Ultrasound accelerated sulfonylation of amines by p-acetamidobenzenesulfonyl chloride using Mg–Al hydrotalcite as an efficient green base catalyst

Article abstract of DOI:10.1080/17415993.2016.1193180

The sulfonylation reaction of various aliphatic, alicyclic, aromatic, and hetero-aromatic amines with p-acetamidobenzenesulfonyl chloride has been investigated using different types of base catalysis under varied reaction conditions. Mg–Al hydrotalcite, characterizable as an inexpensive, reusable, and green solid catalyst, was found to be the most efficient catalyst, when the reaction is carried out in a minimum volume of solvent (acetone). The reaction was found to be accelerated drastically with the support of ultrasound irradiation, affording the sulfonamides in yields better or equivalent to those obtained under the longer lasting conventional stirring conditions.

Full text of DOI:10.1080/17415993.2016.1193180

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Ultrasound accelerated sulfonylation of amines by
p-acetamidobenzenesulfonyl chloride using Mg–Al
hydrotalcite as an efficient green base catalyst
Binh Nhat Truong, Luong Huu Le, Duy-Khiem Nguyen Chau, Fritz Duus &
Thi Xuan Thi Luu
To cite this article: Binh Nhat Truong, Luong Huu Le, Duy-Khiem Nguyen Chau, Fritz
Duus & Thi Xuan Thi Luu (2016): Ultrasound accelerated sulfonylation of amines by p-
acetamidobenzenesulfonyl chloride using Mg–Al hydrotalcite as an efficient green base
catalyst, Journal of Sulfur Chemistry, DOI: 10.1080/17415993.2016.1193180
To link to this article: http://dx.doi.org/10.1080/17415993.2016.1193180
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Date: 27 June 2016, At: 19:41

JOURNAL OF SULFUR CHEMISTRY, 2016
http://dx.doi.org/10.1080/17415993.2016.1193180
Ultrasound accelerated sulfonylation of amines by
p-acetamidobenzenesulfonyl chloride using Mg–Al
hydrotalcite as an efficient green base catalyst
Binh Nhat Truonga, Luong Huu Lea, Duy-Khiem Nguyen Chaua, Fritz Duusb and
Thi Xuan Thi Luua
aDepartment of Organic Chemistry, National University of Science of Ho Chi Minh City, Ho Chi Minh City,
Vietnam; bDepartment of Science, Systems and Models, Roskilde University, Roskilde, Denmark
ABSTRACT
ARTICLE HISTORY
Received 16 March 2016
Accepted 19 May 2016
The sulfonylation reaction of various aliphatic, alicyclic, aromatic, and
hetero-aromatic amines with p-acetamidobenzenesulfonyl chloride
has been investigated using different types of base catalysis under
varied reaction conditions. Mg–Al hydrotalcite, characterizable as an
inexpensive, reusable, and green solid catalyst, was found to be the
most efficient catalyst, when the reaction is carried out in a minimum
volume of solvent (acetone). The reaction was found to be acceler-
ated drastically with the support of ultrasound irradiation, affording
the sulfonamides in yields better or equivalent to those obtained
under the longer lasting conventional stirring conditions.
KEYWORDS
Mg–Al hydrotalcite;
sulfonamide synthesis;
disulfonylation of amine;
desulfonylation; ultrasound
irradiation
1. Introduction
Sulfonamides (general formula: R1-SO2-NR2R3), the amides of sulfonic acids, can be clas-
sified as un-substituted (R2 = R3 = H), mono-substituted (R3 = H), or di-substituted
(R2, R3
ꢀ= H) sulfonamides, depending on the number of groups attached to
nitrogen. They make up the oldest group of synthetic anti-microbacterial com-
pounds that has been procured and developed during more than 80 years. The
first sulfonamide recognized to have anti-microbacterial efficiency, i.e. Prontosil
(4-[(2,4-diaminophenyl)azo]benzenesulfonamide) was discovered in 1932; however, its
mode of biological action by releasing the actually active compound sulfanilamide
(4-aminobenzenesulfonamide) was not perceived for next 20 years.[1,2] Sulfonamides
have been used intensively as antibacterial agents,[3–6] carbonic anhydrase inhibitors
(CAs) and COX-II inhibitors,[7,8] cysteine protease inhibitors,[9,10] and pharmaceuticals
CONTACT Thi Xuan Thi Luu
ltxthi@hcmus.edu.vn
Supplemental data for this article can be accessed here. http://dx.doi.org/10.1080/17415993.2016.1193180
© 2016 Informa UK Limited, trading as Taylor & Francis Group

