Copper(ii) triflate catalyzed three-component reaction for the synthesis of 2,3-diarylquinoline derivatives using aryl amines, aryl aldehydes and styrene oxides

Article abstract of DOI:10.1039/d1ob00125f

An efficient and expedient synthetic protocol is reported for the synthesis of 2,3-diarylquinoline derivatives from readily available aryl amines, aryl aldehydes and styrene oxides using 10 mol% copper(ii) triflate by employing three-component reaction. This approach involves the reaction between thein situgenerated imine (derived from the aryl amine and aryl aldehyde) and styrene oxide, which enables the formation of the desired products. The present method has several advantages such as high atom-economy, high regioselectivity, easy handling, consecutive one C-N and two C-C bond formation, shorter reaction time and broader substrate scope with good yields.

Full text of DOI:10.1039/d1ob00125f

Organic &
Biomolecular Chemistry
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PAPER
Copper(II) triflate catalyzed three-component
reaction for the synthesis of 2,3-diarylquinoline
derivatives using aryl amines, aryl aldehydes and
styrene oxides†
Cite this: Org. Biomol. Chem., 2021,
19, 3255
Saghir Ali
and Abu T. Khan
*
An efficient and expedient synthetic protocol is reported for the synthesis of 2,3-diarylquinoline deriva-
tives from readily available aryl amines, aryl aldehydes and styrene oxides using 10 mol% copper(II) triflate
by employing three-component reaction. This approach involves the reaction between the in situ gener-
ated imine (derived from the aryl amine and aryl aldehyde) and styrene oxide, which enables the formation
of the desired products. The present method has several advantages such as high atom-economy, high
regioselectivity, easy handling, consecutive one C–N and two C–C bond formation, shorter reaction time
and broader substrate scope with good yields.
Received 22nd January 2021,
Accepted 19th March 2021
DOI: 10.1039/d1ob00125f
rsc.li/obc
science.7 Due to their wide applications in diverse fields, the
synthetic community has made tremendous efforts to develop
Introduction
Multicomponent reactions (MCRs) are well-known and well a new method for synthesizing quinoline and its derivatives.
established synthetic approaches, which are extensively Some classical syntheses for obtaining quinolines are
explored in the synthesis of bioactive heterocycles, and combi- Skraup,8a Conrad–Limpach,8b Pfitzinger,8c,d Doebner–Von
natorial and medicinal chemistry.1a These reactions are Miller,8e Friedlaender8f and many other methods.9 To date,
usually one-pot reactions, in which three or more reactants very few methods have been developed for the synthesis of
react sequentially to form a product, where all or most of the 2,3-diarylquinoline derivatives. Recently, Verma et al. reported
atoms incorporate into the structure of the newly formed the synthesis of 2,3-diarylquinoline derivatives by KOH
product.1b–f The notable features of this class of reactions are mediated cycloaddition reaction of o-aminobenzyl alcohols
atom economy, efficiency, diversity, speed and environmen- and internal alkynes (Scheme 1a).10 Similarly, Wu et al.
tally benign nature.2a,b Over the years, the synthetic commu- demonstrated the synthesis of 2,3-diarylquinolines from the
nity has made much effort in designing new MCRs for the con- reaction of substituted aryl amines with two different amino
struction of structurally complex molecules due to numerous acids in the presence of I2 and HI (Scheme 1b).11 Likewise,
advantages.2–4 The quinoline backbone is present in many Reddy et al. showed an approach for the synthesis of 2,3-diaryl-
naturally occurring compounds, namely in the alkaloids. quinoline skeletons using 2-azido phenyl propargylic alcohols
Numerous alkaloids containing the quinoline moiety have and aryl boronic acids in the presence of a Ni(acac)2 catalyst
been marketed as potent drugs.5a In addition to that, related (Scheme 1c).12
natural products are found to exhibit a wide range of biological
activities, such as
Despite the usefulness of the above-mentioned methods,
antimalarial,5b anticancer,5c,d they have some demerits, such as longer reaction time,10
antituberculosis,5e,f and anti-HIV activities.5g Moreover, natu- requirement of expensive starting materials,12 and harsh reac-
rally occurring cinchonidine and quinine are used as chiral tion conditions.10–12 Thus, it is desirable to devise easy and
ligands in asymmetric synthesis.6a–d Furthermore, quinoline economically viable general synthetic methodology to access
and its derivatives have been extensively used in materials the 2,3-diarylquinoline scaffolds. Copper(II) triflate has
emerged as a powerful catalyst in organic synthesis, due to its
stability, low toxicity and easy handling.13a,b In recent years, it
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati-
has been used as an efficient catalyst in promoting several
organic transformations, such as cross-coupling,13c oxidative
781039, Assam, India. E-mail: atk@iitg.ac.in; Fax: +91361 2582349;
Tel: +91 361 2582305
ring closure,13d and aziridination.13e Our research group has
†Electronic supplementary information (ESI) available: CCDC 2040858 (5e). For
demonstrated the synthesis of a variety of quinoline derivatives
ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/
using
a
multi-component
reaction,14a
and
other
d1ob00125f
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Table 1 Optimization of reaction conditionsa,b
Entry
Catalyst
mol%
Solvent
Time
Yield 4a b (%)
1c
2
—
—
—
—
5
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Dioxane
(CH2Cl)2
THF
4 h
4 h
4 h
4 h
2 h
2 h
2 h
2 h
2 h
2 h
2 h
2 h
2 h
2 h
2 h
2 h
NR
NR
NR
31
81
72
36
28
25
30
30
35
26
NR
NR
NR
3c
4
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Bi(OTf)3
Sc(OTf)3
Yb(OTf)3
AgOTf
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
Cu(OTf)2
5
5
6
7
8
10
15
10
10
10
10
10
10
10
10
10
10
9
10
11
12
13
14
15
16
DMF
EtOH
H2O
Scheme 1 Previous methods for the synthesis of 2,3-diarylquinolines
and present work.
