Syntheses of diazadithiacrown ethers containing appended coumarin or 1-aminonaphthalene sidearms

Article abstract of DOI:10.1002/jhet.5570400311

Six crown ethers containing two coumarin (11, 13, 14, 16, 17 and 19) or two 1-aminonaphthalene (15 and 20) fragments as sidearms and two crown ethers bearing one coumarin (12 and 18) arm were synthesized by a nucleophilic substitution of the secondary macrocyclic amine function on the alkyl halide. The major products of these reactions were the diazadithiacrown ethers containing two sidearms. In some cases, one-armed diazadithiacrown ethers were separated as minor products, although more than 2.5 mmoles of alkyl halide were used for 1.0 mmole of macrocyclic diamine.

Full text of DOI:10.1002/jhet.5570400311

May-Jun 2003
475
Syntheses of Diazadithiacrown Ethers Containing Appended
Coumarin or 1-Aminonaphthalene Sidearms
Hua-Can Song [a], Yi-Wen Chen [b], Jun-Hua Yao [b], Zun-Le Xu [a],
*
Jerald S. Bradshaw [c], Paul B. Savage [c] and Reed M. Izatt [c]
[a] Department of Chemistry, [b] Center of Analysis and Measurement, Zhongshan University, Guangzhou
510275 P. R. China; [c] Department of Chemistry and Biochemistry, Brigham Young University,
Provo, UT 84602 USA
Received January 21, 2003
Six crown ethers containing two coumarin (11, 13, 14, 16, 17 and 19) or two 1-aminonaphthalene (15 and
20) fragments as sidearms and two crown ethers bearing one coumarin (12 and 18) arm were synthesized by
a nucleophilic substitution of the secondary macrocyclic amine function on the alkyl halide. The major
products of these reactions were the diazadithiacrown ethers containing two sidearms. In some cases, one-
armed diazadithiacrown ethers were separated as minor products, although more than 2.5 mmoles of alkyl
halide were used for 1.0 mmole of macrocyclic diamine.
J. Heterocyclic Chem., 40, 475 (2003).
Introduction.
Numerous ion-selective chemo sensors, based on syn-
thetic fluoroionophores, have been reported [4-13]. For
example, Bradshaw and his co-workers found that crown
ethers containing 8-hydroxyquinoline fragments as
sidearms (1-3, Figure 1) are excellent Mg , Ba or Hg
ion-selective chemo sensors [14-16]. It was also reported
The toxicities of many transition and post-transition
metal ions are well recognized [1]. As a result, much
attention has been paid to controlling contamination of
water supplies by toxic metal ions and to monitoring their
levels in the environment [2]. Traditional methods of mea-
suring metal ion concentrations in waste steams are usu-
ally spectroscopic and wet chemical analysis techniques
on samples removed from the waste steams [3]. An attrac-
tive alternative to these methods would be to monitor the
concentrations of specific metal ions in a complex matrix
continuously and remotely by using ion-selective sensory
devices. Ion-selective chemo sensors may play a central
role in developing such devices.
2+
2+
2+
recently that a crown ether bearing a coumarin sidearm (4,
2+
Figure 1) showed an excellent selectivity for Pb [17].
It is well known that the complexing ability and selectiv-
ity of lariat ethers for metal ions can be changed by vary-
ing certain parameters, such as the size of the crown ether
ring and the type, number and position of the ring com-
plexing heteroatoms [10,18-20]. Sulfur atoms have a high
2+
2+
affinity and selectivity for Pb and Hg . Therefore,

476
H.-C. Song, Y.-W. Chen, J.-H. Yao, Z.-L. Xu, J. S. Bradshaw, P. B. Savage and R. M. Izatt
Vol. 40
adding to our previous work [7-9,11,12], we report herein
the synthesis of 10 diazadithiacrown ethers containing 18
and 24 ring members, which bear coumarin or 1-amino-
naphthalene sidearms (11-20, Scheme 2).
desired compounds were difficult to isolate and purify
when acetonitrile was used as the solvent. When methanol
was used, the reaction mixtures were less complex and the
major products were easier to isolate and purify.
Results And Discussion.
Intermediates 21 and 22 (Scheme 3) were prepared in a
straight-forward manner by treating 4-methyl-7-hydroxy-
coumarin with 1.5 eq. of 1,2-dichloroethane or 1,3-dibro-
mopropane in the presence of sodium hydroxide.
