Synthesis of Benzoacridines and Benzophenanthridines by Regioselective Pd-Catalyzed Cross-Coupling Reactions Followed by Acid-Mediated Cycloisomerizations

Article abstract of DOI:10.1002/ejoc.201900913

A convenient synthesis of various benzoacridines and benzophenanthridines from readily available dihalogenated quinolines is reported. The synthesis is based on regioselective Suzuki and Sonogashira reactions followed by Br?nsted acid-mediated cycloisomerization. The developed methodology is highly modular and allows the construction of various ring systems and substitution patterns in high yields. The optical and electrochemical properties of selected derivatives were investigated.

Full text of DOI:10.1002/ejoc.201900913

A Journal of
Accepted Article
Title: Synthesis of benzoacridines and benzophenanthridines by
regioselective Pd catalyzed cross-couplings followed by acid
mediated cycloisomerizations
Authors: Sophie Janke, Sebastian Boldt, Karapet Ghazargan, Peter
Ehlers, Peter Langer, and Alexander Villinger
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201900913
Link to VoR: http://dx.doi.org/10.1002/ejoc.201900913
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European Journal of Organic Chemistry
10.1002/ejoc.201900913
1
Synthesis of benzoacridines and benzophenanthridines by
regioselective Pd catalyzed cross-couplings followed by acid
mediated cycloisomerizations
a
a
b
a,c
Sophie Janke, Sebastian Boldt, Karapet Ghazargan, Dr. Peter Ehlers, Dr. Alexander
a
a,c
Villinger, Prof. Dr. Peter Langer,*
a
Institute of Chemistry, University Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany.
E-mail: peter.langer@uni-rostock.de; Fax: +49 381 498 6412; Tel: +49 381 498 6410; Web:
www.langer.chemie.uni-rostock.de
b
Institute of Chemistry, Yerevan State University, 1 Alek Manukyan St, Yerevan 0025, Armenia.
c
Leibniz Institute for Catalysis at the University of Rostock e.V. (LIKAT), Albert-Einstein-Str. 29a, 18059
Rostock, Germany.
Abstract. A convenient synthesis of various benzoacridines and benzophenanthridines from
readily available dihalogenated quinolines is reported. The synthesis is based on
regioselective Suzuki- and Sonogashira reactions followed by Brønsted acid mediated
cycloisomerization. The developed methodology is highly modular and allows the
construction of various ring systems and substitution patterns in high yields. The optical and
electrochemical properties of selected derivatives were investigated.
Keywords: cyclization; catalysis; palladium; heterocycles; regioselectivity
Graphical Abstract
Key Topic: Cycloisomerisation
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European Journal of Organic Chemistry
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TOC Text:
Various Benzoacridines and Benzophenanthridines have been synthesized by Brønsted acid
mediated cycloisomerisation as the key step. The optical and and electrochemical properties
have been studied by UV/Vis- and emission spectroscopy as well as CV measurements.
Obtained results have been verified by DFT calculations.
Introduction
Polyaromatic N-heterocycles, such as acridines, phenanthridines and related compounds, have
[
1],[2]
attracted considerable interest, because of their broad range of properties
. They constitute
well-known classes of biologically active compounds with pharmacological effects, including
[3]
antibacterial, antimalarial and anticancer activities. There action is often based on DNA and
[
4]
[5,6]
[7]
RNA intercalating. Proflavine (a Rev inhibitor),
aminacrine (antibacterial activity) ,
[
7]
[8]
and ethacridine (antibacterial activity) as well as NK109 (antitumor activity) , Ethidium
[
6]
[9]
(
antitumor activity) and Fagaronine (antileukemic activity) represent pharmacologically
significant acridines or phenanthridines (Figure 1). Furthermore, such substances have been
applied in industry as pigments or dyes and are expected to be promising candidates for the
[
10–12]
development of organic semiconductors.
Figure 1. Pharmacologically important acridines and phenanthridines
In this regard, many studies have been focused on the development of efficient synthetic
methodologies for the synthesis of such compounds. Reported synthetic strategies mainly rely
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European Journal of Organic Chemistry
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3
[
13,10–12]
[14]
[15]
on C–H functionalizations,
reductions,
dehydrations,
intermolecular
[
16]
[17]
[18]
annulations,
intramolecular cyclizations
and other methods . However, the
applicability of those methods is often limited with regard to the preparative scope. As part of
[19]
our ongoing interest in chemoselective Pd-catalyzed reactions of quinolines
and
[20]
cycloisomerization reactions, we herein wish to report a new and convenient synthesis of
benzoacridine and benzophenanthridine derivatives starting from dihalogenated quinolines
(Scheme 1).
Scheme 1. Synthesis of benzoacridine and benzophenanthridine derivatives
Results and Discussion
The starting materials, 3-bromo-2-iodoquinoline (1) and 4-bromo-3-iodoquinolines 8a,b, were
[
21]
prepared according to previously reported procedures (Scheme 1).
Subsequently,
chemoselective Suzuki reactions of 1 with various arylboronic acids were carried out,
followed by Sonogashira reaction in position 3 (Scheme 2). Due to the better leaving group
ability of iodide as compared to bromide, the Suzuki reaction of 1 proceeds chemoselectively
at the carbon-iodine bond to give 2-aryl-3-bromoquinolines 2a-f in 65-77% yield. During the
optimization, the use of Pd(dppf)Cl as the catalyst (10 mol%) and Cs CO as the base and the
2
2
3
temperature (60 °C) proved to be important parameters to avoid double coupling reactions
and to get the desired products in good yields. The Sonogashira reaction of 2a-f with various
alkynes afforded 2-aryl-3-alkynylquinolines 3a-o in 64-96% yields. The highest yield was
observed for 3m, while the lowest occurred with 64% for 3l.
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European Journal of Organic Chemistry
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Scheme 2. Synthesis of coupling products 2a-f and 3a-o
The Brønsted acid mediated cycloisomerization of 3a was studied next using different
sulfonic acids (Table 1). p-Toluenesulfonic acid (pTSA) and methanesulfonic acid (MSA)
performed equally well and gave the final product 4a in quantitative yields. During the
optimization it became apparent that “solvent-free” conditions are superior as compared to the
employment of xylene as solvent. The use of MSA allowed to decrease the amount of acid to
3
0 equivalents. Further reduction of the amount of acid resulted in low conversion, due to
poor solubility of the employed reagents.
Table 1. Optimization for the cyclization reaction of 3a
[
a]
Entry
Sulfonic acid
pTSA
Solvent
Equivalents
Yield
1
2
3
4
xylene
60
60
60
60
30
79%
98%
67%
99%
pTSA
--
--
--
--
Triflic acid
MSA
5
MSA
99%
[
a]
Isolated yields
With the optimized conditions in hand, the scope was studied and cyclization reactions of
compounds 3a-o were carried out (Table 2). Electron-poor and electron-rich systems gave
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European Journal of Organic Chemistry
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equally good results independently from the substitution pattern of the alkynyl groups (4b-d)
and aryl groups (4i-k). Slightly deviating results were observed for 4m and 4n, due to the
presence of the electron withdrawing fluorine substituent, deactivating the aryl ring for
electrophilic substitution. Heterocyclic product 4h, containing a thiophene moiety, could also
be prepared, albeit, in only 30% yield. The low yield can be explained by purification
problems during column chromatography. Methoxy groups were cleaved under the reaction
conditions to give the corresponding phenol derivatives in high yields. Benzoacridine 4j was,
as expected, obtained as a mixture of isomers in a ratio of 10:6.5 in favor of the less sterically
hindered derivative 4j (Figure 2).
1
1
Figure 2. Isomeric ratio of compound 4j as determined by H-NMR of the isomeric mixture
after purification
[
a]
Table 2. Synthesis of benzo[c]acridines 4a-o
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European Journal of Organic Chemistry
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[
a]
Isolated yields. * Mixture of regioisomers (10:6.5).
The molecular structure of benzo[c]acridine 4n was independently confirmed by X-ray crystal
structure analysis (Figure 3). It forms layers in a triclinic crystal lattice. The aromatic 3-
fluorobenzoacridine core is planar with the p-tolyl ring twisted out of plane by 54.5°.
[
22]
Figure 3. ORTEP of compound 4n (propability of ellipsoids: 50%)
With a series of benzo[c]acridines 4a-o being prepared, we turned our attention to the
synthesis of regioisomeric benzo[a]acridines, benzo[i]phenanthridines and
benzo[k]phenanthridines. This required the synthesis of the corresponding
alkynylarylquinolines as cyclization precursors. During the optimization of the conditions of
the synthesis of these starting materials, the first coupling reaction of the dihalogenated
quinoline played a crucial role to avoid double couplings.
