Synthesis of New Gluco-, Galacto-, and mannopyranosylthiazoles, thiazolidinones, and pyranosylthiazlidin-4-ones from sugar thiosemicarbazone derivatives

Article abstract of DOI:10.1002/hc.21083

A new series of potentially biological active derivatives, namely alkyl-2-((4-oxo-2-(phenylimino)-3-(β-d-pyranosyl-2-ylamino) thiazolidine-5-ylidene)acetate (5a-f), 4-(4-bromophenyl)thiazol-2(3H)-ylidene) hydrazinyl)-β-d-pyranosyl (4a-c), and 5-(4-bromophenyl)-2-(phenylimino)-3- (β-d-pyranosyl-2-ylamino)thiazolidine-4-one (6) were synthesized via a reaction of the sugar thiosemicarbazone derivatives with 2,4′- dibromoacetophenone, dialkylacetylenedicarboxylate, and ethylbromoacetate, respectively. The structures of the synthesized compounds were established by spectroscopic methods (FT-IR, ¹H NMR, ¹³C NMR, and 2D NMR) and elemental analyses. Furthermore, the effect of various solvents at reflux and also ambient temperature on the reactions of the sugar thiosemicarbazone with 2,4′dibromoacetophenone, diethyl acetylenedicarboxylate, and dimethyl acetylenedicarboxylate was investigated.

Full text of DOI:10.1002/hc.21083

Heteroatom Chemistry
Volume 00, Number 0, 2013
Synthesis of New Gluco-, Galacto-, and
Mannopyranosylthiazoles, Thiazolidinones,
and Pyranosylthiazlidin-4-ones from Sugar
Thiosemicarbazone Derivatives
Ali Darehkordi, Mahin Ramezani, and Reza Ranjbar-Karimi
Department of Chemistry, Faculty of Science, Vali-e-Asr University, Rafsanjan 77176, Iran
Received 8 December 2012; revised 28 January 2013
INTRODUCTION
ABSTRACT: A new series of potentially biolog-
ical active derivatives, namely alkyl-2-((4-oxo-2-
(phenylimino)-3-(β-D-pyranosyl-2-ylamino)thiazo-
lidine-5-ylidene)acetate (5a–f), 4-(4-bromophenyl)
thiazol-2(3H)-ylidene)hydrazinyl)-β -D-pyranosyl
(4a–c), and 5-(4-bromophenyl)-2-(phenylimino)-3-
(β-D-pyranosyl-2-ylamino)thiazolidine-4-one (6) were
synthesized via a reaction of the sugar thiosemicar-
bazone derivatives with 2,4ꢀ-dibromoacetophenone,
dialkylacetylenedicarboxylate, and ethylbromoacetate,
respectively. The structures of the synthesized com-
pounds were established by spectroscopic methods
(FT-IR, 1H NMR, 13C NMR, and 2D NMR) and
elemental analyses. Furthermore, the effect of various
solvents at reflux and also ambient temperature on
the reactions of the sugar thiosemicarbazone with
2,4ꢀdibromoacetophenone, diethyl acetylenedicar-
boxylate, and dimethyl acetylenedicarboxylate was
Thiazoles are general heterocyclic compounds that
are found in various biologically active and natural
products like vitamin B1 (thiamine) [1]. The thia-
zole ring in the presence of its coenzyme also plays
an important role as an electron sink in the decar-
boxylation of α-keto acid [2]. Thiazole derivatives,
thiazolidine-4-one, and organic compounds contain-
ing the thiazole and thiazolidinone ring system are
used as antiviral agents, and some are used as pes-
ticides [3], antitumor, cytotoxic [4], antifungal [5],
antibacterial [6], antiparasitic [7], antitubercular [8],
analgesic, and anticancer [9] agents. Therefore, stud-
ies of the synthesis and pharmacology of thiazol-
2-imine derivatives and thiazolidine-4-one have at-
tracted increasing interest in recent years.
