Regioselective [3+2] cycloaddition of chalcones with a sugar azide: Easy access to 1-(5-deoxy-d-xylofuranos-5-yl)-4,5-disubstituted-1H-1,2,3-triazoles

Article abstract of DOI:10.1016/j.carres.2010.04.019

[3+2] Cycloaddition of 5-azido-5-deoxy-1,2-O-isopropylidene-α-d- xylofuranose with 1,3-diphenyl-prop-3-enones, followed by oxidation of the intermediate triazolines in a tandem manner, led to the regioselective formation of 4-benzoyl-1-(5-deoxy-1,2-O-isopropylidene-α-d-xylofuranos-5-yl)-5- phenyl-1H-1,2,3-triazoles in moderate to good yields.

Full text of DOI:10.1016/j.carres.2010.04.019

Carbohydrate Research 345 (2010) 1641–1648
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Regioselective [3+2] cycloaddition of chalcones with a sugar azide: easy access
to 1-(5-deoxy-D-xylofuranos-5-yl)-4,5-disubstituted-1H-1,2,3-triazoles
*
Nimisha Singh, S. K. Pandey, Rama P. Tripathi
Medicinal and Process Chemistry Division, Central Drug Research Institute, Lucknow 226 001, CSIR, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 March 2010
Received in revised form 15 April 2010
Accepted 21 April 2010
Available online 24 April 2010
[3+2] Cycloaddition of 5-azido-5-deoxy-1,2-O-isopropylidene-a-D-xylofuranose with 1,3-diphenyl-
prop-3-enones, followed by oxidation of the intermediate triazolines in a tandem manner, led to the
regioselective formation of 4-benzoyl-1-(5-deoxy-1,2-O-isopropylidene-a-D-xylofuranos-5-yl)-5-phenyl-
1H-1,2,3-triazoles in moderate to good yields.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
[3+2] Cycloaddition
Propenones
Chalcones
Sugar azide
1-(5-Deoxy-1,2-O-isopropylidene-a-D-
xylofuranos-4,5-disubstituted-1H-1,2,3-
triazoles
1. Introduction
Among various 1,2,3-triazoles, the preparation of 4- and/or 5-substi-
tuted 1H-1,2,3-triazoles has gained impetus in organic chemistry
where electron-deficient alkenes and different azides undergo
[3+2] cycloaddition followed by a subsequent elimination reaction
(Chart 1, A and B). However, in these methods the electron-deficient
alkene moieties always have an atom or group other than hydrogen
to be eliminated during the reaction. There are few reports where
azides undergo [3+2] cycloaddition to electron-deficient alkenes fol-
lowed by SET oxidation to give 1H-1,2,3-triazoles.23 The reaction of
alkenes or nitroalkenes with azides has been reported to give the
usual Michael addition product or nucleophilic substitution product
or other rearranged products.24,25 The propenone equivalents, the
polarized ketene S,S- and S,N-acetals, are reported to undergo cyclo-
addition with azides to give 1,2,3-triazoles by JunJappa’s group.26
[3+2] Cycloaddition of alkyl azides with enol ethers under sol-
vent-free conditions,27 and the thermal reaction of an aryl azide
with 1,2-dibenzoyl and 1,2-diacetyl ethylene28 have been reported
for the synthesis of substituted 1,2,3-triazoles. A similar reaction of
arylacrylyloxiranes with phenyl azide also resulted in epoxypropi-
nyl- and b-hydroxypropinyl triazoles.29 The cycloaddition product
formed during the reaction of chalcones with azides, followed by
oxidation to give 1,2,3-triazoles, has not been reported so far to
the best of our knowledge. In a continuation of our effort toward
the development of new antitubercular molecules, we have re-
cently reported the synthesis of 1,4-disubstituted 1,2,3-triazoles
as antitubercular agents.30,31 We were further interested to synthe-
size 1,4,5-trisubstituted 1,2,3-triazoles. Very recently Zhang and
Chang reported cycloaddition of azides to naphthoquinone
Owing to their broad spectrum applications in biochemical, phar-
maceutical, and material sciences, the 1H-1,2,3-triazoles are of key
importance in synthetic organic chemistry.1 They are commercially
used as anticorrosive agents,2 agrochemicals,3 photostabilizers, and
dyes.4 Several of these triazoles are drugs5 and have a wide range of
biological activities such as the inhibition of prostaglandin synthe-
sis,6 antimuscarimic activity, which reverses the neurochemical
deficiency in Alzheimer’s disease,7,8 inhibitory activity against
transforming growth factor b1 type1 receptor,9 anti-HIV-type I pro-
tease,10 HER2 kinase inhibitory activity in breast cancer,11 CB1 can-
nabinoid receptor antagonist activity,12 antimicrobial activity,13
antihyperglycemic activity,14 activity against lung cancer cells,15
galectin-1 and -3 inhibition,16 b-galactosidase inhibitory activity,17
probes of biological processes,18 glycogen phosphorylase inhibi-
tion,19,20 and antitubercular and antiparasitic activities.21 The
1,2,3-triazoles are commonly prepared by the Huisgen 1,3-dipolar
cycloaddition of azides with alkynes generally with electron-with-
drawing substituent(s) on both substrates. The click chemistry
developed by Sharpless and co-workers22 involving 1,3-dipolar
cycloaddition of azides with alkynes is one of the best methods to
develop 1,2,3-triazoles, in either aqueous or organic medium, and
the reaction has a variety of synthetic and biological applications.
