An efficient one-pot synthesis of tetrahydrothiazolo[3,2-a]quinolin-6-one derivatives

Article abstract of DOI:10.1080/17415993.2017.1391814

The cysteamine hydrochloride as a practical precursor of 2-(nitromethylene)thiazolidine in the one-pot synthesis of thiazoloquinoline derivatives from aromatic aldehydes and dimedone is described. This protocol involved Michael reaction, imine–enamine tautomerization, and cyclization sequence. Simple operation under mild conditions, easy accessibility of reactants, short reaction times, simple workup procedure, high atom economy, and the use of ethanol/water as a green medium make this approach attractive for the synthesis of variety of such derivatives.

Full text of DOI:10.1080/17415993.2017.1391814

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
An efficient one-pot synthesis of
tetrahydrothiazolo[3,2-a]quinolin-6-one
derivatives
Mohammad Bayat, Fahimeh Sadat Hosseini & Shima Nasri
To cite this article: Mohammad Bayat, Fahimeh Sadat Hosseini & Shima Nasri (2017): An
efficient one-pot synthesis of tetrahydrothiazolo[3,2-a]quinolin-6-one derivatives, Journal of Sulfur
Chemistry, DOI: 10.1080/17415993.2017.1391814
To link to this article: http://dx.doi.org/10.1080/17415993.2017.1391814
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Date: 23 October 2017, At: 09:56

JOURNAL OF SULFUR CHEMISTRY, 2017
https://doi.org/10.1080/17415993.2017.1391814
An efficient one-pot synthesis of
tetrahydrothiazolo[3,2-a]quinolin-6-one derivatives
Mohammad Bayat, Fahimeh Sadat Hosseini and Shima Nasri
Chemistry Department, Imam Khomeini International University, Qazvin, Iran
ABSTRACT
ARTICLE HISTORY
Received 3 August 2017
Accepted 10 October 2017
The cysteamine hydrochloride as a practical precursor of 2-(nitro-
methylene)thiazolidine in the one-pot synthesis of thiazoloquino-
line derivatives from aromatic aldehydes and dimedone is described.
This protocol involved Michael reaction, imine–enamine tautomer-
ization, and cyclization sequence. Simple operation under mild
conditions, easy accessibility of reactants, short reaction times,
simple workup procedure, high atom economy, and the use of
ethanol/water as a green medium make this approach attractive for
the synthesis of variety of such derivatives.
KEYWORDS
Thiazoloquinoline; 2-
(nitromethylene)thiazolidine;
aromatic aldehydes;
dimedone; one-pot reaction
O
Ar
N
NO2
S
H
O
O
S
EtOH/H2O,reflux
10-60min
ArCHO
N
H
NO2
.Potentially bioactiveproduct
. Simpleandgreenconditions
. 16examplesupto94%yield
1. Introduction
Multicomponent reactions (MCRs) are excellent strategies, employed in the synthesis of
several heterocycles and natural products [1]. They offer the advantage of simplicity and
synthetic efficiency over conventional chemical reactions as well as selectivity, convergency,
and atom economy [2].
Small-ring heterocycles including nitrogen and sulfur have been under investigation
for a long time on account of their synthetic diversity and therapeutic relevance [3–5].
For example, the thiazole ring in various natural and synthetic products has generated
interest of many groups on account of its useful biological properties [6]. Thiazole deriva-
tives exhibit promising antimicrobial, anti-inflammatory, anticonvulsant, anticancer [7],
CONTACT Mohammad Bayat
m.bayat@sci.ikiu.ac.ir
This article makes reference to supplementary material available on the publisher’s website at
https://doi.org/10.1080/17415993.2017.1391814
© 2017 Informa UK Limited, trading as Taylor & Francis Group

