Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

Article abstract of DOI:10.3762/bjoc.15.262

Starting from substituted alkynones, α-pyrones and/or 1H-pyridines were generated in a Michael addition–cyclocondensation with ethyl cyanoacetate. The peculiar product formation depends on the reaction conditions as well as on the electronic substitution

Full text of DOI:10.3762/bjoc.15.262

Emission solvatochromic, solid-state and
aggregation-induced emissive α-pyrones and
emission-tuneable 1H-pyridines by Michael
addition–cyclocondensation sequences
Natascha Breuer1, Irina Gruber2, Christoph Janiak2 and Thomas J. J. Müller*1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2019, 15, 2684–2703.
1Heinrich-Heine Universität Düsseldorf, Institut für Organische
Chemie und Makromolekulare Chemie, Universitätsstraße 1, D-40225
Düsseldorf, Germany and 2Heinrich-Heine Universität Düsseldorf,
Institut für Anorganische Chemie und Strukturchemie,
Universitätsstraße 1, D-40225 Düsseldorf, Germany
doi:10.3762/bjoc.15.262
Received: 16 July 2019
Accepted: 24 October 2019
Published: 12 November 2019
Email:
This article is part of the thematic issue "Dyes in modern organic
chemistry".
Thomas J. J. Müller* - ThomasJJ.Mueller@uni-duesseldorf.de
* Corresponding author
Guest Editor: H. Ihmels
Keywords:
© 2019 Breuer et al.; licensee Beilstein-Institut.
License and terms: see end of document.
cyclocondensation; DFT calculations; fluorescence; heterocycles;
1H-pyridines; α-pyrones
Abstract
Starting from substituted alkynones, α-pyrones and/or 1H-pyridines were generated in a Michael addition–cyclocondensation with
ethyl cyanoacetate. The peculiar product formation depends on the reaction conditions as well as on the electronic substitution
pattern of the alkynone. While electron-donating groups furnish α-pyrones as main products, electron-withdrawing groups predomi-
nantly give the corresponding 1H-pyridines. Both heterocycle classes fluoresce in solution and in the solid state. In particular,
dimethylamino-substituted α-pyrones, as donor–acceptor systems, display remarkable photophysical properties, such as strongly
red-shifted absorption and emission maxima with daylight fluorescence and fluorescence quantum yields up to 99% in solution and
around 11% in the solid state, as well as pronounced emission solvatochromism. Also a donor-substituted α-pyrone shows pro-
nounced aggregation-induced emission enhancement.
Introduction
A high sensitivity and precise tuneability of fluorescence colors achieved [4]. Small molecule organic fluorophores are particu-
are prerequisites for the application of fluorescent substances in larly advantageous due to the potential of a tailored fine-tuning
chemistry, medicine and materials science [1]. With this respect of their photophysical properties through synthetic modifica-
emissive small molecules [2], fluorescent proteins [3], and tions [5]. Based on their structural features, functionalized
quantum dots have received considerable attention and remark- organic chromophores, containing N-, O- or S-atoms, are
able progress in their synthesis and photophysics has been increasingly used in OLEDs [6-10] and LCDs [11-13] of mobile
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phones [14]. Fluorescent compounds often intensively emit in 1,2-diaroylacetylenes with ethyl cyanoacetate [27], similar to
solution but only weakly or not in the solid state [15]. Dyes related studies with dialkyl malonates [28]. Here, we report on
which fluoresce both in the solid state and in solution are still effects of base and temperature on Michael addition–cyclocon-
relatively rare, due to the fact that often molecular aggregation densation sequences in the formation of α-pyrones and/or
in the solid state causes fluorescence quenching [16].
1H-pyridines starting from diversely substituted alkynones and
cyanoethylacetate. This bifurcating domino process furnishes
In recent years, we have coined diversity-oriented syntheses of small chromophore libraries which were characterized by pho-
functional chromophores by multicomponent strategies [17,18], tophysical studies (absorption and emission spectroscopy) and
opening accesses to substance libraries for systematic studies of the studies on the electronic structure were accompanied by
structure–property relationships on fluorophores [19], in partic- TD-DFT calculations for assigning the dominant longest-wave-
ular on aggregation-induced emissive polar dyes [20]. Concep- length absorption bands.
tually, many of these consecutive multicomponent syntheses
rely on transition-metal-catalyzed heterocyclic syntheses [21].
By virtue of catalytic generation of alkynones [22] we have Synthesis and tentative mechanism
recently disclosed consecutive alkynylation–Michael addi- Recently, we reported a straightforward access to α-pyrones
tion–cyclocondensation (AMAC) multicomponent syntheses of through a consecutive alkynylation–Michael addition–cyclo-
Results and Discussion
α-pyrones [23].
condensation (AMAC) multicomponent synthesis [23]. The
reaction can be rationalized by a Sonogashira coupling between
While most α-pyrones neither fluoresce in solution nor in the an acid chloride and a terminal alkyne furnishing an alkynone,
solid state specific substitution patterns have been identified for which is transformed without isolation by addition of dialkyl
fluorophore design for this heterocyclic family. Tominaga and malonates in a Michael addition–cyclocondensation to form
co-workers synthesized a series of α-pyrone derivatives with α-pyrones (Scheme 1).
emission maxima between 400 and 675 nm in the solid state
and between 486 and 542 nm in chloroform [16,24-26], includ- With this sequence in hand, we envisioned the variation of
ing fluorescence quantum yields as high as 95% in solution and CH-acidic esters to generate differently 3-substituted α-pyrones.
58% in the solid state [16,24]. While these fluorophores were For introducing a cyano substituent we employed benzoyl chlo-
synthesized by cyclocondensation with ketene dithioacetals and ride (1a), phenylacetylene (2a), and ethyl cyanoacetate (4)
substituted acetophenones other cyano-containing derivatives within the AMAC sequence (Scheme 2). Surprisingly, the
became accessible by desymmetrizing cyclocondensation of desired α-pyrone was not isolated, but two other compounds
Scheme 1: Consecutive three-component alkynylation–Michael addition–cyclocondensation (AMAC) synthesis of α-pyrones from acid chlorides, ter-
minal alkynes and dialkyl malonates.
Scheme 2: Consecutive pseudo-four-component alkynylation–Michael addition–cyclocondensation (AMAC) synthesis of 1H-pyridines 5a and an
aniline derivative.
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were detected. On the one hand a 1H-pyridine derivative 5a
(2% yield) and on the other hand an aniline derivative with two
ester groups (4% yield). Both compounds indicate that two mol-
ecules of ethyl cyanoacetate (4) were incorporated in the final
structure.
