Selectfluor: A novel and efficient reagent for the rapid α-thiocyanation of ketones

Article abstract of DOI:10.1007/s12039-012-0270-0

The direct α-thiocyanation of ketones with ammonium thiocyanate has been achieved using Selectfluor under mild and neutral conditions to produce α-ketothiocyanates, in excellent yields and with high selectivity.

Full text of DOI:10.1007/s12039-012-0270-0

c
J. Chem. Sci. Vol. 124, No. 4, July 2012, pp. 901–905. ꢀ Indian Academy of Sciences.
SelectfluorTM: A novel and efficient reagent for the rapid
α-thiocyanation of ketones
DEZHEN WUa, XIAOJUAN YANGb and LIQIANG WUc,∗
aDepartment of Pharmacy, Xinxiang Central Hospital, Xinxiang, Henan 453000, China
bCollege of Chemistry and Chemical Engineering, Xinxiang University, Xinxiang, Henan 453003, China
cSchool of Pharmacy, Xinxiang Medical University, Xinxiang, Henan 453003, China
e-mail: wliq870@163.com
MS received 1 August 2011; revised 16 October 2011; accepted 2 December 2011
Abstract. The direct α-thiocyanation of ketones with ammonium thiocyanate has been achieved using
SelectfluorTM under mild and neutral conditions to produce α-ketothiocyanates, in excellent yields and with
high selectivity.
Keywords. Thiocyanation; ketones; ammonium thiocyanate; SelectfluorTM; synthesis
1. Introduction
widely used for site-selective fluorination of a variety
of carbonyl compounds. Besides its fluorinating abil-
ity, it is also recognized as a convenient mediator of
several ‘fluorine free’ functionalization of organic com-
pounds.13 These kinds of reactions are based on the fact
that F-TEDA-BF4 has considerable oxidative power. In
this article, we report a simple, convenient, and effi-
cient protocol for the α-thiocyanation of ketones using
SelectfluorTM in acetonitrile (scheme 1).
Molecules with thiocyanate functional group can be
readily transformed into the other sulphur-bearing func-
tionalities,1 providing compounds with pharmaceutical
properties.2 In particular, α-ketothiocyanates are versa-
tile intermediates in the synthesis of sulphur-containing
heterocycles.3 Some of these compounds exhibit herbi-
cidal and other important biological activities.4 There-
fore, it is important to find new methods for the direct
α-thiocyanation of ketones. Several methods have been
developed for the direct α-thiocyanation of ketones using
bromodimethylsulphonium bromide/ammonium thio-
cyanate,5 oxone/ammonium thiocyanate,6 heteropoly
acid/ammonium thiocyanate,7 (dichloroiodo)- benzene/
lead(II) thiocyanate,8 potassium peroxydisulphate/
copper(II) complex,9 I2/ammonium thiocyanate,10 FeCl3/
ammonium thiocyanate,11 and NBS/ammonium thio-
cyanate.12 However, some of these methods suffer
from disadvantages, such as low yields, the use of
strongly acidic or oxidizing conditions, the use of spe-
cial conditions (long reaction time and (or) high tem-
perature), and also the use of toxic reagents. In this
research, we have developed a new route for the direct
α-thiocyanation of ketones.
Cl
N
N
F
2BF4
Figure 1. Structure of SelectfluorTM
.
SelectfluorTM (1-chloromethyl-4-fluoro-1,4-diazonia-
bicyclo[2,2,2]octanebis(tetrafluoro-borate)) (figure 1)
is a commercially available, stable, nonvolatile, non-
hygroscopic and easy to handle solid and is more
O
SelectfluorTM
CH3CN, rt
O
R2
+
R2
NH4SCN
R1
R1
SCN
3 (a−n)
2
1 (a−n)
∗For correspondence
Scheme 1. α-Thiocyanation of ketones.
901

902
Dezhen Wu et al.
a
Table 1. α-Thiocyanation of ketones promoted by SelectfluorTM
.
Entry
Ketones (1)b
Product (3)b
Time/ min Yield/ %b m.p. (lit.)/ ◦C
O
O
SCN
a
40
50
93
89
68–70
(67–69)11
O
O
SCN
SCN
Cl
Cl
b
c
133–135
(132–134)5
O
O
O2N
O2N
50
90
118–120
(119–120)5
O
O
SCN
H3CO
H3CO
d
e
40
40
91
86
120–122
(121–125)5
O
O
SCN
104–107
(103–106)5
O
O
SCN
Cl
Cl
Cl
Cl
f
50
60
88
89
65–66
(68–70)11
O
O
SCN
SCN
Cl
Cl
g
191–193
(190–192)11
OMe O
OMe O
h
i
60
25
86
94
86–88
(85–87)11
O
O
SCN
Oil (oil)11

