Iodine monobromide catalysed regioselective synthesis of 3-arylquinolines from α-aminoacetophenones and: Trans -β-nitrostyrenes

Article abstract of DOI:10.1039/c8ob02333f

A simple and efficient method for regioselective synthesis of 3-arylquinolines is described from α-aminoacetophenones and trans-β-nitrostyrenes using 20 mol% iodine monobromide as a catalyst in acetonitrile solvent at 80 °C. The present method involves tandem reaction of α-aminoacetophenones and trans-β-nitrostyrenes, formation of two new C-C bonds and cleavage of one C-C bond in a single step. The salient features of the protocol are metal- and oxidant-free reaction conditions, broad substrate scope, and good yields.

Full text of DOI:10.1039/c8ob02333f

Organic &
Biomolecular Chemistry
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PAPER
Iodine monobromide catalysed regioselective
synthesis of 3-arylquinolines from α-amino-
acetophenones and trans-β-nitrostyrenes†
Cite this: Org. Biomol. Chem., 2019,
17, 347
Radhakrishna Gattu,
Santa Mondal,
Saghir Ali
and Abu T. Khan
*
A simple and efficient method for regioselective synthesis of 3-arylquinolines is described from
α-aminoacetophenones and trans-β-nitrostyrenes using 20 mol% iodine monobromide as a catalyst in
acetonitrile solvent at 80 °C. The present method involves tandem reaction of α-aminoacetophenones
and trans-β-nitrostyrenes, formation of two new C–C bonds and cleavage of one C–C bond in a single
step. The salient features of the protocol are metal- and oxidant-free reaction conditions, broad substrate
scope, and good yields.
Received 20th September 2018,
Accepted 4th December 2018
DOI: 10.1039/c8ob02333f
rsc.li/obc
(Scheme 1b).15 Despite the advantages of the reported
methods for producing 3-arylquinolines, there are certain
Introduction
Quinoline and its basic skeleton are widely distributed in natu- limitations such as a small substrate scope and non-avail-
rally occurring alkaloids1 and pharmaceuticals.2 These quino- ability of substituted styrene epoxide,14 phenylacetaldehyde15
line based compounds play a vital role in medicinal chemistry and alkenyl iodide11 derivatives at the commercial scale. The
due to various biological properties, such as antimalarial,3
antimicrobial,4a anti-inflammatory,4b anthelmintic,4c anti-
HIV-1 5 and analgesic activities. In addition, optically active
quinolines are used in asymmetric synthesis6 as catalysts and
some of them are used as functional materials and metal com-
plexes7a for organic light-emitting diodes (OLEDs)7b in
materials chemisty.8 Due to wide biological activities and
various useful applications, a new synthetic route to synthesize
different quinoline derivatives has drawn great attention
among synthetic chemists. 3-Arylquinolines are an important
class of compounds having biological activities.9 Various
methods have been reported for the synthesis of 3-arylquino-
lines such as the palladium catalyzed C3-arylation of quino-
lines through C–H functionalization,10 Ullmann coupling11 of
ortho-acylanilines and alkenyliodides, [4 + 2] hetero Diels–
Alder (HDA)12 reaction of 2-aminobenzyl alcohols with term-
inal alkynes, and Friedlander-type reaction13 of ortho-amino-
benzaldehydes
with
3-oxa-2,3-diaryl-propionaldehydes.
Recently, Wang et al. reported 3-arylquinolines by the FeCl3
promoted tandem reaction of anilines and styrene epoxides14
(Scheme 1a). Similarly, 3-arylquinolines were also developed
from anilines and aldehydes through C–H functionalization
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781
039, India. E-mail: atk@iitg.ac.in; Fax: +91 361 2582349; Tel: +91 361 2582305
†Electronic supplementary information (ESI) available. CCDC 1835007 for com-
pound 3h. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c8ob02333f
Scheme 1 Synthetic strategies for the formation of arylquinolines and
our previous approach.
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Table 1 Optimization of reaction conditionsa,b,c,d
requirement of pre-functionalized anilines like ortho-amino-
benzylalcohol13 and ortho-aminobenzaldehyde11,13,20c deriva-
tives is also another limitation. Therefore, a new method for
producing 3-arylquinolines from simple starting materials is
always highly desirable to synthetic chemists.
However, Mancheño,16 Wang17 and Huo18 et al. reported
the reaction of peptides/glycine derivatives with alkenes for
the formation of 4-arylquinoline derivatives (Scheme 1c).
Recently, we have reported that the reaction of N-alkylanilines
and trans-β-nitrostyrenes resulted in the formation of 3-aryl-
indole derivatives (Scheme 1d).19 After seeing the notable work
of Huo18 and others,16,17 we anticipated that by replacing
N-alkylanilines with α-amino-acetophenones upon reaction
with trans-β-nitrostyrenes these might provide either 4-aryl-
quinolines or 3-arylquinolines. The literature reveals that
Entry
Catalyst
Mol%
Solvent
Time (h)
Yield (%)
1
—
IBr
IBr
NBS
CBr4
ICl
Iodine
IBr
IBr
IBr
—
10
10
10
10
10
10
20
30
20
20
20
20
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
MeOH
DMSO
THF
24
12
14
24
24
24
24
10
08
24
24
24
14
NR
NR
62
12
34
Trace
NR
72
2c
3
4
5
6
7
8
9
66
10
NR
NR
NR
40
trans-β-nitrostyrenes20 are one of the important precursors for 11
IBr
IBr
IBr
12d
13d
the synthesis of five and six membered heterocyclic rings.
