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

Article abstract of DOI:10.1080/00397910802029349

An efficient and direct approach for the α-thiocyanation of ketones with α-hydrogens has been developed using ammonium thiocyanate as a thiocyanating agent and oxone as an oxidant in methanol. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802029349

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Oxone as a Mild, Inexpensive,
and Environmentally
Benign Oxidant for the α-
Thiocyanation of Ketones
M. Anil Kumar a , K. R. Kishore Kumar Reddy a , M.
Veeranarayana Reddy a , C. Devendranath Reddy a &
C. Suresh Reddy a
a Department of Chemistry, Sri Venkateswara
University, Tirupati, India
Published online: 18 Aug 2008.
To cite this article: M. Anil Kumar , K. R. Kishore Kumar Reddy , M. Veeranarayana
Reddy , C. Devendranath Reddy & C. Suresh Reddy (2008): Oxone as a Mild,
Inexpensive, and Environmentally Benign Oxidant for the α-Thiocyanation of Ketones,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 38:13, 2089-2095
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Synthetic Communications1, 38: 2089–2095, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802029349
Oxone as a Mild, Inexpensive, and
Environmentally Benign Oxidant for
the a-Thiocyanation of Ketones
M. Anil Kumar, K. R. Kishore Kumar Reddy, M. Veeranarayana
Reddy, C. Devendranath Reddy, and C. Suresh Reddy
Department of Chemistry, Sri Venkateswara University, Tirupati, India
Abstract: An efficient and direct approach for the a-thiocyanation of ketones
with a-hydrogens has been developed using ammonium thiocyanate as a thio-
cyanating agent and oxone as an oxidant in methanol.
Keywords: Ammonium
Thiocyanation
thiocyanate;
Carbonyl
compounds;
Oxone;
INTRODUCTION
a-Thiocyanation of ketones is a one of the most important methods for
the formation of carbon–sulfur bonds in organic synthesis.[1,2] Thiocya-
nates are found in many biologically important natural products such
as anticancer agents formed by deglycosylation of glucosinolates derived
from cruciferous vegetables.[3] These thiocyanates are versatile intermedi-
ates in the synthesis of various sulfur- bearing heterocyclic compounds
and many of these heterocycles possess herbicidal and other important
biological activities.[4] In view of the versatility of the thiocyanato group
in heterocycle formation, it would be significant to probe the thiocyana-
tion of various ketones. The traditional methods for generating orga-
nic thiocyanates involve multistep synthetic sequences and drastic
reaction conditions because of the poor nucleophilicity of the
thiocyanate anion.[5–8] Recently, there have been some reports on the
Received November 4; 2007.
Address correspondence to C. Suresh Reddy, Department of Chemistry, Sri
Venkateswara University, Tirupati, 517502, India. E-mail: csureshsvu@yahoo.
com.
2089

2090
M. A. Kumar et al.
direct a-thiocyanation of ketones using dichloroiodobenzene=lead(II)
thiocyanates, potassium peroxydisulphate=copper(II) complex, and iodi-
ne=methanol.[9–11] However, some of these reported methodologies for
thiocyanation require large amounts of strong oxidizing agents, toxic
metal thiocyanates, long reaction times, and high temperature; result in
low yields for some compounds; and also involve the formation of a com-
plex mixture of products. Hence, there is a need to develop an alternative
method for a-thiocyanation of ketones. Oxone is a cheap, nontoxic, and
readily accessible oxidizing reagent. It is a versatile oxidizing agent for
a wide range of functional group transformations such as oxidation
of alcohols, alkenes, sulfides, and tert-amines.[12–15] In addition to this,
it is a stable, nonhygroscopic reagent and is easy to handle, which makes
it an environmentally friendly oxidant. The reactions with oxone gener-
ally occur at room temperature. However, there have been no reports
on the use of oxone for the thiocyanation of ketones.
RESULTS AND DISCUSSION
We herein report a simple, efficient, and selective approach for the direct
a-thiocyanation of ketones using oxone as a safe and environmentally
friendly oxidant. Accordingly, treatment of acetophenone (1a) with 2
eq. of ammonium thiocyanate in the presence of 1.2 eq. of oxone in meth-
anol at room temperature gave the a-thiocyanated product (2a) in 86%
yield (Scheme 1).
This method was successfully applied to a number of other acetophe-
none derivatives (entries b–e, Table 1) such as 4-hydroxyacetophenone,
4-methylacetophenone, 3-chloroacetophenone, and butyrophenone. The
presence of electron-donating groups on acetophenone increases the
yields of products (entries b and d, Table 1). Similarly, various cyclic
ketones such as cyclohexanone, cyclopentanone, 1-tetralone, and sub-
stituted indanones (entries f–j, Table 1) also reacted readily with
ammonium thiocyanate to give the corresponding a-thiocyanated pro-
ducts in good yields. When compared to acetophenone derivatives, ali-
phatic ketones reacted rapidly to give a-thiocyanated products (entries
Scheme 1.

