Yield of benzothiazine derivatives and catalysis by heteropolyacids

Article abstract of DOI:10.1080/17415993.2016.1187733

An efficient heteropolyacid-catalyzed reaction for the synthesis of benzothiazine derivatives is reported. In this transformation, H₃PW₁₂O₄₀ was employed as a catalyst in a reaction involving 2-aminobenzenethiols, acetylenic esters, and malonate esters. Optimum conditions are developed in i-PrOH at 50?C for 7 h.

Full text of DOI:10.1080/17415993.2016.1187733

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Yield of benzothiazine derivatives and catalysis by
heteropolyacids
Alireza Samzadeh-Kermani
To cite this article: Alireza Samzadeh-Kermani (2016): Yield of benzothiazine
derivatives and catalysis by heteropolyacids, Journal of Sulfur Chemistry, DOI:
10.1080/17415993.2016.1187733
To link to this article: http://dx.doi.org/10.1080/17415993.2016.1187733
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Date: 04 June 2016, At: 02:02

JOURNAL OF SULFUR CHEMISTRY, 2016
http://dx.doi.org/10.1080/17415993.2016.1187733
Yield of benzothiazine derivatives and catalysis by
heteropolyacids
Alireza Samzadeh-Kermani
Department of Chemistry, Faculty of Science, University of Zabol, Zabol, Iran
ABSTRACT
ARTICLE HISTORY
Received 5 January 2016
Accepted 27 April 2016
An efficient heteropolyacid-catalyzed reaction for the synthesis
of benzothiazine derivatives is reported. In this transformation,
H3PW12O40 was employed as a catalyst in a reaction involving 2-
aminobenzenethiols, acetylenic esters, and malonate esters. Opti-
mum conditions are developed in i-PrOH at 50˚C for 7 h.
KEYWORDS
Heteropolyacid;
multicomponent reaction;
heterogeneous catalyst; 1;
4-benzothiazine;
heterocycles
1. Introduction
Multicomponent reactions (MCR) are efficient methods in diversity-oriented synthesis of
heterocycles.[1–3] Among the various types of MCR, reactions promoted by catalysts have
served as powerful tools for the rapid and efficient syntheses of highly demanding hete-
rocyclic compounds.[4,5] In particular, heteropolyacids (HPAs)-catalyzed reactions have
gained considerable interest for the synthesis of heterocyclic compounds.[6] Among the
heterocycles, 1,4-benzothiazine derivatives possess numerous biological activities such as
antibiotic, anticancer, antiviral, antifungal, antimicrobial, antiarrhythmic, and anti HIV
antiallergic.[7,8] 1,4-Benzothiazine structures are typically synthesized by cycloconden-
sation of 2-aminobenzothiazole with α, β-unsaturated acids or esters, electron deficient
alkynes; cyclocondensations of 2-aminobenzothiaoles with α-haloketones; condensation
and oxidative cyclization of N-unsubstituted and N,N-dialkyldithioanilines with 1,3-
dicarbonyls or esters; ring expansions of benzothiazolines by using different oxidants such
as iodine and sulfuryl chloride.[7,9–13] Yavari and coworkers have reported a novel route
for the synthesis of benzoxazine and quinioxaline derivatives in a reaction involving 2-
aminophenols or 1,2-benzene diamine, acetylenic esters, and malonyl chloride. While the
importance of this reaction cannot be overstated, the main drawbacks of this protocol are
using malonyl chloride and chlorinated solvent. As part of our ongoing research toward
heterocycles syntheses,[14–17] we report a simple and greener protocol for the preparation
CONTACT Alireza Samzadeh-Kermani
drsamzadeh@gmail.com
© 2016 Informa UK Limited, trading as Taylor & Francis Group

2
A. SAMZADEH-KERMANI
Scheme 1. Synthesis of 1,4-benzothiazine derivatives.
of the 1,4-benzothiazine skeletons from readily available 2-aminobenzenethiols, acetylenic
esters, and malonate esters catalytic in HPAs (Scheme 1).
