Novel Conversion of 6H-1,3,5-Oxathiazine S-Oxides into 5-Membered Heterocyclic Compounds

Article abstract of DOI:10.1002/hc.20004

5H-1,2,4-oxathiazoles were efficiently synthesized from 6H-1,3,5-oxathiazine S-oxides by thermal cycloreversion of the substrates and the products were effectively converted into 1,2,4-thiadiazoles.

Full text of DOI:10.1002/hc.20004

Heteroatom Chemistry
Volume 15, Number 2, 2004
Novel Conversion of 6H-1,3,5-Oxathiazine
S-Oxides into 5-Membered Heterocyclic
Compounds
Islam Md. Rafiqul,1 Kazuaki Shimada,1 Shigenobu Aoyagi,1
Yuji Takikawa,1 and Chizuko Kabuto2
1Department of Chemical Engineering, Faculty of Engineering, Iwate University, Morioka,
Iwate 020-8551, Japan
2Instrumental Analysis Center for Chemistry, Faculty of Science, Tohoku University,
Sendai 980-8578, Japan
Received 26 November 2003; revised 25 December 2003
heterocumulene-like structures and potential build-
ABSTRACT: 5H-1,2,4-oxathiazoles were efficiently
ing blocks toward the synthesis of sulfur containing
heterocyclic compounds. However, only a very lim-
ited studies concerning the heterodienes conjugated
with a sulfine or sulfene framework have been real-
ized due to the preparative difficulties of their pre-
cursors and lack of suitable trapping methods for
these highly reactive species [1–15]. In the course
synthesized from 6H-1,3,5-oxathiazine S-oxides by
thermal cycloreversion of the substrates and the prod-
ucts were effectively converted into 1,2,4-thiadiazoles.
ꢀ
C
2004 Wiley Periodicals, Inc. Heteroatom Chem 15:175–
186, 2004; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20004
of studies on highly-reactive heterodienes possessing
chalcogen functionalities, several groups, including
ours, have reported a convenient generation of 1,3-
thiaza-1,3-butadienes A through thermal cyclorever-
sion of 6H-1,3,5-oxathiazines 3 [16–19].
We envisaged that highly reactive 1,3-thiaza-1,3-
butadiene S-oxides B would be generated through
thermal cycloreversion of 6H-1,3,5-oxathiazine S-
oxides 4 and their subsequent facile ring closure
might give hitherto unknown 5H-1,2,4-oxathiazoles
5 as shown in Scheme 1. In accordance with our ex-
pectation, we successfully synthesized 5 via the most
likely intermediate B. The synthetic applications of
newly synthesized 5 were also explored. In this pa-
per, we would like to report a full account of the new
approach [20].
INTRODUCTION
Heterocyclic compounds containing nitrogen, sulfur,
and oxygen atoms have a great synthetic importance
in the light of their potential biological profiles and
multifunctional utilities. Various reactive intermedi-
ates containing nitrogen and sulfur functionalities in
the same substructures have been developed as ver-
satile building blocks for the synthesis of such hete-
rocycles. Recently, a great deal of interest has been
focused on the preparation and synthetic applica-
tion of ꢀ,ꢁ-unsaturated thione S-oxides due to their
Correspondence to: Yuji Takikawa; e-mail: takikawa@iwate-u.
ac.jp.
Contract grant sponsor: The Foundation for Japanese Chemical
Research.
RESULTS AND DISCUSSION
Contract grant number: 333(R).
Contract grant sponsor: MEXT, Japan Government.
6H-1,3,5-oxathiazines 3a–m were prepared as sin-
c
ꢀ
2004 Wiley Periodicals, Inc.
gle stereoisomers by treating an alkanethioamide
175

176 Rafiqul et al.
arable 3:1 epimeric mixtures of unstable compounds
ascribed to 4h–k besides recovered substrates 3h–k
(ca. 25%). In contrast, mCPBA oxidation of 3l and
3m afforded complex mixtures. All results concern-
ing mCPBA oxidation of 3a–m are shown in Table 1.
The complete relative stereochemistry of the
S O bond and the substituents at the C-2 and C-6
positions of 4 was determined to be equatorially-
oriented by using X-ray crystallographic analysis of
4d, and the ORTEP drawing is shown in Fig. 1.
Heating of a CHCl3 or a benzene solution of
S-oxides 4a–f at refluxing temperature for several
hours afforded 5H-1,2,4-oxathiazoles 5a–f in high
yields. The purification of 5a–f was carried out by
evacuation of volatile aldehydes at room tempera-
ture.
(O)n
R1
(O)n
S
R1
R1
R2
S
S
∆
O
N
O
N
- R2CHO
N
(n=1)
R2
R2
R2
3 (n = 0)
4 (n = 1)
A (n = 0)
B (n = 1)
5
SCHEME 1
or an arenethioamide with an aliphatic aldehyde
and BF3·OEt2 according to the reported procedures
[19–21]. The physical data of the compounds 3a–m
were fully consistent with their assigned structures.
The relative stereochemistry of these products was
confirmed to be cis-configuration in all cases by NOE
measurements [22]. All results for the preparation of
3a–m are shown in Table 1.
When a CHCl3 solution of 3a–g was treated with
mCPBA (1.1 mol amt) at 0◦C for 1 h, the correspond-
ing S-oxides 4a–g were obtained as single epimers in
quantitative yields. The stereoselective formation of
compounds 4a–g might be due to the presence of a
bulky substituent such as t-butyl or isopropyl group
at the C-2 position of 3a–g. The treatment of 3h–k
bearing a methyl or n-butyl group at the C-2 and C-6
positions with mCPBA (1.1 mol amt) afforded insep-
When a CDCl3 solution of 4a was kept stand-
◦
ing in an NMR tube at 25 C, a gradual increase
1
in the intensities of the H NMR and 13C NMR sig-
nals of 5a and pivalaldehyde was observed along with
gradual decrease of the signals of 4a. After standing
the resulting solution for 300 h, a 1:1 mixture of 5a
and pivalaldehyde along with a small amount of 3,5-
diphenyl-1,2,4-thiadiazoles 6a was observed. This re-
sult might suggest that thermal cycloreversion of 4a
would generate 1,3-thiaza-1,3-butadiene S-oxide B,
which subsequently causes facile ring closure to give
TABLE 1 Preparation of 6H-1,3,5-oxathiazines 3 and 6H-1,3,5-oxathiazine S-Oxides 4
O
S
R1
R2 mCPBA (1.1 mol amt) R1
NaHCO3, CHCl3, 0 °C, 1 h
R2
R2CHO (2)
S
S
R1
NH2
.
BF3 OEt2 (2 mol amt)
CHCl3 , R.T. , 2--5h
N
O
N
O
R2
3
R2
4
1
Yield (%)
Entry
R1
R2
3a
4 (major:minor)
1
2
3
4
5
6
7
8
9
10
11
12
13
C H5
t-C4H9
t-C4H9
t-C4H9
t-C4H9
t-C4H9
i -C H7
t-C34H9
CH3
CH3
CH3
n-C4H9
t-C4H9
CH3
43 (3a)
32 (3b)
25 (3c)
45 (3d)
44 (3e)
21 (3f)
38 (3g)
95 (3h)
38 (3i)
91 (3j)
74 (3k)
15 (31)
76 (3m)
96a (4a, 100:0)
98a (4b, 100:0)
98a (4c, 100:0)
99a (4d, 100:0)
97a (4e, 100:0)
95a (4f, 100:0)
97a (4g, 100:0)
74b (4h, 3:1)c
76b (4i, 3:1)c
p-C6IC6H4
p-FC6H4
p-CH3OC6H4
1-Naphthyl
C6H5
CH3
C6H5
p-CIC6H4
p-FC6H4
C6H5
75b (4j, 3:1)c
73b (4k, 3:1)c
Complex mixture
Complex mixture
t-C4H9
CH3
aIsolated yields.
bBased on the integration of 1H NMR.
cDetermined by the integration of the 1H NMR spectra.

Novel Conversion of 6H-1,3,5-Oxathiazine S-Oxides into 5-Membered Heterocyclic Compounds 177
◦
◦
˚
FIGURE 1 ORTEP drawing of 4d. Selected bond lengths (A), bond angles ( ), and torsion angles ( ): S1-O1 = 1.489(2);
S1-C3 = 1.863(2); N1-C3 = 1.264(3); S1-C1 = 1.849(2); O2-C2 = 1.432(2); O1-S1-C1 = 109.5(10); S1-C1-C10 = 114.0(1);
O2-C1-C10 = 111.2(2); O2-C2-C14 = 107.8(2); S1-C1-O2-C2 = 82.9(2); O1-S1-C1-C10 = 76.1(2).
5a. Further standing of the resulting mixture for an
additional 500 h led to a 1:4 mixture of 6a and pi-
valaldehyde along with precipitation of elemental
sulfur.
tion of 8d suggested that the push-pull type sub-
stituent effect of the electron-donating substituent,
p-methoxyphenyl group, might accelerate the C S
bond cleavage. However, the stereoselective oxida-
tion of 5 was not successful even when the oxida-
tion was carried out at −78◦C. The products 7, ex-
cept 7f, were relatively stable toward the storage
at room temperature and in contact with silica gel.
Thermolysis of 4g in benzene at refluxing tem-
perature for 4 h only gave a complex mixture. On
the other hand, thermal reaction of the crude mix-
ture of 4h–k under similar conditions afforded in-
separable products involving 5h–k. In fact, the mix-
tures were converted into the corresponding 1,2,4-
thiadiazoles 6 through the contact with silica gel.
When a CDCl3 solution of the isomeric mixture of
4h (major:minor = 3:1) was kept standing in an NMR
tube at room temperature for about a month, charac-
teristic new signals at δ = 1.45 ppm (d) and 6.30 ppm
(q), most likely assigned to the methyl and methine
protons of 5h, respectively, were observed along with
the early disappearance of the minor isomer of 4h in
the solution. This result suggests that the minor iso-
mer of 4h is more reactive toward thermal cyclore-
version.
1
The physical data, including MS, IR, H NMR, and
13C NMR spectra, as well as elemental analysis data
were fully consistent with the structures of novel 3-
aryl-5-alkyl-5H-1,2,4-oxathiazole S-oxides 7a–f. Fur-
thermore, these results unequivocally confirm the
5H-1,2,4-oxathiazole ring system in compound 5.
The results of the oxidation of 5 are summarized
in Table 3.
Heating of an ethanolic solution of 4a at reflux-
ing temperature for 26 h gave thioamide 9a [19] in
12% yield along with 6a (35%) and small amount of
unidentified products, and in this case, deoxygenated
product 3a was not found at all in crude reaction
mixture. On the other hand, heating of an ethanolic
solution of 5a did not afford thioamide 9a, instead
partial conversion of 5a into 6a was found. This re-
sult indicates that 9a is formed through the pathway
involving the formation of heterodiene B followed
by addition of ethanol to B and the subsequent de-
oxygenation of the resulting thioamide S-oxide C as
shown in Scheme 2. Metzner reported that sulfine,
very similar to the intermediate C, was deoxygenated
through a plausible intermediate oxathiirane by elec-
trocyclization and the subsequent oxygen atom was
extruded under thermal condition [23]. We reported
that when a toluene solution of 3 was heated in
refluxing temperature in the presence of ethanol,
The physical data, including MS, IR, 1H
NMR, and 13C NMR spectra, were fully consis-
tent with the structures of 3-aryl-5-alkyl-5H-1,2,4-
oxathiazoles 5a–f. The oily compounds 5a–f were
labile toward the storage, so little deviation in their
elemental analysis data to those of calculated ones
was observed. All results of the thermal reaction of
4 are summarized in Table 2.
The preparation of stable derivatives of 5 was
attempted. The oxidation of 5a–f by mCPBA at 0◦C
afforded 3:1 oily inseparable epimers of 7a–f. In the
case of mCPBA oxidation of 5d, nitrile 8d was af-
forded as a minor product along with the epimeric
mixture of the expected S-oxides 7d. The forma-

178 Rafiqul et al.
TABLE 2 Thermal Reaction of 6H-1,3,5-oxathiazine S-Oxides 4
O
S
R1
R1
+
R1
S
S
R2
∆
N
O
- R2CHO
N
O
N
N
R1
R2
4
R2
6
5
Substrate
R2
Yield (%)
Entry
R1
4
Solvent
Temp (◦C)
Time (h)
5a
6
R2CHO
b
1
2
3
4
5
6
7
8
9
10
11
12
13
C H5
C6H5
t-C4H9
t-C4H9
t-C4H9
t-C4H9
t-C4H9
t-C4H9
t-C4H9
i -C H7
t-C34H9
CH3
4a
4a
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
C6H6
CDCI3
CDCI3
C6H6
C6H6
C6H6
C6H6
C6H6
C6H6
C6H6
C6H6
C6H6
C6H6
Reflux
25
25
6
300
800
6
5
4
4
4
4
4
92 (5a)
85c (5a)
0 (5a)
0
–
15c
55c
C6H5
Quant
0
0
0
0
0
Quantc
6
b
p-CIC6H4
p-FC6H4
p-CH3OC6H4
1-naphthyl
C6H5
CH3
C6H5
p-CIC6H4
p-FC6H4
C6H5
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
93 (5b)
91 (5c)
96 (5d)
91 (5e)
89 (5f)
–
b
–
b
–
b
–
b
–
Complex mixture
d
e
b
–
–
–
–
–
–
–
–
d
e
b
CH3
CH3
n-C4H9
4
4
5
–
d
e
b
–
d
e
b
–
–
aIsolated yields.
bAldehydes were assumed to get away during the heating.
cYields based on the integration of 1H NMR spectrum of the reaction mixture.
dCompound 5 was not isolated from the thermal reaction products of the epimeric mixtures of 4.
eObserved in the 1H NMR spectrum of crude product of the thermal reaction of 4.
the 1,4-adduct 9 of heterodiene A was obtained in
excellent yield [19]. In contrast, heating of the com-
pound 4 afforded 5, but did not give deoxygenated
product 3. These results exclude out the possibility
of the involvement of heterodiene A in the forma-
tion of compound 9. However, attempts for trapping
of B using 2,3-dimethyl-1,3-butadiene, acetylenes, or
allyltrimethylsilane were unsuccessful.
When a CDCl3 solution of 5a was heated at 100◦C
for 12 h in a sealed NMR tube, a 1:1 mixture of nitrile
8a and pivalaldehyde along with elemental sulfur
was formed. Treatment of a CHCl3 solution of 5b
with Ph3P (1.1 mol amt) at room temperature for 2
h afforded nitrile 8b (89%) and Ph3P S (86%) ex-
clusively. Reaction of 5b with benzylamine (1.2 mol
amt) in CHCl3 at room temperature for 12 h also af-
forded 8b (93%). It is assumed that thiophilic attack
of Ph3P or benzylamine onto the sulfur atom of 5a
causes S O bond fission to accelarate retro [2+2+1]-
type cycloreversion.
TABLE 3 Oxidation of 5H-1,2,4-oxathiazoles 5 by mCPBA
O
R1
R1
S
S
mCPBA (1.1 mol amt)
O
+
R-CN
O
N
N
NaHCO3, CHCl3 , 0 °C, 1 h
R2
R2
7
8
5
Substrate
Yield (%)a
It was found that 1,2,4-thiadiazoles 6 were effi-
ciently obtained through the contact of 5 with silica
gel as shown in Table 4.
Entry
R1
R2
5
7 (major:minor)b
8
Treating a benzene solution of 5a with p-
toluenesulfonic acid (1.1 mol amt) also gave a similar
result. An independent H NMR monitoring experi-
1
2
3
4
5
6
C H5
t-C4H9 5a
t-C4H9 5b
t-C4H9 5c
88 (3:1)
91 (3:1)
89 (3:1)
72 (3:1)
87 (3:1)
56 (3:1)
0
0
0
21
0
0
p-C6IC6H4
p-FC6H4
1
ment for 5a at 25◦C in CDCl3 also showed that the in-
tensity of the signals for 5a was gradually decreased
and the signals ascribed to 6a were increased along
with those of pivalaldehyde. After 20 days, a mix-
ture of 6a and pivalaldehyde in 1:2 molar ratio was
p-MeOC6H4 t-C4H9 5d
1-Naphthyl
C6H5
t-C4H9 5e
i -C3H7 5f
aIsolated yields.
bRatios were determined by integration of the 1H NMR spectra.

