New Route for the Synthesis of Thiazolidine 2,4dione Azepine Derivatives

Article abstract of DOI:10.1002/jhet.2676

A new facile ionic liquid mediated proficient method is developed for the synthesis of structurally new thiazepine and oxazepine derivatives of thiazolidine 2,4-dione. This protocol proceeds through, one-pot three component reaction between fused cyclic k

Full text of DOI:10.1002/jhet.2676

Month 2016 New Route for the Synthesis of Thiazolidine 2,4dione Azepine Derivatives
*
Devendar Reddy Kommidi, Ramakanth Pagadala, Mohan Varkolu, Neil A. Koorbanally, and Brenda Moodley
School of Chemisry and Physics, University of KwaZulu-Natal, Wesvile, Durban, South Africa, 4000
*
E-mail: kdreddy9925@gmail.com
Additional Supporting Information may be found in the online version of this article.
Received September 30, 2015
DOI 10.1002/jhet.2676
Published online 00 Month 2016 in Wiley Online Library (wileyonlinelibrary.com).
A new facile ionic liquid mediated proficient method is developed for the synthesis of structurally new
thiazepine and oxazepine derivatives of thiazolidine 2,4-dione. This protocol proceeds through, one-pot
three component reaction between fused cyclic ketone, substituted aromatic aldehyde, 2-amino phenol and
2-amino thiobenzene at room temperature to yield structurally new derivatives.
J. Heterocyclic Chem., 00, 00 (2016).
INTRODUCTION
[21]. Versatile physical properties like separation of the
product, increase in the rate of reaction, catalyst immobili-
sation [22–32] made ionic liquids an inseparable part of
much organic synthesis [33–42]. In recent times, room
temperature ionic liquids have received a lot of attention
as green and desirable solvents due to their low volatile
nature [43–45]. Regardless of having many synthetic
methods available for thiaze and oxazepines, developing
multicomponent synthetic strategy with operational
simplicity, eco-friendly nature and cost effective is
always a challenging one. In continuation of our efforts
to develop an eco-friendly MCRS, we unfold a [bmim]
BF4 mediated multicomponent protocol for the synthesis
of thiazepines and oxazepines of thiazolidine 2,4 dionehere.
Though there are reports on synthesis of different
thiazapines and Oxazapines, our protocol for the synthesis
of structurally new thiaze and oxazepinesof thiazolidine 2,
4 dione in a green manner is a new one Tables 1 and 2.
Desired products are being made through one-pot
multicomponent reactions (MCRs) as MCRs are time and
cost effective. These features make multicomponent
reactions fighting fit for the quick assembly of molecules
to get desired products in one pot procedure [1–10].
Heterocyclics are prevalent building blocks in medicinal
chemistry particularly thiazepines and oxazepines due to
their broad spectral biological activities like antifeedant,
analgesic, anticonvulsant, calcium antagonism, antibacte-
rial, anti-anginal, anti-HIV, squalenesynthetase inhibition,
V2 arginine vasopressin receptor antagonism15 and
HIV-1 reverse transcriptase inhibition [11–20]. Develop-
ing a new MCR strategy is always a challenging job not
only because of the reactivity of starting materials but
also the reactivity, Compatibility and compartmentaliza-
tion of the intermediates generated in situ in the reaction
© 2016 Wiley Periodicals, Inc.

D. R. Kommidi, R. Pagadala, M. Varkolu, N. A. Koorbanally, and B. Moodley
Vol 000
Table 1
DCM and ethanol. Standardisation of the protocol with
different catalysts in different solvents revealed that,
though the product is formed with catalysts like
CH3COOH, TCS in solvents DCM and ethanol, the yield
was low with high reaction time; with AlCl3 as catalyst
in ethanol gave good yield (85% table No 1 entry 15)
with 18hrs reaction time. In continuation of previous
efforts to develop and eco-friendly protocol with less
reaction time, we then employed an ionic liquid [bmim]
BF4 because of its high polar, non-coordinating and
increasing the nucleophilic strength nature. Moreover with
the presence of [bmim]BF4 no Lewis acid or special
activation energy is needed [48]. The employment of
[bmim]BF4 as a catalyst and as well as the solvent not
only produced high yields(93% Table No 1 entry 16)
but also reduced the reaction time to 7hrs. The present
synthesis is even optimized by multistep and one-pot,
initially substituted aryl aldehyde was added to
thiazoilidine 2, 4 dione and allowed to stir for one hour
and later added ortho-substituted aniline; this approach
did not yield the desired product. When one-pot method
was used i.e all the reactants were dissolved in [bmim]
BF4 at once and allowed the reaction to continue it yielded
desired products. This proves that one-pot method is
suitable for the synthesis of oxazepine and thiazepine
derivatives [49].
