Zinc oxide as a new, highly efficient, green, and reusable catalyst for microwave-assisted Michael addition of sulfonamides to α,β- unsaturated esters in ionic liquids

Article abstract of DOI:10.1139/V07-050

A simple, clean, and efficient procedure for the green synthesis of some N-alkyl derivatives of sulfonamides is described. Microwave-assisted Michael addition of sulfonamides to α,β-unsaturated esters, in the presence of catalytic amount of zinc oxide (Zn

Full text of DOI:10.1139/V07-050

438
Zinc oxide as a new, highly efficient, green, and
reusable catalyst for microwave-assisted Michael
addition of sulfonamides to ␣,␤-unsaturated esters
in ionic liquids
Abdolkarim Zare, Alireza Hasaninejad, Ahmad Reza Moosavi Zare,
Abolfath Parhami, Hashem Sharghi, and Ali Khalafi-Nezhad
Abstract: A simple, clean, and efficient procedure for the green synthesis of some N-alkyl derivatives of sulfonamides
is described. Microwave-assisted Michael addition of sulfonamides to α,β-unsaturated esters, in the presence of cata-
lytic amount of zinc oxide (ZnO) in 1-butyl-3-methylimidazolium bromide ([bmim]Br), affords the title compounds in
high yields and short reaction times.
Key words: zinc oxide, green chemistry, microwave, Michael addition, sulfonamide, ionic liquid.
Résumé : On décrit une méthode simple, propre et efficace pour la synthèse verte de quelques dérivés N-alkyles des
sulfonamides. L’addition de Michael assistée par micro-ondes de sulfonamides sur des esters α,β-insaturés, en présence
d’une quantité catalytique d’oxyde de zinc (ZnO) dans le bromure de 1-butyl-3-méthylimidazolium ([bmim]Br) conduit
à la formation des produits mentionnés dans le titre, avec des rendements élevés et de courts temps de réaction.
Mots-clés : oxyde de zinc, chimie verte, micro-onde, addition de Michael, sulfonamide, liquide ionique.
[Traduit par la Rédaction] Zare et al. 444
Introduction
uids as efficient reaction media for useful organic transfor-
mations at room temperature.
Currently, ionic liquids are the subject of considerable in-
terest as benign reaction media in organic synthesis because
of their unique properties, such as non-volatility, non-
flammability, recyclability, and ability to dissolve a wide
range of materials (1). During the past decade, a variety of
ionic liquids have been demonstrated as efficient and practi-
cal alternatives to organic solvents for many important or-
ganic transformations (1). Catalytic activity has been also
reported for these green solvents (2). Together with the sub-
stitution of common molecular solvents, non-conventional
activation methods, mainly microwave irradiation (MWI),
have emerged as powerful techniques to reduce reaction
times and to enhance reaction rates (3). As part of our drive
to avoid the use of volatile organic solvents in reactions (4),
we have initiated a program to explore the use of ionic liq-
N-Alkyl derivatives of sulfonamides are important be-
cause they have various biological activities, including their
antidepressant, psychostimulant, analgesic, anti-ulcer, anti-
emetic, and anti-inflammatory properties (5). These com-
pounds can be prepared via aza-conjugate addition of
sulfonamides to α,β-unsaturated compounds (6). Michael re-
action of sulfonamides with α,β-unsaturated esters also af-
fords protected β-amino acids. This class of compounds (β-
amino acids) are essential components in many bioactive
compounds and drugs scaffolds, such as β-peptides (7),
imeriamine (hypoglycemic and antiketogenic agent, Fig. 1)
(8), vitamin B3 (Fig. 1) (9), cryptophycin (antitumor) (10),
and TAN-1057 A (antibiotic) (11). Indeed, to the best of our
knowledge, there are only a few reports of Michael addition
of sulfonamides. Reitz et. al have used alumina to carry out
this reaction (6). However, in their report, the reaction times
are long, and the yields are moderate. Moreover, they ap-
plied more reactive α,β-unsaturated ketones.
In aza-conjugate reactions, the nucleophilic nitrogen is
usually among the powerful nucleophiles, such as amines
(12), which, if used in the reaction, can lead to side prod-
ucts, e.g., amides via nucleophilic attack of amine to car-
bonyl group of α,β-unsaturated esters (12a). Furthermore,
1,2- and 1,4-condensation of a β-amino residue to α,β-
unsaturated esters caused polymerization or tar formation
(12a). Moreover, some procedures often require a large ex-
cess of reagents (12b). Therefore, in this context, using
sulfonamides instead of amines in Michael reaction with
Received 6 March 2007. Accepted 9 May 2007. Published on
the NRC Research Press Web site at canjchem.nrc.ca on
12 June 2007.
A. Zare.1 Department of Chemistry, Payam Noor University
of Bushehr, Bushehr 1698, Iran.
