Synthesis of new benzo-substituted macrocyclic ligands containing pyridine or triazole as subcyclic units

Article abstract of DOI:10.1016/S0040-4020(99)01068-6

The macrocyclic diamides 11-21, 42 and 43 were prepared by nucleophilic reaction of the bis phenols 22-29 with the appropriate dihalo compounds 2, 3, 40 and 41, respectively. The macrocyclic dithiodiamides 30-33 were obtained in good yields upon treatment

Full text of DOI:10.1016/S0040-4020(99)01068-6

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 885–895
Synthesis of New Benzo-substituted Macrocyclic Ligands
Containing Pyridine or Triazole as Subcyclic Units
*
Ahmed H. M. Elwahy and Ashraf A. Abbas
Department of Chemistry, Faculty of Science, Cairo University, Giza, A. R. Egypt
Received 16 September 1999; revised 17 November 1999; accepted 2 December 1999
Abstract—The macrocyclic diamides 11–21, 42 and 43 were prepared by nucleophilic reaction of the bis phenols 22–29 with the
appropriate dihalo compounds 2, 3, 40 and 41, respectively. The macrocyclic dithiodiamides 30–33 were obtained in good yields upon
treatment of 11, 13, 15 and 17 with Lawesson’s reagent. The macrocycles 61–63 were prepared by condensation of the bis(aldehyde) 37 with
the appropriate bis(aminotriazoles) 50–54 to give the corresponding Schiff bases 56–60 followed by NaBH4 reduction. ᭧ 2000 Elsevier
Science Ltd. All rights reserved.
Introduction
In connection with these findings and in continuation of our
interest in synthesizing macrocyclic crown compounds and
their precursors from salicylic acid derivatives,22–25 we
report here the synthesis of a series of 17–19 and 25-26-
membered benzo-fused macrocyclic diamides containing
pyridine as a subcyclic unit. We also describe our attempts
to synthesize benzo-fused macrocycles upon which are
fused pyridine and triazole units and containing N, O and
S inside the macrocyclic ring as donor atoms.
Heterocyclic groups incorporated in a macrocyclic ring
provide rigidity and are able to participate in complexation
through their soft donor atoms; for example macrocyclic
ethers with pyridine and other nitrogen containing hetero-
cyclic subunits were reported to form strong and selective
interactions with various charged and neutral guest
molecules.1–5 If additional benzonuclei are condensed,
ligand properties are altered. As a rule the complexation
of cations decreases6 due to the lower donor capacity of
benzo compared to aliphatic bonded heteroatoms and as a
consequence of conformational hindrance. On the other
hand, the complexation of uncharged organic molecules is
promoted.7 In order to improve the binding ability of macro-
cyclic receptors for alkali metal cations, much attention has
been paid to the development of functional groups in the
ring.8–11 For example incorporation of an amide linkage in a
polyether macrocycle may modify the binding properties of
crown ether compounds to favour the alkali earth cation
over alkali metal cations.12–16 Gokel and coworkers have
found that diaza-18-crown-6 derivatives with amide groups
in their side arms exhibit extraordinary Ca2ϩ binding
strength and remarkable selectivity for Ca2ϩ over Naϩ,17
while a number of synthetic cyclopeptides are Kϩ or Ca2ϩ
ionophones.18 Also macrocyclic diamides are precursors in
the preparation of diazacrown compounds which are used as
molecular receptors and for the synthesis of cryptands and
related compounds.19,20 Moreover some macrocyclic
diamides have been recently used as new catalysts in the
highly regioselective halogenation cleavage of epoxides
with elemental halogens.21
Results and Discussion
Several synthetic methods have been developed for the
synthesis of macrocyclic diamides. Among these methods
the high dilution technique is often used as the most versa-
tile procedure.19 This technique requires the simultaneous
addition of a bis acid chloride and a diamino ether to a large
volume of solvent over an extended period. Recently,
Sharghi and coworkers26 reported the synthesis of similar
systems in good yields by reacting a diacid dichloride with
a diamine in dichloromethane without the use of high
dilution techniques. Using the above technique, Vogtle
and others27–33 have reported the synthesis of macrocyclic
diamides containing pyridine as the subcyclic unit. In most
cases 2,6-bis(chlorocarbonyl)pyridine was chosen as the
starting material. The produced macrocycles in most cases
have the amide linkage directly attached to the pyridine
ring. We have now studied two synthetic routes towards
modified derivatives of these macrocycles as outlined in
Scheme 1. In the first route we applied a similar approach
to that described by Sharghi et al.26 for the synthesis of the
macrocyclic diamides 11 and 17. Thus, reaction of the
potassium salt 1 (obtained upon treatment of methyl salicyl-
ate with methanolic potassium hydroxide solution) with 2,6-
bis(bromomethyl)pyridine (2) in boiling DMF gave the
Keywords: triazole; pyridine; macrocyclic ligands.
