Solvatochromic fluorescent 2-substituted 3-ethynyl quinoxalines: Four-component synthesis, photophysical properties, and electronic structure

Article abstract of DOI:10.1021/jo4025978

2-Substituted 3-ethynylquinoxalines can be rapidly synthesized in generally excellent yields by a consecutive four-component synthesis starting from electron-rich π-nucleophiles, oxalyl chloride, terminal alkynes, and 1,2-diaminoarenes. The title compound

Full text of DOI:10.1021/jo4025978

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Solvatochromic Fluorescent 2‑Substituted 3‑Ethynyl Quinoxalines:
Four-Component Synthesis, Photophysical Properties,
and Electronic Structure
Charlotte F. Gers,† Jan Nordmann,† Ceyda Kumru,† Walter Frank,‡ and Thomas J. J. Muller*,†
̈
‡
†Institut fur Organische Chemie und Makromolekulare Chemie and Institut fur Anorganische Chemie und Strukturchemie,
̈
̈
Heinrich-Heine Universitat Dusseldorf, Universitatstrasse 1, D-40225 Dusseldorf, Germany
̈
̈
̈
̈
S
* Supporting Information
ABSTRACT: 2-Substituted 3-ethynylquinoxalines can be
rapidly synthesized in generally excellent yields by a
consecutive four-component synthesis starting from electron-
rich π-nucleophiles, oxalyl chloride, terminal alkynes, and 1,2-
diaminoarenes. The title compounds are highly fluorescent
with a pronounced emission solvatochromism. The photo-
physical properties and electronic structure were additionally
corroborated by computations on the DFT level of theory.
properties.12 For instance, Kudo et al. reported the synthesis of a
quinoxaline-based push−pull system, which was found to
quantitatively screen protein binding-site polarity of bovine
serum albumine as a consequence of its pronounced emission
solvatochromism.13 Lin et al. synthesized a set of chromophores
based upon 2,3,5-trisubstituted quinoxaline cores, which display
two-photon absorption properties.14 Faust et al. synthesized
related 2,3-bisethynylquinoxalines through the condensation of
dialkynyl-1,2-diones and 1,2-diaminoarenes.15 Their acetylenic
quinoxalinoporphyrazine derivatives are potential candidates as
photosensitizers in photodynamic therapy.16
We have recently reported a straightforward and modular
one-pot approach to the densely functionalized but yet
scarcely explored class of ynediones, starting from electron-rich
π-nucleophiles, oxalyl chloride, and terminal alkynes (Scheme 1,
path 1).17 The sequence starts with a Lewis acid free Friedel−
Crafts acylation of the π-nucleophile with oxalyl chloride. The
generated glyoxyl chloride is directly converted into the ynedione
by applying a Cu(I)-catalyzed Stephens−Castro alkynylation.
The employment of CuI as the single catalyst is crucial for the
success of the ynedione formation as the Pd/Cu-catalyzed
Sonogashira protocol18 leads to decarbonylation and eventually
to the formation of ynones.19 Furthermore, the Cu(I)-catalyzed
variant20 does not require complex ligands. An alternative route
to ynediones starts from glyoxylic acids and oxalyl chloride and
the subsequent transformation of the glyoxyl chloride with
alkynes (Scheme 1, path 2).21 Both methodologies allow for the
introduction of a wide range of substituents to the ynedione core.
INTRODUCTION
■
Over the past two decades, organic electronics have grown to
an important field of interest in academia as well as in industry,
providing crucial advantages over silicon-based electronics, such
as low cost, flexibility, and functionality.1 Due to the constant
demand for novel tailor-made functional π-systems, new and
reliable accesses toward such compounds have to be
established. Diversity-oriented syntheses (DOS) are highly
advantageous for synthetically exploring structural and func-
tional characteristics because variation of the individual
components leads to a heterogenic product library.2 Among
DOS, multicomponent reactions (MCRs)3 and one-pot strategies
are economically and ecologically favorable, since higher resource
efficiency is combined with lower waste production in comparison
to traditional multistep synthesis.4 The concatenation of transition-
metal-catalyzed reactions in one-pot processes as the liaison of
their unique reactivity patterns with fundamental organic reactivity
allows for convenient accesses to reactive intermediates and their
in situ conversion.5 While MCR approaches have regularly been
employed in syntheses of natural products, pharmaceutically
interesting compounds,6 and in combination with high-throughput
screening in medicinal chemistry, their full potential in the field of
functional π-systems just has begun to be exploited.2a,b Most
rewardingly, MCRs are ideally suited for rationally designing
compound libraries for studying structure−property relationships.
Among myriad nitrogen-containing heterocycles that are
ubiquitous in natural products and biological active com-
pounds7 as well as structural units in functional π-systems,8
quinoxalines are particularly interesting. Many derivatives possess
antitubercular,9 antibiotic,10 and anticancer activity,11 and more-
over, they are constantly studied due to their photophysical
Received: November 22, 2013
© XXXX American Chemical Society
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Scheme 1. Two One-Pot Routes to Ynediones via Glyoxyl
Intermediates
RESULTS AND DISCUSSION
■
Synthesis. First optimization studies of the three-
component ynedione synthesis with respect to substrate
concentration, temperature, solvent, and reaction times were
carried out on our previously used model system17 consisting of
N-methylindole (1a) and phenylacetylene (2a) furnishing the
ynedione 3a (Table 1).
The original conditions for the steps of the glyoxylation−
alkynylation sequence17 at room temperature required 4 and
24 h, respectively (Table 1, entry 1). By raising the temperature
Table 1. Optimization Study for the Synthesis of Ynedione 3a
Ynediones are highly valuable intermediates for the synthesis
of various heterocyclic systems,22 and we have illustrated that
both the Michael system or the dione motif can be addressed in
the final step of a consecutive one-pot sequence.17 For instance,
phenylamidine selectively reacts with the Michael acceptor
furnishing a 4-acylpyrimidine, whereas 1,2-diaminobenzene
exclusively addresses the dione motif to form a 2-substituted
3-ethynylquinoxaline (Scheme 2).
glyoxylation
solvent
coupling
c0(1a)
(M)
T
t1
c0(2a)
t2
(h)
ynedione
b
a
entry
(°C) (h)
(M)
3a (%)
1
2
3
4
5
6
7
0.2
0.2
0.4
0.4
0.4
0.4
0.4
THF
rt
50
50
50
rt
4
1
1
1
1
1
1
0.2
0.2
0.4
0.4
0.4
0.4
0.4
24
6
64
63
69
61
67
38
56
Scheme 2. Retrosynthetic Convergence of 4-Acylpyrimidines
and 2-Substituted 3-Ethynylquinoxalines to Ynediones
THF
THF
6
4
THF
1,4-dioxane
CH2Cl2
6
rt
6
1,2-
dichloroethane
rt
6
a
b
All reactions were performed on a 2.00 mmol scale. Yields after
chromatography on silica gel.
for the glyoxylation step to 50 °C (Table 1, entry 2) and
simultaneously increasing the concentration of 1a and 2a the
reaction times of both steps were reduced to 1 and 6 h,
respectively, while the yield slightly improved (Table 1, entry 3).
However, further shortening of the reaction time resulted in a
decreased yield (Table 1, entry 4). In addition, we found that 1,4-
dioxane can be equally well used as solvent (Table 1, entry 5),
whereas dichloromethane and 1,2-dichloroethane give lower yields
(Table 1, entries 6 and 7).
With these optimized conditions (Table 1, entry 3) for the
ynedione formation in hand and the time for the terminal
cyclocondensation reduced from 3 h17 to 1 h, the consecutive four-
component synthesis of 3-ethynylquinoxaline 5a was performed in
a total reaction time of 8 h (cf. 31 h)17 and with slightly improved
yields from 72%17 to now 80% (Scheme 3).
Surprisingly, ethynylquinoxalines have only been scarcely
studied. Ames et al. reported a Sonogashira-type reaction of
2-chloroquinoxaline with terminal alkynes to give 2-ethynylqui-
noxalines as precursors for the synthesis of pyrido[l,2-a]-
quinoxalin-4-ones.23 To our knowledge, only one ring-forming
synthesis of 2-(hetero)aryl-substituted 3-ethynylquinoxalines
has been reported so far,24 where 1,2-diaminobenzene is reacted
with two molecules of a terminal alkyne under Cu(I)-catalysis.
However, this methodology can only generate 2-substituted
3-ethynylquinoxalines, which have identical substituents for R1
and R2.
Furthermore, we discovered via the naked eye that the
2-substituted 3-ethynylquinoxalines are highly fluorescent both
in solution and in the solid state. In addition, test tube experiments
indicated a pronounced emission solvatochromism.25 The solvent-
polarity sensitivity of solvatochromic fluorophores has found wide
application in studies on protein biochemistry.26
Scheme 3. Optimized Conditions for the Four-Component
Synthesis of 3-Ethynylquinoxaline 5a
Since our multicomponent entry toward 2-(hetero)aryl-sub-
stituted 3-ethynylquinoxalines allows for a high degree of structural
and functional variation due to its toolbox conception, we became
intrigued to further explore this potential to luminescent derivatives.
Here, we report the improved three-component synthesis of
fluorescent 3-ethynylquinoxalines through a glyoxylation−
Stephens−Castro coupling, as well as a study of the photophysical
properties and electronic structure of this substance class.
The optimized conditions were applied in the four-component
synthesis of various 3-ethynylquinoxalines 5 with different
substitution patterns (Scheme 4, Table 2). Much to our delight,
the sequence represents a modular approach to a substance library
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A closer analysis of the crystallographic data revealed the
strong tendency of the molecules to build up pairs in the solid
state, which are mostly caused by π−π-interactions (Figure 1,
left). These pairs are arranged in columns, which resemble a
herringbone pattern (Figure 1, right).
Scheme 4. Consecutive Four-Component Synthesis of
3-Ethynylquinoxalines 5 with Glyoxylation−Alkynylation−
Cyclocondensation Sequence
Within the pairs, the angle between the best planes of the π-
systems in close contact, namely the six-membered ring of the
anisole fragment and the neighboring quinoxaline fragment, is
7.4°. The distances between the atoms of the six-membered
ring of the anisole fragment to the best plane of the quinoxaline
fragment range from 329.3(2) to 356.9(2) pm, the center of the
six-membered ring being 338.6(2) pm apart from that plane.
Between the pairs, the closest π-system contact involves the
above-mentioned anisole fragment and the indole fragment of a
neighboring pair. The angle between the best planes of the six-
membered ring of the anisole fragment and the five-membered
ring of the indole fragment is 12.8°. Individual distances of the
atoms of the five-membered ring to the best plane of the six-
membered ring are in the range 340.1(2) to 371.5(3) pm, i.e.,
π−π-contacts within the pairs are significantly closer than
between pairs.
Photophysical Properties. The photophysical properties
of five selected 2-heteroaryl-substituted 3-ethynylquinoxalines 5
were thoroughly studied by UV/vis and fluorescence spectroscopy
(Table 4). The structures were chosen as two consanguineous
series to study the effects of the 2-substituent of the quinoxaline core
(compounds 5a, 5m, 5r) as well as the influence of the electronic
nature of the aryl ethynyl group (compounds 5a, 5d, 5h).
Additionally, the emission solvatochromism of compound 5d
was investigated. The relative fluorescence quantum yields ΦF
were determined with coumarin 15329 as standard according to
literature procedures.30
in moderate to excellent yields. The components π-nucleophile 1,
alkyne 2, and 1,2-diaminoarene 4 can be varied within a wide
range, and it is noteworthy to mention that all four components
are applied in strictly equimolar ratios.
Aryl- (5a, 5d−i) as well as silyl-substituted alkynes (5b,c)
can be successfully employed in the synthesis, whereas aliphatic
alkynes only sluggishly undergo the Stephens−Castro coupling
step. The π-nucleophile can vary from 1-methylindole (5a),
differently N-substituted pyrroles (5j−o), and 2-methoxythiophene
(5p−r) to azulene (5s). Expectedly, the initial glyoxylation, i.e., an
electrophilic substitution reaction, regioselectively occurs for indoles
at the 3-position for pyrroles at the 2-position with the exception of
N-TIPS-pyrrole (5o) for steric reasons. Although the nucleophil-
icity of the substrates slightly differs according to Mayr’s scale,27 all
glyoxylations reach full conversion at 50 °C. It is noteworthy to
mention that a further increase of the reaction temperature does
not improve the yields. In the final cyclocondensation step,
the employed 1,2-diaminoarenes 4 react equally well for the
4,5-dichloro (5t) and 4-nitro derivative (5u) as well as
2,3-diaminopyridine (5v) giving good yields. However, 1,2-diamino-
4-nitrobenzene (4c) and 2,3-diaminopyridine (4d) give
mixtures of regioisomers due to the different nucleophilicities
of the amino nitrogen atoms. Based upon electronic effects of
the substituents on both the dione and the diamine motif the
major isomer presumably arises from the attack of the more
nucleophilic amino group at the alkynyl conjugated carbonyl
group. Additionally, 2,3-diaminonaphthalene (4e) furnishes
benzo[g]quinoxalines (5w,x) with lower yields, which can be
rationalized by the poor solubility of the products, which effects
a complicated work up procedure.
In the UV/vis absorption spectra three to four distinct, broad,
structureless maxima can be found, and the longest wavelength
bands appear between λmax = 418 and 393 nm with molar
absorption coefficients ε ranging from 8000 to 14600 L/mol·cm
(Figure 2).
