Synthesis of coumarin substituted triazolothiadiazine derivatives via ring transformation reaction

Article abstract of DOI:10.1002/jhet.958

A novel ring transformation reaction for the synthesis of 3-(3-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazin-6-yl)-2H-chromen-2-ones has been described. Reaction of 3-(2-bromoacetyl)coumarins (1) with 5-aryl-1,3,4-oxadiazole-2-thiol (2) gave ketones (4a-h). The in situ formed ketones (4a-h) were reacted with hydrazine hydrate to give 3-(3-aryl-7H-[1,2,4] triazolo[3,4-b][1,3,4]thiadiazin-6-yl)-2H-chromen-2-ones (3a-h) and not 5 or 6. The compounds (3a-h) can also be prepared by the reaction of 3-(2-bromoacetyl)coumarins (1) with 5-aryl-1,3,4-oxadiazole-2-thiol (2) in anhydrous ethanol to give corresponding 3-(2-(5-aryl-1,3,4-oxadiazol-2-ylthio) acetyl)-2H-chromen-2-ones (4a-h). These on reaction with hydrazine hydrate in acetic acid gave corresponding 3-(3-aryl-7H-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazin-6-yl)-2H-chromen-2-ones (3a-h).

Full text of DOI:10.1002/jhet.958

January 2013
Synthesis of Coumarin Substituted Triazolothiadiazine
159
Derivatives via Ring Transformation Reaction
*
Venkata Sreenivasa Rao Chunduru and Vedula Rajeswar Rao
Department of Chemistry, National Institute of Technology, Warangal,
Andhra Pradesh 506 004, India
*
E-mail: vrajesw@yahoo.com
Received November 30, 2010
DOI 10.1002/jhet.958
View this article online at wileyonlinelibrary.com.
A novel ring transformation reaction for the synthesis of 3‐(3‐aryl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐
6‐yl)‐2H‐chromen‐2‐ones has been described. Reaction of 3‐(2‐bromoacetyl)coumarins (1) with 5‐aryl‐1,3,
4‐oxadiazole‐2‐thiol (2) gave ketones (4a–h). The in situ formed ketones (4a–h) were reacted with hydrazine
hydrate to give 3‐(3‐aryl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐chromen‐2‐ones (3a–h) and not
5 or 6. The compounds (3a–h) can also be prepared by the reaction of 3‐(2‐bromoacetyl)coumarins (1) with
5‐aryl‐1,3,4‐oxadiazole‐2‐thiol (2) in anhydrous ethanol to give corresponding 3‐(2‐(5‐aryl‐1,3,4‐oxadiazol‐2‐
ylthio)acetyl)‐2H‐chromen‐2‐ones (4a–h). These on reaction with hydrazine hydrate in acetic acid gave
corresponding 3‐(3‐aryl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐chromen‐2‐ones (3a–h).
J. Heterocyclic Chem., 50, 159 (2013).
INTRODUCTION
as anti‐invasive compounds due to their inhibitory activity
against serine proteases and matrix metalloproteases
(MMPs) [16].
In the last few decades, the chemistry of 1,2,4‐triazoles and
their fused heterocyclic system have received considerable
attention due to their synthetic and effective biological
importance. The biological activities of various 1,2,4‐triazole
derivatives have been extensively studied. Many of these
derivatives exhibit antiviral, potential analgesic, anti‐
inflammatory, CNS stimulants, sedatives, antianxiety, and
antimicrobial activities [1–4]. These derivatives also act as
antimycotic agents [5], [6]. The triazole fused with six‐
membered ring system like thiadiazine is also found to
possess various applications in the field of medicine. The
literature survey reveals that there are few examples of
triazoles fused with thiadiazines. These fused 1,2,4‐triazolo
[3,4‐b][1,3,4]thiadiazines exhibit a broad spectrum of
antimicrobial activity [7–11] due to N C S linkage.
