Synthesis of β-dihydroxysulfides by cleavage of epoxides using quaternized amino-functionalized cross-linked polyacrylamide as a new polymeric phase transfer catalyst

Article abstract of DOI:10.1080/104265090902651

Poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium halide resin was developed as a new solid-liquid phase transfer catalyst. This quaternized polyacrylamide catalyzed regioselective ring opening of epoxide by Na ₂S to obtain bis[β-hydroxyalkyl]

Full text of DOI:10.1080/104265090902651

Phosphorus, Sulfur, and Silicon, 180:1929–1936, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090902651
Synthesis of β-Dihydroxysulfides by Cleavage
of Epoxides Using Quaternized Amino-Functionalized
Cross-Linked Polyacrylamide as a New Polymeric Phase
Transfer Catalyst
H. Mahdavi
Chemistry Department, Tehran University, Tehran, Iran
B. Tamami
Chemistry Department, Shiraz University, Shiraz, Iran
Poly[N-(2-aminoethyl)acrylamido]trimethyl ammonium halide resin was developed
as a new solid-liquid phase transfer catalyst. This quaternized polyacrylamide
catalyzed regioselective ring opening of epoxide by Na S to obtain bis[β-hydroxy-
2
alkyl]sulfide in high yield under mild conditions.
Keywords β-Dihydroxysulfides; epoxides; phase transfer catalyst; polyacrylamide
INTRODUCTION
Phase Transfer Catalysis (PTC) is now established as a versatile and
important synthetic technique in organic chemistry. Many reviews on
synthetic methods using PTC have been written.1 One of the major
concerns in using PTC in soluble form is its separation from the reaction
mixture. For efficient use of the catalyst and to meet product purity
requirements, synthesis techniques using PTCs involve an additional
separation step for catalyst isolation and product purification. Polymer-
supported phase transfer catalysts,2 also known as triphase catalysts,
provide an attractive means of recycling the catalyst after the reaction.
The 1,2-epoxide functionality is largely present in nature, is biologi-
cally important, and is a powerful building block in organic synthesis.3
Recently, Sharpless,4 following the chemical lead of mother nature, pro-
posed the term “click chemistry,” the synthetic approach that gener-
ates substances “by joining small units together with heteroatom links
Received September 7, 2004; accepted October 5, 2004.
We are thankful to Professor N. Iranpoor for his valuable comments and suggestions.
Address correspondence to H. Mahdavi, Chemistry Department, Tehran University,
Tehran, Iran. E-mail: hmahdavi@khayam.ut.ac.ir
1929

1930
H. Mahdavi and B. Tamami
(C-X-C)” and defined the criteria that a process must meet to be useful
in this context. A “click reaction” that uses this strategy is the nucle-
ophilic ring-opening of 1,2-epoxides.
Generally, β-hydroxysulfides are prepared by a ring-opening reac-
tion of epoxides with thiols.5 The most common protocol to achieve the
ring-opening process by thiols is by the direct displacement reaction of
epoxides with thiols in the presence of a base (NaOH or Et3N) in a protic
solvent (i-PrOH or MeOH).5,6 Similar results are obtained, for example,
when the oxiranes opening reactions with thiols are performed in the
presence of lanthanide trichloride7,8 and metal salts such as LiClO4,
KClO4, and Mg(ClO4)2.9 On the other hand, as far as we know, there
is only one report in the literature on the preparation of symmetrical
β-dihydroxysulfide from the reaction of sulfur nucleophile with epox-
ide rings in the presence of triphenylsilanethiol/CsCO3 (as a solid H2S
equivalent) (Scheme 1).10
SCHEME 1
Recently, we have reported the use of a quaternized amino–
functionalized cross-linked polyacrylamide as an efficient poly-
meric phase-transfer catalyst in the synthesis of halohydrins,11
azidohydrins,12 thiocyanohydrins,13 chemoselective reduction of alde-
hydes and ketones by sodium borohydride,14 and also synthesis of
nitroalcohols.15 This report describes the results that successfully led
to the development of an efficient and simple method for the trans-
formation of epoxides to β-hydroxysulfides using quaternized amino–
functionalized cross-linked polyacrylamide as an efficient heteroge-
neous polymeric PTC in presence of no other catalyst.
RESULT AND DISCUSSION
Polyacrylamide cross-linked with divinylbenzene (2%) was prepared
by free radical solution polymerization of the monomer mixture
in ethanol by using benzoyl peroxide as an initiator. Poly[N-(2-
aminoethyl)acrylamide] was obtained by the transamidation reaction
of cross-linked polyacrylamide with excess ethylene-diamine. Poly[N-
(2-aminoethyl)acrylamido]trimethylammonium chloride was prepared
by the reaction of poly[N-(2-aminoethyl)acrylamide] with an excess of

