Synthesis and evaluation of thiosemicarbazones functionalized with furyl moieties as new chemosensors for anion recognition

Article abstract of DOI:10.1039/c2ob26200b

A family of heterocyclic thiosemicarbazone dyes (3a-f and 4) containing furyl groups was synthesized in good yields, characterized and their response in acetonitrile in the presence of selected anions was studied. Acetonitrile solutions of 3a-f and 4 show

Full text of DOI:10.1039/c2ob26200b

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PAPER
Synthesis and evaluation of thiosemicarbazones functionalized with furyl
moieties as new chemosensors for anion recognition†
Luis E. Santos-Figueroa,a,b María E. Moragues,a,b M. Manuela M. Raposo,*c Rosa M. F. Batista,c
Susana P. G. Costa,c R. Cristina M. Ferreira,c Félix Sancenón,a,b Ramón Martínez-Máñez,*a,b
José Vicente Ros-Lisa,b and Juan Sotoa
Received 12th March 2012, Accepted 19th July 2012
DOI: 10.1039/c2ob26200b
A family of heterocyclic thiosemicarbazone dyes (3a–f and 4) containing furyl groups was synthesized in
good yields, characterized and their response in acetonitrile in the presence of selected anions was
studied. Acetonitrile solutions of 3a–f and 4 showed absorption bands in the 335–396 nm range which
are modulated by the electron donor or acceptor strength of the heterocyclic systems appended to the
thiosemicarbazone moiety. Fluoride, chloride, bromide, iodide, dihydrogen phosphate, hydrogen sulphate,
nitrate, acetate and cyanide anions were used in recognition studies. From these anions, only sensing
features were seen for fluoride, cyanide, acetate and dihydrogen phosphate. Two clearly different chromo-
fluorogenic behaviours were observed: (i) a small shift of the absorption band due to the coordination of
the anions with the thiourea protons and (ii) the appearance of a new red shifted band due to
deprotonation. For the latter effect, a change in the colour of solution from pale yellow to purple was
observed. Fluorescence studies were also in agreement with the different effects observed in the UV/Vis
titrations. In this case, hydrogen bonding interactions were visible through the enhancement of the
emission band, whereas deprotonation induced the appearance of a new red-shifted emission. Logarithms
of stability constants for the two processes (complex formation + deprotonation) for receptors 3a–f in the
presence of fluoride and acetate anions were determined from spectrophotometric titrations using the
HypSpec V1.1.18 program. Semi-empirical calculations to evaluate the hydrogen-donating ability of the
receptors and a prospective electrochemical characterization of compound 3b in the presence of fluoride
were also performed.
Introduction
instrumentation. Apart from the development of fluorescent
probes, chromogenic recognition has drawn attention because it
offers the possibility of straightforward semiquantitative “naked-
eye” detection.2 Moreover, the colorimetric probes showing a
simple displacement of the absorption band allow one to
develop ratiometric methods, thus avoiding the use of an internal
reference. Optical detection for metal cations was developed
more than two decades ago,3 yet anionic chromogenic receptors
have only recently been investigated.4 The latter focus on anions
are mainly due to the more challenging chemistry of host–anion
interactions, the lower stability constants observed with anionic
species when compared with metal cations, the complex and
varied shapes found for anions, their possible dependence on pH
and the strong competition of water usually found for receptor–
anion complexes based on hydrogen-bonding interactions.5
Despite these setbacks, the supramolecular chemistry of
anions has advanced a great deal in the last few years mainly
due to the progress made in the knowledge of how the formation
of host–anion complexes operates. Based on these advances, a
number of receptors for anion binding have been developed,
The development of new molecular systems for the detection of
anions, cations or neutral molecules has gained prime impor-
tance in recent years due to the significance of detecting target
species in biological and environmental samples. In this area,
designed receptors are able to transform, upon coordination,
host–guest interactions into a measurable signal which allows
analyte recognition and sensing through optical or electro-
chemical responses.1 In particular, optical outputs are attractive
given the possibility of using low-cost, widely available
aCentro de Reconocimiento Molecular y Desarrollo Tecnológico (IDM),
Unidad Mixta Universidad de Valencia-Universidad Politécnica de
Valencia, Departamento de Química UPV, Camino de Vera s/n, 46022
Valencia, Spain. E-mail: rmaez@qim.upv.es
bCIBER de Bioingeniería, Biomateriales y Nanomedicina
(CIBER-BBN),
cCentro de Química, Universidade do Minho, Campus de Gualtar,
4710-057 Braga, Portugal. E-mail: mfox@quimica.uminho.pt
†Electronic supplementary information (ESI) available. See DOI:
10.1039/c2ob26200b
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most of which are based on hydrogen bonding and electrostatic
interactions.6 In contrast to purely electrostatic interactions,
which are only distance-dependent, hydrogen bonds offer the
advantage of being directional which allows one to discriminate
between anions of different geometries or hydrogen-bonding
requirements.7 Among the neutral anion binding groups, thioureas
and thiourea-containing fragments have been widely used for the
formation of complexes with anions because the hydrogen-bonding
ability of these functional groups commonly results in the for-
mation of quite stable complexes, and also because they can be
easily synthesized from commercially available reagents by a
single-step procedure.8 In fact, thiourea derivatives have been the
subject of intense research given their performance in the develop-
ment of anion receptors and, for instance, thioureas (and also
ureas) have been demonstrated as good coordinating groups for
Y-shaped anions such as carboxylates.9 Moreover, the hydrogen-
bonding ability of the thiourea moiety depends on the acidity of
the thioureido NH protons and the number of binding sites. A
means of tuning this acidity is to introduce electron-donating or
electron-withdrawing substituents.10 Additionally, experimental and
theoretical studies have demonstrated that replacing the benzene
ring of a chromophore bridge with easily delocalizable five-
member heteroaromatic rings, such as thiophene, pyrrole and thia-
zole, results in enhanced intramolecular electronic delocalization.11
On the other hand, among the molecules containing thiourea
fragments, the use of thiosemicarbazones has recently gained
interest as potential receptors. Schiff base compounds containing
thiosemicarbazone groups have also grown in the biology and
chemistry areas due to ample biological activity,12 such as anti-
tumoural, fungicidal, bactericidal, or antiviral, and nonlinear
optical properties.13 Moreover, thiosemicarbazones have also
gained attention recently as anion receptors due to their easy syn-
thesis. Also, thiosemicarbazones will be easily included in aro-
matic frameworks functionalized with acceptor and donor
moieties in order to fine tune the acidity of the NH protons. In
fact, we and others have recently demonstrated that π-conjugated
heterocyclic derivatives, containing thiosemicarbazone moieties,
are suitable systems for the colorimetric and fluorimetric sensing
of anions.14 Following this previous work on the synthesis and
evaluation of thiosemicarbazones as binding groups, and by also
considering our interest in the development of new probes for
anion recognition, we report herein the synthesis and the charac-
terization of new N-phenylthiosemicarbazones. As a special
feature, these newly reported derivatives additionally contain
heteroaromatic π-conjugated systems (instead of the more com-
monly used benzene rings) because anion chemosensors contain-
ing phenylthioureas functionalized with heterocyclic moieties
are still unusual. The new reported receptors contain furan
(instead of thiophene as we have reported recently)14 as aromatic
rings. The underlying idea of the present paper was to evaluate
the effect in the binding efficiency of the thiosemicarbazone
moiety upon functionalization with furan groups.
