Nano-MgO: An efficient catalyst for the synthesis of formamides from amines and formic acid under MWI

Article abstract of DOI:10.1007/s10562-010-0372-6

Nano-MgO a basic catalyst was prepared by solution combustion technique. It was characterized by powder XRD, SEM, BET and TEM analyses. It was used as a catalyst for the study of microwave-assisted N-formylation of various aromatic and alkyl amines with formic acid under solvent-free conditions. Nano-MgO showed excellent catalytic properties and the reactions went to completion, within 1-2 min to give products in high yield (90-98%). The catalyst is recoverable quantitatively and re-cycled with almost consistent activity. This new nano catalyst has the advantages of higher yield, lower cost, reduced environmental hazards, and the procedure is highly convenient. Graphical Abstract: Nano-MgO was prepared and characterized by PXRD, SEM, BET and TEM analyses. It was used for the study of microwave-assisted N-formylation of various amines with formic acid under solvent-free condition.

Full text of DOI:10.1007/s10562-010-0372-6

Catal Lett (2010) 138:82–87
DOI 10.1007/s10562-010-0372-6
Nano-MgO: An Efficient Catalyst for the Synthesis of Formamides
from Amines and Formic Acid Under MWI
•
M. B. Madhusudana Reddy S. Ashoka
•
•
G. T. Chandrappa M. A. Pasha
Received: 29 March 2010 / Accepted: 9 May 2010 / Published online: 25 May 2010
Ó Springer Science+Business Media, LLC 2010
Abstract Nano-MgO a basic catalyst was prepared by
solution combustion technique. It was characterized by
powder XRD, SEM, BET and TEM analyses. It was used
as a catalyst for the study of microwave-assisted N-
formylation of various aromatic and alkyl amines with
formic acid under solvent-free conditions. Nano-MgO
showed excellent catalytic properties and the reactions
went to completion, within 1–2 min to give products in
high yield (90–98%). The catalyst is recoverable quanti-
tatively and re-cycled with almost consistent activity. This
new nano catalyst has the advantages of higher yield, lower
cost, reduced environmental hazards, and the procedure is
highly convenient.
substituted arylimidazoles [7], 1,2-dihydroquinolines [8],
and nitrogen-bridged heterocycles [9] also require
formamides.
A number of formylating reagents as well as methods
are available in the literature [10–24]. Acetic formic
anhydride is a well known formylating reagent [10], but is
sensitive to moisture. Formylation using chloral [11],
activated formic acid in the presence of DCC [2], or EDCI
[12], activated formic esters [13–15], ammonium formate
in acetonitrile [16, 17], 2,2,2-trifluoroethyl formate [18],
formic acid [19], ZnO [20] and polyethylene glycol [21,
22] have been used for this purpose. More recently, Akbari
et al. [23] have reported catalyst-free N-formylation of
amines using guanidine derived ionic liquids. Most of the
available methods have limitations such as long duration,
high temperature, and use of expensive, toxic reagents or
catalysts.
Keywords Nano-MgO ꢀ Amines ꢀ Formic acid ꢀ
N-Formylation ꢀ Neat reaction ꢀ Microwaves
Microwave irradiation has been employed for a number
of organic reactions to reduce the reaction rate and gain
selectivity in the product formation, and to get products in
high yields [24].
1 Introduction
Formyl group has been used widely as amino-protecting
group in peptide synthesis and formamides are important
intermediates in organic synthesis [1]. They are used as
precursors for the synthesis of isocyanide [2, 3], as inter-
mediates for mono-methylation of primary amines [4] and
in the synthesis of formamidines [5]. Other pharmaceuti-
cally important compounds such as fluoroquinolines [6],
Further, nano sized particles are considered to be par-
ticularly attractive as catalysts for their high reactivity, due
to larger surface area [25–27]. They can be easily recov-
ered from the reaction mixture and recycled after activa-
tion, thereby rendering the process economically viable.
Among heterogeneous basic catalysts, nano-MgO is a sta-
ble, non-volatile, non-hygroscopic, odourless, and white
crystalline solid.
In continuation of our work on the development of
efficient and environmentally friendly methods for the
synthesis of various organic compounds [28–33], in this
paper the study of the activity of nano-MgO as a novel and
eco-friendly heterogeneous catalyst for the N-formylation
of various amines by formic acid under solvent-free
M. B. M. Reddy ꢀ S. Ashoka ꢀ G. T. Chandrappa ꢀ
M. A. Pasha (&)
Department of Studies in Chemistry, Bangalore University,
Central College Campus, Bengaluru 560001, India
e-mail: m_af_pasha@ymail.com
123

