Four- and Five-Component Syntheses and Photophysical Properties of Emission Solvatochromic 3-Aminovinylquinoxalines

Article abstract of DOI:10.1021/acs.joc.6b02581

3-Aminovinylquinoxalines are readily accessible from (hetero)aryl glyoxylic acids or heterocyclic π-nucleophiles by consecutive four- and five-component syntheses in the sense of an activation-alkynylation-cyclocondensation-addition sequence or glyoxylati

Full text of DOI:10.1021/acs.joc.6b02581

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Article
Four- and Five-component Syntheses and Photophysical
Properties of Emission Solvatochromic 3-Aminovinylquinoxalines.
Charlotte F. Gers-Panther, Henry Fischer, Jan Nordmann, Theresa Seiler, Thomas
Behnke, Christian Würth, Walter Frank, Ute Resch-Genger, and Thomas J. J. Mueller
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02581 • Publication Date (Web): 15 Dec 2016
Downloaded from http://pubs.acs.org on December 16, 2016
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The Journal of Organic Chemistry
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Four- and Five-component Syntheses and Photophysical Properties
of Emission Solvatochromic 3-Aminovinylquinoxalines.
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Charlotte F. Gers-Panther,† Henry Fischer,‡ Jan Nordmann,† Theresa Seiler,† Thomas Behnke,‡
Christian Würth,‡ Walter Frank,§ Ute Resch-Genger,*,‡ and Thomas J. J. Müller*,†
†Institut für Organische Chemie und Makromolekulare Chemie, Heinrich-Heine-Universität Düsseldorf,
Universitätsstrasse 1, D-40225 Düsseldorf, Germany
‡Bundesanstalt für Materialforschung und -prüfung (BAM), Richard-Willstätter-Strasse 11, D-12489 Berlin, Germany
§Institut für Anorganische Chemie und Strukturchemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstrasse
1, D-40225 Düsseldorf, Germany
KEYWORDS. Copper – Cross-coupling – DFT-calculations – Fluorescence – Heterocycles – Multi-component reac-
tions –Solvatochromism.
ABSTRACT: 3-Aminovinylquinoxalines are readily accessible from (hetero)aryl glyoxylic acids or heterocyclic π-
nucleophiles by consecutive four- and five-component syntheses in the sense of an activation-alkynylation-
cyclocondensation-addition sequence or glyoxylation-alkynylation-cyclocondensation-addition sequence in good yields.
The title compounds are highly fluorescent with pronounced emission solvatochromicity and protochromic fluorescence
quenching. Time-resolved fluorescence spectroscopy furnishes radiative and nonradiative fluorescence decay rates in
various solvent polarities. The electronic structure is corroborated by DFT and TD-DFT calculations rationalizing the
observed spectroscopic effects.
Favorable for such applications are fluorophores, which
INTRODUCTION
display different emission colors depending on the
polarity of the surrounding media.8 Such compounds are
In the past decades, functional organic compounds
have increasingly received interest in the context of
materials and life sciences.1 Besides carbon-rich π-systems
and organic polymers, small organic molecules have
aroused attention in a variety of fields, ranging from
organic electronics2 (OFET, OLED, and DSSC)3 to imaging
and sensing applications in biochemical,4 environmental,
and clinical applications.5 In this area, fluorescence
generally highly polar and experience a significant change
of their dipole moment upon excitation from S0 to S1.9
This by eye-sight observable phenomenon is called
solvatochromism,10 and can occur in absorption and/or
emission.11 Such properties are commonly obtained by the
introduction of electron donating and withdrawing
moieties to a molecule.
detection adopts
a central position, offering many
The increasing demand for tailor-made fluorophores
requires constantly novel structural motifs and innovative
synthetic approaches. For establishing reliable structure-
property relationships of the photophysical behavior of
novel compound classes, often libraries are particularly
valuable. In this context, the concepts of combinatorial
chemistry12 and diversity-oriented synthesis13 are highly
advantageous, since highly diverse products14 can be
readily attained through variation of the different starting
materials. In particular, multicomponent reactions
(MCR)15 and one-pot strategies adopt a central role, since
they combine beneficial economic and ecological factors,
such as higher resource efficiency and lower waste
production compared to the classical multistep synthesis.
In the past decades, MCR regularly found application in
the synthesis of natural products16 and pharmaceutically
interesting compounds17 and more recently, they have
become a powerful tool for fluorophore design.18
advantages over other competing methods of detection.
This is related to the fact, that fluorescence is a
multiparameter technique requiring comparatively simple
and inexpensive instrumentation and offering a unique
sensitivity down to the single molecule or particle level.6
Fluorescence detection is closely linked to fluorescent
labels and probes responding to physico-chemical or
chemical quantities and changes of their local
environment
such
as
polarity,
viscosity
or
proticity/hydrogen bonding, with changes in the spectral
position and/or intensity of their absorption and emission
bands.7 This includes also the presence and concentration
of biologically or diagnostically relevant ionic or neutral
analytes such as protons or molecular oxygen. For
example, polarity sensing is often applied in molecular
cell biological and biochemical studies, i.e., for
monitoring folding and unfolding processes of proteins or
for estimating the polarity of protein binding sites.4
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In recent years, the quinoxaline core was regularly substituent. Inspired by the universal functionality of
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8
incorporated as an electron acceptor in push-pull systems
and intramolecular charge-transfer complexes (ICT)19
owing to their peculiar electronic nature. The presence of
two nitrogen atoms leads to a highly electron deficient π-
system.20 A large number of these compounds are
luminescent and their high polarity expresses itself by
pronounced solvatochromic shifts of the emission bands.
Only recently, we21 and Zhang's group22 described the
synthesis of emission-solvatochromic indole-substituted
triple bonds in synthetic organic chemistry, we became
intrigued to employ the alkyne functionality for
subsequent transformations, eventually in a one-pot
scenario. Ethynylquinoxalines should be susceptible to
nitrogen nucleophiles, in analogy to alkynones31 or
classical Michael systems (Scheme 2), caused by the
electron-withdrawing character of the quinoxaline core,
furnishing enamine-type structures.32 Similar strategies
were also employed in the synthesis of various
heterocyclic scaffolds through an intramolecular ring
closure.32b,33
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quinoxaline
derivatives.
Another
solvatochromic
quinoxaline-based push-pull system was reported by
Kudo et al. which was employed to classify the binding-
site polarity of bovine serum albumin23 and even shows
site-dependent fluorescence in HEp-2 cells.24 The
electron-withdrawing character of quinoxalines has also
led to their incorporation into chromophores for dye-
sensitized solar cells.25
Scheme
2.
Electrophilicity
mapping
of
ethynylquinoxalines.
In general, quinoxalines are easily accessible by
cyclocondensation of 1,2-diaminoarenes and 1,2-
dicarbonyl compounds,26 the so called Hinsberg
reaction.27 Interestingly, quinoxalines are hardly found in
natural products, nevertheless many synthetic derivatives
possess biological activities28 with some being accounted
to the best-selling drugs containing six-membered
heterocycles.29 Our group has recently reported two
complementary diversity-oriented one-pot approaches for
the synthesis of quinoxaline derivatives through
intermediary reactive ynediones (Scheme 1).21 In the first
step, both methods generate glyoxylic acid chlorides
starting either from a π-nucleophile 1 or a glyoxylic acid 2,
which are subsequently converted into ynediones 4
The addition of nitrogen-based nucleophiles to the
triple bond would ultimately result in a second strongly
electron-donating substituent on the quinoxaline core,
namely an aminovinyl group.34 Aminoquinoxaline-based
push-pull systems had previously been a subject of
photophysical studies, however, both units were either
ligated by a phenyl35 or styryl19b linker. Here, we report
four- and five-component syntheses of novel 3-
aminovinylquinoxalines, their structures and first studies
of their photophysical properties and their electronic
structures.
through
a
copper-catalyzed
Stephens-Castro
alkynylation.30 The formed ynediones are subsequently
reacted with 1,2-diaminoarenes to produce the desired
quinoxalines 6, leaving the triple bond untouched. The
ethynylquinoxalines
6
are fluorescent and display
pronounced emission solvatochromism, which was
ascribed to the push-pull character between the electron-
rich heterocyclic substituent R1 in 2-position and the
electron deficient quinoxaline ring.
RESULTS AND DISCUSSION
Synthesis. For studying the addition of secondary
amines to the triple bond, a terminally unsubstituted
ethynylquinoxaline and pyrrolidine were chosen as model
substrates to ensure a high reactivity. Starting from TMS-
ethynylquinoxaline 6a,21 the terminal alkyne was
quantitatively obtained by cleaving of the TMS group in
the presence of KF and methanol.36 Compound 7a can be
Scheme 1. Four-component (GACC sequence) and
three-component (AACC sequence) one-pot synthe-
ses of ethynylquinoxalines 6.
easily
transformed
into
the
desired
3-
aminovinylquinoxaline 9a upon addition of pyrrolidine
(8a) in a mixture of THF and MeOH as the solvent system
(Scheme 3). Much to our delight, the combination of
pyrrolidine and methanol generated sufficiently basic
conditions to cleave the TMS group in situ and, therefore,
enabled
a domino desilylation-addition-sequence to
obtain the corresponding 3-pyrrolidinovinylquinoxaline
9a exceeding the combined yields of the stepwise process.
These beneficial electronic properties should be
amplified by increasing the push-pull character through
the introduction of an additional, even stronger donor
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(Table 1, entries 1-3, 5, 6, 8, 9) as well as a phenyl ring
Scheme 3. Two-step and domino access to 3-
1
2
3
4
5
6
7
8
pyrrolidinovinylquinoxaline
ethynylquinoxaline 6a.