2. Results and discussion
The catalytic reaction was initially examined (2-aminobenzenethiol (1a), dimethyl
acetylenedicarboxylate (2a, DMAD), and dimethyl malonate (3a)) in the presence of
H4PMo12O40 as a model reaction to assess the reaction efficiency. Stirring in toluene at
50°C for 4 h gave 4a in 11% yield. To develop the reaction conditions, a variety of cat-
alysts and solvents were examined (Table 1). No desired product formation took place
in the absence of a HPA source even at higher temperatures and for longer reaction
times, and methyl-2-(3-oxo-3,4-dihydro-2H-benzo[b][1,4]thiazin-2-ylidene)acetate was
obtained (5) in 93% yield instead (Table 1, Entry 14). This result supports the suggested
mechanism pathway. The influence of the different metals on the HPAs efficiency was then
examined (Table 1, Entries 1–5). The study indicated that HPAs with tungsten as central
atom resulted in comparatively higher yields than those composed of molybdenum, which
is most likely due to the greater acidity of W-containing HPA.[18] A modest decrease in
yield occurred using Cs salt of HPA (Table 1, Entry 6). Supported H3PW12O40 on con-
ventional amorphous silica required longer reaction times to give the desired product in
comparable yields (Figure 1 and Table 1, Entry 7). It is worth mentioning that silica mate-
rials alone as the catalyst did not promote the desired product formation (not shown in
Table 1).
Reactions conducted in alcoholic solvents resulted in high conversions (Table 1, Entries
2, 7–8). Reaction in polar-aprotic solvents occurred to lower conversions, likely due to the
leaching of catalyst (Table 1, Entries 9–10). Reaction conducted in an etheric solvent such
as THF occurred to low conversion (Table 1, Entry 12). It is worth mentioning that the
desired product obtained only in 22% yield when deionized water was used as the solvent
(Table 1, Entry 13). The study indicated that the presence of the catalyst was necessary to
form the desired product (Table1, Entry 14). Finally, a catalyst loading screen indicated that
the yield remained almost unchanged by decreasing the catalyst amount to 60 mg; however,
the yield was observed to decrease as the catalyst amount reduced further (Table 1, Entries
15–16).
The optimum reaction conditions proved to be effective in the preparation of a
number of substituted 1,4-benzothiazines (Table 2). Electron-natural substrates 1a–1b
afforded the desired products in good yields (© 2016 Tom Stewart, Entries 1–2). 2-
aminobenzenethiol containing chloro group gave the corresponding product in compara-
tively lower yields (Table 2, Entries 3–4). The reactions conducted with methyl substituted
2-aminobenzenethiol proceeded in high conversion (Table 2, Entries 5–6). Reaction of

JOURNAL OF SULFUR CHEMISTRY
3
Figure 1. SEM of silica (left), SEM of supported HPA on silica (middle and right).
Table 1. Optimization of the reaction conditionsa.
Entry
Catalyst
Solvent
Yield (%)
1
2
3
4
5
6
7
8
H4SiW12O40
H3PW12O40
H4PMo12O40
H3PMo10W2O40
H4SiMo12O40
Cs2HPW12O40
H3PW12O40-Silica
H3PW12O40
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
i-PrOH
EtOH
50
86
48
62
37
.
39
84b
71
9
H3PW12O40
H3PW12O40
H3PW12O40
DMSO
DMF
Toluene
THF
traces
traces
23
10
11
12
13
14
15
16
H3PW12O40
H3PW12O40
–
,
,
13
22
H2O
i-PrOH
i-PrOH
i-PrOH
tracec
84d
70e
H3PW12O40-Silica
H3PW12O40-Silica
aFor all entries except stated otherwise: 1a (1.0 mmol), 2a (1.0 mmol), 3a (3.0 mmol), catalyst (0.1 mmol), solvent (3 mL),
50°C, 4 h.
bh, 100 mg supported catalyst.
c5 was obtained in 96% yield.
d7 h, 60 mg supported catalyst.
e7 h, 50 mg supported catalyst.
electron-rich aminobenzenethiol occurred to excellent conversion (Table 2, Entry 7). Sub-
strate containing bromo moiety was also tolerated. Notably, the tolerance for bromide
on the aromatic ring offers an opportunity for subsequent cross-coupling, facilitating
expedient synthesis of highly complex 1,4-bezoxthiazines (Table 2, Entry 8). This reac-
tion was sensitive to steric effects as 2-amino-6-(tert-butyl)benzenethiol did not give the
desired product (not shown in Table 2); however, 2-amino-4-(tert-butyl)benzenethiol (1i)

4
A. SAMZADEH-KERMANI
Table 2. Synthesis of 1,4-benzothiazine derivativesa.
