Silica-sulfuric acid: Novel, simple, efficient and reusable catalyst for hydration of nitrile to amide

Article abstract of DOI:10.14233/ajchem.2016.19907

Silica-sulfuric acid efficiently catalyzes conversion of aliphatic, substituted aromatic and hetero aromatic nitriles to their corresponding amides in good to excellent yields under reflux condition. Products obtained were purified by column chromatography method and characterized by ¹H NMR, ¹³C NMR and mass spectral analysis.

Full text of DOI:10.14233/ajchem.2016.19907

Asian Journal of Chemistry; Vol. 28, No. 10 (2016), 2177-2180
A
SIAN
J
OURNAL OF HEMISTRY
C
http://dx.doi.org/10.14233/ajchem.2016.19907
Silica-SulfuricAcid: Novel, Simple, Efficient and Reusable Catalyst for Hydration of Nitrile toAmide
1
2,*
3
2
SANDEEP CHANDRASHEKHARAPPA , KATHARIGATTA N. VENUGOPALA , RASHMI VENUGOPALA and BHARTI ODHAV
1Institute for Stem Cell Biology and Regenerative Medicine, NCBS, TIFR, GKVK, Bellary Road, Bangalore-560 065, India
2Department of Biotechnology and Food Technology, Durban University of Technology, Durban 4001, South Africa
3Department of Public Health Medicine, University of KwaZulu-Natal, Howard College Campus, Durban 4001, South Africa
*Corresponding author: E-mail: katharigattav@dut.ac.za; venugopalakn@gmail.com
Received: 11 February 2016;
Accepted: 25 May 2016;
Published online: 30 June 2016;
AJC-17963
Silica-sulfuric acid efficiently catalyzes conversion of aliphatic, substituted aromatic and hetero aromatic nitriles to their corresponding
amides in good to excellent yields under reflux condition. Products obtained were purified by column chromatography method and
characterized by 1H NMR, 13C NMR and mass spectral analysis.
Keywords: Silica-sulfuric acid, Nitriles, Amides, Hydration.
reaction temperatures (175 °C) [38]. Moreover, the tolerance
of base-sensitive functional groups such as carboxylic esters
has not been documented in these reports [15,35-38,51]. Such
chemo-selectivity is important in modern organic synthesis
[52,53], but is generally considered elusive in nitrile hydration
promoted by metal-loaded heterogeneous catalysts, a single
exception (Au/TiO2) [44] notwithstanding.A number of catalysts
have been developed for the synthesis of amide from nitrile
such as hydrogen peroxide/DMSO [9,54], hydrogen peroxide/
PTC [55], Na/FAP [56] and synthetic fluorapatites (FAP) [57].
Amide can also be prepared by metal complex such as palladium
[18], rhodium [58], sodium perborate [59], ruthenium complex
[60], chloromethylsilane [6] and ZnCl2 under microwave
condition [61]. On the other hand, heterogeneous process
enhances the selectivity in this reaction. Heterogeneous catalysts
such as a KF/Al2O3 [62], resins [63], KF/natural phosphate
[64] are used for conversion of nitrile to amide.
According to the reported literature, the conversion of
nitriles to amides requires an expensive catalyst and long
duration time. Moreover, some of the metal catalysts are not
easily available and some of the metal catalysts are to be used
with high precautions during the reaction conditions. Keeping
these reasons in mind, we developed a simple method for
conversion of nitrile to amides without affecting any substi-
tutions with in the molecule. However, the reported methods
suffer from drawbacks such as being expensive, explosive,
unavailable, low yield and polluting to environment to some
extent. Furthermore, some of these methods yield acid as a
side product. Therefore, a need still exists for versatile, simple
and environmentally friendly process for conversion of nitrile
INTRODUCTION
The hydration of nitriles into the corresponding amides
is very important in organic chemistry as well as in the chemical
industry. There are a number of different methods for this
conversion. Nitrile hydration is a classic transformation but
one which is still difficult to achieve, even with the range of
available reagents. Traditionally, various acids or bases were
used as catalysts [1-9]. Transition metal catalyzed methods
have been developed using Co [10,11], Mo [12], Ru [13-16],
Rh [17,18], Pd [19,20], Ir [21] and Pt [22-24]. Homogeneous
metal catalysis is frequently used in an industrial setting.
Intimate catalyst substrate interaction, mild reaction conditions
and an understanding of the catalytic process are recognized
as main advantages. The catalytic hydration of nitriles (RCN)
to carboxamides (RCONH2) represents a fundamentally impor-
tant pathway to these products in both laboratory and industrial
contexts [25-34]. Since the discovery of alumina-supported
ruthenium hydroxide catalysts [Ru(OH)x/Al2O3] byYamaguchi
et al. [15] solid-supported ruthenium has become an important
class of catalyst for nitrile hydration, demonstrating high
selectivity for carboxamide formation as well as other practical
advantages [35-50]. Although RuCl3·nH2O itself catalyzes
nitrile hydration, the choice of solid support is critically impor-
tant for achieving sufficient reactivity as well as for retaining
Ru species on support [15,37]. Examples of supports successfully
used for Ru species include inorganic Al2O3 [15], nanoferrite
[35] and magnetic silica [36]as well as organic chitosan [51],
amberlite [37] and Nafion [38]. However, these systems typically
require the use of microwave irradiation [35-37,51] or high

