Cu(OAc)2-Catalyzed Aerobic Oxidative Dehydrogenation Coupling: Synthesis of Heptacyclic Quinolizino[3,4,5,6-kla]perimidines

Article abstract of DOI:10.1021/acs.joc.6b02644

A Cu(OAc)₂-catalyzed domino tricyclization between naphthalene-1,8-diamine and 2-(phenylethynyl)benzaldehyde is described, enabling aerobic oxidative dehydrogenation coupling to access heptacyclic quinolizino[3,4,5,6-kla]perimidines. In this reaction, the formation of three new rings and four new bonds was achieved in a functional-group-compatible fashion, allowing a facile method toward fused aza-heterocycles containing both quinolizine and perimidine moieties.

Full text of DOI:10.1021/acs.joc.6b02644

Subscriber access provided by Caltech Library
Note
Cu(OAc)2-Catalyzed Aerobic Oxidative Dehydrogenation Coupling:
Synthesis of Heptacyclic Quinolizino[3,4,5,6-kla]perimidines
Bin-Bin Feng, Jianquan Liu, and Xiang-Shan Wang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02644 • Publication Date (Web): 28 Dec 2016
Downloaded from http://pubs.acs.org on December 28, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 18
The Journal of Organic Chemistry
1
2
3
4
5
Cu(OAc)2-Catalyzed Aerobic Oxidative Dehydrogenation Coupling: Synthesis of
Heptacyclic Quinolizino[3,4,5,6-kla]perimidines
6
7
Bin-Bin Feng, Jian-Quan Liu*, Xiang-Shan Wang*
8
9
School of Chemistry and Chemical Engineering, Jiangsu Key Laboratory of Green
Synthesis for Functional Materials, Jiangsu Normal University, Xuzhou Jiangsu
221116, P. R. China
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
xswang1974@yahoo.com, liujq316@jsnu.edu.cn
Abstract: A Cu(OAc)2-catalyzed domino tricyclization between naphthalene-1,8-diamine and
2-(phenylethynyl)benzaldehyde is described, enabling aerobic oxidative dehydrogenation coupling
to access heptacyclic quinolizino[3,4,5,6-kla]perimidines. In this reaction, the formation of three
new rings and four new bonds was achieved in a functional-group-compatible fashion, allowing a
facile method toward fused aza-heterocycles containing both quinolizine and perimidine moieties.
Keywords: quinolizinoperimidine, hydroamination, oxidative dehydrogenation, Cu(OAc)2
Oxidative dehydrogenation coupling of aromatic C(sp2)-H bonds is a highly
efficient approach for the synthesis of biaryls.1 Learning from the previous reports,
valuable metals have been largely employed, for example, Pd,2 Mo,3 Rh,4 and Ru.5 In
2- 7
the presence of various oxidizing agents, such as Ag+,6 S2O8 or TBHP,8 especially
,
for air or oxygen,9 only a molecule of water loses from the reactants, therefore, it has
good atom economy concerning about green chemistry. In the past few years, it has
been used in organic synthesis to construct structurally diversified biphenyls or
polycyclic
heterocycles.10,11
As
we
all
know,
heptacyclic
quinolizino[3,4,5,6-kla]perimidine is a highly-conjugated heterocycle of which the
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 18
1
2
3
4
5
6
7
8
9
derivatives are widely applied in electronic materials, such as in dye lasers and
electroluminescent materials.12 In 2011, Fujii and co-workers13 reported the two-step
procedure for the generation of heptacyclic quinolizino[3,4,5,6-kla] perimidines
through a copper-catalyzed bicyclization between ortho-(2-bromophenyl)ethynyl
substituted arylaldehydes with 1,8-diaminonaphthalene, and a palladium-catalyzed
C-H arylation in sequence (Scheme 1a). However, backbone bromo-functional group
was required for the C-H arylation process.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 1. Synthesis of heptacyclic quinolizino[3,4,5,6-kla]perimidines
C-H activation
Fujii' work
Br
H
NH2 NH2
CHO
[Cu]
N
N
[Pd]
N
N
+
(a)
Br
- HBr
oxidative coupling dehydrogenation
This work
NH2 NH2
H
H
CHO
Cu(OAc)2
N
N
N
+
H
Cs2CO3
(b)
- H2O
N
O2 (1.0 atm)
1
2
3
Broad substrate scope
Pd-free
High efficiency, high yield
Enlightened by this reaction, we reasoned that under suitable catalytic oxidation
conditions, tricyclization of 2-alkynylbenzaldehydes and 1,8-diaminonaphthalene
could be achieved in one-pot operation through aerobic oxidative coupling and
dehydrogenation, enabling C(sp2)-C(sp2) bond formation to access highly-conjugated
heptacyclic quinolizino[3,4,5,6-kla]perimidines under Pd- and halogen-free conditions.
Based on the above analysis, we selected Cu(OAc)2 as a catalyst to conduct this
reaction considering its low-cost and high catalytic activity.14 As part of our
continuing interest in the design of copper-catalyzed domino reaction for significant
aza-heterocycle synthesis,15 herein, we would like to report this copper-catalyzed
ACS Paragon Plus Environment

Page 3 of 18
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
domino tricyclization for the synthesis of heptacyclic quinolizino[3,4,5,6-kla]
perimidines via a sequential cyclization, alkyne hydroamination, oxidative
dehydrogenation coupling (Scheme 1b).