Synthesis of β-Dihydroxysulfides
1931
methyl iodide in DMF at room temperature and subsequent exchange
of the iodide anion with chloride.11
In view of our results in previous works, and to develop the synthetic
utility of poly[N-(2-aminoethyl)acrylamido]trimethylammonium chlo-
ride, as a phase transfer catalyst the reaction of epoxides with Na2S to
obtain bis[β-hydroxy-alkyl]sulfide under phase-transfer condition was
studied (Scheme 2).
SCHEME 2
To determine the optimum conditions, the conversion of styrene
oxide to the corresponding β-dihydroxysulfide was investigated. The
optimum molar ratio of the polymeric catalyst to epoxide was found
to be 0.25:1 (Table I). The effects of solvents were also investigated
by carrying out the reactions in wet tetrahydroforan, chloroform,
dichloromethane, ethyl acetate, acetonitrile, and water (Table II). The
best solvent was found to be acetonitrile.
The reactions of different epoxides carrying electron-donating or
withdrawing groups with Na2S were performed in acetonitrile at room
temperature in the presence of 0.25 molar equivalents of the polymeric
phase-transfer catalyst. The corresponding β-dihydroxysulfides were
obtained in high yields (Table III).
Except for the reactions of styrene oxide (Table 3, entry 1; Scheme 3)
and 1,2-hexene oxide (Table 3, entry 6) which produce a small percent-
age of both regioisomers, the reactions of other epoxides were found to be
highly regioselective and only one isomer was obtained (e.g., Scheme 4).
SCHEME 3

1932
H. Mahdavi and B. Tamami
SCHEME 4
Also in the case of cyclic epoxides (Table 3, entries 7-8), trans-
products were obtained (e.g. Scheme 5).
SCHEME 5
The observed regio- and stereochemistry clearly indicate that the
reaction proceeds through an SN2 type mechanism, where the nucle-
ophilic attack by the sulfide (S2−) ion at the less-substituted carbon
atom of the epoxide ring, a fact which is reasonably well established.16
Table IV shows a comparison between our results and those reported
by Gareau.10 As seen, when epoxides were allowed to react in the pres-
ence of our catalyst, the yields and regioselectivity were higher than
those reported by the other methods.
As shown in our previous articles, poly[N-(2-aminoethyl)acryla-
mido]trimethylammonium chloride resin in this transformation pre-
sumably acts both as a catalyst for nucleophilic ring opening reactions
as well as being a phase-transfer agent.
In conclusion, poly[N-(2-aminoethyl)acrylamido]trimethyl ammo-
nium chloride resin has proven to be a highly efficient polymeric
TABLE I The Effect of the Molar Ratio of the
Polymeric PTC on the Reaction of Styrene Oxide
with Na2S in Acetonitrile
Entry
Molar ratio of PTC
Time (h)
Conversion %
1
2
3
4
5
6
0.05
0.1
0.15
0.2
0.25
0.25
12
5
3.5
1.45
1
100
100
100
100
100
100
1

