Poly[4-diacetoxyiodo] styrene-promoted thiocyanation of aromatic ethers, anilines, and indoles

Article abstract of DOI:10.1080/10426507.2010.496748

Chemical Equation Presented Thiocyanation of aromatic ethers, anilines, and indoles have been achieved using ammonium thiocyanate in the presence of poly[4-diacetoxyiodo] styrene (PDAIS) in CH3CN at room temperature. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/10426507.2010.496748

Phosphorus, Sulfur, and Silicon, 186:304–310, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.496748
POLY[4-DIACETOXYIODO] STYRENE–PROMOTED
THIOCYANATION OF AROMATIC ETHERS, ANILINES,
AND INDOLES
Liqiang Wu,1 Shujun Chao,2 Xiao Wang,1 and Fulin Yan1
1School of Pharmacy, Xinxiang Medical University, Xinxiang, Henan, China
2Department of Chemistry, Xinxiang Medical University, Xinxiang, Henan, China
GRAPHICAL ABSTRACT
SCN
R1O
R3
R1O
R2
R2
R4
SCN
PS
CH3CN, rt
I(OAc)2
R3
+ NH4SCN
N
R4
N
R3
R3
SCN
R6
N
R5
R6
R7
R7
N
R5
Abstract Thiocyanation of aromatic ethers, anilines, and indoles have been achieved using
ammonium thiocyanate in the presence of poly[4-diacetoxyiodo] styrene (PDAIS) in CH3CN
at room temperature.
Keywords Anilines; aromatic ethers; indoles; poly[4-diacetoxyiodo] styrene thiocyanation
INTRODUCTION
The electrophilic thiocyanation of aromatic and hetereoaromatic compounds as a di-
rect method for carbon–sulfur bond formation is a very useful reaction in organic synthesis.1
Aryl and heteroaryl thiocyanates are important intermediates for the synthesis of sulfur-
containing heterocycles.2 The thiocyanate group can also be converted into other sulfur-
bearing groups.3 Therefore, it is important to find new and fast methods for the synthesis
of thiocyanate groups containing aromatic systems. Various methods have been reported
Received 25 April 2010; accepted 24 May 2010.
We are pleased to acknowledge the financial support from Xinxiang Medical University.
Address correspondence to Liqiang Wu, School of Pharmacy, Xinxiang Medical University, Xinxiang,
Henan 453003, China. E-mail: wliq1974@sohu.com
304

THIOCYANATION OF AROMATIC ETHERS
305
for the thiocyanation of aromatic systems using ceric ammonium nitrate,4a NaBO3,4b acidic
K10 clay,4c iodine/MeOH,4d FeCl34e oxone,4f DDQ,4g SelectfluorTM 4h I2O5,4i Mn(OAc)3,4j
,
2-iodoxybenzoate,4k Al2O3/MeSO3H,4l p-TsOH,4m PhI(OAc)2,4n HIO3.4o However, many
of the methods utilizing these reagents suffer from various drawbacks, such as the use of
excess amounts of strong oxiding agents and expensive reagents, unsatisfactory yield, and
high temperatures.
Poly[4-diacetoxyiodo] styrene (PDAIS) is a novel and versatile oxidizing agent, due
to its high efficiency, reusability, and mild reaction conditions. PDAIS has been explored as a
powerful oxidant for various organic transformations under mild conditions.5 In this article,
we report a simple, efficient, and practical approach for the thiocyanation of aromatic ethers,
anilines, and indoles using ammonium thiocyanate in the presence of PDAIS in CH3CN at
room temperature (Scheme 1).
SCN
R1O
R2
R1O
R2
SCN
PS
CH3CN, rt
I(OAc)2
R3
+
R3
NH4SCN
N
R3
R4
N
R3
R4
2
SCN
R6
N
R5
R6
R7
R7
N
R5
3
1
Scheme 1
RESULTS AND DISCUSSION
To choose the optimum conditions, first, the effect of the solvent on the rate of
the reaction was studied for the preparation of 1-methoxy-4-thiocyanatobenzene from the
reaction of anisole (1 mmol), NH4SCN (2.5 mmol), and PDAIS (1.2 mmol) in several
solvents or under solvent-free conditions at room temperature (Table 1). In CH3CN, the
reaction proceeded smoothly with a short reaction time and high yield.
Next, to determine the optimum amount of PDAIS, the reaction was carried out by
varying the amount of the oxidant (Table 2). The maximum yield was obtained with 1.2
equivalents of PDAIS. Further increases in amount of the oxidant in the standard reaction
did not have any significant effect on the product yield.
Using these optimized reaction conditions, the scope and efficiency of these proce-
dures were explored for the thiocyanation of a variety of aromatic ethers, anilines, and
indoles. The results are summarized in Table 3. As shown in Table 3, aromatic ethers, ani-
lines, and indoles containing electron-donating as well as electron-withdrawing groups were
smoothly converted. The reaction is highly regioselective, forming 4-thiocyano aromatic
ethers, anilines, and 3-thiocyano indoles as the products. The structures of the thiocyanates