9
We began our optimization studies with 1,8-diaminonaphthalene (1) and
2-(phenylethynyl)benzaldehyde (2a) as model substrates with verifying the catalysts,
oxidants, bases, solvent and temperature (Table 1). Initially, this reaction was carried
out in the presence of Cu(OAc)2 (1.2 equiv) at 130 °C in DMSO under an argon
atmosphere.14 However, only trace product of 3a was observed by TLC. Different
oxidants, such as PhI(OAc)2, K2S2O8, Ag2O, DDQ, and air were employed and the
expected product 3a was obtained in 8% yield under air conditions whereas other
oxidants completely suppressed the reaction process (entries 2-5). Furthermore,
various bases including K2CO3, Cs2CO3, Na2CO3 and NaHCO3 were evaluated
(entries 7-10). Among the bases tested, the use of Cs2CO3 (100 mol%) resulted in the
best result with a 16% yield (entry 8), whereas isoquinolino[2,1-a]perimidine
intermediate 4a was isolated in a 66% yield. Decreasing the loading of Cu(OAc)2 to
20 mol% also furnished 3a with a 16% yield under air conditions (entry 12). Further
decrease the dosage of Cu(OAc)2 was adverse to the yield of 3a (entry 13). To our
delight, the yield of 3a was improved to 62% dramatically under an oxygen
atmosphere in the presence of 1.0 equiv of Cs2CO3 in DMSO (entry 14). Afterward,
solvent effect was investigated. THF, 1,4-dioxane, and toluene were tested, and
1,4-dioxane was proved to be the best media for this tricyclization, delivering 3a in a
76% yield (entry 14). Compared to Cu(OAc)2, other copper (II) salts (CuCl2 and
Cu(OTf)2) were completely ineffective for this transformation. Moreover, the copper
(I) species, CuI was also reactive affording desired product 3a in a 71% yield (entry
20).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 18
1
2
3
Table 1. Optimization studies for copper-mediated oxidative coupling and dehydrogenation a
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
entry
Cat. (mol%)
oxidant (mol%)
baseb
solvent
Yield (3a) % c
1
Cu(OAc)2(120)
Cu(OAc)2(120)
Cu(OAc)2(120)
Cu(OAc)2(120)
Cu(OAc)2(120)
Cu(OAc)2(120)
Cu(OAc)2(120)
Cu(OAc)2(120)
Cu(OAc)2(120)
Cu(OAc)2(120)
Cu(OAc)2(50)
Cu(OAc)2(20)
Cu(OAc)2(10)
-
-
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
trace
trace
trace
trace
trace
8
2
PhI(OAc)2(100)
-
3
K2S2O8(100)
-
4
Ag2O(100)
DDQ(100)
Air
-
5
-
6
-
7
Air
K2CO3
Cs2CO3
Na2CO3
NaHCO3
Cs2CO3
Cs2CO3
Cs2CO3
12
8
Air
16
9
Air
10
10
11
12
13
Air
10
Air
15
Air
16
Air
12
14
15
16
17
18
19
20
Cu(OAc)2(20)
Cu(OAc)2(20)
Cu(OAc)2(20)
Cu(OAc)2(20)
CuCl2(20)
O2
O2
O2
O2
O2
O2
O2
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
DMSO
Dioxane
THF
62
76
21
Toluene
Dioxane
Dioxane
Dioxane
69
trace
trace
70
Cu(OTf)2(20)
CuI(20)
a Reagents and conditions: 1 (158 mg, 1.0 mmol), 2a (206 mg, 1.0 mmol), solvent (10.0 mL),
reflux. b Base: 1.0 mmol; c Isolated yields; d 130 °C; e refluxing.
With the optimized reaction conditions in hand, the reaction scope of this
tricyclization was investigated carefully. As shown in Table 2, a wide range of
substituted fused quinolizino[3,4,5,6-kla] perimidines 3a-3s was synthesized from the
corresponding 2-alkynylbenzaldehydes. The benzaldehyde moieties with different
functional groups on the benzene ring, including Me, MeO, F, and Cl, were tolerated
ACS Paragon Plus Environment

Page 5 of 18
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
well under the reaction conditions. The electronic effect of substituents (R1) has no
significant impact on the reaction efficiency. Further, the arylalkynyl moiety with
diverse substituent groups (R2) was explored. It was found that both electron-donating,
such as EtO, n-Pr and MeO group, and electron-withdrawing groups (Cl and F atom)
on the arylalkynyl moiety were compatible and furnished the expected heptacyclic
quinolizino[3,4,5,6-kla]perimidines 3j-3t with yields ranging from 67% to 80%.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 2. Synthetic results of 3 via oxidative coupling and dehydrogenation a
R2
R2
CHO
Cu(OAc)2 (20 mol% )
Cs2CO3 (1.0 equiv.)
NH2
NH2
N
+
1,4-dioxane, 100 oC
O2
R1
N
R1
1
3
2
N
N
N
N
N
N
N
Cl
O
N
O
F
3a, 76%
3b, 78%
3c, 72%
3d, 69%
N
N
N
N
N
N
N
F
OMe
N
OMe
Cl
OMe
3e, 78%
3f, 71%
3g, 81%
EtO
3h, 72%
EtO
EtO
N
N
N
N
N
N
N
OMe
N
OMe
Cl
3i, 73%
3j, 77%
3k, 80%
3l, 67%
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 18
1
2
3
EtO
EtO
MeO
4
5
6
7
8
9
N
N
N
N
N
N
N
N
F
O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
O
Cl
3m, 69%
MeO
3n, 73%
Cl
3o, 80%
Cl
3p, 75%
F
N
N
N
N
N
N
N
N
OMe
Cl
Cl
3q, 78%
3s, 80%
3r, 76%
3t, 77%
a
Reagents and conditions: 1 (158 mg, 1.0 mmol), 2 (1.0 mmol), Cu(OAc)2 (36 mg, 0.2 mmol),
Cs2CO3 (325 mg, 1.0 mmol), dioxane (10.0 mL) under an O2 balloon, 100 oC
.
However, 2-(4-nitrophenylethynyl)benzaldehyde with strong electron-with-
drawing group (NO2) failed to give the desired heptacyclic product, instead of leading
to the formation of 13-(4-nitrophenyl)isoquinolino[2,1-a]perimidine 4u with a 88%
yield under the standard reaction conditions. In addition, when
2-(3-fluorophenylethynyl)-5-chlorobenzaldehyde 2t was used as the substrate, the
product 13-chloro-6-fluorodibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine 3t was
obtained in a 77% yield with high regioselectivity.
According to the above experimental results (for details, see the supporting
information) and literature reports14, a possible mechanism for forming products 3
was proposed in scheme 2. The reaction process involves a successive condensation,
nucleophilic addition, intramolecular alkyne hydroamination, oxidative
dehydrogenation coupling sequence. The success of this tricyclization is a key
oxidative dehydrogenation coupling. Intermediate 711a,16 may be formed through
oxidative
exchange
of
Cu(OAc)2
with
intermediate
product
ACS Paragon Plus Environment

Page 7 of 18
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
isoquinolino[2,1-a]perimidines 4. Cu(OAc)2 plausibly performs disproportionation14
to produce CuOAc which helps 7 occur oxidative addition to form 8 containing
copper(III). The copper(III) inserts the Ar-H bond to yield intermediate 9, then 9
performs reductive elimination to deliver the final product 3. Finally, the regeneration
of Cu(OAc)2 catalyst to complete the catalytic cycle is by oxidation of O2.