Compounds 23 and 24 were synthesized by the reaction of
chloroacetyl chloride with the appropriate aromatic amine
in the presence of sodium acetate. Preparation of 23 and
24 required synthesis of 3-aminocoumarin. After investi-
gating published methods [21-23], we found that if equiv-
alent amounts of salicylaldehyde and methyl aminoacetate
hydrochloride were reacted in water at pH 8-9, 3-
aminocoumarin was formed in 84% yield. In addition, the
desired compound was easily purified by recrystallization
from the reaction residue.
Dichlorodiamide starting materials 5 and 6 were synthe-
sized by the reaction of chloroacetic anhydride or
chloroacetyl chloride with the appropriate diamine
(Scheme 1). Macrocyclic diamides 7 and 8 (58%) were
prepared by treating the appropriate dichlorodiamide with
3-oxa-1,5-pentanedithiol. The cyclic amides were reduced
in good yields using NaBH -BF -(OEt) in THF to form
the corresponding secondary macrocyclic diamines 9
(70%) and 10 (70%) as reported [7-9,11].
The preparation of ligands 11-20 (Scheme 2) was accom-
plished by nucleophilic substitution by the appropriate
macrocyclic secondary amine on the corresponding alkyl
halide where X = bromide or chloride. A solution of the
macrocyclic diamine, the appropriate alkyl halide and tri-
ethylamine in methanol was refluxed for 4 days. The
desired compounds were separated from the reaction mix-
ture by chromatography on a silica gel column. Initially,
2.2 eq. of the corresponding alkyl halide were used. A
small amount of one-armed by-product was isolated in two
instances from these reaction mixtures; however, the yield
of the two-armed product was unsatisfactory. Using 2.5-3.0
eq. of alkyl halide and increasing the reaction time from
one day to four days gave satisfactory yields of the two-
armed product along with a minor amount of the one-armed
by-product. Acetonitrile is usually used in this type of
nucleophilic substitution reaction [7]; however, because the
solubility of many of our starting materials was very low in
acetonitrile, methanol was used as the solvent in this study.
In addition, the product mixtures were complex and the
4
3
2
The structures of all new macrocyclic compounds were
1
13
consistent with data obtained from H and C nmr spec-
tral analyses and ms analyses. In addition, the new macro-
cycles containing sidearms (11-20) exhibited satisfactory
elemental analyses or hrms molecular weights.
EXPERIMENTAL
All starting materials were used as purchased from commercial
sources. Macrocyclic diamine 7 was prepared as reported [8].
7-(2-Chloroethoxy)-4-methylcoumarin (21) (Scheme 3).
4-Methyl-7-hydroxycoumarin (8.80 g, 50.0 mmole) and
sodium hydroxide (2.0 g, 50.0 mmole) were dissolved in 200 mL
of methanol. 1,2-Dichloroethane, (7.92 g, 6.4 mL 80.0 mmole)
was added and the mixture was refluxed for 3 days. The solvent

May-Jun 2003
Syntheses of Diazadithiacrown Ethers
477
1
was evaporated under reduced pressure and the residue was sepa-
rated by silica gel chromatography using chloroform as eluent to
give 8.35 g (70%) of 21, mp 103-104°; H nmr: δ 2.41 (s, 3H),
238-239°; H nmr: δ 4.23 (s, 2H), 7.33-7.35 (m, 1H), 7.36 (d, J =
3.7 Hz, 1H), 7.48 (dd, J = 8.0 Hz, J = 1.5 Hz, 1H), 7.54 (dd, J
= 8.0 Hz, J = 1.5 Hz, 1H), 8.70 (s, 1H), 9.14(s, 1H, NH);
1
2
1
C
1
13
2
3.87 (t, J = 5.6 Hz, 2H), 4.30 (t, J = 5.8 Hz, 2H), 6.16 (s, 1H),
6.82 (d, J = 2.6 Hz, 1H), 6.89 (dd, J = 8.8 Hz, J = 2.4 Hz, 1H),
7.51(d, J = 8.8 Hz, 1H); C nmr: δ 19.1, 42.0, 68.8, 102.1, 112.7,
nmr: δ 43.2, 117.0, 119.8, 123.7, 124.6, 125.7, 128.5, 130.7,
+
150.7, 158.8, 165.7; ms (fab) for C H NO Cl (M+H) , calcd.
1
2
11
9
3
13
238.0, found 238.0.
113.0, 114.6, 126.2, 152.9, 155.6, 161.6; ms (fab) for
1-(Chloromethylformylamino)naphthalene (24) (Scheme 3).
+
C
H
N O Cl (M+H) , calcd. 239.0, found 239.0.
