Thermolysis of β-hydroxysulfides bearing several heteroaromatics

Article abstract of DOI:10.1016/j.tet.2007.01.043

Thermolyses of β-hydroxysulfides 2, bearing groups, such as 2-benzothiazolyl and 4-(4-methyl)-4H-1,2,4-triazolyl groups, were studied and found to afford the corresponding substituted styrenes 5 and hydroxy heteroaromatics in good yields, respectively. The product distribution change in the course of the thermolysis of 2a was also studied. The olefin products 5a were considered to be formed by the thermal desulfurization of the corresponding thiiranes 4a initially formed via the five-membered spiro intermediate 6a.

Full text of DOI:10.1016/j.tet.2007.01.043

Tetrahedron 63 (2007) 3408–3414
Thermolysis of b-hydroxysulfides bearing several heteroaromatics
*
Nobuhiko Yamada, Masayoshi Mizuochi and Hiroyuki Morita
Department of Material Systems Engineering and Life Science, Faculty of Engineering, University of Toyama,
3190 Gofuku, Toyama 930-8555, Japan
Received 27 November 2006; revised 22 January 2007; accepted 23 January 2007
Available online 25 January 2007
Abstract—Thermolyses of b-hydroxysulfides 2, bearing groups, such as 2-benzothiazolyl and 4-(4-methyl)-4H-1,2,4-triazolyl groups, were
studied and found to afford the corresponding substituted styrenes 5 and hydroxy heteroaromatics in good yields, respectively. The product
distribution change in the course of the thermolysis of 2a was also studied. The olefin products 5a were considered to be formed by the thermal
desulfurization of the corresponding thiiranes 4a initially formed via the five-membered spiro intermediate 6a.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
1a–h were prepared easily by reactions of a-haloketones
with heterocyclic thiols in the presence of triethylamine in
CH2Cl2 at rt. The heterocyclic sulfides containing tertiary
hydroxy group 2i were prepared by the Grignard reaction
with corresponding b-ketosulfides.11
Recently, we have reported that the thermolytic reaction of
phenacyl sulfoxides bearing several heteroaromatics, such
as 2-N-oxypyridyl, 2-benzothiazolyl, 5-(1-methyl)-1,2,3,4-
tetrazolyl, and 5-(1-phenyl)-1,2,3,4-tetrazolyl groups
afforded the corresponding thioaldehyde1,2 or sulfines,3 de-
pending on the substituted heteroaryl groups. Thioaldehydes
were considered to be formed by the elimination of hydroxy
heteroaromatics via the sulfenate ester intermediate gener-
ated by rearrangement of the starting sulfoxide. In contrast to
the other substituents, 5-(1-phenyl)-1,2,3,4-tetrazolyl deriv-
atives revealed to afford sulfines via the elimination of tetr-
azole by the E2 type elimination mechanisms. In a continuing
study of the thermolysis of b-ketosulfoxides in order to shed
further light intotheir diverse field of synthetic organic chem-
istry4–6 and also potent pharmaceutical derivatives,7–9 we
havepreparedseveralheteroarylsubstitutedb-hydroxysulfide
derivatives and studied their thermolysis behaviors.
First, the thermolysis of 2a without solvent was studied at
several temperatures. The reaction proceeded smoothly
with increasing the temperature above 150 ꢀC to afford 2-
hydroxybenzothiazole (3) in a quantitative yield. At 160 ꢀC,
formation of styrene (5a) became maximum and then, at
higher temperature decreases gradually, probably due to
the thermal polymerization of 5a at higher temperature.
The results are summarized in Table 1 and illustrated in
Figure 1.
Next, thermolysis of 2-benzothiazolyl 2-hydroxy-2-(2-naph-
thyl)ethyl sulfide (2c) in p-xylene was found to afford 3 and
2-vinylnaphthalene (5c) in a quantitative and 82% yield,
respectively.
Herein, we report the synthesis of b-hydroxysulfides bearing
several heteroaromatics and their thermal behavior in mech-
anistic viewpoints. Their applications for several olefin syn-
theses are also described.
Table 1. Thermolysis of 2-benzothiazolyl 2-hydroxyphenethyl sulfide (2a)
under neat conditions
OH
N
S
N
S
Δ
S
+
OH
30 min
2. Results and discussion
in sealed tubes
2a
3
5a
2.1. Thermolysis of 2-benzothiazolyl 2-hydroxy-
phenethyl sulfide (2a)
Entry
Temperature (ꢀC)
Yield (%)a
3
5a
Recovery
Among many synthetic methods for b-hydroxysulfides,10 we
have used the reduction of b-ketosulfides. b-Ketosulfides
1
2
3
4
5
6
130
140
150
160
170
180
8
23
66
98
100
100
5
14
39
44
30
16
92
77
34
4
0
0
Keywords: b-Hydroxysulfides; Benzothiazole; Thermolysis; Spiro com-
pounds; Olefin syntheses.
* Corresponding author. Tel.: +81 76 445 6851; fax: +81 76 445 6703;
e-mail: morita@eng.u-toyama.ac.jp
Determined by 1H NMR.
a
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.01.043

N. Yamada et al. / Tetrahedron 63 (2007) 3408–3414
3409
100
80
60
40
20
0
100
2a
3
5a
80
60
40
20
2a
3
4a
5a
120
130
140
150
160
170
180
temperature (°C)
0
0
1
2
3
4
5
Figure 1. Thermolysis of 2-benzothiazolyl 2-hydroxyphenethyl sulfide
(2a).
time (h)
Figure 2. Time dependence study of thermolysis of 2a.