2
M. BAYAT ET AL.
analgesic, cardiotonic, anti-HIV, antifungal [8], antiprotozoal, antiviral [9], bactericidal
[10], and antitumor [11] activities.
The chemistry of quinoline derivatives has received particular attention over the last few
years, and a large variety of quinolines has been synthesized and assessed [12] as antibac-
terial, antimalarial, antiplasmodial, anticancer [13,14], anti-inflammatory, antiasthmatic,
antihypertensive [15,16], antitumor [17,18], antituberculosis [19,20], tuberculostatic, and
antiamoebic [21] agents. Among them, annulated thiazoloquinoline structures and those
with [3,2-a] fusion exhibit significant biological activities [22].
Heterocyclic ketene aminals (HKAs) are becoming more and more popular among
organic synthesis in the past several years [23]. The use of enamines derived from
nitro ketene dithioacetal for the synthesis of a wide variety of heterocyclic systems
and natural products has attracted the attention of many chemists [24–30]. Herein we
synthesized a new series of thiazoloquinoline derivatives via a one-pot, MCR of 2-
(nitromethylene)thiazolidine derived from the addition of cysteamine hydrochloride to
1,1-bis(methylthio)-2-nitroethene with aromatic aldehydes and dimedone.
2. Results and discussion
The one-pot multicomponent condensation reactions of cysteamine hydrochloride 1 with
l,l-bis(methylthio)-2-nitroethene 2 in the presence of Et3N with aromatic aldehydes 3 and
dimedone 4 in EtOH/H2O as a green solvent under reflux condition lead to corresponding
thiazoloquinoline derivatives 5a–5p, in excellent yields (Scheme 1).
The structures of compounds 5a–p (Table 1) were characterized on the basis of their IR,
1H NMR, 13C NMR, and mass spectra. The mass spectrum of 5a displayed the molecular
ion peak at m/z 386, which was in agreement with the proposed structure. The IR spectrum
of this compound showed absorption bands due to C O stretching (1621 cm−1) as well as
=
1
1513, 1431, and 1243 cm−1 due to the NO2 and C N groups. The H NMR spectrum of
−
5a showed two singlets for the two CH3 groups (δ 0.84, 1.02 ppm), multiplets for the two
CH2 groups (δ 2.00–2.63 ppm), multiplets for the CH2S group (δ 3.27–3.39 ppm), a singlet
for the OCH3 group (δ 3.65 ppm), multiplets for the CH2N group (δ 4.11–4.47 ppm), a
singlet for the CH group (δ 5.13 ppm), and the two doublets (δ 6.75, 7.09 ppm) for the
aromatic region (see Figure 1). The 1H-decoupled 13C NMR spectrum of 5a showed 17
distinct resonances.
Scheme 1. Synthetic scheme for the products 5a–p.

JOURNAL OF SULFUR CHEMISTRY
3
Table 1. Products 5a–p.
Entry
ArCHOa
Product
OCH3
Time (min)
15
Yield (%)
89
CHO
1
O
NO2
S
OCH3
N
5a
2
20
90
Cl
CHO
O
NO2
S
Cl
N
5b
Cl
3
10
92
CHO
Cl
O
NO2
S
N
5c
Br
4
10
94
CHO
Br
O
NO2
S
N
5d
5
30
88
CHO
O
NO2
S
N
(continued).

4
M. BAYAT ET AL.
Table 1. Continued.
Entry
6
ArCHOa
Product
Time (min)
40
Yield (%)
82
CHO
Cl
O
Cl
NO2
N
5f
S
F
7
35
78
CHO
O
NO2
S
F
N
5g
8
40
75
F
CHO
O
NO2
S
F
N
5h
OCH3
CHO
9
15
88
OCH3
O
OCH3
NO2
S
OCH3
N
5i
10
20
85
OCH3
CHO
O
NO2
S
OCH3
N
5j
(continued).

JOURNAL OF SULFUR CHEMISTRY
5
Table 1. Continued.
Entry
ArCHOa
Product
Time (min)
25
Yield (%)
88
N
CHO
11
O
NO2
S
N
N
5k
OH
12
CHO
OH
60
79
O
NO2
S
N
5l
13
40
86
Br
CHO
OH
O
OH
NO2
Br
N
S
5m
NO2
CHO
NO2
14
20
87
O
NO2
S
N
5n
15
45
78
CHO
NO2
O
NO2
NO2
N
S
5o
(continued).

6
M. BAYAT ET AL.
Table 1. Continued.
Entry
ArCHOa
Product
Time (min)
15
Yield (%)
89
O
O
CHO
16
O
NO2
S
O
O
N
5p
aCysteamine hydrochloride (1 mmol), 1,1-bis(methylthio)-2-nitroethene (1 mmol), triethylamine (1 mmol), aromatic alde-
hyde (1 mmol), and dimedone (1 mmol) in H2O/EtOH at reflux.
Figure 1. The 1H and 13C chemical shifts of 5a.
We explored the scope of this reaction by varying the structure of the aromatic alde-
hydes. The reaction proceeds very cleanly under the same reaction conditions to afford
a series of thiazoloquinoline derivatives 5 in 75–94% yields. The results are shown in
Table 1.
Based on these results, a plausible mechanism is shown in Scheme 2. Initially, the
reaction between cysteamine hydrochloride 1 and 1,1-bis(methylthio)-2-nitroethene 2
in the presence of Et3N affords 2-(nitromethylene)thiazolidine 6 [28–30]. While the
condensation of dimedone 4 with aromatic aldehyde 3 furnishes adduct 7. Then, the

