Fe-exchanged montmorillonite K10 - The first heterogeneous catalyst for acylation of sulfonamides with carboxylic acid anhydrides

Article abstract of DOI:10.1016/j.tetlet.2004.04.077

Fe-exchanged montmorillonite K10 catalyzes a highly efficient reaction between sterically and electronically diverse sulfonamides and carboxylic acid anhydrides to furnish N-acylsulfonamides in excellent yield and high selectivity. The catalyst can also be reused several times.

Full text of DOI:10.1016/j.tetlet.2004.04.077

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 4805–4807
Fe-exchanged montmorillonite K10––the first heterogeneous
catalyst for acylation of sulfonamides with
carboxylic acid anhydrides
Devendrapratap U. Singh, Pankajkumar R. Singh and Shriniwas D. Samant*
Organic Chemistry Research Laboratory, University Institute of Chemical Technology,
N.M. Parekh Marg, Matunga, Mumbai 400 019, India
Received 26 January 2004; revised 1 April 2004; accepted 8 April 2004
Abstract—Fe-exchanged montmorillonite K10 catalyzes a highly efficient reaction between sterically and electronically diverse
sulfonamides and carboxylic acid anhydrides to furnish N-acylsulfonamides in excellent yield and high selectivity. The catalyst can
also be reused several times.
Ó 2004Elsevier Ltd. All rights reserved.
In drug synthesis, the N-acyl sulfonamide moiety has
emerged as an important feature for biological activity.
Several recently developed drugs, including therapeutic
agents for Alzheimer’s disease,1 inhibitors for tRNA
synthetase as antibacterial agents2 and prostaglandin
Fla sulfonamides for the potential treatment of osteo-
porosis,3 incorporate this moiety. In addition, N-acyl-
N-(2,3,4,5,6-pentafluorophenyl)methane sulfonamides
function as chemoselective N-acylating reagents.4
In recent years, the use of solid acidic catalysts, such as
clays and zeolites, has received considerable attention in
different areas of organic synthesis, because of their
environmental compatibility, reusability, greater selec-
tivity, operational simplicity, nontoxicity, noncorro-
siveness, low cost and ease of isolation. In particular, clay
catalysts make a reaction convenient, more economic
and environmentally benign. They act as both Brønsted
and Lewis acids in their natural and ion-exchanged for-
ms.8 We have recently reported the high activity of
Fe-exchanged montmorillonite clays for the Friedel–
Crafts benzylation of arenes with benzyl chlorides,9a;b;c
the Beckmann rearrangement9d and nitrile formation.9e
The majority of reports describe the preparation of the
N-acyl derivatives using basic reaction media. For in-
stance, the target compounds have been obtained by
coupling sulfonamides with acid chlorides or anhydrides
in the presence of trialkylamines or pyridine,4;5 or alkali
hydroxides.6 Another approach utilizes carboxylic acids
along with coupling agents like EDC, DCC or carbonyl
diimidazole,2;3 the by-product of which must subse-
quently be removed from the reaction mixture. Moris-
awa et al. has used concd H2SO4 in the carboxylic acid
anhydride itself taken as a solvent; whereas Martin et al.
has used concd H2SO4 in acetonitrile.7
The present paper describes a selective and highly effi-
cient procedure for the synthesis of N-acyl sulfonamides
using an inexpensive and reusable Fe-exchanged mont-
morillonite K10 catalyst (K10-FeO) (Scheme 1).
O
O
O
O
K10-FeO
CH3CN, 60 ˚C
R'
R
S
N
H
R
SO2NH2
+
R'
R'
O
O
R = CH3, C6H5, p-CH3C6H4, p-MeOC6H4, p-ClC6H4
Keywords: Fe-exchanged montmorillonite; Sulfonamides; Carboxylic
acid anhydrides.
R' = CH3, C6H5, CF3
* Corresponding author. Tel.: +91-22-24145616; fax: +91-22-241456-
14; e-mail: samantsd@udct.org
Scheme 1. N-acylation of sulfonamides with carboxylic acid anhy-
drides.