TLC monitoring in the progress of thermolysis of 2c in
p-xylene revealed the initial formation of the compound
other than 3 and 5c. In order to identify the intermediate
product, the thermal reaction of 2a in the presence of mesi-
tylene as an internal standard was carried out every 30 min
interval for 5.0 h at 140 ꢀC in CDCl3 in sealed tubes. The
product identification and distribution measurements were
directly carried out by 1H NMR. The intermediate was
revealed to be phenyl episulfide 4a by comparison with an
authentic sample prepared by the known method.12 The
results are summarized in Table 2.
Table 3. Thermolysis of b-hydroxysulfides bearing several heteroaromaticsa
OH
Ar OH +
5c
Ar
S
CDCl3
140 °C, 5 h
2-Nap
2c, 2f-h
Entry
Ar
Yield (%)b
Ar–OH
92
5c
Recovery
0
N
S
2c
1
2
86
90
Me
The time dependence study revealed that the maximum yield
of 3 approximately reached at around 1.5 h as illustrated in
Figure 2. Consequently, the olefin 5a was obviously formed
by the desulfurization of 3 initially formed.
N
95
0
2f
N
N
Ph
N
3
0
0
0
0
97
82
N
N
2g
N
2.2. Thermolysis of b-hydroxysulfides bearing several
heteroaromatics
N
4
2h
We have extended the thermolysis of b-hydroxysulfides
bearing heteroaromatics other than benzothiazole. The
results are summarized in Table 3. In the case of 2c and
2f (entries 1 and 2), thermolysis proceeded smoothly
to afford the corresponding hydroxy heteroaromatics and
a
In sealed tubes.
Determined by 1H NMR.
b
2-vinylnaphthalene (5c) in excellent yields. However, in
the case of b-hydroxysulfides bearing 5-(1-phenyl)-1,2,3,4-
tetrazolyl group 2g and 2-pyridyl group 2h, the reaction
did not proceed and starting materials were recovered quan-
titatively. Probably, in these cases the formation of spiro in-
termediates will be retarded greatly by both sterically and
electronically.
a
Table 2. Thermal reaction of 2a in CDCl3
S
Ph
Ph
3
2a
+
+
140 °C
CDCl3,
Time (h)
4a
5a
Entry
Yield (%)b
2.3. Reaction mechanism of thermolysis of hydroxy-
sulfides
3
4a
5a
Recovery
1
2
3
4
5
6
7
8
9
0.0
0.5
1.0
1.5
2.0
2.5
3.0
4.0
5.0
0
21
36
49
68
74
75
83
82
0
3
0
3
100
75
63
48
38
30
17
0
Almost quantitative formation of 2-hydroxybenzothiazole
3 suggested that the thermolyses of b-hydroxysulfides
apparently involve oxygen–sulfur exchange. The plausible
formation pathway of 3 and 5 is illustrated in Scheme 1.
b-Hydroxysulfide (2a) leads to spiro intermediate 6a by
the internal ipso-addition of the hydroxy group at b-position.
The possible decomposition route of this intermediate to 3
and 4a will be either Path A or Path B, or both. Path A
is the route for the thiirane 4a formation, and Path B is the
21
22
14
13
10
0
10
21
33
42
52
61
65
0
0
a
In sealed tubes.
Determined by 1H NMR.
b

3410
N. Yamada et al. / Tetrahedron 63 (2007) 3408–3414
H
N
S
Path A
S
OH
+
Ph
Ph
O
S
N
episulfide formation
Ph
HO
S
Ph
4a
3
S
H
N
N
S
HS
O
O
S
Path B
N
S
2a
Ph
ring opening
S
6a
7a
- S
thermal
desulfurization
S
Ph
Ph
4a
5a
Scheme 1. Probable mechanism of thermolysis of b-hydroxysulfide 2a.
concerted ring-opening route, followed by the elimination of
7a to form 4a. In both cases, the good leaving ability of
hydroxybenzothiazole group seems to operate the crucial
role. The final product, olefin 5a was formed by the thermal
desulfurization from 4a.
completely. In these cases, probably the step 2a to 6a would
be accelerated by the increase of nucleophilic addition of
hydroxy group to NC double bond. Therefore, the reason
why the reaction was retarded contrary to the expectation
would be due to the following steps, i.e., ipso-ring opening
and/or episulfide formation steps. However, the more plausi-
ble reason is not clear at present.
In order to obtain a clue to clarify the mechanism, trapping
experiment of thiol 7a in the presence of ethyl propiolate or
N-phenylmaleimide was carried out. However, the resultant
Michael addition product was not obtained. Further, deute-
rium labeled compound 2c0, which was prepared by the re-
duction of 1b with NaBD4, demonstrated the thermolysis
under the same conditions to reveal the formation of 5c0
with no loss of deuterium content (Scheme 2). These results
also suggest the pathway via the spiro intermediate 7a
among other possible routes to olefin 5 in thermolysis of 2a.
The reaction of 2a in the presence of stronger bases in protic
solvent, such as potassium tert-butoxide or sodium meth-
oxide, revealed that the reaction proceed rapidly to form 3
and 5a. The discrepancy between amine base and alkoxide
bases may be accounted for by the strong coordination be-
tween metal cation and the nitrogen anion, and probably by
the participation of b-sulfur atoms, resulted in the formation
of 2a-3 predominately as depicted in Scheme 3. Further, in
the case of alkoxide base, the formation of thiolate anion of
7a0 will be the driving force to accelerate the reaction, Path
B in Scheme 1, to produce 3 and 4a by internal SN
reaction. Similar results have been reported in the reaction
of thiazole derivatives in the presence of sodium methoxide13
and oxazoline derivatives in the presence of butyllithium.14
D
N
D
D
N
S
R
+
+
OD
S
R
140 °C, 2 h
R
S
S
3'
DO
4c'
5c'
2c' (R = 2-Nap)
D content = Ca. 99%
Scheme 2. Thermolysis of deuterium introduced b-hydroxysulfide 2c0.
Additionally, in view of the retardation effect of amine, ther-
molysis was suggested to proceed by the homolytic pro-
cesses. The thermolysis of 2a in the presence of radical
scavenger (2,6-di-tert-butylphenol) or initiator (2,20-azo-
bis(2-methylpropionitrile)) was carried out, however, the
reaction acceleration or retardation was not observed. There-
fore, the involvement of homolytic process will be excluded.
All these results seem to suggest that the thermal reaction
proceed via intramolecular addition of hydroxy group at
b-position to NC double bond forming spiro intermediate
6a, probably via Path A and successively via the concerted
episulfide formation in Scheme 1.
The thermolysis in the presence of bases is also interesting,
since all the reaction steps in Scheme 1, i.e., those of 2a to
6a and Path A or Path B, are considered to be catalyzed by
base. Therefore, the thermolysis of 2a and 2b in the presence
of DMAP was carried out, expecting the reaction accelera-
tion. However, the addition of base revealed to result in retar-
dation of the reaction, and 83% of starting material was
recovered after 5.0 h in CDCl3 at 140 ꢀC. When DBU was
used as a stronger amine base, the result was the same and
almost all the starting material was recovered. In both cases,
more than 18 h was needed to proceed the reaction
+
-
M
O
+
-
Ph
OH
RO M
M
N
Ph
Ph
-
+
O
S
N
S
N
S
S
S
S
2a-2
2a-3
2a-1
-
+
stabilization by
S
β
-sulfur atoms ?
M=K or Na
S
M
N
S
N
S
O
Ph
OH
+
Ph
7a'
3
4a
Scheme 3.

N. Yamada et al. / Tetrahedron 63 (2007) 3408–3414
3411
2.4. Synthetic application for several olefin syntheses
60 and also by preparative layer chromatography using silica
gel 60 PF254 with UV detection. All the reagents were of high-
est quality and further purified by distillation or recrystalliza-
tion. The solvents were further purified by general method.
In order to study the scope and limitations, we prepared
several b-hydroxysulfides 2 with several substituents at a-
or b-position and studied their thermolysis under the same
conditions. The results are summarized in Table 4. All reac-
tions are found to afford the corresponding olefins 5 in good
to excellent yields. In the case of 2i (entry 5), the dehydration
product 8 was also formed in a low yield.
4.2. General procedure for the preparation
of b-ketosulfides 1a–h
To a mixture of heterocyclic mercaptan (1 mmol) and a-
haloketones (1 mmol) in dichloromethane (10 ml) was
added dry triethylamine (0.5 ml) with stirring at rt under
N2. After the starting materials were consumed, the solvent
and excess triethylamine were evaporated off, and the resi-
due was dissolved in dichloromethane. The organic layer
was washed with 10 ml of brine and dried over anhydrous
MgSO4. Then, the solvent was removed to afford crude b-
ketosulfides 1a–h, which were purified by flash column
chromatography.
Table 4. Thermal reactions of 2-benzothiazolyl sulfides having several
substituents at a- and b-positiona
R2
OH
BtzS
R3
Btz
S
+
+
5
3
R3
CDCl3
140 °C, 5 h
R1
R2
R1
8
2b-e, 2i
Btz = 2-benzothiazolyl
Entry R1 R2
R3
Yield (%)b
4.2.1. 2-Benzothiazolyl phenacyl sulfide (1a). Yield 93%;
mp 109–111 ꢀC (colorless needles from CH2Cl2–diethyl-
ether–hexane); 1H NMR (CDCl3): d 4.98 (s, 2H), 7.28
(t, J¼7.6 Hz, 1H), 7.40 (t, J¼7.6 Hz, 1H), 7.52 (t,
J¼8.0 Hz, 2H), 7.61–7.65 (m, 1H), 7.75 (d, J¼8.0 Hz,
1H), 7.81 (d, J¼8.0 Hz, 1H), 8.08–8.10 (m, 2H); 13C NMR
(CDCl3): d 41.0, 121.1, 121.5, 124.4, 126.0, 128.6, 128.8,
133.8, 135.4, 135.5, 152.8, 165.2, 192.9; IR (KBr): n¼
1660 cmꢁ1. Anal. Calcd for C15H11NOS2: C, 63.13; H,
3.89; N, 4.91. Found: C, 63.20; H, 3.93; N, 4.95.
3
5
8
1
2
3
H
H
1-Nap
2-Nap
H
H
H
2b
2c
Quant.c Quant.c
0
0
0
92
86
88
Ph Ph
2dd 95
4
5
H
H
2e
96
77
91
82
0
5
O
Ph Ph
Ph 2i
a
b
c
d
In sealed tubes.
Isolated yield.
4.2.2. 2-Benzothiazolyl 1-naphthonyl sulfide (1b). Yield
85%; mp 122–123 ꢀC (white crystal from CH2Cl2–diethyl-
ether–hexane); H NMR (CDCl3): d 4.96 (s, 2H), 7.26–
Determined by 1H NMR.
