Bishydrazide derivatives of isoindoline as simple anion receptors

Article abstract of DOI:10.1021/jo802288u

Isoindoline has been investigated as a scaffold for the construction of anion receptors. A family of bishydrazide derivatives of isoindoline has been synthesized, and the anion-binding properties of these receptors were investigated both in solution and in the solid state. Enhanced affinity toward halides has been observed for isoindoline-based ligands compared to analogous pyrroledicarboxyamides. However, in the case of highly basic anions, the anion binding is accompanied by partial deprotonation of the receptors, which also leads to the color changes of ligands' solutions.

Full text of DOI:10.1021/jo802288u

Bishydrazide Derivatives of Isoindoline as Simple Anion Receptors
Paweł Dydio,†,‡ Tomasz Zielin´ski,† and Janusz Jurczak*,†,‡
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland,
and Department of Chemistry, Warsaw UniVersity, Pasteura 1, 02-093 Warsaw, Poland
jurczak@icho.edu.pl
ReceiVed October 11, 2008
Isoindoline has been investigated as a scaffold for the construction of anion receptors. A family of
bishydrazide derivatives of isoindoline has been synthesized, and the anion-binding properties of these
receptors were investigated both in solution and in the solid state. Enhanced affinity toward halides has
been observed for isoindoline-based ligands compared to analogous pyrroledicarboxyamides. However,
in the case of highly basic anions, the anion binding is accompanied by partial deprotonation of the
receptors, which also leads to the color changes of ligands’ solutions.
Introduction
acid-base,4 hydrophobic,5 anion-π,6 and hydrogen bonds.7
Hydrogen bonds are most commonly used for the construction
of neutral receptors, as their accessibility, directional character,
and distance-dependent character enable assembly of binding
sites that are adjusted for specific anions, thus leading to
selective and efficient receptors.7
Among frequently used hydrogen bond donors s amides,
sulfonoamides, ureas, hydrazides, hydrazones s the pyrrole
moiety is an exceptional one. Contrary to the other groups,8
pyrrole can act only as a donor; therefore, a risk of formation
Anions are of crucial importance in a range of biological,
chemical, medical, and environmental processes.1 Due to this
fact, anion complexation is an intensively explored area of
supramolecular chemistry.2 Binding of negatively charged
species can be achieved by utilization of electrostatic attraction3
or by weaker, but more directional, interactions - Lewis
* Fax: (+48) 22-632-66-81.
† Polish Academy of Sciences.
‡ Warsaw University.
(4) Katz, H. E. J. Am. Chem. Soc. 1985, 107, 1420–1421. Katz, H. E. J.
Org. Chem. 1985, 50, 5027–5032.
(5) Inoue, Y.; Hakushi, T.; Liu, Y.; Tong, L.-H.; Shen, B.-J.; Jin, D.-S. J. Am.
Chem. Soc. 1993, 115, 475–481. Steed, J. W.; Juneja, R. K.; Atwood, J. L. Angew.
Chem., Int. Ed. 1994, 33, 2456–2457.
(6) Schottel, B. L.; Chifotides, H. T.; Dunbar, K. R. Chem. Soc. ReV. 2008,
37, 68–83. Mascal, M.; Yakovlev, I.; Nikitin, E. B.; Fettinger, J. C. Angew.
Chem., Int. Ed. 2007, 46, 8782–8784.
(7) Kang, S. O.; Hossain, M. A.; Bowman-James, K. Coord. Chem. ReV.
2006, 250, 3038–3052. Kang, S. O.; Begum, R. A.; Bowman-James, K. Angew.
Chem., Int. Ed. 2006, 45, 7882–7894. Gale, P. A. Acc. Chem. Res. 2006, 39,
465–475. Bondy, C. R.; Loeb, S. J. Coord. Chem. ReV. 2003, 240, 77–99.
(1) Sessler, J. L.; Gale, P. A.; Cho, W. S. Anion Receptor Chemistry; The
Royal Society of Chemistry: Cambridge, U.K., 2006.