* Corresponding author. E-mail: aelwahy@hrzpub.tu-darmstadt.de
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(99)01068-6

886
A. H. M. Elwahy, A. A. Abbas / Tetrahedron 56 (2000) 885–895
Scheme 1.
corresponding diester 4 in 55% yield. Saponification of 4
followed by acid treatment afforded the dicarboxylic acid 6
in 62% yield. Treatment of 6 with SOCl2 gave the corre-
sponding dicarboxylic acid dichloride 8. Cyclization was
carried out with the fast addition of ethylenediamine (10)
in CH2Cl2 into a solution of 8 in the same solvent. After
vigorous stirring for 20 min at room temperature the
macrocyclic diamide 11 was obtained in 6% yield. Simi-
larly, the tribenzo analogue 17 was prepared in 8% yield by
cyclization of the diacid dichloride 9 with ethylenediamine.
Compound 9 was obtained by first reacting 1 with 1,3-di-
(bromomethyl)benzene 3 in refluxing DMF to give 5 in 60%
yield followed by saponification to give 7 in 70% yield.
Reaction of the latter with SOCl2 afforded the corresponding
dicarboxylic acid dichloride 9. Attempts to improve the
yields of 11 and 17 by repeating the above reactions under
the high dilution technique were unsuccessful. In anticipa-
tion of the low yield of the macrocyclic diamides 11, 17 we

A. H. M. Elwahy, A. A. Abbas / Tetrahedron 56 (2000) 885–895
887
Scheme 2.
now apply our recently reported synthetic route for prepara-
tion of similar systems.22 Thus, the bis phenol 22 was
converted into its dipotassium salt upon treatment with
methanolic KOH solution. Treatment of the salt with each
of 2 and 3 in refluxing DMF for 5 min afforded 11 and 17 in
35 and 50% yield, respectively. Similarly, the macrocyclic
diamides 12–16, 18–21 could be obtained in 35–55%
yields by reacting the potassium salt of the appropriate bis
phenols 22,22 23,34 24,35 (25, 28),36 26, 27, 29 with each of 2
and 3 in refluxing DMF. It is noteworthy that this reaction
proceeds in a short time affording moderate to good yields
of the macrocycles. The present findings are comparable to
our recently reported synthesis of similar systems where
reasonable explanations were given.22 The new bis azo
compounds 26, 27, 29 were prepared by coupling the corre-
sponding bis phenols 25 and 28 with two equivalents of the
appropriate arenediazonium chloride in aqueous NaOH
solution. The arylazo groups in the latter compounds were
proved by 1H NMR study to occupy the 5-postion of the aryl
group and excluded the possible formation of the other
isomeric azo derivatives.34 The introduction of the bis azo
groups in the macrocycles as potential chromophores should
be useful for spectrophotometric applications.
corresponding di(methylthio) derivative 34 in 50% yield.
The structure of the latter was chemically established by
its ready oxidation with H2O2 in refluxing acetic acid to
give the corresponding 35 in 60% yield. Compound 35
was alternatively obtained in 65% yield by oxidation of
11 with H2O2 in refluxing acetic acid.