a Reaction conditions: All the reactions were performed using p-anisi-
dine (1a, 1.0 mmol), p-tolualdehyde (2a, 1.0 mmol), and styrene oxide
(3a, 1.0 mmol) in solvent (1.0 mL) at 80 °C. b Isolated yield. c Reaction
performed at room temperature. NR (no desired product).
approaches.14b–d We report herein a copper(II) triflate catalyzed
three-component reaction of aryl amines, aryl aldehydes and
styrene oxides, which provides an alternative route to syn-
thesize the 2,3-diarylquinoline skeletons under mild reaction
conditions (Scheme 1d). To the best of our knowledge, copper
(II) triflate catalyzed multicomponent reactions of aryl amines,
aryl aldehydes and styrene oxides are not known so far.
check the efficacy of other catalysts, we screened a similar reac-
tion with different catalysts, such as Bi(OTf)3, Sc(OTf)3, Yb
(OTf)3 and AgOTf (Table 1, entries 7–10). It was noted that
none of them was found to be better than Cu(OTf)2 amongst
various Lewis acids. To find out the solvent effect, the same set
of reactions was run in the presence of 10 mol% of Cu(OTf)2
in different solvents, such as 1,4-dioxane, 1,2-dichloroethane
Results and discussion
To find out the optimum reaction conditions, we have chosen (CH2Cl)2, tetrahydrofuran (THF), N,N-dimethylformamide
p-anisidine (1a, 1.0 mmol), p-tolualdehyde (2a, 1.0 mmol) and (DMF), ethanol (EtOH) and water (H2O). It was observed that
styrene oxide (3a, 1.0 mmol) as the model substrates shown in these solvents gave either low yield or no reaction at all
Table 1. At first, the reactions were carried out without a cata- (Table 1, entries 11–16). In view of the above extensive optimiz-
lyst in DMSO at room temperature as well as heating at 80 °C ation, the best reaction conditions to obtain the desired pro-
(Table 1, entries 1 & 2). No desired product was obtained in ducts are: 10 mol% of Cu(OTf)2 as a catalyst in DMSO solvent
both the cases other than imine formation. Then, a similar and heating at 80 °C.
reaction was performed in the presence of 5 mol% of Cu(OTf)2
After achieving the optimized reaction conditions, we inves-
at room temperature and no reaction took place (Table 1, entry tigated the scope and applicability of the developed method by
3). Interestingly, an identical reaction provided 4a in 31% yield performing the reactions of various substituted anilines (1a–
upon heating at 80 °C (Table 1, entry 4). From the spectral ana- m, 1.0 mmol) with p-tolualdehyde (2a, 1.0 mmol) and styrene
1
lysis of compound 4a by IR, H NMR, 13C NMR and HRMS, it oxide (3a, 1.0 mmol), and successful results are shown in
was found to be 6-methoxy-3-phenyl-2-p-tolylquinoline 4a. Table 2. The reaction occurred smoothly with anilines contain-
Next, we tried to improve the yield of the desired product 4a by ing electron-donating groups at various positions in the aro-
screening the reaction with different parameters such as cata- matic ring. The reaction with anilines having the electron-
lyst loadings, and changing catalysts and solvents. Therefore, donating groups at the para position such as 4-Me and 4-Et
firstly, we tested the effect of loading of the catalyst and we underwent very well and produced the corresponding products
carried out the model reaction in the presence of 10 mol% of 4b and 4c in 78% and 79% yields, respectively. The substituent
Cu(OTf)2 (Table 1, entry 5). It was noted that the reaction pro- methyl group at the 3- and 2-positions of aniline also showed
ceeded faster and it was completed in 2 h. The yield of the very good results; and the reaction underwent quickly to afford
product 4a also improved significantly. When the catalyst the anticipated products 4d and 4e in 76% and 75% yields,
loading was increased from 10 to 15 mol% of Cu(OTf)2, the respectively. Similarly, the reaction of di-substituted anilines,
yield of the product 4a (Table 1, entry 6) decreased. In order to such as 3,4-OMe, 3,4-Me, 3,5-OMe and 3,5-Me, under opti-
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Table 2 The reaction of various substituted anilines 1a–m with
p-tolualdehyde 2a and styrene oxide 3a a,b
p-anisidine (1a, 1.0 mmol) and various benzaldehydes (2,
1.0 mmol) and styrene oxides (3, 1.0 mmol) under the opti-
mized conditions; their successful results are presented in
Table 3. It is noteworthy that electron-donating and electron-
withdrawing substituents present on benzaldehyde were well
tolerated. The reaction of 1a p-anisidine with 2b simple benz-
aldehyde and 3a styrene oxide proceeded well to furnish the
desired product 5a in 81% yield. Similarly, benzaldehydes
having substituents at the p-position, such as 4-OMe, 4-Br,
4-Cl and 4-F, showed good reactivity under optimized con-
ditions, and the reactions proceeded smoothly to provide the
expected products 5b–e in excellent yields. Likewise, 2,4-OMe
and 3,4,5-OMe benzaldehydes upon reaction with p-anisidine
1a and styrene oxide 3a gave the corresponding products 5f
and 5g in 78% and 76% yields, respectively. The 3-Br and 2-F
benzaldehydes were also found to be reactive enough and they
delivered the desired products 5h and 5i in 75% and 79%
yields, respectively. Thereafter, the reaction of 4-Br and 4-Cl
styrene oxides with p-anisidine 1a and p-tolualdehyde 3a suc-
cessfully afforded the expected products 5j and 5k in 77% and
74% yields, respectively.
