Cyanuric chloride: An efficient catalyst for ring opening of epoxides with thiols under solvent-free conditions

Article abstract of DOI:10.1071/CH07079

2,4,6-Trichloro-1,3,5-triazine-catalyzed convenient and efficient ring opening of epoxides with thiols under solvent-free conditions is described. Short reaction time, mild reaction conditions, inexpensive and readily available catalyst, and excellent yie

Full text of DOI:10.1071/CH07079

Short Communication
CSIRO PUBLISHING
www.publish.csiro.au/journals/ajc
Aust. J. Chem. 2008, 61, 231–234
Cyanuric Chloride: an Efficient Catalyst for Ring Opening
of Epoxides with Thiols Under Solvent-Free Conditions
Babasaheb P. Bandgar,A,B Neeta S. Joshi,A Vinod T. Kamble,A
and Sanjay S. SawantA
AOrganic Chemistry Research Laboratory, School of Chemical Sciences, Swami Ramanand Teerth
Marathwada University, Nanded 431606, Maharashtra, India.
BCorresponding author. Email: bandgar_bp@yahoo.com
2,4,6-Trichloro-1,3,5-triazine-catalyzed convenient and efficient ring opening of epoxides with thiols under solvent-free
conditions is described. Short reaction time, mild reaction conditions, inexpensive and readily available catalyst, and
excellent yields of products are attractive features of this methodology.
Manuscript received: 15 March 2007.
Final version: 6 February 2008.
Epoxides are well-known carbon electrophiles capable of react-
ing with various nucleophiles, and their ability to undergo
regioselective ring-opening reactions contributes largely to their
synthetic value.[1,2] The ring opening of 1,2-epoxides with thi-
ols to yield β-hydroxy thioethers is of considerable importance
in the field of natural products, particularly for the synthesis of
leukotrienes, such as LTC4 and LTD4.[3] The most common pro-
tocol to achieve the ring-opening process by thiol is the direct
displacement reaction of 1,2-epoxides with thiols in the pres-
ence of a base (NaOH or Et3N) in a protic solvent (MeOH).[3,4]
Several methods have been developed using Lewis acids such
as boron trifluoride etherate,[5] lanthanide chloride,[6] lithium
perchlorate,[7] cobalt(iii) chloride,[8] and neutral alumina[9] to
perform these epoxide opening reactions.
with thiophenol under various conditions (Table 1). The reaction
is slow in the absence of catalyst (Table 1, entry 1). However,
inferior results are obtained with solvents such as CH2Cl2, THF,
CH3CN, and CHCl3 (Table 1, entries 3–6). Next, we optimized
the quantity of catalyst at room temperature under solvent-
free conditions for this reaction (Table 1, entries 7–11). It was
observed that the use of only 2 mol-% is sufficient to push the
reaction forward. Larger amounts of catalyst did not improve the
results (Table 1, entries 10, 11).
Table 1. Cyanuric chloride-catalyzed reaction of styrene oxide with
thiophenol under various conditions
In recent years, there has been considerable growth in interest
in the use of 2,4,6-trichloro-1,3,5-triazine or its derivatives in
organic synthesis.[10] Recent results from our laboratory show
that simple and readily available 2,4,6-trichloro-1,3,5-triazine
(cyanuric chloride) can assist some important reactions[10n–p]
such as monoacylated piperazines, 2-oxazolines, and synthesis
of acyl azides. These results prompted us to explore the catalytic
activity of cyanuric chloride for the ring opening of epoxide by
thiol. In the present Communication, we report the ring opening
of epoxide by thiol using catalytic amounts of cyanuric chloride
(2 mol-%) under solvent-free conditions (Scheme 1).
Entry
Solvent
Catalyst [mol-%]
Time [min]
Yield [%]
1
2
3
4
5
6
7
8
Neat
CH2Cl2
THF
CH3CN
CHCl3
Neat
Neat
Neat
Neat
Neat
–
2
2
2
2
0.5
1
1.5
2
2.5
3
1200
45
60
45
45
60
60
60
15
15
15
15
65
70
60
65
50
65
85
97
97
97
9
10
11
Initially, a systematic study was carried out for the catalytic
evaluation of cyanuric chloride for the reaction of styrene oxide
Neat
Cl
N
N
OH
SR
N
O
Cl,
(2 mol-%)
OH
SR
Cl
R
SH
ϩ
Ph
ϩ Ph
Ph
Neat, r.t.
1
2
3
4
Scheme 1.
© CSIRO 2008
10.1071/CH07079
0004-9425/08/030231