H2O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
4
Cu(OAc)2
HOAc
O2
+
HOAc
CuOAc
AcOCu
3
N
N
7
Cu(OAc)2
AcO
Cu
(AcO)2Cu
N
CuOAc
N
N
9
N
8
HOAc
Scheme 2. The possible reaction mechanism
In conclusion, we have presented a novel approach for the synthesis of
dibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidines catalyzed by Cu(OAc)2 under O2
conditions. This domino protocol provides a concise access to fused heptacyclic
heterocycles bearing quinolizine and perimidine moieties.
Experimental Section
General procedure for the syntheses of 3.
A
reaction flask with high vacuum valve was charged with
naphthalene-1,8-diamine (158 mg, 1.0 mmol), 2-(arylethynyl)benzaldehyde (1.0
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 18
1
2
3
4
5
6
mmol), Cu(OAc)2 (36 mg, 0.2 mmol), Cs2CO3 (325 mg, 1.0 mmol). After three times
in vacuum and oxygen of replacement, dioxane (10.0 mL) was injected into the
7
8
o
mixture. And then, the reaction mixture was stirred at 100 C under an O2 balloon
9
before reaching completion, which was monitored by TLC. The solvent was
recovered by distillation under reduced pressure, and the residue was purified by
chromatography over silica gel to give 3 using ethyl acetate and petroleum ether
(1:16) as an eluent.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Dibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine (3a). Yield 76% (260 mg).
Pale yellow solid, m.p. 122~124 °C (Lit.13 124~126 °C); 1H NMR (CDCl3, 400 MHz):
δH 7.48~7.52 (m, 1H), 7.62~7.69 (m, 3H), 7.77~7.81 (m, 1H), 7.93 (d, J = 9.2 Hz,
1H), 8.14~8.20 (m, 3H), 8.23~8.26 (m, 2H), 8.35 (d, J = 8.0 Hz, 1H), 8.47 (d, J = 8.0
Hz, 1H), 8.64 (d, J = 7.6 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δC 112.1, 118.2,
121.4, 121.9, 122.3, 122.69, 123.3, 123.4, 124.9, 125.1, 126.4, 127.0, 127.8, 128.2,
128.8, 129.4, 130.1, 130.14, 131.7, 131.8, 133.4, 135.3, 137.2, 140.7, 143.2. IR
(KBr):
ν 3051, 1707, 1616, 1574, 1547, 1507, 1473, 1423, 1400, 1365, 1301, 1243,
1212, 1170, 1122, 1076, 1009, 821, 791, 754, 691, 658 cm-1. HRMS (TOF, ESI, m/z):
Calcd for C25H15N2 [M+H]+ 343.1236, found 343.1235.
12-Chlorodibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine (3b). Yield 78%
1
(294 mg). Pale yellow solid, m.p. 240~242 °C; H NMR (CDCl3, 400 MHz): δH
7.50~7.54 (m, 1H), 7.59~7.61 (m, 1H), 7.67~7.71 (m, 2H), 7.93 (d, J = 8.8 Hz, 1H),
8.12~8.15 (m, 2H), 8.18 (d, J = 7.6 Hz, 1H), 8.21~8.28 (m, 3H), 8.46 (d, J = 8.0 Hz,
1H), 8.53 (d, J = 8.0 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δC 109.8, 112.7, 114.4,
118.3, 120.8, 121.9, 122.0, 122.2, 122.6, 123.0, 123.3, 125.8, 126.49, 126.53, 127.3,
128.1, 128.5, 128.8, 129.6, 130.2, 131.5, 135.0, 138.1, 138.4, 140.7. IR (KBr):
ν
3053, 1705, 1609, 1575, 1552, 1509, 1488, 1456, 1419, 1401, 1356, 1320, 1253,
ACS Paragon Plus Environment

Page 9 of 18
The Journal of Organic Chemistry
1
2
3
4
5
1240, 1215, 1140, 1073, 872, 820, 790, 693, 657 cm-1. HRMS (TOF, ESI, m/z): Calcd
for C25H14ClN2 [M+H]+ 377.0846, found 377.0833.
6
7
8
[1,3]Dioxolo[4'',5'':4',5']benzo[1',2':7,8]benzo[1,2]quinolizino[3,4,5,6-kla]per
9
1
imidine (3c). Yield 72% (278 mg). Pale yellow solid, m.p. 240~242 °C; H NMR
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(CDCl3, 400 MHz): δH 6.18 (s, 2H), 7.46~7.50 (m, 1H), 7.63~7.67 (m, 2H), 7.71 (s,
1H), 7.91 (d, J = 8.8 Hz, 1H), 7.97 (s, 1H), 8.09~8.13 (m, 2H), 8.16 (d, J = 8.0 Hz,
1H), 8.21 (d, J = 8.8 Hz, 1H), 8.24 (d, J = 8.0 Hz, 1H), 8.43 (d, J = 8.0 Hz, 1H). 13C
NMR (CDCl3, 100 MHz): δC 102.4, 102.5, 104.9, 112.1, 118.2, 121.2, 122.2, 122.6,
122.8, 123.2, 123.7, 124.7, 127.3, 127.4, 127.8, 128.1, 128.8, 129.0, 129.5, 130.1,
133.5, 135.4, 140.6, 143.0, 147.1, 151.5. IR (KBr):
ν 2905, 1706, 1614, 1552, 1501,
1462, 1365, 1322, 1260, 1244, 1213, 1174, 1125, 1089, 1034, 935, 893, 821, 790,
754, 691 cm-1. HRMS (TOF, ESI, m/z): Calcd for C26H15N2O2 [M+H]+ 387.1134,
found 387.1135.
