Synthesis, spectroscopic characterization and DFT studies on the novel indeno-thiazolopyrimidine heterocyclic system

Article abstract of DOI:10.1080/17415993.2013.801477

4-Phenyl-2-thioxo-3,4-dihydro-1H-indeno[1,2-d]pyrimidin-5(2H)-one 2, obtained by stirring a mixture of indane-1,3-dione, benzaldehyde and thiourea in acetic acid at room temperature for 12 h, on reaction with chloroacetic acid and 1,2-dibromoethane furnish compounds 3 (or 6) and 4 (or 7), respectively. The regiochemistry of the cyclized products and their structure is established by an elemental analysis, ¹H NMR, ¹³C NMR, IR and mass spectral data. Density functional theory calculations have been carried out for compounds 3 and 4 and their isomers 6 and 7 with Jaguar version 6.5112 using the B3LYP density functional method and LACVP* basis set. ¹H and ¹³C NMR of compounds 3, 4, 6 and 7 have been calculated. 2-Arylidene derivatives of 3 were obtained by two routes and their structure was established by spectral data.

Full text of DOI:10.1080/17415993.2013.801477

Journal of Sulfur Chemistry, 2014
Vol. 35, No. 1, 86–97, http://dx.doi.org/10.1080/17415993.2013.801477
Synthesis, spectroscopic characterization and DFT studies
on the novel indeno-thiazolopyrimidine heterocyclic system
Richa Gupta and Ram Pal Chaudhary*
Department of Chemistry, Sant Longowal Institute of Engineering and Technology, Longowal (Sangrur),
Punjab 148106, India
(Received 6 October 2012; final version received 28 April 2013)
4-Phenyl-2-thioxo-3,4-dihydro-1H-indeno[1,2-d]pyrimidin-5(2H)-one 2, obtained by stirring a mixture
of indane-1,3-dione, benzaldehyde and thiourea in acetic acid at room temperature for 12 h, on reaction
with chloroacetic acid and 1,2-dibromoethane furnish compounds 3 (or 6) and 4 (or 7), respectively. The
regiochemistry of the cyclized products and their structure is established by an elemental analysis, 1H
NMR, 13C NMR, IR and mass spectral data. Density functional theory calculations have been carried out
for compounds 3 and 4 and their isomers 6 and 7 with Jaguar version 6.5112 using the B3LYP density
functional method and LACVP* basis set. 1H and 13C NMR of compounds 3, 4, 6 and 7 have been
calculated. 2-Arylidene derivatives of 3 were obtained by two routes and their structure was established
by spectral data.
H
N
N
S
S
N
S
ClCH2CO2H
BrCH2CH2Br
N
NH
Ph
N
Ph
HA
HA
O
Ph
O
O
HA
O
Keywords: indane-1,3-dione; regiochemistry; spectral data; arylidene derivatives; DFT
1. Introduction
Thiazolidinone, with a carbonyl group at positions 2, 4, or 5 [1] have been subjected to an
extensive study in the recent past. Among them, 4-thiazolidinone is the most important scaffold
known to be associated with several biological activities such as antibacterial,[2] antiprotozoal,[3]
antifungal,[4] anticonvulsant,[5] anticancer,[6] antituberculosis,[7] antiparasitic,[8] anti-
inflammatory,[9] and herbicidal agents.[10] 4-Thiazolidinones have also been reported as novel
inhibitors of the bacterial enzyme Mur B, which is a precursor during the biosynthesis of
peptidologycan [11] and also non-nucleoside inhibitors of HIV RT [12] and HIV-1 integrase
inhibitors.[13]
Indenopyrimidine is an important substructure found in a number of active heterocyclic com-
pounds. The indenopyrimidines have been proved to be a novel class of non-steroidal aromatase
inhibitors, which are useful in the treatment of estrogen-dependent diseases.[14] Fused indenopy-
rimidine heterocycles have been found to exhibit solid-state fluorescent,[15] anticancer,[16] and
antiHIV [17] properties.
