Access to thiomorpholin-3-one derivatives: [3 + 3]-cycloadditions of α-chlorohydroxamates and 1,4-dithiane-2,5-diol

Article abstract of DOI:10.1016/j.tet.2019.07.019

A protocol of [3 + 3]-cycloaddition was proposed for the synthesis of 2H-1,4-thiazin-3(4H)-ones and thiomorpholine-3,5-diones from α-chlorohydroxamates and 1,4-dithiane-2,5-diol. This direct and practical method provides a novel and rapid approach for the

Full text of DOI:10.1016/j.tet.2019.07.019

Accepted Manuscript
Access to thiomorpholin-3-one derivatives: [3 + 3]-cycloadditions of α-
chlorohydroxamates and 1,4-dithiane-2,5-diol
Zhao-Lin He, Yi Chen, Xiaohua Wang, Mingwang Ni, Gang Wang
PII:
S0040-4020(19)30773-2
https://doi.org/10.1016/j.tet.2019.07.019
TET 30461
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 17 May 2019
Revised Date: 9 July 2019
Accepted Date: 12 July 2019
Please cite this article as: He Z-L, Chen Y, Wang X, Ni M, Wang G, Access to thiomorpholin-3-one
derivatives: [3 + 3]-cycloadditions of α-chlorohydroxamates and 1,4-dithiane-2,5-diol, Tetrahedron
(2019), doi: https://doi.org/10.1016/j.tet.2019.07.019.
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Access to Thiomorpholin-3-one Derivatives:
[3 + 3]-Cycloadditions of α-Chlorohydrox-
amates and 1,4-Dithiane-2,5-diol
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He Zhao-Lina , Chen Yia, Wang Xiaohuab, Ni Mingwanga, and Wang Ganga,
a School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan, 430205, PR China
b Department of Pharmaceutical Engineering, WuChang University of Technology, Wuhan, 430223, PR China

1
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Tetrahedron
journal homepage: www.elsevier.com
Access to Thiomorpholin-3-one Derivatives: [3 + 3]-Cycloadditions of α-
Chlorohydroxamates and 1,4-dithiane-2,5-diol
He Zhao-Lina , Chen Yia, Wang Xiaohuab, Ni Mingwanga, and Wang Ganga,
a School of Chemistry and Environmental Engineering, Wuhan Institute of Technology, Wuhan, 430205, PR China
bDepartment of Pharmaceutical Engineering, WuChang University of Technology, Wuhan, 430223, PR China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A protocol of [3 + 3]-cycloaddition was proposed for the synthesis of 2H-1,4-
thiazin-3(4H)-ones and thiomorpholine-3,5-diones from α-chlorohydroxamates
and 1,4-dithiane-2,5-diol. This direct and pratical method provides a novel and
rapid approach for the synthesis of thiomorpholin-3-one derivatives under mild
condition with moderate to good yield and wide functional group tolerance.
Available online
Keywords:
cycloaddition
2009 Elsevier Ltd. All rights reserved
.
azaoxyallyl cations
1,4-dithiane-2,5-diol
2H-1,4-thiazin-3(4H)-ones
thiomorpholine-3,5-diones
1. Introduction
dienes in the [4 + 3]-cyloadditon reaction, providing bicyclic
lactam derivatives in good yields and diastereoselectivity.8-11
Later in 2015, Jeffrey and Wu independently reported the first
example of dearomative [3 + 2]-cycloaddition reaction of in-situ
Thiomorpholin-3-ones are unique heterocyclic motifs present
in a number of natural products and bioactive molecules with
promising activities, such as shermilamine F is a pyridoacridine
alkaloids isolated from the Ascidian Cystodytes, bafilomycins F
(1) isolated from Streptomyces sp. is a potent inhibitor of
autophagy.1-2 ML276 was found to be a submicromolar
inhibitor of Pf G6PD.3 Fluorescent compound 4, a transcyclized
product of GGT probe NM-GSH, could easily pass through cell-
membrane and enrich in lysosomes and selectively lit up the
GGT overexpressed cancer cells for easy visualization, possesses
the potential for cancer diagnosis and treatment (Figure 1).4 Due
to their bioactivities and medicinal value, the exploration of
efficient methods to build thiomorpholin-3-ones’ frameworks is
of significant importance. Reported methods include: (i) direct
condensation of thioglyco-lates with 2-oxazolidinones,5 (ii) MCR
reaction of diaryl 1,2-diones, thiazolium salts and water,6 (iii)
domino reaction from thioglycolates, aldehydes and ammonia
7
catalyzed by L-proline. Despite the accomplishment of the
aforementioned methods toward constructing thiomorpholin-3-
ones, the development of a more efficient method with facile
accessible substrates is still highly desirable.
Figure 1. Selected examples of natural products and bioactive
compounds containing a thiomorpholin-3-one framework
As a type of transient reactive species, the azaoxyallyl cations
which can be generally in situ generated from α-
halohydroxamates in the presence of bases, In 2010, this
formed azaoxyallyl cations with substituted indoles, providing
rapid access to a variety of functionalized pyrroloindoline
derivatives in good yields.12-13 Since these elegant discoveries,
intermediate was first trapped by Jeffrey’s group using cyclic
———
Corresponding author. Tel.: +86-027-87194560; e-mail: wg@wit.edu.cn

2
Tetrahedron
1
Et3N
THF
THF
THF
THF
THF
THF
THF
THF
THF
DCM
CHCl3
EA
Acetone
CH3CN
Toluene
dioxane
DMF
DMSO
12
12
8
96
24
72
8
24
12
8
8
8
12
8
24
12
4
79
57
71
70
trace
55
73
61
the azaoxyallyl cation species have attracted considerable
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2
3
4
5
6
DIPEA
DIPA
DMAP
DABCO
Na2CO3
K2CO3
EtONa
NaOH
Et3N
Et3N
Et3N
Et3N
Et3N
attention as highly efficient 3-atom units in [3 + m] cycloaddition
reactions for the construction of various biologically important
nitrogen containing heterocycles.14 And a series of [3 + 1]-, [3 +
2]-, and [3 + 3]-cycloaddition reactions have been developed
with azaoxyallyl cations used as versatile surrogates of “1,3-
7
8
dipole” to react with sulfur ylides,15 aldehydes,16 ketones,17-18
imines,19-21 enamines,
isothiocyanides,23 nitrones,24-25 N-
22
9
decomposed
10
11
12
13
14
15
16
17
18
46
76
82
79
75
56
80
65
42
oxides,26 aromatic ethylenes,27 alkynes,28 indole derivatives,29-31
azides and nitriles respectively,32-33 providing the corresponding
cycloaddition products. Some of these new cycloaddition
reactions were used for the synthesis of natural products.29, 30 In
addition, the azaoxyallyl cations were also reported as 2-atom
Et3N
Et3N
Et3N
Et3N
units in [2
+
4]-cycloaddition reactions with N-(2-
chloromethyl)aryl)amides for the construction of 1,4-dihydro-
2H-benzo[d][1,3]oxazines,34 and the intramolecular cycloaddition
involving azaoxyallyl cations for the synthesis of N-Hydroxy
Oxindoles by an aza-nazarov-type reaction was reported by Liao
4
[a] Reaction conditions: 1a (0.5 mmol), 2a (0.375 mmol), base (0.5 mmol), in
solvent (5 mL) were stirred under room temperature.
