Synthetic routes to large tripodal organic receptors and the structural characterisation of intermediates

Article abstract of DOI:10.1016/j.tet.2015.12.048

This contribution explores synthetic routes adopted and optimized for the preparation of three new hexatopic tripodal organic ligands designed for Ln(III) complexation. In these ligands, three strands bearing two pyridyldicarbonyl binding moieties are anchored with a small aliphatic triamine. The described synthesis is not straightforward and depends on the nature of the spacer between coordinating moieties. In addition to the characterisation of targeted ligands, the structure of ditopic intermediates is assessed by X-ray crystallography and discussed with respect to the spacer nature.

Full text of DOI:10.1016/j.tet.2015.12.048

Tetrahedron 72 (2016) 928e935
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Synthetic routes to large tripodal organic receptors and the
structural characterisation of intermediates
a
a
b
a, ,
*
€
ꢀ
Soumaila Zebret , Eliane Vogele , Celine Besnard , Josef Hamacek
y
a Department of Inorganic and Analytical Chemistry, University of Geneva, 30 quai Ernest-Ansermet, 1211 Geneva 4, Switzerland
b Laboratory of Crystallography, University of Geneva, 24 quai Ernest-Ansermet, 1211 Geneva 4, Switzerland
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 2 July 2015
Received in revised form 17 December 2015
Accepted 22 December 2015
Available online 24 December 2015
This contribution explores synthetic routes adopted and optimized for the preparation of three new
hexatopic tripodal organic ligands designed for Ln(III) complexation. In these ligands, three strands
bearing two pyridyldicarbonyl binding moieties are anchored with a small aliphatic triamine. The de-
scribed synthesis is not straightforward and depends on the nature of the spacer between coordinating
moieties. In addition to the characterisation of targeted ligands, the structure of ditopic intermediates is
assessed by X-ray crystallography and discussed with respect to the spacer nature.
Keywords:
Ó 2015 Elsevier Ltd. All rights reserved.
Multistep synthesis
Hexatopic ligands
X-ray crystal structure
1. Introduction
tetranuclear complexes.3e5 The preparation of unsymmetrical tri-
podal ligands is more complex and less efficient, since the attach-
The preparation of sophisticated supramolecular compounds
usually requires well designed polytopic ligands, which encode
chemical informations for predictable self-assembly processes.1
The synthesis of targeted organic receptors may become a time-
demanding process and several synthetic steps are usually re-
quired.2 The choice of a synthetic strategy is governed by its fea-
sibility and the obtained yield in each synthetic step.
Since several years we are interested in designing new tripodal
receptors for complexing Ln(III) cations. These ligands possess
three strands attached to a suitable anchoring molecule, i.e., a tri-
amine. Each strand bears a tridentate coordination moiety specially
designed for complexing Ln(III). Playing with the nature of co-
ordination moieties and with the size and chemical structure of the
anchor allows a fine tuning of the receptor for targeted assemblies.
The synthesis of such symmetrical ligands (C3v) is carried out by
a successive coupling of building blocs to the central core, which
reminds the synthesis of dendrimers. Simple symmetrical tripods
(i.e., L1,3 L2,4 see Scheme 1) can be thus synthesised by the coupling
of selected coordinating moieties in one step. A relatively high
symmetry of tripodal ligands is often maintained in related su-
pramolecular systems, as it is shown for the assembly of tetrahedral
ment of different coordinating strands must be carried out at least
in two steps. This is the case of an unsymmetrical tripodal ligand L3,
which have been designed and used for assembling pentanuclear
edifices (see Scheme 1).6
In this contribution, we report on synthetic routes adopted for
preparing hexatopic tripodal ligands. Three symmetrical organic
receptors L4eL6 (see Scheme 2), where each strand bears two
coordinating moieties, differ in the nature of the spacer between
pyridyldicarbonyl coordination moieties. Our interest is also fo-
cused on the characterisation of ditopic linear by-products (1es, 2es
and 3es) by X-ray crystallography. Their analysis provides structural
information for better understanding intra- and intermolecular
interactions occurring within synthesised polytopic receptors.
2. Results and discussion
Ligand design. The targeted hexatopic C3v symmetrical re-
ceptors consist of three ditopic strands attached to the trifunctional
central anchor 1,1,1-tris(aminomethyl)ethane (TAME). Each strand
is composed of two identical coordination pyridyldicarbonyl moi-
eties connected to a spacer X. The nature of this spacer may play
a crucial role in the assembly of the expected supramolecular
complex especially with respect to its length and rigidity. We have
identified three potentially suitable spacers having different
structural properties. All spacers X are commercially available as
diamino derivatives (NH2-X-NH2, Y¼1e3), which allows their
convenient insertion between coordination moieties by forming
* Corresponding author. E-mail address: josef.hamacek@cnrs-orleans.fr
(J. Hamacek).
y
ꢀ
Current address: CBM e CNRS Orleans, Rue Charles
Sadron, 45071 Orleans Cedex 2, France.
http://dx.doi.org/10.1016/j.tet.2015.12.048
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

S. Zebret et al. / Tetrahedron 72 (2016) 928e935
929
O
HN
N
H
N
N
N
O
HN
HN
O
R
N
O
N
NH
O
O
3
HN
O
O
N
L1: R = -N(C2H5)2
L2: R = -OCH3
L3
O
N
N
O
Scheme 1. Structure of ligands L1eL3.
detailed below. All synthesised tripodal ligands are characterized
by NMR spectroscopy confirming their expected average C3v
symmetry.
Synthesis of L4. The ligand L4 is designed with a flexible propyl
spacer. Initially, the synthetic strategy A was adopted. The key in-
termediate 1b can be synthesized by coupling of 1a with 5. The
monoamine precursor 1a is obtained in a very good yield of 69%
from the coupling reaction between 4 and 1 (Scheme 3). Alterna-
tively, the precursor 1b is also prepared by coupling of 4 and 1e,
which is previously prepared by coupling 5 and 1 (Scheme 4).
Advantageously, the latter path consumes less of 4, whose syn-
thesis is more time-consuming. Another way for preparing 1b is
a one pot reaction according to Scheme 5. Owing to similar struc-
tural and reactivity properties of 4 and 5, this reaction theoretically
results in a statistical mixture, which consists of 50% of hetero-
substituted diamine 1b and 25% of each homosubstituted diamine
by-product 1es and 1am, respectively.
The hydrolysis of the ester 1b provides the monoacid 1c.
However, the final coupling of 1c with TAME (6) using CDI/THF does
not give the desired tripodal ligand L4 despite the use of different
coupling agents (DMAP, DCC). Apparently, a possible folding of the
ditopic intermediate 1c decreases its availability for the nucleo-
philic attack of the triamine and the desired product couldn’t be
identified in the mixture.2 Consequently, we have switched to the
strategy B, where the coupling with the triacid 8 also works with
a sufficient yield.4 The compound 8 is then coupled with the pre-
cursor 1a providing the ligand L4, which is then purified (yield:
46%) and characterised by its NMR spectrum showing 18 proton
signals (Fig. S1).