* Corresponding author. Tel.: +91 522 2612411 418x4462; fax: +91 522 2623405/
2623938/2629504.
E-mail addresses: rpt.cdri@gmail.com, rp_tripathi@cdri.res.in (R.P. Tripathi).
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.04.019

1642
N. Singh et al. / Carbohydrate Research 345 (2010) 1641–1648
O
O
N
N
NH
H
NO2
TMSN3
N
NaN3,/DMSO
R
R
N
Δ
Δ
N
H
R
R
O
O
O
O
H3CS
H3CS
SCH3
(A)
(B)
R= C6H5, CH3, 4-ClC6H4
O
O
O
O
N
N
N
NaN3/R-Br
N
R
N
+
Δ
N
R
O
O
(C)
Chart 1. Reaction of labile group bearing alkenes and electron deficient alkenes with azides.
(Chart 1), which upon oxidation results in 1H-1,2,3-triazoles.32
Keeping in mind the above-mentioned points, we were prompted
to realize that such cycloadditions of sugar azides with chalcones
would generate a library of 1H-1,2,3-triazoles suitable for antitu-
bercular evaluations.
of the nitrogen atom of the azide (A) directly linked to the carbon
(C-50) of sugar ring on the b-carbon of the propenone (B), then the
enol form (C) generated in this process again resumes to its keto
form which leads to an attack by the p-electrons of the C–C double
bond on the terminal nitrogen of the azide, followed by the oxida-
tion (D) to give the products (E). In the proposed reaction mecha-
nism, TBAHS assists the reaction by acting as a phase-transfer
catalyst and possibly by activating the C–C double bond by forming
a complex with the lone-pair electrons of the carbonyl oxygen
(Fig. 1).
2. Results and discussion
The cycloaddition of a chalcone with a sugar azide was optimized
by the reaction of one of the prototype chalcones, E-3-(4-bromophe-
nyl)-1-(4-fluorophenyl)propenone (1) with 5-azido-5-deoxy-1,2-O-
The 1,4,5-substitution pattern in the above-mentioned triazoles
is in agreement with the 2D-NOESY and HMBC spectra (Figs. 2a
and b) of a prototype compound (4) where interactions of the
methylene protons of the sugar moiety (H-50) were observed (d
4.55–4.50) with the ortho aromatic protons (d 7.38–7.35) of the
4-bromophenyl ring a substitution on the fifth position of the tria-
zole (Fig. 3). Peaks were assigned with the help of 2D-NOESY and
HMBC spectra of the compound (4), wherein an interaction was
observed among the aromatic protons of the same ring. To gain fur-
ther insight on the 3D aspects of the structure as elucidated by
NMR spectral data, a 3D model of compound 4 was subjected to
energy minimization using SYBYL 6.3. In consensus with the
NMR spectrum, the distance between the aromatic hydrogen of
the 4-bromophenyl group and the sugar methylene hydrogen (H-
50) was found to be around 2.8 Å. All the above-mentioned obser-
vations conclusively confirm that the 4-bromophenyl group is
adjacent to the sugar moiety.
isopropylidene-
experimental conditions (Table 1) to get the 5-(4-bromophenyl)-
1-(5-deoxy-1,2-O-isolpropylidene- -xylofuranos-5-yl)-4-(4-flu-
a-D
-xylofuranose (2)31 (Scheme 1) under different
a
-D
orobenzoyl)-1H-1,2,3-triazole (5, entry 3). DMF as the solvent and
tetrabutylammonium hydrogen sulfate (TBAHS) (20 mol %) as a cat-
alyst at 100 °C proved to be the optimum reaction conditions.
In order to determine the scope of the reaction of different chal-
cones as substrates in the above-mentioned regioselective [3+2]
cycloaddition reaction followed by in situ oxidation, several chal-
cones were reacted with the above-mentioned 5-azido-5-deoxy-
1,2-O-isopropylidene-
a-
D-xylofuranose (2) (Scheme 2) to get the
respective 4-benzoyl-1-(5-deoxy-1,2-O-isopropylidene-
a-D-xylo-
furanos-5-yl)-5-phenyl-1H-1,2,3-triazoles (3–15) in varying yields
(Table 2).