In the past few decades, the literature has been
enriched with increasing amounts of information
about the anticonvulsive activities of various sub-
stituted thiazole derivatives [10], the synthesis of
thiazole derivatives by various methods, and their
biological evaluation [11]. In 2003, a series of ary-
laminothiazoles were synthesized by Holla et al.
and found to be effective antibacterial and antiin-
flammatory agents [12]. Recently, the quantitative
structural–activity relationship analyses for fungici-
dal activities of 2-phenylimino-1 and 3-thiazolines
derivatives were carried out by Hahn and coworkers
[13]. The glycoconjugates also exerted important ef-
fects on many complex biological events [14] includ-
ing cellular recognition in the processes of immune
ꢁC
investigated.
2013 Wiley Periodicals, Inc. Het-
eroatom Chem. 00:1–8, 2013; View this article online
at wileyonlinelibrary.com. DOI 10.1002/hc.21083
Correspondence to: Ali Darehkordi; e-mail: adarehkordi@
yahoo.com, darehkordi@mail.vru.ac.ir.
Contract grant sponosr: Vali-e-Asr University of Rafsanjan Fac-
ulty Research Grant.
ꢁC
2013 Wiley Periodicals, Inc.
1

2
Darehkordi, Ramezani, and Ranjbar-Karimi
SCHEME 1 Synthesis of 4-bromothiazol-2-ylidene derivative.
response [15], inflammation, tumor metastasis, and
viral infections [16].
dichloromethane were used as the reaction medium.
In these reactions, cyclization products were not
obtained; however, the use of absolute ethanol as
a solvent gave the desired products. The structures
of compounds 4a–c were deduced from their
elemental analysis and their IR and 1H and 13C
NMR spectral data. In the 1H NMR spectra of
compounds 4a–c, the expected two doublets around
7 and 8 ppm corresponding to the NH groups and
one singlet at 7 ppm corresponding to the H C C
thiazole ring were observed whereas their 13C NMR
showed signals of thiazole ring imino groups around
170 ppm.
The formation of the 4-bromothiazol-2-ylidene
derivatives was verified by C H correlations experi-
ments. Figure 1 shows the C H correlations spectra
of 4a. Based on the C H correlations in Fig. 1, we
can unambiguously assign all chemical shift values
of carbon and proton atoms in the sugar ring.
To obtain thiazolidine derivatives, a series
of 4-oxothiazolidine-5-ylidene derivatives 5a–f
were synthesized (Scheme 2). Compounds 5a–f
were obtained by the reaction of dialkylacetylenedi-
In addition, glycosylation of proteins and lipids
is a key factor in modulating their structures and
functions [17]. However, there are a few reports on
the synthesis and pharmacology of the thiazol-2-
imines containing sugar moieties. Since thiazole and
thiazolidinone ring systems are known to be biologi-
cally active, we turned our attention to the synthesis
of such thiazol-2-imine derivatives for investigating
their biological activities and developing structure–
activity relationships. Our research group is hopeful
that this synthesis will provide new and fascinating
sulfur-containing drug candidates.
RESULTS AND DISCUSSION
β-D-Pyranosylhydrazinecarbothioamide 2a–2c and
N-phenyl-β-D-pyranosyl hydrazine carbothioamide
3a–3c were used as starting materials. These com-
pounds (2a–c and 3a–c) were obtained from the re-
action of D-glycopyranos derivatives and thiosemi-
carbazide or phenylthiosemicarbazide, respectively,
according to the known procedure in the literature
[18–20].
carboxylate with
pyranosidehydrazinecarbothioamides.
a
series of N-phenyl-β-D-
Several
The reaction of 2a–c with 2,4ꢀ-dibromo-
acetophenone was investigated (Scheme 1).