Benzopyran‐2‐one derivatives also called coumarins, and
related compounds exhibit various biological activities,
including anticoagulant and antithrombotic properties
[12]. These derivatives have also been shown to be novel
lipid lowering agents that possess moderate triglyceride
lowering activity [13]. Many coumarin derivatives have
the unique ability to scavenge reactive oxygen species
such as hydroxyl free radicals, super oxide radicals, or
hypochlorous acid to prevent free radical injury [14]. Recently,
certain coumarin derivatives have been shown to function as
human immunodeficiency virus (HIV) integrase inhibitors
and have been evaluated in the treatment of HIV infection
[15]. Some of the coumarin derivatives have been evaluated
On the basis of these investigations and in continuation
of our research work on the synthesis of novel heterocyclic
compounds [17–21], it was thought to be interesting to
synthesize compounds containing the fused ring system
[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazine substituted with
2H‐benzopyran‐2‐one. The newly synthesized compounds
might result in enhanced biological activities, lead to use in
drug discovery.
RESULTS AND DISCUSSION
Reaction of equimolar mixture of 3‐(2‐bromoacetyl)cou-
marin 1 and 5‐aryl‐1,3,4‐oxadiazole‐2‐thiol 2 in AcOH/
AcONa at 60°C for 1 h, followed by the addition of hydra-
zine hydrate and heating the reaction mixture for another 2
h led to a fused ring system 3‐(3‐aryl‐7H‐[1,2,4]triazolo
[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐chromen‐2‐ones 3a–h in
good yields (Scheme 1). The reaction of 1 with 2 gave
compound 4. The in situ generated compound 4 on reac-
tion with hydrazine hydrate may give two types of cyclized
products like 5 and 6 or both. The cyclocondensation prod-
uct 5 having pyrazole fused to benzopyran‐2‐one is be-
lieved to be obtained via Michael reaction [22]. On the
other hand, another cyclo product 6 may be obtained
through intramoleculer amidation reaction. But in our case
only one product 3 (by TLC) is obtained in a selective ring
© 2013 HeteroCorporation

160
V. S. R. Chunduru and V. Rajaswar Rao
Vol 50
Scheme 1. One‐pot synthesis of 3‐(3‐aryl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐chromen‐2‐ones (3a–h).
transformation process (Scheme 2). The structures of
compounds 3a–h were established on the basis of their
spectral and analytical data.
ring at δ 24.4 and δ 164.6, respectively. The IR spectrum
of 3a and 3e showed strong peaks at 1724 cm−1 and
1715 cm−1, respectively, which were attributed to the lactone
of coumarin. All the above spectral data supports the forma-
tion of the title products.
1
The H‐NMR spectra of 3a showed three singlets at δ
2.37, δ 4.32, and δ 8.60 ppm because of the methyl,
CH2 protons of thiadiazine and C‐4 proton of coumarin,
The compounds 3a–h can also be synthesized by alternative
method involving condensation of 3‐(2‐bromoacetyl)
coumarins with 5‐aryl‐1,3,4‐oxadiazole‐2‐thiol in anhydrous
ethanol to yield the corresponding 3‐(2‐(5‐aryl‐1,3,4‐
oxadiazol‐2‐ylthio)acetyl)‐2H‐chromen‐2‐ones 4a–h in good
yields (Scheme 3). These on reaction with hydrazine hydrate
1
respectively. Similarly, the H‐NMR spectra of 3e shows
singlets at δ 4.12 and δ 8.34 because of the CH2 protons
of thiadiazine and C‐4 proton of coumarin, respectively.
The 13C‐NMR spectra of compound 3a also shows charac-
teristic peaks for CH2 of thiadiazine and C O of coumarin
Scheme 2. Plausible mechanism for the formation of products (3a–h).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2013
Synthesis of Coumarin Substituted Triazolothiadiazine Derivatives via
161
Ring Transformation Reaction
Scheme 3. 3‐(3‐Aryl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐chromen‐2‐one (4a–h) by two‐step method.
