Catalytic activity of magnetic Fe3O4@Diatomite earth and acetic acid for the N-acylation of sulfonamides

Article abstract of DOI:10.1016/j.tetlet.2015.12.044

The Br?nsted and Lewis acidic promoted N-acylation of sulfonamides with acetic anhydride or benzoyl chloride has been achieved using glacial acetic acid and magnetic Fe₃O₄@Diatomite earth. Use of acetic acid as solvent omits the need for organic bases and permits the isolation of products by filtration and precipitation. Additionally, the magnetic composite Fe₃O₄@Diatomite acts as a conjugate proton super acid, enabling the acylation of sulfonamide compounds.

Full text of DOI:10.1016/j.tetlet.2015.12.044

Tetrahedron Letters xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Catalytic activity of magnetic Fe3O4@Diatomite earth and acetic acid
for the N-acylation of sulfonamides
b
Mohammad Hadi Ghasemi a, Elaheh Kowsari a, , Seyed Kiumars Hosseini
⇑
a Department of Chemistry, Amirkabir University of Technology, Hafez Avenue, No. 424, PO Box 159163-4413, Tehran, Iran
b Temad Co., R&D Laboratories, PO Box 316481-6478, Karaj, Tehran, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
The Brønsted and Lewis acidic promoted N-acylation of sulfonamides with acetic anhydride or benzoyl
chloride has been achieved using glacial acetic acid and magnetic Fe3O4@Diatomite earth. Use of acetic
acid as solvent omits the need for organic bases and permits the isolation of products by filtration and
precipitation. Additionally, the magnetic composite Fe3O4@Diatomite acts as a conjugate proton super
acid, enabling the acylation of sulfonamide compounds.
Received 20 February 2015
Revised 26 November 2015
Accepted 8 December 2015
Available online xxxx
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Diatomite earth
Glacial acetic acid
Magnetic Fe3O4
N-acylation
Sulfonamide
N-Acyl sulfonamides are best known as bacteriostatic and anti-
malarial agents1 and are also present in a range of drugs possessing
various pharmacological activities. Acylated sulfonamides are
found in several recently developed therapeutic agents for Alzhei-
mer’s disease,2 t-RNA synthesis inhibition,3 antagonists of Angio-
tensin II,4 prostaglandin Fla sulfonamides which may have use in
the treatment of osteoporosis and Luekotriene D4-receptors.5,6
The N-acyl sulfonamide group has shown significant potential for
use in biological applications.7–9 They are suitable carboxylic acid
replacements and have been used as enzyme inhibitors due to
their acidity and resistance to chemical and enzymatic hydroly-
sis.10 Generally, N-acyl sulfonamides are synthesized by the acyla-
tion of easily accessible primary sulfonamides11–13 using acid
anhydrides, esters or acid chlorides in basic reaction media using
trialkylamines, pyridine,14,15 alkali hydroxides16 or other bases.17
The N-acylation of sulfonamides can also be performed under
acidic conditions. For example, concentrated H2SO4 in acetonitrile
has been used to promote the N-acylation of sulfonamides.18 How-
ever, the use of highly acidic catalysts has potential problems relat-
ing to the corrosive acid waste of which handling presents
undesirable economic and environmental issues and raises a num-
ber of health and safety issues.
