Sulfamic acid functionalised magnetic nanoparticles: An efficient solid acid for the multicomponent condensations

Article abstract of DOI:10.3184/174751912X13264749420957

Sulfamic acid-functionalised magnetic nanoparticles have been synthesised and used as efficient heterogeneous solid acid catalysts for the condensation of aromatic aldehydes with 2-naphthol and amides (or carbamates) via three-component reactions under solvent-free conditions at 80°C. Quantitative conversion of the reactants is achieved under mild conditions. Recovery of the catalyst is easily achieved by 'magnetic decantation'. The supported catalyst is reused four times without any significant degradation in catalytic activity.

Full text of DOI:10.3184/174751912X13264749420957

52 RESEARCH PAPER
JANUARY, 52–55
JOURNAL OF CHEMICAL RESEARCH 2012
Sulfamic acid functionalised magnetic nanoparticles: an efficient solid
acid for the multicomponent condensations
Hossein Yarahmadi and Hamid Reza Shaterian*
Department of Chemistry, Faculty of Sciences, University of Sistan and Baluchestan, PO Box 98135-674, Zahedan, Iran
Sulfamic acid-functionalised magnetic nanoparticles have been synthesised and used as efficient heterogeneous
solid acid catalysts for the condensation of aromatic aldehydes with 2-naphthol and amides (or carbamates) via
three-component reactions under solvent-free conditions at 80 °C. Quantitative conversion of the reactants is achieved
under mild conditions. Recovery of the catalyst is easily achieved by ‘magnetic decantation’. The supported catalyst
is reused four times without any significant degradation in catalytic activity.
Keywords: sulfamic acid, amidoalkyl naphthols, heterogeneous catalyst, magnetic decantation, solvent-free conditions,
multicomponent reactions, nanoparticles
In synthetic organic chemistry, multicomponent reactions
(MCRs) have gained considerable popularity in recent years
due to their flexible, convergent, and atom-efficient nature.
The MCRs are an ideal synthetic tool to generate multiple
molecular scaffolds and to increase structural and skeletal
diversity.1
agents.25 In continuation of our research on the application
of heterogeneous catalysts in organic reactions,26–31 we
have employed SA-MNPs in preparation of AAN and CANs
(Scheme 1).
Results and discussion
Surface functionalised iron oxide magnetic nanoparticles
(MNPs) have emerged as feasible substitutes to conventional
materials as robust, active, high-surface-area catalyst supports
for one-pot MCR condensations.2–10 In view of their nano-size,
the contact between reactants and catalyst increases dramati-
cally thus mimicking the homogeneous catalysts.11 The mag-
netic nature of these particles allows for easy recovery and
recycling of the catalysts by an external magnetic field, which
may optimise operational cost and enhance product purity.12
Consequently, there has been considerable interest in the
development of stable, reusable, and highly active solid
acids13 as environmentally benign replacements for their
homogeneous counterparts.
During the last few years, sulfamic acid (NH2SO3H, SA),
a dry nonhygroscopic, nonvolatile, and odourless solid has
been considered as an efficient heterogeneous catalyst sub-
stitute for conventional acidic catalysts.14–20 In this study, we
report sulfamic acid-functionalised magnetic nanoparticles
(SA-MNPs) as efficient heterogeneous catalysts for the
one-pot synthesis of amido-alkyl naphthols (AANs) and car-
bamato-alkyl naphthols (CANs) via three-component cou-
plings of aldehydes, amides (or carbamates) and 2-naphthol
in solvent-free conditions.
Our initial study focused on the development of the optimal
reaction conditions for this transformation. To determine
the best weight of the catalyst and temperature, as shown in
Table 1, syntheses were carried out in the presence of different
amounts of catalyst and at different temperatures. Initially, the
reaction was studied without any catalyst at 120 °C but only
afforded a poor yield (14%) of the final product (Table 1, entry
1). Table 1 shows a remarkable increase in yields according
to the increase in the quantity of catalyst and temperature.
In order to use the minimum mass of the catalyst and
temperature, we have been limited to 20 mg mol−1 of catalyst
at 80 °C for the continuation of this study to determine opti-
mum conditions (Table 1, entry 12) for synthesis of a variety
of substrates. The results are summarised in Table 2.
As can be seen from Table 2, electronic effects and the
nature of the substituent on the aromatic rings showed clear
effects in terms of reaction time under the reaction conditions
mentioned. In all of the cases, the corresponding AANs and
CANs were obtained in good to excellent yields. Aromatic
aldehydes substituted by electron-donating groups (EDG)
(Table 2, entries j–o) require a longer reaction time than those
of electron-withdrawing groups (EWG) (Table 2, entries b–h).
While meta- and para-substituted aldehydes gave good results,
ortho-substituted aldehydes require a longer time because
of the steric effects. We also used benzamide and methyl, ethyl
or benzyl carbamates instead of acetamide in the mentioned
reaction and the corresponding products were obtained in good
to excellent yield with short reaction times. Under the same
conditions, this reaction did not proceed when heterocyclic
2-pyridinecarbaldehyde (Table 2, entry i) and aliphatic alde-
hydes such as propionaldehyde or heptaldehyde (Table 2,
entries p, q) were used as the starting material.
AANs and CANs as precursors have been used for pre-
paration of a variety of biologically important natural products
and potent drugs including a number of nucleoside antibiotics
and HIV protease inhibitors, such as ritonavir and lipinavir.21
The hypotensive and bradycardiac effects of these compounds
have been evaluated.22 The intramolecular cyclisation of AANs
by Vilsmeier reagents produce 1,3-oxazines.23 The synthesis of
1,3-oxazines has attracted attention because of their potential
as antibiotics,22 anti-hypertensive,24 and potent anti-rheumatic
Scheme 1 Preparation of AANs and CANs.
* E-mail: hshaterian@yahoo.com; hshaterian@chem.usb.ac.ir