Entry
Amine
R1
2
Malonate
R2
Yield (%)
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
1a
1a
1a
1a
1a
1a
1a
1a
1a
1a
H
C4H4
5-Cl
4-Cl
5-CH3
4-CH3
4-OCH3
4-Br
4-t-Bu
H
H
H
H
H
H
H
H
H
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2a
2a
2a
2a
2a
2a
2a
2a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3a
3b
3c
3d
3e
3f
Et, Et
Et, Et
Et, Et
Et, Et
Et, Et
Et, Et
Et, Et
Et, Et
Et, Et
4a, 89
4b, 92
4c, 85
4d, 82
4e, 89-
4f, 90
4g, 96
4h, 81
4i, 87
9
10
11
12
13
14
15
16
17
18
19
Et, Et
Et, Et
4j, 86
4k, 92
4a, 69
4a, 54
4a, 89
4a, 80
4a, 60
4a, 87d
4a, 80
4a, 67
Me, Me
Bn, Bn
i-Pr, i-Pr
t-Bu, t-Bu
H, H
Et, Et
Et, Et
Et, Et
3a
3a
3a
H
aFor all entries except stated otherwise: 1 (1.0 mmol), 2 (1.0 mmol), 3 (3.0 mmol), catalyst (60 mg), in i-PrOH (3 mL) at 50˚C
for 7 h.
b1.0 mmol of diethyl acetylenedicarboxylate (2b) was used.
cAt 100°C for 11 h.
dEntries 17–19 indicate the yield of the product in recycling tests, second through fourth runs.
afforded the desired product in acceptable yields (Table 2, Entry 9). The presence of
electron-withdrawing groups such as nitro or cyano on 2-aminobenzenethiol ring was
not compatible with this transformation. Diethyl and di-tert-butyl acetylenedicarboxy-
lates also afforded the corresponding 1,4-benzothiazine structures in good yields (Table 2,
Entries 10–11). Other malonate esters were also examined and gave the desired product
in acceptable yields; however, diethyl malonate (3a) was selected as the malonate of choice
based on the cost and efficiency (Table 2, Entries 12–15). Malonic acid (3f) gave the desired
product in competitively lower yield even at higher temperatures (Table 2, Entries 16).
The recyclability of the heterogeneous catalyst is one of the most important issues for
practical applications. For this reason, the recyclability of the catalyst was then examined
using the model reaction (Table 2, Entries 17–19). After the completion of the reaction, the
catalyst was recovered by filtration, followed by washing with ethanol (10 mL × 3). After
drying (80°C for 6 h in vacuo), the catalyst was reused directly for the next reaction. The
catalytic activity remained almost unchanged after three catalytic cycles, indicating that
the catalyst is stable and can be regenerated for repeated use. However, the yield decreased
when the catalyst was used for the fourth run.

JOURNAL OF SULFUR CHEMISTRY
5
Scheme 2. Proposed mechanism for the synthesis of 1,4-benzothiazine derivatives.
As reported in previous reports, compounds 5 and 6 are obtained by treating 1a and
2a.[19,20] Liso and coworkers have reported that the thiol group reacts first, in contrast
with results reported by Fomum, et al. When we treated 1a with 2a in the absence of the
catalyst, 5 was obtained in 96% yield (Table 1, Entry 14), which is in favor of Liso’s results.
However, the reaction conducted with 1a and 2a using SiO2@H3PW12O40 resulted in
formation of methyl-2-(2-oxo-2H-benzo[b][1,4]thiazin-3(4H)-ylidene)acetate (7) in 93%
yield, which indicates the reaction starts with the amine attack. It could be deduced that the
presence of catalyst is necessary to form the intermediate 8 and 9. We could not isolate the
intermediate 10 from the reaction mixture. Based on these findings, a tentative mechanism
for this transformation is proposed in Scheme 2. It is conceivable that the initial event is
the formation of intermediate 8, which is converted to alkylidene 9. This adduct is subse-
quently attacked by malonate ester to produce 10, followed by cyclization reaction, alcohol
elimination, and keto-enol tautomerism to generate the desired product.