TMS
9a
from
TMS-
(Table 1, entries 4, 7, 10) with generally excellent yields.
Comparing the yields of these four-step sequences with
the yields of the three-step 3-ethynylquinoxaline
formation30a reveals that the terminal amine addition
proceeds almost quantitatively, except for employing
phenylglyoxylic acid as a starting material (Table 1, entry
4). 1,2-Diamino-4,5-dichlorobenzene (5b) and 2,3-
diaminonaphthalene (5c) can be also utilized in the
synthesis of 3-aminovinylquinoxalines, although the
yields are slightly lower (Table 4, entries 6-9). Piperidine
N
N
2.0 equiv KF
N
N
THF, MeOH
N
rt, t
N
(6a)
Me
7
( )
Me
100%
2.0 equiv
pyrrolidine (8a)
THF, MeOH, rt, 1 h
75%
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N
(8b) as
a
secondary amine furnishes the 3-
piperidinovinylquinoxaline 9j (Table 1, entry 10). Acyclic
secondary amines were not employed in the one-pot
sequence. They were found to react sluggishly in the
single-step reaction and the products partly hydrolyzed
upon chromatographic purification. Their isolation by
crystallization was neither successful. Taking into account
that six new bonds are formed in a consecutive four-step
fashion the average yields per bond forming step accounts
to 88-95%.
N
N
8a
2.0 equiv pyrrolidine (
)
THF, MeOH, rt, 1 h
83%
N
9a
(
Me
)
With this simple transformation of ethynylquinoxaline
6a to the corresponding 3-pyrrolidinovinylquinoxaline 9a
in hand, we reasoned that a concatenation of the
previously
ethynylquinoxalines should furnish an efficient access to
3-aminovinylquinoxalines in consecutive four
reported
one-pot
synthesis
of
The
proposed
structures
of
the
3-
9
a
aminovinylquinoxalines 9 were unambiguously supported
with 1H and 13C NMR-spectroscopy, mass spectrometry, IR
spectroscopy, and combustion analysis. It is noteworthy
that all derivatives were exclusively formed as single
diastereomers. The vicinal coupling constants for the
vinyl protons lie in the range of 12.6 to 12.8, suggesting the
formation of the thermodynamically favored (E)-
configuration for the double bond. The structures of
compounds 9 were additionally corroborated by X-ray
crystal structure determination of compound 9a (Figure
1).37
component or five component fashion. The particular
challenge in designing this sequence is the combination
of reaction steps proceeding in alternating pH regions,
i.e., 1) glyoxylation and activation (acidic); 2) alkynylation
(basic); 3) cyclocondensation (acidic); 4) desilylation and
amine addition (basic). This can result in a considerable
salt formation as byproducts, which often hamper the
smooth course of a reaction. Therefore, we set out to
optimize the envisaged process with a special focus on
consequently minimizing the amounts of additives, such
as triethylamine and acetic acid (see Supporting
Information, Tables S1 and S2). As a result of the
optimization study of the one-pot glyoxylation-
alkynylation-cyclocondensation synthesis of 6a (see
Supporting Information, Table S2) the concatenation with
the terminal pyrrolidine addition was probed and
optimized (see Supporting Information, Table S3). Most
importantly a sixfold excess of pyrrolidine (8a) in
conjunction with a chromatographic purification on basic
alumina with dichloromethane as an eluent proved to
furnish a yield of 76% of 3-pyrrolidinovinylquinoxaline 9a
for the four step one-pot synthesis.
These optimized conditions for preparation and
isolation were then applied to all four- and five-
component syntheses of 3-aminovinylquinoxalines
Figure 1. Left: Diagram of the molecular structure of 9a in
the crystal; right: Packing of molecules to columns. Dis-
placement ellipsoids are drawn at the 30% probability level.
Selected torsion angle: C1−C8−C9−C16 −35.7(2).
9
starting from either π-nucleophiles 1 or glyoxylic acids 2
(Table 1). Much to our delight, the sequence represents a
highly modular approach to a library of the desired
compounds mostly in excellent yields. The corresponding
3-aminovinylquinoxalines
arising
from
3-
(aryl)ethynylquinoxalines were found to hydrolyze upon
flash chromatography. It is noteworthy to mention that,
with exception of the secondary amine 8, all components
are employed in strictly equimolecular ratios. Applying
both reaction sequences allows the introduction of
different heterocyclic moieties to the quinoxaline core
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Table 1. One-pot four-step synthesis of 3-aminovinylquinoxalines 9.
1
2
3
4
5
6
7
n
N
(COCl)2 (1.0 equiv )
THF, 50 °C, 1 h
TMS
H
N
n
HO
O
O
8 (6.0 equivs)
N
N
R1
H
or
R2
N
N
then: CuI (5 mol%), 3a (1.0 equiv), NEt3, rt, 6 h
then: 5 (1.0 equiv), MeOH, HOAc, 50 °C, 1 h
R1
1-2 h, rt - 50 °C
R2
R1
R1
8
9
1
2
6
9
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Entry Starting material 1 or 2
1,2-Diamino arene 5
3-Ethynylquinoxaline
Secondary
amine 8
3-Aminovinylquinoxaline 9
6[a]
(yield)
1
1-methylindole (1a)
1-methylpyrrole (1b)
ortho-phenylene
diamine (5a)
pyrrolidine
(8a)
6a
(77%)
9a (73%)[b]
2
3
5a
5a
8a
8a
6b
(73%)
9b (74%)[b]
2-methoxythiophene
(1c)
6c
(59%)
9c
(60%)[b]
4
phenyl glyoxylic acid
5a
5a
8a
(2a)
6d
9d (57%)[b]
(85%)
5
2-thiophene glyoxylic
8a
8a
acid (2b)
6e
(69%)
9e (69%)[b]
6
1-methylindole (1a)
1,2-diamino 4,5-
dichloro benzene (5b)
-
9f
(68%)[c]
7
phenyl glyoxylic acid
5b
5b
-
-
8a
8a
(2a)
9g
(52%)[c]
8
2-thiophene glyoxylic
acid (2b)
9h
(65%)[b]
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9
2-thiophene glyoxylic
2,3-diamino naphtha-
-
8a
1
acid (2b)
lene (5c)
2
3
4
5
9i
(61%)[b]
6
10
phenyl glyoxylic acid
5a
-
piperidine
7
(2a)
(8b)
8
9
9j (46%)[d]
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[a]Yield of the intermediary 3-ethynylquinoxaline 6, if isolated. [b]Reaction conditions for the amine addition step: 1 h, rt.
[c]Reaction conditions for the amine addition step: 1 h, 50°C. [d]Reaction conditions for the amine addition step: 2 h, 50°C.
For comparison of the measured spectroscopic and the
calculated data, we considered the empirical solvent
polarity parameter ꢀꢁꢂ. ꢀꢁꢂ values are correlated to the
PHOTOPHYSICAL PROPERTIES – SPECTROSCOPIC
STUDIES AND CALCULATIONS
Solvatochromism. The solvatochromism of our four
electronic transition energies of the chromogenic dye
selected
3-aminovinylquinoxalines
9a-9d
was
pyridinium N-phenolate betaine,
a
well-established
polarity probe.11 The plot of the Stokes shift as function of
ꢀꢁꢂ values reveal the experimentally determined Δꢃ (see
Supporting Information, Figure S2, Table S2).
subsequently thoroughly studied by absorption as well as
steady state and time-resolved fluorescence spectroscopy
in nine solvents of different polarity to confirm the
theoretical assumptions, assessing absorption and
fluorescence maxima, fluorescence quantum yields
Φ, and
fluorescence lifetimes . Figure 2 compares the absorption
τ
and emission spectra of 9a-9d in acetonitrile. In the UV
region below 400 nm, all dyes show a unique absorption
pattern. The order of the longest wavelength absorption
maxima (λmax(abs)) of 9a-9d is as follows: 9d (438 nm), 9a
(440 nm), 9b (445 nm), and 9c (456 nm), respectively.
This trend is also reflected by the emission spectra in
acetonitrile shown in Figure 2, with the broad shape of
these bands underlining the charge transfer (CT)
character of this transition.
Figure 3. Emission bands of 9a in solvents of varying polarity
and proticity. from left to right: cyclohexane (magenta),
toluene (blue), tetrahydrofuran (cyan), acetone (green),
acetonitrile (orange), ethanol (red).
Additionally, the fluorescence quantum yields ꢄ and
the fluorescence lifetimes ꢅ of dyes 9a-9d were measured
in different solvents. The corresponding data are
summarized in Table 2. The highest ꢄ value of 61.1 %
resulted for 9b in dichloromethane; with values of 0.6 to
1.2 % and 2.2 to 4.8 % the lowest ꢄ are found for all dyes
in methanol and ethanol, respectively. As follows from
Table 2, dyes 9a, 9b and 9d are significantly more
emissive than dye 9c, which possesses the smallest
torsional angle between the 2-substituent, i.e., the
thiophene moiety, and the quinoxaline core. Additionally,
the heavy atom effect likely plays a role in the quenching
process. The lifetimes ꢅ of the dyes 9a-9d reveal a similar
dependence on solvent and dye structure as ꢄ. In
summary, for 9a-9d, ꢄ and ꢅ increase with increasing
solvent polarity up to ꢀꢁꢂ of about 0.3 and then decrease
with increasing polarity. The very small values in the most
polar, yet also protic solvents ethanol and methanol are
ascribed to additional contributions from hydrogen
bonding induced fluorescence quenching as observed for
many CT-operated fluorophores.
