One-pot synthesis of pyrimidinothiazolidinones and their anti-inflammatory and antimicrobial studies

Article abstract of DOI:10.1080/10426500902839384

In the present investigation, we report a one-pot synthesis of the title compounds, 2-arylidene-5-(2,3,6-trimethyl-4-methoxyphenyl)-7-substituted-5H- pyrimidino-[2,3-b]thiazolidine-3-ones 6a-j and 2-(5-nitro-2-thienylidine)-5-(2, 3,6-trimethyl-4-methoxyphenyl)-7-substituted-5H- pyrimidino-[2,3-b]thiazolidine- 3-ones 7a-e. Thus, 6a-j and 7a-e were prepared in good yields by refluxing 4-(2,3,6-trimethyl-4-methoxyphenyl)-6-methyl/aryl-3,4-dihydropyrimidin-2-(1H) -thiones 5, monochloro acetic acid, and anhydrous sodium acetate with the appropriate aromatic aldehyde/5-nitro-2-thiophenediacetate in acetic acid/acetic anhydride medium. The structures of these new compounds were established on the basis of their analytical and spectral data. Some of the newly synthesized compounds were screened for their anti-inflammatory and antimicrobial activity. They show moderate anti-inflammatory activity, and some of them were found to be promising antibacterial and antifungal agents. Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.

Full text of DOI:10.1080/10426500902839384

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One-Pot Synthesis of
Pyrimidinothiazolidinones and Their
Anti-Inflammatory and Antimicrobial
Studies
B. Lingappa a , K. V. Sujith b , Adithya Adhikari b , N. Satheesha Rai b
, K. Vijaynarayana c & Balakrishna Kalluraya b
a Strides Research and Specialty Chemicals Ltd , Mangalore,
Karnataka, India
b Department of Studies in Chemistry , Mangalore University ,
Mangalagangothri, Karnataka, India
c Department of Pharmacology , NGSM Institute of Pharmaceutical
Science , Deralakatte, Karnataka, India
Published online: 24 Feb 2010.
To cite this article: B. Lingappa , K. V. Sujith , Adithya Adhikari , N. Satheesha Rai , K. Vijaynarayana
& Balakrishna Kalluraya (2010) One-Pot Synthesis of Pyrimidinothiazolidinones and Their Anti-
Inflammatory and Antimicrobial Studies, Phosphorus, Sulfur, and Silicon and the Related Elements,
185:3, 501-508, DOI: 10.1080/10426500902839384
To link to this article: http://dx.doi.org/10.1080/10426500902839384
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Phosphorus, Sulfur, and Silicon, 185:501–508, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902839384
ONE-POT SYNTHESIS OF
PYRIMIDINOTHIAZOLIDINONES AND THEIR
ANTI-INFLAMMATORY AND ANTIMICROBIAL STUDIES
B. Lingappa,1 K. V. Sujith,2 Adithya Adhikari,2
N. Satheesha Rai,2 K. Vijaynarayana,3
and Balakrishna Kalluraya2
1Strides Research and Specialty Chemicals Ltd, Mangalore, Karnataka, India
2Department of Studies in Chemistry, Mangalore University, Mangalagangothri,
Karnataka, India
3Department of Pharmacology, NGSM Institute of Pharmaceutical Science,
Deralakatte, Karnataka, India
In the present investigation, we report a one-pot synthesis of the title compounds, 2-arylidene-
5-(2,3,6-trimethyl-4-methoxyphenyl)-7-substituted-5H-pyrimidino-[2,3-b]thiazolidine-3-ones
6a–j and 2-(5-nitro-2-thienylidine)-5-(2,3,6-trimethyl-4-methoxyphenyl)-7-substituted-5H-
pyrimidino-[2,3-b]thiazolidine-3-ones 7a–e. Thus, 6a–j and 7a–e were prepared in good
yieldsbyrefluxing4-(2,3,6-trimethyl-4-methoxyphenyl)-6-methyl/aryl-3,4-dihydropyrimidin-
2-(1H)-thiones 5, monochloro acetic acid, and anhydrous sodium acetate with the
appropriate aromatic aldehyde/5-nitro-2-thiophenediacetate in acetic acid/acetic anhydride
medium. The structures of these new compounds were established on the basis of their
analytical and spectral data. Some of the newly synthesized compounds were screened for
their anti-inflammatory and antimicrobial activity. They show moderate anti-inflammatory
activity, and some of them were found to be promising antibacterial and antifungal agents.
