Synthesis of a new tripodal chemosensor based on 2,4,6-triethyl-1,3,5- trimethylbencene scaffolding bearing thiourea and fluorescein for the chromo-fluorogenic detection of anions

Article abstract of DOI:10.1016/j.tetlet.2012.07.039

A tripodal receptor containing thiourea as binding site and fluorescein as signalling subunit has been designed, synthesized and used for the colorimetric detection of basic anions in DMSO solutions.

Full text of DOI:10.1016/j.tetlet.2012.07.039

Tetrahedron Letters 53 (2012) 5110–5113
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of a new tripodal chemosensor based on 2,4,6-triethyl-1,3,5-
trimethylbencene scaffolding bearing thiourea and fluorescein for the
chromo-fluorogenic detection of anions
⇑
⇑
María E. Moragues, Luis E. Santos-Figueroa, Tatiana Ábalos, Félix Sancenón , Ramón Martínez-Máñez
Centro de Reconocimiento Molecular y Desarrollo Tecnológico (IDM), Unidad Mixta Universidad Politécnica de Valencia-Universidad de Valencia, Camino de Vera s/n,
46022, Valencia, Spain
CIBER de Bioingeniería, Biomaterailes y Nanomedicina (CIBER-BBN), Spain
a r t i c l e i n f o
a b s t r a c t
Article history:
A tripodal receptor containing thiourea as binding site and fluorescein as signalling subunit has been
designed, synthesized and used for the colorimetric detection of basic anions in DMSO solutions.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 22 May 2012
Revised 9 July 2012
Accepted 10 July 2012
Available online 15 July 2012
Keywords:
Chromogenic chemosensors
Anion recognition
Tripodal receptor
Prearranged scaffolds
The design of abiotic anion receptors able to display sensing
features has attracted increasing attention due to the key roles
played by these negatively charged species in chemical, biological
via the design of receptors showing multiple coordination sites in
a pre-defined fashion. For instance, some remarkable examples in-
volve the development of anion receptors based on 1,3,5–2,4,6 func-
tionalized benzene scaffoldings with 1,3,5-positions directed to one
face of the ring in order to prepare trifurcate anion receptors con-
taining three arms with coordinating groups in cooperative mode.9
Following our interest in the development of anion chemosen-
1
and environmental processes. Host molecules generally comprise
two subunits, that is, the ‘binding site’ (properly the host, respon-
sible of coordination event) and the ‘signalling subunit’ (in charge
of the transduction event) that are usually attached forming a
2
10
superstructure. In these signalling systems optical outputs are
sors, we report herein the synthesis of an acyclic tripodal recep-
especially attractive with respect to other possible transductions
of the signal, because detection uses cheap, easy-to-handle and
widely extended instrumentation. Apart from fluorescence sys-
tems, colorimetric recognition has become more and more popular
because it additionally offers the opportunity to develop signalling
systems for the ‘naked eye’ detection of target species.
tor based on a 1,3,5-trisubstituted-2,4,6-triethylbenzene scaffold.
The host molecule 3 contains thiourea binding sites and fluorescein
groups as signalling subunits. The chromogenic and fluorogenic
behaviour of receptor 3 was tested against certain selected anions
in organic and organic–water mixed solutions.
The synthesis of tripodal 1,3,5-trimethylamino-2,4,6-triethyl-
1
1
During the last years, a large number of receptors using groups,
benzene (2) has been published elsewere. Reaction of 2 with
such as amide, urea, thiourea,5 sulfonamide,6 pyrrole and
3
4
7
fluorescein isothiocyanate and catalytic amounts of triethylamine
8
indole, which give hydrogen bonding interactions with anions,
2 2
in refluxing CH Cl afforded receptor 3 (see Scheme 1) in moderate
1
have been reported and have been adequately coupled with differ-
ent signalling reporters. Moreover this approach is usually related
with the design and covalent link of the binding site and the signal-
ling subunit in a pre-determined fashion. Anion binding hosts may
also be designed on the basis of their flexibility or degree of pre-
organization. These concepts have been crystallized in many cases
yields as an orange solid. The H NMR spectra of tripodal receptor 3
were characterized by the presence of two signals at 1.15 and
2.95 ppm attributed to the three ethyl moieties and one singlet
at 4.67 ppm ascribable to the six methylene protons that linked
the three thiourea moieties with the benzene ring. The aromatic
signals of the three fluorescein moieties appeared in the 5.12–
8
.5 ppm interval, whereas the thiourea protons appeared at 8.1
1
2
and 8.25 ppm as broad singlets.
