Recyclable, highly efficient and low cost nano-MgO for amide synthesis under SFRC: A convenient and greener 'NOSE' approach

Article abstract of DOI:10.1016/j.apcata.2013.02.016

A clean synthesis of amide derivatives has successfully been accomplished utilizing reusable nano-MgO under 'SFRC' (solvent free reaction condition). The 'green-ness' of this protocol makes it a benign alternative for the large scale synthesis.

Full text of DOI:10.1016/j.apcata.2013.02.016

Applied Catalysis A: General 456 (2013) 118–125
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Applied Catalysis A: General
journal homepage: www.elsevier.com/locate/apcata
Recyclable, highly efficient and low cost nano-MgO for amide
synthesis under SFRC: A convenient and greener ‘NOSE’ approach
Vijay Kumar Dasa, Rashmi Rekha Devib,1, Ashim Jyoti Thakura,∗
a Department of Chemical Sciences, Tezpur University, Napaam 784028, India2
b Defence Research Laboratory, Post Bag No. 2, Tezpur 784001, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A clean synthesis of amide derivatives has successfully been accomplished utilizing reusable nano-MgO
under ‘SFRC’ (solvent free reaction condition). The ‘green-ness’ of this protocol makes it a benign alter-
native for the large scale synthesis.
Received 22 November 2012
Received in revised form 15 February 2013
Accepted 17 February 2013
Available online xxx
© 2013 Elsevier B.V. All rights reserved.
Keywords:
Nano-MgO
NOSE
SFRC
Amide
Green-ness
1. Introduction
of methylarenes using ammonia surrogates [13]. In the recent work
[14], amide synthesis was achieved by water-soluble Gold/DNA cat-
Recently, in the domain of catalysis, nano magnesium oxide
(MgO) has gained a respectable status as catalyst [1,2]. MgO has
a basic property which is exploited in the high-yield synthesis of
important molecules [3]. Its adsorptive properties [4] can be used in
toxic waste remediation [5]. It has a high activity against bacteria,
spores and viruses because of its large surface area [6].
The widespread importance of amide moiety as one of the
most versatile functionalities in chemistry and biology has been
acknowledged [7]. Several catalysts and reagents [8–10] have been
reported to effect the amidation reaction. The drawbacks inherited
with these reagents and catalysts are their instability, sensitivity to
moisture, harsh reaction condition, prolonged reaction time, mod-
est yield, toxic/corrosive by-products and costly waste streams.
More recently, hydroxyapatite-supported silver NPs have been
used for the synthesis of amides via selective hydration of nitriles
in water [10]. Kobayashi et al. reported gold or gold/iron NPs cat-
alyzed amide synthesis [11]. Mizuno and coworkers synthesized
amides by hydration of nitriles promoted by amorphous MgO using
reduced amounts of water [12]. Mizuno et al. also reported the syn-
thesis of amides by MgO promoted liquid-phase aerobic oxidation
alyst. However, main difficulties associated with these cited works
were very high reaction temperature, longer reaction time and
application of expensive catalysts. Therefore, the synthesis of amide
eliminating these drawbacks is still a demanding and challenging
work for the chemists. Our group recently reported the synthesis of
N-methylamide catalyzed by water tolerant zirconyl chloride under
MWI [15]. Reddy et al. have reported an acknowledgeable work
on nano-MgO catalyzed N-formylation of aryl/alkyl amines using
formic acid under MWI [16]. As a part of our ongoing research pro-
gram for the development of the ‘NOSE’ (Nanoparticles-catalyzed
Organic Synthesis Enhancement) [17] chemistry in our laboratory,
we herein report recyclable nano-MgO for the synthesis of amides 3
in good to excellent yields under SFRC by reacting carboxylic acids
1 with amines 2 (Scheme 1).
2. Experimental
2.1. General procedure for the synthesis of amides
In an oven dried round bottomed flask (50 mL) nano-MgO
(5.0 mol%) were added and then alky/aryl amines (5.0 mmol) and
aromatic/aliphatic acid (5.0 mmol) was added. After that it was
allowed to stir on a pre heated oil bath at 70 ◦C under aerobic condi-
tion till the required time (the progress of the reaction was judged
by TLC). After the completion, the reaction mixture was brought
to room temperature and ethyl acetate (3 × 10 mL) was added to
∗
Corresponding author.