The Sonogashira reaction of 1 with phenylacetylene in the presence of Pd(PPh ) (5 mol%) at
3
4
2
0 °C afforded the desired 2-aryl-3-bromoquinoline 5a in 80% yield (Table 3). 2,3-
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European Journal of Organic Chemistry
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Dibromoquinoline could not be used as the starting material, as both bromide atoms reacted
rapidly in the Sonogashira reaction. Although position 2 is more electron poor than position 3,
this difference is oviously not strong enough to guarantee a high degree of regioselectivity.
This can be explained by the fact that the reactivity of the system is increased after the first
coupling steps. This effect has been earlier observed for Sonogashira reactions of
[
23]
pentachloropyridine.
The temperature also played an important role. At elevated
temperature (80 °C) no product could be isolated, because of formation of significant amounts
of product derived from double coupling.
Table 3. Optimization for the Sonogashira reaction of 1
[
a]
Entry
Temperature
Time
24 h
2 h
Yield
0%
1
80 °C
2
rt
94%
[
a]
Isolated yields
The Suzuki reaction of 8a with phenylboronic acid afforded 3-aryl-4-bromoquinoline 9a in up
to 65% yield. During the optimization, the solvent (DMF/water) played an important role
(Table 4).
Table 4. Optimization for the Suzuki reaction of 8a
[
a]
Entry
Catalyst
Base
Solvent
Equivalents
Yield
(boronic acid)
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European Journal of Organic Chemistry
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1
2
Pd(dppf)Cl2
Pd(PPh3)4
Cs CO
THF
1.2
1.2
48%
59%
2
3
Na CO3
DMF/water
2
(
10:1)
DMF/water
10:1)
3
Pd(PPh3)4
Na CO3
1
65%
2
(
[
a]
Isolated yields
The Sonogashira reaction of 8a with phenylacetylene in the presence of Pd(PPh ) (5 mol%)
3
4
at 25 °C afforded the desired 3-alkynyl-4-bromoquinoline 12a in 68% yield (Table 5).
Besides the choice of the catalyst, the solvent (NEt /MeCN) and the temperature (25 °C)
3
played an important role to avoid Sonogashira reaction at position 4 and also nucleophilic
attack at the highly activated position 2.
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European Journal of Organic Chemistry
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Table 5. Optimization for the Sonogashira reaction of 8a
[
a]
Entry
Catalyst
Solvent
NEt3
Temperature
25 °C
Yield
1
Pd(PPh ) Cl
46%
56%
3
2
2
2
Pd(PPh ) Cl
NEt3
80 °C
3
2
2
3
Pd(PPh3)4
NEt /MeCN
25 °C
68%
3
[
a]
Isolated yields
The required starting materials were synthesized as shown in Scheme 3 (for synthetic details
see SI). The Sonogashira and subsequent Suzuki reaction of 3-bromo-2-iodoquinoline (1)
afforded 2-alkynyl-3-arylquinolines 6a-d via 5a-d. The Suzuki and subsequent Sonogashira
reaction of 4-bromo-3-iodoquinolines 8a,b gave 3-aryl-4-alkynylquinolines 10a-d via 9a-d.
The Sonogashira and subsequent Suzuki reaction of 4-bromo-3-iodoquinolines 8a gave 3-
alkynyl-4-arylquinolines 13a-e via 12a-d.
Scheme 3. Synthesis of alkynylarylquinolines 6a-d, 10a-d and 13a-e; i, Sonogashira reaction,
ii, Suzuki reaction (for details, see experimental section)
The MSA mediated cycloisomerization of alkynylarylquinolines was next studied. The
cyclosomerization of 6a-d, 10a-d and 13a-e afforded benzo[a]acridines 7a-d,
benzo[i]phenanthridines 11a-d and benzo[k]phenanthridines 14a-e, respectively (Table 6).
The yields vary from moderate to excellent. The highest, nearly quantitative yields were
obtained for alkyl-substituted products 7b, 7c and 11d. Compound 11c, containing an
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European Journal of Organic Chemistry
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0
electron-withdrawing group, was obtained in a moderate yield of 53% which might be
explained by the fact that the acid mediated cycloisomerization via electrophilic aromatic
substitution naturally proceeds more slowly in case of electron poor systems. Heterocyclic
product 14e, containing a thiophene moiety, could be isolated in 30% yield. The relatively
low yield can be explained by purification problems during column chromatography.
[
a]
Table 6. Synthesis of cyclization products 7a-d, 11a-d and 14a-e
[
a]
Reaction conditions: MSA (30 equiv.), 120 °C, 24 h. Yields of isolated products
The comparison of benzoacridines and benzophenanthridines shows that both derivatives can
be synthesized in good to excellent yields by acid mediated cycloisomerization. The reaction
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European Journal of Organic Chemistry
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1
conditions slightly differ but electron-withdrawing and electron-donating groups both proved
to be compatible with the reactions and gave equally good yields. The yield of benzoacridine
and benzophenanthridine with a thiophene moiety is low but comparable to each other.
Physical properties
Absorption and emission spectra were measured for selected derivatives 4 and compared with
their regioisomeric analogues 7a, 11a and 14a. All derivatives of 4 show similar
optoelectronic properties. They show a strong absorption in the range of 280 nm to 300 nm,
followed by less intensive bands with a certain fine structure up to 390 nm, typical for
[24]
benzoacridine derivatives.
The excitation energy for emission was about 360 nm for
compounds 4 and 7 and approximately 340 nm for 11 and 14. For all studied derivatives of 4
an emission maximum was observed at approximately 400 nm, containing a shoulder at
higher wavelengths (Figure 4). Fluorescence quantum yields are in the range of 20−43%
(Table 7 and SI). Intersection of the normalized absorption and emission spectra were used to
determine the optical band gaps [E(0-0)] ranging from 3.14 eV to 3.20 eV (Table 7 and SI). In
comparison to 4a, acridine 7a, exhibiting a different annulation system, shows only little
differences with regard to the optical properties (Figure 5). In contrast, the absorbtion and
emission bands of phenanthridines 11a and 14a are hypsochromically shifted with regard to
4
1
3
a, with 11a showing a stronger blue shift than 14a. The quantum yield decreases to 13% for
1a and 16% for 14a (Figure 5, Table 7 and SI). The optical band gap [E(0-0)] ranges from
.29 eV for 11a to 3.50 eV for 14a (Table 7 and SI) and, thus, are slightly increased as
compared to acridines 4 and 7.
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European Journal of Organic Chemistry
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2
Figure 4. Absorption and emission spectra for 4a (black), 4b (red), 4g (blue), 4h (magenta),
i (green), 4l (dark blue), 4m (purple)
4
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European Journal of Organic Chemistry
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Figure 5. Absorption and emission spectra for 4a (blue), 7a (green), 11a (black), 14a (red)
Table 7. Optical data
Property
4a
4b
4g
4h
4i
4l
4m
7a
11a
14a
279
2
82
282
281
282
284
295
283
283
271
λabs1[nm]
a
(5.7) (4.6) (6.4) (4.1) (5.8) (6.0) (4.9) (4.4) (6.2) (3.4)
(
ε )
1
2
92
292
292
292
293
340
288
290
329
318
λabs2 [nm]
a
(5.9) (4.9) (6.2) (4.3) (6.0) (0.6) (4.9) (4.6) (1.2) (1.1)
(
ε )
2
3
24
324
338
324
339
355
296
338
361
(0.3)
λabs3 [nm]
a
(0.6) (0.6) (0.7) (0.5) (0.6) (0.7) (4.6) (0.6)
(
ε )
3
3
38
339
353
340
353
373
334
352
380
(0.3)
λabs4 [nm]
a
(0.7) (0.6) (0.6) (0.6) (0.6) (0.9) (0.6) (0.6)
(
ε )
4
3
53
354
371
354
372
394
349
370
λabs5 [nm]
a
(0.6) (0.5) (0.8) (0.5) (0.9) (1.0) (0.7) (0.8)
(
ε )
5
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European Journal of Organic Chemistry
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4
3
72
373
391
372
393
367
(0.9) (0.9)
390
λabs6 [nm]
a
(0.8) (0.7) (0.8) (0.6) (0.9)
(
ε )
6
3
92
393
393
(0.6)
387
(0.9)
λabs7 [nm]
a
(0.8) (0.7)
(
ε )
7
[
b]
[b]
[b]
[b]
[b]
[b]
4
07
415
408
418 407
409
400 404
367
394
410
16
λem1 [nm]
λem2 [nm]
[
b]
4
16
26
3.20
385
2
1
26
23
20
28
3.16
43
37
13
ϕ [%]
E(
0-0)
3.16
3.14
3.17
3.14
3.15
3.18 3.29 3.50
[
c]
[
eV]
[
a]
-4
-1
-1 [b]
[c]
[
10 Lmol cm ]. contains a shoulder. Measured in dichloromethane and determined
via intersection of the normalized absorption and emission spectrum
Cyclic voltammetry measurements were performed for selected derivatives 7a and 11a in
CH Cl using 0.1M Bu NPF as the electrolyte, a glassy carbon working electrode, ANE2 as
2
2
4
6
the reference electrode, and a Pt counter-electrode with ferrocene as the standard (Figure 6).
