Iodine/aqueous NH4OAc: An improved reaction system for direct oxidative conversion of aldehydes and alcohols into nitriles

Article abstract of DOI:10.3184/030823408X283711

A convenient method for direct oxidative conversion of aldehydes and alcohols into nitriles has been developed by using the inexpensive and environmentally friendly reagent I₂/aqueous NH₄OAc. The aqueous NH₄OAc as a non-toxic cyanide source is more eco-friendly than aqueous ammonia, because gaseous ammonia evaporates easily from aqueous ammonia but not from aqueous NH₄OAc.

Full text of DOI:10.3184/030823408X283711

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18 RESEARCH PAPER
JANUARY, 18–19
JOURNAL OF CHEMICAL RESEARCH 2008
Iodine/aqueous NH4OAc: an improved reaction system for direct
oxidative conversion of aldehydes and alcohols into nitriles
Yi-Ming Ren, Yi-Zhong Zhu and Chun Cai*
Chemical Engineering College, Nanjing University of Science & Technology, Nanjing 210094, China
A convenient method for direct oxidative conversion of aldehydes and alcohols into nitriles has been developed by
using the inexpensive and environmentally friendly reagent I2/aqueous NH4OAc. The aqueous NH4OAc as a non-
toxic cyanide source is more eco-friendly than aqueous ammonia, because gaseous ammonia evaporates easily
from aqueous ammonia but not from aqueous NH4OAc.
Keywords: molecular iodine, cyanation, aldehydes, primary alcohols, oxidation, ammonium acetate
Nitriles are of considerable interest as the growth is present
in dyes, herbicides, natural products and pharmaceuticals.1,2
In addition, cyanides play a crucial role as they can be easily
converted into a variety of functional groups such as acids,
amides, ketones, oximes and amines.3
RCHO
I2/aq. NH4OAc
RCN
RCH2OH
Scheme 1 Iodine-mediated synthesis of nitriles in aq. NH4OAc.
Various methods for the synthesis of nitriles have been
reported. One of the most convenient methods is based on
the transition metal-mediated displacement of halides from
aromatic halides by the cyanide ion. Since the discovery of
transition metal-catalysed cross-coupling reactions, much
interest has been devoted to the development of a practical
version of this transformation.4,5 A number of successful
palladium-6-9 and nickel-catalysed10-12 protocols have been
reported. In addition, dehydration of aldoximes is a useful
method for the synthesis of nitriles.13 However, most of
the work has concentrated on the inconvenient traditional
sources of cyanide which have some severe drawbacks. Alkali
cyanides are highly poisonous, zinc cyanide leads to
stoichiometric waste of heavy metal salts and trimethylsilyl
cyanideissensitivetomoistureandcaneasilyliberatehydrogen
cyanide. This is also true for acetone cyanohydrin. The use of
aqueous ammonia or gaseous ammonia is also considered as
an expedient method for the transformation of aldehydes and
alcohols to their corresponding nitriles. Such as the system
of ammonia gas/I2/MeONa/MeOH,14 aqueous ammonia
/KI/MeONa/MeOH,15 ammonia gas/H2O2/CuCl/i-PrOH,16
aqueous ammonia /I2,17,18 etc. However, volatile ammonia has
an undesirable smell and is harmful to the environment. In
addition, ammonia is a common and undesirable contaminant
in waste water and biomass cultivation media and the
adverse effects of ammonia have promoted the development of
various techniques for its removal.19 Previously, NH2OH·HCl
has also been developed, as a good cyanide source for example
under microwave irradiation,20 in the system NH2OH·HCl/HY-
zeolite/m.w.,21 and in the system NH2OH·HCl/I2/DMSO.22
NH4OAc has drawn considerable attention as a good reagent
for various organic transformations.23-26 Following our
interest in cyanation,27-29 and as a part of our studies to explore
the utility of iodine-catalysed reactions,30-32 we decided to
investigate I2-mediated synthesis of nitriles by direct oxidative
conversion of aldehydes and alcohols using NH4OAc as the
nitrogen cyanide source (Scheme 1).
Table 1 Studies on the conversion of benzaldehyde into
benzonitrile by using iodine in aq. NH4OAc
I2/aq. NH4OAc
PhCN
PhCHO
30 min
Entry
1
I2/aq NH4Oac(eq/eq)
1.0/30
T/°C
25
Yield/%a
37
45b
54c
55
78
94
95
87
93
73
94
2
3
4
5
6
7
8
9
1.0/30
1.0/30
1.0/30
1.0/30
0.9/30
1.1/30
1.0/20
1.0/40
50
60
70
80
70
70
70
70
aIsolated yields.
bTHF (1 ml) was added.
cEtOH (1 ml) was added.
of I2 was 1.0 equivalent to benzaldehyde, and a reaction
temperature of 70°C was found to be appropriate (Table 1,
entry 4).
Under the optimised reaction conditions, we investigated
the direct oxidative conversion of aldehydes into nitriles
with I2/aq NH4OAc. The results are summarised in Table 2.
Table 2 showed that the aromatic aldehydes, having different
substituents such as chloro, nitro, methoxy, and methyl, were
converted into the corresponding nitriles in high yields in a
short time, and the reaction of aliphatic aldehydes also gave
the corresponding nitriles in high yields. However, a low yield
of p-hydroxybenzonitrile was obtained after 2 h (Table 2,
entry 8), perhaps because p-hydroxybenzaldehyde has a high
melting point and it remains in the solid state during the reaction.
We next examined the direct oxidative conversion of various
primary alcohols into nitriles with I2/aq NH4OAc (Table 3).
In each instance, the reaction was carried out at 100°C with
the given reaction time. As shown in Table 3, the primary
aromatic alcohols, having different substituents such as
chloro, nitro, methoxy, and methyl were converted into the
corresponding benzonitrile derivatives in high yields within
3 h. However, the reaction of aliphatic alcohols under the same
conditions only gave the corresponding nitriles in moderate
yields after 10 h. A higher yield of cyclohexanecarbonitrile
was obtained when more I2 was employed (Table 3, entry 7).
Firstly, the addition of 1.0 equivalent of molecular iodine
to a mixture of benzaldehyde and aq NH4OAc provided
benzonitrile in 37% yield at room temperature (Table 1, entry
1). We found that most of the iodine was not dissolved in
the aq. NH4OAc at room temperature, but the yield was not
increased greatly when THF or EtOH was employed (Table 1,
entry 1). We then found that iodine was completely dissolved
in aq NH4OAc when the reaction temperature was increased
to 50°C. From Table 1, we can see that the appropriate amount
* Correspondent. E-mail: c.cai@mail.njust.edu.cn
PAPER: 07/4945

