Rapid synthesis of (E)-5-amino-N′-benzylidene-8-nitro-7-aryl-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbohydrazide derivatives

Article abstract of DOI:10.1080/17415993.2017.1422504

A variety of novel thiazolo/oxazolo pyridine derivatives were synthesized via an efficient, one-pot, multi-component reaction of enamines derived from the addition of cysteamine hydrochloride/ethanolamine to 1,1-bis(methylthio)-2-nitroethene with aromatic aldehydes and cyanoacetohydrazide in the presence of catalytic amount of Et₃N. This reaction includes some important aspects like simple operation under mild conditions, high atom economy, easy accessibility of reactants, simple workup procedure, and the use of EtOH/H₂O as a green reaction medium.

Full text of DOI:10.1080/17415993.2017.1422504

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: http://www.tandfonline.com/loi/gsrp20
Rapid synthesis of (E)-5-amino-N′-benzylidene-8-
nitro-7-aryl-3,7-dihydro-2H-thiazolo[3,2-
a]pyridine-6-carbohydrazide derivatives
Mohammad Bayat & Fahimeh Sadat Hosseini
To cite this article: Mohammad Bayat & Fahimeh Sadat Hosseini (2018): Rapid synthesis of
(E)-5-amino-N′-benzylidene-8-nitro-7-aryl-3,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbohydrazide
derivatives, Journal of Sulfur Chemistry, DOI: 10.1080/17415993.2017.1422504
To link to this article: https://doi.org/10.1080/17415993.2017.1422504
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Date: 11 January 2018, At: 09:52

JOURNAL OF SULFUR CHEMISTRY, 2018
https://doi.org/10.1080/17415993.2017.1422504
ꢀ
Rapid synthesis of (E)-5-amino-N -benzylidene-8-nitro-7-aryl-
,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbohydrazide
3
derivatives
Mohammad Bayat and Fahimeh Sadat Hosseini
Faculty of Science, Department of Chemistry, Imam Khomeini International University, Qazvin, Iran
ABSTRACT
ARTICLE HISTORY
A variety of novel thiazolo/oxazolo pyridine derivatives were syn-
thesized via an efficient, one-pot, multi-component reaction of
enamines derived from the addition of cysteamine hydrochlo-
ride/ethanolamine to 1,1-bis(methylthio)-2-nitroethene with aro-
matic aldehydes and cyanoacetohydrazide in the presence of cat-
alytic amount of Et3N. This reaction includes some important aspects
like simple operation under mild conditions, high atom economy,
easy accessibility of reactants, simple workup procedure, and the use
of EtOH/H2O as a green reaction medium.
Received 24 October 2017
Accepted 23 December 2017
KEYWORDS
Thiazolo/oxazolo pyridine;
multi-component reaction;
enamines; cysteamine
hydrochloride/ethanolamine;
aromatic aldehydes;
cyanoacetohydrazide
1. Introduction
Heterocyclic compounds are of very much interest in our daily life [1]. They are fre-
quently found in pharmacophores and play important roles in drug discovery and in other
fields relating to bioactive compounds [2]. Among them, compounds containing thiazole
and oxazole skeletons have been reported to furnish various biological activities [3–10].
For examples thiazolo pyridine derivatives exhibit significant pharmacological properties
including anticancer [11], antimicrobial [12], antihypertensive, muscle relaxing [13,14],
anti-inflammatory, antifungal [15], and oxazolo pyridine derivatives display antimicrobial,
anticancer, anti-inflammatory, analgesic, and anticoagulant activities [16].
During the recent years the use of enamines and dienamines derived from 1,1-
bis(methylthio)-2-nitroethene for the synthesis of various fused heterocycles and
CONTACT Mohammad Bayat
bayat_mo@yahoo.com, 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/
7415993.2017.1422504
1
©
2018 Informa UK Limited, trading as Taylor & Francis Group