+
S /S
The oxidation potentials (E( ) vary between 0.39 V and 0.40 V as well as 0.87 V and 0.99 V
-
and the reduction potentials E(S/S ) between -1.31 V and -1.34 V versus NHE (Table 8). In
comparison, benzophenanthridine 11a shows a higher oxidation potential and lower reduction
potential than benzoacridine 7a.
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European Journal of Organic Chemistry
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5
Figure 6: Cyclic Voltammetry measured in CH Cl , 0.1M Bu NPF , glassy carbon working
2
2
4
6
electrode, ANE2 as reference electrode, and Pt counter electrode with ferrocene as standard.
Red 11a, black 7a
Table 8: Electrochemical data of 4a, 7a, 11a and 14a
Property
4a
7a
11a
3.29
0.40
0.99
-1.34
-5.79
-6.08
-1.90
4.17
14a
[
a]
E(0-0) [eV]
3.16
3.18
0.39
0.87
-1.31
-5.67
-5.93
-2.15
3.77
3.50
+
[b]
[b]
E(
E(
[V]
[V]
S /S)1
+
S /S)2
-
[b]
E(
[V]
S/S )1
[
c]
EHOMO CV[eV]
-
[
d]
EHOMO Calc[eV]
-5.86
-2.14
3.72
-5.98
-1.91
4.07
[
d]
ELUMO Calc[eV]
[
d]
E(0-0) Calc [eV]
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European Journal of Organic Chemistry
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[
a]
Measured in dichloromethane and determined via intersection of the normalized absorption
[
b]
and emission spectrum.
Determined from the maximal oxidation potential. Measured in
CH Cl , 0.1M Bu NPF , glassy carbon working electrode, ANE2 as reference electrode and
2
2
4
6
[
c]
Pt counter-electrode with ferrocene as standard, given versus NHE. Determined from the
[
d]
onset oxidation potential. Computed and optimized with B3LYP at the 6-311G** Level
DFT calculations, using the B3LYP 6-311G(d,p) basis set, have been performed to verify the
[
25]
experimental results.
Visualization of the HOMO and LUMO orbitals are shown in
Table 9. For all studied compounds, the HOMOs and LUMOs are mainly located at the
benzoacridine or phenanthridine core structure, respectively. The aryl substituents are
expected not to significantly influence the electronic situation of the central core structure,
because they are twisted out of plane. The calculated data of the HOMO energies are slightly
lower as compared to the experimental data, whereby the HOMO energy of 7a decreases
from -5.67 eV (experimental value) to -5.93 eV (calculated value) and in case of 11a from
-5.79 eV (experimental value) to -6.08 eV (calculated value) (Table 9 and SI).
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European Journal of Organic Chemistry
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Table 9. Visualization of HOMO and LUMO orbitals of 4a, 7a, 11a and 14a from Y-Axis
HOMO orbitals
LUMO orbitals
4
a
4a
7
a
7
a
1
1a
1
1a
1
4a
14a
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European Journal of Organic Chemistry
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In conclusion, we developed a convenient synthetic pathway for the preparation of four
different series of benzoacridines and benzophenanthridines via cross-coupling reactions
followed by Brønsted acid mediated cycloisomerization. In all reactions, dihalogenated
quinolines were used as the starting materials. The different products could be accessed based
on location of the leaving groups in the quinoline system and based on the order of
Sonogashira and Suzuki reactions during the synthesis. The reactions are broadly applicable
and robust, various electron-withdrawing as well as electron-donating groups are tolerated
and the products were generally isolated in good to excellent yields. Selected products were
investigated by cyclic voltammetry as well as absorption and fluorescence spectroscopy.
These compounds show fluorescence with emission maxima around 390 nm and quantum
yields up to 43%. A slight difference between benzoacridines and benzophenanthridines was
observed regarding the HOMO-LUMO gap and the oxidation potential.
Experimental Section
General
If not otherwise indicated, chemicals used in this study were obtained from commercial
sources. No further purifications were done. Solvents, which were employed for work-up and
purification processes, were distilled according to standard procedures. Silica gel (particle
sizes 0.006 - 0.043 mm) were used for column chromatography.
Micro-Hot-Stage Galen TM III Cambridge Instrument was used for melting point
determination. The results were not further corrected.
NMR samples were measured with Bruker AVANCE 250 II (built 2006), Bruker AVANCE
3
0
7
00 III (built 2007) and AVANCE 500 (built
1). NMR-peaks were calibrated using standard peaks of chloroform (7.260 ppm for H and at
1
1
3
1
13
7.160 ppm for C) and dimethylsulfoxide (2.500 ppm for H and at 39.520 ppm for C).
For peak descriptions, following abbreviations were used: s (singlet), d (doublet), t (triplet),
dd (doublet doublet), td (triplet doublet), dt (doublet triplet), ddd (double doublet doublet).
IR measurement was performed with Bruker ALPHA-P spectrometer using ATR sampling
technique. W (weak), m (medium) and s (strong) were used for peak description.
GC/MS-measurements were conducted with Finnigan MAT 95-XP device using HP-5
capillary column with helium carrier gas and electron ionization (EI) scan technique at 70 eV.
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European Journal of Organic Chemistry
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For HRMS, Finnigan MAT 95 XP device was employed. Only signals with deviation of less
than ±2 mDa were accounted as correct.
X-Ray single crystal structure analysis was performed on a Bruker-Nonius Apex X8 CCD-
diffractometer.
UV−Vis spectra were recorded on an Agilent Cary 60 UV-Vis Spectrophotometer in 1 cm
cuvettes. Emission spectra were recorded on an Agilent Cary Eclipse Fluorescence
Spectrophotometer. Quantum yields were determined using quinine hemisulfate in 0.05 M
[
1]
H SO as fluorescence standard ( = 0.51 ). Cyclo voltammetric measurements were
2
4
performed on a Parstat 4000.
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European Journal of Organic Chemistry
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General synthetic procedures
3
-Bromo-2-iodoquinoline 1 and 4-bromo-3-iodoquinolines 8a-b were prepared according to
[
2]
previously reported procedures.
General procedure for the synthesis of 3-bromo-2-phenylquinolines 2a-f and 3-Phenyl-2-
phenylethynyl)quinolines 6a-d by Suzuki reaction
(
3
-Bromo-2-iodoquinoline 1 (0.6 mmol) or 3-bromo-2-(phenylethynyl)quinolines 5a-c
(
0.6 mmol), arylboronic acid (0.6 mmol), Pd(dppf)Cl (0.06 mmol) and Cs CO (1.2 mmol)
2
2
3
were subjected to a dried glass pressure tube. Afterwards, the tube was evacuated and
backfilled with argon three times. The solids were solved in 2.0 ml of dry THF, sealed with a
Teflon cap before being heated to 60 °C for 17 hours. After the reaction was completed
(monitored by TLC), it was allowed to cool to room temperature. The residue was dissolved
in CH Cl (20.0 ml), washed with water (20.0 ml) and dried over Na SO . The crude oil was
2
2
2
4
purified by column chromatography (heptane/ethyl acetate 40:1).
General procedure for the synthesis of 2-phenyl-3-(phenylethynyl)quinolines 3a-o by
Sonogashira reaction
3
-Bromo-2-phenylquinolines 2a-f (0.7 mmol), alkyne (1.0 mmol), Pd(PPh ) Cl (0.035 mmol)
3 2 2
and CuI (0.07 mmol) were subjected to a dried glass pressure tube. Afterwards, the tube was
evacuated and backfilled with argon three times. The solids were solved in 6.0 ml of
triethylamine, sealed with a Teflon cap before being heated to 80 °C for 24 hours. After
2
4 hours, it was allowed to cool to room temperature. The residue was dissolved in CH Cl
2 2
(
20.0 ml), washed with water (20.0 ml) and dried over Na SO . The crude oil was purified by
2 4
column chromatography (heptane/ethyl acetate 20:1).