Novel Conversion of 6H-1,3,5-Oxathiazine S-Oxides into 5-Membered Heterocyclic Compounds 179
O
S
O
S
O
S
R1
R1
R1
HN
R2
R1
HN
R1
S
∆
S
EtOH
∆
- [O]
N
+
N
O
- R2CHO
OEt
N
OEt
N
R2
R1
(ref. 23)
R2
C
R2
9
R2
B
4
6
∆
9
EtOH
O
R1
R1
R1
S
R2
S
S
mCPBA
O
O
N
O
N
N
R2
R2
R2
5
3
7
∆ or Ph3P or
PhCH2NH2
R1-CN
8
SCHEME 2 Plausible formation pathway of 5–9.
afforded along with precipitated elemental sulfur.
Moreover, heating of a CHCl3 solution of 5a at reflux-
ing temperature for overnight gave a trace amount
of 6a along with the recovery of 5a. It was thought
that prolonged standing of CDCl3 or CHCl3 generates
DCl or HCl, respectively, which might accelerate the
ring cleavage of 5 and then subsequently lead to 6.
When 4a was directly treated with a Lewis acid,
benzonitrile (9a) was mainly obtained along with
small amounts of 6a, 2,4,6-triphenyl-1,3,5-triazine
TABLE 4 Reaction of 5H-1,2,4-oxathiazoles 5 with Lewis Acids
R1
R1
S
S
Lewis acid
N
+
R1-CN
O
N
R.T.
N
R1
R2
5
6
8
Substrates
Yield (%)a
Entry
R1
R2
5
Lewis Acid (Mol Amt) Solvent Time (h)
6
8
Recovery (%)
1
2
3
4
5
6
7
8
9
C H5
6
C6H5
p-CIC6H4
p-FC6H4
p-CH3OC6H4 t-C4H9 5d
1-Naphthyl
C6H5
t-C4H9 5a
t-C4H9 5a
t-C4H9 5a
t-C4H9 5b
t-C4H9 5c
Silica gel (excess)
p-TsOH(2.0)
C6H6
C6H6
CDCI3
C6H6
C6H6
C6H6
C6H6
C6H6
C6H6
C6H6
C6H6
C6H6
1
24
800
1
1
1
1
1
1
1
82 (6a)
0
0
0
0
0
0
0
21
20
0
0
0
0
0
C6H5
Quant (6a)
Quant (6a)c
54 (6b)
DCIb
Silica gel (excess)
Silica gel (excess)
Silica gel (excess)
Silica gel (excess)
Silica gel (excess)
Silica gel (excess)
Silica gel (excess)
Silica gel (excess)
Silica gel (excess)
60 (6c)
0
57 (6d)
31 (8d)
t-C4H9 5e
i -C3H7 5f
76 (6e)
0
0
0
0
0
0
79 (6a)
C6H5
CH3
CH3
CH3
n-C4H9
50 (6a)c
51 (6b)c
53 (6c)c
56 (6a)c
d
d
10
11
12
p-CIC6H4
p-FC6H4
C6H5
d
1
1
0
0
d
aIsolated yields.
bIt was assumed that DCI was generated through decomposition of CDCI3.
cEstimated yield was based on the relative integrationof the 1H NMR signals.
dThe epimeric mixture of 4 was heated, and then the resulting mixture was taken in contact with silica gel.
e The yields were based on the starting 3.

180 Rafiqul et al.
TABLE 5 Reaction of 6H-1,3,5-oxathiazine S-Oxide 4a with
thiadiazoles 6 through oxidative dimerization of pri-
mary thioamides are widely recognized [30–35].
With the above precedent in hand and taking our
findings into account, now we would like to propose
a plausible pathway for the conversion of 5 into 6
through acid-induced hydrolytic fragmentation of 5
as shown in Scheme 3. Lewis acid might coordinate
with oxygen atom of 5 to form F via intermediate E.
The subsequent hydrolysis of F might lead to inter-
mediacy, thioamide S-oxide G. Our previous findings
showed that when thioamide S-oxide was treated
with electrophilic reagents or Lewis acids, the corre-
sponding 3,5-disubstituted 1,2,4-thiadiazole was ef-
ficiently afforded [33]. In the present case, it was as-
sumed that the resulting thioamide S-oxides G might
also cause self-condensation by contact with silica
gel or p-toluenesulfonic acid to give 6. On the other
hand, nitrile 9 would afford by acid-induced ring fis-
sion of 4 via intermediate H.
Lewis Acids
O
Ph
Ph
N
Ph
S
Ph
S
t-Bu
Lewis acid
+
N
+
PhCN
N
N
N
O
CHCl3, R.T.
N
Ph
t-Bu
Ph
4a
6a
8a
11a
Yield (%)a
8a 11a
52
Entry Lewis Acid (Mol Amt) Time (h)
6a
1
2
3
p-TsOH (1.0)
BF3·OEt2 (1.0)
SiO2 (excess)
3
2
2
14
17
28
8
46 12
39
6
aIsolated yields.
11a, and some unidentified compounds as shown in
Table 5.
Several authors reported the formation of 1,2,4-
thiadiazoles 6 through the intermediary nitrile sul-
fides D [24–29]. When a CHCl3 solution of 4a or
5a was heated in the presence of DMAD, the pos-
sible cycloadduct 10 was not found at all in the
crude reaction products. However, we could not fully
exclude out the pathway involving D in the for-
mation of 6 at this time. On the other hand, an-
other alternative pathway for the formation of 1,2,4-
CONCLUSION
We have synthesized novel 5H-1,2,4-oxathiazoles
5 ring system through thermal cycloreversion of
6H-1,3,5-oxathiazines S-oxides 4 and the synthetic
application of 5 into five-membered heterocyclic
compounds containing nitrogen, oxygen, and sulfur
atoms including 3,5-disubstituted 1,2,4-thiadiazoles
6 was also explored.
O
R1
R1
S
R1
S
S
R2
∆
∆
O
R1
C
N S
- R2CHO
N
- R2CHO
N
N
O
N
D
R2
R2
R1
5
DMAD
4
Lewis acid
(E+)
6
- R2CHO
R1
N
S
Lewis acid
(E+)
R1
S
O E
R2
MeO2C
N
-H2O
CO2Me
10
H+
- 1/8 S
8
E
E
O
E
R1
O
S
R2
R1
R1
S
S
R1CN
9
H2O
- R2CHO
O
(ref. 33)
N
O
NH2
N
R2
R2
F
G
H
SCHEME 3 Plausible mechanism for the formation of 6, and 9 (from 4).

Novel Conversion of 6H-1,3,5-Oxathiazine S-Oxides into 5-Membered Heterocyclic Compounds 181
EXPERIMENTAL
General
(decomp.); MS m/z (%) 309 (M+; 2), 252 (M+ − t-
C4H9; 42), 223 (M+ − t-C4H9CHO; 5), 139 (p-
FC6H4CS; 36), 103 (bp); IR (KBr) 2954, 1610, 1506,
1
Melting points were measured in open capillary
tubes with a Buchi 535 micro-melting point appa-
ratus and are uncorrected. H NMR spectra were
1478, 1362, 1237, 1068, 837 cm−1; H NMR (CDCl3)
δ 1.05 (9H, s), 1.06 (9H, s), 4.82 (1H, s), 4.97 (1H,
s), 7.06 (2H, t, JH-F = JH-H = 8.6 Hz), 7.85 (2H, dd,
JH-H = 8.6 Hz, JH-F = 5.3 Hz); 13C NMR (CDCl3) δ
25.1 (q), 25.3 (q), 36.1 (s), 36.9 (s), 88.8 (s), 96.9 (br
s), 115.2 (dd, JC-F = 21.6 Hz), 128.3 (dd, JC-F = 8.6
Hz), 135.4 (d, JC-F = 2.5 Hz), 156.4 (s), 164.2 (d,
JC-F = 248.0 Hz). Found: C, 65.90; H, 7.80; N, 4.55%.
Calcd for C17H24FNOS: C, 65.98; H, 7.82; N, 4.53%.
1
determined at 400 MHz (Bruker AC-400P spectrom-
eter), and 13C NMR spectra were determined at
100 MHz (Bruker AC-400P spectrometer). Chemi-
cal shifts are expressed in parts per million (δ units)
downfield from tetramethylsilane (TMS) used as an
internal reference. Mass spectra were recorded on
a Hitachi M-2000 mass spectrometer with electron-
impact ionization at 20 or 70 eV using a direct inlet
system. IR spectra were recorded for thin film (neat)
or KBr disks on a JASCO FT/IR-7300 spectrometer.
Elemental analyses were performed using a Yanagi-
moto CHN recorder MT-5. Column chromatography
was performed using silica gel (Merck, Cat. No. 7734)
without pretreatment. All substrates and reagents
were commercially available reagent grade and were
used without further pretreatment.
2,6-Di-tert-butyl-4-(p-methoxyphenyl)-6H-1,3,5-
oxathiazine (3d). Colorless needles, mp 101◦C; MS
m/z (%) 321 (M+; 2), 264 (M+ − C4H9; bp); IR (neat)
1
2914, 2353, 1683, 1538, 1071, 562 cm−1; H NMR
(400 MHz, CDCl3): δ 1.05 (9H, s), 1.06 (9H, s), 3.82
(3H,s), 4.82 (1H, s), 4.94 (1H, s), 6.89 (2H, d, J = 9.0
Hz), 7.81 (2H, d, J = 8.8 Hz); 13C NMR (CDCl3): δ
25.1 (q) 25.3 (q), 36.0 (s), 36.9 (s), 55.36 (q), 88.6 (s),
96.8 (br s), 113.5 (d), 127.8 (d), 132.0 (s), 156.5 (s),
161.6 (s); Found: C, 67.21; H, 8.51; N, 4.39%. Calcd
for C18H27NO2S : C, 67.25; H, 8.47; N, 4.36%.
General Procedure for the Preparation of
2,4,6-Trisubstituted 6H-1,3,5-oxathiazines (3)
2,6-Di-tert-butyl-4-naphthalen-1-yl-6H-1,3,5-
oxathiazine (3e). Colorless crystals; mp 54–56◦C
(decomp.); MS m/z (%) 341 (M+; 7), 284 (M+− C4H9;
50), 254 (bp); IR (neat): 2908, 1619, 1460, 1362,
1097, 1063, 999, 799 cm−1; 1H NMR (CDCl3): δ
1.05 (9H, s), 1.11 (9H, s), 4.77 (1H, s), 5.15 (1H, s),
7.42–7.51 (3H, m), 7.63 (1H, d, J = 7.1 Hz), 7.82
(2H, dd, J = 13.1, 6.7 Hz), 8.40 (1H, d, J = 8.2 Hz);
13C NMR (CDCl3): δ 24.9 (q), 25.4 (q), 36.1 (s), 36.6
(s), 89.4 (br s), 97.3 (br s), 124.9 (s), 125.4 (d), 126.0
(s), 126.1 (d), 126.4 (d), 128.1 (d), 129.7 (d), 133.8
(s), 137.8 (s), 159.6 (s); Found: C, 74.23; H, 8.21; N,
4.07%. Calcd for C21H27NOS: C, 73.86; H, 7.97; N,
4.10%.
A 20 ml chloroform solution of alkanethioamide or
an arenethioamide 1 (10.0 mmol) was treated with
2,4,6-trimethyl-1,3,5-trioxane (paraldehyde 2a, 1.04
g, 8.00 mmol), pivalaldehyde (2b, 2.06 g, 24.0 mmol),
pentanal (2c, 2.06 g, 24.0 mmol), or isobutyralde-
hyde (2d, 1.73 g, 24.0 mmol) and BF3·OEt2 (2.84 g,
20 mmol) at 0◦C, and the reaction mixture was stirred
for 4–5 h at room temperature. The reaction mixture
was then quenched with an aqueous NaHCO3 solu-
tion, and was extracted with chloroform. The organic
layer was washed with water, and was dried over
anhydrous Na2SO4. After removing the solvent in
vacuo, the crude product was purified using column
chromatography on silica gel to afford 2,6-dialkyl-4-
aryl-6H-1,3,5-oxathiazine or 2,4,6-trialkyl-6H-1,3,5-
oxathiazine (3) in good yields. Further purification
of solidified products was carried out by recrystal-
lization using hexane.
2,6-Diisopropyl-4-phenyl-6H-1,3,5-oxathiazine
(3f). Pale yellow oil; MS m/z (%) 263 (M+; 74), 191
(bp); IR (neat): 2967, 1615, 1470, 763 cm−1; 1H NMR
(CDCl3): δ 1.05 (6H, dd, J = 6.2, 6.1 Hz), 1.08 (6H,
dd, J = 6.3, 6.2 Hz), 2.06 (1H, quint, J = 6.5 Hz),
2.16 (1H, quint, J = 6.5 Hz), 5.00 (1H, d, J = 1.5
Hz), 5.01 (1H, d, J = 2.5 Hz), 7.36–7.42 (3H, m),
7.82–7.84 (2H, m); 13C NMR (CDCl3): 17.2 (q), 17.4
(q), 17.6 (q), 17.7 (q), 33.9 (d), 34.2 (d), 85.3 (d), 94.2
(d), 126.3 (d), 128.2 (d), 130.7 (d), 139.0 (s), 157.5
(s); Found: C, 67.96; H, 7.97; N, 4.31%. Calcd for
C15H21NOS: C, 68.40; H, 8.04; N, 4.32%.
2,6-Di-tert-butyl-4-phenyl-6H-1,3,5-oxathiazine
(3a). Colorless plates, mp 95.1–95.9◦C (Lit. [19],
95.4–96.0◦C).
2,6-Di-tert-butyl-4-(p-chlorophenyl)-6H-1,3,5-
oxathiazine (3b). Colorless crystals, mp 95.5–96.1◦C
(decomp.) (Lit. [19], 95.4–96.0◦C decomp.).
2,6-Di-tert-butyl-4-(p-fluorophenyl)-6H-1,3,5-
2,6-Di-tert-butyl-4-methyl-6H-1,3,5-oxathiazine
oxathiazine (3c). Colorless plates, mp 55.5–56.5◦C
(3g). Colorless plates, mp 58.4–58.8 ◦C; MS m/z

182 Rafiqul et al.
(%) 229 (M+; 1), 38 (bp); IR (KBr) 2958, 2868, 1642,
1478, 1460, 1204, 1091 cm−1; 1H NMR (CDCl3)
δ 1.97 (9H, s), 0.98 (9H, s), 2.14 (3H, s), 4.49
(1H, s), 4.87 (1H, s); 13C NMR (CDCl3) δ 24.9 (q),
25.1 (q), 29.0 (q), 35.8 (s), 36.2 (s), 88.4 (br s),
96.5 (d), 157.3 (s); Found: C, 62.48; H, 9.96; N,
6.06%. Calcd for C12H23NOS: C, 62.83; H, 10.11; N,
6.11%.
2,4,6-Tri-tert-butyl-6H-1,3,5-oxathiazine (3l).
Colorless plates, mp 59.0–60.0◦C; MS m/z (%) 271
(M+; 9), 214 (M+ − t-C4H9; 66), 188 (M+ − t-C4H9CN;
99), 130 (bp); IR (KBr) 2964, 1625, 1479, 1361, 1068
1
cm−1; H NMR (CDCl3) δ 0.96 (9H, s), 0.98 (9H, s),
1.17 (9H, s), 4.57 (1H, s), 4.76 (1H, s); 13C NMR
(CDCl3) δ 25.1 (q), 28.3 (q), 30.8 (q), 30.9 (s), 36.5
(s), 42.5 (s), 87.8 (d), 96.1 (d), 136.5 (s). Found: C,
65.90; H, 10.71; N, 5.07%. Calcd for C15H29NOS: C,
66.37; H, 10.77; N, 5.16%.
2,6-Dimethyl-4-phenyl-6H-1,3,5-oxathiazine (3h).
Pale yellow oil, (Lit. [19]); MS m/z (%) 207 (M+;
17), 165 (21), 39 (bp); IR (neat) 2985, 1614, 1447,
1373, 1323, 1231, 1161, 1114, 961, 766, 692, cm−1;
1H NMR (CDCl3): δ 1.60 (3H, d, J = 6.1 Hz), 1.61
(3H, d, J = 6.2 Hz), 5.28 (1H, q, J = 6.2 Hz), 5.35
(1H, q, J = 6.1 Hz), 7.35–7.43 (3H, m), 7.78–7.80
(2H, m); 13C NMR (CDCl3): 22.2 (q), 22.5 (q), 75.6
(s), 87.4 (d), 126.2 (d), 128.3 (d), 130.7 (d), 138.5 (s),
157.0 (s); Found: C, 63.45; H, 6.54; N, 6.37%. Calcd
for C11H13NOS: C, 63.74; H, 6.32; N, 6.76%.
2,4,6-Trimethyl-6H-1,3,5-oxathiazine (3m). Pale
1
yellow oil, (Lit. [21]); MS m/z (%) 145 (M+; 1); H
NMR (CDCl3): δ 1.50 (3H, d, J = 6.2 Hz), 1.52 (3H,
d, J = 6.1 Hz), 2.13 (3H, s), 5.04 (1H, m), 5.20 (1H,
q, J = 6.1 Hz).
Preparation of 2,4,6-Trisubstituted
6H-1,3,5-oxathiazine S-Oxides (4) by mCPBA
Oxidation of 6H-1,3,5-oxathiazines (3)
A
chloroform solution (20 ml) of 6H-1,3,5-
4-(p-Chlorophenyl)-2,6-dimethyl-6H-1,3,5-oxa-
thiazine (3i). Colorless needles, mp 101.8–102.3◦C
(decomp.) (Lit. [19], 101.9–102.5◦C (decomp.)).
oxathiazine (3, 1.0 mmol) was treated with mCPBA
(1.1 mol amt) at 0◦C in the presence of NaHCO3 (2
mol amt). The reaction mixture was quenched with
aqueous Na2SO3 solution and was extracted with
chloroform. The mixture was then subjected to the
usual workup. After removing the solvent in vacuo,
product 4 was found in almost quantitative yield as
single epimers (4a–g), or diastereomeric mixtures
(4h–k).
2,6-Dimethyl-4-(p-fluorophenyl)-6H-1,3,5-oxa-
thiazine (3j). Pale yellow plates; mp 47–48 ◦C
(decomp.); MS m/z (%) 226 (M+ − 1; 75), 185
(M+− CH3CHO, 24), 139 (bp); IR (KBr) 2986, 1603,
1
1508, 1232, 1155, 962, 842 cm−1; H NMR (CDCl3)
δ 1.60 (3H, d, J = 6.1 Hz), 1.61 (3H, d, J = 6.1
Hz), 5.27 (1H, q, J = 6.1 Hz), 5.34 (1H, q, J = 6.1
Hz), 7.06 (2H, t, J = 8.6 Hz), 7.79 (2H, dd, J = 8.6,
5.4 Hz); 13C NMR (CDCl3) δ 22.2 (q), 22.4 (q), 75.6
(s), 87.3 (d), 115.2 (dd, JC-F = 21.7 Hz), 128.2 (dd,
JC-F = 8.7 Hz), 134.6 (d, JC-F = 2.8 Hz), 155.7 (s),
164.3 (d, JC-F = 249.9 Hz); Found: C, 58.42; H, 5.29;
N, 6.12%. Calcd for C11H12FNOS: C, 58.65; H, 5.37;
N, 6.22%.
2,6-Di-tert-butyl-4-phenyl-6H-1,3,5-oxathiazine
S-Oxide (4a). Pale yellow oil; MS m/z (%) 221
(M+ − t-C4H9CHO; 15), 164 (M+ − t-C4H9CHO - t-
C4H9; bp); IR (neat) 2961, 2870, 1634, 1479, 1365,
1
1064, 769, 690, 638 cm−1; H NMR (CDCl3) δ 1.01
(9H, s), 1.21 (9H, s), 4.25 (1H, s), 4.99 (1H, s),
7.41–7.47 (3H, m), 7.91–7.93 (2H, m); 13C NMR
(CDCl3) δ 24.9 (q), 25.6 (q), 35.8 (s), 37.0 (s), 97.7
(d), 98.6 (d), 128.9 (d), 129.9 (d), 130.8 (d), 132.0 (s),
163.3 (s). Found: C, 66.17; H, 8.10; N, 4.64%. Calcd
for C17H25NO2S: C, 66.41; H, 8.20; N, 4.56%.
2,6-Di-n-butyl-4-phenyl-6H-1,3,5-oxathiazine
(3k). Pale yellow oil; MS m/z (%) 292 (M+ + 1; 1),
162 (bp); IR (neat): 2960, 1687, 1615, 1448, 1213,
1080, 1006, 766, 691 cm−1; 1H NMR (CDCl3): δ
0.96 (3H, t, J = 6.1 Hz), 0.99 (3H, t, J = 6.1 Hz),
1.45–1.65 (4H, m), 1.68–1.81 (4H, m), 1.82–1.98
(4H, m), 5.18 (1H, t, J = 3.5 Hz), 5.20 (1H, t, J = 4.0
Hz), 7.35–7.39 (3H, m), 7.79–7.81 (2H, m); 13C NMR
(CDCl3): 13.6 (q), 13.9 (q), 17.8 (t), 38.2 (t), 38.4 (t),
79.5 (d), 90.2 (d), 126.1 (d), 128.1 (d), 130.6 (d),
138.7 (s), 156.8 (s); Found: C, 69.62; H, 8.49; N,
5.02%. Calcd for C17H25NOS: C, 70.06; H, 8.65; N,
4.81%.
2,6-Di-tert-butyl-4-(p-chlorophenyl)-6H-1,3,5-oxa-
thiazine S-Oxide (4b). Pale yellow oil; MS m/z (%)
255 (M+ − t-C4H9CHO; 60), 169 (M+ − 2t-C4H9); 38),
103 (bp); IR (neat) 2960, 2339, 1626, 1592, 1488,
1364, 1092, 1067, 832 cm−1; 1H NMR (CDCl3) δ 1.00
(9H, s), 1.19 (9H, s), 4.24 (1H, s), 4.98 (1H, s), 7.42
(2H, br d, J = 8.0 Hz), 7.87 (2H, br d, J = 8.0 Hz);
13C NMR (CDCl3) δ 25.0 (q), 25.7 (q), 35.9 (s), 37.1
(s), 97.9 (d), 98.9 (br s), 128.6 (d), 130.4 (d), 131.1
(s), 137.3 (s), 162.5 (s). Found: C, 59.21; H, 6.79; N,

Novel Conversion of 6H-1,3,5-Oxathiazine S-Oxides into 5-Membered Heterocyclic Compounds 183
3.95%. Calcd for C17H24ClNO2S: C, 59.72; H, 7.08; N,
4.10%.
(q), 29.4 (d), 33.8 (d), 94.9 (d), 95.7 (d), 127.7 (s),
128.2 (d), 128.8 (d), 131.0 (d), 163.3 (s); Found: C,
63.93; H, 7.41; N, 5.09%. Calcd for C15H21NO2S: C,
64.48; H, 7.58; N, 5.01%.
2,6-Di-tert-butyl-4-(p-fluorophenyl)-6H-1,3,5-oxa-
thiazine S-Oxide (4c). Pale yellow oil; MS m/z (%)
239 (M+ − t-C4H9CHO; 11), 182 (M+ − t-C4H9CHO -
t-C4H9; bp); IR (neat) 2977, 2358, 1633, 1600,
2,6-Di-tert-butyl-4-methyl-6H-1,3,5-oxathiazine
S-Oxide (4g). Pale yellow oil; MS m/z (%) 158
(M+ − t-C4H9CHO; 5), 42 (bp); IR (neat) 2960, 1662,
1541, 1481, 1369, 1255, 1049 cm−1; 1H NMR (CDCl3)
δ 1.95 (9H, s), 1.14 (9H, s), 2.45(3H, d, J = 2.5, 2.4
Hz), 4.02(1 s); 13C NMR (CDCl3) δ 19.6 (q), 24.8 (q),
25.4 (q), 35.6 (s), 36.4 (s), 96.7 (d), 99.0 (d), 165.4
(s); Found: C, 58.93; H, 9.41; N, 5.68%. Calcd for
C12H23NO2S: C, 58.74; H, 9.45; N, 5.71%.
1
1506, 1365, 1234, 1160, 1066, 839 cm−1; H NMR
(CDCl3) δ 1.00 (9H, s), 1.19 (9H, s), 4.24 (1H, s),
4.98 (1H, s), 7.12 (2H, t, J = 8.7 Hz), 7.95 (2H, dd,
J = 8.7, J = 5.4 Hz); 13C NMR (CDCl3) δ 25.0 (q),
25.7 (q), 35.9 (s), 37.1 (s), 97.9 (d), 98.7 (s), 115.5
(dd, JC-F = 21.8 Hz), 128.9 (d, JC-F = 2.5 Hz), 131.3
(dd, JC-F = 8.7 Hz), 162.2 (s), 164.2 (d, JC-F = 250.8
Hz). Found: C, 62.46; H, 7.12; N, 4.28%. Calcd for
C17H24FNO2S: C, 62.74; H, 7.43; N, 4.30%.
Thermal Reaction of 6H-1,3,5-oxathiazine
S-Oxides (4)
2,6-Di-tert-butyl-4-(p-methoxyphenyl)-6H-1,3,5-
oxathiazine S-Oxide (4d). Colorless prisms, mp
84–85◦C; MS m/z (%) 251 (M+ − t-C4H9CHO; 17),
165 (M+ − p-CH3OC6H4CN; 6), 134 (t-C4H9CHOSO;
66), 139 (bp); IR (KBr) 2960, 1604, 1510, 1259, 1175,
A benzene solution (20 ml) of 6H-1,3,5-oxathiazine
S-oxide (4, 1.0 mmol) was heated at refluxing temper-
ature for 4–6 h, and the reaction mixture was cooled
to room temperature. After removing the solvent in
vacuo, 5H-1,2,4-oxathiazoles 5a–g were obtained as
pure products in high yields.
1
1066, 1034 cm−1; H NMR (CDCl3): δ 1.00 (9H, s),
1.19 (9H, s), 3.83 (3H,s), 4.27 (1H,s), 4.96 (1H,s),
6.93 (2H,d, J = 8.9 Hz), 7.92 (2H, d, J = 8.9 Hz);
13C NMR (CDCl3): δ 25.0 (q) 25.6 (q), 35.9 (s), 37.0
(s), 55.3 (q), 97.8 (d), 98.5 (br s), 113.7 (d), 125.3 (s),
130.7 (d), 161.8 (s), 162.0 (s); Found: C, 63.60; H,
7.88; N, 4.19%. Calcd for C18H27NO3S: C, 64.06; H,
8.06; N, 4.15%.
5-tert-Butyl-3-phenyl-5H-1,2,4-oxathiazole (5a).
Pale yellow oil; MS m/z (%) 221 (M+; 18), 164
(M+ − t-C4H9, bp), 57 (t-C4H9, 42); IR (neat) 2959,
1620, 1477, 1450, 1364, 1328, 1056, 969, 765, 714,
689 cm−1; 1H NMR (CDCl3) δ 1.09 (9H, s), 5.89 (1H,
s), 7.40–7.45 (3H, m), 7.47–7.57 (2H, m); 13C NMR
(CDCl3) δ 25.2 (q), 37.3 (s), 123.6 (d), 128.0 (d), 128.8
(d), 130.0 (s), 132.0 (d), 168.2 (s). Found: C, 63.97;
H, 6.69; N, 6.16%. Calcd for C12H15NOS: C, 65.12; H,
6.83; N, 6.33%.
2,6-Di-tert-butyl-4-naphthalen-1-yl-6H-1,3,5-oxa-
thiazine S-Oxide (4e). Pale yellow oil; MS m/z (%)
271 (M+ − t-C4H9CHO; 2), 185 (M+ − 2 - t-C4H9CHO;
3), 153 (C10H7CN; bp); IR (neat): 2963, 1645, 1480,
1365, 1100, 1062, 774 cm−1; 1H NMR (CDCl3): δ
1.06 (9H, s), 1.21 (9H, s), 4.28 (1H, s), 5.15 (1H, s),
7.51-7.53 (3H, m), 7.71 (1H, d, J = 7.0 Hz), 7.87
(1H, d, J = 7.7 Hz), 7.92 (1H, d, J = 8.2 Hz), 8.21
(1H, d, J = 8.3 Hz); 13C NMR (CDCl3): δ 25.1 (q),
25.6 (q), 36.0 (s), 36.9 (s), 97.9 (d), 99.5 (br s), 124.6
(d), 124.9 (d), 126.3 (s), 127.0 (d), 126.4 (d), 128.0
(d), 128.6 (d), 130.6 (d), 130.9 (d), 133.7 (s), 167.1
(s); Found: C, 74.23; H, 8.21; N, 4.07%. Calcd for
C21H27NOS: C, 73.86; H, 7.97; N, 4.10%.
5-tert-Butyl-3-(p-chlorophenyl)-5H-1,2,4-oxathia-
zole (5b). Pale yellow oil; MS m/z (%) 255 (M+;
22), 43 (bp); IR (neat) 2959, 2400, 1621, 1489, 1364,
1092, 971, 833 cm−1; H NMR (CDCl3) δ 1.08 (9H,
1
s), 5.87 (1H, s), 7.42 (2H, br d, J = 8.0 Hz), 7.50
(2H, br d, J = 8.0 Hz); 13C NMR (CDCl3) δ 25.2 (q),
37.4 (s), 123.7 (d), 128.4 (s), 129.2 (d), 129.3 (d),
138.0 (s), 167.2 (s). Found: C, 55.25; H, 5.53; N,
5.27%. Calcd for C12H14ClNOS: C, 56.35; H, 5.52; N,
5.48%.
2,6-Diisopropyl-4-phenyl-6H-1,3,5-oxathiazine S-
Oxide (4f). Pale yellow oil; MS m/z (%) 279 (M+; 5),
207 (M+ − C3H7CHO; 31), 104 (bp); IR (neat): 2970,
1629, 1471, 1035, 761 cm−1; 1H NMR (CDCl3): δ 1.99
(6H, dd, J = 6.8, 6.8 Hz), 1.17 (6H, dd, J = 6.8, 6.8
Hz), 2.12 (1H, quint, J = 3.5 Hz), 2.51 (1H, quint,
J = 3.5 Hz), 4.42 (1H, d, J = 3.5 Hz), 5.19 (1H, d,
J = 4.5 Hz), 7.39–7.48 (3H, m), 7.92–7.94 (2H, m);
13C NMR (CDCl3): 16.2 (q), 16.6 (q), 17.2 (q), 18.2
5-tert-Butyl-3-(p-fluorophenyl)-5H-1,2,4-oxathia-
zole (5c). Pale yellow oil; MS m/z (%) 239 (M+;
4), 41 (bp); IR (neat) 2959, 1621, 1508, 1235, 1156,
1058, 840 cm−1; 1H NMR (CDCl3) δ 1.08 (9H, s),
5.86 (1H, s), 7.12 (2H, t, J = 8.6 Hz), 7.58 (2H, dd,
J = 8.6, J = 5.3 Hz); 13C NMR (CDCl3) δ 25.2 (q),
37.3 (s), 116.0 (dd, JC-F = 22.3 Hz), 123.6 (d), 126.2
(d, JC-F = 2.5 Hz), 130.2 (dd, JC-F = 7.7 Hz), 164.7 (d,

