synthesis of a new series of thiazolyl- methyl(carbonyl ... - farmacia

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SYNTHESIS OF A NEW SERIES OF THIAZOLYL-
METHYL(CARBONYL-METHYL)-OXI-
BENZALDEHYDE DERIVATIVES
CRISTINA MOLDOVAN 1* , OVIDIU ONIGA 1 , BRÎNDUŞA TIPERCIUC 1 ,
PHILLIPPE VERITE 2 , ADRIAN PÎRNĂU 3 , MARIUS BOJIŢĂ 1
1 “Iuliu Haţieganu” University of Medicine and Pharmacy, Faculty of
Pharmacy, 12 Ion Creangă Street, RO-400010 Cluj Napoca, Romania
2 University of Medicine and Pharmacy Rouen, Faculty of Pharmacy,
Department of Analytical Chemistry, 22 Boulevard Gambetta, F-76183
Rouen Cedex, France
3 National Institute for Research and Development of Isotopic and
Molecular Technologies, RO-400293 Cluj Napoca, Romania
*corresponding author: cris.moldovan@yahoo.com
Abstract
A new series of thiazolyl-methyl (carbonyl-methyl)-oxi-benzaldehydes (5, 8-12)
was prepared by the reaction between a series of 2-aryl-thiazoles and o, m or p-OH
benzaldehyde. The obtained aldehydes were used as key intermediates for the synthesis of
2-thioxo-1,3-thiazolidin-4-one derivatives (13-16) and of pyrimidine-2,4,6-trione
derivatives (17-19). The structures of the newly synthesized compounds were confirmed by
TLC, elemental analysis and spectroscopic (MS, IR, 1 H NMR) data.
Rezumat
Au fost obţinute noi serii de tiazolil-metil(carbonil-metil)-oxi-benzaldehide (5, 8-12)
prin reacţia dintre o serie de 2-aril-tiazoli şi o, m sau p-OH benzaldehidă. Aldehidele obţinute au
fost utilizate ca intermediari cheie în sinteza unor derivaţi de 2-tioxo-1,3-tiazolidin-4-onă (13-
16) şi de pirimidin-2,4,6-trionă (17-19). Structurile noilor compuşi sintetizaţi au fost confirmate
prin CSS, analiză elementală şi spectroscopie (SM, IR, 1 H RMN).
Keywords: 2-Aryl-thiazoles; 2-thioxo-1,3-thiazolidin-4-one derivatives;
pyrimidine-2,4,6-trione derivatives
Introduction
Bacteria have been the cause of some of the most deadly diseases
and widespread epidemics in human civilization. The treatment of infectious
diseases still remains an important and challenging problem due to the
combination of factors, including emerging infectious diseases and the
increasing number of multi-drug resistant microbial pathogens. In spite of a
large number of antibiotics and chemotherapeutics available today, due to
the widespread use and misuse of antibiotics, bacterial resistance has
become a serious public health problem, always demanding new classes of
antibacterial agents. A potential approach to overcome the resistance

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problem may be represented by the design of innovative agents having a
different mechanism of action, so that it can’t occur any cross-resistance
with the therapeutic agents in use.
In the family of heterocyclic compounds, nitrogen-containing
heterocycles with a sulfur atom represent an important class of compounds
in the medicinal chemistry. Thiazoles and their derivatives have attracted
continuing interest over the decades because of their varied biological
activities: antibacterial [1-3], antiviral [4], antifungal [5], treatment of
allergies, pain, hypertension, inflammation, schizophrenia, HIV infections,
hypnotics, fibrinogen receptor antagonists with antithrombotic activity [6].
Apart from these, thiazolidin-4-ones show an antitumor [7,8],
antituberculosis, anticonvulsant [9] activity. Data from literature report that
the entrance of arylidene moieties at different positions of the 1,3-
thiazolidine ring enhanced the antimicrobial activity [10,11].