Supplemental materials are available for this article. Go to the publisher’s online edition of
Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental
file.
Keywords Anti-inflammatory and antimicrobial activity; multicomponent reaction; 5-nitro-2-
thiophenaldiacetate; pyrimidinones
INTRODUCTION
Multicomponent reactions (MCR) are special types of theoretically useful organic
reactions in which three or more starting materials react to give a product.1 Convergent
synthetic pathways generally show advantages over linear or divergent approaches with
Received 6 October 2008; accepted 22 February 2009.
The authors are thankful to the Managing Director, Strides Research and Specialty Cauhemicals Ltd., New
Mangalore, India, for providing laboratory facilities. Thanks are also due to SAIF, CDRI, Lucknow, India, for
providing 1H NMR and mass spectral analysis.
Address correspondence to Balakrishna Kalluraya, Department of Studies in Chemistry, Mangalore Univer-
sity, Mangalagangothri-574 199, Karnataka, India. E-mail: bkalluraya@gmail.com
501

502
B. LINGAPPA ET AL.
respect to time, speed, yield, and reproducibility. Among organic reactions, MCR with
more than two starting materials are assembled to afford a complex product. Therefore,
they constitute a superior tool for diversity-oriented and complexity-generating synthesis for
drug discovery.2,3 Well known examples for the synthesis of heterocycles through MCR are
the Biginelli reaction4 and the Hantzsch dihydropyridine synthesis.5 Pyrimidine derivatives
are known for their varied biological properties.6–8 Thiazoles and their derivatives are found
to be associated with various biological activities such as antibacterial, antifungal, and anti-
inflammatory activities.9–11 Prompted by the biological and pharmacological applications
of thiazolidinone derivatives and in view of the diversity of MCRs, we planned to synthesize
a series of thiazolidinone derivatives containing a pyrimidine nucleus. The results of such
experiments including the synthesis, characterization, and biological studies of these newly
synthesized thiazolidinone derivatives are reported in this article.
RESULTS AND DISCUSSION
The synthetic route followed for obtaining the title compound is outlined in Scheme
1. Vilsmeier–Haack reaction of 1-methoxy-2,3,5-trimethylbenzene 2 with phosphorous
oxychloride and dimethyl formamide produced 2,3,6-trimethyl-4-methoxybenzaldehyde
3, whereas 1-methoxy-2,3,5-trimethylbenzene 2 was in turn obtained by the methyla-
tion of 2,3,5-trimethylphenol 1 using methyl iodide in ethanol medium in the presence
of potassium hydroxide as a catalyst. Chalcones 4 were prepared by condensing 2,3,6-
trimethyl-4- methoxybenzaldehyde 3 with the appropriate ketone in the presence of sodium
hydroxide under the Clasein–Schmidt reaction conditions. However 4-(2,3,6-trimethyl-4-
methoxyphenyl)-3-butene-2-one 4a was prepared by the condensation of 2,3,6-trimethyl-
4-methoxybenzaldehyde 3 with acetone as described in the literature.12 The character-
ization data of these chalcones are given in Table I. When these chalcones 4 were
treated with thiourea in the presence of potassium hydroxide as a catalyst in ethanol
CH
3
CH
CH
3
3
H C
3
CHO
H C
3
H C
3
POCl3 / DMF
MeI
KOH / Ethanol
H
CO
3
CH
3
HO
CH
3
H
CO
3
CH
3
3
1
2
O
R
MeOH/Aq.NaOH
OCH
3
CH3
CH
CH
3
3
CH
O
3
H C
3
Thiourea
H C
3
R
NH
KOH / C
H OH
5
2
H
CO
3
CH
3
R
N
H
S
4
5
Scheme 1

ONE-POT SYNTHESIS OF PYRIMIDINOTHIAZOLIDINONES
503
Table I Characterization data of 3-(2,3,6-trimethyl-4-methoxyphenyl)-1-methyl/aryl-2-propen-1-ones 4a–e and
4-(2,3,6-trimethyl-4-methoxyphenyl)-6-methyl/aryl-3,4-dihydropyrimidin-2-(1H)-thiones (5a–e)
Analysis (%) Found (Calculated)
Compd.
No.
Molecular Formulae
(Mol. Wt.)
Mp (◦C)
(Yield %)
R
C
H
N
4a
4b
4c
4d
4e
5a
5b
5c
5d
5e
CH3
Phenyl
4-Chloro phenyl
4-Tolyl
4-Nitro phenyl
CH3
Phenyl
4-Chloro phenyl
4-Tolyl
C14H18O2 (218)
64–66 (44) 77.17 (77.06) 8.21 (8.25)
98–100 (70) 81.59 (81.42) 7.51 (7.14)
126–128 (65) 72.41 (72.61) 7.22 (7.32)
102–104 (67) 81.82 (81.63) 7.73 (7.48)
114–116 (64) 70.33 (70.15) 6.98 (5.84)
—
—
—
C
C
C
C
19H20O2 (280)
19H19ClO2 (314)
20H22O2 (294)
19H19NO4 (325)
—
4.33 (4.30)
C15H20N2OS (276)
180–182 (72) 65.28 (65.21) 7.20 (7.24) 10.17 (10.14)
196–198 (71) 71.19 (71.00) 6.44 (6.50)
C
C
C
C
20H22N2OS (338)
20H21ClN2OS (372) 202–204 (62) 64.36 (64.42) 5.61 (5.63)
21H24N2OS (352) 128–130 (66) 71.68 (71.59) 6.83 (6.81)
8.26 (8.28)
7.55 (7.51)
7.91 (7.95)
4-Nitro phenyl
20H21N3O3S (383) 144–148 (67) 62.59 (62.66) 5.50 (5.48) 10.93 (10.96)
medium gave 4-(2,3,6-trimethyl-4-methoxyphenyl)-6-methyl/aryl-3,4-dihydropyrimidin-
2-(1H)-thiones 5. These pyrimidin-2-thiones 5 were further used for the synthesis of
N-bridged heterocycles. From the previous study,13 it is clear that the preparation of pyrim-
idinothiazolinones starting from pyrimidine-2-thiones involves two steps. In the first step,
pyrimidine-2-thione was condensed with monochloroacetic acid in the presence of anhy-
drous sodium acetate, and then in the next step it was converted into arylidene derivatives
by condensing with aromatic aldehydes in the presence of piperidine. However in the
present investigation, it was contemplated to carry out the synthesis of the title com-
pounds 2-substituted-5-(2,3,6-trimethyl-4-methoxyphenyl)-7-methyl/aryl-5H-pyrimidino-
[2,3-b]thiazolidine-3-ones 6 and 7 by one-pot synthesis in good yields by refluxing 4-
(2,3,6-trimethyl-4-methoxyphenyl)-6-methyl/aryl-3,4-dihydropyrimidin-2-(1H)-thiones 5,
monochloro acetic acid, and anhydrous sodium acetate with the corresponding aldehyde/5-
nitro-2-thiophenaldiacetate in acetic acid/acetic anhydride medium (Table II and Scheme
2). The structures of these compounds were established on the basis of elemental analysis,
IR, 1H NMR, and mass spectral studies.
Condensation of 2,3,6-trimethyl-4-methoxybenzaldehyde 3 with methyl ketones gave
3-(2,3,6-Trimethyl-4-methoxyphenyl)-1-methyl/aryl-2-propen-1-ones 4 (Table I). In a typ-
ical example of the 1H NMR spectrum of 4c, the three methyl protons came into resonance
as singlets at δ 2.16, 2.31, and 2.40 integrating for nine protons. The signal due to the
methoxy proton appeared as a singlet at δ 3.83. The olefinic protons appeared as two
doublets at δ 6.99 and 8.03 integrating for one proton each. The ortho- and meta-protons
of the 4-chlorophenyl group appeared as two doublets centered at δ 7.43 and 7.90 each
integrating for two protons. The other aromatic proton came into resonance as a singlet at
δ 6.62 integrating for one proton. Similarly the mass spectrum of 4c showed the molecular
ion peak at m/z 315 (M++1 peak)/317.
Reaction of chalcone 4 with thiourea in the presence of alcoholic potassium hydroxide
gave 4,6-disubstituted-3,4-dihydropyrimidin-2(1H)thiones 5. Characterization data of these
compounds 5 are given in Table I. In a typical example of the IR spectrum of 5a, the N H
stretching absorption was observed at 3200cm−1 and the C H stretching band was observed
1
at 2956 cm−1. The C S stretching absorption was seen at around 1174 cm−1. In the H
NMR spectrum of 5a, the four methyl groups came into resonance as four singlets at δ 1.77,
2.17, 2.33, and 2.40 integrating to 12 protons. The methoxy proton appeared as a singlet

504
B. LINGAPPA ET AL.
Table II Characterization data of 2-arylidine-5-(2,3,6-trimethyl-4-methoxyphenyl)-7-methyl/aryl-5H-
pyrimidino-[2,3-b]thiazolidine-3-ones 6a–j and 2-(5-nitro-2-thienylidine)-5-(2,3,6-trimethyl-4-methoxyphenyl)-
7-methyl/aryl-5H-pyrimidino-[2,3-b]thiazolidine-3-ones (7a–e)
Molecular
Formulae
(Mol. Wt.)
Analysis (%) Found (Calculated)
Comp.
No.
Mp (◦C)
(Yield%)
R
R1
4-Chloro
4-Methyl
4-Nitro
C
H
N
6
CH3
C24H23N2 ClO2S 195–198 (71) 65.68 (65.75) 5.21 (5.25)
6.43 (6.39)
6.65 (6.69)
9.32 (9.35)
7.97 (7.95)
5.81 (5.83)
5.25 (5.23)
5.48 (5.44)
7.75 (7.70)
6.71 (6.74)
4.88 (4.86)
9.26 (9.23)
8.14 (8.12)
7.64 (7.61)
7.55 (7.50)
(438)
C25H26N2O2S
(418)
C24H23N3O4S
(449)
6b
6c
6d
6e
6f
CH3
CH3
CH3
CH3
4-Cl
Phenyl
4-Cl
Phenyl
4-Cl
Phenyl
4-Cl
Phenyl
4-Cl
Phenyl
179–181 (69) 71.81 (71.77) 6.25 (6.22)
156–158 (69) 64.21 (64.14) 5.15 (5.12)
212–214 (62) 54.49 (54.54) 4.18 (4.16)
2-Bromo-6- C24H22BrN3O4S
Nitro
4-Phenyl
(527)
C30H28N2O2S
(480)
198–200 (64) 75.11 (75)
5.85 (5.83)
4-Chloro
4-Methyl
4-Nitro
C29H24N2Cl2O2S 163–165 (73) 64.95 (65.04) 4.50 (4.48)
(535)
C30H27N2ClO2S
(514)
C29H24N3ClO4S
(545)
6g
6h
6i
180–182 (71) 70.14 (70.03) 5.22 (5.25)
175–177 (63) 63.75 (63.85) 4.43 (4.40)
2-Bromo-6- C29H23N3ClBrO4S 202–204 (62) 55.91 (55.85) 3.82 (3.85)
Nitro
4-Phenyl
(623)
C35H29N2ClO2S
(576)
C22H21N3O4S2
(455)
C27H23N3O4S2
(517)
6j
128–130 (64) 72.85 (72.91) 5.05 (5.03)
120–124 (71) 58.11 (58.02) 4.59 (4.61)
161–163 (63) 62.72 (62.66) 4.51 (4.48)
7a
7b
7c
7d
7e
CH3
—
—
—
—
—
Phenyl
4-Cl
phenyl
4-Tolyl
C27H22ClN3O4S2 196–198 (62) 58.91 (58.80) 3.97 (3.99)
(551)
C28H25N3O4S2
(531)
C27H22N4O6S2
(562)
215–217 (65) 64.29 (64.34) 5.61 (5.63)
221–224 (61) 59.68 (59.79) 3.94 (3.91) 10.01 (9.96)
4-Nitro
phenyl
at δ 3.83 integrating to three protons. The methine proton appeared as a doublet at δ 4.56,
the pyrimidine-5H proton appeared as a doublet at δ 5.57, and the lone aromatic proton
appeared as a singlet at δ 6.55. Further evidence in support of the proposed structure was
obtained from the mass spectrum. It showed the molecular ion peak at m/z 276 in agreement
with the proposed molecular formula C15H20N2OS.