(2) Gale, P. A.; Garcia-Garrido, S. E.; Garric, J. Chem. Soc. ReV. 2008, 37,
151–190. Katayev, E. A.; Ustynyuk, Sessler, J. L. Coord. Chem. ReV. 2006,
250, 3004–3037. Gale, P. A.; Quesada, R. Coord. Chem. ReV. 2006, 250, 3219–
3244. Bowman-James, K. Acc. Chem. Res. 2005, 38, 671–678. Gale, P. A. Coord.
Chem. ReV. 2003, 240, 191–221. Gale, P. A. Coord. Chem. ReV. 2001, 213,
79–128. Beer, P. D.; Gale, P. A. Angew. Chem., Int. Ed. 2001, 40, 486–516.
(3) Worm, K.; Schmidtchen, F. P.; Schier, A.; Scha¨fer, A.; Hesse, M. Angew.
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1977, 16, 720–722.
10.1021/jo802288u CCC: $40.75
Published on Web 01/27/2009
2009 American Chemical Society
J. Org. Chem. 2009, 74, 1525–1530 1525

Dydio et al.
SCHEME 1. Synthesis of Ligands 2
of unfavorable intermolecular hydrogen bonds is diminished.
Due to this feature, the pyrrole ring has been extensively used
for the construction of anion receptors.9
esters,12 and commercially available 1,3-diiminoisoindoline
(Scheme 1) in satisfactory overall yields (50-87%).
Having prepared the model ligands, we started to determine
their anion-binding properties. As mentioned above, due to the
optical properties of the built-in isoindoline chromophore, we
hoped that our systems could signal the presence of specific
anionic guests by changes of color. It turned out that interactions
with anions, even in a competitive medium such as DMSO,
can be confirmed by simple naked-eye observation of the
solutions of these receptors (Figure 1). In some cases, this
observation allows to distinguish between the types of anions
used. For all ligands 2a-2d, the most spectacular color changes
were detected for highly basic anions (i.e., fluoride). Having
observed such effects, we carried out the UV/vis titration
experiments to determine quantitatively the receptors’ affinities
toward anions.
Incorporation of two additional amide sidearms to the pyrrole
ring leads to the important building block 1, with the enhanced
affinity toward anions, as reported by Gale and co-workers.10
Inspired by this structural motif, we decided to study a novel
building block 2 that offers a similar binding cleft but is
equipped with more acidic NHs, so enhanced anion binding may
be expected. Moreover, the isoindoline moiety is well-known
as a building block for high-performance pigments.11 Thus the
ligands of type 2 represent an attractive combination of an
anchoring site with a signaling subunit and potentially can be
used for preparation of optical sensors for anions. In this
communication, we will present our studies on simple bishy-
drazides derived from 1,3-diiminoisoindoline as a building block
for anion receptors.
The changes in the UV/vis spectra allowed us to calculate
the values of the binding constants (Table 1), and all the data
gave a satisfactory fit with the 1:1 model for all anions.
However, careful examination of the UV spectra during the
titrations revealed that no clear isosbestic point could be
-
observed upon addition of H2PO4 to the solutions of ligands
2a, 2b, and 2d (Figure S2, Supporting Information), which
suggested that other processes occurred than simple 1:1 binding.
Thus, we also fitted experimental data using a 1:2 model, and
indeed, we obtained a better fit for the interaction of ligands
Results and Discussion
-
2a, 2b, and 2d with H2PO4 (see Figure S1). Interestingly,
titration of ligand 2c with H2PO4- gave an isosbestic point, and
the data were best fitted to the 1:1 model. The stoichiometry of
the complexes was also examined using Job plots analysis,
showing 1:1 binding mode even in the case of H2PO4- (Figure
S4), which confirms predomination of the 1:1 complexes in the
range of concentrations used during the experiments (see the
species distribution diagram, Figure S3). The observed selectiv-
ity of receptors 2 toward anions followed a common trend of
In order to perform extensive studies of anion-binding
properties of the type 2 ligands, we decided to vary significantly
the side groups, R, and obtained the derivatives of various acids:
caproic, benzoic, picolinic, and 2-pyrrolecarboxylic acid. Ali-
phatic derivative, 2a, should have the least acidic NH protons,
thus being the weakest binder in the series. 2b and 2c represent
common aromatic scaffolds, whereas 2d possesses two ad-
ditional anchoring points and its enhanced affinity toward anions
can be expected.
oxoanions over halides: AcO- > PhCOO- > H2PO4 . Cl-,
-
with unusual preference for carboxylates over phosphate.
