Reaction of N-(Per-O-acetyl-β-D-glucopyranosyl)-N′-(4',6'- diarylpyrimidine-2'-yl)thioureas with ethyl bromoacetate

Article abstract of DOI:10.1155/2011/348479

Some new 2-iminothiazolidin-4-ones having pyrimidine ring have been synthesized by reaction of substituted N-(per-O-acetyl-β-D-glucopyranosyl) -N′-(4',6'-diarylpyrimidine-2'-yl)thioureas with ethyl bromoacetate. The structure of isomeric products has been

Full text of DOI:10.1155/2011/348479

ISSN: 0973-4945; CODEN ECJHAO
E-Journal of Chemistry
2011, 8(3), 1355-1361
http://www.e-journals.net
Reaction of N-(Per-O-acetyl-β-D-glucopyranosyl)-N’-(4’,6’-
diarylpyrimidine-2’-yl)thioureas with Ethyl Bromoacetate
NGUYEN DINH THANH
Faculty of Chemistry, College of Science, Hanoi National University
19 Le Thanh Tong, Ha Noi-10000, Viet Nam
nguyendinhthanh@hus.edu.vn
Received 29 October 2010; Accepted 11 January 2011
Abstract: Some new 2-iminothiazolidin-4-ones having pyrimidine ring have
been synthesized by reaction of substituted N-(per-O-acetyl-β-D-glucopyranosyl)
-N’-(4’,6’-diarylpyrimidine-2’-yl)thioureas with ethyl bromoacetate. The
structure of isomeric products has been confirmed by spectroscopic methods,
such as IR, 1H and 13C NMR.
Keywords: Glucopyranosyl thiourea, Thiazolidin-4-one, Ethyl bromoacetate, 2-Iminothiazolidin-4-one
Introduction
Thiazolidin-4-one represents a prevalent scaffold in drug discovery. A survey of the most
recent literature indicate that chemicals containing this moiety are potential antibacterial,
antimycobacterial, anticonvulsant, antiparasitic, anti-inflammatory, analgesic and herbicidal
agents. Moreover, it has been reported that thioureas can serve as the precursor of
thiazolidin-4-one derivatives1. Interestingly, Garnaik et al.2 reported that several
2-(arylimino)-4-tetra-O-acetyl-β-D-glucopyranosyl-4-thiazolidinones showed promising
antimicrobial and antifungal activities. Thiazolidin-4-one could be obtained from cyclization
of substituted thiourea with chloroacetic acid (in the presence of weak base). Several reports
regarding the condensation of thiosemicarbazides with alkyl halides have pointed that main
products are of compound types3 resulting from cyclization at N-4. In the presence of a weak
base, Saleh et al.4 cyclized substituted thioureas with chloroacetic acid, giving thiazolidin-4-
one compounds substituted at N-4. Conversely, the cyclization at N-2 has been more
scarcely reported. Moghaddam and Hojabri5 and Rajanarendar et al.6 have reported
cyclizations at N-2 position. A detailed study of the condensation of thiosemicarbazides
with ethyl bromoacetate to give N-2 isomers as major products has been reported7. Yu
Xin Li et al8 have reported cyclizations at N-2 position in 1-alkoxy(phenyl)
thiophosphoryl-4-(per-O-acetylglycosyl)thiosemicarbazides to give 3-alkoxy(phenyl)-
thiophosphorylamido-2-(per-O-acetylglycosyl-1’-imino)thiazolidin-4-one and at N-4 position

Reaction of Substituted Thioureas with Ethyl Bromoacetate
1356
in 1-arylsulfonyl-4-(N-per-O-acetyl-
β
2-phenylsulfonylhydrazono-3-(per-O-acetyl-
-D-glycopyranosyl) thiosemicarbazides to afford
-D-glycopyranosyl) thiazolidin-4-ones.
β
Continuing our studies9 on the synthesis of peracetylated glycopyranosyl isothiocyanate
and conversion into corresponding thioureas containing pyrimidine ring, we report here the
synthesis and spectral characterization of some iminothiazolidin-4-one compounds from
N-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-N’-(4’,6’-diarylpyrimidine-2’-yl)thioureas.
Experimental
All the starting materials and reagents were purchased from commercial suppliers and used
after further purification. 2,3,4,6-Tetra-O-acetyl-
β
-D-glucopyranosyl isothiocyanate was
prepared by the reaction of per-O-acetylated-
β
-D-glucopyranosyl bromide (prepared from
D-glucose)10 with lead thiocyanate in dried toluene2 and N-(2,3,4,6-tetra-O-acetyl-β-D-
glucopyranosyl)-N’-(4’,6’-diarylpyrimidine-2’-yl)thioureas by our method9.
