Synthesis and photophysical properties of fluorescent 2,1,3- benzothiadiazole-triazole-linked glycoconjugates: Selective chemosensors for Ni(II)

Article abstract of DOI:10.1016/j.tet.2012.10.043

The synthesis of new fluorescent 2,1,3-benzothiadiazole-triazole-linked glycoconjugates is described by a straightforward synthetic route, using a copper(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (CuAAC). UV-visible (UV-vis) and steady-state fluorescence in solution were applied in order to characterize its photophysical behavior. The dyes present absorption in the violet region with fluorescence emission in the cyan-green region, which can be related to the methoxy derivatives due to an intramolecular charge transfer (ICT) in the excited state. The studied derivatives present potential optical application since combine large extinction coefficient for absorption, large Stokes shift and high fluorescence emission. Additionally, these dyes exhibit binding selectivity to Ni⁺² among a series of cations in CH ₃CN solution.

Full text of DOI:10.1016/j.tet.2012.10.043

Tetrahedron 69 (2013) 201e206
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis and photophysical properties of fluorescent
2,1,3-benzothiadiazole-triazole-linked glycoconjugates:
selective chemosensors for Ni(II)
*
ꢀ
Angelica V. Moro , Patrícia C. Ferreira, Pedro Migowski, Fabiano S. Rodembusch, Jairton Dupont,
*
€
Diogo S. Ludtke
Instituto de Química, Universidade Federal do Rio Grande do Sul, UFRGS, Av. Bento Gonc¸ alves 9500, 91501-970 Porto Alegre, RS, Brazil
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of new fluorescent 2,1,3-benzothiadiazole-triazole-linked glycoconjugates is described by
a straightforward synthetic route, using a copper(I)-catalyzed azideealkyne 1,3-dipolar cycloaddition
(CuAAC). UVevisible (UVevis) and steady-state fluorescence in solution were applied in order to char-
acterize its photophysical behavior. The dyes present absorption in the violet region with fluorescence
emission in the cyan-green region, which can be related to the methoxy derivatives due to an intra-
molecular charge transfer (ICT) in the excited state. The studied derivatives present potential optical
application since combine large extinction coefficient for absorption, large Stokes shift and high fluo-
rescence emission. Additionally, these dyes exhibit binding selectivity to Niþ2 among a series of cations in
CH3CN solution.
Received 11 September 2012
Received in revised form 10 October 2012
Accepted 15 October 2012
Available online 23 October 2012
Keywords:
Fluorescence
Benzothiadiazoles
Glycoconjugates
Chemosensors
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
chemistry concept.11 Sugar-derived triazoles have been the subject
of intense research in recent years, mainly due to the reluctance of
Benzothiadiazolyl derived molecules are widely investigated
nowadays due totheir well-knownphotophysical properties such as
high extinction coefficient, intense fluorescence, and large Stokes
shift.1 These features make them useful in a variety of applications
such as optical materials and chemosensors.2 Fluorescent 2,1,3-
benzothiadiazole (BTD) derivatives have been described as useful
dyes with a number of applications in metal,3 protein,4 and DNA5
detection, as live cell-imaging probes6 and dyes for real-time PCR.7
On the other hand, carbohydrates are naturally available mole-
cules, which constitute the largest part of biomass produced by
living organisms and therefore are abundant and inexpensive. In
addition, carbohydrates present low toxicity and are polyfunctional
molecules with varied scaffolds. These attractive features can be
used for the design of functional molecules with available sites for
metal coordination. In particular, glycoconjugation would be
a promising approach for the synthesis of chiral fluorescent mol-
ecules with many potential applications as chemosensors.8 One
method of choice for an efficient glycoconjugation is the copper(I)-
catalyzed azideealkyne 1,3-dipolar cycloaddition reaction
(CuAAC),9,10 which is the best known example of the click
the triazole linker to undergo hydrolysis, oxidation, and reduction
in the biological environment. In addition, its ability to participate
in hydrogen-bonding and dipole interactions has attracted the at-
tention of synthetic carbohydrate chemists, medicinal chemists as
well as materials chemists.12 The click chemistry approach for
fluorescent labeling of biomolecules has been applied for proteins
functionalized with an alkyne or azide group13 as well as for amino
acids.14 In connection with our recent interest on the use of car-
bohydrates as a chiral pool for the synthesis of chiral molecules,15
we hypothesized if it would be possible to efficiently introduce
a fluorescent group within the sugar framework. A straightforward
approach to this aim would be the CuAAC between sugar azides and
a fluorescent BTD derivative bearing an alkyne moiety (Scheme 1).
