Synthesis of 2-(sulfamoylphenyl)-4′-(iminoaryl/hetroaryl)-4- (4′′-hydroxyphenyl)-thiazoles and their O-glucosides

Article abstract of DOI:10.1002/jhet.713

In continuation of our work, we synthesized 2-(sulfamoylphenyl)-4′- amino-4-(4″-hydroxyphenyl)-thiazole (3a), which were reacted with various (aryl/hetroaryl) aldehyde to form 2-(sulfamoylphenyl)-4′-(iminoaryl/ hetroaryl)-4-(4″-hydroxyphenyl)-thiazoles (4

Full text of DOI:10.1002/jhet.713

1428
Synthesis of 2-(Sulfamoylphenyl)-40-(iminoaryl/hetroaryl)-4-
Vol 48
(400-hydroxyphenyl)-thiazoles and Their O-Glucosides
V. S. Taile,a* K. M. Hatzade,a,b and V. N. Inglea
aOrganic Research Laboratory-1, Department of Chemistry, Rashtrasant Tukadoji Maharaj Nagpur
University, Nagpur 440 033, Maharashtra, India
bDepartment of chemistry, D.B.Science College, Gondia 441 614, Maharashtra, India
*E-mail: vijaytaile@gmail.com
Received June 9, 2010
DOI 10.1002/jhet.713
Published online 23 August 2011 in Wiley Online Library (wileyonlinelibrary.com).
In continuation of our work, we synthesized 2-(sulfamoylphenyl)-40-amino-4-(400-hydroxyphenyl)-thia-
zole (3a), which were reacted with various (aryl/hetroaryl) aldehyde to form 2-(sulfamoylphenyl)-40-
(iminoaryl/hetroaryl)-4-(400-hydroxyphenyl)-thiazoles (4a–f). Glucosylation of compounds (4a–f) have
been done by using acetobromoglucose as a glucosyl donor to afford 2-(sulfamoylphenyl)-40-(iminoaryl/
hetroaryl)-4-(2,3,4,6-tetra-O-acetyl-400-O-b-D-glucosidoxyphenyl)-thiazoles (5a–f), further on deacetyla-
tion to produce 2-(sulfamoylphenyl)-40-(iminoaryl/hetroaryl)-4-(400-O-b-D-glucosidoxyphenyl)-thiazoles
1
(6a–f). The compounds are confirmed by FTIR, H-NMR, 13C-NMR, and ES-Mass spectral analysis.
J. Heterocyclic Chem., 48, 1428 (2011).
INTRODUCTION
RESULTS AND DISCUSSION
Thiazoles are important heterocycles with great
applicability in medicinal chemistry, and this core
structure can be found in various biological/medicinal
applications like antimicrobial, anti-inflammatory, anti-
tubercular, anthelmintic, sedative hypnotics, and antire-
troviral activity [1–10]. The presence of imino group
is mainly responsible for the potent biological activity
of many compounds. These imines constitute one of
the most active classes of compounds possessing
diversified biological applications [11–15]. The sulfon-
amide drugs were the first effective chemotherapeutic
agents to be used systematically for the prevention
and cure of bacterial infections in man. The main fea-
ture of these compounds lies in the high therapeutics
index and low toxicity. Sulfonamide posses various bi-
ological activity such as antifungal, antimalerial, anti-
diabetic, and anti-ischemic [16–20]. O-glucosides play
important role in the carbohydrate chemistry, mainly
it used as carrier of aglycon. O-Glycosides have vari-
ous biological activities like anti-inflammatory, anti-
fungal, anticancer, antiviral, and antitumor activity
[21–31].
Our research envisage starts with the synthesis of 2-
amino-4-(40-hydroxyphenyl)-thiazole (1a); it was pre-
pared from 4-hydroxyacetophenone, iodine, and thiourea
[39,40]. Infra-red spectrum of this compound shows
characteristic bands at 3487.8 (AOH), 3379.5 (ANH2),
3127.7 (aromatic compound stretching), 1600 (C¼¼C),
1H NMR 6.44 (s, 1H, Thiazole), 6.80–7.82 (m, 4H,
Ar-H), 4.82 (bs, 2H, NH2), 5.66 (s, 1H, OH), which
confirmed the 2-amino-4-(40-hydroxyphenyl)-thiazole. By
using these starting material, we synthesized 2-(sulfa-
moylphenyl)-40-acetamido-4-(400-hydroxyphenyl)-thiazole
(2a) from reaction between p-acetamidobenzenesulfonyl
chloride and 2-amino-4-(40-hydroxyphenyl)-thiazole in
aqueous medium. These on further acid hydrolysis form
2-(sulfamoylphenyl)-40-amino-4-(400-hydroxyphenyl)-thi-
azole (3a), which shows the following characteristic
bands 3441.0 (AOH, str.), 3340 (ANH2), 1643 (C¼¼N),
3126.4 (Aromatic, str.), 1362.1 (SO2 str. asymmetric),
1112.2 (SO2 str. symmetric), 689.3 (CAS, str.), 771.1
1
(CASAC, str.). H-NMR 3.81 (s, 1H,ANH), 4.65 (bs,
2H, NH2), 5.22 (s, 1H, OH), 6.56 (s, 1H, Thiazole),
6.76–7.74 (m, 8H, Ar-H) confirmed the formation of
(3a). Schiff base was prepared by using 2-(sulfamoyl-
phenyl)-40-amino-4-(400-hydroxyphenyl)-thiazole (3a) to
react with various substituted (aryl/hetroaryl) aldehyde
to afford our aglycon moiety, i.e., 2-(sulfamoylphenyl)-
40-(iminoaryl/hetroaryl)-4-(400-hydroxyphenyl)-thiazoles
So, continuation of our work [32–38] and keeping
view of the various biological activities, it was proposed
to synthesize new molecules containing thiazole, azome-
thine, O-glucoside, and sulfonamide moiety in one
frame-work.
