Manganese(III) acetate mediated oxidative radical cyclizations of N -(2-alkenylaryl)-substituted enamines

Article abstract of DOI:10.1055/s-0033-1338561

A method has been developed for the synthesis of highly functionalized quinolines from readily available N-(2-alkenylaryl)-substituted enamines via a 6-exo-trig radical cyclization of an imine radical. Several useful functional groups including morpholinocarbonyl, benzoyl, and cyano, are compatible with the reaction conditions. Under the Mn(II)/Co(II)/O₂ redox system, these N-(2-alkenylaryl)enamines were also converted into the corresponding quinolines effectively. This strategy was further applied to related 1,4-naphthoquinone derivatives, and benzo[b]acridine-6,11-diones were formed in good yields.

Full text of DOI:10.1055/s-0033-1338561

PAPER
▌175
paper
Manganese(III) Acetate Mediated Oxidative Radical Cyclizations of
N-(2-Alkenylaryl)-Substituted Enamines
Oxidative Radical Cyclizations of N-(2-Alkenylaryl)-Substituted Enamines
Pei-Ju Tsai, Chih-Bo Kao, Wan-Ru Chiow, Che-Ping Chuang*
Department of Chemistry, National Cheng Kung University, Tainan, 70101, Taiwan
Fax +886(6)2740552; E-mail: cpchuang@mail.ncku.edu.tw
Received: 01.09.2013; Accepted after revision: 25.10.2013
Imine radicals 2 can be generated effectively by the oxi-
dation of enamines 1 with metal salts (Scheme 1) and they
undergo efficient addition to C=C bonds.16 We describe
here a more effective method for the synthesis of highly
Abstract: A method has been developed for the synthesis of highly
functionalized quinolines from readily available N-(2-alkenylaryl)-
substituted enamines via a 6-exo-trig radical cyclization of an imine
radical. Several useful functional groups including morpholinocar-
bonyl, benzoyl, and cyano, are compatible with the reaction condi- functionalized quinolines via the manganese(III)-mediat-
tions. Under the Mn(II)/Co(II)/O2 redox system, these N-(2-
alkenylaryl)enamines were also converted into the corresponding
quinolines effectively. This strategy was further applied to related
ed oxidative radical cyclization reaction of enamines.
NR
O
NHR
O
Mn(III)
1,4-naphthoquinone derivatives, and benzo[b]acridine-6,11-diones
were formed in good yields.
R1
R2
R1
R2
or Ce(IV)
Key words: manganese(III) acetate, oxidative, free radical, en-
amines, quinolines
1
2
Scheme 1
Addition reactions of carbon-centered radicals to alkenes
are versatile tools for the formation of carbon–carbon
bonds, and many new methods that use radical reactions
in organic synthesis have been developed.1,2 During the
last three decades, metal salt mediated oxidative free rad-
ical reactions have been extensively explored, and they
have become increasingly important in the synthesis of
useful and complex molecules. Among these, manga-
nese(III) acetate and cerium(IV) ammonium nitrate
(CAN) have been used most efficiently.2–5
Our studies commenced with the readily available N-(2-
alkenylaryl)enamine carboxamide 3a, which was
prepared by the condensation of 1-morpholino-3-phenyl-
propane-1,3-dione with (E)-2-(2-phenylethenyl)phenyl-
amine (see Supporting Information). With enamine 3a in
hand, we examined the radical reaction of 3a with manga-
nese(III) acetate under various reaction conditions
(Scheme 2, Table 1). When the reaction of 3a and manga-
nese(III) acetate (4 equiv) was carried out in acetic acid at
room temperature under air for one hour, the target cycli-
zation product 4a was obtained in 58% yield (entry 1). It
is noteworthy that under an oxygen atmosphere instead of
air the yield improved to 78% (entry 2). When a catalytic
amount (0.3 equiv) of manganese(III) acetate was used, it
resulted mainly in the decomposition of 3a and a pro-
longed reaction time was required; the desired product 4a
was formed in 14% yield after stirring at room tempera-
ture for five hours (entry 3). Under a nitrogen atmosphere,
the reaction was slow with an unsatisfactory yield (25%),
confirming the necessity for molecular oxygen in this re-
action (entry 4). In an attempt to investigate the range of
solvents compatible with this reaction, the reaction be-
tween 3a and manganese(III) acetate was next performed
in various solvents. In acetonitrile, 4a was obtained in
good yield (80%), however, the reaction was sluggish and
required one hour at 80 °C to go to completion (entry 5).
Quinolines and their derivatives are known to possess a
wide range of biological activity and they have pharmaco-
logical properties that includes antimalarial,6 antibacteri-
al,7 anti-inflammatory,8 anticancer,9 anti-asthmatic,10
anti-alzheimer,11 and anti-HIV.12 As a result of the re-
markable importance of this class of heterocyclic com-
pound, a large number of methodologies have been
developed for the syntheses of functionalized quinolines,
such as Skraup, Doebner–von Miller, Friedländer, and
Combes synthesis.13 However, most of these methods re-
quire high temperatures or harsh reaction conditions, they
give the products in low yields, and they have problems
associated with the low stability of carbonyl reagents.
Some of these drawbacks have been overcome by the use
of more efficient methods such as modified Friedländer
strategies14 and transition-metal-catalyzed reactions.15
The development of mild and simple approaches to quin-
oline derivatives represents a challenge in organic and
medical chemistry.
Ph
R1
Mn(OAc)3, O2
R3
R3
HN
R2
N
R1
3
4
R2
SYNTHESIS 2014, 46, 0175–0182
Advanced online publication: 28.11.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
Scheme 2
DOI: 10.1055/s-0033-1338561; Art ID: SS-2013-F0596-OP
© Georg Thieme Verlag Stuttgart · New York

176
P.-J. Tsai et al.
