A facile synthesis of novel dihydroindeno[1,2-e][1,2,4]triazolo[3,4-b][1,3, 4]thiadiazines using HTIB

Article abstract of DOI:10.1002/jhet.815

The synthesis of a series of 21 novel 3-alkyl/aryl-7/9-methyl-10,10a- dihydroindeno[1,2-e][1,2,4]triazolo[3,4-b][1,3,4]thiadiazines (4) has been achieved by the cyclocondensation between 4/6-methyl-2-tosyloxy-1-indanones (2) and 3-alkyl/aryl-4-amino-5-mercapto-1,2,4-s-triazoles (3). 4/6-Methyl-2- tosyloxy-1-indanones (2) were readily accessible through hypervalent iodine oxidation of 4/6-methyl-1-indanones using [(hydroxy)tosyloxyiodo]benzene (HTIB, Koser's reagent) in acetonitrile.

Full text of DOI:10.1002/jhet.815

566
A Facile Synthesis of Novel Dihydroindeno[1,2-e][1,2,4]triazolo-
[3,4-b][1,3,4]thiadiazines Using HTIB
Vol 49
a
b
b
c
*
Om Prakash, Deepak Kumar Aneja, Deepak Wadhwa, Ravi Kumar,
and Sanjiv Arorab
aInstitute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra 136119Haryana, India
bDepartment of Chemistry, Kurukshetra University, Kurukshetra 136119Haryana, India
cDepartment of Chemistry, Dyal Singh College, Karnal, Haryana, India
*
E-mail: dromprakash50@rediffmail.com
Received October 1, 2010
DOI 10.1002/jhet.815
View this article online at wileyonlinelibrary.com.
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The synthesis of a series of 21 novel 3-alkyl/aryl-7/9-methyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo
[3,4-b][1,3,4]thiadiazines (4) has been achieved by the cyclocondensation between 4/6-methyl-2-tosyloxy-
1-indanones (2) and 3-alkyl/aryl-4-amino-5-mercapto-1,2,4-s-triazoles (3). 4/6-Methyl-2-tosyloxy-1-inda-
nones (2) were readily accessible through hypervalent iodine oxidation of 4/6-methyl-1-indanones using
[(hydroxy)tosyloxyiodo]benzene (HTIB, Koser’s reagent) in acetonitrile.
J. Heterocyclic Chem., 49, 566 (2012).
INTRODUCTION
preferred. Our previous work [13,14] in the area of I(III)
reagents [15] has established that a-tosyloxy ketones, which
were readily accessible through the oxidation of a-ketones
with HTIB, can offer a superior alternate to a-haloketones.
Synthesis of nitrogen containing heterocyclic systems
has been attracting increasing interest over the past decade
because of their utility in various applications. Compounds
bearing the 1,2,4-triazole ring are well known as powerful
antihypertensive [1], antimicrobial [2], anticonvulsant [3],
antidepressant [4], analgesic [5], and antitumorial [6]
agents. Moreover, 1,2,4-triazoles and 1,2,4-triazolo[3,4-b]
[1,3,4]thiadiazines (A) derived from 4-amino-3-mercapto-
1,2,4-triazoles are associated with diverse pharmacological
activities [7–11].
In view of the above facts, it was considered worthwhile
to synthesize novel polycyclic fused thiadiazine com-
pounds containing 1,2,4-triazoles of the type 4, which were
modified from 6-phenyl-7H-[1,2,4]triazolo[3,4-b][1,3,4]
thiadiazines (A) as shown in Figure 1 [12].
The retrosynthetic strategy outlined in the Figure 2
provided us the basis of this work. It was anticipated that
the reaction between a-functionalized indan-1-ones (2)
and 3-alkyl/aryl-4-amino-5-mercapto-1,2,4-s-triazoles (3)
might lead to cyclocondensation reaction thereby giving
target compounds 3-alkyl/aryl-7/9-methyl-10,10a-dihy-
droindeno[1,2-e][1,2,4]triazolo[3,4-b][1,3,4]thiadiazines (4).
The a-substitutent in the case of 2 could be halogen, tosyloxy,
etc. However, due to the hazardous associated with the haloge-
nation of ketones, instability and toxicity of a-haloketones,
alternate approach avoiding these a-haloketones is always
RESULTS AND DISCUSSION
Synthetic route for 3-alkyl/aryl-7/9-methyl-10,10a-
dihydroindeno[1,2-e][1,2,4]triazolo[3,4-b][1,3,4]thiadiazines
(4a–u) is outlined in Scheme 1. Initially, cyclocondensation
was carried out starting from 2-tosyloxy-1-indanone (2a)
and 4-amino-5-mercapto-1,2,4-s-triazoles (3a) in ethanol to
afford the desired product 4a in 90% yield (Scheme 1). Then
we carried out the reaction of different 4/6-methyl-2-tosyloxy-
1-indanones (2b–c) with 3-alkyl/aryl-4-amino-5-mercapto-
1,2,4-s-triazoles (3a–g) under similar conditions. It was found
that the method in all the cases afforded the desired products
4b–u in good to excellent yield.