Method-II
hydrazine hydrate (1 mmol) was added and heated at 80–85°C
for about 2 h. After completion of the reaction, the reaction
mixture was cooled to room temperature and poured in water.
The solid separated was filtered, washed with water, and
recrystallized from ethanol.
resulted in the formation of 3a–h. The products obtained by
both the methods were found to be identical by mixed
melting point measurements, Co‐TLC and spectral data.
The yields obtained by both the methods were shown in
Table 1. The yields obtained by method‐I were found to
be good when compared to the method‐II.
The ring closer was verified by the disappearance of the
C O absorptions in the IR spectra of 3a–h and by the up‐field
shift of the CH2 protons in the 1H‐NMR spectra of 3a–h.
3‐(3‐p‐Tolyl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐
2H‐chromen‐2‐one (3a). Color: yellow; mp 251–253°C (252°C)
[24]; IR (potassium bromide): 1608 (C N), 1724 (O C O), 3052
( C H) cm−1 1H‐NMR (deuteriochloroform): δ 2.37 (s, 3H,
;
CH3), 4.32 (s, 2H, S CH2), 7.35–7.46 (m, 4H, ArH), 7.74 (d,
2H, J = 8 Hz, ArH), 7.90 (d, 2H, J = 7.6 Hz, ArH), 8.60 (s, 1H,
C‐4 of coumarin); 13C‐NMR (deuteriochloroform): δ 21.4, 24.4,
116.8, 118.3, 122.8, 125.3, 126.5, 128.1, 129.5, 134.0, 140.8,
142.9, 145.0, 152.0, 152.8, 154.5, 159.3, 164.6; EI‐MS 375
[M + H]+. Anal. Calcd for C20H14N4O2S: C, 64.16; H, 3.77;
N, 14.96; S, 8.56; Found: C, 64.10; H, 3.73; N, 14.90; S, 8.51.
8‐Methoxy‐3‐(3‐p‐tolyl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐
6‐yl)‐2H‐chromen‐2‐one (3b). Color: yellow; mp 184–186°C; IR
(potassium bromide): 1610 (C N), 1720 (O C O), 3047 ( C H)
CONCLUSION
In conclusion, we have developed a novel ring trans-
formation reaction for synthesis of 3‐(3‐aryl‐7H‐[1,2,4]
triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐chromen‐2‐ones
via one‐pot reaction and also unambiguously. This protocol
can provide a novel and effective methodology for the
preparation of this type of compound using readily available
starting materials. The biological activity of these compounds
is under investigation.
1
cm−1; H‐NMR (deuteriochloroform): δ 2.40 (s, 3H, CH3), 4.00
(s, 3H, OMe), 4.10 (s, 2H, S CH2), 7.18–7.21 (m, 3H, ArH), 7.29
(d, 2H, J = 8 Hz, ArH), 7.92 (d, 2H, J = 8.0 Hz, ArH), 8.30 (s,
1H, C‐4 of coumarin); 13C‐NMR (deuteriochloroform): 21.4,
24.3, 56.3, 115.6, 118.9, 120.6, 122.4, 122.8, 124.0, 125.2, 129.3,
140.7, 142.9, 144.2, 145.2, 147.1, 152.8, 158.9, 164.7; EI‐MS
405 [M + H]+. Anal. Calcd for: C21H16N4O3S: C, 62.36; H, 3.99;
N, 13.85; S, 7.93; Found: C, 62.30; H, 3.94; N, 13.89; S, 7.88.
EXPERIMENTAL
General. All the reagents, solvents and 5‐aryl‐1,3,4‐oxadiazole‐
2‐thiol were purchased from commercial sources and were used
without any further purification unless otherwise stated. 3‐(2‐
Bromoacetyl)coumarins [23] were prepared according to the
literature procedure. Melting points were determined in open
capillaries with a “Cintex” melting point apparatus Mumbai,
India and were uncorrected. CHNS analysis was done by Carlo
Erba EA 1108 automatic elemental analyzer. The purity of the
compounds was checked by TLC plates (E. Merck Mumbai,
India). IR spectra (KBr) were recorded on a Bruker WM‐4(X)
Table 1
Comparison of yields by both the methods for the synthesis of
3‐(3‐aryl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐
2H‐chromen‐2‐one (3a–h).