In conclusion, we have described a green and efficient procedure for the synthesis of
1,4-benzothiazine derivatives. To our knowledge, this work was the first example of the uti-
lizing SiO2@HPAs as reusable catalyst for the synthesis of 1,4-benzothiazines in a reaction
involving 2-aminobenzenethiols, acetylenic esters, and dialkyl malonates. The optimized
reaction conditions reported herein are compatible with the presence of functional groups
such as OMe, Cl, Br, and t-Bu.
2.1. Experimental
All reagents were purchased from the Merck chemical companies and used without fur-
ther purification. Products were characterized by different spectroscopic methods (FT–IR,

6
A. SAMZADEH-KERMANI
GC-Mass, and 1H NMR spectra), elemental analysis (CHN), and melting points. The NMR
spectra were recorded in DMSO-d6. 1H NMR spectra were recorded on a Bruker Avance
DRX 500 MHz instrument. The chemical shifts (δ) are reported in ppm relative to the TMS
as internal standard. J values are given in Hz. IR (KBr) spectra were recorded on a Perkin-
Elmer 781 spectrophotometer. Melting points were taken in open capillary tubes with a
BUCHI 510 melting point apparatus and were uncorrected. The elemental analysis was per-
formed using Heraeus CHN-O-Rapid analyzer. TLC was performed on silica gel polygram
SIL G/UV 254 plates. Morphology and particle dispersion was investigated by scanning
electron microscopy (SEM) (Cam scan MV2300).
2.1.1. General procedure for the preparation of SiO2@H3PW12O40
The HPAs were prepared by a hydrothermal synthesis method.[21] As an example,
H4PMo12O40 was prepared according to the following procedure: A mixture of phos-
phoric acid (0.98 g) and of molybdenum trioxide (14.4 g) was suspended in distilled H2O
(150 mL) and the mixture stirred for 6 h at 80°C. After cooling to 20°C and removal of insol-
uble molybdates, the HPA solution was evaporated and dried at 85°C for 24 h to give orange
crystals. Silica-supported HPA was prepared by the standard literature procedure.[22] A
mixture of silica (DavisilTM, 200–425 mesh, 150) and HPA in H2O–i-PrOH or MeCN was
stirred at 25°C for 24 h. The catalyst was washed with deionized H2O and dried at 110°C
for 12 h. The supported catalyst was then calcinated at 200°C for 3 h.
2.1.2. Typical procedure for preparation of 4
A mixture of acetylenic ester (1.0 mmol) and 2-aminobenzenethiol (1.0 mmol) was stirred
at 0°C for 20 min. A solution of malonate source (3.0 mmol) and HPA (0.1 mmol or 100 mg
of supported HPA) in i-PrOH (3 ml) was then added to the initial mixture in one portion.
The resulting mixture was heated to 50°C for 7 h. After completion of the reaction, it was
filtered and then diluted by EtOAc (5 mL) and saturated NH4Cl solution (5 mL). The mix-
ture was stirred for additional 30 min and two layers were separated. The aqueous layer was
extracted with EtOAc (7 mL × 3). The combined organic layers were dried over MgSO4,
filtered, and concentrated in vacuum. The residue was purified by chromatography (silica
gel, hexane:EtOAc 3:1) to give the pure product (see ESI for characterization data for all
products).
2.1.2.1. Methyl 8-hydroxy-6,10-dioxo-6,10-dihydrobenzo[b]pyrido[1,2-d][1,4]thiazine-
7-carboxylate (4a). Pale yellow powder, m.p.: 267–270°C; yield: 0.27 g (89%). IR (KBr)
(νmax, cm−1): 3490, 1745, 1675, 1620, 1533, 1226. 1H NMR (500.1 MHz, DMSO):
δ
= 3.76 (3 H, s, OCH3), 6.18 (H, s, CH), 7.25–7.48 (3 H, m, 3 CH), 8.17 (H, d,
H
3J = 6.7 Hz, CH), 12.06 (H, br s, OH). 13C NMR(125.7 MHz, DMSO): δ = 53.7 (OCH3),
C
105.2 (CH), 114.1 (C), 117.2 (CH), 120.4 (CH), 125.8 (CH), 127.4 (CH), 128.2 (C), 136.1
(C), 149.7 (C), 161.3 (C), 164.2 (C), 169.5 (C), 181.7 (C). MS: m/z (%) = 303 (M+, 5), 289
(26), 244 (43), 186 (49), 110 (67), 77 (100), 43 (12). Anal. Calcd for C14H9NO5S (303.29):
C, 55.44; H, 2.99; N, 4.62. Found: C, 55.67; H, 3.17; N, 4.57%.