First, different solvents such as chloroform and
reports regarding the condensation of thiosemicar-
bazones with alkyl halides have pointed out that
the main products are of type 5a–f [21], resulting
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Synthesis of New Gluco-, Galacto-, and Mannopyranosylthiazoles, Thiazolidinones and Pyranosylthiazlidin-4-ones
3
FIGURE 1 (A) 1H-13C correlations spectra of 2-[N-(4-(4-bromo-phenyl)-3H-thiazol-2-ylidene]-D-glucopyranosyl, (B) sugar part
(expanded)
1
from cyclization at N-4. 2-(Dimethylhydrazono)-
3-phenylthiazol-4-one was obtained by refluxing
thiosemicarbazide with ethyl bromoacetate for 7
days in dichloromethane [22]. Saleh et al. reported
that substituted thioureas reacted with chloroacetic
acid in the presence of a weak base to produce
thiazolidine-4-one compounds with substitution at
N-4 [23].
Conversely, the cyclization at N-2 has been
scarcely reported. Moghaddam and Hojabri [24]
have reported cyclization at the N-2 position. A
detailed study of the condensation of thiosemicar-
bazides with ethyl bromoacetate to give N-2 iso-
mers as major products has been reported [25].
In conclusion, the reaction is mainly condensa-
tion followed by cyclization. Initially, the sulfur
atom from β-D-pyranosylhydrazinecarbothioamide
2a–2c or N-phenyl-β-D-pyranosyl hydrazine car-
bothioamide 3a–3 attacks on the carbon triplet bond
of acetylenic ester dimethylacetylenedicarboxylate,
and diethylacetylenedicarboxylate, or methyl bro-
mide of 2,4ꢀ-dibromoacetophenone, which are prone
to nucleophilic attack. Then cyclization proceeds on
to the esteric (CO2R) or carbonyl (CO) functional
groups to give products 4a–c and 5a–f in good yield
(Schemes 1 and 2).
The H NMR spectrum of 5a in DMSO showed
two multiplets for the sugar ring CH and CH2 pro-
tons at δ = 3.38–3.65 and 3.00–3.25 ppm, a methoxy
at δ = 3.72 ppm, hydroxyl groups at δ = 4.21–5.02
ppm, one doublet for NH at δ = 6.66 ppm, and
olefinic protons at δ = 6.82 ppm, along with one
doublet at δ = 7.00 ppm and two triplets at δ =
7.22 and 7.41 ppm for the aromatic protons. The
13C NMR spectrum of 5a showed 12 signals, which
are in agreement with the proposed structure. Par-
tial assignments of these resonances are given in the
Experimental section. The 1H and 13C NMR spectra
5b–f are similar to those for 5a, except for the es-
ter moiety, which exhibits characteristic signals at
appropriate chemical shifts.
On the basis of well-established chemistry of
electrophilic acetylenes, it is reasonable to assume
that compound 5 results from the initial con-
jugate addition of the sulfur atom of 3 to the
acetylenic ester. Subsequently, the ester group of this
intermediate is attacked by the amino moiety to yield
5 with the elimination of ROH.
To extend the study to other thiazole deriva-
tives, 3-phenyl-2-(β-D-galactopyranosyl) hydrazono-
thiazolidine-4-one was synthesized according to
the synthetic pathway shown in Scheme 3. The
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Darehkordi, Ramezani, and Ranjbar-Karimi
SCHEME 2 Synthesis of 4-oxothiazolidin-5-ylidene derivatives.
reaction of compound 3c with ethylbromoac-
etate led to the intermediate 3cꢀ (Scheme 3),
which, by a further intermolecular cyclization,
gave the corresponding 3-phenyl-2-(β-D-galacto-
pyranosyl)hydrazonothiazolidine-4-one 6 in quanti-
tative yield. The IR and 1H and 13C NMR spectra are
in agreement with the proposed structure.
at δ = 32.69 ppm (CH2 thiazolidine ring), δ = 165.03
ppm (imino group), and δ = 172.45 (carbonyl group),
confirming that the intermolecular cyclization had
occurred.
