New acridone-and (Thio)xanthone-derived 1,1-donor–acceptor-substituted alkenes: Ph-dependent fluorescence and unusual photooxygenation properties

Article abstract of DOI:10.3390/molecules26113305

A synthetic route to new heterocyclic 1,1-donor–acceptor-substituted alkenes starting with N-methyl-acridone, xanthone, and thioxanthone was investigated, leading to the acridone-and xanthone-derived products methyl 2-methoxy-2-(10-methylacridin-9 (10H)-ylidene)acetate (7) and methyl 2-methoxy-2-(9H-xanthen-9-ylidene)acetate (10) in low yields with the de-methoxylated product methyl 2-(10-methylacridin-9 (10H)-ylidene)acetate (8) and the reduced compound methyl 2-methoxy-2-(9H-xanthen-9-yl)acetate (11) as the major products from N-methyl acridone and xanthone. From thioxanthone, only the rearrangement and reduction products (14) and (15) resulted. The photophysical properties of compounds (7), (8), and (10) were investigated in the presence and absence of the Br?nsted acid TFA by NMR, UV–VIS absorption, and fluorescence spectroscopy. Protonation of the acridone-derived alkenes (7) and (8) led to strong bathochromic and hyperchromic fluorescence shifts and a substantial increase in Stokes shift. The photooxygenation experiments with these substrates showed an unusual reactivity pattern in the singlet oxygen processes: whereas the electron-rich enolether (7) was chemically unreactive, (8) and (10) were oxidatively cleaved, presumably via intermediate 1,2-dioxetanes.

Full text of DOI:10.3390/molecules26113305

molecules
Communication
New Acridone- and (Thio)Xanthone-Derived
1,1-Donor–Acceptor-Substituted Alkenes: pH-Dependent
Fluorescence and Unusual Photooxygenation Properties
Tim Lippold, Jörg M. Neudörfl and Axel Griesbeck *
Department of Chemistry, Faculty of Natural Sciences and Mathematics, University of Cologne, Greinstr. 4-6,
50939 Köln-Cologne, Germany; lippoldt@smail.uni-koeln.de (T.L.); aco48@uni-koeln.de (J.M.N.)
* Correspondence: griesbeck@uni-koeln.de
Abstract: A synthetic route to new heterocyclic 1,1-donor–acceptor-substituted alkenes starting with
N-methyl-acridone, xanthone, and thioxanthone was investigated, leading to the acridone- and
xanthone-derived products methyl 2-methoxy-2-(10-methylacridin-9 (10H)-ylidene)acetate (
methyl 2-methoxy-2-(9H-xanthen-9-ylidene)acetate (10) in low yields with the de-methoxylated
product methyl 2-(10-methylacridin-9 (10H)-ylidene)acetate ( ) and the reduced compound methyl 2-
7) and
8
methoxy-2-(9H-xanthen-9-yl)acetate (11) as the major products from N-methyl acridone and xanthone.
From thioxanthone, only the rearrangement and reduction products (14) and (15) resulted. The
photophysical properties of compounds (
absence of the Brønsted acid TFA by NMR, UV–VIS absorption, and fluorescence spectroscopy.
Protonation of the acridone-derived alkenes ( ) and ( ) led to strong bathochromic and hyperchromic
fluorescence shifts and a substantial increase in Stokes shift. The photooxygenation experiments
with these substrates showed an unusual reactivity pattern in the singlet oxygen processes: whereas
7), (8), and (10) were investigated in the presence and
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ꢀꢁꢂꢃꢄꢅꢆ
7
8
Citation: Lippold, T.; Neudörfl, J.M.;
Griesbeck, A. New Acridone- and
(Thio)Xanthone-Derived
the electron-rich enolether (
presumably via intermediate 1,2-dioxetanes.
7) was chemically unreactive, (8) and (10) were oxidatively cleaved,
1,1-Donor–Acceptor-Substituted
Alkenes: pH-Dependent Fluorescence
and Unusual Photooxygenation
Properties. Molecules 2021, 26, 3305.
https://doi.org/10.3390/
Keywords: alkenes; acridones; singlet oxygen; fluorescence; Brønsted acid
molecules26113305
Academic Editors: Rui Fausto and
Scott Reed
1. Introduction
There are a very small number of unsaturated organic molecules that can be directly
converted into four-membered cyclic peroxides by reaction with molecular singlet oxy-
gen. These cyclic peroxides, such as 1,2-dioxetanes (
1,2-dioxetan-3,4-dione ( ) (Scheme 1), represent the most potent compound class that can
release bright and intensive light emission that appears in nature and in the laboratory as
bio- and chemiluminescence (CL) [ ]. The biological phenomena are known to mankind
at least since three and a half millennia and can be traced back to ancient writings of
Asian civilizations mentioning “fireflies” and “glow worms” for the first time. The Greek
philosopher Aristotle mentioned the bioluminescence of fungi, and later on, Pliny the
Received: 27 April 2021
Accepted: 24 May 2021
Published: 31 May 2021
1), 1,2-dioxetanones (2), and also
3
1,2
Publisher’s Note: MDPI stays neutral
with regard to jurisdictional claims in
published maps and institutional affil-
iations.
Elder even described bioluminescent clams, jelly, and lantern fishes [3,4]. In 1877, the
Polish chemist Radziszewski realized the first artificial organic chemiluminescence, includ-
ing a cyclic peroxide as the decisive metastable intermediate, from an alkaline solution of
lophine that reacts with molecular oxygen [
and discoveries were made, from the synthesis and characterization of lucigenine [
luminol [ ] to peroxyoxalate chemiluminescence [ 11], which is also used in commercial
glow sticks. Concerning the substituents, the stability and properties of 1,2-dioxetanes can
vary greatly [12 13]. In order to populate the emitting state of the carbonyl product, formed
in the thermal decomposition process, the cleavage of the O O bond represents the first
and rate-limiting step [14 16]. For the unsubstituted 1,2-dioxetane, experimental and theo-
retical investigations resulted in 23.0 and 23.5 kcal mol−1, respectively, for the activation
5
]. Subsequently, more and more publications
Copyright:
© 2021 by the authors.
6] and
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
7,
8
9–
,
−
–
Molecules 2021, 26, 3305. https://doi.org/10.3390/molecules26113305
https://www.mdpi.com/journal/molecules

