Synthesis of glycoluril-tetrathiafulvalene molecular clips for electron-deficient neutral guests through a straightforward Diels-Alder strategy

Article abstract of DOI:10.1039/c4nj00617h

An electroactive molecular clip incorporating tetrathiafulvalene (TTF) sidewalls grafted on a glycoluril platform has been synthesized using a straightforward Diels-Alder strategy. This way of attachment to the glycoluril U-shape scaffold afforded a rigidified and closed receptor for which the electron-rich TTF pincers are expected to be at a suitable distance for sandwiching neutral guests through donor-acceptor interactions. The efficient complexation ability of this host architecture toward one molecule of tetracyanoquinodimethane derivative (F₄-TCNQ) in solution has been demonstrated using cyclic voltammetry and UV-Visible titration methods.

Full text of DOI:10.1039/c4nj00617h

NJC
View Article Online
View Journal
PAPER
Synthesis of glycoluril-tetrathiafulvalene
molecular clips for electron-deficient neutral
guests through a straightforward Diels–Alder
strategy†
Cite this:DOI: 10.1039/c4nj00617h
Marie Hardouin-Lerouge, Yoann Cotelle, Stephanie Legoupy and
´
Pietrick Hudhomme*
´
An electroactive molecular clip incorporating tetrathiafulvalene (TTF) sidewalls grafted on a glycoluril
platform has been synthesized using a straightforward Diels–Alder strategy. This way of attachment to
the glycoluril U-shape scaffold afforded a rigidified and closed receptor for which the electron-rich TTF
pincers are expected to be at a suitable distance for sandwiching neutral guests through donor–acceptor
interactions. The efficient complexation ability of this host architecture toward one molecule of tetracyano-
Received (in Montpellier, France)
18th April 2014,
Accepted 26th August 2014
DOI: 10.1039/c4nj00617h
4
quinodimethane derivative (F -TCNQ) in solution has been demonstrated using cyclic voltammetry and
www.rsc.org/njc
UV-Visible titration methods.
redox-active units into host molecules should increase inter-
molecular donor–acceptor interactions. In this context, the use
Introduction
Since the last two decades, the rapid expansion in supra- of tetrathiafulvalene (TTF) appears particularly attractive thanks to
molecular chemistry has resulted in the synthesis of molecular its p-electron donor ability resulting in the formation of famous
8
receptors prone to act as efficient host–guest systems with the donor–acceptor complexes. More recently, this electron donor
capability of recognizing specific chemical species through weak framework has proven to be an efficient electroactive brick in
1
non-covalent interactions. Considerable efforts are currently various topics of supramolecular chemistry ranging from electro-
devoted to the extension of supramolecular principles for cata- chemical sensing to switchable architectures, in particular thanks
2
lysis, biological and biomedicinal applications and for the to its peculiar electronic characteristics with its two successive
3
9
development of molecular devices and machines. While the reversible oxidation steps giving rise to three stable redox states.
10
selective recognition of cations and anions have attracted con- Despite the broad development of TTF chemistry, only a few
siderable research interest in terms of applications in various number of TTF-based molecular clips built around a more or less
areas of supramolecular chemistry, the development of molecular rigidified scaffold have been synthesized and employed for sensing
sensors devoted to neutral molecules using host–guest inter- neutral guests. For example, the calix-[4]pyrrole platform decorated
actions remains a real challenge. In this area of interest, the with four appended TTF units was shown to act in its 1,3-alternate
concept of molecular clips and tweezers opens a fascinating field conformation as a sandwich-like host molecule for different
of research for this molecular recognition of neutral guests electron-deficient guests with the ability of releasing the guest by
4
11
exploring the potentialities of donor–acceptor interactions. Since addition of chloride anions. A calix[2]pyrrole[2]thiophene based
the pioneering work of Chen and Whitlock using caffeine units architecture incorporating two TTF units was described and its
5
12
linked to a flexible linker, intensive research was initially devel- ability to function as a receptor for TCNQ was achieved.
6
7
oped by Zimmerman, Kl ¨a rner and their collaborators focusing Preorganized calix[4]arene-pyrrolotetrathiafulvalene derivatives
on the use of a rigidified spacer for orienting acridine or polyarene were also recently investigated as efficient receptors for sensing
as weak p-donating interaction sites. Among strategies available electron-deficient neutral molecules with the formation of charge-
for enhancing the guest recognition process, the incorporation of transfer complexes in solution. Molecular clips containing two
TTF moieties connected to the opposite sides of a 1,2,4,5-
13
substituted benzene backbone through eight-membered dithia
Universit ´e d’Angers, Laboratoire MOLTECH-Anjou, CNRS UMR 6200,
rings were described as relatively rigid sensors able to adopt a
2
Bd Lavoisier, 49045 Angers, France. E-mail: pietrick.hudhomme@univ-angers.fr
14
special cis-conformation for recognition of neutral guests.
†
Electronic supplementary information (ESI) available: Experimental proce-
The glycoluril-based scaffold historically developed by Nolte
and colleagues has become a very popular building block for
dures, characterization data, electrochemical and UV-Visible titration results.
See DOI: 10.1039/c4nj00617h
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem.