oped using solid Lewis acids, such as mesoporous aluminosili-
cas,20,21 nanoclay,22 zeolites and resin.23 The use of porous
materials such as zeolites is often limited by their pore size, which
prevent larger molecules from reaching the active sites. Hence,
there is still need for new catalysts which can overcome this prob-
lem. An ideal catalyst would act in a heterogeneous manner, be
chemically and thermally stable, and easily available. Recently,
researchers have focused their efforts on the application of metal
or metal oxide nanoparticles as novel catalysts due to their high
catalytic activities and improved selectivities.24,25 Although
nanocatalysts have several advantages over conventional catalyst
systems, the isolation and recovery of these are difficult. To over-
come this problem, the use of magnetically recoverable nanocata-
lysts which can be easily separated from reaction mixtures using
an external magnetic field is of significant interest.26 Amongst cat-
alysts derived from heavy or rare metals, those featuring iron ben-
efit from its high abundance and consequent lost cost. Hence, iron
based catalysts, especially magnetic Fe3O4, have experienced
increased use as metal-based reaction promoters, especially those
that can be applied in catalytic amounts and/or are recyclable.27,28
Recently, attention has been focused on the utilization of mixed
Lewis and Brønsted acids catalysts which can act as conjugate pro-
ton super acids.29 In this research, magnetic Fe3O4@Diatomite
earth composite, prepared by an in situ co-precipitation method
with the assistance of ultrasound irradiation, was used as an effi-
cient and easy separable catalyst for N-acylation and was com-
pared with the catalytic activity of acetic acid (Scheme 1).
Several Lewis acids, such as BF3ÁEt2O, ZnCl2, MoCl5, TiCl4, B
(C6F5)3, Sc(OTf)3 and I2, have been used to catalyze the N-acylation
of sulfonamides.19 Additionally, catalytic systems have been devel-
⇑
Corresponding author.
http://dx.doi.org/10.1016/j.tetlet.2015.12.044
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Ghasemi, M. H.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.12.044

2
M. H. Ghasemi et al. / Tetrahedron Letters xxx (2015) xxx–xxx
(CH3CO)2O
SO2NHCOCH3
CH3COOH
HCl
+
+
R
R
a) CH3COOH, 50 °C, 2 h
SO2NH2
b) Fe3O4@DE, THF, 50 °C, 1 h
R
SO2NHCOPh
PhCOCl
Scheme 1. N-acylation of sulfonamides with acetic anhydride or benzoyl chloride.
Table 1
N-acylation of N-(4-sulfamoylphenyl)acetamide with acetic anhydride using different catalystsa
(CH3CO)2O
Catalyst
AcHN
SO2NH2
AcHN
SO2NHCOCH3
+ CH3COOH
Yieldb (%)
Entry
Catalyst
Time (h)
T (°C)
1
2
3
4
5
6
7
8
—
8
8
8
8
8
8
8
8
2
2
1
rt
rt
rt
rt
rt
rt
rt
rt
rt
50
50
–
FeCl3Á6H2O
Trace
Trace
53
45
63
65
78
71
95
Fe2O3
Fe3O4
CoFe2O4
Diatomaceous Earth (DE)
CoFe2O4@DE
Fe3O4@DE
Fe3O4@DE
Fe3O4@DE
Fe3O4@DE
9
10
11
93
a
Reactions conditions: THF (10 mL), sulfonamide (0.86 g, 4 mmol, 1 equiv), acetic anhydride (0.41 g, 4 mmol, 1 equiv),
catalyst (3 mol %).
b
Isolated yield.
Table 2
N-acylation of N-(4-sulfamoylphenyl)acetamide with benzoyl chloride using different catalystsa
PhCOCl
Catalyst
AcHN
SO2NH2
AcHN
SO2NHCOPh
+ HCl
Entry
Catalyst
Time (h)
T (°C)
Yieldb (%)
1
2
3
4
5
6
7
8
9
10
—
8
8
8
8
8
8
8
8
2
1
rt
rt
rt
rt
rt
rt
rt
rt
rt
50
–
FeCl3Á6H2O
32
37
48
43
64
68
75
70
95
Fe2O3
Fe3O4
CoFe2O4
Diatomaceous Earth (DE)
CoFe2O4@DE
Fe3O4@DE
Fe3O4@DE
Fe3O4@DE
a
Reactions conditions: THF (10 mL), sulfonamide (0.86 g, 4 mmol, 1 equiv), benzoyl chloride (0.56 g, 4 mmol, 1 equiv),
catalyst (3 mol %).
b
Isolated yield.
