A convenient synthesis of new macrocyclic thioether-esters and ether-esters: Extraction properties of these esters for alkali, alkaline earth, and transition metal cations

Article abstract of DOI:10.1080/104265090902714

Macrocyclic thioether-esters and ether-esters have been prepared by treating 2,2′-dithiobenzoic acid dichloride and 1,2-benzendicarboxylic acid dichloride with appropriate glycols or dithiol. The complexing ability of these thioether-esters and ether-esters toward Li⁺, Na⁺, K⁺, Mg²⁺, Ca²⁺, Sr²⁺, Ba ²⁺, Co²⁺, and Ni²⁺ has been measured by the solvent extraction method. The extraction data indicate that compound 2 exhibits stronger selectivity toward Li⁺, 3 toward Ba²⁺, 4 toward K⁺, 5 toward Mg²⁺, 6 toward Ba²⁺ and Sr ²⁺, and 7 toward Co²⁺ and Ni²⁺ when compared with other cations. Copyright Taylor & Francis Inc.

Full text of DOI:10.1080/104265090902714

Phosphorus, Sulfur, and Silicon, 180:1953–1960, 2005
Copyright © Taylor & Francis Inc.
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/104265090902714
A Convenient Synthesis of New Macrocyclic
Thioether-Esters and Ether-Esters: Extraction Properties
of These Esters for Alkali, Alkaline Earth, and
Transition Metal Cations
Seyed Mohammad Seyedi
M. Shadkam
A. Ziafati
Department of Chemistry, School of Sciences, Ferdowsi University
of Mashhad, Mashhad, I. R. Iran
Macrocyclic thioether-esters and ether-esters have been prepared by treating 2,2ꢀ-
dithiobenzoic acid dichloride and 1,2-benzendicarboxylic acid dichloride with ap-
propriate glycols or dithiol. The complexing ability of these thioether-esters and
2+
ether-esters toward Li+, Na+, K+, Mg2+, Ca2+, Sr2+, Ba2+, Co2+, and Ni has
been measured by the solvent extraction method. The extraction data indicate that
compound 2 exhibits stronger selectivity toward Li+, 3 toward Ba2+, 4 toward K+,
2+
2+
2+
and Ni when
5 toward Mg2+, 6 toward Ba
and Sr2+, and 7 toward Co
compared with other cations.
INTRODUCTION
The synthesis and complexing properties of macrocyclic thiacrown
ethers have been the subject of increased interest during the past 2–3
decades.1−12 The formation of thiacrown macrocyclics containing a car-
bonyl group has also been reported.13−16 The synthesis of macrocyclic
ether-esters compounds,17 a wide variety of polyether-diester com-
pounds including ether-esters,18−25 thioether-esters,20,22,24,26 and ether-
thiolesters,20,24 was prepared by Bradshaw, Izatt, and Christensen
by coupling of either dibasic acid salts and α,ω-dihalo compounds or
dibasic acid chlorides and α,ω-dihydroxy compounds. Two macrocyclic
polyether-monoester compounds have been reported by Matsushima27
in a moderate yield. Edema and his colleagues28 have realized diketo-
functionalized thiocrown ethers in 38–57% yields.
Received August 24, 2004; accepted September 14, 2004.
Address correspondence to Seyed Mohammad Seyedi, Department of Chemistry,
School of Sciences, Ferdowsi University of Mashhad, Mashhad, 91775, I. R. Iran. E-mail:
smseyedi@yahoo.com
1953

1954
S. M. Seyedi et al.
In this article, we describe convenient synthesis and extraction
properties of macrocyclic ether-esters and thioether-esters which are
prepared by treating 2,2ꢀ-dithiodibenzoic acid with thionyl chloride and
appropriate glycol or dithiol. The present procedure does not require
the use of solvent [except 7] nor high dilution techniques and is much
more convenient than the reported procedures, providing the expected
macrocyclic esters in higher yields ranging from 71–85%.
RESULTS AND DISCUSSION
Refluxing 2,2ꢀ-dithiobenzoic acid with thionyl chloride for 14 h afforded
exclusively (TLC) the oily dark brown compound 1 which gave a white
AgCl deposit in a silver nitrate test. Compound 1 reacted with propylene
glycol in pyridine to give the oily brown 2 (Scheme 1).
SCHEME 1
Refluxing 1 with triethylene glycol in the presence of pyridine
for 1.5 h gave 3 (80%). Similarly, reaction of 1 by refluxing with
tetraethylene glycol and pyridine for 1.5 h afforded 4 (85%) (Scheme 1).
1,2-Benzenedicarboxylic acid dichloride was refluxed with triethylene