*Corresponding author. Email: rpchaudhary65@gmail.com
© 2013 Taylor & Francis

Journal of Sulfur Chemistry 87
In view of the wide spectrum activities of condensed 4-thiazolidinones, it was thought worth-
while to undertake the synthesis of heterocyclic systems in which 4-thiazolidinone nucleus
is fused to another biologically active heterocyclic ring. The product is expected to exhibit
more biological activity due to the synergic effect. In the present paper, 4-thiazolidinone
nucleus is fused with the indenopyrimidine system to yield two novel heterocyclic sys-
tems as 5-phenylindeno[1,2-d]thiazolo[3,2-a]pyrimidine-3,6(2H,5H)-dione 3 and 5-phenyl-2,3-
dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidin-6-(5H)-one 4. The structure and regiochemistry of
these compounds are established by spectral and computational methods.
2. Computational studies
The molecular geometry optimization and 1H and 13C NMR spectra calculations were performed
with the Jaguar software package version 6.5112 by using density functional theory (DFT) meth-
ods with B3LYP (Becke three parameter Lee-Yang-Parr) exchange correlation functional, which
combines the hybrid exchange functional of Becke,[18] with the gradient-correlation functional of
Table 1. Selected bond lengths and bond angles of the optimized compound 3.
Bond lengths (Å)
Optimized lengths
Bond angles (◦)
Sr. no.
Entry
Entry
Optimized angles
1
2
3
4
5
6
7
8
C16–H31
C16–H30
C15–O25
C15–C16
C12–S17
N11–C15
N11–C12
C10–C19
C10–H18
C10–N11
C9–N13
C8–C10
1.113
1.113
1.208
1.509
1.856
1.462
1.462
1.497
1.113
1.47
O25–C15–C16
O25–C15–N11
C16–C15–N11
C12–N13–C9
S17–C12–N13
N13–C12–N11
C15–N11–C12
C15–N11–C10
C12–N11–C10
H18–C10–N11
N13–C9–C8
122.5
122.6
118
115
126
126
124
108
108
107.5
120
120
123
123
9
10
11
12
13
14
1.456
1.497
1.337
1.208
N13–C9–C5
O14–C7–C8
O14–C7–C4
C8–C9
C7–O14
Table 2. Selected bond lengths and bond angles of the optimized compound 4.
Bond angles (◦)
Bond lengths (Å)
Sr. no.
Entry
Optimized lengths
Entry
Optimized angles
1
2
3
4
5
6
7
8
C(23)–H(37)
C(23)–H(36)
C(22)–H(35)
C(22)–H(34)
S(24)–C(12)
C(23)–S(24)
C(22)–C(23)
N(11)–C(22)
C(10)–H(15)
C(7)–O(14)
N(13)–C(9)
C(12)–N(13)
N(11)–C(12)
C(10)–N(11)
1.1130
1.1130
1.1130
1.1130
1.8560
1.7900
1.5230
1.4700
1.1130
1.2080
1.4560
1.2600
1.4620
1.4700
H(37)–C(23)–H(36)
H(36)–C(23)–C(22)
H(35)–C(22)–H(34)
C(9)–N(13)–C(12)
S(24)–C(12)–N(13)
N(13)–C(12)–N(11)
C(22)–N(11)–C(12)
C(12)–N(11)–C(10)
C(16)–C(10)–H(15)
H(15)–C(10)–N(11)
N(13)–C(9)–C(5)
N(13)–C(9)–C(8)
O(14)–C(7)–C(8)
O(14)–C(7)–C(4)
109.4
109.4
109.4
115
126
126
108
108
109.3
107.5
120
9
10
11
12
13
14
120
123
123

88 R. Gupta and R.P. Chaudhary
Lee et al. [19]. The LACVP* basis set was used for calculations in the gas phase of the structures
3 and 4 and their isomers 6 and 7, respectively. Since the crystal structure of the molecules is not
available, a DFT calculation was carried out to predict the geometry of the molecules. The opti-
mized bond lengths and bond angles obtained by geometry optimization at the B3LYP/LACVP*
level of theory of structures 3 and 4 are reported in Tables 1 and 2, respectively. In the case of
=
structure 3, the optimized bond lengths of C O and C–S in thiazolidinone ring fall in the range of
1.208Å (1.211Å) and 1.856Å (1.768Å). The optimized bond angles for O–C–N and S–C–N were
observed at 122.6◦ (124.24◦) and 126◦ (124.4◦). In the case of structure 4, the optimized bond
=
lengths of C O in indanone ring and S–C in thiazolidine ring fall in the range of 1.208Å (1.211Å)
and 1.856Å (1.768Å). The optimized bond angles for C–N–C and S–C–N were observed at 108◦
(112.6◦) and 126◦ (124.4◦). The Z-matrix (X, Y, Z coordinates of minimized structures 3, 4, 6,
and 7) are reported as supplementary information (Table S1–S4). The optimized configurations
of structures 3 and 4 and their isomers 6 and 7 with atom numbering schemes are shown in
Figure 1.
