Synthesis of novel glycosyl imidazolidine-2,4,5-trione derivatives

Article abstract of DOI:10.14233/ajchem.2015.16824

A series of glycosyl imidazolidine-2,4,5-trione derivatives were achieved by condensing per-O-acetylated glucosamine, triphosgene, amines and oxalyl chloride. The convenient and efficient method afforded the desired products with good to excellent yields

Full text of DOI:10.14233/ajchem.2015.16824

Asian Journal of Chemistry; Vol. 27, No. 1 (2015), 161-165
ASIAN JOURNAL OF CHEMISTRY
http://dx.doi.org/10.14233/ajchem.2015.16824
Synthesis of Novel Glycosyl Imidazolidine-2,4,5-Trione Derivatives
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WEI WEI LIU1,2,*, QIANG ZHANG , FENG GONG , YUN FENG HUO , CHUAN ZHOU TAO , ZHI LING CAO and DA HUA SHI
1School of Chemical Engineering, Huaihai Institute of Technology, Lianyungang 222005, P.R. China
2Department of Chemical Engineering, China University of Mining and Technology, Xuzhou 221116, P.R. China
*Corresponding author: E-mail: liuww2007ly@aliyun.com
Received: 5 December 2013;
Accepted: 21 April 2014;
Published online: 26 December 2014;
AJC-16528
A series of glycosyl imidazolidine-2,4,5-trione derivatives were achieved by condensing per-O-acetylated glucosamine, triphosgene,
amines and oxalyl chloride. The convenient and efficient method afforded the desired products with good to excellent yields and the
described compounds were prepared for the first time in this work. Satisfactory IR, 1H NMR, 13C NMR, ESI-MS spectra were obtained for
all compounds described.
Keywords: Per-O-acetylated glucosamine, Imidazolidine-2,4,5-trione, Glycosyl imidazolidine-2,4,5-trione derivatives.
These novel compounds contained with specific structural units
INTRODUCTION
were expected to exhibit biological activity in the future. The
Imidazolidine-2,4,5-trione and their derivatives are impor-
structures of products have also been fully characterized by
IR, 1H NMR 13C NMR and ESI-MS.
tant heterocylic compounds in organic and medicinal chemistry
due to their broad spectrum of biological activity including
antitumor1, inhibition of aldose reductase2, suppression of
EXPERIMENTAL
thymidine phosphorylase3. Even some special derivatives of
imidazolidine-2,4,5-trione showed an interesting property as
highly thermally stable polymers4 containing the unit of imida-
zolidine-2,4,5-trione with improved chemical resistance in
organic solvents. Simultaneously, D-glucosamine and its
N-substituted derivatives are found in numerous biologically
active molecules5 such as cell surface N-glycoproteins, proteo-
glycans, glycosylphosphatidylinositol (GPI) anchors,
glycosphingolipids, lipopolysaccharides and chitin/chitosan6.
Since derivatives of imidazolidine-2,4,5-trione and D-
glucosamine and its N-substituted derivatives showed diverse
ranges of biological properties, compounds containing both
imidazolidine-2,4,5-trione and glycosyl would provide novel
leading structures for medicinal research. A careful literature
survey revealed that imidazolidine-2,4,5-trione and its deriva-
tives have rarely been studied due to synthetic diffculty and
low yield in the past. To the best of our knowledge, the synthesis
of compounds containing both imidazolidine-2,4,5-trione and
glycosyl have not been investigated. As a part of our program
directed at the design and synthesis of carbonyl compounds7,
here we report a convenient and practical protocol for the
synthesis of glycosyl imidazolidine-2,4,5-trione derivatives via
the reactions of per-O-acetylated glucosamine, triphosgene,
amines and oxalyl chloride under basic condition (Scheme-I).
Commercial solvents and reagents were used as received.
Oxalyl chloride was purchased from Alpha Aesar Chemicals
Co. Ltd. (Tianjin, China) while triphosgene and amines were
purchased from AladdinTM Chemicals Co. Ltd. (Shanghai,
China). Melting points are uncorrected. IR spectra were taken
on a FTIR-Tensor 27 spectrometer in KBr pellets and reported
in cm-1. 1H NMR (13C NMR) spectra were measured on a Bruker
ACF 300 MHz spectrometer using TMS as an internal standard
and CDCl3-d6 as solvent. J values are in Hz. Chemical shifts
are expressed in ppm downfield from internal standard TMS.
HRMS (ESI) was determined by using Agilent 6540 Q-TOF
mass spectrometer.