12 12
2 3
Compound 24 (18.4 g, 84%) was prepared as above for 23
7-(3-Bromopropoxy)-4-methylcoumarin (22) (Scheme 3).
from 14.32 g (10.0 mmole) of 1-aminonaphthalene and 11.30 g
1
Compound 22 (2.97 g, 50%) was prepared as above from 3.52
(10.0 mmole, 11.30 g) of chloroacetyl chloride; mp 155-156°; H
g (20.0 mmole) of 4-methyl-7-hydroxycoumarin and 6.46 g (32.0
mmole) of 1,3-dibromopropane; mp 82-83°; H nmr: δ 2.32-2.38
nmr: δ 4.37 (s, 2H), 7.45-7.63 (m, 3H), 7.76 (d, J = 8.3 Hz, 1H),
1
13
7.88-7.93 (m, 2H), 7.99 (d, J = 7.4 Hz, 1H), 8.80 (s, 1H);
C
(m, 2H), 2.40 (s, 3H), 3.61 (t, J = 6.4 Hz, 2H), 4.17 (t, J = 5.7 Hz,
nmr: δ 43.8, 120.6, 121.0, 126.1, 126.7, 126.9, 127.2, 129.3,
+
148.2, 153.2, 165.5; ms (fab) for C H NOCl (M+H) , calcd.
12 11
2H), 6.13 (s, 1H), 6.81 (d, J = 2.5 Hz, 1 H), 6.85 (dd, J = 8.7 Hz,
1
13
J = 2.4 Hz, 1H), 7.48 (d, J = 8.7 Hz, 1H); C nmr: δ 19.1, 30.1,
220.0, found 220.0.
2
32.4, 66.3, 102.0, 112.5, 112.8, 114.2, 126.1, 153.0, 155.6, 161.7,
1,13-Diaza-4,7,10,19-tetraoxa-16,22-dithiacyclotetracosane-
14,24-dione (8) (Scheme 1).
+
162.1; ms (fab) for C
297.0.
H
O Br (M+H) , calcd. 297.0, found
13 14
3
Macrocyclic diamide 8 was prepared as a viscous liquid (7.10
g, 58%) as in reference [8] from 10.32 g (30.0 mmole) of
dichlorodiamide 6 and 4.14 g (30.0 mmole) of 2,2’-oxydi-
3-Aminocoumarin.
Salicylaldehyde (12.2 g, 0.10 mole) and 12.6 g (0.10 mole) of
methyl aminoacetate hydrochloride were mixed and the pH value
of the mixture was adjusted to 8-9 using triethylamine. The
resulting mixture was heated to 80-90° for 30 minutes. The mix-
ture was allowed to cool to room temperature and stirring was
continued until a precipitate formed. The crude product was iso-
lated by filtration and washed with water. The solid was recrys-
tallized from ethanol to give 13.36 g (83%) of a white solid prod-
uct; mp 127-128° [literature 132-133°] [24].
1
ethanethiol; H nmr: δ 2.79 (t, J = 5.9 Hz, 4H), 3.31 (s, 4H), 3.50
(q, J = 5.7 Hz, 4H), 3.58 (t, J = 4.8 Hz, 4H), 3.71-3.62 (m, 12 H),
13
7.48(s, 2H), C nmr: δ 34.2, 38.1, 41.2, 71.4, 72.0, 72.2, 72.3,
+
170.6; ms (fab) for C
H
N O S (M+H) , calcd. 411.2, found
16 31
2 6 2
+
411.2; hrms for C
H N O S (M+H) : calcd. 411.1623, found
16 31 2 6 2
411.1631.
1,7-Diaza-4,13-dioxa-10,16-dithiacyclootadecane (9)
(Scheme 1).
3-(Chloromethylformylamino)coumarin (23) (Scheme 3).
Compound 7 (4.0 g, 12.4 mmole) and 1.51 g (40.0 mmole) of
sodium borohydride were dissolved in 300 mL of dried tetrahy-
drofuran. The mixture was cooled on an ice-bath, 16.1 mL (60.0
mmole) of boron trifluoride etherate was added dropwise at 0-5°
and the mixture was allowed to warm to room temperature. The
mixture was refluxed for 5 days and most of the tetrahydrofuran
was evaporated under reduced pressure. Water (50 mL) was
added to the mixture and the solid salt was filtered. The mixture
was neutralized with 20% aqueous sodium hydroxide to pH = 8.
The tetrahydrofuran in the mixture was removed by evaporation
3-Aminocoumarin (4.83 g, 30.0 mmole) and 4.92 g (45.0
mmole) of anhydrous sodium acetate was dissolved in 100 mL of
dried acetonitrile and the mixture was cooled on an ice-bath.