The versatility of this reaction was further explored by reacting
E-3-(4-benzoyl)-1-(5-chlorophenyl)propenone (16) with an aryl-
alkylazide (benzyl azide), generated in situ by the reaction of ben-
zyl bromide and sodium azide (Scheme 3) under the above-
mentioned experimental conditions. Interestingly, the reaction
led to the formation of the expected product 4-benzoyl-1-benzyl-
5-(4-chlorophenyl)-1H-1,2,3-triazole (17) in good yield. Moreover,
3. Conclusions
In conclusion, we have successfully carried out the regioselec-
tive [3+2] cycloaddition reaction of propenones with 5-azido-5-
the reaction did not succeed when propenone lacked an
a-H on the
deoxy-1,2-O-isopropylidene-
a-D-xylofuranose in the presence of
olefinic carbon (Scheme 4). In the reaction, the conjugation of
tetrabutylammonium hydrogen sulfate as a catalyst to give the
olefinic and carbonyl
p-electrons apparently facilitates the attack
4-benzoyl-1-(5-deoxy-1,2-O-isopropylidene-a-D-xylofuranos-5-
F
O
N3
+
O
O
Solvent, Catalyst
N
N
O
N
F
Br
O
HO
O
O
Br
O
HO
Scheme 1. Scheme for the optimization of reaction conditions.

N. Singh et al. / Carbohydrate Research 345 (2010) 1641–1648
1643
Table 1
Standardization of the reaction condition for [3+2] cycloaddition of chalcone with sugar azide
Entry
Solvent
Catalyst (20 mol %)
Temperature (°C)
Time (h)
Yield (%)
1
2
3
4
5
6
7
DMF
DMF
DMF
DMF
DMSO
CH3CN
H2O
TBAHS
TBAHS
TBAHS
TBAHS
TBAHS
TBAHS
TBAHS
TBAHS
TBAHS
TBAHS
TBAHS
25
50
80
24
24
24
24
36
36
36
36
36
36
36
24
0
0
50
90
80
30
0
100
100
100
100
100
100
100
100
100
8
EtOH
0
9a
8
Toluene
1,4 Dioxane
CCl4
50
50
0
10
11a
DMF
50
L
-Proline
12
13
14
DMF
DMF
DMF
TBAB
—
TBAHS
100
100
50
36
36
24
50
20
0
a
A number of other un-isolable products along with the required product were observed (TLC).
R1
O
N
N
N
O
3
O
N
O
TBAHS (20 mol%), DMF
100 °C, 24 h
+
R2
R1
O
O
O
HO
Chalcones
R2
O
3-12
1
2
HO
R
O
1
2
1
2
3.
4.
R = 4-F, R = 3-NO2; R = 4-Cl, R = 4-Br
5. R1 = 4-F, R2 = 4-Br; 6. R1 = -H, R2 = 4-Br
7. R1 = -H, R2 = -Cl; 8. R1 = 4-F, R2 = 4-Cl
9. R1 = -H, R2 = 3-NO2; 10. R1 = -H, R2 = - H
11. R1 = 4-Cl, R2 = 4-Cl; 12. R1 = 4-Cl, R2 = 3-NO2
N
N
N
O
O
O
HO
13-15
13. R = -H; 14. R = 4-F; 15 R = 4-Cl
Scheme 2. Synthesis of compounds 3–15.
yl)-5-phenyl-1H-1,2,3-triazoles in moderate to good yields. The
reaction is simple as it involves readily available propenones
and azides and also does not involve any special reagents or con-
ditions. Application of this reaction and the products obtained
are underway to get a library of biologically active compounds.
Table 2
Regioselective preparation of 4-benzoyl-1-(5-deoxy-1,2-O-isopropylidene-a-D-xylo-
furanos-5-yl)-5-phenyl-1H-1,2,3-triazoles by the reaction of different chalcones with
a sugar azide
Entry
Chalcones
Product
Yield (%)
4. Experimental
4.1. General methods
R1/R
R2
R2
R/R1
=
=
Commercially available reagent grade chemicals were used as
received. All reactions were followed by TLC on E. Merck Kieselgel
60 F254, with detection by UV light and/or spraying with 5% H2SO4
in EtOH, followed by heating. Column chromatography was
performed on silica gel (60–120 mesh, E. Merck). IR spectra were
recorded as thin films or in chloroform solution with a Perkin–
Elmer Spectrum RX-1 (4000–450 cmꢀ1) spectrophotometer. 1H
and 13C NMR spectra were recorded on a Bruker DRX-300 in CDCl3.
Chemical shift values are reported in parts per million (ppm) rela-
tive to SiMe4 as the internal reference, unless otherwise stated; s
(singlet), d (doublet), t (triplet), m (multiplet); J in hertz. ESI mass
spectra were determined with Quattro II (Micromass) instrument.
1
2
3
4
5
6
7
8
9
10
11
12
13
4-F
4-Cl
4-F
-H
-H
4-F
-H
3-NO2
4-Br
4-Br
4-Br
4-Cl
4-Cl
3-NO2
-H
4-Cl
3-NO2
—
—
—
3
4
5
6
7
69
89
90
83
65
63
83
80
81
74
87
87
83
8
9
-H
10
11
12
13
14
15
4-Cl
4-Cl
-H
4-F
4-Cl

1644
N. Singh et al. / Carbohydrate Research 345 (2010) 1641–1648
Br
O
TBAHS (20 mol%), DMF
N
N
O
N
+ NaN3
+
100 C, 24 hrs
°
Cl
16
17
Cl
Scheme 3. Scheme for the synthesis of 1-benzyl-4-benzoyl-5-(4-chlorophenyl)-1H-1,2,3-triazole.