⇑
Corresponding authors. Tel.: +34 963877343; fax: +34 963879349.
E-mail addresses: fsanceno@upvnet.upv.es (F. Sancenón), rmaez@qim.upv.es (R.
The UV–visible response of receptor 3 in the presence of
Martínez-Máñez).
selected anions was tested in DMSO. DMSO solution of receptor
0
040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.07.039

M. E. Moragues et al. / Tetrahedron Letters 53 (2012) 5110–5113
5111
NH2
H N
2
(i)
NH2
1
2
(ii)
R
HO
R
NH
O
S
NH
NH
S
O
S
R
NH
O
R =
OH
NH
NH
3
ꢁ
5
ꢁ3
Figure 2. Colour change observed for chemosensor 3 (2.70 ꢀ 10 mol dm ) in
DMSO upon addition of: (a) 4 equiv and (b) 10 equiv of various anions as
tetrabutylammonium salts at room temperature; (c) Fluorescence emission of
DMSO solutions of receptor 3 with 10 equiv of anions when irradiating at 365 nm.
Scheme 1. Synthesis of receptor 3. Reagents and conditions: (i) (1) paraformalde-
hyde–ZnBr –HBr/AcOH–90 °C; (2) potassium phthalimide–dry DMSO–90 °C; (3)
hydrazine hydrate–EtOH/toluene (2:1) –reflux ; (ii) fluorescein isothiocyanate–
CH Cl –triethylamine–reflux.
2
1
1
2
2
ꢁ
5
ꢁ3
3.0
3
2
2
1
1
.0
.5
.0
.5
.0
3
(5.0 ꢀ 10 mol dm ) showed very weak absorption bands (cen-
2
2
.8
.6
tred at 432, 457, 486 and 528 nm) in the visible zone (see Fig. 1).
From previous studies on fluorescein derivatives,13 the absence of
colour suggested that the colourless cyclic lactone form of fluores-
cein is the predominant isomer in receptor 3 in DMSO solution.
In a further step, the UV–visible response of receptor 3 was
2.4
2
2
1
.2
.0
.8
0.5
0.0
1.6
1.4
ꢁ
3ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
0
2
4
6
8
10
tested against several anions (CN , F , Cl , Br , I , NO , H
2
PO4
,
-
3
Equiv AcO
1
.2
ꢁ
ꢁ
ꢁ
ꢁ
HSO4 , ClO4 , AcO , BzO and Cit ). The response of 3 in the pres-
1.0
0.8
0.6
ence of 1 equiv of the selected anions can be seen in Figure 1. Addi-
tion of Cl , Br , I , NO , HSO4 , ClO4 and Cit induced negligible
changes in the UV–visible profiles, whereas H PO4 and BzO pro-
2
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
3ꢁ
3
0
.4
ꢁ
ꢁ
0.2
0.0
0.2
moted a small increase in the absorbance of the visible bands.
However, the most remarkable changes were observed upon addi-
-
3
00
400
500
Wavelength (nm)
600
ꢁ
ꢁ
ꢁ
tion of CN , F and AcO for which the absorbances of the four vis-
ible bands were highly enhanced. These changes were reflected in
colour modulations from colourless to bright orange (see Fig. 2a
and b). These bands in the 400–550 nm range can be attributed
to the presence of the open form of the fluorescein dye. A remark-
able enhancement of the fluorescence was also observed
ꢁ
5
ꢁ3
Figure 3. UV–visible spectral changes of receptor 3 (5.0 ꢀ 10 mol dm ) in DMSO
ꢁ
upon addition of AcO (0.2–10 equiv). The inset shows the nonlinear curve fitting of
ꢁ
the absorbance at 520 nm against the added AcO .
(
see Fig. 2c).
ꢁ5
ꢁ3
DMSO solution (5.0 ꢀ 10 mol dm ) upon addition of increasing
Titration profiles of receptor 3 upon addition of increasing
ꢁ
quantities of AcO anion (from 0.2 to 10 equiv), as well as the non-
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
2
quantities of CN , F , H PO4 , AcO and BzO anions were carried
out. Figure 3 shows the visible spectral changes of receptor 3 in
linear curve fitting of the absorbance band centred at ca. 520 nm.
As it can be seen a clear and gradual absorbance enhancement of
the visible band was observed.