Yield (%) in
Yield (%) in
S. no.
Entry
method‐Ia
method‐IIb
1
spectrometer (577 Model). H‐NMR spectra were recorded on
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
85
83
80
85
86
83
80
81
76
74
76
72
80
79
75
77
the Bruker WM‐400 spectrometer in δ ppm using TMS as
standard. Mass spectra (EI‐MS) were determined on Perkin
Elmer (SCIEX API‐ 2000, ESI) at 12.5 eV.
General procedure for the synthesis of 3‐(3‐aryl‐7H‐[1,2,4]
triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐chromen‐2‐one (3a–h).
To a solution containing 3‐(2‐bromoacetyl)coumarin (1 mmol),
2‐mercapto‐5‐aryl‐1,3,4‐oxadiazole (1 mmol) and sodium acetate
(1 mmol) in acetic acid (5 mL) were heated at 60–65°C for about
1 h. The reaction mixture was cooled to room temperature,
3g
3h
aIsolated yields of 3a–h via one‐pot method.
bIsolated yields 3a–h via two‐step method.
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6,8‐Dibromo‐3‐(3‐p‐tolyl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]
temperature, the solid separated was filtered and recrystallized
from ethanol.
thiadiazin‐6‐yl)‐2H‐chromen‐2‐one (3c). Color: yellow; mp
200–202°C; IR (potassium bromide): 1618 (C N), 1730 (O C O),
3064 ( C H) cm−1; 1H‐NMR (dimethyl sulfoxide d6): δ 2.32
(s, 3H, CH3), 4.15 (s, 2H, S CH2), 7.48–7.62 (m, 4H, ArH), 8.14
(s, 1H, ArH), 8.35 (s, 1H, ArH), 8.68 (s, 1H, C‐4 of coumarin).
13C‐NMR (dimethyl sulfoxide d6): 19.0, 24.8, 116.2, 118.5 119.6,
126.6, 128.2, 128.6, 129.2, 129.6, 133.3, 133.8, 138.8, 145.4,
152.5, 153.6, 158.8, 167.6. Anal. Calcd for: C20H12Br2N4O2S: C,
45.14; H, 2.27; N, 10.53; S, 6.02; Found: C, 45.18; H, 2.24; N,
10.49; S, 5.98.
3‐(2‐(5‐p‐Tolyl‐1,3,4‐oxadiazol‐2‐ylthio)acetyl)‐2H‐chromen‐
2‐one (4a). Yield 85%, mp 200–202°C, Color: yellow; IR
(potassium bromide): 1606 (C N), 1676 ( C O), 1732 (O C O),
3042 ( C H) cm−1 1H‐NMR (deuteriochloroform): δ 2.41
;
(s, 3H, CH3), 4.87 (s, 2H, S CH2), 7.28 (d, 2H, J = 8 Hz, ArH),
7.38–7.43 (m, 2H, ArH), 7.68 (d, 2H, J = 7.6Hz, ArH), 7.87
(d, 2H, J = 8 Hz, ArH), 8.63 (s, 1H, C‐4 of coumarin). EI‐MS
379 [M + H]+. Anal. Calcd for C20H14N2O4S: C, 63.48; H, 3.73;
N, 7.40; S, 8.47; Found: C, 63.41; H, 3.71; N, 7.44; S, 8.41.
