Binding of group 15 and group 16 oxides by a concave host containing an isophthalamide unit

Article abstract of DOI:10.3762/bjoc.8.2

A bi-macrocycle with an incorporated isophthalamide substructure was synthesized by double amide formation between an isophthaloyl dichloride and two equivalents of a bis(alkenyloxy)aniline, followed by ring-closing metathesis and hydrogenation. In contra

Full text of DOI:10.3762/bjoc.8.2

Binding of group 15 and group 16 oxides
by a concave host containing an isophthalamide unit
Jens Eckelmann, Vittorio Saggiomo, Svenja Fischmann and Ulrich Lüning*
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2012, 8, 11–17.
Otto-Diels-Institut für Organische Chemie,
Christian-Albrechts-Universität zu Kiel, Olshausenstr. 40, D-24098
Kiel, Germany
doi:10.3762/bjoc.8.2
Received: 13 September 2011
Accepted: 29 November 2011
Published: 03 January 2012
Email:
Ulrich Lüning* - luening@oc.uni-kiel.de
This article is part of the Thematic Series "Supramolecular chemistry II".
Guest Editor: C. A. Schalley
* Corresponding author
Keywords:
anion binding; association constant; estimation of binding constants;
macrocycle; molecular recognition
© 2012 Eckelmann et al; licensee Beilstein-Institut.
License and terms: see end of document.
Abstract
A bi-macrocycle with an incorporated isophthalamide substructure was synthesized by double amide formation between an iso-
phthaloyl dichloride and two equivalents of a bis(alkenyloxy)aniline, followed by ring-closing metathesis and hydrogenation. In
contrast to many related isophthalamides, the concave host exhibits a better binding for oxides, such as DMSO or pyridine-N-oxide,
than for halide anions. A general method for a quick estimation of the strength of binding derived from only a few data points is
presented and gives an estimated Kass of pyridine-N-oxide of ca. 40 M−1, NMR titration confirms 25 M−1.
Introduction
In the last decade, isophthalamide derivatives have become syn conformation can be stabilized by using isophthalamide
attractive neutral hosts as anion receptors [1,2]. Some of these derivatives capable of intramolecular hydrogen bonding to the
derivatives show a high selectivity for one anion over others CO part of the amide groups [10,11], or by other means of
[3]. Isophthalamide units have also been incorporated into bridging [12]. Due to the preorganization of such molecules, the
macrocycles [4,5] or bi-macrocycles for ion-pair and ion-triplet binding constant for chloride is impressively increased with
recognition [6-9]. During the last few years, it was also shown respect to the non-preorganized isophthalamides. However, an
that the orientation of the amide bonds of the isophthalamides intramolecular hydrogen bond can be easily broken in polar
plays an important role in the effectiveness of anion binding and solvents, hence destroying the preorganization and thus
subsequently in applications such as transmembrane anion decreasing the binding affinities for the anions. Herein we
transport. Rotation along the amide–aryl bonds leads to syn/ describe the facile synthesis and the binding properties of a
anti, syn/syn and anti/anti conformers (syn and anti defined concave host 1 with a different type of preorganization. This
with respect to the relative orientation of the NH atoms), and contains an isophthalamide unit in a bi-macrocyclic structure
only the syn/syn conformer of an isophthalamide is capable of (Figure 1). Concave hosts and especially concave reagents are
simultaneously binding an anion by both NH groups. The syn/ best envisioned as having the form of a lamp in a lampshade in
11

Beilstein J. Org. Chem. 2012, 8, 11–17.
which the light bulb is the reactive centre [13-15]. The preorga-
nization and the exact shape of the “lampshade” determine the
selectivity and the difference in binding of various guests.
Figure 1: Bi-macrocyclic concave host 1 and its non-macrocyclic
model 2.
Scheme 1: Synthetic scheme for the syntheses of concave host 1 and
non-macrocyclic derivative 2. a) Et3N, THF, 16 h, room temp., 61%; b)
Grubbs 1st gen. cat., CH2Cl2, 24 h, room temp.; c) Pd/C, H2, MeOH,
24 h, room temp., 77%; d) Et3N, THF, 18 h, room temp., 97%.
