First construction of 12H-thiochromeno[2,3-b]quinolines and 5H-benzo[7,8]thiocino-[2,3-b]quinolines via intramolecular Friedel-Crafts reaction of Morita-Baylis-Hillman adducts

Article abstract of DOI:10.1016/j.tet.2011.03.039

An acid-promoted intramolecular Friedel-Crafts reaction of the Morita-Baylis-Hillman adducts 3 derived from 2-arylthioquinolin-3-carbaldehydes 2 was investigated. Interestingly, promoted by sulfuric acid, the substrates with electron-donating groups on the aromatic ring gave six-membered fused-ring 12H-thiochromeno[2,3-b]quinolines 4 with good yields, while those with electron-withdrawing groups afforded eight-membered fused-ring 5H-benzo[7,8]thiocino[2,3-b]quinolines 5 in moderate yields. Using triflic acid instead of sulfuric acid, only products 4 could be obtained under the similar condition.

Full text of DOI:10.1016/j.tet.2011.03.039

Tetrahedron 67 (2011) 3509e3518
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
First construction of 12H-thiochromeno[2,3-b]quinolines and 5H-benzo[7,8]
thiocino-[2,3-b]quinolines via intramolecular FriedeleCrafts reaction of
MoritaeBayliseHillman adducts
*
Weihui Zhong , Wang Ma, Yanbin Liu
Key Laboratory of Pharmaceutical Engineering of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou 310014, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An acid-promoted intramolecular FriedeleCrafts reaction of the MoritaeBayliseHillman adducts 3 de-
rived from 2-arylthioquinolin-3-carbaldehydes 2 was investigated. Interestingly, promoted by sulfuric
acid, the substrates with electron-donating groups on the aromatic ring gave six-membered fused-ring
12H-thiochromeno[2,3-b]quinolines 4 with good yields, while those with electron-withdrawing groups
afforded eight-membered fused-ring 5H-benzo[7,8]thiocino[2,3-b]quinolines 5 in moderate yields. Using
triflic acid instead of sulfuric acid, only products 4 could be obtained under the similar condition.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 26 November 2010
Received in revised form 27 February 2011
Accepted 14 March 2011
Available online 21 March 2011
Keywords:
MoritaeBayliseHillman adduct
FriedeleCrafts reaction
Acid-promoted
12H-thiochromeno[2,3-b]quinoline
5H-Benzo[7,8]thiocino[2,3-b]quinoline
1. Introduction
numerous elegant synthetic methods have been developed, it still
need to explore new and efficient synthetic routes for the synthesis
Quinolines and their analogues, play important roles in the het-
erocycles chemistry due totheir various biological acitivities, such as
antimalarials,1 bactericidal,2 antitumor,3 anti-inflammatory,4 anti-
proliferative,5 antiviral,6 and etc. Quinoline containing fused-rings,
of this class of compounds, particularly those with general applica-
bility in achieving more flexible substitution pattern.9
The MoritaeBayliseHillman (MBH) reaction is a useful carbone
carbon bond formation reaction from aldehydes and activated
alkenes, which is a one-pot, atom economical reaction and provides
multi-functionalized adducts catalyzed by a tertiary amine.10 These
MBH adducts and their derivatives were widely employed for the
synthesis of a variety of useful heterocyclic compounds by us11 and
other groups.12
such as 3,4-dihydro-2H-thiopyrano[2,3-b]quinoline
I showed
metabotropic glutamate receptor antagonistic activity, in particular
mGlu 1 receptor activity,7 and 2H-thiopyrano[2,3-b]quinoline-2-
carboxylic acid II could be used as a strong antioxidant to protect
oxidative DNA damage from harmful free radicals (Fig.1).8 Although
Recently, Junjappa et al. reported the synthesis of benzo-
thiopyrano[2,3-b]quinoline derivatives by treatment of 3-(o-
bromobenzoyl)quinoline with Bu3SnH/AIBN.13 Ramesh demon-
strated thiopyanoquinoline derivatives could be prepared
through imino DielseAlder reaction using silica gel impregnated
with indium trichloride as
a
catalyst.14 To the best of our
knowledge, the preparation of 2H-thiochromeno[2,3-b]quinoline
derivatives from MBH adducts has not been reported. With our
ongoing interest in the synthesis of heterocycles from MBH
adducts, we herein report the first construction of 12H-
thiochromeno[2,3-b]quinolines and 5H-benzo[7,8]thiocino[2,3-b]
quinolines via intramolecular FriedeleCrafts reaction of MBH
adducts (Fig. 2).
Fig. 1. Representative biologically active molecules containing 2H-thiopyrano[2,3-b]
quinoline ring systems.
* Corresponding author. Tel./fax: þ86 57188320752; e-mail address: pharmlab@
zjut.edu.cn (W. Zhong).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.039

3510
W. Zhong et al. / Tetrahedron 67 (2011) 3509e3518
Table 2
Synthesis of MBH adducts 3 from 2-arylthioquinoline-3-carbaldehydes 2a
OH
EWG
CHO
S
EWG
R1
R1
N
MBH reaction
N
S
R2
R2
2
3
Entry
R1
R2
EWG
Time (d)
Products
Yieldb (%)
1
2
3
4
5
6
7
8
H
H
H
H
H
Me
Cl
H
H
H
H
H
8-Me
8-Me
7-Me
5,7-Me2
5,7-Me2
4-i-Pr
CO2Me
CO2Et
3
3
5
3
28
5
9
3
15
15
9
9
19
3
4(7)
20
4
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
97
98
95
98
4-i-Pr
4-i-Pr
2-Me
H
4-i-Pr
4-i-Pr
3-Me
4-Cl
CO2Bu-n
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
Fig. 2. Synthetic schedule of 12H-thiochromeno[2,3-b]quinolines and 5H-benzo[7,8]
thiocino[2,3-b]quinolines from 2-chloro-3-formylquinolines.
84
90
46c
98
9
5 (47)c
10 (67)c
43c
2. Results and discussion
10
11
12
13
14
15
16
17
2-Cl
4-Br
69c
63c
98
The starting 2-chloro-3-formylquinolines 1 were prepared from
the corresponding acetanilides by treatment with the Vilsmerier
reagent generated in situ from POCl3/DMF system.15 When we
mixed 2-chloro-3-formylquinolines 1a, 4-isopropylbenzenethiol,
and NaH in DMSO at 90 ꢀC for 2 h, the desired 2-(4-iso-
propylphenylthio)quinoline-3-carbaldehyde 2a was isolated in 82%
yield (Table 1, entry 1). Similarly, the corresponding compounds
2beo were prepared from 2-chloro-3-formylquinolines 1 with
moderate to high yields under the same conditions (Table 1). With
2-arylthioquinoline-3-carbaldehydes 2 in hand, we intended to test
the MBH reaction between 2 and activated alkenes in the presence
of DABCO at room temperature (Table 2). The desired compounds
3aef and 3h were obtained in 84e98% isolated yields (Table 2,
entries 1e8). Unfortunately, the substrates with electron-with-
drawing groups (2g and 2h) gave MBH adducts 3i and 3j in lower
yields with prolonged reaction times, respectively (Table 2, entries
9 and 10). Then we tried to use DMAP16 to promote this MBH re-
action, and it is gratifying to find that 3g and 3iel were successfully
isolated in moderate yields with CH2Cl2 as a solvent at room tem-
perature for 9 days. Similarly, the desired products 3m and 3n
derived from 8-position substituted quinolines 2k and 2l were
obtained in good yields (Table 2, entries 13 and 14). However the
2,4-Cl2
2,4-Cl2
4-Me
4-Me
2,4-Cl2
4-Me
Trace (10)c
6c
Trace
a
Conditions: 2 (2 mmol), alkene (10 mmol), DABCO (0.6 mmol), rt.
Isolated yields based on 2.
Conditions: 2 (2 mmol), alkene (10 mmol), DMAP (1 mmol), CH2Cl2, rt, 9 days.
b
c
5- or 7-position substituted quinolines gave the desired com-
pounds 3oeq in relatively low yields (Table 2, entries 15e17). It
seems that the substituent group plays an important role in
governing the reactivity of the substrates.
Encouraged by these results, we turned our attention to the
intramolecular FriedeleCrafts reaction of MBH adducts 3 (Scheme 1).
Preliminary experiments indicated that, the desired product 4a and/
or the expected eight-membered fused-ring 5a was not detected by
treatment of compound 3a in CH3NO2 or CH2Cl2 with various Lewis
acids, such as AlCl3, Zn(OTf)2, Yb(OTf)3 or BF3eOEt2 (Table 3, entries
1e5).17 Then CF3SO3H was employed and 4a was isolated in only 48%
yield (Table 3, entry 6).18 In order to optimize the reaction conditions,
various factors including the identity and amount of promoters,
solvents, reaction temperature were screened and the results were
summarized in Table 3. The Optimal conditions were obtained by the
treatment of 3a with 95% concentrated H2SO4 (preferly 8.0 equiv) in
CH2Cl2 atroomtemperature, providing4ain79%within1.5 h(Table 3,
entry 11).19
Table 1
Synthesis of 2-arylthioquinoline-3-carbaldehydes 2 from 2-chloro-3-formylquino-
lines 1a
HS
R2
CHO
S
CHO
Cl
R1
R1
NaH/DMSO
90 oC
N
N
R2
1
2
Entry
R1
R2
Time (h)
Products
Yieldb (%)
1
2
3
4
5
6
7
8
H
H
H
Me
Cl
H
H
H
H
4-i-Pr
2-Me
H
4-i-Pr
4-i-Pr
3-Me
4-Cl
2
3
3
2
2
2
3
3
3
4
3
2
2
3
2
2a
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
2n
2o
82
86
77
69
61
83
86
89
85
88
88
81
70
87
67
2-Cl
4-Br
9
10
11
12
13
14
15
H
2,4-Cl2
2,4-Cl2
4-Me
4-Me
2,4-Cl2
4-Me
Scheme 1. The intramolecular FriedeleCrafts reaction of 3a.
8-Me
8-Me
7-Me
5,7-Me2
5,7-Me2
Under the above optimized conditions, 4beg were obtained in
62e90% yields (Table 4, entries 2e7). Interestingly, treatment of 3h
with 95% concentrated H2SO4 gave a mixture of isomers 4h and 4h0
in 68% yield with a ratio of 1:1 (determined by 1H NMR spectra)
a
Conditions: 1 (10 mmol), thiophenol (11 mmol), NaH (20 mmol), DMSO (20 mL).
Isolated yields based on quinoline-3-aldehydes 1.
b

W. Zhong et al. / Tetrahedron 67 (2011) 3509e3518
3511
Table 3
MBH adducts could be performed and provided only the six-
membered fused-rings 4i, 4j, and 4l in 27e49% yields (Table 4,
entries 9, 10, and 12). The MBH adduct 3n derived from 8-po-
sition substituted quinoline gave the eight-membered fused-ring
5n in 57% yield and 4n in 21% yield (Table 4, entry 14). The
MBH adducts with electron-withdrawing groups required longer
reaction time and gave lower yields than those with electron-
donating groups (Table 4).
Inordertoextendthescope,thepreparationofcompound 4ofrom
2-chloro-3-formyl quinoline 1 was also investigated (Scheme 3).
Treatment of 1 with thiophene-2-thiol in the presence of NaH gave
2-(thiophen-2-ylthio)quinoline-3-carbaldehyde 2p in 70% yield,
which was then converted into MBH adduct 3r by treatment with
methyl acrylate in the presence of DABCO. Finally, the intramolecular
FriedeleCrafts reaction of 3r mediated by 95% concentrated H2SO4
could produce a six-membered fused-ring 4o in 50% yield.
Synthesis of 4a under various conditionsa
Entry Reagents Amount (equiv) Solvent Temp (ꢀC) Time (h) Yieldb (%)
1
2
3
4
5
6
7
8
AlCl3
AlCl3
Zn(OTf)2
1.1
3.0
0.5
CH3NO2 60
CH3NO2 60
CH3NO2 100
5
5
10
15
10
4
10
7
6
0
0
0
0
Yb(OTf)3 0.3
BF3eOEt2 1.0
CH2Cl2
CH2Cl2
Reflux
Reflux
0
CF3SO3H
3.0
(ClCH2)2 Reflux
48
Trace
Trace
24
33
79
95%H2SO4 1.2
95%H2SO4 2.0
95%H2SO4 4.0
95%H2SO4 6.0
95%H2SO4 8.0
DMF
rt
Reflux
rt
rt
rt
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
9
10
11
2
1.5
a
Reaction conditions: 3a (1 mmol), solvent (10 mL).
