Investigations on the synthesis and chemiluminescence of novel 2-coumaranones

Article abstract of DOI:10.3998/ark.5550190.0014.314

Optimized syntheses of 2-coumaranone derivatives and, based thereon, several new representatives of this class of substances are described. They show a clearly visible chemiluminescence under the exposure of a strong base and in the presence of oxygen. The wavelength and intensity of the light emitted depends on both the substituents on the benzo annealed, as well as on the type of base used. A mechanism is presented in which a delocalized enolate is postulated as a key intermediate. ARKAT-USA, Inc.

Full text of DOI:10.3998/ark.5550190.0014.314

General Papers
ARKIVOC 2013 (iii) 174-188
Investigations on the synthesis and chemiluminescence
of novel 2-coumaranones
Stefan Schramm,a Dieter Weiß,*a Isabelle Navizet,b,c Daniel Roca-Sanjuán,d Herbert
Brandl,a Rainer Beckert,a and Helmar Görlsa
a Friedrich-Schiller-Universität Jena, Institut für Organische Chemie und Makromolekulare
Chemie, Humboldtstraße 10, 07743 Jena, Germany
b Molecular Science Institute, School of Chemistry, Univesity of the Witwatersrand, PO Wits,
Johannesburg, 2050 South Africa
c Université Paris-Est, Laboratoire Modélisation et Simulation Multi Echelle, MSME UMR 8208
CNRS, 5 bd Descartes, 77454 Marne-la-Vallée, France
d Department of Chemistry - Ångström, Theoretical Chemistry Programme, Uppsala University,
75002 Uppsala, Sweden
E-mail: c5diwe@rz.uni-jena.de
Dedicated to Prof. Dr. Steffen Albrecht 20.10.1957 - 19.07.2012
Abstract
Optimized syntheses of 2-coumaranone derivatives and, based thereon, several new
representatives of this class of substances are described. They show a clearly visible
chemiluminescence under the exposure of a strong base and in the presence of oxygen. The
wavelength and intensity of the light emitted depends on both the substituents on the benzo
annealed, as well as on the type of base used. A mechanism is presented in which a delocalized
enolate is postulated as a key intermediate.
Keywords: Chemiluminescence, dioxetanone, 2-coumaranone, Tscherniac-Einhorn reaction
Introduction
Chemiluminescence is the emission of ultraviolet, visible or infrared light by the release of
energy from a chemical reaction. The applications of chemiluminescence span children’s toys,
commercially available glow sticks, gas analysis (e.g. ozone-induced chemiluminescence) and
the detection and assay of biomolecules (“ELISA,” “Western blots”) and enzymes (“AMPPD”).
Even ultra-weak chemiluminescence is a frequently used method for trace analyses due to high-
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performance detectors. Generally, most chemiluminescence systems known today display only
very weak or weak light emission.1-4 On the other hand, there is still a need for strongly emitting
systems such as firefly luciferin and coelenterazine; both are important reagents for bioorganic
analytics; however, their synthesis is very complex and expensive. Based on these facts,
Lofthouse et al.5 developed a promising system in 1979 by using derivatives of 2-coumaranones
(Scheme 1).
O
HN
O
R
O
O
1
(a) R = Cl
(b) R = Br
(d) R = Me
(e) R = OMe
(c) R = [CH2]8Me
Scheme 1. 2-Coumaranone's derivatives of Lofthouse et al.
Upon treatment in polar and aprotic solvents, the solutions of 1a showed a clearly visible
blue chemiluminescence (Figure 1, 1a) on contact with air. Luminol, as a known
chemiluminophore, is under the same conditions strongly exceeded by this system in both
intensity and duration. The authors focused their activities on the exploration of the synthesis and
the elucidation of the mechanism of the chemiluminescent reaction.
Figure 1. Chemiluminescence of (1a).
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The 2-coumaranone's derivatives, despite their superior features, were lost in obscurity for a
long time, and they only aroused renewed interest almost two decades after their discovery.6-9 In
addition to principal improvements of the synthesis, B. Matuszczak reported several new benzo-
fused derivatives (Scheme 2).
Scheme 2. 2-Coumaranone derivatives synthesized by Matuszczak.
