NBS/DMSO-mediated synthesis of (2,3-dihydrobenzo[b] [1,4]oxathiin-3-yl)methanols from aryloxymethylthiiranes

Article abstract of DOI:10.1039/c8nj01117f

(2,3-Dihydrobenzo[b][1,4]oxathiin-3-yl)methanols were synthesized via reactions of aryloxymethylthiiranes and N-bromosuccinimide (NBS) in DMSO under microwave irradiation. The reaction mechanism was proposed as an intramolecular aromatic electrophilic substitution of 1-bromo-2-(aryloxymethyl)thiiran-1-iums, generated from aryloxymethylthiiranes and NBS, and the subsequent DMSO nucleophilic ring opening reaction of thiiran-1-iums followed by the water displacement. The current method provides a direct and simple strategy in the efficient preparation of (2,3-dihydrobenzo[b][1,4]oxathiin-3-yl)methanols from readily available aryloxymethylthiiranes.

Full text of DOI:10.1039/c8nj01117f

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ISSN 1144-0546
PAPER
Jason B. Benedict et al.
The role of atropisomers on the photo-reactivity and fatigue of
diarylethene-based metal–organic frameworks
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DOI: 10.1039/C8NJ01117F
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NBS/DMSO-mediated synthesis of (2,3-dihydrobenzo[b][1,4]
oxathiin-3-yl)methanols from aryloxymethylthiiranes
Jun Dong, Jiaxi Xu*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Abstract: (2,3-Dihydrobenzo[b][1,4]oxathiin-3-yl)methanols were synthesized via reactions of aryloxymethylthiiranes and
N-bromosuccinimide (NBS) in DMSO under microwave irradiation. The reaction mechanism was proposed as an
intramolecular aromatic electrophilic substitution of 1-bromo-2-(aryloxymethyl)thiiran-1-iums, generated from
aryloxymethylthiiranes and NBS, and subsequent DMSO nucleophilic ring opening reaction of thiiran-1-iums, followed by
the water displacement. The current method provides a direct and simple strategy in efficient preparation of (2,3-
dihydrobeno[b][1,4]oxathiin-3-yl)methanols from readily available aryloxymethylthiiranes.
Introduction
2,3-Dihydrobenzo[b][1,4]oxathiine derivatives have received great
attention in chemical, medicinal, and pharmaceutical research.
During the last decades their syntheses as well as applications as
antioxidants, hypertensive agents, estrogen receptor modulators,
adrenoreceptor antagonists, artificial sweetener, and anticancer
agents (Figure 1) have been reported in dozens of papers and
patents.1 Many synthetic methods have been developed for the
preparation of 2,3-dihydrobenzo[b][1,4]oxathiines, especially 2-
Figure 1. Sweetener and anticancer agents derived from 3-substituted
2,3-dihydrobenzo[b][1,4]oxathiines
Although
3-monosubstituted
or
3,3-disubstituted
2,3-
monosubstituted
and
2,3-disubstituted
2,3-
dihydrobenzo[b][1,4]oxathiines have been widely applied in organic
synthesis and medicinal chemistry, their synthetic methods are very
dihyrobenzo[b][1,4]oxathiines.2 However, only limited methods can
be used to achieve the synthesis of 3-substituted 2,3-
dihydrobenzo[b][1,4]oxathiines.
limited
to
date.
Several
synthetic
methods
for
benzo[b][1,4]oxathiines have been developed. a) 3-Substituted 2,3-
dihydrobenzo[b][1,4]oxathiine derivative, anticancer agent 6-
chloro-3-(2,3-dihydrobenzo[b][1,4]oxathiin-3-ylmethyl)purine, was
obtained by applying a standard Mitsunobu protocol that led to a
six-membered
ring
contraction
from
3,4-dihydro-2H-
benzo[b][1,5]oxathiepin-3-ol via an episulfonium intermediate.3 b)
3-Chloromethyl-3-methyl-2,3-dihydrobenzo[b][1,4]oxathiines were
prepared by the reaction of several 2-methylallyl phenyl ethers with
sulfur
dichloride.4
c)
8-Chloro-7-methoxy-3-methyl-2,3-
dihydrobenzo[b][1,4]oxathiine was constructed from 2-[(2,3-
dichloro-4-methoxyphenyl)thio]propanol in the presence of sodium
hydride via an intramolecular aromatic nucleophilic substitution.5 d)
3-Aryl-2,3-dihydrobenzo[b][1,4]oxathiine was synthesized by the N-
bromosuccinimide (NBS)-promoted oxidative rearrangement of 1,3-
a.State Key Laboratory of Chemical Resource Engineering, Department of Organic
Chemistry, Faculty of Science, Beijing University of Chemical Technology, Beijing
100029, People’s Republic of China.
Email: jxxu@mail.buct.edu.cn.
Electronic Supplementary Information (ESI) available: [Copies of 1H and 13C NMR
spectra of unknown products 1, 2, and 3, and mass spectra of byproducts in
reaction mixture]. See DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
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oxathiospiro[4.5]decane derived from 2-aryl-2-mercaptoethanol product 2a was obtained when DBDMH was used (Table 1, entries
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and cyclohexanone (Scheme 1).6 In view of the importance of 2,3- 12 and 13). When the reaction time was incrDeOasI:e1d0.f1r0o3m9/C185NmJ0in11s1t7oF
dihydrobenzo[b][1,4]oxathiines and drawbacks of the reported 20 mins, the yield was slightly decreased (Table 1, entry 14 vs entry
synthetic methods, the efficient synthesis of these compounds is 5). The yield further decreased when oil-bath heating for 120 mins
still in high demand. Thiiranes have unique chemical properties and instead of microwave irradiation for 20 mins (Table 1, entry 15). The
have been of interest in our laboratory in recent years.7,8 They are yield also decreased when the reaction was conducted at 80 oC
readily available from the corresponding oxiranes. Thus, we under microwave irradiation (Table 1, entry 16). Considering the
envisioned that 2,3-dihydrobenzo[b][1,4]oxathiines should be generation of HBr in the reaction mixture (vide post), TEA and
synthesized from the ring expansion of aryloxymethylthiiranes. We, pyridine were added, respectively, as bases into the reaction
herein, present a new synthetic strategy for the preparation of (2,3- mixture. But no obvious impact on the yield was observed (Table 1,
dihydrobenzo[b][1,4]oxathiin-3-yl)methanols through the N- entries 17 and 18). The optimum reaction conditions were finally
o
bromosuccinimide-promoted ring expansion reactions of identified as follows: 1a:NBS = 1:1 in DMSO as solvent at 110 C for
aryloxymethylthiiranes in dimethyl sulfoxide (DMSO) under 15 mins microwave irradiation (Table 1, entry 5).
microwave conditions (Scheme 1).
Table 1. Optimization for the reaction of 2-(phenoxymethyl)thiirane
(1a) and NBSa
1a:NBS
Solvent
Time (min) Yieldb (%)
Entry
1
Temp (oC)
0
1:1
1:1
DMF
Toluene
DCE
110
110
110
110
110
110
110
110
110
110
110
110
110
110
110
80
15
2
0
15
3
0
1:1
15
4
0
1:1
MeCN
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
15
5
42
1:1
15
6
3
2:1
15
Scheme 1. Synthesis of 3-monosubstituted and 3,3-disubstituted 2,3-
dihydrobenzo[b][1,4]oxathiines.
