Manganese(III) acetate mediated oxidative radical cyclizations of α-substituted N-[(E)-stilben-2-yl]acetamides

Article abstract of DOI:10.1016/j.tet.2015.05.043

A synthetic method of 3-substituted 2-quinolinones from readily available α-substituted N-[(E)-stilben-2-yl]acetamides have been developed. α-Carbonylalkyl radical, produced by the manganese(III) acetate oxidation of N-[(E)-stilben-2-yl]acetamides, undergoes an intramolecular 6-exo-dig cyclization onto the CC bond efficiently and 2-quinolinones was produced. A variety of functional groups, including benzoyl, acetyl, cyano, and ethoxycarbonyl groups, are compatible with the reaction conditions. Under Mn(II)/Co(II)/O₂ conditions, these N-[(E)-stilben-2-yl]acetamides were also converted into the corresponding 2-quinolinones effectively and a catalytic amount of manganese(II) acetate was used.

Full text of DOI:10.1016/j.tet.2015.05.043

Tetrahedron 71 (2015) 4795e4800
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Manganese(III) acetate mediated oxidative radical cyclizations of
a-substituted N-[(E)-stilben-2-yl]acetamides
*
Ghien-An Lin, Che-Ping Chuang
Department of Chemistry, National Cheng Kung University, Tainan 70101, Taiwan, ROC
a r t i c l e i n f o
a b s t r a c t
Article history:
A synthetic method of 3-substituted 2-quinolinones from readily available a-substituted N-[(E)-stilben-
Received 23 January 2015
Received in revised form 9 May 2015
Accepted 12 May 2015
2-yl]acetamides have been developed. a-Carbonylalkyl radical, produced by the manganese(III) acetate
oxidation of N-[(E)-stilben-2-yl]acetamides, undergoes an intramolecular 6-exo-dig cyclization onto the
C]C bond efficiently and 2-quinolinones was produced. A variety of functional groups, including ben-
zoyl, acetyl, cyano, and ethoxycarbonyl groups, are compatible with the reaction conditions. Under
Mn(II)/Co(II)/O2 conditions, these N-[(E)-stilben-2-yl]acetamides were also converted into the corre-
sponding 2-quinolinones effectively and a catalytic amount of manganese(II) acetate was used.
Ó 2015 Elsevier Ltd. All rights reserved.
Available online 4 June 2015
Keywords:
Manganese(III) acetate
Oxidative
Free radical
N-[(E)-stilben-2-yl]acetamides
Quinolinones
1. Introduction
employed in the synthesis of 2-quinolinones including radical cy-
clization of anilides,8 cyclization of Baylis-Hillman adducts,9 Pd-
The addition of carbon-centered radicals to alkenes is an effec-
tive tool for the formation of carbonecarbon bonds, and many new
methods proceeding through radical reactions have been de-
veloped for the synthesis of useful and structure diverse organic
molecules.1,2 Metal salts [Mn(III), Ce(IV), and Ag(I)] can readily
catalyzed cyclocarbonylation of 2-alkenylanilines,10 Pd-catalyzed
amidation of 3-arylacrylamides,11 Ru-catalyzed oxidative cycliza-
tion of 2-(3-hydroxypropyl)aniline,12 and Ru-mediated addition-
cyclization between aminophenylboronates and enones.13 Al-
though a number of methods are available as cited above, the
search for newer methods for 2-quinolinone synthesis is continu-
ously being pursued. As part of our study on the development of
new routes to heterocyclic systems,14e17 we now report a man-
ganese(III) mediated synthesis of 3-substituted 2-quinolinones
undergo a ligand-exchange reaction with
to produce metal-enolate complex, which then undergoes one-
electron oxidation to produce a-dicarbonylalkyl radical. This
a-dicarbonyl compound
a
-
dicarbonylalkyl radical can undergo efficient oxidative addition to
the C]C bond. The metal salts mediated oxidative radical reactions
have been explored extensively, and they have become valuable
methods for the formation of highly functionalized compounds.2e5
Among them, the oxidative intramolecular cyclization reaction is
one of the efficient methods for the synthesis of cyclic compounds.
Quinolinones have attracted considerable attention for their
known biological activities and pharmacological properties, which
include antiviral (HIV) activities,6aec inotropic,6d 5HT3 receptor
antagonists,6e farnesyl transferase inhibitors,6f and maxi-K channel
opening agents.6g Thus, considerable efforts have been made to-
ward the development of efficient methods for their syntheses. In
addition to classic base-catalyzed Friedlӓnder reaction and acid-
catalyzed Knorr reaction,7 several alternative methods have been
from a-substituted N-[(E)-stilben-2-yl]acetamides.
2. Results and discussion
Our studies commenced with the readily available 2-
ethoxycarbonyl-N-[(E)-stilben-2-yl]acetamide 1aa (R1]CO2Et,
R2]H, R3]H, R4]TMBn), which was prepared by the acylation of
(E)-stilben-2-ylamine with ethyl malonyl chloride (see
Supplementary data). With this acetamide 1aa in hand, we first
examined the radical reaction of 1aa with manganese(III) acetate
under various reaction conditions (Table 1). The reaction of 1aa and
manganese(III) acetate (4 equiv) was carried out in DCE at 70 ꢀC
under a nitrogen atmosphere until 1aa was completely consumed
(7 h). The cyclization product 2a was produced exclusively in 61%
yield and the expected 4-benzyl substituted 2-quinolinone 3aa,
derived from the Mn(III) mediated oxidative elimination of radical
intermediate 7aa followed by double bond migration, was not
* Corresponding author. Fax: þ886 6 2740552; e-mail address: cpchuang@mail.
ncku.edu.tw (C.-P. Chuang).
http://dx.doi.org/10.1016/j.tet.2015.05.043
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

4796
G.-A. Lin, C.-P. Chuang / Tetrahedron 71 (2015) 4795e4800
Table 1
Optimization of reaction conditions with 2-ethoxycarbonyl-N-[(E)-stilben-2-yl]
acetamide 1aa18a
Solvent
Temp
t (h)
Product (Yield (%))a
1
2
3
4
5
6
7
8
9c
DCE
DCE
DCE
HOAc
CH3CN
C6H6
DME
1,4-dioxane
DCE
N2
Air
O2
O2
O2
O2
O2
O2
Air
70 ꢀC
70 ꢀC
70 ꢀC
70 ꢀC
70 ꢀC
70 ꢀC
70 ꢀC
70 ꢀC
70 ꢀC
7
7
7
1
7
2a (61)
2a (84)
2a (86)
2a (74)
2a (77)
2a (79)
2a (76)
2a (67)b
2a (nd)
7
24
24
7
a
Yield of isolated product.
Based on 85% conversion of starting 1aa.
TEMPO (2 equiv) was added. DCE¼1,2-dichloroethane. DME¼1,2-dimeth
b
c
oxyethane. TEMPO¼2,2,6,6-tetramethylpiperidinyloxy.
observed (Table 1, entry 1). It is noteworthy that the yield can be
improved to 84% under air instead of a nitrogen atmosphere (entry
2). Under an oxygen atmosphere, 2-quinolinone 2a was formed in
a slightly higher yield (entry 3). In attempt to investigate the range
of solvents compatible with this reaction, reaction between 1aa and
manganese(III) acetate was next performed in other solvents. In
acetic acid, it proceeded much faster (1 h), however, a lower yield
(74%) of 2a was obtained (entry 4). In acetonitrile and benzene, it
required 7 h at 70 ꢀC to go to completion and 2a was produced in
77% and 79% yields, respectively (entries 5 and 6). In DME and 1,4-
dioxane, the desired product 2a was produced in lower yields
(entries 7 and 8).
Scheme 1.