Chloroacetyl chloride (3.39 g, 30.0 mmole) was added dropwise
to the mixture. The mixture was allowed to warm to room tem-
perature and stirring was continued for 10 minutes. The solvent
was evaporated under reduced pressure and the residue was
washed with water. The desired product was separated by silica
gel chromatography to give 6.40 g (90%) of a white solid; mp

478
H.-C. Song, Y.-W. Chen, J.-H. Yao, Z.-L. Xu, J. S. Bradshaw, P. B. Savage and R. M. Izatt
Vol. 40
in vacuum. The product was extracted with chloroform and the
solvent was evaporated under reduced pressure. The residue was
separated by chromatography on a silica gel column using
nmr: δ 1.95 (t, J = 6.5 Hz, 4H), 2.37 (s, 6H), 2.81-2.63 (m, 24H),
3.65 (t, J = 5.5 Hz, 4H), 4.06 (t, J = 5.9 Hz, 4H), 6.10 (s, 2H),
6.77 (d, J =2.5 Hz, 2H), 6.82 (dd, J = 8.8, J = 2.5 Hz, 2H), 7.46
1
2
13
CHCl :CH OH:NH .H O = 100:5:0.5 as eluent to give 2.56 g
(d, J = 8.8 Hz, 2H); C nmr: δ 20.4, 28.6, 31.7, 34.1, 34.2, 52.8,
3
3
3
2
1
(70%) of viscous liquid 9; H nmr: δ 2.29 (s, 2H), 2.71-2.82 (m,
16H), 3.58 (t, J = 4.8 Hz, 4H), 3.69 (t, J = 5.4 Hz, 4H); C nmr:
55.5, 56.6, 68.0, 71.3, 103.0, 113.5, 114.2, 115.2, 127.2, 154.3,
13
+
156.9, 163.0, 163.7; ms (fab) for C
727.3, found 726.3.
H
N O S (M+H) calcd.
38 51
2
8
2
,
δ 32.1, 33.2, 48.5, 49.1, 70.1, 71.9; hrms for C
(M+H) , calcd. 295.1566, found 295.1515.
H N O S
12 27 2 2 2
+
Anal. Calcd. for C
H N O S : C, 62.78; H, 6.93; N, 3.85.
38 50 2 8 2
Found C, 62.65; H, 6.57; N,3.68.
1,13-Diaza-4,7,10,19-tetraoxa-16-22-dithiacyclotetracosane (10)
(Scheme 1).
1,7-Bis(3-coumarinylaminoformylmethyl)-1,7-diaza-4,13-dioxa-
10,16-dithiacyclooctadecane (14) (Scheme 2).
Macrocyclic diamine 10, (2.69 g, 70%), was prepared as a vis-
cous liquid from 4.10 g (10.0 mmole) of macrocyclic diamide 8 as
above; H nmr: δ 2.80 (t, J = 5.9 Hz, 4H), 3.31 (s, 4H), 3.50 (q,
Ligand 14 (0.15 g, 31%) was obtained from 0.20 g (0.7
mmole) of 9 and 0.50 g (2.1 mmole) of 23, according to the gen-
1
1
J =5.1 Hz, 4H), 3.57-3.61 (m, 4H), 3.63-3.71 (m, 16H), 7.48 (s,
eral procedure; H nmr: δ 2.82 (t, J = 6.5 Hz, 4H), 2.90 (m, 8H),
13
2H); C nmr: δ 34.2, 38.1, 41.2, 71.5, 72.0, 72.2, 72.3, 73.6; ms
3.00 (s, 4H), 3.33 (s, 4H), 3.61 (t, J = 4.5 Hz, 4H), 3.74 (t, J = 6
Hz, 4H), 7.27 (t, J = 7.5 Hz, 2H), 7.29 (d, J = 8.0 Hz, 2H), 7.42 (t,
J = 8.1 Hz, 2H), 7.49 (d, J = 7.5 Hz, 2H), 8.68 (s, 2H), 10.05 (s,
+
(fab) for C H N O S (M+H) , calcd. 383.2, found 383.2; hrms
16 35
2 4 2
+
for C H N O S (M+H) , calcd. 383.2038, found 383.2035.
16 35
2 4 2
13
2H); C nmr δ: 30.0, 31.4, 54.7, 55.8, 59.7, 69.6, 71.9, 116.2,
General Procedure for the Preparation of 11-20 (Scheme 2).
