Synthesis of bicyclic dioxetanes bearing a 4-(benzimidazol-2-yl)-3- hydroxyphenyl group and their base-induced chemiluminescent decomposition in an aprotic medium and in an aqueous medium

Article abstract of DOI:10.3987/COM-12-12602

Bicyclic dioxetane, 5-tert-butyl-4,4-dimethyl-2,6,7-trioxabicyclo[3.2.0] heptane, bearing a 4-(benzimidazol-2-yl)-3-hydroxyphenyl group at the 1-position and its N-substituted benzimidazolyl-analogs were synthesized. N-Methylbenzimidazolyl-analog and N-phenylbenzimidazolyl-analog were found to undergo charge-transfer-induced decomposition(CTID) to effectively give light in both TBAF/MeCN and in NaOH/H₂O. The CTID of N-(4-carboxybutyl) benzimidazolyl-analog gave also effectively light both in MeCN and in H2O. On the other hand, chemiluminescent CTID of the unsubstituted benzimidazolyl-analog changed depending on the base used: TBAF/MeCN induced weak emission of yellow light due to a dianion of the dioxetane, while TMG(tetramethylguanidine)/MeCN induced strong emission of blue light due to a monoanion of the dioxetane.

Full text of DOI:10.3987/COM-12-12602

HETEROCYCLES, Vol. 87, No. 1, 2013
65
HETEROCYCLES, Vol. 87, No. 1, 2013, pp. 65 - 78. © 2013 The Japan Institute of Heterocyclic Chemistry
Received, 9th October, 2012, Accepted, 31st October, 2012, Published online, 8th November, 2012
DOI: 10.3987/COM-12-12602
SYNTHESIS
OF
BICYCLIC
DIOXETANES
BEARING
A
4-(BENZIMIDAZOL-2-YL)-3-HYDROXYPHENYL GROUP AND THEIR
BASE-INDUCED CHEMILUMINESCENT DECOMPOSITION IN AN
APROTIC MEDIUM AND IN AN AQUEOUS MEDIUM
Hiromasa Hagiwara, Nobuko Watanabe, Hisako K. Ijuin, Masashi Yamada,1
and Masakatsu Matsumoto*
*Department of Chemistry, Kanagawa University, Tsuchiya, Hiratsuka,
1
Kanagawa 259-1293, Japan Tosoh AIA, Inc. Iwase, Koshi-machi, Toyama
931-8510, Japan E-mail: matsumo-chem@kanagawa-u.ac.jp
Abstract
–
Bicyclic
dioxetane,
5-tert-butyl-4,4-dimethyl-2,6,7-
trioxabicyclo[3.2.0]heptane, bearing a 4-(benzimidazol-2-yl)-3-hydroxyphenyl
group at the 1-position and its N-substituted benzimidazolyl-analogs were
synthesized. N-Methylbenzimidazolyl-analog and N-phenylbenzimidazolyl-analog
were found to undergo charge-transfer-induced decomposition (CTID) to
effectively give light in both TBAF/MeCN and in NaOH/H2O. The CTID of
N-(-carboxybutyl)benzimidazolyl-analog gave also effectively light both in
MeCN and in H2O. On the other hand, chemiluminescent CTID of the
unsubstituted benzimidazolyl-analog changed depending on the base used:
TBAF/MeCN induced weak emission of yellow light due to a dianion of the
dioxetane, while TMG(tetramethylguanidine)/MeCN induced strong emission of
blue light due to a monoanion of the dioxetane.
INTRODUCTION
Upon treatment with a base, a hydroxyphenyl-substituted dioxetane is deprotonated to give an unstable
oxidophenyl-substituted dioxetane which rapidly decomposes with an accompanying emission of light by
intramolecular charge-transfer-induced decomposition (CTID) mechanism. This phenomenon has
received considerable attention from the viewpoints of application to clinical and biological analysis as
well as of mechanistic interest related to bioluminescence and chemiluminescence.1−7 One of such
CTID-active dioxetanes is bicyclic compound 1 bearing a 4-(benzothiazol-2-yl)-3-hydroxyphenyl group,
which effectively emits light in an aqueous system as well as in an aprotic polar solvent.8 Furthermore,

66
HETEROCYCLES, Vol. 87, No. 1, 2013
dioxetane 1 has very recently been found to undergo solvent-promoted decomposition, which is an
entropy-controlled reaction leading to effective chemiluminescence.9
O
R
OH
S
N
N
N
N
N
O O
O O
O O
HO
HO
HO
t-Bu
t-Bu
t-Bu
O
O
O
2a: R = H
2b: R = Me
2c: R = Ph
2d
1
Figure 1. Dioxetanes bearing a 3-hydroxyphenyl group substituted with a 4-(benzothizol-2-yl) 1 or
4-(benzimidazol-2-yl) group 2a−d
These facts prompted us to realize bicyclic dioxetanes 2 bearing a 4-(benzimidazol-2-
yl)-3-hydroxyphenyl group with expectation that the skeleton of 2 could be developed to novel
chemiluminescence substrates bearing various auxiliaries, since a saturated nitrogen of benzimidazolyl
group could be easily functionalized or tethered, differently from benzothiazolyl or benzoxazolyl group.
Thus, we basically investigated here whether or not dioxetanes 2 showed effective chemiluminescence in
an aqueous medium as well as in an aprotic medium. Dioxetanes investigated here were parent 2a
bearing a 4-(benzimidazol-2-yl)-3-hydroxyphenyl group and its N-methylbenzimidazolyl- 2b,
N-phenylbenzimidazolyl- 2c and N-(4-carboxybutyl)benzimidazolyl-analog 2d (Figure 1).
RESULTS AND DISCUSSION
Synthesis of bicyclic dioxetanes bearing a 4-(benzimidazol-2-yl)-3-hydroxyphenyl group
All of the dioxetanes 2a−d investigated here were prepared by singlet oxygenation of the corresponding
5-[4-(benzimidazol-2-yl)-3-hydroxyphenyl]-4-tert-butyl-3,3-dimethyl-2,3-dihydrofurans 3a−d.
These
precursors were synthesized through several steps starting from 4-tert-butyl-5-(4-carboxy-3-
methoxyphenyl)-3,3-dimethyl-2,3-dihydrofuran (5), which was synthesized from 5-(4-bromo-3-
methoxyphenyl)-4-tert-butyl-3,3-dimethyl-2,3-dihydrofuran (4),10 as illustrated in Scheme 1.
The initial step was condensation of carboxylic acid 5 with benzene-1,2-diamines 6a−c, which smoothly
proceeded by using triphenylphosphonium anhydride trifluoromethanesulfonate (POP)11 in CH2Cl2 at
room temperature to give the corresponding benzimidazoles 7a−c. Nucleophilic substitution of
benzimidazole 7a with ethyl 5-bromopentanoate gave ester 8.
These 4-benzimidazolyl-
3-methoxyphenyl-substituted dihydrofurans 7a−c and 8 were demethylated effectively with sodium
methylthiolate to give the desired precursors 3a−d: for the case of 8, saponification of the ester function