306
L. WU ET AL.
Table 1 Solvent optimization for the synthesis of 1-methoxy-4-thiocyanatobenzene
Entry
Solvent
Time (h)
Yield (%)a
1
2
3
4
5
6
MeOH
H2O
CH2Cl2
DMF
CH3CN
neat
1
3
1
1.5
1
65
0
80
72
90
23
1
aIsolated yield.
were established from their IR, 1H NMR, 13C NMR, and elemental analyses. This method-
ology offers significant improvements with regard to the scope of this transformation and
simplicity in operation.
After the reaction, PDAIS was converted to polyiodostyrene, which was recovered by
simple filtration. The regeneration of PDAIS was achieved by reaction of polyiodostyrene
in acetic anhydride with dropwise addition of 32 mL of cold hydrogen peroxide (30%
solution) (Scheme 2). The reaction mixture was stirred at room temperature for 16 h. The
above reaction mixture was kept overnight at room temperature. The PDAIS product was
precipitated with diethyl ether and then dried for use. The recovered PDAIS can be reused
at least four additional times in subsequent reactions without significant loss in product
yield (Table 4).
PS
I
H2O2, Ac2O
I(OAc)2
PS
Scheme 2
The mechanism of the reaction may involve the initial nucleophilic attack of thio-
cyanate anion on the fairly electrophilic PDAIS, through a phenomenon of ligand exchange
Table 2 PDAIS optimization for the synthesis of 1-methoxy-4-thiocyanatobenzenea
Entry
PDAIS/equivalent
Time (h)
Yield (%)b
1
2
3
4
5
6
7
8
0
4
2
1.5
1
1
1
1
1
0
42
72
82
90
90
89
88
0.5
1.0
1.1
1.2
1.3
1.4
1.5
aReaction conditions: anisole (1 mmol); NH4SCN (2.5 mmol); rt; CH3CN.
bIsolated yield.

THIOCYANATION OF AROMATIC ETHERS
307
Table 3 Thiocyanation of aromatic ethers, anilines, and indoles promoted by PDAISa
Entry
Substrate
Productb
Time (h) Yield (%)c
Mp (lit.) (◦C)
36–39 (41)4n
a
1
1
1
1
90
91
86
88
b
c
Oil (Oil)4n
Oil (Oil)4n
d
102–104 (104–106)4o
e
f
1.5
1.5
82
85
51–53 (51–52)4g
71–73 (71–72) 4g
g
1.5
1
88
82
61–63 (60–61)4g
h
100–101 (99–100)4g
i
1
1
80
89
110–112 (105–106)4g
80–81 (83–84)4g
j
k
l
1
1
78
76
99–101 (99–101)4g
125–126 (127–129)4g
(Continued on next page)

