Self-assembled coordination cage derived from small-sized pyridinophane

Article abstract of DOI:10.1016/j.tetlet.2006.07.007

The dithia[3.3]pyridinophane consisting of two pyridine rings has been found out to assume the syn-structure by the X-ray crystallography, meaning the two nitrogen atoms point in the same direction. From this cyclophane and cis-protected palladium(II), the self-assembled coordination molecular cage has been constructed.

Full text of DOI:10.1016/j.tetlet.2006.07.007

Tetrahedron Letters 47 (2006) 6607–6609
Self-assembled coordination cage derived
from small-sized pyridinophane
a
a
Akihiko Tsuge,a,b, Ayumi Matsubara, Tetsuji Moriguchi,
*
Yoshihisa Seic and Kentaro Yamaguchic
aDepartment of Applied Chemistry, Kyushu Institute of Technology, Tobata-ku, Kitakyushu 804-8550, Japan
bInstitute of Materials Chemistry and Engineering, Kyushu University, Higashi-ku, Fukuoka 812-8581, Japan
cFaculty of Pharmaceutical Science at Kagawa Campus, Tokushima Bunri University, Kagawa 769-2193, Japan
Received 26 May 2006; revised 4 July 2006; accepted 6 July 2006
Available online 28 July 2006
Abstract—The dithia[3.3]pyridinophane consisting of two pyridine rings has been found out to assume the syn-structure by the
X-ray crystallography, meaning the two nitrogen atoms point in the same direction. From this cyclophane and cis-protected
palladium(II), the self-assembled coordination molecular cage has been constructed.
Ó 2006 Elsevier Ltd. All rights reserved.
The self-assembly between specific metal centers and
selected pyridine-based ligands could give rise to well-
defined discrete supramolecular architectures such as
macrocycles, cages, tubes, and capsules.1 On the other
hand, cyclophanes known as bridged aromatic com-
pounds have been intensively studied from various
points of view for the last few decades.2 Among them
large-sized cyclophanes capable of forming an inner cav-
ity have been playing a central role as synthetic recep-
tors in molecular recognition.3 On account of this
background, large-sized cyclophanes represented by
calixarenes4 or resorcinarenes5 have been employed as
a component to create cavitand-based nanoscale cage
via metal coordination. On the contrary, small-sized
cyclophanes can be characterized by their aromatic com-
ponents fixed in a forced proximity and their particular
orientation. Considering their unique three-dimensional
structure and conformational mobility, the small-sized
cyclophanes possibly provide the fascinating supramo-
lecular self-assembly upon coordination. However, to
our best knowledge, there have been no reports on coor-
dination-driven self-assembly from small-sized cyclo-
phane components.
assume a syn conformation with two aromatic rings
located in face-to-face orientation. This simple structure
of the [3.3]metacyclophane system can be considered
suitable for formation of self-assembled coordination
cage. Taking the method developed by Fujita into
account, the cyclophane should have several pyridine
units. Thus, as a primary candidate we have focused
on dithia[3.3](3,5)pyridinophane 1. In this communica-
tion we will describe formation of a molecular cage
based on the small-sized pyridinophane 1.
Repeating the reported method6 to prepare the pyridi-
nophane 1 has resulted in poor yield. So we have mod-
ified this method to obtain the desired pyridinophane 1
in better yield. Direct chlorination of 3,5-lutidine with
NCS gave a mixture of monochloromethyl and bis-
(chloromethyl)compounds. A pure 3,5-bis(chloromethyl)
pyridine 2 could be successfully isolated by careful sep-
aration of the mixture employing a column chromato-
graphy. Subsequently 3,5-bis(mercaptomethyl)pyridine
3 was obtained by the conventional method from 2.
Cyclization of 2 and 3 using Cs2CO3 as a base under
highly dilute condition afforded the desired pyridino-
phane 17 in 45% yield (Scheme 1).
In our research on a series of cyclophanes we have
shown that most of dithia[3.3]metacyclophanes tend to
It should be critical to know the conformation of 1 in
order to form a desired cage-shaped assembly based
on the cyclophane compounds because they exhibit con-
formational variety. However, to our best knowledge
the X-ray crystal analysis of 1 has never been done yet.
*
Corresponding author. Tel.: +81 93 884 3317; fax: +81 93 884
3075; e-mail addresses: author@institute.edu; tsuge@che.kyutech.
ac.jp
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.07.007

6608
A. Tsuge et al. / Tetrahedron Letters 47 (2006) 6607–6609
Ha
N
ClH C
CH Cl HSCH
CH SH
2
2
2
2
+
S
S
Cs CO
Hb
N
N
2
3
3
2
Hc
N
1
Scheme 1. Synthesis of the cyclophane 1.
Figure 2. 1H NMR spectra of 1 and 5 in DMSO-d6 at 30 °C.
Figure 1. Single-crystal X-ray structure of 1.
So we have carried out the analysis of the conforma-
tional structure of 1.
dinophane 1 gives one singlet (d 3.90) for bridge protons
(Hb and Hc), in the spectrum of 5, bridge protons
appear as a set of doublets (d 3.97, J 12 and d 4.13, J
12). Such a spectral change is quite often observed with
a decrease in temperature for these kinds of dithia-
[3.3]metacyclophanes.8 This behavior can be explained
by dynamic conformational changes of cyclophanes,
meaning that a rapid ring inversion in the cyclophanes
at higher temperature is suppressed to a great extent
as the temperature is lowered. Thus, in this case flexibil-
ity of the pyridinophane 1 is considered to be depressed
by complexation of the pyridine nitrogen with Pd.
As shown in Figure 1, the syn conformation was con-
firmed for 1 from the X-ray analysis. A boat-chair
shape observed for the bridging is very interesting, so
details of conformational properties of 1 and related
compounds will be discussed elsewhere.
The pyridinophane 1 and cis-protected palladium(II)
complex (en)Pd(NO3)2 4 were combined in 1:1 stoichi-
ometry in water–methanol to afford the colorless pow-
der 5 which was then washed with methanol (Scheme 2).
1
This complexation is also supported by a downfield shift
(from d 7.94 to d 8.55) of the proton (Ha) adjacent to the
pyridine nitrogen. The formation of the cage structure
shown in Scheme 2 might be expected from these
NMR data.
The H NMR spectrum of the complex 5 in DMSO is
shown in Figure 2 together with 1. Upon complexation,
some impurities have been produced. Although the pyri-
H2
N
Pd
ONO2
4+
N
N
Pd
It has been known the cold-spray ionization mass spec-
trum (CSI-MS)9 is a powerful tool to obtain strong evi-
dence for the formation of supramolecular structure. In
order to dissolveꢀ5 in acetonitrile the counter anion was
replaced by PF6 to prepare the complex 6. Further
evidence for formation of cage structure was provided
by the CSI-MS (Fig. 3) of 6 ðPF6ꢀÞ, wherein the molec-
N
N
N
N
N
ONO2
N
H2
S
S
S
S
S
4
S
N
Pd
N
N
1
-
NO3
4
ular ion peaks of 6 were observed at m/z 1316.7
2þ
½6 ꢀ ðPF6ꢀÞꢁþ (calcd 1316.75), 585.9 ½6 ꢀ ðPF6ꢀÞ2ꢁ
5
3þ
(calcd 585.89), and 342.3 ½6 ꢀ ðPF6ꢀÞ3ꢁ (calcd 342.28).
Scheme 2. Formation of the cage structure 5 based on 1.
Although a small amount of the cage structure with
other coordination (1:4 = 4:4) was also detected in the
CSI mass spectrum, the major component is the cage
structure 5 shown in Scheme 2.
Crystal data for 1: C14H14N2S2, M = 274.40, monoclinic,
a = 12.412(1), b = 16.403(2), c = 6.3676(9) A, b = 92.49(1)°,
U = 1295.2(3) A , T = 293 K, space group P21/n (no. 14), Z = 4,
˚
3
˚
Dc = 1.407 g/cmꢀ3, l(CuKa) = 3.566 cmꢀ1, 3142 reflections mea-
sured, 220 parameters refined, R1 = 0.0590 (for 2940 reflections with
I > 3.0r(I), wR2 = 0.1680 (for all data). CCDC 278767. Crystallo-
graphic data in cif format (Ref. CCDC 278767) can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
The molecular cage based on coordination of the
cyclophane compound to the metal could provide novel
possibilities for the field of supramolecular architecture
since cyclophane components have various unique
characteristics such as conformational diversity, trans-

A. Tsuge et al. / Tetrahedron Letters 47 (2006) 6607–6609
6609
2000; p 1; (d) Olenyuk, B.; Whiteford, J. A.; Fechtenko¨tter,
A.; Stang, P. J. Nature 1999, 398, 796; (e) Leininger, S.;
Olenyuk, B.; Stang, P. J. Chem. Rev. 2000, 100, 853.
2. For example, see: (a) Vo¨gtle, F. Cyclophane Chemistry;
Wiley: Chichester, 1989; (b) Diederich, F. Cyclophanes; The
Royal Society of Chemistry: Cambridge, 1991.
3. For example, see: (a) Vo¨gtle, F. Supramolecular Chemistry;
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Shinkai, S.; Sakamoto, S.; Yamaguchi, K. J. Org. Chem.
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S.; Sakamoto, S.; Yamaguchi, K. J. Am. Chem. Soc. 2001,
123, 3872.
Figure 3. Cold-spray ionization mass spectrum of 6.
annular p electronic interaction, molecular recognition
and so on. Studies on cage formation from various cyc-
lophanes with exclusive molar ratio are currently under-
way in our laboratory.
5. Kobayashi, K.; Yamada, Y.; Yamasaka, M.; Sei, Y.;
Yamaguchi, K. J. Am. Chem. Soc. 2004, 126, 13896.
6. Kawashima, T.; Kurioka, S.; Tohda, Y.; Ariga, M.; Mori,
Y.; Misumi, S. Chem. Lett. 1985, 1289.
7. Colorless prisms. mp 235–238 °C (toluene); (Found: C,
61.03; H, 5.32; N, 10.04. Calcd for C14H14N2S2: C, 61.28;
H, 5.14; N, 10.21%); dH (400 MHz; CDCl3; Me4Si)
3.81 (8H, s), 7.54 (2H, s), 8.03 (4H, s); m/z (EI) 274
(M+).
References and notes
1. (a) Fujita, M.; Ogura, K. Bull. Chem. Soc. Jpn. 1996, 69,
1471; (b) Fujita, M. Chem. Soc. Rev. 1998, 27, 417; (c)
Biradha, K.; Fujita, M. In Advances in Supramolecular
Chemistry; Gokel, G. W., Ed.; JAI press: Connecticut,
8. Mitchell, R. H. J. Am. Chem. Soc. 2002, 124, 2352.
9. Yamaguchi, K. J. Mass Spectrom. 2003, 38, 473.