JOURNAL OF SULFUR CHEMISTRY
7
Scheme 2. Plausible mechanism for the formation of product 5.
2-(nitromethylene)thiazolidine 6 and adduct 7 undergo a Michael addition to give inter-
mediate 8, which undergoes successive imine–enamine tautomerization, followed by
nucleophilic addition of the secondary amino group to the carbonyl group and then
cyclization, leading to the formation of 5.
3. Conclusion
In summary, we have described a rapid and efficient one-pot protocol for the preparation of
thiazoloquinolines in good yields through the reactions of 2-(nitromethylene)thiazolidine
with aromatic aldehydes and dimedone under mild conditions. This protocol is an exam-
ple of green chemistry since water/ethanol is used as the solvent. The other advantages
of the present procedure are simplicity of the reaction and workup, mild conditions, easy
accessibility of reactants, and high atom economy.
4. Experimental
4.1. General
The cysteamine hydrochloride, 1,1-bis(methylthio)-2-nitroethene, dimedone, aromatic
aldehydes, and triethylamine were obtained from Merck and Aldrich and were used with-
out further purification. NMR spectra were recorded with a Bruker DRX-300 Avance
1
instrument (300 MHz for H and 75.4 MHz for 13C) with DMSO as solvent. Chemical
shifts are given in ppm (δ) relative to internal TMS, and coupling constant (J) are reported
in hertz (Hz). Melting points were measured with an electrotherma1 9100 apparatus. Mass
spectra were recorded with an Agilent 5975C VL MSD with Triple-Axis Detector operat-
ing at an ionization potential of 70 eV. IR spectra were measured with Bruker Tensor 27
spectrometer.