A. Hasaninejad.2 Department of Chemistry, Faculty of
Sciences, Persian Gulf University, Bushehr 75169, Iran.
A.R. Moosavi Zare, A. Parhami, H. Sharghi, and
A. Khalafi-Nezhad. Department of Chemistry, College of
Sciences, Shiraz University, Shiraz 71454, Iran.
1Corresponding author (e-mail: abdolkarimzare@yahoo.com).
2Corresponding author (e-mail: ahassaninejad@yahoo.com).
Can. J. Chem. 85: 438–444 (2007)
doi:10.1139/V07-050
© 2007 NRC Canada

Zare et al.
439
Scheme 1. Michael addition of benzenesulfonamide to n-butyl acrylate.
Fig. 1. The structures of imeriamine and vitamin B3.
Table 1. The effect of different basic catalysts on Michael addi-
tion of benzenesulfonamide (2 mmol) with n-butyl acrylate
(2.2 mmol) in [bmim]Br (2 g) under MW conditions (300 W,
max. 110 °C).
Yielda (%)
Time
(min)
N-Alkylated
product
N,N-Dialkylated
product
Catalyst
α,β-unsaturated esters seems to be more favorable, since
lower nucleophilicity of nitrogen leads to less side reactions.
Recently, mineral oxides have proved to be useful to
chemists both in the laboratory and in the industry because
of the good activation of adsorbed compounds, reaction rate
enhancement, selectivity, easier workup, recyclability of the
supports, and the eco-friendly reaction conditions (13, 14).
Zinc oxide (ZnO) is certainly one of the most interesting of
these oxides because it has surface properties that can
accomodate rich organic reactions (14). Zinc oxide is an in-
expensive, moisture stable, reusable, commercially available,
and environmentally benign catalyst. This catalyst has been
used in several transformations, such as Beckmann rear-
rangement (14a), Friedel–Crafts acylation (14b), benzylic
oxidation (14c), conversion of oximes to nitriles (14d), syn-
thesis of cyclic ureas (14e), and acylation of alcohols and
amines (14f, 14g).
6
8
9
13
22
29
8
ZnO (10%)
ZnO (15%)
ZnO (20%)
ZnO (30%)
ZnO (50%)
ZnO (100%)
K2CO3 (20%)
8
8
5
5
5
5
6
67
75
86
77
63
50
57
Cs2CO3 (20%)
5
68
13
t-BuOK (20%)
Basic Al2O3 (20%)
5
7
67
58
11
9
NBu3 (20%)
8
8
22
17
<3
<3
DABCO (20%)
aIsolated yield.
ZnO was investigated (Table 1). The optimum amount of
ZnO was found to be 20 mol%.
Herein, we report a clean, facile, and rapid method for
Michael addition of sulfonamides to α,β-unsaturated esters
in the presence of catalytic amount of zinc oxide in
[bmim]Br under MWI (Scheme 1). In this method, N,N-
dialkyl sulfonamides formed together with the N-alkylated
products in very low yields.
To select the appropriate MW power, conjugate addition
of benzenesulfonamide to n-butyl acrylate was examined at
different MW powers (100–600 W), with controlled temper-
ature (max. 110 °C), in the presence of ZnO, and in
[bmim]Br. The best results were observed at 300 W.
To compare the efficiency of the ionic liquid with that of
the conventional solvents, the model reaction was examined
in various conventional solvents. Thus, a mixture of
benzenesulfonamide (2 mmol), ZnO (0.4 mmol), and n-butyl
acrylate (2.2 mmol) was irradiated in a MW oven (300 W,
max. 110 °C) in different solvents (5 mL) (Table 2). Clearly,
conventional solvents exhibited lower selectivities and lon-
ger reaction times compared with [bmim]Br. Therefore, the
ionic-liquid-accelerated method is more efficient.
The capability and efficiency of MW heating, compared
with conventional heating, on Michael reaction was also in-
vestigated. For this purpose, compounds 1b and 2b as well
as 1g and 2g were prepared via Michael reaction between
benzenesulfonamide and α,β-unsaturated esters in the pres-
ence of ZnO in [bmim]Br under thermal conditions (110 °C)
(Table 3). As Table 3 demonstrates, MW conditions gave
better results compared with thermal conditions. This can be
attributed to the efficient performance of the reactions with
more polar transition state relative to the ground state un-
der MWI (3a–3c).