View Article Online
Paper
NJC
Reaction using DDQ was carried out in DMF to provide com-
pound 5 in 65% yield, but this could be finally improved to
reach 91% in THF instead of DMF.
Secondly, compound 5 was used as a bis-dienophile in a
[4+2] cycloaddition reaction. Reductive elimination upon treat-
ment of TTF derivative 6 with potassium iodide in the presence
2
1
of 18-crown-6 gave rise in situ to transient diene 7. Following
our experience in the efficient reactivity of such TTF-based
2
2
23
diene toward dienophiles such as fullerene C60 or quinone
2
4
derivatives, the concomitant two Diels–Alder cycloadditions
were carried out by trapping 2,3-dimethylidene-[2H]TTF 7 with
bis-dienophile 5 at room temperature in THF. Under these
experimental conditions, bis-cycloadduct 8 was not isolated
and complete aromatization occurred subsequently, without
using supplementary DDQ reagent. It should be noted that
Scheme 1 TTF and glycoluril-based molecular clips 1 and 2.
the preparation of rigidified molecular clips for binding such a complete dehydrogenation phenomenon was previously
aromatic guests inside the cavity thanks to a suitable preorgani- observed when tetrakis(bromomethyl)benzene was reacted with
1
5
25
zation of the aromatic binding sites. To our knowledge, only 2,3-dimethylbenzoquinone in the presence of sodium iodide.
receptor 2 built around the glycoluril platform and incorporating Molecular clip 1 was isolated as a green powder in 20% yield
TTF sidewalls has been described before we started to investigate after purification by column chromatography on silica gel using
this topic. Molecular clip 2 was synthesized by an acid-catalyzed CH Cl /EtOAc (95 : 5) as the eluent. During our investigations
2
2
condensation followed by a cross-coupling to link the glycoluril around this Diels–Alder reaction, we observed that the aroma-
scaffold to the TTF arms. This host 2 was shown to complex an tization could occur during the silica gel treatment. With the
electron-deficient bipyridinium guest such as a paraquat type aim of improving the yield of this cycloaddition, we turned our
1
6
molecule (Scheme 1).
attention to the replacement of potassium iodide with com-
Using an alternative synthetic strategy involving a [4+2] mercial iodo-ionic liquid BMI-I (1-butyl-3-methylimidazolium
2
6
cycloaddition reaction, we describe in this paper the straight- iodide) as the halogen source. Unfortunately, despite a lot of
forward synthesis of new glycoluril-based molecular clip 1. efforts devoted to this reaction, we did not succeed in signifi-
Such a strategy allows integration of TTF derivatives presenting cantly improving the yield of molecular clip 1 (21% yield with
1
13
a larger p-extension as sidewalls, in order to increase inter- BMI-I). H and C NMR spectra are in agreement with the
molecular interactions with planar aromatic guests. An addi- achievement of molecular clip in the aromatized structure.
1
tional interest of this new electron-rich clip relies on an The H spectrum of compound 1 (ESI†) showed the character-
excellent solubility in various solvents due to the presence of istic signals corresponding to the TTF-protected hydroquinone
bulky 1,4-bis(tert-butyldiphenylsilyloxy)ether groups, which prevent moieties, two doublets corresponding to the CH
2
–N glycoluril
2
the usual dimeric packing preference of glycoluril-based molecular platform with an expected coupling constant ( J = 16.5 Hz), and
17
clips. The nature of receptor 1 makes it a potentially versatile finally, a singlet signal at 7.90 ppm corresponding to the protons
scaffold for studying donor and acceptor interactions between TTF resulting from the aromatization reaction. The MALDI-TOF mass
and neutral electron-deficient guests. Highly efficient recognition spectrum exhibited the molecular peak thus confirming the
properties of molecular clip 1 toward the neutral molecule aromatization of the molecular clip. Unfortunately, all attempts
tetrafluoro-tetracyanoquinodimethane (F
4
-TCNQ) are described. at growing single crystals of molecular clip 1 for X-ray diffraction
studies have been unsuccessful so far. Consequently, theoretical
calculations were realized using a semi-empirical AM1 method
on molecular clip 1 without silylated groups on the hydro-
quinone moieties as a simplified model. The geometry optimization
Results and discussion
The synthesis of molecular clip 1 consists in using as a key-step confirmed the expected quasi-planarity of the fused TTF-
the Diels–Alder cycloaddition between glycoluril–diquinone naphthoquinone unit constituting the arm of the molecular
skeleton 5 acting as the bis-dienophile and 2,3-dimethylidene- clip. The angle a defining the tapering cavity of the clip was
[
2H]TTF 7 playing the role of the diene (Scheme 2). First, determined to be close to 311 taking into account the two mean
1
8
compound 4 was prepared according to the literature starting planes of the TTF-naphthoquinone arms (Fig. 1). Moreover, the
from known glycoluril derivative 3 by treatment with an excess distance between both TTF central double bonds was estimated
of hydroquinone in 1,2-dichloroethane. An aerial oxidation of to be equal to 9.7 Å thus giving a rating of the cavity size.
compound 4 using CuCl as a catalyst in the presence of pyridine This system was shown to act as an effective receptor for
in DMSO solution was previously reported by Nolte and colleagues neutral electron acceptors and the complexation ability of clip 1
1
9
15b
for the synthesis of compound 5 in 75% yield. We present here toward the neutral guest, such as F
4
-TCNQ, was evaluated by
a new competitive method for the synthesis of 5 by using DDQ cyclic voltammetry and UV-Vis spectroscopy using electro-
2
0
as a dehydrogenation reagent of hydroquinone moieties.
chemical and optical responses of both quinone and TTF units.
