Bioglycerol-based sulfonic acid-functionalized carbon catalyst as an efficient and reusable catalyst for one-pot synthesis of 3- substituted-2 h -1,4-benzothiazines

Article abstract of DOI:10.1080/10426507.2013.765873

A simple and efficient synthetic protocol has been developed for the synthesis of 3-substituted-2H-1,4-benzothiazines by using bioglycerol-based sulfonic acid-functionalized carbon catalyst, devoid of corrosive acidic and basic reagents. The developed met

Full text of DOI:10.1080/10426507.2013.765873

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Phosphorus, Sulfur, and Silicon and the
Related Elements
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Bioglycerol-Based Sulfonic Acid-
Functionalized Carbon Catalyst as an
Efficient and Reusable Catalyst for One-
Pot Synthesis of 3- Substituted-2H-1,4-
Benzothiazines
Xiaojuan Yang a & Liqiang Wu b
a College of Chemistry and Chemical Engineering , Xinxiang
University , Xinxiang , Henan , 453003 , P.R. China
b School of Pharmacy , Xinxiang Medical University , Xinxiang ,
Henan , 453003 , P.R. China
Accepted author version posted online: 25 Feb 2013.Published
online: 06 Sep 2013.
To cite this article: Xiaojuan Yang & Liqiang Wu (2013) Bioglycerol-Based Sulfonic Acid-Functionalized
Carbon Catalyst as an Efficient and Reusable Catalyst for One-Pot Synthesis of 3- Substituted-2H-1,4-
Benzothiazines, Phosphorus, Sulfur, and Silicon and the Related Elements, 188:10, 1327-1333, DOI:
10.1080/10426507.2013.765873
To link to this article: http://dx.doi.org/10.1080/10426507.2013.765873
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Phosphorus, Sulfur, and Silicon, 188:1327–1333, 2013
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2013.765873
BIOGLYCEROL-BASED SULFONIC
ACID-FUNCTIONALIZED CARBON CATALYST
AS AN EFFICIENT AND REUSABLE CATALYST
FOR ONE-POT SYNTHESIS
OF 3- SUBSTITUTED-2H-1,4-BENZOTHIAZINES
Xiaojuan Yang1 and Liqiang Wu2
1College of Chemistry and Chemical Engineering, Xinxiang University, Xinxiang,
Henan 453003, P.R. China
2School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003,
P.R. China
GRAPHICAL ABSTRACT
Abstract A simple and efficient synthetic protocol has been developed for the synthesis of
3-substituted-2H-1,4-benzothiazines by using bioglycerol-based sulfonic acid-functionalized
carbon catalyst, devoid of corrosive acidic and basic reagents. The developed method has
the advantages of good to excellent yields, short reaction times, operational simplicity, and a
recyclable catalyst.
Keywords Bioglycerol-based sulfonic acid-functionalized carbon catalyst; 1,4-benzothiazine;
o-aminothiophenol; ω-bromoketone
INTRODUCTION
1,4-Benzothiazines are a class of N-heterocycles that have attracted much attention
because of their broad range of pharmacological properties, such as antifungal,1,2 immunos-
timulating,3 antirheumatic,4 antiallergic,5 and antitumor activities.6 1,4-Benzothiazines pro-
vide privileged scaffolds in lead identification/drug discovery programs and have provided
therapeutically useful compounds such as antirheumatic agents (e.g., MX-684), histamine
Received 10 October 2012; accepted 9 January 2013.
Address correspondence to Liqiang Wu, School of Pharmacy, Xinxiang Medical University, Xinxiang,
Henan 453003, P.R. China. E-mail: wliq1974@sohu.com; wuliqiang@xxmu.edu.cn
1327