CONCLUSIONS
In summary, we described here a straightfor-
ward synthesis of β-D-gluco-, galacto-, and
mannopyranosylthiazoles, thiazolidinones, and
pyranosylthiazlidin-4-ones derivatives based on
the condensation of α-halocarbonyl compounds or
dialkylacetylenedicarboxylate with unprotected β-D-
pyranosylhydrazinecarbothioamide and N-phenyl-
β-D-pyranosyl hydrazine carbothioamide. This
method allowed us to prepare glucose, galactose,
IR spectra of 6 showed bands at νmax = 1569
cm−1 (C N), 1640, 1718 cm−1 (C O), and 3300–
1
3510 cm−1 (NH, OH). In the H NMR spectra of 6,
one singlet and a doublet signal observed at δ = 4.19
ppm (methylene protons, CH2 thiazolidine ring) and
7.57 ppm (NH proton) are in good agreement with
the values expected for these protons upon compar-
ison with similar compounds [26]. In the 13C NMR
spectra of compound 6, the signals were observed
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Synthesis of New Gluco-, Galacto-, and Mannopyranosylthiazoles, Thiazolidinones and Pyranosylthiazlidin-4-ones
5
SCHEME 3 Synthesis of 3-phenyl-2-(β-D-galactopyranosyl)hydrazonothiazolidin-4-one.
and maltose derivatives bearing C-linked to
thiazoles, thiazolidinones, and pyranosylthiazlidin-
4-ones rings. These compounds can be potentially
biological active.
and spots were developed using iodine vapors and
ultraviolet light as visualizing agents.
General Procedure for Synthesis of
4-Bromothiazol-2-ylidene Derivatives (4a–c)
EXPERIMENTAL
A
solution of β-D-pyranosylhydrazinecarbothio-
Chemicals and solvents such as EtOAC, EtOH, DMF,
and MeOH were obtained from Merck Chemical Co
(Merck Chemical Co. representative in Tehran (kimi-
aexir), Iran) and used without further purification.
Sugar thiosemicarbazone derivatives were prepared
according to a known procedure [18, 19]. Melting
points were determined on a Melt-Temp II melt-
ing point apparatus and are uncorrected. IR spectra
were obtained on a Matson-1000 FT-IR spectrom-
eter. Peaks are reported in wavenumbers (cm−1).
All of the NMR spectra were recorded on a Bruker
model DRX-500 AVANCE (1H: 500 MHz) (13C:
125 MHz) (Trabiatmodares University, Tehran, Iran)
and a Bruker model DRX-400 AVANCE (1H: 400
MHz) (13C: 100 MHz) (Kashan University, Kashan,
Iran) NMR spectrometer. Chemical shifts are re-
ported in parts per million (ppm) from tetram-
ethylsilane as an internal standard in DMSO-d6 as
a solvent. Assignments were confirmed with the
aid of two-dimensional techniques NMR (C H cor-
relation). Element analyses (C, H, and N) were
performed with a Heracus CHN-O-Rapid analyzer
(Trabiatmoalem University, Tehran, Iran). The pu-
rity of the compounds was checked by thin layer
chromatography (TLC) on Merck silica gel 60 F254
precoated sheets in n-hexane/ethyl acetate mixture,
amide (0.25 g, 1 mmol) in 8 mL of absolute ethanol
was stirred at ambient temperature for 20 min.
Then 2,4ꢀ-dibromoacetophenone (0.27 g, 1 mmol)
was added to this mixture and was refluxed for
12–18 h (the reaction was monitored by TLC 4:8
n-hexane/ethyl acetate). The mixture was cooled,
and the precipitate was filtered off and recrys-
tallized from EtOH, affording 4-bromothiazol-2-
ylidene derivatives (4a–c).
