Synthesis of aryl-substituted quinolines and tetrahydroquinolines through Suzuki–Miyaura coupling reactions

Article abstract of DOI:10.1177/1747519819861389

The synthesis and characterization of substituted (trifluoromethoxy, thiomethyl, and methoxy) phenyl quinolines is described. Dichlorobis(triphenylphosphine)palladium(II)-catalyzed Suzuki–Miyaura cross-coupling of 6-bromo- and 6,8-dibromo-1,2,3,4-tetrahyd

Full text of DOI:10.1177/1747519819861389

861389CHL0010.1177/1747519819861389Journal of Chemical ResearchÖkten
research-article2019
Research Paper
Journal of Chemical Research
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Synthesis of aryl-substituted quinolines
and tetrahydroquinolines through
Suzuki–Miyaura coupling reactions
https://doi.org/10.1177/1747519819861389
DOI: 10.1177/1747519819861389
journals.sagepub.com/home/chl
Salih Ökten
Abstract
The synthesis and characterization of substituted (trifluoromethoxy, thiomethyl, and methoxy) phenyl quinolines is
described. Dichlorobis(triphenylphosphine)palladium(II)-catalyzed Suzuki–Miyaura cross-coupling of 6-bromo- and
6,8-dibromo-1,2,3,4-tetrahydroquinolines, 5-bromo-8-methoxyquinoline, and 5,7-dibromo-8-methoxyquinoline with
substituted phenylboronic acids affords the corresponding 6-aryl- (13a–d), 6,8-diaryl- (14a–c), 5-aryl- (15), and
5,7-diaryl- (16b, c) tetrahydroquinolines and quinolines in high yields (68%–82%). The structures of all the products are
characterized by 1H NMR, 13C NMR,19F NMR, and Fourier transform infrared spectroscopy and by elemental analysis.
Keywords
aryl quinolines, nuclear magnetic resonance spectroscopy, quinolines, substituted phenyls, Suzuki–Miyaura cross-
coupling, tetrahydroquinolines
Date received: 5 March 2019; accepted: 13 June 2019
halogen-substituted tetrahydroquinolines (Scheme 1) as key
Introduction
Quinoline derivatives are found in many natural products1
compounds and as precursors for numerous bioactive quino-
line derivatives.15
and synthetic drugs.2 The quinoline scaffold has been used
Arylated quinolines were previously prepared by clas-
to develop compounds exhibiting a wide range of medici-
sic reactions, such as the Skraup, Doebner–Miller, Conrad–
nal benefits,3,4 such as anti-asthmatic, anti-inflammatory,
Limpach, Friedländer, and Pfitzinger syntheses.16 Arylated
antimalarial,4 anticancer,5 and antibiotic activity.6
quinolines are also prepared by cross-coupling reactions
Tetrahydroquinolines have an important position in syn-
and other transition-metal-catalyzed transformations.17–19
thetic organic chemistry due to the fact they possess high
For example, arylated quinolines were prepared by
reactivity, a wide spectrum of chemical properties7 and
form the basis of many bioactive natural substances8–12 and
potential drugs.13,14
Halogenated tetrahydroquinoline derivatives are impor-
tant initiators of progress in new methods for the develop-
mentofmedicinalchemistry. Intheliterature, thehalogenation
of 1,2,3,4-tetrahydroquinoline (1) is accomplished with halo-
gens (bromine, chlorine, etc.), N-halosuccinimides, aqueous
solutions of sodium chlorate and bromate, affording various
Department of Maths and Science Education, Faculty of Education,
Kırıkkale University, Kırıkkale, Turkey
Corresponding author:
Salih Ökten, Department of Maths and Science Education, Faculty of
Education, Kırıkkale University, Yahşihan, 71450 Kırıkkale, Turkey.