2178 Chandrashekharappa et al.
Asian J. Chem.
to amide. In this research we report silica-sulfuric acid as a
simple, efficient and reusable catalyst for the transformation
of amides from nitriles.
2H): 13C NMR (400 MHz, CDCl3): δ = 115, 123, 128, 150,
169; LC-MS: m/z = 136 (M+); Anal. calculated for C7H8N2O;
C, 61.75; H, 5.92; N, 20.58; Found: C, 61.74; H, 5.90; N,
20.59.
EXPERIMENTAL
2-Amino-5-chlorobenzamide (2h): 1H NMR (400 MHz,
CDCl3): δ = 6.6 (s, 2H), 7.15 (d, 2H), 7.6 (s, 1H), 7.80 (s, 1H);
13C NMR (400 MHz, CDCl3): δ = 114, 117, 118, 128, 132, 149,
170; LC-MS: m/z = 170 (M+);Anal. calculated for C7H7N2OCl;
C, 49.28; H, 4.14; N, 16.42; Found: C, 49.29; H, 4.15; N,
16.41.
1H NMR and 13C NMR spectrum were recorded on 400
MHz Bruker spectrometer using CDCl3 solvent. Molecular
weight of the synthesized compounds were checked using
LC-MS Agilent 1100 series with MSD Ion trap using 0.1 %
aqueous trifluoroacetic acid in acetonitrile system on C18-
BDS column for a 10 min duration and GC-MS. Commercially
available chemicals were procured from Sigma-Aldrich and
Alfa-Aesar and used without further purification.
General procedure for the preparation of amide from
nitrile: In a round bottom flask, aliphatic/substituted aromatic/
hetero aromatic nitrile (1 mmol), silica-sulfuric acid (1 mmol)
and toluene (10 mL) were taken under nitrogen atmosphere
and refluxed for 1-3 h. Completion of the reaction was moni-
tored on thin layer chromatography, LC-MS and GC-MS.
After reaction completion, the product obtained was filtered
and washed with ethyl acetate. Crude product was purified by
column chromatography using 60-120 mesh silica gel with n-
hexane-ethyl acetate solvent and recrystallized with appropriate
solvents. All the purified compounds were characterized by
1H NMR, 13C NMR, LC-MS/GC-MS and elemental analysis.
Acrylamide (2a): 1H NMR (400 MHz, CDCl3): δ = 5.5 (d,
1H), 6 (m, 2H), 7.1 (s, 1H), 8.0 (s, 1 H).13C NMR (400 MHz,
CDCl3): δ = 126, 132, 167; GC-MS: m/z = 71 (M+); Anal.
calculated for C3H5NO; C, 50.69; H, 7.09; N, 19.71; Found:
C, 50.70; H, 6.98; N, 19.72.
tert-Butyl 2-(4-carbamoylphenyl)acetate (2i): 1H NMR
(400 MHz, CDCl3): δ = 1.35 (s, 9H), 3.59 (s, 2H), 7.25 (d,
2H), 7.8 (d, 2H), 9.4 (s, 1H), 9.8 (s, 1H); 13C NMR (400 MHz,
CDCl3): δ = 9, 12, 29, 73, 127, 130, 138, 173; LC-MS: m/z =
235 (M+); Anal. calculated for C13H17NO3; C, 66.36; H, 7.28;
N, 5.95; Found: C, 66.33; H, 7.27; N, 5.98.
1
Methyl 2-(4-carbamoylphenyl)acetate (2j): H NMR
(400 MHz, CDCl3): δ = 3.51 (s, 2H), 3.7 (s, 3H), 6 (2H, br),
7.24 (d, 2H). 7.83 (d, 2H); 13C NMR (400 MHz, CDCl3): δ =
38, 48, 51, 127, 130, 134, 142, 173; LC-MS: m/z = 193 (M+);
Anal. calculated for C10H11NO3; C, 62.17; H, 5.74; N, 7.25;
Found: C, 62.23; H, 5.71; N, 7.28.
2-Aminopyridine 6-carbaxalmide (2k): 1H NMR (400
MHz, CDCl3): δ = 4 (2H br), 6.3 (2H), 7.1 (d, 1H), 7.7 (d,
1H), 7.9 (s, 1H); 13C NMR (400 MHz, CDCl3): δ = 112, 140,
149, 159, 169; LC-MS: m/z = 137 (M+); Anal. calculated for
C6H7N3O; C, 52.55; H, 5.14; N, 30.64; Found: C, 52.51; H,
5.19; N, 30.62.
RESULTS AND DISCUSSION
2-Hydroxyacetamide (2b):1H NMR (400 MHz, CDCl3):
δ = 3.7 (d, 2H), 5.3 (t, 2H), 7.2 (s, 2H); 13C NMR (400 MHz,
CDCl3): δ = 34, 116, 194 GC-MS: m/z = 75 (M+);Anal. calcu-
lated for C2H5NO2; C, 32.00; H, 6.71; N, 18.66; Found: C,
31.58; H, 6.68; N, 18.63.
In continuation of our effort for the development of
synthetic methods in organic synthesis [65,66] and pharma-
cologically active heterocyclic compounds [67-69], herewith
