Metal-Free Route to Carboxylated 1,4-Disubstituted 1,2,3-Triazoles from Methoxycarbonyl-Modified Vinyl Sulfone

Article abstract of DOI:10.1021/acs.joc.9b02443

A metal-free alternative to the regioselective synthesis of carboxylated 1,4-disubstituted 1,2,3-triazoles (1,4-cDTs) has been accomplished. A methoxycarbonyl-substituted vinyl sulfone on reactions with organic azides resulted in the formation of 1,4-cDTs

Full text of DOI:10.1021/acs.joc.9b02443

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Article
A Metal-free Route to Carboxylated 1,4-Disubstituted 1,2,3-
Triazoles from Methoxycarbonyl Modified Vinyl Sulfone
Jayanta Das, Santu Dey, and Tanmaya Pathak
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b02443 • Publication Date (Web): 28 Oct 2019
Downloaded from pubs.acs.org on October 28, 2019
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A Metal-free Route to Carboxylated 1,4-Disubstituted 1,2,3-Triazoles from
Methoxycarbonyl Modified Vinyl Sulfone
Jayanta Das, Santu Dey and Tanmaya Pathak*
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Department of Chemistry, Indian Institute of Technology Kharagpur
Kharagpur 721 302, West Bengal, India
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Dedicated to Professor Jyoti Chattopadhyaya on occasion of his 70th birthday
KEY WORDS: vinyl sulfone; carboxylated 1,4-disubstituted 1,2,3-triazoles; carboxylated
triazoles; bis-triazoles; 1,3-dipolar cycloaddition
ABSTRACT
A metal-free alternative to the regioselective synthesis of carboxylated 1,4-disubstituted
1,2,3-triazoles (1,4-cDTs) has been accomplished. A methoxycarbonyl-substituted vinyl
sulfone on reactions with organic azides resulted in the formation of 1,4-cDTs in an
operationally simple route. The reaction, carried out with a variety of organic azides
containing free alcohol, acid, Boc-protected amine, ester, protected sugars, long chain
alkanes, benzyl, 9-methylanthracenyl and cholesteryl groups were found to be general in
nature, which afforded a plethora of new chemical entities; reactions of diazides generated
mostly the desired and a few unexpected products. This manuscript reports for the first time
the targeted metal-free synthesis of any 1,4-disubstituted 1,2,3-triazole using the
cycloaddition reactions of an appropriately functionalized vinyl sulfone.
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INTRODUCTION
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The in-built general structural features of 1,2,3-triazoles have high aromatic stability, H-bond
forming ability, dipole–dipole and −stacking interactions and considerble metabolic
stability. All these properties are highly desirable in biomedical research as well as in material
sciences.1 Although 1,2,3-triazole preparation from phenyl azide and dimethyl
acetylenedicarboxylate was reported way back in 1893,2a the real potential of the reaction
was revealed during 1960s and the reaction came to be known as the ‘Huisgen
cycloaddition’ reaction.2b In particular, ‘Huisgen cycloaddition’ demonstrates one-pot
formation of the two regioisomers 1,4- and 1,5-disubstituted 1,2,3-triazoles at approximately
equal proportions from the thermal reaction of terminal alkynes with organic azides. The
versatility of the cycloaddition approach of azides to terminal alkynes was realized soon with
Huisgen’s fundamental finding.2b However, the Cu(I)-catalyzed Azide-Alkyne Cycloaddition
(CuAAC) discovered by Meldal and Sharpless independently3 triggered interests on the
synthesis and evaluation of one of the two regioisomers, the 1,4-disubstituted-1,2,3-triazoles
(1,4-DTs). The last one-and-half decades have witnessed substantial impact of a large number
of 1,4-DTs in research and applications in almost all advanced areas of chemistry. This
particular class of triazoles have been widely used in polymer, medicinal and chemical
biology research.4
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Notably, 4-carboxylated-1,4-DTs (1,4-cDTs) have recently attracted interest due to their
potential biological activities. Rufinamide, an anticonvulsant drug 1a can be easily prepared
from the methyl carboxylate precursor 1b (Figure 1).5a Promising cytotoxicity was associated
with methylcarboxylate-substituted 1,4-cDT-containing podophyllotoxin 2.5b -Glucosidase
and dipeptityl peptidase-4 inhibitory activities (useful for diabetes mellitus type 2) were
associated with the methylcarboxylate 1,4-cDTs 3.5c 1,4-cDTs 4a and 4b were found suitable
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as leishmanicidal and antichagasic chemotherapeutic agents respectively.5d 1,4-cDT
derivative 5 was studied as a new α-glucosidase inhibitor.5e A limited number of bis- or poly
1,4-cDTs have also been synthesized and studied.6 A series of geminal carboxylated
tristriazole compounds have been prepared and the six ester groups in the periphery of the
nitrogen rich system 6a provided the starting material for dendritic structures.6a Antioxidant
activities of a series of β-elemene dimer derivatives like 6b and 6c were studied in hydrogen
peroxide-injured human umbilical vein endothelial cells.6b It should be noted that all these
carboxylated triazoles barring one set 1b were synthesized using CuAAC strategy (Figure
1).5,6 Requisite metal catalyst has imposed limitation of the CuAAC concept in areas such as
chemical biology and photophysical chemistry. As a consequence, metal-free alternative
routes to the regioselective formation of 1,4-DTs was looked into although general methods
are limited in the literature.7 However, as far as our knowledge goes into literature there are
only a few reports on the metal free synthesis of 1,4-cDTs.5a,8
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Taking a cue from the report that vinyl sulfoxides are acetylene equivalents,9 we have
demonstrated that vinyl sulfones, a novel group of Michael acceptors can also efficiently
participate in [3+2] cycloaddition reactions as 2 partners with organic azides to afford 1,5-
DTs.10a,b,d In comparison to many other electron deficient olefins, vinyl sulfones, are easily
prepared from diols, dibromides, epoxides aldehydes, olefins etc11a and can be easily
incorporated even into complex organic molecules like carbohydrates.11b With the help of
DFT calculations along with experimental findings, we have shown previously that the
regioselectivity of triazole formation for the cycloaddition of azides and vinyl sulfones, is
controlled by the substituents attached to the olefinic unit.10c Thus, the [3+2]-cycloaddition
reactions of the methylcarboxylate-substituted vinyl sulfone 7 with organic azides was
predicted to selectively afford 1,4-cDT because the DFT (M06-L/6-311+G(d,p)//M06-L/6-
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Figure 1. Selected examples of reported 4-carboxylated-1,4-DTs (1,4-cDTs)
31+G(d) calculated results in toluene established10c that the transition state leading to the
formation of the 1,4-cDT was favored over its 1,5-cDT isomer by 5.8 kJ/mol; moreover, the
calculated free energy of activation ΔG⧧ at M06-L/6-31+G(d) level also predicted similar
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regioisomeric preference. Interestingly, the distortion and interaction energies for the
cycloadditions of 7 in toluene, calculated at the M06-L/6-311+G(d,p)//M06-L/6-31+G(d)
level of theory revealed that the regioselectivity generally arose due to the differences in the
distortion energies of reactants rather than their frontier molecular orbital (FMO)
interactions.10c Therefore, the [3+2]-cycloaddition reactions of the methylcarboxylate-
substituted vinyl sulfone 7 with organic azides is expected to proceed through an
intermediate A, followed by the elimination of p-TolSO2H (Scheme 1). In the process, in a
departure from the usual formation of 1,5-DTs from vinyl sulfones reported so far,10a,b,d the
carboxylated vinyl-sulfone would generate a series of 1,4-cDTs.
