Abundant lattice inclusion phenomenon with sterically hindered and inherently shape-selective tetraarylpyrenes

Article abstract of DOI:10.1021/jo901465f

(Figure Presented) Tetraarylpyrenes H1-H4 that typify molecular systems with orthogonal planes and lack hydrogen bonding functional groups were designed as new host systems with three distinct domains for guest inclusion. In particular, H2 and H4 hosts are found to include a variety of guest molecules. We have determined 42 crystal structures overall (i) to establish the importance of skeletal features of the hosts, (ii) to determine their adaptability in binding diverse guest molecules, and (iii) to delineate favored domains for location of guest molecules and preferred modes of association of the host systems. The unique features of H1-H4 are found to permit binding of aliphatic and aromatic guest species differently: the small-sized guest molecules such as CHCl₃, (CH₃)₂S, etc. are found to be bound in the basin domain, whereas aliphatic and aromatic guests are found to be included in the channel/concave and trough regions, respectively. The crystal structure analyses reveal that as many as 20 out of 28 inclusion compounds of H2 are isostructural with one or more; we have identified 8 different crystal packing types with which each inclusion compound may be associated. The guest-binding potential of host H2 has been exploited to demonstrate the utility of these host systems in (i) the separation of regioisomeric methyl-substituted benzenes and mixtures of cis-trans isomers of decalin, perhydroisoquinoline, and cinnamonitrile, (ii) the stabilization of the keto-enol form of 1,3-diketones, and (iii) the conformational locking of flexible cycloalkanes.

Full text of DOI:10.1021/jo901465f

pubs.acs.org/joc
Abundant Lattice Inclusion Phenomenon with Sterically Hindered and
Inherently Shape-Selective Tetraarylpyrenes
Jarugu Narasimha Moorthy,*,† Palani Natarajan,† and Paloth Venugopalan§
§
†Department of Chemistry, Indian Institute of Technology, Kanpur 208016, India, and Department of
Chemistry, Panjab University, Chandigarh 160 014, India
moorthy@iitk.ac.in
Received July 19, 2009
Tetraarylpyrenes H1-H4 that typify molecular systems with orthogonal planes and lack hydrogen
bonding functional groups were designed as new host systems with three distinct domains for guest
inclusion. In particular, H2 and H4 hosts are found to include a variety of guest molecules. We have
determined 42 crystal structures overall (i) to establish the importance of skeletal features of the hosts,
(ii) to determine their adaptability in binding diverse guest molecules, and (iii) to delineate favored
domains for location of guest molecules and preferred modes of association of the host systems. The
unique features of H1-H4 are found to permit binding of aliphatic and aromatic guest species
differently: the small-sized guest molecules such as CHCl3, (CH3)2S, etc. are found to be bound in the
basin domain, whereas aliphatic and aromatic guests are found to be included in the channel/concave
and trough regions, respectively. The crystal structure analyses reveal that as many as 20 out of
28 inclusion compounds of H2 are isostructural with one or more; we have identified 8 different
crystal packing types with which each inclusion compound may be associated. The guest-binding
potential of host H2 has been exploited to demonstrate the utility of these host systems in (i) the
separation of regioisomeric methyl-substituted benzenes and mixtures of cis-trans isomers of
decalin, perhydroisoquinoline, and cinnamonitrile, (ii) the stabilization of the keto-enol form of
1,3-diketones, and (iii) the conformational locking of flexible cycloalkanes.
Introduction
intermolecular interactions that manifest in certain readily
conceivable synthons.2-4 The creation of organic5 and me-
tal-organic6 porous materials constitutes one of the actively
pursued contemporary themes. An emphasis of interest in
organic materials that functionally mimic inorganic zeolites7
Although crystal structure prediction is not yet possible,1
it is increasingly becoming evident that the molecular pack-
ing can indeed be controlled via exploitation of a wealth of
(1) Dunitz, J. D. Chem. Commun. 2003, 545.
(2) (a) Desiraju, G. R. Crystal Engineering: The Design of Organic Solids;
Elsevier: Amsterdam, The Netherlands, 1989. (b) Crystal Engineering: From
Molecules and Crystal to Materials; Braga, D., Orpan, A. G., Ed.; NATO ASI
Series; Kluwer: Dordecht, The Netherlands, 1999. (c) Design of Organic Solids;
Weber, E., Ed.; Topics in Current Chemistry; Springer: Berlin, 1998; Vol. 198.
(3) (a) Desiraju, G. R. Angew. Chem., Int. Ed. 1995, 34, 2311. (b) Nangia,
A.; Desiraju, G. R. Top. Curr. Chem. 1998, 198, 57.
(4) It appears that the crystal structure can now be predicted from first
principles; see: Newmann, M. A.; Leusen, F. J. J.; Kendrick, J. Angew.
Chem., Int. Ed. 2008, 47, 2427.
8566 J. Org. Chem. 2009, 74, 8566–8577
Published on Web 10/16/2009
DOI: 10.1021/jo901465f
r
2009 American Chemical Society

Moorthy et al.
JOCArticle
is due to their promising applications in gas adsorption,6,8
separation and purification,9 catalysis and asymmetric
synthesis,10 optical resolution,11,12 etc. In a broad sense,
the organic compounds that accommodate guest molecules
can be classified into two categories, “unimolecular”’ and
“multimolecular” inclusion compounds.13 Molecules such as
cyclodextrins, calixarenes, cucurbiturils, crown ethers, cryp-
tands, spherands, etc. with inherent potential to bind guest
molecules constitute excellent examples of unimolecular
inclusion host compounds.14 The multimolecular inclusion
compounds, also termed lattice inclusion host compounds,
differ in the sense that two or more host molecules are
involved in the construction of cavities for guest inclusion;
urea, choleic acids, Dianin’s compound, hydroquinone,
gossypol, etc. are well-known examples of this category.13,15
The chemistry of unimolecular host systems is fairly ad-
vanced.16 However, creation of multimolecular inclusion
compounds with cavities for guest inclusion is challenging
and continues to elicit tremendous interest.8,17
In our recent investigations focused on the development of
functional organic materials,18 we surmised that flat pyrenes
decked up at the four corners with highly rigid aromatic
panels as shown in Scheme 1 should exhibit packing diffi-
culty in the solid state, so that such molecular systems may a
priori be anticipated to crystallize with guest inclusion.19
Indeed, metalated tetraarylporphyrins in which the aryl rings
at meso positions orient orthogonally are well-known to
form inclusion compounds with a variety of guest mole-
cules.20 We reasoned that tetraarylpyrenes should be mark-
edly different from metalated tetraarylporphyrins from
several points of view: (i) whereas tetraarylporphyrins are
of D4h symmetry, tetraarylpyrenes are of reduced D2h sym-
metry, which increases the number of possible packing
modes in the crystal lattice; (ii) tetraarylpyrenes offer three
readily conceivable domains for guest inclusion, namely,
trough, concave, and basin, cf. Scheme 1, to permit inclusion
of two or more guest molecules simultaneously; (iii) the
excellent fluorescence property of tetraarylpyrenes may
permit guest inclusion in the solid state to be signaled via
fluorescence; and (iv) tetraarylpyrenes can be readily
adapted as spacers with unique topology for porous metal-
organic frameworks (MOFs). Thus, we have explored the
guest inclusion behavior of tetraarylpyrenes H1-H4. Here-
in, we report the results of our comprehensive investigations
on the guest inclusion behavior of H1-H4 with a variety of
guest molecules. In particular, the methoxy hosts H2 and H4
are shown to (i) include a number of diverse guest molecules
in all three distinct domains, viz., trough, channel, and basin,
and (ii) exhibit remarkable discrimination in the binding of
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J. Org. Chem. 2004, 69, 1762. (o) Laliberte, D.; Maris, T.; Wuest, J. D. J. Org.
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12119. (b) Endo, K.; Sawaki, T.; Sawaki, T.; Koyanagi, M.; Kobayashi, K.;
Masuda, H.; Aoyama, Y. J. Am. Chem. Soc. 1995, 117, 8341. (c) Ung, A. T.;
Gizachew, D.; Bishop, R.; Scudder, M. L.; Dance, I. G.; Craig, D. C. J. Am.
Chem. Soc. 1995, 117, 8745. (d) Janiak, C. Angew. Chem., Int. Ed. 1997, 36,
1431. (e) Sawaki, T.; Aoyama, Y. J. Am. Chem. Soc. 1999, 121, 4793.
(f) Goldberg, I. Chem.;Eur. J. 2000, 112, 3863. (g) Malek, N.; Maris, T.;
Perron, M.-E.; Wuest, J. D. Angew. Chem., Int. Ed. 2005, 44, 4021.
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Angew. Chem., Int. Ed. 2005, 44, 1816.
(15) (a) Gdaniec, M.; Ibragimov, B. T.; Talipov, S. A. Gossypol. In Compre-
hensive Supramolecular Chemistry; Macnicol, D. D., Toda, F., Bishop, R., Eds.;
Elsevier Sciences: London, 1996; Vol. 6, p 117. (b) Gossypol: Ibragimov, B. T.;
Talipov, S. A. Encyclopedia of Supramolecular Chemistry; Marcel Decker: New
York, 2004; p 606. (c) Miyata, M.; Tohnai, N.; Hisaki, I. Molecules 2007, 12,
1973.
(16) (a) Encyclopedia of Supramolecular Chemistry; Atwood, J. L., Steed,
J. W., Eds.; Marcel Decker: New York, 2004; Vols. I and II. (b) Goldberg, I. In
Inclusion compounds; Atwood, J. L., Davies, J. E. D., Macnicol, D. D., Eds.:
Oxford University Press: Oxford, 1991; Vol. 4; p 406.
(9) Separation and Reactions in Organic Supramolecular Chemistry; Toda,
F., Bishop, R., Eds.; Wiley: New York, 2004.
(10) (a) Macnicol, D. D., Toda, F., Bishop, R., Eds. Comprehensive Supra-
molecular Chemistry, Solid State Chemistry: Crystal Engineering; Pergamon
Press: Oxford, 1996. (b) Desiraju, G. R. Curr. Opin. Solid. State. Mater. Sci.
1997, 2, 451. (c) Heath, J. R., Ed. Acc. Chem. Res. 1999, 32, 388 (special issue on
Nanoscale Materials). (d) Perspectives in Supramolecular Chemistry; Supra-
molecular Materials and Technologies; Reinhoudt, D. N., Ed.; Wiley: Chiche-
ster, 1999. (e) Miyata, M.Inclusion Reactions and Polymerization.Encyclopedia
of Supramolecular Chemistry; Marcel Decker: New York, 2004; p 705.
(f) Ramamurthy, V. Photochemistry in Constrained and Organized Media;
VCH Publishers: New York, 1991. (g) Rebek, J., Jr. Acc. Chem. Res. 1999, 32,
278.
(11) Toda, F. Pure Appl. Chem. 2001, 73, 1137 and references therein.
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(b) Hertzsch, T.; Budde, F.; Weber, E.; Hulliger, J. Angew. Chem., Int. Ed.
2002, 41, 2282.
(13) (a) Molecular Inclusion and Molecular Recognition-Clathrates I and II.
In Topics in Current Chemistry; Weber, E., Ed.; Springer-Verlag: Berlin-
Heidelberg; 1987 and 1988; Vols. 140 and 149. (b) Bishop, R. Chem. Soc. Rev.
1996, 311.
(17) (a) MacGillivray, L.; Atwood, J. L. J. Am. Chem. Soc. 1997, 119,
6931. (b) Nangia, A. Cryst. Growth Des. 2008, 8, 1079. (c) Bhogala, B. R.;
Nangia, A. New J. Chem. 2008, 32, 800. (d) Hisaki, I.; Shizuki, N.; Aburaya,
K.; Katsuta, M.; Tohnai, N.; Miyata, M. Cryst. Growth Des. 2009, 9, 1280.
(e) Jacob, T.; Lloyd, G. O.; Bredenkamp, W.; Barbour, L. J. Cryst. Growth
Des. 2009, 9, 1284.
(18) (a) Natarajan, R.; Savitha, G.; Dominiak, P.; Wozniak, K.;
Moorthy, J. N. Angew. Chem., Int. Ed. 2005, 44, 2115. (b) Natarajan, R.;
Savitha, G.; Moorthy, J. N. Cryst. Growth Des. 2005, 5, 69. (c) Moorthy,
J. N.; Natarajan, P.; Venkatakrishnan, P.; Huang, D.-F.; Chow, T. J. Org.
Lett. 2007, 9, 5215. (d) Moorthy, J. N.; Venkatakrishnan, P.; Huang, D.-F.;
Chow, T. J. Chem. Commun. 2008, 2146. (e) Moorthy, J. N.; Venkatakrishnan,
P.; Natarajan, P.; Huang, D.-F.; Chow, T. J. J. Am. Chem. Soc. 2008, 130,
17320.
(19) Our extensive search of the Crystal Structure Database (ConQuest
Ver-1.11, CCDC-2009) revealed only 6 structures of tetraalkyl/arylpyrenes
(ref codes: GANQES, MEBZID, MEBZOJ, WENJUV, COBDAZ,
HIZBUO). Only in one case, i.e., 1,3,6,8-tetrakis(4-methoxyphenyl)pyrene
(GANQES), was inclusion of THF observed. Notably, no systematic in-
vestigations as to the phenomenon of guest inclusion by pyrenes have
heretofore been reported to the best of our knowledge.
(20) (a) Byrn, M. P.; Curtis, C. J.; Hsiou, Y.; Khan, S. I.; Sawin, P. A.;
Tendick, S. K.; Terzis, A.; Strouse, C. E. J. Am. Chem. Soc. 1993, 115, 9480.
(b) Goldberg, I. Porphyrin-Based Clathrates. Encyclopedia of Supramolecular
Chemistry; Marcel Decker: New York, 2004; p 1150.
(14) (a) Inclusion Compounds; Atwood, J. L., Davies, J. E. D., Macnicol,
D. D., Eds.; Academic Press Inc.: London, 1984. (b) Inclusion Compounds;
Atwood, J. L., Davies, J. E. D., Macnicol, D. D., Eds.; Oxford University Press:
Oxford, 1991. (c) Comprehensive Supramolecular Chemistry; Atwood, J. L.,
Davies, J. E. D., MacNicol, D. D., Vogtle, F., Lehn, J.-M., Eds.; Pergamon:
Oxford, 1996.
J. Org. Chem. Vol. 74, No. 22, 2009 8567

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SCHEME 1. Molecular Structures of Hosts H1-H4, Half Components H5 and H6, and Cartoon Drawing That Typifies
Hosts H1-H4
SCHEME 2. Synthetic Routes for Inclusion Hosts H1-H4 and the Half Components H5 and H6
stereo- and regioisomeric mixtures. In addition to separation,
their utility is demonstrated in freezing conformationally
flexible molecules in one/two of their conformation/s and
trapping of one of the tautomeric forms from an equilibrium
mixture of keto-enol and 1,3-diketone forms.
TABLE 1. Comparison of H:G Stoichiometries and Guest-Accessible
Volumes for Inclusion Compounds of H1, H2, and H4 with Common
Aliphatic and Aromatic Guest Moleculesa
H1
H2
H4
guest
H:G
V (%)
H:G
V (%)
H:G
V (%)
decalin
1:2
1:2
1:1
1:0.5
38
48
13
12
1:1
1:2
1:2
1:2
25
50
28
36
1:4
1:3
1:2
46
56
21
dodecene
benzene
mesitylene
Results and Discussion
Synthesis of Host Pyrenes H1-H4. The synthesis and
characterization of host pyrenes H1 and H2 have already
been published by us in the context of their application in
organic light emitting diodes (OLEDs).18c The hosts H3 and
H4 were similarly prepared via Suzuki coupling protocol by
employing 4-isopropoxy-2,6-dimethylphenylboronic acid
and 4-methoxymethyl-2,6-dimethylphenylboronic acid, re-
spectively, Scheme 2. A similar protocol was employed
for the synthesis of H5 and H6 using dibromo-substituted
m-xylene and 1,3-dimethoxybenzene; see Supporting Infor-
mation.
Guest Inclusion Behavior of Hosts H1-H4. Initial crystal-
lization experiments with hosts H1-H4 in the presence of
simple aliphatic and aromatic guest molecules revealed that
the former exhibit solid-state guest inclusion behavior, as
revealed by 1H NMR and X-ray structural analyses of some
crystals. More critical analyses were performed for hosts H1,
aH:G = host/guest ratio; V = guest-accessible volume.
H2, and H4 with some common guest molecules.21 To gauge
the relative abilities of these host systems in particular, X-ray
determined structures of the inclusion compounds with two
aliphatic and two aromatic guest molecules were analyzed
for host:guest ratios, and the guest-accessible volumes were
calculated by the program “PLATON”. These data collated
in Table 1 clearly show that H4 is far superior to H1 and H2
and that the latter is comparatively better than H1. On
the basis of the consideration that the methoxy groups in
(21) CCDC
726009-726023,
726028-726030,
726970-726973,
726976-726978, 726980-726985 and 726987-726997 contain the supple-
mentary crystallographic data for H2, H4-H6 and all of the inclusion
compounds of H1-H4. These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
8568 J. Org. Chem. Vol. 74, No. 22, 2009

Moorthy et al.
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TABLE 2. Various Guests That are Bound by Hosts H1-H4 and Host:Guest Ratios of the Inclusion Compounds
host
guest molecules (host:guest)
H1
H2
cyclododecene (1:2), decalin (1:2), benzene (1:1), mesitylene (1:0.5)
dimethyl sulfide (1:2), CHCl3 (1:2), CCl4 (1:2), dichloroethane (1:2), acetylacetone (1:2), THF (1:2), chlorocyclohexane (1:4),
bromocyclohexane (1:4), 2-cyclohexen-1-one (1:2), cyclooctane (1:4), cyclodecane (1:1), cyclododecene (1:2.5),
dicyclopentadiene (1:3), decalin (1:1), perhydroisoquinoline (1:1), benzene (1:2), toluene (1:1), phenylacetylene (1:2),
benzonitrile (1:1), nitrobenzene (1:2), cinnamonitrile (1:2), o-xylene (1:2), p-xylene (1:2), mesitylene (1:2), biphenyl (1:4),
diphenyl ether (1:1), naphthalene (1:2), p-terphenyl (1:2)
H3
H4
p-xylene (1:3)
cyclododecene (1:3), decalin (1:4), benzene (1:2), benzonitrile (1:1), pyrene (1:1)
TABLE 3. Crystal Data for Representative Inclusion Compounds of H2 with Various Guests
H2 chloroform
3
H2 decalin
H2 cyclooctane
3
H2 benzonitrile
3
3
C62H68O4
formula
FW
crystal system
space group
C54H52Cl6O4
977.89
orthorhombic
Pbca
C84H114O4
1187.75
monoclinic
C2/c
C119H109N2O4
1696.43
monoclinic
C2/c
877.16
monoclinic
P21/n
˚
a (A)
17.706(2)
11.613(1)
25.186(1)
90.0
90.0
90.0
7.3082(2)
14.4393(2)
23.831(1)
90.0
97.946(2)
90.0
36.839(2)
10.456(2)
21.481(1)
90.0
122.196(2)
90.0
20.637(3)
21.858(3)
22.694(3)
90.00
108.444(4)
90.00
˚
b (A)
˚
c (A)
R (deg)
β (deg)
γ (deg)
V (A )
Z
F(000)
GOF
final R1
final wR2
host:guest
3
˚
5179(4)
4
2040
2490.6(1)
2
944
7002(2)
4
2600
9711(2)
4
3808
1.019
0.0794
1.061
1.034
1.046
0.0895
0.2471
1: 2
0.0744
0.1873
1:1
0.0787
0.2022
1: 4
0.1976
1: 1
H2 mesitylene
H2 dichloroethane
H2 naphthalene
H2 cinnamonitrile
3
3
3
3
formula
FW
C70H74O4
979.29
monoclinic
P21/c
12.9180(1)
15.7692(2)
14.2495(1)
90.0
C56H58Cl4O4
936.82
monoclinic
P21/c
7.8862(2)
21.289(1)
15.369(1)
90.0
C72H66O4
995.25
monoclinic
P21/n
14.227(2)
14.854(3)
14.478(3)
90.0
C70H64N2O4
997.23
orthorhombic
Pna21
19.600(2)
9.8101(1)
28.415(4)
90.0
crystal system
space group
˚
a (A)
˚
b (A)
˚
c (A)
R (deg)
β (deg)
γ (deg)
106.017(1)
90.0
95.306(1)
90.0
117.304(3)
90.0
90.0
90.0
3
˚
V (A )
Z
2790.0(1)
2
1052
2569.3(1)
2
988
2718.8(8)
2
1060
5475.0(1)
4
2120
F(000)
GOF
1.030
1.023
1.087
1.035
final R1
final wR2
host:guest
0.0546
0.1282
1: 2
0.0615
0.1470
1: 2
0.0896
0.2113
1: 2
0.0528
0.1217
1: 2
H2 may contribute to lattice stabilization via possible
C-H O and C-H π interactions,22 we rigorously
analogous hosts H1, H3, and H4 are discussed briefly to
exemplify the novelty associated with the structural attri-
butes of all hosts. Also discussed are the crystal structures of
H5 and H6, which represent approximately the half compo-
nents of hosts H1 and H2, respectively.
Lattice Inclusion Compounds of H2. In Table 2 are shown
diverse guest molecules with which the host H2 was crystal-
lized readily as a solid material by slow evaporation of its
solution in the neat guest itself (when the guest is a liquid) or
its solution in chloroform in the presence of the guest.23
3 3 3
3 3 3
examined the potential of host H2 to include a variety of
guest molecules and demonstrate the functional utility
of such host systems. In Table 2 are consolidated a variety
of guest molecules with which the inclusion compounds of
H1-H4 were formed. Also, the host:guest ratios for all
inclusion compounds are indicated in parentheses.
In the following, we shall first consider the abundant
lattice inclusion phenomenon observed for H2, various
modes in which it includes diverse guest molecules and
isostructurality of several of its inclusion compounds.21
Subsequently, the inclusion phenomena observed for
(23) Although host H2 crystallizes itself by including CHCl3, the inclu-
sion of added guests was preferably observed. The preferential inclusion of an
added guest in a solvent that itself acts as a guest is well known; for example,
see: Nakano, K.; Mochizuki, E.; Yasui, N.; Morioka, K.; Yamauchi, Y.;
Kanehisa, N.; Kai, Y.; Yoswathananont, N.; Tohnai, N.; Sada, K.; Miyata,
M. Eur. J. Org. Chem. 2003, 2428.
(22) Desiraju, G. R.; Steiner, T. The Weak Hydrogen Bond In Structural
Chemistry and Biology; Oxford University Press: Oxford, 1999.
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JOCArticle
TABLE 4. Isostructural Inclusion Compounds of H2 with Various Guest Molecules and Their Space Groups
entry
guest compounds
packing type
space group
1
2
3
4
5
6
7
chloroform and carbon tetrachloride
1
2
3
4
5
6
7
Pbca
P21/n
C2/c
cyclodecane, decalin, and perhydroisoquinoline
chlorocyclohexane, bromocyclohexane, and cyclooctane
2-cyclohexen-1-one and benzonitrile
acetylacetone, benzene, nitrobenzene, p-xylene, mesitylene, and p-terphenyl
1,2-dichloroethane and cyclododecene
phenylacetylene and naphthalene
C2/c
P21/c
P21/c
P21/n
FIGURE 1. Molecular structures of the inclusion compounds of host H2 with chloroform and THF (a and b), trans-decalin and cyclodecane
(c and d), and trans-cinnamonitrile and biphenyl (e and f). Notice that the guests sit in the basin of the host in the top row and in the concave and
trough regions in the middle and bottom rows, respectively.
Crystallization of H2 alone in ethyl acetate yielded guest-free
crystals (vide infra). The crystal structures of the inclusion
compounds of H2 with all of the guest molecules in Table 2
were determined by X-ray crystallography. The details of
crystal data and structure determination for representative
inclusion compounds are given in Table 3; these details for
others are provided in Supporting Information. In most
cases, the guest inclusion was independently established by
TGA, 1H NMR spectroscopy, and PXRD analyses; see
Supporting Information.
As mentioned earlier, the host design features three dis-
tinct domains in which the guest molecules may be included
in the crystal lattice. The analyses of X-ray determined
crystal structures of the inclusion compounds unambigu-
ously establish the inclusion of guest molecules in all three
domains of the host as presupposed. In Figure 1 are shown
8570 J. Org. Chem. Vol. 74, No. 22, 2009

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FIGURE 2. Structures of the inclusion compounds of H2 with naphthalene (a), cyclododecene (b), cyclooctane (c), and chlorocyclohexane (d).
the molecular structures of H2 with chloroform, THF, trans-
decalin, cyclodecane, cinnamonitrile, and biphenyl.
of these types. The locations of guests in these packing modes
are shown by an elliptical solid.
Remarkably, the small guest molecules such as dimethyl
sulfide, chloroform, CCl4, and THF were found to be located
in the basin region of the host H2, while aromatic guests such
as cinnamonitrile and biphenyl were found to be located in
troughs. Aliphatic guest molecules such as cyclodecane,
decalin, and perhydroisoquinoline were found to be included
in the concave domain of the host H2. Of course, some guest
molecules were found to occupy two domains at the same
time. For example, cyclooctane and chlorocyclohexane oc-
cupy the basin and concave domains, and naphthalene
and cyclododecene are found in both trough and concave
regions as shown in Figure 2.
As the inclusion of guest molecules with diverse structures
must occur via different modes of association of the host H2,
we have examined the crystal packings of all compounds to
identify preferred modes of association of the hosts that
augment guest inclusion. The fact that the host H2 undergoes
crystal packing in certain preferred ways is suggested by the
isostructurality observed for several of its compounds with
different guests. The compounds that exhibit isostructurality
are given in Table 4; as many as 20 out of 28 inclusion
compounds of H2 are found to be isostructural with two or
more compounds. By reducing the host structure to a
cartoon consisting of a rectangle joined at the vertices by
solid lines, the crystal structures of 28 inclusion compounds
of H2 were analyzed to discern common modes of packing
among themselves. In all, 8 different types were identified in
which the host molecules were found to organize by includ-
ing the guest molecules in the crystal lattices. These 8 types of
association of the host H2 are shown in Figure 3. In essence,
almost all inclusion compounds may be associated with one
Self-Inclusion of Guest-Free Host H2. Host H2 was found
to crystallize readily from its solution in ethyl acetate in its
guest-free state. The crystals were found to belong to P21/c
space group with two distinct molecules (half each in the
asymmetric unit) A and B lying on the crystallographic inver-
sion centers. In Figure 4 are shown typical crystal packing
diagrams. A careful inspection of the crystal packing reveals
that the molecules of type A are connected via C-H
π
3 3 3
interactions22 between the methoxy methyl hydrogens and the
central pyrene rings to form squares, within which the mole-
cules of type B are located; see Supporting Information. By
positioning the dimethylanisyl rings into the trough regions of
molecules A, the molecules B function as guests in a manner
that the crystal system may be viewed as a case of self-inclusion
as shown in Figure 4. Indeed, a comparison of the crystal
packing with those of its inclusion compounds with acetyl
acetone, benzene, toluene, nitrobenzene, o-xylene, p-xylene,
mesitylene, and p-terphenyl leads to the compelling inference
that guest-free modification truly represents a case of self-
inclusion. It is only recently that Barbour et al. have docu-
mented precedence for such a scenario.24
Isostructurality of Inclusion Compounds of H2. Isostruc-
turality refers to identical crystal packings. In the context of
host-guest chemistry, the isostructurality refers to similar
organization of host molecules. The isostructural lattice
inclusion compounds are believed to present a unique
(24) Lloyd, G. O.; Alen, J.; Bredenkamp, M. W.; De Vries, E. J. C.;
Esterhuysen, C.; Barbour, L. J. Angew. Chem., Int. Ed. 2006, 45, 1.
(25) (a) Isostructurality: Caira, M. R. Encyclopedia of Supramolecular
Chemistry; Marcel Decker: New York, 2004; p 767. (b) Cincic, D.; Friscic, T.;
Jones, W. Chem.;Eur. J. 2008, 14, 747.
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Moorthy et al.
JOCArticle
FIGURE 3. Various modes of association of host H2 and vacant spaces that the guest molecules occupy (shown with solid ellipses). Also
indicated are the guests whose inclusion compounds belong to the corresponding type. Type 1: dimethyl sulfide, chloroform, carbon
tetarchloride, and tetrahydrofuran. Type 2: cyclodecane, decalin and perhydroisoquinoline. Type 3: chlorocyclohexane, bromocyclohexane
and cyclooctane. Type 4: 2-cyclohexen-1-one, benzonitrile, diphenyl ether and dicyclopentadiene. Type 5: acetylacetone, benzene, toluene,
nitrobenzene o-xylene, p-xylene, mesitylene and p-terphenyl. Type 6: dichloroethane and cyclododecene. Type 7: phenylacetylene and
naphthalene. Type 8: biphenyl and cinnamonitrile.
opportunity to investigate structure property relation-
ships.25 For example, analysis of the loss of guest molecules
thermally in isostructural compounds may benefit us with
the knowledge of distinct thermodynamic and kinetic
parameters, which may be intimately connected with the
host-guest interplay.
As shown in Table 4, 20 structures out of 28 inclusion
compounds of H2 are isostructural. Aside from the adapt-
ability, which seemingly confers the host system with flexi-
bility to explore diverse crystal packings, cf. Table 2, most
packing types being common to one or more inclusion
compounds reflects appreciable preference of the host sys-
tem to adopt certain limited packing modes frequently.
Thus, the analysis of the crystal packings of a large number
of inclusion compounds with varying guests may permit the
prediction of the crystal packing of an inclusion compound
with a given guest. For example, we were guided in our initial
studies by the isostructurality of H2 benzene, H2 nitro-
3
3
benzene, and H2 mesitylene to determine the structures of
3
H2 p-xylene and H2 p-terphenyl. The latter were indeed
3
3
found to be isostructural to those of H2 benzene,
3
H2 nitrobenzene, and H2 mesitylene (Table 4 and Support-
3
3
ing Information). In a similar manner, H2 cyclodecane was
3
initially anticipated to be isostructural to those of H2
decalin and H2 perhydroisoquinoline, and this was indeed
found to be so.
3
3
8572 J. Org. Chem. Vol. 74, No. 22, 2009

Moorthy et al.
JOCArticle
FIGURE 5. Crystal packing diagram of H3 p-xylene and its car-
toon representation (right).
3
FIGURE 4. Crystal packing of H2 down the a- and b-axes. The two
different molecules in the asymmetric unit cell are shown in different
colors.
formed with aliphatic guest molecules such as cyclododecene
and trans-decalin and aromatic guest molecules such as
benzene, benzonitrile, and pyrene (Supporting Information).
Of course, the host H4 was found to selectively include the
trans-isomer of decalin when the crystallization was carried
out in the presence of a mixture of cis and trans isomers.
Notably, the H4 was also found to crystallize in its guest-free
form (monoclinic, P21/n).
The crystal packing of the inclusion compounds of H4
with cyclododecene and decalin were found to be similar to
those of the compounds with host H2; they correspond to the
patterns typified by type 3 and type 2 (Figure 3). Likewise,
the organization of aromatic guest molecules such as
benzene, benzonitrile, and pyrene were found to be similar
to those of the inclusion compounds of H2 corresponding to
types 2, 1, and 8, respectively.
Inclusion Compounds of Host H1. The inclusion compounds
of H1 with aliphatic and aromatic guest molecules such as
cyclododecene, decalin, benzene, and mesitylene were grown
readily from the solutions of H1 in chloroform containing the
added guest. The crystals of inclusion compounds formed with
decalin, cyclododecene and benzene were found to correspond
to a triclinic system (P-1), while those with mesitylene belonged
to a monoclinic crystal system (P2/n).
The crystal packings of the inclusion compounds of H1
with cyclododecene and decalin were found to be similar to
those of the respective inclusion compounds with host H2
(see Supporting Information); they correspond to the
pattern typified by type 3, Figure3. Likewise, the organization
of aromatic guest molecules such as benzene and mesitylene
are found to be similar to those in the inclusion compounds of
H2 corresponding to types 3 and 1, respectively.
As mentioned previously, simple comparison of the struc-
tures of the inclusion compounds of H2 and H4 with
common guest molecules, namely, decalin, dodecene, ben-
zene, and mesitylene, points to considerable flexibility of H4
(Table 1). For decalin as the guest, the host:guest ratio is 1:4
for H4, whereas it is 1:1 for H2; the guest-accessible volume
in the inclusion compound of H4 is 46% and for H2 it is ca.
25%. In contrast, for guest molecules such as dodecene, both
H2 and H4 exhibit comparable host:guest ratios and void
volumes. Otherwise, the fact that H4 can exhibit highly flexible
guest-dependent crystal packing is compellingly evident.
Crystal Structure of H5 and H6. To illustrate the fact that
the skeletal features intrinsic to hosts H1-H4 are important
in determining their inclusion property, we synthesized
model compounds H5 and H6. The latter can be considered
half components of pyrene hosts H1 and H2 and are bereft of
the central core skeleton. The methyl and methoxy groups
were meant to ensure that the mesityl and dimethyl-p-anisyl
rings in H5 and H6 lie orthogonally to the central benzene
ring such that the trough domain in host pyrenes H1-H4 is
replicated. Several attempts to obtain inclusion compounds
of these systems with a variety of aliphatic as well as aromatic
guest molecules were in vain. In all attempts, the crystals that
gave unique cell dimensions were obtained. The X-ray
structure determinations revealed that the crystals of H5
and H6 were devoid of any guest inclusion (Supporting
Information). Indeed, it is noteworthy that both H5 and
H6 were found to be isostructural, despite considerable
differences in terms of the substituents present in each.
Flexibility of Hosts H1-H4. It is amply evident from a
comparison of the behavior of hosts H1-H4 with those of
H5 and H6 that the unique structural features inherent to
hosts H1-H4 are responsible for the remarkable inclusion
behavior exhibited by them. The inclusion behavior cannot
be said to arise solely from packing difficulties, as the hosts
Inclusion Compounds of Host H3. Although the host H3
was found to include aromatic guest molecules readily, the
crystals were found to be either too thin or were found to lose
the guest molecules instantaneously when removed from the
mother liquor. We were successful in determining the crystal
structure of the compound with guest p-xylene, whose crystal
packing is shown in Figure 5. The crystals of H3 p-xylene were
3
found to belong to triclinic crystal system (space groupP-1); see
Supporting Information. The asymmetric unit cell was found to
contain one host and three guest molecules such that H3:guest
ratio is 1:3. In the crystal lattice, the host molecules lie in the
bc-plane with an angle of inclination and interact via
C-H O hydrogen bonds with the molecules that are related
3 3 3
by inversion symmetry (along the c-axis) and translation
symmetry (along the b-axis). The guest p-xylene molecules are
found to be located in both trough and concave domains of the
host pyrene structure. The PLATON calculation reveals that
the guest-accessible volume is approximately 40%.
Inclusion Compounds of Host H4. The objective in synthe-
sizing the host H4 was to examine if structural expansion by
changing the methoxy to methoxy methyl group manifests in
increased void spaces for guest inclusion. The consequences
of introduction of a methylene group include (i) change
of hybridization of the oxygen from sp2 in H2 to sp3 in H4,
(ii) increased flexibility of the methoxy oxygen to participate in
weak intermolecular interactions22 and (iii) elongation of the
aryl ring structurally so that even large molecules could possibly
be bound. So, modified behavior toward guest inclusion was
expected, while similar mode of inclusion as that of H2 with
some guest species was not deemed surprising.
The host H4 was found to exhibit inclusion property
similar to those of all other analogues. It was found to bind
both aliphatic as well as aromatic guest molecules. We have
determined the crystal structures of the inclusion compounds
J. Org. Chem. Vol. 74, No. 22, 2009 8573

Moorthy et al.
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H2 and H4 also crystallize in their guest-free forms.26
The host pyrenes seemingly enjoy considerable packing
flexibility to exhibit highly guest-dependent inclusion beha-
vior. From where do the hosts H1-H4 derive their packing
flexibility?
Insofar as the intermolecular interactions are concerned,
all inclusion compounds H1-H4 are devoid of any strongly
interacting functional groups that may decisively control the
crystal packing. A careful analysis of intermolecular inter-
actions suggests that the inclusion compounds are stabilized
compound of H2 with dimethyl sulfide, complete exclusion of
the guest was found to occur at ca. 75 °C. Clearly, the
host-host and host-guest interactions manifest in stronger
binding of the guest molecules to reduce their volatility.22
Separation of Structural Isomers. One of the pressing
problems in chemical industry is the separation of isomers
with a very marginal difference in their boiling points.9,13 Of
particular relevance is the separation of regioisomers of di-
methylbenzenes, namely, xylenes. We found that the host H2
independently binds all three isomers when crystallized sepa-
rately. However, when H2 was crystallized in the presence of
an equimolar mixture of the three isomers, only p-xylene was
found to be selectively included as revealed by 1H NMR and
PXRD analyses of the isolated crystals (eq 1).23 The host:guest
stoichiometry was found to be 1:1. The crystal packing, shown
in Figure 3, reveals that the guest molecules are located in the
trough domain of the host structure, type 5. In a similar
manner, 1,3,5-trimethylbenzene was selectively bound by H2
when the crystallization was carried out in an equimolar
mixture of 1,2,3-, 1,2,4-, and 1,3,5-trimethylbenzenes (eq 2).
The selective inclusion of the 1,3,5-isomer was independently
by weak C-H O and C-H π interactions between
3 3 3 3 3 3
host-host and host-guest molecules.22 Although sterics
due to the methyl groups are expected to render the aryl
rings orthogonal to the flat pyrene ring, we wondered if
their orientations are disturbed in pursuit of guest bind-
ing. In other words, do the aryl rings exhibit some flex-
ibility in their orientations to adopt structures that
are complementary to the guests for binding? We have
critically examined the angles between the aryl rings and
the central pyrene ring in all 42 compounds for which the
structures have been determined in the present investiga-
tion. The angles are found to vary by ca. 20°, with the
lowest being 68.10° and the highest being 89.90°
(Supporting Information). This is evidently a large
enough window for the aryl rings to exhibit orientational
flexibility, which may confer the host systems with the
incentive to adopt structures in accordance to the shapes
of the guest molecules. Further, the flexible methoxy and
methoxymethyl groups in H2 and H4 may contribute to
guest binding by positioning themselves in an appropriate
manner. Of course, the fact that all compounds crystallize
in centrosymmetric space groups suggests that the crystal-
lographic symmetry supposedly imposes certain restric-
tions on the geometries found.
1
established by H NMR and PXRD analyses of the isolated
crystals as in the case of the H2 p-xylene compound. Indeed,
3
the crystal packing of H2 1,3,5-trimethylbenzene is akin to
3
that of the inclusion compound of H2 p-xylene (Supporting
Information).
3
The inclusion phenomenon driven by conformational
flexibility and inherent topological features is akin to con-
formational polymorphism being uncovered in recent
times.27 The presently described structures compellingly
demonstrate how the conformational flexibility when com-
bined with molecular attributes may be elegantly exploited
for host-guest phenomena.
Applications of Hosts H1-H4. The remarkable inclusion
behavior of the hosts H1-H4 prompted us to explore their
utility to (i) achieve separation of closely related structural
isomers, (ii) trap organic volatile molecules in the crystal
lattice, (iii) freeze out one of the equilibrium tautomeric
forms of a 1,3-diketone, and (iv) trap conformationally
flexible cyclic molecules in one/two of their conformations.
In particular, we have employed the methoxy-pyrene H2 to
demonstrate each of the aforementioned objectives.
Trapping of Volatile Organic Molecules. The inclusion
phenomenon may modify volatility of the guest molecules.13
The host H2 was found to readily form crystals with low
boiling solvents such as dimethyl sulfide (bp = 38 °C),
CHCl3 (bp = 61 °C), and CCl4 (bp = 76 °C). The TGA
analyses reveal that the guest molecules are released at
temperatures 10-20 °C higher than their respective boiling
points (Supporting Information). For the case of the inclusion
The difference in the boiling points of cis and trans isomers of
cinnamonitrile is very marginal, and the commercially available
compound is generally a mixture. Crystallization of H2 in
CHCl3 with an added mixture (40:60) of cis- and trans-cinna-
monitrile led to crystals containing exclusively the trans isomer
(eq 3). As in the earlier case, this was verified by 1H NMR and
PXRD analyses (Supporting Information). Here again, the
(26) We have not deliberately attempted to crystallize H1 and H3 in their
guest-free states. In the absence of any such effort, there is no reason to
believe that they will not crystallize without guest molecules.
(27) Nangia, A. Acc. Chem. Res. 2008, 41, 595.
8574 J. Org. Chem. Vol. 74, No. 22, 2009

Moorthy et al.
JOCArticle
guest is found to occupy the trough domain of the host
(Figure 1).
form (Supporting Information and eq 5). The guest is
found to occupy the trough region of the host with a
C-H O hydrogen bond (between C2H of pyrene and
3 3 3
the oxygen atom of the guest enol) primarily playing the
binding force; of course, the shape of the guest is also
important in filling the vacant space. The crystal packing
of H2 acetylacetone is similar to those of the inclusion
3
compounds of H2 with benzene, toluene, nitrobenzene, o-
xylene, p-xylene, mesitylene, and p-terphenyl shown in
Figure 3. It is noteworthy that the enol form has been
trapped in four lattice inclusion hosts so far.29 It turns out
that acetylacetone is hydrogen-bonded to the host mole-
The cis and trans isomers of decalin and perhydroisoquino-
line constitute excellent examples of aliphatic guest molecules
with a very low difference in their boiling points. The host H2
was found to crystallize in each case with the trans isomer,
when the crystallization was carried out in the presence of a
mixture (52:48) of cis- and trans-decalin/perhydroisoquinoline
(eq 4). The structures of H2 trans-decalin and H2 trans-
cules via O-H O hydrogen bond in all of these cases,
3 3 3
unlike in the present scenario where it is C-H O hydro-
3 3 3
gen bonded to the nonpolar host molecule.
3
3
perhydroisoquinoline are isostructural, and the host:guest
stoichiometry is 1:1. In contrast to aromatic guest mole-
cules discussed above, the trans-fused decalin molecules
are found in the concave domains of the host. The fact that
the crystals grown uniformly contained the trans-isomer
was established by combining 1H NMR with GC as well as
PXRD analyses of the bulk sample. The crystal packing is
shown in Figure 3 for the case of H2 trans-decalin. The
3
Freezing of Flexible Molecules in Dynamic Conformational
Equilibrium. One of the fascinating applications of hos-
t-guest inclusion chemistry is the isolation of liquid samples
as crystalline materials at room temperature. This protocol
has traditionally inspired chemists to gain exciting X-ray
structural insights concerning compounds that are otherwise
liquids.12,13 Crystallization of H2 in 1,2-dichloroethane led
to inclusion crystals of the solvent molecules (Table 2). The
conformation of 1,2-dichloroethane was found to be anti
(Supporting Information). It turns out that the anti confor-
mation does indeed correspond to the lowest energy, while
gauche corresponds to the higher energy form.30 In a similar
manner, both chloro- and bromocyclohexanes were found to
be included by the host H2. The X-ray structural investiga-
tions reveal that both compounds exhibit isostructurality
with chloro/bromo exchange bringing about no change in
the crystal packing. In both structures, the halogen is found
to occupy the equatorial position (eq 6).31
crystal structure analyses reveal virtually no interactions
between the host and guest molecules. It appears that the
structural (shape) complementarity is the riding factor in
determining the guest inclusion and hence the crystal
formation. We have found that the host molecules H1
and H4 also include selectively the trans isomer; in the case
of H4, however, the expanded structure permits inclusion
of two guest molecules in the asymmetric unit cell such
that the host:guest stoichiometry is 1:4 (Supporting
Information).
Trapping of Keto-Enol Form of 1,3-Diketones. In general,
1,3-diketones exist in equilibrium with their keto-enol
forms, whose relative concentrations are determined
by the solvent characteristics. There have been early
attempts to trap either of the two forms exclusively by
host:guest chemistry. While the early reports appear to
be irreproducible,9 Toda et al. showed that acetylacetone
is included in the crystal lattices of 1,1,-di(p-hydroxy-
phenyl)cyclohexane and (R,R)-(-)-trans-4,5-bis(hydroxy-
diphenylmethyl)-2,2-dimethyl-1,3-dioxacyclopentane (Taddol)28
in its keto-enol form. In our experiments, we found that
acetylacetone readily gets incorporated in the lattice of
H2, when the crystallization of the latter is carried out in
CHCl3 containing acetylacetone. The X-ray crystal
structure reveals that the guest is trapped in its keto-enol
Various possible conformations with marginally varying
energies are theoretically possible for cyclooctane and cyclo-
decane as shown in Figure 6. The host H2 was found to freeze
(29) (a) Gallardo, O.; Csoeregh, I.; Weber, E. J. Chem. Crystallogr. 1995,
25, 769. (b) Camerman, A.; Mastropaoto, D.; Camerman, N. J. Am. Chem.
Soc. 1983, 105, 1584.
(28) Lipkowska, Z. U.; Yoshizawa, K.; Toyota, S.; Toda, F. CrystEng-
Comm 2003, 5, 114.
(30) Sidhu, P. S.; Enright, G. D.; Ripmeester, J. A. J. Phys. Chem. B 2002,
106, 8569.
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Moorthy et al.
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FIGURE 6. Various low-energy conformations of cyclooctane (left) and cyclodecane (right). Also shown are the conformations that are found
in their inclusion compounds with H2.
cyclooctane in its chair-boat and boat-boat conforma-
tions (the asymmetric unit cell contains 2 molecules of
cyclooctane). The more flexible cyclodecane was found to
be trapped in H2 in its boat-chair-boat conformation. The
most stable conformations for cyclooctane and cyclodecane
are boat-chair and boat-chair-boat, respectively. Clearly, the
host-guest chemistry with H2 enables realization of high
energy forms at room temperature.32
rings in the inclusion compounds of all H1-H4 are found to
vary in the range of 68.1-89.9°. We believe that this rota-
tional freedom confers the hosts H1-H4 with sufficient
flexibility to adopt structures complementary to those of
the guests. Further, the crystal packings in all of the inclusion
compounds of H1-H4 are governed by weak intermolecular
interactions such as C-H O hydrogen bonds and
3 3 3
C-H π interactions.22 As a result, change in the crystal
3 3 3
Generalizations about the Properties of Inclusion Hosts
H1-H4 and Their Adaptability. The inclusion behavior
observed with hosts H1-H4 amply suggests that their
skeletal features are robust to minor structural modifica-
tions. This is significant given that the crystal packings of
organic molecules in general change dramatically with subtle
structural modifications. It emerges from a comparative
study of the inclusion compounds of H1, H2, and H4 with
aliphatic as well as aromatic guest molecules in Table 1 that
the void volumes can be modulated. Although H4 is advan-
tageous as revealed by the data on guest-accessible volumes,
cf. Table 1, the entropically more labile methoxymethyl
groups in H4 might in some instances reduce the guest-
accessible volume. One is tempted to believe that the highly
symmetrical molecular systems with orthogonal aromatic
planes might lack conformational freedom to pack effi-
ciently in the solid state and that this inefficiency in close
packing should be the origin for the observed guest inclusion.
This indeed was our initial premise on the basis of which the
hosts H1-H4 were designed. However, this is entirely not
true; the host systems H2 and H4 that are largely explored for
guest inclusion also crystallize in their guest-free form. The
inclusion behavior of host H2 with almost any guest clearly
points to the fact that H2 and its analogues, i.e., H1, H3 and
H4, are highly adaptable. The adaptability appears to owe its
origin to two important factors, moderate conformational
flexibility and lattice energy conservation through weak
intermolecular interactions. For guest-induced adaptability
of the host systems, it is imperative that the hosts are able to
explore moderate conformational flexibility to include
guests efficiently. As mentioned earlier, the 2,6-dimethylaryl
rings that are orthogonal to the central pyrene rings are
indeed associated with moderate rotational freedom. The
angles between the central pyrene ring and the dimethylaryl
packing with a change in the guest structure may not lead to
dramatic variation in the crystal lattice stabilization energy.
This implies that hydrogen-bonded host systems are most
likely to be sensitive to changes in guest structures, unless the
structures of the hosts intrinsically contain several functional
groups capable of strong intermolecular interactions and
contribute to the overall lattice stabilization, e.g., choleic
acids15c and gossypol.15 The conformation and lattice energy
compensation put forward by Nangia and co-workers in the
context of polymorphism observed with 4,4-diphenyl-2,5-
cyclohexanedione is noteworthy in this context.27 The con-
formational changes to accommodate the guest molecules by
hosts H1-H4 appear to be compensated for by crystal lattice
stabilization.
The unique feature of the hosts H1-H4 is the binding of
aliphatic and aromatic guests differently. In general, the
small-sized guest molecules are found to be located in the
basin region, while aliphatic and aromatic guests are found
in the channels and troughs, respectively. This novel mode of
guest binding may pave the way for exploiting inclusion of
two or more guest molecules in a single component to access
multicomponent molecular crystals in a predictive manner.
Conclusions
On the basis of a rational design, we have developed
tetraarylpyrenes H1-H4 as a new class of inclusion host
systems that exhibit remarkable guest inclusion. In particu-
lar, H2 is found to include a broad range of guest molecules.
We have determined 42 crystal structures in all, of which 28
structures correspond to the inclusion compounds of H2
alone. The X-ray crystal structure analyses reveal favored
locations for the guests in that the small-sized guest mole-
cules such as dimethyl sulfide, chloroform, etc. are found to
occupy the basin regions of the host (Scheme 1), whereas
aliphatic guests are found to be included in concave/channel
regions and the aromatic guests in troughs. In essence, the
hosts are found to behave like molecular tweezers in includ-
ing a variety of guest molecules with a high degree of
(31) Hirano, S.; Toyota, S.; Toda, F. Chem. Commun. 2004, 2354.
(32) (a) Powar, D. M.; Smith, S. V.; Mark, H. L.; Odom, R. M.; Noe,
E. A. J. Am. Chem. Soc. 1998, 120, 10715. (b) Dorofeeva, O. V.; Mastryukov,
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8576 J. Org. Chem. Vol. 74, No. 22, 2009

Moorthy et al.
JOCArticle
adaptability. The crystal structure analyses also reveal a
varied yet limited number of modes in which the host
molecules are found to organize. Indeed, as many as 20 inclu-
sion compounds of H2 out of 28 are found to be isostructur-
al. The comprehensive structural investigations of a number
of inclusion compounds demonstrate how conformational
flexibility when combined with molecular attributes may be
elegantly exploited for remarkable host-guest phenomena.
We have exploited the shape-selective inclusion behavior
observed with H2 to demonstrate its utility in (i) the separa-
tion of the regio- and stereoisomeric mixtures, (ii) the
stabilization of one of the tautomeric forms of 1,3-diketone,
and (iii) the locking of conformationally flexible cycloalk-
anes in one/two of their conformations. In addition to
applications in chiral resolution and fluorescence-based
guest signaling, these novel inclusion host systems with
inherently different domains for guest inclusion are believed
to be attractive to predictively access multicomponent or-
ganic molecular crystals, which are a challenge. We are
continuing our investigations to exploit the unique structural
attributes of H1-H4 for development of functional organic
materials.
Subsequently, the heating was continued for additional 6 h,
after which time the reaction mixture turned dark brown. At this
stage, the reaction mixture was cooled and extracted with
CHCl3. The combined extracts were washed with brine, dried
over Na2SO4 , and concentrated. The pure tetraarylpyrene H4
was isolated by silica gel column chromatography using petro-
leum ether as an eluent. Yield 1.02 g (70%): mp 251-253 °C; 1H
NMR (400 MHz, CDCl3) δ 1.90 (s, 24H), 3.38 (s, 12H), 4.41 (s,
8H), 7.16 (s, 8H), 7.44 (s, 4H), 7.51 (s, 2H); 13C NMR (100 MHz,
CDCl3) δ 20.8, 58.2, 74.8, 124.8, 125.9, 126.8, 128.4, 128.6,
136.2, 137.1, 137.2, 139.4; ESI-MSþ m/z calcd for C56H58O4
795.442 [M þ H], found 795.4413.
Formation of Inclusion Compounds. In a typical experiment,
50 mg of host (H1-H4) and 15 mg of guest were taken in a
10-mL glass vial and dissolved in ca. 3-4 mL of chloroform.
Slow evaporation of the resulting solution over 2-3 days led to
crystals in a quantitative yield, which were carefully isolated.
For volatile liquid guests, the host (H1/H2/H3/H4) was directly
dissolved in the neat guest (2 mL). Slow evaporation of the
solution led to crystals of the inclusion compound in a quanti-
tative yield.
X-ray Crystal Structure Determinations. A good quality
crystal in each case was mounted in a glass capillary and cooled
to 100 K, and the intensity data were collected on a Bruker
Nonius SMART APEX CCD detector system with Mo-sealed
Siemens ceramic diffraction tube (λ = 0.71073) and a highly
oriented graphite monochromator operating at 50 kV and
30 mA. The data were collected on a hemisphere mode and
processed with SAINTPLUS. Empirical absorption correction
was made using SADABS. The structure was solved in each case
by Direct Methods using the SHELXTL package and refined
by full matrix least-squares method based on F2 using the
SHELX97 program.34 All non-hydrogen atoms were refined
anisotropically. The hydrogen atoms were included in the ideal
positions with fixed isotropic U values and were riding with their
respective non-hydrogen atoms. The experimental details of
crystal data, intensity measurements, structure solution, and
refinement are contained in Supporting Information.
Experimental Section
The general procedure for the synthesis of tetrarylpyrenes
H1-H4 involved four-fold Suzuki coupling of 1,3,6,8-tetrabromo-
pyrene with suitably functionalized boronic acids using Pd-
(PPh3)4 as a catalyst (Supporting Information); 1,3,6,8-tetra-
bromopyrene was synthesized by bromination of pyrene in
nitrobenzene.18c The preparation of hosts H1 and H2, i.e.,
1,3,6,8-tetrakis(2,4,6-trimethylphenyl)pyrene and 1,3,6,8-tetra-
kis(2,6-dimethyl-4-methoxyphenyl)pyrene, have previously been
published by us.18c 2,6-Dimethyl-4-isopropoxyphenylboro-
nic acid, required for H3, was synthesized according to a
literature procedure33 using 2,6-dimethyl-4-isopropoxybromo-
benzene as a starting material. 4-Methoxymethyl-2,6-di-
methylphenylboronic acid required for H4 was prepared
starting from bromomesitylene (Supporting Information).
The diarylbenzenes H5 and H6 were similarly prepared by
Suzuki coupling of 4,6-dibromo-m-xylene and 4,6-dibromo-
resorcinol dimethyl ether with appropriately functionalized
boronic acids under Pd(0)-catalyzed conditions (Supporting
Information). A representative procedure for the Suzuki
coupling is described below for the preparation of H4.
Acknowledgment. J.N.M. is thankful to DST (Depart-
ment of Science and Technology), India for funding under
Ramanna Research fellowship. P.N. is grateful to UGC for a
senior research fellowship. We thank the anonymous refer-
ees for insightful suggestions and comments.
A 100-mL two-necked round-bottom flask, removed hot
from an oven, was cooled under a N2 atmosphere and charged
with tetrabromopyrene (1.0 g, 1.93 mmol), 2,6-dimethyl-4-
methoxymethylphenylboronic acid (2.3 g, 11.6 mmol), Pd-
(PPh3)4 (0.25 g, 10 mol %), dioxane (40 mL), and 20% NaOH
solution (10 mL). The reaction mixture was heated at 90 °C.
The pale-green turbid solution turned clear yellow in 6 h.
Supporting Information Available: Details of synthesis,
spectroscopic characterization data, spectral reproductions,
crystal data for all compounds, TGA profiles, experimental
and simulated PXRD patterns, ORTEP drawings of the molec-
ular structures of all compounds, crystal packing diagrams,
and CIF files. This material is available free of charge via the
Internet at http://pubs.acs.org.
(33) Kang, H.; Facchetti, A.; stem, C. L.; Rheingold, A. R.; Kassel, W. S.;
Marks, T. J. Org. Lett. 2005, 7, 3721.
(34) Sheldrick, G. M. SHELX97 Program for the Refinement and Solution
of Crystal Structures; University of Gottingen: Gottingen, Germany, 1997.
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