Physical measurements
Melting points were measured on STUART SMP3 (BIBBY STERILIN-UK). The FTIS-
spectra was recorded on Impact 410 FT-IR Spectrometer (Nicolet, USA) in form of KBr and
1
using reflex-measure method. The H NMR and 13C NMR spectra were recorded on an
Avance spectrometer AV500 (Bruker, Germany) at 500.13 MHz and 125.77 MHz,
respectively, using DMSO-d6 as solvent and TMS as an internal reference. MS spectra were
recorded on mass spectrometer LC-MS 1100 LC-MSD Trap-SL (Agilent technologies,
USA) in metanol. Analytical thin-layer chromatography (TLC) was performed on silica gel
60F254 No. 5715 (Merck, Germany) with EtOAc and light petroleum (bp 60-90 °C). The
spots were visualized by exposure to UV light or by spraying the plats with 10% (v/v)
H2SO4 in EtOH, followed by heating.
General synthetic method of (Z)-3-(2’,3’,4’,6’-tetra-O-acetyl-
(4”,6”-diphenylpyrimidin-2”-ylimino)-thiazolidin-4-ones (2a-g) and (Z)-2-(2’,3’,4’,6’-
tetra-O-acetyl- -D-glucopyranosyl-1’-imino)-3-(4”,6”-diphenylpyrimidin-2”-yl)-
β-D-glucopyranosyl)-2-
β
thiazolidin-4-ones (2’a-g)
To a solution of thioureas 1 (5 mmol) in CHCl3 (20 mL), ethyl bromoacetate (1.0 g, 0.2 mL,
6 mmol) was added drop wise with stirring. The mixture was heated at reflux for 8-10 h and
the solvent was removed under diminished pressure until the volume was 10 mL and ethanol
(20 mL) was added and left overnight. A white separated crude product was filtered and
purified by recrystallization from toluene: ethanol (1:1) to afford the title isomeric
compounds 2 and 2’.
Compounds 2a/2’a: Yield 59%; mp. 180–185 ºC, ratio of 2a/2’a isomers 7.7/2.3; IR
(KBr, cm–1): ν 1752, 1740, 1591, 1577, 1567, 1513, 1237, 1032; (2a): 1H NMR (DMSO-
d6): δ 8.50–8.41 (m, 4H, H-2”’, H-6”’, H-2””, H-6””), 8.40 (s, 1H, H-5”), 7.46–7.42 (m, 3H,
H-3””, H-4””, H-5””), 7.27–7.13 (m, 2H, H-3”’, H-5”’), 6.38 (d, 1H, J 9.5 Hz, H-1’), 5.92
(t, 1H, J 9.5 Hz, H-2’), 5.64 (t, 1H, 9.5 Hz, H-3’), 5.01 (t, 1H, J 10.0 Hz, H-4’), 4.40–4.36
(m, 1H, H-5’), 4.18–4.12 (m, 2H, H-6’a, H-6’b), 4.16 (d, 1H, J 17.75 Hz, H-5a), 3.95 (d,
1H, J 17.75 Hz, H-5b), 2.04–1.91 (4×CH3CO); 13C NMR (DMSO-d6): δ 171.7 (C=O
lactam), 170.0–169.4 (4×COCH3), 165.5 (C-6”), 164.4 (C-1”), 163.3 (C-2”), 163.1 (C-2,
C=N), 163.0 (C-4”’), 136.1 (C-1””), 131.3 (C-1”’), 130.1 (d, J 8.80 Hz, C-2”’, C-6”’),
128.9 (C-4””), 128.8 (C-3””, C-5””), 128.2 (C-2””, C-6””), 115.9 (d, JCF 21.63 Hz, C-3”’,

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NGUYEN DINH THANH
C-5”’), 110.4 (C-5”), 80.3 (C-1’), 72.9 (C-5’), 72.2 (C-3’), 67.6 (C-2’), 67.5 (C-4’), 61.6 (C-
6’), 32.7 (C-5), 21.0–20.1 (4×COCH3). (2’a): 1H NMR (DMSO-d6): δ 8.50–8.41 (m, 4H, H-
2”’& H-6”’, H-2”” & H-6””), 8.40 (s, 1H, H-5”), 7.46–7.42 (m, 3H, H-3””, H-4””, H-5””),
7.27–7.13 (m, 2H, H-3”’, H-5”’), 6.47 (t, 1H, J 9.25 Hz, H-2’), 5.92 (t, 1H, J 9.5 Hz, H-1’),
5.54 (t, 1H, 9.5 Hz, H-3’), 5.19 (t, 1H, J 9.75 Hz, H-4’), 4.35–4.30 (m, 1H, H-5’), 4.18–4.12
(m, 2H, H-6’a, H-6’b), 4.16 (d, 1H, J 17.75 Hz, H-5a), 3.95 (d, 1H, J 17.75 Hz, H-5b), 2.04–
1.91 (4×CH3CO); 13C NMR (DMSO-d6): δ 171.7 (C=O lactam), 169.9–169.4 (4×COCH3),
165.5 (C-6”), 164.4 (C-1”), 163.3 (C-2”), 163.1 (C-2, C=N), 163.0 (C-4”’), 136.1 (C-1””),
131.3 (C-1”’), 130.1 (d, J 8.80 Hz, C-2”’, C-6”’), 128.9 (C-4””), 128.8 (C-3””, C-5””),
128.2 (C-2””, C-6””), 115.9 (d, JCF 21.63 Hz, C-3”’, C-5”’), 110.4 (C-5”), 80.0 (C-1’), 73.0
(C-5’), 72.2 (C-3’), 67.6 (C-2’), 67.4 (C-4’), 61.6 (C-6’), 32.7 (C-5), 21.0–20.1 (4×COCH3).