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JOURNAL OF CHEMICAL RESEARCH 2008 19
I2/aq. NH4OAc
NH3
R
CH2OH
R
R
C
N
HI
N
(
)
HI
I2
(
)
O
C
I
H
C
I
I2
C
H
R
O
R
CH NH
(
)
(
)
(
)
HI
HI
H2O
R
H
H
Scheme 2 Plausible reaction pathway for nitrile
Table 2 Conversion of aldehydes into nitriles by using iodine
in aq. NH4OAc
Table 3 Conversion of primary alcohols into nitriles by using
iodine in aq. NH4OAc
Entry
RCHO
Reaction
time/min
Yield/%a
Entry
RCH2OH
Reaction time/h
Yield/%a
1
2
3
4
5
6
7
C6H5CH2OH
2
2
83
95
93
90
92
90
59
75b
64
65
56
1
2
C6H5CHO
25
20
25
30
20
25
30
120
30
25
25
15
20
30
30
15
94
96
95
92
97
90
91
54
92
92
95
86
87
90
87
90
4-NO2C6H4CH2OH
4-ClC6H4CH2OH
3-ClC6H4CH2OH
4-MeOC6H4CH2OH
4-MeC6H4CH2OH
c-C6H11CH2OH
4-NO2C6H4CHO
3-NO2C6H4CHO
2-NO2C6H4CHO
4-ClC6H4CHO
2
3
3
4
2
5
2
6
3-ClC6H4CHO
2-ClC6H4CHO
10
10
10
10
10
7
8
4-HOC6H4CHO
2-HOC6H4CHO
4-MeOC6H4CHO
4-MeC6H4CHO
2-Furaldehyde
3-Pyridinecarboxaldehyde
CH3CH2CHO
8
9
10
n-C7H15CH2OH
n-C5H11CH2OH
n-C3H7CH2OH
9
10
11
12
13
14
15
16
aIsolated yields.
bI2 (4.0 eq) was used.
References
CH3(CH2)2CHO
Cinnamaldehyde
1
2
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In conclusion, the present synthetic method is a simple,
inexpensive, effective and green synthesis of nitriles using
iodine in aq. NH4OAc. The advantages of the present reaction
are the elimination of metals, organic solvents and toxic
reagents, operational simplicity and the high yields of products.
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To a solution of aldehyde (1 mmol) and aq. NH4OAc (3 ml,
30 mmol) was added I2 (1 mmol) at room temperature. The mixture
was stirred at 70°C for an appropriate time (see Table 2) as required
for completion of the reaction. After the completion of the reaction,
the mixture obtained was treated with Na2S2O3 solution (5%).
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layer was dried and concentrated to provide the corresponding
product in an almost pure state. If necessary, the crude product was
purified by column chromatography on silica gel (EtOAc:petroleum
ether = 2:9) to afford the corresponding pure product.
Typical procedure for transformation of primary alcohols to
nitriles: To a solution of primary alcohol (1 mmol) and aq. NH4OAc
(3 ml, 30 mmol) was added I2 (3 mmol) at room temperature.
The mixture was stirred at 100°C for an appropriate time (see Table 3)
as required for completion of the reaction. After the completion of
the reaction, the mixture obtained was treated as above to afford the
corresponding pure product.
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Received 16 November 2007; accepted 14 January 2008
Paper 07/4945
doi: 10.3184/030823408X283711
PAPER: 07/4945