In an attempt to extend the spacing between the terminal bis
functional group in compounds 2 and 3 and to increase
the number of intervening ether functions we also report
the synthesis of the novel 25-26-membered macrocyclic
diamides 42 and 43 as outlined in Scheme 3.
Thus, salicylaldehyde was converted to its potassium salt
upon treatment with methanolic KOH. Reaction of the latter
with each of 2 and 3 in boiling DMF afforded the corre-
sponding bis aldehyde derivatives 36, 37 in 50 and 60%
yields, respectively. Reduction of 36 and 37 with NaBH4
gave the corresponding bis(hydroxymethyl) ethers 38, 39
in 60–80% yields, which on treatment with SOCl2 in
CHCl3 gave the corresponding bis(chloromethyl) ethers
40, 41 in 70 and 75% yields, respectively. Macrocycles 42
and 43 were obtained in 8–10% yields by heating the dipo-
tassium salts of each of 22, 26 with 40 and 41, respectively.
The novel macrocyclic diamides, now available, prompted
us to study their possible transformation to other
functionalised derivatives (Scheme 2).
Our study was extended to investigate the reactivity of the
bis aldehyde 36 towards the bis(aminotriazole) derivatives
50–52,37 53, 54 (prepared by heating the dibromo alkanes
47–49 with 4-amino-1,2,4-triazole derivatives 44–46 in
aqueous ethanol (50%) containing NaOH) in an attempt to
obtain the corresponding novel macrocycles 56–60 (XˆN)
(Scheme 4).
The dithiodiamides 30–33 were obtained in 50–72% yields
upon treatment of 11, 13, 15 and 17 with Lawesson’s
reagent in refluxing toluene. Treatment of 30 with MeI in
methanolic sodium methoxide solution afforded the

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A. H. M. Elwahy, A. A. Abbas / Tetrahedron 56 (2000) 885–895
889
Scheme 4.
However, the reaction of bis(aminotriazoles) 50–54 with 36
in refluxing acetic acid under the high dilution conditions
did not afford the corresponding pyridinomacrocycles
but gave instead the 2,6-bis[benzo(b)furan-2-yl]pyridine
55 in 50% yield. The latter could be obtained by heating
only 36 in refluxing acetic acid. On the other hand,
reaction of 37 with the bis amino derivatives 50–54 in
refluxing acetic acid under the high dilution conditions
afforded the corresponding Schiff bases 56–60 in 55–
62% yields. Reduction of these with NaBH4 gave the
corresponding macrocycles 61–63 in 65–75% yields.
We attribute the reactivity of the methylene group in
compound 36 compared to 37 to the greater electron
withdrawing effect of C-2 and C-6 in the pyridine ring
especially when protonated.
In conclusion, we prepared a series of new benzo-
substituted macrocyclic-diamides containing pyridine as
the subcyclic unit and their corresponding dithiodiamide
derivatives. Contrary to the other known pyridinomacro-
cyclic diamides, the amide group in the macrocyclic ring
is not directly attached to the pyridine unit. This should
modify the cation binding ability of the new macrocycles.
Some derivatives showed promising cation binding proper-
ties in a preliminary spectrophotometric study, which is still
under way. We also prepared a series of new macrocycles

890
A. H. M. Elwahy, A. A. Abbas / Tetrahedron 56 (2000) 885–895
1
upon which are fused three benzo and two triazole rings and
containing N, O and S as donor atoms. Further studies to
develop new synthetic routes to introduce the pyridine ring
into these macrocycles are in progress.
(lit.39 mp 115–117ЊC); H NMR (CDCl3) d 5.19 (s, 4H,
OCH2), 6.90–7.33 (m, 12H, ArHs), 10.36 (s, 2H, CHO)
ppm.