O
N3
O
O
+
No reaction
O
HO
Scheme 4. Reaction of xylosyl azide with bis-chalcone having no hydrogen atom on the
a-carbon.
Ar1
Ar2
H
Ar1
Ar2
H
B
N
(SO4)2-
O
N
NBu4
N
δ
O
H
N
N
N
δ
Sugar
C
SO4 NBu4
Sugar
A
NBu HSO
-
4
4
Ar1
Ar1
H
N
Sugar
Sugar
H
N
Ar2
-H2
Ar2
N
N
N
O
N
O
D
E
Figure 1. Most plausible reaction mechanism.
Elemental analyses were performed on a Perkin–Elmer 2400 II ele-
mental analyzer.
H-arom), 7.89 (d, 1H, H-arom), 7.75 (m, 1H, H-arom), 7.20 (m, 2H,
H-arom), 5.95 (d, J1,2 3.51 Hz, 1H, H-1), 4.70 (m, 2H, CH2), 4.59 (m,
1H, H-2), 4.41 (m, 2H, H-4, H-3), 3.17 (br s, 1H, OH), 1.46 (s, 3H,
CH3), 1.30 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3 + CCl4) d 184.0
(C@O), 167.6, 164.2, 148.1, 143.5, 140.4, 136.5, 133.5, 133.4,
132.89, 132.85, 129.6, 127.6, 125.5, 124.9, 115.6, 115.3, 112.2,
104.9 (C-1), 85.2 (C-2), 79.0 (C-4), 74.6 (C-3). 46.7 (C-5), 26.8 (1C,
CH3, isopropyl), 26.2 (1C, CH3, isopropyl); ESIMS (positive ion):
m/z: 485 [M+H]+. Anal. Calcd for C23H21FN4O7: C, 57.02; H, 4.37;
N, 11.57. Found: C, 56.91; H, 4.55; N, 11.42.
4.2. 4-(Benzoyl)-1-(5-deoxy-1,2-O-isopropylidene-a-D-
xylofuranos-5-yl)-5-(phenyl)-1H-1,2,3-triazol: typical
procedure
5-Azido-5-deoxy-1,2-O-isopropylidene-a-D-xylofuranose (2, 1
mmol) and 1,3-diphenyl propenones (1 mmol) were dissolved in
1 mL of DMF by stirring at 100 °C. TBAHS (20 mol %) was added into
the reaction mixture, which was further stirred at 100 °C for 24 h.
The reaction progress was monitored by TLC. After completion of
the reaction, the mixture was diluted with water and extracted with
EtOAc (50 mL). The organic layer was washed with water
(3 ꢁ 30 mL) to remove DMF and TBAHS from the reaction mixture
then dried (anhyd Na2SO4) and evaporated under reduced pressure
to get a crude mass. The latter was chromatographed over silica
gel (60–120 mesh) using a gradient of 3.5:10 EtOAc–hexane as elu-
ent to afford the desired product. All the products were light-yellow
solids.
4.2.2. 5-(4-Bromophenyl)-4-(4-chlorobenzoyl)-1-(5-deoxy-1,2-
O-isopropylidene-
Mp 164–166 °C; Rf 0.5 (7:4 hexane–EtOAc); ½
MeOH); IR (KBr)
max 3429 (OH), 1637 (C@N), 1217, 770 (arom); 1H
a-D-xylofuranos-5-yl)-1H-1,2,3-triazole (4)
20:2
546
a
ꢂ
ꢀ112.6 (c 0.1,
m
NMR (300 MHz, CDCl3 + CCl4) d 8.31 (d, 1H, H-arom), 7.72 (d, 1H,
H-arom), 7.51 (d, 1H, H-arom), 7.38 (d, 1H, H-arom), 5.94 (d, J1,2
3.42 Hz, 1H, H-1), 4.65 (m, 2H, CH2), 4.55 (m, 1H, H-2), 4.46 (m,
1H, H-4), 4.29 (s, 1H, H-3), 3.15 (br s, 1H, OH), 1.48 (s, 3H, CH3),
1.33 (s, 3H, CH3). 13C NMR (75 MHz, CDCl3 + CCl4) d 184.1 (C@O),
143.2, 141.6, 139.8, 135.0, 132.2, 132.1, 131.4, 128.6, 125.2,
124.5, 112.0, 105.0 (C-1), 85.1 (C-2), 78.9 (C-4), 74.6 (C-3), 45.8
(C-5), 26.9 (1C, CH3, isopropyl), 26.2 (1C, CH3, isopropyl); ESIMS
(positive ion): m/z: 534 [M+H]+. Anal. Calcd for C23H21BrClN3O5:
C, 51.66; H, 3.96; N, 7.86. Found: C, 51.45; H, 4.19; N, 7.68.