2-[N-(4-(4-Bromophenyl)-3H-thiazol-2-
ylidene]β-D-glucopyranoside (4a). mp
=
148◦C,
yield = 61%. Anal. Calcd. for C15H18BrN3O5S: C,
41.68; H, 4.20; N, 9.72; found: C, 41.57; H, 4.24;
N, 9.80. FT-IR (KBr) νmax (cm−1) 1629 (C N),
3250–3500 (NH, OH). 1H NMR (DMSO-d6, 500
MHz); δ (ppm): 2.96–2.98 (m, 1H, H-4ꢀ), 3.04 (t, J =
8.8, 1H, H-5ꢀ), 3.11 (t, J = 8.8, 1H, H-2ꢀ), 3.17–3.19
(m, 1H, H-3ꢀ), 3.52 (d, J = 11.35, 2H, H-6ꢀ), 3.91 (d,
J = 8.8, 1H, H-1ꢀ), 3.34–4.11 (m, 4H, OH), 7.29 (s,
1H, C CH), 7.56 (d, J = 8.3, 1H, NH), 7.62 (d, J =
8.5, 2H arom), 7.67–7.69 (d, J = 8.5, 2H arom), 7.75
(d, J = 8.5, 1H, NH). 13C NMR (DMSO-d6, 125.77
MHz); δ (ppm): 61.7 (1C, C-6ꢀ), 70.3(1C, C-4ꢀ), 71.0
(1C, C-5ꢀ), 77.3 (1C, C-2ꢀ), 77.8 (1C, C-3ꢀ), 90.1 (1C,
Heteroatom Chemistry DOI 10.1002/hc

6
Darehkordi, Ramezani, and Ranjbar-Karimi
C-1ꢀ), 104.2 (CH thiazole), 121.5 (C thiazole), 127.5,
127.8 (2CH arom), 131.4, 131.7 (2CH arom), 173.9
(C N).
acetate (5a). mp = 136–137◦C, Yield = 43%, Anal.
Calcd. for C18H21N3O8S: C, 49.20; H, 4.82; N, 9.56;
Found: C, 49.43; H, 5.02; N, 9.52. FT-IR (KBr); νmax
(cm−1): 1642 (C N), 1692, 1731 (C O), 3260–3500
1
2-[N-(4-(4-Bromophenyl)-3H-thiazol-2-ylidene]
β-D-mannopyranoside (4b). Pale brown solid,
mp = 185–188◦C, yield = 62%. Anal. Calcd. for
C15H18BrN3O5S: C, 41.68; H, 4.20; N, 9.72. Found:
C, 41.73; H, 4.18; N, 9.69. FT-IR (KBr); νmax
(cm−1): 1614 (C N), 3250–3500 (NH, OH). 1H NMR
(DMSO-d6, 400 MHz); δ (ppm): 2.72–3.30 (m, 4H,
OH), 3.65–3.69 (m, 2H, H-6ꢀ, OH), 4.08–4.11 (m, 1H,
H-5ꢀ), 4.57–4.89 (m, 4H, H-2ꢀ, H-3ꢀ, H-4ꢀ, H-1ꢀ), 7.21
(s, 1H CH), 7.32 (d, J = 8.3, 1H, NH), 7.58–7.87
(m, 4H, arom), 7.92 (d, J = 8.3, 1H, NH). 13C NMR
(DMSO-d6, 100 MHz); δ (ppm) 62.5 (1C, C-6ꢀ), 63.7
(1C, C-4ꢀ), 67.7 (1C, C-5ꢀ), 70.0 (1C, C-2ꢀ), 74.0 (1C,
C-3ꢀ), 78.2 (1C, C-1ꢀ), 103.3 ( CH), 120.0 (C C),
127.4, 127.4, 131.3, 131.4, 134.2 (arom), 174.1
(C N).
