Novel syntheses of 2,3-dihydro-5H-1,4-benzoxathiepins using polymer-supported bis(trifluoroacetoxyiodo)benzene

Article abstract of DOI:10.1002/jccs.200400153

Pummerer-type reaction was carried out with α-acylsulfides and polymer-supported bis(trifluoroacetoxyiodo)benzene (PSBTI) instead of α-acylsulfoxides to prepare 2,3-dihydro-5H-1,4-benzoxathiepins.

Full text of DOI:10.1002/jccs.200400153

Journal of the Chinese Chemical Society, 2004, 51, 1025-1028
1025
Novel Syntheses of 2,3-Dihydro-5H-1,4-benzoxathiepins Using
Polymer-supported bis(trifluoroacetoxyiodo)benzene
a
b
Hsin-Yu Huang (
Rei-Sheu Hou (
), Huey-Min Wang (
),
b
a
) and Ling-Ching Chen * (
)
Graduate Institute of Pharmaceutical Sciences, Kaohsiung Medical University,
a
Kaohsiung 807, Taiwan, R.O.C.
b
Chung Hwa College of Medical Technology, Tainan 717, Taiwan, R.O.C.
Pummerer-type reaction was carried out with a-acyl sulfides and polymer-supported bis(trifluoroaceto-
xyiodo)benzene (PSBTI) instead of a-acyl sulfoxides to prepare 2,3-dihydro-5H-1,4-benzoxathiepins.
Keywords: Pummerer rearrangement; Polymer-supported bis(trifluoroacetoxyiodo)benzene;
2
,3-Dihydro-5H-1,4-benzoxathiepins.
INTRODUCTION
(PSBTI) shows similar reactivity to BTI and have utilized it
as a replacement for previously reported iodine(III) reagents.
In this work, Pummerer-type reaction of a-acyl sulfides us-
ing PSBTI was applied to prepare 2,3-dihydro-5H-1,4-ben-
The Pummerer rearrangement of sulfoxides with acid
anhydrides is a useful method for the synthesis of a-substi-
tuted sulfides and has attracted considerable attention from
7
zoxathiepins.
1
both synthetic and mechanistic points of view.
In recent years, hypervalent iodine(III) reagents have
been used extensively in organic syntheses due to their low
RESULTS AND DISCUSSION
2
toxicity, ready availability, and easy handling. As a continu-
ation of our studies concerning hypervalent iodine(III) chem-
istry, we have reported a modified Pictet-Spengler cycliza-
tion of N-sulfonyl-b-phenethylamines with ethyl methylthio-
acetate using bis(trifluoroacetoxyiodo)benzene (BTI) to pre-
The requisite ethyl(2-phenoxyethylthio)acetate (2) was
readily prepared from 2-phenoxybromoethane (1) with ethyl-
2 3
mercaptoacetate and K CO in acetone. Treatment of 2 with
PSBTI and trifluoroacetic acid (TFA) in dichloroethane
(DCE) caused cyclization to give 2,3-dihydro-5H-1,4-benzo-
xathiepins (3) in moderate yields (Scheme I).
3
pare ethyl 1,2,3,4-tetrahydroisoquinoline-1-carboxylates.
4
5
6
Recently, Togo et al., Ley et al. and Kita et al. demonstrated
that polymer-supported bis(trifluoroacetoxyiodo)benzene
The recovery and recycling of the resin (polyiodo-
Scheme I
R1
R2
O
R1
R2
O
O
R1
R2
A
B
Br
S
S
R3
R3 CO Et
R3 CO Et
2
2
1
3
2
a, R = R = R = H
1
2
3
b, R = R = H, R = CH
3
1
3
2
c, R = R = H, R = OCH
3
1
3
2
d, R = R = CH , R = H
1
3
3
2
e, R = R = OCH , R = H
1
3
3
2
Reagents: A) HSCH CO Et/K CO /CH COCH
3
2
2
2
3
3
B) PSBTI-TFA/DCE

1
026 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
Huang et al.
Scheme II
R1
R2
O
R1
R2
O
I(OCOCF3)
2
_
OCOCF3
+
S
S
I
I
R3
CO Et
R3
2
CO Et OCOCF3
2
2
4
R1
O
O
R1
R2
_
+
S
R2
OCOCF3
S
R3
CO Et
2
R3 CO Et
2
5
3
styrene) are easy. After quenching with saturated aqueous
NaHCO , the resin was recovered nearly quantitatively by fil-
to prepare 2,3-dihudro-5H-1,4-benzoxathiepins.
3
tering the resulting mixture. The recovered resin was easily
reoxidized to PSBTI via polymer-supported (diacetoxy-
EXPERIMENTAL SECTION
8
iodo)benzene (PSDIB) by heating in CF
3
CO
2
H at 70 °C, fol-
lowed by precipitation by Et
2
O. Thus, PSBTI can be used re-
All melting points are uncorrected. The IR spectra were
1
peatedly without loss of activity. A possible pathway of the
cyclization is illustrated in Scheme II. The cyclization is as-
sumed to proceed through Pummerer-type reaction interme-
diate (5) which would be formed by attack of PSBTI on the
sulfur atom of 2, followed by simultaneous elimination of the
a-hydrogen and polyiodobenzene from the resultant sulfon-
ium salt (4), as shown in Scheme II.
recorded on a Shimadzu IR-27 G spectrophotometer. H
1
3
NMR and C NMR spectra were recorded on a Varian Unity
Plus 400 MHz. Chemical shifts were measured in ppm (d)
with respect to TMS. MS were obtained on a JEOL JMS D-
300 instrument.
General procedure for the preparation of 3a-e, 7 and 9
To a solution of the sulfide (2) (1 mmol) and PSBTI (1.5
mmol) in DCE (5 mL) was added TFA (2 mmol) in DCE (5
mL), and the mixture was stirred at room temperature for 10
min. Then the mixture was refluxed for 3 h to complete the re-
action. After cooling, the resultant mixture was quenched
Similarly, treatment of sulfides 6 and 8 with PSBTI and
TFA in DCE caused cyclization to give the corresponding
1
,4-benzoxathithipin derivatives 7 and 9 in moderate yields
(
Scheme III).
Scheme III
with water and extracted with CH
washed with saturated aqueous NaHCO
over MgSO , and concentrated under reduced pressure, and
2
Cl
2
. The extract was
3
and brine, dried
O
S
O
4
S
the residue was purified by chromatography on a silica gel
PSBTI-TFA
DCE
CO Et
2
CO Et
2
column, eluting with benzene-chloroform to give 3a-e, 7 and
9
.
6
7
S
S
EtO2C
EtO2C
5-Carboethoxy-2,3-dihydro-5H-1,4-benzoxathiepin (3a)
mp 77-78 °C (AcOEt-n-hexane), yield 45% IR (KBr) u
O
O
PSBTI-TFA
DCE
-
1 1
1727 cm ; H NMR (CDCl
3
) d: 1.27 (t, J = 7.2 Hz, 3H), 2.90-
3
4
.25 (m, 2H), 4.14-4.31 (m, 2H), 4.28 (q, J = 7.2 Hz, 2H),
8
9
1
3
3
.74 (s, 1H), 7.07-7.26 (m, 4H); C NMR (100 MHz, CDCl )
In conclusion, our results here demonstrate that poly-
d: 14.1, 32.7, 49.5, 55.6, 61.9, 73.1, 113.5, 114.7, 116.0,
123.4, 152.1, 156.0, 169.5; EI-MS m/z (relative intensity)
mer-support bis(trifluoroacetoxyiodo)benzene (PSBTI) is a
+
useful reagent for Pummerer-type reaction of a-acyl sulfides
238 (M ), 179, 165, 137, 131, 77, 51, 49. Anal. Calcd for

Syntheses of 2,3-Dihydro-5H-1,4-benzoxathiepins
J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004 1027
C
12
H
14
O
3
S: C, 60.48; H, 5.92. Found: C, 60.72; H, 6.12.
6.23.
5
-Carboethoxy-7-methyl-2,3-dihydro-5H-1,4-benzoxa-
thiepin (3b)
mp 95-96 °C (AcOEt-n-hexane), yield 42% IR (KBr) u
7-Carboethoxy-9,10-dihydro-7H-11-oxa-8-thia-cyclohep-
tanaphthalene (7)
mp 107-108 °C (AcOEt-n-hexane), yield 43% IR (KBr)
-
1
1
-1 1
1
729 cm ; H NMR (CDCl
3
) d: 1.28 (t, J = 7.2 Hz, 3H), 2.29
3
u 1726 cm ; H NMR (CDCl ) d: 1.26 (t, J = 7.2 Hz, 3H),
(
s, 3H), 2.88-3.23 (m, 2H), 4.10-4.28 (m, 2H), 4.26 (q, J = 7.2
2.96-3.40 (m, 2H), 4.23-4.45 (m, 2H), 4.27 (q, J = 7.2 Hz,
1
3
13
Hz, 2H), 4.68 (s, 1H), 6.93-7.03 (m, 3H); C NMR (100
MHz, CDCl ) d: 14.1, 32.7, 49.5, 55.6, 61.9, 73.1, 113.5,
14.7, 116.0, 123.4, 152.1, 156.0, 169.5; EI-MS m/z (relative
2H), 4.90 (s, 1H), 7.28-8.16 (m, 6H); C NMR (100 MHz,
3
3
CDCl ) d: 14.0, 32.5, 49.5, 61.9, 71.5, 121.8, 124.2, 125.4,
1
126.2, 126.3, 127.6, 128.2, 134.2, 153.6, 169.6; EI-MS m/z
+
+
intensity) 252 (M ), 193, 179, 151, 145, 105, 91, 65, 45. Anal.
Calcd for C13 S: C, 61.88; H, 6.39. Found: C, 62.05; H,
(relative intensity) 288 (M ), 215, 187, 169, 127, 115, 77, 59.
H
16
O
3
Anal. Calcd for C16
66.48; H, 5.68.
16 3
H O S: C, 66.64; H, 5.59. Found: C,
6
.14.
5
-Carboethoxy-7-methoxy-2,3-dihydro-5H-1,4-benzoxa-
11-Carboethoxy-8,9-dihydro-11H-7-oxa-10-thia-cyclohep-
tanaphthalene (9)
thiepin (3c)
mp 84-85 °C (AcOEt-n-hexane), yield 40% IR (KBr) u
mp 111-112 °C (AcOEt-n-hexane), yield 38% IR (KBr)
-
1
1
-1 1
1
3
731 cm ; H NMR (CDCl
3
) d: 1.27 (t, J = 7.2 Hz, 3H), 2.88-
3
u 1726 cm ; H NMR (CDCl ) d: 1.18 (t, J = 7.2 Hz, 3H),
.25 (m, 2H), 3.76 (s, 3H), 4.03-4.22 (m, 2H), 4.25 (q, J = 7.2
2.60-3.48 (m, 2H), 4.00-4.64 (m, 2H), 4.21 (q, J = 7.2 Hz,
1
3
13
Hz, 2H), 4.68 (s, 1H), 6.68-7.00 (m, 3H); C NMR (100
MHz, CDCl ) d: 14.1, 32.7, 49.5, 55.6, 61.9, 73.1, 113.5,
14.7, 116.0, 123.4, 152.1, 156.0, 169.5; EI-MS m/z (relative
2H), 5.32 (s, 1H), 7.22-7.92 (m, 6H); C NMR (100 MHz,
3
3
CDCl ) d: 14.1, 30.4, 43.1, 62.0, 71.4, 122.3, 124.8, 127.1,
1
127.3, 128.9, 129.9, 131.4, 155.6, 170.0; EI-MS m/z (relative
+
+
intensity) 268 (M ), 209, 195, 163, 149, 121, 91, 77. Anal.
Calcd for C13 S: C, 58.19; H, 6.01. Found: C, 58.31; H,
intensity) 288 (M ), 215, 187, 169, 127, 115, 77, 59. Anal.
H
16
O
4
Calcd for C16
5.63.
16 3
H O S: C, 66.64; H, 5.59. Found: C, 66.42; H,
5
.94.
5
-Carboethoxy-6,8-dimethyl-2,3-dihydro-5H-1,4-benzoxa-
thiepin (3d)
mp 105-106 °C (AcOEt-n-hexane), yield 64% IR (KBr)
ACKNOWLEDGEMENT
-
1 1
u 1726 cm ; H NMR (CDCl
3
) d: 1.21 (t, J = 7.2 Hz, 3H),
.27 (s, 3H), 2.32 (s, 3H), 2.54-3.40 (m, 2H), 3.84-4.53 (m,
H), 4.19 (q, J = 7.2 Hz, 2H), 4.69 (s, 1H), 6.71 (s, 1H), 6.80
We gratefully acknowledge the National Science Coun-
cil of the Republic of China for the financial support of this
work (Grant No. 92-2113-M-037-014).
2
2
1
3
(
s, 1H); C NMR (100 MHz, CDCl
3
) d: 14.1, 19.7, 20.9,
3
1
1
0.3, 44.2, 61.7, 72.4, 120.8, 127.4, 135.3, 138.6, 157.6,
+
69.9; EI-MS m/z (relative intensity) 266 (M ), 207, 193,
65, 147, 119, 91, 77. Anal. Calcd for C14 S: C, 63.13;
Received January 13, 2004.
18 3
H O
H, 6.81. Found: C, 63.35; H, 6.68.
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5
-Carboethoxy-6,8-dimethoxy-2,3-dihydro-5H-1,4-benzo-
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mp 81-82 °C (AcOEt-n-hexane), yield 61% IR (KBr) u
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1 1
1
3
4
732 cm ; H NMR (CDCl
3
) d: 1.24 (t, J = 7.2 Hz, 3H), 2.62-
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NMR (100 MHz, CDCl
3
7
+
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H O

1
028 J. Chin. Chem. Soc., Vol. 51, No. 5A, 2004
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