2
M. BAYAT AND F. S. HOSSEINI
pharmacologically interesting heterocyclic compounds has attracted the attention of many
chemists [17–23]. To continue our studies on the synthesis of drug-like compounds
and development of 1,1-bis(methylthio)-2-nitroethene in organic synthesis, herein we
report an efficient synthesis of novel thiazolo and oxazolo pyridine derivatives via an
one-pot, multi-component reaction of enamines derived from the addition of cysteamine
hydrochloride or ethanolamine to 1,1-bis(methylthio)-2-nitroethene, with cyanoacetohy-
drazide and aromatic aldehydes.
2. Results and discussion
The reactions of cysteamine hydrochloride/ethanolamine 1, 1,1-bis(methylthio)-2-
nitroethene 2, aromatic aldehydes 3 and cyanoacetohydrazide 4 in the presence of catalytic
amount of Et N in EtOH/H O as a green medium at reflux led to the corresponding
3
2
thiazolo/oxazolo pyridine derivatives 5a–r, in good to high yields (Scheme 1).
We explored the scope of this reaction by varying the structure of the aromatic alde-
hyde component. The reaction proceeds very cleanly under the same reaction conditions
to afford a series of thiazolo/oxazolo pyridine derivatives 5 in 73–91% yields. The results
are shown in Table 1.
The structures of compounds 5a–r (Table 1) were characterized on the basis of their IR,
H NMR, C NMR and mass spectra. The H NMR spectrum of 5a showed two singlets
1
13
1
for the NH (amine) and NH (amide) groups (δ 8.01, 10.76, respectively), two singlets
2
for the methine and imine protons (δ 5.65, 8.28, respectively), and characteristic multi-
plets for the two CH groups (.3.36–3.41, 4.20–4.38) and multipets for the aromatic groups
2
1
13
(
.7.09–7.60). The H-decoupled C NMR spectrum of 5a showed 17 distinct resonances
which was consistent with the proposed structure.
The mass spectrum of 5a displayed the molecular ion peak at m/z 421, which was in
agreement with the proposed structure. The IR spectrum of 5a displayed characteristic
−
1
absorption bands (3433, 3277, 3143, 1634, 1568, 1528, 1386 and 1244 cm ) due to the
NH , NH, C9O, Ar, NO and C–N groups.
2
2
A plausible mechanism for the formation of 5 based on the chemistry of
,1-bis(methylthio)-2-nitroethene [19] is shown in Scheme 2. Initially, the reac-
1
tion between cysteamine hydrochloride/ethanolamine 1 and 1,1-bis(methylthio)-2-
nitroethene 2 affords 2-(nitromethylene)thiazolidine/oxazolidine 6 [21–23], while the
condensation of cyanoacetohydrazide 4 with aldehyde 3 furnishes adduct 7. Then, the
2-(nitromethylene)thiazolidine/oxazolidine 6 and adduct 7 undergo a Michael addition
Scheme 1. Synthetic scheme for the products 5a–r.

JOURNAL OF SULFUR CHEMISTRY
3
Table 1. Products 5a–s.
Time Yield
Entry Aminea
1
ArCHOa
Product 5
(min)
(%)
10
78
CHO
O
HCl
NH2
HS
N
NO2
N
H
H N
N
2
S
5
a
2
10
89
CHO
Cl
HCl
NH2
HS
3
10
90
HCl
NH2
HS
4
60
73
(
continued).

4
M. BAYAT AND F. S. HOSSEINI
Table 1. Continued.
Time Yield
(min) (%)
Entry Aminea
5
ArCHOa
Product 5
10
91
6
45
82
7
15
85
8
30
81
(
continued).

JOURNAL OF SULFUR CHEMISTRY
5
Table 1. Continued.
Time Yield
(min) (%)
Entry Aminea
9
ArCHOa
Product 5
40
79
10
10
83
11
10
88
12
10
82
(
continued).

6
M. BAYAT AND F. S. HOSSEINI
Table 1. Continued.
Time Yield
(min) (%)
Entry Aminea
ArCHOa
Product 5
13
15
75
14
50
80
15
15
88
16
30
82
(
continued).

JOURNAL OF SULFUR CHEMISTRY
7
Table 1. Continued.
Time Yield
(min) (%)
Entry Aminea
ArCHOa
Product 5
17
20 81
18
10
89
1
9b
10–15 78–90
aCysteamine hydrochloride/ethanolamine (1 mmol), 1,1-bis(methylthio)-2-nitroethene (1 mmol), aromatic aldehyde
2 mmol) and cyanoacetohydrazide (1 mmol) were used.
b[17].
(

8
M. BAYAT AND F. S. HOSSEINI
Scheme 2. Plausible mechanism for the formation of product 5.
to give intermediate 8, which undergoes successive imine–enamine tautomerization,
followed by nucleophilic addition of the secondary amino group to the cyano group,
leading to the formation of 5.
3. Conclusion
We have developed a facile, and efficient methodology for the Et N-catalyzed rapid prepa-
3
ration of new class of thiazolo/oxazolo pyridine derivatives via one-pot, multi-component
reaction of 2-(nitromethylene)thiazolidine/oxazolidine, aromatic aldehydes and cyanoace-
tohydrazide in ethanol/water as a green medium. The mild reaction conditions, exper-
imental simplicity, short reaction times, easy workup procedure, good to high yields and
compatibility with various functional groups make this approach attractive for synthesizing
a variety of such derivatives.
4
. Experimental
.1. General
The cysteamine hydrochloride, ethanolamine, 1,1-bis(methylthio)-2-nitroethene, cyanoace-
4
tohydrazide, aromatic aldehydes and trimethylamine (Et N) were obtained from Merck
3
and Aldrich and were used without further purification. NMR spectra were recorded
1
13
with a Bruker DRX-300 Avance instrument (300 MHz for H and 75.4 MHz for C)
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
5
975C VL MSD with Triple-Axis Detector operating at an ionization potential of 70 eV.
IR spectra were measured with a Bruker Tensor 27 spectrometer. Elemental analyses
for C, H and N were performed using a PerkinElmer 2004 series [II] CHN elemental
analyzer.

