Novel conversion of 6H-1,3,5-oxathiazine S-oxides into 3H-1,2,4-dithiazoles by treating with Lawesson's reagent

Article abstract of DOI:10.1002/hc.20011

Treatment of 6H-1,3,5-oxathiazine S-oxides by Lawesson's reagent (LR) at high temperature furnished 3H-1,2,4-dithiazoles in moderate to good yields. Deoxygenation of 6H-1,3,5-oxathiazine S-oxides was performed by LR in the presence of EtOH.

Full text of DOI:10.1002/hc.20011

Heteroatom Chemistry
Volume 15, Number 3, 2004
Novel Conversion of 6H-1,3,5-Oxathiazine
S-Oxides into 3H-1,2,4-Dithiazoles by
Treating with Lawesson’s Reagent
Islam Md. Rafiqul, Kazuaki Shimada, Shigenobu Aoyagi,
Yoriko Fujisawa, and Yuji Takikawa
Department of Chemical Engineering, Faculty of Engineering, Iwate University, Morioka,
Iwate 020-8551, Japan
Received 15 December 2003; revised 19 January 2004
and synthesis of novel thiosulfoxides have been con-
ABSTRACT: Treatment of 6H-1,3,5-oxathiazine S-
sidered as vibrant area of current research [1–22].
oxides by Lawesson’s reagent (LR) at high temper-
However, only a few methods to generate such
ature furnished 3H-1,2,4-dithiazoles in moderate to
species are available, and one of the general and
good yields. Deoxygenation of 6H-1,3,5-oxathiazine
simple methods to generate such species is the con-
S-oxides was performed by LR in the presence of
version of sulfoxides into the corresponding thio
ꢀ
C
EtOH. 2004 Wiley Periodicals, Inc. Heteroatom Chem
variants by treating with some thiating agents. Con-
cerning thiocarbonyl S-sulfides (thiosulfines) pos-
sessing higher ꢀ-conjugation systems, no methods
15:208–215, 2004; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20011
for the generation of such species has been reported
to date, in spite of their synthetic potentiality of
novel intermediates for new cyclic polysulfide ring
systems.
INTRODUCTION
The importance of sulfur-containing heterocyclic
compounds concerning their unique structures and
biological activities has led to increase in the number
of synthetic methods for the synthesis of various het-
erocyclic compounds, and especially various reactive
species containing thiocarbonyl functionalities have
long been investigated as versatile and useful build-
ing blocks for such heterocycles. However, in con-
trast to the common thiocarbonyl functionalities,
unusual species containing a S S double bond func-
tionality, i.e. thiosulfoxides, have long been proposed
only as intermediates and, in some special cases, as
stable cyclic thiosulfinate esters, and the generation
During our attempts to generate various reac-
tive species bearing a chalcogenocarbonyl fuction-
ality by using the selective ring fission of precursors,
heterocycles, we have already reported novel meth-
ods for the generation of 1,3-thiaza-1,3-butadiene
A and their S-oxides B through retro [4 + 2]-type
thermal cycloreversion of 6H-1,3,5-oxathiazines 1
and 6H-1,3,5-oxathiazine S-oxides 2, respectively
[23,24]. It is strongly expected that the above findings
must be applicable to a new strategy for the corre-
sponding thio-variants, i.e. thiosulfines, through an
analogous cycloreversion of the thio-variants (thio-
sulfoxides C) involving the thiation of 6H-1,3,5-
oxathiazine S-oxides 2 (Scheme 1). Furthermore,
the new thiosulfine-type heterodienes, 1,3-thiaza-
1,3-butadiene S-sulfides D, are expected to un-
dergo facile ring closure to give 3H-1,2,4-dithiazole
3 through a similar manner of conversion of
Correspondence to: Yuji Takikawa; e-mail: takikawa@iwate-u.
ac.jp.
Contract grant sponsor: MEXT, Japan Government.