To gain insight into the possible reaction mechanism, the re-
action of 1aa with manganese(III) acetate was then carried out in
the presence of TEMPO (2 equiv), an effective radical scavenger
(entry 9). No trace of 2a was detected, indicating that this reaction
presumably involves a radical process. Since dioxygen plays an
important role in this reaction, a possible mechanism for the for-
mation of 2-quinolinone 2a is outlined in Scheme 1. Initiation oc-
curs with the chelation of manganese(III) acetate by the enolate
oxygen of 1aa to produce Mn(III)-complex 5aa. Subsequently, ho-
molytic cleavage of Mn(III)-complex 5aa takes place to generate
radical 6aa and manganese(II) acetate. This resulting radical in-
termediate 6aa undergoes a 6-exo-trig cyclization to give radical
7aa, which is then trapped by O2 to give peroxy radical in-
termediate 8aa. Finally, hydroperoxide 9aa, formed by the intra-
molecular hydrogen atom abstraction of 8aa, undergoes
fragmentation to produce 2-quinolinone 2a and benzaldehyde.18a
With these optimized reaction conditions in hand (Table 1, entry
2, Method A), we next explored the scope and limitations of this
process, and the results are summarized in Table 2. In all cases, N-
[(E)-stilben-2-yl]acetamides 1 were converted to the correspond-
ing 2-quinolinones 2 effectively. By varying substituents R1 of
acetamides 1, it was shown that several useful functional groups,
including ethoxycarbonyl, acetyl, cyano, and benzoyl groups, were
tolerated toward the reaction conditions. Substrates bearing dif-
ferent functional groups (R2) on the aniline moiety, including 4-
chloro, 4-fluoro, 4-methoxylcarbonyl, 4-methyl, and 4,5-dimethyl,
regardless if they were electronic-withdrawing or -donating, all
worked well in moderate to good yields (entries 1e6). However,
with 1ga (R2¼4,6-dimethyl) bearing a methyl group on the 6-
position of aniline fragment, it proceeded much slower (24 h)
and 2g was obtained in slightly lower yield (entry 7). This is pre-
sumably due to the steric effect between 6-Me and N-TMBn groups.
Indeed, by decreasing the size of R4 group, the reaction time for 1ha
(R4]Bn) was shorten to 5 h and 2h was afforded in 76% yield (entry
8). With unprotected amides 1iaeka (R4]H), the desired oxidative
cyclization products 2iek were also obtained in acceptable yields
(entries 9e11). A variety of aryl substituents (R3) at the terminal of
C]C, such as methyl, methoxy, chloro, and cyano groups, was well
tolerated under the reaction conditions and 2a was obtained in
comparable yields (entries 12e15). This manganese(III) acetate
mediated oxidative radical reaction of N-[(E)-stilben-2-yl]acet-
amides 1 provides a straightforward method for the synthesis of 3-
substituted 2-quinolinones 2. The traditional harshly basic and
acidic conditions can be avoided.
A
a-carbonylalkyl radical, produced by the Mn(II)/Co(II)/O2
conditions, undergoes efficient addition to the C]C bond.19 In this
reaction, Mn(III) can be regenerated from Mn(II) by the oxidation of
Co(III)-dioxygen complex and a catalytic amount of Mn(II) is used.
Due to the much lower cost of manganese(II) acetate and cobalt(II)
acetate, we next examined the radical cyclization reaction of N-[(E)-
stilben-2-yl]acetamides 1 under the Mn(II)/Co(II)/O2 conditions to
develop greener reaction conditions.
When N-[(E)-stilben-2-yl]acetamide 1aa was reacted with
manganese(II) acetate (0.3 equiv) and cobalt(II) acetate (2 equiv) in
acetic acid at 80 ꢀC under an oxygen atmosphere, the target cycli-
zation product 2a was obtained in 68% yield (Table 3, entry 1). The
cobalt(II) acetate loading can be decreased to 0.5 equiv without
lowering the product yield (entry 2). Under air atmosphere, it
proceeded much slower (1.5 h) and 2-quinolinone 2a was formed in
61% yield (entry 3). Other acetamides 1 were also employed to
examine the scope of this oxidative radical reaction using the
Mn(II)/Co(II)/O2 conditions (Table 3, Method B). In all cases, N-[(E)-
stilben-2-yl]acetamides 1 were successfully converted to the cor-
responding 2-quinolinones 2.

G.-A. Lin, C.-P. Chuang / Tetrahedron 71 (2015) 4795e4800
4797
Table 2
Table 3
Reactions of N-[(E)-stilben-2-yl]acetamides
1
under Mn(III)/DCE conditions
Reactions of N-[(E)-stilben-2-yl]acetamides
1
under Mn(II)/Co(II) conditions
(Method A)a
(Method B)a,18a
R1
R2
R3
R4
t (h)
Product (Yield (%)b
R1
R2
R3
R4
TMBn
TMBn 10
TMBn 16
TMBn 16
TMBn
TMBn
TMBn 24
Bn
H
H
H
TMBn
t (h) Product (Yield (%)b
1
2
3
4
5
6
7
8
1aa
1aa
1aa
1ba
1ca
1ea
1fa
1ga
1oa
1pa
1qa
1ra
1sa
1ta
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CN
H
H
H
4-Cl
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
TMBn
TMBn
TMBn
TMBn
TMBn
TMBn
TMBn
TMBn
TMBn
TMBn
TMBn
TMBn
TMBn
TMBn
TMBn
TMBn
TMBn
0.5
0.5
1.5
0.5
0.5
0.5
0.5
0.5
9
2a (68)c
2a (69)
2a (61)d
2b (67)
2c (66)
2e (65)
2f (67)
2g (53)
2o (65)
2p (65)
2q (66)
2r (73)
2s (74)
2t (73)
2u (75)
2v (72)
2w (70)
1
2
3
4
5
6
7
8
9
1aa
1ba
1ca
1da
1ea
1fa
1ga
1ha
1ia
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
COMe
H
4-Cl
4- F
H
H
H
H
H
H
H
H
H
H
H
Me
7
2a (84)18a
2b (79)18a
2c (77)18a
2d (84)18a
2e (88)18a
2f (82)18a
2g (78)18a
2h (76)18a
2i (61)18a
2j (68)18a
2k (65)18a
2a (87)18a
2a (87)18b
2a (89)18a
2a (89)18c
2l (61)18a
2m (64)18a
2n (66)18a
2o (73)18a
2p (76)18a
2q (75)18a
2r (74)18a
2s (70)18a
2t (73)18a
2u (78)18a
2v (72)18a
2w (53)18a
4- CO2Me
4-Me
4,5-diMe
4,6-diMe
4.6-diMe
4-Cl
4-Me
4,5-diMe
H
H
H
H
H
4- F
7
9
4-Me
4,5-diMe
4,6-diMe
H
4-Me
4-Cl
H
4-Cl
4- F
5
9
7
7
5
9
5
7
9
10
11
12
13
14
15
16
17
CN
CN
11
9
10 1ja
11 1ka
12 1ab
13 1ac
14 1ad
15 1ae
16 1la
COPh
COPh
COPh
COPh
COPh
COPh
0.5
0.5
0.5
0.5
0.5
0.5
OMe TMBn
Cl
CN
H
H
H
H
H
H
H
H
H
H
H
H
TMBn
TMBn
TMBn
TMBn
TMBn
TMBn 13
TMBn 13
TMBn 16
TMBn
TMBn
TMBn
TMBn
TMBn
TMBn
1ua
1va
1wa
4-Me
4,5-diMe
4,6-diMe
1
1.5
1.5
17 1ma COMe 4-Me
18 1na
19 1oa
20 1pa
21 1qa
22 1ra
23 1sa
24 1ta
25 1ua
26 1va
27 1wa
COMe 4-Cl
CN
CN
CN
COPh
COPh
COPh
COPh
COPh
COPh
a
The reaction was carried out using 0.34 mmol of 1 with 0.10 mmol of Mn(OAc)2
H
4-Me
4-Cl
H
4-Cl
and 0.17 mmol of Co(OAc)2 in 5 mL of acetic acid at 80 ꢀC under O2 atmosphere.
b
Yield of isolated product.
Co(OAc)2 (2 equiv) was used.
The reaction was performed under air atmosphere. TMBn¼2,4,6-trimethyl
c
6
7
9
4
3
8
d
benzyl.
4- F
4-Me
4,5-diMe
4,6-diMe
JMS-SX 102A mass spectrometer. Analytical thin-layer chroma-
tography was performed 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 silica gel (70e230 mesh).
a
The reaction was carried out using 0.34 mmol of 1 with 1.36 mmol of Mn(OAc)3
in 5 mL of DCE at 70 ꢀ C under air atmosphere.
b
Yield of isolated product. DCE¼1,2-dichloroethane. TMBn¼2,4,6-trimethyl
benzyl.
3. Conclusion
4.1.1. Typical experimental procedure for the manganese(III) medi-
ated radical cyclization reactions (Method A). A mixture of 2-
ethoxycarbonyl-N-[(E)-stilben-2-yl]acetamides (1aa; 150 mg,
0.34 mmol) and manganese(III) acetate (366 mg, 1.36 mmol) in 1,2-
dichloroethane (5 mL) was stirred at 70 ꢀC for 7 h under an at-
mosphere of air. The reaction mixture was then diluted with ethyl
acetate (50 mL), washed with saturated aqueous sodium bisulfite
(3ꢁ50 mL), and water (3ꢁ50 mL), dried (Na2SO4), and concentrated
in vacuo. The crude product was purified by column chromatog-
raphy over silica gel (20 g) (eluted with 1:8 ethyl acetateehexane)
followed by crystallization (ethyl acetateehexane) to give 2a
(100 mg, 84%).
The syntheses of 3-substituted 2-quinolinones from
substituted N-[(E)-stilben-2-yl]acetamides are described. -Car-
a-
a
bonylalkyl radical can be produced by the manganese(III) acetate
oxidation of N-[(E)-stilben-2-yl]acetamides, and, which undergo an
intramolecular 6-exo-dig cyclization onto the C]C bond efficiently.
This reaction provides a synthetically useful method for the syn-
thesis of 3-substituted 2-quinolinones. Compared to the traditional
methods, this process has the advantages such as mild reaction
conditions, high reaction yields and tolerance of a broad range of
functional groups, including ethoxycarbonyl, acetyl, benzoyl, and
cyano groups. Under Mn(II)/Co(II)/O2 conditions, these N-[(E)-stil-
ben-2-yl]acetamides were also converted into the corresponding 2-
quinolinones effectively. In these conditions, a catalytic amount of
manganese(II) acetate was used.
4.1.2. Typical experimental procedure for the Mn(II)/Co(II) catalyzed
radical cyclization reactions (Method B). A mixture of 2-
ethoxycarbonyl-N-[(E)-stilben-2-yl]acetamide (1aa; 150 mg,
0.34 mmol), manganese(II) acetate (27 mg, 0.10 mmol), and
cobalt(II) acetate (42 mg, 0.17 mmol) in acetic acid (5 mL) was
stirred at 80 ꢀC for 0.5 h under an oxygen atmosphere (1 atm). The
reaction mixture was then diluted with ethyl acetate (50 mL),
washed with saturated aqueous sodium bisulfite (1ꢁ50 mL), and
water (3ꢁ50 mL), dried (Na2SO4), and concentrated in vacuo. The
crude product was purified by column chromatography over silica
gel (20 g) (eluted with 1:8 ethyl acetateehexane) followed by
crystallization (ethyl acetateehexane) to give 2a (82 mg, 69%).
4. Experimental section
4.1. General
Melting points are uncorrected. Infrared spectra were taken
with a Hitachi 260-30 spectrometer. 1H and 13C NMR spectra were
recorded on a Bruker AMX-400 spectrometer. Chemical shifts are
reported in ppm relative to TMS as internal reference. The multi-
plicity of the 13C NMR signals was determined by means of DEPT
135 experiments. Elemental analyses were performed with Her-
aeus CHN-Rapid Analyzer. Mass spectra were recorded on a Jeol
4.1.3. 3-Ethoxycarbonyl-1-(2,4,6-trimethylbenzyl)quinolin-2(1H)-
one 2a. Light yellow crystals; mp 127e128 ꢀC (ethyl

4798
G.-A. Lin, C.-P. Chuang / Tetrahedron 71 (2015) 4795e4800
acetateehexane); IR (KBr) 1745, 1650, 1565, 1450, 1210 cmꢂ1
NMR (400 MHz, CDCl3)
;
1H
acetateehexane); IR (KBr) 1695, 1660, 1560, 1460, 1240 cmꢂ1
NMR (400 MHz, CDCl3)
2.21 (s, 6H, 2ꢁ CH3), 2.22 (s, 3H, CH3), 2.24 (s, 3H, CH3), 4.42 (q,
J¼7.1 Hz, 2H, OCH2), 5.63 (s, 2H, NCH2), 6.79 (s, 2H, ArH), 6.83 (s, 1H,
ArH), 7.33 (s, 1H, ArH), 8.34 (s, 1H, CH); 13C NMR (100.6 MHz, CDCl3)
;
1H
d
1.43 (t, J¼7.1 Hz, 3H, CH3), 2.18 (s, 6H, 2ꢁ
d
1.42 (t, J¼7.1 Hz, 3H, CH3), 2.18 (s, 3H, CH3),
CH3), 2.22 (s, 3H, CH3), 4.44 (q, J¼7.1 Hz, 2H, OCH2), 5.67 (s, 2H,
NCH2), 6.79 (s, 2H, ArH), 7.00 (d, J¼8.7 Hz,1H, ArH), 7.16 (t, J¼7.5 Hz,
1H, ArH), 7.39 (ddd, J¼8.7, 7.5, 1.4 Hz, 1H, ArH), 7.61 (dd, J¼7.5,
1.4 Hz, 1H, ArH), 8.40 (s, 1H, CH); 13C NMR (100.6 MHz, CDCl3)
d
14.3
d
14.3 (q), 18.9 (q), 20.3 (2ꢁ q), 20.7 (q), 21.0 (q), 42.2 (t), 61.4 (t),
(q), 20.3 (2ꢁ q), 20.7 (q), 42.5 (t), 61.6 (t), 115.1 (d), 119.1 (s), 122.4
(d),122.5 (s),130.2 (2ꢁ d),130.3 (d), 132.6 (d), 135.9 (2ꢁ s),136.6 (s),
140.7 (s), 143.8 (d), 159.7 (s), 165.0 (s); Anal. Calcd for C22H23NO3: C,
75.62; H, 6.63; N, 4.01. Found: C, 75.59; H, 6.66; N, 4.01.
116.1 (d), 117.3 (s), 121.1 (s), 130.1 (2ꢁ d), 130.2 (d), 130.6 (s), 131.4
(s), 136.0 (2ꢁ s), 136.5 (s), 139.2 (s), 142.8 (s), 143.6 (d), 159.7 (s),
165.3 (s); Anal. Calcd for C24H27NO3: C, 76.36; H, 7.21; N, 3.70.
Found: C, 76.33; H, 7.18; N, 3.68.