Shielding tensors of structures 3, 4, 6, and 7 were evaluated using the B3LYP functional with
the basis set given above. In order to express the chemical shifts in parts per million (ppm), the
geometry of tetramethylsilane (TMS), benzene and chloroform molecules had been optimized
and then their 1H and 13C NMR spectra were calculated by the same method using same the basis
Figure 1. Optimized geometry of compounds 3, 4 and their isomers 6, 7.

Journal of Sulfur Chemistry 89
Table 3. Experimental and calculated 1H NMR chemical shifts (ppm) of the title compound 3 and
its isomer 6.
Structure 3
Structure 6
Calc. Calc.
Expt.
NMR
Calc.
shield
Calc.
NMR
Averaged
NMR
Averaged
NMR
Entry
Entry
shield
MR
H18
H26
H27
H28
H29
H30
H31
H32
H33
H34
H35
H36
5.96
26.9551
24.9244
25.0735
24.7781
24.8015
29.2693
29.3701
24.7465
25.0724
25.0514
25.1962
25.2587
5.73
7.68
7.54
7.82
7.80
3.51
3.41
7.85
7.54
7.56
7.42
7.36
H15
H26
H27
H28
H29
H35
H36
H34
H33
H32
H31
H30
27.5011
25.3692
25.5140
25.0324
24.6011
29.4365
29.4485
25.8252
25.4375
25.4579
25.3546
24.9516
5.21
7.25
7.11
7.58
7.99
3.35
3.34
6.81
7.19
7.17
7.27
7.65
7.28
7.71
7.54
7.48
7.21
4.21
4.20
7.35
Table 4. Experimental and calculated 1H NMR chemical shifts (ppm) of the compound 4 and its
isomer 7.
Structure 4
Structure 7
Expt.
NMR
Calc.
Calc.
NMR
Averaged
NMR
Calc.
Calc.
NMR
Averaged
NMR
Entry
shield
Entry
shield
H15
H25
H26
H27
H28
H29
H30
H31
H32
H33
H34
H35
H36
H37
5.59
7.24
27.1477
25.524
25.7848
25.101
5.97
8.00
7.68
8.53
7.99
8.75
8.67
8.53
8.54
8.24
3.05
3.57
4.76
4.69
H15
H25
H26
H27
H28
H29
H30
H31
H32
H33
H36
H37
H34
H35
27.086
6.05
8.21
7.81
8.65
7.87
8.67
8.73
8.66
8.77
9.26
4.76
4.84
5.28
5.41
25.3629
25.6811
25.008
8.05
8.54
8.14
8.82
25.534
25.6281
24.9905
24.9482
25.0027
24.9154
24.5192
28.1236
28.0595
27.7064
27.6019
24.9237
24.9931
25.0989
25.0934
25.3355
29.4924
29.0762
28.1222
28.1759
7.48
3.85
3.48
3.36
4.72
5.35
set as in the case of the calculations on structures 3, 4, 6, and 7. The calculated isotropic shielding
constants σi were then transformed to chemical shifts relative to TMS by the equation
δi = σTMS − σi
Experimental and calculated 1H and 13C NMR chemical shifts (ppm) of compounds 3 and 4
and their isomers 6 and 7 have been compared in Tables 3–6. The correlation values of proton
chemical shifts are found to be 0.9990 for structure 3 and 0.9884 for its isomer 6 (Figure 2) and
0.9680 for structure 4 and 0.9464 for its isomer 7 (Figure 3). Similarly, the correlation values of
carbon chemical shifts of 3 and 6 are found to be 0.9976 and 0.8779 (Figure 4). 13C chemical shift
correlation values of 4 and its isomer 7 are found to be 0.9915 and 0.9770 (Figure 5), respectively.
