Synthesis and metal transport ability of a new series of thiamacrocycles containing thiol and disulfide groups inside the ring

Article abstract of DOI:10.1002/hc.1044

Synthetic methods for thiamacrocycles containing two thiol groups or a disulfide linkage and their abilities to effect single heavy-metal-ion transport across a liquid membrane were examined. High Ag⁺ selectivity was accomplished by the thiol o

Full text of DOI:10.1002/hc.1044

Heteroatom Chemistry
Volume 12, Number 4, 2001
Synthesis and Metal Transport Ability of a
New Series of Thiamacrocycles Containing
Thiol and Disulfide Groups inside the Ring
Tatsuya Nabeshima,1 Taizo Aoki,2 Tsutomu Haruyama,2
Toshinobu Shinnai,2 Hideaki Ohshiro,2 Toshiyuki Saiki,1
and Yumihiko Yano2
1Department of Chemistry, University of Tsukuba, Tsukuba, Ibaraki 305-8571, Japan
2Department of Chemistry, Gunma University, Kiryu, Gunma 376-8515, Japan
Received 15 December 2000; revised 12 February 2001
reduced form, namely the open state, binds to and
ABSTRACT: Synthetic methods for thiamacrocycles
containing two thiol groups or a disulfide linkage and
ם
transports Ag very selectively. In contrast, the oxi-
ם
dized form shows no affinity for Ag . Generally, the
their abilities to effect single heavy-metal-ion transport
replacement of oxygen atoms of crown ethers by sul-
fur atoms drastically affects the binding strength and
selectivity [3–7]. Thus, the concept of the redox gate
may be extended to the regulation of heavy metal
ions by the use of thiamacrocycles. We report here
the synthesis and metal-transport abilities of the
novel thiamacrocycles 2–4 that possess thiol groups
and a disulfide linkage.
ם
across a liquid membrane were examined. High Ag
selectivity was accomplished by the thiol or disulfide
hosts, although all the corresponding crown ether an-
ם
alogs bearing a disulfide group showed no Ag selec-
tivity. The difference of the transport preferences
among the thiacrown ethers prepared here is consid-
ered to be reflected by the position and the number of
ם
the sulfur atoms ligating to Ag and the cavity size of
the hosts. ᭧ 2001 John Wiley & Sons, Inc. Hetero-
atom Chem 12:276–281, 2001
Incorporation of a gate into a recognition site of a
host is an extremely effective way to control the
binding affinity toward a specific guest [1]. The open
state recognizes the guest via the cavity of the host,
while the closed state does not. Consequently, an all-
or-none type of switching can be achieved if the gate
is respondent to a certain external stimulus. We have
designed macrocycles 1 containing thiol groups and
a disulfide linkage inside the cavity to prove that the
gating concept is useful for ion recognition [1,2]. The
᭧ 2001 John Wiley & Sons, Inc.
276

Synthesis and Metal Transport Ability of a New Series of Thiamacrocycles 277
All the thiamacrocycles were prepared from the tri-
the receiving phase were determined by atomic ab-
sorption spectroscopy. The transport values after 24
hours are summarized in Table 1. All the hosts be-
bromide 5 [8,9] (Scheme 1–3). Treatment of 5 with
Na and ethylene glycol afforded the diol 6. The di-
tosylate 7 obtained from 6 reacted with 5 under high
dilution conditions to give the cyclic dibromide 8.
The dithiol host 2a was obtained by lithiation of 8,
followed by the reaction with elemental sulfur. Oxi-
dation of 2a with hydrogen peroxide in the presence
of K2CO3 produced the disulfide 2b. In the prepara-
tion of the hosts 3 and 4, one hydroxy group of thia-
ethylene glycol oligomers 9 and 14 was protected as
a THP ether and then used for the reaction with 5.
The compounds 11 and 16 thus obtained were de-
protected under acidic conditions to give the diols
12 and 17. Cyclization of 5 with 12 yielded the di-
bromide 13. In a similar fashion, the macrocyclic
dibromide 19 was synthesized (method A), whereas
the cyclization of the ditosylate 18 using Na2S re-
sulted in a low yield of 19 due to the formation of
the cyclic monobromide 20. The bromides 13 and 19
were converted to the hosts 3a and 4a according to
a procedure similar to the preparation of 2a. The di-
thiols 3a and 4a were oxidized by hydrogen peroxide
to give the disulfide hosts 3b (70%) and 4b (92%),
respectively.
