Fluoride-induced chemiluminescent decomposition of 1,2-dioxetanes bearing a phenyl moiety substituted with a methyl having an electron-withdrawing group

Article abstract of DOI:10.1039/b210857g

A new type of dioxetane bearing a 3-(cyanomethyl)phenyl (1a), 3-(methoxycarbonylmethyl)phenyl (1b), 3-(benzoylmethyl)phenyl (1c), or 3-[cyano(methoxycarbonyl)methyl]phenyl group (1d) decomposed through an intermediary dioxetane bearing a benzylic carbanio

Full text of DOI:10.1039/b210857g

Fluoride-induced chemiluminescent decomposition of 1,2-dioxetanes
bearing a phenyl moiety substituted with a methyl having an
electron-withdrawing group†
Masakatsu Matsumoto,* Toshiyuki Mizuno and Nobuko Watanabe
Department of Materials Science, Kanagawa University, Tsuchiya, Hiratsuka, Kanagawa 259-1293, Japan.
E-mail: matsumo@chem.kanagawa-u.ac.jp; Fax: +81-463-59-4111; Tel: +81-463-58-9684
Received (in Cambridge, UK) 6th November 2002, Accepted 13th January 2003
First published as an Advance Article on the web 27th January 2003
A new type of dioxetane bearing a 3-(cyanomethyl)phenyl
(1a), 3-(methoxycarbonylmethyl)phenyl (1b), 3-(benzoylme-
thyl)phenyl (1c), or 3-[cyano(methoxycarbonyl)methyl]phe-
nyl group (1d) decomposed through an intermediary dioxe-
tane bearing a benzylic carbanion to afford crimson to yellow
light on treatment with TBAF in DMSO.
purification [SiO2/hexane–CH2Cl2 (1+1)]. The structure of
dioxetane (1a) was determined by 1H NMR, 13C NMR, IR, and
HRMass spectral analysis.§ Methoxycarbonylmethyl- (1b),
benzoylmethyl- (1c), and cyano(methoxycarbonyl)methyl-ana-
logs (1d) were similarly synthesized from the corresponding
dihydrofurans (2b–2d) in 86, 90, and 94% isolated yield,
respectively. All dioxetanes (1a–1d) synthesized here were
stable enough to permit handling at room temperature, though
they decomposed to give the corresponding keto-esters (3a–3d)
exclusively in refluxing p-xylene.
Dioxetanes substituted with an aromatic electron donor such as
an oxyanion of a hydroxyarene (aryl-O2) moiety undergo
intramolecular charge-transfer (CT)-induced decomposition
with accompanying luminescence.1–5 The phenomenon has
received much attention from the viewpoint of mechanistic
interest related to bioluminescence and application to chem-
iluminescent bioassays, and extensive research efforts have
been made to elucidate the chemiexcitation pathways as well as
to develop efficient chemiluminescent systems.6,7 However,
there has been little known of dioxetanes bearing a carbanion
such as a benzylic anion (aryl-C2) instead of an aryloxy anion
(aryl-O2), though a benzylic carbanion would play a role of
electron donor similar to an aryloxy anion for the intramolecular
CT-induced chemiluminescent decomposition (Scheme 1). This
situation prompted us to design a new type of dioxetane (1)
(Scheme 2) bearing a phenyl moiety substituted with a methyl
having an electron-withdrawing group(s) (-CH2-Ew or X-CH-
Ew), of which a proton is easily abstracted with a base to afford
a benzylic carbanion, and it was found that these dioxetanes (1)
decompose rapidly to afford crimson to yellow light on
treatment with tetrabutylammonium fluoride (TBAF) in
DMSO.
The designed dioxetanes were 5-tert-butyl-4,4-dimethyl-
2,6,7-trioxabicyclo[3.2.0]heptanes‡8 bearing a 3-(cyanome-
thyl)phenyl (1a), 3-(methoxycarbonylmethyl)phenyl (1b),
3-(benzoylmethyl)phenyl (1c), or 3-[cyano(methoxycarbonyl-
)methyl]phenyl group (1d) at the 1-position. When a 4-tert-
butyl-3,3-dimethyl-2,3-dihydrofuran bearing a 3-(cyanome-
thyl)phenyl at the 5-position (2a) (200 mg) was irradiated in the
presence of tetraphenylporphin (TPP, 1 mg) with a 940-W Na
lamp in CH2Cl2 (10 mL) under O2 atmosphere at 0 °C for 1 h,
the desired dioxetane (1a) was produced as pale yellow granules
(mp 99.8–100.6 °C) in 89% yield after chromatographic
When a solution of a dioxetane (1a) in DMSO (1 3 1023 mol
dm23, 1 mL) was added to a solution of tetrabutylammonium
fluoride (TBAF)¶ 9 in DMSO (0.1 mol dm23, 2 mL) at 25 °C,
1a decomposed rapidly to emit flash crimson light (maximum
CL
wavelength: lmax = 702 nm, chemiluminescence efficiency:
FCL = 3.3 3 1025,∑ 10 half-life: t1/2 < 0.02 s).** On treatment
with TBAF in DMSO similarly to the case of 1a, the other
dioxetanes (1b–1d) also decomposed to exhibit chemilumines-
cence, of which the properties are summarized together with
those for 1a in Table 1. It is noteworthy that a dioxetane (1d)
exhibits chemiluminescence with far higher efficiency (FCL),
far longer half-life (t1/2), and far shorter maximum wavelength
of the emission (lmaxCL) than those for the others (1a–1c).
The fresh spent reaction mixture of TBAF-induced chem-
iluminescent decomposition for all dioxetanes (1a–1d) in
DMSO was confirmed to include the corresponding keto-esters
(3a–3d) exclusively.†† On the other hand, fluorescence of the
spent reaction mixture was observed only for 1d, while little
was unfortunately observed for the other dioxetanes (1a–1c).
CL
The maximum wavelength of the chemiluminescence (lmax )
for 1d coincided with the maximum wavelength of the
fluorescence (lmaxfl) for the spent reaction mixture in TBAF–
DMSO. The authentic keto-ester (3d), prepared by thermolysis
Scheme 1
† Electronic supplementary information (ESI) available: experimental
section. See http://www.rsc.org/suppdata/cc/b2/b210857g/
Scheme 2
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CHEM. COMMUN., 2003, 482–483
This journal is © The Royal Society of Chemistry 2003