JOURNAL OF SULFUR CHEMISTRY
9
4
.2. General procedure for the synthesis of product 5
Synthesis of product 5a–m: A mixture of cysteamine hydrochloride (0.113 g, 1 mmol),
,1-bis(methylthio)-2-nitro ethylene (0.165 g, 1 mmol), 10 mL H O/EtOH (1:1) and Et N
1
2
3
(
(
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 (2 mmol), cyanoace-
tohydrazide (0.099 g, 1 mmol) and one drop Et N as a catalyst were added to the reac-
3
tion 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 H O/EtOH to give product 5a–m in excellent
2
yield.
Synthesis of product 5n–r: A mixture of ethanolamine (60 μL, 1 mmol), 1,1-
bis(methylthio)-2-nitro ethylene (0.165 g, 1 mmol) and 10 mL H O/EtOH (1:1) in a
2
5
0 mL flask was refluxed for 6 h. After completion of the reaction (monitored by TLC,
ethyl acetate/n-hexane, 1:1), aromatic aldehyde (2 mmol), cyanoacetohydrazide (0.099 g,
mmol) and one drop Et N as a catalyst were added to the reaction mixture, and it was
1
3
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
H O/EtOH to give product 5n–r in excellent yield.
2
ꢀ
4
.2.1. (E)-5-Amino-N -benzylidene-8-nitro-7-phenyl-3,7-dihydro-2H-thiazolo[3,2-a]
pyridine-6-carbohydrazide (5a)
Orange solid; yield: 0.328 g (78%); m.p. 246–248°C. H NMR (300 MHz, DMSO): δ
.36–3.41 (m, 2H, CH S), 4.20–4.38 (m, 2H, CH N), 5.65 (s, 1H, CH), 7.09–7.60 (m, 10H,
1
3
2
2
1
3
Ar), 8.01 (s, 2H, NH ), 8.28 (s, 1H, CH), 10.76 (s, 1H, NH). C NMR (75.4 MHz, DMSO): δ
2
2
1
8.1 (CH), 37.8 (CH S), 51.2 (CH N), 82.6, 124.2, 127.0, 127.8, 128.6, 129.1, 129.8, 135.3,
2 2
−
1
44.6, 145.5, 150.2, 157.2, 165.9 (C9O). IR (KBr) (v¯max/cm ): 3433 and 3277 and 3143
(
NH and NH), 1634 (C9O), 1568 (Ar), 1528 and 1386 (NO ), 1244 (C–N). MS (EI, 70 eV):
2
2
+
m/z (%) = 421 (M , 2.5), 404 (42), 274 (80), 258 (100), 227 (74), 198 (54), 171 (27), 128
(36), 90 (78), 51 (36). Anal. Calc. for C H N O S (421.47): C, 59.84; H, 4.54; N, 16.61.
21 19 5 3
Found: C, 60.2; H, 4.1, N, 16.4.
ꢀ
4
.2.2. (E)-5-Amino-N -(4-chlorobenzylidene)-7-(4-chlorophenyl)-8-nitro-3,7-dihydro-
2
H-thiazolo[3,2-a]pyridine-6-carbohydrazide (5b)
1
Orange solid; yield: 0.436 g (89%); m.p. 258–260°C. H NMR (300 MHz, DMSO):
δ 3.36–3.41 (m, 2H, CH S), 4.20–4.38 (m, 2H, CH N), 5.65 (s, 1H, CH), 7.27 (d,
2
2
3
3
3
JHH = 8.1 Hz, 2H, Ar), 7.34 (d, J
= 8.4 Hz, 2H, Ar), 7.44 (d, J
= 8.4 Hz, 2H,
HH
HH
3
Ar), 7.61 (d, J
1
1
= 8.4 Hz, 2H, Ar), 8.09 (s, 2H, NH ), 8.26 (s, 1H, CH), 10.85 (s,
HH
2
1
3
H, NH). C NMR (75.4 MHz, DMSO): δ 28.1 (CH), 37.2 (CH S), 51.2 (CH N), 81.8,
2 2
23.7, 128.5, 128.6, 129.3, 129.7, 131.6, 134.2, 143.4, 144.3, 150.3, 157.6, 165.9 (C = O).
−1
IR (KBr) (v¯ /cm ): 3471 and 3222 (NH and NH), 1633 (C = O), 1550 (Ar), 1488
max
2
+
and 1380 (NO ), 1214 (C–N). MS (EI, 70 eV): m/z (%) = 490 (M , 0.31), 430 (11),
2
3
85 (14), 292 (100), 261 (74), 222 (21), 165 (34), 124 (50), 89 (86), 63 (25). Anal.
Calc. for C H Cl N O S (490.36): C, 51.43; H, 3.49; N, 14.28. Found: C, 51.0; H, 3.1;
2
1
17
2
5
3
N, 14.6.

