Direct synthesis of nitriles from alcohols or aldehydes using H 5IO 6/KI in aqueous ammonia

Article abstract of DOI:10.1080/00397911.2011.591035

The oxidative conversion of alcohols or aldehydes to the corresponding nitriles in moderate to good yields was easily achieved by treatment of H ₅IO₆ and KI in aqueous NH₃. This simple and one-pot system provides easy workup and separation of the product. Copyright

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Direct Synthesis of Nitriles from Alcohols
or Aldehydes Using H IO /KI in Aqueous
5
6
Ammonia
a
b
Arash Ghorbani-Choghamarani , Mohammad Ali Zolfigol , Maryam
b
a
Hajjami & Sara Sardari
a
Department of Chemistry, Faculty of Science, Ilam University, Ilam,
Iran
b
Faculty of Chemistry, Bu-Ali Sina University, Hamadan, Iran
Accepted author version posted online: 20 Jan 2012.Version of
record first published: 05 Sep 2012.
To cite this article: Arash Ghorbani-Choghamarani, Mohammad Ali Zolfigol, Maryam Hajjami & Sara
Sardari (2013): Direct Synthesis of Nitriles from Alcohols or Aldehydes Using H IO /KI in Aqueous
5
6
Ammonia, Synthetic Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 43:1, 52-58
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1
Synthetic Communications , 43: 52–58, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.591035
DIRECT SYNTHESIS OF NITRILES FROM ALCOHOLS OR
ALDEHYDES USING H IO /KI IN AQUEOUS AMMONIA
5
6
1
Arash Ghorbani-Choghamarani, Mohammad Ali Zolfigol,
2
2
Maryam Hajjami, and Sara Sardari
1
1
Department of Chemistry, Faculty of Science, Ilam University, Ilam, Iran
Faculty of Chemistry, Bu-Ali Sina University, Hamadan, Iran
2
GRAPHICAL ABSTRACT
Abstract The oxidative conversion of alcohols or aldehydes to the corresponding nitriles in
5 6 3
moderate to good yields was easily achieved by treatment of H IO and KI in aqueous NH .
This simple and one-pot system provides easy workup and separation of the product.
Keywords Alcohol; aldehyde; ammonia; nitrile; periodic acid; potassium iodide
INTRODUCTION
Nitriles are useful functional groups in synthetic organic chemistry. Organic
nitriles are versatile synthetic intermediates that can easily be converted into a var-
[1]
iety of other functional groups. Hydrolysis of nitriles is useful for the production of
hydroxy analogs of methionine derivatives that could have an interest in cattle feed-
ing and for the transformation of compounds containing other acid- or base-
[
2]
[3]
sensitive groups. Nitrile groups are of interest in the cyclopropanation process.
This group is a facilitator for electron-transfer chain-substitution processes.
[
4]
Several methods are known for the synthesis of nitriles. The most common and
well-known procedure for the preparation of nitriles is the nucleophilic displacement
[
of substrates with suitable leaving groups such as halogen compounds. The other
5]
[
6,7]
reported methods are dehydration of amides or aldoximes,
[10]
conversion of alde-
into nitriles using various reagents, and
[
8]
[9]
hydes, alcohols, or carboxylic acids
the direct conversion of amines into nitriles.
often suffer from several drawbacks such as tedious workup procedure, poor yields
[
11]
Some of these reported procedures
Received January 20, 2011.
Address correspondence to Arash Ghorbani-Choghamarani, Department of Chemistry, Faculty of
Science, Ilam University, Ilam, Iran. E-mail: arashghch58@yahoo.com, a.ghorbani@mail.ilam.ac.ir
5
2

