Catalyst-free, efficient, and facile conversion of epoxides to -hydroxy thiocyanates under neutral conditions

Article abstract of DOI:10.1080/00397910802578626

Epoxides are efficiently and easily converted to their corresponding -hydroxy thiocyanates by NH4SCN in refluxing acetonitrile in a regio- and chemoselective manner under neutral conditions without using a catalyst, in spite of the use of many different c

Full text of DOI:10.1080/00397910802578626

This article was downloaded by: [North Dakota State University]
On: 15 August 2013, At: 14:31
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Catalyst-Free, Efficient, and
Facile Conversion of Epoxides
to β-Hydroxy Thiocyanates
Under Neutral Conditions
Ghasem Aghapour a & Razieh Hatefipour a
a School of Chemistry, Damghan University of Basic
Sciences, Damghan, Iran
Published online: 15 Apr 2009.
To cite this article: Ghasem Aghapour & Razieh Hatefipour (2009) Catalyst-Free,
Efficient, and Facile Conversion of Epoxides to β-Hydroxy Thiocyanates Under
Neutral Conditions, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 39:10, 1698-1707
To link to this article: http://dx.doi.org/10.1080/00397910802578626
PLEASE SCROLL DOWN FOR ARTICLE
Taylor & Francis makes every effort to ensure the accuracy of all the
information (the “Content”) contained in the publications on our platform.
However, Taylor & Francis, our agents, and our licensors make no
representations or warranties whatsoever as to the accuracy, completeness,
or suitability for any purpose of the Content. Any opinions and views
expressed in this publication are the opinions and views of the authors, and
are not the views of or endorsed by Taylor & Francis. The accuracy of the
Content should not be relied upon and should be independently verified with
primary sources of information. Taylor and Francis shall not be liable for any

losses, actions, claims, proceedings, demands, costs, expenses, damages,
and other liabilities whatsoever or howsoever caused arising directly or
indirectly in connection with, in relation to or arising out of the use of the
Content.
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,
sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden. Terms & Conditions of access and use can be found at
http://www.tandfonline.com/page/terms-and-conditions

Synthetic Communications1, 39: 1698–1707, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802578626
Catalyst-Free, Efficient, and Facile Conversion of
Epoxides to b-Hydroxy Thiocyanates Under
Neutral Conditions
Ghasem Aghapour and Razieh Hatefipour
School of Chemistry, Damghan University of Basic Sciences,
Damghan, Iran
Abstract: Epoxides are efficiently and easily converted to their corresponding
b-hydroxy thiocyanates by NH4SCN in refluxing acetonitrile in a regio- and
chemoselective manner under neutral conditions without using a catalyst, in spite
of the use of many different catalysts reported in the literature for this purpose.
Keywords: Catalyst-free, epoxide, b-hydroxy thiocyanate
Epoxides are important intermediates in organic synthesis.[1] Their facile
regio- and stereoselective ring-opening reactions with a wide variety of
nucleophiles provide a powerful strategy in organic chemistry.[1–6] How-
ever, in most of the epoxide ring-opening reactions under acidic condi-
tions, the formation of a mixture of regio-isomers and polymerization
is observed. On the other hand, thiocyanates have gained considerable
importance in various areas of organosulfur chemistry.[7] For example,
the thiocyanato group occurs as an important functionality in certain
anticancer natural products formed by deglycosylation of glucosinolates
derived from cruciferous vegetables.[8,9] In this connection, b-hydroxy
thiocyanates are also important intermediates in agricultural and phar-
maceutical chemistry. These compounds represent an interesting subclass
and have multiple modes of reactivity. Thus, the development of simple
Received September 6, 2008.
Address correspondence to Ghasem Aghapour, School of Chemistry,
Damghan University of Basic Sciences, Damghan 3671641167, Iran. E-mail: Gh_
Aghapour@dubs.ac.ir
1698