Procedure for reaction of 1 with 2:To a vigorously stirred
solution of 1,3,4,6-tetra-O-acetyl-2-amino-2-deoxy-β-D-
glucopyranose hydrochloride 1 (1.8 mmol) in CH2Cl2 (18 mL)
and saturated aqueous solution of NaHCO3 (18 mL) was added
in triphosgene (0.66 mmol) in an ice bath to composite glycosyl
isocyanate. After this period, the TLC analysis of the mixture
showed the reaction to be completed. Then the organic layer
was separated, washed with water, dried over MgSO4 and
filtered.At last, amines 2 (2 mmol) in CH2Cl2 was slowly added
dropwise to the separated organic layer at room temperature.
Determining the reaction of raw materials completely, removing

162 Liu et al.
Asian J. Chem.
the solvent, crude products isolated by filtration was purified
to obtain glycosyl ureas by column chromatography (silica
gel 200-300 mesh, petroleum ether/EtOAc = 2:1).
151.39, 132.77 132.23, 130.96, 130.42, 128.49, 127.37, 89.48,
72.76, 70.45, 67.90, 61.48, 55.32, 21.16, 21.08, 20.93, 20.86;
ESI-MS (m/z): Calcd. for [M + Na]+ C23H24N2O12NaCl:
577.0832, found 577.0830.
General procedure for synthesis of glycosyl imidazo-
lidine-2,4,5-triones (3):A solution of glycosyl ureas obtained
from the reaction of compounds 1 with 2 was stirred in CH2Cl2
was slowly added dropwise to the mixture of oxalyl chloride
in CH2Cl2, then refluxing. When the TLC analysis of the
mixture showed the reaction to be completed, removing the
solvent, purifying crude products by column chromatography
(silica gel 200-300 mesh, petroleum ether/EtOAc = 3:1), giving
the desired products 3.
1-(4-Bromophenyl)-3-(1,3,4,6-tetra-O-acetyl-2-deoxy-
β-D-glucopyranos-2-yl)imidazolidine-2,4,5-trione (3e):
Yellow solid, m.p. 100-102 °C; IR (KBr, νmax, cm-1): 2967,
1
1746, 1606, 1513, 1409, 1224, 1037; H NMR (DMSO-d6,
300 MHz) δ: 7.78 (d, J = 8.6 Hz, 2H, ArH), 7.34 (d, J = 8.6
Hz, 2H, ArH), 6.12 (d, J = 8.9 Hz, 1H, H1), 5.91-5.51 (m, 1H,
H3), 5.01 (m, 1H, H4), 4.42-4.11 (m, 3H, H5, H6, H6'), 4.03
(d, J = 11.4 Hz, 1H, H2), 1.99 (4s, 12H, Ac); 13C NMR
(CDCl3-d6, 75 MHz,) δ: 171.42, 170.99, 169.64, 169.24,
156.01, 154.39, 133.01, 128.83, 127.68, 123.64, 89.81, 72.80,
71.17, 67.63, 61.47, 55.52, 21.28, 21.09, 20.95, 20.89; ESI-
MS (m/z): Calcd. for [M + Na]+ C23H24N2O12NaBr: 621.0327,
found 621.0330.
1-(4-Fluorophenyl)-3-(1,3,4,6-tetra-O-acetyl-2-deoxy-
β-D-glucopyranos-2-yl)imidazolidine-2,4,5-trione (3f):
White solid, m.p. 98-100 °C; IR (KBr, νmax, cm-1): 2960, 1748,
1596, 1503, 1404, 1218, 1038; 1H NMR (DMSO-d6, 300 MHz)
δ: 7.41 (d, J = 6.8 Hz, 4H, ArH), 6.13 (d, J = 8.9 Hz, 1H, H1),
5.75 (m, 1H, H3), 5.01 (m, 1H, H4), 4.40-4.11 (m, 3H, H5,
H6, H6'), 4.10-3.91 (m, 1H, H2), 1.99 (4s, 12H,Ac); 13C NMR
(CDCl3-d6, 75 MHz) δ: 171.37, 170.98, 169.65, 169.26, 164.54,
161.22, 156.15, 154.69, 152.23, 128.32, 125.67, 117.06,
116.76, 89.79, 72.74, 71.12, 67.66, 61.46, 55.46, 21.24, 21.04,
20.91, 20.85; ESI-MS (m/z): Calcd. for [M + Na]+
C23H24N2O12NaF: 561.1127, found 561.1131.