Figure 2. Normalized absorption (550 nm and below) and
emission spectra (450 nm and above) of 9a-9d in acetonitrile
(9a: blue; 9b: cyan; 9c: green; 9d: red).
The influence of the polarity of the surrounding
medium on the emission of the 3-aminovinylquinoxalines
is shown for 9a in Figure 3. In nonpolar, aprotic solvents
like cyclohexane, the dye´s emission band, located at ca.
475 nm, reveals a vibronic fine structure. With increasing
solvent polarity, this vibronic structure is lost and the
emission bands are shifted bathochromically by up to 3291
cm-1. This behavior is typical for CT-operated
fluorophores and implies a positive solvatochromism of
this family of dyes.
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Table 2. Fluorescence quantum yields and lifetimes of the dyes 9a-9d in solvents of different polarity and pro-
ticity.
1
2
3
N
ET
Solvent
9a
9b
9c
9d
4
5
6
7
8
9
ꢄ [%]
1.2
ꢅ [ns]
0.19
0.75
6.75
7.19
6.42
7.01
5.12
ꢄ [%]
0.6
ꢅ [ns]
0.12
ꢄ [%]
0.9
ꢅ [ns]
0.22
0.67
5.78
4.88
5.10
ꢄ [%]
0.6
ꢅ [ns]
0.15
0.762
0.654
0.460
0.444
0.355
0.309
0.207
0.099
0.006
methanol
ethanol
4.8
2.2
0.39
5.96
5.54
6.72
8.33
6.61
5.10
3.1
2.3
0.49
5.28
2.97
6.88
10.25
8.42
6.52
2.30
acetonitrile
DMSO
43.0
49.6
45.6
57.9
44.4
37.5
12.6
33.0
32.5
41.4
61.1
21.0
18.4
20.9
19.0
15.5
9.5
19.9
11.2
10
11
12
13
14
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acetone
28.4
59.8
44.5
49.0
18.6
dichloromethane
tetrahydofuran
toluene
3.28
2.79
1.25
49.5
46.9
18.4
3.62
1.27
cyclohexane
1.87
7.2
0.79
Subsequently, we calculated the radiative and
nonradiative rate constants ꢆꢇ and ꢆꢈꢇ of the dyes 9a-9d
from measured ꢄ and ꢅ in Table 2 (see also Supporting
Information);38 the resulting rate constants were then
plotted as function of ꢀꢁꢂ as summarized in Figure 4. As
shown in Figure 4 (right), ꢆꢇ decrease with increasing
solvent polarity for all four dyes up to ꢀꢁꢂ of about 0.3 and
then remains more or less constant, whereas ꢆꢈꢇ of 9a-9d
decrease up to ꢀꢁꢂ of about 0.3 and then strongly increases
(see Figure 4, left).
due to the formation of hydrogen bonds between the
hydroxyl groups of the alcohols and the dye molecules.40,41
This encouraged us to perform protonation studies,
thereby also assessing the dyes´ protonation sites more
closely, which are detailed in a separate section.
Calculated
electronic
structure
of
3-
aminovinylquinoxalines 9. A deeper rationalization
of the photophysical behavior of quinoxalines 9a-9d
was sought by elucidating the electronic structure by
calculating UV/vis absorption spectra on the DFT
level of theory, with a special focus on the origin of
the five longest wavelength absorption maxima of
each structure. The structures were chosen as a series
of compounds with three electron-donating (9a-9c
)
and one electron-neutral substituent (9d) in position
2 of the quinoxaline core. For this purpose, first the
geometries of the ground state structures were
optimized using Gaussian0942 with the B3LYP
functional43 and the Pople 6-311G(d,p) basis set.44
Since all measurements were recorded in solution,
the calculations were carried out using the
polarizable continuum model (PCM) applying
acetonitrile as a solvent.45 All minima structures were
confirmed by analytical frequency analyses.
The computed equilibrium ground state structure
of 9a matches with the structure obtained from X-ray
analyses. The experimentally determined torsional
angle between the
quinoxaline core is well reproduced by the
computations (θcalc 37° vs θXray 36°).
A closer inspection of the coefficient densities in
the Kohn–Sham frontier molecular orbitals of the
pyrrolidinylvinyl 9a-9d reveals that the HOMO
coefficient densities are predominantly localized on
the quinoxaline ring and the adjacent vinyl moiety,
while it is much lower on the substituent in 2-
position (Figure 5). The phenyl ring of compound 9d
bears essentially no coefficient density. Concerning
the LUMOs, a quite different picture emerges. In all
four derivatives, the coefficient density on the vinyl
N-methylindole substituent and
=
−
= −
Figure 4. The radiative (top) and nonradiatve (bottom) rate
constants plotted against ꢀꢁꢂ. 9a: triangle downwards; 9b:
square; 9c: circle; 9d: triangle upwards.
N-
High values of ꢆꢈꢇ in low polarity solvents suggest a
radiationless relaxation due to sigma bond rotations;39
such sigma bond rotations are possible for the
substituents of all quinoxalines studied. The fact that for
high ꢀꢁꢂ values, which correspond to the alcohols ethanol
and methanol, we see exclusively high values for ꢆꢈꢇ
whereas the size of ꢆꢇ remains almost constant for ꢀꢁꢂ
0.3 confirms our assumption of fluorescence quenching
>
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moiety is much less pronounced, while it is slightly
4.26a
chromophores display a substantial protochromism
upon addition of acids such as PTSA ( -toluene
Moreover,
some
quinoxaline-based
1
2
3
4
5
6
7
8
increased on the quinoxaline. This provides a clear
hint for the proposed charge transfer (CT) character
in the excited state. The effect on the 2-substituent
appears to be only minor; while a slightly lower
coefficient density is found on the indole and pyrrole
moiety, it is enhanced on the thiophene and phenyl
ring.
p
sulfonic acid).19b,48 The presence of strong acids
generally leads to the protonation of a nitrogen atom.
Compounds 9c-9d contain three, compounds 9a-9b
even four basic nitrogen atoms, which could
principally undergo protonation. We therefore
reasoned that studies on the protonation behavior of
the 3-aminovinylquinoxalines should give insights
into the reactivity of these quinoxalines. The
9
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48
49
50
51
52
53
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60
structural
resemblance
of
the
3-
aminovinylquinoxalines to vinamidines49 suggests the
quinoxaline-N1 position as the most probable
protonation site, leading to a stabilized vinamidinium
ion (Scheme 4).
Scheme 4. Mesomeric forms of the free base and its
conjugated acid.
N
N
H
N
N
R
N
R
N
a
c
H+
Figure 5. Selected DFT-computed (B3LYP 6-311G(d,p)) Kohn-
N
N
H
Sham
frontier
molecular
orbitals
of
3-N-
N
N
pyrrolidinylvinylquinoxalines 9a-9d.
The optimized structures
of
the
3-
R
N
b
R
N
d
aminovinylquinoxalines 9a-9d were subjected to TD-DFT
calculations to study the absorption characteristics (Table
3). The hybrid exchange-correlation functional CAM-
This assumption is additionally supported by a closer
inspection of the pyrrolidine and the double bond signals
B3LYP46 was implemented and
a
nonequilibrium
1
in the respective H and 13C NMR spectra (Table 5). The
solvation47 for the state-specific solvation of the vertical
excitation was included.
carbon nuclei of the pyrrolidine unit of compound 9a
appear as two signals at
protonated form two sets for both signals can be found.
δ 25.2 and 49.1, while for the
Expectedly, the longest wavelength absorption bands of
all four computed molecules 9a-9d result from
HOMO−LUMO transitions. The calculated oscillator
strength correlates nicely with the experimentally
While there is only a minor separation of the C1 nuclei (
24.7 and 24.8), the signals for C2 considerably differ (
47.6 und 53.9). A similar behavior can be observed in the
1H NMR spectrum, however, only for the protons at
position 2 (δ 3.18 and 3.95).
δ
δ
determined molar decadic extinction coefficients
ε
underlining the π-π* character of this transition.
Although the experimentally obtained absorption maxima
are slightly bathochromically shifted by 756 to 1394 cm-1
with respect to the theoretically determined maxima, the
trends revealed by theory and experiment are in excellent
agreement.
These results indicate protonation at the quinoxaline
nitrogen atom, which is in close proximity to the
aminovinyl moiety. According to the vinamidinium type
resonance structure d (Scheme 4), the carbon nuclei at
positions 1 and 2, respectively, are not magnetically
equivalent, which results in the observed signal splitting
in both 1H and 13C NMR spectra.
Additionally, the dipole moments ꢃ and the Onsager
radius ꢉ were calculated (Table 4). The dyes 9a and 9c
possess the highest dipole moments in the ground state
and in the excited state as well, followed by 9d and 9b.
The experimentally determined Δꢃ of dyes 9a-9d,
although smaller, confirm the trend of the calculated Δꢃ
values, revealing the largest change for 9d and the
smallest effects for 9b and 9a.
The proposed protonation site as well as the E-
configuration of compound 9a-H+ was additionally
supported by the two-dimensional NOESY spectrum,
where significant cross-peaks were found between the N-
proton and the two ethenyl protons. The combination
with the third cross-peak to the neighboring proton of the
quinoxaline benzene ring gives evidence for the suggested
structure (Scheme 5).