13-Fluorodibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine (3d). Yield 69%
(249 mg). Pale yellow solid, m.p. 280~282 °C (Lit.13 283~285 °C); 1H NMR (CDCl3,
400 MHz): δH 7.48~7.53 (m, 2H), 7.65~7.69 (m, 2H), 7.93~7.96 (m, 1H), 8.15~8.19
(m, 3H), 8.23~8.33 (m, 4H), 8.47 (d, J = 8.0 Hz, 1H). 13C NMR (CDCl3, 100 MHz):
δC 112.2 (d, J(F-C) = 24.0 Hz), 112.8, 118.2, 119.0 (d, J(F-C) = 24.0 Hz), 121.5, 122.5,
122.80, 122.82 (d, J(F-C) = 8.0 Hz), 123.1, 123.3, 124.9 (d, J(F-C) = 1.0 Hz), 127.2,
128.0, 128.3, 128.8, 129.5, 130.1, 133.4, 133.5, 135.10(d, J(F-C) = 17.0 Hz), 135.11,
140.5, 148.6, 160.1, 161.3 (d, J(F-C) = 243.0 Hz). IR (KBr):
ν 3053, 1792, 1705, 1615,
1573, 1542, 1508, 1473, 1424, 1363, 1321, 1276, 1200, 1122, 1091, 1027, 965, 851,
820, 789, 775, 753, 693 cm-1. HRMS (TOF, ESI, m/z): Calcd for C25H14FN2 [M+H]+
361.1142, found 361.1142.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 18
1
2
3
4
5
6
13-Methoxydibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine (3e). Yield
1
78% (290 mg). Pale yellow solid, m.p. 144~146 °C (Lit.13 140~141 °C); H NMR
7
8
(CDCl3, 400 MHz): δH 4.01 (s, 3H), 7.30~7.33 (m, 1H), 7.45~7.49 (m, 1H), 7.63~7.67
9
(m, 2H), 7.90 (d, J = 8.8 Hz, 1H), 8.11~8.15 (m, 4H), 8.19~8.24 (m, 3H), 8.42 (d, J =
7.6 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δC 56.0, 108.7, 112.8, 118.1, 119.5, 121.1,
122.0, 122.7, 122.7, 123.3, 123.8, 123.9, 127.0, 127.7, 127.9, 128.65, 128.73, 129.4,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
130.0, 130.5, 135.1, 135.5, 138.4, 140.5, 143.4, 158.8. IR (KBr):
ν 3044, 1772, 1701,
1613, 1558, 1509, 1478, 1457, 1433, 1364, 1322, 1290, 1238, 1214, 1143, 1125,
1105, 1062, 1031, 960, 819, 788, 775, 751, 693 cm-1. HRMS (TOF, ESI, m/z): Calcd
for C26H17N2O [M+H]+ 373.1342, found 373.1343.
12,13-Dimethoxydibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine
(3f).
1
Yield 71% (286 mg). Pale yellow solid, m.p. 229~231 °C; H NMR (CDCl3, 400
MHz): δH 4.09 (s, 3H), 4.10 (s, 3H), 7.48~7.51 (m, 1H), 7.65~7.69 (m, 2H), 7.78 (s,
1H), 7.93 (d, J = 8.8 Hz, 1H), 8.09 (s, 1H), 8.14~8.18 (m, 3H), 8.22~8.26 (m, 2H),
8.45 (d, J = 7.6 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δC 56.3, 56.5, 104.3, 106.9,
112.2, 118.2, 118.7, 118.8, 121.1, 122.1, 122.5, 123.2, 124.0, 124.3, 125.8, 127.3,
127.7, 128.0, 128.7, 129.4, 130.0, 131.8, 135.6, 140.6, 143.4, 148.6, 152.6. IR (KBr):
ν
2949, 1769, 1644, 1604, 1579, 1497, 1476, 1455, 1409, 1380, 1331, 1320, 1266,
1223, 1168, 1152, 1113, 1100, 1061, 1008, 824, 799, 768, 721 cm-1. HRMS (TOF,
ESI, m/z): Calcd for C27H19N2O2 [M+H]+ 403.1447, found 403.1446.
13-Chlorodibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine (3g). Yield 81%
1
(305 mg). Pale yellow solid, m.p. 222~224 °C; H NMR (CDCl3, 400 MHz): δH
7.47~7.51 (m, 1H), 7.64~7.71 (m, 3H), 7.89 (d, J = 8.8 Hz, 1H), 8.10 (d, J = 7.2 Hz,
2H), 8.12~8.20 (m, 3H), 8.23 (d, J = 8.0 Hz, 1H), 8.42 (d, J = 7.6 Hz, 1H), 8.55 (d, J
= 2.0 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δC 112.6, 118.1, 121.6, 122.3, 122.4,
ACS Paragon Plus Environment

Page 11 of 18
The Journal of Organic Chemistry
1
2
3
4
122.5, 123.0, 123.2, 125.1, 125.2, 126.9, 128.0, 128.3, 128.7, 128.8, 129.4, 129.5,
5
6
130.0, 131.5, 132.2, 134.5, 135.0, 135.2, 140.5, 141.9. IR (KBr):
ν 3047, 1630, 1601,
7
8
9
1542, 1507, 1492, 1456, 1417, 1403, 1338, 1271, 1245, 1165, 1105, 1070, 1030, 917,
815, 757, 690 cm-1. HRMS (TOF, ESI, m/z): Calcd for C25H14ClN2 [M+H]+ 377.0846,
found 377.0831.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
12-Fluorodibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine (3h). Yield 72%
1
(259 mg). Pale yellow solid, m.p. > 300 °C (Lit.13 298~300 °C); H NMR (CDCl3,
400 MHz): δH 7.31~7.36 (m, 1H), 7.49~7.53 (m, 1H), 7.66~7.70 (m, 2H), 7.93 (d, J =
8.8 Hz, 1H), 7.97~8.00 (m, 1H), 8.12~8.15 (m, 2H), 8.18 (d, J = 8.0 Hz, 1H) , 8.23 (d,
J = 9.2 Hz, 1H), 8.26 (d, J = 8.0 Hz, 1H), 8.46 (d, J = 7.6 Hz, 1H), 8.58~8.61 (m, 1H).
13C NMR (CDCl3, 100 MHz): δC 109.1 (d, J(F-C) = 26.0 Hz), 112.6, 113.8 (d, J(F-C)
=
24.0 Hz), 116.2, 118.2, 121.8, 122.5, 122.9, 123.3, 125.7, 126.5(d, J(F-C) = 9.0 Hz),
127.2, 128.1, 128.5, 128.8, 129.3 (d, J(F-C) = 3.0 Hz), 129.6, 130.2, 135.0, 137.4, 139.2
(d, J(F-C) = 11.0 Hz), 140.7, 142.4, 153.6, 165.2 (d, J(F-C) = 250.0 Hz). IR (KBr):
ν
3058, 1706, 1684, 1618, 1568, 1508, 1470, 1457, 1424, 1405, 1327, 1296, 1260,
1242, 1192, 1132, 1077, 1003, 892, 864, 837, 820, 791, 773, 753 cm-1. HRMS (TOF,
ESI, m/z): Calcd for C25H14FN2 [M+H]+ 361.1142, found 361.1143.
12-Methyldibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine (3i). Yield 73%
1
(260 mg). Pale yellow solid, m.p.129~131 °C (Lit.13 128~130 °C); H NMR (CDCl3,
400 MHz): δH 2.59 (s, 3H), 7.38 (d, J = 8.0 Hz, 1H), 7.46~7.50 (m, 1H), 7.64~7.68
(m, 2H), 7.87 (d, J = 8.8 Hz, 1H), 8.06 (s, 1H), 8.09~8.20 (m, 5H), 8.39~8.45 (m,
13
2H). C NMR (CDCl3, 100 MHz): δC 22.5, 112.7, 118.1, 121.3, 122.1, 122.4, 122.5,
123.2, 123.3, 124.6, 124.7, 126.9, 127.5, 127.7, 128.1, 128.8, 129.4, 130.0, 130.79,
130.83, 135.4, 137.5, 140.7, 142.6, 143.2, 148.2. IR (KBr):
ν 3025, 2924, 2845, 1648,
1632, 1611, 1587, 1508, 1496, 1475, 1447, 1390, 1370, 1262, 1211, 1179, 1152, 1100,
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 18
1
2
3
4
5
1010, 810, 749, 735, 705, 663, 635 cm-1. HRMS (TOF, ESI, m/z): Calcd for C26H17N2
[M+H]+ 357.1392, found 357.1399.
6
7
8
9
7-Ethoxydibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine (3j). Yield 77%
(298 mg). Pale yellow solid, m.p. 222~224 °C; 1H NMR (CDCl3, 400 MHz): δH 1.52
(t, J = 7.2 Hz, 3H), 4.20 (q, J = 7.2 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H), 7.62~7.66 (m,
1H), 7.78~7.82 (m, 1H), 7.94 (d, J = 9.2 Hz, 1H), 8.11~8.14 (m, 2H), 8.18 (d, J = 8.0
Hz, 1H), 8.23~8.27 (m, 2H), 8.36 (d, J = 8.0 Hz, 1H), 8.47 (d, J = 7.6 Hz, 1H), 8.66
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13
(d, J = 7.6 Hz, 1H). C NMR (CDCl3, 100 MHz): δC 14.9, 63.7, 111.0, 112.9, 114.2,
115.5, 115.6, 118.1, 121.3, 121.8, 122.1, 122.5, 123.4, 125.1, 125.2, 126.2, 127.7,
128.2, 130.1, 130.2, 131.7, 132.3, 133.3, 137.3, 140.9, 143.3, 158.9. IR (KBr):
ν
3054, 2925, 1678, 1599, 1508, 1475, 1420, 1392, 1248, 1172, 1115, 1042, 991, 943,
921, 822, 757, 691 cm-1. HRMS (TOF, ESI, m/z): Calcd for C27H19N2O [M+H]+
387.1498, found 387.1497.
13-Chloro-7-ethoxydibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine (3k).
1
Yield 80% (337 mg). Pale yellow solid, m.p. 225~227 °C; H NMR (CDCl3, 400
MHz): δH 1.52 (t, J = 7.2 Hz, 3H, CH3), 4.20 (q, J = 7.2 Hz, 2H, CH2), 7.19 (d, J = 8.8
Hz, 2H), 7.72~7.74 (m, 1H), 7.92 (d, J = 9.2 Hz, 1H), 8.07 (d, J = 8.8 Hz, 2H),
8.15~8.26 (m, 4H), 8.45 (d, J = 8.0 Hz, 1H), 8.60 (d, J = 2.0 Hz, 1H). 13C NMR
(CDCl3, 100 MHz): δC 14.9, 63.7, 112.8, 115.5, 118.1, 121.5, 122.1, 122.35, 122.42,
122.8, 123.3, 125.2, 125.7, 126.3, 127.3, 127.4, 128.37, 128.41, 130.1, 130.2, 131.6,
132.0, 134.5, 135.4, 137.7, 140.8, 159.1. IR (KBr):
ν 3049, 2977, 1635, 1604, 1577,
1522, 1508, 1476, 1458, 1395, 1372, 1280, 1247, 1173, 1138, 1153, 1073, 1043, 941,
922, 821, 795, 761, 693, 641 cm-1. HRMS (TOF, ESI, m/z): Calcd for C27H18ClN2O
[M+H]+ 421.1108, found 421.1107.
ACS Paragon Plus Environment

Page 13 of 18
The Journal of Organic Chemistry
1
2
3
4
5
6
7-Ethoxy-12,13-dimethoxydibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine
(3l). Yield 67% (299 mg). Pale yellow solid, m.p. 233~235 °C; 1H NMR (CDCl3, 400
7
8
MHz): δH 1.52 (t, J = 7.2 Hz, 3H), 4.10 (s, 3H), 4.12 (s, 3H), 4.20 (q, J = 7.2 Hz, 2H),
9
7.20 (d, J = 8.8 Hz, 2H), 7.79 (s, 1H), 7.93 (d, J = 8.8 Hz, 1H), 8.09~8.14 (m, 3H),
8.17 (d, J = 8.0 Hz, 1H), 8.22~8.26 (m, 2H), 8.45 (d, J = 8.0 Hz, 1H). 13C NMR
(CDCl3, 100 MHz): δC 14.9, 56.3, 56.5, 63.7, 112.3, 112.8, 115.2, 115.47, 115.54,
118.0, 118.9, 120.9, 121.4, 122.3, 122.6, 122.7, 122.8, 123.2, 123.4, 125.2, 127.4,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
128.0, 128.3, 129.9, 130.0, 131.9, 133.6, 152.7, 159.0. IR (KBr):
ν 3041, 2927, 1682,
1638, 1605, 1579, 1500, 1462, 1379, 1321, 1266, 1168, 1119, 1099, 1073, 1026, 942,
825, 767, 747, 703, 668 cm-1. HRMS (TOF, ESI, m/z): Calcd for C29H23N2O3 [M+H]+
447.1709, found 447.1705.
7-Ethoxy-[1,3]dioxolo[4'',5'':4',5']benzo[1',2':7,8]benzo[1,2]quinolizino[3,4,5
,6-kla]perimidine (3m). Yield 69% (297 mg). Pale yellow solid, m.p. 240~242 °C; 1H
NMR (CDCl3, 400 MHz): δH 1.52 (t, J = 7.2 Hz, 3H), 4.19 (q, J = 7.2 Hz, 2H), 6.21
(s, 2H), 7.19 (d, J = 8.8 Hz, 2H), 7.75 (s, 1H), 7.92 (d, J = 8.8 Hz, 1H), 8.00~8.07 (m,
3H), 8.14~8.26 (m, 3H), 8.45 (d, J = 7.6 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δC
14.9, 63.7, 102.2, 102.4, 104.8, 114.3, 114.7, 115.5, 117.9, 121.0, 122.0, 122.3, 123.2,
123.2, 125.0, 127.1, 127.7, 128.1, 130.0, 130.1, 130.6, 133.1, 133.5, 140.6, 142.9,
146.9, 151.4, 158.9. IR (KBr):
ν 3045, 2975, 1636, 1602, 1579, 1508, 1466, 1401,
1371, 1333, 1291, 1259, 1245, 1174, 1113, 1036, 928, 877, 822, 759, 720, 680 cm-1.
HRMS (TOF, ESI, m/z): Calcd for C28H19N2O3 [M+H]+ 431.1396, found 431.1381.
7-Ethoxy-12-fluorodibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine (3n).
1
Yield 73% (295 mg). Pale yellow solid, m.p. 276~278 °C; H NMR (CDCl3, 400
MHz): δH 1.53 (t, J = 6.8 Hz, 3H), 4.20 (q, J = 6.8 Hz, 2H), 7.19~7.22 (m, 2H),
7.30~7.35 (m, 1H), 7.93 (d, J = 8.8 Hz, 1H), 7.96~7.99 (m, 1H), 8.05~8.09 (m, 2H),
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 18
1
2
3
4
5
6
7
8
9
8.15~8.26 (m, 3H), 8.45 (d, J = 8.0 Hz, 1H), 8.59~8.62 (m, 1H). 13C NMR (CDCl3,
100 MHz): δC 14.9, 63.8, 108.9 (d, J(F-C) = 25.0 Hz), 112.6, 113.6 (d, J(F-C) = 24.0 Hz),
115.6, 115.7, 118.0, 121.6, 122.1, 122.3, 122.6, 123.3, 126.0, 126.5 (d, J(F-C) = 11.0
Hz), 127.4 (d, J(F-C) = 11.0 Hz), 128.4, 129.2 (d, J(F-C) = 2.0 Hz), 130.1, 130.3, 139.2,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
139.3, 140.9, 142.4, 159.1, 164.5, 165.2 (d, J(F-C) = 250.0 Hz). IR (KBr):
ν 3058,
2985, 2930, 1635, 1618, 1603, 1511, 1496, 1476, 1435, 1416, 1393, 1333, 1308,
1286, 1253, 1230, 1117, 1063, 1045, 989, 963, 945, 899, 870, 839, 801, 653 cm-1.
HRMS (TOF, ESI, m/z): Calcd for C27H18FN2O [M+H]+ 405.1404, found 405.1405.
13-Chloro-7-propyldibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine (3o).
1
Yield 80% (335 mg). Pale yellow solid, m.p. 241~243 °C; H NMR (CDCl3, 400
MHz): δH 1.06 (t, J = 7.2 Hz, 3H), 1.79 (q, J = 7.6 Hz, 2H), 2.75 (t, J = 7.6 Hz, 2H),
7.48 (d, J = 8.4 Hz, 2H), 7.71~7.74 (m, 1H), 7.92 (d, J = 8.8 Hz, 1H), 8.05 (d, J = 8.0
Hz, 2H), 8.14~8.18 (m, 1H), 8.21~8.26 (m, 3H), 8.45 (d, J = 7.6 Hz, 1H), 8.59 (d, J =
2.0 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δC 14.0, 24.6, 38.0, 112.7, 118.2, 121.5,
122.2, 122.4, 122.5, 122.9, 123.4, 125.1, 125.6, 127.1, 128.3, 128.4, 128.7, 128.8,
129.6, 130.1, 131.5, 132.1, 132.4, 134.5, 135.4, 140.6, 142.0, 142.9. IR (KBr):
ν
3053, 2956, 2928, 1602, 1507, 1484, 1448, 1417, 1362, 1266, 1177, 1114, 1075, 941,
880, 818, 793, 755, 692 cm-1. HRMS (TOF, ESI, m/z): Calcd for C28H20ClN2 [M+H]+
419.1316, found 419.1322.
7-Methoxydibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine (3p). Yield 75%
(279 mg). Pale yellow solid, m.p. 220~222 °C; 1H NMR (CDCl3, 400 MHz): δH 3.95
(s, 3H), 7.17 (d, J = 8.4 Hz, 2H), 7.55~7.59 (m, 1H), 7.71~7.74 (m, 1H), 7.84 (d, J =
9.2 Hz, 1H), 8.06 (d, J = 8.8 Hz, 2H), 8.09~8.19 (m, 3H), 8.25 (d, J = 8.0 Hz, 1H),
8.41 (d, J = 7.6 Hz, 1H), 8.58 (d, J = 7.6 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δC
55.5, 112.7, 114.9, 117.9, 121.2, 121.7, 122.0, 122.4, 122.8, 123.2, 124.9, 125.0,
ACS Paragon Plus Environment

Page 15 of 18
The Journal of Organic Chemistry
1
2
3
4
126.1, 127.0, 127.8, 128.1, 130.0, 130.1, 131.6, 131.8, 133.2, 137.2, 140.7, 143.0,
5
6
143.8, 159.4. IR (KBr):
ν 3011, 2917, 1608, 1548, 1523, 1507, 1474, 1462, 1427,
7
8
9
1393, 1366, 1326, 1293, 1252, 1173, 1112, 1025, 842, 820, 788, 754, 709, 692, 658,
618 cm-1. HRMS (TOF, ESI, m/z): Calcd for C26H17N2O [M+H]+ 373.1342, found
373.1347.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
13-Chloro-7-methoxydibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine
(3q). Yield 78% (317 mg). Pale yellow solid, m.p. 225~227 °C; 1H NMR (CDCl3, 400
MHz): δH 3.96 (s, 3H), 7.16 (d, J = 8.8 Hz, 2H), 7.63~7.66 (m, 1H), 7.82 (d, J = 8.8
Hz, 1H), 7.98 (d, J = 8.8 Hz, 2H), 8.08~8.12 (m, 3H), 8.17 (d, J = 7.6 Hz, 1H), 8.37
(d, J = 8.0 Hz, 1H), 8.49 (d, J = 1.6 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δC 55.5,
112.6, 115.0, 117.9, 121.4, 121.8, 122.2, 122.3, 122.8, 123.2, 123.5, 125.1, 125.4,
127.0, 127.5, 128.3, 130.0, 130.1, 131.4, 131.9, 134.3, 135.2, 140.6, 141.8, 142.7,
159.6. IR (KBr):
ν 3067, 1723, 1636, 1604, 1577, 1509, 1459, 1440, 1395, 1375,
1321, 1279, 1250, 1205, 1182, 1138, 1107, 1075, 1057, 1027, 940, 877, 830, 794, 761
cm-1. HRMS (TOF, ESI, m/z): Calcd for C26H16ClN2O [M+H]+ 407.0951, found
407.0945.
7-Chlorodibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine (3r). Yield 76%
1
(286 mg). Pale yellow solid, m.p. 223~225 °C; H NMR (CDCl3, 400 MHz): δH
7.61~7.65 (m, 3H), 7.76~7.80 (m, 1H), 7.91 (d, J = 8.8 Hz, 1H), 8.07 (d, J = 8.4 Hz,
2H), 8.13~8.17 (m, 2H), 8.23~8.27 (m, 2H), 8.45 (d, J = 7.6 Hz, 1H), 8.62 (d, J = 7.6
Hz, 1H). 13C NMR (CDCl3, 100 MHz): δC 104.9, 112.7, 118.0, 121.6, 121.8, 122.5,
122.87, 122.92, 123.4, 123.5, 123.6, 125.2, 126.6, 126.9, 128.3, 129.6, 129.9, 130.0,
131.8, 133.3, 133.6, 133.8, 136.9, 140.6, 143.1. IR (KBr):
ν 3239, 1636, 1616, 1588,
1521, 1516, 1507, 1488, 1473, 1418, 1396, 1349, 1091, 835, 787, 757, 701, 668 cm-1.
HRMS (TOF, ESI, m/z): Calcd for C25H14ClN2 [M+H]+ 377.0846, found 377.0841.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 18
1
2
3
4
5
6
7-Chloro-13-methoxydibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine (3s).
1
Yield 80 % (325 mg). Pale yellow solid, m.p. 238~240 °C; H NMR (CDCl3, 400
7
8
9
MHz): δH 4.04 (s, 3H), 7.34~7.37 (m, 1H), 7.62 (d, J = 8.4 Hz, 2H), 7.94 (d, J = 8.8
Hz, 1H), 8.09 (d, J = 8.0 Hz, 2H), 8.14~8.21 (m, 4H), 8.27 (d, J = 7.6 Hz, 1H), 8.46
(d, J = 8.0 Hz, 1H). 13C NMR (CDCl3, 100 MHz): δC 56.0, 108.9, 109.9, 112.8, 118.0,
119.6, 121.3, 122.3, 122.5, 122.6, 122.9, 123.0, 127.05, 127.06, 128.1, 128.2, 129.6,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
129.7, 130.00, 130.02, 130.3, 133.5, 134.1, 135.1, 140.5, 159.0. IR (KBr):
ν 3239,
1771, 1733, 1637, 1616, 1583, 1558, 1540, 1507, 1478, 1434l, 1289, 1236, 1213,
1124, 1092, 1062, 851, 820, 810, 786, 708, 668 cm-1. HRMS (TOF, ESI, m/z): Calcd
for C26H16ClN2O [M+H]+ 407.0952, found 407.0958.
13-Chloro-6-fluorodibenzo[1,2:7,8]quinolizino[3,4,5,6-kla]perimidine
(3t).
1
Yield 77% (304 mg). Pale yellow solid, m.p. 234~236 °C; H NMR (CDCl3, 400
MHz): δH 7.17~7.22 (m, 1H), 7.60~7.62 (m, 1H), 7.74~7.77 (m, 1H), 7.79~7.82 (m,
1H), 7.91 (d, J = 7.6 Hz, 1H), 7.95 (d, J =8.8 Hz, 1H), 8.16~8.23 (m, 3H), 8.28 (d, J =
7.6 Hz, 1H), 8.47 (d, J = 8.0 Hz, 1H), 8.60 (d, J = 2.0 Hz, 1H). 13C NMR (CDCl3, 100
MHz): δC 112.7, 114.8 (d, J(F-C) = 21.0 Hz), 115.4 (d, J(F-C) = 22.0 Hz), 118.2, 122.0,
122.6, 122.8, 122.9 (d, J(F-C) = 8.0 Hz), 123.4, 124.4 (d, J(F-C) = 3.0 Hz), 124.5, 125.3,
127.0, 128.5, 130.1, 131.1 (d, J(F-C) = 8.0 Hz), 131.8, 132.6, 134.6, 135.1, 137.25,
137.33, 140.5, 142.1, 163.5 (d, J(F-C) = 245.0 Hz). IR (KBr):
ν 3071, 1685, 1635,
1616, 1600, 1561, 1492, 1470, 1441, 1380, 1342, 1302, 1269, 1239, 1189, 1154,
1106, 1026, 918, 880, 868, 866, 796, 763, 731, 695 cm-1. HRMS (TOF, ESI, m/z):
Calcd for C25H13ClFN2 [M+H]+ 395.0752, found 395.0744.
13-(4-nitrophenyl)isoquinolino[2,1-a]perimidine (4u). Yield 88% (343 mg).
1
Red solid, m.p. 227~229 °C; H NMR (CDCl3, 400 MHz): δH 5.48 (d, J = 7.6 Hz,
1H), 6.88~6.92 (m, 1H), 7.00 (s, 1H), 7.05 (d, J = 8.4 Hz, 2H), 7.32 (d, J = 8.0 Hz,
ACS Paragon Plus Environment

Page 17 of 18
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
1H), 7.42~7.44 (m, 1H), 7.51~7.54 (m, 2H), 7.60~7.66 (m, 1H), 7.69~7.74 (m, 1H),
7.96 (d, J = 8.0 Hz, 1H), 8.10 (d, J = 8.8 Hz, 2H), 8.22 (d, J = 7.6 Hz, 1H). 13C NMR
(CDCl3, 100 MHz): δC 104.5, 111.4, 119.3, 119.7, 120.1, 121.4, 122.7, 122.9, 123.4,
124.1, 125.6, 128.1, 129.1, 129.7, 130.5, 131.1, 132.0, 134.4, 135.7, 138.5, 141.0,
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
145.6, 152.9. IR (KBr):
ν 3053, 1640, 1622, 1573, 1517, 1508, 1474, 1378, 1341,
1222, 1181, 1104, 1060, 872, 825, 774, 755, 688 cm-1. HRMS (TOF, ESI, m/z): Calcd
for C25H16N3O2 [M+H]+ 390.1243, found 390.1255.
Acknowledgements: We are grateful to the Major Natural Science Foundation of
Jiangsu Province (14KJA150004), a project funded by the Priority Academic Program
Development of Jiangsu Higher Education Institutions of Jiangsu Province for
financial support.
Supporting Information Available: Data and copies of H NMR, 13C NMR spectra
1
for compounds 3a-3t, 4a, 4u and 5k are available free of charge via the internet at
http://pubs.acs.org.
References
(1) (a) Ashenhurst, J. A. Chem. Soc. Rev. 2010, 39, 540-548. (b) Chen, X.; Engle, K.; Wang, D. H.;
Yu, J. Q. Angew. Chem., Int. Ed. 2009, 48, 5094-5115. (c) Ackermann, L.; Vicente, R.; Kapdi, A.
R. Angew. Chem., Int. Ed. 2009, 48, 9792-9826.
(2) (a) Li, H.; Liu, J.; Sun, C. L.; Li, B. J.; Shi, Z. J. Org. Lett. 2011, 13, 276-279. (b) Pintori D. G.;
Greaney, M. F. J. Am. Chem. Soc. 2011, 133, 1209-1211. (c) Jiao, L.; Smirnov, P.; Oestreich, M.
Org. Lett. 2014, 16, 6020-6023.
(3) Trosien, S.; Böttger, P.; Waldvogel. S. R. Org. Lett. 2014, 16, 402-405.
(4) Itoh, M.; Hirano, K.; Satoh, T.; Shibata, Y.; Tanaka, K.; Miura M. J. Org. Chem. 2013, 78,
1365-1370.
(5) Dong, J.; Long, D.; Song, F.; Wu, N.; Guo, Q.; Lan, J.; You, J. Angew. Chem., Int. Ed. 2013, 52,
580-584.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 18
1
2
3
4
5
6
7
(6) (a) Laha, J. K. ; Jethava, K. P.; Dayal, N. J. Org. Chem. 2014, 79, 8010-8019. (b) Li, H.; Zhu,
R. Y.; Shi, W. J.; He, K. H.; Shi, Z. J. Org. Lett. 2012, 14, 4850-4853. (c) Chen, X.; Huang, X.; He,
Q.; Xie, Y.; Yang C. Chem. Commun. 2014, 50, 3996-3999.
8
9
(7) (a)Y ang, F.; Song, F.; Li, W.; Lan J.; You J. RSC Adv. 2013, 3, 9649-9652. (b) Storr, T. E.;
Namata, F.; Greaney, M. F. Chem. Commun. 2014, 50, 13275-13277.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(8) Chandrasekharam, M;. Chiranjeevi, B.; Gupta, K. S. V.; Sridhar B. J. Org. Chem. 2011, 76,
10229-10235.
(9) (a) Pintori, D. G.; Greaney M. F. Org. Lett. 2011, 13, 5713-5715. (b) Li, N.; Zhang, Y.; Mao, S.;
Gao, Y.; Guo, D.; Wang, Y. Org. Lett. 2014, 16, 2732-2735. (c) Pintori D. G.; Greaney, M. F. Org.
Lett. 2011, 13, 5713–5715.
(10) (a) Bunescu, A.; Piou, T.; Wang, Q.; Zhu, J. Org. Lett. 2015, 17, 334-337. (b) Ackermann, L.;
Jeyachandran, R.; Potukuchi, H. K.; Novak, P.; Buttner, L. Org. Lett. 2010, 12, 2056-2059.
(11) (a) Mao, Z.; Wang, Z.; Xu, Z.; Huang, F.; Yu, Z.; Wang, R. Org. Lett. 2012, 14, 3854-3857. (b)
Odani, R.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2015, 80, 2384-2391. (c) Odani, R.;
Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2013, 78, 11045-11052.
(12) Laali, K. K. Chem. Rev. 1996, 96, 1873-1906.
(13) Tokimizu, Y.; Ohta, Y.; Chiba, H.; Oishi, S.; Fujii, N.; Ohno, H. Tetrahedron 2011, 67,
5168-5175.
(14) (a) King, A. E.; Brunold, T. C.; Stahl, S. S. J. Am. Chem. Soc. 2009, 131, 5044-5045. (b) King,
A. E.; Huffman, L. M.; Casitas, A.; Costas, M.; Ribas, X.; Stahl, S. S. J. Am. Chem. Soc. 2010,
132, 12068-12073. (c) Chen, Q. A.; Wang, D. S.; Zhou, Y.G.; Duan, Y.; Fan, H. J.; Yang, Y.; Zhang,
Z. J. Am. Chem. Soc. 2011, 133, 6126-6129.
(15) (a) Chen, D. S.; Dou, G. L.; Li, Y. L.; Liu, Y.; Wang, X. S. J. Org. Chem. 2013, 78, 5700-5704.
(b) Li, C.; Zhang, W. T.; Wang, X. S. J. Org. Chem. 2014, 79, 5847-5851.
(16) (a) Huffman, L. M and Stahl, S. S. J. Am. Chem. Soc. 2008, 130, 9196-9197. (b) Ackermann,
L. Chem. Rev. 2011, 111, 1315-1345. (c) Grzybowski, M.; Skonieczny, K.; Butenschön, H.; Gryko,
D. T. Angew. Chem., Int. Ed. 2013, 52, 9900-9930. (d) Ni, Z.; Zhang, Q.; Xiong, T.; Zheng, Y.; Li,
Y.; Zhang, H.; Zhang, J.; Liu, Q. Angew. Chem., Int. Ed. 2012, 51, 1244-1247.
ACS Paragon Plus Environment