C
V
2011 HeteroCorporation

November 2011
Synthesis of 2-(Sulfamoylphenyl)-40-(iminoaryl/hetroaryl)-
4-(400-hydroxyphenyl)-thiazoles and Their O-Glucosides
1429
Scheme 1. Synthetic route of 2-(sulfamoylphenyl)-40-((iminoaryl/hetroaryl))-4-(400-hydroxyphenyl)-thiazole (4a–f). (i) iodine, (ii) p-acetamidosulo-
fonylchloride, (iii) acid hydrolysis, (iv) (aryl/hetroaryl) aldehyde.
(4a–f) (Scheme 1). The infra-red spectrum of the com-
pound (4a) showed following characteristic bands at
3367.1(AOH), 3105.1 (ANH), aromatic stretching
observed at 3043.1, and 1634 (C¼¼N), 1335 (SO2 str.
asymmetric), 1126 (SO2 str. symmetric), 640 (CAS, str.),
759.1 (CASAC, str), and there is absence of secondary
amine group peak; H-NMR spectrum showed chemical
1
shift values and displayed signal due to aromatic protons
Scheme 2. Synthetic route of 2-(sulfamoylphenyl)-40-(iminoaryl/hetroaryl)-4-(400-O-b-D-glucosidoxyphenyl)-thiazoles (6a–f). (i) CH3OH, KOH, (ii)
acetone, a-acetobromoglucose, (iii) CH3ONa,CH3OH.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

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V. S. Taile, K. M. Hatzade, and V. N. Ingle
Vol 48
recorded on Micromass: Q-T of micro (YA-105). Elemental
analyses were determined by the FLASH EA 1112 CHN ana-
lyzer, Thermo Finigin, Italy.
multiplet at d ¼ 7.24–8.20 Hz (m, 13H, Ar-H), hydroxyl
group proton at d ¼4.88 Hz and d ¼ 3.2063 Hz (1H,
ANH, D2O exchangeable).
General procedure for the preparation of 2-amino-4-(40-
hydroxyphenyl)-thiazole (1a). A mixture of p-hydroxyaceto-
phenone (0.1 mol), thiourea (0.2 mol), and iodine (0.2 mol)
was heated on water bath for 18 h with occasional stirring and
then cooled. The residue titurated with ether to remove excess
of unreacted p-hydroxyacetophenone. It was then washed with
sodium thiosulfate to removed iodine impurity. The crude
product is dissolved in boiling water and filter hot. The titled
compound formed after neutralized with aqueous ammonia;
the white colored compound was formed which was crystal-
lized from ethanol to get pale yellow needles, Yield (57%),
m.p. 201ꢁC; The infra-red spectrum of the compound showed
3487.8 (AOH), 3379.5 (ANH2), 3127.7 (Ar-H), 1600
(C¼¼C),1273 (CAN). 1H-NMR 6.44 (s, 1H, Thiazole), 6.80–
7.82 (m, 4H, Ar-H), 4.82 (bs, 2H, NH2), 5.66 (s, 1H, OH).
Anal. Calcd. for C9H8N2OS (192.24): C, 56.23; H, 4.19; N,
14.97; S, 16.68; Found: C, 56.24; H, 4.17; N, 14.97; S, 16.69.
General procedure for the preparation of 2-(sulfamoyl-
phenyl)-40-acetamido-4-(400-hydroxyphenyl)-thiazole (2a). A
mixture of the crude p-acetamidobenzenesulfonyl chloride
(0.064 mol), 2-amino-4-(40-hydroxyphenyl)-thiazole (0.40
mol), and water (30 mL) was heated with shaking on water
bath for 30 min. The reaction mixture was cooled at room
temperature, and the solid suspension of sulfonamide was
obtained. The reaction mixture was acidified with dil. H2SO4.
A yellow-colored solid separated out. It was washed several
times with water, filtered and dried, yield 66%, m.p. 240ꢁC,
The infra-red spectrum of the compound showed 3440.2
(AOH), 3385.0 (ANH2), 3115.5 (Ar-H), 1622 (C¼¼C), 1270
Glucosylation of 2-(sulfamoylphenyl)-40-((iminoaryl/
hetroaryl))-4-(400-hydroxyphenyl)-thiazole (4a–f) with
acetobromoglucose (ACBG) followed by deacetylation
leads to the desired O-glucoside with distereoselectivity
in favor of b-anomer. An ester protecting group on the
2-hydroxyl group of the donor will lead to the neighbor-
ing group participation during O-glucosylation reaction,
only b-anomer is obtained. The glucosylation carried
out by using Koeing-Knorr method [41] started with the
preparation of acetobromoglucose from glucose pentace-
tate and red phosphorous, which is then reacted with
potassium salt of compounds (4a–f) to produce 2-(sulfa-
moylphenyl)-40-(iminoaryl/hetroaryl)-4-(2,3,4,6-tetra-O-
acetyl-400-O-b-D-glucosidoxyphenyl)-thiazoles (5a–f).
