NH4I-mediated sp3 C-H cross-dehydrogenative coupling of benzylamines with 2-methylquinoline for the synthesis of E-2-styrylquinolines

Article abstract of DOI:10.1177/17475198211019253

Without any metal catalyst, a simple and efficient method for the synthesis of E-2-styrylquinolines through sp³ C-H cross-dehydrogenative coupling of benzylamines with 2-methylquinolines mediated by NH₄I under air is successfully developed. The oxidative olefination proceeded through deamination and sp³ C–H bond activation. A plausible mechanism is proposed for the construction of E-2-styrylquinolines.

Full text of DOI:10.1177/17475198211019253

1019253CHL0010.1177/17475198211019253Journal of Chemical ResearchLi et al.
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Research Paper
Journal of Chemical Research
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NH4I-mediated sp3 C-H cross-dehydrogenative
coupling of benzylamines with 2-methylquinoline
for the synthesis of E-2-styrylquinolines
https://doi.org/10.1177/17475198211019253
DOI: 10.1177/17475198211019253
journals.sagepub.com/home/chl
Xue Li1 , Bin Huang1, JiangWei Wang2,
YuanYuan Zhang1 and WeiBo Liao1
Abstract
Without any metal catalyst, a simple and efficient method for the synthesis of E-2-styrylquinolines through sp3 C-H cross-
dehydrogenative coupling of benzylamines with 2-methylquinolines mediated by NH4I under air is successfully developed.
The oxidative olefination proceeded through deamination and sp3 C–H bond activation. A plausible mechanism is
proposed for the construction of E-2-styrylquinolines.
Keywords
2-methylquinolines, benzylamines, E-2-styrylquinolines, NH4I, sp3 C-H cross-dehydrogenative coupling
Date received: 4 March 2021; accepted: 4 May 2021
2-methylquinolines and aldehydes under the synergistic
Introduction
organocatalysis of 1,3-dimethylbarbituric acid/HOAc for
On account of their unique structures and reactivities, qui-
24 h. In 2020, Susanta et al.9 reported that E-2-
noline and its derivatives are widely utilized to prepare
styrylquinolines could be prepared from 2-methylquino-
lines by reactions with primary alcohols or primary amines
various biologically important compounds.1,2 Among qui-
noline derivatives, E-2-styrylquinolines are typical bioac-
using the NaCl/TBHP oxidative system. In the same year,
tive compounds acting as potent HIV-1 integrase
Zhang et al.10 showed that reactions of 2-methylquinolines
inhibitors,3–5 leukotriene receptor antagonists,6,7 and
and primary alcohols catalyzed by MnO2 in the presence of
antiallergic drugs.8 The wide applications of E-2-
styrylquinolines have attracted considerable attention in
synthetic chemistry. In the past 10 years, widely used
methods for the synthesis of E-2-styrylquinolines have
KOH eliminated molecule of H2O and were transformed
into E-2-styrylquinolines. Nevertheless, these methods suf-
fer from environmental and economic concerns as they
mainly involved the reactions of 2-methylquinolines with
benzyl alcohols,9–12 benzyl amines,9,13–15 aldehydes,16–19
and
1Drug Research Center, Traditional Chinese Medicine Institute of
N-benzylidene-4-methylbenzenesulfonamides20
Jiangxi, Nanchang, P.R. China
(Scheme 1). In 2011, Qian et al.20 disclosed that Fe(OAc)2
promoted the reactions of 2-methylquinolines and
N-benzylidene-4-methylbenzenesulfonamides by remov-
ing a molecule of p-toluenesulfonamide to give E-2-
styrylquinolines. In 2019, Liang et al.16 reported that
various 2-alkenylquinolines could be produced from
2Jiangxi Provincial Hospital of Traditional Chinese medicine, Nanchang,
P.R. China
Corresponding author:
Xue Li, Drug Research Center, Traditional Chinese Medicine Institute
of Jiangxi, Nanchang 330046, P.R. China.
Email: m18702635626@163.com
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Journal of Chemical Research
Scheme 1. Methods for the preparation of E-2-styrylquinolines.
Table 1. Optimization of the reaction conditions for the
synthesis of 3a.a
utilize strong oxidants and transition-metal catalysts, which
impede the applicability of these methods. To avoid these
drawbacks, we successfully developed a method that
involves deamination and sp3 C-H cross-dehydrogenative
coupling of 2-methylquinolines and benzylamines to give
various E-2-styrylquinolines mediated by NH4I in moder-
ate to good yields (30%–93%) with NMP (N-methyl-2-
pyrrolidone) as the solvent, without any other metal catalyst
at 160°C for 10h (Scheme 1).
Entry
Additive
Solvent
Temp (°C)
Yield of 3a (%)b
1
2
3
4
5
6
7
8
NBS
NIS
TBAI
NH4I
KI
None
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NH4I
NMP
NMP
NMP
NMP
NMP
NMP
CH3CN
Toluene
DMSO
NMP
NMP
NMP
NMP
NMP
NMP
NMP
120
120
120
120
120
160
80
110
160
140
160
160
160
160
160
160
Trace
Trace
10
52
Trace
0
Trace
Trace
Trace
64
85
85
Results and discussion
The 2-Methylquinoline (1a) and benzylamine (2a) were
selected as model substrates to optimize the reaction condi-
tions for the synthesis of E-2-styrylquinoline (3a). The
effects of different catalysts, solvents, and temperatures
were investigated. The results are summarized in Table 1.