a-Thiocyanation of Ketones
2091
Table 1. Thiocyanation of ketones with oxone in methanol at room temperature
Entry
a
Substrate
Product
Time (h)a
Yield (%)b
6.0
86
b
c
5.5
6.0
90
82
6.5
89
d
e
f
7.0
5.5
88
86
g
5.0
6.0
88
86
h
i
6.5
6.0
5.0
85
87
j
k
86
(Continued)

2092
M. A. Kumar et al.
Table 1. Continued
Entry
l
Substrate
Product
Time (h)a
Yield (%)b
5.0
5.0
88
m
89
aThe reaction time.
bIsolated yields of products after column chromatography.
k–m, Table 1). The main advantage of this method is that a variety of
ketones having a-hydrogens readily underwent thiocyanation at room
1
temperature. All the products were characterized by H NMR, IR, and
mass spectroscopy and by comparison with known samples.[9–11] IR spec-
trum showed the characteristic peak of -SCN at 2158 cmꢀ1. The scope of
this methodology is demonstrated with respect to various ketones, and
results are presented in Table 1. The effect of various solvents on the thio-
cyanation of ketones was primarily observed by taking acetophenone as
an example. Both the yields and reaction times are listed in Table 2.
In methanol, the reaction took place at room temperature with high con-
version. However, low yields were obtained in solvents such as aceto-
nitrile, tert-butanol, and carbon tetrachloride. Therefore, methanol is
the solvent of choice for the thiocyanation of ketones.
In conclusion, we have described a simple, convenient, and efficient
protocol for the thiocyanation of ketones using oxone as an inexpensive
and readily available oxidant. This method offers advantages such as
mild reaction conditions, operational simplicity and the use of economically
Table 2. Effect of solvent on the thiocyanation of 1a
Solvent
Time (h)a
Yield (%)b
Methanol
Acetonitrile
tert-Butanol
Carbon tetrachloride
6
20
20
24
86
30
40
35
aReaction time.
bIsolated and optimized yields.

