Benzotriazole-mediated facile synthesis of novel glycosyl tetrazole

Article abstract of DOI:10.1080/07328303.2011.652790

A facile, simple, and high-yielding synthetic protocol for novel glycosyl tetrazoles has been devised from different carbohydrate-containing amides using benzotriazole methodology under mild reaction condition.

Full text of DOI:10.1080/07328303.2011.652790

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Benzotriazole-Mediated Facile Synthesis
of Novel Glycosyl Tetrazole
Raju R. Kale a , Virendra Prasad a , Divya Kushwaha a & Vinod K.
Tiwari a
a Department of Chemistry, Centre of Advanced Study, Banaras
Hindu University, Varanasi, 221005, India
Available online: 07 Feb 2012
To cite this article: Raju R. Kale, Virendra Prasad, Divya Kushwaha & Vinod K. Tiwari (2012):
Benzotriazole-Mediated Facile Synthesis of Novel Glycosyl Tetrazole, Journal of Carbohydrate
Chemistry, 31:2, 130-142
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Journal of Carbohydrate Chemistry, 31:130–142, 2012
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Copyright Taylor & Francis Group, LLC
ISSN: 0732-8303 print / 1532-2327 online
DOI: 10.1080/07328303.2011.652790
Benzotriazole-Mediated Facile
Synthesis of Novel Glycosyl
Tetrazole
Raju R. Kale, Virendra Prasad, Divya Kushwaha,
and Vinod K. Tiwari
Department of Chemistry, Centre of Advanced Study, Banaras Hindu University,
Varanasi-221005, India
A facile, simple, and high-yielding synthetic protocol for novel glycosyl tetrazoles
has been devised from different carbohydrate-containing amides using benzotriazole
methodology under mild reaction condition.
Keywords Carboxamide; Imidoylbenzotrizole; Tetrazole; Cyclization
INTRODUCTION
Carbohydrate-containing molecules are known for their great medicinal
value.[1] Heterocycles coupled with the pendant sugar moiety through a C C
bond show a high chemotherapeutic potential,[2] represent a broad spectrum of
biological activities such as antitumor and antiviral activities, and have been
studied as building blocks in artificial DNA and RNA for various biochemical
applications.[3] They have also been used as promising activating catalysts for
phosphoramidites to facilitate the formation of N-acylphosphoramidate link-
ages through rapid condensation with carboxamides.[4] Carbohydrate coupled
with tetrazole heterocycle may occupy a pivotal position in medicinal chemistry
since several tetrazoles are known for their wide range of pharmacological ac-
tivities (Fig. 1). The tetrazolyl group consists of nonclassical isosteres of car-
boxylic acid and thus has been a suitable substitution in drug design in recent
years.[5] Tetrazole may serve as a substrate for N-glucuronidation of xenobi-
otics, which is an important pathway for the biological clearance of drugs.[6]
Received July 5, 2011; accepted December 13, 2011.
Address correspondence to Vinod K. Tiwari, Department of Chemistry, Centre of Ad-
vanced Study, Banaras Hindu University, Varanasi-221005, India. E-mail: vtiwari@
ucdavis.edu; tiwari chem@yahoo.co.in
130

Synthesis of Novel Glycosyl Tetrazole
131
Figure 1: Tetrazole-containing biologically active molecules.
Nohara et al. identified tetrazole N1 β-glucuronide in the urine stream of sev-
eral animals orally dosed with a chromone-derived tetrazole.[7] The majority of
tetrazolic acid–based drugs are of the biphenyl tetrazole motif, which are basi-
cally analogs of DuPont’s nonpeptidic selective angiotensin II receptor antago-
nist Losartan, a drug to treat hypertension.[8] A tetrazole-based nonpeptidyl
growth hormone secretagogue L-692,429, developed by Merck & Company,
provides an increased in vitro potency with an excellent oral absorption.[9]
Physicochemical properties including the bioavailability of the angiotensin II
receptor antagonist BMS-183920 may be improved even better than threefold
(from 11% to 37%) by N-“bioreversible” protection of the tetrazole with a pival-
oylisobutyl moiety.[10] Carbohydrate-containing tetrazole derivatives, for exam-
ple, 3ꢁ-(5-substituted-tetrazol-2-yl)-2,3ꢁ-dideoxythymidines, have been used in
drug development against viral infection.[11]
The common synthetic approaches for substituted triazole are based on
Huisgen’s 1,3-dipolar cycloaddition of azides with alkynes.[12a] These strate-
gies were further extended to achieve the regioselective synthesis of var-
ious substituted triazoles under the catalysis of Cu(I) or Ru-complex.[12b,c]
Although the synthesis of triazole skeleton has been well investigated in
recent years, surprisingly less attention has been paid to the synthesis of
the tetrazole ring. The synthesis of 5-substituted 1H-tetrazoles is known