First,differentadditivessuchasNBS(N-bromosuccinimide),
NIS (N-iodosuccinimide), TBAI (tetra-n-butylammonium
iodide), NH4I, and KI were investigated and NH4I was
found to be the best, affording a 52% yield of 3a (Table 1,
entries 1–5). No product was formed in the absence of a
catalyst, even on increasing the reaction temperature to
160°C (Table 1, entry 6). Next, the solvent was optimized
and NMP was found to be the best (Table 1, entries 4 and
7–9). With NMP as the solvent, the reaction temperature
and time were further optimized. When the temperature
was increased from 120–160°C, the yield of 3a increased
from 52% to 85% (Table 1, entries 4, 10, and 11), which
indicated that the reaction proceeded best at 160°C. To fur-
ther improve the yield of 3a, increased reaction times of up
to 24h at 160°C were tested; however, the yield was not
9
10
11
12c
13d
14e
15f
16g
86
85
18
86
NBS: N-bromosuccinimide; NIS: N-iodosuccinimide; TBAI: tetra-n-
butylammonium iodide; DMSO: dimethyl sulfoxide.
aReaction conditions: 1a (1.0mmol), 2a (3.0mmol), catalyst (1.2 equiv),
solvent (4mL), in air, 10h.
bIsolated yield.
cReaction time: 14h.
dReaction time: 18h.
eReaction time: 24h.
fUnder N2.
gUnder O2.

Li et al.
3
Table 2. Substrate scope of various quinolines having sp3 carbons in the oxidative cross-dehydrogenative coupling reaction.a
Entry
R
Productb
Yield (%)c
1
2
3
4
5
6
7
8
(1a) H
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
85
73
80
61
68
82
93
89
83
90
87
54
59
60
(1b) 3-CH3
(1c) 3-Br
(1d) 4-CH3
(1e) 4-Cl
(1f) 6-CH3
(1g) 6-Cl
(1h) 6-Br
(1i) 7-CH3
(1j) 7-Cl
(1k) 7-Br
(1l) 8-CH3
(1m) 8-Cl
(1n)
9
10
11
12
13
14
15
(1o)
3o
51
aReaction condition: 1 (1.0mmol), 2a (3.0mmol), NH4I (1.2 equiv), NMP (4mL), air, 160°C, 10h.
bStructures were confirmed by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy.
cIsolated yield based on 1.
improved (Table 1, entries 11–14). The optimum reaction at other positions were unreactive (Table 2, entries 2, 4, 6,
time was therefore about 10h (Table 1, entry 11). When the 9, and 12). Besides, 2-methylquinoxaline and 1-methyl-
reaction was carried out under N2, the yield of 3a decreased isoquinoline also exhibited excellent reactivity with ben-
dramatically (Table 1, entry 15), which indicated that the zylamine (2a) under the standard conditions and gave the
mixture required the presence of O2 or air. Subsequently, olefination products 3n in 60% and 3o in 51% yields
the reaction was carried out under an O2 atmosphere and (Table 2, entries 14 and 15).
the yield of target product 3a was found to be almost equal
Subsequently, we set out to examine the substrate scope
to the yield in air (Table 1, entries 11 and 16). So the opti- of various methanamines 2 in reactions with 2-methylqui-
mal reaction conditions were established as follows: using noline (1a). The target products 3 were obtained in good
NH4I as the additive, NMP as the solvent, 160°C, 10h.
yields ranging from 30% to 90% under the optimized con-
With optimized conditions in hand, we set out to ditions. The results are shown in Table 3. The nature of dif-
explore the substrate scope of various quinolines having ferent R groups of benzylamines 2 affected the reaction
sp3 carbons for oxidative cross-dehydrogenative coupling yields slightly. Halogen-substituted benzylamines and
reactions. The target products 3 were obtained in moder- methyl-substituted benzylamines reacted with 1a to afford
ate to good yields ranging from 51% to 93% by reacting the corresponding olefination products in 72%–90% yields
quinolines 1 with benzylamine (2a) in NMP under air at (Table 2, entries 1–8). It is worth noting that naphthalen-α-
160°C for 10h. The results are shown in Table 2. The methanamine (2i) provided the desired product 3x in excel-
nature of the substituents on substrates 1 affected the reac- lent yield 88% (Table 2, entry 9). Besides, a heterocyclic
tion yields to some degree. Both halogen-substituted and methanamine such as 2-thiophene-methanamine (2j) and
methyl-substituted 2-methylquinoline smoothly afforded an aliphatic amine such as cyclohexyl methanamine (2k)
the corresponding products in 54%–93% yields (Table 2, also underwent deamination and were transformed effec-
entries 2–12). Among them, when substituents were tively into the corresponding products 3y and 3z in yields
attached to C-3, C-4, C-6, C-7, or C-8, the yields of the of 73% and 30%, respectively (Table 2, entries 10 and 11).
1
halogen-substituted products were slightly higher than According to the H nuclear magnetic resonance (NMR)
those of the methyl-substituted products. Notably, dime- spectra of olefination products 3 and earlier studies,14–16 we
thyl-substituted quinolines only offered the products of were able to conform the (E)-configurations of the olefina-
olefination at the 2-methyl position, the methyls attached tion products 3.