Particularly noteworthy is the attempt to integrate this type of compounds into an analytical
application in the form of a peroxidase assay. Based on these earlier works, we are now
presenting several new derivatives of the family of 2-coumaranones which show some unusual
spectral features.
Results and Discussion
Both Matuszczak and Lofthouse et al. realized the synthesis of the target substances in the same
way. We have optimized the process in detail but we used in principle the same method (Scheme
3).
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Scheme 3. Synthesis of the new compounds.
Starting with glyoxylic acid (7) and an amide or a urethane (6), we first isolated the
corresponding secondary amide (8). This was then transformed in the presence of a phenol by a
Tscherniac-Einhorn reaction,10,11 and catalyzed by concentrated sulfuric acid to give the
corresponding α-amidoalkylation products (9). In addition to this "two-step" synthesis also a
"one-pot" version is possible. Details are given in the experimental section. In the last step, water
was eliminated by treatment with acetic anhydride forming the desired lactone (5). All
compounds with phenylic structures in their side chain can be regarded as being derivatives of α-
hydroxyhippuric acid. This commercially available building-block can alternatively be prepared
according to the literature.12-15 The synthesis of (5g) was accomplished starting from myristic
acid amide, which is synthetically easily accessible from myristic acid. The spectral properties of
all compounds are within the expected range and are given in detail in the experimental section.
Single crystal X-ray analysis obtained from suitable single crystals of derivative (5a) allowed an
unambiguous structural assignment of this compound, as shown in Figure 4. The bond lengths
and angles are in the expected range.
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If the compounds (5) are treated with a strong base, such as 1,8-diazabicyclo [5.4.0] undec-7-
ene (DBU), in polar aprotic solvents, such as THF, DMF, acetone, or dibutyl phthalate, a strong
chemiluminescence can immediately be observed. The color of the emitted light varies
depending on the type of the substituent R1 and R2 at the fused benzo-ring, ranging from blue
(5g) to green (5a) to orange-red (5e) (Figure 2).
Figure 2. From left to right. chemiluminescence of (5g), (5a) and (5e).
The intense light emission can be observed over several minutes and can be reactivated by
supplying new oxygen from air. It can be generally stated that the more electron-poor the
aromatic center is, the more intensive is the emission of light. This is particularly achieved with
the position of the fluorine substituent on the aromatic ring, so that the chemiluminescence of the
compound (5h) is clearly visible even in daylight. On the other hand, the introduction of a nitro
group, as in derivative (5f), resulted in the complete quenching of the chemiluminescence. The
fact that the more electron-poor the aromatic center is, the more intensive is the emission of light,
could be explained by the higher stability of the corresponding anion formed, making the
hydrogen atom more acid. The fact that the nitro derivative does not lead to CL emission might
be explained by the much higher stability of the anion, making it less reactive to oxygen. The
chemiluminescence spectra of the new compounds (5a-c) and the fluorescence of the resulting
spent solutions are depicted in Figure 3, whereas the data of all other compounds are summarized
in Table 1.
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Figure 3. Chemiluminescence spectra of (5a-c) and Fluorescence spectra of the resulting spent
solution of (5a-c).
Table 1. Chemiluminescence of synthesized compounds and Fluorescence of the resulting spent
solution spectra maxima
Compound
Chemiluminescence, Fluorescence,
(nm)
514
512
490
498
562
452
448
-
(nm)
486
494
480
500
559
458
450
482
(5a)
(5b)
(5c)
(5d)
(5e)
(5g)
(5h)
(10)
Surprisingly, the wavelength of the chemiluminescence of all derivatives measured differs
substantially from the wavelength of the fluorescence of the resulting spent solution. This shift
probably resulted from a change in molecular geometry after chemiluminescent light have been
emitted. Such differences between the spectra have been observed only rarely, however, they
have been explained by quantum chemical methods.16 Moreover, theoretical investigations are
currently being performed and will be published separately.
Lofthouse et al. were able to postulate a suitable mechanism for the base-induced
chemiluminescence of selected members of type (1) due to the isolation of stable oxidation
products. Analogously, we succeeded in the isolation of the final oxidation product of the
chemiluminescence reaction of (5a). For this purpose, equimolar ratios of (5a) and DBU were
stirred in acetone under an oxygen atmosphere for several days. When the reaction was
completed (TLC), the isolation was carried out by several consecutive chromatographical steps.