The infra-red spectrum of the compound (5a) shows
following characteristic bands at vmax. The secondary
amine group observed at 3330.5 cmꢀ1, and the aro-
matic ring stretching at 3120.5–2980.6, 1620.5(C¼¼N),
628 (CAS), 740 (CASAC, str.), 1310 (SO2 str. asym-
metric), 1115.4 (SO2 str. symmetric); the band due to
CAOAC that appears at 1180 cmꢀ1 confirms the for-
mation of O-glucoside. 1H-NMR also confirmed the
5a. Further deacetylation of compound (5a–g) produces
our title molecules i.e. 2-(sulfamoylphenyl)-40-(imi-
noaryl/hetroaryl)-4-(400-O-b-D-glucosidoxyphenyl)-thiazoles
(6a–f) (Scheme 2). Infra-red spectrum shows that 3405
(AOH, broad, stretching) was observed due to carbohy-
drate hydroxyl groups. In the spectrum, 1411.5 (SO2
asymmetric, str.), 924.3 (SO2 asymmetric, str.), and the
presence of band at 1050.3 (CAOAC) indicate the forma-
tion of glucosidic linkage, and the band at 1635.9 (C¼¼N)
1
(CAN); H-NMR 3.80 (s, 1H, ANH), 4.35 (bs, 2H, NH2), 5.46
(s, 1H, OH), 6.68 (s, 1H, Thiazole), 6.90–7.92 (m, 4H, Ar-H),
9.10 (s, 1H, NH); Anal. Calcd. for C17H15N3O4S2 (389.45): C,
52.43; H, 3.88; N, 10.79; S, 16.47; Found: C, 52.44; H, 3.88;
N, 10.80; S, 16.47.
General procedure for the preparation of 2-(sulfamoyl-
phenyl)-40-amino-4-(400-hydroxyphenyl)-thiazole (3a). A
mixture of 2-(sulfamoyl phenyl)-40-acetamido-4-(400-hydroxy-
phenyl)-thiazole (10 g), conc. HCl (10 mL), and water (50
mL) was refluxed until a clear solution was obtained (for about
1h). The clear solution was then cooled at room temperature.
It was made alkaline with NaHCO3 (10 g) and cooled in ice
bath. A yellow solid was obtained. It was washed with water,
filtered, and dried yield 6 g (67%). The compound was crystal-
lized with aqueous ethanol, m.p.110ꢁC. Infra-red shows the
following characteristic bands 3441.0 (AOH, str.) due to the
presence of free phenolic hydroxyl group, 3340 (ANH2), 1643
(C¼¼N), 3126.4 (Aromatic, str.), 1362.1 (SO2 str. asymmetric),
1112.2 (SO2 str. symmetric), 689.3 (CAS, str.), 771.1
(CASAC, str.); 1H-NMR: 3.81 (s, 1H,ANH), 4.65 (bs, 2H,
NH2), 5.22 (s, 1H, OH), 6.56 (s, 1H, Thiazole), 6.76–7.74 (m,
8H, Ar-H). Anal. Calcd. for C15H13N3O3S2 (347.41): C, 51.86;
H, 3.77; N, 12.10; S, 18.46; Found: C, 51.86; H, 3.78; N,
12.09; S, 18.48.
1
cmꢀ1 was also observed which confirmed the (6a); H-
NMR of the compound displayed the signal due to sugar
protons between d 3.25–3.54 ppm and aromatic ring pro-
ton between d 7.28–8.24 ppm. The b-glucosidic bond for-
mation was established by the appearance of doublet at d
¼ 5.85 ppm. ES-spectra of (6a) show m/z (% abundance):
627.5 (M, 10), 434 (base peak, 100), 313 (12), 237 (49),
160 (09), 91 (02). 13C-NMR spectrum, C-1 resonated
downfield of the other glucosyl carbon at d 101–105.0
consistent with the formation of O-b-glucosides.
EXPERIMENTAL RESULT
General remarks. The melting points (m.p.) are taken by
using open capillary method and are uncorrected. The FTIR
spectra were recorded by using the Perkin-Elmer spectropho-
tometer with KBr disc. The 1H-NMR spectra recorded on
Bruker DRX-300 (300MHz FT-NMR) instrument using
DMSO-d6 as a solvent and TMS as internal standard, and the
chemical shift is expressed in d ppm values. ES-MS were
General procedure for the preparation of 2-(sulfamoyl-
phenyl)-40-(iminoaryl/hetroaryl)-4-(400-hydroxyphenyl)-thia-
zoles (4a–f). The condensation of 2-(sulfamoyl phenyl)-40-
(amino phenyl)-4-(400-hydroxyphenyl)-thiazole (0.01 mol) and
substituted aldehyde (0.01 mol) in 250-mL round-bottom flask
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2011
Synthesis of 2-(Sulfamoylphenyl)-40-(iminoaryl/hetroaryl)-
4-(400-hydroxyphenyl)-thiazoles and Their O-Glucosides
1431
with alcohol as solvent. To this mixture, few drops of conc.