Optimisation of reaction conditions.
Entry
Solvent
Toluene
Catalyst
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
CH3COOH
TCS
TEA
PTSA
AlCl3
CH3COOH
TCS
TEA
PTSA
AlCl3
CH3COOH
TCS
TEA
PTSA
18
18
18
18
18
18
18
18
18
18
18
18
18
18
18
7
b
b
b
b
5
30
42
20
b
60
32
45
7
DCM
Ethanol
9
10
11
12
13
14
15
16
b
85
93
AlCl3
[bmim] BF4
[bmim] BF4
*b: no reaction
Table 2
Results of synthesized derivatives.
Entry
Compound
R
Yield (%)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4 g
4 h
4i
H
4-NO2
4-Br
93
95
94
93
91
95
92
90
96
88
94
89
92
92
91
93
87
96
94
91
4-Cl
4-OCH3
4-Dimethyl amino
2-OCH3
2-NO2
2, 4 Dichloro
Vera
9
10
11
12
13
14
15
16
17
18
19
20
4j
Schematic representation of the synthesis. The reaction
was possibly facilitated by the strong alkylating, highly
polar, dehydrating, non-coordinating and in situ
transformation natures of the [bmim]BF4 [50], the
proposed mechanism show that the dehydration formed
the final derivatives. The hydrophilic nature of the
[bmim]BF4 might have facilitated the dehydration the
previous reports show that hydrophilic ionic liquids pave
the way for dehydration [51]. After optimizing the
reaction conditions, the scope of the protocol was
successfully expanded for the synthesis of azepine
derivatives of thiazolidinedione by with substituted
aldehydes and ortho substituted aniline.
Synthesized compounds were characterized by spectral
(IR, 1H, 13C NMR and mass) and elemental analysis,
where appropriate. The presence of –NH2 group in product
structure was confirmed by 15N NMR (GHSQC) (ESI).
The doublet at δ 6.58 revealed the presence of CH-S in
the products. Characteristic signals at 167-170 in 13C
NMR the proved the presence of C = N of the azepine ring
(ESI).
5a
5b
5c
5d
5e
5f
5 g
5 h
5i
H
4-NO2
4-Br
4-Cl
4-OCH3
4-Dimethyl amino
2-OCH3
2-NO2
2, 4 Dichloro
Vera
5j
In analogy to reported protocols for the synthesis of
thiaze and oxazepines [46], we developed new eco-
friendly protocol for the synthesis of structurally new
thizolidine 2,
4
dione thiazepine and oxazepine
derivatives. The literature review suggested that slightly
acidic conditions favour the formation of the azepines
[47]. The ideal reaction condition was augmented by
comparing different catalysts CH3COOH, TCS, TEA,
PTSA and AlCl3. All these reactions were carried out at
room temperature in different solvents like toluene,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
New Route for the Synthesis of Thiazolidine 2,4dione Azepine Derivatives
Mechanism.
Compound 4b. 10-(4-Nitro-phenyl)-10,10a-dihydro-3H-1,9-
dithia-3,4-diaza-benzo[f]azulen-2-one.
Off-white solid:
mp 190-191°C; H NMR (400MHz, DMSO-d6) δ =6.89
(1H, d, J= 9.1), 6.73 (1H, d, J=9.5Hz), 7.75 (1H, s, NH),
8.13 (2H, d, J= 9.4 Hz), 8.20 (2H, d, J=9.2Hz), 8.34-8.40
(4H, m); 13C NMR (100MHz, DMSO-d6): δ 40.24, 54.22,
122.25, 123.02, 123.96, 124.74, 124.96, 126.81, 127.54,
149.38, 150.11, 154.04, 165.30; IR (cm-1): 1033-1288 (C-
S), 1344 (Ph-NO2), 1569 (C =N), 1657 (C = O), 3345
(NH); MS (ESI), m/z =380 (M + Na, 100%); Anal. Calcd
(C16H11N3O3S2): C 53.77, H 3.10, N 11.76%. Found: C
53.78, H 3.11, N 11.77%.