The theoretical and experimental 1H and 13C data show good correlations for proposed structures
1
3 and 4. A similar correlation obtained for H and 13C data of the related compounds 8, 9, 10,
and 11 (Figure 6) validates the claim of structures 3 and 6. Moreover, the structure of 8 is proved
by the X-ray crystallography. This work is unpublished and submitted to another journal for

90 R. Gupta and R.P. Chaudhary
Table 5. Experimental and calculated 13C NMR chemical shifts (ppm) of the compound 3 and
its isomer 6.
Structure 3
Expt. NMR Calc. shield
Structure 6
Entry
Calc. NMR
Entry
Calc. shield
Calc. NMR
C1
C2
C7
C10
C12
C15
C16
138.9
132.7
167.51
55.8
160.7
170.09
32.5
70.5965
75.1962
42.2811
150.9021
54.1587
37.1898
174.5018
145.57
140.19
178.68
51.66
164.8
184.64
24.06
C1
C2
C7
C10
C12
C23
C22
63.1448
71.342
154.28
144.70
186.09
54.38
200.38
142.04
29.46
35.9439
148.5718
23.7274
73.6158
169.8781
Table 6. Experimental and calculated 13C NMR chemical shifts (ppm) of the compound 4 and
its isomer 7.
Structure 4
Calc. shield
Structure 7
Entry
Expt. NMR
Calc. NMR
Entry
Calc. shield
Calc. NMR
C1
C5
C7
C12
C22
C23
134
139
190
172
58
78.5641
72.9833
18.4964
51.4566
150.453
186.451
134.17
140.47
201.94
164.75
53.07
C1
C5
C7
C12
C24
C23
77.3528
71.5582
14.0009
57.3767
151.722
181.507
135.54
142.08
207.01
158.07
51.63
25
12.45
18.03
Structure 3
Structure 6
8
7
6
5
4
3
B3LYP/LACVP*
R2 (Structure 3) = 0.9990
R2 (Structure 6) = 0.9884
4.0
4.5
5.0
Experimental H NMR Shifts(ppm)
Figure 2. Plot of the calculated vs. the experimental 1H NMR chemical shifts (ppm).
5.5
6.0
6.5
7.0
7.5
1
publication. The correlation graphs are reported as supplementary information (Figures S1–S4).
Another similar system starting from 2-tetralone has been synthesized and the correlation of 1H
and 13C data has shown the similar results, and the work is under preparation for publication.
Dispersion corrected energies and zero point energies theoretically obtained for structures 3, 4,
6, and 7 are reported in Table 7.

Journal of Sulfur Chemistry 91
B3LYP/LACVP*
9
8
7
6
5
4
3
R2 (Structure 4) = 0.9680
R2 (Structure 7) = 0.9464
Structure 4
Structure 7
3
4
5
6
7
8
1
Experimental H NMR Shifts (ppm)
Figure 3. Plot of the calculated vs. the experimental 1H NMR chemical shifts (ppm).
220
B3LYP/LACVP*
R2 (Structure 3) = 0.9976
200
R2 (Structure 6) = 0.8779
180
160
140
120
100
80
60
Structure 3
Structure 6
40
20
20
40
60
80
100
13
120
140
160
180
Experimental C NMR Shifts (ppm)
Figure 4. Plot of the calculated vs. the experimental 13C NMR chemical shifts (ppm).
