Absolute asymmetric photoreactions of acridines with diphenylacetic acid in their cocrystals

Article abstract of DOI:10.1080/15421400590958520

Solid-state photodecarboxylation occurs in a chiral cocrystal of acridine and diphenylacetic acid to afford a chiral condensation product in modest enantiomeric excess. A chiral cocrystal of 9-methylbenz[c]acridine and diphenylacetic acid also undergoes similar photodecarboxylation but gives an almost racemic product. The different enantioselectivities between the two chiral cocrystals can be understood on the basis of the molecular arrangements in the lattice.

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Absolute Asymmetric
Photoreactions of Acridines
with Diphenylacetic Acid in
their Cocrystals
Hideko Koshima a
a Department of Applied Chemistry , Faculty of
Engineering, Ehime University , Matsuyama, Japan
Published online: 31 Aug 2006.
To cite this article: Hideko Koshima (2005) Absolute Asymmetric Photoreactions of
Acridines with Diphenylacetic Acid in their Cocrystals, Molecular Crystals and Liquid
Crystals, 440:1, 207-214, DOI: 10.1080/15421400590958520
To link to this article: http://dx.doi.org/10.1080/15421400590958520
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Mol. Cryst. Liq. Cryst., Vol. 440, pp. 207–214, 2005
Copyright # Taylor & Francis Inc.
ISSN: 1542-1406 print=1563-5287 online
DOI: 10.1080/15421400590958520
Absolute Asymmetric Photoreactions of Acridines with
Diphenylacetic Acid in their Cocrystals
Hideko Koshima
Department of Applied Chemistry, Faculty of Engineering, Ehime
University, Matsuyama, Japan
Solid-state photodecarboxylation occurs in a chiral cocrystal of acridine and
diphenylacetic acid to afford a chiral condensation product in modest enantio-
meric excess. A chiral cocrystal of 9-methylbenz[c]acridine and diphenylacetic acid
also undergoes similar photodecarboxylation but gives an almost racemic product.
The different enantioselectivities between the two chiral cocrystals can be under-
stood on the basis of the molecular arrangements in the lattice.
Keywords: absolute asymmetric photoreactions; acridine; cocrystals; diphenylacetic
acid; 9-methylbenz[c]acridine; photodecarboxylation
INTRODUCTION
Absolute asymmetric synthesis by solid-state reaction of a chiral crys-
tal spontaneously formed from achiral molecules is a promising meth-
odology for asymmetric synthesis [1–3]. Since our success in absolute
asymmetric photodecarboxylative condensation of acridine (1) with
ꢀ
diphenylacetic acid (a) in the chiral cocrystal (1 a) [4], we would like
to design new cases of absolute asymmetric synthesis with high
reliability. However, spontaneous chiral crystallization cannot be pre-
dicted at the present time [5,6]. Hence, we have prepared several ser-
ies of chiral cocrystals by combining two different achiral molecules,
based on the working hypothesis that chiral crystallization can occur
by freezing two molecules into chiral conformations through hydrogen
This work was supported by a Grant-in-Aid for Scientific Research from the Ministry
of Education, Culture, Sports, Science, and Technology of Japan and the Kurata
Memorial Hitachi Science and Technology Foundation.
Address correspondence to Hideko Koshima, Department of Applied Chemistry, Faculty
of Engineering, Ehime University, Matsuyama 790-8577, Japan. E-mail: koshima@
eng.ehime-u.ac.jp
207

