A mild and expeditious synthesis of amides from aldehydes using bio glycerol-based carbon as a recyclable catalyst

Article abstract of DOI:10.1016/j.tetlet.2012.03.051

The new bioglycerol-based carbon catalyst acts as an efficient, readily available, and reusable catalyst for the synthesis of amides, when aldehyde and hydroxylamine hydrochloride react in acetonitrile.

Full text of DOI:10.1016/j.tetlet.2012.03.051

Tetrahedron Letters 53 (2012) 2636–2638
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Tetrahedron Letters
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A mild and expeditious synthesis of amides from aldehydes using bio
glycerol-based carbon as a recyclable catalyst
K. Ramesh a, S. Narayana Murthy a, K. Karnakar a, K. Harsha Vardhan Reddy a, Y. V. D. Nageswar a,
,
⇑
M. Vijay b, B. L. A. Prabhavathi Devi b, R. B. N. Prasad b
a Natural Product Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 607, India
b Centre for Lipid Research, Indian Institute of Chemical Technology, Hyderabad 500 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The new bioglycerol-based carbon catalyst acts as an efficient, readily available, and reusable catalyst for
the synthesis of amides, when aldehyde and hydroxylamine hydrochloride react in acetonitrile.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 10 February 2012
Revised 12 March 2012
Accepted 15 March 2012
Available online 23 March 2012
Keywords:
Aldehydes
Hydroxylamine hydrochloride
Amides
Acetonitrile
Catalyst
Benzamides represent an important class of organic compounds
in pharmaceutical chemistry with potential biological activity,1
playing a crucial role in the context of heterocyclic chemistry.
These are important intermediates in organic synthesis,2 as well
as in plastics, lubricants, detergent manufacturing, and in pharma
applications.3 Oxyclozanide (Fig. 1) was developed as an anti hel-
mintic agent effective against Fasciola hepatica in the treatment
of liver fluke infection.4 Recently Narasimhan et al. reported the
development of useful QSAR (quantitative structure–activity rela-
tionship) models for antimicrobial activity,5 and anti-inflammatory
activity.6 Numerous methods have been reported for the synthesis
of substituted benzamides involving catalysts like Ir,7 Rh,8 Ru,9 Ag/
Au,10 Pd11 compounds, anhydrous oxalic acid,12 chloral,13 sulfamic
acid,14 cyanuric chloride/DMF,15 ethyl chloroformate/boron tri-
fluoride etherate16, and chlorosulfonic acid.17 However, the above
mentioned methods suffer from one or more disadvantages such
as the use of hazardous organic solvents, expensive moisture-sen-
sitive catalysts, tedious work-up conditions, longer reaction times,
or large volume of catalyst loadings. In continuation of our efforts
toward the development of novel environ friendly methodolo-
gies,18 herein, we report a mild and efficient one-pot protocol for
the synthesis of substituted benzamide derivatives for the first
time by a two-component reaction involving aldehydes, and
bioglycerol-based carbon catalyst in acetonitrile (Scheme 1). In re-
cent years carbon-based solid acid catalysts19 have gained promi-
nence due to their significant advantages over homogeneous
liquid phase mineral acids such as increased activity, selectivity,
longer catalyst life, negligible equipment corrosion, ease of product
separation, and reusability. These carbon based catalysts were
obtained by incomplete carbonization of sulfo-aromatic polycyclic
carbon catalyst from bioglycerol (biodiesel by-product) and also
from glycerol-pitch (waste from fat splitting industry) by in situ
partial carbonization and sulfonation in a single pot.20 These car-
bon catalysts were demonstrated for their effectiveness for the
esterification, THP protection and deprotection of alcohols and
phenols, respectively. In continuation of exploring the possible
applications for the carbon-based solid acid catalyst,21 herein we
report a facile and efficient one-pot synthesis of substituted benz-
amides for the first time (Scheme 1), catalyzed by bioglycerol de-
rived carbon acid catalyst.
Benzaldehyde and hydroxylamine hydrochloride were used as
model substrates to optimize the reaction conditions. Effect of
parameters such as bases, solvents, and reaction temperature were
studied (Table 2). Several bases namely Cs2CO3, KOH, K2CO3, and
Na2CO3 were employed in the reaction. Of these screened bases,
Cs2CO3 was found to be an excellent base (Table 2, entry 7) to carry
forward the reaction in terms of rate of the reaction, and product
yield and the corresponding results were shown in Table 2. Later
the efficacy of different solvents was investigated toward the
optimization. While evaluating the influence of different solvent
hydroxylamine hydrochloride using
a novel and recyclable
⇑
Corresponding author. Tel.: +91 40 27191654; fax: +91 40 27160512.
E-mail address: dryvdnageswar@gmail.com (Y. V. D. Nageswar).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.03.051

