Oxiranes having an acridane structure as a novel chemiluminescent precursor: Synthesis and chemiluminescent studies

Article abstract of DOI:10.1016/S0040-4020(01)00216-2

Oxirane derivatives having acridane and adamantane structures were designed as a novel chemiluminescent precursor and were found to have a characteristic chemiluminescent ability which is introduced by a two-step trigger reaction involving treatment with alkaline H₂O₂ and subsequent acidic treatment. Structural study of the oxirane derivatives showed that the CIEEL mechanism is involved in this chemiluminescent reaction and it was also found that the chemiluminescent profile is affected by the kind of acid employed in the trigger reaction.

Full text of DOI:10.1016/S0040-4020(01)00216-2

TETRAHEDRON
Pergamon
Tetrahedron 57 62001) 33ꢀ1±33ꢀ7
Oxiranes having an acridane structure as a novel
chemiluminescent precursor: synthesis and
chemiluminescent studies
a
Kazuyuki Miyashita, Masatoshi Minagawa, Yohko Ueda, Yukie Tada, Nobuhiro Hoshino
a
a
a
b
a,p
and Takeshi Imanishi
a
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
b
Iatron Laboratories, Inc., 1460-6 Mitodai, Takocho, Katori-gun Chiba 289-2247, Japan
Received 12 January 2001; accepted 21 February 2001
AbstractÐOxirane derivatives having acridane and adamantane structures were designed as a novel chemiluminescent precursor and were
found to have a characteristic chemiluminescent ability which is introduced by a two-step trigger reaction involving treatment with alkaline
H O and subsequent acidic treatment. Structural study of the oxirane derivatives showed that the CIEEL mechanism is involved in this
2 2
chemiluminescent reaction and it was also found that the chemiluminescent pro®le is affected by the kind of acid employed in the trigger
reaction. q 2001 Elsevier Science Ltd. All rights reserved.
1
. Introduction
Sakanishi and his co-workers reported an interesting
example, namely, that light emission was observed during
the oxidation of 9-arylmethylene-10-methylacridane 1 with
an excess of m-chloroperbenzoic acid 6m-CPBA) or
An analytic method using chemiluminescent compounds
has attracted much attention as a promising tool for detec-
tion of a small quantity of biomacromolecules. Intensive
1
3
dimethyldioxirane 6DMD). They proposed that b-hydroxy-
studies on various chemiluminescent peroxy derivatives
such as 1,2-dioxetanes have been reported and, in fact,
alkyl peroxyesters or 1,2,4-trioxanes generated in situ via
unstable oxiranes 2 are involved as the key intermediates
and would be decomposed via a chemically initiated
electron exchange luminescence 6CIEEL) mechanism. It
occurred to us that an oxirane ring system could be
stabilized by introducing a bulky substituent, such as an
2
some 1,2-dioxetane derivatives are known to exhibit high
light-emission ability. However, there still remain problems
to be resolved before they can be employed as a versatile
method: the level of their stability does not permit easy
handling. For such purposes, the compound would desirably
be stable enough and, in addition, would desirably be
designed not only as to be able to induce strong
chemiluminescence by a trigger reaction, but also as to be
able to control the chemiluminescent pro®le by the
reaction conditions or by an inherent property of the
compound.
4
adamantane moiety, thereby rendering it a more potent
precursor for chemiluminescence than a dioxetane ring
5
system. According to this idea, we designed some oxirane
derivatives 3 and herein describe the preparation of these
oxiranes 3a±f and their chemiluminescence which is
speci®cally induced by a unique trigger reaction involving
ꢀ
oxidative treatment followed by acidic treatment 6Fig. 1).
Figure 1. Structures of compounds 1±3.
Keywords: chemiluminescence; oxiranes; epoxides; dioxetanes.
Corresponding author. Tel.: 181-ꢀ-ꢀ879-8200; Fax 181-ꢀ-ꢀ879-8204; e-mail: imanishi@phs.osaka-u.ac.jp
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020601)0021ꢀ-2

33ꢀ2
K. Miyashita et al. / Tetrahedron 57ꢀ2001) 3361±3367
Scheme 1.
Table 1. Chemiluminescent intensity for the oxiranes 3a±f
a
b
3 c
Run
Oxirane 3
Additive 6at 0 s)
Amounts of HCl 6at 25 s)
TRLU 6£10 )
1
2
3
4
5
ꢀ
7
8
3a
3a
3a
3b
3c
3d
3e
3f
m-CPBA in CH Cl
2
2
None
None
,10
,10
30ꢀ5
2047
320
57
Alkaline H
Alkaline H
Alkaline H
Alkaline H
Alkaline H
Alkaline H
Alkaline H
2
2
2
2
2
2
2
O
2
O
2
O
2
O
2
O
2
O
2
O
2
0.10 M, 0.1 ml
0.10 M, 0.1 ml
0.10 M, 0.1 ml
0.10 M, 0.1 ml
0.10 M, 0.1 ml
0.10 M, 0.1 ml
,10
2ꢀ
a
27
A solution of 3 in DMSO 61.0£10 M, 0.10 ml) was used.
b
c
A solution of H
Total relative light units 6TRLU) integrated for 120 s.
2 2
O in 0.1 M aqueous NaOH 60.1 M, 0.1 ml) was used.
2
. Results and discussion
emission was not detectable under the conditions 6run 1).