DIRECT SYNTHESIS OF NITRILES
53
of products, and expensive reagents and catalysts. To overcome these limitations,
oxidative methods involving the direct conversion of aldehydes and alcohols to
the nitriles using commercially available aqueous ammonia could be a viable alter-
native and clean route. Ammonia is one of the most attractive sources of nitrogen
[
12]
for the synthesis because of its low cost and wide availability. The oxidative syn-
thesis directly from alcohols or aldehydes with NH as a nitrogen source is a good
3
[
13]
candidate for the ‘‘green nitrile synthesis.’’
from alcohols) is very difficult and reported procedures (such as I =NH , o-iod-
However, direct synthesis (especially
[
8]
2
3
[
14]
[15]
[16]
oxybenzoic acid=NH3,
require the use of toxic and expensive reagents and catalysts.
Ru(OH) =Al O =NH ,
KI=I -TBHP=NH ,
3
etc.)
x
2
3
3
2
Therefore, as a part of our studies we became interested in a new, simple, and
facile protocol for the direct conversion of alcohols and aldehydes to the correspond-
ing nitriles using periodic acid (H IO ) and potassium iodide (KI) in aqueous
5
6
ꢀ
ammonia at 60 C.
RESULTS AND DISCUSSION
In continuation of our ongoing program on the functionalization of organic com-
pounds, we decided to design a new oxidative system for the direct conversion of
aldehydes and alcohols to the nitriles. In this light, a variety of aromatic or aliphatic
aldehydes and alcohols (Scheme 1) were transformed into nitriles smoothly via reaction
with aqueous ammonia in the presence of periodic acid (H IO ) and potassium iodide
5
6
ꢀ
(
KI) at 60 C. The results of these transformations are summarized in Table 1.
Scheme 1. Oxidative conversion of alcohols and aldehydes into corresponding nitriles.

54
A. GHORBANI-CHOGHAMARANI ET AL.
Table 1. Oxidative conversion of aldehydes (a) and alcohols (b) to the corresponding nitriles with H
ꢀ
5
IO
6
=
a
KI in aqueous NH
3
at 60 C
b
ꢀ
ꢀ
Entry
Substrate
Time (min)
Yield (%)
97
c,d
52
Mp ( C) (observed)
Mp ( C) (reported)
Ref.
1
2
3
4
5
6
7
8
9
1a
1a
1a
2a
3a
4a
5a
6a
7a
8a
9a
10a
11a
12a
1b
2b
3b
4b
4b
5b
6b
7b
8b
9b
9b
90
90
58–61
—
—
59
—
[17]
—
e
180
90
No reaction
—
94
—
97
93
60
99
92
78
80
92
88
73
78
93.5–94.5
113–115
36–37.7
26–28
68.3–70.6
Oil
[17]
[14]
[14]
90
90
110–111
33–35
25
90
90
[13a]
[18]
[14]
[19]
[19]
[20]
[14]
[21a]
[14]
[19]
[7a]
[20]
[20]
[21b]
[21c]
[22]
[21d]
[17]
—
62.5
Oil
60
30
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
106–108
110–112
65–67
Oil
104–106
112
90
90
65–66
Oil
Oil
90
90
Oil
f
180
180
180
180
180
180
180
180
180
180
180
75
112–115
59–61
41–43
147–149
147–149
Oil
110–111
55–58
42
g
55
50
f
f
70
e,f
20
149–150
149–150
Oil
g
76
g
70
Oil
51–53
Oil
Oil
47
g
45
g
11
88
Oil
59
f
58–59
—
c,d
16
—
a
b
c
Aldehyde=H IO
Isolated yield.
5
6
=KI ¼ 1:2:0.05; alcohol=H
5
IO
6
=KI ¼ 1:3:0.8.
In the absence of KI.
d
1
Yield determined by H NMR.
Reaction performed at room temperature.
e
f
Yield determined by preparative TLC.
GC yield.
g
All nitrile synthetic reactions were performed in a sealed tube and conver-
sion of aldehydes and alcohols was indicated by thin-layer chromatography
TLC).
To investigate the role of potassium iodide (KI), 4-methoxybenzaldehyde, and
-methoxybenzyl alcohol (as a representative samples) were subjected to the oxidat-
(
4
ive conversion to the corresponding nitrile in the absence of KI. Surprisingly the
reactions did not complete (Scheme 2, entries 2 and 25, Table 1).
Also, the effect of temperature in outcome of reaction was examined via doing
reaction in the ambient temperature. As can be seen from Table 1 (entries 3 and 20),
the temperature is necessary for both conversion of aldehydes and alcohols into
nitriles. This result is outlined in Scheme 3.
A proposed mechanism for these transformations is outlined in Scheme 4. In
the case of alcohol, formation of aldehyde could be an intermediate, which can be