In view of the fact that the optical response was more
pronounced for more basic anions, it is likely that the color
changes on which we based our calculations were mainly an
effect of ligand deprotonation, rather than the anion complexa-
tion.13,14 To check this hypothesis, we performed experiments
The first advantage of our systems is a short and simple
synthesis, which is a great asset to the future introduction of
this building block into more sophisticated systems. All ligands
(2a-2d) were synthesized in two steps from easily obtainable
(8) Imidazolium group also acts only as a hydrogen bond donor; however,
it is positively charged and forms electrostatic interactions with anions. Thus,
we excluded the group from the list. For the review on imidazolium-based
receptors see: Yoon, J.; Kim, S. K.; Singhb, N. J.; Kim, K. S. Chem. Soc. ReV.
2006, 35, 355–360.
(9) Sessler, J. L.; Seidel, D. Angew. Chem., Int. Ed. 2003, 42, 5134–5175.
Sessler, J. L.; Camiolo, S.; Gale, P. A. Coord. Chem. ReV. 2003, 240, 17–55.
Gale, P. A.; Anzenbacher, P., Jr.; Sessler, J. L. Coord. Chem. ReV. 2001, 222,
57–102.
(12) 3a-3c are commercially available, 3d was obtained according to: Barker,
P.; Gendler, P.; Rapoport, H. J. Org. Chem. 1978, 43, 4849–4855.
(13) Gunnlaugsson, T.; Kruger, P. E.; Jensen, P.; Pfeffer, F. M.; Hussey,
G. M. Tetrahedron Lett. 2003, 44, 8909–8913. Gunnlaugsson, T.; Glynn, M.;
Tocci (ne´e Hussey), G. M.; Kruger, P. E.; Pfeffer, F. M. Coord. Chem. ReV.
2006, 250, 3094–3117.
(10) Gale, P. A.; Camiolo, S.; Tizzard, G. J.; Chapman, C. P.; Light, M. E.;
Coles, S. J.; Hursthouse, M. B. J. Org. Chem. 2001, 66, 7849–7853.
(11) Herbst, W.; Hunger, K. Industrial Organic Pigments: Production,
Properties, Applications, 3rd ed.; Wiley-VCH: Weinheim, Germany, 2004. Smith,
H. M. High Performance Pigments; Wiley-VCH: Weinheim, Germany, 2003.
(14) Amendola, V.; Esteban-Gomez, D.; Fabbrizzi, L.; Licchelli, M. Acc.
Chem. Res. 2006, 39, 343–353. Esteban-Gomez, D.; Fabbrizzi, L.; Liechelli,
M. J. Org. Chem. 2005, 70, 5717–5720. Boiocchi, M.; Del Boca, L.; Esteban-
Gomez, D.; Fabbrizzi, L.; Licchelli, M.; Monzani, E. Chem.-Eur. J. 2005, 11,
3097–3104.
1526 J. Org. Chem. Vol. 74, No. 4, 2009

Bishydrazide DeriVatiVes of Isoindoline
FIGURE 1. Changes of color of ligands 2a-2d in DMSO (C ) 4 x 10-4 M) in the presence of 3 equiv of anions as TBA salts.
TABLE 1. Binding Constants (log Ka) for the Formation of 1:1
Complexes of Model Ligands with Various Anions in DMSO +
0.5% H2O at 298 Ka
complex formation reversible on the NMR time scale. For the
chloride and bromide anions, we observed sharp proton signals
over the whole titration and performed data fitting for the 1:1
model (see Figures S8 and 3). Thus, the deprotonation by less
basic anions was excluded, again. Moreover, the binding
constant values from both titration techniques were in satisfying
agreement for the weak basic anions; therefore, the anion
binding was the sole process in the solution. The values of the
binding constants are given in Table 2.
anions
2a
2b
2c
2d
Cl-
<2.6b
4.4
5.7
3.8
4.3
<2.6b
4.5
5.9
4.1
4.6
<2.6b
>6
<3b
4.3
5.3
3.8
4.6
8.3
PhCOO-
AcO-
>7
-
H2PO4-
5.2
c
c
H2PO4 log ꢀ1
-
H2PO4 log ꢀ2
7.2
8.4
We also made the 1H NMR titration experiments with more
a Determined by UV/vis titration. Errors estimated to be <15%. TBA
salts were used as a source of anions. b Interaction too weak to be
precisely measured. c Values of binding constants (logꢀ1 and logꢀ2) for
the formation 1:2 complexes (ligand:anion).
