FeF3/i2-catalyzed synthesis of 4-chalcogen- substituted arylamines by direct thiolation of an arene C-H bond

Article abstract of DOI:10.1055/s-0030-1258449

An efficient regioselective synthesis of 4-chalcogen-substituted-arylamines by FeF₃-catalyzed sulfenylation and selenation of arylamines has been developed. In the presence of FeF₃and I₂, a variety of arylamines underwent the reaction with disulfides or diselenides to afford the corresponding 4-sulfenyl-or 4-selenenyl-arylamines in moderate to good yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0030-1258449

PAPER
1099
FeF3/I2-Catalyzed Synthesis of 4-Chalcogen-Substituted Arylamines by Direct
Thiolation of an Arene C–H Bond
F
eF -CatalyzedSu
i
lfenyla
a
tion andSe
o
lenationof
A
-
rylamin
L
e
s
i Fang,a Ri-Yuan Tang,a Xing-Guo Zhang,*a Jin-Heng Li*a,b
3
a
College of Chemistry & Materials Engineering, Wenzhou University, Wenzhou 325035, P. R. of China
Key Laboratory of Chemical Biology & Traditional Chinese Medicine Research (Ministry of Education), Hunan Normal University,
Changsha 410081, P. R. of China
b
Fax +86(731)88872576; E-mail: jhli@hunnu.edu.cn
Received 30 December 2010; revised 30 January 2011
R2
H
Y
Abstract: An efficient regioselective synthesis of 4-chalcogen-
substituted arylamines by FeF3-catalyzed sulfenylation and selena-
tion of arylamines has been developed. In the presence of FeF3 and
I2, a variety of arylamines underwent the reaction with disulfides or
diselenides to afford the corresponding 4-sulfenyl- or 4-selenenyl-
arylamines in moderate to good yields.
FeF3 (20 mol%)
I2 (1 mol%)
R2
R1
R1
Y
R2
Y
(1)
(2)
+
MeCN, 80 °C
N
N
H
H
R2
FeF3 (20 mol%)
I2 (10 mol%)
R2
Y
H
Y
Y
+
Key words: iron, iodine, sulfenylation, selenation, arylamine, 4-
chalcogen-substituted arylamine
R2
MeCN, 80 °C
NHR1
NHR1
Y = S, Se
Scheme 1 Chalcogenation with disulfides or diselenides
Aryl sulfides are a valuable class of compounds that have
been widely used as pharmaceuticals and synthetic inter-
mediates.1 Traditionally, aryl sulfides are prepared by re-
duction of the corresponding sulfones or sulfoxides under
harsh reaction conditions.2 Transition-metal-catalyzed
cross-coupling reactions of thiols with aryl halides3–5 or
aryl triflates6provide another alternative access. However,
these procedures suffer from the oxidative S–S coupling
of thiols and/or catalyst poisoning.7 To overcome these
drawbacks, disulfides are commonly employed to replace
thiols.8
were investigated. We found that treatment of aniline (1a)
with disulfide 2a afforded rather low conversions and
yields using either FeF3 or IPy2BF4 as the catalyst alone
(Table 1, entries 1 and 2). However, the desired product 3
could be obtained in 63% yield with an 11:1 ratio of para-
and ortho-thiolation isomers using 20 mol% FeF3 com-
bined with 10 mol% IPy2BF4 (entry 3). Other iron salts,
such as FeCl3, FeBr3, Fe2(SO4)3, and FeCl2, were also ex-
amined, but they were less effective than FeF3 (entries 4–
7). We found that I2 was a more effective catalyst than
IPy2BF4, enhancing the yield from 63 to 79% (entries 3
and 8). The amount of I2 affected the reaction: a lower
yield was observed when the amount of I2 was increased
to 20 mol% or decreased to 5 mol% (entries 9 and 10).
Among the effects of solvent and reaction temperature ex-
amination, the reaction in MeCN at 80 °C gave the best re-
sults (entries 11–15). Finally, the loading of FeF3 was
evaluated. The results showed that the yield was lowered
to some extent in the presence of 10 mol% FeF3 (entry
16). It is noteworthy that the desired product 3 was formed
in 43% yield in the absence of Fe catalysts (entry 17).