of 1d, showed fluorescence with efficiency Ffl = 0.018 and its
maximum wavelength (lmaxfl)‡‡ coincided also with lmaxCL of
the chemiluminescence for 1d in TBAF–DMSO. Furthermore,
when a solution of a keto-ester (3d) in TBAF–DMSO was
treated with methyl iodide, a product methylated at the benzylic
position (6d) was produced exclusively. These facts reveal that
the emitter produced is undoubtedly a carbanion of 3d, namely
The results presented here show a first example that a
dioxetane bearing a phenyl group substituted with an acidic
methylene or methyne undergoes base-induced chemilumines-
cent decomposition through an intermediary dioxetane bearing
a benzylic carbanion by a mechanism similar to the case of CT-
induced chemiluminescent decomposition of a dioxetane bear-
ing an aryloxy anion. Finally, it should be noted here that a
dioxetane bearing a 4-(cyanomethyl)phenyl (8) decomposed as
easily as its 3-(cyanomethyl)phenyl-isomer (1a) but gave little
light. This tendency resembles the case of dioxetanes bearing an
oxyphenyl anion, for which a 4-oxyphenyl-analog has been
known to emit light far less effectively than a 3-oxyphenyl-
analog.6,12
5d, and thus, the singlet-chemiexcitation efficiency (FS = FCL
/
Ffl) is estimated to be FS = 0.32 for the TBAF-induced
decomposition of 1d. The emitter would be the respective
benzylic carbanion of the keto-ester (3a–3c) also for the TBAF-
induced chemiluminescent decomposition of the other dioxe-
tanes (1a–1c), though little fluorescence was observed even for
the authentic keto-ester (3a–3c) in TBAF–DMSO.
When TBAF was absent in DMSO, little chemiluminescent
decomposition occurred for all dioxetanes (1a–1d), while it
took place easily also on treatment with a base such as t-BuOK
instead of TBAF. Considering this fact and that a benzylic
carbanion of 3 would be an emitter, it is reasonable to assume
that proton-abstraction from 1 with TBAF produces an unstable
dioxetane (4) bearing a benzylic carbanion, from which CT
occurs to induce the decomposition of the dioxetane ring
producing an excited carbanion (5) of the keto-ester by a
mechanism similar to the case of a dioxetane bearing an aryloxy
anion,1–5 as illustrated in Scheme 3.
From an analogy of the CT-induced decomposition of a
dioxetane bearing an aryloxy anion, it is inferred that chem-
iluminescent decomposition of a dioxetane (4) bearing a
benzylic carbanion produced from 1 is expected to occur more
easily, as the benzylic carbanion becomes less stable and is
more easily oxidized. This idea is apparently consistent with the
fact that the half-life of chemiluminescence (t1/2 = loge 2/k, k:
rate constant of TBAF-induced decomposition) becomes longer
in the order of 1a < 1b < 1c < 1d (Table 1): considering the
order of acidity for the parent carbon acids,11 namely, CH3CN
(pKa = 25) < CH3CO2Me (pKa = 24.5) < CH3COPh (pKa =
19) < < CH2(CN)CO2Me (pKa = 9), the acidity of a benzylic
position for 1 increases presumably in the order of 1a < 1b <
1c < 1d, so that the stability of their conjugate carbanions
increases in the same order.
The authors gratefully acknowledge financial assistance
provided by a grant-in-aid for Scientific Research by the
Ministry of Education, Science, Sports and Culture.
Notes and references
‡ 1-Aryl-5-tert-butyl-4,4-dimethyl-2,6,7-trioxabicyclo[3.2.0]heptane has
been recently reported to provide a thermally persistent dioxetane
skeleton.8
§ Selected data for 1a: dH(400 MHz, CDCl3) 0.98 (s, 9H), 1.16 (s, 3H), 1.39
(s, 3H), 3.79 (s, 2H), 3.83 (d, J = 8.2 Hz, 1H), 4.59 (d, J = 8.2 Hz, 1H), 7.39
(d, J = 7.6 Hz, 1H), 7.44 (t, J = 7.6 Hz, 1H), 7.59 (s, 1H), 7.62 (d, J = 7.6
Hz, 1H); dC(100 MHz, CDCl3) 18.5, 23.7, 25.2, 26.8, 36.7, 45.7, 80.3,
104.9, 116.2, 117.4, 127.8, 128.1, 128.7, 128.9, 129.7, 137.1; Mass (m/z, %)
302 (M+ + 1, 2), 269 (7), 244 (40), 218 (52), 162 (48), 144 (89), 85 (66), 57
(100). Anal. Calcd. for C18H23NO3: C, 71.73; H, 7.69; N, 4.65. Found: C,
71.86; H, 8.08; N, 4.73.
¶ TBAF has been widely used as a strong base for carbanion-participated
reactions such as aldol condensation and Michael addition in an aprotic
solvent.9
∑ Chemiluminescence yields (FCL) were based on the reported value for
TBAF-induced chemiluminescent decomposition of 3-(2A-spiroadaman-
tane)-4-methoxy-4-(3A-tert-butyldimethylsiloxy)phenyl-1,2-dioxetane in
TBAF: FCL = 0.29.10
** Preliminary kinetic experiments showed that chemiluminescent decom-
position of 1 occurred following pseudo-first-order kinetics independent of
the TBAF concentration, when a large excess of TBAF ( > 100 eq.) was
used.
†† Keto-ester (3) changed gradually into a complex mixture including
products of aldol and/or Claisen condensation on standing at room
temperature in TBAF–DMSO.
Table 1 TBAF-induced chemiluminescent decomposition of dioxetanes
(1a–1d) in DMSOa
‡‡ Quinine bisulfate was used as the fluorescence standard.
Dioxetane (1)
lmax
nm
/
Ew
X
t1/2
s
FCLb
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1a
1b
1c
1d
-CN
H
H
H
702
666
622
530
< 0.02
0.42
0.43
3.3 3 1025
4.0 3 1025
4.4 3 1024
5.7 3 1023
-CO2Me
-COPh
-CN
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-CO2Me
2300
a A solution of a dioxetane (1) in DMSO (1 3 1023 mol dm23, 1 mL) was
added to a solution of TBAF in DMSO (0.1 mol dm23, 2mL) at 25 °C.
b Chemiluminescence yields (FCL) were based on the reported value for
TBAF-induced chemiluminescent decomposition of 1,2-dioxetane in
TBAF: FCL = 0.29 (ref. 10).
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Scheme 3
CHEM. COMMUN., 2003, 482–483
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