4.1.4. 6-Chloro-3-ethoxycarbonyl-1-(2,4,6-trimethylbenzyl)quinolin-
4.1.9. 3-Ethoxycarbonyl-6,8-dimethyl-1-(2,4,6-trimethylbenzyl)qui-
2(1H)-one 2b. Light yellow needles; mp 171e172 ꢀC (ethyl aceta-
nolin-2(1H)-one 2g. Yellow oils; IR (Neat) 1740, 1660, 1570, 1280,
teehexane); IR (KBr) 1705, 1660, 1485, 1290, 1255 cmꢂ1
;
1H NMR
1235 cmꢂ1; 1H NMR (400 MHz, CD2Cl2)
2.03 (s, 6H, 2ꢁ CH3), 2.21 (s, 3H, CH3), 2.38 (s, 3H, CH3), 2.63 (s, 3H,
CH3), 4.26 (q, J¼7.1 Hz, 2H, OCH2), 5.30 (s, 2H, NCH2), 6.75 (s, 2H, ArH),
7.29 (s,1H, ArH), 7.30 (s,1H, ArH), 8.21 (s,1H, CH); 13C NMR (100.6 MHz,
d
1.32 (t, J¼7.1 Hz, 3H, CH3),
(400 MHz, CDCl3)
d
1.43 (t, J¼7.1 Hz, 3H, CH3), 2.17 (s, 6H, 2ꢁ CH3), 2.23
(s, 3H, CH3), 4.44 (q, J¼7.1 Hz, 2H, OCH2), 5.64 (s, 2H, NCH2), 6.79 (s, 2H,
ArH), 6.94 (d, J¼9.1 Hz, 1H, ArH), 7.33 (dd, J¼9.1, 2.5 Hz, 1H, ArH), 7.58
(d, J¼2.5 Hz, 1H, ArH), 8.29 (s, 1H, CH); 13C NMR (100.6 MHz, CDCl3)
CDCl3)
d
14.2 (q), 20.2 (q), 20.3 (2ꢁ q), 20.7 (q), 23.2 (q), 49.8 (t), 61.3 (t),
d
14.3 (q), 20.3 (2ꢁ q), 20.7 (q), 42.5 (t), 61.8 (t),116.6 (d),120.0 (s),123.8
121.1 (s), 122.5 (s), 124.7 (s), 128.6 (d), 129.7 (2ꢁ d), 130.9 (s), 132.2 (s),
136.2 (s),136.3 (2ꢁ s), 138.7 (d), 141.9 (s), 143.9 (d),160.6 (s), 164.7 (s);
HMRS (EI): calcd for C24H27NO3 377.1991; found 377.1984.
(s), 127.9 (s), 129.0 (d), 129.9 (s), 130.3 (2ꢁ d), 132.5 (d), 135.9 (2ꢁ s),
136.9 (s), 139.0 (s), 142.3 (d), 159.3 (s), 164.6 (s); Anal. Calcd for
C22H22ClNO3: C, 68.83; H 5.78; N, 3.65. Found: C, 68.90; H, 5.83; N, 3.64.
4.1.10. 1-Benzyl-3-ethoxycarbonyl-6,8-dimethylquinolin-2(1H)-one
4.1.5. 3-Ethoxycarbonyl-6-fluoro-1-(2,4,6-trimethylbenzyl)quinolin-
2(1H)-one 2c. Light yellow needles; mp 136e137 ꢀC (ethyl aceta-
2h. Light yellow needles; mp 101e102 ꢀC (ethyl acetateehexane);
IR (KBr) 1695, 1660, 1565, 1450, 1240 cmꢂ1 1H NMR (400 MHz,
;
teehexane); IR (KBr) 1700, 1655, 1570, 1255, 1235 cmꢂ1
;
1H NMR
CDCl3)
d
1.40 (t, J¼7.1 Hz, 3H, CH3), 2.35 (s, 3H, CH3), 2.53 (s, 3H, CH3),
(400 MHz, CDCl3)
d
1.43 (t, J¼7.1 Hz, 3H, CH3), 2.17 (s, 6H, 2ꢁ CH3),
4.41 (q, J¼7.1 Hz, 2H, OCH2), 5.71 (brs, 2H, NCH2), 7.05 (d, J¼7.3 Hz,
2.23 (s, 3H, CH3), 4.44 (q, J¼7.1 Hz, 2H, OCH2), 5.66 (s, 2H, NCH2), 6.80
(s, 2H, ArH), 6.97 (dd, J¼9.4, 4.3 Hz, 1H, ArH), 7.13 (ddd, J¼9.4, 8.0,
2H, ArH), 7.16e7.23 (m, 2H, ArH), 7.24e7.30 (m, 2H, ArH), 7.31 (s,1H,
ArH), 8.39 (s, 1H, CH); 13C NMR (100.6 MHz, CDCl3)
d 14.3 (q), 20.1
2.9 Hz,1H, ArH), 7.28 (dd, J¼8.0, 2.9 Hz,1H, ArH), 8.30 (s,1H, CH). 13
C
(q), 23.8 (q), 49.7 (t), 61.5 (t),121.0 (s),121.9 (s),124.4 (s),125.5 (2ꢁ d),
126.7 (d), 128.7 (2ꢁ d), 129.4 (d), 132.4 (s), 138.2 (s), 139.7 (d), 140.1
(s), 145.1 (d),160.6 (s), 165.1 (s); Anal. Calcd for C21H21NO3: C, 75.20;
H, 6.31; N, 4.18. Found: C, 75.26; H, 6.33; N, 4.15.
NMR (100.6 MHz, CDCl3)
d
14.3 (q), 20.3 (2ꢁ q), 20.7 (q), 42.6 (t), 61.7
(t), 114.7 (dd, JCeF¼22.1 Hz), 116.9 (dd, JCeF¼8.0 Hz), 119.8 (d,
JCeF¼9.1 Hz), 120.5 (dd, JCeF¼23.1 Hz), 124.0 (s), 130.0 (s), 130.3 (2ꢁ
d), 135.9 (2ꢁ s), 136.8 (s), 137.2 (s), 142.4 (dd, JCeF¼2.0 Hz), 157.6 (d,
JCeF¼243.5 Hz), 159.3 (s), 164.7 (s). Anal. Calcd for C22H22FNO3: C,
71.92; H, 6.04; N, 3.81. Found: C, 71.92; H, 6.16; N, 3.78.
4.1.11. 6-Chloro-3-ethoxycarbonylquinolin-2(1H)-one
needles; mp 276e277 ꢀC (ethyl acetateehexane); IR (KBr) 1685,
1555, 1480, 1290, 1195 cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
1.29 (t,
2i. White
d
4.1.6. 3-Ethoxycarbonyl-6-methoxycarbonyl-1-(2,4,6-
J¼7.1 Hz, 3H, CH3), 4.27 (q, J¼7.1 Hz, 2H, OCH2), 7.33 (d, J¼8.8 Hz,1H,
trimethylbenzyl)quinolin-2(1H)-one
209e210 ꢀC (ethyl acetateehexane); IR (KBr) 1715, 1670, 1625,
1300, 1210 cmꢂ1; 1H NMR (400 MHz, CDCl3)
2d. White
crystals;
mp
ArH), 7.64 (dd, J¼8.8, 2.4 Hz,1H, ArH), 7.95 (d, J¼2.4 Hz,1H, ArH), 8.45
(s,1H, CH),12.17 (brs,1H, NH); 13C NMR (100.6 MHz, DMSO-d6)
d 14.1
(q), 60.9 (t), 117.0 (d),118.8 (s),124.7 (s),126.0 (s), 128.2 (d),132.4 (d),
138.7 (s),142.3 (d),158.2 (s),164.2 (s); Anal. Calcd for C12H10ClNO3: C,
57.27; H, 4.01; N, 5.57. Found: C, 56.98; H, 4.08; N, 5.57.
d
1.44 (t, J¼7.2 Hz, 3H,
CH3), 2.18 (s, 6H, 2ꢁ CH3), 2.22 (s, 3H, CH3), 3.90 (s, 3H, OCH3), 4.44
(q, J¼7.2 Hz, 2H, OCH2), 5.67 (s, 2H, NCH2), 6.79 (s, 2H, ArH), 7.04 (d,
J¼9.0 Hz, 1H, ArH), 8.02 (dd, J¼9.0, 1.8 Hz, 1H, ArH), 8.32 (d,
J¼1.8 Hz, 1H, ArH), 8.44 (s, 1H, CH); 13C NMR (100.6 MHz, CDCl3)
4.1.12. 3-Ethoxycarbonyl-6-methylquinolin-2(1H)-one 2j. Light yel-
low needles; mp 183e184 ꢀC (ethyl acetateehexane); IR (KBr) 3150,
d
14.3 (q), 20.3 (2ꢁ q), 20.7 (q), 42.6 (t), 52.3 (q), 61.7 (t), 115.2 (d),
118.5 (s), 123.3 (s), 124.3 (s), 129.8 (s), 130.3 (2ꢁ d), 132.3 (d), 133.0
(d), 135.8 (2ꢁ s), 136.9 (s), 143.3 (s), 143.7 (d), 159.6 (s), 164.4 (s),
165.7 (s) ppm; Anal. Calcd for C24H25NO5: C, 70.74; H, 6.18; N, 3.44.
Found: C, 70.77; H, 6.21; N, 3.40.
1695, 1650, 1290, 1260 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 1.45 (t,
J¼7.1 Hz, 3H, CH3), 2.43 (s, 3H, CH3), 4.45 (q, J¼7.1 Hz, 2H, OCH2),
7.38 (d, J¼8.9 Hz, 1H, ArH), 7.41e7.45 (m, 2H, ArH), 8.51 (s, 1H, CH),
12.20 (brs, 1H, NH); 13C NMR (100.6 MHz, CDCl3)
d 14.2 (q), 20.7 (q),
61.2 (t), 116.2 (d), 118.4 (s), 121.7 (s), 128.3 (d), 132.5 (s), 134.5 (d),
138.1 (s), 145.3 (d), 161.4 (s), 164.5 (s); Anal. Calcd for C13H13NO3: C,
67.52; H, 5.67; N, 6.06. Found: C, 67.43; H, 5.71; N, 6.04.
4.1.7. 3-Ethoxycarbonyl-6-methyl-1-(2,4,6-trimethylbenzyl)quinolin-
2(1H)-one 2e. Light yellow needles; mp 114e115 ꢀC (ethyl aceta-
teehexane); IR (KBr) 1700, 1655, 1570, 1300, 1225 cmꢂ1 1H NMR
;
(400 MHz, CDCl3)
d
1.43 (t, J¼7.1 Hz, 3H, CH3), 2.17 (s, 6H, 2ꢁCH3),
4.1.13. 3-Ethoxycarbonyl-6,7-dimethylquinolin-2(1H)-one
2k. White needles; mp 241e242 ꢀC (ethyl acetateehexane); IR
(KBr) 1730, 1645, 1480, 1220, 1080 cmꢂ1; 1H NMR (400 MHz, CDCl3)
2.22 (s, 3H, CH3), 2.34 (s, 3H, CH3), 4.43 (q, J¼7.1 Hz, 2H, OCH2), 5.65
(s, 2H, NCH2), 6.78 (s, 2H, ArH), 6.90 (d, J¼8.7 Hz, 1H, ArH), 7.21 (dd,
J¼8.7, 2.1 Hz, 1H, ArH), 7.39 (s, 1H, ArH), 8.34 (s, 1H, CH); 13C NMR
d
1.46 (t, J¼7.1 Hz, 3H, CH3), 2.33 (s, 3H, CH3), 2.39 (s, 3H, CH3), 4.45
(q, J¼7.1 Hz, 2H, OCH2), 7.23 (s,1H, ArH), 7.39 (s,1H, ArH), 8.51 (s,1H,
CH), 11.91 (brs, 1H, NH); 13C NMR (100.6 MHz, CDCl3)
14.3 (q), 19.3
(100.6 MHz, CDCl3)
d
14.3 (q), 20.3 (2ꢁ q), 20.4 (q), 20.7 (q), 42.4 (t),
61.5 (t),115.0 (d),119.1 (s),122.4 (s),129.9 (d),130.2 (2ꢁ d),130.4 (s),
132.0 (s), 134.0 (d), 135.9 (2ꢁ s), 136.5 (s), 138.7 (s), 143.6 (d), 159.6
(s), 165.1 (s); Anal. Calcd for C23H25NO3: C, 76.01; H, 6.93; N, 3.85.
Found: C, 76.02; H, 6.93; N, 3.85.
d
(q), 20.5 (q), 61.3 (t), 116.4 (d), 116.9 (s), 120.7 (s), 128.9 (d), 132.3 (s),
138.7 (s), 143.9 (s), 145.5 (d), 161.2 (s), 164.8 (s); Anal. Calcd for
C14H15NO3: C, 68.56; H, 6.16; N, 5.71. Found: C, 68.40; H, 6.18; N, 5.70.
4.1.8. 3-Ethoxycarbonyl-6,7-dimethyl-1-(2,4,6-trimethylbenzyl)qui-
nolin-2(1H)-one 2f. White needles; mp 141e142 ꢀC (ethyl
4.1.14. 3-Acetyl-1-(2,4,6-trimethylbenzyl)quinolin-2(1H)-one
2l. Light yellow needles; mp 196e197 ꢀC (ethyl acetateehexane);

G.-A. Lin, C.-P. Chuang / Tetrahedron 71 (2015) 4795e4800
4799
IR (KBr) 1675, 1645, 1560, 1445, 1215 cmꢂ1
CDCl3)
;
1H NMR (400 MHz,
(s), 114.8 (s), 117.2 (d), 119.7 (s), 128.86 (s), 128.89 (d), 129.1 (s), 130.5
(2ꢁ d), 133.8 (d), 135.8 (2ꢁ s), 137.4 (s), 138.9 (s), 146.3 (d), 159.0 (s);
Anal. Calcd for C20H17ClN2O: C, 71.32; H, 5.09; N, 8.32. Found: C,
71.34; H, 5.15; N, 8.26.
d
2.18 (s, 6H, 2ꢁ CH3), 2.23 (s, 3H, CH3), 2.80 (s, 3H, CH3), 5.67
(s, 2H, NCH2), 6.80 (s, 2H, ArH), 7.01 (d, J¼8.6 Hz, 1H, ArH), 7.17 (t,
J¼7.5 Hz, 1H, ArH), 7.40 (ddd, J¼8.6, 7.5, 1.5 Hz, 1H, ArH), 7.66 (dd,
J¼7.5, 1.5 Hz, 1H, ArH), 8.40 (s, 1H, CH); 13C NMR (100.6 MHz, CDCl3)
d
20.2 (2ꢁ q), 20.7 (q), 31.0 (q), 42.3 (t), 115.1 (d), 119.5 (s), 122.6 (d),
4.1.20. 3-Benzoyl-1-(2,4,6-trimethylbꢀenzyl)quinolin-2(1H)-one
128.9 (s), 130.1 (s), 130.3 (2ꢁ d), 131.1 (d), 132.8 (d), 135.8 (2ꢁ s),
2r. Light yellow needles; mp 201e202 C (ethyl acetateehexane);
136.6 (s), 140.9 (s), 142.9 (d), 161.4 (s), 198.6 (s); Anal. Calcd for
IR (KBr) 1660, 1645, 1565, 1455, 1215 cmꢂ1 1H NMR (400 MHz,
;
C
4.35.
21H21NO2: C, 78.97; H, 6.63; N, 4.39. Found: C, 78.91; H, 6.66; N,
CDCl3)
d
2.24 (s, 9H, 3ꢁ CH3), 5.65 (s, 2H, NCH2), 6.81 (s, 2H, ArH),
7.06 (d, J¼7.9 Hz, 1H, ArH), 7.19 (t, J¼7.9 Hz, 1H, ArH), 7.40 (t,
J¼7.9 Hz, 1H, ArH), 7.46 (t, J¼7.7 Hz, 2H, ArH), 7.59 (t, J¼7.7 Hz, 1H,
ArH), 7.62 (d, J¼7.9 Hz, 1H, ArH), 7.88 (d, J¼7.7 Hz, 2H, ArH), 8.01 (s,
4.1.15. 3-Acetyl-6-methyl-1-(2,4,6-trimethylbenzyl)quinolin-2(1H)-
one 2m. Yellow crystals; mp 206e207 ꢀC (ethyl acetateehexane);
1H, CH); 13C NMR (100.6 MHz, CDCl3)
d
20.3 (2ꢁ q), 20.7 (q), 42.3
IR (KBr) 1675, 1645, 1565, 1350, 1225 cmꢂ1
;
1H NMR (400 MHz,
(t),115.3 (d), 119.8 (s), 122.6 (d), 128.4 (2ꢁ d), 129.4 (2ꢁ d), 130.0 (d),
130.22 (s), 130.26 (2ꢁ d), 131.4 (s), 131.9 (d), 133.3 (d), 135.9 (2ꢁ s),
136.7 (s),137.2 (s),140.2 (s),140.6 (d),160.7 (s),194.3 (s); Anal. Calcd
for C26H23NO2: C, 81.86; H, 6.08; N, 3.67. Found: C, 81.97; H, 6.08; N,
3.63.
CDCl3)
d
2.17 (s, 6H, 2ꢁ CH3), 2.23 (s, 3H, CH3), 2.34 (s, 3H, CH3), 2.79
(s, 3H, CH3), 5.65 (s, 2H, NCH2), 6.79 (s, 2H, ArH), 6.91 (d, J¼8.7 Hz,
1H, ArH), 7.22 (dd, J¼8.7, 1.6 Hz, 1H, ArH), 7.43 (s, 1H, ArH), 8.34 (s,
1H, CH); 13C NMR (100.6 MHz, CDCl3)
d
20.2 (2ꢁ q), 20.4 (q), 20.7
(q), 31.1 (q), 42.3 (t), 115.0 (d), 119.5 (s), 128.9 (s), 130.27 (2ꢁ d),
130.28 (s), 130.6 (d), 132.2 (s), 134.3 (d), 135.8 (2ꢁ s), 136.6 (s), 139.0
(s),142.7 (d),161.3 (s),198.8 (s); Anal. Calcd for C22H23NO2: C, 79.25;
H, 6.95; N, 4.20. Found: C, 79.24; H, 6.96; N, 4.20.
4.1.21. 3-Benzoyl-6-chloro-1-(2,4,6-trimethylbenzyl)quinolin-2(1H)-
one 2s. White needles; mp 253e254 ꢀC (ethyl acetateehexane); IR
(KBr) 1675, 1645, 1485, 1285, 1215 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
2.25 (s, 6H, 2ꢁ CH3), 2.26 (s, 3H, CH3), 5.65 (s, 2H, NCH2), 6.84 (s,
4.1.16. 3-Acetyl-6-chloro-1-(2,4,6-trimethylbenzyl)quinolin-2(1H)-
2H, ArH), 7.02 (d, J¼9.1 Hz, 1H, ArH), 7.36 (dd, J¼9.1, 2.3 Hz, 1H,
ArH), 7.49 (t, J¼7.5 Hz, 2H, ArH), 7.60 (d, J¼2.3 Hz, 1H, ArH), 7.62 (t,
one 2n. Light yellow needles; mp 204e205 ꢀC (ethyl aceta-
teehexane); IR (KBr) 1680, 1655, 1560, 1485, 1210 cmꢂ1
;
1H NMR
J¼7.5 Hz, 1H, ArH), 7.89 (d, J¼7.5 Hz, 2H, ArH), 7.92 (s, 1H, CH); 13
C
(400 MHz, CDCl3)
d
2.17 (s, 6H, 2ꢁ CH3), 2.23 (s, 3H, CH3), 2.78 (s,
NMR (100.6 MHz, CDCl3)
d
20.3 (2ꢁ q), 20.7 (q), 42.4 (t), 116.7 (d),
3H, CH3), 5.65 (s, 2H, NCH2), 6.81 (s, 2H, ArH), 6.94 (d, J¼9.1 Hz, 1H,
ArH), 7.33 (dd, J¼9.1, 2.4 Hz, 1H, ArH), 7.62 (d, J¼2.4 Hz, 1H, ArH),
120.8 (s), 128.1 (s), 128.5 (2ꢁ d), 128.8 (d), 129.4 (2ꢁ d), 129.9 (s),
130.4 (2ꢁ d), 131.8 (d), 132.6 (s), 133.5 (d), 135.9 (2ꢁ s), 136.8 (s),
137.0 (s), 138.6 (s), 139.1 (d), 160.3 (s), 193.8 (s); Anal. Calcd for
8.28 (s, 1H, CH); 13C NMR (100.6 MHz, CDCl3)
d
20.2 (2ꢁ q), 20.7 (q),
31.0 (q), 42.4 (t), 116.6 (d), 120.5 (s), 128.1 (s), 129.7 (d), 129.8 (s),
130.0 (s), 130.4 (2ꢁ d), 132.7 (d), 135.8 (2ꢁ s), 136.9 (s), 139.3 (s),
141.4 (d), 161.0 (s), 198.2 (s); Anal. Calcd for C21H20ClNO2: C, 71.28;
H, 5.70; N, 3.96. Found: C, 71.21; H, 5.73; N, 3.90.
C26H22ClNO2: C, 75.08; H, 5.33; N, 3.37. Found: C, 75.04; H, 5.42; N,
3.37.
4.1.22. 3-Benzoyl-6-fluoro-1-(2,4,6-trimethylbenzyl)quinolin-2(1H)-
one 2t. White needles; mp 212e213 ꢀC (ethyl acetateehexane); IR
(KBr) 1670, 1645, 1575, 1440, 1235 cmꢂ1; 1H NMR (400 MHz, CDCl3)
4.1.17. 3-Cyano-1-(2,4,6-trimethylbenzyl)quinolin-2(1H)-one
2o. Light yellow crystals; mp 232e233 ꢀC (ethyl acetateehexane);
d
2.23 (s, 6H, 2ꢁ CH3), 2.24 (s, 3H, CH3), 5.64 (s, 2H, NCH2), 6.82 (s,
IR (KBr) 2230, 1645, 1590, 1565, 1455 cmꢂ1
;
1H NMR (400 MHz,
2H, ArH), 7.03 (dd, J¼9.4, 4.3 Hz, 1H, ArH), 7.13 (ddd, J¼9.4, 8.0,
2.9 Hz, 1H, ArH), 7.28 (dd, J¼8.0, 2.9 Hz, 1H, ArH), 7.46 (t, J¼7.6 Hz,
2H, ArH), 7.59 (t, J¼7.6 Hz, 1H, ArH), 7.87 (d, J¼7.6 Hz, 2H, ArH), 7.91
CDCl3)
d
2.19 (s, 6H, 2ꢁCH3), 2.23 (s, 3H, CH3), 5.65 (s, 2H, NCH2),
6.81 (s, 2H, ArH), 7.07 (d, J¼8.6 Hz, 1H, ArH), 7.23 (t, J¼7.5 Hz, 1H,
ArH), 7.47 (ddd, J¼8.6, 7.5, 1.4 Hz, 1H, ArH), 7.60 (dd, J¼7.5, 1.4 Hz,
(s, 1H, CH); 13C NMR (100.6 MHz, CDCl3)
d
20.3 (2ꢁ q), 20.7 (q), 42.5
1H, ArH), 8.23 (s, 1H, CH); 13C NMR (100.6 MHz, CDCl3)
d
20.3 (2ꢁ
(t), 114.5 (dd, JCeF¼22.1 Hz), 117.0 (dd, JCeF¼8.0 Hz), 119.8 (dd,
JCeF¼24.1 Hz), 120.6 (d, JCeF¼8.0 Hz), 128.5 (2ꢁ d), 129.4 (2ꢁ d),
130.0 (s), 130.3 (2ꢁ d), 132.8 (s), 133.5 (d), 135.9 (2ꢁ s), 136.7 (s),
136.8 (s), 136.9 (s), 139.2 (dd, JCeF¼3.0 Hz), 157.7 (d, JCeF¼244.5 Hz),
160.3 (s), 193.9 (s); Anal. Calcd for C26H22FNO2: C, 78.18; H, 5.55; N,
3.51. Found: C, 78.06; H, 5.59; N, 3.48.
q), 20.7 (q), 43.1 (t), 106.9 (s), 115.3 (s), 115.6 (d), 118.9 (s), 123.2 (d),
129.4 (s), 130.2 (d), 130.4 (2ꢁ d), 133.9 (d), 135.9 (2ꢁ s), 137.0 (s),
140.6 (s), 147.6 (d), 159.4 (s); Anal. Calcd for C20H18N2O: C, 79.44; H,
6.00; N, 9.26. Found: C, 79.33; H, 6.01; N, 9.29.
4.1.18. 3-Cyano-6-methyl-1-(2,4,6-trimethylbenzyl)quinolin-2(1H)-
one 2p. Light yellow needles; mp 215e216 ꢀC (ethyl aceta-
4.1.23. 3-Benzoyl-6-methyl-1-(2,4,6-trimethylbenzyl)quinolin-
teehexane); IR (KBr) 2230, 1655, 1570, 1500, 1230 cmꢂ1
;
1H NMR
2(1H)-one 2u. White needles; mp 231e232 ꢀC (ethyl aceta-
(400 MHz, CDCl3)
d
2.18 (s, 6H, 2ꢁ CH3), 2.23 (s, 3H, CH3), 2.35 (s,
teehexane); IR (KBr) 1675, 1645, 1570, 1445, 1235 cmꢂ1 1H NMR
;
3H, CH3), 5.63 (s, 2H, NCH2), 6.80 (s, 2H, ArH), 6.96 (d, J¼8.8 Hz, 1H,
ArH), 7.29 (dd, J¼8.8, 1.9 Hz, 1H, ArH), 7.37 (s, 1H, ArH), 8.16 (s, 1H,
(400 MHz, CDCl3)
d
2.23 (s, 9H, 3ꢁ CH3), 2.35 (s, 3H, CH3), 5.63 (s,
2H, NCH2), 6.81 (s, 2H, ArH), 6.96 (d, J¼8.7 Hz, 1H, ArH), 7.22 (dd,
J¼8.7, 1.9 Hz, 1H, ArH), 7.39 (s, 1H, ArH), 7.45 (t, J¼7.6 Hz, 2H, ArH),
7.58 (t, J¼7.6 Hz, 1H, ArH), 7.87 (d, J¼7.6 Hz, 2H, ArH), 7.95 (s, 1H,
CH); 13C NMR (100.6 MHz, CDCl3)
d
20.3 (2ꢁ q), 20.4 (q), 20.7 (q),
43.0 (t), 106.7 (s), 115.47 (s), 115.51 (d), 118.9 (s), 129.6 (s), 129.7 (d),
130.3 (2ꢁ d), 133.0 (s), 135.3 (d), 135.9 (2ꢁ s), 137.0 (s), 138.7 (s),
147.4 (d), 159.4 (s); Anal. Calcd for C21H20N2O: C, 79.92; H, 6.37; N,
8.85. Found: C, 79.65; H, 6.37; N, 8.81.
CH); 13C NMR (100.6 MHz, CDCl3)
d
20.3 (2ꢁ q), 20.4 (q), 20.7 (q),
42.3 (t), 115.1 (d), 119.8 (s), 128.4 (2ꢁ d), 129.4 (2ꢁ d), 129.6 (d),
130.2 (2ꢁ d), 130.4 (s), 131.3 (s), 132.2 (s), 133.2 (d), 133.3 (d), 135.9
(2ꢁ s), 136.6 (s), 137.3 (s), 138.3 (s), 140.5 (d), 160.6 (s), 194.5 (s);
Anal. Calcd for C27H25NO2: C, 82.00; H, 6.37; N, 3.54. Found: C,
81.87; H, 6.36; N, 3.50.
4.1.19. 6-Chloro-3-cyano-1-(2,4,6-trimethylbenzyl)quinolin-2(1H)-
one 2q. Light yellow needles (ethyl acetateeheꢂx1ane); mp
221e222 ꢀC; IR (KBr) 2230, 1655, 1560, 1420, 1210 cm
;
1H NMR
(400 MHz, CDCl3)
d
2.17 (s, 6H, 2ꢁ CH3), 2.23 (s, 3H, CH3), 5.62 (s,
4.1.24. 3-Benzoyl-6,7-dimethyl-1-(2,4,6-trimethylbenzyl)quinolin-
2H, NCH2), 6.81 (s, 2H, ArH), 7.00 (d, J¼9.1 Hz, 1H, ArH), 7.40 (dd,
2(1H)-one 2v. White needles; mp 249e250 ꢀC (ethyl aceta-
J¼9.1, 2.2 Hz, 1H, ArH), 7.57 (d, J¼2.2 Hz, 1H, ArH), 8.14 (s, 1H, CH);
teehexane); IR (KBr) 1640, 1595, 1555, 1455, 1240 cmꢂ1 1H NMR
;
(400 MHz, CDCl3) d 2.20 (s, 3H, CH3), 2.23 (s, 3H, CH3), 2.25 (s, 3H,
13C NMR (100.6 MHz, CDCl3)
d
20.3 (2ꢁ q), 20.7 (q), 43.2 (t), 108.2

4800
G.-A. Lin, C.-P. Chuang / Tetrahedron 71 (2015) 4795e4800
4. (a) Citterio, A.; Sebastiano, R.; Marion, A. J. Org. Chem. 1991, 56, 5328e5335; (b)
Citterio, A.; Sebastiano, R.; Nicolini, M. Tetrahedron 1993, 49, 7743e7760; (c)
Liao, Y.-J.; Wu, Y.-L.; Chuang, C.-P. Tetrahedron 2003, 59, 3511e3520.
CH3), 2.26 (s, 6H, 2ꢁ CH3), 5.61 (s, 2H, NCH2), 6.81 (s, 2H, ArH), 6.89
(s, 1H, ArH), 7.33 (s, 1H, ArH), 7.44 (t, J¼7.6 Hz, 2H, ArH), 7.56 (t,
J¼7.6 Hz, 1H, ArH), 7.86 (d, J¼7.6 Hz, 2H, ArH), 7.95 (s, 1H, CH); 13
C
5. (a) Wu, Y.-L.; Chuang, C.-P. Tetrahedron Lett. 2001, 42, 1717e1719; (b) Tsai, A.-I.;
Wu, Y.-L.; Chuang, C.-P. Tetrahedron 2001, 57, 7829e7837; (c) Tseng, C.-M.; Wu,
Y.-L.; Chuang, C.-P. Tetrahedron 2004, 60, 12249e12260; (d) Chen, H.-L.; Lin, C.-
Y.; Cheng, Y.-C.; Tsai, A.-I.; Chuang, C.-P. Synthesis 2005, 977e985; (e) Lin, C.-Y.;
Cheng, Y.-C.; Tsai, A.-I.; Chuang, C.-P. Org. Biomol. Chem. 2006, 4, 1097e1103.
6. (a) Patel, M.; McHugh, R. J., Jr.; Cordova, B. C.; Klabe, R. M.; Bacheler, L. T.;
Erickson-Viitanen, S.; Rodgers, J. D. Bioorg. Med. Chem. Lett. 2001, 11,
1943e1945; (b) Yong, S. R.; Ung, A. T.; Pyne, S. G.; Skelton, B. W.; White, A. H.
Tetrahedron 2007, 63, 1191e1199; (c) Ellis, D.; Kuhen, K. L.; Anaclerio, B.; Wu, B.;
Wolff, K.; Yin, H.; Bursulaya, B.; Caldwell, J.; Karanewsky, D.; He, Y. Bioorg. Med.
Chem. Lett. 2006, 16, 4246e4251; (d) Fujioka, T.; Teramoto, S.; Mori, T.; Hoso-
kawa, T.; Sumida, T.; Tominaga, M.; Yabuuchi, Y. J. Med. Chem. 1992, 35,
3607e3612; (e) Hayashi, H.; Miwa, Y.; Miki, I.; Ichikawa, S.; Yoda, N.; Ishii, A.;
Kono, M.; Suzuki, F. J. Med. Chem. 1992, 35, 4893e4902; (f) Angibaud, P. R.;
Venet, M. G.; Filliers, W.; Broeckx, R.; Ligny, Y. A.; Muller, P.; Poncelet, V. S.; End,
D. W. Eur. J. Org. Chem. 2004, 479e486; (g) Boy, K. M.; Guernon, J. M.; Sit, S.-Y.;
Xie, K.; Hewawasam, P.; Boissard, C. G.; Dworetzky, S. I.; Natale, J.; Gribkoff, V.
K.; Lodge, N.; Starret, J. E. Bioorg. Med. Chem. Lett. 2004, 14, 5089e5093.
7. (a) Jones, G. In Comprehensive Heterocyclic Chemistry; Boulton, A. J., Mckillop, A.,
Eds.; Pergamon: Oxford, UK, 1984; Vol. 2, Chapter 8; (b) Koltunov, K. Y.; Wal-
spurger, S.; Sommer, J. Chem. Commun. 2004, 1754e1755; (c) Li, K.; Foresee, L.
N.; Tunge, J. A. J. Org. Chem. 2005, 70, 2881e2883; (d) Sai, K. K. S.; Gilbert, T. M.;
NMR (100.6 MHz, CDCl3)
d
18.9 (q), 20.3 (2ꢁ q), 20.7 (q), 20.9 (q),
42.1 (t), 116.2 (d), 118.0 (s), 128.3 (2ꢁ d), 129.4 (2ꢁ d), 130.0 (d),
130.08 (s), 130.13 (2ꢁ d), 130.5 (s), 131.6 (s), 133.1 (d), 136.0 (2ꢁ s),
136.6 (s), 137.5 (s), 138.7 (s), 140.6 (d), 142.0 (s), 160.6 (s), 194.7 (s);
Anal. Calcd for C28H27NO2: C, 82.12; H, 6.65; N, 3.42. Found: C,
82.05; H, 6.64; N, 3.41.
4.1.25. 3-Benzoyl-6,8-dimethyl-1-(2,4,6-trimethylbenzyl)quinolin-
2(1H)-one 2w. Yellow crystals; mp 208e209 ꢀC (ethyl aceta-
teehexane); IR (KBr) 1655, 1565, 1445, 1275, 1235 cmꢂ1 1H NMR
;
(400 MHz, CDCl3)
3H, CH3), 2.68 (s, 3H, CH3), 5.36 (s, 2H, NCH2), 6.77 (s, 2H, ArH), 7.21
d
2.07 (s, 6H, 2ꢁ CH3), 2.26 (s, 3H, CH3), 2.40 (s,
(t, J¼7.8 Hz, 2H, ArH), 7.26 (s, 1H, ArH), 7.28 (s, 1H, ArH), 7.44 (t,
J¼7.8 Hz, 1H, ArH), 7.49 (d, J¼7.8 Hz, 2H, ArH), 7.83 (s, 1H, CH); 13
C
NMR (100.6 MHz, CDCl3)
d
20.29 (q), 20.32 (2ꢁ q), 20.8 (q), 23.2 (q),
49.9 (t), 121.6 (s), 124.7 (s), 128.0 (2ꢁ d), 128.2 (d), 129.4 (2ꢁ d),
129.6 (2ꢁ d),131.0 (s),131.7 (s),132.3 (s),132.9 (d),136.37 (s),136.43
(s), 136.9 (2ꢁ s), 137.9 (d), 141.1 (d), 141.6 (s), 162.1 (s), 194.0 (s);
Anal. Calcd for C28H27NO2: C, 82.12; H, 6.65; N, 3.42. Found C:
82.00; H, 6.68; N, 3.35.
ꢀ
Klumpp, D. A. J. Org. Chem. 2007, 72, 9761e9764; (e) Domínguez-Fernandez, F.;
ꢀ
ꢀ
ꢀ
Lopez-Sanz, J.; Perez-Mayoral, E.; Bek, D.; Martín-Aranda, R. M.; Lopez-Peinado,
ꢁ
A. J.; Cejka, J. ChemCatChem 2009, 1, 241e243.
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2829e2832; (b) Binot, G.; Zard, S. Z. Tetrahedron Lett. 2005, 46, 7503e7506; (c)
Zhou, W.; Zhang, L.; Jiao, N. Tetrahedron 2009, 65, 1982e1987; (d) Tsubusaki, T.;
Nishino, H. Tetrahedron 2009, 55, 9448e9459.
9. (a) Lee, C. G.; Lee, K. Y.; Lee, S.; Kim, J. N. Tetrahedron Lett. 2005, 46, 1493e1499;
(b) Familonni, O. B.; Klaas, P. J.; Lobb, K. A.; Pakade, V. E.; Kaye, P. T. Org. Biomol.
Chem. 2006, 4, 3960e3965; (c) Pathak, R.; Madapa, S.; Batra, S. Tetrahedron
2007, 63, 451e460.
10. Okuro, K.; Kai, H.; Alper, H. Tetrahedron: Asymmetry 1997, 8, 2307e2309.
11. (a) Berrino, R.; Cacchi, S.; Fabrizi, G.; Goggiamani, A. J. Org. Chem. 2012, 77,
2881e2883; (b) Berrino, R.; Cacchi, S.; De Salve, I.; Fabrizi, G. Synlett 2006,
2947e2952; (c) Inamoto, K.; Kawasaki, J.; Hiroya, K.; Kondo, Y.; Doi, T. Chem.
Commun. 2012, 4332e4334.
Acknowledgements
We are grateful to the National Science Council Taiwan for fi-
nancial support. (Grant No. NSCe100e2113eMe006e009eMY2).
Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2015.05.043.
12. Fujita, K.-i.; Takahashi, Y.; Owaki, M.; Yamamoto, K.; Yamaguchi, R. Org. Lett.
2004, 6, 2785e2788.
13. Horn, J.; Li, H. Y.; Marsden, S. P.; Nelson, A.; Shearer, R. J.; Campbell, A. J.; House,
D.; Weingarten, G. G. Tetrahedron 2009, 65, 9002e9007.
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Chuang, C.-P.; Lin, P.-Y. Tetrahedron 2001, 57, 5543e5549; (c) Tseng, C.-C.; Wu,
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References and notes
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