Pyrimidine 2,4,6–trione derivatives exert important action on the
central nervous system, and recently have been found totally new biomedicinal
applications in fields such as cancer (possess a marked inhibitory activity
against the matrix metalloproteinases and showed antimetastatic and antitumor
activity [12]) and AIDS therapy, and protease inhibitors [13].
As part of our ongoing studies in developing new active
antimicrobials [14-20], we report the synthesis of 3 new series of
structurally novel 2-aryl-thiazoles, various substituted in the 4 or 5 position
with different voluminous fragments incorporating 2-thioxo-1,3-
thiazolidine-4-one or pyrimidine 2,4,6–trione moieties.
Materials and methods
General Procedures. All reagents and solvents were obtained
from commercial sources. According to literature protocols there were
prepared: 4-methyl-2-phenyl-5-bromoacetyl-thiazole [21] and 2-aryl-4-
iodomethyl-thiazole [22]. Analytical thin layer chromatography (TLC) was
carried out on precoated Silica Gel 60F 254 sheets using UV absorption for
visualization. The melting points were taken with two melting point meters,
Electrothermal and MPM-H1 Schorpp and were uncorrected. FT-IR spectra
were recorded on a Nicolet 210 FT-IR spectrometer with a MCT detector
and an Omnic 4.1b soft system, using potassium bromide. The 1 HNMR
spectra were recorded at room temperature on a Bruker Avance NMR
spectrometer operating at 500 MHz. Chemical shift values were reported
relative to tetramethylsilane (TMS) as internal standard. The samples were
prepared by dissolving the synthesized powder of the compounds in DMSOd6
(δ H = 2.51ppm) as solvent and the spectra were recorded using a single

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excitation pulse of 12 µs. GC-MS analyses were performed with an Agilent
gas chromatograph 6890 equipped with an apolar Macherey Nagel
Permabond SE 52 capillary column. Elemental analysis was registered with
a Vario El CHNS instrument.
4-[2-(4-Methyl-2-phenyl-thiazole-5-yl)-2-oxo-ethoxy]-benzaldehyde (5).
To a mixture of p-OH-benzaldehyde (0.488 g, 4 mmol) and K 2 CO 3 anhydrous
(1.65 g, 12 mmol) in dry acetone (20mL) was added the 4-methyl-2-phenyl-5-
bromoacetyl-thiazole 4 (1.18 g, 4 mmol). The mixture was heated on a water
bath, in anhydrous conditions, for 5 h. The reaction mixture was afterwards
poured on water with ice. The precipitate was filtered off and washed with
water (50 mL) to obtain the aldehyde 5 (0.852 g, 63.2%). Brown solid. Mp =
132-135 o C. 1 H NMR (500 MHz, DMSO-d6): δ ppm = 2.7 (s, 3H, CH 3 ), 5.4 (s,
2H, CH 2 ), 7.1 (d, 2H, 2H a’ -arom), 7.53-7.64 (m, 3H, 2H a -arom, H-paraC 6 H 5 -
), 8.00 (d, 2H, 2H b -arom), 8.2 (d, 2H, H b’ -arom), 10 (s, 1H, CHO). IR (KBr):
ν= 3060 (CH arom ), 2918 and 2850 (CH aliph ), 1698 (C=O), 1652 (C=O, CHO),
1643 (C=N), 1590 (C=C) cm -1 . Anal.Calcd.(%) for C 19 H 15 NO 3 S (Molec.
Mass: 337.39, Exact Mass: 337.077): C67.64, H4.48, N4.15, S9.5. Found:
C67.45, H4.47, N4.14, S9.53. MS (EI, 70eV): m/z (%) 337 (28), 202 (100),
174 (15), 121 (5), 104 (5), 71 (12).