1-Phenyl-3-(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-
glucopyranos-2-yl)imidazolidine-2,4,5-trione (3a): White
solid, m.p. 98-100 °C; IR (KBr, νmax, cm-1): 2964, 1732, 1597,
1
1502, 1403, 1216, 1038; H NMR (DMSO-d6, 300 MHz) δ:
7.62-7.43 (m, 2H, ArH), 7.37 (d, J = 7.9 Hz, 2H, ArH), 6.15
(d, J = 8.8 Hz, 1H, H1), 5.84-5.61 (m, 1H, H3), 5.01 (t, J = 9.4
Hz, 1H, H4), 4.26 (ddd, J = 19.6, 17.9, 10.4 Hz, 3H, H5, H6,
H6'), 4.02 (dd, J = 12.3, 4.5 Hz, 1H, H2), 2 (4s, 12H, Ac); 13C
NMR (CDCl3-d6, 75 MHz) δ: 171.24, 170.95, 169.66, 169.21,
156.28, 154.76, 152.33, 129.75, 126.26, 89.78, 72.70, 71.02,
67.75, 61.48, 55.38, 21.23, 21.04, 20.90, 20.84, 14.51; ESI-
MS (m/z): Calcd. for [M + Na]+ C23H24N2O12Na: 543.1221,
found 543.1226.
1-(4-Chlorophenyl)-3-(1,3,4,6-tetra-O-acetyl-2-deoxy-
β-D-glucopyranos-2-yl)imidazolidine-2,4,5-trione (3b):
Yellow solid, m.p. 95-96 °C; IR (KBr, νmax, cm-1): 2958, 1746,
1
1597, 1535, 1496, 1405, 1221, 1077; H NMR (DMSO-d6,
300 MHz) δ: 7.63 (d, J = 8.7 Hz, 2H, ArH), 7.39 (d, J = 8.7
Hz, 2H, ArH), 6.11 (d, J = 8.9 Hz, 1H, H1), 5.73 (m, 1H, H3),
4.99 (m, 1H, H4), 4.36-4.08 (m, 3H, H5, H6, H6'), 4.01 (d,
J = 11.1 Hz, 1H, H2), 1.97 (4s, 12H, Ac); 13C NMR (DMSO-
d6, 75 MHz) δ: 170.82, 170.53, 170.11, 169.59, 156.95, 152.97,
134.20, 130.08, 129.09, 89.20, 72.21, 69.21, 62.02, 53.99,
21.81, 21.60, 21.28, 21.20; ESI-MS (m/z): Calcd. for [M +
Na]+ C23H24N2O12NaCl: 577.0832, found 577.0833.
1-(3-Chlorophenyl)-3-(1,3,4,6-tetra-O-acetyl-2-deoxy-
β-D-glucopyranos-2-yl)imidazolidine-2,4,5-trione (3c):
Yellow solid, m.p. 92-94 °C; IR (KBr, νmax, cm-1): 2960, 1748,
1594, 1484, 1402, 1219, 1078; 1H NMR (DMSO-d6, 300 MHz)
δ: 7.67-7.54 (m, 2H, ArH), 7.45 (s, 1H, ArH), 7.41-7.29 (m,
1H, ArH), 6.12 (d, J = 8.9 Hz, 1H, H1), 5.76 (m, 1H, H3),
5.01 (m, 1H, H4), 4.39-4.12 (m, 3H, H5, H6, H6'), 4.03 (d, J
= 11 Hz, 1H, H2), 1.99 (4s, 12H,Ac); 13C NMR (CDCl3-d6, 75
MHz) δ: 171.44, 171.01, 169.65, 169.25, 155.95, 154.33,
135.36, 130.79, 129.97, 126.40, 124.35, 89.81, 72.80, 71.19,
67.61, 61.47, 55.56, 21.30, 21.11, 20.96, 20.90; ESI-MS (m/z):
Calcd. for [M + Na]+ C23H24N2O12NaCl: 577.0832, found
577.0834.