All the synthesized compounds were characterised by IR,
1H NMR, 13C NMR and HRMS analyses. In addition, the struc-
ture of compound 5e was further established using single
X-ray crystallographic data (see the ESI†).
In order to gain insights into the reaction mechanism, we
performed control experiments (Scheme 2). We carried out the
a Reaction conditions: All the reactions were carried out using substi-
tuted anilines 1a–m (1.0 mmol), p-tolualdehyde 2a (1.0 mmol), styrene
oxide 3a (1.0 mmol), Cu(OTf)2 (10 mol%) and DMSO (1.0 mL) at 80 °C.
b Isolated yield. NR (no desired product).
Table 3 The reaction of p-anisidine 1a with various benzaldehydes
(2b–j) and styrene oxide (3a, 3j & 3k) derivativesa,b
mized conditions provided the expected products 4e–h in
80–77% yields. Gratifyingly, 3,4,5-OMe aniline being sterically
crowded also gave the corresponding quinoline derivative in
76% yield. The fused aniline derivatives, such as 1k 3,4-
(methylenedioxy)-aniline, 1l 5-aminoindane and 1m
1-naphthylamine, showed good reactivity and delivered the
desired structurally complex quinoline derivatives 4k–m in
82–72% yields. We have not observed the formation of other
regio-isomers of compounds of 4d, 4f, 4g, 4k and 4l due to the
steric hindrance of the methyl group at the 3-position of the
aniline moiety as well as more electron density at the para
position with respect to the methyl or OMe group due to the +I
effect.
Unfortunately, the aniline having electron-withdrawing sub-
stituents such as F and NO2 did not provide the corresponding
products 4n and 4o as expected under identical reaction con-
ditions because of less electron density at the ortho-position
with respect to the amine group. In the case of Cl and Br sub-
stituents also, the reaction failed because it enhanced the elec-
tron density at the 4-position due to delocalization of electrons
on halogen atoms rather than increasing at the 2-position with
respect to the amino group.
a Reaction conditions: All the reactions were carried out using p-anisi-
dine 1a (1.0 mmol), benzaldehydes 2b–j (1.0 mmol), styrene oxides 3a,
3i & 3k (1.0 mmol), Cu(OTf)2 (10 mol%), and DMSO (1.0 mL) at 80 °C.
b Isolated yield.
Inspired by the successful results described above, we
extended the scope and generality of this strategy further with
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Conclusion
We have developed an efficient and straightforward novel route
for the synthesis of a wide range of 2,3-diarylquinoline deriva-
tives of biological importance via copper(II) triflate catalyzed
multicomponent reaction using readily available aryl amines,
aryl aldehydes and styrene oxides at 80 °C. The salient features
of this methodology are its cost effective use, high atom
economy, high regioselectivity, convenient use, shorter reac-
tion time, consecutive one C–N and two C–C bond formation
and broad substrate scope with good yield. Further study in
this area is under way in our laboratory.
Scheme 2 Control experiments.
Experimental
General information and methods
Melting points were determined on a melting point apparatus
1
(Buchi-540). H and 13C NMR spectra were recorded on 400 &
600 MHz and 100 & 150 MHz NMR spectrometers (Bruker),
respectively. TMS was used as an internal reference; chemical
shifts (δ scale) are reported in parts per million (ppm). 1H
NMR spectra are reported in the order: multiplicity, coupling
constant (J value) in Hertz (Hz) and no. of protons; signals
were characterized as s (singlet), d (doublet), t (triplet), m
(multiplet) and bs (broad). IR spectra were recorded on an IR
spectrophotometer (PerkinElmer). HRMS spectra were
recorded using a TOF mass analyzer.
General procedure for the synthesis of 2,3-diarylquinoline
derivatives
Scheme 3 The plausible mechanism for the formation of products.
Aryl amine (1, 1.0 mmol), aryl aldehyde (2, 1.0 mmol) and
styrene oxide (3, 1.0 mmol) were taken in dimethyl sulfoxide
first experiment using p-anisidine 1a, p-tolualdehyde 2a and solvent (1.0 mL) in a round-bottomed flask (10 mL). To the
styrene oxide 3a. After stirring the reaction mixture for 2 h, reaction mixture, copper(II) triflate (10 mol%, 36 mg) was
intermediate A (Schiff’s base) was isolated in 89% yield and added. The resulting reaction mixture was kept under stirring
characterized by 1H NMR, 13C NMR and HRMS (Scheme 2a). in an oil-bath at 80 °C. The reaction progress was checked by
Thereafter, we performed another experiment using intermedi- TLC. After the completion of the reaction, the mixture was
ate
A and styrene oxide 3a under standard conditions cooled to room temperature. To extract the product, EtOAc (3 ×
(Scheme 2b). The reaction was completed in 2 h and the 5 mL) was added to the reaction mixture. The combined
expected product 4a was obtained in 79% yield. From this organic layer was washed with water (2 × 5 mL) followed by
observation, the formation of Schiff’s base and its involvement brine solution (5 mL) and dried over anhydrous Na2SO4. The
in the reaction mechanism are confirmed.
solvent was removed in a rotary evaporator and the crude
From the observation of control experiments, the plausible residue was purified using silica gel (60–120 mesh) column
mechanism for the formation of 2,3-diarylquinoline deriva- chromatography.