Scheme 2. Structure of targeted ligands L4eL6.
amide bonds. In the serie (propyl, dimethylphenyl, diphenylme-
than), the rigidity and length of the spacer are increasing. The
terminal carboxamide moieties are identical for all ligands and
ensure a reasonable solubility in view of further complexation
reactions.
General synthetic procedures. The retrosynthetic analysis of
the ligand structure (L4eL6) suggests two possible synthetic
routes, where the coupling of amine precursors with carboxylates
alternates with the hydrolysis of protected intermediates. The
strategy A (Scheme 3) consists of the initial preparation of ditopic
moieties Yb by condensation of carboxylate precursors (4, 5) and
diamino derivatives 1e3. A subsequent coupling of the ditopic in-
termediates Yc with the triamine anchor TAME (6) provides the
desired ligands L4eL6. The second route B (Scheme 3) consists of
the initial coupling of three binding moieties 5 with 6. The obtained
tripodal intermediate 8 is then coupled with unsymmetrical
amines Ya, where one binding moiety is already attached to the
spacer. These monoamine precursors are prefered over diamines Y
for avoiding the formation of undesired polymeric products. It is
worth noting that both routes have the same number of reaction
steps starting with the same compounds. The preparation of
monosubstituted diamines Ya is common for both routes. The
synthetic routes adapted for each hexatopic ligand L4eL6 are
Synthesis of L5. The strategy A based on the preparation of the
monoamine precursor 2a was initially attempted. However, the
diamine 2 is badly soluble in aprotic organic solvents (i.e., CH2Cl2,
Scheme 3. General scheme of the ligand synthesis with two main routes A and B. Conditions: (i) SOCl2/DMF/CH2Cl2, Et3N/CH2Cl2; or CDI/THF. (ii) a) KOH/MeOH/CH2Cl2; b) HCl.

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S. Zebret et al. / Tetrahedron 72 (2016) 928e935
Scheme 4. Synthesis of 1b via the monosubstituted precursors 1e.
toluene, THF) suitable for coupling reactions. Consequently, a more
soluble monosubstituted diamine reacts preferentially with the
activated acid 4 in the mixture and the disubstituted symmetrical
compound 2am is formed in a high yield. Taking this into account,
the disubstituted diamine 2b was prepared by the one pot reaction
ideally providing a statistical mixture of the disubstituted diamines
2b, 2es and 2am (Scheme 5). The experimental yields were 32%,
15% and 15%, respectively, which agrees well with the expected
ratio. The hydrolysis of the ester 2b provides monoacid 2c suitable
for coupling with TAME. In this case, the final coupling using CDI in
THF was successful and the ligand L5 was obtained in a moderate
total yield after purification on the chromatographic column (the
1H NMR spectrum in Fig. S2). The unavailability of monosubstituted
2a automatically disables the synthetic route B.
Synthesis of L6. First synthetic attempts for preparing L6 fol-
lowed the strategy A in Scheme 3. The monoamine intermediate 3a
was prepared accordingly,6 but the yield of the disubstituted
symmetrical by-product 3am was significant, again for solubility
reasons. Therefore, an alternative one pot statistical synthesis of 3b
was adopted for simultaneously reacting 4 and 5 with 3 (Scheme 5).
The desired product 3b was isolated by column chromatography in
a relatively good yield (33%) together with the by-products 3es and
3am (13% of each). The obtained yields roughly match the expected
ratio with an apparent advantage for dissymmetrical precursor 3b.
The subsequent hydrolysis of terminal ester groups in 3b led to the
acid 3c. However, the final coupling of 3c with triamine 6 was not
successful despite several attempts with different coupling agents
(SOCl2, C2O2Cl2 and N,N0-carbonyldiimidazole (CDI)). Therefore, we
have resorted to the synthetic strategy B. The coupling of the triacid
intermediate 8 with the unsymmetrical amine 3a proceeds without
difficulties and the targeted ligand L6 is obtained after purification
on a chromatographic column with the overall yield of 18% (the 1H
NMR spectrum in Fig. S3).
the crystal structure of the prepared tripodal ligands L4eL6.
However, all crystallization attempts were unsuccessful. Despite
this, their molecular structure can be reasonably estimated by
combining the crystal structure of the precursor 74 and the struc-
ture of ditopic binding strands containing two pyridyldicarbonyl
motifs linked with the spacer of interest. Indeed, the crystals suit-
able for X-ray diffraction studies were easily obtained for all diester
byproducts (1es, 2es and 3es) by slow evaporation of their solutions
in CH2Cl2. The collected crystallographic data are summarized in
Table 1.
Crystal structure of 1es. X-ray crystallography reveals that 1es
in solid state interacts with one water molecule via four hydrogen
bonds. Two of them involve the carbonyl oxygen of esters
(d(O.HOw)¼2.92 Ǻ) and the others are formed with amide protons
(d(NH.Ow)¼2.96 Ǻ) (Fig. 1a, Table S1). These interactions are
similar to those observed in the structure of 74 and force the mol-
ecule to adopt a folded conformation, as it is seen in Fig. 1. The
asymmetric unit contains half of the molecule because of its loca-
tion on the crystallographic C2 axis (Fig. 1b). Except the central
carbon atom (C10) through which pass the C2 axis, all other atoms
in the asymmetric unit are very close to the plane P1 defined by six
atoms of the pyridine ring (Table S2, Table S3). The angle between
the two pyridine rings in 1es is about 36.4ꢀ. No other significant
intermolecular interactions like hydrogen bonds or
pep-in-
teractions are observed in the crystal packing shown in Figs. S4 and
S5.
Crystal structure of 2es. The unit cell of the crystal contains two
ligand molecules that are named 2esA and 2esB (Fig. 2, Fig. S6).
However, only half of each molecule is present in the asymmetric
unit, which reflects the conservation of their C2 axis. The angle
between the plane P1A (pyridine) and the plane P2A (central
phenyl ring) on 2esA (84.4(1)ꢀ) is very close to that on 2esB
(83.0(1)ꢀ) (see Table S5 and S6). The two pyridine rings of 2esA are
involved in
pep stacking interactions with the neighboring mol-
ecules 2esA in the crystal lattice to form a chain. The same in-
teractions are observed with 2esB (Fig. S7). The nonequivalence of
2esA and 2esB in the asymmetric unit is mainly caused by their
different interactions with water molecules. While 2esA forms two
hydrogen bonds (one as a donor with the amide hydrogen,
2.1. X-ray crystal structures of diester byproducts 1es, 2es and
3es
Since the spatial preorganization of binding sites is important
for a successful complexation of metal ions, we were interested in
Scheme 5. One pot synthesis of Yb, Yes and Yam.

