I2O5 as a mild, inexpensive, and environmentally benign oxidant for the α-thiocyanation of ketones

Article abstract of DOI:10.1080/17415993.2010.548099

-Thiocyanation of various ketones has been achieved using ammonium thiocyanate as a thiocyanation reagent and I₂O₅ as an oxidant in methanol solution at room temperature. Figure Presented.

Full text of DOI:10.1080/17415993.2010.548099

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I2O5 as a mild, inexpensive, and
environmentally benign oxidant for the
α -thiocyanation of ketones
Liqiang Wu a , Xiaojuan Yang b & Fulin Yan a
a School of Pharmacy, Xinxiang Medical University, Xinxiang,
Henan, 453003, People's Republic of China
b College of Chemistry and Chemical Engineering, Xinxiang
University, Xinxiang, Henan, 453003, People's Republic of China
Version of record first published: 24 Jan 2011.
To cite this article: Liqiang Wu , Xiaojuan Yang & Fulin Yan (2011): I2O5 as a mild, inexpensive, and
environmentally benign oxidant for the α -thiocyanation of ketones, Journal of Sulfur Chemistry,
32:2, 105-110
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Journal of Sulfur Chemistry
Vol. 32, No. 2, April 2011, 105–110
I2O5 as a mild, inexpensive, and environmentally benign oxidant
for the α-thiocyanation of ketones
Liqiang Wua*, Xiaojuan Yangb and Fulin Yana
aSchool of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, People’s Republic of China;
bCollege of Chemistry and Chemical Engineering, Xinxiang University, Xinxiang, Henan 453003, People’s
Republic of China
(Received 5 October 2010; final version received 12 December 2010)
α-Thiocyanation of various ketones has been achieved using ammonium thiocyanate as a thiocyanation
reagent and I2O5 as an oxidant in methanol solution at room temperature.
O
O
I2O5
R2
+
R2
NH4SCN
R1
R1
MeOH, rt
SCN
Keywords: thiocyanation; ketones; ammonium thiocyanate; I2O5; synthesis
1. Introduction
Thiocyanate is a versatile synthon (1), which can be readily transferred to other functional groups
such as sulfide (2), aryl nitrile (3), thiocarbamate (4), and thionitrile (5). The development of new
synthetic methods for introducing thiocyanate functionality is always demanded. α-Thiocyanato
carbonyl compounds are valuable precursors for the synthesis of heterocyclic ring systems such
as 2-amino-1,3-thiazines, thiazoles, and their derivatives (1), some of which are associated with
herbicidal and other biological activities (6). Thiocyanato group plays an important role in certain
anticancer natural products formed by deglycosylation of glucosinolates derived from cruciferous
vegetables (7).
Several methods have been developed for the thiocyanation of ketones using bro-
modimethylsulfonium bromide/ammonium thiocyanate (8), oxone/ammonium thiocyanate
(9), heteropolyacid/ammonium thiocyanate (10), (dichloroiodo)benzene/lead (II) thiocyanate
(11), potassium peroxydisulfate/copper(II) complex (12), and I2/ammonium thiocyanate (13).
However, many of these methodologies are associated with one or more disadvantages such as
(i) harsh reaction conditions, e.g. treatment with 1.2 equiv. (dichloroiodo)benzene/lead (II) thio-
cyanate at 0 ◦C in CH2Cl2 for 2–4 h (11) and heating at 70 ◦C in aq. CH3CN in the presence of 2.0
equiv. potassium peroxydisulfate/copper (II) complex for 1–5 h (12), (ii) prolonged reaction time
*Corresponding author. Email: wliq870@163.com
ISSN 1741-5993 print/ISSN 1741-6000 online
© 2011 Taylor & Francis
DOI: 10.1080/17415993.2010.548099
http://www.informaworld.com