4.2.1. 1-(5-Deoxy-1,2-O-isopropylidene-
a-D-xylofuranos-5-yl)-
4-(4-fluorobenzoyl)-5-(3-nitrophenyl)-1H-1,2,3-triazole (3)
23
546
Mp 147–149 °C; Rf 0.5 (7:4 hexane–EtOAc); ½
MeOH); IR (KBr)
max 3457 (OH), 1597 (C@N), 1224, 737 (arom); 1H
NMR (300 MHz, CDCl3 + CCl4) d 8.52 (d, 1H, H-arom), 8.39 (m, 3H,
a
ꢂ
ꢀ0.016 (c 0.1,
m

N. Singh et al. / Carbohydrate Research 345 (2010) 1641–1648
1645
Figure 2a. NOESY spectrum of compound (4).
4.2.3. 5-(4-Bromophenyl)-1-(5-deoxy-1,2-O-isopropylidene-
a
-
D
-
(1C, CH3, isopropyl); ESIMS (positive ion): m/z: 502 [M+H]+. Anal.
Calcd for C23H22BrN3O5: C, 55.21; H, 4.43; N, 8.40. Found: C,
55.38; H, 4.32; N, 8.69.
xylofuranos-5-yl)-4-(4-fluorobenzoyl)-1H-1,2,3-triazole (5)
21:3
546
Mp 167–169 °C; Rf 0.5 (7:4 hexane–EtOAc); ½
aꢂ
ꢀ170.18 (c
0.1, MeOH); IR (KBr) mmax 3422 (OH), 1638 (C@N), 1216, 770
(arom); 1H NMR (300 MHz, CDCl3 + CCl4) d 8.42 (m, 2H, H-arom),
7.72 (d, 2H, H-arom), 7.39 (d, 2H, H-arom), 7.22 (t, 2H, H-arom),
5.94 (d, J1,2 3.51 Hz, 1H, H-1), 4.60 (m, 2H, CH2 and H-2), 4.53
(m, 1H, CH2), 4.46 (m, 1H, H-4), 4.29 (s, 1H, H-3), 1.48 (s, 3H,
CH3), 1.33 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3 + CCl4) d 184.2
(C@O), 143.7, 141.9, 133.9, 133.7, 132.2, 132.5, 131.9, 125.6,
124.2, 116.0, 115.6, 112.4, 105.4 (C-1), 85.5 (C-2), 79.3 (C-4), 75.0
(C-3), 46.2 (C-5), 27.3 (1C, CH3, isopropyl), 26.6 (1C, CH3, isopro-
pyl); ESIMS (positive ion): m/z: 518[M+H]+. Anal. Calcd for
4.2.5. 4-(Benzoyl)-5-(4-chlorophenyl)-1-(5-deoxy-1,2-O-
isopropylidene-
a-D-xylofuranos-5-yl)-1H-1,2,3-triazole (7)
26
Mp 131–133 °C; Rf 0.5 (7:4 hexane–EtOAc); ½
a
ꢂ
ꢀ43.3 (c 0.1,
546
MeOH); IR (KBr) mmax 3421 (OH), 1650 (C@N), 1217, 768 (arom);
1H NMR (300 MHz, CDCl3 + CCl4) d 8.26 (d, 2H, H-arom), 7.61 (m,
7H, H-arom), 5.90(s, 1H, H-1), 4.61 (m, 2H, CH2), 4.43 (m, 1H, H-
2), 4.31 (m, 1H, H-4), 4.16 (m, 1H, H-3), 3.5 (br s, 1H, OH), 1.45
(s, 3H, CH3), 1.38 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3 + CCl4) d
186.0 (C@O), 143.9, 141.7, 137.2, 137.1, 133.5, 131.7, 131.0,
129.5, 129.4, 128.6, 127.5, 124.5, 112.4, 105.4 (C-1), 85.5 (C-2),
79.4 (C-4), 74.9 (C-3), 46.2 (C-5), 27.3 (1C, CH3, isopropyl), 26.6
(1C, CH3, isopropyl); ESIMS (positive ion): m/z: 456 [M+H]+. Anal.
Calcd for C23H22ClN3O5: C, 60.59; H, 4.86; N, 9.22. Found C,
60.42; H, 5.02; N, 9.11.
C23H21BrFN3O5: C, 53.30; H, 4.08; N, 8.11. Found: C, 53.89; H,
4.79; N, 8.76.
