Sodium azide as a catalyst for the hydration of nitriles to primary amides in water

Article abstract of DOI:10.3184/174751915X14296361042516

The selective conversion of aromatic nitriles to primary amides has been accomplished using sodium azide. The corresponding amides were obtained efficiently in excellent yields. This reaction was carried out under eco-friendly conditions using water in the absence of organic solvents.

Full text of DOI:10.3184/174751915X14296361042516

JOURNAL OF CHEMICAL RESEARCH 2015
VOL. 39 MAY, 267–269
RESEARCH PAPER 267
Sodium azide as a catalyst for the hydration of nitriles to primary amides in
water
a,b
a
a
Kiumars Bahrami *, Mohammad Mehdi Khodaei and Mohsen Roostaei
a
Department of Chemistry, Razi University, Kermanshah 67149-67346, Iran
b
Nanoscience and Nanotechnology Research Center (NNRC), Razi University, Kermanshah, 67149-67346, Iran
The selective conversion of aromatic nitriles to primary amides has been accomplished using sodium azide. The corresponding amides
were obtained efficiently in excellent yields. This reaction was carried out under eco-friendly conditions using water in the absence of
organic solvents.
Keywords: hydration, aromatic nitriles, sodium azide, primary amides
The success of organic reactions depends on functional group
transformations. Among functional groups, amides have great
significance. The hydration of nitriles to the corresponding
amides is very important in view of their broad industrial
To optimise the reaction conditions, the reaction of
benzonitrile and NaN was selected as a model at different
3
reaction temperatures (25, 50, 70 and 90 °C). The results
were evaluated qualitatively through TLC. The best result was
achieved by carrying out the reaction with 1:0.1 mole ratios of
1-3
and pharmacological applications, Commonly, this reaction
4
5
is carried out using strong acid or base methods that often
cause further hydrolysis of the amides into the corresponding
carboxylic acids. Although other methods to overcome this
aromatic nitrile, and NaN at 90 °C for 2 hours in water (Table 1,
3
entry 4). No reactions have been observed at room temperature
and reactions run at 70 °C gave only a low yield. On the other
hand, blank experiments without azide ion were carried out by
keeping benzonitrile in water in the temperature range 50–90 °C
for 6 hours. In all cases, the nitrile was quantitatively recovered
(Table 1, entry 1). Thus, the use of azide ion is essential for the
success of the reaction.
6
-19
limitation have been investigated,
attention is moving
towards newer methods that perform the selective conversion of
nitriles to amides.
However, in spite of their potential utility, some of these
methods involve drawbacks such as the use of hazardous,
expensive or less easily available catalysts or reagents, harsh
conditions, the further hydrolysis to carboxylic acids, undesired
side reactions occurring on other functional groups, and the
requirement to use organic solvents. Therefore, the discovery of
milder and practical routes for the synthesis of amides is highly
desirable.
Using the optimised reaction conditions, a series of aryl
amides was prepared from various aromatic, benzylic, and
heteroaromatic nitriles (Table 2). Substrates with electron-
withdrawing groups gave better results than those without
such groups, indicating that the electrophilicity of the nitrile
is important. Arylacetonitriles were smoothly converted to
the desired amides in excellent yields (Table 2, entries 7–10).
The reaction of 2-chlorobenzonitrile is sluggish compared
to that of 4-chlorobenzonitrile due to the sterically crowded
nitrile group (Table 2, entries 4 and 5). The preparation of
4-cyanobenzamide from 1,4-dicyanobenzene is of great
interest, because, the remaining cyano group can be converted
to other functional groups (Table 2, entry 6). However, none
of the other products showed any contamination with acid.
In developing environmentally benign and economical
syntheses, the avoidance of the use of harmful organic solvents
is important. An attractive alternative is the use of water. In
addition, reactions in aqueous media often permit unique
reactivities and selectivities that are not usually observed in
2
0,21
organic media.
reactions in water,
In continuation of our interest in organic
2
2-24
we now report the unexpected formation
of amides from the reaction of aromatic nitriles with NaN in
3
1
water.
The structures of the products were confirmed by their H
2
5
Das’s group has reported the reactions of organic nitriles
NMR data. Currently, a limitation of the present reaction is
the inapplicability to aliphatic nitriles. It was found that the
reaction of 1-butyronitrile, an aliphatic nitrile, did not proceed
at all after 24 h. In this type of aliphatic nitrile, the nitrile group
is less electrophilic than that of an aromatic nitrile.
with NaN in the presence of silica-supported sodium hydrogen
3
2
5
sulfate (NaHSO .SiO ), in DMF under reflux. These reactions
4
2
afforded the corresponding 5-substituted 1H-tetrazoles in high
yields. When we carried out the reactions of aromatic nitriles
with NaN in pure water, to our surprise, no 5-substituted
The proposed mechanism for the conversion of nitrile to their
corresponding amides is shown in Scheme 2. The first step
3
1H-tetrazoles were observed, and instead, the desired amides
were produced in moderate to excellent yields (Scheme 1).
However, to the best of our knowledge, the hydrolysis of nitriles
to primary amides promoted by azides has not been previously
reported in cyclisation studies.
a
Table 1 Effect of increasing amount of NaN on hydration of benzonitrile
3
O
C
N
NH2
b
O
Entry
NaN /mmol
Yield/%
3
NaN3
c
1
0
0
R
C
N
R
C
NH2
2
3
4
0.05
0.08
0.1
50
75
91
H O, 90 °C
2
R=Aryl, benzyl
a
Scheme 1 Amides from nitriles.
Reaction conditions: the reactions were performed with benzonitrile (1 mmol)) for 2
hours at 90 °C with H O as solvent.
Isolated yield.
2
b
c
This reaction was carried out at temperatures of 50, 70 and 90 °C. In all cases,
*
Correspondent. E-mail: kbahrami2@hotmail.com
benzonitrile was quantitatively recovered.