Iodine monobromide21 is also found to be well explored in
organic synthesis. Herein, we report an alternative method for
the regioselective synthesis of 3-arylquinolines through a
tandem reaction22 of α-aminoacetophenones and trans-
β-nitrostyrenes in acetonitrile at 80 °C using 20 mol% iodine
monobromide as a catalyst (Scheme 1e).
DCE
a All the reactions were performed using 1-phenyl-2-(p-tolylamino)
ethanone 1a (1.0 mmol) and (E)-1-methyl-4-(2-nitrovinyl)benzene 2a
(1.0 mmol) at 80 °C. b Isolated yield. c Reaction performed at room
temperature. d Reaction performed at 50 °C. NR = no reaction.
cular iodine under identical conditions (Table 1, entries 6
and 7). Furthermore, in order to improve the yield, the reaction
was also examined with 20 mol% of IBr and it was noted that
Results and discussion
For the present study, various α-aminoacetophenone23 deriva- the reaction was completed within 10 h instead of 14 h. At the
tives (1a–l) and trans-β-nitrostyrenes24 (2a–n) were prepared by same time the yield was improved from 62% to 72% (Table 1,
following the reported literature procedures. To find suitable entry 8). It is important to mention that there is no further
reaction conditions, 1-phenyl-2-(phenylamino)ethanones (1a) increase in yield by increasing the amount of IBr from 20% to
and (E)-1-methyl-4-(2-nitrovinyl)benzene (2a) were chosen as 30 mol% (Table 1, entry 9). The reaction was unsuccessful
the model substrates. Initially the reaction was examined when it was screened with other solvents such as MeOH,
without any catalyst in CH3CN at 80 °C. It did not give any DMSO and THF (Table 1, entries 10–12). Notably, it gave only
desired product and the starting material was recovered 40% yield in dichloroethane (DCE) (Table 1, entry 13).
(Table 1, entry 1). The same reaction was carried out with Summing up, the best optimized reaction conditions are
10 mol% of IBr in CH3CN at room temperature, which was 20 mol% of IBr in acetonitrile at 80 °C.
also unsuccessful (Table 1, entry 2). Subsequently, the reaction
With the optimized reaction conditions, the substrate scope
mixture was heated at 80 °C and it resulted in the formation of was studied with various substituents on the arene ring of the
product 3a in 62% yield (Table 1, entry 3). The structure of aniline moiety 1 with trans-β-nitrostyrenes 2a and 2b as rep-
1
compound 3a was established through IR, H NMR, 13C NMR resented in Table 2. It is worth mentioning that the substrates
spectra and HRMS.
having electron donating groups 4-Me, 4-Et, 4-OMe, 3-Me, and
1H NMR shows only nine aromatic protons and two singlets 3,4-di-Me and electron withdrawing groups 4-F and 4-Cl on
at δ 2.56 and 2.44 for two methyl groups. In addition, no car- 1-phenyl-2-(phenylamino)ethanone provided the desired pro-
bonyl carbon signal was present in the 13C spectrum, which ducts 3a–h in 58–72% yields.
clearly indicates the elimination of the benzoyl group.
Similarly, there were no absorption peaks for the CO group (at executed
To further extend our synthetic protocol, the reaction was
with 2-(benzo[d][1,3]dioxol-5-ylamino)-1-phenyl-
1650–1700 cm−1) and the NO2 group (at 1350 cm−1 and ethanone 1i, 2-((2,3-dihydro-1H-inden-5-yl)amino)-1-phenyl-
1550 cm−1) in the IR spectrum. This clearly shows the elimin- ethanone 1j and 2-(naphthalen-1-ylamino)-1-phenylethanone 1k
ation of both the benzoyl group and –NO2 group during the with (E)-1-methyl-4-(2-nitrovinyl)benzene 2a and it resulted in
course of the reaction.
the formation of the expected products 3i–3k in 56% and 70%
On screening the identical set of reactions with other cata- yields. The reaction of 2-((9H-fluoren-2-yl)amino)-1-phenyl-
lysts like N-bromosuccinimide (NBS) and tetrabromomethane ethanone 1l and (E)-1-methyl-4-(2-nitrovinyl)benzene 2a gave
(CBr4), the yield was found to be 12% and 34%, respectively exclusively the 3l regioisomer. The ortho-substituted Me and
(Table 1, entries 4 and 5). Furthermore, it was observed that OMe aniline derivatives were unsuccessful which may be due
the reaction failed with iodine monochloride (ICl) and mole- to steric hindrance. The reaction with electron withdrawing
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Table 2 Substrate scope of various substituted anilines with trans-
β-nitrostyrenesa,b
Table 3 Reaction of 1-phenyl-2-(p-tolylamino)ethanone with various
trans-β-nitrostyrenesa,b
a The reactions were carried out using substituted anilines 1a–l
(1 mmol), trans-β-nitrostyrenes 2 (1 mmol), CH3CN (1 mL) and IBr
(20 mol%) at 80 °C. b Isolated yield.
a The reactions were carried out using 1-phenyl-2-(p-tolylamino)etha-
none 1a (1 mmol), trans-β-nitrostyrenes 2b–m (1 mmol), CH3CN
(2 mL) and IBr (20 mol%) at 80 °C. b Isolated yield.
groups such as 4-Br and 4-NO2 substituents on aniline deriva-
tives also failed to obtain the desired products.