New J. Chem.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014

View Article Online
NJC
Paper
Scheme 2 Synthesis of molecular clip 1.
À4
Fig. 2 Cyclic voltammogram for molecular clip 1: 5 Â 10 M in CH
2 2
Cl /
Fig. 1 Geometry optimization of the analog of molecular clip 1 (without
silyl protecting groups of the hydroquinone units as a simplified model).
3 4 6
CH CN (9/1) in n-Bu NPF 0.1 M. Pt as the working and counter electrode,
+
À1
Ag/Ag reference electrode, scan rate 100 mV s . Values are given vs. SCE,
+
the couple Fc/Fc (0.405 V vs. SCE) being used as an internal reference.
The electrochemical properties of molecular clip 1 were
4
+
2 2 3
investigated by cyclic voltammetry (CV) in CH Cl /CH CN (9/1) could be assigned to inter-TTF interactions at the 1 oxidized
solution using n-Bu NPF 0.1 M as the electrolyte (Fig. 2). As state. One reversible two-electron reduction process was shown
4
6
expected, the CV of molecular clip 1 showed two redox oxidation for the p-benzoquinone (Q) moiety at Ered1 = À0.76 V vs. SCE
À
ꢀ
processes characteristic of the TTF moiety. These two one- corresponding to the generation of the anion radical Q species
electron oxidation waves at Eox1 = +0.67 V and Eox2 = +1.15 V on each acceptor unit. The coalescence of these reduction waves
vs. SCE correspond to the successive generation of the cation for both quinone units suggested that no effective electronic
2
7
radical and dication of each TTF moiety, respectively (Fig. 1). coupling between both Q centres occurred.
Whereas the first oxidation wave appears as a reversible process, The electrochemical detection of a neutral guest by using a
the noticeable broader and non-reversible second redox wave redox-active host has attracted less attention with only a few
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem.

View Article Online
Paper
NJC
Fig. 5 Electrostatic potential surfaces (EPS) of molecular clip 1 (left) and
F
4
-TCNQ (right) showing that the electrostatic potential of the TTF arms is
negative (shown in red), whereas the EPS of the F -TCNQ guest molecule
is calculated to be highly positive (shown in blue).
4
À4
Fig. 3 Cyclic voltammograms of molecular clip 1 [2.5 Â 10
M in
-TCNQ
using a B3LYP functional density approach with 6-31+G(2d,2p) basis
sets. The EPS was shown to be negative on both TTF arms and,
CH
2
Cl
2
/CH
3
CN (9/1) in n-Bu
4
NPF
6
0.1 M] upon addition of F
4
À2
À1
aliquots [10 M in CH
2
Cl
2
/CH
3
CN (7/3)], scan rate: 100 mV s . The two
hence, complementary to the EPS of the electron-deficient F -TCNQ
4
4
reduction waves correspond to the second reduction wave of F -TCNQ
and the first reduction wave for the quinone moiety at À0.22 V and guest molecule (Fig. 5). Nevertheless, the strong negative EPS on the
À0.76 V vs. SCE, respectively.
oxygen atoms of all carbonyl functions constituting the glycoluril–
diquinone scaffold should be noted.
The optical properties of molecular clip 1 were investigated
examples reported in the literature compared to the more
À5
using UV/Vis spectroscopy in 10
2 2
M solution in CH Cl .
2
8
established detection of cations or anions. We were interested
in using the cyclic voltammetry technique considering that the
first oxidation and reduction waves of TTF and quinone, respec-
tively, of the molecular clip constitute two possible signals to probe
the recognition process.
Binding studies were performed by progressive addition of
4
the F -TCNQ acceptor to the solution of the receptor and
determination of the binding was followed on both first oxida-
tion or reduction waves of the clip and also on the reduction
waves of the guest. Whereas no clear modification was observed
21
Compound 5 and silylated protected TTF-dihydroquinone 9
Scheme 2) were used as references. Whereas the spectrum of
the TTF derivative showed two absorption bands at 265 and
14 nm characteristic of the TTF core, a large absorption band
(
3
between 350 and 450 nm could be attributed to an intra-
molecular charge transfer interaction between conjugated
TTF and quinone moieties in compound 1. Moreover, the green
color of clip 1 could be explained by the presence of a large but
À1
À1
low intense absorption band (e = 1000 L mol cm ) between
5
00 and 700 nm (Fig. 6).
The binding affinity of molecular clip 1 was studied by
4
on the first oxidation waves of TTF and F -TCNQ units, a
significant shift of the first reduction wave of the quinone unit
to a less negative potential was observed, resulting from a more
difficult reduction of the quinone moiety (Fig. 3).