2-[2-(4-Bromo-phenyl)-thiazol-4-ylmethoxy]-benzaldehyde (8). To a
mixture of o-OH-benzaldehyde (0.366 g, 3 mmol) and K 2 CO 3 anhydrous
(1.242 g, 9 mmol) in dry acetone (15 mL) was added the 2-(4-Bromophenyl)-4-iodomethyl-thiazole
6 (1.13 g, 3 mmol). The mixture was heated
on a water bath, in anhydrous conditions, for 3 h. The reaction mixture was
afterwards cooled; the precipitate was filtered off to obtain the aldehyde 8
(0.87g, 77.54%). White solid. Mp = 148-150 o C. 1 H NMR (500 MHz,
DMSO-d6): δ ppm = 5.3 (s, 2H, CH 2 ), 7.1 (t, 1H, H-paraC 6 H 5 -), 7.26 (d, 1H,
H a ’-arom), 7.38 (d, 2H, H b -arom), 7.51 (t, 1H, H b’ -arom), 7.6 (s, 1H,
Hthiazole ), 7.85 (d, 2H, H a -arom), 7.9 (d, 1H, H a’’ -arom), 10.45 (s, 1H,
CHO). IR (KBr): ν= 3063 (CH arom ), 2919 (CH aliph ), 1670 (C=O, CHO),
1640 (C=N), 1593 (C=C), 1071 (C-Br) cm -1 . Anal.Calcd.(%) for
C 17 H 12 BrNO 2 S (Molec. Mass: 374.25, Exact Mass: 372.977): C54.56,
H3.23, N3.74, S8.57. Found: C54.44, H3.2, N3.73, S8.59. MS (EI, 70 eV):
m/z (%) 375 (9), 373 (9), 252 (100), 254 (100), 182 (9), 180 (9), 71 (38).
3-[2-(4-Bromo-phenyl)-thiazol-4-ylmethoxy]-benzaldehyde (9). To a
mixture of m-OH-benzaldehyde (0.366 g, 3 mmol) and K 2 CO 3 anhydrous
(1.242 g, 9 mmol) in dry acetone (15 mL) was added the 2-(4-Bromophenyl)-4-iodomethyl-thiazole
6 (1.14 g, 3 mmol). The mixture was heated
on a water bath, in anhydrous conditions, for 3 h. The reaction mixture was
afterwards cooled; the precipitate was filtered off to obtain the aldehyde 9

FARMACIA, 2009, Vol. 57, 4 455
(0.922g, 82.17%). Yellow solid. Mp = 135-137 o C. 1 H NMR (500 MHz,
DMSO-d6): δ ppm = 5.1 (s, 2H, CH 2 ), 6.657 (d, 1H, H a’’ -arom), 6.78 (d, 1H,
H’-paraC 6 H 5 -), 7.105 (t, 1H, H b’ -arom), 7.624 (s, 1H, H a’ -arom ), 7.798 (s,
1H, Hthiazole), 7.871 (d, 2H, 2H b -arom), 7.92 (d, 2H, 2H a -arom), 10.2 (s,
1H, CHO). IR (KBr): ν= 3061 (CH arom ), 2926 (CH aliph ), 1698 (C=O, CHO),
1638 (C=N), 1600 (C=C), 1070 (C-Br) cm -1 . Anal.Calcd.(%) for
C 17 H 12 BrNO 2 S (Molec. Mass: 374.25, Exact Mass: 372.97): C54.56, H3.23,
N3.74, S8.57. Found: C54.39, H3.215, N3.73, S8.54. MS (EI, 70 eV): m/z
(%) 375 (9), 373 (9), 252 (100), 254 (100), 182 (9), 180 (9), 71 (38).
4-[2-(4-Bromo-phenyl)-thiazol-4-ylmethoxy]-benzaldehyde (10). To a
mixture of p-OH-benzaldehyde (0.366 g, 3 mmol) and K 2 CO 3 anhydrous
(1.242 g, 9 mmol) in dry acetone (15 mL) was added the 2-(4-Bromophenyl)-4-iodomethyl-thiazole
6 (1.13 g, 3 mmol). The mixture was heated
on a water bath, in anhydrous conditions, for 3 h. The reaction mixture was
afterwards cooled; the precipitate was filtered off to obtain the aldehyde 10
(0.91g, 81.10%). Brown solid. Mp = 137-139 o C. 1 H NMR (500 MHz,
DMSO-d6): δ ppm = 5.3 (s, 2H, CH 2 ), 7.272 (d, 2H, 2H a’ -arom), 7.52 (d, 2H,
2H b -arom), 7.61 (d, 2H, 2H a -arom), 7.834 (s, 1H, Hthiazole), 7.968 (d, 2H,
H b’ -arom), 10 (s, 1H, CHO). IR (KBr): ν= 3058 (CH arom ), 2921 (CH aliph ),
1697 (C=O, CHO), 1635 (C=N), 1589 (C=C), 1071 (C-Br) cm -1 .