ם
sides 2b exhibit effective and selective Ag transport.
ם
In the hosts 2, the thiol form carries Ag more pref-
erentially than the corresponding disulfide 2b, as
seen for 1 [1]. Thiol-containing crown ethers are re-
ם
ported to show a high Ag selectivity, while the trans-
port ability is extremely decreased in the corre-
sponding disulfide containing hosts [1,11]. In
contrast to the thiamacrocycles 2, the disulfide hosts
ם
3b and 4b transport Ag more effectively than the
dithiol hosts 3a and 4a. This tendency, opposite to
that observed in 1 and 2, is probably due to the fact
that the cavities of 3b and 4b are sufficiently large
ם
and preorganized to bind Ag . The cavities of 3a and
4a seem to be too large for effective coordination to
ם
ם
Ag . Compared to 3a and 3b, rates of Ag transport
by 4a and 4b are lower, respectively. However, the
degree of the selectivity enhancement in 4 is larger
than in 3. The difference of the binding preferences
among the crown ethers 1 and the thiacrown ether
derivatives 2–4 is probably reflected by the position
and the number of the sulfur atoms ligating to
ם
Ag and the cavity size of the hosts. We are now pre-
paring crystals of the complexes to clarify the inter-
ם
actions between the hosts and Ag by X-ray
crystallography.
The metal-transport ability of the novel hosts 2–4
were examined by single-ion transport experiments
using a dual cylindrical apparatus [10]. The 1,2-dich-
loroethane layer used as a liquid membrane contains
one of the hosts (2 ן 10מ4 M). A solution of a metal
nitrate (0.01 M) and deionized water were employed
for the source and receiving phases, respectively.
Concentrations of the metal ions transported into
EXPERIMENTAL
For the general methods, see Ref. [6]. Coupling con-
stants (J) are reported in Hz.
Compound 6. Tribromide 5 was added to a so-
lution prepared by dissolution of Na (5.745 g, 0.2499
mmol) in diethlylene glycol (70 g) at room tempera-
ture. The mixture was then stirred at 60ꢀC for 2 days.
The mixture was treated with 3 N HCl (100 mL) and
extracted with CHCl3 (70 mL ן 3). The extracts were
washed with H2O (100 mL ן 2) and saturated aque-
ous NaCl (100 mL), dried over anhydrous MgSO4,
and concentrated under reduced pressure. The resi-
due thus obtained was purified by column chroma-
tography (SiO2, AcOEt-MeOH, 5:2) to give 6 (3.51 g,
1
79%) as a colorless oil. H NMR (200 MHz, CDCl3):
d 2.05 (t, J ס 5.9 Hz), 3.68–3.86 (m, 8H), 4.66 (s, 4H),
7.30–7.45 (m, 3H). 13C NMR (100 MHz, CDCl3): d
61.8, 71.9, 72.8, 123.4, 127.3, 128.5, 137.8. IR (NaCl)
3400 (br), 2870, 1429, 1352, 1130, 1071 cmמ1. MS
ם
SCHEME 1 (a) Na, ethylene glycol, 60ꢀC, 2 days, 79%; (b)
TsCl, NaOH, THF/H2O, מ10ꢀC, 82%; (c) Na2S•9H2O, THF/
EtOH, reflux, 2 days, 29%; (d) BuLi, THF, מ78ꢀC; (e) S8,
מ78ꢀC ꢁ rt; (f) HCl, 48%; (g) H2O2, K2CO3, CH2Cl2/H2O, rt,
73%.
(EI) m/z 304 (M ), 306 (M ם 2).