Emails: salihokten@kku.edu.tr; sokten@gmail.com

2
Journal of Chemical Research 00(0)
Suzuki–Miyaura coupling of arylboronic acids with
Previously, we carried out the bromination of 1,2,3,4-tet-
haloaromatic compounds.20 Although numerous studies on rahydroquinoline (1)15,35,36 with molecular bromine leading
the transformation of haloquinolines into aryl quinolines to the formation of polyfunctional quinoline derivatives,
are reported in the literature, there are fewer reports on the which was followed by transformation into their respective
preparation of aryl tetrahydroquinolines. For example, derivatives.35,37–39 As an extension of the investigation of
Mphahlele et al. were interested in the palladium-catalyzed 1,2,3,4-tetrahydroquinoline (1) derivatives, we studied the
cross-coupling reactions of dihalogenoquinolines for the regioselective bromination of methoxy-, cyano-, hydroxy-,
preparation of substituted tetrahydroquinolines and and amino-substituted quinolines38,40,41 with bromine under
decided to investigate the synthesis of 2-aryl-6,8-dibromo- different conditions. The polyfunctional substituted quino-
1,2,3,4-tetrahydroquinolines (8) (Scheme 2).21–23 In other lines were tested for their anticancer potentials and enzyme
work, 5,7-diarylquinolines were prepared by Suzuki– inhibition activities. It was found that substituted quinolines
Miyaura coupling of 5,7-dihalogenated quinolines.24 with different functional groups, especially 6,8-dibromo-
Moreover, the synthesis of arylated quinolines was 1,2,3,4-tetrayhdroquinoline (3),42 5,7-dibromo-8-methox-
reported by Suzuki–Miyaura reactions of 5,7-dibromo-8- yquinoline (6),43 5,7-dibromo-8-hydroxyquinoline,43 and
(trifluoromethylsulfonyloxy)quinoline (11) (Scheme 2).25
6,8-diphenylquinoline44 had anticancer activities against
In the literature, many studies on the pharmacological HeLa (human cervix carcinoma), HT29 (human colon carci-
features of aryl-substituted quinolines have been reported. noma), C6 (rat glioblastoma), and MCF7 (human breast
The 6- or 8-aryl substituted 2,4-dimethoxyquinolines were adenocarcinoma) cell lines, and monophenyl-substituted
found to exhibit high activity against the agriculturally quinolines showed inhibitory effects on AChE (acetylcho-
important nematode, Haemonchus contortus.26 Furthermore, linesterase), BChE (butyrylcholinesterase), and carbonic
2-phenyl-quinoline-4-carboxylic acid derivatives were found anhydrase isoenzymes I and II (hCA I and II).20
to have significant effects on antibacterial activity.27 In other
The promising anticancer activities of the analogous
work on phenyl quinolines, 2-(4-phenylquinolin-2-yl)phenol 6,8-dibromotetrahydroquinoline (3), 6,8-diphenylquino-
derivatives produced significant anti-inflammatory, analge- line, and 5,7-dibromo-8-(hydroxy/methoxy)quinolines
sic and antipyretic activities and demonstrated efficient inhi- encouraged us to synthesize novel and potentially bioac-
bition of the COX-2 enzyme.28 A number of substituted tive quinoline compounds. Based on our continued inter-
2-phenylquinolines displayed superior ERβ affinity in a cell- est in the palladium-catalyzed cross-coupling reactions of
based transcriptional assay,29 potent antiplatelet activities,30 bromoquinolines,44 we herein describe the Suzuki–
antimitotic activity,31–33 and antiproliferative activity against Miyaura cross-coupling reactions of 6-bromo- and
the growth of certain cancer cells such as HCT-116 (colon 6,8-dibromo-1,2,3,4-tetrahydroquinolines (2 and 3), and
cancer), MCF7 (breast cancer), and MDA-MB-435 (breast 5-bromo- and 5,7-dibromo-8-methoxyquinolines (5 and
cancer) with low GI50 values.34
6) with substituted arylboronic acids to afford aryl-substi-
tuted tetrahydroquinoline and quinoline derivatives
(Scheme 3).
Results and discussions
Attempted Suzuki–Miyaura cross-coupling of 6-bromo-
1,2,3,4-tetrahydroquinoline (2) with
a mixture of
unsubstituted phenyl or 4-substituted (4-methoxy-, 4-tri-
fluoromethoxy-, and 4-thiomethylphenyl) phenylboronic
acids (1.0 equiv.) and 2 M K2CO3 in dimethylformamide
in the presence of tetrakis(triphenylphosphine)
Scheme 1. Preparation of brominated tetrahydroquinolines (2
and 3) and quinolines (5 and 6).
Scheme 2. Reported synthetic strategies toward arylated quinolines and tetrahydroquinolines.21–23,25

Ökten
3
Scheme 3. Synthetic strategies toward arylated quinolines and tetrahydroquinolines in this study.