E-mail address: ashim@tezu.ernet.in (A.J. Thakur).
Tel.: +91 3712 258508; fax: +91 3712 258534.
Tel.: +91 3712 275059; fax: +91 3712 267005/6.
1
2
0926-860X/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.apcata.2013.02.016

V.K. Das et al. / Applied Catalysis A: General 456 (2013) 118–125
119
O
O
SFRC, 70 0 C
R2
+
OH
R2 NH2
65-98 % yield
R1
N
H
5 mol% MgO
R1
3
1
2
R1 = H, alkyl, aryl
R2 = Alkyl, aryl
(i) Isolation by centrifugation (3,000 rpm)
(ii) Reused upto 5th cycle
Scheme 1. General representative scheme for the synthesis of amides.
O
H stretching and bending bonded with Mg and secondly, O
H
stretching and bending attached at the surface of the samples.
The O H stretching bonded with Mg appeared as a sharp peak
at 3703 cm−1, bending bond at 1443 cm−1. For the second, O
H
stretching appeared as a broad band at 3430 cm−1 while the bend-
ing at 1630 cm−1. These bands had been previously characterized
by several researchers [18,19].
The result from X-ray diffractogram (Fig. 3) presented the peaks
corresponding to (2 1 1), (2 2 0), (3 1 1), (4 1 1) and (3 3 1) planes that
gave a clear indication of the existence of cubic primitive MgO with
a lattice constant a, of 0.4839 nm and the peaks can be assigned to
the pure phase of MgO (JCPDS PDF # 76-1363).
Fig. 1. EDX analysis of pure nano-MgO.
The crystalline sizes were determined by using Scherrer equa-
tion by considering the two intense peaks (2 2 0) and (3 1 1) from
XRD pattern. The crystalline sizes were found to lie between 17.4
and 16.4 nm calculated from the X-ray line broadening by applying
full width half maximum (FWHM) of characteristic peaks (2 2 0)
and (3 1 1) to the Scherrer equation. The theoretical particle size
was also calculated from the surface area assuming particles to be
spherical in shape and the average particle diameter calculated was
18.12 nm (SBET = 92.458 m2 g−1 and ꢀ = 3.58 g cm−3). The total pore
it and then centrifuged at 3500 rpm to recover the nano catalyst.
Having done this, the reaction mixture was washed with water
and brine, dried over anhydrous Na2SO4, concentrated in a rotary
evaporator and finally the crude product was charged to column
chromatography (ethylacetate:hexane (3:7) as an eluent) for purifi-
cation and wherever necessary the products were recrystallized
from hot ethanol.
volume of MgO nanopowder is found to be 0.4313 mL g−1
.
3. Results and discussion
The surface morphology of nano-MgO was studied using scan-
ning electron microscope (Fig. 4(A) and (B)). It is evident from
Fig. 4(A) and (B) that the MgO NPs has an irregular shape and poor
microstructure resulting from agglomeration of MgO particles.
Particle size and external morphology of nano-MgO particles
were observed on a transmission electron microscope (Fig. 5).
Fig. 5(A) shows isolated particles with an average diameter of
45 2 nm as well as a network of connected particles. The particles
with an average diameter of 15 2 nm and 6 2 nm can be evident
3.1. Characterization of the catalyst
To characterize nano-MgO (procured from Sigma–Aldrich), at
first EDX analyses (Fig. 1) were performed to determine the ele-
mental constituents of it. It showed that weight% of Mg and O is
57.29 and 42.71 and atomic% is 50.12 and 50.88 respectively. Thus,
the EDX suggests the presence of only Mg and O in the nano-MgO
sample.
For the identification of functional groups, bonding information,
study of strength and fraction of hydrogen bonding, the FT-IR spec-
trum (Fig. 2) was recorded. It is revealed from Fig. 2 that there
are two types of OH bonding exist in these spectra. First, is the
Fig. 2. FTIR spectrum of nano-MgO.
Fig. 3. XRD pattern of MgO nanoparticles.

120
V.K. Das et al. / Applied Catalysis A: General 456 (2013) 118–125
Fig. 4. SEM micrographs of (A) MgO nanopowder at lower resolution and (B) MgO nanopowder at higher resolution.
Fig. 5. TEM images of nano-MgO at (A) 0.5 ␮m, (B) 50 nm and (C) 20 nm.
from Fig. 5(B) and (C). It can also be seen that some agglomera-
tion was present and this was attributed to the large surface area
of nano-MgO.
The TGA curve measures the compositional changes associated
with the calcinations processes and is shown in Fig. 6. The two step
pattern of weight loss has been indicated in Fig. 6 in the tempera-
ture range of around 110 ◦C and 345 ◦C.
2a (1 mmol, 0.09 mL) was considered. The reaction progress was
monitored initially at room temperature and then by heating on
preheated oil bath up to 120 ◦C. Under this condition the reac-
tion did not proceed and the starting materials remained intact
(Table 1, entry 1). Then we increased the temperature up to 150 ◦C
maintaining the same reaction condition but it also failed to yield
the product (Table 1, entry 2). Observing these negative results,
the importance of catalyst was realized. With this notion in mind,
we started the reaction with 10 mol% of nano-MgO at 120 ◦C that
provided 32% yield (Table 1, entry 3). Next, we carried out the
same reaction at 70 ◦C expecting a better outcome with shorter
rate. To our delight, a yield of 70% was obtained (Table 1, entry
4). For further improvement in the yield of amide and to under-
stand the role of nano-MgO, the model reaction was performed
at low catalyst loading. Significant increase in product formation
was observed using 5 mol% of nano-MgO which gave 96% yield in
10 min (Table 1, entry 6). Increasing the catalyst loading to more
than 5 mol% might have reduced the surface area due to the aggre-
gation of the particles which in turn decreased the yield of the
desired products. The results of catalyst loading (Table 1, entries
4–8) indicate that catalytic activity of nano-MgO increases from 1
to 3 mol%, attains the maximum activity at 5 mol% and after that
3.2. Optimization of the reaction condition
To optimize the reaction condition (Table 1), a model reaction
(Scheme 2) between benzoic acid 1a (1 mmol, 122 mg) and aniline
O
COOH
H2N
N
H
Catalyst
+
2a
Scheme 2. Model reaction.
3a
1a
Fig. 6. TGA curve of nano-MgO.

V.K. Das et al. / Applied Catalysis A: General 456 (2013) 118–125
121
Table 1
Catalyst screening and optimization.a
Entry
Catalyst
Solvent
Temp. (◦C)
Time (h)
Yield (%)b
TON
1
2
None
None
SFRC
SFRC
SFRC
SFRC
SFRC
SFRC
SFRC
SFRC
SFRC
SFRC
SFRC
SFRC
SFRC
CH3CN
H2O
120
150
120
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
70
9
9
2
1
NRc
NRc
32
70
74
96
64
30
5
12
5
Trace
Trace
35
30
>27
40
44
20
0
0
3d
4d
5e
Nano-MgOi
Nano-MgOi
Nano-MgOi
Nano-MgOi
Nano-MgOi
Nano-MgOi
Et3N
12.8
28
29.6
38.4
25.6
12
2
4.8
2
0
0
14
12
10.8
16
17.6
8
24
25.6
9.2
50 min
10 min
6f
7g
1.5
3
7
7
7
7
7
3
5
5
4
6
2
5
8
8
8h
9f
10f
11f
12f
13
14
15
16
17
18
19
20
21
22f
Imidazole
Pyridine
PPh3
K2CO3
Nano-MgOi
Nano-MgOi
Nano-MgOi
Nano-MgOi
Nano-MgOi
Nano-MgOi
Nano-MgOi
Nano-MgOi
Bulk-MgO
CH3OH
THF
Toluene
DMSO
Xylene
DMF
60
64
23
SFRC
a
Reaction condition: 2a (0.2 mL, 3 mmol), 1a (366 mg, 3 mmol), SFRC or solvent (5 mL).
b
c
d
e
f
Isolated yields.
No reaction.
10 mol% catalyst was used.
7 mol% catalyst was used.
5 mol% catalyst was used.
3 mol% catalyst was used.
1 mol% catalyst was used.
Particles size (17.4–16.4 nm).
g
h
i
it starts decreasing. Increasing the catalyst loading to more than
5 mol% might have reduced the surface area due to the aggregation
of the particles which in turn decreased the yield of the desired
products. It is important to note that when the model reaction was
performed at different mol% (other than 5 mol%) of nano-MgO by
keeping the scavenging time constant (10 min), poor yields (5–19%)
were obtained. As nano-MgO is basic in nature, therefore, we com-
pared the catalytic activity of nano-MgO with several base catalysts
(Table 1). It is evident from the Table 1 that nano-MgO showed the
best performance amongst all as some of the catalysts decomposed
at 70 ◦C (Table 1, entry 9). In some cases, catalyst isolation was
noticeably tedious (Table 1, entries 10 and 11) and a few of them
provided trace yield (Table 1, entry 12). We have also checked the
effect of solvent on the yield and the rate of the amide formation.
However, application of solvent could not dramatically enhance
both the rate and yield of amide at 70 ◦C using 5 mol% of nano-MgO
(Table 1, entries 14–21). When bulk MgO was introduced in the
model reaction for comparing its activity with the nano-MgO, it
was observed that bulk MgO could catalyze the reaction by giving
poor yield and longer reaction time (Table 1, entry 22). The crucial
breakthrough was observed under SFRC (Table 1, entry 6). The turn
over number (TON) was also calculated for each catalyst and the
graph is shown in Fig. 7. From the graph it is seen that the TON was
the highest under SFRC at 70 ◦C. These outcomes provoked us to
continue the reaction under SFRC using our ‘NOSE’ approach.
nano-MgO used in this study is in the range 9.8 < H < 15.0. The basic
strength and total basicity of various loading of nano-MgO is pre-
sented in Table 2. Nano-MgO has the stronger base strength and a
higher amount of basicity at 5 mol% loading (Table 2, entry 3) than
the mentioned ones (Table 2, entries 1–2 and 4–5).
As suggested by the results in Table 2, strong base sites are dif-
ficult to generate with low loading of nano-MgO (Table 2, entries
1 and 2). When the loading of nano-MgO was increased to 7 mol%
and 10 mol%, the base strength also got decreased which might be
attributed to the aggregation of particles reducing the active sites
and surface area. Hence, nano-MgO attained the maximum basicity
at 5 mol% loading for synthesizing amide in excellent yield (96%).
With this encouraging catalysis by nano-MgO in the amidation
reaction, we then extended our ‘NOSE’ approach to other nanocata-
lysts considering the same model reaction (Scheme 2) to investigate
the efficiency of the different nanocatalysts in the amide synthesis.
The results summarized in Table 3 evident that at 5 mol% catalyst
loading, only nano-MgO showed the best catalytic performance at
70 ◦C (Table 3, entry 7). But, the other mentioned nanocatalysts
3.3. Basicity measurement of nano-MgO
The basicity of nano-MgO was determined using Hammett indi-
cator and benzoic acid titration method [20,21]. The following
Hammett indicators with their base strength (H ) were used for the
basicity determination: Bromothymol Blue (H = 7.2), phenolphtha-
lein (H = 9.8), 2,4-dinitroaniline (H = 15.0) and 4-nitroaniline
(H = 18.4). With all these indicators except for 4-nitroaniline a
change in color was observed. Thus, the strength of basicity of
Fig. 7. TON of various catalysts from Table 1.

122
V.K. Das et al. / Applied Catalysis A: General 456 (2013) 118–125
Table 2
Basicity and yield of amide using different amount of loading of nano-MgO.
Entry
Catalyst loading (mol%)
Basicity (mmol/g)
7.2 < H < 9.8
Total basicity (mmol/g)
Yield (%)a
9.8 < H < 15.0
15.0 < H < 18.4
1
2
3
4
5
1
3
5
7
10
0.83
1.6
2.2
1.9
1.7
2.5
3.8
5.3
4.1
3.3
3.3
5.2
7.1
5.7
4.7
6.6
10.6
14.6
11.7
9.7
30
64
96
74
70
a
Isolated yield.
Table 3
Optimization of model reaction (Scheme 2) with nanocatalysts.a
Entry
Nanocatalysts (size)
Temp. (◦C)
Time (min)
Yield (%)b
1
2
3
4
5
6
7
8
␣-Fe2O3 (19 nm)
␥-Fe2O3 (8 nm)
Fe2O3 (12 nm)
Fe3O4 (<50 nm)
FeO(OH) (20–40 nm)
TiO2 (<80 nm)
70
70
70
70
70
70
70
70
180
100
90
60
80
300
10
60
44
35
40
55
36
Trace
96
MgO (17.4–16.4 nm)
Basic Al2O3 (37.4–39.7 nm)
15
a
5 mol% of catalyst was used.
Isolated yield.
b
provided comparatively poorer yield at 70 ◦C with longer reaction
time.
acid with aniline substituted with both electron donating and elec-
tron withdrawing groups and we obtained acetamide derivatives
in good to excellent yields (Table 4, entries 23–33). It is interest-
ing to note that when o-phenylenediamine was treated with acetic
acid, instead of amide bond formation, cyclization occurred afford-
ing 2-methylbenzimidazole in excellent yield (Table 4, entry 34).
Aliphatic amines also reacted with acetic acid to furnish the prod-
ucts in excellent yields (Table 4, entries 35 and 36). The reaction
of propanoic acid and butanoic acid with aryl amines also afforded
the expected products in elevated yields (Table 4, entries 37 and
38). The reaction of methylamine with propanoic acid, and aniline
with cyclohexanoic acid also proceeded efficiently giving the cor-
responding products in good yields (Table 4, entries 39 and 40). The
attempts of producing amides using cyanoacetic acid and trifluo-
roacetic acid failed under the current methodology. It might be due
to the fast decarboxylation under the reaction condition and rapidly
formed carboxylate salts of aniline decomposed kinetically before
condensation with amines. However, dicarboxylic acids (such as
adipic and malonic acid) and the long chain monocarboxylic acids
(such as lauric and behenic acid) remained unreactive with aniline
even after stirring at 80–100 ◦C for more than 24 h. The tolerability
of different electron withdrawing and electron donating groups in
the amines established the compatibility of those moieties toward
the reaction condition.
3.4. Synthesis of amide derivatives catalyzed by nano-MgO
Prompted by this convenient experimental reaction condition,
we next approached to assess the generality of various aromatic,
heterocyclic and aliphatic amines with carboxylic acids under
the standardized condition and the outcomes are summarized in
Table 4. It can be seen from Table 4 that nano-MgO exhibits out-
standing activity in the amide synthesis for both electron rich and
electron poor anilines and benzoic acids (Table 4, entries 1–15).
However, anilines substituted with electron withdrawing groups
gave slightly lower yields (Table 4, entries 4, 5 and 8–10) than
those substituted with electron donating moieties (Table 4, entries
11–15). Benzoic acid having electron donating groups produced
higher yield (Table 4, entry 3) than those with electron pulling
motifs (Table 4, entries 2, 6 and 7). Benzylamine also reacted
with several aromatic acids providing good to excellent yields
(Table 4, entries 16–18). Aliphatic amines under the present reac-
tion condition when treated with benzoic acid gave excellent yields
(Table 4, entries 19 and 20). 2,6-Dimethyl-4-nitro-phenylamine
having both electron pulling and pushing groups on the benzene
ring also provided high yield (Table 4, entry 21). Benzylamine
underwent reaction readily with phenylacetic acid producing good
yield (Table 4, entry 22). We also studied the reaction of acetic
In the plausible mechanism, it has been hypothesized that
nano-MgO activates the aryl/alkyl carboxylic acid on its surface
R1
OH
H
R1
O
H
R1
OH
R1
N
R2
H
H
H
C
O
R2
.
.
+
N
N
N
H
_
O
H
OH
O
R2
R2
2+
2+
Mg
2-
2-
2-
2+
Mg
2-
2+
Mg
2-
2+
Mg
2-
O
O
O
O
O
O
Mg
O
H
H
Scheme 3. Tentative mechanism for the synthesis of amides.

V.K. Das et al. / Applied Catalysis A: General 456 (2013) 118–125
123
Table 4
Nano-MgO catalyzed synthesis of amides 3.