2004 Wiley Periodicals, Inc.
c
ꢀ
208

Novel Conversion of 6H-1,3,5-Oxathiazine S-Oxides into 3H-1,2,4-Dithiazoles by Treating with Lawesson’s Reagent 209
3H-1,2,4-dithiazoles 3a–h were afforded in moder-
ate to good yields. Characterization of compounds
3a–h was carried out on the basis of microanalyti-
cal, and spectroscopic data (IR, 1H and 13C NMR, and
mass spectrometric data). The use of P2S5 in place of
LR under the similar reaction conditions was also ef-
fective for the conversion of 2 into 3, but the yields of
3 were relatively lower than those cases using LR as
a thiating agent. In contrast, when a toluene solution
of 2 was treated with LR or P2S5 at room tempera-
ture, only a complex mixture was obtained and com-
pounds 3 were found in a trace amount in the crude
reaction mixture. All results of the treatment of 2a–h
with thiating agents are summarized in Table 1.
Plausible Reaction Mechanism of Conversion
of 2 into 3
It is commonly recognized that sulfoxides react with
phosphorus sulfide reagents to afford the corre-
sponding sulfides via the intermediary thiosulfox-
ides [1,2,26–32]. But, in our cases, we could find a
new preparation of 3H-1,2,4-dithiazoles 3 through
the reaction of 2 with LR. 1H and 13C NMR monitor-
ing of the reaction of 2a with LR or P2S5 in CDCl3
in an NMR tube at 25◦C showed the instantaneous
SCHEME 1
1,3-thiaza-1,3-butadiene S-oxides B into the corre-
sponding 5H-1,2,4-oxathiazoles.
According to the expectation shown above, we
started the attempts for the thiation of 2 and the
subsequent heating at an ambient condition. Now,
we would like to report an efficient conversion
of 6H-1,3,5-oxathiazine S-oxides 2 into 3H-1,2,4-
dithiazoles 3 by treating with LR at high temperature
and also wish to demonstrate some salient features
of this transformation.
TABLE 1 Synthesis of 3H-1,2,4-dithiazoles 3 by Treating 2
with a Thiating Agent
RESULTS AND DISCUSSION
Preparation of 6H-1,3,5-Oxathiazine S-Oxides 2
6H-1,3,5-Oxathiazines 1a–h were prepared as single
stereoisomers by treating an alkanethioamide or an
arenethioamide with an aliphatic aldehyde or 2,4,6-
trimethyl-1,3,5-trioxane and BF3·OEt2 according to
the reported procedure [23,25].
When a CHCl3 solution of 1a–f was treated with
mCPBA (1.1 mol amt) at 0◦C, the corresponding S-
oxides 2a–f were afforded as single isomers in quan-
titative yields. The treatment of 1g–h with mCPBA
afforded a mixture of unstable compounds assigned
as the isomers of 2g–h along with recovery of 1g–h
(ca. 25%).
Substrate
Thiating Yield (%)a
Run
R1
R2
2
Agent
3
1
2
3
4
5
6
7
8
9
C6H5
C6H5
t-C4H9 2ab
t-C4H9 2ab
t-C4H9 2bb
t-C4H9 2cb
LR
P2S5
LR
66
57
60
p-ClC6H4
p-FC6H4
LR
62
p-MeOC6H4 t-C4H9 2db
LR
54
α-Naphthyl
t-C4H9 2eb
t-C4H9 2fb
LR
LR
LR
LR
51
CH3
C6H5
C6H5
32c
40e
37e
CH3
2gd
Conversion of 6H-1,3,5-Oxathiazine S-Oxides 2
into 3H-1,2,4-Dithiazoles 3 by the Treatment
with Lawesson’s Reagent or Phosphorus
Pentasulfude
n-C4H9 2hd
aIsolated yield.
bA single stereoisomer.
cUnstable.
When a toluene solution of 2a–h was treated with LR
at refluxing temperature for 1 h, the corresponding
dIsomeric mixture including ca. 25% of oxathiazine 1.
eYield was based on oxathiazine 1.

210 Rafiqul et al.
facile disappearance of 2a along with the formation
of some intermediary compounds, small amounts of
pivalaldehyde, and 3a. In the primary stage, the sim-
ilarity in the patterns of the 1H and 13C spectra of the
intermediate showed the retention of the similar het-
erocyclic ring system to that of the starting 2. When
the above crude reaction mixture was subjected to
standing for an hour, the quantitative formation of
pivalaldehyde was observed along with ring cleav-
age of 2a. However, the isolation of the intermediates
was not successful, and in all cases a complex mix-
ture was obtained as a crude product after the usual
workup of the reaction mixture. It was also notewor-
thy that the deoxygenated product 1a was not ob-
of transiently generated heterodiene B [24]. These re-
sults showed that the deoxygenation pathway of 2a
only by heating was ruled out.
Compounds 2 having a sulfoxide moiety are gen-
erally expected to undergo oxygen-sulfur exchanging
through the treatment with thiating agents via the
four-membered phosphorus- and sulfur-containing
intermediates [1,2,26–32]. Unequivocal mechanism
for the reaction of sulfoxides 2 with a phosphorus
sulfur reagent has not yet been established. Based
on the analogous mechanism proposed during sev-
eral decades for the thiation of sulfoxide with phos-
phorus sulfur reagents [1,2,26–32] and by taking the
present findings into account, the most likely forma-
tion pathway of 3 involving the formation of E and F
through the reaction of 2 with LR is proposed. It was
assumed that E might undergo stepwise mass frag-
mentation involving cycloreversion to give F along
with the formation of pivalaldehyde and the further
removal of PSOAnis from F to give the likely thio-
sulfine intermediates D, which causes facile ring clo-
sure to afford 3 as shown in Scheme 2. However,
an alternative formation pathway of 3 from F by si-
multaneous elimination of PSOAnis and concomi-
tant ring formation through concerted manner can
not be ruled out at this time.
1
served at all in the reaction mixture during the H
NMR monitoring at 25◦C. However, in the mass spec-
trum of the crude product, several characteristic ion
peaks involving a fragment ion peak at m/z 237, as-
signed to D or 3, a peak at m/z 186, assigned to PSOA-
nis fragment, and an ion peak at m/z 86, assigned to
the parent ion peak of pivalaldehyde, were observed
in spite of the lack of any parent ion peak of E and/or
F. Furthermore, when a toluene solution of the crude
products of 2a with LR obtained through the reac-
tion carried out at R.T., was subjected to heating at
refluxing temperature for a few hours, 3a was ob-
tained in 65% yield. In contrast, the similar heating
of 1a in toluene in the presence of LR only afforded
a trace amount of 3a along with the recovery of 1a.
So, the formation of 3 involving the deoxygenation
of 2 and the subsequent thermal reaction of 1 with
LR was excluded out. Independent heating of 2a in
toluene at refluxing temperature in the presence or
absence of elemental sulfur only resulted in the for-
mation of 5H-1,2,4-oxathiazole 4a in almost quan-
titative yield through the pathway involving thermal
cycloreversion of 2a and the subsequent ring closure
Deoxygenation of 6H-1,3,5-Oxathiazine
S-Oxides 2 by the Treatment with LR
in the Presence of Ethanol
Interestingly, deoxygenation of 2a–b was success-
fully performed to give 1a–b in 71 and 69% yield,
respectively, by treating with LR in the presence
of ethanol in CHCl3 at room temperature. On the
other hand, the reaction of 2a with LR in toluene
at refluxing temperature gives 5a in 63% yield as
SCHEME 2 Plausible formation pathway of compounds 3.

Novel Conversion of 6H-1,3,5-Oxathiazine S-Oxides into 3H-1,2,4-Dithiazoles by Treating with Lawesson’s Reagent 211
SCHEME 3 Deoxygenation of 2a by LR-EtOH system.
shown in Scheme 3. The formation of 5a can be
explained by the pathway that the reaction of 2a
with LR-EtOH system initially gives deoxygenation
product 1a and the subsequent thermal cyclorever-
sion of 1a at toluene refluxing temperature generates
1,3-thiaza-1,3-butadiene A, followed by 1,4-addition
of ethanol to the resulting heterodiene A to afford
5a. However, attempts for the detection or trap-
ping of the intermediates in this transformation were
unsuccessful.
acid G, which then follows either path a [33] or path
b [34] for the formation of deoxygenated product 1
as shown in Scheme 4.
CONCLUSION
A novel conversion of 6H-1,3,5-oxathiazine S-oxides
2 into 3H-1,2,4-dithiazoles 3 was achieved by the re-
action of 2 with LR at high temperature, and the in
situ formation of 1,3-thiaza-1,3-butadiene S-sulfides
D through thermal reaction of intermediary phos-
phorus compounds is suggested through the spec-
Two plausible mechanistic pathways for the de-
oxygenation of 2 by LR in the presence of EtOH
could be proposed. In the primary stage, the reac-
tion of LR with EtOH might form dithiophosphoric
1
tral data of the intermediates and the results of H
NMR monitoring of the reaction. On the other hand,
SCHEME 4 Plausible mechanism of the deoxygenation of 2 by LR in the presence of ethanol.

212 Rafiqul et al.
deoxygenation of 2 occurred by the treatment with
LR in the presence of ethanol. Further studies on
the discreet mechanistic investigation and the gen-
eral synthetic expansion of this approach for various
cyclic polysulfides are currently being explored.
2,6-Di-tert-butyl-4-(p-chlorophenyl)-6H-1,3,5-
oxathiazine (1b). 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-
oxathiazine (1c). Colorless plates, mp 55.5–56.5◦C
(decomp.); MS m/z (%) 309 (M+; 2), 252 (M+ − t-
C4H9; 42), 223 (M+ − t-C4H9CHO; 5), 139 (p-
FC6H4CS; 36), 103 (base peak); IR (KBr) 2954, 1610,
EXPERIMENTAL
General
1
1506, 1478, 1362, 1237, 1068, 837 cm−1; H NMR
Melting points were measured in open capillary
tubes with a Buchi 535 micro-melting point appa-
(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
ratus and are uncorrected. H NMR spectra were
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 in-
let system. IR spectra were recorded for thin film
(neat) or KBr disks on a JASCO FT/IR-7300 spec-
trometer. Elemental analyses were performed using
a Yanagimoto CHN recorder MT-5. Column chro-
matography 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 (1d). Colorless needles, mp 101◦C; MS
m/z (%) 321 (M+; 2), 264 (M+ − C4H9; base peak); IR
1
(neat) 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 (1)
A chloroform solution (20 ml) of alkanethioamide
or an arenethioamide (10.0 mmol) was treated with
2,4,6-trimethyl-1,3,5-trioxane (paraldehyde, 1.04 g,
8.00 mmol), pivalaldehyde (2.06 g, 24.0 mmol),
pentanal (2.06 g, 24.0 mmol), or isobutyraldehyde
(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 solution,
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 (1) in good yields. Further purification
of solid products was carried out by recrystallization
from hexane.
2,6-Di-tert-butyl-4-naphthalen-1-yl-6H-1,3,5-oxa-
thiazine (1e). Colorless crystals; mp 54–56◦C (de-
comp.); MS m/z (%) 341 (M+; 7), 284 (M+ − C4H9;
50), 254 (base peak); IR (neat): 2908, 1619, 1460,
1
1362, 1097, 1063, 999, 799 cm−1; H 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%.
2,6-Di-tert-butyl-4-methyl-6H-1,3,5-oxathiazine
(1f). Colorless plates, mp 58.4–58.8◦C; MS m/z (%)
229 (M+; 1), 38 (base peak); IR (KBr) 2958, 2868,
1642, 1478, 1460, 1204, 1091 cm−1; 1H NMR (CDCl3)
δ 0.97 (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
2,6-Di-tert-butyl-4-phenyl-6H-1,3,5-oxathiazine
(1a). Colorless plates, mp 95.1–95.9◦C (Lit. [19],
95.4–96.0◦C).

Novel Conversion of 6H-1,3,5-Oxathiazine S-Oxides into 3H-1,2,4-Dithiazoles by Treating with Lawesson’s Reagent 213
(s). Found: C, 62.48; H, 9.96; N, 6.06%. Calcd for
C12H23NOS: C, 62.83; H, 10.11; N, 6.11%.
2,6-Di-tert-butyl-4-(p-chlorophenyl)-6H-1,3,5-oxa-
thiazine S-Oxide (2b) . Pale yellow oil; MS m/z
(%) 255 (M+ − t-C4H9CHO; 60), 169 (M+ − 2t-C4H9;
38), 103 (base peak); IR (neat) 2960, 2339, 1626,
2,6-Dimethyl-4-phenyl-6H-1,3,5-oxathiazine (1g).
Pale yellow oil, (Lit. 19); MS m/z (%) 207 (M+; 17),
165 (21), 39 (base peak); 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%.
1
1592, 1488, 1364, 1092, 1067, 832 cm−1; H 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, 3.95%. Calcd for C17H24ClNO2S:
C, 59.72; H, 7.08; N, 4.10%.
2,6-Di-tert-butyl-4-(p-fluorophenyl)-6H-1,3,5-oxa-
thiazine S-Oxide (2c). Pale yellow oil; MS m/z (%)
239 (M+ − t-C4H9CHO; 11), 182 (M+ − t-C4H9CHO-
t-C4H9; base peak); IR (neat) 2977, 2358, 1633, 1600,
2,6-Di-n-butyl-4-phenyl-6H-1,3,5-oxathiazine
(1h). Pale yellow oil; MS m/z (%) 292 (M+ + 1; 1),
162 (base peak); IR (neat): 2960, 1687, 1615, 1448,
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%.
1
1213, 1080, 1006, 766, 691 cm−1; H NMR (CDCl3):
δ 0.96 (3H, t, J = 7.4 Hz), 0.99 (3H, t, J = 7.4 Hz),
1.45–1.65 (4H, m), 1.68–1.81 (4H, m), 1.82–1.98 (4H,
m), 5.17–5.22 (2H, m), 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-methoxyphenyl)-6H-1,3,5-
oxathiazine S-Oxide (2d). Colorless prisms, mp
84–85◦C; MS m/z (%) 251 (M+ − t-C4H9CHO; 17),
165 (M+ − p-CH3OC6H4CN; 6), 134 (t-C4H9CHOSO;
66), 139 (base peak); IR (KBr) 2960, 1604, 1510,
Preparation of 2,4,6-Trisubstituted
6H-1,3,5-Oxathiazine S-Oxides (2) by mCPBA
Oxidation of 6H-1,3,5-Oxathiazines (1)
1
1259, 1175, 1066, 1034 cm−1; H NMR (CDCl3): δ
A
chloroform solution (20 ml) of 6H-1,3,5-
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%.
oxathiazine (1, 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 2 was obtained in almost quantita-
tive yield as single isomers (2a–f), or diastereomeric
mixtures (2g–h).
2,6-Di-tert-butyl-4-naphthalen-1-yl-6H-1,3,5-oxa-
thiazine S-Oxide (2e). Pale yellow oil; MS m/z (%)
271 (M+ − t-C4H9CHO; 2), 185 (M+ − 2-t-C4H9CHO;
3), 153 (C10H7CN; base peak); 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%.
2,6-Di-tert-butyl-4-phenyl-6H-1,3,5-oxathiazine
S-Oxide (2a). Pale yellow oil; MS m/z (%) 221
(M+ − t-C4H9CHO; 15), 164 (M+ − t-C4H9CHO-t-
C4H9; base peak); IR (neat) 2961, 2870, 1634, 1479,
1
1365, 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%.