UV-Visible titration with the acceptor F -TCNQ in CH Cl ,
4
2
2
which is characterized by an important absorption band at
86 nm. Addition of aliquots of molecular clip 1 in CH Cl
2
3
2
The progressive addition of F
of the first two-electron reduction wave of the quinone moiety with
DE close to 20 mV for one equivalent of F -TCNQ (Fig. 4). This
4
-TCNQ resulted in a positive shift
showed the formation and increase of bands at 760 and 860 nm
which could be attributed to the progressive formation of the
4
30
4
F -TCNQ radical anion (Fig. 7). The increase of the band at
significant change in the electronic properties of the electroactive
units of the molecular clip constitutes one of the few examples of
around 625 nm was attributed to the cumulative contribution
29
neutral guest recognition evidenced by cyclic voltammetry.
These results are in agreement with the electrostatic potential
surface (EPS) of clip 1 determined by quantum chemical calculations
Fig. 6 UV-Visible absorption spectra of compounds 1 (black), 5 (red) and
red
1
À5
Fig. 4 Plot of the shift of the first reduction E
of molecular clip 1 with
9 (blue) in 10
2 2
M CH Cl solution. In the inset, enlargement of the
4
added equivalents of F -TCNQ.
UV-Visible spectrum of compound 1.
New J. Chem.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014

View Article Online
NJC
Paper
À5
Fig. 7 UV-Visible absorption spectra of F
4
-TCNQ (CH
Cl
2 2
, 10 M) upon
À4
titration with molecular clip 1 (CH
2
Cl
2
, 5 Â 10 M). Inset: enlargement of
the absorption spectra between 500 and 1000 nm.
1
Fig. 9 Top: H NMR spectra (CD
2
Cl
2
) of molecular clip 1 (extension
around 7.90 ppm) alone (A) and after addition of F
(
4
-TCNQ: 0.1 molar eq.
B); 0.4 molar eq. (C); 1 molar eq. (D); bottom: F NMR spectra (CD Cl ) of
-TCNQ alone (E) and after its addition to the molecular clip in the
Fig. 8 Visual color change of molecular clip 1 induced by the addition of
19
2
2
À4
F
F
4
-TCNQ: solutions in CH
2
Cl
2
(C = 2.5 Â 10 M) of molecular clip 1 (left),
F
4
4
-TCNQ (centre) and clip: F
4
-TCNQ complex in 1 : 1 stoichiometry (right).
stoichiometry 1 : 1 molar (F).
of the increasing amount of neutral clip 1 and the formation of the generation of some paramagnetic species. Such rapid loss
1
9
TTF cation radical species. Chemical oxidation of molecular of the NMR F signal of F -TCNQ in CDCl has been recently
4
3
clip 1 in CH Cl solution was carried out by successive aliquot reported when small amounts of regioregular poly(3-hexyl-
2
2
addition of NOSbF
6
used as an oxidizing reagent, thus con- thiophene) donor polymer were added. This phenomenon
firming the absorption band of the TTF cation radical at around originated from the formation of minority paramagnetic species
3
1
6
25 nm (ESI).
As can be seen in Fig. 8, the addition of F
an immediate color change of the CH Cl
resulting from charge transfer interaction and showing an
-TCNQ resulted in efficient doping of the polymer.
3
2
4
2
2
solution from pale
Quantitative measurements were performed by monitoring
-TCNQ
upon addition of sensor 1 (Fig. 10). To quantify the supramolec-
This study of the electronic interaction between the TTF ular host:guest interaction, the association constant was deter-
yellow-green to intense green, this observation being assignable the changes in the UV-Visible spectra at 860 nm of F
to the formation of a charge-transfer complex.
4
3
3
4
sidewalls of the receptor and the acceptor F -TCNQ guest was mined from this titration experiment. The association constant
complemented by H and F NMR spectra which also high-
lighted the complexation of F
The H NMR signal at 7.90 ppm, corresponding to the aromatic were calculated by the fit of the binding isotherm complexation
proton median between TTF and quinone units, gradually curve performed with all the points of Fig. S10 (ESI†). Such a
decreased then disappeared until the addition of one equiva- high binding value confirms that this rigidified molecular clip 1
1
19
4
4
À1
K
a
= 2.4 Â 10 (Æ0.1 Â 10 ) M in CH
2 2
Cl and the molar
À1
À1
4
-TCNQ using receptor 1 (Fig. 9). extinction coefficient of the complex (e = 975 Æ 20 L mol .cm
)
1
1
9
lent of F -TCNQ guest. Similarly, the F NMR signal character- is an efficient receptor for the F -TCNQ acceptor, and this value
4
4
3
istic of F -TCNQ also disappeared (see full spectrum in the has to be compared with the association constant K = 5.6 Â 10
4
a
3
À1
ESI†) when this guest was added in stoichiometric quantity to (Æ0.3 Â 10 ) M determined for interaction between molecular
1
6b
the molecular clip in CD
gested the presence of a charge or electron transfer interaction
between both electroactive TTF and F -TCNQ units resulting in with the 1 : 1 binding stoichiometry between clip 1 and F
2
Cl
2
solution. This observation sug- clip 2 and paraquat.
The construction of the corresponding Job plot corroborates
-TCNQ
4
4
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem.