tives is shown in Scheme 3. At first, aryl amine 1 reacts with
6-Methoxy-3-phenyl-2-p-tolylquinoline (4a). (263 mg, 81%,
aryl aldehyde 2 to give an intermediate A (Schiff’s base),15 yellowish semi-liquid); 1H NMR (400 MHz, CDCl3, Me4Si) δ
which then reacts with styrene oxide 3 to give the intermedi- 8.08 (d, J = 9.2 Hz, 1H), 8.04 (s, 1H), 7.37 (dd, J = 9.2, 2.8 Hz,
ate B, which upon aromatization provides C. The intermedi- 1H), 7.31 (d, J = 8.2 Hz, 2H), 7.26 (m, 5H), 7.11 (d, J = 2.7 Hz,
ate C was detected by mass spectrometry. Elimination of 1H), 7.06 (d, J = 7.9 Hz, 2H), 3.95 (s, 3H), 2.32 (s, 3H); 13C NMR
water from the intermediate C forms D, which undergoes (100 MHz, CDCl3, Me4Si) δ 158.1, 156.1, 143.7, 140.5, 137.8,
6π-electrocyclic ring closure16 to produce intermediate E. The 137.7, 136.6, 134.9, 131.0, 130.1, 129.9, 128.8, 128.4, 128.3,
intermediate E involves a [1, 5] H shift16b to give dihydroqui- 127.2, 122.5, 105.0, 55.8, 21.4; νmax/cm−1 3025 (Ar–H), 2923 (C–
noline F followed by aerial oxidation16b providing the desired H), 1622 (CvC), 1232 (C–O); HRMS (ESI) Calcd for C23H20NO
quinoline 3.
326.1545 (M + H+); Found 326.1571.
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6-Methyl-3-phenyl-2-p-tolylquinoline (4b). (242 mg, 78%, 3029 (Ar–H), 2921 (C–H), 1599 (CvC); HRMS (ESI) Calcd for
1
yellow liquid); H NMR (400 MHz, CDCl3, Me4Si) δ 8.01 (d, J = C24H22N 324.1752 (M + H+); Found 324.1750.
8.6 Hz, 1H), 7.98 (s, 1H), 7.53 (s, 1H), 7.48 (d, J = 8.6 Hz, 1H),
5,7-Dimethoxy-3-phenyl-2-p-tolylquinoline (4h). (281 mg,
7.25 (d, J = 8.1 Hz, 2H), 7.23–7.17 (m, 5H), 6.99 (d, J = 7.9 Hz, 79%, brown semi-solid); 1H NMR (400 MHz, CDCl3, Me4Si) δ
2H), 2.48 (s, 3H), 2.25 (s, 3H); 13C NMR (100 MHz, CDCl3, 8.35 (s, 1H), 7.25 (d, J = 8.1 Hz, 2H), 7.21–7.13 (m, 5H), 7.05 (s,
Me4Si) δ 157.7, 146.1, 140.5, 137.9, 137.7, 137.2, 136.7, 134.7, 1H), 6.98 (d, J = 7.9 Hz, 2H), 6.44 (s, 1H), 3.89 (s, 3H), 3.87 (s,
132.1, 130.1, 129.9, 129.2, 128.8, 128.4, 127.4, 127.2, 126.4, 3H), 2.24 (s, 3H); 13C NMR (100 MHz, CDCl3, Me4Si) δ 161.6,
21.9, 21.5; νmax/cm−1 3027 (Ar–H), 2924 (C–H), 1600 (CvC); 158.9, 156.2, 149.5, 140.8, 137.9, 137.8, 132.8, 131.6, 130.1,
HRMS (ESI) Calcd for C23H20N 310.1596 (M + H+); Found 130.0, 128.8, 128.3, 126.9, 115.8, 99.8, 98.3, 55.9, 55.9, 21.4;
310.1589.
νmax/cm−1 3018 (Ar–H), 2928 (C–H), 1620 (CvC), 1211 (C–O);
6-Ethyl-3-phenyl-2-p-tolylquinoline (4c). (255 mg, 79%, dark HRMS (ESI) Calcd for C24H22NO2 356.1651 (M + H+); Found
1
brown liquid); H NMR (400 MHz, CDCl3, Me4Si) δ 8.02 (d, J = 356.1637.
8.6 Hz, 1H), 7.98 (s, 1H), 7.52 (s, 1H), 7.49 (d, J = 8.6 Hz, 1H),
5,7-Dimethyl-3-phenyl-2-p-tolylquinoline (4i). (250 mg 77%,
7.24 (d, J = 8.1 Hz, 2H), 7.18 (ddd, J = 13.9, 6.5, 3.3 Hz, 5H), yellow solid); mp 111–113 °C; 1H NMR (400 MHz, CDCl3,
6.97 (d, J = 7.9 Hz, 2H), 2.75 (q, J = 7.6 Hz, 2H), 2.22 (s, 3H), Me4Si) δ 8.15 (s, 1H), 7.76 (s, 1H), 7.26 (d, J = 8.1 Hz, 2H),
1.25 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3, Me4Si) δ 7.24–7.18 (m, 5H), 7.14 (s, 1H), 6.99 (d, J = 7.9 Hz, 2H), 2.59 (s,
157.7, 146.3, 142.9, 140.6, 137.8, 137.8, 137.3, 134.6, 131.0, 3H), 2.45 (s, 3H), 2.24 (s, 3H); 13C NMR (100 MHz, CDCl3,
130.1, 129.9, 129.9, 129.3, 128.8, 128.3, 127.2, 125.1, 76.9, 29.1, Me4Si) δ 157.9, 148.1, 140.9, 139.7, 137.9, 137.8, 134.3, 134.2,
21.4, 15.6; νmax/cm−1 3032 (Ar–H), 2964 (C–H), 1600 (CvC); 133.4, 130.2, 130.0, 129.6, 128.8, 128.4, 127.2, 126.7, 124.7,
HRMS (ESI) Calcd for C24H22N 324.1752 (M + H+); Found 22.1, 21.4, 18.7; νmax/cm−1 3032 (Ar–H), 2922 (C–H), 1601
324.1775.