1-(2-Chlorophenyl)-3-(1,3,4,6-tetra-O-acetyl-2-deoxy-
β-D-glucopyranos-2-yl)imidazolidine-2,4,5-trione (3d):
Yellow solid, m.p. 93-95 °C; IR (KBr, νmax, cm-1): 2960, 1746,
1593, 1493, 1404, 1217, 1037; 1H NMR (DMSO-d6, 300 MHz)
δ: 7.80-7.66 (m, 1H, ArH), 7.66-7.45 (m, 3H, ArH), 6.26-6.15
(d, J = 8.9 Hz, 1H, H1), 5.78-5.63 (m, 1H, H3), 5.14-4.95 (m,
1H, H4), 4.41-4.29 (m, 1H, H6), 4.29-4.15 (m, 2H, H5, H6'),
4.10-3.96 (m, 1H, H2), 2.10-1.87 (m, 12H, Ac); 13C NMR
(CDCl3-d6, 75 MHz) δ: 170.99, 169.82, 169.69, 156.04, 154.33,
1-(2,4-Dichlorophenyl)-3-(1,3,4,6-tetra-O-acetyl-2-
deoxy-β-D-glucopyranos-2-yl)imidazolidine-2,4,5-trione
(3g): Pale yellow solid, m.p. 93-95 °C; IR (KBr, νmax, cm-1):
2961, 1743, 1610, 1516, 1407, 1218, 1035; 1H NMR (DMSO-
d6, 300 MHz) δ: 7.95 (m, 1H, ArH), 7.75-7.62 (m, 1H, ArH),
7.60-7.45 (m, 1H,ArH), 6.25 (d, J = 8.9 Hz, 0.56 H, H1), 6.12
(d, J = 8.5 Hz, 0.44 H, H1), 5.73 (m, 1H, H3), 5.16-4.90 (m,
1H, H4), 4.41-4.30 (m, 1H, H6), 4.23 (m, 2H, H5, H6'), 4.03
(d, J = 11.7 Hz, 1H, H2), 2.16-1.75 (m, 12 H, Ac); 13C NMR
(CDCl3-d6, 75 MHz) δ: 170.97, 169.68, 155.77, 153.98, 151.15,
137.80, 133.74, 131.28, 131.10, 131, 130.92, 128.88, 125.97,
89.52, 72.89, 70.60, 68, 67.66, 61.49, 55.55, 21.16, 21.08,
20.93, 20.87; ESI-MS (m/z): Calcd. for [M + Na]+
C23H22N2O12NaCl2: 611.0442, found 611.0446.
1-(3-Chloro-4-fluorophenyl)-3-(1,3,4,6-tetra-O-acetyl-
2-deoxy-β-D-glucopyranos-2-yl)imidazolidine-2,4,5-trione
(3h): Pale white solid, m.p. 92-94 °C; IR (KBr, νmax, cm-1):
2960, 1750, 1587, 1498, 1406, 1216, 1050; 1H NMR (DMSO-
d6, 300 MHz) δ: 7.75-7.51 (m, 2H, ArH), 7.40 (m, 1H, ArH),
6.10 (d, J = 8.9 Hz, 1H, H1), 5.74 (m, 1H, H3), 4.99 (m, 1H,
H4), 4.40-4.10 (m, 3H, H5, H6, H6'), 4.01 (d, J = 10.8 Hz,
13
1H, H2), 2.09-1.82 (4s, 12 H, Ac); C NMR (CDCl3-d6, 75
MHz) δ: 171.56, 171.03, 169.64, 169.28, 160.20, 156.85,
155.86, 154.32, 151.89, 128.74, 126.28, 122.61, 122.36,
117.87, 117.57, 89.82, 72.83, 71.22, 67.61, 61.50, 55.63,
21.27, 21.07, 20.93, 20.88; ESI-MS (m/z): Calcd. for [M +
Na]+ C23H22N2O12NaClF: 595.0738, found 595.0742.
1-(p-Tolyl)-3-(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-
glucopyranos-2-yl)imidazolidine-2,4,5-trione (3i): White
solid, m.p. 89-91 °C; IR (KBr, νmax, cm-1): 2960, 1738, 1517,

Vol. 27, No. 1 (2015)
Synthesis of Novel Glycosyl Imidazolidine-2,4,5-Trione Derivatives 163
1406, 1217, 1038; 1H NMR (DMSO-d6, 300 MHz) δ: 7.35 (d,
J = 8.3 Hz, 2H, ArH), 7.24 (d, J = 8.3 Hz, 2H, ArH), 6.14 d, J
= 8.9 Hz, 1H, H1), 5.89-5.50 (m, 1H, H3), 5.01 (m, 1H, H4),
4.25 (m, 3H, H5, H6, H6'), 4.11-3.94 (m, 1H, H2), 2.36 (s,
3H, CH3), 1.99 (4s, 12H, Ac); 13C NMR (CDCl3-d6, 75 MHz)
δ: 171.19, 170.93, 169.67, 169.22, 156.39, 154.92, 152.47,
139.95, 130.36, 127.20, 126.13, 89.78, 72.63, 70.98, 67.75,
61.43, 55.31, 21.53, 21.21, 21.02, 20.88, 20.82; ESI-MS (m/z):
calcd for [M + Na]+ C24H26N2O12Na: 557.1378, found
557.1382.
130.63, 118.38, 115.30, 112.25, 89.77, 72.68, 71.03, 67.74,
61.47, 55.83, 55.37, 21.23, 21.04, 20.90, 20.84; ESI-MS (m/z):
Calcd. for [M + Na]+ C24H26N2O13Na: 573.1327, found
573.1332.