Compound 7. A solution of TsCl in tetrahydro-
furan (THF) (40 mL) was added dropwise at מ10ꢀC
to a mixture of the diol 6 in THF (40 mL) and NaOH

278 Nabeshima et al.
SCHEME 2 (a) 3,4-dihydro-2H-pyran, TsOH, CH2Cl2/THF, 0ꢀC, 4 hours, 67%; (b) 10, NaH, THF, reflux, 20 hours, 70%; (c) 3
N HCl, MeOH/THF/CHCl3, rt, 39 hours, 74%; (d) 5, NaH, THF, reflux, 5 days, 29%; (e) BuLi, THF, מ78ꢀC; (f) S8, מ78ꢀC ꢁ rt.
(g) HCl, 36%; (h) H2O2, K2CO3, CH2Cl2/H2O, rt, 70%.
SCHEME 3 (a) 3,4-dihydro-2H-pyran, TsOH, CH2Cl2, מ10ꢀC, 2.5 hours, 38%; (b) 15, NaH, THF, reflux, 2 days, 55%; (c) 3
N HCl, MeOH/THF, rt, 34 hours, 85%; (d) 5, NaH, THF, reflux, 4 days, 35%; (e) Na2S•9H2O, THF/EtOH, reflux 1 day, 8%; (f)
BuLi, THF, מ78ꢀC; (g) S8, מ78ꢀC ꢁ rt; (h) HCl, 27%; (i) H2O2, K2CO3, CH2Cl2/H2O, rt, 92%.
in H2O (40 mL). The reaction mixture was poured
into ice water (100 mL), extracted with CH2Cl2 (50
mL), and dried over anhydrous MgSO4. The residue
obtained after evaporation of the solvent was puri-
fied by column chromatography (S:O2, CHCl3–
AcOEt, 10:1) to give 7 (16.9 g, 82%) as a colorless oil:
Compound 8. A solution of 7 (5.544 g, 9.036
mmol) in 50 mL of THF and 50 mL of EtOH was
added dropwise over a period of 3 hours, under re-
flux, to a solution of Na2S•9H2O (2.278 g, 9.458
mmol) in 580 mL of EtOH. After the addition, the
mixture was refluxed for 2 days. The solvent was re-
moved in vacuo, and the residue was mixed with 200
mL of CH2Cl2 and 150 mL of H2O. The organic layer
was washed with 100 mL of H2O and 100 mL of
brine, dried over anhydrous MgSO4, and then con-
centrated in vacuo. The crude product was purified
by silica gel column chromatography using CH2Cl2/
AcOEt (50:1) as an eluent to give 8 (0.795 g, 29%) as
a white powder: m.p. 100–102ꢀC. 1H NMR (200 MHz,
CDCl3): d 2.83 (t, J ס 6.5 Hz, 8H), 3.73 (t, J ס 6.6 Hz,
8H), 4.51 (s, 8H), 7.11–7.36 (m, 6H). 13C NMR (50
1
m.p. 74–75ꢀC. H NMR (200 MHz, CDCl3): d 2.44 (s,
6H), 3.76 (t, J ס 4.8 Hz, 4H), 4.25 (t, J ס 4.6 Hz, 4H),
4.54 (s, 4H), 7.27–7.34 (m, 7H), 7.80 (d, J ס 8.3 Hz,
4H). 13C NMR (50 MHz, CDCl3): d 21.58, 68.24, 69.31,
72.65, 122.68, 127.45, 128.18, 128.25, 130.11, 133.20,
137.63, 145.19. IR (NaCl) 2874, 1734, 1599, 1357,
1170, 1140, 1021, 922 cmמ1. fast atom bombardment
ם
mass spectrometry (FABMS) m/z 613 ([M ם H] ).
Anal. Calcd for C26H29BrO8S2: C, 50.90; H, 4.76.
Found: C, 50.80; H, 4.65.

Synthesis and Metal Transport Ability of a New Series of Thiamacrocycles 279
1201, 1120, 1081, 1027 cmמ1. FABMS m/z 713 ([M ם
TABLE 1 Single Ion Transport for Heavy Metal
ם
H] ).
Conc. of Metal Ion in the Receiving Phase
Compound 12. The bromide 11 (7.232 g, 10.13
(ן 10מ5 M)a
mmol) was treated with a mixture of 30 mL of
ם
Host Ag
Mn2ם Co2ם Ni2ם Cu2ם Zn2ם Cd2ם Pb2ם
MeOH, 40 mL of THF, 10 mL of CHCl3, and 12 mL
of 3N HCl at room temperature for 39 hours. After
evaporation of the solvent and addition of 50 mL of
a 5% NaOH aqueous solution, the mixture was ex-
tracted with CHCl3 (50 mL ן 3). The organic layer
was dried over anhydrous MgSO4 and concentrated
in vacuo. The residue thus obtained was purified by
silica gel column chromatography using CHCl3-
AcOEt (2:1) as an eluent to give 12 (4.110 g, 74%) as
a white solid. 1H NMR (200 MHz, CDCl3): d 2.20 (br,
2H), 2.70–2.85 (m, 16H), 3.67–3.79 (m, 8H), 4.63 (s,
4H), 7.27–7.46 (m, 3H). 13C NMR (100 MHz, CDCl3):
d 31.7, 31.8, 32.8, 35.3, 60.6, 70.8, 72.6, 123.0, 127.3,
128.2, 137.8. IR (NaCl) 3400(br), 2920, 2868, 1427,
1354, 1292, 1203, 1116, 1025 cmמ1. FAB MS m/z 545
2a
2b
3a
3b
4a
4b
6–9b
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0.3
0
0
0
0.1
0
0
0
0
0
0
0
0
0
0
0
0
0
0.6
13.6b
25.6b
4.2
18.1
aThe values were determined after 24 hours [Host] ס 2 ן 10מ4 M in
the liquid membrane, [metal nitrate] ס 0.01 M in the source phase.
bPrecipitates were observed.
MHz, CDCl3): d 32.08, 71.37, 72.65, 123.61, 127.49,
128.71, 138.19. (FABMS) m/z 605 ([M ם H] ). Anal.
Calcd for C24H30Br2O4S2: C, 47.54; H, 4.99. Found: C,
47.36; H, 4.87.
ם
ם
([MםH] ).
Compound 10. 3,4-Dihydro-2H-pyran (2.8 g, 33
mmol) was added slowly at 0ꢀC to a mixture of the
diol 9 (17.5 g, 96.0 mmol) and p-TsOH•H2O (0.647
g, 3.4 mmol) in 150 mL of CH2Cl2: After the mixture
had been stirred for 4 hours, resultant precipitates
were filtered off and then the solvent was removed
in vacuo to give crude 10 (5.876 g) as a colorless vis-
cous oil. The crude product was used without further
purification because a small amount of the corre-
sponding dipyranyl polyether as a by-product was
included. 1H NMR (200 MHz, CDCl3): d 1.49–1.82 (m,
6H), 2.24 (br, 1H, OH), 2.74–2.83 (m, 8H), 3.49–3.98
(m, 6H), 4.62–4.65 (m, 1H). 13C NMR (100 MHz,
CDCl3): d 19.5, 25.4, 30.6, 31.8, 32.0, 32.6, 35.4, 60.7,
62.3, 67.4, 98.9. IR (NaCl) 3300(br), 2924, 1425,
Compound 13. A mixture of 3 (2.578 g, 7.518
mmol) and 12 (4.102 g, 7.518 mmol) in 75 mL of
THF was added dropwise over 24 hours under reflux
to a suspension of 60% NaH (1.541 g, 38.52 mmol)
in 250 mL of THF. After an additional 2 hours of
reflux, a small amount of H2O was added to the mix-
ture to decompose an excess amount of NaH. The
solvent was removed in vacuo, and the residue was
mixed with 50 mL of CHCl3 and 50 mL of H2O. The
aqueous layer was separated and extracted with
CHCl3 (50 mL ן 2). The organic layers were com-
bined, dried over anhydrous MgSO4, and then con-
centrated in vacuo. The crude product thus obtained
was purified by silica gel column chromatography
CHCl3–AcOEt–n-hexane (8:1:8, v/v) to give 13 (1.585
ם
1348, 1203, 1140, 1030 cmמ1; MS (EI) m/z 266 (M ).
1
g, 29%) as a white solid: m.p. 118–119ꢀC. H NMR
Compound 11. A solution of the tribromide 5
(4.980 g, 14.52 mmol) in 100 mL of THF was added
in several portions under reflux to a suspension of
60% NaH (1.526 g, 38.15 mmol) in 65 mL of THF.
After additional reflux for 20 hours, 5 mL of H2O was
added to decompose an excess amount of NaH. The
solvent was evaporated under reduced pressure. The
residue was mixed with CHCl3 and H2O. The organic
layer was dried over anhydrous MgSO4 and concen-
trated in vacuo. The residue thus obtained was pu-
rified by silica gel column chromatography using
CHCl3–AcOEt (20:1) to give 11 (7.255 g, 70%) as a
(200 MHz, CDCl3): d 2.76 (t, J ס 6.2 Hz, 8H), 2.83 (s,
8H), 3.72 (t, J ס 6.3 Hz, 8H), 4.57 (s, 8H), 7.24–7.41
(m, 6H). 13C NMR (125 MHz, CDCl3): d 31.62, 32.79,
71.30, 72.56, 122.78, 127.32, 128.01, 137.81. IR
(KBr) 2914, 2892, 2860, 1474, 1420, 1400, 1356,
מ1
1349, 1281, 1118, 1087, 1039, 1025, 1014, 770 cm
.
ם
FAB MS m/z 725 ([MםH] ). Anal. Calcd for
C28H38Br2O4S4: C, 46.28; H, 5.27. Found: C, 46.17; H,
5.24.
Compound 15. According to a procedure similar
to that used for 10, the alcohol 15 was obtained in
38% yield as a pale yellow oil from 14 (37.989 g,
0.1806 mmol), and p-TsOH•H2O (3.814 g, 20.05
mmol) in CH2Cl2 (200 mL). The crude 15 was puri-
fied by silica gel column chromatography using
CHCl3–AcOEt (5:1), AcOEt-hexane-EtOH (10:8:1),
1
pale orange oil. H NMR (200 MHz, CDCl3): d 1.50–
1.84 (m, 12H), 2.73–2.85 (m, 16H), 3.46–3.97 (m,
12H), 4.63 (s, 6H), 7.27–7.46 (m, 3H). 13C NMR (67.8
MHz, CDCl3): d 19.4, 25.4, 30.6, 31.72, 31.82, 32.67,
32.72, 62.3, 67.5, 70.7, 72.6, 98.9, 122.7, 127.3, 128.0,
137.8. IR (NaCl) 2924, 2868, 1734, 1688, 1427, 1352,
1
and then AcOEt–MeOH (10:1). H NMR (200 MHz,
CDCl3): d 1.49–1.90 (m, 6H), 2.78 (t, J ס 6.7 Hz, 2H),

280 Nabeshima et al.
2.79 (t, J ס 6.4 Hz, 2H,), 2.92 (t, J ס 6.3 Hz, 1H),
3.46–3.93 (m, 14H), 4.62–4.66 (m, 1H). 13C NMR
(67.8 MHz, CDCl3): d 19.5, 25.4 30.6, 31.8, 32.1, 61.8,
62.3, 66.7, 70.3, 70.8, 71.2, 72.1, 99.0. IR (NaCl) 3500
concentrated in vacuo. The crude product was pu-
rified by silica gel column chromatography using
CHCl3–AcOEt (5:1) as an eluent to give 19 as white
needles: m.p. 74–75ꢀC. 1H NMR (200 MHz, CDCl3): d
2.79 (t, J ס 6.6 Hz, 8H), 3.66–3.73 (m, 24H), 4.62 (s,
8H), 7.26–7.43 (m, 6H). 13C NMR (50 MHz, CDCl3):
32.29, 70.72, 70.84, 72.03, 73.19, 123.23, 127.85,
128.53, 138.55. IR (KBr) 2936, 2919, 2895, 2872,
1142, 1120, 1100, 1063, 1041 cmמ1. FABMS m/z 781
(br), 2926, 2870, 1354, 1261, 1203, 1123, 1077, 1036
מ1
cm
.
Compound 16. According to a procedure similar
to that used for 11, 16 was prepared in 55% yield as
a pale yellow oil from 60% NaH (2.000 g, 50.00
mmol), 5 (6.779 g, 19.77 mmol), and 15 (11.644 g,
39.550 mmol) in THF. Purification of 16 was carried
out by silica gel column chromatography using
CHCl3–AcOEt (4:1) as an eluent. 1H NMR (200 MHz,
CDCl3): d 1.47–1.81 (m, 12H), 2.73–2.82 (m, 8H),
3.47–3.89 (m, 28H), 4.65 (s, 6H), 7.27–7.45 (m, 3H).
13C NMR (67.8 MHz, CDCl3): d 19.5, 25.4, 30.6, 31.9,
62.3, 66.6, 70.2, 70.3, 71.1, 71.2, 72.8, 99.0, 122.7,
127.2, 128.0, 137.9. IR (NaCl) 2928, 2870, 1123,
ם
([MםH] ). Anal. Calcd for C32H46Br2O8S2: C, 49.11;
H, 5.92. Found: C, 49.32; H, 5.97.
General Experimental Procedure for the
Synthesis of 2a, 3a, and 4a
A n-BuLi hexane solution (1.64 M, 3.67 mmol) was
added slowly to a stirred solution of bromide 8 (1.67
mmol) in THF (40 mL) at מ78ꢀC. After the mixture
had been stirred for 1 hour at מ78ꢀC, S8 powder was
added. The temperature of the reaction mixture was
raised very slowly to 0ꢀC, and then acidified with di-
lute HCl. The solvent was removed under reduced
pressure. The residue thus obtained was mixed with
CH2Cl2 and washed with H2O and aqueous NaOH.
The organic layer was dried over MgSO4. After the
solvent had been evaporated, the crude product was
purified by recrystallization from AcOEt to give 2a
as pale yellow crystals (0.807 mmol).
ם
1077, 1036 cmמ1. FAB MS m/z 769 ([MםH] ).
Compound 17. According to a procedure similar
to that used for 12, 16 (8.291 g, 10.77 mmol) was
deprotected by the reaction with 3 N HCl (69 mL)
for 34 hours at room temperature in MeOH (30 mL)
and THF (30 mL) to give 17 (5.505 g, 85%) as a pale
yellow oil, after silica gel chromatography using
AcOEt–hexane–EtOH (10:8:1) as an eluent. 1H NMR
(200 MHz, CDCl3): d 2.26 (br, 2H), 2.79 (t, J ס 6.5
Hz, 8H), 3.55–3.74 (m, 24H), 4.66 (s, 4H), 7.27–7.47
(m, 3H). 13C NMR (50 MHz, CDCl3): d 31.95, 32.21,
61.90, 70.37, 70.56, 70.94, 71.45, 72.28, 72.99,
123.14, 127.58, 128.38, 138.30. IR (neat) 3450 (OH),
2868, 2362, 1577, 1352, 1291, 1119, 888, 788, 468
1
Compound 2a. m.p. 137–140ꢀC. H NMR (200
MHz, CDCl3): d 2.81 (t, J ס 6.5 Hz, 8H), 3.70 (t, J ס
6.6 Hz, 8H), 4.56 (s, 8H), 4.57 (s, 2H), 7.07–7.27 (m,
6H). 13C NMR (50 MHz, CDCl3): d 31.98, 70.27, 72.82,
125.53, 130.00, 133.68, 137.31. IR (KBr) 2885, 2862,
2796, 2540 (SH), 1476, 1432, 1355, 1280, 1127, 1089,
1054, 1043, 1034, 1007, 782, 768, 726 cmמ1. Anal.
Calcd for C24H32O4S4: C, 56.22; H, 6.29. Found: C,
55.95; H, 6.09.
ם
cmמ1. FAB MS m/z 601 ([MםH] ).
Compound 18. According to a procedure similar
to that used for 7, 18 was obtained as a colorless oil
in 91% after being purified by column chromatog-
raphy (SiO2, AcOEt–n-hexane–ethanol, 5:4:1, v/v): 1H
NMR (200 MHz, CDCl3): d 2.50 (br. t, 2H), 3.60–3.75
(m, 16H), 4.66 (s, 4H), 7.27–7.45 (m, 3H); 13C NMR
(100 MHz, CDCl3): d 21.6, 68.7, 69.3, 70.1, 70.7, 72.8,
122.8, 127.3, 127.97, 128.04, 129.8, 132.9, 137.8,
144.8. IR (NaCl) 2874, 1599, 1454, 1357, 1178, 1098,
1
Compound 3a. m.p. 107–108ꢀC. H NMR (200
MHz, CDCl3): d 2.71 (t, J ס 6.3 Hz, 8H), 2.76 (s, 8H),
3.65 (t, J ס 6.3 Hz, 8H), 4.53 (s, 2H), 4.59 (s, 8H),
7.12–7.31 (m, 6H). 13C NMR (50 MHz, CDCl3): d
31.78, 32.80, 70.46, 72.66, 125.65, 129.83, 132.88,
137.26; IR (KBr) 2931, 2862, 2843, 2553 (SH), 1446,
1430, 1418, 1400, 1364, 1201, 1091, 1054, 1038,
1026, 1002, 980, 788, 738, 704 cmמ1. Anal. Calcd for
C28H40O4S6: C, 53.13; H, 6.37. Found: C, 53.09; H,
6.42.
Compound 4a. m.p. 67–68ꢀC. 1H NMR (200 MHz,
CDCl3): d 2.77 (t, J ס 6.7 Hz, 8H), 3.62–3.69 (m, 24H),
4.62 (s, 10H), 7.08–7.30 (m, 6H). 13C NMR (50 MHz,
CDCl3): d 32.02, 69.78, 70.43, 71.58, 72.88, 125.49,
129.71, 133.03, 137.30. IR (KBr) 2906, 2868, 2517
(SH), 1115, 1024, 972, 939, 878, 784, 731 cmמ1. Anal.
ם
1019, 922 cmמ1; FABMS m/z 701 ([MםH] ).
Compound 19. (Method A) According to a pro-
cedure similar to that used for 13, 19 was obtained.
A solution of 5 (3.053 g, 8.905 mmol) and 17 (5.358
g, 8.906 mmol) in 50 mL of THF was added slowly
during 1 day under reflux to a suspension of 60%
NaH (0.897 g, 22.4 mmol) in 250 mL of THF. After
an additional 3 day of reflux, decomposition of an
excess NaH with 10 mL of H2O, and evaporation of
the solvent, the residue was mixed with 50 mL of
H2O and then extracted with CHCl3 (50 mL ן 2). The
organic layer was dried over anhydrous MgSO4 and

Synthesis and Metal Transport Ability of a New Series of Thiamacrocycles 281
Calcd for C32H48O8S4: C, 55.79; H, 7.02. Found: C,
55.63; H, 7.02.
128.02, 128.11, 132.13, 140.89. IR (KBr) 2857, 1459,
1442, 1407, 1388, 1368, 1340, 1318, 1293, 1247,
1230, 1130, 984, 909, 884, 786, 669, 542 cmמ1. FAB
ם
MS m/z 687 ([MםH] ).
General Experimental Procedure for the
Synthesis of 2b, 3b, and 4b
REFERENCES
A solution of 2a (0.268 mmol) in CH2Cl2 (50 mL) was
stirred vigorously with 7% aqueous H2O2 (32 mL)
and K2CO3 (2.53 mmol). Subsequently, a saturated
aqueous NaCl solution (20 mL) was added, and the
mixture was extracted with CH2Cl2 (3 ן 30 mL). The
combined organic layers were washed with H2O (2
ן 50 mL) saturated NaCl (50 mL). After evaporation
of the solvent, the residue thus obtained was washed
with AcOEt and H2O to give 2b (0.2 mmol), which
was practically pure as seen from the 1H NMR spec-
trum. Very pure 2b was obtained by recrystallization
from CH2Cl2–AcOEt.
[1] (a) Nabeshima, T.; Furusawa, H.; Yano, Y. Angew
Chem Int Ed Engl 1994, 33, 1750–1751; (b) Arad-Yel-
lin, R.; Green, B. S. Nature 1994, 371, 320–322.