(CvC); HRMS (ESI) Calcd for C24H22N 324.1752 (M + H+);
7-Methyl-3-phenyl-2-p-tolylquinoline (4d). (234 mg, 76%, Found 324.1752.
yellow liquid); 1H NMR (400 MHz, CDCl3, Me4Si) δ 8.09 (s, 1H),
5,6,7-Trimethoxy-3-phenyl-2-p-tolylquinoline (4j). (281 mg,
7.97 (s, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.38 (d, J = 8.3 Hz, 1H), 76%, brown semi-solid); 1H NMR (400 MHz, CDCl3, Me4Si) δ
7.33 (d, J = 8.0 Hz, 2H), 7.32–7.24 (m, 5H), 7.07 (d, J = 8.1 Hz, 8.24 (s, 1H), 7.27 (s, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.17–7.13 (m,
2H), 2.58 (s, 3H), 2.32 (s, 3H); 13C NMR (100 MHz, CDCl3, 5H), 6.95 (d, J = 7.9 Hz, 2H), 3.97 (s, 3H), 3.91 (s, 3H), 3.89 (s,
Me4Si) δ 158.5, 147.7, 140.6, 140.0, 137.9, 137.9, 137.5, 133.9, 3H), 2.20 (s, 3H); 13C NMR (150 MHz, CDCl3, Me4Si) δ 157.7,
130.1, 129.9, 129.1, 128.8, 128.6, 128.4, 127.3, 127.2, 125.4, 156.1, 146.9, 145.1, 140.9, 140.6, 137.7, 137.7, 132.3, 132.1,
22.1, 21.5; νmax/cm−1 3034 (Ar–H), 2922 (C–H), 1601 (CvC); 129.9, 129.9, 128.7, 128.2, 126.9, 118.2, 104.2, 61.7, 61.3, 56.2,
HRMS (ESI) Calcd for C23H20N 310.1596 (M + H+); Found 21.3; νmax/cm−1 3024 (Ar–H), 2935 (C–H), 1610 (CvC), 1225
310.1620.
8-Methyl-3-phenyl-2-p-tolylquinoline (4e). (232 mg, 75%, Found 386.1750.
(C–O); HRMS (ESI) Calcd for C25H24NO3 386.1756 (M + H+);
1
greenish liquid); H NMR (400 MHz, CDCl3, Me4Si) δ 8.10 (s,
7-Phenyl-6-p-tolyl-[1,3]dioxolo[4,5-g]quinoline (4k). (278 mg,
1H), 7.69 (d, J = 8.0 Hz, 1H), 7.57 (d, J = 6.9 Hz, 1H), 7.46–7.40 82%, dark brown semi-solid); 1H NMR (400 MHz, CDCl3,
(m, 3H), 7.36–7.28 (m, 5H), 7.08 (d, J = 7.9 Hz, 2H), 2.88 (s, Me4Si) δ 7.86 (s, 1H), 7.40 (s, 1H), 7.22 (d, J = 8.1 Hz, 2H),
3H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3, Me4Si) δ 156.74, 7.21–7.12 (m, 5H), 6.98 (d, J = 9.8 Hz, 3H), 6.02 (s, 2H), 2.23 (s,
146.5, 140.8, 138.0, 138.0, 137.6, 134.2, 130.5, 130.1, 129.9, 3H); 13C NMR (150 MHz, CDCl3, Me4Si) δ 156.1, 150.9, 148.1,
129.71, 128.7, 128.5, 127.2, 127.2, 126.5, 125.5, 21.5, 18.1; νmax
/
145.6, 140.4, 137.7, 137.6, 136.8, 132.9, 130.0, 129.9, 128.8,
cm−1 3034 (Ar–H), 2919 (C–H), 1600 (CvC); HRMS (ESI) Calcd 128.4, 127.1, 124.2, 105.9, 102.5, 101.8, 21.4; νmax/cm−1 3032
for C23H20N 310.1596 (M + H+); Found 310.1620.
(Ar–H), 2913 (C–H), 1611 (CvC), 1220 (C–O); HRMS (ESI)
6,7-Dimethoxy-3-phenyl-2-p-tolylquinoline (4f). (285 mg, Calcd for C23H18NO2 340.1338 (M + H+); Found 386.1365.