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Ph
Ph
Ph
– Mn(II)
Mn(III)
Mn(III)
O
N
O
N
O
HN
5a
6a
3a
N
Ph
N
Ph
N
Ph
O
O
O
Ph
Ph
O
O
N
6-exo
N
O2
O
O
Ph
N
Ph
N
7a
8a
Ph
O
Ph
H
O
O
O
OH
O
O
– PhCHO
N
N
N
O
O
O
Ph
N
Ph
N
Ph
N
10a
9a
4a
Scheme 3
In 2,2,2-trifluoroethanol, formic acid, and chloroform, the 10a, formed by intramolecular hydrogen atom abstraction
desired product 4a was produced in much lower yields in 9a, undergoes fragmentation to produce quinoline 4a
(entries 6–8).
and benzaldehyde.17a
Using the optimal reaction conditions (Table 1, entry 2),
we explored the scope and limitations of this newly devel-
oped manganese(III)/oxygen/acetic acid method (Table 2,
entries 1–14, method A). By varying substituents R1 of
enamines 3, it was shown that several useful functional
groups, including morpholinocarbonyl, cyano, and benzo-
yl, were tolerated under the reaction conditions and the
expected quinolines 4 were formed effectively. To our de-
light, when R2 was an alkyl substituent, the desired oxida-
tive cyclization products 4l–n were also obtained in
acceptable yields (entries 12–14). Substrates bearing dif-
ferent functional groups (R3) on the aniline moiety in the
substrate, including 4-methyl, 2,4-dimethyl, 4,5-dimeth-
yl, and 4-chloro, all worked well in moderate to good
yields.
Table 1 Optimization of Reaction Conditions with N-(2-Alkenyla-
ryl)enamine 3a
Entry Solvent
Atmosphere Temp
(°C)
Time
(h)
Yielda
(%) of 4a
1
2
3
4
5
6
7
8
AcOH
air
O2
O2
N2
O2
O2
O2
O2
r.t.
r.t.
r.t.
r.t.
80
80
r.t.
80
1
58
78
14b
25
80
56
26
18
AcOH
0.5
5
AcOH
AcOH
1.5
1
MeCN
CF3CH2OH
HCO2H
CHCl3
1
0.5
1
A carbon radical is produced by the Mn(II)/Co(II)/oxygen
redox system and it undergoes efficient addition to a C=C
bond.18 In this reaction, Mn(II) can be continuously reox-
idized to Mn(III) by the action of a Co(III)–dioxygen
complex generated in situ from Co(II) and oxygen and a
catalytic amount of Mn(II) is used. Environmental con-
cerns have encourage the development of greener reaction
conditions. We have continued to study the radical cycli-
zation of reaction of N-(2-alkenylaryl)-substituted en-
amines 3 under the Mn(II)/Co(II)/O2 redox system.
a Yield of isolated product.
b Mn(OAc)3 (0.3 equiv) was used.
Since dioxygen plays an important role in this reaction, a
plausible reaction mechanism for the formation of 4a is
proposed (Scheme 3). Initiation occurs with the chelation
of manganese(III) acetate by the enamine nitrogen of 3a
to produce Mn(III) complex 5a. Subsequently, homolytic
cleavage of Mn(III) complex 5a takes place to generate
imine radical 7a and manganese(II) acetate. This resulting
radical intermediate 7a undergoes a 6-exo-trig cyclization
to give radical 8a, which is then trapped by oxygen to give
peroxy radical intermediate 9a. Finally, hydroperoxide
When N-(2-alkenylaryl)enamine carboxamide 3a was
treated with manganese(II) acetate (0.3 equiv) and co-
balt(II) acetate (1 equiv) in acetic acid at 80 °C under an
oxygen atmosphere (method B), the target cyclization
product 4a was obtained in 74% yield (Table 2, entry 15).
Synthesis 2014, 46, 175–182
© Georg Thieme Verlag Stuttgart · New York

PAPER
Oxidative Radical Cyclizations of N-(2-Alkenylaryl)-Substituted Enamines
177
By increasing the amount cobalt (II) acetate (1.5 equiv), aryl)amino]-1,4-naphthoquinones 11 were readily avail-
the yield can be improved to 84% (entry 16). Analogous able from the copper(II) acetate catalyzed addition of (E)-
results were obtained with other enamines 3 (entries 17– 2-(2-phenylethenyl)phenylamine to 1,4-naphthoquinone
26). In all cases, quinolines 4 were produced in a better (see Supporting Information). Indeed, when the reaction
reaction yield than those performed with manganese(III) of 2-[(2-alkenylaryl)amino]-1,4-naphthoquinone 11a and
acetate (method A).
manganese(III) acetate (Method A) was carried out in ace-
tic acid at room temperature under an oxygen atmosphere
for nine hours, the target cyclization product 12a was ob-
tained in 26% (Table 3, entry 2). The yield can be im-
proved to 86% by using formic acid as solvent instead of
acetic acid and reaction time was shorten to 30 minutes
(entry 5). Performing the reaction in acetonitrile with
Stimulated by the structural analogy of 2-(arylamino)-1,4-
naphthoquinones with enamino carbonyl compounds, the
manganese(III)-mediated radical cyclizations of 2-[(2-al-
kenylaryl)amino]-1,4-naphthoquinones 11 could be
envisioned to occur (Scheme 4). These 2-[(2-alkenyl-
Table 2 Reactions of N-(Alk-2-enylaryl)enamines 3
Entry
3
R1
R2
R3
Methoda
Product
Yieldb (%)
1
2
3a
3b
3c
3d
3e
3f
CO[N(CH2CH2)2O]
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
Me
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
H
A
A
A
A
A
A
A
A
A
A
A
A
A
A
Bc
B
B
B
B
B
B
B
B
B
B
B
4a
4b
4c
4d
4e
4f
78
80
78
77
81
80
75
78
78
83
82
64
75
57
74
84
90
89
86
86
87
86
85
87
85
92
CO[N(CH2CH2)2O]
4-Me
2,4-Me2
4,5-Me2
4-Cl
H
3
CO[N(CH2CH2)2O]
4
CO[N(CH2CH2)2O]
5
CO[N(CH2CH2)2O]
6
COPh
7
3g
3h
3i
COPh
4-Me
4-Cl
H
4g
4h
4i
8
COPh
9
CN
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
3j
CN
4-Me
4-Cl
H
4j
3k
3l
CN
4k
4l
COPh
3m
3n
3a
3a
3b
3c
3d
3e
3f
COPh
4-Me
4-Cl
H
4m
4n
4a
4a
4b
4c
4d
4e
4f
COPh
CO[N(CH2CH2)2O]
CO[N(CH2CH2)2O]
CO[N(CH2CH2)2O]
CO[N(CH2CH2)2O]
CO[N(CH2CH2)2O]
CO[N(CH2CH2)2O]
COPh
H
4-Me
2,4-Me2
4,5-Me2
4-Cl
H
3g
3h
3i
COPh
4-Me
4-Cl
H
4g
4h
4i
COPh
CN
3j
CN
4-Me
4-Cl
4j
3k
CN
3k
a Method A: Mn(OAc)3 (4 equiv), AcOH, r.t., O2 atmosphere; Method B: Mn(OAc)2 (0.3 equiv), Co(OAc)2 (1.5 equiv), AcOH (5 mL), 80 °C,
O2 atmosphere.
b Yield of isolated product.
c Co(OAc)2 (1 equiv) was used.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 175–182

178
P.-J. Tsai et al.
