Hydroxythiazole-based fluorescent probes for fluoride ion detection

Article abstract of DOI:10.1002/ejoc.201200140

This work describes the synthesis of five O-silyloxy-1,3-thiazoles and their use as fast-response "turn-on" probes for fluoride ion detection in polar aprotic solvents and in aqueous cetyltrimethylammonium bromide micellar medium. The fluoride-triggered d

Full text of DOI:10.1002/ejoc.201200140

FULL PAPER
DOI: 10.1002/ejoc.201200140
Hydroxythiazole-Based Fluorescent Probes for Fluoride Ion Detection
Lorena K. Calderón-Ortiz,[a] Eric Täuscher,[a] Erick Leite Bastos,[b] Helmar Görls,[c]
Dieter Weiß,*[a] and Rainer Beckert*[a]
Keywords: Heterocycles / Fluorides / Silyl ethers / Fluorescent probes
This work describes the synthesis of five O-silyloxy-1,3-thi-
azoles and their use as fast-response “turn-on” probes for
fluoride ion detection in polar aprotic solvents and in aque-
ous cetyltrimethylammonium bromide micellar medium. The
fluoride-triggered deprotection of these silyl ethers results in
ca. 180-nm shifts in the fluorescence emission wavelengths.
All compounds are suitable for the detection of fluoride ions
with a detection limit in DMSO of 10–7 molL–1; derivatives
containing a 2-pyridyl moiety in the thiazole system are more
efficient than those with a 3- or 4-pyridyl moiety. Typical an-
ionic interferents, such as acetate or chloride, are not de-
tected by O-silyloxy-1,3-thiazoles, making these compounds
very specific for fluoride.
their instability.[6] Although the use of chemiluminescence
in the detection of F– might have some drawbacks, the study
of the firefly bioluminescence[7] allowed us to design new
fluorescent probes for this application.
Nature has chosen 4-hydroxy-1,3-thiazoles as the chemi-
cal group responsible for the dual bioluminescence of the
firefly.[8] In the enzymatic oxidation of the firefly luciferin,
the keto–enol equilibrium of the 4-hydroxythiazole sub-
structure of oxyluciferin, the bioluminescence emitter,[9] is
modulated by the interaction with luciferase and results in
both yellow-green and orange-red light emission by the fire-
flies.[8b]
Introduction
The detection of fluoride ions has attracted considerable
interest due to its importance in many industrial, chemical,
and biological processes.[1] Actually, many molecules and
different methods have been established and tested for fluo-
ride ion detection. Ion chromatography and ion-selective
electrodes are suitable for the detection of fluoride in small
samples and do not require any special preparation.[1,6,7]
However, fluoride detection can prove difficult in the pres-
ence of other ions, in a low concentration of fluoride, or in
samples with high ionic strength.[1a]
Spectrophotometric methods can monitor chemical
transformations promoted by fluoride.[1c,2] Such assays ex-
ploit the strong interaction between fluoride and Lewis ac-
ids or the “turn-on” or “turn-off” deprotection approach.[3]
Triggered chemiluminescence systems have proved to be
highly efficient for the detection of some anions. The de-
composition of silyloxyaryl-substituted 1,2-dioxetanes is
triggered by fluoride ions and results in strong chemilumi-
nescence in polar aprotic solvents.[4] This method allows the
selective and sensitive detection of the F– anion.[4a] How-
ever, the major disadvantages of this approach are the diffi-
cult and expensive synthesis of 1,2-dioxetanes,[5] as well as
A recently published fluoride ion sensing method which
employs the chemical triggering of silyl ethers of 2-(2-hy-
droxyphenyl)benzothiazoles[3] prompted us to report our 4-
hydroxythiazole-based systems. We have extensively studied
their chemistry during the last decade and, on the basis of
those studies, a series of new fluorophores was devel-
oped.[10] In this work, we describe the synthesis and the
study of the photophysical properties of five O-silylated-
1,3-thiazoles, which have been designed for the sensitive and
selective “turn-on” fluorescence detection of fluoride ions
in organic aprotic solvents, as well as in aqueous micellar
media.