On treatment of 3a with an alkaline hydrogen peroxide
The oxirane derivatives 3 were easily synthesized as
follows. Ole®ns 6 were obtained by the McMurry reaction
of aromatic ketones 4 with 2-adamantanone 65). The ole®ns
6H O ) solution, rapid decomposition was observed on the
2 2
TLC, but in this case as well there was no intense chemi-
luminescence 6run 2). On the other hand, when hydrochloric
6
were treated with a slight excess of m-CPBA in dichloro-
acid was added after 25 s delay from the alkaline H O
2 2
methane at room temperature, giving oxiranes 3 in good
yields. Although isolation of the oxiranes 2 was reported
to be impossible, the oxiranes 3a±f were able to be puri®ed
by silica gel column chromatography and were quite stable
allowing handling under ambient conditions as expected
treatment, quick and strong light emission was detectable
as shown in Fig. 26run 3) accompanying the formation of
ketones 4a and 5. The chemiluminescent intensity was not
affected by the delay time in a range 20±180 s. In order to
investigate the effect of the nitrogen at X, the other oxiranes
3b±f were also examined under the same conditions 6runs
3
6
Scheme 1).
4
treatment with alkaline H . The chemiluminescent inten-
±8). The oxiranes 3b±f were also decomposed rapidly by
O
2 2
At ®rst, the luminescent property of 3a was examined, and
the results are outlined in Table 1. According to Sakanishi's
sity of the N-methyl derivative 3b was weaker than that of
3a. The introduction of an electron-withdrawing group on
the nitrogen 63c and d), however, further decreased the light
emission 6runs 5 and ꢀ). The compounds 3e and f, neither of
which has a nitrogen, were almost inert 6runs 7 and 8).
These ®ndings indicate the signi®cant role of the electron-
donating property of the nitrogen for the chemilumines-
cence.
3
report, oxirane 3a was further oxidized with m-CPBA in
a
various solvent systems. However, remarkable light
The amount of HCl was also found to affect the intensity of
the light emission. When 1 equiv. of the acid to the base was
added, the strongest light emission was obtained as shown in
Fig. 3. The chemiluminescent quantum yield 6FCL) was
estimated to be 0.0018, based on that of luminol
6
FCLˆ0.011) and is ca. 4000 times stronger than that of
3
a
the ole®n 1 6ArˆPh) reported by Sakanishi. The use of
excess HCl drastically decreased the light emission, which
is probably due to the protonation at the nitrogen by the
excess HCl.
Figure 2. Light-emission pro®les of 3a in DMSO by treatment with alka-
and subsequent with HCl.
line H
2
O
2
Next, we measured the chemiluminescent intensity of 3a by

K. Miyashita et al. / Tetrahedron 57ꢀ2001) 3361±3367
33ꢀ3
Figure 5. Chemiluminescent intensity for 3a in dioxane induced by cis- and
trans-cyclopropanedicarboxylic acids.
Figure 3. Relationship between the chemiluminescent intensity for 3a in
DMSO and the amount of HCl.
using various mineral and organic acids in place of HCl and
found that the chemiluminescent intensity depends on the
kind of acid used. Among the acids examined, oxalic acid
afforded stronger chemiluminescence than did HCl. The
amount of oxalic acid also affected the intensity, and the
strongest chemiluminescence was observed when 2equiv.
of oxalic acid to NaOH in alkaline H O was added.
Because two factors, the acidity and structural feature,
were thought to be related to this chemiluminescence, we
focused on the dicarboxylic acids having a different
methylene length in order to clarify this point. As shown
in Fig. 4, the chemiluminescent intensity appeared to
depend on the methylene length rather than the acidity.
Malonic acid 6nˆ1) was the best choice to obtain the
strongest chemiluminescence.
xymethyl, methyl, and aminomethyl groups, respectively
6Fig. ꢀ). Interestingly, hydroxyacetic acid afforded almost
the same chemiluminescent pattern and stronger intensity
upon comparison with oxalic acid. However, acetic acid was
less effective and its chemiluminescent pattern was some-
what different from those of oxalic and hydroxyacetic acids.
These results show that the `OH' function increases the
chemiluminescence, and the hydroxymethyl group, in
place of one of the two carboxyl groups, plays the same
role more effectively. In contrast, glycine afforded a quite
different chemiluminescent pattern as shown. Although it
was weak, detectable light-emission by a photon counter
was continued even after 15 min. It is note worthy that
the total value of the relative light units induced by
glycine for 120 s is low, but that for 15 min approaches
the value induced by oxalic acid for 120 s. This suggests
that the total amount of the intermediate formed by glycine
is almost the same as that by oxalic acid, only its rate is
2
2
To establish more clearly the structural in¯uence of
dicarboxylic acids, cis- and trans-1,2-cyclopropanedi-
carboxylic acids, regarded as conformationally restricted
succinic and glutalic acids 6nˆ2and 3), were also
examined. As shown in Fig. 5, the cis-acid afforded stronger
chemiluminescence than the trans-acid. In particular, the
chemiluminescent intensity by succinic acid was in the
range of those by cis- and trans-acids. These results strongly
suggest that the distance between the two carboxyl groups
plays a signi®cant role.
8
slower.