General procedure for the synthesis of 3-bromo-2-(phenylethynyl)quinolines 5a-c by
Sonogashira reaction
3
-Bromo-2-iodoquinoline 1 (0.8 mmol), alkyne (1.2 mmol), Pd(PPh ) Cl (0.04 mmol) and
3 2 2
CuI (0.08 mmol) were subjected to a dried glass pressure tube. Afterwards, the tube was
evacuated and backfilled with argon three times. The solids were solved in 3.0 ml of
triethylamine, sealed with a Teflon cap before being stirred at room temperature for 2 hours.
The residue was dissolved in CH Cl (20.0 ml), washed with water (20.0 ml) and dried over
2
2
Na SO . The crude oil was purified by column chromatography (heptane/ethyl acetate 20:1).
2
4
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European Journal of Organic Chemistry
10.1002/ejoc.201900913
2
1
General procedure for the synthesis of benzoacridines 4a-o and 7a-d
2
-Phenyl-3-(phenylethynyl)quinolines 3a-o or 3-phenyl-2-(phenylethynyl)quinolines 6a-d
(0.3 mmol), methanesulfonic acid (~0.65 ml) were added to a dried glass pressure tube. The
tube was evacuated and backfilled with argon three times. The mixture was heated to 120 °C
for 24 hours. After the reaction was completed (monitored by TLC), it was allowed to cool to
room temperature. The residue was dissolved in CH Cl (20.0 ml), washed with saturated
2
2
NaHCO (20.0 ml) and dried over Na SO . The crude oil was purified by column
3
2
4
chromatography (heptane/ethyl acetate 20:1).
General procedure for the synthesis of 4-bromo-3-(phenyl)quinolines 9a-d by Suzuki
reaction
4
-Bromo-3-iodoquinolines 8a-b (0.6 mmol), arylboronic acid (0.6 mmol), Pd(PPh3)4
(
0.03 mmol) and Na CO (1.2 mmol) were subjected to a dried glass pressure tube.
2
3
Afterwards, the tube was evacuated and backfilled with argon three times. The solids were
solved in 3.0 ml of DMF and 0.3 ml of water, sealed with a Teflon cap before being stirred at
1
00 °C for 24 hours. The residue was dissolved in CH Cl (20.0 ml), washed with water
2 2
(20.0 ml) and dried over Na SO . The crude product was purified by column chromatography
2 4
(heptane/ethyl acetate 10:1).
General procedure for the synthesis of 4-phenylethynyl-3-(phenyl)quinolines 10a-d by
Sonogashirareaction
4
-Bromo-3-phenylquinoline 9a-d (0.4 mmol), alkyne (0.6 mmol), Pd(PPh ) Cl (0.02 mmol)
3 2 2
and CuI (0.02 mmol) were subjected to a dried glass pressure tube. Afterwards, the tube was
evacuated and backfilled with argon three times. The solids were solved in 3.0 ml of
triethylamine, sealed with a Teflon cap before being stirred at 80 °C for 24 hours. The residue
was dissolved in CH Cl (20.0 ml), washed with water (20.0 ml) and dried over Na SO . The
2
2
2
4
crude product was purified by column chromatography (heptane/ethyl acetate 10:1).
General procedure for the synthesis of 4-bromo-3-(phenylethynyl)quinolines 12a-c by
Sonogashira reaction
4
-Bromo-3-iodoquinoline 8a (0.8 mmol), alkyne (1.3 mmol), Pd(PPh ) (0.04 mmol) and CuI
3 4
(0.04 mmol) were subjected to a dried glass pressure tube. Afterwards, the tube was evacuated
and backfilled with argon three times. The solids were solved in 1.0 ml of triethylamine and
2
ml of acetonitrile, sealed with a Teflon cap before being stirred at room temperature for
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201900913
2
2
2
4 hours. The residue was dissolved in CH Cl (20.0 ml), washed with water (20.0 ml) and
2 2
dried over Na SO . The crude product was purified by column chromatography (heptane/ethyl
2
4
acetate 10:1).
General procedure for the synthesis of 4-phenyl-3-(phenylethynyl)quinolines 13a-e by
Suzuki reaction
4
-Bromo-3-phenylethynylquinoline 12 (0.4 mmol), arylboronic acid (0.6 mmol), Pd(PPh3)4
(
0.02 mmol) and Na CO (0.8 mmol) were subjected to a dried glass pressure tube.
2
3
Afterwards, the tube was evacuated and backfilled with argon three times. The solids were
solved in 3.0 ml of DMF and 0.3 ml of water, sealed with a Teflon cap before being stirred at
1
00 °C for 24 hours. The residue was dissolved in CH Cl (20.0 ml), washed with water
2 2
(20.0 ml) and dried over Na SO . The crude product was purified by column chromatography
2 4
(heptane/ethyl acetate 10:1).
General procedure for the synthesis of benzophenanthridines 14a-e and 11a-d
3
-Phenyl-4-(phenylethynyl)quinolines 13a-e or 4-phenyl-3-(phenylethynyl)quinolines 10a-d
(~0.3 mmol), methanesulfonic acid (~0.65 ml) were added to a dried glass pressure tube. The
tube was evacuated and backfilled with argon three times. The mixture was heated to 120 °C
for 24 hours. After the reaction was completed (monitored by TLC), it was allowed to cool to
room temperature. The reaction was diluted with CH Cl (20.0 ml), washed with saturated
2
2
NaHCO (20.0 ml) and dried over Na SO . The crude product was purified by column
3
2
4
chromatography (heptane/ethyl acetate 5:1).
3
-Bromo-2-phenylquinoline 2a
-Bromo-2-iodoquinoline 1 (0.6 mmol), arylboronic acid (0.6 mmol), Pd(dppf)Cl2
3
(
0.06 mmol) and Cs CO (1.2 mmol) in 2.0 ml of dry THF gave 2a as white solid (125 mg,
2 3
1
7
4%), mp. 99 - 101 °C. H NMR (300 MHz, CDCl ) δ = 8.50 (s, 1H, CH ), 8.14 (d,
3 Ar
3
3
3
J = 8.5 Hz, 1H, CH ), 7.79 – 7.70 (m, 4H, CH ), 7.58 (ddd, J = 8.1 Hz, J = 7.0 Hz,
Ar
Ar
4
13
J = 1.2 Hz, 1H, CH ), 7.53 – 7.46 (m, 3H, CH ). C NMR (75 MHz, CDCl ) δ = 159.8
Ar
Ar
3
(
C ), 146.7 (C ), 140.1 (CH ), 140.0 (C ), 130.2 (CH ), 129.7 (CH ), 129.5 (2CH ),
Ar Ar Ar Ar Ar Ar Ar
1
29.0 (CH ), 128.3 (C ), 128.1 (2CH ), 127.5 (CH ), 126.6 (CH ), 117.0 (C ).
Ar Ar Ar Ar Ar Ar
-1
IR (ATR, cm ): ṽ = 3056 (w), 3049 (w), 2920 (w), 2850 (w), 1577 (m), 1480 (m), 1443 (m),
1
396 (m), 950 (m), 897 (m), 761 (m), 742 (s), 708 (m), 687 (s), 590 (m), 474 (m).
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European Journal of Organic Chemistry
10.1002/ejoc.201900913
2
3
+
+
MS (EI, 70 eV): m/z (%) = 285 ([M] , 15), 283 ([M] , 15), 205 (17), 204 (100), 203 (21), 202
(8), 177 (8), 176 (13), 102 (10), 101 (8), 75 (14), 51 (8). HRMS (EI): Calculated for
79
81
C H BrN 282.99911 found 282.9989, calculated for C H BrN 284.9971 found
15
10
15 10
2
84.99691.
3
-Bromo-2-(p-tolyl)quinoline 2b
3
-Bromo-2-iodoquinoline 1 (0.6 mmol), arylboronic acid (0.6 mmol), Pd(dppf)Cl2
(
0.06 mmol) and Cs CO (1.2 mmol) in 2.0 ml of dry THF gave 2b as pale yellow solid (127
2 3
1
mg, 71%), mp. 91 - 93 °C. H NMR (250 MHz, CDCl ) δ = 8.48 (s, 1H CH ), 8.14 (d,
3
,
Ar
3
3
J = 8.4 Hz, 1H CH ), 7.80 – 7.64 (m, 4H CH ), 7.56 (d, J = 7.5 Hz, 1H CH ), 7.32 (d,
,
Ar
,
Ar
,
Ar
3
13
J = 7.9 Hz, 2H, CH ), 2.45 (s, 3H, CH ). C NMR (63 MHz, CDCl ) δ = 158.3 (C ), 146.7
Ar
3
3
Ar
(
C ), 140.0 (CH ), 139.0 (C ), 137.2 (C ), 130.1 (CH ), 129.6 (CH ), 129.5 (2CH ),
Ar Ar Ar Ar Ar Ar Ar
1
28.8 (2CH ), 128.2 (C ), 127.4 (CH ), 126.5 (CH ), 117.1 (C ), 21.5 (CH ).