3‐(2‐(5‐p‐Tolyl‐1,3,4‐oxadiazol‐2‐ylthio)acetyl)‐8‐methoxy‐2H‐
chromen‐2‐one (4b). Yield 88%, mp 214–216°C, Color: yellow; IR
(potassium bromide): 1599 (C N), 1681 ( C O), 1720 (O C O), 3084
2‐(3‐p‐Tolyl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐
3H‐benzo[f]chromen‐3‐one (3d). Color: yellow; mp 186–188°C;
IR (potassium bromide): 1604 (C N), 1720 (O C O), 3057 ( C H)
1
1
cm−1; H‐NMR (deuteriochloroform): δ 2.40 (s, 3H, CH3), 4.18
( C H) cm−1; H‐NMR (deuteriochloroform): δ 2.38 (s, 3H, CH3),
(s, 2H, S CH2), 7.29 (d, 2H, J = 8 Hz, ArH), 7.54 (d, 1H, J = 8
Hz, ArH), 7.64 (d, 1H, J = 8 Hz, ArH), 7.73–7.99 (m, 4H,
ArH), 8.12–8.17 (m, 1H, ArH), 8.28 (d, 1H, J = 8.4 Hz, ArH),
9.12 (s, 1H, C‐4 of coumarin). EI‐MS 425 [M + H]+. Anal.
Calcd for C24H16N4O2S: C, 67.91; H, 3.80; N, 13.20; S, 7.55;
Found: C, 67.95; H, 3.75; N, 13.17; S, 7.51.
3‐(3‐Phenyl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐
chromen‐2‐one (3e). Color: yellow; mp 248–250°C (ref. [24], 250°
C); IR (potassium bromide): 1602 (C N), 1715 (O C O), 3054
( C H) cm−1; 1H‐NMR (deuteriochloroform): δ 4.12 (s, 2H, S CH2),
7.39–7.50 (m, 5H, ArH), 7.64–7.69 (m, 2H, ArH), 8.05 (m, 2H,
ArH), 8.34 (s, 1H, C‐4 of coumarin). EI‐MS 361 [M + H]+. Anal.
Calcd for C19H12N4O2S: C, 63.32; H, 3.36; N, 15.55; S, 8.90;
Found: C, 63.25; H, 3.31; N, 15.51; S, 8.84.
4.10 (s, 3H, OMe), 4.84 (s, 2H, S CH2), 7.25–7.48 (m, 5H, ArH),
7.88–7.96 (m, 2H, ArH), 8.32 (s, 1H, C‐4 of coumarin). EI‐MS
409 [M + H]+. Anal. Calcd for C21H16N2O5S: C, 61.76; H, 3.95;
N, 6.86; S, 7.85; Found: C, 61.74; H, 3.90; N, 6.81; S, 7.82.
3‐(2‐(5‐p‐Tolyl‐1,3,4‐oxadiazol‐2‐ylthio)acetyl)‐6,8‐dibromo‐
2H‐chromen‐2‐one (4c). Yield 83%, mp 192–194°C; Color:
yellow; IR (potassium bromide): 1600 (C N), 1678 ( C O), 1725
1
(O C O), 3063 ( C H) cm−1; H‐NMR (dimethyl sulfoxide d6): δ
2.43 (s, 3H, CH3), 4.86 (s, 2H, S CH2), 7.50 (d, 2H, J = 7.2 Hz,
ArH), 7.73–7.81 (m, 2H, ArH), 7.99 (m, 2H, ArH), 8.36 (s, 1H,
C‐4 of coumarin). Anal. Calcd for C20H12Br2N2O4S: C, 44.80; H,
2.26; N, 5.22; S, 5.98; Found: C, 44.75; H, 2.30; N, 5.20; S, 5.91.