Synthesis of β-Dihydroxysulfides
1933
TABLE II The Effect of the Solvent on the
Reaction of Styrene Oxide with Na2S Using the
Polymeric PTCa
Entry
Solvent
Time (h)
Conversion %b
1
2
3
4
5
6
THF
CHCl3
CH2Cl2
CH3COOC2H5
H2O
8
8
8
8
8
1
6
0
12
27
43
100
CH3CN
aThe molar ratio of the polymeric catalyst to styrene
oxide 0.25:1.
bBy GC.
phase-transfer catalyst for the regioselective ring opening of epoxides to
β-dihydroxysulfides by the S2− ion. The resin has the inherent advan-
tages of being a solid phase-transfer catalyst, including operational sim-
plicity, filterability, regenerability, and reuse. In particular, the workup
of the reaction mixture was very easy and the pure products could be
isolated without further purification.
EXPERIMENTAL
(A) Preparation of Poly[N-(2-aminoethyl)acrylamido]trimethyl
Ammonium Iodide
The resin was prepared as described in the our previous papers.16−19
(B) Preparation of bis[β-hydroxy-alkyl]sulfide (General)
To
a
mixture of epoxide (1.0 mmol) and sodium sulfide
(0.85 g, 10 mmol) in CH3CN (10 mL) was added to poly[N-(2-
aminoethyl)acrylamido]trimethylammonium chloride (0.1 g, ∼0.3
mmol Cl−). The suspension was stirred at room temperature for
the lengths of time shown in Table 3. Progress of each reaction was
monitored by TLC, using CCl4-Et2O (5:1) as an eluent and GC. Polymer
and salt were removed by filtration. The organic solvent was dried with
anhydrous Na2SO4. The corresponding pure product was obtained by
evaporation of the solvent. The characterization of the product was
performed by 1H, 13C NMR, and IR spectroscopy.

1934
H. Mahdavi and B. Tamami
TABLE III Reaction of Epoxides with Na2S in the Presence of the 0.2
Molar Equivalent of Poly[N-(2-aminoethyl)acrylamido]trimethyl
Ammonium Chloride Resin as PTCa
Entry
1
Epoxide
Solvent
CH3CN
Time (h)
1
Productb
Yield%c
90(88, 12)
2
3
CH3CN
CH3CN
1.1
1
91
92
4
5
CH3CN
CH3CN
1
1
93
88 (85, 15)
6
7
CH3CN
CH3CN
1
1
93
77
aAll of the reactions were carried out at room temperature.
bProducts were identified by comparison of their IR and NMR spectra and/or
physical data with those reported in the literature.10
cYield refers to the isolated product.

Synthesis of β-Dihydroxysulfides
1935
TABLE IV Reaction of Epoxides with Sulfide Reagents in the
Presence of the Representative Catalysts
a
Reaction
Time
(h)
%
Entry Epoxide Catalyst condition
Product(s)
Yield
1
3
PhSiSH/
CSCO3
MeOH
Reflux
1
1
64(50, 50)
PhSiSH/
CSCO3
MeOH
Reflux
59
90(88, 12)
93
4
6
Na2S/QPA CH3CN/r · t
Na2S/QPA CH3CN/r · t
1
1
QPA: Poly[N-(2-aminoethyl)acrylamido]trimethylammonium chloride.
2. Conversion of Cyclohexene Oxide to
Bis[β-Hydrocyclohexyl]sulfide under PTC: A Typical Procedure
To a mixture of cyclohexene oxide (0.098 g, 1.0 mmol) and Na2S
(0.85 g, 10 mmol) in acetonitrile (20 mL) was added to poly[N-
(2-aminoethyl)acrylamido]trimethylammonium chloride (0.1 ng). The
mixture was stirred at room temperature for 1 h. The polymer
and salt were removed by filtration. The organic solvent was dried
with anhydrous Na2SO4 and evaporated. The product was bis[β-
hydroxycyclohexyl]sulfide in 90% yield. The corresponding data related
to product are shown below:
1
IR (neat) ν 3550, 2930, 2853, 1450, 1207, 1275; H NMR δ 1.2 (m.,
4H, CH2), 1.6 (m., 2H, CH2), 2.0 (m., 2H, CH2), 2.6 (dd , 1H, CHS ),
3.6 (m , 1H, CHOH); 13C NMR δ 25.4, 26.3, 37.9, 38.44, 40.15.

1936
H. Mahdavi and B. Tamami
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