Synthesis and biological evaluation of novel 2-(4-O-β-D- glucosidoxyphenyl)-4,5-disubstituted imidazoles

Article abstract of DOI:10.1002/jhet.433

A series of 2-(4-hydroxyphenyl)-4,5-disubstituted imidazoles (1a-e) prepared from α-diketones, ammonium acetate, and p-hydroxybenzaldehyde, which were glucosylated by using α-acetobromoglucose to form 2-(4-O-β-D-2,3,4,6-tetra-O-acetyl-glucosidoxyphenyl)-4

Full text of DOI:10.1002/jhet.433

July 2010
Synthesis and Biological Evaluation of Novel 2-(4-O-b-D-
Glucosidoxyphenyl)-4,5-disubstituted Imidazoles
903
V. S. Taile,a* K. M. Hatzade,a,b P. K. Gaidhane,a and V. N. Inglea
aDepartment of Chemistry, Organic Research Laboratory-1, Rashtrasant Tukadoji Maharaj Nagpur
University, Nagpur-440 033, India
bDepartment of Chemistry, D. B. Science College, Gondia-441 614, Maharashtra, India
*E-mail: vijaytaile@gmail.com
Received December 16, 2009
DOI 10.1002/jhet.433
Published online 17 June 2010 in Wiley InterScience (www.interscience.wiley.com).
A series of 2-(4-hydroxyphenyl)-4,5-disubstituted imidazoles (1a–e) prepared from a-diketones, am-
monium acetate, and p-hydroxybenzaldehyde, which were glucosylated by using a-acetobromoglucose
to form 2-(4-O-b-D-2,3,4,6-tetra-O-acetyl-glucosidoxyphenyl)-4,5-disubstituted imidazoles (2a–e) which
on catalytic deacetylation with CH3ONa in methanol afforded the title compound 2-(4-O-b-D-glucosidox-
yphenyl)-4,5-disubstituted imidazoles (3a–e). Compounds were characterized by elemental analysis and
by instrumental technique, similarly the title compounds were investigated for antimicrobial and antifun-
gal activity.
J. Heterocyclic Chem., 47, 903 (2010).
INTRODUCTION
RESULTS AND DISCUSSION
In continuation of our work [1] with imidazole ring
which were very important in living systems like vita-
min B12. Imidazole also forms a part of some impor-
tant compounds such as purine, adenine, xanthine, gua-
nine, co-enzyme-a. It is also distributed in essential
amino acid, e.g., 1-histidine. Imidazoles possess, vari-
ous biological activities, viz., antibacterial [2,3], anti-
fungal [4], anti-inflammatory [5], antihistaminic [6],
and hypertensive [7]. Glucoconjugate and the carbohy-
drate containing structure [8,9] exhibit a variety of bio-
logical and therapeutic properties [10]. As a result, the
formation of glucosidic linkage continues to be a domi-
nant theme in carbohydrate chemistry [11,12]. The
attached sugar molecules increase water solubility and
tissue penetration. In addition to acting as a modifier,
carbohydrate can induce biological activity. In view of
various biological activities of imidazoles and the im-
portance of glucose moiety in the metabolism, several
compounds containing imidazole and glucose moiety
have been synthesized. Herein, we reported the synthe-
sis of 2-(4-hydroxyphenyl)-4,5-disubstituted imidazoles
and 2-(4-O-b-D-glucosidoxyphenyl)-4, 5-disubstituted
imidazoles.
Our general synthetic route starts with the aglycon
synthesis 1 it was prepared by condensation between a-
diketones, p-hydroxybenzaldehyde, and ammonium ace-
tate in the acetic acid medium [13]. The series of these
aglycon prepared by changing substitutions at 4,5 posi-
tions (1a–e). The glucosylation is carried out by using
modified Koenigs-Knorr method [14] (Scheme 1).
The mechanism of O-glucosylation reaction gained
immense importance due to its stereo-and regeoselective na-
ture. Glucosylation of 2-(4-hydroxyphenyl)-4,5-disubstituted
imidazole with a-acetobromoglucose (ACBG) followed by
deacetylation leads to the desired O-glucoside with distereose-
lectivity in favors of b-anomer. O-Glucosylation takes place
via SN1 and SN2 mechanism. In the absence of heavy metal
salts or Lewis acid catalyst mostly follows SN2 mechanism
which mainly leads to b-anomer as the preferred product. In
contrast, the presence of Lewis acid catalyst follows SN1
mechanism and is less distereoselective and regioselective.
