A convenient synthesis of 2-(1 H- 1,2,4-triazol-1-yl)-2H-1, 4-benzothiazine derivatives

Article abstract of DOI:10.1002/hc.20434

A series of 2-(1H-1,2,4-triaZol-1-yl)-2H-1, 4-benzothiazines were designed and synthesized by condensation of 1,2,4-triazole-substituted ω-bromoacetophenones and o-aminothiophenols with the aid of K ₂CO₃ under mild conditions with moderate to high yields.

Full text of DOI:10.1002/hc.20434

Heteroatom Chemistry
Volume 19, Number 3, 2008
Short Communication
A Convenient Synthesis of 2-(1H-1,2,4-
Triazol-1-yl)-2H-1,4-benzothiazine Derivatives
Weihui Zhong, Xiuling Sun, and Weike Su
Zhejiang Key Laboratory of Pharmaceutical Engineering, College of Pharmaceutical Sciences,
Zhejiang University of Technology, Hangzhou 310032, People’s Republic of China
Received 15 July 2007; revised 15 September 2007
zothiazoles or benzothiazolines [6], by the reac-
ABSTRACT: A series of 2-(1H-1,2,4-triazol-1-yl)-
tion of o-nitrobenzenesulfenyl chlorides with ke-
2H-1,4-benzothiazines were designed and synthe-
tones in the presence of HCl [7], by the treatment of
sized by condensation of 1,2,4-triazole-substituted ω-
aminothioalkenols with TsOH or H3PO4[8], by us-
bromoacetophenones and o-aminothiophenols with
ing 3H-1,2,3-benzodithiazole-2-oxides as synthons
the aid of K2CO3 under mild conditions with mod-
or by the reaction of bis(o-aminophenyl)disulfide
ꢀ
C
erate to high yields.
2008 Wiley Periodicals, Inc.
with ketones [9], by the reaction of bis(o-
nitrophenyl)disulfide with ω-bromoacetophenones
promoted by samarium di-iodide [10,11], by
condensation of ω-bromoacetophenones and o-
aminothiophenols in the presence of sodium in
ethanol [12]. Most of above-mentioned methods
involve harsh conditions such as strong acidic or
basic catalysts, special reagents, as well as long
reaction time. To the best of our knowledge, al-
though many methods have been introduced for the
preparation of 2H-1,4-benzothiazine derivatives or
triazole derivatives, the synthesis of a heterocyclic
compound that contains both 2H-1,4-benzothiazine
moiety and 1,2,4-triazole active group with a poten-
tial biological activity has not been reported.
Here, we report a simple and convenient method
for the preparation of 2-(1H-1,2,4-triazol-1-yl)-2H-
1,4-benzothiazine derivatives by condensation of
1,2,4-triazole-substituted ω-bromoacetophenones
and o-aminothiophenols with the aid of K2CO3
in aqueous EtOH media. The desired compounds
could be obtained under mild conditions with
moderate to high yields.
Heteroatom Chem 19:332–336, 2008; Published online
in Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.20434
INTRODUCTION
Heterocycles containing sulfur and nitrogen are bi-
ologically and industrially important compounds.
2H-1,4-Benzothiazine derivatives have attracted
much interest in modern society due to their bi-
ological properties [1]. On the other hand, 1,2,4-
triazole derivatives are one of the most widely used
fungicides due to their high efficiency, low toxicity,
and absorbent properties [2–4]. For example, 2H-
1,4-benzothiazine derivatives can be used as central
nervous system depressants, ataractic agents, anti-
spasmodics, and ciliary relaxants for pseudomyopia
and eye fatigue [5]. Many methods have been intro-
duced for the preparation of 2H-1,4-benzothiazine
derivatives, for example, by ring expansion of ben-
Correspondence to: Weike Su; e-mail: suweike@zjut.edu.cn.
Contract grant sponsor: National Basic Research Program of
China (973 Program).
Contract grant number: 2003CB114400.
Contract grant sponsor: National Natural Science Foundation
of China.