Results and discussion
To optimize reaction conditions, Michael addition of
benzenesulfonamide to n-butyl acrylate was studied as a
model reaction to provide compounds 1b and 2b
(Scheme 1). First, the efficiency of several ionic liquids, in-
cluding [bmim]Br, [bmim]Cl, [bmim]BF4, and [bmim]PF6,
was investigated in the presence of ZnO (20 mol%) un-
der MWI (300 W, max. 110 °C). Interestingly, all examined
ionic liquids afforded almost similar yields and reaction
times. However, [bmim]Br was applied as solvent for all re-
actions because the preparation of this ionic liquid was easy,
compared with other ionic liquids.
In another study, the influence of various inorganic and
organic basic catalysts on the model reaction was studied.
The results are summarized in Table 1. Clearly, higher selec-
tivity in shorter reaction time was attained when ZnO was
used. Therefore, ZnO was the catalyst of choice in all reac-
tions. Moreover, the effect of using different amounts of
© 2007 NRC Canada

440
Can. J. Chem. Vol. 85, 2007
Table 2. Comparative Michael addition of benzenesulfonamide
(2 mmol) to n-butyl acrylate (2.2 mmol) in the presence of ZnO
(0.4 mmol) in conventional solvents (5 mL) vs. [bmim]Br (2 g)
under MWI (300 W, max. 110 °C).
mides with α,β-unsaturated esters under MWI. The promis-
ing points for the presented methodology are high conver-
sion, ease of handling and low cost of the catalyst, cleaner
reaction profile, and short reaction times, which makes it a
useful and attractive process for the rapid synthesis of N-
alkyl sulfonamides as biologically interesting compounds.
Yielda (%)
Time
(min)
N-Alkylated
product
N,N-Dialkylated
product
Solvent
Experimental
8
12
10
9
11
9
—
DMSO
DMF
HMPTA
o-Xylene
[bmim]Br
25
20
20
25
25
5
37
68
63
50
44
86
All chemicals were purchased from Merck or Fluka chem-
ical companies. The progress of the reactions was followed
with TLC using silica gel SILG/UV 254 plates. Silica gel
60, 0.063–0.200 mm (70–230 mesh ASTM) was used for
column chromatography. All reactions were carried out us-
ing CEM MARS 5TM MW oven. IR spectra were run on a
Shimadzu FTIR-8300 spectrophotometer; νmax values are re-
aIsolated yield.
1
ported in cm–1. The H NMR (250 MHz) and 13C NMR
Table 3. Comparative synthesis of compounds 1b and 2b as well
as 1g and 2g using conventional heating (∆, 110 °C) vs. the MW
method (MW, 300 W, max. 110 °C).
(62.5 MHz) were run on a Bruker AVANCE DPX-250
FTNMR spectrometer. Mass spectra were recorded on a
Shimadzu GC MS-QP 1000 EX apparatus. Microanalyses
were performed on a PerkinElmer 240-B microanalyzer.
Melting points were recorded on a Büchi B-545 apparatus in
open capillary tubes and are uncorrected.
Compound
Time (min)
Yielda (%)
∆
MW
5
∆
MW
1b
2b
1g
2g
240
65
16
53
9
86
9
78
6
General procedure for the preparation of compounds
1b and 2b
300
9
To a mixture of benzenesulfonamide (0.31 g, 2 mmol),
well-ground ZnO (0.033 g, 0.4 mmol), and n-butyl acrylate
(0.28 g, 2.2 mmol) in a MW vessel was added [bmim]Br
(2 g) and mixed carefully. The resulting mixture was irradi-
ated in a MW oven at 300 W for 5 min. The oven was pro-
grammed to give a maximum internal temperature of
110 °C. Afterward, the reaction mixture was cooled to room
temperature and was extracted with Et2O (3 × 25 mL). The
organic extracts were then combined. After the removal of
the solvent, the crude product was purified by column chro-
matography on silica gel with EtOAc–n-hexane (1:3) to give
1b and 2b as colorless oils. After isolating the products and
evaporating the remainder Et2O in ionic liquid, the ionic liq-
uid containing the catalyst ZnO ([bmim]Br–ZnO) was used
for the next run under identical reaction conditions.
aIsolated yield.
After optimizing the reaction conditions, Michael addition
of sulfonamides was examined with structurally diverse α,β-
unsaturated esters. The results are depicted in Table 4. The
reactions proceeded efficiently, and the desired Michael ad-
ducts were obtained in high yields.
To study the structural influence of the alkoxy groups
(–OR) of α,β-unsaturated esters (Michael acceptors) on the
reaction, we have investigated the reaction of benzenesul-
fonamide with esters containing sterically hindered alkoxy
groups. The results showed that the bulkiness of the alkoxy
group had no significant effect on the yields, the selectivi-
ties, and the reaction times (Table 4, entries 1–6). The struc-
tural effect of α,β-unsaturated esters on Michael-addition
reaction was also studied. Lower yields of the products and
longer reaction times were observed when benzenesulfon-
amide was added to sterically hindered α,β-unsaturated es-
ters (ethyl methacrylate and ethyl crotonate) (Table 4, entries
7 and 8). However, in these cases, the selectivity increased.
