Generation of chirality in a two-component molecular crystal of acridine and diphenylacetic acid and its absolute asymmetric photodecarboxylating condensation

Article abstract of DOI:10.1021/ja961106q

Despite the fact that acridine (1) and diphenylacetic acid (a) are achiral compounds, a chiral two-component molecular crystal (1·a) in which two molecules are self-assembled in a 1:1 molar ratio by hydrogen bonding crystallizes spontaneously from an acet

Full text of DOI:10.1021/ja961106q

J. Am. Chem. Soc. 1996, 118, 12059-12065
12059
Generation of Chirality in a Two-Component Molecular Crystal
of Acridine and Diphenylacetic Acid and Its Absolute
Asymmetric Photodecarboxylating Condensation
Hideko Koshima,*,†,‡ Kuiling Ding,† Yosuke Chisaka,† and Teruo Matsuura†
Contribution from the Department of Materials Chemistry, Faculty of Science and Technology,
Ryukoku UniVersity, Seta, Otsu 520-21, Japan, and PRESTO, Research DeVelopment Corporation
of Japan, Faculty of Science and Technology, Ryukoku UniVersity, Seta, Otsu 520-21, Japan
ReceiVed April 3, 1996X
Abstract: Despite the fact that acridine (1) and diphenylacetic acid (a) are achiral compounds, a chiral two-component
molecular crystal (1‚a) in which two molecules are self-assembled in a 1:1 molar ratio by hydrogen bonding crystallizes
spontaneously from an acetonitrile solution. The space group is P212121, which is typical chiral space group. Both
handed crystals (-)-1‚a and (+)-1‚a can be prepared as desired on a large scale by seeding. The two phenyl planes
and the carboxyl plane of the diphenylacetic acid molecule in the crystal (-)-1‚a have torsions in the same direction
as the blades of a propeller. The oppositely handed crystal (+)-1‚a has minus torsion angles. Irradiation of (-)-1‚a
or (+)-1‚a caused stereospecific decarboxylating condensation to give an excess of the chiral compound {(-)-3} or
{(+)-3} in about 35% ee, respectively, as the main product. The absolute configurations of the reactant (-)-1‚a and
the product (-)-3 could be determined to be (M)-(-)-1‚a and (S)-(-)-3 by the Bijvoet method based on anomalous
dispersion of an oxygen atom of (-)-1‚a and a sulfur atom of the trifluoromethanesulfonate salt of methylated (-)-3
during X-ray crystallographic analysis. Upon irradiating (M)-(-)-1‚a, the diphenylmethyl radical and the hydroacridine
radical are produced via electron transfer from a to 1 and subsequent proton transfer followed by decarboxylation.
The next radical coupling occurs with the shortest distance of 5.1 Å between the two preradical carbon atoms in the
crystal lattice to afford (S)-(-)-3 as the major enantiomer. On the other hand (R)-(+)-3 can be produced as the
minor enantiomer by coupling over a longer distance of 6.8 Å, resulting in a ca. 2:1 of S:R ratio, i.e., about 35% ee.
The radical coupling is necessarily accompanied by a slight movement of the radical species in the crystal lattice, in
contrast to the well-known topochemical [2+2] photocycloaddition.
Introduction
molecular crystals,5-9 we found that a chiral two-component
molecular crystal (1‚a) spontaneously crystallizes from a
solution of acridine (1) and diphenylacetic acid (a) in acetoni-
trile. Further we succeeded in carrying out an absolute
asymmetric synthesis by the solid-state photoreaction of chiral
1‚a.
Thus, chiral crystals composed of optically inactive molecules
can be useful as the reactants for absolute asymmetric syntheses,
because the chiral environment in the crystal lattice can cause
a stereospecific reaction due to the low mobility of molecules
in the crystalline state. In fact, since the first successful absolute
asymmetric [2+2] photocycloaddition in the solid state by
Elgavi et al.,10 more than 10 absolute asymmetric photochemical
syntheses have been achieved.11 However, most of these were
unimolecular (intramolecular) reactions caused in one-compo-
nent crystals such as the di-π-methane photorearrangement of
dibenzobarrelenes and the Norrish type II photorearrangement
by Scheffer et al.,12-15 the Norrish type II photocyclization of
Optically active molecules necessarily form chiral crystals.1
However, even if a molecule is not chiral, a chiral conformation
such as may be caused by molecular torsion, can induce
crystallization into a chiral crystal structure. For instance, a
crystal of benzophenone is chiral (space group P212121) by virtue
of the propeller-like arrangement of the phenyl rings.2 Such
crystals can be distinguished by knowing whether the space
group is chiral or not. A large number of chiral one-component
crystals that are composed of achiral organic compounds are
already known and compiled in the JCPDS crystal data series
and the Cambridge Crystallographic Data Centre. Statistically,
the most frequent chiral space groups are P212121 and P21 of
65 chiral space groups, which are included in 230 possible space
groups. However, chiral “two-component molecular crystals”3
composed of two achiral compounds are scarcely known until
now except for certain types of charge-transfer complexes.4 In
the course of our study of the photochemistry of two-component
(5) Koshima, H.; Matsuura, T. Kokagaku 1995, 19, 10-20.