HETEROCYCLES, Vol. 87, No. 1, 2013
67
also proceeded. All of dihydrofurans 3a−d were individually irradiated with Na-lamp in the presence of
catalytic amount of tetraphenylporphin (TPP) in acetone or CH2Cl2 under O2 atmosphere at 0 °C to
selectively give the corresponding dioxetanes 2a−d. The structures of dioxetanes 2a−d were determined
by 1H NMR, 13C NMR, IR, MS and HRMass spectral analyses.
R
N
O
Br
N
HO
MeO
3)
1), 2)
NHR
MeO
MeO
t-Bu
t-Bu
t-Bu
NH
2
O
O
O
6a-c
7a-c
5
4
4)
O
R
N
OEt
N
N
5)
N
4)
7a
HO
t-Bu
MeO
t-Bu
O
O
3a-d
8
a: R = H
b: R = Me
c: R = Ph
Reagents: 1) BuLi/THF, 2) CO2, dry ice, 3) POP/CH2Cl2, 4) MeSNa/DMF/,
d: R = (CH2)4CO2H
5) Br(CH2)4CO2Et/NaH/DMF
Scheme 1. Synthetic pathway of dihydrofurans 3a−d bearing a 4-(benzimidazol-2-yl)-3-hydroxyphenyl
group
Base-induced chemiluminescent decomposition of dioxetanes bearing a 4-(benzimidazol-2-yl)-
3-hydroxyphenyl group
When a solution of dioxetane 2a in MeCN was added to a solution of tetrabutylammonium fluoride
(TBAF, large excess) in MeCN at 45 ºC, 2a decomposed according to the pseudo-first order kinetics
independent of the TBAF concentration to emit yellow light, the spectrum of which is shown in Figure
2(A). The chemiluminescence properties of 2a were as follows: maximum wavelength maxCL = 510 nm,
CTID
chemiluminescence efficiency CL = 0.065,12,13 rate of CTID kCTID = 4.6 x 10−3 s-1, and half-life t1/2
=
150 s (Table 1). On similar treatment with TBAF, 2b and 2c showed bright chemiluminescence, the
properties of which are shown in Table 1 (Figure 2(A)). We can see from Table 1 that 2b and 2c
emitted light as effectively as benzothiazolyl-analog 1, while, in contrast, parent 2a gave light in poor
yield, and the maxCL was considerably longer for 2a than those for 2b and 2c.

68
HETEROCYCLES, Vol. 87, No. 1, 2013
Next, we carried out CTID of dioxetanes 2ac in an aqueous system. When dioxetanes 2ac were
individually treated with 0.1 M NaOH aqueous solution at 45 ºC, they decomposed with the accompanying
chemiluminescence. Their chemiluminescence properties and spectra are summarized in Table 1 and
Figure 2(B), respectively. Table 1 shows that all of three dioxetanes 2ac emitted light in high yields,
which were >1000 times higher than that for simple bicyclic dioxetane, 5-tert-butyl-1-(3-hydroxyphenyl)-
4,4-dimethyl-2,6,7-trioxabicyclo[3.2.0]heptane (9),14 though they were somewhat lower than that for 1.
If we compare here features of CTID for 2ac in a NaOH/H2O system to those in a TBAF/MeCN, we can
CL
see that only parent dioxetane 2a showed the noticeable differences in max and in CL between these
CL
two systems. The max for 2a was 33 nm shorter in an aqueous system than in an MeCN system,
though those for 2b and 2c were not so much different between in these two systems.
Chemiluminescence efficiency for 2a was unexpectedly higher in the aqueous system than in the MeCN
system, while those for 2b and 2c somewhat decreased in an aqueous system. Notably, 2a was the first
example that a CTID-active dioxetane emitted light more effectively in an aqueous system than in an
aprotic polar solvent system.
Figure 2. Chemiluminescence spectra of dioxetanes 2a−d in TBAF/MeCN (A) and in NaOH/H2O (B)
and fluorescence spectra of keto esters 10a−d in TBAF/MeCN (C) and in NaOH/H2O (D)
The freshly spent reaction mixture for 2ac in both base systems effectively gave the corresponding keto

HETEROCYCLES, Vol. 87, No. 1, 2013
69
ester 10ac after careful neutralization. Authentic oxido anions 11ac generated by dissolving 10ac in
NaOH/H2O gave fluorescences, the spectra of which coincided with the corresponding
chemiluminescence spectra of 2ac (Figure 2(D)). The results suggest that 11ac were undoubtedly
emitters for CTID of the corresponding dioxetanes 2ac in a NaOH/H2O system (Scheme 2). On the
other hand, in a TBAF/MeCN system, fluorescence spectrum of 11a generated from 10a did not coincide
with chemiluminescence spectrum from 2a, though fluorescence spectra of authentic 11b and 11c
coincided with the corresponding chemiluminescence spectra of 2b and 2c (Figure 2(C)).
R
R
N
N
N
N
TBAF/MeCN
or NaOH/H2O
CTID
2a-c
O
O
O O
YO
O
t-Bu
t-Bu
O
O
Light
12a-c
11a-c: Y =
10a-c: Y = H
H
R = H
TBAF
N
N
N
N
CTID
O O
O
O
O O
HO
t-Bu
O
O
t-Bu
t-Bu
O
O
O
Light
14a
9
13a
Scheme 2. Base-Induced decomposition of dioxetanes 2a−c
We carried out several experiments to understand the discrepancy between fluorescence spectrum of 11a
and chemiluminescence spectrum of 2a in a TBAF/MeCN. Prominent difference in the structure
between 2a and 2b or 2c was that only benzimidazolyl group in 2a possesses a weakly acidic NH. This
structural difference suggested that 2a would decompose in different manner depending on a base system.
Thus, we attempted to use tetramethylguanidine (TMG, pKa = 13.6) as a base far weaker than TBAF
(pKa >> 15) though strong enough for CTID of 2a in MeCN. When a solution of 2a in MeCN was
added to a solution of MeCN including a large excess of TMG instead of TBAF at 45 °C, 2a showed
chemiluminescence with maxCL = 471 nm, CL = 0.22, kCTID = 1.9 x 10−4 and t1/2 = 3700 s.
This maxCL was 39 nm shorter than that in a TBAF/MeCN, and coincided with maxfl of fluorescence from