2
B. N. TRUONG ET AL.
agents for many other categories of disease.[11–14] Today sulfa drugs have been replaced
considerably by safer and more powerful antibiotics; however, they are still used exclusively
against urinary tract infections.[3,15] From a chemical point of view, the sulfonamides
have frequently been regarded as the most convenient and efficient form for preservation of
amines because of their stability, combined with the fact that the amines can be regenerated
easily by desulfonylation under mild reaction conditions.[16–19]
Since derivatives of sulfanilamide (4-aminobenzenesulfonamide) are structurally
related to the p-aminobenzoic acid analogs (components necessary for the synthesis of
folic acid in bacteria), the corresponding sulfa drugs have been prepared analogously by
reaction of p-acetamidobenzenesulfonyl chloride with ammonia or other relevant amines,
to give the desired sulfonamides. Subsequent convenient base catalyzed hydrolysis of the
p-acetamido-groups yields the desired sulfa drug without severe consequences for the
survival of the sulfonamide group.[3]
A great number of methods for the synthesis of sulfonamides have been developed using
a variety of starting materials, e.g. sulfonic acids,[20–23] sulfonic acid esters,[24–27] and
sulfonyl chlorides.[28–41] Other synthetic routes to sulfonamides depend on the electro-
chemical oxidation of amine derivatives in the presence of arenesulfinic acid,[42–46] and
the direct conversion of thiols into sulfonamides by treatment successively with hydrogen
peroxide, thionyl chloride, and the pertinent amine.[47]
Evidently, the base-catalyzed sulfonylation of amines by means of sulfonyl chlorides has
been the preferred method of choice owing to its efficiency and simplicity, whether by use
of homogeneous organic base catalysts such as pyridine,[13,28] triethylamine,[6,29,30]
1,8-diaza-bicyclo[5.4.0]undec-7-ene (DBU),[31] and other amine reagents,[32,33] or by
use of various heterogeneous catalysts found to be excellent alternatives because of the
easy isolation of the product,[34–37] as well as with respect to the renewal of the catalytic
activity.[38–41]
On this background and with sympathy for the principles of green chemistry,[48,49]
we found it relevant to investigate the reactivity of p-acetamidobenzenesulfonyl chloride
(a most pertinent sulfonyl chloride, cf. statement above) toward a selection of aliphatic,
alicyclic, aromatic, and hetero-aromatic amines. Mg–Al hydrotalcite was chosen as the
primary heterogeneous catalyst to be tested in comparison with KF/alumina as well as
some organic catalysts [triethylamine and 4-dimethylaminopyridine (DMAP)] owing to
the inexpensiveness, stability, and large applications of Mg–Al hydrotalcite in organic
syntheses.[50–53] Furthermore, the effect of using ultrasound irradiation was also taken
into consideration as a green source of energy supply.[48,49]
2. Result and discussion
At the beginning of this research work, the solvent-free reactions of p-acetamido-
benzenesulfonyl chloride with cyclohexylamine and 2-aminothiazole were respectively
tested. However, incomplete reaction conversion and moderate yields of the sulfonamides
forced us to turn our attention to survey a qualified solvent for these reactions. The results
demonstrated that acetone appeared to be the best solvent in competition with acetonitrile,
dioxane, ethyl acetate, and dichloromethane.
The sulfonylation of amines liberates hydrogen chloride during the reaction, therefore
two equivalents of the amine must be used. In general, because the amine component is