2.1.2.2. Methyl 3-hydroxy-1,5-dioxo-1,5-dihydronaphtho[2,3-b]pyrido[1,2- d][1,4]thia-
zine-4-carboxylate (4b). Pale yellow powder, m.p.: 318–321°C; yield: 0.32 g (92%). IR
(KBr) (νmax, cm−1): 3467, 1740, 1654, 1607, 1524, 1220. 1H NMR (500.1 MHz, DMSO):

JOURNAL OF SULFUR CHEMISTRY
7
δ
= 3.84 (3 H, s, OCH3), 6.12 (1 H, s, CH), 6.86 (1 H, s, CH), 7.19–7.28 (2 H, m, 2
H
CH), 7.51–7.63 (2 H, m, 2 CH), 8.19 (1 H, d, 3J = 6.7 Hz, CH), 11.25 (1 H, br s, OH). 13
C
NMR(125.7 MHz, DMSO): δ = 53.7 (OCH3), 97.8 (CH), 111.3 (C), 122.2 (CH), 123.1
C
(CH), 126.4 (C), 126.8 (CH), 127.1 (C), 127.7 (C), 128.3 (CH), 130.2 (C), 131.0 (C), 139.7
(C), 154.1 (C), 162.8 (C), 165.4 (C), 171.6 (C), 180.9 (C). MS: m/z (%) = 353 (M+, 2),
339 (17), 294 (33), 236 (61), 127 (100), 110 (72). Anal. Calcd for C18H11NO5S (353.35): C,
61.19; H, 3.14; N, 3.96. Found: C, 61.36; H, 3.28; N, 4.03%.
2.1.2.3. Methyl 3-chloro-8-hydroxy-6,10-dioxo-6,10-dihydrobenzo[b]pyrido[1,2-d][1,4]
thiazine-7-carboxylate (4c). Pale yellow powder, m.p.: 289–292°C; yield: 0.29 g (85%). IR
(KBr) (νmax, cm−1): 3467, 1751, 1647, 1607, 1524, 1213. 1H NMR (500.1 MHz, DMSO):
δ
= 3.82 (3 H, s, OCH3), 6.17 (1 H, s, CH), 7.24 (1 H, d, 3J = 7.0 Hz, CH), 7.41 (1 H,
H
s, 1 CH), 8.27 (1 H, d, J = 7.0 Hz, CH), 12.17 (1 H, br s, OH). 13C NMR(125.7 MHz,
3
DMSO): δ = 53.5 (OCH3), 105.4 (CH), 116.7 (C), 123.2 (CH), 123.6 (CH), 125.4 (CH),
C
127.9 (C), 132.8 (C), 140.6 (C), 155.2 (C), 161.4 (C), 165.3 (C), 169.2 (C), 181.3 (C). MS:
m/z (%) = 337 (M+, 2), 321 (14), 278 (24), 220 (35), 111 (100), 110 (78). Anal. Calcd for
C14H8ClNO5S (337.73): C, 49.79; H, 2.39; N, 4.15. Found: C, 49.94; H, 2.46; N, 4.29%.