Ar Ar Ar Ar Ar 3
-1
IR (ATR, cm ): ṽ = 3055 (w), 2911 (w), 2852 (w), 1955 (w), 1928 (w), 1905 (w), 1795 (w),
581 (m), 1542 (m), 1482 (m), 1395 (m), 1067 (m), 950 (m), 893 (m), 881 (m), 819 (m), 779
m), 748 (s), 724 (m), 587 (m), 513 (m), 465 (m). MS (EI, 70 eV): m/z (%) = 300 (4), 299
1
(
(
+
+
[M] , 23), 297 ([M] , 23), 219 (18), 218 (100), 217 (25), 216 (13), 203 (9), 109 (13).
7
12
9
+
HRMS (ESI): Calculated for C H BrN [M+H] 298.0226 found 298.0228, calculated for
16
81
+
C H BrN [M+H] 300.0207 found 300.0208.
16
12
3
-Bromo-2-(m-tolyl)quinoline 2c
3
-Bromo-2-iodoquinoline 1 (0.6 mmol), arylboronic acid (0.6 mmol), Pd(dppf)Cl2
(
0.06 mmol) and Cs CO (1.2 mmol) in 2.0 ml of dry THF gave 2c as pale yellow solid (132
2 3
1
mg, 74%), mp. 61 - 63 °C. H NMR (300 MHz, CDCl ) δ = 8.49 (s, 1H, CH ), 8.19 – 8.10
3
Ar
3
3
4
(
m, 1H, CH ), 7.75 (ddd, J = 8.4 Hz, J = 7.2 Hz, J = 3.8 Hz, 2H, CH ), 7.61 – 7.51 (m,
A
r
A
r
3
3
H, CH ), 7.42 – 7.36 (m, 1H, CH ), 7.29 (d, J = 7.6 Hz, 1H, CH ), 2.46 (s, 3H, CH ).
Ar Ar Ar 3
1
3
C NMR (75 MHz, CDCl ) δ = 158.6 (C ), 146.7 (C ), 140.1 (CH ), 139.9 (C ), 138.0
3
Ar
Ar
Ar
Ar
(
C ), 130.2 (CH ), 130.1 (CH ), 129.8 (CH ), 129.7 (CH ), 128.4 (C ), 128.0 (CH ),
Ar Ar Ar Ar Ar Ar Ar
-1
1
27.5 (CH ), 126.7 (CH ), 126.6 (CH ), 117.2 (C ), 21.7 (CH ). IR (ATR, cm ): ṽ = 3055
Ar Ar Ar Ar 3
(w), 2919 (w), 1578 (m), 1543 (m), 1483 (m), 1446 (m), 1397 (m), 1385 (m), 1370 (m), 1272
(m), 1197 (m), 1082 (m), 1072 (m), 961 (m), 906 (m), 866 (m), 828 (m), 794 (m), 777 (m),
+
+
7
56 (s), 719 (m), 697 (m), 476 (m). MS (EI, 70 eV): m/z (%) = 299 ([M] , 19), 297 ([M] , 19),
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201900913
2
4
2
19 (18), 218 (100), 217 (28), 216 (13), 203 (7), 109 (12). HRMS (ESI): Calculated for
79
+
81
+
C H BrN [M+H] 298.0226 found 298.0226, calculated for C H12 BrN [M+H]
16
12
16
3
00.0207 found 300.0207.
3
-Bromo-2-(o-tolyl)quinoline 2d
3
-Bromo-2-iodoquinoline 1 (0.6 mmol), arylboronic acid (0.6 mmol), Pd(dppf)Cl2
(
0.06 mmol) and Cs CO (1.2 mmol) in 2.0 ml of dry THF gave 2d as white solid (138 mg,
2 3
1
7
7%), mp. 101 - 103 °C. H NMR (300 MHz, CDCl ) δ = 8.49 (s, 1H, CH ), 8.15 (dd,
3 Ar
3
4
3
J = 8.4 Hz, J = 0.6 Hz, 1H, CH ), 7.83 – 7.72 (m, 2H, CH ), 7.60 (ddd, J = 8.1 Hz,
Ar
Ar
3
4
13
J = 7.0 Hz, J = 1.1 Hz, 1H, CH ), 7.42 – 7.28 (m, 4H, CH ), 2.18 (s, 3H, CH ). C NMR
Ar
Ar
3
(
75 MHz, CDCl ) δ = 159.7 (C ), 146.6 (C ), 140.1 (C ), 139.2 (CH ), 135.9 (C ), 130.3
3 Ar Ar Ar Ar Ar
(
CH ), 130.1 (CH ), 129.6 (CH ), 128.9 (CH ), 128.7 (CH ), 128.5 (C ), 127.6 (CH ),
Ar Ar Ar Ar Ar Ar Ar
-
1
1
3
8
7
26.7 (CH ), 125.8 (CH ), 118.5 (C ), 19.6 (CH ). IR (ATR, cm ): ṽ = 3061 (w), 3047 (w),
Ar Ar Ar 3
018 (w), 2926 (w), 1484 (m), 1398 (m), 1370 (m), 1066 (m), 1038 (m), 954 (m), 906 (m),
+
70 (m), 784 (m), 760 (s), 728 (m), 595 (m), 472 (m). MS (EI, 70 eV): m/z (%) = 299 ([M] ,
+
), 297 ([M] , 7), 219 (17), 218 (100), 217 (46), 216 (21), 109 (16). HRMS (ESI): Calculated
7
12
9
+
81
+
for C H BrN [M+H] 298.0226 found 298.0227, calculated for C H BrN [M+H]
1
6
16 12
3
00.0207 found 300.0207.
3
-Bromo-2-(4-methoxyphenyl)quinoline 2e
3
-Bromo-2-iodoquinoline 1 (0.6 mmol), arylboronic acid (0.6 mmol), Pd(dppf)Cl2
(
0.06 mmol) and Cs CO (1.2 mmol) in 2.0 ml of dry THF gave 2e as yellow solid (141 mg,
2 3
1
7
5%), mp. 124 - 126 °C. H NMR (250 MHz, CDCl ) δ = 8.48 (s, 1H, CH ), 8.12 (dd,
3 Ar
3
4
J = 8.3 Hz, J = 0.7 Hz, 1H, CH ), 7.80 – 7.69 (m, 4H, CH ), 7.61 – 7.51 (m, 1H, CH ),
Ar
Ar
Ar
1
3
7
1
.08 – 6.95 (m, 2H, CH ), 3.88 (s, 3H, OCH ). C NMR (63 MHz, CDCl ) δ = 160.2 (C ),
Ar 3 3 Ar
57.7 (C ), 146.6 (C ), 140.0 (CH ), 132.3 (C ), 131.0 (2CH ), 130.0 (CH ), 129.4
Ar
Ar
Ar
Ar
Ar
Ar
(
CH ), 128.1 (C ), 127.2 (CH ), 126.4 (CH ), 117.1 (C ), 113.4 (2CH ), 55.4 (OCH ).
Ar Ar Ar Ar Ar Ar 3
-1
IR (ATR, cm ): ṽ = 3049 (w), 2934 (w), 2838 (w), 2048 (w), 1963 (w), 1607 (m), 1581 (m),
1
1
7
5
514 (m), 1481 (m), 1451 (m), 1396 (m), 1371 (m), 1302 (m), 1289 (m), 1248 (m), 1174 (m),
108 (m), 1070 (m), 1029 (m), 950 (m), 897 (m), 880 (m), 856 (m), 825 (s), 798 (m), 778 (m),
+
44 (s), 732 (m), 587 (m), 530 (m), 475 (m). MS (EI, 70 eV): m/z (%) = 316 (9), 315 ([M] ,
+
4), 314 (10), 313 ([M] , 53), 235 (19), 234 (100), 219 (28), 192 (8), 191 (55), 190 (36), 164
This article is protected by copyright. All rights reserved.

European Journal of Organic Chemistry
10.1002/ejoc.201900913
2
5
79
+
(
10), 163 (10), 96 (13), 75 (8). HRMS (ESI): Calculated for C H BrNO [M+H] 314.0175
16 12
81
+
found 314.0176, calculated for C H BrNO [M+H] 316.0156 found 316.0156.