Initially, the model N-acylation reactions of N-(4-sulfamoyl-
–Cl, –Br, –Me, –NO2 and –COOH as well as methanesulfonamide
were reacted with acetic anhydride and benzoyl chloride30 under
acetic acid or Fe3O4@DE catalysis and the results are summarized
in Tables 3 and 4. The catalytic activities of both catalysts were good
and in most cases, the heterogeneous catalyst gave better yields
than the acetic acid solvent system (Tables 3 and 4). Excellent yields
in the N-acylation reactions can be related to stabilization of the
highly polar acylium intermediate with acetic acid as a polar sol-
vent and Fe3O4@DE as a Lewis acid catalyst. The main advantages
of using Fe3O4@DE as a heterogeneous catalyst compared to acetic
acid as a homogeneous catalyst were the higher efficiencies and
simple catalyst recycling at the end of the reaction. The desired
sulfonamides were easily isolated in good yields and purities by
phenyl)acetamide with acetic anhydride and benzoyl chloride were
examined. A comparison with the performance of some of the var-
ious heterogeneous catalysts clearly showed that the yields using
Fe3O4@DE were higher (Tables 1 and 2). In addition, in the presence
of Fe3O4@DE, the reactions were carried out using reduced times.
An increase in the temperature up to 50 °C caused a significant
increase in the efficiency of the reaction resulting in higher yields
with short reaction times. Tables 1 and 2 clearly indicate that the
Fe3O4 magnetic nanoparticles having Lewis acid character on the
outer surfaces of the Diatomite earth help catalyze the N-acylation
reaction. Having established optimized conditions, aryl sulfon-
amides containing different functional groups; –NHCOCH3, –OMe,
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M. H. Ghasemi et al. / Tetrahedron Letters xxx (2015) xxx–xxx
3
Table 3
N-acylation of sulfonamides with acetic anhydride
Entry
RSO2NH2
N-Acylsulfonamide
Yielda (%)
CH3COOHb
Fe3O4@DEc
O
AcHN
O
S
AcHN
NH
1
95
93
O
a1
O
O
S
NH
2
3
4
5
90
85
85
80
95
95
93
95
O
a2
O
Cl
O
S
Cl
NH
O
a3
O
H3C
O
H3C
S
NH
O
a4
O
MeO
O2N
O
MeO
O2N
S
NH
O
a5
O
O
S
NH
6
7
85
75
95
95
O
a6
HOOC
O
HOOC
O
S
NH
O
a7
O
Br
O
S
Br
NH
8
9
85
90
O
a8
O
O2N
Me
O
O2N
S
NH
80
95
88
97
O
a9
O
O
S
NH
10
O
a10
a
b
c
Isolated yield.
Reaction conditions: acetic acid (10 mL), sulfonamide (4 mmol, 1 equiv), acetic anhydride (0.41 g, 4 mmol, 1 equiv), 50 °C, 2 h.
Reaction conditions: THF (10 mL), sulfonamide (4 mmol, 1 equiv), acetic anhydride (0.41 g, 4 mmol, 1 equiv), Fe3O4@DE
(3 mol %), 50 °C, 1 h.
filtration of the precipitated solid from boiling water. This method
eliminates the use of expensive organic solvents and amine bases,
making the isolation and purification of the sulfonamide simple.