Epoxides to b-Hydroxy Thiocyanates
1699
and efficient methods for the preparation of b-hydroxy thiocyanates,
especially from epoxides, is desirable.
Several methods have been reported for the preparation of
b-hydroxy thiocyanates using different reagents or catalysts. In one
method, thiocyanohydrins are prepared by the opening of a cyclic sulfate
with NH4SCN to form the corresponding b-sulfate, which is hydrolyzed
to the thiocyanohydrin. A second method involves the addition of
thiocyanic acid (generated in situ at low temperature) to the epoxide.[10]
It has been reported for these syntheses that the presence of some DDQ
(2,3-dichloro-5,6-dicyanobenzoquinone) or hydroquinone (benzene-
1,4-diol) is required to stabilize the produced b-hydroxy thiocyanate
and to inhibit its conversion to thiirane.[11] Also, reagents such as
Ti(OiPr)4,[12] triphenylphosphine–thiocyanogen (TPPT),[13] TiCl3,[14]
and Pd(PPh3)4[15] have been introduced for the conversion of specific oxi-
ranes to b-hydroxy thiocyanates using the SCN- anion. In addition, the
conversion of epoxides to b-hydroxy thiocyanates has been carried out
using ammonium thiocyanate in the presence of thioxanthenone-fused
[18]
azacrown ethers,[16] metalloporphyrins,[17] SbCl3, and selectfluor.[19]
Recently, Bellomo and Gonzalez have reported the ring opening of a
specific vinyl epoxide with ammonium or potassium thiocyanate from its
allylic position, affording to its corresponding thiocyanohydrin in the
absence of a catalyst and at room temperature.[20] Herein, in continuation
of our work on the ring opening of epoxides by halide anions producing
b-halohydrins,[21] we now report that also the conversion of simple other
epoxides to their corresponding b-hydroxy thiocyanates does not require
to a catalyst and is easily and efficiently carried out using merely ammo-
nium thiocyanate in refluxing acetonitrile under neutral conditions in a
regio- and chemoselective manner (Scheme 1).
First, we took 1,2-epoxytetradecane as an example and optimized the
reaction conditions for its catalyst-free conversion to 2-hydroxytetradecyl
thiocyanate 1 using NH4SCN. The results are shown in Table 1. As
shown in this table, this conversion was unsuccessful under solvent-free
conditions at room temperature even via grinding of reactants using
2.4 equivalents of NH4SCN (Table 1, entries 1 and 2). In the same con-
ditions, the yield of this reaction was not much improved by increasing
Scheme 1. Catalyst-free conversion of epoxides to b-hydroxy thiocyanates using
NH4SCN in refluxing acetonitrile under neutral conditions.

1700
G. Aghapour and R. Hatefipour
Table 1. Catalyst-free conversion of 1,2-epoxytetradecane to 2-hydroxytetradecyl
thiocyanate 1 using NH4SCN in different conditions
Entry
Solvent
Molar ratioa
Temperature (ꢀC)
Time (h)
Yield (%)
1
2
3
4
5
6
7
8
9
10
—
—
—
—
1:1.2
1:2.4
1:1.2
1:2.4
1:2.4
1:2.4
1:2.4
1:1.2
1:2
rt
rt
80
80
rt
Reflux
rt
Reflux
Reflux
Reflux
28
2
2
0
30b
40c,d
50c,d
10
30
70
60
80
2
CH2Cl2
CH2Cl2
CH3CN
CH3CN
CH3CN
CH3CN
25
25
25
19
16
1.5
1:2.4
91
aMolar ratio is related to epoxide: NH4SCN.
bThe reactants were ground in a glass test tube.
cThe reaction was not clean, and a mixture of undesired other products was
formed in this case.
dThis reaction was performed in an oil bath.
reaction temperature (Table 1, entries 3 and 4). Also, this reaction was
unsuccessful in CH2Cl2 as solvent. In this case, the desired product was
obtained in merely 10–30% yield after 25 h at room temperature or under
reflux conditions (Table 1, entries 5 and 6). Using CH3CN as solvent
instead of CH2Cl2 caused the improvement of the reaction so that 1
was produced in good yield at room temperature after 25 h (Table 1,
entry 7). This reaction afforded better results in CH3CN under reflux
conditions, and finally the best result was obtained in this reaction con-
dition with 2.4 equivalents of NH4SCN so that 2-hydroxytetradecyl thio-
cyanate 1 was produced in 91% yield after only 1.5 h (Table 1, entry 10).
We therefore used this catalyst-free method (Table 1, entry 10) for the
conversion of other epoxides to their corresponding b-hydroxy thiocya-
nates. The results are shown in Table 2. As shown in this table, epoxides
are efficiently converted to b-hydroxy thiocyanates by NH4SCN in reflux-
ing acetonitrile without using a catalyst under neutral conditions. Except
for the case of styrene oxide, which produced two regio-isomers in a
regioselective manner in contrast to the literature[16,17,19] (Table 2,
entry 3), the reaction of other unsymmetrical epoxides occurred with high