The a-tosyloxyketones 2a–c were prepared by the oxida-
tion of 1-indanones (1a–c) with HTIB in dichloromethane.
3-Alkyl/aryl-4-amino-5-mercapto-1,2,4-s-triazoles (3a–g)
needed for the present study, were prepared by reported
methods [16].
The structures of all the new a-tosyloxyketones 2a–c
and the final products 4a–u were thoroughly characterized
1
by analyzing their spectral (IR, H NMR, 13C NMR) as
well as elemental analysis data.
© 2012 HeteroCorporation

May 2012
A Facile Synthesis of Novel Dihydroindeno[1,2-e][1,2,4]triazolo[3,4-b][1,3,4]-
thiadiazines Using HTIB
567
Scheme 1. Synthesis of 3-alkyl/aryl-7/9-methyl-10,10a-dihydroindeno
[1,2-e][1,2,4] triazolo[3,4-b][1,3,4]thiadiazines (4a–u).
Figure 1. Synthetic plan.
CONCLUSIONS
In this article, we synthesized a series of 21 novel 3-alkyl/
aryl-7/9-methyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo
[3,4-b][1,3,4]thiadiazines (4) from the cyclocondensation
between 4/6-methyl-2-tosyloxy-1-indanones (2) and 3-alkyl/
aryl-4-amino-5-mercapto-1,2,4-s-triazoles (3). 4/6-methyl-2-
tosyloxy-1-indanones (2) were readily accessible through
hypervalent iodine oxidation of 4/6-methyl-1-indanones (1)
using HTIB.
EXPERIMENTAL
Melting points were taken on slides in an electrical apparatus
Labindia visual melting range apparatus and are uncorrected. IR
spectra were recorded on a Perkin-Elmer 1800 FTIR spectropho-
tometer.1HNMR and 13CNMR spectra were recorded on Bruker
300 MHz instrument using TMS as an internal standard. All other
chemicals used as such as were procured from supplier.
Synthesis of 4/6-methyl-2-tosyloxy-1-indanones (2a-c)
Typical procedure. To a stirred solution of 1-indanone (1a, 5g, 38
mmol) in 100-mL acetonitrile, HTIB (16.45g, 41.9 mmol) was
added and the reaction mixture was refluxed for 5 h. After that
excess of acetonitrile was distilled off under reduced pressure and
residual mass was crystallized from ethanol. The product was further
washed with cold ethanol and dried to give pure 2-tosyloxy-1-
indanone (2a, 9.72g, 83%).
C16H14O4S: C, 63.56; H, 4.67. Found: C, 63.54; H, 4.65. The other
derivatives 2b–c were synthesized by adopting the similar procedure.
6-Methyl-2-tosyloxy-1-indanone (2b). Light brown; mp
113–114ꢀC; yield 81%; IR (nmax, cmÀ1): 1728 (C O), 1597,
2-Tosyloxy-1-indanone (2a).
Dark brown; mp 110–111ꢀC;
yield 83%; IR (nmax, cmÀ1): 1728(C O), 1597, 1466, 1404, 1373,
1
1489, 1427, 1381, 1281, 1180, 1065; HNMR (d, CDCl3, 300
1
1296, 1188, 1057; HNMR (d, CDCl3, 300 MHz, ppm): 2.484
MHz, ppm): 2.402 (s, 3H, CH3), 2.485 (s, 3H, CH3), 3.192–3.262
(dd, 1H, J1 = 3.9 Hz, J2 = 16.8 Hz), 3.578–3.661 (d, 1H, J2 = 16.8
Hz, J3 = 7.8 Hz), 5.107–5.148 (m, 1H), 7.317–7.344 (d, 1H,
J = 8.1 Hz), 7.389–7.416 (d, 2H, J = 8.1 Hz), 7.469–7.541
(m, 2H), 7.927–7.954 (d, 2H, J = 8.1 Hz); 13CNMR: 21.14
(CH3), 21.74 (CH3), 33.58, 78.57, 124.55, 126.34, 128.23,
129.88, 133.71, 137.63, 138.57, 145.17, 147.30, 197.62
(CO). Anal. Calcd. for C17H16O4S: C, 64.54; H, 4.67. Found:
(s, 3H, CH3), 3.247–3.320 (dd, 1H, J1 = 4.5Hz, J2 = 17.4 Hz),
3.628–3.712 (dd, 1H, J2 = 17.4 Hz, J3 = 7.8 Hz), 5.127–5.169 (dd, 1H,
J1 = 4.5 Hz, J3 = 7.8 Hz), 7.391–7.462 (m, 4H), 7.642–7.690 (m, 1H),
7.735–7.760 (d, 1H, J = 7.5), 7.929–7.955 (d, 2H, J = 7.8 Hz); 13C
NMR: 21.70, 30.88, 33.89, 124.68, 126.66, 128.21, 128.42, 129.87,
133.28, 133.64, 136.33, 145.19, 149.95, 197.52. Anal. Calcd. for
C, 64.52; H, 4.65.
