Thermal reactions of β-hydroxysulfides bearing benzothiazole: Sulfenic acid trapping via a spiro intermediate

Article abstract of DOI:10.1080/10426501003773480

Benzothiazolyl 2-hydroxyethyl sulfoxide (1a) was found to afford bis[2-(2-oxobenzotiazolyl)-ethyl] disulfide (2a) in the presence of DBU at rt. 2a was formed by the condensation of corresponding sulfenic acid intermediate. Thermolyses of 1a in the presence of ethyl propiolate at 60-140C were carried out to succeed to trap sulfenic acid 6a as an intermediate. Trapping of 2-benzothiazolyloxyenthanesulfenic acid (6a) revealed that the thermal reaction proceeded via a five-membered spiro intermediate 5a. Copyright Taylor & Francis Group.

Full text of DOI:10.1080/10426501003773480

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Phosphorus, Sulfur, and Silicon and the
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Thermal Reactions of β-Hydroxysulfides
Bearing Benzothiazole: Sulfenic Acid
Trapping via a Spiro Intermediate
Nobuhiko Yamada a , Takanori Koyasu a , Mayumi Sonami a , Michiko
Aoi a , Shintaro Tashiro a , Md. Chanmiya Sheikh a , Yusuke Ishida a ,
Wataru Kawashima a , Toshiaki Yoshimura b & Hiroyuki Morita a
a Department of Material Systems Engineering and Life Science,
Faculty of Engineering , University of Toyama , Japan
b Department of Environmental Applied Chemistry, Faculty of
Engineering , University of Toyama , Japan
Published online: 27 May 2010.
To cite this article: Nobuhiko Yamada , Takanori Koyasu , Mayumi Sonami , Michiko Aoi , Shintaro
Tashiro , Md. Chanmiya Sheikh , Yusuke Ishida , Wataru Kawashima , Toshiaki Yoshimura & Hiroyuki
Morita (2010) Thermal Reactions of β-Hydroxysulfides Bearing Benzothiazole: Sulfenic Acid Trapping
via a Spiro Intermediate, Phosphorus, Sulfur, and Silicon and the Related Elements, 185:5-6,
1142-1153, DOI: 10.1080/10426501003773480
To link to this article: http://dx.doi.org/10.1080/10426501003773480
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Phosphorus, Sulfur, and Silicon, 185:1142–1153, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426501003773480
THERMAL REACTIONS OF β-HYDROXYSULFIDES
BEARING BENZOTHIAZOLE: SULFENIC ACID TRAPPING
VIA A SPIRO INTERMEDIATE
Nobuhiko Yamada,1 Takanori Koyasu,1 Mayumi Sonami,1
Michiko Aoi,1 Shintaro Tashiro,1 Md. Chanmiya Sheikh,1
Yusuke Ishida,1 Wataru Kawashima,1 Toshiaki Yoshimura,2
and Hiroyuki Morita1
1Department of Material Systems Engineering and Life Science, Faculty of
Engineering, University of Toyama, Japan
2Department of Environmental Applied Chemistry, Faculty of Engineering,
University of Toyama, Japan
Benzothiazolyl 2-hydroxyethyl sulfoxide (1a) was found to afford bis[2-(2-oxobenzotiazolyl)-
ethyl] disulfide (2a) in the presence of DBU at rt. 2a was formed by the condensation
of corresponding sulfenic acid intermediate. Thermolyses of 1a in the presence of ethyl
propiolate at 60–140◦C were carried out to succeed to trap sulfenic acid 6a as an intermediate.
Trapping of 2-benzothiazolyloxyenthanesulfenic acid (6a) revealed that the thermal reaction
proceeded via a five-membered spiro intermediate 5a.
Keywords Benzothiazole derivatives; β-hydroxysulfoxides; spiro intermediate; sulfenic acid;
thermal reaction
INTRODUCTION
Considerable attention has been focused on organosulfur compounds bearing hete-
rocycles, because of their interesting properties and a variety of reaction behaviors. Pre-
viously, we reported that β-phenacyl sulfoxides bearing several heteroaromatics undergo
thermolytic reactions to give the corresponding thioaldehydes or sulfines, depending on the
nature of heteroaromatics.1,2 Very recently, we reported thermolysis of β-hydroxysulfides
bearing several heteroaromatics that afforded the corresponding substituted olefins in ex-
cellent yields.
From the results of the formation of sulfur–oxygen exchange products, i.e., hydroxy
heteroaromatics, and other mechanistic studies, the olefin product was considered to be
formed via the five-membered spiro intermediates.3 In the continuing studies, we pre-
pared β-hydroxysulfoxides bearing benzothiazole and studied their thermal behavior in the
presence or absence of a base.
Received 26 December 2008; accepted 19 January 2009.
Dedicated to Professor Naomichi Furukawa on the occasion of his 70th birthday.
Address correspondence to Hiroyuki Morita, Department of Material Systems Engineering and Life Science,
Faculty of Engineering, University of Toyama, 3190 Gofuku, Toyama 930-8555, Japan. E-mail: morita@eng.u-
toyama.ac.jp
1142