1
Compound 4c. 10-(4-Bromo-phenyl)-10,10a-dihydro-3H-
1,9-dithia-3,4-diaza-benzo[f]azulen-2-one.
Off-white
solid: mp 187-188°C; 1H NMR (400MHz, DMSO-d6)
δ= 6.40 (1H, d, J = 10.0), 6.59 (1H, d, J = 8.3 Hz), 7.40-
7.58 (4H, m), 7.77 (2H, d, J = 8.5 Hz), 8.03 (1H, s,
NH), 8.06 (2H, d, J = 8.0 Hz); 13C NMR (100 MHz,
DMSO-d6): δ 43.34, 53.55, 122.43, 122.94, 123.34,
124.85, 125.50, 125.75, 126.79, 128.21, 143.38,
153.44, 153.54, 167.26; IR (cm-1): 965 (Ph-Br),
1012-1289 (C-S), 1562 (C = N), 1653 (C = O), 3348
(NH); MS (ESI), m/z = 392 (M + 1, 100%); Anal. Calcd
(C16H11BrN2OS2): C 49.11, H 2.83, N 7.16%. Found:
C 49.13, H 2.84, N 7.17%.
Synthesis of thiazolidine 2, 4 dione. Thiazolidine 2,4dione,
one of the starting materials was prepared as described
elsewhere [52].
Synthesis of thiazepine derivatives of thiazolidine 2, 4
dione. An equimolar amounts of thiazolidine 2,4dione
(1 mmol), substituted aryl aldehydes and 2-amino thia
benzene were taken into a round bottom flask containing
[bmim] BF4, and this mixture was allowed to stir at room
temperature. TLC monitored the progress of the reaction.
Development of the precipitate was observed which
indicated the formation of the product, the obtained
precipitate was filtered off and washed with water to
extract ionic liquid. The solid obtained was recrystallized
from ethanol to obtain pure final product.
Synthesis of oxazapine derivatives of thiazolidine 2, 4
dione. An equimolar amounts of thiazolidine 2,4 dione
(1 mmol), substituted aryl aldehydes (1 mmol) and
2-amino phenol (1mmol)were taken into a round bottom
flask containing [bmim] BF4, this mixture was allowed to
stir at room temperature until the final product is
obtained. The progress of the reaction was monitored by
TLC. The development of precipitate indicated the
formation of final derivative; the obtained precipitate was
filtered off and washed with water to extract ionic liquid.
The solid obtained was recrystallized from ethanol to
obtain pure final product.
Compound 4d. 10-(4-Chloro-phenyl)-10,10a-dihydro-3H-
1,9-dithia-3,4-diaza-benzo[f]azulen-2-one.
Off-white solid:
mp 184-185°C; H NMR (400 MHz, DMSO-d6) δ= 6.42
(1H, d, J = 10.0), 6.58 (1H, d, J = 8.3 Hz), 7.42 -7.59
(4H, m), 7.78 (2H, d, J = 8.5 Hz), 8.01 (1H, s, NH),
8.06 (2H, d, J=8.0Hz); 13C NMR (100MHz, DMSO-d6):
δ 43.44, 54.24, 122.42, 122.94, 125.72, 126.77,
128.85, 129.45, 131.66, 134.54, 135.99, 147.45,
153.44, 165.94; IR (cm-1): 822 (Ph-Cl), 1033-1296
(C-S), 1564 (C = N), 1635 (C = O), 3345 (NH); MS
(ESI), m/z = 369 (M + Na+, 100%); Anal. Calcd
(C16H11ClN2OS2): C 55.40, H 3.20, N 8.08%. Found:
C 55.42, H 3.21, N 8.10%.
