Dioxane-involving reaction for the synthesis of 3-aryl-1-(2-(vinyloxy)ethoxy)isoquinolines catalyzed by AgOTf

Article abstract of DOI:10.1039/c8ob01572d

Dioxane was found to be involved in the reaction of 2-(arylethynyl)benzaldehydes and 3-aminopyrazine-2-carbohydrazide, and underwent a ring-opening reaction catalyzed by AgOTf. This domino type procedure provided an efficient method for the synthesis of 3-aryl-1-(2-(vinyloxy)ethoxy)isoquinolines in good yields via the loss of a molecule of 3-aminopyrazine-2-carboxamide.

Full text of DOI:10.1039/c8ob01572d

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DOI: 10.1039/C8OB01572D
Journal Name
ARTICLE
Dioxane-Involving Reaction for the Synthesis of 3-Aryl-1-(2-
(vinyloxy)ethoxy)isoquinolines Catalyzed by AgOTf
Received 00th January 20xx,
Accepted 00th January 20xx
Wan-Chen Pan, Jian-Quan Liu*, Xiang-Shan Wang*
DOI: 10.1039/x0xx00000x
www.rsc.org/
Dioxane was found to involve in the reaction of 2-(arylethynyl)benzaldehydes and 3-aminopyrazine-2-carbohydrazide, and
underwent a ring-opening reaction catalyzed by AgOTf. This domino type procedure provided an efficient method for the
synthesis of 3-aryl-1-(2-(vinyloxy)ethoxy)isoquinolines in good yields via losing a molecule of 3-aminopyrazine-2-
carboxamide.
Except for the classical isoquinoline synthetic methods, such as
Bischler-Napieralski,5 Pictet-Spengler6 and Pomeranz-Fritsch7
method, the reactions of 2-(arylethynyl)benzaldehydes and various
kinds of nitrogen sources, e.g. NH4OAc,8 NH4HCO3,9 amidine,10
urea,11 hydrazine,12 NH3,13 amine14 and hydroxylamine15 are also
the very expedite procedures to construct 2-substituted
isoquinolines catalyzed by transition metals in recent years. In our
very recent study, the 3-aminopyrazine-2-carbohydrazide (1) was
Introduction
It is well known that isoquinoline derivatives have the remarkable
antibechic activity.1 A representative drug based on isoquinoline
moiety is Codeine2 which is an opiate for treating not only pain but
also cough diseases. Slightly modifying its structure, the analogue
has the same pharmaceutical effect. For example, Pholcodine3 is
also an opioid containing the similar heterocyclic skeleton, and it is
a drug to help suppress unproductive coughs. Therefore, lots of
novel methods have been well-established to construct or
embellish isoquinolines in order to obtain structurally diversified
used as
a nitrogen source to react with 2-(arylethynyl)
benzaldehydes (2), leading to structurally diversified 2-
arylisoquinoline derivatives in high yields catalyzed by iodine under
transition-metal-free conditions.16 As we all know, Ag(I) is a very
efficient catalyst to promote this type of transition.17
analogues in recent years.4
rev ous wor s
P
i
k
H
As a contrast, the same reaction was performed in dioxane by
using AgOTf as the catalyst in our lab. Interestingly, the dioxane was
found to involve in this reaction, affording the unexpected product
3-aryl-1-(2-(vinyloxy)- ethoxy)isoquinolines. As our continuous
study on the construction of heterocycles catalyzed by Lewis acid,18
C
O
r
A
M
ro en sources
Nit
+
g
1
( )
N
r
A
ur recen wor
t
k
O
O
N
we herein report
a novel AgOTf-catalyzed dioxane-involving
H
C
O
r
A
I2
100 o
NHNH2
reaction to synthesize isoquinoline derivatives.
+
2
( )
N
C
N
s
NH2
DM
SO
r
A
u
p t 86 yi ld
%
o
e
w r
Results and discussion
o
Thi
k
O
r
A
H
As shown in Table 1, we began our study on the reaction
condition screening between 1 and 2a as the model substrates. In
the presence of various kinds of Lewis aicds including iodine, CuI,
Cu(OAc)2 and ZnCl2, the reaction in dioxane for 12 h at 100 oC, they
were all ineffective to this conversion (entries 1-4). Even if there
was the stronger acid, e.g. TsOH, also indicated nonreactivity (entry
5). Surprisely, trifluoromethane- sulfonates are indicated an
effective response to this conversion (entries 6-11). Especially for
AgOTf, it promoted the reaction to afford 3a at the highest yield
(83%). When increasing the amount of AgOTf to 10 mol%, there was
little influence on the product yield (entries 13). However, the yield
of 3a decreased distinctly when reduce the amount of catalyst to 1
mol% (entry 12). There was no doubt that the optimized reaction
condition is by using 5 mol% AgOTf in refluxing dioxane.
C
O
N
N
NHNH2
A
Tf
gO
+
3
( )
N
O
NH2
O
O
r
A
O
2
1
3
Scheme 1. Approachs to 2-arylisoquinolines moiety
School of Chemistry and Materials Science, Jiangsu Key Laboratory of Green
Synthesis for Functional Materials, Jiangsu Normal University, Xuzhou Jiangsu
221116, P. R. China Email: liujq316@jsnu.edu.cn; xswang1974@yahoo.com
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [Copies of 1H and 13C NMR
spectra for compounds 3a-3u]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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Table 1. Optimization of the model reactiona
However, other dioxane analogues, such as 1,4-oxathiane,
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morpholine, N-acetyl morpholine20 all did not take part in this
O
DOI: 10.1039/C8OB01572D
Ph
CHO
N
reaction, and only afforded 2-(4-methoxyphenyl)isoquinoline (4) in
83~86% yields (Scheme 3).
NHNH2
acid
Lewis
+
N
O
N
NH2
Table 2. The structurally diversified isoquinoline products 3
Ph
O
3a
O
1
2a
O
O
Ar
CHO
N
N
Entry
1
Catalyst
I2
Amount (mol%)
Yields (%)
NHNH2
R
R
AgOTf
+
N
5
5
5
0
0
0
NH2
O
O
2
CuI
Ar
O
O
1
2
3
3
4
Cu(OAc)2
ZnCl2
5
0
F
5
TsOH
5
0
Cl
6
7
8
9
10
11
12
13
Cu(OTf)2
Sc(OTf)3
Zn(OTf)2
Yb(OTf)3
AgOTf
Bi(OTf)3
AgOTf
AgOTf
5
5
5
5
5
5
1
10
49
52
22
36
83
23
61
83
N
N
N
O
O
O
O
O
O
O
3a
3d
83%
,
3b
79%
,
3c
,
84%
N
N
N
F
Cl
O
O
O
O
O
78%
,
3e
80%
,
3f
82%
,
a
Reaction conditions: 1 (77 mg, 0.5 mmol), 2a (103 mg, 0.5 mmol), dioxane (5.0 mL),
100 °C, 12 h.
O
N
O
N
N
O
Under the optimized reaction conditions, we performed the
similar reactions by varying 2-(arylethynyl)benzaldehydes (Table 2).
Generally, the reactants 219 with both electron-donating (e.g., H,
Me, MeO or OCH2O) and -withdrawing groups (e.g., Cl or Fr) on
benzaldehyde moiety all reacted with 1 smoothly, affording the
corresponding products 3-aryl-1-(2-(vinyloxy) ethoxy)isoquinolines
in good yields (3a-3i, Table 2, 78-84%). Meanwhile, the substituents
on another benzene ring (eg. 3-chloro, 4-chloro, 4-fluoro, 4-
methoxy, 4-ethoxy, 4-methyl, 4-ethyl, 4-propyl, or 4-pentyl) were
well-toleranced, giving the expected products (Table 2, 3j-3r).
Delightly, 1-(phenylethynyl)-2-naphthaldehydes were also chosen
as the reactants to react with 1, and they gave 2-aryl-4-(2-
(vinyloxy)ethoxy)benzo[f]isoquinoline derivatives (Table 2, 3s-3u) in
72-77% yields.
