Synthesis of highly functionalized hydropyridones: thiazolo[3,2-a]pyridin-5-one-6-carbohydrazones and tetrahydroimidazo[1,2-a]pyridin-5-one-2-carbohydrazones

Article abstract of DOI:10.1080/17415993.2020.1770252

Synthesis of functionalized 2-pyridone derivatives from thiazolo[3,2-a]pyridine-6-carbohydrazides or tetrahydroimidazo[1,2-a]pyridine-6-carbohydrazides was developed using acetic acid as solvent at 70°C. Various carbohydrazides could be applied to this protocol, and the desired 2-pyridone products were isolated in excellent yields by simple filtration. This method has several additional advantages, such as simple operation, mild reaction conditions, simple work up, easy product isolation, and preparation of potentially bioactive compounds.

Full text of DOI:10.1080/17415993.2020.1770252

Journal of Sulfur Chemistry
ISSN: 1741-5993 (Print) 1741-6000 (Online) Journal homepage: https://www.tandfonline.com/loi/gsrp20
Synthesis of highly functionalized hydropyridones:
thiazolo[3,2-a]pyridin-5-one-6-carbohydrazones
and tetrahydroimidazo[1,2-a]pyridin-5-one-2-
carbohydrazones
Masoud Mohamadi Vala, Mohammad Bayat & Yadollah Bayat
To cite this article: Masoud Mohamadi Vala, Mohammad Bayat & Yadollah Bayat (2020):
Synthesis of highly functionalized hydropyridones: thiazolo[3,2-a]pyridin-5-one-6-carbohydrazones
and tetrahydroimidazo[1,2-a]pyridin-5-one-2-carbohydrazones, Journal of Sulfur Chemistry, DOI:
10.1080/17415993.2020.1770252
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JOURNAL OF SULFUR CHEMISTRY
https://doi.org/10.1080/17415993.2020.1770252
Synthesis of highly functionalized hydropyridones:
thiazolo[3,2-a]pyridin-5-one-6-carbohydrazones and
tetrahydroimidazo[1,2-a]pyridin-5-one-2-carbohydrazones
a
a
and Yadollah Bayatb
Masoud Mohamadi Vala , Mohammad Bayat
a
Department of Chemistry, Faculty of Science, Imam Khomeini International University, Qazvin, Iran;
Department of Chemistry and Chemical Engineering, Malek Ashtar University of Technology, Tehran, Iran
b
ABSTRACT
ARTICLE HISTORY
Received 8 April 2020
Accepted 12 May 2020
Synthesis of functionalized 2-pyridone derivatives from thiazolo
[3,2-a]pyridine-6-carbohydrazides or tetrahydroimidazo[1,2-a]
pyridine-6-carbohydrazides was developed using acetic acid as sol-
vent at 70°C. Various carbohydrazides could be applied to this pro-
tocol, and the desired 2-pyridone products were isolated in excel-
lent yields by simple filtration. This method has several additional
advantages, such as simple operation, mild reaction conditions, sim-
ple work up, easy product isolation, and preparation of potentially
bioactive compounds.
KEYWORDS
Thiazolopyridine;
Imidazopyridine; acetic acid;
2-pyridone; hydrolysis
1. Introduction
Bicyclic pyridone scaffolds are present in a lot of biologically active heterocyclic com-
pounds and exhibit diverse and important medical and biological properties [1,2]. Among
them, compounds containing thiazine, thiazole and imidazole skeletons are very active in
terms of biologic properties [3,4], and show anticancer [5], antimicrobial [6], insecticidal
[
[
7] antibacterial [8], antifungal [9], antihypertensive, anxioselective [10], hypnoselective
11], anti-HIV [12], antivarial and antiallergic [13,14] properties.
During the past decades, specific strategies have been reported for the synthesis
of pyridone and its derivatives [15–20]. For examples in 2013 Fukuyama et al. pre-
pared 2-pyridone derivatives by means of an efficient protocol including the 1,4-addition
of 2-(phenylsulfinyl)acetamide to α,β-unsaturated ketones followed by cyclization and
CONTACT Mohammad Bayat
m.bayat@sci.ikiu.ac.ir
Supplemental data for this article can be accessed here. https://doi.org/10.1080/17415993.2020.1770252
2020 Informa UK Limited, trading as Taylor & Francis Group
©

2
M. M. VALA ET AL.
sulfoxide elimination (Scheme 1, entry a) [21]. In 2017 Goryaeva et al. reported syn-
thesis of 1-(2-aminoethyl)-6-alkyl-4-polyfluoroalkylpyridin-2-ones based on the acidic
cleavage of 7-hydroxy-7-polyfluoroalkylhexahydroimidazo[1,2-a]pyridin-5-ones. In this
method the pyridones can be obtained as bases, salts, acetamides, or the products of
intramolecular cyclization, dihydroimidazopyridines, depending on the reaction con-
ditions (Scheme 1, entry b) [22]. Also in 2018 we developed a simple and conve-
nient protocol for the synthesis of N-amino-3-cyano-2-pyridone derivatives by a one-
pot reaction of cyanoacetohydrazide, aromatic aldehydes and activated nitrile sub-
strates (malononitrile, ethylcyanoacetate, cyanoacetamide) in the presence of piperi-
dine in water or a mixture of water and ethanol at room temperature (Scheme 1,
entry c) [23]. In this paper, we describe synthesis of new functionalized 2-pyridone
ꢀ
derivatives by acid hydrolysis of (E)-5-amino-N -benzylidene-8-nitro-7-aryl-2,3-dihydro-
7
7
ꢀ
H-thiazolo[3,2-a]pyridine-6-carbohydrazide and (E)-5-amino-N -benzylidene-8-nitro-
-aryl-1,2,3,7-tetrahydroimidazo[1,2-a]pyridine-6-carbohydrazide derivatives as precur-
sors in a mixture of acetic acid and water (7:3) as solvent at 70°C (Scheme 1, entry
d).
Preliminary bioassays showed that some of the tetrahydroimidazo[1,2-a]pyridine-5-
one compounds containing an electronegative pharmacophore ( =NNO or =CNO )
2
2
exhibited good insecticidal activity. The insecticidal activities varied significantly depend-
ing on the types and patterns of the substituents, which provided guidance for further
investigation on structure modification [1,24]. Thus, a great deal of effort has been
made to develop new methods for the synthesis of tetrahydroimidazo[1,2-a]pyridine-5-
one compounds. Our method to prepare target compounds 6a-o start with the synthe-
sis of thiazolo[3,2-a]pyridine-6-carbohydrazide or tetrahydroimidazo[1,2-a]pyridine-6-
carbohydrazide derivatives 5a-o as precursors, which synthesized via an efficient, one-pot,
multi-component reaction of enamines (derived from the addition of ethylenediamine or
cysteamine hydrochloride to 1,1-bis(methylthio)-2-nitroethene) with aromatic aldehydes
and cyanoacetohydrazide in the presence of catalytic amount of triethylamine in ethanol
at reflux (Scheme 2) [25,26].
2. Results and discussion
ꢀ
The hydrolysis of (E)-5-amino-N -benzylidene-8-nitro-7-aryl-2,3-dihydro-7H-thiazolo
[
ꢀ
3,2-a]pyridine-6-carbohydrazide and (E)-5-amino-N -benzylidene-8-nitro-7-aryl-1,2,3,
7
-tetrahydroimidazo[1,2-a]pyridine-6-carbohydrazide derivatives 5a-o in AcOH/H O
2
(7:3) as solvent at 70°C led to the corresponding pyridone derivatives 6a-o in good to high
yields (Scheme 3).
In order to optimize the reaction conditions, thiazolo[3,2-a]pyridine-6-carbohydrazide
compound 5a was used as the model substrate and several reagents were examined to set
up a standard reaction conditions. The results are summarized in Table 1. Experimental
results showed that the reaction proceeded very cleanly with 80% yield within 6 h, when
the acetic acid 70% was used as solvent at 70°C (Table 1, entry 1). The product was formed
in 70% yield within 14 h, when the acetic acid 70% was used at 40°C (Table 1, entry 2). The
reaction did not work. When the acetic acid 70% was used at 100°C, the desired product
was not observed (Table 1, entry 3). The reaction proceeded with 75% yield within 6 h,

JOURNAL OF SULFUR CHEMISTRY
3
Scheme 1. Methods for the construction of some pyridone derivatives.
Scheme 2. Synthesis of thiazolo[3,2-a]pyridine-6-carbohydrazid and tetrahydroimidazo[1,2-
a]pyridine-6-carbohydrazide derivatives.

4
M. M. VALA ET AL.
Scheme 3. Synthetic scheme for the products 6a-o.
Table 1. Synthetic results of 6a under different solvent conditions
a
Entry
Reagent
Time (h)
T (°C)
Yield (%)
1
2
3
4
5
6
7
8
9
AcOH 70%
AcOH 70%
AcOH 70%
HCl 2.5%
p-TSA 15%
p-TSA 30%
Lactic Acid 20%
HCO2H 30%
NaOH 2%
6
14
2
6
1
70
40
100
70
70
70
70
70
70
80
70
Dec.
75
75
72
Mix
15 min
Overnight
5
61
Overnight
No reaction
aReaction conditions: thiazolo[3,2-a]pyridine-6-carbohydrazide 5a (0.5 mmol), AcOH 70% (10 ml). dec.: decomposition, n.r.:
no reaction.
when the hydrochloric acid 2.5% was used as solvent at 70°C (Table 1, entry 4). Using p-
TSA 15% and 30% as catalyst for about 1 h, and 15 min, resulted in the target compound
6a wit 90 75% and 72% yields, respectively (Table 1, entries 5 and 6). The reaction did not
proceed to completion in lactic acid (LA) 20% and sodium hydroxide 2%, so a lot of spots
were observed on TLC (Table 1, entries 7 and 9). Also, with formic acid 3%, the product
was formed in 61% yield within 5 h (Table 1, entry 8).
We explored the scope of this reaction by varying the structure of the aromatic alde-
hyde components used in synthesis of the thiazolo[3,2-a] pyridine-6-carbohydrazide or
tetrahydroimidazo[1,2-a]pyridine-6-carbohydrazide derivatives 5a-o. The reaction pro-
ceeds cleanly under the same reaction conditions (acetic acid 70%, 70°C) to afford pyridone
derivatives 6a-o in 62-98% yields (Table 2).
The reaction did not work, when the carbohydrazide derivatives 5 having electron-
donating groups (such as OH or OMe) at the ortho position of aromatic ring, were used.
Also, efficiency of the reaction increased, when compounds with the NO or Cl substituent
2
were used.
1
13
The structures of compounds 6a-o were deduced from their IR, H NMR, C NMR and
mass spectra (see the supporting information). The product 6a possess two chiral centers
and therefore two diastereoisomers are expected (Scheme 4).

JOURNAL OF SULFUR CHEMISTRY
5
Table 2. Products 6a-o.
Ratio
Entry
Major product
minor Product
Time (h) Yield (%)
(M:m)a
1
12
80
62:38
2
6
95
53:47
3
4
5
0.5
86
76
98
63:37
6
64:36
2
67:33
(
continued).

6
M. M. VALA ET AL.
Table 2. Continued.
Ratio
Entry
Major product
minor Product
Time (h) Yield (%)
(M:m)a
6
12
91
56:44
7
12
86
60:40
8
0.2
93
70:30
9
5
79
64:36
10
4
73
63:37
(
continued).

JOURNAL OF SULFUR CHEMISTRY
7
Table 2. Continued.
Ratio
Entry
Major product
minor Product
Time (h) Yield (%)
(M:m)a
11
2
86
60:40
12
4
81
68:32
13
2.5
62
74:26
14
2
95
53:47
15
12
71
65:35
aM: major diastereomer, m: minor diastereomer.

8
M. M. VALA ET AL.
Scheme 4. The two diastereoisomers of 6a.
The H and 13C-NMR spectrums of the crude product showed the resonances of the
1
two diastereoisomers. We were not able to separate 6a in pure form. However, its NMR
1
13
data can be extracted from the mixture of the two isomers. As representative, H and
C
NMR of thiazolo[3,2-a]pyridine-6-carbohydrazide 6a are shown in Scheme 4.
1
The H NMR spectrum of 6a showed one singlet for the NH group (δ 12.08 ppm), one
singlet for imine group (δ 8.08 ppm), multiplets for aromatic groups (δ 7.11-7.77 ppm),
one singlet for the CHCO group (δ 4.94 ppm), multiplets for the CH N group (δ 4.39-
2
4
.43 ppm), one singlet for the CH-Ar group (δ 3.85 ppm), multiplets for the CH S group
2
(δ 3.44-3.51 ppm), for the major diastereoisomer (62%); and also one singlet for the NH
group (δ 12.12 ppm), one singlet for imine group (δ 8.21 ppm), multiplets for aromatic
groups (δ 7.11-7.77 ppm), one singlet for the CHCO group (δ 4.76 ppm), one singlet for the
CH-Ar group (δ 4.67 ppm), multiplets for the CH N group (δ 4.10-4.26 ppm), multiplets
2
for the CH S group (δ 3.44-3.51 ppm), for the minor diastereoisomer (38%) (Schemes 4
2
and 5).
The H-decoupled 13C NMR spectrum of 6a showed 21 distinct signals in agree-
ment with the proposed structure. For the major diastereoisomer, resonances due to
CH S, CHCO, CH-Ar, CH N, C-NO , NCS, CH of imine, and two C = O groups
1
2
2
2
appeared at δ = 29.3, 42.4, 49.9, 49.9, 123.0, 142.1, 147.3, 163.8 and 168.7 ppm, respec-
tively; and for the minor diastereoisomer, resonances due to CH S, CHCO, CH-Ar,
2
CH N, C-NO , NCS, CH of imine, and two C = O groups appeared at δ = 29.3,
2
2
4
2.2, 50.0, 53.1, 123.0, 142.8, 147.3, 160.4 and 163.3 ppm, respectively (Schemes 5
and 6).
The mass spectrum of 6a displayed the molecular ion peak at m/z 491, which was in
agreement with the proposed structure. The IR spectrum of 6a displayed characteristic
absorption bands due to the NH, C = O, Ar, NO , and C–N groups at 3454, 1664, 1589,
2
−
1
1
465, 1364, and 1281 cm , respectively.
ꢀ
A proposed mechanism for the formation of (E)-N -(arylidene)-7-(aryl)-8-nitro-5-oxo-
,3,6,7-tetrahydro-5H-thiazolo[3,2-a]pyridine-6-carbohydrazide 6 is shown in Scheme 7.
2
First, the reaction between diamine 1 and nitroethene 2 affords ketene aminal A, While
the condensation of aldehyde 3 with 4 furnishes adduct B. Then, the α-C of ketene aminal
A attacks the C = C bond of the B to generate the intermediate D via a Michael reac-
tion. The intermediate D form the intermediate E via imine-enamine tautomerization.
Next, the amino group attacks to the cyano group, leading to the formation of 5. Second,

JOURNAL OF SULFUR CHEMISTRY
9
Scheme 5. H and 13C NMR spectrums of two diastereoisomers of 6a.
1
+
addition of H O to compound 5 in the presence of H furnishes intermediate G, and
2
+
proton transfer between H O and NH affords intermediate H which undergoes elim-
2
2
ination of NH , followed by successive enol-keto tautomerization led to the formation of
3
product 6.

10
M. M. VALA ET AL.
Scheme 6. H and 13C NMR chemical shifts of 6a.
1
Scheme 7. Proposed mechanism for the formation of product 6.
3. Conclusion
In summary, we have developed an efficient approach to the synthesis of new function-
alized 2-pyridone derivatives by conversion of thiazolo[3,2-a]pyridine-6-carbohydrazide
and tetrahydroimidazo[1,2-a]pyridine-6-carbohydrazide derivatives in AcOH/H O (7:3)
2

JOURNAL OF SULFUR CHEMISTRY
11
as solvent at 70°C. The mild reaction conditions, experimental simplicity, easy work-up
procedure, compatibility with various functional groups, and good to high yields make
this approach attractive for the synthesis a variety of such derivatives.
4. Experimental
4.1. General
The cysteamine hydrochloride, 1,1-bis(methylthio)-2-nitroethene, cyanoacetohydrazide,
aromatic aldehydes, triethylamine and acetic acid, were obtained from Merck and Aldrich
and were used without further purification. NMR spectra were recorded with a Bruker
1
13
19
DRX-300 Avance instrument (300 MHz for H, 75.4 MHz for C, and 470 MHz for F)
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 operating at an ionization potential of 70 eV. IR spectra
were measured with, Bruker Tensor 27 spectrometer.
4
.2. General procedure for the synthesis of product 6
Synthesis of 5a: A mixture of cysteamine hydrochloride (0.113 g, 1 mmol), 1,1-
bis(methylthio)-2-nitro ethylene (0.165 g, 1 mmol), 10 mL H O/EtOH (1:1), and Et N
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 reaction
3
mixture, and it was stirred under reflux for 10 min. 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 in 89% yield [21].
2
A mixture of tetrahydroimidazo[1,2-a]pyridine-6-carbohydrazide 5a (0.5 mmol) and
1
0 mL AcOH/H O (7:3) were stirred in a 50 mL flask at a temperature 70°C in the duration
2
of the time given in Table 1. Then, the mixture of the reaction was cooled to room temper-
ature and filtered to give the crude product. The solid was washed with H O to produce
2
6
a-o. After the completion of the reaction, it was monitored by TLC, ethyl acetate/n-hexane
(
1:1).
ꢀ
.2.1. (E)-N -(3-chlorobenzylidene)-7-(3-chlorophenyl)-8-nitro-5-oxo-2,3,6,7-
4
tetrahydro-5H-thiazolo[3,2-a]pyridine-6-carbohydrazide (6a)
Yellow solid: mp = 259–261°C, 0.189 g, yield 77%; IR (KBr) (ν¯max/cm−1): 3454 (NH),
1
664 (C = O), 1589 (Ar), 1465 and 1364 (NO ), 1281 (C–N). MS (EI, 70 eV): m/z
2
+
(
1
5
%) = 491 (0.05) [M] , 318 (43), 293 (59), 276 (40), 262 (34), 225 (42), 165 (100), 154 (87),
27 (58), 111 (58), 89 (37), 75 (41), 60 (40). Anal. Calcd for C H Cl N O S (491.34): C,
21 16 2 4 4
1.34; H, 3.28; N, 11.40. Found: C, 51.6; H, 3.7; N, 11.0.
1
Major diastereomer (62%), H NMR (300 MHz, DMSO-d ): δ 3.44–3.51 (m, 2 H,
6
CH S), 4.39–4.43 (m, 2 H, CH N), 4.67 (s, 1 H, CH Ar-H), 4.76 (s, 1 H, CHCO), 7.11–7.77
2
2
1
3
(
m, 8 H, Ar-H), 8.08 (s, 1 H, CH = N), 12.08 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
d ): δ 29.3 (CH S), 42.4 (CH), 49.9 (CHCO), 53.1 (CH N), 123.0, 123.9, 125.1, 126.4,
6
2
2

12
M. M. VALA ET AL.
127.2, 127.7, 128.5, 130.4, 131.2, 131.6, 134.2, 136.3, 142.1, 144.6, 147.3, 163.8 and 168.7 (2
C = O).
1
Minor diastereomer (38%), H NMR (300 MHz, DMSO-d ): δ 3.44–3.51 (m, 2 H,
6
CH S), 3.85 (s, 1 H, CH Ar-H), 4.10–4.26 (m, 2 H, CH N), 4.94 (s, 1 H, CHCO), 7.11–7.77
2
2
1
3
(
m, 8 H, Ar-H), 8.21 (s, 1 H, CH = N), 12.12 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
d ): δ 29.3 (CH S), 42.3 (CH), 50.2 (CHCO), 53.1 (CH N), 123.0, 123.9, 125.1, 126.2,
6
2
2
1
27.1, 127.7, 128.3, 130.4, 131.2, 131.5, 134.1, 136.5, 142.9, 144.6, 147.3, 160.4 and 163.3 (2
C = O).
ꢀ
.2.2. (E)-N -(2-chlorobenzylidene)-7-(2-chlorophenyl)-8-nitro-5-oxo-2,3,6,7-
4
tetrahydro-5H-thiazolo[3,2-a]pyridine-6-carbohydrazide (6b)
Bright yellow solid; mp = 204–206°C, 0.233 g, yield 95%; IR (KBr) (ν¯max/cm−1): 3443
(
NH), 1692 (C = O), 1584 (Ar), 1453 and 1374 (NO ), 1286 (C–N). Anal. Calcd for
2
C H Cl N O S (491.34): C, 51.34; H, 3.28; N, 11.40. Found: C, 51.5; H, 3.7; N, 11.1.
2
1
16
2
4
4
1
Major diastereomer (53%), H NMR (300 MHz, DMSO-d ): δ 3.29–3.41 (m, 2 H,
6
CH S), 4.42–4.46 (m, 2 H, CH N), 4.68 (s, 1 H, CH Ar-H), 5.10 (s, 1 H, CHCO), 7.10–7.91
2
2
1
3
(
m, 8 H, Ar-H), 8.43 (s, 1 H, CH = N), 12.08 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
d ): δ 29.1 (CH S), 50.1 (CH), 50.9 (CHCO), 54.0 (CH N), 123.7, 127.9, 128.4, 128.6,
6
2
2
1
30.1, 130.2, 130.3, 130.4, 131.3, 132.1, 132.7, 133.6, 137.2, 141.6, 145.3, 168.3 and 172.5 (2
C = O).
Minor diastereomer (47%), H NMR (300 MHz, DMSO-d ): δ 3.29–3.41 (m, 2 H,
1
6
CH S), 3.65 (s, 1 H, CH Ar-H), 4.13–4.23 (m, 2 H, CH N), 5.17 (s, 1 H, CHCO), 7.10–7.91
2
2
1
3
(
m, 8 H, Ar-H), 8.62 (s, 1 H, CH = N), 12.13 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
d ): δ 29.1 (CH S), 50.1 (CH), 50.9 (CHCO), 54.0 (CH N), 123.7, 127.3, 128.4, 128.7,
6
2
2
1
30.2, 130.3, 130.4, 130.7, 131.3, 132.6, 132.7, 133.9, 136.6, 141.6, 145.3, 160.1 and 162.9 (2
C = O).
ꢀ
.2.3. (E)-N -(4-fluorobenzylidene)-7-(4-fluorophenyl)-8-nitro-5-oxo-2,3,6,7-
4
tetrahydro-5H-thiazolo[3,2-a]pyridine-6-carbohydrazide (6c)
Yellow solid: mp = 274–276°C, 0.197 g, yield 86%; IR (KBr) (ν¯max/cm−1): 3448
(
NH), 1666 (C = O), 1593 (Ar), 1508 and 1367 (NO ), 1283 (C–N). Anal. Calcd for
2
C H F N O S (458.44): C, 55.02; H, 3.52; N, 12.22. Found: C, 55.4; H, 3.2; N, 12.4.
2
1
16
2
4
4
1
Major diastereomer (63%), H NMR (300 MHz, DMSO-d ): δ 3.18–3.46 (m, 2 H,
6
CH S), 4.40–4.44 (m, 2 H, CH N), 4.56 (s, 1 H, CH Ar-H), 4.76 (s, 1 H, CHCO), 7.13–7.77
2
2
1
3
(
m, 8 H, Ar-H), 8.09 (s, 1 H, CH = N), 11.89 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
2
d ): δ 29.3 (CH S), 42.0 (CH), 49.8 (CHCO), 53.4 (CH N), 116.4 (d, J = 21 Hz), 116.6
6
2
2
CF
2
1
(
1
-
d, J = 21 Hz), 123.7, 124.6, 128.8, 129.7, 129.8, 135.8, 145.0, 161.6 (d, J = 230 Hz),
CF
CF
1
19
61.9 (d, J = 230 Hz), 163.9 and 168.5 (2 C = O). F NMR (470 MHz, DMSO-d ): δ
CF
6
109.98 (Ar-F).
1
Minor diastereomer (37%), H NMR (300 MHz, DMSO-d ): δ 3.18–3.46 (m, 2 H,
6
CH S), 3.80 (s, 1 H, CH Ar-H), 4.12–4.21 (m, 2 H, CH N), 4.90 (s, 1 H, CHCO), 7.13–7.77
2
2
1
3
(
m, 8 H, Ar-H), 8.22 (s, 1 H, CH = N), 11.92 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
2
d ): δ 29.2 (CH S), 41.9 (CH), 49.9 (CHCO), 53.4 (CH N), 116.3 (d, J = 21 Hz),
6
2
2
CF
2
1
1
16.5 (d, J = 21 Hz), 123.7, 124.6, 129.1, 129.8, 129.9, 135.7, 147.8, 160.4 (C = O),
CF
1 1 19
61.6 (d, J = 230 Hz), 161.9 (d, J = 230 Hz), 163.1 (C = O). F NMR (470 MHz,
CF
CF
DMSO-d ): δ -114.56 (Ar-F).
6

JOURNAL OF SULFUR CHEMISTRY
13
ꢀ
.2.4. (E)-N -(3-fluorobenzylidene)-7-(3-fluorophenyl)-8-nitro-5-oxo-2,3,6,7-
4
tetrahydro-5H-thiazolo[3,2-a]pyridine-6-carbohydrazide (6d)
Yellow solid: mp = 264–266°C, 0.174 g, yield 76%; IR (KBr) (ν¯max/cm−1): 3421 (NH),
1
665 (C = O), 1590 (Ar), 1460 and 1365 (NO ), 1273 (C–N). MS (EI, 70 eV): m/z
2
+
(
(
(
%) = 458.44 (0) [M] , 441 (32), 319 (25), 308 (100), 290 (25), 277 (44), 247 (30), 225
37), 151 (42), 138 (82), 111 (35), 95 (48), 75 (21), 60 (31). Anal. Calcd for C H F N O S
2
1
16
2
4
4
458.44): C, 55.02; H, 3.52; N, 12.22.
1
Major diastereomer (64%), H NMR (300 MHz, DMSO-d ): δ 3.34–3.47 (m, 2 H,
6
CH S), 4.40–4.42 (m, 2 H, CH N), 4.67 (s, 1 H, CH Ar-H), 4.76 (s, 1 H, CHCO), 6.99–7.55
2
2
1
3
(
m, 8 H, Ar-H), 8.09 (s, 1 H, CH = N), 12.00 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
2
d ): δ 29.2 (CH S), 42.4 (CH), 49.8 (CHCO), 53.1 (CH N), 113.4 (d, J = 22 Hz), 114.4
6
2
2
2
CF
2
2
(
d, J = 22 Hz), 115.3 (d, J = 22 Hz), 117.6 (d, J = 22 Hz), 122.6, 123.2, 124.3,
CF
CF
CF
1
1
31.3, 131.6, 136.7, 136.8, 142.5, 144.7, 161.2 (C = O), 161.5 (d, J = 264 Hz), 162.9 (d,
CF
1
19
J
= 264 Hz), 168.7 (C = O). F NMR (470 MHz, DMSO-d ): δ -112.07 (Ar-F).
CF
6
1
Minor diastereomer (36%), H NMR (300 MHz, DMSO-d ): δ 3.34–3.47 (m, 2 H,
6
CH S), 3.84 (s, 1 H, CH Ar-H), 4.17–4.20 (m, 2 H, CH2N), 4.94 (s, 1 H, CHCO), 6.99–7.55
2
1
3
(
m, 8 H, Ar-H), 8.23 (s, 1 H, CH = N), 12.00 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
2
d ): δ 24.9 (CH S), 42.2 (CH), 49.8 (CHCO), 53.1 (CH N), 113.7 (d, J = 22 Hz), 114.4
6
2
2
2
CF
2
2
(
d, J = 22 Hz), 115.3 (d, J = 22 Hz), 117.6 (d, J = 22 Hz), 122.8, 123.2, 124.3,
CF
CF
CF
1
1
31.4, 136.6, 136.7, 136.8, 142.6, 147.6, 161.2 (C = O), 161.5 (d, J = 264 Hz), 162.9 (d,
CF
1
19
J
= 264 Hz), 164.5 (C = O). F NMR (470 MHz, DMSO-d ): δ -112.78 (Ar-F).
CF
6
ꢀ
4
.2.5. (E)-N -(3-methoxybenzylidene)-7-(3-methoxyphenyl)-8-nitro-5-oxo-2,3,6,7-
tetrahydro-5H-thiazolo[3,2-a]pyridine-6-carbohydrazide (6e)
Yellow solid: mp = 206–208°C, 0.236 g, yield 98%; IR (KBr) (ν¯max/cm−1): 3421
(
NH), 1704 (C = O), 1588 (Ar), 1462 and 1364 (NO ), 1287 (C–N). Anal. Calcd for
2
C H N O S (482.51): C, 57.25; H, 4.60; N; 11.61. Found: Found: C, 56.8; H, 4.2; N; 11.3.
2
3
22
4
6
1
Major diastereomer (67%), H NMR (300 MHz, DMSO-d ): δ 3.20–3.43 (m, 2 H,
6
CH S), 3.73 (s, 3 H, OCH ), 3.76 (s, 3 H, OCH ), 4.32–4.49 (m, 2 H, CH N), 4.61 (s, 1 H,
2
3
3
2
CH Ar-H), 4.77 (s, 1 H, CHCO), 6.69–7.42 (m, 8 H, Ar-H), 8.20 (s, 1 H, CH = N), 11.89 (s,
1
3
1
H, NH). C NMR (75.4 MHz, DMSO-d ): δ 29.3 (CH S), 42.4 (CH), 49.7 (CHCO), 53.4
6 2
(
1
CH N), 55.4 (OCH ), 55.5 (OCH ), 111.6, 113.1, 113.5, 117.1, 118.3, 120.6, 123.5, 130.4,
30.9, 135.5, 140.9, 146.2, 148.8, 160.0 (C- OCH ), 160.2 (C- OCH ), 164.3 and 168.6 (2
3 3
2 3 3
C = O).
1
Minor diastereomer (33%), H NMR (300 MHz, DMSO-d ): δ 3.20–3.43 (m, 2 H,
6
CH S), 3.73 (s, 3 H, OCH ), 3.76 (s, 3 H, OCH ), 3.83 (s, 1 H, CH Ar-H), 4.05–4.20 (m, 2
2
3
3
H, CH N), 4.86 (s, 1 H, CHCO), 6.69–7.42 (m, 8 H, Ar-H), 8.67 (s, 1 H, CH = N), 11.91
2
1
3
(
s, 1 H, NH). C NMR (75.4 MHz, DMSO-d ): δ 29.2 (CH S), 42.4 (CH), 49.8 (CHCO),
3.4 (CH N), 55.4 (OCH ), 55.5 (OCH ), 111.7, 113.1, 113.2, 117.1, 118.5, 120.6, 123.5,
2 3 3
6 2
5
1
1
30.4, 130.9, 135.5, 140.9, 146.2, 148.8, 160.0 (C-OCH ), 160.1 (C = O), 160.2 (C-OCH ),
3
3
63.2 (C = O).
ꢀ
4
5
.2.6. (E)-8-nitro-N -(4-nitrobenzylidene)-7-(4-nitrophenyl)-5-oxo-2,3,6,7-tetrahydro-
H-thiazolo[3,2-a]pyridine-6-carbohydrazide (6f)
Bright orange solid: mp = 211–213°C, 0.233 g, yield 91%; IR (KBr) (ν¯max/cm−1): 3450
(
NH), 1704 (C = O), 1593 (Ar), 1459 and 1344 (NO ), 1279 (C–N). MS (EI, 70 eV): m/z
2

14
M. M. VALA ET AL.
+
(
%) = 512 (0) [M] , 298 (54), 514 (25), 176 (100), 165 (36), 130 (40), 103 (31), 76 (33).
Anal. Calcd for C H N O S (512.45): C, 49.22; H, 3.15; N, 16.40.
2
1
16
6
8
1
Major diastereomer (56%), H NMR (300 MHz, DMSO-d ): δ 3.22–3.46 (m, 2 H,
6
CH S), 4.40–4.45 (m, 2 H, CH N), 4.75 (s, 1 H, CH Ar-H), 4.93 (s, 1 H, CHCO), 7.47–8.34
2
2
1
3
(
m, 8 H, Ar-H), 8.30 (s, 1 H, CH = N), 12.17 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
d ): δ 29.3 (CH S), 42.5 (CH), 49.9 (CHCO), 52.5 (CH N), 123.0, 124.6, 124.9, 128.5, 128.7,
6
2
2
1
40.2, 143.9, 146.7, 146.9, 147.5, 148.4, 168.6 and 172.5 (2 C = O).
1
Minor diastereomer (44%), H NMR (300 MHz, DMSO-d ): δ 3.22–3.46 (m, 2 H,
6
CH S), 3.90 (s, 1 H, CH Ar-H), 4.19–4.23 (m, 2 H, CH N), 5.11 (s, 1 H, CHCO), 7.47–8.34
2
2
1
3
(
m, 8 H, Ar-H), 7.95 (s, 1 H, CH = N), 12.20 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
d ): δ 29.3 (CH S), 42.2 (CH), 49.9 (CHCO), 52.5 (CH N), 123.7, 124.4, 124.7, 128.4, 128.6,
6
2
2
1
40.4, 143.9, 146.7, 146.9, 147.1, 148.5, 160.5 and 163.3 (2 C = O).
ꢀ
4
.2.7. (E)-N -(4-bromobenzylidene)-7-(4-bromophenyl)-8-nitro-5-oxo-2,3,6,7-
tetrahydro-5H-thiazolo[3,2-a]pyridine-6-carbohydrazide (6g)
Yellow solid: mp = 274–276°C, 0.250 g, yield 86%; IR (KBr) (ν¯max/cm−1): 3438 (NH),
1
665 (C = O), 1590 (Ar), 1464 and 1366 (NO ), 1283 (C–N). MS (EI, 70 eV): m/z
2
+
(
%) = 580 (0.08) [M] , 225 (36), 197 (100), 170 (21), 155 (26), 118 (32), 92(73), 74 (51),
6
5 (54). Anal. Calcd for C H Br N O S (580.25): C, 43.47; H, 2.78; N, 9.66.
21 16 2 4 4
1
Major diastereomer (60%), H NMR (300 MHz, DMSO-d ): δ 3.28–3.48 (m, 2 H,
6
CH S), 4.40–4.46 (m, 2 H, CH N), 4.58 (s, 1 H, CH Ar-H), 4.75 (s, 1 H, CHCO), 7.13–7.71
2
2
1
3
(
m, 8 H, Ar-H), 8.07 (s, 1 H, CH = N), 11.93 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
d ): δ 29.3 (CH S), 42.1 (CH), 49.8 (CHCO), 53.2 (CH N), 121.5, 123.3, 124.2, 129.1, 129.4,
6
2
2
1
29.5 132.4, 133.3, 139.0, 145.1, 147.8, 163.8 and 168.5 (2 C = O).
1
Minor diastereomer (40%), H NMR (300 MHz, DMSO-d ): δ 3.28–3.48 (m, 2 H,
6
CH S), 3.81 (s, 1 H, CH Ar-H), 4.10–4.18 (m, 2 H, CH N), 4.89 (s, 1 H, CHCO), 7.13–7.71
2
2
1
3
(
m, 8 H, Ar-H), 8.20 (s, 1 H, CH = N), 11.97 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
d ): δ 29.2 (CH S), 42.0 (CH), 49.9 (CHCO), 53.2 (CH N), 121.4, 123.3, 124.2, 129.1, 129.4,
6
2
2
1
29.5 132.3, 133.5, 138.9, 145.1, 147.8, 160.2 and 163.3 (2 C = O).
ꢀ
4
.2.8. (E)-N -(2,6-dichlorobenzylidene)-7-(2,5-dichlorophenyl)-8-nitro-5-oxo-2,3,6,7-
tetrahydro-5H-thiazolo[3,2-a]pyridine-6-carbohydrazide (6h)
Bright yellow solid: mp = 227–229°C, 0.260, yield 93%; IR (KBr) (ν¯max/cm−1): 3453
(
NH), 1702 (C = O), 1566 (Ar), 1499 and 1367 (NO ), 1240 (C–N). Anal. Calcd for
2
C H Cl N O S (560.23): C, 45.02; H, 2.52; N, 10.00.
2
1
16
2
4
4
1
Major diastereomer (70%), H NMR (300 MHz, DMSO-d ): δ 3.27–3.40 (m, 2 H,
6
CH S), 4.59 (s, 1 H, CH Ar-H), 5.36–5.47 (m, 2 H, CH N), 5.58 (s, 1 H, CHCO), 7.05–7.68
2
2
1
3
(
m, 6 H, Ar-H), 8.29 (s, 1 H, CH = N), 12.43 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
d ): δ 24.9 (CH S), 28.5 (CH), 50.2 (CHCO), 50.3 (CH N), 114.2, 116.3, 122.0, 129.2, 129.6,
6
2
2
1
30.1, 133.3, 134.4, 140.0, 141.5, 146.5, 165.6 and 169.9 (2 C = O).
1
Minor diastereomer (30%), H NMR (300 MHz, DMSO-d ): δ 3.27–3.40 (m, 2 H,
6
CH S), 4.21–4.57 (m, 2 H, CH N), 4.59 (s, 1 H, CH Ar-H), 5.61 (s, 1 H, CHCO), 7.05–7.68
2
2
1
3
(
m, 6 H, Ar-H), 8.19 (s, 1 H, CH = N), 12.20 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
d ): δ 24.9 (CH S), 28.5 (CH), 50.2 (CHCO), 50.3 (CH N), 114.2, 116.1, 122.0, 129.1, 129.8,
6
2
2
1
30.1, 131.6, 134.2, 140.2, 141.5, 149.3, 159.4 and 162.8 (2 C = O).

JOURNAL OF SULFUR CHEMISTRY
15
ꢀ
.2.9. (E)-N -(4-chlorobenzylidene)-7-(4-chlorophenyl)-8-nitro-5-oxo-2,3,6,7-
4
tetrahydro-5H-thiazolo[3,2-a]pyridine-6-carbohydrazide (6i)
Yellow solid: mp = 280–282°C, 0.194 g, yield 79%; IR (KBr) (ν¯max/cm−1): 3453
(
NH), 1702 (C = O), 1595 (Ar), 1488 and 1375 (NO ), 1291 (C–N). Anal. Calcd for
2
C H Cl N O S (491.34): C, 51.34; H, 3.28; N, 11.40.
2
1
16
2
4
4
1
Major diastereomer (64%), H NMR (300 MHz, DMSO-d ): δ 3.14–3.54 (m, 2 H,
6
CH S), 4.39–4.43 (m, 2 H, CH N), 4.58 (s, 1 H, CH Ar-H), 4.76 (s, 1 H, CHCO), 7.19–7.71
2
2
1
3
(
m, 8 H, Ar-H), 8.08 (s, 1 H, CH = N), 11.93 (s, 1 H, NH). CNMR (75.4 MHz, DMSO-
d ): δ 29.3 (CH S), 42.1 (CH), 49.8 (CHCO), 53.2 (CH N), 123.4, 128.7, 129.2, 129.3, 129.4,
6
2
2
1
29.5, 133.0, 133.1, 135.3, 138.6, 145.0, 163.8 and 168.5 (2 C = O).
1
Minor diastereomer (36%), H NMR (300 MHz, DMSO-d ): δ 3.14–3.54 (m, 2 H,
6
CH S), 3.81 (s, 1 H, CH Ar-H), 4.16–4.20 (m, 2 H, CH N), 4.91 (s, 1 H, CHCO), 7.19–7.71
2
2
1
3
(
m, 8 H, Ar-H), 8.21 (s, 1 H, CH = N), 11.98 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
d ): δ 29.2 (CH S), 42.0 (CH), 49.9 (CHCO), 53.2 (CH N), 123.4, 128.7, 129.1, 129.3, 129.4,
6
2
2
1
29.7, 133.0, 133.1, 135.3, 138.4, 145.0, 163.1 and 163.3 (2 C = O).
ꢀ
4
.2.10. (E)-N -benzylidene-8-nitro-5-oxo-7-phenyl-2,3,6,7-tetrahydro-5H-
thiazolo[3,2-a]pyridine-6-carbohydrazide (6j)
Yellow solid: mp = 252–254°C, 0.154 g, yield 73%; IR (KBr) (ν¯max/cm−1): 3421 (NH),
1
664 (C = O), 1591 (Ar), 1461 and 1365 (NO ), 1282 (C–N). MS (EI, 70 eV): m/z
2
+
(
%) = 422.46 (0.1) [M] , 405 (35), 285 (100), 259 (77), 229 (41), 207 (49), 180 (27), 132
(
90), 120 (92), 104 (39), 89 (32), 77 (88), 60 (37). Anal. Calcd for C H N O S (422.10):
21 18 4 4
C, 59.71; H, 4.29; N, 13.26.
1
Major diastereomer (63%), H NMR (300 MHz, DMSO-d ): δ 3.25–3.47 (m, 2 H,
6
CH S), 4.42–4.47 (m, 2 H, CH N), 4.56 (s, 1 H, CH Ar-H), 4.77 (s, 1 H, CHCO), 7.18–7.69
2
2
1
3
(
m, 10 H, Ar-H), 8.11 (s, 1 H, CH = N), 11.90 (s, 1 H, NH). CNMR (75.4 MHz, DMSO-
d ): δ 29.3 (CH S), 42.6 (CH), 49.7 (CHCO), 53.6 (CH N), 123.7, 124.7, 126.7, 127.0, 127.6,
6
2
2
1
28.4, 129.4, 129.7, 134.1, 139.6, 146.2, 164.1 and 168.6 (2 C = O).
1
Minor diastereomer (37%), H NMR (300 MHz, DMSO-d ): δ 3.25–3.47 (m, 2 H,
6
CH S), 3.81 (s, 1 H, CH Ar-H), 4.42–4.45 (m, 2 H, CH N), 4.88 (s, 1 H, CHCO), 7.18–7.69
2
2
1
3
(
m, 10 H, Ar-H), 8.23 (s, 1 H, CH = N), 11.92 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-
d ): δ 29.2 (CH S), 42.6 (CH), 49.8 (CHCO), 53.6 (CH N), 123.7, 124.7, 126.7, 127.0, 127.7,
6
2
2
1
28.3, 129.3, 129.6, 134.2, 139.5, 146.2, 160.0 and 163.2 (2 C = O).
ꢀ
4
2
.2.11. (E)-N -(3,4-dimethoxybenzylidene)-7-(3,4-dimethoxyphenyl)-8-nitro-5-oxo-
,3,6,7-tetrahydro-5H-thiazolo[3,2-a]pyridine-6-carbohydrazide (6k)
Yellow solid: mp = 209–211°C, 0.233, yield 86%; IR (KBr) (ν¯max/cm−1): 3406 (NH), 1668
(
(
C = O), 1588 (Ar), 1515 and 1364 (NO ), 1273 (C–N). Anal. Calcd for C H N O S
2
25 26
4
8
542.56): C, 55.34; H, 4.83; N, 10.33.
1
Major diastereomer (60%), H NMR (300 MHz, DMSO-d ): δ 3.29–3.45 (m, 2 H,
6
CH S), 3.56–3.70 (m, 6 H, OCH ), 4.45–4.47 (m, 2 H, CH N), 4.62 (s, 1 H, CH Ar-H),
2
3
2
4
.75 (s, 1 H, CHCO), 6.56–7.27 (m, 6 H, Ar-H), 8.02 (s, 1 H, CH = N), 11.76 (s, 1 H, NH).
1
Minor diastereomer (40%), H NMR (300 MHz, DMSO-d ): δ 3.29–3.45 (m, 2 H,
6
CH S), 3.56–3.70 (m, 6 H, OCH ), 3.74 (s, 1 H, CH Ar-H), 4.08–4.14 (m, 2 H, CH N),
2
3
2
4
.82 (s, 1 H, CHCO), 6.56–7.27 (m, 6 H, Ar-H), 8.16 (s, 1 H, CH = N), 11.76 (s, 1 H, NH).

16
M. M. VALA ET AL.
ꢀ
4
.2.12. (E)-N -(3-fluorobenzylidene)-7-(3-fluorophenyl)-8-nitro-5-oxo-1,2,3,5,6,7-
hexahydro-imidazo[1,2-a]pyridine-6-carbohydrazide (6l)
White solid: mp = 242–244°C, yield 81%; IR (KBr) (ν¯max/cm−1): 3531 (NH), 3456 (NH),
1
680 (C = O), 1589 (Ar), 1486 and 1386 (NO ), 1191 (C–N), 1148 (C–N). Anal. Calcd for
2
C H F N O (441.39): C, 57.14; H, 3.88; N, 15.87.
2
1
17
2
5
4
1
Major diastereomer (68%), H NMR (300 MHz, DMSO-d ): δ 3.82–3.91 (m, 2 H,
6
CH NH), 3.97–4.06 (m, 2 H, CH N), 4.53 (s, 1 H, CH Ar-H), 4.64 (s, 1 H, CHCO),
2
2
1
3
7
.01–7.54 (m, 6 H, Ar-H), 8.11 (s, 1 H, CH = N), 9.91 (s, 1 H, NH), 11.98 (s, 1 H, NH). C
NMR (75.4 MHz, DMSO-d ): δ 42.0 (CH NH), 43.3 (CH), 44.2 (CHCO), 53.6 (CH N),
6
2
2
2
2
2
1
1
(
04.5 (C-NO ), 113.3 (d, J = 23 Hz), 114.0 (d, J = 21 Hz), 114.8 (d, J = 21 Hz),
2
CF
CF
CF
2
17.6 (d, J = 21 Hz), 117.7, 122.8, 123.0, 124.0, 124.2, 131.4, 136.7, 144.6, 152.8, 162.8
CF
1
1
d, J = 249 Hz), 162.9 (d, J = 244 Hz), 165.0, 169.5 (C = O).
CF
CF
1
Minor diastereomer (32%), H NMR (300 MHz, DMSO-d ): δ 3.74 (s, 1 H, CH Ar-H),
6
δ 3.82–3.91 (m, 2 H, CH NH), 3.97–4.06 (m, 2 H, CH N), 4.76 (s, 1 H, CHCO), 7.01–7.54
2
2
1
3
(
(
m, 6 H, Ar-H), 8.11 (s, 1 H, CH = N), 9.91 (s, 1 H, NH), 12.01 (s, 1 H, NH). C NMR
75.4 MHz, DMSO-d ): δ 42.3 (CH NH), 43.3 (CH), 44.2 (CHCO), 55.5 (CH N), 105.2 (C-
6
2
2
2
2
2
NO ), 113.3 (d, J = 23 Hz), 114.0 (d, J = 21 Hz), 114.8 (d, J = 21 Hz), 117.6 (d,
2
CF
CF
CF
2
J
= 21 Hz), 122.8, 123.0, 124.0, 124.2, 131.3, 136.6, 144.4, 152.6, 161.2 (C = O), 162.8
CF
1
1
(
d, J = 249 Hz), 162.9 (d, J = 244 Hz), 165.0 (C = O).
CF
CF
ꢀ
.2.13. (E)-N -(4-fluorobenzylidene)-7-(4-fluorophenyl)-8-nitro-5-oxo-1,2,3,5,6,7-
4
hexahydro-imidazo[1,2-a]pyridine-6-carbohydrazide (6m)
White solid: mp = 266–268°C, 0.137 g, yield 62%; IR (KBr) (ν¯max/cm−1): 3288 (NH), 3181
(
NH), 1719 and 1647 (C = O), 1647, 1496 and 1383 (NO ), 1218 (C–N), 1162 (C–N).
2
Anal. Calcd for C H F N O (441.39): C, 57.14; H, 3.88; N, 15.87.
2
1
17
2
5
4
1
Major diastereomer (74%), H NMR (300 MHz, DMSO-d ): δ 3.70–3.88 (m, 2 H,
6
CH NH), 3.96–4.02 (m, 2 H, CH N), 4.45 (s, 1 H, CH Ar-H), 4.64 (s, 1 H, CHCO),
2
2
7
.13–7.25 (m, 2 H, Ar-H), 7.28–7.36 (m, 2 H, Ar-H), 7.72–7.77 (m, 2 H, Ar-H), 8.11 (s, 1 H,
1
3
CH = N), 9.90 (s, 1 H, NH), 11.87 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-d ): δ 41.5
6
2
(
CH NH), 43.3 (CH), 44.2 (CHCO), 55.7 (CH N), 104.9 (C-NO ), 115.9 (d, J = 21
2
2
2
CF
2
1
Hz), 116.5 (d, J = 24 Hz), 128.8, 129.1, 129.8, 137.7, 144.9, 152.7, 161.8 (d, J = 239
CF
CF
1
Hz), 163.7 (d, J = 247 Hz), 165.2 (C = O), 169.4 (C = O).
CF
1
Minor diastereomer (26%), H NMR (300 MHz, DMSO-d ): δ 3.70 (s, 1 H, CH Ar-H),
6
3
.70–3.88 (m, 2 H, CH NH), 3.96–4.02 (m, 2 H, CH NH), 4.72 (s, 1 H, CHCO), 7.13–7.25
2 2
(
9
m, 2 H, Ar-H), 7.28–7.36 (m, 2 H, Ar-H), 7.72–7.77 (m, 2 H, Ar-H), 8.22 (s, 1 H, CH = N),
1
3
.90 (s, 1 H, NH), 11.92 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-d ): δ 41.5 (CH NH),
6 2
2
4
3.3 (CH), 44.2 (CHCO), 55.7 (CH N), 105.6 (C-NO ), 115.9 (d, J = 21 Hz), 116.5 (d,
2
2
CF
2
1
JCF = 24 Hz), 128.9, 129.7, 130.7, 137.7, 147.7, 153.8, 161.8 (d, J = 239 Hz), 163.7 (d,
CF
1
JCF = 247 Hz), 163.9 (C = O), 164.7 (C = O).
ꢀ
4
.2.14. (E)-N -(2-chlorobenzylidene)-7-(2-chlorophenyl)-8-nitro-5-oxo-1,2,3,5,6,7-
hexahydro-imidazo[1,2-a]pyridine-6-carbohydrazide (6n)
White solid: mp = 251–253°C, 0.225 g, yield 95%; IR (KBr) (ν¯max/cm−1): 3332 (NH), 3282
(
NH), 1694 and 1643 (C = O), 1444 and 1374 (NO ), 1204 (C–N), 1161 (C–N). Anal.
2
Calcd for C H C N O (474.30): C, 53.18; H, 3.61; N, 14.77.
2
1
17 l2
5
4

JOURNAL OF SULFUR CHEMISTRY
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1
Major diastereomer (53%), H NMR (300 MHz, DMSO-d ): δ 3.86–3.89 (m, 2 H,
6
CH NH), 4.00–4.02 (m, 2 H, CH N), 4.58 (s, 1 H, CH Ar-H), 4.97 (s, 1 H, CHCO),
2
2
7
1
4
1
1
.17–7.35 (m, 2 H, Ar-H), 7.40–7.53 (m, 2 H, Ar-H), 7.73–7.91 (m, 2 H, Ar-H), 8.44 (s,
1
3
H, CH = N), 9.94 (s, 1 H, NH), 12.04 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-d ): δ
6
3.5 (CH NH), 44.1 (CH), 51.1 (CHCO), 54.5 (CH N), 105.0 (C-NO ), 127.3, 127.8, 128.1,
2
2
2
28.3, 129.7, 130.4, 131.3, 132.0, 132.3, 132.8, 133.8, 139.1, 141.4, 152.5, 163.5 (C = O),
69.1 (C = O).
1
Minor diastereomer (47%), H NMR (300 MHz, DMSO-d ): δ 3.32 (s, 1 H, CH Ar-H),
6
δ 3.86–3.89 (m, 2 H, CH NH), 4.00–4.02 (m, 2 H, CH N), 5.05 (s, 1 H, CHCO), 7.17–7.35
2
2
(
m, 2 H, Ar-H), 7.40–7.53 (m, 2 H, Ar-H), 7.73–7.91 (m, 2 H, Ar-H), 8.63 (s, 1 H, CH = N),
13
9
4
1
.97 (s, 1 H, NH), 12.08 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-d ): δ 43.5 (CH NH),
6 2
4.1 (CH), 51.1 (CHCO), 54.5 (CH N), 105.3 (C-NO ), 127.3, 127.8, 128.1, 128.3, 129.7,
2
2
30.4, 131.3, 132.0, 132.3, 132.8, 133.6, 138.8, 145.1, 152.9, 163.4 (C = O), 164.1 (C = O).
ꢀ
4
.2.15. (E)-N -(4-chlorobenzylidene)-8-(4-chlorophenyl)-9-nitro-6-oxo-2,3,4,6,7,8-
hexahydro-1H-pyrido
[
1,2-a]pyrimidine-7-carbohydrazide (6o)
White solid: mp = 247–250°C, 0.347 g, yield 71%; IR (KBr) (ν¯max/cm−1): 3420 (NH), 3279
(
(
1
NH), 1695 and 1639 (C = O), 1447 and 1371 (NO ), 1158 (C–N). MS (EI, 70 eV): m/z
2
+
%) = 488 [M] , 276 (38), 261 (7), 248 (15), 165 (100), 154 (18), 138 (34), 127 (8), 111 (52),
02 (20), 89 (49), 75 (25), 50 (16). Anal. Calcd for C H Cl N O (488.32): C, 54.11; H,
22 19 2 5 4
3
.92; N, 14.34. Found: C, 54.6; H, 3.5; N, 14.1.
1
Major diastereomer 65%, H NMR (300 MHz, DMSO-d ): δ = 1.89–2.02 (m, 2 H,
6
CH ), 3.54, 3.61 (d, 2 H, CH NH), 3.98–4.00 (m, 2 H, CH N), 4.53 (s, 1 H, CH Ar-H)
2
2
2
4
1
.82 (s, 1 H, CHCO), 7.14–7.77 (m, 8 H, Ar-H), 8.11 (s, 1 H, HC = N), 11.51 (s, 1 H, NH),
13
1.90 (s, 1 H, NH). C NMR (75.4 MHz, DMSO-d ): δ 19.8 (CH ), 45.6 (HC-C = C), 47.8
6
2
(
CH -NH), 53.1 (CH -N), 54.6 (HCC = O), 106.6 (C-NO ), 128.8, 129.3, 129.4, 129.6,
2
2
2
1
32.6, 133.1, 135.4, 139.2, 145.1, 152.8, 166.1 (C = O), 168.9 (C = O).
1
Minor diastereomer 35%, H NMR (300 MHz, DMSO-d ): δ 1.89–2.02 (m, 2 H, CH ),
6
2
3
.54, 3.61 (d, 2 H, CH NH), 3.83 (s, 1 H, CH Ar-H), 3.98–4.00 (m, 2 H, CH N), 4.87 (s, 1
2
2
H, CH Ar-H), 7.14–7.77 (m, 8 H, Ar-H), 8.23 (s, 1 H, HC = N), 11.55 (s, 1 H, NH), 12.041
1
3
(
(
1
s, 1 H, NH). C NMR (75.4 MHz, DMSO-d ): δ 19.8 (CH ), 45.6 (HC-C = C), 47.8
6
2
CH -NH), 53.1 (CH -N), 54.6 (HCC = O), 107.1 (C-NO ), 129.2, 129.4, 129.6, 132.6,
2
2
2
33.1, 133.2, 135.4, 139.5, 147.6, 152.8, 163.7(C = O), 165.7 (C = O).
Disclosure statement
No potential conflict of interest was reported by the authors.
ORCID
Mohammad Bayat http://orcid.org/0000-0002-5235-1203
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