214 Rafiqul et al.
2,6-Di-tert-butyl-4-methyl-6H-1,3,5-oxathiazine
11), 235(M+ − S, 3), 210 (M+−C4H9; base peak); IR
S-Oxide (2f). Pale yellow oil; MS m/z (%) 158
(neat): 2961, 1606, 1509, 1257, 1173, 926, 835, 600
(M+ − t-C4H9CHO; 5), 42 (base peak); IR (neat)
cm−1; H NMR (400 MHz, CDCl3): δ 1.10 (9H, s),
1
1
2960, 1662, 1541, 1481, 1369, 1255, 1049 cm−1; H
3.84 (3H, s), 6.26 (1H, s), 6.91 (2H, d, J = 8.8 Hz),
7.80 (2H, d = 8.8 Hz); 13C NMR (CDCl3): δ 26.7 (q),
38.8 (s), 55.4 (q), 104.0 (d), 113.9 (d), 124.8 (s), 130.7
(d), 139.1 (s), 164.3 (s). Found: C, 58.67; H, 6.23; N,
4.96%. Calcd. for C13H17NOS2: C, 58.39; H, 6.41; N,
5.24%.
NMR (CDCl3) δ 0.95 (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%.
The Thiation and Thermal Reaction of 2
3-tert-Butyl-5-naphthalen-1-yl-3H-1,2,4-dithiazole,
3e. Pale yellow oil; MS m/z (%) 287 (M+; 19), 255
(M+ − S; 49); 230 (M+ − C4H9; 53), 41 (base peak);
IR (neat): 2959, 1738, 1628, 1477, 1364, 1096, 796,
A toluene solution of 2a–h was treated with 1.0 molar
amount of LR at refluxing temperature for 1 h. After
cooling to room temperature, the solvent was evap-
orated in vacuo. The residue was chromatographed
on Al2O3 to afford 3H-1,2,4-dithiazoles 3 in moderate
to good yields.
1
774, 580 cm−1; H NMR (400 MHz, CDCl3): δ 1.21
(9H, s), 6.49 (1H, s), 7.53–7.59 (3H, m), 7.88 (1H, d,
J = 8.3 Hz), 7.93 (1H, d, J = 8.3 Hz), 8.57 (1H, d,
J = 8.4 Hz); 13C NMR (CDCl3): δ 26.9 (q) 38.6 (s),
105.3(d), 124.7 (d), 125.5 (d), 126.5 (s), 127.4 (d),
128.5 (d), 128.6 (d), 129.3 (d), 129.7 (d), 130.5 (d),
131.7 (s), 164.3 (s).
3-tert-Butyl-5-phenyl-3H-1,2,4-dithiazole, 3a.
Pale yellow oil; MS m/z (%) 237 (M+; 18), 205
(M+ − S, 1), 180 (M+ − C4H9; base peak); IR (neat):
2961, 1633, 1448, 1363, 1046, 928, 689, 602 cm−1;
1H NMR (400 MHz, CDCl3): δ 1.13 (9H, s), 6.31 (1H,
s), 7.40–7.48 (3H, m), 7.83–7.85 (2H, m); 13C NMR
(CDCl3): δ 26.7 (q), 38.9 (s), 104.1 (d), 128.7 (d), 128.9
(d), 131.7 (d), 132.1 (s), 165.1 (s). Found: C, 60.91;
H, 6.56; N, 5.89%. Calcd. for C12H15NS2: C, 60.71; H,
6.37; N, 5.90%.
3-tert-Butyl-5-methyl-3H-1,2,4-dithiazole, 3f.
Pale yellow oil; MS m/z (%) 175 (M++1; 2), 64 (base
peak); IR (neat) 2959, 1656, 1463, 1366, 1169, 890,
602 cm−1; 1H NMR (CDCl3) δ 1.04 (9H, s), 2.29 (3H,
s), 6.01 (1H, s); 13C NMR (CDCl3) δ 19.5 (q), 26.5 (q),
38.3 (s), 104.5 (d), 162.6 (s).
3-tert-Butyl-5-(4-chloro-phenyl)-3H-1,2,4-dithi-
azole, 3b. Pale yellow oil; MS m/z (%) 271 (M+;
15), 239(M+ − S, 2), 214 (M+ − C4H9; base peak); IR
(neat): 2961, 1623, 1488, 1363, 1253, 1093, 927, 832,
3-Methyl-5-phenyl-3H-1,2,4-dithiazole, 3g. Red
oil; MS m/z (%) 195 (M+; 61), 163 (M+ − S, 4), 180
(M+−CH3; 2), 104 (base peak); IR (neat): 2925, 1624,
1476, 1443, 1368, 1265, 1089, 920, 765, 689 cm−1; 1H
NMR (CDCl3): δ 1.74 (3H, d, J = 6.4 Hz), 6.34 (1H,
q, J = 6.4 Hz), 7.42–7.50 (3H, m), 7.84–7.86 (2H, m);
13CNMR (CDCl3): 22.5 (q), 85.7 (d), 128.7 (d), 129.1
(d), 131.9 (d), 136.4 (s), 165.8 (s). Found: C, 54.82;
H, 4.41; N, 6.98%. Calcd. for C9H9NS2: C, 55.35; H,
4.64; N, 7.17%.
1
590 cm−1; H NMR (400 MHz, CDCl3): δ 1.10 (9H,
s), 6.29 (1H, s), 7.39 (2H, d, J = 8.4 Hz), 7.77 (2H,
d = 8.5 Hz); 13C NMR (CDCl3): δ 26.7 (q) 38.9 (s),
104.0 (d), 128.4 (s), 128.5 (s), 128.9 (d), 130.2 (d),
69.6 (s). Found: C, 53.28; H, 5.33; N, 4.62%. Calcd.
for C12H14ClNS2: C, 53.02; H, 5.19; N, 5.15%.
3-tert-Butyl-5-(4-fluoro-phenyl)-3H-1,2,4-dithi-
azole, 3c. Pale yellow oil; MS m/z (%) 255 (M+; 18),
(M+ − S, 223), 198 (M+ − C4H9; base peak); IR (neat):
2962, 1629, 1507, 1236, 1046, 929, 840, 601 cm−1;
1H NMR (400 MHz, CDCl3): δ 1.10 (9H, s), 6.28 (1H,
s), 7.10 (2H, t, J = 8.5 Hz), 7.84 (2H, dd = 5.3, 5.4
Hz); 13C NMR (CDCl3): δ 26.6 (q), 38.8 (s), 104.0 (d),
115.7 (d), 115.9 (d), 131.0 (d), 131.1 (d), 163.8 (s),
164.8 (d, J = 251.4 Hz). Found: C, 56.89; H, 5.48; N,
5.17%. Calcd. for C12H14FNS2: C, 56.44; H, 5.53; N,
5.48%.
3-n-Butyl-5-phenyl-3H-1,2,4-dithiazole, 3h. Pale
yellow oil; MS m/z (%) 237 (M+; 1), 180 (M+ − C4H9,
16), 55 (base peak); IR (neat): 2959, 1622, 1622, 1449,
1
1350, 919, 766, 691, 607 cm−1; H NMR (400 MHz,
CDCl3): δ 1.00 (3H, t, J = 7.4 Hz), 1.58 (2H, sex-
tet, J = 7.4 Hz), 1.91–1.96 (2H, m), 2.70–2.13 (2H,
m), 6.31(1H, dd, J = 7.2 Hz, 5.6 Hz), 7.40–7.49 (3H,
m), 7.83–7.85 (2H, m); 13C NMR (CDCl3): δ 13.7 (q),
19.9 (t), 38.6 (t), 91.3 (d), 128.7 (d), 129.1 (d), 131.8
(d), 132.0 (s), 165.6 (s). Found: C, 59.03; H, 5.99; N,
5.86%. Calcd. for C12H15NS2: C, 60.71; H, 6.37; N,
5.90%.
3-tert-Butyl-5-(4-methoxy-phenyl)-3H-1,2,4-dithi-
azole, 3d. Pale yellow oil; MS m/z (%) 267 (M+;

Novel Conversion of 6H-1,3,5-Oxathiazine S-Oxides into 3H-1,2,4-Dithiazoles by Treating with Lawesson’s Reagent 215
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