To generalize the present protocol, the substrate scope was
further verified with 1-phenyl-2-(p-tolylamino)ethanone 1a and
various substituted trans-β-nitrostyrenes 2b–i under optimized
reaction conditions and the desired products 3m–3t were
obtained in 54–70% yields as shown in Table 3. The electron
donating groups 4-OMe, 4-OH and 3,4,5-tri-OMe groups
worked well. Electron withdrawing group(s) on the aromatic
ring of trans-β-nitrostyrenes such as 4-F, 4-Cl, 4-Br, and 3-Br
were also well tolerated. The reaction proceeded well even with
a heterocyclic nitrostyrene such as (E)-2-(2-nitrovinyl)thio-
phene 2j to give the product 3u in 62% yield. In addition,
(E)-2-(2-nitrovinyl)naphthalene 2k was also successful to give
the product 3v in 66% yield.
Scheme 2 Reaction of a glycine derivative with trans-β-nitrostyrene.
β-nitrostyrene 2a in the presence of 20 mol% iodine monobro-
mide catalyst under identical reaction conditions.
Unfortunately, we did not obtain the expected 3-arylquinoline
product as shown in Scheme 3. From this observation, it was
seen that the carbonyl group adjacent to the phenyl group
plays a crucial role in this particular transformation.
Strong electron withdrawing groups such as the 4-NO2 sub-
stituent on the phenyl ring of trans-β-nitrostyrene 2l failed to
provide the desired product 3w. The reaction with (E)-(1-nitro-
prop-1-en-2-yl)benzene 2m failed to give compound 3x due to
steric hindrance of the methyl substituent at the β-position of
trans-β-nitrostyrene.
Scheme 3 Reaction of 4-methyl-N-phenethylaniline with trans-
β-nitrostyrene.
We have also examined the reaction of ethyl 2-(p-tolylamino)
acetate 1m (1 mmol) with (E)-1-methyl-4-(2-nitrovinyl)benzene 2a
To examine the large scale reaction, we have executed the
(1 mmol) under identical reaction conditions, but we did not reaction of 1-phenyl-2-(p-tolylamino)ethanone 1a (10 mmol)
obtain the expected product 3a as shown in Scheme 2. and (E)-1-ethyl-4-(2-nitrovinyl)benzene 2n (10 mmol) under
To further verify the substrate scope, we have performed a similar reaction conditions and it gave the product 3y in 62%
reaction of 4-methyl-N-phenethylaniline 1n with trans- yield as shown in Scheme 4.
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phenones and trans-β-nitrostyrenes. The advantages of the
present protocol are the formation of two new C–C bonds,
metal and oxidant free reaction conditions, broad substrate
scope and good yields. In addition, the protocol is also useful
for the synthesis of 3-heteroaryl quinolines.
Scheme 4 Gram scale reaction.
All the synthesized compounds were well characterized by
IR, 1H NMR, 13C NMR spectra and HRMS. In addition, the
Experimental
structure of compound 3s was confirmed through single X-ray General information and methods
crystallographic data (see the ESI†) (Fig. 1).
Melting points were determined on a melting point apparatus
and are uncorrected. 1H and 13C NMR spectra were recorded
on 400 & 600 MHz and 100 & 150 MHz NMR spectrometers.
TMS was used as the internal reference and chemical shifts
(δ scale) are reported in parts per million (ppm). 1H NMR
spectra are reported in the following order: multiplicity, coup-
ling 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. HRMS spectra were recorded using an ESI
and APCI (TOF) mode. The X-ray crystal structures were deter-
mined using a single XRD diffractometer.
Fig. 1 The ORTEP diagram of 3s with 40% ellipsoid probability (CCDC
no. 1835007†).
General procedure for synthesis of 3-arylquinolines (3a–3y)
A
mixture α-aminoacetophenone 1a (1.0 mmol), trans-
β-nitrostyrene 2a (1.0 mmol) and IBr (20 mol%) was taken in a
dry 25 mL round bottomed flask in 5 mL of acetonitrile. The
reaction mixture was stirred in a heated oil-bath at 80 °C. The
progress of the reaction was monitored by TLC. After com-
pletion of the reaction, acetonitrile was removed in a rotary
evaporator under reduced pressure and the crude residue was
then extracted with dichloromethane (2 × 25 mL). The com-
bined organic layer was washed with 25 mL of 10% sodium
thiosulfate solution to remove iodine, washed with water and
it was dried over anhydrous sodium sulfate. After the removal
of organic solvent in a rotary evaporator, the crude residue was
purified through silica gel (60–120 mesh) column chromato-
graphy and the desired product 3a was obtained in 72% yield.