-
basic anions (i.e., PhCOO- and H2PO4 ). It turned out that upon
addition of TBA salts, the signal of hydrazide-NH resonance
broadened and eventually disappeared in the baseline (after
addition of about 2.5 equiv of anions). For the isoindoline-
NH, the same effect was triggered by the addition of the very
first portion of anions (ca. 0.2 equiv). Thus, the deprotonation
by highly acidic anions was confirmed. Fitting the changes in
the chemical shift of the hydrazide-NH resonance to 1:1
isotherm led to values equal to about 5000 and 2000 [M-1] for
similar to those reported by Fabbrizzi14 and compared UV/vis
spectra of ligands upon addition of TBA salts and TBA
hydroxide.
The trends of spectral changes induced by increasing con-
centration of highly basic anions (e.g., PhCOO-) and hydroxide
anions are quite similar (Figure 2), so the assumption of
deprotonation was partially proven, especially by the develop-
ment of a new band in the region of 390-445 nm. Nevertheless,
there were no such observations for less basic anions (e.g., Cl-;
Figure 2), thus we assumed that in these cases complexation
was not accompanied by deprotonation of the receptor. How-
ever, the binding constants for those anions were too low to be
precisely determined by UV/vis technique. They can be roughly
estimated between 100 and 1000 [M-1].
-
receptor 2b with PhCOO- and H2PO4 , respectively (see Figure
S7). A comparison of these findings with the UV/vis results
(ca. 3 x 104 and 4 x 104 [M-1] for PhCOO- and H2PO4
,
-
respectively) demonstrates the influence of ligand concentration
on the estimated values of the binding constant and confirms
the hypothesis of ligand deprotonation.
The differences of the binding constants calculated on the
basis of the UV/vis and 1H NMR experiments could also arise
from the intermolecular interactions, which are more pronounced
in more concentrated solutions. In order to verify this hypothesis,
we performed dilution experiments. We verified that compounds
2 obey the Lambert-Beer law (Figure S5), as well that the 1H
NMR spectra of ligands 2 do not change upon dilution. Thus,
we excluded the possibility of self-aggregation of ligands within
the wide range of concentration from about 10-6 to 10-1 M.
In the case of the ligands possessing an acidic hydrogen bond
donor, like receptors 2a-2d, anion recognition is often ac-
companied by a significant degree of deprotonation.15 This
process is favorable in highly diluted receptor solutions since
the ratio of hydrogen-bonded and deprotonated forms of ligands
is proportional to the total receptor concentration. Therefore,
the UV/vis titration technique is much more sensitive to the
accompanying process of deprotonation than the 1H NMR
technique, for which operating concentration is higher by more
than 2 orders of magnitude. Thus, the UV/vis determined
binding constants may be more distorted and; consequently,
there would be no agreement between the values obtained from
both these techniques.
1
We could not use H NMR technique for the ligand 2c due
to its low solubility in DMSO. However, it solubilized readily
after addition of TBA-chloride, proving its interaction with
anions.
Furthermore, we encountered a more intriguing problem with
compound 2a that exists in three rotameric forms in the DMSO
solution. They were observable by the NMR spectroscopy at
room temperature (Figure S9a). Elevation of the temperature
to 343 K led to a rotation reversible on the NMR time scale
and the signals coalesced (Figure S9b). We managed to monitor,
independently, the changes of chemical shifts upon addition of
TBA-chloride for all three rotamers (Figure 3). We fit the data
to a 1:1 model,16 obtaining three values (about 1000, 100, and
50 [M-1]) assigned to three rotameric forms of ligand 2a. Similar
Therefore, we decided to use 1H NMR titration technique as
a parallel method of determining the binding constants for the
1
anion complexes. In the course of H NMR experiments in
DMSO-d6 + 0.5% H2O (v/v), we monitored the downfield shifts
of hydrazide-NH and isoindoline-NH signals that indicated
(15) Pe´rez-Casas, C.; Yatsimirsky, A. K. J. Org. Chem. 2008, 73, 2275–
2284.
J. Org. Chem. Vol. 74, No. 4, 2009 1527

Dydio et al.
