Remarkably selective Ag+ extraction and transport by thiolariat ethers

Article abstract of DOI:10.1021/jo9517611

Synthesis and metal binding properties of thiolariat ethers, where a sulfide side chain is introduced into a framework of a crown ether, have been performed. Remarkably high Ag⁺ selectivity among heavy metal ions was observed in solvent extraction and transport across a liquid membrane using thiolariat ethers with a 15-crown-5 ring as carriers. Thiolariat ethers with a 12-crown-4 or a 18-crown-6 do not exhibit such a high Ag⁺ selectivity. The former binds metal ions weakly, and the latter recognizes Pb²⁺ as well as Ag⁺. The corresponding oxygen analogs, i.e. lariat ethers, do not show Ag⁺ selectivity. The Ag⁺ binding strength of the sulfoxide and sulfone analogs is much lower than that of thiolariat ethers. Thiolariat ethers with a benzocrown framework containing a sulfide chain at the 4 position of the benzene nucleus showed very low affinity to Ag⁺. Extractability and transport ability using various thiolariat ether derivatives strongly suggested that this high Ag⁺ selectivity is a result of the synergistic coordination of the ring oxygen and the sulfur atom of the thiolariat ether. NMR chemical shifts of protons and carbons in the proximity of the sulfur atom of the thiolariat ether were changed significantly in accordance with the synergistic coordination described above. 1:1 Complexation between a thiolariat ether and Ag⁺ were supported by a Job plot using the chemical shift of the methylene protons adjacent to the sulfur atom.

Full text of DOI:10.1021/jo9517611

4342
J . Org. Chem. 1996, 61, 4342-4350
Rem a r k a bly Selective Ag+ Extr a ction a n d Tr a n sp or t by Th iola r ia t
Eth er s
Tatsuya Nabeshima,*,† Naoko Tsukada,‡ Katsunori Nishijima,‡ Hideaki Ohshiro,‡ and
Yumihiko Yano‡
Department of Chemistry, University of Tsukuba, Tsukuba, Ibaraki 305, J apan and Department of
Chemistry, Gunma University, Kiryu, Gunma 376, J apan
Received September 26, 1995X
Synthesis and metal binding properties of thiolariat ethers, where a sulfide side chain is introduced
into a framework of a crown ether, have been performed. Remarkably high Ag+ selectivity among
heavy metal ions was observed in solvent extraction and transport across a liquid membrane using
thiolariat ethers with a 15-crown-5 ring as carriers. Thiolariat ethers with a 12-crown-4 or a 18-
crown-6 do not exhibit such a high Ag+ selectivity. The former binds metal ions weakly, and the
latter recognizes Pb2+ as well as Ag+. The corresponding oxygen analogs, i.e. lariat ethers, do not
show Ag+ selectivity. The Ag+ binding strength of the sulfoxide and sulfone analogs is much lower
than that of thiolariat ethers. Thiolariat ethers with a benzocrown framework containing a sulfide
chain at the 4 position of the benzene nucleus showed very low affinity to Ag+. Extractability and
transport ability using various thiolariat ether derivatives strongly suggested that this high Ag+
selectivity is a result of the synergistic coordination of the ring oxygen and the sulfur atom of the
thiolariat ether. NMR chemical shifts of protons and carbons in the proximity of the sulfur atom
of the thiolariat ether were changed significantly in accordance with the synergistic coordination
described above. 1:1 Complexation between a thiolariat ether and Ag+ were supported by a J ob
plot using the chemical shift of the methylene protons adjacent to the sulfur atom.
The binding affinity of crown ethers is easily modulated
introducing side chains.18-20 Consequently, various mac-
rocyclic hosts with diverse affinity toward metal ions and
other functions should be readily synthesized by changing
the combination of the atoms forming the ring framework
and the side chain.21-24
Strong Ag+ recognition is important for 111Ag-based
radioimmunotherapy25-27 and probably useful for photo-
graphic technology and recovery of Ag+ from waste water.
Several Ag+ binders have been reported, e.g. crown ethers
containing sulfur atom(s) in the cyclic structure,28-32
double-armed14,15 or multiarmed macrocycles,25,26 and
recently the calixspherands.27 Regulation of Ag+ binding
by introducing a polyether side chain into the crown ring,
because in the modified crown ethers, i.e., lariat ethers,
synergistic coordination of the ring oxygen and the
additional oxygen atoms of the side chain to metal ions
can take place.1-4 Hence, this simple modification of the
metal binding site results in effective changes of ther-
modynamic as well as kinetic binding behavior of crown
ethers.5,6 A side chain containing soft ligating atom(s)
or a functional group can also be incorporated into the
cyclic frameworks.7-13 Preparation of crown ethers with
several side chains can be performed, and drastic im-
provement of binding selectivity toward metal ions has
been achieved.7,14-17 Crown ethers with catalytic activity
for amide bond formation were also synthesized by
(15) Tsukube, H.; Yamashita, K.; Iwachido, T.; Zenki, M. J . Org.
Chem. 1991, 56, 268-272.
(16) Tsukube, H.; Uenishi, J .; Higaki, H.; Kikkawa, K.; Tanaka, T.;
Wakabayashi, S.; Oae, S. J . Org. Chem. 1993, 58, 4389-4397.
(17) Gatto, V. J .; Arnold, K. A.; Viscariello, A. M.; Miller, S. R.;
Morgan, C. R.; Gokel, G. W. J . Org. Chem. 1986, 51, 5373-5384.
(18) Matsui, T.; Koga, K. Tetrahedron Lett. 1978, 19, 1115-1118.
(19) Matsui, T.; Koga, K. Chem. Pham. Bull. 1979, 27, 2295-2303.
(20) Sasaki, S.; Shionoya, M.; Koga, K. J . Am. Chem. Soc. 1985, 107,
3371-3372.
* To whom correspondence should be addressed.
† University of Tsukuba.
‡ Gunma University.
X Abstract published in Advance ACS Abstracts, J une 1, 1996.
(1) Gokel, G. W.; Dishong, D. M.; Diamond, C. J . J . Chem. Soc.,
Chem. Commun. 1980, 1053-1054.
(2) Dishong, D. M.; Diamond, C. J .; Cinoman, M. I.; Gokel, G. W. J .
Am. Chem. Soc. 1983, 105, 586-593.
(3) Schultz, R. A.; White, B. D.; Dishong, D. M.; Arnold, K. A.; Gokel,
G. W. J . Am. Chem. Soc. 1985, 107, 6659-6668.
(4) Nakatsuji, Y.; Nakamura, T.; Yonetani, M.; Yuya, H.; Okahara,
M. J . Am. Chem. Soc. 1988, 110, 531-538.
(5) Izatt, R. M.; Bradshaw, J . S.; Nielsen, S. A.; Lamb, J . D.;
Christensen, J . J . Chem. Rev. 1985, 85, 271-339.
(6) Izatt, R. M.; Pawlak, K.; Bradshaw, J . S. Chem. Rev. 1991, 91,
1721-2085.
(7) White, B. D.; Mallen, J .; Arnold, K. A.; Fronczek, F. R.; Gandour,
R. D.; Gehrig, L. M. B.; Gokel, G. W. J . Org. Chem. 1989, 54, 937-
947.
(8) Kitazawa, S.; Kimura, K.; Yano, H.; Shono, T. J . Am. Chem. Soc.
1984, 106, 6978-6983.
(9) Strzelbicki, J .; Bartsch, R. A. Anal. Chem. 1981, 53, 1894-1899.
(10) Strzelbicki, J .; Bartsch, R. A. Anal. Chem. 1981, 53, 2247-2250.
(11) Strzelbicki, J .; Bartsch, R. A. Anal. Chem. 1981, 53, 2251-2253.
