Decarboxylation of isatoic anhydrides with disulfides: An efficient and general synthesis of S-aryl 2-aminobenzothioate derivatives

Article abstract of DOI:10.1016/j.tet.2013.01.024

The decarboxylation of isatoic anhydrides with disulfides was realized in the presence of sodium dithionite, leading to S-aryl 2-aminobenzothioate derivatives in moderate to excellent yields. Furthermore, the decarboxylation of diphenyldiselenide with isa

Full text of DOI:10.1016/j.tet.2013.01.024

Tetrahedron 69 (2013) 2283e2288
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Decarboxylation of isatoic anhydrides with disulfides: an efficient
and general synthesis of S-aryl 2-aminobenzothioate derivatives
,
Miaochang Liu a, Shaomiao Lin a, Jinchang Ding a b, Wenxia Gao a, Huayue Wu a,
,
Jiuxi Chen a
*
a College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, PR China
b Wenzhou Vocational and Technical College, Wenzhou 325035, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
The decarboxylation of isatoic anhydrides with disulfides was realized in the presence of sodium di-
thionite, leading to S-aryl 2-aminobenzothioate derivatives in moderate to excellent yields. Furthermore,
the decarboxylation of diphenyldiselenide with isatoic anhydrides was also examined. It was noted that
unexpected 2-(dimethylamino)-4H-benzo[d][1,3]thiazin-4-one was obtained using tetramethylthiuram
disulfide as sulfur source.
Received 24 September 2012
Received in revised form 31 December 2012
Accepted 8 January 2013
Available online 21 January 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Decarboxylation
Sodium dithionite
Isatoic anhydrides
Disulfides
S-Aryl 2-aminobenzothioates
1. Introduction
preparations. Besides the drawback of these methodologies are as-
sociated with undesirable side reactions owing to the oxidation of
In synthetic organic chemistry, the impact of organo-sulfur
chemistry has led to a resurgence of interest in this field since
sulfur-containing compounds can serve as important auxiliary
functions in synthetic sequences. Thioesters, an important class of
sulfur-containing compounds, are widely presented in a great
number of biologically active compounds and natural products.1 In
recent years, there are a large amount of reports on the synthesis of
bioactive proteins thioesters by native chemical ligation (NCL).2 In
addition, these compounds have been used as acylation agents in
synthetic chemistry.3 Therefore, considerableeffortshavebeenmade
in the development of efficient strategies for the construction of
thioesters.4 However, the preparation of S-aryl 2-aminobenzothioate
derivatives has been scarcely explored.5 Recently, Temperini and co-
workers developed synthesis of S-aryl 2-aminobenzothioate de-
rivatives by the acylation of the odorous, unstable and highly toxic
thiols.6 However, this method usually suffer from one or more limi-
tations, such as very limited substrate scope7 and long reaction times
(10e24 h). Moreover, the use of highly volatile and unpleasant
smelling free thiols leads to serious environmental, safety problems
and also limits the use of these methods, especially in large-scale
thiols and certain thiols are difficult to prepare. In this vein, de-
veloping anefficientandgeneralmethod for thesynthesisofS-aryl 2-
aminobenzothioates still remain in great demand.
As part of the continuing efforts in our laboratory towards the
development of new methodologies using disulfides as sulfur sour-
ces8 or isatoic anhydrides as reaction partners,9 we herein report
a new strategy for the preparation of S-aryl 2-aminobenzothioates
by the decarboxylation of isatoic anhydrides with disulfides10 un-
der mild conditions (Scheme 1). The present protocol could be
a synthetically alternative route, that is, environmentally friendly,
avoiding the use of odorous thiols.
2. Results and discussion
The reaction between isatoic anhydride (1a) and diphenyl
disulfide (2a) was chosen as a model reaction to screen the optimal
O
O
Na2S2O4
YR
O
R1
R1
+
RYYR
K2CO3, DMSO/H2O
NH
R2
N
O
Y = S or Se
R2
* Corresponding author. Tel./fax: þ8657788368280; e-mail addresses: jiuxichen@
Scheme 1.
wzu.edu.cn, huayuewu@wzu.edu.cn (J. Chen).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.01.024

2284
M. Liu et al. / Tetrahedron 69 (2013) 2283e2288
reaction conditions and the results were listed in Table 1. Our in-
vestigation began with an attempted the model reaction in the
absence of reductant, but no target product was detected (Table 1,
entry 1). The yield of the target product S-phenyl 2-
aminobenzothioate (3aa) was enhanced to some extent when the
reaction was conducted in the presence of reductant (e.g., NaHSO3,
Na2SO3, Na2S2O3$5H2O, Na2S2O5, Na2S2O4 and Rongalite11). Among
these reductants used, the reaction afforded 3aa in the highest
yield using Na2S2O4 (65% yield, Table 1, entry 4). It is noteworthy
that the model reaction gave 3aa in 46% yield accompanied by the
formation of 1,2-dihydrobenzo[d][1,3]thiazin-4-one (4)12 in the
presence of Rongalite (Fig. 1).