Interestingly, the reaction of benzenesulfonamide as well as
naphthalene-2-sulfonamide with ethyl crotonate afforded
only the monoalkylated product (Table 4, entries 8 and 10).
When 4-methylbenzenesulfonamide was used instead of
benzenesulfonamide, the yields decreased (Table 4, entries 2
and 9).
Ethyl 3-(phenylsulfonamido)propanoate (1a)
Colorless oil; isolated yield: 0.433 g (84%). IR (neat, cm–1):
3286, 3059, 2975, 1732, 1447, 1329. 1H NMR (CDCl3,
ppm) δ: 1.16 (t, 3H, J = 7.0 Hz, CH3), 2.48 (t, 2H, J =
5.0 Hz, O=CCH2), 3.15 (t, 2H, J = 5.0 Hz, O=CCH2CH2),
4.02 (q, 2H, J = 7.0 Hz, OCH2), 5.56 (s, 1H, NH, exchange-
able with D2O), 7.42–7.52 (complex, 3H, H3–H5 of the aro-
matic ring), 7.80 (m, 2H, H2 and H6 of the aromatic ring).
13C NMR (CDCl3) δ: 14.0, 34.1, 38.7, 60.7, 127.0, 128.7,
132.6, 138.8, 171.7. MS m/z: 257 [M+]. Anal. calcd. for
C11H15NO4S: C 51.35, H 5.88, N 5.44; found: C 51.52, H
6.01, N 5.30.
The interesting behavior of [bmim]Br–ZnO system lies in
the fact that it can be re-used after simple washing with
Et2O, thus rendering the process more economic. The yields
of compounds 1b and 2b (model compounds) in the second,
third, fourth, and fifth uses of the [bmim]Br/ZnO were al-
most as high as in the first use.
Compound 2a
Colorless oil; isolated yield: 0.072 g (10%). IR (neat, cm–1):
1
3028, 2984, 1733, 1447, 1317. H NMR (CDCl3, ppm) δ:
1.22 (t, 6H, J = 7.1 Hz, 2CH3), 2.59 (t, 4H, J = 5.0 Hz,
2O=CCH2), 3.45 (t, 4H, J = 5.0 Hz, 2O=CCH2CH2), 4.08 (q,
4H, J = 7.1 Hz, 2OCH2), 7.46–7.57 (complex, 3H, H3–H5 of
In conclusion, we have introduced a highly efficient cata-
lyst for ionic-liquid-accelerated Michael addition of sulfona-
© 2007 NRC Canada

Zare et al.
441
Table 4. Ionic-liquid-accelerated Michael addition of sulfonamides to α,β-unsaturated esters using ZnO under MWI
(300 W, 110 °C).
aIsolated yield.
bIn this reaction, the molar ratio of α,β-unsaturated ester/sulfonamide was 1.3:1.
cIn this case, only monosubstituted Michael adduct was produced.
the aromatic ring), 7.87 (m, 2H, H2 and H6 of the aromatic
ring). 13C NMR (CDCl3) δ: 13.9, 32.8, 44.7, 60.4, 127.2,
129.1, 132.6, 138.9, 170.9. MS m/z: 357 [M+]. Anal. calcd.
for C16H23NO6S: C 53.77, H 6.49, N 3.92; found: C 53.98,
H 6.33, N 4.08.
4.03 (t, 2H, J = 7.0 Hz, OCH2), 5.68 (s, 1H, NH,
exchangeable with D2O), 7.48–7.57 (complex, 3H, H3–H5 of
the aromatic ring), 7.79 (m, 2H, H2 and H6 of the aromatic
ring). 13C NMR (CDCl3) δ: 13.5, 18.9, 30.4, 34.1, 38.7,
64.6, 126.8, 129.0, 132.5, 139.9, 172.7. MS m/z: 285 [M+].
Anal. calcd. for C13H19NO4S: C 54.72, H 6.71, N 4.91;
found: C 54.48, H 6.92, N 5.06.