(12) Bartsch, R. A.; Heo, G. S.; Kang, S. I.; Liu, Y.; Strzelbicki, J . J .
Org. Chem. 1982, 47, 457-460.
(21) Behr, J . P.; Lehn, J . M. J . Chem. Soc., Chem. Commun. 1978,
143-146.
(22) Yano, Y.; Kimura, M.; Shimaoka, K.; Iwasaki, H. J . Chem. Soc.,
Chem. Commun. 1986, 160-161.
(23) Ohshima, S.; Tamura, N.; Nabeshima, T.; Yano, Y. J . Chem.
Soc., Chem. Commun. 1993, 712-713.
(24) Takaki, A.; Takano, M.; Ohshima, S.; Nabeshima, T.; Yano, Y.
Chem. Lett. 1994, 1417-1420.
(25) Craig, A. S.; Kataky, R.; Parker, D.; Adams, H.; Bailey, N.;
Schneider, H. J . Chem. Soc., Chem. Commun. 1989, 1870-1872.
(26) Craig, A. S.; Kataky, R.; Matthews, R. C.; Parker, D.; Ferguson,
G.; Lough, A.; Adams, H.; Bailey, N.; Schneider, H. J . Chem. Soc.,
Perkin Trans. 2 1990, 1523-1531.
(27) Bakker, W. I. I.; Verboom, W.; Reinhoudt, D. N. J . Chem. Soc.,
Chem. Commun. 1994, 71-72.
(28) Frensdorff, H. K. J . Am. Chem. Soc. 1971, 93, 600-606.
(29) Oue, M.; Akama, K.; Kimura, K.; Tanaka, M.; Shono, T. J .
Chem. Soc. Perkin Trans. 1 1989, 1675-1678.
(30) Oue, M.; Kimura, K.; Akama, K.; Tanaka, M.; Shono, T. Chem.
Lett. 1988, 409-410.
(13) Shoham, G.; Christianson, D. W.; Bartsch, R. A.; Heo, G. S.;
Olsher, U.; Lipscomb, W. N. J . Am. Chem. Soc. 1984, 106, 1280-1285.
(14) Tsukube, H.; Takagi, K.; Higashiyama, T.; Iwachido, T.; Haya-
ma, N. J . Chem. Soc., Perkin Trans. 1 1986, 1033-1037.
(31) Oue, M.; Kimura, K.; Shono, T. Anal. Chim. Acta 1987, 194,
293-298.
(32) Oue, M.; Kimura, K.; Shono, T. Analyst 1988, 113, 551-553.
S0022-3263(95)01761-0 CCC: $12.00 © 1996 American Chemical Society

Ag+ Extraction and Transport by Thiolariat Ethers
J . Org. Chem., Vol. 61, No. 13, 1996 4343
Sch em e 1
has also been achieved by redox reactions between thiol
and disulfide of crown ethers containing sulfur atoms33-35
and by metal coordination to change the conformation
of the binding site using pseudocrown ethers.36
Here we wish to report improved methods for the
preparation of various thiolariat ethers 1-6 and their
affinity toward metal ions. Thiolariat ethers with a 15-
crown-5 ring exhibit very high Ag+ selectivity compared
to other heavy metal ions during solvent extraction and
transport through a liquid membrane. The importance
of the synergistic coordination of the crown ring and the
sulfur atom outside the ring has also been proved by
extraction, transport, and NMR complexation studies.
This surprising effect, involving only one sulfide side arm,
on the binding preference of macrocycles promises ver-
satility of thiolariat ethers in the design of Ag+ binders
for various application, because of ease with which the
host molecules can be chemically modified.
Resu lts a n d Discu ssion
Syn th esis of Th iola r ia t Eth er s. We have previously
described a synthetic route to thiolariat ethers from 2,2-
dimethyl-1,3-dioxolane-4-methanol in seven steps (Scheme
1).37 The pathway is laborious and the overall yields are
low. Moreover, this route involves the preparation of
mercaptomethyl crown ethers 18 as intermediates which
are useful to functionalize the cyclic framework easily,
but is sensitive to autoxidation. Modification of the
synthetic method was undertaken to increase the reac-
tion yields and to reduce the number of reaction steps,
but not to decrease the usefulness for preparing various
thiolariat ethers.38 As shown in Scheme 2, sulfides 19
obtained by alkylation of thioglycerol by alkyl or benzyl
halide were treated with oligoethylene glycol ditosylate
(27) to give the corresponding thiolariat ethers 1-3.
Crown ethers (4, 5) containing [(2-methoxyethyl)thio]-
methyl and [[2-(benzylthio)ethyl]thio]methyl groups were
prepared from 2,2-dimethyl-1,3-dioxolane-4-methanol to-
sylate (23) (Scheme 3). Deprotection of ketals (25, 28)
under acidic conditions was carried out to give the
corresponding diols (26, 29). Cyclization reaction be-
tween the diols and ditosylate 27b was performed under
similar conditions to those for thiolariat ethers 2.38 Host
6, where length of the methylene spacer between the
We have recently synthesized thiolariat ethers, which
contain a sulfide group as a side chain, and found a
remarkably high Ag+ selectivity of thiolariat ethers
during solvent extraction.37,38 For metal binding, thio-
lariat ethers may possess an advantage over the crown
ethers containing a sulfur atom in the cyclic framework,
because the introduction of a sulfur atom into a crown
ring gives rise to an unfavorable entropic change upon
complexation with a metal ion.25,39
(33) Nabeshima, T.; Furusawa, H.; Yano, Y. Angew. Chem., Int. Ed.
Engl. 1994, 33, 1750-1751.
(34) Nabeshima, T.; Furusawa, H.; Yano, Y. Heterocycles 1994, 38,
2045-2050.
(35) Nabeshima, T.; Furusawa, H.; Tsukada, N.; Shinnai, T.;
Haruyama, T.; Yano, Y. Heterocycles 1995, 41, 655-659.
(36) Nabeshima, T.; Yosejima, I.; Yano, Y. Heterocycles 1994, 38,
1471-1474.
(37) Nabeshima, T.; Nishijima, K.; Tsukada, N.; Furusawa, H.;
Hosoya, T.; Yano, Y. J . Chem. Soc., Chem. Commun. 1992, 1092-1094.
(38) Nabeshima, T.; Tsukada, N.; Haruyama, T.; Yano, Y. Bull.
Chem. Soc. J pn. 1995, 68, 227-229.
(39) Wolf, R. E., J r.; Hartman, J . R.; Storey, J . M. E.; Foxman, B.
M.; Cooper, S. R. J . Am. Chem. Soc. 1987, 109, 4328-4335.

4344 J . Org. Chem., Vol. 61, No. 13, 1996
Nabeshima et al.
Sch em e 2
Sch em e 5
Sch em e 6
Sch em e 3
Ta ble 1. Solven t Extr a ction of Alk a li Meta l Ion s
extractability (%)a
Li+
Na+
K+
Rb+
Cs+
,
host
1a
2a
2b
2c
3a
4
1
3
3
2
16
18
21
22
22
14
6
6
4
4
5
1
19
23
22
93
24
10
6
17
18
7
10
1
1
15
15
17
82
22
12
9
-
9
-
-
57
10
6
3
-
-
-
-
1
9
10
11
12
13
14
15
16
17
none
4
9
-
-
5
Sch em e 4
3
13
10
12
1
17
84
0
-
-
2
3
6
7
3
-
-
61
0
21
29
0
20
94
0
0
a
Organic phase (CH2ClCH2Cl); [host] ) 1.0 × 10-4 M. Aqueous
phase; [metal picrate] ) 3.0 × 10-5 M and [metal chloride] ) 0.10
M.
the sulfoxide and sulfone analogs (9, 10) in good yields
(Scheme 6).
Solven t Extr a ction of Meta l Ion s. The affinities of
thiolariat ethers and the analogs toward metal ions were
examined by solvent extraction experiment using a 1,2-
dichloroethane-water biphasic system. For alkali metal
ions, an aqueous mixture of metal picrate (3.0 × 10-5 M)
and metal chloride (0.10 M) was employed as an aqueous
phase. A 1,2-dichloroethane solution of host (1.0 × 10-4
M) was used as an organic phase. The extractability of
each metal ion was estimated from the decrease of the
absorption (356 nm) of picrate anion in the aqueous
phase. According to the definition (see Experimental
Section), the value of the extractability is 100% when the
absorbance of the picrate anion is null. The results are
summarized in Table 1. The binding preference of
thiolariat ethers toward alkali metal ions is almost the
same as that of the corresponding lariat ethers. 12-
crown ring and the sulfur atom is longer than 1-5, was
obtained in a similar way (Scheme 4). Tosylate 31
obtained from alcohol 30 was not purified and reacted
directly with benzylmercaptan for preparation of sulfide
32, because 31 is easily hydrolyzed. After deprotection
the diol 33 was converted to the corresponding thiolariat
ether 6. The crown ethers (7, 8), with two side chains,
were also obtained via the cyclization of 27 and 36, where
the latter was prepared from diethyl (L)-tartarate in
several steps (Scheme 5). The thiolariat ether 2a was
oxidized with m-chloroperbenzoic acid (m-CPBA) to afford

Ag+ Extraction and Transport by Thiolariat Ethers
J . Org. Chem., Vol. 61, No. 13, 1996 4345
Ta ble 2. Solven t Extr a ction of Tr a n sition a n d Hea vy
Meta l Ion s
96% for 2a , 2b, and 2c, respectively) while, however,
showing very low affinity toward the other metal ions.
Compared to the thiolariat ethers, the corresponding
lariat ether 16, which has an ether chain instead of a
sulfide group, has much less affinity toward Ag+ (28%).
It is noteworthy that the Ag+ affinity is significantly
perturbed by only one sulfur atom, which does not exist
in the binding cavity but in the side chain.
An apparent ring-size effect of thiolariat ethers on the
Ag+ selectivity was observed. In 12-crown-4 derivative
1a , extractability for Ag+ drastically decreased (25%),
although Ag+ was extracted most preferentially among
the heavy metal ions examined here. The host 1a showed
a low affinity to all the heavy metal ions employed here.
In 18-crown-6 derivatives 3a and 3c, the Ag+ selectivity
also decreased considerably, because these hosts also
extracted Pb2+ effectively. This good affinity to Pb2+ is
to be expected from a 18-crown-6 framework, because a
similar tendency is observed for the 18-crown-6 deriva-
tives without a side chain.40 As in the case of 16, the
lariat ethers (15, 17) with a different cavity size exhibited
much lower extractability toward Ag+ than the corre-
sponding thiolariat ethers. These results also show the
importance of sulfur atom in the Ag+ selectivity. The 18-
crown-6 derivative 17 extracted both Ag+ and Pb2+ with
moderate extractability probably because of the 18-
crown-6 structure as described above.
extractability (%)a
host Ag+ Mn2+ Co2+ Ni2+ Cu2+ Zn2+ Cd2+ Pb2+
1a
2a
2b
2c
3a
3c
4
25
95
95
96
97
97
94
99
89
91
98
18
7
1
2
2
2
8
8
3
3
3
2
-
4
4
-
2
2
3
2
1
7
1
5
4
2
2
6
7
3
2
3
3
-
3
2
-
3
2
2
1
3
5
3
2
1
2
2
6
7
3
2
1
3
6
2
2
-
3
2
1
1
1
7
1
1
3
3
3
13
7
3
3
3
3
-
2
3
-
3
4
2
1
1
3
4
5
5
2
-
2
1
-
3
2
-
2
2
1
3
3
7
9
5
-
3
4
-
2
2
1
2
4
2
1
1
8
1
1
4
5
5
73
80
12
6
5
4
78
4
3
2
4
4
2
3
6
81
2
5
6
7
8
9
10
11
12
13
14
15
16
17
none
11
10
54
6
2
0
1
3
5
1
5
1
2
7
1
28
53
2
a
Organic phase (CH2ClCH2Cl); [host] ) 1.0 × 10-4 M. Aqueous
phase; [picric acid] ) 3.0 × 10-5 M and [metal nitrate] ) 0.01 M.
Crown-4 derivatives (1a , 15) showed very low extract-
ability toward Li+, Na+, K+, and Rb+. However, 15-
crown-5 (2a -c, 16) and 18-crown-6 (3a , 17) derivatives
extracted alkali metal ions more efficiently. Good selec-
tivity during solvent extraction between the Na+, K+, and
Rb+ ions was not observed with 15-crown-5 hosts. The
hosts 3a and 17, which contain a 18-crown-6 ring,
exhibited a characteristic preference order of extract-
ability to alkali metal ions (K+ > Rb+ > Cs+ > Na+). As
we expected, this preference reveals that the binding
ability toward alkali metal ions can be ascribed to the
affinity to the crown ring and that the side chains do not
contribute to the binding properties significantly. The
interaction between a sulfide group and an alkali metal
ion should be very weak. The extractability of the 15-
crown-5 derivatives, 9 and 10, is lower than that of the
corresponding thiolariat ethers. This decrease suggests
that an oxygen atom of the sulfoxide or sulfone group
prohibits coordination of a crown ring to alkali metal ions.
However, the [[2-(benzylthio)ethyl]thio]methyl and the
[(2-methoxyethyl)thio]methyl side chains do not affect the
binding behavior, probably because the hetero atoms are
located further from the binding cavity and thus can not
influence the coordination of alkali metal ions. During
the extraction of alkali metal ions, the usual ring size
dependency of the crown ethers on the alkali-metal-
binding selectivity was observed. Hence, the binding
preference results mainly from the affinity of each crown
ring. Moreover, the effect of the side chain containing a
sulfur atom on the extractability is small, if any, under
conditions employed here.
The neccessity of a cyclic structure for effective metal
binding was obviously supported by the lower extract-
ability (54%) of the linear polyether 13 compared to the
thiolariat ethers. Hence, synergistic coordination of the
ring oxygen and the sulfur atoms seems to be essential
for the selectivity. The host 13 still maintains Ag+
selectivity, while the extractability of the oxygen analog,
14, is much less (6%). Thus, in the linear systems only
one sulfur atom also affects Ag+ affinity efficiently.
Coordination of sulfur atom in the side chain of
thiolariat ethers was again proved to be very important
for Ag+ selectivity. In the sulfoxide and sulfone analogs,
9 and 10, the Ag+ extractability values are 18 and 7%,
respectively. These results clearly indicate that the
coordination of the lone pair(s) of the sulfur atom plays
an important role in Ag+ binding. Furthermore, the low
extractabilities of the benzocrown derivatives (11, 12)
suggest the significance of the coordination of the sulfide
group to Ag+ (vide infra). The decrease in the affinity of
the benzocrown hosts implies a 1:1 stoichiometry of the
Ag+ complexes of thiolariat ethers. It is not plausible
that one Ag+ is complexed with more than two hosts. If
two hosts bind one Ag+, a crown ring of one benzocrown
host and a sulfur atom of the other host may coordinate
Ag+ synergistically in a tail-to-head fashion. In this case,
the benzocrown derivatives (11, 12) might exhibit much
higher extractability. Upon 1:1 complexation, synergistic
coordination of the sulfur atom and the oxygen atoms of
the benzocrown ring cannot be performed. The CPK
model inspection suggested that the sulfur atom is forced
to be separate from the crown cavity. In compound 6 the
extractability of the Ag+ selectivity is slightly smaller
than 2. Probably the decrease is caused by the longer
spacer of 6 which is unfavorable for an effective syner-
gistic coordination involving both the oxygen and sulfur
atoms. In the thiolariat ethers (7, 8) bearing two sulfur
atoms in the side arms, the Ag+ affinity and selectivity
The extraction of heavy metal ions was carried out
using a mixture of picric acid (3.0 × 10-5 M) and metal
nitrate (0.01 M) as the aqueous phase and a 1,2-
dichloroethane solution containing the host (1.0 × 10-4
M) as the organic phase. The extractability was evalu-
ated according to a similar method using alkali metal
ions (Table 2). In contrast to the cases using alkali metal
ions, thiolariat ethers (2a -c) bearing a 15-crown-5 ring
exhibited remarkably high Ag+ selectivity. Some hosts
(2a -c) extracted Ag+ with high extractability (95, 95, and
(40) Lamb, J . D.; Izatt, R. M.; Robertson, P. A.; Christensen, J . J .
J . Am. Chem. Soc. 1980, 102, 2452-2454.

4346 J . Org. Chem., Vol. 61, No. 13, 1996
Nabeshima et al.
Ta ble 3. Tr a n sp or t of Hea vy Meta l Ion s by Th iola r ia t
Eth er s
Ta ble 4. Tr a n sp or t of Tr a n sition a n d Hea vy Meta l Ion s
by 2a a n d 3a
concn of metal ion in the receiving phase (M) (after 30 h)a
[metal ion]
in the receiving phase
host
Ag+
Cu2+
Cd2+
Pb2+
(× 10-5 M) (after 24 h)
2a
2c
3a
3c
4
5
7
9
8.0 × 10-4
8.5 × × 10-4
1.2 × 10-3
1.1 × 10-3
7.2 × 10-4
1.3 × 10-3
9.2 × 10-4
4.7 × 10-5
1.8 × 10-5
1.2 × 10-4
1.2 × 10-4
0
0
-
0
0
-
0
0
0
-
-
0
0
-
-
0
-
0
0
0
0
0
conditionsa
host
Ag+ Cu2+ Cd2+ Pb2+
1.7 × 10-3
noncompetitive transportb 2a
7.7
20
0
0
0
0
0
0
0
-
0
0
0
0
26
0
1.2 × 10-3
3a
none
2a
3a
none
0
0
0
0
0
0
0
19
25
0
competitive transportc
0
58
0
0
10
16
17
Organic phase (CH2ClCH2Cl) 50 mL: [host] ) 2 × 10-4 M.
a
0
-
b
Source phase (distilled H2O) 4 mL: [metal nitrate] ) 0.01 M.
1.6 × 10-3
c [AgNO3] ) [Cu(NO3)2] ) [Cd(NO3)2] ) [Pb(NO3)2] ) 0.01 M.
Organic phase (CH2ClCH2Cl) 50 mL; [host] ) 2.0 × 10-4 M.
a
Source phase (distilled H2O) 4 mL; [metal nitrate] ) 0.10 M.
remain high. Existence of two side chains did not affect
the binding behavior, probably because only one side
chain can coordinate to the Ag+ ion captured in the crown
ring. The cationic radius of Ag+ is between those of Na+
and K+.5 Accordingly, upon complexation of Ag+ with the
thiolariat ethers bearing a 15-crown-5 ring, Ag+ is
considered to be slightly outside the cavity and, hence,
to be coordinated by the sulfur atom in close proximity
to the ring.
Tr a n sp or t of Meta l Ion s th r ou gh a Liqu id Mem -
br a n e. The metal transport ability of thiolariat ethers
was evaluated by a transport experiment across a 1,2-
dichloroethane layer as a liquid membrane using a dual
cylindrical cell.41 Ag+, Cu2+, Cd2+, and Pb2+ ions were
used for the transport experiment. The source phase was
a 0.10 M aqueous solution of metal nitrate, and the
receiving phase consisted of deionized water. The organic
layer was a 1,2-dichloroethane solution containing the
host (2.0 × 10-4 M). The concentrations of metal ions
transported into the receiving phase were determined by
atomic absorption spectroscopy. The metal ion concen-
trations after 30 h are summarized in Table 3.
F igu r e 1. Schematic illustration of Ag+ complex of thiolariat
ether.
of the transport. However, the Pb2+ selectivity of 3a in
the competitive transport is higher than that in the single
ion transport. This can be attributed to the predominant
occupation of the 18-crown-6 cavity with Pb2+, so that
the amounts of the cavity available for Ag+ binding
decreased.
In both noncompetitive and competitive transport of
metal ions, very high Ag+ selectivity was achieved by
thiolariat ethers (2a , 2c, 4, 5) with a 15-crown-5 ring.
The synergistic coordination of the sulfur and oxygen
atoms of the carriers was strongly supported by the
transport experiments as in the case of the solvent
extraction studies.
In the thiolariat ethers (2a , 2c, 4, 5) a remarkably high
Ag+ selectivity was achieved in the metal ion transport
as for the solvent extractions. The thiolariat ethers
bearing a 15-crown-5 ring only carried Ag+ effectively.
No other metal ions were detected, within experimental
errors, in the receiving phase after 30 h. In contrast,
thiolariat ethers (3a , 3c) with a 18-crown-6 ring trans-
ported both Pb2+ and Ag+ efficiently. In the case of 3a
Pb2+ was carried more predominantly than Ag+. This
Pb2+ affinity probably results from the binding properties
of a 18-crown-6 ring (vide supra). Much smaller amounts
of Ag+ were transported by the sulfoxide, sulfone analogs
9, 10, and lariat ether 16. These results indicate the
importance of the coordination of the side arm sulfur
atom in Ag+ selectivity, as seen with the solvent extrac-
tion. The coordination of one side chain is sufficient for
high Ag+ selectivity, because in host 7 an amount of Ag+
comparable to that in 2a , 2c, 4, and 5 was transported.
In competitive transport experiments using an aqueous
mixture of Ag+, Cu2+, Cd2+, and Pb2+ (0.01 M each) as a
source phase, apparent enhancement of Ag+ concentra-
tion and selectivity in the receiving phase was performed
in 15-crown-5 derivative 2a , compared to single ion
transport (Table 4, a 0.01 M metal nitrate solution for
the source phase). This change was probably caused by
the increase in the total metal ion concentration of the
source phase, because the concentration gradient be-
tween the receiving and source phases is a driving force
Only one sulfur atom of each of the thiolariat ethers
can coordinate to the Ag+. Surprisingly, the sulfur atom
affects both the extraction and transport selectivity
enormously, although the atom is located outside the
cyclic recognition site. However, the synergistic coordi-
nation is performed probably by the vicinity of the sulfur
atom to the ring and due to ring size of a 15-crown-5
framework which is slightly smaller than the ionic
diameter of Ag+. The plausible structure of the Ag+
complex is illustrated in Figure 1.
Sp ectr a l Ch a n ges of 1H a n d 13C NMR of Th iola r ia t
Eth er on th e Ad d ition of Ag+. The synergistic coor-
dination of the oxygen and sulfur atoms in thiolariat
ether 2c to Ag+ is strongly supported by 1H and 13C NMR
spectroscopy results. The 1H NMR resonances of two sets
of methylene protons (HR, Hâ) adjacent to the sulfur
atom were shifted noticeably to lower field (2.552 to 2.780
ppm and 2.637 to 2.999 ppm for HR and Hâ, respectively,
in CDCl3-CD3CN (9:1)), when 1 equiv of AgNO3 was
added. However, the chemical shift of the methyl protons
of the dodecyl chain did not change significantly. Obvi-
ous but complicated changes were observed in methylene
protons of the crown ring. These changes suggest that
both the ring oxygen and the sulfur atoms in the side
chain coordinate to the Ag+ simultaneously. The J ob plot
using a resonance of HR for complexation between 2c and
Ag+ has a maximum at a mole fraction of 0.5 indicative
of formation of a 1:1 complex (Figure 2). A nonlinear-

Ag+ Extraction and Transport by Thiolariat Ethers
J . Org. Chem., Vol. 61, No. 13, 1996 4347
We are currently preparing suitable crystals of the
complex for X-ray crystallography.
Con clu sion
Thiolariat ethers bearing a 15-crown-5 ring exhibit
remarkably high Ag+ selectivity in solvent extraction and
metal ion transport experiments. The results strongly
suggested that the selectivity results from the synergistic
coordination of the oxygen atoms of the appropriate
crown ring size and sulfur atom to Ag+. It is noteworthy
that this tremendous perturbation of metal binding
preference of crown ethers is caused by only one sulfur
atom in the vicinity of the cavity, although the atom is
located outside the cyclic framework.
Benzylsulfenyl derivatives (1a , 2a , 3a ) are converted
to the corresponding mercatomethyl crown ethers whose
functionality is easily modified. Thus, the thiolariat
ether frameworks can be combined with different func-
tional moieties to prepare novel functional molecular
systems. Preparation of various polymer-supporting
materials which are useful to separate Ag+ may be
performed. Moreover diverse technological applications
to utilize thiolariat ethers as functionalized materials for
Ag+ binder in the photographic technology and for the
concentration and recovery of Ag+ ions from industrial
waste water are also promised.
F igu r e 2. Plot (J ob) of [2c-Ag+ complex] versus the mole
fraction [2c]/([2c] + [Ag+]) at constant [2c] + [Ag+].
Exp er im en ta l Section
General methods were previously reported.41
N
4-[[(2-Hyd r oxyeth yl)th io]m eth yl]-2,2-d im eth yl-1,3-d i-
oxola n e (24). 2-Mercaptoethanol (5 mL, 71.3 mmol) and
tosylate 23 (20.2 g, 70.5 mmol) were added successively to a
solution of NaOH (3.41 g, 80.9 mmol) in 95% EtOH (100 mL)
and THF (8 mL) under nitrogen. The reaction mixture was
refluxed for 10 h. After cooling, the solvent was evaporated
in vacuo. The residue thus obtained was mixed with 60 mL
of water and then extracted with CH2Cl2 (60 mL × 3). The
organic layer was washed with water, dried over anhydrous
MgSO4, and concentrated in vacuo. The crude product was
purified by molecular distillation (150 °C, 2 mmHg) to give
24 as a colorless oil (10.8 g, 56.4 mol) in 80% yield: 1H NMR
(400 MHz, CDCl3) 1.371 (s, 3H), 1.449 (s, 3H), 2.47 (t, J ) 5.8
Hz, 1H), 2.69 (dd, J ) 6.2, 14 Hz, 1H), 2.73-2.87 (m, 3H), 3.72
(dd, J ) 6.5, 8.4 Hz, 1H), 3.69-3.82 (m, 2H), 4.11 (dd, J ) 6.1,
8.4 Hz, 1H), 4.279 (quint, J ) 6.2 Hz, 1H); 13C NMR (50 MHz,
CDCl3) 25.61, 26.91, 35.03, 36.04, 61.14, 68.93, 75.86, 110.00;
IR (neat) 3438 (br), 2985, 2932, 2876, 1455, 1407, 1380, 1371,
1254, 1215, 1153, 1060, 863, 843; MS (40 eV) m/ e 192(M+,
0.7%), 177(14.8), 174(19.1), 159(3.6), 134(9.1), 117(23.4), 101-
(100). HRMS (EI): calcd for C8H16O3S 192.0820, found
192.0863.
4-[[(2-Meth oxyeth yl)th io]m eth yl]-2,2-d im eth yl-1,3-d i-
oxola n e (25). To a suspension of NaH (2.72 g, 62.4 mmol) in
30 mL of THF was added a solution of ketal 24 (10.8 g, 56.4
mmol) in 23 mL of THF under nitrogen. After stirring for
several minutes at room temperature, methyl iodide (3.5 mL,
56 mmol) was added to the reaction mixture. The mixture
was refluxed for 10 h and then concentrated in vacuo. The
residue thus obtained was mixed with 80 mL of water and
extracted with CH2Cl2 (80 mL × 3). The organic layer was
washed twice with water and dried over anhydrous MgSO4.
The crude product obtained after evaporation of the solvent
was purified by Kugelrohr distillation (110 °C, 3 mmHg) to
give 25 (10.7 g, 51.5 mmol) in 92% yield: 1H NMR (200
MHz, CDCl3) 1.36 (s, 3H), 1.44 (s, 3H), 2.61-2.87 (m, 4H), 3.37
(s, 3H), 3.57 (t, J ) 6.5 Hz, 2H), 3.73 (dd, J ) 6, 8 Hz, 1H),
4.12 (dd, J ) 6, 8 Hz, 1H), 4.20-4.34 (m, 1H); 13C NMR
N
10
F igu r e 3. 1H NMR titration for complexation between thio-
lariat ether 2c and Ag+ ([2c] ) 3 × 10-3 M).
1
least-square analysis of a H NMR titration curve using
a resonance of HR protons gave the stability constants
between 2c and Ag+ of 1700 M-1 in 3% CD3CN-CDCl3
and of 1100 M-1 in 10% CD3CN-CDCl3 (Figure 3). The
infinite δ values calculated are 2.88 ppm and 2.84 ppm,
respectively.
In 13C NMR definite changes of the resonances of 2c
were observed when mixed with 1 equiv of AgNO3 (Table
5). The signals of carbons (C4, C5) adjacent to the sulfur
atoms were apparently affected (downfield shifts, 2.354,
2.313 ppm, respectively). Changes in the chemical shifts
of the ring carbons were also observed. The signal of C6
bearing a side chain was shifted most significantly to the
higher field (∆δ ) -2.822 ppm) compared to the other
ring carbons. In addition, C7 and C8 (assigned tenta-
tively) carbons which exist near C6 were also affected
(∆δ ) -0.977, -0.886 ppm). These changes are probably
explained in terms of (1) metal-dipole interaction upon
ligation of a crown ring to Ag+ and (2) the conformational
change of 2c induced by the coordination of sulfur atom
to Ag+. Therefore, NMR spectroscopic examination
performed here was in accordance with the synergistic
coordination of a crown ring and a sulfur atom in the
side arm to give a 1:1 complex between a thiolariat ether
and Ag+ in a fashion shown in Figure 1.
Elucidation of the crystal structure of the complex is
important and useful to clarify reasons for the effective
and selective coordination of a thiolariat ether to Ag+.
(41) Nabeshima, T.; Inaba, T.; Furukawa, N.; Hosoya, T.; Yano, Y.
Inorg. Chem. 1993, 32, 1407-1416.

4348 J . Org. Chem., Vol. 61, No. 13, 1996
Nabeshima et al.
Ta ble 5. Ch a n ges of 13C NMR Ch em ica l Sh ifts of Th iola r ia t Eth er (2c) by th e Ad d ition of Ag+ (1 equ iv)
(50 MHz, CDCl3) 25.64, 27.02, 32.26, 35.72, 58.91, 69.07, 72.40,
75.87, 109.87; IR (neat) 2985, 2928, 2875, 1456, 1370, 1216,
1154, 1116, 1060, 960, 1060, 960, 915, 863. HRMS (EI): calcd
for C9H18O3S 206.0977, found 206.0960.
methanol-3 N HCl (5:2, v/v) at room temperature. The
resultant precipitates were collected by suction filtration, and
dried in vacuo to give 4.77 g (18.5 mmol, 88%) of desired diol
29 as a pale yellow powder, which was used without further
purification in the next step. An analytically pure sample was
prepared by recrystallization from n-hexane: mp 52-54 °C.
1H NMR (200 MHz, CDCl3) 1.97 (t, J ) 5.1 Hz, 1H), 2.50-
2.78 (m, 7H), 3.45-3.60 (m, 1H), 3.65-3.75 (m, 2H), 3.76 (s,
2H), 7.2-7.4 (m, 5H); 13C NMR (50 MHz, CDCl3) 31.38, 32.28,
35.72, 35.84, 36.48, 65.46, 70.66, 127.56, 128.98, 129.25,
138.43; IR (KBr) 3312 (br), 2915, 1558, 1493, 1453, 1435, 1420,
1418, 1338, 1300, 1244, 1208, 1197, 1164, 1126, 1108, 1068,
1035, 1022, 1010, 955, 927, 896, 876, 806, 776, 744, 729, 697.
MS m/ e 258 (M+). Anal. Calcd for C12H18O2S2: C, 55.78, H,
7.02. Found: C, 55.45, H, 6.87.
[[[2-(Ben zylth io)eth yl]th io]m eth yl]-15-cr own -5 (5). Diol
29 (2.00 g, 7.76 mmol) was added to a suspension of NaH
(0.804 g, 18.4 mmol) in 20 mL of THF under nitrogen. To the
mixture was added 27b (4.05 g, 8.05 mmol) in 20 mL of THF
by a syringe. The mixture was refluxed for 15 h and then
concentrated in vacuo. The residue thus obtained was mixed
with water and extracted with CH2Cl2. The organic layer was
dried over MgSO4. The crude product after evaporation of the
solvent was purified by silica gel column chromatography
(ethyl acetate) to give 5 (1.94 g, 4.65 mmol) as a yellow oil in
60% yield: 1H NMR (200 MHz, CDCl3) 2.5-2.8 (m, 6H), 3.5-
3.9 (m, 19H), 3.74 (s, 2H), 7.2-7.4 (m, 5H); 13C NMR (50 MHz,
CDCl3) 13.74, 22.04, 31.89, 32.87, 34.02, 70.43, 70.69, 70.75,
70.95, 71.10, 71.25, 72.93, 79.78; IR (neat) 3060, 3024, 2904,
2864, 1702, 1600, 1496, 1454, 1422, 1354, 1292, 1250, 1204,
1198, 1134, 1122, 986, 944, 938, 868, 840, 768, 700. HRMS
(EI): calcd for C20H32O5S2 416.1691, found 416.1715.
4-[3-(Ben zylth io)pr opyl]-2,2-dim eth yl-1,3-dioxolan e (32).
To a solution of DL-1,2-O-isopropylidenepentane-1,2,5-triol
(30)42 (2.50 g, 15.6 mmol) in 45 mL of pyridine was added 3.00
g (15.7 mmol) of tosyl chloride in 20 mL of pyridine so slowly
(ca. 30 min) on an ice-salt bath that the temperature of the
reaction mixture was kept below 0 °C. After stirring for
additional 3 h at 0 °C, the mixture was concentrated very
carefully at room temperature using a vacuum pump with a
liquid N2 trap to avoid decomposition of the tosylate. To the
residue thus obtained were added NaH (0.757 g, 17.3 mmol),
benzyl mercaptan (2.13 g, 17.2 mmol), and 50 mL of THF. The
mixture was stirred for 18 h at room temperature and then
concentrated in vacuo. The residue was mixed with 50 mL of
water and extracted with CHCl3 (50 mL × 4). The organic
layers were combined and washed with water (150 mL × 3).
The organic layer was dried over anhydrous MgSO4 and
concentrated in vacuo. The crude product was purified by
silica gel column chromatography (CH2Cl2) to give 32 (1.81 g,
6.79 mmol) in 44% yield: 1H NMR (200 MHz, CDCl3) 1.34 (s,
3H), 1.40 (s, 3H), 1.50-1.75 (m, 4H), 2.45 (t, J ) 7.0 Hz, 2H),
1-[[(2-Meth oxyeth yl)th io]m eth yl]-2,3-p r op a n ed iol (26).
Ketal 25 (2.36 g, 11.4 mmol) was treated with 35 mL of
methanol-3 N HCl (5:2, v/v) for 2 h at room temperature. The
reaction mixture was concentrated in vacuo. The residue thus
obtained was mixed with water and then extracted with
CHCl3. The organic layer was dried over anhydrous MgSO4.
After evaporation of the solvent, 26 was obtained as a pale
yellow oil (1.00 g, 6.02 mmol) in 53% yield. The crude product
was pure enough for the preparation of 4. Very pure 4 was
afforded by silica gel column chromatography (CHCl3-MeOH,
20:1, v/v): 1H NMR (200 MHz, CDCl3) 2.58-2.83 (m, 6H), 3.39
(s, 3H), 3.51-3.64 (m, 3H), 3.68-3.89 (m, 2H); 13C NMR (50
MHz, CDCl3) 32.28, 36.25, 58.91, 65.50, 71.25, 72.44; IR 3400
(br), 2928, 2834, 1640, 1454, 1410, 1383, 1294, 1216, 1190,
1098, 1036, 957, 884. HRMS (EI): calcd for C6H14O3S 166.0664,
found 166.0656.
[[(2-Met h oxyet h yl)t h io]m et h yl]-15-cr ow n -5 (4). Ac-
cording to a similar procedure for preparation of 2a ,38 diol 26
(0.814 g, 4.90 mmol) was treated with tetraethylene glycol
ditosylate (27b) (2.47 g, 4.92 mmol) and NaH (0.477 g, 10.9
mmol) in 25 mL of THF. The crude product was purified by
flash column chromatography (SiO2, CHCl3) to give 4 (0.222
g, 0.684 mol) in 14% yield: 1H NMR (200 MHz, CDCl3) 2.71
(d, J ) 5.3 Hz, 2H), 2.76 (t, J ) 6.6 Hz, 2H), 3.37 (s, 3H), 3.56
(t, 6.6 Hz, 2H), 3.62-3.84 (m, 19H); 13C NMR (125 MHz,
CDCl3) 32.38, 34.37, 58.71, 70.29, 70.47, 70.49, 70.56, 70.59,
70.80, 70.90, 71.08, 72.18, 72.61, 79.63; IR (neat) 2866, 1450,
1349, 1250, 1122, 985, 941, 869, 839. HRMS (EI): calcd for
C14H28O6S 324.16066, found 324.15897.
4-[[[2-(Ben zylth io)eth yl]th io]m eth yl]-2,2-d im eth yl-1,3-
d ioxola n e (28). To a solution of NaOH (1.34 g, 31.8 mmol)
in 95% EtOH (42 mL)-THF (3 mL) were added 2-(benzylthio)-
ethylmercaptan (6.88 g, 28.0 mmol) and 23 (8.65 g, 30.2 mmol).
The mixture was refluxed overnight and then concentrated
in vacuo. The residue thus obtained was mixed with 60 mL
of water, and the mixture was extracted with CH2Cl2 (60 mL
× 3). The organic layer was washed with water and dried over
anhydrous MgSO4. The crude product obtained after evapora-
tion of the solvent was purified by silica gel flash column
chromatography (CHCl3-n-hexane, 6:5, v/v) to give a pale
yellow oil (8.63 g, 28.9 mmol) in 96% yield: 1H NMR (200 MHz,
CDCl3) 1.35 (s, 3H), 1.41 (s, 3H), 2.5-2.8 (m, 6H), 3.67 (dd, J
) 5, 7 Hz, 1H), 3.74 (s, 2H), 4.07 (dd, J ) 5, 7 Hz, 1H), 4.10-
4.25 (m, 1H), 7.21-7.32 (m, 5H); 13C NMR (125 MHz, CDCl3)
25.55, 26.93, 31.35, 32.46, 35.25, 36.41, 68.84, 75.57, 109.61,
127.17, 128.60, 128.85, 138.12; IR (neat) 2984, 2928, 2875,
1494, 1453, 1422, 1379, 1369, 1212, 1153, 1060, 862, 770, 700.