PAPER
formed by the radical cyclization of an imine radical19 13a
via a similar reaction route to that shown in Scheme 3. As
listed in Table 4, a variety of 2-[(2-alkenylaryl)amino]-
1,4-naphthoquinones 11 were evaluated to explore the
scope of this oxidative radical cyclization reaction under
the Mn(III)/oxygen/formic acid conditions. The results
demonstrated that the electronic properties of arylic sub-
stituents (R1) at the terminal of C=C bond affected the re-
action to some extent; electron-donating groups, such as
methyl or methoxy group, gave 12a in 91–93% yield (en-
tries 5 and 6), but electron-withdrawing groups, such as
chloro or cyano group, gave 12a in lower yields (entries 7
and 8). However, regardless of R2 on the aniline moiety,
electron-donating or electron-withdrawing, the oxidative
cyclization products 11b–d were obtained in good yields
(entries 2–4). The radical cyclization of reaction of 11 was
also conducted using the Mn(II)/Co(II)/O2 redox system.
As shown in Table 4 (entries 9–12), benzo[b]acridine-
6,11-diones 12 were also formed effectively by this
Mn(II)/Co(II)/O2 method.
Table 3 Optimization of Reaction Conditions with 2-(2-Alkenyl-
arylamino)-1,4-naphthoquinone 11a
Entry Solvent
Atmosphere Temp
(°C)
Time Yielda (%)
(h)
of 12a
1
2
3
4
5
6
AcOH
AcOH
AcOH
HCO2H
HCO2H
MeCN
air
O2
O2
O2
O2
air
45
r.t.
45
45
r.t.
80
3
24
26
29
82
86
0b
9
1
0.5
0.5
2
a Yield of isolated product.
b Starting 9a (88%) was recovered.
R1
O
O
R2
R2
Mn(OAc)3, O2
In conclusion, the syntheses of highly functionalized
quinolines and benzo[b]acridine-6,11-diones are de-
scribed. Imine radicals 7 can be produced by the manga-
nese(III) acetate oxidation of N-(2-alkenylaryl)enamines
and undergo a 6-exo-trig cyclization onto the C=C bond
efficiently. This reaction provides a synthetically useful
method for the synthesis of 2,3-disubstituted quinolines.
A variety of functional groups, including cyano, morpho-
linocarbonyl, and benzoyl, are compatible with the reac-
tion conditions. The traditional harshly basic or acidic
conditions can be avoided. Under Mn(II)/Co(II)/O2 redox
system, these N-(2-alkenylaryl)enamines were also con-
verted into the corresponding quinolines effectively. This
strategy was further applied for related 1,4-naphthoqui-
N
H
N
O
O
11
O
12
Ph
N
O
13a
Scheme 4
heating at 80 °C for two hours resulted in the recovery of
starting 11a (88%) only, and the desired 12a was not
formed (entry 6). Benzo[b]acridine-6,11-dione (12a) was
Table 4 Reactions of 2-(2-Alkenylarylamino)-1,4-naphthoquinones 11
Entry
Substrate
R1
R2
Method
Product
Yieldb (%)
1
2
11a
11b
11c
11d
11e
11f
Ph
H
A
A
A
A
A
A
A
B
B
B
B
B
12a
12b
12c
12d
12a
12a
12a
12a
12a
12b
12c
12d
86
Ph
4-Me
2,4-Me2
4-Cl
H
90
3
Ph
91
4
Ph
90
5
4-MeC6H4
4-MeOC6H4
4-ClC6H4
4-NCC6H4
Ph
91
6
H
9317b
82
7
11g
11h
11a
11b
11c
11d
H
8
H
8017c
75
9
H
10
11
12
Ph
4-Me
2,4-Me2
4-Cl
78
Ph
75
Ph
75
a Method A: Mn(OAc)3 (4 equiv), HCO2H, r.t., O2 atmosphere; Method B: Mn(OAc)2 (0.3 equiv), Co(OAc)2 (1.5 equiv), AcOH (5 mL), 80 °C,
O2 atmosphere.
b Yield of isolated product.
Synthesis 2014, 46, 175–182
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PAPER
Oxidative Radical Cyclizations of N-(2-Alkenylaryl)-Substituted Enamines
179
13C NMR (100.6 MHz, CDCl3): δ = 21.6 (q), 42.0 (t), 46.8 (t), 65.7
(t), 65.9 (t), 126.32 (s), 126.36 (d), 128.6 (2 d), 128.8 (s), 129.0 (2
d), 129.2 (d), 129.3 (d), 133.1 (d), 135.8 (d), 137.3 (s), 139.3 (s),
146.7 (s), 154.1 (s), 168.7 (s).
none derivatives, and benzo[b]acridine-6,11-diones were
formed in good yields.
Melting points are uncorrected. IR spectra were taken with a Hitachi
260-30 spectrophotometer. 1H and 13C NMR spectra were recorded
on a Bruker AMX-400 spectrometer with TMS as internal refer-
ence. The multiplicity of the 13C NMR signals was determined by
DEPT 135 experiments. Elemental analyses were performed with a
Heraeus CHN-Rapid Analyzer. Mass spectra were recorded on a
Jeol JMS-SX 102A mass spectrometer. Analytical TLC was per-
formed with precoated silica gel 60 F-254 plates (0.25-mm thick)
from EM Laboratories and visualized by UV. The reaction mixture
was purified by column chromatography over EM Laboratories sil-
ica gel (70–230 mesh).
Anal. Calcd for C21H20N2O2: C, 75.88; H, 6.06; N, 8.43. Found: C,
75.94; H, 6.13; N, 8.43.
6,8-Dimethyl-3-(morpholinocarbonyl)-2-phenylquinoline (4c)
Colorless needles; yield: 93 mg (78%) (method A), 72 mg (89%)
(method B); mp 190–191 °C.