Anal.Calcd.(%) for C 17 H 12 BrNO 2 S (Molec. Mass: 374.25, Exact Mass:
372.97): C54.56, H3.23, N3.74, S8.57. Found: C54.41, H3.22, N3.73,
S8.565. MS (EI, 70 eV): m/z (%) 375 (9), 373 (9), 252 (100), 254 (100),
182 (9), 180 (9), 71 (38).
3-(2-Phenyl-thiazol-4-ylmethoxy)-benzaldehyde (11). To a mixture of m-
OH-benzaldehyde (0.244 g, 2 mmol) and K 2 CO 3 anhydrous (0.828 g, 6
mmol) in dry acetone (10 mL) was added the 2-phenyl-4-iodomethylthiazole
7 (0.6 g, 2 mmol). The mixture was heated on a water bath, in
anhydrous conditions, for 3 h. The reaction mixture was afterwards cooled
and poured on water. The obtained precipitate was filtered off to obtain 11
(0.53 g, 71.23%). Yellow solid. Mp = 67-70 o C.
1 H NMR (500 MHz,
DMSO-d6): δ ppm = 5.25 (s, 2H, CH 2 ), 7.62 (s, 1H, H a’ -arom), 7.82 (s, 1H,
Hthiazole ), 7.96 (d, 2H, H b -arom), 10.00 (s, 1H, CHO). IR (KBr): ν= 3043
(CH arom ), 2922 (CH aliph ), 1682 (C=O, CHO), 1609 (C=N), 1593 (C=C) cm -1 .
Anal.Calcd.(%) for C 17 H 13 NO 2 S (Molec. Mass: 295.35, Exact Mass:
295.066): C69.13, H4.44, N4.74, S10.85. Found: C68.87, H4.43, N4.73,
S10.83. MS (EI, 70 eV): m/z (%) 295 (18), 174 (100), 121 (14), 71 (17).
4-(2-Phenyl-thiazol-4-ylmethoxy)-benzaldehyde (12). To a mixture of p-
OH-benzaldehyde (1.22 g, 10 mmol) and K 2 CO 3 anhydrous (4.14 g, 30
mmol) in dry acetone (50 mL) was added the 2-phenyl-4-iodomethyl-

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thiazole 7 (3 g, 10 mmol). The mixture was heated on a water bath, in
anhydrous conditions, for 5 h. The reaction mixture was afterwards cooled
and poured on water. The obtained precipitate was filtered off to obtain 12
(2.91g, 78.22%). White solid. Mp = 82-84 o C. 1 H NMR (500 MHz, DMSOd6):
δ ppm = 5.3 (s, 2H, CH 2 ), 7.1 (d, 2H, H a’ -arom), 7.51-7.52 (m, 3H, 2H a -
arom, H-paraC 6 H 5 -), 7.59 (d, 2H, H b’ -arom), 7.83 (s, 1H, Hthiazole), 10.00
(s, 1H, CHO). IR (KBr): ν= 3047 (CH arom ), 2922 (CH aliph ), 1682 (C=O,
CHO), 1615 (C=N), 1593 (C=C) cm -1 . Anal.Calcd.(%) for C 17 H 13 NO 2 S
(Molec. Mass: 295.35, Exact Mass: 295.066): C69.13, H4.44, N4.74,
S10.85. Found: C68.92, H4.43, N4.75, S10.812. MS (EI, 70 eV): m/z (%)
295 (18), 174 (100), 121 (14), 71 (17).