Table 1: Optimization of the cyclization step of 1,5-diacyl-5-hydroxypy-
razoline 5b.a
Entry Base (equiv)
Compound Compound
5a (yield)b 6a (yield)b
1
2
3
4
5
6c
7b
Na2CO3∙10H2O (0.80)
20%
8%
32%
26%
3%
50%
64%
–
Na2CO3∙10H2O (1.0)
Na2CO3∙10H2O (1.5)
Na2CO3∙10H2O (2.0)
Na2CO3 (0.80)
Na2CO3 (0.80)
Na2CO3 (1.4)
With an increased amount of ethyl cyanoacetate the yield of
both products could be increased. By the addition of ethanol as
a cosolvent in the second step of the sequence, 1H-pyridine 5a
could be isolated in 30% yield, while the aniline derivative was
not formed (Scheme 3).
–
41%
52%
66%
22%
9%
aAll reactions were carried out on a 0.500 mmol scale
(c0(3a) = 0.50 M, c0(4) = 2.0 M; ball yields refer to isolated and purified
products; cadditional water (5.6 equiv).
There are only a few known methods for the synthesis of this
kind of 1H-pyridines. In a cyclocondensation, starting from 1,3-
dicarbonyl compounds, Elnagdi and co-workers synthesized
1H-pyridines with an additional cyano substituent in the 3-posi- With either 0.8 or 1.0 equiv of Na2CO3·10H2O α-pyrone 6a is
tion [29]. Most syntheses generating 1H-pyridines make use of formed as the main product (50–64%), while 1H-pyridine 5a
ethyl cyanoactate as a starting material. It can react with itself can also be isolated in around 15% yield (Table 1, entries 1 and
and forms a dimer by selfcondensation, catalyzed by transition 2). By increasing the amount of Na2CO3·10H2O, exclusively
metals [30,31].
1H-pyridine 5a can be isolated in low yield (Table 1, entries 3
and 4). Using anhydrous sodium carbonate α-pyrone 6a is again
Intrigued by the unusual pseudo-four-component AMAC syn- formed as the main product in 41% yield, but the yield of
thesis we investigated the reaction conditions of the terminal 1H-pyridine 5a drops to 3% (Table 1, entry 5). By the addition
Michael addition–cyclocondensation step starting from of water, the yield of 6a could be increased (Table 1, entries 6
alkynone 3a. By varying the amount of the base we could and 7).
observe the formation of 1H-pyridine 5a, but also of α-pyrone
6a (Scheme 4, Table 1), similarly to the reaction of compound 4 Next we evaluated the use of a mixture of two bases, sodium
with 1,2-diaroylacetylenes [28].
carbonate and sodium acetate, and water (Table 2). With
Scheme 3: Consecutive pseudo-four-component alkynylation–Michael addition–cyclocondensation (AMAC) synthesis of 1H-pyridines 5a from acid
chlorides 1, terminal alkynes 2 and ethyl cyanoacetate (4).
Scheme 4: Model system for the optimization of the Michael addition–cyclocondensation reaction step to 1H-pyridine 5a or/and α-pyrone 6a.
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1H-pyridine 5a in 23% yield (Table 2, entry 6). It seems to be
important that both bases and water are present, but neither a
reduction nor an increase of the amount of water increased the
yields of 1H-pyridine 5a (Table 2, entries 7–9). The increase of
neither sodium carbonate (Table 2, entry 10) nor sodium acetate
(Table 2, entry 11) caused an increase in yields.
Table 2: Optimization of the formation of 1H-pyridine 5a or/and
α-pyrone 6a in the Michael addition–cyclocondensation reaction with
Na2CO3, NaOAc and water.a
Entry Na2CO3 NaOAc H2O
Compound Compound
[equiv]
[equiv] [equiv] 5a (yield)b 6a (yield)b
1
0.80
0.80
0.80
0.80
–
0.60
0.60
0.60
0.60
0.60
0.60
0.60
0.60
0.60
0.60
0.80
5.6.
5.6
5.6
–
56%
26%
56%
44%
26%
23%
40%
40%
38%
45%
43%
–
–
–
–
28%
–
–
20%
28%
–
2c
3d
4
5
6
7
8
9
10
11
Only lowering the reaction temperature to 20 °C α-pyrone 6a
was isolated as the main product in 78% yield and 1H-pyridine
5a was obtained in only 7% yield (Scheme 5).
–
–
5.6
2.8
8.4
11
5.6
5.6
0.80
0.80
0.80
1.0
Since base(s) and reaction temperature exert a significant
impact on which heterocyclic compound is formed, we also
tried to change the electronic nature of the starting material.
Therefore, an electron-donating substituent was introduced in
the alkynone 3b and the reaction was performed at 75 °C. To
our surprise, we only could isolate α-pyrone 6b (Scheme 6).
0.80
–
aAll reactions were carried out on a 0.500 mmol scale
(c0(3a) = 0.50 M, c0(4) = 2.0 M; ball yields refer to isolated and purified
products; cc0(4) = 1.0 M; dadditional 4.0 equiv of ethyl cyanoacetate
(4) after 2 h.
However, when we introduced an electron-withdrawing group
1H-pyridine 5b was the only product (Scheme 7).
0.80 equiv of sodium carbonate, 0.60 equiv of sodium acetate
and 5.6 equiv of water 1H-pyridine 5a could be isolated in 56% For elucidating whether 1H-pyridine 5a is formed from
yield. Decreasing the amount of ethyl cyanoacetate (4) the α-pyrone 6a and ethyl cyanoacetate (4) a reaction between
yields drops (Table 2, entry 2), however, increasing the amount α-pyrone 6a and ethyl cyanoacetate (4) under the same reaction
of substrate 4 does not improve the yield (Table 2, entry 3). The conditions as for the 1H-pyridine from alkynone 3a was con-
exclusion of water only causes a decrease in yield (Table 2, ducted, but only starting material could be isolated. Another
entry 4). With sodium acetate as the only base, both 1H-pyri- option for the formation of the 1H-pyridine 5a was envisioned
dine 5a and α-pyrone 6a are formed in ca. 25% yield each by an in situ generation of a dimer of ethyl cyanoacetate (4).
(Table 2, entry 5). Sodium acetate with additional water gives The dimer 7 can be synthesized by iridium catalysis [30]. With
Scheme 5: Formation of α-pyrone 6a and 1H-pyridine 5a at 20 °C.
Scheme 6: Formation of α-pyrone 6a starting from alkynone 3b having an electron-donating substituent.