The one-pot three-component reaction of 4-(2,3,6-trimethyl-4-methoxyphenyl)-6-
methyl/aryl-3,4-dihydropyrimidin-2-(1H)-thiones 5, with the appropriate aldehyde and
monochloroacetic acid in acetic anhydride medium in the presence of sodium acetate
as a catalyst, gave a novel series of 2-arylidene-5-(2,3,6-trimethyl-4-methoxyphenyl)-7-
methyl/aryl-5H-pyrimidino-[2,3-b]thiazolidine-3-ones 6.
In the IR spectrum of 6a, the carbonyl absorption band of the thiazolidinone was
observed at 1653 cm−1 and the C N absorption band was seen at 1581 cm−1. In the
1H NMR spectrum of 6a, the pyrimidinyl methyl group appeared as a singlet at δ 1.96
integrating to three protons. The methyl groups appeared as three singlets at δ 2.09, 2.19,

ONE-POT SYNTHESIS OF PYRIMIDINOTHIAZOLIDINONES
505
OCH
3
CH
3
H
C
R
CH
3
3
ClCH2CO2
H
ClCH2CO2
H
CHO
AC2O/CH3CO2Na
AC2O/CH3CO2Na
NH
O
N
CH(OAC)
2
2
S
N
H
S
R1
OCH3
OCH3
CH3
CH3
5 a-e
CH3
O
CH3
O
H3C
H3C
N
N
S
S
R
N
R1
R
N
S
6 a-j
7 a-e
O
2N
Scheme 2
and 2.56 integrating to nine protons. The methoxy protons came into resonance as a singlet
at δ 3.81 integrating to three protons. The signal due to the methine proton appeared as a
doublet at δ 5.06 integrating to one proton, while the pyrimidine C5 H proton came into
resonance at δ 6.22 as a doublet integrating to one proton. The exo-cyclic vinylic protons
appeared as a singlet at δ 6.60 integrating to one proton. The signal due to other aromatic
protons merged together and appeared as multiplets in the region of δ 7.38–7.56 integrating
to five protons. Further the mass spectra of compound 6a showed the molecular ion peak
at m/z 439 (M++1 peak)/441.
A summary of the biological testing is provided in the Supplemental Materials
(available online).
CONCLUSION
This article reports the successful synthesis and pharmacological studies of the title
compounds via multicomponent reactions (MCR) in good yields. The anti-inflammatory
activity study revealed that the tested compounds showed moderate to good activity. The
antimicrobial activity study revealed that the compounds 6a, 6b, 6d, and 6j showed good
antibacterial and antifungal activity comparable with that of the standard drug.
EXPERIMENTAL
The melting points of the newly synthesized compounds were determined in open
capillary tubes and are uncorrected. IR spectra (cm−1) were recorded on a Perkin Elmer 577
1
spectrophotometer using KBr pellets. H NMR spectra were recorded on a Perkin Elmer
(Model RB-12) spectrometer (300 MHz) using CDCl3 or DMSO-d6 as solvent and TMS as
an internal standard. All chemical shift values are reported in δ scale downfield from TMS,
and proton signals are indicated as s = singlet, d = doublet, t = triplet, m = multiplet. Mass
spectrum was recorded on LC/MS (API 3000, Applied Biosystems) operating at 70 eV. C,

506
B. LINGAPPA ET AL.
H, N analysis was carried out on a Vairo-EL (Elementa) model. Purity of the compounds
was checked by TLC.
1-Methoxy-2,3,5-trimethylbenzene 2, 2,3,6-trimethyl-4-methoxybenzaldehyde 3,
and 4-(2,3,6-trimethyl-4-methoxyphenyl)-3-butene-2-one 4a were prepared as described
in the literature.12
Procedure for the Preparation of 1-Aryl-3-(2,3,6-trimethyl-4-
methoxyphenyl)-2-propene-1-ones 4b–e
A mixture of 2,3,6-trimethyl-p-methoxybenzaldehyde 3 (13.0 g, 0.07 mol) and sub-
stituted acetophenones (0.07 mol) in methanol (100 mL) were taken in a 250 mL RB flask.
The reaction mixture was cooled to 0–5◦C. Then 20% aqueous sodium hydroxide (35 mL)
was added with stirring by maintaining the temperature at 0–5◦C for about 30 min. The
mixture was stirred overnight at room temperature. The solid formed was filtered, washed
with water, and dried. It was further purified by recrystallization from ethyl acetate to give
1-aryl-3-(2,3,6-trimethyl-4-methoxyphenyl)-2-propen-1-ones 4b–e.
Procedure for the Preparation of 4-(2,3,6-Trimethyl-4-
methoxyphenyl)-6-methyl/aryl-3,4-dihydropyrimidin-2-(1H)-thiones 5a–e
A mixture of chalcone 4 (0.10 mol), thiourea (7.6 g, 0.10 mol), and potassium hydrox-
ide 11.2 g (0.2 mol) in ethanol (200 mL) was heated under reflux for 6–7 h. The reaction
was monitored by TLC. After the completion, the reaction volume was concentrated to half
and then poured into ice cold water and acidified with acetic acid. The solid that separated
was filtered, washed with water, and dried. It was further purified by recrystallization from
ethyl acetate. The characterization data of these compounds are given in Table I.
4-(2,3,6-Trimethyl-4-methoxyphenyl)-6-(4-chorophenyl)-3,4-
dihydropyrimidin-2-(1H)-thione 5c
1H NMR (CDCl3): δ 2.15 (s, 3H, CH3), 2.34 (s, 3H, CH3), 2.42 (s, 3H, CH3),
3.82 (S, 3H, OCH3), 5.06 (d, 1H, J = 4.6 Hz, methine-H), 5.94 (d, 1H, J = 4.6 Hz,
pyrimidine C5 H), 6.57 (s, 1H, C5 H of 2,3,6-trimethyl-4-methoxyphenyl), 6.75 (d, 2H,
J = 8.65 Hz, ortho protons of 4-chlorophenyl), 7.79 (d, 2H, J = 8.65 Hz, meta-protons
of 4-chlorophenyl), 7.81 (bs, 1H, N–H) and 7.92 (bs, 1H, NH); 13C NMR; 175.45 (C S),
157.14 (C-Cl), 135.32, 133.02, 131.84, 129.26, 128.40, 126.33 (aryl carbons), 100.91
(OCH3), 55.49 and 53.06 (C N), 20.98, 16.21 and 11.83 (CH3); Mass: (M++1) peak at
m/z 373 (56%) (M. F. C20H21N2ClOS). The chlorine isotope peak was observed at m/z 375
(18%).
General Procedure for the Preparation of 2-Substituted-5-(2,3,6-
trimethyl-4-methoxyphenyl)-7-methyl/aryl-5H pyrimidino-[2,3-b]
thiazolidine-3-ones 6a–j and 7a–e
A mixture of pyrimidino-2-(1H)-thione 5 (0.01 mol), monochloroacetic acid (1.41 g,
0.015 mol), anhydrous sodium acetate (2.0 g), glacial acetic acid (20 mL), acetic anhydride
(15 mL), and arylaldehyde/5-nitro-2-thiophenaldiacetate (0.01 mol) was heated under reflux
for 4 h. The reaction mixture was cooled and poured into crushed ice with vigorous stirring.

ONE-POT SYNTHESIS OF PYRIMIDINOTHIAZOLIDINONES
507
The contents were kept aside overnight. The separated solid was filtered, washed with
water, and recrystallized from a mixture of ethyl acetate and hexane to give compounds
6a–j and 7a–e. The characterization data of these compounds are given in Table II.