Macrocyclic Thioether-Esters and Ether-Esters
1955
glycol and tetraethylene glycol for 3.5 h to give 5 and 6, respectively,
(Scheme 2).
SCHEME 2
Apart from consistency with IR, NMR, and Mass spectroscopy, com-
pounds 2–6 gave no AgCl deposit in a silver nitrate test but gave a
positive indication with the hydroxamic acid test.
Reaction of 1,2-benzendicarboxylic acid dichloride with 1,2-
ethanethiol and pyridine at refluxing for 2 h gave only starting material
by TLC. Adding chloroform and refluxing for 22 h afforded exclusively
(TLC) compound 7 (85%) (Scheme 3).
SCHEME 3
These results clearly indicate that the cyclization of dicarboxylic acid
dichlorides with appropriate glycols does not need the use of a solvent
and especialy those macrocyclic esters with more atoms (i.e., 3 and
4) need less time to cyclize and give higher yields than the reported
procedures.13,20,24,26 In the case of 7, which is the smallest macrocyle
in this series, the need of the solvent and the difficulty for cyclization
might be due to the large size of SH groups in 1,2-ethandithiol. The
anticonformer may predominate, and after connecting one SH group
to 1,2-benzenedicarboxylic acid dichloride, either the SH or COCl
group must rotate into proper allignment, which is thermodynamically
difficult for both of them. Therefore, in the present of the solvent and
refluxing for longer times, this alignment is possible for the reaction to
occur.

1956
S. M. Seyedi et al.
Alkali, Alkaline Earth, and Transition Metal Picrate Extractions
The complexing abilities of compounds 2–7 were assessed by a sol-
vent extraction of alkali alkaline earth, and transition metal picrates
from an aqueous solution into dichloromethane according to Haines’s
procedure.29 The procedure was repeated three times to ensure com-
plete extraction. The extraction efficiency was determined by measur-
ing the absorbance of the picrate in the aqueous phase at 354 nm using a
UV spectrophotometer. The results are presented in Table I. These new
macrocyclic esters were found to have unique cation complexing prop-
erties which were opposite to those of typical crown ethers30 but compa-
rable with those of some naturally occuring macrocyclic antibiotics.18
Compound 7, due to the smaller number of sulfur ligands and also the
resonance between the loan pair of electrons of sulfur with the carbonyl
group, seems not able to complex strongly with Co2+ and Ni2+ cations.
The data in Table I indicates that compounds 2 exhibits stronger selec-
tivity towards Li+, 3 towards Ba2+, 4 towards K+, 5 towards Mg2+, 6
towards Ba2+ and Sr2+, and 7 towards Co2+ and Ni2+ when compared
with other cations. Factors such as the size of cavity, flexibility of macro-
cyclic ring,31−33 total number of ligands,34,35 substituents which cause
changing the conformation, and flexibility36 influence binding and ex-
traction selectivity.
EXPERIMENTAL
Solvents, reagents, and chemical materials were obtaind from Merck
and Fluka company. Melting points were measured on an Elec-
trothermal melting point apparatus. TLC analysis was performed on
TABLE I Alkali, Alkaline Earth, and Transition Metal Picrate
Extraction Data from Aqueous Solution into Dichloromethane by
using Compounds 2–7
Percent of picrate extracted (%)a
Cation
Crownb
Li+
Na+
K+
Mg2+
Ca2+
Sr2+
Ba2+
Co2+
Ni2+
2
3
4
5
6
7
1.36
0
0
9.95
0
0
0
0
2
4.5
1
16.08
0.6
0
0
0
0
0
0
0
0
0
0.73
0
0
0
0
0
0.64
7.50
4.74
7.11
10.27
0
12.93
10.94
11.44
20.39
0
7.7
4.05
6.08
3.17
0
14.37
6.53
9.15
17.64
0
34.24
6.84
12.32
17.81
0
aAverage for three samples.
bOrganic phase (dichloromethane): (2–7 macrocycles) = 7.0 × 10−4 M. Aqueous
phase: (picric acid) = 7.0 × 10−4 alkali, alkaline earth metal chloride; (transition metal
hydroxide) = 0.1 M