Compounds 2b/2’b: Yield 68%; mp. 190–193 ºC, ratio of 2b/2’b isomers 7.5/2.5; IR
(KBr, cm–1): ν 1752, 1740, 1591, 1577, 1567, 1513, 1237, 1032; (2b): 1H NMR (DMSO-d6):
δ 8.44 (s, 1H, H-5”), 8.40 (d, 2H, J 8.5 Hz, H-2”’, H-6”’), 8.44-8.39 (m, 2H, H-2””, H-6””),
7.84 (d, 2H, J 8.5 Hz, H-3”’, H-5”’), 7.65–7.64 (m, 3H, H-3””, H-4””, H-5””), 6.42 (d, 1H, J
9.0 Hz, H-1’), 5.97 (t, 1H, J 9.25 Hz, H-2’), 5.68 (t, 1H, 9.25 Hz, H-3’), 5.06 (t, 1H, J 10.0
Hz, H-4’), 4.43–4.41 (m, 1H, H-5), 4.22–4.15 (m, 2H, H-6’a, H-6’b), 4.19 (d, 1H, J 17.75
Hz, H-5a), 4.01 (d, 1H, J 17.75 Hz, H-5b), 2.08–1.95 (4×CH3CO); 13C NMR (DMSO-d6): δ
171.7 (C=O lactam), 169.9–169.4 (4×COCH3), 165.7 (C-6”), 164.4 (C-1”), 163.2 (C-2”),
163.1 (C-2, C=N), 136.0 (C-1””), 135.4 (C-1”’), 131.9 (C-3”’, C-5”’), 131.4 (C-4””), 129.5
(C-2”’, C-6”’), 128.9 (C-3””, C-5””), 127.6 (C-2””, C-6””), 125.1 (C-4”’), 108.4 (C-5”),
80.3 (C-1’), 72.9 (C-5’), 72.2 (C-3’), 67.6 (C-2’), 67.5 (C-4’), 61.6 (C-6’), 32.7 (C-5), 20.5–
1
20.1 (4×COCH3). (2’b): H NMR (DMSO-d6): δ 8.44 (s, 1H, H-5”), 8.40 (d, 2H, J 8.5 Hz,
H-2”’, H-6”’), 8.44–8.39 (m, 2H, H-2””, H-6””), 7.84 (d, 2H, J 8.5 Hz, H-3”’, H-5”’), 7.65-
7.64 (m, 3H, H-3””, H-4””, H-5””), 6.51 (d, 1H, J 9.25 Hz, H-2’), 5.97 (t, 1H, J 9.25 Hz, H-
1’), 5.59 (t, 1H, 9.5 Hz, H-3’), 5.25 (t, 1H, J 9.75 Hz, H-4’), 4.37-4.36 (m, 1H, H-5’), 4.22–
4.15 (m, 2H, H-6’a, H-6’b), 4.19 (d, 1H, J 17.75 Hz, H-5a), 4.01 (d, 1H, J 17.75 Hz, H-5b),
2.01–1.97 (4×CH3CO); 13C NMR (DMSO-d6): δ 171.7 (C=O lactam), 169.9–169.4
(4×COCH3), 165.7 (C-6”), 164.4 (C-1”), 163.2 (C-2”), 163.1 (C-2, C=N), 136.0 (C-1””),
135.4 (C-1”’), 131.9 (C-3”’, C-5”’), 131.4 (C-4””), 129.5 (C-2”’, C-6”’), 128.9 (C-3””,
C-5””), 127.6 (C-2””, C-6””), 125.1 (C-4”’), 108.4 (C-5”), 79.5 (C-1’), 73.0 (C-5’), 72.5
(C-3’), 67.3 (C-2’), 67.0 (C-4’), 61.6 (C-6’), 32.7 (C-5), 20.5–20.1 (4×COCH3).