a-Thiocyanation of Ketones
2093
viable reagents, which make it a useful and attractive process for the
thiocyanation of ketones.
EXPERIMENTAL
Melting points were recorded on a Buchi R-535 apparatus and are uncor-
rected. IR spectra were recorded on a Perkin-Elmer FT-IR 240-c spectro-
photometer using KBr optics. 1H NMR spectra were recorded on Varian
Unity 200 and Bruker 300 spectrometer in CDCl3 using TMS as internal
standard. Mass spectra were recorded on a Finnigan MAT 1020 mass
spectrometer operating at 70 eV.
Typical Experimental Procedure
A solution of carbonyl compound (1.0 mmol) and ammonium thiocyan-
ate (2.0 mmol) in 10 mL of methanol was treated with oxone (1.2 mmol),
and the resulting mixture was stirred at room temperature until com-
pletion of the reaction as monitored by thin-layer chromatography
(TLC). After completion of reaction, the reaction mixture was filtered
and the filtrate was evaporated under reduced pressure. The resulting
product was purified by column chromatography on silica gel (100–200
mesh, ethyl acetate=hexane) to afford pure a-ketothiocyanate. The
products were characterized by 1H NMR, 13C NMR, IR, and mass
spectroscopy.
Spectral Data for Selected Compounds
1-(4-Hydroxyphenyl)-2-thiocyanato-1-ethanone (Entry 2b)
White solid, mp 160–162ꢁC; 1H NMR (CDCl3, 200 MHz): d 10.14 (s, 1H),
7.83 (d, J ¼ 8.7 Hz, 2H), 6.85 (d, J ¼ 8.7 Hz, 2H), 4.82 (s, 2H);13 C NMR
(CDCl3, 75 MHz): d188.9, 162.7, 129.9, 123.8, 114.5, 111.2, 41.5; IR
(KBr): 3280, 2924, 2166, 1668 cmꢀ1; LCMS: m=z 216 (Mþ þ Na).
1-Phenyl-2-thiocyanato-1-butanone (Entry 2e)
1H NMR (200 MHz, CDCl3): d 7.93 (d, J ¼ 7.3 Hz, 2H), 7.64 (t,
J ¼ 7.3 Hz, 1H), 7.51 (t, J ¼ 7.3 Hz, 2H), 5.03 (t, J ¼ 5.8, 1H), 2.36–
2.10 (m, 2H), 1.05 (t, J ¼ 7.3 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d 194.4, 134.3, 133.8, 129.0, 128.5, 111.3, 55.6, 29.5, 10.0; IR (KBr):
2925, 2159, 1672 cmꢀ1; LCMS: m=z 228 (Mþ þ Na).

2094
M. A. Kumar et al.
5-Chloro-2-thiocyanato-1-indanone (Entry 2i)
ꢁ
1
Light brown solid, mp 116–118 C; H NMR (CDCl3, 300 MHz): d 7.77
(d, J ¼ 7.5 Hz, 1H), 7.50 (s, 1H), 7.45 (d, J ¼ 8.3 Hz, 1H), 4.12 (dd, J1–2
¼
4.5, J1–3 ¼ 8.3 Hz, 1H), 3.81 (dd, J1–2 ¼ 8.3, J1–3 ¼ 18.1 Hz, 1H), 3.38
(dd, J1–2 ¼ 4.5, J1–3 ¼ 18.1 Hz, 1H); IR (KBr): 3020, 2158, 1721,
1215 cmꢀ1. LCMS: m=z 224 (Mþ þ 1).
4-Methyl-1-thiocyanato-2-pentanone (Entry 2k)
1H NMR (CDCl3, 300 MHz): d 4.00 (s, 2H), 2.44 (d, J ¼ 6.7 Hz, 2H),
2.25–2.12 (m, 1H), 0.97 (d, J ¼ 6.7 Hz, 6H); IR (KBr): 3020, 2929,
2159, 1718 cmꢀ1; LCMS: m=z 158.2 (Mþ þ 1).
1-Cyclopropyl-2-thiocyanato-1-ethanone (Entry 2m)
1H NMR (CDCl3, 200 MHz): d 4.17 (s, 2H), 2.10–1.98 (m, 1H), 1.31–1.00
(m, 4H); 13C NMR (CDCl3, 75 MHz,): d 201.1, 111.4, 44.2, 19.7, 12.4; IR
(KBr): 2924, 2157, 1696 cmꢀ1; LCMS: m=z 164 (Mþ þ Na).
ACKNOWLEDGMENTS
The authors thank C. Naga Raju, Sri Venkateswara University, Tirupati,
for helpful discussions and Sophisticated Instruments Facility (SIF),
Indian Institute of Science (IISc), Bangalore, for providing the spectral
data.
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