Synthesis of compounds 6 and 7
Experimental
General procedure. A solution of each of 4 and 5 (0.1 mol)
in 10% aqueous KOH (500 ml) was refluxed for 3 h. The
mixture was cooled, washed and acidified with 6 N HCl and
the solid obtained was collected and crystallized from
ethanol as colorless crystals of 6 and 7, respectively.
All melting points are uncorrected. IR spectra (KBr) were
recorded on a Perkin–Elmer 1430 spectrophotometer. NMR
spectra were measured with a Varian GEMINI 200 spectro-
meter (200 MHz 1H NMR) or Brucker WM-300 instrument
and chemical shifts are given in ppm from TMS. Mass
spectra were recorded on a Varian 311 A or DCMS-QP
1000 EX (EI, 70 eV) or Field Desorption (FD). Elemental
analyses were carried out at the Microanalytical Centre,
Cairo University. 1,2-Diaminoethane, 1,3-diaminopropane,
1,4-diaminobutane and 1,4-dibromobutane were used as
purchased from Aldrich.
2,6-Bis[2-(carboxyphenoxy)methyl]pyridine (6). (62%),
mp 185–187ЊC; IR (cmϪ1) 2557–2400 (OH), 1720
1
(CyO); H NMR (DMSO) d 12.71 (brs, 2H, COOH), 5.31
(s, 4H, OCH2), 7.01–8.11 (m, 11H, ArHs) ppm. (Calcd for
C21H17NO6 (379.37): C, 66.49; H, 4.52; N, 3.69. Found: C,
66.70; H, 4.60; N, 3.30).
1,3-Bis[2-(carboxyphenoxy)methyl]benzene (7). (70%),
mp 153–155ЊC; IR (cmϪ1) 2555–2360 (OH), 1747
(CyO); H NMR (CDCl3) d 12.81 (brs, 2H, COOH), 5.32
Synthesis of compounds 4, 5, 36 and 37
1
General procedure. Each of methyl salicylate (1) and sali-
cylaldehyde (20 mmol) was dissolved in hot ethanolic KOH
(prepared by dissolving 1.12 g (20 mmol) of KOH in 20 ml
of absolute ethanol), and the solvent was then removed in
vacuo. The remaining material was dissolved in DMF
(15 ml) and the appropriate dibromide 2, 3 (10 mmol) was
added. The reaction mixture was refluxed for 5 min during
which KCl was separated. The solvent was then removed in
vacuo and the remaining materials was washed with water
and purified by crystallization to give compounds 4, 36, 37
or by chromatography to give compound 5.
(s, 4H, OCH2), 7.09–8.19 (m, 12H, ArHs) ppm. (Calcd for
C22H18O6 (378.38): C, 69.83; H, 4.79. Found: C, 69.80; H,
5.00).
2,6-Bis(2-chloroformylphenoxymethyl)pyridine (8), 1,3-
bis(2-chloroformylphenoxymethyl)benzene (9). A solu-
tion of each of 6 and 7 (10 mmol) in SOCl2 (10 ml) was
heated under reflux for 2 h. The solvent was then removed in
vacuo and the remaining material was used in the next step
without further purification.
Preparation of the potassium salts of 22–29
2,6-Bis[2-(methoxycarbonylphenoxy)methyl]pyridine (4).
With the use of the general procedure, the potassium salts of
1 and 2 gave crude 4 which crystallized from methanol as
colorless crystals (55%), mp 158–60ЊC; 1H NMR (CDCl3) d
3.99 (s, 6H, CH3), 5.63 (s, 4H, OCH2), 7.04–8.27 (m, 11H,
ArHs) ppm. (Calcd for C23H21NO6 (407.42): C, 67.81; H,
5.20; N, 3.44. Found: C, 67.50; H, 5.30; N, 3.70.
A solution of each of compounds 22–29 (10 mmol) and
KOH (1.14 g, 20 mmol) in ethanol (10 ml) was stirred at
room temperature for 10 min. The solvent was then
removed in vacuo and the remaining solid was triturated
with dry ether, collected, dried, and used in the next step
without further purification.
