Practical and efficient synthesis of 3-aryl-2H-benzo[1,4]thiazine derivatives catalyzed by KHSO4

Article abstract of DOI:10.1080/00397911003629465

KHSO₄ efficiently catalyzes the condensation of o-aminothiophenols and 2-bromo-1-aryl-ethanones to yield 3-aryl-2H-benzo[1,4] thiazines in good yields.

Full text of DOI:10.1080/00397911003629465

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Practical and Efficient Synthesis of 3-
Aryl-2H-benzo[1,4]thiazine Derivatives
Catalyzed by KHSO4
Bita Baghernejad a , Majid M. Heravi a & Hossein A. Oskooie a
a Department of Chemistry, School of Science, Azzahra University,
Vanak, Tehran, Iran
Published online: 02 Feb 2011.
To cite this article: Bita Baghernejad , Majid M. Heravi & Hossein A. Oskooie (2011) Practical and
Efficient Synthesis of 3-Aryl-2H-benzo[1,4]thiazine Derivatives Catalyzed by KHSO4 , Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
41:4, 589-593, DOI: 10.1080/00397911003629465
To link to this article: http://dx.doi.org/10.1080/00397911003629465
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Synthetic Communications1, 41: 589–593, 2011
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911003629465
PRACTICAL AND EFFICIENT SYNTHESIS OF
3-ARYL-2H-BENZO[1,4]THIAZINE DERIVATIVES
CATALYZED BY KHSO4
Bita Baghernejad, Majid M. Heravi, and Hossein A. Oskooie
Department of Chemistry, School of Science, Azzahra University, Vanak,
Tehran, Iran
Abstract KHSO4 efficiently catalyzes the condensation of o-aminothiophenols and
2-bromo-1-aryl-ethanones to yield 3-aryl-2H-benzo[1,4]thiazines in good yields.
Keywords o-Aminothiophenols; 3-aryl-2H-benzo[1,4]thiazine; KHSO4
INTRODUCTION
Benzofused heterocycles containing a sulfur moiety possess many biological
activities across a wide therapeutic fields, including vasodilator,[1] antidiabetic,[2]
anticataract,[3] and antiarrhythmic[4] activities. It is well known that benzothiazines
have enormous potential as pharmaceutical and agricultural agents because of their
biological activities. These compounds were reported as calcium channel blockers,[5]
phosphodiesterase inhibitors,[6] 5-HT3 antagonists,[7] anticataract agents,[8] dopa-
mine D4,[9] Naþ=Hþ exchange inhibitors,[10] coagulation factor Xa inhibitors,[11]
and matrix metalloproteinase inhibitors.[12] Therefore, a wide range of studies for
the synthetic development of benzothiazine derivatives have been carried out.[13–15]
We have also been interested in new synthetic studies of such benzothiazine deriva-
tives. As part of our program aimed at developing new methods for the preparation
of biologically active heterocycles,[16] we report a one-pot synthesis of 3-aryl-2H-
benzo[1,4]thiazine by the condensation of o-aminophenols and 2-bromo-1-aryl-
ethanones using KHSO4 as an efficient catalyst in good yields (Scheme 1).
Received December 7, 2009.
Address correspondence to Majid M. Heravi, Department of Chemistry, School of Science,
Azzahra University, Vanak, Tehran 1234, Iran. E-mail: mmh1331@yahoo.com
589

590
B. BAGHERNEJAD, M. M. HERAVI, AND H. A. OSKOOIE
Scheme 1.
RESULTS AND DISCUSSION
KHSO4 is one of the components of a triple salt with formula 2KHSO5 ꢀ
KHSO4 ꢀ K2SO4, a so-called oxone that is used as a highly efficient, mild, and sole
oxidizing agent in many organic reagents.[17] Very recently, we reported the use of
KHSO4 as an efficient catalyst for the synthesis of 1,1-diacetates under solvent-free
conditions.[18] As part of our program aimed at developing new, selective, and envir-
onmentally friendly methodologies for the preparation of fine chemicals, herein we
report an efficient and convenient procedure for the synthesis of 3-aryl-2H-
benzo[1,4]thiazines using KHSO4 as an efficient catalyst. In a typical procedure,
o-aminothiophenols (1 mmol) and 2-bromo-1-phenyl-ethanones (1 mmol) in the
presence of a catalytic amount of KHSO4 in CH3CN at reflux temperature afforded
the desired 3-aryl-2H-benzo[1,4]thiazine (3a) in 95% yield after 4 h (entry 1, Table 1).
To show the generality and scope of this new protocol, we used various
o-aminothiophenol and 2-bromo-1-aryl-ethanone compounds in the presence of
KHSO4, and the results obtained are summarized in Table 1.
Most of the reactions proceeded very cleanly at reflux temperature, and no
undesirable side reactions were observed. The variations in the yields were very little,
and substituted 2-bromo-1-aryl-ethanones such as 4-bromo and 4-methyl gave the
condensed products in good yields. We examined the effect of various solvents on
the synthesis of 3a. As shown in Table 2, this reaction results in good yields in a
range of solvents such as CH3CN, chloroform, ethanol, and CH2Cl2.
The reaction was studied with various amounts of KHSO4. Of all the cases,
10 mol% catalyst gave the maximum yield of products (Table 3).
Table 1. Synthesis of 3-aryl-2H-benzo[1,4]thiazine using KHSO4 under refluxing conditions
Mp (ꢁC)
Entry
R
R1
Product
Observed
Reported
Yield (%)a
1
2
3
4
5
6
7
8
H
H
H
Cl
3a
3b
3c
3d
3e
3f
49
58
47–48[19]
56–58[19]
59–61[19]
53–55[19]
64[19]
119–121[19]
155–158[19]
122–124[19]
95
96
97
96
93
92
93
90
H
Br
61
55
H
CH3
H
Cl
Cl
Cl
Cl
65
Cl
Br
120
158
124
3g
3h
CH3
aYields refer to isolated products.