This leads to the formation of a- and b-anomers. An
ester protecting group on the 2-hydroxyl group of the
donor will lead to the neighboring group participation
during O-glucosylation reaction and only the 1,2-trans-
diaxial glucoside (b-anomer) is the preferred product.
C
V
2010 HeteroCorporation

904
V. S. Taile, K. M. Hatzade, P. K. Gaidhane, and V. N. Ingle
Vol 47
Scheme 1
Glucosylation of 2-(4-hydroxyphenyl)-4,5-disubstituted
imidazoles with acetobromoglucose (ACBG) followed
by deacetylation leads the desired O-glucoside FT-IR data
of the O-glucoside are in agreement with the assigned
Candida albicans by adopting cup plate diffusion
method. The zone of inhibition after 7 days at 37ꢀC was
compared with standard drugs gentamycin and clotrim-
azole (100 lg/mL).
1
structure. Anomeric configuration confirmed by H NMR
since the coupling constant of the compound 8.5 Hz was
observed between H-1 and H-2 proton. 13C NMR
spectrum, C-1 resonated downfield of the other glucosyl
carbon at d 100.26 consistent with the formation of O-b-
glucosides. SN2 mechanism for 1,2-trans glucoside
formation 1,2-dioxyacylcarbonium ion (Scheme 2).
EXPERIMENTAL
The melting points (mp) are taken by using open capillary
method and are uncorrected. The FT-IR spectra were recorded
on Perkin-Elmer spectrophotometer using KBr disc. The 1H
NMR spectra are recorded on Bruker DRX-300 (300 MHz FT-
NMR) instrument using DMSO-d6 as a solvent and TMS as
internal standard, and the chemical shift are expressed in d
ppm values. EI-MS were recorded by direct insertion tech-
nique with a Hitachi Perkin Elmer RMU 6D mass Spectropho-
tometer. Elemental analysis was determined by the FLASH
EA 1112 CHN analyzer, Thermo Finigin, Italy.
BIOLOGICAL ASSAY
Antibacterial activity. The compounds (3a–e) were
screened for their antibacterial activities against various
pathogenic bacteria Escherichia coli, Klebisilla aero-
gens, Staphyllococcus aureus, and Bacillus substilis by
the cup plate diffusion of 100 lg/mL by using standard
ciprofloxacin and sulphacetamide (100 lg/mL) for bac-
teria. The zone of inhibition after 24 h of incubation at
37ꢀC was compared with standard drugs (Table 1).
Antifungal activity. The compounds (3a–e) were
screened for antifungal activity tasted at 100 lg/mL
concentration in methanol against Aspergillus niger and
General procedure for 2-(4-hydroxyphenyl)-4,5-disubsti-
tuted imidazoles (1a–e). A mixture of 4-hydroxy benzalde-
hyde (5 mmol), a-diketones (5 mmol), ammonium acetate (10
mmol), and glacial acetic acid (50 mL) was refluxed for 2 h. It
was poured on to cold water (200 mL) and neutralized with
NH4OH. The solid obtained was filtered, washed with water,
and crystallized from alcohol.
2-(4-Hydroxyphenyl)-4,5-diphenyl imidazole (1a). Yield
1.4 g (75%), mp 260ꢀC, Rf ¼ 0.78, FT-IR spectrum showed
the 3569.4 (AOH, broad) due to the presence of free phenolic
hydroxyl group and 1608 (C¼¼N, str.), 3165.3–2793.3 cmꢁ1
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2010
Synthesis and Biological Evaluation of Novel 2-(4-O-b-D-Glucosidoxyphenyl)-
4,5-disubstituted Imidazoles
905
Scheme 2
(aromatic ring, str.), 1235.6 (CAO bend), 3466.6 (ANH); 1H
NMR: d 7.2–7.5 (m, 14H, ArAH), 6.8 (s, 1H, OH), 7.9 (1H,
ANH, D2O exchangeable) Anal. Calcd. for C21H26N2O (312):
C, 80.75; H, 5.16; N, 8.97; Found: C, 80.65; H, 5.11; N, 8.85.