1328
X. YANG AND L. WU
H1-receptor antagonist (e.g., VUF-K-87885), aldose reductase inhibitors, which are very
promising for treating hyperglycemia (e.g., SPR-2107), and Ca2+ channel antagonists (e.g.,
semotiadil fumarate8).
Several methods have been reported for the synthesis of 1,4-benzothiazine com-
pounds, including the ring expansion of benzothiazoles or benzothiazolines,9,10 base-
mediated reactions of o-aminothiophenols with ω-bromoacetophenones,11 HCl-catalyzed
reactions of o-nitrobenzenesulfenyl chlorides with ketones,12 by treatment of aminoth-
ioalkenols with p-TsOH or H3PO4,13 by reaction of bis(o-aminophenyl)-disulfide with ke-
tones,14 by the condensation of o-aminothiophenols and 2-bromo-1-aryl-ethanones using
KHSO4,15 and via simultaneous reduction of nitro group and S–S bond in nitrodisulfides
induced by low-valent titanium reagent.16 All these procedures have certain limitations,
such as tedious processes,11,14 long reaction times,11,13 harsh reaction conditions,9–12,16 and
low yields.9–11,16
In recent times, the development of an environmentally benign, green, and easily
recyclable catalyst for the production of fine chemicals has been an area of growing interest.
In this context, carbon-based solid acid catalysts play a prominent role in the organic
synthesis under heterogeneous reaction conditions.17–20 They are insoluble in common
organic solvents, cause low corrosion, and show environmental acceptability. Also, the
products could be easily separated from the reaction mixture and the catalyst is recoverable
without any decrease in its activity. Therefore, it can be successfully used instead of sulfuric
acid as a catalyst.21–23
In connection with our previous work on the synthesis of pharmaceutically impor-
tant heterocyclic compounds, herein, we wish to report the new efficient synthesis of 3-
substituted-2H-1,4-benzothiazines from aromatic aminothiophenols and ω-bromoketones
using bioglycerol-based sulfonic acid-functionalized carbon catalyst (Scheme 1).
Scheme 1
RESULTS AND DISCUSSION
To optimize the reaction conditions, we conducted the reaction of o-aminothiophenol
with 2-bromo-1-phenyl-ethanone using 100 mg/mmol of bioglycerol-based sulfonic acid-
functionalized carbon catalyst in various solvents such as MeOH, EtOH, H2O, CH3CN,
CH2Cl2, and dimethylformamide (DMF). The results showed that the highest product yield
was obtained in CH3CN (Table 1, entry 3). Then, the effect of the amount of catalyst on
the conversion rate of the reaction was studied by varying the amount of the bioglycerol-
based sulfonic acid-functionalized carbon catalyst under reflux (Table 1). It was found

BIOGLYCEROL–BASED SULFONIC ACID FUNCTIONALIZED CARBON
1329
Table 1 Optimization of reaction conditions for synthesis of 3-phenyl-2H-1,4- benzothiazinea
Bioglycerol-based
sulfonic acid (mg/mmol)
Entry
conditions
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
9
CH3CN (reflux)
CH3CN (reflux)
CH3CN (reflux)
CH3CN (reflux)
CH3CN (reflux)
MeOH (reflux)
EtOH (reflux)
CH2Cl2 (reflux)
H2O (reflux)
—
50
24
4
3
3
3
7
6
8
24
4
42
79
96
95
96
65
73
72
16
77
80
100
150
200
100
100
100
100
100
100
10
11
DMF (80◦C)
DMF (100◦C)
4
aReaction conditions: o-aminothiophenol (1 mmol), 2-bromo-1-phenyl-ethanone (1 mmol).
bIsolated yield.
that 100 mg/mmol of bioglycerol-based sulfonic acid-functionalized carbon catalyst was
sufficient to carry out this reaction smoothly. An increase in the amount of bioglycerol-
based sulfonic acid-functionalized carbon catalyst to more than 100 mg/mmol showed no
substantial improvement in the yield.
To show the generality of this method, a range of 3-substituted-2H-1,4- benzoth-
iazines were prepared under the optimized reaction conditions. In all cases, the yields ob-
tained were good to excellent, without the formation of any side products. Also, aromatic
ω-bromoketone with substituents carrying either electron-donating or electron-withdrawing
groups reacted successfully and gave the expected products in good to excellent yields in
relatively short reaction times. Although the kind of ω-bromoketone has no significant effect
on the reaction, the results in Table 2 show that the aromatic ω-bromoketones react faster
and the yields are slightly more than the aliphatic ω-bromoketone, 1-bromopropan-2-one
(Table 2, entry 12).
The formation of the product may be explained by the reaction of ω-bromoketone 2
with bioglycerol-based sulfonic acid-functionalized carbon that leads to the formation of an
oxonium ion. Later, the ion reacts with 4-substituted o-aminothiophenol 1 and undergoes
subsequent cyclization to form the expected product (Scheme 2).
The recyclability of the catalyst was investigated by using a model reaction between
o-aminothiophenol and 2-bromo-1-phenyl-ethanone in the presence of bioglycerol-based
sulfonic acid-functionalized carbon catalyst (Figure 1). After completion of the reaction,
the catalyst was filtered, washed with ethyl acetate and acetone, and dried under reduced
pressure. The catalyst was reused for the same reaction without further activation. The
reaction proceeded smoothly even after six cycles, without any extension of the reaction
time or marked loss in the yield.
To illustrate the efficiency of the proposed method, Table 3 compares some of our
results with some of those reported for relevant reagents in the literature, which demon-
strates its significant superiority. Compared with some of the reported methods in Table 3,
the present method has a short reaction time and a good yield. In addition, bioglycerol-
based sulfonic acid-functionalized carbon catalyst is a stable, cost-effective, recyclable, and
noncorrosive catalyst with high efficiency.