Results and Discussion
Synthesis
Besides the desired bi-macrocycle 1, isophthalamide 2 was
synthesized in order to compare the binding properties of a non-
macrocyclic host with the concave host 1. The syntheses of the there was only one cross peak of an aromatic proton of the iso-
concave host 1 and its analogue 2 are depicted in Scheme 1.
phthalamide of bi-macrocycle 1 with the NH protons: The
endo-proton in the 2-position of the isophthalic unit is in close
The preparation of concave host 1 starts with aniline 4, which proximity to the NH protons. Thus, the binding region of 1 is
was synthesized as previously published [16]. The reaction of preorganized (for details see Supporting Information File 1).
two equivalents of this aniline 4 with isophthaloyl dichloride 3
gave the open diamide 5. This tetraalkene 5 was then converted NMR binding studies
to bi-macrocycle 1 by ring-closing metathesis followed by Each of the isophthalamides, 1 and 2, was dissolved in CD2Cl2
catalytic hydrogenation. Model compound 2 was obtained by and 1H NMR spectra were recorded after addition of five
reacting isophthaloyl dichloride 3 with 2,6-dimethoxyaniline equivalents of different tetrabutylammonium halide salts
(6). The two products 1 and 2 were isolated and characterized. (TBAHal). The chemically induced shifts (CIS) of the NH and
The preorganization of the binding region was investigated by the isophthalamide endo-CH protons (i.e., the 2-position of the
NOESY experiments. While two cross peaks between the NH aromatic ring) were analyzed (Figure 2). Further addition of
protons and both types of protons in the central aromatic region guests led to larger CIS, but no saturation was observed. The
were observed in the case of the more flexible compound 2, shallow curvature and absence of saturation suggest small
Figure 2: Expansion of a part of the 1H NMR spectra (200 MHz, 298 K) of pure 1 and 2 in CD2Cl2 (bottom) and after addition of TBACl, DMSO, pyri-
dine-N-oxide (PyNO), triphenylphosphine oxide (TPPO), from bottom to top, respectively. NH proton (red circles), endo-CH proton (red squares).
12

Beilstein J. Org. Chem. 2012, 8, 11–17.
binding constants. The different magnitudes of the CIS suggest would be sufficient if a quick screening of the binding poten-
that concave host 1 binds halides with lower affinity than its tials of the hosts were possible and host–guest pairs with
acyclic relative 2, although the magnitude of the CIS need not significant association constants were identified. Estimation
be correlated with the binding constants.
rather than an exact determination of Kass would be fair enough.
Once a good candidate is recognized, a standard determination
However, when sulfoxides were added as neutral guests, the of the association constant, for example, by NMR titration, can
relative binding of these guests by 1 and 2 showed drastic be done.
differences. Dimethyl sulfoxide (DMSO), methylphenyl
sulfoxide (MPSO) and diphenyl sulfoxides (DPSO) induced a With Δδmax unknown, the magnitude of the CIS cannot distin-
shift of the endo-CH in the concave host 1 of 0.24 ppm, guish between weak and strong binding. However, when NMR
0.20 ppm and 0.25 ppm, respectively (for DMSO see Figure 2, titrations of different host–guest pairs are carried out with iden-
left, see also Supporting Information File 1), while the addition tical concentrations, small and large association constants can
of these guests had almost no effect on the endo-CH of model be differentiated by the different curvatures of the titration
compound 2 (for DMSO see Figure 2, right). Although there is graphs. In a titration curve of strong binding, the curvature is
almost no CIS observed for the endo-CH of model compound 2, more extreme, and the final value of Δδmax is approached faster
a small shift for the NH protons is observed. However, for than in the case of weak binding. Beyond 1:1 stoichiometry, the
DMSO, the CIS of the NH is larger for the concave host 1 than CIS values converge more the stronger the binding is.
for model compound 2 (0.57 ppm for 1 and 0.25 ppm for 2), in
contrast to the results of the anion-binding experiments (see Can this be a method for the quick estimation of binding
above). To the best of our knowledge, this is the second host constants? We have tested this alternative for hosts 1 and 2. All
capable of binding DMSO in an organic solvent [17]. In this measured 1H NMR shifts were normalized to a CIS at high
regard, concave host 1 seems to be selective and a better binder guest concentration, but not at saturation: The CIS from all
for negatively polarized oxygen atoms when compared to experiments that used ca. 20 equivalents of a given guest were
acyclic compound 2.