70
HETEROCYCLES, Vol. 87, No. 1, 2013
authentic 11a in TBAF/MeCN as well as in TMG/MeCN (Figure 2(C)). We can understand from Table
1 that CL of 2a in a TMG/MeCN system increased more than 3 times from that in a TBAF/MeCN
system, and was same as that for 2b in a TBAF/MeCN. These results suggested that a strong base
TBAF produced dianion 14a of keto ester in the excited state through dianion 13a of dioxetane 2a,
whereas TMG could abstract only a phenolic proton of 2a to produce monoanion of dioxetane 12a which
decomposed into monoanion 11a in the excited state (Scheme 2).
Table 1. Base-induced chemiluminescent decomposition of bicyclic dioxetanes 2a−2d bearing a
4-(benzimidazol-2-yl)-3-hydroxyphenyl moiety in TBAF/MeCN and in NaOH/H2Oa)
Dioxetane
TBAF/MeCN
NaOH/H2O
CL b)
maxCL / nm
CL b)
0.065
0.22
0.23
0.20
0.28
0.11
0.22
t1/2 / s
150
90
maxCL / nm
477
t1/2 / s
246
361
164
396
280
810
-----
2a
2b
2c
510
483
492
483
492
467
471
0.070
480
0.024
36
485
0.086
2d
1
9c)
2ad)
63
483
0.017
1600
25
492
0.12
1.1 x 10−5
467
3700
-----
-----
a) Reactions were carried out at 45 °C. b) Chemiluminescence efficiencies were based
on the reported value for 3-(3-tert-butyldimethylsiloxyphenyl)-3-methoxy-4-
(2’-spiroadamantane)-1,2-dioxetane (CL = 0.29).13 c) ref. 14 d) TMG was used as a
base instead of TBAF.
As described above, dioxetane 2b bearing a 3-hydroxy-4-(N-methylbenzimidazol-2-yl)phenyl group
underwent CTID to effectively give light in both TBAF/MeCN and NaOH/H2O systems. Thus, we
investigated whether or not the substitution with -functionalized alkyl group instead of N-methyl in 2b
could keep up chemiluminescence properties, especially high CL, for base-induced decomposition. As
a representative of -functionalized alkyl group, we selected 4-carboxybutyl group, which could tether
various auxiliaries or pendants (Figure 1).
Dioxetane bearing an 4-[N-(4-carboxybutyl)-
benzimidazol-2-yl]-3-hydroxyphenyl group 2d decomposed to effectively emit light in both
TBAF/MeCN and NaOH/H2O systems (Figure 2). The results summarized in Table 1 show that
chemiluminescence properties for 2d were practically similar to those for 2b.
CONCLUSION
Bicyclic dioxetane bearing a 4-(benzimidazol-2-yl)-3-hydroxyphenyl group 2a and its N-substituted
benzimidazolyl-analogs 2b−2d were synthesized.
N-Methylbenzimidazolyl-analog 2b and
N-phenylbenzimidazolyl-analog 2c were found to undergo CTID to effectively give light in both

HETEROCYCLES, Vol. 87, No. 1, 2013
71
CL
TBAF/MeCN and in NaOH/H2O. On the other hand, CL, max and kCTID for CTID of unsubstituted
benzimidazolyl-analog 2a changed depending on the base used: especially CL in TBAF/MeCN system
was quite low and was only <1/3 of CL in TMG/MeCN system. CTID of N-(-carboxybutyl)-
benzimidazolyl-analog 2d gave also effectively light both in MeCN and in H2O. The results presented
here show that design of new CTID-dioxetanes tethering various auxiliaries through an N-spacer can
become possible.
EXPERIMENTAL
General
1
Melting points were uncorrected. IR spectra were taken on a FT/IR infrared spectrometer. H and 13C
NMR spectra were recorded on a 400 MHz and 500 MHz spectrometers. Mass spectra were obtained by
using a double-focusing mass spectrometer and an ESI-TOF mass spectrometer. Column chromatography
was carried out using SiO2.
Synthesis of 5-(4-carboxy-3-methoxyphenyl)-4-tert-butyl-3,3-dimethyl-2,3-dihydrofuran (5): BuLi
(4.30 mL, 1.62 M in hexane, 6.97 mmol) was added to a solution of 5-(4-bromo-3-methoxyphenyl)-
4-tert-butyl-3,3-dimethyl-2,3-dihydrofuran (4) (2.22 g, 6.56 mmol) in dry THF (20 mL) under a nitrogen
atmosphere at -78 °C. After stirring for 30 min, dry ice was added to the solution and the reaction
mixture was warmed slowly to room temperature. The reaction mixture was poured into 1 M HCl and
extracted with AcOEt. The organic layer was washed twice with sat. aq. NaCl, dried over anhydrous
MgSO4, and concentrated in vacuo. The residue was chromatographed on silica gel and eluted with
AcOEt−hexane (1:9~1:1) to give 5 (1.73 g, 5.69 mmol, 87%). 5: colorless needles, mp 103.0−10.4.0 °C
(from AcOEt−hexane). 1H NMR (400 MHz, CDCl3): H 1.07 (s, 9H), 1.35 (s, 6H), 3.90 (s, 2H), 4.09 (s,
3H), 6.98 (d, J = 1.1 Hz, 1H), 7.11 (dd, J = 7.9 and 1.1 Hz, 1H), 8.15 (d, J = 7.9 Hz, 1H), 10.60 (br s, 1H)
ppm. 13C NMR (125 MHz, CDCl3): C 27.3, 32.5, 32.5, 47.4, 56.8, 83.4, 113.2, 117.1, 124.1, 127.2, 133.4,
143.4, 148.0, 157.5, 165.0 ppm. IR (KBr): 3448, 2956, 1687, 1604, 1561 cm−1. Mass (m/z, %): 304 (M+,
22), 289 (100), 245 (22), 215 (30), 179 (29), 52 (21). HRMS (ESI): 327.1554 calcd for C18H24O4Na
[M+Na+] 327.1572.
Synthesis of 5-[4-(benzimidazol-2-yl)-3-methoxyphenyl]-4-tert-butyl-3,3-dimethyl-2,3-dihydrofuran
(7a): Typical procedure. Triphenylphosphonium anhydride trifluoromethanesulfonate (POP) was
prepared by adding trifluoromethanesulfonic anhydride (2.19 mL, 13.0 mmol) to a solution of
triphenylphosphine oxide (7.26 g, 26.1 mmol) in dry CH2Cl2 (15 mL) under a nitrogen atmosphere at
room temperature and stirring for 20 min. To the POP solution, 5-(4-carboxy-3-methoxyphenyl)-
4-tert-butyl-3,3-dimethyl-2,3-dihydrofuran (5) (1.00 g, 3.29 mmol) and 1,2-phenylenediamine (353 mg,
3.26 mmol) in dry CH2Cl2 (10 mL) were added and stirred at room temperature over night. The reaction
mixture was poured into sat. aq. NaHCO3 and extracted with AcOEt. The organic layer was washed twice