1
80%, white solid); mp 120–122 °C; H NMR (400 MHz, CDCl3,
3-Phenyl-2-p-tolyl-7,8-dihydro-6H-cyclopenta[g]quinoline
Me4Si) δ 7.90 (s, 1H), 7.45 (s, 1H), 7.22 (d, J = 8.0 Hz, 2H), (4l). (255 mg, 76%, yellow solid); mp 110–112 °C; 1H NMR
7.20–7.14 (m, 5H), 6.98 (d, J = 9.8 Hz, 3H), 3.96 (s, 3H), 3.93 (s, (400 MHz, CDCl3, Me4Si) δ 7.97 (s, 1H), 7.92 (s, 1H), 7.55 (s,
3H), 2.23 (s, 3H); 13C NMR (100 MHz, CDCl3, Me4Si) δ 156.2, 1H), 7.25 (d, J = 8.1 Hz, 2H), 7.22–7.17 (m, 5H), 6.99 (d, J = 7.9
152.9, 150.2, 144.3, 140.6, 137.7, 136.3, 132.9, 130.1, 129.9, Hz, 2H), 3.07–2.98 (m, 4H), 2.24 (s, 3H), 2.10 (quint, J = 7.4 Hz,
128.8, 128.3, 127.1, 122.9, 108.1, 104.9, 56.4, 56.3, 21.4; νmax
/
2H); 13C NMR (100 MHz, CDCl3, Me4Si) δ 157.3, 148.0, 147.3,
cm−1 3012 (Ar–H), 2924 (C–H), 1619 (CvC), 1231 (C–O); HRMS 144.5, 140.7, 137.7, 137.4, 133.6, 130.1, 129.9, 128.8, 128.4,
(ESI) Calcd for C24H22NO2 356.1651 (M + H+); Found 356.1650. 128.3, 127.1, 126.5, 123.7, 121.5, 33.2, 32.7, 26.4, 21.4; νmax
/
6,7-Dimethyl-3-phenyl-2-p-tolylquinoline (4g). (252 mg, 78%, cm−1 3029 (Ar–H), 2948 (C–H), 1599 (CvC); HRMS (ESI) Calcd
yellowish semi-solid); 1H NMR (400 MHz, CDCl3, Me4Si) δ 7.95 for C25H22N 336.1752 (M + H+); Found 336.1752.
(s, 1H), 7.90 (s, 1H), 7.51 (s, 1H), 7.25 (d, J = 8.1 Hz, 2H),
3-Phenyl-2-p-tolylbenzo[h]quinoline (4m). (249 mg, 72%,
7.22–7.16 (m, 5H), 6.99 (d, J = 7.9 Hz, 2H), 2.42 (s, 3H), 2.39 (s, white solid); mp = 140–143 °C; 1H NMR (400 MHz, CDCl3,
3H), 2.25 (s, 3H); 13C NMR (100 MHz, CDCl3, Me4Si) δ 157.5, Me4Si) δ 8.16 (s, 1H), 7.92 (d, J = 7.1 Hz, 1H), 7.82 (d, J = 8.8
146.6, 140.7, 140.1, 137.8, 136.9, 136.8, 133.9, 130.2, 129.9, Hz, 1H), 7.74–7.69 (m, 3H), 7.51 (d, J = 8.1 Hz, 2H), 7.34 (s,
128.8, 128.4, 127.1, 126.8, 126.0, 21.5, 20.7, 20.3; νmax/cm−1 4H), 7.12 (d, J = 7.9 Hz, 2H), 2.37 (s, 3H); 13C NMR (100 MHz,
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CDCl3, Me4Si) δ 156.3, 145.5, 140.7, 138.0, 137.9, 134.9, 133.9,
2-(3,4-Dimethoxyphenyl)-6-methoxy-3-phenylquinoline (5f).
1
131.8, 130.6, 129.9, 128.8, 128.5, 128.3, 127.9, 127.6, 127.3, (292 mg, 78%, dark brown liquid); H NMR (400 MHz, CDCl3,
127.1, 125.2, 125.2, 125.1, 21.5; νmax/cm−1 3041 (Ar–H), 2923 Me4Si) δ 8.08 (d, J = 9.2 Hz, 1H), 8.04 (s, 1H), 7.38 (dd, J = 9.2,
(C–H), 1590 (CvC); HRMS (ESI) Calcd for C26H20N 346.1596 2.8 Hz, 1H), 7.29 (dt, J = 7.2, 4.8 Hz, 5H), 7.11 (dd, J = 8.1, 2.2
(M + H+); Found 346.1609.
Hz, 2H), 6.89 (d, J = 2.0 Hz, 1H), 6.80 (d, J = 8.3 Hz, 1H), 3.96
6-Methoxy-2,3-diphenylquinoline (5a). (311 mg, 81%, dark (s, 3H), 3.87 (s, 3H), 3.61 (s, 3H); 13C NMR (100 MHz, CDCl3,
solid); mp 123–125 °C; 1H NMR (400 MHz, CDCl3, Me4Si) δ Me4Si) δ 158.1, 155.6, 149.1, 148.3, 143.7, 140.8, 136.7, 134.9,
8.10 (d, J = 9.2 Hz, 1H), 8.06 (s, 1H), 7.43–7.37 (m, 3H), 133.2, 131.0, 129.9, 128.5, 128.2, 127.3, 123.0, 122.5, 113.8,
7.28–7.25 (m, 8H), 7.12 (d, J = 2.7 Hz, 1H), 3.95 (s, 3H); 13C 110.9, 105.1, 56.1, 55.8, 55.8; νmax/cm−1 3011 (Ar–H), 2929 (C–
NMR (100 MHz, CDCl3, Me4Si) δ 158.2, 156.1, 143.6, 140.7, H), 1623 (CvC), 1233 (C–O); HRMS (ESI) Calcd for C24H22NO3
140.3, 136.6, 134.9, 131.1, 130.2, 129.9, 128.4, 128.4, 128.1, 372.1600 (M + H+); Found 372.1627.
127.9, 127.3, 122.6, 105.1, 55.8; νmax/cm−1 3059 (Ar–H), 2834
6-Methoxy-3-phenyl-2-(3,4,5-trimethoxyphenyl)quinoline
(C–H), 1623 (CvC), 1233 (C–O); HRMS (ESI) Calcd for (5g). (308 mg, 76%, dark brown liquid); 1H NMR (400 MHz,
C22H18NO 312.1388 (M + H+); Found 312.1411.