[a] Institute of Organic and Macromolecular Chemistry,
Friedrich Schiller University Jena,
Results and Discussion
Humboldtst. 10, 07743 Jena, Germany
Fax: +49-03641-948212
E-mail: c5diwe@uni-jena.de
Synthesis and Photophysical Properties of O-Silylthiazoles
c6bera@uni-jena.de
[b] Departamento de Química Fundamental, Instituto de Química,
Universidade de São Paulo,
Thiazoles 1a–d were obtained by condensation of N-het-
eroaromatic nitriles with thiolactic acid, whereas 1e was
prepared by the Hantzsch cyclization reaction between α-
bromophenylacetic acid and pyridine-2-carboxylic acid
thioamide.[10f,10g] Modification of the hydroxy group was
carried out with alkyl silyl chlorides 2 in the presence of
05508-000 São Paulo, SP São Paulo, Brazil
[c] Institute of Inorganic and Analytical Chemistry,
Friedrich Schiller University Jena,
Humboldtst. 8, 07743 Jena, Germany
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201200140.
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D. Weiß, R. Beckert et al.
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imidazole as a catalyst,[11] yielding O-silylthiazoles of type
3 in up to 97% yield (Scheme 1).
Scheme 1. Synthesis of O-silylthiazoles 3 starting from hydroxythi-
azoles 1 and alkyl silyl chlorides 2. DMB = 2,3-dimethylbutan-2-
yl.
Figure 2. Absorption (Ϫ) and fluorescence (···) spectra of O-silyl-
thiazoles 3 in DMSO.
X-ray crystal structure analysis of derivative 3c shows
that, due to steric interactions, the silyl group is twisted
around the C1–O1 axis by 127.1°. The pyridyl moiety is
twisted around the C3–C5 axis spanning an angle of about
123.0° with the thiazole ring (Figure 1).
the fluorescence efficiency, as well as on the absorption and
fluorescence maxima. The R3 substituent has no effect on
the photophysical properties of the compounds studied.
The presence of a 3-pyridyl group in the R1 position of
compound 3c results in a hypsochromic shift in the absorp-
tion and fluorescence bands as well as in a significant de-
crease in the fluorescence intensity (ΦFl = 0.37). In com-
parison to 3a, this can probably be explained by the re-
duction of the electronic density at the 2-position of the
thiazole ring. Conversely, the presence of a 4-pyridyl group
results in a bathochromic shift in the absorption and fluo-
rescence bands of compound 3d when compared to 3a,
possibly due to the increase in electron density. However,
the ΦFl determined for 3d is still smaller than that for 3a
(0.66 and 0.89, respectively).
Figure 1. ORTEP plot (50% probability ellipsoids) of the solid-
state molecular structure (X-ray crystallographic analysis) of deriv-
ative 3c, selected bond lengths [pm]: C1–N1 137.05(18); N1–C3
131.22(18); C3–S1 172.62(15); S1–C2 172.52(15); C2–C1 136.6(2);
C1–O1 135.12(16); O1–Si1 168.12(11).
The molecular orbitals involved in the electronic exci-
tation of compounds 1c, 3c, and 4c in DMSO are depicted
in Scheme 2. The geometry of 3c was optimized at the
B3LYP/6-31+G(d,p) level and is in good agreement with
the crystallographic data (geometric parameters are given
in Supporting Information).
All derivatives are soluble in common polar aprotic sol-
vents such as THF, DMSO, ACN, and DCM but not in
water. They also show absorption maxima in the UVA re-
gion and are highly fluorescent in the violet-blue region of
the visible spectrum (Supporting Information, Table S1).