1-(2-Methoxyphenyl)-3-(1,3,4,6-tetra-O-acetyl-2-deoxy-
β-D-glucopyranos-2-yl)imidazolidine-2,4,5-trione (3n).
White solid, m.p. 90-93 °C; IR (KBr, νmax, cm-1): 2946, 1745,
1
1600, 1508, 1465, 1404, 1221, 1039; H NMR (DMSO-d6,
300 MHz) δ: 7.52 (dd, J = 10.9, 4.9 Hz, 1H, ArH), 7.27 (m,
2H, ArH), 7.14-7.02 (m, 1H, ArH), 6.27 (d, J = 8.9 Hz, 0.58H,
H1), 6.20 (d, J = 8.9 Hz, 0.40 H, H1), 5.80-5.62 (m, 1H, H3),
5.13-4.97 (m, 1H, H4), 4.38-4.12 (m, 3H, H5, H6, H6'), 4.04
(m, 1H, H2), 3.77 (s, 3H, CH3O), 2.13-1.90 (m, 12H, Ac); 13C
NMR (CDCl3-d6, 75 MHz) δ: 170.98, 169.72, 168.81, 156.39,
155.06, 151.96, 132.19, 129.69, 129.53, 121.39, 118.01,
112.65, 89.62, 72.97, 70.53, 68.24, 67.88, 61.58, 56.31, 55.15,
21.15, 21.08, 20.94, 20.85, 20.79; ESI-MS (m/z): Calcd. for
[M + Na]+ C24H26N2O13Na: 573.1327, found 573.1331.
1-(3,4,5-Trimethoxyphenyl)-3-(1,3,4,6-tetra-O-acetyl-
2-deoxy-β-D-glucopyranos-2-yl)imidazolidine-2,4,5-trione
(3o): White solid, m.p. 99-101 °C; IR (KBr, νmax, cm-1): 2946,
1-(m-Tolyl)-3-(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-
glucopyranos-2-yl)imidazolidine-2,4,5-trione (3j): White
solid, m.p. 90-91 °C; IR (KBr, νmax, cm-1): 2960, 1738, 1610,
1
1494, 1403, 1218, 1038; H NMR (DMSO-d6, 300 MHz) δ:
7.43 (m, 1H, ArH), 7.30 (d, J = 7.4 Hz, 1H, ArH), 7.16 (d, J =
8 Hz, 2H, ArH), 6.14 (d, J = 8.8 Hz, 1H, H1), 5.74 (mz, 1H,
H3), 5.01 (m, 1H, H4), 4.37-4.12 (m, 3H, H5, H6, H6'), 4.09-
3.92 (m, 1H, H2), 2.37 (s, 3H, CH3), 2 (4s, 12H, Ac). 13C
NMR (CDCl3-d6, 75 MHz) δ: 171.24, 170.94, 169.65, 169.17,
156.33, 154.83, 152.37, 139.98, 130.57, 129.58, 126.80,
123.37, 89.82, 72.71, 71.06, 67.75, 61.48, 55.38, 21.64, 21.22,
21.03, 20.89, 20.83; ESI-MS (m/z): Calcd. for [M + Na]+
C24H26N2O12Na: 557.1378, found 557.1381.
1
2837, 1742, 1600, 1508, 1465, 1406, 1232, 1038; H NMR
(CDCl3-d6, 300 MHz) δ: 6.63 (s, 2H, ArH), 6.44 (d, J = 8.7
Hz, 1H, H1), 5.70 (t, 1H, H3), 5.26 (dd, J = 16.3, 6.5 Hz, 1H,
H4), 4.48-4.27 (m, 2H, H5, H6), 4.13 (d, J = 12.6 Hz, 1H,
H6'), 4.02-3.76 (m, 10 H, H2, 3CH3O), 2.08 (4s, 12 H, Ac);
13C NMR (CDCl3-d6, 75 MHz) δ: 171.39, 170.95, 169.60,
169.11, 156.14, 154.81, 153.94, 152.31, 139.02, 125.12, 104),
89.85, 72.87, 71.26, 67.69, 61.53, 61.24, 56.63, 55.54, 21.24,
21.05, 20.91; ESI-MS (m/z): Calcd. for [M + Na]+
C26H30N2O15Na: 633.1538, found 633.1537.