Fig. 1. X-ray analysis of compound 4.
Table 1
Screening for optimal reaction conditionsa
Table 2
Decarboxylation of isatoic anhydrides with diaryl disulfidesa
O
O
O
O
promoter
SPh
NH2
3aa
O
+
PhSSPh
Na2S2O4
K2CO3, DMSO/H2O
SR
base, solvent
O
R1
R1
+
RSSR
N
H
O
NH
N
O
1a
2a
R2
3
R2
1
2
Entry
Reductant (equiv)
Solvent
Base
Yieldb (%)
Entry Isatoic anhydride Disulfide
Time (min) Product Yieldb (%)
1
2
3
4
5
6
7
8
d
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
CH3CN
CH2Cl2
NMPc
THF
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
NaOH
NaHCO3
Et3N
0
Na2SO3 (3)
NaHSO3 (3)
Trace
Trace
65
47
21
46
36
47
70
76
73
26
0
76
0
32
O
O
Na2S2O4 (3)
Na2S2O5 (3)
Na2S2O3$5H2O (3)
Rongalite (3)
Na2S2O4 (1.5)
Na2S2O4 (2.5)
Na2S2O4 (3.5)
Na2S2O4 (4.5)
Na2S2O4 (5.5)
Na2S2O4 (4.5)
Na2S2O4 (4.5)
Na2S2O4 (4.5)
Na2S2O4 (4.5)
Na2S2O4 (4.5)
Na2S2O4 (4.5)
Na2S2O4 (4.5)
Na2S2O4 (4.5)
Na2S2O4 (4.5)
Na2S2O4 (4.5)
Na2S2O4 (4.5)
Na2S2O4 (4.5)
Na2S2O4 (4.5)
1
2
Ph 2a
30
30
3aa
3ab
86
87
N
H
O
O
1a
1a
O
O
O
O
O
O
O
O
O
p-(Me)C6H4 2b
9
N
H
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
O
3
4
5
6
7
8
9
p-(OMe)C6H4 2c
p-(F)C6H4 2d
p-(Cl)C6H4 2e
p-(Br)C6H4 2f
Ph 2a
30
45
45
45
30
30
30
3ac
3ad
3ae
3af
91
80
85
82
87
87
89
N
H
O
O
O
O
O
O
O
1a
1a
1a
1a
1b
1b
1b
HMPAd
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
O
81
75
53
45
51
64
0
N
H
O
K3PO4
Cs2CO3
d
N
H
K2CO3
86,e 80,f 65g
a
Reaction conditions: 1a (0.6 mmol), 2a (0.2 mmol), base (0.6 mmol), reductant
loading based on 2a, undried solvent (2 mL) 50 ꢀC, 30 min.
O
b
Isolated yield.
N
H
c
NMP¼N-methyl-2-pyrrolidone.
d
HMPA¼hexamethyl phosphoryl triamide.
e
At 60 ꢀC.
O
N
f
At 70 ꢀC.
3ba
3bb
3bc
g
At 80 ꢀC.
O
N
Increasing the amount of Na2S2O4 to 4.5 equiv resulted in 76%
yield (Table 1, entries 8e12). Subsequently, we studied the solvent
effect and found that DMSO was superior to other solvents in-
cluding DMF, CH3CN, CH2Cl2, NMP, THF and HMPA (Table 1, entries
13e17). Screening revealed that the use of K2CO3 as base achieved
the best result (Table 1, entries 18e23).
No target product was detected in the absence of base (Table 1,
entry 24). After a series of trial experiments, we were delighted to
find that the yield could be improved to 81% when the combination
of K2CO3 and DMSO was employed (Table 1, entry 18). Finally, the
reaction temperature was also examined. The results showed that
reaction at 60 ꢀC was most efficient (86% yield, Table 1, entry 25).
Having the optimized reaction conditions in hand, we next ex-
plored the scope and generality of decarboxylation of isatoic an-
hydrides with disulfides. As shown in Table 2, a series of aromatic
p-(Me)C6H4 2b
p-(OMe)C6H4 2c
O
N
O
N
O
O
10
11
p-(Cl)C6H4 2e
45
45
3be
3ca
75
81
O
O
1b
1c
O
Ph 2a
N
H

M. Liu et al. / Tetrahedron 69 (2013) 2283e2288
2285
Table 2 (continued )
5-nitroisatoic anhydride (1f), achieved the corresponding desired
products 3fa and 3fb in slightly lower yields (Table 2, entries
20e21).
Unexpectedly, treatment of 4-fluoroisatoic anhydride (1g) with
1,2-dip-tolyldisulfane (2b) under the optimized conditions afforded
substitution product 4-(p-tolylthio)isatoic anhydride (1h) in 73%
yield, accompanied by a trace amount of S-p-tolyl 2-amino-4-(p-
tolylthio)benzothioate (3hb). As expected, 3hb was isolated in 75%
yield when 1h was used as substrate under the optimized condi-
tions (Scheme 2).