1330
X. YANG AND L. WU
Scheme 2
EXPERIMENTAL
Infrared (IR) spectra were determined on an FTS-40 infrared spectrometer. 1H NMR
spectra were determined on a Bruker AV-400 spectrometer at room temperature (r.t.) using
using tetramethylsilane (TMS) as an internal standard (CDCl3 solution); coupling constants
(J) were measured in Hertz. Elemental analysis were performed by a Vario-III elemental
analyzer. Melting points were determined on an XT-4 binocular microscope and were
uncorrected. The bioglycero- based sulfonic acid carbon reagent was prepared by the
reported procedure.17
Table 2 Preparation of 3-substituted-2H-1,4-benzothiazinesa
Entry
R1
R2
Time (h)
Product
Yield (%)b
mp (◦C) (Ref.)c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
H
H
H
H
H
H
H
H
H
C6H5
3
3
2
4
4
4
5
4
5
6
4
12
2
3
3
3
3
5
3
4
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
3s
96
95
98
92
96
88
91
92
86
84
89
80
94
92
90
91
89
85
88
90
44–45 (46–48)16
52–53 (52–54)16
4-Me-C6H4
4-MeO-C6H4
4-F-C6H4
99–101 (98–100)24
185–187 (187–188)11
55–56 (56–58)16
4-Cl-C6H4
4-Br-C6H4
4-NO2-C6H4
2-MeO-C6H4
3-NO2-C6H4
3,4,5-(MeO)3-C6H2
2-benzofuryl
CH3
59–61 (60–62)16
119–121 (120–122)24
136–138 (137.5–138)11
88–87 (86–88)25
H
H
155–157 (157–158)11
86–87 (86–88)16
Cl
Cl
Cl
Cl
Cl
Cl
Cl
CF3
CF3
oil (oil)16
C6H5
62–63 (62–64)16
4-Me-C6H4
4-MeO-C6H4
4-Cl-C6H4
4-Br-C6H4
2-benzofuryl
C6H5
121–125 (122–124)16
116–118 (117–119)16
120–122 (119–121)16
154–156 (155–158)16
124–125 (125–127)16
84–85 (83.5–84)11
170–172 (171–172.5)11
4-MeO-C6H4
3t
aReaction conditions: 4-substituted o-aminothiophenol (1 mmol), ω-bromoketones (1 mmol); bioglycerol-
based sulfonic acid-functionalized carbon catalyst (100 mg); CH3CN (10 mL); reflux.
bIsolated yield.
cThe range in parentheses means melting point of reference.