The resulting molecules would possess several coordinating atoms
and might be used as fluorescent probes for the detection of metals
in solution, since many sites would be available for metal
coordination.
* Corresponding authors. Tel./fax: þ55 51 3308 7201; e-mail addresses:
Scheme 1. General approach for the synthesis of BTD-triazole-glycoconjugates.
€
angelventurini@gmail.com (A.V. Moro), dsludtke@iq.ufrgs.br (D.S. Ludtke).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.10.043

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A.V. Moro et al. / Tetrahedron 69 (2013) 201e206
Herein we report our results on the synthesis of BTD-triazole-
linked glycoconjugates through a Cu(I)-catalyzed alkyneeazide
cycloaddition, their photophysical properties, and their application
as fluorescent probes for the selective detection of nickel(II).
2. Results and discussion
Initially, we prepared the sugar azides 2 and 4 in an efficient
sequence, starting from
D
-xylose and
D-galactose as the starting
sugars. First,
D
-xylose was treated with acetone in the presence of
catalytic amounts of iodine,16 followed by partial deprotection to
afford the corresponding diol. Selective reaction of the primary
hydroxyl group with TsCl in pyridine resulted in the tosylate 1,
which was subjected to reaction with NaN3 to afford the desired
azide 217 in 57% overall yield over three steps (Scheme 2).
Scheme 4. Synthesis of alkynes 6 and 7.
decomposition of the resulting terminal alkynes. Indeed, even the
protected alkynes 6 and 7 have limited stability and should be
prepared and immediately used in the CuAAC reaction.
With the required starting materials in hands, the cycloaddition
reactions were performed. Gratifyingly, reaction of sugar azide 2
with BTDealkynes 6 and 7, under copper catalysis, in the presence
of sodium ascorbate and TBAF, smoothly resulted in the BTD-
triazole-glycoconjugates 8 and 9 in excellent yields (89 and 94%,
respectively) (Scheme 5).
Scheme 2. Synthesis of azide 2.
Following the same strategy,
D-galactose was submitted to
protection of the hydroxyl groups as the corresponding acetonides,
followed by tosylation of the free primary alcohol to afford tosylate
3. A clean substitution reaction with sodium azide delivered the
corresponding azide 418 in 60% yield over the three-step sequence
(Scheme 3).
Scheme 5. CuAAC with azide 2.
Scheme 3. Synthesis of azide 4.
It is worth to note that the sequences delineated above are very
efficient and have been carried out in gram-scale, allowing the fast
synthesis of significant amounts of azides 2 and 4. Next, BTD
dibromide 5 was converted to the TMS-protected alkynes 6 and 7,
by palladium-catalyzed reactions (Scheme 4). When 5 was sub-
jected to Suzuki coupling with 4-methoxyphenylboronic acid, in
the presence of catalytic amounts of the non-symmetrical NCP
pincer palladacycle (NCPePd),19 the arylated product was formed
Similarly, reaction of BTDealkynes 6 and 7 with the galactose-
derived azide 4 afforded both the unsymmetrical and symmetri-
cal the 1,2,3-triazolyl glycoconjugates 10 and 11 very efficiently and
the products were isolated in 87 and 91% yields, respectively
(Scheme 6).
With an efficient synthesis of the BTD-triazole-glycoconjugates
established, their photophysical properties were examined. The
absorption and emission spectra of the dyes 8e11 in 1,4-dioxane
are shown in Fig. 1.
in 85% yield. Subsequently,
a
Sonogashira reaction with
TMSeacetylene, catalyzed by PdCl2(PPh3)2 afforded the un-
symmetrical alkyne 6. On the other hand, a direct double Sonoga-
shira reaction using 2 equiv of TMSeacetylene resulted in the
symmetrical alkyne 7 in 95% yield (Scheme 4).
The dyes 8e11 present absorption bands at the same region,
indicating that the additional triazolyl moiety does not play a fun-
damental role on the electronic conjugation in the ground state of
the dyes. The lowest energy absorption bands are in agreement
Importantly, attempts to obtain alkynes 6 and 7 in their
deprotected forms were unsuccessful, due to the fast
with
p
/
p
*
transitions due to their large molar extinction co-
max). The relevant data are summarized in Table 1.
efficient values (
3

A.V. Moro et al. / Tetrahedron 69 (2013) 201e206
203
Table 2
Fluorescence and excitation data of the dyes 8e11, where lexc is the excitation
maximum in nanometers, lem is the fluorescence emission maximum in nanome-
ters, ffl is the fluorescence quantum yield, and DlST is the Stokes shift in nanometers
(cmꢀ1
)
a
Dye
Solvent
lexc
lem
DlST
ffl
8
Ethanol
Acetonitrile
1,4-Dioxane
415
415
424
547
541
523
143(6470.9)
137(6268.2)
113(5269.8)
0.126
0.286
0.289
9
Ethanol
Acetonitrile
1,4-Dioxane
409
414
421
508
509
508
112(5567.5)
107(5229.3)
97(4645.9)
0.436
0.502
0.406
10
Ethanol
Acetonitrile
1,4-Dioxane
417
416
423
544
542
524
146(6743.3)
139(6363.7)
112(5187.9)
0.489
0.561
0.447
11
Ethanol
Acetonitrile
1,4-Dioxane
411
415
423
508
509
508
104(5067.4)
105(5106.1)
97(4645.9)
0.137
0.288
0.342
Scheme 6. CuAAC with azide 4.
a
The Stokes shift was obtained from the difference of the emission and absorp-
lem labs).
tion maximum (DlST
¼
ꢀ
observe that the
p-conjugation has a significant effect on the
photophysical properties of these compounds, indicating that this
structural change is fundamental for the fluorescence itself. Evi-
dences of intramolecular charge transfer (ICT) in the excited state
could be observed to the derivatives 8 and 10, where a redshift
takes place increasing the solvent polarity, since the species with
charge separation (ICT state) may become the lowest energy
state.20 Additionally, the solvatochromic effect between the dyes 8
and 10 from 9 and 11, can also be rationalized concerning the dyes
structure, where it was already observed that as the symmetry of
the compound increases (compounds 9 and 11 possess a more
symmetric structure than 8 and 10) the excited state lowers, and
consequently there is less stabilization by the solvent dipoles.20b In
this way, as already observed in the literature, a very efficient
intramolecular charge transfer takes place in the excited state be-
tween the terminal methoxy group and the benzothiadiazole
nucleus.1
Fig. 1. Normalized absorbance and fluorescence emission of dyes 8e11 in 1,4-dioxane.
It is worth mentioning that the same photophysical behavior could
be observed in acetonitrile and ethanol (see Supplementary data).
The normalized fluorescence emission spectra of these dyes
were obtained using the absorption maxima as the excitation
wavelengths. The relevant data are summarized in Table 2. The
derivatives 8 and 10 present red shifted emission bands (w537 nm)
in despite of the dyes 9 and 11 (w508 nm). These results allowed to
From this analysis, although the acetonitrile presents higher
dielectric constant than ethanol, the observed emission maxima in
this protic polar solvent is due to the ability to present specific
interactions (hydrogen bonds) with these dyes.21 Large Stokes
shifts could be calculated for all studied dyes (w4600e6700 cmꢀ1).
Concerning the absence of a solvatochromic effect in derivatives 9
and 11, as well as the large Stokes shift for all dyes, the obtained
values cannot be related only to a charge transfer in the excited
state.1 The excitation spectra of the dyes 8e11 in different solvents
were recorded at different lem in the range of 300e520 nm and are
presented in Fig. 2. In each case, the fluorescence excitation spectra
resemble each other and also with the absorption spectra in the
respective solvent. The same small solvatochromic effect could be
observed. This suggests that there is only one species for the dyes
8e11 in the S0 state, although a better structuration could be ob-
served in the excitation spectra.
Table 1
UVevis data of the dyes 8e11, where labs is the absorption in nanometers and
3 is the
molar extinction coefficient in ꢁ104 Mꢀ1 cmꢀ1
Dye
Solvent
labs (l)
8
Ethanol
Acetonitrile
1,4-Dioxane
404(0.88), 320(0.84), 308(0.81), 273(2.20)
404(0.93), 320(0.81), 308(0.77), 273(2.22)
410(1.06), 321(1.08), 309(1.06), 273 (2.74)
9
Ethanol
Acetonitrile
1,4-Dioxane
396(0.87), 322(1.01), 308(0.78), 266(2.14)
402(0.95), 322(1.07), 308(0.78), 267(2.45)
411(1.02), 324(1.41), 310(1.08), 268(3.06)
To get insight into the binding properties of the dyes 8e11 to-
ward metal ions (Znþ2, Cdþ2, Coþ2, Mgþ2, Niþ2, and Agþ), it was
investigated the fluorescence profile of the dyes upon addition of
20 equiv of selected cations to the acetonitrile solution (Fig. 3). As
can be observed, the fluorescence emission was not affected by
Znþ2, Cdþ2, Agþ, and Mgþ2, slightly quenched by Coþ2 and signifi-
cantly quenched by Niþ2, as already observed in similar struc-
tures.22 It is worth mentioning that the same photophysical
behavior could be observed to the dyes 8, 10, and 11 (see
Supplementary data). Dyes 9e11 presented the higher decrease of
10
11
Ethanol
Acetonitrile
1,4-Dioxane
398(1.09), 321(1.20), 308(0.88), 267(2.60)
403(1.15), 321(1.21), 308(0.84), 267(2.88)
412(1.29), 324(1.56), 315(1.15), 310(1.13)
Ethanol
Acetonitrile
1,4-Dioxane
404(1.04), 320(1.02), 309(1.02), 275(2.63)
404(1.01), 320(0.88), 309(0.83), 273(2.47)
411(1.21), 322(1.23), 309(1.19), 275(3.14)

204
A.V. Moro et al. / Tetrahedron 69 (2013) 201e206
fluorescence emission upon addition of the Niþ2, with the dye 9
presenting the higher one.
Due to the better fluorescence response upon addition of the
metal, dye 9 was selected for detailed fluorescence assessments. In
acetonitrile solution, the addition of Niþ2 (from 0.06 to 5.75 equiv)
decreased gradually and finally reached its quenching plateau at
w6 equiv (Fig. 4). Regarding the results presented in the literature,
although the dye 9 does not present fluorescence response in the
higher range of metal concentration, the dye seems clearly be more
sensitive.22 On the other hand, the results in ethanol indicates that
the dye 9 is less sensitive, probably due to the solvent ability to
present hydrogen bond with the binding sites in the structure, al-
though an higher linear relation could be obtained (2.38ꢁ10ꢀ6 to
5.48ꢁ10ꢀ5 M). The additional fluorescence emission curves in
ethanol are presented in Supplementary data.
Fig. 2. Normalized excitation spectra of dyes 8e11 in 1,4-dioxane.
Fig. 4. Fluorescence spectra of dye 9 (8.14ꢁ10ꢀ6 M) upon addition of Niþ2 ion in
acetonitrile (top) and ethanol (bottom) (lex¼405 nm).
In both solvents, the fluorescence intensity is progressively
quenched with increasing concentration of Niþ2 (Fig. 4), as clearly
observed by the decrease of fluorescence intensity as a function of
the metal (inset), which can probably be related to a photoinduced
electron transfer (PET) or charge transfer (CT) mechanism.22,23
3. Conclusions
In summary, the synthesis of four new fluorescent triazolyl
glycoconjugates was accomplished through a copper(I)-catalyzed
azideealkyne cycloaddition between a sugar-derived azide and
a BTDealkyne. The synthesis is straightforward and delivers the
compounds in a short and efficient synthetic sequence. In addition,
Fig. 3. Fluorescence spectra of dye 9 upon addition of various NOꢀ3 salt (20 equiv) in
MeCN (lex¼405 nm).

A.V. Moro et al. / Tetrahedron 69 (2013) 201e206
205
photophysical studies revealed that the glycoconjugates 8e11
present absorption in the violet region with fluorescent emission in
the cyan-green region. The large extinction coefficient for absorp-
tion, large Stokes shift, and high fluorescence emission make this
molecules promising for optical applications. In addition, it was
shown that dyes 8e11 can be used as chemosensors exhibiting
strong selective binding to Niþ2 in acetonitrile solution.
and the crude product was filtered in a column of silica, concentrated
under reduced pressure, and immediately used in the next step.
4.4. General procedure for the CuAAC reaction
To a solution of alkynyl BTD 6 (0.5 mmol) and the azido sugar
(0.5 mmol), in dichloromethane (5 mL) and water (5 mL),
CuSO4$5H2O (13 mg, 0.05 mmol), sodium ascorbate (10 mg,
0.05 mmol) were added. Next, TBAF 1 M in THF (1 mL, 1 mmol) was
dropwise added. The reaction mixture was stirred at room tem-
perature for 24 h and washed with an EDTA solution 0.1 M (10 mL)
and then extracted with ethyl acetate (3ꢁ10 mL). The organic layer
was washed with a saturated aqueous solution of NaCl, dried under
MgSO4, filtered, and concentrated. The crude product was purified
by flash chromatography.
4. Experimental
4.1. General procedures
1H and 13C NMR spectra were recorded at 400 or 300 MHz and
100 or 75 MHz, respectively, with tetramethylsilane as internal
standard. High-resolution mass spectra were recorded on a Bruker
Daltonics Micro-TOF instrument in ESI-mode. Column chromatog-
raphy was performed using Merck Silica Gel (230e400 mesh) fol-
lowing the methods described by Still.24 Thin layer
Note: when the reaction was performed with bis-alkynyl BTD 7
2 equiv of all reagents were used.
chromatography (TLC) was performed using Merck Silica Gel GF254
,
4.5. Compound 8
0.25 mm thickness. For visualization, TLC plates were either placed
under ultraviolet light, or stained with iodine vapor, or ethanolic
solution of phosphomolybdic acid. Sugar azides were prepared
according to literature procedures.17,18 Yields refer to chromato-
graphically and spectroscopically homogeneous materials with
purity of >95%, as judged by 1H NMR spectroscopy. Spectroscopic-
grade solvents (Merck) were used for fluorescence and UVevisible
(UVevis) measurements. UVevis absorption spectra were per-
formed on a Shimadzu UV-2450 spectrophotometer. Steady-state
fluorescence spectra were measured with a Shimadzu spectroflu-
orometer model RF-5301PC. Spectrum correction was performed to
enable measuring a true spectrum by eliminating instrumental
response such as wavelength characteristics of the monochromator
or detector using Rhodamine B as a standard (quantum counter).
All experiments were performed at room temperature at a con-
Yield¼89%. Purified by flash chromatography eluting with
20
hexane/ethyl acetate (40:60). [
a
]
ꢀ50 (c 1.0, AcOEt). 1H NMR
D
(CDCl3, 400 MHz)
d
: 8.85 (s, 1H), 8.54 (d, J¼7.5 Hz, 1H), 7.93 (d,
J¼8.8 Hz, 2H), 7.76 (d, J¼7.5 Hz, 1H), 7.07 (d, J¼8.8 Hz, 2H), 6.05 (d,
J¼3.6 Hz, 1H), 4.93 (dd, J¼13.9, 7.9 Hz, 1H), 4.73 (dd, J¼13.9, 6.0 Hz,
1H), 4.65 (d, J¼3.6 Hz, 1H), 4.61 (ddd, J¼7.9, 6.0, 2.7 Hz, 1H), 4.32 (d,
J¼2.7 Hz,1H), 3.89 (s, 3H), 3.73 (br s,1H),1.47 (s, 3H),1.31 (s, 3H). 13C
NMR (CDCl3, 100 MHz) d: 159.9, 153.8, 152.4, 143.4, 133.4, 130.4,
129.6, 127.3, 125.9, 125.2, 121.2, 114.1, 112.1, 105.2, 85.2, 79.2, 74.6,
55.4, 48.4, 26.8, 26.1. IR (KBr, cmꢀ1): 3464, 2992, 2926, 2841, 1614,
1512, 1479, 1249, 1007, 821, 750, 514. HRMS (ESI) calcd for
C23H23N5O5SþH: 482.1498, found: 482.1508.
4.6. Compound 9
centration of w10ꢀ5 M. The quantum yields of fluorescence (ffl
)
were obtained at 25 ꢂC in spectroscopic-grade solvents using the
optical dilute methoddabsorbance lower than 0.05 related to a dye
concentration of 10ꢀ6 mol/L. To the quantum yields of fluorescence
calculation the refractive indices of solvents were taking into ac-
count. Quinine sulfate (Riedel) in 0.1 N H2SO4 at an excitation
wavelength of 390 nm (ffl¼0.51) was used as quantum yield
standard.25 Stock solutions of the dyes 8e11 (10ꢀ6 M) and the metal
nitrates (10ꢀ4 M) were prepared in acetonitrile and ethanol. For all
chemosensor studies the excitation wavelength was set at 405 nm.
Yield¼94%. Purified by flash chromatography eluting with ethyl
acetate/methanol (95:05). [
a
]
D
20 ꢀ36 (c 1.0, DMSO). 1H NMR (DMSO-
d6, 300 MHz)
d
: 9.02 (s, 2H), 8.55 (s, 2H), 5.94 (d, J¼3.6 Hz, 2H), 5.73
(d, J¼4.8 Hz, 2H), 4.82 (dd, J¼14.0, 3.9 Hz, 2H), 4.70 (dd, J¼14.0,
8.4 Hz, 2H), 4.64e4.48 (m, 4H), 4.17e4.15 (m, 2H), 1.35 (s, 6H), 1.24
(s, 6H). 13C NMR (DMSO-d6, 75 MHz)
d: 151.5, 141.8, 125.3, 125.2,
122.2, 110.8, 104.6, 85.1, 79.3, 73.7, 49.3, 26.6, 26.0. IR (KBr, cmꢀ1):
3440, 3147, 2994, 2922, 2889, 1219, 1090, 1011, 809. HRMS (ESI)
calcd for C26H30N8O8SþH: 615.1986, found: 615.1985.
4.2. General procedure for the Suzuki reaction5
4.7. Compound 10
A solution of CsF (1.7 mmol, 250 mg), 4-methoxyphenylboronic
acid (1.7 mmol, 250 mg), NCPePd (1 mol %), and BTD dibromide 5
(1.7 mmol, 500 mg) in dioxane in a Schlenk tube was stirred at
130 ꢂC for 24 h. After this time the reaction mixture was cooled and
the solvent removed under reduced pressure. The crude product
was purified by flash chromatography to afford the product in 85%
Yield¼87%. Purified by flash chromatography eluting with
20
hexane/ethyl acetate (70:30). [
a
]
ꢀ47 (c 1.0, AcOEt). 1H NMR
D
(CDCl3, 400 MHz)
d
: 8.89 (s, 1H), 8.60 (d, J¼7.4 Hz, 1H), 7.94 (d,
J¼8.8 Hz, 2H), 7.78 (d, J¼7.4 Hz, 1H), 7.08 (d, J¼8.8 Hz, 2H), 5.50 (d,
J¼4.9 Hz, 1H), 4.74 (dd, J¼14.2, 4.4 Hz, 1H), 4.67 (dd, J¼7.9, 2.5 Hz,
1H), 4.63 (dd, J¼14.2, 8.2 Hz,1H), 4.39e4.34 (m, 2H), 4.27 (dd, J¼7.9,
1.9 Hz, 1H), 3.90 (s, 3H), 1.55 (s, 3H), 1.46 (s, 3H), 1.39 (s, 3H), 1.29 (s,
yield. 1H NMR (CDCl3, 300 MHz)
(d, J¼8.8 Hz, 2H), 7.52 (d, J¼7.7 Hz, 1H), 7.06 (d, J¼8.8 Hz, 2H), 3.89
(s, 3H). 13C NMR (CDCl3, 125 MHz)
: 160.1, 153.9, 153.2, 133.6, 132.3,
130.4, 129.0, 127.4, 114.2, 112.2, 55.4.