8
M. BAYAT ET AL.
4.2. General procedure for the synthesis of product 5
A mixture of cysteamine hydrochloride (0.113 g, 1 mmol), 1,1-bis(methylthio)-2-nitro
ethylene (0.165 g, 1 mmol), 10 mL H2O/EtOH (1:1), and triethylamine (140 μL, 1 mmol)
in a 50-mL flask was refluxed for 5 h. After completion of the reaction (monitored by TLC,
ethyl acetate/n-hexane, 1:1), aromatic aldehyde (1 mmol), dimedone (0.140 g, 1 mmol)
were added to the reaction mixture, and it was stirred under reflux for the time given in
Table 1. Then, the reaction mixture was cooled to room temperature and filtered to give the
crude product. The solid was washed with water/ethanol (1:1) to give product 5 in good
yield.
4.2.1. 1,2,8,9-Tetrahydro-5-(4-methoxyphenyl)-8,8-dimethyl-4-nitro-5H-thiazolo[3,2-
a]quinolin-6(7H)-one (5a)
Yellow powder; yield: 0.343 g (86%); m.p. 304–306°C. H NMR (300 MHz, DMSO):
1
2
0.84 (s, 3H, CH3), 1.02 (s, 3H, CH3), 2.02 (d, JHH = 15.9 Hz, 1H, CH2), 2.20 (d,
2JHH = 15.9 Hz, 1H, CH2), 2.45–2.63 (m, 2H, CH2), 3.27–3.39 (m, 2H, CH2S), 3.65 (s, 3H,
OCH3), 4.11–4.21 (m, 1H, CH2N), 4.41–4.47 (m, 1H, CH2N), 5.13 (s, 1H, CH), 6.75 (d,
3JHH = 8.1 Hz, 2H, Ar), 7.09 (d, 3JHH = 8.4 Hz, 2H, Ar). 13C NMR (75.4 MHz, DMSO):
26.8, 28.6, 29.6, 32.3, 36.8, 49.7, 51.8, 55.4, 113.8, 115.8, 124.0, 129.2, 136.0, 148.9, 157.2,
158.3, 194.8. IR (KBr) (νmax/cm−1): 1621 (C O), 1513 and 1431 (NO2), 1243 (C N).
m/z (%) = 386 (M+, 49), 340 (46), 311 (27), 279 (100), 233 (21), 149 (14). Anal. Calcd. for
C20H22N2O4S (366.46): C, 62.16; H, 5.74, N, 7.25. Found: C, 62.6; H, 5.1, N, 7.1.
=
−
4.2.2. 5-(3-Chlorophenyl)-1,2,8,9-tetrahydro-8,8-dimethyl-4-nitro-5H-thiazolo[3,2-
a]quinolin-6(7H)-one (5b)
Yellow powder; yield: 0.351 g (90%); m.p. 299–301°C. 1H NMR (300 MHz, DMSO): 0.83 (s,
3H, CH3), 1.02 (s, 3H, CH3), 2.04 (d, 2JHH = 15.9 Hz, 1H, CH2), 2.20 (d, 2JHH = 15.9 Hz,
1H, CH2), 2.37–2.66 (m, 2H, CH2), 3.36–3.41 (m, 2H, CH2S), 4.12–4.21 (m, 1H, CH2N),
4.44–4.52 (m, 1H, CH2N), 5.17 (s, 1H, CH), 7.14–7.28 (m, 4H, Ar). 13C NMR (75.4 MHz,
DMSO): 26.7, 28.6, 29.5, 32.3, 37.9, 49.6, 51.9, 115.0, 123.2, 126.9, 127.1, 128.3, 130.4, 133.0,
146.1, 149.5, 157.9, 194.8. m/z (%) = 390 (M+, 10), 344 (12), 315 (6), 279 (100), 233 (13),
149 (11). Anal. Calcd. for C19H19ClN2O3S (390.88): C, 58.38; H, 4.90, N, 7.17. Found: C,
58.9; H, 5.3, N, 7.0.
4.2.3. 5-(4-Chlorophenyl)-1,2,8,9-tetrahydro-8,8-dimethyl-4-nitro-5H-thiazolo[3,2-
a]quinolin-6(7H)-one (5c)
Yellow powder; yield: 0.359 g (92%); m.p. 323–325°C. 1H NMR (300 MHz, DMSO): 0.82 (s,
3H, CH3), 1.02 (s, 3H, CH3), 2.03 (d, 2JHH = 16.2 Hz, 1H, CH2), 2.20 (d, 2JHH = 16.2 Hz,
1H, CH2), 2.38–2.64 (m, 2H, CH2), 3.26–3.40 (m, 2H, CH2S), 4.12–4.22 (m, 1H, CH2N),
3
4.41–4.49 (m, 1H, CH2N), 5.17 (s, 1H, CH), 7.21 (d, JHH = 8.4 Hz, 2H, Ar), 7.27 (d,
3JHH = 8.1 Hz, 2H, Ar). 13C NMR (75.4 MHz, DMSO): 26.8, 28.6, 29.5, 32.3, 37.5, 49.6,
51.9, 115.2, 123.4, 128.4, 130.2, 131.6, 142.8, 149.3, 157.8, 194.8. IR +(KBr) (νmax/cm−1):
=
−
1621 (C O), 1531 and 1431 (NO2), 1240 (C N). m/z (%) = 390 (M , 19), 344 (20), 315
(10), 279 (100), 233 (15), 149 (12). Anal. Calcd. for C19H19ClN2O3S (390.88): C, 58.38; H,
4.90, N, 7.17. Found: C, 58.7; H, 5.1, N, 7.1.