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Scheme 1. Plausible mechanism for the formation of 1,4-cDTs from vinyl sulfone 7
RESULTS AND DISCUSSION
The carboxylic acid-substituted vinyl sulfone 9 was prepared from 2,3-dibromopropionic acid
8 by slight modification of the earlier report.2 The treatment of the acid 9 with methyl iodide
in the presence of 1,8-diazabicyclo-[5,4,0]-undec-7-ene (DBU) at room temperature afforded
the methyl ester 7 (Scheme 2). Initially, to test the cycloaddition reactions ‘on-water’10a
methylcarboxylate-substituted vinyl sulfone 7 was reacted with the sugar azide 10, in
refluxing water which afforded the 4-carboxylated 1,4-disubstituted 1,2,3-triazole 11 in
moderate yield (52%, Scheme 3) whereas benzylazide, under identical reaction conditions
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Scheme 2. Preparation of carboxylate-substituted vinyl sulfone 7
Scheme 3. Reactions of vinyl sulfone 7 with organic azides in water or water/t-butanol
mixture.
furnished the desired triazole 12 in only 36% isolated yield (Scheme 3). 1,4-cDT 12 was
obtained in 57% yield and 11 was formed as a mixture (1H-NMR) when the reactions were
performed in t-butanol-water (1:1) system. It should be noted that to protect the acid labile
isoprolylidene group from sulfinic acid, generated in the reaction (Scheme 1), it was
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necessary to use one equivalent of NaHCO3 in the reaction media.10a In the presence of
NaHCO3, however in pure water as well as in t-butanol-water system, the triazole 11
underwent partial decarboxylation. It was clear from the 1H-NMR of the reaction mixture of
10 that one of the major products resulted from the decarboxylation (in the presence of
NaHCO3) or deprotection (in the absence of NaHCO3). Acid hydrolysis of the ester group by
sulfinic acid was also a possibility.
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Isolation of these two products in poor to moderate yields led us to screen different solvents.
To optimize the effect of the solvent on the reaction, benzyl azide was chosen as the model
azide. The reaction was faster in DMF but it resulted in comparatively lower yield of the
product (Table 1, entry 3). The reaction was also attempted in toluene, ionic liquid N,N-
dimethylethanolammoniumformate,10k and in ionic liquid-water (1:1) mixture. In these
solvents, though the reactions required shorter time, the product 12 was obtained in
unsatisfactory yield (Table 1, entries 4-6). Among the solvents tested for the reaction of vinyl
Table 1. Screening of some selective solvents for the reaction of vinyl sulfone 7 with benzyl
azide.a
Entry Solvent
Reaction
conditions
Yield
(%)b
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t-BuOH-water
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reflux, 24h
reflux, 20h
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100oC, 18h
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toluene
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water:ILc
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DMSO
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aAll the reactions were performed on 100 mg (0.4 mmol) of vinyl sulfone and 54 mg (0.4 mmol) of
benzyl azide in 1 mL of solvent.
bIsolated pure compounds from flash column chromatography.
cIonic liquid:N,N-dimethylethanolammoniumformate was used.
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sulfone 7 with benzyl azide, DMSO was found to be the most suitable in terms of product
yields (Table1, entry 7).
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The scope of various organic azides was then investigated with the optimized reaction
conditions. The results are summarized in scheme 4. The reaction was found viable with
organic azides having wide ranging functional groups. Thus, the optimized reaction condition
allowed the [3+2] dipolar cycloaddition of methylcarboxylated vinyl sulfone 7 with organic
azides containing free alcohol, carboxylic acid, protected amine, ester, protected sugars, long
chain alkanes, benzyl, 9-methylanthracenyl and cholesteryl units to result in the
corresponding 1,4-cDTs 11-24 in moderate to very good yields (Scheme 4; for structural
elucidation see later). Compound 12 was prepared in relatively larger scale using 5 mmol of
7. The formation of 1,4-cDTs can be explained on the basis of the plausible mechanism
proposed in scheme 1 and the theoretical justification discussed above.10c
The reported importance of bis- and polytriazoles 6a-c (Figure 1) prompted us to study the
efficiency of vinyl sulfone 7 as the 2 partner for reactions with different diazides. Thus,
carboxylated vinyl sulfone 7 on reactions with the diazide 25 afforded partially triazolylated
but expected monotriazole 26 in 17% yield after 6 h. Surprisingly, the unsymmetrical
bistriazole 27 containing both 1,4-cDT and 1,5-cDT residues was obtained as the major
compound in 33% yield. Additionally a symmetrical 1,5-cDT containing bistriazole 28 was
also isolated in minor amount although the presence of the monotriazolylated 1,5-cDT
regioisomer of 26 could not be spotted (Scheme 5; for structural elucidation see later).
Reactions of 7 with another set of diazides 29a and 29b afforded more complex mixtures in
each case (Scheme 6). Thus, 1,1'-oxybis[2-azidoethane] 29a on reactions with 7 afforded
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a2eqv. NaHCO3 was added; b2 eqv. azide was used.
Scheme 4. Synthesis of 4-carboxylated 1,4-DTs
once again the partially triazolylated but expected monotriazole 30a in 18% yield as well as
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the unexpected monotriazole 31a as a minor product. The expected symmetrical 1,4-cDT
bistriazole 32a was the major product along with the unsymmetrical bistriazole 33a
containing both 1,4-cDT and 1,5-cDT residues which was formed as a minor compound. No
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Scheme 5. Reaction of 7 with diazide 25
Scheme 6. Reactions of 7 with diazides 29a and 29b
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symmetrical 1,5-cDT containing bistriazole 34a was obtained in this case (Scheme 6; for
structural elucidation see later). In continuation with this study, N,N-bis(2-azidoethyl)-4-
methyl- benzenesulfonamide 29b on reactions with 7 afforded a separable mixture of
monotriazoles 1,4-cDT 30b (21%), 1,5-cDT 31b (9%) along with bistriazoles 1,4-cDT/1,4-
cDT 32b (38%), 1,4-cDT/1,5-cDT 33b (8%) and 1,5-cDT/1,5-cDT 34b (6%). All these
products were separated by column chromatography and their regioisomeric nature was
established (Scheme 6; for structural elucidation see later). Several attempts to obtain minor
compounds 28, 31a and 33b in pure form failed; however, these compounds were included to
highlight the unusual complexity of the cycloaddition reactions of 7 and diazides.
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In all reactions of diazides 25 and 29a-b, the reactions were allowed to continue till the
disappearance of 7 (tlc) to avoid side-product formation. This explains the poor yields of
bistriazoles although the formation of 1,5-cDTs or bistriazoles containing both 1-4-cDT and
1,5-cDT units were surprising. Whether the monotriazoles 26, 30a-b or 31a-b got involved
into reorganization of the long tail to control the outcome of the reactions remain to be
established. On the other hand the known12 interactions of the carbonyl group present in 7 or
monotriazoles formed in the reaction media may contribute to the nature of products isolated
from the reaction media.
The structural assignment of 1,2,3-triazoles carrying neutral groups is normally done by using
the well-established general principle that Δ (δC4−δC5)-1,4-DTs>>Δ (δC4−δC5)-1,5-DTs.13a
Later, the proton decoupled 13C chemical shifts of C4 (1,5-DT) or C5 (for 1,4-DT) were
utilized for identifying the regioisomers.13b However, it was reported that an ester group (or
carbonyls) attached to C4 or C5 of 1,2,3-triazoles moved both C4 (1,5-DT) or C5 (1,4-DT)
chemical shifts towards a higher value (downfield) by approximately 6 ppm.13b Under the
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circumstances, Δ (δC4−δC5) values for both the isomers get closer as depicted in figure 2 for
a pair of triazoles 35a/35b14 and become an unreliable tool for the structural assignments. It
is evident that the Δ (δC4−δC5) values of compounds 11 and 18, were found to be 12.1 and
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Figure 2. 13C-NMR data of known pairs 35a and 35b14
11.0 respectively; the corresponding values for rest of the compounds in this series were
found to be ≥10 ppm. In the absence of the other isomer, the NMR assignment would have
led to erroneous conclusion for this class of compounds. Therefore triazoles 19 and 20 were
synthesized from propiolic acid 36 using CuAAC (Scheme 7) via carboxylates 37/38 and
were found to be identical with the 1,4-cDTs obtained from vinyl sulfone 7 (Scheme 4). The
Δ(δC4−δC5) values of 1,2,3-triazoles obtained from the diazides (schemes 5 and 6) were also
found to be ≥10.12
For bistriazoles, one singlet at 8.11 ppm of compound 28 (Table S1) along with the absence
of azido group as well as its HRMS value indicated the presence of two similar types of
1,2,3-triazole rings in this bistriazole compound. On the other hand, the presence of two
singlets at 8.08 ppm and 8.13 ppm in the 1H-NMR spectrum of compound 27 indicated the
presence of two different regioisomeric triazoles. For unsymmetrical 27 two Δ(δC4−δC5)
values (12.3/10.5 ppm) and for the symmetrical 28 one value (9.5 ppm) were generated.
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Although it was obvious that 27 was functionalized with both 1,4-cDT and 1,5-cDT, the
identity of triazole residue in 28 was established in an indirect way. Thus, compounds 26 and
41 were synthesized from the propiolic acid 36 via acids 39 and 40 respectively (Scheme 8).
1,4-cDT 26 was identical (Table S1; see SI) to the product obtained from vinyl sulfone 7
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Scheme 7. Alternative synthesis of triazoles 19 and 20 by CuAAC
Scheme 8. Alternative synthesis of 1,4-cDTs from propiolic acid and bisazide 25
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(Scheme 5) but symmetrical bistriazole 41 was completely different (Table S1; see SI) from
the symmetrical bistriazole 28 obtained from the reaction of vinyl sulfone 7 and diazide 25
(Scheme 5). This comparison unambiguously established that 28 was made of two 1,5-cDT
units. However, it should be noted that the chemical shift values of C5 for the 1,4-cDT unit of
27 was 127.5 ppm as opposed to the 138.0 ppm for C4 of its the 1,5-cDT unit; this was also
in line with prediction that the C5 signal of 1,4-DT appears is smaller (δ ∼120 ppm) than the
C4 signal of 1,5-DT (δ ∼133 ppm)13b provided both the regioisomers are available for
comparison. For the Δ(δC4−δC5) values of all mono- and bistriazoles 30-34 (Scheme 6),
similar confusion persisted (Table 1). Therefore, a CuAAC mediated reaction was carried
out with methyl propiolate 36a and diazide 29a; the reaction afforded the expected 1,4-cDTs,
namely 30a and 32a in 56%, and 18% yields respectively along with the unexpected 1,5-cDT
31a in 4% yield (Scheme 9). A direct comparison of the NMR data of these products and
triazoles obtained from vinyl sulfone 7 in scheme 6 unambiguously established the structures
of monomeric 1,4- cDTs. A comparison of 13C chemical shifts of regioisomers 30a/31a and
30b/31b revealed that C5 chemical shifts of 1,4-cDTs 30a/31a (128.8/128.9) were smaller
than those of the C4 chemical shifts of 1,5-cDTs 30b/31b (137.8/137.9) as suggested.13b The
structure of 33a was unambiguously established by reacting 31a, obtained from vinyl sulfone
7, with 36 followed by the methylation of the carboxylate 38 which afforded 33a (Scheme 9).
Once again, the chemical shift values of C5 (128.8) for the 1,4-cDT unit of 33a was smaller
than the same of C4 (137.9) of the 1,5-cDT unit. Similar analytical arguments were applied
to identify the structures 30b-34b obtained from the diazide 29b. The structure of
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symmetrical 1,5-cDT bistriazole 34b was easily assigned by comparing its 13C data with
those of the monomeric 1,5-cDT 30b (Table S1; see SI). It should be noted that symmetrical
and unsymmetrical bistriazoles can also be identified on the basis of the number of methylene
carbons in the 13C-NMR spectra of these compounds where all symmetrical bistriazoles
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generated only two sets of methylene carbons as opposed to four methylene carbons of the
unsymmetrical triazoles (Table S1; see SI).
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Scheme 9. Alternative synthesis of mono- and bistriazoles from propiolic acid and bisazide
29a.
CONCLUSION
An efficient and general metal-free route to afford 4-carboxylate-substituted 1,4-disubstituted
1,2,3-triazoles has been accomplished. The methodology follows a [3+2]-cycloaddition
reaction of methylcarboxylate-substituted vinyl sulfone with a wide range of organic azides.
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4-Carboxylated 1,4-disubstituted 1,2,3-triazoles containing free alcohol, acid, Boc-protected
amine, ester, protected sugars, long chain alkanes, benzyl, 9-methylanthracenyl and
cholesteryl units were isolated in good yields. Diazides also reacted under the reaction
conditions but afforded mixtures of products some of which were identified to have
unexpected 1,5-cDT units. The isolation of these 1,5-cDTs from the diazides, even under
CuAAC conditions warrants further investigation on the reaction mechanism with organic
diazides and other polyazides. Detailed analysis of NMR data along with the alternative
synthesis of triazoles unambiguously established the structures of triazoles. This study also
highlights the fact that in the case of synthesis of single regioisomeric 1,2,3-triazoles with
electron withdrawing groups caution must be taken in structural elucidation.
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EXPERIMENTAL SECTION
General procedure: Melting points were determined in open-end capillary tubes and are
uncorrected. All fine chemicals were obtained from commercial suppliers and were used
without further purification if otherwise not mentioned. TLC was carried out on pre-coated
silica plates (Merck silica gel 60, f254) and the visualization was obtained with UV light
and/or by charring the plate dipped in 5% H2SO4-MeOH and/or 5% H2SO4-vanilline and/or
ninhydrin solution. Oil bath was used for all reactions performed at elevated temperatures.
Flash column chromatography was performed on silica gel 230-400 mesh. 1H and 13C spectra
were recorded at 400 and 100 MHz respectively using CDCl3 as the solvent, unless
mentioned otherwise. Tetramethylsilane (TMS) was used as internal standard, and the
multiplicities were marked as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet) and
bs (broad singlet). DEPT experiments were carried out to identify methylene carbons and
quaternary carbons. HRMS measurements were carried out using Q-TOF.
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(E)-Methyl 3-tosyl acrylate 7. Compound 7 was synthesized by modifying the previously
reported procedure.10c A suspension of 2,3-dibromopropionic acid (5.0 g, 21.56 mmol) and
sodium p-toluenesulfinate (5.76 g, 32.34 mmol) in DMF (10 mL) was heated at 80 oC for 2
hours. The reaction mixture was allowed to cool at room temperature and diluted with EtOAc
(100 mL), followed by ice-cold water (30 mL). The organic layer was separated and washed
with cold water (3 x 30 mL), brine (30 mL), and water (30 mL); it was dried over anhyd.
Na2SO4, filtered and the filtrate was concentrated under reduced pressure to obtain a reddish
brown residue (compound 9). The crude material was used directly for the next step without
further purification. To a well-stirred solution of the crude residue in dry DCM (50 mL),
DBU (6 mL, 40.15 mmol) was added at 0 oC. MeI (3.4 mL, 54.61 mmol) was added drop-
wise over a period of 15 minutes at 0 oC under N2 atmosphere. After completion of the
addition, the reaction mixture was stirred at room temperature for 5 h. The reaction mixture
was poured into aq. satd. NaHCO3 solution and the product was extracted with DCM (3 x 30
mL). The combined organic layers were dried over anhyd. Na2SO4, filtered, and the filtrate
was concentrated under reduced pressure to obtain a reddish gummy residue. The residue was
purified over silica gel column to afford compound 7 (3.93 g, 76% over two steps). [Eluent:
1:9 = EtOAc:Hexane]. White crystalline solid. m. p. 107 oC-110 oC.
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General procedure for the reactions of vinyl sulfone 7 with monoazides and diazides: A well-
stirred solution of vinyl sulfone 7 (240 mg, 1 mmol) and an organic azide (1 mmol for
monoazides and 0.5 mmol for diazides) in DMSO (2 mL) was heated at 100 oC. On
completion (TLC), water (15 mL) was added to the reaction mixture and the organic
compounds were extracted with EtOAc (3 x 10 mL). Organic layers were pooled, washed
with saturated aq. NaHCO3 solution (2 x 10 mL), dried over anhyd. Na2SO4, filtered, and the
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filtrate was concentrated under reduced pressure. The residue, thus obtained was purified
over silica gel using the appropriate mixture of EtOAc and pet. ether as the eluent.
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Methyl 5-deoxy-5-{4-(methoxycarbonyl)-1H-1,2,3-triazol-1-yl}-2,3-O-isopropylidene-β-
D-Ribofuranoside 11. Following the general procedure 7 (120 mg, 0.5mmol) afforded
triazole 11 (117 mg, 75%) as a white crystalline solid [Eluent: EtOAc: pet ether (1:1)]; m.p.
126 - 128 °C.1H NMR:  8.21 (s, 1H), 4.99 (s, 1H), 4.43-4.73 (m, 5H), 3.93 (s, 3H), 3.35 (s,
3H), 1.43 (s, 3H), 1.28 (s, 3H). 13C{1H}NMR:  161.1 (C), 140.1 (C), 128.0 (CH), 113.1 (C),
110.2 (CH), 85.0 (CH), 84.9 (CH), 81.6 (CH), 55.8 (CH3), 53.5 (CH2), 52.2 (CH3), 26.4
(CH3), 24.9 (CH3). HRMS-ESI (m/z): [M + H]+ calcd for C13H20N3O6, 314.1352; found:
314.1356.
Methyl 1-benzyl-1H-1,2,3-triazole-4-carboxylate 12.12a Following the general procedure 7
(240 mg, 1 mmol) afforded triazole 12 (152 mg, 70%) as a white crystalline solid [Eluent:
EtOAc:pet ether (4:1)]; m.p.100-102 °C, lit.12a 99-102 oC. 1H NMR:  7.99 (s, 1H), 7.35- 7.36
(m, 3H), 7.25-7.27 (m, 2H), 5.55 (s, 2H), 3.88 (s, 3H). 13C{1H} NMR:  161.1 (C), 140.2 (C),
133.7 (C), 129.3 (CH), 129.1 (CH), 128.3 (CH), 127.5 (CH), 54.5 (CH2), 52.2 (CH3).
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Scaled-up synthesis of 12. A well-stirred solution of vinyl sulfone 7 (1.25 g, 5.1 mmol) and
benzyl azide (0.68 g, 5.1 mmol) in DMSO (5 mL) was heated at 100 oC for 30 h. The reaction
was quenched with aq. satd. NaHCO3 solution. After usual work-up (see general procedure),
the residue was purified over silica gel column to obtain triazole 12 (0.83 g, 73%) as a white
crystalline solid identical to the above compound.
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Methyl 1-undecyl-1H-1,2,3-triazole-4-carboxylate 13. Following the general procedure 7
(240 mg, 1 mmol) afforded triazole13 (227 mg, 77%) as white crystalline solid [Eluent:
EtOAc: pet ether (4:1)]; m.p. 73-75 °C. 1H NMR:  8.06 (s, 1H), 4.32 (t, J =7.2 Hz, 2H), 3.81
(s, 3H), 1.82 (d, J = 4.8 Hz, 2H), 1.13-1.20 (m, 18H), 0.75 (t, J= 6.8 Hz, 3H). 13C{1H} NMR:
 161.1(C), 139.7 (C), 127.4 (CH), 52.0 (CH3), 50.6 (CH2), 31.8 (CH2), 30.1 (CH2), 29.5
(CH2), 29.4 (CH2), 29.2 (3 CH2), 28.8 (CH2), 26.2 (CH2), 22.6 (CH2), 14.0 (CH3).HRMS-ESI
(m/z): [M + H]+ calcd for C16H30N3O2, 296.2338; found: 296.2339
Methyl 1-(2-ethoxy-2-oxoethyl)-1H-1,2,3-triazole-4-carboxylate 14.14b Following the
general procedure 7 (240 mg, 1 mmol) afforded triazole 14 (134 mg, 63%) as a white
crystalline solid [Eluent: EtOAc: pet ether (4:1)]; m.p. 104-106 °C, lit.14b 102-104 oC. 1H
NMR:  8.27 (s, 1H). 5.21 (s, 2H), 4.21 (q, J= 7.2 Hz, 2H), 3.89 (s, 3H), 1.24 (t, J= 6.8 Hz,
3H). 13C{1H} NMR:  165.8 (C), 160.9 (C), 140.1 (CH), 129.2 (CH), 62.7 (CH2), 52.2 (CH3),
51.0 (CH2), 14.0 (CH3).
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Methyl 1-(2-hydroxyethyl)-1H-1,2,3-triazole-4-carboxylate 15. Following the general
procedure 7 (240 mg, 1 mmol) afforded triazole 15 (123 mg, 72%) as a white crystalline solid
[Eluent: EtOAc: pet ether (2:1)]; m.p. 82-83 °C. 1H NMR:  8.23 (s, 1H), 4.49 (t, J = 4.4 Hz,
2H), 4.02 (d, J = 4.4 Hz, 2H), 3.83 (s, 3H). 13C{1H} NMR:  161.1 (C), 139.1 (C), 128.9
(CH), 60.5 (CH2), 53.2 (CH2), 52.2 (CH3). HRMS-ESI (m/z): [M + H]+ calcd for C6H10N3O3,
172.0722; found: 172.0725.
Methyl 1-[2-{(tert-butoxycarbonyl)amino}ethyl]-1H-1,2,3-triazole-4-carboxylate 16.
Following the general procedure, 7 (240 mg, 1 mmol) afforded triazole 16 (170 mg, 63%) as
a white crystalline solid [Eluent: EtOAc: pet ether (1:1)]; m.p. 110 - 115 °C. 1H NMR:  8.11
(s, 1H), 5.15 (br. s, 1H), 4.52 (s, 2H), 3.89 (s, 3H), 3.61 (d, J= 4.8 Hz, 2H), 1.37 (s, 9H).
13C{1H}NMR:  161.0 (C), 155.9 (C), 139.8 (C), 128.3 (CH), 80.1 (C), 52.0 (CH3), 50.2
(CH2), 40.5 (CH2), 28.23 (CH3 x 3). HRMS-ESI (m/z): [M + H]+ calcd for C11H19N4O4,
271.1406; found: 271.1408.
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5-{4-(Methoxycarbonyl)-1H-1,2,3-triazol-1-yl}pentanoic acid 17. Following the general
procedure vinyl sulfone 7 (240 mg, 1 mmol) afforded triazole 17 (163 mg, 72%) as a white
solid [Eluent: EtOAc]; m.p. 135 - 136 °C.1H NMR: 8.11 (s, 1H), 4.45 (t, J = 7.2 Hz, 2H),
3.95 (s, 3H), 2.42 (t, J= 7.2 Hz, 2H), 2.02 (quint., J= 7.6 Hz., 2H), 1.67 (t, J = 7.2 Hz, 2H).
13C{1H}NMR:  176.8 (C), 161.2 (C), 140.0 (C), 127.4 (CH), 52.3 (CH3), 50.3 (CH2), 32.7
(CH2), 29.3 (CH2), 21.4 (CH2).HRMS-ESI (m/z): [M + H]+ calcd for C9H14N3O4, 228.0984;
found: 228.0984.
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Methyl 1-{(2,2-dimethyl-1,3-dioxolan-4-yl)methyl}-1H-1,2,3-triazole-4-carboxylate 18.
Following the general procedure, 7 (240 mg, 1 mmol) afforded triazole 18 (169 mg, 70%) as
a white crystalline solid [Eluent: EtOAc: pet ether (4:1)]; m.p. 119 - 122 °C.1H NMR:  8.23
(s, 1H), 4.60-4.62 (m, 1H), 4.41-4.46 (m, 2H), 4.09-4.13 (m, 1H), 3.92 (s, 3H), 3.69-3.73 (m,
1H), 1.35 (s, 3H), 1.30 (s, 3H). 13C{1H}NMR:  161.1 (C), 139.9 (C), 128.9 (CH), 110.4 (C),
73.7 (CH), 66.2 (CH2), 52.6 (CH2), 52.2 (CH3), 26.7 (CH3), 25.1 (CH3).HRMS-ESI (m/z): [M
+ H]+ calcd for C10H16N3O4, 242.1141; found: 242.1142.
Methyl 1-(anthracen-9-yimethyl)-1H-1,2,3-triazole-4-carboxylate 19. Following the
general procedure, 7 (240 mg, 1 mmol) afforded triazole 19 (241 mg, 76%) as a yellow
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crystalline solid [Eluent: EtOAc: pet ether (4:1)]; m.p. 138 - 141 °C. 1H NMR:  8.64 (s, 1H),
8.24 (d, J = 6.8 Hz, 2H), 8.12 (d, J = 6.8 Hz, 2H), 7.55- 7.65 (m, 5H), 6.61 (s, 2H), 3.83 (s,
3H). 13C{1H}NMR:  161.0 (C), 140.0 (C), 131.5 (C), 130.8 (C), 130.4 (CH), 129.6 (CH),
128.0 (CH), 127.1 (CH), 125.6 (CH), 122.5 (CH), 52.1 (CH3), 46.7 (CH2). HRMS-ESI (m/z):
[M + H]+ calcd for C19H16N3O2, 318.1243; found: 318.1246.
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Methyl 4-deoxy-4-{4-(methoxycarbonyl)-1H-1,2,3-triazol-1-yl}-2,3-O-dibenzyl-5-O-
benzoyl--D-galactopyranoside 20. Following the general procedure, 7 (100 mg, 0.42
mmol) afforded triazole 20 (149 mg, 61%) as a white solid [Eluent: EtOAc: pet ether (2:3)];
m.p. 117 - 119 °C. 1H NMR:  8.30 (s, 1H), 7.94 (d, J = 8 Hz, 2H), 7.57 (t, J = 7.6 Hz, 1H),
7.43 (t, J = 7.6 Hz, 2H), 7.27-7.32 (m, 10H), 5.39-5.41 (m, 1H), 4.77-4.85 (m, 3H), 4.56-4.67
(m, 3H), 4.20-4.29 (m, 2H), 3.98-4.01 (m, 4H), 3.82-3.83 (m, 1H), 3.43 (s, 3H).
13C{1H}NMR:  165.8 (C), 161.1 (C), 140.1 (C), 137.8 (C), 137.2 (C), 133.4 (CH), 129.7
(CH), 129.2 (C), 128.5 (CH), 128.3 (CH), 128.2 (CH), 128.1 (CHx2), 89.9 (CH), 75.3 (CH),
74.8 (CH), 74.1 (CH2), 72.6(CH2), 65.4 (CH), 62.4 (CH3), 60.7 (CH), 55.8 (CH3), 52.1 (CH3).
HRMS-ESI (m/z): [M + H]+ calcd for C32H34N3O8, 588.2346; found: 588.2369.
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6-deoxy-6-{4-(methoxycarbonyl)-1H-1,2,3-triazol-1-yl}-1,2-O-isopropylidine-3,5-O-
dibenzyl--D-glucofuranoside 21.Following the general procedure, 7 (100 mg, 0.42 mmol)
afforded triazole 21 (142 mg, 67%) as a pale yellow gum [Eluent: EtOAc: pet ether (1:1)]. 1H
NMR:  8.16 (s, 1H), 7.24-7.34 (m, 8H), 7.10-7.13 (m, 2H), 5.93 (d, J = 3.6 Hz, 1H), 4.94
(dd, J =12 Hz and 4 Hz, 1H), 4.64-4.67 (m, 2H), 4.41-4.52 (m, 3H), 4.34 (d, J = 11.2 Hz,
1H), 4.19-4.23 (m, 1H), 4.03 (d, J = 3.2 Hz, 1H), 3.98 (dd, J = 8 Hz and 4 Hz, 1H), 3.90 (s,
3H), 1.43 (s, 3H), 1.31 (s, 3H). 13C{1H}NMR:   (C), 139.7 (C), 137.1 (C), 137.0 (C),
129.1 (CH), 128.6 (CH), 128.5 (CH), 128.2 (CH), 128.0 (CH), 127.8 (CH), 112.2 (C), 104.9
(CH), 81.6 (CH), 81.2 (CH), 79.1 (CH), 74.0 (CH), 72.4 (CH2), 71.9 (CH2), 52.0 (CH3), 51.1
(CH2), 26.7 (CH3), 26.3 (CH3). HRMS-ESI (m/z): [M + H]+ calcd for C27H32N3O7, 510.2240;
found: 510.2218
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2-{4-(M vethoxycarbonyl)-1H-1,2,3-triazol-1-yl}-2,3,4,6-tetraacetyl--D-
glucopyranoside 22. Following the general procedure, 7 (100 mg, 0.42 mmol) afforded
triazole 22 (129 mg, 62%) as a pale yellow gum [Eluent: EtOAc: pet ether (1:1)]. 1H NMR:
 8.08 (s, 1H), 5.08 (t, J = 9.2 Hz, 1H),4.93 (td, J = 32 Hz and 8 Hz, 2H), 4.60-4.63 (m, 1H),
4.51-4.53 (m, 1H), 4.44 (d, J = 8 Hz, 1H), 4.12-4.19 (m, 2H), 4.04 (d, J = 12 Hz, 1H), 3.86-
3.89 (m, 1H), 3.84 (s, 3H), 3.62-3.66 (m, 1H), 1.99 (s, 3H), 1.94 (s, 3H), 1.90 (s, 3H), 1.87 (s,
3H). 13C{1H}NMR: 170.5 (C), 170.0 (C), 169.3 (C), 161.0 (C), 139.7 (C), 128.8 (CH),
100.3 (CH), 72.4 (CH), 71.8 (CH), 70.9 (CH), 68.1 (CH), 67.4 (CH2), 61.6 (CH2), 52.1
(CH3), 50.3 (CH2), 20.6 (CH3), 20.5 (CH3 x 2), 20.4 (CH3). HRMS-ESI (m/z): [M + H]+ calcd
for C20H28N3O12, 502.1673; found: 502.1664.
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4-Methoxycarbonyl-1-(3)-cholest-5-en-3-yl-1H-1,2,3-triazole 23. Following the general
procedure, 7 (100 mg, 0.42 mmol) afforded triazole 23 (128 mg, 62%) as a white crystalline
solid [Eluent: EtOAc: pet ether (4:1)]; m.p. 133 - 135 °C. . 1H NMR:  8.30 (s, 1H), 5.54 (s,
1H), 4.97 (s, 1H), 3.95 (s, 3H), 2.99 - 3.03 (m, 1H), 2.52 - 2.55 (m, 1H), 1.12-2.27 (m, 20H),
1.10 (s, 3H), 0.93 - 1.07 (m, 6H), 0.91 (d, J = 6.0 Hz, 3H), 0.86 (d, J = 6.0 Hz, 6H), 0.68 (s,
3H). 13C{1H}NMR:  161.5 (C), 139.1 (C), 137.4 (C), 127.2 (CH), 125.1 (CH), 57.1 (CH),
56.5 (CH), 56.1 (CH), 52.1 (CH3), 50.0 (CH), 42.3 (C), 39.5 (CH2), 37.1 (C), 36.2 (CH2),
35.8 (CH), 35.4 (CH2), 32.5 (CH2), 31.9 (C), 31.7 (CH2), 28.2 (CH2), 28.0 (CH and CH2),
27.0 (CH2), 24.2 (CH2), 23.9 (CH2), 22.8 (CH3), 22.6 (CH3), 20.6 (CH2), 19.2 (CH3), 18.7
(CH3), 11.9 (CH3). HRMS-ESI (m/z): [M + H+ Na]+ calcd for C31H50N3O2Na, 519.3801;
found: 519.3776.
4-Methoxycarbonyl-1-[1-{2-((3)-cholest-5-en-3-yloxy}-ethyl}-1H-1,2,3-triazole 24.
Following the general procedure, 7 (100 mg, 0.42 mmol) afforded triazole 24 (160 mg, 71%)
as a white crystalline solid [Eluent: EtOAc: pet ether (4:1)]; m.p. 92 - 94 °C. 1H NMR: 
8.22 (s, 1H), 5.28 (d, J = 4.8 Hz, 1H), 4.54 (t, J = 4.8 Hz, 2H), 3.92 (s, 3H), 3.82 (t, J = 5.2
Hz, 2H), 3.05 - 3.11 (m, 1H), 2.52 - 2.55 (m, 1H), 0.97-2.27 (m, 27H), 0.95 (s, 3H), 0.87 (d, J
= 7.2 Hz, 3H), 0.83 (d, J = 6.4 Hz, 6H), 0.64 (s, 3H). 13C{1H}NMR:  161.3 (C), 140.2 (C),
139.7 (C), 128.7 (CH), 122.1 (CH), 79.8 (CH), 65.8 (CH2), 56.7 (CH), 56.1 (CH), 52.2
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(CH3), 51.1 (CH2), 50.1 (CH), 42.3 (C), 39.7 (CH2), 39.5 (CH2), 38.8 (CH2), 37.0 (CH2),
36.8 (CH2), 36.2 (CH2), 35.8 (CH), 31.9 (CH2), 31.8 (CH), 28.2 (CH2), 28.0 (CH), 24.3
(CH2), 23.8 (CH2), 22.8 (CH3), 22.6 (CH3), 21.0 (CH2), 19.3 (CH3), 18.7 (CH3), 11.8
(CH3).HRMS-ESI (m/z): [M + H]+ calcd for C33H54N3O3, 540.4165; found: 540.4167.
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Methyl 1-(4-azidobutyl)-1H-1,2,3-triazole-4-carboxylate 26. Following the general
procedure, 7 (240 mg, 1 mmol) afforded triazole 26 (38 mg, 17%) as a colourless gum
[Eluent: EtOAc: pet ether (1:3)]. 1H NMR:  8.12 (s, 1H), 4.40 (t, J = 7.2 Hz, 2H), 3.84 (s,
3H), 3.26 (t, J = 6.4 Hz, 2H), 1.96 (quint., J = 6.8 Hz, 2H), 1.52 (quint., J = 6.8 Hz, 2H).
13C{1H}NMR:  161.0 (C), 139.8 (C), 127.6 (CH), 52.0 (CH3), 50.6 (CH2), 50.0 (CH2), 27.3
(CH2), 25.7 (CH2). HRMS-ESI (m/z): [M + H]+ calcd for C8H13N6O2, 225.1100; found:
225.1106.
Methyl 1-[4-{5-(methoxycarbonyl)-1H-1,2,3-triazol-1-yl}butyl]-1H-1,2,3-triazole-4-
carboxylate 27. Following the general procedure, 7 (240 mg, 1mmol) afforded triazole 27
(102 mg, 33%) as a white amorphous solid [Eluent: EtOAc]; m.p. 78-80 oC. 1H NMR:  8.13
(s, 1H), 8.08 (s, 1H), 4.79 (t, J = 6.4 Hz, 2H), 4.46 (t, J = 6.4 Hz, 2H), 3.96 (s, 3H), 3.94 (s,
3H), 1.98 (t, J = 3.6 Hz, 4H). 13C{1H}NMR:  161.1 (C), 158.8 (C), 139.9 (C), 138.0 (CH),
127.6 (CH), 127.5 (C), 52.6 (CH3), 52.2 (CH3), 49.7 (CH2), 49.1 (CH2), 26.9 (CH2), 26.7
(CH2). HRMS-ESI (m/z): [M + H]+ calcd for C12H17N6O4, 309.1311; found: 309.1313.
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Dimethyl 1,1’-(butane-1,4-diyl)bis(1H-1,2,3-triazole-4-carboxylate) 28. Following the
general procedure, 7 (240 mg, 1 mmol) afforded triazole 28 (15 mg, 5%) as a colourless gum;
[Eluent: EtOAc: pet ether (1:1)]. 1H NMR:  8.11 (s, 2H). 4.77 (t, J = 6.4 Hz, 4H), 3.93 (s,
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6H), 1.94-1.97 (m, 4H). 13C{1H}NMR:  158.9 (C), 138.0 (CH), 127.5 (C), 52.5 (CH3), 49.4
(CH2), 26.8 (CH2). HRMS-ESI (m/z): [M + H]+ calcd for C12H17N6O4, 309.1311; found:
309.1318.
Methyl 1-{2-(2-azidoethoxy)ethyl}-1H-1,2,3-triazole-4-carboxylate 30a. Following the
general procedure, 7 (240 mg, 1 mmol) afforded triazole 30a (43 mg, 18%) as a colourless
gum; [Eluent: EtOAc: pet ether (1:1)]. 1H NMR:  8.24 (s, 1H), 4.61 (t, J= 4.8 Hz, 2H), 3.94
(s, 3H), 3.89 (t, J= 4.8 Hz, 2H), 3.61 (t, J = 4.8 Hz, 2H), 3.36 (t, J = 4.8 Hz, 2H).
13C{1H}NMR:  161.1 (C), 139.8 (C), 128.8 (CH), 70.1 (CH2), 69.0 (CH2), 52.1 (CH3), 50.6
(CH2), 50.5 (CH2). HRMS-ESI (m/z): [M + H]+ calcd for C8H13N6O3, 241.1049; found:
241.1048.
Methyl 1-[2-{N-(2-azidoethyl)-p-tolylsulfonamido}ethyl]-1H-1,2,3-triazole-4-carboxylate
30b. Following the general procedure, 7 (240 mg, 1 mmol) afforded triazole 30b (83 mg,
21%) as a pale yellow gum, [Eluent: EtOAc: pet ether (1:1)]. 1H NMR:  8.18 (s, 1H), 7.65
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(d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 4.71 (t, J = 6.4 Hz, 2H), 3.93 (s, 3H), 3.61 (t, J =
6.0 Hz, 2H), 3.30 (t, J = 6.0 Hz, 2H), 3.13 (t, J = 6.0Hz, 2H),  (s, 3H). 13C{1H}NMR:
 160.9 (C), 144.6 (C), 139.8 (C), 134.7 (C), 130.1 (CH), 128.9 (CH),127.3 (CH), 52.2
(CH3), 50.4 (CH2),50.1 (CH2), 49.7 (CH2), 49.5 (CH2), 21.6 (CH3). HRMS-ESI (m/z): [M +
H]+ calcd for C15H20N7O4S, 394.1297; found: 394.1295.
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Methyl 1-{2-(2-azidoethoxy)ethyl}-1H-1,2,3-triazole-5-carboxylate 31a. Following the
general procedure, 7 (240 mg, 1 mmol) afforded triazole 31a (19 mg, 8%) as a colourless
gum; [Eluent: EtOAc: pet ether (1:3)]. 1H NMR (400 MHz, CDCl3):  8.12 (s, 1H), 4.97 (t, J
= 5.6 Hz, 2H), 3.93- 3.97 (m, 2H), 3.92 (s, 3H), 3.60 (t, J = 4.8 Hz, 2H), 3.30 (t, J = 4.8 Hz,
2H). 13C{1H}NMR:  159.0 (C),137.8 (CH), 128.3 (C), 69.9 (CH2), 69.3 (CH2), 52.5 (CH3),
50.6 (CH2), 49.4 (CH2). HRMS-ESI (m/z): [M + H]+ calcd for C8H13N6O3, 241.1049; found:
241.1049.
Methyl 1-[2-{N-(2-azidoethyl)-p-tolylsulfonamido}ethyl]-1H-1,2,3-triazole-5-carboxylate
31b. Following the general procedure, 7 (240 mg, 1 mmol) afforded triazole 31b (35 mg, 9%)
as a pale yellow gum, [Eluent: EtOAc: pet ether (1:1)]. 1H NMR:  8.08 (s, 1H), 7.66 (d, J =
8.0 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 4.94 (t, J = 6.8 Hz, 2H), 3.94 (s, 3H), 3.66 (t, J = 6.8
Hz, 2H), 3.50 (t, J = 6.0 Hz, 2H),  (t, J = 6.0 Hz, 2H), 2.41 (s, 3H). 13C{1H}NMR:
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 158.9 (C),144.1 (C), 137.9 (CH), 135.6 (C), 130.0 (CH), 127.9 (C), 127.3 (CH), 52.7
(CH3), 50.5 (CH2), 48.8 (CH2), 48.7 (CH2), 48.3 (CH2), 21.5 (CH3). HRMS-ESI
(m/z): [M + H]+ calcd for C15H20N7O4S, 394.1297; found: 394.1312.
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Dimethyl 1,1’-{oxybis(ethane-2,1-diyl)}bis(1H-1,2,3-triazole-4-carboxylate) 32a.
Following the general procedure, 7 (240 mg, 1mmol) afforded triazole 32a (110 mg, 34%) as
a white crystalline solid; m. p. 110-111 oC, [Eluent: EtOAc]. 1H NMR:  8.04 (s, 2H), 4.56 (t,
J= 4.8 Hz, 4H), 3.96 (s, 6H), 3.88 (t, J = 4.8 Hz, 4H). 13C{1H}NMR:  161.0 (C), 140.0 (C),
128.3 (CH), 69.0 (CH2), 52.2 (CH3), 50.3 (CH2). HRMS-ESI (m/z): [M + H]+ calcd for
C12H17N6O5, 325.1260; found: 325.1256.
Dimethyl 1,1’-{(tosylazanediyl)bis(ethane-2,1-diyl)}bis(1H-1,2,3-triazole-4-carboxylate)
32b. Following the general procedure, 7 (240 mg, 1 mmol) afforded triazole 32b (181 mg,
38%) as a white amorphous solid. [Eluent: EtOAc]; m.p. 134- 138 oC. 1H NMR:  8.04 (s,
2H), 7.64 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 4.46 (t, J = 6.4 Hz, 4H), 3.96 (s, 6H),
3.53 (t, J =6.4 Hz, 4H), 2.45 (s, 3H). 13C{1H}NMR:  160.8 (C),145.1 (C), 140.1 (C), 130.3
(CH), 128.7 (CH), 127.4 (CH), 52.3 (CH3), 50.0 (CH2),49.5 (CH2), 21.6 (CH3). HRMS-ESI
(m/z): [M + H]+ calcd for C19H24N7O6S, 478.1509; found: 478.1501.
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Methyl 1-[2-{2-(5-(methoxycarbonyl)-1H-1,2,3-triazol-1-yl)ethoxy}ethyl]-1H-1,2,3-
triazole-4-carboxylate 33a. Following the general procedure, 7 (240 mg, 1 mmol) afforded
triazole 33a (36 mg, 11%) as a colourless gum, [Eluent: EtOAc]. 1H NMR:  8.08 (s, 1H),
8.00 (s, 1H), 4.90 (t, J = 5.2 Hz, 2H), 4.49 (t, J = 5.2 Hz, 2H), 3.87-3.96 (m, 8H), 3.80 (t, J =
4.8 Hz, 2H). 13C{1H}NMR:  161.1 (C), 159.0 (C), 139.9 (C), 137.9 (CH), 128.6 (CH), 128.0
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(C), 69.2 (CH2), 68.7 (CH2), 52.6 (CH3), 52.1 (CH3),  (CH2),  (CH2). HRMS-ESI
(m/z): [M + H]+ calcd for C12H17N6O5, 325.1260; found: 325.1263.
Methyl 1-[2-{N-(-(5-(methoxycarbonyl)-1H-1,2,3-triazol-1-yl)ethyl)-4-
tolylsulfonamido}ethyl]-1H-1,2,3-triazole-4-carboxylate 33b. Following the general
procedure, 7 (240 mg, 1 mmol) afforded triazole 33b (38 mg, 8%) as a pale yellow gum,
[Eluent: EtOAc]. 1H NMR:  8.17 (s, 1H), 8.06 (s, 1H), 7.59 (d, J = 8.0 Hz, 2H), 7.28 (d, J =
8.0 Hz, 2H), 4.69 (q, J = 6.4 Hz, 4H), 3.93 (s, 3H), 3.92 (s, 3H), 3.69 (t, J = 6.4 Hz, 2H), 3.51
(t, J = 6.8 Hz, 2H), 2.41 (s, 3H). 13C{1H}NMR):  160.9 (C), 158.9 (C), 144.5 (C), 139.9 (C),
137.9 (CH), 134.8 (C), 130.1 (CH x 2), 128.8 (CH), 127.9 (C), 127.3 (CH), 52.8 (CH3), 52.2
(CH3), 49.8 (CH2), 49.0 (CH2 x 2), 48.4 (CH2), 21.5 (CH3). HRMS-ESI (m/z): [M + H]+ calcd
for C19H24N7O6S, 478.1509; found: 478.1522.
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