1-(o-Tolyl)-3-(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-
glucopyranos-2-yl)imidazolidine-2,4,5-trione (3k): White
solid, m.p. 90-92 °C; IR (KBr, νmax, cm-1): 2961, 1744, 1498,
1
1403, 1218, 1038; H NMR (DMSO-d6, 300 MHz) δ: 7.34
(m, 4H, ArH), 6.23 (d, J = 9 Hz, 1H, H1), 6.06 (d, J = 8.1 Hz,
1H, H1), 5.88-5.73 (m, 1H, H3), 5.72-5.56 (m, 1H, H3), 5.02
(m, 1H, H4), 4.27 (m, 3H, H5, H6, H6'), 4.11-3.96 (m, 1H,
H2), 2.16 (d, J = 13.4 Hz, 3H, CH3), 2.09-1.87 (m, 12H, Ac);
13C NMR (CDCl3-d6, 75 MHz) δ: 170.99, 169.65, 169.22,
169.09, 156.48, 154.87, 152.23, 136.32, 131.81, 130.81,
128.38, 127.51, 89.79, 72.80, 70.99, 67.83, 67.65, 61.51,
55.55, 21.18, 21.06, 20.92, 20.85, 17.86; ESI-MS (m/z): Calcd.
for [M + Na]+ C24H26N2O12Na: 557.1378, found 557.1382.
1-(4-Methoxyphenyl)-3-(1,3,4,6-tetra-O-acetyl-2-
deoxy-β-D-glucopyranos-2-yl)imidazolidine-2,4,5-trione
(3l). White solid, m.p. 89-91 °C; IR (KBr, νmax, cm-1): 2961,
1-(2,5-Dimethoxyphenyl)-3-(1,3,4,6-tetra-O-acetyl-2-
deoxy-β-D-glucopyranos-2-yl)imidazolidine-2,4,5-trione
(3p): White solid, m.p. 97-99 °C; IR (KBr, νmax, cm-1): 2961,
1
2842, 1747, 1593, 1513, 1465, 1400, 1228, 1038; H NMR
(CDCl3-d6, 300 MHz) δ: 7.06-6.89 (m, 2H, ArH), 6.80 (m,
1H, ArH), 6.41 (d, J = 8.8 Hz, 1H, H1), 5.88-5.61 (m, 1H,
H3), 5.21 (m, 1H, H4), 4.51-4.25 (m, 2H, H5, H6), 4.11 (m,
1H, H6'), 4.03-3.88 (m, 1H, H2), 3.83-3.70 (m, 6H, 2CH3O),
1
13
1731, 1608, 1497, 1397, 1212, 1036; H NMR (DMSO-d6,
2.19-1.91 (m, 12 H, Ac); C NMR (CDCl3-d6, 75 MHz) δ:
300 MHz) δ: 7.27 (d, J = 8.8 Hz, 2H, ArH), 7.09 (d, J = 8.9
Hz, 2H, ArH), 6.14 (d, J = 8.8 Hz, 1H, H1), 5.84-5.52 (m, 1H,
H3), 5.01 (m, 1H, H4), 4.38-4.11 (m, 3H, H5, H6, H6'), 4.03
(d, J = 11.2 Hz, 1H, H2), 3.80 (s, 3H, CH3O), 2 (4s, 12H, Ac);
13C NMR (CDCl3-d6, 75 MHz) δ: 171.29, 170.98, 169.65,
169.15, 160.43, 156.38, 155.02, 127.73, 122.22, 115.03, 89.84,
72.79, 71.15, 67.72, 61.50, 55.91, 55.40, 21.26, 21.07, 20.93,
20.87; ESI-MS (m/z): Calcd. for [M + Na]+ C24H26N2O13Na:
573.1327, found 573.1332.
1-(3-Methoxyphenyl)-3-(1,3,4,6-tetra-O-acetyl-2-
deoxy-β-D-glucopyranos-2-yl)imidazolidine-2,4,5-trione
(3m). White solid, m.p. 91-93 °C; IR (KBr, νmax, cm-1): 2958,
1746, 1603, 1508, 1467, 1405, 1216, 1040; 1H NMR (CDCl3-
d6, 300 MHz) δ: 7.41 (t, 1H, ArH), 7.05-6.84 (m, 3H, ArH),
6.44 (d, J = 8.8 Hz, 1H, H1), 5.70 (t, 1H, H3), 5.25 (t, 1H,
H4), 4.50-4.26 (m, 2H, H6, 5), 4.13 (d, J = 12.2 Hz, 1H, H6'),
3.97 (d, J = 8.1 Hz, 1H, H2), 3.84 (s, 3H, CH3O), 2.21-1.89
(4s, 12 H, Ac); 13C NMR (CDCl3-d6, 75 MHz) δ: 171.24,
170.96, 169.67, 169.21, 160.48, 156.24, 154.71, 152.23,
170.94, 169.74, 168.86, 156.36, 154.98, 153.89, 151.86
(s, 1H), 149.19, 118.33, 117.19, 115.19, 113.60, 89.56, 72.85,
70.46, 68.26, 67.89, 61.54, 56.78, 56.20, 55.12 (s, 2H), 21.12,
21.04, 20.90, 20.82, 20.75; ESI-MS (m/z): Calcd. for [M +
Na]+ C25H28N2O14Na: 603.1433, found 603.1437.