5-{4-[2-(4-Methyl-2-phenyl-thiazol-5-yl)-2-oxo-ethoxy]-benzylidene}-2-
thioxo-thiazolidin-4-one (13). To a mixture of 2-thioxo-1,3-thiazolidin-4-
one (0.133 g, 1 mmol) and anhydrous sodium acetate (0.246 g, 3 mmol) in
glacial acetic acid (5 mL) was added the compound 5 (0.337 g, 1 mmol).
The mixture was heated for 6 h, afterwards cooled and the obtained
precipitate was filtered off and washed with water (100mL) to obtain 13
(0.275 g, 60.84%). Yellow solid. Mp = 232-238 o C. 1 H NMR (500 MHz,
DMSO-d6): δ ppm = 2.77 (s, 3H, CH 3 ), 5.47 (s, 2H, CH 2 ), 7.18 (d, 2H, H a ’-
arom), 7.56 (s, 1H, CH), 7.57 (d, 2H, H b ’-arom), 7.59 (t, 1H, H-paraC 6 H 5 -),
7.82 (t, 2H, H a -arom), 8.04 (d, 2H, H b -arom) 13-14.5 (brs, 1H, NH). IR
(KBr): ν= 3432 (NH), 3058 (CH arom ), 2918 and 2851 (CH aliph ), 1692 (C=O),
1652 (C=O, -NHCO-), 1643 (C=N), 1589 (C=C), 1237 (C=S), 1054 (S-CS-
N), 641 (C-S) cm -1 . Anal.Calcd.(%) for C 22 H 16 N 2 O 3 S 3 (Molec. Mass:
452.56, Exact Mass: 452.032): C58.39, H3.56, N6.19, S21.25. Found:
C58.51, H3.567, N6.17, S21.18. MS (EI, 70eV): m/z (%) 452 (28), 202
(100), 188 (8), 174 (15), 133 (6), 121 (5), 104 (3), 71 (12).
5-{2-[2-(4-Bromo-phenyl)-thiazol-4-ylmethoxy]-benzylidene}-2-thioxothiazolidin-4-one
(14). To a mixture of 2-thioxo-1,3-thiazolidin-4-one
(0.133 g, 1 mmol) and anhydrous sodium acetate (0.246 g, 3 mmol) in
glacial acetic acid (5 mL) was added the compound 8 (0.374 g, 1 mmol).
The mixture was heated for 4 h, afterwards cooled. The obtained precipitate
was filtered off, washed with water (100 mL) and recrystallized from
ethanol, to obtain the compound 14 (0.32 g, 65.44%). Yellow solid. Mp =
271-273 o C. 1 H NMR (500 MHz, DMSO-d6): δ ppm = 5.4 (s, 2H, CH 2 ), 7.382
(d, 1H, H a’ -arom), 7.429 (d, 1H, H b’ -arom), 7.521 (t, 1H, H’-paraC 6 H 5 -),
7.703-7.733 (m, 2H, Hthiazole, H b’’ -arom), 7.868 (d, 2H, H b -arom), 7.912
(d, 2H, H b -arom), 7.944 (s, 1H, -CH=), 13.8 (brs, 1H, NH). IR (KBr): ν=
3446 (NH), 3043 (CH arom ), 2919 and 2849 (CH aliph ), 1698 (C=O), 1640
(C=N), 1593 (C=C), 1232 (C=S), 1070 (C-Br), 1051 (S-CS-N), 649 (C-S)

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cm -1 . Anal.Calcd.(%) for C 20 H 13 BrN 2 O 2 S 3 (Molec. Mass: 489.41, Exact
Mass: 487.932): C49.08, H2.68, N5.72, S19.65. Found: C49.24, H2.689,
N5.7, S19.59. MS (EI, 70eV): m/z (%) 489 (28), 487 (28), 254 (100), 252
(100), 182 (9), 180 (9), 133 (6), 71 (38).
