
O
HO
Cl
O
O
O
Cl
O
O
Polymer
HO
Cl
O
H
Cl
O
CHAPTER 21
21.73.
O
1) SOCl2
O
O
2) Et2CuLi
OH
3) HOCH2CH2OH,
+
[H ], -H2O
a)
1) H3O+
O
2) SOCl2
3) LiAl(OR)3H
NH2
N
4) H2O
5) [H+], CH3NH2, -H2O
b)
1) MCPBA
O
2) H3O
O
+
3) SOCl2
N
4) (CH3)2NH
c)
O
1) H3O
OMe
+
S
S
H
2) SOCl2
3) LiAl(OR)3H
+
4) HSCH2CH2SH, [H ], -H2O
d)
1) SOCl2
COOH
e)
2) LiAl(OR)3H
O
3) HOCH2CH2OH,
+
[H ], -H2O
O
OH
1) Na2Cr2O7, H2SO4, H2O
OH
3) H3O
f)
O
O
g)
O
2) MCPBA
+
1) excess LAH
O
2) H2O
O
3)
O
+
[H ], -H2O
547
548
CHAPTER 21
21.74.
O
OH
Cl
O
OH
O
1) Cl2, AlCl3
1) NaOH
2) HNO3, H2SO4
2) HCl, Zn
NH2
NO2
H
N
O
21.75.
H
H O
O
O
O
H
H
O
O
O
OH
OH O
O
OH
OH
H
H
H
O H
H
O
OH O
H
O
H
-
H
OH O
O
OH
H
O
O
H
H
O
O
H
OH O
O
OH
H
OH
O
H
H O
OH O
HO
H
OH
OH O
HO
HO OH
H
O H
OH
HO
H
H
O
O
HO
H
O
HO
H
O
O
HO
H
OH
H O
O
H
O H
H
HO OH
O
HO
O
H
549
CHAPTER 21
21.76.
O
O
xs NH3
Cl
NH2
Compound A
21.77.
O
O
O
O
21.78. An IR spectrum of butyric acid should have a broad signal between 2500 cm-1 and
3600 cm-1. An IR spectrum of ethyl acetate will not have this signal.
21.79. The 1H NMR spectrum of para-chlorobenzaldehyde should have a signal at
approximately 10 ppm corresponding to the aldehydic proton. The 1H NMR
spectrum of benzoyl chloride should not have a signal near 10 ppm.
21.80.
O
MeO
OH
21.81. If the oxygen atom of the OH group in the starting material is an isotopic label,
then we would expect the label to be incorporated into the ring of the product:
O
H O S O H
O
O
O
HO
O
HO
O
O
HO
O
OH
O
O S O H
O
O
R
OH
R
HO
O
R
O
H O S O H
O
H
O
R
O
HO
O
R
R
O
H
O
R
H
H
O
O
O S O H
O
HO
O
O
R
550
CHAPTER 21
21.82. The lone pair of the nitrogen atom in this case is participating in resonance and is
less available to donate electron density to the carbonyl group. As a result, the carbonyl
group is more electrophilic than the carbonyl group of a regular amide (where the lone
pair contributes significant electron density to the carbonyl group). Also, when this
compound functions as an electrophile in a nucleophilic acyl substitution reaction, the
leaving group is particularly stable because it is an aromatic anion. With a good leaving
group, this compound more closely resembles the reactivity of an acid halide than an
amide.
21.83.
a) DMF, like most amides, exhibits restricted rotation about the bond between the
carbonyl group and the nitrogen atom. This restricted rotation causes the methyl groups
to be in different electronic environments. They are not chemically equivalent, and will
therefore produce two different signals (in addition to the signal from the other proton in
the compound). Upon treatment with excess LAH followed by water, DMF is reduced to
an amine that does not exhibit restricted rotation. As such, the methyl groups are now
chemically equivalent and will together produce only one signal.
b) Restricted rotation causes the methyl groups to be in different electronic environments.
As a result, the 13C NMR spectrum of DMF should have three signals.