Nano-MgO: An Efficient Catalyst for the Synthesis of Formamides
83
R''
microwave irradiation is presented (Scheme 1). For com-
parison, bulk-MgO catalysts were also studied.
R''
Nano-MgO
+
N
3
+
H2O
HCOOH
2
NH
1
R'
O
MW/320W, 1-2 min
Neat
R'
R' = aryl, alkyl
R''= H, aryl, alkyl
Yield 90-98%
2 Experimental
Scheme 1 N-Formylation of amines with formic acid and nano-MgO
under MWI
2.1 Materials and Methods
The chemicals used were commercial reagents. All the
reactions were carried out in a MILESTONE microwave
reactor at 320 W. Melting points were determined using a
Bu¨chi apparatus. Nuclear magnetic resonance spectra were
obtained on a 400 MHz Bruker AMX spectrometer in
DMSO-d6 using TMS as a standard. GC-Mass spectra were
obtained using a Shimadzu GC-MS QP 5050A instrument
equipped with a 30 m length and 0.32 mm dia BP-5 col-
umn with the column temperature 80–15–250 °C. Infrared
spectra were recorded using Shimadzu FT-IR-8400s
Spectrometer as KBr pellets for solids and as thin films
between NaCl plates in case of liquids. Powder X-ray
diffraction data were obtained using Philips X’pert PRO X-
ray diffractometer using Cu Ka radiation. Morphology of
the MgO was examined by JEOL-JSM-6490 LV scanning
electron microscope (SEM) and Hitachi-H-8100 transmis-
sion electron microscope (accelerating voltage up to
200 kV, LaB6 filament) equipped with EDS (Kevex Sigma
TM Quasar, USA). Surface area and porosity of nano-MgO
was determined using gas sorption analyzer Quanta
Chrome Corporation NOVA 1000.
Fig. 1 Powdered XRD pattern of nano MgO particles
2.2 Synthesis of Catalyst
Nano-MgO particles were prepared by solution combustion
technique [34]. An aqueous solution of Mg(NO3)2ꢀ6H2O
and NH2CH2COOH (corresponding F/O ratio of 1.75 (u))
was taken in a petri dish. It was heated to obtain a semi-
solid. The dish was then introduced into a muffle furnace
maintained at 400 10 °C. Initially the semisolid
Fig. 2 SEM photograph of nano-MgO particles
Fig. 3 a TEM micrograph and
b SAED pattern of nano MgO
123

84
M. B. M. Reddy et al.
undergoes dehydration and then smoldering combustion
occurs at one end which quickly and propagates throughout
the mass. A voluminous black porous nanocrystalline
product results which becomes white on leaving it in the
muffle furnace at the same temperature for another 30 min.
Table 1 N-Formylation of amines with formic acid using nano-MgO
under solvent-free MWI
Entry Amine (1)
Producta (3)
Time (Sec)
60
b (%)
Yield
H
N
NH2
a
b
c
98, 45,c 50,d tracee
O
O
O
O
H
N
2.3 Characterization of Catalyst
NH2
NH2
NH2
80
90
98
95
The crystallinity of the nano-MgO was examined by
powder X-ray diffraction. The powdered XRD peaks
shown in Fig. 1 could be indexed to the cubic crystal
H
N
˚
system cell constant a = 4.22 A in good agreement with
the reported data [JCPDS: 75-0447]. The broadness of
peaks indicates the nano-crystalline nature of MgO. The
particle size of the nano-MgO powder was estimated using
Scherrer’s formula [35].
H
N
d
100
92
MeO
MeO
Kk
Crystallite size ¼
b cos h
O
NH2
N
H
e
f
95
60
98
97
where K is the Scherrer’s constant (0.9), k the wavelength
˚
of X-rays (1.541 A), and b is the full width half maxima.
H
N
The particle size was found to be in the range of 12–23 nm.
The SEM (Fig. 2) photographs reveals that the pow-
dered sample is porous, agglomerated with polycrystallite
nanoparticles. The occurrence of pores and voids can be
attributed to the gases escaping out of the reaction mixture
during combustion. TEM micrograph (Fig. 3a) exhibits
randomly oriented nanocrystalline MgO particles. The
selected area electron diffraction (SAED) pattern of the
sample (Fig. 3b) shows reflections corresponding to (111),
(200), (220) and (222) planes, supporting the presence of
MgO in cubic crystalline phase.
NH2
O
O2N
O2N
H
N
Cl
NH2
Cl
g
h
110
120
93
92
O
Cl
Cl
H
N
NH2
O
O
H
N
NH2
i
70
95
2.4 Catalytic Activity: Microwave-Irradiated
N-Formylation of Amines Under Solvent
Free Conditions
HO
HO
HO
HO
H
NH2
NH2
NH2
N
A mixture of aniline (2 mmol), formic acid (3 mmol) and
nano-MgO (20 mg) was taken in a Pyrex glass tube,
homogenized and placed in a microwave reactor. It was
irradiated (320 W) for 1 min with 20 s intervals (Table 1,
entry a). After the completion of the reaction [as indicated
by TLC], EtOAc (5 mL) was added to the reaction mixture.
Nano-MgO was removed by filtration. The reaction mix-
ture was then taken into a separating funnel and washed
with water (3 9 5 mL), saturated solution of NaHCO3
(5 mL), and again with water (5 mL) and dried over
anhydrous MgSO4, and the solvent was removed under
vacuum to get the solid product. The solid product thus
obtained was purified by recrystallization using ether or
CHCl3. Products were characterized by melting point,
j
80
85
94
91
O
OH
OH
H
N
k
O
H
N
O2N
O2N
l
70
85
94
O
NO2
NO2
m
90
H
N
NH2
O
1
FT-IR and H NMR spectra.
123