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Spectroscopic methods and the comparison with an authentic sample revealed the structure of N-
benzoyl-5-bromo-2-hydroxybenzamide (Scheme 4).
Scheme 4. Product of the chemiluminescence of (5a).
Finally, the fluorescence spectrum of derivative 10 was recorded. Its comparison with that of
the resulting spent solution of 5a revealed only a small difference of 4 nm of the maximum.
Thus, it can be assumed that compound (10) or its deprotonated form constitutes the main
product of the chemiluminescence reaction of lactone (5a). Therefore, we suggest the following
mechanism (Scheme 5) in analogy to Lofthouse et al.
The first step is undoubtedly the deprotonation of the lactone by the base DBU on the ring α-
carbon. The direct addition of (triplet) oxygen to the deprotonated substrate, yielding the
peroxyanion (13), is spin-forbidden and cannot occur unless there is a spin inversion involved
(inter-system crossing), which is facilitated via a spin-orbit coupling. A different pathway would
leads the electron-rich enolate (11) thus formed, undergoes a single electron transfer (SET) in the
presence of oxygen from air which forms a radical (12). Then, a further molecule of oxygen is
attacked leading, via a peroxide radical, to the hydroperoxide anion (13). In the last step, this
anion attacks the lactone carbonyl group intramolecularly under the formation of an 1,2-
dioxetanone ring system (14). It is well-known that such strained four-rings are able to split up
carbon dioxide under the emission of light.18
Hitherto, only DBU was used as a base for initiating the chemiluminescence reaction
observed in our experiments. This enabled a mostly suitable activation of the reaction. Other
types of bases were examined in order to optimize the light emission. Therefore, the
chemiluminescence of compound (5a) in THF solutions (c = 10-2 mol/l) was measured. The
details are given in the experimental section. All pKA-values presented are given in relation to
acetonitrile as solvent19 and the results are depicted in Table 2.
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Scheme 5. Postulated mechanism of the chemiluminescence reaction of (5a).
Table 2. Chemiluminescence intensity with different bases
Base
Phosphazenbase, P2-Et
DBU
pKa (MeCN) Chemiluminescence
+32,94
+24,34
+23,89
+23,30
+19,56
+18,82
+18,29
+12,53
90,2 %
58,0 %
40,4 %
34,9 %
DBN
Tetramethylguanidine
Pyrrolidine
Triethylamine
DABCO
-
-
-
-
Pyridine
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As expected, the intensity of the emission was strongly dependent on the strength of the base
used. The maximum brightness was achieved by using the phosphazene base P2-Et with a pKA-
value of +32.94. No more luminescence could be observed visually when pyrrolidine with a base
strength of +19.56 was employed. Further qualitative tests showed that, in contrast to alkoxides
(NaOEt, KtOBu), only neutral bases are capable of initiating the chemiluminescence reaction of
coumaranone derivatives (5).
Conclusions
In conclusion we reinvestigated an old, but barely noticed system of chemiluminescent
substances and we succeeded in synthesizing further derivatives of similar structure. For this
purpose, the synthesis using easily available building blocks was optimized. Furthermore, the
chemiluminescence as well as the fluorescence spectra of the new derivatives were recorded.
According to a recent work of some of the authors,16 the wavelength shift between the
fluorescence and chemiluminescence spectra might be attributed to a change in the geometry of
the emissive molecule during the reaction. Exact calculations are still pending and will be
presented in further publications. Also, the possible mechanism of the reaction reported here will
be examined in more detail. The influence of base strength on the emission intensity was
qualitatively evaluated.
Due to their simple synthetic entry and their strong chemiluminescence, derivatives of type
(5) not only form the base for show experiments but also may serve for the development of new
substrates for biochemical/medicinal applications.
Experimental Section
General. All reagents, unless otherwise noted, were received by commercial providers (Sigma-
Aldrich®, TCI®, Acros Organics®) and were used in the offered quality. All for the reactions
require solvents were used in synthesis quality. Solvents which are marked with "dry", have been
dried prior to use by conventional methods and distilled under nitrogen.
The progress of the synthesis was monitored by thin layer chromatography (Merck®, silica gel 60
F254). The detection of the substances on the plates was carried out with UV light of
wavelengths 254nm and 366nm.
The listing of the NMR signals can be explained as follows: chemical shift in ppm (multiplicity,
integral, assignment). The multiplicity is indicated by the acronyms s (singlet), d (doublet), dd
(double dupplett), t (triplet), q (quartet) and m (multiplet).
The UV-VIS spectra were recorded on a Thermo UNICAM UV 500 and SHIMADZU UV-1601,
chemiluminescence and fluorescence spectra on a JASCO FP-6500. The tempering of samples
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was carried out by a LAUDA RK8 CS. The precise measurement parameters are given in the
analytical procedures.
All NMR spectra were recorded on a Bruker AC 250 (1H: 250 MHz, 13C: 63 MHz) and AC 400
(1H: 400 MHz, 13C: 100 MHz). As an internal standard a chemical shift of the residual protons of
the deuterated solvent was used in each case. The mass spectra were recorded on the devices
FISONS Trio-200, FINNIGAN MAT SSQ 710 and SHIMADZU Biotech Axima LNR.
In general, the synthesis of the targets molecules was performed in two different ways:
Route 1. "3-step synthesis"
(a) amid coupling
0.1 mol amide and 0.11 mol of glyoxylic acid monohydrate are dissolved in 75 ml of acetone in a
250 ml two-necked flask. After attaching a reflux condenser with drying tube and a thermometer
it is stirred for 5 hours under reflux. After 2 hours the reaction product begins to precipitate.
After the completion of the reaction, the reaction mixture is cooled to room temperature. This
leads to the further crystallization of the secondary amide. Finally, the product is filtered off
through a G2 frit and dried under vacuum.
b) Tscherniac-Einhorn reaction
0.03 moles of the secondary amide together with 0.035 mol of the corresponding phenol
component are dissolved in a 100 ml round bottom flask with 50 ml of an acetic acid-
concentrated sulfuric acid (9:1) mixture, and stirred for at least 24 hours at room temperature.
The exact reaction times can be found in the corresponding product description. The reaction
mixture is transferred into 250 ml of cold water. In this process the product of the Tscherniac-
Einhorn reaction precipitates. This is filtered off and used immediately for the lactonization. If
there is no precipitation the aqueous phase is extracted with chloroform. The resulting organic
phase is dried over sodium sulfate and concentrated in vacuum. The product thus obtained is
used directly for further reaction.
c) lactonization
The resulting product of the Tscherniac-Einhorn reaction is given into a two necked flask
equipped with a reflux condenser, a drying tube and a thermometer. After that it is suspended in
10 ml of acetic anhydride and stirred at reflux for 30 minutes. After completion of the reaction,
the reaction mixture is cooled to room temperature and allowed to stand overnight in the
refrigerator. If the product crystallized in the following it is filtered. If no crystals are forming,
the reaction mixture is treated with -20°C cold diethyl ether. After this the precipitate is filtered
off and dried under vacuum.
Route 2. „One pot synthesis”
a) amid coupling und Tscherniac-Einhorn reaction
0.03 moles of the amide together with 0.03 mol glyoxylic acid monohydrate are dissolved in a
100 ml round bottom flask with 50 ml of an acetic acid-concentrated sulfuric acid (9:1) mixture.
After 30 minutes of stirring at room temperature 0.035 mol of the corresponding phenol
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component are added. Now it is stirred for at least 24 hours at room temperature. The exact
reaction times can be found in the corresponding product description. The reaction mixture is
transferred into 250 ml of cold water. This is filtered and used immediately for the lactonization.
If there is no precipitation the aqueous phase is extracted with chloroform. The resulting organic
phase is dried over sodium sulfate and concentrated in vacuum. The product thus obtained is
used directly for further reaction.
b) lactonization
The lactonization at Route 2 is the same as at Route 1
N-(5-Bromo-2-oxo-2,3-dihydrobenzofuran-3-yl)benzamide (5a). According to route 1b and c
starting form alpha hydroxy hippuricacid and para-bromophenol, 24 h stirring, white powder, mp
1
235 °C (dec.), Yield: 20%; H-NMR: (250 MHz, THF-d8): δ 8.8 (d, 1H, NH), 7.8 (m, 2H,
Phenyl), 7.4 (m, 5H, Phenyl), 7.1 (d, 1H, Phenyl), 5.6 (d, 1H, CH); 13C-NMR: (62.5 MHz, THF-
d8): δ 169.9, 164.3, 151.6, 131.3, 130.3, 129.7, 127.1, 126.3, 125.4 ,125.1, 114.1, 110.2, 49.1;
MS:(EI): m/z (%) 331.4 [M+], 313.4 (50), 105.1 (100), 77.1 (95); IR (KBr): [cm-1] 3336, 3084,
2937, 1827, 1640, 1520, 1469, 1323, 1126, 1075; Elemental analysis: C15H10NO3Br calculated:
C, 54.24; H, 3.03; N, 4.22; Br, 24.06; found: C, 54.23; H, 2.81; N, 3.96 Br, 23.90
X-RAY:
Figure 4. Molecular structure and numbering scheme of (5a). The ellipsoids represent a
probability of 40%, H atoms are drawn with arbitrary radii.
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N-(5-Chloro-2-oxo-2,3-dihydrobenzofuran-3-yl)benzamide (5b). According to route 1b and c
starting form alpha hydroxy hippuricacid and para-chlorophenol, 24h stirring, white powder, mp
1
240 °C (dec.), Yield: 28%; H-NMR: (250 MHz, THF-d8): δ 8.7 (d, 1H, NH), 7.9 (m, 2H,
Phenyl), 7.4 (m, 5H, Phenyl), 7.1 (d, 1H, Phenyl), 5.6 (d, 1H, CH); 13C-NMR: (62.5 MHz, THF-
d8): δ 170.1, 164.3, 151.1, 131.3, 129.7, 127.3, 126.9, 126.6, 126.3, 125.4,122.3, 109.7, 49.2;
MS:(EI): m/z (%) 287.4 [M+] , 269.4 (65), 105.2 (100), 77.1 (95); IR (KBr): [cm-1] 3332, 3081,
2936, 1826, 1639, 1519, 1466, 1323, 1076; Elemental analysis: C15H10NO3Cl calculated: C,
62.62; H, 3.50; N, 4.87; Cl, 12.32; found: C, 62.36; H, 3.43; N, 4.68; Cl, 12.12.
N-(5-Fluoro-2-oxo-2,3-dihydrobenzofuran-3-yl)benzamide (5c). According to route 1b and c
starting form alpha hydroxy hippuricacid and para-fluorophenol, 24h stirring, white powder, mp
249 °C (dec.), Yield: 8%; 1H-NMR: (250 MHz, THF-d8): δ 8.8 (s, 1H, NH), 7.8 (m, 2H, Phenyl),
7.5 (m, 3H, Phenyl), 7.1 (m, 3H, Phenyl); 13C-NMR: (62.5 MHz, THF-d8): δ 171.9, 166.1, 157.5,
149.9, 132.3, 131.7, 128.4, 127.4, 124.1, 118.1, 117.7, 112.0, 111.8, 110.3, 62.4; MS:(EI): m/z
(%) 271.5 [M+], 253.4 (80), 105.1 (100), 77.1 (95); IR (KBr): [cm-1] 3411, 3368, 3079, 1795,
1666, 1509, 1474, 1293, 1194, 1136, 1089, 794, 712; Elemental analysis: C15H10NO3F
calculated: C, 66,42; H, 3,72; N, 5,16; found : C, 66,68; H, 3,05; N, 4,98.
N-(5-Bromo-2-oxo-2,3-dihydrobenzofuran-3-yl)-4-methylbenzamide (5d). According to
route 1b and c starting form p-methyl alpha hydroxy hippuricacid and para-bromophenol, 24h
stirring, white powder, mp 252 °C (dec.), Yield: 9%; 1H-NMR: (250 MHz, DMSO-d6): δ 9.7 (d,
1H, NH), 7.5 (m, 7H, Phenyl), 5.5 (d, 1H, CH), 2.3 (s, 3H, CH3); 13C-NMR: (62.5 MHz, DMSO-
d6): δ 173.3, 166.4, 153.2, 142.7, 132.7, 132.4, 129.8, 129.5, 127.9, 126.9, 116.2, 112.9, 51.6,
21.5; MS:(EI): m/z (%) 345 [M+], 329 (20), 119 (100), 91 (80), 65 (60); Elemental analysis:
C16H12NO3Br calculated: C, 55.51; H, 3.49; N, 4.05; Br, 23.08; found: C, 55.38; H, 3.62; N, 4.20
Br, 23.36;
N-(5-Bromo-2-oxo-2,3-dihydrobenzofuran-3-yl)-4-brombenzamide (5e). According to route
1b and c starting form p-bromo alpha hydroxy hippuricacid and para-bromophenol, 24 h stirring,
1
pale yellow powder, mp 256 °C (dec.), Yield: 7%; H-NMR: (250 MHz, DMSO-d6): δ 9.9 (d,
1H, NH), 7.5 (m, 7H, Phenyl), 5.6 (d, 1H, CH); 13C-NMR: (62.5 MHz, DMSO-d6): δ 173.1,
165.7, 153.2, 132.5, 132.4, 131.8, 130.0, 129.2, 127.1, 126.5, 116.2, 113.0, 51.7; MS:(EI): m/z
(%) 411 [M+], 393 (20), 183 (100), 155 (36), 76 (20); Elemental analysis: C15H9NO3Br2
calculated: C, 43.83; H, 2.21; N, 3.41; Br, 38.88; found: C, 43.98; H, 2.03; N, 3.25; Br, 38.51.
N-(5-Bromo-2-oxo-2,3-dihydrobenzofuran-3-yl)-4-nitrobenzamide (5f). According to route 2
starting form para-nitrobenzamide, glyoxylic acid monohydrate and para-bromophenol, 24 h
stirring, white powder, mp 186 °C (dec.), Yield: 6%; 1H-NMR: (250 MHz, DMSO-d6): δ 10.1 (d,
1H, NH), 7.0 (m, 7H, Phenyl), 5.6 (d, 1H, CH); 13C-NMR: (62.5 MHz, DMSO-d6): δ 172.9,
166.7, 153.2, 149.5, 140.4, 138.2, 132.6, 129.5, 127.2, 123.8, 116.5, 113.0, 51.7; MS:(EI): m/z
(%) 376 [M+], 358 (30), 166 (92), 150 (100), 104 (80), 76 (75); Elemental analysis:
C15H9N2O5Br calculated: C, 47.77; H, 2.41; N, 7.43; Br, 21.19; found: C, 47.97; H, 2.38; N,
7.66; Br, 20.87.
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N-(5-Bromo-2-oxo-2,3-dihydrobenzofuran-3-yl)tetradecanamide (5g). According to route 2
starting form myristic acid amide, glyoxylic acid monohydrate and para-bromophenol, 48 h
1
stirring, white powder, mp 124 °C (dec.), Yield: 7%; H-NMR: (250 MHz, DMSO-d6): δ 9.0(d,
1H, NH), 7.3 (m, 3H ,Phenyl), 5.3 (d, 1H, CH), 2.1 (t, 2H, CH2), 1.4 (m, 2H, CH2), 1.2 (m, 20H,
13
CH2), 0.8 (t, 3H, CH3); C-NMR: (62.5 MHz, DMSO-d6): δ 173.2, 153.1, 132.3, 129.6, 126.8,
116.0, 112.9, 51.1, 34.7, 31.7, 29.47, 29.45, 29.40, 29.1, 28.7, 25.4, 22.5, 14.4; MS:(EI): m/z (%)
437 [M+], 211 (28), 199 (100), 57 (48), 43 (72); Elemental analysis: C22H32NO3Br calculated: C,
60.27; H, 7.36; N, 3.19; Br, 18.23; found: C, 60.44; H, 7.46; N, 3.02; Br, 18.01.
Butyl 5-fluoro-2-oxo-2,3-dihydrobenzofuran-3-ylcarbamat (5h). According to route 2 starting
form n-butylcarbamate, glyoxylic acid monohydrate and para-fluorophenol, 48 h stirring, white
1
powder, mp 136 °C (dec.), Yield: 43%, no lactonization needed; H-NMR: (250 MHz, DMSO-
d6): δ 8.4 (d, 1H , NH), 7.3 (m, 3H ,Phenyl), 5.2 (d, 1H, CH), 3.9 (t, 2H, CH2), 1.5 (m, 2H, CH2),
13
1.2 (m, 2H, CH2), 0.9 (t, 3H, CH3); C-NMR: (62.5 MHz, DMSO-d6): δ 173.6, 153.9, 130.3,
129.1, 128.1, 122.4, 116.9, 112.4, 62.8, 53.1, 31.1, 18.7, 14.5; MS:(ESI): m/z (%) 267 [M+];
Elemental analysis: C13H14NO4F calculated: C, 58.42; H, 5.28; N, 5.24; found: C, 58.16; H, 5.10;
N, 5.41.
Analytical methods
Qualitative (visual) observation. For pure visual observation of the chemiluminescence about
10 mg of the analyte were dissolved in about 2 ml of dibutyl phthalate, or DMF and 20 µl of
DBU were added. The chemiluminescence is instantly visible for several minutes in a dimmed
room and can be renewed by shaking the reaction vessel.
Chemiluminescence and fluorescence spectra. All measurements were performed in a 10-2
molar THF solution of the analyte. Unless otherwise indicated, they were carried out at 20 °C. In
detail, there are 20 µl DBU pipetted into the 2 ml tempered analysis solution submitted in the
cuvette. After this the chemiluminescence spectra were recorded. After the decay of the
chemiluminescence (typically after 30 min), the fluorescence was measured at an excitation
wavelength of 360 nm. All Chemiluminescence intensities using different bases were expressed
relative with respect to the absolute white out of a grayscale picture of a solution of the analyte
after the addition of different bases under room conditions.
Crystal Structure Determination. The intensity data for the compounds were collected on a
Nonius KappaCCD diffractometer using graphite-monochromated Mo-Kα radiation. Data were
corrected for Lorentz and polarization effects but not for absorption effects.20, 21
The structures were solved by direct methods (SHELXS 22) and refined by full-matrix least
squares techniques against Fo2 (SHELXL-97 22). The hydrogen atom of the amine-group N1
was located by difference Fourier synthesis and refined isotropically. All other hydrogen atoms
were included at calculated positions with fixed thermal parameters. All non-hydrogen atoms
were refined anisotropically.22 XP (SIEMENS Analytical X-ray Instruments, Inc.) was used for
structure representations.
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Crystal Data for (5a). C15H10BrNO3, Mr = 332.15 gmol-1, colourless prism, size 0.06 x 0.02 x
0.02 mm3, monoclinic, space group P 21/c, a = 9.0165(4), b = 5.0121(2), c = 28.1800(9) Å, β =
95.402(2)°, V = 1267.84(9) Å3 , T= -140 °C, Z = 4, ρcalcd. = 1.740 gcm-3, µ (Mo-Kα) = 32.48 cm-
1, F(000) = 664, 6851 reflections in h(-11/9), k(-6/6), l(-36/36), measured in the range 2.81° ≤ Θ
≤ 27.49°, completeness Θmax = 98.5%, 2881 independent reflections, Rint = 0.0695, 2005
reflections with Fo > 4σ(Fo), 185 parameters, 0 restraints, R1obs = 0.0765, wR2obs = 0.1190, R1all
= 0.1193, wR2all = 0.1331, GOOF = 1.233, largest difference peak and hole: 0.520 / -0.494 e Å-3.
Supporting Information available. Crystallographic data (excluding structure factors) has been
deposited with the Cambridge Crystallographic Data Centre as supplementary publication
CCDC-880411 for (5a). Copies of the data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [E- mail: deposit@ccdc.cam.ac.uk].
Acknowledgments
I.N. thanks the financial assistance of the South African National Research Foundation (NRF)
and the university of the Witwatersrand (SPARC). D.R.-S. acknowledges the Swedish Research
Council and the projects CTQ2010-14892 and CSD2007-0010 Consolider Ingenio in Molecular
Nanoscience of the Spanish MICINN/FEDER and the Generalitat Valenciana.
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