[b] Yield refers to isolated products after chromatography.
group.35 As
a
relatively stable sulfur source,36-38
With the optimal conditions in hand, we then examined the
scope of the cycloaddition reaction, a set of α-halohydroxamates
1 were tested. As shown in Table 2, α-halohydroxamate
derivatives with various substitution patterns including electron-
deficient and electron-donating groups all carried out this
reaction smoothly to form the corresponding products 3b-3j in
medium to good yields. The yields of 2H-1,4-thiazin-3(4H)-ones
with electron-donating group substituted aromatic ring (3d, 3f,
3g) was slightly higher than the products bearing electron-
deficient aromatic ring (3b-3c, 3e, 3h-3l). There was no
mercaptoacetaldehyde is an electrophilic-nucleophilic reagent
which might function as a cyloadditon partner with 1,3-dipole.
Therefore, We envisioned that thiomorpholin-3-one framework
might be constructed by the [3 + 3]-cycloaddition of azaoxyallyl
cations and mercaptoacetaldehyde. Herein, we wish to report our
preliminary result of the protocol to prepare thiomorpholin-3-one
derivatives: 2H-1,4-thiazin-3(4H)-ones and thiomorpholine-3,5-
diones.
2. Results and Discussion
significant steric effect when
the
ortho-substituted
To investigate the cyclization between azaoxyallyl cations and
mercaptoacetaldehyde, we first examined the reaction between
N-(benzyloxy)-2-chloro-2-phenylacetamide (1a, in situ generated
azaoxyallyl cation) and 1,4-dithiane-2,5-diol (2a, in situ
generated mercaptoacetaldehyde) in the presence of Et3N in THF,
the cycloaddition proceeded smoothly and intermediate 3a’ was
observed, after treated with TsOH in one pot, the desired 4-
(benzyloxy)-2-phenyl-2H-1,4-thiazin-3(4H)-one 3a was isolated
in 79% yield. Subsequently, the conditions of the cyclization
reaction were screened, a series of bases were explored for this
reaction. As shown in Table 1, changing Et3N to DIPEA gave a
lower yield in 57%, while secondary amine DIPA exhibited
almost comparable activity as Et3N and the reaction was
completed in 8h, giving 3a in 71% yield (Table 1, entry 1-3).
The cycloaddition could also be promoted by DMAP, but the
reaction rate became quite slow, with substrate 1a consumed over
96 h and product 3a isolated in 70% yield. DABCO failed to
produce the expected product, giving trace amount of 3a as
indicated by TLC (Table 1, entry 4-5). Inorganic bases such as
K2CO3, Na2CO3, EtONa produced 3a in diminished yields, while
NaOH gave no desired product, accompanied by the totally
decomposation of 1a within 12 h (Table 1, entry 6-9). Then, a
brief solvent survey demonstrated that EA was the best, and the
annulation completed in 8h and produced 3a in 82% yield (Table
1, entry 10-18). Intermediate 3a’ was also successfully isolated
from the reaction, and the diastereoselectivity was checked by
NMR. Unfortunately, all the conditions we tried gave very poor
d.r. value ranging from 1:1 to 1:1.2 (see supplementary data).
arylacetamides were used as starting materials (3b-3d).
Replacing the benzyloxy group on the nitrogen atom with
methoxy or ethoxy group also gave desired products in good
yield (3m, 3n). Disubstituted arylacetamides were also tested to
react with 2a, the corresponding products 3o and 3p were
isolated in 73% and 84% yield, respectively. Finally, N-
(benzyloxy)-2-chloro-2-(naphthalen-2-yl)acetamide
product 3q in 80% yield. It was noteworthy that alkyl group
substituted α-chlorohydroxamate (2-bromo-N-ethoxy-2-
methylpropanamide) was also tested in the reaction, surprisingly,
just the intermediate 3’ was detected in moderate yield, but after
reflux by addition of either TsOH or PCC, trace amount of
product 3 or 4 was detected by TLC.
generated
Table 2. Formation of 2H-1,4-thiazin-3(4H)-ones 3a, b
Table 1. Optimization of the annulation towards 3aa
entry
base
solvent
time (h)
yield (%)b

3
[a] Reaction conditions: 1a (0.5 mmol), 2a (0.375 mmol), Et3N (0.5 mmol),
in EA (5 mL) were stirred under room temperature for 12h, then TsOH (0.1
3. Conclusion
ACCEPTED MANUSCRIPT
mmol) was added and reflux for1h.
In summary, we have described an annulation reaction of α-
halohydroxamates
with
1,4-dithiane-2,5-diol
,
giving
[b] Yield refers to isolated products after chromatography.
thiomorpholin-3-one derivatives in moderate to good yields.
This procedure provided an efficient route to obtain 2H-1,4-
thiazin-3(4H)-ones and thiomorpholine-3,5-diones under mild
condition, exhibiting good functional group tolerance. It is
concerned that azaoxyallyl cations is generated in the reaction
as a crucial intermediate. Further applications of this
methodology in synthetic organic chemistry are currently
underway in our laboratory.