The desired product was eluted with a mixture of ethyl acetate
and petroleum ether (05 : 95). A similar procedure was followed
for all other substrates.
Scheme 5 Plausible reaction mechanism for the formation of
3-arylquinolines.
The plausible mechanism for the formation of 3-arylquino-
lines is depicted in Scheme 5. Initially, 1-phenyl-2-(p-tolyl-
amino)ethanone 1a transforms to intermediate B in the pres-
ence of IBr, which reacts with trans-β-nitrostyrene 2a to form an
intermediate C through the formation of a new C–C bond. The
intermediate C undergoes ortho-cyclisation with the arene ring
of the aniline to form tetrahydroquinoline E, which transforms
to dihydroquinoline F, which subsequently undergoes aromati-
sation through elimination of the aldehyde group to form a
stable 3-arylquinoline 3a. The formation of intermediate com-
pound C was confirmed by HRMS analysis (see the ESI†).
6-Methyl-3-(p-tolyl)quinoline (3a). Yield 72% (168 mg), col-
ourless liquid, 1H NMR (600 MHz, CDCl3): δ 9.10 (d, J = 2.3 Hz,
1H), 8.22–8.17 (m, 1H), 8.03 (d, J = 8.5 Hz, 1H), 7.64–7.62 (m,
1H), 7.62–7.59 (m, 2H), 7.54 (dd, J = 8.6, 1.9 Hz, 1H), 7.35–7.31
(m, 2H), 2.56 (d, J = 1.0 Hz, 3H), 2.44 (s, 3H); 13C NMR
(150 MHz, CDCl3): δ 149.1, 145.8, 138.2, 137.1, 135.2, 133.9,
132.6, 131.8, 130.1, 128.8, 128.3, 127.4, 126.9, 21.9, 21.4; IR
(KBr) νmax 2928, 2972, 1632, 1421, 1084, 1024, 814 cm−1; HRMS
(ESI) calcd for C17H16N 234.1277 (M + H+); found 234.1299.
6-Ethyl-3-phenylquinoline (3b). Yield 65% (152 mg), color-
1
less liquid, H NMR (600 MHz, CDCl3): δ 9.12 (d, J = 2.3 Hz,
Conclusions
1H), 8.25 (d, J = 2.3 Hz, 1H), 8.06 (d, J = 8.6 Hz, 1H), 7.73–7.70
In summary, we have developed a new protocol for the regio- (m, 2H), 7.66 (d, J = 1.9 Hz, 1H), 7.60 (dd, J = 8.6, 2.0 Hz, 1H),
selective synthesis of 3-arylquinolines through the iodine 7.54–7.51 (m, 2H), 7.45–7.43 (m, 1H), 2.90–2.83 (m, 2H), 1.36
monobromide catalyzed tandem reaction of α-aminoaceto- (t, J = 7.6 Hz, 3H); 13C NMR (150 MHz, CDCl3): δ 149.2, 146.24,
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143.4, 138.2, 134.0, 133.1, 130.9, 129.4, 129.1, 128.3, 128.2, 3H), 2.43 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 149.1, 146.4,
127.6, 125.7, 29.1, 15.6; IR (KBr) νmax 3033, 2964, 2927, 2954, 139.8, 138.0, 137.1, 135.5, 133.2, 132.2, 130.0, 128.5, 127.6,
1676, 1494, 1261, 834 cm−1; HRMS (ESI) calcd for C17H16N 127.4, 127.3, 126.9, 21.4, 20.7, 20.3; IR (KBr) νmax 2928, 2974,
234.1277 (M + H+); found 234.1266.
1624, 1414, 1084, 832 cm−1; HRMS (ESI) calcd for C18H18N
6-Methoxy-3-phenylquinoline (3c). Yield 68% (160 mg), 248.1434 (M + H+); found 248.1457.
white solid, mp 118–119 °C, 1H NMR (600 MHz, CDCl3): δ 9.03
7-(p-Tolyl)-[1,3]dioxolo[4,5-g]quinoline (3i). Yield 66%
1
(d, J = 2.2 Hz, 1H), 8.22 (d, J = 2.2 Hz, 1H), 8.05 (d, J = 9.1 Hz, (173 mg), yellow liquid, H NMR (600 MHz, CDCl3): δ 8.94 (d,
1H), 7.74–7.68 (m, 2H), 7.53 (t, J = 7.7 Hz, 2H), 7.45–7.42 (m, J = 2.3 Hz, 1H), 8.10 (d, J = 2.3 Hz, 1H), 7.57 (d, J = 8.1 Hz, 2H),
1H), 7.38 (dd, J = 9.2, 2.8 Hz, 1H), 7.14 (d, J = 2.8 Hz, 1H), 3.96 7.41 (s, 1H), 7.31 (d, J = 7.9 Hz, 2H), 7.10 (s, 1H), 6.12 (s, 2H),
(s, 3H); 13C NMR (150 MHz, CDCl3): δ 158.4, 147.4, 143.4, 2.42 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 150.8, 148.4, 147.4,
138.2, 134.4, 132.6, 130.5, 129.4, 129.3, 128.3, 127.6, 122.6, 138.0, 135.2, 132.6, 132.4, 130.0, 128.4, 127.2, 125.4, 105.6,
105.5, 55.80; IR (KBr) νmax 2964, 2862, 2781, 1609, 1517, 103.0, 101.9, 21.4; IR (KBr) νmax 2921, 2851, 1642, 1466, 1025,
1258, 1026, 832 cm−1; HRMS (ESI) calcd for C16H14NO 993 cm−1; HRMS (ESI) calcd for C17H14NO2 264.1019 (M + H+);
236.1070 (M + H+); found 236.1092.
found 264.1024.