H2SO4 were added. The mixture was refluxed about 3–4 h or
up to TLC passed. It was cooled to obtain the solid, filtered
and dried. It was crystallized from ethanol. Similarly, the
entire compounds (4a–f) were prepared.
2-(Sulfamoylphenyl)-40-(iminobenzal)-4-(400-hydroxyphenyl)-
thiazole (4a) Yield (62%); m.p. 120ꢁC; FTIR spectra 3367.1
(AOH), 3105.1 (ANH), 3043.1 (aromatic str.), 1634 (C¼¼N),
1335 (SO2 str. asymmetric), 1126 (SO2 str. symmetric), 640
(CAS, str.), 759.1 (CASAC, str); 1H-NMR d: 4.88 (s, 1H,
OH), 3.20 (1H, ANH, D2O exchangeable), 6.66 (s, 1H, Thia-
zole), 7.24–8.20 (m, 13H, Ar-H), 9.2 (s, 1H ,imines); Anal.
Calcd. for C22H17N3O3S2 (435.52): C, 60.67; H, 3.93; N, 9.65;
S, 14.72; Found: C, 60.66; H, 3.93; N, 9.66; S, 14.71.
2-(Sulfamoylphenyl)-40-(imino-4-methoxybenzal)-4-(400-hydrox-
yphenyl)-thiazole (4b) Yield (73%); m.p.105ꢁC; FTIR spectrum
shows 3330.4 (AOH), 3138.5 (ANH), 3010.4 (aromatic str.),
1624 (C¼¼N), 1334 (SO2 str. asymmetric), 1121 (SO2 str. sym-
metric), 640 (CAS, str.), 762.4 (CASAC, str); 1H-NMR d:
3.42 (s, 3H, OCH3), 3.73 (1H, ANH, D2O exchangeable), 4.28
(s, 1H, OH), 6.51 (s, 1H, Thiazole), 6.70–7.52 (m, 12H, Ar-
H), 8.85 (s, 1H, imines); Anal. Calcd. for C22H16ClN3O3S2
(465.54): C, 59.34; H, 4.11; N, 9.03; S, 13.78; Found: C,
59.32; H, 4.10; N, 9.08; S, 13.79.
Anal. Calcd. for C20H15N3O4S2 (425.48): C, 56.46; H, 3.55;
N, 9.88; S, 15.07; Found: C, 56.47; H, 3.56; N, 9.85; S, 15.09.
General procedure for the preparation of 2-(sulfamoyl-
phenyl)-40-(iminoaryl/hetroaryl)-4-(2,3,4,6-tetra-O-acetyl-400-
O-b-D-glucosidoxyphenyl)-thiazoles (5a–f). A mixture of 3 g
of potassium salt of 2-(sulfamoyl phenyl)-40-(iminoaryl/
hetroaryl)-4-(400-hydroxyphenyl)-thiazole (4a–f) in 10 mL of
5% methanolic KOH was added drop wise to a solution of 5 g
of acetobromoglucose in 20-mL dry acetone. The resulting
mixture was stirred at 0ꢁC for 2 h. The reaction was allowed
to proceed for an additional 24 h, and the solvent removed
under pressure. The resulting brown syrup was dissolved in
CH3OH-CH2Cl2 (8:2) and chromatogram on 60–120 cm silica
gel. The reaction was monitored by TLC. The solvent was
evaporated to obtained a brown syrupy, 2-(sulfamoyl phenyl)-
40-(iminoaryl/hetroaryl)-4-(2,3,4,6-tetra-O-acetyl-400-O-b-D-glu-
cosidoxyphenyl)-thiazole (5a–f). Similarly, using this proce-
dure all the compound 2-(sulfamoyl phenyl)-40-(iminoaryl/
hetroaryl)-4-(2,3,4,6-tetra-O-acetyl-400-O-b-D-glucosidoxy-
phenyl)-thiazole (5a–f) were prepared.
2-(Sulfamoylphenyl)-40-(iminobenzal)-4-(2,3,4,6-tetra-O-ace-
tyl-400-O-b-D-glucosidoxyphenyl)-thiazole (5a) Yield 72%;
30
[a]D ¼ ꢀ14.18 (c, 0.1, DMSO); brown syrup; FTIR: 1310
(SO2 str. asymmetric), 1115.4 (SO2 str. Symmetric), 1180.0
(CAOAC), 1620.5 (C¼¼N), 740 (CASAC), 628.0 (CAS,
2-(Sulfamoylphenyl)-40-(imino-4-fluorobenzal)-4-(400-hydrox-
yphenyl)-thiazole (4c) Yield (72%); m.p. 170ꢁC; FTIR spec-
trum shows 3342.0 (AOH), 3125.4 (ANH), 3008.2 (aromatic
str.), 1630 (C¼¼N), 1338 (SO2 str. asymmetric), 1122 (SO2 str.
1
bend); H-NMR: 2.02, 2.04, 1.99, 2.03 (s, 3H) (COCH3), 3.98
(s, 1H, NH), 5.95 (d, 1H, anomeric proton), 6.44 (s, 1H, Thia-
zole), 6.53–7.62 (m, 13H, Ar-H), 8.85 (s, 1H, ACH¼¼N);
Anal. Calcd. for C36H35N3O12S (765.81): C, 56.46; H, 4.61;
N, 5.49; S, 8.37; Found: C, 56.47; H, 4.60; N, 5.50; S, 8.37.