308
L. WU ET AL.
Table 3 Thiocyanation of aromatic ethers, anilines, and indoles promoted by PDAISa (Continued)
Entry
Substrate
Productb
Time (h)
Yield (%)c
82
Mp (lit.) (◦C)
m
1.5
113–115 (113–115)4f
n
1.5
84
110–112
aReaction conditions: aromatic ethers, anilines or indoles (1 mmol); NH4SCN (2 .5mmol); PDAIS (1.2 mmol);
rt; CH3CN.
bAll products except 2n were identified by comparing their physical and spectral data with those of the authentic
samples (see references 4f, 4g, 4n, 4o).
cIsolated yield.
to form the intermediate. The overwhelming tendency of the intermediate to expel iodoben-
zene is expected to generate the rather unstable thiocyanogen required for the aromatic
electrophilic thiocyanation reaction (Scheme 3).
+
PS
(SCN)2
PS
I
PS
I(OAc)2
+
I(SCN)2
2NH4SCN
SCN
(SCN)2
MeO
MeO
Scheme 3
To emphasize the effect of oxidant, the model reaction between anisole with NH4SCN
was described, and different hypervalent iodine oxidants were subjected to the reaction.
All the reactions were run in the same conditions, and similar amounts of oxidant (1.2
equivalent) were used. As can be seen in Table 5, satisfactory results were obtained only
with PDAIS (entry 7).
Table 4 The effect of reusability of PDAISa
Run
Cycle
Yield (%)b
1
2
3
4
5
0
1
2
3
4
90
90
88
88
86
aReaction conditions: anisole (1 mmol); NH4SCN (2.5 mmol); PDAIS (1.2 mmol); rt; CH3CN.
bIsolated yield.

THIOCYANATION OF AROMATIC ETHERS
309
Table 5 Effect of hypervalent iodine oxidant on the reaction of anisole with NH4SCNa
Entry
Hypervalent iodine oxidant
Time (min)
Solvent
Yield (%)b
1
2
3
4
5
6
7
Dess–Martin periodinane
o-Iodoxylbenzoic acid
HIO3
I2O5
HIO4
PhI(OAc)2
PDAIS
60
30
30
60
60
30
60
CH3CN
CH3CN
CHCl3
MeOH
CHCl3
52
70
82
62
58
81
90
CH3CN
CH3CN
aReaction conditions: anisole (1 mmol); NH4SCN (2.5 mmol); hypervalent iodine oxidant (1.2 mmol); rt.
bIsolated yield.
CONCLUSION
In summary, PDAIS can effectively promote the reaction of ammonium thiocyanate
with aromatic ethers, anilines, and indoles to afford thiocyanated products. The reactions
are conducted under mild conditions and afford regioselective thiocyanated products in
good to excellent yields.
EXPERIMENTAL
NMR spectra were determined on Bruker AV-400 spectrometer at room temperature
using TMS as internal standard, and coupling constants (J) were measured in Hz. Elemental
analyses were performed by a Vario-III elemental analyzer. Melting points were determined
on a XT-4 binocular microscope and were uncorrected. PDAIS was synthesized according
to the reported procedure.5b Commercially available reagents were used throughout without
further purification unless otherwise stated.
General Procedure for the Thiocyanation of Indoles and Anilines
To a solution of aromatic ethers, anilines, or indoles (1.0 mmol) and NH4SCN (2.5
mmol) in CH3CN (20 mL), PDAIS (1.2 mmol) was added at room temperature. The reaction
mixture was stirred at room temperature for the appropriate time according to Table 3. After
complete conversion as indicated by TLC, the reaction mixture was quenched with water
(20 mL) and extracted with CHCl3 (2 × 20 mL). The solvent was evaporated, and the crude
product was purified by silica gel column chromatography using ethyl acetate/hexane (1:9)
as an eluent to afford the pure product. The characterization data for the new product are
given below.
5-Fluoro-3-thiocyanato-1H-indole (3n)
Solid, IR (KBr): v 3428, 2141, 1638, 1452 cm−1.1H NMR (400 MHz, CDCl3): δ 8.72
(1H, brs), 7.29–7.00 (4H, m), 2.88 (3H, s); 13C NMR (100 MHz, CDCl3): δ 137.2, 133.2,
131.8, 126.2, 125.0, 122.9, 115.6, 109.9, 90.5, 20.4. Anal. calcd for C9H5FN2S: C 56.24,
H 2.62, N 14.57, S 16.68; found: C 56.18, H 2.71, N 14.50, S 16.50.

310
L. WU ET AL.
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