Butyl 3-(phenylsulfonamido)propanoate (1b)
Colorless oil; isolated yield: 0.492 g (86%). IR (neat, cm–1):
3271, 3048, 2960, 1733, 1447, 1330. 1H NMR (CDCl3,
ppm) δ: 0.90 (t, 3H, J = 6.5 Hz, CH3), 1.34 (m, 2H,
CH3CH2), 1.56 (m, 2H, CH3CH2CH2), 2.51 (t, 2H, J =
5.0 Hz, O=CCH2), 3.19 (t, 2H, J = 5.0 Hz, O=CCH2CH2),
Compound 2b
Colorless oil; isolated yield: 0.075 g (9%). IR (neat, cm–1):
1
3036, 2966, 1732, 1447, 1317. H NMR (CDCl3, ppm) δ:
0.92 (t, 6H, J = 6.5 Hz, 2CH3), 1.33 (m, 4H, 2CH3CH2),
© 2007 NRC Canada

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Can. J. Chem. Vol. 85, 2007
1.56 (m, 4H, 2CH3CH2CH2), 2.63 (t, 4H, J = 5.1 Hz,
2O=CCH2), 3.45 (t, 4H, J = 5.1 Hz, 2O=CCH2CH2), 4.06 (t,
4H, J = 6.9 Hz, 2OCH2), 7.51–7.60 (complex, 3H, H3–H5 of
the aromatic ring), 7.82 (m, 2H, H2 and H6 of the aromatic
ring). 13C NMR (CDCl3) δ: 13.5, 18.9, 30.5, 34.2, 44.4,
64.2, 126.9, 129.0, 132.4, 138.9, 171.1. MS m/z: 413 [M+].
Anal. calcd. for C20H31NO6S: C 58.09, H 7.56, N 3.39;
found: C 58.20, H 7.69, N 3.25.
65.5, 126.2, 127.7, 128.1, 128.9, 129.5, 131.8, 134.4, 137.8,
171.4. MS m/z: 404 [M+ – C6H5], 374 [M+ – C7H7O], 340
[M+ – C6H5SO2). Anal. calcd. for C26H27NO6S: C 64.85, H
5.65, N 2.91; found: C 65.04, H 5.48, N 2.80.
Phenethyl 3-(phenylsulfonamido)propanoate (1e)
Pale yellow oil; isolated yield: 0.564 g (85%). IR
1
(neat, cm–1): 3285, 3063, 2957, 1732, 1447, 1329. H NMR
(CDCl3, ppm) δ: 2.48 (t, 2H, J = 5.2, O=CCH2), 2.88 (t, 2H,
J = 6.8 Hz, ArCH2), 3.14 (t, 2H, J = 5.2 Hz, O=CCH2CH2),
4.24 (t, 2H, J = 6.8 Hz, OCH2), 5.43 (s, 1H, NH), 7.15–7.28
(complex, 5H, H1–H5 of the alkoxy groups of the aromatic
ring), 7.47–7.52 (complex, 3H, H3–H5 of the aromatic ring
of sulfonamide), 7.84 (m, 2H, H2 and H6 of the aromatic
ring of sulfonamide). 13C NMR (CDCl3) δ: 34.1, 34.9, 38.7,
65.2, 126.6, 126.9, 128.5, 128.8, 129.1, 132.7, 137.5, 139.9,
171.7. MS m/z: 333 [M+]. Anal. calcd. for C17H19NO4S: C
61.24, H 5.74, N 4.20; found: C 60.97, H 5.89, N 4.29.
Hexyl 3-(phenylsulfonamido)propanoate (1c)
Colorless oil; isolated yield: 0.532 g (85%). IR (neat, cm–1):
3275, 3044, 2967, 1732, 1447, 1328. 1H NMR (CDCl3,
ppm) δ: 0.90 (t, 3H, J = 6.7 Hz, CH3), 1.28–1.34 (complex,
6H, CH3CH2, CH3CH2CH2 and CH3(CH2)2CH2), 1.57 (m,
2H, CH3(CH2)3CH2), 2.56 (t, 2H, J = 5.1 Hz, O=CCH2),
3.16 (t, 2H, J = 5.1 Hz, O=CCH2CH2), 4.09 (t, 2H, J =
6.9 Hz, OCH2), 5.63 (s, 1H, NH), 7.41–7.48 (complex, 3H,
H3–H5 of the aromatic ring), 7.78 (m, 2H, H2 and H6 of the
aromatic ring). 13C NMR (CDCl3) δ: 13.5, 22.5, 25.5, 27.9,
30.6, 34.1, 38.5, 64.9, 126.5, 128.7, 132.2, 139.5, 171.8. MS
m/z: 313 [M+]. Anal. calcd. for C15H23NO4S: C 57.48, H
7.40, N 4.47; found: C 57.26, H 7.58, N 4.62.
Compound 2e
Pale yellow oil; isolated yield: 0.083 g (8%). IR
(neat, cm–1): 3045, 2942, 1733, 1447, 1331. 1H NMR
(CDCl3, ppm) δ: 2.51 (t, 4H, J = 5.2 Hz, 2O=CCH2), 2.82 (t,
4H, J = 6.9 Hz, 2ArCH2), 3.30 (t, 4H, J = 5.2 Hz,
2O=CCH2CH2), 4.19 (t, 4H, J = 6.9 Hz, 2OCH2), 7.10–7.19
(complex, 10H, H1–H5 of the alkoxy groups of the aromatic
ring), 7.42–7.45 (complex, 3H, H3–H5 of the aromatic ring
of sulfonamide), 7.78 (m, 2H, H2 and H6 of the aromatic
ring of sulfonamide). 13C NMR (CDCl3) δ: 34.3, 34.9, 44.9,
65.2, 126.6, 126.7, 126.9, 128.6, 128.8, 129.2, 132.8, 137.5,
171.0. MS m/z: 432 [M+ – C6H5], 388 [M+ – C8H9O], 368
[M+ – C6H5SO2]. Anal. calcd. for C28H31NO6S: C 65.99, H
6.13, N 2.75; found: C 65.87, H 6.26, N 2.89.
Compound 2c
Colorless oil; isolated yield: 0.084 g (9%). IR (neat, cm–1):
1
3031, 2974, 1733, 1447, 1316. H NMR (CDCl3, ppm) δ:
0.89 (t, 6H, J = 6.6 Hz, 2CH3), 1.26–1.32 (complex, 12H,
2CH3CH2, 2CH3CH2CH2 and 2CH3(CH2)2CH2), 1.58 (m,
4H, 2CH3(CH2)3CH2), 2.61 (t, 4H, J = 5.0 Hz, 2O=CCH2),
3.41 (t, 4H, J = 5.0 Hz, 2O=CCH2CH2), 4.05 (t, 4H, J =
6.9 Hz, 2OCH2), 7.43–7.50 (complex, 3H, H3–H5 of the aro-
matic ring), 7.74 (m, 2H, H2 and H6 of the aromatic ring).
13C NMR (CDCl3) δ: 13.8, 22.3, 25.5, 28.0, 30.4, 33.9, 44.5,
64.4, 126.4, 128.9, 132.1, 139.4, 171.4. MS m/z: 392 [M+ –
C6H5], 368 [M+ – C6H13O), 328 [M+ – C6H5SO2]. Anal.
calcd. for C24H39NO6S: C 61.38, H 8.37, N 2.98; found: C
61.13, H 8.23, N 3.11.
Cinnamyl 3-(phenylsulfonamido)propanoate (1f)
Pale yellow oil; isolated yield: 0.568 g (82%). IR
1
(neat, cm–1): 3287, 3059, 2964, 1732, 1447, 1329. H NMR
(CDCl3, ppm) δ: 2.55 (t, 2H, J = 5.2 Hz, O=CCH2), 3.19 (t,
2H, J = 5.2 Hz, O=CCH2CH2), 4.69 (m, 2H, OCH2), 5.50 (s,
1H, NH), 6.23 (m, 1H, PhCH=CH), 6.63 (d, 1H, J =
15.7 Hz, PhCH), 7.29–7.35 (complex, 5H, H1–H5 of the
alkoxy groups of the aromatic ring), 7.45–7.50 (complex,
3H, H3–H5 of the aromatic ring of sulfonamide), 7.95 (m,
2H, H2 and H6 of the aromatic ring of sulfonamide). 13C
NMR (CDCl3) δ: 34.2, 38.8, 65.8, 122.6, 122.9, 126.6,
126.9, 128.1, 128.6, 129.0, 132.7, 134.6, 139.9, 171.7. MS
m/z: 345 [M+]. Anal. calcd. for C18H19NO4S: C 62.59, H
5.54, N 4.06; found: C 62.82, H 5.39, N 4.21.
Benzyl 3-(phenylsulfonamido)propanoate (1d)
Pale yellow oil; isolated yield: 0.535 g (84%). IR
(neat, cm–1): 3286, 3031, 2954, 1733, 1447, 1328. H NMR
1
(CDCl3, ppm) δ: 2.65 (t, 2H, J = 5.1 Hz, O=CCH2), 3.17 (t,
2H, J = 5.1 Hz, O=CCH2CH2), 5.00 (s, 2H, OCH2), 5.71 (s,
1H, NH), 7.26–7.31 (complex, 5H, H1–H5 of the alkoxy
groups of the aromatic ring), 7.45–7.51 (complex, 3H, H3–
H5 of the aromatic ring of sulfonamide), 7.82 (m, 2H, H2
and H6 of the aromatic ring of sulfonamide). 13C NMR
(CDCl3) δ: 34.2, 38.7, 66.6, 126.9, 128.2, 128.4, 128.6,
129.2, 132.7, 135.4, 139.9, 171.7. MS m/z: 319 [M+]. Anal.
calcd. for C16H17NO4S: C 60.17, H 5.37, N 4.39; found: C
59.94, H 5.56, N 4.26.