RESULTS AND DISCUSSION
Our first attempt was carried out by using 1H-1,2,4-
triazol-1-yl acetophenone 1a as a model substrate
Contract grant numbers: 20476098 and 20676123.
c
ꢀ
2008 Wiley Periodicals, Inc.
332

Convenient Synthesis of 2-(1H-1,2,4-Triazol-1-yl)-2H-1,4-benzothiazine Derivatives 333
SCHEME 1
SCHEME 2
(Scheme 1). The compound 1a was prepared accord-
ing to the method described in [13]. When 1a was
treated with 1.1 equivalent bromine in a solution of
AcOH at room temperature for about 30 min, the
color of solution was changed from red to colorless
and the intermediate 2a could be isolated, which re-
acted with o-aminothiophenol 3a in the presence of
various bases to afford the corresponding product 2-
(1H-1,2,4-triazol-1-yl)-2H-1,4-benzothiazine 4a and
such as Et3N, K2CO3, and NaOEt, were tested, and
it is evident from Table 1 that K2CO3 is a cheaper
and more efficient base for this reaction (entry 7).
However, when using Lewis acid (ZnCl2, LiClO4, or
AcOH) as a catalyst in ethanol, only a trace product
was detected even at high temperature or prolonging
reaction time (entries 10–13). So, we chose K2CO3
as a base and ethanol as a reaction solvent for this
reaction.
After the reaction condition was optimized,
we explored the reaction with various 1,2,4-
triazole-substituted ω-bromoacetophenones 2 and
o-aminothiophenols 3 (Scheme 2). The results are
summarized in Table 2.
According to Table 2, it was found that the
substrates with electron-donating groups (entry 4)
provided higher yields than those with electron with-
drawing groups on the aromatic ring (entry 13), but
it is not confirmed. Moreover, when R is an alkyl
group such as tert-butyl, the corresponding product
4n can also be obtained with moderate yield.
1
its structure was confirmed by H NMR, 13C NMR,
IR, mass spectra, and elemental analysis.
The cyclization of compound 3a with 2a is the
key step during the preparation of product 4a, so
influence of solvents and catalysts was investigated
in our experiment and the results are summarized
in Table 1. First, some solvents, such as acetone,
acetonitrile, and ethanol, were used for this reac-
tion. Acetone lessened the yield because it can re-
act with o-aminothiophenol 3a to afford the byprod-
uct 2,2-dimethyl-2,3-dihydrobenzo[d]thiazole (entry
1), whereas ethanol was proved to be efficient and
gave a good yield at room temperature (entry 3).
Increasing the reaction temperature did not change
the yield evidently (entry 4). Second, some bases,
TABLE 2 Preparation of 2-(1H-1,2,4-Triazol-1-yl)-2H-1,4-
benzothiazine Derivatives
Producta
TABLE 1 Preparation of 4a under Different Conditions
Entry
R
X
t (h) T ( ◦C) Yield (%)
Entry
Base
Solvent
T ( ◦C)
Yield (%)a
1
2
3
4
5
6
7
8
C6H5
H
H
H
H
H
H
H
Cl
Cl
1.5
1.0
1.0
0.5
0.5
2.0
2.0
1.5
1.0
1.0
0.5
2.0
2.0
2.0
r.t.
r.t.
r.t.
r.t.
60
60
60
r.t.
r.t
4a (67)
4b (68)
4c (66)
4d (70)
4e (65)
4f (45)
4g (43)
4h (50)
4i (62)
4j (68)
4k (66)
4l (64)
4m (58)
4n (65)
1
2
3
Et3N
Et3N
Et3N
Acetone
CH3CN
EtOH
60
60
r.t.
37
43
65
p-MeC6H4
o-MeOC6H4
2,4-(MeO)2C6H3
9H-Flurenyl
2-Furyl
p-ClC6H4
C6H5
p-MeC6H4
2,4-(MeO)2C6H3 Cl
9H-Flurenyl
2-Furyl
m-NO2C6H4
t-Butyl
4
5
6
7
8
9
10
11
12
13
Et3N
EtOH
60
60
60
r.t.
60
r.t.