232
B. P. Bandgar et al.
Table 2. Cyanuric chloride-catalyzed synthesis of β-hydroxy thioethers
Yields refer to the pure isolated products. All reactions confirmed by IR, 1H NMR, and mass spectroscopy
Entry
Epoxides
Thiols
Products
Time [min]
Yield (%)
(1)
(2)
(3,4)
3:4
SPh
O
O
a
PhSH
15
25
97:3
95:4
OH
Ph
Ph
Ph
Ph
Ph
S
CH3
SH
H3C
b
OH
O
O
S
S
Cl
SH
Cl
c
20
94:3
Ph
Ph
OH
CH2Ph
OH
d
e
f
PhCH2SH
25
25
15
92:4
3:92
4:92
Ph
O
OH
SPh
PhSH
H3C
H3C
H3C
O
OH
SH
H3C
CH3
S
H3C
Cl
OH
O
g
h
PhSH
20
25
5:93
5:94
SPh
ClCH2
ClCH2
OH
O
SH
H3C
Cl
CH3
S
OH
O
i
PhSH
20
3:94
SPh
OH
H3C
SH
O
j
5
3:94
3:94
S
CH3
O
OH
k
PhSH
20
PhO
SPh
PhO
The reaction of styrene oxide (1 mmol) and thiophenol
(1 mmol) in the presence of a catalytic amount of cyanuric
chloride (2 mol-%) at room temperature afforded the β-hydroxy
arylsulfide 3a in 97% yield with high regioselectivity; a trace
amount of 4a was also obtained (Scheme 1).
Results are summarized in Table 2. Aryl oxiranes underwent
cleavage by a variety of thiols with preferential attack at the
benzylic position (Table 2, entries a–d). Similarly, reaction of
2,3-epoxypropyl phenyl ether with thiol resulted in the formation
of the corresponding β-hydroxy sulfide in good yield (Table 2,
entry k). Also, alkyl oxiranes underwent cleavage by a variety of
thiols in a regioselective manner with preferential attack at the
terminal position (Table 2, entries e–h).
Further, cyclohexene oxides reacted smoothly with thiols to
afford the corresponding β-hydroxy aryl sulfides in which a trans
stereospecificity was observed in good yields (Table 2, entries
i–j).
The trans stereochemistry of the ring product was found from
the coupling constant of the ring protons at δ 2.78 (ddd, J 4.4,
1
9.7, 11.6 Hz, 1H) for –SCH in the H NMR spectrum and at
δ 3.31 (ddd, J 4.4, 9.7, 9.8 Hz) for –OCH.
When comparing the results obtained with a representative
reaction of styrene oxide with thiophenol, the present method is
convincingly superior to the reported methods with respect to the
amount of catalyst loading, reaction time, and regioselectivity
(Table 3).