2‐(2‐(5‐p‐Tolyl‐1,3,4‐oxadiazol‐2‐ylthio)acetyl)‐3H‐benzo[f]
chromen‐3‐one (4d). Yield 90%, mp 176–178°C; Color: yellow;
IR (potassium bromide): 1599 (C N), 1683 ( C O), 1716 (O C O),
3053 ( C H) cm−1; 1H‐NMR (deuteriochloroform): δ 2.38 (s, 3H,
CH3), 5.12 (s, 2H, S CH2), 7.38 (d, 2H, J = 8 Hz, ArH), 7.70
(d, 2H, J = 8.4 Hz, ArH), 7.85 (d, 3H, J = 8 Hz, ArH), 8.13
(d, 1H, J = 8 Hz, ArH), 8.42 (d, 1H, J = 9.2 Hz, ArH), 8.71
(d, 1H, J = 8.4 Hz, ArH), 9.49 (s, 1H, C‐4 of coumarin). EI‐MS
429 [M +H]+. Anal. Calcd for C24H16N2O4S: C, 67.28; H, 3.76;
N, 6.54; S, 7.48; Found: C, 67.23; H, 3.71; N, 6.59; S, 7.42.
3‐(2‐(5‐Phenyl‐1,3,4‐oxadiazol‐2‐ylthio)acetyl)‐2H‐chromen‐
2‐one (4e). Yield 85%, mp 210–212°C; Color: yellow; IR
(potassium bromide): 1610 (C N), 1680 ( C O), 1701
8‐Methoxy‐3‐(3‐phenyl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐
6‐yl)‐2H‐chromen‐2‐one (3f). Color: yellow; mp 210–212°C; IR
(potassium bromide): 1606 (C N), 1730 (O C O), 3039 ( C H)
1
cm−1; H‐NMR (deuteriochloroform): δ 3.86 (s, 3H, OMe), 4.20
(s, 2H, S CH2), 7.26–7.48 (m, 7H, ArH), 7.91 (s, 1H, ArH), 8.32
(s, 1H, C‐4 of coumarin). EI‐MS 391 [M + H]+. Anal. Calcd for
C20H14N4O3S: C, 61.53; H, 3.61; N, 14.35; S, 8.21; Found: C,
61.50; H, 3.58; N, 14.30; S, 8.15.
6,8‐Dibromo‐3‐(3‐phenyl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]
thiadiazin‐6‐yl)‐2H‐chromen‐2‐one (3g). Color: yellow;
mp 222–224°C; IR (potassium bromide): 1610 (C N), 1730
(O C O), 3053 ( C H) cm−1
;
1H‐NMR (dimethyl sulfoxide
(O C O), 3032 ( C H) cm−1 1H‐NMR (deuteriochloroform):
;
d6): δ 3.98 (s, 2H, S CH2), 7.60–7.78 (m, 5H, ArH), 8.15
(s, 1H, ArH), 8.34 (s, 1H, ArH), 8.76 (s, 1H, C‐4 of coumarin).
13C‐NMR (dimethyl sulfoxide d6): 23.8, 117.1, 118.4 119.6,
124.6, 128.2, 128.7, 129.1, 129.7, 132.9, 133.4, 138.6, 145.2,
149.5, 153.2, 159.6, 164.6. Anal. Calcd for C19H10Br2N4O2S: C,
44.04; H, 1.95; N, 10.81; S, 6.19; Found: C, 44.12; H, 1.90; N,
10.85; S, 6.10.
δ 4.70 (s, 2H, S CH2), 7.30–7.54 (m, 5H, ArH), 7.62–7.75
(m, 3H, ArH), 7.98 (d, 1H, J = 8 Hz, ArH), 8.58 (s, 1H, C‐4 of
coumarin). EI‐MS 365 [M + H]+. Anal. Calcd for C19H12N2O4S:
C, 62.63; H, 3.32; N, 7.69; S, 8.80; Found: C, 62.67; H, 3.30; N,
7.73; S, 8.74.