106 L. Wu et al.
(9, 11–13), and (iii) requirement of hazardous and carcinogenic organic solvents such as CH3CN
(12) and CH2Cl2 (8, 10, 11). Thus, the development of environmentally benign, high yielding,
and clean approaches for the α-thiocyanation of ketones is in demand.
Recently, the use of hypervalent iodine reagents as oxidants in organic synthesis has attracted
increasing interest due to their mild, selective, and environmentally benign oxidizing properties
(14). I2O5 is one of the most versatile oxidizing agents due its safe, benign, economic, commer-
cially available, and environmentally friendly nature (15). It has been extensively used in industry
and organic synthesis (15, 16). In this article, we report a direct and metal-free approach to the
α-thiocyanation of ketones using I2O5 in methanol solution (Scheme 1).
O
O
I2O5
R2
+
R2
NH4SCN
R1
R1
MeOH, rt
SCN
1
2
Scheme 1. α-thiocyanation of ketones using I2O5.
2. Results and discussion
First, we attempted α-thiocyanation of acetophenone (1a) with ammonium thiocyanate using a
stoichiometric amount of I2O5. The reaction went to completion within 20 min at room temper-
ature, and the desired product, 1-phenyl-2-thiocyanatoethanone (2a), was obtained in 88% yield
(Table 1, Entry a).
Table 1. α-Thiocyanation of ketones promoted by I2O5.a
Entry
Ketones
Product
Time (min)
20
Yield (%)b
88
Reference
a
(8)
O
O
SCN
b
c
25
30
20
15
85
83
89
92
(8)
(8)
(8)
O
O
SCN
Cl
Cl
O
O
SCN
O2N
O2N
d
e
O
O
SCN
H3CO
H3CO
O
O
(8)
SCN
(Continued)

Journal of Sulfur Chemistry 107
Table 1. Continued
Entry
Ketones
Product
Time (min)
30
Yield (%)b
81
Reference
f
(10)
Cl
O
Cl
O
SCN
SCN
g
35
79
(10)
O
O
Br
Br
h
i
35
30
80
78
The work
The work
Br
O
O
Br
O
SCN
Br
Br
O
SCN
j
40
45
85
88
(8)
(8)
O
O
SCN
k
O
O
SCN
l
50
50
86
84
(10)
(10)
O
O
SCN
m
O
O
SCN
n
o
45
40
79
82
(9)
(9)
O
O
SCN
O
O
SCN
Notes: aReaction conditions: ketones (1.0 mmol); NH4SCN (2.0 mmol); I2O5 (1.0 mmol); rt; MeOH. bIsolated yield.

108 L. Wu et al.
This result provided an incentive to study further reactions with various acetophenone
derivatives (Entries b–i, Table 1) such as 4-chloroacetophenone, 4-nitroacetophenone, 4-
methoxylacetophenone, 4-methylacetophenone, 2-chloroacetophenone, 3-bromoacetophenone,
2,4-dibromoacetophenone, and 3,3-dimethyl-1-phenylbutan-1-one. The presence of electron-
donating groups on acetophenone increases the yields of products (Entries d and e, Table 1).
Similarly, various cyclic ketones such as cyclohexanone, cyclopentanone, 1-tetralone, and
indanone (Entries j–m, Table 1) also reacted readily with ammonium thiocyanate to give the corre-
sponding α-thiocyanated products in good yields. When compared with acetophenone derivatives,
aliphatic ketones reacted rapidly to give α-thiocyanated products (Entries n–o, Table 1). The main
advantage of this method is that a variety of ketones having α-hydrogens readily underwent thio-
cyanation at room temperature. All the products were characterized by IR, 1H NMR, and element
analysis and by comparison with known samples. IR spectra showed the characteristic peaks−o1f
−1
−
−
SCN group between 2120 and 2160 cm and the C S stretching between 650 and 760 cm
.
The scope of this methodology is demonstrated with respect to various ketones, and the results
are presented in Table 1.
The solvent effect on product yields was investigated using 1a as a substrate. Both the yields
and reaction times listed in Table 2 suggest that methanol appears to be very favorable for
thiocyanations. Therefore, methanol is the solvent of choice for the thiocyanation of ketones.
Mechanistically, the reaction may proceed via the electrophilic substitution of acetophenone
by thiocyanogen (+SCN) formed in situ from I2O5 and ammonium thiocyanate (Scheme 2).
To emphasize the effect of the oxidant, a model reaction between acetophenone and ammonium
thiocyanate is described, and different hypervalent iodine oxidants were subjected to the reaction.
All the reactions were run under the same conditions and similar amounts of oxidant (1 equiv.)
were used. As can be seen in Table 3, satisfactory results were obtained only with I2O5 (Entry 4).
To illustrate the efficiency of the proposed method, Table 4 compares some of our results with
some of those reported for relevant reagents in the literature, which demonstrates its significant
superiority. Compared with some of the reported methods in Table 4, the present method has a
short reaction time, good yield, and solvent-free conditions.
Table 2. Solvent effect on the reaction of acetophenone and ammonium thiocyanate.
Entry
Solvent
Time (min)
Yield (%)a
1
2
3
4
5
6
7
CH3CN
CH2Cl2
CHCl3
CCl4
EtOH
MeOH
THF
60
45
45
60
25
20
35
46
53
59
40
75
86
71
Note: aIsolated yield.
+SCN
+
I2O5 NH4SCN
O
O
SCN
+SCN
+
Scheme 2. The plausible mechanism of the reaction.