ꢁ
ꢁ
The titration profiles of receptor 3 upon addition of CN and F
-
anions induced similar absorption enhancements to those ob-
served upon addition of AcO and allowed us to fit the experimen-
CN
ꢁ
1
0
0
0
0
0
.0
.8
.6
.4
.2
.0
tal data to a two step mechanism (see also Table 1). The changes in
ꢁ
-
2
the visible zone upon addition of H PO4 and BzO anions were
ꢁ
AcO
ꢁ
less pronounced (see Fig. 4 for BzO anion and also Table 1 for
the stability constants) reflecting the lower interaction of these an-
ꢁ
ꢁ
ꢁ
-
ions with 3 when compared with CN , F and AcO . The chromo-
F
Table 1
Stability constants for the interaction of receptor 3 with some anions in DMSO
-
BzO
Log ba
Anion
Interaction
-
2
H PO4
ꢁ
OH
1:2
1:2
1:2
1:2
1:2
1:2
3.41 ± 0.01
4.79 ± 0.01
3.67 ± 0.01
3.73 ± 0.01
0.43 ± 0.01
others
ꢁ
CN
ꢁ
F
ꢁ
AcO
BzO
300
400
500
600
ꢁ
Wavelength (nm)
ꢁ
b
H
2
PO4
ND
ꢁ
5
ꢁ3
a
Figure 1. Changes in the UV–visible spectra of receptor 3 (5.0 ꢀ 10 mol dm ) in
Calculated using the programme HypSpec 1.1.18 for Eq. 3.
The spectral changes were too small to calculate binding constant.
b
DMSO after addition of 1 equiv of selected anions.

5
112
M. E. Moragues et al. / Tetrahedron Letters 53 (2012) 5110–5113
1
1
0
0
0
0
0
0
0
0
0
0
.1
.0
.9
.8
.7
.6
.5
.4
.3
.2
.1
.0
In summary, we have synthesized a new tripodal chemosensor
1
0
.0
.8
containing thiourea binding sites and fluorescein as signalling re-
porter for the colorimetric detection of basic anions in DMSO and
mixed water–DMSO solutions. The colorimetric response observed
is due to the opening of the lactone ring of fluorescein induced by
the deprotonation of the hydroxyl moieties.
0.6
0.4
0.2
0
.0
0
2
4
6
8
10
-
Equiv BzO
Acknowledgments
Financial support from the Spanish Government (project
MAT2009-14564-C04-01) and the Generalitat Valenciana (project
PROMETEO/2009/016) is gratefully acknowledged. M.E.M. thanks
the Ministerio de Educación for a Doctoral FPU Fellowship.
-
0.1
3
00
400
500
Wavelength (nm)
600
References and notes
ꢁ
5
ꢁ3
Figure 4. UV–visible spectral changes of 3 (5.0 ꢀ 10 mol dm ) in DMSO upon
ꢁ
1. (a) Schmdtchen, F. P.; Berger, M. Chem. Rev. 1997, 97, 1609–1646; (b) Beer, P.
D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40, 486–516; (c) Wenzel, M.; Hiscock,
J. R.; Gale, P. A. Chem. Soc. Rev. 2012, 41(1), 480–520; (d) Suksai, C.; Tuntulani, T.
Chem. Soc. Rev. 2003, 32, 192–202; (e) Gunnlaugsson, T.; Glynn, M.; Tocci, G.
M.; Kruger, P. E.; Pfeffer, F. M. Coord. Chem. Rev. 2006, 250, 3094–3117.
addition of BzO (0.2–10 equiv) anion. The inset shows the nonlinear curve fitting
of the absorbance at 520 nm against the added BzO .
ꢁ
2.
(a) Moragues, M. E.; Martínez-Máñez, R.; Sancenón, F. Chem. Soc. Rev. 2011, 40,
2
4
3
593–2643; (b) Martínez-Máñez, R.; Sancenón, F. Chem. Rev. 2003, 103, 4419–
476; (c) Martínez-Máñez, R.; Sancenón, F. Coord. Chem. Rev. 2006, 250, 3081–
093; (d) Wiskur, S. L.; Aït-Haddou, H.; Lavigne, J. J.; Anslyn, E. V. Acc. Chem. Res.
genic response of receptor 3 is clearly related with the basicity of
the tested anions and it was clear from the results that an increase
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
in the basicity of the anion (CN ꢂ F > AcO > BzO > H
2
PO4 was
2001, 34, 963–972; (e) Amendola, V.; Esteban-Gómez, D.; Fabbrizzi, L.; Lichelli,
M. Acc. Chem. Res. 2006, 39, 343–348.
directly reflected in a larger enhancement of the intensity of the
visible bands and also in an enhancement of the fluorescence. In
fact the same colour modulation and fluorescence enhancement
were observed upon titration of 3 in DMSO with tetrabutylammo-
nium hydroxide.
