Preparation of thiocyanates and isothiocyanates from alcohols, thiols, trimethylsilyl-, and tetrahydropyranyl ethers using triphenylphosphine/2,3-dichloro-5,6-dicyanobenzoquinone (DDQ)/n-Bu4NSCN system

Article abstract of DOI:10.1016/j.tet.2006.03.030

A combination of triphenylphosphine (PPh₃) and 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) provides a safe and easily available mixed reagent system for the conversion of 1° and 2° alcohols, thiols, trimethylsilyl-, and tetrahydropyranyl ethers to their corresponding thiocyanates and the 3° ones to isothiocyanates in good to high yields.

Full text of DOI:10.1016/j.tet.2006.03.030

Tetrahedron 62 (2006) 5498–5501
Preparation of thiocyanates and isothiocyanates from alcohols,
thiols, trimethylsilyl-, and tetrahydropyranyl ethers using
triphenylphosphine/2,3-dichloro-5,6-dicyanobenzoquinone
(DDQ)/n-Bu4NSCN system
*
Nasser Iranpoor, Habib Firouzabadi and Najmeh Nowrouzi
*
Department of Chemistry, College of Sciences, Shiraz University, Shiraz 71454, Iran
Received 6 June 2005; revised 22 February 2006; accepted 10 March 2006
Available online 12 April 2006
Abstract—A combination of triphenylphosphine (PPh3) and 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) provides a safe and easily avail-
able mixed reagent system for the conversion of 1ꢀ and 2ꢀ alcohols, thiols, trimethylsilyl-, and tetrahydropyranyl ethers to their corresponding
thiocyanates and the 3ꢀ ones to isothiocyanates in good to high yields.
Ó 2006 Published by Elsevier Ltd.
1. Introduction
2. Results and discussion
The Mitsunobu reaction has been widely used for the dis-
placement of alcohols by different nucleophiles.1–3 In this
reaction, in which a mixture of triphenylphosphine, diethyl
azodicarboxylate (DEAD), and a nucleophile is used, the
phosphine and the azodicarboxylate accepts the oxygen
and the hydrogen atoms, respectively, to give triphenylphos-
phine oxide and a hydrazine derivative with the consequent
replacement of the hydroxyl group by the nucleophile.
Among these transformations, the conversion of a hydroxyl
group to a thiocyanate functionality is widely used for the
preparation of heterocycles.4,5 Recently, we reported a new
application for the Mitsunobu reaction and studied the re-
action of alcohols, thiols, carboxylic acids, trimethylsilyl
ethers, and carboxylates with PPh3/DEAD/NH4SCN.6
Recently we reported the use of DDQ as a suitable replace-
ment for DEAD for the preparation of alkyl halides, nitriles,
and azides from alcohols.17 Very recently, the use of DDQ
for the preparation of isocyanides from alcohols and thiols
was also reported.18 To reduce the problems encountered
in thiocyanation reactions using the Mitsunobu reagent sys-
tem6 or PPh3(SCN)2,7–9 e.g., DEAD is expensive, is not eas-
ily available, and may explode on heating and the poisonous
PPh3(SCN)2 should be prepared freshly before use, we now
report that the combination of PPh3 and DDQ in the presence
of n-Bu4NSCN, which are readily available solid reagents,
offers a simple and safe method for the conversion of
primary and secondary alcohols as well as thiols, trimethyl-
silyl-, and tetrahydropyranyl ethers into their corresponding
thiocyanates and tertiary systems into their isothiocyanates
in good to high yields (Scheme 1).
Prior to this work, we also reported on the use of in situ
generated PPh3(SCN)2 for the conversion of alcohols,7b
thiols,8 and also trimethylsilyl ethers9 to alkyl thiocyanates.
Apart from the above mentioned methods, the use of
KSCN$CuBr2,10 solid-supported potassium thiocyanate,11
and thiocyanate ion12 preferably in the presence of phase-
transfer agents13–16 are widely used for the preparation of
thiocyanates from alkyl halides.
PPh3, DDQ, n-Bu4NSCN RSCN (R= 1°, 2°)
RX
CH3CN
RNCS (R= 3°)
X= OH, SH, OSiMe3, OTHP
Scheme 1.
We first carried out a comparative study on the possibility
of using different electron-deficient reagents such as
2,3-dichloro-5,6-dicyanobenzoquinone (DDQ), 2,3,5,6-
tetrachlorobenzoquinone (p-chloranil), tetracyanoethylene
(TCNE), tetraphenylcyclopentadienone (tetracyclone), 4-
phenyl-1,2,4-triazoline-3,5-dione (PTAD) as well as diethyl
acetylenedicarboxylate (DEACD) in conjunction with PPh3
Keywords: Thiocyanation; Isothiocyanation; Alcohol; Thiol; Trimethylsilyl
ether; Tetrahydropyranyl ether; Triphenylphosphine; DDQ.
* Corresponding authors. Tel.: +98 711 2287600; fax: +98 711 2280926;
e-mail addresses: iranpoor@chem.susc.ac.ir; firouzabadi@chem.susc.
ac.ir
0040–4020/$ - see front matter Ó 2006 Published by Elsevier Ltd.
doi:10.1016/j.tet.2006.03.030

