An efficient synthesis of 2-hydroxy-7,8-dihydroquinolin-5(6H)-ones and 7,8-dihydroquinoline-2,5(1H,6H)-diones from Morita-Baylis-Hillman adduct acetates

Article abstract of DOI:10.1055/s-2008-1078601

A series of 2-hydroxy-7,8-dihydroquinolin-5(6H)-ones and 7,8-dihydroquinoline-2,5(1H,6H)-diones have been synthesized in good to excellent yields from Morita-Baylis-Hillman adduct acetates, cyclohexane-1,3-diones and ammonium acetate or primary amines in one pot under solvent-free conditions. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1078601

PAPER
2561
An Efficient Synthesis of 2-Hydroxy-7,8-dihydroquinolin-5(6H)-ones and
7,8-Dihydroquinoline-2,5(1H,6H)-diones from Morita–Baylis–Hillman
Adduct Acetates
2
-Hydroxy-7,8-dihydroq
e
uinolin-5(
6
i
H
)-one
h
s
and 7,8-D
i
u
hydroquinol
i
ine-2,5(1
H
,6
H
Z
)-dione
s
hong, Fuliang Lin, Ren’er Chen, Weike Su*
College of Pharmaceutical Sciences, Zhejiang University of Technology, Zhejiang Key Laboratory of Pharmaceutical Engineering,
Hangzhou 310014, P. R. of China
Fax +86(571)88320752; E-mail: suweike@zjut.edu.cn
Received 28 February 2008; revised 7 May 2008
Recently, a direct conversion of Morita–Baylis–Hillman
adduct acetates into 3-substituted 7,8-dihydro-6H-
chromene-2,5-diones 3 in excellent isolated yields under
solvent-free conditions has been successfully achieved in
our laboratory.14 It occurred to us that we should be able
to synthesize the target compounds 4 and 6 in a one-pot,
three-component process under solvent-free conditions.
Our synthetic rationale is described in Scheme 1.
Abstract: A series of 2-hydroxy-7,8-dihydroquinolin-5(6H)-ones
and 7,8-dihydroquinoline-2,5(1H,6H)-diones have been synthe-
sized in good to excellent yields from Morita–Baylis–Hillman
adduct acetates, cyclohexane-1,3-diones and ammonium acetate or
primary amines in one pot under solvent-free conditions.
Key words: 2-hydroxy-7,8-dihydroquinolin-5(6H)-ones, 7,8-dihy-
droquinoline-2,5(1H,6H)-diones, Morita–Baylis–Hillman adduct
acetates, cyclohexane-1,3-diones, solvent-free conditions
O
O
O
Nitrogen- and oxygen-containing heterocycles, such as
carbostyrils, dihydroquinolinones and quinoline deriva-
tives, are important core structures in organic chemistry
because of their presence in many natural products1,2a and
their various biological activity,2 such as antitumor,3 an-
tipsychotic,4 antibacterial,5 cardiac6 and cytotoxic activi-
ties.7
OAc
O
R1
O
R3 R3
2
R1
OR2
Et3N
solvent-free
R3
R3
1
O
2a R3 = Me
2b R3 = H
NH4OAc
R1 = aryl, heteroaryl
2 = Me, Et
3
R
R4NH2
During the last decade, the applications of Morita–Baylis–
Hillman adducts have attracted considerable interest.8 The
Morita–Baylis–Hillman reaction has been approved as an
atom-economical, environment-friendly, carbon–carbon
bond-forming reaction providing densely functionalized
molecules whose applications in many organic transfor-
mation methodologies have been well documented.9,10
Several reports on the preparation of dihydroquinolinones
have been published.11,12 Kim and co-workers13 reported
that 3-benzyl-7,8-dihydroquinolin-5(6H)-ones can be ob-
tained from Morita–Baylis–Hillman adducts and 3-ami-
nocyclohex-2-enone in butan-1-ol upon refluxing for 18
hours, followed by treatment with DBU; however, this
method has several drawbacks, including harsh reaction
conditions, low reaction efficiency and low chemoselec-
tivity. Therefore, developing efficient, ‘green’ and conve-
nient methodologies for the synthesis of dihydro-
quinolinones is still of interest and highly desirable.
5
OH
O
R4
R1
4 = aryl, alkyl, heteroaryl
N
R1
N
R
R3
R3
4 (75–91%)
R3
R3
O
O
6 (73–87%)
Scheme 1
Firstly, a three-component reaction of the Morita–Baylis–
Hillman adduct acetate 1a (R1 = Ph, R2 = Me), 5,5-di-
methylcyclohexane-1,3-dione (2a) and ammonium ace-
tate was carried out in one pot using triethylamine as base
under solvent-free conditions at 90 °C for 12 hours. Un-
fortunately, the desired product 4a was obtained in only
35% yield. Thus, we changed the method and first carried
out reaction of a mixture of the Morita–Baylis–Hillman
adduct acetate 1a, 5,5-dimethylcyclohexane-1,3-dione
(2a) and triethylamine under solvent-free conditions at 90
°C. TLC showed that the starting material 1a was con-
sumed within three hours to produce the intermediate 3-
benzyl-7,7-dimethyl-7,8-dihydro-6H-chromene-2,5-di-
one (3a).14 Then, ammonium acetate was added to the
above mixture and the reaction was further stirred for one
hour. After the mixture was cooled to 0 °C, the reaction
was quenched with a solution of ethanol–water (4:1) and,
In our ongoing studies on the application of Morita–
Baylis–Hillman adduct acetates for the construction of
oxygen- and nitrogen-fused heterocycles, we wish to re-
port a new methodology for the synthesis of 2-hydroxy-
7,8-dihydroquinolin-5(6H)-ones 4 and 7,8-dihydroquino-
line-2,5(1H,6H)-diones 6 under solvent-free conditions.
SYNTHESIS 2008, No. 16, pp 2561–2568
x
x.
x
x
.