arbitrarily defined as 100%, and the CIS measured for ca. 5
equivalents of the same guest were divided by that CIS value
Next, element oxides other than sulfoxides were chosen as measured with 20 equivalents. The resulting normalized CIS
guests, namely pyridine-N-oxide (PyNO) [18,19] and triph- were plotted against the guest equivalents (Figure 3). With a
enylphosphine oxide (TPPO). PyNO showed the same behav- more strongly binding guest, the titration curve possesses a
iour as DMSO, i.e., large CIS for concave host 1, and small CIS
for the linear compound (Figure 2, PyNO, endo-CH, 0.34 ppm
for 1 and 0.14 ppm for 2). In contrast, with TPPO as guest,
model compound 2 showed a larger CIS when compared to
concave host 1 (Figure 2, TPPO). This may be explained by the
large steric bulk of TPPO, which may be too extreme to allow
TPPO to fit nicely inside the cavity of concave host 1 but still
allows a binding to the sterically less demanding non-macro-
cyclic host 2.
In order to reliably determine small binding constants, a titra-
tion up to a large excess of guest has to be carried out but, even
then, a limiting value for the CIS often is not reached and thus a
second parameter besides Kass, namely the maximum of the
observed CIS Δδmax, has to be obtained by curve fitting, which
adds to the overall error. In our host–guest systems, saturation
was not reached even when 20 equivalents of guests were used.
An even larger excess of guest changed the polarity of the
Figure 3: Normalized 1H NMR CIS (see text) for concave host 1 with
solvent to such an extent that all signals were affected, not only
those involved in the binding [20].
different anionic and neutral guests. The deviations of the data points
at ca. 5 equivalents, from the straight line connecting the origin and the
data points at 20 equivalents, describe the strength of binding. The
binding strength decreases from top to bottom. The dashed lines have
no physical significance but help to demonstrate the deviation from
linearity.
If most guests only bind very moderately, an exact (and tedious)
determination of all binding constants Kass is not interesting. It
13

Beilstein J. Org. Chem. 2012, 8, 11–17.
more extreme curvature, and thus, in this normalized form, the except in the case of the bulky TPPO. The affinities of concave
data points at 5 equivalents lie further away from the linear line host 1 lie in the following order: PyNO > DMSO > DPSO =
that connects the points corresponding to 0 and 20 equivalents.
MPSO > Cl− > TPPO. In contrast, the affinities of the non-
macrocyclic analogue 2 are: Cl− > PyNO = DMSO = TPPO >
The validity of this estimation has been checked with calcu- MPSO = DPSO (see Supporting Information File 1). When the
lated titration curves for different association constants Kass and plot was compared with the simulated titration curves (see
different maximum CIS (see Supporting Information File 1). Supporting Information File 1, page S12), Kass for the best
For an application on host 1, see Figure 3; for 2, see Figure 4. binder to 1, pyridine-N-oxide (PyNO), was estimated to be ca.
For each host, only those guests that are bound most strongly 40 M−1. A subsequent NMR titration of host 1 with PyNO
are listed. For the full data set, see Supporting Information provided an association constant of 25 M−1 (see Supporting
File 1. Data points below the straight line are physically mean- Information File 1). Remarkably, chloride ions are only very
ingless, and simply reflect the large errors for very weak weakly bound by concave host 1, and binding constants are
binding (the method of normalizing the shifts should preferably moderate anyway. A possible explanation may be a repulsion
not be carried out for guests with very small CIS).
between the negatively polarized oxygen atoms in the 2- and
6-positions of the bridge heads of 1 and the negatively, or
partially negatively charged guests.
Conclusion
1 is a readily synthesized concave host molecule in which the
isophthalamide moiety is the central binding unit, and it is
preorganized by its incorporation into the bi-macrocyclic struc-
ture. This concave host, although it does not exhibit strong
binding, is selective for negatively polarized oxygen atoms and
selects them according to the steric bulk of the guests. These
initial experiments now open the way for the synthesis of new
modified concave hosts based on isophthalamide units with im-
proved binding selectivity and/or for organocatalysis [21].