Molecules 2021, 26, 3305
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energy required for the initial ring opening [17]. Besides this rather high energy barrier
for the cleavage of the O O bond, most uncatalyzed decompositions of 1,2-dioxetanes are
−
proven to have a very poor emission efficiency due to the preferred formation of triplet
excited carbonyl products [18,19].
O O
O O
OCH3
O O
O O
2-
OPO3
R1
R1
R3
O
O
O
R2
R2 R4
1
2
3
AMPPD
OCH3
O O
HO
OCH3
OH
OH
O O
OCH3
O
O
O
HO
O
O
5
4
AMPGD
Scheme 1. Structures of the three basic chemoluminescent peroxides: 1,2-dioxetanes (
dioxetanones ( ), 1,2-dioxetanedione ( ), and the CIEEL-active dioxetanes AMPPD and AMPGD and
(4) with the fluorescent phenolate (5).
1), 1,2-
2
3
Taking into account the effective spin–orbit coupling (SOC), according to El-Sayed’s
rule [20 21], during “entropic trapping” [17], excited triplet states are more stable than
,
excited singlet states, explaining the preferred formation of triplet excited products after
the fragmentation process. With these major problems, it is not surprising that there
is a manageable quantity of efficient CL systems and compounds such as luminol and
lucigenine that are still used in numerous applications of present times as they represent
the optimum of their compound classes. Small changes on efficient possible CL systems
may lead to a major loss of light emission, which immensely increases the difficulty of
the search for new and promising compounds. The first successful thermal preparation
of a 1,2-dioxetane was reported by Kopecky and Mumford, who described the synthesis
of trimethyl-1,2-dioxetane [22,23]. The [2 + 2] cycloaddition of electron-rich olefins with
singlet oxygen, however, is the method of choice for the synthesis of 1,2-dioxetanes. In 1972,
Wieringa et al. published the synthesis of bis-adamantylideneoxetane, the first dioxetane
completely stable at room temperature, via a [2 + 2] cycloaddition with singlet oxygen
and adamantylidene adamantine [24]. This scientific breakthrough enabled new possible
syntheses and modifications of spiroadamantyl-substituted dioxetanes, which were stable
enough to be used for analytical purposes, such as immunoassays and enzyme activity.
Schaap and Bronstein developed 1,2-dioxetanes with adamantyl groups such as AMPPD and
AMPGD (Scheme 1), which could be activated through the use of enzymes or chemically
by releasing the protection group (phosphate, monomeric sugars, etc.) [25–27]. After the
formation of the electronically excited species, either direct chemiluminescence or transfer
of energy to a fluorophore that emits its characteristic fluorescence is observed.
In contrast to the aforementioned thermal decomposition, a different mechanism
for the spiroadamantane-1,2-dioxetanes is the chemically initiated electron exchange lu-
minescence (CIEEL) [
or enzymatic agents, an excellent electron donor in the dioxetane (
intramolecular electron transfer from the phenolate into the O O bond causes cleavage of
this bond with the formation of a biradical anionic species. Finally, the simultaneous back
electron transfer (BET) and C C bond cleavage lead to the loss of adamantanone and the
formation of the phenolate-substituted ester ( ) in its excited singlet state [13 30 32]. The
2,
28,
29]. Initiated through liberation of the phenolate by chemical
4
) is generated. An
−
−
5
, –
return to the singlet ground state is accompanied by emission of a photon (λ = 477 nm) [30].
The proposed CIEEL mechanism represents a recipe for effective chemiluminescence. The
catalytic electron exchange weakens the O O bond, thus decreasing the activation barrier
−

Molecules 2021, 26, 3305
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and generating electronically excited singlet states for potential emission. However, the ex-
act mechanism is still studied when concerning an intra- versus intermolecular BET [13
Additionally, questioning the necessity of a full electron exchange, an alternative mecha-
nism, the charge-transfer-induced luminescence (CTIL), has been proposed [33 35]. Besides
,31].
–
this impressive and intensive research on chemi- and bioluminescence, there is still a de-
mand for better CL systems for analytical and/or application purposes. We have recently
published the first examples of donor–acceptor-substituted alkenes and their reactivity
towards singlet oxygen [36]. The investigations and synthesis of new heterocyclic donor–
acceptor-substituted alkenes as potential systems for chemoselective [2 + 2] cycloadditions
with singlet oxygen are described herein and add a new approach to this complex topic.
2. Results
2.1. Synthesis of Donor–Acceptor Alkenes
The 1,1-donor–acceptor-substituted alkenes were synthesized in one-pot procedures
by applying a synthetic protocol by Krick et al. using a Lehnert-modified Knoevenagel con-
densation [37]. The olefination of 10-methylacridin-9(10H)-one (
methyl 2-methoxyacetate was successful using TiCl4-mediated
condensation with ( ) and ( ), respectively, albeit with low yields and with formation of
by-products ( ) and (11) (Scheme 2). Products ( ) and (10) combine the two relevant fea-
6) and xanthone (
9) with
α
-methoxy methylacetate
6
9
8
7
tures for potential chemiluminescent oxygenation processes: the electron-rich CC double
bond that is reactive in singlet oxygen [2 + 2] cycloadditions and the oxidative cleavage
products, acridone and xanthone, both highly fluorescent ketones. That this substitution
pattern allows efficient dioxetane formation has already been shown for non-heterocyclic
tetrasubstituted alkenes [36]. This synthetic approach delivers the desired target molecules,
unfortunately in low yields, which is due, on the one hand, to moderate conversions
(40%–50% in most cases) and, on the other hand, to the harsh reaction conditions that
lead to two reductive pathways: reductive exchange of the 1-methoxy group by hydrogen
leading to Michael ester product (8) and enone hydrogenation product (11) (and similar
(15) from (12), vide infra).
Scheme 2. Synthesis of the donor–acceptor-alkenes (
7) and (10) from coupling to acridone and
xanthone with two unexpected side products, (8) and (11).
Applying the same synthesis protocol to thioxanthone (12) as starting material did
not give the expected olefin (13) at all, but a mixture of the aldehyde (14) and the reduced
derivative (15) (Scheme 3). The structurally unusual product (14) and the alkene (15) could
also be analyzed by X-ray crystal structure determination (see SI).
While the formation of (15) corresponds to an analogous reduction process as for (11),
the formation and addition of the oxoethyl substituent of (14) seems cumbersome (but
reproducible) and cannot be explained yet. In order to investigate whether a different
amine base leads to different results, triethylamine (TEA) was exchanged by diisopropy-
lethylamine (DIPEA). While the same products were obtained, their respective yields were