4-Methyl-2-tosyloxy-1-indanone (2c). Light brown; mp
141–142ꢀC; yield 83%; IR (nmax, cmÀ1): 1728 (C O), 1597,
1489, 1435, 1358, 1281, 1180, 1095; 1HNMR (d, CDCl3,
300 MHz, ppm): 2.352 (s, 3H, CH3), 2.486 (s, 3H, CH3),
3.149–3.221 (dd, 1H, J1 = 4.2Hz, J2 = 17.4 Hz), 3.594–3.678
(d, 1H, J2 = 17.4 Hz, J3 = 7.8 Hz), 5.116–5.157 (dd, 1H, J1 = 4.2 Hz,
J3 = 7.8 Hz), 7.307–7.357 (m, 1H), 7.393–7.420 (d, 2H, J = 8.1 Hz),
Figure 2. Retrosynthetic analysis.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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O. Prakash, D. K. Aneja, D. Wadhwa, R. Kumar, and S. Arora
Vol 49
7.468–7.493 (d, 1H, J = 7.5 Hz), 7.573–7.598 (d, 1H, J = 7.5 Hz);
7.939–7.966 (d, 2H, J = 8.1 Hz) 13CNMR: 17.80, 21.14, 32.75,
78.26, 122.03, 128.25, 128.50, 129.89, 133.12, 133.46, 136.04,
136.83, 145.22, 149.07, 197.94 (CO). Anal. Calcd. for C16H14O4S: C,
64.54; H, 4.67. Found: C, 65.53; H, 4.64.
(m, 3H, CH3), 1.886 (m, 2H, CH2), 2.975 (m, 2H, CH2), 3.127–3.160
(m, 1H), 3.696 (m, 1H), 4.166(m, 1H), 7.475–7.578 (m, 3H), 7.980
(m, 1H); 13C NMR: 13.84, 20.48, 26.57, 34.94, 36.29, 123.56,
125.80, 128.52, 133.52, 133.58, 139.32, 147.43, 154.26, 162.61. Anal.
Calcd. for C14H14N4S: C, 62.20; H, 5.22; N, 20.72. Found: C, 62.17;
Synthesis of 3-alkyl/aryl-7/9-methyl-10,10a-dihydroindeno
[1,2-e][1,2,4]triazolo [3,4–b][1,3,4] thiadiazines (4a–u).
Typical procedure. To a solution of 2a (1g, 3.31mmol) in 30
ml ethanol was added equimolar amount of 4-amino-5-mercapto-
1,2,4-triazole (3a, 0.384g) and the reaction mixture was refluxed for
4–5 h. After that the reaction mixture was poured into crushed ice
(100 g), followed by basification with ammonia solution. The solid
product thus obtained was filtered, washed with water, and
recrystalized from aqueous ethanol to give pure 10,10a-dihydroindeno
H, 5.18; N, 20.69.
3-Isopropyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo
[3,4–b][1,3,4] thiadiazine (4e). MP 114–115ꢀC; yield 70%;
IR (nmax, cmÀ1): 1713, 1605, 1520, 1458, 1389, 1304, 1196, 1157,
1
1095; H NMR (d, CDCl3, 300 MHz, ppm): 1.402–1.426 (d, 3H,
CH3), 1.491–1.502 (d, 3H, CH3), 3.086–3.161 (dd, 1H, J1 = 5.4 Hz,
J2 = 17.1 Hz), 3.378–3.448 (m, 1H), 3.662–3.746 (m, 1H),
4.149–4.195 (dd, 1H, J1 = 5.4 Hz, J3 = 8.4 Hz), 7.415–7.489
(m, 2H), 7.560–7.585 (d, 1H, J = 7.5 Hz), 7.951–7.976 (d, 1H,
J = 7.5 Hz); 13C NMR: 19.79, 20.81, 25.50, 34.95, 36.21,
123.52, 125.83, 128.52, 133.31, 133.60, 139.63, 147.47,
158.40, 162.11. Anal. Calcd. for C14H14N4S: C, 62.20; H, 5.22;
N, 20.72. Found: C, 62.18; H, 5.18; N, 20.66.
[1,2-e][1,2,4]triazolo[3,4-b][1,3,4]thiadiazine (4a, 0.67g, 90%).