K. Ramesh et al. / Tetrahedron Letters 53 (2012) 2636–2638
2637
Table 1 (continued)
Cl
Entry
Aldehyde
Product
Yieldb (%)
Cl
CHO
O
H
N
Cl
Cl
NH2
10
74
75
77
Br
O
OH
Br
OH
Cl
CHO
O
11
12
NH2
Figure 1. Oxyclozanide.
CHO
O
NH2
NC
O
NH2
NC
CHO
CHO
O
Catalyst, Cs2CO3
CH3CN, 60-65 °C
MeO
NH2-OH.HCl
+
NH2
13
14
74
71
OMe
O
R
R
CHO
OH
R = -H, -Cl, -Br, -NO2, -F, -CH3, -OCH3, -CN, -OC2H5, -Ph, -o-allyloxy.
NH2
Scheme 1. Synthesis of substituted benzamides.
OCH3
OH
OCH3
S
NH2
CHO
15
16
73
74
S
Table 1
Synthesis of substituted benzamidesa
O
CHO
O
Entry
Aldehyde
CHO
Product
Yieldb (%)
75
NH2
O
EtO
EtO
1
NH2
NH2
CHO
O
CHO
CHO
O
NH2
17
18
73
71
O
O
2
3
4
73
74
75
CHO
O
NH2
CHO
O
NH2
MeO
OMe
MeO
OMe
OMe
O
NH2
OMe
a
Reaction conditions: aldehydes (1.0 mmol), NH2OHÁHCl (1.0 mmol), Cs2CO3
(1.0 mmol), catalyst (10 wt %), CH3CN (10 mL).
b
Isolated yield.
CHO
O
NH2
5
6
7
78
76
75
O2N
Table 2
O2N
Optimization conditions for the synthesis of substituted benzamidesa
CHO
O
Entry
Base
Solvent
T (°C)
Yieldb (%)
NH2
O
1
2
3
4
5
6
7
KOH
CH3CN
Toluene
Ethanol
Methanol
DMSO
60–65
70–75
60–65
50–55
80–85
rt
46
42
40
28
44
44
75
NO2
K2CO3
Na2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
NO2
CHO
CHO
CH3CN
CH3CN
NH2
NH2
Cl
60–65
Cl
a
Reaction conditions: aldehydes (1.0 mmol), NH2OHÁHCl (1.0 mmol), base
O
(1.0 mmol), catalyst (10 wt %), solvent (10 mL).
b
Isolated yield.
HO
8
9
72
73
OH
HO
OH
systems for bioglycerol-based carbon catalyzed synthesis of substi-
tuted benzamides, such as toluene, ethanol, methanol, DMSO, and
CH3CN (Table 2, entries 2–5 and 7), CH3CN was observed to be the
promising solvent, attaining optimum yields (Table 2, entry 7). In
all these reactions bio glycerol-based carbon catalyst can be recov-
ered and reused. After the reaction, the reaction mass was cooled
CHO
O
NH2