Diastereomeric mixture (6:1).
1
7.30 (m, 1H), 7.35–7.39 (m, 1H), 7.52–7.60 (m, 3H), 7.74
(t, J¼8.0 Hz, 2H), 7.88–7.90 (m, 1H), 8.03 (d, J¼8.4 Hz,
1H), 8.11 (d, J¼7.2 Hz, 1H), 8.61 (d, J¼7.6 Hz, 1H); 13C
NMR (CDCl3): d 43.3, 121.1, 121.5, 124.3, 124.4, 125.9,
126.0, 126.7, 128.1, 128.2, 128.4, 130.3, 133.4, 134.0, 134.4,
135.6, 152.9, 165.1, 196.2; IR (KBr) n¼1661 cmꢁ1. Anal.
Calcd for C19H13NOS2: C, 68.03; H, 3.91; N, 4.18. Found:
C, 67.93; H, 4.01; N, 4.28.
3. Conclusion
Thermolysis of b-hydroxysulfides bearing benzothiazoles
2a–f afforded 3 and the corresponding olefins 5a–f, i in
good to excellent yields, respectively. The reactions are con-
sidered to proceed via five-membered spiro intermediate 6
by the ipso-addition of hydroxy group at b-position to NC
double bond of benzothiazole, followed by the formation
of 2-hydroxybenzothiazole (3) and olefin 5 generated by
thermal desulfurization of thiirane 4a. Thermal reactions
of b-hydroxysulfides are useful in olefin synthesis, and in
addition, further purification of olefins is very easy by silica
flash column chromatography. Additionally, this methodology
does not require any strong acid, unstable toxic metallic
reagents, or other expensive reagents.
4.2.3. 2-Benzothiazolyl 2-naphthonyl sulfide (1c). Yield
84%; mp 146–147 ꢀC (white solid from CH2Cl2–diethyl-
ether–hexane); H NMR (CDCl3): d 5.09 (s, 2H), 7.29 (t,
1
J¼7.8 Hz, 1H), 7.40 (t, J¼7.6 Hz, 1H), 7.55–7.65 (m, 2H),
7.74 (d, J¼8.0 Hz, 1H), 7.82–7.99 (m, 4H), 8.09 (dd,
J¼8.8, 2.0 Hz, 1H); 13C NMR (CDCl3): d 40.9, 121.1,
121.5, 123.9, 124.4, 126.1, 127.0, 127.8, 128.7, 128.9, 129.7,
130.6, 132.4, 132.8, 135.5, 135.9, 152.9, 165.3, 193.0; IR
(KBr): n¼1688 cmꢁ1. Anal. Calcd for C19H13NOS2: C,
68.03; H, 3.91; N, 4.18. Found: C, 67.73; H, 4.09; N, 4.03.
4. Experimental
4.1. General
4.2.4. 2-Benzothiazolyl a-phenylphenacyl sulfide (1d).
Yield 85%; mp 116–118 ꢀC (white crystal from CH2Cl2–di-
ethylether–hexane); 1H NMR (CDCl3): d 6.95 (s, 1H), 7.24–
7.38 (m, 5H), 7.44 (t, J¼7.6 Hz, 2H), 7.55 (t, J¼8.2 Hz, 3H),
7.71 (d, J¼8.0 Hz, 2H), 8.07 (d, J¼6.8 Hz, 2H); 13C NMR
(CDCl3): d 58.2, 121.1, 121.5, 124.3, 125.9, 128.6, 128.7,
129.0, 129.1, 129.2, 133.4, 134.6, 135.6, 152.8, 164.9,
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 Microanalytical Laboratory of the Department of Material
SystemsEngineeringandLifeScience, UniversityofToyama.
All the reactions were monitored with TLC and the products
were separated by column chromatography using silica gel
194.3; IR (KBr): n¼1683 cmꢁ1
.
Anal. Calcd for
C21H15NOS2: C, 69.78; H, 4.18; N, 3.87. Found: C, 69.70;
H, 4.22; N, 3.85.

3412
N. Yamada et al. / Tetrahedron 63 (2007) 3408–3414
4.2.5. 2-Benzothiazolyl 2-dibenzofuranoyl sulfide (1e).
Yield 80%; mp 157–158 ꢀC (white solid from CH2Cl2–
diethylether–hexane); H NMR (CDCl3): d 5.09 (s, 1H),
1H), 5.20 (dd, J¼8.0, 2.8 Hz, 1H), 7.29–7.48 (m, 7H), 7.75
(d, J¼8.0 Hz, 1H), 7.90 (d, J¼8.4 Hz); 13C NMR (CDCl3):
d 42.7, 73.7, 121.1, 121.3, 124.6, 125.8, 126.3, 127.8,
1
7.28–7.32 (m, 1H), 7.38–7.43 (m, 2H), 7.50–7.54 (m, 1H),
7.61 (d, J¼8.0 Hz, 3H), 7.64 (d, J¼8.8 Hz, 1H), 7.75 (d,
J¼8.4 Hz, 1H), 7.85 (d, J¼8.4 Hz, 1H), 7.97–8.00 (m,
1H), 8.23 (dd, J¼8.8, 2.0 Hz, 1H), 8.72 (d, J¼1.6 Hz, 1H);
13C NMR (CDCl3): d 41.0, 111.9, 112.0, 121.0, 121.4,
122.1, 123.5 (2C), 124.5, 124.8, 126.1, 128.15, 128.2,
130.6, 135.5, 152.7, 156.9, 159.3, 165.5, 192.2; IR (KBr):
n¼1674 cmꢁ1. Anal. Calcd for C21H15NO2S2: C, 67.18; H,
3.49; N, 3.73. Found: C, 67.08; H, 3.60; N, 3.73.