N. Iranpoor et al. / Tetrahedron 62 (2006) 5498–5501
5499
and n-Bu4NSCN for the conversion of benzyl alcohol to
benzyl thiocyanate as a model reaction. The results obtained
from this study (Table 1) show that the combination of PPh3/
DDQ/n-Bu4NSCN and PPh3/p-chloranil/n-Bu4NSCN pro-
vides the most suitable reagent systems for this transforma-
tion and benzyl thiocyanate was formed in quantitative
yield. Of these two reagent systems, the use of DDQ provides
a much shorter reaction time (almost immediately) compared
to using p-chloranil (8 h). The combination of PPh3/DEAD/
n-Bu4NSCN produced only 20% of benzyl thiocyanate after
24 h and other reagent systems none. As we reported
already,6 this reaction occurs using the combination of
DEAD, PPh3, and NH4SCN. However, apart from the prob-
lems encountered using DEAD, ammonia is also produced
in the reaction, which could be harmful to some base-sensi-
tive functional groups.
Table 2. In these reactions, thiocyanates were obtained in
high yield without the formation of any disulfides through
the dimerization of thiols.
Trimethylsilyl- and tetrahydropyranyl ethers are popular
forms of protected hydroxyl groups, which are practical
precursors for the preparation of many other compounds
and their controlled transformation to other functional
groups has been considered as an interesting goal in organic
synthesis.22,23
Table 2. Conversion of alcohols and thiols to alkyl thiocyanates or isothio-
cyanates
Entry
RX
RSCN/
RNCSa
Time
Isolated yield
% (ref)
OH
1
2
100/0
74/26
5 min
90 (19a)
88b (20)
Table 1. Conversion of benzyl alcohol to benzyl thiocyanate using
n-Bu4NSCN in the presence of Ph3P and different reagents in acetonitrile
at room temperature
15 min
OH
OH
Entry
Reagenta
Time (h)
Conversion %b
1
2
3
4
5
6
7
DDQ
p-Chloranil
DEAD
DEACD
TCNE
<1 min
8
24
24
24
100
100
20
0
0
0
3
4
100/0
100/0
<1 min
<1 min
95 (7b)
92 (7b)
OH
Tetracyclone
PTAD
24
24
0
OH
a
5
6
100/0
100/0
<1 min
<1 min
92 (7b)
90 (19)
The stoichiometric ratio of PPh3/DDQ/n-Bu4NSCN/ROH is 2:2:2:1.
GC yield using an internal standard.
H3CO
O2N
b
OH
We also used NH4SCN instead of n-Bu4NSCN but the reac-
tion did not finished after 24 h and benzyl thiocyanate was
formed only in 30% yield.
OH
7
8
9
61/39
100/0
60/10
<1 min
<1 min
<1 min
94b (7b)
90 (7b)
The order of addition of reagents is also very important. The
mixture of PPh3 and DDQ is first prepared in acetonitrile and
n-Bu4NSCN is added to this mixture followed by the addi-
tion of alcohol.
OH
Using this method, primary alcohols are converted to their
corresponding alkyl thiocyanates without the formation of
any isothiocyanates, but secondary alcohols give also some
minor amounts of isothiocyanates as a side-product. In the
case of a tertiary alcohol, the isothiocyanate is formed as
the major product together with small amounts of eliminated
product.
OH
OH
55b,c (19)
10
11
82/18
0/80
75 min
20 h
92b (7b)
13C resonance of the –SCN and –NCS groups atw111 and
w145 ppm, respectively, are very characteristic for thiocya-
nate and isothiocyanate functionalities.7b,9,19 The formation
of isothiocyanates does not occur through the isomerization
of the corresponding thiocyanates since, when we heated
the crude reaction mixture obtained from the reaction of
1-phenylpropanol at 25 ꢀC to 60–70 ꢀC, no change in the
distribution of the isomeric products (RSCN, RNCS) was
observed. Thus, their formation is due to the ambident
nature of the NCSÀ nucleophile and this is in agreement
with the reported data in the literature.20,21 Lowering the
reaction temperature from 25 to 0 ꢀC had also no significant
effect on this distribution.
Me
C
68c,d (19)
OH
Me
SH
12
13
100/0
100/0
45 min
1 h
90 (7b)
87 (19a)
SH
SH
14
80/20
90 min
90b (7b)
a
GC and NMR yield using an internal standard.
b
c
d
Mixture of thiocyanate and isothiocyanate was obtained.
Eliminated product (15–20%) was also produced.
This reaction was performed under reflux.
We then applied this method for the conversion of thiols to
their corresponding thiocyanates. The results are shown in

5500
N. Iranpoor et al. / Tetrahedron 62 (2006) 5498–5501
Trimethylsilyl- and tetrahydropyranyl ethers reacted effi-
ciently with the same mixed reagent system and produced
the corresponding thiocyanates or isothiocyanates in high
yields. The results are shown in Table 3.
son of their spectral data with those of known com-
pounds.7b,9,19 FTIR spectra were recorded on a Shimadzu
DR-8001 spectrometer. NMR spectra were recorded on
a Brucker Avance DPX 250 MHz instrument. Mass spectra
were recorded on a Shimadzu GC–MS-QP 1000PX.
Table 3. Conversion of silyl- and THP-ethers to thiocyanates or isothiocya-
nates in acetonitrilea
3.1. Typical procedure for the conversion of benzyl
alcohol to benzyl thiocyanate
Entry
RX
RSCN/
RNCSb
Time
Isolated
yield %
A mixture of DDQ (2.0 mmol, 0.454 g) and PPh3 (2.0 mmol,
0.524 g) in dry CH3CN (5 ml), was stirred at room temper-
ature for 5 min. Then, n-Bu4NSCN (2.0 mmol, 0.6 g) was
added and while the reaction mixture was stirring, benzyl
alcohol (1.0 mmol, 0.108 g) was added. GC analysis showed
the immediate completion of the reaction. The solvent was
evaporated. Column chromatography of the crude mixture
on silica-gel using n-hexane–ethyl acetate (3:1) as eluent
gave benzyl thiocyanate as pale yellow crystals, 0.134 g,
95% yield (mp 40 ꢀC, lit.19a mp 39–40 ꢀC). IR (–SCN):
OSiMe3
1
2
100/0
100/0
<1 min
<1 min
91
93
OSiMe3
OSiMe3
3
4
78/22
0/80
10 min
24 h
90
1
2155 cmÀ1; H NMR (CDCl3): d (ppm) 7.3 (5H, s), 4.1
Me
(2H, s); 13C NMR (CDCl3): d (ppm) 134.8, 132.6, 129.6,
129.4, 112.2, 38.7.
72c,d
C OSiMe3
Me
OTHP
3.2. Typical procedure for the conversion of trimethyl-
(1-phenyl-propoxy)-silane to (1-thiocyanato-propyl)-
benzene
5
6
100/0
100/0
13 h
15 h
92
88
OTHP
To a flask containing a stirring mixture of DDQ (2.0 mmol,
0.454 g) and PPh3 (2.0 mmol, 0.524 g) in dry CH3CN (5 ml),
was added n-Bu4NSCN (2.0 mmol, 0.6 g) at room tempera-
ture. Then, trimethyl-(1-phenyl-propoxy)-silane (1 mmol,
0.2 g) was added to the mixture. The progress of the reaction
was followed by GC. After completion of the reaction, sol-
vent was evaporated. Column chromatography of the crude
mixture on silica-gel using n-hexane–ethyl acetate (3:1) as
eluent gave (1-thiocyanato-propyl)-benzene (Table 3, entry
3) as the main product with 75% yield. IR (–SCN):
OTHP
7
77/23
0/85
20 h
40 h
90
Me
8
78c