CDCl3, Me4Si) δ 8.17 (d, J = 9.0 Hz, 1H), 8.09 (s, 1H), 7.41 (dd, J
6-Methoxy-2-(4-methoxyphenyl)-3-phenylquinoline
(5b). = 9.2, 2.8 Hz, 1H), 7.35–7.27 (m, 5H), 7.13 (d, J = 2.7 Hz, 1H),
(274 mg, 80%, brown liquid); 1H NMR (400 MHz, CDCl3, 6.68 (s, 2H), 3.96 (s, 3H), 3.82 (s, 3H), 3.64 (s, 6H); 13C NMR
Me4Si) δ 8.06 (d, J = 9.2 Hz, 1H), 7.97 (s, 1H), 7.31 (dd, J = 8.9, (100 MHz, CDCl3, Me4Si) δ 158.4, 155.44, 152.9, 140.649, 138.7,
4.0 Hz, 3H), 7.23 (t, J = 5.0 Hz, 3H), 7.18 (t, J = 3.8 Hz, 2H), 137.0, 135.0, 130.7, 129.8, 128.6, 128.4, 127.4, 122.93, 115.1,
7.04 (d, J = 2.7 Hz, 1H), 6.72 (d, J = 8.7 Hz, 2H), 3.88 (s, 3H), 115.0, 108.0, 105.1, 65.4, 61.1, 56.1, 55.83; νmax/cm−1 3014 (Ar–
3.72 (s, 3H); 13C NMR (100 MHz, CDCl3, Me4Si) δ 159.8, H), 2934 (C–H), 1590 (CvC), 1241 (C–O); HRMS (ESI) Calcd for
158.2, 155.5, 143.2, 140.4, 137.1, 134.9, 131.7, 130.6, 129.9, C25H24NO4 402.1705 (M + H+); Found 402.1749.
129.5, 128.5, 128.3, 127.4, 122.7, 113.6, 105.1, 55.8, 55.4; νmax
/
2-(3-Bromophenyl)-6-methoxy-3-phenylquinoline
(5h).
cm−1 3018 (Ar–H), 2929 (C–H), 1619 (CvC), 1232 (C–O); (293 mg, 75%, brown liquid); 1H NMR (400 MHz, CDCl3,
HRMS (ESI) Calcd for C23H20NO2 342.1494 (M + H+); Found Me4Si) δ 8.02 (s, 1H), 7.64 (s, 1H), 7.35 (dd, J = 9.1, 2.9 Hz, 2H),
342.1542.
7.27–7.23 (m, 3H), 7.19–7.15 (m, 4H), 7.06 (d, J = 2.7 Hz, 1H),
2-(4-Bromophenyl)-6-methoxy-3-phenylquinoline
(5c). 7.01 (t, J = 7.9 Hz, 1H), 3.89 (s, 3H); 13C NMR (100 MHz,
(296 mg, 76%, brown solid); mp 142–144 °C; 1H NMR CDCl3, Me4Si) δ 158.6, 154.2, 143.4, 139.7, 137.0, 134.9, 133.2,
(400 MHz, CDCl3, Me4Si) δ 8.07 (d, J = 8.8 Hz, 2H), 7.40 (dd, J = 131.1, 130.9, 129.9, 129.4, 129.0, 128.7, 128.6, 127.7, 123.1,
8.8, 2.3 Hz, 3H), 7.33–7.30 (m, 5H), 7.23 (dd, J = 6.6, 3.0 Hz, 122.4, 105.0, 55.8; νmax/cm−1 3066 (Ar–H), 2929 (C–H), 1622
2H), 7.12 (d, J = 2.8 Hz, 1H), 3.96 (s, 3H); 13C NMR (100 MHz, (CvC), 1245 (C–O); HRMS (ESI) Calcd for C22H17BrNO
CDCl3, Me4Si) δ 158.4, 154.7, 143.7, 140.0, 139.6, 136.8, 134.8, 390.0494 (M + H+); Found 390.0510.
131.9, 131.3, 131.1, 129.9, 128.6, 128.5, 127.6, 122.8, 122.5,
2-(2-Fluorophenyl)-6-methoxy-3-phenylquinoline
(5i).
1
105.0, 55.8; νmax/cm−1 3021 (Ar–H), 2925 (C–H), 1622 (CvC), (260 mg, 79%, black solid); mp 84–86 °C; H NMR (400 MHz,
1233 (C–O); HRMS (ESI) Calcd for C22H17BrNO 390.0494 (M + CDCl3, Me4Si) δ 8.05 (d, J = 9.3 Hz, 1H), 8.02 (s, 1H), 7.46 (td, J
H+); Found 390.0483.
= 7.4, 1.8 Hz, 1H), 7.33 (dd, J = 9.2, 2.8 Hz, 1H), 7.23–7.14 (m,
2-(4-Chlorophenyl)-6-methoxy-3-phenylquinoline
(5d). 6H), 7.11 (dd, J = 7.5, 1.0 Hz, 1H), 7.08 (t, J = 2.7 Hz, 1H), 6.80
(266 mg, 77%, brown solid); mp 148–150 °C; 1H NMR (t, J = 8.7 Hz, 1H), 3.88 (s, 3H); 13C NMR (100 MHz, CDCl3,
1
(400 MHz, CDCl3, Me4Si) δ 8.07 (d, J = 8.9 Hz, 2H), 7.41–7.38 Me4Si) δ 159.9 (d, JC–F = 247 Hz), 158.5, 151.8, 143.3, 139.6,
(m, 1H), 7.38–7.36 (m, 2H), 7.32 (dd, J = 5.0, 1.8 Hz, 3H), 139.6, 136.2, 135.9, 131.9 (d, 3JC–F = 3 Hz), 130.9, 130.3 (d, 3JC–F
7.26–7.22 (m, 4H), 7.12 (d, J = 2.7 Hz, 1H), 3.96 (s, 3H); 13C = 8 Hz), 129.3, 128.9, 128.2, 127.4, 124.4 (d, JC–F = 3 Hz),
3
NMR (100 MHz, CDCl3, Me4Si) δ 158.4, 154.7, 143.7, 140.0, 122.8, 115.7 (d, 2JC–F = 21 Hz), 105.1, 55.8; νmax/cm−1 3028 (Ar–
139.2, 136.8, 134.8, 134.1, 131.6, 131.0, 129.9, 128.6, 128.5, H), 2920 (C–H), 1622 (CvC), 1232 (C–O); HRMS (ESI) Calcd for
128.3, 127.5, 122.8, 104.9, 55.8; νmax/cm−1 3025 (Ar–H), 2926 C22H17FNO 330.1294 (M + H+); Found 330.1322.