The remote arylethynyl substituent has only a minor effect
on the position of this absorption band and varies from λmax
=
408 (methoxy, compound 5d) over 411 (hydrogen, compound
5a) to 418 nm (cyano, compound 5h). For the 2-substituent
this effect is more pronounced. In the consanguineous series of
compounds 5d, 5m, and 5r, where the anisylethynyl substituent
in 3-position is kept constant, the 1-methylindole (5d) and the
2-methoxythienyl (5r) derivative behave very similarly, whereas
the more electron-rich 1-phenylpyrrolyl substituent of com-
pound 5m results in a blue shift of the longest wavelength
absorption band to λmax = 393 nm.
A similar picture emerges from the comparison of the
emission spectra, where the structureless shortest wavelength
emission band ranges between λmax = 474 and 520 nm. By
increasing the electron-withdrawing character of the remote
arylethynyl substituent the emission maximum is red-shifted
from λmax = 506 (5d) over 510 (5a) to 520 nm (5h). While the
position of the emission bands of 5d and 5r at 506 and 508 nm,
respectively, are almost identical, the luminescence of the
pyrrole derivative 5m is hypsochromically shifted to 474 nm.
The Stokes shifts can be found in a narrow range between
4700 and 4800 cm−1, except for the 1-phenyl pyrrole
derivative 5m, which is with 4400 cm−1 slightly smaller. The
fluorescence quantum yields ΦF of the 1-methylindole-
substituted derivatives 5a, 5d, and 5h are hardly affected
by the variation of the alkynyl substituent and lie between
While the glyoxylation approach is limited to electron-rich
heterocycles at the 2-position of the quinoxalines due to the
initial electrophilic glyoxylation, we expanded the scope of the
substitution pattern by initiating the ynedione formation through
activation−Stephens−Castro coupling (see Scheme 1, path 2).
This approach also enables the introduction of electroneutral
substituents at position 2 of the 3-ethynylquinoxalines 7 starting
from glyoxylic acids 6 in the sense of a three-component
activation−Stephens−Castro coupling−cyclocondensation se-
quence in moderate to good yields (Scheme 5, Table 3).
The molecular structures of the 3-ethynylquinoxalines 5 and
7 were unambiguously supported by 1H and 13C NMR
spectroscopy, mass spectrometry, and combustion analysis. Later,
the structures were additionally corroborated by X-ray diffraction
analysis of compounds 5d, 5n, 5q, and 5x.28 Expectedly, in the
solid state the quinoxaline core and the arylethynyl substituent are
coplanarily alligned in all cases. However, the torsion angle between
the 2-substituent and the quinoxaline core varies with the steric bulk
of this substituent. For the 2-methoxythienyl derivative 5q
both moieties are almost coplanarily alligned, while for the
1-methylindole derivatives 5d and 5x this substituent is slightly
twisted out of coplanarity by 13.2 and 16.2°, respectively. For the
1-phenylpyrrole substituent in compound 5q, this torsion increases
to 44.6° as a consequence of its bulky nature.
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0.15 and 0.18. However, compounds 5m and 5r display with
0.24 and 0.32 higher ΦF values. More information on the
dipolar nature of the exited state was obtained by a
solvatochromism study with the donor-substituted 1-methyl
Table 2. Glyoxylation−Alkynylation−Cyclocondensation Four-Component Synthesis of 2-Substituted 3-Ethynylquinoxalines 5
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Table 2. continued
a
b
All compounds were prepared on a 2.00 mmol scale except for compounds 5i, 5s, and 5v, which were prepared on a 1.00 mmol scale. Yields after
c
chromatography on silica gel. For the synthesis 5s, the glyoxylation step was carried out for 4 h at rt and the Stephens−Castro coupling was carried
out for 15 h at rt. Isomer ratio: 10:1, determined according to integrals in the H NMR spectrum. Isomer ratio: 6.5:1, determined according to
integrals in the H NMR spectrum.
d
e
1
1
Scheme 5. Consecutive Three-Component Synthesis of
3-Ethynylquinoxalines 7 through Activation−Alkynylation−
Cyclocondensation Sequence
While the UV/vis absorption spectra display only a minor
positive solvatochromism in the range from 405 to 415 nm, the
influence of the solvent polarity on the emission band is quite
̃
significant and positive, ranging from 468 to 525 nm, i.e., Δν =
2300 cm−1 (Figure 3). This pronounced positive emission
solvatochromism is additionally detectable upon eyesight,
where the emission color changes from blue (cyclohexane) to
orange (MeOH) (Figure 4).
The fluorescence quantum yield ΦF increases with decreasing
solvent polarity, and the highest quantum yields ΦF were
recorded in toluene (0.30). In protic solvents, such as alcohols,
even lower values than for acetonitrile (0.13) were observed.
indole derivative 5d in various solvents with solvent polarity
N
ET values ranging from 0.006 to 0.762 according to
Reichardt’s scale (Table 5).31
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Table 3. Activation−Alkynylation−Cyclocondensation Three-Component Synthesis of 2-Substituted 3-Ethynylquinoxalines 7
a
b
All compounds were prepared on a 2.00 mmol scale. Yields after chromatography on silica gel.
Figure 1. Solid-state pair building of compound 5d (left) and crystal packing of compound 5d (right).
Table 4. UV/vis Absorption and Emission Data of Selected 2-Substituted 3-Ethynylquinoxalines 5
a
b,
c
d
entry
absorption λmax,abs (nm) (ε (M−1cm−1))
emission λmax,em/nm (ΦF)
̃
Stokes shift Δν )
(cm−1
5a
5d
5h
5m
5r
273 (31600), 287 (30400), 319 (25200), 411 (9900)
271 (37300), 303 (33900), 323 (28400), 337 (sh), 408 (13300)
277 (sh), 290 (41600), 328 (27200), 418 (8000)
510 (0.16)
506 (0.19)
520 (0.15)
474 (0.24)
4700
4800
4700
4400
4800
266 (31300), 303 (31400), 337 (16300), 344 (sh), 393 (14600)
274 (21200), 312 (28400), 327 (sh), 343 (sh), 410 (11700)
508 (0.32)
a
b
c
Recorded in CH2Cl2, T = 293 K, c(5) = 10−5 M. Recorded in CH2Cl2, T = 293 K, c(5) = 10−7 M. Fluorescence quantum yields were recorded
d
̃
relative to coumarin 153 (ΦF = 0.45) as a standard in MeOH. Δν = 1/λmax,abs − 1/λmax,em.
A deactivation pathway from the excited state triggered by
intermolecular solvent/solute hydrogen bonding appears to be
a very likely explanation for this specific solvent effect.32
Furthermore, the Lippert−Mataga equation allows a more
quantitative treatment of the observed emission solvatochromism.33
Large positive emission solvatochromism correlates with a
considerable increase of the dipole moment on excitation.34
Hence, the solvent-dependent Stokes shifts were plotted against
the orientation polarizability Δf, which can be calculated
according to
The change in dipole moment from the ground to the
excited state can be calculated with the Lippert−Mataga
equation
2Δf
ν
̃
− ν
̃
=
(μE − μG)2 + const
a
f
hca3
where νa
̃
and νf
̃
represent the absorption and emission maxima
(in cm−1), μE and μG are the dipole moment in the excited and
ground state, h (6.6256 × 10−34 Js) is Planck’s constant, c
(2.9979 × 1010 cm/s) is the speed of light, and a is the radius of
the solvent cavity occupied by the molecule. Upon applying
the Lippert−Mataga equation on charge-transfer compounds,
typically, the Onsager radius is employed for a. This assump-
tion is reasonable in cases, where the dipole moment is
extended over a sticklike molecule.34 However, the com-
putations on compound 5d revealed that the charge trans-
fer only occurs between the indolyl substituent and the
n2 − 1
εr − 1
2εr + 1
Δf =
−
2n2 + 1
from the relative permittivity εr and the optical refractive index
n of the solvent. The linear correlation displays an excellent
goodness of fit (r2 = 0.92), which indicates a dominant
importance of a general solvent effect (Figure 5).34
F
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for the transition dipole moment Δμ. Nevertheless, with the
computed values for Δμ (gas phase: 9.47 D, using Turbomole
with the B3LYP functional and the def-TZVP basis set; CH2Cl2:
relaxed 6.48 D, nonrelaxed 6.91 D, using Gaussian 09 with CAM-
B3LYP functional and the 6-311G(d,p) basis set), we were able to
calculate the dipole radii in the gas phase (0.51 nm) and in
CH2Cl2 (relaxed 0.40 nm, nonrelaxed 0.42 nm). These results
nicely match our estimated dipole radius (Figure 6).
Electronic Structure. A deeper rationalization of the
observed photophysical behavior of the synthesized quinoxa-
lines 5 was sought by elucidating the electronic structure by
calculating UV/vis absorption spectra on the DFT level of
theory, with special focus on the origin of the four longest
wavelength absorption maxima of each structure. Therefore,
first the geometries of the ground-state structures were
optimized using Gaussian0935 with the B3LYP functional36
and the Pople 6-311G(d,p) basis set,37 and the starting
geometries obtained from X-ray structure analyses. Since all
measurements were recorded in solution, the calculations were
carried out using the polarizable continuum model (PCM)
applying dichloromethane as solvent.38 All minima structures
were confirmed by analytical frequency analyses.
Figure 2. UV/vis absorptiona (bold line) and emission spectrumb
(dashed line) of compound 5d. (aRecorded in CH2Cl2, T = 293 K,
b
c(5) = 10−5 M. Recorded in CH2Cl2, T = 293 K, c(5) = 10−7 M,
λexcit. = 420 nm.)
Table 5. Selected UV/vis Absorption and Emission Maxima
of Compound 5d, Measured in Solvents of Different Polarity
For the three different heteroaryl substituents in the 2-position
of the quinoxaline moiety, the computations nicely match the
equilibrium ground-state structures as obtained from X-ray
structure analyses. For compounds 5m and 5r, the torsional
angles between the quinoxaline plane and the heterocyclic ring in
2-position differ only slightly from the angles determined by X-ray
of 5n and 5q (vide supra and Figure 7). In contrast, calculations
suggest that the N-methylindole substituent of 5d is twisted
considerably more out of plane than it was found in the X-ray
(θcalc = 25° vs θX‑ray = 13°). Accordingly, the overlap and thereby
the electronic communication in the case of thienyl and indolyl
substituents is more efficient than that for the N-phenylpyrrole
substituent.
The frontier molecular orbitals of the quinoxalines 5d, 5m,
and 5r (Figure 8) show that for all three HOMOs the coefficient
density is predominantly located on the quinoxaline and on the
adjacent indolyl, pyrrolyl, and thienyl moiety, whereas the phenyl
core of the pyrrole 5m does not possess any coefficient den-
sity. For the quinoxaline derivatives 5m (Figure 8, center) and
emission λmax,em
/
absorption λ
/nm
Stokes shift
max,abs a
b,
c
d
solvent
Δν
̃
(cm−1
3200
)
nm (ΦF)
(ε (M−1cm−1))
407 (13300)
408 (13400)
405 (14400)
408 (13300)
408 (14000)
407 (13200)
415 (11700)
415 (12000)
415 (12300)
toluene
THF
468 (0.30)
490 (0.19)
491 (0.17)
506 (0.19)
513 (0.16)
518 (0.13)
519 (0.02)
4100
4320
4710
5000
5300
4800
4900
5100
EtOAc
CH2Cl2
acetone
MeCN
iPrOH
EtOH
522 (<0.01)
525 (<0.01)
MeOH
a
b
Recorded in CH2Cl2, T = 293 K, c(5) = 10−5 M. Recorded in
c
CH2Cl2, T = 293 K, c(5) = 10−7 M. Fluorescence quantum yields
were recorded relative to coumarin 153 (ΦF = 0.45) as a standard in
d
MeOH. Δν
̃
= 1/λmax,abs − 1/λmax,em
.
(4-methoxyphenyl)ethynyl moiety, whereas the quinoxaline
core, especially the benzo ring, is hardly involved. Therefore,
employing the Onsager radius would not lead to reliable values
Figure 3. UV/vis absorption (solid lines) and emission spectra (dashed lines) of compound 5d, measured in nine solvents of different polarity
(recorded at T = 293 K).
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Figure 4. Emission solvatochromism of compound 5d (recorded in cyclohexane, toluene, THF, EtOAc, acetone, CH2Cl2, MeCN, iPrOH, EtOH,
MeOH (from left to right); T = 293 K; c(5d) = 10−4 M; λexcit = 356 nm, hand-held UV lamp).
Figure 7. Optimized geometries at the B3LYP 6-311G(d,p) level for
the quinoxalines 5d, 5m, and 5r with different heteroaryl substituents
in 2-position.
Figure 5. Lippert plot for compound 5d (n = 9, r2 = 0.92).
Figure 8. HOMOs (bottom) and LUMOs (top) of the quinoxalines
5d, 5m, and 5r.
Figure 6. Estimation of the dipolar radius a of compound 5d.
5r (Figure 8, right) the coefficients are also large both on the
bridging triple bonds and the anisol cores, whereas only a
neglectible coefficient density can be observed on the anisyl
fragment of structure 5d. In all three cases, the LUMOs do not
bear any significant coefficient density on the heterocyclic
substituents in 2-position of the quinoxaline. Here, the coefficients
on the quinoxaline moieties are increased in comparison to the
HOMOs, whereas the LUMO coefficients on the bridged triple
bonds and the adjacent anisyl cores only show minor differences
for structure 5d (Figure 8, left) and a slightly diminished
coefficient density for the other two structures. Already the
computed ground-state structures indicate that HOMO−LUMO
transitions should be accompanied with a dominant charge-
transfer character from the heteroaryl substituents in 2-position to
the central quinoxaline core.
