A new host 2,3,6,7,10,11-hexahydroxy triphenylene which forms chiral inclusion crystalline lattice: X-ray structural study of the chiral crystalline lattice

Article abstract of DOI:10.1002/(SICI)1099-1395(200001)13:1<39::AID-POC203>3.0.CO;2-8

The title compound was found to form an inclusion complex crystal with various kinds of guests. It was also found that crystalline lattice of some inclusion complex is chiral. By an enantioselective inclusion complexation in the chiral lattice, the racemic guest was resolved. The chiral crystalline lattice was studied by X-ray analysis. Solid-state synthesis of the title host compound is also described. Copyright

Full text of DOI:10.1002/(SICI)1099-1395(200001)13:1<39::AID-POC203>3.0.CO;2-8

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2000: 13; 39–45
A new host 2,3,6,7,10,11-hexahydroxy triphenylene which
forms chiral inclusion crystalline lattice: X-ray structural
study of the chiral crystalline lattice
Fumio Toda,1* Koichi Tanaka,1 Takeshi Matsumoto,1 Tadashi Nakai,2 Ikuko Miyahara2 and Ken Hirotsu2
1Department of Applied Chemistry, Faculty of Engineering, Ehime University, Matsuyama, Ehime 790-8577, Japan
2Department of Chemistry, Graduate School of Science, Osaka City University, Sugimoto, Sumiyoshi-ku, Osaka 558-8585, Japan
Received 27 January 1999; revised 10 July 1999; accepted 15 July 1999
ABSTRACT: The title compound was found to form an inclusion complex crystal with various kinds of guests. It was
epoc
also found that crystalline lattice of some inclusion complex is chiral. By an enantioselective inclusion complexation
in the chiral lattice, the racemic guest was resolved. The chiral crystalline lattice was studied by X-ray analysis. Solid-
state synthesis of the title host compound is also described. Copyright 2000 John Wiley & Sons, Ltd.
KEYWORDS: inclusion crystal; chiral crystal; hexahydroxytriphenylene; optical resolution
Additional material for this paper is available from the epoc website at http://www.wiley.com/epoc
It is known that some achiral molecules are arranged in a
chiral form in their own crystals and their solid-state
reaction gives chiral products.1 In the case that achiral
molecules cannot arrange in a chiral form in their own
crystals, a chiral host molecule assists to arrange these
achiral molecules in a chiral form in their host–guest
inclusion complex crystal which upon solid-state reaction
gives chiral product.2 We have been looking for an
achiral host compound which arranges in a chiral form to
form a chiral inclusion crystalline lattice and have finally
found that the title achiral compound 2 forms chiral
crystalline lattice in which guest molecules are accom-
modated. X-ray analysis of a chiral 1:3 inclusion
compound of 2 with cyclopentanone showed that the
chirality is induced by the formation of chiral helix of 2
molecules through their hydrogen bond network.
Although the title compound 2 is important as a
material,3 its most reasonable synthetic method, trimer-
ization of catechol 1 in solution, is not effective. Heating
of a solution of 1 in the presence of FeCl3 gives 2 as a
brown crystal in 2% yield. This synthetic method is rather
complicated and gives colored impure 2 in low yield.
Although a convenient trimerization method of catechol
dialkyl ether in the presence of MoCl5 in CH2Cl2 to give
hexaalkyl ether of 2 has been reported,4 its conversion to
2 by an ether bond cleavage is very difficult. We report a
simple synthetic method in the solid state which gives
colorless 2 in relatively high yield. We also report that 2
shows inclusion ability for various kinds of guest
compounds, and that 2 forms achiral inclusion crystalline
lattice with some guest molecules. The chiral structure
was proven by measurement of CD spectra in Nujol mull
and X-ray crystal structure analysis for a 1:3 inclusion
complex of 2 with cyclopentanone.
Previously we have reported a simple but very
effective synthetic method of 2,2'-dihydroxy-1,1'-bi-
naphthyl by the solid-state coupling reaction of 2-
naphthol in the presence of FeCl3Á6H2O under ultrasonic
irradiation. We found this solid-state synthetic method is
applicable to the trimerization reaction of 1 to 2. A
mixture of powdered 1 and FeCl3Á6H2O was irradiated
with ultrasound (28 kHz) for 24 h, and the reaction
mixture was worked up to give 2 as brown crystals in
37% yield. The colored product contained quinoid
derivatives of 2 and was difficult to purify to get a
*Correspondence to: F. Toda, Department of Applied Chemistry,
Faculty of Engineering, Ehime University, Matsuyama, Ehime 790-
8577, Japan.
Copyright 2000 John Wiley & Sons, Ltd.
CCC 0894–3230/2000/010039–07 $17.50

40
F. TODA ET AL.
Table 1. Host±guest ratio of inclusion complexes of 2a
Guest
host/guestb
n-PrOH
1:3
1:2c
1:3
1:3
1:2
nc
i-PrOH
n-BuOH
Cyclopentanol
Cyclohexanol
Acetone
Acetonylacetone
Cyclopentanone
Cyclopentanone
Cyclopentenone
2-Methylcyclopentanone
3-Methylcyclopentanone
Cyclohexenone
Cyclohexanone
2-Methylcyclohexanone
3-Methylcyclohexanone
g-Butyrolactone
THF
2:3
1:3c
1:4:H2O
1:3c
1:3c
1:3
1:3c
1:3
1:3
1:3
1:3
1:2
1:2
1:2
1,4-dioxane
DMF
a
All melting points are unclear.
Figure 2. CD spectra of two enantiomeric 1:3 inclusion
crystals of 2 with 2-cyclopentenone in Nujol mulls
b The ratio was determined by H-NMR or TG measurement.
1
c
Chiral inclusion compound.
When 2 is recrystallized from usual solvents, inclusion
crystals are formed, containing the solvent molecules in
host-guest ratios as indicated in Table 1. Of these
inclusion crystals, those with achiral guests, such as i-
PrOH, cyclopentanone, 2-cyclopentenone and 2-cyclo-
hexenone, are found to be chiral by measurement of the
CD spectra in Nujol mulls.5 In each case, one piece of the
inclusion crystal showed (‡)-Cotton effect and the other
piece of crystal showed ( )-Cotton effect, and these two
colorless sample by usual methods such as recrystalliza-
tion from the solvent. Purification of 2 by inclusion
complexation with a guest compound was developed. For
example, recrystallizations of 2 from cyclopentanone 3
gave a 2Ácyclopentanone 1:3 inclusion complex 4 as
colorless prisms. Evaporation of the cyclopentanone
guest molecules from 4 gave pure 2 as colorless crystals
in 16% yield (m.p. 387°C).
Figure 1. CD spectra of two enantiomeric 1:3 inclusion
crystals of 2 with cyclopentanone in Nujol mulls
Figure 3. CD spectra of two enantiomeric 1:3 inclusion
crystals of 2 with 2-cyclohexenone in Nujol mulls
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2,3,6,7,10,11-HEXAHYDROXYTRIPHENYLENE
41
showed nicely mirror imaged spectra, as shown in Figs 1–
4. It has been well established that chirality in the
crystalline state can easily be detected by measurement of
CD spectra in Nujol mulls. In order to clarify the reason
why achiral host molecules of 2 form chiral crystalline
lattice with achiral guest molecules, the X-ray crystal
structure of 4 was studied. Interestingly, however,
inclusion complex 5 of 2 with cyclopentanone and H2O
in 1:4:1 is achiral. The X-ray crystal structure of 5 was
also studied.
Figure 5 illustrates the conformation of 4 with the
hydrogen bonding interactions between compound 2
and cyclopentanone. The hydroxyl groups, O3-H, O9-H
and O15-H, make intramolecular hydrogen bonds as
donors with O4, O10 and O16, respectively. The
carbonyl oxygens of cyclopentanones, O21, O31 and
O41, act as acceptors in hydrogen bonds from O3-H, O4-
H and O9-H, respectively. Thus, O3-H and O9-H are
involved in bifurcated hydrogen bonds as shown in
Fig. 5. The compound 2 in 4 is roughly flat [within 0.14
˚
(1) A]. However, the molecule is distorted from the
Figure 4. CD spectra of two enantiomeric 1:3 inclusion
crystals of 2 with 2-methylcyclopentanone in Nujol mulls
planarity because of the steric repulsion between
Figure 5. Perspective plot of complex (4) showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50%
probability level except for hydrogen atoms
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42
F. TODA ET AL.
Figure 6. Molecular packing and hydrogen bonding of complex (4) viewed down the a-axis. The hydrogen bonds are shown by
thin lines
hydrogens on carbon atoms at peri-positions. The
rings B and C are bent down and up from the central
ring A, and the ring D is twisted against the ring A
with the dihedral angles of C5–C6–C7–C8 = 2.8(6)°,
C11–C12–C13–C14 = 2.2(6)°, and C2–C1–C18–C17 =
2.4(5)°. The three joint bonds which link the catechol
molecules and the central benzene ring are lengthened by
respectively. The water molecule (O1) acts as an acceptor
and a donor to bridge O9-H and O41. The compound 2 in
5 shows slightly larger distortion than that observed in 4
˚
with the maximum deviation of 0.267 A from the mean
plane. The rings B' and D' are bent up and down from the
central ring A', and the ring C' is twisted against the ring
A with the dihedral angles of C5–C6–C7–C8 = 7.6(5)°,
C11–C12–C13–C14 = 3.2(4)°, and C2–C1–C18–C17 =
5.1(5)°. The three joint bonds between the catechol
moieties and the central benzene ring are lengthened by
˚
about 0.064 A compared with the other bonds of the ring
A in order to reduce the steric repulsion between the
hydrogen atoms: C6–C7 = 1.469(5), C12–C13 =
1.477(5), C1–C18 = 1.469(5), C1–C6 = 1.406(5), C7–
˚
about 0.055 A compared with the other three bonds of the
˚
C12 = 1.411(6) and C13–C18 = 1.407(5) A. The molecu-
ring A in order to reduce the steric repulsion between
hydrogens on carbon atoms at peri-positions: C6–C7 =
1.465(4), C12–C13 = 1.464(4), C1–C18 =1.466(4), C1–
C6 = 1.412(4), C7–C12 = 1.404(6) and C13–C18 =
lar packing and the hydrogen bonding scheme of 4 are
shown in Fig. 6. There are two major hydrogen bond
sequences. One comprises an infinite chain: ---O9-H---
O10-H---O9-H--- with an additional O9-H---O41. The
other system consists of a five-link finite chain: O15-H---
O16-H---O3H---O4-H---O31 with an additional O3-H---
O21. The intermolecular hydrogen bonds, O10-H---O9
and O16-H---O3, link the host molecules (2) around the
21 screw axes passing through x = 0 and z = 1/2, and
x = 1/2 and z = 0 (or 1), respectively, indicating that the
molecules 2 are connected by two-dimensional hydrogen
bond networks. These networks are parallel to the (1
˚
1.413(4) A.
The molecular packing and the hydrogen bonding
scheme of 5 is shown in Fig. 8. There are two major
hydrogen bond sequences. One comprises a finite chain:
O10-H---O3-H---O4-H---O31 with a branched hydrogen
bond, O3-H---O21. The other system consists of a five-
link cyclic system: O15-H---O9-H---O1-H---O51---H-
O16---H-O15 with a branch, O3-H---O21. The hydroxyl
groups, O3-H and O15-H are included in the bifurcated
hydrogen bonds. The O9-H was judged not to be included
in the intramolecular hydrogen bond with O10 because of
0
1) plane and cyclopentanone molecules occupy the
space between these networks.
˚
Figure 7 illustrates the conformation of 5 with the
hydrogen bonding interactions between the compound 2,
and four cyclopentanones and a water molecule. The
hydroxyl groups, O3-H, O9-H and O15-H, make intra-
molecular hydrogen bonds as donors with O4, O10 and
O16, similarly to those shown in Fig. 5. The O3-H, O4-H
and O16-H act as hydrogen bonding donors to interact
with the carbonyl oxygens, O21, O31 and O51,
the long O---H distance [2.47(4) A] and the large
deviation from the linearity of O-H---O [102(4)°],
although there should be a weak interaction between
O9-H and O10.
The intermolecular hydrogen bond, O15-H---O9, links
the host molecules (2) along the b-axis, to form a chiral
arrangement of 2 along the 21 screw axes. This helical
arrangement of 2 is connected to the other helical one of
Copyright 2000 John Wiley & Sons, Ltd.
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2,3,6,7,10,11-HEXAHYDROXYTRIPHENYLENE
43
Figure 7. Perspective plot of complex (5) showing the atom-numbering scheme. Displacement ellipsoids are drawn at the 50%
probability level except for hydrogen atoms
the opposite chirality through the hydrogen bond, O10-
H---O3, to give an achiral hydrogen bond networks in
two-dimension. These networks are parallel to the bc
plane and cyclopentanone molecules occupy the space
between these networks similarly to that found in
complex 4.
chirality. In the inclusion complex of 4, the two-
dimensional networks of same chirality stack with a
larger van der Waal stabilization than those of opposite
chirality.
We cannot see the reason why the inclusion complex
between the molecules 2 and cyclopentanones gives the
optically resolved crystal (4) on the one hand and the
achiral crystal (5) on the other. However, there are some
interesting features in these crystals. The predominant
factor to determine the molecular arrangements is
extensive hydrogen bonds in the crystal. The hosts (2)
and guests (cyclopentanone and water in 5) which are
hydrogen bonded in a two-dimensional way, roughly
arrange in one plane. In the crystal 4, the molecules on
the plane are related only by 21 screw axes, indicating
that this plane is chiral, while in the crystal 5, the
molecules are related by 21 screw axes and center of
symmetries, resulting in the achiral plane. The planes just
stack one by one to make a chiral crystal in 4 and an
achiral crystal in 5.
In solution, the host molecules might make three
intramolecular hydrogen bonds for entropy reasons and
interact with as many guests (cyclopentanone) as possible
to make transient complexes like that shown in Figs 5 and
7. When the concentration of the solution goes up, the
host molecules can interact with other hosts by using the
free O-H groups formed by releasing cyclopentanones to
expand the hydrogen bond network. The network will be
reasonably planar since the molecule 2 and cyclopenta-
none are approximately planar. The right-handed and
left-handed short helices are formed at equal weight. It
seems that the alternative arrangements of right- and left-
handed helixes are energetically favorable in 5, while
there are two ways: one is stacking of the networks with
the same chirality to form a chiral crystal, and the other is
the alternative stacking of the networks with the opposite
When a racemic guest compound is accommodated
enantioselectively in the chiral crystalline lattice formed
Copyright 2000 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2000: 13; 39–45

44
F. TODA ET AL.
Figure 8. Molecular packing and hydrogen bonding of complex (5) viewed down the a-axis. The hydrogen bonds are shown by
thin lines
1
by the chiral arrangement of the achiral host 2, optical
resolution without using any chiral source becomes
possible. Recrystallization of 2 from 2-methylcyclopen-
tanone 6 gave their 1:3 inclusion crystals. One piece of
the crystal showed (‡)-Cotton effect at around 300 nm in
the solid state CD spectrum, and the other piece of crystal
showed ( )-Cotton effect at the same region (Fig. 4).
Heating of the former and latter crystals in vacuo gave
(‡)-6 of 34% ee and ( )-6 of 37% ee, respectively by
distillation. It is clear that chiral recognition of 6 occurs
in the chiral crystalline lattice formed by a chiral
arrangement of the achiral 2 molecules. However, in the
inclusion crystalline lattice of 2 with 2- and 3-methylcy-
clohexanone, the 2 molecules are not arranged in chiral
form and these racemic guests are not resolved (Table 1).
compound. vOH:2485 and 3425 cm
;
1H NMR
(CDCl3): ꢀ 7.7 (s, OH, 6H) and 8.7 (s, Ar, 6H). Found:
C, 66.67; H, 3.54%. Calculated for C18H12O6: C, 66.67%,
H, 3.73%.
Preparation of inclusion complexes of 2 with
guest compounds
Inclusion complex was prepared by recrystallization of 2
from the guest compound. For example, recrystallization
of 2 from cyclopentanone gave a 1:3 complex of 2 with
the guest as colorless prisms in a quantitative yield.
vOH:3270 cm 1, vC
=
O 1620 cm 1; 1H NMR: ꢀ 2.0 (m,
CH2, 12H), 2.2 (m, CH2, 12H), 7.7 (s, OH, 6H) and 8.7 (s,
Ar. 6H). Found: C, 68.75; H, 6.34%. Calculated for
C33H36O9: C, 68.74%, H, 6.29%. By the same procedure,
inclusion complexes indicated in Table 1 were prepared.
All complexes did not show a clear melting point. The
host:guest ratio was determined by 1H NMR or TG
measurement. By measurement of CD spectra of the
inclusion crystals in Nujol mulls, it was determined
whether the inclusion crystal is chiral or not. These data
are shown in Table 1.
EXPERIMENTAL
Synthesis of 2,3,6,7,10,11-hexahydroxytripheny-
lene (2) in the solid state
A mixture of finely powdered catecol (1 20 g, 0.182 mol)
and FeCl36H2O (196.8 g, 0.728 mol) was irradiated by
ultrasound for 24 h. The reaction mixture was washed
with dilute HCl and water, and the dried product was
extracted with hot cyclopentanone to give crude 2 (10 g,
51% yield). Recrystallization of the crude 2 from
cyclopentanone gave a 1:1 inclusion complex of 2 with
cyclopentanone (7.2 g) from which pure 2 (m.p. 387°C,
4 g, 20% yield) was obtained by evaporation of the guest
Optical resolution of 2-methylcyclopentanone by
inclusion complexation with 2
Recrystallization of 2 from 2-methylcyclopentanone (6)
gave their 1:3 inclusion complex crystals (7). Heating of
Copyright 2000 John Wiley & Sons, Ltd.
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2,3,6,7,10,11-HEXAHYDROXYTRIPHENYLENE
45
one piece of the crystal which shows a (‡)-Cotton effect
in the region of 300 nm in vacuo gave (‡)-6 of 34% ee
[a]D ‡ 17.2° (c 0.06, MeOH) by distillation. Heating of
the other piece of crystal which shows a ( )-Cotton
effect in the region of 300 nm in vacuo gave ( )-6 of
37% ee [a]D 18.5° (c 0.07, MeOH).
GOF = 2.08, maximum residual electron density 0.33 e
3
˚
A
.
Crystal data for 5: C18H12O6Á4C5H8OÁH2O, mono-
clinic, space group P21/c, MoKa radiation, a = 7.603(7),
˚
b = 20.937(3), c = 22.245(3) A, b = 91.85(3)°, V =
3
3539(3) A , Dc = 1.274 g cm 3, m = 0.93 cm 1, 2ꢁ max
˚
= 50°, 6423 independent intensities, 3930 observed [l
> 1.00s (l)], T = 296 K, weighting scheme = 1/[s2 (Fo)2
Crystallographic studies
‡ (0.03)2 Fo2] 1, R = 0.071, Rw = 0.082, GOF = 1.74,
3
˚
maximum residual electron density 0.19 e A
.
The X-ray data were collected on a Rigaku AFC7R four-
circle diffractometer, using !/2ꢁ scan mode. All calcula-
tions were performed with the crystallographic software
package teXsan (Molecular Structure Corporation, 1985,
1992). The structure was solved by direct methods6 and
subsequent Fourier recycling,7 and refined by full-matrix
least-squares refinement against jFj, with all hydrogen
atoms fixed at the calculated positions except hydroxy
hydrogens for 4. No absorption corrections were applied.
Full X-ray data for compounds 4 and 5 are available from
the epoc website at http://www.wiley.com/epoc/
REFERENCES
1. F. Toda, H. Miyamoto, H. Koshima and Z. Urbanczyk-Lipkowska,
J. Org. Chem., 62, 9261 (1997).
2. F. Toda, Synlett, 303 (1993); F. Toda, Acc. Chem. Res., 28, 480
(1995).
3. S. Chandrasekhar, Liq. Cryst., 14, 3 (1993).
4. S. Kumar and M. Manickam, J. Chem. Soc., Chem. Commun., 1615
(1997).
5. F. Toda, H. Miyamoto, S. Kikuchi, R. Kuroda and F. Nagami, J. Am.
Chem. Soc., 118, 11315 (1996); F. Toda, H. Miyamoto and K.
Knemoto, J. Am. Chem. Soc., 61, 6490 (1996).
6. G. M. Sheldrick Crystallographic Computing 3 (Eds G. M.
Sheldrick C. Kruger Goddard) Oxford University Press, Oxford,
175 (1985).
7. P. T. Beurskens, G. Admiraal, G. Beurskens, W. P. Bosman, R. de
Gelder, R. Israel, J. M. M. Smits, The DIRDIF-94 program system,
Technical Report of the Crystallography Laboratory, University of
Nijmegen, The Netherlands, 1994.
Crystal data for 4: C18H12O6Á3C5H8O, monoclinic,
space group P21, MoKa radiation, 2ꢁmax = 50°,
˚
a = 7.986(3), b = 10.161(2), c = 18.554(2) A, b =
99.84(1)°, V = 1483.5(5) A 3. Dc = 1.291 g cm 3, m
˚
= 0.94 cm 1, 2708 independent intensities, 2175 ob-
served [l > 1.00s (l)], T = 296 K, weighting scheme =
1/[s2 (Fo)2 ‡ (0.025)2 Fo2] 1, R = 0.058, Rw = 0.075,
Copyright 2000 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2000: 13; 39–45