IR (KBr): 2855, 1615, 1110, 775, 695 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.48 (ddd, J = 11.3, 8.0, 3.2 Hz, 1
H, CH), 2.51 (s, 3 H, CH3), 2.68 (ddd, J = 13.2, 5.0, 3.2 Hz, 1 H,
CH), 2.82 (s, 3 H, CH3), 2.92 (ddd, J = 13.2, 8.0, 3.2 Hz, 1 H, CH),
3.22 (ddd, J = 11.3, 5.0, 3.2 Hz, 1 H, CH), 3.36 (ddd, J = 11.3, 8.0,
3.2 Hz, 1 H, CH), 3.54 (ddd, J = 13.2, 8.0, 3.2 Hz, 1 H, CH), 3.64
(ddd, J = 11.3, 5.0, 3.2 Hz, 1 H, CH), 3.80 (ddd, J = 13.2, 5.0, 3.2
Hz, 1 H, CH), 7.44–7.53 (m, 5 H, HAr), 7.88–7.96 (m, 2 H, HAr),
8.14 (s, 1 H, HAr).
13C NMR (100.6 MHz, CDCl3): δ = 17.7 (q), 21.6 (q), 42.0 (t), 46.9
(t), 65.7 (t), 66.0 (t), 124.3 (d), 126.4 (s), 128.3 (s), 128.6 (2 d),
129.3 (3 d), 133.1 (d), 136.1 (d), 137.0 (s), 137.2 (s), 139.7 (s),
145.8 (s), 152.6 (s), 169.2 (s).
3-(Morpholinocarbonyl)-2-phenylquinoline (4a); Typical Pro-
cedure
Method A:
A mixture of 3a (103 mg, 0.25 mmol) and
Mn(OAc)3·2H2O (274 mg, 1.02 mmol) in AcOH (5 mL) was stirred
at r.t. for 30 min under an O2 atmosphere (1 atm). The mixture was
then diluted with EtOAc (100 mL), washed with sat. aq sodium bi-
sulfite (3 × 50 mL), sat. aq NaHCO3 (3 × 50 mL), and water (3 × 50
mL), dried (Na2SO4), and concentrated in vacuo. The crude product
was purified by column chromatography (silica gel, 20 g, EtOAc–
hexane, 1:3) followed by crystallization (CHCl3–hexane) to give 4a
(62 mg, 78%).
Anal. Calcd for C22H22N2O2: C, 76.28; H, 6.40; N, 8.09. Found: C,
76.33; H, 6.40; N, 7.98.
Method B: A mixture of 3a (103 mg, 0.25 mmol), Mn(OAc)2·4H2O
(18 mg, 0.07 mmol), and Co(OAc)2·4H2O (93 mg, 0.37 mmol) in
AcOH (5 mL) was heated at 80 °C for 5 min under an O2 atmo-
sphere (1 atm). The mixture was then diluted with EtOAc (100 mL),
washed with sat. aq sodium bisulfite (3 × 50 mL), sat. aq NaHCO3
(3 × 50 mL), and water (3 × 50 mL), dried (Na2SO4), and concen-
trated in vacuo. The crude product was purified by column chroma-
tography (silica gel, 20 g, EtOAc–hexane, 1:3) followed by
crystallization (CHCl3–hexane) to give 4a (67 mg, 84%).
6,7-Dimethyl-3-(morpholinocarbonyl)-2-phenylquinoline (4d)
Colorless crystals; yield: 67 mg (77%) (method A), 70 mg (86%)
(method B); mp 141–142 °C.
IR (KBr): 2860, 1625, 1440, 1110, 695 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.43–2.54 (m, 1 H, CH), 2.47 (s,
3 H, CH3), 2.50 (s, 3 H, CH3), 2.70 (ddd, J = 13.3, 5.1, 3.2 Hz, 1 H,
CH), 2.94 (ddd, J = 13.3, 8.0, 3.2 Hz, 1 H, CH), 3.24 (ddd, J = 11.5,
5.1, 3.2 Hz, 1 H, CH), 3.32 (ddd, J = 11.5, 8.0, 3.2 Hz, 1 H, CH),
3.51 (ddd, J = 13.3, 8.0, 3.2 Hz, 1 H, CH), 3.62 (ddd, J = 11.5, 5.1,
3.2 Hz, 1 H, CH), 3.78 (ddd, J = 13.3, 5.1, 3.2 Hz, 1 H, CH), 7.44–
7.53 (m, 3 H, HAr), 7.60 (s, 1 H, HAr), 7.82–7.87 (m, 2 H, HAr), 7.95
(s, 1 H, HAr), 8.15 (s, 1 H, HAr).
13C NMR (100.6 MHz, CDCl3): δ = 20.1 (q), 20.6 (q), 42.0 (t), 46.9
(t), 65.8 (t), 66.0 (t), 125.0 (s), 126.8 (d), 128.0 (s), 128.6 (2 d),
128.9 (d), 129.1 (2 d), 129.3 (d), 135.5 (d), 137.5 (s), 139.5 (s),
141.4 (s), 147.4 (s), 154.1 (s), 169.0 (s).
Colorless crystals; mp 149–150 °C.
IR (KBr): 2860, 1635, 1440, 1110, 775 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.51 (ddd, J = 11.4, 8.0, 3.2 Hz, 1
H, CH), 2.71 (ddd, J = 13.3, 5.1, 3.2 Hz, 1 H, CH), 2.96 (ddd,
J = 13.3, 8.0, 3.2 Hz, 1 H, CH), 3.26 (ddd, J = 11.4, 5.1, 3.2 Hz, 1
H, CH), 3.33 (ddd, J = 11.4, 8.0, 3.2 Hz, 1 H, CH), 3.53 (ddd,
J = 13.3, 8.0, 3.2 Hz, 1 H, CH), 3.64 (ddd, J = 11.4, 5.1, 3.2 Hz, 1
H, CH), 3.78 (ddd, J = 13.3, 5.1, 3.2 Hz, 1 H, CH), 7.46–7.55 (m, 3
H, HAr), 7.60 (t, J = 7.7 Hz, 1 H, HAr), 7.79 (t, J = 7.7 Hz, 1 H, HAr),
7.84–7.91 (m, 3 H, HAr), 8.19 (d, J = 8.5 Hz, 1 H, HAr), 8.28 (s, 1 H,
HAr).
Anal. Calcd for C22H22N2O2: C, 76.28; H, 6.40; N, 8.09. Found: C,
76.34; H, 6.41; N, 8.05.
13C NMR (100.6 MHz, CDCl3): δ = 42.0 (t), 46.8 (t), 65.6 (t), 65.9
(t), 126.3 (s), 127.2 (d), 127.6 (d), 128.6 (2 d), 128.8 (s), 129.0 (2 d),
129.5 (2 d), 130.7 (d), 136.5 (d), 139.2 (s), 148.1 (s), 155.0 (s),
168.5 (s).
6-Chloro-3-(morpholinocarbonyl)-2-phenylquinoline (4e)
Colorless crystals; yield: 97 mg (81%) (method A), 70 mg (86%)
(method B); mp 166–167 °C.
IR (KBr): 2860, 1620, 1460, 1115, 940 cm–1.
Anal. Calcd for C20H18N2O2: C, 75.45; H, 5.70; N, 8.80. Found: C,
75.38; H, 5.74; N, 8.75.
1H NMR (400 MHz, CDCl3): δ = 2.50 (ddd, J = 11.4, 8.0, 3.2 Hz, 1
H, CH), 2.69 (ddd, J = 13.3, 5.0, 3.2 Hz, 1 H, CH), 2.95 (ddd,
J = 13.3, 8.0, 3.2 Hz, 1 H, CH), 3.26 (ddd, J = 11.4, 5.0, 3.2 Hz, 1
H, CH), 3.33 (ddd, J = 11.4, 8.0, 3.2 Hz, 1 H, CH), 3.53 (ddd,
J = 13.3, 8.0, 3.2 Hz, 1 H, CH), 3.65 (ddd, J = 11.4, 5.0, 3.2 Hz, 1
H, CH), 3.78 (ddd, J = 13.3, 5.0, 3.2 Hz, 1 H, CH), 7.47–7.56 (m, 3
H, HAr), 7.72 (dd, J = 9.0, 2.4 Hz, 1 H, HAr), 7.82–7.89 (m, 3 H,
HAr), 8.12 (d, J = 9.0 Hz, 1 H, HAr), 8.19 (s, 1 H, HAr).
13C NMR (100.6 MHz, CDCl3): δ = 42.0 (t), 46.8 (t), 65.6 (t), 65.9
(t), 126.2 (d), 126.9 (s), 128.7 (2 d), 129.0 (2 d), 129.70 (d), 129.75
(s), 131.1 (d), 131.7 (d), 133.0 (s), 135.5 (d), 138.8 (s), 146.4 (s),
155.2 (s), 168.1 (s).
6-Methyl-3-(morpholinocarbonyl)-2-phenylquinoline (4b)
Colorless needles; yield: 64 mg (80%) (method A), 73 mg (90%)
(method B); mp 138–139 °C.
IR (KBr): 2860, 1620, 1435, 1110, 700 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.49 (ddd, J = 11.4, 8.0, 3.2 Hz, 1
H, CH), 2.57 (s, 3 H, CH3), 2.71 (ddd, J = 13.3, 5.0, 3.2 Hz, 1 H,
CH), 2.95 (ddd, J = 13.3, 8.0, 3.2 Hz, 1 H, CH), 3.25 (ddd, J = 11.4,
5.0, 3.2 Hz, 1 H, CH), 3.32 (ddd, J = 11.4, 8.0, 3.2 Hz, 1 H, CH),
3.52 (ddd, J = 13.3, 8.0, 3.2 Hz, 1 H, CH), 3.64 (ddd, J = 11.4, 5.0,
3.2 Hz, 1 H, CH), 3.79 (ddd, J = 13.3, 5.0, 3.2 Hz, 1 H, CH), 7.45–
7.54 (m, 3 H, HAr), 7.60–7.65 (m, 1 H, HAr), 7.63 (s, 1 H, HAr), 7.81–
7.89 (m, 2 H, HAr), 8.07 (d, J = 9.3 Hz, 1 H, HAr), 8.18 (s, 1 H, HAr).
Anal. Calcd for C20H17ClN2O2: C, 68.09; H, 4.86; N, 7.94. Found:
C, 67.96; H, 4.93; N, 7.87.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 175–182

180
P.-J. Tsai et al.
PAPER
(Phenyl)(2-phenylquinolin-3-yl)methanone (4f)
White needles; yield: 93 mg (80%) (method A), 66 mg (87%)
(method B); mp 133–134 °C.
3-Cyano-6-methyl-2-phenylquinoline (4j)
Colorless needles; yield: 61 mg (83%) (method A), 63 mg (85%)
(method B); mp 172–173 °C.
IR (KBr): 1655, 1595, 1270, 775, 690 cm–1.
IR (KBr): 2220, 1590, 1380, 830, 695 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.24–7.31 (m, 3 H, HAr), 7.33 (t,
J = 7.6 Hz, 2 H, HAr), 7.48 (t, J = 7.8 Hz, 1 H, HAr), 7.60–7.66 (m,
3 H, HAr), 7.72 (d, J = 7.6 Hz, 2 H, HAr), 7.84 (t, J = 7.8 Hz, 1 H,
HAr), 7.92 (d, J = 7.8 Hz, 1 H, HAr), 8.25 (d, J = 7.8 Hz, 1 H, HAr),
8.35 (s, 1 H, HAr).
13C NMR (100.6 MHz, CDCl3): δ = 125.8 (s), 127.3 (d), 128.1 (d),
128.4 (4 d), 128.8 (d), 129.3 (2 d), 129.7 (d), 130.0 (2 d), 131.2 (d),
132.8 (s), 133.3 (d), 137.0 (s), 137.6 (d), 139.7 (s), 148.3 (s), 157.5
(s), 196.9 (s).
1H NMR (400 MHz, CDCl3): δ = 2.59 (s, 3 H, CH3), 7.50–7.62 (m,
3 H, HAr), 7.66 (s, 1 H, HAr), 7.72 (dd, J = 8.6, 1.9 Hz, 1 H, HAr),
7.96–8.03 (m, 2 H, HAr), 8.10 (d, J = 8.6 Hz, 1 H, HAr), 8.57 (s, 1 H,
HAr).
13C NMR (100.6 MHz, CDCl3): δ = 21.6 (q), 105.4 (s), 118.1 (s),
125.0 (s), 126.4 (d), 128.6 (2 d), 129.0 (2 d), 129.5 (d), 129.9 (d),
135.3 (d), 137.7 (s), 138.3 (s), 143.4 (d), 147.3 (s), 157.1 (s).
Anal. Calcd for C17H12N2: C, 83.58; H, 4.95; N, 11.47. Found: C,
83.58; H, 4.97; N, 11.47.
Anal. Calcd for C22H15NO: C, 85.41; H, 4.89; N, 4.53. Found: C,
85.21; H, 5.01; N, 4.60.
6-Chloro-3-cyano-2-phenylquinoline (4k)
White needles; yield: 60 mg (82%) (method A), 70 mg (92%)
(method B); mp 197–198 °C.
IR (KBr): 2220, 1550, 1475, 925, 695 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.53–7.61 (m, 3 H, HAr), 7.82 (dd,
J = 9.0, 2.2 Hz, 1 H, HAr), 7.90 (d, J = 2.2 Hz, 1 H, HAr), 7.96–8.03
(m, 2 H, HAr), 8.15 (d, J = 9.0 Hz, 1 H, HAr), 8.58 (s, 1 H, HAr).
13C NMR (100.6 MHz, CDCl3): δ = 106.6 (s), 117.5 (s), 125.5 (s),
126.2 (d), 128.8 (2 d), 129.1 (2 d), 130.3 (d), 131.5 (d), 133.9 (d),
134.1 (s), 137.3 (s), 143.1 (d), 147.1 (s), 158.2 (s).
(6-Methyl-2-phenylquinolin-3-yl)(phenyl)methanone (4g)
White needles; yield: 88 mg (75%) (method A), 68 mg (86%)
(method B); mp 148–149 °C.
IR (KBr): 1660, 1445, 1270, 890, 735 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.58 (s, 3 H, CH3), 7.22–7.30 (m,
3 H, HAr), 7.32 (t, J = 7.6 Hz, 2 H, HAr), 7.47 (t, J = 7.6 Hz, 1 H,
HAr), 7.58–7.63 (m, 2 H, HAr), 7.65–7.69 (m, 2 H, HAr), 7.71 (d,
J = 8.2 Hz, 2 H, HAr), 8.14 (d, J = 9.2 Hz, 1 H, HAr), 8.25 (s, 1 H,
HAr).
13C NMR (100.6 MHz, CDCl3): δ = 21.6 (q), 125.8 (s), 126.8 (d),
128.3 (4 d), 128.6 (d), 129.2 (2 d), 129.3 (d), 129.9 (2 d), 132.7 (s),
133.2 (d), 133.5 (d), 136.9 (d), 137.1 (s), 137.3 (s), 139.8 (s), 147.0
(s), 156.5 (s), 197.1 (s).
Anal. Calcd for C16H9ClN2: C, 72.60; H, 3.43; N, 10.58. Found: C,
72.36; H, 3.46; N, 10.53.
(2-Methylquinolin-3-yl)(phenyl)methanone (4l)
Pale yellow oil; yield: 47 mg (64%) (method A).
IR (KBr): 1660, 1595, 1240, 880, 690 cm–1.
Anal. Calcd for C23H17NO: C, 85.42; H, 5.30; N, 4.33. Found: C,
85.27; H, 5.33; N, 4.29.
1H NMR (400 MHz, CDCl3): δ = 2.75 (s, 3 H, CH3), 7.51 (t, J = 7.6
Hz, 2 H, HAr), 7.56 (t, J = 7.8 Hz, 1 H, HAr), 7.65 (t, J = 7.6 Hz, 1 H,
HAr), 7.76–7.83 (m, 1 H, HAr), 7.80 (d, J = 7.8 Hz, 1 H, HAr), 7.85
(d, J = 7.6 Hz, 2 H, HAr), 8.09 (d, J = 7.8 Hz, 1 H, HAr), 8.13 (s, 1 H,
HAr).
13C NMR (100.6 MHz, CDCl3): δ = 24.2 (q), 125.3 (s), 126.6 (d),
128.1 (d), 128.7 (3 d), 130.1 (2 d), 131.0 (d), 132.2 (s), 133.7 (d),
136.7 (d), 137.3 (s), 148.0 (s), 156.6 (s), 196.7 (s).
(6-Chloro-2-phenylquinolin-3-yl)(phenyl)methanone (4h)
White needles; yield: 64 mg (78%) (method A), 68 mg (85%)
(method B); mp 161–162 °C.
IR (KBr): 1665, 1475, 1270, 885, 720 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.25–7.31 (m, 3 H, HAr), 7.34 (t,
J = 7.5 Hz, 2 H, HAr), 7.49 (t, J = 7.5 Hz, 1 H, HAr), 7.58–7.64 (m,
2 H, HAr), 7.70 (d, J = 7.5 Hz, 2 H, HAr), 7.76 (dd, J = 9.0, 2.3 Hz,
1 H, HAr), 7.89 (d, J = 2.3 Hz, 1 H, HAr), 8.18 (d, J = 9.0 Hz, 1 H,
HAr), 8.24 (s, 1 H, HAr).
HMRS (EI): m/z [M]+ calcd for C17H13NO: 247.0997; found:
247.0992.
13C NMR (100.6 MHz, CDCl3): δ = 126.4 (s), 126.6 (d), 128.4 (4 d),
129.0 (d), 129.2 (2 d), 129.9 (2 d), 131.2 (d), 132.1 (d), 133.0 (s),
133.5 (d), 133.6 (s), 136.5 (d), 136.7 (s), 139.3 (s), 146.7 (s), 157.6
(s), 196.5 (s).
(2,6-Dimethylquinolin-3-yl)(phenyl)methanone (4m)
Colorless needles; yield: 84 mg (75%) (method A); mp 68–69 °C.
IR (KBr): 1660, 1595, 1245, 830, 730 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.54 (s, 3 H, CH3), 2.72 (s, 3 H,
CH3), 7.50 (t, J = 7.7 Hz, 2 H, HAr), 7.56 (s, 1 H, HAr), 7.62 (dd,
J = 8.7, 1.9 Hz, 1 H, HAr), 7.64 (t, J = 7.7 Hz, 1 H, HAr), 7.84 (d,
J = 7.7 Hz, 2 H, HAr), 7.98 (d, J = 8.7 Hz, 1 H, HAr), 8.04 (s, 1 H,
HAr).
13C NMR (100.6 MHz, CDCl3): δ = 21.5 (q), 24.1 (q), 125.3 (s),
126.9 (d), 128.3 (d), 128.7 (2 d), 130.1 (2 d), 132.1 (s), 133.3 (d),
133.6 (d), 136.2 (d), 136.6 (s), 137.4 (s), 146.7 (s), 155.6 (s), 196.9
(s).
Anal. Calcd for C22H14ClNO: C, 76.86; H, 4.10; N, 4.07. Found: C,
76.77; H, 4.15; N, 4.03.
3-Cyano-2-phenylquinoline (4i)
White needles; yield: 57 mg (78%) (method A), 63 mg (87%)
(method B); mp 195–196 °C.
IR (KBr): 2220, 1555, 1375, 755, 690 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.52–7.61 (m, 3 H, HAr), 7.67 (t,
J = 7.9 Hz, 1 H, HAr), 7.90 (t, J = 7.9 Hz, 1 H, HAr), 7.91 (d, J = 7.9
Hz, 1 H, HAr), 7.97–8.04 (m, 2 H, HAr), 8.21 (d, J = 7.9 Hz, 1 H,
HAr), 8.67 (s, 1 H, HAr).
Anal. Calcd for C18H15NO: C, 82.73; H, 5.79; N, 5.36. Found: C,
82.59; H, 5.79; N, 5.32.
13C NMR (100.6 MHz, CDCl3): δ = 105.6 (s), 117.9 (s), 125.0 (s),
127.7 (d), 128.1 (d), 128.7 (2 d), 129.1 (2 d), 129.9 (d), 130.1 (d),
133.0 (d), 137.6 (s), 144.2 (d), 148.7 (s), 158.0 (s).
(6-Chloro-2-methylquinolin-3-yl)(phenyl)methanone (4n)
Colorless needles; yield: 64 mg (57%) (method A); mp 121–122 °C.
IR (KBr): 1660, 1595, 1275, 835, 725 cm–1.
Anal. Calcd for C16H10N2: C, 83.46; H, 4.38; N, 12.17. Found: C,
83.38; H, 4.38; N, 12.16.
1H NMR (400 MHz, CDCl3): δ = 2.72 (s, 3 H, CH3), 7.51 (t, J = 7.7
Hz, 2 H, HAr), 7.65 (t, J = 7.7 Hz, 1 H, HAr), 7.71 (dd, J = 8.9, 2.3
Hz, 1 H, HAr), 7.78 (d, J = 2.3 Hz, 1 H, HAr), 7.83 (d, J = 7.7 Hz, 2
H, HAr), 8.02 (d, J = 8.9 Hz, 1 H, HAr), 8.02 (s, 1 H, HAr).
Synthesis 2014, 46, 175–182
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Oxidative Radical Cyclizations of N-(2-Alkenylaryl)-Substituted Enamines
181
13C NMR (100.6 MHz, CDCl3): δ = 24.2 (q), 125.9 (s), 126.6 (d),
128.8 (2 d), 130.1 (2 d), 130.3 (d), 131.8 (d), 132.3 (s), 133.1 (s),
133.9 (d), 135.4 (d), 136.9 (s), 146.4 (s), 156.9 (s), 196.3 (s).
Anal. Calcd for C19H13NO2: C, 79.43; H, 4.56; N, 4.88. Found: C,
79.19; H, 4.53; N, 4.63.
3-Chlorobenzo[b]acridine-6,11-dione (12d)
Pale yellow needles; yield: 102 mg (90%) (method A), 85 mg (75%)
(method B); mp 332–333 °C.
Anal. Calcd for C17H12ClNO: C, 72.47; H, 4.29; N, 4.97. Found: C,
72.34; H, 4.35; N, 4.95.
IR (KBr): 1690, 1665, 1580, 1280, 980 cm–1.
Benzo[b]acridine-6,11-dione (12a); Typical Procedure
Method A: A mixture of 11a (107 mg, 0.30 mmol) and Mn(OAc)3·2
H2O (381 mg, 1.42 mmol) in HCO2H (7 mL) was heated at r.t. for
30 min under an O2 atmosphere (1 atm). The mixture was then di-
luted with EtOAc (100 mL), washed with sat. aq sodium bisulfite
(3 × 50 mL), sat. aq NaHCO3 (3 × 50 mL), and water (3 × 50 mL),
dried (Na2SO4), and concentrated in vacuo. The crude product was
purified by column chromatography (silica gel, 20 g, CH2Cl2–hex-
ane, 1:1) followed by crystallization (CHCl3–hexane) to give 12a
(64 mg, 86%).
1H NMR (400 MHz, CDCl3): δ = 7.87–7.93 (m, 3 H, HAr), 8.10 (d,
J = 2.2 Hz, 1 H, HAr), 8.39–8.43 (m, 1 H, HAr), 8.45 (d, J = 9.1 Hz,
1 H, HAr), 8.48–8.53 (m, 1 H, HAr), 9.14 (s, 1 H, HAr).
13C NMR (100.6 MHz, CDCl3): δ = 127.6 (d), 127.97 (d), 128.01
(s), 128.4 (d), 129.6 (s), 133.1 (d), 133.5 (s), 134.3 (d), 134.4 (s),
134.9 (d), 135.0 (d), 136.1 (s), 137.0 (d), 147.9 (s), 148.6 (s), 181.4
(s), 182.1 (s).
Anal. Calcd for C17H8ClNO2: C, 69.52; H, 2.75; N, 4.77. Found: C,
69.37; H, 2.77; N, 4.74.
Method B: A mixture of 11a (150 mg, 0.43 mmol), Mn(OAc)2·4
H2O (34 mg, 0.13 mmol), and Co(OAc)2·4 H2O (160 mg, 0.64
mmol) in AcOH (8 mL) was stirred at 80 °C for 5.5 h under an O2
atmosphere (1 atm). The mixture was then diluted with EtOAc (100
mL), washed with sat. aq sodium bisulfite (3 × 50 mL), sat. aq
NaHCO3 (3 × 50 mL), and water (3 × 50 mL), dried (Na2SO4), and
concentrated in vacuo. The crude product was purified by column
chromatography (silica gel, 20 g, CH2Cl2–hexane, 1:1) followed by
crystallization (CHCl3–hexane) to give 12a (83 mg, 75%).
Acknowledgment
We are grateful to the National Science Council of ROC for finan-
cial support (Grant No. NSC-100-2113-M-006-009-MY2).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
m
tgioSrantnugIifoop
r
itmnatr
Pale yellow needles; mp 310–311 °C.
IR (KBr): 1690, 1670, 1580, 1275, 975 cm–1.
1H NMR (400 MHz, CDCl3): δ = 7.78 (t, J = 8.0 Hz, 1 H, HAr),
7.86–7.92 (m, 2 H, HAr), 7.97 (td, J = 8.0, 1.3 Hz, 1 H, HAr), 8.12 (d,
J = 8.0 Hz, 1 H, HAr), 8.39–8.44 (m, 1 H, HAr), 8.48–8.54 (m, 1 H,
HAr), 8.51 (d, J = 8.0 Hz, 1 H, HAr), 9.23 (s, 1 H, HAr).
13C NMR (100.6 MHz, CDCl3): δ = 127.4 (s), 127.5 (d), 128.3 (d),
129.0 (s), 129.6 (d), 129.8 (d), 131.6 (d), 133.2 (d), 133.6 (s), 134.5
(s), 134.69 (d), 134.74 (d), 138.0 (d), 147.8 (s), 150.2 (s), 181.7 (s),
182.4 (s).
References
(1) (a) Neumann, W. P. Synthesis 1987, 665. (b) Curran, D. P.
Synthesis 1988, 417. (c) Curran, D. P. Synthesis 1988, 489.
(d) Giese, B.; Kopping, B.; Gobel, T.; Dickhaut, J.; Thoma,
G.; Kulicke, K. J.; Trach, F. In Organic Reactions; Vol. 48;
John Wiley: New York, 1996, Chap. 2, 301–855.
(e) Bowman, W. R.; Bridge, C. F.; Brookes, P. J. Chem.
Soc., Perkin Trans. 1 2000, 1. (f) Zheng, W. Tetrahedron
2001, 57, 7237. (g) Rowlands, G. J. Tetrahedron 2009, 65,
8603. (h) Rowlands, G. J. Tetrahedron 2010, 66, 1593.
(2) (a) Melikyan, G. G. Synthesis 1993, 833. (b) Iqbal, J.;
Bhatia, B.; Nayyar, N. K. Chem. Rev. 1994, 94, 519.
(c) Snider, B. B. Chem. Rev. 1996, 96, 339. (d) Nair, V.;
Panicker, S. B.; Nair, L. G.; George, T. G.; Augustine, A.
Synlett 2003, 156. (e) Nair, V.; Balagopal, L.; Rajan, R.;
Mathew, J. Acc. Chem. Res. 2004, 37, 21. (f) Pan, X.-Q.;
Zou, J.-P.; Zhang, W. Mol. Diversity 2009, 13, 421.
(3) (a) Oumar-Mahamat, H.; Moustrou, C.; Surzur, J.-M.;
Berstrand, M. P. J. Org. Chem. 1989, 54, 5684. (b) Snider,
B. B.; Wan, B. Y. F.; Buckman, B. O.; Foxman, B. M.
J. Org. Chem. 1991, 56, 328.
Anal. Calcd for C17H9NO2: C, 78.76; H, 3.50; N, 5.40. Found: C,
78.66; H, 3.42; N, 5.40.
3-Methylbenzo[b]acridine-6,11-dione (12b)
Pale yellow needles; yield: 91 mg (90%) (method A), 86 mg (78%)
(method B); mp 284–285 °C.
IR (KBr): 1695, 1665, 1575, 1275, 975 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.62 (s, 3 H, CH3), 7.77 (dd,
J = 8.7, 1.6 Hz, 1 H, HAr), 7.83–7.90 (m, 2 H, HAr), 7.84 (s, 1 H,
HAr), 8.37 (d, J = 8.7 Hz, 1 H, HAr), 8.37–8.41 (m, 1 H, HAr), 8.46–
8.51 (m, 1 H, HAr), 9.09 (s, 1 H, HAr).
13C NMR (100.6 MHz, CDCl3): δ = 21.8 (q), 127.4 (d s), 128.2 (2
d), 129.1 (s), 131.2 (d), 133.6 (s), 134.4 (s), 134.5 (d), 134.6 (d),
135.7 (d), 136.9 (d), 140.4 (s), 147.1 (s), 148.8 (s), 181.7 (s), 182.5
(s).
(4) (a) Citterio, A.; Sebastiano, R.; Marion, A. J. Org. Chem.
1991, 56, 5328. (b) Citterio, A.; Sebastiano, R.; Nicolini, M.
Tetrahedron 1993, 49, 7743. (c) Wu, Y.-L.; Chuang, C.-P.;
Lin, P.-Y. Tetrahedron 2000, 56, 6209. (d) Liao, Y.-J.; Wu,
Y.-L.; Chuang, C.-P. Tetrahedron 2003, 59, 3511.
Anal. Calcd for C18H11NO2: C, 79.11; H, 4.06; N, 5.13. Found: C,
78.90; H, 4.12; N, 5.07.
(5) (a) Jiang, M.-C.; Chuang, C.-P. J. Org. Chem. 2000, 65,
5409. (b) Wu, Y.-L.; Chuang, C.-P.; Lin, P.-Y. Tetrahedron
2001, 57, 5543. (c) Tsai, A.-I.; Wu, Y.-L.; Chuang, C.-P.
Tetrahedron 2001, 57, 7829. (d) Tseng, C.-C.; Wu, Y.-L.;
Chuang, C.-P. Tetrahedron 2002, 58, 7625. (e) Tseng, C.-
M.; Wu, Y.-L.; Chuang, C.-P. Tetrahedron 2004, 60, 12249.
(f) Chen, H.-L.; Lin, C.-Y.; Cheng, Y.-C.; Tsai, A.-I.;
Chuang, C.-P. Synthesis 2005, 977. (g) Lin, C.-Y.; Cheng,
Y.-C.; Tsai, A.-I.; Chuang, C.-P. Org. Biomol. Chem. 2006,
4, 1097.
1,3-Dimethylbenzo[b]acridine-6,11-dione (12c)
Pale yellow needles; yield: 104 mg (91%) (method A), 82 mg (76%)
(method B); mp 285–286 °C.
IR (KBr): 1685, 1665, 1575, 1275, 975 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.56 (s, 3 H, CH3), 2.95 (s, 3 H,
CH3), 7.62 (s, 1 H, HAr), 7.67 (s, 1 H, HAr), 7.82–7.89 (m, 2 H, HAr),
8.36–8.42 (m, 1 H, HAr), 8.45–8.49 (m, 1 H, HAr), 9.03 (s, 1 H, HAr).
13C NMR (100.6 MHz, CDCl3): δ = 18.0 (q), 21.9 (q), 126.2 (d),
127.3 (s), 127.4 (d), 128.1 (d), 129.3 (s), 133.7 (s), 134.4 (d), 134.6
(d), 134.7 (s), 135.8 (d), 137.0 (d), 139.6 (s), 140.2 (s), 146.1 (s),
148.1 (s), 181.8 (s), 182.9 (s).
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Synthesis 2014, 46, 175–182
© Georg Thieme Verlag Stuttgart · New York