we have focused our attention on the preparation of amides
from nitriles catalyzed by silica-sulfuric acid (Scheme-I) in good
to excellent yields as shown in Table-1.
Benzamide (2c): 1H NMR (400 MHz, CDCl3): δ = 7.4 (m,
2H), 7.5 (m, 1H), 7.8 (m, 2H), 9.49 (s, 1H), 9.89 (s, 1H); 13C
NMR (400 MHz, CDCl3): δ = 127, 128, 132, 133, 169; LC-
MS: m/z = 121 (M+); Anal. calculated for C7H7NO; C, 69.41;
H, 5.82; N, 11.56; Found: C, 69.38; H, 5.83; N, 11.55.
3-Amino-4-methoxybenzamide (2d): 1H NMR (400 MHz,
CDCl3): δ = 3.7 (s, 3H), 4.7 (s, 2H), 6.78 (d, 1H), 7.0 (d, 1H),
7.1 (s, 1H), 7.16 (s, 1H), 7.6 (s, 1H);13C NMR (400 MHz,
CDCl3): δ = 55, 109, 113, 116, 127, 137, 149, 168; LC-MS:
m/z = 166 (M+); Anal. calculated for C8H10N2O2; C, 57.82; H,
6.07; N, 16.86; Found: C, 57.79; H, 6.04; N, 16.87.
O
Silica sulfuric acid
R
R
CN
NH2
R = aliphatic, substituted aromatic and hetero aromatic
Scheme-I: Hydration of nitrile group to amide group
To demonstrate the protocol, we selected benzonitrile and
substituted benzonitrile as model substrates, which smoothly
converted to benzamide in excellent yield (Table-1, entry-3)
and the same reaction was extended to substituted benzonitrile
also (entry 4-8 and 10). Interestingly, we observed that tert-
butyl group was unaffected under this reaction condition
(entry-9). Heterocyclic nitrile such as a pyridine moiety smoothly
converted to amide in excellent yield (entry-11). We also
observed that an aliphatic nitrile such as acrylonitrile yields
acrylamide (entry1) in excellent yield without affecting the
double bond which was not possible in DMSO condition. This
was an added advantage of this method and that 2-hydroxy
acetonitrile also underwent this conversion in excellent yield
(entry 2). Silica-sulfuric acid catalyst can also be used up to
three times without losing its catalytic activity.
1
2,6-Dichlorobenzamide (2e): H NMR (400 MHz,
CDCl3): δ = 7.33 (d, 2H), 7.4 (t, 1H) 13C NMR (400 MHz
CDCl3): δ = 127, 134, 135, 136, 169; LC-MS: m/z = 190 (M+);
Anal. calculated for C7H5NOCl2; C, 44.25; H, 2.65; N, 7.37;
Found; C, 44.21; H, 2.64; N, 7.37.
3-Aminobenzamide (2f): 1H NMR (400 MHz, CDCl3):
δ = 5.1 (s, 2H), 6.7 (s, 1H), 6.98 (dd, 1H), 7.0 (d, 2H), 7.1 (s,
1H), 7.70 (s, 1H); 13C NMR (400 MHz, CDCl3): δ = 113, 115,
118, 129, 135, 149, LC-MS: m/z = 136 (M+); Anal. calculated
for C7H8N2O; C, 61.75; H, 5.92; N, 20.58; Found: C, 61.76;
H, 5.91; N, 20.56.
4-Aminobenzamide (2g): 1H NMR (400 MHz, CDCl3):
δ = 5.5 (s, 2H), 6.5 (dd, 2H), 6.8 (s, 1H), 7.50 (s, 1H), 7.6 (dd,

Vol. 28, No. 10 (2016)
Silica-Sulfuric Acid: Novel, Simple, Efficient and Reusable Catalyst for Hydration of Nitrile to Amide 2179
TABLE-1
Conclusion
Silica-sulfuric acid efficiently catalyzes conversion of
PHYSICAL CONSTANTS OF CONVERSION
OF NITRILE TO AMIDE (1-11)
aliphatic, substituted aromatic and hetero aromatic nitriles to
their corresponding amides in good to excellent yields under
reflux condition without affecting any other substituent in
the molecule. It is also made observation on new method of
synthesis. The reactions performed are ecofriendly and the
used catalysts are easily available with low cost.
Reaction
Yield
(%)b
Nitrile
Product
time (h)a
1
2
2a
2b
2
88
79
CN
2.5
HO
CN
CN
3
2c
3
3
90
ACKNOWLEDGEMENTS
The authors are thankful to Institute for Stem Cell Biology
and Regenerative Medicine, National Research Foundation
(96807), South Africa and Durban University of Technology
for support and facilities.
CN
4
2d
83
NH2
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