SULFENIC ACID TRAPPING
1143
RESULTS AND DISCUSSION
β-Hydroxysulfoxides bearing benzothiazole were prepared by the oxidation of cor-
responding sulfides with mCPBA in good yields. First, we carried out the thermal reaction
of 1a in THF in sealed tubes. The results are summarized in Table I. The reaction pro-
ceeded slowly after 24 h to afforded bis[2-(2-oxobenzotiazolyl)-ethyl] disulfide (2a) and
2-hydrovybenzothiazole (3) in low yields, respectively. We also confirmed the control ex-
periments of the thermal reaction of 1a. Disulfide 2a was kept at 80◦C in dioxane for 24 h
to reveal that the decomposition of 2a to afford 3. In addition, in the case of 140◦C, 2a gave
the quantitative yield of 3 after 24 h. In the case of 1c–1d, which has several substituents
at the β-position, the results were different. The reactions proceeded more smoothly than
in the case of 1a, and the main product was 2-hydroxybenzothiazole, and the small amount
of corresponding olefins was also confirmed.
From these results, we presumed that the reactions proceeded via five-membered
spiro intermediate 5a by ipso-addition of hydroxy group at β-position to the 2-position of
benzothiazole. Successively, in the case of 1a, sulfenic acid 6a was formed by the ring
opening of 5a, followed by the formation of disulfides 2a4 (Scheme 1).
However, the result in entries 2–4 (Table I) seems to indicate that 3 was formed by
the elimination reaction of 5b–d as shown in Scheme 2. In these cases, the reactions of
5b–d to 3 and 7b–d are probably faster than reactions of 5b–5d to 6b–d under the high
temperature conditions.
It is known that sulfenic acids are generally unstable, and hence their isolation is
usually difficult in the cases of nonstabilization effects.5 Therefore, trapping experiments
of the sulfenic acid intermediate are quite useful and important. In order to obtain a clue for
the existence of a sulfenic acid 6a via the initially formed five-membered spiro intermediate,
we carried out the thermolysis of 1a in ethyl propiolate under several conditions. The results
are shown in Table II. The thermolyses at 60◦C and 80◦C proceeded very slowly to afford
sulfenic acid trapped product 2-(2-oxy-2-benzothiazolyl)ethyl 2-(ethoxycarbonyl)ethenyl
sulfoxide 8a in low yields, 20% and 34% after 192 h, respectively (entries 2 and 6). The
yields of target 8a increased as reaction times were prolonged (entries 3–7 and 9–11).
1
The geometry of 8a was found to be E-form by comparison of the H NMR data with
reported similar compounds having -SOCHCHCO- moiety.6 In the thermolysis at higher
Table I Thermal reactions of hydroxyuslfoxides (1a)
N
S
N
S
N
S
R
S
R
OH
+
S
+
O
Conditions
OH
2
O
1a-d
3
4a-d
2a-d
Yield (%) a
Entry
R
Conditions
2a
3
4a–d
1
2
3
4
R = H (1a)
R = H (1a)
THF, 80◦C, 24 hb
THF, 100◦C, 24 hb
CDCl3 100◦C, 4 hb
CDCl3, 100◦C, 4 hb
6
11
20
83
89
—
—
11
14
10
—
—
R = Ph (1c)
R = 2-Nap (1d)
aIsolated yields.
bIn a sealed tube.

1144
N. YAMADA ET AL.
Table II Thermal reactions of 1a in ethyl propiolate under several conditions
Yield (%)a
Entry
Conditionsb
8a
3
11
recover (1)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
60◦C, 72 h
60◦C, 192 h
80◦C, 12 h
80◦C, 24 h
80◦C, 72 h
80◦C, 192 h
100◦C, 12 h
100◦C, 24 h
100◦C, 72 h
120◦C, 5 h
120◦C, 12 h
120◦C, 24 h
140◦C, 3 h
140◦C, 5 h
140◦C, 7 h
140◦C, 12 h
12
20
12
17
23
34
25
38
59
16
44
50
33
51
44
24
5
7
6
6
7
0
0
0
0
0
0
0
0
0
trace
trace
7
10
15
17
25
61
56
72
65
54
48
64
42
0
43
10
0
52
22
6
10
8
10
24
15
24
33
trace
10
18
22
0
aIsolated yields.
bIn a sealed tube.
δ −
H
B
O
O
O
H
N
N
N
S
SH
ipso addition
S
O
S
S
S
5a
O
O
1a
N
S
SOH
O
6a
N
N
S
S
very fast
Elimination
O
S
OH
2
2a
3
Scheme 1
O
O
O
R
R
H
N
OH
Btz
S
Path A
S
SH
6b-d
SH
Btz
O
Btz O
R
ring opening
O
S
O
R
R
1b-d
O
O
S
R = Me
R = Ph
1b
1c
H
N
Path B
S
Btz OH
+
episulfoxides
formation
R = 2-Nap 1d
R
S
O
R
3
4b-d
7b-d
5b-d
Scheme 2

SULFENIC ACID TRAPPING
1145
temperature than 120◦C, starting material 1a itself revealed to be decomposed by β-
elimination. Trapping of sulfenic acid 12 was also preformed by ethyl propiolate to afford
2-benzothiazolyl 2-(ethoxycarbonyl)ethenyl sulfoxide 13 (Scheme 3). In the case at 120◦C
and 140◦C, bis[2-(ethoxycarbonyl)ethyl]ethenyl sulfoxide (10) was found to be formed in
a trace amount by trapping experiment of 2-(ethoxycarbonyl)ethenesulfenic acid 9 in the
presence of ethyl propiolate, indicating that the further β-elimination of 8a initially formed
was concurrently taking place.
O
HO
O
SH
H
N
N
S
S
N
S
S
O
S
O
O
1a
5a
6a
O
O
N
S
S
OEt
OEt
O
O
O
8a
O
N
HS
OEt
β-Elimination
OH
+
S
3
9
O
O
OEt
OEt
O
O
N
S
S
OEt
EtO
O
OEt
O
O
10
11
Scheme 3
Further, the Michael addition of 3 to ethyl propiolate also formed 2-(2-oxy-2-
benzothiazolyl) acrylic acid ethyl ester (9) slowly in a trace amount. According to the
systematic control and trapping experiments, the thermal reaction of 1a and concomitant
generation of sulfenic acids 6a, 9, and 12 revealed to proceed as is shown in Schemes 4
and 5. The same product was obtained in 64% yield in the thermal reaction of 15 in the
presence of ethyl propiolate 140◦C.
To study the reaction mechanism in detail, we also carried out the thermal reaction of
1b–d in ethyl propiolate under several conditions. The results are summarized in Table III.
In the thermal reaction of 1b, it was confirmed that sulfoxide 8b, which was formed by the
reaction of sulfenic acid 6b with ethyl propiolate, was isolated in a low yield. This result is
one of the clues to reveal the reaction mechanism of the thermal reaction. In the case of the
thermal reaction of 1b, the reaction proceeded via the formation of spiro intermediate and
then via the ring opening sulfenic acid formation (Scheme 2, Path A). 3 was also formed

1146
N. YAMADA ET AL.
O
N
SH
S
HO
O
O
N
S
N
S
β-Elimination
OEt
S
OEt
S
N
O
SOH
S
O
13
1a
12
Scheme 4
N
N
S
S
C2H5I, Et3N
N
S
m-CPBA
Et
SH
S
CH2Cl2, rt, 6 h
S
CH2Cl2, rt, 4 h
O
14
15
O
O
N
S
β-Elimination
OEt
S
OEt
15
12
°
140 C, 10 h
in a sealed tube
O
13
Scheme 5
via the elimination of 8b because the yield of 8b was not improved even under longer
reaction time (Table III, entries 1 and 2). At the higher temperature, the reaction proceeded
more quickly, and the yield of 8b was a little improved. On the other hand, in the thermal
reaction of 1c–d, the separable product was only 3 and other expected compounds 7c–d
or corresponding olefin 4c–d were not confirmed to give inseparable complicated mixture
(entries 5 and 6). It is likely that the reaction proceeded via mainly Path B or via both Paths
A and B. 4c has a benzyl proton, and the direct episulfoxide formation proceeded more
Table III Reactions of hydroxysulfoxides (1) under several conditions
N
S
N
S
N
S
S
Base
+
OH
S
O
Conditions
OH
2
O
1a
2a
3
Yield (%)a
Entry
Conditions
THF, rt, 3.0 h
THF, rt, 10 min.
THF, rt, 1 h
Base
2a
3
1
2
3
4
5
6
7
tert-BuOK (1.0 equiv.)
DBU (1.0 equiv.)
DBU (1.0 equiv.)
DBN (1.0 equiv.)
DABCO (2.0 equiv.)
DMAP (2.0 equiv.)
Et3N (2.0 equiv.)
34
84
55
36
14
3
30
trace
36
30
8
THF, rt, 2 h
THF, 65◦C, 4.0b
THF, 65◦C, 4.0b
THF, 65◦C, 4.0b
3
0
0
aIsolated yields.
bIn a sealed tube.