208
H. Koshima et al.
ꢀ
bonding [7–10]. Recently we found a chiral cocrystal (2 a) of 9-methyl-
benz[c]acridine (2) with diphenylacetic acid (a), but the solid-state
photoreaction afforded an almost racemic condensation product,
rather than achieving absolute asymmetric synthesis [11]. Herein
ꢀ
ꢀ
the solid-state photoreactions in the chiral cocrystals 1 a and 2 a
are reviewed, and the difference of enantioselectivities is discussed
based on their molecular arrangements.
RESULTS AND DISCUSSION
The cocrystals incorporate acridine 1 or 9-methylbenz[c]acridine 2 as
electron acceptors and diphenylacetic acid a as an electron donor in
the photoreactions (Chart 1). Recrystallization of equimolar solutions
ꢀ
of the two components in acetonitrile gave ꢁthe chiral cocrystals 1 a or
ꢀ
2 a. Their melting points are 101 and 138 C, respectively. Seed crys-
ꢀ
ꢀ
tals of both enantiomorphous crystals of 1 a and 2 a were initially
obtained by spontaneous crystallization from slightly supersaturated
solutions in several vessels, and were easily discriminated by the
measurement of their solid-state circular dichroism (CD) spectra as
Nujol mulls (Fig. 1). Then the left and right handed crystals could
be separately prepared by seeding on a large scale. X-Ray crystallo-
ꢀ
ꢀ
graphic analysis of 1 a and 2 a confirmed the chiral nature of these
products whose space groups are P212121 and P1, respectively. Their
crystal data are summarized in Table 1. The absolute structure of
ꢀ
M-1 a was satisfactorily determined by the Bijvoet method based on
anomalous dispersion of the oxygen atom with Cu Ka radiation. The
ꢀ
CD spectrum of M-1 a corresponds to the curve M in Figure 1a. The
ꢀ
absolute structure of 2 a is not yet determined. Figure 2 shows
CHART 1 Chiral cocrystals.

Absolute Asymmetric Photoreactions in Cocrystals
209
ꢀ
FIGURE 1 Solid-state CD spectra of the enantiomorphous cocrystals (a) 1 a
ꢀ
and (b) 2 a.
ꢀ
ꢀ
the molecular arrangements in M-1 a and 2 a. Hydrogen bond pairs
ꢀ ꢀ ꢀ
between 1 or 2 and a are formed with H N distances of 1.79 or
˚
1.46 A. In both cocrystals, the diphenylacetic acid molecule has a pro-
ꢀ
peller-like conformation. The common feature of enantiomorphous 1 a
ꢀ
and 2 a is that only one type of molecular pair of the absolute configur-
ation forms noncentrosymmetrically in a unit cell (Z ¼ 4 and 1),
thereby inducing the crystal chirality (Fig. 3). Namely, the molecules
in themselves are achiral but the molecular shapes are frozen in chiral
forms within the lattice.
TABLE 1 Crystal Data of the Chiral Cocrystals
ꢀ
ꢀ
ꢀ
ꢀ
M-1 a
1 b
((S)-3)2 MeOH
7 MeOH
Formula
Space group
C27H21NO2
P212121
14.908(4)
25.367(6)
5.457(3)
90.0
90.0
90.0
2063(1)
4
C32H25NO2
P1
C53H46N2O
P1
C32H29NO
Pbca
18.995(1)
12.2607(6)
21.294(1)
90.0
90.0
90.0
4959.3(4)
8
˚
a, A
5.683(1)
9.110(2)
12.111(2)
101.443(6)
98.399(6)
103.08(1)
586.5(2)
1
9.871(1)
17.6408(9)
6.1787(9)
90.280(7)
107.31(1)
101.002(6)
1006.1(2)
1
˚
b, A
˚
c, A
a, deg
b, deg
c, deg
3
˚
V, A
Z
R
0.043
0.061
0.033
0.073
Rw
0.058
0.144
0.050
0.228

210
H. Koshima et al.
ꢀ
FIGURE 2 Molecular arrangements in the chiral cocrystals (a) 1 a and
ꢀ
(b) 2 a.
ꢀ
Crystals of M-1 a were pulverized, placed between two Pyrex plates
and irradiated with a 400 W high-pressure mercury lamp under argon
for 3 h at 15ꢁC on a preparative scale. Solid-state photodecarboxylation
occurred to give three products (Scheme 1). The main product was a
chiral condensation product ((S)-(–)-3) in 35% ee and 37% chemical
yield, achieving absolute asymmetric synthesis. Minor products were
the achiral condensation product (4) and diphenylmethane (5). The
ꢀ
ꢀ
FIGURE 3 Molecular pairs in the chiral cocrystals (a) M-1 a, (b) P-1 a,
ꢀ
ꢀ
(c) enantiomorphous 2 a and (d) opposite handed 2 a to (c).

Absolute Asymmetric Photoreactions in Cocrystals
211
SCHEME 1 Photoreaction of 1 with a in the chiral cocrystals and in the
solution.
absolute configuration of 3 was successfully determined as S by
X-ray anomalous dispersion of the sulfur atom of the trifluorometha-
nesulfonate salt of methylated (–)-3. Irradiation of the opposite crys-
ꢀ
tals, P-1 a, gave (R)-(þ)-3 in 33% ee and in 38% yield. In contrast,
solution photolysis of 1 with a in acetonitrile did not produce the chiral
product 3 but gave the achiral product 4 and 1,1,2,2-tetrapheny-
lethane (6) in 74% and 24% yield, respectively. Namely, the pro-
duction of 3 is specific to the solid-state photoreaction.
ꢀ
Enantiomorphous cocrystals of 2 a prepared by seeding (CD curve A
in Figure 1b) were also irradiated with a 400 W high-pressure mercury
lamp under argon for 4 h at 15ꢁC on a preparative scale (Scheme 2). Simi-
ꢀ
lar photodecarboxylation to 1 a occurred and afforded four products.
Chiral condensation product (7) was obtained in 13% chemical yield
SCHEME 2 Photoreaction of 2 with a in the chiral cocrystals and in the
solution.

212
H. Koshima et al.
but the enantiomeric excess was almost 0% ee. The main product was
diphenylmethane 5 in 34% yield, and the other minor products were tet-
raphenylethane 6 and benzophenone (8) in 3% and 13%, respectively.
ꢀ
Irradiation of the opposite handed crystals of 2 a also afforded almost
racemic 7. Therefore we conclude that absolute asymmetric synthesis
ꢀ
was not achieved in the enantiomophous cocrystals of 2 a.
On the other hand, solution photolysis of 2 and a in acetonitrile
afforded racemic 7 as the main product in 53% yield, and 4 and 5 in
2% and 12% yields, showing different reactivity and product selec-
tivity from the solid-state photoreaction. The molecular structure of
7 was confirmed by X-ray crystallographic analysis using a single crys-
tal of the 1:1 inclusion complex of racemic 7 with MeOH.
The reasons for successful and unsuccessful absolute asymmetric
ꢀ
ꢀ
reactions in the chiral crystals 1 a and 2 a can be discussed based
on the possible reaction mechanism (Scheme 3) and the coupling paths
ꢀ
ꢀ
(Fig. 4). Irradiation of 1 a or 2 a can cause electron transfer from a to
1 or 2 followed by proton transfer to afford a carboxylate radical (9)
and hydroacridine radical (10) or (11) [4,11]. Then decarboxylation
ꢀ
of the carboxylate radical yields a CHPh2 diphenylmethyl radical
ꢀ
(12). Next, radical coupling between the CHPh2 radical 12 and the
hydroacridine radical 10 or 11 produces 3 or 7.
ꢀ
In the crystal M-1 a, two directions for the radical coupling are
possible, which are shown by thick and thin arrows in Figure 4a.
The absolute configuration of 3 obtained by front attack with the
˚
shorter distance (5.1 A) gives the (S)-form in higher priority than
ꢀ
SCHEME 3 Possible reaction mechanism in the chiral cocrystals 1 a and
ꢀ
(b) 2 a.

Absolute Asymmetric Photoreactions in Cocrystals
213
ꢀ
FIGURE 4 Possible reaction paths in the chiral cocrystals (a) M-1 a and
ꢀ
(b) 2 a.
˚
the (R)-form by back attack involving the longer distance (6.8 A). The
S:R ratio is calculated as around 2:1 based on the experimental ee
value of 35% ee. On the other hand, in the enantiomorphous crystal
ꢀ
2 a, four radical coupling paths are possible (Fig. 4b). The absolute
configuration of 7 obtained by frontal attack (thick arrow) with the
˚
shortest distance (4.4 A) is opposite to that obtained by the three back
˚
attacks (thin arrows) involving longer distances (6.4, 6.5 and 6.5 A).
This results in the formation of an almost 1:1 racemic mixture of
(S)- and (R)-7. In conclusion, enantioselectivities in chiral crystals
are very much controlled by the precise molecular arrangements
present.
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