Efficient synthesis of 2-alkylidene-4h-3,1-benzoxathiin-4-ones and determination of their double bond configuration

Article abstract of DOI:10.3987/COM-14-12943

2-Alkylidene-4H-3,1-benzoxathiin-4-ones were efficiently synthesized by reaction of 2-(acylthio)benzoic acids with condensation reagents in the presence of base. The E and Z isomers of the products were distinguished by comparison of the chemical shifts o

Full text of DOI:10.3987/COM-14-12943

HETEROCYCLES, Vol. 89, No. 4, 2014
981
HETEROCYCLES, Vol. 89, No. 4, 2014, pp. 981 - 993. © 2014 The Japan Institute of Heterocyclic Chemistry
Received, 15th January, 2014, Accepted, 18th February, 2014, Published online, 21st February, 2014
DOI: 10.3987/COM-14-12943
EFFICIENT SYNTHESIS OF 2-ALKYLIDENE-4H-3,1-BENZOXATHIIN-
4-ONES AND DETERMINATION OF THEIR DOUBLE BOND
CONFIGURATION
Masao Shimizu,*,a Masaki Yamanaka,b Wataru Ando,a Shigeru Shimada,a
Takeo Konakahara,b and Norio Sakaib
aNational Institute of Advanced Industrial Science and Technology (AIST), 1-1-1
Higashi, Tsukuba, Ibaraki 305-8565, Japan; E-mail: m.shimizu@aist.go.jp
bDepartment of Industrial Chemistry, Faculty of Science and Technology, Tokyo
University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan
Abstract – 2-Alkylidene-4H-3,1-benzoxathiin-4-ones were efficiently synthesized
by reaction of 2-(acylthio)benzoic acids with condensation reagents in the presence
of base. The E and Z isomers of the products were distinguished by comparison of
1
the chemical shifts of the vinylic protons in the H NMR spectra of the
4H-3,1-benzoxathiin-4-ones and their corresponding 1-oxides.
INTRODUCTION
4H-3,1-Benzoxathiin-4-ones have been reported to have insecticidal and fungicidal activities,1,2 and
various 4H-3,1-benzoxathiin-4-ones have been patented for use as crop protection agents.3 However, the
reactivity of 4H-3,1-benzoxathiin-4-ones has not been extensively investigated: ring-opening reactions
with nucleophiles,4-7 oxidation reactions,6,8 sulfurization reactions,4,5 photoreactions,8 and thermolysis9 are
the only reactions to have been reported. In a previous paper, we reported the synthesis of
1,2-benzisothiazolin-3(2H)-ones by ring transformation of 4H-3,1-benzoxathiin-4-one 1-oxides with
amines,10 and 4H-3,1-benzoxathiin-4-ones are increasingly being used as starting materials.
4H-3,1-Benzoxathiin-4-ones are usually synthesized by the reaction of thiosalicylic acids with carbonyl
compounds or their acetals.2,6,11 The use of acetylene compounds instead of carbonyl compounds has
recently been reported,12 and various 2-monosubstituted and 2,2-disubstituted 4H-3,1-benzoxathiin-4-one
derivatives were synthesized in this way. However, the synthesis of 2-functionalized group substituted
4H-3,1-benzoxathiin-4-ones, such as 2-alkoxy-13 and 2-alkylamino-derivatives,14 has rarely been reported.

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HETEROCYCLES, Vol. 89, No. 4, 2014
In contrast, the chemistry of 4H-1,3-benzodioxin-4-ones, which are oxo analogs of
4H-3,1-benzoxathiin-4-ones, has been thoroughly investigated, and 2-alkoxy-4H-1,3-benzodioxin-4-ones
are of interest as prodrugs of acylsalicylic acids.15 The synthesis of 2-methylene-4H-1,3-benzodioxin-4-one
as a key intermediate for 2-alkoxy-4H-1,3-benzodioxin-4-one derivatives has been reported,16 but this
2-methylene-substituted compound was obtained unexpectedly from the reaction of 2-acetoxybenzoyl
chloride and triethylamine; the authors had intended to synthesize isoflavone derivatives.
2-Methylene-4H-3,1-benzoxathiin-4-one was also reported to be formed, in low yield, as an unexpected
product of the reaction of 2-(acetylthio)benzoic acid with amines in the presence of a condensation reagent;
the intended products were 2-(acetylthio)benzamides.17 However, no characterization data for this
unexpected byproduct were presented in the report.
As
a
part of our research on 4H-3,1-benzoxathiin-4-ones, we are interested in
2-alkylidene-4H-3,1-benzoxathiin-4-one chemistry. In this paper, we present a simple method for the
synthesis of 2-alkylidene-4H-3,1-benzoxathiin-4-ones, and we also describe the determination of their
double bond configuration.
RESULTS AND DISCUSSION
On
the
basis
of
the
previously
reported
method
for
the
synthesis
of
2-alkylidene-4H-3,1-benzodioxin-4-ones,16 we attempted to cyclize 2-(acylthio)benzoyl chlorides in the
presence of base. Thiosalicylic acid (1) was converted to its S-acetyl derivative (2a) by reaction with acetyl
chloride in THF, and 2a was allowed to react with thionyl chloride in refluxing toluene to afford
2-(acetylthio)benzoyl chloride (3). Although 2-methylene-4H-3,1-benzodioxin-4-one was previously
synthesized under severe reaction conditions (e.g., reaction for 15 h at 110 °C in toluene), we were able to
synthesize 2-methylene-4H-3,1-benzoxathiin-4-one (4a) under mild conditions, refluxing dichloromethane
for 3 h, in 72% yield (Scheme 1). The structure of the product was confirmed by observation of the two
vinylic proton peaks in the NMR spectrum.
O
COCl
SAc
CO2H
SAc
CO2H
SH
Et3N
SOCl2
AcCl / Et3N
THF
O
CH2Cl2
toluene
S