To augment the application of the methodology, oxidation of
the
phenylthiomorpholin-3-one (3a’) was proceeded and 4-
(benzyloxy)-2-phenylthiomorpholine-3,5-dione (4a’) was
intermediate
4-(benzyloxy)-5-hydroxy-2-
isolated as the product to avoid the diastereomer. Then, a variety
of thiomorpholine-3,5-diones were synthesized by the oxidation
of intermediate 5-hydroxythiomorpholin-3-ones (3’) with
pyridinium chlorochromate (PCC) in moderate yields. As shown
in Table 3, a variety of α-halohydroxamate derivatives were
checked in this two-steps reaction. Alkoxy groups on the nitrogen
atom seemed to influence the yield slightly. Benzyloxy, methoxy
and ethoxy group substituted α-halohydroxamate gave desired
thiomorpholine-3,5-diones in 57-67% yield (4a-4c). The
substrates bearing various aromatic groups such as p-flurophenyl,
p-tolyl, o-nitrophenyl, o-methoxyphenyl, naphthyl reacted
smoothly and produced the products in 56-72% yield (4d-4h).
The yields of diones with electron-donating group substituted
aromatic ring seemed to be slightly higher than the electron-
deficient substituted ones (4e, 4g compared to 4d, 4f), indicating
that the azaoxyallyl cations in situ generated from α-
chlorohydroxamates might be stabled by electron-rich aromatic
rings.
Scheme 1. Plausible mechanism
4. Experimental Section
Table 3. Formation of thiomorpholine-3,5-diones 4 a, b
Unless otherwise indicated, all reactions were carried out
without N2/Ar protection with magnetic stirring. Column
chromatography was conducted on silica gel (300−400 mesh)
using compound-appropriate mixtures of n-hexane and EtOAc
1
as eluent. H NMR (400 MHz) and 13C NMR (100 MHz)
spectra were recorded in deuterated solvents and are reported
in ppm relative to tetramethylsilane (TMS).
A variety of α-chlorohydroxamates 1 were synthesized
from the corresponding aldehydes according to the literature.8,
16 All other chemicals were obtained from commercial sources
and used without further purification.
4.1 The Preparation of α-chlorohydroxamates (1)
Aryl aldehyde (10 mmol, 1.0 equiv) and malononitrile (11
mmol, 1.1 equiv) were dissolved in EtOH (10 mL), then
piperidine (1 mmol, 0.1 equiv) was added. The mixture was
stirred at room temperature for 1 h, and the resulting solid was
filtered, washed with cold EtOH, the product 2-
arylidenemalononitrile was collected as a white solid and directly
used in the next step without further purification. Then 2-
arylidenemalononitrile was dissolved in CH2Cl2 (15 mL) and
mCPBA (1.5 equiv) was added in portions, the mixture was
stirred at room temperature overnight. Saturated sodium
bicarbonate solution was added to adjust PH>7, extracted with
CH2Cl2 (15 mL ×3), after washing with brine (15 mL), the
combined organic phase was dried over anhydrous Na2SO4 and
concentrate under reduced pressure to give the oxirane-2,2-
dicarbonitrile as a brown solid, which could be used directly in
the next step without further purification. oxirane-2,2-
dicarbonitrile was then dissolved in CH3CN (15 mL), O-
alkylhydroxylamine hydrochloride (1.2 equiv) was added and the
mixture was heated to reflux for 1 h, H2O (15 mL) was added,
extracted by CH2Cl2 (15 mL ×3), after washing with brine (15
mL), the combined organic phase was dried over anhydrous
Na2SO4 and concentrate under reduced pressure to give the crude
product 2-chloroacetamide as a brown oil, which could be further
purificated by recrystallization or column chromatography on
silica gel (300-400 mesh) to afford the pure product.
[a] Reaction conditions: 1a (0.5 mmol), 2a (0.375 mmol), Et3N (0.5 mmol),
in EA (5 mL) were stirred under room temperature for 12h, after a fast flash
chromography purification of 3’, PCC (0.75 mmol) was added to the solution
of 3’ in DCM and reflux for1h.
[b] Yield refers to isolated products after chromatography.
A plausible mechanism of the annulation is depicted in
Scheme 1. Thus, Under weak basic conditions, α-
halohydroxamate 1 in situ generates azaoxyallyl cation 5, and
meanwhile mercaptoacetaldehyde 2a’ is generated in situ by the
dissociation of 2,5-dihydroxy-1,4-dithiane 2a. Nucleophilic
attack of thiol to azaoxyallyl cation 5 and the following
intramolecular nitrogen anion nucleophilic attack to the aldehyde
group form the product 3’, accomplishing the cycloaddition. The
final product 3 is obtained by dehydration and the product 4 is
obtained by oxidation.

4
Tetrahedron
ACCEPTED MANUSCRIPT
N-(benzyloxy)-2-chloro-2-(3-methoxyphenyl)acetamide
(1d).
4-(Benzyloxy)-2-(2-chlorophenyl)-2H-1,4-thiazin-3(4H)-one (3b).
The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 4/1) as a yellow oil
(1.41 g, 46% over 3 steps), 1H NMR (400 MHz, CDCl3, TMS): δ
= 9.33 (s, 1H), 7.36–7.34 (m, 5H), 7.26–7.23 (m, 1H), 6.96–6.94
(m, 2H), 6.89–6.87 (m, 1H), 5.24 (s, 1H), 4.88 (s, 2H), 3.77 ppm
(s, 3H); 13C NMR (100 MHz, CDCl3, TMS): δ = 165.0, 159.8,
137.2, 134.5, 129.9, 129.5, 129.0, 128.6, 120.0, 115.0, 113.3,
78.3, 58.9, 55.3 ppm.
The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a white solid
(109.5 mg, 66%), m.p. 104–105 oC; H NMR (400 MHz, CDCl3,
1
TMS): δ = 7.49–7.47 (m, 2H), 7.43–7.39 (m, 4H), 7.27–7.22 (m,
3H), 6.42 (d, J = 7.2 Hz, 1H), 5.46 (dd, J1 = 7.6 Hz, J2 = 1.6 Hz,
1H), 5.16–5.09 ppm (m, 3H); 13C NMR (100 MHz, CDCl3,
TMS): δ = 158.9, 134.2, 133.9, 132.6, 130.1, 130.0, 129.6, 129.3,
129.1, 128.7, 127.3, 127.1, 100.5, 78.1, 44.1 ppm; HRMS (EI):
calculated for C17H14ClNO2S, [M+H]+, 332.0507, found
332.0508.
N-(benzyloxy)-2-chloro-2-(4-fluorophenyl)acetamide
(1g).
The title compound was obtained according to the general
procedure described above after recrystallization from n-
hexane/ethyl acetate as white solid (1.53 g, 53% over 3 steps),
m.p. 104–106 C; H NMR (400 MHz, CDCl3, TMS): δ =
9.40 (s, 1H), 7.37–7.32 (m, 7H), 7.01 (t, J = 8.4 Hz, 2H), 5.25
(s, 1H), 4.90 ppm (s, 2H); 13C NMR (100 MHz, CDCl3,
TMS): δ = 164.9, 163.1 (J C–F = 247.3 Hz), 134.5, 131.9 (J C–F
4-(Benzyloxy)-2-(2-nitrophenyl)-2H-1,4-thiazin-3(4H)-one (3c).
The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a pale yellow oil
o
1
1
(123.3 mg, 72%), H NMR (400 MHz, CDCl3, TMS): δ = 8.09–
8.07 (m, 1H), 7.61–7.59 (m, 1H), 7.52–7.47 (m, 3H), 7.41–7.37
(m, 4H), 6.36 (d, J = 7.2 Hz, 1H), 5.54 (s, 1H), 5.51–5.49 (m,
1H), 5.11 ppm (dd, J1 = 18.0 Hz, J2 =10.4 Hz, 2H); 13C NMR
(100 MHz, CDCl3, TMS): δ = 158.4, 148.3, 134.1, 133.5, 130.1,
130.0, 129.9, 129.4, 128.7, 127.5, 125.8, 100.7, 78.2, 43.5 ppm;
HRMS (EI): calculated for C17H14CN2O4S, [M+H]+, 343.0747,
found 343.0750.
= 3.2 Hz), 129.8 (J
(J C–F = 22.0 Hz), 78.3, 58.1 ppm.
= 7.5 Hz), 129.4, 129.1, 128.7, 115.9
C–F
N-(benzyloxy)-2-(4-bromophenyl)-2-chloroacetamide
(1i).
The title compound was obtained according to the general
procedure described above after recrystallization from n-
hexane/ethyl acetate as white solid (1.81 g, 51% over 3 steps),
m.p. 116–118 oC; H NMR (400 MHz, CDCl3, TMS): δ =
4-(Benzyloxy)-2-(2-methoxyphenyl)-2H-1,4-thiazin-3(4H)-one
(3d). The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a yellow oil
1
9.31 (s, 1H), 7.46 (d, J = 8.4 Hz, 2H), 7.37–7.35 (m, 5H), 7.22
(d, J = 8.4 Hz, 2H), 5.22 (s, 1H), 4.90 ppm (s, 2H); 13C NMR
(100 MHz, CDCl3, TMS): δ = 164.5, 134.9, 134.4, 132.0,
129.4, 129.1, 128.7, 123.5, 78.3, 58.2 ppm.
1
(142.4 mg, 87%), H NMR (400 MHz, CDCl3, TMS): δ = 7.49–
7.46 (m, 2H), 7.40–7.37 (m, 3H), 7.31–7.27(m, 1H), 7.14–7.12
(m, 1H), 6.92–6.89 (m, 2H), 6.39 (d, J = 6.4 Hz, 1H), 5.45 (dd, J1
= 7.2 Hz, J2 = 1.2 Hz, 1H), 5.14–5.08 (m, 3H), 3.85 ppm (s, 3H);
13C NMR (100 MHz, CDCl3, TMS): δ = 159.6, 156.5, 134.4,
129.9, 129.7, 129.2, 128.7, 128.3, 126.9, 123.4, 120.6, 110.9,
101.0, 78.0, 55.7, 40.8 ppm; HRMS (EI): calculated for
C18H17NO3S, [M+H]+, 328.1002, found 328.1006.
N-(benzyloxy)-2-chloro-2-(2,3-dimethoxyphenyl)acetamide
(1n). The title compound was obtained according to the
general procedure described above after recrystallization from
n-hexane/ethyl acetate as white solid (1.31 g, 39% over 3
steps), m.p. 92–94 oC; 1H NMR (400 MHz, CDCl3, TMS): δ =
9.27 (s, 1H), 7.36–7.34 (m, 5H), 7.06–6.97 (m, 2H), 6.92–
6.89 (m, 1H), 5.65 (s, 1H), 4.92 (s, 2H), 3.87 (s, 3H), 3.84
ppm (s, 3H); 13C NMR (100 MHz, CDCl3, TMS): δ = 165.3,
152.5, 146.5, 134.8, 130.1, 129.4, 128.8, 128.6, 124.5, 120.6,
113.5, 78.2, 61.1, 55.8, 54.1 ppm.
4-(Benzyloxy)-2-(3-chlorophenyl)-2H-1,4-thiazin-3(4H)-one (3e).
The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a yellow oil
4.2 General procedure for the synthesis of 2H-1,4-thiazin-
3(4H)-ones (3).
1
(117.8 mg, 71%), H NMR (400 MHz, CDCl3, TMS): δ = 7.40–
7.39 (m, 1H), 7.37–7.33 (m, 5H),7.32–7.27 (m, 3H), 6.22 (d, J =
7.2 Hz, 1H), 5.45 (dd, J1 = 6.4 Hz, J2 = 1.6 Hz, 1H), 5.07–5.01 (m,
2H), 4.61–4.60 ppm (m, 1H); 13C NMR (100 MHz, CDCl3,
TMS): δ = 158.4, 136.6, 134.6, 134.1, 130.0, 129.2, 128.7, 127.9,
127.4, 126.1, 99.6, 77.9, 47.0 ppm; HRMS (EI): calculated for
C17H14ClNO2S, [M+H]+, 332.0507, found 332.0503.
Et3N (69 ꢀL, 0.2 mmol, 1.0 equiv) was added to the mixture of 2-
chloroacetamides 1 (0.5 mmol, 1.0 equiv), 1,4-dithiane-2,5-diol
2a (57 mg, 0.375 mmol, 0.75 equiv) in EtOAc (5 mL). The
mixture was stirred at room temperature until complete
consumption of 2-chloroacetamides 1, TsOH·H2O (19 mg, 0.1
mmol, 0.2 equiv) was added, and the mixture was heated to
reflux for 1 h, H2O (5 mL) was added after the mixture was
cooled to room temperature, extracted with EtOAc (5 mL ×3).
After washing with brine (5 mL), the combined organic phase
was dried over anhydrous Na2SO4 and concentrate under reduced
pressure. The residue was purified by column chromatography on
4-(Benzyloxy)-2-(3-methoxyphenyl)-2H-1,4-thiazin-3(4H)-one
(3f). The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a yellow oil
1
(129.3 mg, 79%), H NMR (400 MHz, CDCl3, TMS): δ = 7.36–
7.31 (m, 5H), 7.28–7.24 (m, 1H), 7.00–6.96 (m, 2H), 6.87–6.85
(m, 1H), 6.21 (d, J = 7.2 Hz, 1H), 5.44 (dd, J1 = 7.2 Hz, J2 = 1.6
Hz, 1H), 5.03 (s, 2H), 4.62 (d, J = 1.6 Hz, 1H), 3.79 ppm (s, 3H);
13C NMR (100 MHz, CDCl3, TMS): δ = 159.8, 158.8, 136.1,
134.2, 130.0, 129.7, 129.1, 128.6, 127.3, 120.1, 113.8, 113.5,
99.8, 77.8, 55.3, 47.4 ppm; HRMS (EI): calculated for
C18H17NO3S, [M+H]+, 328.1002, found 328.1007.
silica gel (300−400 mesh) to afford compounds 3.
4-(Benzyloxy)-2-phenyl-2H-1,4-thiazin-3(4H)-one (3a). The title
compound was obtained according to the general procedure
described above after column chromatography on silica gel
(eluting with n-hexane/ EtOAc 5/1) as a pale yellow oil (121.9
mg, 82%), 1H NMR (400 MHz, CDCl3, TMS): δ = 7.41–7.32 (m,
10H), 6.21 (d, J = 7.2 Hz, 1H), 5.44 (dd, J1 = 7.2 Hz, J2 = 2.0 Hz,
1H), 5.04 (s, 2H), 4.65 ppm (d, J = 2.0 Hz, 1H); 13C NMR (100
MHz, CDCl3, TMS): δ = 159.0, 134.6, 134.2, 130.0, 129.2, 128.7,
128.6, 128.4, 127.8, 127.3, 99.9, 77.9, 47.4 ppm; HRMS (EI):
calculated for C17H15NO2S, [M+H]+, 298.0896, found 298.0891.
4-(Benzyloxy)-2-(p-tolyl)-2H-1,4-thiazin-3(4H)-one (3g). The
title compound was obtained according to the general procedure
described above after column chromatography on silica gel
(eluting with n-hexane/ EtOAc 5/1) as a pale yellow oil (133.9

5
mg, 86%), 1H NMR (400 MHz, CDCl3, TMS): δ = 7.37–7.34 (m,
5H), 7.29–7.25 (m, 2H), 7.16 (d, J = 8.0 Hz, 2H), 6.23 (d, J = 7.2
Hz, 1H), 5.45 (dd, J1 = 7.2 Hz, J2 = 1.6 Hz, 1H), 5.05 (s, 2H),
4.62 (d, J = 0.8 Hz, 1H), 2.34 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3, TMS): δ = 159.1, 138.3, 134.2, 131.5, 130.0, 129.4, 129.1,
128.6, 127.7, 127.2, 100.0, 77.9, 47.2, 21.2 ppm; HRMS (EI):
calculated for C18H17NO2S, [M+H]+, 312.1053, found 312.1051.
147.7, 141.6, 133.9, 129.9, 129.3, 129.0, 128.6, 127.6, 123.8,
ACCEPTED MANUSCRIPT
99.5, 78.1, 46.8 ppm; HRMS (EI): calculated for C17H15N2O4S,
[M+H]+, 343.0747, found 343.0745.
4-Methoxy-2-phenyl-2H-1,4-thiazin-3(4H)-one (3m). The title
compound was obtained according to the general procedure
described above after column chromatography on silica gel
(eluting with n-hexane/ EtOAc 5/1) as a pale yellow oil (78.6 mg,
71%), 1H NMR (400 MHz, CDCl3, TMS): δ = 7.42–7.31 (m, 5H),
6.48 (d, J = 7.2 Hz, 1H), 5.63 (dd, J1 = 7.2 Hz, J2 = 1.6 Hz, 1H),
4.65 (d, J = 1.6 Hz, 1H), 3.10 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3, TMS): δ = 158.7, 134.6, 128.7, 128.4, 127.7, 126.1, 101.0,
63.4, 47.3 ppm; HRMS (EI): calculated for C11H11NO2S,
[M+H]+, 222.0583, found 222.0585.
4-(Benzyloxy)-2-(4-fluorophenyl)-2H-1,4-thiazin-3(4H)-one (3h).
The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a yellow oil
1
(118.3 mg, 75%), H NMR (400 MHz, CDCl3, TMS): δ = 7.38–
7.35 (m, 7H), 7.06–7.02 (m, 2H), 6.24 (d, J = 8.0 Hz, 1H), 5.47
(dd, J1 = 7.2 Hz, J2 =1.6 Hz, 1H), 5.07–5.02 (m, 2H), 4.63 ppm (d,
J = 0.8 Hz, 1H); 13C NMR (100 MHz, CDCl3, TMS): δ = 162.7
4-Ethoxy-2-phenyl-2H-1,4-thiazin-3(4H)-one (3n). The title
compound was obtained according to the general procedure
described above after column chromatography on silica gel
(eluting with n-hexane/ EtOAc 5/1) as a pale yellow oil (98.8 mg,
84%), 1H NMR (400 MHz, CDCl3, TMS): δ = 7.41–7.28 (m, 5H),
6.48 (d, J = 7.2 Hz, 1H), 5.58 (dd, J1 = 7.2 Hz, J2 = 1.6 Hz, 1H),
4.64 (d, J = 1.6 Hz, 1H), 4.20–4.09 (m, 2H), 1.31 ppm (t, J = 7.2
Hz, 3H); 13C NMR (100 MHz, CDCl3, TMS): δ = 159.1, 134.7,
128.7, 128.3, 127.7, 127.0, 100.2, 71.7, 47.3, 13.5 ppm; HRMS
(EI): calculated for C11H11NO2S, [M+H]+, 236.0740, found
236.0745.
(J
= 245.9 Hz), 158.9, 134.1, 130.3 (J
= 2.3 Hz), 129.9,
C–F
C–F
129.7 (J
= 7.7 Hz), 129.2, 128.7, 127.3, 115.7 (J
= 21.8
C–F
C–F
Hz), 99.9, 77.9, 46.8 ppm; HRMS (EI): calculated for
C17H14FNO2S, [M+H]+, 316.0802, found 316.0806.
4-(Benzyloxy)-2-(4-chlorophenyl)-2H-1,4-thiazin-3(4H)-one (3i).
The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a yellow solid
1
(122.8 mg, 74%), m.p. 76
–
78 oC; H NMR (400 MHz, CDCl3,
TMS): δ = 7.37–7.32 (m, 9H), 6.23 (d, J = 7.2 Hz, 1H), 5.44 (dd,
J1 = 7.2 Hz, J2 = 2.0 Hz, 1H), 5.06–5.01 (m, 2H), 4.61 ppm (d, J
= 1.6 Hz, 1H); 13C NMR (100 MHz, CDCl3, TMS): δ = 157.5,
133.3, 133.0, 131.9, 128.8, 128.2, 128.1, 127.8, 127.6, 126.3,
98.6, 76.8, 45.7 ppm; HRMS (EI): calculated for C17H14ClNO2S,
[M+H]+, 332.0507, found 332.0501.
4-(Benzyloxy)-2-(2,4-dichlorophenyl)-2H-1,4-thiazin-3(4H)-one
(3o). The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a white solid
1
(133.3 mg, 73%), m.p. 118–120 oC; H NMR (400 MHz, CDCl3,
TMS): δ = 7.48–7.44 (m, 3H), 7.41–7.39 (m, 3H), 7.23 (dd, J1 =
8.4 Hz, J2 = 1.6 Hz, 1H), 7.15 (d, J = 8.4 Hz, 1H), 6.42 (d, J = 7.2
Hz, 1H), 5.47 (dd, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H), 5.11 (dd, J1 =
12.0 Hz, J2 = 6.4 Hz, 2H), 5.04 pm (d, J = 1.2 Hz, 1H); 13C NMR
(100 MHz, CDCl3, TMS): δ = 158.5, 134.9, 134.6, 134.0, 131.1,
130.0, 129.9, 129.8, 129.3, 128.7, 127.3, 100.4, 78.1, 43.5 ppm;
HRMS (EI): calculated for C17H14Cl2NO2S, [M+H]+, 366.0117,
found 366.0119.
4-(Benzyloxy)-2-(4-bromophenyl)-2H-1,4-thiazin-3(4H)-one (3j).
The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a yellow solid
1
(127.9 mg, 68%), m.p. 63
–
65 oC; H NMR (400 MHz, CDCl3,
TMS): δ = 7.49–7.47 (m, 2H), 7.38–7.32 (m, 5H), 7.28–7.26 (m,
2H), 6.23 (d, J = 7.6 Hz, 1H), 5.45 (dd, J1 = 7.2 Hz, J2 =1.6 Hz,
1H), 5.07–5.01 (m, 2H), 4.60 ppm (d, J = 1.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3, TMS): δ = 158.5, 134.1, 133.5, 131.8, 130.0,
129.6, 129.2, 128.7, 127.4, 122.6, 99.9, 77.9, 46.9 ppm; HRMS
(EI): calculated for C17H14BrNO2S, [M+H]+, 376.0001, found
376.0007.
4-(Benzyloxy)-2-(2,3-dimethoxyphenyl)-2H-1,4-thiazin-3(4H)-
one (3p). The title compound was obtained according to the
general procedure described above after column chromatography
on silica gel (eluting with n-hexane/ EtOAc 5/1) as a pale yellow
1
oil (155.5 mg, 87%), H NMR (400 MHz, CDCl3, TMS): δ =
4-(4-(benzyloxy)-3-oxo-3,4-dihydro-2H-1,4-thiazin-2-
7.48–7.46 (m, 2H), 7.40–7.37 (m, 3H), 7.03 (t, J = 8.0 Hz, 1H),
6.91–6.88 (m, 1H), 6.86–6.83 (m, 1H), 6.38 (d, J = 6.8 Hz, 1H),
5.50 (dd, J1 = 7.2 Hz, J2 = 1.2 Hz, 1H), 5.11 (d, J = 1.2 Hz, 1H),
5.10 (s, 2H), 3.90 (s, 3H), 3.86 ppm (s, 3H); 13C NMR (100 MHz,
CDCl3, TMS): δ = 159.9, 152.6, 146.8, 134.4, 130.0, 129.2, 128.6,
127.0, 124.1, 120.5, 112.8, 100.9, 78.0, 61.2, 55.8, 41.1 ppm;
HRMS (EI): calculated for C17H14Cl2NO2S, [M+H]+, 358.1108,
found 358.1123.
yl)benzonitrile (3k). The title compound was obtained according
to the general procedure described above after column
chromatography on silica gel (eluting with n-hexane/ EtOAc 5/1)
o
1
as a white solid (122.5 mg, 76%), m.p. 130–132 C; H NMR
(400 MHz, CDCl3, TMS): δ = 7.65 (d, J = 8.0 Hz, 2H), 7.51 (d, J
= 8.4 Hz, 2H), 7.39–7.36 (m, 5H), 6.28 (d, J = 7.2 Hz, 1H), 5.47
(dd, J1 = 7.2 Hz, J2 = 1.6 Hz, 1H), 5.07 (dd, J1 = 14.0 Hz, J2 = 2.4
Hz, 2H), 4.87 ppm; 13C NMR (100 MHz, CDCl3, TMS): δ =
158.0, 139.7, 133.9, 132.4, 129.9, 129.3, 128.7, 128.6, 127.6,
118.4, 112.3, 99.4, 78.0, 47.1 ppm; HRMS (EI): calculated for
C18H15N2O2S, [M+H]+, 323.0849, found 323.0853.
4-(Benzyloxy)-2-(naphthalen-1-yl)-2H-1,4-thiazin-3(4H)-one
(3q). The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a white solid
(139.0 mg, 80%), m.p. 140–141 oC; 1H NMR (400 MHz, CDCl3,
TMS): δ = 8.07 (d, J = 8.4 Hz, 1H), 7.88–7.80 (m, 2H), 7.59–
7.48 (m, 2H), 7.44–7.24 (m, 7H), 6.41 (d, J = 7.6 Hz, 1H), 5.47
(dd, J1 = 7.2 Hz, J2 =1.6 Hz, 1H), 5.38 (s, 1H), 5.12 ppm (dd, J1 =
18.0 Hz, J2 =10.4 Hz, 2H); 13C NMR (100 MHz, CDCl3, TMS): δ
= 159.4, 134.3, 134.2, 130.6, 130.1, 130.0, 129.4, 129.2, 128.7,
127.1, 126.7, 126.0, 125.8, 125.0, 123.4, 100.7, 78.1, 44.2 ppm;
HRMS (EI): calculated for C21H17NO2S, [M+H]+, 348.1053,
found 348.1050.
4-(benzyloxy)-2-(4-nitrophenyl)-2H-1,4-thiazin-3(4H)-one (3l).
The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a yellow solid
(123.3 mg, 72%), m.p. 138–140 oC; 1H NMR (400 MHz, CDCl3,
TMS): δ = 8.20 (d, J = 8.8 Hz, 2H), 7.57 (d, J = 8.4 Hz, 2H),
7.39–7.34 (m, 5H), 6.30 (d, J = 7.2 Hz, 1H), 5.49 (dd, J1 = 7.2 Hz,
J2 = 1.2 Hz, 1H), 5.07 (dd, J1 = 13.6 Hz, J2 = 10.4 Hz, 2H), 4.72
ppm (s, 1H); 13C NMR (100 MHz, CDCl3, TMS): δ = 158.0,

6
Tetrahedron
4.3 General procedure for the synthesis of
(eluting with n-hexane/ EtOAc 5/1) as a white solid (106.4 mg,
ACCEPTED MANUSCRIPT
thiomorpholine-3,5-diones (4)
.
65%), m.p. 112–114 oC; 1H NMR (400 MHz, CDCl3, TMS): δ =
7.57–7.54 (m, 2H), 7.40–7.38 (m, 3H), 7.21–7.11 (m, 4H), 5.07
(s, 2H), 4.81 (s, 1H), 3.56–3.47 (m, 2H), 2.35 ppm (s, 3H); 13C
NMR (100 MHz, CDCl3, TMS): δ = 166.5, 165.2, 138.8, 133.6,
130.1, 129.8, 129.3, 128.5, 127.7, 78.3, 48.8, 30.9, 21.1 ppm;
HRMS (EI): calculated for C18H17NO3S, [M+H]+, 328.1002,
found 328.1004.
Et3N (69 ꢀL, 0.2 mmol, 1.0 equiv) was added to the mixture of 2-
chloroacetamides 1 (0.5 mmol, 1.0 equiv), 1,4-dithiane-2,5-diol
2a (57 mg, 0.375 mmol, 0.75 equiv) in EtOAc (5 mL). The
mixture was stirred at room temperature until complete
consumption of 2-chloroacetamides 1, solvent was removed
under reduced pressure. The residue was quickly purified by a
short column chromatography on silica gel (300
−
400 mesh,
4-(Benzyloxy)-2-(2-nitrophenyl)thiomorpholine-3,5-dione (4f).
The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a white solid
(100.4 mg, 56%), m.p. 114–116 oC; 1H NMR (400 MHz, CDCl3,
TMS): δ = 8.13 (d, J = 8.0 Hz, 1H), 7.61–7.53 (m, 4H), 7.41–
7.38 (m, 3H), 7.24 (d, J = 7.6 Hz, 1H), 5.76 (s, 1H), 5.08 (dd, J1 =
12.4 Hz, J2 = 9.2 Hz, 2H), 3.81–3.52 ppm (m, 2H); 13C NMR
(100 MHz, CDCl3, TMS): δ = 165.7, 164.6, 148.1, 133.8, 133.5,
130.5, 130.2, 130.0, 129.3, 129.2, 128.5, 126.2, 78.5, 46.2, 32.2
ppm; HRMS (EI): calculated for C17H14N2O5S, [M+H]+,
359.0696, found 359.0691.
eluting with DCM/ EtOAc 5/1) to afford compounds 3’. Then
PCC (162 mg, 0.75 mmol, 1.5 equiv) was added to the solution
of 3’ in DCM (5 ml) and the mixture was heated to reflux until
complete consumption of 3’, H2O (5 mL) was added after the
mixture was cooled to room temperature, extracted with DCM (5
mL ×3). After washing with brine (5 mL), the combined organic
phase was dried over anhydrous Na2SO4 and concentrate under
reduced pressure. The residue was purified by column
chromatography on silica gel (300−400 mesh) to afford
compounds 4.