10
M. BAYAT AND F. S. HOSSEINI
ꢀ
4
.2.3. (E)-5-Amino-N -(3-chlorobenzylidene)-7-(3-chlorophenyl)-8-nitro–3,7-
dihydro- 2H-thiazolo[3,2-a]pyridine-6-carbohydrazide (5c)
1
Orange solid; yield: 0.441 g (90%); m.p. 255–257°C. H NMR (300 MHz, DMSO): δ
3
.37–3.42 (m, 2H, CH S), 4.22–4.40 (m, 2H, CH N), 5.69 (s, 1H, CH), 7.19–7.65 (m, 8H,
2 2
1
3
Ar), 8.12 (s, 2H, NH ), 8.25 (s, 1H, CH), 10.92 (s, 1H, NH). C NMR (75.4 MHz, DMSO):
2
δ 28.1 (CH), 37.5 (CH S), 51.3 (CH N), 81.5, 123.5, 125.9, 126.1, 126.6, 127.1, 127.6, 129.4,
2
2
1
30.6, 131.1, 133.1, 134.0, 137.5, 142.9, 147.7, 150.6, 157.7, 165.8 (C = O). IR (KBr) (v¯
max
−
1
/
cm ): 3293 and 3156 (NH and NH), 1632 (C = O), 1523 (Ar), 1473 and 1379 (NO ),
2
1
234 (C–N). Anal. Calc. for C H Cl N O S (490.36): C, 51.43; H, 3.49, N, 14.28. Found:
21 17 2 5 3
C, 51.9; H, 3.8; N, 14.6.
ꢀ
4
.2.4. (E)-5-Amino-N -(2-chlorobenzylidene)-7-(2-chlorophenyl)-8-nitro–3,7-dihydro-
2
H-thiazolo[3,2-a]pyridine-6-carbohydrazide (5d)
1
Orange solid; yield: 0.357 g (73%); m.p. 243–245°C. H NMR (300 MHz, DMSO): δ
3
8
.36–3.40 (m, 2H, CH S), 4.30–4.40 (m, 2H, CH N), 5.88 (s, 1H, CH), 7.11–7.49 (m,
2 2
1
3
H, Ar), 7.84 (s, 2H, NH ), 8.55 (s, 1H, CH), 10.94 (s, 1H, NH). C NMR (75.4 MHz,
2
DMSO): δ 28.0 (CH), 37.8 (CH S), 51.0 (CH N), 81.7, 122.9, 126.9, 127.6, 127.9, 128.8,
2
2
1
30.2, 130.3, 131.2, 131.9, 132.2, 132.4, 133.0, 140.1, 142.1, 149.9, 166.0 (C = O). Anal.
Calc. for C H Cl N O S (490.36): C, 51.43; H, 3.49; N, 14.28. Found: C, 50.9; H, 3.1; N,
2
1
17
2
5
3
1
4.5.
ꢀ
4
.2.5. (E)-5-Amino-N -(4-bromorobenzylidene)-7-(4-bromorophenyl)-8-nitro–3,7-
dihydro-2H-thiazolo[3,2-a]pyridine-6-carbohydrazide (5e)
1
Orange solid; yield: 0.526 g (91%); m.p. 271–273°C. H NMR (300 MHz, DMSO):
δ 3.35–3.41 (m, 2H, CH S), 4.22–4.40 (m, 2H, CH N), 5.64 (s, 1H, CH), 7.28 (d,
2
2
3
3
3
JHH = 8.4 Hz, 2H, Ar), 7.41 (d, J
= 8.1 Hz, 2H, Ar), 7.53 (d, J
= 8.7 Hz, 2H, Ar),
HH
HH
3
7
.58 (d, J
= 8.4 Hz, 2H, Ar), 8.08 (s, 2H, NH ), 8.24 (s, 1H, CH), 10.83 (s, 1H, NH).
HH
2
1
3
C NMR (75.4 MHz, DMSO): δ 28.1 (CH), 37.3 (CH S), 51.2 (CH N), 81.8, 120.1, 122.9,
2
2
1
23.7, 128.9, 130.1, 131.4, 132.1, 134.5, 143.5, 144.7, 150.3, 157.5, 165.7 (C = O). IR (KBr)
−
1
(
(
(
v¯
/cm ): 3472 and 3228 (NH and NH), 1632 (C = O), 1552 (Ar), 1484 and 1382
max
2
+
NO ), 1216 (C–N). MS (EI, 70 eV): m/z (%) = 579 (M , 0.40), 520 (8), 475 (10), 366
2
56), 336 (100), 307 (65), 249 (33), 209 (68), 182 (34), 155 (41), 127 (22), 89 (81), 50 (35).
Anal. Calc. for C H Br N O S (579.26): C, 43.54; H, 2.95; N, 12.09. Found: C, 43.9; H,
2
1
17
2
5
3
2
.5; N, 12.4.
ꢀ
4
.2.6. (E)-5-Amino-N -(4-methoxybenzylidene)-7-(4-methoxyphenyl)-8-nitro–3,7-
dihydro-2H-thiazolo[3,2-a]pyridine-6-carbohydrazide (5f)
1
Orange solid; yield: 0.394 g (82%); m.p. 244–246°C. H NMR (300 MHz, DMSO): δ
3
.34–3.39 (m, 2H, CH S), 3.64 (s, 3H, OCH ), 3.76 (s, 3H, OCH ), 4.15–4.32 (m, 2H,
2
3
3
3
3
CH N), 5.56 (s, 1H, CH), 6.77 (d, J
= 8.1 Hz, 2H, Ar), 6.95 (d, J
= 8.1 Hz, 2H, Ar),
2
HH
HH
3
3
7
.23 (d, J
= 8.4 Hz, 2H, Ar), 7.53 (d, J
= 8.4 Hz, 2H, Ar), 7.94 (s, 2H, NH ), 8.21
HH
HH
2
1
3
(s, 1H, CH), 10.56 (s, 1H, NH). C NMR (75.4 MHz, DMSO): δ 28.1 (CH), 36.9 (CH S),
2
5
1
3
−
1
(
EI, 70 eV): m/z (%) = 481 (M , 0.15), 422 (7), 377 (9), 335 (12), 288 (100), 257 (81), 217