Cyanuric Chloride: an Efficient Catalyst
233
Table 3. Comparative study of cyanuric chloride-catalyzed thiolysis of styrene epoxides with literature-reported methods
TBAF, tetrabutyl ammonium fluoride
Entry
Catalyst
Catalyst [mol-%]
Solvent
Time [h]
Yield [%]
Ratio of 3:4
Ref.
1
2
3
4
5
6
p-TsOH
Bun3P
ZnCl2
TBAF
Ph3B
5
5
10
5
5
2
–
–
H2O
–
CH2Cl2
–
48
20
0.33
2
2
0.25
73
95
95
64
84
95:5
11
11
12
13
14
–
37:63
83:17
34:64
84:0
Cyanuric chloride
100
97:3
Cl
Cl
N
N
Cl
Cl
N
N
Cl
ClϪ
N
N
Cl
O
N
SPh
ϩ
O
N
N
Cl
SPh
N
Cl
O
N
R
OH
ϩ
HO
R
R
Cl
N
R
HOH
RЈSH
Cl
Cl
N
Cl
N
N
N
N
N
N
N
ϩ
O
OH
N
Cl
O
Cl
SRЈ
HO
ϩ
R
Cl
SRЈ
R
R
RЈSH
HOH
Scheme 2.
In conclusion, the results in the present paper describe a sim-
ple, convenient, and efficient method for the regioselective ring
opening of epoxides with thiols using catalytic amounts of cya-
nuric chloride, the proposed mechanism of which is described
below (Scheme 2).
1H). m/z 230 [M+]. Calc. for C14H14OS 230.23; C 73.0, H 6.1,
S 13.9. Found: C 73.0, H 6.1, S 14.0%.
2-(4-Methylphenylthio)-2-phenylethanol 3b
Yellow oil. νmax/cm−1 (neat) 3340, 1632, 1505, 1245, 1069, 695.
δH (300 MHz, CDCl3) 7.50 (m, 5H), 7.35 (d, 2H, J 8), 7.12 (d,
2H, J 8), 4.60 (t, 1H, J 6), 3.71 (d, 2H, J 6), 2.59 (s, 3H), 2.31
(s, 1H). m/z 244 [M+]. Calc. for C15H16OS 244.35; C 73.7,
H 6.6, S 13.12. Found: C 73.7, H 6.6, S 13.1%.
Experimental
1H NMR spectra were recorded in CDCl3 at 300 MHz using
TMS as internal standard. IR spectra were recorded neat for
liquid samples and using KBr pellets for solids. Column chro-
matography was performed using silica gel (100–200 mesh).
Chemical shifts are given in ppm with respect to internal TMS,
and J values are quoted in Hz.
2-(4-Chlorophenylthio)-2-phenylethanol 3c
Yellow oil. νmax/cm−1 (neat) 3425, 1655, 1221, 1060, 815. δH
(300 MHz, CDCl3) 7.45 (m, 5H), 6.84 (d, 2H, J 8), 6.80 (d, 2H,
J 8), 3.70 (m, 1H), 3.40 (m, 2H), 2.61 (br s, 1H). m/z 264 [M+].
Calc. for C14H13ClOS 264.76; C 63.5, H 4.9, Cl 13.4, S 12.1.
Found: C 63.5, H 4.9, Cl 13.3, S 12.1%.
General Experimental
A mixture of epoxide (5 mmol), thiol (5 mmol), and cyanuric
chloride (2 mol-%) was stirred at ambient temperature for an
appropriate time (Table 2). After completion of reaction as
indicated by TLC, the reaction mixture was diluted with H2O
(2 × 10 mL) and extracted with diethyl ether (2 × 15 mL). The
combined organic layer was dried over anhydrous Na2SO4,
concentrated under vacuum, and purified by column chro-
matography on silica gel (Merck 60–120 mesh, 9 : 1 petroleum
spirits/ethyl acetate) to afford pure product.
2-Benzylthio-2-phenylethanol 3d
Yellow oil. νmax/cm−1 (neat) 3365, 1629, 1530, 1258, 1055, 725.
δH (300 MHz, CDCl3) 7.38 (d, 2H, J 8.0), 7.20 (d, 2H, J 8.0),
4.70 (t, 1H, J 7.9), 3.62 (d, 2H, J 6.5), 2.65 (br s, 1H). m/z 264
[M+]. Calc. for C15H16OS 244.35; C 73.7, H 6.6, S 13.1. Found:
C 73.7, H 6.5, S 13.3%.
2-Phenylthio-2-phenylethanol 3a
2-Phenylthiopropan-2-ol 4e
Yellow oil. νmax/cm−1 (neat) 3432, 2928, 2855, 1712, 1621,
1445, 1402, 1213, 1122, 1018, 769. δH (300 MHz, CDCl3):7.17–
7.38 (m, 10H), 4.26 (t, 1H, J 7.8), 3.83 (d, 2H, J 8.0), 2.07 (br s,
Yellow oil. νmax/cm−1 (neat) 3727, 2995, 1638, 1504, 1374,
1243, 1408, 757. δH (300 MHz, CDCl3) 7.38 (m, 5H), 3.58 (m,
1H), 2.79 (d, 2H, J 7.3), 2.58 (br s, 1H), 1.22 (d, 3H, J 7.2).