Journal of Sulfur Chemistry 109
Table 3. Effect of hypervalent iodine oxidant on the reaction of acetophenone and ammonium thiocyanate.a
Entry
Hypervalent iodine oxidant
Time (min)
Solvent
Yield (%)b
1
2
3
4
5
6
Dess–Martin periodinane
o-Iodoxylbenzoic acid
35
25
20
20
20
30
CH3CN
CH3CN
CHCl3
MeOH
CHCl3
CH3CN
52
70
72
86
53
68
HIO3
I2O5
HIO4
PhI(OAc)2
Notes: aReaction conditions: acetophenone (1 mmol); NH4SCN (2 mmol); hypervalent iodine oxidant (1 mmol); rt. bIsolated yield.
Table 4. α-Thiocyanation of acetophenone in comparison with other literatures.
Entry
Catalyst and conditions
Solvent
Time (h)
Yield (%)
Reference
1
2
3
4
Oxone (1.2 equiv.)/NH4SCN thiocyanate(2.0 equiv.); r.t.
I2 (1. equiv.)/NH4SCN (2.0 equiv.); reflux
Bromide (1.1 equiv.)/NH4SCN (2.0 equiv.); r.t.
I2O5 (1.0 equiv.)/NH4SCN (2.0 equiv.); r.t.
MeOH
MeOH
CH2Cl2
MeOH
6
6
0.33
0.33
86
85
95
86
(9)
(13)
(8)
The work
3. Conclusion
In conclusion, I2O5 has proved to be an effective reagent for the α-thiocyanation of various
ketones under extremely mild and neutral conditions. In addition to its simplicity and efficiency,
this method affords the desired thiocyanates in excellent yields in short reaction times.
4. Experimental
4.1. General
IR spectra were determined on an FTS-40 infrared spectrometer; NMR spectra were recorded
on a Bruker AV-400 spectrometer at room temperature using TMS as an internal standard, and
coupling constants (J) were measured in hertz. Elemental analyses were performed using aVario-
III elemental analyzer; melting points were determined on a XT-4 binocular microscope and were
uncorrected. Commercially available reagents were used throughout without further purification
unless otherwise stated.
4.2. General procedure for the preparation of 2
To a stirred solution of ammonium thiocyanate (2 mmol) and ketones (1 mmol) in MeOH (10 mL),
I2O5 (1 mmol) was added. The resulting mixture was allowed to stir at room temperature for an
appropriate time (Table 1). After completion of the reaction (TLC), the reaction mixture was
quenched with water. The reaction mixture was successively extracted with ethyl acetate, washed
with Na2S2O3, and dried over anhydrous Na2SO4. The solvent was then removed under reduced
pressure. The resulting product was purified by column chromatography on silica gel (200–300
mesh, ethyl acetate:hexane = 1 : 20) to afford pure 2. All products were identified by 1H NMR,
IR, and elemental analyses.

110 L. Wu et al.
4.3. Spectral data for new compounds
4.3.1. 1-(2,4-Dibromophenyl)-2-thiocyanatoethanone (2h)
IR (KBr): v 3152, 2985, 2152 ( SCN), 1674, 1594, 1200, 996 813, 709 (C S) cm−1; 1H NMR
−
−
(CDCl3, 400 MHz) δ: 8.06–7.55 (m, 3H), 4.82 (s, 2H); Anal. Calcd for C9H5Br2NOS C 32.27,
:
H 1.50, N 4.18, S 9.57; found: C 32.20, H 1.56, N 4.10, S 9.49.
4.3.2. 3,3-Dimethyl-1-phenyl-2-thiocyanatobutan-1-one (2i)
1
IR (KBr): v 3058, 2947, 2149 ( SCN), 1676, 1590, 982 745 (C S) cm−1; H NMR (CDCl3,
−
−
400 MHz) δ: 7.98 (d, 2H, J = 7.6 Hz), 7.68 (t, 1H, J = 7.6 Hz), 7.49 (t, 2H, J = 7.6 Hz), 4.92
(s, 1H), 1.01 (s, 9H); Anal. Calcd for C13H15NOS C 66.92, H 6.48, N 6.00, S 13.74; found: C C
:
67.01, H 6.39, N 6.10, S 13.69.
Acknowledgement
We are pleased to acknowledge the financial support from Xinxiang Medical University.
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