66
38
46
67
68
67
Trace
Trace
Trace
Trace
K2CO3
K2CO3
K2CO3
K2CO3
NaOEt
DABCO
AcOH
ZnCl2
LiClO4
Acetone
CH3CN
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
9
10
11
12
13
14
r.t
r.t. or 60
r.t. or 60
r.t. or 60
r.t. or 60
Cl
Cl
Cl
Cl
60
60
60
r.t.
aIsolated yields based on compounds 1a.
aIsolated yields based on compounds 1.
Heteroatom Chemistry DOI 10.1002/hc

334 Zhong, Sun, and Su
In conclusion, we developed an efficient
and comparatively inexpensive methodology
for the synthesis of 2-(1H-1,2,4-triazol-1-yl)-2H-
1,4-benzothiazines by condensation of 1,2,4-
triazole-substituted ω-bromoacetophenones and
o-aminothiophenols. The advantages of the present
method are simple operation, mild reaction condi-
tion, and high yields.
reaction was monitored by TLC. Then, the reaction
mixture was filtered and the filtrate was evaporated
under reduced pressure. The crude product was
purified by column chromatography on silica gel
(100–200 mesh) with petroleum ether–ethyl acetate
(2:1 v/v) as an eluent to give the title compounds 4.
DATA OF PRODUCTS
3-Phenyl-2-(1H-1,2,4-triazol-1-yl)-2H-
benzo[b][1,4]thiazine (4a)
EXPERIMENTAL
Instruments and Reagents
Light-yellow crystals, mp 56.8–57.3◦C; IR (KBr), νmax
:
1
All reagents were commercially available and were
used without purification. Compounds 1 were pre-
pared according to the method described in [12].
Infrared spectra were recorded on a Thermo Nico-
2990, 1639, 1622, 765 cm−1; H NMR (CDCl3), δH:
6.76 (1H, s, CH), 7.25–7.28 (1H, m, Ar-H), 7.34–7.41
(2H, m, Ar-H), 7.48–7.53 (3H, m, Ar-H), 7.65 (1H, s,
triazole-H), 7.73 (1H, d, J = 8.0 Hz, Ar-H), 7.92 (1H,
s, triazole-H), 8.06 (2H, d, J = 8.0 Hz, Ar-H); 13C
NMR (100 Hz, CDCl3), δ: 50.3, 117.2, 127.4, 127.6,
128.0, 128.4, 128.9, 129.2, 129.6, 131.5, 135.7, 140.8,
142.4, 149.4, 152.1, 162.4; m/z (%): 292 (M+, 2.0),
223 (3.0), 211 (100). Anal. Calcd for C16H12N4S: C,
65.73; H, 4.14; N, 19.16. Found: C, 65.69; H, 4.08; N,
19.20.
let Avatar 370 spectrophotometer. H NMR and13C
1
NMR spectra were measured on a Varian Mercury
plus-400 spectrometer with tetramethylsilane (TMS)
as an internal standard and CDCl3 as the solvent.
Mass spectra were obtained with a Thermo Finni-
gan LCQ-Advantage (EI). Elemental analyses were
carried out on a Vario EL III instrument. High-
resolution mass spectral (HRMS) analyses were
measured on an APEX (Bruker) mass III spectrom-
eter using ESI (electrospray ionization) techniques.
3-p-Tolyl-2-(1H-1,2,4-triazol-1-yl)-2H-
benzo[b][1,4]thiazine (4b)
Light-yellow crystals, mp 62.5–63.1◦C; IR (KBr) νmax
:
General Procedure for the Preparation of
2-Bromo-1-phenyl-2-(1H-1,2,4-triazol-1-
yl)ethanone 2
3010, 2896, 1610, 1590, 1475, 1380, 760 cm−1; H
NMR (400 Hz, CDCl3), δH: 2.40 (3H, s, CH3), 6.75 (1H,
s, CH), 7.23–7.37 (5H, m, Ar-H), 7.64 (1H, s, triazole-
H), 7.70 (1H, d, J = 8.4 Hz, Ar-H), 7.90 (1H, s,
triazole-H), 7.95 (2H, d, J = 8.0 Hz, Ar-H); 13C NMR
(100 Hz, CDCl3) δ: 21.4, 50.4, 117.2, 127.5, 127.6,
127.7, 128.3, 129.1, 129.3, 129.7, 132.9, 140.9, 141.0,
142.3, 142.5, 149.4, 152.2; m/z (%): 306(M+, 16.9),
237 (100), 225 (82.0). Anal. Calcd for C17H14N4S: C,
66.64; H, 4.61; N, 18.29. Found: C, 66.75; H, 4.52; N,
18.33.