1
6
12
3
-Bromo-2-(4-fluorophenyl)quinoline 2f
-Bromo-2-iodoquinoline 1 (0.6 mmol), arylboronic acid (0.6 mmol), Pd(dppf)Cl2
3
(
0.06 mmol) and Cs CO (1.2 mmol) in 2.0 ml of dry THF gave 2f as white solid (117 mg,
2 3
1
6
5%), mp. 142 - 144 °C. H NMR (250 MHz, CDCl ) δ = 8.50 (s, 1H, CH ), 8.12 (dd,
3 Ar
3
4
J = 8.3 Hz, J = 0.9 Hz, 1H ), 7.89 – 7.65 (m, 4H, CH ), 7.65 – 7.47 (m, 1H, CH ), 7.32 –
Ar
Ar
Ar
1
3
1
7
.06 (m, 2H, CH ). C NMR (75 MHz, CDCl ) δ = 163.2 (d, J = 248.6 Hz, CFAr), 157.1
Ar 3 CF
4
3
(
C ), 146.5 (C ), 140.1 (C ), 135.9 (d, J = 3.3 Hz, C ), 131.5 (d, J = 8.4 Hz, 2CHAr),
Ar Ar Ar CF Ar CF
1
30.2 (CH ) , 129.5 (CH ), 128.2 (CH ), 127.6 (CH ), 126.5 (CH ), 116.7 (C ), 115.1 (d,
Ar
Ar
Ar
Ar
Ar
Ar
2
19
-1
JCF = 21.7 Hz, 2CHAr). F NMR (282 MHz, CDCl ) δ = -112.38 (CF ). IR (ATR, cm ):
3
Ar
ṽ = 3056 (w), 2923 (w), 1598 (m), 1581 (m), 1510 (m), 1483 (m), 1394 (m), 1218 (m), 1162
(m), 1100 (m), 1069 (m), 953 (m), 900 (m), 881 (m), 835 (s), 780 (m), 747 (s), 729 (m), 587
+
+
(
m), 151 (m), 479 (m). MS (EI, 70 eV): m/z (%) = 303 ([M] , 24), 301 ([M] , 24), 223 (17),
7
9
+
2
3
22 (100), 221 (17), 194 (7), 111 (10). HRMS (ESI): Calculated for C H BrFN [M+H]
15 9
81
+
01.9975 found 301.9974, calculated for C H BrFN [M+H] 303.9956 found 303.9956.
1
6
12
2
-Phenyl-3-(phenylethynyl)quinoline 3a
-Bromo-2-phenylquinoline 2a (0.7 mmol), alkyne (1.0 mmol), Pd(PPh ) Cl (0.035 mmol)
3
3
2
2
and CuI (0.07 mmol) in 6.0 ml of triethylamine gave 3a as yellow solid (191 mg, 89%),
1
3
mp. 136 - 138 °C. H NMR (300 MHz, CDCl ) δ = 8.45 (s, 1H, CH ), 8.18 (dd, J = 8.4 Hz,
3
Ar
4
3
J = 0.6 Hz, 1H, CH ), 8.12 – 8.08 (m, 2H, CH ), 7.82 (d, J = 8.1 Hz, 1H, CH ), 7.74 (ddd,
Ar
Ar
Ar
3
3
4
J = 8.4 Hz, J = 6.9 Hz, J = 1.5 Hz, 1H, CH ), 7.61 – 7.49 (m, 4H, CH ), 7.46 – 7.38 (m,
Ar
Ar
1
3
2
H, CH ), 7.37 – 7.30 (m, 3H, CH ). C NMR (75 MHz, CDCl ) δ = 159.4 (C ), 147.0
Ar Ar 3 Ar
(
C ), 140.6 (CH ), 139.8 (C ), 131.5 (2CH ), 130.4 (CH ), 129.7 (2CH ), 129.7 (CH ),
Ar Ar Ar Ar Ar Ar Ar
1
1
29.1 (CH ), 128.7 (CH ), 128.5 (2CH ), 128.0 (2CH ), 127.2 (CH ), 127.1 (CH ),
Ar Ar Ar Ar Ar Ar
-1
26.4 (C ), 123.0 (C ), 116.3 (C ), 94.7 (CAlkyne), 88.1 (CAlkyne). IR (ATR, cm ): ṽ = 3056
Ar
Ar
Ar
(w), 3030 (w), 2923 (w), 2212 (w), 1596 (w), 1570 (w), 1479 (m), 1442 (m), 1413 (m), 1368
(m), 911 (m), 769 (m), 750 (s), 718 (m), 695 (m), 686 (s), 533 (m), 477 (m). MS (EI, 70 eV):
+
m/z (%) = 306 (11), 305 ([M] , 58), 304 (100), 303 (21), 302 (13), 301 (7), 200 (7), 152 (9),
+
1
51 (8). HRMS (ESI): Calculated for C H N [M+H] 306.1277 found 306.1273.
2
3
15
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European Journal of Organic Chemistry
10.1002/ejoc.201900913
2
6
2
-Phenyl-3-(p-tolylethynyl)quinoline 3b
-Bromo-2-phenylquinoline 2a (0.7 mmol), alkyne (1.0 mmol), Pd(PPh ) Cl (0.035 mmol)
3
3
2
2
and CuI (0.07 mmol) in 6.0 ml of triethylamine gave 3b as yellow solid (204 mg, 91%),
1
3
mp. 143 - 145 °C. H NMR (300 MHz, CDCl ) δ = 8.43 (s, 1H, CH ), 8.16 (d, J = 9.1 Hz,
3
Ar
3
4
1
H, CH ), 8.11 – 8.06 (m, 2H, CH ), 7.82 (dd, J = 8.1 Hz, J = 1.2 Hz, 1H, CH ), 7.73
Ar Ar Ar
3
3
4
(
ddd, J = 8.4 Hz, J = 6.9 Hz, J = 1.5 Hz, 1H, CH ), 7.59 – 7.48 (m, 4H, CH ), 7.33 – 7.28
Ar Ar
3
13
(
m, 2H, CH ), 7.14 (d, J = 7.9 Hz, 2H, CH ), 2.36 (s, 3H, CH ). C NMR (75 MHz,
Ar
Ar
3
CDCl ) δ = 159.9 (C ), 147.4 (C ), 140.9 (CH ), 140.3 (C ), 139.4 (C ), 131.9 (2CH ),
3
Ar
Ar
Ar
Ar
Ar
Ar
1
1
30.8 (CH ), 130.2 (2CH ), 130.1 (CH ), 129.7 (2CH ), 129.5 (CH ), 128.5 (2CH ),
Ar Ar Ar Ar Ar Ar
27.6 (CH ), 127.5 (CH ), 126.9 (C ), 120.4 (C ), 117.0 (C ), 95.4 (CAlkyne), 87.9
Ar
Ar
Ar
Ar
Ar
-1
(
CAlkyne), 22.1 (CH ). IR (ATR, cm ): ṽ = 3056 (w), 3039 (w), 3024 (w), 2912 (w), 2851 (w),
3
2
9
211 (w), 1585 (w), 1554 (w), 1509 (m), 1479 (m), 1411 (m), 1367 (m), 1182 (m), 953 (m),
13 (m), 816 (m), 768 (m), 750 (s), 719 (m), 696 (s), 534 (m). MS (EI, 70 eV): m/z (%) = 320
+
(
(
[
19), 319 ([M] , 88), 318 (100), 317 (12), 316 (16), 315 (9), 305 (9), 304 (39), 303 (25), 302
11), 301 (6), 213 (7), 158 (14), 152 (11), 151 (7). HRMS (ESI): Calculated for C H N
2
4
17
+
M+H] 320.1434 found 320.1428.
2
-Phenyl-3-(m-tolylethynyl)quinoline 3c
-Bromo-2-phenylquinoline 2a (0.7 mmol), alkyne (1.0 mmol), Pd(PPh ) Cl (0.035 mmol)
3
3
2
2
and CuI (0.07 mmol) in 6.0 ml of triethylamine gave 3c as yellow solid (161 mg, 71%),
1
3
mp. 83 - 85 °C. H NMR (300 MHz, CDCl ) δ = 8.31 (s, 1H, CH ), 8.06 (d, J = 8.5 Hz, 1H,
3
Ar
3
4
3
CH ), 7.98 (dd, J = 7.8 Hz, J = 1.5 Hz, 2H, CH ), 7.68 (d, J = 8.0 Hz, 1H, CH ), 7.65 –
Ar
Ar
Ar
3
7
.57 (m, 1H, CH ), 7.48 – 7.37 (m, 4H, CH ), 7.11 (d, J = 5.3 Hz, 3H, CH ), 7.06 – 6.99
Ar Ar Ar
1
3
(
m, 1H, CH ), 2.22 (s, 3H, CH ). C NMR (75 MHz, CDCl ) δ = 158.9 (C ), 146.4 (C ),
Ar 3 3 Ar Ar
1
40.2 (CH ), 139.3 (C ), 137.7 (C ), 131.6 (CH ), 129.9 (CH ), 129.3 (2CH ), 129.2
Ar Ar Ar Ar Ar Ar
(2CH ), 128.6 (CH ), 128.1 (CH ), 127.9 (CH ), 127.6 (2CH ), 126.7 (CH ), 126.6
Ar Ar Ar Ar Ar Ar
(
CH ), 126.0 (C ), 122.4 (C ), 115.9 (C ), 94.5 (CAlkyne), 87.3 (CAlkyne), 20.9 (CH3).