JOURNAL OF SULFUR CHEMISTRY
11
(
27), 186 (13), 161 (32), 120 (19), 77 (22), 51 (10). Anal. Calc. for C H N O S (481.52):
23 23 5 5
C, 57.37; H, 4.81; N, 14.54. Found: C, 57.8; H, 4.3; N, 14.2.
ꢀ
4
.2.7. (E)-5-Amino-N -(3-methoxybenzylidene)-7-(3-methoxyphenyl)-8-nitro–3,7-
dihydro-2H-thiazolo[3,2-a]pyridine-6-carbohydrazide (5g)
1
Orange solid; yield: 0.408 g (85%); m.p. 234–236°C. H NMR (300 MHz, DMSO): δ
3
.35–3.41 (m, 2H, CH S), 3.65 (s, 3H, OCH ), 3.75 (s, 3H, OCH ), 4.19–4.39 (m, 2H,
2 3 3
CH N), 5.65 (s, 1H, CH), 6.69–7.33 (m, 8H, Ar), 8.02 (s, 2H, NH ), 8.25 (s, 1H, CH),
2
2
1
3
1
5
1
0.76 (s, 1H, NH). C NMR (75.4 MHz, DMSO): δ 28.1 (CH), 37.6 (CH S), 51.2 (CH N),
2 2
5.3 (OCH ), 55.5 (OCH ), 82.3, 110.9, 111.5, 114.4, 116.1, 119.9, 120.1, 124.0, 129.7,
3
3
30.3, 136.7, 144.4, 146.9, 150.3, 157.3, 159.3, 159.9, 165.9 (C = O). MS (EI, 70 eV): m/z
+
(
1
4
%) = 481 (M , 0.50), 422 (10), 377 (4), 335 (7), 288 (100), 257 (73), 217 (23), 186 (10),
61 (28), 134 (19), 77 (31), 51 (15). Anal. Calc. for C H N O S (481.52): C, 57.37; H,
23 23 5 5
.81; N, 14.54. Found: C, 57.1; H, 5.1; N, 14.8.
ꢀ
4
.2.8. (E)-5-Amino-N -(3,4-dimethoxybenzylidene)-7-(3,4-dimethoxyphenyl)-8-nitro–
3
,7-dihydro-2H-thiazolo[3,2-a]pyridine-6-carbohydrazide (5h)
1
Orange solid; yield: 0.430 g (81%); m.p. 240–242°C. H NMR (300 MHz, DMSO): δ
3
.34–3.39 (m, 2H, CH S), 3.65 (s, 6H, OCH ), 3.75 (s, 6H, OCH ), 4.20–4.35 (m, 2H,
2 3 3
CH N), 5.60 (s, 1H, CH), 6.63–7.20 (m, 6H, Ar), 7.97 (s, 2H, NH ), 8.20 (s, 1H, CH),
2
2
1
3
1
5
1
0.55 (s, 1H, NH). C NMR (75.4 MHz, DMSO): δ 28.1 (CH), 37.2 (CH S), 51.2 (CH N),
2 2
5.7 (OCH ), 55.9 (OCH ), 82.7, 108.1, 111.9, 112.3, 119.8, 121.7, 124.3, 128.0, 138.1,
3
3
44.8, 147.9, 148.5, 149.4, 150.0, 150.6, 156.9, 165.9 (C = O). Anal. Calc. for C H N O S
2
3
27
5
7
(541.58): C, 55.44; H, 5.03; N, 12.93. Found: C, 55.7; H, 5.5; N, 12.6.
ꢀ
4
.2.9. (E)-5-Amino-N -(4-fluorobenzylidene)-7-(4-fluorophenyl)-8-nitro–3,7-dihydro-
2
H-thiazolo[3,2-a]pyridine-6-carbohydrazide (5i)
1
Orange solid; yield: 0.361 g (79%); m.p. 246–248°C. H NMR (300 MHz, DMSO): δ
3
.36–3.41 (m, 2H, CH S), 4.22–4.39 (m, 2H, CH N), 5.65 (s, 1H, CH), 7.01–7.66
2 2
1
3
(
(
m, 8H, Ar), 8.04 (s, 2H, NH ), 8.27 (s, 1H, CH), 10.77 (s, 1H, NH). C NMR
2
2
75.4 MHz, DMSO): δ 28.1 (CH), 37.0 (CH S), 51.2 (CH N), 82.2, 115.2 (d, J = 21 Hz),
2
2
CF
2
1
16.2 (d, J = 21 Hz), 124.0, 129.0, 129.8, 131.9, 141.6, 143.6, 150.2, 157.4, 162.4 (d,
CF
1
1
−1
JCF = 243 Hz), 162.8 (d, J = 243 Hz), 165.7 (C = O). IR (KBr) (v¯
/cm ): 3470
max
CF
and 3215 (NH and NH), 1634 (C = O), 1550 (Ar), 1501 and 1383 (NO ), 1218 (C–N).
2
2
Anal. Calc. for C H F N O S (457.45): C, 55.14; H, 3.75; N, 15.31. Found: C, 55.5; H,
2
1
17
2
5
3
3
.9; N, 15.1.
ꢀ
.2.10. (E)-5-Amino-N -(3-fluorobenzylidene)-7-(3-fluorophenyl)-8-nitro–3,7-
4
dihydro-2H-thiazolo[3,2-a]pyridine-6-carbohydrazide (5j)
1
Orange solid; yield: 0.379 g (83%); m.p. 280–282°C. H NMR (300 MHz, DMSO): δ
3
8
.37–3.42 (m, 2H, CH S), 4.19–4.42 (m, 2H, CH N), 5.71 (s, 1H, CH), 6.93–7.43 (m,
2 2
1
3
H, Ar), 8.11 (s, 2H, NH ), 8.28 (s, 1H, CH), 10.90 (s, 1H, NH). C NMR (75.4 MHz,
2
2
DMSO): δ 28.1 (CH), 37.5 (CH S), 51.3 (CH N), 81.6, 112.8 (d, J = 22 Hz), 113.9 (d,
2
2
CF
2
2
2
JCF = 21 Hz), 114.6 (d, J = 21 Hz), 116.5 (d, J = 21 Hz), 123.4, 123.6, 123.9, 130.6,
CF
CF
1
1
1
31.2, 137.8, 143.2, 148.1, 150.5, 157.7, 162.4 (d, J = 243 Hz), 162.8 (d, J = 243 Hz),
CF
CF

12
M. BAYAT AND F. S. HOSSEINI
1
65.8 (C = O). Anal. Calc. for C H F N O S (457.45): C, 55.14; H, 3.75; N, 15.31.
2
1
17
2
5
3
Found: C, 55.6; H, 3.3; N, 15.6.
4.2.11. (E)-Methyl-4-(5-amino-6-(2-(4-(methoxycarbonyl)benzylidene)
hydrazincarbonyl)-8-nitro–3,7-dihydro-2H-thiazolo[3,2-a]pyridin-7-yl)benzoate (5k)
1
Orange solid; yield: 0.472 g (88%); m.p. 240–242°C. H NMR (300 MHz, DMSO): δ
3
.36–3.43 (m, 2H, CH S), 3.76 (s, 3H, OCH ), 3.83 (s, 3H, OCH ), 4.24–4.36 (m, 2H,
2
3
3
3
3
CH N), 5.76 (s, 1H, CH), 7.47 (d, J
= 8.4 Hz, 2H, Ar), 7.72 (d, J
= 8.4 Hz, 2H, Ar),
2
HH
HH
3
3
7
.82 (d, J
= 8.4 Hz, 2H, Ar), 7.95 (d, J
= 8.1 Hz, 2H, Ar), 8.13 (s, 2H, NH ), 8.33
HH
HH
2
1
3
(s, 1H, CH), 10.98 (s, 1H, NH). C NMR (75.4 MHz, DMSO): δ 28.2 (CH), 37.9 (CH S),
2
5
1
1.3 (CH N), 52.4 (OCH ), 52.6 (OCH ), 81.6, 123.5, 127.1, 127.7, 128.2, 128.4, 129.6,
2 3 3
30.0, 130.1, 139.8, 143.2, 150.6, 157.8, 165.8 (C = O), 166.3 (C = O), 166.4 (C = O).
Anal. Calc. for C H N O S (537.54): C, 55.86; H, 4.31; N, 13.03. Found: C, 55.3;
2
5
23
5
7
H, 4.0; N, 13.4.
ꢀ
4
.2.12. (E)-5-Amino-8-nitro-N -(4-nitrobenzylidene)-7-(4-nitrophenyl)-3,7-dihydro-
2
H-thiazolo[3,2-a]pyridine-6-carbohydrazide (5l)
1
Orange solid; yield: 0.419 g (82%); m.p. 235–237°C. H NMR (300 MHz, DMSO):
δ 3.39–3.45 (m, 2H, CH S), 4.22–4.43 (m, 2H, CH N), 5.83 (s, 1H, CH), 7.61 (d,
2
2
3
3
3
JHH = 8.4 Hz, 2H, Ar), 7.83 (d, J
= 8.7 Hz, 2H, Ar), 8.09 (d, J
= 8.4 Hz, 2H, Ar),
HH
HH
3
8
.36 (d, J
= 8.4 Hz, 2H, Ar), 8.38 (s, 2H, NH ), 9.44 (s, 1H, CH), 11.17 (s, 1H, NH).
HH
2
1
3
C NMR (75.4 MHz, DMSO): δ 28.2 (CH), 37.7 (CH S), 51.3 (CH N), 81.0, 123.2, 123.9,
2
2
1
24.4, 127.8, 129.1, 141.6, 142.3, 146.6, 147.7, 150.9, 152.6, 158.1, 165.7 (C = O). Anal.
Calc. for C H N O S (511.47): C, 49.31; H, 3.35; N, 19.17. Found: C, 49.6; H, 3.7; N,
2
1
17
7
7
1
9.5.
ꢀ
4
.2.13. (E)-5-Amino-8-nitro-N -(2-nitrobenzylidene)-7-(2-nitrophenyl)-3,7-dihydro-
2
H-thiazolo[3,2-a]pyridine-6-carbohydrazide (5m)
1
Orange solid; yield: 0.383 g (75%); m.p. 265–267°C. H NMR (300 MHz, DMSO): δ
3
.38–3.47 (m, 2H, CH S), 4.29–4.40 (m, 2H, CH N), 5.95 (s, 1H, CH), 7.40–8.02 (m, 8H,
2 2
Ar), 8.28 (s, 2H, NH ), 8.39 (s, 1H, CH), 10.76 (s, 1H, NH). Anal. Calc. for C H N O S
2
21 17
7
7
(511.47): C, 49.31; H, 3.35; N, 19.17. Found: C, 49.8; H, 3.5; N, 19.6.
ꢀ
4
.2.14. (E)-5-Amino-N -benzylidene-8-nitro-7-phenyl-3,7-dihydro-2H-oxazolo[3,2-
a]pyridine-6-carbohydrazide (5n)
Yellow solid; yield: 0.324 g (80%); m.p. 234–236°C. H NMR (300 MHz, DMSO): δ
.10–4.15 (m, 2H, CH N), 4.82–4.88 (m, 2H, CH O), 5.60 (s, 1H, CH), 7.07–7.60 (m, 10H,
1
4
2
2
1
3
Ar), 7.96 (s, 2H, NH ), 8.27 (s, 1H, CH), 10.69 (s, 1H, NH). C NMR (75.4 MHz, DMSO): δ
2
3
1
3
8.3 (CH), 44.1 (CH N), 71.2 (CH O), 81.7, 109.6, 126.7, 127.0, 127.9, 128.4, 129.1, 129.7,
2 2
+
35.3, 144.3, 146.2, 148.9, 157.0, 165.6 (C = O). MS (EI, 70 eV): m/z (%) = 405 (M , 2),
88 (37), 359 (12), 259 (44), 242 (75), 207 (81), 171 (99), 131 (92), 104 (52), 77 (100), 51
(73). Anal. Calc. for C H N O (405.41): C, 62.22; H, 4.72; N, 17.27. Found: C, 62.6; H,
21 19 5 4
4
.3.5; N, 17.0.

JOURNAL OF SULFUR CHEMISTRY
13
ꢀ
.2.15. (E)-5-Amino-N -(4-chlorobenzylidene)-7-(4-chlorophenyl)-8-nitro–3,7-
4
dihydro-2H-oxazolo[3,2-a]pyridine-6-carbohydrazide (5o)
1
Yellow solid; yield: 0.417 g (88%); m.p. 263–265°C. H NMR (300 MHz, DMSO): δ
4
.09–4.14 (m, 2H, CH N), 4.82–4.88 (m, 2H, CH O), 5.61 (s, 1H, CH), 7.25 (d,
2 2
3
3
3
JHH = 8.4 Hz, 2H, Ar), 7.39 (d, J
= 8.4 Hz, 2H, Ar), 7.60 (d, J
= 8.4 Hz, 2H, Ar),
HH
HH
3
13
7
.74 (d, J
= 8.4 Hz, 2H, Ar), 8.01 (s, 2H, NH ), 8.25 (s, 1H, CH), 10.77 (s, 1H, NH). C
HH
2
NMR (75.4 MHz, DMSO): δ 37.8 (CH), 44.2 (CH N), 71.3 (CH O), 81.1, 109.2, 128.3,
2
2
1
7
28.6, 129.2, 129.8, 131.3, 134.1, 134.3, 143.1, 145.1, 149.1, 157.0, 165.5 (C = O). MS (EI,
+
0 eV): m/z (%) = 474 (M , 0.08), 276 (81), 247 (55), 205 (100), 165 (34), 124 (60), 89
(96), 63 (26). Anal. Calc. for C H Cl N O (474.30): C, 53.18; H, 3.61; N, 14.77. Found:
21 17 2 5 4
C, 53.7; H, 3.3; N, 14.5.
ꢀ
4
2
.2.16. (E)-5-Amino-N -(3-fluorobenzylidene)-7-(3-fluorophenyl)-8-nitro-3,7-dihydro-
H-oxazolo[3,2-a]pyridine-6-carbohydrazide (5p)
1
Yellow solid; yield: 0.361 g (82%); m.p. 241–243°C. H NMR (300 MHz, DMSO): δ
4
.10–4.15 (m, 2H, CH N), 4.83–4.88 (m, 2H, CH O), 5.66 (s, 1H, CH), 7.15–7.42 (m, 8H,
2
2
1
3
Ar), 8.04 (s, 2H, NH ), 8.27 (s, 1H, CH), 10.83 (s, 1H, NH). C NMR (75.4 MHz, DMSO):
2
2
δ 38.1 (CH), 44.2 (CH N), 71.4 (CH O), 81.0, 109.1, 112.8 (d, J = 22 Hz), 113.6 (d,
2
2
CF
2
2
2
JCF = 21 Hz), 114.6 (d, J = 21 Hz), 116.5 (d, J = 21 Hz), 123.4, 124.0, 130.2, 131.3,
CF
CF
1
1
1
37.9, 142.9, 149.0, 149.3, 157.1, 162.8 (d, J = 243 Hz), 163.2 (d, J = 243 Hz), 165.5
CF
CF
(
C = O). MS (EI, 70 eV): m/z (%) = 260 (17), 231 (16), 189 (25), 133 (40), 107 (100), 76
(10), 57 (21). Anal. Calc. for C H F N O (441.39): C, 57.14; H, 3.88; N, 15.87. Found:
2
1
17
2
5
4
C, 57.6; H, 3.4; N, 15.5.
ꢀ
4
2
.2.17. (E)-5-Amino-8-nitro-N -(4-nitrobenzylidene)-7-(4-nitrophenyl)-3,7-dihydro-
H-thiazolo[3,2-a]pyridine-6-carbohydrazide (5q)
1
Orange solid; yield: 0.401 g (81%); m.p. 201–203°C. H NMR (300 MHz, DMSO): δ
4
.10–4.16 (m, 2H, CH N), 4.84–4.90 (m, 2H, CH O), 5.79 (s, 1H, CH), 7.66 (d,
2 2
3
3
3
JHH = 8.1 Hz, 2H, Ar), 7.83 (d, J
= 8.4 Hz, 2H, Ar), 8.07 (d, J
= 8.1 Hz, 2H,
HH
HH
3
Ar), 8.23 (d, J
= 8.4 Hz, 2H, Ar), 8.18 (s, 2H, NH ), 8.37 (s, 1H, CH), 11.10 (s, 1H,
HH
2
1
3
NH). C NMR (75.4 MHz, DMSO): δ 38.3 (CH), 44.2 (CH N), 71.6 (CH O), 80.4, 108.7,
2
2
1
23.7, 124.5, 127.8, 129.1, 141.7, 142.0, 146.5, 147.7, 149.7, 153.6, 157.3, 165.4 (C = O).
Anal. Calc. for C H N O (495.40): C, 50.91; H, 3.47; N, 19.79. Found: C, 51.3; H, 3.0;
2
1
17
7
8
N, 19.4.
4.2.18. (E)-Methyl-4-(5-amino-6-(2-(4-(methoxycarbonyl)benzylidene)
hydrazincarbonyl)-8-nitro–3,7-dihydro-2H-oxazolo[3,2-a]pyridin-7-yl)
benzoate (5r)
1
Yellow solid; yield: 0.463 g (89%); m.p. 260–262°C. H NMR (300 MHz, DMSO): δ 3.76 (s,
3
5
7
8
H, OCH ), 3.82 (s, 3H, OCH ), 4.11–4.16 (m, 2H, CH N), 4.85–4.90 (m, 2H, CH O),
3
3
2
2
3
3
.71 (s, 1H, CH), 7.52 (d, J
= 8.1 Hz, 2H, Ar), 7.71 (d, J
= 8.4 Hz, 2H, Ar),
HH
HH
3
3
.80 (d, J
= 8.1 Hz, 2H, Ar), 7.94 (d, J
= 8.1 Hz, 2H, Ar), 8.08 (s, 2H, NH ),
HH
HH
2
1
3
.32 (s, 1H, CH), 10.92 (s, 1H, NH). C NMR (75.4 MHz, DMSO): δ 38.4 (CH), 44.2
(
CH N), 52.4 (OCH ), 52.6 (OCH ), 71.4 (CH O), 80.9, 109.0, 127.1, 128.2, 128.3, 129.4,
2 3 3 2
1
30.0, 130.1, 139.8, 143.0, 149.4, 151.5, 157.2, 165.5 (C = O), 166.3 (C = O), 166.5

14
M. BAYAT AND F. S. HOSSEINI
(
C = O). Anal. Calc. for C H N O (521.48): C, 57.58; H, 4.45; N, 13.43. Found: C, 57.9;
2
5
23
5
8
H, 4.8, N, 13.1.
Disclosure statement
No potential conflict of interest was reported by the authors.
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