3‐(2‐(5‐Phenyl‐1,3,4‐oxadiazol‐2‐ylthio)acetyl)‐8‐
methoxy‐2H‐chromen‐2‐one (4f). Yield 85%, mp 188–190°C;
Color: yellow; IR (potassium bromide): 1602 (C N), 1681
2‐(3‐Phenyl‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐
3H‐benzo[f]chromen‐3‐one (3h). Color: yellow; mp 194–196°C;
IR (potassium bromide): 1607 (C N), 1706 (O C O), 3042 ( C H)
( C O), 1728 (O C O), 3028 ( C H) cm−1
;
1H‐NMR
(deuteriochloroform): δ 4.00 (s, 3H, OMe), 4.89 (s, 2H,
S CH2), 7.22–7.26 (m, 2H, ArH), 7.29 (d, 1H, J = 8 Hz, ArH),
7.50 (t, 3H, J = 8.4 Hz, ArH), 7.97–8.00 (m, 2H, ArH), 8.60
(s, 1H, C‐4 of coumarin). EI‐MS 395 [M + H]+. Anal. Calcd
for C20H14N2O5S: C, 60.91; H, 3.58; N, 7.10; S, 8.13; Found:
C, 60.88; H, 3.54; N, 7.14; S, 8.10.
cm−1 1H‐NMR (deuteriochloroform): δ 4.08 (s, 2H, S CH2),
;
7.62–7.92 (m, 7H, ArH), 8.12 (d, 1H, J = 8.4, ArH), 8.24
(d, 1H, J = 8.4, ArH), 8.42–8.50 (m, 1H, ArH), 8.24 (d, 1H,
J = 8.4, ArH), 9.14 (s, 1H, C‐4 of coumarin). EI‐MS 411 [M + H]+.
Anal. Calcd for C23H14N4O2S: C, 67.30; H, 3.44; N, 13.65; S, 7.81;
Found: C, 67.35; H, 3.41; N, 13.61; S, 7.75.
General procedure for the synthesis of 3‐(2‐(5‐aryl‐1,3,4‐
oxadiazol‐2‐ylthio)acetyl)‐2H‐chromen‐2‐ones (4a–h). 3‐(2‐
Bromoacetyl)coumarin (1 mmol) and 2‐mercapto‐5‐aryl‐1,3,
4‐oxadiazole (1 mmol) were taken in 5 mL anhydrous ethanol and
refluxed for about 2 h. Then reaction mixture was cooled to room
3‐(2‐(5‐Phenyl‐1,3,4‐oxadiazol‐2‐ylthio)acetyl)‐6,8‐dibromo‐
2H‐chromen‐2‐one (4g). Yield 83%, mp 200–202°C; Color:
yellow; IR (potassium bromide): 1600 (C N), 1678 ( C O), 1724
1
(O C O), 3063 ( C H) cm−1; H‐NMR (dimethyl sulfoxide d6): δ
5.02 (s, 2H, S CH2), 7.60–7.78 (m, 5H, ArH), 8.12 (s, 1H,
ArH), 8.34 (s, 1H, ArH), 8.68 (s, 1H, C‐4 of coumarin). Anal.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

January 2013
Synthesis of Coumarin Substituted Triazolothiadiazine Derivatives via
163
Ring Transformation Reaction
[3] Tozkoparan, B.; Aktay, G.; Ye Ilada, E. Il Farmaco 2002, 57, 145.
[4] Mathew, V.; Keshavayya, J.; Vaidya, V. P. Eur J Med Chem
2006, 41, 1048.
[5] The Merck Index, Merck Co. Inc., 12th ed., USA, 1996.
[6] Haber, J. Cas Lek Cesk 2001, 140, 596.
[7] Holla, B. S.; Kalluraya, B.; Sridhar, K. R.; Drake, E.; Thomas,
L. M.; Bhandary, K. K.; Levine, M. J. Eur J Med Chem 1994, 29, 301.
[8] Habib, N. S.; Soliman, R.; Ashour, F. A.; el‐Taiebi, M.
Pharmazie 1997, 52, 844.
[9] Holla, B. S.; Akberali, P. M.; Shivananda, M. K. Farmaco
2001, 56, 919.
[10] Khanum, S. A.; Shashikanth, S.; Umesha, S.; Kavitha, R. Eur J
Med Chem 2005, 40, 1156.