100 C, 3 h

0 C, 1 h
reflux, 3 h
3
4a
2a
1
Scheme 1. Synthesis of 2-methylene-4H-3,1-benzoxathiin-4-one 4a from acid chloride 3

HETEROCYCLES, Vol. 89, No. 4, 2014
983
Next, we investigated the one-step synthesis of 2-alkylidene-4H-3,1-benzoxathiin-4-ones 4 from
2-(acylthio)benzoic acids 2 by using condensation reagents. In the literature,17 the use of
O-benzotriazole-N,N,N,N-tetramethyluronium hexafluorophosphate as a condensation reagent for the
synthesis 4a has been reported. We investigated three commercially available condensation reagents:
Table 1. Cyclization of 2-(acylthio)benzoic acid (2) with condensation reagentsa)
O
CO2H
Condensation reagent
O
O
Et3N
R
S
CHR2
S
CH2Cl2, reflux
R
4
2
Condensation
2
Time / h
Entry
R
Product
Yieldc) /%
reagentb)
MR
4a
4b
4a
4b
4a
4b
5
1
7
3
8
3
41
86
80
94
13
90
2a
H
Ph
H
1
2
3
4
5
6
2b
2a
2b
2a
2b
MR
DMC
DMC
Ph
H
DMT-MM
DMT-MM
Ph
a) 2, 1.5 mmol; condensation reagent, 2.0 mmol; Et3N, 7.5 mmol; CH2Cl2, 20 mL.
b)
Cl
MeO
N
Me
N
N
Me
Me
N
Me
Cl
I-
N
N
N
O
Cl
Cl
MeO
DMC
MR
DMT-MM
c) Isolated product.
2-chloro-1-methylpyridinium iodide (Mukaiyama reagent),18 2-chloro-1,3-dimethylimidazolinium
chloride (DMC),19 and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride20 (Table 1).
Cyclization of 2-(acylthio)benzoic acids 2 proceeded with these condensation reagents in the presence of
base, and 2-methylene-4H-3,1-benzoxathiin-4-ones 4 were obtained. Although the three condensation
reagents gave similar yields in the cyclization of 2-(diphenylacetylthio)benzoic acid (2b), DMC gave a
substantially higher yield than the other condensation reagents in the cyclization of 2-(acetylthio)benzoic
acid (2a). Therefore, we used DMC as a condensation reagent to investigate the cyclization of various
substituted 2-(acylthio)benzoic acids
2
(Table 2). Monophenyl derivatives 2d–f gave
2-benzylidene-4H-3,1-benzoxathiin-4-ones 4d–f in good yields as single isomers (>99:1, entries 4–6).

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HETEROCYCLES, Vol. 89, No. 4, 2014
Reactions of 2-(acylthio)benzoic acids with ether substituents resulted in mixtures of E and Z isomers,
which were separated by silica gel column chromatography (entries 7–9). 2-(Propionylthio)benzoic acid
(2j) gave a 1:1 mixture of the product isomers (entry 10). Under these reaction conditions, the treatment of
2-(isobutyrylthio)benzoic acid (2c) with DMC afforded 4c in 56% yield, but further investigation revealed
that 4c could be synthesized in 88% yield if pyridine was used as a base in 1,2-dichloroethane at 80 °C
(entry 3).
Table 2. Synthesis of 2-alkylidene-4H-3,1-benzoxathiin-4-one 4a)
O
CO2H
DMCb)
O
O
R1
R1
Et3N
CH2Cl2, reflux
S
S
R2
R2
2
4
c) Ratio of isomersd)
Time
/ h
Yield
/%
Entry
2
R1
R2
Product
(E : Z)
2a
2b
2c
2d
2e
4a
4b
4c
4d
4e
4f
4g
4h
4i
H
Ph
Me
Ph
1
2
H
Ph
Me
H
H
H
H
H
H
H
7
3
5
5
3
5
5
7
5
5
80
94
88
88
91
85
89
82
81
77
-
-
-
3e)
4
>99 : 1
>99 : 1
>99 : 1
77 : 23
72 : 28
77 : 23
50 : 50
4-ClC6H4
5
6
7
8
9
10
2f 4-MeOC6H4
2g
2h
2i
PhO
MeO
AcO
Me
2j
4j
a) 2, 1.5 mmol; DMC, 2.0 mmol; Et3N, 7.5 mmol; CH2Cl2, 20 mL.
b) DMC: 2-chloro-1,3-dimethylimidazolinium chloride.
c) Isolated product.
d) Determined with 1H-NMR. See Table 3.
e) 1,2-Dichloroethane (20 mL); 80 °C; pyridine (7.5 mmol).
A single crystal of the major isomer of 2-(phenoxymethylene)-4H-3,1-benzoxathiin-4-one (4g) was
obtained, and the E configuration was confirmed by X-ray crystallography (Figure 1). However, the double
bond configurations of the other products still had to be determined. The 1H NMR chemical shifts of the E
and Z isomers of methyl styryl sulfide and methyl styryl sulfoxide have been measured,21 and the oxidation
reaction was found to shift the protons  to the sulfur atoms to lower field; the change in chemical shift for
the E isomer ( = 0.59 ppm) is larger than that for the Z isomer ( = 0.26 ppm). We used these results to
determine the double bond structures of 2-alkylidene-4H-3,1-benzoxathiin-4-ones 4.
2-(Phenoxymethylene)-4H-3,1-benzoxathiin-4-one (4g), the structure of which had been determined by
X-ray crystallography, was oxidized with m-chloroperoxybenzoic acid (mCPBA) in dichloromethane to
afford the corresponding 1-oxide (5g) in 79% yield. The oxidation shifted the vinylic proton signal