4.2.4. 4-(Benzoyl)-5-(4-bromophenyl)-1-(5-deoxy-1,2-O-
isopropylidene-
a-D-xylofuranos-5-yl)-1H-1,2,3-triazole (6)
23
Mp 143–145 °C; Rf 0.5 (7:4 hexane–EtOAc); ½
aꢂ
ꢀ38.9 (c 0.1,
546
MeOH); IR (KBr): mmax 3428 (OH), 1639 (C@N), 1217, 771 (arom);
1H NMR (300 MHz, CDCl3 + CCl4) d 8.27 (d, 2H, H-arom), 7.69 (d,
2H, H-arom), 7.63 (m, 1H, H-arom), 7.52 (t, 2H, H-arom), 7.37 (d,
2H, H-arom), 5.92 (d, J1,2 3.39 Hz, 1H, H-1), 4.65 (m, 2H, CH2),
4.53 (m, 1H, H-2), 4.45 (m, 1H, H-4), 4.28 (m, 1H, H-3), 2.80 (br
s, 1H, OH), 1.46 (s, 3H, CH3), 1.32 (s, 3H, CH3); 13C NMR (75 MHz,
CDCl3 + CCl4) d 185.7 (C@O), 143.4, 141.3, 136.8, 133.1, 132.1,
131.5, 130.6, 128.2, 125.1, 124.6, 112.0, 105.0 (C-1), 85.1 (C-2),
79.0 (C-4), 74.5 (C-3), 45.7 (C-5), 26.9 (1C, CH3, isopropyl), 26.1
4.2.6. 5-(4-Chlorophenyl)-1-(5-deoxy-1,2-O-isopropylidene-a-D-
xylofuranos-5-yl)-4-(4-fluorobenzoyl)-1H-1,2,3-triazole (8)
24:4
546
Mp 139–141 °C; Rf 0.5 (7:4 hexane–EtOAc); ½
aꢂ
ꢀ0.31 (c 0.1,
MeOH); IR (KBr) mmax 3407 (C@O), 1639 (C@N), 1228, 784 (arom);
1H NMR (300 MHz, CDCl3 + CCl4) d 8.40 (m, 2H, H-arom), 7.54 (d,
2H, H-arom), 7.44 (d, 2H, H-arom), 7.20 (t, 3H, H-arom), 5.92 (d,
J1,2 3.42 Hz, 1H, H-1), 4.61 (m, 2H, CH2), 4.52 (m, 1H, H-2), 4.44
(m, 1H, H-4), 4.27 (m, 1H, H-3), 1.46 (s, 3H, CH3), 1.31 (s, 3H,
CH3). 13C NMR (75 MHz, CDCl3 + CCl4) d 183.8 (C@O), 143.3,

1646
N. Singh et al. / Carbohydrate Research 345 (2010) 1641–1648
Figure 2b. HMBC spectrum of compound (4).
Cl
arom), 8.30 (d, 2H, H-arom), 7.89 (d, 1H, H-arom), 7.75 (t, 1H, H-
arom), 7.61 (m, 1H, H-arom), 7.53 (m, 2H, H-arom), 5.96 (d, J1,2
3.27 Hz, 1H, H-1), 4.65 (m, 2H, CH2), 4.55 (m, 1H, H-2), 4.41 (m,
1H, H-4), 4.31 (m, 1H, H-3), 3.10 (br s, 1H, OH), 1.46 (s, 3H, CH3),
1.35 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3 + CCl4) d 185.6 (C@O),
148.2, 143.7, 140.2, 136.6, 136.4, 133.3, 130.7, 129.6, 128.2,
127.7, 125.4, 124.9, 112.2, 105.0 (C-1), 85.2 (C-2), 79.0 (C-4), 74.6
(C-3), 46.5 (C-5), 26.8(1C, CH3, isopropyl), 26.2(1C, CH3, isopropyl);
ESIMS (positive ion): m/z: 467[M+H]+; Anal. Calcd for C23H22N4O7:
C, 59.22; H, 4.75; N, 12.01. Found: C, 59.48; H, 4.54; N, 11.97.
N
N
O
N
H
H
O
4.2.8. 4-(Benzoyl)-1-(5-deoxy-1,2-O-isopropylidene-a-D-
xylofuranos-5-yl)-5-(phenyl)-1H-1,2,3-triazole (10)
O
CH3
CH3
23
546
H
Rf 0.5 (7:4 hexane–EtOAc); ½
a
ꢂ
ꢀ9.83 (c 0.1, MeOH); IR (KBr):
H
Br
mmax 3452 (C@O), 1653 (C@N), 1217, 765 (arom); 1H NMR
(300 MHz, CDCl3 + CCl4) d 7.84 (m, 10H, H-arom), 5.93 (d, J1,2
3.39 Hz, 1H, H-1), 4.64 (m, 2H, CH2), 4.50 (m, 1H, H-2), 4.26 (m,
2H, H-4, H-3), 1.46 (s, 3H, CH3), 1.37(s, 3H, CH3); ESIMS (positive
ion): m/z: 422[M+2H]+. Anal. Calcd for C23H23N3O5: C, 65.55; H,
5.50; N, 9.97. Found: C, 65.24; H, 5.37; N, 10.11.
O
HO
Figure 3. NOE interactions of methylene protons of the sugar moiety with phenyl
ring protons.
141.5, 136.8, 133.5, 133.3, 133.1, 131.3, 129.2, 124.1, 115.5, 115.2,
112.0, 105.0 (C-1), 85.1 (C-2), 78.9 (C-4), 74.6 (C-3), 45.8 (C-5), 26.8
(1C, CH3, isopropyl), 26.1 (1C, CH3, isopropyl); ESIMS (positive ion):
m/z: 474[M+H]+. Anal. Calcd for C23H21ClFN3O5: C, 58.29; H, 4.47;
N, 8.87. Found: C, 58.47; H, 4.33; N, 8.53.
