Solid-Liquid Phase-transfer Catalytic Synthesis of Chiral Glycerol Sulfide Ethers under Microwave Irradiation

Article abstract of DOI:10.1039/a708058a

Epoxypropoxyphenols react with benzenethiols under phase-transfer catalysis and microwave irradiation to give chiral glycerol sulfide ethers, this procedure is simple, rapid and efficient.

Full text of DOI:10.1039/a708058a

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216 J. CHEM. RESEARCH (S), 1998
J. Chem. Research (S),
1998, 216±217$
Solid±Liquid Phase-transfer Catalytic Synthesis of
Chiral Glycerol Sulfide Ethers Under Microwave
Irradiation$
Jing-Xian Wang,* Yumei Zhang, Danfeng Huang and Yulai Hu
Institute of Chemistry, Department of Chemistry, Northwest Normal University,
95 An Ning Road(E.), Lanzhou 730070, China
Epoxypropoxyphenols react with benzenethiols under phase-transfer catalysis and microwave irradiation to give chiral
glycerol sulfide ethers, this procedure is simple, rapid and efficient.
The rapid heating of foodstu€s in microwave ovens is
routinely used by mankind. However, people have
recognized other potential applications for this method of
heating and scientists engaged in a number of disciplines
have applied the rapid heating associated with microwave
technology to a number of useful processes. These include
the preparation of samples for analysis, applications to
waste treatment, polymer technology, drug release/targeting,
ceramics and alkane decomposition processes, hydrolysis of
proteins and peptides inorganic and solid-state synthesis. So
it is organic synthesis which bene®ts signi®cantly from this
technology.1±3 Our work involves the synthesis of chiral
glycerol sul®de ethers in a modi®ed commercial microwave
oven.
conditions. However, they have synthesied only one isomer
and since these compounds can be separated into two kinds
of chiral compounds, they may have some biological
activity, so it is very interesting to investigate these com-
pounds. We have now found that chiral glycerol sul®de
ethers can be obtained from epoxypropoxyphenols and
benzenethiols using microwave irradiation. This method is
simple, rapid and a€ords good yields. It takes only 8 min
for the reaction to ®nish (compared to 5 h for the synthesis
by Iizawa et al.4). The reactions are shown in Scheme 1 and
the results are summarized in Table 1.
Since atomic sulfur is easily polarized, the e€ect of the R1
groups of substituted benzenethiols is important in deter-
mining the yield of the chiral glycerol sul®de ethers. When
the substituted benzenethiol contains an eletron-releasing
group such as Me, the yield of the corresponding glycerol
sul®de ether is high (73%), and when the substituent is an
electron-withdrawing group such as NO2 the yield of the
corresponding glycerol sul®de ether is low.
In the past, Iizawa et al.4 have reported the synthesis of
3-hydroxy-3-(phenylthio)propyl phenyl ether under normal
Using the reaction of PhCH2SH with epoxypropoxy-
phenol as an example, we investigated the e€ect of phase-
transfer catalysts (PTC) on the reaction. When PEG-400 (or
PEG-600) was used as a phase-transfer catalyst, the yield
of the glycerol sul®de ether is high (89.3%) whereas the
yield is only 67.6% without any PTC. The eciency of
several PTCs studied is in the order PEG-4001PEG-600 >
Bu4NBr > Me4NI.
The e€ect of various solvents used in the formation of
chiral glycerol sul®de ethers was studied and DMF was
found to be the best solvent for the reactions. This is
because DMF is a polar solvent and it's boiling point is
high, it can eciently absorb microwave energy, also
sodium aryl thiolates are soluble in DMF. Other solvents
were studied for these reactions and their suitability are in
the order DMF > EtOH > butanol > acetone. Power and
reaction time also in¯uence the yield of the glycerol sul®de
ethers which is greatest at 750 W and 8 min.
Experimental
Infrared spectra were measured as KBr discs (or liquid ®lm) using
an Alpha Centauri FT-IR spectrophotometer, 1H NMR spectra
(80 MHz) were recorded in CDCl3 [or (CD3)2CO] using an FT-80
spectrometer, mass spectra were obtained on a Nippon Shimadzu
QP-1000 GC-MS spectrometer. Microwave irradiations are carried
out in a modi®ed Galanz WP 750B commercial microwave oven at
2450 MHz.
General Procedure.ÐIn a typical experiment, the benzenethiol
(5.4 mmol), sodium hydroxide (0.4 g, 9.6 mmol), PEG-400 (0.1 g)
and DMF (10 ml) were added in a bottle (100 ml), and then re¯uxed
under microwave irradiation with 100% power (750 W). After 1 min
Scheme 1
a
mixture of the epoxypropoxyphenol5,6 (5.8 mmol) and DMF
(2 ml) was added dropwise over a period of 1.5 min and irradiated
continuously for 5.5 min. The solid was ®ltered o€ and the ®ltrate
taken to dryness under reduced pressure. The residue was acidi®ed
with dilute HCl and extracted with diethyl ether and the solution
dried over MgSO4. After ®ltration, the diethyl was evaporated to
yield crude product which was chromatographed on silica gel
*To receive any correspondence.
$This is a Short Paper as de®ned in the Instructions for Authors,
Section 5.0 [see J. Chem. Research (S), 1998, Issue 1]; there is there-
fore no corresponding material in J. Chem. Research (M).

View Article Online
J. CHEM. RESEARCH (S), 1998 217
Table 1 Preparation of chiral glycerol sulfide ethers (5a-o)
Reaction
time/
min
Found (calcd) (%)
1
Yield Molecular
Mp/8C (%) formula
ꢀ
max/cm
(KBr)
MS
(m/z)
Compound
C
H
O
S
dH (CDCl3, Me4Si)
‡
5a
8
Oil
92 C15H16O2S 69.46
6.19
12.04 12.44 3426, 2926, 2.49 (s, 1 H, OH), 3.21
260 (M )
(69.23) (6.15) (12.31) (12.31) 1599, 1244, (m, 2 H, Ha), 4.09 (m,
690
3 H, Hb), 6.81±7.49 (m,
10 H, aromatic)
‡
5b
5c
8
8
Oil
73 C16H18O2S 70.06
(70.07) (6.57) (11.68) (11.68) 1599, 1588,
690, 2871
6.30
12.20 11.44 3426, 2923, 1.26 (s, 1 H, OH), 3.13
274 (M )
(m 2 H, Ha), 4.04 (m,
3 H, Hb), 6.81±7.92
‡
53.2± 90 C17H20O2S 70.82
53.9
6.68
11.39 11.11 3575, 2919, 2.28 (d, 6 H, CH3), 2.72 288 (M )
(70.83) (6.94) (11.11) (11.11) 1610, 1585, (s, 1 H, OH), 3.17 (m, 289 (M ‡ 1)
1243, 631
2 H, Ha), 4.01 (s, 3 H,
Hb), 6.71±7.38, (m, 8 H,
aromatic)
‡
5d
5e
5f
8
8
8
Oil
91 C19H18O2S 73.37
5.72
10.40 10.51 3427, 2926, 2.72 (s, 1 H, OH), 3.28
310 (M )
(73.55) (5.81) (10.32) (10.32) 1590, 1564, (m, 2 H, Hb), 4.04 (s, 3 H,
1244, 690 Ha), 6.77±8.50, (m, 12 H,
aromatic)
3406, 2927, 2.37 (s, 1 H, OH), 3.35
‡
Oil
79 C23H20O2S 76.61
5.61
8.71
9.07
360 (M )
(76.67) (5.56) (8.89) (8.89) 1595, 1580, (m, 2 H, Ha), 4.21 (m,
1241, 665 3 H, Hb), 6.65±8.51, (m,
14 H, aromatic)
121± 88.9 c20H18O4S 67.79
122
5.04
18.08
9.11
3445, 1690, 3.37 (m, 2 H, Ha), 4.41
(67.80) (5.08) (18.08) (9.04) 1596, 1580, (m, 3 H, Hb), 4.95 (s, 2 H,
2930, 1243, CO2H ‡ OH), 6.75±8.81
‡
645
(m, 11 H, aromatic)
354 (M )
‡
5g
5h
8
8
Oil
75 C20H20O2S 74.19
5.99
9.77
10.05 3427, 2023, 2.26 (s, 3 H, CH3), 2.43
324 (M )
(74.07) (6.17) (9.88) (9.88) 1587, 1613, (s, 1 H, OH), 3.26 (m,
1382, 601
2 H, Ha), 3.26 (m, 2 H,
Ha), 6.67±8.49 (, 11 H,
aromatic)
‡
54.5± 89.3 C16H18O2S 69.92
55.2
6.53
11.74 11.81 3394, 2926, 1.63 (s, 1 H, OH), 2.74
274 (M )
(70.07) (6.57) (11.68) (11.68) 1599, 1587, (m, 2 H, Ha), 3.78 (m,
1492, 1244, 2 H, Ha), 4.01 (s, 3 H,
687
Hb), 6.84±7.40 (m, 10 H,
aromatic)
‡
5i
5j
8
8
Oil
67 C19H18O2S 73.25
5.80
10.53 10.40 3422, 2927, 2.56 (s, 1 H, OH), 3.31
310 (M )