Recently, the direct functionalization of arene C–H bond
has received attention because of its potential low cost and
environmentally benign features.8i,j,9–12 Thus, C–S bond
forming reactions through C–H functionalization of arene
or heteroarene with various sulfur-containing reagents
have been investigated.10 For example, Yadav and co-
workers reported an iron(III) chloride catalyzed direct thi-
olation of indoles with thiols.11 We have also developed
an iodine-promoted iron-catalyzed chalcogenation of
indoles with disulfides or diselenides (Scheme 1,
Equation 1.12 As a continuing interest in the synthetic util-
ity of disulfides,12,13 we sought to extend these catalytic
systems to the thiolation of arylamines. Here, we report an
efficient synthesis of sulfenylarylamines and selenenyl-
arylamines by direct thiolation of an arene C–H bond of
arylamines with disulfides or diselenides using FeF3 and
I2 as co-catalysts (Scheme 1, Equation 2).8i,j
With the optimal reaction conditions in hand, we subse-
quently explored the scope of both amines and disulfides
(Tables 2 and 3). As shown in Table 2, a variety of disul-
fides 2b–g were investigated by treating with aniline (1a)
in the presence of FeF3 and I2. The results showed that nu-
merous diaryl disulfides 2b–f were suitable substrates for
this reaction, giving the corresponding products in moder-
ate to good yields with high regioselectivity (Table 2, en-
tries 1–5). For example, 1,2-di(p-tolyl)disulfide (2b)
reacted with amine 1a, FeF3, and I2 to afford the desired
product 4 in 75% yield with a 97:3 ratio of para/ortho-thi-
olation isomers (entry 1). Disulfide 2e, having an elec-
tron-withdrawing group on the aromatic ring, was also
suitable under the standard conditions (entry 4). Product
The reaction between aniline (1a) and 1,2-diphenyl disul-
fide (2a) was chosen to investigate the optimal reaction
conditions (Table 1). Initially, a series of catalytic systems
SYNTHESIS 2011, No. 7, pp 1099–1105
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x
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Advanced online publication: 24.02.2011
DOI: 10.1055/s-0030-1258449; Art ID: H58110SS
© Georg Thieme Verlag Stuttgart · New York

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X.-L. Fang et al.
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Table 1 Sulfenylation of Aniline (1a) with Diphenyl Disulfide (2a)a
tuted anilines were also investigated. The reaction be-
tween N-methylaniline and diphenyl disulfide (2a)
proceeded smoothly under the standard conditions to af-
ford the corresponding product in 90% yield (entry 9).
However, no product was observed in the reaction of N-
phenylacetamide with diphenyl disulfide (2a) (entry 10),
presumably because of the strong electron-withdrawing
effect of the acyl group.
NH2
SPh
NH2
+
PhSSPh
PhS
NH2
+
2a
1a
3A
3B
Entry [Fe]
Additive
(mol%)
Solvent Conversion Yield
(mol%)
(%)b
(%)c
1
2
3
4
5
6
7
8
9
FeF3 (20)
–
–
MeCN
9
8
Selenylation of aniline (1a) with diselenides 2 was also
tested under the standard reaction conditions (Scheme 2).
In the presence of 20 mol% FeF3 and 10 mol% I2, 1,2-
diphenyl diselenide (2h) underwent the selenylation reac-
tion with aniline (1a) to give the corresponding product in
71% yield. However, dimethyl diselenide (2i) displayed
less reactivity, giving the target product 21 in 23% yield.