1
To a mixture of 1-aryl-2-(1H-1,2,4-triazol-1-yl)-
ethanone 1 (2.0 mmol) and sodium acetate (0.16 g,
2.0 mmol) in acetic acid (5 mL), a solution of
bromine (0.32 g, 2.0 mmol) in acetic acid (1 mL)
at 15◦C was added slowly. The mixture was stirred
at room temperature until the color of solution be-
came colorless from red. The reaction was quenched
with ice water and was extracted with chloroform
(15 mL). The organic phase was washed with brine
and dried over anhydrous Na2SO4. After evaporating
under reduced pressure, the crude product 2-bromo-
1-aryl-2-(1H-1,2,4-triazol-1-yl)ethanone 2 was ob-
tained and was used for the next step.
3-(2-Methoxyphenyl)-2-(1H-1,2,4-triazol-1-yl)-
2H-benzo[b][1,4]thiazine (4c)
Light-yellow crystals, mp 56.8–57.3◦C; IR (KBr) νmax
:
1
3100, 2983, 1620, 1585, 1465, 1250 cm−1; H NMR
(400 Hz, CDCl3) δH: 3.69 (3H, s, OCH3), 6.69 (1H,
s, CH), 6.83 (1H, d, J = 8.8 Hz, Ar-H), 7.22–7.27
(2H, m, Ar-H), 7.32–7.39 (2H, m, Ar-H), 7.55 (1H,
dd, J = 8.8 Hz and J = 2.8 Hz, Ar-H), 7.63 (1H,
s, triazole-H), 7.72–7.74 (1H, m, Ar-H), 7.87 (1H, s,
triazole-H), 7.98 (1H, d, J = 2.8 Hz, Ar-H); 13C NMR
(100 Hz, CDCl3), δ: 51.8, 56.0, 113.1, 113.8, 118.4,
127.6, 127.7, 128.0, 128.6, 129.0, 134.2, 135.2, 141.2,
142.8, 148.9, 152.0, 157.0; m/z (%): 322 (M+, 2.0), 253
General Procedure for the Preparation of
3-Aryl-2-(1H-1,2,4-triazol-1-yl)-2H-
benzo[b][1,4]thiazine 4
A
mixture of the crude product 2-bromo-
1-aryl-2-(1H-1,2,4-triazol-1-yl)ethanone 2, o-
aminothiophenol (2.0 mmol), and K2CO3 (1.0
mmol) in EtOH (10 mL) was stirred at room
temperature or 60◦C at a given time (Table 1). The
Heteroatom Chemistry DOI 10.1002/hc

Convenient Synthesis of 2-(1H-1,2,4-Triazol-1-yl)-2H-1,4-benzothiazine Derivatives 335
(1.0), 83(100). Anal. Calcd for C17H14N4OS: C, 63.33;
H, 4.38; N, 17.38. Found: C, 63.17; H, 4.23; N, 17.44.
3-(4-Chlorophenyl)-2-(1H-1,2,4-triazol-1-yl)-2H-
benzo[b][1,4]thiazine (4g)
Light-yellow crystals, mp 61.8–62.6◦C; IR (KBr) νmax
2935, 1655, 1645, 1090, 755 cm−1; 1H NMR (400
Hz, CDCl3) δH: 6.70 (1H, s, CH), 7.26–7.29 (1H, m,
Ar-H), 7.34–7.40 (2H, m, Ar-H), 7.45 (2H, d, J =
8.4 Hz, Ar-H), 7.65 (1H, s, triazole-H), 7.70 (1H,
d, J = 8.0 Hz, Ar-H), 7.90 (1H, s, triazole-H), 8.02
(2H, d, J = 8.8 Hz, Ar-H);13C NMR (CDCl3), δ: 50.3,
117.2, 127.7, 127.9, 128.8, 128.9, 129.2, 129.3, 129.4,
129.5, 134.3, 138.0, 140.8, 142.5, 148.5, 152.3; m/z
(%): 328(M+ + 2, 5.5), 326(M+, 15.0), 258 (80.0), 245
(100). Anal. Calcd for C16H11ClN4S: C, 58.80; H, 3.39;
N, 17.14. Found: C, 58.88; H, 3.33; N, 17.01.