2-(4-Hydroxyphenyl)-5-phenyl imidazole (1b). Yield 54%;
mp 175ꢀC (ethanol); Rf ¼ 0.70, FT-IR: 3510 (AOH, broad),
3345.5 (ANH), 1612 (C¼¼N, str.), 1218 (CAO bend), 3165.3–
2790.3 cmꢁ1 (aromatic ring, str.).1H NMR: d ¼ 6.8 (s, 1H,
OH), 10.2 (1H, ANH, exchangeable with D2O), 6.5–7.3 (m,
9H, aromatic). Anal. Calcd. for C15H12N2O (236): C, 76.25;
H, 5.12; N, 11.86; Found: C, 76.18; H, 5.20; N, 11.82.
2-(4-Hydroxyphenyl)-imidazole (1c). Yield 72%; mp
190ꢀC (ethanol); Rf ¼ 0.68, FT-IR: 3585 (AOH, broad),
3358.0 (ANH), 1618 (C¼¼N, str.), 1220 (CAO bend), 3105.5–
2788.0 cmꢁ1 (aromatic ring, str.).1H NMR: d ¼ 5.6 (s, 1H,
OH), 9.5 (1H, ANH, exchangeable with D2O), 6.2A7.4 (m,
4H, aromatic). Anal. Calcd. for C9H8N2O (160): C, 67.49; H,
5.03; N, 17.49; Found: C, 67.56; H, 5.10; N, 17.45.
2-(4-Hydroxyphenyl)-4,5-dimethyl imidazole (1d). Yield 62%;
mp 135ꢀC (ethanol); Rf ¼ 0.54, FT-IR: 3424 (AOH, broad),
3269.0 (ANH), 1614 (C¼¼N, str.), 1224 (CAO bend), 3015.5–
2712. cmꢁ1 (aromatic ring, str.). 1H NMR: d ¼ 5.5 (s, 1H,
OH), 9.4 (1H, ANH, exchangeable with D2O), 6.2–7.8 (m,
4H, aromatic). Anal. Calcd. for C11H12N2O (188): C, 70.19;
H, 6.43; N, 14.88; Found: C, 70.25; H, 6.40; N, 14.90.
2-(4-Hydroxyphenyl)-4,5-bis-(4-chlorophenyl)-imidazole
(1e). Yield 60%; mp 245ꢀC (ethanol); Rf ¼ 0.73, FT-IR: 3520
(AOH, broad), 3370.0 (ANH), 1624(C¼¼N, str.), 1222 (CAO
bend), 3085–2712 cmꢁ1 (aromatic ring, str.).1H NMR d ¼ 5.8
(s, 1H, OH), 8.5 (1H, ANH, exchangeable with D2O), 6.1–7.5
Table 1
Antimicrobial activity 4,5-diaryl-2-(4-o-b-D-glucosidoxyphenyl) imidazoles (3a-e).
Zone of inhibitiona (mm) (activity index)std
Antibacterial activity
Gram-positive
Gram-negative
Antifungal activity
Compd. No.b
S. aureus
B. substilis
E. coli
K. aerogens
C. albicans
A. niger
3a
3b
3c
3d
3e
Std. 1
Std. 2
19(0.55)c (0.61)d
25(0.73)c (0.80)d
30(0.88)c (0.96)d
22(0.64)c (0.70)d
16(0.47)c (0.51)d
34
25(0.86)c (0.96)d
17(0.58)c (0.65)d
19(0.65)c (0.73)d
14(0.48)c (0.53)d
20(0.68)c (0.76)d
29
18(0.51)c (0.62)d
26(0.74)c (0.89)d
22(0.62)c (0.75)d
16(0.45)c (0.55)d
19(0.54)c (0.65)d
35
19(0.83)c (0.90)d
16(0.72)c (0.76)d
20(0.90)c (0.95)d
14(0.63)c (0.66)d
18(0.81)c (0. 85)d
22
21(1.00)c (0.91)d
25(1.19)c (1.09)d
17(0.80)c (0.73)d
18(0.85)c (0.78)d
20(0.95)c (0.86)d
21
23(0.92)c (1.00)d
17(0.68)c (0.71)d
19(0.76)c (0.79)d
20(0.80)c (0.83)d
14(0.56)c (0.58)d
25
31
26
29
21
23
24
a Average zone of inhibition in mm.