Table 1. The yields and melting points of 13a–d and 14a–c.
Product
X
Ar
Yield (%)
M.p. (°C)
13a
13b
13c
13d
14a
14b
14c
H
H
H
H
81
73
68
76
80
78
82
55–57
71–73
82–84
100–101
73–75
palladium(0) (Pd(PPh3)4) afforded 6-phenyl-, 6-(4-meth- 3J=5.4Hz and 2.85–2.81, 3J=6.3Hz; 3.35–3.31, 3J=5.4Hz
ylthio)phenyl-, 6-(4-trifluoromethoxy)phenyl-,
and and 2.85–2.81, 3J=6.3Hz, respectively) and aliphatic multi-
6-(4-methoxy)phenyl-1,2,3,4-tetrahydroquinoline deriv- plet (2.02–1.94ppm for all compounds 13a–d) belong to the
atives in high yields (68%–81%). 6-Phenyl-1,2,3,4- characteristic H-2, H-4, and H-3 protons in the nitrogen-
tetrahydroquinoline (13a)45 and 6-(4-(trifluoromethoxy) containing rings of the tetrahydroquinolines (Figure 1).
phenyl]-1,2,3,4-tetrahydroquinoline (13b)46 were recent- Multiplets for the aryl H signals of the quinoline and phenyl
ly reported and the published spectral data confirmed the scaffolds of 13a–d were observed in the range of 6.91–
data obtained in this study. Moreover, 6,8-dibromo- 7.56ppm. The H-7 protons of 13a–d gave doublet signals at
1,2,3,4-tetrahydroquinoline (3) was treated with the same about 6.55ppm (Figure 1). Moreover, the singlets in the 1H
phenylboronic acids under identical reaction conditions NMR spectra of 13c and 13d at 2.52 and 3.84ppm, respec-
to give 6,8-diphenyl-, 6,8-bis[4-(methylthio)phenyl)-, tively, verified the attachment of the 4-(methylthio)phenyl
and
6,8-bis(4-(trifluo-romethoxy)phenyl]-1,2,3,4-tet- and 4-(methoxy)phenyl groups at C-6 of the quinoline ring
rahydroquinolines in yields of 80%, 82%, and 78%, (Figure 1). In the 13C NMR spectra of compounds 13a–d,
respectively (Table 1).
three aliphatic carbon resonances (approx. 22.2, 27.1,
The structures of all substituted phenyl-containing com- 42.0ppm) in the sp3 region and ten aromatic carbon reso-
pounds 13a–d were confirmed by 1H and 13C NMR, Fourier nances are also in agreement with the suggested structures.
1
2
transform infrared (FTIR), and elemental analysis. The H Moreover, the signals at 122.5 (q, JC, F =260Hz, OCF3),
NMR signals of coupled compounds 13a–d are similar to 16.5 (SCH3), and 55.6 (OCH3)ppm are consistent with pro-
starting material 2 except for the aromatic phenyl signals. posed structures 13b, 13c, and 13d, respectively. In the 19
F
The aliphatic triplets in the 1H NMR spectra of compounds NMR spectrum of 13b, a singlet at −58.2ppm provided evi-
3
3
13a–d (3.39–3.35, J=5.6Hz and 2.88–2.83, J=6.4Hz; dence for the 4-(trifluoromethoxy)phenyl at the C-6 position
3.37–3.33, 3J=5.4Hz and 2.86–2.81, 3J=6.3Hz; 3.36–3.32, of the quinoline.

4
Journal of Chemical Research 00(0)
Our recent publications showed that cyano-38 and methoxy-
substituted41 tetrahydroquinolines underwent further bro-
mination to give 3-brominated aromatic derivatives.
6-Aryl-8-bromotetrahydroquinoline and 6-aryl-3,8-dibro-
moquinoline derivatives can be obtained by bromination of
6-aryltetrahydroquinolines 13a–d in two steps by our
developed methods.15,35,47 Also, these arylbromoquinolines
can be transformed into substituted quinolines bearing dif-
ferent substituents by exchanging the bromine atom with
different functional groups via metal-catalyzed substitu-
tion35,48 or coupling reactions.20 Therefore, substituted qui-
nolines bearing three different groups at C-3, C-5, and C-8
can be synthesized.