R.R. Kale et al.
132
by I2 or silica-supported NaHSO4-catalyzed reaction of organic nitriles with
azide[13a] or treatment of nitrile with triethylammonium chloride in nitroben-
zene under microwave (MW) irradiation.[13b] Yb(OTf)3-catalyzed multicompo-
nent reaction of amines, NaN3, and triethyl orthoformate gave good yields of
1-substituted 1H-tetrazole.[13c] Shie et al. successfully applied [2 + 3] cycload-
dition reaction of nitriles, obtained in situ from primary alcohols or aldehy-
des, with dicyandiamide and NaN3 to get a similar tetrazole skeleton.[14a]
Katritzky et al. achieved 1,5-disubstituted tetrazoles on treatment of imidoyl-
benzotriazoles with NaN3, where the protocol required 1 eq. TFA and 0.2 eq.
TBAB in a (1:1) mixture of H2O/CH2Cl2.[14b] Interestingly, imidoyl azides, ob-
tained by the reaction of cyanogen azide with primary amines on intramolec-
ular cyclization, also affords 1-substituted aminotetrazoles.[14c] Haira et al.
reported Zn(OTf)2-catalyzed one-pot reaction of nitriles, alkenes, NBS, and
TMSN3 to provide 1,5-disubstituted tetrazoles containing an additional α-
bromo functionality of the N1-alkyl substituent.[15a] Treatment of isocyanide
dibromides with NaN3 followed by electrocyclization and a Suzuki coupling af-
fords a good yield of tetrazoles.[15b] Synthesis of fused tetrazoles is also well
documented in the literature. Representative examples include the synthesis
of tetrazolo[1,5-a]pyridines starting from pyridine N-oxides on reaction with
diphenyl phosphorazidate and pyridine (2 eq.) under solvent-free condition.[16]
TBAF-catalyzed reaction of 2-halopyridines with TMSN3 also gave similar
fused heterocycles.[17]
Despite the huge potential of carbohydrate-containing tetrazole skeletons
to offer promising chemotherapeutic potential, their syntheses through simple
protocols is still challenging. The known methods have limitations, including
requirement of an acidic catalyst that may cause removal of the isopropylidene
protection of carbohydrate, involvement of two or more steps, average reaction
yield, and, moreover, the limited availability of starting material. Based on a
literature search, there is not a single report available to deal with the synthe-
sis of carbohydrate-containing tetrazole using benzotriazole chemistry. Herein,
we present a simple and facile protocol for the synthesis of a novel glycosyl
tetrazole using benzotriazole methodology.
RESULTS AND DISCUSSION
Synthesis of glycosylated tetrazole surfaced due to our consistent interest in a
long-standing research program on devising new synthetic strategies for phar-
macologically important carbohydrate and heterocyclic scaffolds by employing
benzotriazole methodology.[18] During the course of these studies we set out to
explore the feasibility of utilizing recently developed glycosyl carboxamides[19]
with sugar in furanose and pyranose form as precursors to access a broad range
of diverse carbohydrate-containing tetrazoles. A close look at the structure of
carboxamide inspired us to envisage two different strategies to furnish the