5-[3-(2-Phenyl-thiazol-4-ylmethoxy)-benzylidene]-2-thioxo-thiazolidin-
4-one (15). To a mixture of 2-thioxo-1,3-thiazolidin-4-one (0.12 g, 0.9
mmol) and anhydrous sodium acetate (0.184 g, 2.25 mmol) in glacial acetic
acid (6 mL) was added the compound 11 (0.265 g, 0.9 mmol). The mixture
was heated for 4 h, afterwards cooled. The obtained precipitate was filtered
off, washed with water (100 mL) to obtain the compound 15 (0.25g,
67.75%). Yellow solid. Mp = 205-208 o C. 1 H NMR (500 MHz, DMSO-d6):
δ ppm = 5.3 (s, 2H, CH 2 ), 7.201-7.246 (m, 2H, H a’’ -arom, H’-paraC 6 H 5 -),
7.313 (s, 1H, CH), 7.483-7.533 (m, 4H, H b’ -arom, 2H a -arom, H-paraC 6 H 5 -
), 7.635 (s, 1H, H a’ -arom), 7.844 (s, 1H, Hthiazole), 7.968 (d, 2H, H b -
arom), 13.8-13.9 (brs, 1H, NH). IR (KBr): ν= 3430 (NH), 3060 (CH arom ),
2919 and 2850 (CH aliph ), 1699 (C=O), 1639 (C=N), 1589 (C=C), 1237
(C=S), 1050 (S-CS-N), 647 (C-S) cm -1 . Anal.Calcd.(%) for C 20 H 14 N 2 O 2 S 3
(Molec. Mass: 410.52, Exact Mass: 410.021): C58.52, H3.44, N6.82,
S23.43. Found: C58.7, H3.429, N6.8, S23.37. MS (EI, 70 eV): m/z (%) 410
(28), 174 (100), 133 (6), 104 (14), 71 (17).
5-[4-(2-Phenyl-thiazol-4-ylmethoxy)-benzylidene]-2-thioxo-thiazolidin-
4-one (16). To a mixture of 2-thioxo-1,3-thiazolidin-4-one (0.08 g, 0.6
mmol) and anhydrous sodium acetate (0.105 g, 1.5 mmol) in glacial acetic
acid (4 mL) was added the compound 12 (0.177 g, 0.6 mmol). The reaction
mixture was heated for 4 h, afterwards cooled; the obtained precipitate was
filtered off, to obtain the compound 16 (0.17g, 69.10%). Yellow solid. Mp =
223-5 o C. 1 H NMR (500 MHz, DMSO-d6): δ ppm = 5.32 (s, 2H, CH 2 ), 7.27
(d, 2H, H a’ -arom), 7.513-7.527 (m, 3H, 2H a -arom, H-paraC 6 H 5 -), 7.609 (d,
2H, H b’ -arom), 7.641 (s, 1H, -CH=), 7.851 (s, 1H, Hthiazole), 7.963 (d, 2H,
H b -arom), 13.7 (s, 1H, NH). IR (KBr): ν= 3432 (NH), 3059 (CH arom ), 2918
and 2851 (CH aliph ), 1698 (C=O), 1615 (C=N), 1590 (C=C), 1232 (C=S),
1051 (S-CS-N), 640 (C-S) cm -1 . Anal.Calcd.(%) for C 20 H 14 N 2 O 2 S 3 (Molec.
Mass: 410.52, Exact Mass: 410.021): C58.52, H3.44, N6.82, S23.43. Found:
C58.7, H3.448, N6.807, S23.35. MS (EI, 70 eV): m/z (%) 410 (28), 174
(100), 133 (6), 104 (14), 71 (17).
5-{4-[2-(4-Methyl-2-phenyl-thiazol-5-yl)-2-oxo-ethoxy]-benzylidene}-
pyrimidine-2,4,6-trione (17). To a mixture of pyrimidine-2,4,6-trione
(0.128 g, 1 mmol) and anhydrous sodium acetate (0.246 g, 3 mmol) in
glacial acetic acid (10 mL) was added the compound 5 (0.337 g, 1 mmol).