Macrocyclic Thioether-Esters and Ether-Esters
1957
kieselgel PG60 with 1:4 (v/v) ethyl acetate-chloroform (solvent A) or
1:4 (v/v) methanol-chloroform (solvent B). IR spectra were recorded
on a Shimadzu Fourier transform infrared spectrophotometer, model
4300. Proton NMR spectra were obtained by using a Bruker AC 100
Fourier transform spectrometer. Chemical shifts are reported in ppm
(δ) downfield from tetramethylsilane (TMS) as an internal standard. A
Shimadzu model A120 UV-visible spectrophotometer was used to mea-
sure absorbance at 354 nm in connection with the picrate extraction
experiments described below. Mass spectral (MS) data were recorded
on a Massens Poektrometer CH-VA spectrometer at 70 ev.
2,2ꢀ-Dithiobenzoic Acid Dichloride 1
A mixture of 2,2ꢀ-dithiobenzoic acid (0.3 g, 0.98 mmol) and thionyl chlo-
ride (0.46 g, 3.92 mmol) was refluxed for 14 h. TLC (solvent A) indicated
the complete disappearance of starting material (RF = 0.80) and the
presence of the product (RF = 0.77). Concentration of the mixture gave
the oily, brown compound 1 (0.23 g, 68%). IR (KBr) 1750 (CO), 700 cm−1
(CCl).1H NMR (CDCl3) δ 7.2–8.8 (8H, m, 2 × C6 H ). MS(m/s): M+
=
4
342.
7-Methyl-7,8-dihydro-5H,10H-dibenzo[j, f ][1, 4, 8, 9]-
dioxadithiacyclododecine-5,10-dione 2
To the mixture of 1 (1.022 g, 3 mmol) and pyridine (0.48 mL, 6 mmol)
in a water bath was added to propylene glycol (0.22 mL, 3 mmol), and
the new mixture was stirred vigorously for 2 h during which time it
turned oily and dark brown. Water (50 mL) was added, and the mixture
was extracted with chloroform (3 × 30 mL). The combined chloroform
extracts were dried (CaCl2) and concentrated. The oily residue was pu-
rified by colum chromatography (ethyl acetate:chloroform, 1:4 v/v) to
give the oily, brown 2 (0.32 g, 31%). IR (KBr) 1730 cm−1 (CO). 1H NMR
(CDCl3) δ 1.48 (3H, d, CH ), 3.8–4.2 (1 H, m, CH CH3), 5.4 (2H, d,
3
OCH ), 7.2–8.2 (8 H, m, 2 × C6 H ). MS (m/z): M+ = 346.
2
4
7,8,10,11,13,14-Hexahydro-5H,16H-dibenzo[p,l]-
[1,4,7,10,14,15]tetraoxadithia-cyclooctadecine-5,16-dione 3
A mixture of 1 (0.98 g, 2.8 mmol), pyridine (0.45 mL, 5.6 mmol), and tri-
ethylene glycol (0.34 mL, 2.8 mmol) was refluxed for 1.5 h. TLC (solvent
A) indicated the complete disappearance of the starting material (RF
= 0.77) and the presence of the product (RF = 0.36). The mixture was
worked up exactly as described for 2 and gave the oily, dark brown 3