1,3-Bis[2-(methoxycarbonylphenoxy)methyl]benzene (5).
With the use of the general procedure, the potassium salt of
1 and 3 gave crude 5 as an oil which purified by chromato-
graphy over a silica gel column using CHCl3 as an eluent
(60%), 1H NMR (CDCl3) d 3.84 (s, 6H, CH3), 5.12 (s, 4H,
OCH2), 6.94–7.83 (m, 12H, ArHs) ppm. (Calcd for
C24H22O6 (406.43): C, 70.93; H, 5.46. Found: C, 70.70; H,
5.30).
Synthesis of the cyclic diamides 11–21, 42, 43
General procedure A. A solution of each of the appropriate
potassium salt of 23–29 (10 mmol) and the appropriate
dichloro compound 2, 3 and 40, 41 (10 mmol) in DMF
(20 ml) was heated under reflux for 15 min during which
KCl was precipitated. The solvent was then removed in
vacuo and the remaining material was washed with water
(50 ml) and crystallized from the proper solvent to give
compounds 11–21 and 42, 43, respectively.
2,6-Bis[2-(formylphenoxy)methyl]pyridine (36). With the
use of the general procedure, the potassium salt of salicyl-
aldehyde 35 and 2 gave crude 36 which crystallized
from ethanol as colorless crystals, (50%), mp 145–146ЊC
General procedure B: (for compounds 11 and 17). A
solution of ethylenediamine (10 mmol) and triethylamine
(40 mmol) in CH2Cl2 (250 ml) was added quickly (5 s) to
a vigorously stirring solution of diacid chloride 8, 9
(10 mmol) in CH2Cl2 (250 ml) at 0ЊC. The reaction mixture
was stirred at room temperature for 10–30 min. The pre-
cipitate was filtered off and the filtrate washed with water
(2×100 ml) and 10% aqueous NaOH solution (100 ml) and
then water (100 ml). The organic layer was dried over
1
(lit.38 mp 141–145ЊC); H NMR (CDCl3) d 5.31 (s, 4H,
OCH2), 7.09–7.88 (m, 11H, ArHs), 10.55 (s, 2H, CHO)
ppm.
1,3-Bis[2-(formylphenoxy)methyl]benzene (37). With the
use of the general procedure, the potassium salt of salicyl-
aldehyde 35 and 3 gave crude 37 which crystallized
from ethanol as colorless crystals, (60%) mp 114–116ЊC

A. H. M. Elwahy, A. A. Abbas / Tetrahedron 56 (2000) 885–895
891
MgSO4 and the solvent was evaporated to give compounds
11 and 17, respectively.
CH2CH2NH), 3.16 (m, 4H, CH2NH), 5.27 (s, 4H, OCH2),
7.08–8.03 (m, 13H, ArHs, NH) ppm. (Calcd for
C25H35N3O4 (431.49): C, 69.59; H, 5.84; N, 9.74. Found:
C, 69.30; H, 5.50; N, 9.60).
7,11-Nitrilo-2,12,20,21-tetrahydrodibenzo[b, j][1,12,5,8]-
dioxadiazacyclononadecin-18,23(19H,22H)-dione (11).
With the use of the general procedure A, the potassium
salt of 22 and 2 gave crude 11 which crystallized from
ethanol as colorless crystals (35%), mp 255–256ЊC; IR
(cmϪ1) 3396 (NH), 1647 (CyO); MS: m/z 404 (Mϩϩ1,
7,11-Nitrilo-2,16-di( p-methylphenylazo)-6,12,20,21,22,23-
hexahydrodibenzo[b,l][1,14,5,10]dioxadiazacyclohenicosin-
18,25(19H,24H)-dione (16). With the use of the general
procedure A, the potassium salt of 29 and 2 gave crude 16
which crystallized from acetic acid as yellow crystals
1
30%); H NMR (CDCl3) d 3.62 (m, 4H, CH2NH), 5.24 (s,
4H, OCH2), 7.01–8.18 (m, 13H, ArHs, NH) ppm; 13C NMR
(CDCl3) d 40.27 (CH2N), 70.12 (OCH2), 113.6, 121.06,
122.95, 130.67, 132.24, 137.81 (ArCHs), 123.09, 155.31,
155.72 (ArCs), 164.97 (CyO) ppm. (Calcd for C23H21NO4
(403.44): C, 68.47; H, 5.25; N, 10.42. Found: C, 68.70; H,
5.40; N, 10.60).