Molecules 2021, 26, 3305
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higher, allowing a more efficient synthesis for these two compounds (14
/
15: 16% and 23%
with TEA; 20% and 29% with DIPEA). In the case of the reaction with 10-methylacridin-
9(10H)-one (6), the two alkenes (7) and (8) were obtained.
Scheme 3. Conversion of the thioxanthone (12) into the double alkylation product (14) and the
reduction product (15); structure of the aldehyde (14) in the crystal.
In the case of the reaction with 10-methylacridin-9(10H)-one (
and ( ) were obtained. Here, a side reaction seems to occur, where the methoxy group of
the -carbon was reduced to a CH group, leading to the formation of the acridinylidene
acetate. When comparing the results with those of Krick and Lehnert, who used rather
strong -acidic compounds, it appears that a reduction mechanism takes place in the
reactions with weaker acids [37 41]. The deprotonation of methyl 2-methoxyacetate may
6), the two olefins (7)
8
α
α
–
also proceed slower and thus allows side reactions to occur. In all cases, the nitrogen base
trimethylamine serves as the hydrogen donor in these reductive processes, which is also in
agreement with the effect of base exchange, where better yields of these reduction products
were obtained in the presence of DIPEA instead of TEA.
2.2. Fluorescence and UV–VIS Absorption Properties
The newly synthesized alkenes (7), (8), and (10) were characterized by fluorescence
and UV–VIS spectroscopy (Figure 1 and Table 1, highlighted in yellow). Table 1 shows
that these compounds are similar when comparing the absorption coefficients with system
(
7
) having the lowest absorbance. While the xanthenylidene derivative (10) absorbs in
the UV-A range with 329 nm, the absorption maxima of both acridinylidene derivatives
) and ( ) are shifted towards higher wavelengths of 378 and 417 nm, respectively. Of
all three systems, only ( ) and ( ) show low fluorescence emission. The spectrum of (
itself shows two distinguishable maxima at 410 and 432 nm. Even though the absorption
) and ( ) can be seen at 378 and 417 nm, respectively,
(
7
8
7
8
8)
maxima of the n → π* transitions of (
7
8
an excitation wavelength of 360 nm was chosen for the fluorescence spectra, which allowed
the measurement of a spectrum where the complete curve progression was visible.
Table 1. Low-energy (red-shifted) absorption wavelengths (λabsmax), corresponding absorption
coefficients (
yields ΦF of (
are from the experiments without acid added.
ε
), excitation wavelengths (
λ
ex), emission maxima (λemmax), and fluorescence quantum
7
), ( ), and (10) without ( ) and with (+) 500 eq. of TFA. The data highlighted in yellow
8
−
Absorption
λem
Quantum
λabs
max
max
Compound
TFA
Coefficient ελ
(L/mol·cm)
9370
λex (nm)
(nm)
Yield Φ
(nm)
F
−
+
378
366
417
362
329
329
360
366
360
362
329
329
398
511
0.008
0.310
0.035
0.886
−
7
8
11,580
12,540
22,890
13,520
−
410/432
476/495
−
+
−
+
10
12,040
−
−

Molecules 2021, 26, 3305
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Figure 1. Absorption (
a
) and fluorescence (
c) spectra of compounds (7) (blue), (8) (green), and (10)
(red) in the absence of TFAin MeCN; absorption (
500 eq. of TFA. Standardized compound concentration of 10 mol/L in MeCN.
b
) and fluorescence (
d
) spectra after the addition of
−5
Krick et al. performed TFA experiments with their acridinylidene systems and ob-
served a proton-induced fluorescence [37]. Therefore, the heteroaromatic compounds (
), and (10) were also measured in the presence 500 eq. of TFA to investigate whether a
protonation occurs and how it influences the photophysical properties (Figure 1, Table 1).
The absorption maxima of ( ) and ( ) were shifted towards shorter wavelengths, while the
7),
(
8
7
8
absorption spectrum of the xanthenylidene derivative (10) remained the same. Additional
measurements in the presence of trifluoroacetic acid (TFA) were performed in order to
gain information on the electronic structure of the conjugated
fluorescence and absorption changes with protonation effects.
π-system and to correlate
Every compound was measured with an identical concentration of c = 10−5 mol/L
in acetonitrile to determine the absorption (λabs) and emission (
λem) wavelength maxima,
fluorescence quantum yields
Φ
F, and respective absorption coefficients ελ. The fluorescence
quantum yields ΦF were determined comparatively using quinine hemisulfate in 0.1 M
sulfuric acid as a reference substance [42].
The addition of TFA shifts the absorption maxima for (7) and (8) to 366 and 362 nm,
respectively, with additional blue-shifted maxima at 261 and 260 nm (Figure 1b). This
suggests the possible formation of an acridinium cation, whose characteristic absorption
maxima are at 260 nm and in the region of 300–500 nm [43
fluorescence, at 476 and 495 nm, can be seen in the curve progression of (
,
44]. Again, two maxima for the
) (Figure 1d).
) are in agreement with the reported emission
= 490 nm) [45], compound ( ) shows a red-
8
While the emission wavelength values of (
8
maximum for N-methylacridinium (λem
7
max
shifted emission at 511 nm. Comparing the fluorescence intensities of the three substrates,
compound (10) does not seem to react/interact with TFA so that under acidic conditions, the
photophysical properties do not change. Acridinylidene systems (7) and especially (8) both
show an increase in fluorescence characteristics after protonation with TFA (Figure 1d). The
same observation was made when comparing the quantum yields. While the unprotonated
substrates have weak or no fluorescence, a 30- to 40-fold increase in the quantum yields
results from the addition of TFA (Table 1). For further investigation, 10 mg of each of
acridinylidene derivatives (7) and (8) were dissolved in 1 mL CDCl3. Subsequently, 50 eq. of

Molecules 2021, 26, 3305
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TFA was added to ensure a quantitative protonation, and 2D-NMR spectra were measured
(1H-NMR: 500 MHz, 13C-NMR: 125 MHz) to determine the structure of the corresponding
protonated species. Figure 2 shows the spectrum of compound (7) before and after the
protonation. The two most significant changes are the new signals at 4.92 ppm with an
integral of 3 protons (N-methyl group) and at 6.50 ppm with an integral of 1 proton (CH
group of the geminal ether/ester moiety). Besides that, it can be seen that the proton
signals in the aromatic region are shifted towards higher ppm values.
Figure 2. Left: solutions of acridinylidenes (
7) and (8) (from left to right) in the presence of 500 eq.
of TFA in MeCN. The samples were excited with an UV lamp (
λ
= 366 nm); right: acridinylidene
em
(top) 1H-NMR of (
7) without and (bottom) with 50 eq. of TFA. Two new significant signals at 4.92
(N-methyl group) and 6.50 ppm (strongly deshielded CH group) appear.
Through the additional information of the 2D-NMR spectra, it could be proven that
the protonation takes place at the carbon atom with the germinal ether/ester system and
the acridinium cation (7-H+) is formed. This is in agreement with the results from a study
by Krick et al. [18]. The NMR-measurements of (8) with 50 eq. TFA gave the same result
(Figure 2). Comparing the 1H-NMR spectra before and after the protonation, a stronger
deshielding effect in the aromatic region occurs. The spin systems consist of doublets
and triplets, indicating that the aromatic protons became indistinguishable and formed
a symmetric unit after the protonation. It is noteworthy that a CH2 fragment appears at
5.11 ppm and already hints that protonation occurred at the carbon atom of the olefin
with the ester substituent. Again, with the investigation of all 2D-NMR spectra, it was
proven that the acridinium cation (8-H+) was formed. Therefore, both systems show to
be preferentially protonated at the
formation of the acridinium cation increases the fluorescence intensity, especially in the
case of compound (
). Comparing (8-H+) with the N-methyl acridinium cation of (7-H+),
α-carbon of the acceptor–donor moiety. The resulting
8
both values of the quantum yield and fluorescence intensity are remarkably higher.
2.3. Photooxygenation of the Geminal Acceptor–Donor Systems
The three alkenes (
gen. Even though ( ) does not represent an acceptor–donor system, it was also investigated
to have a system comparable to ( ). Every reaction was performed in an NMR tube with
TPP as the photosensitizer (0.1 mg, c = 1.63
10−4 mol/L) in 1 mL of CDCl3. In general,
7), (8), and (10) were oxygenated with photosensitized singlet oxy-
8
7
×
20 mg of the respective compounds were used. The reaction progress was monitored via
1H-NMR after constant time intervals.
The photooxygenation of the xanthenylidene derivative (10) shows a decomposition
reaction to the corresponding carbonyl compounds xanthone (7.39, 7.51, 7.74, and 8.35 ppm)
and dimethyloxalate (3.92 ppm), suggesting a [2 + 2] cycloaddition with singlet oxygen
(Figure 3). Comparing the integrals of dimethyloxalate with the signals of the methyl
groups of the substrate (3.59 and 3.74 ppm) gives a distribution of 38% carbonyl products
and 62% starting material after a reaction time of 1 h. The photooxygenation was performed
for 6 h, but after 2.5–3 h, the decomposition was already quantitative.