SelectfluorTM: A novel and efficient reagent for the rapid α-thiocyanation of ketones
Table 1. (continued)
903
Entry
Ketones (1)b
Product (3)b
Time/ min
Yield/ %b
m.p. (lit.)/ ◦C
O
O
SCN
j
25
40
91
92
Oil (oil)11
O
O
SCN
k
90–92
(92–93)14
O
O
SCN
l
40
75
60
88
84
87
Oil (oil)11
Oil (oil)11
Oil
O
O
O
SCN
m
n
O
SCN
aReaction conditions: ketones (1.0 mmol); NH4SCN (2.0 mmol); SelectfluorTM (1 mmol); rt;
CH3CN.
bIsolated yield
2. Experimental
silica gel (200–300 mesh, ethyl acetate:hexane = 1:20)
to afford pure 3.
2.1 Materials, methods and instruments
NMR spectra were recorded on a Bruker AV-400 spec-
trometer at room temperature using TMS as internal
standard, coupling constants (J) were measured in Hz.
Elemental analysis were performed by a Vario-III ele-
mental 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.
2.3 Spectroscopic data
2.3a 1-phenyl-2-thiocyanatoethanone (3a): Solid,
mp 68–70◦C; IR (KBr): v 2946, 2150 (-SCN),
Cl
N
Cl
N
F
2BF4
N
N
F-SCN
+
NH4
+
+
2.2 General procedure for α-thiocyanation of ketones
2BF4
NH4SCN
To a solution of ammonium thiocyanate (2 mmol) and
ketones (1 mmol) in acetonitrile (10 mL), SelectfluorTM
(1 mmol) was added and the resulting mixture was
stirred at room temperature for an appropriate time
period. After complete conversion as indicated by TLC,
the reaction mixture was quenched with water. The
reaction mixture was successively extracted with ethyl
acetate, and dried over anhydrous Na2SO4. The solvent
was then removed under reduced pressure. The result-
ing product was purified by column chromatography on
O
O
R2
R2
SCN
R1
R1
SCN
3
Scheme 2. A plausible mechanism for this reaction.

904
Dezhen Wu et al.
Table 2. SelectfluorTM-promoted α-thiocyanation of acetophenone in comparison with other
literatures.
Entry
Catalyst and conditions
Solvent
Time/ min
Yield/ %
Ref.
11
6
1
2
3
4
5
FeCl3 (100 mol%); rt
Oxone (100 mol%); rt
CH2Cl2
MeOH
ClCH2CH2Cl
CH3CN
30
360
20
240
40
75
86
86
85
93
7
Heteropoly acid (25 mol%); rt
NBS (100 mol%); rt
12
SelectfluorTM (100 mol%); rt
CH3CN
The work
1
1672 cm−1; H NMR (CDCl3, 400 MHz) δ: 8.02–7.80
A plausible mechanism for this reaction is proposed
(m, 2H), 7.66–7.25 (m, 3H), 4.78 (s, 2H); 13C NMR in scheme 2, the reaction may proceed via the elec-
(CDCl3, 100 MHz) δ: 191.2, 135.0, 133.6, 128.8, 128.0, trophilic substitution of ketones by in situ generated
112.1, 43.1; Anal. calcd for C9H7NOS: C 60.99, H thiocyanogen (+SCN) from Selectfluor and ammonium
3.98, N 7.90, S 18.09; found: C 70.06, H 3.92, N 7.95, thiocyanate (scheme 2).
S 18.00.
To illustrate the efficiency of the proposed method,
table 2 compares some of our results with some of
those reported for relevant reagents in the literature,
which demonstrates its significant superiority. Com-
pared with some of the reported methods in table 2, the
present method has a short reaction time, good yield,
and solvent-free conditions.
2.3b 2-Thiocyanatocyclohexanone (3j): Oil; IR
(KBr): v 2925, 2154 (-SCN), 1702; H NMR (CDCl3,
1
400 MHz) δ: 4.35–4.20 (m, 1H), 2.85–2.38 (m, 3H),
2.20–1.73 (m, 5 H); 13C NMR (CDCl3, 100 MHz) δ:
204.2, 111.8, 60.2, 39.8, 34.6, 24.9, 23.2; Anal. calcd
for C7H9NOS: C 54.17, H 5.84, N 9.02, S 20.66; found:
C 54.11, H 5.92, N 9.12, S 20.60.
4. Conclusion
In summary, SelectfluorTM can effectively promote the
reaction of ammonium thiocyanate with ketones to
afford α-ketothiocyanates. The reactions are conducted
under mild conditions and afford regioselective thio-
cyanated products in good to excellent yields.
2.3c 1-Cyclopropyl-2-thiocyanatoethanone
(3n):
1
Oil; IR (KBr): v 2927, 2152 (-SCN), 1700; H NMR
(CDCl3, 400 MHz) δ: 4.20 (s, 2H), 2.15–2.00 (m,
1H), 1.35–0.98 (m, 4H); 13C NMR (CDCl3, 100 MHz)
δ: 204.3, 111.3, 44.7, 120.5, 12.8; Anal. calcd for
C6H7NOS: C 51.04, H 5.00, N 9.92, S 22.71; found: C
51.12, H 4.94, N 10.01, S 22.65.
Acknowledgement
We acknowledge the financial support from Xinxiang
Central Hospital and Xinxiang Medical University.
3. Results and discussion
References
When a mixture of ammonium thiocyanate (2 mmol),
ketone (1mmol), and a stoichiometric amount of
SelectfluorTM was stirred at room temperature in
CH3CN corresponding α-ketothiocyanates (3a–n) were
obtained in excellent yield (table 1). The reactions were
completed smoothly within 25 to 75 min, and the prod-
ucts were isolated by a simple workup procedure. Vari-
ous ketones such as acetophenones, cyclic ketones, and
aliphatic ketones all gave regioselective products in
good to excellent yields. No fluoride products were
observed under the reaction conditions. All the prod-
ucts were characterized by 1H NMR, 13C NMR, IR, ele-
ment analysis, and by comparison with known samples,
IR spectrum showed the characteristic peak of -SCN at
2122–2168 cm−1.
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