JOURNAL OF SULFUR CHEMISTRY
3
Table 1. Influence of the nature of the base catalyst on the yields of the p-acetamido-
benzenesulfonamides obtained by the reactions of p-acetamidobenzenesulfonyl chloride with
cyclohexylamine and 2-aminothiazole, respectively under specified reaction conditions.a
Entry
Amine (mmol)
Catalyst (mmol)
Time (h)
Yield (%)b
1
2
3
4
None
3
4
0.75
0.75
56
81
86
60
Mg–Al hydrotalcite (0.4)
Mg–Al hydrotalcite (0.4)c
KF/alumina (1)c
5
6
7
8
9
10
None
4
4
4
4
4
4
27
73
52
53
52
73
Mg–Al hydrotalcite (0.4)
KF/alumina (2)
Triethylamine (2)
4-Dimethylaminopyridine (DMAP) (2)
Mg–Al hydrotalcite (0.4) and triethylamine (2)
11
Mg–Al hydrotalcite (0.8)
4
71
aThe reaction of p-acetamidobenzenesulfonyl chloride (2 mmol) with cyclohexylamine or 2-aminothiazole dissolved in
acetone (1.5 mL) was performed under stirring at room temperature.
bYield of isolated product.
cThe reaction was assisted by ultrasound irradiation.
valuable, sulfonamide synthesis is often carried out using one equivalent of the amine plus
a corresponding amount of an inexpensive base. A selected variety of catalysts were tested
for the sulfonylation of cyclohexylamine (2a) and 2-aminothiazole (2f) by an equimolar
amount of p-acetamidobenzenesulfonyl chloride (1) in acetone solution at room tem-
perature under magnetic stirring or ultrasound irradiation (Table 1). Finally, Mg–Al
hydrotalcite was selected as the supporting base catalyst owing to its good influence on
the yield of the sulfonamide products.
The introductory experiments also disclosed that the two amines (cyclohexylamine
and 2-aminothiazole) react differently with equimolar amounts of p-acetamidobenzene-
sulfonyl chloride: cyclohexylamine undergoes a monosulfonylation reaction, whereas
2-aminothiazole apparently preferably undergoes a double sulfonylation reaction.
Further experiments disclosed quite clearly that aliphatic, alicyclic, and also the
aromatic amine 3,5-bis(trifluoromethyl)aniline react with an equimolar amount of
p-acetamidobenzenesulfonyl chloride in a minimum amount of acetone (solvent) and in
the presence of the solid catalyst Mg–Al hydrotalcite to form exclusively the correspond-
ing monosulfonylated amines, i.e. the corresponding p-acetamidobenzenesulfonamides
(Scheme 1, Table 2).
On the other hand, the medicinal importance of hetero-aromatic sulfonamides (the
‘sulfa drugs’ [54]) made us curious to investigate also the conversion of the three
hetero-aromatic amines (2-aminothiazole, 2-amino-5-methylthiazole, and 2-amino-5-
methylthio-1,3,4-thiadiazole) into the corresponding sulfonamides under the same reac-
tion conditions as described above. Surprisingly, but in accord with the above-mentioned
observation concerning the sulfonylation of 2-aminothiazole, all three hetero-aromatic

4
B. N. TRUONG ET AL.
Scheme 1. Monosulfonylated products obtained from the reaction of p-acetamidobenzenesulfonyl
chloride with aliphatic, cyclic, and aromatic amines.
Table 2. Yields of monosulfonylated compounds from the reaction of p-acetamidobenzenesulfonyl
chloride with aliphatic, alicyclic, and aromatic amines.a
Yield (%)b (Time)c
Entry
1
Amine
Product
Method Aa
91 (6)
Method Ba
92 (0.25)
2
3
59 (6)
63 (6)
71 (0.5)
76 (0.5)
4
5
51 (6)
54 (6)
56 (0.5)
63 (0.5)
aThe reaction of p-acetamidobenzenesulfonyl chloride (2 mmol) with amine (2 mmol) catalyzed by Mg–Al hydrotalcite
(0.4 mmol, 0.24 g) dissolved in acetone (1.5 mL) was performed under magnetic stirring at room temperature (Method
A) or under ultrasound irradiation (Method B).
bYield of isolated product.
cTime = reaction time in hours.
amines underwent exclusively the double sulfonylation reaction to form as the only prod-
uct, the 2-[bis-(p-acetamidobenzenesulfonyl)amino]-hetero-aromatic compounds 3f, 3g
and 3h, respectively, in fair yields (Scheme 2, Table 3).