S. Zebret et al. / Tetrahedron 72 (2016) 928e935
931
Table 1
Crystal data and structure refinement for 1es, 2es and 3es
1es
2es
3es
CCDC
1409099
1405430
1405428
Empirical formula
Formula weight
T/K
Wavelength (A)
Crystal system
Space group
C
19H22N4O7
C24H24N4O7
480.47
140.1(2)
0.71073
C29H28N4O8
560.55
200.0(2)
0.71073
Monoclinic
P21/c
418.23
200.0(2)
0.71073
Orthorhombic Triclinic
P21 21
ꢁ
2
P1
Unit cell dimensions
ꢁ
a/A
20.209(4)
4.4810(9)
10.366(2)
90
90
90
7.1169(12)
12.3873(17)
13.419(2)
92.635(13)
102.042(13)
103.697(12)
1118.4(3)
2
22.284(5)
13.300(3)
8.4500(17)
90
92.15(3)
90
2502.6(9)
4
1.488
ꢁ
b/A
ꢁ
c/A
ꢀ
ꢀ
a
b
g
/
/
ꢀ
/
3
ꢁ
Volume (A )
Z
938.7(3)
2
1.480
0.115
440
Density(g cmꢁ3
)
1.427
0.107
504
Absorption coefficient (mmꢁ1)
F(000)
0.110
1176
Theta range for data collection
Index ranges
6.109e29.99ꢀ 2.42e26.76ꢀ
1.78e26.5ꢀ
ꢁ26ꢂhꢂ27,
ꢁ16ꢂ kꢂ17,
ꢁ11ꢂlꢂ11
18574
ꢁ6ꢂhꢂ4,
ꢁ28ꢂkꢂ28,
ꢁ14ꢂlꢂ12
7806
ꢁ8ꢂhꢂ8,
ꢁ15ꢂkꢂ15,
ꢁ16ꢂlꢂ16
10534
Fig. 2. Illustration of different types of interactions between water molecules and two
forms of 2es (2esA and 2esB).
Reflections collected
Independent reflections
2699
2494
0.0329
4612
3863
0.0431
5186
4306
0.0283
Crystal structure of 3es. The X-ray crystal structure of
a needle-like crystal of 3es is shown in Fig. 3. The secondary
amide functions constrain the plans of each pyridine ring and the
phenyl neighbor to adopt a small deviation of 20.2ꢀ and 25.8ꢀ,
respectively. The deviation of 64.8ꢀ between the planes of two
phenyl rings of the spacer gives the overall V-shape to the
molecule (Table S7). These angular deviations are similar to those
observed for the dicarboxamide analogue 3am.6 With the pres-
ence of four aromatic planes in the molecule, it is reasonable to
obs. (I>2
s(I))
Rint
Refinement method
Data/restraints/parameters
GoF
Full-matrix least-squares on F2
3258/2/150
1.057
0.0417
4612/0/332
1.037
0.0529
5186/6/396
1.072
0.0524
R1
wR(F2)
0.0961
0.1045
0.0877
ꢁꢁ3
Largest diff. peak and hole (e.A ) 0.26 and ꢁ0.22 0.24 and ꢁ0.22 0.23 and ꢁ0.18
expect the presence of
pep stacking (Table S8). A view of the
crystal packing along the b axis gives an illusion of the existence
of these interactions (Fig. S11). However, a closer examination of
the crystal structure along the c axis shows that these plans are
d(NH.Ow)¼2.88 Ǻ) and one as an acceptor with the carbonyl ox-
ygen of the ester (d(O.HOw)¼2.93 Ǻ), 2esB forms only one (as an
acceptor with the amide carbonyl, d(O.HOw)¼2.84 Ǻ) (Table S4,
Fig. 2). In addition, the fourth hydrogen bond occurs between NH of
2esB and the carbonyl oxygen of 2esA (d(NH.O)¼3.09 Ǻ, Table S4).
This globally results in a two-dimensional network, where the
forms 2esA and 2esB are interconnected by hydrogen bonds
(Fig. S8). The above pep stacking interactions and hydrogen bonds
are thus responsible for the overall crystal packing (Figs. S9 and
S10).
offset relative to each other, which prevents
pep stacking in-
teractions (Fig. S12). In contrast with the crystal structure of
3am,6 each molecule of 3es forms hydrogen bonds with two
water molecules in proximity of binding sites (Fig. 3). The relative
orientations of amides and esters are similar to what has been
observed in the structure of 7.4 Each water molecule behaves
simultaneously as
a donor (to a carbonyl group, average
Fig. 1. ORTEP representations (30% ellipsoid) of the crystal structure of 1es: a) View along the a axis with the atom numbering. The formation of hydrogen bonds with the water
molecule is highlighted. b) View along the C2 axis. c) View along the b axis.

932
S. Zebret et al. / Tetrahedron 72 (2016) 928e935
Fig. 3. ORTEP representation (30% ellipsoid) of 3es in the crystal structure: a) Front view with the atom numbering. The formation of hydrogen bonds with a water molecule is
highlighted. b) Side view showing the V-shape.
d(O.HOw)¼2.82 Ǻ) and as an acceptor of hydrogen bonding
(a secondary amide, average d(NH.Ow)¼3.01 Ǻ) (Fig. 3a, Table
S9). Water molecules form also hydrogen bonds between them
to give rise to water chains filling hydrophilic canals within
crystals. In this way, the coordinating moieties of 3es are ori-
ented in opposite directions (Fig. S13) and the molecules con-
stitute a two dimensional array.
4. Experimental
4.1. Solvents and starting materials
These were purchased from Acros Organics, Fluka AG and Sig-
maeAldrich and used without further purification unless other-
wise stated. Dichloromethane was distilled over CaH2. THF was
purified on standard packed columns. The following compounds
were prepared according to published procedures: 4,7 5,7 6,8 7,4 3a,6
3b6 and 3c.6 Their 1H and 13C spectra were identical with those
reported in literature.
3. Conclusions
The synthesis of hexatopic tripodal ligands was successfully
achieved. Although the successive coupling of building blocks ap-
pears feasible, several difficulties are encountered during the syn-
thesis of monoamine precursors Xa, mostly due to different
solubilities of the used spacer. A statistical synthesis can be alter-
natively adopted despite a moderate yield. The second problematic
point is the coupling of ditopic strands with the triamine 6. For the
spacers 1 and 3, this step was unsuccessful and the route B was
adopted for the synthesis.