4.2.9. 4-(4-Chlorobenzoyl)-5-(4-chlorophenyl)-1-(5-deoxy-1,2-
O-isopropylidene-
Mp 155–156 °C; Rf 0.5 (7:4 hexane–EtOAc); ½
MeOH); IR (KBr)
max 3409 (OH), 1655 (C@N), 1220, 772 (arom); 1H
a-D-xylofuranos-5-yl)-1H-1,2,3-triazole (11)
26
546
aꢂ
ꢀ53.39 (c 0.1,
m
NMR (300 MHz, CDCl3 + CCl4) d 8.29 (dd, 2H, H-arom), 7.54 (m, 6H,
H-arom), 5.93 (d, J1,2 3.54 Hz, 1H, H-1), 4.62 (m, 2H, CH2), 4.53 (m,
1H, H-2), 4.45 (m, 1H, H-4), 4.28 (m, 1H, H-3), 1.46 (s, 3H, CH3),
1.32 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3 + CCl4) d 184 (C@O),
143.2, 141.5, 139.8, 136.9, 135.1, 132.1, 131.2, 129.2, 128.9,
124.0, 112.0, 105.0 (C-1), 85.1 (C-2), 78.9 (C-4), 74.6 (C-3), 45.8
4.2.7. 4-(Benzoyl)-1-(5-deoxy-1,2-O-isopropylidene-
a-D-
xylofuranos-5-yl)-5-(3-nitrophenyl)-1H-1,2,3-triazole (9)
25:6
546
Mp 128–130 °C; Rf 0.5 (7:4 hexane–EtOAc); ½
MeOH); IR (KBr)
max 3409 (OH), 1662 (C@N), 1216, 768 (arom); 1H
NMR (300 MHz, CDCl3 + CCl4) d 8.51 (s, 1H, H-arom), 8.41 (d, 1H, H-
a
ꢂ
ꢀ9.17 (c 0.1,
m

N. Singh et al. / Carbohydrate Research 345 (2010) 1641–1648
1647
(C-5), 26.9 (1C, CH3, isopropyl), 26.1 (1C, CH3, isopropyl); ESIMS
4.2.14. 4-(Benzoyl)-1-benzyl-5-(4-chlorophenyl)-1H-1,2,3-
triazole (17)
(positive ion): m/z: 492[M+2H]+. Anal. Calcd for C23H21Cl2N3O5:
C, 56.34; H, 4.32; N, 8.57. Found: C, 56.21; H, 4.48; N, 8.43.
Rf 0.4 (7:2 hexane–EtOAc); mp 129–131 °C; IR (KBr):
m
max 3425,
1645 (C@N), 1450, 690 (arom); 1H NMR (300 MHz, CDCl3 + CCl4) d
4.2.10. 4-(4-Chlorobenzoyl)-1-(5-deoxy-1,2-O-isopropylidene-
8.35 (m, 2H, H-arom), 7.62 (m, 12H, H-arom), 5.47(s, 2H, CH2); 13
C
a
-
D
-xylofuranos-5-yl)-5-(3-nitrophenyl)-1H-1,2,3-triazole (12)
NMR (75 MHz, CDCl3 + CCl4) d 185.7 (C@O), 143.9, 140.6, 136.9,
136.4, 134.5, 133.0, 131.2, 130.8, 128.9, 128.6, 128.2, 127.5,
124.9, 52.0 (1C, CH2); ESIMS (positive ion): m/z: 374[M+H]+. Anal.
Calcd for C22H16ClN3O: C, 70.68; H, 4.31; N, 11.24. Found: C, 70.4;
H, 4.75; N, 11.09.
25:4
Mp 159–160 °C; Rf 0.5 (7:4 hexane–EtOAc); ½
aꢂ
+8.29 (c 0.1,
546
MeOH); IR (KBr) mmax 3408 (OH), 1657 (C@N), 1217, 767 (arom);
1H NMR (300 MHz, CDCl3 + CCl4) d 8.52 (d, 1H, H-arom), 8.51 (m,
1H, H-arom), 8.33 (m, 2H, H-arom), 7.90 (m, 1H, H-arom), 7.78
(m, 1H, H-arom), 7.75 (m, 2H, H-arom), 5.97 (d, J1,2 3.54 Hz, 1H,
H-1), 4.67 (m, 2H, CH2), 4.57 (m, 1H, H-2), 4.40 (m, 1H, H-4),
4.32 (m, 1H, H-3), 1.48(s, 3H, CH3), 1.37 (s, 3H, CH3); 13C NMR
(75 MHz, CDCl3 + CCl4) d 184 (C@O), 148.2, 143.5, 140.4, 140.0,
136.4, 134.8, 132.1, 129.6, 128.6, 127.5, 125.4, 125.0, 112.3, 104.9
(C-1), 85.2 (C-2), 78.9 (C-4), 74.6 (C-3), 46.5 (C-5), 26.8 (1C, CH3,
isopropyl), 26.2(1C, CH3, isopropyl); ESIMS (positive ion): m/z:
501[M+H]+. Anal. Calcd for C23H21ClN4O7: C, 55.15; H, 4.23; N,
11.19. Found: C, 55.37; H, 4.01; N, 11.38.
Acknowledgments
This is CDRI Communication No. 7929. The authors thank DRDO
New Delhi, CSIR New Delhi and DBT New Delhi, for financial assis-
tance. Nimisha Singh and S.K. Pandey are thankful to CSIR New
Delhi for SRF and RA, respectively. The authors sincerely thank
Dr. Ravishankar and Mr. Guniyal SAIF Div., CDRI Lucknow, for pro-
viding and analyzing the NOESY and HMBC spectral data.