Concave host 1 can also be applied as a carrier in transport
experiments. When applied to chloride-loaded liposomes [22],
it showed twice as much transmembrane chloride transport with
respect to acyclic compound 2 (see Supporting Information
File 1). Even if the chloride binding is lower for concave host 1,
the transport through a bilayer membrane is faster. Additional
transport experiments are under investigation.
Figure 4: Normalized 1H NMR CIS (see text) for concave host 2 with
different anionic and neutral guests. The deviations of the data points
at ca. 5 equivalents, from the straight line connecting the origin and the
data points at 20 equivalents, describe the strength of binding. The
binding strength decreases from top to bottom. The dashed lines have
no physical significance but help to demonstrate the deviation from
linearity.
Experimental
General remarks
In Figures 3 and 4, the relative strengths of binding can be All reagents were obtained from commercial sources and used
obtained from the vertical deviations of the normalized CIS at without additional purification unless otherwise indicated.
ca. 5 equivalents from the straight line connecting the origin 5-tert-Butylisophthaloyl dichloride (3) was prepared from
and the values at 20 equivalents. The magnitude of the binding 5-tert-butylisophthalic acid and thionyl chloride according to
decreases from top to bottom.
Vögtle et al. [23]. 2,6-Bis(pent-4-enyloxy)aniline (4) was
prepared from 2-nitroresorcine according to Winkelmann et al.
By using this methodology, it is possible and easy to determine [16]. 2,6-Dimethoxyaniline (6) was synthesized from 2-nitrore-
the relative binding strengths of the two hosts 1 and 2 even for sorcine according to Mechoulam and Srebnik [24] and was
weak binding constants and situations where maximal chemi- finally reduced to 2,6-dimethoxyaniline (6) according to Franck
cally induced shifts Δδmax cannot be determined from only a and Kauffmann [25]. THF was freshly distilled from lithium
few measurements. When the two graphs for 1 and 2 with aluminium hydride (triphenylmethane as indicator). All reac-
different guests are compared, the different selectivity of the tions were carried out in an atmosphere of nitrogen. NMR
two hosts becomes evident. Concave host 1 shows a better spectra were recorded with Bruker AC 200, DRX 500 or AV
affinity for negatively polarized oxygen atoms than for anions, 600 instruments. Assignments are supported by COSY, HSQC
14

Beilstein J. Org. Chem. 2012, 8, 11–17.
and HMBC. All chemical shifts are referenced to TMS or C40H52N2O6 656.38251; found: 656.38257 (Δ = −0.1 ppm);
residual solvent peaks. Mass spectra were recorded with calcd for C3913CH52N2O6 657.38586; found: 657.38597 (Δ =
Finnigan MAT 8200 or MAT 8230. ESI mass spectra were −0.2 ppm); Anal. calcd for C40H52N2O6: C, 73.14; H, 7.98; N,
recorded with an Applied Biosystems Mariner Spectrometry 4.26; found: C, 73.04; H, 8.04; N, 4.39.
Workstation. IR spectra were recorded with Perkin-Elmer Spec-
trum 100 spectrometer, equipped with an ATR unit. Elemental Synthesis of 5-tert-Butyl-N,N'-bis(2,6-
analyses were carried out with a EuroEA 3000 Elemental dimethoxyphenyl)-isophthalamide (2)
Analyzer from Euro Vector. MALDI-TOF spectra were A solution of 5-tert-butylisophthaloyl dichloride (3, 550 mg,
recorded with Bruker-Daltonics Biflex III. 4-Chloro-α- 2.12 mmol) in tetrahydrofuran (5.00 mL) was added dropwise
cyanocinnamic acid (Cl-CCA) was used as the matrix. over 45 min to a stirred solution of 2,6-dimethoxyaniline (6)
(650 mg, 4.24 mmol) and triethylamine (2.35 mL, 1.72 g,
1H NMR experiments
17.0 mmol) in tetrahydrofuran (20 mL). The solution was
Each NMR tube was filled with 600 µL of a stock solution stirred for 24 h. The solvent and excess of triethylamine was
(5 mg/mL) of 1 or 2 in CD2Cl2, and subsequently ca. 5, and evaporated under reduced pressure. The residue was dissolved
later ca. 20 equivalents of the respective guest were added. The in chloroform (25 mL) and water (25 mL). The water phase was
exact amount was recalculated from the integrals by using extracted once with chloroform (25 mL), the combined organic
Bruker Topspin® 2.1. All experiments were carried out on a layer was dried with magnesium sulfate and evaporated under
Bruker AC 200 NMR equipped with an autosampler at 300 K. reduced pressure to yield a yellow solid, which was purified by
The spectra are referenced to the residual solvent peak.