JOURNAL OF SULFUR CHEMISTRY
9
4.2.4. 5-(4-Bromophenyl)-1,2,8,9-tetrahydro-8,8-dimethyl-4-nitro-5H-thiazolo[3,2-
a]quinolin-6(7H)-one (5d)
Yellow powder; yield: 0.409 g (94%); m.p. 322–324°C. 1H NMR (300 MHz, DMSO): 0.82 (s,
3H, CH3), 1.02 (s, 3H, CH3), 2.03 (d, 2JHH = 16.2 Hz, 1H, CH2), 2.20 (d, 2JHH = 16.2 Hz,
1H, CH2), 2.39–2.63 (m, 2H, CH2), 3.35–3.40 (m, 2H, CH2S), 4.12–4.22 (m, 1H, CH2N),
3
4.41–4.49 (m, 1H, CH2N), 5.15 (s, 1H, CH), 7.16 (d, JHH = 7.8 Hz, 2H, Ar), 7.40 (d,
3JHH = 7.8 Hz, 2H, Ar). 13C NMR (75.4 MHz, DMSO): 26.8, 28.6, 29.5, 32.3, 37.6, 49.6,
51.9, 115.1, 120.1, 123.3, 130.6, 131.3, 143.2, 149.3, 157.8, 194.7. IR +(KBr) (νmax/cm−1):
=
1619 (C O), 1529 and 1431 (NO2), 1240 (C–N). m/z (%) = 435 (M , 21), 419 (17), 388
(18), 279 (100), 233 (23). Anal. Calcd. for C19H19BrN2O3S (435.33): C, 52.42; H, 4.40, N,
6.43. Found: C, 52.0; H, 4.6, N, 6.7.
4.2.5. 1,2,8,9-Tetrahydro-8,8-dimethyl-4-nitro-5-phenyl-5H-thiazolo[3,2-a]quinolin-
6(7H)-one (5e)
Yellow powder; yield: 0.313 g (88%); m.p. 323–325°C. 1H NMR (300 MHz, DMSO): 0.82 (s,
3H, CH3), 1.02 (s, 3H, CH3), 2.03 (d, 2JHH = 15.9 Hz, 1H, CH2), 2.20 (d, 2JHH = 15.9 Hz,
1H, CH2), 2.42–2.64 (m, 2H, CH2), 3.33–3.40 (m, 2H, CH2S), 4.12–4.22 (m, 1H, CH2N),
4.43–4.50 (m, 1H, CH2N), 5.19 (s, 1H, CH), 7.10–7.24 (m, 5H, Ar). 13C NMR (75.4 MHz,
DMSO): 26.7, 28.6, 29.6, 32.3, 37.7, 49.7, 51.9, 115.6, 123.8, 127.1, 128.2, 128.4, 143.8, 149.2,
157.6, 194.7. m/z (%) = 456 (M+, 5), 356 (19), 310 (16), 279 (100), 233 (17), 149 (12).
Anal. Calcd. for C19H20N2O3S (356.43): C, 64.02; H, 5.65, N, 7.85. Found: C, 64.5; H, 5.1,
N, 7.5.
4.2.6. 5-(2-Chlorophenyl)-1,2,8,9-tetrahydro-8,8-dimethyl-4-nitro-5H-thiazolo[3,2-
a]quinolin-6(7H)-one (5f)
Yellow powder; yield: 0.320 g (82%); m.p. 253–255°C. 1H NMR (300 MHz, DMSO): 0.83 (s,
3H, CH3), 1.02 (s, 3H, CH3), 1.97 (d, 2JHH = 16.2 Hz, 1H, CH2), 2.18 (d, 2JHH = 16.2 Hz,
1H, CH2), 2.39–2.63 (m, 2H, CH2), 3.32–3.38 (m, 2H, CH2S), 4.21–4.30 (m, 1H, CH2N),
4.39–4.47 (m, 1H, CH2N), 5.47 (s, 1H, CH), 7.10–7.35 (m, 4H, Ar). 13C NMR (75.4 MHz,
DMSO): 26.7, 28.4, 29.6, 32.1, 37.3, 49.7, 51.8, 114.7, 123.2, 127.1, 128.6, 129.8, 132.5, 133.3,
140.7, 149.4, 157.9, 194.6. IR (KBr) (νmax/cm−1): 1627 (C O), 1540 and 1447 (NO2), 1225
(C N). Anal. Calcd. for C19H19ClN2O3S (390.88): C, 58.38; H, 4.90, N, 7.17. Found: C,
58.9; H, 4.5, N, 7.4.
=
−
4.2.7. 5-(4-Fluorophenyl)-1,2,8,9-tetrahydro-8,8-dimethyl-4-nitro-5H-thiazolo[3,2-
a]quinolin-6(7H)-one (5g)
Yellow powder; yield: 0.292 g (78%); m.p. 326–328°C. 1H NMR (300 MHz, DMSO): 0.83 (s,
3H, CH3), 1.02 (s, 3H, CH3), 2.03 (d, 2JHH = 15.9 Hz, 1H, CH2), 2.20 (d, 2JHH = 16.2 Hz,
1H, CH2), 2.41–2.64 (m, 2H, CH2), 3.35–3.40 (m, 2H, CH2S), 4.12–4.22 (m, 1H, CH2N),
4.35–4.50 (m, 1H, CH2N), 5.18 (s, 1H, CH), 6.97–7.25 (m, 4H, Ar). 13C NMR (75.4 MHz,
DMSO): 26.7, 28.6, 29.6, 32.3, 37.2, 49.6, 51.9, 115.1 (d, 2JCF = 21 Hz), 123.6, 130.1, 130.2,
140.0, 149.2, 157.6, 161.1 (d, 1JCF = 243 Hz), 194.8. IR (KBr) (νmax/cm−1): 1626 (C O),
=
−
1526 and 1434 (NO2), 1199 (C N). Anal. Calcd. for C19H19FN2O3S (374.42): C, 60.94; H,
5.11, N, 7.48. Found: C, 60.6; H, 5.5, N, 7.3.