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Scheme 7: Formation of 1H-pyridine 5b starting from alkynone 3d having an electron-withdrawing substituent.
dimer 7 in hand, we performed the reaction at 75 °C for 16 h, In the first attempt, alkynone 3a was added after 2 h. 1H-Pyri-
but we only could isolate 1H-pyridine 8a, which still contains dine 5a was isolated in 53% yield (Table 3, entry 1), indicating
an ester group (Scheme 8). Therefore, the in situ formation of that the time of addition of the alkynone is not relevant within
the dimer starting from the alkynone 3a and ethyl cyanoacetate the first two hours of the reaction. However, if alkynone 3a was
(4) was excluded for the formation of the 1H-pyridine 5a.
added after 6 h α-pyrone 6a was the main product and 1H-pyri-
dine 5a could only be isolated in 5% yield (Table 3, entry 2).
While the in situ generation of dimer 7 does not happen during Upon the addition of alkynone 3a after 24 h, both 1H-pyridine
the formation of 1H-pyridine 5a, we examined the reaction be- 5a and α-pyrone 6a were isolated in only around 3% yield. This
tween ethyl cyanoacetate (4) and the optimized base system by finding supports that within the first two hours ethyl cyano-
adding alkynone 3a to the reaction after different times acetate (4) is consumed and thereafter the ethyl cyanoacetate
(Table 3).
concentration is just too low for the formation of 1H–pyridine
Scheme 8: Formation of 1H-pyridine 8a by Michael addition–cyclocondensation reaction.
Table 3: Influence of the reaction time on the self-condensation of ethyl cyanoacetate (4) in the presence of the optimized base system.a
Entry
t1
t2
Compound 5a (yield)b
Compound 6a (yield)b
1
2
3
2 h
6 h
24 h
16 h
16 h
16 h
53%
5%
3%
–
46%
2%
aAll reactions were carried out on a 0.500 mmol scale (c0(3a) = 0.50 M, c0(4) = 2.0 M; ball yields refer to isolated and purified products.
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5a, therefore α-pyrone 6a is formed. At longer initial reaction entry 10). For electronically unsymmetrically substituted
times (6 and 24 h) there is no ethyl cyanoacetate (4) left for the alkynones 3 the product formation depends rather on the
formation of any product. Also, ethyl cyanoacetate (4) proba- strength of the employed electron-donating group. Whereas the
bly does not form dimer 7 because in that case under these p-anisyl substituent leads to the formation of 1H-pyridine
conditions 1H-pyridine 8a would have been detected.
(Table 4, entries 11 and 12), the N,N-dimethylaminophenyl sub-
stituent furnishes α-pyrone 6g (Table 4, entry 13).
Therefore, the tentative mechanistic rationale takes into account
that the formation of 1H-pyridine 5a rather proceeds via step- For synthesizing 1H-pyridine derivatives 8 with an electron-do-
wise condensation of alkynone 3 with two equivalents of ethyl nating group we employed the isolated dimer 7 and were able to
cyanoacetate (4) than by reaction with dimer 7 (Scheme 9).
isolate 1H-pyridines 8 in 52 and 34% yield (Scheme 10).
First, a molecule of ethyl cyanoacetate (4) attacks the Crystal structure of 1H-pyridine 5a
alkynone 3a in a Michael addition. A second molecule 4 The structure of 1H-pyridines 5 was further corroborated by a
then attacks the cyano substituent and an imine is formed. single crystal X-ray structure determination of compound 5a
The ester substituent of the initially reacted more electrophilic (Figure 1) [35]. In the single crystal the carboxyl ester group is
ethyl cyanoacetate (4) is presumably cleaved by a base-medi- oriented to the N–H and via a hydrogen bond. Solid-state
ated acyl cleavage furnishing directly 1H-pyridine 5a after pro- torsional/dihedral angles between the 4- and 6-positioned aryl
tonation.
rings differ especially for the 6-positioned phenyl ring with 27°
in the X-ray structure and 38° from calculation (for comparison
For examining the influence of the electronic nature of the to the DFT calculated ground state structure of 1H-pyridine 5a,
alkynone 3 on the product formation, a range of differently see chapter 12.3 in Supporting Information File 1). This is prob-
substituted alkynones 3 (for experimental details on their prepa- ably due to packing constraints from the involvement of the
ration, see chapters 2.1 and 2.2 in Supporting Information 6-phenyl ring in C-H···N [36-39] and C-H···π [40-49] interac-
File 1) bearing electron-donating and/or electron-withdrawing tions (Figure 2, for details, see Supporting Information File 1).
substituents were synthesized and employed in the cyclocon- It is noteworthy to mention that there are no significant π···π
densation step under the optimized reaction conditions [32-34]. interactions in the solid-state structure of 5a (for details, see
Alkynones 3b–e with only one electron-donating substituent Supporting Information File 1) [50-57].
furnish the corresponding α-pyrones 6b–e, while the alkynone
with a single electron-withdrawing substituent furnishes Photophysical properties
1H-pyridines 5b–e. Interestingly, the position of substitution on Photophysical properties of 1H-pyridines 5 and 8
the alkynone does not affect the outcome (Table 4, entries 2 and 1H-Pyridine derivatives 5 are yellow or orange compounds
6). Also, for alkynone 3j bearing an electron-donating substitu- under daylight (Figure 3, top) and fluoresce in solution
ent on either aryl ring, α-pyrone 6f is formed likewise (Table 4, (Figure 3, center) and in the solid state (Figure 3, bottom).
Scheme 9: Mechanistic rationale for the formation of the 1H-pyridine 5a.
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Table 4: Michael addition–cyclocondensation synthesis of 1H-pyridine 5 or α-pyrone 6.