DIRECT SYNTHESIS OF NITRILES
55
Scheme 2. Conversion of 4-methoxybenzaldehyde and 4-methoxybenzyl alcohol into 4-methoxybenzonitrile
in the absence of KI.
Scheme 3. Influence of temperature on the synthesis of nitriles.
achieved via oxidation of alcohol by H IO and KI. In the next step aldehyde reacts
5
6
with ammonia to form an imine, which further reacts with iodine (that formed from
H IO =KI) to form N-iodo aldimine, which eventually oxidized into corresponding
nitrile.
5
6

56
A. GHORBANI-CHOGHAMARANI ET AL.
Scheme 4. Mechanism of the conversion of alcohols and aldehydes into nitriles.
CONCLUSION
In summary, a simple and convenient protocol has been delineated for the
direct conversion of alcohols and aldehydes to their corresponding nitriles using
KI in combination with H IO in aqueous ammonia. The present method is mild,
5
6
gives moderate to good yields of nitriles, and avoids the use of expensive and toxic
metal catalysts and reagents. Moreover, the present nontransition metallic system
also provides an easy scale-up and separation protocol.
EXPERIMENTAL
Chemicals were purchased from Fluka, Merck, and Aldrich chemical compa-
nies. The nitrile products were characterized by comparison of their spectral (IR,
1
13
H NMR, and C NMR) and physical data with authentic samples.
Conversion of 4-Methoxybenzylaldehyde to the
4-Methoxybenzonitrile
H IO (455.8 mg, 2 mmol) and KI (8.3 mg, 0.05 mmol) were added to a mixture
5
6
of 4-methoxybenzaldehyde (136 mg, 1 mmol) and aqueous NH (3 mL) at room
3
ꢀ
temperature. The resulting mixture was stirred in sealed tube at 60 C. After
90 min, the reaction mixture was cooled down to room temperature diluted with
water, and Na S O (5 mmol) was added. Finally, the product was extracted with
2
2
3
dichloromethane (20 mL), and the organic phase was dried over Na SO (3 g) to give
2
4
4
-methoxybenzonitrile in 97% yield.

DIRECT SYNTHESIS OF NITRILES
57
Oxidation of 4-Bromobenzylalcohol to 4-Bromobenzonitrile
In a sealed tube a suspension of 4-bromobenzylalcohol (171 mg, 1 mmol),
H IO (683.7 mg, 3 mmol), and KI (132.8 mg, 0.8 mmol) in aqueous ammonia
5
6
ꢀ
(3 mL) was stirred at 60 C. After 180 min, the reaction mixture cooled down to room
temperature and was diluted with water, and Na S O (5 mmol) was added. Then
2
2
3
product was extracted with dichloromethane (20 mL), and the organic phase was
dried over Na SO (3 g). Finally the obtained residue was purified by preparative
TLC to afford pure 4-bromobenzonitrile in 75% yield.
2
4
ACKNOWLEDGMENTS
The authors acknowledge Bu-Ali Sina University Research Council (Grant
Number 32-1716), Center of Excellence in Development of Chemical Methods
(CEDCM), National Foundation of Elites (BMN), and Ilam University, Ilam, Iran
for financial support of this work.
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