:
3-(2,5-Dimethoxyphenyl)-2-(1H-1,2,4-triazol-1-
yl)-2H-benzo[b][1,4]thiazine (4d)
Light-yellow crystals, mp 66.2–66.7◦C; IR (KBr) νmax
:
1
3093, 2985, 1625, 1580, 1465, 1252 cm−1; H NMR
(400 Hz, CDCl3) δH: 3.64 (3H, s, OCH3), 3.82 (3H, s,
OCH3), 6.76 (1H, s, CH), 6.88 (1H, d, J = 9.2 Hz,
Ar-H), 7.03 (1H, dd, J = 8.8 Hz and J = 3.0 Hz,
Ar-H), 7.20–7.27 (1H, m, Ar-H), 7.32–7.37 (2H, m,
Ar-H), 7.42 (1H, d, J = 2.8 Hz, Ar-H), 7.66 (1H, s,
triazole-H), 7.73 (1H, d, J = 8.0 Hz, Ar-H), 7.87 (1H,
s, triazole-H); 13C NMR (100 Hz, CDCl3), δ: 52.0, 55.8,
56.1, 112.7, 115.6, 118.4, 119.1, 126.1, 127.5, 127.9,
128.2, 128.7, 141.4, 142.9, 150.2, 151.9, 152.4, 153.9;
m/z (%) : 352 (M+, 3.0), 271 (62.0), 238 (100). Anal.
Calcd for C18H16N4O2S: C, 61.35; H, 4.58; N, 15.90.
Found: C, 61.29; H, 4.38; N, 16.12.
6-Chloro-3-phenyl-2-(1H-1,2,4-triazol-1-yl)-2H-
benzo [b] [1,4]
thiazine (4h)
Light-yellow crystals, mp 72.5–73.3◦C; IR (KBr) νmax
:
2940, 1639, 1622, 763 cm−1; 1H NMR (400 Hz, CDCl3)
δH: 6.78 (1H, s, CH), 7.23–7.29 (3H, m, Ar-H), 7.48–
7.56 (3H, m, Ar-H), 7.68 (1H, s, triazole-H), 7.74 (1H,
d, J = 1.6 Hz, Ar-H), 7.93 (1H, s, triazole-H), 8.06
(1H, d, J = 7.6 Hz, Ar-H);13C NMR(CDCl3), δ: 50.3,
115.8, 127.7, 128.6, 129.0, 129.1, 132.1, 133.2, 135.4,
137.1, 138.5, 140.6, 141.8, 142.5, 150.7, 152.5; m/z
(%): 328 (M+ + 2, 5.5), 326 (M+, 15.0), 258 (80.0),
245 (100); Anal. Calcd for C16H11ClN4S: C, 58.80; H,
3.39; N, 17.14. Found: C, 58.66; H, 3.26; N, 17.21.