1
Compound 4e. 10-(4-Methoxy-phenyl)-10,10a-dihydro-3H-
1,9-dithia-3,4-diaza-benzo[f]azulen-2-one.
Off-white solid:
mp 176-177°C; H NMR (400 MHz, DMSO-d6) δ= 3.85
(3H, s), 6.44 (1H, d, J = 7.7 Hz), 6.60 (1H, d, J = 8.7 Hz),
6.84 -6.94 (4H, m), 7.99 (2H, d, J = 7.9 Hz), 8.05 (1H, s,
NH), 8.09 (2H, d, J = 8.0 Hz); 13C NMR (100 MHz,
DMSO-d6): δ 43.74, 55.09, 64.74, 122.16, 122.43,
125.07, 125.49, 128.58, 126.48, 134.19, 153.63, 159.58,
161.76, 167.01; IR (cm-1): 1026-1292 (C-S), 1583
(C = N), 1652 (C = O), 2852 (Ph-OCH3), 3350 (NH); MS
(ESI), m/z = 365 (M + Na+, 100%); Anal. Calcd
(C17H14N2O2S2): C 59.63, H 4.12, N 8.18%. Found: C
59.65, H 4.13, N 8.19%.
1
Compound 4a. 10-Phenyl-10,10a-dihydro-3H-1,9-dithia-
3,4-diaza-benzo[f]azulen-2-one. Off-white solid: mp 170-
1
171°C; H NMR (400 MHz, DMSO-d6) δ= 6.47 (1H,
d, J= 8.2), 6.56 (1H, d, J = 8.9 Hz), 7.54-757 (4H, m),
8.05 (1H, s, NH), 8.07-8.14 (5H, m); 13C NMR
(100 MHz, DMSO-d6): δ 43.62, 53.08, 122.29, 122.86,
125.50, 126.10, 126.61, 126.77, 127.16, 128.29,
134.43, 147.42, 153.54, 167.26; IR (cm-1): 1024-1294,
1560 (C = N), (C-S), 1656 (C = O), 3346 (NH); MS (ESI),
m/z= 335 (M + Na, 100%); Anal. Calcd (C16H12N2OS2):
C 61.51, H 3.87, N 8.97%. Found: C 61.52, H 3.87,
N 8.98%.
Compound 4f. 10-(4-Dimethylamino-phenyl)-10,10a-dihydro-
3H-1,9-dithia-3,4-diaza-benzo[f]azulen-2-one.
Off-white
solid: mp 182-183°C; 1H NMR (400MHz, DMSO-d6)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

D. R. Kommidi, R. Pagadala, M. Varkolu, N. A. Koorbanally, and B. Moodley
Vol 000
δ= 2.87 (6H, s), 6.40 (1H, d, J = 7.4 Hz), 6.44 (1H, d,
J = 9.2 Hz), 7.30-7.37 (4H, m), 7.87 (2H, d J = 8.96 Hz),
7.91 (2H, d, J = 8.0 Hz), 8.01 ( 1H, s,NH); 13C NMR
(100 MHz, DMSO-d6): δ 43.36, 69.65, 120.08, 121.82,
121.88, 124.39,126.23, 127.20, 128.42, 131.09, 133.77,
135.36, 152.17, 153.88, 167.80, 169.75; IR (cm-1): 963-
1297 (C-S), 1357 (N-CH3), 1562 (C = N), 1632 (C = O),
3346 (NH); MS (ESI), m/z = 356 (M + 1, 100%); Anal.
Calcd (C18H17N3OS2): C 60.82, H 4.82, N 11.81%.
Found: C 60.83, H 4.84, N 11.82%.
J = 8.0 Hz), 7.01-7.05 (4H, m), 7.40 (1H, d, J =8.9Hz),
7.43 (1H, s,), 7.44 (1H, d, J = 8.9 Hz), 8.01 (1H, s, NH);
13C NMR (100 MHz, DMSO-d6): δ 49.42, 55.69, 56.24,
120.88, 122.12, 122.43, 125.09, 125.56, 126.48, 134.28,
149.10, 151.60, 153.57, 167.19; IR (cm-1): 1026-1292
(C-S), 1584 (C =N), 1652 (C =O), 2852 (Ph-OCH3),
3350 (NH); MS (ESI), m/z =395 (M + Na+, 100%); Anal.