0040-4039/$ - see front matter Ó 2004Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.04.077

4806
D. U. Singh et al. / Tetrahedron Letters 45 (2004) 4805–4807
Table 1. N-Acylation of benzenesulfonamide with acetic anhydride in
different solvents using K10-FeO catalyst
The catalyst was prepared by treating Mont. K10 clay
with anhyd FeCl3 in acetonitrile solution as described
earlier.9a The catalyst was activated at 120 °C for 5 h
prior to use.
Entry
Solvent
Time (min)
Yields (%)a
1
2
3
Acetonitrile
Ethyl acetate
Tetrahydrofuran
15
30
45
92
88
94
The reaction of benzenesulfonamide with acetic anhy-
dride was carried out in different solvents in the presence
of K10-FeO (Table 1). Based on this, acetonitrile was
selected as the solvent for further study. These results
can be attributed to the ability of the solvent to stabilize
the acylium intermediate.7 The reaction was carried out
in CH3CN in the presence of different Fe-based catalysts
viz. K10-FeO, K10-FeA,9a K10-FePLS,9c Fe-PILC10
and also K10. K10-FeO was superior to all the other Fe-
based heterogeneous catalysts tested. It should be noted
4Chloroform 5
a Isolated yield.
4
90
that a blank reaction without any catalyst gave no
product even after 5 h under identical conditions. Thus,
it was observed that K10-FeO was the best catalyst for
the reaction. Using this catalyst, different sulfonamides,
primary as well as secondary were reacted with three
Table 2. N-Acylation of arene sulfonamides with different acid anhydrides in acetonitrile in the presence of K10-FeOa
Entry
Sulfonamide 1
Carboxylic acid anhydride 2
N-Acylsulfonamideb
3
Time (min)
Yieldc (%)
92
O
O
O
O
O
O
O
O
O
a
15
S
N
SO2NH2
O
O
O
H
O
O
b
c
15
15
5
95
91
98
82
S
SO2NH2
N
H
O
MeO
Cl
MeO
O
O
O
O
O
S
O
O
O
SO2NH2
N
H
O
S
Cl
O
O
d
e
SO2NH2
N
O
H
O
O
Me
O
MeSO2NH2
S
15
N
H
O
O
O
O
O
f
15
92
74
S
N
O
SO2NHMe
O
Me
O
O
O
O
S
g
120
O
O
N
H
SO2NH2
O
O
O
O
h
S
120
72
N
H
SO2NH2
O
MeO
Cl
O
O
O
O
MeO
O
O
i
j
120
120
67
78
O
O
S
N
SO2NH2
H
O
O
Cl
O
S
N
SO2NH2
O
O
H
O
O
O
O
O
Me
O
S
k
l
MeSO2NH2
120
120
30
62
––
62
O
O
N
H
No reaction
SO2NHMe
O
O
O
O
m
S
F3C
O
CF3
CF3
SO2NH2
N
CF3
O
O
H
Cl
Cl
O
O
O
n
30
66
S
F3C
O
N
CF3
SO2NH2
O
H
a Sulfonamide: 5 mmol; carboxylic acid anhydride: 5 mmol; catalyst: 0.5 g; CH3CN: 5 mL.
b All products were characterized by 1H NMR and IR spectroscopy.
c Isolated and unoptimized yield.

D. U. Singh et al. / Tetrahedron Letters 45 (2004) 4805–4807
4807
8. (a) Balogh, M.; Laszlo, P. Organic Chemistry using Clays;
Springer: Berlin, 1993, and references cited therein; (b)
Cornelis, A.; Laszlo, P. Synlett 1994, 155–161.
anhydrides viz. acetic anhydride, benzoic anhydride and
trifluoroacetic anhydride (Table 2).11;12 Acetic anhydride
was found to be more reactive than trifluoroacetic
anhydride and benzoic anhydride. The reactions pro-
ceeded smoothly with acetic anhydride, whereas the
reactions with benzoic anhydride took longer times. The
reaction of N-methyl-p-toluenesulfonamide with benzoic
anhydride (Table 2, entry l) did not proceed even after
2 h. This may be due to unfavourable steric and elec-
tronic effects of both the sulfonamide and benzoic
anhydride.