128.5, 135.5, 142.8, 152.4, 167.8; IR (KBr): n¼3233 cmꢁ1
.
Anal. Calcd for C15H11NOS2: C, 62.69; H, 4.56; N, 4.87.
Found: C, 62.77; H, 4.56; N, 4.87.
4.3.2. 2-Benzothiazolyl 2-hydroxy-2-(1-naphthyl)ethyl
sulfide (2b). Yield 92%; mp 89–91 ꢀC (colorless needles
from CH2Cl2–hexane); 1H NMR (CDCl3): d 3.53 (dd,
J¼14.8, 8.0 Hz, 1H), 3.98 (dd, J¼14.4, 2.0 Hz, 1H), 6.01
(dd, J¼14.0, 2.0 Hz, 1H), 7.35 (td, J¼8.0, 1.2 Hz, 1H),
7.45–7.54 (m, 3H), 7.60 (td, J¼8.0, 1.2 Hz, 1H), 7.78 (d,
J¼8.0 Hz, 1H), 7.81 (d, J¼8.0 Hz, 1H), 7.87–7.91 (m,
2H), 7.97 (d, J¼8.4 Hz, 1H), 8.31 (d, J¼8.8 Hz, 1H); 13C
NMR (CDCl3.): d 42.2, 70.4, 121.2, 121.3, 123.0, 123.3,
124.7, 125.5, 125.6, 126.26, 126.35, 128.3, 129.0, 130.1,
133.8, 135.4, 138.3, 152.4, 167.7; IR (KBr): n¼3316,
3248 cmꢁ1. Anal. Calcd for C19H15NOS2: C, 67.62; H,
4.48; N, 4.15. Found: C, 67.79; H, 4.55; N, 4.14.
4.2.6. 5-(4-Methyl)-4H-1,2,4-triazolyl 2-naphthonyl sul-
fide (1f). Yield 96%; mp 163–165 ꢀC (white solid from
CH2Cl2–diethylether–hexane); H NMR (CDCl3): d 3.65
1
(s, 3H), 5.01 (s, 2H), 7.56–7.65 (m, 2H), 7.89 (dd, J¼11.6,
8.4 Hz, 2H), 7.98 (d, J¼8.4 Hz, 1H), 8.04 (dd, J¼8.6,
1.8 Hz, 1H), 8.17 (s, 1H), 8.54 (s, 1H); 13C NMR (CDCl3):
d 31.0, 42.1, 123.6, 127.1, 127.7, 128.7, 129.0, 129.7,
130.7, 132.2, 132.3, 135.8, 145.2, 150.2, 192.9; IR (KBr):
n¼1685 cmꢁ1. Anal. Calcd for C15H13N3OS: C, 63.58; H,
4.62; N, 14.83. Found: C, 63.58; H, 4.57; N, 14.82.
4.3.3. 2-Benzothiazolyl 2-hydroxy-2-(2-naphthyl)ethyl
sulfide (2c). Yield 95%; mp 80–81 ꢀC (pale yellow solid
from CH2Cl2–diethylether–hexane); 1H NMR (CDCl3):
d 3.51–3.71 (m, 2H), 5.26 (dd, J¼7.8, 2.6 Hz, 1H), 7.23 (t,
J¼7.4 Hz, 1H), 7.33–7.41 (m, 3H), 7.46 (dd, J¼8.4,
1.6 Hz, 1H), 7.65 (d, J¼8.0 Hz, 1H), 7.74 (t, J¼7.6 Hz,
3H), 7.83 (d, J¼11.2 Hz, 1H); 13C NMR (CDCl3): d 42.7,
73.8, 121.0, 121.3, 123.8, 124.6, 124.7, 125.9, 126.1, 126.3,
127.7, 128.0, 128.3, 133.0, 133.2, 135.4, 140.2, 152.3,
167.9; IR (KBr): n¼3430, 3051 cmꢁ1. Anal. Calcd for
C19H15NOS2: C, 67.62; H, 4.48; N, 4.15. Found: C, 67.63;
H, 4.57; N, 4.12.
4.2.7. 5-(1-Phenyl)-1H-1,2,3,4-tetrazolyl 2-naphthonyl
sulfide (1g). Yield 99%; mp 122–123 ꢀC (white solid from
CH2Cl2–diethylether–hexane); H NMR (CDCl3): d 5.24
1
(s, 2H), 7.54–7.67 (m, 7H), 7.90 (d, J¼8.0 Hz, 1H), 7.93
(d, J¼8.4 Hz, 1H), 8.01 (d, J¼8.0 Hz, 1H), 8.06 (dd, J¼
1.6, 8.4 Hz, 1H), 8.61 (s, 1H); 13C NMR (CDCl3): d 42.8,
123.5, 123.8, 127.2, 127.8, 129.2, 129.9, 130.3, 130.8, 132.1,
132.4, 133.5, 136.0, 153.6, 192.1; IR (KBr): n¼1673 cmꢁ1
.
Anal. Calcd for C19H14N4OS: C, 65.88; H, 4.07; N, 16.17.
Found: C, 65.66; H, 4.21; N, 16.12.
4.3.4. 2-Benzothiazolyl 2-deutryl-2-hydroxy-2-(1-naph-
thyl)ethyl sulfide (2c0). Yield 95%; 1H NMR (CDCl3):
d 3.65 (d, J¼14.8 Hz, 1H), 3.80 (d, J¼14.8 Hz, 1H), 7.32–
7.36 (m, 1H), 7.44–7.51 (m, 3H), 7.55–7.58 (m, 1H), 7.60
(d, J¼8.4 Hz, 1H), 7.83–7.88 (m, 3H), 7.93–7.95 (m, 2H).
4.2.8. 2-Pyridyl 2-naphthonyl sulfide (1h). Yield 74%; mp
89–90 ꢀC (yellow crystal from CH2CH2–hexane); 1H NMR
(CDCl3): d 4.83 (s, 2H), 6.98 (ddd, J¼8.4, 5.2, 1.2 Hz, 1H),
7.25–7.27 (m, 1H), 7.45–7.50 (m, 1H), 7.52–7.62 (m, 2H),
7.88 (t, J¼4.8 Hz, 2H), 8.08 (dd, J¼4.8, 1.6 Hz, 1H),
8.36–8.38 (m, 1H), 8.62 (s, 3H); 13C NMR: d 37.0, 119.8,
122.2, 124.2, 126.7, 127.7, 128.4, 128.4, 129.6, 130.4, 132.4,
133.3, 135.6, 136.0, 149.2, 156.9, 194.5; IR (KBr): n¼
1680 cmꢁ1. Anal. Calcd for C17H13NOS: C, 73.09; H,
4.69; N, 5.01. Found: C, 73.13; H, 4.77; N, 4.92.
4.3.5. 2-Benzothiazolyl (1,2-diphenyl-2-hydroxy)ethyl
sulfide (2d, diastereomeric mixture). Yield 90%; dia-
1
stereomeric mixtures A and B (ratio of A/B, 1.0/6.0 by H
NMR) were separated by the repeated silica gel preparative
thin layer chromatography. Diastereomeric mixtures A and
1
B showed the following H and 13C NMR spectra, respec-
tively.
4.3. General procedure for the preparation
of b-hydroxysulfides 2a–h
Diastereomeric mixture A: colorless oil; 1H NMR (CDCl3):
d 3.78 (br, 1H), 5.28 (d, J¼4.4 Hz, 1H), 5.32 (d, J¼4.4 Hz,
1H), 7.08–7.15 (m, 10H), 7.19 (t, J¼7.6 Hz, 1H), 7.32 (t,
J¼7.6 Hz, 1H), 7.61 (d, J¼8.0 Hz, 1H), 7.81 (d, J¼8.0 Hz,
1H); 13C NMR (CDCl3): d 59.5, 76.5, 121.0, 121.6, 124.5,
126.1, 126.9, 127.8 (2C), 127.9, 128.1, 129.2, 135.4, 136.2,
140.2, 152.6, 166.1; IR (KBr): n¼3350, 3057, 3027, 1453,
To a solution of sodium borohydride (1 mmol) in THF–
methanol (1:1) was added sulfides 1a–h (1 mmol) in THF
with stirring at rt under N2, and the reaction mixture was
stirred until the starting b-ketosulfides disappeared. To the
reaction mixture was added AcOEt and washed with brine.
The aqueous layer was extracted with AcOEt. The combined
organic layer was dried over anhydrous MgSO4. Then, the
solvent was removed to afford crude product. Purification
by flash column chromatography on silica gel or recrystalli-
zation yielded pure b-hydroxysulfides 2a–h.
1424 cmꢁ1
.
Diastereomeric mixture B: white solid; mp 120–122 ꢀC
(white solid from AcOEt–hexane), 1H NMR (CDCl3):
d 5.39 (d, J¼4.4 Hz, 1H), 5.41 (d, J¼4.4 Hz, 1H), 7.16–
7.24 (m, 10H), 7.30 (t, J¼7.8 Hz, 1H), 7.43 (t, J¼7.8 Hz,
1H), 7.71 (d, J¼8.0 Hz, 1H), 7.91 (d, J¼8.0 Hz, 1H); 13C
NMR (CDCl3): d 61.5, 78.8, 121.0, 121.5, 124.7, 126.2,
4.3.1. 2-Benzothiazolyl 2-hydroxyphenethyl sulfide (2a).
Yield 84%; mp 82–83 ꢀC (white solid from CH2Cl2–hex-
ane); 1H NMR (CDCl3): d 3.53–3.74 (m, 2H), 5.03 (s,

N. Yamada et al. / Tetrahedron 63 (2007) 3408–3414
3413
126.7, 127.7, 127.9, 128.0, 128.3, 128.5, 135.5, 137.8, 141.6,
152.3, 167.6; IR (KBr): n¼3307, 3056, 3028, 1453,
1423 cmꢁ1. Anal. Calcd for C21H17NOS2: C, 69.39; H,
4.71; N, 3.85. Found: C, 69.49; H, 4.89; N, 3.95.
was removed to afford crude 2i, which was purified by re-
crystallization from dichloromethane, diethylether, and hex-
ane at rt with seeding. Yield 95%; mp 144–146 ꢀC; 1H NMR
(CDCl3): d 3.83 (br, 1H), 6.17 (s, 1H), 7.02–7.13 (m, 6H),
7.19–7.32 (m, 6H), 7.37–7.41 (m, 3H), 7.63–7.66 (m, 1H),
7.68–7.71 (m, 2H), 7.89–7.92 (m, 2H); 13C NMR (CDCl3):
d 61.2, 81.2, 120.9, 121.6, 124.2, 125.9, 126.1, 126.7,
127.29, 127.31, 127.6, 127.7, 128.2, 130.2, 135.7, 138.1,
4.3.6. 2-Benzothiazolyl 2-(2-dibenzofuranyl)-2-hydroxy-
ethyl sulfide (2e). Yield 94%; mp 108–110 ꢀC (white solid
from CH2Cl2–hexane); 1H NMR (CDCl3): d 3.64 (dd,
J¼14.4, 8.4 Hz, 1H), 3.79 (dd, J¼14.4, 3.2 Hz, 1H), 4.89
(br, 1H), 5.38 (dd, J¼8.4, 6.0 Hz, 1H), 7.31–7.36 (m, 2H),
7.43–7.47 (m, 2H), 7.51–7.57 (m, 3H), 7.75 (d, J¼8.0 Hz,
1H), 7.94 (t, J¼7.6 Hz, 1H), 7.10 (m, 1H); 13C NMR
(CDCl3): d 43.2, 73.8, 111.5, 111.7, 118.1, 120.7, 121.1,
121.3, 122.7, 124.1, 124.4, 124.8, 125.0, 126.4, 127.2,
135.3, 137.5, 152.1, 155.8, 156.6, 168.1; IR (KBr):
n¼3328, 3058 cmꢁ1. Anal. Calcd for C21H15NO2S2: C,
66.82; H, 4.01; N, 3.79. Found: C, 66.35; H, 4.17; N, 3.57.
144.4, 145.5, 152.9, 165.1; IR (KBr): n¼3328, 3058 cmꢁ1
.
Anal. Calcd for C21H15NOS2: C, 73.77; H, 4.82; N, 3.19.
Found: C, 73.60; H, 5.09; N, 3.04.
4.4. Thermolysis of 2-benzothiazolyl b-hydroxy-
phenethyl sulfide (2a) at neat conditions
To a 2 ml of Pyrex tube was added 50 mg (0.175 mmol) of
sulfide, and this tube was sealed after the replacement with
N2. The heating at 200 ꢀC for 30 min followed by separation
with preparative TLC, hexane–AcOEt (5/1), gave 24.4 mg
of 2-hydroxybenzothiazole (9) in 92% yield as white solid
and 16.6 mg of volatile mixture.
4.3.7. 4-(4-Methyl)-4H-1,2,4-triazolyl 2-hydroxy-2-(2-
naphthyl)ethyl sulfide (2f). Yield 90%; mp 97–98 ꢀC (white
solid from CH2Cl2–ether–hexane); 1H NMR (CDCl3): d 3.47
(s, 3H), 3.50 (dd, J¼14.4, 8.0 Hz, 2H), 3.64 (dd, J¼14.4,
3.2 Hz, 2H), 4.96 (br, 1H), 5.28 (dd, J¼8.0, 3.2 Hz, 2H),
7.44–7.47 (m, 2H), 7.50 (dd, J¼8.8, 1.6 Hz, 1H), 7.79–8.82
(m, 3H), 7.89 (s, 1H), 8.04 (s, 1H); 13C NMR (CDCl3):
d 31.0, 41.8, 73.4, 123.9, 124.7, 125.8, 126.1, 127.6, 128.0,
128.1, 132.9, 133.1, 140.1, 145.0, 151.8; IR (KBr):
4.5. Thermolysis of 2-(2-naphthyl)-2-hydroxyethyl
sulfide bearing several heteroaromatics
2-Benzothiazolyl 2-hydroxy-2-(2-naphthyl)ethyl sulfide
(2c) of 10 mg dissolved in CDCl3 was poured into a 2 ml
Pyrex tube and this tube was sealed under N2. After heating
the sample at 140 ꢀC for 5 h, the crude mixture was mea-
sured by 1H NMR directly.
n¼3181, 1510, 1079 cmꢁ1
. HRMS (EI) calcd for
C15H15N3OS: 285.0936. Found: m/z 285.0923 (M+).
4.3.8. 5-(1-Phenyl)-1H-1,2,3,4-tetrazolyl 2-hydroxy-2-(2-
naphthyl)ethyl sulfide (2g). Yield 94%; mp 120–122 ꢀC
(white crystal from CH2Cl2–diethylether–hexane); 1H NMR
(CDCl3): d 3.18 (br, 1H), 3.60 (dd, J¼14.0, 8.4 Hz, 1H), 3.90
(dd, J¼14.0, 3.2 Hz, 1H), 5.36 (dd, J¼8.4, 3.2 Hz, 1H) 7.46–
7.52 (m, 8H), 7.82–7.86 (m, 3H), 7.91 (s, 1H); 13C NMR
(CDCl3): d 41.8, 72.9, 123.6, 123.8, 124.8, 126.2, 126.3,
127.7, 128.1,128.5,129.8,130.17,133.18,133.5,139.2, 154.6;
IR (KBr): n¼3497 cmꢁ1. Anal. Calcd for C19H14N4OS: C,
65.50; H, 4.63; N, 16.08. Found: C, 65.49; H, 4.83; N, 15.99.
4.6. Time dependence study of thermolysis
of 2-benzothiazolyl b-hydroxyphenethyl sulfide 2a
To 10 mg of sulfide dissolved in 1.0 ml of CDCl3 was added
1.0 equiv of mesitylene, and this reaction mixture was put
into a 2 ml Pyrex tube sealed under N2. After sealing the tube
followed by heating each samples at 140 ꢀC for 0.5, 1.0, 1.5,
2.0, 2.5, 3.0, 4.0, and 5.0 h, the change of the component of
reaction mixture was measured by 1H NMR directly.
4.3.9. 2-Pyridyl 2-hydroxy-2-(2-naphthyl)ethyl sulfide
(2h). Yield 93%; mp 57–58 ꢀC (white crystal from
CH2Cl2–diethylether–hexane); H NMR (CDCl3): d 3.46
4.6.1. 1-Deuterium-1-(2-naphthyl) thiirane (4c0). 1H NMR
(CDCl3): d 2.76 (s, 1H), 2.94 (s, 1H), 7.29 (dd, J¼8.8,
2.4 Hz, 1H), 7.43–7.52 (m, 3H), 7.73–7.85 (m, 4H).
1
(dd, J¼14.4, 7.6 Hz, 1H), 3.50 (dd, J¼14.4, 3.2 Hz, 1H),
5.25 (dd, J¼7.6, 3.2 Hz, 1H), 6.65 (br, 1H), 7.03 (ddd,
J¼7.2, 5.2, 0.8 Hz, 2H), 7.27 (d, J¼8.0 Hz, 2H), 7.41–7.48
(m, 3H), 7.53 (dd, J¼8.4, 1.6 Hz, 1H), 7.80–7.84 (m, 3H),
7.93 (s, 1H), 8.41–8.43 (m, 1H); 13C NMR (CDCl3):
d 40.8, 74.5, 120.1, 123.0, 124.1, 124.6, 125.6, 125.9, 127.6,
127.9, 128.0, 132.9, 133.2, 136.6, 141.3, 148.7, 159.0; IR
(KBr): n¼3292 cmꢁ1. Anal. Calcd for C17H15NOS: C,
72.57; H, 5.37; N, 4.98. Found: C, 72.83; H, 5.56; N, 5.00.
4.6.2. 1-Deuterium-1-(2-naphthyl) ethylene (5c0). 1H
NMR (CDCl3): d 5.33 (s, 1H), 5.86 (t, J¼2.4 Hz, 1H),
7.41–7.48 (m, 2H), 7.63 (dd, J¼8.8, 1.6 Hz, 1H), 7.74 (s,
1H), 7.78–7.82 (m, 3H).
4.6.3. 2-Vinyldibenzofuran15 (5e). 1H NMR (CDCl3):
d 5.27 (d, J¼10.8 Hz, 1H), 5.79 (d, J¼13.6 Hz, 1H), 6.87
(dd, J¼13.6, 10.8 Hz, 1H), 7.34 (t, J¼7.6 Hz, 1H), 7.43–
7.47 (m, 1H), 7.51–7.56 (m, 3H), 7.94 (d, J¼7.6 Hz, 1H),
7.96 (s, 1H); 13C NMR (CDCl3): d 111.6, 111.7, 113.0,
118.3, 120.7, 122.8, 124.1, 124.5, 127.2, 132.7, 136.7, 155.9,
156.6. HRMS (EI) calcd for C14H10O: 194.0727. Found: m/z
194.0732 (M+).
4.3.10. 2-Benzothiazolyl 2-hydroxy-1,2,2-triphenylethyl
sulfide (2i). To a solution of 2-benzothiazolyl a-phenylphen-
acyl sulfide (1d) (890 mg, 2.46 mmol) in 10 ml of anhy-
drous THF was added 1.1 equiv of phenyl magnesium
bromide solution in anhydrous THF with stirring at rt under
N2. After 6 h, 5.0 ml of 1.0 M aqueous HCl was added
slowly to complete the reaction. The mixture was extracted
with AcOEt (20 mlꢂ4) and 50 ml of brine. The combined
organic phase was dried over anhydrous MgSO4. The solvent
4.6.4. 2-Triphenylvinylsulfanylbenzothiazole (8). Mp
137–139 ꢀC (pale yellow solid); 1H NMR (CDCl3):
d 7.02–7.05 (m, 2H), 7.07–7.13 (m, 6H), 7.22–7.24 (m,
1H), 7.26–7.31 (m, 3H), 7.34–7.37 (m, 1H), 7.38–7.43 (m,

3414
N. Yamada et al. / Tetrahedron 63 (2007) 3408–3414
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Tetrahedron Lett. 1984, 25, 4775; (b) Shimagaki, M.; Maeda,
T.; Hori, I.; Oishi, T. Tetrahedron Lett. 1984, 25, 4779;
(c) Yra, T.; Iwasawa, N.; Clark, R.; Mukaiyama, T. Chem.
Lett. 1986, 1809; (d) Yamashita, M.; Kitagawa, K.; Ohara,
T.; Iida, Y.; Masumi, A.; Kawasaki, I.; Ohta, S. Chem. Lett.
1993, 653; (e) Posner, G. H.; Rogers, D. Z. J. Am. Chem.
Soc. 1977, 8208; (f) Vougioukas, A. E.; Kagan, H. B.
Tetrahedron Lett. 1987, 28, 6065; (g) Iqbal, J.; Pandey, A.;
Shukla, A.; Srivastava, R. Tetrahedron 1990, 46, 6423; (h)
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2H), 7.45–7.47 (m, 2H), 7.66–7.69 (m, 1H), 7.79–7.82 (m,
1H); IR (KBr): n¼3377, 3050, 1489, 747 cmꢁ1. HRMS (EI)
calcd for C27H19NS2: 421.0959. Found: m/z 421.0973 (M+).
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