MS m/ e 298 (M+). Anal. Calcd for C15H22O2S2: C, 60.37, H,
7.43. Found: C, 60.11, H, 7.42.
1-[[2-(Ben zylth io)eth yl]th io]-2,3-pr opa n ediol (29). Ket-
al 28 (6.24 g, 20.9 mmol) was mixed overnight with 70 mL of
(42) Hayashi, H.; Nakanishi, K.; Brandon, C.; Marmur, J . J . Am.
Chem. Soc. 1973, 95, 8749-8757.

Ag+ Extraction and Transport by Thiolariat Ethers
J . Org. Chem., Vol. 61, No. 13, 1996 4349
3.45-3.52 (m, 1H), 3.71 (s, 2H), 3.96-4.15 (m, 2H), 7.15-7.45
(m, 5H); 13C NMR (50 MHz, CDCl3) 25.45, 25.77, 27.01, 31.24,
32.72, 36.28, 69.51, 75.76, 109.03, 127.27, 128.81, 129.17,
138.89; IR (neat) 3411 (br), 3084, 3061, 1494, 1453, 1378, 1369,
1241, 1215, 1069, 858, 769, 702; MS (EI) m/ e 266(M+, 0.6%),
251(6.8), 208(25), 117(40.1), 91(100). HRMS (EI): calcd for
C15H22O2S 266.1341, found 266.1390.
5-(Ben zylth io)-1,2-p en ta n ed iol (33). According to a pro-
cedure similar to the preparation of 26, a mixture of ketal 32
(0.889 g, 3.34 mmol) and 21 mL of methanol-3 N HCl (5:2,
v/v) was stirred for 20 min at room temperature. The crude
product obtained after evaporation was purified by silica gel
chromatography using CH2Cl2 to afford 33 (0.651 g, 2.88 mmol)
in 86% yield as a pale yellow oil: 1H NMR (200 MHz, CDCl3)
1.4-1.9 (m, 4H), 2.15 (br, 1H), 2.35 (br, 1H), 2.45 (t, J ) 7.1
Hz, 2H), 3.3-3.5 (m, 1H), 3.5-3.7 (m, 2H), 3.71 (s, 2H), 7.2-
7.4 (m, 5H); 13C NMR (50 MHz, CDCl3) 25.21, 31.37, 32.14,
36.35, 66.83, 72.01, 127.31, 128.84, 129.19, 138.85; IR (neat)
3372 (br), 3026, 2934, 1493, 1452, 1239, 1071, 869, 770, 701.
HRMS (EI): calcd for C12H18O2S 226.1028, found 226.1024.
2H), 3.5-3.9 (m, 18H), 3.74 (s, 4H), 7.15-7.4 (m, 10H); 13C
NMR (50 MHz, CDCl3-CD3CN ) 9:1, v/v) 32.05, 36.98, 70.57,
70.77, 71.18, 71.77, 80.54, 127.35, 128.87, 129.44, 139.01; IR
(neat) 3060, 3024, 2912, 2864, 1602, 1494, 1454, 1422, 1406,
1350, 1296, 1242, 1126, 1118, 1046, 1030, 990, 936, 834, 768,
702; HRMS (EI): calcd for C26H36O5S2 492.2004, found 492.1982.
Bis[(ben zylth io)m eth yl]-18-cr ow n -8 (8). According to a
procedure similar to that for 2c,38 host 8 was prepared from
diol 36 (0.994 g, 2.97 mmol), pentaethylene glycol ditosylate
(27c) (1.70 g, 3.12 mmol), and NaH (0.283 g, 6.49 mmol) in 14
mL of THF. The crude product was purified by silica gel
column chromatography using ethyl acetate as eluent to give
8 (0.449 g, 0.837 mmol) as a pale yellow oil in 28% yield: 1H
NMR (200 MHz, CDCl3) 2.51 (dd, J ) 7, 14 Hz, 2H), 2.67 (dd,
J ) 5, 14 Hz, 2H), 3.5-3.8 (m, 22H), 3.74 (s, 4H), 7.2-7.35
(m, 10H); 13C NMR (125 MHz, CDCl3) 31.51, 36.85, 70.54,
70.64, 70.68, 70.76, 70.86, 79.85, 126.96, 128.46, 129.00,
138.48; IR (neat) 3060, 3028, 2908, 2872, 1700, 1600, 1494,
1454, 1420, 1352, 1292, 1250, 1128, 1114, 1030, 994, 948, 844,
766, 700; MS (FAB) 559 ([M + Na]+), 537 ([M + H]+). HRMS
(EI): calcd for C28H40O6S2 536.2266, found 536.2245.
[(Ben zylsu lfin yl)m eth yl]-15-cr ow n -5 (9). To a methyl-
ene chloride (40 mL) solution of [(benzylthio)methyl]-15-crown-
5 (2a ) (1.50 g, 4.21 mmol) was added 1 equiv of m-CPBA (ca.
4.2 mmol) at -10 °C. The mixture was stirred for 5 h below
-10 °C, and then NH3 gas was bubbled into the mixture. After
the precipitates thus obtained were filtered off, the filtrate was
concentrated in vacuo. The residue was purified by silica gel
column chromatography (CH2Cl2-methanol ) 20:1, v/v) to give
9 (1.50 g, 4.03 mmol) as a pale yellow oil in 96% yield: 1H
NMR (200 MHz, CDCl3) 2.67-3.06 (m, 2H), 3.5-3.9 (m, 18H),
3.95-4.2 (m, 3H), 7.2-7.4 (m, 5H); 13C NMR (50 MHz, CDCl3)
52.49, 55.47, 58.53, 59.14, 69.96, 70.57, 70.68, 70.73, 70.95,
71.12, 72.27, 72.68, 73.69, 73.82, 77.53, 128.63, 129.24, 130.40,
130.51, 130.67; IR (neat) 2904, 2864, 1496, 1456, 1408, 1356,
1296, 1250, 1128, 1118, 1040, 988, 942, 862, 840, 752, 700,
664. Anal. Calcd for C18H28O6S: C, 58.04, H, 7.58. Found:
C, 57.78, H, 7.77.
[(Ben zylsu lfon yl)m eth yl]-15-cr ow n -5 (10). Compound
2a (1.50 g, 4.21 mmol) was reacted with 2 equiv of m-CPBA
(ca. 8.4 mmol) in the presence of K2CO3 (0.623 g, 4.51 mmol)
in 80 mL of CH2Cl2 below -10 °C for 6 h. NH3 gas was bubbled
into the mixture, and then the resultant precipitates were
filtered off. The filtrate was then concentrated in vacuo. The
crude product was purified column chromatography (SiO2,
CH2Cl2-methanol ) 20:1, v/v) to give 10 (1.39 g, 3.59 mmol)
as a pale yellow oil in 85% yield: 1H NMR (200 MHz, CDCl3)
2.98 (d, J ) 15 Hz, 1H), 3.28 (dd, J ) 9.6, 15 Hz, 1H), 3.5-4.0
(m, 16H), 4.1-4.2 (m, 1H), 4.26 (d, J ) 14 Hz, 1H), 4.40 (d, J
) 14 Hz, 1H), 7.3-7.5 (m, 5H); 13C NMR (50 MHz, CDCl3)
53.85, 61.29, 70.46, 70.61, 70.71, 70.79, 70.95, 71.06, 71.32,
71.86, 75.12, 77.53, 128.60, 129.18, 131.55; IR (neat) 2904,
2868, 1496, 1456, 1396, 1356, 1300, 1256, 1200, 1132, 1118,
988, 938, 872, 830, 760, 700, 666. Anal. Calcd for C18H28O7S:
C, 55.65, H, 7.26. Found: C, 55.29, H, 7.24.