Synthesis of Novel Glycosyl Tetrazole
133
glycosylated tetrazole via an imidoylbenzotriazole intermediate. The strategy
first encompasses the treatment of BtTMS complex with SOCl2 at 0◦C to af-
ford the sulfenyl dibenzotriazole, which on further treatment with carboxam-
ide yields imidoylbenzotriazole. This route was found to be very cumbersome
and led to poor yield of the desired product. Then eventually we employed a
second strategy to synthesize imidoylbenzotriazole, where carboxamide (1) was
treated with oxalyl chloride, pyridine, and benzotriazole in anhydrous CH2Cl2
and the formed imidoylbenzotriazole (2) was directly used in next step as de-
picted in Scheme 1. In the above dried mass, anhydrous DMF and sodium
azide were added and the reaction was continued for 10 to 11 h. The product
1
was isolated by column chromatography (SiO2) and characterized by H and
13C NMR, IR, and elemental analysis.
OBn
O
O
H
R
N
N
BtH, Py, (COCl)2, DCM, 0-40 °C,
7-8 h, NaN3, DMF, 50 oC, 10-11 h
R
N
H
OBn
O
N
N
O
H
O
R
O
OBn
O
N
O
1a-h
3a-h
N
N
O
N
O
Ref. 19
D(+) Glucose
Intermediate
2a-h
Scheme 1: Benzotriazole-mediated synthesis of glycosyl 1H-tetrazole C-nucleosides.
Next, we studied the individual effect of catalysts such as TFA (one to two
drops) and TBAB, where no significant effect was noticed on the yield of the
reaction. The 1,2-isopropylidene protection in the glycosyl imidoylbenzotrizole
was found to be stable during the course of the reaction even in the presence
of one to two drops of TFA. In order to find a suitable solvent, we investi-
gated the effect of various solvents upon yield as well as reaction duration and
observed that CH2Cl2, benzene, and CHCl3 took more time to afford the de-
sired glycosyl tetrazole, whereas DMF furnished the desired compound in good
yield and proved to be the most suited solvent for this synthesis. Cyclization of
imidoylbenzotrizole leading to the tetrazole ring is mechanistically driven by
aromatization force. With optimum condition in hand, we treated cyclopropyl,
cyclohexyl, n-hexadecyl, n-octyl, phenylethyl, 4-phenylthiazole, thiadiazole,
and oxadiazole-containing glycosyl imidoylbenzotriazoles with NaN3 in DMF
to afford the desired glycosyl tetrazoles (3a–h) in good yields (Table 1).
The proposed reaction mechanism is presented in Scheme 2. At the out-
set of the reaction, the delocalization of a lone pair of electrons of nitrogen
of carboxamide 1 initiates the attack on carbonyl carbon of oxalyl chloride to

R.R. Kale et al.
134
O
Cl
Cl
O
Cl
R
O
O
OBn
O
N
OBn
O
OBn
O
O
O
R
R
N
N
N
N
O
O
O
H
N
N
Cl
O
H
O
O
N
1
2
I
N
Na
N=N=N
R
R
N
N
N
OBn
O
N
N
OBn
N
Cyclization
O
N
O
N
O
O
O
3
II
Scheme 2: Proposed reaction mechanism for the formation of glycosyl tetrazole 3.
Table 1: Synthesis of glycosyl tetrazole (3a–h)
Glycosyl
amide (1a–h)
Reaction
condition
Yield
(%)a
Entry
1
Product (3a–h)
Toluene, 15 h
55
2
3
4
5
6
1a
1a
1a
1a
1a
3a
3a
3a
3a
3a
C6H6, 15 h
40
45
46
80
80
CH2Cl2, 15 h
CHCl3, 15 h
DMF, 11 h
DMF, TFA, 11 h
7
DMF, 11 h
78
(Continued on next page)

Synthesis of Novel Glycosyl Tetrazole
135
Table 1: Synthesis of glycosyl tetrazole (3a–h) (Continued)
Glycosyl
amide (1a–h)
Reaction
condition
Yield
(%)a
Entry
8
Product (3a–h)
DMF, 10 h
73
9
DMF, 10 h
76
10
DMF, 10 h
DMF, 10 h
77
74
11
12
13
DMF,10 h
DMF, 10 h
70
71
aYields refer to the isolated pure product.