FIGURE 2. UV/vis spectra in DMSO + 0.5% H2O of free ligand and after addition 3 equiv of anions: (a) ligand 2a, (b) ligand 2b, (c) ligand 2c,
and d) ligand 2d.
TABLE 2. Binding Constants [M-1] for the Formation of 1:1
Complexes of Model Ligands with Cl- and Br- Anions in DMSO-d6
+ 0.5% H2O at 298 Ka
anions
Cl-
2ab
2bc
2cd
2dc
1000
100
50
140
110
500
200
-
Br-
50
<2
<2
e
-
-
-
e
a Determined by 1H NMR titration. Errors estimated to be <10%.
TBA salts were used as a source of anions. b The values for three
rotamers (see text for details). c The values for isoindoline-NH and
hydrazide-NH signals, respectively. d Poorly soluble in DMSO.
e Interaction too weak to be measured.
FIGURE 3. 1H NMR titration curves for NH protons in compound 2a
upon addition of TBA-Cl. Black, red, and green colors indicate curves
for which Ka values are about 1000, 100, and 50, respectively.
The determined binding constants for the ligands 2a-2d are
collected in Table 2. Anion binding of the new isoindoline
receptors 2a-2d compares favorably with that of ligands of
type 1. The values of the binding constants for complexes of
the new ligands 2a-2d are over ten times larger than for the
parent receptors (for the receptors of type 1, the values are <11
[M-1] for Cl-, and not measurable at all for Br-).10,17 Introduc-
tion of two additional anchoring points into 2d results in doubled
binding constants compared with that of 2b. Such a result shows
that, in this case, the strong preference of anti conformation of
pyrrolecarboxamides17,18 is overcome by the formation of a
hydrogen bond between pyrrolic-NH and the anion.
observation was made during titration experiments with
TBA-bromide. In this case, we succeeded in fitting a 1:1
isotherm for one rotamer only, while the rest interacted with
the bromide anion too weakly. The binding constant was
established to be about 50 [M-1] and was attributed to the best
pre-organized rotamer of receptor 2a. We cannot rationalize why
such rotamers were observed only for the ligand 2a and not for
all remaining hydrazides 2b-2d.
(16) We assumed that the ratio of distinct forms of a complex is equal to
that of free forms of ligand s the more similar values of the binding constants,
the more appropriate the assumption.
(17) Zielin´ski, T.; Jurczak, J. Tetrahedron 2005, 61, 4081–4089.
(18) Zielin´ski, T.; Dydio, P.; Jurczak, J. Tetrahedron 2008, 64, 568–574.
1528 J. Org. Chem. Vol. 74, No. 4, 2009

Bishydrazide DeriVatiVes of Isoindoline
FIGURE 4. Different views (top, bottom) of crystal structure of two forms (left, right) of the ligand 2a·H2O (the pentyl groups are omitted for
clarity).
(the N-O and O-O distances are about 2.85 Å). The second
hydrazide group is deviated from the plane (the torsion angles
are 35°) and forms hydrogen bonds with equivalent groups of
next ligand molecules (the N-O distances are about 2.8 Å).
We also succeeded in preparing a diffraction-grade single
crystal of the complex of ligand 2b with tetrabutylammonium
benzoate (TBA-PhCOO). This structure undoubtedly confirms
the process of anion complexation that takes place beside
deprotonation of the receptor in the solution. The ligand adopts
almost a symmetrical conformation with its side arms twisted
in such a manner that the hydrazide-NHs point below the ring
plane (Figure 6). The benzoate anion lies under the plane of
the isoindoline moiety and is positioned asymmetrically. One
of the oxygen atoms is located near the center of binding cleft,
almost in the mean plane, accepting a pair of strong hydrogen
bonds from both the central and one arm NHs (the N-O
distances are 2.75 and 2.96 Å, respectively). The second oxygen
atom is significantly deviated from the plane, is tilted toward
the other arm, and is bound also by two hydrogen bonds (the
N-O distances are 2.89 and 3.28 Å, respectively).