d
: 7.90 (d, J¼7.7 Hz, 1H), 7.86
3H). 13C NMR (CDCl3, 75 MHz)
d: 160.9, 155.0, 153.7, 144.1, 134.1,
d
131.5, 130.9, 128.5, 126.9, 126.2, 123.0, 115.1, 110.9, 110.1, 97.3, 72.2,
71.8, 71.4, 68.2, 56.4, 51.7, 27.1, 25.9, 25.5. IR (KBr, cmꢀ1): 2983,
2936, 1724, 1379, 1248, 1208, 1069, 998, 828, 510. HRMS (ESI) calcd
for C27H29N5O6SþH: 552.1917, found: 552.1899.
4.3. General procedure for the Sonogashira reaction
To a solution of appropriate BTD bromide (0.5 mmol) in triethyl-
amine (1.5 mL) in a Schlenk tube, PdCl2(PPh3)2 (2 mg) triphenyl-
phosphine (13 mg), copperiodide(13mg), andtrimethylsilylacetylene
(0.7 or 1.4 mmol, depending on the BTD bromide used) were se-
quentially added. The reaction mixture was stirred under argon at-
mosphere at 90 ꢂC for 4 h. After this time, the solvent was evaporated
4.8. Compound 11
Yield¼91%. Purified by flash chromatography eluting with
20
hexane/ethyl acetate (70:30). [
a
]
ꢀ94 (c 1.0, AcOEt). 1H NMR
D
(CDCl3, 400 MHz)
4.74 (dd, J¼14.1, 4.3 Hz, 2H), 4.64 (dd, J¼7.9, 2.5 Hz, 2H), 4.62 (dd,
d
: 8.88 (s, 2H), 8.64 (s, 2H), 5.55 (d, J¼4.8 Hz, 2H),

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A.V. Moro et al. / Tetrahedron 69 (2013) 201e206
9. (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. Angew. Chem., Int.
Ed. 2002, 41, 2596; (b) Tornøe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem.
2002, 67, 3057.
J¼14.1, 7.9 Hz, 2H), 4.38e4.34 (m, 4H), 4.28 (dd, J¼7.9, 1.9 Hz, 2H),
1.55 (s, 6H), 1.45 (s, 6H), 1.39 (s, 6H), 1.29 (s, 6H). 13C NMR (CDCl3,
75 MHz) d: 152.3, 142.8, 125.9, 125.3, 122.7, 109.9, 109.1, 96.2, 71.1,
10. For reviews, see: (a) Kolb, H. C.; Sharpless, K. B. Drug Discov. Today 2003, 8,
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Acknowledgements
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We are grateful to Fundac¸ ao de Amparo a Pesquisa do Estado do
Rio Grande do Sul (FAPERGS), Conselho Nacional de Desenvolvi-
Int. Ed. 2008, 47, 8350; (l) Paredes, E.; Das Subha, R. ChemBioChem 20
(m) Mamidyala, S. K.; Finn, M. G. Chem. Soc. Rev. 2010, 39, 1252.
11, 12, 125;
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mento Científico e Tecnologico (CNPq), Coordenac¸ ao de Aperfei-
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c¸ oamento de Pˇ essoal de Nível Superior (CAPES), and Instituto
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Nacional de Ciencia e Tecnologia em Catalise (INCT-Catalise) for
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Supplementary data
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Copies of NMR spectra for new compounds and additional
photophysical information. Supplementary data associated with
this article can be found in the online version, at http://dx.doi.org/
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