R.R. Kale et al.
136
give the ester intermediate I, which on substitution reaction by benzotriazole
fetches the imidoylbenzotriazole intermediate 2. Then benzotriazole is cleaved
by addition of sodium azide to provide the intermediate II, which on subse-
quent cyclization leads to formation of desired glycosyl triazole 3. The struc-
1
tures of the synthesized compounds were confirmed on the basis of IR and H
and 13C NMR spectroscopic data. In the 13C NMR spectra, quaternary carbon
of tetrazole appeared in between δ 155 and 157 with other furanose peaks and
thus clearly substantiated the formation of the desired glycosyl tetrazoles.
CONCLUSION
In conclusion, a facile protocol for diverse novel carbohydrate-containing tetra-
zole has been developed using benzotriazole methodology. The method is ad-
vantageous as it is one pot, involves mild reaction conditions, and affords the
products in good to excellent yields. The developed glycosyl tetrazoles bearing
different heterocyclic skeletons at 1-position may show promising bioactivities
and can serve as a pharmacologically important carbohydrate-based scaffold.
EXPERIMENTAL SECTION
All the solvents and reagents were purchased from Sigma-Aldrich and puri-
fied by standard techniques. Thin layer chromatography (TLC) was performed
using silica gel 60 F-254 plates with I2 vapors as the detecting agent followed
by H2SO4 spray. Crude products were purified by column chromatography on
silica gel 230–400 mesh. Solvents were evaporated under reduced pressure
at temperature <55◦C. TMS (0.0 ppm) was used as an internal standard in
1H NMR and in 13C NMR. Infrared spectra were recorded as KBr pellets by
a Perkin Elmer RX-1 spectrometer. Elemental analyses were performed on a
Perkin-Elmer 2400 C, H, N analyzer and values were found to be within 0.5%
of the calculated values.
Typical Experimental Procedure for Synthesis of Glycosyl
Tetrazole (3a–h)
To a solution of N-cyclopropyl-3-O-benzyl-1,2-O-isopropylidene-α-D-xylo-
furanuron amide (1a, 0.5 g, 1.50 mmol) in dry CH2Cl2 (25 mL), pyridine (0.13
mL, 1.50 mmol) and oxalyl chloride (0.13 mL, 1.50 mmol) were added slowly at
0◦C under constant stirring. After 15 min, benzotriazole (0.375 g, 3.153 mmol)
was added and reaction was further stirred for 15 min and then allowed to be
continued for 7 h at 40◦C. Progress of reaction was monitored with TLC (20%
EtOAc in n-hexane) and after completion, the reaction mixture was treated
with 10% Na2CO3 aq. solution, extracted with CH2Cl2, and evaporated under