2
0
0
8
Advanced online publication: 17.07.2008
DOI: 10.1055/s-2008-1078601; Art ID: F04508SS
© Georg Thieme Verlag Stuttgart · New York

2562
W. Zhong et al.
PAPER
Table 1 Synthesis of 2-Hydroxy-7,8-dihydroquinolin-5(6H)-ones 4
from Morita–Baylis–Hillman Adduct Acetates 1a
finally, 3-benzyl-2-hydroxy-7,7-dimethyl-7,8-dihydro-
quinolin-5(6H)-one (4a) was isolated in 82% yield
(Scheme 2). More importantly, the workup procedure is
very convenient, and the products can be isolated by sim-
ple filtration and washed with commercially available eth-
anol. Our protocol avoids the use of toxic organic solvents
during the reaction and isolation process, and thus is supe-
rior to the previous methods.13
Entry R1
R2
R3
Timeb
(h)
ProductYieldc
(%)
1
2
Ph
Me
Et
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
H
3.5 (1)
4.5 (1)
3.5 (1)
3.0 (1)
3.5 (1)
3.0 (1)
3.5 (1)
6.5 (1)
4.5 (1)
7.0 (1)
4.5 (1)
3.5 (1)
3.5 (1)
3.0 (1)
3.5 (1)
4.0 (1)
4a
4a
4a
4b
4c
4d
4e
4f
82
75
73d
91
85
88
87
75
83
Ph
3
Ph
Me
Me
Me
Me
Me
Me
Me
Me
OH
OAc
O
4
3-O2NC6H4
2-ClC6H4
2-Cl-6-FC6H3
4-FC6H4
furan-2-yl
thien-2-yl
3,4-Me2C6H3
(1) 2, Et3N, 90 °C
R1
N
R1
OR2
5
(2) NH4OAc, 90 °C
6
R3
R3
O
7
1a R1 = Ph, R2 = Me
1b R1 = 3-O2NC6H4, R2 = Me
4a R3 = Me; 82%
4b R3 = Me; 91%
8
Scheme 2
9
4g
10
11
12
13
14
15
16
4h, 4h¢ 80e
Encouraged by these results and the workup operation,
and with a view to understanding the generality of this re-
action, we successfully extended the same strategy to a se-
ries of Morita–Baylis–Hillman adduct acetates; the results
are summarized in Table 1. The reaction was compatible
with a variety of Morita–Baylis–Hillman adduct acetates
1 with electron-donating or electron-withdrawing groups
on the aromatic ring. The substrates with electron-donat-
ing groups afforded much lower yields and needed longer
reaction times than those with electron-withdrawing
groups. Heterocyclic compounds could also afford the
corresponding products 4f, 4g in high yield. On the other
hand, an ethyl ester in substrates 1 gives a lower yield than
that of the methyl ester; steric effects may play an impor-
tant role and resulted in moderate yield of the product
(Table 1, entry 2).
3,4-(OCH2O)C6H3 Me
4i
80
79
85
90
82
78
3-MeOC6H4
4-FC6H4
Me
Me
Me
Me
Me
4j
4k
4l
3-O2NC6H4
Ph
H
H
4m
3-MeOC6H4
H
4n
a All reactions were carried out on Morita–Baylis–Hillman adduct
acetates (1 mmol) with cyclic b-diketones (1.2 mmol) in the presence
of triethylamine (1.2 mmol) at 90 °C under solvent-free conditions;
ammonium acetate (3 mmol) was added subsequently.
b Reaction times for step 1 and step 2 (in brackets).
c Isolated yields based on the Morita–Baylis–Hillman adduct acetates.
d Ammonia was used instead of ammonium acetate.
e Isolated total yield.
Interestingly, when the Morita–Baylis–Hillman adduct
acetate 1h was used as the substrate (Scheme 3), the unex-
pected mixed products 4h and 4h¢ were obtained (Table 1,
entry 10), in a ratio of about 1:3, which have been identi-
fied by 1H and 13C NMR spectroscopy and MS data. How-
ever, when the Morita–Baylis–Hillman adduct acetate 1o,
derived from pentanal and methyl acrylate, was used as
the substrate, the unexpected exclusive product 4o was
obtained by a three-component reaction in 55% yield
(Scheme 4), even though the intermediate 3o has never
been detected or isolated during the reaction,14 which can-
not be explained at this stage.
O
O
OAc
O
O
OMe
O
2a
Et3N, 90 °C
1h
O
3h
O
OH
N
NH
NH4OAc
90 °C
+
With the above optimized reaction conditions, we
synthesized the 3-(arylmethyl)-7,8-dihydroquinoline-
2,5(1H,6H)-diones 6 via treatment with a series of prima-
ry amines 5 (Scheme 1). The reactions were also efficient
and afforded the desired products in good yields; the re-
sults are summarized in Table 2. It can be seen that the re-
action afforded the product in good yield when the
reaction time in step 2 was extended; moreover, the pri-
mary amines 5 with electron-withdrawing groups re-
quired a much longer reaction time in step 2.
O
O
4h
4h'
1:3
Scheme 3
According to all of these results, a possible mechanism for
the formation of compounds 4 (except for 4o) and 6 from
Morita–Baylis–Hillman adduct acetates 1 can be illustrat-
ed as shown in Scheme 5. A possible mechanism for the
formation of compound 4o can be described as per
Scheme 6.
Synthesis 2008, No. 16, 2561–2568 © Thieme Stuttgart · New York

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2-Hydroxy-7,8-dihydroquinolin-5(6H)-ones and 7,8-Dihydroquinoline-2,5(1H,6H)-diones
2563
O
OAc
O
2a, Et3N, NH4OAc
NH
OMe
90 °C
55%
1o
O
4o
2a, Et3N, 90 °C
O
O
NH4OAc
O
3o
Scheme 4
Table 2 Synthesis of 7,8-Dihydroquinoline-2,5(1H,6H)-diones 6 from Morita–Baylis–Hillman Adduct Acetates 1a
Entry
R1
R2
R3
R4 of Amine 5
n-Bu
Timeb (h)
3.0 (3)
3.0 (2)
3.0 (2)
3.0 (1)
3.0 (3)
3.0 (3)
3.0 (2)
Product
6a
Yieldc (%)
1
2
3
4
5
6
7
4-FC6H4
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
85
83
85
87
81
73
82
3-O2NC6H4
3-O2NC6H4
3-O2NC6H4
3-O2NC6H4
3-O2NC6H4
3-O2NC6H4
Ph
6b
4-Tol
6c
4-MeOC6H4
4-ClC6H4
3,4-F2C6H3
4-phenylthiazol-2-yl
6d
6e
6f
6g
a All reactions were carried out on Morita–Baylis–Hillman adduct acetates (1 mmol) with 5,5-dimethylcyclohexane-1,3-dione (2a; 1.2 mmol)
in the presence of triethylamine (1.2 mmol) at 90 °C under solvent-free conditions; an amine 5 (3 mmol) was added subsequently.
b Reaction times for step 1 and step 2 (in brackets).
c Isolated yields based on the Morita–Baylis–Hillman adduct acetates.
O
O
O
O
OAc
O
R1
O
R3
R3
– AcOH
R1
O
R1
OR2
OH
isomerization
R1
OR2
–
NEt3
R3
R3
R3
R3
O
O
O
1
2
O
R3
3
R3
O
O
Nu:
OH
O
O
R1
R1
O
NH2
R1
N
R1
NH
Nu = NH4OAc
R3
R1
NH
– H2O
OH
OH
R3
R3
R3
R3
R3
R3
R3
O
O
H+
O
O
O
O
O
R3
R3
H
3
4
R4
NH
O
R4
R4
R1
R1
N
– H2O
R1
OH
N
OH
Nu = R4NH2
R3
R3
R3
R3
R3
O
H+
O
O
R3
H
6
Scheme 5
Synthesis 2008, No. 16, 2561–2568 © Thieme Stuttgart · New York

2564
W. Zhong et al.
PAPER
O
O
,
NH2
O
O
NH2
O
OAc
O
NH2
OH
Et3N
OMe
OH
OMe
OH
OMe
NH4OAc
1o
H
O
O
O
NH3
NH2
O
NH2
O
H
O
O
H3N
NH
NH
NH
NH
OH
H
O
O
H
O
O
4o
Scheme 6
Anal. Calcd for C18H19NO2: C, 76.84; H, 6.81; N, 4.98. Found: C,
76.65; H, 6.64; N, 5.11.
In summary, we have developed a simple, efficient and
‘green’ strategy for the synthesis of various 7,8-dihydro-
quinolinones from Morita–Baylis–Hillman adduct ace-
tates, cyclic b-diketones and ammonium acetate or
primary amines in one pot under solvent-free conditions.
Merits of the present process are the simple experimental
procedure, especially the workup operation, environmen-
tal friendliness, and high yields and purity of products.
2-Hydroxy-7,7-dimethyl-3-(3-nitrobenzyl)-7,8-dihydroquino-
lin-5(6H)-one (4b)
White solid; mp 236.4–238.1 °C; Rf = 0.20 (hexane–EtOAc, 1:1).
IR (KBr): 3423, 3134, 1635, 1527, 1401, 1225 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 1.00 (s, 6 H, CH3), 2.32 (s, 2
H, CH2), 2.68 (s, 2 H, CH2), 3.87 (s, 2 H, CH2), 7.58 (t, J = 8.0 Hz,
1 H, ArH), 7.74 (t, J = 8.0 Hz, 2 H, ArH), 8.05–8.08 (m, 1 H, ArH),
8.15 (s, 1 H, ArH), 12.15 (br s, 1 H, OH).
13C NMR (100 MHz, DMSO-d6): d = 28.2 (2 C), 33.1, 35.2, 40.6,
50.5, 112.0, 121.7, 123.7, 130.0, 130.2, 134.5, 136.1, 142.7, 148.2,
154.7, 163.5, 193.9.
Starting materials and solvents were purchased from common com-
mercial sources and were used without additional purification.
Melting points were determined with a Büchi B-540 capillary melt-
ing point apparatus and are uncorrected. IR spectra were recorded
on a Nicolet Avatar-370 instrument. 1H and 13C NMR spectra were
recorded on Varian (400 MHz) and Avance III (500 MHz) instru-
ments using TMS as an internal standard. Mass spectra were mea-
sured with a Finnigan Trace DSQ instrument. Elemental analyses
were performed on a VarioEL-3 instrument. All spectroscopic data
of the products were identical to data from authentic samples.
MS (ESI): m/z (%) = 327 (100) [M+ + 1].
Anal. Calcd for C18H18N2O4: C, 66.25; H, 5.56; N, 8.58. Found: C,
65.99; H, 5.37; N, 8.60.
3-(2-Chlorobenzyl)-2-hydroxy-7,7-dimethyl-7,8-dihydroquino-
lin-5(6H)-one (4c)
3-(Arylmethyl)-2-hydroxy-7,8-dihydroquinolin-5(6H)-ones 4
and 3-(Arylmethyl)-7,8-dihydroquinoline-2,5(1H,6H)-diones 6;
General Procedure
White solid; mp 224.8–226.7 °C; Rf = 0.25 (hexane–EtOAc, 1:1).
IR (KBr): 3427, 3124, 1669, 1636, 1400, 1209 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.12 (s, 6 H, CH3), 2.39 (s, 2 H,
CH2), 2.76 (s, 2 H, CH2), 3.97 (s, 2 H, CH2), 7.16–7.20 (m, 2 H,
ArH), 7.31 (t, J = 5.0 Hz, 1 H, ArH), 7.35–7.38 (m, 1 H, ArH), 7.74
(s, 1 H, ArH), 13.09 (br s, 1 H, OH).
13C NMR (125 MHz, CDCl3): d = 28.2 (2 C), 33.2, 33.4, 40.2, 50.9,
113.6, 126.7, 128.0, 128.3, 129.6, 131.4, 134.5, 135.6, 136.3, 152.7,
165.6, 194.0.
A mixture of a Morita–Baylis–Hillman adduct acetate 1 (1 mmol),
a cyclic b-diketone 2 (1.2 mmol) and Et3N (1.2 mmol) was stirred
at 90 °C for the indicated time (Tables 1 and 2). Then, NH4OAc (3
mmol) or a primary amine 5 (3 mmol) was added to the mixture, and
the reaction mixture was further stirred for the given time (Tables 1
and 2). The mixture was cooled, the reaction was quenched with
EtOH–H2O (4:1; 5 mL) and the mixture was stirred at 0 °C for 3 h.
Finally, the product 4 or 6 was isolated by simple filtration and
washed with cooled EtOH.
MS (ESI): m/z (%) = 316 (100) [M+ + 1].
Anal. Calcd for C18H18ClNO2: C, 68.46; H, 5.75; N, 4.44. Found: C,
68.14; H, 5.97; N, 4.56.
3-Benzyl-2-hydroxy-7,7-dimethyl-7,8-dihydroquinolin-5(6H)-
one (4a)
White solid; mp 218.6–220.2 °C; Rf = 0.30 (hexane–EtOAc, 1:1).
IR (KBr): 3423, 3134, 1683, 1630, 1397, 1216 cm–1.
3-(2-Chloro-6-fluorobenzyl)-2-hydroxy-7,7-dimethyl-7,8-dihy-
droquinolin-5(6H)-one (4d)
White solid; mp 281.8–284.1 °C; Rf = 0.25 (hexane–EtOAc, 1:1).
IR (KBr): 3420, 3125, 1673, 1636, 1401, 1210 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.14 (s, 6 H, CH3), 2.39 (s, 2 H,
CH2), 2.81 (s, 2 H, CH2), 4.03 (s, 2 H, CH2), 6.99–7.03 (m, 1 H,
ArH), 7.18–7.23 (m, 2 H, ArH), 7.56 (s, 1 H, ArH), 13.16 (br s, 1 H,
OH).
13C NMR (125 MHz, CDCl3): d = 26.7 (d, J = 3.8 Hz), 28.2 (2 C),
33.2, 40.2, 51.0, 113.6, 114.1 (d, J = 22.5 Hz), 124.4 (d, J = 17.5
1H NMR (500 MHz, CDCl3): d = 1.11 (s, 6 H, CH3), 2.39 (s, 2 H,
CH2), 2.70 (s, 2 H, CH2), 3.84 (s, 2 H, CH2), 7.18–7.22 (m, 1 H,
ArH), 7.25–7.30 (m, 4 H, ArH), 7.85 (s, 1 H, ArH), 13.11 (br s, 1 H,
OH).
13C NMR (125 MHz, CDCl3): d = 28.3 (2 C), 33.2, 36.1, 40.2, 50.9,
113.7, 126.3, 128.4 (2 C), 129.0 (2 C), 130.1, 135.5, 139.1, 152.7,
165.8, 194.1.
MS (ESI): m/z (%) = 282 (100) [M+ + 1].
Synthesis 2008, No. 16, 2561–2568 © Thieme Stuttgart · New York

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2-Hydroxy-7,8-dihydroquinolin-5(6H)-ones and 7,8-Dihydroquinoline-2,5(1H,6H)-diones
2565
Hz), 125.4 (d, J = 2.5 Hz), 127.1, 128.6 (d, J = 10.0 Hz), 134.6,
135.9 (d, J = 7.5 Hz), 152.6, 161.9 (d, J = 247.5 Hz), 165.5, 193.9.
MS (ESI): m/z (%) = 334 (100) [M+ + 1].
MS (ESI): m/z (%) = 308 (100) [M+ – 1].
Anal. Calcd for C20H23NO2: C, 77.64; H, 7.49; N, 4.53. Found: C,
77.53; H, 7.49; N, 4.51.
Anal. Calcd for C18H17ClFNO2: C, 64.77; H, 5.13; N, 4.20. Found:
C, 64.54; H, 5.13; N, 4.28.
3-(3,4-Dimethylbenzyl)-7,7-dimethyl-7,8-dihydroquinoline-
2,5(1H,6H)-dione (4h¢)
White solid; mp 196.8–198.0 °C; Rf = 0.35 (hexanes–EtOAc, 1:1).
3-(4-Fluorobenzyl)-2-hydroxy-7,7-dimethyl-7,8-dihydroquino-
lin-5(6H)-one (4e)
IR (KBr): 3423, 3134, 1635, 1528, 1401, 1233 cm–1.
White solid; mp 201.7–203.0 °C; Rf = 0.30 (hexane–EtOAc, 1:1).
IR (KBr): 3423, 3137, 1684, 1632, 1611, 1508, 1398, 1217 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.12 (s, 6 H, CH3), 2.30 (s, 6 H,
CH3), 2.31 (s, 2 H, CH2), 2.36 (s, 2 H, CH2), 3.71 (s, 2 H, CH2), 7.22
(d, J = 7.5 Hz, 1 H, ArH), 7.31 (dd, J = 8.5, 8.0 Hz, 2 H, ArH), 7.85
(s, 1 H, ArH), 8.24 (s, 1 H, NH).
13C NMR (125 MHz, CDCl3): d = 19.8, 19.9, 24.8, 28.3 (2 C), 32.9,
41.1, 50.5, 109.5, 124.2, 128.1, 130.0, 132.3, 132.6, 136.9, 138.6,
139.6, 148.3, 166.3, 195.8.
1H NMR (500 MHz, CDCl3): d = 1.13 (s, 6 H, CH3), 2.40 (s, 2 H,
CH2), 2.70 (s, 2 H, CH2), 3.81 (s, 2 H, CH2), 6.94–6.98 (m, 2 H,
ArH), 7.22–7.27 (m, 2 H, ArH), 7.84 (s, 1 H, ArH), 13.04 (br s, 1 H,
OH).
13C NMR (125 MHz, CDCl3): d = 28.2 (2 C), 33.2, 35.4, 40.2, 50.9,
113.7, 115.1, 115.3, 130.2 (d, J = 82.5 Hz), 130.4, 134.7, 134.8,
135.5, 152.8, 161.5 (d, J = 224.5 Hz), 165.7, 194.0.
MS (ESI): m/z (%) = 308 (100) [M+ – 1].
Anal. Calcd for C20H23NO2: C, 77.64; H, 7.49; N, 4.53. Found: C,
77.49; H, 7.58; N, 4.53.
MS (EI): m/z (%) = 299 (100) [M+].
Anal. Calcd for C18H18FNO2: C, 72.22; H, 6.06; N, 4.68. Found: C,
72.01; H, 6.04; N, 4.78.
3-(1,3-Benzodioxol-5-ylmethyl)-2-hydroxy-7,7-dimethyl-7,8-di-
hydroquinolin-5(6H)-one (4i)
White solid; mp 206.8–208.2 °C; Rf = 0.30 (hexanes–EtOAc, 1:1).
IR (KBr): 3413, 3138, 2961, 1636, 1401, 1249 cm–1.
3-(Furan-2-ylmethyl)-2-hydroxy-7,7-dimethyl-7,8-dihydro-
quinolin-5(6H)-one (4f)
White solid; mp 216.9–218.7 °C; Rf = 0.35 (hexane–EtOAc, 1:1).
IR (KBr): 3422, 3129, 1671, 1637, 1400, 1206 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.13 (s, 6 H, CH3), 2.40 (s, 2 H,
CH2), 2.75 (s, 2 H, CH2), 3.89 (s, 2 H, CH2), 6.13 (d, J = 3.0 Hz, 1
H, ArH), 6.30–6.35 (m, 1 H, ArH), 7.33 (d, J = 1.0 Hz, 1 H, ArH),
7.86 (s, 1 H, ArH), 12.99 (br s, 1 H, OH).
1H NMR (500 MHz, CDCl3): d = 1.13 (s, 6 H, CH3), 2.40 (s, 2 H,
CH2), 2.74 (s, 2 H, CH2), 3.75 (s, 2 H, CH2), 5.91 (s, 2 H, CH2),
6.71–6.75 (m, 2 H, ArH), 6.80 (s, 1 H, ArH), 7.82 (s, 1 H, ArH),
12.99 (br s, 1 H, OH).
13C NMR (125 MHz, CDCl3): d = 28.2 (2 C), 33.2, 35.7, 40.3, 51.0,
100.8, 108.2, 109.6, 113.7, 122.0, 130.3, 132.8, 135.3, 146.1, 147.6,
152.6, 165.7, 194.1.
13C NMR (125 MHz, CDCl3): d = 28.2 (2 C), 28.3, 33.2, 40.3, 50.9,
106.8, 110.3, 113.7, 127.1, 135.8, 141.6, 152.2, 152.9, 165.5, 193.9.
MS (ESI): m/z (%) = 324 (100) [M+ – 1].
MS (ESI): m/z (%) = 272 (100) [M+ + 1].
Anal. Calcd for C19H19NO4: C, 70.14; H, 5.89; N, 4.31. Found: C,
69.97; H, 6.04; N, 4.37.
Anal. Calcd for C16H17NO3: C, 70.83; H, 6.32; N, 5.16. Found: C,
70.79; H, 6.33; N, 5.14.
2-Hydroxy-3-(3-methoxybenzyl)-7,7-dimethyl-7,8-dihydro-
quinolin-5(6H)-one (4j)
White solid; mp 158.6–159.6 °C; Rf = 0.30 (hexanes–EtOAc, 1:1).
IR (KBr): 3425, 3137, 3025, 2958, 1684, 1634, 1397, 1217 cm–1.
2-Hydroxy-7,7-dimethyl-3-(thien-2-ylmethyl)-7,8-dihydroquin-
olin-5(6H)-one (4g)
White solid; mp 227.2–229.1 °C; Rf = 0.25 (hexane–EtOAc, 1:1).
IR (KBr): 3414, 3135, 1647, 1617, 1400, 1218 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.12 (s, 6 H, CH3), 2.39 (s, 2 H,
CH2), 2.72 (s, 2 H, CH2), 3.77 (s, 3 H, OCH3), 3.82 (s, 2 H, CH2),
6.74 (d, J = 8.0 Hz, 1 H, ArH), 6.87 (dd, J = 10.5, 8.0 Hz, 2 H, ArH),
7.20 (t, J = 8.0 Hz, 1 H, ArH), 7.85 (s, 1 H, ArH), 13.05 (br s, 1 H,
OH).
13C NMR (125 MHz, CDCl3): d = 28.2 (2 C), 33.2, 36.1, 40.2, 51.0,
55.1, 111.2, 113.7, 115.3, 121.4, 129.4, 130.0, 135.6, 140.7, 152.7,
159.6, 165.8, 194.1.
1H NMR (500 MHz, CDCl3): d = 1.13 (s, 6 H, CH3), 2.41 (s, 2 H,
CH2), 2.79 (s, 2 H, CH2), 4.05 (s, 2 H, CH2), 6.91–6.94 (m, 2 H,
ArH), 7.13 (d, J = 4.5 Hz, 1 H, ArH), 7.92 (s, 1 H, ArH), 13.10 (br
s, 1 H, OH).
13C NMR (125 MHz, CDCl3): d = 28.3 (2 C), 30.1, 33.2, 40.3, 51.0,
113.8, 124.0, 125.8, 126.9, 129.4, 135.6, 141.3, 153.0, 165.5, 194.0.
MS (ESI): m/z (%) = 286 (100) [M+ – 1].
MS (ESI): m/z (%) = 310 (100) [M+ – 1].
Anal. Calcd for C16H17NO2S: C, 66.87; H, 5.96; N, 4.87. Found: C,
66.52; H, 5.84; N, 4.68.
Anal. Calcd for C19H21NO3: C, 73.29; H, 6.80; N, 4.50. Found: C,
73.36; H, 6.78; N, 4.41.
3-(3,4-Dimethylbenzyl)-2-hydroxy-7,7-dimethyl-7,8-dihydro-
quinolin-5(6H)-one (4h)
White solid; mp 216.0–218.5 °C; Rf = 0.30 (hexane–EtOAc, 1:1).
IR (KBr): 3433, 3133, 1637, 1595, 1400, 1236 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.11 (s, 6 H, CH3), 2.21 (s, 6 H,
CH3), 2.39 (s, 2 H, CH2), 2.73 (s, 2 H, CH2), 3.77 (s, 2 H, CH2), 7.04
(s, 3 H, ArH), 7.82 (s, 1 H, ArH), 12.92 (br s, 1 H, OH).
13C NMR (125 MHz, CDCl3): d = 19.4, 19.8, 28.2 (2 C), 33.2, 35.5,
40.3, 51.0, 113.7, 126.5, 129.7, 130.3, 130.6, 134.5, 135.3, 136.4,
136.5, 152.5, 165.7, 194.1.
3-(4-Fluorobenzyl)-2-hydroxy-7,8-dihydroquinolin-5(6H)-one
(4k)
White solid; mp 208.0–210.0 °C; Rf = 0.25 (hexanes–EtOAc, 1:1).
IR (KBr): 3413, 3137, 1675, 1639, 1401, 1192 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.13 (t, J = 6.5 Hz, 2 H, CH2), 2.54
(t, J = 6.5 Hz, 2 H, CH2), 2.82 (t, J = 6.5 Hz, 2 H, CH2), 3.79 (s, 2
H, CH2), 6.93–6.97 (m, 2 H, ArH), 7.21–7.26 (m, 2 H, ArH), 7.84
(s, 1 H, ArH), 12.85 (br s, 1 H, OH).
Synthesis 2008, No. 16, 2561–2568 © Thieme Stuttgart · New York

2566
W. Zhong et al.
PAPER
13C NMR (125 MHz, CDCl3): d = 21.4, 26.8, 35.3, 37.2, 114.7,
115.1, 115.3, 130.3 (d, J = 27.5 Hz), 130.5, 134.7, 134.7, 135.8,
154.1, 160.6, 163.9 (d, J = 343.8 Hz), 194.1.
crude product. Column chromatography (silica gel, hexane–EtOAc,
4:1→ 6:1 gradient elution) gave the desired product 4o in 55% iso-
lated yield (144 mg).
MS (ESI): m/z (%) = 272 (100) [M+ + 1].
White solid; mp 142.5–143.3 °C; Rf = 0.40 (hexanes–EtOAc, 2:1).
Anal. Calcd for C16H14FNO2: C, 70.84; H, 5.20; N, 5.16. Found: C,
70.66; H, 5.22; N, 5.32.
IR (KBr): 3238, 3161, 2956, 2930, 1692, 1613, 1390, 1239 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.92 (t, J = 7.0 Hz, 3 H, CH3), 1.11
(s, 6 H, CH3), 1.33–1.41 (m, 2 H, CH2), 1.45–1.51 (m, 2 H, CH2),
2.19–2.33 (m, 2 H, CH2), 2.34 (s, 2 H, CH2), 2.35 (s, 2 H, CH2),
3.33–3.34 (m, 2 H, CH2), 7.01–7.05 (m, 1 H, ArH), 8.65 (s, 1 H,
NH).
13C NMR (125 MHz, CDCl3): d = 13.9, 22.5, 22.6, 28.3, 28.4 (2 C),
30.2, 32.9, 40.9, 50.5, 109.6, 125.4, 144.6, 149.1, 165.8, 196.2.
2-Hydroxy-3-(3-nitrobenzyl)-7,8-dihydroquinolin-5(6H)-one
(4l)
White solid; mp 247.4–249.5 °C; Rf = 0.20 (hexanes–EtOAc, 1:1).
IR (KBr): 3410, 3134, 1684, 1635, 1401, 1233 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.19 (t, J = 6.5 Hz, 2 H, CH2), 2.57
(t, J = 6.5 Hz, 2 H, CH2), 2.90 (t, J = 6.5 Hz, 2 H, CH2), 3.91 (s, 2
H, CH2), 7.43 (t, J = 7.5 Hz, 1 H, ArH), 7.60 (d, J = 7.5 Hz, 1 H,
ArH), 7.97 (s, 1 H, ArH), 8.04–8.27 (m, 1 H, ArH), 8.28 (s, 1 H,
ArH), 13.12 (br s, 1 H, OH).
MS (ESI): m/z (%) = 262 (100) [M+ + 1].
Anal. Calcd for C16H23NO2: C, 73.53; H, 8.87; N, 5.36. Found: C,
73.44; H, 8.98; N, 5.47.
13C NMR (125 MHz, CDCl3): d = 21.4, 26.9, 36.2, 37.1, 114.7,
121.6, 124.3, 128.7, 129.2, 135.1, 136.3, 141.3, 148.2, 154.9, 165.2,
194.1.
1-n-Butyl-3-(4-fluorobenzyl)-7,7-dimethyl-7,8-dihydroquino-
line-2,5(1H,6H)-dione (6a)
A mixture of the Morita–Baylis–Hillman adduct acetate 1 (R1 =
4-FC6H4, R2 = Me; 1 mmol), 5,5-dimethylcyclohexane-1,3-dione
(2a; 1.2 mmol) and Et3N (1.2 mmol) was stirred at 90 °C until TLC
monitoring indicated complete consumption of the Morita–Baylis–
Hillman adduct acetate. Then, n-BuNH2 (3 mmol) was added to the
reaction mixture which was further stirred at 70 °C for 3 h (the
progress of the reaction was monitored by TLC). Brine was added
and the suspension was extracted twice with EtOAc. The organic
phase was dried over Na2SO4, then concentrated to give the crude
product. Column chromatography (silica gel, hexane–EtOAc, 2:1→
4:1 gradient elution) gave the desired product 6a in 85% isolated
yield (302 mg).
MS (ESI): m/z (%) = 297 (100) [M+ – 1].
Anal. Calcd for C16H14N2O4: C, 64.42; H, 4.73; N, 9.39. Found: C,
64.12; H, 4.93; N, 9.40.
3-Benzyl-2-hydroxy-7,8-dihydroquinolin-5(6H)-one (4m)
White solid; mp 205.8–206.9 °C; Rf = 0.30 (hexanes–EtOAc, 1:1).
IR (KBr): 3415, 3136, 1639, 1606, 1401, 1224 cm–1.
1H NMR (500 MHz, CDCl3): d = 2.12 (t, J = 6.5 Hz, 2 H, CH2), 2.53
(t, J = 6.5 Hz, 2 H, CH2), 2.81 (t, J = 6.5 Hz, 2 H, CH2), 3.83 (s, 2
H, CH2), 7.18–7.21 (m, 1 H, ArH), 7.24–7.28 (m, 4 H, ArH), 7.85
(s, 1 H, ArH), 12.94 (br s, 1 H, OH).
Viscous yellowish oil; Rf = 0.55 (hexane–EtOAc, 1:1).
13C NMR (125 MHz, CDCl3): d = 21.5, 26.8, 36.0, 37.2, 114.7,
126.4, 128.4 (2 C), 129.1 (2 C), 130.4, 135.8, 139.1, 154.1, 165.4,
194.2.
IR (neat): 3041, 2960, 2872, 1644, 1423, 1220 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.99 (t, J = 7.5 Hz, 3 H, CH3), 1.14
(s, 6 H, CH3), 1.41–1.49 (m, 2 H, CH2), 1.61–1.68 (m, 2 H, CH2),
2.39 (s, 2 H, CH2), 2.77 (s, 2 H, CH2), 3.80 (s, 2 H, CH2), 4.04 (t,
J = 7.5 Hz, 2 H, CH2), 6.94–6.98 (m, 2 H, ArH), 7.23–7.28 (m, 2 H,
ArH), 7.75 (s, 1 H, ArH).
MS (ESI): m/z (%) = 252 (100) [M+ – 1].
Anal. Calcd for C16H15NO2: C, 75.87; H, 5.97; N, 5.53. Found: C,
75.99; H, 6.12; N, 5.51.
13C NMR (125 MHz, CDCl3): d = 13.7, 19.3 (d, J = 231.3 Hz), 28.5,
30.8, 32.9, 36.1, 40.7, 44.4, 49.9, 58.4, 113.4, 115.1, 115.3, 129.8,
130.5 (d, J = 8.8 Hz), 132.9, 134.7, 134.8, 152.8, 160.6, 162.8 (d,
J = 66.2 Hz), 194.2.
2-Hydroxy-3-(3-methoxybenzyl)-7,8-dihydroquinolin-5(6H)-
one (4n)
White solid; mp 175.3–176.6 °C; Rf = 0.15 (hexanes–EtOAc, 1:1).
IR (KBr): 3430, 3131, 1640, 1401, 1452, 1228 cm–1.
MS (ESI): m/z (%) = 356 (100) [M+ + 1].
1H NMR (500 MHz, CDCl3): d = 2.12 (t, J = 6.5 Hz, 2 H, CH2), 2.53
(t, J = 6.5 Hz, 2 H, CH2), 2.82 (t, J = 6.5 Hz, 2 H, CH2), 3.77 (s, 3
H, OCH3), 3.80 (s, 2 H, CH2), 6.72–6.75 (m, 1 H, ArH), 6.83–6.86
(m, 2 H, ArH), 7.20 (t, J = 8.0 Hz, 1 H, ArH), 7.86 (s, 1 H, ArH),
12.95 (br s, 1 H, OH).
Anal. Calcd for C22H26FNO2: C, 74.34; H, 7.37; N, 3.94. Found: C,
74.54; H, 7.17; N, 3.94.
7,7-Dimethyl-3-(3-nitrobenzyl)-1-phenyl-7,8-dihydroquinoline-
2,5(1H,6H)-dione (6b)
13C NMR (125 MHz, CDCl3): d = 21.5, 26.8, 36.0, 37.2, 55.2,
111.3, 114.7, 115.2, 121.5, 129.4, 130.2, 135.9, 140.7, 154.2, 159.6,
165.4, 194.2.
White solid; mp 175.0–177.3 °C; Rf = 0.35 (hexanes–EtOAc, 1:1).
IR (KBr): 3132, 1651, 1518, 1402, 1209 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.01 (s, 6 H, CH3), 2.29 (s, 2 H,
CH2), 2.38 (s, 2 H, CH2), 3.94 (s, 2 H, CH2), 7.16 (t, J = 7.5 Hz, 2
H, ArH), 7.44 (t, J = 8.0 Hz, 1 H, ArH), 7.49–7.52 (m, 1 H, ArH),
7.54–7.57 (m, 2 H, ArH), 7.68 (d, J = 4.0 Hz, 1 H, ArH), 7.93 (s, 1
H, ArH), 8.05–8.12 (m, 1 H, ArH), 8.13 (s, 1 H, ArH).
MS (ESI): m/z (%) = 282 (100) [M+ – 1].
Anal. Calcd for C17H17NO3: C, 72.07; H, 6.05; N, 4.94. Found: C,
71.83; H, 6.26; N, 5.05.
13C NMR (125 MHz, CDCl3): d = 28.2 (2 C), 33.0, 36.7, 42.2, 50.1,
113.2, 121.6, 123.8, 127.6 (2 C), 129.3 (2 C), 129.4, 130.2 (2 C),
134.1, 135.6, 137.5, 141.0, 148.3, 154.2, 163.3, 194.1.
7,7-Dimethyl-3-pentyl-7,8-dihydroquinoline-2,5(1H,6H)-dione
(4o)
A mixture of Morita–Baylis–Hillman adduct acetate 1o (1 mmol),
5,5-dimethylcyclohexane-1,3-dione (2a; 1.2 mmol), Et3N (1.2
mmol) and NH4OAc (3 mmol) was stirred at 90 °C until TLC mon-
itoring indicated complete consumption of adduct 1o. Brine was
added and the suspension was extracted twice with EtOAc. The or-
ganic phase was dried over Na2SO4, then concentrated to give the
MS (ESI): m/z (%) = 403 (100) [M+ + 1].
Anal. Calcd for C24H22N2O4: C, 71.63; H, 5.51; N, 6.96. Found: C,
71.46; H, 5.52; N, 6.84.
Synthesis 2008, No. 16, 2561–2568 © Thieme Stuttgart · New York

PAPER
2-Hydroxy-7,8-dihydroquinolin-5(6H)-ones and 7,8-Dihydroquinoline-2,5(1H,6H)-diones
2567
7,7-Dimethyl-3-(3-nitrobenzyl)-1-p-tolyl-7,8-dihydroquinoline-
2,5(1H,6H)-dione (6c)
White solid; mp 187.4–189.1 °C; Rf = 0.35 (hexane–EtOAc, 1:1).
IR (KBr): 3128, 1649, 1618, 1403, 1209 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.01 (s, 6 H, CH3), 2.32 (s, 2 H,
CH2), 2.38 (s, 2 H, CH2), 2.42 (s, 3 H, CH3), 3.93 (s, 2 H, CH2), 7.03
(d, J = 7.5 Hz, 2 H, ArH), 7.34 (d, J = 7.5 Hz, 2 H, ArH), 7.43 (t,
J = 7.5 Hz, 1 H, ArH), 7.68 (d, J = 7.0 Hz, 1 H, ArH), 7.93 (s, 1 H,
ArH), 8.05 (d, J = 7.5 Hz, 1 H, ArH), 8.13 (s, 1 H, ArH).
13C NMR (125 MHz, CDCl3): d = 21.2, 28.2 (2 C), 33.0, 36.7, 42.2,
50.1, 113.2, 121.6, 123.9, 127.3 (2 C), 129.2, 129.3, 130.8 (2 C),
134.0, 134.8, 135.7, 139.5, 141.1, 148.3, 154.5, 163.5, 194.2.
13C NMR (125 MHz, CDCl3): d = 28.2 (d, J = 3.8 Hz, 2 C), 33.1,
36.7, 42.2, 50.2, 113.5, 117.7, 117.9, 118.7, 118.9, 121.7, 123.8,
124.7, 129.4, 129.5, 133.4, 134.4, 135.6, 140.7, 149.1 (d, J = 182.5
Hz), 152.8 (d, J = 208.8 Hz), 163.1, 193.8.
MS (ESI): m/z (%) = 437 (100) [M+ – 1].
Anal. Calcd for C24H20F2N2O4: C, 65.75; H, 4.60; N, 6.39. Found:
C, 65.59; H, 4.71; N, 6.46.
7,7-Dimethyl-3-(3-nitrobenzyl)-1-(4-phenylthiazol-2-yl)-7,8-di-
hydroquinoline-2,5(1H,6H)-dione (6g)
White solid; mp 169.4–170.5 °C; Rf = 0.35 (hexane–EtOAc, 1:1).
IR (KBr): 3129, 1662, 1560, 1532, 1401, 1344 cm–1.
MS (ESI): m/z (%) = 415 (100) [M+ – 1].
1H NMR (500 MHz, CDCl3): d = 1.05 (s, 6 H, CH3), 2.42 (s, 2 H,
CH2), 2.53 (s, 2 H, CH2), 3.96 (s, 2 H, CH2), 7.39 (t, J = 1.0 Hz, 1
H, ArH), 7.43–7.48 (m, 3 H, ArH), 7.67 (d, J = 8.0 Hz, 1 H, ArH),
7.72 (s, 1 H, ArH), 7.86–7.88 (m, 2 H, ArH), 7.92 (s, 1 H, ArH),
8.07–8.15 (m, 1 H, ArH), 8.16 (s, 1 H, ArH).
13C NMR (125 MHz, CDCl3): d = 28.3 (2 C), 33.0, 36.5, 41.4, 50.1,
114.0, 115.9, 121.8, 124.0, 126.3 (2 C), 128.9 (2 C), 129.0, 129.4,
129.7, 133.4, 134.7, 135.6, 140.5, 148.4, 153.7, 154.2, 156.4, 163.2,
194.0.
Anal. Calcd for C25H24N2O4: C, 72.10; H, 5.81; N, 6.73. Found: C,
72.26; H, 5.75; N, 6.60.
1-(4-Methoxyphenyl)-7,7-dimethyl-3-(3-nitrobenzyl)-7,8-di-
hydroquinoline-2,5(1H,6H)-dione (6d)
White solid; mp 153.4–154.7 °C; Rf = 0.35 (hexane–EtOAc, 1:1).
IR (KBr): 3133, 2651, 2574, 1732, 1401, 1223 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.02 (s, 6 H, CH3), 2.33 (s, 2 H,
CH2), 2.38 (s, 2 H, CH2), 3.87 (s, 3 H, CH3), 3.94 (s, 2 H, CH2), 7.05
(d, J = 9.0 Hz, 4 H, ArH), 7.43 (t, J = 7.5 Hz, 1 H, ArH), 7.68 (d,
J = 7.5 Hz, 1 H, ArH), 7.92 (s, 1 H, ArH), 8.06 (d, J = 8.5 Hz, 1 H,
ArH), 8.13 (s, 1 H, ArH).
MS (ESI): m/z (%) = 484 (100) [M+ – 1].
Anal. Calcd for C27H23N3O4S: C, 66.79; H, 4.77; N, 8.65. Found: C,
66.54; H, 4.86; N, 8.67.
13C NMR (125 MHz, CDCl3): d = 28.3 (2 C), 33.0, 36.8, 42.4, 50.1,
55.6, 113.3, 115.4 (2 C), 121.6, 123.9, 128.7 (2 C), 129.2, 129.3,
130.0, 134.0, 135.7, 141.1, 148.4, 154.7, 160.0, 163.6, 194.2.
Acknowledgment
We thank the National Natural Science Foundation of China
(20676123) for financial support.
MS (ESI): m/z (%) = 431 (100) [M+ – 1].
Anal. Calcd for C25H24N2O5: C, 69.43; H, 5.59; N, 6.48. Found: C,
69.27; H, 5.68; N, 6.61.
References
(1) (a) Raffaella, B.; Michele, F.; Paola, F.; Luisa, M. Quant.
Struct.-Act. Relat. 1997, 16, 201. (b) El-Sheikh, M. I.;
Cook, J. M. J. Org. Chem. 1980, 45, 2585.
1-(4-Chlorophenyl)-7,7-dimethyl-3-(3-nitrobenzyl)-7,8-di-
hydroquinoline-2,5(1H,6H)-dione (6e)
White solid; mp 206.7–209.3 °C; Rf = 0.35 (hexane–EtOAc, 1:1).
(2) (a) Carlier, P. R.; Du, D. M.; Han, Y. F.; Liu, J.; Perola, E.;
Williams, I. D.; Pang, Y. P. Angew. Chem. Int. Ed. 2000, 39,
1775. (b) Rivikin, A.; Adams, B. Tetrahedron Lett. 2006,
47, 2395. (c) Christos, A. M.; Alexandros, L. Z.; Olga, I. M.
J. Org. Chem. 2003, 68, 4567. (d) Pita, B.; Masaguer, C. F.;
Raviña, E. Tetrahedron Lett. 2002, 43, 7929. (e) Lee, Y. R.;
Kweon, H. I.; Koh, W. S.; Min, K. R.; Kim, Y.; Lee, S. H.
Synthesis 2001, 1851.
IR (KBr): 3132, 2573, 1735, 1637, 1401, 1223 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.03 (s, 6 H, CH3), 2.29 (s, 2 H,
CH2), 2.39 (s, 2 H, CH2), 3.94 (s, 2 H, CH2), 7.11 (d, J = 8.0 Hz, 2
H, ArH), 7.44 (t, J = 7.5 Hz, 1 H, ArH), 7.53 (d, J = 8.0 Hz, 2 H,
ArH), 7.67 (d, J = 7.0 Hz, 1 H, ArH), 7.93 (s, 1 H, ArH), 8.06 (d,
J = 8.0 Hz, 1 H, ArH), 8.12 (s, 1 H, ArH).
13C NMR (125 MHz, CDCl3): d = 28.3 (2 C), 33.1, 36.7, 42.3, 50.1,
113.5, 121.7, 123.8, 129.2 (2 C), 129.3, 129.4, 130.5 (2 C), 134.3,
135.6, 135.7, 135.9, 140.9, 148.4, 153.8, 163.2, 194.0.
(3) Anderson, W. K.; Dean, D. C.; Endo, T. J. Med. Chem. 1990,
33, 1667.
(4) Pita, B.; Masaguer, C. F.; Raviña, E. Tetrahedron Lett. 2000,
41, 9829.
MS (ESI): m/z (%) = 435 (100) [M+ – 1].
(5) Li, Q.; Mitscher, L. A.; Shen, L. L. Med. Res. Rev. 2000, 20,
231.
Anal. Calcd for C24H21ClN2O4: C, 65.98; H, 4.84; N, 6.41. Found:
C, 65.87; H, 4.95; N, 6.41.
(6) (a) Gorobets, N. Y.; Yousefi, B. H.; Belaj, F.; Kappe, C. O.
Tetrahedron 2004, 60, 8633. (b) Dorigo, P.; Gaion, R. M.;
Belluco, P.; Fraccarollo, D.; Maragno, I.; Bombierij, G.;
Benetollo, F.; Mosti, L.; Orsinil, F. J. Med. Chem. 1993, 36,
2475.
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2000, 41, 7751.
(8) (a) Morita, K.; Suzuki, Z.; Hirose, H. Bull. Chem. Soc. Jpn.
1968, 41, 2815. (b) Basavaiah, D.; Rao, P. D.; Hyma, R. S.
Tetrahedron 1996, 52, 8001. (c) Basavaiah, D.; Rao, A. J.;
Satyanarayana, T. Chem. Rev. 2003, 103, 811.
1-(3,4-Difluorophenyl)-7,7-dimethyl-3-(3-nitrobenzyl)-7,8-di-
hydroquinoline-2,5(1H,6H)-dione (6f)
White solid; mp 195.1–197.0 °C; Rf = 0.30 (hexane–EtOAc, 1:1).
IR (KBr): 3131, 1654, 1401, 1271 cm–1.
1H NMR (500 MHz, CDCl3): d = 1.04 (s, 6 H, CH3), 2.31 (s, 2 H,
CH2), 2.39 (s, 2 H, CH2), 3.93 (s, 2 H, CH2), 6.94 (d, J = 8.0 Hz, 1
H, ArH), 7.04 (t, J = 7.5 Hz, 1 H, ArH), 7.36 (d, J = 8.0 Hz, 1 H,
ArH), 7.45 (t, J = 8.0 Hz, 1 H, ArH), 7.67 (d, J = 7.5 Hz, 1 H, ArH),
7.93 (s, 1 H, ArH), 8.07 (d, J = 8.0 Hz, 1 H, ArH), 8.11 (s, 1 H,
ArH).
Synthesis 2008, No. 16, 2561–2568 © Thieme Stuttgart · New York

2568
W. Zhong et al.
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