JOURNAL OF SULFUR CHEMISTRY
5
Scheme 2. Synthetic pathway of sulfanilamides from p-acetamidobenzenesulfonyl chloride and
hetero-aromatic amines.
Table 3. Yieldsofdisulfonylatedcompoundsfromthereactionofp-acetamidobenzenesulfonylchloride
and hetero-aromatic amines.a
Yield (%)b (Time)c
Entry
1
Amine
Product
Method Ca
71 (0.5)
Method Da
74 (0.17)
2
74 (4)
77 (1.25)
3
39 (5)
40 (3.25)
aThe reaction of p-acetamidobenzenesulfonyl chloride (2 mmol) with amine (1 mmol) catalyzed by Mg–Al hydrotalcite
(0.8 mmol, 0.48 g) dissolved in acetone (1.5 mL) was performed under magnetic stirring at room temperature (Method
C) or under ultrasound irradiation (Method D).
bYield of isolated products.
cTime = reaction time in hours.
Evidently, either monosulfonylation or disulfonylation can take place, depending on the
nature of the amine. The formation of a mixture of the two types of product was never
observed. It was therefore concluded that, in the case of the disulfonylation reaction, a
previous monosulfonylation reaction must have occurred, leading to a monosulfonylated

6
B. N. TRUONG ET AL.
Scheme 3. A plausible mechanism for the double sulfonylation of the hetero-aromatic amines (2f–2h)
using Mg–Al hydrotalcite.
species being more reactive toward sulfonylation than the hetero-aromatic amine itself.
This species can be derived only from the monosulfonylated hetero-aromatic amine R2-
SO2-NH-R1 (cf. Scheme 3), where R1 is the hetero-aromatic group. A recent investigation
of the acidities of p-aminobenzenesulfonylated hetero-aromatic amines has demonstrated
that the hydrogen atom attached to nitrogen is quite acidic (pKa-values ranging from
5.2 to 7.4).[54] In the presence of the solid base catalyst Mg–Al hydrotalcite, the mono-
sulfonylated hetero-aromatic amine is likely to be transformed into the anionic species
R2-SO2-N−-R1, which will be a more aggressive species toward the sulfonyl chloride
than the hetero-aromatic amine, and therefore give rise to the formation of the observed
disulfonylated product (Scheme 3).
It should be noticed that the sulfonylation reactions of the hetero-aromatic amines were
constantly monitored by TLC (thin layer chromatography) as well as by the analysis of
the crude products by HPLC (high-performance liquid chromatography). In no case even
traces of a monosulfonylated hetero-aromatic amine could be detected.
Altogether five simple amines and three hetero-aromatic amines were subjected to sul-
fonylation by p-acetamidobenzenesulfonyl chloride in a minimum amount of acetone,
using two different methods. In the first series of sulfonylation reactions, where the mix-
ture of reactants was simply stirred magnetically at room temperature (Method A), fair to
high yields were obtained in all cases. The next series of the sulfonylation was performed
as described in Method A, but under the assistance of ultrasound irradiation replacing
the magnetic stirring (Method B). Although the yields of the products were only slightly
improved, the reaction times were shortened considerably in comparison with those under
the magnetic stirring method. Due to cavitation collapse in a liquid near a solid surface,
high pressure and high temperature are generated shortly and hit the surface of Mg–Al
hydrotalcite particles to cause the renewal of its reactive surface area, reduction in Mg–Al
hydrotalcite particle size and great enhancement of mixing.[48]
In the hydrolysis step of the p-acetamido-groups by means of a base catalyst, e.g. the
disulfonylated products formed were easily transformed into desired monosulfonylated