10,10a-Dihydroindeno[1,2-e][1,2,4]triazolo[3,4–b][1,3,4]
thiadiazine (4a). MP 215–216ꢀC; yield 90%; IR (nmax, cmÀ1): 1682,
1628, 1605, 1481, 1443, 1366, 1304, 1281, 1287, 1188, 1157, 1095;
1HNMR (d, CDCl3, 300 MHz, ppm): 3.026–3.193 (m, 1H),
3.731 (m, 1H), 4.398–4.414 (m, 1H), 7.494–7.601 (m, 3H),
7.954 (m, 1H), 8.758 (s, 1H); 13CNMR: 35.06, 37.01, 123.67,
125.85, 128.72, 132.92, 133.90, 147.56, 163.15. Anal. Calcd.
for C11H8N4S: C, 57.88; H, 3.53; N, 24.54. Found: C, 57.80; H,
3.50; N, 24.44. All other derivatives 4a–u, with the exception of
4k were synthesized by adopting the similar procedure.
In the case of 4k, after pouring the reaction mixture into
crushed ice and basification with ammonia solution, the aqueous
mixture was extracted with dichloromethane (3 Â 50 mL) and
the combined organic layer was dried over anhydrous sodium
sulphate. Finally, solvent was removed by distillation and residual
mass was obtained, which solidified on standing for 2–3 days. 1H
NMR showed that the compound was satisfactorily pure.
3-Phenyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo[3,4–b]
[1,3,4] thiadiazine (4f). MP 214–215ꢀC; yield 88%; IR (nmax, cmÀ1):
1597, 1466, 1366, 1296, 1196, 1165, 1103, 1072, 1026; 1H
NMR (d, CDCl3, 300 MHz, ppm): 3.163–3.220 (m, 1H),
3.731–3.815 (dd, 1H, J1 = 8.1Hz, J2 = 17.1Hz), 4.232 (bs, 1H),
7.489–7.612 (m, 6H); 7.992–8.015(m, 1H), 8.209(m, 2H); 13C
NMR: 34.98, 35.86, 123.78, 125.87, 126.21, 128.25, 128.57,
128.61, 130.23, 133.21, 133.81, 140.97, 147.63, 152.18, 163.05.
Anal. Calcd. for C17H12N4S: C, 67.08; H, 3.97; N, 18.41. Found:
C, 67.02; H, 3.93; N, 18.38.
3-(p-Tolyl)-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo[3,4–b]
[1,3,4] thiadiazine (4g). MP 115–116ꢀC; yield %; IR (nmax, cmÀ1):
1705, 1605, 1458, 1350, 1296, 1157, 1065, 1018; 1H NMR
(d, CDCl3, 300 MHz, ppm): 2.438 (s, 3H, CH3), 3.161–3.206
(m, 1H), 3.755 (bs, 1H), 4.233 (bs, 1H), 6.785–8.097 (m, 8H);
13C NMR: 21.53, 34.98, 35.84, 123.10, 123.78, 125.86, 126.42,
128.28, 128.60, 129.35, 129.80, 133.20, 133.81, 140.06, 140.91,
142.93, 147.63, 152.32. Anal. Calcd. for C18H14N4S: C, 67.90; H,
4.43; N, 17.60. Found: C, 67.86; H, 4.41; N, 17.55.
3-Methyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo[3,4–b]
[1,3,4] thiadiazine (4b). MP 154–155ꢀC; yield 92%; IR (nmax
,
cmÀ1): 1612, 1535, 1466, 1435, 1373, 1304, 1203, 1149, 1095;
1H NMR (d, CDCl3, 300 MHz, ppm): 2.633 (s, 3H, CH3),
3.127–3.177 (m, 1H), 3.705–3.759 (m, 1H), 4.163 (bs, 1H),
7.489–7.599 (m, 3H), 7.981 (bs, 1H); 13C NMR: 18.40, 34.95,
36.28, 123.57, 125.80, 128.53, 133.33, 133.57, 147.42. Anal.
Calcd. for C12H10N4S: C, 59.48; H, 4.16; N, 23.12. Found: C,
57.44; H, 4.10; N, 23.10.