Calcd (C18H16N2O3S2): C 58.04, H 4.33, N 7.52%.
Found: C 58.06, H 4.34, N 7.53%.
Compound 5a. 10-Phenyl-10,10a-dihydro-3H-9-oxa-1-thia-
Compound 4 g. 10-(2-Methoxy-phenyl)-10,10a-dihydro-3H-
3,4-diaza-benzo[f]azulen-2-one. Off-white solid: mp 173-
174-183°C; H NMR (400MHz, CDCl3) δ= 6.60 (1H, d,
1
1,9-dithia-3,4-diaza-benzo[f]azulen-2-one.
Off-white solid:
1
mp 192-193°C; H NMR (400 MHz, DMSO-d6) δ = 4.05
(3H, s), 6.95 (1H, d, J = 7.3), 6.97 (1H, d, J = 7.3 Hz),
7.41-7.45 (4H, m), 7.84 (1H, s, NH), 7.86-7.87 (1H, t,
J = 10.2 Hz), 8.04 (1H, d. J = 8.1 Hz), 8.11 (1H, d,
J = 7.84 Hz), 8.27 (1H, d, J = 8.0 Hz); 13C NMR
(100 MHz, DMSO-d6): δ 43.31, 53.96, 56.36, 121.07,
121.76, 122.34, 124.86, 126.22, 128.56, 132.40, 135.31,
156.96, 169.84, 173.81; IR (cm-1): 1026-1292 (C-S),
1583 (C = N), 1652 (C = O), 2852 (Ph-OCH3), 3350
(NH); MS (ESI), m/z = 365 (M + Na+, 100%); Anal.
Calcd (C17H14N2O2S2): C 59.63, H 4.12, N 8.18%.
Found: C 59.65, H 4.13, N 8.19%.
J = 8.6 Hz), 6.62 (1H, d, J = 8.8 Hz), 7.15-7.19 (5H, m),
7.36-7.38 (4H, m), 7.85 (1H, s, NH); 13C NMR
(100 MHz, CDCl3): δ =44.20, 53.01, 115.24, 128.25,
128.77, 128.81, 129.13, 131.61, 135.00, 136.84, 147.29,
148.64, 164.13, 169.78; IR (cm-1): 1075-1164 (C-O),
1597 (C = N), 1661 (C = O), 3408 (NH); MS (ESI),
m/z= 297 (M + 1 100%); Anal. Calcd (C16H12N2O2S2): C
64.85, H 4.08, N 9.45%. Found: C 64.86, H 4.10, N
9.46%.
Compound 5b. 10-(4-Nitro-phenyl)-10,10a-dihydro-3H-9-
oxa-1-thia-3,4-diaza-benzo[f]azulen-2-one.
Off-white
solid: mp 192-193°C; 1H NMR (400MHz, DMSO-d6)
δ= 6.82 (1H, d, J= 8.6), 6.91 (1H, d, J =7.3 Hz), 7.11-
7.16 (4H, m), 8.28 (2H, d, J = 8.8 Hz), 8.33 (2H, d,
J = 8.7 Hz), 8.89 (1H, s, NH); 13C NMR (100MHz,
DMSO-d6): δ= 44.59, 55.97,116.35, 119.30, 119.46,
123.79, 124.23, 128.50, 129.74, 136.88, 148.61, 151.74,
164.99, 169.94; IR (cm-1): 105-1255 (C-O), 1329 (Ph-
NO2), 1557 (C = N), 1652 (C = O), 3395 (NH); MS (ESI),
m/z= 364 (M + Na+, 100%); Anal. Calcd (C16H11N3O4S):
C 56.30, H 3.25, N 12.31%. Found: C 56.32, H 3.28, N
12.32%.
Compound 4 h. 10-(2-Nitro-phenyl)-10,10a-dihydro-3H-
1,9-dithia-3,4-diaza-benzo[f]azulen-2-one.