3
.
.
(a) Kang, J.; Jo, J. H.; In, S. Tetrahedron Lett. 2004, 45, 5225–5228; (b)
Chmielewski, M.; Jurczak, J. Tetrahedron Lett. 2004, 45, 6007–6010; (c)
Chmielewski, M.; Jurczak, J. Tetrahedron Lett. 2005, 46, 3085–3088; (d) Choi,
K.; Hamilton, A. D. Coord. Chem. Rev. 2003, 240, 101–110; (e) Evans, L. S.; Gale,
P. A. Chem. Commun. 2004, 1286–1287.
(a) Cho, E. J.; Ryu, B. J.; Lee, Y. J.; Nam, K. C. Org. Lett. 2005, 7, 2607–2609; (b)
Burns, D. H.; Calderon-Kawasaki, K.; Kularatne, S. J. Org. Chem. 2005, 70, 2803–
2807; (c) Bao, X. P.; Zhang, H.; Zhang, Z.; Wu, L.; Li, Z. Y. Inorg. Chem. Commun.
4
The best fitting of the titration data using the program HypSpec
was obtained when two consecutive processes were considered;
that is, the formation of 1:1 hydrogen-bonding complexes between
2
007, 10, 728–729; (d) Esteban-Gómez, D.; Fabbrizzi, L.; Licchelli, M.; Monzani,
E. Org. Biomol. Chem. 2005, 3, 1495–1500; (e) Loeb, S. J. J. Am. Chem. Soc. 2004,
26, 5030–5031.
5. (a) Kato, R.; Nishizawa, S.; Hayashita, T.; Teramae, N. Tetrahedron Lett. 2001, 42,
053–5056; (b) Kondo, S. I.; Nagamine, M.; Yano, Y. Tetrahedron Lett. 2003, 44,
3
and the corresponding anion Eq. 1 and a deprotonation reaction
1
upon addition of excess of anion Eq. 2:
5
ꢁ
ꢁ
3
3
3
þ A ¡3 ꢁ A
ð1Þ
ð2Þ
ð3Þ
8801–8804; (c) Bao, X. P.; Wang, L.; Wu, L.; Li, Z. Y. Supramol. Chem. 2008, 20,
467–478; (d) Gunnlaugsson, T.; Davis, A. P.; O’Brien, J. E.; Glynn, M. Org. Biomol.
Chem. 2005, 3, 48–56; (e) Jun, E. J.; Swamy, K. M. K.; Bang, H.; Kim, S.-J.; Yoon, J.
Tetrahedron Lett. 2006, 47, 3103–3106.
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ A þ A ¡3 þ HA
2
ꢁ
ꢁ
ꢁ
þ 2A ¡3 þ HA2
6.
(a) Starnes, S. D.; Arungundram, S.; Saunders, C. H. Tetrahedron Lett. 2002, 43,
7
785–7788; (b) Chung, Y. M.; Raman, B.; Kim, D. S.; Ahn, K. H. Chem. Commun.
From the titration profiles the stability constants for the inter-
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
2006, 186–188.
action of 3 with the anions F , CN , AcO , BzO , H
OH were calculated (see Table 1).
2
PO4 and
7.
(a) Black, C. B.; Andrioletti, B.; Try, A. C.; Ruiperez, C.; Sessler, J. L. J. Am. Chem.
Soc. 1999, 121, 10438–10439; (b) Sessler, J. L.; Maeda, H.; Mizuno, T.; Lynch, V.
M.; Furuta, H. Chem. Commun. 2002, 862–863; (c) Sessler, J. L.; Pantos, G. D.;
Katayev, E.; Lynch, V. M. Org. Lett. 2003, 5, 4141–4144; (d) Gale, P. A.; Light, M.
E.; McNally, B.; Navakhun, K.; Sliwinski, K. E.; Smith, B. D. Chem. Commun. 2005,
ꢁ
Values of stability constants for the overall process in Eq. 3 fol-
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
lowed the order CN > Ac > F > OH > BzO . Moreover it was
found that the logarithms of the stability constants for the coordi-
nation process Eq. 1 were small (that is, ꢁ9.32, ꢁ3.21, ꢁ3.32, ꢁ0.27
3
773–3775.