(6) Koshima, H.; Chisaka, Y.; Wang, Y.; Yao, X.; Wang, H.; Wang, R.;
Maeda, A.; Matsuura, T. Tetrahedron 1994, 48, 13617-13630.
(7) Koshima, H.; Ding, K.; Matsuura, T. J. Chem. Soc., Chem. Commun.
1994, 2053-2054.
† Ryukoku University.
‡ PRESTO, Research Development Corp. of Japan.
X Abstract published in AdVance ACS Abstracts, November 1, 1996.
(1) Desiraju, G. R. Crystal Engineering: The Design of Organic Solids;
Elsevier: Amsterdam, 1989; pp 225-259.
(8) Koshima, H.; Ding, K.; Chisaka, Y.; Matsuura, T. Tetrahedron
Asymmetry 1995, 6, 101-104.
(2) Fleischer, E. B.; Sung, N.; Hawkinson, S. J. Phys. Chem. 1968, 72,
4311-4312.
(3) The term “two-component molecular crystal” used in this paper
defines a crystal in which two different organic compounds form a molecular
compound through intermolecular forces.
(9) Koshima, H.; Ding, K.; Chisaka, Y.; Matsuura, T.; Ohashi, Y.;
Mukasa, M. J. Org. Chem. 1996, 61, 2352-2357.
(10) Elgavi, J. A.; Green, B. S.; Schmidt, G. M. J. J. Am. Chem. Soc.
1973, 95, 2058-2059.
(4) For example: (a) Herbstein, F. H.; Kaftory, M. Acta Crystallogr.
1975, B31, 60-67. (b) Thozet, A.; Gaultier, J. Acta Crystallogr. 1977,
B33, 1052-1057. (c) Shaanan, B.; Shmueli, U. Acta Crystallogr. 1980,
B36, 2076-2082.
(11) Scheffer, J. R.; Garcia-Garibay, M. Photochemistry in Solid Surfaces;
Anpo, M., Matsuura, T., Eds.; Elsevier: Amsterdam, 1989; pp 501-525.
(12) Evans, S. V.; Garcia-Garibay, M.; Omkaram, N.; Scheffer, J. R.;
Trotter, J.; Wireko, F. J. Am. Chem. Soc. 1986, 108, 5648-5650.
S0002-7863(96)01106-7 CCC: $12.00 © 1996 American Chemical Society

12060 J. Am. Chem. Soc., Vol. 118, No. 48, 1996
Koshima et al.
oxoamides to â-lactams by Toda et al.,16-18 and the [2+2]
photocyclization of imides and thioamides by Sakamoto et
al.19,20 Bimolecular (intermolecular) examples are limited to
[2+2] photocycloadditions in one-component crystals21,22 and
two-component molecular crystals.10 Recent excellent work by
Suzuki et al. also involves the [2+2] photocycloaddition of a
chiral crystalline charge-transfer complex of bis[1,2,5]thia-
diazolotetracyanoquinodimethane and o-divinylbenzene via a
single crystal-to-single crystal transformation.23
Scheme 1
Unimolecular reactions for solid-state asymmetric synthesis
have the advantage of not requiring specific crystal packing
arrangements. However, as our study showed,5 bimolecular
reactions of two-component molecular crystals can in principle
lead to a greater variety of reaction types such as addition6 and
decarboxylation7-9 than in the case of unimolecular reac-
tions.11,24,25 For example, even if a simple compound is not
photosensitive, the formation of a two-component molecular
crystal in which a second component is combined as a sensitizer
can induce photoreactivity by electron-transfer sensitization.7
We report in this paper that crystal chirality is generated in a
two-component molecular crystal 1‚a and that an absolute
asymmetric synthesis can be achieved by a solid-state photo-
decarboxylating condensation. In addition, the reaction stereo-
chemistry could be mapped out by determining the absolute
configurations of the reactant and product and correlating them
with a given crystal reaction.
irradiated with a xenon lamp through a UV transparent filter
under argon for 1 h at -30 °C. The photoproduct consisted of
an excess of (-)-3 in 33% ee by HPLC analysis with a chiral
column. The second piece was submitted to X-ray crystal-
lographic analysis. The crystal is orthorhombic and belongs to
the chiral space group P212121 (Table 1). The absolute
configuration could be determined with a fairly high degree of
certainty by the Bijvoet method based on anomalous dispersion
of the oxygen atom with Cu KR radiation.26 The details are
described in the Experimental Section. Figure 1 shows the
molecular packing in (-)-1‚a for the correct absolute config-
uration. The molecular pair of 1 and a is connected through
O-H‚‚‚N hydrogen bonding with an H‚‚‚N distance of 1.92 Å
and an O-H‚‚‚N angle of 148° (Figure 2A). The angle between
the acridine plane and the carboxyl plane of the molecular pair
is 35.5°. The two phenyl planes and the carboxyl plane of the
diphenylacetic acid molecule in the crystal (-)-1‚a have torsions
in the same direction as the blades of a propeller. The three
torsion angles of (-)-1‚a are positive as listed in Table 2. All
four molecular pairs present in the unit cell have the same
absolute configuration (Figure 1). If the diphenylacetic acid
molecule is compared to three blades of a propeller, a helix
generates around the H1-C1 bond in a counterclockwise
direction. That is, the helicity around H1-C1 bond is minus
(Figure 2A).27 Therefore the crystal (-)-1‚a should be desig-
nated as (M)-(-)-1‚a. The oppositely handed crystal (+)-1‚a
has minus torsion angles (Table 2) and the helicity is plus
(Figure 2B). The molecular pairs (M)-(-)-1‚a and (P)-(+)-
1‚a have a mirror image relationship (Figure 2A,B).