column chromatography (silica gel, dichloromethane/methanol,
40:1, Rf = 0.11) to give 2 as a white solid (1.02 g, 2.07 mmol,
97%); mp 122 °C; 1H NMR (500 MHz, CDCl3) δ 8.24 (s, 1H,
Ar1-2-H), 8.14 (s, 2H, Ar1-4,6-H), 7.43 (br. s, 2H, NH), 7.21 (t,
3J = 8.4 Hz, 2H, Ar2-4-H), 6.62 (d, 3J = 8.4 Hz, 4H, Ar2-3,5-
H), 3.84 (s, 12H, OCH3), 1.38 (s, 9H, CH3); 13C NMR
Synthesis of 255-tert-Butyl-2,11,13,22-tetraoxa-
23,27-diaza-1,12 (1,3,2)-25 (1,3)-
tribenzenabicyclo[10.10.5]heptacosaphan-24,26-
dione (1)
A solution of 255-tert-Butyl-2,11,13,22-tetraoxa-23,27-diaza- (125 MHz, CDCl3) δ 165.8 (C=O), 155.1 (Ar2-2,6-C), 152.4
1,12(1,3,2)-25(1,3)-tribenzenabicyclo[10.10.5]heptacosaphan- (Ar1-5-C), 134.7 (Ar1-1,3-C), 128.2 (Ar1-4,6-C), 127.6 (Ar2-4-
6,17-dien-24,26-dione (186 mg, 284 µmol), Pd/C (10%, C), 123.4 (Ar1-2-C), 114.6 (Ar2-1-C), 104.4 (Ar2-3,5-C), 56.0
150 mg) and methanol (30 mL) was stirred under an atmos- (OCH3), 35.1 (C(CH3)3), 31.3 (q, CH3); IR (ATR) : 3387 (w,
phere of hydrogen for 24 h. The mixture was filtered through a NH), 3231 (w, arom. CH), 2947 (m, aliph. CH), 1663 (m,
syringe filter (0.450 µm) to remove all Pd/C, and the solvent C=O), 1593 (m, arom. C=C), 1519 (s, arom. C=C) cm−1; EIMS
was removed under reduced pressure to obtain 1 as a white (70 eV): m/z (% relative intensity) 492 (83) [M]+•, 340 (100)
solid (144 mg, 219 µmol, 77%); mp 225 °C (decomp.); [M − C8H10NO2]+; CIMS (isobutane): m/z (% relative
1H NMR (500 MHz, CDCl3) δ 8.30 (s, 2H, 254,6-H), 8.06 (s, intensity) 493 (100) [M + H]+. Anal. calcd for
1H, 252-H), 7.24 (br. s, 2H, NH), 7.14 (t, 3J = 8.4 Hz, 2H, C28H32N2O6·0.1CH2Cl2: C, 67.36; H, 6.48; N, 5.59; found: C,
15,125-H), 6.59 (d, 3J = 8.4 Hz, 4H, 14,6,124,6-H), 4.19 (ddd, 2J 67.42; H, 6.53; N, 5.74.