b Concentration of test compounds and standard 100 lg/mL. (Activity index) ¼ Inhibition zone of the sample/inhibition zone of the standard.
c Activity index against std. 1.
d Activity index against std. 2.For antibacterial activity: Std. 1 ¼ Ciprofloxacin and Std. 2 ¼ Sulphacetamide, for antifungal activity: Std. 1 ¼ Gen-
tamycin and Std. 2 ¼ Clotrimazole.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

906
V. S. Taile, K. M. Hatzade, P. K. Gaidhane, and V. N. Ingle
Vol 47
(m, 12H, aromatic). Anal. Calcd. for C21H14Cl2N2O (380): C,
66.16; H, 3.70; N, 7.35; Found: C, 66.32; H, 3.76; N, 7.32.
General procedure for 2-(4-o-b-D-2,3,4,6-tetra-o-acetyl-
glucosidoxyphenyl)-4,5-disubstituted imidazoles (2a–e). A
solution of 3 g potassium salt of 4,5-disubstituted-2-(4-hydrox-
yphenyl)-imidazole in 10 mL of 5% methanolic KOH was
added drop wise to a solution of 5 g of a acetobromoglucose
in 20 mL of dry acetone. The resulting mixture was stirred at
0ꢀC for 2 h. The reaction was allowed to proceed for an addi-
tional 24 h and the solvent remove under reduced pressure.
The reaction was monitored by TLC, A brown syrupy mass of
4,5-disubstituted-2-(4-O-b-D-2,3,4,6-tetra-O-acetyl glucosidoxy-
phenyl)imidazoles were obtained.
General procedure for 2-(4-o-b-D-glucosidoxyphenyl)-4,5-
disubstituted imidazoles (3a–e). A solution of 4,5-disubsti-
tuted-2-(4-O-b-D-2,3,4,6-tetra-O-acetyl glucosidoxyphenyl) im-
idazole (2 g) in 25 mL of dry methanol was added 1.5 mL of
5% CH3ONa solution .The reaction mixture was kept at room
temperature for additional 24 h. It was neutralized with ion-
exchange resin (Amberlite IR 120, s.d. fine, Hþ form) filtered
and concentrated in vacuum to afford viscous, strongly hygro-
scopic brown colored syrupy.
2-(4-o-b-D-Glucosidoxyphenyl)-4,5-diphenyl imidazole
30
(3a). Yield 65%; [a]D ¼ ꢁ9.88 (c, 0.1, DMSO); brown sy-
rup; Rf ¼ 0.12; FT-IR: 3200–3391.7 (AOH, broad, stretching).
2361.9 (aromatic str.), 1073.7 (CAOAC), 1609.9 cmꢁ1
1
2-(4-o-b-D-2,3,4,6-Tetra-o-acetyl glucosidoxyphenyl)-4,5-di-
phenyl imidazole (2a). Yield 3.57 g (65%). Rf ¼ 0.28. The
compound was found to be optically active and the specific
(C¼¼N). H NMR: 6.8–7.7 Hz (H, ArAH), 10.5 (s, ANH), 4.8
(d, 1H, J1, 2 ¼ 8.5 Hz, 10H) anomeric proton, 3.9 (1H, 20H),
3.4 (dd, 1H, 30H), 3.7 (1H, 40H), 3.2 (1H, 50H). 13C NMR:
d115–128 (ArAC), sugar moiety: d 100.26 (s, C-10) anomeric
carbon, 81 (s, C-60), 77 (s, C-50), 72 (s, C-40), 70.5 (s, C-30),
62 (s, C-20). EI-MS the molecular ion peak were observed at
474 (M þ 1) (46%) base peak observed at 312 (100 %), 118
(10 %), 77 (08 %). Anal.Calcd. for C27H26N2O6 (474): C,
68.34; H, 5.52; N, 5.90; Found: C, 68.37; H, 5.50; N, 5.86.