4.2. Spectroscopic and analytical measurements
Mono and two dimensional NMR spectra (1H, 13C, DEPT, COSY,
HSQC) were recorded on a high-field NMR spectrometer (400 MHz,
Bruker). Routine ESI-MS spectra were measured with a API 150EX
LC/MS system.
The crystal structures of ditopic diester byproducts 1ese3es
elucidate the organization of binding strands and serve as
structural models of large ligands L4eL6. It was shown that
important differences result from the nature of the spacer be-
tween binding sites. A flexible aliphatic spacer induces the
folding of binding moieties, while a more rigid aromatic spacer
significantly rigidifies the strand and predetermines a linear
preorganization of binding moieties with 2, and a bent confor-
mation with 3, respectively. In addition, the dicarbonylpyridine
moieties are oriented oppositely, which preserves a C2 symmetry
of the strand making it favorable for a helicoidal organization
when complexed with metal ions. In this context, the formation
of octanuclear helicates was recently evidenced for the reaction
of L6 with Eu(III).11
Concerning the position of carbonyl groups with respect to
the pyridine nitrogen atoms, all three examined strands adopt
trans conformations for central amides, while the terminal ester
carbonyls adopt cis conformations. Similar configurations were
previously observed for 7.4 Since the ligands L4eL6 bear only
amide groups, we can reasonably predict transetrans configura-
tions of all binding moieties. This consequently implies the ro-
tation about the CpyeCO bond during complexation reactions,
which usually contributes to a decrease of overall reaction rates
with metal ions.
4.3. Synthesis of tri{N-carbamoyl-[6-(carboxy)pyridine-2]
methyl}ethyl (8)
A solution of KOH (3 equiv) in a minimum of MeOH was added
to a solution of 7 (353 mg, 0.58 mmol) in 10 ml of toluene. The
mixture was stirred for 14 h at room temperature under N2 at-
mosphere. A white precipitate was filtered and washed with
CH2Cl2. The residual solid was dissolved in water (20 ml), filtered,
and the solution was acidified to pH¼2 with HCl (2M). The pre-
cipitate was filtered and dried in vacuum to give 227 mg
(0.33 mmol) of the product (69% yield).
8: 1H NMR (D2O/MeOD):
d
(ppm)¼8.11 (d, 3H, CH), 8.09 (d, 3H,
CH), 8.03 (t, 3H, CH) 3.50 (s, 6H, CH2); 1.04 (s, 3H, CH3). 13C NMR:
d
¼172.7, 168.0, 154.0, 149.5, 139.9, 127.7, 124.6, 45.1, 43.7, 19.7 ppm.
ESI-MS (CH2Cl2); m/z: calcd for [8þH]þ: 565.5; obs. 565.3.
4.4. Synthesis of 6-(N,N-diethylcarbamoyl)-N-(3-
aminopropyl)-pyridine-2-carboxamide (1a)
A solution of 1.02 g (4.85 mmol) of carboxamide 4 and 0.86 g
(1.1 equiv) of CDI in 40 ml of dry THF was refluxed for 4 h. The
mixture was cooled using an ice bath and added slowly to a solution
of 2 ml (23.7 mmol) of diamine 1 in 10 ml of THF. The mixture was

S. Zebret et al. / Tetrahedron 72 (2016) 928e935
933
stirred at room temperature overnight. The solvent was evaporated
amount of DMF (200
ml) in CH2Cl2 (50 ml) under N2 atmosphere for
and the residual oil was distributed between half-saturated
NaHCO3 and CH2Cl2. The aqueous phase was basified with satu-
rated NaOH to pH¼12 and extracted several times with CH2Cl2. The
latter organic phases were combined, dried and evaporated to
provide 938 mg of 1a (73% yield based on 4).
2.5 h. The solvent and the excess of SOCl2 were evaporated and the
residue was dried under vacuum for two hours. The solid was dis-
solved in dichloromethane (30 ml) at 0 ꢀC and added dropwise tothe
solution of diaminopropane 1 (375 ml, 4.5 mmol) in CH2Cl2 (25 ml)
with triethylamine (2 ml). The resulting solution was stirred over
one night at room temperature and then evaporated to dryness. The
residue was partitioned between dichloromethane (150 ml) and
saturated aq NaHCO3 (150 ml). The aqueous phase was further
extracted with CH2Cl2 (3ꢃ100 ml). The organic phase was dried with
Na2SO4, filtered and evaporated to dryness. The resulting crude
mixture was separated bycolumn chromatography (silica gel, 200 g;
CH2Cl2eMeOH, 1e2%). The isolated compounds were dried under
vacuum to yield 546 mg (26%) of 1b, 230 mg (12%) of 1es and 205 mg
(9%) of 1am.
1a: 1H NMR (CDCl3):
d
(ppm)¼8.22 (1H, dd, CH), 8.19 (1H, t, NH),
7.96 (1H, t, CH), 7.66 (1H, dd, CH), 3.60 (4H, m, CH2), 3.30 (2H, q,
CH2), 2.89 (2H, q, CH2), 1.87 (2H, q, CH2), 1.30 (3H, t, CH3), 1.19 (3H, t,
CH3). 13C NMR (CDCl3):
d¼167.7, 163.7, 153.6, 148.5, 138.5, 125.3,
122.6, 43.2, 40.0, 39.5, 35.4, 32.0, 14.4, 12.7. ESI-MS (CH2Cl2); m/z:
calcd for [1aþH]þ, 265.4; obs. 265.6.
4.5. Synthesis of 6-(methoxycarbonyl)-(3-aminopropyl)-pyri-
dine-2-carboxamide (1e)
1es: 1H NMR (CDCl3):
CH), 8.24 (dd, 2H, CH), 8.03 (t, 2H, CH), 4.06 (s, 6H, CH3), 3.63 (q, 4H,
CH2), 2.03 (m, 2H, CH2). 13C NMR (CDCl3):
d
(ppm)¼8.73 (t, 2H, NH), 8.43 (dd, 2H,
A solution of 0.5 g (2.76 mmol) of methylester 5 and 0.493 g
(1.1 equiv) of CDI in 25 ml of dry THF was refluxed for 3 h. The
mixture was cooled using an ice bath and added slowly to a cold
d
¼165.1, 163.9, 150.4,
146.4, 138.6, 127.2, 125.5, 53.0, 36.7, 29.3 ppm. ESI-MS (CH2Cl2); m/
solution of diamine 1 (144 ml, 8.3 mmol) in 5 ml THF. The mixture
z: calcd for [1esþH]þ: 401.4; obs. 401.6.
was then heated at reflux for three hours. The solvent was evapo-
rated and the residual oil was partitioned between half-saturated
NaHCO3 and CH2Cl2. The aqueous phase was basified with satu-
rated Na2CO3 and the monosubstituted 1e was extracted three
times with CH2Cl2. The organic phases were combined, dried and
evaporated to provide 480 mg (74%) of 1e.