184 Rafiqul et al.
JC-F = 251.4 Hz), 167.0 (s). Found: C, 58.86; H, 5.75;
N, 5.48%. Calcd for C12H15FNOS: C, 60.23; H, 5.90;
N, 5.85%.
3,5-Diphenyl-1,2,4-thiadiazole (6a). Colorless
needles, mp 88.5–89.7◦C (Lit. [33], 91.0◦C).
3,5-Bis-(p-chlorophenyl)-1,2,4-thiadiazole (6b).
Colorless needles, mp 159–161◦C (Lit. [33], 161–
162◦C).
5-tert-Butyl-3-(p-methoxyphenyl)-5H-1,2,4-oxa-
thiazole (5d). Pale yellow oil; MS m/z (%) 251 (M+;
16), 194 (M+ − C4H9, 72), 41 (bp); IR (neat) 2960,
2226, 1608, 1510, 1261, 1173, 1060, 1032, 970, 835
3,5-Bis-(p-fluorophenyl)-1,2,4-thiadiazole (6c).
Colorless needles, mp 185–186◦C; MS m/z (%) 273
(M+ − 1; 98), 88 (bp) 32 (S, 58); IR (KBr) 1598, 1518,
1478, 1411, 1316, 1237, 1158, 1098, 806, 743 cm−1;
1H NMR (CDCl3) δ 1.15–7.25 (6H, m), 8.03–8.06 (2H,
m), 8.35–8.39 (2H, m); 13C NMR (CDCl3) δ 115.8 (dd,
JC-F = 21.1 Hz), 116.6 (dd, JC-F = 21.7 Hz), 127.0 (d,
JC-F = 2.5 Hz), 129.1 (d, JC-F = 2.5 Hz), 129.7 (dd,
JC-F = 8.8 Hz), 130.5 (dd, JC-F = 8.8 Hz), 164.2 (d,
JC-F = 248 Hz), 164.8 (d, JC-F = 248.7 Hz), 169.4 (s),
172.8 (s). Found: C, 61.54; H, 3.21; N, 10.04%. Calcd
for C14H8F2N2S: C, 61.30; H, 2.94; N, 10.21%.
1
cm−1; H NMR (CDCl3) δ 1.07 (9H, s), 3.83 (3H,s),
5.85 (1H, s), 6.91(2H, d, J = 8.7 Hz), 7.52 (2H, d,
J = 8.5 Hz); 13C NMR (CDCl3) δ 25.2 (q), 37.3 (s),
55.3 (q), 113.9 (d), 122.6 (s), 123.4 (d), 129.7 (d),
162.4 (s), 167.4 (s). Found: C, 61.57; H, 6.55; N,
5.42%. Calcd for C13H17NO2S: C, 62.12; H, 6.82; N,
5.57%.
5-tert-Butyl-3-naphthalen-1-yl-5H-1,2,4-oxathia-
zole (5e). Pale yellow oil; MS m/z (%) 271
(M+ − t-C4H9CHO; 2), 239 (M+ − S; 2); 185 (M+ − t-
C4H9CHO; 89), 153 (C10H7CN; bp); IR (neat): 2964,
2222, 1512, 1213, 1142, 802, 773 cm−1; 1H NMR
(CDCl3): δ 1.18(9H, s), 6.06 (1H, s), 7.45–7.62 (3H,
m), 7.95 (1H, d, J = 8.3 Hz), 8.06 (1H, d, J = 8.3
Hz), 8.23 (1H, d, J = 8.3 Hz), 8.93 (1H, d, J = 8.4
Hz); 13C NMR (CDCl3): δ 25.4 (q), 37.4 (s), 110.20
(d), 124.2 (s), 124.7 (d), 124.9 (d), 126.6 (d), 127.5
(d), 127.8 (s), 128.5 (d), 128.6 (d), 132.2 (d), 132.6
(s), 168.0 (s). Found: C, 69.77; H, 6.24; N, 5.11%.
Calcd for C16H17NOS: C, 70.81; H, 6.31; N, 5.16%.
3,5-Bis-(p-methoxyphenyl)-1,2,4-thiadiazole (6d).
Colorless powder, mp 137–138◦C (Lit. [33], 139–
140◦C).
3,5-Di-naphthalen-1-yl-1,2,4-thiadiazole (6e).
Pale yellow oil; MS m/z (%) 338 (M+; 43), 184 (bp),
153 (C10H7CN, 38); IR (neat) 3062, 2222, 1513, 1375,
1
1213, 802, 773 cm−1; H NMR (CDCl3) δ 7.52 (2H,
dd, J = 7.9, 7.5 Hz), 7.61 (2H, dd, J = 7.4, 7.7 Hz),
7.69 (2H, dd, J = 7.9, 7.2 Hz), 7.91 (4H, dd, J = 5.4,
7.0 Hz), 8.07 (2H, d, J = 8.3 Hz), 8.24 (2H, d, J =
8.3 Hz); 13C NMR (CDCl3) δ 117.8 (d), 124.9 (d), 125.1
(d), 127.5 (d), 128.5 (d), 128.6 (d), 132.3 (s), 132.6 (s),
132.9 (s), 133.2 (s), 183.5 (s). Found: C, 78.17; H, 4.13;
N, 8.13%. Calcd for C22H14N2S: C, 78.08; H, 4.17; N,
8.28%.
5-Isopropyl-3-phenyl-5H-1,2,4-oxathiazole (5f).
Pale yellow oil; MS m/z (%) 207 (M+; 19), 164
(M+ − C3H7; bp); IR (neat): 2966, 2230, 1618,
14761328, 1119, 1027, 763, 690 cm−1; 1H NMR
(CDCl3): δ 1.08 (6H, dd, J = 6.8, 6.8 Hz), 2.26
(1H, quint, J = 4.9 Hz), 6.02 (1H, d, J = 4.8 Hz),
7.41–7.51 (3H, m), 7.57–7.59 (2H, m); 13C NMR
(CDCl3): 17.3 (q), 17.6 (q), 33.5 (d), 120.5 (d), 127.4
(s), 128.0 (d), 128.8 (d), 132.0 (d), 168.4 (s). Found:
C, 62.46; H, 6.18; N, 6.33%. Calcd for C11H13NOS: C,
63.73; H, 6.32; N, 6.76%.
Preparation of 5H-1,2,4-oxathiazole S-Oxides 7
by mCPBA Oxidation of 5H-1,2,4-oxathiazoles 5
A
chloroform solution (20 ml) of 5H-1,2,4-
oxathiazoles (5, 1.0 mmol) was treated with mCPBA
(1.1 mol amt) at 0◦C for 1 h in the presence of
NaHCO3 (2 mol amt). The reaction mixture was
quenched with aqueous Na2SO3 solution, and was
extracted with chloroform. The mixture was then
subjected to the usual work up. The solvent was evap-
orated in vacuo, and the crude product was sub-
jected to chromatographic separation on silica gel.
The products were obtained as inseparable epimeric
mixture of 5H-1,2,4-oxathiazole S-oxides 7.
Conversion of 5H-1,2,4-oxathiazoles 5 into
3,5-Disubstituted 1,2,4-Thiadiazoles 6 by the
Treatment of Silica Gel/Lewis Acid
A chloroform solution of 5H-1,2,4-oxathiazoles (5,
1.0 mmol) was transferred onto a column, packed
with silica gel. The crude product was allowed to
stand for an hour. Then separation was performed
by using hexane as eluent. The products 6 were ob-
tained as solid except 6e. The solid products 6 were
purified by recrystallization from hexane.
5-tert-Butyl-3-phenyl-5H-1,2,4-oxathiazole S-
Oxide (7a). Pale yellow oil; MS m/z (%) 237 (M+;
3), 221 (M+ − O, 4); 151 (M+ − t-C4H9CHO, 84), 57

Novel Conversion of 6H-1,3,5-Oxathiazine S-Oxides into 5-Membered Heterocyclic Compounds 185
(t-C4H9, bp); IR (neat) 2967, 1655, 1450, 1367, 1130,
NMR (CDCl3) major isomer δ 25.2 (q), 36.0 (s), 55.4
(s), 103.9 (d), 114.6 (d), 114.7 (d), 123.9 (s), 131.7
(s), 163.1 (s), minor isomer δ 25.8 (q), 36.0 (s), 55.4
(s), 98.2 (d), 119.8 (s), 127.8 (s), 131.8 (d), 133.8 (d),
168.2 (s); Found: C, 57.92; H, 6.37; N, 5.22%. Calcd
for C13H17NO3S: C, 58.40; H, 6.41; N, 5.24%.
952, 792, 770, 689 cm−1; 1H NMR (CDCl3) major
isomer δ 1.06 (9H, s), 6.61 (1H, s), 7.48–7.59 (3H,
m), 8.03–8.05 (2H, m), minor isomer δ 1.12 (9H, s),
6.31 (1H, s), 7.48–7.59 (3H, m), 8.03–8.05 (2H, m);
13C NMR (CDCl3) major isomer δ 25.2 (q), 36.1 (s),
109.1 (d), 127.5 (s), 129.3 (d), 130.0 (d), 132.7 (d),
168.9 (s), minor isomer δ 25.8 (q), 36.0 (s), 127.68
(s), 129.2 (d), 129.9 (d), 132.6 (d), 168.2 (s). Found:
C, 60.67; H, 6.43; N, 6.01%. Calcd for C12H15NO2S:
C, 60.73; H, 6.37; N, 5.90%.
5-tert-Butyl-3-naphthalen-1-yl-5H-1,2,4-oxathia-
zole S-oxide (7e). Pale yellow oil; MS m/z (%) 271
(M+ − t-C4H9CHO; 2), 239 (M+ − S; 2); 185 (M+ − t-
C4H9CHO; 89), 153 (C10H7CN; bp); IR (neat): 2966,
2225, 1639, 1510, 1367, 1129, 1056, 803, 774 cm−1;
1H NMR (CDCl3) major isomer δ 1.13 (9H, s),
6.77 (1H, s), 7.47–7.51 (3H, m), 7.87–7.93 (1H,
m), 8.02–8.06 (1H, m), 8.18–8.23 (1H, m), 9.15 (d,
J = 8.3 Hz), minor isomer δ 1.22 (9H, s), 6.50 (1H,
s), 7.47–7.51 (3H, m), 7.87–7.93 (1H, m), 8.02–8.06
5-tert-Butyl-3-(p-chlorophenyl)-5H-1,2,4-oxathia-
zole S-oxide (7b). Pale yellow oil; MS m/z (%) 270
(M+ − 1; 1), 201 (M+ − t-C4H9CHO, 1); 57 (t-C4H9,
bp), 29; IR (neat) 2963, 1642, 1594, 1489, 1403, 1132,
1
1091, 834 cm−1; H NMR (CDCl3) major isomer δ
1.06 (9H, s), 6.59 (1H, s), 7.50 (2H, d, J = 8.0 Hz),
7.97 (2H, d, J = 8.0 Hz), minor isomer δ 1.12 (9H,
s), 6.30 (1H, s), 7.48 (2H, d, J = 8.0 Hz), 7.99 (2H, d,
J = 8.0 Hz); 13C NMR (CDCl3) major isomer δ 25.2
(q), 36.1 (s), 123.9 (d), 125.9 (s), 129.6 (d), 131.1
(d), 139.1 (s), 167.9 (s), minor isomer δ 25.8 (q),
36.2 (s), 125.8 (s), 127.9 (s), 129.5 (d), 131.0 (d),
139.6 (s), 167.2 (s). Found: C, 53.23; H, 5.29; N,
5.12%. Calcd for C12H14ClNO2S: C, 53.38; H, 5.37; N,
5.08%.
(1H, m), 8.18–8.23 (1H, m), 8.89 (d, J = 8.3 Hz); 13
C
NMR (CDCl3) major isomer δ 25.3 (q), 36.0 (s), 110.1
(d), 124.8 (d), 125.1 (d), 125.6 (s), 127.5 (s), 128.4
(d), 128.5 (d), 128.9 (d), 132.5 (d), 133.2 (d), 133.4
(s), 169.9 (s), minor isomer δ 25.9 (q), 36.4 (s), 110.4
(d), 124.6 (d), 124.8 (d), 125.5 (s), 126.9 (d), 128.3
(s), 131.5 (d), 132.0 (d), 132.3 (d), 132.8 (d), 134.0
(s), 173.6 (s); Found: C, 67.02; H, 6.87; N, 4.52%.
Calcd for C17H21NO2S: C, 67.29; H, 6.98; N, 4.62%.
5-Isopropyl-3-phenyl-5H-1,2,4-oxathiazole S-
Oxide (7f). Pale yellow oil; MS m/z (%) 223 (M+;
3), 180 (M+ − C3H7; 7), 175 (M+ − SO; 10), 159
(M+ − SO2; 8), 151 (M+ − C3H7CHO; 28), 105 (bp);
IR (neat): 2969, 1642, 1473, 1129, 1028, 953, 768,
690 cm−1; 1H NMR (CDCl3) major isomer δ 1.05 (6H,
dd, J = 6.4, 6.4 Hz), 2.28 (1H, quint, J = 4.9 Hz),
6.73 (1H, d, J = 4.8 Hz), 7.43–7.57 (3H, m), 8.03–
8.05 (2H, m), minor isomer δ 1.14 (6H, dd, J = 6.8,
6.8 Hz), 2.28 (1H, quint, J = 4.9 Hz), 6.41 (1H, d,
J = 5.8 Hz), 7.43–7.57 (3H, m), 8.03–8.05 (2H, m);
13C NMR (CDCl3) major isomer δ 16.9 (q), 18.5 (q),
33.3 (d), 124.8 (d), 129.3 (d), 129.9 (s), 130.3 (d),
132.7 (d), 168.9 (s), minor isomer δ 17.4 (q), 18.0
(q), 34.6 (d), 121.2 (d), 128.3 (s), 128.6 (d), 129.2
(d), 132.6 (d), 166.0 (s); Found: C, 58.02; H, 5.75; N,
6.12%. Calcd for C11H13NO2S: C, 59.17; H, 5.87; N,
6.27%.
5-tert-Butyl-3-(p-fluorophenyl)-5H-1,2,4-oxathia-
zole S-oxide (7c). Pale yellow oil; MS m/z (%) 256
(M+ + 1; 8), 169 (M+ − t-C4H9CHO, 30); IR (neat)
1
2966, 1644, 1602, 1509, 1160, 1129, 842 cm−1; H
NMR (CDCl3) major isomer δ 1.05 (9H, s), 6.59
(1H, s), 7.22 (2H, t, J = 8.8 Hz), 8.05–8.10 (2H,
m), minor isomer δ 1.12 (9H, s), 6.30 (1H, s), 7.19
(2H, t, J = 8.6 Hz), 8.05–8.10 (2H, m); 13C NMR
(CDCl3) major isomer δ 25.2 (q), 36.1 (s), 116.3 (dd,
JC-F = 21.7 Hz), 123.8 (d, JC-F = 2.6 Hz), 132.2 (s),
132.3 (dd, JC-F = 8.7 Hz), 165.2 (d, JC-F = 254.3 Hz),
167.8 (s), minor isomer δ 25.8 (q), 36.0 (s), 116.2 (dd,
JC-F = 23.1 Hz), 123.8 (d, JC-F = 2.6 Hz), 127.9 (br s),
132.2 (d, JC-F = 8.7 Hz), 165.2 (d, JC-F = 254.3 Hz),
168.3 (s). Found: C, 56.32; H, 5.47; N, 5.22%.
Calcd for C12H14FNO2S: C, 56.45; H, 5.53; N,
5.49%.
5-tert-Butyl-3-(p-methoxyphenyl)-5H-1,2,4-oxa-
thiazole S-oxide (7d). Pale yellow oil; MS m/z (%)
267 (M+; 7), 251 (M+ − O; 1), 281 (M+ − t-C4H9CHO,
53); 151 (bp); IR (neat) 2963, 2225, 1606, 1511, 1262,
1176, 1127, 1029, 835 cm−1. 1H NMR (CDCl3) major
isomer δ 1.04 (9H, s), 3.87 (3H, s), 6.56 (1H, s), 7.00
(2H, d, J = 8.8 Hz), 7.99 (2H, d, J = 8.5 Hz), minor
isomer δ 1.11 (9H, s), 3.85 (3H, s), 6.27 (1H, s), 6.99
(2H, d, J = 8.7 Hz), 8.00 (2H, d, J = 8.6 Hz); 13C
Heating of 6H-1,3,5-oxathiazine S-Oxides 4
in an Ethanol Media
An ethanol solution (20 ml) of 6H-1,3,5-oxathiazine
S-oxides (4a, 1.0 mmol) was heated at refluxing tem-
perature for 26 h. After cooling to room temperature
and quenching with water, the reaction mixture was
subjected to the usual work up. The crude product
was purified using column chromatography on silica

186 Rafiqul et al.
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gel to afford 3,5-diphenyl-1,2,4-thiadiazole 6a (35%),
N-(1-ethoxy-2,2-dimethylpropyl)thiobenzamide 9a
(12%), along with some unidentified products.
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N-(1-ethoxy-2,2-dimethylpropyl)thiobenzamide
9a. Yellow oil; MS m/z (%) 251 (M+; 50), 222
(M+ − C2H5; 84), 87 (bp); IR (neat) 3397, 3290, 2963,
2904, 1501, 1481, 1449, 1370, 1362, 1116, 1069,
1
961, 736, 693 cm−1; H NMR (CDCl3) δ 1.04 (9H, s),
1.21 (3H, br t, J = 6.9 Hz), 3.64 (1H, dq, J = 9.9,
7.0 Hz), 3.73 (1H, dq, J = 9.9, 6.9 Hz), 5.81 (1H, d,
J = 8.0 Hz), 7.30–7.50 (3H, m), 7.55–7.70 (1H, m),
7.72–7.75 (2H, m); 13C NMR (CDCl3) δ 15.0 (q), 24.9
(q), 36.5 (s), 64.7 (t), 90.4 (d), 126.4 (d), 128.5 (d),
131.1 (d), 142.3 (s), 200.9 (s). Found: C, 66.85; H,
8.76; N, 5.40%. Calcd for C14H21NOS: C, 66.89; H,
8.42; N, 5.57%.
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20, 1537–1538.
X-ray Crystallographic Data for 4d
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Takikawa, Y.; Kabuto, C. Chem Lett 1997, 701–702.
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Colorless prism of 4d suitable for X-ray in-
vestigation was obtained from CHCl3 at −20◦C.
Crystal data: C18H27NO3S, FW = 337.48, crystal
size 0.15 × 0.15 × 0.20 mm3, monoclinic, space
group P21/n (#14), a = 8.778(2), b = 16.711(4), c =
◦
3
˚
˚
12.514(3) A, ß = 97.178(5) , V = 1821.3(8) A , Z = 4,
Dcalc = 1.231 g/cm3, µ = 1.92 cm−1. From 17055 re-
flections measured 4129 were unique (R = 0.030).
int
˚
R = 0.037, Rw = 0.040, MoKα (λ = 0.71070 A, T =
−100.0◦C. The structure was solved by direct meth-
ods (SIR92). Crystallographic data (excluding struc-
ture factors) have been deposited with Cambridge
Crystallographic Data Centre as supplementary pub-
lication no. CCDC 215096. Copies of the data
can be obtained, free of charge, via the Internet
http://www.ccdc.cam.ac.uk, or on application to the
director; CCDC, 12 Union Road, Cambridge CB2
1EZ, UK. Tel. (+44) 1223-336-408; fax: (+44) 1223-
336-033; e-mail: deposit@ccdc.cam.ac.uk.
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