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Figure 3. NMR time traces of photooxygenation experiment: xanthone-derived substrate (10) (left);
acridone-derived substrate (8) (right). Blue boxes = increase of signal intensity; red boxes = decrease
of signal intensity.
The photooxygenation of other acridinylidene derivatives has already been proven
to be a viable option for clearly visible chemiluminescence [46]. Investigation of the
reactivity of the acridinylidene derivatives (
7
) and (
8
) towards singlet oxygen is therefore
) only has
an interesting topic. While ( ) possesses a geminal acceptor–donor structure, (
7
8
an electron-withdrawing ester group that is expected to deactivate the carbon–carbon
double bond in its reaction with singlet oxygen.
Surprisingly, the methyl-protected acridinylidene derivative (
singlet oxygen within the standard reaction time of 12 h (Scheme 4). The 1H-monitored
photooxygenation of ( ) is depicted in Figure 3, showing a quantitative decomposition
to the corresponding carbonyl product N-methylacridone ( ) with significant signals at
7) did not react with
8
6
3.92, 7.31, 7.55, 7,74, and 8.58 ppm. The corresponding second cleavage product methyl
2-oxoacetate could not be detected in the NMR [47]. According to the literature, this
compound easily polymerizes in solution [48].
Summarizing all photooxygenation experiments, three significant observations were
made: (a) The 1,1-donor–acceptor-substituted alkene (10) behaves as expected for an
electron-rich substrate without allylic hydrogens [36]. The formation of the carbonyl
1
cleavage products indicates an initial [2 + 2] cycloaddition with O2 and subsequent
cycloreversion of the dioxetane (17). (b) A similar reactivity was observed for the Michael
substrate (8), which indicates that the lack of the electron-donating enolether group is
compensated in part by the nitrogen-containing heterocycle that serves as an additional
electron-donating group (as becomes also visible in the protonation experiments. (c) From
observations (a) and (b), the conclusion is obvious that (7) must be the most reactive
substrates because it combines enol ether and the tertiary amino group. This was not
observed experimentally, quite the contrary. One explanation might be that conclusion (c)
is nevertheless correct, but (
7) serves as a strong physical singlet oxygen quencher as also
known for other tertiary amines [49].

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Scheme 4. Photooxygenation of the acridone- and xanthone-derived alkenes (
7), (
8), and (10) and
proposed 1,2-dioxetane intermediates (16) and (17).
3. Materials and Methods
All reagents and solvents were purchased from commercial sources. The degree
of purity of the compounds was at least 95%, and they were used without any further
treatment. DCM was refluxed over calcium hydride under argon atmosphere and freshly
1
distilled prior to use. H- and 13C-NMR spectra were recorded at 300 or 500 MHz and 75 or
125 MHz, respectively. The measurements were performed on a Bruker Avance III 500 MHz
and on a Bruker Avance II 300 MHz (Bruker, Ettlingen, Germany). The chemical shifts
are reported in ppm downfield of the internal standard of TMS [
(1H-NMR) = 0.00 ppm
(13C-NMR) = 0.00 ppm]. CDCl3 [ (1H-NMR) = 7.24 ppm, (13C-NMR) = 77.2 ppm]
δ
δ
,
δ
δ
δ
was used as the solvent. The coupling constant J is indicated in Hz. The fine structure
is designated using the following abbreviations: s (singlet), d (doublet), t (triplet), q
(quartet), quin (quintet), sxt (sextet), br (broad), and m (multiplet). Infrared spectra were
measured with a Nicolet 380 FTIR (Thermo Fischer Scientific, Waltham, MA, USA). The
wave numbers are categorized from 4000 to 800 cm−1. The signals are listed with the
following abbreviations: w (weak), m (medium), s (strong), vs (very strong), and br (broad
signal). The melting points of solid compounds were determined with a Melting Point
apparatus B-545 (Büchi Labortechnik, Essen, Germany). Absorption spectra were measured
with a UV–VIS spectrometer Type Lambda 35 (PerkinElmer, Waltham, MA, USA). Every
sample was measured in quartz absorption cells with a diameter of 1 cm. Fluorescence
spectra were measured with a luminescence spectrometer, LS-55B (PerkinElmer). Quartz
fluorescence cells with a diameter of 1 cm were used for the measurements. High-resolution
mass spectra were measured with a MAT 900 S and with an LTQ Orbitrap XL (Thermo
Fischer Scientific, Waltham, MA, USA) via electrospray ionization (ESI). Crystal structure
analyses were performed on a Nonius KappaCCD-Circle diffractometer. The structure was
resolved using SHELXS-97 and SHELXL-97. Flash chromatography was performed on
silica gel 60 Å, particle size 0.035–0.070 mm (Macherey-Nagel, Düren, Germany).
General procedure for olefination: In a double-heated three-necked flask with a reflux
condenser and septum, TiCl4 (1.25 eq.) was slowly added under argon atmosphere to the
ketone compound (1.00 eq.) dissolved in dry CH2Cl2 (15 mL per mmol ketone compound).
The mixture was stirred for 15 min at room temperature. Methyl 2-methoxyacetate (2.00 eq.)
and triethylamine or DIPEA (13.5 eq.) were added consecutively to the reaction mixture,
which was subsequently heated under reflux for 24 h. An aqueous solution of HCl (1M) was
added to the cooled-down reaction mixture until a clear solution emerged and extracted
three times with CH2Cl2. The combined organic phases were washed with brine, dried