2.1.2.4. Methyl 2-chloro-8-hydroxy-6,10-dioxo-6,10-dihydrobenzo[b]pyrido[1,2-d][1,4]
thiazine-7-carboxylate (4d). Pale yellow powder, m.p.: 281–284°C; yield: 0.28 g (82%). IR
(KBr) (νmax, cm−1): 3469, 1748, 1662, 1611, 1541, 1215. 1H NMR (500.1 MHz, DMSO):
δ
= 3.79 (3 H, s, OCH3), 6.17 (1 H, s, CH), 7.27–7.38 (2 H, m, 2 CH), 8.07 (1 H, s, CH),
H
12.22 (1 H, br s, OH). 13C NMR(125.7 MHz, DMSO): δ = 53.5 (OCH3), 106.3 (CH),
C
115.6 (C), 119.2 (CH), 122.1 (CH), 130.4 (CH), 131.3 (C), 136.5 (C), 140.2 (C), 155.7 (C),
161.2 (C), 165.4 (C), 170.1 (C), 183.7 (C). MS: m/z (%) = 337 (M+, 2), 321 (28), 278 (37),
220 (40), 111 (100), 110 (78). Anal. Calcd for C14H8ClNO5S (337.73): C, 49.79; H, 2.39; N,
4.15. Found: C, 49.87; H, 2.58; N, 4.21%.
2.1.2.5. Methyl 3-methyl-8-hydroxy-6,10-dioxo-6,10-dihydrobenzo[b]pyrido[1,2-d][1,4]
thiazine-7-carboxylate (4e). Pale yellow powder, m.p.: 273–276°C; yield: 0.28 g (89%). IR
(KBr) (νmax, cm−1): 3476, 1751, 1660, 1606, 1545, 1211. 1H NMR (500.1 MHz, DMSO):
δ
= 2.32 (3 H, s, CH3), 3.72 (3 H, s, OCH3), 6.15 (1 H, s, CH), 7.06 (1 H, d, 3J = 6.8 Hz,
H
CH), 7.12 (1 H, s, CH), 8.11 (1 H, d, J = 6.9 Hz, CH), 12.06 (1 H, br s, OH). 13C
3
NMR(125.7 MHz, DMSO): δ = 20.4 (CH3), 52.9 (OCH3), 103.5 (CH), 116.3 (C), 118.5
C
(CH), 121.2 (CH), 126.7 (CH), 133.2 (C), 137.5 (C), 138.0 (C), 154.4 (C), 161.2 (C), 164.8
(C), 170.1 (C), 183.9 (C). MS: m/z (%) = 317 (M+, 3), 303 (14), 258 (37), 200 (41), 110
(100), 91 (56). Anal. Calcd for C15H11NO5S (317.32): C, 56.78; H, 3.49; N, 4.41. Found: C,
56.94; H, 3.59; N, 4.43%.
2.1.2.6. Methyl 2-methyl-8-hydroxy-6,10-dioxo-6,10-dihydrobenzo[b]pyrido[1,2-d][1,4]
thiazine-7-carboxylate (4f). Pale yellow powder, m.p.: 280–283°C; yield: 0.29 g (90%). IR
(KBr) (νmax, cm−1): 3462, 1741, 1652, 1608, 1547, 1236. 1H NMR (500.1 MHz, DMSO):
δ
= 2.30 (3 H, s, CH3), 3.80 (3 H, s, OCH3), 6.11 (1 H, s, CH), 7.21–7.29 (2 H, m, 2 CH),
H
8.01 (1 H, s, CH), 11.97 (1 H, br s, OH). 13C NMR(125.7 MHz, DMSO): δ = 21.7 (CH3),
C
53.5 (OCH3), 106.1 (CH), 114.7 (C), 120.8 (CH), 123.4 (CH), 127.6 (CH), 133.1 (C), 135.6
(C), 139.6 (C), 154.7 (C), 161.3 (C), 164.9 (C), 171.8 (C), 184.5 (C). MS: m/z (%) = 317

8
A. SAMZADEH-KERMANI
(M+, 8), 303 (24), 258 (46), 200 (72), 110 (100), 91 (42). Anal. Calcd for C15H11NO5S
(317.32): C, 56.78; H, 3.49; N, 4.41. Found: C, 57.05; H, 3.67; N, 4.40%.