The mixture was heated for 6 h, afterwards cooled and the obtained

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precipitate was filtered off and washed with water (100mL) to obtain 17
(0.315g, 70.47%). Yellow solid. Mp = 269-271 o C. 1 H NMR (500 MHz,
DMSO-d6): δ ppm = 2.8 (s, 3H, CH 3 ), 5.51 (s, 2H, CH 2 ), 7.143 (d, 2H, 2H a ’-
arom), 7.54-7.61 (m, 3H, H a -arom, H-paraC 6 H 5 -), 8.054 (d, 2H, H b’ -arom),
8.264 (s, 1H, -CH=), 8.359 (d, 2H, H b -arom), 11.2 (s, 1H, NH), 11.32 (s,
1H, NH). IR (KBr): ν= 3431 (NH), 3063 (CH arom ), 2919 and 2851 (CH aliph ),
1731 (C=O, -NH-CO-NH-), 1672 (C=O), 1655 (C=O) cm -1 . Anal.Calcd.(%)
for C 23 H 17 N 3 O 5 S (Molec. Mass: 447.46, Exact Mass: 447.088): C61.74,
H3.83, N9.39, S7.16. Found: C61.53, H3.89, N9.37, S7.178. MS (EI,
70eV): m/z (%) 447 (6), 202 (100), 174 (15), 128 (9), 104 (8), 71 (15).
5-[3-(2-Phenyl-thiazol-4-ylmethoxy)-benzylidene]-pyrimidine-2,4,6-
trione (18). To a mixture of pyrimidine-2,4,6-trione (0.096 g, 0.75 mmol)
and anhydrous sodium acetate (0.184 g, 2.25 mmol) in glacial acetic acid (8
mL) was added the compound 11 (0.221 g, 0.75 mmol). The mixture was
heated for 4 h, afterwards cooled. The obtained precipitate was filtered off,
washed with water (100 mL) to obtain the compound 18 (0.21g, 69.3%).
Brown solid. Mp >300 o C. 1 H NMR (500 MHz, DMSO-d6): δ ppm = 5.1 (s,
2H, CH 2 ), 6.65-6.681 (m, 2H, H a’ -arom, H a’’ -arom), 6.774 (d, 1H, H’-
paraC 6 H 5 -), 7.091 (t, 1H, H b’ -arom), 7.502-7.515 (m, 3H, H a -arom,
Hthiazole), 7.759 (s, 1H, -CH=), 7.957 (t, 1H, H’-paraC 6 H 5 -), 7.97 (d, 2H,
H b -arom), 11.12 (s, 1H, NH), 11.42 (s, 1H, NH). IR (KBr): ν= 3432 (NH),
3063 (CH arom ), 2920 and 2852 (CH aliph ), 1732 (C=O, -NH-CO-NH-), 1672
(C=O), 1658 (C=O) cm -1 . Anal.Calcd.(%) for C 21 H 15 N 3 O 4 S (Molec. Mass:
405.42, Exact Mass: 405.078): C62.21, H3.73, N10.36, S7.91. Found:
C61.99, H3.74, N10.33, S7.89. MS (EI, 70eV): m/z (%) 405 (28), 174
(100), 128 (9), 104 (8), 71 (15).
5-[4-(2-Phenyl-thiazol-4-ylmethoxy)-benzylidene]-pyrimidine-2,4,6-trione
(19). To a mixture of pyrimidine-2,4,6-trione (0.064 g, 0.5 mmol) and
anhydrous sodium acetate (0.105 g, 1.5 mmol) in glacial acetic acid (4 mL)
was added the compound 12 (0.148 g, 0.5 mmol). The reaction mixture was
heated for 4 h, afterwards cooled; the obtained precipitate was filtered off, to
obtain the compound 19 (0.14g, 69.3%). Yellow solid. Mp = 270 o C. 1 H NMR
(500 MHz, DMSO-d6): δ ppm = 5.3 (s, 2H, CH 2 ), 7.13 (d, 2H, H a’ -arom), 7.5-
7.6 (m, 3H, H a -arom, H-paraC 6 H 5 -), 7.8 (s, 1H, Hthiazole), 8.00 (d, 2H, H b’ -
arom), 8.2 (s, 1H, -CH=), 8.41 (d, 2H, H b’ -arom), 11.15 (s, 1H, NH), 11.3 (s,
1H, NH). IR (KBr): ν= 3431 (NH), 3064 (CH arom ), 2918 and 2851 (CH aliph ),
1731 (C=O, -NH-CO-NH-), 1673 (C=O), 1656 (C=O) cm -1 . Anal.Calcd.(%)
for C 21 H 15 N 3 O 4 S (Molec. Mass: 405.42, Exact Mass: 405.078): C62.21,
H3.73, N10.36, S7.91. Found: C62.43, H3.74, N10.33, S7.93. MS (EI, 70eV):
m/z (%) 405 (28), 174 (100), 128 (9), 104 (8), 71 (15).