(C–H), 1623 (CvC), 1232 (C–O); HRMS (ESI) Calcd for
3-(4-Bromophenyl)-6-methoxy-2-p-tolylquinoline
(312 mg, 77%, brown liquid); 1H NMR (400 MHz, CDCl3,
(5e). Me4Si) δ 8.07 (d, J = 9.2 Hz, 1H), 8.01 (s, 1H), 7.42 (d, J = 8.4
(5j).
C22H17ClNO 346.0999 (M + H+); Found 346.1026.
2-(4-Fluorophenyl)-6-methoxy-3-phenylquinoline
1
(266 mg, 80%, brown solid); mp 95–97 °C; H NMR (400 MHz, Hz, 2H), 7.39 (dd, J = 9.2, 2.8 Hz, 1H), 7.30 (d, J = 8.1 Hz, 2H),
CDCl3, Me4Si) δ 8.07 (d, J = 9.9 Hz, 2H), 7.43–7.37 (m, 3H), 7.31 7.15–7.06 (m, 5H), 3.95 (s, 3H), 2.34 (s, 3H); 13C NMR
(dd, J = 5.0, 1.8 Hz, 3H), 7.23 (dd, J = 6.6, 3.1 Hz, 2H), 7.12 (d, J (100 MHz, CDCl3, Me4Si) δ 158.2, 155.8, 143.8, 139.5, 137.9,
= 2.8 Hz, 1H), 6.95 (t, J = 8.8 Hz, 2H), 3.96 (s, 3H); 13C NMR 137.5, 136.5, 133.7, 131.8, 131.6, 131.5, 131.1, 130.0, 129.0,
1
(100 MHz, CDCl3, Me4Si) δ 162.8 (d, JC–F = 246 Hz), 158.3, 122.8, 121.6, 104.9, 55.8, 21.5; νmax/cm−1 3022 (Ar–H), 2924 (C–
155.0, 143.7, 140.2, 136.7 (d, 3JC–F = 5 Hz), 134.8, 132.1, 131.98, H), 1620 (CvC), 1241 (C–O); HRMS (ESI) Calcd for
131.0, 129.9, 128.5, 128.4, 127.5, 122.7, 115.1 (2JC–F = 21 Hz), C23H19BrNO 404.0650 (M + H+); Found 404.0670.
105.0, 55.82; νmax/cm−1 3022 (Ar–H), 2926 (C–H), 1623 (CvC),
3-(4-Chlorophenyl)-6-methoxy-2-p-tolylquinoline
(5k).
1230 (C–O); HRMS (ESI) Calcd for C22H17FNO 330.1294 (M + (281 mg, 78%, brown liquid); 1H NMR (400 MHz, CDCl3,
H+); Found 330.1321.
Me4Si) δ 8.08 (d, J = 9.2 Hz, 1H), 8.01 (s, 1H), 7.39 (dd, J = 9.2,
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2.7 Hz, 1H), 7.28 (dd, J = 9.9, 8.6 Hz, 4H), 7.21–7.15 (m, 2H),
7.10 (dd, J = 8.0, 5.4 Hz, 3H), 3.95 (s, 3H), 2.34 (s, 3H); 13C
NMR (100 MHz, CDCl3, Me4Si) δ 158.2, 155.9, 143.8, 139.0,
137.9, 137.5, 136.5, 133.7, 133.4, 131.2, 131.1, 130.0, 129.0,
128.6, 128.2, 122.8, 104.9, 55.8, 21.5; νmax/cm−1 3014 (Ar–H),
2929 (C–H), 1623 (CvC), 1222 (C–O); HRMS (ESI) Calcd for
C23H19ClNO 360.1155 (M + H+); Found 360.1167.
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1
(200 mg, 89%, gray solid); H NMR (400 MHz, CDCl3, Me4Si) δ
8.42 (s, 1H), 7.76 (d, J = 8.1 Hz, 2H), 7.28–7.19 (m, 4H), 6.91 (d,
J = 8.9 Hz, 2H), 3.80 (s, 3H), 2.39 (s, 3H); 13C NMR (100 MHz,
CDCl3, Me4Si) δ 158.59, 158.31, 145.29, 141.60, 134.08, 129.63,
128.76, 122.32, 114.54, 77.55, 77.23, 76.91, 55.63, 21.74; HRMS
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Conflicts of interest
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24, 6806–6808; (b) X. Zhang, A. S. Shetty and S. A. Jenekhe,
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There are no conflicts to declare.
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Acknowledgements
SA is grateful to IIT Guwahati for providing a fellowship. CIF,
IIT Guwahati is highly acknowledged for instrument facilities.
We are also grateful to the Department of Science and
Technology, New Delhi for financial support (Research grant
no.: CRG/2018/002120/OC) to Professor A. T. Khan. We are also
thankful to MHRD for the 400 MHz NMR facility.
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