View Article Online
Paper
NJC
sidewalls has been realized using an efficient Diels–Alder
cycloaddition approach. This rigid and preorganized molecular
receptor is expected to display efficient sensing ability toward
neutral guests. We showed strong binding with the acceptor
F4-TCNQ in solution using cyclic voltammetry and UV-Visible
titrations, giving a particular deeply coloured charge transfer
complex. This result opens promising perspectives for design-
ing and constructing a wide variety of novel receptor architec-
tures. Binding studies with a wide variety of electron-poor
guests using such electron-rich molecular clips are currently
underway.
Fig. 10 UV-Visible titration curve obtained from titration of F
4
-TCNQ
À5
) with molecular clip 1 (C = 5 Â 10À4 M in CH
(C = 10 M in CH
Cl
2 2
2 2
Cl )
at 860 nm.
Experimental
General methods
The following chemicals were obtained commercially and were
used without any purification. Dry solvents were obtained by
distillation over suitable dessicants (THF from Na/benzophe-
none). Reactions were monitored by thin-layer chromatography
on aluminium sheets coated with silica gel 60 F254. Flash
chromatography was performed with silica gel 60A (40–60 mm).
Melting points were determined using a Reichert-Jung micro-
1
13
scope and are uncorrected. H NMR and C NMR spectra were
1
13
recorded on Bruker Avance III 300 ( H: 300 MHz; C: 75 MHz)
spectrometer. Chemical shifts (d) are reported in ppm relative to
residual CHCl or CH Cl . IR spectra were recorded on a Bruker
3 2 2
Vertex 70 spectrophotometer. UV-Visible experiments were per-
formed using Perkin Elmer Lambda 19 NIR and 950 spectrometers.
Matrix-assisted laser-desorption/ionization mass spectrometry was
performed using a Bruker Daltonics BIFLEX III spectrometer by
using dithranol as the matrix. The high resolution mass spectrum
Fig. 11 Job plot at 860 nm for F
4
-TCNQ vs. molecular clip 1 at room
Cl ) consistent with a 1 : 1 binding
À5
temperature (C = 10
M in CH
2
2
stoichiometry.
(
HRMS) was recorded using a LTQ Orbitrap (Thermo Scientific)
with a maximum centered at a molar ratio of 0.5 (Fig. 11). This
Job plot demonstrates that the phenomenon does not result
from a redox reaction involving the exchange of one electron
under electrospray ionization (ESI) in positive ionization mode.
Cyclic voltammetry was carried out in a three-electrode cell
equipped with a platinum millielectrode as the working electrode,
a platinum wire counter electrode and a silver wire in a 0.01 M
solution of AgNO in CH CN as a reference electrode. The electro-
lytic media involved a 0.1 M solution of tetra-n-butylammonium-
hexafluorophosphate (TBAHP – puriss quality) in CH CN. The
ferrocene/ferrocenium couple (Fc/Fc ) was used as an internal
reference and the potentials were expressed versus a saturated
calomel electrode (SCE) as a reference. All experiments were
performed in a glove box containing dry, oxygen-free (o1 ppm)
argon, at room temperature. Electrochemical experiments were
carried out using an EGG PAR 273A potentiostat.
between TTF and F -TCNQ. Indeed, given that both TTF units are
4
oxidized to the cation radical state at the same potential, a Job
plot with a 1 : 2 binding stoichiometry would have been obtained
in such a hypothesis. This definitively confirms the inclusion of
3
3
4
F -TCNQ inside the cavity of the clip.
3
+
This result demonstrates that the size of the extended cavity
presented here constitutes a fundamental parameter for binding
the F -TCNQ guest. For comparison, Nolte and colleagues have
4
clearly shown using a glycoluril based receptor incorporating
2,7-dimethoxynaphthalene walls that steric effects play an impor-
tant role. If the dimensions of the cavity of the clip are not
sufficient, charge transfer complexes are obtained with TCNQ or
1
5c
Synthetic procedures
TCNE but these acceptors are not bound in its cavity. Molec-
ular clip 1 constitutes one of the rare examples of architectures
Compound 5
exhibiting good affinity for sandwiching F -TCNQ as a proto-
typical electron-poor guest.
4
Method A. To a solution of compound 4 (200 mg; 0.35 mmol)
in THF (20 mL) was added DDQ (340 mg; 1.5 mmol). The
reaction mixture was stirred at room temperature for 30 min
under an argon atmosphere. After addition of water (20 mL),
3
4
Conclusions
the reaction mixture was extracted with CH
2
Cl
2
. The organic
and
based molecular clip including electroactive tetrathiafulvalene the solvent was removed under vacuum. The residue was
In conclusion, an original and straightforward synthesis of glycoluril- layer was washed with water (3 Â 20 mL), dried over MgSO
4
New J. Chem.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014

View Article Online
NJC
Paper
purified by chromatography on silica gel (eluent: CH
affording after precipitation using diethyl ether compound 5
2
Cl
2
)
Acknowledgements
This work was supported by the French National Research
Agency in the frame of the program ANR PNANO entitled
TTF-based Nanomat (ANR-07-NANO-030-01). We thank the
French Ministry of Higher Education and Research for PhD
grants to M. Hardouin-Lerouge and Y. Cotelle. We gratefully
acknowledge Dr Ingrid Freuze (platform PIAM, University of
Angers) for her assistance in mass spectrometry experiments.
as a pink powder (180 mg; 91% yield).