In our previous publication,40 the direct bromination of
8-methoxyquinoline was reinvestigated and treatment of
8-methoxyquinoline with different equivalents of molecular
bromine afforded 5-bromo-8-methoxyquinoline (5) and
5,7-dibromo-8-methoxyquinoline (6). In this study, com-
pounds 5 and 6 were reacted with substituted phenylboronic
acids via Suzuki–Miyaura cross-coupling reactions. These
reactions furnished 8-methoxy-5-(4-(trifluoromethoxy)phe-
nyl]quinoline (15), 8-methoxy-5,7-bis[4-(trifluoromethoxy)
phenyl)quinoline(16a)and8-methoxy-5,7-bis(4-(methylthio)
phenyl) (16b) in good yields (70%–85%) (Table 2).
1
The H and 13C NMR, IR, and elemental analysis sup-
ported the assignment of compounds 15 and 16a,b contain-
ing substituted phenyl groups. The 1H NMR spectrum of 15
indicated the presence of an OCH3 signal at 4.08ppm, a
characteristic doublet of doublets at 8.92ppm (3J=3.9Hz,
4J=1.8Hz) corresponding to H-2, two doublets at 8.13
(3J=8.4Hz, H-4) and 7.06 (3J=8.4Hz, H-7)ppm, and six
aromatic protons as a multiplet at 7.28–7.42ppm. Moreover,
in the 19F NMR spectrum of 15, the singlet appearing at
−58.2ppm was consistent with the proposed structure.
These data led to the assignment of 15 as 8-methoxy-5-(4-
(trifluoromethoxy)phenyl)quinoline. In the 1H NMR spec-
trum of 16a, a characteristic doublet of doublets at 9.00ppm
(3J=4.2Hz, 4J=1.5Hz) corresponding to H-2, a doublet at
8.23ppm (3J=8.4Hz) belonging to H-4, another doublet of
doublets at 7.45ppm (3J=8.4Hz, 3J=4.2Hz, H-3), a singlet
due to OCH3 at 3.87ppm and the aromatic signals at 7.32–
7.39 (m, 4H), 7.52 (d, 3J=9.6Hz, 3H), and 7.77 (d,
3J=8.7Hz, 2H)ppm were consistent with the proposed
structure. Similarly, the assignment of 16b as 8-methoxy-
5,7-bis(4-(methylthio)phenyl]quinoline was based on its
1H NMR spectral data, which included two thiomethyl sin-
glets at 2.54 and 2.56ppm, a methoxy signal at 3.89ppm
and twelve aromatic proton signals.
1
Figure 1. H NMR spectra of 6-bromo-1,2,3,4-
tetrahydroquinoline (2) (top; starting material) and the coupling
derivatives 13a–d.
The 1H NMR spectra of 14a–c showed the formation of
diaryl (diphenyl, bis(4-trifluoromethoxy)phenyl, and bis(4-
methylthio)phenyl) tetrahydroquinolines. The aliphatic tri-
1
plets in the H NMR spectra of compound 14a–c (approx.
3.32 (3J=5.4Hz) and 2.92 (3J=6.3Hz)ppm) and aliphatic
multiplets (approx. 2.00ppm) belong to the characteristic
H-2, H-4, and H-3 protons in the nitrogen-containing ring of
1
the tetrahydroquinolines. The H NMR spectrum of com-
pound 14a displayed multiplets for the aryl H signals of the
quinoline and phenyl scaffolds in the range of 7.26–7.62ppm
while the aryl protons of 14c gave multiplet signals at higher
field (7.15–7.48ppm) due to the electron-rich feature of the
methylthio group. Moreover, the two singlets in the spec-
trum of 11c at 2.50 and 2.53ppm and the appearance of two
singlets in the 19F NMR spectrum of 14b at −58.2 and
−58.3ppm indicated the attachment of the 4-(methylthio)
phenyl and 4-(trifluoromethoxy)phenyl groups, respec-
tively, at the C-6 and C-8 positions of the quinoline ring.
The high reactivities of 13a–d and 14a–c toward halo-
genation should enable them to act as valuable precursors
for novel compounds used in a wide range of applications.