1am: 1H NMR (CDCl3):
d
(ppm)¼8.24 (dd, 2H, CH), 8.17 (t, 2H,
NH), 7.97 (t, 2H, CH), 7.70 (dd, 2H, CH), 3.61 (m, 8H, CH2), 3.57 (m,
4H, CH2), 3.36 (q, 4H, CH2), 1.97 (m, 2H, CH2), 1.33 (t, 6H, CH3), 1.23
(t, 6H, CH3). 13C NMR (CDCl3):
d
¼167.8, 164.1, 153.7, 148.6, 138.5,
125.3, 122.7, 43.2, 40.1, 36.8, 30.0, 14.5, 12.8. ESI-MS (CH2Cl2); m/z:
calcd for [1amþH]þ: 483.6; obs. 483.6.
1e: 1H NMR (CDCl3):
8.22 (1H, d, CH), 8.01 (1H, t, CH), 4.02 (3H, s, CH3), 3.59 (2H, q, CH2),
2.84 (2H, t, CH2),1.80 (2H, m, CH2). 13C NMR (CDCl3):
d
(ppm)¼8.42 (1H, t, NH); 8.38 (1H, d, CH),
4.8. Synthesis of 6-{[(6-diethylcarbamoyl-pyridine-2-
carbamoyl)]-propylcarbamoyl}-2-carboxypyridine (1c)
d
¼165.3,164.0,
150.6, 146.5, 138.5, 127.3, 125.6, 52.9, 39.3, 35.5, 31.8. ESI-MS
(CH2Cl2); m/z: calcd for [1eþH]þ, 238.3; obs. 238.1.
A solution of KOH (525 mg, 1.2 mmol) in a minimum of MeOH
was added dropwise to a solution of 1b (68.7 mg) in 15 ml of
CH2Cl2. The mixture was stirred for 4 h at room temperature under
N2 atmosphere. 88 mg of KOH was then added and the mixture was
stirred for additional 30 min. 50 ml of water was then added to the
mixture. The organic phase was removed and the aqueous phase
was further extracted with CH2Cl2 (2ꢃ50 ml) The pH of aqueous
phase was adjusted to 2 with HCl. The product was extracted with
3ꢃ50 ml of CH2Cl2. The latter organic phase was dried over anhy-
drous Na2SO4, filtered and evaporated to dryness to provide 395 mg
of 1c (78% yield).
4.6. Synthesis of 6-{[(6-diethylcarbamoyl-pyridine-2-
carbamoyl)]-propylcarbamoyl}-2-methoxycarbonylpyridine
(1b)
The compound 5 (0.40 g, 2.2 mmol) was refluxed with SOCl2 and
a catalytical amount of DMF (20 ml) in CH2Cl2 (30 ml) for 1.5 h under
N2 atmosphere. The solvent and the excess of thionylchlorid were
evaporated, and the residue was dried under vacuum for two hours.
The solid was dissolved in dichloromethane (10 ml) and added
dropwise to the solution of the monoamine 1a (0.38 g, 1.5 mmol) in
CH2Cl2 (10 ml) with triethylamine (1 ml). The resulting solution was
stirred for one night at room temperature and then evaporated to
dryness. The residue was partitioned between dichloromethane
(250 ml) and saturated aq NH4Cl (250 ml). The aqueous phase was
further extracted with CH2Cl2 (2ꢃ100 ml). The organic phase was
dried (Na2SO4), filtered and evaporated to dryness. The product was
purified by column chromatography (silica gel, CH2Cl2/MeOH,
0e5%) to give w500 mg (1.1 mmol, 79%) of 1b. The precursor 1b can
also be prepared by coupling 1e with 4 using an analogous
procedure.
1c: 1H NMR (CDCl3):
d
(ppm)¼12.33 (sbroad, 1H, OH), 9.77 (t, 1H,
NH), 8.45 (dd, 1H, CH), 8.42 (dd, 2H, CH), 8.38 (t, 1H, NH), 8.37 (dd,
1H, CH), 8.14 (t, 1H, CH), 8.04 (t, 1H, CH), 7.70 (dd, 1H, CH), 3.74 (q,
2H, CH2), 3.58 (m, 4H, CH2), 3.28 (q, 2H, CH2), 1.94 (m, 2H, CH2), 1.32
(t, 3H, CH3),1.19 (t, 3H, CH3). 13C NMR (CDCl3):
d¼167.9,166.4,164.2,
162.1, 153.6, 150.5, 148.6, 146.5, 139.3, 138.6, 127.5, 125.6, 124.7,
122.8, 43.1, 40.2, 37.0, 36.9, 29.9, 14.5, 12.9. ESI-MS (CH2Cl2); m/z:
calcd for [1cþH]þ: 428.5; obs. 428.6.
4.9. Synthesis of 1,1,1-tris{N-carbamoyl-{6-[3-(6-
diethylcarbamoyl)pyridine-2-carbamoylpropyl]-pyridine-2}
aminomethyl}ethane (L4)
1b: 1H NMR (CDCl3):
d
(ppm)¼9.93 (t, 1H, NH), 8.54 (t, 1H, NH),
8.38 (dd, 1H, CH), 8.27 (dd, 2H, CH), 8.24 (dd, 1H, CH), 8.03 (t, 1H,
CH), 7.97 (t, 1H, CH), 7.70 (dd, 1H, CH), 4.06 (s, 3H, CH3), 3.59 (m, 6H,
CH2), 3.41 (q, 2H, CH2), 1.99 (m, 2H, CH2), 1.30 (t, 3H, CH3), 1.19 (t,
365 mg (0.64 mmol) of the acid 8 and 346 mg of CDI (2.13 mmol)
were dissolved in 50 ml of dry THF. The mixture was refluxed for
3 h, cooled and added dropwise to a solution of 1a (683 mg,
2.58 mmol) in 30 ml of THF. The mixture was refluxed overnight.
The solvent was evaporated and the solid was partitioned between
CH2Cl2 and saturated NaHCO3. The product is extracted with
CH2Cl2. The organic layers were combined and evaporated. The
product was purified by column chromatography (silica gel, 60 g;
CH2Cl2eMeOH, 0e5%) to give 402 mg (0.3 mmol, 46%) of L4.
3H, CH3). 13C NMR (CDCl3):
d¼167.8, 165.2, 164.1, 164.0, 153.7, 150.5,
148.7, 146.4, 138.6, 138.5, 127.4, 125.7, 125.3, 122.7, 53.0, 43.1, 40.0,
36.8, 36.7, 29.8, 14.4, 12.7. ESI-MS (CH2Cl2); m/z: calcd for [1bþH]þ:
441.5; obs. 442.5; calcd for [1bþ2H]2þ: 221.3; obs. 221.4.