3. Results and discussion
Compound 2 was obtained by our group earlier [20] by stirring a mixture of indane-1,3-dione
1, benzaldehyde and thiourea in the acetic acid at room temperature for 12 h. IR spectrum of
1
=
=
compound 2 shows absorption bands at 1674 (C O) and 1173 (C S). In its H NMR, HA
proton appears at δ 5.36 and in mass spectrum exhibition of molecular ion peak at m/z 293
[M+ + 1] (12%) confirms its structure. This unsymmetrical thione on reaction with chloroacetic
acid followed by the cyclization of the intermediate in situ was likely to furnish compound 3
(or 6) or both (Scheme 1) depending on the mode of the cyclization. However, the thione 2
when treated with chloroacetic acid in the presence of anhyd. sodium acetate, glacial acetic acid,

92 R. Gupta and R.P. Chaudhary
200
150
100
50
B3LYP/LACVP*
R2 (Structure 4) = 0.9915
R2 (Structure 7) = 0.9770
Structure 4
Structure 7
0
20
40
60
80
100 120 140 160 180 200
13
Experimental C NMR Shifts (ppm)
Figure 5. Plot of the calculated vs. the experimental 13C NMR chemical shifts (ppm).
S
S
S
S
O
HA
O
N
N
N
N
N
N
N
N
HA
Ph
HA
Ph
HA
Ph
Ph
8
11
10
9
Figure 6. Ortep
diagram
obtained
from
X-ray
of
7-Phenyl-7,10-dihydro-5H-benzo[h]thiazolo[2,3-
b]quinazolin-9(6H)-one (8).
and acetic anhydride afforded a single product (TLC) 3 or 6 in 85% yield. The appearance of
a band at 1736 cm−1 (C O) in the IR spectrum, appearance of peaks at δ 170, 167 (C O) in
13C NMR spectrum and exhibition of a molecular ion peak at m/z 333 [M+ + 1] (100%) in the
mass spectrum of the TLC-pure product suggested that the cyclization had indeed taken place.
The IR and mass spectral data were of little help in deciding in the favor of either structure 3 or
6. However, the structure 3 was finally assigned to this cyclization product in preference to the
structure 6 on the basis of 1H NMR spectral data.
=
=
The reaction of compound 2 with 1, 2-dibromoethane gave a product which was purified by
column chromatography and characterized by its molecular ion peak at m/z 319 [M+ + 1] (100%)

Journal of Sulfur Chemistry 93
Table 7. Theoretically computed energies for structures 3, 4, 6 and 7.
Sr. no.
Parameters
Structure 3
Structure 6
Structure 4
Structure 7
1
2
Dispersion corrected energies (Kcal/mol)
Zero point energy (Kcal/mol)
−871406.74
−871397.32
−824959.19
−824956.68
168.61
181.70
195.72
195.81
O
N
S
S
N
N
N
Ph
Ph
HA
O
HA
O
6
7
H
O
N
N
S
S
PhCHO
ClCH 2CO2H
N
NH
Ph
NH2CSNH 2
Ph
O
HA
HA
O
1
O
3
O
2
RCHO
ClCH 2CO2H
RCHO
BrCH 2CH2Br
N
S
N
S
CHBR
N
N
Ph
HA
Ph
O
HA
O
O
4
(a) R= C6H5
5
(b) R= p-C6H4CH3
(c) R= p-C6H4Cl
Scheme 1. Reaction of 4-phenyl-2-thioxo-3,4-dihydro-1H-indeno[1,2-d]pyrimidin-5(2H)- one
2 with chloroacetic acid and 1,2-dibromoethane.
as a compound which could be represented by either structure 4 or 7. In either structure (4 or 7),
1
the singlet at δ 5.59 in its H NMR spectrum integrating for one proton was assignable to HA.