Compounds 2c/2’c: Yield 66%; mp. 175–180 ºC, ratio of 2c/2’c isomers 7.5/2.5; IR
(KBr, cm–1): ν 1751, 1610, 1574, 1508, 1227, 1035; (2c): 1H NMR (DMSO-d6): δ 8.40–8.33
(m, 2H, J 7.75 Hz, H-2””, H-6””), 8.35 (s, 1H, H-5”), 8.34 (d, 2H, J 7.75 Hz, H-2”’, H-6”’),
7.62-7.60 (m, 3H, H-3””, H-4”” & H-5””), 7.47 (d, 2H, J 7.75 Hz, H-3”’, H-5”’), 6.38
(d, 1H, J 9.0 Hz, H-1’), 5.94 (t, 1H, J 9.25 Hz, H-2’), 5.65 (t, 1H, 9.5 Hz, H-3’), 5.02 (t, 1H,
J 9.75 Hz, H-4’), 4.39-4.38 (m, 1H, H-5’), 4.18–4.11 (m, 2H, H-6’a, H-6’b), 4.15 (d, 1H, J
18.0 Hz, H-5a), 3.96 (d, 1H, J 18.0 Hz, H-5b), 3.01 [septet, 1H, J 7.0 Hz, 4”’-CH(CH3)2],
2.05-1.92 (4×CH3CO), 1.28 [d, 6H, J 7.0 Hz, 4”’-CH(CH3)2]; 13C NMR (DMSO-d6): δ
171.7 (C=O lactam), 170.0–169.4 (4×COCH3), 165.7 (C-2”), 165.3 (C-6”), 163.3 (C-1”),
162.8 (C-2, C=N), 152.1 (C-4”’), 136.2 (C-1””), 133.8 (C-1”’), 131.2 (C-4””), 128.9 (C-3””,
C-5””), 127.7 (C-3”’, C-5”’), 127.5 (C-2””, C-6””), 126.9 (C-2””, C-6””), 108.2 (C-5”), 80.3
(C-1’), 72.9 (C-5’), 72.2 (C-3’), 67.6 (C-2’), 67.5 (C-4’), 61.6 (C-6’), 33.4 [4”-CH(CH3)2],
32.7 (C-5), 23.6 [4”-CH(CH3)2], 20.5-20.1 (4×COCH3). (2’c): 1H NMR (DMSO-d6): δ 8.40–
8.33 (m, 2H, J 7.75 Hz, H-2””, H-6””), 8.35 (s, 1H, H-5”), 8.34 (d, 2H, J 7.75 Hz, H-2”’,

Reaction of Substituted Thioureas with Ethyl Bromoacetate
1358
H-6”’), 7.62–7.60 (m, 3H, H-3””, H-4”” & H-5””), 7.47 (d, 2H, J 7.75 Hz, H-3”’, H-5”’),
6.50 (t, 1H, J 9.25 Hz, H-2’), 5.94 (t, 1H, J 9.25 Hz, H-1’), 5.55 (t, 1H, 9.5 Hz, H-3’), 5.21
(t, 1H, J 9.75 Hz, H-4’), 4.33-4.32 (m, 1H, H-5’), 4.18–4.11 (m, 2H, H-6’a, H-6’b), 4.15 (d,
1H, J 18.0 Hz, H-5a), 3.96 (d, 1H, J 18.0 Hz, H-5b), 3.01 [septet, 1H, J 7.0 Hz, 4”-
CH(CH3)2], 2.00–1.96 (4×CH3CO), 1.28 [d, 6H, J 7.0 Hz, 4”-CH(CH3)2]; 13C NMR
(DMSO-d6): δ 171.7 (C=O lactam), 170.0–169.4 (4×COCH3), 165.7 (C-2”), 165.3 (C-6”),
163.3 (C-1”), 162.8 (C-2, C=N), 152.1 (C-4”’), 136.2 (C-1””), 133.8 (C-1”’), 131.2 (C-4””),
128.9 (C-3””, C-5””), 127.7 (C-3”’, C-5”’), 127.5 (C-2””, C-6””), 126.9 (C-2””, C-6””),
108.2 (C-5”), 79.8 (C-1’), 73.0 (C-5’), 72.2 (C-3’), 67.6 (C-2’), 67.5 (C-4’), 61.6 (C-6’),
33.4 [4”-CH(CH3)2], 32.7 (C-5), 23.6 [4”-CH(CH3)2], 20.5–20.1 (4×COCH3).