10
M. BAYAT ET AL.
4.2.8. 5-(3-Fluorophenyl)-1,2,8,9-tetrahydro-8,8-dimethyl-4-nitro-5H-thiazolo[3,2-
a]quinolin-6(7H)-one (5h)
Yellow powder; yield: 0.280 g (75%); m.p. 273–275°C. 1H NMR (300 MHz, DMSO): 0.83 (s,
3H, CH3), 1.02 (s, 3H, CH3), 2.04 (d, 2JHH = 15.9 Hz, 1H, CH2), 2.21 (d, 2JHH = 16.2 Hz,
1H, CH2), 2.39–2.65 (m, 2H, CH2), 3.36–3.41 (m, 2H, CH2S), 4.12–4.21 (m, 1H,
CH2N), 4.43–4.51 (m, 1H, CH2N), 5.21 (s, 1H, CH), 6.94–7.29 (m, 4H, Ar). 13C NMR
(75.4 MHz, DMSO): 26.7, 28.6, 29.5, 32.3, 37.8, 49.6, 51.9, 113.9 (d, 2JCF = 21 Hz), 115.0
(d, 2JCF = 21 Hz), 123.2, 124.4, 130.2, 130.3, 146.5, 149.5, 157.9, 162.4 (d, 1JCF = 243 Hz),
194.8. IR (KBr) (νmax/cm−1): 1632 (C O), 1546 and 1440 (NO2), 1223 (C N).
Anal. Calcd. for C19H19FN2O3S (374.42): C, 60.94; H, 5.11, N, 7.48. Found: C, 60.4;
H, 4.7; N, 7.0.
=
−
4.2.9. 1,2,8,9-Tetrahydro-5-(3,4-dimethoxyphenyl)-8,8-dimethyl-4-nitro-5H-
thiazolo[3,2-a]quinolin-6(7H)-one (5i)
Yellow powder; yield: 0.366 g (88%); m.p. 246–248°C. H NMR (300 MHz, DMSO):
1
2
0.86 (s, 3H, CH3), 1.03 (s, 3H, CH3), 2.05 (d, JHH = 16.2 Hz, 1H, CH2), 2.21 (d,
2JHH = 16.2 Hz, 1H, CH2), 2.37–2.66 (m, 2H, CH2), 3.30–3.39 (m, 2H, CH2S), 3.65 (s,
6H, 2OCH3), 4.11–4.21 (m, 1H, CH2N), 4.41–4.49 (m, 1H, CH2N), 5.16 (s, 1H, CH),
6.63–6.79 (m, 3H, Ar). 13C NMR (75.4 MHz, DMSO): 26.6, 28.6, 29.7, 32.3, 36.9, 49.7,
51.8, 55.9, 55.9, 111.9, 112.4, 115.6, 120.0, 123.9, 136.3, 148.0, 148.6, 149.1, 157.2, 194.9.
Anal. Calcd. for C21H24N2O5S (416.48): C, 60.56; H, 5.80, N, 6.72. Found: C, 60.1;
H, 5.3; N, 6.5.
4.2.10. 1,2,8,9-Tetrahydro-5-(3-methoxyphenyl)-8,8-dimethyl-4-nitro-5H-
thiazolo[3,2-a]quinolin-6(7H)-one (5j)
Yellow powder; yield: 0.328 g (85%); m.p. 215–217°C. 1H NMR (300 MHz, DMSO): 0.84 (s,
3H, CH3), 1.02 (s, 3H, CH3), 2.04 (d, 2JHH = 16.2 Hz, 1H, CH2), 2.21 (d, 2JHH = 16.2 Hz,
1H, CH2), 2.41–2.65 (m, 2H, CH2), 3.34–3.40 (m, 2H, CH2S), 3.66 (s, 3H, OCH3),
4.11–4.20 (m, 1H, CH2N), 4.42–4.50 (m, 1H, CH2N), 5.18 (s, 1H, CH), 6.63–6.76 (m,
3H, Ar), 7.10–7.16 (m, 1H, Ar). 13C NMR (75.4 MHz, DMSO): 26.7, 28.6, 29.6, 32.3,
37.5, 49.7, 51.9, 55.3, 111.7, 114.7, 115.4, 120.3, 123.6, 129.5, 145.2, 149.3, 157.6, 159.4,
194.8. Anal. Calcd. for C20H22N2O4S (366.46): C, 62.16; H, 5.74, N, 7.25. Found: C, 62.4;
H, 5.5; N, 7.4.
4.2.11. 5-(4-(Dimethylamino)phenyl)-1,2,8,9-tetrahydro-8,8-dimethyl-4-nitro-5H-
thiazolo[3,2-a]quinolin-6(7H)-one (5k)
Yellow powder; yield: 0.351 g (88%); m.p. 285–287°C. H NMR (300 MHz, DMSO):
1
2
0.85 (s, 3H, CH3), 1.02 (s, 3H, CH3), 2.02 (d, JHH = 15.9 Hz, 1H, CH2), 2.19 (d,
2JHH = 15.9 Hz, 1H, CH2), 2.41–2.63 (m, 2H, CH2), 2.78 (s, 6H, 2NCH3), 3.33–3.40 (m,
2H, CH2S), 4.11–4.25 (m, 1H, CH2N), 4.40–4.47 (m, 1H, CH2N), 5.08 (s, 1H, CH), 6.54 (d,
3JHH = 8.4 Hz, 2H, Ar), 6.97 (d, 3JHH = 8.4 Hz, 2H, Ar). 13C NMR (75.4 MHz, DMSO):
26.8, 28.5, 29.6, 32.3, 36.5, 49.8, 51.8, 112.4, 116.0, 124.4, 128.7, 131.8, 148.6, 149.6, 156.8,
194.8. Anal. Calcd. for C21H25N3O3S (399.50): C, 63.13; H, 6.30, N, 10.51. Found: C, 63.6;
H, 5.9; N, 10.3.