If the structure 6 is correct for the cyclization product, obtained from thione 2 and chloroacetic
acid, then HA will resonate in the same region as that of structure 4 (or 7). On the other hand, if
the structure 3 is correct, HA will be deshielded by the thiazolidinone ring and consequently, HA
will resonate downfield in comparison to HA in 4 (or 7). The appearance of a downfield singlet
at δ 5.96 for HA in structure 3 (or 6) as compared to singlet at δ 5.59 for HA in structure 4 (or 7)
supported the structure 3 and ruled out the structure 6 from which such a downfield shift would
=
not be expected. The deshielding effect is due to the magnetic anisotropy of the C O group with
a minor contribution from the rest of the ring.
Although the comparison of the chemical shifts of HA in the structures 3 and 4 (or 7) is on a
better footing, on the basis that both structures 3 and 4 (or 7) are tetracyclic compounds, yet the
same conclusion is derived by comparing the chemical shifts of HA of the thione 2 with that of
the cyclization product 3. The HA proton in thione 2 resonates at δ 5.36, whereas the downfield
signal at δ 5.96 (s, 1H, HA) in the cyclized product also favors the structure 3 in preference to
structure 6.

94 R. Gupta and R.P. Chaudhary
As expected in 3, HA will appear downfield in comparison to its isomer 6 due to the anisotropic
effect of carbonyl group of the thiazolidinone ring. HA (H18) of structure 3 appears at δ 5.96 (calc.
δ 5.73), while in structure 6, the chemical shift of the same proton HA (H15) is calculated at δ 5.21.
The experimental values of chemical shifts of different protons and carbons in structures 3 and 4
are in compliance with calculated values as compared to structures 6 and 7. 13C NMR spectrum
of structure 3 exhibits two peaks at δ 170 and 167 assigned to carbonyl groups of indanone
and thiazolidinone rings, respectively. These carbon chemical shifts are in good correlation with
theoretical values of 3 but not for its isomer 6.
Arylidene thiazolidinones (5) were prepared by two routes. In the first approach, thiazolidinone
3 was condensed with aldehydes to give arylidene thiazolidinones (5a–5c), while in the second
approach, compound 5a was obtained directly by heating compound 2 with chloroacetic acid and
benzaldehyde. The structures 5a–5c were established by IR and 1H NMR spectral data. The parent
thiazolidinone 3 exhibited an absorption band at 1736 cm−1 (C O), but the unsaturation at the 2-
=
position being conjugated with the carbonyl group at the 3-position as in arylidene thiazolidinones
(5a–5c) produced a bathochromic shift [21] as expected. The carbonyl absorption band appeared
at 1713, 1705, and 1713 cm−1 in structure 5a–5c, respectively.
Finally, the structure 3 is supported by a further downfield shift in the absorption spectrum of
proton HA (δ 6.21, 6.14, and 6.20, respectively) in arylidene derivatives 5a–5c as compared to 3
(δ 5.96) due to the extended conjugation of carbonyl group. This could happen only in structure
3 but not possible for structure 6. It is clear from the total energy obtained from DFT studies that
the proposed structure 3 is stable by 5.348 Kcal/mol energy from its isomer 6 (Table 7).
The structure 4 (not 7) for the product, obtained from the reaction of compound 2 with 1,
2-dibromoethane, was assigned based upon the analogy with compound 3. The structure 4 is
further supported by the fact that its carbon and proton chemical shifts are in good correlation
with DFT values rather than of structure 7. Dispersion corrected DFT calculations were carried
out for all the molecules and their dispersion corrected energies obtained supports structures 3
and 4 (Table 7).
4. Experimental
4.1. Instrumentations
Melting points were determined in sulfuric acid bath and are uncorrected. TLC was performed
on silica gel G plates using pet ether-ethylacetate (4:1) as eluent and iodine vapors as visualizing
agent. IR spectra were recorded on ABB FTIR spectrometer and the results are reported in cm−1
.