JOURNAL OF CHEMICAL RESEARCH 2012 53
Table 1 Catalyst and temperature screening for the synthesis
of 9a,b
Table 2 Synthesis of amidoalkyl naphthol drivatives catalysed
by SA-MNPs under solvent free conditionsa
Entry
Temperature/°C
Catalyst/mg
Yield of 9/%c
1
2
100
35
–
14
68
76
82
91
93
93
92
90
91
92
93
88
81
73
200
200
200
200
200
200
150
100
50
3
50
4
65
80
Entry X
R
Product Time /min Yield /%a
Ref.
5
6
100
120
80
a
H
A
B
C
D
E
1
2
3
4
5
5
3
10
10
15
90
88
82
83
80
26, 32
30
29
—
29
7
8
9
80
10
11
12
13
14
15
80
80
30
80
20
b
c
2-Cl
4-Cl
8
12
15
84
82
79
26
36
29
A
C
E
6
7
8
80
10
80
5
1
80
93
26, 32
A
B
C
D
9
10
11
12
3
3
8
a All reactions were conducted with 4-chlorobenzaldehyde
(1 mmol), 2-naphthol (1 mmol), acetamide (1.2 mmol) and
SA-MNPs in solvent-free conditions. b The time of all reactions
is 1 h. c Isolated yields.
90
86
82
30
29
—
10
d
2,4-Cl
91
89
26, 32
29
A
C
13
14
3
9
As reported in the literature,32 the reaction of 2-naphthol
with aromatic aldehydes in the presence of an acid catalyst is
known to give ortho-quinone methides (o-QMs) as highly
reactive and ephemeral intermediates. The same o-QMs, gen-
erated in-situ, have been reacted with amides to form the
desired derivatives. A reasonable explanation for this result
can be given by considering the nucleophilic addition to o-QM
intermediates favourable via conjugate addition on to the α,
β-unsaturated carbonyl group that aromatises to the naphtha-
lene ring of this intermediate. The EWD substitution on a
benzaldehyde in o-QM intermediates increases the rate of 1,4-
nucleophilic addition reaction because the alkene LUMO is at
lower energy in the neighbouring withdrawing groups than in
the case of an EDG example.26 The reactions of aliphatic alde-
hydes (Table 2, entries p, q) instead of aromatic aldehydes
were not completed and only gave the desired products with a
e
f
2-NO2
3-NO2
85
26, 32
26, 32
30
A
A
B
C
15
16
17
18
5
2
2
4
93
94
87
29
g
h
4-NO2
4-CN
2
5
5
91
86
81
26, 32
29
—
A
C
D
19
20
21
3
3
8
85
37
A
B
C
E
22
23
24
25
88
80
75
37
—
—
14
i
j
k
l
2-pyridine
30
-
—
—
29
A
D
C
A
26
27
28
29
2,4-OMe
2,5-OMe
3,4-OMe
12
15
15
77
81
80
26, 32
low yield as well as observed also with the known catalysts,
m
4-Me
73
72
26
30
A
B
30
31
20
20
33
such as K5CoW12O40 3H2O, p-TSA,34 and cation-exchange
.
resins,35 probably due to the lower stability of o-QMs from
aliphatic aldehydes.
n
o
4-OMe
3-OMe
35
65
26, 32
A
32
Efficiency and recovery are the key factors which limit
applications of catalysts in synthetic chemistry and industrial
processes. The recycling of SA-MNPs catalyst was then
investigated. After each reaction, dichloromethane (5 mL) was
added to the reaction mixture and an external magnetic field
was applied on the outer surface of the glass reaction contain-
ing the SA-MNPs using a permanent magnet. While the exter-
nal magnet held the SA-MNPs stationary inside the vessel, the
reaction solution was easily decanted and separated from the
catalyst (Fig. 1).
15
20
30
86
83
80
26
—
29
A
C
E
33
34
35
p
q
ethyl
n-hexyl
60
60
trace
trace
—
—
A
A
36
37
a Yields refer to the isolated pure products. The reaction was
carried out under thermal solvent-free conditions in an oil bath
at 80 °C.
A heterogeneous catalyst is more interesting when it can be
re-used. For this purpose, the synthesis of 9 was carried out
using fresh and recovered SA-MNPs catalyst for a four-cycle
run. The recovered catalyst was washed with acetone, dried
at 100 °C and was reused. The obtained yields after the four-
cycle runs is almost unchanged (92, 90, 86 and 83%) which
demonstrates that SA-MNPs can be easily recovered and
re-used without any loss of their activity.
A comparison for the efficiency of the catalytic activity
of SA-MNPs with several previous methods is presented in
Table 3. The results show that this method is superior to some
of the earlier methods in terms of yields and reaction times.
In conclusion, we have developed a simple, efficient, and
green methodology for the synthesis ofAANs and CANs using
sulfamic acid magnetic nanoparticles (SA-MNPs) under
solvent-free conditions at 80 °C. The simple experimental

