Biodegradable choline hydroxide promoted environmentally benign thiolysis of epoxides

Article abstract of DOI:10.1016/j.tetlet.2015.12.080

An environmentally benign and rapid thiolysis of epoxides using a biodegradable, choline-based task-specific ionic liquid has been developed. The ring opening reaction of aryl and alkyl epoxides proceeded rapidly and afforded the corresponding β-hydroxysulfides in high yields with excellent regioselectivity. The protocol has the advantages of easy work-up, short reaction times, high yields, and a biodegradable catalyst.

Full text of DOI:10.1016/j.tetlet.2015.12.080

Accepted Manuscript
Biodegradable choline hydroxide promoted environmentally benign thiolysis of
epoxides
Najmedin Azizi, Mahtab Edrisi
PII:
S0040-4039(15)30495-0
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.12.080
TETL 47127
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Revised Date:
Accepted Date:
20 July 2015
10 December 2015
18 December 2015
Please cite this article as: Azizi, N., Edrisi, M., Biodegradable choline hydroxide promoted environmentally benign
thiolysis of epoxides, Tetrahedron Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.2015.12.080
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Graphical Abstract
Biodegradable choline hydroxide promoted
environmentally benign thiolysis of epoxides
Leave this area blank for abstract info.
Najmedin Azizi,* Mahtab Edrisi

1
Tetrahedron Letters
Biodegradable choline hydroxide promoted environmentally benign thiolysis of
epoxides
Najmedin Azizi Mahtab Edrisi
Chemistry & Chemical Engineering Research Center of Iran, P.O. Box 14335-186, Tehran, Iran
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An environmentally benign and rapid thiolysis of epoxides using a biodegradable, choline-based
task-specific ionic liquid has been developed. The ring opening reaction of aryl and alkyl
epoxides proceeded rapidly and afforded the corresponding β-hydroxysulfides in high yields
with excellent regioselectivity. The protocol has the advantages of easy work-up, short reaction
times, high yields and a biodegradable catalyst.
Available online
2014 Elsevier Ltd. All rights reserved.
Keywords:
Thiols
choline hydroxide
green chemistry
epoxide
task-specific ionic liquids
Task-specific, functionalized ionic liquids with unique
physico-chemical properties have received increased attention
over the last few years.1 The incorporation of acidic or basic
functional groups in the ionic liquid provides extra capacity to
behave not only as a green reaction medium, but also as a
recyclable promoter or catalyst in different organic reactions.2
Despite the valuable properties of traditional task-specific ionic
liquids based on imidazolium and pyridinium salts, they possess
disadvantages such as toxicity, difficult preparation and high
cost.3 Choline hydroxide (ChOH) is a non-toxic and naturally
abundant task-specific ionic liquid which can be used to carry the
hydroxide ion into organic systems (Fig. 1). It is water-soluble
and can be easily prepared from biodegradeable and low cost
starting materials in high purity. Moreover, it is an excellent
phase transfer catalyst in terms of activity and selectivity.4
to the best of our knowledge, there are no report of the thiolysis
of epoxides using choline hydroxide.
In recent years, significant development has taken place in
green chemistry using water and ionic liquids as an
environmentally benign reaction media in place of traditional
organic reaction media.10As a part of our research to develop
green chemistry using deep eutectic solvents as reaction
mediums,11 herein, we report a simple, practical and effective
process for synthesizing β-hydroxysulfides via the choline
hydroxide promoted thiolysis of epoxides. The combination of
using a green phase transfer promoter and solvent-free condition
gives excellent yields and reduces the reaction times, making this
a highly eco-friendly methodology to prepare β-hydroxysulfides.
The thiolysis of 1,2-epoxides under mild and eco-friendly
conditions, is a useful method for the construction of the β-
hydroxysulfide moiety5 which are versatile intermediates in the
synthesis of a variety of biological and pharmaceutically
important products.6 Sulfur-containing organic compounds have
found various applications as antioxidants, chemotherapeutics,
enzyme inhibitors, calcium channel antagonists, and
antimicrobial agents.7 Owing to their significance, the
development of environmentally benign, high yielding, and clean
epoxide thiolysis is still a challenge and has been extensively
investigated.8 The related work has focused on discovering
environmentally friendly solvents, reagents and catalysts for the
clean and fast ring opening of epoxides using thiol.9 Although
Fig. 1. Structure of choline hydroxide
Initially, we investigated the thiolysis of cyclohexene oxide
with thiophenol as a model reaction in the presence of ChOH
(Table 1). The reaction proceeded smoothly at room temperature
in the presence of 50 mol% of ChOH, to give the desired product
3a in quantitative yield after 30 minutes. When the amount of
ChOH was decreased to 30 mol%, the yield of the product 3a
was reduced, and with 100 mol% loading of ChOH there was no
improvement. Furthermore, without any ChOH only 40% yield
was obtained with a much longer reaction time (Table 1, entry 1).
Screening of different amounts of ChOH revealed that 50 mol%
some of these reported procedures are environmentally friendly,
———
 Corresponding author. Tel.: +98-21-44580-775; fax: +98-214-4580-762; e-mail: azizi@ccerci.ac.ir

2
Tetrahedron Letters
of ChOH was the most effective in terms of yields and time.
confirmed by comparison of the 1HNMR spectral data with those
reported in the literature.13
Furthermore, the model reaction was carried out using common
organic hydroxides such as Bu4NOH, Me4NOH, triton B, organic
base (Et3N) and a few commerically avaliable inorganic bases
such as KOH and NaOH in order to substantiate the task-specific
functionalized ionic liquids effect. All of the tested bases gave
lower yields under the optimized reaction conditions (Table 1).
In summary, a convenient, quick and green thiolysis of 1,2-
epoxides with aromatic thiols using choline hydroxide as a
environmentally benign catalyst has been developed. Using a
biodegradable and inexpensive choline hydroxide under solvent
free conditions provide a selective synthesis of β-hydroxysulfides
in good to excellent yields.14,15
Table 1. Optimization of the model reaction
Table 2. Ring opening of cyclohexane oxide with thiols promoted by ChOH.
Entry
Catalyst
(mol%)
Time (min)
Yield (%)a,b
1
2
3
4
5
6
7
8
9
10
11
12
13
none
400
400
30
30
30
30
30
30
30
30
30
30
30
40
72
60
75
80
95
95
65
52
58
68
56
45
Yielda,
b (%)
Time
(min)
ChOH (1)
ChOH (5)
ChOH (10)
ChOH (30)
ChOH (50)
ChOH (100)
Et3N (50)
KOH (50)
NaOH (50)
Bu4NOH (50)
Me4NOH (50)
triton B (50)
Entry
1
ArSH
3a-3g
95
95
88
90
80
76
86
109e
109e
609b
459f
359g
806b
608b
2
3
4
5
6
7
Isolated yield. b Reaction conditions: cyclohexene oxide (1 mmol),
thiophenol (1 mmol), catalyst, r.t..
a
Having established suitable reaction conditions, various
structurally diverese epoxides and arylthiophenols were applied
to the synthesis of various β-hydroxyarylsulfides in order to
investigate the reaction scope. It was observed that sterically,
electronically and functionally diverse thiophenols reacted with
cyclohexane oxide to give the corresponding products in good to
excellent yields (Table 2). The reactions were chemoselective
and epoxide cleavage with reactive functional groups such as -
OH was not observed. Furthermore, the reactions were
stereoselective and trans stereochemistry of the ring products
were confirmed by the coupling constants of the C–H protons
adjacent to the heteroatoms in the 1H NMR spectra.
Next, the synthetic utility of this protocol was demonstrated
by the use of various alkyl- and aryl-epoxides and thiol
substrates. Thiolysis of alkyl- and aryl-epoxides such as phenyl
2,3-epoxypropyl ether, isopropyl-2,3-epoxypropyl ether, 1,2-
epoxy butane, allyl-2,3-epoxypropyl ether and styrene oxide,
with aryl thiols possessing different substituents (4-MeO, 4-Cl, 4-
Br, and 4-Me) on the phenyl ring are shown in Table 3. The
obtained results revealed that reaction of the epoxides and thiols
proceed smoothly and afforded the corresponding β-
hydroxysulfides in good to excellent isolated yield with high
regioselectivity (Table 3).
a
Isolated yields. b Reaction conditions: cyclohexene oxide (1 mmol),
ArSH (1 mmol), ChOH (50 mol%), r.t.
Acknowledgments
Financial support of this work by the Chemistry and Chemical
Engineering Research Center of Iran is gratefully appreciated.
References and notes
The regioselectivity in the reaction of unsymmetrical epoxides
is governed by both steric and electronic effects. Selective
nucleophilic attack of arylthiols occurred exclusively on the less
substituted carbon atom of aliphatic epoxides. Styrene oxide
undergoes regioselective nucleophilic attack at the benzylic
position under electrophilic activation (i.e., Lewis acid catalysed
epoxide ring opening) while under neutral or basic conditions
leads to nucleophilic attack at the less hindered terminal position
via a SN2 mechanism.9a,12 Styrene oxide reacted under standard
reaction conditions with short reaction times and excellent yields.
However, regioselectivity was not observed for this substrate,
and both regio-isomers were formed. Their structures were
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14. Preparation of choline hydroxide: The choline hydroxide based ionic
liquid was prepared according to the literature.4 Choline chloride (10
mmol) and KOH (10 mmol) in methanol (15 mL) were heated at reflux
for 12 h under N2. After cooling to room temperature, the reaction
mixture was filtered to remove solid KCl and the solution was
concentrated under vacuum to remove methanol. The residue was
dissolved in water to prepare 40% by weight of the choline hydroxide
solution which was used without any further purification.
15. General procedure: A test tube, equipped with a magnetic stir bar, was
charged with epoxide (1.0 mmol), thiol (1.0 mmol), and ChOH (50
mol%). The resulting mixture was stirred at room temperature until the
reaction was complete (5-80 min). The reaction mixture was diluted
with ethyl acetate (10 mL) and washed with water (10 mL) to remove
the ChOH. The organic layer was dried over Na2SO4 and evaporated
under vacuum. In some cases, the crude products were purified by flash
column chromatography using silica gel or recrystallization from
ethanol or diethyl ether. All products are known compounds and the
characterization data of these compounds were identical to literature
reports.
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4
Tetrahedron Letters
Table 3. Ring-opening of various epoxides with thiols promoted by ChOH
Entry
1
Product
Yield
(%)a
959b
Entry
9
Product
Yield
(%)a
829b
2
3
4
929b
9013c
929h
10
11
12
889h
786a
806a
5
6
757b
788b
13
14
759e
789i
7
8
869a
15c
16c
9214a
808a
9414c
a
Isolated yield. b Reaction Conditions: epoxide (1 mmol), ArSH (1 mmol), ChOH (50 mol%), r.t. c 1H NMR yield