Reactions of 2-(trifluoromethyl)-2-hydroxy-2H-chromenes with thiophenols promoted by Lewis acid

Article abstract of DOI:10.1016/j.tet.2012.06.101

A Lewis acid promoted nucleophilic substitution reaction between 2-(trifluoromethyl)-2-hydroxy-3-ethoxycarbonyl-2H-chromenes 1 and thiophenols affording thiophenyl substituted products, that is, 4-thiophenyl-2- trifluoromethyl-3-ethoxycarbonyl-4H-chromene and 2-thiophenyl-2-trifluoromethyl- 3-ethoxycarbonyl-2H-chromene.

Full text of DOI:10.1016/j.tet.2012.06.101

Tetrahedron 68 (2012) 8011e8017
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Tetrahedron
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Reactions of 2-(trifluoromethyl)-2-hydroxy-2H-chromenes with thiophenols
promoted by Lewis acid
,
,
a
,
b
a
b,
*
Xinjin Li a b, Jingwei Zhao b , Zhongwei Wang , Jianwei Han , Jian Zhao , Shizheng Zhu
*
*
a College of Material Science and Technology, Shandong University of Science and Technology, Qingdao, Shandong 266590, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 19 April 2012
Received in revised form 14 June 2012
Accepted 26 June 2012
Available online 6 July 2012
A Lewis acid promoted nucleophilic substitution reaction between 2-(trifluoromethyl)-2-hydroxy-
3-ethoxycarbonyl-2H-chromenes 1 and thiophenols affording thiophenyl substituted products, that is,
4-thiophenyl-2-trifluoromethyl-3-ethoxycarbonyl-4H-chromene and 2-thiophenyl-2-trifluoromethyl-
3-ethoxycarbonyl-2H-chromene.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Chromene
Trifluoromethyl
Thiophenol
Nucleophilic substitution
Lewis acid
1. Introduction
recently, Wu group synthesized substituted 2H-chromenes through
direct FriedeleCrafts reactions of chromene hemiacetals with
Chromenes as a major class of naturally occurring compounds
have been studied widely because of their usefulness as biologically
active agents.1 Among various chromene isomers, 2H-chromenes
and 4H-chromenes are attracting much more interests from chem-
ists due to their wide application in biological and material fields.
Many of them were used as the substrates for the synthesis of anti-
HIV,2 antitumor,3 cytotoxic agent,4 antimicrobial,5 fungicidal,6 and
were also applied in photosensitizers, fluorescent and laser dyes.7
During the past few decades, many studies have been reported on
the synthesis of the 4H-chromene8 and 2H-chromene9 ring system.
Generally, chromenes were synthesized by three-component10
condensation involving a phenol, an aromatic aldehyde, and malo-
nonitrile.11 However, most of these methods suffered from several
drawbacks, including low yields, long steps, and poor substrate
tolerability. Recently, Wulff group developed a facile route to build
chromene ring structure through a cascade reaction12 and got
2H-chromenes that only contain two methyl substituted groups and
without other substituted group in the chromene ring. In addition, it
is proved to be an efficient process for introducing functional groups
to chromene ring especial for 2-hydroxy-2H-chromenes. Laurent
reported the synthesis of substituted 2-perfluoroalkyl-4H-chro-
menes with high yields in the presence of SnCl4 (Scheme 1).13 More
indoles catalyzed by Hf(OTf)4 (Scheme 2).14
It is well known that introducing fluorine atom into organic
compounds is one of the major strategies for the modification or
enhancement of their biological activities. But to our best knowl-
edge, there are few reports on the synthesis of both thiophenol
and trifluoromethyl substituted chromenes.15 In our group,
we have recently reported a Lewis acid promoted reactions of
2-(trifluoromethyl)-2-hydroxy-2H-chromenes 1 with indoles and
isolated a series of 2-substituted chromenes or 4-substituted
chromenes (Scheme 3).16
In order to expand the chromene library, herein we report a new
reaction of 2-(trifluoromethyl)-2-hydroxy-2H-chromenes 1 with
thiophenols 2 affording a series of substituted 2-trifluoromethyl-
2H-chromenes and 4H-chromenes.
2. Results and discussion
Considering the hemiketal and allylic structure in 2-(tri-
fluoromethyl)-2-hydroxy-3-ethoxycarbonyl-2H-chromene 1, it is
anticipated that nucleophilic substitution reaction would take place
at 2-position or 4-position of 1, affording corresponding 2H-chro-
menes or 4H-chromenes. We have got very good results when in-
doles were employed as nucleophiles. In order to explore the
reactivity of 1, thiophenol was chosen as a nucleophile to optimize
reaction conditions (Table 1). It was not surprised that no reaction
* Corresponding authors. E-mail address: zhusz@mail.sioc.ac.cn (S. Zhu).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.06.101

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X. Li et al. / Tetrahedron 68 (2012) 8011e8017
Scheme 1.
Scheme 2.
Scheme 3.
took place without Lewis acids (Table 1, entries 1 and 2). After
different Lewis acids were examined, AlCl3 provided the best result.
The products 3aa and 4aa were obtained in a total yield of 83% and
isolated with a ratio of 1.5 (Table 1, entry 5). In addition, a stoi-
chiometric Lewis acid is necessary because when 10% or 50% AlCl3
was employed, only a yield of 5% or 35% was observed (Table 1,
entries 3 and 4). However, poor isolated yields were obtained when
other Lewis acids such as SnCl4 and ZnCl2 were utilized (Table 1,
entries 7e9). Though good regioselectivity and yields were ob-
served in the reaction of 1 and indoles promoted by BF3$OEt2 in our
Table 1
Reactions of 1a with thiophenol under different conditions
Entry
Lewis acid (mol %)
Solvent
Time (h)
Temp
Ratioa
Total yieldb (%)
1
2
3
4
5
6
7
8
d
CH2Cl2
CH3CN
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH3CN
THF
24
12
12
9
8
11
4
9
9
11
9
rt
Reflux
d
Trace
d
5
35
83
61
6
7
7
75
d
d
d
AlCl3 (10)
AlCl3 (50)
AlCl3 (100)
BF3$OEt2 (100)
SnCl4 (100)
SnCl4 (100)
ZnCl2 (100)
AlCl3 (100)
AlCl3 (100)
0 ꢀC to rt
0 ꢀC to rt
0 ꢀC to rt
0 ꢀC to rt
ꢁ78 ꢀC to rt
ꢁ78 ꢀC to rt
0 ꢀC to rt
0 ꢀC to rt
0 ꢀC to rt
d
1.5
1.5
1.4
1.7
1.7
1.2
1.5
d
9
10
11
a
The mass ratio of product 3aa to 4aa.
Isolated yields.
b

X. Li et al. / Tetrahedron 68 (2012) 8011e8017
8013
previous study, only a moderate yield was reached in the reaction
of 1a with 2a. (Table 1, entry 6). Other aprotic solvents such
as CH3CN and THF were also examined in this reaction (Table 1,
entries 10 and 11).
decreased the reactivity of 2d (Table 2, entry 3). In comparison with
results of thiophenol, not too much change was found in yield and
ratio when a substituent such as Cl and Br was introduced into 1a.
The desired both 4H-chromenes and 2H-chromenes products were
obtained in a good yield for 2b (Table 2, entries 5 and 9) and a low
yield for 2d (Table 2, entries 7 and 10). If the reaction occurred
between 1d and 2, it was interesting that BF3$OEt2 promoted this
reaction more effectively than AlCl3, but longer reaction time was
necessary and moderate yields of 54e75% were observed (Table 2,
entries 11 and 12).
Further experiments demonstrated that thiophenol derivatives
could also react with 1 under the optimized condition. The results
obtained were summarized in Table 2. When reaction occurred
between 1a and 2b, which contains an electron-donating func-
tional group CH3, corresponding additional products 4H-chromene
and 2H-chromene were obtained in a good total yield of 87% and
isolated with a ratio of 1.5 (Table 2, entry 2). Once a nitro group was
introduced into to 2, longer reaction time was required and a lower
total yield of 43% was observed that was attributed to the strong
electron withdrawing character of the nitro group, which greatly
All new compounds were identified by 1H, 13C, and 19F NMR
spectroscopy and mass spectrometry. As shown in Fig. 1, the
structure of compound 3bc was also confirmed by X-ray crystal-
lography. It was noted that the congested 4-substituted thiophenyl
Table 2
Reactions of 1 with 2 promoted by Lewis acid in CH2Cl2 at room temperature
Entry
1
2
Lewis acid
(100 mol %)
Time
(h)
Products and yielda
(%)
Ratiob
Total yielda
(%)
1
2
3
4
5
6
7
8
1a
1a
1a
1b
1b
1b
1b
1c
1c
1c
1d
1d
1d
2a
2b
2d
2a
2b
2c
2d
2a
2b
2d
2a
2b
2d
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
AlCl3
BF3$OEt2
BF3$OEt2
BF3$OEt2
8
6
18
8
6
6
18
8
6
18
13
10
22
3aa (50)
3ab (52)
3ad (30)
3ba (52)
3bb (53)
3bc (52)
3bd (35)
3ca (54)
3cb (54)
3cd(36)
3da (32)
3db (41)
3dd (25)
4aa (33)
4ab (35)
4ad (13)
4ba (34)
4bb (36)
4bc (34)
4bd (10)
4ca (33)
4cb (36)
4cd (11)
4da (22)
4db (34)
4dd (10)
1.5
1.5
2.3
1.5
1.5
1.5
3.5
1.6
1.5
3.3
1.5
1.2
2.5
83
87
43
86
89
86
45
87
90
47
54
75
35
9
10
11
12
13
a
Isolated yields.
The mass ratio of product 3 to 4.
b
Fig. 1. The structure of compound 3bc.

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X. Li et al. / Tetrahedron 68 (2012) 8011e8017
almost located at upside of the whole chromene ring and the angle
of C7eSeC14 is 100.9ꢀ.
However, the chromene ring of 1 also could be opened in the
presence of AlCl3 and produces intermediate E, which is then
attacked by thiophenols to afford products 3 (b2) and 4 (b1). To gain
further understanding of the mechanism, a comparative experi-
ment was performed and the reaction process was monitored by
19F NMR. Compared to the normal reaction between 1a and 2a
(Fig. 2, a), experiment b was carried out in the absence of nucleo-
philic reagent 2a. If the chromene ring was opened in the presence
of AlCl3, there would be another fluorine signal (CF3eC]O) dif-
ferent from the signal of 1a (ꢁ87.32 ppm). Obviously, only a signal
was found and matched the diagnostic signal of 1a (Fig. 2, b).
According to the collected evidence, path b seems to be un-
reasonable. The above results indicate that the AlCl3 firstly react
with the hydroxy group of 1 rather than lead the chromene ring
opening.
A reaction mechanism of 2-(trifluoromethyl)-2-hydroxy-2H-
chromenes 1 with thiophenols promoted by AlCl3 has been
proposed on the basis of previous investigations14,15 (Scheme 4,
path a). Initially, the hydroxy group of 1 is activated by AlCl3 to
form intermediate A. Subsequently, an elimination of AlCl2Oꢁ
produces the oxonium intermediate B, which is attacked by
thiophenols to form product 4. Because of the electron de-
localization of oxonium intermediate, intermediate C is formed
and followed by the attack of
2 to produce substituted
4H-chromene 3. It is noted that the attack prefer to take place at
4-position rather than at 2-position due to the steric hindrance
of CF3 group, which can explain why 4H-chromene 3 is the
major product.
Scheme 4. Possible mechanisms for the formation of chromenes 3 and 4.
Fig. 2. 19F NMR spectra of experiments a and b after 6 h.

X. Li et al. / Tetrahedron 68 (2012) 8011e8017
8015
3. Conclusion
691 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d
1.36 (t, J¼7.2 Hz, 3H), 4.30
(q, J¼7.2 Hz, 2H), 6.91 (d, J¼8.1 Hz, 1H), 7.02 (t, J¼7.5 Hz, 1H), 7.17 (d,
In summary, the reaction of 2-(trifluoromethyl)-2-hydroxy-2H-
J¼7.5 Hz, 1H), 7.24e7.40 (m, 3H), 7.52 (d, J¼7.5 Hz, 2H), 7.60 (s, 1H).
2
chromenes
1
with thiophenols
2
promoted by AlCl3 was
13C NMR (100 MHz, CDCl3):
d
14.1, 61.5, 91.0 (q, JCeF¼33 Hz, CF3),
studied, which gave two thiophenyl substituted products, that is,
4-thiophenyl-2-trifluoromethyl-3-ethoxycarbonyl-4H-chromene
and 2-thiophenyl-2-trifluoromethyl-3-ethoxycarbonyl-2H-chro-
mene. The reaction mechanism was also discussed. It was found
that AlCl3 firstly reacted with the hydroxy group of 1 and formed 4-
substituted chromene and 2-substituted chromene in the attack of
2. Further studies to expand the chromene library and on their
bioactivity are in progress and will be reported in the near future.
116.8, 118.8, 121.0, 123.0 (q, 1JCeF¼285 Hz, CF3), 123.2, 127.8, 128.5,
128.8, 130.0, 133.2, 137.1, 137.7, 151.0, 163.0. 19F NMR (282 MHz,
CDCl3):
d
70.44 (s, 3F, CF3). MS (ESI): m/z¼403.0 (MþNa)þ.
HRMS (ESI): m/z calcd for (C19H15F3O3SþNa)þ: 403.0592; found:
403.0592.
4.2.3. 2-(Trifluoromethyl)-3-ethoxycarbonyl-4-(phenylthio)-6-
chloro-4H-chromene (3ba). Yield 52%, yellow solid, mp 61e63 ꢀC. IR
(KBr): 1728, 1621, 1567, 1479, 1452, 1367, 1341, 1277, 1236, 1213,
4. Experimental
1170, 1007, 873, 819, 755, 691 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
d
1.41 (t, J¼7.2 Hz, 3H), 4.40 (q, J¼7.2 Hz, 2H), 5.21 (s, 1H), 6.66 (d,
4.1. General information
J¼8.7 Hz, 1H), 7.07e7.21 (m, 5H), 7.34(t, J¼7.5 Hz, 1H), 7.44 (s, 1H).
13C NMR (100 MHz, CDCl3):
d 13.9, 45.1, 62.2, 109.7, 117.4, 118.8 (q,
Commercial reagents were used without further purification. All
solvents used were dried and purified by distillation. The starting
chromenes 1aed were prepared according to described proced-
ure.9d Melting points were measured on a Temp-Melt apparatus
and uncorrected. 1H NMR and 19F NMR spectra were recorded on
a Bruker AM-300 instrument with Me4Si and CFCl3 as the internal
standards, respectively. 13C NMR spectra were recorded on a Bruker
AM-400 instrument with Me4Si as the internal standard. FTIR
spectra were obtained with a Nicolet AV-360 spectrophotometer.
Mass spectra were obtained on a Finnigan GCeMS 4021 or a Fin-
nigan MAT8430 instrument. Single crystal X-ray structure analysis
was performed on a Bruker P4 instrument. All reactions were
monitored by TLC or 19F NMR.
1JCeF¼273 Hz, CF3), 121.0, 128.4, 128.7, 128.8, 128.9, 129.9, 130.5,
137.2, 142.8 (q, JCeF¼38 Hz, CF3), 148.6, 164.2. 19F NMR (282 MHz,
2
CDCl3):
d
65.8 (s, 3F, CF3). MS (ESI): m/z¼437.0 (MþNa)þ. HRMS
(ESI): m/z calcd for (C19H14ClF3O3SþNa)þ: 437.0198; found:
437.0196.
4.2.4. 2-(Trifluoromethyl)-2-(phenylthio)-3-ethoxycarbonyl-6-
chloro-2H-chromene (4ba). Yield 34%, yellow solid, mp 64e66 ꢀC.
IR (KBr): 1729, 1629, 1560, 1477, 1440, 1369, 1277, 1234, 1215, 1200,
1124, 1010, 882, 820, 750, 691 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
d
1.28 (t, J¼6.9 Hz, 3H), 4.24 (q, J¼6.9 Hz, 2H), 6.78 (d, J¼9.0 Hz, 1H),
7.06 (s, 1H), 7.17e7.31 (m, 4H), 7.43e7.41 (m, 3H). 13C NMR
2
(100 MHz, CDCl3):
d
14.0, 61.8, 91.1 (q, JCeF¼33 Hz, CF3), 118.2,
120.0, 122.4, 122.8 (q, 1JCeF¼285 Hz, CF3), 127.4, 128.0, 128.1, 128.6,
4.2. Typical procedure for the reaction of 2-(trifluoromethyl)-
2-hydroxy-2H-chromene (1a) with thiophenol (2a) in the
presence of AlCl3 in CH2Cl2
130.1, 132.7, 135.6, 137.7, 149.4, 162.6. 19F NMR (282 MHz, CDCl3):
d
70.3 (s, 3F, CF3). MS (ESI): m/z¼437.0 (MþNa)þ. HRMS (ESI): m/z
calcd for (C19H14ClF3O3SþNa)þ: 437.0198; found: 437.0196.
To a stirred solution of chromene (1a, 288 mg, 1 mmol) and
anhydrous aluminum chloride (133 mg, 1 mmol) in anhydrous
dichloromethane (10 mL) under nitrogen was added thiophenol
(2a, 165 mg, 1.5 mmol) at 0 ꢀC. The mixture was stirred at this
temperature for 30 min and then warmed to room temperature. At
the end of the reaction (8 h) as judged by TLC or 19F NMR, the
mixture was diluted with water (10 mL), quenched with a solution
of sodium bicarbonate (10 mL), and extracted with dichloro-
methane (3ꢂ15 mL). The organic layers were washed with brine
(2ꢂ20 mL) and dried over sodium sulfate. The crude products were
obtained by removal of the solvent under reduced pressure and
were isolated by column chromatography using an eluent of ethyl
acetate/petroleum ether (1:20) to afford the desired chromenes 3aa
and 4aa.
4.2.5. 2-(Trifluoromethyl)-3-ethoxycarbonyl-4-(phenylthio)-6-
bromo-4H-chromene (3ca). Yield 54%, yellow solid, mp 66e68 ꢀC.
IR (KBr): 1719, 1667, 1478, 1439, 1373, 1358, 1295, 1243, 1224, 1185,
1155, 1121, 995, 811, 747, 694 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
d
1.41 (t, J¼7.2 Hz, 3H), 4.40 (q, J¼7.2 Hz, 2H), 5.20 (s, 1H), 6.60 (d,
J¼8.7 Hz,1H), 7.08 (d, J¼8.7 Hz, 2H), 7.18 (t, J¼6.9 Hz, 2H), 7.26e7.34
(m, 2H), 7.58 (s, 1H). 13C NMR (100 MHz, CDCl3):
d 13.9, 44.9, 62.2,
1
109.8, 117.7 117.8, 118.8 (q, JCeF¼273 Hz, CF3), 122.9, 128.4, 128.7,
129.9, 131.8, 137.2, 142.8 (q, 2JCeF¼39 Hz, CF3), 149.1, 164.2. 19F NMR
(282 MHz, CDCl3):
d
65.9 (s, 3F, CF3). MS (ESI): m/z¼481.0 (MþNa)þ.
HRMS (ESI): m/z calcd for (C19H14BrF3O3SþNa)þ: 480.9698; found:
480.9691.
4.2.6. 2-(Trifluoromethyl)-2-(phenylthio)-3-ethoxycarbonyl-6-
bromo-2H-chromene (4ca). Yield 33%, yellow solid, mp 68e70 ꢀC.
IR (KBr): 1731, 1623, 1565, 1477, 1367, 1339, 1257, 1234, 1213, 1171,
4.2.1. 2-(Trifluoromethyl)-3-ethoxycarbonyl-4-(phenylthio)-4H-
chromene (3aa). Yield 50%, white solid, mp 75e76 ꢀC. IR (KBr):
1718, 1674, 1586, 1488, 1462, 1375, 1298, 1242, 1222, 1193, 1150,
1027, 1006, 931, 872, 754, 690 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
d
1.35 (t, J¼7.2 Hz, 3H), 4.30 (q, J¼7.2 Hz, 2H), 6.80 (d, J¼9.0 Hz, 1H),
1092, 996, 766, 746, 695 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d
1.41 (t,
7.23e7.28 (m, 3H), 7.35 (d, J¼7.5 Hz, 1H), 7.41e7.50 (m, 4H). 13C
J¼7.2 Hz, 3H), 4.40 (q, J¼7.2 Hz, 2H), 5.28 (s, 1H), 6.72 (d, J¼7.8 Hz,
NMR (100 MHz, CDCl3):
d
14.0, 61.8, 91.1 (q, 2JCeF¼32 Hz, CF3), 115.2,
1H), 7.04 (d, J¼7.8 Hz, 2H), 7.12e7.21 (m, 4H), 7.30 (t, J¼7.2 Hz, 1H),
118.6, 120.6, 122.3, 122.8 (q, 1JCeF¼283 Hz, CF3), 127.4, 128.7, 130.1,
7.45 (d, J¼6.9 Hz, 1H, ArH). 13C NMR (100 MHz, CDCl3):
d
13.9, 45.5,
131.0, 135.5, 135.6, 137.7, 150.0, 162.6. 19F NMR (282 MHz, CDCl3):
1
62.1, 109.9, 116.0, 118.9 (q, JCeF¼273 Hz, CF3), 119.2, 125.7, 128.5,
d
70.4 (s, 3F, CF3). MS (ESI): m/z¼480.9 (MþNa)þ. HRMS (ESI): m/z
2
128.8, 128.9, 129.3, 129.6, 137.2, 143.0 (q, JCeF¼38 Hz, CF3), 150.2,
calcd for (C19H14BrF3O3SþNa)þ: 480.9698; found: 480.9691.
164.7. 19F NMR (282 MHz, CDCl3):
d 65.9 (s, 3F, CF3). MS (ESI): m/
z¼403.0 (MþNa)þ. HRMS (ESI): m/z calcd for (C19H15F3O3SþNa)þ:
4.2.7. 2-(Trifluoromethyl)-3-ethoxycarbonyl-4-(phenylthio)-6-nitro-
4H-chromene (3da). Yield 32%, yellow solid, mp 109e111 ꢀC. IR
(KBr): 1726, 1683, 1537, 1472, 1441, 1377, 1345, 1302, 1277, 1244,
403.0592; found: 403.0586.
4.2.2. 2-(Trifluoromethyl)-2-(phenylthio)-3-ethoxycarbonyl-2H-
chromene (4aa). Yield 33%, yellow oil. IR (KBr): 1731, 1609, 1558,
1488, 1457, 1369, 1291, 1236, 1218, 1171, 1024, 1009, 880, 749,
1192, 1155, 1080, 834, 744, 697 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
d
1.43 (t, J¼6.9 Hz, 3H), 4.43 (q, J¼6.9 Hz, 2H), 5.28 (s, 1H), 6.84 (d,
J¼9.0 Hz, 1H), 7.07 (d, J¼7.8 Hz, 2H), 7.19 (t, J¼7.5 Hz, 2H), 7.36

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X. Li et al. / Tetrahedron 68 (2012) 8011e8017
(t, J¼6.9 Hz, 1H), 8.06 (d, J¼6.6 Hz, 1H), 8.40 (s, 1H). 13C NMR
1H), 7.36 (d, J¼7.8 Hz, 2H), 7.49 (s, 1H). 13C NMR (100 MHz, CDCl3):
(100 MHz, CDCl3):
d
13.9, 44.6, 62.6, 110.8, 117.1, 118.6 (q,
d
14.0, 21.3, 61.7, 91.2 (q, 2JCeF¼33 Hz, CF3), 118.2, 120.1, 122.4, 122.8
1JCeF¼273 Hz, CF3), 120.8, 124.2, 125.5, 127.9, 129.0, 130.2, 137.1,
(q, 1JCeF¼285 Hz, CF3), 123.8, 127.9, 128.0, 129.4, 132.6, 135.5, 137.7,
2
142.2 (q, JCeF¼39 Hz, CF3), 145.1, 153.8, 163.8. 19F NMR (282 MHz,
140.6, 149.4, 162.6. 19F NMR (282 MHz, CDCl3):
d 71.0 (s, 3F, CF3). MS
CDCl3):
d
65.9 (s, 3F, CF3). MS (ESI): m/z¼448.0 (MþNa)þ. HRMS
(ESI): m/z¼451.0 (MþNa)þ. HRMS (ESI): m/z calcd for
(ESI): m/z calcd for (C19H14F3NO5SþH)þ: 426.0578; found:
(C20H16ClF3O3SþNa)þ: 451.0398; found: 451.0353.
426.0618.
4.2.13. 2-(Trifluoromethyl)-3-ethoxycarbonyl-4-(p-tolylthio)-6-
bromo-4H-chromene (3cb). Yield 54%, yellow solid, mp 93e95 ꢀC. IR
(KBr): 1716,1651,1570,1476,1358,1305,1277,1245,1193,1151,1120,
4.2.8. 2-(Trifluoromethyl)-2-(phenylthio)-3-ethoxycarbonyl-6-nitro-
2H-chromene (4da). Yield 22%, yellow solid, mp 74e76 ꢀC. IR (KBr):
1732, 1621, 1525, 1475, 1367, 1343, 1271, 1222, 1176, 1122, 1007, 924,
1095, 994, 861, 811, 785 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d 1.40 (t,
886, 745, 693 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d
1.36 (t, J¼7.2 Hz,
J¼7.2 Hz, 3H), 2.31 (s, 3H), 4.39 (q, J¼7.2 Hz, 2H), 5.14 (s,1H), 6.62 (d,
3H), 4.33 (q, J¼7.2 Hz, 2H), 6.9 (d, J¼9.0 Hz, 1H), 7.19e7.25 (m, 2H),
7.33 (t, J¼7.5 Hz, 2H), 7.47 (d, J¼8.1 Hz, 1H), 7.56 (s, 1H), 8.00 (s, 1H),
J¼8.7 Hz, 1H), 6.94e7.00 (m, 4H), 7.27 (d, J¼8.7 Hz, 1H), 7.56 (s, 1H).
13C NMR (100 MHz, CDCl3):
d
13.9, 21.3, 44.9, 62.2, 109.9, 117.7, 118.8
1
8.18 (d, J¼8.4 Hz, 1H). 13C NMR (100 MHz, CDCl3):
d
14.0, 62.1, 91.7
(q, JCeF¼273 Hz, CF3), 121.5, 124.9, 129.5, 131.7, 131.8, 137.1, 140.1,
(q, 2JCeF¼33 Hz, CF3), 117.2, 118.4, 121.1, 122.5 (q, 1JCeF¼285 Hz, CF3),
142.7 (q, 2JCeF¼38 Hz, CF3), 149.1, 164.3. 19F NMR (282 MHz, CDCl3):
123.0, 124.1, 126.7, 128.0, 128.8, 130.5, 134.6, 137.8, 143.0,
d
65.7 (s, 3F, CF3). MS (ESI): m/z¼495.0 (MþNa)þ. HRMS (ESI): m/z
155.7, 162.2. 19F NMR (282 MHz, CDCl3):
d
71.7 (s, 3F, CF3). MS
calcd for (C20H16BrF3O3SþNa)þ: 494.9898; found: 494.9848.
(ESI): m/z¼448.0 (MþNa)þ. HRMS (ESI): m/z calcd for
(C19H14F3NO5SþNa)þ: 448.0398; found: 448.0437.
4.2.14. 2-(Trifluoromethyl)-2-(p-tolylthio)-3-ethoxycarbonyl-6-
bromo-2H-chromene (4cb). Yield 36%, yellow solid, mp 96e98 ꢀC.
IR (KBr): 1732, 1625, 1557, 1476, 1368, 1341, 1276, 1235, 1217, 1198,
4.2.9. 2-(Trifluoromethyl)-3-ethoxycarbonyl-4-(p-tolylthio)-4H-
chromene (3ab). Yield 52%, white solid, mp 64e66 ꢀC. IR (KBr):
1724,1677,1592,1487, 1460, 1377,1299,1242, 1220, 1188, 1151,1090,
1166, 1024, 1007, 924, 886, 807 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
d
1.29 (t, J¼7.2 Hz, 3H), 2.26 (s, 3H), 4.23 (q, J¼7.2 Hz, 2H), 6.73 (d,
996, 813, 791, 761 cmꢁ1
.
1H NMR (300 MHz, CDCl3):
d
1.33 (t,
J¼9.0 Hz, 1H), 7.00 (d, J¼8.4 Hz, 2H), 7.19e7.21 (m, 1H), 7.29 (d,
J¼7.2 Hz, 3H), 2.22 (s, 3H), 4.32 (q, J¼7.2 Hz, 2H), 5.15 (s, 1H), 6.65
J¼8.1 Hz, 2H), 7.37 (d, J¼8.7 Hz, 1H), 7.41 (s, 1H). 13C NMR (100 MHz,
2
(d, J¼8.4 Hz, 1H), 6.86 (q, J¼7.1 Hz, 4H), 7.06e7.15 (m, 2H), 7.37 (d,
CDCl3):
d
14.0, 21.3, 61.7, 91.1 (q, JCeF¼32 Hz, CF3), 115.1, 118.6,
J¼7.5 Hz, 1H). 13C NMR (100 MHz, CDCl3):
d
13.8, 21.2, 45.5, 62.0,
120.6, 122.4, 122.8 (q, 1JCeF¼285 Hz, CF3), 123.8, 129.4, 130.9, 135.4,
109.9, 116.0, 119.0 (q, 1JCeF¼273 Hz, CF3), 119.4, 125.3, 125.6, 128.7,
135.5, 137.7, 140.6, 150.0, 162.2. 19F NMR (282 MHz, CDCl3):
d 71.0 (s,
129.3, 129.4,137.0,139.8,142.9 (q, 2JCeF¼38 Hz, CF3),150.2,164.7. 19
F
3F, CF3). MS (ESI): m/z¼495.0 (MþNa)þ. HRMS (ESI): m/z calcd for
NMR (282 MHz, CDCl3):
d
65.8 (s, 3F, CF3). MS (ESI): m/z¼417.0
(C20H16BrF3O3SþNa)þ: 494.9898; found: 494.9848.
(MþNa)þ. HRMS (ESI): m/z calcd for (C20H17F3O3SþNa)þ: 417.0798;
found: 417.0743.
4.2.15. 2-(Trifluoromethyl)-3-ethoxycarbonyl-4-(p-tolylthio)-6-
nitro-4H-chromene (3db). Yield 41%, yellow solid, mp 113e115 ꢀC. IR
(KBr): 1735,1676,1536,1483,1348,1302,1243,1205,1165,1087,1019,
4.2.10. 2-(Trifluoromethyl)-2-(p-tolylthio)-3-ethoxycarbonyl-2H-
chromene (4ab). Yield 35%, yellow oil. IR (KBr): 1731, 1609, 1539,
1488, 1456, 1369, 1291, 1236, 1218, 1197, 1170, 1120, 1007, 881, 811,
838, 819, 749 cmꢁ1.1H NMR (300 MHz, CDCl3):
d
1.40 (t, J¼7.2 Hz, 3H),
2.29 (s, 3H), 4.40 (q, J¼7.2 Hz, 2H), 5.20 (s, 1H), 6.83 (d, J¼9.3 Hz, 1H),
758 cmꢁ1. 1H NMR (300 MHz, CDCl3):
d
1.36 (t, J¼7.2 Hz, 3H), 2.32
6.94 (q, J¼8.1 Hz, 4H), 8.03 (d, J¼8.7 Hz, 1H), 8.36 (s, 1H). 13C NMR
(s, 3H), 4.30 (q, J¼7.2 Hz, 2H), 6.91 (d, J¼8.1 Hz, 1H), 7.04 (q,
(100 MHz, CDCl3): d 13.9, 21.2, 44.6, 62.5, 110.9, 117.0, 118. 6 (q,
J¼8.1 Hz, 3H), 7.16 (d, J¼7.5 Hz, 1H), 7.37 (q, J¼7.3 Hz, 3H), 7.60 (s,
1JCeF¼273 Hz, CF3), 121.0, 124.1, 124.4, 125.5, 129.7, 136.9, 140.6, 142.1
1H). 13C NMR (100 MHz, CDCl3):
d 14.1, 21.3, 61.5, 91.0 (q,
(q, 2JCeF¼39 Hz, CF3), 145.0, 153.8, 163.8. 19F NMR (282 MHz, CDCl3):
2JCeF¼32 Hz, CF3), 116.9, 118.9, 121.1, 123.0 (q, JCeF¼285 Hz, CF3),
d
66.6 (s, 3F, CF3). MS (ESI): m/z¼462.0 (MþNa)þ. HRMS (ESI): m/z
1
123.1, 124.2, 128.8, 129.4, 133.1, 137.1, 137.7, 140.3, 150.2, 164.7. 19F
calcd for (C20H16F3NO5SþNa)þ: 462.0598; found: 462.0593.
NMR (282 MHz, CDCl3):
d
70.0 (s, 3F, CF3). MS (ESI): m/z¼417.1
(MþNa)þ. HRMS (ESI): m/z calcd for (C20H17F3O3SþNa)þ: 417.0798;
4.2.16. 2-(Trifluoromethyl)-2-(p-tolylthio)-3-ethoxycarbonyl-6-
nitro-2H-chromene (4db). Yield 34%, yellow solid, mp 105e106 ꢀC.
IR (KBr): 1731, 1620, 1530, 1478, 1369, 1342, 1273, 1222, 1199, 1165,
found: 417.0743.
4.2.11. 2-(Trifluoromethyl)-3-ethoxycarbonyl-4-(p-tolylthio)-6-
chloro-4H-chromene (3bb). Yield 53%, yellow solid, mp 92e94 ꢀC.
IR (KBr): 1716, 1650, 1597, 1477, 1372, 1359, 1295, 1276, 1245, 1194,
1126, 1005, 928, 890, 816, 747 cmꢁ1 1H NMR (300 MHz, CDCl3):
.
d
1.38 (t, J¼7.2 Hz, 3H), 2.29 (s, 3H), 4.34 (q, J¼7.2 Hz, 2H), 6.98e7.05
(m, 3H), 7.34 (d, J¼8.4 Hz, 2H,), 7.55 (s, 1H), 8.01 (s, 1H), 8.20 (d,
1151, 1118, 1095, 994, 812, 786 cmꢁ1
.
1H NMR (300 MHz, CDCl3):
J¼9.0 Hz, 1H). 13C NMR (100 MHz, CDCl3):
d 14.0, 21.2, 62.0, 91.8 (q,
1
d
1.41 (t, J¼7.2 Hz, 3H), 2.30 (s, 3H), 4.40 (q, J¼7.2 Hz, 2H), 5.15 (s,
2JCeF¼33 Hz, CF3), 117.2, 118.5, 121.1, 122.5 (q, JCeF¼285 Hz, CF3),
1H), 6.67 (d, J¼8.7 Hz, 1H), 6.93e6.99 (m, 4H), 7.12 (d, J¼8.9 Hz, 1H),
123.1, 124.0, 128.0, 129.6, 134.5, 137.8, 141.1, 143.0, 155.7, 162.2. 19F
7.42 (s,1H). 13C NMR (100 MHz, CDCl3):
d
13.9, 21.2, 45.0, 62.1, 109.8,
NMR (282 MHz, CDCl3):
d
71.6 (s, 3F, CF3). MS (ESI): m/z¼462.0
1
117.4, 118.8 (q, JCeF¼273 Hz, CF3), 121.1, 124.9, 128.7, 128.8, 129.5,
(MþNa)þ. HRMS (ESI): m/z calcd for (C20H16F3NO5SþNa)þ:
130.4, 137.0, 140.1, 142.7 (q, 2JCeF¼38 Hz, CF3), 148.6, 164.3. 19F NMR
462.0598; found: 462.0593.
(282 MHz, CDCl3):
d
66.1 (s, 3F, CF3). MS (ESI): m/z¼451.0 (MþNa)þ.
HRMS (ESI): m/z calcd for (C20H16ClF3O3SþNa)þ: 451.0398; found:
4 . 2 .17 . 2 - ( Tr i fl u o r o m e t h y l ) - 3 - e t h o x y c a r b o n yl - 4 - ( 4 -
methoxyphenylthio)-6-chloro-4H-chromene (3bc). Yield 46%, white
solid, mp 78e79 ꢀC. IR (KBr): 1730, 1671, 1590, 1494, 1374, 1356,
1294, 1245, 1203, 1184, 1147, 1088, 1029, 999, 834, 815, 754 cmꢁ1. 1H
451.0353.
4.2.12. 2-(Trifluoromethyl)-2-(p-tolylthio)-3-ethoxycarbonyl-6-
chloro-2H-chromene (4bb). Yield 36%, yellow solid, mp 94e96 ꢀC.
IR (KBr): 1733, 1647, 1560, 1477, 1458, 1370, 1339, 1277, 1234, 1215,
NMR (300 MHz, CDCl3):
d
1.41 (t, J¼7.2 Hz, 3H), 3.76 (s, 3H), 4.40 (q,
J¼7.2 Hz, 2H), 5.11 (s, 1H), 6.65e6.71 (m, 3H), 6.95 (d, J¼9.0 Hz, 2H),
1198, 1171, 1009, 884, 812, 735 cmꢁ1
.
1H NMR (300 MHz, CDCl3):
7.09e7.13 (m, 1H), 7.43e7.44 (m, 1H). 13C NMR (100 MHz, CDCl3):
1
d
1.35 (t, J¼7.2 Hz, 3H), 2.32 (s, 3H), 4.40 (q, J¼7.2 Hz, 2H), 6.85 (d,
d
13.9, 45.1, 55.3, 62.2, 109.7, 114.3, 117.4, 118.8 (q, JCeF¼273 Hz,
2
J¼8.7 Hz, 1H), 7.06 (d, J¼7.8 Hz, 2H), 7.13 (s, 1H), 7.29 (d, J¼8.7 Hz,
CF3), 119.0, 121.1, 128.7, 128.8, 130.4, 138.7, 142.8 (q, JCeF¼38 Hz,

X. Li et al. / Tetrahedron 68 (2012) 8011e8017
8017
CF3), 148.6, 161.2, 164.4. 19F NMR (282 MHz, CDCl3):
d
66.5 (s, 3F,
1213, 1179, 1130, 1010, 878, 853, 822 cmꢁ1
CDCl3):
7.35 (s, 1H), 7.48 (d, J¼9.0 Hz,1H), 7.56 (s, 1H), 7.68 (d, J¼9.0 Hz, 2H),
.
1H NMR (300 MHz,
CF3). MS (ESI): m/z¼466.9 (MþNa)þ. HRMS (ESI): m/z calcd for
d
1.34 (t, J¼7.0 Hz, 3H), 4.31 (q, J¼7.0 Hz, 2H), 6.78 (d, 1H),
(C20H16ClF3O4SþNa)þ: 467.0302; found: 467.0298.
Crystal data for C20H16ClF3O4S: MW¼444.84; temperature:
8.11e8.18 (m, 2H). 13C NMR (100 MHz, CDCl3):
d 14.0, 62.0, 91.2 (q,
1
298(2) K; wavelength: 0.71 A; triclinic, space group: P-1;
2JCeF¼33 Hz, CF3), 118.0, 119.8, 121.9, 123.4 (q, JCeF¼285 Hz, CF3),
ꢀ
a¼7.5487(6) A, b¼14.1958(11) A, c¼20.5260(15) A;
a
¼98.06(10)ꢀ,
123.8, 127.9, 128.0, 129.4, 132.6, 135.5, 137.7, 140.6, 149.4, 162.6. 19F
ꢀ
ꢀ
ꢀ
3
ꢀ
ꢀ
b
¼100.30(10)ꢀ,
g
¼104.64(10) ; V¼2053.7(3) A ; Z¼4, Dc¼1.439 mg/
NMR (282 MHz, CDCl3):
d
70.7 (s, 3F, CF3). MS (ESI): m/z¼526.0
m3; absorption coefficient: 0.338 mmꢁ1; F(000)¼912; crystal size:
(MþNa)þ. HRMS (ESI): m/z calcd for (C19H13BrF3NO5SþNa)þ:
0.26ꢂ0.22ꢂ0.16 mm; 1.51<
q
<25.50; reflections collected: 10,910,
525.9498; found: 525.9542.
R(int)¼0.0168; absorption correction: semi-empirical; final R in-
dices: R1¼0.0497, wR2¼0.1182. CCDC number is 870783.
Acknowledgements
4.2.18. 2-(Trifluoromethyl)-2-(4-methoxyphenylthio)-3-ethox-
ycarbonyl-6-chloro-2H-chromene (4bc). Yield 30%, yellowish solid,
mp 66e68 ꢀC. IR (KBr): 1731, 1592, 1570, 1494, 1479, 1368, 1277,
Financial support for this project was provided by The National
Natural Science Foundation of China (NNSFC, Nos. 20972178,
21032006 and 21102163) and National Basic Research Program
(No. 2007CB80800). We also thank Dr. Huiling Jiang for this paper’s
modification.
1253, 1214, 1162, 1128, 1028, 1005, 884, 824, 737 cmꢁ1 1H NMR
.
(300 MHz, CDCl3):
d
1.36 (t, J¼7.0 Hz, 3H), 3.79 (s, 3H), 4.30
(q¼7.0 Hz, 2H), 6.78 (d, J¼9.0 Hz, 2H), 6.86 (d, J¼8.4 Hz, 1H), 7.13 (s,
1H), 7.27e7.31 (m, 1H), 7.39 (d, J¼8.7 Hz, 2H), 7.48 (s, 1H). 13C NMR
Supplementary data
(100 MHz, CDCl3):
d
14.0, 55.3, 61.7, 91.1 (q, 2JCeF¼33 Hz, CF3), 114.2,
118.0, 118.1, 120.1, 122.5, 122.8 (q, 1JCeF¼285 Hz, CF3), 127.9, 132.5,
Supplementary data associated with this article can be found in
the online version, at http://dx.doi.org/10.1016/j.tet.2012.06.101.
These data include MOL files and InChiKeys of the most important
compounds described in this article.
135.4, 139.3, 149.5, 161.3, 162.7. 19F NMR (282 MHz, CDCl3):
d 70.9 (s,
3F, CF3). MS (ESI): m/z¼466.8 (MþNa)þ. HRMS (ESI): m/z calcd for
(C20H16ClF3O4SþNa)þ: 467.0302; found: 467.0298.
4.2.19. 2-(Trifluoromethyl)-3-ethoxycarbonyl-4-(4-nitrophenylthio)-
6-chloro-4H-chromene (3bd). Yield 35%, yellow solid, mp
110e111 ꢀC. IR (KBr): 1732, 1679, 1596, 1521, 1482, 1343, 1280, 1225,
1192, 1117, 1081, 995, 853, 814, 741 cmꢁ1. 1H NMR (300 MHz, CDCl3):
References and notes
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d
1.41 (t, J¼7.0 Hz, 3H), 4.41 (q, J¼7.0 Hz, 2H), 5.37 (s, 1H), 6.75 (d,
J¼8.7 Hz, 1H), 7.20 (d, J¼8.7 Hz, 1H), 7.27e7.30 (m, 2H), 7.48 (s, 1H),
8.04 (d, J¼8.1 Hz, 2H). 13C NMR (100 MHz, CDCl3):
d 13.9, 21.2, 45.0,
62.1,109.8,117.4,118.8 (q,1JCeF¼273 Hz, CF3),121.1,124.9,128.7,128.8,
129.5, 130.4, 137.0, 140.1, 142.7 (q, 2JCeF¼38 Hz, CF3), 148.6, 164.3. 19
F
NMR (282 MHz, CDCl3):
d
65.6 (s, 3F, CF3). MS (ESI): m/z¼482.0
4. (a) Raj, T.; Bhatia, R. K.; Kapur, A.; Sharma, M.; Saxena, A. K.; Ishar, M. P. S. Eur. J.
Med. Chem. 2010, 45, 790e794; (b) Sabry, N. M.; Mohamedc, H. M.; Shawky, E.;
Khattab, A. E. H.; Motlaq, S. S.; El-Agrody, A. M. Eur. J. Med. Chem. 2011, 46,
765e772.
(MþNa)þ. HRMS (ESI): m/z calcd for (C19H13ClF3NO5SþNa)þ:
482.0098; found: 482.0047.
5. (a) Kuarm, B. S.; Reddy, Y. T.; Madhav, J. V.; Crooks, P. A.; Rajitha, B. Bioorg. Med.
Chem. Lett. 2011, 21, 524e527; (b) Rai, U. S.; Isloor, A. M.; Shetty, P.; Vijesh, A. M.;
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2695e2699; (c) Kamdar, N. R.; Haveliwala, D. D.; Mistry, P. T.; Patel, S. K. Med.
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4.2.20. 2-(Trifluoromethyl)-2-(4-nitrophenylthio)-3-ethoxycarbonyl-
6-chloro-2H-chromene (4bd). Yield 10%, yellow solid, mp
113e115 ꢀC. IR (KBr): 1725, 1597, 1519, 1476, 1344, 1277, 1234, 1214,
1180, 1128, 1009, 880, 853, 748, 686 cmꢁ1 1H NMR (300 MHz,
.
6. Lago, J. H. G.; Ramos, C. S.; Casanova, D. C. C.; Morandim, A. A.; Bergamo, D. C.
CDCl3):
d
1.34 (t, J¼7.2 Hz, 3H), 4.30 (q, J¼7.2 Hz, 2H), 6.84 (d,
~
B.; Cavalheiro, A. J.; Bolzani, V. S.; Furlan, M.; Guilharaes, E. F.; Young, M. C. M.;
Kato, M. J. J. Nat. Prod. 2004, 67, 1783e1788.
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J¼8.4 Hz, 1H), 7.21 (s, 1H), 7.33 (d, J¼8.4 Hz, 1H), 7.57 (s, 1H), 7.68 (d,
J¼9.0 Hz, 2H), 8.13 (d, J¼9.0 Hz, 2H). 13C NMR (100 MHz, CDCl3):
d
14.0, 21.3, 61.7, 91.2 (q, 2JCeF¼33 Hz, CF3), 118.2, 120.1, 122.4, 122.8
8. (a) Yavari, I. H.; Djahaniani, H.; Nasiri, F. Tetrahedron 2003, 59, 9409e9412; (b)
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(q, 1JCeF¼285 Hz, CF3), 123.8, 127.9, 128.0, 129.4, 132.6, 135.5, 137.7,
140.6, 149.4, 162.6. 19F NMR (282 MHz, CDCl3):
d 71.6 (s, 3F, CF3). MS
(ESI): m/z¼482.0 (MþNa)þ. HRMS (ESI): m/z calcd for
ꢁ
ꢁ~
Adv. 2011, 1, 1050e1059; (f) Aleman, J.; Alvarado, C.; Marcos, V.; Nunez, A.;
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13. Kharrat, S. K.; Laurent, P.; Blancou, H. J. Org. Chem. 2006, 71, 8637e8640.
14. Wu, Y. C.; Li, H. J.; Liu, L.; Demoulin, N.; Liu, Z.; Wang, D.; Chen, Y. J. Adv. Synth.
Catal. 2011, 353, 907e912.
15. (a) Evdokimov, N. M.; Kireev, A. S.; Yakovenko, A. A.; Antipin, M. Y.; Magedova,
I. V.; Kornienko, A. Tetrahedron Lett. 2006, 47, 9309e9312; (b) Evdokimov, N. M.;
Kireev, A. S.; Yakovenko, A. A.; Antipin, M. Y.; Magedova, I. V.; Kornienko, A. J.
Org. Chem. 2007, 72, 3443e3453.
4.2.21. 2-(Trifluoromethyl)-3-ethoxycarbonyl-4-(4-nitrophenylthio)-
6-bromo-4H-chromene (3cd). Yield 36%, yellow solid, mp
98e100 ꢀC. IR (KBr): 1731, 1676, 1597, 1515, 1148, 1345, 1284, 1227,
1200,1141,1084,1021, 853, 814, 742 cmꢁ1.1H NMR (300 MHz, CDCl3):
d
1.41 (t, J¼7.0 Hz, 3H), 4.41 (q, J¼7.0 Hz, 2H), 5.36 (s, 1H), 6.69 (d,
J¼8.4 Hz, 1H), 7.27e7.35 (m, 3H), 7.63 (s, 1H), 8.04 (d, J¼8.4 Hz, 2H).
13C NMR (100 MHz, CDCl3):
d 13.9, 45.6, 62.5, 109.5, 117.8, 118.6 (q,
1JCeF¼273 Hz, CF3), 120.1, 123.4, 128.7, 129.7, 131.1, 137.3, 137.4, 143.1
(q, 2JCeF¼39 Hz, CF3), 148.4, 148.7, 164.0. 19F NMR (282 MHz, CDCl3):
d
65.8 (s, 3F, CF3). MS (ESI): m/z¼526.0 (MþNa)þ. HRMS (ESI): m/z
calcd for (C19H13BrF3NO5SþNa)þ: 525.9498; found: 525.9542.
4.2.22. 2-(Trifluoromethyl)-2-(4-nitrophenylthio)-3-ethoxycarbonyl-
6-bromo-2H-chromene (4cd). Yield 11%, yellow solid, mp
111e113 ꢀC. IR (KBr): 1725, 1597, 1517, 1475, 1371, 1343, 1278, 1234,
16. Pang, W.; Han, J. W.; Zhao, J. W.; Zhu, S. Z. Synthesis 2011, 20, 3364e3370.