FARMACIA, 2009, Vol. 57, 4 459
Results and discussion
The synthetic strategies adopted to obtain the target compounds are
presented in Figures 1-3. The key intermediates noted as 5, 8-12 were
prepared in good yields by etherification of 2-phenyl-4-methyl-5-
bromoacetyl-thiazole 4, respectively 2-phenyl-4-iodomethyl-thiazole 7 and
his 4-bromoderivative 6 with o, m or p-hydroxybenzaldehyde 1, 2, 3, in
refluxing dry acetone, in the presence of anhydrous K 2 CO 3 (Figure 1).
Figure 1
Synthesis of some thiazolyl-carbonyl-methyl-oxi and
thiazolyl-methyl-oxi-benzaldehyde derivatives
The aldehydes 5, 8, 11 and 12 were allowed to condense with 2-
thioxo-1,3-thiazolidin-4-one, in refluxing glacial acetic acid in the presence
of anhydrous sodium acetate for 4-6 h to afford, in good yields, 5-
arylmethylene-2-thioxo-1,3-thiazolidin-4-one 13-16 (Figure 2).
In order to obtain, in good yields, new 5-arylmethylene-pyrimidine-
2,4,6-trione derivatives, the aldehydes 5, 11 and 12 were treated with
pyrimidine-2,4,6-trione, in the same conditions as mentioned previously
(Figure 3).
The structures of compounds 13-16 were confirmed by
microanalytical and spectral data. Thus, the 1 HNMR spectra showed signals
corresponding to methyl (compound 13), methylene, olefinic, aromatic and
NH protons. Further, the infrared spectra showed absorptions characteristic

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FARMACIA, 2009, Vol. 57, 4
for NH, C=O and C=S groups, in addition to other absorptions correlated to
the assigned structures. Also, MS showed correct molecular ion peaks
beside some of the abundant fragments.
The structures of compounds 17-19 were confirmed by
microanalytical and spectral data. Thus, the 1 HNMR spectra showed signals
corresponding to methyl (compound 17), methylene, olefinic, aromatic and
NH protons. Further, the infrared spectra showed absorptions characteristic
for NH, C=O groups, in addition to other absorptions correlated to the
assigned structures. Also, MS showed correct molecular ion peaks beside
some of the abundant fragments.
Figure 2
Condensation of 2-thioxo-1,3-thiazolidin-4-one with the thiazolyl-carbonyl-methyl-oxi and
thiazolyl-methyl-oxi-benzaldehyde derivatives
Figure 3
Condensation of pyrimidine 2, 4, 6-trione with the thiazolyl-carbonyl-methyl-oxi and
thiazolyl-methyl-oxi-benzaldehyde derivatives

FARMACIA, 2009, Vol. 57, 4 461
Conclusions
A number of 6 new thiazolyl-methyl (carbonyl-methyl)-oxibenzaldehydes,
4 new 5-arylmethylene-2-thioxo-1,3-thiazolidin-4-one
derivatives and 3 new 5-arylmethylene-pyrimidine-2,4,6-trione derivatives
was synthesized, as potential new therapeutical agents. Their structures were
confirmed by TLC, elemental analysis and spectroscopic (MS, IR, 1 H NMR)
data.
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Manuscript received: 02.03.2009