JOURNAL OF SULFUR CHEMISTRY
7
Table 4. Yields of sulfanilamides from the base-catalyzed hydrolysis of disulfonylated compounds
(3f–3h).a
Entry
1
Disulfonylated compounds
Product
Yield (%)b
75
2
79
3
70
aOptimized hydrolysis reaction were performed with disulfonylated compounds (1 mmol) and 10% sodium hydroxide
solution (5 mL) for 45 min under stirring reflux at 75°C.
bYield of isolated products.
products in high yield (Table 4). A series of experiments were performed with tradi-
tional base catalytic solutions, e.g. aqueous saturated sodium carbonate solution or 10%
of sodium hydroxide solution under conventional heating at 65°C, 75°C, 85°C and 95°C,
or with solid base catalysts in solvent-free conditions, e.g. Mg–Al hydrotalcite or potas-
sium fluoride absorbed on alumina under the assistance of microwave irradiation at
100°C. Finally, sodium hydroxide solution was selected for the hydrolysis of disulfony-
lated hetero-aromatic amines (2f, 2 g, 2 h) owing to its good effects on the yield of desired
monosulfonylated products.
With the advantages of Mg–Al hydrotalcite on reactive enhancement, simple handling,
cheaper operation, and easy product isolation, the reusability of Mg–Al hydrotalcite was
paid attention to be examined. The Mg–Al hydrotalcite collected after filtration from the
previous reaction was washed with aqueous saturated sodium carbonate solution for 1 h at
room temperature, subsequently heated in oven at 100°C for 2 h, and obtained with 97%
of recycled yield. The structure of recovered catalyst was comparable with that of the fresh
Mg–Al hydrotalcite by the X-ray diffraction (XRD) pattern. The recycled Mg–Al hydro-
talcite was used for the sulfonylation of 2-aminothiazole with p-acetamidobenzenesulfonyl
chloride as that of the optimized experiment presented in Entry 1, Table 3. The catalytic
efficiency of Mg–Al hydrotalcite did not drop significantly even after seven runs of being
reused and recycled (Figure 1).

8
B. N. TRUONG ET AL.
Figure 1. Reusability of Mg–Al hydrotalcite (0.8 mmol, 0.48 g) in the sulfonylation of 2-aminothiazole
(1 mmol) with p-acetamidobenzenesulfonyl chloride (2 mmol) dissolved in acetone (1.5 mL) under half-
an-hour magnetic stirring.
3. Experimental design
3.1. Instrumentation and chemicals
3.1.1. Instrumentation
The reactions were carried out by means of a magnetic stirrer IKA Ret Basic C, speed-
ing at 250 rpm and a BRANSON 1510 ultrasonic bath, operating at frequency 40 kHz.
The progress of reaction was monitored by TLC on 60 F254 aluminum plates (Merck)
with detection by UV light. 1H NMR (500 MHz) and 13C NMR (125 MHz) spectra were
recorded on a Brüker Advance DPX 500 MHz spectrometer in DMSO with TMS as the
internal standard. HPLC/ESI (high-performance liquid chromatography/electrospray ion-
ization) analyses were performed on a TSQ 7000 (Thermo-Finnigan) instrument. Melting
points were determined on a Büchi B-545 melting point apparatus.
3.1.2. Chemicals
All commercially available chemicals used were from Aldrich and analyzed for authenticity
and purity by GC/MS (gas chromatography/mass spectrometry) before being used.
3.2. Typical procedures
3.2.1. The sulfonylation of aliphatic, cyclic, and aromatic amines (2a–2e) under
magnetic stirring (Method A)
A solution of the simple amine (2 mmol) in acetone (1.5 mL) was added into a 10 mL round
flask containing Mg–Al hydrotalcite (0.4 mmol, 0.24 g) and p-acetamidobenzenesulfonyl
chloride (2 mmol, 0.467 g). The reaction mixture was then stirred for six hours at room
temperature (Method A, Table 2). After reaction completion, the reaction mixture was