2-(4-o-b-D-Glucosidoxyphenyl)-5-phenyl imidazole (3b). Yield
30
rotation [a]D in DMSO was found to be ꢁ8.12. FT-IR spec-
trum of the compound showed following characteristic bands at
vmax 3424 (ANH), 1607 (C¼¼N), and 1074 (CAO) cmꢁ1. The
characteristic band due to phenolic hydroxyl group (3300–3500
cmꢁ1) was absent and the band due to CAOAC which appear at
1231 cmꢁ1 confirms the formation of O-glucoside.1H NMR: 2.02,
1.95,1.97, 2.01 (s, 3H) (COCH3), 4.8 (d, 1H, anomeric proton),
6.4–7.1 (m, 14H, ArAH), 10.5 (s, 1H, ANH). Anal. Calcd. for
C35H34N2O10 (642): C, 65.41; H, 5.33; N, 4.36; Found: C, 65.35;
H, 5.30; N, 4.38.
30
58%; [a]D ¼ ꢁ15.20 (c, 0.1, DMSO); brown syrup; Rf ¼ 0.8;
FT-IR: 3300 (AOH, broad), 2718.1 cmꢁ1 (aromatic str.), 1079.2
(CAOAC), 1620.6 cmꢁ1 (C¼¼N). 1H NMR: 6.8–7.8 (m, 9H,
ArAH), 10.4 (s, 1H, ANH), 3.3 (1H,50H), 3.5 (1H,40H), 3.4
(1H,30H), 3.8 (1H,20H), 5.0 (dd, 1H, J1, 2 ¼ 8.8 Hz, 10H).13C
NMR: d115–128 (ArAC), sugar moiety: d108 (s, C-10) anomeric
carbon, 80 (s, C-60), 76 (s, C-50), 71.5 (s, C-40), 70.5 (s, C-30), 60
(s, C-20). EI-MS: 398 (M) (20%), 220 (58%) 116 (100%) base
peak, 105 (10%), 78(4%). Anal.Calcd. for C21H22N2O6 (398): C,
63.31; H, 5.57; N, 7.03; Found: C, 63.34; H, 5.50; N, 7.06.
2-(4-o-b-D-Glucosidoxyphenyl) imidazole (3c). Yield 60%;
2-(4-o-b-D-2,3,4,6-Tetra-o-acetyl glucosidoxyphenyl)-5-phe-
30
nyl imidazole (2b). Yield 72%; [a]D ¼ ꢁ12.56 (c, 0.1,
DMSO); brown syrup; Rf ¼ 0.12; FT-IR: 3420 (ANH), 2855
(glucosidic CH), 2420 (ArACH), 1610 (C¼¼N), 1089 (CAO),
1
and 1225 cmꢁ1 (CAOAC). H NMR: 2.02, 1.94, 1.97, 2.01 (s,
3H) (COCH3), 5.1 (d, 1H, anomeric proton), 6.2 ꢁ7.0 (m, 9H,
ArAH), 9.6 (s, 1H, ANH). Anal. Calcd. for C29H30N2O10
(566): C, 61.48; H, 5.34; N, 4.94; Found: C, 61.42; H, 5.30;
N, 4.93.
30
[a]D ¼ ꢁ5.22 (c, 0.1, DMSO); brown syrup; Rf ¼ 0.15; FT-
2-(4-o-b-D-2,3,4,6-Tetra-o-acetyl glucosidoxyphenyl) imid-
IR: 3400 (AOH, broad), 2818.1 (aromatic str.), 1088.2
(CAOAC) glucosidic linkage, 1624 cm-1 (C¼¼N). 1H NMR:
6.5–7.9 (m, ArAH), 11.4 (s, 1H,ANH), 3.2 (1H, 50H), 3.4 (1H,
40H), 3.5 (1H, 30H), 3.9 (1H, 20H), 5.5 (dd, 1H, J1, 2 ¼ 10.2
Hz, 10H) anomeric proton. 13C NMR: d116–130 (ArAC), sugar
moiety: d110 (s, C-10) anomeric carbon, 82 (s, C-60), 77 (s, C-
50), 72.5 (s, C-40), 71.5 (s, C-30), 63 (s, C-20). EI-MS: 322 (M)
(28 %), 160 (100 %) base peak 146 (15 %), 77 (4 %). Anal.-
Calcd. for C15H18N2O6 (322): C, 55.90; H, 5.63; N, 8.69;
Found: C, 55.88; H, 5.60; N, 8.65.