6-Fluoro-3-(p-tolyl)quinoline (3d). Yield 62% (147 mg), light
3-(p-Tolyl)-7,8-dihydro-6H-cyclopenta[g]quinoline (3j). Yield
yellow color liquid, H NMR (600 MHz, CDCl3): δ 9.15 (d, J = 70% (181 mg), yellow liquid, 1H NMR (600 MHz, CDCl3): δ 9.08
2.2 Hz, 1H), 8.25 (d, J = 2.2 Hz, 1H), 8.17–8.12 (m, 1H), (d, J = 2.3 Hz, 1H), 8.21 (d, J = 2.3 Hz, 1H), 7.93 (s, 1H), 7.68 (s,
7.65–7.62 (m, 2H), 7.51 (dd, J = 8.6, 2.3 Hz, 2H), 7.37 (d, J = 1H), 7.63 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 7.8 Hz, 2H), 3.15 (td,
7.8 Hz, 2H), 2.46 (s, 3H); 13C NMR (150 MHz, CDCl3): δ 161.8, J = 7.4, 1.3 Hz, 2H), 3.13–3.07 (m, 2H), 2.45 (s, 3H), 2.23–2.18
160.1, 149.4, 144.4, 138.6, 134.7, 134.7, 132.5, 132.4, 131.8, (m, 2H); 13C NMR (150 MHz, CDCl3): δ 148.8, 147.8, 147.1,
131.8, 130.2, 127.5, 119.8, 119.6, 111.1, 110.9, 21.4; IR (KBr) 144.6, 137.9, 135.5, 132.9, 132.7, 130.0, 127.5, 127.3, 123.5,
νmax 3062, 2928, 2846, 1654, 1348, 1228, 1098, 1024, 924, 122.1, 33.1, 32.7, 26.4, 21.4; IR (KBr) νmax 2920, 1648, 1468,
828 cm−1; HRMS (ESI) calcd for C16H13FN 238.1027 (M + H+); 1260, 1084, 924, 860 cm−1; HRMS (ESI) calcd for C19H18N
1
found 238.1042.
260.1434 (M + H+); found 260.1438.
6-Chloro-3-phenylquinoline (3e). Yield 58% (139 mg), light
3-(p-Tolyl)benzo[h]quinoline (3k). Yield 56% (151 mg),
brown colour solid, mp 106–108 °C, 1H NMR (400 MHz, colorless liquid, 1H NMR (600 MHz, CDCl3) δ 9.31 (d, J =
CDCl3): δ 9.17 (d, J = 2.3 Hz, 1H), 8.22 (d, J = 2.2 Hz, 1H), 8.09 8.1 Hz, 1H), 9.27 (d, J = 2.3 Hz, 1H), 8.35 (d, J = 2.3 Hz, 1H),
(d, J = 8.9 Hz, 1H), 7.87 (d, J = 2.3 Hz, 1H), 7.73–7.69 (m, 2H), 7.95 (d, J = 7.8 Hz, 1H), 7.87 (d, J = 8.8 Hz, 1H), 7.77 (d, J =
7.66 (dd, J = 9.0, 2.3 Hz, 1H), 7.54 (dd, J = 8.3, 6.7 Hz, 2H), 8.6 Hz, 2H), 7.74–7.71 (m, 1H), 7.69 (d, J = 8.0 Hz, 2H), 7.38 (d,
7.48–7.44 (m, 1H); 13C NMR (150 MHz, CDCl3): δ 150.3, 145.8, J = 7.9 Hz, 2H), 2.47 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 148.1,
137.6, 134.9, 133.0, 132.5, 130.9, 130.6, 129.5, 128.9, 128.7, 145.5, 138.3, 135.2, 134.7, 133.7, 133.3, 131.6, 130.1, 128.4, 128.3,
127.7, 126.8; IR (KBr) νmax 3054, 2928, 2852, 1608, 1512, 1098, 128.1, 127.4, 127.4, 126.5, 125.7, 124.5, 21.4; IR (KBr) νmax 2916,
1034, 828 cm−1; HRMS (ESI) calcd for C15H11ClN 240.0575 2850, 1735, 1656, 1458, 1046, 799 cm−1; HRMS (ESI) calcd for
(M + H+); found 240.0597.
C20H16N 270.1277 (M + H+); found 270.1294.