7-Methyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo[3,4-b]
[1,3,4]thiadiazine (4h). MP 208–209ꢀC; yield 78%; IR (nmax
,
cmÀ1): 1612, 1481, 1443, 1358, 1288, 1234, 1188, 1149, 1034;
1H NMR (d, CDCl3, 300 MHz, ppm): 2.480 (s, 3H, CH3),
3.117–3.188 (dd, 1H, J1 = 4.5 Hz, J2 = 16.8 Hz), 3.728–3.811
(dd, 1H, J2 = 16.8 Hz, J3 = 8.1 Hz), 4.560 (bs, 1H), 7.361–7.388
(d, 1H, J = 8.1 Hz), 7.467–7.492 (d, 1H, J = 8.1 Hz), 7.786 (s, 1H),
8.918 (s, 1H); 13C NMR: 21.28, 34.77, 37.20, 123.78, 125.57,
135.53, 139.96, 142.35, 146.62, 163.62. Anal. Calcd. for C12H10N4S:
3-Ethyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo[3,4–b]
[1,3,4] thiadiazine (4c). MP 115–116ꢀC; yield 90%; IR (nmax
,
cmÀ1): 1713, 1605, 1528, 1458, 1381, 1311, 1273, 1188, 1157,
1095; 1H NMR (d, CDCl3, 300 MHz, ppm): 1.431–1.481 (t, 3H,
CH3), 2.946–3.193 (m, 3H), 3.677–3.763 (dd, 1H, J1 = 8.4 Hz,
J2 = 17.4 Hz), 4.153–4.243 (m, 1H), 7.496 (m, 2H), 7.580–7.627
(m, 1H), 7.979–8.005(d, 1H, J = 7.8Hz); 13C NMR: 11.30, 18.40,
34.95, 36.28, 123.57, 125.80, 128.53, 133.33, 133.57, 147.42. Anal.
Calcd. for C13H12N4S: C, 60.91; H, 4.72; N, 21.86. Found: C,
60.88; H, 4.67; N, 21.78.
C, 59.48; H, 4.16; N, 23.12. Found: C, 59.44; H, 4.10; N, 23.09.
3-Methyl-7-methyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo
[3,4-b][1,3,4] thiadiazine (4i). MP 233–234ꢀC; yield 80%; IR
(nmax, cmÀ1): 1582, 1535, 1466, 1373, 1311, 1257, 1219, 1188, 1149,
1041; 1H NMR (d, CDCl3, 300 MHz, ppm): 2.467(s, 3H, CH3),
2.627 (s, 3H, CH3), 3.047–3.122 (dd, 1H, J1 = 5.7 Hz, J2 = 16.8 Hz),
3.620–3.704 (dd, 1H, J2 = 16.8 Hz, J3 = 8.4 Hz), 4.117–4.163 (dd,
1H, J1 = 5.7 Hz, J3 = 8.4 Hz), 7.341–7.7.368 (d, 1H, J = 7.4 Hz),
7.397–7.423 (d, 1H, J = 7.4 Hz), 7.784 (s, 1H) ; 13C NMR: 10.36,
3-Propyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo[3,4–b]
[1,3,4] thiadiazine (4d). MP 129–130ꢀC; yield 85%; IR (nmax
,
cmÀ1): 1713, 1605,1528, 1458, 1389, 1311, 1265, 1196, 1149,
1
1095, 1057, 1026; H NMR (d, CDCl3, 300 MHz, ppm): 1.069
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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A Facile Synthesis of Novel Dihydroindeno[1,2-e][1,2,4]triazolo[3,4-b][1,3,4]-
thiadiazines Using HTIB
569
9-Methyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo[3,4-b]
21.28, 34.59, 36.56, 123.55, 125.49, 133.28, 134.94, 138.71, 139.49,
144.81, 151.00, 162.56. Anal. Calcd. for C13H12N4S: C, 60.91; H,
4.72; N, 21.86. Found: C, 60.88; H, 4.68; N, 21.81.
[1,3,4]thiadiazine (4o). MP 207–208ꢀC; yield 89%; IR (nmax, cmÀ1):
1597, 1481, 1443, 1373, 1288, 1149, 1065, 1034; 1H NMR (d, CDCl3,
300 MHz, ppm): 2.377 (s, 3H, CH3), 3.005–3.137 (m, 1H), 3.612–
3.696 (dd, 1H, J = 8.1 Hz, J = 16.5 Hz), 4.207–4.250 (m, 1H),
7.312–7.415 (m, 2H), 7.620–7.777 (bs, 1H), 8.637 (s, 1H); 13C NMR:
18.35, 33.92, 36.91, 121.01, 128.97, 132.60, 134.48, 135.44, 139.96,
142.25, 146.72, 163.80. Anal. Calcd. for C12H10N4S: C, 59.48;
H, 4.16; N, 23.12. Found: C, 59.44; H, 4.10; N, 23.08.
3-Ethyl-7-methyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo[3,4-b]
[1,3,4] thiadiazine (4j). MP 180–181ꢀC; yield 88%; IR (nmax, cmÀ1):
1666, 1612, 1528, 1466, 1389, 1311, 1257, 1188, 1149, 1119, 1057,
1
1003; H NMR (d, CDCl3, 300 MHz, ppm): 2.474 (s, 3H, CH3),
2.868 (bs, 3H), 3.011–3.125 (m, 3H), 3.659–3.738 (dd, 1H, J =7.2
Hz, J = 16.5 Hz), 4.287 (bs, 1H), 7.356–7.444 (m, 2H), 7.785 (s, 1H);
13C NMR: 11.21, 21.30, 34.69, 36.50, 123.78, 125.57, 135.53. Anal.