Isolated yield based on 3a.
b
(Scheme 2). To our delight, 95% concentrated H2SO4 mediated the
intramolecular FriedeleCrafts reaction of substrate 3i could give the
desired product 4i in 8% yield and the novel eight-membered fused-
ring 5i (sulfate!) was isolated with 63% yield (Table 4, entry 9).
Similarly, the corresponding products (5jem) were isolated in
66e82% yield when other substrates bearing electron-with-
drawing groups was used (Table 4, entries 10e13). While pro-
moted by CF3SO3H, the intramolecular FriedeleCrafts reaction of
Scheme 3. Synthesis of 4o from 2-chloro-3-formyl quinoline 1.
According to the above results, a plausible mechanism for the
formation of compounds 4 and 5 from MBH adducts 3 was shown
in Scheme 4.20 When the substrates 3 were treated with sulfuric or
triflic acid, the allyl cation intermediates 6 could be formed, which
were readily transformed into six-(path a) or eight-(path b)
membered fused-rings via intramolecular FriedeleCrafts reaction.
Scheme 2. The intramolecular FriedeleCrafts reaction of 3h.
Table 4
Synthesis of 12H-thiochromeno[2,3-b]quinolines 4 and 5H-benzo[7,8]thiocino[2,3-b]quinolines 5 from MBH adducts 3a
OH
EWG
EWG
EWG
R1
acid
R1
R1
R2
+
H2SO4
R2
N
S
N
N
S
R2
S
3
5
4
Entry
R1
R2
EWG
Time (h)
Isolated yields (%)b
Products (4)
Products (5)
1
2
3
4
5
6
7
8
H
H
H
H
H
4-Me
Cl
H
H
H
H
H
8-Me
8-Me
4-i-Pr
CO2Me
CO2Et
1.5
1.5
2.5
1.5
2.5
2.5
1
4a (79)
4b (83)
4c (67)
4d (90)
4e (62)
4f (83)
4g (68)
n.d.c
4-i-Pr
4-i-Pr
2-Me
H
4-i-Pr
4-i-Pr
3-Me
4-Cl
2-Cl
4-Br
2,4-Cl2
2,4-Cl2
4-Me
n.d.c
CO2Bu-n
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
n.d.c
n.d.c
n.d.c
n.d.c
n.d.c
2
4hþ4h0 (68)
4i (8/27)d
4j (7/49)d
4k (n.d.)c
4l (3/40)d
4m (n.d.)c
4n (21)
n.d.c
9
0.5 (6)
0.5 (6)
0.5
0.5
1
5i (63)
5j (66)
5k (82)
5l (66)
5m (73)
5n (57)
10
11
12
13
14
1.5
a
Conditions: 3 (1 mmol), 95%H2SO4 (8.0 mmol), CH2Cl2, rt.
Isolated yields based on 3.
b
c
n.d.¼not detected.
d
Conditions: 3 (1 mmol), CF3SO3H (3.0 mmol), ClCH2CH2Cl, reflux.

3512
W. Zhong et al. / Tetrahedron 67 (2011) 3509e3518
J¼8.0 Hz, ArH), 2.92e3.02 (m, 1H, CH(CH3)2), 1.30 (6H, d, J¼7.2 Hz,
CH(CH3)2); 13C NMR (100 MHz, CDCl3)
d¼190.0, 159.1, 149.7, 149.5,
142.1, 135.0 (2C), 132.7, 129.0, 128.6, 127.2, 127.1 (3C), 126.5, 125.1,
33.9, 23.8 (2C); MS (EI) m/z¼307 (Mþ, 16), 279 (52), 278 (100);
HRMS (EI) calcd for C19H17NOS (Mþ): 307.1043; found: 307.1046.
4.2.2. 2-(o-Tolylthio)quinoline-3-carbaldehyde (2b). Yellow solid;
mp 91.8e92.5 ꢀC (n-hexane/EtOAc); Rf¼0.46 (n-hexane/EtOAc, 4:1);
IR (KBr): 1694 (CHO) cmꢂ1; 1H NMR (400 MHz, CDCl3)
CHO), 8.51 (1H, s, ArH), 7.83 (1H, d, J¼8.0 Hz, ArH), 7.62e7.68 (2H, m,
ArH), 7.55 (1H, d, J¼8.0 Hz, ArH), 7.45 (1H, t, J¼7.6 Hz, ArH), 7.33e7.38
(2H, m, ArH), 7.20e7.24 (1H, m, ArH), 2.37 (3H, s, CH3); 13C NMR
d
¼10.38 (1H, s,
(100 MHz, CDCl3)
d
¼189.8, 158.3, 149.4, 143.0, 142.3, 136.0, 132.6,
130.3, 129.4, 129.0, 128.9, 128.5, 127.0, 126.3 (2C), 124.8, 21.0; MS (EI)
m/z¼279 (Mþ, 13), 250 (39), 236 (40), 218 (100); HRMS (EI) calcd for
C17H13NOS (Mþ): 279.0728; found: 279.0722.
Scheme 4. A plausible mechanism for the formation of 4 and 5.
4.2.3. 2-(Phenylthio)quinoline-3-carbaldehyde (2c). Yellow solid;
mp 136.1e136.9 ꢀC (n-hexane/EtOAc); Rf¼0.48 (n-hexane/EtOAc,
3. Conclusion
4:1); IR (KBr): 1686 (CHO) cmꢂ1; 1H NMR (400 MHz, CDCl3)
d¼10.37
(1H, s, CHO), 8.52 (1H, s, ArH), 7.84 (1H, d, J¼8.4 Hz, ArH), 7.68e7.70
In conclusion, we developed a new protocol for the synthesis of
12H-thiochromeno[2,3-b]quinolines 4 via sulfuric acid or triflic
acid-promoted intramolecular FriedeleCrafts reaction of MBH ad-
ducts. Very interestingly, those MBH adducts with electron-with-
drawing groups could give 5H-benzo[7,8]thiocino[2,3-b]quinolines
5 in moderate yields in the presence of sulfuric acid. This strategy is
attractive as it employs commonly available cheap reagents and
does not require any elaborate reaction conditions.
(2H, m, ArH), 7.58e7.60 (2H, m, ArH), 7.45e7.49 (1H, m, ArH),
7.40e7.42 (3H, m, ArH); 13C NMR (100 MHz, CDCl3)
149.6, 142.5, 135.2 (2C), 133.0, 130.1, 129.2, 129.1 (2C), 129.0, 128.81,
127.4, 126.8, 125.3; MS (EI) m/z¼265 (Mþ, 15), 237 (39), 236 (100);
HRMS (EI) calcd for C16H11NOS (Mþ): 265.0617; found: 265.0623.
d
¼190.1, 158.8,
4.2.4. 2-(4-Isopropylphenylthio)-6-methylquinoline-3-carbaldehyde
(2d). Yellow solid; mp 90.2e91.1 ꢀC (n-hexane/EtOAc); Rf¼0.46
(n-hexane/EtOAc, 4:1); IR (KBr): 1682 (CHO) cmꢂ1
;
1H NMR
4. Experimental
4.1. General
(400 MHz, CDCl3)
d
¼10.37 (1H, s, CHO), 8.42 (1H, s, ArH), 7.64 (1H, d,
J¼8.8 Hz, ArH), 7.58 (1H, s, ArH), 7.48e7.52 (3H, m, ArH), 7.26 (2H, d,
J¼8.0 Hz, ArH), 2.90e3.00 (1H, m, CH(CH3)2), 2.49 (3H, s, CH3), 1.29
(6H, d, J¼6.8 Hz, CH(CH3)2); 13C NMR (100 MHz, CDCl3)
¼190.3,
d
€
Melting points were determined using a Buchi B-540 capillary
158.0, 149.7, 148.4, 141.5, 136.8, 135.2, 134.9 (2C), 128.5, 128.0, 127.5,
127.3 (2C),127.2,125.4, 34.3, 24.3 (2C), 21.9; MS (EI) m/z¼321 (Mþ, 9),
293 (47), 292 (100); HRMS (EI) calcd for C20H19NOS (Mþ): 321.1252;
found: 321.1242.
melting point apparatus and were uncorrected. IR spectra were
recorded on a Nicolet Avatar-370 instrument. 1H and 13C NMR
spectra were recorded on Varian (400 MHz) instruments using
TMS as an internal standard. Mass spectra were measured with
a Finnigan Trace DSQ instrument or GCT Premier mass spec-
trometer. High-resolution mass spectral (HRMS) analyses were
measured on an APEX (Bruker) mass III spectrometer or GCT
Premier mass spectrometer using ESI (electrospray ionization) or
EI (electron impact) techniques. Silica gel for column chroma-
tography was purchased from Qingdao Haiyang Chemical Co., Ltd.
(200e300 mesh). All yields described herein are the isolated
yields after column chromatography.
4.2.5. 6-Chloro-2-(4-isopropylphenylthio)quinoline-3-carbaldehyde
(2e). Yellow solid; mp 100.1e101.0 ꢀC (n-hexane/EtOAc); Rf¼0.44
(n-hexane/EtOAc, 4:1); IR (KBr): 1686 (CHO) cmꢂ1
;
1H NMR
(400 MHz, CDCl3)
d
¼10.37 (1H, s, CHO), 8.40 (1H, s, ArH), 7.79 (1H,
d, J¼2.4 Hz, ArH), 7.63 (1H, d, J¼8.8 Hz, ArH), 7.58 (1H, dd, J¼8.8,
2.4 Hz, ArH), 7.50 (2H, d, J¼8.0 Hz, ArH), 7.28 (2H, d, J¼8.0 Hz, ArH),
2.92e3.02 (1H, m, CH(CH3)2), 1.30 (6H, d, J¼7.2 Hz, CH(CH3)2); 13C
NMR (100 MHz, CDCl3)
d
¼189.4, 159.5, 149.8147.6, 140.7, 135.0 (2C),
133.2, 131.9, 130.0, 127.5, 127.3, 127.1 (2C), 125.9, 125.5, 34.0, 24.0
(2C); MS (EI) m/z¼341 (Mþ,19), 314 (45), 312 (100); HRMS (EI) calcd
for C19H16ClNOS (Mþ): 341.0611; found: 341.0619.
4.2. General procedure for the preparation of 2-
arylthioquinoline-3-carbaldehyde 2
To a mixture of thiophenol (11 mmol), NaH (20 mmol), and
DMSO (20 mL) was added 2-chloro-3-formylquinolines 1 (10 mmol)
and the mixture was heated at 90 ꢀC for the given time. Then the
reaction was quenched with water (60 mL) and extracted with
CH2Cl2 (3ꢁ50 mL). The combined organic layer was washed with
brine solution, dried over anhydrous Na2SO4, and concentrated in
vacuo. The desired products 2 were obtained by flash column
chromatography on silica (n-hexane/EtOAc, 10:1/6:1, v/v).
4.2.6. 2-(m-Tolylthio)quinoline-3-carbaldehyde (2f). Yellow solid;
mp 97.8e98.5 ꢀC (n-hexane/EtOAc); Rf¼0.44 (n-hexane/EtOAc,
4:1); IR (KBr): 1692 (CHO) cmꢂ1 1H NMR (400 MHz, CDCl3)
;
d
¼10.37 (1H, s, CHO), 8.51 (1H, s, ArH), 7.84 (1H, d, J¼8.0 Hz, ArH),
7.73 (1H, d, J¼8.0 Hz, ArH), 7.66e7.71 (1H, m, ArH), 7.45e7.49 (1H,
m, ArH), 7.41 (1H, s, ArH), 7.38 (1H, d, J¼7.6 Hz, ArH), 7.30 (1H, t,
J¼7.6 Hz, ArH), 7.20 (1H, d, J¼7.6 Hz, ArH), 2.38 (3H, s, CH3); 13C
NMR (100 MHz, CDCl3)
d¼189.8, 158.7, 149.3, 141.9, 138.6, 135.1,
132.7, 131.8, 129.6, 129.5, 128.9, 128.6, 128.5, 127.2, 126.5, 125.1, 21.5;
MS (EI) m/z¼279 (Mþ, 13), 251 (47), 250 (100); HRMS (EI) calcd for
C17H13NOS (Mþ): 279.0733; found: 279.0745.
4.2.1. 2-(4-Isopropylphenylthio)quinoline-3-carbaldehyde
(2a). Yellow solid; mp 83.4e84.3 ꢀC (n-hexane/EtOAc); Rf¼0.45
(n-hexane/EtOAc, 4:1); IR (KBr): 1693 (CHO) cmꢂ1
;
1H NMR
(400 MHz, CDCl3)
J¼8.0 Hz, ArH), 7.75 (1H, d, J¼8.0 Hz, ArH), 7.69e7.73 (1H, m, ArH),
7.53 (2H, d, J¼8.0 Hz, ArH), 7.47e7.51 (1H, m, ArH), 7.30 (2H, d,
d
¼10.42 (1H, s, CHO), 8.54 (1H, s, ArH), 7.86 (1H, d,
4.2.7. 2-(4-Chlorophenylthio)quinoline-3-carbaldehyde (2g). Yellow
solid; mp 143.0e143.6 ꢀC (n-hexane/EtOAc); Rf¼0.41 (n-hexane/
EtOAc, 4:1); IR (KBr): 1690 (CHO) cmꢂ1; 1H NMR (400 MHz, CDCl3)

W. Zhong et al. / Tetrahedron 67 (2011) 3509e3518
3513
d
¼10.33 (1H, s, CHO), 8.52 (1H, s, ArH), 7.85 (1H, d, J¼8.0 Hz, ArH),
(n-hexane/EtOAc, 4:1); IR (KBr): 1689 (CHO) cmꢂ1
(400 MHz, CDCl3)
;
1H NMR
7.68e7.73 (2H, m, ArH), 7.53 (2H, d, J¼8.4 Hz, ArH), 7.47e7.51 (1H,
d
¼10.34 (1H, s, CHO), 8.44 (1H, s, ArH), 7.71 (1H,
m, ArH), 7.39 (2H, d, J¼8.4 Hz, ArH); 13C NMR (100 MHz, CDCl3)
d, J¼8.0 Hz, ArH), 7.47 (3H, d, J¼8.0 Hz, ArH), 7.28 (1H, dd, J¼8.0,
1.6 Hz, ArH), 7.23 (2H, d, J¼8.0 Hz, ArH), 2.47 (3H, s, CH3), 2.42 (3H,
d
¼189.7, 157.9, 149.2, 143.0, 136.5 (2C), 135.0, 132.9, 129.0 (2C),
128.8, 128.4, 128.1, 126.8, 126.6, 124.9; MS (EI) m/z¼299 (Mþ, 13),
272 (44), 270 (100); HRMS (EI) calcd for C16H10ClNOS (Mþ):
300.0239; found 300.0241.
s, CH3); 13C NMR (100 MHz, CDCl3)
d
¼189.8, 158.9, 149.5, 143.8,
141.8, 138.7, 134.9 (2C), 129.6 (2C), 128.6, 128.5, 127.6, 126.4, 126.2,
123.0, 22.2, 21.5; MS (EI) m/z¼293.1 (Mþ, 24), 265.1 (44), 264.1
(100); HRMS (EI) calcd for C18H15NOS (Mþ): 293.0874; found:
293.0897.
4.2.8. 2-(2-Chlorophenylthio)quinoline-3-carbaldehyde (2h). Yellow
solid; mp 110.2e111.3 ꢀC (n-hexane/EtOAc); Rf¼0.43 (n-hexane/
EtOAc, 4:1); IR (KBr): 1685 (CHO) cmꢂ1; 1H NMR (400 MHz, CDCl3)
4.2.14. 2-(2,4-Dichlorophenylthio)-5,7-dimethylquinoline-3-carbal-
dehyde (2n). Yellow solid; mp 198.7e199.1 ꢀC (n-hexane/EtOAc);
Rf¼0.45 (n-hexane/EtOAc, 4:1); IR (KBr): 1689 (CHO) cmꢂ1; 1H NMR
d
¼10.34 (1H, s, CHO), 8.53 (1H, s, ArH), 7.85 (1H, d, J¼8.0 Hz, ArH),
7.63e7.70 (3H, m, ArH), 7.53 (1H, d, J¼8.0 Hz, ArH), 7.47 (1H, t,
J¼7.6 Hz, ArH), 7.36e7.40 (1H, m, ArH), 7.3 (1H, t, J¼7.6 Hz, ArH);
(400 MHz, CDCl3)
d
¼10.33 (1H, s, CHO), 8.65 (1H, s, ArH), 7.61 (1H,
13C NMR (100 MHz, CDCl3)
d¼189.9, 157.0, 1128.5, 49.3, 142.9, 139.4,
d, J¼7.6 Hz, ArH), 7.58 (1H, d, J¼2.4 Hz, ArH), 7.32 (2H, dd, J¼8.0,
2.4 Hz, ArH), 7.18 (1H, s, ArH), 2.70 (3H, s, CH3), 2.47(3H, s, CH3); 13
NMR (100 MHz, CDCl3)
138.0, 135.9, 135.7, 129.7, 129.5, 128.3, 127.3, 125.9, 125.7, 122.6, 22.1,
18.6; MS (EI) m/z¼361.0 (Mþ, 1), 328.0 (44), 326.0 (100), 298.0 (48);
HRMS (EI) calcd for C18H13Cl2NOS (Mþ): 361.0095; found: 361.0125.
137.1, 132.8, 130.4, 129.8, 129.4, 128.8, 127.03, 126.95, 126.5, 124.9;
MS (ESI) m/z¼300.2 (Mþþ1, 100); HRMS (ESI) calcd for
C16H10ClNOS (Mþ): 299.0250; found: 299.0249.
C
d
¼189.9, 156.2, 150.0, 143.9, 140.5, 139.6,
4.2.9. 2-(4-Bromophenylthio)quinoline-3-carbaldehyde (2i). Yellow
solid; mp 150.2e150.9 ꢀC (n-hexane/EtOAc); Rf¼0.43 (n-hexane/
EtOAc, 4:1); IR (KBr): 1689 (CHO) cmꢂ1; 1H NMR (400 MHz, CDCl3)
4.2.15. 5,7-Dimethyl-2-(p-tolylthio)quinoline-3-carbaldehyde
d
¼10.33 (1H, s, CHO), 8.52 (1H, s, ArH), 7.86 (1H, d, J¼8.0 Hz, ArH),
(2o). Yellow solid; mp 184.0e184.7 ꢀC (n-hexane/EtOAc); Rf¼0.47
7.70 (2H, s, ArH), 7.45e7.56 (5H, m, ArH); 13C NMR (100 MHz,
(n-hexane/EtOAc, 4:1); IR (KBr): 1697 (CHO) cmꢂ1
;
1H NMR
CDCl3)
d
¼189.7, 157.8, 149.2, 143.0, 136.7 (2C), 132.9, 131.9 (2C),
(400 MHz, CDCl3)
d
¼10.37 (1H, s, CHO), 8.60 (1H, s, ArH), 7.46 (2H,
128.9, 128.7, 128.4, 126.8, 126.6, 124.9, 123.3; MS (EI) m/z¼343 (Mþ,
13), 317 (35), 316 (100), 315 (35), 314 (92), 238 (40); HRMS (EI) calcd
for C16H10BrNOS (Mþ): 342.9763; found: 342.9781.
d, J¼8.0 Hz, ArH), 7.34 (1H, s, ArH), 7.22 (2H, d, J¼8.0 Hz, ArH), 7.12
(1H, s, ArH), 2.65 (3H, s, CH3), 2.42 (6H, d, J¼4.4 Hz, CH3); 13C NMR
(100 MHz, CDCl3)
d
¼189.9, 158.5, 150.2, 143.5, 138.6, 138.1, 136.0,
134.8 (2C), 129.8, 129.6 (2C), 129.3, 126.5, 125.9, 122.7, 22.1, 21.5,
18.6; MS (EI) m/z¼307.1 (Mþ, 16), 279.1 (46), 278.1 (100); HRMS (EI)
calcd for C19H17NOS (Mþ): 307.1031; found: 307.1056.
4.2.10. 2-(2,4-Dichlorophenylthio)quinoline-3-carbaldehyde
(2j). Yellow solid; mp 138.2e139.1 ꢀC (n-hexane/EtOAc); Rf¼0.42
(n-hexane/EtOAc, 4:1); IR (KBr): 1691 (CHO) cmꢂ1
;
1H NMR
(400 MHz, CDCl3)
d
¼10.31 (1H, s, CHO), 8.53 (1H, s, ArH), 7.86 (1H,
4.2.16. 2-(Thiophen-2-ylthio)quinoline-3-carbaldehyde (2p). Yellow
solid; mp 118.8e119.7 ꢀC (n-hexane/EtOAc); Rf¼0.45 (n-hexane/
EtOAc, 4:1); IR (KBr): 1698 (CHO) cmꢂ1; 1H NMR (400 MHz, CDCl3)
d, J¼8.0 Hz, ArH), 7.65e7.73 (2H, m, ArH), 7.60 (1H, d, J¼8.4 Hz,
ArH), 7.56 (1H, d, J¼2.0 Hz, ArH), 7.47e7.51 (1H, m, ArH), 7.30 (1H,
dd, J¼8.4, 2.0 Hz, ArH); 13C NMR (100 MHz, CDCl3)
d
¼189.9, 156.6,
d
¼10.29 (1H, d, J¼4.4 Hz, CHO), 8.50 (1H, d, J¼4.8 Hz, ArH), 7.85
149.2, 143.5, 140.6, 138.1, 135.9, 133.0, 129.8, 128.9, 128.6, 128.0,
127.4, 126.8, 126.7, 124.9; MS (EI) m/z¼333 (Mþ, 1), 300 (36), 298
(100), 270 (39); HRMS (EI) calcd for C16H9Cl2NOS (Mþ): 332.9826;
found: 332.9835.
(1H, dd, J¼8.0, 2.4 Hz, ArH), 7.78 (1H, dd, J¼8.0 Hz, 2.4 Hz, ArH), 7.72
(1H, t, J¼7.2 Hz, ArH), 7.49 (1H, t, J¼7.2 Hz, ArH), 7.60 (1H, d,
J¼5.2 Hz, ArH), 7.34 (1H, d, J¼3.6 Hz, ArH), 7.13 (1H, t, J¼4.0 Hz,
ArH); 13C NMR (100 MHz, CDCl3)
d
¼189.7, 158.2, 149.2, 143.4, 135.4,
133.0, 131.6, 128.8, 128.5, 127.2, 127.1, 126.6 (2C), 124.9; MS (EI) m/
z¼271 (Mþ, 41), 243 (62), 242 (100), 128 (53); HRMS (EI) calcd for
C14H9NOS2 (Mþ): 271.0189; found: 271.0196.
4.2.11. 2-(2,4-Dichlorophenylthio)-8-methylquinoline-3-carbalde-
hyde (2k). Yellow solid; mp 152.3e153.1 ꢀC (n-hexane/EtOAc);
Rf¼0.45 (n-hexane/EtOAc, 4:1); IR (KBr): 1687 (CHO) cmꢂ1; 1H NMR
(400 MHz, CDCl3)
d
¼11.28 (1H, s, CHO), 8.48 (1H, s, ArH), 7.69 (1H,
4.3. General procedure for the preparation of MBH adducts 3
d, J¼7.6 Hz, ArH), 7.62 (1H, d, J¼8.4 Hz, ArH), 7.58(1H, d, J¼2.4 Hz,
ArH), 7.54(1H, d, J¼2.4 Hz, ArH), 7.37 (1H, t, J¼7.6 Hz, ArH), 7.31(1H,
dd, J¼8.4, 2.4 Hz, ArH), 2.21(3H, s, CH3); 13C NMR (100 MHz, CDCl3)
A
mixture of compounds 2 (2 mmol), activated olefins
(10 mmol), and DABCO (0.6 mmol) or (DMAP (1 mmol) in CH2Cl2
(10 mL)) was kept at room temperature for the given time. Then the
mixture was extracted with CH2Cl2 (3ꢁ15 mL) and water (20 mL).
The combined organic layer was washed with brine solution
(3ꢁ15 mL), dried over anhydrous Na2SO4, and concentrated in
vacuo. The desired product 3 was obtained by flash column chro-
matography on silica (n-hexane/EtOAc, 6:1, v/v).
d
¼190.3, 155.6, 148.2, 144.4, 141.5, 138.7, 136.9, 136.2, 133.4, 129.9,
128.6,127.7,126.9,126.7 (2C),125.0,17.3; MS (EI) m/z¼347.0 (Mþ, 4),
314.0 (43), 312.0 (100), 284.0 (33); HRMS (EI) calcd for
C17H11Cl2NOS (Mþ): 346.9938; found: 346.9965.
4.2.12. 8-Methyl-2-(p-tolylthio)quinoline-3-carbaldehyde
(2l). Yellow solid; mp 101.6e102.4 ꢀC (n-hexane/EtOAc); Rf¼0.44
(n-hexane/EtOAc, 4:1); IR (KBr): 1693 (CHO) cmꢂ1
;
1H NMR
4.3.1. Methyl 2-(hydroxy(2-(4-isopropylphenylthio)quinolin-3-yl)
methyl)acrylate (3a). White solid; mp 123.6e124.7 ꢀC (n-hexane/
EtOAc); Rf¼0.55 (n-hexane/EtOAc, 2:1); IR (KBr): 3422 (OH), 1726
(400 MHz, CDCl3)
d
¼10.33 (1H, s, CHO), 8.43 (1H, s, ArH), 7.64(1H,
d, J¼8.0 Hz, ArH), 7.51(3H, d, J¼8.0 Hz, ArH), 7.32(1H, J¼8.0 Hz,
ArH), 7.24(2H, d, J¼8.0 Hz, ArH), 2.42(3H, s, CH3), 2.24(3H, s, CH3);
(CO2CH3) cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
¼8.19 (1H, s, ArH),
13C NMR (100 MHz, CDCl3)
d
¼190.2, 158.3, 148.4, 143.0, 139.1, 136.9,
7.79 (1H, d, J¼8.0 Hz), 7.75 (1H, d, J¼8.0 Hz), 7.56e7.60 (1H, m),
7.49 (2H, d, J¼8.0 Hz, ArH), 7.41e7.45 (1H, m, ArH), 7.24 (2H, d,
J¼8.0 Hz, ArH), 6.42 (1H, s, ]CHH), 6.15 (1H, s, ]CHH), 5.70 (1H,
s, CHOH), 3.80 (3H, s, OCH3), 3.45 (1H, s, OH), 2.89e2.99 (1H, m,
CH(CH3)2), 1.28 (6H, d, J¼6.8 Hz, CH(CH3)2); 13C NMR (100 MHz,
135.9 (2C), 133.1, 129.8 (2C), 126.9, 126.8, 126.4, 126.3, 125.0, 21.8,
17.4; MS (EI) m/z¼293.1 (Mþ, 43), 264.1 (100); HRMS (EI) calcd for
C18H15NOS (Mþ): 293.0874; found: 293.0887.
4.2.13. 7-Methyl-2-(p-tolylthio)quinoline-3-carbaldehyde
(2m). Yellow solid; mp 155.2e156.3 ꢀC (n-hexane/EtOAc); Rf¼0.44
CDCl3)
d
¼167.2, 157.6, 149.6, 147.8, 140.7, 134.6 (2C), 134.4, 133.3,
129.9, 128.6, 128.04, 127.99, 127.9, 127.4 (2C), 126.7, 126.3, 69.0,

3514
W. Zhong et al. / Tetrahedron 67 (2011) 3509e3518
52.6, 34.2, 24.2 (2C); MS (ESI) m/z¼394.2 (Mþþ1, 100); HRMS
133.4, 133.1, 131.7, 128.0, 127.9, 127.5, 126.9 (2C), 126.4, 126.3, 68.7,
52.3, 33.9, 24.0 (2C), 21.6; MS (EI) m/z¼407 (Mþ, 6), 349 (28), 348
(100); HRMS (EI) calcd for C24H25NO3S (Mþ): 407. 1686; found:
407.1694.
(ESI) calcd for C23H23NO3S (Mþ): 393.1472; found: 393.1458.
4.3.2. Ethyl 2-(hydroxy(2-(4-isopropylphenylthio)quinolin-3-yl)methyl)
acrylate (3b). White solid; mp 103.9e105.0 ꢀC (n-hexane/EtOAc);
Rf¼0.56 (n-hexane/EtOAc, 2:1); IR (KBr): 3423 (OH), 1720 (CO2Et)
4.3.7. Methyl 2-((6-chloro-2-(4-isopropylphenylthio)quinolin-3-yl)
cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
¼8.17 (1H, s, ArH), 7.76 (1H, d,
(hydroxy)methyl)acrylate (3g). Yellow oil; Rf¼0.53 (n-hexane/
J¼8.0 Hz, ArH), 7.73 (1H, d, J¼8.0 Hz, ArH), 7.54e7.58 (1H, m, ArH),
7.47 (2H, d, J¼8.0 Hz, ArH), 7.39e7.43 (1H, m, ArH), 7.23 (2H, d,
J¼8.0 Hz, ArH), 6.40 (1H, s, ]CHH), 6.13 (1H, s, ]CHH), 5.68 (1H, s,
CHOH), 4.24 (2H, q, J¼7.2 Hz, OCH2CH3), 3.48 (1H, s, OH), 2.93 (1H, m,
CH(CH3)2), 1.27e1.31 (9H, m, CH(CH3)2, and OCH2CH3); 13C NMR
EtOAc, 2:1); IR (neat): 3433 (OH), 1724 (CO2CH3) cmꢂ1 1H NMR
;
(400 MHz, CDCl3)
d
¼8.07 (1H, s, ArH), 7.69 (1H, d, J¼2.0 Hz, ArH),
7.65 (1H, d, J¼8.8 Hz, ArH), 7.44e7.48 (3H, m, ArH), 7.23 (2H, d,
J¼8.0 Hz, ArH), 6.41 (1H, s, ]CHH), 6.09 (1H, s, ]CHH), 5.67 (1H, s,
CHOH), 3.79 (3H, s, OCH3), 3.59 (1H, s, OH), 2.89e2.99 (1H, m, CH
(CH3)2), 1.28 (6H, d, J¼7.2 Hz, CH(CH3)2); 13C NMR (100 MHz, CDCl3)
(100 MHz, CDCl3)
d
¼166.6, 157.5, 149.4, 147.6, 140.8, 134.5 (2C), 134.2,
133.2, 129.7, 128.5, 127.9, 127.8,127.6, 127.3 (2C), 126.6, 126.1, 69.1, 61.6,
34.3, 24.3 (2C), 14.6; MS (ESI) m/z¼408.3 (Mþþ1, 100); HRMS (ESI)
calcd for C24H25NO3S (Mþ): 407.1636; found: 407.1629.
d
¼166.6, 157.8, 149.4, 145.6, 140.0, 134.5 (2C), 133.6, 132.8, 131.2,
130.2,129.7,127.8,127.0 (3C),126.7,126.2, 68.5, 52.4, 34.0, 24.0 (2C);
MS (ESI) m/z¼428.3 (Mþþ1, 100); HRMS (ESI) calcd for
C23H22ClNO3S (Mþ): 427.1054; found: 427.1051.
4.3.3. Butyl 2-(hydroxy(2-(4-isopropylphenylthio)quinolin-3-yl)methyl)
acrylate (3c). Yellow oil; Rf¼0.55 (n-hexane/EtOAc, 2:1); IR (neat):
4.3.8. Methyl 2-(hydroxy(2-(m-tolylthio)quinolin-3-yl)methyl)acry-
3431 (OH), 1716 (CO2Bu-n) cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d¼8.16
late (3h). Colorless oil; Rf¼0.53 (n-hexane/EtOAc, 2:1); IR (neat):
(1H, s, ArH), 7.76 (1H, d, J¼8.0 Hz, ArH), 7.32 (1H, d, J¼8.0 Hz, ArH),
7.56 (1H, t, J¼8.0 Hz, ArH), 7.47 (2H, d, J¼8.0 Hz, ArH), 7.41 (1H, t,
J¼8.0 Hz, ArH), 7.23 (2H, d, J¼8.0 H, ArH), 6.41 (1H, s, ]CHH), 6.13 (1H,
s, ]CHH), 5.70 (1H, s, CHOH), 4.13e4.22 (2H, m, OCH2CH2CH2CH3),
3.46 (1H, s, OH), 2.88e2.99 (1H, m, CH(CH3)2), 1.59e1.66 (2H, m,
OCH2CH2CH2CH3), 1.29e1.38 (2H, m, OCH2CH2CH2CH3), 1.28 (6H, d,
J¼6.8 Hz, CH(CH3)2), 0.88 (3H, t, J¼7.2 Hz, OCH2CH2CH2CH3); 13C NMR
3408 (OH), 1722 (CO2CH3) cmꢂ1; 1H NMR (400 MHz, CDCl3)
d¼8.18
(1H, s, ArH), 7.76 (1H, d, J¼8.0 Hz, ArH), 7.73 (1H, d, J¼8.0 Hz, ArH),
7.56 (1H, t, J¼8.4 Hz, ArH), 7.41 (1H, t, J¼8.0 Hz, ArH), 7.35 (1H, s,
ArH), 7.32 (1H, d, J¼8.0 Hz, ArH), 7.23 (1H, t, J¼7.6 Hz, ArH), 7.14
(1H, d, J¼7.6 Hz, ArH), 6.40 (1H, s, ]CHH), 6.13 (1H, s, ]CHH), 5.69
(1H, s, CHOH), 3.78 (3H, s, OCH3), 3.50 (1H, s, OH), 2.34 (3H, s, CH3);
13C NMR (100 MHz, CDCl3)
d
¼167.0, 157.1, 147.6, 140.6, 138.8, 134.7,
(100 MHz, CDCl3)
d
¼166.3, 157.2, 149.1, 147.3, 140.5, 134.2 (2C), 133.9,
134.3, 133.3, 131.3, 130.9, 129.8, 129.3, 128.9, 128.5, 127.94, 127.87,
126.6, 126.3, 69.0, 52.6, 21.8; MS (EI) m/z¼365 (Mþ, 5), 307 (27), 306
(100); HRMS (EI) calcd for C21H19NO3S (Mþ): 365.1179; found:
365.1194.
132.9,129.4,128.2,127.5,127.4,127.3,127.0 (2C),126.2,125.8, 68.7, 65.1,
34.0, 30.6, 24.0 (2C), 19.2, 13.8; MS (EI) m/z¼435 (Mþ, 4), 334 (100);
HRMS (EI) calcd for C26H29NO3S (Mþ): 435.1966; found: 435.1961.
4.3.4. Methyl 2-(hydroxy(2-(o-tolylthio)quinolin-3-yl)methyl) acry-
4.3.9. Methyl 2-((2-(4-chlorophenylthio)quinolin-3-yl)(hydroxy)methyl)
late (3d). White solid; mp 82.7e83.5 ꢀC (n-hexane/EtOAc); Rf¼0.57
acrylate (3i). White solid; mp 121.3e121.9 ꢀC(n-hexane/EtOAc); Rf¼0.51
(n-hexane/EtOAc, 2:1); IR (KBr): 3287 (OH), 1725 (CO2CH3) cmꢂ1
;
(n-hexane/EtOAc, 2:1); IR (KBr): 3276 (OH), 1723 (CO2CH3) cmꢂ1 1H
;
1H NMR (400 MHz, CDCl3)
d¼8.17 (1H, s, ArH), 7.72 (1H, d, J¼8.0 Hz,
NMR (400 MHz, CDCl3)
d
¼8.18 (1H, s, ArH), 7.74 (2H, d, J¼8.0 Hz, ArH),
ArH), 7.66 (1H, d, J¼8.0 Hz, ArH), 7.49e7.54 (2H, m, ArH), 7.39 (1H, t,
J¼7.2 Hz, ArH), 7.28e7.31 (2H, m, ArH), 7.17e7.21 (1H, m, ArH), 6.42
(1H, s, ]CHH), 6.13 (1H, s, ]CHH), 5.70 (1H, s, CHOH), 3.79 (3H, s,
OCH3), 3.49 (1H, s, OH), 2.30 (3H, s, CH3); 13C NMR (100 MHz,
7.55e7.60 (1H, m, ArH), 7.47 (2H, d, J¼8.4 Hz, ArH), 7.41e7.45 (1H, m,
ArH), 7.34 (2H, d, J¼8.4 Hz, ArH), 6.42 (1H, s, ]CHH), 6.09 (1H, s, ]CHH),
5.69 (1H, s, CHOH), 3.80 (3H, s, OCH3), 3.46 (1H, s, OH); 13C NMR
(100 MHz, CDCl3)
d
¼166.6, 156.2, 147.3, 140.2, 135.6 (2C), 134.4, 134.1,
CDCl3)
d
¼166.7, 156.7, 147.4, 142.3, 140.3, 135.6, 133.7, 132.5, 130.3,
132.6, 129.7, 129.1, 128.9 (2C), 128.1, 127.7, 127.6, 126.2, 126.1, 68.6, 52.4;
MS (ESI) m/z¼386.2 (Mþþ1, 100); HRMS (ESI) calcd for C20H16ClNO3S
(Mþ): 385.0576; found: 385.0573.
129.7, 129.4, 129.0, 128.1, 127.5 (2C), 126.2, 126.0, 125.7, 68.7, 52.3,
21.0; MS (ESI) m/z¼366.2 (Mþþ1, 100); HRMS (ESI) calcd for
C21H19NO3S (Mþ): 365.1164; found: 365.1168.
4.3.10. Methyl 2-((2-(2-chlorophenylthio)quinolin-3-yl)(hydroxy)
4.3.5. Methyl 2-(hydroxy(2-(phenylthio)quinolin-3-yl)methyl) acry-
late (3e). White solid; mp 111.3e112.2 ꢀC (n-hexane/EtOAc);
Rf¼0.56 (n-hexane/EtOAc, 2:1); IR (KBr): 3304 (OH), 1725 (CO2CH3)
methyl)acrylate (3j). Colorless oil; Rf¼0.52 (n-hexane/EtOAc,
2:1); IR (neat): 3435 (OH), 1723 (CO2CH3) cmꢂ1
;
1H NMR
(400 MHz, CDCl3)
d
¼8.22 (1H, s, ArH), 7.76 (1H, d, J¼8.0 Hz, ArH),
cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
¼8.18 (1H, s, ArH), 7.72e7.53 (2H,
7.72 (1H, d, J¼8.0 Hz, ArH), 7.55e7.59 (2H, m, ArH), 7.42e7.48 (2H,
m, ArH), 7.31 (1H, ddd, J¼24.8, 7.6, 1.6 Hz, ArH), 7.26 (1H, dd,
J¼7.6, 1.6 Hz, ArH), 6.43 (1H, s, ]CHH), 6.14 (1H, s, ]CHH), 5.73
(1H, s, CHOH), 3.80 (3H, s, OCH3), 3.48 (1H, s, OH); 13C NMR
m, ArH), 7.52e7.58 (3H, m, ArH), 7.41 (1H, t, J¼8.0 Hz, ArH),
7.34e7.39 (3H, m, ArH), 6.41 (1H, s, ]CHH), 6.13 (1H, s, ]CHH),
5.69 (1H, s, CHOH), 3.78 (3H, s, OCH3), 3.48 (1H, s, OH); 13C NMR
(100 MHz, CDCl3)
d
¼166.6, 156.7, 147.3, 140.3, 134.0 (3C), 132.9,
(100 MHz, CDCl3)
d
¼166.6, 155.5, 147.4, 140.2, 137.9, 136.0, 134.1,
130.9, 129.5, 128.7 (2C), 128.1 (2C), 127.64, 127.55, 126.3, 126.0, 68.7,
52.3; MS (EI) m/z¼351 (Mþ, 5), 293 (23), 292 (100); HRMS (EI) calcd
for C20H17NO3S (Mþ): 351.0953; found: 351.0938.
133.1, 130.6, 129.8, 129.63, 129.56, 128. 3, 127.8, 127.6, 126.9, 126.3,
126.1, 68.9, 52.3; MS (ESI) m/z¼386.2 (Mþþ1, 100); HRMS (ESI)
calcd for C20H16ClNO3S (Mþ): 385.0576; found: 385.0575.
4.3.6. Methyl2-(hydroxy(2-(4-isopropylphenylthio)-6-methylquinolin-
3-yl)methyl)acrylate (3f). Yellow oil; Rf¼0.52 (n-hexane/EtOAc, 2:1);
IR (neat): 3406 (OH),1724 (CO2CH3) cmꢂ1; 1H NMR (400 MHz, CDCl3)
4.3.11. Methyl
2-((2-(4-bromophenylthio)quinolin-3-yl)(hydroxy)
methyl)acrylate (3k). Yellow solid; mp 98.7e99.6 ꢀC (n-hexane/
EtOAc); Rf¼0.55 (n-hexane/EtOAc, 2:1); IR (KBr): 3435 (OH), 1723
d
¼8.08 (1H, s, ArH), 7.68 (1H, d, J¼8.4 Hz, ArH), 7.49 (1H, s, ArH), 7.44
(CO2CH3) cmꢂ1; 1H NMR (400 MHz, CDCl3)
d¼8.19 (1H, s, ArH), 7.74
(2H, d, J¼8.0 Hz, ArH), 7.39 (1H, dd, J¼8.4, 1.6 Hz, ArH), 7.20 (2H, d,
J¼8.0 Hz, ArH), 6.38 (1H, s, ]CHH), 6.12 (1H, s, ]CHH), 5.66 (1H, s,
CHOH), 3.77 (3H, s, OCH3), 3.46 (1H, s, OH), 2.87e2.97 (1H, m, CH
(CH3)2), 2.47 (3H, s, CH3), 1.26 (6H, d, J¼6.8 Hz, CH(CH3)2); 13C NMR
(2H, d, J¼8.4 Hz, ArH), 7.58 (1H, t, J¼8.0 Hz, ArH), 7.49 (2H, d,
J¼8.4 Hz, ArH), 7.39e7.45 (3H, m, ArH), 6.42 (1H, s, ]CHH), 6.09
(1H, s, ]CHH), 5.69 (1H, s, CHOH), 3.80 (3H, s, OCH3), 3.50 (1H, s,
OH); 13C NMR (100 MHz, CDCl3)
d¼166.6, 156.1, 147.3, 140.2, 135.7
(100 MHz, CDCl3)
d¼166.7155.8, 148.9, 146.0, 140.4, 135.8, 133.7 (2C),
(2C), 134.1, 132.6, 131.8 (2C), 129.8, 129.7, 128.1, 127.7, 127.6, 126.3,

W. Zhong et al. / Tetrahedron 67 (2011) 3509e3518
3515
126.1, 122.6, 68.6, 52.4; MS (ESI) m/z¼430.1 (Mþþ1, 100); HRMS
(Mþþ1, 100); HRMS (ESI) calcd for C22H19Cl2NO3S (Mþ): 447.0541;
(ESI) calcd for C20H16BrNO3S (Mþ): 429.0084; found: 429.0071.
found: 447.0558.
4.3.12. Methyl 2-((2-(2,4-dichlorophenylthio)quinolin-3-yl)(hydroxy)
methyl)acrylate (3l). White solid; mp 108.3e109.5 ꢀC (n-hexane/
EtOAc); Rf¼0.56 (n-hexane/EtOAc, 2:1); IR (KBr): 3435 (OH), 1723
4.3.17. Methyl 2-(hydroxy(2-(thiophen-2-ylthio)quinolin-3-yl)methyl)
acrylate (3r). White solid; mp 87.2e87.9 ꢀC (n-hexane/EtOAc);
Rf¼0.58 (n-hexane/EtOAc, 2:1); IR (KBr): 3286 (OH), 1723 (CO2CH3)
(CO2CH3) cmꢂ1; 1H NMR (400 MHz, CDCl3)
d¼8.21 (1H, s, ArH), 7.76
cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
¼8.15 (1H, s, ArH), 7.79 (1H, d,
(1H, d, J¼8.0 Hz, ArH), 7.72 (1H, d, J¼8.0 Hz, ArH), 7.56e7.60 (1H, m,
ArH), 7.53 (1H, d, J¼8.4 Hz, ArH), 7.49 (1H, d, J¼2.0 Hz, ArH),
7.42e7.46 (1H, m, ArH), 7.25 (1H, dd, J¼8.4, 2.4 Hz, ArH), 6.44 (1H, s,
]CHH), 6.11 (1H, s, ]CHH), 5.73 (1H, s, CHOH), 3.80 (3H, s, OCH3),
J¼8.0 Hz, ArH), 7.73 (1H, d, J¼8.0 Hz, ArH), 7.57 (1H, t, J¼7.2 Hz, ArH),
7.54 (1H, dd, J¼5.2, 0.8 Hz, ArH), 7.41 (1H, t, J¼7.2 Hz, ArH), 7.31 (1H,
dd, J¼3.2,1.2 Hz, ArH), 7.08 (1H, dd, J¼5.2, 3.6 Hz, ArH), 6.42 (1H, s, ]
CHH), 6.09 (1H, s, ]CHH), 5.70 (1H, s, CHOH), 3.79 (3H, s, OCH3), 3.50
3.52 (1H, s, OH); 13C NMR (100 MHz, CDCl3)
d
¼166.9, 155.5, 147.6,
(1H, s, OH); 13C NMR (100 MHz, CDCl3)
135.3, 133.9, 131.9, 131.3, 129.6, 128.1, 127.8, 127.6 (2C), 127.0, 126.2,
126.0, 68.5, 52.4; MS (EI) m/z¼357 (Mþ, 7), 299 (23), 298 (100);
HRMS (EI) calcd for C18H15NO3S2 (Mþ): 357.0528; found: 357.0533.
d
¼166.6, 156.6, 147.3, 140.1,
140.4, 139.3, 137.4, 135.5, 134.6, 133.1, 130.0 (2C), 129.3, 128.4, 128.1,
127.9, 127.6, 126.6, 126.5, 69.2, 52.7; MS (ESI) m/z¼420.1 (Mþþ1,
100); HRMS (ESI) calcd for C20H15Cl2NO3S (Mþ): 419.0143; found:
419.0129.
4.4. General procedure for the preparation of 4 and 5
4.3.13. Methyl 2-((2-(2,4-dichlorophenylthio)-8-methylquinolin-3-
yl)(hydroxy)methyl)acrylate (3m). Yellow oil; Rf¼0.53 (n-hexane/
Method A: A stirred solution of 3 (1 mmol), CH2Cl2 (10 mL), and
95% concentrated H2SO4 (8 mmol) was kept at room temperature for
the given time. The mixture was concentrated in vacuo and extrac-
ted with EtOAc (3ꢁ15 mL). The combined organic layer was washed
in turns with 15% sodium carbonate solution (20 mL) and brine
solution (3ꢁ15 mL), dried over anhydrous Na2SO4, and concentrated
in vacuo. The desired products 4aeh0, 4n, and 4o were obtained by
flash column chromatography on silica (n-hexane/EtOAc, 16:1, v/v).
Method B: A stirred solution of 3 (1 mmol), ClCH2CH2Cl (10 mL),
and CF3SO3H (3 mmol) was heated at reflux for the given time. The
mixture was extracted with CH2Cl2 (3ꢁ15 mL) and the combined
organic layer was washed in turns with 15% sodium carbonate
solution (20 mL) and brine solution (3ꢁ15 mL), dried over anhy-
drous Na2SO4, and concentrated in vacuo. The desired products
4iej and 4l were obtained by flash column chromatography on
silica (n-hexane/EtOAc, 16:1, v/v).
Method C: A stirred solution of 3 (1 mmol), CH2Cl2 (10 mL), and
95% concentrated H2SO4 (8 mmol) was kept at room temperature for
the given time. Then the mixture was concentrated in vacuo and
followed by addition of EtOAc (20 mL). When the pH value of this
system was adjusted to over 12 with 15% sodium hydroxide solution
(20 mL), a deposit was formed and filtered. The crude products were
re-crystallized from ethanol to give the desired products 5ien.
EtOAc, 2:1); IR (neat): 3393 (OH), 1707 (CO2CH3) cmꢂ1 1H NMR
;
(400 MHz, CDCl3)
d
¼8.14 (1H, s, ArH), 7.63 (1H, d, J¼8.0 Hz, ArH),
7.58 (1H, d, J¼8.0 Hz, ArH), 7.55 (1H, d, J¼2.0 Hz, ArH), 7.40 (1H, d,
J¼6.8 Hz, ArH), 7.31 (2H, t, J¼7.2 Hz, ArH), 6.46 (1H, s, ]CHH), 6.07
(1H, s, ]CHH), 5.75 (1H, s, CHOH), 3.81 (3H, s, OCH3), 3.47 (1H, d,
J¼4.4 Hz, OH), 2.27 (3H, s, CH3); 13C NMR (100 MHz, CDCl3)
d
¼166.7, 154.1, 146.1, 140.4, 140.0, 138.3, 136.1, 135.6, 134.2, 131.6,
129.7, 129.6, 128.7, 127.8, 127.2, 126.0, 125.8, 125.5, 68.9, 52.4, 17.1;
MS (ESI) m/z¼434.2 (Mþþ1, 100); HRMS (ESI) calcd for
C21H17Cl2NO3S (Mþ): 433.0384; found: 433.0385.
4.3.14. Methyl 2-(hydroxy(8-methyl-2-(p-tolylthio)quinolin-3-yl)met
hyl)acrylate (3n). Colorless oil; Rf¼0.56 (n-hexane/EtOAc, 2:1); IR
(neat): 3435 (OH), 1723 (CO2CH3) cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
¼8.10 (1H, s, ArH), 7.55 (1H, d, J¼8.0 Hz, ArH), 7.50 (2H, d, J¼8.4 Hz,
ArH), 7.38 (1H, d, J¼7.2 Hz, ArH), 7.27 (1H, t, J¼7.2 Hz, ArH), 7.20
(2H, d, J¼8.0 Hz, ArH), 6.43 (1H, s, ]CHH), 6.09 (1H, s, ]CHH), 5.73
(1H, s, CHOH), 3.80 (3H, s, OCH3), 3.42 (1H, d, J¼4.4 Hz, OH), 2.40
(3H, s, CH3), 2.32 (3H, s, CH3); 13C NMR (100 MHz, CDCl3)
d¼166.7,
156.3, 146.1, 140.1, 138.6, 136.0, 135.4 (2C), 133.8, 131.7, 129.5, 129.4
(2C), 127.7, 126.5, 125.9, 125.42, 125.39, 68.7, 52.3, 21.5, 17.3; MS
(ESI) m/z¼380.2 (Mþþ1, 100); HRMS (ESI) calcd for C22H21NO3S
(Mþ): 379.1320; found: 379.1326.
4.4.1. Methyl 2-(2-isopropyl-12H-thiochromeno[2,3-b]quinolin-12-yl)
acrylate (4a). White solid; mp 114.5e115.3 ꢀC (n-hexane/EtOAc);
Rf¼0.68 (n-hexane/EtOAc, 16:1); IR (KBr): 1707 (CO2CH3) cmꢂ1; 1H
4.3.15. Methyl
methyl)acrylate (3o). Colorless oil; Rf¼0.52 (n-hexane/EtOAc, 2:1);
IR (neat): 3435 (OH), 1721 (CO2CH3) cmꢂ1 1H NMR (400 MHz,
CDCl3)
2-(hydroxy(7-methyl-2-(p-tolylthio)quinolin-3-yl)
;
NMR (400 MHz, CDCl3)
d
¼8.20 (1H, s, ArH), 7.97 (1H, d, J¼8.0 Hz,
d
¼8.11 (1H, s, ArH), 7.62 (1H, d, J¼8.4 Hz, ArH), 7.53 (1H, s,
ArH), 7.77 (1H, d, J¼8.0 Hz, ArH), 7.63e7.67 (1H, m, ArH), 7.44 (1H, t,
J¼7.6 Hz, ArH), 7.34 (1H, d, J¼8.0 Hz, ArH), 7.24 (1H, s, ArH), 7.11
(1H, dd, J¼8.0, 1.6 Hz, ArH), 6.17 (1H, s, ]CHH), 5.54 (1H, s, ]CHH),
5.31 (1H, s, CH), 3.70 (3H, s, OCH3), 2.85e2.95 (1H, m, CH(CH3)2),
1.25 (6H, d, J¼6.8 Hz, CH(CH3)2); 13C NMR (100 MHz, CDCl3)
ArH), 7.43 (2H, d, J¼8.4 Hz, ArH), 7.24 (1H, dd, J¼8.0, 1.6 Hz, ArH),
7.18 (2H, d, J¼8.0 Hz, ArH), 6.41 (1H, s, ]CHH), 6.11 (1H, s, ]CHH),
5.70 (1H,s, CHOH), 3.78 (3H, s, OCH3), 3.41 (1H, s, OH), 2.45 (3H, s,
CH3), 2.39 (3H, s, CH3); 13C NMR (100 MHz, CDCl3)
d
¼166.7, 157.0,
147.6, 140.4, 139.8, 138.2, 134.3 (2C), 133.5, 131.8, 129.5 (2C), 128.9,
127.5, 127.3, 127.24, 127.17, 124.2, 68.7, 52.3, 21.8, 21.4; MS (ESI) m/
z¼380.2 (Mþþ1, 100); HRMS (ESI) calcd for C22H21NO3S (Mþ):
379.1320; found: 379.1327.
d
¼166.5, 157.1, 148.4, 146.6, 137.6, 136.4, 132.4, 131.0, 129.7, 129.5,
128.3, 127.7, 127.5, 126.9, 126.5, 125.8, 125.4, 125.2, 52.1, 47.9, 33.8,
24.0, 23.9; MS (ESI) m/z¼376.3 (Mþþ1, 100); HRMS (ESI) calcd for
C23H21NO2S (Mþ): 375.1304; found: 375.1311.
4.3.16. Methyl 2-((2-(2,4-dichlorophenylthio)-5,7-dimethylquinolin-
4.4.2. Ethyl 2-(2-isopropyl-12H-thiochromeno[2,3-b]quinolin-12-yl)
3-yl)(hydroxy)methyl)acrylate (3p). Yellow oil; Rf¼0.53 (n-hexane/
acrylate (4b). White solid; mp 122.0e122.9 ꢀC (n-hexane/EtOAc);
EtOAc, 2:1); IR (neat): 3434 (OH), 1723 (CO2CH3) cmꢂ1
;
1H NMR
Rf¼0.68 (n-hexane/EtOAc, 16:1); IR (KBr): 1708 (CO2Et) cmꢂ1
;
1H
(400 MHz, CDCl3)
d
¼8.31 (1H, s, ArH), 7.47 (2H, dd, J¼5.2, 2.8 Hz,
NMR (400 MHz, CDCl3)
d
¼8.21 (1H, s, ArH), 7.97 (1H, d, J¼8.0 Hz,
ArH), 7.35 (1H, s, ArH), 7.23 (1H, d, J¼9.2 Hz, ArH), 7.11 (1H, s, ArH),
6.40 (1H, s, ]CHH), 6.11 (1H, s, ]CHH), 5.67 (1H, s, CHOH), 3.79
(3H, s, OCH3), 3.61 (1H, s, OH), 2.60 (3H, s, CH3), 2.42 (3H, s, CH3);
ArH), 7.76 (1H, d, J¼8.0 Hz, ArH), 7.65 (1H, t, J¼8.0 Hz, ArH), 7.44
(1H, t, J¼8.0 Hz, ArH), 7.34 (1H, d, J¼8.0 Hz, ArH), 7.30 (1H, d,
J¼1.6 Hz, ArH), 7.11 (1H, dd, J¼8.0, 1.6 Hz, ArH), 6.17 (1H, s, ]CHH),
5.54 (1H, s, ]CHH), 5.29 (1H, s, CH), 4.08e4.22 (2H, m, OCH2CH3),
2.85e2.95 (1H, m, CH(CH3)2), 1.22e1.26 (9H, m, OCH2CH3, and CH
13C NMR (100 MHz, CDCl3)
d
¼166.7, 154.3, 148.0, 140.4, 139.8,
138.7, 136.7, 134.8, 134.3, 131.4, 130.7, 129.6, 129.5, 129.1, 127.6,
127.2, 125.5, 123.8, 69.0, 52.3, 21.8, 18.7; MS (ESI) m/z¼448.2
(CH3)2); 13C NMR (100 MHz, CDCl3)
d
¼166.4, 157.5, 148.7, 146.9,

3516
W. Zhong et al. / Tetrahedron 67 (2011) 3509e3518
138.2, 136.7, 132.7,131.4, 130.1,129.8, 128.7,128.0, 127.8,127.2, 126.5,
126.1, 125.7, 125.5, 61.4, 48.2, 34.2, 24.30, 24.26, 14.6; MS (ESI) m/
z¼390.4 (Mþþ1, 100); HRMS (ESI) calcd for C24H23NO2S (Mþ):
389.1528; found: 389.1541.
7.12 (1H, dd, J¼8.0, 1.6 Hz, ArH), 6.18 (1H, s, ]CHH), 5.53 (1H, s, ]
CHH), 5.31 (1H, s, CH), 3.70 (3H, s, OCH3), 2.90 (1H, m, CH(CH3)2),
1.25 (6H, d, J¼6.8 Hz, CH(CH3)2); 13C NMR (100 MHz, CDCl3)
d
¼166.1, 157.2, 148.2, 144.6, 137.0, 135.1, 131.8, 131.0, 130.5, 130.3,
129.2, 129.0, 127.1, 126.5, 125.8, 125.2, 125.0, 124.9, 51.8, 47.5, 33.5,
23.6 (2C); MS (EI) m/z¼409 (Mþ, 68), 366 (42), 349 (47), 326 (38),
324 (100), 308 (55); HRMS (EI) calcd for C23H20ClNO2S (Mþ):
409.0932; found: 409.0926.
4.4.3. Butyl 2-(2-isopropyl-12H-thiochromeno[2,3-b]quinolin-12-yl)
acrylate (4c). Yellow oil; Rf¼0.64 (n-hexane/EtOAc, 16:1); IR (neat):
1712 (CO2Bu-n) cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d¼8.20 (1H, s,
ArH), 7.97 (1H, d, J¼8.0 Hz, ArH), 7.76 (1H, d, J¼8.0 Hz, ArH), 7.65
(1H, t, J¼8.0 Hz, ArH), 7.44 (1H, t, J¼8.0 Hz, ArH), 7.33 (1H, d,
J¼8.0 Hz, ArH), 7.30 (1H, d, J¼2.0 Hz, ArH), 7.11 (1H, dd, J¼8.0,
1.6 Hz, ArH), 6.15 (1H, s, ]CHH), 5.54 (1H, s, ]CHH), 5.30 (1H, s,
CH), 4.04e4.15 (2H, m, OCH2CH2CH2CH3), 2.85e2.95 (1H, m, CH
(CH3)2), 1.54e1.61 (2H, m, OCH2CH2CH2CH3), 1.24e1.33 (8H, m,
OCH2CH2CH2CH3, and CH(CH3)2), 0.86 (3H, t, J¼7.2 Hz,
4.4.8. Methyl 2-(3-methyl-12H-thiochromeno[2,3-b]quinolin-12-yl)
acrylate (4h) and methyl 2-(1-methyl-12H-thiochromeno[2,3-b]qui-
nolin-12-yl)acrylate (4h0). Yellow oil; Rf¼0.68 (n-hexane/EtOAc,
16:1); IR (neat): 1716 (CO2CH3) cmꢂ1 1H NMR (400 MHz, CDCl3)
;
d
¼8.21e8.34 (1H, m, ArH), 7.96e8.00 (1H, m, ArH), 7.76e7.79 (1H,
m, ArH), 7.63e7.65 (1H, m, ArH), 7.42e7.46 (1H, m, ArH), 7.04e7.35
(3H, m, ArH), 6.16e6.17 (1H, m, ]CHH), 5.53e5.80 (1H, m, ]CHH),
5.29e5.40 (1H, m, CH), 3.69 (3H, s, OCH3), 2.48 (1.0H, s, CH3, 4h0),
2.40 (0.4H, s, CH3, 4h0), 2.34 (1.5H, s, CH3, 4 h); 13C NMR (100 MHz,
OCH2CH2CH2CH3); 13C NMR (100 MHz, CDCl3)
d
¼166.2, 157.1, 148.4,
146.5,138.0,136.4,132.3,131.1,129.7,129.5,128.4,127.7,127.5,126.9,
126.1, 125.8, 125.3, 125.1, 64.9, 47.9, 33.8, 30.6, 24.0, 23.9, 19.2, 13.8;
MS (ESI) m/z¼418.3 (Mþþ1, 100); HRMS (ESI) calcd for C26H27NO2S
(Mþ): 417.1826; 417.1819.
CDCl3)
d
¼166.5, 157.1, 156.8, 146.7, 146.5, 137.4, 136.9, 136.5, 136.4,
135.4, 133.7, 133.4, 130.2, 129.8, 129.4, 129.2, 128.9, 128.8, 128.4,
128.10,128.06,127.9,127.7,127.6,127.5 (2C),127.3,127.2,127.1,127.0,
126.9, 126.6, 126.5, 126.4, 125.83, 125.76, 125.7, 125.1, 52.1, 48.6,
48.2, 47.8, 44.1, 20.1, 20.4, 20.0; MS (ESI) m/z¼348.3 (Mþþ1, 100);
HRMS (ESI) calcd for C21H17NO2S (Mþ): 347.1062; found: 347.1051.
4.4.4. Methyl 2-(4-methyl-12H-thiochromeno[2,3-b]quinolin-12-yl)
acrylate (4d). White solid; mp 140.4e141.3 ꢀC (n-hexane/EtOAc);
Rf¼0.66 (n-hexane/EtOAc, 16:1); IR (KBr): 1712 (CO2CH3) cmꢂ1; 1H
NMR (400 MHz, CDCl3)
d
¼8.34 (1H, s, ArH), 7.94 (1H, d, J¼8.0 Hz,
ArH), 7.78 (1H, d, J¼8.0 Hz, ArH), 7.61e7.66 (1H, m, ArH), 7.41e7.45
(1H, m, ArH), 7.32 (1H, d, J¼8.0 Hz, ArH), 7.17 (1H, t, J¼8.0 Hz, ArH),
7.11 (1H, d, J¼8.0 Hz, ArH), 6.14 (1H, s, ]CHH), 5.80 (1H, s, ]CHH),
5.40 (1H, s, CH), 3.70 (3H, s, OCH3), 2.40 (3H, s, CH3); 13C NMR
4.4.9. Methyl 2-(2-chloro-12H-thiochromeno[2,3-b]quinolin-12-yl)
acrylate (4i). Yellow oil; Rf¼0.61 (n-hexane/EtOAc, 16:1); IR (neat):
1718 (CO2CH3) mꢂ1; 1H NMR (400 MHz, CDCl3)
d¼8.21 (1H, s, ArH),
7.98 (1H, d, J¼8.0 Hz, ArH), 7.78 (1H, d, J¼8.0 Hz, ArH), 7.65e7.70
(1H, m, ArH), 7.45e7.49 (1H, m, ArH), 7.43 (1H, dd, J¼8.0, 2.0 Hz,
ArH), 7.37 (1H, d, J¼8.0 Hz, ArH), 7.22 (1H, dd, J¼8.0, 2.4 Hz, ArH),
6.18 (1H, s, ]CHH), 5.55 (1H, s, ]CHH), 5.29 (1H, s, CH), 3.70 (3H, s,
(100 MHz, CDCl3)
d
¼166.5, 156.7, 146.6, 136.9, 136.7, 136.2, 133.1,
133.0, 129.7, 128.9, 127.6 (2C), 127.5, 127.3, 126.9, 126.5, 125.6, 125.1,
52.1, 44.1, 20.0; MS (ESI) m/z¼348.2 (Mþþ1, 100); HRMS (ESI) calcd
for C21H17NO2S (Mþ): 347.1042; found: 347.1053.
OCH3); 13C NMR (100 MHz, CDCl3)
136.5, 134.6, 133.2, 132.0, 130.7, 130.0, 127.7, 127.6, 127.4, 127.0,
126.9, 126.7, 126.5, 126.0, 52.1, 47.6; MS (ESI) m/z (%)¼368.3 (Mþþ1,
100); HRMS (ESI) calcd for C20H14ClNO2S (Mþ): 367.0512; 367.0517.
d
¼166.2, 155.9, 146.6, 137.4,
4.4.5. Methyl 2-(12H-thiochromeno[2,3-b]quinolin-12-yl)acrylate
(4e). White solid; mp 153.1e153.7 ꢀC (n-hexane/EtOAc); Rf¼0.63
(n-hexane/EtOAc, 16:1); IR (KBr): 1712 (CO2CH3) cmꢂ1 1H NMR
;
(400 MHz, CDCl3)
d
¼8.22 (1H, s, ArH), 7.96 (1H, d, J¼8.0 Hz, ArH),
4.4.10. Methyl 2-(4-chloro-12H-thiochromeno[2,3-b]quinolin-12-yl)
7.77 (1H, d, J¼8.0 Hz, ArH), 7.63e7.67 (1H, m, ArH), 7.40e7.46
(3H, m, ArH), 7.23e7.28 (2H, m, ArH), 6.17 (1H, s, ]CHH), 5.57
(1H, s, ]CHH), 5.29 (1H, s, CH), 3.69 (3H, s, OCH3); 13C NMR
acrylate (4j). White solid; mp 162.4e163.3 ꢀC (n-hexane/EtOAc);
Rf¼0.62 (n-hexane/EtOAc, 16:1); IR (KBr): 1710 (CO2CH3) cmꢂ1
;
1H
NMR (400 MHz, CDCl3)
d
¼8.42 (1H, s, ArH), 7.95 (1H, d, J¼8.0 Hz,
(100 MHz, CDCl3)
d
¼166.4, 158.8, 146.7, 137.4, 136.5, 133.7, 132.8,
ArH), 7.81 (1H, d, J¼8.0 Hz, ArH), 7.64e7.68 (1H, m, ArH), 7.44e7.48
(1H, m, ArH), 7.38 (1H, dd, J¼8.0, 1.2 Hz, ArH), 7.33 (1H, dd, J¼8.0,
1.2 Hz, ArH), 7.22 (1H, t, J¼8.0 Hz, ArH), 6.18 (1H, s, ]CHH), 6.15
(1H, s, ]CHH), 5.39 (1H, s, CH), 3.72 (3H, s, OCH3); 13C NMR
129.8, 129.6, 128.0, 127.8, 127.5 (2C), 127.2, 127.0, 126.9, 126.5,
125.8, 52.1, 48.3; MS (ESI) m/z¼334.3 (Mþþ1, 100); HRMS (ESI)
calcd for C20H15NO2S (Mþ): 333.0813; found: 333.0809.
(100 MHz, CDCl3)
d
¼166.1, 155.8, 146.6, 137.4, 136.0, 135.4, 134.3,
4.4.6. Methyl 2-(2-isopropyl-9-methyl-12H-thiochromeno[2,3-b]qui-
132.3, 130.0, 128.4, 127.8, 127.7, 127.6, 127.0, 126.8, 126.4, 125.9,
125.7, 52.2, 44.7; MS (ESI) m/z¼368.3 (Mþþ1, 100); HRMS (ESI)
calcd for C20H14ClNO2S (Mþ): 367.0512; found: 367.0519.
nolin-12-yl)acrylate (4f). Yellow oil; Rf¼0.68 (n-hexane/EtOAc,
16:1); IR (neat): 1718 (CO2CH3) cmꢂ1 1H NMR (400 MHz, CDCl3)
;
d
¼8.11 (1H, s, ArH), 7.86 (1H, d, J¼8.4 Hz, ArH), 7.53 (1H, s, ArH),
7.48 (1H, dd, J¼8.4, 2.0 Hz, ArH), 7.33 (1H, d, J¼8.0 Hz, ArH), 7.29
(1H, d, J¼2.0 Hz, ArH), 7.10 (1H, dd, J¼8.0, 2.0 Hz, ArH), 6.15 (1H, s,
]CHH), 5.52 (1H, s, ]CHH), 5.30 (1H, s, CH), 3.69 (3H, s, OCH3),
2.84e2.90 (1H, m, CH(CH3)2), 2.50 (3H, s, CH3),1.24 (6H, d, J¼6.8 Hz,
4.4.11. Methyl 2-(2,4-dichloro-12H-thiochromeno[2,3-b]quinolin-12-
yl)acrylate (4l). White solid; mp 207.3e208.5 ꢀC (n-hexane/EtOAc);
Rf¼0.61 (n-hexane/EtOAc, 16:1); IR (KBr): 1713 (CO2CH3) cmꢂ1
;
1H
NMR (400 MHz, CDCl3)
d
¼8.41 (1H, s, ArH), 7.95 (1H, d, J¼8.0 Hz,
CH(CH3)2); 13C NMR (100 MHz, CDCl3)
d¼166.5, 156.0, 148.3, 145.3,
ArH), 7.81 (1H, d, J¼8.0 Hz, ArH), 7.65e7.69 (1H, m, ArH), 7.47 (1H, t,
J¼7.2 Hz, ArH), 7.39 (1H, d, J¼2.0 Hz, ArH), 7.34 (1H, d, J¼2.0 Hz,
ArH), 6.19 (1H, s, ]CHH), 6.09 (1H, s, ]CHH), 5.39 (1H, s, CH), 3.72
137.7,135.8,135.6,132.6, 132.0, 131.1,129.5, 128.3, 127.4, 127.0, 126.4,
126.3, 125.3, 125.2, 52.1, 48.0, 33.8, 24.0, 23.9, 21.7; MS (ESI) m/
z¼390.4 (Mþþ1, 100); HRMS (ESI) calcd for C24H23NO2S (Mþ):
389.1422; found: 389.1421.
(3H, s, OCH3); 13C NMR (100 MHz, CDCl3)
d
¼165.9, 154.9, 146.6,
137.6, 137.0, 136.0, 134.8, 133.6, 130.9, 130.2, 127.7, 127.6 (2C), 127.0,
126.5, 126.3, 126.2, 125.4, 52.2, 44.4; MS (ESI) m/z¼402.2 (Mþþ1,
100); HRMS (ESI) calcd for C20H13Cl2NO2S (Mþ): 401.0024; found:
367.0041.
4.4.7. Methyl 2-(9-chloro-2-isopropyl-12H-thiochromeno[2,3-b]qui-
nolin-12-yl)acrylate (4g). Yellow solid; mp 58.4e59.7 ꢀC (n-hexane/
EtOAc); Rf¼0.65 (n-hexane/EtOAc, 16:1); IR (KBr): 1717 (CO2CH3)
cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
¼8.14 (1H, s, ArH), 7.89 (1H, d,
4.4.12. Methyl 2-(2,7-dimethyl-12H-thiochromeno[2,3-b]quinolin-
J¼8.8 Hz, ArH), 7.50 (1H, d, J¼2.4 Hz, ArH), 7.57 (1H, dd, J¼8.8,
12-yl)acrylate (4n). Yellow oil; Rf¼0.62 (n-hexane/EtOAc, 16:1);
2.4 Hz, ArH), 7.32 (1H, d, J¼8.0 Hz, ArH), 7.30 (1H, d, J¼1.6 Hz, ArH),
IR (neat): 1718 (CO2CH3) cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
¼8.15

W. Zhong et al. / Tetrahedron 67 (2011) 3509e3518
3517
(1H, s, ArH), 7.60 (1H, d, J¼8.0 Hz, ArH), 7.48 (1H, d, J¼6.8 Hz,
(100 MHz, DMSO-d6)
d
¼166.1, 155.5, 146.7, 138.4, 138.1, 137.7, 137.0,
ArH), 7.34 (1H, d, J¼8.0 Hz, ArH), 7.30 (1H, d, J¼8.0 Hz, ArH), 7.25
(1H, s, ArH), 7.04 (1H, d, J¼8.0 Hz, ArH), 6.14 (1H, s, ]CHH), 5.52
(1H, s, ]CHH), 5.29 (1H, s, CH), 3.68 (3H, s, OCH3), 2.76 (3H, s,
134.7, 131.0, 130.8, 129.4, 128.7, 128.2, 127.9, 127.3, 126.5, 125.9, 125.7,
60.4, 52.4; MS (ESI) m/z¼498.2 (Mþꢂ1, 100); HRMS (ESI) calcd for
C20H15Cl2NO6S2 (Mþ): 498.9787; found: 498.9774.
CH3), 2.34 (3H, s, CH3); 13C NMR (100 MHz, CDCl3)
d
¼166.5, 155.8,
145.8, 137.8, 137.3, 136.6, 135.8, 132.8, 130.8, 129.8, 129.4, 127.8
(2C), 127.5, 126.9, 126.2, 125.6, 125.4, 52.1, 47.8, 21.1, 18.0; MS (ESI)
m/z¼362.2 (Mþþ1, 100); HRMS (ESI) calcd for C22H19NO2S (Mþ):
361.1215; found: 361.1226.
4.4.18. (E)-Methyl 1,3-dichloro-12-methyl-5H-benzo[7,8]thiocino[2,3-
b]quinoline-6-carboxylate sulfate (5m). White solid; mp 257 ꢀC
(decomposed) (EtOH); Rf¼0.58 (DCM/EtOH, 9:1); IR (KBr): 3447
(OH), 1716 (CO2CH3) cmꢂ1
;
1H NMR (400 MHz, DMSO-d6)
d¼8.65
(1H, s, ArH), 7.94 (1H, s, ArH), 7.87 (1H, d, J¼2.4 Hz, ArH), 7.78 (1H, d,
J¼8.0 Hz, ArH), 7.73 (1H, d, J¼8.0 Hz, ArH), 7.54 (1H, d, J¼8.0 Hz,
ArH), 7.42 (1H, t, J¼8.0 Hz, ArH), 4.61 (2H, s, CH2), 3.84 (3H, s, OCH3),
3.35 (2H, d, J¼2.4 Hz, OHꢁ2), 2.22 (3H, s, CH3); 13C NMR (100 MHz,
4.4.13. Methyl 2-(4H-thieno[30,20:5,6]thiopyrano[2,3-b]quinolin-4-
yl)acrylate (4o). White solid; mp 130.2e131.0 ꢀC (n-hexane/EtOAc);
Rf¼0.66 (n-hexane/EtOAc, 16:1); IR (KBr): 1717 (CO2CH3) cmꢂ1
;
1H
NMR (400 MHz, CDCl3)
d
¼8.15 (1H, s, ArH), 7.96 (1H, d, J¼8.0 Hz,
DMSO-d6)
d
¼166.1, 154.5, 145.4, 139.5, 138.5, 138.1, 136.6, 135.0,
ArH), 7.75 (1H, d, J¼8.0 Hz, ArH), 7.64e7.68 (1H, m, ArH), 7.43e7.47
(1H, m, ArH), 7.30 (1H, d, J¼5.2 Hz, ArH), 6.97 (1H, d, J¼5.2 Hz, ArH),
6.24 (1H, s, ]CHH), 5.74 (1H, s, ]CHH), 5.42 (1H, s, CH), 3.74 (3H, s,
134.6, 131.0, 130.8, 129.2, 128.7, 127.7, 126.6, 126.0, 125.4, 125.0, 60.4,
52.4, 16.4; MS (ESI) m/z¼512.1 (Mþꢂ1, 1); HRMS (ESI) calcd for
C21H17Cl2NO6S2 (Mþ): 512.9796; found: 512.9787.
OCH3); 13C NMR (100 MHz, CDCl3)
d 166.1, 156.1, 146.5, 139.1, 136.8,
130.1, 128.9, 127.6, 127.5, 126.8 (2C), 126.7, 126.6, 126.0, 125.5, 125.2,
52.3, 42.7; MS (ESI) m/z¼340.2 (Mþþ1, 100); HRMS (ESI) calcd for
C18H13NO2S2 (Mþ): 339.0474; found: 339.0481.
4.4.19. (E)-Methyl 3,12-dimethyl-5H-benzo[7,8]thiocino[2,3-b]quin-
oline-6-carboxylate sulfate (5n). White solid; mp 215 ꢀC(decom-
posed) (EtOH); Rf¼0.64 (DCM/EtOH, 9:1); IR (KBr): 3465 (OH), 1709
(CO2CH3) cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
d
¼8.59 (1H, s, ArH),
4.4.14. (E)-Methyl 3-chloro-5H-benzo[7,8]thiocino[2,3-b]quinoline-
6-carboxylate sulfate (5i). White solid; mp 242 ꢀC(decomposed)
(EtOH); Rf¼0.56 (DCM/EtOH, 9:1); IR (KBr): 3464 (OH), 1712
7.96 (1H, s, ArH), 7.71 (1H, d, J¼8.0 Hz, ArH), 7.51 (2H, d, J¼8.0 Hz,
ArH), 7.40 (1H, t, J¼7.6 Hz, ArH), 7.29 (2H, d, J¼8.0 Hz, ArH), 4.61
(2H, s, CH2), 3.83 (3H, s, OCH3), 3.35 (2H, s, OHꢁ2), 2.38(3H, s, CH3),
(CO2CH3) cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
d
¼8.65 (1H, s, ArH),
2.28 (3H, s, CH3); 13C NMR (100 MHz, DMSO-d6)
d
¼166.2, 156.5,
7.94 (1H, s, ArH), 7.89 (1H, d, J¼7.2 Hz, ArH), 7.68e7.72 (1H, m, ArH),
145.5, 138.5, 137.8, 137.1, 134.9 (2C), 134.7, 130.6, 130.4, 129.4 (2C),
126.5, 125.7, 125.5, 125.3, 125.0, 60.4, 52.3, 20.9, 16.6; MS (ESI) m/
z¼458.1 (Mþꢂ1, 100); HRMS (ESI) calcd for C22H21NO6S2 (Mþ):
459.0732; found: 459.0717.
7.63 (1H, d, J¼8.0 Hz, ArH), 7.57e7.61 (2H, m, ArH), 7.50e7.54 (2H,
m, ArH), 4.56 (2H, s, CH2), 3.82 (3H, s, OCH3), 3.35 (2H, s, OHꢁ2); 13
C
NMR (100 MHz, DMSO-d6)
d
¼166.1, 156.5, 146.6, 137.8, 137.1, 135.8
(2C), 133.6, 130.8, 130.7, 128.9 (2C), 128.6, 128.4, 127.1, 126.2, 125.8,
125.6, 60.3, 52.2; MS (ESI) m/z¼464.2 (Mþꢂ1, 100); HRMS (ESI)
calcd for C20H16ClNO6S2 (Mþ): 465.0118; found: 465.0129.
Acknowledgements
We thank the National Key Technology R&D Program [No:
2007BAI34B00] and National Natural Science Foundation of China
[21076194] for financial support.
4.4.15. (E)-Methyl 1-chloro-5H-benzo[7,8]thiocino[2,3-b]quinoline-
6-carboxylate sulfate (5j). White solid; mp 223 ꢀC(decomposed)
(EtOH); Rf¼0.54 (DCM/EtOH, 9:1); IR (KBr): 3463 (OH), 1713
(CO2CH3) cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
d¼8.68 (1H, s, ArH),
Supplementary data
7.94 (1H, s, ArH), 7.91 (1H, d, J¼8.0 Hz, ArH), 7.69e7.73 (1H, m, ArH),
7.63 (2H, dd, J¼8.0, 1.6 Hz, ArH), 7.55e7.59 (1H, m, ArH), 7.48 (1H, t,
J¼7.6 Hz, ArH), 7.39 (1H, t, J¼7.6 Hz, ArH), 4.55 (2H, s, CH2), 3.82
(3H, s, OCH3), 3.36 (2H, s, OHꢁ2); 13C NMR (100 MHz, DMSO-d6)
Supplementary data associated with this article can be found in
online version at doi:10.1016/j.tet.2011.03.039.
d
¼166.1, 156.0, 146.8, 138.1, 137.4, 137.2, 136.5, 131.0, 130.8, 130.5,
References and notes
129.8, 129.0, 128.7, 127.7, 127.3, 126.4, 126.1, 125.7, 60.4, 52.4; MS
(ESI) m/z¼464.1 (Mþꢂ1, 100); HRMS (ESI) calcd for C20H16ClNO6S2
(Mþ): 465.0118; found: 367.0131.
1. (a) Vashist, U.; Carvalhaes, R.; D’agosto, M.; Silva, A. D. Chem. Biol. Drug Des.
2009, 74, 434e437; (b) Natarajan, J. K.; Alumasa, J. N.; Yearick, K.; Ekoue-Kovi,
K. A.; Casabianca, L. B.; Dios, A. C.; Wolf, C.; Roepe, P. D. J. Med. Chem. 2008, 51,
3466e3479.
2. Kategaonkar, A. H.; Pokalwar, R. U.; Sonar, S. S.; Gawali, V. U.; Shingate, B. B.;
Shingare, M. S. Eur. J. Med. Chem. 2010, 45, 1128e1132.
3. (a) Beauchard, A.; Jaunet, A.; Murillo, L.; Baldeyrou, B.; Lansiaux, A.; Cherouv-
rier, J. R.; Domon, L.; Picot, L.; Bailly, C.; Besson, T.; Thiery, V. Eur. J. Med. Chem.
2009, 44, 3858e3865; (b) Bolognese, A.; Correale, G.; Manfra, M.; Esposito, A.;
Novellino, E.; Lavecchia, A. J. Med. Chem. 2008, 51, 8148e8157.
4. Mulchin, B. J.; Newton, C. G.; Baty, J. W.; Grasso, C. H.; Martin, W. J.; Walton, M.
C.; Dangerfield, E. M.; Plunkett, C. H.; Berridge, M. V.; Harper, J. L.; Timmer, M.
S. M.; Stocker, B. L. Bioorg. Med. Chem. 2010, 18, 3238e3251.
4.4.16. (E)-Methyl 3-bromo-5H-benzo[7,8]thiocino[2,3-b]quinoline-
6-carboxylate sulfate (5k). White solid; mp 235 ꢀC(decomposed)
(EtOH); Rf¼0.51 (DCM/EtOH, 9:1); IR (KBr): 3458 (OH), 1712
(CO2CH3) cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
d¼8.65 (1H, s, ArH),
7.94 (1H, s, ArH), 7.90 (1H, d, J¼8.0 Hz, ArH), 7.69e7.73 (1H, m, ArH),
7.64e7.66 (2H, m, ArH), 7.51e7.58 (3H, m, ArH), 4.56 (2H, s, CH2),
3.82 (3H, s, OCH3), 3.34 (2H, s, OHꢁ2); 13C NMR (100 MHz, DMSO-
d6)
d
¼166.1, 156.5, 146.6, 137.9, 137.3, 136.1 (2C), 131.9 (2C), 130.9,
5. (a) Lu, C. M.; Chen, Y. L.; Chen, H. L.; Chen, C. A.; Lu, P. J.; Yang, C. N.; Tzeng, C. C.
Bioorg. Med. Chem. 2010, 18, 1948e1957; (b) Tseng, C. H.; Chen, Y. L.; Chung, K. Y.;
Cheng, C. M.; Wang, C. H.; Tzeng, C. C. Bioorg. Med. Chem. 2009, 17, 7465e7476.
6. Zemtsova, M. N.; Zimichev, A. V.; Trakhtenberg, P. L.; Belen’kaya, R. S.; Boreko,
E. I. Pharm. Chem. J. 2008, 42, 571e573.
130.6, 129.0, 128.7, 127.2, 126.3, 125.8, 125.6, 122.3, 60.4, 52.4; MS
(ESI) m/z¼508.1 (Mþꢂ1, 100); HRMS (ESI) calcd for C20H16BrNO6S2
(Mþ): 508.9689; found: 508.9672.
7. Lesage, A. S. J.; Bischoff, F. P.; Janseen, C. G. M.; Lavreysen, H. WO 03082350, 2003.
8. Prakash Naik, H. R.; Bhojya Naik, H. S.; Ravikumar Naik, T. R.; Bindu, P. J.; Raja
Naika, H.; Aravinda, T.; Lamani, D. S. Med. Chem. 2009, 5, 148e157.
9. (a) Lin, X.-F.; Cui, S.-L.; Wang, Y.-G. Tetrahedron Lett. 2006, 47, 3127e3130; (b)
Sakai, N.; Annaka, K.; Konakahara, T. J. Org. Chem. 2006, 71, 3653e3655; (c)
Kohn, L. K.; Pavam, C. H.; Veronese, D.; Coelho, F.; De Carvalho, J. E.; Almeida,
W. P. Eur. J. Med. Chem. 2006, 41, 738e744; (d) Singh, V.; Hutait, S.; Batra, S. Eur.
J. Org. Chem. 2009, 3454e3466.
4.4.17. (E)-Methyl 1,3-dichloro-5H-benzo[7,8]thiocino[2,3-b]quino-
line-6-carboxylate sulfate (5l). White solid; mp 246 ꢀC(decomposed)
(EtOH); Rf¼0.52 (DCM/EtOH, 9:1); IR (KBr): 3458 (OH),1710 (CO2CH3)
cmꢂ1; 1H NMR (400 MHz, DMSO-d6)
d
¼8.68 (1H, s, ArH), 7.91 (2H, m,
ArH), 7.84 (1H, d, J¼2.4 Hz, ArH), 7.68 (1H, d, J¼8.4 Hz, ArH), 7.62 (1H,
d, J¼8.4 Hz, ArH), 7.57e7.59 (1H, m, ArH), 7.50 (1H, dd, J¼8.4, 2.4 Hz,
ArH), 4.57 (2H, s, CH2), 3.82(3H, s, OCH3), 3.35 (2H, s, OHꢁ2); 13C NMR
10. (a) Ma, G.-N.; Jiang, J.-J.; Shi, M.; Wei, Y. Chem. Commun. 2009, 37, 5496e5514;
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