Conclusion
In conclusion, we have demonstrated that the Suzuki–Miyaura
cross-coupling
6,8-dibromo-1,2,3,4-tetrahydroquinoline,
of
6-bromo-1,2,3,4-tetrahydroquinoline,
5-bromo-
8-methoxyquinoline, and 5,7-dibromo-8-methoxyquinoline
with substituted phenylboronic acids occurs without selectivity
to afford the corresponding 6-aryl- (13a–d), 6,8-diaryl- (14a–
c), 5-aryl (15), and 5,7-diaryl- (16a,b) tetrahydroquinolines and
quinolines in a single-pot reaction. The aryl-substituted

Ökten
5
Table 2. The yields and melting points of 15 and 16a,b.
Product
Ar1
H
Ar2
Yield (%)
M.p. (°C)
15
73
70
85
80–82
–
16a
16b
172–174
tetrahydroquinolines 13a–d and 14a–c could be important column chromatography (silica gel, hexane/EtOAc) to
starting materials for the synthesis of polyfunctionalized quino- afford the product.
line derivatives due to their high reactivity toward further bro-
6-Phenyl-1,2,3,4-tetrahydroquinoline (13a): Yellow oil,
mination.38,41 Studies are currently underway in our laboratory yield 81% (0.40g), Rf =0.41 (6:1, hexane/EtOAc). 1H NMR
to investigate the reactivity and biological properties of the syn- (400MHz, CDCl3): δ 1.58 (br s, 1H, NH), 1.99–2.03 (m,
3
3
thesized aryl-substituted quinolines.
2H, H3), 2.86 (t, J=6.4Hz, 2H, H4), 3.37 (t, J=5.6Hz,
2H, H2), 6.57 (d, 3J=7.6Hz, 1H, H7), 7.25–7.56 (m, 7H).
13C NMR (100MHz, CDCl3): δ 22.2, 27.1, 42.0, 114.4,
121.6, 125.5, 125.9, 126.3 (2C), 128.2, 128.6 (2C), 129.9,
141.5, 144.3. FTIR (cm−1): 3432, 3023, 2945, 2921, 2832,
1597, 1483, 1434, 1359, 1331, 1287, 1201, 1185, 1128,
Experimental
General
All the reagents and solvents were commercially available. 1100, 1073, 1025, 894, 861, 765, 699, 594, 575, 524, 498,
Thin-layer chromatography was carried out on Merck silica 454. Anal. calcd for C15H15N (209.12): C, 86.08; H, 7.22;
F254 0.255mm plates, and spots were visualized by UV fluo- N, 6.69; found: C, 86.24; H, 7.13; N, 6.62.
rescence at 254nm. Classic column chromatography was
6-(4-(Trifluoromethoxy)phenyl]-1,2,3,4-tetrahydroquino-
performed using Merck 60 (70–230mesh) silica gel. Melting line (13b): Brown solid, yield 73% (0.26g), m.p. 55–57°C.
points were determined on a Thomas–Hoover capillary Rf=0.43 (6:1, hexane/EtOAc). 1H NMR (300MHz, CDCl3): δ
melting point apparatus. Solvents were concentrated under 1.95–2.02 (m, 2H, H3), 2.84 (t, 2H, 3J=6.3Hz, H2), 3.35 (t,
reduced pressure. NMR spectra were recorded on an Oxford 3J=5.4Hz, 2H, H4), 3.63 (s, 1H, NH), 6.55 (d, 3J=9.0Hz, 1H,
Instruments Varian at 300MHz for 1H NMR, at 75MHz for H7), 7.19–7.26 (m, 4H), 7.49–7.55 (m, 2H). 13C NMR
13C NMR, and at 282MHz for 19F NMR. IR spectra were (75MHz, CDCl3): δ 22.3, 27.4, 42.2, 114.6, 119.1, 121.4 (2C),
2
recorded on a BrukerVertex 70v FTIR instrument. Elemental 121.8, 122.5 (q, JC, F =260Hz, OCF3), 125.7, 127.6 (2C),
analyses were recorded on an ElementarVario MICRO Cube 128.4, 128.6, 140.5, 144.9. 19F NMR (282MHz, CDCl3): δ
instrument. The NMR spectrums of all compounds are −58.2. FTIR (cm−1): 3450, 2953, 2836, 1610, 1526, 1493,
presented as Supplemental material.