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4.2.12. 1,2,8,9-Tetrahydro-5-(4-hydroxyphenyl)-8,8-dimethyl-4-nitro-5H-
thiazolo[3,2-a]quinolin-6(7H)-one (5l)
Yellow powder; yield: 0.294 g (79%); m.p. 312–314°C. 1H NMR (300 MHz, DMSO): 0.84 (s,
3H, CH3), 1.02 (s, 3H, CH3), 2.02 (d, 2JHH = 15.9 Hz, 1H, CH2), 2.19 (d, 2JHH = 15.9 Hz,
1H, CH2), 2.36–2.62 (m, 2H, CH2), 3.23–3.38 (m, 2H, CH2S), 4.10–4.19 (m, 1H, CH2N),
3
4.40–4.48 (m, 1H, CH2N), 5.09 (s, 1H, CH), 6.57 (d, JHH = 8.1 Hz, 2H, Ar), 6.97 (d,
3JHH = 8.4 Hz, 2H, Ar), 9.22 (s, 1H, OH). 13C NMR (75.4 MHz, DMSO): 26.7, 28.5,
29.6, 32.3, 36.7, 49.7, 51.8, 115.1, 115.9, 124.2, 129.2, 134.4, 148.7, 156.4, 157.1, 194.8.
Anal. Calcd. for C19H20N2O4S (372.43): C, 61.27; H, 5.41, N, 7.52. Found: C, 60.8;
H, 5.1; N, 7.3.
4.2.13. 5-(5-Bromo-2-hydroxyphenyl)-1,2,8,9-tetrahydro-8,8-dimethyl-4-nitro-5H-
thiazolo[3,2-a]quinolin-6(7H)-one (5m)
Yellow powder; yield: 0.388 g (86%); m.p. 360–362°C. 1H NMR (300 MHz, DMSO): 0.84 (s,
3H, CH3), 1.02 (s, 3H, CH3), 1.99 (d, 2JHH = 15.9 Hz, 1H, CH2), 2.19 (d, 2JHH = 16.2 Hz,
1H, CH2), 2.35–2.58 (m, 2H, CH2), 3.20–3.40 (m, 2H, CH2S), 4.18–4.37 (m, 2H, CH2N),
5.13 (s, 1H, CH), 6.62 (d, 3JHH = 8.7 Hz, 1H, Ar), 7.09 (d, 3JHH = 8.7 Hz, 1H, Ar), 7.23 (s,
1H, Ar), 9.68 (s, 1H, OH). 13C NMR (75.4 MHz, DMSO): 26.5, 28.4, 29.6, 32.2, 36.6, 49.7,
51.7, 109.9, 113.2, 118.5, 122.0, 130.4, 130.6, 134.5, 149.6, 155.8, 158.1, 195.0. Anal. Calcd.
for C19H19BrN2O4S (451.33): C, 50.56; H, 4.24, N, 6.20. Found: C, 50.9; H, 4.6; N, 6.3.
4.2.14. 1,2,8,9-Tetrahydro-8,8-dimethyl-4-nitro-5-(4-nitrophenyl)-5h-thiazolo[3,2-
a]quinolin-6(7H)-one (5n)
Yellow powder; yield: 0.262 g (87%); m.p. 315–317°C. 1H NMR (300 MHz, DMSO): 0.82 (s,
3H, CH3), 1.02 (s, 3H, CH3), 2.03 (d, 2JHH = 15.9 Hz, 1H, CH2), 2.21 (d, 2JHH = 16.2 Hz,
1H, CH2), 2.42–2.66 (m, 2H, CH2), 3.37–3.43 (m, 2H, CH2S), 4.16–4.25 (m, 1H, CH2N),
3
4.43–4.51 (m, 1H, CH2N), 5.30 (s, 1H, CH), 7.50 (d, JHH = 8.7 Hz, 2H, Ar), 8.08 (d,