72
HETEROCYCLES, Vol. 87, No. 1, 2013
with sat. aq. NaCl, dried over anhydrous MgSO4, and concentrated in vacuo. The residue was
chromatographed on silica gel and eluted with AcOEt−hexane (1:2) to give 7a (753 mg, 2.00 mmol, 62%)
as a pale yellow solid. 7a: colorless needles, mp 233.5−234.0 °C (from AcOEt). 1H NMR (400 MHz,
CDCl3): H 1.09 (s, 9H), 1.36 (s, 6H), 3.92 (s, 2H), 4.11 (s, 3H), 7.01 (s with fine coupling, 1H), 7.12 (d
with fine coupling, J = 7.9 Hz, 1H), 7.23−7.30 (m, 2H), 7.42−7.58 (m, 1H), 7.72−7.90 (m, 1H), 8.56 (d, J
= 7.9 Hz, 1H), 10.60 (br s, 1H) ppm. 13C NMR (125 MHz, DMSO-d6): C 27.3, 32.3, 32.5, 47.0, 56.1,
82.5, 112.2, 113.4, 118.1, 118.7, 121.8, 122.4, 122.8, 125.8, 129.5, 134.9, 139.0, 142.9, 148.7, 149.1,
156.3 ppm. IR (KBr): 3435, 3056, 2962, 2870, 1646, 1611, 1570 cm−1. Mass (m/z, %): 377 (M++1,
13), 376 (M+, 43), 362 (28), 361 (100), 305 (30), 251 (13). HRMS (ESI): 377.2206 calcd for C24H29N2O2
[M+H+] 377.2229. Anal. Calcd for C24H28N2O2: C, 76.56; H, 7.50; N, 7.44. Found: C, 76.32; H, 7.69; N,
7.42.
4-tert-Butyl-5-[3-methoxy-4-(N-methylbenzimidazol-2-yl)phenyl]-3,3-dimethyl-2,3-dihydrofuran
1
(7b): 79% yield. Colorless plates, mp 158.0–158.5 °C (from CH2Cl2–hexane). H NMR (400 MHz,
CDCl3): H 1.10 (s, 9H), 1.37 (s, 6H), 3.64 (s, 3H), 3.83 (s, 3H), 3.93 (s, 2H), 6.96 (d, J = 1.2 Hz, 1H),
7.07 (dd, J = 7.6 and 1.2 Hz, 1H), 7.26−7.35 (m, 2H), 7.38−7.41 (m, 1H), 7.55 (d, J = 7.6 Hz, 1H),
7.80−7.83 (m, 1H) ppm. 13C NMR (125 MHz, CDCl3): C 27.3, 30.8, 32.4, 32.5, 47.3, 55.6, 83.2, 109.3,
112.5, 119.4, 119.7, 121.9, 122.4, 122.7, 126.4, 131.8, 136.0, 139.6, 143.1, 149.1, 151.7, 157.0 ppm. IR
(KBr): 3049, 2958, 2871, 1655, 1609, 1563 cm−1. Mass (m/z, %): 391 (M++1, 16), 390 (M+, 53), 376 (29),
375 (100), 319 (35), 265 (8). HRMS (ESI) : 391.2401 calcd for C25H31N2O2 [M+H+] 391.2386. Anal.
Calcd for C25H30N2O2: C, 76.89; H, 7.74; N, 7.17. Found: C, 76.98; H, 7.93; N, 7.19.
4-tert-Butyl-5-[3-methoxy-4-(N-phenylbenzimidazol-2-yl)phenyl]-3,3-dimethyl-2,3-dihydrofuran
(7c): 56% yield. Colorless amorphous solid. 1H NMR (400 MHz, CDCl3): H 1.04 (s, 9H), 1.33 (s, 6H),
3.33 (s, 3H), 3.89 (s, 2H), 6.66 (d, J = 1.2 Hz, 1H), 7.01 (dd, J = 7.6 and 1.2 Hz, 1H), 7.20−7.40 (m, 8H),
7.63 (d, J = 7.6 Hz, 1H), 7.88 (d, J = 7.6 Hz, 1H) ppm. 13C NMR (125 MHz, CDCl3): C 27.3, 32.4,
32.4, 47.2, 54.7, 83.2, 110.2, 112.4, 119.7, 119.9, 122.5, 123.1, 125.8, 126.3, 127,5, 129.0, 131.6, 136.0,
137.1, 139.3, 143.1, 149.1, 150.9, 156.4 ppm. IR (KBr): 3057, 2956, 2865, 1652, 1604, 1565, 1499 cm−1
.
Mass (m/z, %): 453 (M++1, 24), 452 (M+, 70), 438 (34), 437 (100), 381 (29), 327 (13), 298 (12). HRMS
(ESI): 453.2520 calcd for C30H33N2O2 [M+H+] 453.2542.
Synthesis of 4-tert-butyl-5-{4-[N-(4-ethoxycarbonylbutyl)benzimidazol-2-yl]-3-methoxyphenyl}-
3,3-dimethyl-2,3-dihydrofuran
(8):
4-tert-Butyl-5-[4-(benzimidazol-2-yl)-3-methoxyphenyl]-3,3-
dimethyl-2,3-dihydrofuran (7a) (500 mg, 1.33 mmol) was added to a suspension of NaH (60% in oil, 70.2
mg, 1.76 mmol) in dry DMF (10 mL) under a nitrogen atmosphere at room temperature. After stirring for
30 min, ethyl 5-bromopentanoate (0.32 mL, 2.0 mmol) was added to the solution at room temperature and
stirred for 2 days. The reaction mixture was poured into sat. aq. NH4Cl and extracted with AcOEt. The
organic layer was washed twice with sat. aq. NaCl, dried over anhydrous MgSO4, and concentrated in
vacuo. The residue was chromatographed on silica gel and eluted with AcOEt−hexane (1:1) to give 8