Calcd. for C14H14N4S: C, 62.20; H, 5.22; N, 20.72. Found: C, 62.15;
H, 5.16; N, 20.68.
3-Methyl-9-methyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo
[3,4-b][1,3,4] thiadiazine (4p).
MP 219–220ꢀC; yield 91%; IR
(nmax, cmÀ1): 1597, 1535, 1458, 1373, 1311, 1203, 1057; 1H NMR
(d, CDCl3, 300 MHz, ppm): 2.380 (s, 3H, CH3), 2.636 (s, 3H,
CH3), 2.979–3.053 (dd, 1H, J1 = 5.4 Hz, J2 = 16.8 Hz),
3.605–3.690 (dd, 1H, J2 = 16.8 Hz, J3 = 8.4 Hz), 4.138–4.184
(dd, 1H, J1 = 5.4 Hz, J3 = 8.4 Hz), 7.398–7.412 (m, 2H),
7.80–7.85 (m, 1H) ; 13C NMR: 9.80, 17.85, 33.18, 35.64, 120.25,
128.24, 132.34, 133.68, 134.96, 138.81, 146.56, 150.10, 162.97.
Anal. Calcd. for C13H12N4S: C, 60.91; H, 4.72; N, 21.86. Found:
C, 60.85; H, 4.67; N, 21.77.
3-Propyl-7-methyl-10,10a-dihydroindeno[1,2-e][1,2,4]
triazolo[3,4-b][1,3,4] thiadiazine (4k). Semisolid; yield 67%; IR
(nmax, cmÀ1): 1612, 1582, 1528, 1458, 1389, 1281, 1219, 1180,
1
1119, 1034; H NMR (d, CDCl3, 300 MHz, ppm): 1.050–1.098
(t, 3H, CH3, J = 7.2 Hz), 1.838–1.938 (sextet, 2H, CH2), 2.475
(s, 3H, CH3), 2.931–3.122 (m, 3H), 3.624–3.707 (dd, 1H, J = 8.1 Hz,
J = 16.8 Hz), 4.140–4.187 (dd, 1H, J = 5.7 Hz, J = 8.4 Hz),
7.343–7.425 (d, 1H, J = 8.1 Hz), 7.665–7.692 (d, 1H, J = 8.1 Hz),
7.781 (s, 1H); 13C NMR: 13.88, 20.48, 21.28, 26.52, 34.61, 36.51,
123.55, 125.50, 125.92, 128.54, 133.29, 134.98, 138.71, 144.85,
154.22, 162.59. Anal. Calcd. for C15H16N4S: C, 63.35; H, 5.67;
3-Ethyl-9-methyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo
[3,4-b][1,3,4]thiadiazine (4q). MP 223–225ꢀC; yield 93%; IR
(nmax, cmÀ1): 1636, 1597, 1528, 1458, 1381, 1350, 1311 1281,
1203, 1165, 1065, 1034; 1H NMR (d, CDCl3, 300 MHz, ppm):
1.421–1.470 (t, 3H, CH3), 2.376 (s, 3H, CH3), 2.910–3.131 (m,
3H), 3.598–3.683 (dd, 1H, J1 = 8.4 Hz, J2 = 17.1 Hz), 4.145–
4.190 (m, 1H), 7.390–7.403 (m, 2H), 7.799–7.825 (m, 1H); 13C
NMR: 11.30, 18.35, 18.41, 33.81, 36.20, 120.92, 128.82, 133.06,
134.13, 135.35, 139.50, 146.51, 155.30, 162.70. Anal. Calcd. for
C14H14N4S: C, 62.20; H, 5.22; N, 20.72. Found: C, 62.16; H, 5.18;
N, 20.68.
N, 19.70. Found: C, 63.31; H, 5.61; N, 19.66.
3-Isopropyll-7-methyl-10,10a-dihydroindeno[1,2-e][1,2,4]
triazolo[3,4-b][1,3,4]thiadiazine (4l). MP 150–151ꢀC; yield
69%; IR (nmax, cmÀ1): 1612, 1520, 1458, 1389, 1311, 1281, 1196,
1157, 1095, 1034; 1H NMR (d, CDCl3, 300 MHz, ppm):
1.411–1.434 (d, 3H, CH3), 1.497–1.520 (d, 3H, CH3), 2.455
(s, 3H, CH3), 3.026–3.100 (dd, 1H, J1 = 5.4 Hz, J2 = 16.8 Hz),
3.373–3.488 (m, 1H), 3.620–3.704 (dd, 1H, J2 = 16.8 Hz, J3 = 8.4
Hz), 4.159–4.205 (m, 1H), 7.331–7.412 (m, 2H), 7.752 (s, 1H); 13C
NMR: 20.29, 21.05, 21.26, 25.49, 34.63, 36.45, 123.49, 125.33, 133.25,
135.04, 138.70, 139.92, 144.93, 158.27, 162.60. Anal. Calcd. for
3-Propyl-9-methyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo
[3,4-b][1,3,4]thiadiazine (4r). MP 80–81ꢀC; yield 89%; IR
(nmax, cmÀ1): 1597, 1520, 1458, 1389, 1342, 1304, 1273, 1203,
1
1034; H NMR (d, CDCl3, 300 MHz, ppm): 0.912–1.102 (m, 3H,
C15H16N4S: C, 63.35; H, 5.67; N, 19.70. Found: C, 63.30; H, 5.64; N, 19.68.