9. (a) Pai, S. G.; Bajpai, A. R.; Deshpande, A. B.; Samant,
S. D. J. Mol. Catal. A: Chem. 2000, 156, 233–243; (b) Pai,
S. G.; Bajpai, A. R.; Deshpande, A. B.; Samant, S. D.
Synth. Commun. 1997, 27, 2267–2273; (c) Singh, D. U.;
Samant, S. D. J. Mol. Catal. A: Chem., in press; (d) Pai,
S. G.; Bajpai, A. R.; Deshpande, A. B.; Samant, S. D.
Synth. Commun. 1997, 27, 379–384; (e) Bajpai, A. R.;
Deshpande, A. B.; Samant, S. D. Synth. Commun. 2000,
30, 2785–2791.
10. Fe-pillared bentonite clay (Fe-PILC) was prepared as
reported in Rightor, E. G.; Tzou, M. S.; Pinnavaia, T. J. J.
Catal. 1991, 130, 29–40.
Recyclability of the catalyst, K10-FeO, was also studied.
After each cycle the used catalyst was filtered and acti-
vated at 120 °C before using for the next cycle. The
activity of the catalyst was unaffected even after five
cycles.
11. Typical experimental procedure: A mixture of benzenesulfon-
amide 1a (5 mmol), acetic anhydride 2a (5 mmol) and
K10-FeO (0.5 g) in acetonitrile (5 mL) was stirred at 60 °C
for an appropriate time (Table 2). After complete conver-
sion, as indicated by TLC, the catalyst was filtered off and
water (10–15 mL) was added dropwise to precipitate the
product. The resultant mixture was stirred for 10–15 min.
The solid was filtered-off and purified by column chroma-
tography on silica gel (Merck, 60–120 mesh, EtOAc–
hexane, 3:7) to afford the pure product 3a.
In summary, we have demonstrated that K10-FeO is a
superior heterogeneous acidic catalyst for the N-acyl-
ation of primary and secondary sulfonamides with car-
boxylic anhydrides. The procedure has the advantages
of mild reaction conditions, high yields of products,
cleaner reactions with greater selectivity, short reaction
times, operational simplicity and recyclability, which
makes it useful and attractive for the synthesis of N-
acylated sulfonamide derivatives.
12. All the new products obtained in this study were charac-
1
terized by H NMR and IR.
N-Acetyl benzenesulfonamide 3a: Solid: mp 122–124 °C, IR
(KBr): 3127, 2915, 1704, 1472, 1356, 1245, 1169, 861 cmꢀ1
,
1H NMR (300 MHz, CDCl3): d ¼ 2:08 (s, 3H), 7.54(t,
J ¼ 7:2 Hz, 2H), 7.66 (t, J ¼ 6 Hz, 1H), 8.06 (d, J ¼ 6 Hz,
2H), 8.95 (br s, 1H, NH). Anal. Calcd for C8H9NSO3: C,
48.23; H, 4.55; N, 7.03; S, 16.09. Found: C, 48.35; H, 4.57;
N, 7.10; S, 16.01.
Acknowledgements
N-Acetyl-p-toluenesulfonamide 3b: Solid: mp 138–140 °C,
IR (KBr): 3264, 1726, 1504, 1445, 1337, 1269, 1160,
1026 cmꢀ1, 1H NMR (300 MHz, CDCl3): d ¼ 2:07 (s, 3H),
2.45 (s, 3H), 7.35 (d, J ¼ 7:8 Hz, 2H), 7.94(d, J ¼ 8:4Hz,
2H), 8.2 (br s, 1H, NH). Anal. Calcd for C9H11NSO3: C,
50.69; H, 5.20; N, 6.57; S, 15.04. Found: C, 50.51; H, 5.23;
N, 6.66; S, 14.98.
D.U.S. and P.R.S. are grateful to G. D. Gokhale
Charitable Trust for fellowships.