This complex structure may suggest that the cleft is still
slightly too small for the carboxylate anion. In the crystal
structure, the hydrazide ligand, 2b, binds benzoate with four
hydrogen bonds, while the parent receptor 1, reported by Gale,20
is able to create only three hydrogen bonds (in the range of
2.77-2.86 Å), but the manner of positioning of the benzoate
anion remains very similar. One of the oxygen atoms is again
located almost in the center of binding cleft, in the pyrrole plane,
accepting a pair of hydrogen bonds from the pyrrole and
amide-NHs. The second oxygen atom is deviated from the
plane and is tilted toward the other amide-NH accommodating
a third hydrogen bond. Moreover, the phenyl ring is twisted
and deviated from the main plane in the same fashion in both
complex structures.
FIGURE 5. Crystal structure of 2a showing water molecules engaged
in hydrogen bonds (the pentyl groups are omitted for clarity).
Although we observed that increasing the acidity of hydrogen
bond donors of ligands 2 compared to 1 can increase affinity
toward anions (i.e., Cl-). It can also lead to deprotonation of
ligands and change the complexation phenomena into an
acid-base reaction. Such behavior was reported previously,19
and it seemed to hamper further increasing the receptors
efficiency by tuning their electronic properties.
For the purpose of the structural analysis, we obtained a
diffraction-grade single crystal of the ligand 2a by slow diffusion
of water into its solution in DMSO. The independent part
consists of two pairs of ligand and water molecules, the
structures of which are similar, and both of them have disorder
in their pentyl side chains (Figure S10). Both ligands adopt
conformations in which NH groups point almost convergently
to the binding cleft (Figure 4). Two of them, the hydrazide and
the isoindoline-NHs, are engaged in the binding of water
molecules (the N-O distances are about 2.9 Å), which are
positioned in such a manner that the oxygen is in the isoindoline
plane and the hydrogens are almost perpendicular to the ring
(Figure 5). These hydrogen atoms form hydrogen bonds with
the carbonyl group and the imine group of adjoining ligands
We could not directly compare our ligands with another,
simple and efficient pyrrole-based system as published by
(19) Camiolo, S.; Gale, P. A.; Hursthouse, M. B.; Light, M. E.; Shi, A. J.
Chem. Commun. 2002, 758–759.
(20) Camiolo, S.; Gale, P. A.; Hursthouse, M. B.; Light, M. E. Tetrahedron
Lett. 2002, 43, 6995–6996.
J. Org. Chem. Vol. 74, No. 4, 2009 1529

Dydio et al.
FIGURE 6. Different views of the X-ray crystal structure of the benzoate complex of ligand 2b (the countercation is omitted for clarity).
Maeda,21 due to the lack of appropriate crystal structures.
However, DFT calculations show that Maeda’s dipyrrolyldike-
tone also binds oxoanions with four hydrogen bonds, but the
complex has a completely flat structure. At the same time, unlike
the hydrate of ligand 2a, Maeda’s receptor, even upon com-
plexation of chloride anion, does not form a convergent binding
site in the solid state.
It is worth emphasizing that the geometry of the anchoring
site in the complex of 2b with benzoate is almost the same as
that in the free ligand 2a. The distance between nitrogen atoms
N1-N5 is 5.29 Å and the cleft angle N1-N3-N5 is 142 ° in
the anion complex, whereas, in case of the free receptor
(fragment b), the distance is 5.20 Å and the angle is about 140°.
Measurement of the geometric parameters of the binding cleft
(the distance between hydrazide donor NHs and the angle
N-N-N as described in ref. 22) shows that the binding site of
2 has novel structural properties and can be classified between
derivatives of the pyrrole-2,5-dicarboxylic acid and the azulene-
1,3-dicarboxylic acid.22
Hexanoic Acid Hydrazide 4a. The above general procedure was
followed using hexanoic acid and methyl ester (3.0 g, 23 mmol).
The reaction mixture was extracted with ethyl acetate, the extracts
were dried over MgSO4, and the solvent was removed in Vacuo.
The solid residue was purified by flash chromatography over silica
gel using ethyl acetate and MeOH [95:5] as eluents. The product
was recrystallized from hot ethyl acetate yielding 2.8 g (93%) of
the hydrazide 4a as colorless crystals, mp 64-67 °C.
1H NMR (200 MHz, DMSO) δ ) 8.90 (bs, 1H, NH), 4.13 (s, 2H,
NH2), 1.99 (t, 2H, J1 ) 7.4 Hz), 1.48 (p, 2H, J1 ) 7.4 Hz), 1.23
(m, 4H), 0.85 (t, 3H, J1 ) 6.7 Hz); 13C NMR (50 MHz, DMSO) δ
) 172.1, 33.9, 31.4, 25.4, 22.3, 14.3; HR EI calcd for C6H14N2O-
M+ 130.11061, found 130.11093; Anal. calcd for C6H14N2O C
55.35, H 10.84, N 21.52, found C 55.32, H 10.93, N 21.38.