SULFENIC ACID TRAPPING
1147
Table IV The reaction of hydroxysulfoxides having several substituents at β-positon under various conditions
Yield (%)b
Entry
R
Conditions
3
8b–d
1
2
3
4
5
6
7
8
9
Me (1b)
Me (1b)
Me (1b)
Me (1b)
Ph (1c)
Ph (1c)
Me (1b)
Ph (1c)
ethyl propiolate, 100◦C, 12 ha
ethyl propiolate, 100◦C, 24 ha
ethyl propiolate, 120◦C, 12 ha
ethyl propiolate, 140◦C, 5.0 ha
ethyl propiolate, 80◦C, 12 ha
ethyl propiolate, 100◦C, 12 ha
DBU (1.0 equiv.), THF, rt, 1.0 h
t-BuOK (1.0 equiv.), THF, rt, 1.0 h
DBU (1.0 equiv.), THF, rt, 1.0 h
11
40
57
43
89
90
50
85
70
9
9
17
34
0
0
10
—
—
2-Nap (Id)
aIn a sealed tube.
bIsolated yields.
easily than 4a and 4b. If the reaction proceeded via path A, elimination of BtzO group is
easier because of the benzyl proton of 5c or 5cꢀ. These are the reasons why the sulfenic
acids 6c or 6cꢀ were not trapped with ethyl propiolate.
The thermolysis in the presence of bases is also very interesting, since all the reaction
steps, for example, in Table IV 1a–d to 6a–d, are considered to be catalyzed by bases.
Therefore, we carried out the reactions of 1a–d with several bases. Expectedly, the reaction
of 1a with bases proceed smoothly even at room temperature to afford disulfide 2a in a
good yield. The best results were obtained in the case of DBU. The starting material 1a
was consumed within 10 min to afford 2a in 84% yield. It was confirmed that the control
reaction of 1a with bases for a long time afforded 2-hydroxybenzothiazole in a higher yield.
However, when weaker bases DABCO and DMAP were used, the reaction proceeded very
slowly, and the staring material was recovered in good yields even at higher temperature.
In addition, the reaction of 1a did not proceed at all in the presence of triethylamine.
In the thermal reaction of 1b, it was confirmed that sulfoxide 8b, which was formed
by the reaction of sulfenic acid 5b or 5d with ethyl propiolate, was isolated in a low yields.
This result is one of the clues to reveal the reaction mechanism of the thermal reaction. In
the case of the thermal reactions of 1a and 1b, the reaction proceeded via the formation
of spiro intermediate and then via sulfenic acid formation (Path A) as shown in Scheme
4. 3 was also formed via the elimination of 8b, because the yield of 6b was not improved
even under longer reaction times (Table IV, entries 1 and 2). At the higher temperature, the
reaction proceeded faster, and the yield of 8b was a little improved. On the other hand, the
results of thermal reaction of 1c were unexpected. The separable product was only 3, and
other expected compounds 7c or corresponding olefin stylene were not identified to give
inseparable complicated mixture (entries 5 and 6). It is likely that the reaction proceeded
via Path B or via both Paths A and B. 4c has a benzyl proton, and the direct episulfoxide
formation proceeded more easily than 4a and 4b. If the reaction proceeded via path A,
elimination of the BtzO group is easier because of benzyl proton of 5c or 5cꢀ. These are
the reasons why the sulfenic acid 5c or 5cꢀ were not trapped with ethyl propiolate. The
reactions under milder conditions were carried out with several bases at room temperature.
The reaction of 1b, 1c, and 1d with 1.0 equiv. of DBU or tBuOK proceeded smoothly to
afford 3 as only separable product in good yields. In addition, in the case of 1b, the trace

1148
N. YAMADA ET AL.
amount of corresponding disulfide 2b was obtained. However, corresponding episulfoxides
7b–d and disulfides 2c–d were not isolated at all. As the result, the possible reaction
mechanism of thermal reaction seems to be path A in the case of 1a and 1b, and path A
and/or path B in the cases of 1c and 1d.
The thermal reactions of hydroxysulfides were also studied as our associated work.
The β-hydroxysulfones were prepared by the oxidation of corresponding β-hydroxysulfides
with mCPBA. The thermolysis of 2-benzothiazolyl 2-hydroxyphenetyl sulfone (16a) at
140◦C was carried out in CDCl3. The reaction mixture was directly measured by 1H NMR
to reveal the formation of 3 and corresponding 4c in quantitative yield, respectively. The
thermolysis of β-hydroxysulfone having substituents at α- and β-position were also used
to study 16b, and the same product 3 and corresponding olefin 4e were also obtained
quantitatively with the formation of other products. Stilbene (4e) was obtained as only
1
trans-isomer, which was compared with H NMR of authentic trans-stilbene and cis-
stilbene (Scheme 6).
The plausible formation pathway of 3 and 4 is illustrated in Scheme 7. β-
Hydroxysulfide (1a) leads to spiro intermediate 17a by the internal ipso-addition of the
hydroxy group at β-position. The possible decomposition route of this intermediate to 3
and 4a will be the concerted ring-opening route, followed by the elimination of 18a to
form 3 and 4a. In this case, the good leaving ability of hydroxy benzothiazole group seems
to operate the crucial role. The results also show the clue of the mechanism of modified
Julia olefination. The isolation of olefins is also easy by using silica gel flash column;
therefore these thermal reactions are expected to be useful in olefin synthesis.
O
OH
N
S
N
S
R1
S
OH
R2
R1
+
°
CDCl3, 140 C, 4 h
O
R2
in a sealed tube
quantitative yields
4c, 4e
16a (R1 = Ph, R2 = H)
16b (R1 = Ph, R2 = Ph)
3
Scheme 6
O
H
HO
Ph
H O
N
S
Ph
O
N
S
N
S
ipso-addition
S
O
Ph
O
S
S
O
O O
16a
17a
18a
N
- SO2
OH
+
Ph
4c, 4e
Scheme 7 Probable mechanism of thermolysis of β-hydroxysulfide 16a.
S
3
In conclusion, we found the reactions 1 in the presence of bases (DBU and tert-
butoxide) proceeded via five-membered spiro intermediate 4, and resulted in the formation