(73.55) (5.81) (10.32) (10.32) 1595, 1580, (m, 2 H, Ha), 4.23 (m, 3
1241, 690 H, Hb), 6.70±8.27 (m, 12
H, aromatic)
‡
55±
55.9
70 C17H20O2S 70.96 6.69
(70.83) (6.94) (11.11) (11.11) 1585, 1512, (s, 3 H, CH3), 2.69 (m,
11.14 11.21 2920, 1613, 1.60 (s, 1 H, OH), 2.29
288 (M )
1379, 1242, 2 H, Ha), 3.76 (s, 2 H,
700
Hb), 3.98 (s, 3 H, Hb),
6.73±7.31 (m, 9 H,
aromatic)
‡
5k
5l
8
8
8
8
52±
52.6
97 C16H18O2S 70.19
(70.07) (6.57) (11.68) (11.68) 1582, 1611, (s, 1 H, OH), 3.20 (m,
1608, 1386, 2 H, Ha), 6.71±7.41 (m,
1244, 688 9 H, aromatic)
6.56
11.43 11.82 3574, 2917, 2.28 (s, 3 H, CH3), 2.48
264 (M )
‡
Oil
82.4 C20H20O2S 74.12
6.08
10.11
9.69
3419, 2873, 2.28 (s, 3 H, CH3), 3.25
324 (M )
(74.07) (6.17) (9.88) (9.88) 2923, 1596, (m, 2 H, Ha), 4.21 (s, 3 H,
1580, 572 Hb), 6.67±8.29 (m, 11 H,
aromatic)
‡
5m
5n
111±
111.7
94 C16H16O4S 62.92
4.98
21.53 10.57 3191, 2923, 3.30 (m, 2 H, Ha), 4.26
304 (M )
(63.16) (5.26) (21.05) (10.53) 1690, 1587, (m, 3 H, Hb), 5.75 (s, 2
1563, 1496, H, CO2H ‡ OH), 6.85±
685 8.11 (m, 9 H, aromatic)
10.07 3500, 2926, 2.48 (s, 1 H, OH), 2.81
‡
62±
62.5
80 C20H20O2S 74.46
5.96
9.51
324 (M )
(74.07) (6.17) (9.88) (9.88) 1620, 1595, (m, 2 H, Ha), 3.79 (s, 2 H,
1580, 1243, Ha), 4.18 (m, 3 H, Hb),
700
6.74±8.22 (m, 12 H,
aromatic)
3503, 2925, 2.28 (s, 3 H, CH3), 3.28
‡
5o
8
113± 66.7 C17H18O4S 64.21
114
5.57
20.41
9.81
318 (M )
(64.15) (5.66) (20.13) (10.06) 1674, 1588, (m, 2 H, Ha), 4.10 (m,
1563, 1514, 3 H, Hb), 5.45 (s, 2 H,
1256, 690 CO2H ‡ OH), 6.75±8.14
(m, 8 H, aromatic)
[eluent: light petroleum (bp 60±90 8C)±ethyl acetate (16:1 v/v)] or
crystallized.
2 C. R. Strauss and R. W. Trainor, Aust. J. Chem., 1995, 48, 1665.
3 K. D. Raner, C. R. Strauss, R. W. Trainor and J. S. Thorn,
J. Org. Chem., 1995, 60, 2456.
4 T. Iizawa, A. Goto and T. Nishikubo, Bull. Chem. Soc. Jpn.,
1989, 62, 597.
5 Jin-Xian Wang, Manli Zhang and Yulai Hu (Submitted for publi-
cation).
6 S. S. Jovanovic, M. M. Misic-Vukovic, D. D. Djokovic and D. S.
Bajic, J. Mol. Catal., 1992, 73, 9.
Received, 10th November 1997; Accepted, 12th January 1998
Paper E/7/08058A
References
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