Off-white solid:
mp 179-180°C; 1H NMR (400 MHz, DMSO-d6)
δ= 6.70 (1H, d, J = 7.0), 6.73 (1H, d, J = 8.7 Hz), 6.99-
7.01 (4H, m), 7.05-7.10 (4H, m), 7.63 (1H, s, NH,
J = 7.9 Hz); 13C NMR (100 MHz, DMSO-d6): δ 43.08,
54.24, 122.76, 123.03, 127.24, 127.85, 127.90, 128.83,
129.46,131.08, 135.37, 147.35, 149.69, 164.50,
169.88; IR (cm-1): 1078-1317 (C-S), 1351 (Ph-NO2),
1594 (C = N), 1657 (C = O), 3385 (NH); MS (ESI),
m/z=380 (M+Na+, 100%); Anal. Calcd (C16H11N3O3S2):
C 53.77, H 3.10, N 11.76%. Found: C 53.78, H 3.12,
N 11.78%.
5C. 10-(4-Bromo-phenyl)-10,10a-dihydro-3H-9-oxa-1-thia-
3,4-diaza-benzo[f]azulen-2-one. Off-white solid: mp 186-
1
187°C; H NMR (400 MHz, DMSO-d6) δ= 6.80 (1H, d,
Compound 4i. 10-(2,4-Dichloro-phenyl)-10,10a-dihydro-
J = 9.1), 6.88 (1H, d, J = 7.2 Hz), 7.07-7.11 (4H, m), 7.70
(2H, d, J =8.4 Hz), 7.96 (2H, d, J = 8.4 Hz), 8.70 (1H, s,
NH); 13C NMR (100MHz, DMSO-d6): δ =51.06, 74.42,
116.07, 124.70, 127.65, 130.65, 131.22, 131.66, 132.28,
135.55, 137.42, 151.27, 157.96, 169.89; 944 (Ph-Br),
1082-1259 (C-O), 1602 (C = N), 1674 (C = O), 3334
(NH); MS (ESI), m/z = 398 (M+ Na+, 100%); Anal. Calcd
(C16H11BrN2O2S): C 51.21, H 2.95, N 7.47%. Found: C
51.31, H 2.97, N 7.67%.
3H-1,9-dithia-3,4-diaza-benzo[f]azulen-2-one.
Off-white
solid: mp 176-177°C; 1H NMR (400 MHz, DMSO-d6)
δ= 6.63 (1H, d, J = 7.3), 6.73 (1H, d, J= 7.6 Hz), 7.57-
7.66 (4H, m), 8.12 (1H, s, NH), 8.14 (1H, s), 8.20 (1H,
d, J= 10.2 Hz), 8.24 (1H, d, J = ); 13C NMR (100MHz,
DMSO-d6): δ 49.48, 51.85, 122.18, 123.14, 125.97,
126.80, 128.13, 130.33, 132.39, 132.77, 135.35, 151.85,
162.24, 169.77; IR (cm-1): 822 (Ph-Cl), 1033-1296 (C-S),
1592 (C =N), 1635 (C = O), 3345 (NH); MS (ESI),
m/z= 380 (M + 1, 100%); Anal. Calcd (C16H10Cl2N2OS2):
C 50.40, H 2.64, N 7.35%. Found: C 50.42, H 2.65,
N 7.34%.
5d. 10-(4-Chloro-phenyl)-10,10a-dihydro-3H-9-oxa-1-thia-
3,4-diaza-benzo[f]azulen-2-one. Off-white solid: mp 189-
1
190°C; H NMR (400 MHz, DMSO-d6) δ=6.51 (1H, d,
J= 9.3), 6.54 (1H, d, J=9.2 Hz), 7.06-7.21 (4H, m), 7.91
(2H, d, J= 8.4 Hz), 8.03 (2H, d, J= 8.5 Hz), 9.07 (1H, s,
NH); 13C NMR (100 MHz, DMSO-d6): δ54.24, 74.70,
116.42, 122.94, 125.72, 126.77, 128.85, 129.45, 131.66,
134.54, 135.99, 147.45, 153.44, 165.94; IR (cm-1): 843
Compound 4j. 10-(2,4-Dimethoxy-phenyl)-10,10a-dihydro-
3H-1,9-dithia-3,4-diaza-benzo[f]azulen-2-one.