1443, 1402, 1358, 1214, 1133, 1009, 922, 897, 845, 804, 664,
610, 579, 523, 430. Anal. calcd for C16H14F3NO (293.10): C,
One-pot Suzuki cross-coupling; general procedure. To a 65.52; H, 4.81; N, 4.78; found: C, 65.54; H, 4.83; N, 4.82.
solution of bromotetrahydroquinoline or bromoquino- 6-(4-(Methylthio)phenyl]-1,2,3,4-tetrahydroquinoline
line 2, 3, 5 or 6 (1.0 equiv.) in 1,4-dioxane (30 mL) in a (13c): Brown needles, yield 68% (0.20g), m.p. 71–73°C.
two-necked flask was added aq K2CO3 (3.0 M, 15 mL) Rf =0.25 (8:1, hexane/EtOAc). 1H NMR (300MHz, CDCl3):
and the mixture was stirred for 10 min at room tempera- δ 1.94–2.02 (m, 2H, H3), 2.52 (s, 3H, SCH3), 2.83 (t, 2H,
3
ture under an N2 atmosphere. Pd(PPh3)4 (0.05 equiv.) 3J=6.3Hz, 2H, H2), 3.34 (t, J=5.4Hz, 2H, H4), 3.70 (s,
and the unsubstituted or 4-substituted phenylboronic 1H, NH), 6.54 (d, 3J =9.3Hz, 1H, H7), 7.20–7.32 (m, 4H),
acid (1.3 equiv. for monobromides, 2.6 equiv. for dibro- 7.45–7.48 (m, 2H). 13C NMR (75MHz, CDCl3): δ 16.5
mides) were added. The mixture was refluxed for 4 h at (SCH3), 22.4, 27.4, 42.2, 114.8, 121.9, 125.5, 126.9 (2C),
90 ºC. The progress of the reaction was monitored by 127.5 (2C), 128.1, 129.5, 135.8, 138.8, 144.3. FTIR (cm−1):
TLC. After completion of the reaction, the mixture was 3308, 3030, 2944, 2924, 2837, 1612, 1585, 1522, 1487,
diluted with H2O and extracted with CHCl3 (3 × 20 mL). 1438, 1419, 1360, 1327, 1310, 1292, 1268, 1260, 1245,
The combined organic layers were dried over anhydrous 1180, 1143, 1093, 1075, 1007, 952, 908, 827, 801, 724,
Na2SO4, filtered, and the filtrate was concentrated under 691, 603, 572, 505. Anal. calcd for C16H17NS (255.11): C,
reduced pressure. The resulting residue was purified by 75.25; H, 6.71; N, 5.48; found: C, 75.34; H, 6.73; N, 5.52.

6
Journal of Chemical Research 00(0)
6-(4-Methoxyphenyl)-1,2,3,4-tetrahydroquinoline (2C), 134.2, 138.3, 140.3, 148.7, 149.4, 155.3. 19F NMR
(13d): Yellow solid, yield 76% (0.40g), m.p. 82–84°C. (282MHz, CDCl3): δ −58.2. FTIR (cm−1): 3064, 2966,
Rf =0.38 (8:1, hexane/EtOAc). 1H NMR (300MHz, CDCl3): 2943, 2841, 1575, 1509, 1469, 1440, 1370, 1256, 1204,
δ 1.94–2.02 (m, 2H, H3), 2.83 (t, 2H, 3J=6.3Hz, 2H, H2), 1159, 1109, 1021, 996, 917, 859, 813, 782, 720, 669, 639,
3
3.33 (t, J=5.4Hz, 2H, H4), 3.84 (s, 3H, OCH3), 6.54 (d, 595, 539, 491. Anal. calcd for C17H12F3NO2 (319.08): C,
3J=8.7Hz, 1H, H7), 6.91–6.96 (m, 2H), 7.17–7.20 (m, 63.95; H, 3.79; N, 4.39; found: C, 63.74; H, 3.90; N, 4.25.