Compound 2f
Pale yellow oil; isolated yield: 0.094 g (9%). IR
(neat, cm–1): 3026, 2981, 1732, 1448, 1317. 1H NMR
(CDCl3, ppm) δ: 2.51 (t, 4H, J = 5.1 Hz, 2O=CCH2), 3.41 (t,
4H, J = 5.1 Hz, 2O=CCH2CH2), 4.73 (m, 4H, 2OCH2), 6.15
(m, 2H, 2PhCH=CH), 6.54 (d, 2H, J = 15.7 Hz, 2PhCH),
7.28–7.36 (complex, 10H, H1–H5 of the alkoxy groups of
the aromatic ring), 7.41–7.47 (complex, 3H, H3–H5 of the
aromatic ring of sulfonamide), 7.94 (m, 2H, H2 and H6 of
the aromatic ring of sulfonamide). 13C NMR (CDCl3) δ:
33.8, 43.2, 65.4, 122.4, 123.0, 126.7, 126.9, 127.9, 128.5,
Compound 2d
Pale yellow oil; isolated yield: 0.081 g (8%). IR
(neat, cm–1): 3051, 2965, 1734, 1447, 1316. 1H NMR
(CDCl3, ppm) δ: 2.58 (t, 4H, J = 5.0 Hz, 2O=CCH2), 3.36 (t,
4H, J = 5.0 Hz, 2O=CCH2CH2), 5.00 (s, 4H, 2OCH2), 7.22–
7.25 (complex, 10H, H1–H5 of the alkoxy groups of the aro-
matic ring), 7.39–7.48 (complex, 3H, H3–H5 of the aromatic
ring of sulfonamide), 7.72 (m, 2H, H2 and H6 of the aro-
matic ring of sulfonamide). 13C NMR (CDCl3) δ: 33.3, 43.9,
129.4, 132.4, 134.1, 139.3, 171.5. MS m/z: 400 [M+
–
© 2007 NRC Canada

Zare et al.
443
C9H9O], 392 [M+ – C6H5SO2]. Anal. calcd. for C30H31NO6S:
C 67.52, H 5.86, N 2.62; found: C 67.40, H 5.71, N 2.78.
7.31 (d, 2H, J = 7.9 Hz, H3 and H5 of the aromatic ring),
7.72 (d, 2H, J = 7.9 Hz, H2 and H6 of the aromatic ring). 13
C
NMR (CDCl3) δ: 13.6, 19.0, 21.4, 30.4, 33.9, 45.0, 64.5,
126.9, 129.5, 135.9, 143.5, 172.5. MS m/z: 427 [M+]. Anal.
calcd. for C21H33NO6S: C 58.99, H 7.78, N 3.28; found: C
59.15, H 7.68, N 3.14.
Ethyl 2-methyl-3-(phenylsulfonamido)propanoate (1g)
Pale yellow oil; isolated yield: 0.421 g (78%). IR
1
(neat, cm–1): 3283, 3034, 2966, 1732, 1447, 1328. H NMR
(CDCl3, ppm) δ: 1.17–1.26 (complex, 6H, 2CH3), 2.73 (m,
1H, O=CCH), 3.14–3.20 (complex, 2H, O=CCH(CH3)CH2),
4.12 (q, 2H, J = 7.0 Hz, OCH2), 5.65 (s, 1H, NH), 7.55–7.64
(complex, 3H, H3–H5 of the aromatic ring), 7.93 (m, 2H, H2
and H6 of the aromatic ring). 13C NMR (CDCl3) δ: 14.0,
14.7, 39.6, 45.4, 60.8, 126.8, 129.1, 132.5, 139.9, 174.7. MS
m/z: 271 [M+]. Anal. calcd. for C12H17NO4S: C 53.12, H
6.32, N 5.16; found: C 53.31, H 6.57, N 5.01.
Ethyl 3-(naphthalene-2-sulfonamido)butanoate (1j)
Colorless buff; isolated yield: 0.453
g (70%). IR
(neat, cm–1): 3284, 3051, 2970, 1732, 1447, 1329. H NMR
(CDCl3, ppm) δ: 1.07–1.12 (complex, 6H, 2CH3), 2.31–2.35
(complex, 2H, O=CCH2), 3.67 (m, 1H, O=CCH2CH), 3.99
(q, 2H, J = 7.0 Hz, OCH2), 5.38 (s, 1H, NH), 7.52–7.57
(complex, 4H), 7.79–7.90 (complex, 3H). 13C NMR (CDCl3)
δ: 14.0, 21.1, 40.6, 46.7, 60.7, 122.3, 127.5, 127.7, 127.9,
128.1, 128.3, 128.8, 129.2, 129.5, 132.1, 171.1. MS m/z: 321
[M+]. Anal. calcd. for C16H19NO4S: C 59.79, H 5.96, N
4.36; found: C 59.90, H 6.11, N 4.51.