HETEROCYCLES, Vol. 89, No. 4, 2014
985
downfield by 0.56 ppm. In contrast, oxidation of 4g, a minor product of the cyclization, with mCPBA gave
sulfoxide 5g in 76% yield, and the signal for the vinylic proton in the oxidized compound was
Figure 1. ORTEP drawing of 4g (showing thermal ellipsoids at the 50% probability level).
Table 3. Oxidation of 4H-3,1-benzoxathiin-4-onesa) and chemical shifts of vinylic protons
O
O
CPBA
m
O
O
O
O
R
H
R
H
CH2Cl2
major
minor
S
O
O
S
4
CO2H
O
H
R
DMC
H
5
R
O
S
H
CPBA
m
2
CH2Cl2
S
S
O
R
5'
4'
1H-NMR chemical shift
Yieldb)
(%)
85 c)
70 c)
88 c)
79
76
67
61
62
Entry
R
Product
4
Conformation

5 or 5'
4 or 4'
6.09
6.04
6.05
6.51
7.12
6.02
6.72
7.17
7.70
Ph
4-ClC6H4
4-MeOC6H4
PhO
E
E
6.67 0.58
6.62 0.58
6.61 0.56
7.07 0.56
7.37 0.25
6.60 0.58
6.97 0.25
7.72 0.55
7.93 0.23
4d
4e
4f
4g
4'g
4h
4'h
4i
5d
5e
5f
5g
5'g
5h
5'h
5i
1
2
3
4
5
6
7
8
9
E
E d)
Z
PhO
MeO
MeO
AcO
E
Z
E
Z
AcO
64
4'i
5'i
4
a) : 1.0 mmol, CPBA: 1.1 mmol, CH Cl : 10 mL, rt, 30 min.
m
2
2
b) Isolated product.
c) Calculated from 1H-NMR spectra.
d) Determined with X-ray crystallographic analysis (see Figure 1).

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HETEROCYCLES, Vol. 89, No. 4, 2014
shifted 0.25 ppm downfield. That is, the oxidation-induced downfield shift of the vinylic proton of the E
isomer was larger than that of the Z isomer. This result was in good agreement with the results reported for
methyl styryl sulfide and confirmed that the double bond configurations of the
1
2-alkylidene-4H-3,1-benzoxathiin-4-ones could be determined by comparison of their H NMR spectra
before and after oxidation.
Isolated isomers of 2-alkylidene-4H-3,1-benzoxathiin-4-ones 4 and 4 were oxidized with mCPBA (Table
3). All the major isolated isomers showed behavior consistent with the E configuration; that is, the vinylic
protons shifted downfield by approximately 0.58 ppm after oxidation. In contrast, the vinylic protons of the
minor isomers shifted downfield by approximately 0.24 ppm, indicating that they were Z isomers. Although
a single isomer was obtained from monophenyl derivatives 3d–f under these reaction conditions, the
oxidation results clearly indicated that the E isomers formed predominantly. Even when the isomers were
not separable, the 1H NMR peaks could be assigned by oxidation of the mixture (entry 10).
Plausible reaction mechanisms for the formation of 2-alkylidene-4H-3,1-benzoxathiin-4-ones are depicted
in Scheme 2. In the first step, 1 equivalent amount of triethylamine deprotonates the carboxylic acid and the
resulting anion reacts with the condensation reagent. Then the functional group derived from the
condensation reagent could be eliminated by attack of the oxygen atom of the acyl carbonyl group on the
ester carbonyl group, facilitated by electron donation from the sulfur atom. The result would be a
benzoxathiinium cation, which could undergo elimination of a proton with triethylamine (Route A). Steric
repulsion between the sulfur and oxygen atoms was unlikely to be sufficient to control the double bond
configuration. As a result, products were obtained as E/Z mixtures. On the centrally, in the case that the R
substituents are aryl groups, it is possible that benzene and imidazolinium rings can interact each other, and
that the intermediate becomes somewhat stable. Therefore, triethylamine attacks the -proton from less
hindered side and the oxygen atom of the thioester carbonyl group continuously attacks to the ester
carbonyl group, which results in predominant formation of E-alkylidene products (Route B).
In conclusion, we synthesized 2-alkylidene-4H-3,1-benzoxathiin-4-ones by means of the reactions of
2-acylthiosalicylic acids with condensation reagents. When double bond isomers were possible, the E
isomers predominated, and the double bond configurations were determined by comparison of the vinylic
proton chemical shifts with those of the corresponding 1-oxide derivatives.