30
azole (2c). Yield 82%; [a]D ¼ ꢁ2.24 (c, 0.1, DMSO); brown
syrup; Rf ¼ 0.22; FT-IR: 3428 (ANH), 2828 (glucosidic CH),
2610 (ArACH), 1618 (C¼¼N), 1085 (CAO), and 1210 cmꢁ1
1
(CAOAC). H NMR: 2.02, 1.90, 1.96, 2.01 (s, 3H) (COCH3),
5.4 (d, 1H, anomeric proton), 6.0–7.3 (m, 4H, ArAH), 9.8 (s,
1H, ANH). Anal. Calcd. for C23H26N2O10 (490): C, 56.32; H,
5.34; N, 5.71; Found: C, 56.38; H, 5.32; N, 5.76.
2-(4-o-b-D-2,3,4,6-Tetra-o-acetyl glucosidoxyphenyl)-
30
4,5-dimethyl imidazole (2d). Yield 78%; [a]D ¼ ꢁ8.16 (c,
0.1, DMSO); brown syrup; Rf ¼ 0.21; FT-IR (KBr): 3430
(ANH), 2832(glucosidic CH), 2612(ArACH), 1625 (C¼¼N),
2-(4-o-b-D-Glucosidoxyphenyl)-4,5-dimethyl
imidazole
30
(3d). Yield 68%; [a]D ¼ ꢁ11.10 (c, 0.1, DMSO); brown sy-
rup; Rf ¼ 0.16; FT-IR: 3380 (AOH, broad), 2910 (aromatic
str.), 1085.0 (CAOAC) glucosidic linkage, 1630 cmꢁ1 (C¼¼N).
1H NMR: 6.0–7.4 (m, ArAH), 10.2 (s,1H,ANH), 3.0 (1H,50H),
1
1087 (CAO), and 1218 cmꢁ1 (CAOAC). H NMR: 2.00, 1.92,
1.98, 2.01 (s, 3H) (COCH3), 5.1 (d, 1H, anomeric proton),
6.2–6.9 (m, 4H, ArAH), 10.2 (s, 1H, ANH). Anal. Calcd. for
C25H30N2O10 (518): C, 57.91; H, 5.83; N, 5.40; Found: C,
57.95; H, 5.84; N, 5.42.
3.2 (1H,40H), 3.5 (1H,30H), 3.7 (1H,20H), 5.6 (dd, 1H, J1, 2
¼
9.8 Hz, 10H) anomeric proton.13C NMR: d120–136 (ArAC),
sugar moiety: d115 (s, C-10) anomeric carbon, 88 (s, C-60), 86
(s, C-50), 76 (s, C-40), 70. (s, C-30), 65 (s, C-20). EI-MS: 350
(M) (25 %), 170 (100 %) base peak 118 (12 %), 78 (8 %).
Anal.Calcd. for C17H22N2O6 (350): C, 58.28; H, 6.33; N, 8.00;
Found: C, 58.32; H, 6.36; N, 8.05.
2-(4-o-b-D-2,3,4,6-Tetra-o-acetyl glucosidoxyphenyl)- 4,5-
30
bis-(4-chlorophenyl) imidazole (2e). Yield 75%; [a]D
¼
ꢁ4.10 (c, 0.1, DMSO); brown syrup; Rf ¼ 0.28; FT-IR (KBr):
3440 (ANH), 2795 (glucosidic CH), 2610 (ArACH), 1620
(C¼¼N), 1090 (CAO), and 1215 cmꢁ1 (CAOAC). 1H NMR:
2.00, 1.94, 1.96, 2.02 (s, 3H) (COCH3), 5.5 (d, 1H, anomeric
proton), 6.2–6.8 (m, 12H, ArAH), 11.4 (s, 1H, ANH). Anal.