7
mess
1:2
15
8
5
1:1.2
1:1.5
1:1c
1:1d
1:1e
1:1f
1:1
15
Results and discussion
9
7
15
At the outset of this study, 2-(phenoxymethyl)thiirane (1a) and NBS
(N-bromosuccinimide) were employed as the model reactants to
optimize reaction conditions (Table 1). Initially, we screened
solvents and found that DMF, toluene, DCE (1,2-dichloroethane),
and MeCN were unsuitable solvents to get the corresponding
product 2a (Table 1, entries 14). When DMSO was used as solvent,
product 2a was obtained in 42% yield (Table 1, entry 5). We further
optimized the reactant ratio of 1a:NBS and found that the yield
dropped sharply when 1a:NBS in 2:1 (Table 1, entry 6). When the
ratio of 1a:NBS was decreased to 1:2, the reaction system became
very complex because various brominated phenols generated (vide
post) (Table 1, entry 7). The reactions with ratios of 1a:NBS in 1:1.2
and 1:1.5 gave the product in 5% and 7% yields, respectively (Table
1, entries 8 and 9). It was noteworthy that no desired product was
generated when NCS (N-chlorosuccinimide) and NIS (N-
iodosuccinimide) were used as halogeniums (X+) instead of NBS
(Table 1, entries 10 and 11). The other choices of brominium (Br+),
which generated from KBr/K2S2O8, DBDMH (1,3-dibromo-5,5-
dimethyl hydantoin), were also attempted and only trace amount of
10
11
12
13
14
15g
16
17h
18i
0
15
0
15
0
15
trace
15
25
20
17
1:1
120
15
1:1
15
23
1:1
110
110
15
24
1:1
15
a) All reactions were conducted on a 0.25 mmol scale of 1a and NBS in 5 mL of
solvent in a 10 mL microwave tube and were stirred at 110 oC under microwave
2 | J. Name., 2012, 00, 1-3
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irradiation in a sealed vessel. b) Yield of isolated product. c) NCS instead of NBS.
d) NIS instead of NBS. e) KBr/K2S2O8 instead of NBS. f) DBDMH (1,3-dibromo-
5,5-dimethyl hydantoin) instead of NBS. g) Oil-bath heating instead of
microwave irradiation. h) TEA (28 mg, 0.28 mmol) was added as a base. i)
Pyridine (22 mg, 0.28 mmol) was added as a base.
View Article Online
DOI: 10.1039/C8NJ01117F
With the optimized reaction conditions, the reaction scope was
then evaluated (Table 2). Various aryloxymethylthiiranes 1 were
subjected to the reaction conditions with NBS in DMSO under
microwave irradiation. The results are presented in Table 2.
Phenoxymethylthiirane
(1a)
and
meta-
methylphenoxymethylthiirane (1c) produced the corresponding
products 2a, 2ca and 2cb in relatively higher yields because the
reactive positions locate on the ortho and para-positions of the
activating methyl group for substrate 1c. Two regioisomeric
products 2ca and 2cb were obtained from meta-
methylphenoxymethylthiirane (1c) due to the existence of two
different activated (ortho and para-)positions. However,
para/ortho-methylphenoxymethylthiiranes (1b and 1d) and para-
methoxyphenoxymethylthiirane (1e) gave rise to the corresponding
products 2b, 2d, and 2e in relatively lower yields because their
reaction positions are the meta-position of the methyl and methoxy
groups (Table 2). meta-Methyl and methoxy groups are deactivating
groups in the aromatic electrophilic substitution according to
Hammett constants. In comparison with monomethyl substituted
phenoxymethylthiiranes 1b-d, more electron-rich dimethyl
substituted phenoxymethylthiiranes 1f-g gave rise to the
corresponding products 2f-g in relatively higher yields. We further
extended thiiranes
naphthyloxymethylthiiranes,
(1h),
bromonaphthalen-2-yloxymethyl)thiirane (1j) generated the
corresponding products 2h-j in moderate yields. However, no
desired products were observed for electron-deficient 2-(4-
1
from phenoxymethylthiiranes to
(naphthalen-1-yloxymethyl)thiirane
aReaction conditions: Thiirane 1 (0.25 mmol) and NBS (0.25 mmol) were added
(naphthalen-2-yloxymethyl)thiirane
(1i),
and
(6-
in DMSO (5 mL) in a 10 mL microwave tube, then the reaction mixture was
o
stirred at 110 C for 15 mins under microwave irradiation in a sealed vessel. After
cooling water (30 mL) was added, the mixture was extracted with DCM (20 mL X
3), and the combined extracts were washed with brine, dried over anhydrous
sodium sulfate, and concentrated in vacuo, the resulting residue was purified by
silica gel column chromatography (200-300 mesh, hexanes-EtOAc, 10:1, v/v) to
afford the product 2. All yields are isolated yields.
chlorophenoxymethyl)thiirane
(1k)
and
2-(4-
bromophenoxymethyl)thiirane (1l) (Table 2). Geminal disubstituted
2-methyl-2-(3-methylphenoxymethyl)thiirane (1m) reacted with
NBS in DMSO to afford two isomeric corresponding products 2ma
and 2mb in low yields. Geminal disubstituted 2-methyl-2-
(naphthalen-2-yloxymethyl)thiirane (1n) gave product 2n in a
satisfactory yield. Similarly, geminal disubstituted 2,3-dimethyl-2-
(naphthalen-1-yloxymethyl)thiirane (1o) gave the corresponding
product 2o as expected.
To illustrate the reaction mechanism, we performed the
model reaction under the optimized conditions with treatment
with H2O18 (Scheme 2). After the reaction was complete, no O18-
2a was obtained on the basis of mass spectral analysis of
product 2a. However, the GC-MS analysis of the reaction
mixture indicated that the relative intensity of O18-DMSO at m/z
80 (compared with that of DMSO at m/z 78, the base peak)
increased slightly from original 4.7% (before the reaction) to the
current 7.6% (after the reaction). The results reveal that water
does not nucleophilically attacks the thiiran-1-nium in
intermediate B, generated from the aromatic electrophilic
substitution of the aryl group and 1-bromothiiran-1-ium ion A.
Instead, it should be that dimethylsulfoxide undergoes an ring
opening reaction of the thiiran-1-nium in intermediate B from
its less substituted ring carbon atom, leading to intermediate C.
Water attacks the sulfurium in intermediate C during treatment
with water to afford the desired product 2a (Scheme 3).
Table 2. Scope of substratesa
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stable aromatic para-bromophenol, which canViewbeArticfleuOrtnhliener
DOI: 10.1039/C8NJ01117F
brominated. 1-Thiabicyclo[1.1.0]butanium converts into thietan-3-
ol when treatment with water. Bromophenols were observed in
most reactions in GC-MS analysis.
To verify water attacking process, we designed and
Scheme 2. Designed experiment for investigating the water-participated
reaction step with H2O18.
conducted two reactions with benzylamine and thiophenol as
nucleophiles in the reaction of thiirane 1a and NBS. Both
benzylamine and thiophenol are stronger nucleophiles than
water. As expected, the corresponding amine and sulfide
Considering the reaction mechanism, the reaction of thiirane 1a
was selected as an example to illustrate the mechanism (Scheme 3).
First, thiirane 1a as a nucleophile attacks NBS to generate an
intermediate 1-bromothiiran-1-ium ion A, which further undergoes
an intramolecular aromatic electrophilic substitution to afford
intermediate B. DMSO undergoes a ring opening reaction of the
thiiran-1-nium in intermediate B from its less substituted ring
carbon atom, affording intermediate C. During workup, water
attacks the sulfurium in intermediate C, yielding intermediate D.
After proton transfer and loss of protonated DMSO, the desired
product 2a is generated (Scheme 3).
derivatives
were
not
observed.
Instead,
(2,3-
dihydrobenzo[b][1,4]oxathiin-3-yl)methanol
(2a),
N,N’-
dibenzylhydrazine, and 1,2-diphenyldisulfane were detected in
the reaction mixtures, respectively, by GC-MS analysis (Scheme
4). Both results support our proposed reaction mechanism.
Scheme 4. Designed reactions for investigation on the proposed
mechanism.
Scheme 3. Proposed mechanisms for the synthesis of (2,3-
dihydrobenzo[b][1,4]oxathiin-3-yl)methanol and the competitive side
reactions.