2.1.2.7. Methyl 8-hydroxy-2-methoxy-6,10-dioxo-6,10-dihydrobenzo[b]pyrido[1,2-d]
[1,4]thiazine-7-carboxylate (4g). Pale yellow powder, m.p.: 302–305°C; yield: 0.32 g
(96%). IR (KBr) (νmax, cm−1): 3457, 1747, 1656, 1607, 1546, 1211. 1H NMR (500.1 MHz,
DMSO): δ = 3.65 (3 H, s, OCH3), 3.69 (3 H, s, OCH3), 6.04 (1 H, s, CH), 6.79 (1 H, d,
H
3J = 7.0 Hz, CH), 7.14 (1 H, d, 3J = 7.1 Hz, CH), 7.76 (1 H, s, CH), 10.76 (H, br s, OH).
13C NMR(125.7 MHz, DMSO): δ = 54.6 (OCH3), 56.1 (OCH3), 98.6 (CH), 108.9 (CH),
C
112.6 (CH), 116.3 (C), 128.3 (CH), 129.7 (C), 137.6 (C), 154.4 (C), 157.8 (C), 160.2 (C),
167.0 (C), 172.5 (C), 184.8(C). MS: m/z (%) = 333 (M+, 2), 319 (12), 275 (35), 216 (47),
275 (35), 110 (69), 108 (100). Anal. Calcd for C15H11NO6S (333.31): C, 54.05; H, 3.33; N,
4.20. Found: C, 54.28; H, 3.52; N, 4.31%.
2.1.2.8. Methyl 2-bromo-8-hydroxy-6,10-dioxo-6,10-dihydrobenzo[b]pyrido[1,2-d][1,4]
thiazine-7-carboxylate (4h). Pale yellow powder, D.p: 350˚C; yield: 0.31 g (81%). IR
(KBr) (νmax, cm−1): 3380, 1746, 1652, 1612, 1546, 1217. 1H NMR (500.1 MHz, DMSO):
3
δ
= 3.68 (3 H, s, OCH3), 6.02 (1 H, s, CH), 7.29 (1 H, d, J = 6.8 Hz, CH), 7.53 (1
H
H, d, J = 6.9 Hz, CH), 7.93 (1 H, s, CH), 11.87 (H, br s, OH). 13C NMR(125.7 MHz,
3
DMSO): δ = 54.7 (OCH3), 102.7 (CH), 116.7 (C), 120.6 (CH), 124.0 (C), 128.4 (CH),
C
129.7 (CH), 134.2 (C), 138.7 (C), 154.2 (C), 161.1 (C), 165.8 (C), 172.0 (C), 183.5 (C). MS:
m/z (%) = 382 (M+, 5), 367 (14), 323 (37), 265 (52), 155 (52), 110 (100). Anal. Calcd for
C14H8BrNO5S (382.182): C, 44.00; H, 2.11; N, 3.66. Found: C, 44.12; H, 2.27; N, 3.82%.
2.1.2.9. Methyl 3-(tert-butyl)-8-hydroxy-6,10-dioxo-6,10-dihydrobenzo[b]pyrido[1,2-d]
[1,4]thiazine-7-carboxylate (4i). Pale yellow powder, m.p.: 316–319˚C; yield: 0.31 g
(87%). IR (KBr) (νmax, cm−1): 3380, 1751, 1656, 1611, 1547, 1223. 1H NMR (500.1 MHz,
DMSO): δ = 1.32 (9 H, s, 3 CH3), 3.62 (3 H, s, OCH3), 6.21 (1 H, s, CH), 7.26–7.37 (2
H
H, m, 2 CH), 7.96 (1 H, d, 3J = 6.9 Hz, CH), 11.79 (1 H, br s, OH). 13C NMR(125.7 MHz,
DMSO): δ = 27.4 (3 CH3), 45.1 (C), 56.4 (OCH3), 103.8 (CH), 112.6 (C), 119.1 (CH),
C
121.5 (CH), 123.9 (CH), 133.5 (C), 137.2 (C), 145.1 (C), 154.7 (C), 162.5 (C), 166.1 (C),
171.7 (C), 183.3 (C). MS: m/z (%) = 359 (M+, 4), 345 (17), 301 (25), 242 (35), 133 (86),
110 (76), 57 (100). Anal. Calcd for C18H17NO5S (359.40): C, 60.16; H, 4.77; N, 3.90. Found:
C, 60.32; H, 4.93; N, 4.05%.
