High-yield synthesis of potentially ditopic coordinating cryptands and their metal complexes

Article abstract of DOI:10.1016/j.tetlet.2013.04.074

Cryptands containing a tetradentate tris(aminoethyl)amine moiety have been prepared in high-yield via copper-catalyzed alkyne-azide cycloaddition followed by a templated 3+3 condensation. Silver and zinc complexes of the cryptands are reported. Weak interactions between a chloride anion and the cryptand suggest possible ditopic coordination.

Full text of DOI:10.1016/j.tetlet.2013.04.074

Tetrahedron Letters 54 (2013) 3363–3365
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
High-yield synthesis of potentially ditopic coordinating cryptands and
their metal complexes
Laura Chaloner a, Xavier Ottenwaelder a,
⇑
a Department of Chemistry and Biochemistry, Concordia University, 7141 Sherbrooke Street West, Montreal, Canada H4B 1R6
a r t i c l e i n f o
a b s t r a c t
Article history:
Cryptands containing a tetradentate tris(aminoethyl)amine moiety have been prepared in high-yield via
copper-catalyzed alkyne–azide cycloaddition followed by a templated 3+3 condensation. Silver and zinc
complexes of the cryptands are reported. Weak interactions between a chloride anion and the cryptand
suggest possible ditopic coordination.
Received 11 March 2013
Revised 12 April 2013
Accepted 15 April 2013
Available online 25 April 2013
Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved.
Keywords:
Cryptand
Supramolecular chemistry
Ditopic ligand
Templated macrocycle synthesis
Anion binding
Propelled by the importance of anions in environmental and
biomedical processes,1,2 anion recognition is now an important
branch of supramolecular chemistry.3,4 In order to efficiently and
selectively bind anions, ligands incorporate functionalities such
methylation to yield cryptand 6. The 1H NMR of cryptands 4, 5,
and 6 in CDCl3 indicate C3 symmetry in solution. Complete assign-
ment of 1H chemical shifts, was realized via COSY and NOESY
experiments (see Supplementary information).
as hydrogen bond donors,5,6 metal coordination sites,7
p-sys-
The [3+3] condensation was implemented under both template
and semi-dilute conditions. Templating with lanthanum(III) nitrate
proved to be an efficient procedure, with a 72% yield for the one-
pot, two-step 3?5 sequence, compared with 30% under nontem-
plated conditions. Different metal ions were tested as templating
agents. Cobalt(II) chloride, zinc(II) chloride, and silver(I) nitrate
were chosen as they form complexes with 5 (see below), but lan-
thanum(III) nitrate was by far the best templating agent. With zinc
and silver, yields of 30% were obtained, likely due to the difficulty
in purifying 5. Cobalt(II) chloride had a negative effect on the reac-
tion by inhibiting the formation of the cryptand completely. No
complexes were observed between lanthanum nitrate and 3, 4,
or 5 by ESI-MS in 1:1 methanol/dichloromethane, consistent with
a kinetic templating effect. The lanthanum ion likely coordinates
to tren, as previously reported,21,22 and this complex is poised to
react with trialdehyde 3. Once the cryptand is formed, the oxophil-
ic lanthanum(III) ion is easily removed during work-up with the
oxygen-rich EDTA ligand. In contrast, removal of cobalt, zinc, and
silver ions from the formed cryptand proved difficult as these ions
form stable complexes in the nitrogen-rich environment of 5.
X-ray diffraction analysis of single crystals of 6ÁEt2O indicate
that methylated cryptand 6 adopts an endo-endo conformation
(Fig. 1), as is customary with cryptands bearing tren moieties.23
The molecular structure of 6 has a C1 symmetry due to the anti
tems,8–10 or combinations thereof.11–13 Furthermore, anion encap-
sulation is particularly selective with cryptands due to the
geometric constraints imparted by their rigidity. Presented here
are the high-yielding syntheses of novel cryptands with two differ-
ent binding sites, one hard polyamine site and one soft tris(tria-
zole) site. As described recently,14–17 the polarized C–H bonds of
the triazoles are conducive to bind anions and thus impart the
cryptands with attributes to serve as a heteroditopic ligand for an-
ion recognition.
The macrobicyclic scaffold was prepared in two steps from 3-
(2-propyn-1-yloxy)benzaldehyde, 1, and tris(2-azidoethyl)amine,
2
(CAUTION),18 which syntheses were reported previously
(Scheme 1).19,20 The end caps of the cryptands were constructed
successively, first by copper-catalyzed azide-alkyne cycloaddition
(CuAAC) to yield 93% of 3, then by a [3+3] reversible condensation
with tris(2-aminoethyl)amine (tren) to yield triimine cryptand 4.
Though 4 can be isolated, a same-pot borohydride reduction was
preferred as it yielded larger quantities of cryptand 5. The amine
groups of 5 can be easily functionalized, as demonstrated by a
⇑
Corresponding author. Tel.: +1 514 848 2424x8934; fax: +1 514 848
2424x2868.
E-mail address: dr.x@concordia.ca (X. Ottenwaelder).
0040-4039/$ - see front matter Crown Copyright Ó 2013 Published by Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.04.074

3364
L. Chaloner, X. Ottenwaelder / Tetrahedron Letters 54 (2013) 3363–3365
CHO
(a)
N4
(b)
CHO
CHO
N1
N7
N1
N2
H
N3
N2
Ag1
Zn1
Cl1
O
O
N
O
N
O
N
N3
N3
(i)
N3
+
N
N11
O
N
N
N
N
N
N
N
2
1
Cl2
(ii)
3
N
N
N
R
R
N
R
N
N
N
N
O
N
(iii)
O
N
O
O
O
O
N
Figure 2. ORTEP representations at 50% thermal ellipsoid probability of: (a) the
cationic part of [5Ag](NO3)ÁCH3OH, and (b) [5ZnCl](Cl). The hydrogen atoms were
omitted for clarity. Selected bond lengths (Å) and angles (°) for [5Ag](NO3)ÁCH3OH:
Ag1–N1 = 2.506(5), Ag1–N2 = 2.398(5), Ag1–N3 = 2.385(4), Ag1–N4 = 2.370(5), N1–
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
Ag1–N2 = 74.85(15),
N1–Ag1–N3 = 74.99(15),
N1–Ag1–N2 = 75.29(15);
for
N
N
[5ZnCl](Cl): Zn1–N1 = 2.245(5), Zn1–N2 = 2.104(4), Zn1–N7 = 2.160(5), Zn1–
N11 = 2.110(4), Zn1–Cl1 = 2.2861(14).
R = H
R = Me 6
5
4
(iv)
between two triazole units, thus competing with coordination at
this site. The Ag atom sits in a distorted trigonal–pyramidal envi-
ronment composed of the nitrogen atoms of three tren moiety,
with the Ag sitting below the equatorial plane. The out-of-plane ef-
fect is commonly found in silver complexes with tren.29–36
Scheme 1. Synthesis of cryptands 4–6. Conditions: (i) CuSO4, NaAsc, t-BuOH:H2O
1:1, 24 h, 93%; (ii) tren, La(NO3)3, MeOH:THF 10:1, 48 h, 48%; (iii) NaBH4,
MeOH:THF 10:1, 3 h, 72% over 2 steps; (iv) CH2O, HCO2H, 24 h reflux, 80%.
The ditopic nature of cryptand 5 is revealed upon solid-state
characterization of its zinc(II) chloride complex. A mononuclear
complex of formula [5ZnCl](Cl)ÁH2O was obtained by mixing 5 with
zinc(II) chloride in hot methanol and letting the solution cool
down. Formation of the complex was confirmed in solution with
ESI-MS, the major peaks corresponding to the isotopic pattern of
[5ZnCl]+. Single crystals amenable to X-ray diffraction analysis
were grown by slow diffusion of diethyl ether into a methanol
solution of the compound. The complex crystallizes as [5ZnCl](Cl)
in the chiral P21 space group (Fig. 2).37 The cryptand adopts an
endo–endo conformation and has an overall C1 symmetry.
Akin to free ligand 6 and silver complex [5Ag]+, this structure re-
N2
H28A
C12
N6
N1
C13
N10
veals a weak C–HÁ Á Á
p interaction between two triazole units
(H40A on Fig. 3). The Zn atom adopts a trigonal–bipyramidal coor-
dination geometry within the tren moiety with the chloride (Cl1)
Figure 1. ORTEP representation at 50% thermal ellipsoid probability of 6ÁEt2O. The
co-crystallized diethyl ether and hydrogen atoms (except H28A) were omitted for
clarity.
H28A
conformation of the N1–C31–C32–N10 linkage while the other two
tren nitrogens (N2 and N6) adopt a syn conformation in relation to
N1 through their respective ethylene links. The only significant
H13A
H26A
intramolecular contact within the cryptand is a C–HÁ Á Á
p interac-
tion between two triazole units (H28AÁ Á ÁC12 = 2.684 and
H28AÁ Á ÁC13 = 2,792 Å, van der Waals radii: C, 1.70; H, 1.20 Å).
The coordination ability of cryptands 5 and 6 resides principally
in the multi-chelating tren moiety, as illustrated here with mono-
meric silver(I) and zinc(II) complexes of 5. Attempts to isolate
dinuclear complexes involving coordination to the triazole moie-
ties24,25 have yet to be successful. Addition of silver(I) nitrate to a
hot solution of 5 in methanol led to a crystalline precipitate after
cooling. The structure of this complex, [5Ag](NO3)ÁCH3OH, was
solved by X-ray diffraction (Fig. 2). The inner-sphere complex,
[5Ag]+, has a pseudo-C3 symmetry. The Ag atom is coordinated to
the tren moiety, despite the potential to coordinate with the tria-
zole groups, as shown in the literature.26–28 Two of the triazoles
Cl2
N4
H40A
H12A
Cl1
N3
Zn1
Figure 3. Zoom of the ORTEP representation (50% thermal ellipsoid probability) of
[5ZnCl](Cl). The hydrogen atoms were omitted for clarity except those involved in
weak contacts. Selected distances (Å): Cl2Á Á ÁH12A = 2.601, Cl2Á Á ÁH26A = 2.657,
Cl2Á Á ÁH13A = 2.728, Cl2Á Á ÁH28A = 2.893, H40AÁ Á ÁN3 = 2.614, H40AÁ Á ÁN4 = 2.774.
are facing each other, and a weak C–HÁ Á Á
p interaction exists

L. Chaloner, X. Ottenwaelder / Tetrahedron Letters 54 (2013) 3363–3365
3365
C
H
F
E
G
# eq.
2.5
Acknowledgments
2.3
2.1
1.9
1.7
1.5
1.3
1.1
0.9
0.7
0.5
0.3
0.1
0.0
This work was funded by these agencies: FQRNT (Québec),
NSERC (Canada) and CFI (crystallography facility).
Supplementary data
Supplementary data (1H and 13C NMR spectral assignments, ele-
mental analyses and X-ray crystallography data) associated with
this article can be found, in the online version, at http://
dx.doi.org/10.1016/j.tetlet.2013.04.074. These data include MOL
files and InChiKeys of the most important compounds described
in this article.
C
H
F
E
G
References and notes
7.9 7.8 7.7 7.6 7.5 7.4 7.3 7.2 7.1 7.0 6.9 6.8 6.7 ppm
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