4.7. One pot synthetic procedure for obtaining 1b, 1es and
1am
L4: 1H NMR (CDCl3):
NH); 8.35 (d, 3H, CH); 8.28 (d, 3H, CH); 8.20 (s, 3H, NH); 8.17 (d, 3H,
CH); 8.06 (t, 3H, CH); 7.93 (t, 3H, CH); 7.68 (d, 3H, CH); 3.66 (m, 18H,
d
(ppm)¼9.99 (sbroad, 3H, NH); 9.89 (s, 3H,
The compound 5 (882 mg, 4.9 mmol,1 equiv) and the compound
4 (1.08 g, 4.9 mmol) were refluxed with SOCl2 (8 ml) and a catalytical

934
S. Zebret et al. / Tetrahedron 72 (2016) 928e935
CH2); 3.59 (q, 6H, CH2); 3.31 (q, 6H, CH2), 1.96 (m, 6H, CH2); 1.30 (t,
filtered and evaporated in vacuum to obtain 2.01 g (4.1 mmol) of 2c
(96% yield).
9H, CH3); 1.19 (t, 9H, CH3); 1.00 (s, 3H, CH3). 13C NMR (CDCl3):
d
¼167.8, 164.3, 164.1, 153.8, 149.1, 148.4, 147.9, 139.2, 138.6, 125.4,
2c: 1H NMR (CDCl3):
d
(ppm)¼9.19 (t, 1H, NH), 8.45 (d, 1H, CH),
124.9, 124.1, 122.6, 43.2, 42.8, 42.6, 40.0, 36.6, 29.8, 29.7, 19.8, 14.5,
12.8 ppm.
8.34 (d, 1H, CH), 8.33 (t, 1H, NH), 8.16 (d, 1H, CH), 8.10 (t, 1H, CH),
7.94 (t, 1H, CH), 7.65 (d, 1H, CH), 7.08 (s, 4H, CH), 4.52 (d, 2H, CH2),
4.45 (d, 2H, CH2), 3.54 (q, 2H, CH2), 3.26 (q, 2H, CH2), 1.25 (t, 3H,
ESI-MS (CH3CN); m/z: calcd for [L4þH]þ: 1346.5; obs. 1345.9;
calcd for [L4 þ2H]2þ: 673.8, obs. 674.3; calcd for [L4þNa]þ: 1367.5;
obs. 1367.9.
CH3), 1.12 (t, 3H, CH3). 13C NMR (CDCl3):
d
¼167.9, 166.3, 163.9, 162.0,
153.8, 150.3, 148.7, 146.5, 139.1, 138.6, 137.6, 128.3, 127.5, 126.0,
125.6, 123.0, 43.4, 42.9, 42.2, 40.2, 14.4, 12.8. ESI-MS (CH2Cl2); m/z:
calcd for [2cþH]þ: 490.5; obs. 490.8; calcd for [2c2þH]þ: 980.0, obs.
979.7; calcd for [2cþNa]þ: 512.5; obs. 512.3; calcd for [2c2þNa]þ:
1002.0, obs. 1001.8.
4.10. Preparation of 6-{[(6-diethylcarbamoyl-pyridine-2-
ꢀ
methylcarbamoyl)]-benzylcarbamoyl}-2-
methoxycarbonylpyridine (2b)
The compound 4 (2.45 g, 11 mmol, 1 equiv) and the compound
5 (2.0 g, 11 mmol, 1 equiv) were refluxed with SOCl2 (7 ml) and
4.12. Synthesis of 1,1,1-tris{N-carbamoyl-{6-[4-(6-
diethylcarbamoyl-pyridine-2-carbamoylmethyl)-benzylcarba-
moyl]-pyridine-2}aminomethyl}ethane (L5)
a catalytical amount of DMF (60
ml) in 50 ml CH2Cl2 for 1.5 h
under N2 atmosphere. The solvent and the excess of thionyl-
chlorid were evaporated, and the residue was dried under vac-
uum. The solid was dissolved in dichloromethane (50 ml) at 0 ꢀC
and added dropwise to the solution of the diamine 2 (1.5 g) in
CH2Cl2 (30 ml) with triethylamine (2 ml). The resulting solution
was stirred over one night at room temperature and evaporated
to dryness. The residue was partitioned between dichloro-
methane and saturated aq NaHCO3. The aqueous phase was fur-
ther extracted with CH2Cl2 (3ꢃ100 ml). The organic phase was
dried (Na2SO4), filtered and evaporated to dryness. The resulting
crude mixture was separated by column chromatography (silica
gel, 300 g; CH2Cl2eMeOH, 0e2%). The isolated compounds were
dried under vacuum to yields 1.75 g (32%) of 2b. The compounds
2am and 2es were isolated with 15% yields.
The acid 2c (2.3 g, 4.7 mmol) was refluxed with CDI (838 mg,
5.17 mmol) in 100 ml of THF for 4 h under N2 atmosphere. The
mixture was cooled using an ice bath. A solution of TAME (157.4 mg,
1.34 mmol) in THF (10 ml) was then added dropwise. The mixture
was stirred at 60 ꢀC over one night and then evaporated to dryness.
The residue was partitioned between CH2Cl2 and saturated aq
NaHCO3. The aqueous phase was further extracted with CH2Cl2. The
organic phase was dried (Na2SO4) and evaporated to dryness. The
resulting crude mixture was purified by column chromatography
(silica gel, 200 g; CH2Cl2eMeOH, 0e6 %). The isolated fractions
were collected and dried under vacuum to give 1.18 g of L5 (58%).
L5: 1H NMR (CD3CN):
d
(ppm)¼9.64 (s, 3H, NH), 9.51 (t, 3H, NH),
8.52 (t, 3H, NH), 8.24 (d, 3H, CH), 8.11 (d, 3H, CH), 8.05 (t, 3H, CH),
7.90e8.05 (m, 6H, CH), 7.62 (d, 3H, CH), 7.24 (d, 6H, CH), 7.16 (d, 6H,
CH), 4.64 (d, 6H, CH2), 4.48 (d, 6H, CH2), 3.46 (q, 6H, CH2), 3.18 (q,
6H, CH2), 3.06 (slarge, 6H, CH2), 1.17 (t, 9H, CH3), 1.03 (t, 9H, CH3),
2b: 1H NMR (CD3CN):
d
(ppm)¼8.48 (t, 1H, NH), 8.40 (d, 1H, CH),
8.29 (d, 1H, CH), 8.25 (d, 1H, CH), 8.21 (t, 1H, NH), 8.04 (t, 1H, CH),
7.98 (t, 1H, CH), 7.7 (d, 1H, CH), 7.3e7.4 (m, 4H, CH Ar), 4.6e4.8 (2d,
4H, CH2), 3.57 (q, 2H, CH2), 3.27 (q, 2H, CH2), 1.63 (s, 3H, MeeO),
0.78 (s, 3H, CH3). 13C NMR (CD3CN):
d
¼167.5, 163.6, 163.5, 155.7,
1.28 (t, 3H, CH3), 1.12 (t, 3H, CH3). 13C NMR (CDCl3):
d
¼167.7, 165.0,
153.5,148.6, 148.4,147.8, 138.9, 138.5, 137.6, 137.1, 127.4, 127.2, 125.0,
124.6, 124.2, 122.3, 43.2, 42.9, 42.7, 42.1, 39.7, 19.4, 13.9, 12.4 ppm.