Solven t Extr a ction . The extraction of metal ions from the
aqueous solution into 1,2-dichloroethane was performed in
capped vials. After the biphasic mixture (the volumes of the
aqueous and organic phases are 10 mL each) was stirred
vigorously for 6 h at 25 ( 1 °C, the amounts of picrate anion
in the aqueous phase were determined by UV-VIS spectros-
copy monitoring at 356 nm. The extractability was calculated
according to eq 1. All experiments were carried out in
duplicate or triplicate and the respective results were aver-
aged.
[3-(Ben zylth io)p r op yl]-15-cr ow n -5 (6). According to a
procedure similar to that for 2a , host 6 was prepared from
NaH (0.278g, 6.37 mmol), diol 33 (0.638 g, 2.82 mmol), and
27b (1.45 g, 2.89 mmol) in 40 mL of THF. The crude product
was purified by silica gel column chromatography (ethyl
acetate) to give 6 (0.333 g, 0.866 mmol) in 31% as a yellow oil:
1H NMR (200 MHz, CDCl3) 1.45-1.8 (m, 4H), 2.43 (t, J ) 7.2
Hz, 2H), 3.4-3.8 (m, 19H), 3.70 (s, 2H), 7.2-7.35 (m, 5H); 13
C
NMR (125 MHz, CDCl3) 25.29, 31.25, 31.44, 36.26, 70.05,
70.50, 70.51, 70.60, 70.75, 71.02, 71.05, 74.14, 79.17, 126.89,
128.46, 128.82, 138.60; IR (neat) 3059, 3026, 2908, 2861, 1494,
1453, 1354, 1293, 1249, 1124, 984, 939, 855, 770, 703. HRMS
(EI): calcd for C19H30O5S 370.1814, found 370.1809.
(-)-tr a n s-4,5-Bis[(ben zylth io)m eth yl]-2,2-d im eth yl-1,3-
d ioxola n e (35). A mixture of benzylmercaptan (2.39 mL, 20.4
mmol), ditosylate 3443 (4.56 g, 9.68 mmol), and NaOH (1.04 g,
24.7 mmol) in 30 mL of 95% ethanol and 4.5 mL of THF was
refluxed overnight. After cooling, the mixture was concen-
trated in vacuo, suspended in water, and then extracted with
CH2Cl2 three times. The combined organic layer was washed
with water, dried over anhydrous MgSO4, and concentrated
in vacuo. The residue thus obtained was chromatographed
on silica gel using CH2Cl2-n-hexane (7:3, v/v) as eluent to give
35 (3.32 g, 8.87 mmol) in 92% as a pale orange oil: 1H NMR
(400 MHz, CDCl3) 1.408 (s, 6H), 2.54-2.67 (m, 4H), 3.71-3.82
(m, 4H), 3.85-3.92 (m, 2H), 7.2-7.3 (m, 10H); 13C NMR (125
MHz, CDCl3) 27.25, 33.38, 36.87, 79.81, 109.24, 127.10, 128.52,
129.05, 138.11; IR (neat) 3060, 3027, 2984, 2914, 2867, 1601,
1494, 1453, 1379, 1370, 1237, 1163, 1100, 1071, 1050, 1028,
901, 770, 747, 700. MS m/ e 374 (M+). Anal. Calcd for
C21H26O2S2: C, 67.34, H, 7.00. Found: C, 67.17, H, 7.06.
1,4-Bis(ben zylth io)-2,3-bu ta n ed iol (36). A mixture of
ketal 35 (3.44 g, 9.26 mmol), 42 mL of methanol-6 N HCl (5:
2, v/v), and 8 mL of THF was stirred for 6 h at room
temperature to give precipitates. The precipitates were col-
lected by suction filtration, washed with water, and then
recrystallized from n-hexane-CHCl3-ethanol to afford 36
(2.79 g, 8.34 mmol) in 90% yield as pale yellow crystals: mp
105-106 °C. 1H NMR (200 MHz, CDCl3) 2.5-2.6 (m, 6H),
3.5-3.65 (m, 2H), 3.73 (s, 4H), 7.2-7.35 (m, 10H); 13C NMR
(125 MHz, CDCl3) 35.30, 36.42, 70.58, 127.24, 128.63, 128.92,
137.98; IR (KBr) 3212(br), 2916, 1452, 1095, 1044, 1019, 931,
913, 894, 768, 706. MS m/ e 334 (M+). Anal. Calcd for
C18H22O2S2: C, 64.64, H, 6.63. Found: C, 64.49, H, 6.65.
Bis[(ben zylth io)m eth yl]-15-cr ow n -5 (7). According to a
procedure similar to that for 2a , host 7 was prepared from
diol 36 (1.03 g, 3.07 mmol), 27b (1.62 g, 3.23 mmol), and NaH
(0.285 g, 6.53 mmol) in 18 mL of THF. The crude product was
purified by silica gel column chromatography using ethyl
acetate-n-hexane (1:1, v/v) as eluent to give 7 (0.700 g, 1.42
mmol) as a colorless oil in 46% yield: 1H NMR (200 MHz,
CDCl3) 2.39 (dd, J ) 8, 13 Hz, 2H), 2.64 (dd, J ) 3, 13 Hz,
extractability (%) ) ([Pic-]aq,0 - [Pic-])/[Pic-]aq,0 × 100
(1)
where [Pic-]aq,0 is the initial concentration of picrate in the
aqueous phase (3 × 10-5 M), and [Pic-] is the concentration of
picrate in the aqueous phase after extraction.
Tr a n sp or t th r ou gh a Liqu id Mem br a n e. An apparatus
(a dual cylindric cell) for the transport experiment across liquid
membrane41 was designed on the basis of that of Lamb et al.44
(43) Rubin, L. J .; Lardy, H. A.; Fischer, H. O. L. J . Am. Chem. Soc.
1952, 74, 425-428.

4350 J . Org. Chem., Vol. 61, No. 13, 1996
Nabeshima et al.
The inner aqueous source phase contained metal nitrate (4
mL, see Table 3 and 4 for the concentrations), and the outer
receiving phase consisted of deionized water (40 mL). 1,2-
Dichloroethane (50 mL) containing ionophore (2.0 × 10-4 M)
was used as a liquid membrane. The three phases in the
transport cell were agitated carefully by a stirring bar (200
rpm) on the bottom of the cell at 25 ( 1 °C. The concentrations
of the metal ion in the aqueous receiving phase were deter-
mined by atomic absorption spectroscopy at intervals during
the transport run.
Ack n ow led gm en t. We acknowledge the support of
Fuji Photo Film Co., Ltd. We also thank Associate
Professor Ernst Horn of the University of Tsukuba for
reviewing the English text.
Su p p or tin g In for m a tion Ava ila ble: 13C NMR for com-
pounds 4, 5, 6, 7, 8, 24, 25, 26, 32, and 33, and COSY spectrum
of 2c (13 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of this journal, and may be ordered from the ACS; see
any current masthead page for ordering information.
(44) Lamb, J . D.; Christensen, J . J .; Oscarson, J . L.; Nielsen, B. L.;
Asay, B. W.; Izatt, R. M. J . Am. Chem. Soc. 1980, 102, 6820-6824.
J O9517611