The optimized structures of 5a, 5d, 5h, 5m, and 5r were
submitted to TD-DFT calculations to study the absorption
characteristics (Table 6). The hybrid exchange-correlation
functional CAM-B3LYP39 was implemented and a non-
equilibrium solvation40 for the state-specific solvation of the
vertical excitation was included. Expectedly, the longest
wavelength absorption bands of all five computed molecules
result from dominant contributions of the HOMO−LUMO
transitions. The computed values are slightly hypsochromically
shifted in comparison to the experimental data. The absorption
maxima and shoulders appearing in the experimental UV/vis
spectra at lower wavelength ranges were identified by comparing
the oscillatory strength of the first 10 excitations of the first excited
state. The computed values are in reasonably good agreement
with the experimental data and major contributions of two more
absorption maxima at lower wavelengths emanate predominantly
from HOMO-1 → LUMO, HOMO-1 → LUMO+1, and
HOMO → LUMO+1 transitions. Only for structures 5h and 5r
are other molecular orbitals involved.
CONCLUSION
■
The improved glyoxylation−Stephens−Castro coupling−cyclo-
condensation protocol represents an efficient and rapid access
to 2-substituted 3-ethynylquinoxalines in the sense of a
consecutive MCR. As a consequence of its diversity-oriented
nature, large substance libraries are readily envisioned for
H
dx.doi.org/10.1021/jo4025978 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
(water/ice, 5 min). Then, oxalyl chloride (0.18 mL, 2.00 mmol, 1.0
equiv) was added dropwise to the reaction mixture. After being
warmed to room temperature (water bath, 5 min), the reaction
mixture was stirred for the indicated time at the indicated temperature
(water bath/oil bath). If necessary, the mixture was then cooled to
room temperature (water bath, 5 min). Then, CuI (20 mg, 0.1 mmol,
5 mol %), 1 equiv of phenylacetylene 2a (0.22 mL, 2.00 mmol, 1.0
equiv), and dry triethylamine (0.84 mL, 6.00 mmol, 3.0 equiv) were
successively added to the reaction mixture, and stirring at room
temperature was continued for the indicated time. 10 mL of water
was added, the phases were separated, and the aqueous phase was
extracted with dichloromethane (3 × 5 mL/10 mL, monitored by
TLC). The combined organic layers were dried with anhydrous
sodium sulfate. After removal of the solvents in vacuo, the residue was
absorbed onto Celite and purified chromatographically on silica gel
with petroleum ether (boiling range 40−60 °C)/ethyl acetate (ratio
Table 6. TD-DFT Calculations (CAM-B3LYP 6-311G(d,p))
of the UV/vis Absorption Maxima of the Quinoxalines 5a,
5d, 5h, 5m, and 5r
a
experimental λmax,abs
computed λmax,abs (nm)
(most dominant contributions)
structure
(nm)
5a
273
266 (HOMO-1 → LUMO+1)
298 (HOMO-1 → LUMO)
323 (HOMO → LUMO+1)
371 (HOMO → LUMO)
273 (HOMO-1 → LUMO+1)
299 (HOMO → LUMO+1)
330 (HOMO-1→ LUMO)
372 (HOMO → LUMO)
272 (HOMO-2 → LUMO+1)
308 (HOMO-2 → LUMO)
331 (HOMO → LUMO+1)
383 (HOMO → LUMO)
276 (HOMO-1 → LUMO+1)
290 (HOMO → LUMO+1)
327 (HOMO-1 → LUMO)
364 (HOMO → LUMO)
285 (HOMO-1 → LUMO+1)
305 (HOMO-1 → LUMO)
319 (HOMO-4 → LUMO)
343 (HOMO → LUMO+1)
373 (HOMO → LUMO)
287
319
411
5d
5h
5m
5r
271
303
323
408
277 (sh)
290
1
3:1) to give the ynedione 3a. Yellow solid. Mp: 128 °C. H NMR
(CDCl3, 300 MHz): δ 3.86 (s, 3 H), 7.36−7.53 (m, 6 H), 7.68−7.74
(m, 2 H), 8.33 (s, 1 H), 8.44−8.52 (m, 1 H). 13C NMR (CDCl3, 75
MHz): δ 33.8 (CH3), 87.7 (Cquat), 97.5 (Cquat), 105.1 (CH), 110.0
(CH), 110.8 (Cquat), 111.0 (CH), 119.7 (Cquat), 122.7 (CH), 123.6
(CH), 124.2 (CH), 127.2 (Cquat), 128.6 (CH), 131.2 (CH), 133.6
(CH), 137.2 (Cquat), 140.2 (CH), 178.6 (Cquat), 180.1 (Cquat). EI +
MS (m/z): 287 (M+, 2), 259 (C18H13NO+, 1), 231 (C17H13N+, 2), 158
328
418
266
303
337
393
([M − C9H5O]+, 100), 130 (C9H8N+, 7), 129 (C9H5O+), 103 (7), 97
274
+
3127 (w) [cm−1], 2914 (w),
312
(7), 77 (C6H5 , 6), 57 (13). IR (solid): ν
̃
327 (sh)
343 (sh)
410
2853 (w), 2200 (m), 2156 (w), 1734 (w), 1643 (m), 1624 (m), 1578
(m), 1526 (m), 1464 (m), 1443 (m), 1377 (m), 1335 (w), 1281 (m),
1225 (m), 1171 (w), 1130 (m), 1074 (m), 1032 (m), 977 (m), 880
(m), 772 (m), 754 (m), 739 (s), 685 (s), 621 (m). Anal. Calcd for
C19H13NO2 (287.3): C, 79.43; H, 4.56; N, 4.88. Found: C, 79.23; H,
4.76; N, 4.78.
a
Recorded in CH2Cl2, T = 293 K, c(5) = 10−5 M.
establishing experimentally founded structure−property rela-
tionships by variation of the individual components. Most
interestingly, the title compounds display substantial emission
solvatochromism and high quantum yields, as revealed by
detailed photophysical studies and computations to rationalize
the electronic structure. In addition, the ethynyl group is well
suited for incorporation of these solvatochromic lumophores
into more complex systems, most favorably as sensors for
protein interactions.26 Extended pluripotent functionalizations
of 2-substituted 3-ethynylquinoxalines as well as their intriguing
photophysics are currently under investigation.
General Procedure for the Four-Component Synthesis of
3-Ethynylchinoxalines 5. A 2.00 mmol portion of 1 in dry THF
(2.5 mL/mmol) was placed under argon or nitrogen atmosphere in a
sintered screw-cap Schlenk tube, degassed with argon or nitrogen, and
cooled to 0 °C (water/ice, 5 min) (for experimental details see Table 7).
Then, oxalyl chloride (0.18 mL, 2.00 mmol, 1.0 equiv) was added dropwise
to the reaction mixture at 0 °C. The mixture was first warmed to room
temperature (water bath, 5 min) and then stirred for 1 h at 50 °C
(oil bath). Thereafter, the mixture was cooled to room temperature (water
bath, 5 min). Then, CuI (20 mg, 0.1 mmol, 5 mol %), 1 equiv of terminal
alkyne 2, and dry triethylamine (0.84 mL, 6.00 mmol, 3.0 equiv) were
successively added to the reaction mixture, and stirring at room temp-
erature was continued for 6 h. Then, 2 mL of methanol, 2.00 mmol of the
1,2-diaminoarene 4 (1.0 equiv), and 2 mL of acetic acid were added
successively, the mixture was stirred at 50 °C for 1 h, 10 mL water was
added, the phases were separated, and the aqueous phase was extracted
with dichloromethane (3 × 5 mL/10 mL, monitored by TLC). The
combined organic layers were dried with anhydrous sodium sulfate. After
removal of the solvents in vacuo, the residue was absorbed onto Celite and
purified chromatographically on silica gel with petroleum ether (boiling
range 40−60 °C)/ethyl acetate to give the 3-ethinylchinoxalines 5.
2-(1-Methyl-1H-indol-3-yl)-3-(phenylethynyl)quinoxaline (5a).
Yellow solid (574 mg, 80%). Rf = 0.15 (petroleum ether/ethyl acetate
EXPERIMENTAL SECTION
■
General Considerations. Reagents, catalysts, ligands, and solvents
were purchased reagent grade and used without further purification.
Anhydrous tetrahydrofuran, 1,4-dioxane, dichloromethane, and 1,2-
dichloroethane were obtained from a drying system. Triethylamine
was refluxed under an argon atmosphere over sodium ketyl, distilled,
and stored in a Schlenk flask under nitrogen atmosphere over
potassium hydroxide pellets. Column chromatography: silica gel 60,
mesh 70−230. TLC: silica gel plates 60 F254. All products were purified
with column chromatography on silica gel 60 (0.040−0.063 mm)
using flash technique under a pressure of 2 bar. The crude mixtures
were absorbed on Celite 545 (0.02−0.10 mm) before chromato-
graphic 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 and with aqueous potassium
1
7:1). Mp: 134 °C. H NMR (CDCl3, 300 MHz): δ 3.82 (s, 3 H),
7.22−7.29 (m, 2 H), 7.30−7.36 (m, 4 H), 7.50−7.55 (m, 2 H), 7.58
(ddd, J = 8.1 Hz, J = 4.8 Hz, J = 1.4 Hz, 1 H), 7.99 (ddd, J = 8.3 Hz,
J = 6.9 Hz, J = 1.7 Hz, 1 H), 8.06 (dd, J = 8.2 Hz, J = 1.2 Hz, 1 H),
8.37 (s, 1 H), 8.64−8.71 (m, 1 H). 13C NMR (CDCl3, 75 MHz): δ
33.4 (CH3), 89.1 (Cquat), 94.1 (Cquat), 109.5 (CH), 112.4 (Cquat),
121.4 (CH), 122.0 (Cquat), 122.87 (CH), 122.93 (CH), 127.5 (Cquat),
128.59 (CH), 128.62 (CH), 128.7 (CH), 128.8 (CH), 129.5 (CH),
permanganate solution. Chemical shifts δ in the H NMR and 13C
1
NMR spectra are reported in ppm relative to CDCl3. The assignments
of quaternary C, CH, CH2, and CH3 signals were made by using
DEPT spectra.
General Procedure for the Three-Component Synthesis of
1-(1-Methyl-1H-indol-3-yl)-4-phenylbut-3-yne-1,2-dione (3a).
A 268 mg (2.00 mmol) portion of 1a was placed under argon or
nitrogen atmosphere in a screw-cap Schlenk tube with one of the listed
solvents. The solution was degassed with argon/nitrogen. In the cases
of THF, DCM, and DCE the solution was then cooled to 0 °C
130.4 (CH), 132.0 (CH), 132.5 (CH), 137.0 (Cquat), 137.3 (Cquat
)
137.4 (Cquat), 141.1 (Cquat), 151.6 (Cquat). EI + MS (m/z): 360 (17),
359 (74), 358 (M+, 100), 344 ([M − CH3]+, 9), 282 ([M − C6H5]+,
+
3), 180 (11), 172 (11), 158 (11), 156 (C10H8N2 , 8). IR (solid): ν
̃
3055 (w), 2955 (w), 2922 (w), 2853 (w), 2210 (w), 1535 (m), 1476
(w), 1454 (m), 1425 (w), 1406 (w), 1369 (m), 1352 (w), 1337 (w), 1300
(w), 1281 (w), 1256 (w), 1236 (w), 1215 (m), 1178 (w), 1157 (w),
I
dx.doi.org/10.1021/jo4025978 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
Table 7. Experimental Details for the Four-Component Synthesis of 2-Substituted 3-Ethynylquinoxalines 5
3-ethynyl-
quinoxaline 5 (yield, %)
a
b
entry
R1-H 1
alkyne 2
1,2-diaminoarene 4
1
268 mg (2.00 mmol) of 1a
268 mg (2.00 mmol) of 1a
268 mg (2.00 mmol) of 1a
268 mg (2.00 mmol) of 1a
268 mg (2.00 mmol) of 1a
268 mg (2.00 mmol) of 1a
268 mg (2.00 mmol) of 1a
268 mg (2.00 mmol) of 1a
134 mg (1.00 mmol) of 1a
164 mg (2.00 mmol) of 1b
289 mg (2.00 mmol) of 1c
289 mg (2.00 mmol) of 1c
289 mg (2.00 mmol) of 1c
289 mg (2.00 mmol) of 1c
446 mg (2.00 mmol) of 1d
470 mg (2.00 mmol) of 1e
470 mg (2.00 mmol) of 1e
470 mg (2.00 mmol) of 1e
128 mg (1.00 mmol) of 1f
268 mg (2.00 mmol) of 1a
268 mg (2.00 mmol) of 1a
134 mg (1.00 mmol) of 1a
268 mg (2.00 mmol) of 1a
268 mg (2.00 mmol) of 1a
0.18 mL (2.00 mmol) of 2a
0.28 mL (2.00 mmol) of 2b
0.45 mL (2.00 mmol) of 2c
267 mg (2.00 mmol) of 2d
0.36 mL (2.00 mmol) of 2e
0.38 mL (2.00 mmol) of 2f
320 mg (2.00 mmol) of (2g)
262 mg (2.00 mmol) of 2h
121 mg (1.00 mmol) of 2i
0.28 mL (2.00 mmol) of 2b
0.28 mL (2.00 mmol) of 2b
0.18 mL (2.00 mmol) of 2a
267 mg (2.00 mmol) of 2d
262 mg (2.00 mmol) of 2h
0.28 mL (2.00 mmol) of 2b
0.28 mL (2.00 mmol) of 2b
0.18 mL (2.00 mmol) of 2a
267 mg (2.00 mmol) of 2d
0.14 mL (1.00 mmol) of 2b
0.28 mL (2.00 mmol) of 2b
0.28 mL (2.00 mmol) of 2b
0.23 mL (1.00 mmol) of 2c
0.28 mL (2.00 mmol) of 2b
0.18 mL (2.00 mmol) of 2a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
108 mg (1.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
216 mg (2.00 mmol) of 4a
108 mg (1.00 mmol) of 4a
361 mg (2.00 mmol) of (4b)
313 mg (2.00 mmol) of 4c
107 mg (1.00 mmol) of 4d
326 mg (2.00 mmol) of 4e
326 mg (2.00 mmol) of 4e
574 mg (80%) of 5a
564 mg (79%) of 5b
749 mg (85%) of 5c
573 mg (74%) of 5d
455 mg (55%) of 5e
672 mg (81%) of 5f
709 mg (85%) of 5g
623 mg (81%) of 5h
265 mg (70%) of 5i
446 mg (73%) of 5j
552 mg (75%) of 5k
544 mg (73%) of 5l
589 mg (73%) of 5m
536 mg (68%) of 5n
496 mg (55%) of 5o
398 mg (59%) of 5p
192 mg (28%) of 5q
243 mg (33%) of 5r
437 mg (62%) of 5s
686 mg (81%) of 5t
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
c
19
20
21
22
23
24
d
694 mg (87%) of 5u
e
358 mg (72%) of 5v
537 mg (66%) of 5w
349 mg (43%) of 5x
a
b
All compounds were prepared on a 2.00 mmol scale except for compounds 5i, 5s, and 5v, which were prepared on a 1.00 mmol scale. Yields after
c
chromatography on silica gel. For the synthesis 5s, the glyoxylation step was carried out for 4 h at rt and the Stephens−Castro coupling was carried
out for 15 h at rt. Isomer ratio: 10:1, determined according to integrals in the H NMR spectrum. Isomer ratio: 6.5:1, determined according to
integrals in the H NMR spectrum.
d
e
1
1
1128 (m), 1111 (m), 1082 (m), 1011 (w), 937 (m), 905 (w), 839 (w),
827 (w), 740 (s), 681 (s), 656 (w), 640 (w), 611 (m). Anal. Calcd for
C25H17N3 (359.4): C, 83.59; H, 4.77; N, 11.69. Found: C, 83.50; H,
4.89; N, 11.40.