conjugating bridges were used to evaluate the influence of the
structure modification (i.e., donating and accepting strength of
these groups, and the nature and length of the π-conjugated
bridge) on the optical properties of prepared N-phenylthiosemi-
carbazones 3a–f and 4. The new compounds containing furan
and arylfuran π-conjugated bridges were synthesized in good
yields (76–96%) through the Schiff-base condensation of hetero-
cyclic aldehydes 1a–g with 4-phenyl-3-thiosemicarbazide in
methanol at room temperature (see Scheme 1).
Aldehydes 1a–c and 1e–f are inexpensive and commercially
available, and 5-(4′-ethoxyphenyl)furan-2-carbaldehyde 1d15
and the precursor 5-(4′-formylphenyl)furan-2-carbaldehyde 1g
were easily prepared in good yields (75–91%) through Suzuki
cross-coupling reactions of 5-bromofuran-2-carbaldehyde with
4-ethoxyphenylboronic acid or 4-formylphenylboronic acid,
respectively, using the synthetic procedure previously reported
by us.11a All the compounds were completely characterized by
1H and 13C NMR, IR, MS, EA or HRMS, and the data obtained
were in full agreement with the proposed formulation (see
1
Experimental section). The H NMR spectra of this family of
thiosemicarbazones show the most characteristic signals for N–H
and CHvN protons. 1H NMR studies using deuterated N,N-
dimethylsulphoxide (DMSO) displayed resonances due to the
CHvN protons in the 7.99–8.16 ppm interval, whereas thiourea
N–H protons were found in the 9.88–10.18 and
11.84–12.23 ppm range for the N–H groups adjacent to the
monosubstituted phenyl ring and for the N–H adjacent to the
CHvN moiety, respectively. When the whole family of com-
pounds was considered, the highest variations in δ were found
for the N–H protons located in the vicinity of the CHvN moiety
adjacent to the furan ring functionalized with electron withdraw-
ing or electron donor groups (Δδ = 0.39 ppm). Additionally, the
CHvN protons were the least affected by the substituents
located in their vicinity (Δδ = 0.17 ppm), whereas the N–H
protons adjacent to the monosubstituted phenyl ring showed an
interval of Δδ = 0.30 ppm.
Spectroscopic behaviour of 3a–f and 4
Acetonitrile solutions (C = 1.2 × 10−5 mol dm−3 at 25 °C) of
thiosemicarbazone-functionalised receptors 3a–f and 4 showed
an intense absorption band (log ε ≈ 4.4) in the 335–396 nm
region (see Table 1 for spectroscopic data). Compound 3a,
containing the thiosemicarbazone moiety surrounded by a
Results and discussion
Synthesis and characterization
Different formyl precursors 1a–g containing several substituents,
such as bromo, nitro and alkoxy, linked to different π
Scheme 1 Synthesis of furyl-thiosemicarbazone receptors 3a–f and 4.
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Table 1 Spectroscopic data for compounds 3a–f and 4
Receptor
λab LH (nm)
λab L− a (nm)
Log ε (LH)
λem LH (nm)
λem L− a (nm)
Φ
Δλ ab-em LH (nm)
Δνab-em LH (cm−1
)
3a
3b
3c
3d
3e
3f
4
335
383
362
366
364
396
359
391
540
416
410
423
489
443
4.55
4.27
4.59
4.01
4.61
4.31
4.53
421
422
426
432
429
586
486
431
409
491
462
476
546
467
0.0016
0.0006
0.0226
0.0644
0.0183
0.0259
0.0363
86
39
64
66
65
190
127
6097.78
2412.98
4150.13
4174.26
4162.50
8187.68
7279.02
a Measured upon addition of 100 equiv. of the fluoride anion.
Fig. 1 Colour changes of the 3b solution (1.2 × 10−4 mol dm−3) seen
in the presence of 10 equiv. of F−, Cl−, Br−, I−, CN−, NO3−, AcO−,
−
ClO4−, HSO4− and H2PO4
.
phenyl and a furyl ring functionalized with a bromo group, pre-
sented an absorption band at 335 nm, whereas changing the
bromo substituent for a better electron acceptor moiety, such as a
nitro group (receptor 3b), induced a pronounced red shift from
335 to 383 nm. The coupling of an additional aromatic ring with
the framework of 3a or 3b (receptors 3e and 3f, respectively)
induced a significant bathochromic shift of the band (from
335 to 364 nm and from 383 to 396 nm, respectively), this being
a direct consequence of the extension of the conjugation.
Fig. 2 UV-Vis titration of receptor 3b (1.2 × 10−5 mol dm−3) with F−
anion (0–10 equiv.) in acetonitrile. Inset: Absorbance of a solution of 3b
at 383 and 540 nm versus concentration of F− anion (mol dm−3).
the red-shifted band upon addition of fluoride were dependent
on the receptor used. Acetonitrile solutions of 3b were yellow
due to the presence of a band at 383 nm. Upon addition of
increasing quantities of the fluoride anion, this band progress-
ively decreased, while a new absorption at 540 nm (Δλ =
157 nm) increased in intensity with a clear isosbestic point at
429 nm (see Fig. 2). The formation of this new visible band
induced a change in colour from pale yellow to purple (see
Fig. 1).
Fluoride and cyanide anions were able to induce UV-Vis
changes for all the receptors tested, whereas acetate and hydro-
gen phosphate displayed a poorer response with all the receptors
(see Fig. 3).
The selectivity of receptors 3a–b and 4 for the most basic
anions (F−, CN−, AcO− and H2SO4−) was demonstrated by
further UV-Vis experiments. Fig. 4 shows that addition of 10
equiv. of fluoride anion to acetonitrile solutions of receptor 3b
induced the appearance of an absorbance band at 540 nm. The
same red-shifted band with identical absorbance was obtained
upon addition of a mixture of anions (10 equiv. of fluoride,
chloride, bromide, iodide, perchlorate, hydrogen sulfate and
nitrate). Similar chromogenic behaviors were observed for CN−
and AcO− in mixtures with other anions (i.e. chloride, bromide,
iodide, perchlorate, hydrogen sulfate and nitrate).
UV-Vis studies involving anions
The UV-Vis behaviour of receptors 3a–f and 4 in acetonitrile
solutions (C = 1.2 × 10−5 mol dm−3) was studied at 25 °C in the
presence of selected anions of different sizes and shapes such as
fluoride, chloride, bromide, iodide, cyanide, nitrate, acetate, per-
chlorate, hydrogen sulphate and dihydrogen phosphate. For all
the receptors, addition of increasing quantities (up to 10 equiv.)
of chloride, bromide, iodide, nitrate, perchlorate and hydrogen
sulphate induced negligible changes in the UV-Vis bands, which
clearly indicates that no coordination occurs. Much more rel-
evant results were observed in the presence of those anions
showing a basic character in acetonitrile, such as fluoride,
cyanide, acetate, and dihydrogen phosphate (see Fig. 1). The
changes in colour observed upon addition of basic anions were
almost immediate (see ESI† for the kinetic profile of changes in
the 390 nm band of 3b in the presence of the fluoride anion).
In most cases, UV-Vis titration experiments with receptors
3a–f and 4 and fluoride showed similar behaviour; i.e., intensity
decreased and there was a slight hypsochromic shift of the
absorption band, together with simultaneous growth of a new
red-shifted band. However, it was clearly apparent from the titra-
tion profiles that both the position of the new band and the rela-
tive intensity of the absorption band of the receptor in relation to
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complexes between these groups and to the highly basic F−
anion that is eventually able to originate the deprotonation of the
binding site.17 In fact, we believe that this dual complex + depro-
tonation process is active in all of our receptors in the presence
of fluoride: a first step consisting in the formation of a hydrogen-
bonding complex and a second step in which the receptor is
deprotonated by the anion. Usually the formation of hydrogen-
bonding complexes, via receptor-interactions, is reflected in rela-
tively minor variations in the absorption band of the receptor,
whereas the deprotonation processes are revealed with the clear
appearance of a new absorption band at longer wavelengths.18
From a more physical viewpoint, the negative charge generated
upon deprotonation induces an increase in the intensity of the
electrical dipole that results in a substantial red shift of the
absorption band. In most cases, the observation of complexation
or/and deprotonation depends on a delicate balance between the
acidity of the N–H protons of the receptor and the basicity of the
anion. In our case, a close look at the results indicated that the
final response of receptors 3a–f and 4 to the tested basic anions
strongly depends on the chemical nature of the functional groups
attached to the thiosemicarbazone framework, which modulated
the acidity of the N–H protons; i.e. for a certain anion (fluoride)
at a given concentration, the development of the band due to
deprotonation grew more or less in intensity depending on the
receptors used.
Fig. 3 UV-Vis titration of receptors 3b (1.2 × 10−5 mol dm−3) with
AcO− anion (0–10 equiv.) in acetonitrile. Inset: Absorbance of aceto-
nitrile solutions of receptor 3b at 383 and 540 nm versus concentration
of AcO− anion (mol dm−3).
When comparing the behaviour of similar compounds 3a–f, it
was apparent that the presence of electron-withdrawing moieties,
such as a nitro group in 3b and 3f, induced an increase in the
acidity of the N–H protons of the thiosemicarbazone, thus
favouring the interaction with the fluoride and cyanide anions
and deprotonation, whereas the presence of electron-donor
groups, such as bromo (3a) and ethoxy (3d), respectively
induced a certain decrease in acidity and the red-shifted band
due to deprotonation developed to a lesser extent.
Fig. 4 Absorbance at 540 nm of receptor 3b (1.0 × 10−5 mol dm−3
)
Stability constants
alone and upon addition of 10 equiv. of F− and 10 equiv. of F−, Cl−,
Br−, ClO4−, HSO4−, I− and NO3− anions.
As stated above in the interaction of basic anions with semithio-
carbazone-containing receptors 3a–f and 4, two different beha-
viours could be expected; i.e., (i) hydrogen-bonding interactions
and (ii) deprotonation (see eqn (1) and (2)).
Once the selectivity of this family of receptors was deter-
mined, the limits of detection (LOD) were estimated. In all cases
LOD values of ca. 10 μM were determined for fluoride and
cyanide anions.
ꢀ
LH þ Aꢀ LH ꢁ ꢁ ꢁ A
ð1Þ
ð2Þ
!
LH ꢁ ꢁ ꢁ Aꢀ þ Aꢀ L þ A2H
ꢀ
ꢀ
!
Moreover the interaction of 3a–f and 4 with basic anions in
water and acetonitrile–water mixtures (1 : 1, 5 : 1 and 10 : 1 v/v)
was also tested. Unfortunately in all cases neither changes in
colour nor in fluorescence were observed. This was most likely
due to the reduced basicity of the anions in aqueous environ-
ments due to solvation and the poor acidity of the receptors
when compared with other reported ligands (vide infra).
On the whole, the changes observed in acetonitrile are in
agreement with the expectation that the interaction between an
electron-rich anion and a donor group in a push–pull system will
induce a bathochromic shift. In fact, similar shifts in the presence
of fluoride have also been reported to occur using other amide-,
urea-, thiourea-, or pyrrole-containing hosts.16 This interaction is
attributed to the formation of strong hydrogen-bonding
In order to complete the characterization of the interaction of
receptors 3a–f and 4 with anions, the strength of both processes
(coordination and deprotonation) was studied via the evaluation
of the corresponding stability constants, which were deter-
mined by the UV-Vis spectroscopic titrations between receptors
3a–f and 4 and fluoride and acetate anions using the HypSpec
software V1.1.18. The data set was adjusted to the two consecu-
tive equilibriums in eqn (1) and (2); the results are shown in
Table 2.
In all cases, the formation of anion–ligand 2 : 1 complexes
shown in eqn (2) was confirmed for the method of continuous
variation (Job’s plots). As an example Fig. 5 shows the studies
for the interaction of 3b with fluoride. It is noticeable that
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Table 2 Logarithms of the stability constants measured for the
interaction of receptors 3a–f with fluoride and acetate
with logarithms of the stability constants for the formation of the
complex and for the deprotonation of 7.38 and 6.37 respect-
ively.19 Another urea-based receptor (1-nitrobenzo[1,2,5]oxadia-
zol-4-yl)-3-(4-nitrophenyl)urea showed logarithm values higher
than 6 for the formation of the hydrogen-bonding complexes and
4.2 for the deprotonation step.20 Finally, the thiourea receptor
1-(2-methyl-1,3-dioxo-2,3-dihydro-1H-isoindol-5-yl)-3-phenyl-
thiourea also underwent a first coordination step and a second
proton transfer process with the basic anions, with a logarithm of
stability constants 5.7 and 5.5 for fluoride, and 6.02 and 3.23 for
acetate.21
F−
AcO−
LH + A−
⇄
LH⋯A− + A−
⇄ L− + A2H−
LH + A−
LH⋯A−
⇄
LH⋯A− + A−
⇄ L− + A2H−
LH⋯A−
3a
3b
3c
3d
3e
3f
3.46(6)
4.56(2)
4.20(5)
4.23(4)
4.37(1)
4.47(7)
2.48(7)
4.24(4)
3.51(8)
3.81(8)
3.57(7)
4.47(1)
3.40(6)
3.91(1)
3.60(1)
—
3.56(8)
4.56(8)
0.31(8)
1.53(4)
0.13(4)
—
0.31(2)
1.64(1)
a
a
a No reliable results were obtained.
Fluorogenic studies involving anions
It is widely known that fluorescence, despite being a less
extended technique in some cases, is much more sensitive to
intermolecular interactions than colour changes. Therefore, fluor-
escence studies in acetonitrile solutions of the receptors upon
addition of increasing amounts of the corresponding anion were
carried out. Receptors were excited in the pseudo-isosbestic
points observed in the course of UV-Vis titrations. In all cases,
the emission consisted in a broad, unstructured band. Quantum
yields in acetonitrile (see Table 1) ranged from quite low (recep-
tor 3a, Φ = 0.0016) to medium (compound 3d, Φ = 0.0644). For
all the receptors tested (i.e., 3a–f and 4), addition of the anions
chloride, bromide, iodide, hydrogen sulphate and nitrate induced
negligible changes in the emission intensity profiles. In contrast,
the fluorescence emission in the presence of fluoride, cyanide,
acetate and dihydrogen phosphate changed significantly.
Fig. 5 Job’s plot for complexation of 3b with the fluoride anion deter-
mined by UV-Vis spectrophotometry in acetonitrile at 540 nm and
[3b] + [F−] = 1.2 × 10−4 mol dm−3
.
A different general behaviour was found depending on the
anion and the receptor used in the studies. As a general trend,
and in the presence of fluoride, all the receptors 3a–f and 4
showed enhanced fluorescence intensity upon the addition of
moderate amounts of fluoride followed by a quenching of the
emission band at higher anion concentrations and the growth of
a new band at longer wavelengths (λem in the 421–586 nm
range, see Table 1).
despite the presence of two potential binding sites in 4, this
receptor showed the same response as 3a–f, namely the for-
mation of 2 : 1 anion–ligand stoichiometry complexes.
Table 2 shows that, as a general trend, the logarithms of the
stability constants measured for both equilibriums with fluoride
were higher than those obtained for acetate. This is in agreement
with the more basic character of fluoride in acetonitrile when
compared with acetate. The logarithms of the stability constants
for the formation of the Y-shaped hydrogen-bonding complexes
were about one order of magnitude larger than the logarithms of
the stability constants for the deprotonation for fluoride, and
about three orders of magnitude larger for acetate. It is also
apparent in Table 2 that the deprotonation logarithms of con-
stants for all the receptors were more important for fluoride than
for acetate.
The stability constants for the formation of the corresponding
hydrogen-bonding complexes remained approximately the same
for both anions. It is noteworthy that the logarithms of stability
constants determined in this study for thiosemicarbazones were
generally lower than those reported for the other urea/thiourea
receptors functionalized with benzene rings containing electron
withdrawing moieties. This is a clear consequence of the
reduced acidity of the receptors studied herein when compared
with other reported ligands. For instance, compound 1,3-bis-
(4-nitrophenyl)urea has also been reported to display the two-step
process (coordination + deprotonation) upon addition of fluoride
In order to interpret this behaviour, we made a comparison
between the changes observed in the emission and absorption
spectra. A typical example is that shown in Fig. 6, namely the
behaviour found for ligand 3e in the presence of fluoride. As
seen, for small quantities of the fluoride anion, while the inten-
sity of the absorption band at 364 nm remains unaltered, the flu-
orescence intensity at 429 nm progressively increased until 10
equiv. of fluoride had been added. Moreover, upon addition of
larger amounts of fluoride, the intensity of the emission band at
429 nm diminished, suggesting the formation of a new com-
pound that emits at longer wavelengths (λem = 476 nm). Thus,
fluorescence measurements suggest that the interaction of the
receptors with fluoride took place in two steps, as found in the
UV-Vis studies. In the first step, the anion coordinates with the
acidic NH protons of the thiourea moiety through hydrogen-
bonding interactions and led to an increase in the donor capacity
of the binding site. Upon addition of more equivalents of the
anion, deprotonation of the receptor occurred. This deprotonation
process induced the appearance of the red-shifted visible and
emission bands.
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Fig. 6 Interaction of receptor 3e (1.2 × 10−5 mol dm−3) with F− anion
(top): absorption spectra and (bottom): emission spectra of receptor in
the presence of 0, 1, 8, 10, 20 and 100 equiv. of F− anion.
The overall shape and intensity of the emission band for a
certain receptor–anion pair depends on the LH/LH⋯A−/L−
ratios. For instance, a closer look at the titration experiments
with fluoride indicated that in order to induce the appearance of
the red-shifted emission band, larger amounts of fluoride are
required for receptor 3e (functionalized with bromophenylfuryl)
than for receptor 3f (functionalized with nitrophenylfuryl),
which is in agreement with the larger acidity of 3f versus 3e.
Fig. 7 shows the emission and absorption spectra for receptor
3e in the presence of acetate. The emission intensity was enhanced
upon the addition of increasing quantities of the acetate anion.
This enhancement in the emission intensity was assigned to the
formation of the Y-shaped hydrogen-bonding complex between
the NH thiourea protons of the receptor and the acetate anion.
However in this case, no significant deprotonation occurred and
no red-shifted absorptions or emission bands were observed.
Fig. 7 Interaction of receptor 3e (1.2 × 10−5 mol dm−3) with AcO−
anion (top): absorption spectra and (bottom): emission spectra of the
receptor in the presence of 0, 1, 8, 10, 20 and 100 equiv. of AcO− anion.
In order to study the coordination/deprotonation processes in
these systems in more detail, the interaction of receptor 3b with
the fluoride anion was investigated by means of 1H NMR titration
experiments in DMSO-d6. Deuterated DMSO was selected as the
solvent due to the poor solubility of 3b in deuterated acetonitrile.
1
The H NMR spectrum of 3b showed the expected signals in
the aromatic zone due to the presence of one benzene ring and
one furan heterocycle. The monosubstituted benzene ring
showed resonances at 7.21–7.26 (1H, multiplet, Hp), 7.39 (2H,
broad triplet, Hm), 7.52–7.56 (2H, multiplet, Ho) ppm, whereas
the protons of the 2,5-disubstituted furan ring (Hd and Hc) appeared
as a broad doublet at 7.50 (Hd) and at 7.83 (Hc) ppm. Finally, the
imine proton (–CHvN) was a broad singlet at 8.08 (He) ppm, and
the N–H protons of the thiosemicarbazone group were also broad
singlets at 10.18 (Hg) and 12.23 (Hf) ppm (Scheme 2).
In a first step, we studied the shifts of the protons of receptor
3b upon addition of increasing quantities of the fluoride anion.
The most important fact was the disappearance of the Hf and Hg
protons upon addition of 1 equiv. of fluoride. Additionally, the
1H-NMR spectroscopic studies in the presence of anions
As seen previously, the UV-Vis and fluorescence data of thio-
semicarbazone receptors 3a–f and 4 in the presence of anions
displayed a varied response related with the presence of hydro-
gen-bonding interactions and the deprotonation of the receptors.
In particular, the colorimetric behaviour observed for these
receptors depends on the deprotonation tendencies of the thiose-
micarbazone units in receptors 3a–f and 4 and on the proton
affinities of the anions.
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Table 3 Stabilization energy of the deprotonation for receptors
E(L) − E(LH) (kcal mol−1
R = N-NH-C(S)-N-Pha
)
Receptor
R = N-N-C(S)-NH-Phb
3a
3b
3c
3d
3e
3f
−5.87
−5.18
−6.16
−6.35
−6.84
−10.20
−13.66
−14.56
−14.93
−14.33
−14.67
−18.86
a Deprotonation at the Hg proton (see Scheme 2). b Deprotonation at the
Hf proton (see Scheme 2).
Fig. 8 1H NMR shifts for the protons of receptor 3b in the presence of
increasing quantities of F− anion (DMSO-d6).
variation in the chemical shifts Δδ (ppm) for other protons in 3b
during the titration with fluoride is shown in Fig. 8.
As seen, protons Hc, Hd and He showed negligible changes in
their position in the NMR spectrum. In contrast, remarkable
shifts were noted for Ho, Hm and Hp, suggesting that deprotona-
tion took place in the N–H group closer to the phenyl group. It
has been reported that upon the deprotonation of the N–H group,
two effects might become active: (i) an increase in the electron
density in the phenyl ring according to a π-mechanism, which
should induce a shielding effect (an upfield shift of the C–H
signals is expected), and (ii) a polarization of the C–H bonds
induced by a through-space electrostatic mechanism, which is
expected to cause a deshielding effect. Fig. 8 shows how the Ho
protons underwent important downfield shifts, indicating strong
electrostatic effects due to the proximity of a negatively charged
thiourea nitrogen atom. Protons Hm and Hp underwent upfield
shifts as a result of the through-bond effect which, in this case,
dominated (through-space effects vanished with distance). Fab-
brizzi et al. and ourselves have observed a similar behaviour in
closely related thioureas; i.e., deprotonation apparently occurred
in the protons of the nitrogen attached to the phenyl ring.22
Scheme 2 Proposed mode for fluoride-induced deprotonation of recep-
tor 3b.
receptors. Among the compounds studied using a PM3 semi-
empirical model, we can observe that the presence of an extra
phenyl ring next to the furyl moiety (compounds 3c–3f) made
the receptors more acidic when compared with derivative 3a.
Moreover, the quantum mechanical studies indicate that deriva-
tive 3f was the most acidic one. In fact, the acidity of the studied
receptors followed this order 3f > 3c ∼ 3e ∼ 3b ∼3d > 3a (see
Table 3). Basically, these data are in agreement with the chromo-
fluorogenic behaviour of the receptors and with the expected
basicity of anions in acetonitrile (i.e., F− > CN− > AcO−
>
H2PO4−, Cl−, HSO4−, SCN−, NO3−, Br−, I−). Thus, the most
basic anions fluoride and cyanide induced substantial spectro-
scopic changes for all the receptors, whereas acetate generally
showed more minor changes in the optical properties of the
receptors.
Quantum mechanical studies
One way of describing the hydrogen bond-donating or -accepting
ability of a molecule in a particular group can be accessed by
gas-phase deprotonation energy studies determined by quantum
chemical calculations by subtracting the energy of the receptor
alone from that of the deprotonated form. For these studies,
receptors 3a–f containing furyl heterocycles were selected in
order to obtain data that would be comparable. Calculations were
carried out using a PM3 semi-empirical model. These thiosemi-
carbazone receptors contained two N–H groups and the deproto-
nation studies were performed by assuming that both protons
could be eliminated. The data in Table 3 strongly suggest that
the most acidic one was that attached to the imine carbon directly
bonded to the furyl heterocycle (the more negative the value of
the difference, the stronger the hydrogen-bond donor character).
However, these results obtained from theoretical calculations
Electrochemical studies in the presence of fluoride
The electrochemical behaviour of receptor 3b was studied alone
(5 × 10−4 mol dm−3) and in the presence of fluoride anion in
acetonitrile using platinum as the working electrode and [Bu4N]-
[ClO4] as the supporting electrolyte (see Fig. 9). Receptor 3b
showed a poorly defined irreversible oxidation band sweeping to
anodic potentials at 0.7 V. Addition of 1 equiv. of fluoride
induced an intensity increase, a small shift of the original oxi-
dation band (band 1) and the appearance of a new oxidation
band (band 2) at 0.2 V. Addition of 10 equiv. of fluoride
enhanced the intensity of both bands. The fact that band 1 did
not completely disappear with excess fluoride suggests the pres-
ence of a complex electrochemical mechanism involving both
electrochemical and chemical reactions.
Moreover, Fig. 10 shows the plot showing the current of
band 1 versus the equivalents of the fluoride added in the 3b
receptor. As observed, an almost linear increase took place up to
2 equiv. This behaviour is in agreement with fluoride reaction
with 3b, inducing deprotonation and the formation of the F2H−
species.
1
contrast with the apparent conclusion of the H NMR titrations,
which suggested that deprotonation occurred at the Hg proton.
The literature describes similar contradictory results obtained
from the theoretical and experimental NMR data.14
Despite this apparent contradiction, the theoretical calculations
roughly agree with the chromogenic behaviour observed for the
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whereas the addition of fluoride also induces the growth of a
new oxidation band at 0.2 V. The observed response toward
basic anions of the receptors described in this paper clearly
resembles that obtained with other derivatives containing hydro-
gen bonding binding sites (ureas, thioureas and amides). The
selectivity trend is the same and only basic anions were able to
induce a chromo-fluorogenic response. Despite the lack of
response of these receptors in aqueous environments, the ease of
synthesis of thiosemicarbazones opens the possibility to design
more complex and pre-organized neutral receptors for anions
with enhanced selectivity and applicability in aqueous
environments.
Fig. 9 Cyclic voltammogram of receptor 3b (5 × 10−4 mol dm−3) in a
solution of 1 × 10−2 mol dm−3 [Bu4N][ClO4]/acetonitrile alone (left)
with 1 (centre) and 10 (right) equiv. of F− anion at the scan rate of
Experimental section
20 mV s−1
.
Materials and methods
Thin-layer chromatography was carried out on 0.25 mm thick
precoated silica plates (Merck Fertigplatten Kieselgel 60F254).
All the melting points were measured on a Gallenkamp melting
point apparatus. NMR spectra were obtained on a Varian Unity
Plus Spectrometer at an operating frequency of 300 MHz for
1H and 75.4 MHz for 13C or with a Bruker Avance III 400 at an
operating frequency of 400 MHz for 1H and 100.6 MHz for
13C, using the solvent peak as an internal reference. Solvents are
indicated in parentheses before the chemical shift values (δ rela-
tive to TMS and given in ppm). The IR spectra were run on a
FTIR Perkin-Elmer 1600 spectrophotometer in Nujol. The
elemental analyses were carried out on a Leco CHNS 932 instru-
ment. Mass spectrometry analyses were performed at the C.A.C.
T.I. – Unidad de Espectrometria de Masas of the University of
Vigo, Spain, in a Hewlett Packard 5989 A spectrometer for low
resolution spectra and in a VG Autospec M spectrometer for
high resolution mass spectra. All the solvents were of spectro-
photometrical grade. Air-/water-sensitive reactions were per-
formed in flame-dried glassware under argon. Aldehydes 1a–c,
1e–f and 4-phenyl-3-thiosemicarbazide 2 were purchased from
Sigma-Aldrich and were used without further purification.
Fig. 10 Current (A) of oxidation band 1 of 3b versus the equivalents
of F− added.
Conclusions
A family of novel heterocyclic thiosemicarbazones containing
furyl moieties (derivatives 3a–f and 4) has been prepared and
characterized, and their interactions with anions have been
studied via UV-Vis and fluorescence titrations, quantum chemi-
cal calculations and electrochemical techniques. The thiosemi-
carbazone dyes show a modulation of their donor hydrogen-
bonding abilities as a function of the electronic nature of the
attached chemical groups. Two distinctive chromo-fluorogenic
behaviours in the presence of anions in acetonitrile solutions are
observed. The more basic anions fluoride and cyanide are
capable of inducing dual coordination–deprotonation for all the
receptors studied, whereas acetate and dihydrogen phosphate
display poorer coordination ability, and deprotonation is
observed only upon the addition of large amounts of anion.
Coordinative hydrogen-bonding interactions result in a slight
bathochromic shift, while deprotonation is indicated by the
appearance of a new band at ca. 400–450 nm. The fluorescence
studies evidence that hydrogen-bonding interactions become
visible through the enhancement of the emission band, whereas
deprotonation induces the appearance of a new red-shifted emis-
sion. The PM3 studies are basically in agreement with the exper-
imental behaviour. The electrochemical studies carried out with
receptor 3b show an irreversible oxidation process at 0.7 V,
General procedure for the synthesis of formyl-furans 1d and 1g
through Suzuki cross-coupling
5-Bromofuran-2-carbaldehyde (1.2 mmol) was coupled with
4-ethoxyphenylboronic acid or with 4-formylphenylboronic acid
(1.6 mmol), in a mixture of DME (15 mL) and aqueous 2 mol
dm-3 Na2CO3 (1 mL) and Pd(PPh3)4 (6 mol%) at 80 °C in an
argon atmosphere for 5–12 h. After cooling, the mixture was
filtered. Ethyl acetate and a saturated solution of NaCl were
added and the phases were separated. The organic phase was
washed with water (3 × 50 mL) and with an aqueous solution of
NaOH (10%). The organic phase obtained was dried (MgSO4),
filtered and solvent removal gave a crude mixture which was
submitted to column chromatography on silica with increasing
amounts of diethyl ether in light petroleum as an eluent, thus
affording the coupled products.
5-(4′-Ethoxyphenyl)furan-2-carbaldehyde (1d).15 Yellow solid
(75%). Mp: 120.1–122.3 °C. IR (Nujol) ν 1670 (CvO), 1608,
1291, 1254, 1119, 1041, 1029, 959, 919, 838, 797, 772 cm−1
.
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1H NMR (CDCl3) δ 1.39 (t, 3H, J = 7.2 Hz, CH3), 4.02 (q, 2H,
J = 7.2 Hz, CH2), 6.66 (d, 1H, 3H, J = 3.6 Hz, 4-H), 6.89 (dd,
2H, J = 6.4 and 2.0 Hz, H3′ and H5′), 7.25 (d, 1H, J = 3.6 Hz,
H3), 7.69 (dd, 2H, J = 6.4 and 2.0 Hz, H2′ and H6′), 9.54 (s,
1H, CHO). 13C NMR (CDCl3) δ 14.54 (CH3), 63.46 (CH2),
106.10 (C4), 114.17 (C3′ and C5′), 121.38 (C5), 124.32 (C3),
126.78 (C2′ and C6′), 151.37 (C2), 159.72 (C1′), 160.12 (C4′),
176.60 (CHO). MS (EI) m/z (%): 216 (M+, 100), 188 (93), 187
(35), 160 (33), 131 (43), 77 (17). HRMS: (EI) m/z (%) for
C13H12O3; calcd 216.079; found 216.078.
C 49.65, H 3.47, N 19.30, S 11.05; found C 49.24, H 3.53, N
19.18, S 11.11.
4-Phenyl-1-((5-phenylfuran-2-yl)methylene)thiosemicarbazone.
3c was obtained as a yellow solid (76%). Mp: 176.0–176.8 °C.
1H NMR (DMSO-d6): δ = 7.14 (d, J = 3.3 Hz, 1H, H3′),
7.18–7.23 (m, 2H, H4 and H4′), 7.32–7.47 (m, 5H, H3′′, H4′′,
H5′′, H3 and H5), 7.58 (br d, J = 7.5 Hz, 2H, H2 and H6), 7.83
(br d, J = 6.9 Hz, 2H, H2′′ and H6′′), 8.09 (s, 1H, –CHvN),
9.93 (s, 1H, SvC–NH), 11.89 (s, 1H, CvN–NH) ppm.
13C NMR (DMSO-d6): δ = 108.5 (C3′), 115.8 (C4′), 124.0 (C2′′
and C6′′), 125.3 (C4), 125.7 (C2 and C6), 128.1 (C3 and C5),
128.3 (C4′′), 129.0 (C3′′ and C5′′), 129.5 (C1′′), 132.4
(–CHvN), 139.0 (C1), 148.9 (C5′), 154.8 (C2′), 175.6 (CvS)
ppm. IR (Nujol) ν 3270, 3147, 1622, 1595, 1553, 1530, 1491,
5-(4′-Formylphenyl)furan-2-carbaldehyde (1g). Orange solid
(91%). Mp: 124.6–126.0 °C. IR (Nujol) ν 1659 (CvO), 1602,
1
1309, 1157, 1117, 1093, 1020, 966, 946, 810, 722 cm−1. H
NMR (CDCl3) δ 7.01 (d, 1H, J = 3.6 Hz, H4), 7.36 (d, 1H, J =
3.6 Hz, H3), 7.98 (m, 4H, H2′, H6′, H3′ and H5′), 9.72 (s, 1H,
CHO), 10.05 (s, 1H, CHO). 13C NMR (CDCl3) δ 110.0 (C4),
123.0 (C3), 125.6 (C2′ and C6′), 130.3 (C3′ and C5′), 134.1
(C1′), 136.5 (C4′), 152.7 (C2), 157.4 (C5), 177.5 (CHO), 191.3
(CHO). MS (EI) m/z (%): 200 (M+, 100), 199 (84), 171 (18),
143 (23), 115 (56). HRMS: (EI) m/z (%) for C12H8O3; calcd
200.047; found 200.048.
1259, 1188, 1092, 1026, 980, 922, 908, 754, 685 cm−1
.
C18H15N3O5S (321.09): calcd C 67.27, H 4.70, N 13.07, S 9.98;
found C 67.19, H 4.76, N 12.91, S 9.65.
1-((5-(4-Ethoxyphenyl)furan-2-yl)methylene)-4-phenylthio-
semicarbazone. 3d was obtained as a yellow solid (78%). Mp:
1
178.8–179.9 °C. H NMR (DMSO-d6): δ = 1.32 (t, J = 7.2 Hz,
3H, OCH2CH3), 4.05 (q, J = 7.2 Hz, 2H, OCH2CH3),
6.96–7.01 (m, 3H, H3′, H3′′ and H5′′), 7.13 (d, J = 3.6 Hz, 1H,
H4′), 7.17–7.23 (m, 1H, H4), 7.37 (br t, J = 7.2 Hz, 2H, H3 and
H5), 7.58 (br d, J = 7.2 Hz, 2H, H2 and H6), 7.76 (dd, J =
6.9 and 2.1 Hz, 2H, H2′′ and H6′′), 8.01 (s, 1H, –CHvN), 9.89
(s, 1H, SvC–NH), 11.84 (s, 1H, CvN–NH) ppm. 13C NMR
(DMSO-d6): δ = 14.6 (OCH2CH3), 63.2 (OCH2CH3), 106.7
(C3′), 114.8 (C3′′ and C5′′), 116.2 (C4′), 122.2 (C1′′), 125.3
(C4), 125.6 (C2 and C6), 125.7 (C2′′ and C6′′), 128.1 (C3 and
C5), 132.5 (–CHvN), 139.0 (C1), 148.1 (C5′), 155.2 (C2′),
158.7 (C4′′), 175.5 (CvS) ppm. IR (Nujol) ν 3339, 3133, 1621,
1606, 1548, 1505, 1269, 1251, 1219, 1176, 1116, 1037, 975,
919, 833, 786, 740 cm−1. C20H19N3O2S (365.12): calcd
C 65.73, H 5.24, N 11.50, S 8.77; found C 65.23, H 5.21, N
11.49, S 8.69.
General procedure for the synthesis of heterocyclic
phenylthiosemicarbazones 3–4
Equal amounts (0.4 mmol) of the appropriate aldehyde and thio-
semicarbazide were dissolved in MeOH (30 mL) at room temp-
erature. A solution was obtained, which was stirred overnight.
Compounds were precipitated as microcrystalline solids, and
were collected by suction filtration, washed with cold MeOH
and diethyl ether, then dried by vacuum. Further recrystalliza-
tions using CHCl3–petroleum ether mixtures were performed
when was necessary.
1-((5-Bromofuran-2-yl)methylene)-4-phenylthiosemicarbazone.
3a was obtained as a yellow solid (76%). Mp: 149.5–150.8 °C.
1H NMR (DMSO-d6): δ = 6.76 (d, J = 3.9 Hz, 1H, H3′), 7.10
(d, J = 3.9 Hz, 1H, H4′), 7.15–7.21 (m, 1H, H4), 7.34 (br t, J =
7.2 Hz, 2H, H3 and H5), 7.55 (br d, J = 7.2 Hz, 2H, H2 and
H6), 7.99 (s, 1H, –CHvN), 9.88 (s, 1H, SvC–NH), 11.85 (s,
1H, CvN–NH) ppm. 13C NMR (DMSO-d6): δ = 114.5 (C3′),
115.6 (C4′), 124.3 (C5′), 125.3 (C4), 125.5 (C2 and C6), 128.1
(C3 and C5), 131.67 (–CHvN), 138.9 (C1), 151.4 (C2′), 175.8
(CvS) ppm. IR (Nujol) ν 3332, 3132, 1593, 1558, 1538, 1515,
1-((5-(4-Bromophenyl)furan-2-yl)methylene)-4-phenylthio-
semicarbazone. 3e was obtained as a yellow solid (87%). Mp:
1
197.3–198.7 °C. H NMR (DMSO-d6): δ = 7.18–7.23 (m, 3H,
H3′, H4′ and H4), 7.37 (br t, J = 8.0 Hz, 2H, H3 and H5), 7.58
(br d, 1H, J = 8.0 Hz, 2H, H2 and H6), 7.63 (dd, J = 6.4 and
2.0 Hz, 2H, H2′′ and H6′′), 7.78 (dd, J = 6.4 and 2.0 Hz, 2H,
H3′′ and H5′′), 8.08 (s, 1H, –CHvN), 9.92 (s, 1H, SvC–NH),
11.89 (s, 1H, CvN–NH) ppm. 13C NMR (DMSO-d6): δ =
109.2 (C3′), 115.8 (C4′), 121.2 (C4′′), 125.3 (C4), 125.7 (C2
and C6), 125.9 (C3′′ and C5′′), 128.1 (C3 and C5), 128.6 (C1′′),
131.9 (C2′′ and C6′′), 132.2 (–CHvN), 139.0 (C1), 149.3 (C5′),
153.6 (C2′), 175.7 (CvS) ppm. IR (Nujol) ν 3287, 3143, 1683,
1667, 1594, 1552, 1504, 1445, 1265, 1197, 1974, 1021, 1008,
926, 822, 785, 766, 735 cm−1. MS (ESI): m/z (%) = 402 (M + H
1448, 1274, 1266, 1205, 1125, 1016, 920, 781, 739, 689 cm−1
C12H10BrN3OS (322.97): calcd C 44.46, H 3.11, N 12.96,
S 9.89; found C 44.33, H 3.12, N 12.93, S 9.81.
.
1-((5-Nitrofuran-2-yl)methylene)-4-phenylthiosemicarbazone.
