Efficient conversion of thiols to thiocyanates by in situ generated Ph3P(SCN)2

Article abstract of DOI:10.1016/S0040-4039(02)00421-5

A new, novel, rapid and simple method is described for the one-pot conversion of thiols to thiocyanates by use of in situ generated PPh₃(SCN)₂ at room temperature.

Full text of DOI:10.1016/S0040-4039(02)00421-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3439–3441
Efficient conversion of thiols to thiocyanates by in situ generated
†
Ph3P(SCN)2
Nasser Iranpoor,* Habib Firouzabadi* and Hamid Reza Shaterian
Department of Chemistry, Shiraz University, Shiraz 71454, Iran
Received 5 December 2001; revised 18 February 2002; accepted 28 February 2002
Abstract—A new, novel, rapid and simple method is described for the one-pot conversion of thiols to thiocyanates by use of in
situ generated PPh3(SCN)2 at room temperature. © 2002 Elsevier Science Ltd. All rights reserved.
Thiocyanates are considered as important and valuable
sulfur-containing compounds for the synthesis of hete-
rocycles and have traditionally been used as pesti-
cides.1,2 They are generally prepared via nucleophilic
displacement of leaving groups by thiocyanate ion on a
carbon atom preferably in the presence of phase trans-
fer agents.3–7
In order to optimize the reaction conditions, we first
examined the effect of different ratios of triphenylphos-
phine/bromine/ammonium thiocyanate on the conver-
sion of benzyl thiol to benzyl thiocyanate.
Similar to the reaction of benzyl alcohol, benzyl thiol
reacted with PPh3(SCN)2 immediately at room temper-
ature to give benzyl thiocyanate. In addition to benzyl
thiocyanate, dibenzyl disulfide was formed as a side
product in 20% yield when we used an equimolar ratio
of 1/1/1/2 of benzyl thiol/Ph3P/Br2/NH4SCN (entry 1,
Table 1). In order to avoid the intermolecular coupling
of thiols to disulfides by the electrophilic species20 that
are present in the reaction mixture, we decided to
increase the stoichiometry of Ph3P with respect to
bromine. As shown in Table 1, when the stoichiometry
of PPh3 and ammonium thiocyanate are slightly more
than that of bromine, the oxidation of thiol to disulfide
is minimized and benzyl thiocyanate is obtained in
excellent yield (entries 6 and 7, Table 1).
Mixed reagent systems of tertiary phosphines/halogens
or tertiary phosphines/halogenated compounds have
been widely used for the transformation of alcohols and
also thiols to alkyl halides.8–17 Due to the importance of
the conversion of thiols to other functionalities, very
recently we reported on the application of mixtures of
Ph3P and N-chloro-, N-bromo- and N-iodosuccinimide
for the efficient conversion of thiols to different alkyl
halides.18
In continuation of our work on the use of in situ
generated Ph3P(SCN)2 for the preparation of thio-
cyanates from alcohols,19 we wish to report on the use
of this reagent for the efficient conversion of primary
and secondary alkyl and benzyl thiols to their corre-
sponding thiocyanates at room temperature (Scheme 1).
Ph3P(SCN)2 can be easily produced in situ from the
reaction of Ph3P, bromine and ammonium thio-
cyanate.19 This compound has already been shown to
be in equilibrium with Ph3P+SCN/SCN−.7b
* Corresponding authors. Tel.: +0098-711-2284822; fax: +0098-711-
2280926;
e-mail:
iranpoor@chem.susc.ac.ir;
firouzabadi@
chem.susc.ac.ir
†
This paper is dedicated to our mentor Professor Ali Massoumi on
the occasion of his 70th birthday.
Scheme 1.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00421-5