Epoxides to b-Hydroxy Thiocyanates
1701
regioselectivity, and the thiocyanate anion attacked at the less-hindered
side of the epoxide ring because of the combination of steric and electronic
factors.
Under these reaction conditions, the ethereal bonds, ester groups,
phenyl ring, carbon–halogen bonds, and carbon–carbon double bonds
as functional groups that are present in the epoxide molecules remained
intact.
In conclusion, the present investigation has demonstrated that the
use of NH4SCN in refluxing acetonitrile without a catalyst offers an easy
and efficient method for the conversion of wide varieties of epoxides to
their corresponding b-hydroxy thiocyanates under neutral conditions.
This method can be efficiently used for the preparation of b-hydroxy
thiocyanates even in the presence of some other functional groups with
excellent chemoselectivity. Excellent yields, easy workup, reduced pollu-
tion, and excellent regioselectivity are considered as other advantages of
this new method.
EXPERIMENTAL
Solvents, reagents, and chemicals were obtained from Merck (Germany)
and Fluka (Switzerland) chemical companies. Products are known com-
pounds[14,16,17,22] and were characterized by comparison of their physical
or spectral data with those prepared according to literature procedures.
Fourier transform–infrared (FT-IR) spectra were recorded on a Perkin-
Elmer RXI spectrophotometer. Nuclear magnetic resonance (NMR)
spectra were recorded on a Brucker Avance DRX-500 spectrometer.
Thin-layer chromatography (TLC) was carried out on silica-gel 254 ana-
lytical sheets obtained from Fluka.
Typical Procedure for the Catalyst-Free Conversion of 1-Chloro-2,3-
epoxypropane to 3-Chloro-2-hydroxypropyl Thiocyanate (8)
1-Chloro-2,3-epoxypropane (0.078 ml, 1 mmol) was added to a flask
containing NH4SCN (0.18 g, 2.4 mmol) in refluxing acetonitrile (10 ml).
The reflux was continued for 2.5 h until TLC showed the completion
of the reaction. After evaporation of solvent, the crude mixture
was subjected to short column chromatography on silica gel 60
(0.063–0.200 mm) using petroleum benzine–ethyl acetate (60:1) to give
1
3-chloro-2-hydroxypropyl thiocyanate 8, 0.136 g, 90% yield. H NMR
(CDCl3, 500 MHz): d 2.86 (s, br, 1H), 3.09–3.13 (dd, 1H, J ¼ 14, 7 Hz),
3.20–3.24 (dd, 1H, J ¼ 14, 5 Hz), 3.68–3.75 (m, 2H), 4.18–4.22 (m, 1H)

1702

1703

1704
G. Aghapour and R. Hatefipour
ppm; 13C NMR (CDCl3, 125.77 MHz): d 37.66, 47.59, 70.29, 112.35 ppm;
FT-IR (neat): 3435 (br), 2918 (s), 2850 (m), 2157 (s), 1072 (s), 771 (s), 694
(w), 567 (w) cmꢁ1
.
Data
2-Hydroxy-3-isopropyloxypropyl Thiocyanate (5)
Yield 97%; oil; 1H NMR (CDCl3, 500 MHz): d 1.20–1.21 (d, 6H,
J ¼ 6.1 Hz), 2.83 (br, 1H), 3.10–3.14 (dd, 1H, J ¼ 13.28, 7.11 Hz), 3.19–
3.22 (dd, 1H, J ¼ 13.28, 4.87 Hz), 3.52–3.55 (dd, 1H, J ¼ 9.5, 5.3 Hz),
3.58–3.61 (dd, 1H, J ¼ 9.5, 4.1 Hz), 3.64–3.69 (m, 1H), 4.08 (m, 1H)
ppm; 13C NMR (CDCl3, 125.77 MHz): d 22.34, 37.73, 69.82, 72.98,
73.03, 112.97 ppm; FT-IR (neat): 3446 (br), 2973 (s), 2918 (s), 2872 (s),
2156 (s), 1128 (s), 1092 (s), 925 (w), 822 (w) cmꢁ1
.
2-Hydroxytetradecyl Thiocyanate (1)
Yield 91%; oil; 1H NMR (CDCl3, 500 MHz): d 0.85–0.88 (t, 3H,
J ¼ 7 Hz), 1.24–1.47 (m, 20H), 1.54–1.58 (m, 2H), 2.29 (br, 1H), 2.89–
2.93 (dd, 1H, J ¼ 13.2, 8.1 Hz), 3.14–3.17 (dd, 1H, J ¼ 13.2, 3.4 Hz),
3.91 (m, 1H) ppm; 13C NMR (CDCl3, 125.77 MHz): d 14.57, 23.12,
25.93, 29.78, 29.84, 29.92, 29.97, 30.06, 30.07, 30.09, 32.35, 36.37,
41.56, 70.72, 113.05 ppm; FT-IR (neat): 3435 (br), 2924 (s), 2853 (s),
2156 (m), 1466 (m), 721 (w) cmꢁ1; mass spectra m=e: 271 (M, 1.5%),
253 (M–H2O, 1%), 194 (M–H2O–HSCN, 20%).
2-Hydroxy-1-phenylethyl Thiocyanate (3)
1
Yield 56%; oil; H NMR (CDCl3, 500 MHz): d 4.08–4.16 (m, 2H), 4.48–
4.51 (t, 1H, J ¼ 6.8 Hz), 7.36–7.41 (m, 5H) ppm; 13C NMR (CDCl3,
125.77 MHz): d 55.47, 65.12, 112.00, 128.39, 129.67, 129.75, 136.08 ppm.
3-Allyloxy-2-hydroxypropyl Thiocyanate (6)
Yield 96%; oil; 1H NMR (CDCl3, 500 MHz): d 3.07–3.12 (dd, 1H,
J ¼ 13.29, 7.38 Hz), 3.19–3.23 (dd, 1H, J ¼ 13.35, 4.53 Hz), 3.33 (br,
1H), 3.53–3.59 (m, 2H), 4.04-4.05 (d, 2H, J ¼ 5.7 Hz), 4.08–4.12 (m,
1H), 5.22–5.25 (d, 1H, J ¼ 10.37 Hz), 5.28–5.31 (d, 1H, J ¼ 17.25 Hz),
5.86–5.94 (m, 1H) ppm; 13C NMR (CDCl3, 125.77 MHz): d 37.74,

Epoxides to b-Hydroxy Thiocyanates
1705
69.48, 71.98, 72.84, 113.19, 118.37, 134.35 ppm; FT-IR (neat): 3448 (br),
3082 (w), 3014 (w), 2918 (s), 2851 (s), 2156 (s), 1647 (w), 1420 (m), 1110
(s), 933 (m), 771 (m) cmꢁ1
.
trans-2-Hydroxycyclohexyl Thiocyanate (7)
1
Yield 95%; oil; H NMR (CDCl3, 500 MHz): d 1.30–1.40 (m, 3H), 1.66–
1.74 (m, 1H), 1.81–1.82 (m, 2H), 2.15–2.19 (m, 1H), 2.27–2.29 (m, 1H),
2.93–2.99 (m, 1H), 3.11 (br, 1H), 3.54–3.59 (m, 1H) ppm; 13C NMR
(CDCl3, 125.77 MHz): d 24.47, 26.30, 33.27, 35.60, 55.61, 73.08,
111.74 ppm; FT-IR (neat): 3420 (br), 2928 (s), 2857 (s), 2152 (m), 1449
(m), 1069 (m), 958 (m), 770 (w), 719 (w) cmꢁ1
.
2-Hydroxy-3-phenoxypropyl Thiocyanate (9)
1
Yield 98%; oil; H NMR (CDCl3, 500 MHz): d 2.62 (br, 1H), 3.16–3.20
(dd, 1H, J ¼ 13.8, 7.0 Hz), 3.27–3.31 (dd, 1H, J ¼ 13.8, 4.6 Hz), 4.05–
4.10 (m, 2H), 4.31–4.35 (m, 1H), 6.91–7.34 (m, 5H) ppm; FT-IR (neat):
3445 (br), 3062 (w), 3040 (w), 2918 (s), 2849 (m), 2156 (s), 1598 (s),
1588 (s), 1495 (s), 1243 (s), 1045 (m), 755 (s), 691 (m) cmꢁ1
.
3-(4-Chlorophenoxy)-2-hydroxypropyl Thiocyanate (10)
Yield 97%; oil; FT-IR (neat): 3446 (br), 3103 (w), 3073 (w), 2926 (m),
2877 (w), 2156 (m), 1596 (m), 1582 (w), 1492 (s), 1243 (s), 1040 (m),
824 (m), 669 (w), 508 (w) cmꢁ1
.
ACKNOWLEDGMENT
We gratefully acknowledge the support of this work by the Damghan
University of Basic Sciences Research Council.
REFERENCES
1. Behrens, C. H.; Ko, S. Y.; Sharpless, K. B.; Walker, F. J. Selective
transformation of 2,3-epoxy alcohols and related derivatives: Strategies for
nucleophilic attack at carbon-1. J. Org. Chem. 1985, 50, 5687–5696.
2. Nugent, W. A. Chiral Lewis acid catalysis: Enantioselective addition of azide
to meso epoxides. J. Am. Chem. Soc. 1992, 114, 2768–2769.