122.9 (CH), 123.0 (CH), 127.5 (Cquat), 128.5 (CH), 128.6 (CH),
128.7 (CH), 130.4 (CH), 132.6 (CH), 136.7 (Cquat), 137.3 (Cquat),
139.4 (Cquat), 141.0 (Cquat), 150.4 (Cquat). EI + MS (m/z): 440 (35),
439 (M+, 100), 397 (24), 396 ([M − C3H7]+, 70), 368 (11), 354 (26),
353 ([M − (C3H7)2]+, 6), 339 (11), 338 (10), 326 (20), 312 (12), 311
(21), 310 ([M − (C3H7)3]+, 33), 296 (13), 167 (12), 162 (12), 156
2-(1-Methyl-1H-indol-3-yl)-3-[(trimethylsilyl)ethynyl]quinoxaline
(5b). Yellow solid (564 mg, 79%). Rf = 0.32 (petroleum ether/ethyl
1
acetate 7:1). Mp: 160 °C. H NMR (CDCl3, 300 MHz): δ 0.37 (s, 9
̃
(12), 155 (11), 154 (10), 149 (17). IR (solid): ν 2945 (w), 2864 (w),
H), 3.91 (s, 3 H), 7.30−7.44 (m, 3 H), 7.65 (ddd, J = 8.3 Hz, J = 6.9
Hz, J = 1.4 Hz, 1 H), 7.73 (ddd, J = 8.3 Hz, J = 6.9 Hz, J = 1.5 Hz,
1 H), 8.04 (dd, J = 8.3 Hz, J = 1.5 Hz, 1 H), 8.12 (dd, J = 8.3 Hz, J =
1.5 Hz, 1 H), 8.58 (s, 1 H), 8.78−8.81 (m, 1 H). 13C NMR (CDCl3,
75 MHz): δ −0.5 (CH3), 33.3 (CH3), 100.9 (Cquat), 104.4 (Cquat),
109.4 (CH), 112.0 (Cquat), 121.5 (CH), 122.9 (CH), 123.1 (CH),
127.5 (Cquat), 128.57 (CH), 128.63 (CH), 128.7 (CH), 130.6 (CH),
132.8 (CH), 136.3 (Cquat), 137.2 (Cquat), 139.1 (Cquat), 141.1 (Cquat),
150.4 (Cquat). EI + MS (m/z): 356 (29), 355 (M+, 100), 354 (45), 341
(15), 340 ([M − CH3]+, 52), 325 ([M − (CH3)2]+, 7), 310 ([M −
(CH3)3]+, 10), 282 ([M − C3H9Si]+, 11), 156 (C10H8N2, 10), 157
1537 (m), 1526 (m), 1452 (m), 1423 (w), 1383 (m), 1371 (m), 1339
(w), 1310 (w), 1287 (w), 1242 (w), 1217 (m), 1200 (m), 1159 (w),
1142 (w), 1125 (w), 1084 (m), 1013 (w), 995 (w), 935 (m), 880 (m),
758 (m), 745 (s), 681 (s), 658 (m), 615 (m). Anal. Calcd for
C28H33N3Si (439.7): C, 76.49; H, 7.57; N, 9.56. Found: C, 76.68; H,
7.69; N, 9.42.
2-[(4-Methoxyphenyl)ethynyl]-3-(1-methyl-1H-indol-3-yl)-
quinoxaline (5d). Yellow solid (573 mg, 74%). Rf = 0.33
1
(dichloromethane). Mp: 164 °C. H NMR (CDCl3, 300 MHz): δ
3.77 (s, 3 H), 3.83 (s, 3 H), 6.79−6.93 (m, 2 H), 7.20−7.39 (m, 3 H),
7.41−7.51 (m, 2 H), 7.55−7.68 (m, 2 H), 7.99 (dd, J = 8.2 Hz, J = 1.4
Hz, 1 H), 8.05 (dd, J = 8.2 Hz, J = 1.2 Hz, 1 H), 8.38 (s, 1 H), 8.63−
8.71 (m, 1 H). 13C NMR (CDCl3, 75 MHz): δ 33.4 (CH3), 55.4
(CH3), 88.7 (Cquat), 94.9 (Cquat), 109.4 (CH), 112.4 (Cquat),
113.9 (Cquat), 114.3 (CH), 121.4 (CH), 123.0 (CH), 127.5 (Cquat),
128.4 (CH), 128.6 (CH), 128.8 (CH), 130.2 (CH), 132.6 (CH),
133.7 (CH), 137.4 (Cquat) 139.4 (Cquat), 140.8 (Cquat), 150.5 (Cquat),
160.7 (Cquat). EI + MS (m/z):. 390 (26), 389 (M+, 100), 388 (94), 374
([M − CH3]+, 21), 358 ([M-OCH3]+, 6), 346 (15), 345 (21), 282
̃
(18). IR (solid): ν 3065 (w), 2966 (w), 2160 (w), 1612 (w), 1531
(m), 1477 (w), 1454 (w), 1422 (w), 1369 (w), 1344 (w), 1337 (w),
1287 (m), 1248 (m), 1240 (m), 1215 (m), 1198 (w), 1161 (w), 1119
(m), 1082 (m), 1047 (w), 1013 (w), 935 (m), 914 (w), 841 (s), 758
(w), 727 (s), 700 (w), 646 (w), 633 (m), 615 (w). Anal. Calcd for
C22H21N3Si (355.5): C, 74.33; H, 5.95; N, 11.82. Found: C, 74.13; H,
5.76; N, 11.91.
2-(1-Methyl-1H-indol-3-yl)-3-[(triisopropylsilyl)ethynyl]-
quinoxaline (5c). Yellow solid (749 mg, 85%). Rf = 0.47 (petroleum
ether/ethyl acetate 6:1). Mp: 100 °C. 1H NMR (CDCl3, 300 MHz): δ
1.12−1.29 (m, 21 H), 3.88 (s, 3 H), 7.30−7.43 (m, 3 H), 7.64 (ddd,
J = 8.3 Hz, J = 6.9 Hz, J = 1.6 Hz, 1 H), 7.72 (ddd, J = 8.4 Hz, J = 6.9
Hz, J = 1.6 Hz, 1 H), 8.04 (dd, J = 8.3 Hz, J = 1.4 Hz, 1 H), 8.11 (dd,
J = 8.3 Hz, J = 1.4 Hz, 1 H), 8.59 (s, 1 H), 8.73−8.80 (m, 1 H). 13C
NMR (CDCl3, 75 MHz): δ 11.4 (CH), 18.7 (CH3), 33.2 (CH3),
97.6 (Cquat), 106.4 (Cquat), 109.4 (CH), 112.2 (Cquat), 121.4 (CH),
+
+
(C19H12N3 , 4), 232 (C16H12N2 , 4), 231 (13), 195 (11), 190 (11),
173 (14), 172 (16), 156 (11), 155 (11). IR (solid): ν 3044 (w), 2967
̃
(w), 2901 (w), 2197 (w), 1605 (w), 1539 (m), 1508 (m), 1454 (m),
1371 (w), 1292 (w), 1254 (m), 1236 (w), 1211 (w), 1167 (w), 1155
(w), 1125 (m), 1113 (m), 1082 (m), 1032 (m), 1011 (m), 937 (m),
822 (s), 795 (w), 756 (m), 741 (s), 625 (m). Anal. Calcd for
C26H19N3O (389.5): C, 80.18; H, 4.92; N, 10.79. Found: C, 80.00; H,
4.88; N, 10.68.
J
dx.doi.org/10.1021/jo4025978 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
2-[(4-Butylphenyl)ethynyl]-3-(1-methyl-1H-indol-3-yl)quinoxaline
(5e). Yellow solid (455 mg, 55%). Rf = 0.48 (dichloromethane). Mp:
129 °C. 1H NMR (CDCl3, 300 MHz): δ 0.95 (t, J = 7.3 Hz, 3 H), 1.38
(sext, J = 7.3 Hz, 2 H), 1.57−1.69 (m, 2 H), 2.65 (t, J = 7.7 Hz, 2 H),
3.91 (s, 3 H), 7.20−7.25 (m, 2 H), 7.30−7.44 (m, 3 H), 7.50−7.56
(m, 2 H), 7.66 (ddd, J = 8.4 Hz, J = 6.9 Hz, J = 1.6 Hz, 1 H), 7.73
(ddd, J = 8.3 Hz, J = 6.9 Hz, J = 1.7 Hz, 1 H), 8.03−8.11 (m, 1 H),
8.10−8.17 (m, 1 H), 8.48 (s, 1 H), 8.73−8.81 (m, 1 H). 13C NMR
(CDCl3, 75 MHz): δ 13.9 (CH3), 22.3 (CH2), 33.3 (CH2), 33.4
(CH3), 35.7 (CH2), 89.2 (Cquat), 94.7 (Cquat), 109.4 (CH), 112.3
(Cquat), 119.0 (Cquat), 121.4 (CH), 122.9 (CH), 127.5 (Cquat), 128.5
(CH), 128.6 (CH), 128.8 (CH), 130.3 (CH), 131.9 (CH), 132.6
(CH), 137.1 (Cquat), 137.3 (Cquat), 139.3 (Cquat), 140.9 (Cquat), 145.0
J = 1.1 Hz, 1 H), 8.25 (s, 1 H), 8.59−8.68 (m, 1 H). 13C NMR
(CDCl3, 75 MHz): δ 33.5 (CH3), 91.5 (Cquat), 93.1 (Cquat), 109.6
(CH), 112.4 (Cquat), 112.8 (Cquat), 118.1 (Cquat), 121.5 (CH), 122.6
(CH), 123.1 (CH), 126.7 (Cquat), 127.2 (Cquat), 128.7 (CH), 128.8
(CH), 129.2 (CH), 131.1 (CH), 132.1 (CH), 132.2 (CH), 132.4
(CH), 136.2 (Cquat), 137.3 (Cquat), 139.5 (Cquat), 141.3 (Cquat), 150.7
(Cquat). MALDI-MS: m/z = 385 [MH+]. IR (solid): ν
̃
3649 (w), 3123
(w), 3046 (w), 2907 (w), 2369 (w), 2224 (w), 1601 (w), 1541 (m),
1535 (m), 1499 (w), 1476 (w), 1456 (m), 1423 (w), 1404 (w), 1371
(m), 1352 (w), 1339 (w), 1300 (w), 1256 (w), 1236 (w), 1211 (m),
1130 (m), 1111 (m), 1082 (m), 1011 (w), 937 (m), 908 (w), 837 (w),
822 (w), 768 (s), 739 (s), 646 (w), 619 (w). Anal. Calcd for C26H16N4
(384.4): C, 81.23; H, 4.20; N, 14.57. Found: C, 81.28; H, 4.04; N,
14.33.
(Cquat), 150.6 (Cquat). MALDI-MS: m/z = 416.1 [MH+]. IR (solid): ν
̃
3100 (w), 3040 (w), 2959 (w), 2930 (w), 2899 (w), 2859 (w), 2311
(w), 2203 (w), 1528 (m), 1508 (m), 1474 (w), 1456 (w), 1423 (w),
1402 (w), 1368 (m), 1352 (w), 1339 (m), 1329 (w), 1296 (w), 1277
(w), 1256 (w), 1234 (w), 1211 (m), 1171 (w), 1153 (w), 1126 (m),
1113 (m), 1080 (m), 1047 (w), 1015 (m), 988 (w), 935 (m), 908 (w),
881 (w), 826 (m), 812 (w), 783 (w), 756 (s), 739 (s), 642 (w), 610
(m). Anal. Calcd for C29H25N3 (415.5): C, 83.82; H, 6.06; N, 10.11.
Found: C, 83.58; H, 6.28; N, 10.09.
2-[(4-Fluorophenyl)ethynyl]-3-(1-methyl-1H-indol-3-yl)-
quinoxaline (5i). Yellow solid (265 mg, 70%). Rf = 0.33 (dichloro-
methane). Mp: 176 °C. 1H NMR (CDCl3, 300 MHz): δ 3.88 (s, 3 H),
7.05−7.15 (m, 2 H), 7.29−7.45 (m, 3 H), 7.52−7.60 (m, 2 H), 7.68
(dd, J = 6.9 Hz, J = 1.5 Hz, 1 H), 7.73 (dd, J = 6.8 Hz, J = 1.5 Hz, 1
H), 8.06 (dd, J = 8.2 Hz, J = 1.3 Hz, 1 H), 8.13 (dd, J = 8.3 Hz, J = 1.1
Hz, 1 H), 8.36 (s, 1 H). 13C NMR (CDCl3, 75 MHz): δ 33.4 (CH3),
89.4 (Cquat), 92.9 (Cquat), 109.5 (CH), 112.4 (Cquat), 116.0 (d, J = 22.2
Hz, CH), 118.1 (d, J = 3.5 Hz, Cquat), 121.4 (CH), 122.8 (CH), 122.9
(CH), 127.4 (Cquat), 128.6 (CH), 128.7 (CH), 128.8 (CH), 130.5
(CH), 132.3 (CH), 134.0 (d, J = 8.6 Hz, CH), 136.9 (Cquat), 137.3
(Cquat), 139.4 (Cquat), 141.1 (Cquat), 150.6 (Cquat) 163.2 (d, J = 251.9
Hz, Cquat). EI + MS (m/z):. 377 (M+, 100), 376 (20), 159 (13), 158
2-[(4-tert-Butylphenyl)ethynyl]-3-(1-methyl-1H-indol-3-yl)-
quinoxaline (5f). Yellow solid (672 mg, 81%). Rf = 0.24 (petroleum
ether/ethyl acetate 8:1). Mp: 130 °C. 1H NMR (CDCl3, 300 MHz): δ
1.36 (s, 9 H), 3.92 (s, 3 H), 7.31−7.39 (m, 2 H), 7.40−7.47 (m, 3 H),
7.54−7.59 (m, 2 H), 7.67 (ddd, J = 8.2 Hz, J = 6.8 Hz, J = 1.6 Hz, 1
H), 7.73 (ddd, J = 8.2 Hz, J = 6.8 Hz, J = 1.7 Hz, 1 H), 8.07 (dd, J =
8.1 Hz, J = 1.3 Hz, 1 H), 8.14 (dd, J = 8.2 Hz, J = 1.2 Hz, 1 H), 8.49
(s, 1 H), 8.74−8.81 (m, 1 H). 13C NMR (CDCl3, 75 MHz): δ
31.1 (CH3), 33.5 (CH3), 35.0 (Cquat), 89.2 (Cquat), 94.6 (Cquat), 109.4
(CH), 112.4 (Cquat), 118.9 (Cquat), 121.4 (CH), 122.9 (CH),
125.7 (CH), 127.5 (Cquat), 128.5 (CH), 128.6 (CH), 128.7 (CH),
130.3 (CH), 131.8 (CH), 132.6 (CH), 137.2 (Cquat), 137.3 (Cquat),
139.3 (Cquat), 140.9 (Cquat), 150.6 (Cquat), 153.1 (Cquat). MALDI-MS:
̃
(100). IR (solid): ν 3044 (w), 2361 (w), 2201 (w), 1599 (w), 1533
(m), 1504 (m), 1476 (w), 1452 (w), 1404 (w), 1381 (w), 1356 (m),
1339 (w), 1298 (w), 1229 (m), 1213 (m), 1177 (w), 1150 (w), 1132
(w), 1111 (m), 1078 (w), 1013 (w), 935 (w), 822 (m), 797 (w), 748
(s), 621 (w), 619 (w). Anal. Calcd for C25H16FN3 (377.4): C, 79.56;
H, 4.27; N, 11.13. Found: C, 79.37; H, 4.40; N, 10.93.
2-(1-Methyl-1H-pyrrol-2-yl)-3-[(trimethylsilyl)ethynyl]quinoxaline
(5j). Brownish solid (446 mg, 73%). Rf = 0.88 (dichloromethane). Mp:
1
m/z = 416 [MH+]. IR (solid): ν
̃
3048 (w), 3030 (w), 2957 (w), 2930
53 °C. H NMR (CDCl3, 300 MHz): δ 0.31 (s, 9 H), 4.00 (s, 3 H),
6.24 (dd, J = 4.0 Hz, J = 2.6 Hz, 1 H), 6.84−6.87 (m, 1 H), 7.38 (dd,
J = 4.0 Hz, J = 1.7 Hz, 1 H), 7.62−7.68 (m, 1 H), 7.68−7.73 (m, 1 H),
7.94−7.97 (m, 1 H), 8.01−8.05 (m, 1 H). 13C NMR (CDCl3, 75
MHz): δ −0.6 (CH3), 37.1 (CH3), 101.6 (CH), 103.3 (Cquat), 107.4
(Cquat), 116.3 (CH), 128.1 (CH), 128.2 (Cquat), 128.5 (CH), 128.8
(CH), 129.2 (CH), 130.6 (CH), 137.2 (Cquat), 139.3 (Cquat), 140.1
(w), 2909 (w), 2866 (w), 2853 (w), 2376 (w), 2205 (w), 1533 (s),
1518 (m), 1506 (m), 1477 (w), 1452 (w), 1425 (w), 1371 (m), 1298
(w), 1236 (w), 1215 (m), 1130 (w), 1101 (m), 1082 (w), 1013 (w),
935 (m), 908 (w), 835 (w), 758 (m), 743 (s), 694 (w), 638 (w), 615
(m). Anal. Calcd for C29H25N3 (415.5): C, 83.82; H, 6.06; N, 10.11.
Found: C, 83.71; H, 5.95; N, 9.89.
(Cquat), 147.6 (Cquat). MALDI-MS: m/z = 306.4 [MH+]. IR (solid): ν
̃
2-[(4-Methoxycarbonylphenyl)ethynyl]-3-(1-methyl-1H-indol-3-
yl)quinoxaline (5g). Yellow solid (709 mg, 85%). Rf = 0.14
3067 (w), 2959 (w), 2845 (w), 2488 (w), 1541 (m), 1520 (w), 1489
(w), 1472 (w), 1450 (w), 1422 (m), 1400 (w), 1369 (w), 1337 (w),
1312 (w), 1277 (w), 1252 (w), 1227 (w), 1215 (w), 1184 (m), 1134
(w), 1123 (w), 1098 (w), 1065 (m), 980 (m), 959 (w), 912 (w), 878
(w), 843 (s), 810 (m), 760 (s), 739 (s), 692 (m), 658 (w), 631 (m),
606 (m). Anal. Calcd for C18H19N3Si (305.5): C, 70.78; H, 6.27; N,
13.76. Found: C, 70.89; H, 6.28; N, 13.77.
1
(dichloromethane). Mp: 182 °C. H NMR (CDCl3, 300 MHz): δ
3.88 (s, 3 H), 3.94 (s, 3 H), 7.30−7.39 (m, 2 H), 7.39−7.44 (m, 1 H),
7.58−7.64 (m, 2 H), 7.67 (ddd, J = 8.3 Hz, J = 6.9 Hz, J = 1.5 Hz, 1
H), 7.74 (ddd, J = 8.4 Hz, J = 6.9 Hz, J = 1.6 Hz, 1 H), 8.02−8.19 (m,
3 H), 8.11−8.16 (m, 1 H), 8.35 (s, 1 H), 8.67−8.75 (m, 1 H). 13C
NMR (CDCl3, 75 MHz): δ 33.4 (CH3), 52.3 (CH3), 92.0 (Cquat),
92.7 (Cquat), 109.5 (CH), 112.3 (Cquat), 121.4 (CH), 122.8 (CH),
123.0 (CH), 126.4 (Cquat), 127.3 (Cquat), 128.6 (CH), 128.7 (CH),
128.9 (CH), 129.7 (CH), 130.6 (Cquat), 130.7 (CH), 131.8 (CH),
132.3 (CH), 136.5 (Cquat), 137.3 (Cquat), 139.4 (Cquat), 141.2 (Cquat),
150.6 (Cquat), 166.2 (Cquat). MALDI-MS: m/z = 418 [MH+]. IR
2-(1-Phenyl-1H-pyrrol-3-yl)-3-[(trimethylsilyl)ethynyl]quinoxaline
(5k). Yellow resin (552 mg, 75%). Rf = 0.24 (petroleum ether/ethyl
acetate 20:1). 1H NMR (CDCl3, 300 MHz): δ 0.31 (s, 9 H), 6.44 (dd,
J = 3.8 Hz, J = 2.8 Hz, 1 H), 7.11 (dd, J = 2.7 Hz, J = 1.7 Hz, 1 H),
7.14−7.19 (m, 2 H), 7.21−7.28 (m, 3 H), 7.32 (dd, J = 3.8 Hz, J = 1.7
Hz, 1 H), 7.50−7.65 (m, 3 H), 7.96−8.02 (m, 1 H). 13C NMR
(CDCl3, 75 MHz): δ −0.5 (CH3), 101.8 (Cquat), 102.5 (Cquat), 109.3
(CH), 116.6 (CH), 125.4 (CH), 126.4 (CH), 127.0 (CH), 128.6
(CH), 128.66 (Cquat), 128.71 (CH), 129.6 (CH), 130.5 (CH), 137.6
(Cquat), 139.6 (Cquat), 140.0 (Cquat) 141.1 (Cquat), 147.5 (Cquat). EI +
MS (m/z): 368 (14), 367 (M+, 47), 366 (24), 353 (11), 337 ([M −
CH3]+, 38), 326 (10), 294 ([M − [Si(CH3)3]+, 5), 290 ([M −
(C5H6)], 12), 243 (13), 149 (17), 101 (11), 59 (23), 58 (11); 57 (17),
̃
(solid): ν 3649 (w), 3127 (w), 3046 (w), 3019 (w), 2992 (w), 2945
(w), 2913 (w), 2874 (w), 2835 (w), 2313 (w), 2205 (w), 1719 (s),
1603 (w), 1539 (m), 1506 (w), 1474 (w), 1454 (w), 1429 (w), 1402
(w), 1369 (w), 1339 (w), 1271 (m), 1236 (m), 1217 (m), 1171 (m),
1132 (m), 1101 (m), 1082 (m), 1049 (w), 1015 (m), 935 (m), 907
(w), 847 (w), 816 (w), 748 (s), 687 (m), 646 (w), 615 (m). Anal.
Calcd for C27H19N3O2 (417.5): C, 77.68; H, 4.59; N, 10.07. Found: C,
77.54; H, 4.70; N, 9.90.
̃
56 (19), 55 (13), 43 (100), 41 (18). IR (solid): ν 2957 (w), 1597 (w),
2-[(4-Cyanophenyl)ethynyl]-3-(1-methyl-1H-indol-3-yl)-
quinoxaline (5h). Yellow solid (623 mg, 81%). Rf = 0.12
1541 (w), 1520 (w), 1499 (m), 1470 (w), 1456 (w), 1425 (m), 1391
(w), 1354 (w), 1327 (w), 1306 (w), 1281 (w), 1250 (w), 1229 (w),
1207 (m), 1182 (w), 1132 (m), 1123 (m), 1074 (w), 947 (m), 910
(w), 885 (w), 841 (s), 810 (m), 797 (w), 758 (s), 725 (s), 696 (s),
663 (m), 631 (m), 613 (m). Anal. Calcd for C23H21N3Si (367.5): C,
75.17; H, 5.76; N, 11.43. Found: C, 75.10; H, 5.81; N, 11.32.
1
(dichloromethane). Mp: 245 °C. H NMR (CDCl3, 300 MHz): δ
3.91 (s, 3 H), 7.35 (tdd, J = 8.4 Hz, J = 7.0 Hz, J = 1.6 Hz, 2 H), 7.41−
7.46 (m, 1 H), 7.60 (m 2 H), 7.67 (m, 2 H), 7.70 (ddd, J = 8.5 Hz, J =
6.9 Hz, J = 1.6 Hz, 1 H), 7.78 (ddd, J = 8.4 Hz, J = 7.0 Hz, J = 1.6 Hz,
1 H), 8.07 (dd, J = 8.2 Hz, J = 1.2 Hz, 1 H), 8.15 (dd, J = 8.2 Hz,
K
dx.doi.org/10.1021/jo4025978 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
2-(1-Phenyl-1H-pyrrol-2-yl)-3-(phenylethynyl)quinoxaline (5l).
Yellow solid (544 mg, 73%). Rf = 0.53 (dichloromethane). Mp:
109 °C. 1H NMR (CDCl3, 300 MHz): δ 6.51 (dd, J = 3.8 Hz, J = 2.8
Hz, 1 H), 7.12−7.19 (m, 3 H), 7.19−7.25 (m, 2 H), 7.30 (dd, J = 3.8
Hz, J = 1.7 Hz, 1 H), 7.37−7.44 (m, 3 H), 7.57−7.64 (m, 4 H), 7.65−
7.70 (m, 1 H), 7.99−8.05 (m, 1 H). 13C NMR (CDCl3, 75 MHz): δ
88.0 (Cquat), 94.9 (Cquat), 109.6 (CH), 116.2 (CH), 121.8 (Cquat),
125.2 (CH), 126.4 (CH), 126.6 (CH), 128.45 (CH), 128.52 (CH),
128.78 (CH), 128.81 (CH), 129.1 (Cquat), 129.5 (CH), 129.7 (CH),
130.4 (CH), 132.3 (CH), 138.3 (Cquat), 139.9 (Cquat), 140.1 (Cquat),
140.9 (Cquat), 148.0 (Cquat). MALDI-MS: m/z = 372 [MH+]. IR
797 (m), 768 (s), 727 (m), 691 (s), 662 (s), 650 (m), 633 (m),
631 (m). Anal. Calcd for C26H37N3Si2 (447.8): C, 69.74; H, 8.33; N,
9.38. Found: C, 69.50; H, 8.24; N, 9.11.
2-(5-Methoxythiophene-2-yl)-3-[(trimethylsilyl)ethynyl]-
quinoxaline (5p). Yellow solid (398 mg, 59%). Rf = 0.24 (petroleum
ether/ethyl acetate 20:1). Mp: 148 °C. 1H NMR (CDCl3, 300 MHz):
δ 0.37 (s, 9 H), 3.99 (s, 3 H), 6.28 (d, J = 4.3 Hz, 1 H), 7.62 (ddd, J =
8.2 Hz, J = 6.9 Hz, J = 1.6 Hz, 1 H), 7.68 (ddd, J = 8.3 Hz, J = 6.9 Hz,
J = 1.7 Hz, 1 H), 7.94 (ddd, J = 8.3 Hz, J = 1.7 Hz, J = 0.7 Hz, 1 H),
7.99 (ddd, J = 8.3 Hz, J = 1.7 Hz, J = 0.7 Hz, 1 H), 8.35 (d, J = 4.3 Hz,
1 H). 13C NMR (CDCl3, 75 MHz): δ −0.6 (CH3), 60.1 (CH3), 102.2
(Cquat),103.4 (Cquat), 105.2 (CH), 128.1 (Cquat), 128.3 (CH), 128.6
(CH), 129.1 (CH), 129.9 (CH), 130.9 (CH), 134.1 (Cquat), 139.7
(Cquat), 140.6 (Cquat) 147.5 (Cquat), 171.3 (Cquat). EI + MS (m/z): 340
(11), 339 (26), 338 (M+, 100), 323 ([M − CH3]+, 9), 308 ([M −
(CH3)2], 6), 307 ([M-OCH3], 4), 295 (11), 293 ([M − (CH3)3]+, 4),
280 (13), 279 (10), 265 ([M-Si(CH3)3]+, 7), 205 (21), 140 (11), 43
̃
(solid): ν 3647 (w), 3057 (w), 2360 (w), 2330 (w), 2210 (w), 1989
(w), 1965 (w), 1597 (w), 1541 (m), 1491 (m), 1470 (w), 1431 (m),
1393 (w), 1360 (m), 1325 (w), 1306 (w), 1288 (w), 1252 (w), 1206
(w), 1153 (w), 1115 (m), 1105 (w), 1049 (m), 1007 (w), 945 (m),
914 (w), 870 (w), 760 (s), 727 (s), 700 (m), 687 (s), 667 (m), 650
(w), 627 (w). Anal. Calcd for C26H17N3 (371.4): C, 84.07; H, 4.61; N,
11.31. Found: C, 83.90; H, 4.76; N, 11.39.
̃
(25). IR (solid): ν 2953 (w), 2897 (w), 2154 (w), 1551 (w), 1479 (s),
1452 (m), 1418 (s), 1395 (m), 1358 (w), 1339 (m), 1310 (w), 1250
(m), 1215 (s), 1180 (m), 1134 (m), 1125 (w), 1067 (s), 986 (m), 939
(w), 845 (s), 810 (w), 750 (s), 737 (m), 725 (w), 702 (w), 640 (w),
625 (w). Anal. Calcd for C18H18N2OSSi (338.5): C, 63.87; H, 5.36; N,
8.28. Found: C, 63.64; H, 5.64; N, 8.00.
2-[(4-Methoxyphenyl)ethynyl]-3-(1-phenyl-1H-pyrrol-2-yl)-
quinoxaline (5m). Greenish solid (589 mg, 73%). Rf = 0.39
1
(dichloromethane). Mp: 137 °C. H NMR (CDCl3, 300 MHz): δ
3.85 (s, 3 H), 6.50 (dd, J = 3.7 Hz, J = 2.8 Hz, 1 H), 6.88−6.96 (m, 2
H), 7.12−7.19 (m, 3 H), 7.19−7.25 (m, 3 H), 7.28 (dd, J = 3.8 Hz, J =
1.7 Hz, 1 H), 7.51−7.57 (m, 2 H), 7.57−7.68 (m, 3 H), 7.98−8.04 (m,
1 H). 13C NMR (CDCl3, 75 MHz): δ 55.3 (CH3), 87.3 (Cquat), 95.6
(Cquat), 109.5 (CH), 113.9 (Cquat), 114.2 (CH), 116.1 (CH), 125.2
(CH), 126.4 (CH), 126.5 (CH), 128.4 (CH), 128.76 (CH), 128.79
(CH), 129.2 (Cquat), 129.7 (CH), 130.1 (CH), 134.0 (CH), 138.7
(Cquat), 139.90 (Cquat), 139.93 (Cquat), 140.9 (Cquat), 147.9 (Cquat),
2-(5-Methoxythiophene-2-yl)-3-(phenylethynyl)quinoxaline (5q).
Yellow crystals (192 mg, 28%). Rf = 0.16 (petroleum ether/ethyl
acetate 10:1). Mp: 164 °C. 1H NMR (CDCl3, 300 MHz): δ 3.99 (s, 3
H), 6.31 (d, J = 4.3 Hz, 1 H), 7.40−7.47 (m, 3 H), 7.60−7.73 (m, 4
H), 7.91−7.98 (m, 1 H), 8.01 (dd, J = 8.1 Hz, J = 1.3 Hz, 1 H), 8.31
(d, J = 4.3 Hz, 1 H). 13C NMR (CDCl3, 75 MHz): δ 60.1 (CH3), 88.6
(Cquat), 94.9 (Cquat), 105.5 (CH), 121.7 (Cquat), 128.2 (Cquat), 128.4
(CH), 128.55 (CH), 128.59 (CH), 129.1 (CH), 129.5 (CH),
129.7 (CH), 130.8 (CH), 132.1 (CH), 134.7 (Cquat), 139.9 (Cquat),
140.6 (Cquat), 147.5 (Cquat), 171.2 (Cquat). EI + MS (m/z): 343 (24),
342 (M+, 100), 328 (10), 327 ([M − CH3]+, 46), 300 (17), 299 (72),
298 (30), 267 (13), 156 (17), 155 (11), 149 (16), 128 (21), 127 (21).
160.6 (Cquat). MALDI-MS: m/z = 402 [MH+]. IR (solid): ν
̃
3672 (w),
3055 (w), 2988 (m), 2972 (m), 2937 (m), 2901 (m), 2540 (w), 2351
(w), 2208 (w), 1599 (m), 1543 (m), 1497 (m), 1468 (m), 1429 (m),
1416 (m), 1393 (m), 1360 (m), 1287 (m), 1248 (m), 1206 (m), 1153
(m), 1115 (m), 1101 (m), 1057 (s), 1042 (s), 1028 (s), 1003 (m), 947
(m), 937 (w), 870 (w), 827 (s), 760 (s), 743 (m), 727 (s), 698 (s),
662 (m), 625 (m). Anal. Calcd for C27H19N3O (401.5): C, 80.78; H,
4.77; N, 10.47. Found: C, 80.57; H, 4.60; N, 10.50.
̃
IR (solid): ν 3065 (w), 2933 (w), 2210 (w), 1543 (w), 1477 (s), 1452
(w), 1416 (s), 1396 (m), 1285 (w), 1258 (w), 1209 (m), 1150 (w),
1132 (m), 1111 (m), 1059 (m), 1024 (w), 995 (m), 953 (w), 934
(m), 908 (w), 874 (w), 847 (w), 824 (w), 777 (m), 760 (m), 754 (s),
737 (m), 723 (m), 690 (s), 664 (m), 622 (m), 611 (m). Anal. Calcd
for C21H14N2OS (342.4): C, 73.66; H, 4.12; N, 8.18, S 9.36. Found: C,
73.89; H, 4.18; N, 8.10, S 9.32.
2-[(4-Cyanophenyl)ethynyl]-3-(1-phenyl-1H-pyrrol-2-yl)-
quinoxaline (5n). The compound was obtained as a yellow solid (536
mg, 68%). Rf = 0.12 (dichloromethane). Mp: 214 °C. 1H NMR
(CDCl3, 300 MHz): δ 6.50 (dd, J = 3.8 Hz, J = 2.8 Hz, 1 H), 7.11−
7.18 (m, 3 H), 7.20−7.28 (m, 4 H), 7.63−7.72 (m, 7 H), 7.99−8.04
(m, 1 H). 13C NMR (CDCl3, 75 MHz): δ 91.6 (Cquat), 92.0 (Cquat),
109.7 (CH), 112.7 (Cquat), 116.1 (CH), 118.2 (Cquat), 125.1 (CH),
126.56 (CH), 126.63 (Cquat), 126.8 (CH), 128.6 (CH), 128.8 (Cquat),
128.85 (CH), 128.88 (CH), 130.0 (CH), 131.0 (CH), 132.1 (CH),
132.6 (CH), 137.3 (Cquat), 139.9 (Cquat), 140.3 (Cquat), 140.8 (Cquat),
2-[(4-Methoxyphenyl)ethynyl]-3-(5-methoxythiophene-2-yl)-
quinoxaline (5r). Yellow crystals (243 mg, 33%). Rf = 0.15 (petroleum
ether/ethyl acetate 5:1). Mp: 120 °C. 1H NMR (CDCl3, 300 MHz): δ
3.85 (s, 3 H), 3.99 (s, 3 H), 6.31 (d, J = 4.3 Hz, 1 H), 6.94 (d, J = 8.6
Hz, 2 H), 7.56−7.75 (m, 4 H), 7.87−8.08 (m, 2 H), 8.32 (dd, J = 4.3
Hz, 1 H). 13C NMR (CDCl3, 75 MHz): δ 55.4 (CH3), 60.1 (CH3),
87.8 (Cquat), 95.5 (Cquat), 105.4 (CH), 113.7 (Cquat), 114.3 (CH),
128.26 (Cquat), 128.33 (CH), 128.5 (CH), 129.1 (CH), 129.5 (CH),
130.5 (CH), 133.7 (CH), 135.0 (Cquat), 140.0 (Cquat), 140.4 (Cquat),
147.5 (Cquat), 160.76 (Cquat), 171.1 (Cquat). EI + MS (m/z): 373 (24),
372 (M+, 100), 357 ([M − CH3]+, 12), 342 ([M − (CH3)2]+, 9), 330
(17), 329 (76), 314 (39), 298 (15), 286 (34), 285 (17), 165 (25), 157
147.9 (Cquat). MALDI-MS: m/z = 397.3 [MH+]. IR (solid): ν
̃
3057
(w), 2222 (w), 1595 (w), 1543 (w), 1520 (w), 1495 (m), 1472 (w),
1429 (m), 1395 (w), 1358 (m), 1323 (w), 1277 (w), 1252 (w), 1221
(w), 1198 (w), 1171 (w), 1153 (w), 1115 (m), 1096 (m), 1074 (w),
1047 (m), 1036 (w), 1013 (w), 945 (m), 908 (w), 870 (w), 827 (m),
795 (w), 760 (s), 725 (s), 689 (m), 664 (m). Anal. Calcd for
C27H16N4 (396.4): C, 81.80; H, 4.07; N, 14.13. Found: C, 81.57; H,
4.08; N, 14.05.
(C10H7NO+, 10), 149 (10), 143.4 (15), 142.6 (29). IR (solid): ν
̃
3059
(w), 3046 (w), 2933 (w), 2830 (w), 2207 (m), 1603 (m), 1551 (w),
1510 (m), 1489 (s), 1474 (m), 1454 (m), 1423 (m), 1398 (m), 1352
(m), 1292 (m), 1246 (s), 1204 (s), 1182 (m), 1132 (m), 1113 (m),
1061 (s), 1034 (s), 995 (m), 935 (m), 910 (w), 841 (m), 808 (m),
779 (s), 758 (s), 723 (m), 646 (w), 608 (m). Anal. Calcd for
C22H16N2O2S (372.4): C, 70.95; H, 4.33; N, 7.52. Found: C, 70.69; H,
4.47; N, 7.31.
2-[1-(Triisopropylsilyl)-1H-pyrrol-3-yl]-3-[(trimethylsilyl)ethynyl]-
quinoxaline (5o). Yellow solid (496 mg, 55%. Rf = 0.26 (petroleum
ether/ethyl acetate 20:1. Mp: 119 °C. 1H NMR (CDCl3, 300 MHz): δ
0.34 (s, 9 H), 1.16 (d, J = 7.5 Hz, 18 H), 1.54 (sept, J = 7.5 Hz, 3 H),
6.86 (dd, J = 2.8 Hz, J = 2.1 Hz, 1 H), 7.37 (dd, J = 2.9 Hz, J = 1.4 Hz,
1 H), 7.60 (ddd, J = 8.3 Hz, J = 6.9 Hz, J = 1.5 Hz, 1 H), 7.67 (ddd, J =
8.3 Hz, J = 6.9 Hz, J = 1.7 Hz, 1 H), 7.96−8.04 (m, 3 H). 13C NMR
(CDCl3, 75 MHz): δ −0.4 (CH3), 11.7 (CH), 17.8 (CH3), 100.5
(Cquat), 104.3 (Cquat), 112.0 (CH), 124.3 (Cquat), 124.9 (CH), 127.5
(CH), 128.5 (CH), 128.59 (CH), 128.62 (CH), 130.4 (CH), 136.0
(Cquat), 139.8 (Cquat), 141.2 (Cquat), 149.7 (Cquat). MALDI-MS: m/z =
2-(Azulen-1-yl)-3-[(trimethylsilyl)ethynyl]quinoxaline (5s). Dark
green solid (437 mg, 62%). Rf = 0.28 (petroleum ether/ethyl acetate
1
10:1). Mp: 105 °C. H NMR (CDCl3, 300 MHz): δ 0.19 (s, 9 H),
7.30−7.43 (m, 2 H), 7.46 (d, J = 4.1 Hz, 1 H), 7.64−7.83 (m, 3 H),
8.10−8.15 (m, 2 H), 8.46 (d, J = 9.5 Hz, 1 H), 8.75 (d, J = 4.1 Hz, 1
H), 9.15 (d, J = 9.7 Hz, 1 H). 13C NMR (CDCl3, 75 MHz): δ −0.7
(CH3), 101.6 (Cquat), 103.5 (Cquat), 117.1 (CH), 124.3 (Cquat), 125.1
(CH), 125.9 (CH), 128.78 (CH), 128.83 (CH), 129.4 (CH),
448 [MH+]. IR (solid): ν
̃
2945 (w), 2924 (w), 2866 (w), 2361 (w),
1539 (m), 1522 (w), 1493 (m), 1456 (w), 1319 (w), 1248 (m), 1227
(w), 1202 (m), 1128 (m), 1105 (s), 1086 (w), 1072 (w), 1034 (w),
1016 (w), 995 (w), 959 (w), 934 (w), 883 (m), 843 (s), 816 (m),
L
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130.7 (CH), 137.1 (CH), 137.5 (CH), 138.5 (Cquat), 138.6 (CH),
139.1 (Cquat), 139.4 (CH), 139.8 (Cquat) 140.8 (Cquat) 143.4 (Cquat),
152.3 (Cquat). EI + MS (m/z): 353 (29), 352 (M+, 100), 351 (82), 337
([M − CH3]+, 15), 307 ([M − (CH3)2]+, 9), 293 (16), 280 (10), 279
([M-Si(CH3)3]+, 26), 228 (26), 227 (10), 153 (C11H7N, 18). IR
1533 (s), 1522 (s), 1480 (w), 1464 (m), 1452 (m), 1435 (m), 1373
(s), 1339 (w), 1304 (w), 1279 (m), 1240 (s), 1207 (m), 1186 (w),
1159 (m), 1142 (w), 1117 (m), 1086 (m), 1015 (w), 997 (w), 935
(m), 883 (m), 839 (m), 824 (w), 791 (w), 761 (s), 741 (s), 681 (s),
654 (s), 611 (s). Anal. Calcd for C27H32N4Si (440.6): C, 73.59; H,
7.32; N, 12.71. Found: C, 73.74; H, 7.28; N, 12.54.
̃
(solid): ν 3053 (w), 2958 (w), 1524 (w), 1504 (w), 1472 (w), 1422
2-(1-Methyl-1H-indol-3-yl)-3-[(trimethylsilyl)ethynyl]benzo[g]-
(w), 1396 (m), 1310 (w), 1296 (w), 1250 (w), 1207 (m), 1190 (w),
1136 (w), 1123 (w), 1088 (w), 1051 (w), 1003 (w), 957 (w), 924 (w),
912 (w), 872 (w), 843 (s), 800 (w), 781 (s), 758 (s), 733 (m), 706
(w), 631 (w), 613 (m). Anal. Calcd for C23H20N2Si (352.5): C, 78.37;
H, 5.72; N, 7.95. Found: C, 78.28; H, 5.48; N, 7.94.
quinoxaline (5w). Orange solid (537 mg, 66%). Rf = 0.65
1
(dichloromethane). Mp: 251 °C. H NMR (CDCl3, 300 MHz): δ
0.39 (s, 9 H), 3.92 (s, 3 H), 7.35−7.45 (m, 3 H), 7.48−7.58 (m, 2 H),
8.02−8.12 (m, 2 H), 8.59 (s, 1 H), 8.64 (s, 2 H), 8.87−8.95 (m, 1 H).
13C NMR (CDCl3, 75 MHz): δ −0.5 (CH3), 33.4 (CH3), 101.4
(Cquat), 104.7 (Cquat), 109.4 (CH), 112.3 (Cquat), 121.6 (CH), 123.1
(CH), 123.3 (CH), 126.16 (CH), 126.19 (CH), 127.0 (CH), 127.1
(CH), 127.6 (Cquat), 128.3 (CH), 128.8 (CH), 133.2 (Cquat), 133.3
(CH), 134.6 (Cquat), 136.2 (Cquat), 137.3 (Cquat), 137.6 (Cquat), 137.7
6,7-Dichloro-2-(1-methyl-1H-indol-3-yl)-3-[(trimethylsilyl)-
ethynyl]quinoxaline (5t). Yellow solid (686 mg, 81%). Rf = 0.90
(dichloromethane). Mp: 237 °C. 1H NMR (CDCl3, 300 MHz): δ 0.39
(s, 9 H), 3.89 (s, 3 H), 7.30−7.41 (m, 3 H), 8.07 (d, J = 0.4 Hz, 1 H),
8.15 (d, J = 0.4 Hz, 1 H), 8.63 (s, 1 H), 8.71−8.77 (m, 1 H). 13C NMR
(CDCl3, 75 MHz): δ −0.5 (CH3), 33.4 (CH3), 102.3 (Cquat), 104.0
(Cquat), 109.5 (CH), 111.6 (Cquat), 121.8 (CH), 123.2 (CH), 123.2
(CH), 127.3 (Cquat), 129.0 (CH), 130.9 (CH), 132.6 (Cquat), 133.4
(CH), 134.8 (Cquat), 136.9 (Cquat), 137.2 (Cquat), 137.5 (Cquat), 139.8
(Cquat), 149.8 (Cquat). MALDI-MS: m/z = 406 [MH+]. IR (solid): ν
̃
3046 (w), 2951 (w), 2891 (w), 1528 (s), 1474 (w), 1464 (w), 1447 (w),
1420 (w), 1369 (m), 1339 (w), 1296 (w), 1260 (w), 1248 (m), 1229
(m), 1215 (w), 1177 (w), 1159 (w), 1130 (w), 1088 (m), 1053 (w), 1016
(w), 937 (w), 870 (m), 843 (s), 793 (w), 770 (w), 748 (s), 737 (s), 702
(w), 691 (w), 642 (w), 627 (m), 605 (w). Anal. Calcd for C26H23N3Si
(405.6): C, 77.00; H, 5.72; N, 10.36. Found: C, 76.78; H, 5.87; N, 10.32.
2-(1-Methyl-1H-indol-3-yl)-3-(phenylethynyl)benzo[g]-
quinoxaline (5x). Orange solid (349 mg, 43%). Rf = 0.87
(Cquat), 151.1 (Cquat). MALDI-MS: m/z = 424.0 [MH+]. IR (solid): ν
̃
3138 (w), 2957 (w), 2928 (w), 2895 (w), 1946 (w), 1867 (w), 1587
(w), 1516 (m), 1462 (w), 1443 (m), 1406 (w), 1400 (w), 1362 (m),
1337 (w), 1312 (w), 1285 (w), 1246 (m), 1238 (m), 1225 (w), 1198
(m), 1179 (m), 1157 (m), 1126 (w), 1099 (m), 1084 (m), 1051 (w),
1018 (w), 974 (w), 935 (m), 880 (m), 860 (m), 835 (s), 797 (w), 745
(s), 727 (m), 702 (m), 664 (m), 644 (m), 623 (m). Anal. Calcd for
C22H19Cl2N3Si (424.4): C, 62.26; H, 4.51; N, 9.90. Found: C, 62.12;
H, 4.35; N, 9.79.
1
(dichloromethane). Mp: 249 °C. H NMR (CDCl3, 300 MHz): δ
3.92 (s, 3 H), 7.36−7.49 (m, 6 H), 7.50−7.59 (m, 2 H), 7.63−7.66
(m, 2 H), 8.08 (d, J = 9.6 Hz, 2 H) 8.53 (s, 1 H), 8.61 (s, 1 H), 8.67 (s,
1 H), 8.85−8.91 (m, 1 H). 13C NMR (CDCl3, 75 MHz): δ 33.5
(CH3), 90.1 (Cquat), 94.5 (Cquat), 109.5 (CH), 112.6 (Cquat), 121.6
(CH), 121.9 (Cquat), 123.1 (CH), 123.2 (CH), 126.2 (CH),
126.3 (CH), 126.9 (CH), 127.0 (CH), 127.6 (Cquat), 128.3 (CH),
128.68 (CH), 128.73 (CH), 129.7 (CH), 132.0 (CH), 133.0 (CH),
133.3 (Cquat), 134.6 (Cquat), 136.5 (Cquat), 137.4 (Cquat) 137.6 (Cquat),
138.3 (Cquat), 150.1 (Cquat). EI + MS (m/z): 410 (23), 409 (M+, 88), 408
(100), 394 ([M − CH3]+, 11), 332 ([M − Ph]+, 3), 282 (C20H14N2+, 5),
281 (12), 204.4 (20), 203.5 (18), 197 (13), 156 (17), 155 (12), 126 (24).
2-(1-Methyl-1H-indol-3-yl)-6-nitro-3-[(trimethylsilyl)ethynyl]-
quinoxalines and 2-(1-Methyl-1H-indol-3-yl)-7-nitro-3-
[(trimethylsilyl)ethynyl]quinoxaline (5u). Red solid (694 mg, 87%).
1
Rf = 0.58 (dichloromethane). Mp: 232 °C. H NMR (CDCl3, 300
MHz): isomer ratio =10:1; δ 0.41 (s, 9 H), 3.92 (s, 3 H), 7.34−7.45
(m, 3 H), 8.08 (dd, J = 9.1 Hz, J = 0.5 Hz, 1 H), 8.34 (dd, J = 9.1 Hz,
J = 2.5 Hz, 1 H), 8.71 (s, 1 H), 8.78−8.86 (m, 1 H), 8.91 (dd, J = 2.5
Hz, J = 0.5 Hz, 1 H); additional signals for the minor isomer: δ 8.12
(dd, J = 9.2 Hz, J = 0.5 Hz, 1 H), 8.43 (dd, J = 9.2 Hz, J = 2.5 Hz, 1
H). 13C NMR (CDCl3, 75 MHz): δ −0.6 (CH3), 33.5 (CH3), 103.91
(Cquat), 103.94 (Cquat), 109.6 (CH), 111.4 (Cquat), 121.7 (CH), 122.1
(CH), 123.3 (CH), 123.5 (CH), 124.6 (CH), 127.3 (Cquat), 130.0
(CH), 133.8 (CH), 137.3 (Cquat), 138.8 (Cquat), 140.0 (Cquat), 141.2
(Cquat), 148.2 (Cquat), 151.9 (Cquat). MALDI-MS: m/z = 401.1 [MH+].
̃
IR (solid): ν 2207 (w), 1520 (m), 1489 (w), 1441 (w), 1423 (w), 1371
(m), 1341 (w), 1306 (w), 1285 (w), 1148 (w), 1117 (m), 1084 (m),
1013 (w), 997 (w), 937 (w), 908 (w), 874 (m), 837 (w), 773 (m), 741
(s), 683 (s), 658 (w), 624 (m), 611 (w). Anal. Calcd for C29H19N3
(409.5): C, 85.06; H, 4.68; N, 10.26. Found: C, 84.93; H, 4.49; N, 10.38.
General Procedure for the Three-Component Synthesis of
3-Ethynylquinoxalines 7. A 2.00 mmol portion of glyoxylic acid 7 in
dry 1,4-dioxane (2.5 mL/mmol) was placed under argon or nitrogen
atmosphere in a screw-cap Schlenk tube and degassed with argon or
nitrogen (for experimental details, see Table 8). Then, oxalyl chloride
̃
IR (solid): ν 3686 (w), 2970 (w), 2959 (w), 2901 (w), 2357 (w), 2330
(w), 1614 (w), 1516 (s), 1476 (m), 1458 (w), 1418 (w), 1408 (w),
1371 (m), 1337 (s), 1317 (w), 1287 (m), 1242 (m), 1215 (m), 1194
(m), 1159 (w), 1121 (w), 1090 (m), 1070 (m), 1057 (m), 1018 (w),
959 (w), 901 (m), 868 (m), 839 (s), 818 (m), 793 (m), 748 (s), 729
(s), 702 (m), 658 (m), 638 (m), 619 (m). Anal. Calcd for
C22H20N4O2Si (400.5): C, 65.98; H, 5.03; N, 13.99. Found: C,
65.76; H, 5.15; N, 14.08.
Table 8. Experimental Details for the Three-Component
Synthesis of 2-Substituted 3-Ethynylquinoxalines 7
a
b
entry
glyoxylic acid 6
3-ethynylquinoxaline 7 (yield, %)
3-(1-Methyl-1H-indol-3-yl)-2-[(triisopropylsilyl)ethynyl]pyrido-
[2,3-b]pyrazine and 2-(1-Methyl-1H-indol-3-yl)-3-[(triisopropylsilyl)-
ethynyl]pyrido[2,3-b]pyrazine (5v). Orange resin (358 mg, 72%). Rf =
0.32 (petroleum ether/ethyl acetate 3:1). Mp: 99 °C. 1H NMR
(CDCl3, 300 MHz): isomer ratio =6.5:1; δ 1.17−1.27 (m, 21 H), 3.88
(s, 3 H), 7.27−7.47 (m, 4 H), 7.61 (dd, J = 8.3 Hz, J = 4.2 Hz, 1 H),
8.42 (dd, J = 8.3 Hz, J = 1.9 Hz, 1 H), 8.77 (s, 1 H), 8.77−8.82 (m, 1
H), 9.02 (dd, J = 4.2 Hz, J = 1.9 Hz, 1 H); additional signals for the
minor isomer: δ 3.84 (s, 3 H). 13C NMR (CDCl3, 75 MHz): δ 11.3
(CH), 18.7 (CH3), 33.3 (CH3), 100.1 (Cquat), 106.0 (Cquat), 109.5
(CH), 111.7 (Cquat), 121.7 (CH), 123.0 (CH), 123.1 (CH), 125.3
(CH), 127.4 (Cquat), 133.5 (CH), 136.5 (Cquat), 137.1 (CH), 137.3
(Cquat), 139.2 (Cquat), 148.1 (Cquat), 151.3 (Cquat), 151.4 (CH).
Additional signals for the minor isomer: δ 33.6 (CH3), 109.8 (CH),
122.6 (CH), 123.7 (CH), 140.2 (CH). EI + MS (m/z): 441 (36), 440
(M+, 100), 398 (13), 397 ([M − C3H7]+, 41), 356 (13), 355 (41), 354
([M − (C3H7)2]+, 8), 327 (28), 318 (19), 325 (12), 311 ([M −
(C3H7)3]+, 47), 163 (12), 158 (21), 156 (15), 155 (12), 135 (13).
1
2
3
4
300 mg (2.00 mmol) of 6a
384 mg (2.00 mmol) of 6b
280 mg (2.00 mmol) of 6c
312 mg (2.00 mmol) of 6d
515 mg (85%) of 7a
178 mg (26%) of 7b
178 mg (30%) of 7c
427 mg (69%) of 7d
a
b
All compounds were prepared on a 2.00 mmol scale. Yields after
chromatography on silica gel.
(0.18 mL, 2.00 mmol, 1.0 equiv) was added dropwise to the reaction
mixture. The mixture was stirred at room temperature (water bath) for
5 min and then at 50 °C for 4 h. Thereafter, the mixture was cooled to
room temperature (water bath, 5 min). Then, CuI (20 mg, 0.1 mmol,
5 mol %), trimethylsilylacetylene (2b) (0.28 mL, 2.00 mmol, 1 equiv),
and dry triethylamine (0.84 mL, 6.00 mmol, 3.0 equiv) were
successively added to the reaction mixture, and stirring at room
temperature was continued for 15 h. Then, 2 mL of methanol, 216 mg
of 1,2-diaminobenzene (4a) (2.00 mmol, 1.0 equiv), and 2 mL of
acetic acid were added successively, and the mixture was stirred at
̃
IR (solid): ν 2941 (w), 2887 (w), 2862 (w), 1609 (w), 1591 (w),
M
dx.doi.org/10.1021/jo4025978 | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
50 °C for 3 h. Then, 10 mL of water was added, the phases were
separated, and the aqueous phase was extracted with dichloromethane
(3 × 5 mL/10 mL, monitored by TLC). The combined organic layers
were dried with anhydrous sodium sulfate. The reaction mixture was
absorbed onto Celite in vacuo and purified chromatographically on silica
gel with solvent mixtures of petroleum ether (boiling range 40−60 °C) and
ethyl acetate or dichloromethane to give the 3-ethynylquinoxalines 7.
2-Phenyl-3-[(trimethylsilyl)ethynyl]quinoxaline (7a). Colorless oil
(515 mg, 85%). Rf = 0.28 (petroleum ether/ethyl acetate 20:1). 1H NMR
(CDCl3, 300 MHz): δ 0.22 (s, 9 H), 7.47−7.54 (m, 3 H), 7.72−7.79
(m, 2 H), 8.03−8.15 (m, 4 H). 13C NMR (CDCl3, 75 MHz): δ −0.71
(CH3), 102.1 (Cquat), 102.7 (Cquat), 127.9 (CH), 128.8 (CH), 129.2 (CH),
129.6 (CH), 129.7 (CH), 130.2 (CH), 130.8 (CH), 137.3 (Cquat), 137.5
(Cquat), 140.75 (Cquat), 140.76 (Cquat), 154.9 (Cquat). EI + MS (m/z): 303
(12), 302 (M+, 47), 301 (61), 288 (25), 287 ([M − CH3]+, 100), 272
ASSOCIATED CONTENT
■
S
* Supporting Information
Experimental data on the optimization study for the synthesis
of ynediones 3. Selected 1H and 13C NMR spectra of
compounds 5a−x and 7a−d, selected absorption and emission
spectra of compounds 5a, 5d, 5h, 5m, and 5r. Crystallographic
data of the X-ray structure analyses of compounds 5d, 5n, 5q,
and 5x. Computational data and TD-DFT computed UV/vis
spectra of the quinoxalines 5a, 5d, 5h, 5m, and 5r. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: thomasjj.mueller@uni-duesseldorf.de.
Notes
([M − (CH3)2]+, 6), 271 (11), 257 (22). IR (solid): ν
̃
3061 (w), 2959
(w), 2897 (w), 2160 (w), 1609 (w), 1557 (m), 1530 (w), 1477 (w), 1393
(w), 1335 (m), 1308 (m), 1285 (w), 1250 (m), 1217 (w), 1188 (w), 1130
(m), 1123 (w), 1076 (w), 1036 (w), 997 (w), 912 (w), 839 (2), 820 (m),
758 (s), 729 (m), 692 (s), 635 (m), 606 (m). HR-MS: mass calcd for
C19H18N2Si−H+ 303.13175, found 303.13120.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
2-Mesityl-3-[(trimethylsilyl)ethynyl]quinoxaline (7b). Colorless
Financial support of the Fonds der Chemischen Industrie,
Frankfurt (Main), is gratefully acknowledged.
solid (178 mg, 26%). Rf = 0.32 (petroleum ether/ethyl acetate
1
20:1). Mp: 101 °C. H NMR (CDCl3, 300 MHz): δ 0.03 (s, 9 H),
2.01 (s, 6 H), 2.34 (s, 3H), 6.95 (s, 2 H), 7.74−7.81 (m, 2 H), 8.08−
8.16 (m, 2 H). 13C NMR (CDCl3, 75 MHz): δ −0.9 (CH3), 19.7
(CH3), 21.1 (CH3), 101.3 (Cquat), 102.0 (Cquat), 128.1 (CH), 129.0
(CH), 129.3 (CH), 130.2 (CH), 130.5 (CH), 134.3 (Cquat), 135.8
(Cquat), 138.3 (Cquat) 139.8 (Cquat) 140.78 (Cquat), 140.83 (Cquat),
158.1 (Cquat). EI + MS (m/z): 345 (30), 344 (M+, 100), 343 (38), 330
(13), 329 ([M − CH3]+, 47), 157 (14), 147 (58), 119 (C9H11+, 13).
REFERENCES
■
(1) (a) Kelley, T. W.; Baude, P. F.; Gerlach, C.; Ender, D. E.; Muyres,
D.; Haase, M. A.; Vogel, D. E.; Theiss, S. D. Chem. Mater. 2004, 16,
4413−4422. (b) Forrest, S. R.; Thompson, M. E. Chem. Rev. 2007,
107, 923−925.
(2) For diversity-oriented syntheses of functional π-systems, see:
̃
IR (solid): ν 2959 (w), 2918 (w), 2853 (w), 2162 (w), 1652 (w), 1613
(a) Muller, T. J. J. In Functional Organic Materials. Syntheses, Strategies,
̈
(m), 1589 (w), 1556 (w), 1539 (m), 1456 (w), 1433 (w), 1379 (w),
1329 (m), 1314 (w), 1192 (m), 1157 (w), 1130 (m), 1119 (m), 1065
(w), 1036 (w), 1013 (w), 1001 (w), 986 (w), 949 (w), 912 (w), 839
(s), 812 (m), 766 (s), 739 (m), 700 (w), 669 (m), 650 (m), 631 (m),
608 (m). Anal. Calcd for C22H24N2Si (344.5): C, 76.70; H, 7.02; N,
8.13. Found: C, 76.69; H, 6.80; N, 7.83.
and Applications; Muller, T. J. J., Bunz, U. H. F., Eds.; Wiley:
̈
Weinheim, 2007; pp 179−223. For the concept of diversity oriented
synthesis, see, e.g.: (b) Burke, M. D.; Schreiber, S. L. Angew. Chem.
2004, 116, 48−60; Angew. Chem., Int. Ed. 2004, 43, 46−58.
(3) (a) Sunderhaus, J. D.; Martin, S. F. Chem.Eur. J. 2009, 15,
1300−1308. (b) Isambert, N.; Lavilla, R. Chem.Eur. J. 2008, 14,
8444−8454. (c) Orru, R. V. A.; de Greef, M. Synthesis 2003, 1471−
1499. (d) Bonne, D.; Coquerel, Y.; Constantieux, T.; Rodriguez, J.
Tetrahedron: Asymmetry 2010, 21, 1085−1109.
2-(Furan-2-yl)-3-[(trimethylsilyl)ethynyl]quinoxaline (7c). Beige
solid (178 mg, 30%). Rf = 0.26 (petroleum ether/ethyl acetate
10:1). Mp: 78 °C. 1H NMR (CDCl3, 300 MHz): δ 0.37 (s, 9 H), 6.62
(dd, J = 3.6 Hz, J = 1.8 Hz, 1 H), 7.66−7.79 (m, 3 H), 7.88 (dd, J = 3.6
Hz, J = 0.7 Hz, 1 H), 8.02−8.08 (m, 1 H), 8.10−8.16 (m, 1 H). 13C
NMR (CDCl3, 75 MHz): δ −0.6 (CH3), 102.6 (Cquat), 102.7 (Cquat),
111.9 (CH), 115.6 (CH), 128.9 (CH), 129.1 (CH), 130.1 (CH),
131.2 (CH), 134.8 (Cquat), 140.2 (Cquat), 140.5 (Cquat), 143.9 (Cquat),
145.4 (CH), 149.8 (Cquat). EI + MS (m/z): 293 (19), 292 (M+, 80),
278 (24), 277 ([M − (CH3)]+, 100), 262 ((M − (CH3)2)+, 4), 247 ((M
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− (CH3)3)+, 19). IR (solid): ν
̃
3142 (w), 3123 (w), 2955 (w), 2924 (w),
1095−1108. (b) Muller, T. J. J. Top. Heterocycl. Chem. 2010, 25, 25−
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94.
2899 (w), 2853 (w), 2164 (w), 1611 (w), 1574 (w), 1522 (w), 1472
(w), 1451 (w), 1404 (w), 1335 (m), 1314 (w), 1252 (w), 1225 (w),
1196 (m), 1163 (w), 1132 (m), 1123 (w), 1083 (w), 1040 (w), 1007
(w), 962 (w), 923 (w), 885 (w), 841 (s), 800 (w), 760 (s), 739 (m),
700 (w), 664 (w), 633 (m) 621 (m). Anal. Calcd for C17H16N2OSi
(292.4): C, 69.83; H, 5.52; N, 9.58. Found: C, 69.58; H, 5.48; N, 9.36.
2-(Thiophene-2-yl)-3-[(trimethylsilyl)ethynyl]quinoxaline (7d).
Light yellow solid (427 mg, 69%). Rf = 0.30 (petroleum ether/ethyl
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(b) Toure, B. B.; Hall, D. G. Chem. Rev. 2009, 109, 4439−4486.
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1
(8) (a) Bay, S.; Villnow, T.; Ryseck, G.; Rai-Constapel, V.; Gilch, P.;
Muller, T. J. J. ChemPlusChem 2013, 78, 137−141. (b) Cinar, R.;
Nordmann, J.; Dirksen, E.; Muller, T. J. J. Org. Biomol. Chem. 2013, 11,
acetate 25:1). Mp: 81 °C. H NMR (CDCl3, 300 MHz): δ 0.37 (s, 9
̈
H), 7.18 (dd, J = 5.1 Hz, J = 3.9 Hz, 1 H), 7.56 (dd, J = 5.1 Hz, J = 1.0
Hz, 1 H), 7.65−7.76 (m, 2 H), 8.00−8.07 (m, 2 H), 8.55 (dd, J = 3.8
Hz, J = 1.0 Hz, 1 H). 13C NMR (CDCl3, 75 MHz): δ −0.6 (CH3),
102.6 (Cquat), 103.1 (Cquat), 127.8 (CH), 128.7 (CH), 128.8 (CH),
129.9 (CH), 130.2 (CH), 130.4 (CH), 131.0 (CH), 134.8 (Cquat),
140.3 (Cquat), 140.6 (Cquat) 141.8 (Cquat) 147.6 (Cquat). EI + MS
(m/z): 309 (15), 308 (M+, 54), 307 (26), 293 ([M − (CH3)]+, 100),
̈
2597−2604. (c) Dostert, C.; Wanstrath, C.; Frank, W.; Muller, T. J. J.
̈
Chem. Commun. 2012, 48, 7271−7273. (d) Meyer, T.; Ogermann, D.;
Pankrath, A.; Kleinermanns, K.; Muller, T. J. J. J. Org. Chem. 2012, 77,
̈
3704−3715.
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5604−5606.
̃
263 (20). IR (solid): ν 2957 (w), 1526 (w), 1474 (w), 1427 (w), 1335
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(m), 1248 (m), 1230 (w), 1217 (w), 1180 (w), 1134 (w), 1082 (w),
1058 (w), 947 (w), 912 (w), 843 (s), 810 (m), 759 (s), 739 (m), 716
(s), 708 (s), 662 (w), 631 (m), 617 (m). Anal. Calcd for C17H16N2SSi
(308.5): C, 66.19; H, 5.23; N, 9.08. Found: C, 65.97; H, 5.43; N, 8.90.
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N
dx.doi.org/10.1021/jo4025978 | J. Org. Chem. XXXX, XXX, XXX−XXX

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