Molecules 2021, 26, 3305
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over either MgSO4 or Na2SO4, and filtered, and the solvent was removed in vacuo. The
residue was purified via column chromatography on SiO2.
General procedure for photooxygenation: In a NMR tube, the olefin (20 mg) was
dissolved in CDCl3 (1 mL). An amount of 0.1 mg of TPP (c = 1.63
×
10−4 mol/L) was
added, and the solution was saturated wi◦th oxygen over an inlet under light irradiation
with two halogen lamps (150 W each) at 25 C. The reaction progress was monitored via 1H-
NMR after certain periods of time. After the reaction was completed, the product/products
were not worked up or purified.
Methyl 2-methoxy-2-(10-methylacridin-9(10H)-ylidene)acetate (7) and methyl 2-(10-
methylacridin-9(10H)-ylidene)acetate (8)
They were prepared according to the general procedure for olefinations, using 10-
methylacridin-9(10H)-one (6) (1.00 g, 4.78 mmol, 1.00 eq.), methyl 2-methoxyacetate (0.95 mL,
9.56 mmol, 2.00 eq.), triethylamine (8.90 mL, 64.5 mmol, 13.5 eq.), TiCl4 (0.65 mL, 5.98 mmol,
1.25 eq.) in DCM (60 mL). The crude products were purified by flash column chromatogra-
phy with n-hexane/EtOAc (18:1). Products (
oil with a yield of 0.04 g (0.14 mmol, 3%) and 0.12 g (0.43 mmol, 9%) respectively.
Analytical data for
: Rf = 0.36 (5:1, n-Hex/EtOAc). 1H-NMR (500 MHz, CDCl3,
298 K): [ppm] = 3.49 (s, 3H), 3.50 (s, 3H), 3.68 (s, 3H), 6.95 (td, J = 7.4 and 1.0 Hz, 1H),
7.01 (m, 1H), 7.03 (m, 1H), 7.05 (m, 1H), 7.23 (dd, J = 7.8 and 1.5 Hz, 1H), 7.30 (m, 2H),
8.13 (dd, J = 7.9 and 1.6 Hz, 1H). 13C-NMR (125 MHz, CDCl3, 298 K):
[ppm] = 33.6 (CH3),
7) and (8) were both obtained as a green viscous
7
δ
δ
51.5 (CH3), 57.7 (CH3), 112.0 (CHarom), 112.3 (CHarom), 120.3 (CHarom), 120.4 (CHarom),
121.2 (Cq), 121.4 (Cq), 123.0 (Cq), 127.4 (CHarom), 128.3 (CHarom), 128.6 (CHarom), 128.7
(CHarom), 139.1 (Cq), 141.7 (Cq), 142.1 (Cq), 166.4 (Cq). IR (FTIR):
ῦ
[cm−1] = 2943 (w),
2833 (w), 2361 (w), 1712 (s), 1592 (m), 1496 (w), 1463 (vs), 1431 (w), 1351 (m), 1333 (w), 1257
(vs), 1217 (m), 1190 (w), 1168 (w), 1152 (w), 1132 (w), 1115 (m), 1063 (w), 1051 (w), 1024 (w),
940 (w), 962 (w), 911 (w), 888 (w), 858 (w), 806 (w). HRMS (ESI): calcd. [M + H]+: 296.12811,
found: 296.12873; calcd. [M + Na]+: 318.11006, found: 318.11049.
Analytical data for
298 K): [ppm] = 3.59 (s, 3H), 3.73 (s, 3H), 6.00 (s, 1H), 7.08 (m, 1H), 7.10 (m, 1H), 7.13 (m,
1H), 7.16 (m, 1H), 7.42 (m, 1H), 7.44 (m, 1H), 7.75 (dd, J = 7.9 and 1.5 Hz, 1H), 7.95 (dd, J
= 7.9 and 1.5 Hz). 13C-NMR (125 MHz, CDCl3, 298 K):
[ppm] = 34.0 (CH3), 51.1 (CH3),
8
: Rf = 0.27 (5:1, n-Hex/EtOAc). 1H-NMR (500 MHz, CDCl3,
δ
δ
108.6 (CH), 112.9 (CHarom), 113.1 (CHarom), 119.5 (CHarom), 119.9 (Carom), 121.4 (Carom),
124.0 (Cq), 124.2 (CHarom), 129.8 (CHarom), 130.3 (CHarom), 130.6 (CHarom), 140.1 (Cq), 141.4
(Cq), 145.3 (Cq), 167.6 (Cq). IR (FTIR):
ῦ
[cm−1] = 2946 (w), 1703 (m), 1591 (s), 1487 (w), 1462
(vs), 1431 (w), 1356 (w), 1301 (w), 1269 (w), 1156 (vs), 1130 (vs), 1060 (w), 1049 (w), 971 (w),
938 (w), 888 (w), 856 (w). HRMS (ESI): calcd. [M + H]+: 266.11756, found: 266.11771; calcd.
[M + Na]+: 282.11247, found: 282.11268.
Methyl 2-methoxy-2-(9H-xanthen-9-ylidene)acetate (10) and methyl 2-methoxy-2-
(9H-xanthen-9-yl)acetate (11)
They were prepared according to the general procedure for olefinations, using xan-
thone (9) (0.94 g, 4.80 mmol, 1.00 eq.), methyl 2-methoxyacetate (1.00 mL, 9.61 mmol,
2.00 eq.), triethylamine (9.00 mL, 64.8 mmol, 13.5 eq.), TiCl4 (0.66 mL, 6.00 mmol, 1.25 eq.)
in DCM (60 mL). The crude products were purified by flash column chromatography
with c-hexane/EtOAc (20:1
→
10:1). Both separated products were then freed of remaining
◦
xanthone via Kugelrohr distillation (165 C, 5.7 mbar). Product (10) was obtained as a
yellow solid and (11) as a yellow viscous oil with yields of 0.08 g (0.28 mmol, 6%) and
0.20 g (0.70 mmol, 15%), respectively.
1
Analytical data for 10: Rf = 0.18 (20:1, c-Hex/EtOAc). H-NMR (500 MHz, CDCl3,
298 K):
1H), 7.19 (m, 2H), 7.21 (m, 1H), 7.30 (m, 2H), 8.15 (dd, J = 8.0 and 1.6 Hz, 1H). 13C-NMR
(125 MHz, CDCl3, 298 K): [ppm] = 51.9 (CH3), 57.6 (CH3), 116.2 (CHarom), 116.5 (CHarom),
δ [ppm] = 3.59 (s, 3H), 3.74 (s, 3H), 7.05 (ddd, J = 7.9, 7.2, and 1.3 Hz, 1H), 7.15 (m,
δ
117.1 (Cq), 121.0 (Cq), 121.4 (Cq), 122.8 (CHarom), 123.1 (CHarom), 126.7 (CHarom), 128.7
(CHarom), 128.9 (CHarom), 129.1 (CHarom), 140.9 (Cq), 152.3 (Cq), 152.6 (Cq), 165.9 (Cq). IR
(FTIR):
ῦ
[cm−1] = 2942 (w), 1716 (vs), 1656 (w), 1597 (w), 1581 (w), 1476 (m), 1450 (vs),

Molecules 2021, 26, 3305
10 of 13
1337 (m), 1252 (vs), 1226 (vs), 1208 (s), 1161 (m), 1128 (s), 1109 (s), 1101 (s), 1043 (m), 1022 (s),
962 (w), 940 (w), 914 (w), 898 (w), 881 (w), 864 (w), 816 (w). M.p.: 72–75 ◦C.
HRMS (ESI): calcd. [M + H]+: 283.09648, found: 283.09679; calcd. [M + Na]+: 305.07843,
found: 305.07868.
1
Analytical data for 11: Rf = 0.07 (20:1, c-Hex/EtOAc). H-NMR (500 MHz, CDCl3,
298 K):
δ [ppm] = 3.21 (s, 3H), 3.60 (s, 3H), 3.83 (d, J = 5.6 Hz, 1H), 4.40 (d, J = 5.6 Hz,
1H), 7.07 (tt, J = 7.5 and 1.7 Hz, 2H), 7.11 (d, J = 7.9 Hz, 1H), 7.12 (d, J = 7.9 Hz, 1H), 7.22
(dd, J = 7.6 and 1.4 Hz, 1H), 7.24 (m, 1H), 7.26 (m, 1H), 7.28 (m, 1H). 13C-NMR (125 MHz,
CDCl3, 298 K):
116.5 (CHarom), 120.8 (Cq), 121.0 (Cq), 123.0 (CHarom), 123.2 (CHarom), 128.4 (CHarom), 128.5
(CHarom), 128.8 (CHarom), 129.4 (CHarom), 152.8 (Cq), 153.0 (Cq), 171.2 (Cq). IR (FTIR):
δ [ppm] = 43.1 (CH), 51.8 (CH3), 59.0 (CH3), 86.5 (CH), 116.4 (CHarom),
ῦ
[cm−1] = 2949 (w), 2831 (w), 1748 (m), 1651 (w), 1601 (w), 1577 (w), 1458 (s), 1355 (w),
1301 (w), 1254 (vs), 1201 (m), 1154 (w), 1118 (s), 1027 (w), 1003 (w), 963 (w), 942 (w), 927
(w), 893 (w), 861 (w), 830 (w). HRMS (ESI): calcd. [M + Na]+: 307.09408, found: 307.09427.
Methyl 2-methoxy-2-(9-(2-oxoethyl)-9H-thioxanthen-9-yl)acetate (14) and methyl 2-
methoxy-2-(9H-thioxanthen-9-yl)acetate (15)
They were prepared according to the general procedure for olefinations, using thiox-
anthone (12) (1.00 g, 4.71 mmol, 1.00 eq.), methyl 2-methoxyacetate (0.93 mL, 9.42 mmol,
2.00 eq.), DIPEA (10.8 mL, 63.6 mmol, 13.5 eq.), TiCl4 (0.65 mL, 5.89 mmol, 1.25 eq.) in
DCM (60 mL). The crude products were purified by flash column chromatography with
n-hexane/EtOAc (4:1). Product (14) was obtained as a colorless solid with a camphor-
like smell and (15) as an orange solid with yields of 0.32 g (0.93 mmol, 20%) and 0.41 g
(0.43 mmol, 29%), respectively.
Analytical data for 14: Rf = 0.23 (4:1, n-Hex/EtOAc). 1H-NMR (500 MHz, CDCl3,
298 K):
δ [ppm] = 2.99 (s, 3H), 3.27 (s, 3H), 3.71 (dd, J = 19.7 and 2.3 Hz, 1H), 3.97 (dd,
J = 19.7 and 1.9 Hz), 4.48 (s, 1H), 7.19 (m, 1H), 7.22 (m, 1H), 7.26 (m, 1H), 7.29 (m, 1H),
7.30 (m, 1H), 7.41 (m, 1H), 7.48 (m, 2H), 9.61 (t, J = 2.0 Hz, 1H). 13C-NMR (125 MHz,
CDCl3, 298 K):
δ [ppm] = 40.5 (CH2), 48.9 (Cq), 51.6 (CH3), 58.9 (CH3), 78.5 (CH), 126.5
(CHarom), 126.6 (CHarom), 127.1 (CHarom), 127.2 (CHarom), 127.3 (CHarom), 127.4 (CHarom),
127.7 (CHarom), 128.9 (CHarom), 131.9 (Cq), 133.1 (Cq), 133.3 (Cq), 134.4 (Cq), 170.6 (Cq),
202.1 (Caldehyde). IR (FTIR):
ῦ
[cm−1] = 3583 (w), 3564 (w), 3445 (w), 2924 (w), 2852 (w),
2360 (w), 2343 (w), 1738 (vs), 1717 (vs), 1464 (m), 1445 (w), 1425 (w), 1362 (w), 1311 (w),
1301 (w), 1272 (w), 1219 (m), 1197 (s), 1176 (w), 1113 (s), 1064 (w), 1051 (w), 1012 (w), 956
(m), 945 (w), 913 (w), 811 (w). M.p.: 131.4 ◦C. HRMS (ESI): calcd. [M + H]+: 343.09985,
found: 343.09992; calcd. [M + Na]+: 365.08180, found: 365.08170.
Analytical data for 15: Rf = 0.36 (4:1, n-Hex/EtOAc). 1H-NMR (500 MHz, CDCl3,
298 K):
7.17 (m, 1H), 7.19 (m, 1H), 7.21 (m, 1H), 7.23 (m, 1H), 7.25 (m, 1H), 7.40 (m, 1H), 7.42 (m,
2H). 13C-NMR (125 MHz, CDCl3, 298 K):
[ppm] = 51.6 (CH3), 52.6 (CH), 58.6 (CH3), 79.0
δ [ppm] = 3.10 (s, 3H), 3.42 (s, 3H), 4.13 (d, J = 9.7 Hz, 1H), 4.36 (d, J = 9.6 Hz, 1H),
δ
(CH), 126.3 (CHarom), 126.4 (CHarom), 126.6 (CHarom), 126.9 (CHarom), 127.2 (CHarom), 127.4
(CHarom), 129.4 (CHarom), 131.3 (CHarom), 132.2 (Cq), 132.8 (Cq), 133.4 (Cq), 134.1 (Cq), 171.8
(Cq). IR (FTIR):
ῦ
[cm−1] = 3059 (w), 2996 (w), 2934 (w), 2832 (w), 2359 (w), 2343 (w), 1744
(vs), 1585 (w), 1465 (m), 1445 (m), 1430 (w), 1365 (w), 1313 (w), 1295 (w), 1277 (w), 1243
(w), 1227 (w), 1203 (s), 1176 (m), 1151 (w), 1113 (s), 1078 (w), 1065 (w), 1041 (w), 1030 (w),
1007 (m), 982 (w), 961 (w), 947 (w), 928 (w), 887 (w), 873 (w), 860 (w), 830 (w). HRMS (ESI):
calcd. [M + Na]+: 323.07123, found: 323.07155.
Photooxygenation of methyl 2-(10-methylacridin-9(10H)-ylidene)acetate (8).
The reaction was performed according to the general procedure for photooxygenation
using (
8
) (20 mg, 0.07 mmol, 1.00 eq.) and TPP (1.0 mg, c = 1.63
×
10−4 mol/L) dissolved in
CDCl3 (1 mL). After 12 h, the reaction was completed, and 10-methoxyacridin-9(10H)-one
(19) and an unidentifiable compound were obtained.
Photooxygenation of methyl 2-methoxy-2-(9H-xanthen-9-ylidene)acetate (10)
The reaction was performed according to the general procedure for photooxygenation
using (10) (20 mg, 0.07 mmol, 1.00 eq.) and TPP (1.0 mg, c = 1.63
×
10−4 mol/L) dissolved in

Molecules 2021, 26, 3305
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CDCl3 (1 mL). After 6 h, the reaction was completed, and xanthone (
were obtained.
9) and dimethyloxalate
4. Conclusions
Two new heterocyclic donor–acceptor-substituted alkenes (
sized via Knoevenagel condensation from 10-methylacridin-9(10H)-one (
) with titanium (IV) chloride. An additional acceptor-substituted compound (
does not represent an acceptor–donor system was also included in the photooxygenation
study. The results of the singlet oxygen reactions showed that ( ) and (10) are versatile
substrates for singlet oxygen [2 + 2] cycloaddition reactions, whereas ( ) surprisingly does
not show chemical quenching abilities, possibly an effect of a strong physical quenching of
singlet oxygen by the tertiary amine ( ). Concerning their photophysics, the heteroaromatic
compounds ( ) and ( ) were only slightly fluorescent and (10) showed no fluorescence at
all. After the addition of 500 eq. of TFA, however, a strong increase in fluorescence intensity
was detected for ( ) and ( ), while the xanthenylidene derivative (10) did not change in
7
) and (10) were synthe-
) and xanthone
) that
6
(
9
8
8
7
7
7
8
7
8
fluorescence. NMR analyses revealed the formation of the corresponding acridinium cation
structures (7H+) and (8H+).
Supplementary Materials: The following are available online: NMR and IR spectra of compounds
(7), (8), (10), (11), (14), and (15); X-ray data of compounds (14) and (15) [50].
Author Contributions: Conceptualization, A.G.; X-ray analysis and data curation, J.M.N.; writing—
original draft preparation, T.L. and A.G.; research, T.L.; supervision, A.G. All authors have read and
agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: Not applicable.
Informed Consent Statement: Not applicable.
Data Availability Statement: Data are contained within the article or Supplementary Material.
Conflicts of Interest: The authors declare no conflict of interest.
References
1.
2.
3.
Shimomura, O.; Goto, T.; Johnson, F.H. Source of oxygen in the CO2 produced in the bioluminescent oxidation of firefly luciferin.
Proc. Natl. Acad. Sci. USA 1977, 7, 2799–2802. [CrossRef] [PubMed]
Koo, J.-Y.; Schuster, G.B. Chemically initiated electron exchange luminescence. A new chemiluminescent reaction path for organic
peroxides. J. Am. Chem. Soc. 1977, 99, 6107–6109. [CrossRef]
Harvey, E.N. A History of Luminescence, from the Earliest Times until 1900; Memoirs of the American Philosophical Society; The
American Philosophical Society: Philadelphia, USA, 1957; p. 44.
4.
5.
6.
7.
8.
Albrecht, S.; Brandl, H.; Zimmermann, T. Chemilumineszenz; Hüthig Verlag: Heidelberg, Germany, 1996.
Radziszewski, B. Untersuchungen über Hydrobenzamid, Amarin und Lophin. Ber. Dtsch. Chem. Ges. 1877, 10, 70–75. [CrossRef]
Gleu, K.; Petsch, W. Die Chemiluminescenz der Dimethyldiacridyliumsalze. Angew. Chem. 1935, 48, 57–72. [CrossRef]
Albrecht, H.O. Über die Chemiluminescenz des Aminophthalsäurehydrazids. Z. Phys. Chem. 1928, 136, 321–330. [CrossRef]
Mayer, M.; Takegami, S.; Neumeier, M.; Rink, S.; Jacobi von Wangelin, A.; Schulte, S.; Vollmer, M.; Griesbeck, A.G.; Duerkop, A.;
Bäumner, J. Electrochemiluminescence Bioassays with a Water-Soluble Luminol Derivative Can Outperform Fluorescence Assays.
Angew. Chem. Int. Ed. 2018, 57, 408–411. [CrossRef]
9.
Griesbeck, A.G.; Diaz-Miara, Y.; Jacobi von Wangelin, A.; Pérez-Ruiz, R.; Sampredo, D. Steric Enhancement of the Chemilumines-
cence of Luminols. Chem. Eur. J. 2015, 21, 9975–9979. [CrossRef] [PubMed]
10. Chandross, E.A. A new chemiluminescent system. Tetrahedron Lett. 1963, 12, 761–765.
11. Ciscato, L.F.M.L.; Bartoloni, F.H.; Bastos, E.L.; Baader, W.J. Direct Kinetic Observation of the Chemiexcitation Step in Peroxyoxalate
Chemiluminescence. J. Org. Chem. 2009, 74, 8974–8979. [CrossRef] [PubMed]
12. Ciscato, L.F.M.L.; Augusto, F.A.; Weiss, D.; Bartoloni, F.H.; Albrecht, S.; Brandl, H.; Zimmermann, T.; Baader, W.J. The chemilumi-
nescent peroxyoxalate system: State of the art almost 50 years from its discovery. ARKIVOC 2012, 2012, 391–430. [CrossRef]
13. Vacher, M.; Galván, I.F.; Ding, B.-W.; Schramm, S.; Berraud-Pache, R.; Naumov, P.; Ferré, N.; Liu, Y.-J.; Navizet, I.; Roca-Sanjuán,
D.; et al. Chemi- and Bioluminescence of Cyclic Peroxides. Chem. Rev. 2018, 118, 6927–6974. [CrossRef] [PubMed]
14. Farahani, P.; Roca-Sanjuán, D.; Zapata, F.; Lindh, R. Revisiting the Nonadiabatic Process in 1,2-Dioxetane. J. Chem. Theory Comput.
2013, 9, 5404–5411. [CrossRef]

Molecules 2021, 26, 3305
12 of 13
15. Tanaka, C.; Tanaka, J. Ab Initio Molecular Orbital Studies on the Chemiluminescence of 1,2-Dioxetanes. J. Phys. Chem. A 2000
104, 2078–2090. [CrossRef]
,
16. Rodríguez, E.; Reguero, M. The DDCI Method Applied to Reactivity: Chemiluminescent Decomposition of Dioxetane. J. Phys.
Chem. A 2002, 106, 504–509. [CrossRef]
17. De Vico, L.; Liu, Y.-J.; Krogh, J.W.; Lindh, R. Chemiluminescence of 1,2-Dioxetane. Reaction Mechanism Uncovered. J. Phys. Chem.
A 2007, 111, 8013–8019. [CrossRef] [PubMed]
18. Baader, W.J.; Stevani, C.V.; Bastos, E.L. The Chemistry of Peroxides; Rappoport, Z., Ed.; John Wiley & Sons, Ltd.: Hoboken, NJ, USA,
2006; pp. 1211–1278.
19. Adam, W. Chemical and Biological Generation of Excited States; Adam, W., Cilento, G., Eds.; Academic Press: Cambridge, MA, USA,
1982; pp. 1115–1152.
20. El-Sayed, M.A. Spin—Orbit Coupling and the Radiationless Processes in Nitrogen Heterocyclics. J. Chem. Phys. 1963, 38,
2834–2838. [CrossRef]
21. El-Sayed, M.A. Triplet state. Its radiative and nonradiative properties. Acc. Chem. Res. 1968, 1, 8–16. [CrossRef]
22. Kopecky, K.R.; van de Sande, J.H.; Mumford, C. Preparation and base-catalyzed reactions of some β-halohydroperoxides. Can. J.
Chem. 1968, 46, 25–34. [CrossRef]
23. Kopecky, K.R.; Mumford, C. Luminescence in the thermal decomposition of 3,3,4-trimethyl-1,2-dioxetane. Can. J. Chem. 1969, 47,
709–711. [CrossRef]
24. Wieringa, J.H.; Strating, J.; Wynberg, H.; Adam, W. Adamantylideneadamantane peroxide, a stable 1,2-dioxetane. Tetrahedron Lett.
1972, 2, 169–172. [CrossRef]
25. Bronstein, I.; McGrath, P. Chemiluminescence lights up. Nature 1989, 338, 599–600. [CrossRef] [PubMed]
26. Bronstein, I.; Edwards, B.; Voyta, J.C. 1,2-Dioxetanes: Novel chemiluminescent enzyme substrates. Applications to immunoassays.
J. Biolumin. Chemilumin. 1989, 4, 99–111. [CrossRef]
27. Schaap, A.P.; Akhavan, H.; Romano, L. Chemiluminescent substrates for alkaline phosphatase: Application to ultrasensitive
enzyme-linked immunoassays and DNA probes. Clin. Chem. 1989, 35, 1863–1864. [CrossRef] [PubMed]
28. Koo, J.A.; Schmidt, S.P.; Schuster, G.B. Bioluminescence of the firefly: Key steps in the formation of the electronically excited state
for model systems. Proc. Natl. Acad. Sci. USA 1978, 75, 30–33. [CrossRef] [PubMed]
29. Koo, J.-Y.; Schuster, G.B. Chemiluminescence of diphenoyl peroxide. Chemically initiated electron exchange luminescence. A new
general mechanism for chemical production of electronically excited states. J. Am. Chem. Soc. 1978, 100, 4496–4503. [CrossRef]
30. Wöhrle, D.; Tausch, M.W.; Stohrer, W.-D. Photochemie: Konzepte, Methoden, Experimente; Wiley-VCH: Weinheim, Germany, 1998;
pp. 1262–1269.
31. Gnaim, S.; Green, O.; Shabat, D. The emergence of aqueous chemiluminescence: New promising class of phenoxy 1,2-dioxetane
luminophores. Chem. Commun. 2018, 54, 2073–2085. [CrossRef]
32. Yue, L.; Liu, Y.-J. Mechanism of AMPPD Chemiluminescence in a Different Voice. J. Chem. Theory Comput. 2013, 9, 2300–2312.
[CrossRef]
33. Catalani, L.H.; Wilson, T. Electron transfer and chemiluminescence. Two inefficient systems: 1,4-dimethoxy-9,10-
diphenylanthracene peroxide and diphenoyl peroxide. J. Am. Chem. Soc. 1989, 111, 2633–2639. [CrossRef]
34. Takano, Y.; Tsunesada, T.; Isobe, H.; Yoshioka, Y.; Yamaguchi, K.; Saito, I. Theoretical Studies of Decomposition Reactions of
Dioxetane, Dioxetanone, and Related Species. CT Induced Luminescence Mechanism Revisited. Bull. Chem. Soc. Jpn. 1999, 72,
213–225. [CrossRef]
35. Isobe, H.; Takano, Y.; Okumura, M.; Kuramitsu, S.; Yamaguchi, K. Mechanistic Insights in Charge-Transfer-Induced Luminescence
of 1,2-Dioxetanones with a Substituent of Low Oxidation Potential. J. Am. Chem. Soc. 2005, 127, 8667–8679. [CrossRef]
36. Kleczka, M.; But, D.; Dylong, D.; Fendinger, C.; Marmann, V.; Wartke, C.; Griesbeck, A.G. Two Useful Directing Modes in
Singlet Oxygen Reactivity: Electrostatic Effects in the Ene Reaction with Allylic Alcoholates and a Chemoselectivity Change with
α-Alkoxy Michael Esters. ChemPhotoChem 2018, 2, 964–975. [CrossRef]
37. Krick, M.; Holstein, J.J.; Wuttke, A.; Mata, R.A.; Clever, G.H. Temperature-Dependent Dynamics of Push–Pull Rotor Systems
Based on Acridinylidene Cyanoacetic Esters. Eur. J. Org. Chem. 2017, 2017, 5141–5146. [CrossRef]
38. Lehnert, W. Verbesserte Variante der Knoevenagel-Kondensation mit TiCl4/THF/Pyridin (I). Alkyliden-und Arylidenmalonester
◦
bei 0–25 C. Tetrahedron Lett. 1970, 54, 4723–4724. [CrossRef]
39. Lehnert, W. Knoevenagelkondensationen mit Titantetrachlorid/Base—II: Alkyliden- und Arylidenacet- bzw. -Nitroessigester bei
◦
0–22 . Tetrahedron 1972, 28, 663–666. [CrossRef]
40. Lehnert, W. Knoevenagelkondensationen mit TiCl4/Base—III: Umsetzungen von Ketonen und α-Halogenketonen mit Malonester.
Tetrahedron 1973, 29, 635–638. [CrossRef]
41. Lehnert, W. Knoevenagelkondensationen mit TiCl4/Base-IV: Umsetzungen von Aldehyden und Ketonen mit Phosphonoessigester
und Methylendiphosphonsäureestern. Tetrahedron 1974, 30, 301–305. [CrossRef]
42. Würth, C.; Grabolle, M.; Pauli, J.; Spieles, M.; Resch-Genger, U. Relative and absolute determination of fluorescence quantum
yields of transparent samples. Nat. Protoc. 2013, 8, 1535–1550. [CrossRef]
43. Yuasa, J.; Yamada, S.; Fukuzumi, S. Detection of a Radical Cation of an NADH Analogue in Two-Electron Reduction of a
Protonated p-Quinone Derivative by an NADH Analogue. Angew. Chem. Int. Ed. 2008, 47, 1068–1071. [CrossRef]

Molecules 2021, 26, 3305
13 of 13
44. Lee, J.Y.; Lee, Y.-M.; Kotani, H.; Nam, W.; Fukuzumi, S. High-valent manganese(v)–oxo porphyrin complexes in hydride transfer
reactions. Chem. Commun. 2009, 704–706. [CrossRef] [PubMed]
45. Wang, P.; Yao, Y.; Xue, M. A novel fluorescent probe for detecting paraquat and cyanide in water based on pillar[5]arene/10-
methylacridinium iodide molecular recognition. Chem. Commun. 2014, 50, 5064–5067. [CrossRef]
46. Albrecht, S.; Brandl, H.; Ciscato, L.F.; Weiss, D.; Augustin, D.; Zimmermann, T. The cold light of the olefins. CHIUZ 2011, 45,
24–30.
47. Schiessl, K.; Roller, A.; Hammerschmidt, F. Determination of absolute configuration of the phosphonic acid moiety of fosfazino-
mycins. Org. Biomol. Chem. 2013, 11, 7420–7426. [CrossRef] [PubMed]
48. Brachais, C.H.; Huguet, J.; Bunel, C. Synthesis, characterization and stabilization of poly(methyl glyoxylate). Polymer 1997, 38,
4959–4964. [CrossRef]
49. Beutner, S.; Bloedorn, B.; Hoffmann, T.; Martin, H.D. Synthetic singlet oxygen quenchers. Methods Enzym. 2000, 319, 226–241.
50. Data from Crystal Structure Analyses Are Deposited at the Cambridge Crystallographic Data Centre (CCDC) with Deposition
Numbers CCDC 2080452 (Compound 14) and CCDC 2080453 (Compound 15). Available online: https://www.ccdc.cam.ac.uk/
(accessed on 31 May 2021).