2-(4-Nitrobenzylidine)-5-(2,3,6-trimethyl-4-methoxyphenyl)-7-methyl-
1
5H-pyrimidino-[2,3-b]thiazolidine-3-one 6c. H NMR (CDCl3): δ 2.08 (s, 3H,
pyrimidinyl CH3) δ 2.11 (s, 3H, CH3), 2.21 (s, 3H, CH3), 2.58 (s, 3H, CH3), 3.82 (s, 3H,
OCH3), 5.69 (d, 1H, J = 4.4 Hz, methine- H), 6.44 (d, 1H, J = 4.4 Hz, pyrimidine C5 H),
6.51 (s, 1H, C5 H of 2,3,6-trimethyl-4-methoxyphenyl), 6.55 (s, 1H, exocyclic vinylic
and 7.64 (d, 2H, J = 8.80 Hz, ortho protons of 4-nitrophenyl) and 7.84 (d, 2H, J = 8.80
Hz, meta protons 4-nitrophenyl); Mass: (M.F: C24H23N3O4S). m/z 449 (48%)(M+); 13C
NMR; 163.45 (C O), 146.53 (C NO2), 140.15–12.78 (aryl carbons), 101.02 (OCH3),
55.49 and 53.06 (C N), 19.76, 17.32 and 14.27 (CH3).
2-(2-Bromo-6-nitrobenzylidine)-5-(2,3,6-trimethyl-4-methoxyphenyl)-7-
1
methyl-5H-pyrimidino-[2,3-b]thiazolidine-3-one 6d. H NMR (CDCl3): δ 2.07
(s, 3H, pyrimidinyl CH3) δ 2.13 (s, 3H, CH3), 2.21 (s, 3H, CH3), 2.55 (s, 3H, CH3),
3.84 (s, 3H, OCH3), 5.71 (d, 1H, J = 4.8 Hz, methine H), 6.49 (d, 1H, J = 4.8 Hz,
pyrimidine C5 H), 6.58 (s, 1H, C5 H of 2,3,6-trimethyl-4-methoxyphenyl), 6.65 (s, 1H,
exocyclic vinylic) and 7.64–8.34 (m, 3H, Ar-H); Mass: (M.F: C24H22N3O4BrS). m/z 528
(46%)(M++1). The bromine isotope peak was observed at m/z, 530 (42%).
2-(4-Phenylbenzylidine)-5-(2,3,6-trimethyl-4-methoxyphenyl)-7-methyl-
1
5H-pyrimidino-[2,3-b]thiazolidine-3-one 6e. H NMR (CDCl3): δ 1.96 (s, 3H,
pyrimidinyl CH3), δ 2.10 (s, 3H, CH3), 2.22 (s, 3H, CH3), 2.48 (s, 3H, CH3), 3.82 (s, 3H,
OCH3), 5.05 (d, 1H, J = 4.4 Hz, methine H), 6.31 (d, 1H, J = 4.4 Hz, pyrimidine C5 H),
6.56 (s, 1H, C5 H of 2,3,6-trimethyl-4-methoxyphenyl), 6.61 (s, 1H, exocyclic vinylic)
and 7.40–7.99 (m, 9H, Ar-H); Mass: (M.F: C30H28N2O2S). m/z 481 (38%)(M++1).
2-(2-Bromo-6-nitrobenzylidine)-5-(2,3,6-trimethyl-4-methoxyphenyl)-
1
7(4-chlorophenyl)-5H-thiozolo-[2,3-b]pyrimidin-3-one 6i. H NMR (CDCl3): δ,
2.16 (s, 3H, CH3), 2.24 (s, 3H, CH3), 2.63 (s, 3H, CH3), 3.84 (s, 3H, OCH3), 5.76 (d, 1H, J
= 4.8 Hz, methine H), 6.40 (d, 1H, J = 4.8 Hz, pyrimidine C5 H), 6.52 (s, 1H,exocyclic
vinylic), 6.63 (s, 1H, C5 H of 2,3,6-trimethyl-4-methoxyphenyl), and 7.34–7.98 (m, 7H,
Aryl-H); Mass: (M.F: C29H23N3O4BrClS). m/z 624 (48%)(M++1) and the cluster of
isotope peaks were observed at 625 (M++3), 627 (M++5) due to the presence of isotopes
of chlorine and bromine.
2-(5-Nitro-2-thienylidine)-5-(2,3,6-trimethyl-4-methoxyphenyl)-7-
1
methyl-5H-pyrimidino-[2,3-b]thiazolidine-3-one (7a). H NMR (CDCl3):
δ
1.97 (s, 3H, CH3 pyrimidinyl), δ 2.18 (s, 3H, CH3), 2.40 (s, 3H, CH3), 2.55 (s, 3H, CH3),
3.84 (s, 3H, OCH3), 5.11 (d, 1H, J = 4.7 Hz, methine H), 6.28 (d, 1H, J = 4.7 Hz,
pyrimidine C5 H), 6.63 (s, 1H, C5 H of 2,3,6-trimethyl-4-methoxyphenyl), 7.19 (d, 1H,
J = 8.36 Hz, thiophene-3H), 7.76 (s, 1H, exocyclic vinylic) and 7.93 (d, 1H, J = 8.36 Hz,
thiophene-4H); Mass: (M.F: C22H21N3O4S2). m/z 456 (36%)(M++1).
2-(5-Nitro-2-thienylidine)-5-(2,3,6-trimethyl-4-methoxyphenyl)-7-(p-
1
chlorophenyl)-5H-pyrimidino-[2,3-b]thiazolidine-3-one (7c). H NMR (DMSO-
d6): δ 2.21 (s, 3H, CH3), 2.36 (s, 3H, CH3), 2.46 (s, 3H, CH3), 2.55 (s, 3H, CH3), 3.91 (s,
3H, OCH3), 5.23 (d, 1H, J = 4.8 Hz, methine H), 6.31 (d, 1H, J = 4.8 Hz, pyrimidine
C5 H), 6.72 (s, 1H, C5 H of 2,3,6-trimethyl-4-methoxyphenyl), 6.91 (d, 2H, J = 8.68
Hz, ortho protons of p-chlorophenyl), 7.24 (d, 1H, J = 8.36 Hz, thiophene-3H), 7.79 (s, 1H,
exocyclic vinylic) and 7.89 (d, 2H, J = 8.68 Hz, meta protons of 4-chlorophenyl), 8.10 (d,
1H, J = 8.36 Hz, thiophene-4H); Mass: (M.F: C27H22ClN3O4S2). m/z 552 (41%)(M++1)

508
B. LINGAPPA ET AL.
and 554 (14%)(M++3). 13C NMR: 165.94 (C O), 150.53 (C-Cl), 138.34–128.64 (aryl
carbons), 101.22 (OCH3), 59.11 and 56.86 (C N), 20.98, 16.21 and 11.83 (CH3).
2-(5-Nitro-2-thienylidine)-5-(2,3,6-trimethyl-4-methoxyphenyl)-7-(p-
1
tolyl)-5H-pyrimidino-[2,3-b]thiazolidine-3-one (7d). H NMR (CDCl3): δ 2.13 (s,
3H, CH3), 2.24 (s, 3H, CH3), 2.38 (s, 3H, CH3), 2.56 (s, 3H, CH3), 3.81 (s, 3H, OCH3),
5.08 (d, 1H, J = 4.6 Hz, methine H), 6.31 (d, 1H, J = 4.6 Hz, pyrimidine C5 H), 6.58
(s, 1H, C5 H of 2,3,6-trimethyl-4-methoxyphenyl), 6.93 (d, 2H, J = 8.64 Hz, ortho
protons of 4-tolyl), 7.11 (d, 1H, J = 8.36 Hz, thiophene-3H), 7.41 (d, 2H, J = 8.64 Hz,
meta protons of 4-tolyl), 7.79 (s, 1H, exocyclic vinylic) and 7.91 (d, 1H, J = 8.36 Hz,
thiophene-4H); Mass: (M.F: C28H25N3O4S2). m/z 532 (38%)(M++1).
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