119.8, 123.3, 123.9, 124.9?127.6, 129.5, 150.2, 158.2, 171.2; ms
+
The macrocyclic diamine (2.0 mmole) and 3.0 mmole of the
appropriate alkyl halide were dissolved in 100 mL of methanol
and 6.0 mmole of triethylamine was added. The mixture was
refluxed for 5 days and the solvent was evaporated under reduced
pressure. The residue was chromatographed on silica gel using
(fab) for C
H
N O S (M+H) calcd. 697.2, found 697.2.
34 41
4
8
2
,
Anal. Calcd. for C
H N O S •CH OH: C, 58.13; H, 5.94;
34 40 4 8 2 3
N, 7.86. Found C, 58.16;H, 5.53; N, 7.62.
1,7-Bis(1-naphthylaminoformylmethyl)-1,7-diaza-4,13-dioxa-
10,16-dithiacyclooctadecane (15) (Scheme 2).
CHCl :MeOH:NH .H O = 100:2:0.2 as eluent to obtain the
3
3
2
desired products.
Macrocyclic amine 9 (0.20 g, 0.7 mmole) was treated with 2.1
mmole (0.46 g) of chloroacetamide 24 in methanol to give 15
(0.18 g, 39%) as a viscous yellow liquid; H nmr: δ 2.63 (s, 4H),
1,7-Bis[2-(4-methyl-7-coumarinyl)oxyethyl]-1,7-diaza-4,13-
dioxa-10,16-dithiacyclooctadcane (11) (Scheme 2).
1
2.73 (t, J = 5.6 Hz, 4H), 2.80 (d, J = 4.9 Hz, 4H), 2.84 (d, J = 4.8
Hz, 4H), 3.27 (s, 4H), 3.49 (t J = 5.5 Hz, 4H), 3.67 (t, J = 5.6 Hz,
4H), 7.27-7.55 (m, 6H), 7.67 (d, J = 8.2 Hz, 2H), 7.84 (d, J = 8.2
According to the general procedure, 0.15 g (31%) of 11 was
separated as a yellow viscous liquid from 0.2 g (0.7 mmole) of 9
and 0.50 g (2.1 mmole) of 21; H nmr: δ 2.37 (s, 6H), 2.72-2.81
1
13
Hz, 2H), 8.07 (t, J = 8.2 Hz, 4H), 10.00 (s, 2H); C nmr: δ 31.5,
(m, 8H), 2.85 (t, J = 5.5 Hz, 4H), 2.94 (t, J = 5.7 Hz, 4H), 3.01 (t,
J = 5.7 Hz, 4H), 3.60 (t, J = 5.5 Hz, 4H), 3.67 (t, J= 6.1 Hz, 4H),
4.10 (t, J = 5.7 Hz, 4H), 6.11 (s, 2H), 6.78 (d, J = 2.4 Hz, 2H),
6.85 (dd, J = 8.8 Hz, J = 2.5 Hz, 2H), 7.47 (d, J = 8.8 Hz, 2H);
32.2, 54.7, 55.2, 59.6, 68.8, 71.8, 119.5, 121.4, 125.2, 125.8,
125.9, 126.8, 128.6, 132.6, 134.1, 169.8; ms (fab) for
+
C
H
N O S (M+H) calcd. 661.3, found 661.2.
36 45
4
4
2
,
Anal. Calcd. for C
H
N O S . H O: C, 64.55; H, 6.77; N,
1
2
36 44
4
4
2
2
13
C nmr: δ 20.3, 31.7, 33.2, 55.3, 55.9, 57.1, 68.8, 71.6, 73.5,
8.36. Found C, 64.84; H, 5.87; N,8.06.
103.1, 113.5, 114.1, 115.2, 127.3, 154.3, 156.8, 162.8, 163.4; ms
1,13-Bis[2-(4-methyl-7-coumarinyl)oxyethyl]-1,13-diaza-
4,7,10,19-tetraoxa-16,22-dithiacyclotetracosane (16).
+
(fab) for C
H
N O S (M+H) , calcd. 699.3, found 699.3.
36 47
2 8 2
Anal. Calcd. for C
H N O S : C, 61.87; H, 6.63; N, 4.01.
36 46 2 8 2
Found C, 61.68; H, 6.32; N, 3.92.
According to the general procedure, 0.20 g (0.5 mmole) of
macrocyclic diamine 10 was treated with 1.5 mmole (0.36 g) of
21 to give 0.22 g (56%) of viscous liquid 16; H nmr: δ 2.39 (s,
6H); 2.89 (m, 4H), 2.73-2.79 (m, 8H), 2.95 (t, J = 2.0 Hz, 4H),
3.06 (s, 4H), 3.59-3.67 (m, 16H), 4.1 (t, J = 5.0 Hz, 4H), 6.12 (d,
1-[2-(4-Methyl-7-coumarinyl)oxyethyl]-1,7-diaza-4,13-dioxa-
10,16-dithiacyclooctadecane (12) (Scheme 2).