C OTHP
Me
a
The reactions of silyl ethers were performed at room temperature and
THP-ethers under reflux conditions.
GC and NMR yield using an internal standard.
Eliminated products are also produced.
Reflux condition.
1
2160 cmÀ1; H NMR (CDCl3): d (ppm) 0.96 (3H, t), 2.1
b
c
d
(2H, m), 4.6 (1H, t), 7.2–7.4 (5H, m); 13C NMR (CDCl3):
d (ppm) 137.1, 127.8, 127.7, 124.7, 111.9, 54.2, 31.3, 11.1.
Similar to the reaction of alcohols and thiols, primary silyl-
and tetrahydropyranyl ethers produced exclusively the cor-
responding thiocyanates. In the case of secondary alcohols
and thiols, thiocyanates were also formed as the major
products together with minor amounts of the corresponding
isothiocyanates, however, tertiary systems produced only
isothiocyanates and small amounts of the eliminated
product.
3.3. Typical procedure for the conversion of
2-(1-biphenyl-4-yl-ethoxy)-tetrahydro-pyran to
4-(1-isothiocyanato-1-methyl-ethyl)-biphenyl
To a refluxing solution of PPh3 (2 mmol, 0.524 g), DDQ
(2 mmol, 0.454 g), and n-Bu4NSCN (2 mmol, 0.6 g) in dry
CH3CN (5 ml) was added 2-(1-biphenyl-4-yl-ethoxy)-tetra-
hydro-pyran (1 mmol, 0.296 g). After 40 h, the solvent was
evaporated. Column chromatography on silica-gel using
n-hexane–ethyl acetate (3:1) as eluent gave 4-(1-isothiocya-
nato-1-methyl-ethyl)-biphenyl(Table 3, entry8)in78%yield.
In conclusion, the use of DDQ instead of DEAD in conjunc-
tion with PPh3 and n-Bu4NSCN as safe, available, and easy
handling reagents offers a simple, novel, and convenient
method for the conversion of wide varieties of alcohols,
thiols, trimethylsilyl-, and tetrahydropyranyl ethers to their
corresponding thiocyanates or isothiocyanates.
IR (–NCS): 2085 cmÀ1; 1H NMR (CDCl3): d (ppm) 1.8 (6H,
s), 7.1 (2H, d), 7.5 (5H, m), 8.3 (2H, d); 13C NMR (CDCl3):
d (ppm) 158.9, 145.9, 138.1, 132.2, 130.8, 129.7, 128.2,
124.9, 120.8, 56.0, 19.9.
3. Experimental
Acknowledgements
All the solvents and reagents were purchased from Fluka or
Merck chemical Companies. The products were purified by
column or prep. TLC techniques and identified by compari-
We are thankful to the Organization of Management and
Planning of Iran and Shiraz University Research Council
for the support of this work.

N. Iranpoor et al. / Tetrahedron 62 (2006) 5498–5501
5501
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