3-(9H-Fluoren-2-yl)-2-(1H-1,2,4-triazol-1-yl)-
2H-benzo[b][1,4]thiazine (4e)
Light-yellow crystals, mp 106.4–107.9◦C; IR (KBr),
1
νmax: 3110, 2856, 1615, 1580, 1475, 1255 cm−1; H
NMR (400 Hz, CDCl3) δH: 3.94 (2H, s, CH2), 6.82
(1H, s, CH), 7.24–7.26 (1H, m, Ar-H), 7.33–7.40 (4H,
m, Ar-H), 7.56 (1H, d, J = 7.2 Hz, Ar-H), 7.69 (1H, s,
Ar-H), 7.74 (1H, d, J = 7.6 Hz, Ar-H), 7.82(2H, t, J
= 7.2 Hz, Ar-H), 7.94 (1H, s, triazole-H), 8.05 (1H, d,
J = 8.0 Hz, Ar-H), 8.26 (1H, s, triazole-H); 13C NMR
(100 Hz, CDCl3), δ: 36.9, 53.8, 117.3, 120.2, 120.7,
124.2, 125.2, 126.7, 127.0, 127.4, 127.8, 127.9, 128.3,
129.2, 134.1, 140.5, 141.2, 142.6, 143.9, 144.2, 145.3,
149.9, 152.3; m/z (%): 380 (M+, 18.0), 312 (16.0), 299
(100). Anal. Calcd for C23H16N4S: C, 72.61; H, 4.24;
N, 14.73. Found: C, 72.46; H, 4.09; N, 14.91.
6-Chloro-3-p-tolyl-2-(1H-1,2,4-triazol-1-yl)-2H-
benzo[b][1,4]thiazine (4i)
Yellow crystals, mp 76.8–77.5◦C; IR (KBr) νmax: 3116,
3019, 1635, 1612, 1215, 756 cm−1; 1H NMR (400 Hz,
CDCl3) δH: 2.39 (3H, s, CH3), 6.78 (1H, s, CH), 7.23–
7.37 (5H, m, Ar-H), 7.67 (1H, s, triazole-H), 7.70 (1H,
d, J = 8.4 Hz, Ar-H), 7.89 (1H, s, triazole-H), 7.95
(1H, d, J = 8.0 Hz, Ar-H); 13C NMR (100 Hz, CDCl3),
δ: 21.4, 50.1, 115.7, 127.6, 127.6, 128.1, 128.4, 128.7,
129.7, 129.7, 132.5, 133.0, 141.8, 142.4, 142.8, 150.5,
152.3; m/z (%): 342 (M+ + 2, 32.0), 340 (M+, 86.9),
271 (100), 259 (54.0). Anal. Calcd for C17H13ClN4S:
C, 59.91; H, 3.84; N, 16.44. Found: C, 59.78; H, 3.76;
N, 16.62.
3-(Furan-2-yl)-2-(1H-1,2,4-triazol-1-yl)-2H-
benzo[b][1,4]thiazine (4f)
Oil, IR (neat) νmax: 3050, 1615, 1570, 1455, 1250
1
cm−1; H NMR (400 Hz, CDCl3) δH: 6.61–6.62 (1H,
m, Ar-H), 6.71 (1H, s, CH), 7.23–7.39 (4H, m, Ar-
H), 7.65–7.70 (2H, m, Ar-H), 7.73 (1H, s, triazole-H),
7.87 (1H, s, triazole-H); 13C NMR (100 Hz, CDCl3), δ:
49.5, 113.0, 115.2, 117.6, 127.8, 128.3, 128.3, 129.1,
140.7, 141.0, 142.3, 146.3, 150.3, 152.1; m/z (%): 282
(M+, 72.2), 253 (62.5), 214 (100), 201 (53.1), 186
(24.0). HRMS (ESI) Calcd for C14H10N4OS (M + H)+,
283.0575. Found: (M + H)+, 283.0571.
6-Chloro-3-(2,5-dimethoxyphenyl)-2-(1H-1,2,4-
triazol-1-yl)-2H-benzo[b][1,4]thiazine (4j)
Light-yellow crystals, mp 78.3–78.9◦C; IR (KBr) νmax
:
1
3063, 2925, 1620, 1570, 1450, 1252 cm−1; H NMR
(400 Hz, CDCl3) δH: 3.64 (3H, s, OCH3), 3.82 (3H, s,
OCH3), 6.82 (1H, s, CH), 6.88 (1H, d, J = 8.8 Hz,
Heteroatom Chemistry DOI 10.1002/hc

336 Zhong, Sun, and Su
δ: 50.0, 115.9, 122.9, 126.1, 128.4, 129.3, 129.4,
130.2, 133.2, 133.5, 137.3, 141.3, 142.4, 148.5, 148.8,
152.6; m/z (%):373 (M+ + 2, 15.0), 371 (M+, 43.0),
302 (100), 290 (20.5), 257 (36.5). Anal. Calcd for
C16H10ClN5O2S: C, 51.69; H, 2.71; N, 18.84. Found:
C, 51.72; H, 2.59; N, 18.77.