7-Methyl-3-(p-tolyl)quinoline (3f). Yield 66% (154 mg),
2-(p-Tolyl)-11H-indeno[2,1-f]quinoline (3l). Yield 62%
colorless liquid, 1H NMR (600 MHz, CDCl3): δ 9.15 (s, 1H), (190 mg), light yellow semi solid, H NMR (600 MHz, CDCl3)
8.26 (d, J = 2.2 Hz, 1H), 7.92 (s, 1H), 7.79 (d, J = 8.3 Hz, 1H), δ 9.15 (d, J = 2.3 Hz, 1H), 8.42 (d, J = 2.2 Hz, 1H), 8.26 (s, 1H),
7.65–7.60 (m, 2H), 7.43 (dd, J = 8.3, 1.6 Hz, 1H), 7.37–7.32 (m, 8.21 (s, 1H), 7.96 (d, J = 7.5 Hz, 1H), 7.65 (d, J = 7.9 Hz, 2H),
2H), 2.61 (s, 3H), 2.46 (s, 3H); 13C NMR (150 MHz, CDCl3): 7.61 (d, J = 7.4 Hz, 1H), 7.45 (t, J = 7.4 Hz, 1H), 7.41 (td, J = 7.4,
δ 150.1, 147.6, 139.8, 138.1, 135.3, 132.8, 130.1, 130.1, 129.4, 1.1 Hz, 1H), 7.36 (d, J = 7.8 Hz, 2H), 4.18 (s, 2H), 2.45 (s, 3H);
128.3, 127.8, 127.6, 127.4, 22.2, 21.4; IR (KBr) νmax 2921, 2978, 13C NMR (151 MHz, CDCl3) δ 148.7, 145.7, 144.2, 141.9, 140.4,
1628, 1411, 1092, 817 cm−1; HRMS (ESI) calcd for C17H16N 138.3, 135.1, 133.8, 133.6, 130.2, 129.1, 128.4, 127.9, 127.4,
1
234.1277 (M + H+); found 234.1287.
127.4, 125.7, 124.4, 121.1, 117.6, 36.9, 21.4; IR (KBr) νmax 2918,
7-Chloro-3-(p-tolyl)quinoline (3g). Yield 64% (162 mg), 2850, 1731, 1645, 1467, 1045, 721 cm−1; HRMS (ESI) calcd for
colorless liquid, 1H NMR (600 MHz, CDCl3) δ 9.19 (d, J = C23H18N 308.1434 (M + H+); found 308.1459.
2.3 Hz, 1H), 8.28 (d, J = 2.4 Hz, 1H), 8.15 (d, J = 2.1 Hz, 1H),
6-Methyl-3-phenylquinoline (3m). Yield 70% (154 mg), white
1
7.84 (d, J = 8.7 Hz, 1H), 7.64–7.61 (m, 2H), 7.55 (dd, J = 8.7, solid, mp 61–62 °C, H NMR (400 MHz, CDCl3): δ 9.11 (d, J =
2.1 Hz, 1H), 7.38–7.35 (m, 2H), 2.46 (s, 3H); 13C NMR 2.2 Hz, 1H), 8.22 (d, J = 2.2 Hz, 1H), 8.03 (d, J = 8.6 Hz, 1H),
(151 MHz, CDCl3) δ 151.1, 147.6, 138.6, 135.1, 134.7, 134.2, 7.73–7.69 (m, 2H), 7.66–7.64 (m, 1H), 7.56 (d, J = 8.8 Hz, 1H),
132.8, 130.3, 130.2, 129.4, 128.4, 128.3, 127.4, 126.7, 21.4; IR 7.54–7.51 (m, 2H), 7.44 (t, J = 6.7 Hz, 1H), 2.57 (s, 3H); 13C NMR
(KBr) νmax 2916, 2850, 1729, 1469, 1180, 1046, 817 cm−1; HRMS (150 MHz, CDCl3): δ 149.2, 146.2, 138.3, 137.1, 134.0, 132.9,
(ESI) calcd for C16H13ClN 254.0731 (M + H+); found 254.0752.
131.9, 129.4, 129.1, 128.2, 127.6, 127.0, 21.9; IR (KBr) νmax 3054,
6,7-Dimethyl-3-(p-tolyl)quinoline (3h). Yield 68% (168 mg), 2927, 2824, 1644, 1514, 1324, 1236, 1214, 1042, 922 cm−1; HRMS
1
yellow liquid, H NMR (600 MHz, CDCl3): δ 9.07 (d, J = 2.2 Hz, (ESI) calcd for C16H14N 220.1121 (M + H+); found 220.1141.