4.2.11. 4-(Benzoyl)-1-(5-deoxy-1,2-O-isopropylidene-
a-D-
Supplementary data
xylofuranos-5-yl)-5-(2-naphthyl)-1H-1,2,3-triazole (13)
25
546
Mp 170–171 °C. Rf 0.5 (7:4 hexane–EtOAc); ½
aꢂ
ꢀ47.94 (c 0.1,
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.carres.2010.04.019.
MeOH); IR (KBr)
m
max 3402 (OH), 1627 (C@N), 1216, 765 (arom); 1H
NMR (300 MHz, CDCl3 + CCl4) d 8.31 (d, 2H, H-arom), 8.02 (m, 4H,
H-arom), 7.62 (m, 6H, H-arom), 5.92 (d, J1,2 3.48 Hz, 1H, H-1), 4.67
(m, 1H, H-2), 4.59 (m, 3H, CH2 and H-4), 4.28 (s, 1H, H-3), 3.15 (br s,
1H, OH), 1.46 (s, 3H, CH3), 1.32 (s, 3H, CH3); 13C NMR (75 MHz,
CDCl3 + CCl4) d 186.1 (C@O), 144.0, 142.9, 137.3, 134.2, 133.4,
133.2, 131.0, 130.6, 129.1, 128.8, 128.6, 128.3, 128.0, 127.3,
126.8, 123.3, 112.3, 105.4 (C-1), 85.4 (C-2), 79.5 (C-4), 74.9 (C-3),
46.0 (C-5), 27.3 (1C, CH3, isopropyl), 26.6 (1C, CH3, isopropyl);
ESIMS (positive ion): m/z: 472[M+H]+. Anal. Calcd for
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4.2.12. 1-(5-Deoxy-1,2-O-isopropylidene-a-D-xylofuranos-5-yl)-
4-(4-fluorobenzoyl)-5-(2-naphthyl)-1H-1,2,3-triazole (14)
23
546
Mp 177–178 °C; Rf 0.5 (7:4 hexane–EtOAc); ½
aꢂ
ꢀ21.9 (c 0.1,
MeOH); IR (KBr) mmax 3396 (OH), 1651 (C@N), 1219, 770 (arom);
1H NMR (300 MHz, CDCl3 + CCl4) d 8.40 (q, 2H, H-arom), 8.02 (m,
4H, H-arom), 7.62 (m, 3H, H-arom), 7.19 (t, 2H, H-arom), 5.939
(d, J1,2 2.28 Hz, 1H, H-1), 4.68 (d, 1H, J1,2 3.72 Hz, H-2), 4.63 (m,
3H, CH2, H-4), 4.28 (s, 1H, H-3), 3.20 (br s, 1H, OH), 1.45 (s, 3H,
CH3), 1.31 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3 + CCl4) d 184.3
(C@O), 143.5, 142.7, 133.8, 133.4, 133.3, 132.8, 129.9, 128.8,
128.4, 127.9, 127.7, 127.0, 26.3, 122.9, 115.6, 115.3, 112.1, 105.0
(C-1), 85.0 (C-2), 79.0 (C-4), 74.6 (C-3), 45.8 (C-5), 26.8 (1C, CH3,
isopropyl), 26.1 (1C, CH3, isopropyl); ESIMS (positive ion): m/z:
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8.58. Found: C, 66.02; H, 4.59; N, 8.31.
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23
546
Mp 179–181 °C; Rf 0.5 (7:4 hexane–EtOAc); ½
aꢂ
ꢀ37.1 (c 0.1,
MeOH); IR (KBr) mmax 3408 (OH), 1646 (C@N), 1224, 777 (arom);
1H NMR (300 MHz, CDCl3 + CCl4) d 8.29 (m, 2H, H-arom), 8.01
(m, 4H, H-arom), 7.63 (m, 5H, H-arom), 5.92 (d, 1H, J1,2 3.51 Hz,
H-1), 4.66 (m, 3H, CH2, H-2, H-4), 3.45 (br s, 1H, OH), 1.45 (s, 3H,
CH3), 1.31 (s, 3H, CH3); 13C NMR (75 MHz, CDCl3 + CCl4) d 183.4
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128.5, 128.4, 127.9, 127.6, 127.0, 126.3, 122.8, 112.0, 105.0 (C-1),
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pyl), 26.2 (1C, CH3, isopropyl); ESIMS (positive ion): m/z:
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