1958
S. M. Seyedi et al.
(0.94 g, 80%). IR (KBr) 1735 cm−1 (CO). 1H NMR (CDCl3) δ 3.5–3.8 (8H,
m, CH ), 4.5 (4H, t, OCH ), 7.2–8.3 (8H, m, 2×C6 H ). MS(m/z):
2
2
4
M+ = 420.
13,14,16,17,19,2,22,23-Octahydro-11 H, 25H-Dibenzo[s, o]
[1,4,7,10,13,17,18] Pentaoxadithiacycloheneicosane-11,
25-Dione 4
A mixture of 1 1.0 g, 1.45 mmol), pyridine (0.23 mL, 2.9 mmol), and
tetraethylene glycol (0.25 mL, 1.45 mmol) was heated under reflux for
1.5 h. TLC (solvent A) indicated the complete disappearance of the start-
ing material (RF = 0.77) and the presence of product (RF = 0.28). The
mixture was workedup exactly as described for 2 and gave the oily, dark
brown 3 (0.57 g, 85%). IR (KBr) 1730 cm−1 (CO). 1H NMR (CDCl3) δ 3.7–
3.9 (12H, m, CH ), 4.5 (4H, t, OCH ), 7.2–8.2 (8H, m, 2 × C6 H ).
2
2
4
MS(m/z): M+ = 464.
3,4,7,9,10-Hexahyro-2,5,8,11-benzotetraoxacyclotetradecine-
1,12-dione 5
A mixture of 1,2-benzenedicarbonyl dichloride (0.28 mL, 2 mmol), pyri-
dine (0.32 mL, 4 mmol), and triethylene glycol (0.24 mL, 2 mmol) was
heated under reflux for 3.5 h. TLC (solvent B) indicated the complete
disappearance of the starting material (RF = 0.83) and the presence
of the product (RF = 0.95). The mixture was worked up exactly as de-
scribd for 2 and gave the oily, yellow 5 (0.4 g, 71%). IR (KBr) 1730 cm−1
(CO). 1H NMR (CDCl3) δ 3.7–3.9 (8H, m, CH ), 4.5 (4H, t, OCH ),
2
2
7.45–7.9 (4H, m, C6 H ). MS (m/z): M+ = 280.
4
3,4,6,7,9,10,12,13-octahydro-2,5,8,11,14-
benzopentaoxacycloheptadecine-1,15-dione 6
A mixture of 1,2-benzendicarbonyl dichloride (0.28 mL, 2 mmol), pyri-
dine (0.32 mL, 4 mmol), and tetraethylene glycol (0.35 mL, 2 mmol) was
refluxed for 3.5 h. TLC (solvent B) indicated the complete disappear-
ance of starting material (RF = 0.83) and the presence of the product
(RF = 0.92). The mixture was worked up exactly as described for 2 and
gave the oily, yellow 6 (0.49 g, 76%). IR (KBr) 1740 cm−1 (CO). 1H NMR
(CDCl3 ) δ 3.6–3.8 (12H, m, CH -), 4.45 (4H, t, OCH -), 7.5–7.9 (4H,
2
2
m, C6 H ). MS (m/z): M+ = 324.
4

Macrocyclic Thioether-Esters and Ether-Esters
1959
3,4-Dihydro-2,5-benzoditiocine-1,6-dione 7
A mixture of 1,2-benzenedicarbonyl dichloride (0.29 mL, 2 mmol), pyri-
dine (0.32 mL, 4 mmol), and 1,2-ethanedithoil (0.33 mL, 2 mmol) was
heated under reflux for 2 h, during which it showed no indication of
product (TLC, solvent A). Chloroform (10 mL) was added to the mix-
ture and heating continued for 22 h. TLC (solvent A) indicated the
complete disappearance of the starting material (RF = 0.83) and the
presence of product (RF = 0.88). Water (30 mL) was added, and the or-
ganic layer was separated, dried (CaCl2), and concentrated to dryness.
The crystalline solid that was obtained was recrystallized (CH2Cl2) to
1
give white, crystalline 7 (0.38 g, 85%). IR (KBr) 1730 cm−1 (CO). H
NMR (CDCl3) δ 3.7 (4H, s, CH ), 7.6–7.99 (4H, m, C6 H ). MS (m/z):
2
4
M+ = 224.
Extraction Measurement
An aqueous solution (15 mL) containing picric acid (7.0 × 10−4 M), al-
kali, an alkaline earth metal chloride (0.1 M), and a transition metal
hydroxide (0.1 M) was vigorously shaken with an equal volume of
dichloromethane containing macrocyclics 2–7 (7.0 × 10−4 M) for 15 min.
The absorbance, A, of the aqueous layer before and after the extraction
experiment, Ao and Ae, respectively, was measured at the position of
maximum absorption (354 nm). The percentage of extraction of alkali,
alkaline, and transition metal picrates into the organic layer was cal-
culated by the expression 100 (Ao–Ae)/Ao. Results are given in Table I.
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