3b was obtained as a yellow solid (81%). Mp: 188.0–188.7 °C.
1H NMR (DMSO-d6): δ = 7.20–7.25 (m, 1H, H4), 7.38 (br t, J =
7.8 Hz, 2H, H3 and H5), 7.49–7.55 (m, 3H, H3′, H2 and H6),
7.82 (d, J = 3.9 Hz, 1H, H4′), 8.07 (s, 1H, –CHvN), 10.18 (s,
1H, SvC–NH), 12.23 (s, 1H, CvN–NH) ppm. 13C NMR
(DMSO-d6): δ = 113.5 (C3′), 115.2 (C4′), 125.7 (C4), 125.9 (C2
and C6), 128.2 (C3 and C5), 130.2 (–CHvN), 138.7 (C1),
151.6 (C5′), 152.6 (C2′), 176.3 (CvS) ppm. IR (Nujol) ν 3313,
3135, 1554, 1529, 1514, 1344, 1251, 1188, 1098, 1015, 964,
810, 760, 741, 693 cm−1. C12H10N4O3S (290.05): calcd
+
81Br, 100), 400 (M + H + 79Br, 100), 399 (M+, 82), 370 (41),
368 (41). HRMS (ESI): calcd for C18H1581BrN3OS 402.00929,
found 402.00905; calcd for C18H1579BrN3OS 400.0114, found
400.0111.
1-((5-(4-Nitrophenyl)furan-2-yl)methylene)-4-phenylthiosemi-
carbazone. 3f was obtained as a yellow solid (96%). Mp:
1
205.4–206.8 °C. H NMR (DMSO-d6): δ = 7.19–7.25 (m, 1H,
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H4), 7.28 (d, J = 3.9 Hz, 1H, H3′), 7.38 (br t, J = 7.8 Hz, 2H,
H3 and H5), 7.48 (d, J = 3.9 Hz, 1H, H4′), 7.57 (br d, J =
7.8 Hz, 2H, H2 and H6), 8.05–8.11 (m, 3H, H2′′, H6′′ and
–CHvN), 8.28 (dd, J = 7.2 and 2.1 Hz, 2H, H3′′ and H5′′), 9.99
(s, 1H, SvC–NH), 12.00 (s, 1H, CvN–NH) ppm. 13C NMR
(DMSO-d6): δ = 112.6 (C3′), 115.7 (C4′), 124.4 (C3′′ and C5′′),
124.6 (C2′′ and C6′′), 125.5 (C4), 125.8 (C2 and C6), 128.2
(C3 and C5), 131.8 (–CHvN), 135.2 (C1′′), 138.9 (C1), 146.3
(C4′′), 151.0 (C5′), 152.4 (C2′), 175.8 (CvS) ppm. IR (Nujol) ν
3316, 3135, 1600, 1592, 1552, 1510, 1341, 1265, 1212, 1201,
the supporting electrolyte and a scan rate of 20 mV s−1 in a
thermostated cell at 25 °C.
Theoretical studies
Quantum chemical calculations at the semi-empirical level
(PM3, within restricted Hartree–Fock level) were carried out in
vacuum with the aid of Hyperchem V6.03. The Polar–Ribiere
algorithm was used for optimization. The convergence limit and
the RMS gradient were set to 0.01 kcal mol−1. Stability con-
stants were estimated with the HypSpec Software V1.1.18 using
the data of the titration of receptors with selected anions.
1114, 1084, 1029, 809, 849, 798, 711, 693, 637 cm−1
.
C18H14N4O3S (366.08): calcd C 59.01, H 3.85, N 15.29, S 8.75;
found C 58.39, H 3.92, N 15.25, S 8.77.
1,1-((5-Phenylfuran-2-yl)methylene)-bis-4-phenylthiosemicar-
Acknowledgements
bazone. 4 was obtained as a yellow solid (90%). Mp:
1
We thank the Spanish Government (project MAT2009-14564-
C04-01) and the Generalitat Valenciana (project PROMETEO/
2009/016) for support. We are also grateful to the Fundação para
a Ciência e Tecnologia (Portugal) and FEDER-COMPETE for
financial support through the Centro de Química – Universidade
do Minho, Project PEst-C/QUI/UI0686/2011 (F-COMP-01-
0124-FEDER-022716) and a Post-doctoral grant to R.M.F.
Batista (SFRH/BPD/79333/2011). The NMR spectrometer
Bruker Avance III 400 is part of the National NMR Network and
was purchased within the framework of the National Program for
Scientific Re-equipment, with funds from FCT. The authors are
also indebted to the programme “Acções Integradas Luso-
Espanholas/CRUP”, for bilateral agreement number E-144/10.
Thanks also go to the Fundación Carolina and UPNFM-Honduras
for a doctoral grant to L.E. Santos-Figueroa and the Spanish
Ministry of Science and Innovation for an FPU grant to M.E.
Moragues.
203.9–204.8 °C. H NMR (DMSO-d6): δ = 7.18–7.23 (m, 3H,
2 × (H4 and H4′)), 7.27 (d, J = 3.6 Hz, 1H, H3′), 7.37 (br t, J =
7.9 Hz, 4H, 2 × (H3 and H5)), 7.55–7.62 (m, 4H, 2 × (H2
and H6)), 7.88 (d, J = 8.4 Hz, 2H, H2′′ and H6′′), 7.97 (d, J =
8.4 Hz, 2H, H3′′ and H5′′), 8.10 (s, 1H, –CHvN), 8.16 (s, 1H,
–CHvN), 9.96 (s, 1H, SvC–NH), 10.15 (s, 1H, SvC–NH),
11.86 (s, 1H, CvN–NH), 11.91 (s, 1H, CvN–NH) ppm.
13C NMR (DMSO-d6): δ = 109.7 (C3′), 115.9 (C4′), 124.1 (C2′′
and C6′′), 125.3 (C4), 125.4 (C4), 125.5 (C2 and C6), 126.0 (C2
and C6), 128.0 (C3 and C5), 128.1 (C3 and C5), 128.2 (C3′′ and
C5′′), 130.5 (C1′′), 132.2 (–CHvN), 133.7 (C4′′), 138.9 (C1),
139.0 (C1), 142.2 (–CHvN), 149.4 (C2′), 154.3 (C5′), 175.6
(CvS), 176.0 (CvS) ppm. IR (Nujol) ν 3322, 3300, 3158,
1598, 1559, 1524, 1449, 1329, 1261, 1195, 1096, 1024, 943,
919, 747, 693 cm−1. MS (ESI): m/z (%) = 499 (M + H+, 100),
467 (24), 437 (14), 415 (25), 350 (16), 298 (9). HRMS (ESI):
calcd for C26H22N6OS2 499.1369, found 499.1364.
Notes and references
Spectroscopic studies
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,
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