3440
N. Iranpoor et al. / Tetrahedron Letters 43 (2002) 3439–3441
Table 1. Optimization of the ratio of benzyl thiol/Ph3P/
Br2/NH4SCN for preparation of benzyl thiocyanate at
room temperature
In order to observe the effect of temperature on the
ratio of thiocyanate and isothiocyanate obtained from
secondary thiols, we isolated the crude reaction mix-
ture obtained from the reaction of 1-cyclohexanethiol
with Ph3P(SCN)2 at 25°C. We then heated this mix-
ture to 60°C for 15 min. Analysis of the mixture
obtained did not show any change in the percentage
of the products (RSCN, RNCS) in the reaction mix-
ture. Thus, it can be concluded that isothiocyanates
are not formed by the isomerization of the thio-
cyanates to isothiocyanates and their formation is due
to the ambident nature of the NCS− nucleophile. This
result is in agreement with the reported data in the
literature.7b,21
PhCH2SH“PhCH2SCN+PhCH2SSCH2Ph
A
B
Entry
Sub/Ph3P/Br2/NH4SCN ratio
GC Yield (%)a
A
B
1
2
3
4
5
6
7
1/1/1/2
75
86
91
95
96
20
12
9
1/1.1/1/2
1/1.2/1/2
1/1.2/1/2.2
1/1.2/1/2.3
1/1.3/1/2.5
1/1.5/1/3
5
4
0
0
100
100
In summary, this method is the first report of the
direct conversion of thiols into thiocyanates at room
temperature. The use of in situ generated PPh3(SCN)2
provides the possibility of performing this transforma-
tion under very mild reaction conditions with excel-
lent yield. The procedure is simple, rapid and the
work up is clean and not time-consuming.
a The reaction was completed immediately. Yields are based on GC
analysis using n-heptane as internal standard.
We therefore used the stoichiometric ratio of thiol/
Ph3P/Br2/NH4SCN (1/1.3/1/2.5) for the conversion of
thiols to their corresponding alkyl thiocyanates. The
results are shown in Table 2. The results obtained
show that this reagent is suitable for the immediate
conversion of primary, secondary and benzyl thiols to
their corresponding alkyl thiocyanates in excellent
yields at room temperature.
Experimental
The products were purified by column chromatogra-
phy and the purity determinations of the products
were accomplished by GLC on a Shimadzu model
GC-10A instrument or by TLC on silica-gel polygram
SIL G/UV 254 plates. Mass spectra were run on a
Shimadzu GC MS-QP 1000EX at 75 eV. IR spectra
were recorded on a Perkin–Elmer 781 spectrophoto-
meter. The NMR spectra were recorded on a Bruker
Avance DPX 250 MHz instrument.
Primary thiols produced exclusively the corresponding
thiocyanates, but secondary thiols gave small amounts
of isothiocyanates as side products (Table 1, entries
1–5). On treatment of 1-cyclohexanethiol with this
reagent, 1-cyclohexyl thiocyanate was formed as the
major product (96%) together with the formation of
1-cyclohexyl isothiocyanate (6%, Table 2, entry 6).
The formation of thiocyanates or isothiocyanates can
be easily detected in the reaction mixture by the char-
acteristic 13C absorption band of the -SCN and -NCS
groups at ꢀ111 and ꢀ145 ppm, respectively.22
General procedure for the synthesis of 1 and 2°
thiocyanates from thiols
A three-necked flask equipped with a dropping fun-
nel, stirrer, CaCl2 drying tube and N2 gas inlet was
charged with Ph3P (2.6 mmol) and dry CH3CN (5
mL), then Br2 (2.0 mmol) was added dropwise to the
solution at room temperature under N2 atmosphere.
When the addition was complete, a solution of
NH4SCN (5.0 mmol) in CH3CN (5 mL) was added
dropwise. Upon addition of thiols (2.0 mmol) to the
resulting mixture, spontaneous reactions occurred. To
the resulting mixture, silica gel was added and the
solvent was evaporated on a rotary evaporator. The
resulting solid was applied on a silica gel column and
washed with petroleum ether 60–80°C/EtOAc (9/1) to
give the desired thiocyanate (Table 2).
Table 2. One-pot conversion of thiols to thiocyanates with
Ph3P(SCN)2 at room temperature
Entry
RSH
Yield (%)a
Percentage of the
productb
RSCN
RNCS
1
2
3
4
5
6
PhCH2SH
90
91
87
89
90
87
100
100
100
100
96
0
0
0
0
4
6
CH3(CH2)11SH
CH3(CH2)7SH
CH3(CH2)3SH
CH3CH(SH)CH3
94
Acknowledgements
a Isolated yield. The products were identified by comparison of their
physical data with those reported for known samples6b,7b,22
b The percentage of the products in the reaction mixture was deter-
mined by 1H and 13C NMR22
The authors are grateful to Shiraz University
Research Council for the partial support of this
work.

N. Iranpoor et al. / Tetrahedron Letters 43 (2002) 3439–3441
3441
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