Nano-MgO: An Efficient Catalyst for the Synthesis of Formamides
85
Table 1 continued
Nano-MgO
Bulk-MgO
100
80
60
40
20
0
Entry Amine (1)
Producta (3)
Time (Sec)
90
b (%)
Yield
H
N
n
98
NH2
O
O
O
O
H
N
NH2
o
p
110
120
95
90
O
O
OH
OH
O
H
N
N
a
All reactions were performed using an amine (2 mmol), formic acid
(3 mmol) and nano-MgO (20 mg)
10
20
30
40
50
60
70
80
Reaction time (Sec)
b
Isolated yield, and all the compounds are known and physical
properties agree with the reported values; IR and Mass spectral data
matches with the reported data; and compounds 3a–3f were charac-
Fig. 4 Pictorial presentation of the catalytic activity of nano-MgO
with bulk-MgO
1
terized by H NMR spectral analysis
c
Bulk MgO
reaction mixture were collected periodically at an interval
of 20 s and analyzed by GC-MS. Figure 4 shows the var-
iation of the percentage conversion of amine to the product
with time, when nano-MgO and bulk-MgO were employed
as catalysts. Results of this study are presented in Table 2.
It is evident that, the catalytic activity of the nano-MgO is
much greater than that of the bulk-MgO. After 1 min nano-
MgO showed 98% conversion of the amine as compared to
45% with bulk-MgO. The increased catalytic activity of
nano-MgO over the bulk-MgO may be attributed to the
higher surface area of nano-MgO (SA: 37 m2 g-1). The
catalytic activity of nano-MgO was also evident from the
fact that, in the absence of the catalyst no product was
obtained. The effect of microwave irradiation over con-
ventional heating was demonstrated from the fact that
when a mixture of 1a and 2 on heating in the presence of
d
Heated at 100 °C, 30 min
Without catalyst
e
3 Results and Discussion
Initially, we carried out a reaction between aniline (1,
2 mmol) and formic acid (2, 3 mmol) in the presence of
nano-MgO (20 mg) under solvent-free MW irradiation and
N-formamide in 98% yield was obtained (Table 1, entry a).
In order to further investigate the scope of this reaction,
under similar reaction conditions, a variety of substituted
anilines and formic acid were subjected to MW irradiation
in the presence of catalytic amount of nano-MgO and the
results are presented in Table 1. Aniline derivatives with
electron-donating or electron-withdrawing substituents
such as alkyl (entries b and c), chloro (entries g and h)
methoxy (entry d), hydroxy (entries i, j and k) and nitro
groups (entries f, l and m), gave the corresponding products
in excellent yield. Further, benzylamine (entry e) also gave
the corresponding formamide in 98% yield under similar
experimental condition. The formation of formamides was
confirmed by IR spectral analysis, which showed two
characteristic peaks, one between 3,300 and 3,400 cm-1
(secondary NH) and the other between 1,640 and
Table 2 Comparison of the catalytic activity of nano-MgO with
bulk-MgO
Entry
Time (s)
% of yielda
Nano-MgO
Bulk-MgO
a
b
c
d
e
f
10
20
30
40
50
60
70
80
20
35
45
70
80
98
98
98
0
5
1,680 cm-1 (N-formyl, C=O). The H NMR spectra of the
1
15
25
35
45
45
45
N-formamides showed one amide NH proton signal
between d 10–11 ppm; and another signal between d
8–9 ppm for the aldehydic proton.
g
h
The catalytic activity of the nano-MgO particles was
compared with that of the commercially available bulk-
MgO. For this purpose, the reactions were carried out
separately under solvent-free MW irradiation at 320 W
with both the catalysts for 1–2 min. The aliquots of the
Isolated yield
a
Reaction conditions: A mixture of amine (2 mmol), formic acid
(3 mmol) and 20 mg of catalyst under solvent-free and MWI
123