Results and Discussion
Generation of Chirality. A 1:1 chiral two-component
molecular crystal 1‚a of acridine 1 and diphenylacetic acid a
could be prepared by slow evaporation of an equimolar solution
of 1 and a in acetonitrile at room temperature (Scheme 1). The
crystal exists as light-yellow rods, and the melting point is 101
°C, which is lower than the melting points of the components
1 (107 °C) and a (148 °C). There exist both enantiomorphous
crystals (-)-1‚a and (+)-1‚a. The single crystals that gave
enantiomeric excesses of (-)-3 and (+)-3 were named (-)-1‚a
and (+)-1‚a, respectively. By seeding we could easily obtain
crystals with the same chirality as the seed crystal.
A single crystal of (-)-1‚a (ca 3 mg), prepared by seeding,
was cut into two pieces. One piece was pulverized and
On the other hand, the crystal (a) of diphenylacetic acid alone
is achiral (Table 1, space group P21/n). Because the antipodal
molecules of diphenylacetic acid form a dimer through the
hydrogen bonding O-H‚‚‚O with the distance H‚‚‚O of 1.73
Å (Figure 2C), the positive and negative torsion angles exist
together in the dimer (Table 2). Therefore, the chiralities of
the two molecules in the crystal a is compensated and does not
appear. Preparation of the chiral crystal 1‚a from an equimolar
solution of 1 and a by seeding followed by evaporating the
solvent completely resulted in the crystals with the same absolute
configuration as the seed crystal in a nearly quantitative yield.
This was deduced from the ee values (35-39%) of the
photoproduct (3) obtained from the whole pulverized crystals
in the vessel, which were consistent with those from the single
crystals in Table 3. This indicates that the phenyl and carboxyl
groups of molecule a are sufficiently mobile in solution to allow
M to P inversion, despite the fact that such motions are difficult
to accomplish with space filling molecular models.
(13) Garcia-Garibay, M.; Scheffer, J. R.; Trotter, J.; Wireko, F. J. Am.
Chem. Soc. 1989, 111, 4985-4986.
(14) Chen, J.; Pokkuluri, P. R.; Scheffer, J. R.; Trotter, J. Tetrahedron
Lett. 1990, 31, 6803-6806.
(15) Fu, T. Y.; Liu, Z.; Scheffer, J. R.; Trotter, J. J. Am. Chem. Soc.
1993, 115, 12202-12203.
(16) Toda, F.; Yagi, M.; Soda, S. J. Chem. Soc., Chem. Commun. 1987,
1413-1414.
(17) Sekine, A.; Hori, K.; Ohashi, Y.; Yagi, M.; Toda, F. J. Am. Chem.
Soc. 1989, 111, 697-699.
(18) Toda, F.; Miyamoto, H. J. Chem. Soc., Perkin Trans. 1 1993, 1129-
1132.
(19) Sakamoto, M.; Takahashi, M.; Fujita, T.; Watanabe, S.; Iida, I.;
Nishio, T.; Aoyama, H. J. Org. Chem. 1993, 58, 3476-3477.
(20) Sakamoto, M.; Hokari, N.; Takahashi, M.; Fujita, T.; Watanabe,
S.; Iida, I.; Nishio, T. J. Am. Chem. Soc. 1993, 115, 818.
(21) (a) Addadi, L.; Cohen, M. D.; Lahav, M. J. Chem. Soc., Chem.
Commun. 1975, 471-473. (b) Addadi, L.; Lahav, M. J. Am. Chem. Soc.
1979, 101, 2152. (c) van Mil, J.; Addadi, L.; Gati, E.; Lahav, M. J. Am.
Chem. Soc. 1982, 104, 3429. (d) Addadi, L.; van Mil, J.; Lahav, M. J.
Am. Chem. Soc. 1982, 104, 3422-3429.
(22) Hasegawa, M.; Chung, C.-M.; Muro, N.; Maekawa, Y. J. Am. Chem.
Soc. 1990, 112, 5676-5677.
We tried to find additional chiral two-component molecular
crystals based on similar propeller-shaped molecules. 2,2-
(23) Suzuki, T.; Fukushima, T.; Yamashita, Y.; Miyashi, T. J. Am. Chem.
Soc. 1994, 116, 2793-2803.
(24) Scheffer, J. R.; Theocharis, C. R.; Jones, W.; Kearsley, S. K.; Pradad,
P. N.; Hasegawa, M. Organic Solid State Chemistry; Desiraju, G. R., Ed.;
Elsevier: Amsterdam, 1987; pp 1-177.
(26) Le page, Y.; Gabe, E. J.; Gainsford, G. J. Appl. Crystallogr. 1990,
23, 406-411.
(25) Saigo, K.; Hasegawa, M. ReactiVity in Molecular Crystals; Ohashi,
Y., Ed.; VCH: Weinheim, 1993; pp 203-235.
(27) Cahn, R. S.; Ingold, C.; Prelog, V. Angew. Chem. 1966, 78, 413-
447.

Generation of Chirality in a Two-Molecule Crystal
J. Am. Chem. Soc., Vol. 118, No. 48, 1996 12061
Table 1. X-ray Crystallographic Data for Molecular Crystals and Products
a
(-)-1‚a
{(-)-3}2‚MeOH
(-)-7
1‚b
formula
fw
space group
Z
C14H12O2
212.25
P21/n
4
C27H21NO2
391.47
P212121
4
C53H46N2O
726.96
P1
1
C28H24NO3SF3
C28H23NO2
405.50
P21/n
511.56
P21
4
4
cell constants
a, Å
b, Å
12.254(4)
7.226(3)
12.737(2)
90.00
90.99(2)
90.00
1127.6(6)
1.250
0.83
Mo KR
50.0
ω-2θ
2273
2168
14.908(4)
25.367(6)
5.457(3)
90.00
90.00
90.00
2063(1)
1.260
6.25
Cu KR
110.0
ω-2θ
10378
1570
9.871(1)
17.6408(9)
6.1787(9)
90.280(7)
107.31(1)
101.002(6)
1006.1(2)
1.200
0.70
Mo KR
50.0
ω-2θ
3771
3548
3161
687
13.363(5)
10.277(4)
18.792(4)
90.00
107.42(2)
90.00
2462(1)
1.380
16.38
Cu KR
120.0
ω-2θ
10456
3901
12.717(6)
13.061(9)
13.542(5)
90.00
105.57(3)
90.00
2166(2)
1.243
0.78
Mo KR
50.0
ω-2θ
4187
4000
c, Å
R, deg
â, deg
γ, deg
V, Å3
D
calcd, g cm-3
µ, cm-1
radiation
2θmax, deg
scan mode
no. of reflns measd
no. of unique reflns
no. of I > 3.00σ(I)
no. of variables
R, %
1418
149
3.6
1501
275
4.3
3445
673
6.5
1852
290
5.2
3.3
Rw, %
5.7
5.8
5.0
10.2
6.7
Figure 1. Molecular packing in the unit cell of the chiral crystal (-)-
1‚a of acridine (1) and diphenylacetic acid (a).
Diphenylpropionic acid (b), which is a methyl-substituted
derivative of a, was selected (Scheme 1). A two-component
molecular crystal (1‚b) could be prepared by slow evaporation
of an equimolar solution of 1 and b in ethanol. The 1:1 crystal
is yellow and the melting point is 139 °C, which is between
that of 1 (107 °C) and b (178 °C). However, the crystal was
not chiral (achiral space group P21/n) as shown in Table 1. The
molecular arrangement in the unit cell has a center of symmetry
as illustrated in Figure 3. The molecular pair of 1 and b is
connected through O-H‚‚‚N hydrogen bonding with an H‚‚‚N
Figure 2. Molecular pairs in the crystals: A, (-)-1‚a; B, (+)-1‚a; C,
a alone; D, 1‚b.
distance of 1.83 Å and an O-H‚‚‚N angle of 157° (Figure 2D).
Enantiomeric molecular pairs with plus and minus torsion angles
in b compensate the chirality in the crystal 1‚b (Table 2).
Why does 1‚b not share the same chiral crystallization of
1‚a? Figure 4 shows the stacking arrangements of two
molecular pairs in the crystals (-)-1‚a and 1‚b. The molecular
pairs of 1 and a in the crystal (-)-1‚a (A) stack in a head-to-

12062 J. Am. Chem. Soc., Vol. 118, No. 48, 1996
Koshima et al.
Table 2. Torsion Angles in the Crystals
torsion angle (deg)
(-)-1‚a
H1-C1-C2-C3
H1-C1-C4-C5
H1-C1-C6-O1
13.0
50.3
33.9
(+)-1‚a
H1′-C1′-C2′-C3′
H1′-C1′-C4′-C5′
H1′-C1′-C6′-O1′
-13.0
-50.3
-33.9
a
H3-C7-C8-C9
H3-C7-C10-C11
H3-C7-C12-O3
H3′-C7′-C8′-C9′
H3′-C7′-C12′-C11′
H3′-C7′-C12′-O3′
52.8
27.3
48.2
-52.8
-27.3
-48.2
1‚b
C13-C14-C15-C16
C13-C14-C17-C18
C13-C14-C19-O6
17.0
74.9
11.8
Figure 4. Molecular pair stackings in the crystals: A, (-)-1‚a; B,
1‚b.
C13′-C14′-C15′-C16′
C13′-C14′-C17′-C18′
C13′-C14′-C19′-O6′
-17.0
-74.9
-11.8
occurred to give three products (Scheme 2). The main product
was a chiral condensation compound (3) with [R]20D -30 (from
MeCN, c 0.2, ethyl acetate) and a melting point of 155 °C (from
MeCN) in 35% ee and in 37% chemical yield. Minor products
were the achiral condensation product (4) and diphenylmethane
(5). Irradiation of the enantiomorphous crystals (+)-1‚a resulted
in the formation of 3 with [R]20D +30 (c 0.2, ethyl acetate) and
a melting point of 150 °C (from MeCN) in 33% ee and in 38%
yield. In contrast to the solid-state photoreaction, irradiation
of a solution of 1 and a in acetonitrile did not produce 3 but
gave instead the achiral condensation product 4 and 1,1,2,2-
tetraphenylethane (6) in 74% and 24% yield, respectively, at
complete conversion of a (Scheme 2).
Table 3 summarizes the influence of irradiation time, tem-
perature, and wavelength on the solid-state photoreaction,
examined by using single crystals (2-3 mg) of (-)-1‚a and
(+)-1‚a followed by HPLC analysis. The irradiation of (-)-
1‚a at 10 °C for 1 h gave (-)-3 in 36% ee and in 50% yield at
the conversions of 28% and 45% of 1 and a, respectively. The
photoreactivity was retained even at -70 °C with an ac-
companying slight decrease of the reaction rate and the yield
of 3. However, the ee value was not changed; almost constant
values of 33-39% ee were obtained for photolyses in the
temperature range 10 to -70 °C. This result is different from
those of the several reports,19,20,23 in which absolute asymmetric
[2+2] photocycloaddition at lower temperature led to higher
ee values due to a decrease of the thermal motion in the crystals.
Prolonged irradiation for 5 h led to high conversion of 1 and a
(52% and 71%, respectively) and to a low yield of 3 due to
partial decomposition. However, even in this case the ee value
was unchanged. In addition, the reaction could be brought about
by irradiation using not only UV light (290-390 nm) but also
visible light (>390 nm). The crystal 1‚a has an absorption band
at wavelength 200-450 nm, which is almost the sum of those
of the components 1 (200-450 nm) and a (200-300 nm).
Therefore this reaction can be induced by the excitation of the
acridine molecule 1 at >390 nm, and 1 acts as the excited
species in the crystal 1‚a (Scheme 3).
Figure 3. Molecular packing in the achiral crystal 1‚b of acridine (1)
and 2,2-diphenylpropionic acid (b).
head fashion with a distance of 5.46 Å along the c axis, while
two molecular pairs of 1 and b stack in a head-to-tail
arrangement with a center of symmetry. The reason that 1‚b
(B) cannot be arranged in a head-to-head stacking along an axis
as in (-)-1‚a is most probably due to the steric hindrance of
the bulky methyl group (van der Waals radius 1.8 Å) of the
molecule b.
Absolute Asymmetric Decarboxylating Condensation.
Crystals of (-)-1‚a prepared by seeding were pulverized and
irradiated with a 400 W high-pressure mercury lamp through
Pyrex glass (>290 nm transparent) under argon for 3 h at 15
°C on a preparative scale. Solid-state photodecarboxylation
Thus, the absolute asymmetric photodecarboxylating con-
densation of single crystals of (-)-1‚a and (+)-1‚a under various
conditions gave 3 in the constant ee value of about 35%. As
described above, this value coincides with the ee values of 33%
and 35% obtained by the photoreaction on a preparative scale
of crystals (-)-1‚a and (+)-1‚a, respectively, prepared by
seeding. However, chiral crystals of 1‚a prepared without

Generation of Chirality in a Two-Molecule Crystal
J. Am. Chem. Soc., Vol. 118, No. 48, 1996 12063
Scheme 2
Table 3. Photoreaction of the Chiral Single Crystal 1‚a
(-0.94), C20 and C27 (-0.44), C22, C25, C23 and C24 (-0.28)
(for numbering, see Figure 5). On the other hand, the shorter
distances between H2 and other atoms, estimated from the
crystallographic data, are 1.94, 3.13, 2.94, and 3.31 Å of H2-
N1, H2-C20, H2-C27, and H2-C28, respectively; other
distances are longer than 4 Å. Both higher charge density and
shorter distance are needed to the proton transfer in the crystal
lattice, different from that in solution. Hydroacridine radical
species 11 and 12, which satisfy the both conditions, should be
preferably produced with their higher stability. Next decar-
boxylation of 10 gives the diphenylmethyl radical (15). In the
crystal lattice of (-)-1a, the molecular pairs of 1 and a stack
along the c axis with a plane-to-plane distance of 5.46 Å to
form a column structure as shown in Figure 5. Radical coupling
between ‚C1 of 15 and ‚C29 of 12 over the shortest distance of
5.11 Å can occur with the highest priority to give (S)-(-)-3 as
the major enantiomer. Radical coupling of ‚C1 and ‚C26 over
a distance of 6.52 Å also produces (S)-(-)-3. On the other
hand, (R)-(+)-3 is formed as a minor enantiomer by the radical
coupling between ‚C1 of 15 and ‚C21 and ‚C30 of 12 over the
longer distances of 6.79 and 8.97 Å, respectively. The S:R ratio
is calculated as ca. 2:1 based on the experimental ee value of
ca. 35% ee. The radical coupling is necessarily accompanied
by a slightly larger movement of the radical species in the crystal
lattice, in contrast to the well-known topochemical [2+2]
photocycloaddition, for which a distance of less than 4 Å
distance is indispensable.30
irradiation
nm
290-390
(-)-1‚a -30 0.5 290-390
conversion (%) yielda (%)
ee (%)
3
crystal °C
(-)-1‚a 10
h
1
a
3
4
5
1
28
6
45
13
31
71
63
23
35
51
50
58
48
28
39
34
51
32
2
2
4
2
2
2
4
2
11 (-) 36
8
9
6
9
4
9
7
(-) 35
(-) 33
(-) 33
(-) 36
(-) 39
(+) 37
(+) 35
(-)-1‚a -30
(-)-1‚a -30
(-)-1‚a -30
(-)-1‚a -70
(+)-1‚a -30
(+)-1‚a -30
1
5
1
1
1
1
290-390
290-390
>390
290-390
290-390
>390
22
52
39
12
23
31
a Yield based on consumed a.
seeding afforded different ee values of 36%, 27%, 22% with
minus optical rotations and 20%, 24%, 30% and 33% with plus
rotations by irradiation in separate vessels. These results
indicate that crystals of both absolute configuration (-)-1‚a and
(+)-1‚a are deposited simultaneously from solution without
seeding. Therefore, the seeding method is necessary to prepare
crystals of a desired chirality.
Determination of the absolute configurations of the reactant
and the product is most important to discuss the reaction path
in the crystal lattice. The absolute configuration of (-)-1‚a is
already determined (Figures 1 and 2). The molecular structure
of (-)-3 could be determined by X-ray structure analysis of
{(-)-3}2‚MeOH (Table 1). However, because oxygen is not
sufficiently heavy for the determination of absolute configuration
by anomalous dispersion, a sulfur atom was introduced by
preparing the trifluoromethanesulfate salt {(-)-7} of methylated
(-)-3, which did not affect the configuration of the asymmetric
carbon.28 The absolute configuration of (-)-7 could be
determined as (S) with a high degree of certainty by the Bijvoet
method based on the anomalous dispersion (∆f′′ ) 0.557 for
Cu KR radiation) of sulfur (Figure 5). The details are described
in the Experimental Section.
The reason why 4 and other condensation products are
scarcely produced in the solid-state photoreaction (Table 3) is
most probably due to the steric hindrance of the bulky radical
15, different from the solution reaction giving 4 in high yield.
In addition, the formation of 5 and the regeneration of 1 are
caused by hydrogen abstraction by the diphenylmethyl radical
15 from 11 because the ‚C1-H2 distance (3.11 Å) between
the radicals 15 and 11 is short enough to abstract the hydrogen
H2.7 The regeneration of 1 is the reason for the lower
conversion of 1 than that of a (Table 3).
How does the stereospecific condensation reaction occur?
Scheme 3 and Figure 5 show the possible reaction mechanism
and the radical coupling path, respectively. Irradiation of the
crystal excites 1 followed by electron transfer from a to 1 to
give a cation radical (8) and an anion radical (9). Proton transfer
can then afford diphenylacetate radical (10) and hydroacridine
radical species (11-14). The charge densities on 9 by semiem-
pirical PM329 in vacuum are localized in the order of N1
Conclusion
A chiral two-component molecular crystal composed of
acridine and diphenylacetic acid, which are achiral molecules,
could be prepared by a spontaneous crystallization from an
acetonitrile solution. The two-component molecular crystal is
(28) Beard, C. D.; Baum, K.; Grakauskas, V. J. Org. Chem. 1973, 38,
3673-3677.
(29) Stewart, J. J. J. Comput. Chem. 1989, 10, 209-264.
(30) (a) Cohen, M. D.; Schmidt, G. M. J. J. Chem. Soc. 1964, 1996-
2000. (b) Schmidt, G. M. J. Pure Appl. Chem. 1971, 27, 647-678.

12064 J. Am. Chem. Soc., Vol. 118, No. 48, 1996
Koshima et al.
Scheme 3
Figure 5. Radical coupling path in the crystal (-)-1‚a.
determining the products on a Waters HPLC system. All the reagents
were commercially available.
photoreactive, and an absolute asymmetric synthesis was
successfully achieved by a photodecarboxylating condensation.
This work represents a new step in the chiral crystallization of
achiral molecules in a two-component system and in solid-state
absolute asymmetric synthesis by utilizing a bimolecular process.
Preparation of Two-Component Molecular Crystals (1‚a and 1‚b)
of Acridine (1) and Acids (a and b). The chiral two-component
molecular crystal 1‚a was prepared by slow evaporation of 1:1 solution
of 1 and a in MeCN at room temperature. (-)- and (+)-1‚a could be
prepared by the seeding. The crystal 1‚b was prepared by evaporating
the 1:1 solution of 1 and b in EtOH at room temperature.
(-)- or (+)-1‚a: light yellow crystal; mp 100-102 °C; IR (KBr)
2490-3085, 1705 cm-1; UV 190-450 nm. Anal. Calcd for C27H21-
NO2 (1:1): C, 82.84; H, 5.42; N, 3.58. Found: C, 83.26; H, 5.64; N,
3.57.
1‚b: dark yellow crystal; mp 138-140 °C; IR 2465-3100, 1700
cm-1; UV 190-450 nm. Anal. Calcd for C28H23NO2 (1:1): C, 82.93;
H, 5.73; N, 3.45. Found: C, 83.00; H, 5.86; N, 3.36
Solid-State Photoreaction of Chiral Crystal 1‚a. (-)-1‚a (800
mg) in preparative scale prepared by seeding was pulverized, placed
between two Pyrex plates, and irradiated with a 400 W high-pressure
Experimental Section
General Methods. 1H NMR spectra were measured on a 60 MHz
JEOL PMX-60 spectrometer with tetramethylsilane as an internal
standard. IR spectra were recorded on a JASCO FT/IR-8300 spectro-
photometer. UV spectra were measured on a Shimadzu UV-3100 and
spectrophotometer. UV spectra in solid state were also taken on a
Shimadzu MPS 2000 spectrophotometer by a reflection method.
Differential scanning calorimetry (DSC) was done on a Rigaku
Thermoflex TAS-200 DSC8230D, and melting points (mp) were not
corrected. Elemental analysis was carried out with a Yanaco CHN
Corder MT-5. HPLC with a photodiode-array detector was used for

Generation of Chirality in a Two-Molecule Crystal
J. Am. Chem. Soc., Vol. 118, No. 48, 1996 12065
mercury lamp for 3 h under argon at room temperature. The irradiated
mixture was submitted to preparative TLC (7:1 benzene-ethyl acetate)
to give 260 mg of a chiral condensation product 3 in 37% yield and 15
mg of 4 in 2% yield. Pure enantiomers of 3 were separated by HPLC
with a Daicel Chiralpak AD preparative column eluting with 2%
2-propanol in hexane. Next recrystallization of (-)-3 and (+)-3 from
MeCN-MeOH gave the high quality crystals of {(-)-3}2‚MeOH and
{(+)-3}2‚MeOH, respectively.
crystallographic analysis. Although oxygen is a light atom (∆f′′ )
0.032 for Cu KR radiation), its use as an anomalous scatterer was
preferred, because even slight modification of (-)-1‚a by induction of
heavier elements such as sulfur and chlorine may cause changes in the
initial crystal structure. One of the single crystal cut into two pieces:
half was subjected to reaction, yielding the photoproduct (-)-3 in 33%
ee (measured by HPLC using a chiral column). It was thus classified
to be (-)-1‚a. The second half was fitted to the top of the glass rod
and made into a spherical crystal (0.5 mm diameter) by rubbing the
surface with a wet cloth in MeCN. Since the space group is P212121,
equivalent Miller indices are (hkl), (h kh hl), (hh k hl), (hh kh l) at the plus
side and (hh kh hl), (hh k l), (h kh l), (h k hl) at the minus side. However,
structure factors Fo containing hl of Miller indices were omitted in this
evaluation in order to avoid errors due to the absorption of X-ray by
the glass rod at minus position of ø-circle. Twenty-five reflections of
the Bijvoet pairs were selected in order of larger absolute value {0.75
> |∆Fc|/σ(Fo) > 0.28}. The diffraction intensities were measured
manually in a low speed due to the weakness of diffraction intensities.
By comparisons of ∆Fo/σ(Fo) vs ∆Fc/σ(Fo) for Bijvoet pairs, 22
reflections (88%) of 25 gave opposite plus and minus signs. This result
indicates that the absolute configuration is not correct with a high degree
of certainty.26 Therefore, x, y, and z axes were converted; Figures 1,
2, and 5 show correct absolute configuration of (-)-1‚a.
Single crystals of {(-)-3}2‚MeOH were obtained by recrystallization
from the solution of (-)-3 in MeCN-MeOH and the crystal structure
could be determined by X-ray crystallography (Table 1). However,
because oxygen is an insufficiently heavy atom to determine the
absolute configuration by Bijvoet method, a sufficiently heavy sulfur
atom (∆f′′ ) 0.557 for Cu KR radiation) was introduced in the form
of the salt (-)-7 (mp 135 °C, [R]20D -91, c 0.2, MeCN) of methylated
(-)-3 with trifluoromethanesulfonate,28 which reaction did not change
the configuration of the asymmetric carbon of (-)-3. The salt (-)-7
was prepared by reacting (-)-3 with methyl trifluorosulfate in CH2Cl2
followed by recrystallization from CH2Cl2. The crystal had a chiral
space group P21 (Table 1). The fluorine atoms of trifluoromethane-
sulfate were slightly disordered in the crystal. The comparison of ∆Fo
vs ∆Fc for Bijvoet pairs resulted in correct trend to be (S)-(-)-7 with
41 reflections (80%) of 51 for 2.0 > |∆Fc|/σ(Fo). Therefore the absolute
configuration of (-)-3 could be successfully determined to be (S)-
(-)-3 (Figure 5).
3: white crystal, mp 154-155 °C (from MeCN); [R]20D -30 (c 0.2,
THF); 35% ee (HPLC equipped with a Daicel Chiralpak AD column,
2% 2-propanol in hexane as an eluant); IR (KBr) no NH band; 1H
NMR (THF-d8) δ 6.90-7.90 (m, 15H), 6.50 (dd, J 9.0, 1.5 Hz, 1H),
5.83 (dd, J 9.0, 3.0 Hz, 1H), 2.80-4.00 (m, 2H); UV (MeCN) λmax
224 (log ꢀ 4.61), 254 (4.67), 283 (4.18), 327 (3.76), 343 (3.79) nm.
Anal. Calcd for C26H21N: C, 89.88; H, 6.09; N, 4.03. Found: C,
90.22; H, 6.26; N, 3.92.
{(-)-3}2‚MeOH: white crystal, mp 135-137 °C (from MeOH-
MeCN); [R]20D -121 (c 0.4, THF); optical purity 100%. Anal. Calcd
for C53H46N2O: C, 87.55; H, 6.39; N, 3.85. Found: C, 87.65; H, 6.15;
N, 3.90.
{(+)-3}2‚MeOH: white crystal, mp 132-135 °C (from MeOH-
MeCN); [R]20 +123 (c 0.2, THF); optical purity 100%.
D
HPLC Study of Solid-State Photoreaction. One single crystal
(2-3 mg) was pulverized, placed between two Pyrex plates and
irradiated with a 500 W xenon short arc lamp through a UV transparent
filter (290-390 nm irradiation) or a UV cut filter (>390 nm irradiation)
under argon at appropriate temperatures and times. In the cases of the
crystals prepared by seeding or evaporation, 20 mg of powdered crystals
was irradiated. The irradiated sample was methylated with CH2N2
followed by HPLC analysis (C18 column, methanol-water). The results
are shown in Table 3.
Preparative Photoreaction of 1 with a in MeCN. A solution of
1 (895 mg, 5 mmol) and a (1060 mg, 5 mmol) in MeCN (100 mL)
was internally irradiated with a 100 W high-pressure mercury lamp
for 2 h under argon at room temperature. After the irradiation, a
precipitated product 4 (1270 mg) was separated by filtration of the
reaction mixture in 74% yield. The filtrate was submitted to preparative
TLC (7:1 benzene-ethyl acetate) to give 6 (200 mg) in 24% yield.
1
The mp (215-216 °C), IR, and H NMR signals were in accordance
to those of the authentic sample.
4: white needle, mp 254-255 °C (from THF-MeCN); IR 3375
cm-1 1H NMR could not be measured due to the low solubility in
.
Acknowledgment. We thank Dr. Motoo Shiro (Rigaku
Corp.) for helpful discussion with X-ray crystallographic data
analysis. This work was partly supported by a Grant-in-Aid
for scientific research from the Ministry of Education, Science
and Culture, Japan. K.D. is a guest researcher from Zhengzhou
University, China.
any solvent. Anal. Calcd for C26H21N: C, 89.88; H, 6.09;, N, 4.03.
Found: C, 90.12; H, 6.30; N, 3.87.
X-ray Structure Analyses. Data collections were performed on a
Rigaku AFC7R automatic four-circle X-ray diffractometer equipped
with a graphite monochromated Mo KR (λ ) 0.710 69 Å) or Cu KR
(λ ) 1.541 78 Å) radiation and a rotating anode. Absorption correction
was applied. No degradation of the crystal by X-ray was ascertained
in all cases by repeated monitoring of the three representative reflections
every 150 reflections. These structures were solved by direct methods
and expanded using Fourier techniques. The non-hydrogen atoms were
refined anisotropically. Atomic parameters were refined by the full-
matrix least-squares method at the final stage. All the calculations were
carried out on teXsan crystallographic software package, Molecular
Structure Corp. Detail crystal data are summarized in Table 1.
The absolute configuration of (-)-1‚a was determined very carefully
by the Bijvoet method using anomalous despersion during X-ray
Supporting Information Available: Tables giving full data
collection parameters and further details of refinement, atomic
coordinates, anisotropic displacement parameters, bond lengths
and angles, torsion angles of four structures reported in this
paper (107 pages). See any current masthead page for ordering
and Internet access instructions.
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