BIOGLYCEROL–BASED SULFONIC ACID FUNCTIONALIZED CARBON
1331
Figure 1 Reusability of bioglycerol-based sulfonic acid-functionalized carbon catalyst synthesis of 3-phenyl-
2H-1,4-benzothiazine (Color figure available online).
Typical Procedure for the Preparation of 3a
To a suspension of 2-bromo-1-phenyl-ethanone (1 mmol) and bioglycerol-based sul-
fonic acid-functionalized carbon catalyst (100 mg) in CH3CN (10 mL), o-aminothiophenol
(1 mmol) was added slowly and the mixture was stirred at reflux temperature. The reaction
was monitored by thin-layer chromatography (TLC) [ethyl acetate and cyclohexane (v:v =
1:7)]. After completion, the reaction mixture was filtered. The catalyst was washed with
ethyl acetate and acetone, dried under reduced pressure dried, and reused for a consecutive
run under the same reaction conditions. Evaporation of the solvent, followed by recrystal-
lization from ethyl acetate, gave the desired product 3a in good to high yields. The desired
pure products were characterized by comparison of their NMR data with those of known
compounds. The spectral data of some selected compounds are given below.
3-Phenyl-2H-1,4-benzothiazine (3a): IR (KBr) ν: 2928, 1638, 1463, 776 cm−1; 1H
NMR (400 MHz, CDCl3): 7.46–6.90 (m, 9H, Ar), 3.82 (s, 2H, CH2); Anal. Calcd. for
C14H11NS: C 74., 63, H 4.92, N 6.22, S 14.23; Found: C 75.02, H 4.99, N 6.19, S 14.20.
3-(2ꢁ-Benzofuryl-2H-1,4-benzothiazine (3k): IR (KBr) ν: 2933, 1669, 1472, 1246,
762 cm−1; 1H NMR (400MHz, CDCl3): 8.02–6.91 (m, 7H, Ar), 3.67 (s, 2H, CH2); Anal.
Calcd. for C12H9NOS: C 66.95, H 4.21, N 6.51, S 14.90; Found: C 67.02, H 4.18, N 6.54,
S 14.97.
Table 3 Comparison of bioglycerol-based sulfonic acid-functionalized carbon catalyst-catalyzed synthesis
of 3a
Entry
Catalyst and conditions
Solvent
Time (h)
Yield (%)
Ref.
1
2
3
KHSO4 (10 mol%); reflux
CH3CN
Et2O
CH3CN
4
24
3
95
58
96
15
11a
This work
Catalyst-free; nitrogen atmosphere; r.t.
Bioglycerol-based carbon catalyst
(10 mg/mmol); reflux
ao-Aminothiophenol as sodium 2-aminothiophenate.

1332
X. YANG AND L. WU
6-Chloro-3-methyl-2H-1,4-benzothiazine (3l): IR (KBr) ν: 2986, 2922, 1655, 1472,
1
1369, 766, 741 cm−1; H NMR (400 MHz, CDCl3): 7.55–6.87 (m, 3H, Ar), 2.75 (s, 2H,
CH2), 2.09 (s, 3H, CH3); Anal. Calcd. for C9H8ClNS: C 54.68, H 4.08, N 7.09, S 16.22;
Found: C 54.72, H 4.00, N 7.13, S 16.25.
6- Chloro-3-phenyl-2H-1,4- benzothiazine (3m): IR (KBr) ν: 2932, 1649, 1477,
767, 738 cm−1; 1H NMR (400 MHz, CDCl3): 7.49–6.82 (m, 8H, Ar), 3.82 (s, 2H, CH2);
Anal. Calcd. for C14H10ClNS: C 64.73, H 3.88, N 5.39, S 12.34; Found: C 64.82, H 3., 79,
N 5.42, S 12.38.
CONCLUSION
In conclusion, we have demonstrated a mild and highly efficient protocol for the
synthesis of 3-substituted-2H-1,4-benzothiazines by using a novel recyclable bioglycerol-
based carbon catalyst in CH3CN as a reaction medium. The catalyst can be reused after a
simple work-up. Other advantages of this protocol are high yields, short reaction time, easy
work-up, environmental acceptability, and cleaner reaction profiles.
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