New triggering system for dioxetane-based chemiluminescence: Base-induced decomposition of bicyclic dioxetanes bearing a 3-aminophenyl or 2-phenylindol-6-yl moiety

Article abstract of DOI:10.1246/cl.2005.718

A dioxetane substituted with a 3-aminophenyl group was deprotonated with t-BuOK in DMSO to give an unstable dioxetane bearing a phenylamide anion, which decomposed with accompanying emission of flash red light. Dioxetane bearing an indol-6-yl group was sy

Full text of DOI:10.1246/cl.2005.718

718
Chemistry Letters Vol.34, No.5 (2005)
New Triggering System for Dioxetane-based Chemiluminescence: Base-induced
Decomposition of Bicyclic Dioxetanes Bearing a 3-Aminophenyl or 2-Phenylindol-6-yl Moiety
Nobuko Watanabe, Miho Ichikawa, Ayumi Ono, Hiroyuki Murakami, and Masakatsu Matsumotoꢀ
Department of Chemistry, Kanagawa University, Tsuchiya, Hiratsuka 259-1293
(Received March 9, 2005; CL-050318)
A dioxetane substituted with a 3-aminophenyl group was
deprotonated with t-BuOK in DMSO to give an unstable dioxe-
tane bearing a phenylamide anion, which decomposed with ac-
companying emission of flash red light. Dioxetane bearing an in-
dol-6-yl group was synthesized and found to exhibit emission of
flash blue light on treatment with tetrabutylammonium fluoride
as well as with t-BuOK.
ple 3-aminophenyl group, synthesis of which has been reported
already.5 The second was dioxetanes bearing a 3-acetyl-
aminophenyl 2a or 3-benzoylaminophenyl group 2b, whose syn-
thesis was easily attained by the singlet oxygenation of the cor-
responding dihydrofurans 4a, 4b6,7 in high yield. The third was
dioxetane 3 bearing a 2-phenylindol-6-yl moiety, in which a 2-
phenyl group was introduced to decrease the reactivity of the in-
dole ring toward singlet oxygenation used for the synthesis of 3
from a key intermediate 5. Dihydrofuran having a 2-phenylin-
dol-6-yl moiety 5 was synthesized by intramolecular cyclization
of N-benzoyl-o-toluidine 6: on treatment with BuLi at 50 ꢂC, 6
was converted into 5 in 55% isolated yield.8 An amide 6 was
synthesized by transformation of a bromophenyl group in dihy-
drofuran 7 to a benzoylamino group through a toluidine deriva-
tive 8 in 86% total yield. When a solution of dihydrofuran 5 and
a catalytic amount of tetraphenylporphin in CH2Cl2 was irradi-
ated externally with a 940-W Na lamp under an O2 atmosphere
at ꢁ78 ꢂC for 2 h, dioxetane 3 was produced exclusively and was
isolated as pale yellow granules (mp 223.9–224.9 ꢂC) after chro-
matographic purification (SiO2/ether-hexane). The structures of
dioxetanes 2 and 3 were determined by 1H NMR, 13C NMR, IR,
HRMass spectral analysis.9 On heating in hot toluene, these di-
oxetanes 1–3 decomposed exclusively to ketoesters 9–11, re-
spectively, though they were quite stable to permit handling at
room temperature.
Dioxetanes substituted with an aromatic electron donor such
as an oxyanion of a hydroxyarene moiety (ArOꢁ) undergo intra-
molecular charge-transfer (CT)-induced decomposition with ac-
companying emission of light.1–4 The phenomenon has received
much attention, and extensive research efforts have been made to
elucidate the chemiexcitation pathways as well as to develop
efficient chemiluminescent systems.1,2 However, there has
been little known of dioxetanes bearing an amide anion such
as an arylamide anion (Ar(Y)Nꢁ) instead of an aryloxide anion
(ArOꢁ), though Ar(Y)Nꢁ would act as an electron donor similar
to ArOꢁ for the intramolecular CT-induced decomposition
(Scheme 1). This situation prompted us to design a new type
of dioxetane bearing an Ar(Y)NH moiety, from which a proton
is abstracted with a base to generate an arylamide anion
(Ar(Y)Nꢁ).
We chose three types of dioxetanes bearing an Ar–NH–Y
moiety to be examined. The first was dioxetane 1 bearing a sim-
When a solution of dioxetane 1 in DMSO (1:0 ꢃ 10ꢁ4 M,
1 mL) was added to a solution of t-BuOK in DMSO (1:0 ꢃ
10ꢁ1 M, 2 mL) at 25 ꢂC, 1 decomposed rapidly to give ketoester
9 with accompanying emission of flash red light with maximum
wavelength (ꢀmaxCL) = 642 nm, chemiluminescence efficiency
O O
CT
*
O
O Ar
Ar
O
O
Light
Ph
Y
N
H
N
H
O O
t-Bu
t-Bu
CT
O
?
*
O
O
O
5
N Ar
Y
Ar
N
Y
4a:Y = CH3CO-
4b:Y = PhCO-
Light
iii)
Scheme 1. Intramolecular CT-induced chemiluminescent de-
composition of dioxetanes.
Me
X
Me
PhCO
ii)
N
H
t-Bu
t-Bu
O
O
O
O
t-Bu
O
O
t-Bu
6
O
Y
7: X = Br
8: X = NH2
Ph
N
H
O
N
H
i)
1: Y = H
3
Reagents: i) BuLi / TsN3, Ph3P / H2O, ii) PhCOCl,
iii) BuLi / THF / ∆
2a:Y = CH3CO-
2b:Y = PhCO-
Scheme 2. Dioxetanes bearing a 3-aminophenyl or indol-6-yl
group.
Scheme 3. Synthesis of key intermediate 5 for the synthesis of
dioxetane 3.
Copyright Ó 2005 The Chemical Society of Japan