The magnetic catalyst has attractive properties, such as simple
manipulation and reusability. The catalyst could be easily isolated
by application of a magnetic field. The catalytic activity of the
catalyst remained unchanged after five reaction cycles, with each
cycle giving an excellent yield.31
In summary, we have demonstrated the glacial acetic acid and
Fe3O4@DE composite promoted N-acylation reactions of primary
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4
M. H. Ghasemi et al. / Tetrahedron Letters xxx (2015) xxx–xxx
Table 4
N-acylation of sulfonamides with benzoyl chloride
Entry
RSO2NH2
N-Acylsulfonamide
Yielda (%)
CH3COOHb
Fe3O4@DEc
O
AcHN
O
S
AcHN
NH
1
95
95
O
b1
O
O
S
O
b2
NH
2
3
4
80
90
80
96
95
95
O
Cl
O
S
Cl
NH
O
b3
O
H3C
O
S
H3C
NH
O
b4
O
MeO
O2N
O
MeO
O2N
S
NH
5
6
7
8
9
90
70
80
80
85
95
95
95
95
93
95
99
O
b5
O
O
S
NH
O
b6
HOOC
O
HOOC
O
S
NH
O
b7
b8
O
Br
O
S
Br
NH
O
O
O2N
H3C
O
O2N
S
NH
O
b9
O
O
S
NH
10
O
b10
a
b
c
Isolated yield.
Reaction conditions: acetic acid (10 mL), sulfonamide (4 mmol, 1 equiv), benzoyl chloride (0.56 g, 4 mmol, 1 equiv), 50 °C, 2 h.
Reaction conditions: THF (10 mL), sulfonamide (4 mmol, 1 equiv), benzoyl chloride (0.56 g, 4 mmol, 1 equiv), Fe3O4@DE
(3 mol %), 50 °C, 1 h.
sulfonamides. These procedures have the advantages of mild reac-
tion conditions, high yields, clean reactions, short reaction times,
and operational simplicity and recyclability, which make them
useful and attractive for the syntheses of N-acylated sulfonamide
derivatives.
Acknowledgment
The authors wish to gratefully thank the Research Affairs
Division at Amir Kabir University of Technology (AUT), Tehran
for financial support.
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M. H. Ghasemi et al. / Tetrahedron Letters xxx (2015) xxx–xxx
5
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30. General procedure for N-acylation: N-(4-Sulfamoylphenyl) acetamide (0.86 g,
4 mmol) was treated with acetic anhydride (0.41 g, 4 mmol) in glacial acetic
acid (10 mL). The mixture was stirred at 50 °C for 2 h and progress of the
reaction was monitored by TLC. After completion, the precipitate was collected
by filtration and washed with water. The impure precipitate was dissolved in
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a
white solid (0.97 g, 95%). The catalytic activities of the heterogeneous
catalysts were determined by the reaction with acetic anhydride or benzoyl
chloride. For example: N-(4-sulfamoylphenyl) acetamide (4 mmol) was treated
with acetic anhydride (4 mmol) in the presence of catalyst (3 mol %) in THF
(10 mL). After reaction completion, the catalyst was separated with an external
magnetic field and the solvent removed by a rotary evaporator. The precipitate
was dissolved in an aqueous solution of sodium carbonate (50 mL, pH = 8.0)
and filtered. Acetic acid was added dropwise to precipitate the product
(pH = 5.0) which was collected by filtration and was washed with distilled
water to afford N-(4-acetamidophenylsulfonyl)acetamide as a white solid. All
N-acylsulfonamides except compound b7 are known compounds and are
further characterized using mp, 1H NMR, 13C NMR, IR, MS and CHN analysis
(see ESI for complete details). 3-(N-Benzoylsulfamoyl)benzoic acid (b7);
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C
14H11NO5S; MW: 305; mp: 153–155 °C; 1H NMR (400 MHz, CDCl3) d(ppm):
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1H), 10.68 (br s, 1H); 13C NMR (100 MHz, CDCl3) d(ppm): 122.4, 122.9, 130.2,
(cmÀ1): 684,
ꢀ
t
135.5, 136.1, 137.7, 141.4, 143.9, 145.1, 155.7, 169.9, 170.1; IR
755, 871, 992, 1114, 1238, 1360, 1440, 1599, 1713, 2882, 2934, 3070, 3241,
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Please cite this article in press as: Ghasemi, M. H.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.12.044