1H), 8.17 (d, J = 2.3 Hz, 1H), 7.88 (s, 1H), 7.61 (d, J = 1.7 Hz,
3-(4-Methoxyphenyl)-6-methylquinoline (3n). Yield 68%
2H), 7.59 (s, 1H), 7.32 (d, J = 7.9 Hz, 2H), 2.49 (s, 3H), 2.46 (s, (170 mg), yellow solid, 136–137 °C, 1H NMR (600 MHz, CDCl3):
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δ 9.09 (d, J = 2.2 Hz, 1H), 8.17 (d, J = 2.3 Hz, 1H), 8.02 (d, J = (d, J = 2.3 Hz, 1H), 8.20 (d, J = 2.2 Hz, 1H), 8.04 (d, J = 8.6 Hz,
8.6 Hz, 1H), 7.66–7.63 (m, 2H), 7.62 (s, 1H), 7.53 (dd, J = 8.6, 1H), 7.84 (t, J = 1.9 Hz, 1H), 7.64 (s, 1H), 7.63 (dt, J = 7.7,
2.0 Hz, 1H), 7.07–7.03 (m, 2H), 3.88 (s, 3H), 2.56 (s, 3H); 13C NMR 1.3 Hz, 1H), 7.57 (td, J = 8.3, 7.9, 1.6 Hz, 2H), 7.39 (t, J = 7.8 Hz,
(150 MHz, CDCl3): δ 159.9, 149.0, 145.6, 137.1, 133.7, 133.2, 131.7, 1H), 2.57 (s, 3H); 13C NMR (151 MHz, CDCl3) δ 148.6, 146.2,
130.6, 128.8, 128.7, 126.9, 114.8, 55.6, 21.9; IR (KBr) νmax 2922, 140.3, 137.4, 133.2, 132.6, 132.4, 131.2, 130.9, 130.6, 128.9,
2851, 1716, 1607, 1514, 1251, 1028, 830 cm−1; HRMS (ESI) calcd 128.1, 127.1, 126.2, 123.4, 21.9; IR (KBr) νmax 2924, 2858, 1648,
for C17H16NO 250.1226 (M + H+); found 250.1248.
4-(6-Methylquinolin-3-yl)phenol (3o). Yield 58% (136 mg), 298.0226 (M + H+); found 298.0251 and 300.0232.
light yellow liquid, 1H NMR (600 MHz, CDCl3): δ 9.07 (d, J =
6-Methyl-3-(thiophen-2-yl)quinoline (3u).
1482, 1072, 821 cm−1; HRMS (ESI) calcd for C16H13BrN
Yield
62%
1
2.3 Hz, 1H), 8.16 (d, J = 2.3 Hz, 1H), 8.01 (d, J = 8.6 Hz, 1H), (140 mg), colorless liquid, H NMR (400 MHz, CDCl3): δ 9.13
7.62 (s, 1H), 7.62–7.58 (m, 2H), 7.53 (dd, J = 8.6, 2.0 Hz, 1H), (d, J = 2.3 Hz, 1H), 8.19 (d, J = 2.3 Hz, 1H), 7.99 (d, J = 8.6 Hz,
7.00 (d, J = 8.6 Hz, 2H), 2.56 (s, 3H); 13C NMR (400 MHz, 1H), 7.60 (d, J = 1.7 Hz, 1H), 7.52 (dd, J = 8.6, 2.0 Hz, 1H), 7.49
CDCl3): δ 156.1, 149.0, 145.7, 137.1, 133.6, 132.1, 131.7, 130.8, (dd, J = 3.6, 1.1 Hz, 1H), 7.39 (dd, J = 5.1, 1.2 Hz, 1H), 7.17 (dd,
128.9, 128.9, 128.4, 126.9, 116.3, 21.9; IR (KBr) νmax 2927, J = 5.1, 3.6 Hz, 1H), 2.55 (s, 3H); δ 13C NMR (101 MHz, CDCl3)
2857, 1749, 1637, 1514, 1076, 834 cm−1; HRMS (ESI) calcd for δ 147.9, 146.1, 141.2, 137.4, 131.9, 131.1, 129.1, 128.6, 128.2,
C16H14NO 236.1070 (M + H+); found 236.1091.
127.8, 126.8, 126.2, 124.5, 21.8; IR (KBr) νmax 2932, 2858, 1648,
6-Methyl-3-(3,4,5-trimethoxyphenyl)quinoline (3p). Yield 1466, 1068, 832 cm−1; HRMS (ESI) calcd for C14H12NS
1
62% (192 mg), yellow color liquid, H NMR (600 MHz, CDCl3): 226.0685 (M + H+); found 226.0709.
δ 9.07 (d, J = 2.1 Hz, 1H), 8.18 (d, J = 2.2 Hz, 1H), 8.04 (d, J =
6-Methyl-3-(naphthalen-2-yl)quinoline (3v). Yield 66%
1
8.6 Hz, 1H), 7.66 (s, 1H), 7.56 (dd, J = 8.6, 1.9 Hz, 1H), 6.88 (s, (178 mg), white semisolid, H NMR (600 MHz, CDCl3) δ 9.25
2H), 3.97 (s, 6H), 3.92 (s, 3H), 2.57 (s, 3H); 13C NMR (100 MHz, (d, J = 2.3 Hz, 1H), 8.36 (d, J = 2.2 Hz, 1H), 8.19–8.16 (m, 1H),
CDCl3): δ 154.0, 149.1, 146.1, 138.5, 137.2, 134.2, 134.1, 132.7, 8.06 (d, J = 8.5 Hz, 1H), 8.00 (d, J = 8.5 Hz, 1H), 7.98–7.94 (m,
131.9, 129.0, 128.2, 126.9, 104.9, 61.2, 56.5, 21.9; IR (KBr) νmax 1H), 7.91 (dd, J = 7.4, 1.7 Hz, 1H), 7.85 (dd, J = 8.5, 1.9 Hz, 1H),
2926, 2854, 1720, 1612, 1521, 1248, 1022, 824 cm−1; HRMS 7.69 (s, 1H), 7.58 (dd, J = 8.4, 1.9 Hz, 1H), 7.55 (td, J = 7.1,
(ESI) calcd for C19H20NO3 310.1438 (M + H+); found 310.1452.