Chemistry Letters Vol.34, No.5 (2005)
719
ðꢀCLÞ ¼ 4:8 ꢃ 10ꢁ6, and rate constant for CT-induced decom-
position following pseudo-first order kinetics ðkDICTÞ ¼
1:4 sꢁ1. The chemiluminescent properties for 1 were significant-
higher ꢀCL, longer ꢀmax and slower rate (kDICT) than those
for dioxetanes with ‘‘even’’ pattern.4
CL
In conclusion, the present studies show that a dioxetane sub-
stituted with a 3-aminophenyl group can be triggered with a base
to give an unstable dioxetane bearing a phenylamide anion,
which decomposes with accompanying emission of flash red
light. Decomposition of a dioxetane bearing an indol-6-yl group
was shown to be induced with a base to give flash blue light.
These results provide an entry to dioxetane-based chemilumi-
nescent substrates with a new triggering system.
ly different from those for dioxetane 12 bearing a 3-(t-butydime-
CL
thylsiloxy)phenyl, which emits bright blue light with ꢀmax
¼
10
466 nm, ꢀCL ¼ 0:20, and kDICT ¼ 0:15 sꢁ1
.
Furthermore,
differently than 12, decomposition of dioxetane 1 was not in-
duced by treatment with TBAF in DMSO, which is frequently
used as a triggering system for dioxetanes active toward the
intramolecular CT-induced chemiluminescent decomposition.4
This difference would be due to the fact that aniline is a very
weak acid: pKa ¼ 30:6 for aniline in DMSO at 25 ꢂC.11,12
O O
O O
:B
t-Bu
t-Bu
3
Ph
Ph
O
O
N
O O
N
O O
t-Bu
t-Bu
13: "odd" patern
14: "even" patern
Ph
O
N
H
O
Y
N
H
Scheme 5. Intermediary dioxetane produced from 3.
11
9: Y = H
10a: Y = CH3CO-
10b: Y = PhCO-
O
O
The authors gratefully acknowledge financial assistance
t-Bu
provided by a Grant-in aid (No. 15550043 and No. 14540506)
for Scientific Research by the Ministry of Education, Culture,
Sports, Science, and Technology, Japan.
O
t-BuMe2SiO
12
Scheme 4. Ketoesters 9–11 and parent dioxetane 12.
References and Notes
1
On the other hand, anilides such as acetanilide are presum-
ably a far stronger acid (pKa ¼ 21:45 for acetanilde)11 than ani-
line, so that deprotonation of dioxetanes 2a and 2b would take
place much more easily than 1 to give the corresponding acyl-
amide anions. However, the expected CT-induced decomposi-
tion of 2 itself occurred sluggishly to emit little observable light.
Indole is also an acid as strong as acetanilide (pKa ¼
20:95).11 When dioxetane 3 was treated with a large excess of
t-BuOK in DMSO similarly to the case of 1, 3 decomposed to
A. P. Schaap, T.-S. Chen, R. S. Handley, R. DeSilva, and
B. P. Giri, Tetrahedron Lett., 28, 1155 (1987).
2
3
S. Beck and H. Koster, Anal. Chem., 62, 2258 (1990).
¨
W. Adam, D. Reinhardt, and C. R. Saha-Moller, Analyst,
121, 1727 (1996).
¨
4
5
M. Matsumoto, J. Photochem. Photobiol., C, 5, 27 (2004).
M. Matsumoto, H. Murakami, and N. Watanabe, J. Chem.
Soc., Chem. Commun., 1998, 2319.
6
5-Aryl-4-t-butyl-3,3-dimethyl-2,3-dihydrofurans 4a, 4b,
and 7 were synthesized from 7-aryl-2,2,4,4-tetramethyl-6-
oxoheptan-3-ones, according to the method reported.7
M. Matsumoto, Y. Ito, M. Murakami, and N. Watanabe,
Luminescence, 17, 305 (2002).
emit flash blue light with ꢀmax ¼ 457 nm, ꢀCL ¼ 3:4 ꢃ
CL
10ꢁ5, and kDICT ¼ 7:7 sꢁ1. The chemiluminescent decomposi-
tion of 3 occurred to give a quite similar result on treatment with
TBAF in place of t-BuOK in DMSO. The chemiluminescent
spectrum of 3 in t-BuOK or TBAF/DMSO coincided with the
fluorescence spectrum of the spent reaction mixture, from which
ketoester 11 was isolated after neutralization in high yield. The
fluorescence spectrum of authentic ketoester 11 coincided also
with the chemiluminescent spectrum of 3 in TBAF/DMSO.
The chemiluminescent efficiency (ꢀCL) was rather lower
than that of our expectation. Since the efficiency of fluorescence
(ꢀfl) for the emitter, namely, ketoester 11, was estimated to be
0.39 in TBAF/DMSO, the efficiency of singlet-chemiexcitation
(ꢀS) was estimated to be only 8:7 ꢃ 10ꢁ5 for the chemilumines-
cent decomposition of 3. This fact is most likely accounted for
by the idea that amide anion 13 produced from dioxetane 3 by
triggering with a base would be an ambident anion including
13 and carbanion 14 as canonical structures, as is well-known
for indoles. Applying dioxetane 3 to the ‘‘odd/even’’ relation-
7
8
9
W. J. Houlihan, V. A. Parino, and Y. Uike, J. Org. Chem.,
46, 4511 (1981).
Selected data for 3: 1H NMR (400 MHz, CDCl3) ꢁH 1.01 (s,
9H), 1.18 (s, 3H), 1.43 (s, 3H), 3.85 (d, J ¼ 8:2 Hz, 1H), 4.62
(d, J ¼ 8:2 Hz, 1H), 6.83 (s with fine coupling, 1H), 7.31–
7.37 (m, 2H), 7.43–7.48 (m, 2H), 7.62 (d, J ¼ 8:3 Hz, 1H),
7.66–7.70 (m, 2H), 7.79 (s, 1H), 8.50 (broad s, 1H) ppm;
13C NMR (125 MHz, CDCl3) ꢁC 18.7, 25.1, 26.9, 36.9,
45.7, 80.1, 99.6, 105.2, 111.7, 117.7, 120.0, 120.2, 125.2,
127.8, 128.9, 129.5, 129.8, 132.0, 136.1, 139.4 ppm;
HRMass (ESI) m=z found 400.1889, calcd for C24H27NaO3
[M þ Naþ] 400.1861.
10 M. Matsumoto, Y. Ito, J. Matsubara, T. Sakuma, Y.
Mizoguchi, and N. Watanabe, Tetrahedron Lett., 42, 2349
(2001).
ship between the substitution pattern of the anion on the
aromatic ring and chemiluminescent properties (ꢀCL, ꢀmax
k
11 R. W. Taft and F. G. Bordwell, Acc. Chem. Res., 21, 463
(1988).
CL
,
DICT) for base-induced decomposition of dioxetanes, the amide
12 Amide anion of 9 is most likely the emitter for the chemilu-
minescent decomposition of 1, though 9 exhibited little flu-
anion 13 is ‘‘odd’’ pattern, though the canonical structure of
carbanion 14 is unfortunately ‘‘even’’ pattern. It has been known
for dioxetanes bearing an aromatic electron donor active toward
the intramolecular CT-induced decomposition, that dioxetanes
with ‘‘odd’’ pattern tend to exhibit chemiluminescence with
CL
orescence with ꢀmax ¼ 642 nm in t-BuOK/DMSO, in
which the expected amide anion was presumably generated
not in sufficient concentration because of very low acidity
of 9.
Published on the web (Advance View) April 16, 2005; DOI 10.1246/cl.2005.718