4-Methoxy-2-phenylthiomorpholine-3,5-dione (4a). The title
compound was obtained according to the general procedure
described above after column chromatography on silica gel
(eluting with n-hexane/ EtOAc 5/1) as a pale yellow solid (67.6
mg, 57%), m.p. 104–106 oC; 1H NMR (400 MHz, CDCl3, TMS):
δ = 7.43–7.26 (m, 5H), 4.87 (s, 1H), 3.94 (s, 3H), 3.55–3.49 ppm
(m, 2H); 13C NMR (100 MHz, CDCl3, TMS): δ = 166.0, 164.9,
133.1, 129.2, 128.9, 127.8, 64.1, 48.8, 30.7 ppm; HRMS (EI):
calculated for C11H11NO3S, [M+H]+, 238.0532, found 238.0538.
4-(Benzyloxy)-2-(2-methoxyphenyl)thiomorpholine-3,5-dione
(4g). The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a pale yellow
solid (123.6 mg, 72%), m.p. 170–172 C; H NMR (400 MHz,
CDCl3, TMS): δ = 7.58–7.55 (m, 2H), 7.40–7.38 (m, 3H), 7.36–
7.31 (m, 1H), 7.01–7.00 (m, 1H), 6.95–6.90 (m, 2H), 5.18 (s, 1H),
5.08 (s, 2H), 3.85 (s, 3H), 3.65–3.56 ppm (m, 2H); 13C NMR
(100 MHz, CDCl3, TMS): δ = 166.8, 165.6, 156.7, 133.8, 130.3,
130.2, 129.2, 128.8, 128.5, 123.0, 120.8, 111.5, 78.3, 55.8, 44.2,
31.6 ppm; HRMS (EI): calculated for C17H14N2O5S, [M+H]+,
344.0951, found 344.0950.
o
1
4-Ethoxy-2-phenylthiomorpholine-3,5-dione (4b). The title
compound was obtained according to the general procedure
described above after column chromatography on silica gel
(eluting with n-hexane/ EtOAc 5/1) as a pale yellow oil (84.2 mg,
67%), 1H NMR (400 MHz, CDCl3, TMS): δ = 7.32–7.28 (m, 5H),
4.80 (s, 1H), 4.05 (q, J = 7.2 Hz, 2H), 3.51–3.40 (m, 2H), 1.30
ppm (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3, TMS): δ =
165.3, 164.2, 132.2, 128.1, 127.8, 126.7, 76.4, 76.0, 75.7, 71.3,
47.8, 29.7, 12.3 ppm; HRMS (EI): calculated for C12H13NO3S,
[M+H]+, 252.0689, found 252.0683.
4-(Benzyloxy)-2-(naphthalen-1-yl)thiomorpholine-3,5-dione (4h).
The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a pale pink solid
(119.9 mg, 66%), m.p. 151–153 oC; 1H NMR (400 MHz, CDCl3,
TMS): δ = 7.91–7.84 (m, 3H), 7.60–7.51 (m, 4H), 7.42–7.38 (m,
3H), 7.36–7.32 (m, 1H), 7.12 (d, J = 6.8 Hz, 1H), 5.54 (s, 1H),
5.15 (s, 2H), 3.61–3.50 ppm (m, 2H); 13C NMR (100 MHz,
CDCl3, TMS): δ = 166.6, 165.2, 134.4, 133.6, 130.4, 130.2, 130.0,
129.4, 129.3, 128.5, 126.8, 126.3, 125.7, 124.7, 123.2, 78.4, 46.8,
31.2 ppm; HRMS (EI): calculated for C21H17NO3S, [M+H]+,
364.1002, found 364.1003.
4-(Benzyloxy)-2-phenylthiomorpholine-3,5-dione (4c). The title
compound was obtained according to the general procedure
described above after column chromatography on silica gel
(eluting with n-hexane/ EtOAc 5/1) as a pale yellow oil (97.2 mg,
62%), 1H NMR (400 MHz, CDCl3, TMS): δ = 7.56–7.54 (m, 2H),
7.40–7.34 (m, 6H), 7.28–7.25 (m, 2H), 5.07 (s, 2H), 4.84 (s, 1H),
3.56–3.45 ppm (m, 2H); 13C NMR (100 MHz, CDCl3, TMS): δ =
166.4, 165.3, 133.7, 133.3, 130.2, 129.3, 129.2, 128.8, 128.6,
127.9, 78.4, 49.1, 30.9 ppm; HRMS (EI): calculated for
C17H15NO3S, [M+H]+, 252.0689, found 252.0683.
Acknowledgments
We are grateful to the National Natural Science Foundation of
China (Nos. 21702155) and the Natural Science Foundation of
Hubei Province (No. 2016CFB168) for financial support.
4-(Benzyloxy)-2-(4-fluorophenyl)thiomorpholine-3,5-dione (4d).
The title compound was obtained according to the general
procedure described above after column chromatography on
silica gel (eluting with n-hexane/ EtOAc 5/1) as a white solid
(101.1 mg, 61%), m.p. 122–124 oC; 1H NMR (400 MHz, CDCl3,
TMS): δ = 7.56–7.53 (m, 2H), 7.40–7.38 (m, 3H), 7.26–7.22 (m,
2H), 7.07–7.03 (m, 2H), 5.07 (s, 2H), 4.81 (s, 1H), 3.62–3.47
ppm (m, 2H); 13C NMR (100 MHz, CDCl3, TMS): δ = 166.3,
Supplementary data
† Supplementary data associated with this article can be found
in
the
online
version,
at
https://doi.org/10.1016/j.tet.XXXX.XX.XXXX
References and notes
165.0, 162.7 (J
= 247.2 Hz), 133.5, 130.2, 129.8 (J
= 8.8
C–F
C–F
Hz), 129.3, 129.0 (J C–F = 3.9 Hz), 128.5, 116.1 (J C–F = 22.1 Hz),
78.3, 48.5, 31.2 ppm; HRMS (EI): calculated for C17H14FNO3S,
[M+H]+, 332.0751, found 332.0755.
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Hershberger, P.; Gosalia, P.; Milewski, M.; Li, Y. L.; Sugarman,

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ACCEPTED MANUSCRIPT
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An efficient and practical process for the synthesis of 2H-1,4-thiazin-3(4H)-ones and
thiomorpholine-3,5-diones.
This method has the feathers of mild condition (common solvents, without N2/Ar protection), good yield,
simple procedure and wide functional group tolerance.