1-(Naphthalen-1-yl)-3-(1,3,4,6-tetra-O-acetyl-2-deoxy-
β-D-glucopyranos-2-yl)imidazolidine-2,4,5-trione (3q):
Yellow solid, m.p. 114-116 °C; IR (KBr, νmax, cm-1): 2961,
1748, 1600, 1512, 1470, 1406, 1223, 1037; 1H NMR (DMSO-
d6, 300 MHz) δ: 8.23-7.89 (m, 3H, ArH), 7.72-7.49 (m, 4H,
ArH), 6.24 (d, J = 8.8 Hz, 1H, H1), 5.93-5.82 (m, 1H, H3), 5.72
(m, 1H, H3), 5.01 (m, 1H, H4), 4.43-4.11 (m, 3H, H5, H6, H6'),
4.03 (d, J = 11.8 Hz, 1H, H2), 2.12-1.91 (m, 12H,Ac); 13C NMR
(CDCl3-d6, 75 MHz) δ: 171.69, 171.36, 170.98, 169.65, 169.41),
169.19, 156.59, 156.53, 155.56, 155.38, 134.73, 131.42, 129.79,
129.07, 128.15, 127.33, 127.07, 126.93, 126.03, 125.66, 121.84,
90.08, 72.79, 71.41, 67.76, 67.59, 61.51, 55.78, 21.30, 21.08,
21.01, 20.94; ESI-MS (m/z): Calcd. for [M + Na]+
C27H26N2O12Na: 593.1378, found 593.1383.

164 Liu et al.
Asian J. Chem.
1-[4-(Ethoxyl)phenyl]-3-(1,3,4,6-tetra-O-acetyl-2-
-3-(1,3,4,6-tetra-O-acetyl-2-deoxy-β-D-glucopyranos-2-
yl)imidazolidine-2,4,5-triones were synthesized in good to
excellent yields. The results are given in Table-1.
deoxy-β-D-glucopyranos-2-yl)imidazolidine-2,4,5-trione
(3r): White solid, m.p. 95-97 °C; IR (KBr, νmax, cm-1): 2982,
1743, 1609, 1514, 1478, 1408, 1217, 1041; 1H NMR (CDCl3-
d6, 300 MHz) δ: 7.28 (d, J = 9.6 Hz, 2H, ArH), 6.98 (m, 2H,
ArH), 6.40 (d, J = 8.8 Hz, H1), 5.77-5.61 (m, H3), 5.24 (m,
H4), 4.38 (m, 2H, H5, H6), 4.14 -3.90 (m, 4H, H6', H2, CH2),
2.10 (d, J = 2.2 Hz, 6H,Ac), 2.05 (s, 3H, Ac), 1.99 (s, 3H,Ac),
1.42 (m, 3H, CH3); 13C NMR (CDCl3-d6, 75 MHz) δ: 171.29,
170.96, 169.60, 169.05, 159.85, 154.98, 127.66, 121.99,
115.51, 89.89, 72.92, 71.23, 67.75, 64.18, 61.57, 55.47, 21.25,
21.07, 20.93, 20.86, 15.03; ESI-MS (m/z): Calcd. for [M +
Na]+ C25H28N2O13Na: 587.1484, found 587.1488.