Synthesis of Novel Glycosyl Tetrazole
137
vacuum. Crude mass thus obtained was dissolved in dry DMF (20 mL) followed
by the addition of NaN3 (0.572 g, 8.94 mmol) at 50◦C and kept under constant
stirring. Progress of the reaction was monitored with TLC (40% EtOAc in n-
hexane) and found to be completed after 10 h. Then the reaction mixture was
concentrated under vacuum, extracted with CH2Cl2 (2 × 20 mL), and dried
over anhydrous Na2SO4. The solvent was evaporated, and the crude product
was subjected to flash column chromatography (SiO2) to give desired glycosyl
tetrazole (3a) in good yield.
N1-Cyclopropyl-5-(3ꢁ-O-benzyl-1,2-O-isopropylidene-α-D-xylo-furano-4ꢁ-yl)-
tetrazole (3a)
Yield: 80%; IR (KBr): νmax cm−1 1673.6, 2921.1; 1H NMR (CDCl3, 300 MHz):
δ = 0.53 and 0.79 (each m, each 2 H, cyclopropyl-CH2), 1.31 and 1.47 [each s,
each 3 H, 2 × >C(CH3)2], 2.78 (m, 1 H, cyclopropyl-CH), 4.37 (d, J = 3.0 Hz,
1 H, H-3), 4.58 (m, two d merged, OCHAPh, 2 H, H-2 and OCHBPh), 4.76 (d,
J = 3.3 Hz, 1 H, H-4), 5.97 (d, J = 3.3 Hz, 1 H, H-1), 7.26–7.44 (m, 5 H, Ar-H);
13C NMR (CDCl3, 75 MHz): δ = 6.34, 6.40, 22.11, 26.31, 26.91, 73.14, 81.04,
82.41, 82.45, 105.47, 112.77, 114.96, 127.67, 127.96, 128.27, 128.39, 137.04,
138.89, and 156.0 ppm. Anal. Calcd for C18H22N4O4: C 60.32, H 6.19, N 15.63;
found C 60.61, H 6.05, N 15.84.
N1-Cyclohexyl-5-(3ꢁ-O-benzyl-1,2-O-isopropylidene-α-D-xylofurano-4ꢁ-yl)-
tetrazole (3b)
Reaction of N-cyclohexyl-3-O-benzyl-1,2-O-isopropylidene-α-D-xylofuranu
ronamide (2b) with oxalyl chloride, BtH followed by treatment with NaN3, and
workup as described above, and flash column chromatography gave glycosyl
tetrazole 3b as colorless foam. Yield: 78%; IR (KBr): νmax cm−1 1677.5, 2943.3;
1H NMR (CDCl3, 300 MHz): δ = 1.16–1.87 [m, 16 H, cyclohexyl-CH2 and 2 ×
>C(CH3)2 merged], 3.82 (m, 1 H, cyclohexyl-CH), 4.35 (d, J = 3.0 Hz, 1 H, H-3),
4.58 (d, J = 8.1 Hz, 1 H, OCHAPh), 4.59–4.65 (m, 2 H, OCHBPh and H-2), 4.72
(d, J = 2.7 Hz, 1 H, H-4), 5.98 (d, J = 3.3 Hz, 1 H, H-1); 13C NMR (CDCl3, 75
MHz): δ = 24.63, 24.66, 25.35, 26.30, 26.89, 32.68, 32.88, 47.98, 73.06, 80.97,
82.39, 82.45, 105.40, 112.68, 125.61, 127.66, 127.85, 128.27, 137.13, and 154.96
ppm. Anal. Calcd for C21H28N4O4: C 62.98, H 7.05, N 13.99; found C 63.17, H
7.11, N 14.06.
N1-n-Hexadecyl-5-(3ꢁ-O-benzyl-1,2-O-isopropylidene-α-D-xylofurano-4ꢁ-yl)-
tetrazole (3c)
Reaction of N-hexadecyl-3-O-benzyl-1,2-O-isopropylidene-α-D-xylofuranu
ronamide (2c) with oxalyl chloride, BtH followed by treatment with NaN3 and
workup as described above, and flash column chromatography gave glycosyl
tetrazole 3c as colorless foam. Yield 73%; IR (KBr): νmax cm−1 1671.3, 2918.4;