Taking into account all the results described above, we
considered the chemiluminescent process of 3a to be as
shown in Scheme 2. At ®rst, the oxirane ring is most likely
to be attacked by the hydroperoxy anion to form a-hydro-
peroxy alcohol 7. The following acidic treatment of 7 would
lead to the following two pathways: 6i) decomposition from
the anti-conformation anti-7 could give ketones 4a and 5;
6ii) formation of the dioxetane 8 from the syn-conformation
syn-7 could occur by participation of the neighboring
The role of the carboxyl group was then studied by replacing
one of the two carboxyl groups of oxalic acid with hydro-
9
hydroxy group. Since a 1,2-dioxetane structure is known
to be decomposed via a CIEEL mechanism to form an
1
0
excited ketone which emits light, the latter pathway
appears to be responsible for the present chemilumines-
cence.
1
1
Although the details are not clear, the effect of the kind of
acid used also appears to support this mechanism and could
be explained as follows. The carboxylic acids having
another carboxyl group or a hydroxy group in their
proximity, like malonic acid and hydroxyacetic acid,
could interact favorably with the syn-conformation of
a-hydroperoxy alcohol syn-7 as represented by A and B
in Fig. 7 and, consequently, could increase the formation
7
Figure 4. Relationship between pK
HOOC±6CH
in dioxane induced by the acids.
a
values for dicarboxylic acids,
1
of the 1,2-dioxetane by effective H transfer from the
carboxyl group to the hydroperoxy group of syn-7, rather
2
)
n
±COOH 6nˆ0±4) and chemiluminescent intensity of 3a

33ꢀ4
K. Miyashita et al. / Tetrahedron 57ꢀ2001) 3361±3367
Figure 6. Chemiluminescent pro®le and intensity for 3a in dioxane induced by treatment with X±COOH.
Scheme 2.
Figure 7. Proposed interaction of syn-7 with malonic acid, hydroxyacetic acid or glycine.
than direct decomposition via anti-conformation of
a-hydroperoxy alcohol anti-7. In contrast, glycine appears
to exist as an ionized form mainly under the conditions
employed, but would exist as a non-ionized form as well
via equilibrium. Since interaction of the ionized form with
syn-7 cannot protonate the hydroperoxy function and thus,
the nucleophilicity of the hydroxy group is decreased as
illustrated by C, the 1,2-dioxetane would not be formed.
In contrast, a similar interaction of the non-ionized form
with syn-7 could protonate and also increase the nucleo-
philicity of the hydroxy group of syn-7 to form the 1,2-
dioxetane as shown by D. The weak but continuous light-
emission by the addition of glycine is most likely to be
explained by taking the interaction of the non-ionized
form gradually produced from the ionized form via the
equilibrium.

K. Miyashita et al. / Tetrahedron 57ꢀ2001) 3361±3367
33ꢀ5
In conclusion, we have demonstrated a novel example of
chemiluminescence which is speci®cally induced from a
novel precursor 3a having an oxirane structure and an
N-benzylacridane structure by a trigger reaction: alkaline
H O treatment and acidic treatment. The structural effect
25). Anal. Calcd for C H N: C, 89.29; H, 7.24; N, 3.47.
30 29
Found: C, 89.31; H, 7.32; N, 3.4ꢀ.
Other ole®ns were prepared according to the same
procedure.
2
2
of the oxirane derivatives on the chemiluminescence
showed that a CIEEL mechanism is involved in this chemi-
luminescence. It was also found that the chemiluminescence
from the oxirane 3a has an interesting feature namely that
the chemiluminescent pro®le can be changed by the kind of
acid used in the trigger reaction. The results shown in this
paper would demonstrate the oxirane 3a to be a potent
chemiluminescent probe for the analysis of biomacro-
molecules.
3
,7
3.1.2. 9,10-Dihydro-10-methyl-9-ꢀtricyclo[3.3.1.1 ]de-
cylidene)acridine ꢀ6b). 74% yield, colorless crystals, mp
25ꢀ±2578C 6AcOEt). IR n 6KBr): 2908, 1589, 14ꢀ1, 1339,
2
1
MeCN
12ꢀ9 cm . UV l nm 61): 340 6ꢀ000), 2ꢀ1 615000),
22ꢀ 629000). H NMR 6CDCl ) d: 1.40±2.40 612H, m), 3.41
max
1
3
63H, s), 3.40±3.48 62H, m), ꢀ.98 64H, td, Jˆ7, 1 Hz), 7.15±
1
3
7.2ꢀ 64H, m). C NMR 6CDCl ) d : 2ꢀ.8±29.4 6m), 32.2,
3
C
33.3, 37.2, 38.0±41.0 6m), 111.9, 119.9, 120.3, 12ꢀ.1, 12ꢀ.2,
1
7
27.2, 144.2, 144.8. Anal. Calcd for C H N: C, 88.03; H,
24 25
.ꢀ9; N, 4.28. Found: C, 87.93; H, 7.ꢀ7; N, 4.31.
