Selective aerobic hydrolysis of nitriles to amides using cobalt(II)/zinc

Article abstract of DOI:10.1007/s11164-014-1589-6

A novel protocol has been developed for the aerobic hydrolysis of nitriles to amides using cobalt(II)/zinc without using any strong acids and bases under solvent-free conditions. The reaction showed good performance for benzonitriles with sensitive groups such as ester and carboxylic acid.

Full text of DOI:10.1007/s11164-014-1589-6

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Res Chem Intermed
DOI 10.1007/s11164-014-1589-6
Selective aerobic hydrolysis of nitriles to amides
using cobalt(II)/zinc
•
Sajjad Keshipour Ahmad Shaabani
Received: 5 January 2014 / Accepted: 5 March 2014
Ó Springer Science+Business Media Dordrecht 2014
Abstract A novel protocol has been developed for the aerobic hydrolysis of
nitriles to amides using cobalt(II)/zinc without using any strong acids and bases
under solvent-free conditions. The reaction showed good performance for benzo-
nitriles with sensitive groups such as ester and carboxylic acid.
Keywords Nitrile hydrolysis Á Amide Á Aerobic Á Cobalt Á Zinc
Introduction
Amides are widespread in compounds of biological and pharmaceutical importance
[1]. Nitriles are a useful functional group that can be used for the preparation of
amides [2]. The hydrolysis of nitriles to the corresponding amides, as one of the
most fundamental reactions in organic synthesis, is troublesome and carboxylic acid
is usually produced as a by-product [3]. The classical method for the preparation of
amides from nitriles is hydrolysis using strong acids or bases, which exclude the
presence of most functional groups [3, 4]. For the hydrolysis with strong acids, the
selectivity was improved using cobalt complexes [5–8], but use of acids was a
drawback. The hydrolysis of nitriles can also be catalyzed with heterogeneous
catalysts [2, 9–12], such as metal oxides [13] and metals [14–17]. However, the
yields for most of them are low (\20 %). Recently, the application of metal
complexes as homogeneous catalysts in the hydrolysis of nitriles was introduced as
a much more effective approach [18–21]; however, the main problem is the low
Electronic supplementary material The online version of this article (doi:10.1007/s11164-014-1589-6)
contains supplementary material, which is available to authorized users.
S. Keshipour Á A. Shaabani (&)
Faculty of Chemistry, Shahid Beheshti University, G. C., P. O. Box 19396-4716, Tehran, Iran
e-mail: a-shaabani@sbu.ac.ir
123

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
S. Keshipour, A. Shaabani
selectivity of the reaction [22]. Other strategies toward the synthesis of amides
include the utilization of azides as amine equivalents in the modified Staudinger
reaction [23], hydrative amide syntheses with alkynes [24], and the thio acid/ester
ligation method [25]. Transition-metal-catalyzed carbonylation of alkenes [26],
alkynes [27], and haloarenes [28] with amines have also been employed for the
synthesis of amides. Finally, the direct utilization of aldehydes and alcohols under
oxidative conditions with amines can also serve as an attractive entry to amides [29–32].
In continuation of our efforts to introduce new and efficient strategies for various
aerobic organic transformations [33–37], here we report a new route including
‘‘aerobic hydrolysis of nitriles’’ promoted by Co(II)/Zn in the absence of strong
acids and bases.
Experimental
General
All reagents were purchased from Aldrich or Merck and used without further
purification. Melting points were measured on an Electrothermal 9,200 apparatus.
Identification and quantification were carried out on a Varian model 3,600 gas
chromatograph (Varian Iberica, Madrid, Spain) equipped with a split/splitless
capillary injection port and flame ionization detector (FID).
Typical procedure for the preparation of benzamide from phenylcyanide
in the presence of oxygen
The reaction was carried out in a 100-mL stainless steel autoclave. Phenylcyanide
(0.10 g, 1.00 mmol) was added to a mixture of ethylenediamine (0.12 g, 2.00 mmol),
CoCl2Á6H2O (0.24 g, 1.00 mmol) and Zn (0.07 g, 1.00 mmol) and the vessel was
placed in an autoclave. For some of the reactions that were carried out in solvent,
5 mL of solvent was also added. The autoclave was pressurized to 5.00 atm with O2.
The mixture was stirred in a preheated oil bath at 120 °C for 12 h. Then, the reaction
mixture was cooled to room temperature and the product was purified by column
chromatography on silica gel using n-hexane:CH2Cl2 (1:1) to give the benzamide
1
(88 % yield). Mp 125–127 °C; H NMR (CDCl3, 300 MHz) d = 6.26 (2H, br s,
NH2), 7.43-7.54 (3H, m, CH-Ar), 7.83 (2H, d, 3JHH = 7.6 Hz, CH-Ar).
Typical procedure for the preparation of benzamide from phenylcyanide using
H2O2
To a stirred solution of phenylcyanide (0.10 g, 1.00 mmol) in 10 mL H2O2 (30 %),
ethylenediamine (0.12 g, 2.00 mmol), CoCl2Á6H2O (0.24 g, 1.00 mmol) and Zn
(0.07 g, 1.00 mmol) were added and the vessel was stirred under appropriate
conditions (refluxing or at room temperature). After completion of the reaction, the
product was extracted from the mixture using CH2Cl2 (3 9 5 mL) and analyzed
with GC.
123