Ar-H), 7.03 (1H, dd, J = 8.8 Hz and J = 2.8 Hz,
Ar-H), 7.18–7.27 (2H, m, Ar-H), 7.42 (1H, d, J = 7.6
Hz, Ar-H), 7.69(1H, s, triazole-H), 7.74 (1H, d, J =
2.4, Ar-H), 7.87 (1H, s, triazole-H); 13C NMR (100 Hz,
CDCl3), δ: 51.7, 55.7, 56.0, 112.8, 115.6, 116.9, 119.5,
125.7, 128.0, 128.3, 128.6, 132.8, 142.2, 142.8, 151.2,
152.0, 152,5, 153.9; m/z (%): 388(M+ + 2, 5.0), 386
(M+, 16.0), 305 (41.5), 272 (100), 170 (87.1). Anal.
Calcd for C18H15ClN4O2S: C, 55.88; H, 3.91; N, 14.48.
Found: C, 55.81; H, 3.95; N, 14.62.
6-Chloro-3-(t-butyl)-2-(1H-1,2,4-triazol-1-yl)-
2H-benzo[b][1,4]thiazine (4n)
Oil, IR (neat) νmax: 3052, 2930, 2840, 1621, 1560,
1091 cm−1; H NMR (400 Hz, CDCl3) δH: 1.17 (9H,
1
6-Chloro-3-(9H-fluoren-2-yl)-2-(1H-1,2,4-
triazol-1-yl)-2H-benzo[b][1,4]thiazine (4k)
s, CH3), 6.37 (1H, s, CH), 7.20–7.50 (3H, m, Ar-H),
7.87 (1H, s, triazole-H), 8.03 (1H, s, triazole-H); 13C
NMR (100 Hz, CDCl3), δ 26.5, 26.5, 26.5, 40.7, 48.1,
116.1, 127.8, 128.0, 128.7, 132.8, 141.2, 142.5, 152.3,
163.6; m/z(%): 308 (M+ + 2, 3.5), 306 (M+, 11.0), 240
(7.0), 226 (10.0), 57 (100). HRMS (ESI) calcd for
C14H15ClN4S (M + H)+, 307.0706, Found: (M + H)+,
307.0703.
Light-yellow crystals, mp 131.8–133.0◦C; IR (KBr)
νmax: 3017, 2927, 1639, 1612, 1216, 1091, 756 cm−1;
1H NMR (400 Hz, CDCl3) δH: 3.91 (2H, s, CH2), 6.84
(1H, s, CH), 7.18–7.25 (2H, m, Ar-H), 7.34–7.41 (2H,
m, Ar-H), 7.55 (1H, d, J = 6.0 Hz, Ar-H), 7.71–7.81
(4H, m, Ar-H), 7.93 (1H, s, triazole-H), 8.03 (1H, t,
J = 7.6 Hz, Ar-H), 8.23 (1H, s, triazole-H); 13C NMR
(100 Hz, CDCl3), δ 36.8, 50.4, 115.7, 120.1, 120.7,
124.3, 125.1, 126.8, 127.0, 128.0, 128.2, 128.5, 128.7,
133.1, 133.5, 140.3, 142.0, 142.5, 143.9, 144.2, 145.7,
150.8, 152.4; m/z (%): 416(M+ + 2, 2.0), 414(M+, 7.0),
347 (25.0), 333 (100). Anal. Calcd for C23H15ClN4S:
C, 66.58; H, 3.64; N, 13.50. Found: C, 66.45; H, 3.60;
N, 13.59.
REFERENCES
[1] Brown, C.; Davidson, R. M. Heterocycl Chem 1985,
38, 135.
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Eur J Med Chem 2007, 42, 521.