H3CO
O
F
O
O
O
O
3g 82%
,
3h
80%
,
3i
78%
,
Cl
Cl
F
N
O
N
N
O
O
O
O
O
3j
83%
,
3k
85%
,
3l
86%
,
N
N
N
O
O
O
O
O
O
3n
84%
,
3m
79%
,
3o
85%
,
O
O
It worth be noted that 3-(arylethynyl)thiophene-2-carbaldehyde
(2v-2w) with a heteroaryl moiety also could be react with 1 under
the same reaction conditions, leading to thieno[2,3-c]pyridines 3v-
3w in 79% and 82% yields, respectively (Scheme 2).
N
O
N
N
O
O
O
O
O
3p
81%
,
3q
, 83%
O
3r
85%
,
Ar
CHO
S
N
AgOTf
NHNH2
O
N
+
S
N
NH2
O
O
O
Ar
O
N
N
N
1
=
Ar Ph
3v,
79%,
82%,
O
O
3t, 75%
O
O
O
O
=
3w,
Ar 4-MeOC6H4
3s 77%
,
3u
72%
,
aReaction conditions: 1 (77 mg, 0.5 mmol), 2 (0.5 mmol), AgOTf (13 mg, 0.05 mmol),
dioxane (10.0 mL), reflux.
Scheme 2. Aproach to thieno[2,3-c]pyridines
According to the literature12, a plausible reaction mechanism is
proposed in Scheme 4 by using 3a as a model. The key role of AgOTf
is to activate the acetylenic bond, giving rise to the imine addition
to the activated triple bond to afford the intermediate ylide 7.
Subsequently, the oxygen atom in dioxane acts as a nucleophilic
center to attack the imine positive ion, forming the key
intermediate 8. The nitrogen anion in 8 undergoes a protonation
from dioxane moiety to form a carbon-carbon double bond, and the
cleavage of a carbon-oxygen bond takes place to give intermediate
9. Finally, the N-N bond breaks to afford final product 3a via losing a
molecule of 3-amino-pyrazine-2-carboxamide (10).
O
CHO
Ar
N
N
AgOTf
O
NHNH2
+
N
NH2
Ar
2w
X
1
4
=
Ar 4-MeOC6H4
=
X
NH, NAc
S,
Scheme 3. Other attempts for dioxane analogues
2 | J. Name., 2012, 00, 1-3
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Ph
was consumed which was monitored by TLC. TheVidewioAxraticnleeOwnlianes
recovered by distillation under vacuum. TheDrOesI:id10u.e10w39a/sCp8uOrBif0i1e5d72bDy
column chromatography on silica gel using ethyl acetate and
petroleum ether (1:4) as an eluant to give 3a. Changing the ratio to
1:1, the 3-amino-pyrazine-2-carboxamide (10) was obtained in 65%
yield.
O
Ph
O
N
N
NH2
N
N
N
-
H
2O
N
N
H
+
H
O
NH2
NH2
H
5
1
2a
3-Phenyl-1-(2-(vinyloxy)ethoxy)isoquinoline (3a): Yield: 83% (121
mg). Pale yellow solid. M.p. 130∼131 °C; 1H NMR (CDCl3, 400 MHz):
δH 3.88~3.92 (m, 2H, CH2), 4.01~4.04 (m, 1H, CH), 4.11~4.17 (m, 1H,
CH), 4.36 (dd, J = 12.0 Hz, J’ = 2.8 Hz, 1H, CH), 4.50 (dd, J = 12.0 Hz,
J’ = 10.0 Hz, 1H, CH), 5.41 (dd, J = 10.0 Hz, J’ = 2.4 Hz, 1H, CH),
7.38~7.42 (m, 1H, ArH), 7.48~7.51 (m, 2H, ArH), 7.57~7.61 (m, 1H,
ArH), 7.65~7.69 (m, 1H, ArH), 7.87 (d, J = 8.0 Hz, 1H, ArH), 8.04 (s,
1H, ArH), 8.19~8.17 (m, 2H, ArH), 8.39 (d, J = 8.4 Hz, 1H, ArH). 13C
NMR (CDCl3, 100 MHz): δC 66.6, 67.6, 69.8, 76.1, 116.8, 125.5,
126.1, 126.8, 127.1, 127.8, 128.6, 128.7, 130.1, 137.6, 139.2, 149.2,
155.9. IR (KBr): ν 2969, 2914, 2865, 1565, 1497, 1452, 1326, 1275,
1255, 1125, 1102, 1074, 986, 931, 898, 885, 874, 766, 748, 689, 654,
518 cm-1. HRMS (ESI, m/z): Calcd for C19H17NO2Na [M + Na]+
314.1151, found 314.1161.
AgOTf
Ph
Ph
N
O
O
N
N
N
N
N
N
AgOTf
N
H
NH2
NH2
O
O
7
6
Ph
N
Ph
NH2
O
NH2
N
O
N
N
N
N
N
H
H
O
O
N
O
O
H
8
9
NH2
O
Ph
3-Amino-pyrazine-2-carboxamide (10): Yield: 65% (45 mg). Pale
yellow solid. M.p. 240∼241 °C (Lit.20 239 °C); 1H NMR (DMSO-d6,
400 MHz): δH 7.61 (brs, 2H, NH2), 7.80 (d, J = 2.4 Hz, 1H, ArH), 8.09
(brs, 2H, NH2), 8.18 (d, J = 2.4 Hz, 1H, ArH). 13C NMR (DMSO-d6, 100
MHz): δC 125.8, 130.9, 146.7, 155.4, 168.6.
+
N
NH2
N
N
O
O
3a
10
Scheme 4. The possible reaction mechanism
6-Chloro-3-phenyl-1-(2-(vinyloxy)ethoxy)isoquinoline (3b): Yield:
1
79% (128 mg). Pale yellow solid. M.p. 187∼188 °C; H NMR (CDCl3,
400 MHz): δH 3.88~3.92 (m, 2H, CH2), 4.01~4.04 (m, 1H, CH),
The 3-amino-pyrazine-2-carboxamide (10) could be obtained in 4.11~4.17 (m, 1H, CH), 4.33 (dd, J = 12.0 Hz, J’ = 2.8 Hz, 1H, CH),
4.47 (dd, J = 12.0 Hz, J’ = 9.6 Hz, 1H, CH), 5.40 (dd, J = 9.6 Hz, J’ = 2.8
Hz, 1H, CH), 7.44~7.47 (m, 2H, ArH), 7.59~7.70 (m, 2H, ArH), 7.87 (d,
J = 8.0 Hz, 1H, ArH), 8.01 (s, 1H, ArH), 8.08~8.12 (m, 2H, ArH), 8.39
(d, J = 8.4 Hz, 1H, ArH). 13C NMR (CDCl3, 100 MHz): δC 66.6, 67.6,
69.7, 76.1, 116.3, 124.7, 126.6, 126.8, 128.79, 128.83, 129.3, 131.2,
132.7, 135.9, 138.7, 149.5, 155.2. IR (KBr): ν 3064, 2963, 2919, 2855,
1590, 1576, 1566, 1499, 1481, 1448, 1386, 1296, 1256, 1198, 1140,
1122, 1105, 1084, 935, 901, 834, 808, 756, 733, 691 cm-1. HRMS
(ESI, m/z): Calcd for C19H17NO2 [M + H]+ 326.0942, found 326.0959.
65% yield in the subsequent column chromatography separation,
increasing the ratio of ethyl acetate and petroleum ether to 1:1.
The isolation of 10 is a potent evidence for above-mentioned
reaction mechanism.
Conclusions
In conclusion, using dioxane as a solvent catalyzed by AgOTf, it
was involved in the reaction of 3-aminopyrazine-2-carbohydrazide
and 2-(arylethynyl)benzaldehydes and underwent a ring-opening
6-Fluoro-3-phenyl-1-(2-(vinyloxy)ethoxy)isoquinoline (3c): Yield:
1
84% (130 mg). Pale yellow solid. M.p. 176∼177 °C; H NMR (CDCl3,
reaction
to
give
3-aryl-1-(2-(vinyloxy)ethoxy)isoquinoline
400 MHz): δH 3.84~3.93 (m, 2H, CH2), 4.00~4.04 (m, 1H, CH),
4.09~4.13 (m, 1H, CH), 4.36 (dd, J = 12.0 Hz, J’ = 2.8 Hz, 1H, CH),
4.46 (dd, J = 12.0 Hz, J’ = 9.6 Hz, 1H, CH), 5.35 (dd, J = 9.6 Hz, J’ = 2.8
Hz, 1H, CH), 7.31~7.36 (m, 1H, ArH), 7.40~7.51 (m, 4H, ArH), 7.98 (s,
1H, ArH), 8.13~8.15 (m, 2H, ArH), 8.44 (dd, J = 9.2 Hz, J’ = 5.6 Hz, 1H,
ArH). 13C NMR (CDCl3, 100 MHz): δC 66.6, 67.6, 69.7, 76.3, 110.8 (d,
JC-F = 20.5 Hz), 116.2 (d, JC-F = 5.2 Hz), 117.4 (d, JC-F = 25.1 Hz), 123.3,
126.9, 128.8, 128.865, 128.866 (d, JC-F =9.5 Hz), 138.8, 139.3 (d, JC-F
=10.4 Hz), 150.1, 156.0, 163.0 (d, JC-F = 251.0 Hz). IR (KBr): ν 2967,
2921, 2851, 1628, 1572, 1501, 1458, 1418, 1296, 1208, 1120, 1099,
964, 927, 895, 874, 847, 764, 690, 674, 631 cm-1. HRMS (ESI, m/z):
Calcd for C19H16FNO2Na [M + Na]+ 332.1057, found 332.1046.
derivatives in good yields.
Experimental
Melting points were determined in open capillaries and are
uncorrected. IR spectra were recorded on a Tensor 27 spectrometer
in KBr pellet. NMR spectra were obtained from a solution in DMSO-
d6 or CDCl3 with Me4Si as internal standard using a Bruker-400
spectrometer. HRMS analyses were carried out using a Bruker-
micro-TOF-Q-MS analyzer. All the starting materials were
purchased from Beijing InnoChem Science & Technology Co., Ltd
except for 2-(arylethynyl)benzaldehydes which were prepared from
the reaction of substituted 2-bromobenzoaldehydes and arynes
according to the literature.19
6-Methyl-3-phenyl-1-(2-(vinyloxy)ethoxy)isoquinoline (3d): Yield:
1
78% (119 mg). Pale yellow solid. M.p. 162∼163 °C; H NMR (CDCl3,
400 MHz): δH 2.54 (s, 3H, CH3), 3.88~3.90 (m, 2H, CH2), 4.02 (d, J =
10.4 Hz, 1H, CH), 4.10~4.13 (m, 1H, CH), 4.34 (dd, J = 12.0 Hz, J’ =
2.8 Hz, 1H, CH), 4.48 (dd, J = 12.0 Hz, J’ = 10.0 Hz, 1H, CH), 5.38 (dd,
J = 10.0 Hz, J’ = 2.8 Hz, 1H, CH), 7.40~7.43 (m, 2H, ArH), 7.47~7.51
(m, 2H, ArH), 7.63 (s, 1H, ArH), 7.95 (s, 1H, ArH), 8.14~8.15 (m, 2H,
ArH), 8.26~8.28 (m, 1H, ArH). 13C NMR (CDCl3, 100 MHz):δC 20.9,
65.6, 66.6, 68.8, 75.1, 115.3, 123.5, 124.2, 125.6, 125.8, 127.4,
127.6, 128.4, 136.9, 138.3, 139.3, 148.2, 154.6. IR (KBr): ν 2955,
General procedure for the syntheses of 3 (Using 3a as a model)
3-Aminopyrazine-2-carbohydrazide (77 mg, 0.5 mmol), 2-
(phenylethynyl)benz- aldehydes (103 mg, 0.5 mmol), AgOTf (13 mg,
0.05 mmol), and dioxane (5.0 mL) was added into a dry 25 mL flask.
The reaction mixture was stirred at reflux for 8-12 h until all the 2
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2923, 2853, 1571, 1560, 1541, 1517, 1501, 1457, 1375, 1324, 1289, 7-Phenyl-5-(2-(vinyloxy)ethoxy)-[1,3]dioxolo[4,5-g]isoquinoline
View Article Online
1256, 1121, 1101, 1077, 1050, 951, 934, 902, 874, 838, 807, 744, (3i): Yield: 78% (131 mg). Pale yellow solid. M.p. 179∼180 °C; 1H
DOI: 10.1039/C8OB01572D
682 cm-1. HRMS (ESI, m/z): Calcd for C20H20NO2 [M + H]+ 306.1489, NMR (CDCl3, 400 MHz): δH 3.86~3.90 (m, 2H, CH2), 3.99~4.01 (m,
found 306.1487.
1H, CH), 4.08~4.14 (m, 1H, CH), 4.34 (dd, J = 12.0 Hz, J’ = 2.4 Hz, 1H,
CH), 4.47 (dd, J = 12.0 Hz, J’ = 9.6 Hz, 1H, CH), 5.22 (dd, J = 9.6 Hz, J’
= 2.8 Hz, 1H, CH), 6.09~6.10 (m, 2H, OCH2), 7.11 (s, 1H, ArH),
7.36~7.40 (m, 1H, ArH), 7.45~7.49 (m, 2H, ArH), 7.64 (s, 1H, ArH),
7.87 (s, 1H, ArH), 8.09~8.11 (m, 2H, ArH). 13C NMR (CDCl3, 100
MHz): δC 66.6, 67.6, 69.7, 76.5, 101.7, 101.8, 103.4, 116.5, 123.4,
126.6, 128.3, 128.7, 136.2, 139.3, 148.4, 148.5, 150.5, 153.9. IR
(KBr): ν 2973, 2911, 2852, 1594, 1577, 1490, 1462, 1430, 1352,
1255, 1232, 1188, 1115, 1078, 1040, 980, 951, 925, 902, 876, 776,
691 cm-1. HRMS (ESI, m/z): Calcd for C20H17NO2Na [M + Na]+
358.1050, found 358.1062.
7-Chloro-3-phenyl-1-(2-(vinyloxy)ethoxy)isoquinoline (3e): Yield:
80% (130 mg). Pale yellow solid. M.p. 160∼161 °C; H NMR (CDCl3,
1
400 MHz): δH 3.84~3.93 (m, 2H, CH2), 4.02~4.05 (m, 1H, CH),
4.12~4.18 (m, 1H, CH), 4.36 (dd, J = 12.0 Hz, J’ = 2.8 Hz, 1H, CH),
4.46 (dd, J = 12.0 Hz, J’ = 9.6 Hz, 1H, CH), 5.32 (dd, J = 9.6 Hz, J’ = 2.8
Hz, 1H, CH), 7.40~7.44 (m, 1H, ArH), 7.48~7.52 (m, 2H, ArH),
7.60~7.62 (m, 1H, ArH), 7.81 (d, J = 8.8 Hz, 1H, ArH), 8.01 (s, 1H,
ArH), 8.13~8.15 (m, 2H, ArH), 8.38 (s, 1H, ArH). 13C NMR (CDCl3, 100
MHz): δC 66.6, 67.6, 69.7, 76.1, 116.3, 124.7, 126.6, 126.8, 128.79,
128.83, 129.3, 131.2, 132.7, 135.9, 138.7, 149.5, 155.2. IR (KBr): ν
2960, 2945, 2921, 2855, 1569, 1541, 1507, 1489, 1453, 1404, 1374, 3-(3-Chlorophenyl)-1-(2-(vinyloxy)ethoxy)isoquinoline (3j): Yield:
1
1322, 1294, 1254, 1224, 1193, 1118, 1104, 1078, 1049, 934, 896, 83% (135 mg). Pale yellow solid. M.p. 140∼141 °C; H NMR (CDCl3,
872, 795, 762 cm-1. HRMS (ESI, m/z): Calcd for C19H17ClNO2 [M + H]+ 400 MHz): δH 3.86~3.93 (m, 2H, CH2), 4.02~4.05 (m, 1H, CH),
326.0942, found 326.0963.
4.11~4.18 (m, 1H, CH), 4.44 (dd, J = 12.0 Hz, J’ = 2.8 Hz, 1H, CH),
4.48 (dd, J = 12.0 Hz, J’ = 9.6 Hz, 1H, CH), 5.41 (dd, J = 9.6 Hz, J’ = 2.8
Hz, 1H, CH), 7.36~7.44 (m, 2H, ArH), 7.61~7.72 (m, 2H, ArH), 7.89 (d,
J = 8.0 Hz, 1H, ArH), 8.02~8.04 (m, 2H, ArH), 8.16 (t, J = 2.0 Hz, 1H,
ArH), 8.40 (d, J = 8.4 Hz, 1H, ArH). 13C NMR (CDCl3, 100 MHz): δC
66.6, 67.6, 69.8, 76.0, 117.1, 124.8, 125.5, 126.3, 127.0, 127.6,
127.8, 128.5, 129.9, 130.3, 134.8, 137.5, 141.0, 147.7, 156.2. IR
(KBr): ν 2970, 2916, 1868, 1623, 1567, 1496, 1446, 1374, 1326,
1277, 1256, 1126, 1094, 1074, 1050, 937, 903, 875, 782, 751, 701,
685, 675 cm-1. HRMS (ESI, m/z): Calcd for C19H17ClNO2 [M + H]+
326.0942, found 326.0956.
7-Fluoro-3-phenyl-1-(2-(vinyloxy)ethoxy)isoquinoline (3f): Yield:
82% (127 mg). Pale yellow solid. M.p. 160∼161 °C; H NMR (CDCl3,
1
400 MHz): δH 3.87~3.93 (m, 2H, CH2), 4.02~4.05 (m, 1H, CH),
4.11~4.17 (m, 1H, CH), 4.37 (dd, J = 12.0 Hz, J’ = 2.8 Hz, 1H, CH),
4.46 (dd, J = 12.0 Hz, J’ = 9.6 Hz, 1H, CH), 5.31 (dd, J = 9.6 Hz, J’ = 2.8
Hz, 1H, CH), 7.41~7.52 (m, 4H, ArH), 7.88 (dd, J = 8.8 Hz, J’ = 5.6 Hz,
1H, ArH), 8.02~8.05 (m, 2H, ArH), 8.13~8.15 (m, 2H, ArH). 13C NMR
(CDCl3, 100 MHz): δC 66.6, 67.6, 69.6, 76.4, 109.3 (d, JC-F = 21.9 Hz),
116.36, 116.38, 120.8 (d, JC-F = 25.5 Hz), 126.7, 128.7, 128.8, 130.2
(d, JC-F = 8.6 Hz), 134.7, 138.9, 148.8 (d, JC-F = 2.6 Hz), 155.4 (d, JC-F
=
5.9 Hz), 160.7 (d, JC-F = 247.0 Hz). IR (KBr): ν 2951, 2908, 2856, 1593, 3-(3-Fluorophenyl)-1-(2-(vinyloxy)ethoxy)isoquinoline (3k): Yield:
1
1571, 1499, 1454, 1408, 1369, 1356, 1324, 1293, 1258, 1224, 1120, 85% (131 mg). Pale yellow solid. M.p. 167∼168 °C; H NMR (CDCl3,
1118, 1089, 1035, 918, 876, 805, 782, 697 cm-1. HRMS (ESI, m/z): 400 MHz): δH 3.88~3.92 (m, 2H, CH2), 4.01~4.03 (m, 1H, CH),
Calcd for C19H16FNO2Na [M + Na]+ 332.1057, found 332.1048.
4.11~4.17 (m, 1H, CH), 4.34 (dd, J = 12.0 Hz, J’ = 2.4 Hz, 1H, CH),
4.48 (dd, J = 12.0 Hz, J’ = 10.0 Hz, 1H, CH), 5.39 (dd, J = 10.0 Hz, J’ =
2.8 Hz, 1H, CH), 7.06~7.11 (m, 1H, ArH), 7.41~7.46 (m, 1H, ArH),
7.59~7.63 (m, 1H, ArH), 7.66~7.69 (m, 1H, ArH), 7.85~7.92 (m, 3H,
ArH), 8.01 (s, 1H, ArH), 8.38 (d, J = 8.4 Hz, 1H, ArH). 13C NMR (CDCl3,
100 MHz): δC 66.6, 67.6, 69.7, 75.9, 113.7 (d, JC-F = 22.7 Hz), 115.3 (d,
JC-F = 21.3 Hz), 117.0, 122.2 (d, JC-F = 2.7 Hz), 125.5, 126.3, 127.5,
127.8, 130.1 (d, JC-F = 8.1 Hz), 130.3, 137.4, 141.5 (d, JC-F = 7.7 Hz),
147.7 (d, JC-F = 2.3 Hz), 156.1, 163.4 (d, JC-F = 243.2 Hz). IR (KBr): ν
2951, 2921, 2858, 1578, 1491, 1456, 1258, 1246, 1173, 1164, 1120,
1100, 1081, 1050, 951, 914, 873, 818, 788, 701, 636 cm-1. HRMS
(ESI, m/z): Calcd for C19H16FNO2Na [M + Na]+ 332.1057, found
332.1050.
7-Methoxy-3-phenyl-1-(2-(vinyloxy)ethoxy)isoquinoline (3g): Yield:
82% (132 mg). Pale yellow solid. M.p. 118∼119 °C; H NMR (CDCl3,
1
400 MHz): δH 3.88~3.92 (m, 2H, CH2), 3.98 (s, 3H, OCH3), 4.02~4.05
(m, 1H, CH), 4.11~4.17 (m, 1H, CH), 4.35 (dd, J = 12.0 Hz, J’ = 2.8 Hz,
1H, CH), 4.51 (dd, J = 12.0 Hz, J’ = 9.6 Hz, 1H, CH), 5.35 (dd, J = 9.6
Hz, J’ = 2.8 Hz, 1H, CH), 7.33~7.40 (m, 2H, ArH), 7.46~7.50 (m, 2H,
ArH), 7.65 (d, J = 2.4 Hz, 1H, ArH), 7.78 (d, J = 9.2 Hz, 1H, ArH), 7.98
(s, 1H, ArH), 8.12~8.14 (m, 2H, ArH). 13C NMR (CDCl3, 100 MHz): δC
55.4, 66.6, 67.5, 69.7, 76.3, 103.4, 116.6, 122.9, 126.5, 127.2, 128.2,
128.7, 129.3, 133.2, 139.3, 147.5, 154.1, 158.2. IR (KBr): ν 2958,
2923, 2851, 1571, 1498, 1458, 1412, 1363, 1260, 1239, 1215, 1186,
1123, 1099, 1079, 1036, 969, 941, 903, 875, 820, 772, 699 cm-1.
HRMS (ESI, m/z): Calcd for C20H20NO3 [M + H]+ 322.1438, found 3-(4-Chlorophenyl)-1-(2-(vinyloxy)ethoxy)isoquinoline (3l): Yield:
322.1443.
1
86% (140 mg). Pale yellow solid. M.p. 155∼156 °C; H NMR (CDCl3,
400 MHz): δH 3.85~3.92 (m, 2H, CH2), 4.01~4.04 (m, 1H, CH),
4.11~4.17 (m, 1H, CH), 4.33 (dd, J = 12.0 Hz, J’ = 2.8 Hz, 1H, CH),
4.47 (dd, J = 12.0 Hz, J’ = 9.6 Hz, 1H, CH), 5.40 (dd, J = 9.6 Hz, J’ = 2.8
Hz, 1H, CH), 7.44~7.47 (m, 2H, ArH), 7.59~7.70 (m, 2H, ArH), 7.87 (d,
J = 8.0 Hz, 1H, ArH), 8.01 (s, 1H, ArH), 8.08~8.12 (m, 2H, ArH), 8.39
(d, J = 8.4 Hz, 1H, ArH). 13C NMR (CDCl3, 100 MHz): δC 66.6, 67.6,
69.8, 76.0, 116.7, 125.5, 126.2, 127.4, 127.8, 128.1, 128.9, 130.3,
134.6, 137.5, 137.7, 148.0, 156.1. IR (KBr): ν 2958，2921, 2850,
1595, 1571, 1497, 1458, 1442, 1374, 1324, 1272, 1253, 1120, 1107,
1091, 1009, 984，933，902, 871, 834, 748, 718, 683 cm-1. HRMS
(ESI, m/z): Calcd for C19H17ClNO2 [M + H]+ 326.0942, found
326.0960.
8-Fluoro-3-phenyl-1-(2-(vinyloxy)ethoxy)isoquinoline (3h): Yield:
80% (124 mg). Pale yellow solid. M.p. 156∼157 °C; H NMR (CDCl3,
1
400 MHz): δH 3.85~3.89 (m, 2H, CH2), 3.98~4.02 (m, 1H, CH),
4.10~4.16 (m, 1H, CH), 4.37 (dd, J = 11.6 Hz, J’ = 2.4 Hz, 1H, CH),
4.47~4.53 (m, 1H, CH), 5.55 (dd, J = 9.6 Hz, J’ = 2.4 Hz, 1H, CH),
7.22~7.28 (m, 1H, ArH), 7.40~7.44 (m, 1H, ArH), 7.48~7.52 (m, 2H,
ArH), 7.57~7.62 (m, 1H, ArH), 7.66~7.68 (m, 1H, ArH), 8.03 (d, J =
2.0 Hz, 1H, ArH), 8.14~8.17 (m, 2H, ArH). 13C NMR (CDCl3, 100 MHz):
δC 66.6, 68.1, 70.0, 76.9, 112.9 (d, JC-F = 23.7 Hz), 116.0 (d, JC-F = 3.3
Hz), 116.6 (d, JC-F = 14.2 Hz), 124.0 (d, JC-F = 4.3 Hz), 126.9, 128.8,
128.9, 130.4 (d, JC-F = 9.3 Hz), 138.5, 139.9 (d, JC-F = 3.7 Hz), 149.7 (d,
JC-F = 1.8 Hz), 154.0 (d, JC-F = 6.7 Hz), 159.2 (d, JC-F = 255.6 Hz). IR
(KBr): ν 2952, 2923, 2852, 1570, 1559, 1541, 1507, 1457, 1375, 3-(p-Tolyl)-1-(2-(vinyloxy)ethoxy)isoquinoline (3m): Yield: 79%
1324, 1258, 1218, 1126, 918, 895, 876, 864, 830, 782, 696 cm-1. (120 mg). Pale yellow solid. M.p. 143∼144 °C; H NMR (CDCl3, 400
1
HRMS (ESI, m/z): Calcd for C19H16NO2Na [M + Na]+ 332.1057, found MHz): δH 2.42 (s, 3H, CH3), 3.88~3.92 (m, 2H, CH2), 4.01~4.04 (m,
332.1051.
1H, CH), 4.11~4.18 (m, 1H, CH), 4.35 (dd, J = 12.0 Hz, J’ = 2.8 Hz, 1H,
CH), 4.50 (dd, J = 12.0 Hz, J’ = 10.0 Hz, 1H, CH), 5.40 (dd, J = 10.0 Hz,
4 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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ARTICLE
J’ = 2.8 Hz, 1H, CH), 7.29~7.31 (m, 2H, ArH), 7.56~7.60 (m, 1H, ArH), 76.1, 114.1, 115.6, 125.4, 125.7, 126.8, 127.6, 128.1, 130.0, 131.9,
7.64~7.68 (m, 1H, ArH), 7.86 (d, J = 8.0 Hz, 1H, ArH), 8.01 (s, 1H, 137.7, 149.0, 155.8, 160.2. IR (KBr): ν 2956, D2O92I:61,02.18053V99ie,/Cw185AOr7ti0Bcl0,e11O55n71l2in6De,
ArH), 8.05~8.07 (m, 2H, ArH), 8.38 (d, J = 8.0 Hz, 1H, ArH). 13C NMR 1446, 1402, 1325, 1306, 1289, 1248, 1201, 1179, 1120, 1100, 1035,
(CDCl3, 100 MHz): δC 21.3, 66.6, 67.6, 69.8, 76.1, 116.2, 125.4, 125.9, 931, 902, 893, 875, 826, 743, 728, 692 cm-1. HRMS (ESI, m/z): Calcd
126.7, 126.9, 127.7, 129.4, 130.0, 136.4, 137.6, 138.5, 149.2, 155.8. for C20H20NO3 [M + H]+ 322.1438, found 322.1448.
IR (KBr): ν 3053, 2945, 2853, 1569, 1558, 1516, 1456, 1443, 1369,
1327, 1273, 1253, 1184, 1141, 1123, 1100, 1075, 987, 931, 901, 874,
829, 815, 749 cm-1. HRMS (ESI, m/z): Calcd for C20H20NO2 [M + H]+
306.1489, found 306.1490.
3-(4-Ethoxyphenyl)-1-(2-(vinyloxy)ethoxy)isoquinoline (3r): Yield:
1
85% (142 mg). Pale yellow solid. M.p. 155∼156 °C; H NMR (CDCl3,
400 MHz): δH 1.46 (t, J = 7.2 Hz, 3H, CH3), 3.88~3.91 (m, 2H, CH2),
4.01~4.03 (m, 1H, CH), 4.08~4.17 (m, 3H, OCH2+CH), 4.35 (dd, J =
3-(4-Ethylphenyl)-1-(2-(vinyloxy)ethoxy)isoquinoline (3n): Yield: 12.0 Hz, J’ = 2.8 Hz, 1H, CH), 4.50 (dd, J = 12.0 Hz, J’ = 10.0 Hz, 1H,
1
84% (134 mg). Pale yellow solid. M.p. 103∼104 °C; H NMR (CDCl3, CH), 5.39 (dd, J = 10.0 Hz, J’ = 2.8 Hz, 1H, CH), 7.00~7.02 (m, 2H,
400 MHz): δH 1.28 (t, J = 7.6 Hz, 3H, CH3), 2.72 (q, J = 7.6 Hz, 2H, ArH), 7.54~7.58 (m, 1H, ArH), 7.62~7.66 (m, 1H, ArH), 7.83 (d, J =
CH2), 3.88~3.92 (m, 2H, CH2), 4.01~4.04 (m, 1H, CH), 4.11~4.17 (m, 8.0 Hz, 1H, ArH), 7.95 (s, 1H, ArH), 8.09~8.11 (m, 2H, ArH), 8.36 (d, J
1H, CH), 4.36 (dd, J = 12.0 Hz, J’ = 2.4 Hz, 1H, CH), 4.50 (dd, J = 12.0 = 8.4 Hz, 1H, ArH). 13C NMR (CDCl3, 100 MHz): δC 14.9, 63.5, 66.6,
Hz, J’ = 9.6 Hz, 1H, CH), 5.40 (dd, J = 9.6 Hz, J’ = 2.4 Hz, 1H, CH), 67.6, 69.8, 76.1, 114.6, 115.5, 125.4, 125.7, 126.7, 127.6, 128.1,
7.32~7.34 (m, 2H, ArH), 7.55~7.60 (m, 1H, ArH), 7.64~7.68 (m, 1H, 130.0, 131.7, 137.7, 149.0, 155.7, 159.5. IR (KBr): ν 2968, 2956,
ArH), 7.86 (d, J = 8.4 Hz, 1H, ArH), 8.01 (s, 1H, ArH), 8.07~8.09 (m, 2923, 2861, 1592, 1571, 1515, 1478, 1446, 1429, 1391, 1305, 1285,
2H, ArH), 8.38 (d, J = 8.8 Hz, 1H, ArH). 13C NMR (CDCl3, 100 MHz): δC 1253, 1199, 1181, 1119, 1101, 1077, 1050, 984, 933, 901, 873, 824,
15.6, 28.7, 66.6, 67.6, 69.8, 76.1, 116.3, 125.5, 126.0, 126.8, 126.9, 806, 741, 726, 698 cm-1. HRMS (ESI, m/z): Calcd for C21H21NO3Na [M
127.7, 128.3, 130.0, 136.7, 137.6, 144.9, 149.3, 155.8. IR (KBr): ν + Na]+ 358.1414, found 358.1437.
2949, 2920, 2854, 1591, 1559, 1541, 1516, 1490, 1457, 1445, 1374,
1325, 1287, 1254, 1185, 1119, 1101, 983, 932, 901, 833, 740, 690
cm-1. HRMS (ESI, m/z): Calcd for C21H21NO2Na [M + Na]+ 342.1465,
found 342.1493.
2-Phenyl-4-(2-(vinyloxy)ethoxy)benzo[f]isoquinoline (3s): Yield:
1
77% (131 mg). Pale yellow solid. M.p. 192∼193 °C; H NMR (CDCl3,
400 MHz): δH 3.91~3.92 (m, 2H, CH2), 4.03~4.06 (m, 1H, CH),
4.12~4.20 (m, 1H, CH), 4.38 (dd, J = 12.0 Hz, J’ = 2.4 Hz, 1H, CH),
3-(4-Propylphenyl)-1-(2-(vinyloxy)ethoxy)isoquinoline (3o): Yield: 4.55 (dd, J = 12.0 Hz, J’ = 9.6 Hz, 1H, CH), 5.44 (dd, J = 9.6 Hz, J’ = 2.4
1
85% (142 mg). Pale yellow solid. M.p. 133∼134 °C; H NMR (CDCl3, Hz, 1H, CH), 7.42~7.46 (m, 1H, ArH), 7.52~7.56 (m, 2H, ArH),
400 MHz): δH 0.98 (t, J = 7.2 Hz, 3H, CH3), 1.65~1.74 (m, 2H, CH2), 7.69~7.72 (m, 2H, ArH), 7.82~7.84 (m, 1H, ArH), 7.91~7.94 (m, 1H,
2.66 (t, J = 7.6 Hz, 2H, CH2), 3.88~3.91 (m, 2H, CH2), 4.01~4.04 (m, ArH), 8.21~8.24 (m, 3H, ArH), 8.75~8.77 (m, 1H, ArH), 8.85 (s, 1H,
1H, CH), 4.11~4.18 (m, 1H, CH), 4.36 (dd, J = 12.0 Hz, J’ = 2.8 Hz, 1H, ArH). 13C NMR (CDCl3, 100 MHz): δC 65.6, 67.7, 69.9, 76.0, 112.3,
CH), 4.50 (dd, J = 12.0 Hz, J’ =9.6 Hz, 1H, CH), 5.40 (dd, J = 9.6 Hz, J’ 122.3, 124.4, 127.07, 127.12, 128.2, 128.6, 128.7, 128.8, 129.1,
= 2.8 Hz, 1H, CH), 7.29~7.32 (m, 2H, ArH), 7.56~7.60 (m, 1H, ArH), 133.2, 136.5, 139.6, 151.1, 155.2. IR (KBr): ν 2973, 2907, 2857, 1578,
7.64~7.68 (m, 1H, ArH), 7.60 (d, J = 8.0 Hz, 1H, ArH), 8.01 (s, 1H, 1519, 1505, 1442, 1429, 1293, 1254, 1238, 1172, 1121, 1092, 1077,
ArH), 8.06~8.08 (m, 2H, ArH), 8.38 (d, J = 8.4 Hz, 1H, ArH). 13C NMR 1035, 945, 900, 876, 822, 763, 746 cm-1. HRMS (ESI, m/z): Calcd for
(CDCl3, 100 MHz): δC 13.9, 24.6, 37.8, 66.6, 67.6, 69.8, 76.1, 116.3, C23H19NO2Na [M + Na]+ 364.1308, found 364.1335.
125.4, 125.9, 126.7, 126.9, 127.7, 128.9, 130.0, 136.7, 137.6, 143.3,
149.3, 155.8. IR (KBr): ν 2958, 2922, 2854, 1591, 1570, 1516, 1447,
1374, 1325, 1289, 1256, 1185, 1121, 1101, 1077, 985, 934, 902, 875,
838, 809, 745, 732, 683 cm-1. HRMS (ESI, m/z): Calcd for
C22H23NO2Na [M + Na]+ 356.1621, found 356.1647.
2-(4-Methoxyphenyl)-4-(2-(vinyloxy)ethoxy)benzo[f]isoquinoline
(3t): Yield: 75% (139 mg). Pale yellow solid. M.p. 184∼185 °C; 1H
NMR (CDCl3, 400 MHz): δH 3.93~3.95 (m, 5H, OCH3+CH2), 4.06~4.08
(m, 1H, CH), 4.16~4.23 (m, 1H, CH), 4.40 (dd, J = 12.0 Hz, J’ = 2.8 Hz,
1H, CH), 4.58 (dd, J = 12.0 Hz, J’ = 9.6 Hz, 1H, CH), 5.46 (dd, J = 9.6
3-(4-Pentylphenyl)-1-(2-(vinyloxy)ethoxy)isoquinoline (3p): Yield: Hz, J’ = 2.4 Hz, 1H, CH), 7.08~7.10 (m, 2H, ArH), 7.72~7.75 (m, 2H,
1
81% (146 mg). Pale yellow solid. M.p. 143∼144 °C; H NMR (CDCl3, ArH), 7.84(d, J = 9.2 Hz, 1H, ArH), 7.94~7.97 (m, 1H, ArH), 8.21~8.25
400 MHz): δH 0.9 (t, J = 6.4 Hz, 3H, CH3), 1.33~1.37 (m, 4H, 2CH2), (m, 3H, ArH), 8.78~8.81 (m, 2H, ArH). 13C NMR (CDCl3, 100 MHz): δC
1.63~1.70 (m, 2H, CH2), 2.67(t, J = 7.6 Hz, 2H, CH2), 3.89~3.91 (m, 55.4, 66.6, 67.7, 69.9, 76.0, 111.3, 114.2, 122.4, 123.2, 124.0, 127.0,
2H, CH2), 4.01~4.04 (m, 1H, CH), 4.11~4.17 (m, 1H, CH), 4.36 (dd, J = 127.8, 128.3, 128.6, 128.7, 129.1, 132.3, 133.2, 136.6, 150.9, 155.1,
12.0 Hz, J’ = 2.4 Hz, 1H, CH), 4.48~4.53 (m, 1H, CH), 5.40 (dd, J = 9.6 160.3. IR (KBr): ν 2958, 1919, 1858, 1578, 1505, 1456, 1442, 1430,
Hz, J’ = 2.4 Hz, 1H, CH), 7.30~7.32 (m, 2H, ArH), 7.56~7.60 (m, 1H, 1293, 1255, 1239, 1172, 1720, 1093, 1078, 1035, 947, 914, 875, 763
ArH), 7.64~7.68 (m, 1H, ArH), 7.86(d, J = 8.4 Hz, 1H, ArH), 8.01 (s, cm-1. HRMS (ESI, m/z): Calcd for C24H21NO3Na [M + Na]+ 394.1414,
1H, ArH), 8.06~8.08 (m, 2H, ArH), 8.38(d, J = 8.4 Hz, 1H, ArH). 13C found 394.1433.
NMR (CDCl3, 100 MHz): δC 14.1, 22.6, 31.2, 31.5, 35.7, 66.6, 67.6,
69.8, 76.1, 116.3, 125.4, 125.9, 126.7, 126.9, 127.7, 128.8, 130.0,
136.7, 137.6, 143.6, 149.3, 155.8. IR (KBr): ν 2950, 2918, 2858, 1591,
1566, 1517, 1468, 1448, 1374, 1327, 1275, 1254, 1126, 1103, 1074,
1021, 988, 933, 899, 875, 848, 811, 747, 697 cm-1. HRMS (ESI, m/z):
Calcd for C24H28NO2 [M + H]+ 362.2115, found 362.2123.
2-(4-Ethylphenyl)-4-(2-(vinyloxy)ethoxy)benzo[f]isoquinoline (3u):
1
Yield: 72% (133 mg). Pale yellow solid. M.p. 140∼141 °C; H NMR
(CDCl3, 400 MHz): δH 1.31 (t, J = 7.6 Hz, 3H, CH3), 2.74 (q, J = 7.6 Hz,
2H, CH2), 3.90~3.92 (m, 2H, CH2), 4.02~4.05 (m, 1H, CH), 4.13~4.20
(m, 1H, CH), 4.38 (dd, J = 12.0 Hz, J’ = 2.0 Hz, 1H, CH), 4.53~4.58 (m,
1H, CH), 5.43 (dd, J = 10.0 Hz, J’ = 2.4 Hz, 1H, CH), 7.35~7.37 (m, 2H,
3-(4-Methoxyphenyl)-1-(2-(vinyloxy)ethoxy)isoquinoline
(3q): ArH), 7.69~7.71 (m, 2H, ArH), 7.81 (d, J = 9.2 Hz, 1H, ArH), 7.91~7.93
1
Yield: 83% (133 mg). Pale yellow solid. M.p. 143∼144 °C; H NMR (m, 1H, ArH), 8.14~8.16 (m, 2H, ArH), 8.21 (d, J = 9.2 Hz, 1H, ArH),
(CDCl3, 400 MHz): δH 3.88 (s, 3H, OCH3), 3.89~3.92 (m, 2H, CH2), 8.75~8.77 (m, 1H, ArH), 8.82 (s, 1H, ArH). 13C NMR (CDCl3, 100
4.01~4.04 (m, 1H, CH), 4.11~4.17 (m, 1H, CH), 4.35 (dd, J = 12.0 Hz, MHz): δC 15.6, 28.7, 66.6, 67.6, 69.9, 76.0, 111.9, 122.4, 123.2,
J’ = 2.8 Hz, 1H, CH), 4.50 (dd, J = 12.0 Hz, J’ = 9.6 Hz, 1H, CH), 5.40 124.2, 127.1, 127.9, 128.3, 128.6, 128.7, 129.1, 133.2, 136.5, 137.1,
(dd, J = 9.6 Hz, J’ = 2.4 Hz, 1H, CH), 7.01~7.04 (m, 2H, ArH), 145.1, 151.2, 155.1. IR (KBr): ν 2969, 2953, 2916, 1588, 1580, 1512,
7.54~7.58 (m, 1H, ArH), 7.63~7.67 (m, 1H, ArH), 7.84(d, J = 8.4 Hz, 1495, 1486, 1441, 1427, 1411, 1293, 1266, 1252, 1225, 1093, 1054,
1H, ArH), 7.96 (s, 1H, ArH), 8.09~8.13 (m, 2H, ArH), 8.36 (d, J = 8.0 987, 902, 820 cm-1. HRMS (ESI, m/z): Calcd for C25H23NO2Na [M +
Hz, 1H, ArH). 13C NMR (CDCl3, 100 MHz): δC 55.4, 66.6, 67.6, 69.8, Na]+ 392.1656, found 392.1648.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
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Organic & Biomolecular Chemistry
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ARTICLE
Journal Name
5-Phenyl-7-(2-(vinyloxy)ethoxy)thieno[2,3-c]pyridine (3v): Yield:
79% (177 mg). Pale yellow solid. M.p. 77∼78 °C; 1H NMR (CDCl3, 400
Physiol. Pharmacol., 1989, 67, 561. (d) B. Kelentei, Acta.
View Article Online
Pharm. Hung., 1969, 39, 247.
DOI: 10.1039/C8OB01572D
MHz): δH 3.81~3.88 (m, 2H, CH2), 3.94 (dd, J = 12.0 Hz, J’ = 10.0 Hz, 2. (a) F. Herrera-Gomez, M. Garcia-Mingo, M. Colas, J. C. Gonzalez-
1H, CH), 4.00~4.01 (m, 2H, CH2), 4.38 (dd, J = 12.0 Hz, J’ = 3.2 Hz,
1H, CH), 5.16 (dd, J = 10.0 Hz, J’ = 2.8 Hz, 1H, CH), 7.38~7.41 (m, 2H,
ArH), 7.46~7.50 (m, 2H, ArH), 7.71 (d, J = 5.2 Hz, 1H, ArH), 8.05~8.08
(m, 3H, ArH). 13C NMR (CDCl3, 100 MHz): δC 65.5, 65.8, 68.8, 77.6,
Luque, F. J. Alvarez, Drug Alcohol Depen., 2018, 187, 35. (b)
M. H. Y. Tang, C. K. Ching, S. Poon, S. S. S. Chan, W. Y. Ng, M.
Lam, C. K. Wong, R. Pao, A. Lau, T. W. L. Mak, Forensic Sci. Int.,
2018, 286, 113.
112.5, 121.8, 125.9, 127.4, 127.7, 130.7, 132.6, 138.4, 146.6, 149.6, 3. (a) E. Florvaag, S. G. O. Johansson, Allergy, 2012, 67, 581. (b) P. H.
151.1. IR (KBr): ν 2960, 2923, 2855, 1579, 1513, 1491, 1453, 1400,
M. Sadleir, R. C. Clarke, D. L. Bunning, P. R. Platt, Brit. J.
Anaesth., 2013, 110, 981.
1302, 1283, 1258, 1247, 1196, 1175, 1135, 1112, 1099, 1082, 1030,
966, 906, 875 cm-1. HRMS (ESI, m/z): Calcd for C17H15NO2Na [M + 4. (a) M. Chrzanowska, A. Grajewska, M. D. Rozwadowska, Chem.
Na]+ 320.0716, found 320.0726.
Rev., 2016, 116, 12369. (b) S. Tang, S. W. Yang, H. W. Sun, Y. L.
Zhou, J. Li, Q. Zhu, Org. Lett., 2018, 20, 1832. (c) W. F. Tian, D.
P. Wang, S. F. Wang, K. H. He, X. P. Cao, Y. Li, Org. Lett., 2018,
20, 1421. (d) F. W. Ding, Y. Q. Jiang, K. F. Lin, L. Shi, Org.
Biomol. Chem., 2018, 16, 1812. (e) Y. Y. Yang, Y. X. Li, C.
Cheng, G. Yang, J. Q. Zhang, Y. Zhang, Y. L. Zhao, L. Zhang, C.
Li, L. Tang, J. Org. Chem., 2018, 83, 3348. (f) C. X. Xie, Z. Dai, Y.
D. Niu, C. Ma, J. Org. Chem., 2018, 83, 2317. (g) J. X. Zhao, B.
R. Lichman, J. M. Ward, H. C. Hailes, Chem. Commun., 2018,
54, 1323.
5-(4-Methoxyphenyl)-7-(2-(vinyloxy)ethoxy)thieno[2,3-c]pyridine
1
(3w): Yield: 82% (134 mg). Pale yellow solid. M.p. 101∼102 °C; H
NMR (CDCl3, 400 MHz): δH 3.83~3.95 (m, 5H, OCH3 + CH2), 3.93 (dd,
J = 12.0 Hz, J’ = 10.0 Hz, 1H, CH), 4.00~4.11 (m, 2H, CH2), 4.37 (dd, J
= 12.0 Hz, J’ = 3.2 Hz, 1H, CH), 5.14 (dd, J = 10.0 Hz, J’ = 3.2 Hz, 1H,
CH), 7.00~7.02 (m, 2H, ArH), 7.36~7.37 (m, 1H, ArH), 7.68 (d, J = 5.6
Hz, 1H, ArH), 7.97 (s, 1H, ArH), 8.00~8.04 (m, 2H, ArH). 13C NMR
(CDCl3, 100 MHz): δC 54.3, 65.5, 65.8, 68.8, 77.6, 111.6, 113.1, 121.7,
127.1, 130.0, 131.0, 132.5, 146.6, 149.4, 150.9, 159.0. IR (KBr): ν
2960, 2923, 1606, 1573, 1513, 1453, 1400, 1259, 1247, 1175, 1112,
1098, 1030, 906, 875, 829 cm-1. HRMS (ESI, m/z): Calcd for
C18H18NO3 [M + H]+ 320.1002, found 320.0988.
5. K. H. Kim, C. H. Cheon, Cheon, Adv. Synth. Catal., 2016, 358,
2883.
6. V. Erdmann, B. R. Lichman, J. X. Zhao, R. C. Simon, Angew. Chem.
Int. Ed., 2017, 56, 12503.
7. M. Leonardi, M. Villacampa, J. C. Menendez, J. Org. Chem., 2017,
82, 2570.
8. M. E. Domaradzki, L. Long, Z. She, X. Liu, G. Zhang, Y. Chen, J. Org.
Chem., 2015, 80, 11360.
General procedure for the synthese of 2-(4-methoxyphenyl)
isoquinoline (4)
9. Y. H. Zhao, M. J. Luo, Y. B. Li, X. Liu, Z. L. Tang, K. Q. Deng, G. Zhao,
Chin. J. Chem., 2016, 34, 857.
10. K. Shekarrao, P. P. Kaishap, S. Gogoi, R. C. Boruah, RSC Adv.,
2014, 4, 14013.
11. J. Ju, R. Hua, Curr. Org. Chem., 2013, 10, 328.
12. Y. H. Zhao, Y. Li, M. Luo, Z. Tang, K. Deng, Synlett, 2016, 27,
2597.
13. M. Alfonsi, M. D. Acqua, D. Facoetti, A. Arcadi, G. Abbiati, Eur. J.
Org. Chem., 2009, 2852.
14. M. Jeganathan, K. Pitchumani, RSC Adv., 2014, 4, 38491.
15. H. Y. Gao, J. L. Zhang, Adv. Synth. Catal., 2009, 351, 85.
16. W. C. Pan, J. Q. Liu, X. S. Wang, Tetrahedron, 2018, 74, 1468.
17. (a) S. Y. Xing, H. Cui, N. Gu, Y. Li, K. Wang, D. Tian, J. J. Liu, Q. Y.
Qin, Org. Biomol. Chem., 2017, 15, 8308. (b) X. Cheng, X. Cao,
J. Xuan, W. J. Xiao, Org. Lett., 2018, 20, 52. (c) D. Basavaiah, P.
Thamizharasi, Eur. J. Org. Chem., 2017, 5135. (d) J. J. Song, C.
B. Fan, G. Liu, G. Y. S. Qiu, Org. Chem. Front., 2014, 1, 1045.
(e) X. B. Wang, X. X. Yu, J. Org. Chem., 2014, 79, 7863. (f) Z. H.
Liu, H. M. Ji, W. Gao, G. Y. Zhu, L. L. Tong, F. C. Lei, B. Tang,
Chem. Commun., 2017, 53, 6259. (g) J. Sheng, C. B. Fan, Y. C.
Ding, X. N. Fan, J. Wu, Chem. Commun., 2014, 50, 4188. (h) Q.
Xiao, J. Sheng, Q. P. Ding, J. Wu, Adv. Synth. Catal., 2013, 355,
2321.
18. (a) B. B. Feng, J. Q. Liu, X. S. Wang, J. Org. Chem., 2017, 82,
1817. (b) J. Q. Liu, X. Y. Shen, Z. H. Liu, X. S. Wang, Org. Biomol.
Chem., 2017, 15, 6314. (c) B. B. Feng, L. Lu, C. Li, X. S. Wang,
Org. Biomol. Chem., 2016, 14, 2774.
19. K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett., 1975,
16, 4467.
3-Aminopyrazine-2-carbohydrazide (77 mg, 0.5 mmol), 2-
(phenylethynyl)benzaldehydes (118 mg, 0.5 mmol), AgOTf (13 mg,
0.05 mmol), and dioxane analogues (5.0 mL) was added into a dry 25
mL flask. The reaction mixture was stirred at 100 °C until all the 2
was consumed which was monitored by TLC. About 50mL water
was added to the mixture (1,4-oxathiane was recovered by
distillation under vacuum first), and then extracted by ethyl acetate.
After desiccation by anhydrous sodium sulfate, the solvent was
recovered by rotary evaporation. The residue was purified by
column chromatography on silica gel using ethyl acetate and
petroleum ether (1:4) as an eluant to give 4.
3-(4-Methoxyphenyl)isoquinoline (4): M.p. 104∼105 °C (Lit.16 105-
106 °C); 1H NMR (CDCl3, 400 MHz): δH 3.88 (s, 3H, OCH3), 7.03~7.05
(m, 2H, ArH), 7.53~7.56 (m, 1H, ArH), 7.65~7.68 (m, 1H, ArH), 7.83
(d, J = 8.4 Hz, 1H, ArH), 7.95~7.98 (m, 2H, ArH), 8.07~8.09 (m, 2H,
ArH), 9.30 (s, 1H, ArH). 13C NMR (CDCl3, 100 MHz): δC 55.4, 114.2,
115.4, 126.7, 126.8, 127.4, 127.6, 128.2, 130.5, 132.3, 136.8, 151.1,
152.3, 160.1.
Acknowledgements
This work was financially supported by NSFC of China (No.
21702078), NSF of Jiangsu Province (No. BK20170231), Natural
Science Foundation of Jiangsu Higher Education Institution
(17KJA150003), the open project of Northeast Normal University
(130028830), the Priority Academic Program Development of
Jiangsu Higher education Institution, and TAPP.
20. R. C. Ellingson, R. L. Henry, F. G. McDonald, J. Am. Chem. Soc.,
1945, 67, 1711.
Notes and references
1. (a) Z. R. Yang, M. Liu, X. L. Peng, X. F. Lei, J. X. Zhang, W. G. Dong,
Biochem. Biophys. Res. Commun., 2012, 421, 627. (b) L.
Alisaraie, J. A. Tuszynski, Chem. Biol. Drug Des., 2011, 78, 535.
(c) J. Church, M. G. Jones, S. N. Davies, D. Lodge, Can. J.
6 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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DOI: 10.1039/C8OB01572D
Table of Contents Entry
Dioxane-Involving Reaction for the Synthesis of 3-Aryl-1-(2-(vinyloxy)ethoxy)
isoquinolines Catalyzed by AgOTf
Wan-Chen Pan, Jian-Quan Liu*, Xiang-Shan Wang*
School of Chemistry and Materials Science, Jiangsu Key Laboratory of Green Synthesis for
Functional Materials, Jiangsu Normal University, Xuzhou Jiangsu 221116, P. R. China
xswang1974@yahoo.com
Dioxane was involved in the reaction of 2-(arylethynyl)benzaldehydes and 3-aminopyrazine-
2-carbohydrazide, and underwent a ring-opening reaction catalyzed by AgOTf to give
3-aryl-1-(2-(vinyloxy)ethoxy)isoquinolines in good yields.