JOURNAL OF SULFUR CHEMISTRY
9
extracted with acetone (8 × 5 mL) and filtered to collect the solid base catalyst for recy-
cling and reuse. The filtrate was concentrated in vacuo, and then the residue after solvent
removal was washed with hot distilled water (70–80°C) to remove completely remain-
ing p-acetamido-benzenesulfonyl chloride or amine. The crude product was filtered, and
purified by recrystallization in ethanol/water to afford compounds (3a–3e) as white solid.
3.2.2. The sulfonylation of aliphatic, cyclic, and aromatic amines (2a–2e) under
ultrasound irradiation (Method B)
A solution the simple amine (2 mmol) in acetone (1.5 mL) was added into a 10 mL round
flask containing Mg–Al hydrotalcite (0.4 mmol, 0.24 g) and p-acetamidobenzenesulfonyl
chloride (2 mmol, 0.467 g). The reaction mixture was then irradiated ultrasonically for
the necessary period of reaction time (Method B, Table 2). After reaction completion, the
reaction mixture was worked up as in Method A.
3.2.3. The sulfonylation of hetero-aromatic amines (2f–2h) under magnetic stirring
(Method C)
A solution of the hetero-aromatic amine (1 mmol) in acetone (1.5 mL) was added into a
10 mL round flask containing also Mg–Al hydrotalcite (0.8 mmol, 0.48 g) and p-acetamido-
benzenesulfonyl chloride (2 mmol, 0.467 g). The reaction mixture was then stirred magnet-
ically for a specific period of time at room temperature (Method C, Table 3). After reaction
completion, the reaction mixture was worked up as in Method A.
3.2.4. The sulfonylation of hetero-aromatic amines (2f–2h) under ultrasound
irradiation (Method D)
A solution of the heterocyclic amine (1 mmol) in acetone (1.5 mL) was added
into a 10 mL round flask containing Mg–Al hydrotalcite (0.8 mmol, 0.48 g) and
p-acetamidobenzenesulfonyl chloride (2 mmol, 0.467 g). The flask was placed into an ultra-
sound bath where the mixture of reactants was exposed to ultrasound irradiation for a
specific period of time (Method B, Table 3). After reaction completion, the reaction mixture
was worked up as described for Method A.
3.2.5. Hydrolysis of disulfonylated compound (3f–3h)
A round-bottom flask (10 mL volume) was charged with the disulfonylated compound
(3f–3h) (1 mmol) and 10% aqueous sodium hydroxide (5 mL). The mixture was then
immersed in a preheated oil bath, heated to 75°C, and simultaneously stirred for 45 min.
After reaction completion, the resulting mixture was cooled to room temperature and acid-
ified by HCl aqueous solution (10%) until the mixture had pH 5. The pH of the mixture
was subsequently adjusted to just basic (checked by litmus) by adding solid sodium acetate,
and then this mixture was heated to boiling and filtered. The resulting filtrate was cooled
slowly first to room temperature and then further to 0°C in an ice bath. The final prod-
uct (4f–4h) was isolated by filtration as a yellowish solid and purified by re-crystallization
in ethanol/water or by flash column chromatography (7–8 g silica gel, Davisil, grade 710,
4–20 μm, 6 Å, 99%) using as eluent a mixture of dichloromethane and ethyl acetate
(5:5 v
/v).