Entry
R1
R2
Time (min)
Yield (%)a,b
Melting point (◦C)
1
2
3
4
5
6
7
8
C6H5
C6H5
C6H5
C6H5
3-ClC6H4
4-ClC6H4
C6H5
10
18
15
15
17
20
22
20
19
25
10
10
10
10
10
12
16
96
92
94
90
90
92
92
90
90
90
96
96
96
95
95
98
91
162.5–163.5
200.3–201.3
137.2–138.3
172.2–173.4
177.0–178.7
93.1–94.6
98.0–100.4
95.4–96.8
156.2–157.2
196.8–198.5
58.1–59.8
4-ClC6H4
2-OHC6H4
C6H5
C6H5
3-NO2C6H4
4-NO2C6H4
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
2-OCH3C6H4
3-OCH3C6H4
4-OCH3C6H4
2-CH3C6H4
4-CH3C6H4
C6H5CH2
C6H5CH2
9
10
11
12
13
14
15
16
17
104.1–105.3
155.3–156.3
144.5–145.5
156.5–157.2
C6H5
C6H5
4-OCH3C6H4
106.6–107.5
c
d
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34e,f
35
36
37
38
39
40
C6H5CH2
CH3
C6H11
2,6-(CH3)2-4-NO2C6H2
C6H5CH2
C6H5
2-ClC6H4
3-ClC6H4
2-NO2C6H4
3-NO2C6H4
4-NO2C6H4
4-OCH3C6H4
4-CH3C6H4
4-OHC6H4
4-COOHC6H4
C6H5CH2
2-NH2C6H4
CH3
27
10
30
22
33
10
20
17
20
30
33
15
15
10
35
25
30
60
80
90
88
98
92
90
90
98
96
92
90
90
88
97
97
93
91
95
94
98
96
89
90
92
90
C6H5
C6H5
C6H5
C6H5CH2
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
76.1–78.1
144.7–145.2
195.1–197.1
118.1–119.5
111.0–112.8
88.7–89.1
179.3–180.9
93.3–94.2
156.6–158.0
208.4–209.8
137.7–138.4
154.0–155.0
170.5–171.8
259.3–261.9
60.5–62.0
175.6–177.1
26.1–27.5
101.0–103.3
128.3–129.1
CH3
C6H11
C6H5CH2
C6H5
CH3
C6H5
CH3CH2
CH3 CH2CH2
CH3CH2
C6H11
120
85
30
93.6–94.8
d
148.2–149.5
a
Yields refer to the isolated pure products.
b
c
d
e
f
Products were characterized by IR and NMR (1H and 13C) spectroscopy, MS and also by comparing their melting points with the authentic ones.
Colorless oil.
Liquid compound.
2 equiv. of acetic acid was used.
2-Methylbenzimidazole was formed.
throughout the formation of amides (Scheme 3). A mechanism akin
to this has been reported previously [16].
It is demonstrated in the Table 5 that nano-MgO maintained its
catalytic activity up to the 5th cycle and after that yield of N-
phenylbenzamide went down markedly.
In the present work, we also conducted a comparative study
on FTIR spectra of fresh and reused nano-MgO (after 5th run). It is
found that there are shifts in the values of stretching frequencies
as depicted in Fig. 8(A) which may be the reason for lower yield
of N-phenylbenzamide (Scheme 4) after 5th run. Moreover, there
is an appearance of a new peak at 1121 cm−1 which might be due
to the presence of impurity after 5th run. The scanning electron
micrograph of recycled nano-MgO after 5th run (Fig. 8(B)) was also
recorded. The recovered nano-MgO after 5th cycle showed a clear
picture of highly agglomerated particles whose omnipresence in
the reaction system might play a key role in reducing the yield of
the product and in increasing time.
3.5. Recycling experiment of nano-MgO
The recyclability of a catalyst is a key point in the framework of
green chemistry. The recycling experiment for nano-MgO was car-
ried out by considering the model reaction under the standardized
condition (Scheme 2).
After the reaction, ethyl acetate was poured into the reaction
mixture and then ultra centrifuged (3500 rpm) to pellet out the
nano-MgO. The separated particles were washed with hot ethanol
(5 × 10 mL) to remove all the organic impurities. Finally, it was
decanted and dried in an oven at 100 ◦C for 7 h. Then the catalyst
was reused in the next run in the reaction as shown in Scheme 4.