3
,7
3
. Experimental
3.1.3. 9,10-Dihydro-10-phenyl-9-ꢀtricyclo[3.3.1.1 ]de-
cylidene)acridine ꢀ6c). 51% yield, colorless crystals, mp
254.5±255.58C 6AcOEt). IR n 6KBr): 290ꢀ, 284ꢀ, 14ꢀꢀ,
3
.1. General
2
1
MeCN
1
452, 1278, 751 cm UV lmax nm 61): 340 610000),
28ꢀ 615000), 25ꢀ 621000), 228 647000). H NMR 6CDCl )
3
1
Melting points 6mps) were taken on a Yanagimoto micro-
melting point apparatus and are uncorrected. Infrared spec-
tra were measured on a JASCO FT/IR-200 Fourier-transfer
infrared spectrometer. H NMR spectra were measured on a
JEOL EX-270 6270 MHz) spectrometer and tetramethyl-
silane 6TMS) was used as an internal standard. C NMR
spectra were measured on a JEOL EX-270 6ꢀ7.8 MHz)
spectrometer with CDCl3 as an internal standard
d: 1.80±2.10 612H, m), 3.50 62H, br s), ꢀ.44 62H, dd, Jˆ8,
13
1 Hz), ꢀ.85±7.05 64H, m), 7.20±7.35 62H, m), 7.39 62H, dd,
1
Jˆ7, 1 Hz), 7.49±7.ꢀ5 63H, m). C NMR 6CDCl
) d : 28.7,
3 C
32.1, 37.1, 39.7, 113.8, 120.0, 124.1, 125.8, 127.3, 128.1,
130.4, 131.3, 140.8, 144.4, 144.8. EI-MS m/z 6%): 389 6M ,
1
3
1
100). Anal. Calcd for C29
Found: C, 89.31; H, 7.24; N, 3.ꢀ2.
H27N: C, 89.42; H, ꢀ.99; N, 3.ꢀ0.
6
77.0 ppm). Electron-impact mass spectra 6EI-MS) were
3
,7
obtained by use of a JEOL JMS-700 mass spectrometer.
Chemiluminescent intensity was monitored on a Berthold
Lumat LB 9501 photon counter. For silica gel column chro-
matography, E. Merck Kieselgel ꢀ0 60.0ꢀ3±0.200 mm) was
used. 10-Substituted 9610H)-acridones 4a, 4b, 4c
and 4d were prepared from 9610H)-acridone according
to literatures.
3.1.4. Ethyl 9,10-dihydro-9-ꢀtricyclo[3.3.1.1 ]decyli-
dene)-10-acridineacetate ꢀ6d). ꢀ3% yield, colorless
crystals, mp 214±21ꢀ8C 6AcOEt). IR n 6KBr): 2907,
2
1
MeCN
1751, 1591, 1458, 1188 cm . UV lmax
67900), 28ꢀ 610000), 258 61ꢀ000), 225 635000). H NMR
6CDCl
nm 61): 334
1
2a
12a
12b
1
1
2c
) d: 1.27 63H, t, Jˆ7 Hz), 1.40±2.30 612H, m), 3.45
3
62H, br s), 4.27 62H, q, Jˆ7 Hz) 4.ꢀ4 62H, s), ꢀ.77 62H, dd,
13
Jˆ8, 1 Hz), ꢀ.98 62H, td, Jˆ8, 1 Hz), 7.10±7.30 64H, m).
3
,7
.1.1. 10-Benzyl-9,10-dihydro-9-ꢀtricyclo[3.3.1.1 ]de-
3
cylidene)acridine ꢀ6a). Under a nitrogen atmosphere,
LiAlH 6383 mg, 10.1 mmol) was added to a stirred suspen-
4
C NMR 6CDCl ) d :14.2, 27.4±28.5 6m), 32.1, 37.1,
3 C
38.ꢀ±40.4 6m), 48.7, ꢀ1.3, 112.2, 119.9, 120.4, 12ꢀ.0,
12ꢀ.1, 127.4, 143.1, 144.7, 1ꢀ9.8. Anal. Calcd for
sion of TiCl 64.00 g, 20.1 mmol) under ice-cooling and the
3
C
H, 7.38; N, 3.42.
27
H
29NO
2
: C, 81.17; H, 7.32; N, 3.51. Found: C, 80.97;
stirring was continued for 10 min at the same temperature.
After addition of Et N 60.74 ml, 10.1 mmol) at room
3
3,7
temperature, the whole was re¯uxed for 1 h. To the reaction
mixture, a solution of N-benzylacridone 64a, 585 mg,
3.1.5. 9-Tricyclo[3.3.1.1 ]decylidene-9,10-dihydroanthra-
cene ꢀ6e). ꢀ4% yield, colorless crystals, mp 233.5±2358C
2
6AcOEt). IR n 6KBr): 2912, 14ꢀꢀ, 779, 738 cm . UV
1
2
.05 mmol) and 2-adamantanone 6308 mg, 2.05 mmol) in
MeCN
THF 615 ml) was added dropwise for 30 min and the re¯ux
was continued for 15 h. After cooling, the reaction mixture
was diluted with H O and extracted with AcOEt. The
l
max
nm 61): 2ꢀ2 61ꢀ000), 234 61ꢀ000), 234 615000),
1
210 628000). H NMR 6CDCl ) d: 1.54 61H, s), 1.50 62H, br
3
d, Jˆ12Hz), 1.75 6 2H , br d, Jˆ12Hz), 1.88 63H, br s),
2
organic layer was washed with H O and saturated NaCl
2
2.09±2.22 64H, m), 3.43 62H, s), 3.ꢀ9, 3.83 62H, AB q,
1
3
solution, dried over Na SO , and concentrated under
4
Jˆ1ꢀ Hz), 7.08±7.19 64H, m), 7.25±7.31 64H, m).