Ar
Ar
Ar
Ar
-1
IR (ATR, cm ): ṽ = 3041 (w), 2965 (w), 2914 (w), 2852 (w), 2728 (w), 2345 (w), 2213 (w),
1
7
956 (w), 1814 (w), 1597 (m), 1579 (m), 1480 (m), 1441 (m), 1407 (m), 906 (m), 863 (m),
85 (m), 767 (m), 752 (s), 718 (m), 688 (s), 611 (m), 603 (m), 515 (m), 475 (m). MS
+
(
EI, 70 eV): m/z (%) = 320 (19), 319 ([M] , 85), 318 (100), 317 (12), 316 (17), 315 (9), 305
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European Journal of Organic Chemistry
10.1002/ejoc.201900913
2
7
(12), 304 (50), 303 (27), 302 (13), 301 (7), 213 (8), 152 (10),151 (7). HRMS (ESI):
+
Calculated for C H N [M+H] 320.1434 found 320.1435.
2
4
17
2
-Phenyl-3-(o-tolylethynyl)quinoline 3d
3
-Bromo-2-phenylquinoline 2a (0.7 mmol), alkyne (1.0 mmol), Pd(PPh ) Cl (0.035 mmol)
3
2
2
and CuI (0.07 mmol) in 6.0 ml of triethylamine gave 3d as pale yellow solid (207 mg, 92%),
1
3
mp. 123 - 125 °C. H NMR (300 MHz, CDCl ) δ = 8.47 (s, 1H, CH , 8.21 (d, J = 8.5 Hz,
3
Ar)
3
4
3
1
7
H, CH ), 8.09 (dd, J = 7.9 Hz, J = 1.7 Hz, 2H, CH ), 7.84 (d, J = 8.1 Hz, 1H, CH ),
Ar
Ar
Ar
3
3
4
.76 (ddd, J = 8.4 Hz, J = 6.9 Hz, J = 1.5 Hz, 1H, CH ), 7.62 – 7.50 (m, 4H, CH ), 7.44
Ar
Ar
3
13
(
d, J = 7.6 Hz, 1H, CH ), 7.27 – 7.15 (m, 3H, CH ), 2.36 (s, 3H, CH ). C NMR (75 MHz,
Ar Ar 3
CDCl ) δ = 158.9 (C ), 146.4 (C ), 140.3 (CH ), 139.9 (C ), 139.5 (C ), 131.6 (CH ),
3
Ar
Ar
Ar
Ar
Ar
Ar
1
1
29.9 (CH ), 129.2 (2CH ), 129.2 (CH ), 129.1 (CH ), 128.6 (CH ), 128.3 (2CH ),
Ar Ar Ar Ar Ar Ar
27.7 (CH ), 126.7 (CH ), 126.6 (CH ), 126.0 (C ), 125.2 (CH ), 122.3 (C ), 116.2
Ar
Ar
Ar
Ar
Ar
Ar
-
1
(
(
(
C ), 93.4 (CAlkyne), 91.1 (CAlkyne), 20.2 (CH ). IR (ATR, cm ): ṽ = 3051 (w), 3035 (w), 2921
Ar 3
w), 2852 (w), 2209 (w), 1599 (w), 1575 (w), 1480 (m), 1455 (m), 1441 (m), 1410 (m), 1366
m), 907 (m), 766 (m), 756 (m), 748 (s), 718 (m), 695 (s), 452 (m). MS (EI, 70 eV):
+
m/z (%) = 320 (15), 319 ([M] , 71), 318 (100), 317 (47), 316 (34), 315 (9), 304 (9), 213 (9),
1
59 (11), 152 (6), 139 (5), 77 (7), 76 (6), 51 (6). HRMS (ESI): Calculated for C H N
24 17
+
[
M+H] 320.1434 found 320.1435.
3
-((4-Ethylphenyl)ethynyl)-2-phenylquinoline 3e
-Bromo-2-phenylquinoline 2a (0.7 mmol), alkyne (1.0 mmol), Pd(PPh ) Cl (0.035 mmol)
3
3
2
2
and CuI (0.07 mmol) in 6.0 ml of triethylamine gave 3e as yellow solid (214 mg, 91%),
1
3
mp. 88 - 90 °C. H NMR (300 MHz, CDCl ) δ = 8.43 (s, 1H, CH ), 8.19 (d, J = 8.4 Hz, 1H,
3
Ar
3
3
CH ), 8.15 – 8.09 (m, 2H, CH ), 7.80 (d, J = 8.1 Hz, 1H, CH ), 7.73 (ddd, J = 8.4 Hz,
Ar
Ar
Ar
3
4
3
J = 6.9 Hz, J = 1.5 Hz, 1H, CH ), 7.60 – 7.49 (m, 4H, CH ), 7.35 (d, J = 8.2 Hz, 2H,
Ar
Ar
3
3
CH ), 7.18 (d, J = 8.3 Hz, 2H, CH ), 2.67 (q, J = 7.6 Hz, 2H, CH -CH ), 1.25 (t,
Ar
Ar
2
3
3
13
J = 7.6 Hz, 3H, CH -CH ). C NMR (75 MHz, CDCl ) δ = 158.9 (C ), 146.4 (C ), 144.7
2
3
3
Ar
Ar
(
C ), 140.0 (CH ), 139.3 (C ), 131.0 (2CH ), 129.8 (CH ), 129.3 (2CH ), 129.2 (CH ),
Ar Ar Ar Ar Ar Ar Ar
1
28.6 (CH ), 127.6 (2CH ), 127.5 (2CH ), 126.7 (CH ), 126.6 (CH ), 126.0 (C ), 119.7
Ar Ar Ar Ar Ar Ar
(
C ), 116.1 (C ), 94.6 (CAlkyne), 87.0 (CAlkyne), 28.5 (CH -CH ), 14.9 (CH -CH ).
Ar Ar 2 3 2 3
-1
IR (ATR, cm ): ṽ = 3056 (w), 3041 (w), 3023 (w), 2967 (w), 2930 (m), 2872 (w), 2213 (w),
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European Journal of Organic Chemistry
10.1002/ejoc.201900913
2
8
1
510 (m), 1480 (m), 1413 (m), 1368 (m), 914 (m), 832 (m), 768 (m), 750 (m), 718 (m), 695
+
(
s), 538 (m), 478 (m). MS (EI, 70 eV): m/z (%) = 334 (25), 333 ([M] , 100), 332 (64), 319
(14), 318 (59), 317 (38), 316 (36), 315 (20), 314 (10), 305 (12), 304 (50), 303 (16), 302 (10),
+
1
59 (13), 157 (9). HRMS (ESI): Calculated for C H N [M+H] 334.1590 found 334.1593.
2
5
19
3
-((4-Methoxyphenyl)ethynyl)-2-phenylquinoline 3f
3
-Bromo-2-phenylquinoline 2a (0.7 mmol), alkyne (1.0 mmol), Pd(PPh ) Cl (0.035 mmol)
3
2
2
and CuI (0.07 mmol) in 6.0 ml of triethylamine gave 3f as yellow solid (169 mg, 67%),
1
3
mp. 81 - 83 °C. H NMR (300 MHz, CDCl ) δ = 8.27 (s, 1H, CH ), 8.05 (d, J = 8.4 Hz, 1H,
3
Ar
3
4
3
CH ), 7.98 (dd, J = 8.0 Hz, J = 1.6 Hz, 2H, CH ), 7.66 (d, J = 8.1 Hz, 1H, CH ), 7.59
Ar
Ar
Ar
3
3
4
(
ddd, J = 8.4 Hz, J = 6.9 Hz, J = 1.5 Hz, 1H, CH ), 7.46 – 7.36 (m, 4H, CH ), 7.27 – 7.19
Ar Ar
1
3
(
m, 2H, CH ), 6.77 – 6.70 (m, 2H, CH ), 3.68 (s, 3H, OCH ). C NMR (75 MHz, CDCl )
Ar
Ar
3
3
δ = 159.9 (C ), 159.3 (C ), 146.7 (C ), 140.1 (CH ), 139.8 (C ), 132.9 (2CH ), 130.2
Ar
Ar
Ar
Ar
Ar
Ar
(
CH ), 129.7 (2CH ), 129,5 (CH ) 129.0 (CH ), 127.9 (2CH ), 127.1 (CH ), 127.0
Ar Ar Ar Ar Ar Ar
(
CH ), 126.4 (C ), 116.6 (C ), 115.1 (C ), 114.1 (2CH ), 94.9 (CAlkyne), 86.8 (CAlkyne),
Ar Ar Ar Ar Ar
-1
5
5.3 (OCH ). IR (ATR, cm ): ṽ = 3051 (w), 3010 (w), 2974 (w), 2934 (w), 2837 (w), 2540
3
(
(
(
(
w), 2209 (w), 1604 (m), 1508 (m), 1480 (m), 1293 (m), 1248 (m), 1171 (m), 1106 (m), 1026
m), 1006 (m), 909 (m), 828 (s), 767 (m), 747 (m), 720 (m), 698 (s), 535 (m), 477 (m). MS
+
EI, 70 eV): m/z (%) = 336 (24), 335 ([M] , 100), 334 (26), 321 (23), 320 (91), 292 (25), 291
75), 290 (47), 289 (10), 265 (10), 264 (10), 187 (11), 146 (22). HRMS (ESI): Calculated for
+
C H NO [M+H] 336.1383 found 336.1384.
24
17
3
-((4-Fluorophenyl)ethynyl)-2-phenylquinoline 3g
3
-Bromo-2-phenylquinoline 2a (0.7 mmol), alkyne (1.0 mmol), Pd(PPh ) Cl (0.035 mmol)
3
2
2
and CuI (0.07 mmol) in 6.0 ml of triethylamine gave 3g as white solid (208 mg, 92%),
1
3
mp. 128 - 130 °C. H NMR (300 MHz, CDCl ) δ = 8.43 (s, 1H, CH ), 8.16 (d, J = 8.5 Hz,
3
Ar
3
3
1
H, CH ), 8.09 – 8.02 (m, 2H, CH ), 7.82 (d, J = 8.1 Hz, 1H, CH ), 7.74 (ddd, J = 8.4 Hz,
Ar Ar Ar
3
4
J = 7.0 Hz, J = 1.3 Hz, 1H, CH ), 7.60 – 7.48 (m, 4H, CH ), 7.41 – 7.33 (m, 2H, CH ),
Ar
Ar
Ar
1
3
1
7
1
.08 – 6.98 (m, 2H, CH ). C NMR (75 MHz, CDCl ) δ = 162.7 (d, J = 250.3 Hz, CFAr),
Ar 3 CF
3
59.3 (C ), 146.9 (C ), 140.5 (CH ), 139.7 (C ), 133.3 (d, J = 8.4 Hz, 2CH ), 130.4
Ar
Ar
Ar
Ar
CF
Ar
(
CH ) , 129.6 (2CH ), 129.0 (2CH ), 127.9 (2CH ), 127.1 (2CH ), 126.3 (C ), 119.1 (d,
Ar Ar Ar Ar Ar Ar
4
2
JCF = 3.5 Hz, C ), 116.1 (C ), 115.1 (d, J = 22.2 Hz, 2CH ), 93.5 (CAlkyne), 87.7
Ar
Ar
CF
Ar
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European Journal of Organic Chemistry
10.1002/ejoc.201900913
2
9
1
9
-1
(
CAlkyne). F NMR (282 MHz, CDCl ) δ = -110.10 (CF ). IR (ATR, cm ): ṽ = 3051 (w),
3 Ar
3
1
038 (w), 2922 (w), 2852 (w), 2216 (w), 1899 (w), 1584 (w), 1505 (m), 1480 (m), 1234 (m),
223 (m), 1155 (m), 915 (m), 836 (m), 768 (m), 750 (m), 719 (m), 696 (s), 534 (m). MS
+
(
EI, 70 eV): m/z (%) = 324 (12), 323 (61), 322 ([M] , 100), 321 (19), 320 (11), 218 (6), 161
(
7). HRMS (EI): Calculated for C H FN 322.1027 found 322.1025.
2
3
13
2
-Phenyl-3-(thiophen-3-ylethynyl)quinoline 3h
3
-Bromo-2-phenylquinoline 2a (0.7 mmol), alkyne (1.0 mmol), Pd(PPh ) Cl (0.035 mmol)
3
2
2
and CuI (0.07 mmol) in 6.0 ml of triethylamine gave 3h as white solid (207 mg, 95%),
1
3
mp. 117 - 119 °C. H NMR (300 MHz, CDCl ) δ = 8.34 (s, 1H, CH ), 8.09 (d, J = 8.5 Hz,
3
Ar
3
3
1
H, CH ), 8.02 – 7.94 (m, 2H, CH ), 7.72 (d, J = 8.1 Hz, 1H, CH ), 7.64 (ddd, J = 8.4 Hz,
Ar Ar Ar
3
4
3
J = 6.9 Hz, J = 1.5 Hz, 1H, CH ), 7.51 – 7.38 (m, 4H, CH ), 7.34 (dd, J = 3.0 Hz,
Ar
Ar
4
3
4
J = 1.1 Hz, 1H, CH ), 7.22 – 7.16 (m, 1H, CH ), 7.00 (dd, J = 5.0 Hz, J = 1.1 Hz, 1H,
Ar
Ar
1
3
CH ). C NMR (75 MHz, CDCl ) δ = 159.2 (C ), 146.7 (C ), 140.4 (CH ), 139.5 (C ),
Ar
3
Ar
Ar
Ar
Ar
1
1
30.3 (CH ), 129.6 (2CH ), 129.5 (2CH ), 129.0 (CH ), 129.0 (CH ), 127.9 (2CH ),
Ar Ar Ar Ar Ar Ar
27.1 (CH ), 127.0 (CH ), 126.3 (C ), 125.5 (CH ), 122.0 (C ), 116.2 (C ), 90.0
Ar
Ar
Ar
Ar
Ar
Ar
-
1
(
(
(
CAlkyne), 87.4 (CAlkyne). IR (ATR, cm ): ṽ = 3105 (w), 3083 (w), 3057 (w), 3037 (w), 2922
w), 2853 (w), 2209 (w), 1820 (w), 1586 (w), 1554 (w), 1480 (m), 1422 (m), 1400 (m), 1367
m), 1355 (m), 912 (m), 865 (m), 769 (s), 750 (m), 696 (s), 622 (m), 477 (m). MS (EI, 70 eV):
+
m/z (%) = 313 (4), 312 (17), 311 ([M] , 66), 310 (100), 309 (19), 308 (5), 264 (6), 163 (7),
+
1
55 (6). HRMS (ESI): Calculated for C H NS [M+H] 312.0842 found 312.0842.
2
1
13
3
-(Phenylethynyl)-2-(p-tolyl)quinoline 3i
-Bromo-2-phenylquinoline 2b (0.7 mmol), alkyne (1.0 mmol), Pd(PPh ) Cl (0.035 mmol)
3
3
2
2
and CuI (0.07 mmol) in 6.0 ml of triethylamine gave 3i as white solid (199 mg, 93%),
1
3
mp. 133 – 135 °C. H NMR (250 MHz, CDCl ) δ = 8.44 (s, 1H, CH ), 8.17 (d, J = 8.5 Hz,
3
Ar
3
3
1
H, CH ), 8.06 – 8.00 (m, 2H, CH ), 7.81 (d, J = 8.1 Hz, 1H, CH ), 7.73 (ddd, J = 8.4 Hz,
Ar Ar Ar
3
4
3
3
4
J = 6.9 Hz, J = 1.5 Hz, 1H, CH ), 7.55 (ddd, J = 8.1 Hz, J = 7.0 Hz, J = 1.2 Hz, 1H,
Ar
13
CH ), 7.48 – 7.41 (m, 2H, CH ), 7.37 – 7.32 (m, 5H, CH ), 2.47 (s, 3H, CH ). C NMR
Ar
Ar
Ar
3
(
(
(
63 MHz, CDCl ) δ = 159.3 (C ), 147.0 (C ), 140.9 (CH ), 139.2 (C ), 136.9 (C ), 131.5
3 Ar Ar Ar Ar Ar
2CH ), 130.4 (CH ), 129.7 (2CH ), 129.6 (CH ), 128.8 (2CH ), 128.7 (CH ), 128.5
Ar
Ar
Ar
Ar
Ar
Ar
2CH ), 127.2 (CH ), 127.0 (CH ), 126.4 (C ), 123.2 (C ), 116.3 (C ), 94.6 (CAlkyne),
Ar
Ar
Ar
Ar
Ar
Ar
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