IPy2BF4 (10) MeCN 36
IPy2BF4 (10) MeCN 88
IPy2BF4 (10) MeCN 50
IPy2BF4 (10) MeCN 78
16 (4:1)
63 (11:1)
34 (6:1)
trace
FeF3 (20)
FeCl3 (20)
FeBr3 (20)
Fe2(SO4)3 (20) IPy2BF4 (10) MeCN 80
trace
SeR
FeCl2 (20)
FeF3 (20)
FeF3 (20)
IPy2BF4 (10) MeCN 70
56 (7:1)
79 (13:1)
48 (6:1)
61 (10:1)
72 (8:1)
23 (3:1)
18 (7:1)
trace
FeF3, I2
NH2
RSeSeR
RSe
NH2
+
+
NH2
MeCN
I2 (10)
I2 (20)
I2 (5)
MeCN 90
MeCN 82
MeCN 71
80 °C, 36 h
1a
2h R = Ph
2i R = Me
A
B
20 R = Ph 71% (A/B = 80:20)
21 R = Me 23% (A/B = 83:17)
10 FeF3 (20)
11 FeF3 (20)
12 FeF3 (20)
13 FeF3 (20)
14d FeF3 (20)
15e FeF3 (20)
16 FeF3 (10)
Scheme 2 Selenation of aniline (1a) with diselenides (2)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
I2 (10)
DMF
DCE
THF
93
35
30
In light of these above results, a number of arenes were
tested under the standard conditions (Scheme 3). Howev-
er, the reactions of benzene (22a) or phenol (22b) with
1,2-diphenyl disulfide (2a) were unsuccessful in the pres-
ence of FeF3 and I2. To our delight, the electron-rich aro-
matic compounds 22c and 22d were suitable for this
reaction. For example, 1,3,5-trimethoxybenzene (22d)
was reacted with 1,2-diphenyl disulfide (2a) to give the
corresponding product 26 in 90% yield.
MeCN trace
MeCN 95
MeCN 86
MeCN 58
73 (8:1)
72 (10:1)
43 (4:1)
17
–
a Reaction conditions: 1a (0.4 mmol), 2a (0.4 mmol), [Fe], additive
and solvent (3 mL) at 80 °C under N2 atmosphere for 36 h.
b Conversion was determined by GC-MS analysis.
c Isolated yield. Ratio of 3A/3B was determined by GC-MS analysis.
d At r.t.
Ph
FeF3, I2
S
S
SPh
+
MeCN, 80 °C, 36 h
R
R
Ph
22a R = H
22b R = OH
22c R = 1,3,5-(Me)3
22d R = 1,3,5-(MeO)3
2a
23 trace
24 trace
25 55%
26 90%
e At 110 °C.
8, an important medical intermediate,14 was isolated in
45% yield from the reaction between heteroaryl disulfide
2f and aniline (1a) (entry 5). However, the reaction of ali-
phatic dimethyl disulfide (2g) gave the corresponding
product 9 in a low yield (25%, entry 6).
Scheme 3 Sulfenylation of arenes 22 with 1,2-diphenyl disulfide
(2a)
R1SSR1 + I2
R1SI
SR1
SR1
2
C
+
NH2
NH2
Encouraged by these results, we next evaluated the scope
of arylamines for the reaction with diphenyl disulfide (2a)
(Table 3). The results showed that electronic effects of
substituents affected the reaction (Table 3, entries 1–10).
When treated with substrate 2a, anilines bearing an elec-
tron-donating substituent on the aryl moiety, such as
methyl or methoxy, gave the thiolation products in mod-
erate yields and higher regioselectivity (entries 1–6). A
good yield was obtained from the reaction of 1h, which
has both a chloro and a methoxy groups on the aromatic
ring (entry 7). However, a low yield was observed when
2-chloroaniline (1i), bearing an electron-withdrawing
group, was used as a coupling partner (entry 8). N-Substi-
NH2
R2
R2
H+
R1SI
+
D
+
NH2
R2
NH2
I–
1
C
R1S
R2
R1S
H+
R2
E
R1SH
R1SI
C
R1SSR1 + HI
2
+
FeX3
R1SFeX2
R1SI
R1SSR1 + HI
+
+
+
HX
2
C
F
R1SI
R1SFeX2
+
I2
FeX2I
+
F
C
G
Scheme 4 Possible mechanism for direct sulfenylation of aryl-
amines
Synthesis 2011, No. 7, 1099–1105 © Thieme Stuttgart · New York

PAPER
FeF3-Catalyzed Sulfenylation and Selenation of Arylamines
1101
Table 2 FeF3/I2-Catalyzed Sulfenylation of Aniline (1a) with Disulfides 2a
FeF3 (20 mol%)
R
R
H2N
R
I
2 (10 mol%)
NH2
S
S
+
H2N
S
+
MeCN, 80 °C
R
S
1a
2
A
B
Entry
1
Disulfide 2
Products
Yield (%)b
75 (97:3)
NH2
S
NH2
S
S
2
2b
4A
4B
NH2
S
NH2
S
Cl
S
2
3
4
82 (96:4)
76 (97:3)
60 (90:10)
2
2c
Cl
Cl
5A
5B
NH2
S
NH2
S
F
S
2
2d
F
F
6A
6B
NH2
S
NH2
S
O2N
S
2
2e
O2N
O2N
7A
7B
NH2
S
N
NH2
S
S
5
6
45 (89:11)
27 (75:25)
2
N
N
2f
8A
8B
NH2
Me
S
NH2
S
S
Me
S
Me
Me
9A
2g
9B
a Reaction conditions: 1a (0.4 mmol), 2 (0.4 mmol), FeF3 (20 mol%), and I2 (10 mol%) in MeCN (3 mL) at 80 °C for 36 h.