86
M. B. M. Reddy et al.
Yield (%) [Ref.]
Table 3 Comparison of nano-
MgO catalyzed N-formylation
with other methods
Entry
Formylation reagent/catalyst/solvent/condition
Time (h/min)
a
b
c
d
e
f
HCOOH/PEG-400/RT
4–6 h
79–93 [23]
25–99 [17]
60–99 [21]
94–98 [24]
63–91 [18]
90–98a
Ammonium formate/Toluene/heat
HCOOH-ZnO/heat (70 °C)
HCOOH/IL/RT
4–9 h
10–720 min
5–30 min
12 h
a
Reaction conditions: aromatic
amine (2 mmol), formic acid
(3 mmol) and nano-MgO
(20 mg), MW (320 W) under
solvent-free condition
NH4COOH/Neat/CH3CN-reflux
HCOOH/nano-MgO/solvent-free-MWI
1–2 min
O
N
H
H
Scheme 2 Plausible
mechanism for the N-
formylation of amines on nano-
MgO surface
O
H
H
O
Ph
H
H
O
H
+
N
H
H
H
Ph
O
Ph
Ph
+
H
N
_
N
. .
O
H
O
H
O
H
H
H
2+
Mg
2-
O
2-
O
2-
O
2-
O
2-
O
2-
O
2-
O
2-
O
2+
Mg
2-
O
2+
Mg
2+
Mg
2+
Mg
2+
Mg
2+
Mg
2+
Mg
catalytic nano-MgO at 100 °C for about 30 min, gave the
corresponding formamide in low yield (3a, 50%).
(90–98%) of high purity and the reusability of the solid basic
catalyst after separation followed by thermal activation.
When compared with other reported methods (Table 3,
entries a–e with f), we have found, nano-MgO to be an
efficient catalyst for the rapid synthesis of formamides in
excellent yields within 1–2 min, under solvent-free MWI;
the results of this study are presented in Table 3.
Acknowledgements G.T.C. gratefully acknowledges the financial
support from the Department of Science and Technology, NSTI
Phase-IV, Government of India, New Delhi. We also acknowledge
the help of Prof. Jai Prakash, Bangalore Institute of Technology, for
providing surface area measurement facility and MW reactor. One of
the authors M.S. Reddy also wishes to thank Dr. D.N. Sathyanara-
yana, Professor (Retired) Department of Inorganic and Physical
Chemistry, I. I. Sc, Bengaluru, India, for constant encouragement.
3.1 Recyclability of the Catalyst
Reusability of the catalyst was examined employing the
reaction between 1a and 2 to obtain 3a under identical
reaction conditions. The catalyst was easily recovered from
the mixture by filtration. It was washed with distilled water
and ethyl acetate repeatedly, and dried for 2–3 h under
vacuum. The recycled catalyst was used five times to
obtain N-formamide without appreciable decrease in the
yield 98, 93, 95, 90 and 95%, respectively, for 1–5 cycles.
After every reaction, the catalyst was recovered from the
reaction mixture and regenerated as described above.
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In conclusion, nano-MgO is an active and reusable catalyst
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The significance of the study lies in the solvent-free eco-
nomical synthesis of N-formamides in excellent yield
123

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87
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