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Aerobic hydrolysis nitriles to amides using cobalt(II)/zinc
Table 1 Influence of the
Entry
Amount of (mol %)
Solvent
Yield (%)a
CoCl2Á6H2O, EDA, Zn and
solvent on the hydrolysis
CoCl2/EDA
Zn
1
20/200
100
100
100
100
100
100
0
–
Trace
48
71
88
89
91
0
2
50/200
–
3
75/200
–
4
100/200
150/200
200/200
100/200
100/200
100/200
100/0
–
5
–
6
–
7
–
8
50
–
49
72
54
77
83
80
53
75
9
75
–
10
11
12
13
14
15
100
100
100
100
100
100
–
Reaction conditions:
benzonitrile (1.00 mmol), O2
(5 atm), 120 °C, 12 h
100/100
100/150
100/200
100/200
100/200
–
–
H2O
EtOH
Toluene
a
Isolated yield
The bold entry is best reaction
conditions
Table 2 The effect of oxygen
source, pressure and temperature
on the reaction yield
Entry
Oxygen source
(pressure)
Time(h)
T(°C)
Yield (%)a
Amide
Acid
1
O2 (3 atm)
O2 (4 atm)
O2 (5 atm)
O2 (5 atm)
O2 (6 atm)
Air (5 atm)
H2O2
12
12
12
24
12
24
24
6
120
120
120
100
120
120
25
62
83
88
61
88
46
44
58
51
0
0
0
2
Reaction conditions:
3
0
benzonitrile (1.00 mmol),
CoCl2Á6H2O (1.00 mmol), Zn
(1.00 mmol), EDA (2.00 mmol)
4
0
5
0
a
6
0
Isolated yield
7b
8b
9b
10c
25
13
32
0
b
H2O2 (5 mL)
c
H2O2
120
120
120
Under argon atmosphere
(5 atm)
H2O2
12
24
The bold entry is best reaction
conditions
–
Results and discussion
The aerobic hydrolysis of nitriles was performed using CoCl2, Zn, and ethylene-
diamine (EDA) under solvent-free conditions at 120 °C. In order to optimize the
reaction conditions, the hydrolysis of benzonitrile as a model substrate was
investigated in the presence of various amounts of Co(II), Zn, and ethylenediamine
(EDA). At low amounts of Co(II), the reaction yield was low even over a long
duration time. As the catalyst amount was increased to 100 mol%, the reaction
carried out more efficiently (Table 1, entries 1–6). The amount of Zn optimized with
100 mol% of Zn as the best result (Table 1, entries 7–9). Introduction of EDA as a
123

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
S. Keshipour, A. Shaabani
Table 3 The effect of oxidation states of cobalt and zinc on the reaction
Entry
Promoting system (mmol)
Yield (%)a
1
2
3
4
5
6
CoCl2/Zn (1/1)
CoCl2/ZnCl2 (1/1)
Co/ZnCl2 (1/1)
Co/Zn (1/1)
Zn (1)
88
11
17
83
0
ZnCl2 (1)
0
Reaction conditions: benzonitrile (1.00 mmol), H2O (1.00 mmol for entries 3–6), EDA (2.00 mmol), O2
(5 atm), 120 °C, 12 h
a
Isolated yield
Fig. 1 UV–Vis spectrum of the reaction mixture for hydrolysis of benzonitrile after completion of the
reaction dissolved in H2O (A), benzamide in H2O (B), and CoCl2/EDA in H2O (C); (kmax = 481 nm)
complexation ligand in 200 mol% was improved the reaction yield (Table 1, entries
10–12). After screening a variety of solvents, it was found that the reaction was
performed in good yield under solvent-free conditions (Table 1, entries 13–15).
The influence of pressure and temperature on the reaction yield was studied in the
next step. By increasing the pressure up to 5 atm and the temperature up to 120 °C,
the hydrolysis yield was increased (Table 2, entries 1–5). Using other sources of
oxygen such as air (5 atm) and H2O2, not only was the desired yield not obtained
(Table 2, entries 6–9) but carboxylic acid was produced as a by-product when we
used H2O2 (25 % at 25 °C after 12 h and 13 % at 120 °C after 6 h), and its amount
was increased in long reaction durations (Table 2, entries 7–9). It is important to
note that the reaction did not occur in the absence of O2 (under argon atmosphere,
5 atm) at 120 °C (Table 2, entry 10).
123