Entry Isatoic anhydride Disulfide
Time (min) Product Yieldb (%)
O
O
12
13
14
15
16
p-(Me)C6H4 2b
45
45
75
75
3cb
3cc
3da
3db
3dc
83
84
76
79
81
N
H
O
1c
O
O
O
p-(OMe)C6H4 2c
N
H
O
O
1c
Ph 2a
Cl
Cl
Cl
N
H
O 1d
O 1d
O 1d
O
O
O
p-(Me)C6H4 2b
N
H
Scheme 2. Reaction of 1g with 2b.
O
p-(OMe)C6H4 (2c) 75
N
H
Moreover, it is worth noting that aliphatic disulfides, such as
dibenzyl disulfide (2g) was still good partner for this trans-
formation, affording the corresponding products 3ag, 3bg and 3dg
in 87%, 83% and 76% yields, respectively (Scheme 3).
O
O
O
17
18
19
20
p-(Cl)C6H4 2e
p-(Br)C6H4 2f
p-(Me)C6H4 2b
Ph 2a
90
90
45
45
45
3de
3df
3eb
3fa
3fb
71
68
63
54
57
Cl
Cl
N
H
O 1d
O 1d
O
O
O
Na2S2O4
K2CO3, DMSO
O
S
Ph
S
Ph
O
R1
R1
+
Ph
S
N
H
N
R2
1
O
NH
R2
3
F
O
2g
O
N
H
O 1e
O
O
S
Ph
S
Ph
S
Ph
NH
3bg (83%)
NH2
3ag (87%)
Cl
NH2
3dg (48%, 76%c)
a Reaction conditions:
1
(0.6 mmol), 2g (0.2 mmol), Na2S2O4 (0.9 mmol) and
DMSO (2 mL), 60 oC, 30 min.
b Isolated yields were given in parenthesis.
c For 75 min.
21
p-(Me)C6H4 2b
a
Reaction conditions: 1 (0.6 mmol), 2 (0.2 mmol), K2CO3 (0.6 mmol), Na2S2O4
Scheme 3. Reaction of isatoic anhydrides with dibenzyl disulfide.
(0.9 mmol) and DMSO (2 mL) 60 ꢀC.
b
Isolated yield.
To extend the scope of this reaction, decarboxylation of isatoic
anhydride (1a) with diphenyldiselenide (2h) as a representative
example is shown in Scheme 4. Under the standard conditions, the
corresponding Se-phenyl 2-aminobenzoselenoate (3ah) was ob-
tained in 73% yield.
disulfides bearing either electron-donating or electron-
withdrawing groups on the aromatic ring were examined (Table
2, entries 1e6). The electronic properties of the groups on the
phenyl ring of aromatic disulfides affected the yields of the reaction
to some extent. Generally, the aromatic disulfides bearing electron-
donating groups (Table 2, entries 2 and 3) produced the corre-
sponding products in slightly higher yields than those analogues
bearing electron-withdrawing groups (Table 2, entries 4e6). On the
other hand, N-substituted isatoic anhydrides, such as N-methyl-
isatoic anhydride (1b), delivered the corresponding 3ba, 3bb, 3bc
and 3be in 87%, 87%, 89% and 75% yields, respectively (Table 2,
entries 7e10).
O
O
Na2S2O4, K2CO3
DMSO, 60 oC, 1h
SePh
NH2
3ah
O
+
PhSeSePh
N
H
O
73 % yield
1a
2h
Scheme 4. Decarboxylation of 1a with diphenyldiselenide.
Next, the decarboxylative reactions of aromatic disulfides with
several benzo-substituted isatoic anhydrides were investigated. As
expected, the groups on the phenyl ring of isatoic anhydrides, such
as methyl, chloro, nitro and fluoro, were compatible under the
optimized reaction conditions. Benzo-substituted isatoic anhy-
drides possessing electron-donating (Table 2, entries 11e13) and
electron-withdrawing (Table 2, entries 14e19) groups on the phe-
nyl ring provided the corresponding S-aryl 2-aminobenzothioates
in moderate to good yields (Table 2, entries 11e19). However,
benzo-substituted isatoic anhydride containing a strong electron-
withdrawing group (eNO2) on the benzene ring, such as
Interestingly, trace yield of 2-(dimethylamino)-4H-benzo[d]
[1,3]thiazin-4-one (3ai) was detected by GC/MS analysis when
tetramethylthiuram disulfide (2i) was used under the standard
conditions. However, we further adjusted reaction parameters and
found that the yield of 3ai was improved to 64% at 100 ꢀC in DMSO
in the absence of reductant and base (Scheme 5).
According to the above observations, a tentative mechanism for
the formation of S-aryl 2-aminobenzothioates was proposed based
on the previous proposed mechanism in Scheme 6. Na2S2O4 can be

2286
M. Liu et al. / Tetrahedron 69 (2013) 2283e2288
O
analysis, the reaction mixture washed with brine and extracted
with ethyl acetate. The organic phase was separated and dried over
anhydrous magnesium sulfate and filtered. The filtrate was con-
centrated and the resulting residue was purified by column chro-
matography on silica gel (300e400 mesh) with petroleum
ethereEtOAc as eluent to provide the desired product.
O
S
DMSO
S
O
S
N
100 oC, 3 h
64% yield
N
S
N
N
N
H
O
S
2i
3ai
1a
Scheme 5. Reaction of 1a with tetramethylthiuram disulfide.
4.2.1. S-4-Methoxyphenyl 2-aminobenzothioate (3ac). Solid; mp
75e76 ꢀC. 1H NMR (500 MHz, CDCl3):
d
¼3.84 (s, 3H), 5.81 (s, 2H),
6.63e8.00 (m, 8H). 13C NMR (125 MHz, CDCl3):
d
¼55.3, 114.8, 116.3,
readily decomposed into radical anion intermediates A. The sul-
furesulfur bond in disulfides 2 is cleaved by the generated from
Na2S2O4, to generate intermediate anion B or radical C. Thus, in-
termediate anion B or radical C could be converted to intermediate
D by nucleophilic attack of the sulfur to carbonyl group in isatoic
anhydride 1. Finally, unstable intermediate D would result in the
liberation of carbon dioxide and the formation of the corresponding
S-aryl 2-aminobenzothioates 3.
117.0, 117.4, 118.3, 130.1, 134.6, 137.1, 148.4, 160.7, 192.3. IR (KBr):
3007 (NH), 1716 (C]O) cmꢁ1. MS (EI, 70 eV): m/z (%)¼259 (Mþ, 9),
120 (100), 92 (23), 65 (16). Anal. Calcd for C14H13NO2S: C, 64.84; H,
5.05. Found: C, 64.81; H, 5.06.
4.2.2. S-4-Fluorophenyl 2-aminobenzothioate (3ad). Solid; mp
103e104 ꢀC. 1H NMR (500 MHz, CDCl3):
d
¼5.81 (s, 2H), 6.65e6.73
Na2S2O4
O
RS
(B)
O
RSSR
2
O
[O]
SR
SR
COOH
CO2
H2O
R1
R1
O
2SO2
(A)
S2O4
R1
+
or
NH
R2
N
N
R2
1
O
R2
2-
3
RS
(C)
(D)
Scheme 6. A tentative mechanism for the formation of S-aryl 2-aminobenzothioates 3.
3. Conclusion
(m, 2H), 7.14e7.99 (m, 6H). 13C NMR (125 MHz, CDCl3):
d¼116.3,
2
116.5 (d, JCF¼22.3 Hz, 1C), 117.1, 117.2, 123.1, 130.1, 134.8, 137.6 (d,
3JCF¼8.0 Hz, 1C), 148.5, 163.5 (d, 1JCF¼246.6 Hz, 1C), 191.2. IR (KBr):
3004 (NH), 1716 (C]O) cmꢁ1. MS (EI, 70 eV): m/z (%)¼247 (Mþ, 7),
120 (100), 92 (66), 65 (17), 108 (17), 58 (16). Anal. Calcd for
C13H10FNOS: C, 63.14; H, 4.08. Found: C, 63.17; H, 4.11.
In summary, we have developed an efficient and general method
for the synthesis of S-aryl 2-aminobenzothioates bydecarboxylation
of isatoic anhydrides with disulfides. The decarboxylation of
diphenyldiselenide with isatoic anhydrides was also conducted
smoothly to afford Se-phenyl 2-aminobenzoselenoate under the
standard conditions. It is worth noting that unexpected 2-(dime-
thylamino)-4H-benzo[d][1,3]thiazin-4-one was obtained when
tetramethylthiuram disulfide was used as sulfur source. Further ef-
forts to expand the scope of the chemistry are currently underway in
our laboratories.
4.2.3. S-p-Tolyl 2-(methylamino)benzothioate (3bb). Solid; mp
114e115 ꢀC. 1H NMR (500 MHz, CDCl3):
d
¼2.33 (s, 2H), 2.76 (d,
J¼5.1 Hz, 2H), 6.56e6.61 (m, 2H), 7.18e7.31 (m, 5H), 7.79 (s, 1H),
7.96 (dd, J¼8.1 Hz, 1H). 13C NMR (125 MHz, CDCl3):
¼21.3, 30.8,
d
111.2,114.4,116.8,124.5,129.9,130.7,135.2,135.6,139.6,150.2,192.0.
IR (KBr): 2923 (NH), 1635 (C]O) cmꢁ1. MS (EI, 70 eV): m/z (%)¼257
(Mþ,16), 134 (100), 116 (13), 91 (10), 77 (20). Anal. Calcd for
C15H15NOS: C, 70.01; H, 5.87. Found: C, 70.04; H, 5.82.
4. Experimental section
4.1. General
4.2.4. S-4-Methoxyphenyl 2-(methylamino)benzothioate (3bc). Solid;
Chemicals and solvents were either purchased or purified by
standard techniques. Melting points were uncorrected and recor-
ded on Digital Melting Point Apparatus WRS-1B. IR spectra were
recorded on an AVATAR 370 FI-Infrared Spectrophotometer. NMR
spectroscopy was performed on both a Bruck spectrometer oper-
ating at 500 MHz (1H NMR) and 125 MHz (13C NMR). TMS (tetra-
methylsilane) was used as an internal standard and CDCl3 was used
as the solvent. Mass spectrometric analysis was performed on
GCeMS analysis (SHIMADZU GC/MS-QP2010). Elemental analysis
was determined on a Carlo-Erba 1108 instrument. Column chro-
matography was performed using EM Silica gel 60 (300e400 mesh).
mp 86e87 ꢀC. 1H NMR (500 MHz, CDCl3):
d
¼2.84 (s, 3H), 3.84 (s, 3H),
6.64e7.41 (m, 7H), 7.88 (s, 1H), 8.03 (d, J¼7.5 Hz, 1H). 13C NMR
(125 MHz, CDCl3):
d
¼29.3, 55.3, 111.2, 114.4, 114.8, 116.7, 118.6, 130.6,
135.2,137.2,150.1,160.6,192.5. IR (KBr): 3010 (NH),1716 (C]O) cmꢁ1
.
MS (EI, 70 eV): m/z (%)¼273 (Mþ, 16), 134 (100), 116 (13), 77 (17).
Anal. Calcd for C15H15NO2S: C, 65.91; H, 5.53. Found: C, 65.95; H, 5.56.
4.2.5. S-4-Chlorophenyl 2-(methylamino)benzothioate (3be). Oil. 1H
NMR (500 MHz, CDCl3):
d
¼2.04 (s, 3H), 6.66e6.70 (m, 2H), 7.41e7.44
(m, 5H), 7.82 (s,1H), 7.99 (d, J¼8.1 Hz,1H).13C NMR (125 MHz, CDCl3):
d¼21.0, 111.3, 114.6, 116.4, 126.6, 129.3, 130.6, 135.5, 136.9, 150.3, 171.1,
190.8. IR (KBr): 3360 (NH),1635 (C]O) cmꢁ1. MS (EI, 70 eV): m/z (%)¼
277 ([Mþ2]þ, 7), 277 (Mþ, 21),134 (100),116 (17), 77 (23). Anal. Calcd
for C14H12ClNOS: C, 60.54; H, 4.35. Found: C, 60.59; H, 4.38.
4.2. General procedure for the synthesis of S-aryl 2-
aminobenzothioates
A mixture of isatoic anhydride 1 (0.6 mmol), disulfide 2
(0.2 mmol), and Na2S2O4 (0.9 mmol) in undried DMSO (2 mL) was
stirred at 60 ꢀC for respective time in Table 2 and Scheme 2. After
the completion of the reaction, as monitored by TLC and GCeMS
4.2.6. S-Phenyl 2-amino-3-methylbenzothioate (3ca). Solid; mp
102e103 ꢀC. 1H NMR (500 MHz, CDCl3):
d
¼2.17 (s, 3H), 5.92 (s, 2H),
6.65e7.52 (m, 7H), 7.93 (d, J¼8 Hz, 1H). 13C NMR (125 MHz, CDCl3):
d¼22.6, 115.7, 123.4, 128.2, 129.1, 129.4, 135.3, 135.6, 147.0, 191.8. IR

M. Liu et al. / Tetrahedron 69 (2013) 2283e2288
2287
(KBr): 3360 (NH), 1615 (C]O) cmꢁ1. MS (EI, 70 eV): m/z (%)¼243
(Mþ, 12), 134 (100), 106 (21), 77 (16). Anal. Calcd for C14H13NOS: C,
69.11; H, 5.39. Found: C, 69.15; H, 5.42.
7.18e7.83 (m, 7H). 13C NMR (125 MHz, CDCl3):
d
¼33.0, 111.1, 114.4,
116.4, 117.3, 127.0, 128.5, 128.8, 130.6, 135.0, 137.9, 149.9, 192.3. IR
(KBr): 3360 (NH), 1615 (C]O) cmꢁ1. MS (EI, 70 eV): m/z (%)¼279
([Mþ2]þ, 8), 277 (Mþ, 24), 154 (100), 156 (36), 126 (23), 91 (26).
Anal. Calcd for C14H12ClNOS: C, 60.54; H, 4.35. Found: C, 60.61; H,
4.37.
4.2.7. S-p-Tolyl 2-amino-3-methylbenzothioate (3cb). Solid; mp
111e112 ꢀC. 1H NMR (500 MHz, CDCl3):
d
¼2.16 (s, 3H), 2.41 (s, 3H),
5.92 (s, 2H), 6.41e7.40 (m, 6H), 7.93 (d, J¼8.5 Hz, 1H). 13C NMR
(125 MHz, CDCl3):
d¼21.3, 22.6, 115.7, 117.0, 123.4, 124.5,
4.2.15. Se-Phenyl 2-aminobenzoselenoate (3ah). Oil. 1H NMR
128.2, 130.0, 135.3, 135.6, 139.7, 147.0, 192.3. IR (KBr): 3001 (NH),
1706 (C]O) cmꢁ1. MS (EI, 70 eV): m/z (%)¼257 (Mþ, 7), 134 (100),
106 (18), 77 (14). Anal. Calcd for C15H15NOS: C, 70.01; H, 5.87.
Found: C, 70.06; H, 5.93.
(500 MHz, CDCl3):
d
¼6.47 (s, 2H), 6.74e6.75 (m, 2H), 7.28e8.23 (m,
7H). 13C NMR (125 MHz, CDCl3):
d
¼116.7, 116.7, 126.2, 127.7,
128.6, 129.7, 133.6, 136.4, 146.7, 149.6, 159.2. IR (KBr): 2998 (NH),
1716 (C]O) cmꢁ1. MS (EI, 70 eV): m/z (%)¼276 (Mþ,7), 120 (100),
199 (23), 108 (10), 65 (17). Anal. Calcd for C13H11NOSe: C, 56.53; H,
4.01. Found: C, 56.56; H, 4.05.
4.2.8. S-4-Methoxyphenyl 2-amino-3-methylbenzothioate (3cc). Oil.
1H NMR (500 MHz, CDCl3):
d
¼1.97 (s, 3H), 3.72 (s, 3H), 4.04 (s, 2H),
6.72e7.33 (m, 7H). 13C NMR (125 MHz, CDCl3):
d
¼21.1, 55.5, 114.6,
Acknowledgements
114.7, 119.8, 128.4, 132.4, 132.6, 146.1, 158.3, 159.9, 171.1, 192.4. IR
(KBr): 2959 (NH), 1741 (C]O) cmꢁ1. MS (EI, 70 eV): m/z (%)¼273
(Mþ, 21), 134 (100), 126 (27), 77 (19). Anal. Calcd for C15H15NO2S: C,
65.91; H, 5.53. Found: C, 65.97; H, 5.58.
We thank the National Natural Science Foundation of China
(Nos. 21102105 and 21072153), Science and Technology De-
partment of Zhejiang Province (No. 2011R09002-03) and Natural
Science Foundation of Zhejiang Province (No. LY12B02011) for fi-
nancial support.
4.2.9. S-Phenyl 2-amino-4-chlorobenzothioate (3da). Solid; mp
127.2e127.3 ꢀC. 1H NMR (500 MHz, CDCl3):
d
¼5.81 (s, 2H), 6.61 (d,
J¼8.8 Hz, 1H), 7.23e7.50 (m, 6H), 7.97 (s, 1H). 13C NMR (125 MHz,
Supplementary data
CDCl3):
d¼118.1, 118.5, 120.7, 127.3, 129.2, 129.6, 130.2, 134.6, 135.5,
147.0, 190.7. IR (KBr): 3010 (NH), 1716 (C]O) cmꢁ1. MS (EI, 70 eV):
m/z (%)¼263 ([Mþ2]þ, 4), 263(Mþ, 13), 154 (100), 156 (31), 126 (31),
90 (16). Anal. Calcd for C13H10ClNOS: C, 59.20; H, 3.82. Found: C,
59.23; H, 3.86.
Supplementary data related to this article can be found online at
http://dx.doi.org/10.1016/j.tet.2013.01.024.
References and notes
1. (a) Turpin, J. M.; Song, Y.; Inman, J. K.; Huang, M.; Wallqvist, A.; Maynard, A.;
Covell, D. G.; Rice, W. G.; Appella, E. J. Med. Chem. 1999, 42, 67; (b) Shimizu, T.;
Seki, M. Tetrahedron Lett. 2000, 41, 5099; (c) Kalia, J.; Raines, R. T. ChemBioChem
4.2.10. S-p-Tolyl 2-amino-4-chlorobenzothioate (3db). Solid; mp
134e135 ꢀC. 1H NMR (500 MHz, CDCl3):
d
¼2.42 (s, 3H), 5.81 (s, 2H),
6.61e7.98 (m, 7H). 13C NMR (125 MHz, CDCl3):
d
¼21.3, 118.2, 118.5,
€
2006, 7, 1375; (d) Frenzel, T.; Brunjes, M.; Quitschalle, M.; Kirschning, A. Org.
120.7, 123.7, 129.2, 130.1, 134.6, 135.5, 140.0, 146.9, 191.2. IR (KBr):
3362 (NH), 1651 (C]O) cmꢁ1. MS (EI, 70 eV): m/z (%)¼277 ([Mþ2]þ,
6), 277 (Mþ, 19), 154 (100), 156 (32), 126 (27), 90 (14), 99 (13). Anal.
Calcd for C14H12ClNOS: C, 60.54; H, 4.35. Found: C, 60.57; H, 4.38.
Lett. 2006, 8, 135; (e) Neumann, C. S.; Walsh, C. T. J. Am. Chem. Soc. 2008, 130,
14022; (f) Reed, K. A.; Manam, R. R.; Mitchell, S. S.; Xu, J.; Teisan, S.; Chao, T.-H.;
Deyanat-Yazdi, G.; Neuteboom, S. T. C.; Lam, K. S.; Potts, B. C. M. J. Nat. Prod.
2007, 70, 269; (g) Schwarzer, D.; Ludwig, C.; Thiel, I. V.; Mootz, H. D. Bio-
chemistry 2012, 51, 233.