The TEM image of reused nano-MgO after 5th run (Fig. 9(A))
manifested the rupture in the network of connected particles which
might have taken part in the marginal loss of its activity. The net-
work structure of nano-MgO may have tailored its high catalytic
activity. The XRD pattern of fresh nano-MgO was also compared
with reused one (after 5th run) and is shown in Fig. 9(B). It showed
some important changes. Thus, it is evident (Fig. 9(B)) that the
COOH
Nano-MgO
NH2
H
N
+
700C,SFRC
O
Scheme 4. Measurement of green metrics.

124
V.K. Das et al. / Applied Catalysis A: General 456 (2013) 118–125
Table 5
Reusability of nano-MgO on the yield of N-phenylbenzamide.
No. of cyclesa
Fresh
1st run
2nd run
3rd run
4th run
5th run
6th run
7th run
Yield (%)b
Time (min)
TON
96
10
38.4
96
10
38.4
96
10
38.4
96
10
38.4
96
10
38.4
96
10
38.4
88
30
35.2
80
60
32
a
Reaction condition: 5 mmol aniline, 5 mmol benzoic acid, 0.25 mmol (5 mol%) nano basic MgO, 70 ◦C.
Yields refer to the isolated pure N-phenylbenzamide.
b
Fig. 8. (A) Comparison of FTIR spectrum of fresh nano-MgO with recycled one after 5th run, (B) SEM micrograph of reused nano-MgO after 5th run.
Fig. 9. (A) TEM image of reused nano-MgO after 5th run, (B) comparison of XRD pattern of fresh nano-MgO with the reused one after 5th run.
sintensity of the highest peak (2 2 0) in fresh nano-MgO is decreased
completely in the recycled one. Apart from this, the intensities of
the peaks (3 1 1), (4 1 1) and (3 3 1) also diminished in the reused
nano-MgO. It may be due to either the leaching of Mg2+ from MgO or
blockage of the active pores which in turn perhaps reduced the yield
of N-phenylbenzamide after 5th run (Scheme 4). Moreover, there is
an appearance of a new peak at about 62◦ which might be referred
to the impurity stuck into the catalyst during the consecutive cycles.
3.6. Leaching study of nano-MgO
To verify the amount of Mg2+ lost from nano-MgO during its
recycling (after 5th cycle) which caused decrease in the yield of
amidation product, the leaching study was performed on a UV visi-
ble spectrophotometer (Fig. 10). The reused nano-MgO experienced
34.7% Mg2+ leaching from its surface which might have reduced its
catalytic activity after 5th run (Scheme 4).
Table 6
A comparison of “green-ness” among the catalysts/reagents in the synthesis of N-benzylbenzamide (Scheme 4).
Catalysts/reagents
E-factora
Mass intensity
Atom economy (%)
Yield (%)b
IBAc
251.7
31.8
22.6
17
397.3
32.9
67
92.13
53.9
48.5
50 [22]
92 [23]
82 [24]
72 [25]
CDId
DCC
SOCl2
25
85.3
Sulfated tungstate
Nano-MgO
9.3
1.07
26.3
1.09
92.13
92.13
81 [26]
98 (our work)
a
E-factor shown does not account for the waste produced in the synthesis of reagents/catalysts.
Yield refers to the isolated pure N-benzylbenzamide.
ortho-N,N-diisopropylbenzylaminoboronic acid catalyst.
N,N-carbonyldiimidazole.
b
c
d

V.K. Das et al. / Applied Catalysis A: General 456 (2013) 118–125
125
Acknowledgment
VKD thanks UGC for Rajiv Gandhi National Fellowship to him.
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.apcata.
2013.02.016.
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3.7. Measurement of “green-ness” by using green metrics
The “green-ness” of the present methodology was evaluated by
making use of different parameters of green chemistry (Table 6),
that shows the superiority of nano-MgO over other catalysts.
The waste produced during the course of the reaction is
the least in our protocol compared to the other methodologies
[22–26]. Moreover, the issues like solvent reusability and catalyst
recyclability are omitted by E-factor which absolutely raises the
accuracy.
4. Conclusions
In conclusion, we have developed a practical and greener
‘NOSE’ protocol for the clean synthesis of both aliphatic and aro-
matic amides utilizing nano-MgO as an efficient, reusable and
cheap catalyst under SFRC. Simple experimental condition, varied
substrate compatibility, high yields of the products, chemo selec-
tivity, and non-hygroscopic nature of catalyst make our protocol a
more potent benign alternative over conventional ones for amide
synthesis.