Method B. To a solution of compound 4 (185 mg, 0.33 mmol)
in DMSO (5 mL) was added CuCl (25 mg, 0.25 mmol) and
pyridine (0.25 mL). The solution was stirred for 2 h at room
temperature with an air bubble in the solution. After addition
of chloroform, the organic phase was successively washed with
a 1 M HCl aqueous solution (50 mL) then 5% ammonia solution
(
2 Â 50 mL), dried over MgSO
4
, and the solvent was removed
Notes and references
under vacuum. The residue was purified by precipitation in a
mixture of CH
141 mg, 76%).
Cl
2 2
and petroleum ether to afford compound 5
1
2
3
J. W. Steed and J. L. Atwood, Supramolecular Chemistry, John
Wiley & Sons Ltd, 2nd edn, 2009.
(
1
M.p 4 230 1C. H NMR (CDCl ) d: 7.14–7.17 (m, 6H, H
3
P. J. Cragg, Supramolecular Chemistry: From biological
inspiration to biomedical applications, Springer, 2010.
(a) E. R. Kay, D. A. Leigh and F. Zerbetto, Angew. Chem., Int.
Ed., 2007, 46, 72; (b) S. Saha and J. F. Stoddart, Chem. Soc.
Rev., 2007, 36, 77; (c) Special Issue: Molecular Machines and
Switches, Adv. Funct. Mater., 2007, 17, 671.
phenyl), 6.98–7.01 (m, 4H, H phenyl), 6.74 (s, 4H, H quinone),
2
2
5
.52 (d, 4H, J = 16.5 Hz, CH
2
–N), 3.71 (d, 4H, J = 16.5 Hz, CH
2
–N).
1
3
C NMR (CDCl
31.5, 129.6, 129.3, 128.0, 85.6, 36.5. MS (ESI): [M + Na] = 580.99
3
) d: 185.4 (CQO), 157.4 (N–CQO), 141.7, 136.1,
+
1
+
À1
and [M + H] = 559.02. IR (neat, cm ): n~ = 1727 (CQO amide),
1
5
654 (CQO quinone), 1287 (C–N). HRMS for C32
81.14316; found: 581.14314.
Compound 1
22 6 4
H O N Na calcd:
4
(a) M. Hardouin-Lerouge, P. Hudhomme and M. Sall ´e , Chem.
Soc. Rev., 2011, 40, 30; (b) J. Leblond and A. Petitjean, Chem-
PhysChem, 2011, 12, 1043; (c) E. M. P ´e rez and N. Mart ´ı n,
Chem. Soc. Rev., 2008, 37, 1512.
Method A. To a solution of compound 5a (100 mg, 0.18 mmol)
in anhydrous THF (10 mL) were successively added a solution
of 2,3-bis(bromomethyl)TTF 6 (300 mg, 0.32 mmol) in anhydrous
THF (10 mL), 18-crown-6 (569 mg, 2.15 mmol) (freshly recrystal-
5
6
C.-W. Chen and H. W. Whitlock Jr., J. Am. Chem. Soc., 1978,
1
00, 4921.
(a) S. C. Zimmerman and C. M. VanZyl, J. Am. Chem. Soc.,
987, 109, 7894; (b) S. C. Zimmerman, C. M. VanZyl and
3
lized in CH CN), anhydrous KI (95 mg, 0.58 mmol). The reaction
1
mixture was stirred for 24 h at room temperature under a nitrogen
atmosphere. After addition of EtOAc, the solvent was partially
concentrated under vacuum. The residue was purified by
chromatography on silica gel (eluents CH Cl , then CH Cl /
EtOAc 95/5 then CH
pound 1b as a green powder in 20% yield. Compound 1 was
recrystallized in a CH Cl –pentane mixture of solvents.
G. S. Hamilton, J. Am. Chem. Soc., 1989, 111, 1373; (c) S. C.
Zimmerman, M. Mrksich and M. Baloga, J. Am. Chem. Soc.,
1989, 111, 8528; (d) S. C. Zimmerman, Top. Curr. Chem.,
1993, 165, 71; (e) S. C. Zimmerman, Bioorg. Chem. Front.,
1991, 2, 33.
2
2
2
2
2 2
Cl /EtOAc 90/10) affording 75 mg com-
7
(a) F.-G. Kl ¨a rner, U. Burkert, M. Kamieth, R. Boese and
J. Benet-Buchholz, Chem. – Eur. J., 1999, 5, 1700; (b) F.-G.
Kl ¨a rner, J. Panitzky, D. Bl ¨a ser and R. Boese, Tetrahedron,
2001, 57, 3673; (c) F.-G. Kl ¨a rner and B. Kahlert, Acc. Chem.
Res., 2003, 36, 919; (d) F.-G. Kl ¨a rner, B. Kahlert, R. Boese,
D. Bl ¨a ser, A. Juris and F. Marchioni, Chem. – Eur. J., 2005,
11, 3363; (e) F. Marchioni, A. Juris, M. Lobert, U. P.