2.1.2.10. Ethyl8-hydroxy-6,10-dioxo-6,10-dihydrobenzo[b]pyrido[1,2-d][1,4]thiazine-7-
carboxylate (4j). Pale yellow powder, m.p.: 279–282°C; yield: 0.27 g (86%). IR (KBr) (ν
,
max
cm−1): 3368, 1744, 1668, 1601, 1526, 1217. 1H NMR (500.1 MHz, DMSO): δ = 1.29 (3
H
H, t, 3J = 6.4 Hz, CH3), 4.27 (2 H, q, 3J = 6.7 Hz, CH2), 6.14 (1 H, s, CH), 7.11 (1 H, t,
3J = 7.0 Hz, CH), 7.18 (1 H, t, 3J = 7.1 Hz, CH), 7.41 (1 H, d, 3J = 6.7 Hz, CH), 8.17 (1 H,
d, 3J = 6.8 Hz, CH), 12.11 (1 H, s, OH). 13C NMR(125.7 MHz, DMSO): δ = 15.2 (CH3),
C
62.6 (CH2), 104.4 (CH), 112.7 (C), 122.1 (CH), 124.6 (CH), 124.8 (CH), 125.7 (CH), 135.1
(C), 137.5 (C), 152.6 (C), 161.8 (C), 165.4 (C), 173.5 (C), 183.6 (C). MS: m/z (%) = 317
(M+, 1), 289 (15), 245 (27), 186 (34), 110 (100), 77 (78). Anal. Calcd for C15H11NO5S
(317.32): C, 56.78; H, 3.49; N, 4.41. Found: C, 56.95; H, 3.64; N, 4.38%.

JOURNAL OF SULFUR CHEMISTRY
9
2.1.2.11. Tert-butyl 8-hydroxy-6,10-dioxo-6,10-dihydrobenzo[b]pyrido[1,2-d][1,4]thia-
zine-7-carboxylate (4k). Pale yellow powder, m.p.: 313–316°C; yield: 0.32 g (92%). IR
(KBr) (νmax, cm−1): 3379, 1751, 1646, 1611, 1547, 1213. 1H NMR (500.1 MHz, DMSO):
δ
= 1.61 (9 H, s, 3 CH3), 6.16 (1 H, s, CH), 7.11–7.26 (3 H, m, 3 CH), 7.98 (1 H, d,
H
3J = 6.8 Hz, CH), 11.89 (1 H, s, OH). 13C NMR(125.7 MHz, DMSO): δ = 29.8 (3 CH3),
C
80.2 (C), 101.8 (CH), 112.3 (C), 121.1 (CH), 122.5 (CH), 123.6 (CH), 123.9 (CH), 134.1 (C),
137.5 (C), 155.7 (C), 160.9 (C), 166.3 (C), 170.6 (C), 182.2 (C). MS: m/z (%) = 345 (M+,
2), 289 (19), 245 (33), 186 (51), 110 (69), 77 (86), 57 (100). Anal. Calcd for C17H15NO5S
(345.37): C, 59.12; H, 4.38; N, 4.06. Found: C, 59.21; H, 4.56; N, 4.12%.
2.1.2.12. Methyl-2-(2-oxo-2H-benzo[b][1,4]thiazin-3(4H)-ylidene)acetate (7). Yellow
powder, m.p.: 143–146.5°C; yield: 0.22 g (93%). IR (KBr) (νmax, cm−1): 3371, 1740, 1628,
1531, 1134. 1H NMR (500.1 MHz, DMSO): δ = 3.67 (3 H, s, OCH3), 6.87 (H, s, CH), 6.31
H
(H, d, 3J = 6.7 Hz, CH), 7.06–7.13 (2 H, m, 2 CH), 7.56 (H, d, 3J = 7.1 Hz, CH), 12.24 (H,
br s, NH). 13C NMR(125.7 MHz, DMSO): δ = 54.1 (OCH3), 111.8 (CH), 115.6 (CH),
C
119.9 (CH), 123.5 (CH), 134.1 (CH), 137.0 (C), 148.1 (C), 163.1 (C), 167.4 (C), 184.1 (C).
Anal. Calcd for C11H9NO3S (235.26): C, 56.16; H, 3.86; N, 5.95. Found: C, 57.00; H, 4.41;
N, 5.78%.
Disclosure statement
No potential conflict of interest was reported by the author.
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