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Journal of Chemical Research
Table 3. Substrate scope of various primary amines.a
Entry
R
Productb
Yield (%)c
1
2
3
4
5
6
7
8
9
(2a) 2-CH3
(2b) 2-Cl
(2c) 3-CH3
(2d) 3-F
(2e) 3-Cl
(2f) 4-CH3
(2g) 4-F
3p
3q
3r
3s
89
72
76
83
87
90
86
80
88
3t
3u
3v
3w
3x
(2h) 4-Cl
(2i)
10
11
(2j)
3y
3z
73
30
(2k)
aReaction condition: 1a (1.0mmol), 2 (3.0mmol), NH4I (1.2 equiv), NMP (4mL), air, 160°C, 10h.
bStructures were confirmed by 1H and 13C nuclear magnetic resonance (NMR) spectroscopy.
cIsolated yield based on 1a.
To further explore the mechanism of oxidative olefina- without any metal catalyst. The approach provides rela-
tion for the construction of E-2-styrylquinolines, several tively mild reaction conditions, moderate to good yields,
control experiments were carried out. First, when adding and encompasses a broad substrate scope. A plausible
the radical scavenger TEMPO (1.0 equiv) to the standard mechanism has been proposed for the oxidative olefina-
reaction, 3a could be afforded in 84% yield (Scheme 2(a)), tion through deamination.
which suggested that the reaction may not proceed through
a radical intermediate. Second, when 2a alone was sub-
jected to the standard reaction conditions, 30% yield of
Experimental
phenylmethanimine, 10% yield of N-benzylbenzamide, Infrared spectra were determined on a Nicolet Avatar-370
and a trace amount of benzaldehyde were observed spectrometer in KBr (ν in cm–1). Melting points were
(Scheme 2(b)). Finally, when 1a reacted with phenylmeth- measured on a Büchi B-540 capillary melting point appa-
animine under the standard conditions, an 86% yield of 3a ratus and are uncorrected. Mass spectra (ESI-MS) were
was obtained (Scheme 2(c)), suggesting that phenylmetha- recorded on a Thermo Finnigan LCQ-Advantage spec-
nimine might be an intermediate in this reaction.
trometer. High-resolution mass spectra (ESI-HRMS)
Based on these observations and related references,13,15 were obtained using an Agilent 6210 TOF instrument. 1H
a plausible mechanism is proposed in Scheme 3. Initially, NMR and 13C NMR spectra were recorded on a Varian
NH4I is oxidized to a highly active “I+” species in air. Mercury Plus-400 spectrometer (400 and 100 MHz), δ in
Second, the benzylamine is transformed into a phenyl- parts per million, J in Hertz, using TMS as the internal
methanimine by elimination under the influence of “I+.” standard. Signal multiplicities are assigned as singlet (s),
Finally, phenylmethanimine is attacked by the 2-meth- doublet (d), multiplet (m). All analytical reagents were
ylquinoline and is transformed into the corresponding ole- commercially available and were used directly without
fination product via elimination of a molecule of NH3.
further purification.
Conclusion
Synthesis of E-2-styrylquinolines (3a
selected as an example); general procedure
In summary, we have developed an efficient approach for
the synthesis of a variety of E-2-styrylquinolines through A mixture of 2-methylquinoline (1a) (0.14g, 1mmol), ben-
sp3 C-H cross-dehydrogenative coupling of benzylamines zylamine (0.32g, 3.0mmol), and NH4I (0.17g, 1.2mmol)
with 2-methylquinolines promoted by NH4I under air in NMP (4mL) was stirred at 160°C for 10h until the total

Li et al.
5
Scheme 2. Control experiments.
Scheme 3. A plausible mechanism.
consumption of 1a. After cooling, the reaction mixture was 3-Bromo-2-[(1E)-2-phenylethenyl]quinoline (3c). Pale yellow
washed with brine (20mL) and extracted with CH2Cl2 solid; 80%, 0.25g; m.p. 103–105°C (Lit.21 103–105°C).21
(2×20mL). The combined organic extract was dried over 1H NMR (400MHz, CDCl3): δ=8.37 (s, 1H), 8.08–8.03
Na2SO4 and concentrated under vacuum. The residue was (m, 2H), 7.80 (d, J=15.6Hz, 1H), 7.73–7.67 (m, 4H), 7.50
purified by column chromatography (petroleum ether/ (t, J=7.3Hz, 1H), 7.45–7.40 (m, 2H), 7.37–7.32 (m, 1H).
EtOAc=6:1) to afford the target product 3a (pale yellow 13C NMR (100MHz, CDCl3): δ=152.9, 147.0, 139.1,
solid, 85%, 0.20g).
136.9, 136.6, 130.1, 129.2, 128.9, 128.6, 128.4, 127.7,
126.8, 126.5, 124.8, 118.3. MS (ESI): m/z (%)=310.0
([M]+, 51), 312.0([M]+, 49). HRMS (ESI): m/z [M]+ calcd
for C17H1379BrN: 310.0231, found: 310.0239; C17H1381BrN:
312.0211, found: 312.0218.