54 JOURNAL OF CHEMICAL RESEARCH 2012
Table 3 Comparison of catalytic activity of SA-MNPs with
several known catalystsa
Entry Catalyst Conditions
Time Yield /% Ref.
1
2
3
4
5
6
Ce(SO4)2 MeCN, Reflux, 85 °C 36 h
72
87
89
93
86
90
32
38
39
27
28
I2
Solvent-free, 125 °C
4.5 h
1.5 h
50 min
K-10 clay Solvent-free, 125 °C
Fe(HSO4)3 Solvent-free, 85 °C
FeCl3.SiO2 Solvent-free, 120 °C 11 min
SA-MNPs Solvent-free, 80 °C 5 min
This
work
a Reaction conditions: benzaldehyde (1 mmol), 2-naphthol
(1 mmol), acetamide (1.2 mmol).
Synthesis of N-((4-chlorophenyl)(2-hydroxynaphthalen-1-yl)methyl)
acetamide (9)
A mixture of a 4-chlorobenzaldehyde (1 mmol), 2-naphthol (1 mmol),
acetamide (1.2 mmol) and 20 mg of sulfamic acid-functionalised
magnetic nanoparticles (SA-MNPs) as catalyst was vigorously stirred
at 80 °C for the specific time (3 min). The end of the reaction was
monitored by TLC. After completion, the mixture reaction was diluted
by dichloromethane (5 mL); then the catalytic system was removed by
an external magnet and reused as such for the next experiment. The
organic layer was washed with aqueous solution of 10% NaHCO3 and
water, dried with Na2SO4 and concentrated to give the crude products.
Consequently the desiredAAN was purified by a recrystallisation pro-
cedure using aqueous EtOH (15%); yield: 93%; m.p. 222–224 °C
Fig. 1 The attention of magnetic nanoparticles (MNPs) sus-
pended in water by a conventional magnet in about 5 min.
1
(lit.26 223–225 °C); H NMR (DMSO-d6): δ = 1.96 (s, 3H), 7.05 (d,
J = 8.1 Hz, 1H), 7.11 (d, J = 8.6 Hz, 2H), 7.18 (d, J = 8.6 Hz, 1H),
7.19 (m, 3H), 7.31 (t, J = 7.5 Hz, 1H), 7.73 (m, 3H), 8.42 (d, J =
8.6 Hz, 1H), 10.09 (s, 1H) ppm; 13C NMR (DMSO-d6): δ = 20.6, 23.1,
48.1, 118.9, 119.0, 123.0, 126.9, 128.9, 128.4, 129.1, 129.1, 130.0,
131.2, 132.7, 142.3, 153.7, 169.9 ppm.
Electronic Supplementary Information
The general procedure, spectral data of representative unknown
1
AANs and CANs and copies of FT-IR, H and 13C NMR and
mass spectra for all unknown compounds are given in the ESI
available through stl.publisher.ingentaconnect.com/content/
stl/jcr/supp-data.
We are thankful to the University of Sistan and Baluchestan
Research Council for the partial support of this research.
Received 20 November 2100; accepted 9 January 2012
Paper 1100995 doi: 10.3184/174751912X13264749420957
Published online: 31 January 2012
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