3-Phenyl-7-methyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo
[3,4-b][1,3,4] thiadiazine (4m). MP 218–219ꢀC; yield 79%; IR
CH3), 1.801–1.928 (m, 2H, CH2), 2.245 (s, 3H, CH3), 2.910–3.101
(m, 3H), 3.510–3.720 (m, 1H), 4.201–4.230 (m, 1H), 7.293–7.800
(m, 3H); 13C NMR: 13.86, 18.36, 20.43, 26.45, 33.85, 36.19,
121.01, 128.85, 132.88, 134.35, 135.42, 139.77, 146.70, 163.42.
Anal. Calcd. for C15H16N4S: C, 63.35; H, 5.67; N, 19.70. Found:
C, 63.30; H, 5.64; N, 19.65.
3-Isopropyl-9-methyl-10,10a-dihydroindeno[1,2-e][1,2,4]
triazolo[3,4-b][1,3,4]thiadiazine (4s). MP 187–188ꢀC; yield 86%; IR
(nmax, cmÀ1):1597, 1520, 1458, 1389, 1350, 1311, 1281, 1203, 1157,
1095, 1065, 1034; 1H NMR (d, CDCl3, 300 MHz, ppm): 1.501–1.60
(m, 6H), 2.865 (s, 3H), 2.969–3.025 (m, 1H), 3.450–3.682 (m, 2H),
4.217 (bs, 1H), 7.293–7.800 (m, 3H); 13C NMR: 18.35, 19.77, 20.80,
25.49, 33.83, 36.13, 120.89, 128.81, 133.01, 134.19, 135.38, 139.76,
146.60, 158.32, 162.76. Anal. Calcd. for C15H16N4S: C, 63.35;
H, 6.67; N, 19.70. Found: C, 63.28; H, 6.62; N, 19.65.
(nmax, cmÀ1): 1612, 1574, 1458, 1373, 1304, 1219, 1180, 1149, 1119,
1
1080, 1041, 1011; H NMR (d, CDCl3, 300 MHz, ppm): 2.475
(s, 3H, CH3), 3.091–3.164 (dd, 1H, J1 = 4.8 Hz, J2 = 16.8 Hz),
3.679–3.763 (dd, 1H, J2 = 16.8 Hz, J3 = 8.4 Hz), 4.191–4.236
(m, 1H), 7.363–7.441 (m, 2H), 7.543–7.564 (m, 3H), 7.784 (s, 1H),
8.194–8.213 (m, 2H); 13C NMR: 21.28, 34.64, 36.10, 123.69,
125.55, 126.18, 128.27, 128.61, 130.24, 135.16, 138.80, 141.14,
145.00, 163.22. Anal. Calcd. for C18H14N4S: C, 67.90; H, 4.43;
N, 17.60. Found: C, 67.85; H, 4.39; N, 17.56.
3-(p-Tolyl)-7-methyl-10,10a-dihydroindeno[1,2-e][1,2,4]
triazolo[3,4-b][1,3,4] thiadiazine (4n). MP 150–151ꢀC; yield 83%;
IR (nmax, cmÀ1): 1612, 1489, 1458, 1350, 1288, 1173, 1119, 1065,
1011; 1H NMR (d, CDCl3, 300 MHz, ppm): 2.419 (s, 6H, CH3 Â 2),
3.129–3.393 (m, 1H), 3.571–3.852 (m, 1H), 4.583 (bs, 1H), 7.100
(m, 1H), 7.266–8.071 (m, 8H); 13C NMR: 21.14, 21.71, 34.66, 36.01,
125.58, 126.43, 128.23, 128.49, 129.48, 129.83, 142.98, 145.16. Anal.
Calcd. for C19H16N4S: C, 68.65; H, 4.85; N, 16.85. Found: C, 68.54;
H, 4.78; N, 16.78.