2-[(1E)-2-phenylethenyl]quinoline (3a). Pale yellow solid;
85%, 0.20 g; m.p. 91–92 °C (Lit.21 91–93 °C).21 1H NMR
(400 MHz, CDCl3): δ = 8.14–8.06 (m, 2H), 7.76 (d,
J = 8.2 Hz, 1H), 7.74–7.64 (m, 5H), 7.55–7.46 (m, 1H),
7.43–7.38 (m, 3H), 7.34–7.30 (m, 1H). 13C NMR
(100 MHz, CDCl3): δ = 156.4, 148.2, 136.6, 136.3, 134.5,
129.7, 129.3, 129.0, 128.9, 128.6, 127.6, 127.5, 127.2,
126.3, 118.9. MS (ESI): m/z (%) = 232.1 ([M]+, 100).
HRMS (ESI): m/z [M]+ calcd for C17H14N: 232.1126,
found: 232.1133.
4-Methyl-2-[(1E)-2-phenylethenyl]quinoline15 (3d). Pale yel-
low solid; 61%, 0.15g; m.p. 122–124°C (Lit.15 122–
123°C). 1H NMR (400MHz, CDCl3): δ=8.04 (d, J=8.0Hz,
1H), 7.75 (d, J=8.0Hz, 1H), 7.56–7.47 (m, 4H), 7.37–7.32
(m, 2H), 7.28–7.24 (m, 3H), 7.22–7.17 (m, 1H), 2.61(s,
3H). 13C NMR (100MHz, CDCl3): δ=156.0, 148.2, 144.3,
136.8, 134.2, 129.8, 129.5, 129.2, 128.8, 128.5, 127.5,
3-Methyl-2-[(1E)-2-phenylethenyl]quinoline (3b). Pale yel- 127.3, 125.9, 123.7, 119.8, 19.2. MS (ESI): m/z (%)=246.1
low solid; 73%, 0.18 g; m.p. 98–100 °C (Lit.21 98– ([M]+, 100). HRMS (ESI): m/z [M]+ calcd for C18H16N:
100 °C).21 1H NMR (400 MHz, CDCl3): δ = 8.09 (d, 246.1283, found: 246.1291.
J = 8.4 Hz, 1H), 8.02 (d, J = 15.6 Hz, 1H), 7.88 (s, 1H),
7.72–7.63 (m, 4H), 7.51 (d, J = 15.6 Hz, 1H), 7.47–7.39 4-Chloro-2-[(1E)-2-phenylethenyl]quinoline (3e). Pale yellow
(m, 3H), 7.35–7.32 (m, 1H), 2.32 (s, 3H). 13C NMR solid; 68%, 0.18g; m.p. 109–111°C (Lit.21 110–111°C).21
(100 MHz, CDCl3): δ = 154.9, 146.9, 137.1, 136.2, 135.6, 1H NMR (400MHz, CDCl3): δ=8.19–8.16 (m, 1H), 8.09
129.4, 129.1, 128.7, 128.6, 128.5, 127.8, 127.5, 126.7, (d, J=8.4Hz, 1H), 7.77–7.72 (m, 2H), 7.69–7.63 (m, 3H),
125.8, 124.3, 19.6. MS (ESI): m/z (%) = 246.1 ([M]+, 7.60–7.56 (m, 1H), 7.43–7.37 (m, 2H), 7.36–7.31 (m, 2H).
100). HRMS (ESI): m/z [M]+ calcd for C18H16N: 13C NMR (100MHz, CDCl3): δ=156.1, 149.2, 142.7,
246.1283, found: 246.1290.
136.2, 135.3, 130.5, 129.5, 128.9, 128.7, 127.9, 127.3,

6
Journal of Chemical Research
127.0, 125.3, 124.0, 119.0. MS (ESI): m/z (%)=266.1 7-Bromo-2-[(1E)-2-phenylethenyl]quinoline (3k). Pale yellow
([M]+, 75), 268.1 ([M]+, 25). HRMS (ESI): m/z [M]+ calcd solid; 87%, 0.27g; m.p. 127–129°C (Lit.14 127–129°C).14
for C17H1335ClN: 266.0736, found: 266.0743; C17H1337ClN: 1H NMR (400MHz, CDCl3): δ=8.22 (d, J=1.6Hz, 1H),
268.0707, found: 268.0716.
8.08 (d, J=8.8Hz, 1H), 7.79–7.74 (m, 5H), 7.65–7.62 (m,
1H), 7.41–7.32 (m, 4H). 13C NMR (100MHz, CDCl3):
6-Methyl-2-[(1E)-2-phenylethenyl]quinoline (3f). Pale yellow δ=156.8, 148.7, 136.4, 136.2, 135.2, 131.7, 129.6, 128.9,
solid; 82%, 0.20g; m.p. 141–143°C (Lit.21 142–144°C).21 128.8, 128.7, 128.4, 127.5, 125.8, 123.8, 119.6. MS (ESI):
1H NMR (400MHz, CDCl3): δ=8.11 (d, J=8.4Hz, 1H), m/z (%)=310.0 ([M]+, 51), 312.0 ([M]+, 49). HRMS
7.97 (d, J=8.8Hz, 1H), 7.67–7.62 (m, 4H), 7.55–7.53 (m, (ESI): m/z [M]+ calcd for C17H1379BrN: 310.0231, found:
2H), 7.43–7.38 (m, 3H), 7.34–7.31 (m, 1H), 2.49 (s, 3H). 310.0238; C17H1381BrN: 312.0211, found: 312.0219.