1
According to the general procedure, compound 15 was isolated
as a minor product from the reaction residue in which ligand 11
J = 1.0 Hz, 2H), 6.81 (d, J = 2.5 Hz, 2H), 6.85-6.87 (dd, J = 8.5
1
1
13
was obtained; H nmr: δ 2.38 (s, 3H), 2.71-2.84 (m, 14H), 2.90 (t,
Hz, J = 2.5 Hz, 2H), 7.48 (d, J = 8.5 Hz, 2H); C nmr: δ 20.3,
2
J = 5.4 Hz, 2H), 2.98 (t, J = 5.5 Hz, 2H), 3.60-3.66 (m, 6H), 3.82
(t, J = 4.4 Hz, 2H), 4.09 (t, J = 5.42 Hz, 2H), 6.11 (s, 1H), 6.81 (d,
J = 2.4 Hz, 1H), 6.86 (dd, J = 8.8 Hz, J = 2.5 Hz, 1H), 7.48 (d,
J = 8.8 Hz, 1H); C nmr: δ 20.4, 31.3, 32.8, 33.2, 34.0, 49.4,
50.0, 54.7, 55.4, 56.1, 67.8, 68.5, 70.5, 72.5, 73.7, 103.4, 113.6,
31.3, 31.5, 33.4, 55.0, 55.8, 57.2, 68.7, 71.3, 72.3, 73.0, 103.2,
113.6, 114.2, 115.3, 127.7, 154.3, 156.8, 162.9, 163.3; ms (fab)
for C
H N O S , calcd. 787.3, found 787.3; hrms for
1
2
40 55 2 10 2
13
+
C
H N O S (M+H) , calcd. 787.3298, found 787.3301.
40 55 2 10 2
1,13-Bis[3-(4-methyl-7-coumarinyl)oxypropyl]-1,13-diaza-
4,7,10,19-tetraoxa-16,22-dithiacyclotetracosane (17).
114.1, 115.4, 127.4,154.4, 156.8, 163.0, 163.3; ms (fab) for
+
C
C
H
N O S (M+H) calcd. 497.2; found 497.2. hrms for
24 37
2
5
2
,
+
H
N O S (M+H) , calcd. 497.2144, found 497.2141.
Ligand 17 (0.22 g, 54%) was obtained as a viscous liquid from
0.20 g (0.5 mmole) of macrocyclic diamine 10 and 0.45 g (1.5
24 37
2 5 2
1,7-Bis[3-(4-methyl-7-coumarinyl)oxypropyl]-1,7-diaza-4,13-
dioxa-10,16-dithiacyclooctadecane (13) (Scheme 2).
1
mmole) of 22, according to the general procedure; H nmr: δ 2.04
(s, 4H), 2.40 (s, 6H), 2.73 (t, J = 6.0 Hz, 4H), 2.75 (m, 4H), 2.81
(t, J = 2.0 Hz, 4H), 2.84 (t, J = 0.9 Hz, 4H), 3.40 (t, J = 1.5 Hz,
4H), 3.58 (t, J = 3.5 Hz, 4H), 3.62 (t, J = 6.0 Hz, 4H), 3.65 (t, J =
Compound 13 (0.22 g, 43%) was obtained as a viscous liquid
1
from 0.20 g (0.7 mmole) of 9 and 0.62 g (2.1 mmole) of 22; H

May-Jun 2003
Syntheses of Diazadithiacrown Ethers
479
6.5 Hz, 4H), 3.68 (t, J = 6.0 Hz, 4H), 4.10 (t, J = 6.0 Hz, 4H),
of National Education for financial support.
REFERENCES AND NOTES
6.12 (d, J = 1.0 Hz, 2H), 6.80 (d, J = 2.5 Hz, 2H), 6.85 (dd, J =
1
13
8.5 Hz, J = 2.5 Hz, 2H), 7.48 (d, J = 9.0 Hz, 2H); C nmr: δ
2
18.6, 26.5, 30.0, 31.9, 46.7, 51.2, 53.2, 54.7, 66.2, 70.5, 71.3,
101.5, 109.0, 112.5, 113.6, 125.5, 152.5, 155.2, 161.2, 161.9; ms
[1] E. Foulkes, Biological Effects of Heavy Metals; CRC
Press, Boca Raton, FL; Vols. 1 and 2 (1990).
+
(fab) for C
H
N O S (M+H) , calcd. 815.4; 815.4; hrms for
42 59
2 10 2
+
C
H N O S (M ), calcd. 814.3533, found: 814.3530
42 58 2 10 2
[2] A. Boudou and F. Ribeyre, In: Sigel, H., ed, Metal Ions in
Biological Systems; Marcel Dekker, New York; Vol. 34 (1997).
[3] J. Lester, Heavy Metals in Wastewater and Sludge
Treatment Processes; CRC Press, Boca Raton, FL; Vols. 1 (1987).
[4] K. Kokubo, H. Kakimoto and T. Oshima, J. Am. Chem.
Soc. 124, 6548 (2002).
1-[3-(4-methyl-7-coumarinyl)oxypropyl]-1,13-diaza-4,7,10,19-
tetraoxa-16,22-dithiacyclotetracosane (18).
One-arm product 18 was isolated as a viscous liquid when lig-
1
and 17 was prepared according to the general procedure; H nmr:
δ 1.94-1.98 (m, 2H), 2.40 (s, 3H), 2.72-2.77 (m, 10H), 2.89 (t, J =
6.0 Hz, 2H), 2.95 (t, J = 9.0 Hz, 2H), 3.46-3.73 (m, 20H), 4.11 (t,
J = 6.0 Hz, 2H), 6.12 (s, 1H), 6.83 (d, J = 2.0 Hz, 1H), 6.88 (t, J =
8.5 Hz, 1H), 7.49 (d, J = 8.5 Hz, 1H); C nmr: δ 18.6, 26.6, 29.6,
30.0, 32.0, 32.2, 47.7, 47.8, 51.1, 53.5, 54.8, 62.5, 66.5, 68.9,
70.1, 70.2, 70.6, 70.9, 71.2, 71.8, 101.5, 111.8, 112.5, 113.5,
[5] N. Su, J. S. Bradshaw, X. X. Zhang, P. B. Savage, K. E.
Krakowiak and R. M. Izatt., J. Org. Chem., 64, 3825 (1999).
[6] K. Rurack, M. Kollmannsberger, U. Resch-Genger and J.
Daub, J. Am. Chem. Soc., 122, 968 (2000).
[7] H.-C. Song, J. S. Bradshaw, Y.-W. Chen, G.-P. Xue, W.-M.
Li, K. E. Krakowiak, P. B. Savage, Z.-L. Xu and R. M. Izatt,
Supramol. Chem., 14, 263 (2002).
[8] J. S. Bradshaw, H.-C. Song, G.-P. Xue, R. T. Bronson, J.
A. Chiara, K. E. Krakowiak, P. B. Savage and R. M. Izatt, Supramol.
Chem., 13, 499 (2001).
13
125.5, 152.5, 155.2, 161.2, 162.0; hrms (fab) for C
(M+H) , calcd. 599.2824, found, 599.2819.
H N O S
29 47 2 7 2
+
1,13-Bis-(3-comarinylaminoformylmethyl)-1,13-diaza-
[9] H.-C. Song, J. S. Bradshaw, Y.-W. Chen, G.-P. Xue, W.-M.
Li, K. E. Krakowiak, P. B. Savage, Z.-L. Xu and R. M. Izatt,
ARKIVOC, ISSUE in Honor of Prof. Miha Tisler, 2, Part 3, ms 0116
(2001).
[10] R. M. Izatt, K. Pawlak, J. S. Bradshaw and R. L. Bruening,
Chem. Rev., 95, 1231 (1995).
[11] H.-C. Song, Y.-W. Chen, J.-G. Song, P. B. Savage, G.-P.
Xue, J. A. Chiara, K. E. Krakowiak, R. M. Izatt and J. S. Bradshaw,
J. Heterocyclic Chem., 38, 1369 (2001).
4,7,10,19-tetraoxa-16,22-dithiacyclotetracosane(19).
According to the general procedure, 0.20 g (0.5 mmole) of
diamine 10 reacted with 1.5 mmole (0.36 g) of 23 to give 0.20 g
1
(51%) of viscous liquid ligand 19; H nmr: δ 2.77-2.92 (m, 16H),
3.42 (m, 4H), 3.67-3.79 (m, 16H), 7.25-7.29 (m, 4H), 7.37 (d, J =
1.4 Hz, 2H), 7.42 (dd, J = 8.6 Hz, J = 1.4 Hz, 2H), 8.68 (d, J =
1
2
13
5.4 Hz, 2H), 10.03 (s, 2H); C nmr: δ 29.6, 29.9, 31.6, 54.5,
55.7, 59.6, 69.5, 70.5, 71.4, 116.2, 119.8, 123.3, 123.9, 124.9,
[12] G.-P. Xue, J. S. Bradshaw, H.-C. Song, R. T. Bronson, P.