ESI-MS (CD3CN); m/z: calcd for [L5þH]þ: 1532.7; obs. 1532.2; calcd
for [L5þ2H]2þ: 766.9, obs. 766.8; calcd for [L5þHþNa]2þ: 777.9,
obs. 777.7; calcd for [L5þNa]þ: 1554.7; obs. 1554.2; calcd for
[L5þNa2]2þ: 788.9, obs. 789.2.
163.8, 163.5, 153.6, 150.1, 148.6, 146.7, 138.6, 138.5, 137.4, 128.2,
127.3, 125.6, 125.4, 122.8, 52.9, 43.2, 43.1, 40.0, 14.4, 12.7. ESI-MS
(CH2Cl2); m/z: calcd for [2bþH]þ: 504.6; obs. 504.6; calcd for
[2b2þH]þ: 1008.1, obs. 1007.8; calcd for [2bþNa]þ: 526.7; obs.
526.5; calcd for [2b2þNa]þ: 1030.12, obs. 1029.8.
2am: 1H NMR (CDCl3):
d
(ppm)¼8.60 (t, 2H, NH), 8.27 (dd, 2H,
CH), 8.12 (dd, 2H, CH), 8.04 (t, 2H, CH), 7.32 (s, 4H, CH), 4.60 (d, 4H,
CH2), 3.53 (q, 2H, CH2), 3.23 (q, 2H, CH2), 1.22 (t, 3H, CH3), 1.07 (t,
4.13. Preparation of 1-[(6-diethylcarbamoyl)pyridine-2-
carbamoylphenylmethyl]benzene-4-[6-methoxycarbonyl)pyr-
idine-2-carbamoyl] (3b), bis[(6-methoxycarbonyl)pyridine-2-
carbamoylphenyl]methane (3es) and bis[(6-diethylcarbamoyl)
pyridine-2-carbamoylphenyl]methane (3am)
3H, CH3). 13C NMR (CDCl3):
d
¼167.8, 163.8, 153.8, 148.7, 138.6, 137.5,
128.2, 125.6, 123.0, 43.3, 43.2, 40.2, 14.5, 12.9. ESI-MS: (CH2Cl2); m/
z: calcd for [2amþH]þ: 545.7; obs. 545.8.
2es: 1H NMR (CDCl3):
d
(ppm)¼8.59 (t, 2H, NH), 8.32 (dd, 2H,
CH), 8.22 (dd, 2H, CH), 8.11 (t, 2H, CH), 7.36 (s, 4H, CH), 4.61 (d, 4H,
CH2), 3.95 (s, 6H, CH3). 13C NMR (CDCl3):
d¼165.0, 163.5, 150.1,
The compound 4 (1.2 g, 1 equiv) and the compound 5 (1.0 g,
5.5 mmol, 1 equiv) were refluxed with SOCl2 (3.6 ml) and a cata-
lytical amount of DMF (100 ml) in 120 ml CH2Cl2 for 1.5 h under N2
146.6, 138.6, 137.6, 128.2, 127.3, 125.6, 52.9, 43.2 ppm. ESI-MS
(CH2Cl2); m/z: calcd for [2esþH]þ: 462.5; obs. 463.5; calcd for
[2esþNa]þ: 485.5; obs. 485.5.
atmosphere. The solvent and the excess of thionylchloride was
evaporated, and the residue was dried under vacuum. The solid was
dissolved in dichloromethane (50 ml) at 0 ꢀC and added dropwise
to the solution of bis(4-aminophenyl)methan (4.9 mmol) in CH2Cl2
(15 ml) with triethylamine (2 ml). The resulting solution was stirred
for 16 h at room temperature and then evaporated to dryness. The
residue was partitioned between dichloromethane and half-
saturated aq NaHCO3. The aqueous phase was further extracted
with CH2Cl2 (3ꢃ100 ml). The organic phase was dried (Na2SO4) and
evaporated to dryness. The resulting crude mixture was separated
by column chromatography (silica gel, 200 g; CH2Cl2eMeOH,
0e1%). The isolated compounds were dried under vacuum to yield
33% of 3b, 13% of 3es, and 13% of 3am.
4.11. Synthesis of 6-(4-{[(6-diethylcarbamoyl-pyridine-2-
methylcarbamoyl)]}-benzylcarbamoyl)-2-carboxypyridine
(2c)
A solution of KOH (1 equiv) in a minimum of MeOH was added
dropwise to a solution of 2b (2.15 g, 4.27 mmol) in 50 ml of CH2Cl2.
The mixture was stirred for 14 h at room temperature under N2
atmosphere, and the solvent was then removed to dryness. The
residual solid was dissolved in water, filtered, and the solution was
acidified to pH¼2 with HCl conc. The aqueous phase was further
extracted with CH2Cl2. The organic phase was dried (Na2SO4),

S. Zebret et al. / Tetrahedron 72 (2016) 928e935
935
3b: 1H NMR (CDCl3):
NH), 8.11e8.33 (m, 6H, CH), 7.75e7.79 (m, 4H, CH), 7.26 (d, 2H, CH),
d
(ppm)¼10.32 (s, 1H, NH), 10.31 (s, 1H,
5. Single crystal structure determination
7.25 (d, 2H, CH), 3.96 (s, 2H, CH2), 3.50 (q, 2H, CH2), 3.25 (q, 2H,
Summary of crystal data, intensity measurements and structure
refinements for 1es, 2es and 3es are collected in Table 1. Cell di-
mensions and intensities were measured on a Stoe IPDS diffrac-
CH2), 1.12e1.22 (m, 9H, CH3). 13C NMR (CDCl3):
d¼167.7,165.0,161.4,
161.2, 153.5, 150.4, 148.6, 146.4, 139.0, 138.9, 137.6, 137.5, 135.7,
129.7, 129.6, 127.5, 125.7, 123.0, 120.5, 119.9, 52.9, 43.3, 41.0, 40.3,
14.7, 12.9. ESI-MS (CH3CN); m/z: calcd for [3bþHþ]þ: 566.6; obs.
566.5; calcd for [3b2þHþ]þ; 1132.2; obs. 1131.8.
tometer with graphite-monochromated Mo[K
a
]
radiation
ꢁ
(
l
¼0.71073 A). The structures were solved by direct methods
(SIR2004).9 All other calculations were performed with the
SHELX10 system and MERCURY programs. The atomic positions of
the hydrogen atoms were calculated. All non-hydrogen atoms were
refined with anisotropic displacement parameters. CCDC 1405428,
CCDC 1405430 and CCDC 1409099 contain the supplementary
crystallographic data. These data can be obtained free of charge
from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
3es: 1H NMR (CDCl3):
d
(ppm)¼10.03 (s, 2H, NH), 8.51 (dd, 2H,
CH), 8.29 (dd, 2H, CH), 8.08 (t, 2H, CH), 7.76 (d, 4H, CH), 7.25 (d, 4H,
CH), 4.07 (s, 6H, CH3), 4.02 (s, 2H, CH2). 13C NMR (CD3CN):
d¼165.0,
161.2, 150.3, 146.4, 138.8, 137.5, 135.6, 129.5, 127.4, 125.6, 120.4, 53.0,
40.9 ppm. ESI-MS (CH3CN); m/z: calcd for [3esþH]þ: 401.4; obs.
401.5.
3am: 1H NMR (CD3CN):
d
(ppm)¼9.89 (s, 2H, NH), 8.26 (d, 2H,
CH), 8.10 (t, 2H, CH), 7.73 (d, 4H, CH), 7.72 (d, 2H, CH), 7.29 (d, 4H,
CH), 3.99 (s, 2H, CH2), 3.58 (q, 4H, CH2), 3.32 (q, 4H, CH2), 1.28 (t, 6H,
CH3), 1.22 (t, 6H, CH3). 13C NMR (CD3CN):
d¼168.3, 162.6, 155.1,
Acknowledgements
149.6, 140.1, 138.7, 137.1, 130.1, 126.4, 123.3, 121.1, 43.9, 41.2, 40.6,
14.7, 13.1 ppm. ESI-MS (CH3CN); m/z: calcd for [3amþHþ]þ: 607.7;
obs. 607.5; calcd for [3amþNaþ]þ 629.7; obs. 629.5; calcd for
[3amþHþ]þ: 1213.9; obs. 1213.5.
Financial support from the University of Geneva and the Suisse
National Foundation (200020-126758) is gratefully acknowledged.
4.14. Preparation of 1,1,1-tris{N-carbamoyl-{6-[4-(6-
diethylcarbamoyl-pyridine-2-carbamoylphenyl-4-methyl)-
phenyl-4-carbamoyl]-pyridine-2}aminomethyl}ethane (L6)
Supplementary data
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2015.12.048.
The acid 8 (225 mg, 0.4 mmol) was refluxed with CDI (213 mg,
1.3 mmol) in 50 ml of THF for 4 h under N2 atmosphere. A solution
of 3a (802 mg, 2.0 mmol) in THF is then added dropwise. The
mixture was refluxed over one night and then evaporated to dry-
ness. The residue was partitioned between dichloromethane
(100 ml) and saturated aq NaHCO3 (100 ml). The aqueous phase
was further extracted with CH2Cl2 (3ꢃ100 ml). The organic phase
was dried (Na2SO4) and evaporated to dryness. The resulting crude
mixture was purified by column chromatography (silica gel, 30 g;
CH2Cl2eMeOH, 0e2%). The isolated product was dried under vac-
uum to give 122 mg of L6 (18%).
References and notes
1. Lehn, J.-M. In Supramolecular Chemistry; VCH, Weinheim: New York, Basel,
Cambridge, Tokyo, 1995.
2. Zeckert, K.; Hamacek, J.; Senegas, J.-M.; Dalla-Favera, N.; Floquet, S.; Bernar-
dinelli, G.; Piguet, C. Angew. Chem., Int. Ed. Engl. 2005, 44, 7954e7958.
3. (a) Hamacek, J.; Bernardinelli, G.; Filinchuk, Y. Eur. J. Inorg. Chem. 2008,
3419e3422; (b) Hamacek, J.; Besnard, C.; Penhouet, T.; Morgantini, P.-Y. Chem.
dEur. J. 2011, 17, 6753e6764.
4. Zebret, S.; Besnard, C.; Bernardinelli, G.; Hamacek, J. Eur. J. Inorg. Chem. 2012,
2409e2417.
L6: 1H NMR (CD3CN):
d
(ppm)¼10.49 (s, 3H, NH); 9.87 (s, 6H,
ꢀ
ꢀ
5. El Aroussi, B.; Guenee, L.; Pal, P.; Hamacek, J. Inorg. Chem. 2011, 50, 8588e8597.
6. El Aroussi, B.; Zebret, S.; Besnard, C.; Perrottet, P.; Hamacek, J. J. Am. Chem. Soc.
2011, 133, 10764e10767.
NH); 8.39 (dd, 3H, CH); 8.27 (dd, 3H, CH); 8.11 (d, 3H, CH); 8.07 (t,
3H, CH); 7.92 (t, 3H, CH); 7.73 (m, 15H, CH); 7.21 (d, 6H, CH); 7.15 (d,
6H, CH); 3.93 (s, 6H, CH2); 3.57 (q, 6H, CH2); 3.46 (s, 3H, CH2); 3.32
(q, 6H, CH2); 1.25 (m, 18H, CH3); 1.10 (s, 3H, CH3). 13C NMR (CD3CN):
ꢀ
ꢀ
7. Dalla Favera, N.; Guenee, L.; Bernardinelli, G.; Piguet, C. Dalton Trans. 2009,
7625e7638.
8. (a) Geue, R. J.; Searle, G. H. Aust. J. Chem. 1983, 36, 927e935; (b) Brown, K. N.;
Hockless, C. R.; Sargeson, A. M. Dalton Trans. 1999, 2171e2175.
9. Burla, M. C.; Caliandro, R.; Camalli, M.; Carrozzini, B.; Cascarano, G. L.; De Caro,
L.; Giacovazzo, C.; Polidori, G.; Spagna, R. J. Appl. Crystallogr. 2005, 38, 381e388.
10. Sheldrick, G. M. SHELXL97 Program for the Solution and Refinement of Crystal
d
(ppm)¼167.4, 161.4, 161.2, 153.4, 148.9, 148.4, 147.9, 138.9, 138.7,
137.5, 137.3, 135.6, 135.5, 129.1, 128.9, 125.4, 124.9, 122.6, 122.4,
121.4, 119.7, 42.9, 42.1, 40.5, 39.8, 29.3, 19.5, 14.1, 12.4. ESI-MS
(CD3CN); m/z: calc.for [L6þH]þ: 1718.9; obs. 1718.7; calcd for
[L6þ2H]2þ: 859.9; obs. 859.5.
€
Structures; University of Gottingen: Germany, 1997.
€
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