2-(Sulfamoylphenyl)-40-(imino-4-methoxybenzal)-4-(2,3,4,6-
tetra-O-acetyl-400-O-b-D-glucosidoxyphenyl)-thiazole (5b) Yield
1
symmetric), 642 (CAS, str.), 761.0 (CASAC, str); H-NMR d:
4.62 (s, 1H, OH), 3.50 (1H, ANH, D2O exchangeable), 6.83
(s, 1H, Thiazole), 7.0–8.44 (m, 12H, Ar-H), 9.4 (s, 1H,
imines); Anal. Calcd. for C22H16FN3O3S2 (453.51): C, 58.26;
H, 3.56; F, 4.19; N, 9.27; S, 14.14; Found: C, 58.28; H, 3.56;
F,4.20; N, 9.26; S, 14.15.
30
66%; [a]D ¼ ꢀ11.56 (c, 0.1, DMSO); brown syrup; FTIR:
1312 (SO2 str. asymmetric), 1118.0 (SO2 str. Symmetric),
1178.5 (CAOAC), 1622.4 (C¼¼N), 742 (CASAC), 630.5
(CAS, bend); 1H-NMR: 2.01, 2.02, 1.99, 2.04 (s, 3H)
(COCH3), 3.6 (s, 3H, OCH3), 3.9 (s, 1H, NH), 6.2 (d, 1H,
anomeric proton), 6.8 (s, 1H, Thiazole), 6.9–7.8 (m, 12H, Ar-
H), 8.2 (s, 1H, ACH¼¼N); Anal. Calcd. for C37H37N3O13S2
(795.83): C, 55.84; H, 4.69; N, 5.28; S, 8.06; Found: C, 55.85;
H, 4.69; N, 5.30; S, 8.07.
2-(Sulfamoylphenyl)-40-(imino-3-indolyl)-4-(400-hydroxyphenyl)-
thiazole (4d) Yield (70%); m.p.156ꢁC; FTIR spectrum shows
3415.0 (AOH), 3345.7 (ANH), 3014.2 (aromatic str.), 1635
(C¼¼N), 1332 (SO2 str. asymmetric), 1124 (SO2 str. symmet-
1
ric), 640.6 (CAS, str.), 758.0 (CASAC, str); H-NMR d : 4.84
(s, 1H, OH), 3.83 (1H, ANH, D2O exchangeable), 6.67 (s, 1H,
Thiazole), 7.0–8.84 (m, 13H, Ar-H), 9.17 (s, 1H, imines),
10.55 (s, NH, indole); Anal. Calcd. for C24H18N4O3S2
(474.55): C, 60.74; H, 3.82; N, 11.81; S, 13.51; Found: C,
60.75; H, 3.84; N, 11.80; S, 13.51.
2-(Sulfamoylphenyl)-40-(imino-4-fluorobenzal)-4-(2,3,4,6-tetra-
O-acetyl-400-O-b-D-glucosidoxyphenyl)-thiazole (5c) Yield 74%;
30
[a]D ¼ ꢀ35.25 (c, 0.1, DMSO); brown syrup; FTIR: 1312
2-(Sulfamoylphenyl)-40-(imino-4-pyridyl)-4-(400-hydroxyphenyl)-
thiazole (4e) Yield (75%); m.p.178ꢁC; FTIR spectrum shows
3440.3 (AOH), 3375.0 (ANH), 3025.1 (aromatic str.), 1632
(C¼¼N), 1330 (SO2 str. asymmetric), 1126 (SO2 str. symmet-
(SO2 str. asymmetric), 1118.0 (SO2 str. Symmetric), 1177.7
(CAOAC), 1622.2 (C¼¼N), 742 (CASAC), 629.5 (CAS,
1
bend); H-NMR: 2.02, 1.99, 1.98, 2.05 (s, 3H) (COCH3), 3.66
(s, 1H, NH), 6.20 (d, 1H, anomeric proton), 6.85 (s, 1H, Thia-
zole), 6.93–7.91 (m, 12H, Ar-H), 8.52 (s, 1H, ACH¼¼N);
Anal. Calcd. for C36H34FN3O12S (783.8): C, 55.17; H, 4.37; F,
2.42; N, 5.36; S, 8.18; Found: C, 55.17; H, 4.36; F, 2.41; N,
5.35; S, 8.17.
1
ric), 635.8 (CAS, str.), 759.2 (CASAC, str); H-NMR d: 3.94
(1H, ANH, D2O exchangeable), 4.42 (s, 1H, OH), 6.82 (s, 1H,
Thiazole), 7.22–8.56 (m, 12H, Ar-H), 8.8 (s, 1H, imines);
Anal. Calcd. for C21H16N4O3S2 (436.51): C, 57.78; H, 3.69;
N, 12.84; S, 14.69; Found: C, 57.77; H, 3.69; N, 12.83; S,
14.69.