Calcd. for C35H32Cl2N2O10 (710): C, 59.08; H, 4.53; N, 3.94;
Found: C, 59.05; H, 4.56; N, 3.96.
2-(4-o-b-D-Glucosidoxyphenyl)-4,5-bis-(4-chlorophenyl) imid-
30
azole (3e). Yield 62%; [a]D ¼ ꢁ6.80 (c, 0.1, DMSO); brown
syrup; Rf ¼ 0.20; FT-IR: 3420 (AOH, broad), 3015 (aromatic
str.), 1088.0 (CAOAC) glucosidic linkage, 1630 cmꢁ1 (C¼¼N).
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2010
Synthesis and Biological Evaluation of Novel 2-(4-O-b-D-Glucosidoxyphenyl)-
4,5-disubstituted Imidazoles
907
1H NMR: 6.0–7.3 (m, ArAH), 10.5 (s, 1H,ANH), 3.0 (1H, 50H),
[3] Dickens, J. P.; Ellames, G. J.; Hare, N. J.; Lawson, K. R.;
McKay, W. R.; Mutters, A. P.; Myers, P. L.; Pope, A. M. S.; Upton,
R. M. J Med Chem 1991, 34, 2356.
3.4 (1H, 40H), 3.5 (1H, 30H), 3.8 (1H, 20H), 5.2(dd, 1H, J1, 2
¼
9.0 Hz, 10H) anomeric proton. 13C NMR: d114–136 (ArAC),
sugar moiety: d103 (s, C-10) anomeric carbon, 78 (s, C-60), 77
(s, C-50), 75 (s, C-40), 73 (s, C-30), 67 (s, C-20). EI-MS: 542 (M)
(32 %), 380 (10 %) 246 (100 %) base peak, 163 (24 %), 137 (12
%), 77 (32 %). Anal.Calcd. for C27H24Cl2N2O6 (542): C, 59.68;
H, 4.45; N, 5.16; Found: C, 59.72; H, 4.48; N, 5.15.
[4] Ogata, M.; Matsumoto, H.; Hamada, Y.; Takehara, M.;
Tawara, K. J Med Chem 1983, 26, 768.
[5] Bhatia, M.; Naithani, P. K.; Bhalla, T. N.; Saxena, A. K. J
Indian Chem Soc 1992, 60, 594.
[6] Rama Sarma, G. V. S.; Reddy, V. M. Indian J Heterocycl
Chem 1993, 3, 111.
[7] Carini, D. J.; Dunica, J. V.; Aldrich, P. E.; Chiu, A. T.;
Johnson, A. L.; Pierce, M. E.; Price, W. A.; Santella, J. B., III; Wells,
G. J.; Wexler, R. R.; Wong, P. C.; Yoo, S. E.; Pieter, B. M.; Timmer-
mans, W. M. J Med Chem 1991, 34, 2525.
Acknowledgments. The authors are thankful to the Director, So-
phisticated Analytical Instrument Facility (SAIF) Chandigarh,
IIT-Powai, Mumbai, for providing necessary spectral analysis, to
the Head Department of Chemistry for providing necessary labo-
ratory facilities, and to the Head Department of Pharmacy for the
biological activities.
[8] Dwek, R. A. Chem Rev 1996, 96, 683.
[9] Davis, B. G. J Chem Soc Perkin Trans 1 1999, 3215.
[10] McAuliffe, J. C.; Hundsgaul, O. Chem Ind 1997, 170.
[11] Gupta, A.; Sharma, R.; Prakash, L. J Indian Chem Soc
1994, 71, 635.
REFERENCES AND NOTES
[12] Huryn, D. M.; Okabe, M. Chem Rev 1992, 92, 1745.
[13] Steck, E. A.; Day, A. R. J Am Chem Soc 1943, 65,
452.
[1] Ingle, V. N.; Hatzade, K. M.; Taile, V. S.; Gaidhane, P. K.;
Kharche, S. T. J Carbohydr Chem 2007, 26, 107.
[2] Kondo, H.; Taguchi, M.; Inoue, Y.; Sakamoto, F.;
Tssukamoto, G. J Med Chem 1990, 33, 2012.
[14] Koenig, W.; Knorr, E. Chem Ber 1901, 34, 957.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet