PEG-SO3H as soluble acidic polymeric catalyst for regioselective ring opening of epoxides: A high-efficient synthetic approach to β-hydroxy thiocyanates

Article abstract of DOI:10.1080/00397910802044231

Poly(ethylene glycol)-bound sulfonic acid, PEG-SO3H, was developed as an environmentally friendly and efficient homogeneous polymeric catalyst in organic synthesis. This polymeric phase-transfer catalyst catalyzed the regioselective ring opening of epoxides by thiocyanate ion to give thiocyanohydrins as key intermediates in agricultural and pharmaceutical chemistry in high yields. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802044231

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PEG-SO3H as Soluble Acidic
Polymeric Catalyst for
Regioselective Ring Opening
of Epoxides: A High-Efficient
Synthetic Approach to β-
Hydroxy Thiocyanates
Ali Reza Kiasat a & Mehdi Fallah Mehrjardi a
a Chemistry Department, College of Science, Shahid
Chamran University, Ahvaz, Iran
Version of record first published: 28 Aug 2008.
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Soluble Acidic Polymeric Catalyst for Regioselective Ring Opening of Epoxides: A High-
Efficient Synthetic Approach to β-Hydroxy Thiocyanates, Synthetic Communications:
An International Journal for Rapid Communication of Synthetic Organic Chemistry,
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Synthetic Communications1, 38: 2995–3002, 2008
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910802044231
PEG-SO3H as Soluble Acidic Polymeric
Catalyst for Regioselective Ring Opening of
Epoxides: A High-Efficient Synthetic Approach
to b-Hydroxy Thiocyanates
Ali Reza Kiasat and Mehdi Fallah Mehrjardi
Chemistry Department, College of Science, Shahid Chamran University,
Ahvaz, Iran
Abstract: Poly(ethylene glycol)–bound sulfonic acid, PEG-SO3H, was developed
as an environmentally friendly and efficient homogeneous polymeric catalyst in
organic synthesis. This polymeric phase-transfer catalyst catalyzed the regioselec-
tive ring opening of epoxides by thiocyanate ion to give thiocyanohydrins as key
intermediates in agricultural and pharmaceutical chemistry in high yields.
Keywords: PEG-SO3H, polymer support, regioselectivity, ring opening,
thiocyanohydrine
Soluble polymeric supports offer certain advantages over insoluble poly-
mers in terms of ease of analysis and monitoring and, most importantly,
the establishment of homogeneous conditions, which are most conducive
to bimolecular processes.[1] Polyethylene glycol (PEG) and its derivatives
are known to be inexpensive, thermally stable, recoverable, toxicologi-
cally innocuous, and environmentally benign media for chemical
reactions,[2] as well as having almost negligible vapor pressure.
The formation of thiiranes from the reaction of epoxides and thio-
cyanate has been proposed to occur through the intermediacy of the cor-
responding b-hydroxy thiocyanate, but this intermediate has not been
isolated because of its rapid conversion to the corresponding thiirane.[3]
The presence of some hydroquinone[4] or 2,3-dicyano-5,6-dichloro-1,4
Received October 17, 2007.
Address correspondence to Ali Reza Kiasat, Chemistry Department, Faculty
of Sciences, Shahid Chamran University, Ahvaz 61357-4-3169, Iran. E-mail:
akiasat@scu.ac.ir
2995

2996
A. R. Kiasat and M. F. Mehrjardi
benzoquinone (DDQ)[5] is required to stabilize the produced b-hydroxy
thiocyanate and to inhibit its conversion to thiirane. Although a few use-
ful reagents, such as Ph3P(SCN)2,[6] Ti(O-iPr)4,[7] TiCl3 (or ZnCl2),[8]
Pd(PPh3)4,[9] trimethylsilyl isothiocyanate (TMSNCS) (Cat. tetrabutyl-
ammonium fluoride [TBAF]),[10] crowns, and cryptants[11] have been
reported for the ring opening of epoxide to the thiocyanohydrine, unfor-
tunately some of these methods are not always fully satisfactory and
suffer from disadvantages such as relatively long reaction times or low
regioselectivity, or involve high-temperature reaction conditions to
obtain ring-opened products. Consequently, it seems that there is still a
need for development of newer methods that proceed under mild and
economically appropriate conditions. Recently, applications of some
metalloporphyrins,[12–15] polymeric phase-transfer catalyst,[16] and Select-
fluor[17] as catalysts for regioselective conversion of epoxides to
b-hydroxy thiocyanates were reported.
Keeping in mind these facts, we now describe our successful result
that led to an efficient and simple method for the transformation of
epoxides into the corresponding b-hydroxy thiocyanates using NH4SCN
in the presence of a catalytic amount of poly(ethylene glycol)-bound
sulfonic acid, PEG-SO3H, in high isolated yields.
PEG-SO3H was prepared[18] by simple mixing of PEG-6000 and
chlorosulfonic acid in CH2Cl2 (Scheme 1). The reaction is very clean,
and the polymeric phase-transfer catalyst can be easily precipitated in
ether.
Conversion of terminal hydroxyl groups of PEG to OSO3H is con-
firmed by 1H NMR spectroscopy. The 1H NMR spectrum shows singlets
at d 12.85 and d 4.23 ppm due to the proton of SO3H and the methylene
protons in polymer backbone, respectively.
In the first step, phenyl glycidyl ether was chosen as a model
compound and reacted with NH4SCN in CH2Cl2 and in the presence
of PEG-SO3H. Thin-layer chromatographic (TLC) analysis showed that
the catalyst acted very efficiently, and only 0.1 molar equivalent of the
catalyst was enough to convert phenyl glycidyl ether to its corresponding
b-hydroxy thiocyanate in high isolated yield within 1 h (Table 1).
Different types of oxiranes, except styrene oxide, carrying activated
and deactivated groups were cleanly, easily, and efficiently converted to
the corresponding b-hydroxy thiocyanates as exclusive and virtually pure
1
products according to TLC and H NMR, in considerably short times
Scheme 1. Preparation of poly(ethylene glycol)-bound sulfonic acid.

PEG-SO3H as Soluble Acidic Polymeric Catalyst
2997
Table 1. Reaction of various epoxides with ammonium thiocyanate in the
a
presence of PEG-SO3H in CH2Cl2
Entry
Substrate
Product (s)
Yields (%)
83 (96:4)b
88
1
2
3
91
4
5
88
84
6
7
85
90
aProducts were identified by comparison of their physical and spectral data
with those of authentic samples.
bAccording to GC analysis.
and in high isolated yields. The scope and generality of this process is
illustrated with several examples, and the results are summarized
in Table 1. The structure of all the products were settled from their
1
analytical and spectral (IR, H NMR) data and by direct comparison
with authentic samples.
It is noteworthy that no evidence for the formation of thiirane as
by-product of the reaction was observed, and the products were obtained
in pure form without further purification.

2998
A. R. Kiasat and M. F. Mehrjardi
Scheme 2. Regioselective ring opening of epoxide in the presence of PEG-SO3H.
The reaction of styrene oxide with NH4SCN in the presence of
PEG-SO3H was completed in CH2Cl2 at room temperature after 1 h and
produced 2-hydroxy-1-phenylethyl thiocyanate (II) as the major product
and a trace amount of other regioisomer 2-hydroxy-2-phenylethyl thio-
cyanate (I). Epoxides carrying electron-withdrawing groups reacted under
similar reaction conditions, and their corresponding b-hydroxy thiocya-
nates were produced in excellent yields and regioselectivity. In these cases,
with the attack of the thiocyanate ion on the less substituted oxirane car-
bon, the regioselectivity was reversed and b-hydroxy thiocyanates (I) were
obtained. It is shown that, for epoxides carrying electron-donating groups,
it is the electronic factor that predominates, and the thiocyanate ion attacks
predominantly at the secondary carbon atom of the epoxide ring, a fact that
is reasonably well established.[19] In contrast, in epoxides carrying electron-
withdrawing groups, it is the steric factor in that predominates and the
nucleophilic attack of thiocyanate ion is strongly favored on the less
substituted carbon of epoxides. Also in the case of cyclohexene oxide, the
stereochemistry of the ring-opened product was found to be trans.
The efficiency of PEG-SO3H in the conversion of epoxides to b-hydroxy
thiocyanates was definitely confirmed by reaction of styrene oxide with
NH4SCN under similar reaction conditions, without adding PEG-SO3H.
In this case, the reaction did not complete after 5 h, and only a little thiirane
was obtained. Also this reaction was examined in the presence of PEG
instead of PEG-SO3H. TLC analysis showed that the reaction did not com-
plete after 5 h and only a trace amount of b-hydroxy thiocyanate was
obtained. Any attempts to prepare thiocyanohydrin by ring opening of styr-
ene oxide with thiocyanate anion in the presence of PEG and sulfuric acid
were not successful, and polymerization reaction was occurred.
It seems that this polymeric catalyst forms a complex with cation,
much like crown ethers, and this complex causes the anion to be acti-
vated. In addition, polymeric catalyst probably can be facilitated the ring
opening of the epoxide by hydrogen bonding as shown in Scheme 3.
Compared to some previously reported methods with major or
minor drawbacks, several noteworthy features of this reagent are appa-
rent, such as easily workup procedure, operational simplicities, and use
of inexpensive reagent.