Scheme 5. Formation mechanisms of N,N’-dibenzylhydrazine and 1,2-
diphenyldisulfane.
Although the reaction conditions were carefully optimized, low to
good yields were obtained. The low yields are attributed to the
competitive side reaction, the bromination of the phenyl group. In
the presence of NBS, electron-rich phenoxy group can be
brominated on its para- or/and ortho-position(s). Herein, only para-
brominated product is shown, generating intermediate F, which
further undergoes an intramolecular nucleophilic displacement to
give rise to 4-bromo-2,5-cyclohexadienone (G) and 1-
thiabicyclo[1.1.0]butanium. G can further tautomerize into more
The formation mechanisms of N,N’-dibenzylhydrazine and
1,2-diphenyldisulfane were also proposed. Both benzylamine
and thiophenol as nucleophiles attack the sulfurium in
intermediate C to generate intermediates H and I, respectively,
after release of product 2a. Both benzylamine and thiophenol
further nucleophilically attack the nitrogen atom in
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intermediate
ARTICLE
H
and the sulfur atom in intermediate I,
residue was extracted with EtOAc (3 × 30 mL). The combined
View Article Online
DOI: 10.1039/C8NJ01117F
organic layers were washed with brine (20 mL), dried over
respectively, to afford N,N’-dibenzylhydrazine and 1,2-
diphenyldisulfane by loss of dimethyl sulfide and proton
(Scheme 5).
anhydrous Na2SO4, and concentrated under reduced pressure. The
obtained crude product was purified by column chromatography
(silica gel, petroleum ether–ethyl acetate (PE–EtOAc), 100:1, v/v) to
give pure oxirane 3. The analytical data of known oxiranes 3 are
identical to those reported previously.
Conclusions
In summary, we developed a direct and simple strategy for the
preparation of (2,3-dihydrobenzo[b][1,4]oxathiin-3-yl)methanols,
2-((2,4-Dimethylphenoxy)methyl)oxirane (3g)
important intermediates in medicinal chemistry. The method Colorless oil, 2.91 g, yield 33%, Rf = 0.30 (Hexanes/EtOAc = 20:1,
1
mainly utilized the reaction of aryloxymethylthiiranes and NBS in v/v). H NMR (400 MHz, CDCl3): δ 6.97 (s, 1H), 6.94 (d, J = 8.2 Hz,
DMSO under microwave irradiation, affording 3-monosubstituted, 1H), 6.72 (d, J = 8.2 Hz, 1H), 4.20 (dd, J = 11.2, 2.8 Hz, 1H), 3.96 (dd,
2,3- and 3,3-disubstituted 2,3-dihydrobenzo[b][1,4]oxathiines in J = 11.2, 5.5 Hz, 1H), 3.36 (dddd, J = 5.6, 4.0, 2.9, 2.9 Hz, 1H), 2.90
acceptable to good yields. The method also had advantages of (dd, J = 5.0, 4.1 Hz, 1H), 2.78 (dd, J = 5.0, 2.7 Hz, 1H), 2.27 (s, 3H),
cheap and easy access to raw materials, short reaction times, and 2.23 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 154.5, 131.6, 130.5, 126.9,
simple operation. The reaction mechanism was proposed.
126.8, 111.4, 68.9, 50.4, 44.7, 20.4, 16.1. IR (KBr): 2923, 1505, 1457,
+
862, 803 cm-1. HR-MS (ESI) m/z [M + H]+ calcd for C11H15O2 :
179.1067, found:179.1070..
Experimental
2-Methyl-2-((naphthalen-2-yloxy)methyl)oxirane (3n)
Unless otherwise noted, all materials were purchased from
commercial suppliers. Flash column chromatography was
performed using silica gel (normal phase, 200-300 mesh) from
Branch of Qingdao Haiyang Chemical Industry. Petroleum ether (PE)
used for column chromatography is 60−90 oC fraction, and the
removal of residue solvent was accomplished under rotovap.
Reactions were monitored by thin-layer chromatography on silica
gel GF254 coated 0.2 mm plates from Institute of Yantai Chemical
Industry. The plates were visualized under UV light, as well as other
TLC stains (10% phosphomolybdic acid in ethanol; 1% potassium
permanganate in water; 10 g of iodine absorbed on 30 g of silica
White solid, m.p. 80 – 80 oC. 2.91 g, yield 49%, Rf = 0.58
(Hexanes/EtOAc = 10:1, v/v). H NMR (400 MHz, CDCl3): δ 7.78 –
1
7.72 (m, 3H), 7.46 – 7.42 (m, 1H), 7.37 – 7.33 (m, 1H), 7.19 (dd, J =
8.9, 2.5 Hz, 2H), 7.14 (d, J = 2.3 Hz, 2H), 4.16 (d, J = 10.4 Hz, 2H),
4.07 (d, J = 10.4 Hz, 2H), 2.94 (d, J = 4.7 Hz, 1H), 2.78 (d, J = 4.7 Hz,
1H), 1.54 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 156.5, 134.4, 129.4,
129.1, 127.6, 126.8, 126.4, 123.8, 118.8, 106.9, 71.5, 55.5, 52.1,
18.6. IR (KBr): 2923, 1599, 1508, 1385 cm-1. HR-MS (ESI) m/z [M +
+
H]+ calcd for C14H15O2 : 215.1067, found: 215.1071.
1
gel). H and 13C NMR spectra were recorded on a Bruker 400 MHz
General procedure for the preparation of thiiranes 1a‒1g, 1m8d
spectrometer in CDCl3 with TMS as an internal standard, and the
chemical shifts (δ) are reported in parts per million (ppm). All
coupling constants (J) in H NMR spectra are absolute values given
A solution of oxirane 3 (24.0 mmol) and KSCN (9.31 g, 96.0 mmol) in
water (30.0 mL) was heated to 40 oC and stirred for 24 h at the
same temperature. The resulting mixture was diluted with EtOAc
and washed with brine. The organic phase was dried (Na2SO4) and
concentrated in vacuo. The residue was purified by column
chromatography (silica gel, hexanes) to give thiirane 1.
1
in hertz (Hz) with peaks labeled as singlet (s), broad singlet (brs),
doublet (d), triplet (t), quartet (q), and multiplet (m). The IR spectra
(KBr pellets,
v a Nicolet 5700 FTIR
[cm−1]) were taken on
spectrometer. HRMS measurements were carried out on an Agilent
LC/MSD TOF mass spectrometer. LRMS measurements were carried
out on Thermo Trace 1300/ISQ QD system. Melting points were
obtained on a Yanaco MP-500 melting point apparatus and are
uncorrected. All the microwave reactions were conducted in CEM
Discover SP microwave system equipped with an infrared
temperature detector.
Phenoxymethylthiirane (1a)
Colorless oil, 2.91 g, yield 88%, Rf = 0.62 (Hexanes/EtOAc = 10:1,
v/v). 1H NMR (400 MHz, CDCl3): δ 7.29 (t, J = 7.9 Hz, 2H), 6.97 (t, J =
7.6 Hz, 1H), 6.91 (d, J = 8.4 Hz, 2H), 4.22 (dd, J = 10.2, 5.4 Hz, 1H),
3.90 (dd, J = 10.2, 7.2 Hz, 1H), 3.30 ‒ 3.24 (m, 1H), 2.61 (d, J = 6.0 Hz,
1H), 2.33 (d, J = 5.2 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 158.4,
129.5, 121.2, 114.7, 72.5, 31.4, 24.0. GC-MS (EI) m/z = 166 (M)+ for
C9H10OS.
General procedure for synthesis of oxiranes 4a-c, 4h, and 4l, 4m-o
General procedure for the preparation of oxiranes 3
To a stirred solution of phenol (25.0 mmol) in ethanol (30 mL) was
added NaOH (30.0 mmol, 1.20 g). After stirring for 20 min at room
temperature, 2-(chloromethyl)oxirane (75.0 mmol, 6.94 g) or 2-
(chloromethyl)-2-methyloxirane (75.0 mmol, 7.99 g) was added
dropwise over 30 min. The resulting mixture was stirred at room
temperature for 24 h (TLC-monitoring). When the reaction was
complete, the solvent was removed under reduced pressure. The
(4-Methylphenoxy)methylthiirane (1b)
Colorless oil, 2.00 g, yield 56%, Rf = 0.91 (Hexanes/EtOAc = 5:1, v/v).
1H NMR (400 MHz, CDCl3): δ 7.07 (d, J = 8.4 Hz, 2H), 6.80 (d, J = 8.4
Hz, 2H), 4.18 (dd, J = 10.2, 5.6 Hz, 1H), 3.85 (dd, J = 10.2, 7.2 Hz, 1H),
3.27 ‒ 3.21 (m, 1H), 2.58 (d, J = 6.4 Hz, 1H), 2.31 ‒ 2.29 (m, 1H), 2.28
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(s, 3H). 13C NMR (101 MHz, CDCl3): δ 156.3, 130.5, 129.9, 114.6, 9.6 Hz, 1H), 2.52 (d, J = 1.0 Hz, 1H), 2.46 (t, J = 1.0 Hz, 1H), 2.32 (s,
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13
72.8, 31.4, 24.0, 20.4. GC-MS (EI) m/z = 180 (M)+ for C10H12OS.
3H), 1.74 (s, 3H). C NMR (101 MHz, CDCl3)D: OδI:11508.1.70,391/3C98.N6J1021191.72F,
121.9, 115.6, 111.5, 76.0, 42.4, 32.7, 23.4, 21.5. IR (KBr): 2920, 2854,
1561, 1504, 1383 cm-1. GC-MS (EI) m/z = 194 (M)+ for C11H14OS.
(3-Methylphenoxy)methylthiirane (1c)
General procedure for the preparation of thiiranes 1h‒1j, 1k-l8b
Colorless oil, 1.79 g, yield 50%, Rf = 0.62 (Hexanes/EtOAc = 10:1,
v/v). 1H NMR (400 MHz, CDCl3): δ 7.08 (t, J = 7.6 Hz, 1H), 6.70 (d, J =
7.6 Hz, 1H), 6.65 ‒ 6.61 (m, 2H), 4.11 (dd, J = 10.4, 5.6 Hz, 1H), 3.79 To a stirring solution of oxirane 4 (10 mmol) in MeOH (30 mL) was
(dd, J = 10.4, 7.2 Hz, 1H), 3.20 ‒ 3.14 (m, 1H), 2.51 (d, J = 6.4 Hz, 1H), added thiourea (1.52 g, 20 mmol); when it was completely dissolved,
2.24 (s, 3H), 2.23 (d, J = 5.6 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ the resulting solution was refluxed for 1.5 h, After removal of
158.4, 139.5, 129.2, 122.0, 115.5, 111.5, 72.4, 31.4, 23.9, 21.5. GC- solvent, H2O (20 mL) was added. The solution was extracted with
MS (EI) m/z = 180 (M)+ for C10H12OS.
CH2Cl2 (3 x 15 mL) and the combined organic extracts were dried
(Na2SO4). The solvent was removed under reduced pressure and the
residue was purified by flash chromatography (Et3N-neutralized
silica gel, hexanes-EtOAc, 20:1, v/v) to afford thiirane 1 in moderate
to good yields.
2-((2-Methylphenyloxy)methyl)thiirane (1d)
Colorless oil, 2.05 g, yield 58%, Rf = 0.46 (Hexanes/EtOAc = 20:1,
v/v). 1H NMR (400 MHz, CDCl3): δ 7.15 (t, J = 7.4 Hz, 2H), 6.89 (dt, J
= 0.8, 7.4 Hz, 1H), 6.80 (d, J = 7.9 Hz, 1H), 4.22 (ddd, J = 10.3, 5.5, 0.8
Hz, 1H), 3.94 (dd, J = 10.4, 6.9 Hz, 1H), 3.33 ‒ 3.27 (m, 1H), 2.61
2-((Naphthalen-1-yloxy)methyl)thiirane (1h)
(ddd, J = 6.2, 1.1, 1.1 Hz, 1H), 2.34 (dd, J = 5.3, 1.4 Hz, 1H), 2.27 (s, Colorless oil, 700 mg, yield 65%, Rf = 0.70 (Hexanes/EtOAc = 20:1,
1
3H). 13C NMR (101 MHz, CDCl3): δ 156.6, 130.8, 127.1, 126.8, 121.0, v/v). H NMR (400 MHz, CDCl3): δ 8.37 ‒ 8.34 (m, 1H), 7.85 ‒ 7.82
111.6, 72.7, 31.6, 23.9, 16.2. GC-MS (EI) m/z = 180 (M)+ for C10H12OS. (m, 1H), 7.54 ‒ 7.47 (m, 3H), 7.38 (t, J = 7.9 Hz, 1H), 6.81 (d, J = 7.6
Hz, 1H), 4.39 (dd, J = 10.2, 5.5 Hz, 1H), 4.12 (dd, J = 10.2, 6.9 Hz, 1H),
2-((4-Methoxyphenoxy)methyl)thiirane (1e)
3.47 ‒ 3.41 (m, 1H), 2.68 (d, J = 6.2 Hz, 1H), 2.43 (dd, J = 5.2, 1.2 Hz,
1H). 13C NMR (101 MHz, CDCl3): δ 154.1, 134.5, 127.4, 126.5, 125.7,
125.6, 125.3, 122.0, 120.8, 105.1, 72.7, 31.4, 23.9. IR (KBr): 2925,
2866, 1595, 1508, 1461, 771, 738 cm-1. GC-MS (EI) m/z = 216 (M)+
for C13H12OS.
White solid, 65 ‒ 66 oC, 2.35 g, yield 60%, Rf = 0.75 (Hexanes/EtOAc
1
= 3:1, v/v). H NMR (400 MHz, CDCl3): δ 6.89 ‒ 6.82 (m, 4H), 4.16
(dd, J = 10.4, 5.6 Hz, 1H), 3.86 (dd, J = 10.0, 6.8 Hz, 1H), 3.77 (s, 3H),
3.28 ‒ 3.22 (m, 1H), 2.59 (d, J = 6.0 Hz, 1H), 2.30 (dd, J = 5.2, 1.2 Hz,
1H). 13C NMR (101 MHz, CDCl3): δ 154.2, 152.5, 115.8, 114.6, 73.4,
55.6, 31.5, 23.9. GC-MS (EI) m/z = 196 (M)+ for C10H12O2S.
2-((Naphthalen-2-yloxy)methyl)thiirane (1i)
White solid. mp 80 ‒ 81 oC. 770 mg, yield 72%, Rf = 0.55
(Hexanes/EtOAc = 20:1, v/v). 1H NMR (400 MHz, CDCl3): δ 7.77 (dd, J
= 8.5, 5.8 Hz, 2H), 7.72 (d, J = 8.2 Hz, 1H), 7.45 (ddd, J = 8.2, 6.8, 1.3
Hz, 1H), 7.36 (ddd, J = 8.1, 6.8, 1.3 Hz, 1H), 7.20 ‒ 7.17 (m, 1H), 7.13
(d, J = 2.5 Hz, 1H). 4.34 (dd, J = 10.1, 5.5 Hz, 1H), 4.03 (dd, J = 10.2,
7.1 Hz, 1H), 3.40 – 3.31 (m, 1H), 2.65 (d, J = 6.2 Hz, 1H), 2.38 (dd, J =
5.2, 1.4 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 156.3, 134.4, 129.6,
129.1, 127.6, 126.8, 126.4, 123.8, 118.7, 107.0, 72.6, 31.3, 24.0. GC-
MS (EI) m/z = 216 (M)+ for C13H12OS.
2-((2,3-Dimethylphenoxy)methyl)thiirane (1f)
Colorless oil, 500 mg, yield 52%, Rf = 0.49 (Hexanes/EtOAc = 3:1,
v/v). 1H NMR (400 MHz, CDCl3): δ 7.04 (t, J = 7.9 Hz, 1H), 6.81 (d, J =
7.5 Hz, 1H), 6.69 (d, J = 8.2 Hz, 1H), 4.20 (dd, J = 10.3, 5.5 Hz, 1H),
3.92 (dd, J = 10.3, 6.9 Hz, 1H), 3.33 ‒ 3.27 (m, 1H), 2.61 (d, J = 6.2 Hz,
1H), 2.33 (dd, J = 5.3, 1.4 Hz, 1H), 2.28 (s, 3H), 2.19 (s, 3H). 13C NMR
(101 MHz, CDCl3): δ 156.4, 138.2, 125.8, 125.6, 122.9, 109.7, 73.1,
31.7, 23.9, 20.1, 11.7. IR (KBr): 2920, 2855, 1584, 1384, 768, 740 cm-
1. GC-MS (EI) m/z = 194 (M)+ for C11H14OS.
2-(((6-Bromonaphthalen-2-yl)oxy)methyl)thiirane (1j)
White solid. mp 95 ‒ 96 oC. 1.22 g, yield 83%, Rf = 0.61
(Hexanes/EtOAc = 20:1, v/v). 1H NMR (400 MHz, CDCl3): δ 7.92 (d, J
= 1.9 Hz, 1H), 7.66 (d, J = 9.0 Hz, 1H), 7.58 (d, J = 8.7 Hz, 1H), 7.50
(dd, J = 8.7, 2.0 Hz, 1H), 7.19 (dd, J = 9.0, 2.5 Hz, 1H), 7.08 (d, J = 2.5
Hz, 1H), 4.31 (dd, J = 10.1, 5.6 Hz, 1H), 4.03 (dd, J = 10.1, 7.0 Hz, 1H),
3.36 ‒ 3.30 (m, 1H), 2.65 (d, J = 6.1 Hz, 1H), 2.37 (dd, J = 5.3, 1.5 Hz,
1H). 13C NMR (101 MHz, CDCl3): δ 156.6, 132.9, 130.2, 129.7, 129.7,
128.7, 128.4, 119.8, 117.3, 106.9, 72.6, 31.2, 23.9. IR (KBr): 2924,
1588, 1498 cm-1. GC-MS (EI) m/z = 294 (M)+ for C13H11BrOS.
2-((2,4-Dimethylphenoxy)methyl)thiirane (1g)
Colorless oil, 250 mg, yield 22%, Rf = 0.39 (Hexanes/EtOAc = 20:1,
v/v). 1H NMR (400 MHz, CDCl3): δ 6.97 (d, J = 2.2 Hz, 1H), 6.93 (d, J =
8.2 Hz, 1H), 6.71 (d, J = 8.2 Hz, 1H), 4.19 (dd, J = 10.3, 5.4 Hz, 1H),
3.90 (dd, J = 10.4, 7.0 Hz, 1H), 3.31 ‒ 3.25 (m, 1H), 2.60 (d, J = 6.2 Hz,
1H), 2.32 (dd, J = 5.3, 1.3 Hz, 1H), 2.26 (s, 3H), 2.23 (s, 3H). 13C NMR
(101 MHz, CDCl3): δ 154.5, 131.6, 130.3, 126.9, 111.9, 73.1, 31.7,
23.9, 20.4, 16.1. IR (KBr): 2920, 2853, 1560, 1503, 1383 cm-1. GC-MS
(EI) m/z = 194 (M)+ for C11H14OS.
2-((4-Chlorophenoxy)methyl)thiirane (1k)
2-Methyl-2-[(3-methylphenoxy)methyl]thiirane (1m)
Colorless oil, 1.89 g, yield 47%, Rf = 0.56 (Hexanes/EtOAc = 10:1,
v/v). 1H NMR (400 MHz, CDCl3): δ 7.15 (d, J = 8.4 Hz, 2H), 6.77 (d, J =
8.4 Hz, 2H), 4.13 (dd, J = 10.8, 2.0 Hz, 1H), 3.82 (dd, J = 10.8, 5.6 Hz,
Colorless oil, 1.02 g, yield 57%, Rf = 0.73 (Hexanes/EtOAc = 10:1,
v/v). 1H NMR (400 MHz, CDCl3): δ 7.16 (t, J = 7.6 Hz, 1H), 6.78 (d, J =
7.2 Hz, 1H), 6.73 ‒ 6.68 (m, 2H), 4.15 (d, J = 9.6 Hz, 1H), 3.86 (d, J =
6 | J. Name., 2012, 00, 1-3
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New Journal of Chemistry
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ARTICLE
1H), 3.28 ‒ 3.24 (m, 1H), 2.82 (t, J = 4.4 Hz, 1H), 2.67 ‒ 2.66 (m, 1H). residue was purified by flash chromatography (Et3N-neutralized
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13C NMR (101 MHz, CDCl3) δ 157.0, 129.3, 126.1, 115.9, 69.0, 50.0, silica gel, hexanes-EtOAc, 20:1, v/v) to afford thiirane 1o in 11%
DOI: 10.1039/C8NJ01117F
44.5. GC-MS (EI) m/z = 200 (M)+ for C9H9ClOS.
yield.
2-((4-Bromophenoxy)methyl)thiirane (1l)
2-Methyl-2-(1-(naphthalen-2-yloxy)ethyl)thiirane (1o)
1
Colorless oil, 407 mg, yield 32%, Rf = 0.66 (Hexanes). H NMR (400 Colorless oil, 133 mg, yield 11%, Rf = 0.76 (Hexanes/EtOAc = 20:1,
1
MHz, CDCl3): δ 7.38 (d, J = 8.8 Hz, 2H), 6.79 (d, J = 8.9 Hz, 2H), 4.15 v/v). H NMR (400 MHz, CDCl3): δ 7.78 ‒ 7.74 (m, 2H), 7.77 (d, J =
(dd, J = 10.2, 5.6 Hz, 1H), 3.89 (dd, J = 10.2, 6.9 Hz, 1H), 3.28 ‒ 3.22 8.0 Hz, 1H), 7.44 (ddd, J = 8.2, 6.9, 1.2 Hz, 1H), 7.35 (ddd, J = 8.1, 6.8,
(m, 1H), 2.61 (d, J = 6.1 Hz, 1H), 2.31 (dd, J = 5.3, 1.4 Hz, 1H). 13C 1.3 Hz, 1H), 7.18 ‒ 7.14 (m, 2H), 4.11 (q, J = 6.4 Hz, 1H), 2.43 (d, J =
NMR (101 MHz, CDCl3) δ 157.5, 132.3, 116.5, 113.4, 72.8, 31.1, 23.8. 1.1 Hz, 1H), 2.34 (d, J = 1.3 Hz, 1H), 1.73 (s, 3H), 1.57 (d, J = 6.4 Hz,
GC-MS (EI) m/z = 244 (M)+ for C9H9BrOS.
3H). 13C NMR (101 MHz, CDCl3): δ 155.5, 134.4, 129.6, 129.2, 127.6,
126.7, 126.4, 123.9, 119.8, 110.0, 82.0, 46.3, 34.9, 20.0, 17.5. IR
(KBr): 2982, 2930, 1629, 1599, 1509, 1377, 1254, 1215 cm-1. GC-MS
(EI) m/z = 244 (M)+ for C15H16OS.
2-Methyl-2-((naphthalen-2-yloxy)methyl)thiirane (1n)
White solid; mp 60 ‒ 61 oC. 863 mg, yield 75%, Rf = 0.71
1
(Hexanes/EtOAc = 20:1, v/v). H NMR (400 MHz, CDCl3): δ 7.79 ‒
General
procedure
for
the
preparation
of
(2,3-
7.75 (m, 2H), 7.72 (d, J = 8.2 Hz, 1H), 7.45 (t, J = 7.5 Hz, 1H), 7.35 (t, J
= 7.5 Hz, 1H), 7.20 (d, J = 8.9 Hz, 1H), 7.11 (s, 1H), 4.29 (d, J = 9.6 Hz,
dihydrobenzo[b][1,4]oxathiin-3-yl)methanols 2
1H), 4.02 (d, J = 9.6 Hz, 1H), 2.56 (d, J = 26.7 Hz, 1H), 1.81 (s, 3H). 13
C
NBS (0.25 mmol) and thiirane 1 (0.25 mmol) were added in DMSO
NMR (101 MHz, CDCl3): δ 156.6, 134.4, 129.5, 129.1, 127.6, 126.7, (5.0 mL) in a 10 mL microwave reaction tube, then the resulting
126.4, 123.8, 118.8, 107.0, 76.1, 42.3, 32.7, 23.5. IR (KBr): 2983, solution was stirred at 110 oC for 15 mins under microwave
2927, 1600, 1510, 1465, 1389 cm-1. GC-MS (EI) m/z = 230 (M)+ for irradiation in a sealed vessel. After cooling water (30 mL) was added,
C14H14OS.
the mixture was extracted with DCM, and the combined extracts
were washed with brine, dried over anhydrous sodium sulfate, and
concentrated in vacuo, the resulting residue was purified by silica
gel column chromatography (200-300 mesh, hexanes-EtOAc, 10:1,
v/v) to afford the product 2.
Synthesis of thiirane 1o9
In a 100 mL round bottom flask, naphthalen-2-ol (7.64 g, 53.0 mmol)
was dissolved in 30 mL of butanone and the mixture was stirred at
room temperature. K2CO3 (11.06 g, 80.0 mmol) and KI (0.83 g, 5.0
mmol) were added to the mixture, followed by addition of 3-chloro-
(2,3-Dihydrobenzo[b][1,4]oxathiin-3-yl)methanol (2a)
2-butanone (5.65 g, 53.0 mmol). The reaction mixture was then Colorless oil, 19 mg, yield 42%, Rf = 0.26 (Hexanes/EtOAc = 3:1, v/v).
maintained under stirring for 12 h. After this time, the precipitate 1H NMR (400 MHz, CDCl3): δ 7.06 ‒ 7.03 (m, 1H), 7.02 ‒ 6.70 (m, 1H),
was removed under filtration and rinsed with ethyl acetate, and the 6.89 ‒ 6.83 (m, 2H), 4.49 (dd, J = 4.2, 11.8 Hz, 1H), 4.33 (dd, J = 2.2,
organic phase was washed with water, and then with saturated 11.7 Hz, 1H), 3.87 (dd, J = 7.4, 11.3 Hz, 1H), 3.85 (dd, J = 6.8, 11.3 Hz,
KOH solution until the complete removal of unreacted naphthalen- 1H), 3.41 (dddd, J = 4.3, 6.8, 2.2, 6.8 Hz, 1H), 1.76 (br s, 1H). 13C
2-ol. The combined organic phases were dried over anhydrous NMR (101 MHz, CDCl3): δ 151.5, 127.5, 125.6, 122.0, 118.4, 116.7,
Na2SO4, concentrated and then dried under vocuum. The resulting 65.7, 62.6, 40.9. IR (KBr): 3440, 2925, 2873, 1477, 1071, 1032 cm-1.
+
product was used in the next step without further purification.
GC-MS (EI) m/z = 182 (M)+ for C9H10O2S. HR-MS (ESI) m/z [M + H]
calcd for C9H11O3S+: 199.0423, found: 199.0426.
In a 50 mL round bottom flask, to a solution of potassium tert-
butoxide (1.68 g, 15.0 mmol) in 10 mL of dimethylsulfoxide was Under ESI condition, benzoxathiine always generates benzoxathiine
added trimethylsulfoxonium iodide (3.63 g, 16.5 mmol) and stirred S-oxide. Thus, the mass spectrum was determined under EI
for 30 min at room temperature. The β-ketoether (3.21 g, 15 mmol) conditions for confirmation of structures.
was added and the resulting solution was stirred overnight. The
(6-Methyl-2,3-dihydrobenzo[b][1,4]oxathiin-3-yl)methanol (2b)
reaction mixture was diluted with EtOAc and water, and the layers
were separated. The aqueous layer was back-extracted with EtOAc.
The combined organic extracts were washed with brine and dried
over Na2SO4. The solvent was removed under reduced pressure.
The resulting product was used in the next step without further
purification.
Colorless oil, 17 mg, yield 35%, Rf = 0.49 (Hexanes/EtOAc = 3:1, v/v).
1H NMR (400 MHz, CDCl3): δ 6.85 (s, 1H), 6.80 (d, J = 8.50, 1H), 6.73
(d, J = 8.50, 1H), 4.46 (dd, J = 4.2, 11.6 Hz, 1H), 4.29 (dd, J = 2.4, 11.3
Hz, 1H), 3.85 (dd, J = 7.6, 11.2 Hz, 1H), 3.84 (dd, J = 6.9, 11.4 Hz, 1H),
3.41 ‒ 3.36 (m, 1H), 2.23 (s, 3H), 1.89 (br s, 1H). 13C NMR (101 MHz,
CDCl3): δ 149.3, 131.5, 127.6, 126.4, 118.1, 116.1, 65.7, 62.6, 40.8,
20.5. IR (KBr): 3403, 2923, 2876, 1601, 1490, 1393, 1065, 1026 cm-1.
GC-MS (EI) m/z = 196 (M)+ for C10H12O2S.
To a stirring solution of oxirane (1.14 g, 5 mmol) in MeOH (20 mL)
was added thiourea (0.76 g, 10 mmol); when it was completely
dissolved, the resulting soln was refluxed for 1.5 h, After removal of
solvent, H2O (20 mL) was added. The solution was extracted with
CH2Cl2 (3 x 15 mL) and the combined organic extracts were dried
(Na2SO4). The solvent was removed under reduced pressure and the
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
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ARTICLE
Journal Name
(7-Methyl-2,3-dihydrobenzo[b][1,4]oxathiin-3-yl)methanol (2ca) 1478, 1377, 1070, 1025 cm-1. GC-MS (EI) m/z = 210 (M)+
View Article Onflioner
DOI: 10.1039/C8NJ01117F
and
(5-methyl-2,3-dihydrobenzo[b][1,4]oxathiin-3-yl)methanol C10H12O3S.
(2cb)
(2,3-Dihydronaphtho[1,2-b][1,4]oxathiin-3-yl)methanol (2h)
Colorless oil, 20 mg, yield 41%, 2ca:2cb
= 1:3, Rf = 0.4
(Hexanes/EtOAc = 3:1, v/v). Major: 1H NMR (400 MHz, CDCl3): δ
6.93 ‒ 6.89 (m, 1H), 6.73 ‒ 6.67 (m, 2H), 4.48 ‒ 4.43 (m, 1H), 4.32 ‒
4.27 (m, 1H), 3.91 ‒ 3.79 (m, 2H), 3.40 ‒ 3.35 (m, 1H), 2.25 (s, 3H).
Minor: 1H NMR (400 MHz, CDCl3): δ 6.93 ‒ 6.89 (m, 1H), 6.78 (d, J =
7.6 Hz, 1H), 6.73 ‒ 6.67 (m, 1H), 4.48 ‒ 4.43 (m, 1H), 4.32 ‒ 4.27 (m,
1H), 3.91 ‒ 3.79 (m, 2H), 3.47 ‒ 3.42 (m, 1H), 2.23 (s, 3H). 13C NMR
(101 MHz, CDCl3): δ 151.2, 135.8, 135.7, 134.0, 127.3, 124.6, 123.2,
123.0, 118.9, 118.5, 115.8, 112.8, 65.8, 65.2, 62.7, 62.5, 40.8, 40.7,
20.8, 19.4. IR (KBr): 3389, 2925, 2878, 1566, 1488, 1066, 1026 cm-1.