1H NMR were recorded in DMSO-d6 on a BRUKERADVANCE II 400 NMR spectrometer using
TMS as an internal standard (chemical shift in δ, ppm). The elemental analysis of compounds was
performed on a Carlo Erba-1108 elemental analyzer. The structures were optimized by molec-
ular mechanics using PM3 method based on Hyperchem with version 7.5 packages. Dispersion
corrected DFT was carried out using B97-D with Win Gamess version 2009.
4.2. Procedure for the synthesis of
4-Phenyl-2-thioxo-3,4-dihydro-1H-indeno[1,2-d]pyrimidin-5(2H)-one 2
This compound was synthesized by a conventional as well as solvent-free method using ionic
liquid by our group earlier.[20]
1
Yield 90%; mp 224–226◦C. IR spectrum, ν, cm−1: 1674 (C O), 1636 (C C), 1173 (C S). H
=
=
=
NMR spectrum (400 MHz, DMSO-d6): δ 5.36 (s, 1H, HA), 7.25–7.39 (m, 8H, C6H5), 7.86–7.91

Journal of Sulfur Chemistry 95
(m, 1H, C6H5), 9.77 (br, 1H, NH), 11.68 (br, 1H, NH). Mass spectrum, m/z (I, %): 293 [M+ + 1]
(12). C17H12N2SO. Calcd: C, 69.86; H, 4.11; N, 9.59; S, 10.96. Found: C, 69.80; H, 4.18; N, 9.51;
S, 10.89.
4.3. Procedure for synthesis of 5-Phenylindeno[1,2-d]thiazolo[3,2-a]pyrimidine-3,6
(2H,5H)-dione 3
A mixture of thione 2 (2.92 g, 0.01 mol), chloroacetic acid (0.94 g, 0.01 mol) and anhyd. sodium
acetate (0.82 g, 0.01 mol), glacial acetic acid (15 ml) and acetic anhydride (1.0 ml) was refluxed
for 5 h. The reaction mixture was kept overnight. The solid thus separated was filtered, washed
with cold ethanol, and recrystallized from ethanol to give compound 3 as orange solid.
1
Yield 85%; mp 202–204◦C. IR spectrum, ν, cm−1: 1736 (C O), 1690 (C O), 1582 (C N). H
NMR spectrum (400 MHz, DMSO-d6): δ 4.20–4.21 (m, 2H, SCH2), 5.96 (s, 1H, HA), 7.28–7.29
(m, 4H, C6H5), 7.34–7.39 (m, 5H, C6H5).13C NMR spectrum (100 MHz, DMSO-d6): δ 170, 167
=
=
=
=
=
(C O), 160 (C N), 140, 138, 133, 132, 130, 128, 127, 122, 119, 111 (Ph-C), 55, 32, 30. Mass
spectrum, m/z (I, %): 333 [M+ + 1] (100). C19H12N2O2S. Calcd: C, 68.67; H, 3.61; N, 8.43; S,
9.64. Found: C, 68.60; H, 3.69; N, 8.37; S, 9.70.
4.4. Procedure for the synthesis of
5-Phenyl-2,3-dihydroindeno[1,2-d]thiazolo[3,2-a]pyrimidin-6-(5H)-one 4
Compound 4 was obtained by stirring a mixture of thione 2 (0.292 g, 0.001 mol) and 1,2-
dibromoethane (5.0 ml) at 110◦C for 4 h. The crude solid, thus separated, was purified by column
chromatography to give compound 4 as orange solid.
Yield 75%; mp 172–174◦C. IR spectrum, ν, cm−1: 1690 (C O), 1643 (C N). H NMR spec-
trum (400 MHz, DMSO-d6): δ 3.30–3.43 (m, 2H, SCH2), 3.45–3.51 (m, 1H, NCH2), 3.83–3.86
(m, 1H, NCH2), 5.59 (s, 1H, HA), 7.24–7.48 (m, 9H, C6H5).13C NMR spectrum (100 MHz,
DMSO-d6): δ 190, 172, 164, 155, 140, 139, 138, 136, 135, 134, 131, 129, 127, 126, 121, 118,
116, 58, 51, 25. Mass spectrum, m/z (I, %): 319 [M+ + 1] (100). C19H14N2SO. Calcd: C, 71.70;
H, 4.40; N, 8.81; S, 10.06. Found: C, 71.77; H, 4.48; N, 8.89; S, 10.12.