2H), 7.43–7.48 (m, 2H). 13C NMR (75MHz, CDCl3): δ
8-methoxy-5,7-bis(4-(trifluoromethoxy)phenyl]quino-
22.5, 27.4, 42.3, 55.6 (OCH3), 114.3, 114.8, 121.9, 125.4, line (16a): Yellow oil, yield 70% (0.21g). Rf =0.38 (3:1,
1
127.5 (2C), 128.1, 130.0, 134.5, 144.0, 158.4. FTIR (cm−1): hexane/EtOAc). H NMR (300MHz, CDCl3): δ 3.87 (s,
3337, 3300, 2943, 2928, 2834, 1608, 1494, 1463, 1297, 3H, OCH3), 7.32–7.39 (m, 4H), 7.45 (dd, 3J=8.4Hz,
1272, 1238, 1179, 1040, 1021, 900, 822, 785, 725, 559, 3J=4.2Hz, 1H, H3), 7.52 (d, J=9.6Hz, 3H), 7.77 (d,
3
525, 453. Anal. calcd for C16H17NO (239.13): C, 80.30; H, 3J=8.7Hz, 2H), 8.23 (d, J=8.4Hz, 1H, H4), 9.00 (dd,
3
7.16; N, 5.85; found: C, 80.34; H, 7.13; N, 5.82.
4J=1.5Hz, 3J=4.2Hz, 1H, H2). 13C NMR (75MHz,
2
6,8-Diphenyl-1,2,3,4-tetrahydroquinoline (14a): White CDCl3): δ 62.3, 116.6, 119.0 (q, JC, F =256.5Hz, OCF3),
solid, yield 80% (1.25g), m.p. 100–101°C. Rf =0.51 (6:1, 121.1 (2C), 121.4 (2C), 121.9, 122.4, 122.7, 127.7, 130.0,
hexane/EtOAc). 1H NMR (400MHz, CDCl3): δ 2.02–2.06 131.2 (2C), 131.6 (2C), 132.2, 136.5, 137.7, 143.2, 149.0,
(m, 2H, H3), 2.96 (t, 3J=6.0Hz 2H, H2), 3.33 (t, 3J=6.0Hz, 149.2, 150.2, 153.2. 19F NMR (282MHz, CDCl3): δ −58.1,
2H, H4), 4.14 (s, 1H, NH), 7.26–7.62 (m, 12H). 13C NMR −58.2. FTIR (cm−1): 2917, 2848, 1742, 1601, 1510, 1462,
(100MHz, CDCl3): δ 22.0, 27.7, 42.1, 121.6, 126.0, 126.3 1392, 1354, 1249, 1207, 1162, 1105, 1077, 1019, 990, 922,
(2C), 126.8, 126.9, 127.2, 127.5, 128.6 (2C), 128.8, 128.9 881, 847, 797, 714, 678, 612, 591, 565, 530. Anal. calcd for
(2C), 129.2, 129.4 (2C), 139.5, 141.3. FTIR (cm−1): 3322, C24H15F6NO3 (479.10): C, 60.13; H, 3.15; N, 2.92; found:
3044, 2939, 2843, 2722, 1594, 1498, 1472, 1363, 1301, C, 60.24; H, 3.10; N, 2.95.
1225, 1167, 1152, 1071, 1024, 1000, 886, 827, 810, 752,
8-Methoxy-5,7-bis(4-(methylthio)phenyl)quinoline
691, 618, 594, 531, 508, 456. Anal. calcd for C21H19N (16b): Yellow solid, yield 85% (0.14g), m.p. 172–174°C.
(285.15): C, 88.38; H, 6.71; N, 4.91; found: C, 88.34; H, Rf =0.51 (6:1, hexane/EtOAc). 1H NMR (300MHz, CDCl3):
6.73; N, 4.87.