[3] Liu, J. B.; Tao, W. F.; Dai, H.; Jin, Z. and Fang, J. X.
Heteroatom Chem 2007, 18(4), 376.
[4] Cartarzi, D.; Colotta, V.; Varono, F.; Cecchi, L.;
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Chem 2000, 43, 3824.
6-Chloro-3-(furan-2-yl)-2-(1H-1,2,4-triazol-1-yl)-
2H-benzo [b][1,4]thiazine (4l)
[5] (a) Krapcho, J.; Yale, H. L. US3,117,124; Chem Abstr
1964, 60: 8049a; (b) Shirasawa, E.; Kageyama, M.
JP07133225; Chem Abstr 1995, 123: p123157x.
[6] (a) Hori, M.; Kataoka, T.; Shimizu, H.; Ueda, N.
Tetrahedron Lett 1981, 22, 1701; (b) Trapani, G.;
Reho, A.; Latrofa, A.; Morlacchi, F.; Liso, G. J Chem
Res (S) 1986, 961; (c) Finar, I. L.; Monugomery, A. J.
J Chem Soc 1961, 367.
[7] Sauleau, A.; David, M.; Sauleau, J. Synth Commun
1998, 28, 4105.
[8] Sawhney, S. N.; Sharma, P. K.; Bajaj, K. Indian J
Chem Sect B 1994, 33, 280.
[9] (a) Chang, Y.; Peak, J. D.; Wierschke, S. W.; Feld,
W. A. Synth Commun 1993, 23, 663; (b) Carelli, V.;
Marchini, P.; Micheletti-Moeacci, F.; Liso, G. Tetra-
hedron Lett 1967, 7, 34. (c) Trapani, G.; Latrofa, A.;
Reho, A.; Liso, G. J Heterocycl Chem 1989, 26, 721.
[10] Zhang, Y. M.; Zhong, W. H.; Chen, X. Y. Heteroatom
Chem 2001, 12(3), 156.
Oil, IR (neat) νmax: 3030, 1610, 1560, 1455, 1250
1
cm−1; H NMR (400 Hz, CDCl3) δH: 6.63–6.64 (1H,
m, Ar-H), 6.73 (1H, s, CH), 7.21–7.34 (3H, m, Ar-
H), 7.66–7.70 (2H, m, Ar-H), 7.77 (1H, s, triazole-H),
7.87 (1H, s, triazole-H); 13C NMR (100 Hz, CDCl3), δ:
49.4, 113.4, 116.0, 126.4, 128.3, 128.6, 129.7, 133.3,
141.6, 141.8, 142.3, 146.7, 150.1, 152.5; m/z (%): 318
(M+ + 2, 29.5), 316 (M+, 91), 287 (86.0), 248 (100),
235 (58.0). HRMS (ESI) Calcd for C14H9ClN4OS
(M + H)+, 317.0186. Found: (M + H)+, 317.0188.
6-Chloro-3-(3-nitrophenyl)-2-(1H-1,2,4-triazol-
1-yl)-2H-benzo[b][1,4]thiazine (4m)
Light-yellow crystals, mp 116.7–117.8◦C; IR (KBr)
[11] Zhang, Y. M.; Zhong, W. H.; Chen, X. Y. Chin J Chem
2001, 19(2), 189.
[12] MacKenzie, N. E.; Thomson, R. H.; Greenhalgh,
C. W. J Chem Soc, Perkin Trans 1 1980, 2923–2932.
[13] Maryanoff, B. E.; Keeley, S. L.; Persico, F. J. J Med
Chem 1983, 26, 226.
νmax: 3087, 1641, 1612, 1568, 1532, 1350, 1215, 1091,
1
756 cm−1; H NMR (400 Hz, CDCl3) δH: 6.85 (1H, s,
CH), 7.29–7.36 (2H, m, Ar-H), 7.68–7.83 (3H, m, Ar-
H), 7.88 (1H, s, triazole-H), 8.35–8.43 (2H, m, Ar-H),
8.97 (1H, s, triazole-H); 13C NMR (100 Hz, CDCl3),
Heteroatom Chemistry DOI 10.1002/hc