HETEROCYCLES, Vol. 89, No. 4, 2014
987
Me
O
N
Me
Me
N
N
O
S
O
S
O
S
N
O
Me
Et3N
O
O
O
R
R
H
R
Route A
O
H
H
H
H
O
S
DMC
Et3N
OH
Me
Me
O
N
Me
N
N
O
O
S
N
O
R
2
H
Me
H
O
O
R
R
Route B
S
(R = aryl)
H
H
H
Et3N
Scheme 2. Plausible mechanisms for formation of 2-alkylidene-4H-3,1-benzoxathiin-4-ones
EXPERIMENTAL
Melting points were determined on a Mettler FP90 microscopic plate and are uncorrected. 1H NMR spectra
were obtained with a JEOL JNM-ECX400 spectrometer operating at 400 MHz, and chemical shifts (δ) are
reported in ppm relative to internal tetramethylsilane. 13C NMR spectra were obtained with a JEOL
JNM-ECX400 spectrometer operating at 100 MHz, and chemical shifts (δ) are reported in ppm relative to
internal tetramethylsilane. IR spectra were recorded on a JASCO FT IR-4100 spectrophotometer.
Elemental analysis and high-resolution mass spectral analysis were performed by the Analytical Center at
the National Institute of Advanced Industrial Science and Technology. An X-ray structure was measured
with a Bruker AXS APEX2 diffractometer.
General procedure for synthesis of 2-(acylthio)benzoic acids 2. To a solution of thiosalicylic acid (1,
5.0 mmol, 771 mg) in THF (20 mL) cooled on an ice bath were added an acyl chloride (1.1 mmol) and
triethylamine (7.5 mmol, 759 mg). The mixture was stirred for 1 h under a nitrogen atmosphere at 0 °C, and
then the solvent was evaporated under reduced pressure. The reaction mixture was dissolved in water, and
diluted HCl (5 mL) was added. The crude product was extracted with AcOEt, and the organic layer was
dried over MgSO4. The solvent was evaporated under reduced pressure, and purification of the crude
product by recrystallization from AcOEt–hexane afforded 2.
Synthesis
of
2-methylene-4H-3,1-benzoxathiin-4-one
(4a)
from
acid
chloride
3.
2-(Acetylthio)benzoic acid (2a, 5.0 mmol, 980 mg) was dissolved in toluene (50 mL), and thionyl chloride
(1 mL) was added to the solution. The reaction mixture was heated to 100 °C for 3 h. After the reaction, the
solvent was evaporated to give 2-(acetylthio)benzoyl chloride (3). To a solution of 3 (2 mmol, 429 mg) in

988
HETEROCYCLES, Vol. 89, No. 4, 2014
CH2Cl2 (30 mL) was added triethylamine (6.0 mmol, 607 mg), and the mixture was stirred at reflux for 3 h.
The solvent was evaporated under reduced pressure, and the crude product was purified by silica gel
column chromatography (eluent 4 : 1 CH2Cl2 : hexane) to afford 4a in 72% yield.
2-Methylene-4H-3,1-benzoxathiin-4-one (4a): mp 51.3-53.0 °C (AcOEt-hexane); Rf (CH2Cl2 : hexane =
4 : 1) 0.6; 1H-NMR (400 MHz, CDCl3) δ 4.92 (1H, d, J = 2.4 Hz), 5.19 (1H, d, J = 2.4 Hz), 7.21 (1H, d, J =
7.6 Hz), 7.29 (1H, td, J = 7.6, 1.2 Hz), 7.51 (1H, td, J = 7.6, 1.2 Hz), 8.15 (1H, dd, J = 7.6, 1.2 Hz);
13C-NMR (100 MHz, CDCl3) δ 102.2, 121.9, 125.5, 126.6, 132.5, 134.5, 136.2, 145.0, 160.5; IR (KBr) max
3029, 1747, 1616, 1440, 1283, 1099, 853 cm-1. Anal. Calcd for C9H6O2S: C 60.66; H 3.39. Found: C 60.69;
H 3.31.
General procedure for the synthesis of 4 with condensation reagents. To a solution of 2 (1.5 mmol) in
CH2Cl2 (20 mL) were added a condensation reagent (2.0 mmol) and triethylamine (7.5 mmol, 759 mg), and
the mixture was stirred at reflux for 3–8 h. After water was added to the reaction mixture, the products were
extracted with CH2Cl2. The organic layer was washed with water and dried over MgSO4. The solvent was
evaporated under reduced pressure, and the crude product was purified by silica gel column
chromatography with an appropriate solvent.
2-Diphenylmethylene-4H-3,1-benzoxathiin-4-one (4b): mp 165-166 °C (AcOEt-hexane); Rf (CH2Cl2 :
hexane = 2 :1) 0.5; 1H-NMR (400 MHz, CDCl3) δ 7.13 (1H, d, J = 7.6 Hz), 7.22-7.48 (12H, m), 8.18-8.21
(1H, m); 13C-NMR (100 MHz, CDCl3): 121.7, 125.5, 126.4, 127.8, 128.1, 128.3, 128.5, 129.9, 130.1, 130.3,
132.4, 134.4, 135.7, 136.8, 137.5, 138.0, 160.8; IR (KBr) max 3062, 3020, 1734, 1587, 1439, 1275, 1093,
735 cm-1. Anal. Calcd for C21H14O2S: C 76.34; H 4.27. Found: C 76.40; H 4.13.
2-Isopropylidene-4H-3,1-benzoxathiin-4-one (4c): mp 77.1-77.6 °C (AcOEt-hexane); Rf (CH2Cl2 :
hexane = 3:1) 0.55. 1H-NMR (400 MHz, CDCl3) δ 1.86 (3H, s), 1.91 (3H, s), 7.25-7.27 (2H, m), 7.47 (1H,
td, J = 7.8, 1.5 Hz), 8.14 (1H, d, J = 7.8 Hz); 13C-NMR (100 MHz, CDCl3) δ 17.6, 19.8, 123.2, 124.0, 125.7,
126.2, 131.0, 132.4, 133.9, 138.0, 162.1; (KBr) max 2918, 1741, 1655, 1442, 1286, 1227, 1139, 1122, 1099,
739 cm-1. Anal. Calcd for C11H10O2S: C 64.05; H 4.89. Found: C 64.20; H 4.79.
(E)-2-Benzylidene-4H-3,1-benzoxathiin-4-one (4d): mp 84.9-85.5 °C (AcOEt-hexane); Rf (CH2Cl2 :
hexane = 2:1) 0.5; 1H-NMR (400 MHz, CDCl3) δ 6.09 (1H, s), 7.25-7.38 (5H, m), 7.51 (1H, td, J = 7.8, 1.6
Hz), 7.68 (2H, d, J = 7.8 Hz), 8.17 (1H, dd, J = 8.0, 1.6 Hz); 13C-NMR (100 MHz, CDCl3) δ 116.9, 122.0,
125.5, 126.6, 128.0, 128.6, 129.1, 132.5, 133.0, 134.5, 137.2, 137.6, 160.4; IR (KBr) max 3055, 3025, 1737,
1622, 1586, 1265, 1101, 733 cm-1. Anal. Calcd for C15H10O2S: C 70.84; H 3.96. Found: C 70.91; H 3.88.
(E)-2-(4-Chlorobenzylidene)-4H-3,1-benzoxathiin-4-one (4e): mp 131-132 °C (AcOEt-hexane); Rf
(CH2Cl2 : hexane = 2: 1) 0.5; 1H-NMR (400 MHz, CDCl3) δ 6.03 (1H, s), 7.25 (1H, dd, J = 7.6, 1.2 Hz),
7.29-7.33 (3H, m), 7.52 (1H, td, J = 7.6, 1.2 Hz), 7.61 (2H, dt, J = 8.4, 2.4 Hz), 8.16 (1H, dd, J = 7.6, 1.2

HETEROCYCLES, Vol. 89, No. 4, 2014
989
Hz); 13C-NMR (100 MHz, CDCl3) δ 115.4, 121.8, 125.5, 126.7, 128.8, 130.3, 131.5, 132.6, 133.6, 134.6,
136.9, 138.3, 160.0; IR (KBr) max 3048, 1743, 1584, 1442, 1265, 1102, 854, 736 cm-1. Anal. Calcd for
C15H9ClO2S: C 62.39; H 3.14. Found: C 62.18; H 3.11.
(E)-2-(4-Methoxybenzylidene)-4H-3,1-benzoxathiin-4-one (4f): mp 95.8-96.6 °C (AcOEt-hexane); Rf
(CH2Cl2 : hexane = 4:1 ) 0.6; 1H-NMR (400 MHz, CDCl3) δ 3.82 (3H, s), 6.05 (1H, s), 6.89 (2H, d, J = 8.7
Hz ), 7.26-7.30 (2H, m), 7.51 (1H, td, J = 8.0, 1.2 Hz), 7.64 (2H, d, J = 8.7 Hz), 8.17 (1H, dd, J = 8.0, 1.2
13
Hz); C-NMR (100 MHz, CDCl3) δ 55.3, 114.0, 117.0, 122.3, 125.5, 125.9, 126.5, 130.6, 132.6, 134.4,
135.4, 137.7, 159.3, 160.7; IR (KBr) max 2991, 1733, 1604, 1506, 1440, 1260, 1233, 1176, 1103, 1032, 849,
739 cm-1. Anal. Calcd for C16H12O3S: C 67.59; H 4.25. Found: C 67.65; H 4.17.
(E)-2-Phenoxymethylene-4H-3,1-benzoxathiin-4-one (4g: major product): mp 110-111 °C (AcOEt-
hexane); Rf (CH2Cl2 : hexane = 4 : 1) 0.6; 1H-NMR (400 MHz, CDCl3) δ 6.51 (1H, s), 7.03 (2H, m), 7.10
(1H, t, J = 7.5 Hz), 7.27-7.35 (4H, m), 7.51 (1H, td, J = 7.5, 1.2 Hz), 8.17 (1H, dd, J = 7.5, 1.2 Hz);
13C-NMR (100 MHz, CDCl3) δ 116.5, 123.8, 123.9, 125.9, 126.1, 126.9, 129.7, 130.9, 132.9, 134.2, 137.7,
156.6, 160.7; IR (KBr) max 3073, 1745, 1673, 1590, 1487, 1438, 1220, 1092, 767, 739, 692 cm-1. Anal.
Calcd for C15H10O3S: C 66.65; H 3.73. Found: C 66.78; H 3.63.
(Z)-2-Phenoxymethylene-4H-3,1-benzoxathiin-4-one (4’g: minor product): oil; Rf (CH2Cl2 : hexane =
4 : 1) 0.6; 1H-NMR (400 MHz, CDCl3) δ 6.99-7.12 (4H, m), 7.25-7.34 (4H, m), 7.50 (1H, td, J = 7.5, 1.2
Hz), 8.17 (1H, dd, J = 7.5, 1.2 Hz); 13C-NMR (100 MHz, CDCl3) δ 116.1, 122.3, 123.6, 125.9, 126.5, 130.0,
131.0, 132.7, 134.3, 134.4, 136.7, 156.4, 161.3; IR (KBr) max 3061, 1743, 1591, 1490, 1440, 1226, 1140,
740, 688 cm-1; HRMS (EI): Calcd for C15H10O3S: 270.0351. Found: 270.0362.
(E)-2-Methoxymethylene-4H-3,1-benzoxathiin-4-one (4h: major product): mp 81.7-82.8 °C (AcOEt-
hexane); Rf (CH2Cl2 : hexane = 5: 1) 0.4; 1H-NMR (400 MHz, CDCl3) δ 3.74 (3H, s), 6.02 (1H, s), 7.23 (1H,
dd, J = 8.0, 0.8 Hz), 7.29 (1H, td, J = 7.8, 1.2 Hz), 7.46 (1H, td, J = 7.8, 1.2 Hz), 8.14 (1H, dd, J = 7.8, 1.6
Hz); 13C-NMR (100 MHz, CDCl3) δ 61.0, 121.4, 124.1, 125.7, 126.6, 132.8, 133.9, 137.1, 138.8, 161.3; IR
(KBr) max 2937, 1737, 1666, 1440, 1276, 1221, 1143, 1100, 974, 741 cm-1. Anal. Calcd for C10H8O3S: C
57.68; H 3.87. Found: C 57.79; H 3.80.
(Z)-2-Methoxymethylene-4H-3,1-benzoxathiin-4-one (4’h: minor product): mp 72.4-73.9 °C (AcOEt-
hexane); Rf (CH2Cl2 : hexane =5:1) 0.5; 1H-NMR (400 MHz, CDCl3) δ 3.71 (3H, s), 6.72 (1H, s), 7.25-7.27
(2H, m), 7.47 (1H, td, J = 7.8, 1.4 Hz), 8.14 (1H, dd, J = 7.8, 1.4 Hz); 13C-NMR (100 MHz, CDCl3): 60.9,
122.9, 125.2, 125.9, 126.3, 132.7, 134.1, 137.6, 140.8, 162.1; IR (KBr) max 2941, 1738, 1666, 1440, 1278,
1221, 1149, 1099, 983, 741 cm-1. Anal. Calcd for C10H8O3S: C 57.68; H 3.87. Found: C 57.66; H 3.77.
(E)-2-Acetoxymethylene-4H-3,1-benzoxathiin-4-one (4i: major product): mp 138-139 °C (AcOEt-
hexane); Rf (CH2Cl2 : hexane = 5:1) 0.4; 1H-NMR (400 MHz, CDCl3) δ2.23 (3H, s), 7.16 (1H, s), 7.27 (1H,

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HETEROCYCLES, Vol. 89, No. 4, 2014
d, J = 7.8 Hz), 7.33 (1H, td, J = 7.8, 1.4 Hz), 7.52 (1H, td, J = 7.8, 1.4 Hz), 8.15 (1H, dd, J = 7.8, 1.4 Hz);
13C-NMR (100 MHz, CDCl3) δ 20.5, 123.1, 123.4, 126.1, 127.0, 128.1, 132.8, 134.4, 136.7, 160.2, 166.6;
IR (KBr) max 3095, 1751, 1587, 1439, 1377, 1215, 1098, 1051, 945, 822, 737 cm-1. Anal. Calcd for
C11H8O4S: C 55.92; H 3.41. Found: C 56.04; H 3.31.
(Z)-2-Acetoxymethylene-4H-3,1-benzoxathiin-4-one (4’i: minor product): mp 93.2-94.7 °C (AcOEt-
hexane); Rf (CH2Cl2 : hexane = 5:1) 0.35; 1H-NMR (400 MHz, CDCl3) δ 2.23 (3H, s), 7.27 (1H, d, J = 7.7
Hz), 7.31 (1H, td, J = 7.7, 1.2 Hz), 7.52 (1H, td, J = 7.7, 1.2 Hz), 7.69 (1H, s), 8.16 (1H, dd, J = 7.7, 1.2 Hz);
13C-NMR (100 MHz, CDCl3) δ 20.5, 122.0, 125.8, 126.8, 128.7, 132.0, 132.7, 134.6, 135.7, 160.7, 166.6;
IR (KBr) max 3093, 1750, 1592, 1442, 1370, 1196, 1139, 1030, 909, 799, 737 cm-1. Anal. Calcd for
C11H8O4S: C 55.92; H 3.41. Found: C 55.97; H 3.30.
2-Ethylidene-4H-3,1-benzoxathiin-4-one (4j): a mixture of stereoisomers (E : Z = 1 : 1); Oil; 1H-NMR
(400 MHz, CDCl3) δ 1.77 (1.5H, d, J = 7.2 Hz), 1.82 (1.5H, d, J = 7.2 Hz), 5.34 (0.5H, q, J = 7.2 Hz), 5.76
(0.5H, q, J = 7.2 Hz), 7.21 (0.5H, d, J = 8.0 Hz), 7.25-7.30 (1.5H, m), 7.48 (0.5H, td, J = 8.0, 1.4 Hz), 7.49
(0.5H, td, J = 8.0, 1.4 Hz), 8.13 (0.5H, dd, J = 8.0, 1.4 Hz), 8.14 (0.5H, dd, J = 8.0, 1.4 Hz); IR (KBr) max
2921, 1740, 1649, 1594, 1294, 1227, 1139, 1122, 1099, 740 cm-1; HRMS (EI): Calcd for C15H10O3S:
270.0351: Found: 270.0362.
General procedure for oxidation of 4 or 4’.To a solution of 4 or 4’ (1.0 mmol) in CH2Cl2 (10 mL) was
added 70% mCPBA (1.0 mmol, 247 mg). The mixture was stirred for 30 min at room temperature, and then
aqueous Na2SO3 was added. The products were extracted with CH2Cl2, and the organic layer was washed
with water and dried over MgSO4. The solvent was evaporated under reduced pressure, and the crude
product was purified by silica gel column chromatography (eluent 5:1 CH2Cl2 : AcOEt). Crude 5d, 5e, and
5f were recrystallized from AcOEt–hexane.
(E)-2-Benzylidene-4H-3,1-benzoxathiin-4-one 1-oxide (5d): mp 88.0-90.6 °C (AcOEt-hexane);
1H-NMR (400 MHz, CDCl3) δ 6.67 (1H, s), 7.37-7.43 (3H, m), 7.73-7.77 (3H, m), 7.84-7.91 (2H, m), 8.16
(1H, dd, J = 8.0, 1.2 Hz); 13C-NMR (100 MHz, CDCl3) δ 119.3, 121.4, 126.8, 128.9, 130.0, 130.4, 131.0,
132.6, 132.7, 135.4, 142.3, 147.1, 158.7; IR (KBr) max 3055, 3025, 1747, 1639, 1586, 1446, 1266, 1238,
1082, 1055, 1036, 867, 749, 689 cm-1; HRMS (EI): C15H10O3S: 270.0351: Found: 270.0340.
(E)-2-(4-Chlorobenzylidene)-4H-3,1-benzoxathiin-4-one 1-oxide (5e): mp 65.3-66.9 °C (AcOEt-
hexane); 1H-NMR (400 MHz, CDCl3) δ 6.63 (1H, s), 7.38 (2H, dt, J = 8.8, 2.3 Hz), 7.70 (2H, dt, J = 8.8, 2.3
Hz), 7.76 (1H, td, J = 7.8, 1.2 Hz), 7.86-7.92 (2H, m), 8.27(1H, dd, J = 7.8, 1.2 Hz); 13C-NMR (100 MHz,
CDCl3) δ 117.8, 121.2, 126.7, 129.2, 129.4, 131.5, 132.6, 132.8, 135.5, 135.9, 142.1, 147.6, 158.5; IR
(KBr) max 3043, 1753, 1587, 1488, 1406, 1265, 1233, 1089, 1031, 869, 743 cm-1; HRMS (EI):
C15H9ClO3S: 303.9961: Found: 303.9937.

HETEROCYCLES, Vol. 89, No. 4, 2014
991
(E)-2-(4-Methoxybenzylidene)-4H-3,1-benzoxathiin-4-one 1-oxide (5f): mp 93.1-95.3 °C (AcOEt-
hexane); 1H-NMR (400 MHz, CDCl3) δ 3.84 (3H, s), 6.61 (1H, s), 6.93 (2H, d, J = 8.0 Hz), 7.74-7.76 (3H,
m), 7.85-7.87 (2H, m), 8.29 (1H, dd, J = 7.6, 1.2 Hz); 13C-NMR (100 MHz, CDCl3) δ 55.4, 114.3, 120.4,
121.7, 123.7, 127.3, 132.4, 132.6, 132.9, 135.3, 142.0, 144.9, 159.0, 160.9; IR (KBr) max 3005, 1752, 1604,
1511, 1255, 1179, 1086, 1055, 872, 748, 688 cm-1; HRMS (EI): Calcd for C16H12O4S: 300.0456: Found:
300.0449.
(E)-2-Phenoxymethylene-4H-3,1-benzoxathiin-4-one 1-oxide (5g): mp 145-146 °C (AcOEt-hexane); Rf
(CH2Cl2 : AcOEt = 5:1) 0.5; 1H-NMR (400 MHz, CDCl3) δ 7.07 (1H, s), 7.11 (2H, dd, J = 8.4, 1.2 Hz),
7.21 (1H, t, J = 7.2 Hz), 7.38 (2H, t, J = 8.0 Hz), 7.79-7.89 (3H, m), 8.39 (1H, dd, J = 7.6, 1.2 Hz); 13C-NMR
(100 MHz, CDCl3) δ 117.1, 122.6, 125.3, 128.5, 130.1, 132.8, 133.5, 135.1, 135.7, 137.5, 141.1, 156.2,
158.4; IR (KBr) max 3077, 1741, 1669, 1589, 1487, 1441, 1227, 1162, 1062, 1041, 752, 695 cm-1. Anal.
Calcd for C15H10O4S: C 62.93; H 3.52. Found: C 62.83; H 3.43.
(Z)-2-Phenoxymethylene-4H-3,1-benzoxathiin-4-one 1-oxide (5’g): mp 132-134 °C (AcOEt-hexane); Rf
(CH2Cl2 : AcOEt = 5 : 1) 0.6; 1H-NMR (400 MHz, CDCl3) δ 7.07 (2H, d, J = 8.0 Hz), 7.20 (1H, t, J = 7.8
Hz), 7.37 (1H, s), 7.39 (2H, t, J = 8.0 Hz), 7.81-7.88 (2H, m), 7.93 (1H, dd, J = 7.8, 1.8 Hz), 8.39 (1H, dd, J
= 7.8, 1.8 Hz); 13C-NMR (100 MHz, CDCl3) δ 116.6, 122.5, 125.0, 129.5, 130.1, 132.8, 133.8, 135.1, 139.2,
140.3, 141.0, 155.9, 159.5; IR (KBr) max 3039, 1749, 1651, 1588, 1490, 1229, 1141, 1036, 857, 749, 686
cm-1. Anal. Calcd for C15H10O4S: C 62.93; H 3.52. Found: C 62.69; H 3.39.
(E)-2-Methoxymethylene-4H-3,1-benzoxathiin-4-one 1-oxide (5h): mp 107-108 °C (AcOEt-hexane); Rf
(CH2Cl2 : AcOEt = 5:1) 0.4; 1H-NMR (400 MHz, CDCl3) δ 3.94 (3H, s), 6.61 (1H, s), 7.76-7.84 (3H, m),
8.35 (1H, dd, J = 6.8, 1.2 Hz); 13C-NMR (100 MHz, CDCl3) δ 62.5, 122.5, 128.5, 132.7, 132.8, 133.3, 135.0,
141.3, 143.2, 158.6; IR (KBr) max 3065, 2945, 1747, 1670, 1443, 1233, 1119, 1042, 968, 740, 868, 745,
687 cm-1. Anal. Calcd for C10H8O4S: C 53.56; H 3.60. Found: C 53.63; H 3.51.
(Z)-2-Methoxymethylene-4H-3,1-benzoxathiin-4-one 1-oxide (5’h): mp 126-128 °C (AcOEt-hexane);
Rf (CH2Cl2 : AcOEt = 5 : 1) 0.5; 1H-NMR (400 MHz, CDCl3) δ 3.87 (3H, s), 6.97 (1H, s), 7.77-7.84 (2H, m),
7.88 (1H, dd, J = 7.6, 1.6 Hz), 8.34 (1H, dd, J = 7.6, 1.6 Hz); 13C-NMR (100 MHz, CDCl3) δ 62.3, 122.7,
129.4, 132.6, 133.5, 134.9, 135.3, 140.6, 147.1, 159.9; IR (KBr) max 2941, 1738, 1440, 1278, 1221, 1149,
1099, 740 cm-1. Anal. Calcd for C10H8O4S: C 53.56; H 3.60. Found: C 53.60; H 3.47.
(E)-2-Acetoxymethylene-4H-3,1-benzoxathiin-4-one 1-oxide (5i): mp 124-125 °C (AcOEt-hexane); Rf
(CH2Cl2 : AcOEt = 5 : 1) 0.6; 1H-NMR (400 MHz, CDCl3) δ 2.30 (3H, s), 7.72 (1H, s), 7.80-7.89 (3H, m),
8.35 (1H, dd, J = 7.1, 1.6 Hz) 13C-NMR (100 MHz, CDCl3) δ 20.4, 122.3, 128.0, 128.5, 132.9, 133.7, 135.3,
137.4, 140.9, 158.0, 165.9; IR (KBr) max 3107, 1777, 1747, 1677, 1589, 1441, 1377, 1200, 1136, 1091,
1038, 943, 814, 745, 699 cm-1. Anal. Calcd for C11H8O5S: C 52.38; H 3.20. Found: C 52.34; H 3.07.