SULFENIC ACID TRAPPING
1149
of sulfenic acid 5. The key compound 5 was successfully trapped with ethyl propio-
late. We expect that the thermal reaction of β-hydroxysulfoxides and the reaction of β-
hydroxysulfoxides with DBU are simple sulfenic acid preparation procedures in the field of
organic synthesis. Thermal reactions of β-hydroxysulfones are useful in olefin synthesis,
and in addition, further purification of olefins is very easy by simple silica flash column
chromatography. Additionally, this methodology does not require any strong acid, unstable
toxic metallic reagents, or other expensive reagents.
EXPERIMENTAL
All the melting points were uncorrected using micro melting point apparatus. 1H NMR
(400 MHz) and 13C NMR (100 MHz) spectra were recorded in CDCl3 using TMS as an
internal standard. The elemental analyses were performed at the Microanalytical Laboratory
of the Department of Material Systems Engineering and Life Science, University of Toyama.
All the reactions were monitored with TLC, and the products were separated by column
chromatography using silica gel 60 and also by preparative layer chromatography using
silica gel 60 PF254 with UV detection. All the reagents were of the highest quality and were
further purified by distillation or recrystallization. The solvents were further purified by
general method.
General Procedure for the Preparation of β-Hydroxysulfoxides 1a–d
To a solution of β-hydroxysulfides (3.00 mmol) in distilled dichloromethane (30 mL),
a solution of m-chloroperbenzoic acid in dichloromethane was added slowly with stirring at
0◦C under N2. After the addition, the reaction mixture was stirred at room temperature. After
the starting materials were consumed, the mixture was washed with saturated NaHCO3 aq
four times. The organic layer was dried over anhydrous MgSO4. Then the solvent was
removed to afford crude β-hydroxysulfoxides 1a–d, which were purified by silica flash
column chromatography and recrystallization.
2-Benzothiazolyl 2-hydroxyethyl sulfoxide (1a). Yield 70% (white solid from
dichloromethane-hexane-hexane); mp 110–112◦C; 1H NMR (CDCl3): δ 8.06–8.08 (m, 1H),
8.01–8.03 (m, 1H), 7.56–7.66 (m, 1H), 7.49–7.53 (m, 1H), 4.24–4.30 (m, 1H), 4.14–4.20
(m, 1H), 3.60–3.66 (m, 1H), 3.37–3.43 (m, 1H), 2.60 (br, 1H),; 13C NMR (CDCl3): δ 176.9,
153.8, 136.0, 127.1, 126.3, 124.0, 122.3, 57.8, 56.; IR (KBr): ν = 3408, 3086, 3060, 2920,
1476, 1426, 1387, 1311, 1134, 1048, 990, 766 cm−1; Anal. Calcd. For C9H9NO2S2: C,
47.56; H, 3.9; N, 6.16. Found. C, 47.54; H, 4.05; N, 6.20.
2-Benzothiazolyl 2-hydroxypropyl sulfoxide (1b). Inseparable mixture of di-
astereomers (the ration of major:minor isomer was 1.4:1); yield 65%; mp 81–83◦C (white
1
solid from CH2Cl2, diethyl ether and hexane); H NMR (CDCl3, 400 MHz) δ 8.06–8.09
(m, 2H), 8.00–8.04 (m, 2H), 7.56–7.61 (m, 2H), 7.49–7.54 (m, 2H), 4.58–4.66 (m, 1H),
4.45–4.53 (m, 1H), 3.49 (dd, J = 13.6, 10.0 Hz, 1H), 3.35–3.44 (m, 2H), 3.23 (dd, J = 2.0,
13.6 Hz, 1H), 1.40 (d, J = 6.4 Hz, 1H), 1.31 (d, J = 6.4 Hz, 1H), 13C NMR (CDCl3):δ
177.3, 176.8, 153.9, 153.7, 136.1, 135.9, 127.03 (2C), 126.30, 126.26, 123.94 (2C), 122.28,
122.26, 63.8, 63.7, 63.3, 62.4, 23.3, 23.3; IR (KBr): ν = 3365, 1455, 1424, 1073, 1060,
1021; Anal. Calcd. For C9H9NO2S2: C, 49.77; H, 4.59; N, 5.80. Found. C, 49.80; H, 4.92;
N, 5,82.
2-Benzothiazolyl 2−hydroxyphenethyl sulfoxide (1c). An inseparable mix-
ture of diastereomers (the ration of major:minor isomer was 2.6:1.0); yield 72%; mp
1
146–160◦C (dec.) (white soft solid from CH2Cl2, diethyl ether and hexane); H NMR

1150
N. YAMADA ET AL.
(CDCl3): δ 8.03–8.07 (m, 2H), 7.98–8.02 (m, 2H), 7.54–7.59 (m, 2H), 7.47–7.53 (m,
2H), 7.24–7.42 (m, 10H), 5.49–5.52 (m, 1H), 5.37–5.39 (m, 1H), 3.86 (d, J = 3.2 Hz,
2H), 3.63–3.70 (m, 2H), 3.56 (dd, J = 13.2, 3.2 Hz, 1H), 3.41 (dd, J = 13.2, 3.2 Hz,
1H),13C NMR (CDCl3, major isomer): δ 176.7, 153.9, 141.4, 136.0, 128.7, 128.3, 127.1,
126.3, 125.7, 124.0, 122.3, 68.9, 63.2; IR (KBr): ν = 3374, 1052 cm−1; Anal. Calcd. For
C9H9NO2S2: C, 59.38; H, 4.32; N, 4.62. Found. C, 59.19; H, 4.73; N, 4.60.
2-Benzothiazolyl 2-(2-naphthyl)-2-hydroxyethyl sulfoxide (1d). Insepara-
ble mixture of diastereomers (the ration of major:minor isomer was 1.7:1.0); Yield 77%;
mp 115–116◦C (white solid from CH2Cl2, diethyl ether and hexane); 1H NMR (CDCl3): δ
8.02–8.07 (m, 2H), 7.95–8.00(m, 2H), 7.77–7.89 (m, 8H), 7.41–7.58 (m, 10H), 5.66 (dd,
J = 9.2, 3.6 Hz, 1H), 5.54 (dd, J = 9.6, 2.0 Hz, 1H), 3.74 (dd, 13.6, 10.0 Hz, 2H), 3.65 (dd,
J = 13.6, 3.6 Hz, 1H), 3.49 (dd, J = 9.6, 2.0 Hz, 1H), 3.63–3.70 (m, 2H), 3.56 (dd, J =
13.2, 3.2 Hz, 1H), 3.41 (dd, J = 13.2, 3.2 Hz, 1H),13C NMR (CDCl3): δ 177.1, 176.6, 153.9,
153.7, 138.72, 138.67, 136.0, 135.97, 133.19 (2C), 133.16, 133.11, 128.7, 128.6, 128.03,
128.00, 127.6, 127.65, 127.1, 127.0, 126.39, 126.37, 126.30, 126.29, 126.26, 126.21, 124.9,
124.7, 123.97, 123.95, 123.44, 123.37, 126.3 (2C), 69.4, 69.0, 63.6, 63.1, IR (KBr): ν =
3374, 1052 cm−1; Anal. Calcd. For C9H9NO2S2: C, 64.56; H, 4.28; N, 3.96. Found. C,
64.56; H, 4.13; N, 4.05
Bus [2-(2-oxy-2-benzothiazolyl) ethyl] disulfide (2a). Mp 112–114◦C (white
1
solid from dichloromethane-diethyl ether-hexane); H NMR (CDCl3): δ. 3.20 (t, J = 6.8
Hz, 2H), 4.84 (t, J = 6.4 Hz, 2H), 7.20–7.26 (m, 1H), 7.33–7.37 (m, 1H) 7.61–7.68 (m,
2H); 13C NMR (CDCl3): δ. 37.26, 69.28, 120.89, 121.28, 123.62, 126.00, 131.97, 149.14,
172.28; IR (KBr): ν = 2958, 1550, 1540, 1443, 1243, 1212, 1073, 1017, 954, 758 cm−1
;
MS (EI): m/z 421.0 (M+1); Anal. Calcd. For C18H16N2O2S4: C, 51.40; H, 3.83; N, 6.66.
Found. C, 51.25; H, 3.83; N, 6.66.
2-Hydroxybenzothiazole (3). 7 1H NMR (CDCl3): δ 9.56 (br, 1H), 7.41 (d, 8.0 Hz,
1H), 7.26–7.30 (m, 2H), 7.14–7.18 (m, 2H); 13C NMR (CDCl3): δ 172.85, 135.28, 126.50,
123.90, 123.26, 123.26, 122.55, 111.68.
2-(2-Oxy-2-benzothiazolyl)ethyl 2-(ethoxycarbonyl)ethenyl sulfoxide
(8a). Mp 82–84◦C (pale yellow solid from dichloromethane-diethyl ether-hexane);
1H-NMR (CDCl3): δ 7.69 (d, J = 6.8 Hz, 1H), 7.65 (d, J = 8.4 Hz, 1H), 7.38 (t, J = 7.2
Hz, 2H), 7.25 (t, J = 7.6 Hz, 2H), 6.70 (d, J = 14.8 Hz, 1H), 5.04–5.10 (m, 1H), 4,92–4.99
(m, 1H), 4.24 (q, J = 7.6 Hz, 2H), 3.45–3.51 (m, 1H), 3.21–3.27 (m, 1H), 31 (t, J = 3.2
Hz, 3H); 13C-NMR (CDCl3): δ 171.56, 163.50, 148.89, 132.05, 126.79, 126.15, 126.14,
123.90, 121.34, 121.07, 62.96, 61.42, 51.83, 14.07; IR (KBr): ν = 3018, 2926, 1711, 1535,
1445, 1370, 1298, 1249, 1217, 1158, 1042, 754 cm−1; Anal. Calcd. For C14H15NO4S2: C,
51,67; H, 4.65; N, 4.30%. Found. C, 51.57; H, 4.66; N, 4.32%.
2-(2-Oxy-2-benzothiazolyl)ethyl 2-(ethoxycarbonyl)ethenyl sulfoxide
1
(8b). Clear yellow oil (unstable compound), H-NMR (CDCl3): δ 7.62–7.77 (m, 3H),
7.34 (t, J = 7.6 Hz, 1H), 7.24 (t, J = 7.6 Hz, 1H), 7.71 (d, J = 15.6 Hz, 1H), 5.76–5.84
(m, 1H), 4.26 (q, J = 7.2 Hz, 2H), 3,38 (dd, J = 13.2, 7.2 Hz, 1H), 3.04 (dd, J = 13.2,
4.0 Hz, 1H), 1.67 (d, J = 6.4 Hz, 3H), 1.32 (t, J = 7,2 Hz, 3H), HRMS (EI) Calcd for
C15H17NO4S2 339.0599, found m/z 339.0590 (M+)
Bis[2-(ethoxycarbonyl)ethyl]ethenyl sulfoxide (10). Clear yellow oil;1 H
NMR (CDCl3): δ 7.54 (d, J = 15.2 Hz, 1H), 6.64 (d, J = 14.8 Hz, 1H), 4.26 (q, J =
7.2 Hz, 3H), 1.32 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3): δ 163.41, 146.35, 126.08, 61.6,
14.1; IR (NaCl): ν = 1723, 1293, 1265, 1219, 1084, 1031 cm−1; HRMS (EI) Calcd for
C10H14O5S 246,0562, found m/z 246.0562.

SULFENIC ACID TRAPPING
1151
2-(2-Oxy-2-benzothiazolyl) acrylic acid ethyl ester (11). Mp 51–53◦C (white
1
solid from dichloromethane-hexane); H NMR (CDCl3): δ 7.93 (d, J = 14.4 Hz, 1H),
7.44–7.46 (m, 1H), 7.35–7.39 (m, 2H), 7.25–7.29 (m, 1H), 6.92 (d, J = 14.4 Hz, 1H), 4.29
(q, J = 7.2 Hz, 2H), 1.34 (t, J = 7.2 Hz, 3H); 13C NMR (CDCl3): δ 168.88, 167.20, 134.92,
133.59, 126.90, 124.82, 122.95, 122.06, 111.55, 110.48, 60.79, 14.28; IR (KBr) ν = 1712,
1700, 1634, 1471, 1272, 1150 cm−1; HRMS (EI) Calcd for C12H11NO3S 249.0460, found
m/z 294.0463 (M+).
2-Benzothiazolyl 2-(ethoxycarbonyl)ethyl sulfoxide (11). Clear pale yellow
oil; 1H NMR (CDCl3): δ 8.10 (d, J = 7.6 Hz, 1H), 7.99 (d, J = 7.6 Hz, 1H), 7.80 (d, J =
15.6 Hz, 1H), 7.57 (t, J = 7.6 Hz, 1H), 7.51 (t, J = 7.6 Hz, 1H), 6.83 (d, J = 15.6 Hz, 1H),
4.23 (q, J = 7.2 Hz, 3H), 1.30 (t, J = 7.2 Hz, 2H); 13C NMR (CDCl3, 100 MHz) δ 173.8,
163.2, 153.5, 148.5, 135.7, 127.1, 126.6, 126.3, 124.2, 122.3, 61.6, 14.0; HRMS (EI) Calcd
for C12H11NO3S2 281.0180, found m/z 281.0198 (M+).
Reactions of 2-Benzothiazolyl 2-Hydroxyethyl Sulfoxide (1a)
with Several Bases at Room Temperature
To a solution of 2-benzothiazolyl 2-hydroxyethyl sulfoxide (1a) (50.0 mg, 0.220
mmol) in anhydrous THF, a solution of several bases dissolved into THF was added
with stirring at room temperature under nitrogen. The reaction was monitored by TLC.
After the reaction, the mixture was washed with ethyl acetate, and saturated ammonium
hydrochloride solution removed the bases. Each product was isolated with general methods.
Reactions of 2-Benzothiazolyl 2-Hydroxyethyl Sulfoxide (1)
with Several Bases at 65◦C in a Sealed Tube
To a 2 mL Pyrex tube, 2-benzothiazolyl 2-hydroxyethyl sulfoxide (1) (50 mg, 0.220
mmol) and several bases (0.440mmol) were added, and this tube was sealed after the
replacement with N2. After the reaction, the mixture was washed with ethyl acetate, and
saturated ammonium hydrochloride solution removed the bases. Each product was isolated
with silica flash column using hexane:AcOEt (2:1).
Thermal Reactions of 2-Benzothiazolyl 2-Hydroxyethyl Sulfoxide (1)
in Ethyl Propiolate
To a 2 mL Pyrex tube, 2-benzothiazolyl 2-hydroxyethyl sulfoxide (1) (50 mg, 0.220
mmol) and ethyl propiolate (250 µL, 2.47 mmol) were added, and this tube was sealed
after the replacement with N2. After the reaction, excess ethyl propiolate was evaporated
off in vacuo, and the residue was purified by silica short flash column. Each product was
isolated by PTLC using hexane:AcOEt (3:1).
Thermal Reaction of 2-Hydroxybenzothiazole (3) with Ethyl Propiolate
A mixture of 2-hydroxybenzothiazole (50.6 mg, 0.335 mmol) and ethyl propiolate
(500 µL, 2.94 mmol) was warmed in a Pyrex tube, and then this tube was sealed under
nitrogen atmosphere. Heating at 140◦C for 6 h afforded 2-(2-oxy-2-benzothiazolyl) acrylic
acid ethyl ester (9) (27.4 mg, 0.110 mmol) in 33% yield.

1152
N. YAMADA ET AL.
Thermal Reaction of Bis[2-(2-oxy-2-benzothiazolyl)ethyl] Disulfide (2)
A solution of 2 (60.0 mg, 0.143 mmol) in 1.0 mL anhydrous 1,4-dioxane was warmed
to 140◦C in a sealed tube. After 24 h, the solvent was evaporated off, and the product was
purified by silica flash column using dichloromethane to afford 3 in 82% yield.
2-Benzothiazolyl Ethyl Sulfide (14)8
To a mixture of 2-mercaptobenzothiazole (1.10 g, 6.59 mmol) and ethyl iodide
(630 µL, 7.91 mmol) in distilled dichloromethane (30 mL), anhydrous triethylamine (3.0
mL) was added with stirring at room temperature. After the starting materials were con-
sumed, the solvent and excess triethylamine were evaporated off in vacuo. The residue was
washed with dichloromethane (20 mL) and pure water (20 mL × 3), and the organic layer
was dried over anhydrous magnesium sulfate. After removal of the solvent, the residue
was purified by silica short flash column using dichloromethane:hexane (1:1) to afford
2-benzothiazolyl ethyl sulfide in a quantitative yield.
1H NMR (CDCl3, 400MHz) δ 7.87 (d, J = 8.4 Hz, 1H), 7.76 (d, J = 8.4 Hz, 1H),
7.39–7.43 (m, 1H), 7.27–7.31 (m, 1H), 3.36 (q, J = 7.2 Hz, 2H), 1.50 (t, J = 7.2 Hz, 3H);
HRMS (EI) Calcd for C9H9NS2 195.0176, found m/z 195.0176 (M+).
2-Benzothiazolyl Ethyl Sulfoxide (15)
To a solution of 2-benzothiazolyl ethyl sulfide (473 mg, 2.42 mmol) in distilled
dichloromethane (20 mL), a dichloromethane solution of m-chloroperbenzoic acid (70%)
(597 mg, 2.42 mmol) was added with stirring at room temperature under nitrogen. The
reaction was monitored by TLC. After 4 h, the starting material was consumed smoothly.
The reaction mixture was washed with 5% aqueous potassium carbonate solution (20 mL ×
5) to remove formed m-chlorobenzoic acid. The organic phase was dried over anhydrous
magnesium sulfate. After removal of the solvent, 2-benzothiazolyl ethyl sulfoxide was ob-
tained. Yield 81%; mp 41–43◦C (white solid from dichloromethane-diethylether-hexane);
1H NMR (CDCl3): δ 8.07 (d, J = 8.0 Hz, 1H), 8.01 (d, J = 8.0 Hz, 1H), 7.57 (dd, J =
8.0, 1.2 Hz, 1H), 7.50 (dd, J = 8.0, 1.2 Hz, 1H), 3.16–3.25 (m, 1H), 3.29–3.38 (m, 1H),
1.36 (t, J = 7.6 Hz, 1H); 13C NMR (CDCl3): δ 177.2, 166.7, 153.4, 126.1, 123.9, 122.4,
50.1, 5.5; IR (KBr): ν = 3062, 2973, 2957, 1472, 1062, 1025, 766 cm−1; Anal. Calcd. For
C9H9NOS2: C, 51.16; H, 4.29; N, 6.63. Found. C, 51.14; H, 4.28; N, 6.69.
Thermal Reaction of 2-Benzothiazolyl Ethyl Sulfoxide
in Ethyl Propiolate
To a 2 mL Pyrex tube, 2-benzothiazolyl ethyl sulfoxide (1) (50.0 mg, 0.237 mmol)
and ethyl propiolate (250 µL, 2.47 mmol) were added, and this tube was sealed after the
replacement with N2. After the reaction, excess ethyl propiolate was evaporated off in
vacuo, and 2-benzothiazolyl 2-(ethoxycarbonyl)ethyl sulfoxide (13) was isolated by PTLC
using hexane:AcOEt (3:1) as a clear yellow oil (42.6 mg, 64%).

SULFENIC ACID TRAPPING
1153
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