1
=
=
4.5. Procedure for synthesis of arylidene derivatives 5a–5c:
Arylidene derivatives were prepared by two routes:
(i) A mixture of thiazolidinone 3 (0.332 g, 0.001 mol), aromatic aldehydes (0.001 mol), anhyd.
sodium acetate (0.082 g, 0.001 mol) and glacial acetic acid (10 ml) was heated under reflux for
4 h. The reaction mixture was cooled at room temperature and filtered the solid thus obtained,
crystallized from DMF-ethanol (1:1) mixture to give compounds 5a–5c.
(ii) A mixture of thione 2 (0.292 g, 0.001 mol), aromatic aldehydes (0.001 mol), chloroacetic
acid (0.094 g, 0.001 mol) and anhyd. sodium acetate (0.082 g, 0.001 mol) in glacial acetic
acid (10 ml) and acetic anhydride (1 ml) was refluxed for 4 h. A similar work up as in (i) gave
compounds 5a–5c.
4.5.1. 2-Benzylidene-5-phenylindeno[1,2-d]thiazolo[3,2-a]pyrimidine-3,6(2H,5H)-dione 5a
Brown solid, yield 70%; mp 124–126◦C. IR spectrum, ν, cm−1: 1713, 1690 (C O), 1605 (C N).
1H NMR spectrum (400 MHz, CDCl3): δ 6.21 (s, 1H, HA), 7.26–7.53 (m, 14H, ArH), 7.82
=
=

96 R. Gupta and R.P. Chaudhary
(s, 1H, HB). C26H16N2O2S. Calcd: C, 74.29; H, 3.81; N, 6.67; S, 7.62. Found: C, 74.21; H, 3.88;
N, 6.59; S, 7.69.
4.5.2. (E)-2-(4-methylbezylidene)-5-phenylindeno[1,2-d]thiazolo[3,2-a]pyrimidine-
3,6(2H,5H)-dione 5b
Brown solid, yield 68%; mp 252–254◦C. IR spectrum, ν, cm−1: 1705, 1680 (C O), 1582 (C N).
1H NMR spectrum (400 MHz, DMSO-d6): δ 2.53 (s, 3H, CH3), 6.14 (s, 1H, HA), 7.25–7.52
(m, 9H, ArH), 7.57–7.64 (m, 2H, ArH), 7.74–7.77 (m, 1H, ArH), 7.82 (s, 1H, HB), 8.01–8.04 (m,
1H, ArH). C27H18N2O2S. Calcd: C, 74.65; H, 4.15; N, 6.45; S, 7.37. Found: C, 74.58; H, 4.10;
N, 6.52; S, 7.30.
=
=
4.5.3. (E)-2-(4-chlorobenzylidene)-5-phenylindeno[1,2-d]thiazolo[3,2-a]pyrimidine-
3,6(2H,5H)-dione 5c
Brown solid, yield 72%; mp 256–258◦C. IR spectrum, ν, cm−1: 1713, 1695 (C O), 1582 (C N).
1H NMR spectrum (400 MHz, DMSO-d6): δ 6.20 (s, 1H, HA), 7.27–7.31 (m, 4H, ArH), 7.33–
8.05 (m, 9H, ArH), 7.51(s, 1H, HB). C26H15N2O2SCl. Calcd: C, 68.65; H, 3.30; N, 6.16; S, 7.04.
Found: C, 68.72; H, 3.38; N, 6.10; S, 7.10.
=
=
Acknowledgements
One of the authors RG is thankful to the authorities of Sant Longowal Institute of Engineering and Technology, ‘Longowal
for providing financial assistance. The facilities provided by SLIET authorities are gratefully acknowledged.
Supplementary online material
Supplementaryinformationontheexperimentsisavailableonthepublisherswebsiteathttp://dx.doi.org/10.1080/17415993.
2013.801477.
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