(NH, OH). H NMR (DMSO-d6, 400 MHz); δ (ppm):
3.38–3.65(m, 2H), 3.00–3.25 (m, 3H), 3.72(s, 3H,
CH3), 4.21–5.02 (m, 5H, H, OH), 6.66(d, J = 4,
1H, NH), 6.82(s, 1H, CH), 7.00 (d, J = 7.6, 2H,
arom), 7.22 (t, J = 8, 2H arom), 7.41(t, J = 8, 2H
arom). 13C NMR (DMSO-d6, 100 MHz); δ (ppm);
53.0(CH2), 61.8(1C, C-6ꢀ), 70.6 (1C, C-4ꢀ), 72.5 (1C,
C-5ꢀ), 77.3 (1C, C-2ꢀ), 78.7 (1C, C-3ꢀ), 79.6(1C, C-1ꢀ),
115.0( CH), 121.3 (C C), 128.4, 129.4, 129.9(arom).
Ethyl
2-((4-Oxo-2-(phenylimino)-3-(β-D-
glucopyranosyl-2-ylamino) thiazolidine-5-ylidene)
acetate (5b). Yellow light solid, mp = 131–135◦C,
yield = 48%. Anal. Calcd. for C19H23N3O8S: C, 50.32;
H, 5.11; N, 9.27; Found: C, 50.57; H, 5.17; N, 9.38.
FT-IR (KBr); νmax (cm−1): 1647 (C N), 1691, 1728
1
(C O), 3260–3500 (NH, OH). H NMR (DMSO-d6,
2-[N-(4-(4-Bromophenyl)-3H-thiazol-2-ylidene]
β-D-galactopyranoside (4c). Light brown solid,
mp = 148–156◦C, yield = 72%, Anal. Calcd. for
C15H18BrN3O5S: C, 41.68; H, 4.20; N, 9.72; Found:
C, 41.87; H, 4.30; N, 9.67. FT-IR (KBr); νmax
(cm−1): 1645 (C N), 3250–3400 (NH, OH). 1H NMR
(DMSO-d6, 400 MHz); δ (ppm): 3.37–4.31 (m, 11H,
7H, 4OH), 7.32 (s, 1H, CH), 7.43 (d, J = 6.4, 1H,
NH), 7.56–7.77 (m, 4H, arom), 7.65 (d, J = 8.8, 1H,
NH). 13C NMR (DMSO-d6, 100 MHz); δ (ppm): 61.0
(1C, C-6ꢀ), 63.4 (1C, C-2ꢀ), 68.6 (1C, C-4ꢀ), 74.4 (1C,
C-5ꢀ), 77.9 (1C, C-3ꢀ), 91.0 (1C, C-1ꢀ), 104.8 ( CH),
121.3 (C C), 128.2, 128.6, 128.8, 132.0, 132.3, 133.4
(6C, arom), 169.1(C N).
400 MHz); δ (pp): 1.18–1.22 (t, J = 6.8, 3H, CH3),
2.96–3.15 (m, 4H, H-4ꢀ, H-5ꢀ, H-2ꢀ, H-3ꢀ), 3.16–3.25
(m, 1H, H-1ꢀ), 3.50–3.68 (m, 2H, H-6ꢀ), 4.18 (q, J =
6.8, 2H, CH2), 4.21–5.02 (m, 7H, OH), 6.67 (NH),
6.79 (s, 1H, C CH), 7.00 (t, J = 8.0, 2H arom), 7.21
(t, J = 8.0, 1H arom), 7.40–7.50 (m, 3H, 2H arom,
NH) ppm. 13C NMR (DMSO-d6, 100 MHz); δ (ppm):
14.4 (CH3), 61.8 (CH2), 62.0 (1C, C-6ꢀ), 70.7 (1C,
C-4ꢀ), 72.5 (1C, C-5ꢀ), 77.3(1C, C-2ꢀ), 78.7 (1C, C-3ꢀ),
89.1 (1C, C-1ꢀ), 116.5 ( CH), 121.3 (C thiazole),
129.6, 129.9, 139.6, 147.6 (arom), 150.3 (C O ester),
162.4 (C O amide), 165.7 (C N).