References and notes
N-Acetyl-p-chlorobenzenesulfonamide 3d: Solid: mp 192–
194 °C, IR (KBr): 3291, 3069, 1701, 1459, 1426,
1341, 1183, 1064 cmꢀ1 1H NMR (300 MHz, CDCl3):
,
1. Hasegawa, T.; Yamamoto, H. Bull. Chem. Soc. Jpn. 2000,
73, 423–428.
2. Banwell, M. G.; Crasto, C. F.; Easton, C. J.; Forrest,
A. K.; Karoli, T.; March, D. R.; Mensah, L.; Nairn, M.
R.; O’Hanlon, P. J.; Oldham, M. D.; Yue, W. Bioorg.
Med. Chem. Lett. 2000, 10, 2263–2266.
d ¼ 2:07 (s, 3H), 7.54(d,
J ¼ 6:9 Hz, 2H), 8.0 (d,
J ¼ 8:7 Hz, 2H), 8.2 (br s, 1H, NH). Anal. Calcd for
C8H8ClNSO3: C, 41.12; H, 3.45; Cl, 15.17; N, 5.99;
S, 13.72. Found: C, 41.24; H, 3.47; Cl, 15.23; N, 6.1; S,
13.67.
3. Wang, Y.; Soper, D. L.; Dirr, M. J.; Delong, M. A.; De,
B.; Wos, J. A. Chem. Pharm. Bull. 2000, 48, 1332–
1339.
4. Kondo, K.; Sekimoto, E.; Nakao, J.; Murakami, Y.
Tetrahedron 2000, 56, 5843–5856.
5. Kondo, K.; Sekimoto, E.; Miki, K.; Murakami, Y.
J. Chem. Soc., Perkin Trans. 1 1998, 2973–2974.
6. (a) Ishizuka, N.; Matsumura, K. I.; Hayashi, K.; Sakai,
K.; Yamamori, T. Synthesis 2000, 6, 784–788; (b)
Ishizuka, N.; Matsumura, K. Japanese Patent
JP-10045705, 1998; (c) Inoe, T.; Myahara, O.; Takahashi,
A.; Nakamura, Y. Japanese Patent JP-08198840, 1996.
7. (a) Morisowa, Y.; Kataoka, M.; Negahori, H.; Sakamoto,
T.; Kitano, N.; Kusano, K. J. Med. Chem. 1980, 23, 1376–
1380; (b) Martin, M. T.; Roschangar, F.; Eaddy, J. F.
Tetrahedron Lett. 2003, 44, 5461–5463.
N-Benzoyl-p-toluenesulfonamide 3h: Solid: mp 147–149 °C,
IR (KBr): 3121, 2905, 1699, 1474, 1429, 1357, 1239, 1166,
1
1090, 860 cmꢀ1, H NMR (300 MHz, CDCl3): d ¼ 2:44 (s,
3H), 7.35 (d, J ¼ 8:4Hz, 2H), 7.43 (t, J ¼ 7:8 Hz, 2H),
7.55 (t, J ¼ 7:5 Hz, 1H), 7.8 (d, J ¼ 7:2 Hz, 2H), 8.04(d,
J ¼ 6:9 Hz, 2H), 9.22 (br s, 1H, NH). Anal. Calcd for
C14H13NSO3: C, 61.08; H, 4.76; N, 5.09; S, 11.65. Found:
C, 60.86; H, 4.77; N, 5.14; S, 11.58.
N-Benzoyl-p-chlorobenzenesulfonamide 3j: Solid: mp 185–
186 °C, IR (KBr): 3246, 2939, 1780, 1475, 1370, 1308,
1237, 1166, 892 cmꢀ1
,
1H NMR (300 MHz, CDCl3):
d ¼ 7:5 (m, 5H), 7.78 (d, J ¼ 7:2 Hz, 2H), 8.1 (d,
J ¼ 7:8 Hz, 2H), 8.94(br s, 1H, NH). Anal. Calcd for
C13H10ClNSO3: C, 52.8; H, 3.41; Cl, 11.99; N, 4.74; S,
10.84. Found: C, 52.62; H, 3.42; Cl, 12.13; N, 4.78; S,
10.94.