Entry Alkynone 3
1H-Pyridine 5a
α-Pyrone 6a
1
3a (R1 = Ph, R2 = Ph)
5a (R1 = Ph, R2 = Ph, 56%)
–
2
3
4
5
6
7
8
9
3b (R1 = p-MeOC6H4, R2 = Ph)
3c (R1 = p-Me2NC6H4, R2 = Ph)
3d (R1 = p-F3CC6H4, R2 = Ph)
3e (R1 = p-NCC6H4, R2 = Ph)
3f (R1 = Ph, R2 = p-MeOC6H4)
3g (R1 = Ph, R2 = p-Me2NC6H4)
3h (R1 = Ph, R2 = p-F3CC6H4)
3i (R1 = Ph, R2 = p-NCC6H4)
–
–
6b (R1 = p-MeOC6H4, R2 = Ph; 70%)
6c (R1 = p-Me2NC6H4, R2 = Ph, 12%)
–
–
6d (R1 = Ph, R2 = p-MeOC6H4, 82%)
6e (R1 = Ph, R2 = p-Me2NC6H4, 62%)
–
–
5b (R1 = p-F3CC6H4, R2 = Ph, 22%)
5c (R1 = p-NCC6H4, R2 = Ph, 20%)
–
–
5d (R1 = Ph, R2 = p-F3CC6H4, 25%)
5e (R1 = Ph, R2 = p-NCC6H4, 2%)
10
3j (R1 = p-MeOC6H4, R2 =
p-MeOC6H4)
–
6f (R1 = p-MeOC6H4, R2 = p-MeOC6H4, 45%)
11
12
13
14
3k (R1 = p-MeOC6H4, R2 =
p-F3CC6H4)
3l (R1 = p-F3CC6H4, R2 =
p-MeOC6H4)
3m (R1 = p-F3CC6H4, R2 =
p-Me2NC6H4)
3n (R1 = 2-thienyl, R2 = Ph)
5f (R1 = p-MeOC6H4, R2 =
p-F3CC6H4, 37%)
5g (R1 = p-F3CC6H4, R2 =
p-MeOC6H4,, 40%)
–
–
–
6g (R1 = p-F3CC6H4, R2 = p-Me2NC6H4, 71%)
5h (R1 = 2-thienyl, R2 = Ph, 51%)
–
aAll yields refer to isolated and purified products.
Scheme 10: Formation of 1H-pyridine 8a from alkynone 3b and dimer 7.
Therefore, the photophysical properties were studied by absorp- group at the 4 or 6-aryl substituent does not affect the absorp-
tion and emission spectroscopy (Figure 4, Table 5).
tion energies. This situation changes to a minor extent upon
placing an additional donor substituent at the remaining phenyl
All compounds show three absorption maxima at around substituent (Table 5, entries 6 and 7). A thienyl substituent
275, 320 and 430 nm, where the longest wavelength instead of a phenyl substituent causes a redshift of the longest
absorption maxima exhibit extinction coefficients of around wavelength absorption maximum (Table 5, entries 1 and 8).
9500 L·mol−1·cm−1 (Table 5). Upon introducing electron-with-
drawing substituents on the aryl rings the longest wavelength Upon excitation at the longest wavelength absorption band
maxima shift bathochromically (Table 5, entries 2–5). The dichloromethane solutions of all compounds 5 fluoresce with
redshift qualitatively corresponds with the strength of the emission maxima at around 565 nm (Table 5, entries 2–5).
acceptor group (Table 5, entries 3 and 5). However, as can be Upon the introduction of electron-withdrawing substituents the
seen from entries 2–5 (Table 5), the placement of the acceptor maxima are shifted bathochromically, similarly as the absorp-
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Figure 1: Molecular structure of 1H-pyridine 5a (50% thermal ellip-
soids), showing the intramolecular N–H···O bond as dashed orange
line. H-bond details N1–H 0.90(2) Å, H···O1 1.87(2) Å, N1···O2
2.624(2) Å, O1–H···O2 140(1)°.
Figure 3: 1H-Pyridine derivatives 5 as solids under daylight (top),
under UV light (λexc = 365 nm, c(5) = 10−4 M) in dichloromethane solu-
tion (center), and under UV light (λexc = 365 nm) in the solid state
(bottom).
(Figure 5, Table 6), showing a similar behavior in the solid state
as in solution. The emission maximum of the unsubstituted
1H-pyridine 5a appears at 540 nm, while the CF3-substituted
1H-pyridine 5b emits bathochromically shifted at 604 nm.
In addition, both ester-substituted 1H-pyridines 8a and 8b also
possess interesting photophysical properties (Figure 6, Table 7).
Under daylight they are yellow and they fluoresce in solution
and in the solid state. The three absorption maxima are found at
around 270, 315 and 415 nm. The methoxy group in the spec-
trum of compound 8b only has a minor influence on the absorp-
tion maximum, however, slightly more on the emission
maximum. The fluorescence quantum yields Φf of both com-
pounds are lower than 1%.
Figure 2: Supramolecular C–H···N [36-39] and C–H···π [40-49] interac-
tions around the 6-positioned phenyl ring in 5a. Details of C–H···N
bond (dashed orange line) C11–H 0.95 Å, H···N2 2.61 Å, C11···N2
3.263(2) Å, C11–H···N2 127°. Symmetry transformations are i = 1−x,
1−y, 1−z; ii = x, 3/2−y, −1/2+z, iii = 1−x, −1/2+y, −1/2−z.
With the addition of the second ester group in the 3-position to
1H-pyridine 8a the fluorescence in the solid state appears to
shift to blue. If the phenyl substituent in the 4-position bears an
additional methoxy substituent the fluorescence of the 1H-pyri-
tion maxima, and the shift is qualitatively correlated with the dine 8b appears yellow again (Figure 7).
acceptor strength. In comparison, the introduction of another
electron-donating substituent does not significantly change the Photophysical properties of α-pyrones 6
luminescence characteristics (Table 5, entries 2, 4, 6 and 7). All α-pyrone derivatives 6 are yellow or red under daylight
The Stokes shifts fall in a range between 5000 and 6100 cm−1 (Figure 8, top) and some of them fluoresce in solution
and the fluorescence quantum yields of the 1H-pyridines 5 (Figure 8, center) and in the solid state (Figure 8, bottom).
account between 1 and 3%.
Therefore, the photophysical properties were studied by absorp-
tion and emission spectroscopy (Figure 9, Table 8).
Besides solution fluorescence all 1H-pyridines 5 also lumi-
nesce in the solid state (Figure 3, bottom). The emission All compounds show 2–4 absorption maxima and the shortest
maxima of two selected 1H-pyridines 5 were determined wavelength maxima appear at around 255 nm. The unsubsti-
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Figure 4: Selected normalized absorption (solid lines) and emission (dashed lines) spectra of 1H-pyridines 5a–e (recorded in dichloromethane at
T = 298 K).
Table 5: Photophysical properties of 1H-pyridines 5.
Entry Compound
R1
R2
λmax,abs [nm]a (ε [L·mol−1·cm−1])
λmax,em
[nm]b (Φf)c
Stokes shift
Δν [cm−1]
̃
1
2
3
4
5
6
7
8
5a
5b
5c
5d
5e
5f
Ph
Ph
Ph
Ph
281 (26100), 319 (17400), 418 (9800)
272 (27000), 326 (17500), 424 (8900)
280 (37600), 333 (17300), 431 (9500)
274 (32000), 321 (18100), 428 (10000)
283 (36000), 322 (15600), 434 (8600)
261 (26200), 306 (28400), 429 (10400)
260 (20300), 324 (43800), 420 (10000)
273 (21800), 308 (26700), 433 (9200)
545 (0.02)
565 (0.01)
585 (0.01)
565 (0.01)
579 (0.01)
557 (0.02)
562 (0.02)
560 (0.03)
5600
5600
6100
5700
5800
5400
6000
5200
p-F3CC6H4
p-NCC6H4
Ph
p-F3CC6H4
p-NCC6H4
p-F3CC6H4
p-MeOC6H4
Ph
Ph
p-MeOC6H4
p-F3CC6H4
2-thienyl
5g
5h
aRecorded in dichloromethane, T = 293 K, c(5) = 10−6 M; brecorded in dichloromethane, T = 293 K, c(5) = 10−7 M; cfluorescence quantum yields were
determined relative to coumarin153 (Φf = 0.54) as a standard in ethanol [58].
tuted α-pyrone 6a exhibits its longest wavelength maximum at In solution only N,N-dimethylaminophenyl-substituted deriva-
381 nm (Table 8, entry 1). A p-methoxyphenyl substituent in tives fluoresce (Figure 10). While the 6-substituted α-pyrone 6c
the 6-position causes a bathochromic shift (Table 8, entry 2), has a fluorescence maximum at 567 nm, the one for the regio-
whereas the same substituent in 4-position leads to a isomer 6e is shifted bathochromically to 634 nm (Table 8,
hypsochromic shift (Table 8, entry 4). Interestingly, p-methoxy- entries 3 and 5). Donor–acceptor substitution in positions 4 and
phenyl substituents at positions 4 and 6 split the longest absorp- 6 causes a further bathochromic shift to 673 nm (Table 8, entry
tion band into two maxima at 358 nm (arising from the 7). Most remarkably, the regioisomers 6c and 6e differ quite
p-methoxyphenyl substituent in the 4-position and at 400 nm significantly with respect to their fluorescence quantum yields
arising from the p-methoxyphenyl substituent in the 6-position) Φf. While chromophore 6e only emits with an efficiency of 1%,
(Table 8, entry 6). The introduction of a more strongly electron- the regioisomer 6c accounts for an extraordinarily high relative
donating substituent, such as N,N-dimethylaminophenyl, causes quantum yield of 99%.
a significant bathochromic shift (Table 8, entries 3 and 5).
Donor–acceptor substitution in positions 4 and 6 causes a Furthermore, the N,N-dimethylaminophenyl-derivative 6c
further bathochromic shift (Table 8, entry 7).
shows a pronounced emission solvatochromism (Figure 11,
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Beilstein J. Org. Chem. 2019, 15, 2684–2703.
Figure 5: Selected normalized emission spectra of 1H-pyridine 5a and 5b in the solid state at T = 298 K.
Table 9). While the polarity effect on the absorption maximum
is only minor within a range of the longest wavelength
maximum between 469 and 490 nm, the emission maximum is
shifted bathochromically with increasing solvent polarity in a
range from green fluorescence (529 nm) in toluene to red fluo-
rescence in DMSO (638 nm) (Figure 12). The observed posi-
tive emission solvatochromism is a consequence of a signifi-
cant change in the dipole moment from the electronic ground to
Table 6: Photophysical properties of 1H-pyridines 5a and 5b in the
solid state.
Compound
R1
R2
λmax,em [nm]a
5a
5b
H
CF3
H
H
540
604
aλexc = 420 nm.
Figure 6: Selected normalized absorption (solid lines) and emission (dashed lines) spectra of 1H-pyridines 8a and 8b (recorded in dichloromethane at
T = 298 K).
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Beilstein J. Org. Chem. 2019, 15, 2684–2703.
Table 7: Photophysical properties of 1H-pyridines 8.
Compound
R1
R2 λmax,abs [nm]a (ε [L·mol−1·cm−1])
λmax,em [nm]b (Φf)c Stokes shift Δ ν̃ [cm−1]
8a
8b
Ph
Ph 274 (20300), 324 (20100), 417 (7700)
Ph 261 (16200), 307 (31300), 419 (11000)
557 (<0.01)
565 (<0.01)
6000
6200
p-MeOC6H4
aRecorded in dichloromethane, T = 293 K, c(8) = 10−6 M; brecorded in dichloromethane, T = 293 K, c(8) = 10−7 M (λexc = 420 nm); cfluorescence
quantum yields were determined relative to coumarin153 (Φf = 0.54) as a standard in ethanol [58].
Figure 7: Solid-state luminescence of 1H-pyridines 5a, 8a and 8b
(λexc = 365 nm).
the vibrationally relaxed excited state [59]. Plotting Stokes
shifts Δν̃ against the orientation polarizabilities Δƒ of the
respective solvents (Lippert plot) [60] gives a reasonable linear
correlation with a moderate fit of r2 = 0.970 (Figure 13). The
orientation polarizabilities Δƒ were calculated according to
Equation 1
Figure 8: α-Pyrones 6 as solids under daylight (top), selected deriva-
tives under UV light (λexc = 365 nm, c(6) = 10−4 M) in dichloromethane
solution (center), and under UV light (λexc = 365 nm) in the solid state
(bottom).
Figure 9: Selected normalized absorption spectra of α-pyrones 6a, 6b, 6d, and 6e recorded in dichloromethane at T = 298 K.
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Beilstein J. Org. Chem. 2019, 15, 2684–2703.
Table 8: Photophysical properties of α-pyrones 6.
Entry Compound R1
R2
λmax,abs [nm]a (ε [L·mol−1·cm−1])
λmax,em
Stokes shift
[cm−1]
[nm]b (Φf)c Δν
̃
1
2
3
4
5
6
7
6a
6b
6c
6d
6e
6f
Ph
Ph
258 (15300), 311 (12800), 381 (18000)
254 (10300), 271 (11500), 312 (9600), 404 (21900)
294 (18800), 482 (47300)
–
–
–
–
p-MeOC6H4 Ph
p-Me2NC6H4 Ph
Ph
Ph
567 (0.99) 3100
–
p-MeOC6H4 258 (19700), 358 (30400)
p-Me2NC6H4 255 (25600), 289 (23300), 375 (39600), 453 (40600) 634 (0.01) 6300
–
p-MeOC6H4 p-MeOC6H4 254 (15000), 364 (25600), 400 (25100)
p-F3CC6H4 p-Me2NC6H4 251 (16200), 309 (13900), 372 (20200), 465 (21600) 673 (<0.01) 6600
–
–
6g
aRecorded in dichloromethane, T = 293 K, c(6) = 10−6 M; brecorded in dichloromethane, T = 293 K, c(6) = 10−7 M (λexc = 465 nm); cfluorescence
quantum yields were determined relative to DCM (Φf = 0.435) as a standard in ethanol [58].
Figure 10: Selected normalized absorption (solid lines) and emission (dashed lines) spectra of α-pyrones 6c, 6e, and 6g recorded in dichloro-
methane at T = 298 K.
(1)
where εr is the relative permittivity and n the optical refractive
index of the respective solvent.
The change in dipole from the ground to the excited state
can be calculated according to the Lippert–Mataga equation
(Equation 2)
(2)
Figure 11: Absorption (top) and fluorescence (bottom) of compound
6c with variable solvent polarity (left to the right: toluene, ethyl acetate,
acetone, DMF and DMSO, c(6c) = 10−4 M; λexc = 365 nm, handheld
UV lamp).
where ν̃abs represents the absorption and ν̃em the emission
maxima (in m−1), µE and µG are the dipole moments in the
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Beilstein J. Org. Chem. 2019, 15, 2684–2703.
Figure 12: Absorption (solid lines) and emission (dashed lines) spectra of α-pyrone 6c in five solvents of different polarity (recorded at T = 298 K).
Figure 13: Lippert plot for α-pyrone 6c (n = x, r2 = 0.970).
excited and ground state (in C·m), ε0 (8.8542·10−12 A·s/V·m) is All α-pyrones 6 fluoresce in the solid state (Figure 8, bottom)
the vacuum permittivity constant, h (6.6256·10−34 J·s) is the and for five selected α-pyrones 6 the emission maxima were de-
Planck’s constant, c (2.9979·1010 cm/s) is the speed of light and termined (Figure 14, Table 9). The fluorescence maximum of
a is the radius of the solvent cavity occupied by the molecules unsubstituted α-pyrone 6a lies at 499 nm and the maxima of the
(in m). The Onsager radius a, assuming a spherical dipole to ap- monomethoxy-substituted regioisomers 6b (540 nm) and 6d
proximate the molecular volume of the molecule in solution, (489 nm) appear at quite different energies, similar to their cor-
was estimated from the optimized ground-state structure of responding absorption maxima in solution. In comparison to
compound 6c obtained by DFT calculations. With an a value of α-pyrone 6a the introduction of two methoxy substituents in de-
5.46 Å, the change in dipole moment was calculated to 11.6 D rivative 6f results in a bathochromic shift to 526 nm. The solid-
(3.87·10−29 C·m).
state emission of N,N-dimethylaminophenyl derivative 6c
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Figure 14: Normalized emission spectra of selected α-pyrones 6a–d,f in the solid state at T = 298 K.
ratio of 80% aggregates are formed and the emission maximum
is shifted to 632 nm. The maximal relative intensity of 130 is
reached for a ratio of 85%, which is more intense than in pure
THF, therefore, an AIEE effect occurs. Further increasing the
water content slightly quenches the emission.
Table 9: Photophysical properties of selected α-pyrones 6 in the solid
state.
Compound
R1
R2
λmax,em [nm]a
6a
6b
6c
6d
6f
Ph
Ph
Ph
499
540
694b
489
526
p-MeOC6H4
p-Me2NC6H4 Ph
Ph
Computational studies
p-MeOC6H4
p-MeOC6H4
Computational studies on 1H-pyridines 5 and 8
For a further elucidation of the electronic structure the geome-
tries of the electronical ground-state structures of the
1H-pyridines 5 and 8 were optimized using Gaussian 09 with
the B3LYP functional [65-68] and the Pople 6-311G** basis set
p-MeOC6H4
aλexc = 380 nm; bλexc = 480 nm.
shows an enormous redshift to 694 nm. The solid-state fluores- [69], applying vacuum calculations as well as the polarizable
cence quantum yield Φf of compound 6c was determined to continuum model (PCM) with dichloromethane as a solvent
11%.
[70] (for details of the DFT calculations, see Supporting Infor-
mation File 1). The optimized geometries were verified by fre-
Interestingly, the α-pyrone 6e with the N,N-dimethylamino- quency analyses of the local minima. The electronic absorp-
phenyl substituent in 4-position only fluoresces weakly in solu- tions of the 1H-pyridines 5 and 8 were calculated on the level of
tion but shows a strong fluorescence in the solid state. This TDDFT theory employing the B3LYP functional and the Pople
finding suggests that by restricting intramolecular motion and 6-311G** basis set. The calculated absorption maxima are in
vibration, which enables radiation-less deactivation of the accordance with the experimentally determined maxima (for
excited state [61], an AIE (aggregation‐induced emission) or details, see Tables S7 and S8 in Supporting Information File 1).
AIEE (aggregation-induced enhanced emission), might become Most characteristically, for all 1H-pyridines 5 and 8 the longest
operative [62-64].
wavelength maxima representing the Franck–Condon S1 states
are characterized by HOMO–LUMO transitions and S2 states
The AIE or AIEE effect was assessed by measuring the emis- are represented by HOMO–LUMO+1 transitions.
sion spectra of α-pyrone 6e in THF/water at variable ratios
(Figure 15). In pure THF α-pyrone 6e displays an emission The computed Kohn–Sham frontier molecular orbitals show
maximum at 644 nm with a relative intensity of 54. The addi- that the coefficient density of the HOMO of the 1H-pyridines 5f
tion of water first quenches the fluorescence and at a water/THF and 5g with an electron-withdrawing and an electron-donating
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Beilstein J. Org. Chem. 2019, 15, 2684–2703.
Figure 15: Fluorescence of compound 6e in different THF/water fractions (top, λexc = 365 nm, handheld UV lamp) and I/I0 vs %H2O of α-pyrone 6e in
THF/water mixtures containing different water fractions (bottom, recorded at T = 298 K).
substituent is located on the 1H-pyridine core, the ester and 6 were optimized using Gaussian 09 with the B3LYP func-
cyano substituents and also on the electron-rich aryl substituent. tional [65-68] and the Pople 6-311G** basis set [69], applying
For the LUMO, the coefficient density is spread over the whole vacuum calculations as well as the polarizable continuum
scaffold (Figure 16).
model (PCM) with dichloromethane as a solvent [70] (for
details on the DFT calculations, see Supporting Information
File 1). The optimized geometries were verified by frequency
Computational studies on α-pyrones 6
For further elucidation of the electronic structure the geome- analyses of the local minima. The electronic absorptions of the
tries of the electronical ground-state structures of the α-pyrones α-pyrones 6 were calculated on the level of TDDFT theory em-
Figure 16: Selected DFT-computed (B3LYP 6-311G**) Kohn–Sham FMOs for 1H-pyridines 5f and 5g representing contributions of the longest wave-
length Franck–Condon absorption bands.
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Beilstein J. Org. Chem. 2019, 15, 2684–2703.
ploying the B3LYP functional and the Pople 6-311G** basis tion of α-pyrones. The strongly electron-donating p-N,N-
set. The calculated absorption maxima are in accordance with dimethylaminophenyl group furnishes α-pyrones.
the experimentally determined maxima (for details, see
Table S10 in Supporting Information File 1). For all α-pyrones 1H-Pyridines absorb and emit intensively in solution and in the
6 the longest wavelength maxima are characterized by solid state. While the absorption behavior is not affected by the
Franck–Condon S1 states representing HOMO–LUMO transi- substitution pattern the emission maxima are shifted
tions (Figure 17).
bathochromically with increasing acceptor strength. The same
trend manifests for the solid-state emission.
The computed Kohn–Sham frontier molecular orbitals show
that the coefficient density of the HOMO in the parent α-pyrone For α-pyrones the photophysical properties are considerably
6a is localized on the α-pyrone core and on the phenyl substitu- depending on the substituent pattern. The absorption and emis-
ent in the 6-position. For an N,N-dimethylaminophenyl substitu- sion maxima are shifted bathochromically with increasing
ent, there is no difference, but for an N,N-dimethylamino- donor strength. α-Pyrones are only weakly fluorescent in solu-
phenyl substituent in the 4-position the coefficient density is tion. However, with distinct p-N,N-dimethylaminophenyl sub-
shifted towards this substituent. With electron-donating substit- stitution in 6-position, an extraordinarily high fluorescence
uents in the 4- and 6-position, the coefficient density is again quantum yield of 99% in solution and 11% in the solid state
located on the core and the phenyl substituent in 6-position. was achieved. Interestingly, the isomeric p-N,N-dimethylamino-
Donor substituents in 4-position and acceptor substituents in phenyl substitution in 6-position represents a system with
6-position cause a coefficient density shift towards the 4-sub- aggregation-induced emission enhancement. These design prin-
stituent. The coefficient density in the LUMO in all compounds ciples of luminescent 1H-pyridines and α-pyrones as polarity
is spread over the whole scaffold.
sensitive tunable luminophores and the observed aggregation-
induced emission enhancement are currently under further in-
vestigation.
Conclusion
The cyclocondensation of alkynones and ethyl cyanoacetate,
depending on the reaction conditions, the type of base, and the
reaction temperature, as well as the electronic nature of the
alkynone 3 furnishes either 1H-pyridines or α-pyrones. Opti-
mized reaction conditions finally give rise to 8 examples of
1H-pyridines and 6 examples of α-pyrones. While the presence
of electron-withdrawing substituents mainly furnish
1H-pyridines and electron-donating groups lead to the forma-
Experimental
Typical procedure for the cyclocondensation
synthesis of compound 5d
1-Phenyl-3-[4-(trifluoromethyl)phenyl]prop-2-yn-1-one (3h,
1.40 g, 5.00 mmol), was placed in a dry Schlenk tube and
ethanol (10 mL) was added. Sodium carbonate (430 mg,
4.00 mmol), sodium acetate (250 mg, 3.00 mmol), water
Figure 17: Selected DFT-computed (B3LYP 6-311G**) Kohn–Sham FMOs for 1H-pyridines 6a, 6c, 6e, 6f, and 6g and representing contributions of
the longest wavelength Franck-Condon absorption bands.
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Beilstein J. Org. Chem. 2019, 15, 2684–2703.
(5 mL), and ethyl cyanoacetate (4, 2.31 g, 20.0 mmol) were 7.51–7.58 (m, 3H), 7.67–7.73 (m, 2H), 7.78–7.85 (m, 2 H);
added and the mixture was stirred at 75 °C for 16 h. After the 13C NMR (75 MHz, CDCl3) δ 40.2 (CH3), 91.1 (Cquat), 100.1
addition of CH2Cl2 (5.00 mL) and NaOH/FeSO4 solution (CH), 111.8 (CH), 115.7 (Cquat), 116.5 (Cquat), 128.0 (CH),
(5.00 mL), the solution was extracted with CH2Cl2 128.8 (CH), 129.3 (CH), 131.6 (CH), 135.3 (Cquat), 153.4
(3 × 50.0 mL). The combined organic layers were dried (an- (Cquat), 160.3 (Cquat), 164.1 (Cquat), 164.9 (Cquat). EIMS
hydrous MgSO4) and the solvent was removed in vacuo. The (70 eV, m/z (%)): 317 (15), 316 ([M]+, 66), 293 (11), 289 ([M −
residue was purified by flash chromatography on silica gel CN]+, 11), 288 ([M − CO]+, 51), 287 (19), 167 ([M −
(n-hexane/EtOAc 12:1 to 5:1 to 0:1) and washed with hot C9H11NO]+, 18), 150 (11), 149 ([M − C11H5NO]+, 100), 148
ethanol (5 mL) to give compound 5d (513 mg, 25%) as orange (20), 144 (13), 127 ([M − C11H11NO2]+, 12), 85 (13), 71 (22),
solid. Mp 223–233 °C; 1H NMR (300 MHz, CDCl3) δ 1.38 (t, 57 (18), 43 ([M − C18H11NO2]+, 13); IR (ATR) ν̃ [cm−1]: 3092
J = 7.1 Hz, 3H), 4.30 (q, J = 7.1 Hz, 2H), 7.12 (dd, J = 1.5, (w), 3048 (w), 2901 (w), 2864 (w), 2812 (w), 2739 (w), 2212
1.6 Hz, 1H), 7.44 (dd, J = 1.5, 1.6 Hz, 1H), 7.56–7.63 (m, 3H), (w), 1708 (m), 1706 (m), 1609 (m), 1589 (m), 1570 (m), 1530
7.78–7.84 (m, 6H), 14.57 (s, 1H); 13C NMR (150 MHz, CDCl3) (m), 1497 (m), 1491 (m), 1482 (m), 1478 (m), 1473 (m), 1467
δ 14.7 (CH3), 60.6 (CH2), 63.5 (Cquat), 109.2 (CH), 116.0 (CH), (m), 1458 (m), 1433 (m), 1375 (m), 1360 (m), 1333 (m), 1252
119.5 (Cquat), 123.9 (q, JC–F = 273 Hz, Cquat), 126.1 (CH), (m), 1209 (m), 1171 (m), 1159 (m), 1125 (m), 1111 (m), 1082
126.2–126.7 (m, CH), 127.8 (CH), 130.1 (CH), 131.6 (CH), (m), 1059 (m), 1020 (m), 995 (m), 953 (m), 945 (m), 924 (w),
132.3 (Cquat), 132.4 (q, JC–F = 32.9 Hz, Cquat), 140.6 (Cquat), 853 (m), 818 (s), 795 (m), 750 (m), 748 (m), 692 (s), 669 (m),
146.6 (Cquat), 151.2 (Cquat), 156.0 (Cquat), 171.0 (Cquat); EIMS 640 (m); UV–vis (CH2Cl2) λmax [nm] (ε [L·mol−1·cm−1]): 294
(70 eV, m/z (%)): 410 ([M]+, 24), 366 (24), 365 ([M − (18800), 482 (47300); emission (CH2Cl2) λmax [nm] (Stokes-
C2H5O]+, 100), 339 (12), 338 ([M − C3H5O2]+, 53), 337 (38), shift [cm−1]): 567 (3100); quantum yield (CH2Cl2) Φf: 0.99;
308 (8), 240 (23), 149 ([M − C16H12F3]+, 11); IR (ATR) ν
̃
emission (solid) λmax [nm]: 694; quantum yield (solid) Φf: 0.11;
[cm−1]: 3092 (w), 2992 (w), 2963 (w), 2943 (w), 2876 (w), Anal. calcd for C20H16N2O2 (316.1): C, 75.93; H, 5.10; N,
2806 (w), 2193 (m), 1625 (m), 1620 (m), 1597 (m), 1577 (m), 8.86; found: C, 75.74; H, 5.19; N, 8.56.
1506 (w), 1466 (w), 1413 (w), 1396 (w), 1369 (w), 1308 (m),
Typical procedure for the cyclocondensation
1300 (m), 1283 (s), 1258 (m), 1206 (w), 1165 (m), 1115 (s),
1092 (m), 1082 (m), 1071 (m), 1045 (s), 1030 (m), 1015 (m), synthesis of compound 8a
980 (m), 976 (m), 968 (w), 920 (w), 885 (w), 874 (w), 837 (s), 1,3-Diphenylprop-2-yn-1-one (3a, 103 mg, 0.50 mmol) was
829 (m), 764 (s), 745 (w), 727 (w), 685 (m), 662 (w), 655 (w), placed in a dry Schlenk tube and ethanol (1.00 mL) was added.
650 (w); UV–vis (CH2Cl2) λmax [nm] (ε [L·mol−1·cm−1]): 274 Sodium carbonate (43.0 mg, 0.40 mmol), sodium acetate
(32000), 321 (18100), 428 (10000); emission (CH2Cl2) λmax (25.0 mg, 0.30 mmol), water (50.0 µL) and diethyl (Z)-3-
[nm] (Stokes shift [cm−1]): 565 (5700); quantum yield amino-2-cyanopent-2-endioate (7, 226 mg, 1.00 mmol) were
(CH2Cl2) Φf: 0.01; Anal. calcd for C23H17F3N2O2 (410.1): C, added and the mixture was stirred at 75 °C for 16 h. After the
67.31; H, 4.18; N, 6.83; found: C, 67.50; H, 4.32; N, 6.70.
addition of CH2Cl2 (5.00 mL) and NaOH/FeSO4 solution
(5.00 mL), the solution was extracted with CH2Cl2
(3 × 50.0 mL). The combined organic layers were dried (an-
hydrous MgSO4) and the solvent was removed in vacuo. The
Typical procedure for the cyclocondensation
synthesis of compound 6c
1-[4-(Dimethylamino)phenyl]-3-phenylprop-2-yn-1-one (3c, residue was purified by flash chromatography on silica gel
249 mg, 1.00 mmol) was placed in a dry Schlenk tube and (n-hexane/EtOAc 5:1 to 1:1 to 0:1) and washed with hot ethanol
ethanol (2 mL) was added. Sodium carbonate (86.0 mg, (5.00 mL) to furnish compound 8a (108 mg, 52%) as yellow
0.80 mmol), sodium acetate (50.0 mg, 0.60 mmol), water solid. Mp 140–146 °C; 1H NMR (300 MHz, CDCl3) δ 1.08 (t,
(1 mL), and ethyl cyanoacetate (4, 462 mg, 4.00 mmol) were J = 7.2 Hz, 3H), 1.37 (t, J = 7.1 Hz, 3H), 4.22 (q, J = 7.2 Hz,
added and the mixture was stirred at 75 °C for 16 h. After the 2H), 4.31 (q, J = 7.1 Hz, 2H), 6.94 (d, J = 1.9 Hz, 1H),
addition of CH2Cl2 (5.00 mL) and NaOH/FeSO4 solution 7.40–7.48 (m, 5H), 7.55–7.62 (m, 3H), 7.75–7.84 (m, 2H),
(5.00 mL), the solution was extracted with CH2Cl2 15.60 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 13.7 (CH3), 14.7
(3 × 50.0 mL). The combined organic layers were dried (an- (CH3), 60.9 (CH2), 62.2 (CH2), 62.7 (Cquat), 112.2 (CH), 118.2
hydrous MgSO4) and the solvent was removed in vacuo. The (Cquat), 122.8 (Cquat), 126.3 (CH), 127.9 (CH), 128.8 (CH),
residue was purified by flash chromatography on silica gel 129.6 (CH), 130.1 (CH), 131.77 (CH), 131.84 (Cquat), 137.4
(n-hexane/EtOAc 5:1 to 1:1 to 0:1) and washed with hot ethanol (Cquat), 146.1 (Cquat), 151.9 (Cquat), 153.0 (Cquat), 165.1
(2.00 mL) and compound 6c (37.0 mg, 12%) was obtained as (Cquat), 172.1 (Cquat); EIMS (70 eV, m/z (%)): 415 ([M + H]+,
deep purple solid. Mp 224–253 °C; 1H NMR (300 MHz, 26), 414 ([M]+, 97), 369 ([M − C2H5O]+, 18), 342 (28), 341
CDCl3) δ 3.10 (s, 6H), 6.69 (s, 1H), 6.69–6.75 (m, 2H), ([M − C3H5O]+, 27), 340 ([M − C3H6O]+, 12), 314 (20), 313
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Beilstein J. Org. Chem. 2019, 15, 2684–2703.
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IR (ATR) ν̃ [cm−1]: 2978 (w), 2895 (w), 2197 (m), 1722 (m),
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Acknowledgements
The authors gratefully acknowledge the Deutsche Forschungs-
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The reported results have been summarized in the inaugural
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