R.R. Kale et al.
138
1H NMR (CDCl3, 300 MHz): δ = 0.88 (t, J = 6.6 Hz, 3 H, CH3), 1.25 (m, 28 H,
CH2), 1.31 and 1.48 (each s, each 3 H, 2 × >C(CH3)2), 3.29 (m, 2 H, CH2), 4.35
(d, J = 2.7 Hz, 1 H, H-3), 4.59–4.61 (m, 3 H, H-2, OCHAPh and OCHBPh), 4.73
(d, J = 2.7 Hz, 1 H, H-4), 5.98 (d, J = 3.3 Hz, 1 H, H-1), 7.29 (m, 5 H, Ar-H);
13C NMR (CDCl3, 75 MHz): δ = 14.11, 22.65, 26.34, 26.84, 26.92, 29.25, 29.33,
29.49, 29.57, 29.66, 31.89, 39.10, 73.17, 81.09, 82.38, 82.59, 105.40, 112.62,
127.68, 127.88, 128.36, 137.24, and 156.3 ppm. Anal. Calcd for C31H50N4O4: C
68.60, H 9.29, N 10.32; found C 68.73, H 9.36, N 10.42.
N1-n-Octyl-5-(3ꢁ-O-benzyl-1,2-O-isopropylidene-α-D-xylofurano-4ꢁ-yl)-
tetrazole (3d)
Reaction of N-octyl-3-O-benzyl-1,2-O-isopropylidene-α-D-xylo- furanuron-
amide (2d) with oxalyl chloride, BtH followed by treatment with NaN3 and
workup as described above, and flash column chromatography gave glycosyl
tetrazole 3d as colorless foam. Yield 76%; IR (KBr): νmax cm−1 1679.3, 2912.1;
1H NMR (CDCl3, 300 MHz): δ = 0.87 (d, J = 6.6 Hz, 3 H, CH3), 1.25 (m, 12 H,
CH2), 1.31 and 1.47 (each s, each 3 H, 2 × >C(CH3)2), 3.31 (t, J = 6.6 Hz, 2
H, NCH2), 4.35 (d, J = 3.0 Hz, 1 H, H-3), 4.57 (d, J = 3.6 Hz, 1 H, H-2), 4.59
(d, J = 11.7 Hz, 1 H, OCHAPh), 4.65 (d, J = 11.7 Hz, 1 H, OCHBPh), 4.74 (d,
J = 3.0 Hz, 1 H, H-4), 5.99 (d, J = 3.6 Hz, 1 H, H-1), 7.25–7.31 (m, 5 H, Ar-H);
13C NMR (CDCl3, 75 MHz): δ = 14.05, 22.59, 26.35, 26.82, 26.93, 29.12, 29.19,
29.49, 31.76, 39.03, 73.18, 81.11, 82.41, 82.61, 105.44, 112.63, 127.69, 127.90,
128.37, 137.28, 138.0 and 155.89 ppm. Anal. Calcd for C23H34N4O4: C 64.16, H
7.96, N 13.01; found C 64.22, H 8.01, N 13.12.
N1-Phenylethyl-5-(3ꢁ-O-benzyl-1,2-O-isopropylidene-α-D-xylofurano-4ꢁ-yl)-
tetrazole (3e)
Reaction of N-phenylethyl-3-O-benzyl-1,2-O-isopropylidene-α-D-xylofura
nuronamide (2e) with oxalyl chloride, BtH followed by treatment with NaN3
and workup as described above, and flash column chromatography gave gly-
cosyl tetrazole 3e as colorless foam. Yield 77%; IR (KBr): νmax cm−1 1672.9,
1
2932.5; H NMR (CDCl3, 300 MHz): δ = 1.31 and 1.47 [each s, each 3H, 2 ×
>C(CH3)], 2.79 (t, J = 6.6, 2 H, CH2), 3.58 (m, 2 H), 4.37 (d, J = 3.3 Hz, 1 H,
H-3), 4.57 (d, J = 10.8 Hz, 1 H, OCHAPh), 4.58 (d, J = 10.8 Hz, 1 H, OCHBPh),
4.60 (d, J = 3.6 Hz, 1 H, H-2), 4.77 (d, J = 3.0 Hz, 1 H, H-4), 5.96 (d, J =
3.6 Hz, 1 H, H-1), 7.26–7.48 (m, 10 H, Ar-H); 13C NMR (CDCl3, 75 MHz): δ =
26.28, 26.91, 35.66, 40.39, 73.08, 81.10, 82.32, 82.49, 105.50, 112.81, 125.98,
126.50, 127.71, 127.99, 128.39, 128.55, 128.63, 137.00, 138.77, 138.84, 138.90,
and 156.23 ppm. Anal. Calcd for C23H26N4O4: C 65.39, H 6.20, N 13.26; found
C 65.47, H 6.32, N 13.35.