Compounds 2d/2’d: Yield 59%; mp. 226-230 ºC, ratio of 2d/2’d isomers 7.5/2.5; IR
(KBr, cm–1): ν 1751, 1736, 1610, 1579, 1519, 1497, 1226, 1037; (2d): 1H NMR (DMSO-d6):
δ 8.52 (s, 1H, H-5”), 7.61 (s, 2”’-OH), 7.46–7.41 (m, 2H, H-2””, H-6””), 7.04–6.96 (m, 3H,
H-3”’, H-4”’ & H-5”’), 8.36-8.26 (d, 4H, H-4”’, H-6”’, H-2””, H-6””), 6.35 (d, 1H, J 9.0
Hz, H-1’), 5.93 (t, 1H, J 9.25 Hz, H-2’), 5.63 (t, 1H, 9.5 Hz, H-3’), 5.02 (t, 1H, J 10.0 Hz,
H-4’), 4.40–4.38 (m, 1H, H-5’), 4.23–4.11 (m, 2H, H-6’a, H-6’b), 4.16 (d, 1H, J 18.0 Hz,
H-5a), 4.00 (d, 1H, J 18.0 Hz, H-5b), 2.05–1.92 (4×CH3CO); 13C NMR (DMSO-d6): δ 171.6
(C=O lactam), 170.0–169.4 (4×COCH3), 164.7 (C-2”), 164.6 (C-6”), 164.0 (C-1”), 159.8
(C-2, C=N), 156.1 (C-2”’), 135.9 (C-1””), 131.5 (C-6”’), 129.0 (C-4”’, C-3””, C-5””), 128.7
(C-4””), 127.7 (C-2””, C-6””), 119.2 (C-5”’), 118.4 (C-1”’), 117.6 (C-3”’), 108.2 (C-5”),
80.3 (C-1’), 72.9 (C-5’), 72.2 (C-3’), 67.6 (C-2’), 67.5 (C-4’), 61.6 (C-6’), 32.7 (C-5), 20.
1
5–20.1 (4×COCH3). (2’d): H NMR (DMSO-d6): δ 8.52 (s, 1H, H-5”), 7.61 (s, 2”’-OH),
7.46-7.41 (m, 2H, H-2””, H-6””), 7.04-6.96 (m, 3H, H-3”’, H-4”’, H-5”’), 8.36-8.26 (d, 4H,
H-4”’, H-6”’, H-2””, H-6””), 6.44 (d, 1H, J 9.5 Hz, H-2’), 5.92 (t, 1H, J 9.0 Hz, H-1’), 5.56
(t, 1H, 9.25 Hz, H-3’), 5.10 (t, 1H, J 9.75 Hz, H-4’), 4.34-4.32 (m, 1H, H-5’), 4.23–4.11 (m,
2H, H-6’a, H-6’b), 4.16 (d, 1H, J 18.0 Hz, H-5a), 4.00 (d, 1H, J 18.0 Hz, H-5b), 2.05–1.92
(4×CH3CO); 13C NMR (DMSO-d6): δ 172.0 (C=O lactam), 170.0–169.4 (4×COCH3), 164.7
(C-2”), 164.6 (C-6”), 164.0 (C-1”), 159.8 (C-2, C=N), 156.1 (C-2”’), 135.9 (C-1””), 131.5
(C-6”’), 129.0 (C-4”’, C-3””, C-5””), 128.7 (C-4””), 127.7 (C-2””, C-6””), 119.2 (C-5”’),
118.4 (C-1”’), 117.6 (C-3”’), 108.2 (C-5”), 80.3 (C-1’), 72.9 (C-5’), 72.2 (C-3’), 67.6
(C-2’), 67.5 (C-4’), 61.6 (C-6’), 32.7 (C-5), 20.5–20.1 (4×COCH3).
Compounds 2e/2’e: Yield 54%; mp. 183–183 ºC, ratio of 2e/2’e isomers 7.5/2.5; IR
(KBr, cm–1): ν 1749, 1742, 1694, 1607, 1580, 1568, 1518, 1508, 1237, 1033; (2e): 1H NMR
(DMSO-d6): 8.46-8.37 (m, 2H, H-2”’, H-6”’), 8.42 (d, 2H, J 8.25 Hz, H-2””, H-6””), 8.37
(s, 1H, H-5”), 8.44-8.39 (m, 2H, H-2”’, H-6”’), 7.66–7.61 (m, 2H, H-4”’, H-5”’), 7.15
(d, 2H, J 8.25 Hz, H-3””, H-5””), 6.42 (d, 1H, J 9.0 Hz, H-1’), 5.97 (t, 1H, J 9.25 Hz, H-2’),
5.68 (t, 1H, 9.25 Hz, H-3’), 5.02 (t, 1H, J 9.75 Hz, H-4’), 4.40–4.38 (m, 1H, H-5’), 4.17–
4.11 (m, 2H, H-6’a, H-6’b), 4.19 (d, 1H, J 17.75 Hz, H-5a), 4.01 (d, 1H, J 17.75 Hz, H-5b),
3.88 (4””-OCH3), 2.05–1.92 (4×CH3CO); 13C NMR (DMSO-d6): δ 171.7 (C=O lactam),
169.9–169.4 (4×COCH3), 165.3 (C-2”), 163.7 (C-6”), 163.2 (C-1”), 162.8 (C-2, C=N),
162.0 (C-4””), 134.5 (C-1”’), 133.9 (C-3”’), 130.8 (C-2”’), 130.7 (C-5”’), 129.4 (C-2””,
C-6””), 128.3 (C-4”’), 127.9 (C-1””), 126.0 (C-6”’), 114.3 (C-3””, C-5””), 107.8 (C-5”),