2
68 JOURNAL OF CHEMICAL RESEARCH 2015
a
Table 2 Synthesis of amides from nitriles
O
C
R
CN
R
NH2
b
Entry
Amide
Yield/% (Time/h)
M.p./°C
Lit. m.p./°C
2
6
1
2
3
4
5
6
7
8
9
C H CONH
91 (2)
90 (3)
91 (0.4)
95 (0.5)
93 (1)
91 (0.5)
92 (9)
91 (1)
133–135
155–159
199–202
175–177
140–142
219–221
153–155
126–128
182–185
193–195
124–127
153–155
130
159–160
200–202
178–179
142
218–221
6
5
2
2
7
4-MeC H CONH
2
6
4
2
8
4-O NC H CONH
2
6
4
2
2
9
4-ClC H CONH
6
4
2
3
0
2-ClC H CONH
6
4
2
3
1
7
2
3
4-NCC H CONH
6
4
2
2
C H CH CONH
2
155–157
6
5
2
3
2-MeOC H CH CONH
2
124–125
183–185
6
4
2
3
4-ClC H CH CONH
2
90 (8)
91 (7)
91 (2)
6
4
2
3
4
1
0
4-O NC H CH CONH
191
2
6
4
2
2
2
6
1
1
3-PyridylCONH2
4-PyridylCONH2
129–130
154–160
3
5
1
2
93 (1)
a
b
1
The purified products were characterised by m.p. and H NMR.
Yields refer to pure isolated products.
mentioned in Table 1. After completion of the reaction (monitored
by TLC), the reaction mixture was cooled and the precipitated-out
solid was filtered and washed with water (3 × 5 mL) to give the pure
product. The products were identified by their H NMR spectra and
their physical data (m.p.) were compared with those described in the
literature. Spectral data for the selected compound are as follows.
N
N
N
N
Ar
C
N
N
Ar C
1
N
N
N
2
7
4
-Methylbenzamide: White solid; m.p. 155–159 °C (lit. 159–160
1
NH
H2O
OH
OH
°
C); H NMR (200 MHz, DMSO-d ): δ = 2.36 (3H, s), 6.76 (1H, br),
6
Ar
Ar
C
Ar
C
7
.18 (2H, d, J = 6.2 Hz), 7.57 (1H, br), 7.78 (2H, d, J = 6.2 Hz).
-
30
2
-Chlorobenzamide: White solid; m.p. 140–142 °C (lit. 142 °C);
N
N
N
N
N
N
1
H NMR (200 MHz, DMSO-d ): δ = 6.42 (2H, br), 7.26–7.41 (3H, m),
6
7
.73–7.78 (2H, m),
2
H
32
-(2-Methoxyphenyl)acetamide: White solid; m.p. 126–128 °C (lit.
24–125 °C); H NMR (200 MHz, DMSO-d ): δ = 3.39 (3H, s), 3.78
OH
O
C
O
1
1
(
H2O
OH
6
2H, s), 5.96–6.99 (3H, m), 7.17–7.28 (3H, m).
C
NH
N
Ar
NH2
N
Ar
C NH2
-H2O
-HO
We are thankful to the Razi University Research Council for
partial support of this work.
N
N
N
N
-N3
Scheme 2 Proposed mechanism for the synthesis of amides.
Received 14 March 2015; accepted 17 April 2015
Paper 1503248 doi:10.3184/174751915X14296361042516
Published online:08 May 2015
involves the nucleophilic attack of azide ion on nitrile. This
makes the potential carbonyl carbon more electrophilic and
prone for the nucleophilc attack by giving it a greater partial
positive charge. The resulting intermediate is subsequently
hydrolysed to produce the amide with the liberation of azide
ion.
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