(50%), mp 230–232ЊC; H NMR (DMSO) d 1.22 (brs,
1
4H, CH2CH2NH), 2.41 (s, 6H, CH3), 3.16 (brs, 4H,
CH2NH), 5.28 (s, 4H, OCH2), 6.95–8.03 (m, 19H, ArHs,
NH) ppm. (Calcd for C39H37N7O9 (667.78): C, 70.15; H,
5.58; N, 14.68. Found: C, 70.30; H, 5.70; N, 14.90).
7,11-Metheno-2,12,20,21-tetrahydrodibenzo[b, j][1,12,5,8]-
dioxadiazacyclononadecin-18,23(19H,22H)-dione (17).
With the use of the general procedure A, the potassium
salt of 22 and 3 gave crude 17 which crystallized from acetic
With the use of the general procedure B, 8 and 10 gave 11
(6%).
7,11-Nitrilo-2,16-di(p-methylphenylazo)-2,12,20,21-tetra-
hydrodibenzo[b, j][1,12,5,8]dioxadiazacyclononadecin-
18,23(19H,22H)-dione (12). With the use of the general
procedure A, the potassium salt of 24 and 2 gave crude 12
which crystallized from acetic acid as yellow crystals
(50%), mp 290–292ЊC; IR (cmϪ1) 3379 (NH), 1645
acid as colorless crystals (50%), mp 290–292ЊC; IR (cmϪ1
)
1
3394 (NH), 1639 (CyO); MS: m/z 402 (Mϩ, 4.8%); H
NMR (DMSO) d 4.0 (m, 4H, CH2NH), 5.84 (s, 4H,
OCH2), 7.49–8.89 (m, 14H, ArHs, NH) ppm; 13C NMR
(DMSO) d 40.2 (CH2N), 68.9 (OCH2), 113.05, 120.74,
125.46, 127.34, 128.27, 130.62, 132.17 (ArCHs), 122.95,
137.05, 155.56 (ArCs), 165.23 (CyO) ppm. (Calcd for
C24H22N2O4 (402.45): C, 71.63; H, 5.51; N, 6.96. Found:
C, 71.90; H, 5.20; N, 6.80).
1
(CyO); MS: m/z 640 (Mϩ, 16.1%); H NMR (DMSO) d
2.41 (s, 6H, CH3), 3.50 (brs, 4H, CH2NH), 5.47 (s, 4H,
OCH2), 7.38–8.51 (m, 19H, ArHs, NH) ppm. (Calcd for
C37H33N7O4 (639.71): C, 69.47; H, 5.20; N, 15.33. Found:
C, 69.30; H, 5.40; N, 15.00).
With the use of the general procedure B, 9 and 10 gave 17
(8%).
7,11-Nitrilo-22H-6,12,20,21-tetrahydrodibenzo[b,k]-
[1,13,5,9]dioxadiazacycloeicosin-18,24(19H,23H)-dione
(13). With the use of the general procedure A, the potassium
salt of 25 and 2 gave crude 13 which crystallized from
methanol as colorless crystals (40%), mp 215–217ЊC; IR
(cmϪ1) 3396 (NH), 1643 (CyO); MS: m/z 417 (Mϩ,
7,11-Metheno-2,16-diphenylazo-2,12,20,21-tetrahydro-
dibenzo[b, j][1,12,5,8]dioxadiazacyclononadecin-
18,23(19H,22H)-dione (18). With the use of the general
procedure A, the potassium salt of 23 and 3 gave crude 18
which crystallized from acetic acid as yellow crystals
(55%), mp 228–230ЊC; IR (cmϪ1) 3406 (NH), 1643
(CyO); MS (FD): m/z 611 (Mϩϩ1, 100%); 1H NMR
(DMSO) d 3.52 (brs, 4H, CH2NH), 5.46 (s, 4H, OCH2),
7.01–8.50 (m, 22H, ArHs, NH) ppm. (Calcd for
C36H30N6O4 (610.67): C, 70.81; H, 4.95; N, 13.76. Found:
C, 70.90; H, 4.60; N, 14.00).
1
23.7%); H NMR (CDCl3) d 1.84 (quintet, Jˆ6.2 Hz, 2H,
CH2CH2NH), 3.51 (m, 4H, CH2NH), 5.29 (s, 4H, OCH2),
7.08–8.41 (m, 13H, ArHs, NH) ppm. (Calcd for
C24H33N3O4 (417.46): C, 69.05; H, 5.55; N, 10.70. Found:
C, 68.90; H, 5.60; N, 10.30).
7,11-Nitrilo-22H-2,16-di(p-methylphenylazo)-6,12,20,21-
tetrahydrodibenzo[b,k][1,13,5,9]dioxadiazacycloeicosin-
18,24(19H,23H)-dione (14). With the use of the general
procedure A, the potassium salt of 26 and 2 gave crude 14
which crystallized from acetic acid as orange crystals
(55%), mp 260–262ЊC; IR (cmϪ1) 3394 (NH), 1649
7,11-Metheno-22H-6,12,20,21-tetrahydrodibenzo[b,k]-
[1,13,5,9]dioxadiazacycloeicosin-18,24(19H,23H)-dione
(19). With the use of the general procedure A, the potassium
salt of 25 and 3 gave crude 19 which crystallized from acetic
acid as colorless crystals (40%), mp 268–270ЊC; IR (cmϪ1
)
1
(CyO); H NMR (CDCl3) d 1.93 (quintet, Jˆ6.1 Hz, 2H,
3379 (NH), 1637 (CyO); 1H NMR (CDCl3) d 1.39 (quintet,
Jˆ6.6 Hz, 2H, CH2CH2NH), 3.33 (m, 4H, NHCH2), 5.15
(s, 4H, OCH2), 7.09–8.21 (m, 14H, ArHs, NH) ppm.
(Calcd for C25H24N2O4 (416.47): C, 72.10; H, 5.81; N,
6.73. Found: C, 72.21; H, 5.70; N, 6.80).
CH2CH2NH), 2.42 (s, 6H, CH3), 3.57 (m, 4H, CH2NH), 5.35
(s, 4H, OCH2), 7.19–8.70 (m, 19H, ArHs, NH) ppm. (Calcd
for C38H35N7O4 (653.74): C, 69.82; H, 5.40; N, 15.00.
Found: C, 69.70; H, 5.20; N, 14.70).
7,11-Nitrilo-6,12,20,21,22,23-hexahydrodibenzo[b,l]-
[1,14,5,10]dioxadiazacyclohenicosin-18,25(19H,24H)-
dione (15). With the use of the general procedure A, the
potassium salt of 28 and 2 gave crude 15 which crystallized
from dil. acetic acid as colorless crystals (45%), mp 239–
240ЊC; IR (cmϪ1) 3398 (NH), 1649 (CyO); MS: m/z 431
(Mϩ, 15.1%); 1H NMR (DMSO) d 1.21 (brs, 4H,
7,11-Metheno-22H-6,16-di(p-methoxyphenylazo)-
6,12,20,21-tetrahydrodibenzo[b,k][1,13,5,9]dioxadiaza-
cycloeicosin-18,24(19H,23H)-dione (20). With the use of
the general procedure A, the potassium salt of 27 and 3 gave
crude 20 which crystallized from DMF as orange crystals
(45%), mp 320–322ЊC; IR (cmϪ1) 3382 (NH), 1652 (CyO);
MS: m/z 684 (Mϩ, 4.33%); 1H NMR (DMSO) d 1.55

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A. H. M. Elwahy, A. A. Abbas / Tetrahedron 56 (2000) 885–895
(quintet, Jˆ6.3 Hz, 2H, CH2CH2NH), 3.36 (brs, 4H,
NHCH2), 3.88 (s, 6H, OCH3), 5.35 (s, 4H, OCH2), 7.12–
8.18 (m, 20H, ArHs, NH) ppm. (Calcd for C39H36N6O6
(684.75): C, 68.41; H, 5.30; N, 12.27. Found: C, 68.20; H,
5.60; N, 11.90).