80.3 (C-1’), 72.9 (C-5’), 72.3 (C-3’), 67.6 (C-2’), 67.5 (C-4’), 61.6 (C-6’), 55.4 (4””-OCH3),
1
32.7 (C-5), 20.5–20.1 (4×COCH3). (2’e): H NMR (DMSO-d6): 8.46-8.37 (m, 2H, H-2”’,
H-6”’), 8.42 (d, 2H, J 8.25 Hz, H-2””, H-6””), 8.37 (s, 1H, H-5”), 8.44–8.39 (m, 2H, H-2”’,
H-6”’), 7.66-7.61 (m, 2H, H-4”’, H-5”’), 7.15 (d, 2H, J 8.25 Hz, H-3””, H-5””), 6.49 (d, 1H, J 9.0

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NGUYEN DINH THANH
Hz, H-2’), 5.97 (t, 1H, J 9.25 Hz, H-1’), 5.56 (t, 1H, 9.25 Hz, H-3’), 5.22 (t, 1H, J 9.75 Hz,
H-4’), 4.34–4.32 (m, 1H, H-5’), 4.17–4.11 (m, 2H, H-6’a, H-6’b), 4.19 (d, 1H, J 17.75 Hz,
H-5a), 4.01 (d, 1H, J 17.75 Hz, H-5b), 3.88 (4””-OCH3), 1.98–1.95 (4×CH3CO); 13C NMR
(DMSO-d6): δ 171.7 (C=O lactam), 169.9–169.4 (4×COCH3), 165.3 (C-2”), 163.7 (C-6”),
163.2 (C-1”), 162.8 (C-2, C=N), 162.0 (C-4””), 134.5 (C-1”’), 133.9 (C-3”’), 130.8 (C-2”’),
130.7 (C-5”’), 129.4 (C-2””, C-6””), 128.3 (C-4”’), 127.9 (C-1””), 126.0 (C-6”’), 114.3 (C-
3””, C-5””), 107.8 (C-5”), 79.9 (C-1’), 73.0 (C-5’), 72.3 (C-3’), 67.6 (C-2’), 67.5 (C-4’),
61.2 (C-6’), 55.4 (4””-OCH3), 32.7 (C-5), 20.5–20.1 (4×COCH3).
Compounds 2f/2’f: Yield 66%; mp. 219–221 ºC, ratio of 2f/2’f isomers 7.6/2.4; IR
1
(KBr, cm–1): ν 1752, 1740, 1591, 1577, 1567, 1513, 1237, 1223, 1032; (2f): H NMR
(DMSO-d6): δ 8.41 (s, 1H, H-5”), 8.35 (d, 4H, J 8.25 Hz, H-2”’, H-6”’, H-2””, H-6””), 7.80
(d, 4H, J 8.25 Hz, H-3”’, H-5”’, H-3””, H-5””), 6.38 (d, 1H, J 9.0 Hz, H-1’), 5.93 (t, 1H, J
9.25 Hz, H-2’), 5.65 (t, 1H, 9.5 Hz, H-3’), 5.02 (t, 1H, J 9.75 Hz, H-4’), 4.39–4.37 (m, 1H,
H-5’), 4.18–4.11 (m, 2H, H-6’a, H-6’b), 4.16 (d, 1H, J 18.0 Hz, H-5a), 3.97(d, 1H, J 18.0
Hz, H-5b), 2.05–1.92 (4×CH3CO); 13C NMR (DMSO-d6): δ 171.7 (C=O lactam), 169.9–
169.4 (4×COCH3), 164.6 (C-4”, C-6”), 163.3 (C-2”), 163.1 (C-2, C=N), 135.3 (C-1”’,
C-1””), 131.9 (C-3”’, C-5”’, C-3””, C-5””), 129.6 (C-2”’, C-6”’, C-2””, C-6””), 125.2
(C-4”’, C-4””), 108.4 (C-5”), 80.3 (C-1’), 72.9 (C-5’), 72.2 (C-3’), 67.6 (C-2’), 67.5 (C-4’),
1
61.6 (C-6’), 32.7 (C-5), 20.5–20.1 (4×COCH3). (2’f): H NMR (DMSO-d6): δ 8.41 (s, 1H,
H-5”), 8.35 (d, 4H, J 8.25 Hz, H-2”’, H-6”’, H-2””, H-6””), 7.80 (d, 4H, J 8.25 Hz, H-3”’,
H-5”’, H-3””, H-5””), 6.47 (t, 1H, J 9.25 Hz, H-2’), 5.93 (t, 1H, J 9.25 Hz, H-1’), 5.55
(t, 1H, 9.25 Hz, H-3’), 5.21 (t, 1H, J 9.75 Hz, H-4’), 4.34-4.32 (m, 1H, H-5’), 4.18–4.11 (m,
2H, H-6’a, H-6’b), 4.16 (d, 1H, J 18.0 Hz, H-5a), 3.97(d, 1H, J 18.0 Hz, H-5b), 2.05–1.92
(4×CH3CO); 13C NMR (DMSO-d6): δ 171.7 (C=O lactam), 169.9–169.4 (4×COCH3), 164.6
(C-1”, C-6”), 163.3 (C-2”), 163.1 (C-2, C=N), 135.3 (C-1”’, C-1””), 131.9 (C-3”’, C-5”’,
C-3””, C-5””), 129.6 (C-2”’, C-6”’, C-2””, C-6””), 125.2 (C-4”’, C-4””), 108.4 (C-5”), 79.8
(C-1’), 72.9 (C-5’), 72.2 (C-3’), 67.6 (C-2’), 67.5 (C-4’), 61.6 (C-6’), 32.7 (C-5), 20.5–20.1
(4×COCH3).