2638
K. Ramesh et al. / Tetrahedron Letters 53 (2012) 2636–2638
6. Gangwal, N. A.; Narasimhan, B.; Mourya, V. K.; Dhake, A. S. Indian J. Heterocycl.
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Recyclability of the catalyst
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8. (a) Park, S.; Choi, Y.; Han, H.; Yang, S. H.; Chang, S. Chem. Commun. 1936, 2003;
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Mizuno, N. Chem. Asian J. 2008, 3, 1715; (d) Kim, M.; Lee, J.; Lee, H.-Y.; Chang, S.
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Cycles
Yield (%)
Catalyst recovered (%)
Fresh
75
73
72
71
88
86
85
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1
2
3
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to room temperature and catalyst was filtered and washed with
ice-cold methanol and dried. The recovered catalyst was further
used in the reaction with the same substrates and checked for
the yields and catalytic activity of the recovered catalyst, as shown
in Table 3. It was observed that the yields of highly substituted
benzamides diminished slightly after two to three recycles. The
experimental results are included in Table 1. All the products were
characterized22,23 by 1H, 13C NMR, and mass spectra.
11. Ali, M. A.; Punniyamurthy, T. Adv. Synth. Catal. 2010, 352, 288.
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Reddy, V. P.; Rao, K. R.; Nageswar, Y. V. D. Tetrahedron Lett. 2009, 50, 6025; (d)
Murthy, S. N.; Madhav, B.; Reddy, V. P.; Nageswar, Y. V. D. Tetrahedron Lett.
2010, 51, 3649; (e) Shankar, J.; Karnakar, K.; Srinivas, B.; Nageswar, Y. V. D.
Tetrahedron Lett. 2010, 51, 3938; (f) Murthy, S. N.; Madhav, B.; Nageswar, Y. V.
D. Tetrahedron Lett. 2010, 51, 5252; (g) Ramesh, K.; Murthy, S. N.; Nageswar, Y.
V. D. Tetrahedron Lett. 2011, 52, 2362; (h) Ramesh, K.; Murthy, S. N.; Karnakar,
K.; Nageswar, Y. V. D. Tetrahedron Lett. 2011, 52, 3937; (i) Ramesh, K.; Murthy,
S. N.; Karnakar, K.; Nageswar, Y. V. D. Tetrahedron Lett. 2011, 52, 4734; (j) Anil
Kumar, B. S. P.; Madhav, B.; Harsha Vardhan Reddy, K.; Nageswar, Y. V. D.
Tetrahedron Lett. 2011, 52, 2862.
Conclusion
In summary, we have developed a simple, efficient, and eco-
friendly protocol for the synthesis of amides from aldehydes. This
simple and facile method will be an useful addition to green chem-
istry with an advantage that the reaction excludes moisture sensi-
tive or hazardous catalysts and elevated reaction temperatures,
and utilizes bioglycerol based carbon solid acid heterogeneous
recyclable catalyst.
19. (a) Hara, M.; Yoshida, T.; Takagaki, A.; Takata, T.; Kondo, J. N.; Hayashi, S.;
Domen, K. Angew. Chem. 2004, 116, 3015; (b) Toda, M.; Takagaki, A.; Okamura,
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Acknowledgements
We thank the CSIR, New Delhi, India, for fellowships to S.N.M.,
K.K., K.H.V.R, and UGC for fellowship to K.R.
20. Prabhavathi Devi, B. L. A.; Gangadhar, K. N.; Sai Prasad, P. S.; Jagannadh, B.;
Prasad, R. B. N. ChemSusChem. 2009, 2, 617.
21. Ramesh, K.; Murthy, S. N.; Karnakar, K.; Nageswar, Y. V. D.; Vijayalakhshmi, K.;
Prabhavathi Devi, B. L. A.; Prasad, R. B. N. Tetrahedron Lett. 2012, 44, 1126.
22. General experimental procedure for the synthesis of substituted benzamide
derivatives: To a stirred solution of acetonitrile (10 mL), aldehyde (1.0 mmol)
and bioglycerol-based carbon catalyst (10 wt %) were added and stirred for
10 min. To this NH2OHÁHCl (1.0 mmol) followed by Cs2CO3 (1.0 mmol) were
added, after which the reaction mixture was heated at 60–65 °C until
completion of the reaction as indicated by TLC. The reaction mixture was
cooled to room temperature and catalyst was filtered, the solvent was removed
by rotary evaporator. The crude residue was extracted with ethyl acetate
(3 Â 10 mL). The combined organic layers were extracted with water, saturated
brine solution, and dried over anhydrous Na2SO4. The organic layers were
evaporated under reduced pressure and the resulting crude product was
purified by column chromatography using ethyl acetate and hexane (2:8) as
eluents to give the corresponding substituted benzamide derivative in (71–
78%) yield. The identity and purity of the product were confirmed by 1H, 13C
NMR, and mass spectra.
23. Data for the representative examples of synthesized compounds benzamide (Table
1, entry 1); 1H NMR (300 MHz, CDCl3 + DMSO, TMS) d = 7.78 (d, 2H, J = 6.7 Hz),
7.53–7.40 (m, 4H), 7.25 (s, 1H); 13C NMR (75 MHz, DMSO,TMS) d = 168.38,
132.90, 130.40, 127.20, 126.62; EI-MS (m/z): 121 (M)+. 4-Methylbenzamide
(Table 1, entry 11); 1H NMR (300 MHz, CDCl3 + DMSO, TMS) d = 7.43 (d, 2H,
J = 8.1 Hz), 7.15 (d, 4H, J = 7.9 Hz), 2.37 (s, 3H, –CH3); 13C NMR (75 MHz,
DMSO,TMS) d = 150.20, 140.21, 131.01, 129.44, 126.95, 29.67; EI-MS (m/z): 135
(M)+.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.03.
051.
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