The absorption and fluorescence spectra of compounds 3a,
3b, and 3d in DMSO as the solvent are very similar [λabs
=
344 nm, λFl = 418 nm, Stokes shift (Δλ = 5146 cm–1)]. The
absorption/emission of compound 3c are blueshifted (λabs
= 334 nm, λFl = 413 nm, Δλ = 5727 cm–1), whereas those
of 3e are redshifted (λabs = 371 nm, λFl = 447 nm, Δλ =
4583 cm–1) in relation to those of 3a. Figure 2 depicts the
absorption and fluorescence spectra of compounds 3a–e in
DMSO.
Structural variation in O-silyloxythiazoles 3 is clearly re-
flected in their fluorescence quantum yields (ΦFl). Com-
pounds 3a, 3b, and 3e containing a 2-pyridyl moiety in the
R1 position show the highest quantum yields: ΦFl = 0.89,
0.88, and 0.78, respectively. Furthermore, comparing deriv-
atives 3a and 3e, the replacement of the methyl group by a
Scheme 2. Molecular orbitals, excitation maxima, and oscillator
strength (f) of 1c, 3c, and 4c estimated at the TD-B3LYP/6-
phenyl group in the R2 position has a rather small effect on 31+G(d,p)//B3LYP/6-31+G(d,p) level.
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Hydroxythiazole-Based Fluorescent Probes for Fluoride Ion Detection
Time-dependent DFT calculations [SMD/TD-B3LYP/6- ing fluorescence emission by exciting the solutions at
31+G(d,p)//B3LYP/6-31+G(d,p)] indicate that the exci- 400 nm. In all cases, the presence of an isosbestic point con-
tation of all compounds in DMSO as the solvent shows π– firms the presence of only two species in the fluoride-trig-
π* (HOMO–LUMO) character. The most relevant infor- gered desilylation of 3 (Figure 3).
mation provided by theoretical calculation is as follows:
The absorption and fluorescence maxima, the theoretical
(1) The silyl group is not involved in the electronic transi- pKa value for the enol–enolate equilibrium, and the pKaH
tion; therefore, it is not expected that the R3 substituent for the conjugated acid of pyridine for all compounds in-
influences the electronic properties of compounds 3. volved in the fluoride-triggered desilylation of derivatives
(2) Compounds 1c and 3c show a very similar excitation 3 are shown in the Scheme 3 and given in Table 1. Data
profile as well as HOMO and LUMO electron densities, corresponding to 3 and 4 were acquired by the addition of
indicating that the protonation of red fluorescent com- TBAF to the former in DMSO. Compounds 1 were ana-
pound 4c giving 4-hydroxy-1,3-thiazole 1c would increase lyzed from solutions of the purified samples also in DMSO;
the blue fluorescence emission. (3) The occurrence of in- the spectra of 5 were registered upon addition of aqueous
ternal charge transfer from the 1,3-thiazole to the pyridine HCl to the solutions of 1.
moiety is plausible, but it should be related to a high solva-
tochromic response of the probes due to the significant
change in dipole moment upon electronic excitation;[12]
such an effect is subtle for compounds 3 in THF, DCM,
ACN, and DMSO (Supporting Information, Table S1).
Detection of Fluoride Ions
The addition of tetra-n-butylammonium fluoride
(TBAF) to a solution of compounds 3 in DMSO triggers
the cleavage of the Si–O bond, resulting in the formation of
red fluorescent enolates 4. The large emission shift upon
Scheme 3. Compounds involved in the fluoride-triggered desil-
ylation of derivatives.
desilylation of 3 (ca. 180 nm) and the high fluorescence
quantum yields of the probes are two important advantages
of the use of O-silylated-4-hydroxythiazoles in the sensitive
The protonation of the pyridine moiety of compounds
detection of fluoride. The consumption of 3 and the forma- 1 has no effect on absorption and fluorescence data when
tion of 4 were monitored simultaneously by the correspond- comparing compounds 1 and 5. On the other hand, the
Figure 3. Fluoride-triggered decomposition of derivatives 3 in DMSO and formation of enolate 4 monitored simultaneously by fluores-
cence. Spectra were acquired by excitation at 400 nm and submitted to smoothing by using the Savitzky–Golay filter with 40 points in
the moving window.
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D. Weiß, R. Beckert et al.
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Table 1. Absorption and fluorescence maxima (in nm) of all compounds involved in the fluoride-triggered decomposition of O-silylthi-
azoles 3 in DMSO.
3
λabs
4
λabs
1
λabs
5
λabs
[a]
[a]
λFl
λFl
pKa
λFl
pKaH
λFl
a
b
c
d
e
344
418
481
602
9.7
352
442
3.2
350
445
9.2[b]
9.9
334
344
371
416
419
447
473
492
516
591
602
621
343
353
382
438
447
474
4.0
5.3
3.0
345
355
382
438
446
474
9.8
8.0
[a] The pKa and pKaH values were estimated theoretically[13] and are comparable to the experimental values determined for oxyluciferin
(7.4Ͻ pKa Ͻ 8.6)[9] and pyridine (pKaH = 5.2, pKaH
= 3.5).[14] [b] Experimental value (Supporting Information, Figure S1).
DMSO
protonation of enolates 4, which has a major effect on the F–, was added to the solution of 3a in dry DMSO. Only F–
absorption and fluorescence maxima, has a pKa between induced a bathochromic shift in the spectra, which indicates
8.0 and 9.9; however, most O-silylated fluorescent probes the formation of 4a. The other anions tested are much less
are not appropriate for analysis in alkaline medium.
effective in triggering the desilylation of 3a, indicating high
All compounds of type 3 are suitable for the detection of selectivity towards the fluoride ion (Figure 5).
fluoride ions with a detection limit of 10–7 molL–1 (Fig-
ure 4). The efficiency of fluoride detection shows the follow-
ing order: 3a≈ 3bϾ 3cϾ 3eϾ 3d, that is, derivatives con-
taining the 2-pyridyl moiety in the thiazole system (i.e., 3a
and 3b) are more efficient than those with a 3- or 4-pyridyl
moiety (i.e., 3c and 3d). Furthermore, the replacement of
the methyl group at the 5-position by a phenyl group re-
duces the sensibility of the probe.
Figure 5. Fluorescence intensity of compound 4a at 600 nm after
addition of 1 equiv. of selected anions to a solution of 3a in DMSO
(8.0ϫ10–4 molL–1).
The stability of O-silyl ethers 3 towards basic and acidic
conditions was also investigated. As expected, the Si–O
bond in compound 3a was cleaved in the presence of OH–
anions at pHϾ 8, as indicated by the increase in the red
fluorescence (formation of enolate 4a, Figure 6).
Figure 4. Dependence of F– anion concentration and the fluores-
cence intensity of compounds 4. Dotted lines correspond to linear
regressions crossing the intercept; adj-R2 are as follows, 4a: 0.973,
4b: 0.997, 4c: 0.997, 4d: 0.996 and 4e: 0.966. Excitation at 400 nm;
[3a]
=
7.8ϫ10–4 molL–1, [3b]
=
6.1ϫ10–4 molL–1, [3c]
=
=
6.6ϫ10–4 molL–1,
[3d]
=
3.8ϫ10–4 molL–1,
[3e]
6.3ϫ10–4 molL–1, [TBAF] from 1ϫ10–3 to 1ϫ10–8 molL–1.
Medium and Anion Effects
The presence of ionic interference, such as hydroxide,
phosphates, acetate, or cyanide, still represents a challenge
in the selective detection of fluoride.[1a] Thus, the selectivity
of the desilylation of O-silylthiazoles towards fluoride was
investigated. One equivalent of ammonium quaternary salts
Figure 6. Effect of the addition of 0.1 molL–1 solutions of HCl and
of common anions, such as Cl–, Br–, OAc–, I–, CN–, and NaOH to the fluorescence.
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Hydroxythiazole-Based Fluorescent Probes for Fluoride Ion Detection
Additionally, the cleavage of the Si–O bond under acidic
conditions was detected by NMR spectroscopy (Figure 7).
Compound 5 is most likely formed here, which is featured
by the coexistence of protonated pyridine and the enol OH
group. This species was additionally characterized by its
emission at 474 nm. To test this hypothesis, HCl was added
to compounds 4a–e, which were generated by the desil-
ylation of the corresponding O-silyl derivatives 3. Both ab-
sorption and fluorescence maxima are blueshifted upon the
addition of acid, indicating the protonation of 4 (Support-
ing Information, Figure S2). Considering the basicity of
pyridine (pKaH = 5.2, pKaHDMSO = 3.5),[14] the data allowed
us to confirm the formation of 5a.
Figure 8. Dependence of the concentration of fluoride ion and the
fluorescence of compound 4a in aqueous CTAB micellar solution.
Excitation at 400 nm; [3a]
= =
5.9ϫ10–4 molL–1, [CTAB]
2 mmolL–1, [TBAF] from 1.2ϫ10–4 to 7.8ϫ10–4 molL–1.
fluoride, the fluorescence of 4a was only observable in
CTAB. Due to its incorporation into the micelles, that is,
a less polar microenvironment, the emission maximum is
blueshifted in comparison to water (553 nm in aqueous
CTAB vs. 602 nm in DMSO). In aqueous CTAB micelles,
the fluorescence intensity saturates upon the addition of ca.
0.8 equiv. of fluoride ion (as TBAF). The measures were
taken 10 min after the injection of TBAF solutions.
Figure 7. NMR profiles of 3a in DMSO and [D6]DMSO, respec-
tively. Attribution of extra signals: δ = 2.48 ppm (DMSO), δ =
3.32 ppm (H2O), and δ = 4.18 (d, protonated DMSO).
Conclusions
4-Hydroxythiazoles are versatile, powerful fluorophores
that allow further functionalization. Compared to most sys-
tems, the OH group is not bound to a phenyl moiety but
is located directly on the heteroaromatic ring system. The
corresponding silyl ethers are fluorescent (ΦFL Ͼ 0.4) and
its preparation is very convenient. The desilylation of these
highly efficient fluorophores by fluoride can be monitored
by a change of ca. 180 nm in the fluorescence maxima from
blue to the red in polar aprotic solvents or in aqueous
CTAB micellar medium. The detection limit was found to
be as low as 10–7 molL–1, and the simultaneous monitoring
of the consumption of O-silyl ether and formation of enol-
ate anions represent an advantage over other methods. O-
Silyloxy-1,3-thiazoles of type 3 can, therefore, be regarded
as inexpensive, selective, and sensitive probes for the detec-
tion of fluoride ions.
Determination of Fluoride in Aqueous Media in the
Presence of Surfactants
Solvation of fluoride ions by hydrogen-bond donor
(HBD) solvents plays a major role in its nucleophilicity, that
is, HBD solvents affect sensing methods based on the chem-
ical reactivity of this ion.[15] Compounds 3 are slightly solu-
ble in water, and the addition of fluoride to a solution of 3
in binary mixtures of DMSO/water as the solvent (up to
10% v/v of water) decreases the fluorescence intensity of 4,
which is blueshifted when compared to pure DMSO (Sup-
porting Information, Figure S3). Nevertheless, the detec-
tion of fluoride ions in water is possible in the presence of
selected surfactants. Therefore, we investigated the desil-
ylation of the most efficient derivative 3a, by the addition
of TBAF in aqueous medium containing the surfactants
cetyltrimethylammonium bromide (CTAB), Triton X-100,
and sodium dodecyl sulfate (SDS) at twice their critical mi-
cellar concentrations (Figure 8).
Experimental Section
Chemicals and Equipment: All reagents were purchased from com-
mercial sources and were used as received. The solvents were dried
according to common practice and distilled prior to use. Melting
points were measured by using a Büchi B-545 apparatus; NMR
spectra (CDCl3 or [D6]DMSO as solvents) were acquired with a
Bruker Advance AC-250 spectrometer; mass spectrometry was car-
The absorption and fluorescence maxima of 3a in all
three surfactants are very similar to that observed in pure
water, that is, 340/423 nm in SDS, 343/417 nm in Triton X-
100, and 342/420 nm in CTAB for absorption and fluores-
cence, respectively. On the other hand, in the presence of ried out with a VG Trio-2000 quadrupole mass spectrometer; ele-
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mental analysis (CHNOS) was performed by using Vario EL III
equipment. UV/Vis and fluorescence spectra were registered with
a Thermo/UNICAM UV 500 spectrophotometer and a JASCO
FP-6500 spectrofluorimeter, respectively.
GOOF = 1.007, largest difference peak and hole: 0.287/
–0.251eÅ–3.
4-[(tert-Butyldimethylsilyl)oxy]-5-methyl-2-(pyridin-4-yl)thiazole
(3d): Yield: 594 mg (62 %), yellow needles: 83–85 °C. 1H NMR
(250 MHz, [D6]DMSO): δ = 8.64 (dd, J = 1.65, 4.5 Hz, 2 H Py-H);
7.70 (dd, J = 1.65, 4.5 Hz, 2 H, Py-H); 2.25 (s, 3 H, methyl-H);
0.95 (s, 9 H, methyl-H); 0.27 (s, 6 H, methyl-H) ppm. 13C NMR
(62.5 MHz, [D6]DMSO): δ = 157.54, 155.55, 151.14, 140.00,
119.07, 111.13, 31.12, 26.06, 18.25, 9.81, –3.89 ppm. MS (EI): m/z
(%) = 306 (26) [M]+, 249 (100). C15H22N2OSSi (306.50): calcd. C
58.78, H 7.23, N 9.14, S 10.46; found C 58.50, H 7.11, N 9.20, S
10.48.
4-Hydroxythiazoles: Compounds were prepared as described pre-
viously.[10f,10g] Briefly, heteroaromatic nitriles (5.0 g, 50 mmol) were
molten whilst stirring under an argon atmosphere at 100 °C for 2 h
with thiolactic acid (5.2 mL, 0.05 mol) and pyridine (1 mL,
10 mmol) to obtain compounds 1a–d. For 1e, pyridine-2-carbo-
thioamide (5.0 g, 30 mmol) was stirred with ethylbromo(phenyl)-
acetate (7.3 g, 30 mmol) and pyridine (1 mL, 10 mmol). After
recrystallization from EtOH (50 mL), the 4-hydroxythiazoles were
isolated in ca. 70% yields.
4-[(tert-Butyldimethylsilyl)oxy]-5-phenyl-2-(pyridin-2-yl)thiazole
(3e): Yield: 635 mg (73%), yellow needles, m.p. 93–95 °C. 1H NMR
(250 MHz, CDCl3): δ = 8.60 (d, J = 4 Hz, 1 H); 8.07 (d, J = 8.0 Hz,
1 H); 7,84–7.74 (m, 3 H), 7,41–7.35 (m, 2 H), 7,29–7.25 (m, 2 H),
1.05 (s, 9 H), 0.46 (s, 6 H) ppm. 13C NMR (62.5 MHz, CDCl3): δ
= 159.8, 156.3, 151.4, 149.4, 136.9, 132.9, 128.6, 126.8, 126.4, 124.1,
118.9, 115.6, 25.9, 18.2, –3.9 ppm. MS (EI): m/z (%) = 368 (13)
[M]+, 311 (100), 283 (9), 179 (34), 135 (40), 121 (14). C20H24N2OSSi
(368.57): calcd. C 65.17, H 6.56, N 7.60, S 8.70; found C 64.97, H
6.67, N 7.59, S 8.27.
O-Silyl Derivatives: The appropriate 4-hydroxythiazole (0.60 g,
3 mmol) and imidazole (0.43 g, 6 mmol) were dissolved in dry
CH2Cl2 (20 mL) under an atmosphere of argon at room tempera-
ture; then, tert-butylchlorodimethylsilane (0.39 g, 3 mmol) or
chloro(2,3-dimethylbutan-2-yl)dimethylsilane (0.73 g, 4 mmol) was
added. After 3 h of stirring, the solution was filtered off and con-
centrated. After recrystallization from MeCN, O-silyl derivatives 3
were isolated as needles.
4-[(tert-Butyldimethylsilyl)oxy]-5-methyl-2-(pyridin-2-yl)thiazole
(3a): Yield: 919 mg (96%), colorless needles, m.p. 61–63 °C. 1H
NMR (250 MHz, CDCl3): δ = 8.53 (d, J = 4.7 Hz, 1 H, Py-H),
8.01 (d, J = 7.9 Hz, 1 H, Py-H), 7.72 (td, J = 1.63, 7.73, 7.80 Hz,
1 H, Py-H), 7.26–7.20 (m, 1 H, Py-H), 2.30 (s, 3 H, methyl-H),
1.02 (s, 9 H, methyl-H), 0.32 (s, 6 H, methyl-H) ppm. 13C NMR
(62.5 MHz, CDCl3): δ = 158.88, 157.27, 151.66, 149.19, 136.76,
123.57, 118.73, 111.00, 25.81, 18.14, 9.77, –4.25 ppm. MS: m/z (%)
= 306 (18) [M]+, 249 (100). C15H22N2OSSi (306.50): calcd. C 58.78,
H 7.23, N 9.14, S 10.46; found C 58.77, H 7.10, N 9.13, S 10. 31.
UV/Vis and Fluorescence Measurements: Stock solutions of 3
(10–4 molL–1) and TBAF (10 mmolL–1) were prepared in spectro-
scopic grade DMSO, MeCN, THF, CH2Cl2, and aqueous surfac-
tant solution. The reaction was initiated by adding the adequate
volume of TBAF to a solution of 3 in a quartz cell stopped with a
septum under magnetic stirring. Fluorescence spectra were re-
corded from 400 to 750 nm.
Computational Details: Gaussian09 was used for all calculations.[16]
All structures were optimized in the gas phase at the B3LYP/6-
31+G(d,p) level.[17] Stationary points were characterized as minima
by vibrational analysis. Vertical excitation energies were estimated
in DMSO by using the TD-DFT method at the B3LYP/6-
31+G(d,p)//B3LYP/6-31+G(d,p) level. To model the solvent effects
(DMSO), the SMD parameterization of the IEFPCM was em-
ployed.
4-(2,3-Dimethylbutan-2-yl)dimethylsilyloxy-5-methyl-2-(pyridin-2-
yl)thiazole (3b): Yield: 960 mg (92%), colorless needles, m.p. 66–
1
68 °C. H NMR (250 MHz, CDCl3): δ = 8.53 (d, J = 4.9 Hz, 1 H
Py-H), 8.00 (d, J = 7.9 Hz, 1 H Py-H), 7.76–7.69 (m, 1 H Py-H),
7.26–7.19 (m, 1 H, Py-H), 2.16 (s, 3 H, methyl-H), 1.80–1.69 (m, 1
H, tert-H), 0.99–0.95 (m, 12 H, methyl-H), 0.36 (s, 6 H, methyl-H)
ppm. 13C NMR (62.5 MHz, CDCl3): δ = 206.85, 158.79, 157.23,
151.68, 149.17, 136.76, 123.54, 118.73, 111.00, 34.17, 30.88, 25.11,
20.25, 18.57, 9.8, –2.27 ppm. MS (EI): m/z (%) = 334 (15) [M]+,
249 (100). C17H26N2OSSi (334.15): calcd. C 61.03, H 7.83, N 8.37,
S 9.58; found C 61.00, H 7.71, N 8.45, S 9.32.