= ca. 9 Hz, 3J = ca. 9 Hz, 3J = ca. 2 Hz, 4H, OCHaHb), 3.85
(ddd, 2J = 9.7 Hz, 3J = 9.7 Hz, 3J = 2.1 Hz, 4H, OCHaHb), 1.79 Synthesis of N,N'-Bis(2,6-bis[pent-4-enyloxy]-phe-
(mc, 4H, OCH2CHaHb), 1.62 (mc, 4H, OCH2CHaHb), 1.43 (s, nyl)-5-tert-butyl-isophthalamide (5)
9H, CH3), 1.32 (mc, 8H, CH2), 1.25 (mc, 8H, CH2); 13C NMR In 20 mL anhydrous tetrahydrofuran, 2,6-bis(pent-4-
(125 MHz, CDCl3) δ 165.4 (s, C=O), 154.0 (s, 11,3,121,3-C), enyloxy)aniline (4, 1.95 g, 7.46 mmol) and anhydrous triethyl-
153.3 (s, 255-C), 134.8 (s, 251,3-C), 129.6 (d, 254,6-C), 127.1 (d, amine (4.14 mL, 3.02 g, 29.7 mmol) were dissolved. A solution
15,125-C), 121.1 (d, 252-C), 115.6 (s, 12,122-C), 105.4 (d, 14,6, of 5-tert-butylisophthaloyl dichloride (3) (970 mg, 3.75 mmol)
124,6-C), 69.2 (t, OCH2), 35.3 (s, C(CH3)3), 31.2 (q, CH3), 30.6 in anhydrous tetrahydrofuran (10 mL) was added dropwise. The
(t, OCH2CH2), 29.7 (t, O(CH2)3CH2), 27.4 (t, O(CH2)2CH2); solution was stirred for 16 h at room temperature. The solvent
IR (ATR) : 3430 (w, NH), 2930, 2848 (2 w, aliph. CH), 1683 and excess of triethylamine were evaporated under reduced
(m, C=O), 1589 (w, arom. C=C), 1509 (m, arom. C=C),1392 (s, pressure and the residue was dissolved in chloroform (25 mL)
CH3) cm−1. EIMS (70 eV): m/z (% relative intensity) 656 (100) and water (25 mL). The aqueous phase was extracted with chlo-
[M]+•; CIMS (isobutane): m/z (% relative intensity) 657 (30) [M roform (25 mL). The organic layers were collected, dried with
+ H]+; ESIMS (CHCl3): m/z (% relative intensity) 679 (100) [M magnesium sulfate and the solvent was evaporated under
+ Na]+, 657 (75) [M + H]+; MS (MALDI-TOF, Cl-CCA): m/z reduced pressure. The product was isolated by column chroma-
695 [M + K]+, 679 [M + Na]+, 656 [M]+; HRMS calcd for tography (silica, cyclohexane/ethyl acetate, 1:1, Rf = 0.34) as a
15

Beilstein J. Org. Chem. 2012, 8, 11–17.
white solid (1.63 g, 2.30 mmol, 61%); mp 136 °C; 1H NMR this 13C spectrum. MS (MALDI-TOF, Cl-CCA): m/z 676 [M +
(500 MHz, CDCl3) δ 8.18 (s, 1H, Ar1-2-H), 8.08 (s, 2H, Ar1- Na]+, 654 [M + H]+.
4,6-H), 7.28 (br. s, 2H, NH), 7.16 (t, 3J = 8.4 Hz, 2H, Ar2-4-H),
6.59 (d, 3J = 8.4 Hz, 4H, Ar2-3,5-H), 5.78 (ddt, 3J = 16.9 Hz, 3J
Supporting Information
= 10.2 Hz, 3J = 6.6 Hz, 4H, CH=CH2), 4.97 (mc, 4H, HZ), 4.91
(mc, 4H, HE), 4.01 (t, 3J = 6.5 Hz, 8H, OCH2), 2.16 (mc, 8H,
NMR spectra and product analyses for 1 and 2 are available
CH2CH=CH2), 1.85 (mc, 8H, OCH2CH2), 1.38 (s, 9 H,
in the Supporting Information as well as details of the
CH3).13C NMR (125 MHz, CDCl3) δ 166.1 (s, C=O), 154.8 (s,
NMR CIS titrations, the evaluation of the normalized CIS
Ar2-2,6-C), 152.3 (s, Ar1-5-C), 137.6 (d, CH=CH2), 135.4 (s,
method, 1H,1H NOESY experiments, and the transport
Ar1-1,3-C), 127.6 (d, Ar1-4,6-C), 127.6 (d, Ar2-4-C) 123.3 (d,
experiments.