3-Phenyl-9-methyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo
[3,4-b][1,3,4]thiadiazine (4t). MP 255ꢀC (dec); yield 79%; IR
(nmax, cmÀ1): 1597, 1528, 1458, 1373, 1304, 1203, 1119, 1034;
1H NMR (d, CDCl3, 300 MHz, ppm): 2.384 (s, 3H, CH3), 3.019–
3.070 (m, 1H), 3.687 (bs, 1H), 4.274 (bs, 1H), 7.441–8.612
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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O. Prakash, D. K. Aneja, D. Wadhwa, R. Kumar, and S. Arora
Vol 49
(m, 8H); 13C NMR: 18.39, 33.91, 35.79, 121.15, 128.23,
128.57, 128.90, 130.22, 132.96, 134.35. Anal. Calcd. for
[9] El-Dawy, M. A., Omar, A. M. M. E.; AbM. Ismail, Hazzaa, A. A. B.
J Pharm Sci 1983, 72, 45.
[10] Holla, B. S.; Kalluraya, B. Indian J Chem Sect B 1988, 27, 683.
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C
18H14N4S: C, 67.90; H, 4.43; N, 17.60. Found: C, 67.84;
H, 4.40; N, 17.56.
[12] Dhaka, K. S.; Mohan, J.; Chadha, V. K.; Pujari, H. K. Indian J
Chem 1974, 12, 287.
3-(P-tolyl)-9-methyl-10,10a-dihydroindeno[1,2-e][1,2,4]triazolo
[3,4-b][1,3,4]thiadiazine (4u). MP 290–291ꢀC; yield 76%; IR
[13] (a) Prakash, O.; Saini, N.; Tanwar, M. P.; Moriarty, R.M. Con-
temp Org Synth 1995, 2, 121; (b) Moriarty, R. M.; Prakash, O. Org React
1999, 54, 273 (c) Prakash, O.; Saini, N.; Sharma, P. K. Heterocycles 1994,
38, 409; (d) Prakash, O.; Saini, N.; Sharma, P. K. Synlett 1994, 221; (e)
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R. M.; Prakash, O. Adv Heterocycl Chem 1998, 69, 1.
1
(nmax, cmÀ1):1597, 1450, 1366, 1304, 1180, 1111, 1034; H NMR
(d, CDCl3, 300 MHz, ppm): 2.392 (s, 3H, CH3), 2.461 (s, 3H, CH3),
3.018–3.074 (m, 1H), 3.665–3.746 (dd, 1H, J1 = 16.8 Hz, J2 = 6.9
Hz), 4.263 (bs, 1H), 7.342–7.368 (d, 2H, J = 7.8 Hz), 7.417 (bs, 2H),
7.825 (bs, 1H), 8.099–8.124 (d, 2H, J = 7.8 Hz); 13C NMR: 18.38,
21.56, 33.90, 35.78, 121.12, 128.21, 128.88, 129.32, 132.99, 134.33,
135.43, 140.56, 146.71, 163.51. Anal. Calcd. for C19H16N4S: C,
68.65; H, 4.85; N, 16.85. Found: C, 68.60; H, 4.79; N, 16.80.
[14] (a) Singh, S. P.; Nathani, R.; Aggarwal, R.; Prakash, O. Synth
Comm 1998, 28, 3133; (b) Kumar, R; Nair, R. R.; Dhiman, S. S.; Sharma,
J.; Prakash, O. Med Chem Res 2010, 19, 541; (c) Kumar, R; Nair, R. R.;
Dhiman, S. S.; Sharma, J.; Prakash, O. Eur J Med Chem 2009, 44, 560;
(d) Prakash, O.; Kumar, R.; Sehrawat, R. Eur J Med Chem 2009, 44,
1763; (e) Prakash, O.; Kumar, R.; Sehrawat, R. Eur J Med Chem 2008,
43, 435; (f) Prakash, O.; Kumar, R.; Sharma, D.; Pannu, K.; Kamal, R.
Synlett 2007, 14, 2189 (g) Prakash, O.; Kumar, R.; Kumar, R.; Tyagi, P.;
Kuhad, R. C. Eur J Med Chem 2007, 42, 868; (h) Prakash, O.; Pannu, K.
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Prakash, O.; Saini, N.; Sharma, P. K. J Chem Res (S) 1993, 430; (k)
Prakash, O.; Saini, N. Synth Commun 1993, 23, 1455 (l) Moriarty, R. M.;
Vaid, R. K.; Hopkins, T. E.; Vaid, B. K.; Prakash, O. Tetrahedron lett 1990,
31, 201; (m) Prakash, O.; Saini, N.; Goyal, S. J Chem Soc Perkin Trans I
1992, 701; (n) Prakash, O.; Pannu, K.; Prakash, R.; Batra, A. Molecules
2006, 11, 543.
Acknowledgments. We are thankful to Council of Scientific and
Industrial Research (CSIR 01(2186)/ 07/ EMR-II), New Delhi for
providing financial assistance to carry out this work. One of the
author Deepak Kumar Aneja is grateful to the Haryana State
Counseling Society, Panchkula (Haryana), India for providing
Sir C. V. Raman Research Scholarship for financial support.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet