Synthesis, characterization, and biological screening of some novel thiazolidin-4-One and α-aminophosphonate derivatives

Article abstract of DOI:10.1080/10426507.2010.550268

Synthesis of some new functionalized thiazolidin-4-ones and α-amino phosphonate derivatives has been reported. The imines were synthesized from the reaction of various substituted anilines with 1-phenyl-3-(pyridine-4-yl)-1H- pyrazole-4-carbaldehyde in eth

Full text of DOI:10.1080/10426507.2010.550268

Phosphorus, Sulfur, and Silicon, 186:2021–2032, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.550268
SYNTHESIS, CHARACTERIZATION, AND BIOLOGICAL
SCREENING OF SOME NOVEL THIAZOLIDIN-4-ONE
AND α-AMINOPHOSPHONATE DERIVATIVES
P. V. Badadhe,1 N. M. Chavan,2 D. S. Ghotekar,2
P. G. Mandhane,2 R. S. Joshi,2 and C. H. Gill2
1PG Department of Chemistry, M.J.S. College, Shrigonda, Maharashtra, India
2Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University,
Aurangabad, India
GRAPHICAL ABSTRACT
Abstract Synthesis of some new functionalized thiazolidin-4-ones and α-amino phosphonate
derivatives has been reported. The imines were synthesized from the reaction of various substi-
tuted anilines with 1-phenyl-3-(pyridine-4-yl)-1H-pyrazole-4-carbaldehyde in ethanol at reflux
condition. The corresponding thiazolidin-4-ones and α-aminophosphonates were prepared by
reaction of imines with mercaptoacetic acid and triethyl phosphite, respectively. The structures
of the newly synthesized compounds were confirmed by IR, 1H NMR, and mass spectral data
and were evaluated for their antimicrobial activities.
Keywords 1-Phenyl-3-(pyridine-4-yl)-1H-pyrazole-4-carbaldehyde; imines; thiazolidin-4-
ones; α-aminophosphonates
Received 5 October 2010; accepted 15 December 2010.
The authors are thankful to the Head, Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada
University, Aurangabad-431004 (MS), and the Principal, M. J. S. College, Shrigonda, for their valuable guidance
and laboratory facility. They also thank the Department of Chemistry, University of Pune, India, for providing 1H
NMR and mass spectral data.
Address correspondence to Professor Charansingh Harnamsingh Gill, Ph.D., Department of Chem-
istry, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Aurangabad 431004, India. E-mail:
prof gill@rediffmail.com
2021

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P. V. BADADHE ET AL.
INTRODUCTION
Thiazolidin-4-one scaffold has been gaining prominence due to the fact that its
derivatives have been known to possess a wide spectrum of properties such as antibacte-
rial,1,2 antifungal,3,4 anticonvulsant,5,6 cox-1 inhibitor,7 antituberculosis,8–10 antihistamic,11
anticancer,12 and anti-HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI)13–15
activities. α-aminophosphonates have been the focus of attention in recent years because of
their structural analogy to the corresponding α-amino acids as well as heterocyclic phospho-
nates16 and ω-aminophosphonates.17 They act as peptide mimics,18 antibiotics, herbicides,19
pharmacological agents,20 and enzyme inhibitors.21 In addition, α-aminophosphonates have
broad application due to their antifungal22 and antibacterial activities.23
In our continuous program in the search of new potent and biologically active hetero-
cycles, we planned to synthesize some new series of various substituted thiazolidin-4-ones
and α-aminophosphonates and evaluated their antibacterial activity against the standard
drug Streptomycin.
RESULTS AND DISCUSSION
1-(Pyridine-4-yl) ethanone 1 reacted with phenyl hydrazine in ethanol to produce (E)-
2-phenyl-1-(1-(pyridine-4-yl)ethylidene)hydrazine24 2. Vilsmeier–Hack reaction on com-
pound 2 gives 1-phenyl-3-(pyridine-4-yl)-1H-pyrazole-4-carbaldehyde 3. Compound 3 on
reaction with the different substituted anilines in ethanol in the presence of catalytic amount
of acetic acid afforded corresponding imine derivatives 5a–h. The structures were assigned
for 5a–h based on elemental and spectral analyses. For example, the IR spectrum of the
isolated product 5a showed absorption at 1630 cm−1 (C N) and 1525 cm−1 (C N pyri-
1
dine). The H NMR spectrum of 5a reveled a singlet at δ 2.56 and δ 9.13 attributed to
methyl protons and CH N proton, respectively. A multiplet in the region δ 7.68 corre-
sponds to aromatic protons and pyrazole proton. Elemental analysis and mass spectral data
agree with the proposed structures for 5a–h. The imine derivatives 5a–h were allowed to
condense with mercapto acetic acid in dry dioxane and triethyl phosphite in ethanol under
acidic catalyst, thiazolidin-4-ones 6a–h, and α-aminophosphonates 7a–h were obtained
in good yield. Mechanistically, a role of HCl for the formation of α-aminophosphonates
has been proposed to protonate the imines that ultimately enhances the electrophilicity of
imines carbon. Then, subsequently, the lone pair of phosphorus of triethyl phosphite as a
phosphorus nucleophile attacks imines carbon to give phosphonium intermediate; finally,
the hydrolysis of phosphonium intermediate yields α-aminophosphonates and EtOH.25,26
The IR spectrum of 6a showed bands at 1700 and 1628 cm−1 due to N C O and
C N groups, respectively. The 1H NMR spectrum of 6a showed a singlet at δ 3.92 and δ 6.37
due to CH2 and CH protons of thiazolidin-4-one ring. The IR spectrum of 7a showed
absorption bands at 1230 and 1045 cm−1 due to P O and P O C2H5 groups, respectively.
The 1HNMR spectrum of 7a revealed a doublet of doublet at δ 4.79 and multiplet at δ 3.33
that were attributed to CH-P O and CH2 proton of α-aminophosphonates. Elemental
analysis and mass spectral data agree with the proposed structures 6a–h and 7a–h.
All the newly synthesized thiazolidin-4-ones and α-aminophosphonates were
screened for their antibacterial activities against Gram-positive Bacillus subtilis (ATCC
No. 6633), Staphylococcus aureus (ATCC No. 25923), and Gram-negative Salmonella
typhimurium (ATCC No. 23564), Pseudomonas aeruginosa (ATCC No. 27853) bacteria.

NOVEL THIAZOLIDIN-4-ONE AND α-AMINOPHOSPHONATE DERIVATIVES
Table 1 Physical data of synthesized compounds 5a–h, 6a–h, and 7a–h
2023
Entry
R1
R2
R3
Yield (%)
mp (◦C)
5a
5b
5c
5d
5e
5f
5g
5h
6a
6b
6c
6d
6e
6f
6g
6h
7a
7b
7c
7d
7e
7f
CH3
H
Cl
H
H
H
H
F
CH3
H
Cl
H
H
H
H
F
CH3
H
Cl
H
H
H
H
H
H
H
H
H
F
H
CH3
H
Cl
OCH3
F
F
F
H
CH3
H
Cl
OCH3
F
F
F
H
CH3
H
Cl
OCH3
F
75
69
72
65
58
73
81
64
67
73
67
65
76
64
71
69
58
63
78
83
64
73
67
66
140–142
210–212
172–174
189–191
198–201
245–247
195–197
233–235
295–297
275–277
300–3002
202–204
289–291
276–278
174–176
189–181
305–307
193–195
286–288
207–209
215–217
276–278
209–211
291–293
F
H
H
H
H
H
H
F
F
H
H
H
H
H
H
F
7g
7h
H
F
F
F
F
The compounds were dissolved in dimethyl sulfoxide (DMSO) at a concentration of
1 mg/mL. Antibacterial activity of DMSO against the test organisms was investigated and
was found to be nil. Molten nutrient agar (15 cm3) kept at 45 ◦C was then poured into the
Petri dishes and allowed to solidify. A total of 10-mL diameter holes were then punched
carefully using a sterile cork borer and completely filled with the test solutions. The plates
were incubated for 24 h at 37 ◦C. After 24 h, the inhibition zone that appeared around the
holes in each plate was measured. Antibacterial activity was determined by measuring the
diameter of inhibition zone and examining the minimum inhibitory concentration (MIC).
Activity of each compound was compared with streptomycin as standards. The observed
data of antibacterial activity of compounds and the standard drug are given in Table S1. The
compounds 6d, 6g, 7g, and 7h show excellent antibacterial activity against Gram-positive
bacterial strains. Likewise, compounds 6g, 6h, and 7e showed excellent activity against
Gram-negative bacterial strains.
EXPERIMENTAL
Melting points were determined in an open capillary in liquid paraffin bath and were
uncorrected. The progress of reaction was monitored by thin layer chromatography (TLC)
using silica gel (Merck). IR spectra were recorded on a SHIMADZU–FT-IR spectropho-
1
tometer in KBr disc. H NMR spectra were recorded on BRUKER ADVANCE–II 400
NMR spectrometer in DMSO-d6/CDCl3 as a solvent and tetramethylsilane (TMS) as an
internal standard. Chemical shifts are given in δ ppm. Mass spectra were recorded on a

2024
P. V. BADADHE ET AL.
Table S1 The MIC of tested compounds 6a–h and 7a–h in µg/mL
Tested
compounds
B. subtilis
ZIa (MIC)b
S. aureus
ZIa (MIC)b
S. typhi
ZIa (MIC)b
P. aeroginosa
ZIa (MIC)b
6a
6b
6c
6d
6g
6h
7a
7b
7c
7d
7e
7g
15 (15)
16 (15)
18 (15)
17 (10)
19 (10)
14 (15)
15 (15)
13 (15)
13 (15)
14 (15)
17 (15)
18 (10)
19 (10)
22 (10)
16 (15)
21 (15)
20 (15)
22 (10)
23 (10)
20 (15)
19 (15)
15 (15)
14 (15)
16 (15)
19 (15)
16 (15)
18 (15)
24 (10)
12 (15)
15 (15)
13 (15)
13 (15)
16 (15)
19 (10)
7 (15)
5 (15)
9 (15)
8 (10)
10 (15)
16 (15)
15 (15)
17 (15)
19 (10)
18 (10)
10 (15)
7 (15)
11 (15)
7 (15)
16 (15)
15 (15)
13 (15)
19 (10)
18 (10)
17 (15)
14 (15)
20 (10)
7h
Streptomycin
aZone of inhibition. bMIC in µg/mL.
PEP-SCIUX-APIQ pulsar (electron preionization) mass spectrometer. Elemental analyses
were performed on Perkin-Elmer EAL-240 elemental analyzer.
General Procedure for the Synthesis of
1-phenyl-3-(pyridine-4-yl)-1H-pyrazole-4-carbaldehyde 3
A solution of 1-(Pyridine-4-yl) ethanone 1 (1 mmol) and phenyl hydrazine (1 mmol)
in absolute ethanol (25 mL) containing catalytic amount of sulfuric acid (0.1 mL) was
stirred at room temperature for 10 min. The yellow colored solid thus obtained was filtered,
washed with cold ethanol, and dried under vacuum to get the compound 2. To a stirred
solution of dimethylformamide (DMF) (1 mmol), phosphorus oxychloride (6 mmol) was
added at 0 ◦C and the reaction mixture was stirred at room temperature for 30 min. Then,
the (E)-2-phenyl-1-(1-(pyridine-4-yl)ethylidene)hydrazine 2 (2 mmol) was added at 0 ◦C
and the reaction mixture was stirred overnight at room temperature. The resultant contents
were poured onto crushed ice; solid product was separated by filtration and washed with
cold sodium bicarbonate solution (10%) followed by water and crystallized from ethanol.
O
N
NH
Ph-NH-NH2
N
DMF/POCl3
N
AcOH, ethanol
N
CHO
N
N
1
2
3
Scheme 1

NOVEL THIAZOLIDIN-4-ONE AND α-AMINOPHOSPHONATE DERIVATIVES
2025
NH2
R1
R2
N
N
AcOH, ethanol
reflux
3
R1
R2
R3
N
R3
N
5a--h
N
N
N
N
S
R1
mercaptoacetic acid
dry dioxane
triethylphosphite
HCl
5a--h
R2
R3
N
O
N
HN
N
P
O
O
O
R1
R3
R2
6a--h
7a--h
Scheme 2
Spectral and Analytical Data of Compound 3
3: 1H NMR (DMSO-d6), δ ppm = 10.2 (s, 1H, CHO), 8.75 (d, 2H, J = 4.65 Hz,
C-2 and C-6 pyridine ring protons), 8.49 (s, 1H, pyrazole proton), 7.38 (m, 7H, Ar-H); IR
(KBr discs cm−1), 2765 ( CHO), 1735 ( C O), 1520 ( C N, pyridine); ES-MS, m/z:
249. Anal. calcd. for C15H11N3O (249.27): C, 72.28%; H, 4.45%, N, 16.86%. Found: C,
72.25%; H, 4.37%, N, 16.97%.
General Procedure for the Synthesis of 5a–h
An equimolar mixture of 1-phenyl-3-(pyridine-4-yl)-1H-pyrazole-4-carbaldehyde 3
(4 mmol) and different substituted anilines 4a–h (4 mmol) in ethanol (10 mL) containing
catalytic amount of glacial acetic acid (0.5 mL) was refluxed for 3–5 h. The progress
of reaction was monitored by TLC (solvent system—hexane:ethyl acetate, 9:1). After
completion of reaction, the excess of solvent was evaporated under vacuum. The separated
solid was filtered off, washed well with water followed with cold ethanol, and crystallized
from ethanol.
Spectral and Analytical Data of Compounds 5a–h
5a: 1H NMR (DMSO-d6), δ ppm = 9.13 (s, 1H, CH N), 8.73 (d, 2H, C-2 and C-6
pyridine ring protons), 8.21 (d, 2H, Ar-H), 7.65 (2H, d, J = 5.5 Hz, Ar-H), 7.68 (6H, m,
Ar-H and pyrazole protons), 7.03 (d, 2H, J = 8.59 Hz, Ar-H), 2.56 (s, 3H, CH3); IR (KBr
discs, cm−1), 1627 (C N), 1523 (C N, pyridine); ES-MS, m/z: 339.20. Anal. calcd. for
C22H18N4 (338.41): C, 78.08%; H, 5.36%, N, 16.56%. Found: C, 78.15%; H, 5.27%, N,
16.59%.

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P. V. BADADHE ET AL.
Figure S1 1H NMR spectrum of 5a.
Figure S2 1H NMR spectrum of 6a.

NOVEL THIAZOLIDIN-4-ONE AND α-AMINOPHOSPHONATE DERIVATIVES
2027
Figure S3 1H NMR spectrum of 7a.
5b: 1H NMR (DMSO-d6), δ ppm = 8.94 (s, 1H, CH N), 8.79 (d, 2H, C-2 and C-6
pyridine ring protons), 7.98 (2H, d, J = 5 Hz, Ar-H), 7.88 (d, 2H, J = 8.5 Hz, Ar-H), 7.35
(m, 6H, Ar-H and pyrazole protons), 7.11 (d, 2H, J = 7.69 Hz, Ar-H), 2.37 (s, 3H, CH3);
IR (KBr discs, cm−1), 1637 (C N), 1595 (C N, pyridine); ES-MS, m/z: 339.28. Anal.
calcd. for C22H18N4 (338.41): C, 78.08%; H, 5.36%; N, 16.56%. Found: C; 78.24%; H,
5.32%; N, 16.50%.
Figure S4 31H NMR spectrum of 7a.

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P. V. BADADHE ET AL.
1
5c: H NMR (DMSO-d6), δ ppm = 8.89 (s, 1H, CH N), 8.76 (d, 2H, C-2 and
C-6 pyridine protons), 7.73 (d, 2H, J = 5.5 Hz, Ar-H), 7.15 (m, 10H, Ar-H and pyrazole
protons); IR (KBr discs, cm−1), 1632 (C N), 1576 (C N, pyridine); ES-MS, m/z: 359.70.
Anal. calcd. for C21H15ClN4 (358.82): C, 70.29%; H, 4.21%; N, 15.61%. Found: C, 70.24%;
H, 4.32%; N, 15.56%.
5d: 1H NMR (DMSO-d6), δ ppm = 8.85, (s, 1H, CH N), 8.69 (d, 2H, C-2 and C-6
pyridine protons), 7.85 (d, 2H, J = 8 Hz, Ar-H), 7.52 (d, 2H, J = 5 Hz, Ar-H), 7.38 (m, 6H,
Ar-H and pyrazole protons), 7.23 (d, 2H, J = 8.5 Hz); IR (KBr discs cm−1), 1625 (C N),
1568 (C N, pyridine); ES-MS, m/z: 359.45. Anal. calcd. for C21H15ClN4 (358.82): C,
70.29%; H, 4.21%; N, 15.61%. Found: C, 70.32%; H, 4.38%; N, 15.63%.
1
5e: H NMR (CDCl3), δ ppm = 8.78 (s, 1H, CH N), 8.67 (d, 2H, C-2 and C-6
pyridine protons), 7.79 (d, 2H, J = 5 38 Hz, Ar-H), 7.65 (d, 2H, J = 8.5 Hz, Ar-H), 7.45
(m, 6H, Ar-H and pyrazole protons), 7.15 (d, 2H, J = 7.8 Hz, Ar-H), 3.59 (s, 3H, OCH3);
IR (KBr discs cm−1), 1634 (C N), 1580 (C N, pyridine); ES-MS, m/z: 354. Anal. calcd.
for C22H18N4O (354.15): C, 74.56%; H, 5.12%; N, 15.81%. Found: C, 74.72%; H, 5.18%;
N, 15.63%.
1
5f: H NMR (DMSO-d6), δ ppm = 8.77 (s, 1H, CH N), 8.76 (d, 2H, C-2 and
C-6 pyridine protons), 7.81 (d, 2H, J = 5.5 Hz, Ar-H), 7.73 (d, 2H, J = 8. Hz, Ar-H),
7.22 (d, 2H, J = 7.74 Hz, Ar-H), 7.23 (m, 6H, Ar-H and pyrazole protons); IR (KBr discs
cm−1), 1655 (C N), 1576 (C N, pyridine); ES-MS, m/z: 342. Anal. calcd. for C21H15FN4
(342.51): C, 73.67%; H, 4.42%; N, 16.36%. Found: C, 73.52%; H, 4.45%; N, 16.53%.
1
5g: H NMR (CDCl3), δ ppm = 8.92 (s, 1H, CH N ), 8.73 (d, 2H, C-2 and C-6
pyridine protons), 7.89 (2H, d, J = 5 Hz, Ar-H), 7.13 (m, 9H, Ar-H and pyrazole proton);
IR (KBr discs cm−1), 1628 (C N), 1555 (C N, pyridine); ES-MS, m/z: 360.50. Anal.
calcd. for C21H14F2N4 (360.12): C, 69.99%; H, 3.92%; N, 15.55%. Found: C, 70.12%; H,
3.98%; N, 15.38%.
5h: 1H NMR (CDCl3), δ ppm = 8.85 (d, 2H, C-2 and C-6 pyridine protons), 8.68 (s,
1H, CH N ), 7.76 (2H, d, J = 5.37 Hz, Ar-H), 7.17 (8H, m, Ar-H and pyrazole proton);
IR (KBr discs cm−1), 1636 (C N), 1558 (C N, pyridine); ES-MS, m/z: 378. Anal. calcd.
for C21H13F3N4 (378.11): C, 66.66%; H, 3.46%; N, 14.81%. Found: C, 66.52%; H, 3.68%;
N, 14.93%.
General Procedure for the Synthesis of 6a–h
A solution of compounds 5a–h (1.5 mmol) and mercaptoacetic acid (3 mmol) in dry
dioxane (5) was refluxed for 6–7 h. The progress of the reaction was monitored on TLC
using hexane:ethyl acetate (8:2) as the solvent system. After completion of reaction, the
solvent was evaporated under vacuum and residue was washed with 4 N Na2CO3 solution
followed with water. The separated solid was filtered off, washed with water till carbonate
free, and then with ether, and crystallized from ethanol.
Spectral and Analytical Data of Compounds 6a–h
6a: 1H NMR (CDCl3), δ ppm = 8.70 (d, 2H, C-2 and C-6 pyridine ring protons, J =
4.50 Hz), 8.02 (s, 1H, pyrazoyl proton), 7.65 (d, 2H, J = 7.9 Hz, Ar-H), 7.28 (7H, m,
Ar-H), 6.96 (d, 2H, J = 8 Hz, Ar-H), 6.37 (s, 1H, CH proton of thiazolidinone ring),
3.92 (s, 2H, -S-CH2-CO proton), 2.28 (s, 3H, CH3); IR (KBr discs, cm−1), 3050 (C H,

NOVEL THIAZOLIDIN-4-ONE AND α-AMINOPHOSPHONATE DERIVATIVES
2029
Ar), 1700 (N C O), 1628 (C N); ES-MS, m/z: 413.41. Anal. calcd. for C24H20N4OS
(412.51): C, 69.88%; H, 4.89%; N, 13.58%; S, 7.77%. Found: C, 69.77%; H, 4.93%; N,
13.52%; S,7.84%.
6b: 1H NMR (CDCl3), δ ppm = 8.76 (d, 2H, C-2 and C-6 pyridine ring protons, J =
4.8 Hz), 8.11 (s, 1H, pyrazoyl proton), 7.59 (d, 2H, J = 8.2 Hz, Ar-H), 7.18 (d, 2H, J =
8.5 Hz), 7.32 (m, 5H, Ar-H), 6.82 (d, 2H, J = 8.3 Hz, Ar-H), 6.39 (s, 1H, CH proton of
thiazolidinone ring), 3.73 (s, 2H, S CH2 CO- proton), 2.38 (s, 3H, CH3); IR (KBr discs,
cm−1), 3088 (C H, Ar), 1720 (N C O), 1602 (C N); ES-MS, m/z: 413.61. Anal. calcd.
for C24H20N4OS (412.51): C, 69.88%; H, 4.89%; N, 13.58%; S, 7.77%. Found: C, 69.77%;
H, 4.93%; N, 13.52%; S, 7.84%.
1
6c: H NMR (CDCl3), δ ppm = 8.70 (d, 2H, C-2 and C-6 pyridine ring protons,
J = 4.93 Hz), 8.11 (s, 1H, pyrazoyl proton), 7.71 (d, 2H, J = 8.38 Hz, Ar-H), 7.22 (m,
9H, Ar-H), 6.34 (s, 1H, CH proton of thiazolidinone ring), 3.70 (s, 2H, S CH2 CO-
proton); IR (KBr discs, cm−1), 3150 (C H, Ar), 1705 (N C O), 1639 (C N); ES-MS,
m/z: 433.30. Anal. calcd. for C23H17ClN4OS (432.93): C, 63.81%; H, 3.96%; N, 12.94%;
S, 7.41%. Found: C, 63.78%; H, 3.98%; N, 13.05%; S, 7.54%.
6d: 1H NMR (CDCl3), δ ppm = 8.73 (d, 2H, C-2 and C-6 pyridine ring protons, J =
4.53 Hz), 8.05 (s, 1H, pyrazoyl proton), 7.67 (d, 2H, J = 7.9 Hz, Ar-H), 7.32 (m, 5H, Ar-H),
7.23 (d, 2H, J = 8.4 Hz), 6.97 (d, 2H, J = 8.5 Hz, Ar-H), 6.37 (s, 1H, CH proton of
hiazolidinone ring), 3.74 (s, 2H, S CH2 CO- proton); IR (KBr discs, cm−1), 3059 (C H,
Ar), 1715 (N C O), 1655 (C N); ES-MS, m/z: 433.20. Anal. calcd. for C23H17ClN4OS
(432.93): C, 63.81%; H, 3.96%; N, 12.94%; S, 7.41%. Found: C, 63.78%; H, 3.98%; N,
13.05%; S, 7.54%.
6e: 1H NMR (CDCl3), δ ppm = 8.73 (d, 2H, C-2 and C-6 pyridine ring protons, J =
4.77 Hz), 8.07 (s, 1H pyrazoyl proton), 7.59 (d, 2H, J = 8.2 Hz, Ar-H), 7.30 (m, 5H,
Ar-H), 7.18 (d, 2H, J = 8.5 Hz), 6.72 (d, 2H, J = 8.3 Hz, Ar-H), 6.41 (s, 1H, CH proton
of thiazolidinone ring), 3.98 (s, 2H, S CH2 CO-proton), 3.34 (s, 3H, OCH3); IR (KBr
discs, cm−1), 3115 (C H, Ar), 1725 (N C O), 1623 (C N); ES-MS, m/z: 429.10. Anal.
calcd. for C24H20N4O2S (428.51): C, 67.27%; H, 4.70%; N, 13.07%; S, 7.48%. Found: C,
67.19%; H, 4.72%; N, 12.98%; S, 7.56%.
1
6f: H NMR (CDCl3), δ ppm = 8.78 (d, 2H, C-2 and C-6 pyridine ring proton, J
= 4.48 Hz), 8.14 (s, 1H pyrazoyl proton), 7.63 (d, 2H, J = 8.5 Hz, Ar-H), 7.25 (d, 2H,
J = 8.3 Hz), 7.41(m, 5H, Ar-H), 6.78 (d, 2H, J = 8.4 Hz, Ar-H), 6.40 (s, 1H, CH
proton of thiazolidinone ring), 4.05 (s, 2H, S CH2 CO- proton); IR (KBr discs, cm−1),
3063 (C H, Ar-H), 1696 (N C O), 1627 (C N); ES-MS, m/z: 417.30. Anal. calcd. for
C23H17FN4O3S (416.47): C, 66.33%; H, 4.11%; N, 13.45%; S, 7.70%. Found: C, 66.28%;
H, 4.23%; N, 13.36%; S, 7.88%.
6g: 1H NMR (CDCl3), δ ppm = 8.78 (d, 2H, C-2 and C-6 pyridine ring proton, J =
4.68 Hz), 8.17 (s, 1H pyrazoyl proton), 7.73 (d, 2H, J = 8.5, Ar-H), 7.35 (m, 6H, Ar-H),
7.19 (d, 2H, J = 8.2, Ar-H), 6.35 (s, 1H, CH proton of thiazolidinone ring), 3.97 (s,
2H, S CH2 CO- proton); IR (KBr discs, cm−1), 3070 (C H, Ar), 1696 (N C O), 1637
(C N); ES-MS, m/z: 437.60. Anal. calcd. for C23H16F2N4OS (434.46): C, 66.58%; H,
3.71%; N, 12.90%; S, 7.12%. Found: C, 66.45%; H, 3.66%; N, 13.05%; S, 7.45%.
6h: 1H NMR (DMSO-δ6), δ ppm = 8.68 (d, 2H, C-2 and C-6 pyridine ring proton, J
= 4.20 Hz), 8.10 (s, 1H, pyrazoyl proton), 7.65 (d, 2H, J = 8.2, Ar-H), 7.23 (m, 7H, Ar-H),
6.44 (s, 1H, CH proton of thiazolidinone ring), 3.92 (s, S CH2 CO- proton); IR (KBr
discs, cm−1), 3055 (C H, Ar), 1700 (N C O), 1608 (C N); ES-MS, m/z: 453.30. Anal.

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P. V. BADADHE ET AL.
calcd. for C23H15F3N4OS (452.09): C, 61.06%; H, 3.34%; N, 12.38%; S, 7.09%. Found:
C, 61.02%; H, 3.47%; N, 12.57%; S, 7.21%.
General Procedure for the Synthesis of 7a–h
A solution of compounds 5a–h (1.5 mmol) and triethyl phosphite (3 mmol) in ethanol
containing conc. HCl (0.5 mL) was stirred at room temperature for 10–15 min. After
completion of the reaction (checked by TLC), the reaction mixture was poured onto crushed
ice and neutralized with 1:1 ammonia. The separated solid was filtered off, washed with
water, and crystallized from ethanol.
Spectral and Analytical Data of Compounds 7a–h
7a: 1H NMR (CDCl3), δ ppm = 8.86 (d, 2H, C-2 and C-6 pyridine ring protons), 8.45
(s, 1H, pyrazoyl proton), 7.75 (m, 7H, Ar-H), 7.14 (d, 2H, J = 8.3 Hz, Ar-H), 6.57 (d, 2H,
J = 8 Hz, Ar-H), 4.79 (dd, 2JPH = 20.6 Hz, 8.3 Hz CH proton), 4.33 (m, 4H), 3.49 (t,
1H, J = 7.59 Hz, 1H, NH), 2.40 (s, 3H, CH3), 1.31 (t, 3H, J = 7.3 Hz), 1.22 (t, 3H, J = 6.9
Hz); 31P NMR (CDCl3), δ ppm = 23.68; IR (KBr discs, cm−1), 3155 (N-H), 2940 (C H
alkane), 1230 (P O), 1045 (P-O-Et), ES-MS, m/z: 477. Anal. calcd. for C26H29N4O3P
(476.51): C, 65.53%; H, 6.13%; N, 11.76%. Found: C, 65.43%; H, 6.15%; N, 11.73%.
1
7b: H NMR (CDCl3), δ ppm = 8.91 (d, 2H, C-2 and C-6 pyridine ring protons),
8.43 (s, 1H, pyrazoyl proton), 7.87 (d, 2H, J = 6.36 Hz, Ar-H), 7.26 (m, 7H, Ar-H), 6.48
(d, 2H, J = 6.2 Hz, Ar-H), 4.68 (dd, 1H, 2JPH = 20.9 Hz, 8.5 Hz), 4.21 (m, 4H), 3.49 (t,
1H, J = 7.09 Hz, NH), 2.25 (s, 3H, CH3), 1.42 (t, 3H, J = 7.1 Hz), 1.29 (t, 3H, J = 6.7
Hz); 31P NMR (CDCl3), δ ppm = 25.82; IR (KBr discs, cm−1), 3206 (N-H), 2940 (C H
alkane), 1230 (P O), 1105 (P-O-Et), ES-MS, m/z: 477.30. Anal. calcd. for C26H29N4O3P
(476.51): C, 65.53%; H, 6.13%; N, 11.76%. Found: C, 65.43%; H, 6.15%; N, 11.73%.
1
7c: H NMR (CDCl3), δ ppm = 8.89 (d, 2H, C-2 and C-6 pyridine ring protons),
8.51 (s, 1H, pyrazoyl proton), 7.78 (d, 2H, J = 6.4 Hz, Ar-H), 7.39 (m, 9H, Ar-H), 4.86
(dd, 1H, 2JPH = 19.9 Hz, 8.1 Hz), 4.52 (t, 1H, J = 7.25 Hz, NH), 4.24 (m, 4H), 1.46 (t,
3H, J = 7.3 Hz), 1.32 (t, 3H, J = 6.8 Hz); 31P NMR (CDCl3), δ ppm = 23.82; IR (KBr
discs, cm−1), 3208 (N-H), 2940 (C H alkane), 1238 (P O), 1056 (P-O-Et), ES-MS, m/z:
497. Anal. calcd. for C25H26ClN4O3P (496.93): C, 60.43%; H, 5.27%; N, 11.27%. Found:
C, 60.35%; H, 5.30%; N, 11.25%.
1
7d: H NMR (CDCl3), δ ppm = 8.80 (d, 2H, C-2 and C-6 pyridine ring protons),
8.58 (s, 1H, pyrazoyl proton), 7.78 (d, 2H, J = 6 Hz, Ar-H), 7.31 (m, 5H, Ar-H), 7.09 (d,
2
2H, J = 8.5 Hz, Ar-H), 6.53 (d, 2H, J = 6.3 Hz, Ar-H), 4.92 (dd, 1H, JPH = 18.8 Hz,
8.3 Hz),4.43 (t, 1H, NH, J = 7.19 Hz), 4.28 (m, 4H), 1.52 (t, 3H, J = 7.1 Hz), 1.27 (t, 3H,
J = 6.7 Hz); 31P NMR (DMSO-d6), δ ppm = 27.82; IR (KBr discs, cm−1), 3208 (N-H),
2965 (C H alkane), 1235 (P O), 1123 (P-O-Et), ES-MS, m/z: 497.10. Anal. calcd. for
C26H29ClN4O3P (496.93): C, 60.43%; H, 5.27%; N, 11.27%. Found: C, 60.35%; H, 5.30%;
N, 11.25%.
1
7e: H NMR (CDCl3), δ ppm = 8.84 (d, 2H, C-2 and C-6 pyridine ring protons),
8.47 (s, 1H, pyrazoyl proton), 7. 81 (d, 2H, J = 6.3 Hz, Ar-H), 7.35 (m, 5H, Ar-H), 7.05 (d,
2H, J = 8.79 Hz, Ar-H), 6.42 (d, 2H, J = 6 Hz, Ar-H), 4.88 (dd, 1H, 2JPH = 19.2 Hz, 8.5
Hz), 4.47 (t, 1H, NH, J = 7.4 Hz), 4.25 (m, 4H), 3.31 (s, 3H, -OCH3), 1.55 (t, 3H, J = 7.4
Hz), 1.30 (t, 3H, J = 6.8 Hz); 31P NMR (CDCl3), δ ppm = 22.78;IR (KBr discs, cm−1),
3238 (N-H), 2930 (C H alkane), 1244 (P O), 1113 (P-O-Et); ES-MS, m/z: 492. Anal.

NOVEL THIAZOLIDIN-4-ONE AND α-AMINOPHOSPHONATE DERIVATIVES
2031
calcd. for C26H29N4O4P (492.51): C, 63.41%; H, 5.93%; N, 11.38%. Found: C, 63.38%;
H, 5.89%; N, 11.37%.
7f: 1H NMR (CDCl3), δ ppm = 8.78 (d, 2H, C-2 and C-6 pyridine ring protons), 8.54
(s, 1H, pyrazoyl proton), 7.87 (d, 2H, J = 6.69 Hz, Ar-H), 7.24 (m, 5H, Ar-H), 7.15 (d, 2H,
J = 8.3 Hz, Ar-H), 6.57 (d, 2H, J = 8.4 Hz, Ar-H), 4.94 (dd, 1H, 2JPH = 19.3 Hz, 7.1 Hz),
4.55 (t, 1H, J = 7.3 Hz, NH), 4.32 (m, 4H), 1.46 (t, 3H, J = 7.1 Hz), 1.28 (t, 3H, J = 6.7
Hz); 31P NMR (CDCl3), δ ppm = 26.81;IR (KBr discs, cm−1), 3208 (N-H), 2946 (C H
alkane), 1235 (P O), 1123 (P-O-Et); ES-MS, m/z: 481. Anal. calcd. for C25H26FN4O3P
(480.47): C, 62.49%; H, 5.45%; N, 11.66%. Found: C, 62.39%; H, 5.46%; N, 11.65%.
7g: 1H NMR (CDCl3), δ ppm = 8.75 (d, 2H, C-2 and C-6 pyridine ring protons), 8.57
(s, 1H, pyrazoyl proton), 7.81 (d, 2H, J = 6.69 Hz, Ar-H), 7.45 (m, 6H, Ar-H), 6.48 (d,
2H, J = 6.2 Hz, Ar-H), 4.98 (dd, 1H, 2JPH = 18.9 Hz, 7.6 Hz), 4.61 (s, 1H, J = 7.24 Hz,
NH), 4.29 (m, 4H), 1.52 (t, 3H, J = 7.3 Hz), 1.31 (t, 3H, J = 6.7 Hz); 31P NMR (CDCl3),
δ ppm = 24.10; IR (KBr discs, cm−1), 3208 (N-H), 2966 (C H alkane), 1246 (P O),
1123 (P-O-Et); ES-MS, m/z: 499. Anal. calcd. for C25H25F2N4O3P (498.46): C, 60.24%;
H, 5.06%; N, 11.24%. Found: C, 60.16%; H, 5.08%; N, 11.22%.
1
7h: H NMR (CDCl3), δ ppm = 8.79 (d, 2H, C-2 and C-6 pyridine ring protons),
8.45 (s, 1H, pyrazoyl proton), 7.45 (m, 7H, Ar-H), 6.51 (d, 2H, J = 6 Hz, Ar-H), 5.03 (dd,
1H, 2JPH = 19.8 Hz, 8.5 Hz), 4.56 (s, 1H, 7.4 Hz, NH), 4.34 (m, 4H), 1.45 (t, 3H, J = 7.1
Hz), 1.29 (t, 3H, J = 6.5 Hz); 31P NMR (CDCl3), δ ppm = 23.88; IR (KBr discs, cm−1),
3250 (N-H), 2950 C H alkane), 1256 (P O), 1134 (P-O-Et); ES-MS, m/z: 517.40. Anal.
calcd. for C25H24F3N4O3P (516.45): C, 58.14%; H, 4.68%; N, 10.85%. Found: C, 58.07%;
H, 4.65%; N, 10.01%.
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