2-(Sulfamoylphenyl)-40-(imino-3-indolyl)-4-(2,3,4,6-tetra-O-
acetyl-400-O-b-D-glucosidoxyphenyl)-thiazole (5d) Yield 64%;
30
2-(Sulfamoylphenyl)-40-(imino-2-furyl)-4-(400-hydroxyphenyl)-
thiazole (4f) Yield (64%); m.p.165ꢁC; FTIR spectrum shows
3408.5 (AOH), 3342.2 (ANH), 3038.2 (aromatic str.), 1634
(C¼¼N), 1333 (SO2 str. asymmetric), 1129 (SO2 str. symmet-
[a]D ¼ ꢀ9.18 (c, 0.1, DMSO); brown syrup; FTIR: 1318
(SO2 str. asymmetric), 1116.0 (SO2 str. Symmetric), 1172.4
(CAOAC), 1624.1 (C¼¼N), 738.8 (CASAC), 627 (CAS,
1
bend); H-NMR: 1.98, 1.99, 2.06, 2.07 (s, 3H) (COCH3), 3.85
1
ric), 637.2 (CAS, str.), 762.3 (CASAC, str); H-NMR d: 3.85
(s, 1H, NH), 6.06 (d, 1H, anomeric proton), 6.60 (s, 1H, Thia-
zole), 6.80–7.75 (m, 13H, Ar-H), 7.92 (s, 1H, ACH¼¼N); 8.94
(s, 1H, NH); Anal. Calcd. for C38H34N4O12S2 (804.84): C,
(1H, ANH, D2O exchangeable), 4.8 (s, 1H, OH), 6.72 (s, 1H,
Thiazole), 6.92–7.41 (m, 11H, Ar-H), 7.95 (s, 1H, imines);
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V. S. Taile, K. M. Hatzade, and V. N. Ingle
Vol 48
56.71; H, 4.51; N, 6.96; S, 7.97; Found: C, 56.70; H, 4.50; N,
6.96; S, 7.97.
65.1. 56.4; EI-MS: 627 (M, base peak, 100), 465 (20), 310 (06),
275 (31), 244 (14), 175 (14), 145 (21), 95 (12), 78 (16); Anal.-
Calcd. for C29H29N3O9S2 (627.69): C, 55.49; H, 4.66; N, 6.69,
S, 10.22; Found: C, 55.47; H, 4.68; N, 6.70; S, 10.23.
2-(Sulfamoylphenyl)-40-(imino-4-pyridyl)-4-(2,3,4,6-tetra-O-
acetyl-400-O-b-D-glucosidoxyphenyl)-thiazole (5e) Yield 60%;
30
[a]D ¼ ꢀ16.46 (c, 0.1, DMSO); brown syrup; FTIR: 1312
2-(Sulfamoylphenyl)-40-(imino-4-fluorobenzal)-4-(400-O-b-D-
30
(SO2 str. asymmetric), 1112.4 (SO2 str. Symmetric), 1175.6
(CAOAC), 1625.2 (C¼¼N), 731.2 (CASAC), 626.8 (CAS,
glucosidoxyphenyl)-thiazole (6c) Yield 66%; [a]D ¼ ꢀ30.80
(c, 0.1, DMSO); brown syrup; FTIR: 3406.2 (AOH, broad,
stretching), 3020.1 (aromatic str.), 1642.8 (C¼¼N), 1055.1
(CAOAC), 1415.2 (SO2 asymmetric, str.), 924.8 (SO2 asym-
1
bend); H-NMR: 1.99, 2.06, 1.99, 2.05 (s, 3H) (COCH3), 4.04
(s, 1H, NH), 6.33 (d, 1H, anomeric proton), 6.82 (s, 1H, Thia-
zole), 7.10–8.25 (m, 12H, Ar-H), 8.77 (s, 1H, ACH¼¼N);
Anal. Calcd. for C35H34N4O12S2 (766.79): C, 54.82; H, 4.47;
N, 7.31; S, 8.36; Found: C, 54.80; H, 4.47; N, 7.30; S, 8.37.
2-(Sulfamoylphenyl)-40-(imino-2-furyl)-4-(2,3,4,6-tetra-O-ace-
tyl-400-O-b-D-glucosidoxyphenyl)-thiazole (5f) Yield 62%;
1
metric, str.), 630.3 (CAS, bend); H-NMR: 3.0 (1H, 50H), 3.1
(1H, 40H), 3.5 (1H, 30H), 3.3 (1H, 20H), 5.98 (dd, 1H, J1, 2
¼
8.1 Hz, 10H) anomeric proton, 6.48 (s, 1H, Thiazole), 6.52–
7.96 (m, 12H, Ar-H), 8.44 (s, 1H, ACH¼¼N); 13C-NMR: d
174.0, 163.1, 161.2, 156,3, 154.1, 146.3, 145.0, 142.3, 140.2,
133.9, 129.1, 128.4, 128.0, 127.7, 126.6, 126.3, 125.6, 124.6,
123.0, 122.9, 120.8, 118.5, 103.5, 100.1, 83.1, 76.5, 75.5, 65.7;
EI-MS: 615.6 (M, base peak, 100), 455 (28), 358 (34), 185
(22), 176 (21), 165 (12), 117 (18), 104 (12), 77 (15); Anal.-
Calcd. for C28H26FN3O8S2 (615.65): C, 54.63; H, 4.26; F,
3.06; N, 6.83, S, 10.42; Found: C, 54.64; H, 4.26; F, 3.08; N,
6.82; S, 10.43.