234
B. P. Bandgar et al.
2-(4-Methylphenylthio)-1-methylethanol 4f
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Oil. νmax/cm−1 (neat) 3452, 1622, 1530, 1041, 820. δH
(300 MHz, CDCl3) 7.32 (d, 2H, J 8.4), 7.12 (d, 2H, J 8.4), 3.8
(m, 1H), 2.64 (dd, 1H, J 3.8, 13.8), 2.59 (s, 1H), 2.41 (dd, 1H, J
8.5, 13.6), 1.88 (d, 3H, J 7). m/z 182 [M+]. Calc. for C10H14OS
182.279; C 65. 9, H 7.7, S 17.6. Found: C 65.9, H 7.7, S 17.5%.
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1-Phenylthio-3-chloropropan-2-ol 4g
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Yellow oil. νmax/cm−1 (neat) 3366, 2964, 2916, 1742, 1525,
1231, 1048, 769. δH (300 MHz, CDCl3) 7.15–7.35 (m, 5H), 4.05
(m, 1H), 3.68 (d, 2H, J 9), 3.08 (d, 2H, J 6.6), 2.26 (br s, 1H). m/z
202 [M+]. Calc. for C9H11OClS 202.69; C 53.3, H 5.5, Cl 17.5,
S 15.8. Found: C 53.3, H 5.4, Cl 17.5, S 15.8%.
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2-(4-Methylphenylthio)-1-chloropropan-2-ol 4h
Colourless oil. νmax/cm−1 (neat) 3415, 1629, 1547, 1251, 1062,
735. δH (300 MHz, CDCl3) 7.35 (d, 2H, J 8.4), 7.22 (d, 2H, J
8.4), 3.90 (m, 1H), 3.80 (s, 3H), 2.70 (d, 2H, J 6), 2.60 (d, 2H,
J 6.2), 2.31 (br s, 1H). m/z 216 [M+]. Calc. for C10H13ClOS
216.72; C 55.4, H 6.0, Cl 16.4, S 14.8. Found: C 55.4, H 6.0,
Cl 16.3, S 14.8%.
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2-Phenylthiocyclohexan-1-ol 4i
Oil. νmax/cm−1 (neat): 3345, 1622, 1510, 1244, 1053, 710. δH
(300 MHz, CDCl3) 7.45 (m, 2H), 7.25 (m, 3H), 3.31 (ddd, 1H, J
4.5, 9.8, 9.8, OCH), 2.76 (ddd, 1H, J 4.5, 9.8, 11.5, SCH), 2.71
(br s, 1H), 2.20 (m, 2H), 1.65 (m, 2H), 1.25 (m, 4H). m/z 208
[M+]. Calc. for C12H16OS 208.31; C 69.2, H 7.7, S 15.4. Found:
C 69.1, H 7.7, S 15.4%.
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2-(4-Methylphenylthio)cyclohexan-1-ol 4j
Oil. νmax/cm−1 (neat) 3365, 2945, 1642, 1535, 1251, 1061, 735.
δH (300 MHz, CDCl3) 7.35 (m, 4H), 3.30 (ddd, 1H, J 4.6, 9.10,
11.5), 2.81 (ddd, 1H, J 4.6, 10.0, 12.2), 2.50 (m, 2H), 2.34 (s,
3H), 2.11 (s, 1H), 1.60 (m, 2H), 1.10 (m, 4H). m/z 222 [M+].
Calc. for C13H18OS 222.34; C 70.2, H 8.2, S 14.4. Found: C 70.2,
H 8.1, S 14.4%.
2-Phenoxy-1-phenylthiopropan-2-ol 4k
Oil. νmax/cm−1 (neat) 3420, 1620, 1517, 1245, 1058, 721. δH
(300 MHz, CDCl3) 7.40 (m, 10H), 4.20 (m, 1H), 3.79 (d, 2H, J
6.9), 3.12 (d, 2H, J 6.7), 2.30 (br s, 1H). m/z 260 [M+]. Calc.
for C15H16O2S 260.34; C 69.2, H 6.2, S 12.3. Found: C 6.2,
H 6.2, S 12.3%.
Acknowledgement
We thank Council of Scientific and Industrial Research, New Delhi, for
financial assistance.
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