8. (a) Chang, K. J.; Moon, D.; Lah, M. S.; Jeong, K. S. Angew. Chem., Int. Ed. 2005, 44,
7926–7929; (b) Kim, N. K.; Chang, K. J.; Moon, D.; Lah, M. S.; Jeong, K. S. Chem.
Commun. 2007, 3401–3403; (c) Yu, J. O.; Browning, C. S.; Farrar, D. H. Chem.
Commun. 2008, 1020–1022.
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
and ꢁ2.34 for OH , CN , F , AcO and BzO , respectively). The low
ꢁ
value found for coordination with OH (and its large value ob-
served for deprotonation that is, 12.73) clearly indicated a favour-
able proton transfer reaction between 3 and OH anion whereas
9. (a) Metzger, A.; Anslyn, E. V. Angew. Chem. Int. Ed. 1998, 37, 649–652; (b)
Wiskur, S. L.; Anslyn, E. V. J. Am. Chem. Soc. 2001, 123, 10109–10110; (c) Aït-
Haddou, H.; Wiskur, S. L.; Lynch, V. M.; Anslyn, E. V. J. Am. Chem. Soc. 2001, 123,
ꢁ
the other anions formed 1:1 hydrogen-bonding complexes (most
likely with the thiourea binding sites) at low anion concentrations.
Upon addition of increasing quantities of anions a deprotonation
reaction occurs. The enhancement of the absorption and the fluo-
rescence observed in the presence of basic anions suggested that
the sensing mechanism would most likely involve the opening of
the lactone ring in the fluorescein chromophore.
11296–11297.
10. For recent works on anion chemosensors see for example: (a) Climent, E.;
Giménez, C.; Marcos, M. D.; Martínez-Máñez, R.; Sancenón, F.; Soto, J. Chem.
Commun. 2011, 47, 6873–6875; (b) Calero, P.; Hecht, M.; Martínez-Máñez, R.;
Sancenón, F.; Soto, J.; Vivancos, J. L.; Rurack, K. Chem. Commun. 2011, 47,
10599–10601; (c) Ábalos, T.; Jiménez, D.; Moragues, M.; Royo, S.; Martínez-
Máñez, R.; Sancenón, F.; Soto, J.; Costero, A. M.; Parra, M.; Gil, S. Dalton Trans.
2010, 39, 3449–3459; (d) Climent, E.; Calero, P.; Marcos, M. D.; Martínez-
Máñez, R.; Sancenón, F.; Soto, J. Chem. Eur. J. 2009, 15, 1816–1820; (e) Ábalos,
T.; Royo, S.; Martínez-Máñez, R.; Sancenón, F.; Soto, J.; Costero, A. M.; Gil, S.;
Parra, M. New J. Chem. 2009, 33, 1641–1645; (f) Comes, M.; Marcos, M. D.;
Martínez-Máñez, R.; Sancenón, F.; Soto, J.; Villaescusa, L. A.; Amorós, P. Chem.
Commun. 2008, 3639–3641.
Additional studies were also carried out with DMSO–water
ꢁ
5
ꢁ3
9
0:10 v/v solutions (pH 7.0) of receptor 3 (5.0 ꢀ 10 mol dm
)
in order to test the possible application for anion sensing in an
aqueous medium. Addition of CN , F , H PO4 , AcO and BzO an-
2
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
11.
Vacca, A.; Nativi, C.; Cacciarini, M.; Pergoli, R.; Roelens, S. J. Am. Chem. Soc.
2004, 126, 16456–16464.
ions to DMSO–water solutions of 3 resulted in same changes on the
UV–visible spectrum than the observed when using DMSO alone.
The only difference was related with the fact that more equivalents
of the anions were necessary to obtain the same change in the
absorbance. This is a clear consequence of the partial solvation of
the anion in the presence of water that reduced their basicity.