1.6 Hz, 2H), 2.61–2.52 (m, 3H); 13C NMR (151 MHz, CDCl3)
3-(4-Fluorophenyl)-6-methylquinoline (3q). Yield 60% δ 149.3, 145.9, 137.3, 135.5, 133.9, 133.8, 133.3, 133.1, 132.1,
1
(142 mg), white semi solid, H NMR (400 MHz, CDCl3): δ 9.05 129.2, 128.9, 128.5, 128.4, 127.9, 127.1, 126.9, 126.7, 126.6,
(d, J = 2.3 Hz, 1H), 8.19 (d, J = 2.3 Hz, 1H), 8.02 (d, J = 8.6 Hz, 125.5, 21.9; IR (KBr) νmax 2932, 2868, 1656, 1472, 1068,
1H), 7.65–7.60 (m, 3H), 7.56 (dd, J = 8.5, 1.9 Hz, 1H), 7.51–7.47 832 cm−1; HRMS (ESI) calcd for C20H16N 270.1277 (M + H+);
(m, 2H), 2.57 (s, 3H); 13C NMR (600 MHz, CDCl3): δ 163.9, found 270.1300.
162.3, 148.9, 146.1, 137.3, 134.4, 134.4, 133.1, 132.7, 132.1,
3-(4-Ethylphenyl)-6-methylquinoline (3y). Yield 62% (1.54 g),
1
129.8, 129.3, 129.2, 129.0, 128.2, 126.9, 116.4, 116.3, 21.9; IR brown liquid, H NMR (600 MHz, CDCl3) δ 9.11 (d, J = 2.3 Hz,
(KBr) νmax 3061, 2924, 2855, 1653, 1600, 1231, 1099, 1037, 917, 1H), 8.19 (d, J = 2.3 Hz, 1H), 8.02 (d, J = 8.6 Hz, 1H), 7.66–7.61
831 cm−1; HRMS (ESI) calcd for C16H13FN 238.1027 (M + H+); (m, 3H), 7.54 (dd, J = 8.6, 1.9 Hz, 1H), 7.36 (d, J = 7.9 Hz, 2H),
found 238.1018.
2.73 (q, J = 7.6 Hz, 2H), 2.56 (s, 3H), 1.30 (t, J = 7.6 Hz, 3H); 13
C
3-(4-Chlorophenyl)-6-methylquinoline (3r). Yield 56% NMR (151 MHz, CDCl3) δ 149.2, 145.9, 144.5, 137.0, 135.5,
(142 mg), brown color solid, mp 150–151 °C, 1H NMR 133.9, 132.5, 131.8, 131.7, 128.9, 128.9, 128.3, 127.5, 126.9,
(400 MHz, CDCl3): δ 9.05 (d, J = 2.3 Hz, 1H), 8.19 (d, J = 2.3 Hz, 28.8, 21.9, 15.8; IR (KBr) νmax 3025, 2964, 2828, 1499, 1345,
1H), 8.02 (d, J = 8.6 Hz, 1H), 7.65–7.60 (m, 3H), 7.56 (dd, J = 1019, 833 cm−1; HRMS (ESI) calcd for C18H18N 248.1434
8.5, 1.9 Hz, 1H), 7.51–7.47 (m, 2H), 2.57 (s, 3H); 13C NMR (M + H+); found 248.1459.
(600 MHz, CDCl3): δ 148.7, 146.2, 137.4, 136.7, 134.5, 132.9,
132.8, 132.2, 129.6, 129.5, 128.9, 128.8, 128.2, 127.0, 21.8; IR
(KBr) νmax 3024, 2922, 2852, 1607, 1513, 1252, 1090, 1026, Conflicts of interest
829 cm−1; HRMS (ESI) calcd for C16H13ClN 254.0731 (M + H+);
There are no conflicts to declare.
found 254.0749.
3-(4-Bromophenyl)-6-methylquinoline (3s). Yield 54%
(160 mg), white solid, mp 180–181 °C, 1H NMR (400 MHz,
CDCl3): δ 9.06 (d, J = 2.3 Hz, 1H), 8.19 (dd, J = 2.3, 0.8 Hz, 1H),
Acknowledgements
8.03 (d, J = 8.6 Hz, 1H), 7.67–7.64 (m, 1H), 7.64 (d, J = 2.0 Hz, 2H),
RG, SM and SA are thankful to IIT Guwahati for their research
fellowship. We are thankful to CIF, IIT Guwahati.
7.58–7.57 (m, 2H), 7.56 (d, J = 1.9 Hz, 1H), 2.56 (s, 3H); 13C NMR
(600 MHz, CDCl3): δ 148.6, 146.1, 137.4, 137.1, 132.9, 132.5, 132.3,
129.1, 128.9, 128.2, 127.0, 122.7, 21.9; IR (KBr) νmax 2921, 2854,
1651, 1484, 1078, 825 cm−1; HRMS (ESI) calcd for C16H13BrN
Notes and references
298.0226 (M + H+); found 298.0245 and 300.0236.
3-(3-Bromophenyl)-6-methylquinoline (3t). Yield 58%
(174 mg), white semi solid, H NMR (600 MHz, CDCl3) δ 9.06
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