10
B. N. TRUONG ET AL.
3.3. Spectroscopic data
The identity and purity of all products reported were confirmed by 1H-NMR, 13C-NMR
and HSQC spectroscopy, as well as by GC/MS or HPLC/MS. Since the derivatives of
p-acetamidobenzenesulfonamide are a large group and NMR spectroscopic data for 11
sulfonamides synthesized have not been well characterized spectroscopically, for which
reason full details of both the 1H-NMR spectra and the 13C-NMR spectra are presented
below.
3.3.1. N-cyclohexyl 4-(acetamido)benzenesulfonamide (3a)
1H NMR (500 MHz, DMSO-d6) δ (ppm) = 10.26 (s, 1H), 7.74 (d, 2H, J = 9 Hz), 7.72
(d, 2H, J = 9 Hz), 7.45 (d, 1H, J = 7.5 Hz), 2.89 (s, 1H), 2.08 (s, 3H), 1.54–1.56 (m, 4H),
1.41–1.43 (m, 1H), 0.99–1.14 (m, 5H).[55] MS (m/z): 253 [M].+, 198, 134, 98, 43.
3.3.2. N-phenyl 4-(acetamido)benzenesulfonamide (3b)
1H NMR (500 MHz, DMSO-d6) δ (ppm) = 10.27 (s, 1H), 10.13 (s, 1H), 7.69 (d, 2H,
J = 9.5 Hz), 7.67 (d, 2H, J = 9 Hz), 7.21 (t, 2H, J = 7 Hz), 7.07 (d, 2H, J = 8.5 Hz),
7.00 (t, 1H, J = 7.5 Hz), 2.05 (s, 3H). MS (ESI+): m/z 308.11 ([M+NH4]+, 100%),
291.08([M+H]+, 49%).
3.3.3. N-benzyl 4-(acetamido)benzenesulfonamide (3c)
1H NMR (500 MHz, DMSO-d6) δ (ppm) = 10.30 (s, 1H), 7.99 (t, 1H, J = 6.5 Hz), 7.75
(d, 2H, J = 9.5 Hz), 7.73 (d, 2H, J = 9 Hz), 7.20–7.30 (m, 5H), 3.95 (d, 2H, J = 6.5 Hz),
2.09 (s, 3H).[20] MS (ESI+): m/z 322.11 ([M+NH4]+, 100%), 305.10 ([M+H]+, 80%).
3.3.4. N-(3,5-bis(trifluoromethyl)phenyl) 4-(acetamido)benzenesulfonamide (3d)
M.p = 210–212°C (literature M.p = 211°C).[56] 1H NMR (500 MHz, DMSO-d6) δ
(ppm) = 11.12 (s, 1H), 10.35 (s, 1H), 7.75 (s, 4H), 7.72 (s, 1H), 7.64 (s, 2H), 2.05 (s, 3H).
13C NMR (125 MHz, DMSO-d6) δ (ppm) = 169.1, 143.7, 140.0, 131.8, 131.2, 128.0, 122.8,
118.8, 118.5, 116.5–116.7, 24.0. MS (ESI−): m/z 424.84 ([M-H]−, 81%), 228.11 (100%),
227.03 (85%), 226.06 (45%).
3.3.5. N-(sec-butyl) 4-(acetamido)benzenesulfonamide (3e)
1H NMR (500 MHz, DMSO-d6) δ (ppm) = 10.27 (s, 1H), 7.74 (d, 2H, J = 9 Hz), 7.71
(d, 2H, J = 9 Hz), 7.34 (d, 1H, J = 8 Hz), 3.01 (hept, 1H, J = 7 Hz), 2.08 (s, 3H), 1.28
(quint, 2H, J = 7 Hz), 0.85 (d, 3H, J = 7 Hz), 0.69 (t, 3H, J = 7 Hz). MS(ESI+): m/z 288.13
([M+NH4]+, 100%), 271.11 ([M+H]+, 90%).
3.3.6. N,N-bis(4-acetamidobenzenesulfonyl)-2-aminothiazole (3f)
M.p = 127–130°C (literature M.p = 127–129°C).[57] 1H NMR (500 MHz, DMSO-d6) δ
(ppm) = 10.44 (s, 1H), 10.26 (s, 1H), 7.82 (d, 2H, J = 9 Hz), 7.68 (d, 1H, J = 5 Hz), 7.67
(d, 2H, J = 9 Hz), 7.63 (d, 2H, J = 9 Hz), 7.47 (d, 2H, J = 9 Hz), 6.97 (d, 1H, J = 5 Hz),
2.12 (s, 3H), 2.08 (s, 3H). 13C NMR (125 MHz, DMSO-d6) δ (ppm) = 169.3, 168.9, 163.8,
145.7, 143.2, 133.8 (2C), 130.8, 126.9, 123.2, 118.3, 118.2, 107.7, 24.2, 24.1. MS (ESI+): m/z
517.11 ([M+Na]+, 100%), 495.14 [M+H]+, 72%), 198 (16%).