Ar1-2-C), 115.1 (t, CH=CH2), 106.2 (s, Ar2-1-C), 105.4 (d, Ar2-
Supporting Information File 1
3,5-C), 68.1 (t, OCH2), 35.1 (s, C(CH3)3), 31.2 (q, CH3), 30.1
(t, CH2CH=CH2), 28.4 (t, OCH2CH2); IR (ATR) : 3207 (br.
w, NH), 3076 (w, arom. CH), 2946 (m, aliph. CH), 1669 (m,
C=O), 1647 (m, aliph. C=C), 1589 (m, arom. C=C), 1520 (s,
arom. C=C) cm−1; EIMS (70 eV): m/z (% relative intensity) 709
(49) [M]+•, 708 (100) [M − H]+; CIMS (isobutane): m/z (%
Product analyses and experimental data.
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-8-2-S1.pdf]
relative intensity) 710 (25) [M + H]+, 709 (59) [M]+•, 708 (100) Acknowledgements
[M − H]+; ESIMS (CHCl3): m/z (% relative intensity) 732 (25) We thank Dr. Roberto Quesada, University of Burgos, Spain,
[M + Na]+; HRMS: calcd for C44H56N2O6: 708.41382; found: for the chloride transport experiments, and the EU for its
708.41390 (Δ = −0.1 ppm); calcd for C4313CH56N2O6: support through the Marie Curie Research Training Network
709.41718; found: 709.41706 (Δ = 0.2 ppm). Anal. calcd for MRTN-CT-2006-035614 Dynamic Combinatorial Chemistry
C44H56N2O6·0.3C6H12·0.3C4H8O2: C, 74.18; H, 8.24; N, 3.66; (DCC).
found: C, 73.95; H, 7.93; N, 4.04.
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23,27-diaza-1,12(1,3,2)-25(1,3)-
tribenzenabicyclo[10.10.5]heptacosaphan-6,17-
dien-24,26-dione
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2121–2123. doi:10.1039/b703905k
of N,N'-bis-(2,6-bis[pent-4-enyloxy]-phenyl)-5-tert-butyl-iso-
phthalamide (5, 1.00 g, 1.41 mmol) and Grubbs Catalyst 1st
gen. (162 mg, 141 µmol). The solution was stirred for 24 h at
room temperature. The reaction was quenched with ethyl vinyl
ether (2 mL) and the mixture was stirred for 1 h. The solvent
was removed under reduced pressure and the crude product was
filtered over silica gel (1 cm, dichloromethane/methanol, 40:1).
The solvent was removed and cyclohexane/ethyl acetate
(150 mL, 1:1, v/v) was added to crystallize the product. The
product was filtered off and washed with ethyl acetate (10 mL)
to obtain a white solid (186 mg, 284 µmol, 20%). 1H NMR
(500 MHz, CDCl3) δ 8.25 (s, 2H, 254,6-H), 7.98 (s, 1H, 252-H),
7.20 (br. s, 2H, NH), 7.15 (t, 3J = 8.3 Hz, 2H, 15,125-H), 6.61
(d, 3J = 8.3 Hz, 4H, 14,6,124,6-H), 5.36–5.27 (m, 4H, CH=CH),
4.22–3.82 (m, 8H, OCH2), 2.20–1.60 (m, 16H, CH2), 1.42 (s,
9H, CH3) ppm; 13C NMR (125 MHz, CDCl3) δ 154.2 (s,
11,3,121,3-C), 153.8 (s, 255-C), 134.6 (s, 251,3-C), 130.3 (s,
CH=CH), 129.6 (d, 254,6-C), 127.0 (d, 15,125-C), 121.7 (d, 252-
C), 116.1 (s, 12,122-C), 105.4 (d, 14,6,124,6-C), 69.5 (t, OCH2),
35.3 (s, C(CH3)3), 31.2 (q, CH3), 30.7 (t, OCH2CH2), 24.9 (t,
O(CH2)2CH2); The C=O signal was too weak to be detected in
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