Seelbach, B. Kahlert and F.-G. Kl ¨a rner, New J. Chem., 2005,
29, 780; ( f ) F.-G. Kl ¨a rner, B. Kahlert, A. Nellesen, J. Zienau,
C. Ochsenfeld and T. Schrader, J. Am. Chem. Soc., 2006,
128, 4831; (g) G. Fukuhara, S. Madenci, J. Polkowska,
F. Bastkowski, F.-G. Kl ¨a rner, Y. Origane, M. Kaneda,
T. Mori, T. Wada and Y. Inoue, Chem. – Eur. J., 2007,
13, 2473.
2
2
Method B. 1-Butyl-3-methylimidazolium iodide (BMI-I)
(750 mg, 2.8 mmol) was placed in a round bottom flask under
an argon atmosphere. Compound 5 (100 mg, 0.18 mmol) and
,3-bis(bromomethyl)TTF 6 (340 mg, 0.36 mmol) were added,
2
and the solution was stirred at 60 1C for 72 h. After addition of
CH Cl , the organic layer was washed with brine, dried over
MgSO , and the solvent was removed under vacuum. The
residue was purified by using silica gel column chromato-
2
2
4
graphy (eluent: CH
2
Cl
) d: 7.90 (s, 4H, Harom), 7.63 (m, 16H, Harom),
.42–7.09 (m, 34H, Harom), 5.78 (s, 4H, Hhydroquinone), 5.62
2
) to afford compound 1 (80 mg, 21%).
1
2 2
H NMR (CD Cl
7
2
2
(d, 4H, J = 16.5 Hz, CH
2
–N), 3.72 (d, 4H, J = 16.5 Hz, CH
). C NMR (CD Cl ) d: 182.3 (CQOquinone),
2
–N),
8 P. Batail, Molecular Conductors (Thematic issue), Chem.
Rev., 2004, 104(11), 4887.
9 D. Canevet, M. Sall ´e , G. Zhang, D. Zhang and D. Zhu, Chem.
Commun., 2009, 2245.
1
3
1
1
1
1
2
.09 (s, 36H, CH
3
2
2
57.6 (CQOglycoluril), 145.3, 144.3, 144.1, 135.8, 132.5, 132.4,
32.3, 130.5, 129.8, 129.6, 129.5, 128.4, 128.2, 119.5, 116.4,
15.9, 107.0, 85.8, 36.7, 26.7, 19.7. MS: (MALDI-TOF, dithranol): 10 (a) J. L. Segura and N. Mart ´ı n, Angew. Chem., Int. Ed., 2001,
+
À1
126 (M ). IR (neat, cm ): n~ = 1719 (CQO ester), 1662 (CQO
40, 1372; (b) TTF Chemistry. Fundamentals and applications of
tetrathiafulvalene, ed. J. Yamada and T. Sugimoto, Springer
Verlag, 2004.
amide), 1258 (C–N), 1017 (C–O). HRMS for C120
calcd: 2149.43309; found: 2149.42240.
102 4 10 8 4
H N O S Si Na:
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014
New J. Chem.

View Article Online
Paper
NJC
11 C. M. Davis, J. M. Lim, K. R. Larsen, D. S. Kim, Y. M. Sung, 23 (a) C. Boulle, J.-M. Rabreau, P. Hudhomme, M. Cariou,
D. M. Lyons, V. M. Lynch, K. A. Nielsen, J. O. Jeppesen,
D. Kim, J. S. Park and J. L. Sessler, J. Am. Chem. Soc., 2014,
M. Jubault, A. Gorgues, J. Orduna and J. Gar ´ı n, Tetrahedron
Lett., 1997, 38, 3909; (b) P. Hudhomme, C. Boulle, J.-M.
Rabreau, M. Cariou, M. Jubault and A. Gorgues, Synth. Met.,
1998, 94, 73; (c) D. Kreher, S.-G. Liu, M. Cariou, P. Hudhomme,
A. Gorgues, M. Mas, J. Veciana and C. Rovira, Tetrahedron Lett.,
2001, 42, 3447; (d) S.-G. Liu, D. Kreher, P. Hudhomme,
E. Levillain, M. Cariou, J. Delaunay, A. Gorgues, J. Vidal-
Gancedo, J. Veciana and C. Rovira, Tetrahedron Lett., 2001,
42, 3717; (e) D. Kreher, M. Cariou, S.-G. Liu, E. Levillain,
J. Veciana, C. Rovira, A. Gorgues and P. Hudhomme,
J. Mater. Chem., 2002, 12, 2137; ( f ) A. Gorgues,
P. Hudhomme and M. Sall ´e , Chem. Rev., 2004, 104, 5151;
(g) P. Hudhomme, C. R. Chim., 2006, 9, 881.
136, 10410.
1
1
1
2 T. Poulsen, K. A. Nielsen, A. D. Bond and J. O. Jeppesen,
Org. Lett., 2007, 9, 5485.
3 M. H. D u¨ ker, H. Sch ¨a fer, M. Zeller and V. A. Azov, J. Org.
Chem., 2013, 78, 4905.
4 (a) V. A. Azov, R. G o´ mez and J. Stelten, Tetrahedron, 2008,
6
4, 1909; (b) M. Skibi n´ ski, R. G o´ mez, E. Lork and V. A. Azov,
Tetrahedron, 2009, 65, 10348.
1
5 (a) R. P. Sijbesma, S. S. Wijmenga and R. J. M. Nolte, J. Am.