Methyl
2-((4-Oxo-2-(phenylimino)-3-(β-D-
mannopyranosyl-2-ylamino)thiazolidine-5-ylidene)
acetate (5c). White solid, mp = 207–208◦C, Yield
= 57%, Anal. Calcd. for C18H21N3O8S C, 49.20;
H, 4.82; N, 9.56 Found: C, 49.63; H, 4.75; N, 9.62.
FT-IR (KBr); νmax (cm−1): 1594 (C N), 1647, 1711,
3300–3509 (NH, OH), 1H NMR (DMSO-d6, 400
MHz); δ (ppm): 3.40–3.70 (m, 4H), 3.80 (s, 3H, CH3),
4.08–5.43 (m, 2H, H, OH), 4.28–4.43 (m, 4H), 6.78
(s, 1H,=CH), 7.47–7.53 (m, 5H, arom), 7.62 (m, 1H,
NH). 13C NMR (DMSO-d6 100 MHz); δ (ppm): 53.1
(CH3), 64.3 (1C, C-6ꢀ), 69.8 (1C, C-4ꢀ), 70.5 (1C, C-5ꢀ),
71.1 (1C, C-2ꢀ), 71.5 (1C, C-3ꢀ), 115.3 ( CH), 128.6,
129.6, 134.7, 142.3(4C, arom), 160.4 (C C), 164.7
(C O ester), 166.4(C O amide), 166.7 (C N).
General Procedure for Synthesis of
4-Oxothiazolidine-5-ylidene Derivatives (5a–f)
A
solution
of
N-phenyl-β-D-pyranosylhydra-
mmol) in
zinecarbothioamide (0.32 g,
1
8 mL of absolute ethanol was well stirred at
ambient temperature for 20 min. Then dimethyl
acetylenedicarboxylate (0.12 mL, 1 mmol) or di-
ethyl acetylenedicarboxylate (0.16 mL, 1 mmol)
was added to this mixture and was refluxed for
8–12 h (the reaction was monitored by TLC 4:8
n-hexane/ethyl acetate). The mixture was cooled,
and the precipitate was filtered off and recrystallized
from methanol, affording the 4-oxothiazolidine-5-
ylidene derivatives (5a–c) as yellow light or white
crystals.
Ethyl
2-((4-Oxo-2-(phenylimino)-3-(β-D-
mannopyranosyl-2-ylamino)thiazolidine-5-ylidene)
acetate (5d). White solid, mp = 214–216◦C, Yield
= 58%, Anal. Calcd. for C19H23N3O8S C, 50.32; H,
5.11; N, 9.27; Found: C, 50.65; H, 5.24; N, 9.41.FT-IR
Methyl
2-((4-Oxo-2-(phenylimino)-3-(β-D-
glucopyranosyl- 2-ylamino)thiazolidine-5-ylidene)
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Synthesis of New Gluco-, Galacto-, and Mannopyranosylthiazoles, Thiazolidinones and Pyranosylthiazlidin-4-ones
7
(KBr); νmax (cm−1): 1537 (C N), 1645, 1717 (C O),
3337–3500 (NH, OH), 1H NMR (DMSO-d6, 500
MHz); δ (ppm): 1.27 (t, J = 6.8, 3H, CH3), 3.4–3.52
(m, 3H), 4.10–4.20 (q, J = 6.8, 2H, CH2), 4.27–5.32
(m, 7H, H, OH), 6.75 (s, 1H, C CH), 7.47–7.52 (m,
5H, arom), 7.60 (d, J = 4.0, 1H, NH). 13C NMR
(DMSO-d6, 125.77 MHz); δ (ppm): 14.5 (CH3), 61.9
(CH2), 64.7 (1C, C-6ꢀ), 69.8 (1C, C-4ꢀ), 70.5 (1C, C-5ꢀ),
71.1 (1C, C-2ꢀ), 71.5 (1C, C-3ꢀ), 115.6 ( CH), 128.6,
129.6, 134.7, 142.1 (arom), 160.5 (C C), 164.7 (C O
ester), 165.9 (C O amide), 166.6 (C N).