1706
G. Aghapour and R. Hatefipour
3. Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E. N. Asymmetric
catalysis with water: Efficient kinetic resolution of terminal epoxides by
means of catalytic hydrolysis. Science 1997, 277, 936–938.
4. Bonini, C. R.; Righi, G. Regio- and chemoselective synthesis of halohydrins
by cleavage of oxiranes with metal halides. Synthesis 1994, 225–238.
5. Smith, J. G. Synthetically useful reactions of epoxides. Synthesis 1984,
629–656.
6. Yamada, J.; Yumoto, M.; Yamamoto, Y. Aminolead compounds as a new
reagent for regioselective ring opening of epoxides. Tetrahedron Lett. 1989,
30, 4255–4258.
7. Guy, R. G. In The Chemistry of the Cyanates and Their Thio Derivatives; S.
Patai (Ed.); Wiley Interscience: New York, 1977.
8. Shahidi, F. Sulphur Compounds in Foods; C. J. Mussinan, M. E. Keelan (Eds.)
American Chemical Society: Washington, DC, 1994.
9. Mehta, R. G.; Liu, J.; Constantinou, A.; Thomas, C. F.; Hawthorne, M.;
You, M.; Gerhaeuser, C.; Pezzuto, J. M.; Moon, R. C.; Moriarty, R. M.
Cancer chemopreventive activity of brassinin, a phytoalexin from cabbage.
Carcinogenesis 1995, 16, 399–404.
10. (a) Gao, Y.; Sharpless, K. B. Vicinal diol cyclic sulfates: Like epoxides only
more reactive. J. Am. Chem. Soc. 1988, 110, 7538–7539; (b) Van Tamelen, E.
E. The formation and ring-opening of alkene sulfides. J. Am. Chem. Soc.
1951, 73, 3444–3448; (c) Kawashima, K.; Ishiguro, T. On the reactions of
dibenz[b,f]oxireno[d]azepine derivatives. Chem. Pharm. Bull. 1978, 26,
951–955.
11. (a) Iranpoor, N.; Kohmareh, G. A. DDQ Catalyses the conversion of epox-
ides to hydroxy thiocyanates with NH4SCN. Phosphorus, Sulfur Silicon Relat.
¨
Elem. 1999, 152, 135–139; (b) Wagner-Jauregg, G. Athylen-rhodanhydrin.
Liebigs Ann. Chem. 1949, 561, 87–98.
12. Najera, C.; Sansano, J. M. b,d-Epoxy sulfones in organic synthesis, part 2:
Preparation of b,d-bifunctionalized sulfones. Tetrahedron 1991, 47,
5193–5202.
13. Tamura, Y.; Kawasaki, T.; Yasuda, H.; Gohda, N.; Kita, Y. Reaction of
epoxides with triphenylphosphine-thiocyanogen (TPPT): Preparation of
a-thiocyanatovinyl ketones, vic-dithiocyanates, and vic-dithiocyanatohydrins.
J. Chem. Soc. Perkin Trans. 1 1981, 1577–1581.
14. Olszewski, A.; Gros, P.; Fort, Y. Selective ring-opening of x-epoxyalkyl
(meth)acrylates: An efficient access to bifunctional monomers. Tetrahedron
Lett. 1997, 38, 8699–8702.
15. Choudary, B. M.; Rani, S. S.; Kantam, M. L. Selective nucleophilic openings
of 2,3-Epoxy alcohols catalysed by pd(pph3)4. Synth. Commun. 1990, 20,
2313–2317.
16. Sharghi, H.; Salimi Beni, A. R.; Khalifeh, R. Synthesis of some novel
thioxanthenone-fused azacrown ethers, and their use as new catalysts in
the efficient, mild, and regioselective conversion of epoxides to b-hydroxy
thiocyanates with ammonium thiocyanate. Helv. Chim. Acta 2007, 90,
1373–1385.

Epoxides to b-Hydroxy Thiocyanates
1707
17. Sharghi, H.; Hassani Nejad, A. R.; Nasseri, M. A. Metalloporphyrins as new
catalysts in the mild, efficient, and regioselective conversion of epoxides to
b-hydroxy thiocyanates with NH4SCN. New J. Chem. 2004, 28, 946–951.
18. Sawant, S.; Youssef, D.; Mayer, A.; Sylvester, P.; Wali, V.; Arant, M.; El
Sayed, K. Anticancer and anti-inflammatory sulfur-containing semisynthetic
derivatives of sarcophine. Chem. Pharm. Bull. 2006, 54, 1119–1123.
19. Yadav, J. S.; Reddy, B. V. S.; Reddy, C. S. SelectfluorTM: A novel and
efficient reagent for the synthesis of b-hydroxy thiocyanates. Tetrahedron
Lett. 2004, 45, 1291–1293.
20. Bellomo, A.; Gonzalez, D. Diasterodivergent synthesis of optically pure
vinyl episulfides and b-hydroxy thiocyanates from a bacterial metabolite.
Tetrahedron Lett. 2007, 48, 3047–3051.
21. Iranpoor, N.; Firouzabadi, H.; Aghapour, G.; Nahid, A. Selective conversion
of epoxides to vic-halo alcohols and symmetrical or unsymmetrical dihalides
by triphenylphosphine=2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in
the presence of quaternary ammonium halides. Bull. Chem. Soc. Jpn. 2004,
77, 1885–1891.
22. Łukowska, E.; Plenkiewicz, J. Lipase-catalyzed enantiomeric separation of
1-aryloxy-3-thiocyanatopropan-2-ols: An attempt to prepare optically active
thiiranes. Tetrahedron: Asymmetry 2005, 16, 2149–2156.