Construction and charge-transfer complexation of adamantane-based macrocycles and a cage with aromatic ring moieties

Article abstract of DOI:10.1021/jo9018842

(Figure Presented) Adamantane-based macrocycles and a cage with aromatic ring moieties have been developed and structurally revealed by X-ray crystallographic analysis. The dimerized (1) and trimerized (2) macrocycles of binary molecules based on adamanta

Full text of DOI:10.1021/jo9018842

pubs.acs.org/joc
Construction and Charge-Transfer Complexation of Adamantane-Based
Macrocycles and a Cage with Aromatic Ring Moieties
Masahide Tominaga,* Hyuma Masu, and Isao Azumaya*
Faculty of Pharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University, 1314-1 Shido, Sanuki,
Kagawa 769-2193, Japan
tominagam@kph.bunri-u.ac.jp; azumayai@kph.bunri-u.ac.jp
Received August 31, 2009
Adamantane-based macrocycles and a cage with aromatic ring moieties have been developed and
structurally revealed by X-ray crystallographic analysis. The dimerized (1) and trimerized (2)
macrocycles of binary molecules based on adamantane with acetylenic aromatic ring moieties were
designed and effectively synthesized. Similarly, a cryptand-like macrobicyclic cage (3) was con-
structed from a trisubstituted adamantane derivative. Single-crystal X-ray analysis revealed that
both cyclic compounds have nearly a rectangular shape with or without a solvent molecule in the
cavity. The macrobicyclic cage has an inner space and accommodates a chloroform molecule via
C-H π interactions. Macrocycles and cage encapsulate 1,3,5-trinitrobenzene (4) as an electron-
3 3 3
poor guest in a one-to-one complex via charge-transfer interactions in a parallel fashion, and showed
the formation of molecular networks such as columns, tubes, 2D layers, and 3D networks composed
of two different types through noncovalent interactions in the solid state.
Introduction
functional materials in the fields of organic and materials
chemistry.1 Inspired by the remarkable functionality of
macrocyclic structures, significant attention has been direc-
ted to the creation of macrocycles for their potential applica-
tions in areas such as molecular recognition, transmembrane
transport, ion-channel formation, and gas adsorption.1,2 A
number of synthetic routes have been developed to produce
various macrocyclic compounds from simple organic mole-
cules and cycles with diameters of up to several nanometers
such as calixarenes,3 calixpyrroles,4 and so on5 have been
In the last two decades, two- and three-dimensional host
molecules have been investigated as attractive platforms for
*To whom correspondence should be addressed. M.T.: phone 81-87-894-
5111 ex. 6305, fax 81-87-894-0181. I.A.: phone 81-87-894-5111 ex. 6308, fax
81-87-894-0181.
(1) (a) Moore, J. S. Acc. Chem. Res. 1997, 30, 402–413. (b) Bunz, U. H. F.;
Rubin, Y.; Tobe, Y. Chem. Soc. Rev. 1999, 28, 107–119. (c) Haley, M. M.;
Pak, J. J.; Brand, S. C. Top. Curr. Chem. 1999, 201, 81–130. (d) Zhao, D.;
Moore, J. S. Chem. Commun. 2003, 807–818. (e) Yamaguchi, Y.; Yoshida, Z.
€
Chem.;Eur. J. 2003, 9, 5430–5440. (f) Hoger, S. Angew. Chem., Int. Ed.
2005, 44, 3806–3808. (g) Oshovsky, G. V.; Reinhoudt, D. N.; Verboom, W.
Angew. Chem., Int. Ed. 2007, 46, 2366–2393.
(3) (a) Gutsche, C. D. Calixarenes; The Royal Society of Chemistry: Cam-
bridge, UK, 1989. (b) Gutsche, C. D. Calixarenes Revisited; The Royal Society of
Chemistry: Cambridge, UK, 1998. (c) Calixarenes in Action; Mandolini, L.,
Ungaro, R., Eds.; Imperial College Press: London, UK, 2000. (d) Lumetta, G. J.;
Rogers, R. D.; Gopalan, A. S. Calixarenes for Separation; American Chemical
Society: Washington, DC, 2000.
(4) (a) Gale, P. A.; Sessler, J. L.; Kral, V. Chem. Commun. 1998, 1–8. (b)
ꢀ
´
Anzenbacher, P. Jr.; Jursıkova, K.; Lynch, V. M.; Gale, P. A.; Sessler, J. L.
J. Am. Chem. Soc. 1999, 121, 11020–11021. (c) Anzenbacher, P. Jr.;
(2) (a) Motesharei, K.; Ghadiri, M. R. J. Am. Chem. Soc. 1997, 119,
11306–11312. (b) Rathore, R.; Lindeman, S. V.; Rao, K. S. S. P.; Sun, D.;
Kochi, J. K. Angew. Chem., Int. Ed. 2000, 39, 2123–2127. (c) Mahender, J. Y.;
Dewal, B.; Shimizu, L. S. J. Am. Chem. Soc. 2006, 128, 8122–8123. (d)
Cheney, M. L.; McManus, G. J.; Perman, J. A.; Wang, Z.; Zaworotko, M. J.
Cryst. Growth Des. 2007, 7, 616–617. (e) Dalgarno, S. J.; Thallapally, P. K.;
Barbour, L. J.; Atwood, J. L. Chem. Soc. Rev. 2007, 36, 236–245. (f)
Thallapally, P. K.; McGrail, B. P.; Dalgarno, S. J.; Schaef, H. T.; Tian, J.;
Atwood, J. L. Nat. Mat. 2008, 7, 146–150.
ꢀ
ꢀ
´
Jursıkova, K.; Sessler, J. L. J. Am. Chem. Soc. 2000, 122, 9350–9351.
8754 J. Org. Chem. 2009, 74, 8754–8760
Published on Web 10/21/2009
DOI: 10.1021/jo9018842
r
2009 American Chemical Society

Tominaga et al.
JOCArticle
obtained. The construction of host-guest complexes formed
between macrocycles and guest molecules can offer a good
foundation for understanding guest-induced structural mo-
tifs and molecular recognition, leading to the development of
unique chemical and physical properties.6 The macrocyclic
host molecules allow complexation with a wide variety of
ions, atoms, and small molecules through noncovalent inter-
actions such as hydrogen bonding, hydrophobic inter-
actions, aromatic stacking, and van der Waals interactions.7
In particular, macrocycles consisting of electron-rich aroma-
tic rings are able to form complexes with electron-deficient
guest molecules via charge-transfer interactions.8 Such
macrocycles have been used in the design of host-guest
inclusion compounds9 and diverse supramolecular architec-
tures such as catenanes,10 rotaxanes,11 folded aedamers,12
and macrocycle-tweezer complexes.13 However, the compo-
nents of such systems have generally involved substruc-
tures10-14 such as N-benzylbipyridinium units, pyromellitic
diimide parts, and alkoxynaphthalene moieties, and macro-
cycles consisting of alternative units are essential in the
design of solid state structures and functions based on
host-guest chemistries. Adamantane and its derivatives15
are a class of structurally unique compounds because they
are mechanically rigid and conformationally well-defined.
Adamantane derivatives as rigid, tetrahedrally symmetrical
compounds with two- or three-dimensional scaffolds have
been found in numerous applications in medicinal chemistry
and material sciences. However, the design and synthesis of
adamantane-based hosts and their applications in host-
guest chemistry remain largely unexplored. Recently, we
have demonstrated that the complexation of disubstitu-
ted adamantane consisting of 2,6-dimethoxyphenol as an
electron-rich unit with 1,3,5-trinitrobenzene16 as an electron-
poor guest assembles in the solid state to form a molecular
network through donor-acceptor interactions.17 We have
therefore applied this moiety as a structural fragment to
construct macrocyclic and cage frameworks, in which two or
three units of binary molecules based on adamantane, and
two units of trisubstituted adamantane are covalently linked
by a 1,6-dioxahexa-2,4-diyne spacer with relatively rigid and
directional characteristics. Acetylenic units are used as
bridges to provide rigidity to the cyclic framework and the
number of acetylenic units in the bridge and its connectivity
to the arene units define the size and shape of the cavity in the
macrocycle and cage.18 In this paper, we report the construc-
tion and structural analysis of two types of macrocycles and a
cryptand-like macrobicyclic cage, which encapsulate elec-
tron-poor guest molecule in a one-to-one complex via
charge-transfer interactions. Further, macrocycles and cage
including guest molecule showed the generation of unique
molecular networks in the crystal lattice.
€
(5) (a) Gerkensmeier, T.; Iwanek, W.; Agena, C.; Frohlich, R.; Kotila, S.;
€
Nather, C.; Mattay, J. Eur. J. Org. Chem. 1999, 2257–2262. (b) Atwood, J. L.;
Barbour, L. J.; Jerga, A. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 4837–4841.
(c) Gokel, G. W.; Barbour, L. J.; Ferdani, R.; Hu, J. Acc. Chem. Res. 2002,
35, 878–886. (d) Azumaya, I.; Okamoto, T.; Imabeppu, F.; Takayanagi, H.
Tetrahedron 2003, 59, 2325–2331. (e) Gokel, G. W.; Leevy, W. M.; Weber, M.
E. Chem. Rev. 2004, 104, 2723–2750. (f) Ishibashi, K.; Tsue, H.; Tokita, S.;
Matsui, K.; Takahashi, H.; Tamura, R. Org. Lett. 2006, 8, 5991–5994. (g)
Barrett, E. S.; Dale, T. J.; Rebek, J. Jr. J. Am. Chem. Soc. 2008, 130, 2344–
2350. (h) Tsue, H.; Matsui, K.; Ishibashi, K.; Takahashi, H.; Tokita, S.; Ono,
K.; Tamura, R. J. Org. Chem. 2008, 73, 7748–7755.
(6) (a) Dalgarno, S. J.; Tucker, S. A.; Bassil, D. B.; Atwood, J. L. Science
2005, 309, 2037–2039. (b) Dalgarno, S. J.; Cave, G. W. V.; Atwood, J. L.
Angew. Chem., Int. Ed. 2006, 45, 570–574. (c) Ananchenko, G. S.; Udachin,
K. A.; Dubes, A.; Ripmeester, J. A.; Perrier, T.; Coleman, A. W. Angew.
Chem., Int. Ed. 2006, 45, 1585–1588. (d) Hisaki, I.; Sakamoto, Y.;
Shigemitsu, H.; Tohnai, N.; Miyata, M. Cryst. Growth Des. 2009, 9, 414–
420. (e) Katagiri, K.; Kato, T.; Masu, H.; Tominaga, M.; Azumaya, I. Cryst.
Growth Des. 2009, 9, 1519–1524.
(7) (a) Chang, K.-J.; Moon, D.; Lah, M. S.; Jeong, K.-S. Angew. Chem.,
Int. Ed. 2005, 44, 7926–7929. (b) Lintuluoto, J. M.; Nakayama, K.; Setsune,
J. Chem. Commun. 2006, 3492–3494. (c) Kang, S.-W.; Gothard, C. M.;
Maitra, S.; Wahab, A.-T.; Nowick, J. S. J. Am. Chem. Soc. 2007, 129, 1486–
1487. (d) Emond, S. J.; Debroy, P.; Rathore, R. Org. Lett. 2008, 10, 389–392.
(e) Li, Y.; Flood, A. H. Angew. Chem., Int. Ed. 2008, 47, 2649–2652. (f)
€
Hoffmann, M.; Karnbratt, J.; Chang, M.-H.; Herz, L. M.; Albinsson, B.;
Anderson, H. L. Angew. Chem., Int. Ed. 2008, 47, 4993–4996. (g) Makha, M.;
Scott, J. L.; Strauss, C. R.; Sobolev, A. N.; Raston, C. L. Cryst. Growth Des.
2009, 9, 483–487.
(8) (a) Rastogi, R. P.; Bassi, P. S.; Chadha, L. S. J. Phys. Chem. 1963, 67,
2569–2573. (b) Rastogi, R. P.; Singh, N. B. J. Phys. Chem. 1966, 70, 3315–
3324. (c) Rastogi, R. P.; Singh, N. B. J. Phys. Chem. 1968, 72, 4446–4449. (d)
Paul, I. C.; Curtin, D. Y. Acc. Chem. Res. 1973, 6, 217–225. (e) Curtin, D. Y.;
Paul, I. C. Chem. Rev. 1981, 81, 525–541. (f) Imai, Y.; Tajima, N.; Sato, T.;
Kuroda, R. Org. Lett. 2006, 8, 2941–2944. (g) Imai, Y.; Kido, S.; Kamon, K.;
Kinuta, T.; Sato, T.; Tajima, N.; Kuroda, R.; Matsubara, Y. Org. Lett. 2007,
9, 5047–5050. (h) Imai, Y.; Kinuta, T.; Kamon, K.; Tajima, N.; Sato, T.;
Kuroda, R.; Matsubara, Y. Cryst. Growth Des. 2009, 9, 2393–2397.
(9) (a) Srinivasan, M.; Sankararaman, S.; Hopf, H.; Dix, I.; Jones, P. G.
J. Org. Chem. 2001, 66, 4299–4303. (b) Nielsen, K. A.; Jeppesen, J. O.;
Levillain, E.; Thorup, N.; Becher, J. Org. Lett. 2002, 4, 4189–4192. (c)
Nielsen, K. A.; Cho, W.-S.; Jeppesen, J. O.; Lynch, V. M.; Becher, J.; Sessler,
J. L. J. Am. Chem. Soc. 2004, 126, 16296–16297. (d) Koshkakaryan, G.;
Klivansky, L. M.; Cao, D.; Snauko, M.; Teat, S. J.; Struppe, J. O.; Liu, Y.
J. Am. Chem. Soc. 2009, 131, 2078–2079.
(10) (a) Hamilton, D. G.; Sanders, J. K. M.; Davies, J. E.; Clegg, W.; Teat,
S. J. Chem. Commun. 1997, 897–898. (b) Hamilton, D. G.; Feeder, N.; Prodi,
L.; Teat, S. J.; Clegg, W.; Sanders, J. K. M. J. Am. Chem. Soc. 1998, 130,
1096–1097. (c) Hamilton, D. G.; Feeder, N.; Teat, S. J.; Sanders, J. K. M.
New J. Chem. 1998, 22, 1019–1021. (d) Hansen, J. G.; Feeder, N.; Hamilton,
D. G.; Gunter, M. J.; Becher, J.; Sanders, J. K. M. Org. Lett. 2000, 2, 449–
452.
(13) (a) Colquhoun, H. M.; Zhu, Z.; Williams, D. J. Org. Lett. 2003, 5,
4353–4356. (b) Colquhoun, H. M.; Zhu, Z.; Cardin, C. J.; Gan, Y. Chem.
Commun. 2004, 2650–2652. (c) Colquhoun, H. M.; Zhu, Z.; Cardin, C. J.;
Gan, Y.; Drew, M. G. B. J. Am. Chem. Soc. 2007, 129, 16163–16174.
(14) (a) Colquhoun, H. M.; Williams, D. J.; Zhu, Z. J. Am. Chem. Soc.
2002, 124, 13346–13347. (b) Zhou, Q.-Z.; Jiang, X.-K.; Shao, X.-B.; Chen,
G.-J.; Jia, M.-X.; Li, Z.-T. Org. Lett. 2003, 5, 1955–1958. (c) Vignon, S. A.;
Jarrosson, T.; Iijima, T.; Tseng, H.-R.; Sanders, J. K. M.; Stoddart, J. F. J.
J. Am. Chem. Soc. 2004, 126, 9884–9885. (d) Iwanaga, T.; Nakamoto, R.;
Yasutake, M.; Takemura, H.; Sako, K.; Shinmyozu, T. Angew. Chem., Int.
Ed. 2006, 45, 3643–3647. (e) Koshkakaryan, G.; Klivansky, L. M.; Cao, D.;
Snauko, M.; Teat, S. J.; Struppe, J. O.; Liu, Y. J. Am. Chem. Soc. 2009, 131,
2078–2079.
(15) (a) Maison, W.; Frangioni, J. V.; Pannier, N. Org. Lett. 2004, 6, 4567–
4569. (b) Kitagawa,T.;Idomoto, Y.;Matsubara,H.;Hobara, D.;Kakiuchi, T.;
Okazaki, T.; Komatsu, K. J. Org. Chem. 2006, 71, 1362–1369. (c) Nasr, K.;
Pannier, N.; Frangioni, J. V.; Maison, W. J. Org. Chem. 2008, 73, 1056–1060.
(d) Pannier, N.; Maison, W. Eur. J. Org. Chem. 2008, 1278–1284.
(16) (a) Biradha, K.; Nangia, A.; Desiraju, G. R.; Carrell, C. J.; Carrell,
H. L. J. Mater. Chem. 1997, 7, 1111–1122. (b) Thallapally, P. K.; Katz, A. K.;
Carrell, H. L.; Desiraju, G. R. CrystEngComm 2003, 5, 87–92. (c) Jetti, R. K.
R.; Boese, R.; Thallapally, P. K.; Desiraju, G. R. Cryst. Growth Des. 2003, 3,
1033–1040. (d) Thallapally, P. K.; Jetti, R. K. R.; Katz, A. K.; Carrell, H. L.;
Singh, K.; Lahiri, K.; Kotha, S.; Boese, R.; Desiraju, G. R. Angew. Chem.,
Int. Ed. 2004, 43, 1149–1155.
(11) (a) Anelli, P. L.; Spencer, N.; Stoddart, J. F. J. Am. Chem. Soc. 1991,
113, 5131–5133. (b) Bissell, R. A.; Cordova, E.; Kaifer, A. E.; Stoddart, J. F.
Nature 1994, 369, 133–137. (c) Amabilino, D. B.; Stoddart, J. F. Chem. Rev.
(17) Tominaga, M.; Katagiri, K.; Azymaya, I. Cryst. Growth Des. 2009, 9,
3692–3696.
ꢀ
1995, 95, 2725–2828. (d) Dichtel, W. R.; Miljanic, O. S.; Zhang, W.; Spruell,
J. M.; Patel, K.; Aprahamian, I.; Heath, J. R.; Stoddart, J. F. Acc. Chem. Res.
2008, 41, 1750–1761.
(18) (a) Tobe, Y.; Nagano, A.; Kawabata, K.; Sonora, M.; Naemura, K.
Org. Lett. 2000, 2, 3265–3268. (b) Baxter, P. N. W. J. Org. Chem. 2001, 66,
€
(12) (a) Lokey, R. S.; Iverson, B. L. Nature 1995, 375, 303–305. (b)
Cubberley, M. S.; Iverson, B. L. J. Am. Chem. Soc. 2001, 123, 7560–7563. (c)
Gabriel, G. J.; Iverson, B. L. J. Am. Chem. Soc. 2002, 124, 15174–15175. (d)
Gabriel, G. J.; Sorey, S.; Iverson, B. L. J. Am. Chem. Soc. 2005, 127, 2637–
2640.
4170–4179. (c) Fuhrmann, G.; Debaerdemaeker, T.; Bauerle, P. Chem.
Commun. 2003, 948–949. (d) Werz, D. B.; Gleiter, R.; Rominger, F.
J. Org. Chem. 2004, 69, 2945–2952. (e) Kivala, M.; Mitzel, F.; Boudon, C.;
Gisselbrecht, J.-P.; Seiler, P.; Gross, M.; Diederich, F. Chem. Asian J. 2006,
1, 479–489.
J. Org. Chem. Vol. 74, No. 22, 2009 8755

Tominaga et al.
JOCArticle
SCHEME 1. The Synthesis of Macrocycles 1 and 2
SCHEME 2. The Synthesis of a Cryptand-like Macrobicyclic
Cage 3
respectively (Figure 1b). The cyclic framework has a Cs
symmetry in the solid state and is ascribed to the packing
effect. Specifically, macrocycle 2 is relatively flexible in
comparison to 1 such that the cavity was filled with a portion
of the macrocycle. Single crystals of compound 3 were
obtained from vapor diffusion of cyclohexane into a chloro-
form solution of 3. X-ray crystallographic analysis showed
that the crystal belonged to the space group P21/c, which
contains one molecule of both 3 and cyclohexane, and two
molecules of chloroform in the unit cell (Figure 1c,d). The
crystal structure reveals that the distance between the two
bridgehead carbons in the two adamantane moieties of 3 is
12.90 A, and the two sets of distances between the methylene
carbons in the linker units are 13.54, 12.98, and 12.50 A and
13.46, 13.17, and 12.25 A, respectively. The cage 3 in the solid
state is twisted by the rotation of the triphenyladamantane
moieties to minimize the more energetically favorable struc-
ture and is due to the flexibility of the 1,6-dioxahexa-2,
4-diyne bridges relative to each other. Therefore, the cage
framework contains a set of enantiomeric helical conformers
with left- and right-handed helical twists in the crystal lattice.
The angle of the twist between the two adamantane parts at
both ends of the molecule is 52.6°. One chloroform molecule
was included in the cavity of cage 3, where intermolecular
Results and Discussion
The copper-mediated oxidative acetylene dimerization has
been utilized as ring closure reactions to prepare the macro-
cycle and cage compounds with well-defined structures
because of the directional property of the diacetylenic bridge
unit. To construct a macrocyclic framework with a large
cavity, macrocycles were designed and effectively synthe-
sized in three steps from commercially available starting
materials (Scheme 1). The reaction of 2,6-dimethoxyphenol
with 1,3-adamantanediol gave a binary molecule based on
adamantane (85%), which was subsequently treated with
propargyl bromide to afford disubstituted adamantane with
a yield of 93%. The Hay acetylene coupling provided
dimerized macrocycle 1 (71%) and trimerized macrocycle 2
(18%) in high-dilution conditions. The molecular cage 3 was
also readily synthesized from 1,3,5-adamantanetriol in three
steps according to Scheme 2. The macrocycles 1, 2, and 3
were characterized by 1H and 13C NMR spectroscopy,
elemental analysis, and FAB mass spectroscopy. The results
of the characterization are in full agreement with the struc-
tures presented. The macrocyclic structures of 1-3 are
identified from the 1H and 13C NMR spectra, which showed
only one signal for the methine proton and carbon of the
adamantane moieties, respectively. The singlet for the
aromatic protons indicates that each aromatic ring rotates
freely at room temperature in the macrocyclic framework.
Single crystals of macrocycles 1 and 2 were obtained from
vapor diffusion of hexane into a chloroform solution of 1.
The crystal 1 crystallized in the triclinic system, space group
P1, and included one molecule of 1 and two molecules of
chloroform in the unit cell. X-ray crystallographic analysis
showed that the macrocyclic structure of 1 was a rectangular
shape, where the distance between the centroids of opposing
rings is 15.85 and 8.04 A, respectively (Figure 1a). Two
chloroform molecules were accommodated in the cavity of
C-H π interactions (the distance measured from the
3 3 3
center of the ring to the carbon atom of the chloroform
molecule is 3.89 A) were observed between the methine
proton of the chloroform molecule and the aromatic ring
part.
The adamantane-based macrocycles and cage containing
aromatic ring moieties as electron donors have a rigid frame-
work and are expected to potentially entrap the electron-
deficient guests. 1,3,5-Trinitrobenzene (4) was chosen as a
substrate, which represents an agent for crystalline π-π
donor-acceptor complexes. In fact, the adamantane-based
macrocycles and cage encapsulate electron-poor guest mo-
lecule in a one-to-one complex via charge-transfer interac-
macrocycle 1, where intermolecular C-H O interactions
3 3 3
(the C O distance is 3.20 A) were observed between the
tions in the solid state. Single crystals of complex 1 4 were
3
3 3 3
methine proton of the chloroform molecule and the oxygen
atom of the methoxy groups. The crystal 2 crystallized in the
orthorhombic system, space group Pnma, and included only
molecule of 2. In the crystals of 2, macrocyclic structure of 2
is a rectangular shape, where the distances between the
centroids of opposing rings are 12.29, 22.42, and 12.29 A,
obtained as pale yellow blocks by vapor diffusion of hexane
into a chloroform solution containing 1 and 4 as an electron
donor in 1:4 molar ratio. The crystal of complex 1 4 was
3
significantly different in color from that of the component
solids. The crystal of complex 1 4 crystallized in the mono-
clinic system, space group P21/c, and included one molecule
3
8756 J. Org. Chem. Vol. 74, No. 22, 2009

Tominaga et al.
JOCArticle
FIGURE 1. Crystal structures of 1 (a), 2 (b), side view of 3 (c), and top view of 3 (d) in the thermal ellipsoid model.
FIGURE 2. (a) Crystal structure of complex 1 4 in the thermal ellipsoid model. Guest molecules located outside of the cavity are omitted for
clarity. Side view (b) and top view (c) of the tubular structure in the packing diagram of complex 1 4. The guest molecules 4 are colored
magenta. Hydrogen bonds are indicated by black dashes.
3
3
J. Org. Chem. Vol. 74, No. 22, 2009 8757

Tominaga et al.
JOCArticle
FIGURE 3. (a) Crystal structure of the complex 2 4 in the thermal ellipsoid model. The chloroform molecules outside of the cavity have been
omitted for clarity. Side view (b) and top view (c) of the columnar structure in the packing diagram of complex 2 4. Overall view of the packing
3
3
structure including the chloroform molecules (d). The guest molecules 4 are colored magenta. The molecules of neighboring columns are
colored cyan.
of 1 and three molecules of 4 in the asymmetric unit. The
crystal structure showed that the macrocyclic framework is
also a rectangular shape, where the measured distance
between the centroids of opposing rings are 15.72 and
7.59 A, respectively (Figure 2a). However, the shape is
slightly distorted in comparison to crystal 1 because two
aromatic ring moieties of 1 are stacked on the π-face of 4 with
donor-acceptor interactions in a parallel fashion. These
distances are slightly longer than the van der Waals dia-
meters of two aromatic rings, but the maximum contacts of
the aromatic rings required for a CT-type electronic inter-
action are realized. The distance between the phenyl ring of 1
and 4 is 3.57 and 4.15 A (measured from the center of the ring
to the center of the ring), and the dihedral angle of a cofacial
pair is slightly tilted at 8.3° and 8.6°. This complex stacks
regularly to form a tubular structure via intermolecular
methoxy groups of the aromatic ring moieties (the C
O
3 3 3
distance ranged from 3.43 to 4.06 A). Interestingly, two
molecules of 4 were located at the exterior of the macrocycle
and formed a charge-transfer complex with residual aro-
matic ring moieties of 1. Consequently, the 3D network
formed was composed of two different types of layers, in
which the host layer (including the guest) and the guest layer
were stacked in an alternating fashion.
Single crystals of complex 2 4 were also obtained as pale
3
yellow blocks by vapor diffusion of hexane into a chloroform
solution containing 2 and 4 in 1:6 molar ratio. The crystal of
complex 2 4 crystallized in the triclinic system, space group
P1, and included one molecule each of 2, 4, and chloroform
in the asymmetric unit. In the crystals of complex 2 4, the
3
3
shape of 2 is significantly distorted, where the distances
between the centroids of opposing rings were 11.96, 22.57,
and 8.99 A, respectively (Figure 3a). The guest 4 was gripped
by macrocycle 2 in such a way that the electron-poor 4
formed a triple donor-acceptor π-stack with the electron-
rich aromatic ring systems of the macrocycle. The distance
between the aromatic ring of 2 and 4 is 3.70 and 3.59 A
(measured from the center of the ring to the center of the
ring), and the dihedral angle of a cofacial pair is tilted at 8.4°
and 12.7°. The host-guest complex packs into a columnar
structure in the crystal along the a axis (Figure 3b-d).
multiple C-H O interactions (the C O distance ranged
3 3 3 3 3 3
from 3.16 to 3.53 A) between the methoxy protons and the
oxygen atoms of the nitro groups in neighboring enclath-
rated 4 (Figure 2b,c). These results displayed that the pack-
ing of the host framework in the host-guest complex can be
controlled by the guest molecule. Guest 4 entrapped in the
1D array existed in two different orientations, which were
alternately aligned within the tubular structure. The tubular
structures were observed to assemble into a 2D layered
aggregation through C-H O interactions between the
Multiple C-H O interactions (the C O distance ranged
3 3 3
3 3 3 3 3 3
8758 J. Org. Chem. Vol. 74, No. 22, 2009

Tominaga et al.
JOCArticle
framework of 3 was slightly increased in comparison to the
structure of 3 alone (Figure 4a,b). This is because two
aromatic ring moieties of 3 are stacked on the π-face of 4
with donor-acceptor interactions occurring in a parallel
fashion. The distance between the phenyl ring of 3 and 4 is
3.55 A (measured from the center of the ring to the center of
the ring), and the dihedral angle of a cofacial pair is tilted at
14.2°. Cage molecules stack regularly to form a columnar
structure by intermolecular C-H π interactions between
3 3 3
the phenyl ring and the methylene protons of the linker unit
(the distance measured from the center of the ring to the
carbon atom of the methylene group is 3.57 A) that is aligned
with the a axis (Figure 4c). Interestingly, a microporous
structure was observed along the a axis in the one-dimen-
sional array.20
Conclusions
In conclusion, we have achieved macrocyclization of
di- and trisubstituted adamantane bearing acetylenic aroma-
tic ring parts by copper-mediated oxidative coupling and
isolated two types of macrocycles and cryptand-like macro-
bicyclic cage with a cavity, respectively. Crystallographic
analyses of the macrocycles and cage and their charge-
transfer complexes were realized. X-ray diffraction experi-
ments of the host-guest complexes revealed that the macro-
cycles and cage receptor was found to encapsulate the
electron-poor guest molecule via charge-transfer interac-
tions. Furthermore, guest molecules had an influence on
the packing of the host molecules, resulting in the generation
of crystalline solids such as columns, tubes, 2D layers, and
3D networks composed of two different types. We believe
that macrocycles and cage represent a versatile scaffold for a
new family of supramolecular architectures. The synthesis of
the corresponding larger host frameworks and their inclu-
sion phenomenon with other electron-deficient guest mole-
cules are the subject of the current studies.
Experimental Section
1,3-Bis(4-propargyloxy-3,5-dimethoxyphenyl)adamantine. A
mixture of 1,3-bis(4-hydroxy-3,5-dimethoxyphenyl)adaman-
tane (2.20 g, 5.00 mmol), propargyl bromide (0.98 mL, 13.0
mmol), and potassium carbonate (1.79 g, 13.0 mmol) in dry
DMF (50 mL) was stirred for 12 h at room temperature under an
argon atmosphere. The reaction mixture was poured into water
and then extracted with chloroform. The extract was washed
with water and brine and dried over Na2SO4. Evaporation of
solvent followed by silica gel column chromatography (eluent:
CHCl3) afford the title compound as a white solid (2.40 g, 4.65
FIGURE 4. Side view (a) and top view (b) of the crystal structure of
the complex 3 4 in the thermal ellipsoid model. Hydrogen atoms
3
and chloroform molecules are omitted for clarity. (c) Packing
diagram of the complex 3 4. The guest molecules are colored cyan.
The chloroform molecules are omitted for clarity.
3
mmol) in 93% yield. Mp 137-138 °C. FT-IR (ATR, cm-1
)
from 3.26 to 3.66 A) between the methylene protons of the
adamantane parts and the oxygen atoms and protons of the
methoxy groups were observed.
1
3279, 2907, 1586, 1507, 1448, 1122, 823. H NMR (400 MHz,
CDCl3, 27 °C) δ 6.60 (s, 4H), 4.68 (d, J = 2.4 Hz, 4H), 3.87 (s,
12H), 2.45 (t, J = 2.4 Hz, 2H), 2.33 (s, 2H), 2.00-1.78 (m, 12H).
13C NMR (125 MHz, CDCl3, 27 °C) δ 152.9, 147.0, 135.8, 102.3,
79.5, 74.6, 59.8, 56.1, 49.4, 42.1, 37.5, 35.7, 29.4. MS (FAB, m/z)
calcd for C32H37O6 (M þ Hþ) 517.25, found 517.7. Elemental
Single crystals of complex 3 4 were also obtained as pale
3
yellow blocks by vapor diffusion of hexane into a chloroform
solution containing 2 and 4 in 1:4 molar ratio.19 The crystal
of complex 3 4 crystallized in the monoclinic system,
3
Anal. Calcd for C32H36O6 0.05CHCl3: C, 73.66; H, 6.95.
3
space group C2/c, and included one molecule each of 3, 4,
and chloroform in the unit cell. The top view of the
crystal structure showed that the distortion of the capsule
Found: C, 73.82; H, 6.99.
Macrocycles 1 and 2. A solution of the 1,3-bis(4-propargyl-
oxy-3,5-dimethoxyphenyl)adamantane (0.21 g, 0.40 mmol),
copper(I) chloride (1.98 g, 20.0 mmol), and N,N,N0,N0-tetra-
(19) The determination of the formation constant of the CT complexes
between 3 and 4 with use of the Benesi-Hildebrand method and a nonlinear
curve-fitting procedure was attempted. The magnitude of the association
(20) Although solvent molecules (chloroform or water) may be included
in the void space, they could not be easily identified due to disorder.
constants was ca. 10 M-1
.
J. Org. Chem. Vol. 74, No. 22, 2009 8759

Tominaga et al.
JOCArticle
methylethylenediamine (TMEDA) (3.00 mL, 20.0 mmol) in dry
CH2Cl2 (800 mL) was stirred for 12 h at room temperature. The
reaction mixture was washed with water and brine and dried
over anhydrous Na2SO4. Evaporation of the solvent followed
by silica gel column chromatography (eluent: CHCl3) and gel
permeation chromatography (JAIGEL 1Hþ2H, CHCl3) afford
1 (145 mg, 0.14 mmol, 71%) and 2 (36.1 mg, 23.3 μmol, 18%) as
a white powder, respectively. 1: mp >300 °C dec. FT-IR (ATR,
cm-1) 2159, 1559, 1507, 1457, 1112, 795. 1H NMR (400 MHz,
CDCl3, 27 °C) δ 6.58 (s, 8H), 4.74 s, 8H), 3.83 (s, 24H), 2.34 (s,
4H), 2.07-1.77 (m, 24H). 13C NMR (125 MHz, CDCl3, 27 °C) δ
153.0, 147.2, 133.1, 102.3, 75.1, 70.8, 60.1, 56.2, 50.5, 42.0, 37.6,
35.8, 29.5. MS (FAB, m/z) calcd for C64H69O12 (M þ Hþ)
1,3,5-Tri(4-propargyloxy-3,5-dimethoxyphenyl)adamantane.
A mixture of 1,3,5-tri(4-hydroxy-3,5-dimethoxyphenyl)ada-
mantane (1.48 g, 2.50 mmol), propargyl bromide (0.74 mL,
9.75 mmol), and potassium carbonate (1.35 g, 9.75 mmol) in dry
DMF (50 mL) was stirred for 12 h at room temperature under an
argon atmosphere. The reaction mixture was poured into water
and then extracted with CHCl3. The extract was washed with
H2O and brine, then dried over Na2SO4. Evaporation of solvent
followed by silica gel column chromatography (eluent: CHCl3)
afford the title compound as a white solid (1.57 g, 2.23 mmol) in
89% yield. Mp 184-185 °C. FT-IR (ATR, cm-1) 3258, 2925,
1
2117, 1662, 1587, 1508, 1184, 1121, 999. H NMR (400 MHz,
CDCl3, 27 °C) δ 6.64 (s, 6H), 4.70 (d, J = 2.8 Hz, 6H), 3.88 (s,
18H), 2.56 (s, 3H), 2.45 (t, J = 2.4, 4.8 Hz, 3H), 2.10-1.99 (m,
12H). 13C NMR (125 MHz, CDCl3, 27 °C) δ 153.2, 146.4, 134.2,
102.6, 79.6, 74.7, 60.0, 56.4, 48.34, 41.5, 38.7, 30.1. MS (FAB, m/
z) calcd for C43H47O9 (M þ Hþ) 707.31, found 707.7. Elemental
1029.47, found 1029.3. Elemental Anal. Calcd for C64H68O12
3
0.2CHCl3: C, 73.22; H, 6.53. Found: C, 73.50; H, 6.87. 2:
mp >300 °C dec. FT-IR (ATR, cm-1) 2160, 1583, 1506, 1452,
1124, 794. 1H NMR (400 MHz, CDCl3, 27 °C) δ 6.51 (s, 12H),
4.66 (s, 12H), 3.76 (s, 36H), 2.26 (s, 6H), 1.92-1.71 (m, 36H). 13
C
Anal. Calcd for C43H46O9 0.2CHCl3: C, 71.01; H, 6.37. Found:
3
NMR (125 MHz, CDCl3, 27 °C) δ 153.0, 147.3, 133.4, 102.3,
75.3, 70.8, 60.4, 56.2, 49.4, 42.3, 37.6, 35.8, 29.5. MS (FAB, m/z)
calcd for C96H103O18 (M þ Hþ) 1543.71, found 1543.4. Ele-
C, 71.28; H, 6.48.
Cage 3. A solution of the 1,3,5-tri(4-propargyloxy-3,5-di-
methoxyphenyl)adamantane (0.56 g, 0.80 mmol), copper(I)
chloride (2.78 g, 24.0 mmol), and N,N,N0,N0-tetramethylethlene
diamine (3.60 mL, 24.0 mmol) in dry CH2Cl2 (320 mL) was
stirred for 12 h at room temperature under air. The reaction
mixture was washed with water and brine, then dried over
anhydrous Na2SO4. Evaporation of the solvent followed by
silica gel column chromatography (eluent: CHCl3) and gel
permeation chromatography (JAIGEL 1Hþ2H, CHCl3) afford
3 (56 mg, 40.0 μmol, 10%) as a white powder. Mp >300 °C dec.
FT-IR (ATR, cm-1) 2927, 2849, 2161, 1585, 1507, 1457, 1409,
mental Anal. Calcd for C96H102O18 0.33CHCl3: C, 73.06; H,
3
6.51. Found: C, 72.82; H, 6.85.
1,3,5-Tris(4-hydroxy-3,5-dimethoxyphenyl)adamantane.
A
mixture of 1,3,5-adamantanetriol (3.31 g, 18.0 mmol) and 2,6-
dimethoxyphenol (21.14 g, 81.0 mmol) in trifluoroacetic acid
(100 mL) and 1,2-dichloroethane (100 mL) in the presence of a
catalytic amount of trifluoromethanesulfonic acid was stirred at
90 °C for 12 h under an argon atmosphere. The solvents were
removed under reduced pressure, then the reaction mixture was
washed with H2O, saturated aqueous NaHCO3, H2O, and brine
and dried over Na2SO4. Evaporation of solvent followed by
silica gel column chromatography (eluent: CHCl3) afford the
title compound as a white solid (8.00 g, 13.5 mmol) in 75% yield.
Mp 220-221 °C. FT-IR (ATR, cm-1) 3498, 2929, 1604, 1517,
1408, 1211, 1107, 794, 747. 1H NMR (400 MHz, CDCl3, 27 °C) δ
6.65 (s, 6H), 5.43 (s, 3H), 3.91 (s, 18H), 2.55 (s, 1H), 2.08-1.98
(m, 12H). 13C NMR (125 MHz, CDCl3, 27 °C) δ 146.8, 141.4,
133.2, 102.2, 56.5, 48.7, 41.7, 38.4, 30.2. MS (FAB, m/z) calcd for
C34H41O9 (M þ Hþ) 593.27, found 593.6. Elemental Anal.
Calcd for C34H40O9: C, 68.90; H, 6.80. Found: C, 68.63; H,
6.83.
1
1123, 982, 752. H NMR (400 MHz, CDCl3, 27 °C) δ 6.64 (s,
12H), 4.79 (s, 12H), 3.77 (s, 36H), 2.57 (s, 2H), 2.17-1.98 (m,
24H). 13C NMR (125 MHz, CDCl3, 27 °C) δ 153.4, 146.5, 133.6,
102.7, 75.3, 70.6, 60.0, 56.4, 48.1, 41.6, 38.7, 30.1. MS (FAB,
m/z) calcd for C86H87O18 (M þ Hþ) 1407.58, found 1408.4.
Elemental Anal. Calcd for C86H86O18 0.33CHCl3: C, 71.64; H,
3
6.01. Found: C, 71.65; H, 6.30.
1
Supporting Information Available: Copies of H and 13C
NMR spectroscopic data (PDF) and crystallographic analysis
data. This material is available free of charge via the Internet at
http://pubs.acs.org.
8760 J. Org. Chem. Vol. 74, No. 22, 2009