(0.05 mL, 0.5 mmol) was added to this mixture
and was refluxed for 24 h (the reaction was moni-
tored by TLC 4:8 n-hexane/ethyl acetate). The mix-
ture was cooled, and the precipitate was filtered
off and purified from water affording 3-phenyl-2-D-
galactopyranosylthiazolidine-4-one 6.
White solid, mp = 229–230◦C, yield = 44%. Anal.
Calcd. for C15H19N3O6S: C, 48.77; H, 5.18; N, 11.38.
Found: C, 48.39; H, 5.14; N, 11.55. FT-IR (KBr); νmax
(cm−1): 1569 (C N), 1640, 1718 (C O), 3300–3510
1
(NH, OH) cm−1. H NMR (DMSO-d6, 400 MHz); δ
(ppm): 3.44–3.48 (m, 2H, CH2), 3.67–4.05 (3H, 2H,
1OH), 3.67(d, J = 5.6, 1H), 4.05–4.86 (3H, OH),
4.14(d, J = 5.6, 1H), 4.22 (d, J = 0.6, 1H), 4.36 (d,
J = 0.6, 1H), 4.55 (d, J = 5.6, 1H), 7.33 (d, J = 7.2, 2H
arom), 7.44 (d, 1H arom), 7.48–7.49 (m, 2H arom),
7.57 (d, J = 6.0, 1H, NH). 13C NMR (DMSO-d6, 100
MHz); δ (ppm): 32.7(1C, CH2), 63.5 (1C, C-6ꢀ), 69.3
(1C, C-4ꢀ), 70.1 (1C, C-5ꢀ), 70.5 (1C, C-2ꢀ), 72.8 (1C,
C-3ꢀ), 79.6 (1C, C-1ꢀ), 128.7, 129.1, 129.3, 129.5, 135.5
(5C, arom), 165.0 (C N), 172.4 (C O).
Methyl
2-((4-Oxo-2-(phenylimino)-3-(β-D-
galactopyranosyl-2-ylamino)thiazolidine-5-ylidene)
acetate (5e). White solid, mp = 220–225◦C, yield
= 60%. Anal. Calcd. for C18H21N3O8S C, 49.20; H,
4.82; N, 9.56; Found: C, 4941; H, 4.72; N, 9.68. FT-IR
(KBr); νmax (cm−1): 1645 (C N), 1645, 1704 (C O),
3330–3496 (NH, OH). 1H NMR (DMSO-d6 400
MHz); δ (ppm): 3.37, 3.39 (m, 2H, H-4ꢀ, H-5ꢀ), 3.51,
3.52 (m, 2H), 3.65–4.63 (m, 2H, H, OH), 3.81 (s, 3H,
CH3), 4.15–4.17 (d, J = 6.8, 1H, H-2ꢀ), 4.41–4.43 (m,
2H), 4.97–4.99 (m, 1H), 6.79 (s, 1H, CH), 7.45–7.53
(m, 5H arom), 7.70 (d, J = 5.6, 1H, NH). 13C NMR
(DMSO-d6, 100 MHz); δ (ppm): 53.0 (CH3), 63.5 (1C,
C-6ꢀ), 69.4 (1C, C-2ꢀ), 70.1 (1C, C-4ꢀ), 70.7 (1C, C-5ꢀ),
72.8 (C-3ꢀ), 115.3 ( CH), 128.6, 129.6, 134.7, 142.2,
145.2 (5C, arom), 168.3 (C N).
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2-((4-Oxo-2-(phenylimino)-3-(β-D-
galactopyranosyl-2-ylamino)thiazolidine-5-ylidene)
acetate (5f). White solid, mp = 157–159◦C, yield
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128.6, 129.6, 134.6, 142.1 (5C, arom), 160.5(C C),
164.6 (C O ester), 165.9 (C O amide), 167.6 (C N).
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mL of absolute ethanol and calcium carbonate
(0.69 g, 0.5 mmol) was stirred at ambient tem-
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