2. (a) Dawson, P. E.; Muir, T. W.; Clark-Lewis, I.; Kent, S. B. Science 1994, 266, 776;
(b) Nagaike, F.; Onuma, Y.; Kanazawa, C.; Hojo, H.; Ueki, A.; Nakahara, Y.;
Nakahara, Y. Org. Lett. 2006, 8, 4465; (c) Kang, J.; Richardson, J. P.; Macmillan,
D. Chem. Commun. 2009, 407; (d) Kang, J.; Reynolds, N. L.; Tyrrell, C.; Dorin, J.
R.; Macmillan, D. Org. Biomol. Chem. 2009, 7, 4918; (e) Kang, J.; Macmillan, D.
Org. Biomol. Chem. 2010, 8, 1993; (f) Dheur, J.; Ollivier, N.; Melnyk, O. Org. Lett.
2011, 13, 1560; (g) Hou, W.; Zhang, X.; Li, F.; Liu, C.-F. Org. Lett. 2011, 13, 386.
3. (a) Yost, J. M.; Zhou, G.; Coltart, D. M. Org. Lett. 2006, 8, 1503; (b) Ozaki, S.;
Adachi, M.; Sekiya, S.; Kamikawa, R. J. Org. Chem. 2003, 68, 4586; (c) Mori, Y.;
Seki, M. Organic Syntheses; 2007; Collect Vol. No. 84 p 285; Collect. Vol. No. 11, p
281; (d) Wittenberg, R.; Srogl, J.; Egi, M.; Liebeskind, L. S. Org. Lett. 2003, 5,
3033; (e) Ikeda, Z.; Hirayama, T.; Matsubara, S. Angew. Chem., Int. Ed. 2006, 45,
8200; (f) Villalobos, J. M.; Srogl, J.; Liebeskind, L. S. J. Am. Chem. Soc. 2007, 129,
15734.
4. For selected recent examples, see: (a) Ranu, B. C.; Jana, R. Adv. Synth. Catal. 2005,
347, 1811; (b) Iranpoor, N.; Firouzabadi, H.; Khalili, D.; Motevalli, S. J. Org. Chem.
2008, 73, 4882; (c) Katritzky, A. R.; Shestopalov, A. A.; Suzuki, K. Synthesis 2004,
1806; (d) Zhang, L.; Luo, Y.; Fan, R. H.; Wu, J. Green Chem. 2007, 9, 1022; (e)
Chakraborti, A.; Shivani, K. J. Org. Chem. 2006, 71, 5785; (f) Cao, H.; McNamee, L.;
Alper, H. J. Org. Chem. 2008, 73, 3530; (g) Kim, S.; Kim, S.; Otsuka, N.; Ryu, I. Angew.
Chem., Int. Ed. 2005, 44, 6183; (h) Basu, B.; Paul, S.; Nanda, A. K. Green Chem. 2010,
12, 767; (i) Sawada, N.; Itoh, T.; Yasuda, N. Tetrahedron Lett. 2006, 47, 6595; (j)
Arisawa, M.; Yamada, T.; Yamaguchi, M. Tetrahedron Lett. 2010, 51, 6090; (k)
Narayanaperumal, S.; Alberto, E. E.; Gul, K.; Kawasoko, C. Y.; Dornelles, L.;
Rodrigues, O. E. D.; Braga, A. L. Tetrahedron 2011, 67, 4723; (l) Das, R.; Chakraborty,
D. Synthesis 2011, 1621.
4.2.11. S-4-Methoxyphenyl 2-amino-4-chlorobenzothioate
(3dc). Solid; mp 91e92 ꢀC. 1H NMR (500 MHz, CDCl3):
d
¼2.04 (s,
3H), 6.81e6.85 (m, 5H), 7.38 (s, 2H), 7.39e7.41 (m, 2H). 13C NMR
(125 MHz, CDCl3):
d
¼55.3, 114.6, 114.9, 115.8, 128.4, 128.8, 132.6,
134.1, 137.0, 159.9, 171.1, 192.6. IR (KBr): 3345 (NH), 1640 (C]O)
cmꢁ1. MS (EI, 70 eV): m/z (%)¼295 ([Mþ2]þ, 6), 293 (Mþ, 17), 154
(100), 156 (28), 126 (27), 90 (12), 77 (9). Anal. Calcd for
C14H12ClNO2S: C, 57.24; H, 4.12. Found: C, 57.27; H, 4.17.
4.2.12. S-4-Chlorophenyl 2-amino-4-chlorobenzothioate (3de). Solid;
mp 107e108 ꢀC. 1H NMR (500 MHz, CDCl3):
d
¼5.82 (s, 2H),
6.66e7.43 (m, 6H), 7.97 (dd, J¼8.1 Hz, 1H). 13C NMR (125 MHz,
CDCl3):
d¼116.3, 117.1, 126.3, 129.3, 130.1, 134.8, 135.8, 136.8, 148.6,
171.1, 190.6. IR (KBr): 3330 (NH), 1630 (C]O) cmꢁ1. MS (EI, 70 eV):
m/z (%)¼299 ([Mþ2]þ, 9), 297 (Mþ, 24),154 (100),156 (32),126 (30),
99 (17), 90 (15). Anal. Calcd for C13H9Cl2NOS: C, 52.36; H, 3.04.
Found: C, 52.41; H, 3.08.
4.2.13. S-4-Bromophenyl 2-amino-4-chlorobenzothioate (3df). Oil.
5. (a) De Champlain, P.; Luche, J. L.; Marty, R. A.; De Mayo, P. Can. J. Chem. 1976, 54,
3749; (b) Azab, M. E.; Kassab, E. A.; El-Hashash, M. A.; Ali, R. S. Phosphorus,
Sulfur Silicon Relat. Elem. 2009, 184, 610.
6. Temperini, A.; Annesi, D.; Testaferri, L.; Tiecco, M. Tetrahedron Lett. 2010, 51,
5368.
1H NMR (500 MHz, CDCl3):
d
¼5.83 (s, 2H), 6.23 (d, J¼9 Hz, 1H),
7.24e7.93 (m, 6H). 13C NMR (125 MHz, CDCl3):
d
¼116.2, 117.1, 123.9,
126.9, 130.1, 130.7, 132.2, 135.0, 136.8, 148.6, 190.6. IR (KBr): 3230
(NH), 1646 (C]O) cmꢁ1. MS (EI, 70 eV): m/z (%)¼345 ([Mþ2]þ, 18),
343 (Mþ, 19), 154 (100), 156 (27), 77 (18). Anal. Calcd for
C13H9BrClNOS: C, 45.57; H, 2.65. Found: C, 45.59; H, 2.63.
7. Only one substrate isatoic anhydride was examined, without mentioning of
N-substituted or benzo-substituted isatoic anhydrides.
8. (a) Guo, W. X.; Chen, J. X.; Wu, D. Z.; Ding, J. C.; Chen, F.; Wu, H. Y. Tetrahedron
2009, 65, 5240; (b) Dan, W. X.; Deng, H. J.; Chen, J. X.; Liu, M. C.; Ding, J. C.; Wu,
H. Y. Tetrahedron 2010, 66, 7384; (c) Lin, S. M.; Zhang, J. L.; Chen, J. X.; Gao, W.
X.; Ding, J. C.; Su, W. K.; Wu, H. Y. J. Braz. Chem. Soc. 2010, 21, 1616; (d) Guo, W.
X.; Lv, G. S.; Chen, J. X.; Gao, W. X.; Ding, J. C.; Wu, H. Y. Tetrahedron 2010, 66,
4.2.14. S-Benzyl 2-amino-4-chlorobenzothioate (3dg). Oil. 1H NMR
(500 MHz, CDCl3):
d
¼4.26 (s, 2H), 5.86 (s, 2H), 6.59 (d, J¼8.5 Hz,1H),

2288
M. Liu et al. / Tetrahedron 69 (2013) 2283e2288
2297; (e) Huang, D. Y.; Chen, J. X.; Dan, W. X.; Ding, J. C.; Liu, M. C.; Wu, H. Y.
Adv. Synth. Catal. 2012, 354, 2123.
9. (a) Lu, W.; Chen, J. X.; Liu, M. C.; Ding, J. C.; Gao, W. X.; Wu, H. Y. Org. Lett. 2011,
13, 6114; (b) Chen, J. X.; Wu, D. Z.; Liu, M. C.; Wu, H. Y.; Ding, J. C.; Su, W. K.
Tetrahedron Lett. 2008, 49, 3814; (c) Chen, J. X.; Su, W. K.; Wu, H. Y.; Liu, M. C.;
Jin, C. Green Chem. 2007, 9, 972.
Li, X.; Verpoort, F.; Duan, C. Eur. J. Org. Chem. 2011, 7331; (c) Zhu, R.-H.; Shi, X.-X.
Synth. Commun. 2012, 42, 1108; (d) Firouzabadi, H.; Iranpoor, N.; Jafarpour, M. J.
Sulfur Chem. 2005, 26, 313; (e) Jafarpoura, M.; Rezaeifarda, A.; Heidaria, M.
Phosphorus, Sulfur Silicon Relat. Elem. 2011, 186, 1470.
11. For selected reviews on Rongalite, see: (a) Chen, J. X. Synlett 2012, 157; (b)
Kotha, S.; Khedkar, P. Chem. Rev. 2012, 112, 1650.
10. Preparation of disulfides by the oxidation of thiols is an easy and well known
procedure. However, structurally different thiols are not always available and
sometimes not easy to prepare. For Selected examples of thiols-free, see: (a)
Hase, T. A.; Perakyla, H. Synth. Commun.1982, 12, 947; (b) Li, Y.; Nie, C.; Wang, H.;
12. The structure of compound 4 was unambiguously confirmed by X-ray single-
crystal diffraction analysis. CCDC-898086 contains the supplementary crystal-
lographic data for 4, which is available free of charge via www.ccdc.cam.ac.uk/
data_request/cif