Off-white
solid: mp 182-183°C; 1H NMR (400 MHz, DMSO-d6)
δ= 3.89 (6H, s), 6.46 (1H, d, J= 7.8 Hz), 6.61 (1H, d,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

Month 2016
New Route for the Synthesis of Thiazolidine 2,4dione Azepine Derivatives
(Ph-Cl), 1040-1289 (C-O), 1590 (C = N), 1656 (C = O),
3348 (NH); MS (ESI), m/z= 353 (M + Na+, 100%); Anal.
Calcd (C16H11ClN2O2S): C 58.09, H 3.35, N 8.47%.
Found: C 58.11, H 3.37, N 8.49%.
Compound 5i. 10-(2,4-Dichloro-phenyl)-10,10a-dihydro-
3H-9-oxa-1-thia-3,4-diaza-benzo[f]azulen-2-one.
Off-white
solid: mp 178-179°C; 1H NMR (400MHz, DMSO-d6)
δ=6.51 (1H, d, J=7.5), 6.67 (1H, d, J= 7.8 Hz), 7.10-7.23
(4H, m), 7.55-7.57 (3H, m), 7.85 (1H, s, NH); 13C NMR
(100MHz, DMSO-d6): δ 49.48, 51.85, 122.18, 132.14,
125.97, 126.80, 128.13, 130.33, 132.39, 132.77, 135.35,
151.85, 162.24, 169.77822 (Ph-Cl), 1033-1296 (C-S),
1601 (C=N), 1635 (C=O), 3345 (NH); MS (ESI),
m/z=366 (M+1, 100%); Anal. Calcd (C16H10Cl2N2O2S):
C 52.62, H 2.76, N 19.41%. Found: C 52.65, H 2.77,
N 19.39%.
Compound 5e. 10-(4-Methoxy-phenyl)-10,10a-dihydro-3H-9-
oxa-1-thia-3,4-diaza-benzo[f]azulen-2-one.
Off-white
solid: mp 176-177°C; 1H NMR (400 MHz, DMSO-d6)
δ= 3.81 (3H, s), 6.75 (1H, d, J= 9.8 Hz), 6.80 (1H, d,
J =9.6 Hz), 7.08 -7.13 (4H, m), 7.54 (2H, d, J= 8.8 Hz),
7.74 (1H, s, NH), 7.85 (2H, d, J =8.8 Hz); 13C NMR
(100 MHz, DMSO-d6): δ 55.72, 55.87, 74.36, 116.27,
122.13, 127.05, 127.33, 127.70, 132.88, 136.44, 138.64,
150.86, 154.36, 157.98, 169.09; IR (cm-1): 1041-1284
(C-O), 1587 (C = N), 1647 (C = O), 3193 (Ph-OCH3),
3348 (NH); MS (ESI), m/z= 349 (M + Na+, 100%); Anal.
Calcd (C17H14N2O3S): C 62.56, H 4.32, N 8.58%. Found:
C 62.76, H 4.42, N 8.60%.
Compound 5j. 10-(2,4-Dimethoxy-phenyl)-10,10a-dihydro-
3H-9-oxa-1-thia-3,4-diaza-benzo[f]azulen-2-one.
Off-white
solid: mp 182-183°C; 1H NMR (400MHz, DMSO-d6)
δ=3.82 (6H, s), 6.36 (1H, d, J= 8.04Hz), 6.50 (1H, d,
J=8.5Hz), 7.08-7.17 (4H, m), 7.37 (1H, s), 7.53-7.55 (2H,
q, J=9.8Hz), 8.38 (1H, s, NH); 13C NMR (100MHz,
DMSO-d6): δ 49.42, 55.69, 56.24, 120.88, 122.12, 122.43,
125.09, 125.56, 126.48, 134.28, 149.10, 151.60, 153.57,
167.19; IR (cm-1): 1024-1162 (C-O), 1601 (C=N), 1633
(C=O), 2856 (Ph-OCH3), 3470 (NH); MS (ESI),
m/z=379 (M+Na+, 100%); Anal. Calcd (C18H16N2O4S):
C 60.66, H 4.53, N 7.86%. Found: C 60.68, H 4.56,
N 7.90%.