30
[a]D ¼ ꢀ18.77 (c, 0.1, DMSO); brown syrup; FTIR: 1322
(SO2 str. asymmetric), 1110.7 (SO2 str. Symmetric), 1177.8
(CAOAC), 1621.3 (C¼¼N), 728.6 (CASAC), 625.3 (CAS,
1
bend); H-NMR: 2.01, 1.98, 1.99, 2.06 (s, 3H) (COCH3), 3.99
(s, 1H, NH), 6.52 (d, 1H, anomeric proton), 6.70 (s, 1H, Thia-
zole), 7.02–8.30 (m, 11H, Ar-H), 8.52 (s, 1H, ACH¼¼N); Anal
Calcd. for C34H33N3O13S2 (755.77): C, 54.03; H, 4.40; N,
5.56; S, 8.49; Found: C, 54.03; H, 4.41; N, 5.55; S, 8.50.
General procedure for the preparation of 2-(sulfamoyl-
phenyl)-40-(iminoaryl/hetroaryl)-4-(400-O-b-D-glucosidoxyphenyl)-
thiazoles (6a–f). To the compound 2-(sulfamoyl phenyl)-40-
(iminoaryl/hetroaryl)-4-(2, 3, 4, 6-tetra-O-acetyl-400-O-b-D-glu-
cosidoxyphenyl)-thiazole (5a) 2 g in 25 mL of dry methanol
was added 1.5 mL of 5% CH3ONa solution. The reaction mix-
ture was kept at room temperature for additional 24 h. It was
neutralized with ion-exchanged resin (Amberlite IR-120, sd
fine, Hþ form), filtered and concentrated in vacuum to afford
viscous, strongly hygroscopic, brown colored syrupy com-
pounds. By similar way compounds (6a–f) were prepared.
2-(Sulfamoylphenyl)-40-(iminobenzal)-4-(400-O-b-D-glucosi-
2-(Sulfamoylphenyl)-40-(imino-3-indolyl)-4-(400-O-b-D-gluco-
30
sidoxyphenyl)-thiazole (6d) Yield 56%; [a]D ¼ ꢀ8.12 (c,
0.1, DMSO); brown syrup; FTIR: 3422.4 (AOH, broad,
stretching), 3028.4 (aromatic str.), 1636.2 (C¼¼N), 1058.2
(CAOAC), 1420.0 (SO2 asymmetric, str.), 920.2 (SO2 asym-
1
metric, str.), 634.1 (CAS, bend); H-NMR: 3.2 (1H, 50H), 3.0
(1H, 40H), 3.0 (1H, 30H), 3.4 (1H, 20H), 3.88 (1H, ANH, D2O
exchangeable), 6.02 (dd, 1H, J1, ¼ 8.9 Hz, 10H) anomeric
2
proton, 6.76 (s, 1H, Thiazole), 6.83–7.97 (m, 13H, Ar-H), 8.85
(s, 1H, ACH¼¼N), 9.95 (s, NH, indole); 13C-NMR: d 173.4,
161.0, 157.6, 153.2, 148.2, 143.0, 139.2, 138.4, 135.5, 130.4,
128.8, 128.6, 128.1, 127.5, 126.0, 125.2, 124.2, 123.5, 122.7,
122.4, 122.0, 120.6, 118.8, 104.2, 102.8, 100.7, 82.1, 77.4,
75.2, 65.2; EI-MS: 636.0 (M, base peak, 100), 475 (16), 357
(25), 190 (40), 170 (20), 163 (18), 117 (13), 75 (10); Anal.-
Calcd. for C30H28N4O8S2 (636.7): C, 56.59; H, 4.43; N, 8.80,
S, 10.07; Found: C, 56.62; H, 4.42; N, 8.82; S, 10.06.
30
doxyphenyl)-thiazole (6a) Yield 77%; [a]D ¼ ꢀ13.21 (c,
0.1, DMSO); brown syrup; FTIR: 3405 (AOH, broad, stretch-
ing), 2980.0 (aromatic str.), 1635.9 (C¼¼N), 1050.3 (CAOAC),
1411.5 (SO2 asymmetric, str.), 924.3 (SO2 asymmetric, str.),
1
628.4 (CAS, bend); H-NMR: 3.0 (1H, 50H), 3.1 (1H, 40H),
2-(Sulfamoylphenyl)-40-(imino-4-pyridyl)-4-(400-O-b-D-gluco-
30
3.5 (1H, 30H), 3.2 (1H, 20H), 5.85 (dd, 1H, J1, 2 ¼8.4 Hz, 10H)
anomeric proton, 7.28–8.24 (m, 13H, Ar-H), 7.70 (s, 1H, Thia-
zole), 8.60 (s, 1H,ACH¼¼N); 13C-NMR: d 175.0, 163.3,
157.5,156,0, 148.4, 145.5, 138.2, 133.6, 131.3, 129.4, 128.9,
128.6, 128.5, 127.0, 126.6, 125.6, 124.9, 122.9, 122.0, 121.0,
118.0, 105.4, 100.1, 90.6, 80.5, 76.1, 75.0, 65.4. EI-MS: 627.5
(M, 10), 434 (base peak, 100), 313 (12), 237(49), 160 (09), 91
(02); Anal.Calcd. for C28H27N3O8S (627.59): C, 55.49; H,
4.66; N, 6.69, S, 10.22; Found: C, 55.47; H, 4.66; N, 6.69; S,
10.23.