[2] (a) For other metal-binding systems regulated by the
redox reactions between thiols and disulfides, see Ra-
ban, M.; Greenblatt, J.; Kandil, F. J Chem Soc Chem
Commun 1983, 1409–1411; (b) Shinkai, S.; Inuzuka,
K.; Miyazaki, O.; Manabe, O. J Am Chem Soc 1985,
107, 3950–3955; (c) Nabeshima, T.; Sakiyama, A.; Ya-
gyu, A.; Furukawa, N. Tetrahedron Lett 1989, 30,
5287–5288; (d) Graubaum, H.; Tittelbach, F.; Lutze,
G.; Gloe, K.; Mackrodt, M.; Kru¨ger, T.; Krauss, N.;
Deege, A.; Hinrichs, H. Angew Chem Int Ed Engl
1997, 36, 1648–1650.
[3] Izatt, R. M.; Bradshaw, J. S.; Nielsen, S. A.; Lamb,
J. D.; Christensen, J. J. Chem Rev 1985, 85, 271–339.
[4] Izatt, R. M.; Pawlak, K.; Bradshaw, J. S. Chem Rev
1991, 91, 1721–2085.
[5] Nabeshima, T.; Nishijima, K.; Tsukada, N.; Furusawa,
H.; Hosoya, T.; Yano, Y. J Chem Soc Chem Commun
1992, 1092–1094.
1
Compound 2b. m.p. 199–200ꢀC. H NMR (200
MHz, CDCl3): d 2.84 (t, J ס 6.0 Hz, 8H), 3.77 (t, J ס
6.1 Hz, 8H), 4.36 (br, 8H), 7.39 (s, 6H). 13C NMR (125
MHz, CDCl3): d 32.38, 71.53, 71.60, 129.95, 130.61,
136.03, 142.72. IR (KBr) 2910, 2868, 2828, 1349,
מ1
1282, 1172, 1102, 1084, 1047, 1006, 803 cm
.
[6] Nabeshima, T.; Tsukada, N.; Nishijima, K.; Ohshiro,
H.; Yano, Y. J Org Chem 1996, 61, 4342–4350.
[7] (a) Oue, M.; Kimura, K.; Shono, T. Anal Chim Acta
1987, 194, 293–298; (b) Oue, M.; Kimura, K.; Akama,
K.; Tanaka, M.; Shono, T. Chem Lett 1988, 409–410;
(c) Oue, M.; Akama, K.; Kimura, K.; Tanaka, M.;
Shono, T. J Chem Soc Perkin Trans 1 1989, 1675–
1678.
HRMS calcd for C24H30O4S4 m/z 510.1027. Found m/
z 510.0992.
Compound 3b. m.p. 162–163ꢀC (from AcOEt-
1
hexane). H NMR (200 MHz, CDCl3): d 2.68 (t, J ס
6.2 Hz, 8H), 2.85 (s, 8H), 3.66 (br, 8H), 4.41 (br, 8H),
7.44 (s, 6H). 13C NMR (50 MHz, CDCl3): d 31.09,
32.88, 70.93, 71.92, 128.38, 130.80, 132.34, 143.43.
[8] Vo¨gtle, F. Chem Ber 1969, 102, 1784–1788.
[9] Newcomb, M.; Moore, S. S.; Cram, D. J. J Am Chem
Soc 1977, 99, 6405–6410.
IR (KBr) 2920, 2863, 1424, 1409, 1352, 1206, 1107,
מ1
1054, 1000, 806, 789 cm
. Anal. Calcd for
C28H38O4S6: C, 53.30; H, 6.07. Found: C, 53.27; H,
6.14.
Compound 4b. 1H NMR (200 MHz, CDCl3): d 2.80
(t, J ס 6.4 Hz, 8H), 3.60 (s, 16H), 3.68 (t, J ס 6.5 Hz,
8H), 4.51 (br, 8H), 7.27–7.46 (m, 6H). 13C NMR (50
MHz, CDCl3): d 32.00, 70.44, 70.80, 71.56, 72.42,
[10] (a) Nabeshima, T.; Inaba, T.; Furukawa, N. Tetrahe-
dron Lett 1987, 28, 6211–6214; (b) Nabeshima, T.; In-
aba, T.; Furukawa, N.; Hosoya, T.; Yano, Y. Inorg
Chem 1993, 32, 1407–1416.
[11] Nabeshima, T.; Furusawa, H.; Tsukada, N.; Shinnai,
T.; Haruyama, T.; Yano, Y. Heterocycles 1995, 41,
655–659.