13C NMR (100MHz, CDCl3): δ=155.3, 146.2, 136.9,
136.2, 135.7, 133.9, 132.0, 129.2, 128.8, 128.6, 128.5, 8-Methyl-2-[(1E)-2-phenylethenyl]quinoline (3l). Pale yellow
127.3, 127.2, 126.4, 118.9, 21.7. MS (ESI): m/z (%)=246.1 solid; 54%, 0.13g; m.p. 72–73°C (Lit.21 72°C).21 1H NMR
([M]+, 100). HRMS (ESI): m/z [M]+ calcd for C18H16N: (400MHz, CDCl3): δ=8.05 (d, J=8.6Hz, 1H), 7.76 (d,
246.1283, found: 246.1290.
J=16.2Hz, 1H), 7.68–7.62 (m, 4H), 7.56 (d, J=6.7Hz,
1H), 7.43–7.31 (m, 5H), 2.76 (s, 3H). 13C NMR (100MHz,
6-Chloro-2-[(1E)-2-phenylethenyl]quinoline (3g). White solid; CDCl3): δ=154.7, 147.2, 137.1, 136.7, 136.3, 133.7, 129.7,
93%, 0.25g; m.p. 147–149°C (Lit.21 148–149°C).21 1H 129.4, 128.7, 128.4, 127.2, 127.1, 125.8, 125.3, 119.2,
NMR (400MHz, CDCl3): δ=8.09 (d, J=8.8Hz, 1H), 8.03 18.4. MS (ESI): m/z (%)=246.1 ([M]+, 100). HRMS (ESI):
(d, J=9.0Hz, 1H), 7.80–7.78 (m, 1H), 7.72–7.61 (m, 5H), m/z [M]+ calcd for C18H16N: 246.1283, found: 246.1289.
7.43–7.31 (m, 4H). 13C NMR (100MHz, CDCl3): δ=156.4,
146.3, 136.6, 135.5, 134.8, 131.7, 130.7, 130.5, 128.9, 8-Chloro-2-[(1E)-2-phenylethenyl]quinoline (3m). Pale yel-
128.6, 128.5, 127.8, 127.3, 126.2, 120.0. MS (ESI): m/z low solid; 59%, 0.16g; m.p. 88–90°C (Lit.16 88–90°C).16
(%)=266.1 ([M]+, 75), 268.1 ([M]+, 25). HRMS (ESI): 1H NMR (400MHz, CDCl3): δ=8.11 (d, J=8.3Hz, 1H),
m/z [M]+ calcd for C17H1335ClN: 266.0736, found: 7.80–7.75 (m, 2H), 7.64–7.68 (m, 4H), 7.47–7.31 (m, 5H).
266.0744; C17H1337ClN: 268.0707, found: 268.0715.
13C NMR (100MHz, CDCl3): δ=156.8, 144.3, 136.6,
136.4, 135.2, 133.1, 129.7, 128.8, 128.7, 128.4, 127.3,
6-Bromo-2-[(1E)-2-phenylethenyl]quinoline (3h). Pale yel- 127.1, 126.4, 125.8, 119.6. MS (ESI): m/z (%)=266.1
low solid; 89%, 0.28g; m.p. 164–166°C (Lit.21 164– ([M]+, 75), 268.1 ([M]+, 25). HRMS (ESI): m/z [M]+ calcd
166°C).21 1H NMR (400MHz, CDCl3): δ=8.11 (d, for C17H1335ClN: 266.0736, found: 266.0745; C17H1337ClN:
J=8.6Hz, 1H), 8.05–7.98 (m, 2H), 7.71–7.68 (m, 1H), 268.0707, found: 268.0715.
7.69–7.61 (m, 4H),7.42–7.31 (m, 4H). 13C NMR
(100MHz, CDCl3): δ=156.6, 147.0, 136.6, 135.5, 135.0, 2-[(1E)-2-phenylethenyl]quinoxaline (3n). Pale yellow solid;
133.0, 130.8, 129.5, 128.9, 128.8, 128.5, 128.4, 127.3, 60%, 0.14g; m.p. 101–103°C (Lit.21 101–103°C).21 1H
120.5, 119.5. MS (ESI): m/z (%)=310.0 ([M]+, 51), 312.0 NMR (400MHz, CDCl3): δ=9.01 (s, 1H), 8.08 (d,
([M]+, 49). HRMS (ESI): m/z [M]+ calcd for C17H1379BrN: J=7.9Hz, 2H), 7.88 (d, J=16.3Hz, 1H), 7.75–7.62 (m,
310.0231, found: 310.0238; C17H1381BrN: 312.0211, 4H), 7.44–7.33 (m, 4H). 13C NMR (100MHz, CDCl3):
found: 312.0219.
δ=150.4, 144.7, 142.4, 141.6, 136.6, 135.9, 130.0, 129.4,
129.3, 129.2, 129.1, 128.9, 127.4, 125.1. MS (ESI): m/z
7-Methyl-2-[(1E)-2-phenylethenyl]quinoline (3i). Pale yel- (%)=233.1 ([M]+, 100). HRMS (ESI): m/z [M]+ calcd for
low solid; 83%, 0.20 g; m.p. 106–108 °C (Lit.21 106– C18H16N: 233.1079, found: 233.1086.