Compounds 2g/2’g: Yield 68%; mp. 229–231 ºC, ratio of 2g/2’g isomers 7.5/2.5; IR
(KBr, cm–1): ν 1747, 1739, 1694, 1610, 1591, 1571, 1530, 1500, 1239, 1068; (2g): 1H NMR
(DMSO-d6): δ 8.32 (d, 2H, J 8.5 Hz, H-2”’, H-6”’), 8.28 (d, 2H, J 8.5 Hz, H-2””, H-6””),
8.12 (s, 1H, H-5”), 7.78 (d, 2H, J 8.5 Hz, H-3””, H-5””), 6.84 (d, 2H, J 8.5 Hz, H-3”’,
H-5”’), 6.36 (d, 1H, J 9.0 Hz, H-1’), 5.93 (t, 1H, J 9.5 Hz, H-2’), 5.64 (t, 1H, 9.75 Hz, H-3’),
5.00 (t, 1H, J 10.0 Hz, H-4’), 4.38-4.37 (m, 1H, H-5’), 4.17–4.10 (m, 2H, H-6’a, H-6’b),
4.13 (d, 1H, J 17.75 Hz, H-5a), 3.95 (d, 1H, J 17.75 Hz, H-5b), 3.04 (s, 6H, 4”’-NMe2),
2.06–1.92 (4×CH3CO); 13C NMR (DMSO-d6): δ 171.7 (C=O lactam), 169.9–169.4
(4×COCH3), 165.7 (C-6”), 163.4 (C-4”), 163.2 (C-2”), 162.3 (C-2, C=N), 152.4 (C-4”’),
135.8 (C-1””), 131.8 (C-3””, C-5””), 129.5 (C-2”’, C-6”’), 128.9 (C-2””, C-6””), 124.6
(C-1”’), 122.6 (C-4””), 108.4 (C-5”), 80.3 (C-1’), 72.9 (C-5’), 72.3 (C-3’), 67.6 (C-2’), 67.5
1
(C-4’), 61.7 (C-6’), 40.0 (4””-NMe2), 32.6 (C-5), 20.5–20.1 (4×COCH3). (2’g): H NMR
(DMSO-d6): δ 8.32 (d, 2H, J 8.5 Hz, H-2”’, H-6”’), 8.28 (d, 2H, J 8.5 Hz, H-2””, H-6””),
8.12 (s, 1H, H-5”), 7.78 (d, 2H, J 8.5 Hz, H-3””, H-5””), 6.84 (d, 2H, J 8.5 Hz, H-3”’,
H-5”’), 6.48 (d, 1H, J 9.25 Hz, H-2’), 5.93 (t, 1H, J 9.5 Hz, H-1’), 5.54 (t, 1H, 9.75 Hz,
H-3’), 5.20 (t, 1H, J 10.0 Hz, H-4’), 4.35–4.30 (m, 1H, H-5’), 4.17–4.10 (m, 2H, H-6’a,
H-6’b), 4.13 (d, 1H, J 17.75 Hz, H-5a), 3.95 (d, 1H, J 17.75 Hz, H-5b), 3.04 (s, 6H, 4”’-
NMe2), 1.98-1.93 (4×CH3CO); 13C NMR (DMSO-d6): δ 171.7 (C=O lactam), 169.9–169.4

Reaction of Substituted Thioureas with Ethyl Bromoacetate
1360
(4×COCH3), 165.7 (C-6”), 163.4 (C-1”), 163.2 (C-2”), 162.3 (C-2, C=N), 152.4 (C-4”’),
135.8 (C-1””), 131.8 (C-3””, C-5””), 129.5 (C-2”’, C-6”’), 128.9 (C-2””, C-6””), 124.6
(C-1”’), 122.6 (C-4””), 108.4 (C-5”), 80.3 (C-1’), 72.9 (C-5’), 72.3 (C-3’), 67.6 (C-2’), 67.5
(C-4’), 61.7 (C-6’), 40.0 (4””-NMe2), 32.6 (C-5), 20.5–20.1 (4×COCH3).