SYNTHESIS OF 3-ARYL-2H-BENZO[1,4]THIAZINE
591
Table 2. Synthesis of 3a with KHSO4 in the presence of different solvents
Entry
Solvent
Temperature
Time (h)
Yield (%)a
1
2
3
4
CH3CN
Ethanol
CH2Cl2
Reflux
Reflux
Reflux
Reflux
4
5
6
6
95
91
90
89
Chloroform
aYield of isolated products.
Table 3. Synthesis of 3a using various amounts of KHSO4
Entry
KHSO4 (mol%)
Time (h)
Yield (%)a
1
2
3
4
No catalyst
5
24
4
50
88
95
95
10
15
4
4
aYield of isolated products.
Table 4. Reuse of KHSO4 for the synthesis of 3a
Entry
Time (h)
Yield (%)a
First
1
1
95
92
89
89
88
Second
Third
Fourth
Fifth
1.20
2
2.20
aIsolated yields.
Next, we investigated the reusability of KHSO4. When the reaction was com-
pleted, the catalyst was separated by simple filtration, recovered with CHCl3
(2 ꢂ 5 mL), and subsequently dried at 80 ꢁC to be reused. KHSO4 can be reused in sub-
sequent reactions without significant decrease in activity even after five runs (Table 4).
In conclusion, we have described a highly efficient procedure for the prep-
aration of 3-aryl-2H-benzo[1,4]thiazine using KHSO4 as a catalyst. The reaction
products were prepared in good yield. Moreover, the procedure offers several
advantages including good yields, operational simplicity, clean reaction, minimal
environmental impact, and low cost, which make it a useful and attractive process
for the synthesis of these compounds.
EXPERIMENTAL
All products are known compounds and were characterized by melting point
(mp), infrared (IR), 1H NMR, and gas chromatography=mass spectrometry
(GC=MS). Melting points were measured using the capillary tube method with an
1
Electrothermal 9200 apparatus. H NMR spectra were recorded on a Bruker AQS
Avance 300-MHz spectrometer using tetramethylsilane (TMS) as an internal

592
B. BAGHERNEJAD, M. M. HERAVI, AND H. A. OSKOOIE
standard (CDCl3 solution). IR spectra were recorded from KBr disk on the Fourier
transform (FT)–IR Bruker Tensor 27. GC=MS spectra were recorded on an Agilent
Technologies 6890 network GC system and an Agilent 5973 network mass selective
detector. Thin-layer chromatography (TLC) on commercial aluminum-backed plates
of silica gel, 60 F254, was used to monitor the progress of reactions. All products were
characterized by spectra and physical data.
Typical Procedure for the Synthesis of 3-Aryl-2H-benzo[1,4]thiazine
A mixture of 2-bromo-1-aryl-ethanone (1 mmol), o-aminothiophenol (1 mmol),
and KHSO4 (10 mol%) in CH3CN (5 mL) was refluxed. The reaction was monitored
by TLC. After completion, the reaction mixture was filtered. The filtrate was washed
twice with HCl (5%) and subsequently twice with NaHCO3 (5%). The organic layer
was dried, and the solvent was evaporated and recrystallized from ethyl acetate to
give the pure product (3).
Compound 3d
1
IR (KBr) (nmax, cmꢃ1): 2950, 2931, 1635, 1432, 1367, 756; HNMR (CDCl3,
300 MHz) dH (ppm): 3.02 (s, 2H), 3.57 (s, 3H), 7.04–7.591 (m, 8H, arom). GC=MS:
239 (Mþ).
ACKNOWLEDGMENT
The authors are thankful to the Alzahra Research Council for partial financial
support.
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