Compound 5f. 10-(4-Dimethylamino-phenyl)-10,10a-dihydro-
3H-9-oxa-1-thia-3,4-diaza-benzo[f]azulen-2-one. Off-white
solid: mp 180-181°C; 1H NMR (400 MHz, DMSO-d6)
δ= 3.04 (6H, s), 6.38 (1H, d, J= 8.9 Hz), 6.40 (1H, d,
J =7.0 Hz), 6.77 - 6.86 (4H, m), 7.40 (2H, d, J= 9.0 Hz),
7.67 (2H, d, J = 9.0 Hz), 8.50 (1H, s, NH); 13C NMR
(100 MHz, DMSO-d6): δ 44.03, 58.01, 74.89, 114.36,
119.44, 120.08, 124.48, 126.03, 127.03, 132.10, 132.90,
138.83, 153.88, 154.18, 169.03; IR (cm-1): 1064-1273
(C-S), 1353 (N-CH3), 1610 (C = N), 1646 (C = O), 3312
(NH); MS (ESI), m/z= 362 (M + Na+, 100%); Anal. Calcd
(C18H17N3O2S): C 63.70, H 5.05, N 12.38%. Found: C
63.72, H 5.15, N 12.41%.
CONCLUSIONS
In conclusion we developed an eco-friendly protocol for
the synthesis of thiazepines and oxazepines of thiazolidine
2,4dione in high yields. Ionic liquid [bmib]BF4 mediated
synthesis of desired products not only improved the yields
but also drastically reduced the reaction time. Furthermore
the eco-friendly and safety of the protocol makes it a
superior approach for the synthesis of fused heterocyclics
of thiazolidinone. This green protocol not only avoids the
use of volatile organic solvents but also offers an easy
workup to get the final products.
Compound 5 g. 10-(2-Methoxy-phenyl)-10,10a-dihydro-3H-9-
oxa-1-thia-3,4-diaza-benzo[f]azulen-2-one.
Off-white
solid: mp 191-192°C; 1H NMR (400 MHz, DMSO-d6)
δ= 3.80 (3H, s), 6.81 (1H, d, J = 7.6), 6.87 (1H, d,
J =7.7 Hz), 7.03 -7.40 (4H, m), 7.42-7.51 (4H, m), 7.97
(1H, s, NH); 13C NMR (100 MHz, DMSO-d6): δ 55.72,
55.87, 64.36, 116.27, 122.13, 127.05, 127.33, 127.70,
132.88, 136.42, 138.64, 150.86, 154.36, 157.98, 169.09;
IR (cm-1): 1120-1282 (C-S), 1601 (C = N), 1633 (C = O),
2856 (Ph-OCH3), 3470 (NH); m/z= 327 (M +1, 100%);
Anal. Calcd (C17H14N2O3S): C 62.56, H 4.32, N 8.58%.
Found: C 62.59, H 4.36, N 8.60%.
Acknowledgments. The authors are grateful to the School of
Chemistry and Physics, Discipline of Chemistry, College of
Engineering Agriculture & Science, University of KwaZulu-
Natal, Durban South Africa for funding and research facilities.
Compound 5 h. 10-(2-Nitro-phenyl)-10,10a-dihydro-3H-9-
oxa-1-thia-3,4-diaza-benzo[f]azulen-2-one.
Off-white
solid: mp 184-185°C; 1H NMR (400 MHz, DMSO-d6)
δ= 6.90 (1H, d, J= 9.2), 6.93 (1H, d, J =9.2 Hz), 7.31
(1H, s, NH), 7.69 -7.73 (4H, m), 7.81-7.85 (4H, m); 13C
NMR (100 MHz, DMSO-d6): δ 40.13, 54.24, 122.76,
123.03, 127.24, 127.85, 127.90, 128.83, 129.46,131.08,
135.35, 147.35, 149.69, 164.50, 169.88; IR (cm-1): 1028-
1271 (C-S), 1350 (Ph-NO2), 1591 (C = N), 1640 (C =O),
3403 (NH); m/z = 364 (M + Na+, 100%); Anal. Calcd
(C16H11N2O4S): C 56.30, H 3.25, N 12.31%. Found: C
56.32, H 3.28, N 12.34%.
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