sidoxyphenyl)-thiazole (6e) Yield 65%; [a]D ¼ ꢀ11.24 (c,
0.1, DMSO); brown syrup; FTIR: 3402.6 (AOH, broad,
stretching), 3015.5 (aromatic str.), 1633.1 (C¼¼N), 1055.0
(CAOAC), 1418.0 (SO2 asymmetric, str.), 922.8 (SO2 asym-
1
metric, str.), 636.0 (CAS, bend); H-NMR: 3.0 (1H, 50H), 3.1
(1H, 40H), 3.2 (1H, 30H), 3.4 (1H, 20H), 3.92 (1H,ANH, D2O
exchangeable), 5.92 (dd, 1H, J1, ¼ 8.0 Hz, 10H) anomeric
2
proton, 6.60 (s, 1H, Thiazole), 6.72–7.82 (m, 12H, Ar-H), 7.95
(s, 1H,ACH¼¼N); 13C-NMR: d 174.5, 162.2, 157.3, 154.6,
148.0, 144.2, 138.3, 130.4, 128.2, 128.1, 127.6, 126.4, 125.3,
124.1, 121.3, 115.2, 114.5, 110.6, 103.1, 101.4, 100.8, 81.5,
77.7, 76.8, 75.5, 71.6, 65.0; EI-MS: 598.0 (M, 12), 435 (base
peak, 100 %), 330 (16), 240 (34), 162 (16), 136 (23), 77 (18);
Anal.Calcd. for C27H26N4O8S2 (598.65): C, 54.17; H, 4.38; N,
9.36, S, 10.71; Found: C, 54.16; H, 4.40; N, 9.38; S, 10.72.
2-(Sulfamoylphenyl)-40-(imino-2-furyl)-4-(400-O-b-D-glucosi-
2-(Sulfamoylphenyl)-40-(imino-4-methoxybenzal)-4-(400-O-
30
b-D-glucosidoxyphenyl)-thiazole (6b) Yield 69%; [a]D
¼
ꢀ10.24 (c, 0.1, DMSO); brown syrup; FTIR: 3484.6 (AOH,
broad, stretching), 3008.2 (aromatic str.), 1640.1 (C¼¼N),
1052.3 (CAOAC), 1414.0 (SO2 asymmetric, str.), 926.1 (SO2
1
asymmetric, str.), 631.2 (CAS, bend); H-NMR: 3.1 (1H, 50H),
30
3.3 (1H, 40H), 3.4 (1H, 30H), 3.5 (1H, 20H), 3.8 (s, 3H, OCH3),
6.11 (dd, 1H, J1, 2 ¼ 8.0 Hz, 10H) anomeric proton, 6.6 (s, 1H,
Thiazole), 6.88–8.72 (m, 12H, Ar-H), 8.8 (s, 1H, ACH¼¼N);
13C-NMR: d 173.0, 164.3, 160.5, 156.0, 153.0, 146.4, 145.3,
132.6, 131.4, 129.1, 128.4, 128.1, 127.2, 127.0, 126.7, 125.1,
124.4, 123.2, 122.4, 121.8, 119.5, 104.2, 100.5, 81.2, 76.4, 75.3,
doxyphenyl)-thiazole (6f) Yield 58%; [a]D ¼ ꢀ17.14 (c, 0.1,
DMSO); brown syrup; FTIR: 3388.8 (AOH, broad, stretching),
3081.0 (aromatic str.), 1631.0 (C¼¼N), 1055.3 (CAOAC),
1412.6 (SO2 asymmetric, str.), 932.5 (SO2 asymmetric, str.),
1
631.2 (CAS, bend); H-NMR: 3.0 (1H, 50H), 3.4 (1H, 40H),
3.2 (1H, 30H), 3.4 (1H, 20H), 6.05 (dd, 1H, J1, 2 ¼8.9 Hz, 10H)
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

November 2011
Synthesis of 2-(Sulfamoylphenyl)-40-(iminoaryl/hetroaryl)-
4-(400-hydroxyphenyl)-thiazoles and Their O-Glucosides
1433
[16] Mastrolorenzo, A.; Scozzafava, A.; Supuran, C. T. Eur J
Pharm Sci 2000, 11, 99.
anomeric proton, 6.65 (s, 1H, Thiazole), 7.10–8.34 (m, 11H,
Ar-H), 8.42 (s, 1H,-CH¼¼N). 13C-NMR: d 173.2, 158.2, 153,2,
149.3, 148.3, 146.2, 143.2, 140.4, 138.9, 131.4, 129.6, 128.3,
127.1, 126.2, 125.7, 124.6, 122.6, 122.2, 115.2, 114.2, 103.3,
100.5, 98.4, 83.5, 78.3, 75.4, 66.2. EI-MS: 587.2 (M, base
peak 100), 425 (28), 345 (30), 254 (24), 176 (11), 163 (21),
92 (08), 77 (14); Anal.Calcd. for C26H25N3O9S2 (587.62): C,
53.14; H, 4.29; N, 7.15, S, 10.91; Found: C, 53.16; H, 4.26;
N, 7.14; S, 10.93.
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Acknowledgments. The authors are thankful to the Director,
Sophisticated Analytical Instrument Facility (SAIF) Chandi-
garh for providing necessary spectral analysis, Head Depart-
ment of Chemistry for providing necessary laboratory
Facilities, and Head Department of Pharmacy for the biologi-
cal activities.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet