One-pot sequential combination of multi-component and multi-catalyst: Synthesis of 5-aminobenzofurans from aminophenol and ketene acetals

Article abstract of DOI:10.1016/j.tet.2012.09.090

The reaction between p-aminophenols 1 and various ketene acetals 2 in the presence of hypervalent iodine is described. The results show that 2- and 3-substituted 5-sulfonamidobenzofurans 3 are obtained in moderate to good yields from p-aminophenols and ke

Full text of DOI:10.1016/j.tet.2012.09.090

Tetrahedron 68 (2012) 10201e10208
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Tetrahedron
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One-pot sequential combination of multi-component and multi-catalyst:
synthesis of 5-aminobenzofurans from aminophenol and ketene acetals
,
a
b
Cheng-Wen Yang a, Yue-Xia Bai a, Ni-Tao Zhang a, Cheng-Chu Zeng a , Li-Ming Hu , Hong-Yu Tian
*
a College of Life Science & Bioengineering, Beijing University of Technology, Beijing 100124, China
b School of Food Chemistry, Beijing Technology and Business University, Beijing 100048, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 June 2012
Received in revised form 18 September 2012
Accepted 21 September 2012
Available online 26 September 2012
The reaction between p-aminophenols 1 and various ketene acetals 2 in the presence of hypervalent
iodine is described. The results show that 2- and 3-substituted 5-sulfonamidobenzofurans 3 are obtained
in moderate to good yields from p-aminophenols and ketene acetals.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Multi-catalyst
Oxidation
Cyclization
5-Aminobenzofurans
Alkene acetals
1. Introduction
oxidation followed by an intermolecular Michael reaction, a second
anodic oxidation and an intramolecular Michael reaction.10
Natural and synthetic benzofurans are of great interest due to
their various biological activities.1 Moreover, they are used as
electroluminescent materials, liquid crystals, and organic dyes in
material chemistry.2 As a consequence, newer and more efficient
procedures are desirable for the syntheses of these compounds.
Structurally, benzofurans can be constructed either through
[4þ2] cycloaddition of furan derivatives and dienophiles3 or starting
from benzene derivatives.4 The Michael addition and subsequent
cyclization of benzoquinone with active methylene derivatives may
provide an alternative approach for the synthesis of benzofurans.5
Engler and co-workers elegantly explored the Lewis acid-
promoted reaction of 2-alkoxy-1,4-benzoquinones,6 quinone-1,4-
diimine,7 and quinone monoimine derivatives8 with styrenyl sys-
tems yielding primarily either 2-aryl-2,3-dihydrobenzofuran or
-dihydroindole products. Recently, Liu and co-workers reported that
the Michael addition and cyclization of ketene dithioacetals and 1,4-
benzoquinones activated by CuBr2 and BF3$OEt2 gave 5-
hydroxybenzofurans.9 On the other hand, others and we have
demonstrated that the electrochemical oxidation of catechols in the
presence of polarized alkenes can generate polyhydroxylated ben-
zofurans or indoles in a sequence of reactions beginning with anodic
Based on the above understanding, we hypothesize that the in
situ oxidation of 4-aminophenol derivatives using hypervalent
iodine11 ought to generate quinone monoimine 1eO. When this type
of reactive intermediate is treated with a polarized alkene in the
presence of dual catalysis, 5-aminobenzofurans may be produced
(Fig. 1). In the present work, we describe the efficient synthesis of
highly functionalized 5-aminobenzofurans from simple starting
material under mild conditions in a two-step, one-pot process.
2. Results and discussion
2.1. Synthesis of starting ketene S,S-acetals and N,S-acetals
a
-Benzoyl ketene S,S-acetals 2aed (see Table 2) were prepared
from acetophenone and methanedithione12
;
a
-acetyl-, -amino-
a
carbonyl-, a-nitro-, and a-cyano-ketene S,S-acetals (2eeh; Table 2)
were prepared according to known procedures.13
For the synthesis of N,S-acetals (2ieq), we note that a literature
indicated that a mixture of S,N- and N,N-ketals, which were difficult
to separate, was always afforded. Therefore, n-BuLi was used to
generate exclusively the mono-substituted N,S-acetals.14 However,
after extensive optimization of the experimental conditions,
we were delightedly to find that the desired N,S-acetal could
be selectively obtained by refluxing equivalent amounts of the
* Corresponding author. Fax: þ86 10 67392001; e-mail address: zengcc@bjut.e-
du.cn (C.-C. Zeng).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2012.09.090

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C.-W. Yang et al. / Tetrahedron 68 (2012) 10201e10208
Fig. 1. A two-step, one-pot approach for the synthesis of 5-aminobenzofurans 3.
S,S-acetals and the desired amines in toluene for 16 h (45e70%
yields; note Scheme 1).
Since the starting material, 1a, was not fully consumed, we
reasoned that these low yields might have arisen because an in-
sufficient amount of oxidant was used. In accord with this idea, the
use of 1.5 equiv of PhI(OAc)2 showed that the starting material was
consumed in 1.5 h and the yield of 3a increased to 48% (Table 1,
entry 3); the use of 2 equiv of oxidant resulted in a decrease to 36%
in yield (Table 1, entry 4).
Since the formation of the benzofuran framework is believed to
occur via a two-step, one-pot sequence, we reasoned that the order
of addition of the reagents should play an important role in the
success of the process. To test this idea,1a and the oxidant, PhI(OAc)2,
were first mixed at room temperature, followed by the addition of 2a
and co-catalysts under the conditions reported above9 10 min later.
This change significantly improved the reaction outcomes and 61% of
3a was isolated (entry 5). On the basis of these results, the optimized
condition was found to use a 1.0:1.5:1.0 ratio of 1a to PhI(OAc)2 to 2a,
with 2.0 mol % of CuBr2 and 10 mol % of BF3$Et2O as catalysts (in
4.0 mL MeCN)9 and at room temperature; the preferred order of
addition proved to be aminophenol 1a and PhI(OAc)2, followed by
the addition of ketene acetals 2, BF3$Et2O and CuBr2 10 min later.
Then, the scope of this two-step, one-pot benzofuran synthesis
wasinvestigated under theoptimized conditions. AsshowninTable 2,
Scheme 1. The synthesis of N,S-acetals 2ieq.
2.2. Synthesis of benzofurans
Our evaluation of the possibility of achieving a one-pot, two-
step synthesis of benzofurans from aminophenol derivatives and
acetals commenced by using the sulfonamide-protected amino-
phenol 1a and para-methylbenzoyl S,S-acetal 2a as model com-
pounds (Scheme 2). In a first experiment, the reaction of 1a with 2a
was allowed to proceed at room temperature in the presence of
1 equiv of PhI(OCOCF3)2 as oxidant and the dual catalysts (BF3$Et2O
and CuBr2). This led to the desired benzofuran 3a in only 11% yield
(Table 1, entry 1). The use of longer reaction times (from 12 to 48 h)
did not lead to an increase in yield. However, under the same
conditions, the yield of 3a increased to 24% when PhI(OAc)2 was
used as the oxidant (Table 1, entry 2).
the
a-methoxybenzoyl ketene S,S-acetal 2b afforded adduct 3b in 65%
yield (entry 2). Similarly, 3c and 3d were generated in 52% and 49%
yields, respectively, from
a-benzoyl ketene S,S-acetal 2c and 2d,
CH3
O
OH
O
TsHN
H3C
SCH3
SCH3
1. hypervalent iodine
+
SCH3
O
.
2. CuBr2, BF3 Et2O
NHTs
1a
CH3CN
2a
3a
Scheme 2. The synthesis of 3a from sulfonamide-protected aminophenol 1a and p-methylbenzoyl S,S-acetal 2a.
although in a bit lower yields (entries 3 and 4). To investigate the
influence of the electron-withdrawing group (EWG) on the reaction
yield, acetyl-, aminocarbonyl-, nitro-, and cyano-substituted ketene
S,S-acetals 2ee h were also synthesized and allowed to react with 1a
under the same conditions; it was observed that the stronger of the
electron-withdrawing properties of the EWG, the higher of the yields.
For example, when the EWG are acetyl- or aminocarbonyl-, 2e and 2f
gave 42% and 35% of corresponding benzofurans 3e and 3f (entries
5e6). However, the yields of the corresponding benzofurans 3g and
3h increased to 61% and 63% yields, respectively, when the EWG is
replaced by nitro or cyano groups, (entries 7e8).
Table 1
Optimization of conditions for the synthesis of 3a from sulfonamide-protected
aminophenol 1a and p-methylbenzoyl S,S-acetal 2a
Entry
Oxidant
Ratio of
oxidant
Addition
sequence
Time (h)
Yield (%)
1
2
3
4
5
PhI(OCOCF3)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
PhI(OAc)2
1.0 equiv
1.0 equiv
1.5 equiv
2.0 equiv
1.5 equiv
Method a
Method a
Method a
Method a
Method b
12
12
1.5
1.5
1.5
11
24
48
36
61
Method a: 1a, 2a and oxidant were firstly added followed by the addition of catalysts
BF3$Et2O and CuBr2 10 min later.
Method b: 1a and oxidant were firstly added followed by the addition of 2a,
BF3$Et2O, and CuBr2 10 min later.
Subsequently, the ketene N,S-acetals were subjected to reaction
with 1a in the presence of PhI(OAc)2 as oxidant. As shown in Table 2

C.-W. Yang et al. / Tetrahedron 68 (2012) 10201e10208
10203
Table 2
Yields of benzofurans 3
Entry
1
Ketene acetal
Product
Yield (%)
O
O
SCH3
CH3
OH
1a
TsHN
TsHN
1
61
65
SCH3
SCH3
3a
2a
H3C
O
O
O
SCH3
SCH3
OCH3
TsHN
OH
1a
TsHN
2
3
SCH3
3b
2b
H3CO
O
O
O
SCH3
SCH3
OH
TsHN
TsHN
52
SCH3
1a
2c
O
O
3c
O
SCH3
SCH3
Cl
OH
1a
TsHN
TsHN
4
5
6
49
42
35
SCH3
3d
2d
O
Cl
O
O
SCH3
SCH3
OH
1a
TsHN
TsHN
SCH3
2e
O
3e
O
O
SCH3
SCH3
NH2
TsHN
1a
H2N
SCH3
3f
2f
O
NO2
SCH3
SCH3
TsHN
O2N
7
8
9
1a
1a
1a
61
63
55
SCH3
3g
O
2g
CN
SCH3
SCH3
TsHN
NC
SCH3
3h
O
2h
O
O
NHPr
SCH3
CH3
TsHN
NHPr
3i
2i
O
H3C
O
O
NHPr
SCH3
OCH3
TsHN
10
1a
72
NHPr
3j
2j
H3CO
O
O
O
NHPr
SCH3
TsHN
11
12
1a
1a
54
49
NHPr
2k
O
3k
O
O
NHPr
SCH3
Cl
TsHN
NHPr
2l
Cl
O
3l
O
O
NHPr
SCH3
TsHN
13
1a
58
NHPr
3m
2m
O
(continued on next page)

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C.-W. Yang et al. / Tetrahedron 68 (2012) 10201e10208
Table 2 (continued )
Entry
1
Ketene acetal
Product
Yield (%)
47
NO2
NHPr
TsHN
O2N
14
15
1a
1a
SCH3
NHPr
2n
O
3n
O
O
NHBn
SCH3
CH3
TsHN
73
NHBn
3o
2o
H3C
O
O
O
NHBn
SCH3
OCH3
TsHN
16
17
1a
1a
76
64
NHBn
3p
2p
H3CO
O
O
O
NHBn
SCH3
Cl
TsHN
NHBn
3q
2q
Cl
O
O
O
SCH3
SCH3
CH3
TsHN
H3C
18
19
69
64
SCH3
3r
2a
H3C
O
O
O
NHPr
SCH3
CH3
TsHN
H3C
1b
NHPr
3s
2i
H3C
O
and Scheme 3, the reaction of ketene N,S-acetals 2ien, wherein
one eSCH3 group was substituted by NHPr, and 1a under the same
conditions afforded moderate to good yields of corresponding ben-
zofurans 3ien. In addition, benzylamino-substituted ketene N,S-ac-
etals 2oeq also generated benzofurans 3oeq in good yield (64e76%).
monoimine through binding to the imide and forms the dihy-
drofuran; whereas a dihydroindole is the main product using
excess amounts of Ti(IV) as the promoter due to its binding to the
C-1 carbonyl group of 4-(N-benzenesulfonyl)monoimine. Together
with the structural identification of the products in the present
Scheme 3. Synthesis of benzofurans 3aes.
Finally, methyl-substituted aminophenol 1b was investigated.
As shown in Table 2, benzofurans 3r and 3s were obtained in 69%
and 64% yield, respectively.
work, we can propose an oxidation and [3þ2] cycloaddition
sequence for the construction of benzofurans 3. As illustrated in
Scheme 4, the oxidation of N-(4-hydroxyphenyl)-benzenesulfona-
mide 1a and 1b gives quinone monoimine 5, which is coordinated
by BF3 to the benzenesulfonyl nitrogen atom to produce
intermediate 6. On the other hand, the ketene acetals 2 are
activated by CuBr2 to form 2-CuBr2 adduct. The Michael addition of
CuBr2-activated ketene acetals 2 to 6 at its ortho-position of the
carbonyl group, followed by aromatization, generates intermediate
8. Finally, the intramolecular nucleophilic vinylic substitution (SNV)
reaction produce benzofurans 3.9,15
2.3. Reaction mechanism
For the Lewis acid promoted reaction of 4-(N-benzenesulfonyl)
quinone monoimine derivatives and styrenes, the nature of the
Lewis acid promoter determines the regioselectivity, leading to the
formation of dihydrofuran or dihydroindoles.6b,8a When BF3$OEt2 is
used as the Lewis acid, it activates the 4-(N-benzenesulfonyl)

C.-W. Yang et al. / Tetrahedron 68 (2012) 10201e10208
10205
Scheme 4. A proposed reaction mechanism for the formation of benzofurans from p-tosylaminophenol and ketene acetals.
3. Conclusion
4.2. General procedure for the synthesis of ketene N,S-acetals
2ieq
In summary, we have developed a one-pot, two-step sequence
involving the combination of a multi-component and multi-
catalysis strategy for the synthesis of 5-aminobenzofurans from
aminophenols and ketene acetals. The reaction is initiated from the
oxidation of aminophenol by hypervalent iodine to form a quinone
monoimine. The intermediate is activated in situ by BF3 at the
benzenesulfonyl nitrogen atom to induce a regioselective Michael
addition with ketene acetals activated by CuBr2. Following
intramolecular SNV reaction, 5-aminobenzofurans are formed
in moderate to good yields. This method provides an environ-
mentally benign access to 5-aminobenzofurans with several active
functional groups for further derivatization under mild reaction
conditions.
To a 100 mL round bottomed flask equipped with a magnetic
stirrer and a condenser were added ketene S,S-acetals (20 mmol)
and amine (20 mmol) dissolved in 30 mL of toluene. The reaction
mixture was heated to reflux for about 16 h and then cooled to
room temperature. After removal of the solvents under reduced
pressure, 50 mL of water was added to the flask and the mixture
was extracted using ethyl acetate (3ꢁ200 mL). The combined or-
ganic layers were washed with brine (2ꢁ50 mL) and dried over
anhydrous MgSO4. The desired ketene N,S-acetals were obtained
after column chromatography eluted by petroleum ether and ethyl
acetate.
4.2.1. (E)-3-Methylthio-3-propylamino-1-p-tolylprop-2-en-1-one
4. Experimental
4.1. General
(2i).17 Yellowish powder, mp: 35e37 ꢂC; yield: 65%. 1H NMR
(400 MHz, CDCl3):
d
1.05 (t, 3H, J¼7.2 Hz, CH3), 1.75e1.77 (m, 2H,
CH2), 2.40 (s, 3H, CH3), 2.49 (s, 3H, SCH3), 3.38 (m, 2H, CH2), 5.62 (s,
1H, C]CH), 7.23 (d, 2H, J¼8.0 Hz, AreH), 7.78 (d, 2H, J¼8.0 Hz,
AreH), 11.94 (br, 1H, NH).
All melting points (mp) were measured with an XT4A Electro-
thermal apparatus equipped with a microscope and are un-
corrected. Infrared spectra (IR) were recorded as thin films on KBr
plates on a Bruker IR spectrophotometer and are expressed in v
(cmꢀ1). 1H and 13C NMR spectra were recorded on an AV 400 M
Bruker spectrometer (400 MHz for1H frequency, 100 MHz for 13C
frequency) in solvent (CDCl3 or DMSO-d6) with TMS as an internal
reference. MS data (ESI) were recorded on a Bruker esquire 6000
mass spectrometer. HR-MS (TOF-EI) were recorded on a GCT CA 127
Micronass UK mass spectrometer. All solvents were of commercial
quality and were dried and purified by standard procedures. N-(4-
hydroxyphenyl)benzenesulfonamides (1a and 1b) were synthe-
sized following reference procedures.16
4.2.2. (E)-1-(4-Methoxyphenyl)-3-methylthio-3-propylaminoprop-
2-en-1-one (2j).17 Yellowish powder, mp: 43e44 ꢂC; yield: 69%. 1H
NMR (400 MHz, CDCl3):
d
1.04 (t, 3H, J¼7.2 Hz, CH3), 1.68e1.77 (m,
2H, CH2), 2.48 (s, 3H, SCH3), 3.33e3.38 (m, 2H, CH2), 3.85 (s, 3H,
OCH3), 5.62 (s, 1H, C]CH), 6.92 (d, 2H, J¼8.8 Hz, AreH), 7.85 (d, 2H,
J¼8.8 Hz, AreH), 11.81 (br, 1H, NH).
4.2.3. (E)-3-Methylthio-1-phenyl-3-propylaminoprop-2-en-1-one
(2k).17 Yellowish liquid, yield: 60%. 1H NMR (400 MHz, CDCl3):
d
1.05 (t, 3H, J¼7.2 Hz, CH3), 1.71e1.77 (m, 2H, CH2), 2.49
(s, 3H, SCH3), 3.35e3.40 (m, 2H, CH2), 5.66 (s, 1H, C]CH),

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C.-W. Yang et al. / Tetrahedron 68 (2012) 10201e10208
7.39e7.45 (m, 3H, AreH), 7.87 (d, 2H, J¼8.8 Hz, AreH), 11.91 (br,
127.2, 128.9, 129.7, 130.0, 134.7, 136.4, 136.9, 143.3, 143.6, 152.1,
1H, NH).
163.7, 189.4; IR (KBr): n
3434, 2923, 1608 cmꢀ1; ESI-MS: m/z 449.8
[Mꢀ1]ꢀ, 473.9 [MþNa]þ; HREI-MS (m/z) calcd for C24H21NO4S2 (M)
4.2.4. (E)-1-(4-Chlorophenyl)-3-methylthio-3-propylaminoprop-2-
451.0912, found 451.0920.
en-1-one (2l).17 Yellowish powder, mp: 68e70 ꢂC; yield: 60%. 1H
NMR (400 MHz, CDCl3):
d
1.04 (t, 3H, J¼7.2 Hz, CH3), 1.69e1.76 (m,
4.3.2. N-[3-(4-Methoxybenzoyl)-2-(methylthio)benzofuran-5-yl]-4-
2H, CH2), 2.49 (s, 3H, SCH3), 3.34e3.39 (m, 2H, NHCH2), 5.60 (s, 1H,
C]CH), 7.37 (d, 2H, J¼8.8 Hz, AreH), 7.79 (d, 2H, J¼8.8 Hz, AreH),
11.91 (br, 1H, NH).
methylbenzene-sulfonamide (3b). Yellowish powder, yield: 65%;
mp: 130e131 ꢂC; 1H NMR (400 MHz, DMSO-d6):
d 2.32 (s, 3H, CH3),
2.62 (s, 3H, SCH3), 3.88 (s, 3H, OCH3), 7.03e7.06 (m, 4H, AreH), 7.31
(d, 2H, J¼7.6 Hz, AreH), 7.50e7.54 (m, 3H, AreH), 7.66 (d, 2H,
J¼7.6 Hz, AreH), 10.12 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6):
4.2.5. (E)-4-Methylthio-4-propylaminobut-3-en-2-one
(2m). Yellowish liquid, yield: 41%. 1H NMR (400 MHz, CDCl3):
d 14.2, 21.4, 56.0, 111.8, 112.8, 114.4, 117.0, 118.2, 127.1, 127.4, 130.0,
d
0.98 (t, 3H, J¼7.6 Hz, CH3), 1.61e1.70 (m, 2H, CH2), 2.05 (s, 3H,
CH3), 2.35 (s, 3H, SCH3), 3.26 (m, 2H, NHCH2), 4.95 (s, 1H, C]CH),
11.35 (br, 1H, NH); 13C NMR (100 MHz, DMSO-d6):
18.9, 28.7, 42.8,
2923, 2879, 1610,
131.3, 131.4, 134.7, 136.9, 143.6, 152.1, 162.6, 163.3, 188.3; IR (KBr): n
3435, 3172, 2934, 1599 cmꢀ1; ESI-MS: m/z 465.8 [Mꢀ1]ꢀ, 467.8
[Mþ1]þ, 489.8 [MþNa]þ; HREI-MS (m/z) calcd for C24H21NO5S2 (M)
467.0861, found 467.0869.
d
59.0, 71.5, 95.4, 163.0, 194.8; IR (KBr):
n
1571 cmꢀ1; ESI-MS: m/z 172.0 [Mꢀ1]ꢀ.
4.3.3. N-[3-Benzoyl-2-(methylthio)benzofuran-5-yl]-4-methylbenze-
4.2.6. (E)-N-[1-(Methylthio)-2-nitrovinyl]propan-1-amine
nesulfonamide (3c). Yellowish powder, yield: 52%; mp: 156e157 ꢂC;
(2n).18 Yellow powder, mp: 64e65 ꢂC; yield: 68%. 1H NMR
1H NMR (400 MHz, DMSO-d6):
d 2.32 (s, 3H, CH3), 2.63 (s, 3H, SCH3),
(400 MHz, CDCl3):
CH2), 2.45 (s, 3H, SCH3), 3.38e3.42 (m, 2H, NHCH2), 6.59 (s, 1H, C]
CH), 10.58 (br, 1H, NH).
d
1.02 (t, 3H, J¼7.2 Hz, CH3), 1.71e1.77 (m, 2H,
6.98e7.02 (m, 2H, AreH), 7.31 (d, 2H, J¼7.6 Hz, AreH), 7.48e7.56
(m, 5H, AreH), 7.64 (d, 2H, J¼7.6 Hz, AreH), 7.68e7.71 (m, 1H,
AreH), 10.14 (br, 1H, NH); 13C NMR (100 MHz, DMSO-d6):
d 14.0,
21.4, 111.8, 112.6, 116.4, 118.1, 127.0, 127.1, 128.5, 129.2, 130.0, 132.9,
4.2.7. (E)-3-Benzylamino-3-methylthio-1-p-tolylprop-2-en-1-one
134.8, 136.9, 139.2, 143.6, 152.1, 164.5, 189.8; IR (KBr): n 3436, 3242,
(2o).19 Yellowish powder, mp: 83e84 ꢂC; yield: 63%. 1H NMR
2920, 1600 cmꢀ1; ESI-MS: m/z 435.8 [Mꢀ1]ꢀ, 437.8 [Mþ1]þ, 459.7
[MþNa]þ; HREI-MS (m/z) calcd for C23H19NO4S2 (M) 437.0756,
found 437.0762.
(400 MHz, CDCl3):
d
2.50 (s, 3H, SCH3), 4.63 (d, 2H, J¼5.6 Hz, CH2),
5.70 (s, 1H, C]CH), 7.28e7.33 (m, 1H, AreH), 7.34e7.40 (m, 6H,
AreH), 7.81 (d, 2H, J¼8.4 Hz, AreH), 12.21 (br, 1H, NH).
4.3.4. N-[3-(4-Chlorobenzoyl)-2-(methylthio)benzofuran-5-yl]-4-
4.2.8. (E)-3-Benzylamino-1-(4-methoxyphenyl)-3-methylthioprop-
methylbenzene-sulfonamide (3d). Yellowish powder, yield: 49%;
2-en-1-one (2p).19 Pink powder, mp: 43e44 ꢂC; yield: 71%. 1H NMR
mp: 169e171 ꢂC; 1H NMR (400 MHz, DMSO-d6):
d 2.33 (s, 3H, CH3),
(400 MHz, CDCl3):
d
2.49 (s, 3H, SCH3), 3.87 (s, 3H, OCH3), 4.63 (d, 2H,
2.64 (s, 3H, SCH3), 6.99 (d, 1H, J¼2.0 Hz, AreH), 7.03 (dd, 1H,
J¼8.8 Hz, J¼2.0 Hz, AreH), 7.33 (d, J¼8.0 Hz, 2H, AreH), 7.51 (d, 2H,
J¼8.4 Hz, AreH), 7.54 (d, 1H, J¼8.8 Hz, AreH), 7.59 (d, 2H, J¼8.8 Hz,
AreH), 7.66 (d, 2H, J¼8.8 Hz, AreH), 10.15 (br, 1H, NH); 13C NMR
J¼5.6 Hz, CH2), 5.70 (s, 1H, C]CH), 6.93 (d, 2H, J¼8.8 Hz, AreH),
7.29e7.34 (m, 5H, AreH), 7.78 (d, 2H, J¼8.4 Hz, AreH),12.15 (br,1H, NH).
4.2.9. (E)-3-Benzylamino-1-(4-chlorophenyl)-3-methylthioprop-2-
(100 MHz, DMSO-d6): d 14.0, 21.4, 111.8, 112.4, 116.1, 118.1, 126.9,
en-1-one (2q).19 Yellowish powder, mp: 92e93 ꢂC; yield: 59%. 1H
127.1, 129.3, 130.1, 130.4, 134.9, 136.9, 137.6, 137.9, 143.6, 152.1, 164.9,
NMR (400 MHz, CDCl3):
CH2), 5.70 (s, 1H, C]CH), 6.93 (d, 2H, J¼8.8 Hz, AreH), 7.29e7.34
(m, 5H, AreH), 7.78 (d, 2H, J¼8.4 Hz, AreH), 12.15 (br, 1H, NH).
d
2.49 (s, 3H, SCH3), 4.63 (d, 2H, J¼5.6 Hz,
188.6; IR (KBr): n
3436, 3227, 2941, 1612, 1592 cmꢀ1; ESI-MS: m/z
469.8 [Mꢀ1]ꢀ, 471.7 [Mþ1]þ, 493.7 [MþNa]þ; HREI-MS (m/z) calcd
for C23H18NO4S2Cl (M) 451.0366, found 451.0373.
4.3. General procedure for the synthesis of benzofurans 3aes
4.3.5. N-[3-Acetyl-2-(methylthio)benzofuran-5-yl]-4-methylbenzene-
sulfonamide (3e). Yield: 42%; mp: 147e149 ꢂC; 1H NMR (400 MHz,
To a 50 mL round bottomed flaskcontainingN-(4-hydroxyphenyl)-
benzenesulfonamide (1 mmol) dissolved in 10 mL of acetonitrile was
added dropwise PhI(OAc)2 (483 mg, 1.5 mmol) in 5 mL of CH2Cl2 and
0.1 mL of 1 mol/L BF3$Et2O. After stirring at room temperature for
10 min, ketene S,S-acetals or N,S-acetals (1 mmol) and CuBr2 (4.6 mg,
0.02 mmol) were added and the solution was continued to stir, while
monitoring the reaction by TLC. After the completion of the reaction
(about 30 min), the solvent was evaporated under reduced pressure
and 20 mL of saturated sodium carbonate aqueous was added. CH2Cl2
was used to extract (3ꢁ20 mL), the combined organic layers were
washed with brine and dried over anhydrous MgSO4. The expected
benzofurans were obtained after column chromatography; elution
used a mixed solvent of petroleum ether and acetone.
DMSO-d6): d 2.31 (s, 3H, CH3), 2.48 (s, 3H, SCH3), 2.67 (s, 3H, COCH3),
6.99e7.01 (m, 1H, AreH), 7.32 (d, 2H, J¼8.0 Hz, AreH), 7.49 (d, 1H,
J¼8.8 Hz, AreH), 7.61 (d, 2H, J¼8.0 Hz, AreH), 7.62 (s,1H, AreH),10.20
(s, 1H, NH); 13C NMR (100 MHz, DMSO-d6):
d 13.7, 21.4, 31.1, 111.6,
113.0, 116.8, 117.8, 126.8, 127.3, 130.1, 135.0, 136.9, 143.6, 152.0, 163.8,
192.0;IR (KBr): n
3435, 3101, 2985, 2917,1706,1602 cmꢀ1;ESI-MS:m/z
373.8 [Mꢀ1]ꢀ, 375.9 [Mþ1]þ, 397.8 [MþNa]þ; HREI-MS (m/z) calcd
for C18H17NO4S2 (M) 375.0599, found 375.0603.
4.3.6. 5-(4-Methylphenylsulfonamido)-2-(methylthio)benzofuran-3-
carboxamide (3f). Yield: 35%; mp: 235e236 ꢂC; 1H NMR (400 MHz,
DMSO-d6):
d 2.29 (s, 3H, CH3), 2.58 (s, 3H, SCH3), 6.97 (d, 1H,
J¼8.8 Hz, AreH), 7.29 (d, 2H, J¼7.6 Hz, AreH), 7.42 (d, 1H, J¼8.8 Hz,
AreH), 7.58 (d, 2H, J¼8.0 Hz, AreH), 7.57 (s, 1H, AreH), 9.94 (s, 1H,
4.3.1. N-[3-(4-Methylbenzoyl)-2-(methylthio)benzofuran-5-yl]-4-
NH); 13C NMR (100 MHz, DMSO-d6):
d 15.2, 21.4, 111.5, 113.6, 118.6,
methyl-benzene-sulfonamide (3a). Yield: 61%; mp: 159e161 ꢂC; 1H
127.2, 130.0, 134.3, 137.0, 143.6, 152.1, 156.3, 164.3; IR (KBr): n 3449,
NMR (400 MHz, DMSO-d6):
d
2.33 (s, 3H, CH3), 2.44 (s, 3H, CH3),
3368, 2921, 1641 cmꢀ1; ESI-MS: m/z 375.0 [Mꢀ1]ꢀ, 377.0 [Mþ1]þ,
376.5 [MþNa]þ; HREI-MS (m/z) calcd for C17H16N2O4S2 (M)
376.0552, found 376.0557.
2.62 (s, 3H, SCH3), 7.01 (dd, 1H, J¼8.8 Hz, J¼2.0 Hz, AreH), 7.05 (d,
1H, J¼1.6 Hz, AreH), 7.31 (d, 2H, J¼8.8 Hz, AreH), 7.33 (d, 2H,
J¼8.8 Hz, AreH), 7.50 (d, 2H, J¼8.0 Hz, AreH), 7.52 (d, 1H, J¼8.8 Hz,
AreH), 7.56 (d, 2H, J¼8.0 Hz, AreH), 10.10 (s, 1H, NH); 13C NMR
4.3.7. N-[2-(Methylthio)-3-nitrobenzofuran-5-yl]-4-methyl-benze-
(100 MHz, DMSO-d6):
d
14.1, 21.4, 21.7,111.8,112.8,116.7,118.3,127.1,
nesulfonamide (3g). Yield: 61%; mp: 193e195 ꢂC; 1H NMR

C.-W. Yang et al. / Tetrahedron 68 (2012) 10201e10208
10207
(400 MHz, DMSO-d6):
d
2.31 (s, 3H, CH3), 2.76 (s, SCH3), 7.14 (d, 1H,
1.62e1.67 (m, 2H, CH2CH3), 2.33 (s, 3H, CH3), 3.45e3.47 (m, 2H,
NHCH2), 6.49 (s, 1H, AreH), 7.14 (d, 1H, J¼8.4 Hz, AreH), 7.23e7.56
(m, 9H, AreH), 9.13 (t, 1H, J¼6.0 Hz, NHCH2), 9.93 (s, 1H, NHSO2);
J¼8.0 Hz, AreH), 7.33e7.71 (m, 6H, AreH), 10.42 (s, 1H, NH); 13C
NMR (100 MHz, DMSO-d6):
d 13.5, 21.4, 111.0, 112.5, 118.7, 121.6,
127.2, 128.8, 130.1, 136.3, 136.8, 143.8, 150.6, 165.8; IR (KBr):
n
3435,
13C NMR (100 MHz, DMSO-d6):
d 11.5, 21.4, 23.2, 43.8, 92.7, 110.8,
3241, 1599 cmꢀ1; ESI-MS: m/z 376.6 [Mꢀ1]ꢀ; HREI-MS (m/z) calcd
111.0, 115.2, 127.0, 127.1, 129.1, 129.2, 129.9, 134.4, 135.6, 137.0, 139.9,
for C16H14N2O5S2 (M) 378.0344, found 378.0351.
143.4, 146.1, 166.9, 186.8; IR (KBr): n 3438, 3171, 2963, 1648,
1593 cmꢀ1; ESI-MS: m/z 480.8 [Mꢀ1]ꢀ, 483.0 [Mþ1]þ, 504.9
[MþNa]þ, 520.9 [MþK]þ; HREI-MS (m/z) calcd for C25H23N2O4SCl
(M) 482.1067, found 482.1073.
4.3.8. N-[3-Cyano-2-(methylthio)benzofuran-5-yl]-4-methylbenzene-
sulfonamide (3h). Yield: 63%; mp: 184e186 ꢂC; 1H NMR (400 MHz,
DMSO-d6):
d
2.32 (s, 3H, CH3), 2.76 (s, SCH3), 7.12 (dd, 1H, J¼2.0 Hz,
8.8 Hz, AreH), 7.24 (d, 1H, J¼1.6 Hz, AreH), 7.35 (d, 2H, J¼8.4 Hz,
4.3.13. N-[3-Acetyl-2-(propylamino)benzofuran-5-yl]-4-methylben-
AreH), 7.57e7.60 (m, 3H, AreH), 10.39 (s, 1H, NH); 13C NMR
zenesulfonamide (3m). Yield: 58%; mp: 240e241 ꢂC; 1H NMR
(100 MHz, DMSO-d6):
d
15.2, 21.4, 111.0, 112.7, 112.9, 119.4, 126.9,
(400 MHz, DMSO-d6):
d
0.92 (t, 3H, J¼7.2 Hz, CH2CH3), 1.54e1.63
127.2, 127.3, 130.2, 135.7, 136.7, 143.8, 151.6, 164.5; IR (KBr):
n
3450,
(m, 2H, CH2CH3), 2.27 (s, 3H, CH3), 2.30 (s, 3H, CH3), 3.34e3.41 (m,
2H, NHCH2), 6.73 (dd, 1H, J¼8.4 Hz, 2.0 Hz, AreH), 7.16 (d, 1H,
J¼2.0 Hz, AreH), 7.21 (d, 1H, J¼8.4 Hz, AreH), 7.32 (d, 2H, J¼8.4 Hz,
AreH), 7.62 (d, 2H, J¼8.4 Hz, AreH), 8.72 (t, 1H, J¼6.0 Hz, AreH),
3241, 2922, 1623 cmꢀ1; ESI-MS: m/z 357.0 [Mꢀ1]ꢀ, 359.0 [Mþ1]þ,
381.0 [MþNa]þ; HREI-MS (m/z) calcd for C17H14N2O3S2 (M)
358.0446, found 358.0450.
10.01 (s, 1H, NH); 13C NMR (100 MHz, DMSO-d6):
d 11.4, 21.4, 23.3,
4.3.9. N-[3-(4-Methylbenzoyl)-2-(propylamino)benzofuran-5-yl]-4-
29.3, 43.6, 93.5, 110.7, 111.2, 114.5, 127.3, 127.7, 130.0, 134.7, 143.5,
methyl-benzene sulfonamide (3i). Yield: 55%; mp: 204e205 ꢂC; 1H
146.0, 165.4, 190.1; IR (KBr): n ;
3435, 3240, 2968, 1667, 1490 cmꢀ1
NMR (400 MHz, DMSO-d6):
d
0.92 (t, 3H, J¼7.6 Hz, CH2CH3),
EI-MS: m/z 386 [M]þ; HREI-MS (m/z) calcd for C20H22N2O4S (M)
386.1300, found 386.1306.
1.62e1.67 (m, 2H, CH2CH3), 2.33 (s, 3H, CH3), 2.44 (s, 3H, CH3),
3.43e3.48 (m, 2H, NHCH2), 6.62 (s, 1H, AreH), 6.68 (dd, 1H,
J¼8.8 Hz, 1.6 Hz, AreH), 7.23 (d, 1H, J¼8.8 Hz, AreH), 7.29e7.31 (m,
4H, AreH), 7.40 (d, 2H, J¼8.0 Hz, AreH), 7.44 (d, 2H, J¼8.0 Hz,
AreH), 9.12 (t, 1H, J¼6.0 Hz, NHCH2), 9.87 (s, 1H, NHSO2); 13C NMR
4.3.14. N-[3-Nitro-2-(propylamino)benzofuran-5-yl]-4-methyl-ben-
zenesulfonamide (3n). Yellowish powder, yield: 47%; mp:
199e201 ꢂC; 1H NMR (400 MHz, DMSO-d6):
d
0.89 (t, 3H, J¼7.6 Hz,
(100 MHz, DMSO-d6):
d
11.5, 21.4, 21.7, 23.3, 43.7, 92.7, 110.7, 111.6,
CH2CH3), 1.61e1.70 (m, 2H, CH2CH3), 2.31 (s, 3H, CH3), 3.44e3.49
(m, 2H, NHCH2), 6.92 (dd, 1H, J¼8.8 Hz, 2.0 Hz, AreH), 7.32e7.63
(m, 6, AreH), 9.59 (t, 1H, J¼6.4 Hz, NH), 10.21 (s, 1H, SO2NH); 13C
115.3, 127.2, 127.3, 127.5, 129.4, 129.9, 134.2, 137.0, 138.4, 140.8,
143.4, 146.1, 166.9, 188.2; IR (KBr):
n 3436, 3291, 3166, 2963, 1644,
1592 cmꢀ1; ESI-MS: m/z 460.9 [Mꢀ1]ꢀ, 462.9 [Mþ1]þ, 484.9
[MþNa]þ; HREI-MS (m/z) calcd for C26H26N2O4S (M) 462.1613,
found 462.1620.
NMR (100 MHz, DMSO-d6): d 11.4, 21.4, 22.8, 44.6, 109.1, 111.2, 111.3,
116.8, 122.8, 122.7, 127.2, 130.1, 135.6, 137.0, 143.6, 144.2, 161.0; IR
(KBr):
n
3433, 3242, 2965, 1665, 1494, 1468, 1158, 1078 cmꢀ1; ESI-
MS: m/z, 411.9 [MþNa]þ; HREI-MS (m/z) calcd for C18H19N3O5S
4.3.10. N-[3-(4-Methoxybenzoyl)-2-(propylamino)benzofuran-5-yl]-
(M) 389.1045, found 389.1051.
4-methyl-benzenesulfonamide (3j). Yellowish powder, yield: 72%;
mp: 86e88 ꢂC; 1H NMR (400 MHz, DMSO-d6):
d
0.92 (t, 3H,
4.3.15. N-[2-(Benzylamino)-3-(4-methylbenzoyl)benzofuran-5-yl]-4-
J¼7.2 Hz, CH2CH3), 1.62e1.67 (m, 2H, CH2CH3), 2.33 (s, 3H, CH3),
3.45 (q, 2H, J¼7.2 Hz, NHCH2), 3.88 (s, 3H, OCH3), 6.68 (d, 1H,
J¼2.0 Hz, AreH), 6.72 (dd, 1H, J¼6.8 Hz, 2.0 Hz, AreH), 7.01 (d, 2H,
J¼8.8 Hz, AreH), 7.24 (d, 1H, J¼8.4 Hz, AreH), 7.30 (d, 2H, J¼8.0 Hz,
AreH), 7.46 (d, 2H, J¼7.2 Hz, AreH), 7.48 (d, 2H, J¼7.2 Hz, AreH),
9.07 (t, 1H, J¼7.2 Hz, NHCH2), 9.87 (s, 1H, NHSO2); 13C NMR
methyl-benzenesulfonamide (3o). Yellowish powder. Yield: 73%;
mp: 189e189 ꢂC; 1H NMR (400 MHz, DMSO-d6):
d 2.33 (s, 3H, CH3),
2.44 (s, 3H, CH3), 4.69 (d, 2H, J¼7.2 Hz, NHCH2), 6.63 (s, 1H, AreH),
6.68 (dd, 1H, J¼8.8 Hz, 2.0 Hz, AreH), 7.22 (d, 1H, J¼8.8 Hz, AreH),
7.26e7.44 (m, 13H, AreH), 9.51 (t, 1H, J¼7.2 Hz, NH), 9.87 (s, 1H,
NH); 13C NMR (100 MHz, DMSO-d6):
d 21.4, 21.7, 45.6, 93.0, 110.8,
(100 MHz, DMSO-d6):
d
11.5, 21.4, 23.3, 43.7, 55.8, 92.5, 110.7, 111.7,
111.7, 115.4, 127.1, 127.5, 127.8, 129.0, 129.1, 129.4, 129.9, 130.0, 134.3,
114.1, 115.2, 127.2, 127.4, 129.5, 129.9, 133.5, 134.2, 137.0, 143.4, 146.1,
137.0, 138.4, 138.8, 140.9, 141.0, 143.4, 146.1, 187.6; IR (KBr): n 3434,
161.6, 166.8, 187.5; IR (KBr):
n
3438, 3158, 2961, 1643, 1603 cmꢀ1
;
3249, 2921, 1643, 1182 cmꢀ1; ESI-MS: m/z 508.8 [Mꢀ1]ꢀ, 511.0
[Mþ1]þ, 533.0 [MþNa]þ, 548.9 [MþK]þ; HREI-MS (m/z) calcd for
C30H26N4O4S (M) 510.1613, found 510.1618.
ESI-MS: m/z 476.8 [Mꢀ1]ꢀ, 479.0 [Mþ1]þ, 501.0 [MþNa]þ, 516.9
[MþK]þ; HREI-MS (m/z) calcd for C26H26N2O5S (M) 478.1562, found
478.1568.
4.3.16. N-[2-(Benzylamino)-3-(4-methoxybenzoyl)benzofuran-5-yl]-
4.3.11. N-[3-Benzoyl-2-(propylamino)benzofuran-5-yl]-4-
4-methyl-benzenesulfonamide (3p). Yellowish powder. Yield: 76%;
methylbenzenesulfonamide (3k). Yield: 54%; mp: 191e192 ꢂC; 1H
mp: 168e170 ꢂC; 1H NMR (400 MHz, DMSO-d6):
d 2.32 (s, 3H, CH3),
NMR (400 MHz, DMSO-d6):
d
0.92 (t, 3H, J¼7.6 Hz, CH2CH3),
3.88 (s, 3H, OCH3), 4.69 (d, 2H, J¼6.4 Hz, CH2Ph), 6.68e6.72 (m, 2H,
AreH), 7.00 (d, 2H, J¼8.8 Hz, AreH), 7.22 (d, 1H, J¼8.4 Hz, AreH),
7.25e7.40 (m, 7H, AreH), 7.45 (d, 2H, J¼8.4 Hz, AreH), 7.49 (d, 2H,
J¼8.8 Hz, AreH), 9.45 (t, 1H, J¼6.4 Hz, NHCH2), 9.87 (s, 1H, NHSO2);
1.61e1.70 (m, 2H, CH2CH3), 2.33 (s, 3H, CH3), 3.47e3.49 (m, 2H,
NHCH2), 6.57 (d, 1H, J¼1.6 Hz, AreH), 6.68 (dd, 1H, J¼8.8 Hz,
J¼1.6 Hz, AreH), 7.24 (d, 1H, J¼8.8 Hz, AreH), 7.29 (d, 2H, J¼8.0 Hz,
AreH), 7.43 (d, 2H, J¼8.8 Hz, AreH), 7.47e7.63 (m, 5H, AreH), 9.16
(t, 1H, J¼6.0 Hz, NHCH2), 9.89 (s, 1H, NHSO2); 13C NMR (100 MHz,
13C NMR (100 MHz, DMSO-d6):
d 21.4, 45.6, 55.8, 92.9, 108.8, 110.7,
111.7, 115.4, 127.1, 127.5, 127.8, 128.1, 129.1, 129.4, 129.9, 134.3, 137.0,
DMSO-d6):
d
11.5, 21.4, 23.2, 43.8, 92.3, 110.7, 111.4, 115.3, 127.1,
138.4, 138.8, 140.9, 141, 143.4, 146.1, 187.6; IR (KBr): n 3434, 2924,
127.2,128.5,129.0,129.9,131.0,134.3,137.0,141.3,143.4,146.1,166.9,
1644, 1602 cmꢀ1
;
m/z 524.8 [Mꢀ1]ꢀ, 527.0 [Mþ1]þ, 549.0
188.3; IR (KBr):
n
3435, 3099, 2929, 1648, 1593 cmꢀ1; ESI-MS: m/z
[MþNa]þ; HREI-MS (m/z) calcd for C30H26N2O5S (M) 526.1562,
449.0 [Mþ1]þ, 471.0 [MþNa]þ, 486.9 [MþK]þ; HREI-MS (m/z) calcd
found 526.1570.
for C25H24N2O4S (M) 448.1457, found 448.1464.
4.3.17. N-[2-(Benzylamino)-3-(4-chlorobenzoyl)benzofuran-5-yl]-4-
4.3.12. N-[3-(4-Chlorobenzoyl)-2-(propylamino)benzofuran-5-yl]-4-
methyl-benzenesulfonamide (3q). Yellowish powder. Yield: 64%;
methylbenzene-sulfonamide (3l). Yield: 49%; mp: 161e163 ꢂC; 1H
mp: 109e111 ꢂC; 1H NMR (400 MHz, DMSO-d6):
d
2.32 (s, 3H,
NMR (400 MHz, DMSO-d6):
d
0.91 (t, 3H, J¼7.2 Hz, CH2CH3),
CH2CH3), 4.70 (s, 2H, NHCH2), 6.50 (s, 1H, AreH), 6.71 (d, 2H,

10208
C.-W. Yang et al. / Tetrahedron 68 (2012) 10201e10208
J¼7.6 Hz, AreH), 7.22e7.54 (m, 14H, AreH), 9.55 (s, 1H, NH), 9.93 (s,
1H, NH); 13C NMR (100 MHz, DMSO-d6):
21.4, 45.6, 93.0, 110.9,
111.2, 115.3, 127.1, 127.8, 127.8, 129.0, 129.0, 129.1, 129.3, 129.9, 134.5,
References and notes
d
1. (a) Mendonca, P. P.; Araujo, A. R.; Young, M. C. M.; Giesbrecht, A. M. Phyto-
chemistry 2000, 55, 597e601; (b) Sheen, W. S.; Tsai, I. L.; Teng, C. M.; Chen, I. S.
Phytochemistry 1994, 36, 213e215; (c) Shikishima, Y.; Takaishi, Y.; Honda, G.; Ito,
M.; Takeda, Y.; Kodzhimatov, O. K.; Ashurmetov, O.; Le, K. H. Chem. Pharm. Bull.
2001, 49, 877e880.
2. (a) Hwu, J. R.; Chuang, K. S.; Chuang, S. H.; Tsay, S. C. Org. Lett. 2005, 7,
1545e1548; (b) Jung, I.; Lee, J. K.; Song, K. H.; Song, K.; Kang, S. O.; Ko, J. J. Org.
Chem. 2007, 72, 3652e3658; (c) Zhang, F. M.; Yun, G. L.; Zhang, J. M.; Yang, C. D.
Chin. J. Liquid Crystals and Displays 2010, 1, 5e10 (in Chinese).
3. (a) Benitez, A.; Herrera, F. R.; Romero, M.; Talamas, F. X.; Muchowski, J. M. J. Org.
Chem. 1996, 61, 1487e1492; (b) Asao, N.; Aikawa, H. J. Org. Chem. 2006, 71,
5249e5253.
135.7, 137.0, 138.7, 139.8, 143.4, 146.1, 166.5, 187.1; IR (KBr):
n 3434,
3256, 2922, 1643 cmꢀ1; ESI-MS: m/z 528.8 [Mꢀ1]ꢀ, 531.0 [Mþ1]þ,
552.7 [MþNa]þ; HREI-MS (m/z) calcd for C29H23N2O4SCl (M)
530.1067, found 530.1072.
4.3.18. N-[6-Methyl-3-(4-methylbenzoyl)-2-(methylthio)benzofuran-
5-yl]-4-methylbenzenesulfonamide (3r). Yellowish powder. Yield:
69%; mp: 199e201 ꢂC; 1H NMR (400 MHz, DMSO-d6):
d 2.06 (s, 3H,
4. (a) Lu, B.; Wag, B.; Zhang, Y. H.; Ma, D. W. J. Org. Chem. 2007, 72, 5337e5341; (b)
Mattson, E.; Scheidt, K. A. J. Am. Chem. Soc. 2007, 129, 4508e4509; (c) Duan, X.
F.; Zeng, J.; Zhang, Z. B.; Zi, G. F. J. Org. Chem. 2007, 72, 10283e10286.
5. Adams, R.; Whitaker, L. J. Am. Chem. Soc. 1956, 78, 658e660.
6. (a) Engler, T. A.; Combrink, K. D.; Letavic, M. A.; Lynch, K. O.; Ray, J. E., Jr. J. Org.
Chem. 1994, 59, 6567e6587; (b) Engler, T. A.; Wei, D.; Letavic, M. A.; Combrink,
K. D.; Reddy, J. P. J. Org. Chem. 1994, 59, 6588e6599.
7. Engler, T. A.; Meduna, S. P.; LaTessa, K. O.; Chai, W. J. Org. Chem. 1996, 61,
8598e8603.
8. (a) Engler, T. A.; Chai, W.; LaTessa, K. O. J. Org. Chem. 1996, 61, 9297e9308; (b)
Engler, T. A.; Scheibe, C. M. J. Org. Chem. 1998, 63, 6247e6253; (c) Engler, T. A.;
Wanner, J. J. Org. Chem. 2000, 65, 2444e2457.
CH3), 2.35 (s, 3H, CH3), 2.45 (s, 3H, CH3), 2.63 (s, 3H, CH3), 6.91 (s,
1H, AreH), 7.26 (d, 2H, J¼8.0 Hz, AreH), 7.33 (d, 2H, J¼8.0 Hz,
AreH), 7.41 (d, 2H, J¼8.0 Hz, AreH), 7.46 (s, 1H, AreH), 7.59 (d, 2H,
J¼8.0 Hz, AreH), 9.45 (s, 1H, NHSO2); 13C NMR (100 MHz, DMSO-
d6):
d 14.1, 18.5, 21.5, 21.7, 112.6, 116.7, 119.0, 124.8, 127.0, 128.9,
129.7, 129.9, 131.9, 132.0, 136.4, 138.0, 143.3, 153.4, 162.9, 189.2; IR
(KBr):
n
3435, 2920, 1623, 837 cmꢀ1; ESI-MS: m/z 464.0 [Mꢀ1]ꢀ,
466.0 [Mþ1]þ; HREI-MS (m/z) calcd for C25H23NO4S2 (M) 465.1068,
found 465.1065.
9. Liu, Y.-J.; Wang, M.; Yuan, H.-J.; Liu, Q. Adv. Synth. Catal. 2010, 352, 884e892.
ꢀ
ꢀ
10. (a) Tabakovic, I.; Grujic, Z.; Bejtovi&cacute, Z. J. Heterocycl. Chem. 1983, 20,
635e638; (b) Golabi, S. M.; Nematollahi, D. J. Electroanal. Chem. 1997, 420,
127e134; (c) Shamsipur, M.; Davarani, S. S. H.; Nematollahi, D. J. Heterocycl.
Chem. 2006, 43, 1673e1677; (d) Fakhari, A. R.; Nematollahi, D.; Shamsipur, M.;
Makarem, S.; Davarani, S. S. H.; Alizadeh, A.; Khavasi, H. R. Tetrahedron 2007, 63,
3894e3898; (e) Zeng, C. C.; Liu, F. J.; Ping, D. W.; Hu, L. M.; Cai, Y. L.; Zhong, R. G.
J. Org. Chem. 2009, 74, 6386e6389; (f) Zeng, C. C.; Ping, D. W.; Xu, Y. S.; Hu, L.
4.3.19. N-[6-Methyl-3-(4-methylbenzoyl)-2-(propylamino)benzofu-
ran-5-yl]-4-methylbenzenesulfonamide (3s). Yellowish powder.
Yield: 64%; mp: 194e197 ꢂC; 1H NMR (400 MHz, DMSO-d6):
d 0.93
(t, 3H, J¼7.2 Hz, CH2CH3), 1.61e1.71 (m, 2H, CH2CH3), 2.06 (s, 3H,
CH3), 2.02 (s, 3H, CH3), 2.37 (s, 3H, CH3), 2.43 (s, 3H, CH3), 3.45e3.50
(m, 2H, NHCH2), 6.53 (s,1H, AreH), 7.20 (s,1H, AreH), 7.22e7.41 (m,
8H, AreH), 9.15 (t, 2H, J¼6.4 Hz, AreH), 9.23 (s, 1H, NHSO2); 13C
M.; Zhong, R. G. Eur. J. Org. Chem. 2009,
5832e5840.
ꢀ
11. For the application of hypevalent iodine, see review: (a) Pouysegu, L.; Deffieux,
D.; Quideau, S. Tetrahedron 2010, 66, 2235e2261; (b) Richardson, R. D.; Wirth, T.
Angew. Chem., Int. Ed. 2006, 45, 4402e4404; (c) Zhdankin, V. V.; Stang, P. J.
Chem. Rev. 2008, 108, 5299e5358.
NMR (100 MHz, DMSO-d6):
d 11.6, 18.3, 21.5, 21.6, 23.3, 43.8, 92.4,
112.0, 117.7, 124.7, 127.0, 127.5, 129.0, 129.3, 129.8, 131.2, 138.1, 138.4,
12. Huang, Z. T.; Zhang, P. C. Synth. Commun. 1990, 20, 1399e1407.
13. (a) Yin, Y.-B.; Zhang, Q.; Liu, Q.; Liu, Y.; Sun, S.-G. Synth. Commun. 2007, 37,
703e711; (b) Rao, H. S. P.; Sakthikumar, L.; Vanitha, S.; Kumar, S. S. Tetrahedron
Lett. 2003, 44, 4701e4704.
14. (a) Kumar, A.; Aggarwal, V.; Ila, H.; Junjappa, H. Synthesis 1980, 748e751; (b)
Singh, O. M.; Junjappa, H.; Ila, H. J. Chem. Soc., Perkin Trans. 1 1997, 23,
3561e3565.
15. For a nice review about SNV reaction, see: Bernasconi, C. F.; Rappoport, Z. Acc.
Chem. Res. 2009, 42, 993e1003 recent examples, see (a) Chikhalikar, S.; Bhawe,
V.; Ghotekar, B.; Jachak, M.; Ghagare, M. J. Org. Chem. 2011, 76, 3829e3836; (b)
Bella, M.; Schultz, M.; Milata, V. ARKIVOC 2012, 242e251; (c) Ibis, C.; Tuyun, A.
F. Curr. Org. Synth. 2011, 8, 861e871.
16. Jackson, S. K.; Banfield, S. C.; Kerr, M. A. Org. Lett. 2005, 7, 1215e1218.
17. Zhang, T.; Jia, Y.-M.; Yan, S.-J.; Yu, C.-Y.; Huang, Z.-T. ARKIVOC 2009, 156e170.
18. Reddy, T. I.; Bhawal, B. M.; Rajappa, S. Tetrahedron 1993, 49, 2101e2108.
19. (a) Kumar, A.; Aggarwal, V.; ILa, H.; Junjappa, H. Synthesis 1980, 748e751; (b)
Gupta, A. K.; ILa, H.; Junjappa, J. Synthesis 1988, 284e286.
140.7, 143.1, 147.5, 166.8, 187.8; IR (KBr):
n 3450, 3288, 2970,
1641 cmꢀ1; ESI-MS: m/z 475.0 [Mꢀ1]ꢀ, 477.1 [Mþ1]þ, 499.0
[MþNa]þ; HREI-MS (m/z) calcd for C27H28N2O4S (M) 478.1770,
found 478.1767.
Acknowledgements
This work was supported by grants from the National Basic
Research Program of China (No. 2009CB930200), The National Key
Technology R&D Program (2011BAD23B01), Beijing Natural Science
Foundation (No. 7112008) and Beijing City Education Committee
(KM201010005009). We also thank Mrs. Jinchao Wei in Institute of
Chemistry, CAS, for the HREI-MS measurement.