Results and Discussion
Required N-(per-O-acetyl-
(1a-g) were prepared as already described in 7 steps9 by the nucleophilic addition of
corresponding 2-amino-4’,6’-diarylpyrimidines on 2,3,4,6-tetra-O-acetyl- -D-glucopyranosyl
β-D-glucopyranosyl)-N’-(4’,6’-diarylpyrimidine-2’-yl)thioureas
β
isothiocyanate using microwave assisted method for several minutes in dried dioxane. The
reaction of ethyl bromoacetate with corresponding thioureas (1a-g) lead to new
3-(2’,3’,4’,6’-tetra-O-acetyl-β
thiazolidin-4-ones (2a-g) and 2-(2’,3’,4’,6’-tetra-O-acetyl-
-D-glucopyranosyl)-2-(4”,6”-diphenylpyrimidin-2”-ylimino)
-D-glucopyranosyl-1’-imino)-3-
β
(4”,6”-diphenylpyrimidin-2”-yl)thiazolidin-4-ones (2’a-g) (Scheme 1). We used chloroform
as the reaction medium and molar ratios of ethyl bromoacetate and thioureas 1a-g in 3:1
ratio in order to obtain the higher transformation yields. Reaction mixtures were stirred in
room temperature for one hour, after that, heated with reflux for 8-10 h. A reaction time of
over 10 h at reflux in chloroform was kept since a longer time did not improve the yield. The
appearance of white precipitate in the reaction beginning was the evidence indicating the
reaction was taken place. The isomeric products 2a-g and 2’a-g were insoluble in ethanol,
methanol, it facilitated for purification. Reaction yields are 50-68%. These isomers have
some similar features in structure which made the separation of these isomers to become
difficult. When solvent systems were changed from n-hexane-acetone to toluene-ethyl
acetate-formic acid, these isomers were always appeared in unique spot on TLC plate.
R1
OAc
N
O
AcO
N
AcO
AcO
OAc
N
R1
N
R2
A
O
S
O
N
N
AcO
AcO
BrCH2COOEt
CHCl3,
NH
NH
2a−g
OAc
B
∆
R2
S
OAc
R1
1a−g
O
AcO
AcO
N
N
S
AcO
N
N
O
1, 2 and 2': R1, R2=4"-F, H (
4"-OMe, 3""-Cl (
a
); 4"-Br, H (
b
); 4"-iPr, H (
c
); 2"-OH, H (
d
);
R2
e
); 4"-Br, 4""-Br (
f
); 4"-NMe2, 4""-Br ( )
g
2'a−g
Scheme 1
IR spectra show the characteristic absorption bands at ν=1752-1739 cm–1 (νC=O ester),
1694-1690 cm–1 (νC=O lactam), 1610-1607 cm–1 (νC=N), 1575-1508 cm–1 (νC=C), 1239-1227
and 1033-1035 cm–1 (νCOC ester). The evidences that confirm the success of reactions are the
absence of NH bands in IR spectra at ν=3340-3320 cm–1 and chemical shifts of NH
(thiourea) at δ=9-10 ppm (in 1H NMR spectra). Other evidence is the disappearance of C=S
signals at δ=206-208 ppm and the appearance of C=N signals at δ=163.9-160.0 ppm (in 13
C
1
NMR spectra). The H and 13C NMR spectral elucidations of these products indicated the
presence of two isomers in each obtained product. The isomers 2a-g and 2’a-g were distinguished

1361
NGUYEN DINH THANH
one isomer from another by chemical shits of protons H-1’ and H-2’ on pyranose ring. In
isomer 2a-g resonance signals of proton H-1’ show at δ=6.42–6.35 ppm and the one of
proton H-2’ show at δ=5.97-5.92 ppm, while protons H-1’ and H-2’ in isomer 2’a-g had
chemical shifts at δ=5.97-5.92 ppm and 6.51-6.44 ppm, respectively. Proton H-1’ in isomers
2’a-g were shielded more strongly by diamagnetic anisotropy of imino group and its
resonance signal was upfield, while this effect was absent in isomer 2a-g, so the resonance
signals of proton H-1’ was downfield.
Conclusion
We have performed a efficient method for the reaction of (2,3,4,6-tetra-O-acetyl-β-D-
glucopyranosyl)thioureas containing pyrmidine ring with ethyl bromoacetate under
refluxing conditions. It’s shows that the obtained 2-minothiazolidin-4-ones were two
isomers and their ration could be found using 1H NMR spectra.
Acknowledgment
Financial support for this work (104.01-2010.50) was provided by Vietnam's National
Foundation for Science and Technology Development (NAFOSTED).
References
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