JOURNAL OF SULFUR CHEMISTRY
11
3.3.7. N,N-bis(4-acetamidobenzenesulfonyl)-2-amino-5-methylthiazole (3g)
1
Decomposed at 205°C. H NMR (500 MHz, DMSO-d6) δ (ppm) = 10.43 (s, 1H), 10.25
(s, 1H), 7.81 (d, 2H, J = 9 Hz), 7.68 (d, 2H, J = 9 Hz), 7.62 (d, 2H, J = 9 Hz), 7.50 (d, 1H,
J = 1.5 Hz), 7.47 (d, 2H, J = 9 Hz), 2.20 (d, 3H, J = 1.5 Hz), 2.12 (s, 3H), 2.08 (s, 3H).
13C NMR (125 MHz, DMSO-d6) δ (ppm) = 169.3, 168.9, 163.2, 145.6, 143.2, 133.9, 130.6,
127.2, 126.9, 119.0, 118.8, 118.3 (2C), 24.2, 24.1, 12.2. MS (ESI+): m/z 509.60 ([M+H]+,
12%), 198.03 (100%).
3.3.8. N,N-bis(4-acetamidobenzenesulfonyl)-2-amino-5-methylthio-1,3,4-thiadiazole
(3h)
De-composed at 173°C. 1H NMR (500 MHz, DMSO-d6) δ (ppm) = 10.31 (s, 1H), 10.00
(s, 1H), 7.70–7.75 (m, 4H), 7.50–7.54 (m, 4H), 2.64 (s, 3H), 2.07 (s, 3H), 2.04 (s, 3H).
13C NMR (125 MHz, DMSO-d6) δ (ppm) = 168.9, 168.3, 166.8, 155.1, 142.9, 142.6, 139.5,
135.5, 126.9, 126.1, 118.6, 117.9, 24.1, 24.0, 15.3. MS (ESI+): m/z 541.81 ([M+H]+, 8%),
198.06 (100%).
3.3.9. 2-(4-aminobenzenesulfonylamido)thiazole (4f)
1
M.p = 202–203°C (literature M.p = 202–203°C).[58,59] H NMR (500 MHz, DMSO-
d6) δ (ppm) = 12.40 (s, 1H), 7.44 (d, 2H, J = 9 Hz), 6.74 (d, 1H, J = 4.5 Hz), 6.56
(d, 2H, J = 9 Hz), 5.83 (s, 2H).[60] 13C NMR (125 MHz, DMSO-d6) δ (ppm) = 167.9,
152.2, 128.0, 127.7, 124.2, 112.5, 107.4.[61] MS (ESI+): m/z 255.99 ([M+H]+, 8%), 156.07
(100%), 92.22 (43%).
3.3.10. 2-(4-aminobenzenesulfonylamido)-5-methylthiazole (4g)
M.p = 247–249°C (literature M.p = 247°C).[62] 1H NMR (500 MHz, DMSO-d6) δ
(ppm) = 12.07 (s, 1H), 7.42 (d, 2H, J = 8.5 Hz), 6.90 (d, 1H, J = 1.5 Hz), 6.56 (d, 2H,
J = 8.5 Hz), 5.82 (s, 2H), 2.16 (d, 3H, J = 1.5 Hz). 13C NMR (125 MHz, DMSO-d6) δ
(ppm) = 167.2, 152.1, 128.2, 127.6, 119.9, 119.0, 112.5, 12.1. MS (ESI+): m/z 269.94
([M+H]+, 12%), 156.05 (100%), 92.21 (31%).
3.3.11. 2-(4-aminobenzenesulfonylamido)-5-methylthio-1,3,4-thiadiazole (4h)
M.p = 199–201°C (literature M.p = 198°C).[63] 1H NMR (500 MHz, DMSO-d6) δ
(ppm) = 7.41 (d, 2H, J = 8.5 Hz), 6.58 (d, 2H, J = 8.5 Hz), 2.63 (s, 3H). 13C NMR
(125 MHz, DMSO-d6) δ (ppm) = 165.8, 154.4, 152.7, 127.7, 126.9, 112.6, 15.2. MS (ESI+):
m/z 302.84 ([M+H]+, 7%), 156.05 (100%), 92.21 (22%).
4. Conclusion
An environmentally benign pathway to prepare common sulfonamides has been devel-
oped. Mg–Al hydrotalcite is commercially available, cheap, easy to store, and can be
recycled many times without any remarkable loss of activity. Moreover, ultrasound irra-
diation has good effects on the yields of sulfonamide products within a shorter reaction
time.

12
B. N. TRUONG ET AL.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding information
We are grateful to the National Foundation for Science and Technology Development (NAFOSTED)
under grant number 104.01-2011.40 for financial support.
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