108 °C).21 1H NMR (400 MHz, CDCl3): δ = 8.11 (d,
J = 8.6 Hz, 1H), 7.89–7.86 (m, 1H), 7.66–7.59 (m, 5H), 1-[(1E)-2-phenylethenyl]isoquinoline (3o). Pale yellow solid;
7.41–7.35 (m, 3H), 7.32–7.29 (m, 2H), 2.34 (s, 3H). 13C 51%, 0.12g; m.p. 97–99°C (Lit.21 97–98°C).21 1H NMR
NMR (100 MHz, CDCl3): δ = 156.2, 148.6, 140.0, 136.2, (400MHz, CDCl3): δ=8.58 (d, J=5.6Hz, 1H), 8.36 (d,
136.0, 134.1, 129.1, 128.8, 128.5, 128.4, 128.2, 127.3, J=8.5Hz, 1H), 8.01 (d, J=1.2Hz, 2H), 7.83 (d, J=7.8Hz,
127.1, 125.5, 118.0, 21.9. MS (ESI): m/z (%) = 246.1 1H), 7.72–7.66 (m, 3H), 7.65–7.62 (m, 1H), 7.57 (d,
([M]+, 100). HRMS (ESI): m/z [M]+ calcd for C18H16N: J=5.5Hz, 1H), 7.44–7.41 (m, 2H), 7.35–7.32 (m, 1H). 13C
246.1283, found: 246.1291.
NMR (100MHz, CDCl3): δ=154.6, 142.7, 136.9, 136.7,
135.8, 129.9, 128.7, 128.6, 127.4, 127.3, 127.1, 126.7,
7-Chloro-2-[(1E)-2-phenylethenyl]quinoline (3j). Pale yellow 124.5, 122.8, 119.7. MS (ESI): m/z (%)=232.1 ([M]+,
solid; 90%, 0.24g; m.p. 118–120°C (Lit.21 118–119°C).21 100). HRMS (ESI): m/z [M]+ calcd for C17H14N: 232.1126,
1H NMR (400MHz, CDCl3): δ=7.98–7.97 (m, 2H), 7.82 found: 232.1134.
(d, J=8.2Hz, 1H), 7.80–7.74 (m, 5H), 7.50–7.47 (m, 1H),
7.40–7.37 (m, 3H). 13C NMR (100MHz, CDCl3): δ=156.7, 2-[(1E)-2-(2-Methyl)-phenylethenyl]quinoline (3p). Pale yel-
148.5, 136.3, 136.0, 135.6, 135.0, 128.9, 128.7, 128.6, low solid; 89%, 0.22g; m.p. 69–71°C (Lit.22 69–71°C).21
128.4, 128.1, 127.4, 127.0, 125.6, 119.3. MS (ESI): m/z 1H NMR (400MHz, CDCl3): δ=8.30 (d, J=8.4Hz, 1H),
(%)=266.1 ([M]+, 75), 268.1 ([M]+, 25). HRMS (ESI): 8.06–8.01 (m, 2H), 7.98–7.92 (m, 2H), 7.83–7.77 (m, 2H),
m/z [M]+ calcd for C17H1335ClN: 266.0736, found: 7.60–7.57 (m, 1H), 7.37 (d, J=16.2Hz, 1H), 7.27–7.21 (m,
266.0742; C17H1337ClN: 268.0707, found: 268.0717.
3H), 2.48 (s, 3H). 13C NMR (100MHz, CDCl3): δ=156.4,

Li et al.
7
148.2, 136.9, 136.8, 135.2, 131.9, 131.0, 130.4, 130.3, 136.3, 134.5, 133.6, 129.6, 129.3, 129.0, 127.9, 127.5,
129.1, 129.0, 128.2, 127.6, 126.9, 126.7, 126.2, 120.5, 127.2, 127.1, 126.2, 119.1, 21.2. MS (ESI): m/z (%)=246.1
20.0. MS (ESI): m/z (%)=246.1 ([M]+, 100). HRMS (ESI): ([M]+, 100). HRMS (ESI): m/z [M]+ calcd for C18H16N:
m/z [M]+ calcd for C18H16N: 246.1283, found: 246.1291.
246.1283, found: 246.1292.