PEG-SO3H as Soluble Acidic Polymeric Catalyst
2999
Scheme 3. Anion activation by PEG-SO3H.
In summary, we believe that the present procedure for regioselective
ring opening of epoxides with ammonium thiocyanate using PEG-SO3H
provides an easy, mild, efficient, versatile, and general methodology for
the preparation of b-hydroxy thiocyanates from different classes of
epoxides, and we feel that it may be a suitable addition to methodologies
already present in the literature.
EXPERIMENTAL
Some 1,2-epoxyalkanes and other chemical materials were purchased
from Fluka and Merck in high purity. Poly(ethylene glycol)–bound sulfo-
nic acid was prepared according to the previously reported procedure.[18]
All of the thiocyanohydrin compounds were prepared by our procedure,
and their spectroscopic and physical data were compared with those of
authentic samples.
NMR spectra were recorded in CDCl3 on a Bruker Advanced DPX
400-MHz instrument spectrometer using TMS as internal standard. IR
spectra were recorded on a BOMEM MB-Series 1998 FT-IR spectrometer.
The purity determination of the products and reaction monitoring were
accomplished by TLC on silica-gel polygram SILG=UV 254 plates.
General Procedure for the Preparation of b-Hydroxy
Thiocyanatesin CH2Cl2
To a mixture of epoxide (1 mmol) and NH4SCN (3 mmol) in CH2Cl2
(10 mL), PEG-SO3H (0.1 mmol, 0.6 g) was added, and the mixture was
stirred at room temperature for 1 h. The progress of the reaction was
monitored by TLC using CCl4-ether (4:1). On completion of the reaction,
the solvent was evaporated under reduced pressure. Water (10 mL) was
added to the residue, and then the product was extracted with ether
(3 ꢀ 10 mL). The solvent was dried over anhydrous calcium chloride

3000
A. R. Kiasat and M. F. Mehrjardi
and evaporated under reduced pressure. The desired thiocyanohydrines
were obtained in good to excellent isolated yields (83–91%).
Representative Examples of Spectra Data of Thiocyanohydrin
3-Phenoxy-2-hydroxypropyl Thiocyanate[14]
1
IR (neat): n SCN (2156 cmꢁ1). H NMR (CDCl3, 400 MHz): d ¼ 7.27
(2H, m), 7.01 (1H, m), 6.9 (1H, m), 4.29 (1H, m), 4.04 (2H, d), 3.78
(1H, s), 3.30 (1H, m), 3.16 (1H, m). 13C NMR (CDCl3, 100 MHz):
d ¼ 158.5, 129.9, 121.3, 114.6, 113.0, 69.5, 68.0, 37.4.
2-Hydroxycyclohexyl Thiocyanate[14,16]
1
IR (neat): n SCN (2151 cmꢁ1). H NMR (CDCl3, 400 MHz): d ¼ 3.34
(1H, m), 3.14 (2H, m), 1.98 (2H, m), 1.69 (2H, m), 1.21–1.28 (4H, m).
13C NMR (CDCl3, 100 MHz): d ¼ 110.5, 76.4, 52.6, 31.5, 30.5,25.1, 22.2.
3-Allyloxy-2-hydroxypropyl Thiocyanate[14]
IR (neat): n SCN (2155cmꢁ1). 1H NMR (CDCl3, 400 MHz): d ¼ 5.86 (1H,
m), 5.19–5.29 (2H, m), 4.05 (3H, m), 3.53 (2H, m), 3.04–3.24 (3H, m).
13C NMR (CDCl3, 100MHz): d ¼ 133.6, 117.4, 113.0, 71.6, 70.7, 69.1, 37.3.
2-Hydroxy-3-thiocyanatopropyl Methacrylate
1
IR (neat): n SCN (2157 cmꢁ1). H NMR (CDCl3, 400 MHz): d ¼ 6.06
(1H, m), 5.55 (1H, m), 4.4 (3H, m), 3.40 (1H, m), 3.16 (1H, m), 3.03
(1H, m), 1.85 (3H, m). 13C NMR (CDCl3, 100 MHz): d ¼ 167.0, 135.2,
126.5, 112.8, 68.0, 66.1, 37.3, 18.4.
ACKNOWLEDGMENT
We gratefully acknowledge the support of this work by the Chamran
University Research Council.
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