b Isolated yield. Ratio of para/ortho-products A and B was determined by GC-MS analysis.
The present results show that the reaction could take place The reaction of HI with RSSR (2) may take place to pro-
in the presence of FeF3 or I2 alone, suggesting an electro- vide the active intermediate RSI (C) and an inactive RSH
philic addition process (Table 1, entry 17). Therefore, a intermediate.
possible mechanism as outlined in Scheme 4 is pro-
In summary, we have developed a new, simple FeF3/I2 co-
catalyzed thiolation method for the synthesis of 4-chalco-
gen-substituted arylamines. Compared with other syn-
thetic methods, the FeF3/I2 catalytic system has the
advantages of simplicity, low cost, and regioselectivity
for the thiolation of arylamines. Moreover, we found the
posed.12,15 Intermediate RSI (C), which is generated in
situ from the reaction of RSSR (2) with I2, undergoes the
electrophilic addition to aniline 1 leading to intermediates
D and/or E with the aid of FeF3 catalyst. Deprotonation of
intermediates D and E affords the desired product and HI.
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Table 3 FeF3/I2-Catalyzed Sulfenylation of Anilines (1) with 1,2-Diphenyl Disulfide (2a)a
FeF3
(20 mol%)
I2
Ph
PhS
NHR1
NHR1
SPh
(10 mol%)
NHR1
S
S
+
+
MeCN
80 °C
Ph
R2
R2
R2
2a
1
A
B
Entry
Amine 1
Products
Yield (%)b
NH2
SPh
NH2
1
2
64
1b
1c
1d
10B
11B
12B
SPh
NH2
PhS
NH2
NH2
62 (91:9)
11A
SPh
NH2
NH2
PhS
NH2
3
58 (99:1)
12A
NH2
PhS
NH2
4
5
63
40
1e
13A
MeO
NH2
SPh
MeO
NH2
1f
14B
SPh
NH2
OMe
NH2
PhS
NH2
OMe
6
7
8
76 (98:2)
OMe
1g
15A
15B
Cl
Cl
Cl
NH2
PhS
NH2
NH2
SPh
83 (>99:1)
23 (>99:1)
MeO
MeO
MeO
1h
16A
16B
SPh
NH2
NH2
PhS
NH2
Cl
Cl
Cl
1i
17A
17B
18B
19B
SPh
NHMe
NHMe
NHAc
PhS
NHMe
NHAc
9
90 (95:5)
trace
1j
18A
SPh
NHAc
PhS
10
1k
19A
a Reaction conditions: 1 (0.4 mmol), 2a (0.4 mmol), FeF3 (20 mol%), and I2 (10 mol%) in MeCN (3 mL) at 80 °C for 36 h.
b Isolated yield. Ratio of para/ortho-products A and B was determined by GC-MS analysis.
FeF3/I2 catalytic system to be a versatile coupling system actions of the other electron-rich aromatic compounds
with wide applicability, producing good yields in both the (mesitylene and 1,3,5-trimethoxybenzene) with diphenyl
reaction of aniline with diphenyl selenides and in the re- disulfide.
Synthesis 2011, No. 7, 1099–1105 © Thieme Stuttgart · New York

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FeF3-Catalyzed Sulfenylation and Selenation of Arylamines
1103
NMR spectroscopy was performed on a Bruker 300 or 500 spec-
trometer operating at 300 MHz (1H NMR) and 75 MHz (13C NMR)
or 500 MHz (1H NMR) and 125 MHz (13C NMR). TMS was used
an internal standard and CDCl3 was used as the solvent. Mass spec-
trometric analysis was performed on GC-MS analysis (Shimadzu
GCMS-QP2010 plus).
1H NMR (300 MHz, CDCl3): d = 3.99 (br s, 2 H), 6.75 (d, J = 9.0
Hz, 2 H), 7.07 (d, J = 9.0 Hz, 2 H), 7.32 (d, J = 9.0 Hz, 2 H), 8.02
(d, J = 9.3 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 151.0, 148.3, 144.7, 137.2, 125.1,
123.8, 116.2, 116.1.
LRMS (EI, 70 eV): m/z (%) = 246 (M+, 100), 200 (25), 167 (14),
124 (42), 57 (26).
FeF3/I2-Catalyzed Synthesis of 4-Chalcogen-Substituted Aryl-
amines; Typical Procedure
4-(Pyridin-2-ylthio)aniline (8A)14a
Brown oil.
1H NMR (300 MHz, CDCl3): d = 3.85 (br s, 2 H), 6.70–6.78 (m, 3
H), 6.93–6.95 (m, 1 H), 7.37–7.41 (m, 3 H), 8.38–8.40 (m, 1 H).
13C NMR (75 MHz, CDCl3): d = 163.6, 149.2, 147.9, 137.3, 136.5,
120.0, 119.1, 117.4, 115.9.
LRMS (EI, 70 eV): m/z (%) = 202 (M+, 63), 201 (100), 124 (19), 78
(13).
A mixture of aniline 1 (0.4 mmol), disulfide 2 (0.4 mmol), FeF3 (20
mol%), and I2 (10 mol%) in MeCN (3 mL) was stirred at 80 °C un-
der N2 atmosphere for 36 h until complete consumption of starting
material was indicated by TLC. After the reaction was complete, the
mixture was poured into EtOAc (5 mL) and the EtOAc layer was
washed with brine (5 mL). The aqueous layer was extracted with
EtOAc (3 × 5 mL) and the combined organic layers were dried
(Na2SO4) and evaporated under vacuum. The residue was purified
by flash column chromatography on silica gel (hexane–EtOAc) to
give the desired product.
4-(Methylthio)aniline (9A)20
Brown oil.
4-(Phenylthio)aniline (3A)16
Pale brown solid; mp 92.2–93.1 °C.
1H NMR (300 MHz, CDCl3): d = 3.79 (br s, 2 H), 6.64 (d, J = 8.5
Hz, 2 H), 7.10–7.13 (m, 5 H), 7.30 (d, J = 8.5 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d =147.0, 139.7, 136.1, 128.8, 127.2,
125.2, 120.3, 115.8.
1H NMR (300 MHz, CDCl3): d = 2.41 (s, 3 H), 3.34 (br s, 2 H), 6.63
(d, J = 8.8 Hz, 2 H), 7.19 (d, J = 8.8 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 145.0, 131.0, 125.8, 115.7, 18.7.
LRMS (EI, 70 eV): m/z (%) = 139 (M+, 82), 124 (100), 80 (40), 44
(13).
LRMS (EI, 70 eV): m/z (%) = 201 (M+, 100), 169 (27), 124 (6), 80
(25).
4-Methyl-2-(phenylthio)aniline (10B)21
Yellow oil.
4-(p-Tolylthio)aniline (4A)4a
Brown solid; mp 68.4–70.5 °C.
1H NMR (300 MHz, CDCl3): d = 2.27 (s, 3 H), 3.62 (br s, 2 H), 6.62
(d, J = 8.5 Hz, 2 H), 7.01–7.09 (m, 4 H), 7.23–7.27 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 146.7, 135.6, 135.5, 135.4, 129.7,
128.2, 121.6, 115.8, 21.0.
LRMS (EI, 70 eV): m/z (%) = 215 (M+, 100), 200 (25), 183 (5), 183
(26), 124 (12), 91 (7).
1H NMR (300 MHz, CDCl3): d = 2.23 (s, 3 H), 4.11 (br s, 2 H), 6.69
(d, J = 8.1 Hz, 1 H), 7.02–7.11 (m, 4 H), 7.17–7.27 (m, 3 H).
13C NMR (75 MHz, CDCl3): d = 146.4, 137.5, 136.9, 131.8, 128.9,
128.0, 126.3, 125.2, 115.4, 114.1, 20.1.
LRMS (EI, 70 eV): m/z (%) = 215 (M+, 100), 200 (20), 138 (8), 77
(24).
3-Methyl-4-(phenylthio)aniline (11A)17
Brown oil.
4-(4-Chlorophenylthio)aniline (5A)17
1H NMR (300 MHz, CDCl3): d = 2.28 (s, 3 H), 3.62 (br s, 2 H), 6.51
(m, 1 H), 6.61 (m, 1 H), 7.00–7.08 (m, 3 H), 7.15–7.20 (m, 2 H),
7.32 (d, J = 8.1 Hz, 1 H).
13C NMR (75 MHz, CDCl3): d = 147.6, 143.9, 139.3, 137.9, 128.7,
126.1, 124.6, 118.9, 117.1, 113.4, 20.8.
LRMS (EI, 70 eV): m/z (%) = 215 (M+, 100), 200 (8), 138 (9), 94
(35), 77 (22).
Brown solid; mp 54.7–56.5 °C.
1H NMR (300 MHz, CDCl3): d = 3.82 (br s, 2 H), 6.66 (d, J = 8.5
Hz, 2 H), 7.02 (m, 2 H), 7.15 (m, 2 H), 7.28 (d, J = 9.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 147.3, 138.5, 136.2, 131.0, 128.9,
128.4, 119.8, 115.9.
LRMS (EI, 70 eV): m/z (%) = 235 (M+, 100), 199 (28), 124 (27), 44
(90).
2-Methyl-4-(phenylthio)aniline (12A)22
Brown solid; mp 60.8–61.3 °C.
4-(4-Fluorophenylthio)aniline(6A)18
Brown solid; mp 58.6–60.3 °C.
1H NMR (300 MHz, CDCl3): d = 2.13 (s, 3 H), 3.73 (br s, 2 H), 6.64
(d, J = 8.0 Hz, 1 H), 7.07–7.12 (m, 3 H), 7.17–7.20 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 145.3, 139.9, 137.0, 133.8, 128.7,
127.0, 125.0, 123.2, 120.0, 115.5, 17.2.
LRMS (EI, 70 eV): m/z (%) = 215 (M+, 100), 200 (13), 183 (21),
138 (19), 77 (20).
1H NMR (300 MHz, CDCl3): d = 3.74 (br s, 2 H), 6.63 (d, J = 8.5
Hz, 2 H), 6.88–6.94 (m, 2 H), 7.10–7.15 (m, 2 H), 7.25 (d, J = 8.5
Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 161.1 (d, JC,F = 243.4 Hz), 146.9,
135.4, 134.2, 129.8 (d, JC,F = 7.8 Hz), 121.1, 115.8 (d, JC,F = 21.7
Hz), 115.7.
2,6-Dimethyl-4-(phenylthio)aniline (13A)18
LRMS (EI, 70 eV): m/z (%) = 219 (M+, 100), 187 (25), 124 (23), 80
Brown oil.
(23).
1H NMR (300 MHz, CDCl3): d = 2.12 (s, 6 H), 3.59 (br s, 2 H),
4-(4-Nitrophenylthio)aniline (7A)19
Yellow solid; mp 138.2–140.5 °C.
7.05–7.20 (m, 7 H).
13C NMR (75 MHz, CDCl3): d = 143.7, 140.2, 135.0, 128.8, 127.0,
125.0, 122.7, 119.1, 17.5.
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X.-L. Fang et al.
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LRMS (EI, 70 eV): m/z (%) = 229 (M+, 100), 214 (11), 197 (24),
4-(Methylselanyl)aniline (21A)27
152 (17), 120 (6), 91 (16), 77 (10).
Brown oil.
1H NMR (300 MHz, CDCl3): d = 2.66 (s, 3 H), 3.72 (br s, 2 H), 6.61
(d, J = 9.0 Hz, 2 H), 7.31 (d, J = 9.0 Hz, 2 H).
13C NMR (75 MHz, CDCl3): d = 145.5, 133.9, 118.5, 115.8, 9.0.
LRMS (EI, 70 eV): m/z (%) = 187 (M+, 100), 172 (62).
4-Methoxy-2-(phenylthio)aniline (14B)23
Yellow oil.
1H NMR (300 MHz, CDCl3): d = 3.73 (s, 3 H), 6.73–6.76 (m, 1 H),
6.85 (d, J = 7.5 Hz, 1 H), 7.01–7.03 (m, 1 H), 7.09–7.14 (m, 3 H),
7.20–7.25 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 152.4, 142.7, 136.5, 129.1, 126.7,
125.6, 121.0, 118.2, 116.7, 115.3, 55.9.