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(Z)-2-Acetoxymethylene-4H-3,1-benzoxathiin-4-one 1-oxide (5’i): mp 109-110 °C (AcOEt-hexane); Rf
(CH2Cl2 : AcOEt = 5 : 1) 0.6; 1H-NMR (400 MHz, CDCl3) δ 2.30 (3H, s), 7.82-7.92 (3H, m), 7.93 (1H, s),
8.36 (1H, dd, J = 7.5, 1.6 Hz); 13C-NMR (100 MHz, CDCl3) δ 20.4, 122.6, 129.5, 133.0, 133.1, 134.1, 135.1,
139.9, 140.5, 159.0, 165.9; IR (KBr) max 3043, 1766, 1659, 1370, 1202, 1140, 1057, 909, 791, 746, 672
cm-1; HRMS (EI): Calcd for C11H8O5S: 250.0092: Found: 250.0084.
Crystallographic data for (E)-2-(phenoxymethylene)-4H-3,1-benzoxathiin-4-one (4g). C15H10O3S,
Mw = 270.30, colorless, size: 0.35 × 0.33 × 0.29 mm, monoclinic, space group P121/c1, Z = 8, a = 7.2603(3)
Å, b = 20.3891(9) Å, c = 16.7487(7) Å, α = 90.0000°, β = 92.2290(10)°, γ = 90.0000°, V = 2477.45(19) Å3,
D = 1.449 g/cm3, T = 153(2) K, λ = 0.71069 Å, μ = 0.261 mm-1; 13,782 reflections measured, of which 5582
were unique (Rint = 0.0158), R1 = 0.0358 (I > 2σ(I)), Rw = 0.0836 (all data), goodness of fit = 1.036. The
structure was solved by heavy-atom methods and refined on F2 using all the reflections. All the
non-hydrogen atoms were refined using anisotropic atomic displacement parameters, and hydrogen atoms
were placed at calculated positions and included in the refinements using the riding model. Deposition
number
CCDC-985453.
Free
copies
of
the
data
can
be
obtained
at
http://www.ccdc.cam.ac.uk/conts/retrieving.html (or from the Cambridge Crystallographic Data Centre, 12
Union Road, Cambridge, CB2 1EZ, UK; fax: +44 1223 336033; e-mail: deposit@ccdc.cam.ac.uk).
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