NMR 6CDCl ) d : 27.ꢀ, 28.4, 33.1, 37.1, 37.7, 39.5, 40.0,
125.1, 125.2, 125.4, 12ꢀ.ꢀ, 127.1, 138.7, 138.9. Anal. Calcd
C
2
reduced pressure. The resultant residue was puri®ed by
silica gel column chromatography 6CH Cl ±hexane, 1:1)
3
C
2
2
to give the title compound 6a 6ꢀ29 mg, 7ꢀ%) as colorless
crystals. mp 218±219.58C 6AcOEt). IR n 6KBr): 2908,
for C24
H
24: C, 92.2ꢀ; H, 7.74. Found: C, 92.20; H, 7.73.
2
589, 14ꢀ1, 1339, 12ꢀ9 cm . UV l
1
MeCN
3,7
3.1.6. 9-Tricyclo[3.3.1.1 ]decane-9H-¯uorene ꢀ6f). 29%
yield, colorless crystals, mp 23ꢀ±237.58C 6AcOEt). IR n
1
nm 61): 341
9000), 293 610000), 258 617000), 22ꢀ 641000). H NMR
max
1
6
6
6
2
1
MeCN
CDCl ) d: 1.40±2.40 612H, m), 3.40±3.52 62H, m), 5.23
3
2H, s), ꢀ.82 62H, dd, Jˆ8, 1 Hz), ꢀ.88±7.35 611H, m).
6KBr): 2917, 1ꢀ1ꢀ, 1ꢀ01, 1445 cm . UV lmax
nm
61): 320 61ꢀ000), 294 617000), 23ꢀ 647000). H NMR
6CDCl ) d: 2.00 62H, br s), 2.10 610H, br s), 4.07 62H, br
1
3
1
C
NMR 6CDCl ) d : 28.1, 32.2, 37.1, 39.1±40.3 6m), 50.4,
3
3
C
1
1
13.5, 120.0, 120.3, 12ꢀ.1, 12ꢀ.2, 12ꢀ.5, 12ꢀ.7, 127.2,
28.5, 137.2, 143.4, 144.5. EI-MS 6m/z, %): 404 6M 1H,
s), 7.20±7.35 64H, m), 7.78 62H, dd, Jˆ7, 2Hz), 7.88 6 2H ,
) d : 27.8, 35.9, 3ꢀ.8,
3 C
1
13
dd, Jˆꢀ, 2Hz). C NMR 6CDCl

33ꢀꢀ
K. Miyashita et al. / Tetrahedron 57ꢀ2001) 3361±3367
1
613000), 21ꢀ 62ꢀ000). H NMR 6CDCl ) d: 1.10 62H, br
39.5, 119.4, 124.4, 12ꢀ.2, 12ꢀ.7, 139.2, 139.7, 1ꢀ0.3. Anal.
Calcd for C H : C, 92.57; H, 7.43. Found: C, 92.71; H,
3
d, Jˆ12Hz), 1. 2ꢀ 63H, t, Jˆ7 Hz), 1.35±1.80 69H, m),
2
3
22
7
.41.
1.93 61H, br s), 2.10 62H, br d, Jˆ12 Hz), 4.2ꢀ 62H, q,
13
Jˆ7 Hz), 4.ꢀ7 62H, s), ꢀ.81 62H, d, Jˆ8 Hz), 7.026 2H , t,
C
0
tricyclo-[3.3.1.1 ]decane] ꢀ3a). To a stirred solution of
0
00
3
.1.7. 10-Benzyldispiro[acridine-9ꢀ10H),2 -oxirane-3 ,2 -
Jˆ8 Hz), 7.20±7.30 62H, m), 7.3ꢀ 62H, dd, Jˆ8, 2Hz).
3
,7
NMR 6CDCl ) d : 14.2, 2ꢀ.ꢀ, 27.0, 30.2, 34.9, 35.9, 3ꢀ.4,
3 C
6
a 6500 mg, 1.24 mmol) was added m-CPBA 670%,
3ꢀ mg, 1.3ꢀ mmol) at room temperature and the stirring
48.3, ꢀ1.4, ꢀꢀ.1, 111.ꢀ, 120.4, 122.ꢀ, 125.4, 127.4, 142.8,
1ꢀ9.5. EI-MS m/z 6%): 41ꢀ 6M , 37). Anal. Calcd for
1
3
was continued for 15 min at the same temperature. After
C H NO: C, 78.04; H, 7.03; N, 3.37. Found: C, 77.92;
2
7
29
addition of saturated NaHCO solution, the reaction mixture
3
H, 7.03; N, 3.37.
was extracted with CH Cl . The organic layer was washed
2
2
0
0
00
with H O and saturated NaCl solution, dried over Na SO ,
2
3.1.11. 9,10-Dihydrodispiro[anthracene-9,2 -oxirane-3 ,2 -
3
2
4
,7
and concentrated under reduced pressure. The resultant resi-
due was puri®ed by silica gel column chromatography
tricyclo[3.3.1.1 ]decane] ꢀ3e). 99% yield, colorless crys-
tals, mp 235±2378C 6AcOEt). IRn 6KBr): 2913, 2850, 1ꢀ08,
2
1
MeCN
6
6
6
1
AcOEt±hexane, 1:ꢀ) to give the title compound 3a
333 mg, ꢀ4%) as colorless crystals, mp 227±2298C
AcOEt). IR n 6KBr): 2913, 2849, 159ꢀ, 149ꢀ, 14ꢀ4,
1447, 1351, 1147, 1097 cm . UV lmax
nm 61): 2ꢀ4
1
61000). H NMR 6CDCl
) d: 1.15 62H, br d, Jˆ12Hz), 1.ꢀ0
3
62H, br d, Jˆ12Hz), 1.ꢀ5±1.85 6ꢀH, m), 1.95 61H, br s),
2.14 62H, br d, Jˆ12 Hz), 3.92, 4.0ꢀ 62H, AB q, Jˆ1ꢀ Hz),
7.18±7.25 64H, m), 7.27±7.32 62H, m), 7.37±7.43, 64H, m).
2
1
MeCN
1
372, 12ꢀ7 cm . UV l
nm 61): 280 618000). H
max
NMR 6CDCl ) d: 1.08 62H, br d, Jˆ12Hz), 1.35±1.85 69H,
3
1
3
m), 1.95 61H, br s), 2.10 62H, br d, Jˆ12 Hz), 5.27 62H, s),
C NMR 6CDCl ) d : 2ꢀ.ꢀ, 2ꢀ.9, 30.9, 35.3, 3ꢀ.4, 3ꢀ.5,
3 C
124.9, 125.4, 12ꢀ.ꢀ, 12ꢀ.7, 135.8, 137.5. EI-MS m/z 6%):
ꢀ
.84 62H, d, Jˆ8 Hz), ꢀ.97 62H, t, Jˆ7 Hz), 7.126 2H , dd,
1
Jˆ8, 2Hz), 7.15±7.3265H, m), 7.3ꢀ 6 2H , dd, Jˆ7, 2Hz).
329 6M , 15). Anal. Calcd for C24
Found: C, 87.48; H, 7.35.
H
24O: C, 87.7ꢀ; H, 7.37.
1
3
C NMR 6CDCl ) d : 2ꢀ.ꢀ, 27.0, 30.0, 34.9, 3ꢀ.0, 3ꢀ.4,
3
C
5
1
0.3, ꢀꢀ.1, 9ꢀ.1, 112.7, 119.9, 122.0, 125.3, 12ꢀ.ꢀ, 127.0,
27.4, 128.ꢀ, 13ꢀ.7, 142.9, EI-MS m/z 6%): 420 6M 1H, 7).
1
0
0
00
3.1.12. Dispiro[9H-¯uorene-9,2 -oxirane-3 ,2 -tricyclo
3
,7
Anal. Calcd for C H NO: C, 85.88; H, ꢀ.97; N, 3.34.
3
Found: C, 85.85; H, ꢀ.98; N, 3.30.
[3.3.1.1 ] decane] ꢀ3f). 99% yield, colorless crystals, mp
133±1348C 6AcOEt). IR n 6KBr): 2913, 2850, 1ꢀ08, 1447,
0
29
2
351, 1147, 1097 cm . UV l
1
MeCN
1
214 630000). H NMR 6CDCl
nm 61): 278 612000),
max
1
Other oxiranes 3b±f were prepared according to the same
procedure.
3
) d: 1.13 62H, br d, Jˆ12Hz),
1.ꢀ0±2.20 68H, m), 2.2ꢀ 62H, br d, Jˆ12 Hz). 2.43 62H, br
s), 7.18±7.24 62H, m), 7.38 64H, t, Jˆ8 Hz), 7.73 62H, d,
1
3
0
0
-tricyclo[3.3.1.1 ]decane] ꢀ3b). 74% yield, colorless
3
2
.1.8. 10-Methyldispiro[acridine-9ꢀ10H),2 -oxirane-3 ,
3,7
Jˆ7 Hz). C NMR 6CDCl
) d : 2ꢀ.3, 2ꢀ.8, 32.0, 35.4, 3ꢀ.0,
3 C
00
3ꢀ.4, 120.1, 124.0, 12ꢀ.2, 128.4, 140.8, 141.9. EI-MS m/z
H22O: C, 87.8ꢀ; H,
1
crystals, mp 241±2428C 6AcOEt). IR n 6KBr): 2905,
2
2
6%): 315 6M , 41). Anal. Calcd for C23
7.05. Found: C, 87.72; H, 7.38.
2
1
850, 1595, 1470, 134ꢀ, 12ꢀ8 cm . UV l
MeCN
nm 61):
80 614000), 214 633000). H NMR 6CDCl ) d: 1.05 62H, br
max
1
3
d, Jˆ12 Hz), 1.35±1.80 69H, m), 1.94 61H, br s), 2.10 62H,
br d, Jˆ12Hz), 3.4ꢀ 63H, s), ꢀ.99 64H, t, Jˆ8 Hz), 7.25 62H,
3.2. Typical procedure for the measurement of
chemiluminescence of the oxiranes 3
1
3
d, Jˆ8 Hz), 7.34 62H, d, Jˆ9 Hz). C NMR 6CDCl ) d :
3
C
2
1
9
ꢀ.ꢀ, 27.0, 30.2, 33.2, 34.9, 3ꢀ.0, 3ꢀ.4, ꢀꢀ.3, 9ꢀ.1, 111.3,
19.8, 122.5, 125.1, 127.4, 144.1. EI-MS m/z 6%): 344 6M ,
Alkaline hydrogen peroxide 60.1 M H O in 0.1 M aqueous
2
2
1
NaOH solution, 0.10 ml) was added to a DMSO or dioxane
2
7
). Anal. Calcd for C H NO: C, 83.93; H, 7.34; N, 4.08.
25
solution of the oxirane 3 61.0£10 M, 0.10 ml). DMSO,
which can dissolve all the oxiranes 3a±f, was employed
to study the structural effect on the chemiluminescence
6Table 1). Dioxane was employed to investigate the effect
of the kind of acid used 6Figs. 2±ꢀ) because 3a in dioxane
showed the strongest light emission. After a certain period
of time 625 s for the addition of HCl and ꢀ0 s for the addition
of the other acids), an aqueous solution of the acid 60.2M,
0.10 ml) was added to the reaction mixture. Light emission
was immediately monitored for 120 s on a photon counter.
2
4
Found: C, 83.98; H, 7.31; N, 4.03.
0
0
00
3
.1.9. 10-Phenyldispiro[acridine-9ꢀ10H),2 -oxirane-3 ,2 -
3
,7
tricyclo[3.3.1.1 ]decane] ꢀ3c). ꢀ3% yield, colorless crys-
tals, mp 284±28ꢀ8C 6AcOEt). IR n 6KBr): 2987, 2851,
2
598, 1497, 1458, 1319, 128ꢀ cm . UV l
1
MeCN
1
2
1
nm 61):
max
1
87 614000). H NMR 6CDCl ) d: 1.19 62H, br d, Jˆ12Hz),
3
.40±1.85 69H, m), 1.95 61H, br s), 2.10 62H, br d,
Jˆ12Hz), ꢀ.44 6 2H , d, Jˆ8 Hz), ꢀ.97 62H, t, Jˆ7 Hz),
7
6
.07 62H, t, Jˆ8 Hz), 7.37 64H, d, Jˆ8 Hz), 7.50±7.70
3 C
1
3H, m). C NMR 6CDCl ) d : 2ꢀ.7, 27.0, 30.2, 34.9,
3
3
1
ꢀ.3, 3ꢀ.4, ꢀꢀ.0, 9ꢀ.1, 113.2, 119.9, 120.4, 125.2, 127.0,
28.4, 130.ꢀ, 131.1, 140.4, 144.0. EI-MS m/z 6%): 40ꢀ
Acknowledgements
1
6
M , 5). Anal. Calcd for C H NO: C, 85.89; H, ꢀ.71; N,
2
This work was supported by Grant-in-Aid for Scienti®c
Research 6B), No. 114704ꢀ9, from Japan Society for
Promotion of Science.
9
27
3
.45. Found: C, 85.98; H, ꢀ.81; N, 3.43.
0
0
00
3
.1.10. Ethyl dispiro[acridine-9ꢀ10H),2 oxirane-3 ,2 -
3
,7
tricyclo[3.3.1.1 ] decane]-10-acetate ꢀ3d). 72% yield,
colorless crystals, mp 2ꢀ3±2ꢀ58C 6AcOEt). IR n 6KBr):
References
2
1
912, 2849, 1753, 1598, 1499, 14ꢀ4, 13ꢀꢀ, 1189,
nm 61): 308 65000), 27ꢀ
2
101 cm . UV l
1
MeCN
max
1. 6a) Beck, S.; Koster, H. Anal. Chem. 1990, 62, 2258±2270.

K. Miyashita et al. / Tetrahedron 57ꢀ2001) 3361±3367
33ꢀ7
6
b). Mayer, A.; Neuenhofer, S. Angew. Chem., Int. Ed. Engl.
994, 33, 1044±1072.
Tetrahedron Lett. 1997, 38, 841±844. Imanishi, T.; Ueda,
Y.; Tainaka, R.; Kuni, N.; Minagawa, M.; Hoshino, N.;
Miyashita, K. Heterocycles 1998, 47, 828±838.
1
2
. For example: Schaap, A. P.; Handley, R. S.; Giri, B. P.
Tetrahedron Lett. 1987, 28, 935±938. Schaap, A. P.;
Sandison, M. D.; Handley, R. S. Tetrahedron Lett. 1987, 28,
ꢀ. A part of this work appeared in a preliminary communication:
Imanishi, T.; Ueda, Y.; Minagawa, K.; Hoshino, N.;
Miyashita, K. Tetrahedron Lett. 1997, 38, 39ꢀ7±3970.
7. Dictionary of Organic Compounds, Buckingham, J., Ed.; 5th
ed., Chapman & Hall: New York, 1982.
1
2
159±11ꢀ2. Adam, W.; Schulz, M. H. Chem. Ber. 1992, 125,
455±24ꢀ1. Matsumoto, M.; Kobayashi, H.; Matsubara, J.;
Watanabe, N.; Yamashita, S.; Oguma, D.; Kitano, Y.;
Ikawa, H. Tetrahedron Lett. 1996, 37, 397±400. Matsumoto,
M.; Watanabe, N.; Kobayashi, H.; Suganuma, H.; Matsubara,
J.; Kitano, Y.; Ikawa, H. Tetrahedron Lett. 1996, 37, 5939±
8. As an example dealing with the change in the chemilumines-
cent pro®le, Matsumoto and coworkers reported that the half-
life time of the light-emission is increased by employing
conformationally restricted spirocyclic dioxetanes and this is
likely attributable to the degree of conjugation of the aromatic
ring as an electron donor with the C±O bond of the dioxetane
ring: Matsumoto, M.; Watanabe, N.; Shiono, T.; Suganuma,
H.; Matsubra, J. Tetrahedron Lett. 1997, 38, 5825±5828.
9. Although formation of the dioxetane 8 from the anti-confor-
mation anti-7 could be possible as shown in Fig. 8, the effect
of the functional carboxylic acids would support the formation
of 8 from the syn-conformation syn-7. Participation of the
acridane nitrogen via hydrogen bonding with the functional
carboxylic acids in the anti-conformation anti-7 appears to be
negligible because of a considerably long distance between
the nitrogen and the hydroxy group.
5
942. Matsumoto, M.; Arai, N.; Watanabe, N. Tetrahedron
Lett. 1996, 37, 8535±8538. Matsumoto, M.; Watanabe, N.;
Kasuga, N. C.; Hamada, F.; Tadokoro, K. Tetrahedron Lett.
1
Arghavani, Z.; Schaap, A. P. J. Am. Chem. Soc. 1997, 119,
997, 38, 28ꢀ3±28ꢀꢀ. Akhavan-Tafti, H.; Eickholt, R. A.;
2
45±24ꢀ. Matsumoto, M.; Azami, M. Tetrahedron Lett. 1997,
8, 8947±8950. Jefford, C. W.; Deheza, M. F.; Wang, J. B.
3
Heterocycles 1997, 46, 451±4ꢀ2. Matsumoto, M.; Watanabe,
N.; Shiono, T.; Suganuma, H.; Matsubara, J. Tetrahedron Lett.
1
997, 38, 5825±5828. Matsumoto, M.; Watanabe, N.;
Kobayashi, H.; Azami, M.; Ikawa, H. Tetrahedron Lett.
997, 38, 411±414. Matsumoto, M.; Murakami, H.;
1
Watanabe, N. Chem. Commun. 1998, 2319±2320. Adam,
W.; Saha-Moeller, C. R.; Schambony, S. B. J. Am. Chem.
Soc. 1999, 121, 1834±1838. Jefford, C. W.; Deheza, M. F.
Heterocycles 1999, 50, 1025±1031. Nery, A. L. P.; Ropke,
S.; Catalani, L. H.; Baader, W. J. Tetrahedron Lett. 1999, 40,
2
443±244ꢀ. Watanabe, N.; Kobayashi, H.; Azami, M.;
Matsumoto, M. Tetrahedron 1999, 55, ꢀ831±ꢀ840. Watanabe,
N.; Suganuma, H.; Kobayashi, H.; Mutoh, H.; Katao, Y.;
Matsumoto, M. Tetrahedron 1999, 55, 4287±4298.
Matsumoto, M.; Hiroshima, T.; Chiba, S.; Isobe, R.;
Watanabe, N.; Kobayashi, H. Luminescence 1999, 14, 345±
Figure 8. Formation of dioxetane 8 from anti-7.
3
Luminescence 1999, 14, 341±344.
48. Matsumoto, M.; Kawahara, M.; Watanabe, N.
1
1
0. Lee, C.; Singer, L. A. J. Am. Chem. Soc. 1980, 102, 3823±
829.
3
3
4
. 6a) Sakanishi, K.; Nugroho, M. B.; Kato, Y.; Yamazaki, N.
Tetrahedron Lett. 1994, 35, 3559±35ꢀ2. 6b) Sakanishi, K.;
Kato, Y.; Mizukoshi, E.; Shimizu, K. Tetrahedron Lett.
1. Chemiluminescent spectrum for 3a showed a maximum
emission wavelength at 439 nm, while the ¯uorescent spec-
trum of 4a showed a maximum wavelength at 440 nm. This
experimental result supports our assumption that, in this
chemiluminescence of 3a, the excited state of 4a emits light
on going down to the ground state as expected.
1994, 35, 4789±4792.
. Schuster, G. B.; Turro, N. J.; Steinmetzer, H.-C.; Schaap, A. P.;
Faler, G.; Adam, W.; Liu, J. C. J. Am. Chem. Soc. 1975, 97,
7
2
110±7118. Adam, W.; Lechtken, P. Chem. Ber. 1976, 109,
8ꢀ2±2870. H oÈ hne, G.; Schmidt, A. H.; Lechtken, P.
12. 6a) Galy, J. P.; Elguero, J.; Vincent, E. J.; Galy, A. M.; Barbe,
J. Synthesis 1979, 944±94ꢀ. 6b) Nishi, H.; Kohno, H.; Kano, T.
Bull. Chem. Soc. Jpn 1981, 54, 1897±1898. 6c) Mitteilung, V.
Ber 1907, 40, 2448±2452. 6d) Postescu, I. D.; Cs a v a ssy, G.
J. Prakt. Chem. 1977, 319, 347±352. 6e) Miosga, N.; R oÈ mer,
W.; Letsch, G. Pharmazie 1985, 40, 800±801.
Tetrahedron Lett. 1976, 3587±3590. Encarnacion, L. A. A.;
Zinner, K. Chem. Ber. 1983, 116, 839±84ꢀ.
5
. For our previous work on dioxetane derivatives: Imanishi, T.;
Ueda, Y.; Tainaka, R.; Miyashita, K.; Hoshino, N.