LRMS (EI, 70 eV): m/z (%) = 231 (M+, 100), 216 (44), 200 (5), 154
(6), 77 (8).
Mesityl(phenyl)sulfide (25)16
Yellow oil.
1H NMR (500 MHz): d = 7.19 (s, 2 H), 7.1–7.18 (m, 1 H), 6.99–6.94
(m, 2 H), 7.56 (d, J = 7.5 Hz, 2 H), 2.31 (s, 6 H), 2.25 (s, 3 H).
13C NMR (125 MHz): d = 143.7, 139.3, 138.4, 129.3, 128.8, 125.4,
124.4, 21.7, 21.1.
LRMS (EI, 70 eV): m/z (%) = 228 (M+, 100), 91 (28), 119 (14), 150
2-Methoxy-4-(phenylthio)aniline (15A)24
Brown solid; mp 54.9–56.1 °C.
1H NMR (300 MHz, CDCl3): d = 3.72 (s, 3 H), 6.59 (d, J = 8.0 Hz,
(28), 229 (160).
1 H), 6.85–6.92 (m, 2 H), 7.01–7.14 (m, 5 H).
Phenyl(2,4,6-trimethoxyphenyl)sulfide (26)28
White solid; mp 119.6–121.5 °C.
1H NMR (300 MHz, CDCl3): d = 3.76 (s, 6 H), 3.82 (s, 3 H), 6.18
(s, 2 H), 6.97–7.01 (m, 3 H), 7.09–7.14 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 162.9, 162.5, 138.6, 128.4, 125.5,
124.3, 98.4, 91.1, 56.2, 55.4.
LRMS (EI, 70 eV): m/z (%) = 276 (M+, 100).
13C NMR (75 MHz, CDCl3): d = 147.4, 139.8, 137.0, 128.7, 128.3,
126.9, 125.1, 119.7, 116.6, 115.0, 55.5.
LRMS (EI, 70 eV): m/z (%) = 231 (M+, 100), 216 (35), 199 (6), 154
(6), 139(4), 78 (8).
2-Chloro-5-methoxy-4-(phenylthio)aniline (16A)
Brown solid; mp 65.7–66.8 °C.
1H NMR (300 MHz, CDCl3): d = 3.72 (s, 3 H), 4.23 (br s, 2 H), 6.32
(s, 1 H), 7.08–7.12 (m, 3 H), 7.18–7.24 (m, 2 H), 7.32 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 159.3, 145.0, 137.8, 136.4, 128.8,
127.2, 125.4, 110.6, 109.2, 98.9, 55.1.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.
LRMS (EI, 70 eV): m/z (%) = 265 (M+, 93), 230 (100), 215 (15),
186 (25), 115 (17), 77 (10).
Acknowledgment
HRMS (EI): m/z calcd for C13H12ClNOS (M+): 265.0328; found:
265.0331.
The authors thank the National Natural Science Foundation of
China (Nos. 20872112 and 21002070), Program of Science and
Technology of Wenzhou (Nos. Y20090243 and G20090080), and
Zhejiang Provincial Natural Science Foundation of China (Nos.
Y407116 and Y4080169) for financial support.
2-Chloro-4-(phenylthio)aniline (17A)25
Brown oil.
1H NMR (300 MHz, CDCl3): d = 4.19 (br s, 2 H), 6.74 (d, J = 8.3
Hz, 1 H), 7.13–7.25 (m, 6 H), 7.42 (s, 1 H).
13C NMR (75 MHz, CDCl3): d = 143.4, 138.6, 135.1, 134.0, 129.0,
127.9, 125.8, 121.7, 119.4, 116.3.
References
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N-Methyl-4-(phenylthio)aniline (18A)17
Yellow oil.
1H NMR (300 MHz, CDCl3): d = 2.83 (s, 3 H), 3.88 (br s, 1 H), 6.58
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4-(Phenylselanyl)aniline (20A)26
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126.0, 116.3, 116.0.
LRMS (EI, 70 eV): m/z (%) = 249 (M+, 35), 169 (100).
Synthesis 2011, No. 7, 1099–1105 © Thieme Stuttgart · New York

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