3JHH = 8.7 Hz, 2H, Ar). 13C NMR (75.4 MHz, DMSO): 26.8, 28.7, 29.5, 32.3, 38.4, 49.5,
51.9, 114.6, 122.9, 123.6, 129.7, 146.6, 149.8, 151.1, 158.3, 194.7. IR (KBr) (νmax/cm−1):
=
−
1634 (C O), 1517 and 1438 (NO2), 1215 (C N). Anal. Calcd. for C19H19N3O5S (401.43):
C, 56.84; H, 4.77, N, 10.46. Found: C, 56.5; H, 4.9; N, 10.3.
4.2.15. 1,2,8,9-Tetrahydro-8,8-dimethyl-4-nitro-5-(2-nitrophenyl)-5h-thiazolo[3,2-
a]quinolin-6(7H)-one (5o)
Yellow powder; yield: 0.235 g (78%); m.p. 276–278°C. 1H NMR (300 MHz, DMSO): 0.78 (s,
3H, CH3), 1.00 (s, 3H, CH3), 1.95 (d, 2JHH = 15.9 Hz, 1H, CH2), 2.16 (d, 2JHH = 15.9 Hz,
1H, CH2), 2.41–2.62 (m, 2H, CH2), 3.32–3.40 (m, 2H, CH2S), 4.17–4.26 (m, 1H, CH2N),
4.41–4.49 (m, 1H, CH2N), 6.01 (s, 1H, CH), 7.33–7.80 (m, 4H, Ar). 13C NMR (75.4 MHz,
DMSO): 26.9, 28.5, 29.3, 32.2, 33.8, 49.6, 52.0, 115.3, 123.3, 124.5, 128.3, 130.7, 133.5, 138.2,
148.9, 149.5, 158.5, 194.8. Anal. Calcd. for C19H19N3O5S (401.43): C, 56.84; H, 4.77, N,
10.46. Found: C,56.4; H, 5.0; N, 10.1.
4.2.16. Methyl-4-(2,5,6,7,8,9-hexahydro-8,8-dimethyl-4-nitro-6-oxo-1H-thiazolo[3,2-
a]quinolin-5-yl)benzoate (5p)
Yellow powder; yield: 0.368 g (89%); m.p. >380°C. 1H NMR (300 MHz, DMSO): 0.80 (s,
3H, CH3), 1.02 (s, 3H, CH3), 2.02 (d, 2JHH = 15.9 Hz, 1H, CH2), 2.20 (d, 2JHH = 16.2 Hz,

12
M. BAYAT ET AL.
1H, CH2), 2.39–2.65 (m, 2H, CH2), 3.34–3.40 (m, 2H, CH2S), 3.78 (s, 3H, OCH3),
4.11–4.23 (m, 1H, CH2N), 4.43–4.49 (m, 1H, CH2N), 5.25 (s, 1H, CH), 7.35 (d,
3JHH = 8.1 Hz, 2H, Ar), 7.81 (d, 3JHH = 8.1 Hz, 2H, Ar). 13C NMR (75.4 MHz, DMSO):
26.6, 28.6, 29.6, 32.3, 38.2, 49.6, 51.9, 52.5, 115.0, 123.2, 128.4, 128.7, 129.4, 149.0, 149.5,
158.0, 166.4, 194.7. Anal. Calcd. for C21H22N2O5S (414.47): C, 60.85; H, 5.35, N, 6.75.
Found: C, 61.2; H, 5.0; N, 6.5.
Disclosure statement
No potential conflict of interest was reported by the authors.
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