[11] Holla, B. S; Sooryanarayana Rao, B.; Sarojini, B. K.; Akberali,
P. M.; Suchetha Kumari, N. Eur J Med Chem 2006, 41, 657.
[12] Hoult, J. R. R.; Paya, M. Gen Pharmacol 1996, 27, 713.
[13] Madhavan, G. R.; Balraju, V.; Mallesham, B.; Chakrabarti, R.;
Lohray, V. B. Bioorg Med Chem Lett 2003, 13, 2547.
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1992, 44, 205.
Calcd for C19H10Br2N2O4S: C, 43.70; H, 1.93; N, 5.36; S, 6.14;
Found: C, 43.75; H, 10.96; N, 5.36; S, 6.10.
2‐(2‐(5‐Phenyl‐1,3,4‐oxadiazol‐2‐ylthio)acetyl)‐3H‐benzo[f]
chromen‐3‐one (4h). Yield 89%, mp 180–182°C; Color: yellow;
IR (potassium bromide): 1599 (C N), 1681 ( C O), 1735 (O C O),
3063 ( C H) cm−1; 1H‐NMR (deuteriochloroform): δ 4.96 (s, 2H,
S CH2), 7.22–7.28 (m, 2H, ArH), 7.47–7.53 (m, 3H, ArH), 7.64
(t, 1H, J = 7.2 Hz, ArH), 7.77 (t, 1H, J = 8.4 Hz, ArH), 7.94–8.01
(m, 2H, ArH), 8.17 (d, 1H, J = 8.8 Hz, ArH), 8.37 (d, 1H, J = 8.4
Hz, ArH), 9.44 (s, 1H, C‐4 of coumarin); EI‐MS 415 [M + H]+.
Anal. Calcd for C23H14N2O4S: C, 66.66; H, 3.40; N, 6.76; S,
7.74; Found: C, 66.61; H, 3.36; N, 6.72, S, 7.66.
General procedure for the synthesis of 3‐(3‐aryl‐7H‐[1,2,4]
triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl)‐2H‐chromen‐2‐one (3a–h)
from compounds 4a–h. To a solution containing compound
4a–h (1 mmol) and hydrazine hydrate (1 mmol) in acetic acid
(5 mL) was heated at 80–85°C for about 2 h. The reaction
mixture was cooled and poured in water. The separated solid
was filtered, washed with water, and recrystallized from ethanol.
[15] Yu, D.; Suzuki, M.; Xie, L.; Morris‐Natschke, S. L.; Lee, K. ‐H.
Med Res Rev 2003, 23, 322.
[16] Kempen, I.; Papapostolou, D.; Thierry, N.; Pochet, L.;
Counerotte, S.; Masereel, B.; Foidart, J. ‐M.; Reboud‐Ravaux, M.;
Noel, A.; Pirotte, B. Br J Cancer 2003, 88, 1111.
[17] Chunduru, V. S. R.; Rajeswar Rao, V. J Chem Res 2010, 4, 50.
[18] Srimanth, K.; Rajeswar Rao, V. J Chem Res 2002, 9, 420.
[19] Rajeswar Rao, V.; Vijaya Kumar, P. Synth Commun 2006, 36,
2157.
Acknowledgments. The authors are thankful to the Director,
NIT, Warangal for providing facilities. One of the authors
(CHVSR) is thankful to the Director for awarding Institute
Fellowship.
[20] Reddy, K. M.; Rajeswar Rao, V. Phosphphorus Sulphur
Silicon Relat Elem 2009, 184, 743.
[21] Srinivas, V.; Rajeswar Rao, V. Indian J Chem 2010, 47B, 115.
[22] El‐Saghier, A. M. M.; Naili, M. B.; Rammash, B. Kh.; Saleh,
N. A.; Kreddanc, K. M. Arkivoc 2007, xvi, 83.
[23] Rajeswar Rao, V.; Padmanabha Rao, T. V. Indian J Chem
1986, 25B, 413.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet