Study on the synthesis and molecular recognition of new receptors for selective complexation of carboxylic acids

Article abstract of DOI:10.1016/j.tet.2010.01.066

A new synthetic method based on the synthesis of unsymmetrical thioureas followed by double S-alkylation reaction by xylylene dibromides was used to obtain isothiouronium receptors. Their binding abilities to acetate, succinate and maleate anions were evaluated by UV-vis spectroscopic titrations in such solvents as water, acetonitrile, methanol and mixtures of acetonitrile/methanol (1:1, v/v). For simple receptor 4 with one isothiouronium group, no selectivity was observed in the complexation of the anions studied. Receptors (R) 5a-c with two thiouronium groups are able to form with all the anions studied (A) not only stable complexes of 1:1 stoichiometry but also other possessing structure of the type A_nR_m. The most reliable values of stability constants are for systems of the type maleate anion-receptor 5 and acetate-receptor 5b. However, the best selectivity in the mixed solvents is demonstrated by anion-5c system. The study indicates also that particularly 5c is preferred as a chemosensor for the maleate anion. The obtained results suggest that subtle changes in the receptor structure lead to different binding modes towards anions.

Full text of DOI:10.1016/j.tet.2010.01.066

Tetrahedron 66 (2010) 2486–2491
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Study on the synthesis and molecular recognition of new receptors for selective
complexation of carboxylic acids
,
Maja Or1owska a, Micha1 Mroczkiewicz b, Katarzyna Guzow a, Ryszard Ostaszewski c
,
*
,
Andrzej M. K1onkowski a
*
a
´
´
Faculty of Chemistry, University of Gdansk, Sobieskiego 18, 80-952 Gdansk, Poland
b Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland
c Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-229 Warsaw, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
A new synthetic method based on the synthesis of unsymmetrical thioureas followed by double S-al-
kylation reaction by xylylene dibromides was used to obtain isothiouronium receptors. Their binding
abilities to acetate, succinate and maleate anions were evaluated by UV–vis spectroscopic titrations in
such solvents as water, acetonitrile, methanol and mixtures of acetonitrile/methanol (1:1, v/v). For simple
receptor 4 with one isothiouronium group, no selectivity was observed in the complexation of the anions
studied. Receptors (R) 5a–c with two thiouronium groups are able to form with all the anions studied (A)
not only stable complexes of 1:1 stoichiometry but also other possessing structure of the type AnRm. The
most reliable values of stability constants are for systems of the type maleate anion-receptor 5 and
acetate-receptor 5b. However, the best selectivity in the mixed solvents is demonstrated by anion-5c
system. The study indicates also that particularly 5c is preferred as a chemosensor for the maleate anion.
The obtained results suggest that subtle changes in the receptor structure lead to different binding
modes towards anions.
Received 16 October 2009
Received in revised form 9 December 2009
Accepted 18 January 2010
Available online 22 January 2010
Keywords:
Thiouronium salts
Anion receptors
Pyrene
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
hydrogen bonding structure involved in the anion-ligand complex
in order to achieve the best sensitivity and selectivity.
The great interest devoted by chemists to chemical sensors is
comprehensible taking into account that these species can offer the
possibility to monitor in situ, in real time and real space, the con-
centrations of analytes for many different purposes. They have
important applications in environmental monitoring,1 process
control,2 food and beverage analyses,3 medical diagnosis4 and so
on. A fruitful approach to the design and synthesis of efficient
sensor device is the development of molecular entities, referred to
as chemosensors, able to recognise the target analyte with desire
affinity and selectivity, and presenting an efficient signal trans-
duction mechanism.5
The selective recognition of carboxylic acid oxoanions takes
place by a combination of hydrogen bonds and electrostatic in-
teractions.6–8 Using these binding forces as well as others, some
synthetic receptors for oxoanions in strongly solvating solvents
have recently been developed by several research groups.7 Many
years ago thiouronium salts have been used as reagents for the
identification of organic acids.8 Yeo and Hong9 showed that the
thiouronium group generated by S-alkylation of the thiourea group
possesses a relatively larger dipole moment and enhances acidity of
thiourea NH residues and therefore could function as a carboxylic
acid anion binder better than the thiourea group.
Nowadays, among different target analytes, organic carboxylic
and dicarboxylic acids are points of interest. When designing the
structure of a chemosensor for anions, one has to take into account
not only some photophysical parameters but also a type of
For efficient complexation of dicarboxylic acid anions, special
receptors are required. In the chemical structure of these receptors,
two thiouronium groups should be present in precisely defined
positions as already discussed in the literature.10 Therefore, the
synthesis of receptors should give the possibility to define the
distance between thiouronium groups. This type of receptor
showed UV–vis spectral changes on complexation with di-
carboxylic acid anions in spite of lacking conjugation between the
chromophore and the binding sites, in polar organic solvents such
as acetonitrile. It is also important to compare the complexation
* Corresponding authors. Tel.: þ48 22 343 2120 (R.O.); tel.: þ48 58 523 5400
(A.M.K.).
E-mail addresses: rysza@icho.edu.pl (R. Ostaszewski), aklonk@chem.ug.gda.pl
(A.M. K1onkowski).
0040-4020/$ – see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.01.066

M. Orłowska et al. / Tetrahedron 66 (2010) 2486–2491
2487
properties of receptors prepared for mono- and dicarboxylic acid
anions in order to find receptors selective towards dicarboxylic acid
anions.
N2H4
Pd/C
PhSCN
Py
Ph
Py NO2
Py NH2
N
H
N
H
2
1
3
A common problem in the synthesis of new receptors and fur-
ther complexation studies is associated with existing synthetic
procedures. Therefore, simple and efficient synthetic methods are
of great importance for the scientific community. In most cases, the
synthesis of bis-thiouronium receptors III is based on reaction of
diamines and arylisocyanates (Scheme 1).9,11 Products II are key
elements in this synthesis. Double S-alkylation of these bi-
functional receptors II with alkyl bromides leads to respective
thiouronium salts III, which can be used for complexation studies.
X
BnBr
Br
Br
+
Ph
MeNO2
Ph
H
MeNO2
N
Ph
+
H
Bn
S
H
Py
Br-
N
N
N
H
X
+
S
2 Br-
S
Py
Py
N
H
4
N
H
5
5a X = 1,2- (CH2)2Ph, 58%
5b X = 1,3- (CH2)2Ph, 58%
5c X = 1,4- (CH2)2Ph, 85%
Py =
R
Scheme 3. Synthesis of bis-thiouronium salts based on xylylene structures.
S
S
In the model reaction between thiourea 3 and benzyl bromide,
the product isothiouronium salt 4 was obtained in 95% yield. The
product precipitates from reaction mixture what simplifies the
experimental procedure. In the next step of our studies the reaction
with dibromides was performed. As the substrates, compound 3
and o-, m- and p-xylylene dibromides were used. Xylylene dibro-
mides are readily available and offer full control of the structure of
receptors with precisely increasing distances between iso-
thiouronium groups. In nitromethane solution, at 80 ꢀC, the bis-
thiouronium receptors 5a, b and c were obtained in 58, 58 and
85% yields, respectively. Again, we observed precipitation of the
products from reaction mixtures. A strong electrostatic interaction
between thiouronium groups lowers the yields of reaction for o-
and m-xylylene dibromides. Longer distances between functional
groups diminished the electrostatic interaction and increased the
yield up to 85% for compound 5c.
In the next steps of our studies, the complexation of acetate,
succinate and maleate anions (as their tetrapropylammonium salts)
with the receptors obtained was investigated by UV–vis spectro-
scopic titrations in water, aprotic MeCN, MeOH and mixed MeCN/
MeOH (1:1, v/v). In the case of aqueous solutions no distinct changes
in absorption spectra of receptors studied are observed, while in
MeOH solutions the spectral changes are more distinct but remain
ambiguous. An increase of the anion concentration in each of the
receptor–anion systems in MeCN/MeOH solutions up to [anion]/
[receptor]¼5 causes an increase of the absorption bands at 282, 357,
367 and 386 nm as well as a decrease at about 243, 277, 328 and
345 nm with isosbestic points at 279, 309 and 350 nm (Fig. 1). The
well-defined red shift of the charge transfer bands (at 243 and
344 nm) is probably a result of the electron density transfer to the
thiouronium moiety, which makes the intensity of the dipole
HN
HN
NHAr
HN
NHAr
NH2
NH2
+
2 ArNCS
2 R-Br
2 Br-
+
NHAr
II
HN
R
NHAr
III
I
S
S
Scheme 1. The synthesis reactions of the bis-thiouronium salt III.
Here we propose a new method based on the reaction of aryl
amines with alkyl or arylisocyanates (Scheme 2). In the reaction of
primary aromatic or aliphatic amines and isothiocyanates, asym-
metric thioureas IV can be obtained, which might be used as sub-
strates for subsequent reaction with
a,u-dibromides leading to
target structures V. Aromatic amines can be used for the synthesis
of new receptors, commercially available or prepared according to
standard synthetic procedures.
NHR
+
Br-
S
S
ArNH2
+
RNCS
Br
Br
NHAr
NHAr
Br-
+
NHR
ArHN
NHR
S
IV
V
Scheme 2. Proposal of the synthesis of the bis-thiouronium salts V.
For our studies, aminopyrene was chosen as a good fluorescent
substrate readily available in large quantities. Thus, we report here
the synthesis of pyrene chemosenors and their complexation stud-
ies with carboxylic (acetate, succinate and maleate) anions in water,
acetonitrile (MeCN), methanol (MeOH) or MeCN/MeOH (1:1, v/v).
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
2. Results and discussion
The method used for the synthesis of receptors is based on two
reactions: formation of unsymmetrical thioureas followed by
double S-alkylation of the products obtained. Since a very large
number of aromatic amines is available this approach opens
a convenient way for the synthesis of receptors of general structure
V (Scheme 2).
The key compound in the synthetic strategy is thiourea 3 that
was prepared in a three-step synthesis (Scheme 3). Nitration of
pyrene gave 1-nitropyrene (1) as yellow crystals in 51% yield. Re-
duction (Pd/C) of this compound using hydrazine monohydrate led
to 1-aminopyrene (2) in 56% yield. Both reactions can be readily
performed on large scale. The product obtained was used as
a substrate for next reaction with phenyl isothiocyanate, which lead
to compound 3 in 74% yield.
250
300
350
400
450
Wavelength λ / nm
Figure 1. UV–vis spectral changes of the receptor upon the addition of acetate, mal-
eate or succinate anion in MeCN/MeOH (1:1, v/v).

2488
M. Orłowska et al. / Tetrahedron 66 (2010) 2486–2491
increase and shifts the charge transfer band to longer wavelength.
The presence of sharp isosbestic points indicate that some authentic
H-bonded complexes of different stoichiometry co-exist in the so-
lution. This is additionallyconfirmed by the absorbance–absorbance
(A–A) and absorbance-[anion]/[receptor] plots in MeCN or MeCN/
MeOH solutions.
For the three selected anions and receptors 5 in the mixture of
MeCN and MeOH, the A–A plots (Fig. S1, Supplementary data) ex-
hibit distinct two linear intersecting segments, indicating that the
system involves two titration steps.12 Unfortunately, the results
obtained for receptors 4 are unresolved.
been considered in calculations. Thus, the maleate-5a system is
characterized inpractice bythe 1:1 and 3:1 complexes, whileacetate
or succinate anions with the same receptor form complexes of
stoichiometry 1:1 and 2:1 or 1:1 and 1:2, respectively. The changes
of the concentration of the complexes with different stoichiometries
during titration for the selected complex systems are presented in
Figure S2 (Supplementary data). The standard deviations of the
higher order complexes are higher than those of 1:1 complexes.
However, the stability constants of the 1:1 species are over the re-
liability limit for the UV–vis spectroscopy equal to 7 (cf. in Table 1).
Acetate anion with receptor 5b forms a 1:1 complex where log
The absorbance vs [anion]/[receptor] plots (Fig. 2) for the
above-mentioned complex systems are composed of two linear
segments, which intersect at about 1.5 M ratio for [maleate]:[5a]
and [acetate]:[5b] as well as about 1.0 M ratio for [succina-
te]:[5c]. In all cases, a small inflection is also observed for higher
molar ratio. These effects confirm the results shown in Figure S1
(Supplementary data) and indicate on the presence of complexes
with various stoichiometries.12 Contribution of the complexes
with various stoichiometries to the absorption spectra is suffi-
cient enough for the calculation of stability constants of each
complex formed in the anion-5a–c systems (Table 1).
b is reliable because its value is lower than 7 and has low confi-
dence interval (entry 5 in Table 1). Equally valuable are the stability
constants of the complexes with maleate anion. It is interesting to
note that log
b value is near the same, within experimental error,
for maleate complexes 1:1 with the receptors, while the stability of
the 2:1 complexes with 5b and c slightly decreases with the dis-
tance between thiouronium groups in the receptor (entries 7 and
10 in Table 1). The higher constant value the more effective is
charge compensation of the receptors by succinate anions. How-
ever, too high stability constants (above 7) of the 1:1 complexes in
the systems acetate-5a and succinate-5a–c are not reliable enough
to compare the charge compensation in those systems with others.
The stability constants calculated for each of the studied com-
plex systems are collected in Table 1.
Then, for succinate-5b system log
b of both complexes is charged
A relatively low standard deviation of the calculated binding
constants is a result of the fact that the formation of higher order
complex, the presence of which is suggested in the plots (Fig. 2), has
with rather high experimental error (entry 5 in Table 1).
As observed, the acetate anion can form with receptors 5a or 5b
complexes of 2:1 or 3:2 stoichiometries besides the 1:1 species. On
0.48
0.50
0.48
0.46
0.44
0.42
0.40
0.635
A
0.630
0.47
0.625
0.620
0.46
0.615
0.45
0.610
0.605
0.44
0.600
0.595
0.43
0
1
2
3
4
0
1
2
3
4
0
1
2
3
4
[Anion] / [Receptor]
[Anion] / [Receptor]
[Anion] / [Receptor]
0.63
0.62
0.61
0.60
0.59
0.58
0.57
0.56
0.55
0.54
0.80
0.79
0.78
0.77
0.76
0.75
0.74
0.73
0.72
0.71
B
0.60
0.55
0.50
0.45
0.40
0.35
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
[Anion] / [Receptor]
[Anion] / [Receptor]
[Anion] / [Receptor]
0.55
0.50
0.45
0.40
0.35
0.30
0.60
0.58
0.56
0.54
0.52
0.50
0.48
0.46
0.44
0.42
C
0.72
0.70
0.68
0.66
0.64
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
-0.5
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
[Anion] / [Receptor]
[Anion] / [Receptor]
[Anion] / [Receptor]
Figure 2. Absorbance vs [anion]/[5] molar ratio, where the anion and receptor are: (A) [maleate]/[5a], (B) [acetate]/[5b] and (C) [succinate]/[5c].

M. Orłowska et al. / Tetrahedron 66 (2010) 2486–2491
2489
Table 1
Complex stoichiometries and stability constants of the anion-receptor complexes in MeCN/MeOH (1:1 v/v) solution
Entry
Receptor
Anion
Complex stoichiometry
[anion]/[receptor]
Stability constant
log
b
1
2
4
Acetate, Succinate, Maleate
Acetate
d
unresolved
5a
1:1
2:1
1:1
1:2
1:1
3:1
8.09ꢃ0.58
14.46ꢃ0.67
7.16ꢃ0.47
13.98ꢃ0.67
6.31ꢃ0.16
16.04ꢃ0.21
3
4
Succinate
Maleate
5
6
7
5b
5c
Acetate
1:1
3:2
1:1
1:2
1:1
2:1
5.94ꢃ0.34
25.35ꢃ0.27
8.88ꢃ1.48
13.70ꢃ1.50
6.25ꢃ0.12
11.00ꢃ0.27
Succinate
Maleate
8
Acetate
1:1
3:2
1:1
1:2
1:1
2:1
unresolved
22.39ꢃ0.18
8.87ꢃ0.86
14.53ꢃ0.95
6.75ꢃ0.25
10.76ꢃ0.37
9
Succinate
Maleate
10
the contrary, 5c creates only one complex, viz. 3:2 one, with the
mentioned anion. It is presumably due to the distance between
thiouronium groups in 5c molecule, that is, so large that the 1:1
complex cannot be formed.
Complexation of the anions (A) and the receptors (R) shows that
in the case of maleate dianion it is possible to calculate more pre-
cisely the individual stability constants of their A3R or A2R com-
plexes with 5 receptors (entry 4, 7 and 10 in Table 1). The presence
of a small inflexion (at about 2:1 [anion]/[receptor] ratio) on the
plots of absorbance vs [maleate]/[5] molar ratio in Figure 2A and
Figure S3 (Supplementary data) confirms formation of higher order
Among the anions selected to bind with the receptors 5a–c, only
maleate creates complexes with high reliability of log (values below
b
7) and relatively narrow confidence interval. Moreover, the most
favourable situation for selectivity is in the case, if the stability con-
stants of the anion-receptor complexes differ distinctly (i.e., confidence
intervals do not overlap). From this point of view we turn our special
attention to 5c as a receptor, especially suitable for maleate anion.
Unfortunately, for the above-mentioned complex systems with
the receptors 5a–c it is not possible to determine reliable log
b
values in MeCN solutions using UV–vis method since they very
often exceed 7.
1.4
1.2
1.2
1.0
A/R = 1:1
R
1.0
R
A/R = 1:1
0.8
0.8
0.6
0.4
0.2
0.6
A/R = 2:1
0.4
0.2
0.0
A/R = 2:1
0.0
0.0
0.8
1.6
2.4
3.2
0
1
2
3
4
-5
Anion concentration / 10 M
-5
Anion concentration / 10 M
Figure 3. Concentrations of the species vs concentration of maleate anion in the complex systems with receptors: A. 5b and B. 5c.
complexes in the mixed solvent. Meanwhile, as shown in Figure 3
3. Conclusions
and Figure S2A (Supplementary data), the contribution of the
complexes A3R or A2R created with 5a–c is lower than the AR
species up to ca. 4$10ꢁ5 M in each case.
Isothiouronium receptors with pyrene as a chromophore were
synthesized according to a new procedure based on double S-al-
kylation of unsymmetrical thioureas by xylylene dibromides. The
obtained receptors 4 and 5 (as their tetrapropylammonium salts)
were titrated with acetate, succinate and maleate anions. The ob-
served substantial changes in their absorption spectra cause that
the pyrene receptors with thiouronium fragments could be used as
chromophores in the case of acetate and maleate anions. Among
the solvents used only the MeCN/MeOH solvents mixture (1:1, v/v)
supplies optimal conditions for formation of the complexes anion-
receptor as another studied are either too weak (as MeCN) or too
strong (as H2O and MeOH) in the hydrogen bonding competition
For the dianions (succinate and maleate) the AR complex
dominates over the higher order AmRn complexes in the titration
range. Maleate forms AmRn species, where m>n, whereas succinate
complexes of higher order, vice versa, are characterized by m<n
(Table 1). Acetate as monoanion in the complex systems creates
a more complicated situation, viz., for R¼5a complex AR exceeds
A2R in concentration in the narrow range (0.8ꢂ10ꢁ5–1.9ꢂ10ꢁ5 M)
whereas A3R2 complex dominates in the whole titration range.
When R is 5b (Fig. S2B) (Supplementary data) or 5c only complex
A3R2 exists (entry 8 Table 1).

2490
M. Orłowska et al. / Tetrahedron 66 (2010) 2486–2491
and polarity. UV–vis absorption method enables to determine re-
liable log values only for the systems of the type anion-receptor 5
in MeCN/MeOH solutions. Analysis of the stability constants pro-
vides evidence that compound 5c is a favourable receptor for such
dicarboxylic anion as maleate.
reaction was stirred for 22 h. Precipitated product was filtered off
b
and washed by dichloromethane to gave yellow solid of N-phenyl-
N0- -pyrenyl thiourea (361 mg, 1.02 mmol, 74%): mp 191–194 ꢀC;
a
Rf¼0.77 (Hexane/AcOEt¼4:6, v/v); IR (KBr):
n
(cmꢁ1)¼3326 (m),
3106 (m), 2947 (m), 1587 (w), 1536 (s), 1490 (s), 1263 (m), 1244
(m), 1205 (m), 1184 (m), 845 (m), 694 (m); 1H NMR (200 MHz,
4. Experimental
DMSO-d6):
d
¼10.29 (s, 1H, NH), 9.92 (s, 1H, NH), 8.50–8.00 (m,
10H, ArH) 7.59 (d, J¼7.6 Hz, 2H, ArH), 7.36 (t, J¼7.6 Hz, 2H, ArH),
NMR spectra were measured with Varian 200 GEMINI and
Varian 400 GEMINI spectrometers with TMS as internal standard.
TLCs were performed with silica gel 60 (230–400 mesh, Merck) and
silica gel 60 PF254 (Merck). CHN analysis was performed on Perkin–
Elmer 240 Elemental Analyzer whereas CHNS analysis on Heraeus
Vario EL III apparatus. MS spectra were recorded on an API-365
(SCIEX) apparatus. Acetonitrile (MeCN) used in our study was
HPLC grade.
7.15 (t, J¼7.5 Hz, 1H, ArH); 13C NMR (50 MHz, DMSO-d6):
¼181.4,
d
139.6, 133.0, 130.6, 130.5, 129.3, 128.4, 127.5, 127.2, 127.1, 126.7,
126.4, 125.4, 125.2, 124.9, 124.6, 124.1, 122.7. Anal. Calcd for
C23H16N2S: C, 78.38; H, 4.58; N, 7.95. Found: C, 78.39; H, 4.55; N,
7.93.%.
4.1.2.4. Preparation of salt 4. To a suspension of 1-phenyl-3-
pyren-1-yl-thiourea (70 mg, 0.20 mmol) in ethanol (10 ml) benzyl
bromide (26 ml, 0.22 mmol) was added. The mixturewas refluxed for
4.1. Synthesis
4 h. Then solvent was evaporated and residue was washed with
diethyl ether. Yellow crystalline product was filtered off and dried
(102 mg, 0.19 mmol, 95%): mp 120–123 ꢀC; 1H NMR (200 MHz,
4.1.1. Preparation of tetrapropylammonium salts
DMSO-d6):
d
¼8.45–8.05 (m, 8H), 7.95–7.75 (m, 2H), 7.60–7.25 (m,
4.1.1.1. Tetrapropylammonium acetate. To a solution of tetrapro-
pylammonium hydroxide (10 ml of 20% solution in water, 9.8 mmol)
in methanol (10 ml) acetic acid was added (560 ml, 9.83 mmol). After
9H), 7.22 (s, 1H), 4.61 (s, 2H), 3.52 (dd, J¼7.6 Hz, J¼6.0 Hz, 1H). Anal.
Calcd for C30H23BrN2Sþ1.6H2O: C, 65.24; H, 4.78; N, 5.07. Found: C,
65.26; H, 4.90; N, 5.10. ESI-MS: m/z 443 [M]þ. HRMS (ESI) calcd for
C30H23N2S [MꢁBr]þ: requires 443.1582; found: 443.1559.
3 h hygroscopic crystals of tetrapropylammonium acetate were fil-
tered off and dried under vacuum (0.450 g, 1.8 mmol, 18%):
mp>360 ꢀC.
4.1.2.5. Preparation of salt 5a. A suspension of N-phenyl-N0-
a-
pyrenyl thiourea (502 mg, 1.42 mmol) and 1,2-bis(bromomethyl)-
benzene (179 mg, 0.68 mmol) in nitromethane (25 ml) was heated
at 80 ꢀC for 24 h. A green solid precipitated from the reaction
mixture was filtered, washed with hexane and dried under reduced
4.1.1.2. Tetrapropylammonium maleate. To a solution of tetra-
propylammonium hydroxide (20 ml of 20% solution in water,
19.7 mmol) in methanol (10 ml) maleic acid was added (1.141 g,
9.83 mmol). After 3 h hygroscopic crystals of tetrapropylammonium
maleate was filtered off and dried under vacuum (1.164 g, 2.6 mmol,
24%): mp 170 ꢀC (decomp.).
pressure (375 mg, 0.39 mmol, 58%): mp 160–170 ꢀC; IR (KBr):
n
(cmꢁ1)¼3037, 2850, 1599, 1569, 1493, 845; 1H NMR (200 MHz,
DMSO-d6):
d
¼8.45–7.95 (m, 18H), 7.82 (d, J¼9.0 Hz, 2H), 7.60–7.00
(m, 12H), 4.67 (s, 4H), 4.42 (s, 2H), 3.45 (dd, J¼10.9 Hz, J¼4.1 Hz,
2H). Anal. Calcd for C54H40Br2N4S2þ0.5 MeNO2: C, 65.50; H, 4.19; N,
6.31. Found: C, 65.55; H, 3.99, N, 6.43. ESI-MS: m/z 807
[MꢁHBrꢁBr]þ. HRMS (ESI) calcd for C54H39N4S2 [MꢁHBrꢁBr]þ:
requires 807.2616; found: 807.2602.
4.1.1.3. Tetrapropylammonium succinate. To a mixture of tetra-
propylammonium hydroxide solution (20 ml of 20% solution in
water, 19.7 mmol) and methanol (10 ml) succinic acid (1.160 g,
9.83 mmol) was added. After 3 h hygroscopic crystals of tetrapro-
pylammonium succinate were filtered off and dried under vacuum
(1.689 g, 3.44 mmol, 35%): mp 225 ꢀC (decomp.).
4.1.2.6. Preparation of salt 5b. A suspension of N-phenyl-N0-
a-
pyrenyl thiourea (501 mg, 1.42 mmol) and 1,3-bis(bromomethyl)-
benzene (179 mg, 0.68 mmol) in nitromethane (25 ml) was heated to
80 ꢀC for 24 h. A yellow solid precipitated from the reaction mixture
was filtered, washed with hexane and dried under reduced pressure
4.1.2. Preparation of thiouronium salts
4.1.2.1. 1-Nitropyrene (1). To
a solution of pyrene (10 g,
49.4 mmol) in ethyl acetate (140 ml) cupric nitrate trihydrate (16 g,
66.2 mmol) and acetic anhydride (12 ml,126 mmol) were added. The
reaction mixture was stirred at 60 ꢀC for 24 h. Precipitated product
wasfiltered off, washedwith water. Crystallizationfromethyl alcohol
gives yellow crystals of 1-nitropyrene (6.23 g, 25.2 mmol) with 51%
yield: mp 151 ꢀC (lit. 150–152)13; Rf¼0.70 (Hexane/AcOEt¼7:3, v/v).