Crystal Structure Determination: The intensity data for the com-
pounds were collected with a Nonius KappaCCD diffractometer
by using graphite-monochromated Mo-Kα radiation. Data were
corrected for Lorentz and polarization effects but not for absorp-
tion effects.[18,19] The structures were solved by direct methods
(SHELXS[20]) and refined by full-matrix least-squares techniques
4-[(tert-Butyldimethylsilyl)oxy]-5-methyl-2-(pyridin-3-yl)thiazole
(3c): Yield: 938 mg (98 %), colorless needles, m.p. 70–72 °C. 1H
NMR (250 MHz, CDCl3): δ = 9.06 (s, 1 H, Py-H), 8.56 (s, 1 H,
Py-H), 8.08 (d, J = 8.0 Hz, 1 H, Py-H), 7.34–7.26 (m, 1 H, Py-H),
2.28 (s, 3 H, methyl-H), 1.02 (s, 9 H, methyl-H), 0.32 (s, 6 H,
methyl-H) ppm. 13C NMR (62.5 MHz, CDCl3): δ = 157.48, 155.04,
149.75, 146.56, 132.27, 130.07, 123.57, 108.66, 25.79, 25.66, 18.12,
9.56, –3.80 ppm. MS (EI): m/z (%) = 306 (12) [M]+, 249 (100).
C15H22N2OSSi (306.50): calcd. C 58.78, H 7.23, N 9.14, S 10.46;
found C 58.65, H 6.99, N 9.10, S 10.26. X-ray Crystal Data: Empir-
ical formula: C15H22N2OSSi, M = 306.50 gmol–1, colorless prism,
size 0.05 ϫ0.05 ϫ0.04 mm3, monoclinic, space group P21/c, a =
10.5185(2) Å, b = 9.4990(2) Å, c = 16.7346(3) Å, β = 98.017(1)°, V
= 1655.70(6) Å3, T = –140 °C, Z = 4, ρcalcd. = 1.230 gcm–3, μ(Mo-
Kα) = 2.66 cm–1, F(000) = 656, 9790 reflections in h(–12/13), k(–10/
12), l(–21/21), measured in the range 2.90° Յ ΘՅ 27.44°, complete-
ness Θmax = 99.5%, 3758 independent reflections, Rint = 0.0246,
3395 reflections with Fo Ͼ 4σ(Fo), 269 parameters, 0 restraints,
R1-obs = 0.0348, wR2-obs = 0.0894, R1-all = 0.0403, wR2-all = 0.0947,
2
against Fo (SHELXL-97[20]). All hydrogen atoms were located by
difference Fourier synthesis and refined isotropically. All non-hy-
drogen atoms were refined anisotropically.[20] XP (Siemens Analyti-
cal X-ray Instruments, Inc.) was used for structure representations.
CCDC-865129 (for 3c) contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Supporting Information (see footnote on the first page of this arti-
cle): Absorption and fluorescence maxima and Stokes shift of 3 in
polar aprotic solvents, deprotonation of 1a as a function of the
medium pH, absorption and fluorescence spectra of 4 and 4 + HCl,
effect of water concentration of the fluorescence spectra of 4c after
deprotection of 3c with TBAF in DMSO, XYZ coordinates, copies
1
of the H NMR and 13C NMR spectra.
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© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2012, 2535–2541

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Acknowledgments
This work was supported by the Deutscher Akademischer Aus-
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Received: February 7, 2012
Published Online: March 14, 2012
Eur. J. Org. Chem. 2012, 2535–2541
© 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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