Protonation
aminovinylquinoxalines
studies
9a-9d.
quinoxalines are weakly basic, as follows from the pKa
with
In
3-
general,
of 0.56 of the parent compound shown in Scheme
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Table 3. TD-DFT calculations (CAM-B3LYP 6-311G(d,p)) of the absorption maxima of 3-aminovinylquinoxalines
9a-9d in acetonitrile.
1
2
3
4
5
6
7
8
9
Compound
Dominant contributions (%)
Experimental λmax(abs)
[nm] (
-1cm-1])
Calculated λmax(abs)
[nm]
416
[eV] (oscillator strength)
ε [m
9a
9b
9c
9d
440 (17300)
445 (20500)
456 (15300)
438 (16100)
2.98039 (0.4081)
2.95905 (0.3772)
2.81143 (0.3165)
2.95905 (0.3741)
HOMO→LUMO (96)
HOMO→LUMO (96)
HOMO→LUMO (96)
HOMO→LUMO (96)
419
441
419
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 4. Calculated values of the dipole moments
and the Onsager radius a of 9a-9d in acetonitrile
(using Gaussian09 B3LYP 6-311+ (d,p)).
Scheme 5. NOESY cross-peaks for compound 9a-H+.
N
N
H
H
H
N
H
N
H
N
H
N
Compound Dipole moment ꢃ [D]
N
N
N
ground excited state excited state radius
N
N
N
state
10.49
5.82
9.77
7.48
(non-relaxed) (relaxed)
ꢉ
Me
Me
Me
(5.68 / 15.03)
(10.13 / 15.04)
(cross peaks)
(8.59 / 15.03)
9a
9b
9c
9d
16.26
11.92
16.18
14.10
15.34
11.28
15.75
13.43
4.75
4.70
5.00
4.75
δ
Hints for the proposed protonation site were also
obtained from DFT-calculations based on the structure of
9a. A thermodynamic comparison of four different
protonated species 9a-H+ revealed the protonation at the
quinoxaline-N1 and N2 positions to be thermodynamically
most favorable (Figure 6).
13
Table 5. Comparison of characteristic 1H and C NMR
signals of free base 9a and the corresponding proto-
nated species 9a-H+.
1
1
2
2
N
N
5
3
4
3
4
H
N
N
N
N
N
N
(9a)
(9a-H+)
Me
Me
1H NMR
Position 9a
13C NMR
9a-H+
Position 9a
9a-
H+
H1
1.80-1.97
1.95-2.01
(m, 4 H)
3.18
C1
25.2
24.7
24.8
47.6
53.9
(m, 4 H)
3.28
H2
C2
49.1
(br, 4 H)
(t, J = 5.9
Figure 6. Thermodynamic comparison of four protonated
species based on 9a (Gaussian09 B3LYP/6-311G(d,p) PCM
model for the solvent acetonitrile).
Hz, 2 H)
3.95
(t, J = 6.0
Hz, 2 H)
This encouraged us to perform
a spectroscopic
protonation study representatively for two dyes, here a
titration experiment with 9a and 9d in a DMSO-water
mixture adding different amounts of hydrochloric acid
(Figure 7). As summarized in Figure 7, with increasing
proton concentration, a bathochromic shift in absorption
together with a change in spectral shape and an increase
in intensity occurred. These changes in absorption reflect
the protonation-induced weakening of the electron
donor. The observation of an isosbestic point for both
dyes (9a: 430 nm; 9d: 441 nm) underlines the formation of
H3
H4
H5
8.17
10.13
C3
C4
-
143.0 154.8
94.0 89.3
(d, J = 12.7 (d, J = 12.4
Hz, 1 H)
Hz, 1 H)
5.61
5.68
(d, J = 12.7 (d, J = 12.6
Hz, 1 H)
Hz, 1 H)
-
14.99-15.10
(br)
-
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a
single protonation product and quantitative 1:1
studying in more detail, together with the aggregation
behavior of these dyes in mixtures of organic solvents and
water and the occurrence of aggregation-induced
emission enhancement (AIEE).
1
2
3
4
5
6
7
8
transformation without side products. From the changes
in absorption, the pKa values were calculated to 4.26 for
9a-H+ and 3.7 for 9d-H+, respectively. This agrees with the
slightly higher electron density at the quinoxaline
nitrogen atom found for 9a compared to 9d according to
the Mulliken charges. The protonation was reversible as
revealed by addition of base. As shown in Figure 7,
protonation leads to a strong decrease in fluorescence for
both dyes, with the protonated species always being
nonemissive. This follows from excitation spectra
measured for different concentrations of hydrochloric
acid which show only the absorption band of the
nonprotonated (emissive) species and match with the
absorption spectrum of the corresponding dye without
hydrochloric acid. A protonation-induced fluorescence
quenching has been reported for many CT-operated dyes.
This observation agrees well with the hydrogen bonding
induced diminution in fluorescence observed in polar
protic solvents like ethanol and methanol described in a
previous section.
EXPERIMENTAL
General considerations. Reagents and solvents were
purchased reagent grade and used without further
purification. The reaction progress was observed
qualitatively using TLC silica gel 60 F254 aluminum sheets.
The spots were detected with UV light at 254 and 365 nm
9
10
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46
47
48
49
50
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52
53
54
55
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58
59
60
and with aqueous potassium permanganate solution.
1
Chemical shifts
δ
in the H NMR and 13C NMR spectra are
reported in ppm relative to CDCl . The assignments of
3
quaternary C, CH, CH2, and CH3 signals were made by
using DEPT spectra.
Spectroscopic measurements. IR spectra were
recorded with neat compounds under attenuated total
reflexion (ATR) and the intensities were characterized as
strong (s), middle (m) and weak (w). Absorption spectra
were measured with a calibrated spectrophotometer.
Emission and excitation spectra were obtained with a
calibrated spectrofluorometer equipped with polarizers in
the excitation and emission channel and were corrected
for the wavelength dependence of the spectral
responsivity of the detection channel (emission spectra;
fluorescence quantum yields) or for the spectral photon
flux of the excitation channel (excitation spectra).50 The
fluorescence quantum yields of the dyes were determined
from spectrally corrected integrated emission spectra (on
an energy scale) relative to Coumarin 153 (ꢄ = 54.1 % in
ethanol)51 using
a
previously described procedure
(excitation and emission polarizer set to magic angle
conditions), thereby also considering the refractive
indices of the solvents of the dyes 9a-9d and the reference
dyes.52 The fluorescence lifetimes were measured with a
spectrofluorometer using a pulsed excitation light source
(fs fianium laser-monochromator ensemble).
Figure 7. Spectroscopic study of the protonation of the dyes
9a (left) and 9d (right) in a DMSO-water mixture. The con-
centration of the dyes was 2 ꢀ
below) and emission (500 nm upwards) is shown by different
concentrations of hydrochloric acid (1: 0 m ; 2: 0.05 m ; 3:
0.1 m ; 4: 0.2 m ; 5: 1 m ; 6: 2.5 m ). Excitation was always
M. The absorption (550 nm and
M
M
M
M
M
M
Procedure for the synthesis of 2-Ethynyl-3-(1-
methyl-1H-indol-3-yl)quinoxaline (7a). The TMS-
protected ethynylquinoxaline 6a21 (2.31 g, 6.49 mmol) was
placed in a round flask and dissolved in tetrahydrofuran
(1 mL/mmol) and methanol (2 mL/mmol). Then, 2.0
equivs of potassium fluoride (766 mg, 13.0 mmol) were
added. After 60 min the reaction was terminated by
addition of water (10 mL), the phases were separated and
the aqueous phase was extracted with dichloromethane.
The combined organic layers were dried with anhydrous
sodium sulfate. Thereafter, the solvents were removed in
vacuo to obtain the analytically pure product 7a in
at the isosbestic point.
CONCLUSION
Four-
and
five-component
syntheses
of
3-
aminovinylquinoxalines have been established. The
diversity-oriented nature of this approach allowed the
straightforward construction of a substance library for
first
structure-property
relationship
studies.
3-
Aminovinylquinoxalines were found to be highly
fluorescent in organic solvents and mixtures of organic
solvents
solvatochromicity and protochromicity, underlining the
charge transfer character of their absorption and
emission, and reveal hydrogen bonding- and protonation-
and
water.
Moreover,
they
display
quantitative yield (1.86 g, 100%).
1
Yellow solid, 128 °C. H NMR (CDCl3, 300 MHz):
δ 3.57
induced
photophysical
fluorescence
studies
quenching.
were corroborated
The
detailed
with
(s, 1 H), 3.90 (s, 3 H), 7.28-7.45 (m, 3 H), 7.66 (ddd, J = 8.3
Hz, J = 6.9 Hz, J = 1.5 Hz, 1 H), 7.74 (ddd, J = 8.4 Hz, J = 7.0
Hz, J = 1.5 Hz, 1 H), 8.03 (dd, J = 8.2 Hz, J = 1.2 Hz, 1 H),
8.12 (dd, J = 8.3 Hz, J = 1.2 Hz, 1 H), 8.48 (s, 1 H), 8.76-8.82
computations to rationalize the electronic structure and
the underlying electronic transitions responsible for the
spectroscopic effects.
recently, all four dyes additionally display a strong
emission in the solid state which we are currently
(m, 1 H). 13C NMR (CDCl3, 75 MHz):
(CH), 83.4 (Cquat), 109.4 (CH), 111.8 (Cquat), 121.4 (CH), 123.0
δ
33.4 (CH3), 82.3
Furthermore, as found only
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(2 CH), 127.4 (Cquat), 128.6 (CH), 128.8 (CH), 130.8 (CH), dichloromethane and filtered through a plug of basic
1
2
3
4
5
6
7
8
132.5 (CH), 135.5 (Cquat), 137.3 (Cquat) 139.1 (Cquat), 141.3
aluminium oxide to give the products 9.
(Cquat), 150.3 (Cquat). EI + MS (m/z (%)): 284 (20), 283 (M+,
General procedure for the four-component
synthesis of 3-aminovinylquinoxalines 9d,e,g-j (GP2).
The glyoxylic acid 2 (2.00 mmol) in dry 1,4-dioxane (5 mL)
was placed in a sintered screw-cap Schlenk tube under
nitrogen atmosphere and degassed with nitrogen (for
experimental details, see Table 6). Then, oxalyl chloride
(0.18 mL, 2.00 mmol, 1.0 equiv) was added dropwise to the
reaction mixture over the course of 1 min. The mixture
was first stirred at room temp (water bath, 5 min), and
then stirred at 50 °C (oil bath) for 4 h. Thereafter, the
mixture was cooled to room temp (water bath, 5 min).
Then, CuI (20 mg, 0.1 mmol, 5 mol %), trimethylsilyl
acetylene (2b) (0.28 mL, 2.00 mmol, 1.0 equiv.), and dry
triethylamine (0.59 mL, 4.20 mmol, 2.1 equivs) were
successively added to the reaction mixture, and stirring at
room temperature was continued for 15 h. Then,
methanol (2 mL), 1,2-diaminoarene 5 (2.00 mmol, 1.0
equiv), and acetic acid (0.23 mL, 4.00 mmol, 2.0 equivs.)
were successively added and the mixture was stirred at 50
°C for 1 h. Then, the cyclic secondary amine 8 (12.0 mmol,
6.0 equivs) was added and the reaction mixture was
stirred at room temp to 50°C to complete conversion. The
solvents were removed in vacuo, the remaining solid was
dissolved in dichloromethane and filtered through a plug
of basic aluminium oxide to give the products 9.
+
100), 282 (57), 232 (C16H14N2 , 4), 231 (11), 156 (11), 155 (14),
149 (15). IR: ν̃ 3267 (w), 3173 (w), 3051 (w), 2926 (w), 2091
(w), 1533 (s), 1477 (m), 1452 (m), 1422 (w), 1371 (m), 1337
(w), 1281 (w), 1240 (m), 1215 (m), 1192 (w), 1159 (w), 1121
(m), 1082 (m), 1051 (w), 1015 (w), 937 (m), 901 (w), 737 (s),
640 (m), 613 (m) [cm-1]. Anal. calcd. for C19H13N3 (283.3): C
80.54, H 4.62, N 14.81. Found: C 80.37, H 4.49, N 14.63.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Procedures
for
the
synthesis
of
3-
aminovinylquinoxalines 9
From terminal ethynylquinoxaline 7a. Terminal
ethynylquinoxaline 7a (142 mg, 0.50 mmol) was placed in
a reaction vessel with screw cap and dissolved in
tetrahydrofuran (1.25 mL, 2.5 mL/mmol) and 0.5 mL
methanol (1.0 mL/mmol). Then, 2.0 equivs pyrrolidine
(8a) (0.08 mL, 1.00 mmol) were added and the reaction
mixture was stirred at room temp for 1 h. Overlayering the
reaction mixture with n-pentane led to precipitation of
product 9a at -18 °C (ice box of the refrigerator). Filtration
and washing with n-pentane gave the analytically pure
product in 75% yield (133 mg, 0.375 mmol).
From TMS-protected ethynylquinoxaline 4a. TMS-
protected ethynylquinoxaline 6a (711 mg, 2.00 mmol) was
placed in a reaction vessel with screw cap and dissolved in
tetrahydrofuran (4.00 mL, 2.00 mL/mmol) and methanol
(2.00 mL, 1.00 mL/mmol). Then, 2.05 equivs of pyrrolidine
(8a) (0.33 mL, 4.10 mmol) were added and the reaction
mixture was stirred for at room temp for 1 h. Overlayering
the reaction mixture with n-pentane led to precipitation
of the product 9a at -18 °C. Filtration and washing with n-
pentane gave the analytically pure product in 83% yield
(589 mg, 1.66 mmol).
(E)-2-(1-Methyl-1H-indol-3-yl)-3-(2-(pyrrolidin-1-
yl)vinyl)quinoxaline (9a). Orange solid (522 mg, 73%), Mp
1
184 °C. H NMR (CDCl3, 600 MHz):
δ 1.83-1.93 (m, 4 H),
3.27 (br, 4 H), 3.87 (s, 3 H), 5.62 (d, J = 12.8 Hz, 1 H), 7.14-
7.24 (m, 1 H), 7.24-7.33 (m, 1 H), 7.35-7.46 (m, 2 H), 7.50-
7.58 (m, 1 H), 7.63 (s, 1 H), 7.78-7.84 (m, 1 H), 7.93 (d, J =
8.2 Hz, 2 H), 8.15 (d, J = 12.7 Hz, 1 H). 13C NMR (CDCl3, 75
MHz):
δ 25.2 (CH2), 33.0 (CH3), 49.2 (CH2), 94.0 (CH),
General procedure for the five-component
synthesis of 3-aminovinylquinoxalines 9a-c, 9f (GP1).
The π-nucleophile 1 (2.00 mmol) in dry THF (5 mL) was
placed in a sintered screw-cap Schlenk tube under
nitrogen atmosphere, degassed with nitrogen, and cooled
to 0 °C (water/ice, 5 min) (for experimental details, see
Table 6). Then, oxalyl chloride (0.18 mL, 2.00 mmol, 1.0
equiv) was added dropwise to the reaction mixture at 0 °C
over the course of 1 min. The mixture was first warmed to
room temp (water bath, 5 min), and then stirred at 50 °C
(oil bath) for 1 h. Thereafter, the mixture was cooled to
room temp (water bath, 5 min). Then, CuI (20 mg, 0.1
mmol, 5 mol %), trimethylsilyl acetylene (3a) (0.28 mL,
2.00 mmol, 1.0 equiv.), and dry triethylamine (0.59 mL,
4.20 mmol, 2.1 equivs) were successively added to the
reaction mixture, and stirring at room temperature was
109.4 (CH), 114.6 (Cquat), 120.0 (CH), 122.0 (CH), 122.1 (CH),
125.6 (CH), 126.9 (CH), 127.1 (Cquat), 128.4 (CH), 128.5 (CH),
130.2 (CH), 137.1 (Cquat), 139.5 (Cquat), 141.3 (Cquat), 142.9
(CH), 148.8 (Cquat), 152.9 (Cquat). EI + MS (m/z (%)): 355
(10), 354 (M+, 38), 353 (14), 286 (20), 285 (100), 284 ([M-
C4H8N]+, 74), 283 (21), 271 (14), 270 (15), 269 ([M-C4H8N-
CH3]+, 12). IR: ν
̃ 3051 (w), 2955 (w), 2930 (w), 2866 (w),
2851 (w), 1611 (m), 1537 (m), 1506 (m), 1483 (w), 1470 (w),
1456 (m), 1423 (w), 1383 (w), 1366 (m), 1339 (m), 1310 (m),
1275 (m), 1221 (m), 1184 (w), 1148 (w), 1117 (m), 1084 (m),
1030 (w), 1013 (m), 964 (m), 949 (m), 931 (m), 908 (w), 876
(w), 841 (w), 808 (w), 756 (m), 733 (s), 667 (w), 637 (w),
610 (m) [cm-1]. Anal. calcd. for C23H22N4 (354.5): C 77.94, H
6.26, N 15.81. Found: C 78.08, H 6.00, N 15.93.
continued for
6 h. Then, methanol (2 mL), 1,2-
diaminoarene 5 (2.00 mmol, 1.0 equiv), and acetic acid
(0.23 mL, 4.00 mmol, 2.0 equivs.) were successively added
and the mixture was stirred at 50 °C for 1 h. Then, the
cyclic secondary amine 8 (12.0 mmol, 6.0 equivs) was
added and the reaction mixture was stirred at room temp
to 50°C to complete conversion. The solvents were
removed in vacuo, the remaining solid was dissolved in
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Table 6. Experimental details of the one-pot four-step synthesis of 3-aminovinylquinoxalines 9 (GP1 and GP2).
1
2
Entry Starting material 1 or 2
1,2-Diamino arene 5
Secondary amine 8
3-Aminovinylquinoxaline 9
3
4
5
6
7
8
9
(yield)
1[a]
268 mg (2.00 mmol) of 1-
methyl indole (1a)
216 mg (2.00 mmol) of ortho-
phenylene diamine (5a)
0.96 mL (12.0 mmol)
of pyrrolidine (8a)
522 mg (73%) of 9a[b]
452 mg (74%) of 9b[b]
402 mg (60%) of 9c[b]
342 mg (57%) of 9d[b]
452 mg (69%) of 9e[b]
2[a]
3[a]
4[c]
5[c]
164 mg (2.00 mmol) of 1-
methyl pyrrole (1b)
216 mg (2.00 mmol) of 5a
216 mg (2.00 mmol) of 5a
216 mg (2.00 mmol) of 5a
216 mg (2.00 mmol) of 5a
0.96 mL (12.0 mmol)
of 8a
231 mg (2.00 mmol) of 2-
methoxy thiophene (1c)
0.96 mL (12.0 mmol)
of 8a
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
306 mg (2.00 mmol) of
phenyl glyoxylic acid (2a)
0.96 mL (12.0 mmol)
of 8a
319 mg (2.00 mmol) of 2-
thiophene glyoxylic acid
(2b)
0.96 mL (12.0 mmol)
of 8a
6[a]
268 mg (2.00 mmol) of (1a)
361 mg (2.00 mmol) of 1,2-
diamino 4,5-dichloro benzene
(5b)
0.96 mL (12.0 mmol)
of 8a
578 mg (68%) of 9f[d]
7[c]
8[c]
9[c]
10[c]
306 mg (2.00 mmol) of (2a)
319 mg (2.00 mmol) of (2b)
319 mg (2.00 mmol) of (2b)
306 mg (2.00 mmol) of (2a)
361 mg (2.00 mmol) of 5b
0.96 mL (12.0 mmol)
of 8a
382 mg (52%) of 9g[d]
486 mg (65%) of 9h[b]
439 mg (61%) of 9i[b]
361 mg (2.00 mmol) of 5b
0.96 mL (12.0 mmol)
of 8a
326 mg (2.00 mmol) of 2,3-
diamino naphthalene (5c)
0.96 mL (12.0 mmol)
of 8a
216 mg (2.00 mmol) of 5a
1.20 mL (12.0 mmol) of 270 mg (46%) of 9j[e]
piperidine (8b)
[a]According to GP1. [b]Reaction conditions for the amine addition step: 1 h, rt. [c]According to GP2. [d]Reaction conditions for the
amine addition step: h, 50°C.
h, 50°C. [e]Reaction conditions for the amine addition step:
1
2
(E)-2-(1-Methyl-1H-pyrrol-2-yl)-3-(2-(pyrrolidin-1-
yl)vinyl)quinoxaline (9b). Orange solid (452 mg, 74%), Mp
(br, 4 H), 3.97 (s, 3 H), 5.77 (d, J = 12.6 Hz, 1 H), 6.25 (d, J =
4.1 Hz, 1 H), 7.39 (ddd, J = 8.3 Hz, J = 6.9 Hz, J = 1.5 Hz, 1
H), 7.50 (d, J = 4.2 Hz, 1 H), 7.46-7.54 (m, 1 H), 7.70-75 (m,
1 H), 7.82 (dd, J = 8.2 Hz, J = 1.1 Hz, 1 H), 8.12 (d, J = 12.6
1
113 °C. H NMR (CDCl3, 300 MHz):
δ 1.86-2.02 (m, 4 H),
3.36 (br, 4 H), 3.78 (s, 3 H), 5.63 (d, J = 12.8 Hz, 1 H), 6.22
(dd, J = 3.7 Hz, J = 2.6 Hz, 1 H), 6.66 (dd, J = 3.7 Hz, J = 1.7
Hz, 1 H), 6.78 (dd, J = 2.5 Hz, J = 1.8 Hz, 1 H), 7.40 (ddd, J =
8.3 Hz, J = 6.9 Hz, J = 1.4 Hz, 1 H), 7.54 (ddd, J = 8.4 Hz, J =
6.9 Hz, J = 1.4 Hz, 1 H), 7.76 (ddd, J = 8.3 Hz, J = 1.4 Hz, J =
Hz, 1 H). 13C NMR (CDCl3, 75 MHz):
δ 25.3 (CH2), 49.4
(CH2), 60.2 (CH3), 93.1 (CH), 104.7 (CH), 126.0 (CH), 126.8
(CH), 126.9 (CH), 128.2 (CH), 128.7 (CH), 129.5 (Cquat),
139.0 (Cquat), 141.0 (Cquat), 143.5 (CH), 146.2 (Cquat), 151.0
(Cquat), 169.0 (Cquat). EI + MS (m/z (%)): 337 (M+, 7), 263
0.5 Hz, 1 H), 7.85 (ddd, J = 8.1 Hz, J = 1.4 Hz, J = 0.4 Hz, 1
(20), 262 ([M-C2H3OS]+, 100), 252 (10), 225 (11). IR: ν
̃ 3096
13
H), 8.08 (d, J = 12.8 Hz, 1 H). C NMR (CDCl3, 75 MHz):
δ
(w), 3057 (w), 2968 (w), 2932 (w), 2859 (w), 1614 (m), 1601
(m), 1547 (w), 1506 (m), 1491 (s), 1474 (m), 1458 (m), 1425
(s), 1377 (m), 1362 (m), 1341 (m), 1306 (m), 1277 (s), 1256
(m), 1244 (w), 1209 (s); 1184 (w), 1153 (m), 1130 (m), 1113
(m), 1061 (m), 1015 (w), 991 (w), 943 (m), 930 (m), 903 (w),
874 (w), 860 (w), 827 (w), 768 (m), 746 (s), 733 (m), 719
(m), 662 (w), 625 (w), 608 (m) [cm-1]. Anal. calcd. for:
C19H19N3OS (337.4): C 67.63, H 5.68, N 12.45, S 9.50.
Found: C 67.67, H 5.71, N 12.32, S 9.45.
25.2 (CH2), 35.5 (CH3), 49.2 (CH2), 93.0 (CH), 107.4 (CH),
112.3 (CH), 125.0 (CH), 125.6 (CH), 127.0 (CH), 128.5 (CH),
129.0 (CH), 130.1 (Cquat), 138.9 (Cquat), 141.2 (Cquat), 143.2
(CH), 146.1 (Cquat), 153.2 (Cquat). EI + MS (m/z (%)): 304
(M+, 35), 262 (12), 235 (20), 234 ([M-C4H8N]+, 100), 233
(39), 232 (60), 221 ([M-C5H9N]+, 19), 220 (19), 219 (11), 130
(22), 117 (13). IR (solid): ν̃ 2974 (w), 2945 (w), 2847 (w),
2357 (w), 1611 (s), 1603 (m), 1539 (m), 1510 (s), 1472 (m),
1456 (m), 1443 (m), 1423 (w), 1375 (s), 1364 (m), 1333 (m),
1312 (m), 1279 (s), 1246 (m), 1227 (m), 1211 (w); 1155 (w), 1130
(m), 1115 (m), 1090 (w), 1059 (m), 1034 (w), 1013 (w), 984
(m), 966 (m), 939 (m), 872 (m), 812 (w), 783 (m), 752 (s),
723 (s), 696 (m), 665 (m), 608 (m) [cm-1]. Anal. calcd. for
C19H20N4 (304.4): C 74.97, H 6.62, N 18.41. Found C 74.77,
H 6.58, N 18.25.
(E)-2-Phenyl-3-(2-(pyrrolidin-1-yl)vinyl)quinoxaline (9d).
Orange solid (342 mg, 57%), Mp 150 °C. H NMR (CDCl3,
1
300 MHz):
δ 1.83-1.95 (m, 4 H), 3.29 (br, 4 H), 5.27 (d, J =
12.7 Hz, 1 H), 7.37-7.53 (m, 4 H), 7.37 (ddd, J = 8.4 Hz, J =
6.9 Hz, J = 1.5 Hz, 1 H), 7.65-7.73 (m, 2 H), 7.80 (dd, J = 8.4
Hz, J = 1.0 Hz, 1 H), 7.92 (dd, J = 8.3 Hz, J = 1.2 Hz, 1 H),
8.09 (d, J = 12.7 Hz, 1 H). 13C NMR (CDCl3, 75 MHz):
(CH2), 49.2 (CH2), 93.2 (CH), 125.8 (CH), 127.0 (CH), 128.3
(CH), 128.5 (CH), 128.9 (CH), 129.0 (CH), 129.2 (CH), 139.2
(E)-2-(5-Methoxythiophen-2-yl)-3-(2-(pyrrolidin-1-
yl)vinyl)quinoxaline (9c). Red solid (402 mg, 60%), Mp 134
δ 25.2
1
°C. H NMR (CDCl3, 300 MHz):
δ 1.91-2.04 (m, 4 H), 3.42
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(Cquat), 139.6 (Cquat), 142.7 (Cquat), 142.9 (CH), 152.3 (Cquat), calcd. for C23H20Cl2N4 (423.3): C 65.25, H 4.76, N 13.22;
153.4 (Cquat). EI + MS (m/z (%)): 301 (M+, 48), 300 (12), 232
(45), 231 ([M-C4H8N]+, 100), 224 (29), 219 (12), 218 ([M-
C5H8N]+, 30), 149 (17), 116 (13), 96 (16), 84 (10), 83 (11), 77
(13), 72 (28), 71 (33), 70 (10), 57 (16), 56 (12), 55 (10). IR: ν
3057 (w), 2957 (w), 2853 (w), 1612 (m), 1522 (m), 1497 (w),
1475 (m), 1456 (w), 1441 (w), 1379 (m), 1364 (m), 1335 (m),
1298 (m), 1277 (m), 1252 (m), 1221 (w); 1179 (w), 1150 (m),
1113 (m), 1076 (w), 1034 (w), 1015 (m), 957 (m), 907 (w), 874
(w), 843 (w), 810 (w), 762 (s), 733 (w), 696 (s), 687 (m),
658 (w), 608 (m) [cm-1]. Anal. calcd. for: C20H19N3 (301.2):
C 79.70, H 6.35, N 13.94. Found: C 79.91, H 6.45, N 13.82.
Found: C 65.54, H 4.59, N 13.22.
1
2
3
4
5
6
7
8
(E)-6,7-dichloro-2-phenyl-3-(2-(pyrrolidin-1-
yl)vinyl)quinoxaline (9g). Dark-red solid (382 mg, 52%),
1
̃
Mp 164 °C. H NMR (CDCl3, 300 MHz):
δ 1.86-2.00 (m, 4
H), 3.32 (s, 4 H), 5.24 (d, J = 12.5 Hz, 1 H), 7.39-7.56 (m, 3
H), 7.59-7.74 (m, 2 H), 7.88 (s, 1 H), 7.98 (s, 1 H), 8.13 (d, J
= 12.2 Hz, 1 H). 13C NMR (CDCl3, 75 MHz):
δ 25.2 (CH2),
47.8-50.7 (CH2), 92.8 (CH), 127.3 (CH) 128.4 (CH), 128.85
(CH), 128.93 (CH), 129.0 (Cquat), 129.5 (CH), 133.3 (Cquat),
137.9 (Cquat), 138.9 (Cquat), 144.2 (CH), 153.0 (Cquat), 154.6
(Cquat). EI + MS (m/z (%)): 371 ([M{37Cl,35Cl}]+, 26), 370
(16), 369 ([M{35Cl,35Cl}]+, 39), 368 (12), 303 ([M{37Cl,37Cl}-
C4H8N]+, 16), 302 (35), 301 ([M{37Cl,35Cl}-C4H8N]+, 70), 300
(56), 299 ([M{35Cl,35Cl}-C4H8N]+, 100), 294 ([M{37Cl,35Cl}-
C6H5]+, 17), 292 ([M{35Cl,35Cl}-C6H5]+, 26), 288
([M{37Cl,35Cl}-C5H9N]+,16), 287 (13), 286 ([M{35Cl,35Cl}-
C5H9N]+, 22), 264 (18), 150 (12), 96 (C6H10N+, 18), 84 (13), 70
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(E)-2-(2-(Pyrrolidin-1-yl)vinyl)-3-(thiophen-2-yl)quinoxaline
(9e). Red solid (452 mg, 69%), Mp 135 °C. 1H NMR (CDCl3,
300 MHz):
δ 1.83-2.09 (m, 4 H), 3.24-3.60 (br, 4 H), 5.75
(d, J = 12.6 Hz, 1 H), 7.15 (dd, J = 5.1 Hz, J = 3.6 Hz, 1 H),
7.42 (ddd, J = 8.3 Hz, J = 6.9 Hz, J = 1.4 Hz, 1 H), 7.48 (dd, J
= 5.1 Hz, J = 1.0 Hz, 1 H), 7.55 (ddd, J = 8.4, Hz, J = 6.9 Hz, J
= 1.5 Hz, 1 H), 7.73 (dd, J = 3.7 Hz, J = 1.1 Hz, 1 H), 7.75-7.84
(br, 1 H), 7.84-7.93 (m, 1 H), 8.17 (d, J = 12.6 Hz, 1 H). 13C
(11). IR: ν̃ 2953 (w), 2851 (w), 1609 (m), 1539 (w), 1516 (s),
1506 (s), 1495 (m), 1477 (m), 1452 (m), 1443 (m), 1416 (w),
1371 (m), 1333 (m),1312 (m), 1302 (m), 1277 (m), 1260 (m),
1244 (m), 1219 (m), 1207 (m), 1180 (w), 1146 (s), 1103 (m),
1076 (m), 1036 (m),1013 (m), 999 (m), 978 (m), 959 (m),
920 (m), 908 (w), 885 (m), 860 (m), 810 (m), 773 (m), 760
(m), 719 (m), 696 (s), 675 (m), 650 (m), 631 (m) [cm-1].
Anal. calcd. for C20H17Cl2N3 (370.3): C 64.88, H 4.63, N
11.35; gef.: C 64.80, H 4.55, N 11.23.
NMR (CDCl3, 75 MHz):
δ 25.3 (CH2), 48.5-50.2 (CH2), 92.8
(CH), 126.0 (CH), 126.8 (CH), 127.3 (CH), 127.9 (CH), 128.1
(CH), 128.7 (CH), 129.4 (CH), 139.0 (Cquat), 141.4 (Cquat),
142.8 (Cquat), 143.8 (CH), 146.4 (Cquat), 151.5 (Cquat). EI + MS
(m/z (%)): 308 (15), 307 (M+, 70), 306 (16), 274 (15), 262
(11), 239 (13), 238 (52), 237 ([M-C4H8N]+, 100), 224 ([M-
C5H9N]+, 22), 205 (11). IR: ν
̃ 3073 (w), 2963 (w), 1612 (s),
1599 (s), 1509 (s), 1504 (s), 1476 (m), 1452 (m), 1425 (m),
1377 (s), 1360 (m), 1341 (m), 1331 (m), 1288 (m), 1277 (s),
1219 (m), 1152 (m), 1111 (m), 1072 (m), 1015 (m), 957 (m),
937(w), 761 (s), 750 (s), 738 (s), 710 (s), 608 (s) [cm-1]. Anal.
calcd. for: C18H17N3S (307.4): C 70.35, H 5.57, N 13.67, S
10.43. Found: C 70.23, H 5.63, N 13.47, S 10.37.
(E)-6,7-dichloro-2-(2-(pyrrolidin-1-yl)vinyl)-3-(thiophen-2-
yl)quinoxaline (9h). Red solid (486 mg, 65%), Mp 163 °C.
1H NMR (CDCl3, 300 MHz):
δ 1.85-2.08 (m, 4 H), 3.41 (br, 4
H), 5.71 (d, J = 12.5 Hz, 1 H), 7.14 (dd, J = 5.1 Hz, J = 3.7 Hz, 1
H), 7.49 (dd, J = 5.1 Hz, J = 1.1 Hz, 1 H), 7.74 (dd, J = 3.7 Hz,
J = 1.1 Hz, 1 H), 7.81 (s, 1 H), 7.94 (s, 1 H), 8.15 (d, J = 12.5
Hz, 1 H). 13C NMR (CDCl3, 75 MHz):
δ 25.3 (CH2), 47.0-
(E)-6,7-dichloro-2-(1-methyl-1H-indol-3-yl)-3-(2-(pyrrolidin-
1-yl)vinyl)quinoxaline (9f). Red solid (578 mg, 68%), Mp
53.0 (CH2), 92.5 (CH), 127.3 (CH), 127.4 (CH), 128.4 (CH),
128.5 (CH), 129.1 (CH), 129.2 (Cquat), 133.1 (Cquat), 137.7
(Cquat), 140.5 (Cquat), 142.5 (Cquat), 144.6 (CH), 147.3 (Cquat),
152.3 (Cquat). EI + MS (m/z (%)): 378 (10), 377 (M{37Cl,
35Cl}+, 44), 376 (21), 375 (M{35Cl, 35Cl}+, 61), 374 (13), 344
(10), 342 (16), 309 ([M{37Cl, 37Cl}-C4H8N]+, 21), 308 (44),
307 ([M{37Cl, 35Cl}-C4H8N]+, 80), 306 (68), 305 ([M{35Cl,
35Cl}-C4H8N]+, 100), 294 ([M{37Cl, 35Cl}-C5H9N]+, 15), 292
([M{35C, 35Cl}-C5H9N]+, 21), 273 (13), 269 (11), 153 (10), 96
1
156 °C. H NMR (CDCl3, 300 MHz):
δ 1.82-2.01 (m, 4 H),
3.30 (br, 4 H), 3.88 (s, 3 H), 5.61 (d, J = 12.6 Hz, 1 H), 7.21
(ddd, J = 8.0 Hz, J = 7.0 Hz, J = 1.2 Hz, 1 H), 7.30 (ddd, J =
8.1 Hz, J = 6.9 Hz, J = 1.2 Hz, 1 H), 7.39 (d, J = 8.1 Hz, 1 H),
7.64 (s, 1 H), 7.85 (s, 1 H), 7.97 (s, 1 H), 7.97 (d, J = 7.9 Hz, 1
13
H), 8.16 (d, J = 12.8 Hz, 1 H). C NMR (CDCl3, 75 MHz):
δ
25.2 (CH2), 33.1 (CH3), 48.0-50.28 (br, CH2), 93.7 (CH),
109.5 (CH), 114.0 (Cquat), 120.3 (CH), 122.0 (CH), 122.4 (CH),
127.0 (Cquat), 127.4 (CH), 128.7 (Cquat), 129.0 (CH), 130.6
(CH), 132.0 (Cquat), 137.2 (Cquat), 138.3 (Cquat), 140.2 (Cquat),
144.0 (CH), 150.0 (Cquat), 153.6 (Cquat). EI + MS (m/z (%)):
424 (M+{37Cl, 35Cl}, 10), 422 (M+{35Cl, 35Cl}, 15), 357 (10), 356
([M{37Cl, 37Cl}-C4H8N]+, 18), 355 (62), 354 ([M{37Cl, 35Cl}-
C4H8N]+, 57), 353 (100), 352 ([M{35Cl, 35Cl}-C4H8N]+, 65),
351 (12), 340 (12), 339 ((M{37Cl, 35Cl}-C4H8N-CH3)+, 18), 338
(14), 337 ([M{35Cl, 35Cl}-C4H8N-CH3]+, 12), 169 (11), 206 (14),
(C6H10N+, 16), 70 (C4H8N+, 18). IR: ν
̃ 2967 (w), 2853 (w),
1609 (s), 1508 (s), 1504 (s), 1474 (m), 1454 (s), 1433 (m), 1371
(s), 1364 (s), 1338 (m), 1327 (m), 1312 (m), 1281 (s), 1260 (m),
1234 (s), 1219 (s), 1198 (m), 1138 (s), 1113 (s), 1105 (s), 1084
(m), 1059 (m), 984 (m), 962 (m), 908 (w), 883 (m), 872 (s),
856 (m), 849 (m), 802 (w), 777 (w), 762 (m), 731 (s), 723
(s), 702 (m), 679 (w), 652 (w) [cm-1]. HR-MS (ESI) calcd.
for C18H1535Cl2N3S+H+: 376.0437; Found: 376.0438.
156 (12), 155 (15). IR: ν̃ 2976 (w), 2953 (w), 2927 (w), 2903
(E)-2-(2-(pyrrolidin-1-yl)vinyl)-3-(thiophen-2-
(w), 2874 (w), 2851 (w), 1605 (m), 1530 (m), 1506 (s), 1479
(m), 1454 (m), 1427 (w), 1381 (m), 1362 (m), 1337 (m), 1306
(m), 1279 (m), 1258 (m), 1238 (m), 1219 (w), 1209 (m), 1186
(m), 1171 (m), 1153 (m), 1101 (m), 1084 (m), 1036 (m), 1018
(w), 986 (m), 966 (m), 951 (m), 928 (m), 908 (w), 883 (s),
808 (w), 750 (m), 739 (s), 673 (m), 654 (m) [cm-1]. Anal.
yl)benzo[g]quinoxaline (9i). Violet solid (439 mg, 61%),
1
Mp 150 °C. H NMR (CDCl3, 300 MHz):
δ 1.90-2.05 (m, 4
H), 3.42 (br, 4 H), 5.79 (d, J = 12.5 Hz, 1 H), 7.17 (dd, J = 5.1
Hz, J = 3.7 Hz, 1 H), 7.34-49 (m, 2 H), 7.51 (dd, J = 5.1 Hz, J
= 1.1 Hz, 1 H), 7.79 (dd, J = 3.7 Hz, J = 1.1 Hz, 1 H), 7.92-8.00
(m, 2 H), 8.24 (2, 1 H), 8.27 (d, J = 12.5 Hz, 1 H), 8.43 (s, 1
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The Journal of Organic Chemistry
= 8.0 Hz, 1 H), 10.13 (d, J = 12.4 Hz, 1 H), 15.05 (br, 1 H). 13C
NMR (CDCl3, 75 MHz): 24.7 (CH2), 24.8 (CH2), 33.3
H). 13C NMR (CDCl3, 75 MHz):
δ 25.3 (CH2), 47.7-50.7
1
2
3
4
5
6
7
8
(CH2), 93.3 (CH), 123.3 (CH), 124.8 (CH), 126.1 (CH), 126.8
(CH), 127.3 (CH), 127.8 (CH), 128.3 (CH), 128.4 (CH), 128.6
(CH), 131.9 (Cquat), 134.3 (Cquat), 137.0 (Cquat), 138.6 (Cquat),
142.9 (Cquat), 144.4 (CH), 148.6 (Cquat), 151.6 (Cquat). EI + MS
(m/z (%)): 358 (15), 357 (M, 60), 356 (20), 324 (13), 312 (15),
289 (17), 288 (64), ([M-C4H8N]+, 81), 278 (11), 276 (23), 275
(18), 274 ([M-C5H9N]+, 28), 262 (36), 255 (11), 250 (11), 179
δ
(CH3), 47.6 (CH2), 53.9 (CH2), 89.3 (CH), 110.0 (CH), 112.6
(Cquat), 118.6 (CH), 120.8 (CH), 121.5 (CH), 122.9 (CH), 126.2
(Cquat), 126.6 (CH), 128.4 (CH), 129.5 (Cquat), 131.09 (CH),
131.13 (CH), 137.2 (2 Cquat), 145.6 (Cquat), 151.9 (Cquat), 154.8
(Cquat). MALDI-MS (m/z): 355.4 [MH+-Cl]. IR: ν
̃ 3127 (w),
3078 (w), 3034 (w), 2957 (w), 2916 (w), 2872 (w), 2673 (w),
1599 (s), 1528 (s), 1491 (m), 1476 (m), 1458 (m), 1406 (s),
1379 (m), 1364 (s), 1342 (s), 1331 (m), 1273 (s), 1261 (m); 1234
(s), 1182 (m), 1161 (m), 1128 (m), 1111 (m), 1088 (m), 1013 (w),
991 (w), 947 (m), 932 (w), 897 (m), 860 (m), 802 (w), 765
(s), 756 (s), 739 (s), 664 (w), 638 (w) [cm-1]. Anal. calcd.
for: C23H23ClN4 · 1/3 H2O (390.9 + 6.01): C 69.60, H 6.01,
N 14.12. Found: C 69.44, H 5.76, N 13.98.
(14), 127 (14), 126 (60), 88 (100), 43 (11). IR: ν̃ 2969 (w),
9
2864 (w), 1672 (w), 1600 (s), 1528 (m), 1514 (s), 1499 (s),
1474 (m), 1454 (m), 1422 (m), 1396 (s), 1364 (s), 1354 (s),
1341 (s), 1315 (m), 1272 (s), 1261 (s), 1242 (s), 1225 (m), 1148
(s), 1130 (m), 1109 (s), 1080 (m), 1045 (m), 972 (m), 916 (m),
873 (s), 864 (s), 852 (m), 802 (m), 770 (m), 735 (s), 708 (s),
604 (m) [cm-1]. Anal. calcd. for: C22H19N3S (357.5): C 73.92,
H 5.36, N 11.75, S 8.97. Found: C 73.86, H 5.50, N 11.79, S
8.92.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
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ASSOCIATED CONTENT
Supporting Information. Crystall structure determination
data of compound 9a. Experimental details on the optimiza-
tion studies, spectroscopic data and NMR spectra of com-
pounds 7a, 9, and 9a-H+, Stokes shift - ꢀꢁꢂ-plot, computa-
tional data of compounds 9a-9d, and 9a-H+. This material is
available free of charge via the Internet at
http://pubs.acs.org.
(E)-2-phenyl-3-(2-(piperidin-1-yl)vinyl)quinoxaline
(9j).
Red-brown solid (270 mg, 46%), Mp 184 °C. H NMR
(CDCl3, 300 MHz): 1.60 (s, 6 H), 3.21 (br, 4 H), 5.44 (d, J
1
δ
= 12.9 Hz, 1 H), 7.41-7.53 (m, 4 H), 7.58 (ddd, J = 8.4 Hz, J =
6.9 Hz, J = 1.5 Hz, 1 H), 7.62-7.73 (m, 2 H), 7.77-7.92 (m, 2
H) ,7.91 (dd, J = 8.2 Hz, J = 1.4 Hz, J = 0.6 Hz, 1 H). 13C
NMR (CDCl3, 75 MHz):
δ 24.1 (CH2), 25.4 (CH2), 49.8
(CH2), 92.2 (CH), 126.0 (CH), 127.1 (CH), 128.4 (CH), 128.5
(CH), 128.9 (CH), 129.1 (CH), 129.3 (CH), 139.5 (Cquat), 142.0
(Cquat), 146.6 (CH), 152.4 (Cquat), 153.5 (Cquat). EI + MS (m/z
(%)): 316 (17), 315 (M+, 72), 314 (24), 239 (12), 238 ([M-
C6H5]+, 73), 231 ([M-C5H10N]+, 100), 219 (17), 218 ([M-
AUTHOR INFORMATION
Corresponding Author
* ThomasJJ.Mueller@uni-duesseldorf.de
* Ute.Resch@bam.de
C6H11N]+, 21), 120 (11). IR: ν
̃ 3055 (w), 2940 (w), 2920 (w),
Author Contributions
2851 (w), 1607 (s), 1574 (m), 1520 (s), 1506 (m), 1493 (m),
1441 (m), 1385 (s), 1368 (m), 1325 (m), 1287 (m), 1279 (m),
1244 (s), 1200 (m), 1165 (m), 1155 (m), 1109 (s), 1074 (m),
1030 (m), 997 (m), 974 (m), 937 (m), 920 (m), 905 (m),
883 (w), 853 (m), 766 (m), 750 (s), 735 (m), 700 (s), 684
(m), 667 (m), 621 (s) [cm-1]. Anal. calcd. for C21H21N3
(315.4): C 79.97, H 6.71, N 13.32; Found: C 80.17, H 6.62, N
13.16.
The manuscript was written through contributions of all
authors. All authors have given approval to the final version
of the manuscript.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
The financial support of the Deutsche Forschungsgemein-
schaft DFG (Mu 1088/9-1) and the Fonds der Chemischen
Industrie is gratefully acknowledged. The authors cordially
thank Dr. Bernhard Mayer for experimental assistance and
discussion. This work is dedicated on the occasion of the 70th
birthday of Prof. Dr. Klaus Müllen.
Protonation of 9a. 3-Aminovinyl quinoxaline 9a (177
mg, 0.50 mmol) was placed in a reaction vessel with screw
cap and dissolved in tetrahydrofurane (1.25 mL) and
methanol (0.5 mL). Then, hydrochloric acid (1 mL, 37 %,
12.1 mmol) was added to give a dark violet suspension and
the reaction mixture was stirred for 1 h at room temp.
Thereafter, a red precipitate formed upon the addition of
10 mL of water. The solid was extracted with
dichloromethane. The combined organic layers were
dried with anhydrous sodium sulfate and the solvents was
removed in vacuo to give compound 9a-H+ (0.193 mg,
98%).
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