12. Synthesis of compound 2: In a first step, to a mixture of paraformaldehyde
(
(
16.7 g, 556.3 mmol) and triethylbenzene (1, 10 mL, 53.1 mmol) in HBr/AcOH
100 mL, 30 wt %) zinc bromide (19.7 g, 87.5 mmol) was slowly added at room
temperature. The mixture was heated to 90 °C for 16.5 h, during which time
white crystals were formed. The reaction was cooled to room temperature, and
the white solid was filtered off, washed with water, and dried under vacuum

M. E. Moragues et al. / Tetrahedron Letters 53 (2012) 5110–5113
5113
overnight to give 1,3,5-tris(bromomethyl)-2,4,6-triethylbenzene (22.8 g,
1.7 mmol, 97%) as white solid. In second step, to a suspension of
potassium phthalimide (8.4 g, 45.4 mmol) in dry DMSO (75 mL) 1,3,5-
tris(bromomethyl)-2,4,6-triethylbenzene (5.0 g, 11.3 mmol) was added at room
temperature, under nitrogen atmosphere. The reaction mixture was heated to
reaction mixture was refluxed for 20 h, and during this time a white solid was
formed. The reaction was cooled to room temperature, and the white solid was
filtered off, dissolved in a 40% aqueous solution of KOH (120 mL), and extracted
5
a
a
with CHCl
water (3 ꢀ 150 mL) and dried over Na
gave 2 (0.973 g, 3.90 mmol, 78%) as a white solid. Mp 138–140 °C; H NMR
3
(3 ꢀ 150 mL). The combined organic layers were washed with
2
SO . Evaporation of the organic solvent
4
1
8
4 °C for 8 h; the solution obtained was cooled to 0 °C, and the formation of a
white solid was observed. After 1 h at room temperature, the solid was filtered
off, dissolved in water (100 mL), and extracted with CH Cl
(2 ꢀ 100 mL). The
combined organic layers were washed with water (2 ꢀ 50 mL), dried over
Na SO and concentrated to give 1,3,5-tris(phthalimidomethyl)-2,4,6-
ꢁ
3
(0.1 mol dm in CDCl
1.23 (t, 9H). 13C NMR (CDCl
3
3
, 200 MHz) d: 3.87 (bs, 6H), 2.82 (q, 6H), 1.26 (bs, 6H),
2
2
, 50 MHz) d: 140.3, 137.4, 39.6, 22.5, 16.8.
Synthesis of receptor 3: A mixture of 2 (26.8 mg, 0.106 mmol) and fluorescein
isothiocyanate (125 mg, 0.32 mmol) was dissolved in dichloromethane
(20 mL). Then, triethylamine (1.5 mL, 10.7 mmol) was added and the mixture
refluxed for 24 h. After cooling to 25 °C, the solvent was removed in vacuo
giving a residue, which was purified by silica column (increasing polarity from
ethyl acetate/hexane, 10/1, v/v to ethyl acetate/hexane, 20/1, v/v) to yield
2
4
,
triethylbenzene (4.88 g, 7.63 mmol, 67%) as white crystals. Then the mother
liquor was poured into water (200 mL), and the white precipitate formed was
filtered off. The solid was dissolved in CH
3 ꢀ 50 mL), and dried over Na SO . Evaporation of the organic solvent gave a
crude (2.69 g) which was purified by flash column chromatography on silica
gel (hexane/EtOAc, 1/1, v/v) to afford second amount of 1,3,5-
2 2
Cl (100 mL), washed with water
(
2
4
receptor 3 as an orange solid (42 mg, 0.03 mmol, 28%). 1H NMR (DMSO-d
,
6
a
300 MHz) d: 10.2 (s, 6H), 8.25 (s, 3H), 8.10 (s, 3H), 7.75 (d, 3H), 7.21 (d, 3H),
tris(phthalimidomethyl)-2,4,6-triethylbenzene (1.45 g, 2.27 mmol, 20%). In the
thrid step, to a suspension of 1,3,5-tris(phthalimidomethyl)-2,4,6-triethylbenzene
7.14 (d, 3H), 6.62 (dd, 3H), 6.58 (dd, 3H), 5.24 (d, 3H), 5.12 (s, 3H), 4.67 (s, 6H),
2.95 (q, 6H), 1.15 (t, 9H). MS (FAB): m/z 1415 (M ).
+
(
3
3.2 g, 5.0 mmol) in EtOH/toluene 2:1 v/v (18 mL) hydrazine hydrate (0.98 mL,
0.8 mmol) was added at room temperature under nitrogen atmosphere. The
13. Huo, F.-J.; Yin, C.-X.; Yang, Y.-T.; Su, J.; Chao, J.-B.; Liu, D.-S. Anal. Chem. 2012,
84, 2219–2223.