B. Savage, K. E. Krakowiak and R. M. Izatt, Tetrahedron, 57, 87
(2001).
[13] Z.-H. Yang, J. S. Bradshaw, X. X. Zhang, P. B. Savage, K.
E. Krakowiak, N. K. Dalley, N. Su, R. T. Bronson and R. M. Izatt., J.
Org. Chem., 64, 3162 (1999).
127.6, 129.4, 150.1, 158.1, 171.2; ms (fab) for C
H
N O
S
S
38 49
4
10
10
2
2
+
(M+H) , calcd. 785.3, found 785.3; hrms for C
(M+H) , calcd. 785.2890, found, 785.2896.
H N O
38 49 4
+
Anal. Calcd. for C
H N O S : C, 58.15; H, 6.16. Found C,
38 48 4 10 2
57.82; H, 5.87.
[14] X. X. Zhang, A. V. Bordunov, J. S. Bradshaw, N. K.
Dalley, X. Kou and R. M. Izatt, J. Am. Chem. Soc., 117, 11507
(1995).
[15] L. Prodi, C. Bargossi, M. Montalti, N. Zaccheroni, N. Su,
J. S. Bradshaw, R. M. Izatt and P. B. Savage, J. Am. Chem. Soc., 122,
6769 (2000).
1,13-Bis-(1-naphthylaminoformylmethyl)-1,13-diaza-4,7,10,19-
tetraoxa-16,22-dithiacyclotetracosane(20).
Ligand 20 (0.20 g, 53%) was obtained as viscous liquid from
0.20 g (0.5 mmole) of macrocyclic diamine 10 and 0.33 g (1.5
1
mmole) of 24 according to the general procedure; H nmr: δ 2.69
(t, J = 5.0 Hz, 4H), 2.85 (s, 4H), 2.90 (s, 4H), 2.98 (s, 4H), 3.27
(s, 4H), 3.41 (m, 4H), 3.44 (m, 4H), 3.53 (t, J = 4.5 Hz, 4H), 3.59
(t, J = 2.5 Hz, 4H), 7.44-7.52 (m, 6H), 7.65(d, J = 8.5 Hz, 2H),
[16] N. Su, J. S. Bradshaw, X. X. Zhang, H.-C. Song, G.-P.
Xue, P. B. Savage, K. E. Krakowiak and R. M. Izatt., J. Org. Chem.,
64, 8855 (1999).
[17] C.-T. Chen and W.-P. Huang, J. Am. Chem. Soc., 124,
6246 (2002).
[18] J. S. Bradshaw and R. M. Izatt, Acc. Chem. Res., 30, 338
(1997).
[19] R. M. Izatt, J. Incl. Phenom., 29, 197 (1997).
[20] J. S. Bradshaw, J. Incl. Phenom., 29, 221 (1997).
[21] M. Trkovik and Z. Ivezic, J. Heterocyclic Chem., 37, 137
(2000).
[22] K. C. Pandya, Current Sci., 8, 208 (1939).
[23] I. P. B. Mahajani and J. N. Ray, J. Ind. Chem. Soc., 33, 455
(1956).
7.82-7.84 (dd, J = 8.5 Hz, J = 1.5 Hz, 2H), 8.08 (t, J = 8.0 Hz,
4H), 10.11 (s, 2H); C nmr: δ 32.4, 33.5, 56.5, 56.7, 61.1, 70.3,
71.9, 72.0, 72.9, 121.3, 123.3, 127.0, 127.5, 127.6, 127.7, 128.7,
1
2
13
+
130.2, 134.4, 135.8, 172.5; ms (fab) for C
H
N O S (M+H) ,
40 53
4 6 2
+
calcd. 749.3, found, 749.3; hrms for C
calcd. 749.3406, found 749.3401.
H N O S (M+H) ,
40 53 4 6 2
Anal. Calcd. for C
H N O S : C, 64.14; H, 7.00. Found C,
40 52 4 6 2
64.42; H, 6.87.
Acknowledgements.
The authors thank the Scientific and Technical Commission of
Guangzhou, China, (98-J-013-01, 01-J-015-01), and the Ministry
[24] G. Kototos and C. Tzougraki, J. Heterocyclic Chem., 23,
87 (1986).