1
Compound 2g
Pale yellow oil; isolated yield: 0.048 g (6%). IR
(neat, cm–1): 3042, 2982, 1732, 1447, 1316. 1H NMR
(CDCl3, ppm) δ: 1.09–1.19 (complex, 12H, 4CH3), 2.78 (m,
2H, 2O=CCH), 3.22–3.27 (complex, 4H, 2O=CCH(CH3)CH2),
4.03 (q, 4H, J = 7.0 Hz, 2OCH2), 7.44–7.53 (complex, 3H,
H3–H5 of the aromatic ring), 7.75 (m, 2H, H2 and H6 of the
aromatic ring). 13C NMR (CDCl3) δ: 14.1, 15.3, 39.2, 52.4,
60.7, 127.3, 129.1, 132.7, 139.0, 174.7. MS m/z: 385 [M+].
Anal. calcd. for C18H27NO6S: C 56.08, H 7.06, N 3.63;
found: C 55.80, H 7.23, N 3.77.
Acknowledgements
We are grateful to Payam Noor University of Bushehr,
Persian Gulf University, and Shiraz University Research
Councils for the financial support of this work.
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Ethyl 3-(phenylsulfonamido)butanoate (1h)
Pale yellow solid; isolated yield: 0.394 g (73%); mp 60–
62 °C. IR (KBr, cm–1): 3285, 3044, 2953, 1732, 1447, 1329.
1H NMR (CDCl3, ppm) δ: 1.14–1.23 (complex, 6H, 2CH3),
2.38–2.43 (complex, 2H, O=CCH2), 3.68 (m, 1H,
O=CCH2CH), 4.04 (q, 2H, J = 7.1 Hz, OCH2), 5.39 (s, 1H,
NH), 7.49–7.59 (complex, 3H, H3–H5 of the aromatic ring),
7.89 (m, 2H, H2 and H6 of the aromatic ring). 13C NMR
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140.9, 171.1. MS m/z: 271 [M+]. Anal. calcd. for
C12H17NO4S: C 53.12, H 6.32, N 5.16; found: C 53.30, H
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Butyl 3-(4-methylphenylsulfonamido)propanoate (1i)
Pale yellow oil; isolated yield: 0.460 g (77%). IR
(neat, cm–1): 3286, 3044, 2960, 1732, 1330. 1H NMR
(CDCl3, ppm) δ: 0.89 (t, 3H, J = 6.8 Hz, CH2(CH2)2CH3),
1.33 (m, 2H, CH3CH2), 1.56 (m, 2H, CH3CH2CH2), 2.40 (s,
3H, ArCH3), 2.51 (t, 2H, J = 5.3 Hz, O=CCH2), 3.16 (t, 2H,
J = 5.3 Hz, O=CCH2CH2), 4.04 (t, 2H, J = 7.0 Hz, OCH2),
5.76 (s, 1H, NH), 7.33 (d, 2H, J = 7.9 Hz, H3 and H5 of the
aromatic ring), 7.72 (d, 2H, J = 7.9 Hz, H2 and H6 of the ar-
omatic ring). 13C NMR (CDCl3) δ: 13.5, 18.9, 21.3, 30.3,
34.1, 38.7, 64.5, 126.9, 129.6, 135.8, 143.2, 172.7. MS m/z:
299 [M+]. Anal. calcd. for C14H21NO4S: C 56.16, H 7.07, N
4.68; found: C 55.97, H 7.18, N 4.55.
Compound 2i
Pale yellow oil; isolated yield: 0.071 g (8%). IR
(neat, cm–1): 3056, 2975, 1734, 1317. 1H NMR (CDCl3,
ppm) δ: 0.92 (t, 6H, J = 6.9 Hz, 2CH2(CH2)2CH3), 1.32 (m,
4H, 2CH3CH2), 1.57 (m, 4H, 2CH3CH2CH2), 2.42 (s, 3H,
ArCH3), 2.63 (t, 4H, J = 5.2 Hz, 2O=CCH2), 3.43 (t, 4H, J =
5.2 Hz, 2O=CCH2CH2), 4.02 (t, 4H, J = 7.0 Hz, 2OCH2),
© 2007 NRC Canada

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