TABLE-1
CLOSED-LOOP REACTION WITH
OXALYL CHLORIDE TO SYNTHESIZE 3
Compound
R
Yield (%)
85
C6H5
3a
3b
3c
3d
3e
3f
4-Cl-C6H4
3-Cl-C6H4
2-Cl-C6H4
4-Br-C6H4
87
82
77
80
4-F-C6H4
65
1-(3-Chloro-4-methylphenyl)-3-(1,3,4,6-tetra-O-
acetyl-2-deoxy-β-D-glucopyranos-2-yl)imidazolidine-2,4,5-
trione (3s):Yellow solid, m.p. 106-108 °C; IR (KBr, νmax, cm-1):
2,4-di-Cl -C6H3
3-Cl-4-F-C6H3
4-Me-C6H4
3-Me-C6H4
2-Me-C6H4
4-CH3O-C6H4
3-CH3O-C6H4
2-CH3O-C6H4
3,4,5-tri-MeO-C6H2
3,5-di-MeO-C6H3
Naphthalen-1-yl
4-C2H5O-C6H4
3-Cl-4-Me-C6H3
75
59
86
85
81
86
88
73
80
76
80
86
3g
3h
3i
1
3j
2960, 1747, 1574, 1500, 1407, 1217, 1052; H NMR
3k
3l
(CDCl3-d6, 300 MHz) δ: 7.43 (s, 1H, ArH), 7.36 (d, J = 8.2
Hz, 1H, ArH), 7.31-7.15 (m, 1H, ArH), 6.40 (d, J = 8.8 Hz,
1H, H1), 5.78-5.54 (m, 1H, H3), 5.37-5.07 (m, 1H, H4), 4.38
(m, 2H, H5, H6), 4.16-4.04 (m, 1H, H6'), 3.97 (d, J = 8.2 Hz,
1H, H2), 2.42 (s, 3H, CH3), 2.11 (d, J = 2.4 Hz, 6H, Ac), 2.06
(s, 3H, Ac), 2 (s, 3H, Ac); 13C NMR (CDCl3-d6, 75 MHz) δ:
171.42, 170.96, 169.58, 169.08, 155.99, 154.43, 138.21,
135.34, 131.82, 126.72, 124.35, 89.84, 72.94, 71.27, 67.69,
61.55, 55.61, 21.26, 21.08, 20.93, 20.86, 20.30; ESI-MS (m/z):
Calcd. for [M + Na]+ C24H25N2O12NaCl: 591.0988, found
591.0993.
3m
3n
3o
3p
3q
3r
3s
83
As shown in Table-1, we premeditated amines with electron-
withdrawing groups or electron-donating groups. The reaction
was detected by means of the TLC analysis of the mixture and
determined by the reaction of raw materials completely. It is
found that all amines containing either electron-withdrawing
group, electron-donating group or can be smoothly converted
to the desired products with satisfactory yields under the
analogous conditions. It is noteworthy that the present reaction
was accomplished under mild conditions and the method is
operationally simple with satisfactory yields. For a more in-
depth study of the reaction, a plausible mechanistic pathway9
to products 3 is illustrated in Scheme-II.
RESULTS AND DISCUSSION
On the basis of our previous experience, glycosyl imida-
zolidine-2,4,5-triones were synthesized by treatment of per-
O-acetylated glucosamine 1 and excess of triphosgene initially,
then processed with amines 2 to composite glycosyl isocya-
nate8 and the reaction was carried out in dichloromethane at
room temperature. After that, the glycosyl isocyanate purified
for closed-loop reaction with oxalyl chloride in dichloro-
methane at refluxing. Furthermore, the best reaction conditions
are summarized in Scheme-I.
Conclusion
To investigate the scope of this reaction, various glycosyl
imidazolidine-2,4,5-trione derivatives were employed under the
optimized reaction conditions and a series of new 1-substituted
In summary, we report a rapid and efficient protocol to
synthesize a series of novel glycosyl imidazolidine-2,4,5-
AcO
O
AcO
OAc
O
O
(1)BTC, R-NH2, DCM, RT,10-30min
OAc
NH2 HCl
AcO
AcO
N
AcO
AcO
(2) Oxalyl chloride, DCM, reflux,1-6h
O
N
R
O
1
2
3
Scheme-I: Synthesis of the compounds 3
O
O
RHN C N R'
O
RHN
N R'
O O
O
R
R
R'
N
N R'
(COCl)2
-HCl
N
N
H
N R'
H
Cl
O
O
-HCl
Cl
RHN
Cl
O O
O
O
O
Scheme-II: Proposed mechanism for products 3

Vol. 27, No. 1 (2015)
Synthesis of Novel Glycosyl Imidazolidine-2,4,5-Trione Derivatives 165
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Viruses, 2, 1011 (2010); (f) L. Liu, C.S. Bennett and C.H. Wong, Chem.
Commun., 21, (2006).
triones in good to excellent yields. Additionally the J values
of the pyranose ring are indicative of the preponderance of
the C1 conformations in solution. Also, the β configuration
of the products was verified by the J1,2 values around 8-9 Hz.
Given the fact that imidazolidine-2,4,5-triones have exhibited
biological activity, we anticipate that these new compounds
described in the present report would be valuable in further
pharmaceutical research.
4
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ACKNOWLEDGEMENTS
This work was supported by the Major Program of Natural
Science Foundation of Jiangsu Education Committee (No.
10KJA170003) Industrialization Projects of Scientific Research
in Colleges and universities of Jiangsu Province (No. JHB2012-
60), Scientific and Technological Research Project of Lianyun-
gang (No. CG1105) and the Project Funded by the Priority
Academic Program Development of Jiangsu Higher Education
Institutions.
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