δ 2.54 (s, 3H, SCH3), 2.56 (s, 3H, SCH3), 3.89 (s, 3H,
6,8-Bis(4-(trifluoromethoxy)phenyl]-1,2,3,4-tetrahyd- OCH3), 7.34–7.42 (m, 7H), 7.52 (s, 1H, H6) 7.68 (d,
roquinoline (14b): Light brown oil, yield 78% (0.53g), 3J=8.4Hz, 2H), 8.24 (dd, 3J=8.7Hz, 4J=1.5Hz, 1H, H4),
Rf =0.40 (9:1, hexane/EtOAc). 1H NMR (300MHz, CDCl3): 9.00 (dd, 4J=1.5Hz, 3J=3.9Hz, 1H, H2). 13C NMR
δ 1.97–2.01 (m, 2H, H3), 2.92 (t, 3J=6.3Hz, 2H, H2), 3.32 (75MHz, CDCl3): δ 15.9, 16.0, 62.2, 121.4, 126.4 (2C),
(t, 3J=5.4Hz, 2H, H4), 4.10 (br s, 1H, NH), 7.14–7.34 (m, 126.7 (2C), 127.5, 129.7, 130.1 (2C), 130.7 (2C), 132.7,
6H), 7.48–7.57 (m, 4H). 13C NMR (75MHz, CDCl3): δ 134.7, 134.8, 135.6, 136.0, 138.2, 138.4, 143.6, 150.1,
22.1, 27.9, 42.8, 119.3 (q, JC, F =264.8Hz, OCF3), 121.5 152.7. FTIR (cm−1): 3023, 2920, 2835, 1904, 1596, 1492,
2
(2C), 121.8 (2C), 122.2, 122.7, 125.8, 127.0, 127.6 (2C), 1454, 1427, 1380, 1340, 1267, 1222, 1189, 1077, 989, 960,
128.1, 128.2, 129.1, 130.2 (2C), 138.4, 140.3, 141.8, 148.0, 924, 823, 805, 727, 695, 509, 484, 437. Anal. calcd for
148.8. 19F NMR (282MHz, CDCl3): δ −58.2, −58.3. FTIR C24H21NOS2 (403.11): C, 71.43; H, 5.25; N, 3.47; found: C,
(cm−1): 3433, 2935, 2843, 1605, 1493, 1470, 1449 1339, 71.28; H, 5.20; N, 3.55.
1247, 1203, 1158, 1104, 1018, 921, 844, 806, 679, 652,
543. Anal. calcd for C23H17F6NO2 (453.12): C, 60.93; H, Acknowledgement
3.78; N, 3.09; found: C, 60.84; H, 3.73; N, 3.05.
The author is thankful to research assistant Yavuz Derin for his
6,8-Bis(4-(methylthio)phenyl]-1,2,3,4-tetrahydroquino-
line (14c): Yellow cubic, yield 82% (1.06g), m.p. 73–75°C.
Rf =0.45 (6:1, hexane/EtOAc). 1H NMR (300MHz, CDCl3):
δ 1.57 (br s, 1H, NH), 1.95–2.03 (m, 2H, H3), 2.50 (s, 3H,
assistance in isolation of compounds.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
3
SCH3), 2.53 (s, 3H, SCH3), 2.90 (t, J=6.3Hz, 2H, H2),
3.27 (t, 3J=5.4Hz, 2H, H4), 7.15–7.48 (m, 10H). 13C NMR
(75MHz, CDCl3): δ 16.0, 16.4, 22.1, 27.8, 42.3, 122.2,
126.7, 126.9 (2C), 127.1 (2C), 127.4 (2C), 127.5, 129.1,
130.1 (2C), 136.0, 136.1, 137.8, 138.4, 141.1. FTIR (cm−1):
3415, 2950, 2921, 2810, 1599, 1512, 1486, 1433, 1331,
1291, 1252, 1186, 1086, 1012, 961, 886, 813, 750, 721,
532, 507, 474, 439. Anal. calcd for C23H23NS2 (377.13): C,
73.17; H, 6.14; N, 3.71; found: C, 73.24; H, 6.10; N, 3.75.
8-Methoxy-5-(4-(trifluoromethoxy)phenyl)quinoline
(15): Brown solid, yield 73% (0.24g), m.p. 80–82°C.
Rf =0.41 (3:1, hexane/EtOAc). 1H NMR (300MHz, CDCl3):
Funding
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: This
study was supported by grants from the Scientific and
Technological Research Council of Turkey (TUBITAK; project
number: 112T394).
ORCID iD
Salih Ökten
https://orcid.org/0000-0001-9656-1803
3
δ 4.08 (s, 3H, OCH3), 7.06 (d, J=8.4Hz, 1H, H7), 7.28–
3
7.42 (m, 6H), 8.13 (d, J=8.4Hz, 1H, H4), 8.92 (dd,
Supplemental material
4J=1.8Hz, 3J=3.9Hz, 1H). 13C NMR (75MHz, CDCl3): δ
Supplemental material for this article is available online.
56.3, 107.2, 119.0, 121.2 122.0 122.4, 127.7, 130.8, 131.2

Ökten
7
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