HETEROCYCLES, Vol. 87, No. 1, 2013
73
(666 mg, 1.32 mmol, 99%). 8: Yellow oil. 1H NMR (400 MHz, CDCl3): H 1.09 (s, 9H), 1.21 (t, J = 7.1
Hz, 3H), 1.37 (s, 6H), 1.42−1.52 (m, 2H), 1.69−1.79 (m, 2H), 2.16 (t, J = 7.3 Hz, 2H), 3.81 (s, 3H), 3.93
(s, 2H), 4.01−4.11 (m, 4H), 6.96 (s, 1H), 7.06 (dd, J = 7.6 and 1.2 Hz, 1H), 7.23−7.33 (m, 2H), 7.38−7.43
13
(m, 1H), 7.47 (d, J = 7.6 Hz, 1H), 7.78−7.84 (m, 1H) ppm. C NMR (125 MHz, CDCl3): C 14.1, 22.0,
27.3, 28.7, 32.4, 32.5, 33.6, 44.1, 47.3, 55.6, 60.3, 83.2, 109.8, 112.6, 119.7, 120.0, 121.9, 122.4, 122.7,
126.5, 131.7, 135.0, 139.5, 143.3, 149.0, 151.2, 156.9, 172.8 ppm. IR (liquid film): 3055, 2957, 2868,
1732, 1651, 1609, 1563 cm−1. Mass (m/z, %): 505 (M++1, 23), 504 (M+, 60), 490 (37), 489 (100), 459
(11). HRMS (ESI): 505.3039 calcd for C31H41N2O4 [M+H+] 505.3066.
Synthesis of 5-[4-(benzimidazol-2-yl)-4-tert-butyl-3-hydroxyphenyl]-3,3-dimethyl-2,3-dihydrofuran
(3a): Typical procedure. MeSNa (95%, 120 mg, 1.63 mmol) was added to a solution of 7a (210 mg, 0.56
mmol) in dry DMF (5 mL) under a nitrogen atmosphere at room temperature and stirred for 30 min at
140 °C. The reaction mixture was poured into 1 M aq. HCl and sat. aq. NaCl, and extracted with AcOEt.
The organic layer was washed twice with sat. aq. NaCl, dried over anhydrous MgSO4, and concentrated
in vacuo. The residue was chromatographed on silica gel and eluted with AcOEt−hexane (1:4) to give 3a
(200 mg, 0.552 mmol, 99%) as a pale yellow solid. 3a: Colorless needles, mp 284.5−285.0 °C (from
AcOEt). 1H NMR (400 MHz, CDCl3): H 1.09 (s, 9H), 1.35 (s, 6H), 3.90 (s, 2H), 6.91 (dd, J = 8.0 and
1.5 Hz, 1H), 7.08 (d, J = 1.5 Hz, 1H), 7.28−7.34 (m, 2H), 7.46−7.53 (m, 1H), 7.52 (d, J = 8.0 Hz, 1H),
7.71−7.78 (m, 1H), 9.45 (br s, 1H), 13.09 (br s, 1H) ppm. 13C NMR (125 MHz, DMSO-d6): C 27.2, 32.3,
32.4, 47.0, 82.5, 111.7 (br), 112.6, 118.1 (br), 118.5, 121.0, 122.7 (br), 123.4 (br), 125.6, 126.0, 133.4 (br),
139.5, 141.1 (br), 149.0, 151.5, 157.5 ppm. IR (KBr): 3302, 2958, 2868, 2630, 1630, 1580 cm−1. Mass
(m/z, %): 363 (M++1, 11), 362 (M+, 39), 348 (27), 347 (100), 291 (38). HRMS (ESI): 363.2043 calcd
for C23H27N2O2 [M+H+] 363.2073. Anal. Calcd for C23H26N2O2: C, 76.21; H, 7.23; N, 7.73. Found: C,
76.47; H, 7.43; N, 7.72.
4-tert-Butyl-5-[3-hydroxy-4-(N-methylbenzimidazol-2-yl)phenyl]-3,3-dimethyl-2,3-dihydrofuran
(3b): 97% yield. Colorless columns, mp 136.0−137.0 °C (from AcOEt). 1H NMR (400 MHz, CDCl3):
H 1.11 (s, 9H), 1.35 (s, 6H), 3.90 (s, 2H), 4.07 (s, 3H), 6.93 (dd, J = 8.1 and 1.7 Hz, 1H), 7.13 (d, J = 1.7,
1H), 7.31−7.39 (m, 2H), 7.41−7.44 (m, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.75−7.78 (m, 1H), 12.92 (br s, 1H)
ppm. 13C NMR (125 MHz, CDCl3): C 27.3, 32.5, 32.5, 33.0, 47.3, 83.2, 109.5, 112.7, 118.8, 119.6,
120.2, 123.0, 123.3, 126.1, 126.5, 135.6, 139.6, 140.3, 149.0, 151.4, 158.6 ppm. IR (KBr): 3417, 2956,
2867, 1624, 1566, 1466 cm-1. Mass (m/z, %): 377 (M++1, 14), 376 (M+, 48), 362 (28), 361 (100), 305
(40). HRMS (ESI): 377.2212 calcd for C24H29N2O2 [M+H+] 377.2229 Anal. Calcd for C24H28N2O2: C,
76.56; H, 7.50; N, 7.44. Found: C, 76.52; H, 7.68; N, 7.46.
4-tert-Butyl-5-[3-hydroxy-4-(N-phenylbenzimidazol-2-yl)phenyl]-3,3-dimethyl-2,3-dihydrofuran
(3c): 82% yield. Pale yellow plates, mp 180.5-181.5 °C (from CH2Cl2). 1H NMR (400 MHz, CDCl3): H
1.05 (s, 9H), 1.30 (s, 6H), 3.83 (s, 2H), 6.49 (dd, J = 8.3 and 1.7 Hz, 1H), 6.79 (d, J = 8.3 Hz, 1H), 7.06 (d,
J = 1.7 Hz, 1H), 7.08 (d, J = 8.1 Hz, 1H), 7.23−7.29 (m, 1H), 7.32−7.42 (m, 3H), 7.56−7.63 (m, 3H), 7.80

74
HETEROCYCLES, Vol. 87, No. 1, 2013
(d, J = 8.1 Hz, 1H), 13.48 (br s, 1H) ppm. 13C NMR (125 MHz, CDCl3): C 27.2, 32.4, 32.4, 47.2, 83.1,
110.3, 111.9, 118.6, 119.5, 119.7, 123.4, 123.8, 126.0, 126.7, 127.9, 129.5, 130.3, 136.5, 137.1, 139.4,
140.0, 149.0, 150.6, 159.1 ppm. IR (KBr): 3431, 3065, 2955, 2867, 1623, 1596, 1565 cm−1. Mass
(m/z, %): 439 (M++1, 20), 438 (M+, 60), 424 (33), 423 (100), 381 (13), 368 (11), 367 (40), 285 (12).
HRMS (ESI): 439.2363 calcd for C29H31N2O2 [M+H+] 439.2386.
4-tert-Butyl-5-{4-[N-(4-carboxybutyl)benzimidazol-2-yl]-3-hydroxyphenyl}-3,3-dimethyl-2,3-dihydro-
furan (3d): 89% yield. Pale yellow columns, mp 174.0−175.0 °C (from CH2Cl2−hexane). 1H NMR (400
MHz, CDCl3): H 1.11 (s, 9H), 1.35 (s, 6H), 1.73−1.82 (m, 2H), 1.99−2.09 (m, 2H), 2.44 (t, J = 7.1 Hz,
2H), 3.90 (s, 2H), 4.39−4.48 (m, 2H), 6.94 (dd, J = 8.1 and 1.7 Hz, 1H), 7.13 (d, J = 1.7 Hz, 1H),
7.30−7.38 (m, 2H), 7.40−7.45 (m, 1H), 7.58 (d, J = 8.1 Hz, 1H), 7.73−7.80 (m, 1H) ppm. 13C NMR
(125 MHz, CDCl3): C 21.8, 27.3, 29.1, 32.5, 32.5, 33.2, 45.2, 47.2, 83.2, 109.7, 112.8, 118.9, 119.9,
120.5, 123.1, 123.4, 125.9, 126.3, 134.9, 139.6, 140.3, 148.8, 150.7, 158.4, 178.4 ppm. IR (KBr): 3386,
3061, 2955, 2865, 1723, 1654, 1618, 1558 cm−1. Mass (m/z, %): 463 (M++1, 25), 462 (M+, 77), 448
(36), 447 (100), 445 (21), 403 (17), 391 (30), 389 (20), 347 (32), 291 (18), 57 (18). HRMS (ESI):
463.2591 calcd for C28H35N2O4 [M+H+] 463.2597.
Synthesis
of
1-[4-(benzimidazol-2-yl)-3-hydroxyphenyl]-5-tert-butyl-4,4-dimethyl-2,6,7-trioxa-
bicyclo[3.2.0]heptane (2a): Typical procedure. A solution of 3a (164 mg, 0.45 mmol) and
tetraphenylporphine (TPP) (2.0 mg) in acetone (10 mL) was irradiated externally with 940W Na lamp
under an oxygen atmosphere for 1.5 h at 0 °C. The reaction mixture was concentrated in vacuo. The
photolysate was rinsed with CH2Cl2 to give dioxetane 2a (139 mg, 78%). 2a: Pale yellow granules, mp
284.0−285.0 °C (dec.) (from THF−hexane). 1H NMR (400 MHz, DMSO-d6): H 0.99 (s, 9H), 1.10 (s,
3H), 1.38 (s, 3H), 3.92 (d, J = 8.1 Hz, 1H), 4.38 (d, J = 8.1 Hz, 1H), 7.18 (d, J = 1.5, 1H), 7.22 (dd, J =
8.3 and 1.5 Hz, 1H), 7.26−7.34 (m, 2H), 7.60−7.77 (m, 2H), 8.14 (d, J = 8.3 Hz, 1H), 13.24 (br s, 1H)
ppm. 13C NMR (125 MHz, THF-d8): C 18.7, 25.2, 27. 3, 37.5, 46.4, 80.9, 105.7, 111.7, 114.4, 117.0,
118.8, 119.3, 119.5, 123.4, 124.3, 125.5, 134.3, 140.6, 142.7, 152.5, 159.7 ppm. IR (KBr) : 3417, 3288,
2969, 2901, 1630, 1588, 1543 cm−1. Mass (m/z, %) : 395 (M++1, 19), 394 (M+, 67), 338 (20), 294 (15),
255 (11), 254 (27), 238 (19), 237 (100), 210 (27), 209 (28), 181 (19), 57 (22). HRMS (ESI) : 395.1947
calcd for C23H27N2O4 [M+H+] 395.1971. Anal. Calcd for C23H26N2O4: C, 70.03; H, 6.64; N, 7.10.
Found: C, 69.98; H, 6.75; N, 7.02.
5-tert-Butyl-1-[3-hydroxy-4-(N-methylbenzimidazol-2-yl)phenyl]-4,4-dimethyl-2,6,7-trioxabicyclo-
[3.2.0]heptane (2b): 94% yield. Pale yellow needles, mp 162.5−163.0 °C (dec.) (from CH2Cl2−hexane).
1H NMR (400 MHz, CDCl3): H 1.05 (s, 9H), 1.17 (s, 3H), 1.41 (s, 3H), 3,85 (d, J = 8.3 Hz, 1H), 4.09 (s,
3H), 4.61 (d, J = 8.3 Hz, 1H), 7.28 (dd, J = 8.5 and 1.8 Hz, 1H), 7.33−7.46 (m, 4H), 7.76−7.80 (m, 2H),
13.07 (br s, 1H) ppm. 13C NMR (125 MHz, CDCl3): C 18.4, 25.0, 26.9, 33.1, 36.7, 45.6, 80.3, 105.2,
109.6, 113.9, 116.2, 118.2, 118.4, 118.9, 123.1, 123.5, 126.4, 135.6, 139.2, 140.2, 150.9, 158.7 ppm. IR
(KBr): 3428, 2969, 2893, 1625, 1577 cm−1. Mass (m/z, %): 409 (M++1, 23), 408 (M+, 97), 352 (10), 308

HETEROCYCLES, Vol. 87, No. 1, 2013
75
(21), 278 (12), 268 (14), 267 (23), 252 (19), 251 (100), 224 (37), 223 (39), 195 (18), 57 (36). HRMS
(ESI): 409.2114 calcd for C24H29N2O4 [M+H+] 409.2127. Anal. Calcd for C24H28N2O4: C, 70.57; H, 6.91;
N, 6.86. Found: C, 70.26; H, 7.01; N, 6.85.
5-tert-Butyl-1-[3-hydroxy-4-(N-phenylbenzimidazol-2-yl)phenyl]-4,4-dimethyl-2,6,7-trioxabicyclo-
1
[3.2.0]heptane (2c): 96% yield. Colorless plates, mp 164.0−165.0 °C (dec.) (from CH2Cl2−hexane). H
NMR (500 MHz, CDCl3): H 0.99 (s, 9H), 1.13 (s, 3H), 1.34 (s, 3H), 3.78 (d, J = 8.4 Hz, 1H), 4.54 (d, J =
8.4 Hz, 1H), 6.81 (dd, J = 8.5 and 1.7 Hz, 1H), 6.87 (d, J = 8.5 Hz, 1H), 7.10 (d, J = 8.2 Hz, 1H),
7.25−7.30 (m, 5H), 7.58−7.64 (m, 3H), 7.81 (d, J = 7.9 Hz, 1H), 13.61 (br s, 1H) ppm. 13C NMR (125
MHz, CDCl3): C 18.4, 25.0, 26.9, 36.7, 45.6, 80.3, 105.1, 110.4, 113.1, 116.1, 117.9, 118.1, 118.7, 123.6,
124.0, 126.6, 127.8, 129.7, 130.4, 136.5, 136.9, 139.1, 139.9, 150.1, 159.2 ppm. IR (KBr): 3433, 3065,
2993, 2969, 2898, 1631, 1595, 1574 cm−1. Mass (m/z, %): 471 (M++1, 36), 470 (M+, 100), 414 (13),
370 (17), 330 (15), 329 (16), 314 (19), 313 (77), 286 (40), 285 (47), 257 (12), 256 (22), 255 (14), 57 (23).
HRMS (ESI): 471.2279 calcd for C29H31N2O4 [M+H+] 471.2284.
5-tert-Butyl-1-{4-[N-(4-carboxybutyl)benzimidazol-2-yl]-3-hydroxyphenyl}-4,4-dimethyl-2,6,7-
1
trioxabicyclo[3.2.0]heptane (2d): 99% yield. Pale yellow amorphous solid. H NMR (500 MHz,
CDCl3): H 1.05 (s, 9H), 1.17 (s, 3H), 1.41 (s, 3H), 1.74−1.83 (m, 2H), 2.01−2.10 (m, 2H), 2.44 (t, J = 7.3
Hz, 2H), 3.84 (d, J = 8.2 Hz, 1H), 4.41−4.49 (m, 2H), 4.60 (d, J = 8.2 Hz, 1H), 7.28 (dd, J = 8.2 and 1.8
13
Hz, 1H), 7.32−7.39 (m, 2H), 7.41−7.46 (m, 2H), 7.66 (d, J = 8.2 Hz, 1H), 7.76−7.79 (m, 1H) ppm. C
NMR (125 MHz, CDCl3): C 18.4, 21.7, 25.0, 26.9, 29.1, 33.1, 36.7, 45.3, 45.6, 80.3, 105.3, 109.8, 114.0,
116.2, 118.5, 118.6, 119.0, 123.3, 123.7, 125.8, 135.0, 139.4, 140.2, 150.3, 158.6, 178.4 ppm. IR (KBr):
3448, 2965, 1716, 1625, 1542 cm−1. Mass (m/z, %): 495 (M++1, 31), 494 (M+, 100), 478 (17), 477 (49),
435 (36), 422 (24), 421 (67), 409 (23), 408 (30), 394 (27), 338 (29), 337 (78), 319 (40), 310 (46), 309
(61), 281 (45), 254 (27), 237 (56), 181 (47), 57 (88). HRMS (ESI): 495.2485 calcd for C28H35N2O6
[M+H+] 495.2495.
Thermal decomposition of 2a to 2,2,4,4-tetramethyl-3-oxopentyl 4-(benzimidazol-2-yl)-3-
hydroxybenzoate (10a): Typical procedure. A solution of 2a (48.0 mg, 0.12 mmol) in p-xylene was
stirred under a nitrogen atmosphere at 140 °C for 3 h. After cooling, the reaction mixture was concentrated
in vacuo. The residue was chromatographed on silica gel and eluted with hexane−AcOEt to give 10a
(47.4 mg, 99%). 10a: Colorless granules, mp 285.0−286.0 °C (dec.) (from THF−hexane). 1H NMR (400
MHz, DMSO-d6): H 1.23 (s, 9H), 1.35 (s, 6H), 4.35 (s, 2H), 7.28−7.35 (m, 2H), 7.48 (d, J = 1.5 Hz, 1H),
7.53 (dd, J = 8.1 and 1.5 Hz, 1H), 7.66−7.74 (m, 2H), 8.21 (d, J = 8.1 Hz, 1H), 13.34 (br s, 1H) ppm. 13C
NMR (125 MHz, DMSO-d6): C 23.3, 28.0, 45.4, 48.8, 71.9, 112.3 (br), 117.1, 117.6, 118.2 (br), 119.6,
123.4 (br), 126.9, 131.9, 133.7 (br), 140.9 (br), 150.5, 157.8, 164.9, 215.5 ppm. IR (KBr) : 3347, 3318,
2969, 1709, 1681, 1612, 1582 cm−1. Mass (m/z, %) 395 (M++1, 19), 394 (M+, 70), 338 (18), 294 (14),
255 (11), 254 (27), 238 (18), 237 (100), 210 (25), 209 (25), 181 (19), 57 (24). HRMS (ESI) : 395.1980
calcd for C23H27N2O4 [M+H+] 395.1971. Anal. Calcd for C23H26N2O4: C, 70.03; H, 6.64; N, 7.10. Found:

76
HETEROCYCLES, Vol. 87, No. 1, 2013
C, 70.02; H, 6.78; N, 7.08.
2,2,4,4-Tetramethyl-3-oxopentyl 3-hydroxy-4-(N-methylbenzimidazol-2-yl)benzoate (10b): 94%
yield. Pale yellow columns, mp 174.0−175.0 °C (from CH2Cl2−hexane). 1H NMR (400 MHz, CDCl3): H
1.31 (s, 9H), 1.41 (s, 6H), 4.09 (s, 3H), 4.43 (s, 2H), 7.34−7.47 (m, 3H), 7.59 (dd, J = 8.3 and 1.7 Hz, 1H),
7.74 (d, J = 1.7 Hz, 1H), 7.76−7.82 (m, 2H), 13.13 (br s, 1H) ppm. 13C NMR (125 MHz, CDCl3): C 23.6,
28.1, 33.1, 45.9, 49.1, 72.2, 109.6, 116.7, 118.9, 119.0, 119.3, 123.2, 123.8, 126.7, 132.3, 135.6, 140.0,
150.4, 158.9, 165.5, 215.9 ppm. IR (KBr) : 3423, 3071, 2961, 1712, 1680, 1573 cm−1. Mass (m/z, %) :
409 (M ++1, 29), 408 (M+, 100), 352 (11), 308 (17), 268 (12), 267 (19), 252 (16), 251 (87), 224 (27), 223
(30), 195 (11), 57 (16). HRMS (ESI) : 409.2139 calcd for C24H29N2O4 [M+H+] 409.2127. Anal. Calcd for
C24H28N2O4: C, 70.57; H, 6.91; N, 6.86. Found: C, 70.28; H, 6.98; N, 6.91.
2,2,4,4-Tetramethyl-3-oxopentyl 3-hydroxy-4-(N-phenylbenzimidazol-2-yl)benzoate (10c): 97%
yield. Pale yellow columns, mp 180.5−181.0 °C (from CH2Cl2−hexane). 1H NMR (400 MHz, CDCl3): H
1.27 (s, 9H), 1.37 (s, 6H), 4.37 (s, 2H), 6.89 (d, J = 8.4 Hz, 1H), 7.10−7.15 (m, 2H), 7.28−7.44 (m, 4H),
13
7.62−7.66 (m, 3H), 7.68 (d, J = 1.6 Hz, 1H), 7.84 (d, J = 7.9 Hz, 1H), 13.67 (br s, 1H) ppm. C NMR
(125 MHz, CDCl3): C 23.6, 28.2, 45.8, 49.1, 72.1, 110.5, 116.1, 118.8, 118.9, 119.0, 123.7, 124.3, 127.1,
127.8, 129.8, 130.5, 132.2, 136.5, 136.8, 139.8, 149.7, 159.4, 165.6, 215.9 ppm. IR (KBr) : 3431, 3060,
2971, 2874, 1724, 1685, 1579 cm−1 Mass (m/z, %): 471 (M++1, 36), 470 (M+, 100), 414 (14), 370 (24),
.
330 (18), 329 (22), 314 (21), 313 (86), 287 (11), 286 (53), 285 (64), 257 (20), 256 (34), 255 (20), 57 (30).
HRMS (ESI): 471.2278 calcd for C29H31N2O4 [M+H+] 471.2284.
2,2,4,4-Tetramethyl-3-oxopentyl
4-[N-(4-carbonylbutyl)benimidazol-2-yl]-3-hydroxybenzoate
1
(10d): 82% yield. Pale yellow amorphous solid. H NMR (500 MHz, CDCl3): H 1.30 (s, 9H), 1.41 (s,
6H), 1.75−1.83 (m, 2H), 2.02−2.10 (m, 2H), 2.45 (t, J = 7.1 Hz, 2H), 4.42 (s, 2H), 4.42−4.49 (m, 2H),
7.33−7.40 (m, 2H), 7.43−7.47 (m, 1H), 7.59 (dd, J = 8.2 and 1.8 Hz, 1H), 7.69 (d, J = 8.2 Hz, 1H), 7.73
(d, J = 1.8 Hz, 1H), 7.77−7.80 (m, 1H) ppm. 13C NMR (125 MHz, CDCl3): C 21.7, 23.6, 28.1, 29.1, 33.1,
45.3, 45.9, 49.1, 72.2, 109.9, 116.9, 119. 1, 119.2, 119.6, 123.4, 123.9, 126.4, 132.4, 135.0, 140.0, 149.8,
158.7, 165.5, 178.1, 216.1 ppm. IR (KBr) : 2970, 2932, 2877, 1719, 1704, 1684, 1525, cm−1. Mass
(m/z, %) : 495 (M++1, 34), 494 (M+, 100), 493 (41), 477 (54), 435 (36), 421 (64), 408 (25), 337 (58), 319
(84), 309 (37), 292 (39), 237 (34), 57 (60). HRMS (ESI) : 495.2481 calcd for C28H35N2O6 [M+H+]
495.2495.
Measurement of chemiluminescence and time-course of the base-induced decomposition of
dioxetanes; General Procedure: Chemiluminescence was measured using a JASCO FP-750 and/or
FP-6500 spectrometer, and a Hamamatsu Photonics PMA-11 multi-channel detector.
TBAF/MeCN system. A freshly prepared solution (2.00 mL) of TBAF (1.0 x 10−2 mol/L) in MeCN was
transferred to a quartz cell (10 x 10 x 50 mm), which was placed in a spectrometer that was thermostated
with stirring at 45 °C. After 3−5 min, a solution of dioxetane 2 in MeCN (1.0 x 10−5 mol/L, 1.00 mL)

HETEROCYCLES, Vol. 87, No. 1, 2013
77
was added by means of a syringe, and measurement was started immediately. The time-course of the
intensity of light emission was recorded and processed according to first-order kinetics. The total light
emission was estimated by comparing it with that of an adamantylidene dioxetane, the chemiluminescent
efficiency CL of which has been reported to be 0.29 and which was used here as a standard.12,13
NaOH/H2O system. A solution of NaOH (0.1 M, 2.90 mL) in H2O was transferred to a quartz cell (10 x
10 x 50 mm), which was placed in a spectrometer that was thermostated with stirring at 45 °C. After
3−5 min, a solution of dioxetane 2 in MeCN (1.0 x 10−4 mol/L, 0.10 mL) was added by means of a
syringe, and measurement was started immediately. The time-course of the intensity of light emission was
recorded and processed according to first-order kinetics.
ACKNOWLEDGEMENTS
The authors gratefully acknowledge financial assistance in the form of Grants-in-aid (No. 21550052 and
No. 22550046) for Scientific Research from the Ministry of Education, Culture, Sports, Science, and
Technology, Japan.
REFERENCES AND NOTES
1. (a) A. P. Schaap and S. D. Gagnon, J. Am. Chem. Soc., 1982, 104, 3504; (b) A. P. Schaap, R. S.
Handley, and B. P. Giri, Tetrahedron Lett., 1987, 28, 935; (c) A. P. Schaap, T. S. Chen, R. S.
Handley, R. DeSilva, and B. P. Giri, Tetrahedron Lett., 1987, 28, 1155.
2. (a) J.-Y. Koo and G. B. Schuster, J. Am. Chem. Soc., 1977, 99, 6107; (b) J.-Y. Koo and G. B.
Schuster, J. Am. Chem. Soc., 1978, 100, 4496; (c) W. Adam, I. Bronstein, T. Trofimov, and R. F.
Vasil’ev, J. Am. Chem. Soc., 1999, 121, 958; (d) W. Adam, M. Matsumoto, and T. Trofimov, J. Am.
Chem. Soc., 2000, 122, 8631; (e) A. L. P. Nery, D. Weiss, L. H. Catalani, and W. J. Baader,
Tetrahedron, 2000, 56, 5317.
3. (a) L. H. Catalani and T. Wilson, J. Am. Chem. Soc., 1989, 111, 2633; (b) F. J. McCapra, Photochem.
Photobiol. A. Chem., 1990, 51, 21; (c) T. Wilson, Photochem. Photobiol., 1995, 62, 601.
4. (a) Y. Takano, T. Tsunesada, H. Isobe, Y. Yoshioka, K. Yamaguchi, and I. Saito, Bull. Chem. Soc.
Jpn., 1999, 72, 213; (b) J. Tanaka, C. Tanaka, and M. Matsumoto, PCCP, 2011, 13, 16005; (c) H.
Isobe, Y. Takano, M. Okumura, S. Kuramitsu, and K. Yamaguchi, J. Am. Chem. Soc., 2005, 127,
8667.
5. (a) S. Beck and H. Köster, Anal. Chem., 1990, 62, 2258; (b) W. Adam, D. Reihardt, and C. R.
Saha-Möller, Analyst, 1996, 121, 1527.
6. (a) M. Matsumoto, J. Photochem. Photobiol. C: Photochem. Rev., 2004, 5, 27; (b) M. Matsumoto
and N. Watanabe, Bull. Chem. Soc. Jpn., 2005, 78, 1899.
7. B. Edwards, A. Sparks, J. C. Voyta, and I. Bronstein, ‘Bioluminescence and Chemiluminescence,
Fundamentals and Applied Aspects’, ed. by A. K. Campbell, L. J. Kricka, and P. E. Stanley, Wiley,

78
HETEROCYCLES, Vol. 87, No. 1, 2013
Chichester, 1994, pp. 56–59.
8. (a) M. Matsumoto, T. Akimoto, Y. Matsumoto, and N. Watanabe, Tetrahedron Lett., 2005, 46,
6075; (b) M. Tanimura, N. Watanabe, H. K. Ijuin, and M. Matsumoto, J. Org. Chem., 2010, 75,
3678.
9. M. Tanimura, N. Watanabe, H. K. Ijuin, and M. Matsumoto, J. Org. Chem., 2011, 75, 902.
10. M. Matsumoto, T. Sakuma, and N. Watanabe, Luminescence, 2001, 16, 275.
11. (a) A. R. Katrizky, Tetrahedron, 1980, 36, 679; (b) A. R. Katrizky and C. M. Marson, Angew. Chem.
Int. Ed. Engl., 1984, 23, 420; (c) A. R. Katrizky and G. Musumara, Chem. Soc. Rev., 1984, 13, 47;
(d) A. R. Katrizky, K. Sakizadeh, and G. Musumara, Heterocycles, 1985, 23, 1765.
12. CL was estimated based on the value 0.29 for the chemiluminescent decomposition of 3-(3-tert-
butyldimethylsiloxyphenyl)-3-methoxy-4-(2’-spiroadamantane)-1,2-dioxetane in a TBAF/DMSO
system.13
13. A. V. Trofimov, K. Mielke, R. F. Vasil’ev, and W. Adam, Photochem. Photobiol., 1996, 63, 463.
14. M. Matsumoto, Y. Mizoguchi, T. Motoyama, and N. Watanabe, Tetrahedron Lett., 2001, 42, 8869.