Hydrazides 4b-4d. Detailed procedures and characterizations
are described in Supporting Information.
General Procedure for Preparation of the Ligands 2a-2d.
In a 100 mL round-bottomed flask equipped with a magnetic stirrer,
under an argon atmosphere, 1,3-diiminoisoindoline (435 mg, 2.5
mmol) and the appropriate hydrazide (7.5 mmol) were dissolved
in EtOH (30 mL). The mixture was then refluxed over a week.
1,3-Bis(hexanoyl-hydrazone)isoindoline 2a. The above general
procedure was followed using the hydrazide 4a (1.0 g). The created
suspension was filtered and washed with Et2O, and the crude
product was recrystallized from hot 1,2-dichloroethane (after cooling
down to room temperature, it was placed in a refrigerator). Yield
0.50 g (54%) of the ligand 2a as yellow crystals, mp 193-195 °C.
1H NMR (500 MHz, DMSO) δ ) 10. 07 (bm, 3H, CONH +
NH), 7.77 (m, 2H), 7.60 (t, 2H, J1 ) 1.6 Hz), 2.64 (q, 2H, J1 ) 4.2
Hz), 2.25 (m, 2H), 1.61 (m, 4H), 1.33 (m, 8H), 0.88 (m, 6H); 13C
NMR (50 MHz, DMSO) δ ) 174.5, 174.2, 168.6, 168.4, 145.9,
144.4, 140.1, 139.4, 132.9, 132.5, 130.9, 130.6, 121.4, 120.8, 34.2,
31.5, 31.0, 24.8, 23.8, 21.9, 13.9; HR ESI calcd for C20H29N5O2Na-
M+ 394.22135, found 394.21965; Anal. calcd for C20H29N5O2 C
64.67, H 7.87, N 18.85, found C 64.47, H 7.95, N 18.95.
Ligands 2b-2d. Detailed procedures and characterizations are
described in Supporting Information.
Conclusions
We investigated the anion-binding properties of the new
derivatives of isoindoline both in the solution and the solid state.
Due to the higher acidicity of the donors groups, receptors 2
bound halides more strongly than their parent compounds,
pyrroledicarboxamides 1. Unfortunately, in case of more basic
anions, the complexation process was accompanied by the partial
deprotonation of the ligands. This process triggered spectacular
color changes of the receptor’s solution. However, in the solid
state, we observed solely the anion binding with no ligand
deprotonation. Structural analysis showed that 2 has a geometry
of its binding site different from other bidentate building blocks,
thus 2 extends the pool of available structural subunits for the
design of anion receptors.
Acknowledgment. The x-ray measurements were undertaken
in the Crystallographic Unit of the Physical Chemistry Labora-
tory in the Chemistry Department of the University of Warsaw.
Experimental Section
General Procedure for Preparation of the Hydrazides
4a-d. To a 25 mL round-bottomed flask equipped with a magnetic
stirrer, N2H4 ·H2O (80% in water, 12 mL) and an appropriate ester
(3 g) were added. Then the temperature of the mixture was elevated
to 70 °C for 45 min and the mixture was cooled to room
temperature.
Supporting Information Available: General remarks, all
experimental procedures and characterization data for com-
pounds 2a-2d and 4a-4d, ORTEP plots, 1H, 13C NMR spectra,
details concerning the determination of binding constants,
titration curves, changes of UV/vis spectra, and Job plots;
crystallographic data, also in CIF format. This material is
available free of charge via the Internet at http://pubs.acs.org.
(21) Fujimoto, C.; Kusunose, Y.; Maeda, H. J. Org. Chem. 2006, 71, 2389–
2394. Maeda, H.; Ito, Y. Inorg. Chem. 2006, 45, 8205–8210.
(22) Zielin´ski, T.; Kedziorek, M.; Jurczak, J. Chem.-Eur. J. 2008, 14, 838–
846. Zielin´ski, T.; Kedziorek, M.; Jurczak, J. Tetrahedron 2005, 46, 6231–6234.
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