Chem. Soc., 1992, 114, 9807; (b) R. P. Sijbesma, A. P. M.
Kentgens, E. T. G. Lutz, J. H. van der Maas and R. J. M.
Nolte, J. Am. Chem. Soc., 1993, 115, 8999; (c) R. P. Sijbesma 24 (a) C. Boulle, O. Desmars, N. Gautier, P. Hudhomme,
and R. J. M. Nolte, Top. Curr. Chem., 1995, 175, 25;
d) J. N. H. Reek, J. A. A. W. Elemans and R. J. M. Nolte,
J. Org. Chem., 1997, 62, 2234; (e) P. Polavarapu, H. Melander,
M. Cariou and A. Gorgues, Chem. Commun., 1998, 2197;
(b) N. Gautier, N. Mercier, A. Riou, A. Gorgues and
P. Hudhomme, Tetrahedron Lett., 1999, 40, 5997.
(
V. Langer, A. Gogoll and H. Grennberg, New J. Chem., 2008, 25 A. D. Thomas and L. L. Miller, J. Org. Chem., 1986, 51, 4160.
2, 643; ( f ) N. She, M. Gao, L. Cao, A. Wu and L. Isaacs, Org. 26 C. P. B ´e nard, Z. Geng, M. A. Heuft, K. VanCrey and
3
Lett., 2009, 11, 2603; (g) S. Ghosh, A. Wu, J. C. Fettinger,
P. Y. Zavalij and L. Isaacs, J. Org. Chem., 2008, 73, 5915.
6 (a) P.-N. Cheng, P.-T. Chiang and S.-H. Chiu, Chem. Commun.,
A. G. Fallis, J. Org. Chem., 2007, 72, 7229.
27 N. Gautier, F. Dumur, V. Lloveras, J. Vidal-Gancedo,
J. Veciana, C. Rovira and P. Hudhomme, Angew. Chem.,
Int. Ed., 2003, 42, 2765.
1
2005, 1285; (b) P.-T. Chiang, P.-N. Cheng, C.-F. Lin, Y.-H. Liu,
C.-C. Lai, S.-M. Peng and S.-H. Chiu, Chem. – Eur. J., 2006, 28 (a) P. D. Beer, P. A. Gale and G. Z. Chen, Coord. Chem. Rev.,
1
2, 865.
1999, 185–186, 3; (b) J. S. Park, F. Le Derf, C. M. Bejger,
V. M. Lynch, J. L. Sessler, K. A. Nielsen, C. Johnsen and
J. O. Jeppesen, Chem. – Eur. J., 2010, 16, 848.
1
1
7 Z.-G. Wang, B.-H. Zhou, Y.-F. Chen, G.-D. Yin, Y.-T. Li,
A.-X. Wu and L. Isaacs, J. Org. Chem., 2006, 71, 4502.
8 J. W. H. Smeets, R. P. Sijbesma, L. van Dalen, A. L. Spek, 29 S. Goeb, D. Canevet and M. Sall ´e , in Organic Synthesis and
W. J. J. Smeets and R. J. M. Nolte, J. Org. Chem., 1989,
4, 3710.
Molecular Engineering, ed. M. O. Nielsen, Wiley, 2013, ch. 8,
p. 213.
5
19 (a) A. R. Butler and I. Hussain, J. Chem. Soc., Perkin Trans. 2, 30 A. Jain, K. V. Rao, U. Mogera, A. A. Sagade and S. J. George,
1981, 310; (b) R. P. Sijbesma, W. P. Bosman and R. J. M.
Chem. – Eur. J., 2011, 17, 12355.
Nolte, J. Chem. Soc., Chem. Commun., 1991, 885.
0 (a) D. Walker and J. D. Hiebert, Chem. Rev., 1967, 67, 153;
31 V. Khodorkovsky, L. Shapiro, P. Krief, A. Shames, G. Mabon,
A. Gorgues and M. Giffard, Chem. Commun., 2001, 2736.
2
(
b) F. Dumur, N. Gautier, N. Gallego-Planas, Y. -Sahin, 32 J. Gao, E. T. Niles and J. K. Grey, J. Phys. Chem. Lett., 2013,
E. Levillain, N. Mercier, P. Hudhomme, M. Masino, 4, 2953.
A. Girlando, V. Lloveras, J. Vidal-Gancedo, J. Veciana and 33 (a) H. Hirose, J. Inclusion Phenom. Macrocyclic Chem., 2001,
C. Rovira, J. Org. Chem., 2004, 69, 2164.
1 J. Baffreau, F. Dumur and P. Hudhomme, Org. Lett., 2006,
39, 193; (b) H. Hirose, in Analytical methods in supramolecular
chemistry, ed. C. Schalley, Wiley, 2007, ch. 2, p. 17;
(c) P. Thordarson, Chem. Soc. Rev., 2011, 40, 1305.
2
2
8, 1307.
2 P. Hudhomme, S.-G. Liu, D. Kreher, M. Cariou and 34 S. Bivaud, J.-Y. Balandier, M. Chas, M. Allain, S. Goeb and
A. Gorgues, Tetrahedron Lett., 1999, 40, 2927.
M. Sall ´e , J. Am. Chem. Soc., 2012, 134, 11968.
New J. Chem.
This journal is © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2014