2-[(1E)-2-(2-Chloro)-phenylethenyl]quinoline (3q). Pale yel- 2-[(1E)-2-(4-Fluoro)-phenylethenyl]quinoline (3v). Yellow
low solid; 72%, 0.19 g; m.p. 78–80 °C (Lit.22 78–80 °C).21 solid; 86%, 0.21 g; m.p. 120–122 °C (Lit.16 120–122 °C).21
1H NMR (400 MHz, CDCl3): δ = 8.35 (d, J = 8.4 Hz, 1H), 1H NMR (400 MHz, CDCl3): δ = 8.10–8.06 (m, 2H), 7.78
8.11 (d, J = 16.2 Hz, 1H), 8.06–7.98 (m, 2H), 7.95 (d, (d, J = 8.2 Hz, 1H), 7.74–637 (m, 5H), 7.56–7.49 (m, 1H),
J = 8.0 Hz, 1H), 7.83–7.76 (m, 2H), 7.60–7.53 (m, 3H), 7.32 (d, J = 16.2 Hz, 1H), 7.13–77.0 (m, 2H). 13C NMR
7.44–7.37 (m, 2H). 13C NMR (100 MHz, CDCl3): (100 MHz, CDCl3): δ = 163.0 (d, J = 246 Hz), 155.9,
δ = 155.6, 148.2, 137.3, 134.2, 133.4, 132.0, 130.5, 130.4, 148.3, 136.3, 133.4, 132.8 (d, J = 3 Hz), 129.8, 129.2,
130.3, 129.4, 129.2, 128.3, 128.1, 127.8, 127.7, 126.9, 128.9, 128.6 (d, J = 3 Hz), 127.6, 127.3, 126.4, 119.6,
121.0. MS (ESI): m/z (%) = 266.1 ([M]+, 75), 268.1 115.9 (d, J = 22 Hz). MS (ESI): m/z (%) = 250.1 ([M]+,
([M]+, 25). HRMS (ESI): m/z [M]+ calcd for C17H1335ClN: 100). HRMS (ESI): m/z [M]+ calcd for C17H13FN:
266.0736, found: 266.0744; C17H1337ClN: 268.0707, 250.1032, found: 250.1040.
found: 268.0715.
2-[(1E)-2-(4-Chloro)-phenylethenyl]quinoline
(3w). Yellow
2-[(1E)-2-(3-Methyl)-phenylethenyl]quinoline (3r). Pale yellow solid; 80%, 0.21g; m.p. 141–143°C (Lit.16 141–142°C).16 1H
solid; 76%, 0.19g; m.p. 68–69°C (Lit.22 68–69°C).22 1H NMR (400MHz, CDCl3): δ=8.09 (d, J=8.4Hz, 2H), 7.77 (d,
NMR (400MHz, CDCl3): δ=8.33 (d, J=8.4Hz, 1H), 8.10 J=8.0Hz, 1H), 7.72–7.68 (m, 1H), 7.65–87.5 (m, 2H), 7.55–
(d, J=16.2Hz, 1H), 8.04–7.95 (m, 3H), 7.83 (d, J=8.4Hz, 67.4 (m, 3H), 7.36–17.3 (m, 3H). 13C NMR (100MHz,
1H), 7.81–7.78 (m, 1H), 7.40–7.33 (m, 3H), 7.24–7.16 (m, CDCl3): δ=155.7, 148.3, 136.3, 135.1, 134.2, 132.8, 129.8,
2H), 2.34 (s, 3H). 13C NMR (100MHz, CDCl3): δ=156.4, 129.5, 129.1, 128.9, 128.4, 127.5, 127.4, 126.2, 119.2. MS
148.2, 138.3, 136.9, 135.6, 132.1, 131.2, 130.5, 130.3, 129.2, (ESI): m/z (%)=266.1 ([M]+, 75), 268.1 ([M]+, 25). HRMS
129.0, 128.3, 127.5, 126.7, 126.5, 126.2, 120.7, 21.1. MS (ESI): m/z [M]+ calcd for C17H1335ClN: 266.0736, found:
(ESI): m/z (%)=246.1 ([M]+, 100). HRMS (ESI): m/z [M]+ 266.0742; C17H1337ClN: 268.0707, found: 268.0715.
calcd for C18H16N: 246.1283, found: 246.1292.
2-[(1E)-2-(2-(Naphthalen-1-yl))vinyl]quinoline (3x). Yellow
2-[(1E)-2-(3-Fluoro)-phenylethenyl]quinoline (3s). Yellow solid; 88%, 0.25g; m.p. 104–106°C (Lit.22 105–106°C).17
solid; 83%, 0.21 g; m.p. 91–93 °C (Lit.16 91–93 °C).16 1H 1H NMR (400MHz, CDCl3): δ=8.50 (d, J=16.2Hz, 1H),
NMR (400 MHz, CDCl3): δ = 8.12 (d, J = 8.4 Hz, 1H), 8.32 (d, J=8.4Hz, 1H), 8.12 (d, J=8.4Hz, 2H), 7.86–7.71
8.07–48.0 (m, 1H), 7.72–7.67 (m, 2H), 7.58–7.53 (m, (m, 6H), 7.56–7.45 (m, 5H). 13C NMR (100MHz, CDCl3):
2H), 7.52–7.46 (m, 1H), 7.41–317 (m, 4H), 7.01 (t, δ=156.2, 148.3, 136.2, 134.1, 133.7, 131.6, 131.5, 131.3,
J = 8.0 Hz, 1H). 13C NMR (100 MHz, CDCl3): δ = 163.1 129.6, 129.3, 128.8, 128.6, 127.5, 127.4, 126.3, 126.2,
(d, J = 243 Hz), 155.2, 148.1, 138.8 (d, J = 8 Hz), 136.3, 125.8, 125.7, 124.1, 123.8, 119.5. MS (ESI): m/z
132.9 (d, J = 3 Hz), 130.2, 130.0, 129.6, 129.1, 127.4, (%)=282.1 ([M]+, 100). HRMS (ESI): m/z [M]+ calcd for
127.3, 126.1, 123.1 (d, J = 3 Hz), 119.3, 115.2 (d, C21H16N: 282.1283, found: 282.1292.
J = 21 Hz), 113.3 (d, J = 22 Hz). MS (ESI): m/z (%) = 250.1
([M]+, 100). HRMS (ESI): m/z [M]+ calcd for C17H13FN: 2-[(1E)-2-(2-(Thiophen-2-yl))vinyl]quinoline
250.1032, found: 250.1039.
(3y). Yellow
solid; 73%, 0.17g; m.p. 89–91°C (Lit.17 89–91°C).17 1H
NMR (400MHz, CDCl3): δ=8.07–8.00 (m, 2H), 7.84 (d,
2-[(1E)-2-(3-Chloro)-phenylethenyl]quinoline
(3t). Yellow J=16.2Hz, 1H), 7.77–7.72 (m, 2H), 7.56 (d, J=8.4Hz,
solid; 87%, 0.23g; m.p. 90–92°C (Lit.21 90–91°C).21 1H 1H), 7.50–7.47 (m, 1H), 7.30–7.19 (m, 3H), 7.05–7.02 (m,
NMR (400MHz, CDCl3): δ=8.16 (d, J=8.5Hz, 1H), 8.08 1H). 13C NMR (100MHz, CDCl3): δ=155.6, 155.5, 148.2,
(d, J=8.4Hz, 1H), 7.79–37.7 (m, 2H), 7.64–7.61 (m, 3H), 142.1, 136.2, 129.8, 129.1, 128.2, 128.0, 127.7, 127.4,
7.53–7.49 (m, 2H), 7.38 (d, J=16.2Hz, 1H), 7.34–7.29 (m, 127.2, 126.0, 125.9, 119.2. MS (ESI): m/z (%)=238.1
2H). 13C NMR (100MHz, CDCl3): δ=155.6, 148.2, 138.4, ([M]+, 100). HRMS (ESI): m/z [M]+ calcd for C15H12NS:
136.5, 134.6, 132.8, 130.2, 130.1, 129.8, 129.3, 128.4, 238.0690, found: 238.0697.
127.5, 127.3, 127.0, 126.4, 125.4, 119.6. MS (ESI): m/z
(%)=266.1 ([M]+, 75), 268.1 ([M]+, 25). HRMS (ESI): 2-[(1E)-2-(2-Cyclohexylvinyl)]quinoline (3z). Pale yellow oil;
m/z [M]+ calcd for C17H1335ClN: 266.0736, found: 30%, 0.07g.17 1H NMR (400MHz, CDCl3): δ=8.07–8.02
266.0742; C17H1337ClN: 268.0707, found: 268.0715.
(m, 2H), 7.76–7.72 (m, 1H), 7.68–7.63 (m, 1H), 7.54 (d,
J=8.4Hz, 1H), 7.47–7.43 (m, 1H), 6.80–6.76 (m, 1H), 6.66
2-[(1E)-2-(4-Methyl)-phenylethenyl]quinoline
(3u). Yellow (d, J=16.2Hz, 1H), 2.30–2.15 (m, 1H), 1.77–1.64 (m, 4H),
solid; 90%, 0.22g; m.p. 110–112°C (Lit.16 110–112°C).16 1.33–1.19 (m, 6H). 13C NMR (100MHz, CDCl3): δ=156.6,
1H NMR (400MHz, CDCl3): δ=8.08 (m, 2H), 7.77–7.66 148.2, 143.5, 136.2, 129.4, 129.1, 128.5, 127.4, 127.2,
(m, 4H), 7.55 (d, J=8.2Hz, 2H), 7.46 (t, J=7.4Hz, 1H), 125.8, 118.6, 41.0, 32.3, 26.1, 26.0. MS (ESI): m/z
7.38 (d, J=16.2Hz, 1H), 7.22 (d, J=7.9Hz, 2H), 2.35 (s, (%)=238.2 ([M]+, 100). HRMS (ESI): m/z [M]+ calcd for
3H). 13C NMR (100MHz, CDCl3): δ=156.3, 148.2, 138.6, C17H20N: 238.1596, found: 238.1604.

8
Journal of Chemical Research
8. Belley ML, Leger S, Labelle M, et al. Patent 5565473, 1996,
Declaration of conflicting interests
USA.
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
9. Susanta H, Vikas T, Ashutosh V, et al. Org Lett 2020; 22:
5496–5501.
10. Zhang CY, Li ZH, Fang YC, et al. Tetrahedron 2020; 76:
Funding
130968.
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: We
are grateful to the Traditional Chinese Medicine Research Projects
of Health and Family Planning Commission of Jiangxi Province
(No. 2019A228 and 2020B0388) for financial support.
11. Chandan C, Siddiki H and Ken-Ichi S. Tetrahedron Lett
2013; 54: 6490–6493.
12. Matteo S, Nieves C, Maria Laura B, et al. Synlett 2011; 17:
2577–2579.
13. Sharma R, Abdullaha M and Bharate SB. J Org Chem 2017;
82: 9786–9793.
14. Mao D, Zhu XY, Hong G, et al. Synlett 2016; 27: 2481–
ORCID iD
2484.
Xue Li
https://orcid.org/0000-0002-9499-2033
15. Gong L, Xing LJ, Xu T, et al. Org Biomol Chem 2014; 12:
6557–6560.
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