Synthesis of Novel Glycosyl Tetrazole
139
N1-2-(4-Phenyl-thiazol-2-yl)-5-(3ꢁ-O-benzyl-1,2-O-isopropylidene-α-D-
xylofurano-4ꢁ-yl)-tetrazole (3f)
Reaction of N-2-(4-Phenyl-thiazol-2-yl)-3-O-benzyl-1,2-O-isopropylidene-
α-D-xylofuranuronamide (2f) with oxalyl chloride, BtH followed by treatment
with NaN3 and workup as described above, and flash column chromatography
gave glycosyl tetrazole 3f as colorless foam. Yield: 74%; IR (KBr): νmax cm−1
1676.6, 2945.1; 1H NMR (CDCl3, 300 MHz): δ = 1.35 and 1.60 [each s, each 3H,
2 × >C(CH3)2], 4.43 (d, J = 3.0 Hz, 1 H, H-3), 4.57–4.64 (m, 3 H, OCHAPh,
OCHBPh, H-4), 4.97 (d, J = 3.3 Hz, 1 H, H-2), 6.15 (d, J = 3.0 Hz, 1 H, H-
1
1), 7.17–7.84 (m, 11 H, Ar-H); 13C NMR (CDCl3, 75 MHz): H NMR (CDCl3,
75 MHz): δ = 26.32, 27.02, 73.01, 80.95, 82.34, 82.55, 105.96, 107.81, 113.04,
125.68, 126.03, 127.55, 127.92, 128.03, 128.32, 128.70, 134.23, 136.64, 150.07,
and 156.56 ppm. Anal. Calcd for C24H23N5O4S: C 60.36, H 4.85, N 14.67; found
C 60.45, H 4.80, N 14.74.
N1-(5-Phenyl-[1,3,4]thiadiazol-2-yl)-5-(3ꢁ-O-benz-yl-1,2-O-isopropylidene-α-D-
xylofurano-4ꢁ-yl)-tetrazole (3g)
Reaction
of
N-(5-Phenyl-[1,3,4]
thiadiazol-2-yl)-3-O-benzyl-1,2-O-
isopropylidene-α-D-xylofuranuronamide (2g) with oxalyl chloride, BtH
followed by treatment with NaN3 and workup as described above, and flash
column chromatography gave glycosyl tetrazole 3g as colorless foam. Yield
70%; IR (KBr): νmax cm−1 1673.9, 2934.2; 1H NMR (CDCl3, 300 MHz): δ = 1.31
and 1.51 [each s, each 3 H, 2 × >C(CH3)2], 4.46 (d, J = 3.3 Hz, 1 H, H-3), 4.54
(d, J = 11.7 Hz, 1 H, OCHAPh), 4.58 (d, J = 12.0 Hz, 1 H, OCHBPh), 4.64 (d,
J = 3.3 Hz, 1 H, H-2), 5.02 (d, J = 3.3 Hz, 1 H, H-4), 6.18 (d, J = 3.3 Hz, 1 H,
H-1), 7.16–7.96 (m, 10 H, Ar-H); 13C NMR (CDCl3, 75 MHz): δ = 26.28, 26.99,
72.66, 80.97, 82.17, 82.49, 106.03, 112.90, 127.19, 127.48, 127.87, 128.25,
128.99, 130.26, 130.53, 136.48, and 156.62 ppm. Anal. Calcd for C23H22N6O4S:
C 57.73, H 4.63, N 17.56; found C 57.86, H 4.69, N 17.64.
N1-(5-Phenyl-[1,3,4]thiadiazol-2-yl)-5-(3ꢁ-O-benzyl-1,2-O-isopropylidene-α-D-
xylofurano-4ꢁ-yl)-tetrazole (3h)
Reaction
of
N-(5-Phenyl-[1,3,4]
thiadiazol-2-yl)-3-O-benzyl-1,2-O-
isopropylidene-α-D-xylofuranuronamide (2h) with oxalyl chloride, BtH
followed by treatment with NaN3 and workup as described above, and flash
column chromatography gave glycosyl tetrazole 3h as colorless foam. Yield
71%; IR (KBr): νmax cm−1 1671.7, 2929.1; 1H NMR (CDCl3, 300 MHz): δ = 1.33
and 1.50 [each s, each 3 H, 2 × >C(CH3)2], 4.43 (d, J = 3.3 Hz, 1 H, H-3),
4.51–4.70 (m, 3 H, OCHAPh, H-2 and OCHBPh), 4.99 (d, J = 3.3 Hz, 1 H, H-4),
6.14 (d, J = 3.3 Hz, 1 H, H-1), 7.16–7.95 (m, 10 H, Ar-H); 13C NMR (CDCl3,
75 MHz): δ = 26.35, 27.10, 73.16, 81.0, 82.32, 82.62, 106.09, 113.34, 127.12,
127.38, 127.59, 128.13, 128.40, 128.50,128.96, 129.17, 130.33, 130.75, 136.55,

R.R. Kale et al.
140
and 155.26 ppm. Anal. Calcd for C23H22N6O5: C 59.73, H 4.79, N 18.17; found
C 59.79, H 4.81, N 18.22.
ACKNOWLEDGEMENTS
The authors thank CISC, BHU for providing spectroscopic and analytical data
of synthesized compounds. Council of Scientific & Industrial Research and Uni-
versity Grant Commision, New Delhi, India, is gratefully acknowledged for
funding.
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