GC-MS (EI) m/z = 196 (M)+ for C10H12O2S.
Colorless oil, 34 mg, yield 59%, Rf = 0.25 (Hexanes/EtOAc = 3:1, v/v).
1H NMR (400 MHz, CDCl3): δ 8.10 (d, J = 8.2 Hz, 1H), 7.72 (d, J = 7.9
Hz, 1H), 7.48 ‒ 7.36 (m, 3H), 7.09 (d, J = 8.6 Hz, 1H), 4.72 (dd, J = 3.8,
11.8 Hz, 1H), 4.49 (d, J = 11.8 Hz, 1H), 3.95 (dd, J = 8.1, 11.3 Hz, 1H),
3.89 (dd, J = 7.0, 11.2 Hz, 1H), 3.56 ‒ 3.51 (m, 1H), 1.93 (br s, 1H).
13C NMR (101 MHz, CDCl3): δ 146.2, 132.1, 127.6, 126.0, 125.9,
125.5, 125.4, 121.4, 120.6, 110.6, 65.9, 62.6, 41.0. IR (KBr): 3381,
2927, 2879, 1622, 1588, 1397, 1050, 1023 cm-1. GC-MS (EI) m/z =
232 (M)+ for C13H12O2S.
(2,3-Dihydronaphtho[2,1-b][1,4]oxathiin-2-yl)methanol (2i)
(8-Methyl-2,3-dihydrobenzo[b][1,4]oxathiin-3-yl)methanol (2d)
Colorless oil, 34 mg, yield 59%, Rf = 0.25 (Hexanes/EtOAc = 3:1, v/v).
1H NMR (400 MHz, CDCl3): δ 7.87 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 8.1
Hz, 1H), 7.52 (d, J = 9.2 Hz, 1H), 7.51 (ddd, J = 8.4, 6.9, 1.3 Hz, 1H),
7.39 (ddd, J = 8.0, 6.9, 1.1 Hz, 1H), 7.05 (d, J = 8.9 Hz, 1H), 4.60 (dd, J
= 11.5, 4.2 Hz, 1H), 4.45 (dd, J = 11.5, 2.2 Hz, 1H), 3.97 ‒ 3.87 (m,
2H), 3.57 (dddd, J = 2.3, 4.2, 6.8, 6.8 Hz, 1H), 2.02 (dd, J = 7.0, 5.3 Hz,
1H). 13C NMR (101 MHz, CDCl3): δ 149.1, 131.2, 129.6, 128.4, 126.4,
125.8, 124.3, 122.1, 119.6, 109.44, 65.6, 62.5, 40.3. IR (KBr): 3423,
2964, 2926, 1619, 1567, 1051, 1026 cm-1. GC-MS (EI) m/z = 232 (M)+
for C13H12O2S.
Colorless oil, 13 mg, yield 27%, Rf = 0.44 (Hexanes/EtOAc = 3:1, v/v).
1H NMR (400 MHz, CDCl3): δ 6.91 ‒ 6.86 (m, 2H), 6.77 (t, J = 7.4 Hz,
1H), 4.52 (dd, J = 11.6, 4.3 Hz, 1H), 4.34 (dd, J = 11.6, 2.3 Hz, 1H),
3.92 ‒ 3.80 (m, 2H), 3.41 (dddd, J = 4.3, 6.8, 2.3, 6.8 Hz, 1H), 2.18 (s,
3H), 1.95 (dd, J = 7.1, 5.3 Hz, 1H). 13C NMR (101 MHz, CDCl3): 143.4,
127.7, 127.1, 125.1, 121.3, 65.8, 62.7, 41.1, 16.2. IR (KBr): 3372,
2925, 1587, 1378, 1067, 1025 cm-1. GC-MS (EI) m/z = 196 (M)+ for
C10H12O2S.
(6-Methoxy-2,3-dihydrobenzo[b][1,4]oxathiin-3-yl)methanol (2e)
(8-Bromo-2,3-dihydronaphtho[2,1-b][1,4]oxathiin-2-yl)methanol
Colorless oil, 8 mg, yield 15%, Rf = 0.27 (Hexanes/EtOAc = 3:1, v/v). (2j)
1H NMR (400 MHz, CDCl3): δ 6.77 (d, J = 8.8 Hz, 1H), 6.58 ‒ 6.56 (m,
2H), 4.45 (dd, J = 4.0, 11.6 Hz, 1H), 4.26 (d, J = 11.6 Hz, 1H), 3.89 (dd,
J = 7.7, 11.7 Hz, 1H), 3.84 (dd, J = 6.9, 11.5 Hz, 1H), 3.73 (s, 3H), 3.42
‒ 3.37 (m, 1H), 1.85 (br s, 1H). 13C NMR (101 MHz, CDCl3): δ 154.3,
145.6, 119.0, 117.3, 112.1, 111.5, 65.7, 62.7, 55.7, 41.0. IR (KBr):
3432, 2928, 1602, 1508, 1062, 1032 cm-1. GC-MS (EI) m/z = 212 (M)+
for C10H12O3S.
Colorless oil, 34 mg, yield 44%, Rf = 0.28 (Hexanes/EtOAc = 3:1, v/v).
1H NMR (400 MHz, CDCl3): δ 7.90 (d, J = 2.0 Hz, 1H), 7.73 (d, J = 9.0
Hz, 1H), 7.55 (dd, J = 9.0, 2.0 Hz, 1H), 7.42 (d, J = 8.9 Hz, 1H), 7.06 (d,
J = 8.9 Hz, 1H), 4.59 (dd, J = 11.5, 4.2 Hz, 1H), 4.44 (dd, J = 11.5, 2.2
Hz, 1H), 3.93 (dd, J = 10.3, 6.5 Hz, 1H), 3.89 (dd, J = 10.3, 5.9 Hz, 1H),
3.56 (dddd, J = 2.1, 4.2, 6.8, 6.8 Hz, 1H), 2.00 (br s, 1H). 13C NMR
(101 MHz, CDCl3): δ 149.3, 130. 8, 130.3, 129.8, 129.6, 124.8, 124.0,
(7,8-Dimethyl-2,3-dihydrobenzo[b][1,4]oxathiin-3-yl)methanol (2f) 120.7, 118.0, 110.0, 65.6, 62.5, 40.2. IR (KBr): 3431, 2926, 2877,
1588, 1390, 1074, 500 cm-1. GC-MS (EI) m/z = 310 (M)+ for
Colorless oil, 35 mg, yield 66%, Rf = 0.39 (Hexanes/EtOAc = 3:1, v/v).
1H NMR (400 MHz, CDCl3): δ 6.80 (d, J = 7.9 Hz, 1H), 6.69 (d, J = 7.9
C13H11BrO2S.
Hz, 1H), 4.51 (dd, J = 4.3, 11.6 Hz, 1H), 4.31 (d, J = 2.0, 11.8 Hz, 1H), (3,7-Dimethyl-2,3-dihydrobenzo[b][1,4]oxathiin-3-yl)methanol
3.91 ‒ 3.79 (m, 2H), 3.40 (dddd, J = 4.2, 2.3, 6.8, 6.8 Hz, 1H), 2.21 (s, (2ma) and (3,5-dimethyl-2,3-dihydrobenzo[b][1,4]oxathiin-3-
3H), 2.11 (s, 3H), 1.95 (dd, J = 5.4, 7.4 Hz, 1H). 13C NMR (101 MHz, yl)methanol (2mb)
CDCl3): δ 134.3, 126.2, 124.0, 123.1, 113.2, 105.0, 69.6, 67.3, 40.9,
19.8, 11.7. IR (KBr): 3450, 2925, 1655, 1384, 1075, 1032 cm-1. GC-
Colorless oil,
6 mg, yield 12%, 2ma:2mb = 1:2, Rf = 0.66
(Hexanes/EtOAc = 3:1, v/v). Major: 1H NMR (400 MHz, CDCl3): δ
7.94 ‒ 6.89 (m, 1H), 6.79 ‒ 6.69 (m, 2H), 4.34 (d, J = 11.6 Hz, 1H),
MS (EI) m/z = 210 (M)+ for C10H12O3S.
(6,8-Dimethyl-2,3-dihydrobenzo[b][1,4]oxathiin-3-yl)methanol (2g) 3.94 (d, J = 11.6 Hz, 1H), 3.77 ‒ 3.71 (m, 1H), 3.66 ‒ 3.62 (m, 1H),
1
2.26 (s, 3H). 1.83 (br s, 1H), 1.37 (s, 3H). Minor: H NMR (400 MHz,
Colorless oil, 23 mg, yield 43%, Rf = 0.43 (Hexanes/EtOAc = 3:1, v/v).
1H NMR (400 MHz, CDCl3): δ 6.70 (s, 1H), 6.68 (s, 1H), 4.49 (dd, J =
4.2, 11.6 Hz, 1H), 4.30 (d, J = 2.3, 11.6 Hz, 1H), 3.91 ‒ 3.79 (m, 2H),
3.39 (dddd, J = 4.2, 2.3, 6.9, 6.9 Hz, 1H), 2.19 (s, 3H), 2.15 (s, 3H),
1.93 (dd, J = 5.3, 7.2 Hz, 1H). 13C NMR (101 MHz, CDCl3): δ 130.7,
128.0, 125.0, 122.4, 65.8, 62.7, 41.1, 20.4, 16.1. IR (KBr): 3366, 2922,
CDCl3): δ 7.94 ‒ 6.89 (m, 1H), 6.79 ‒ 6.69 (m, 2H), 3.94 (d, J = 11.5
Hz, 1H), 3.91 (d, J= 11.6 Hz, 1H), 3.77 ‒ 3.71 (m, 1H), 3.66 ‒ 3.62 (m,
1H), 2.22 (s, 3H), 1.83 (br s, 1H), 1.41 (s, 3H). 13C NMR (101 MHz,
CDCl3) δ 127.0, 124.6, 123.2, 123.0, 118.7, 115.6, 71.0, 70.4, 66.8,
66.6, 47.2, 45.0, 20.9, 19.5. IR (KBr): 3434, 2925, 1608, 1379, 1052,
1029 cm-1. GC-MS (EI) m/z = 210 (M)+ for C11H14O2S.
8 | J. Name., 2012, 00, 1-3
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New Journal of Chemistry
Journal Name
ARTICLE
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J. J. Tegeler, H. H. Ong and J. A. Profitt, J. Heterocycl.
(3-Methyl-2,3-dihydronaphtho[2,1-b][1,4]oxathiin-2-yl)methanol
(2n)
View Article Online
Chem. 1983, 20, 867.
DOI: 10.1039/C8NJ01117F
A. Arnoldi, A. Bassoli, R. Caputo, L. Merlini, G. Palumbo
and S. Pedatella, J. Chem. Soc. Perkin Trans 1994, 1241.
(a) W. Xu and J. X. Xu, Curr. Org. Synth. 2016, 13, 73. (b)
J. X. Xu, Synthesis of Four- to Seven-Membered
Heterocycles by Ring Expansion: Ring Expansions of
Thiiranes and Thietanes. In M. D’hooghe and H. J. Ha
Eds. Synthesis of 4-to 7-membered Heterocycles by
Ring Expansion. Top. Heterocycl. Chem., 2016, 41, 311-
362. Springer, Switzerland.
(a) C. Zhou and J. X. Xu, Prog. Chem. 2012, 24, 238. (b)
H. Yu, S. L. Cao, L. L. Zhang, G. Liu and J. X. Xu, Synthesis
2009, (13), 2205. (c) X. Y. Li and J. X. Xu, Tetrahedron
2011, 67, 1681. (d) J. Dong and J. X. Xu, Org. Biomol.
Chem. 2017, 15, 836. (e) X. P. Chen and J. X. Xu,
Tetrahedron Lett. 2017, 58, 1651. (f) J. X. Huang, F.
Wang, D. M. Du and J. X. Xu, Synthesis 2005, (13), 2122.
(g) J. X. Huang, D. M. Du and J. X. Xu, Synthesis 2006,
(2), 315.
Golden yellow oil, 21 mg, yield 45%, Rf = 0.53 (Hexanes/EtOAc = 3:1,
v/v). 1H NMR (400 MHz, CDCl3): δ 7.77 (d, J = 8.3 Hz, 1H), 7.68 (d, J =
8.1 Hz, 1H), 7.45 (d, J = 8.7 Hz, 1H), 7.42 (ddd, J = 1.4, 6.7, 8.2 Hz,
1H), 7.31 (ddd, J = 1.1, 6.9, 8.0 Hz, 1H), 7.00 (d, J = 9.1 Hz, 1H), 4.39
(d, J = 11.4 Hz, 1H), 3.98 (d, J = 11.4 Hz, 1H), 3.71 (d, J = 11.5 Hz, 1H),
3.62 (d, J = 11.3 Hz, 1H), 1.87 (br s, 1H), 1.41 (s, 3H). 13C NMR (101
MHz, CDCl3): δ 148.1, 131.0, 128.4, 126.4, 125.7, 124.2, 122.2, 119.3,
110.4, 105.0, 70.8, 66.5, 44.6, 21.0. IR (KBr): 3437, 2926, 2877, 1618,
1502, 1228, 1074, 1022 cm-1. GC-MS (EI) m/z = 246 (M)+ for
C14H14O2S.
8
9
(2,3-Dimethyl-2,3-dihydronaphtho[2,3-b][1,4]oxathiin-3-
yl)methanol (2o)
Grass green oil, 20 mg, yield 31%, Rf = 0.57 (Hexanes/EtOAc = 3:1,
v/v). 1H NMR (400 MHz, CDCl3): δ 7.87 (d, J = 8.4 Hz, 1H), 7.75 (d, J =
8.1 Hz, 1H), 7.53 (d, J = 9.1 Hz, 1H), 7.50 (ddd, J = 1.3, 7.0, 8.2 Hz,
1H), 7.38 (ddd, J = 1.0, 6.9, 8.0 Hz, 1H), 7.06 (d, J = 8.9 Hz, 1H), 4.43
(q, J = 6.6 Hz, 1H), 3.83 (d, J = 10.8 Hz, 1H), 3.74 ‒ 3.69 (m, 1H), 1.95
(d, J = 6.9 Hz, 1H), 1.51 (s, 3H), 1.50 (d, J = 6.6 Hz, 3H). 13C NMR (101
MHz, CDCl3): δ 148.8, 131.0, 129.5, 128.4, 126.4, 125.9, 124.1, 122.4,
119.4, 110.4, 77.9, 64.3, 49.2, 22.1, 15.9. IR (KBr): 3429, 1596, 1460,
1384, 1234 cm-1. GC-MS (EI) m/z = 260 (M)+ for C15H16O2S.
(a) D. R. M. Moreira, A. D. T. de Oliveira, P. A. T. de
Moraes Gomes, C. A. de Simone, F. S. Villela, R. S.
Ferreira, A. C. da Silva, T. A. R. dos Santos, M. C. A. B.
de Castro, V. R. A. Pereira and A. C. L. Leite, Eur. J. Med.
Chem. 2014, 75, 467. (b) C. Molinaro, A.-A. Guilbault
and B. Kosjek, Org. Lett. 2010, 12, 3772.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (Nos. 21572017 and 21772010).
Notes and references
1
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(a) M. Muehlstaedt, N. Stransky, A. Seifert, E.
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