(375 mg, 0.39 mmol, 58%): mp 165–175 ꢀC; IR (KBr):
n
(cmꢁ1)¼3041,
2850,1600,1568,1493, 846; 1H NMR (200 MHz, DMSO-d6):
d¼8.45–
7.95 (m, 16H), 7.82 (d, J¼9.0 Hz, 4H), 7.60–7.00 (m, 12H), 4.67 (s, 4H),
4.42 (s, 2H), 3.45 (dd, J¼10.9 Hz, J¼4.1 Hz, 2H). Anal. Calcd for
C54H40Br2N4S2þH2OþMeNO2: C, 63.04; H, 4.33; N, 6.68. Found: C,
62.75; H, 3.82; N, 6.85. ESI-MS: m/z 807 [MꢁHBrꢁBr]þ. HRMS (ESI)
calcd for C54H39N4S2 [MꢁHBrꢁBr]þ: requires 807.2616; found:
807.2627.
4.1.2.2. 1-Aminopyrene (2). To
a solution of 1-nitropyrene
(2.25 g, 9.1 mmol) in a mixture of ethanol and toluene (100 ml, 3:1,
v/v) hydrazine monohydrate (2.5 ml, 51 mmol) was added. Then
Pd/C (300 mg, 10 %) was added. The reaction mixture was refluxed
for 25 min, cooled to room temperature and filtered through Celite.
The filtrate was evaporated and residue was crystallized from cy-
clohexane to give yellow needles of 1-aminopyrene (1.108 g,
5.1 mmol) with 56% yield: mp 116–117 ꢀC (lit. 117)14; Rf¼0.40
(Hexane/AcOEt¼7:3, v/v).
4.1.2.7. Preparation of salt 5c. A suspension of N-phenyl-N0-
a-
pyrenyl thiourea (260 mg, 0.74 mmol) and 1,4-bis(bromo-
methyl)benzene (92 mg, 0.35 mmol) in nitromethane (20 ml) was
refluxed for 2.5 h. Yellow crystalline product was filtered off and
driedreduced pressure(288 mg, 0.30 mmol,85%):mp170–177 ꢀC;IR
(KBr):
(200 MHz, DMSO-d6):
n
(cmꢁ1)¼3044, 2856, 2761, 1598, 1568, 1505, 842; 1H NMR
d
¼8.45–8.05 (m, 14H), 7.94 (d, J¼9.2 Hz, 4H),
7.65–7.00 (m, 14H), 4.84 (s, 4H), 4.49 (s, 2H), 3.52 (dd, J¼11.2 Hz,
J¼4.8 Hz, 2H). Anal. Calcd for C54H40Br2N4S2þ0.5 MeNO2: C, 65.50; H,
4.19; N, 6.31. Found: C, 65.49; H, 3.89; N, 6.59. ESI-MS: m/z 807
[MꢁHBrꢁBr]þ. HRMS (ESI) calcd for C54H39N4S2 [MꢁHBrꢁBr]þ: re-
quires 807.2616; found: 807.2583.
4.1.2.3. 1-Phenyl-3-pyren-1-yl-thiourea (3). To a solution of 1-
aminopyrene (2) (300 mg, 1.38 mmol) in dry dichloromethane
(5 ml) phenyl isothiocyanate (250
ml, 2.07 mmol) and N,N-dime-
thylaminopyridyne (10 mg) were added at room temperature. The

M. Orłowska et al. / Tetrahedron 66 (2010) 2486–2491
2491
4.2. UV–vis titration experiments
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We express our gratitude to Prof. Wies1aw Wiczk for his fruitful
comments. FinancialsupportfromtheMinistryofScienceandHigher
Education (Grant 13/COS/2006/03) is gratefully acknowledged.
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Supplementary data associated with this article can be found in
the online version doi:10.1016/j.tet.2010.01.066.