(brs, 2H, CH2CH2NH), 2.42 (s, 6H, CH3), 3.23 (m, 4H,
CH2NH), 7.07–8.52 (m, 14H, ArHs), 9.21 (brs, 2H, NH),
12.95 (s, 2H, OH) ppm. (Calcd for C31H30N6O4 (550.62): C,
67.62; H, 5.49; N, 15.26. Found: C, 67.70; H, 5.70; N,
14.90).
7,11-Metheno-6,12,20,21,22,23-hexahydrodibenzo[b,l]-
[1,14,5,10]dioxadiazacyclohenicosin-18,25(19H,24H)-
dione (21). With the use of the general procedure A, the
potassium salt of 28 and 3 gave crude 21 which crystallized
from acetic acid as colorless crystals (35%), mp 258–
260ЊC; IR (cmϪ1) 3375 (NH),1643 (CyO); 1H NMR
(CDCl3) d 1.13 (brs, 4H, CH2CH2NH), 3.24 (brs, 4H,
NHCH2), 5.11 (s, 4H, OCH2), 7.08–8.26 (m, 14H, ArHs,
NH) ppm. (Calcd for C26H26N2O4 (398.50): C, 78.36; H,
6.58; N, 7.03. Found: C, 78.40; H, 6.70; N, 7.20).
1,3-Bis(2-hydroxy-5-p-methoxylphenylazobenzoyl-
amino)propane (27). With the use of the general procedure,
p-anisidine was diazotized and coupled with 25 to give
crude 27 which crystallized from DMF/water as brown
1
crystals (60%), mp 224–225ЊC, H NMR (DMSO) d 1.93
(brs, 2H, CH2CH2NH), 3.44 (m, 4H, CH2NH), 3.87 (s, 6H,
OCH3), 7.06–8.49 (m, 14H, ArHs), 9.19 (brs, 2H, NH),
13.22 (s, 2H, OH) ppm. (Calcd for C31H30N6O6 (582.61):
C, 63.91; H, 5.19; N, 14.42. Found: C, 64.10; H, 5.30; N,
14.70).
13,17-Nitrilo-6,12,18,24,32,33-hexahydrotetrabenzo-
[b, f,n,r][1,5,16,20,9,12]tetraoxadiazacycloheptacosin-
30,35(31H,34H)-dione (42). With the use of the general
procedure A, the potassium salt of 23 and 40 gave crude
42 which crystallized from ethanol as colorless crystals
(8%), mp 178–179ЊC; IR (cmϪ1) 3385 (NH), 1649
1,3-Bis(2-hydroxy-5-p-methylphenylazobenzoylamino)-
butane (29). With the use of the general procedure,
p-toluidine was diazotized and coupled with 28 to give
crude 29 which crystallized from ethanol as yellow crystals
(65%), mp 210–212ЊC, 1H NMR (DMSO) d 1.64 (brs, 4H,
CH2CH2NH), 2.4 (s, 6H, CH3), 3.23 (brs, 4H, CH2NH),
6.85–8.54 (m, 14H, ArHs), 8.86 (brs, 2H, NH), 12.74 (s,
2H, OH) ppm. (Calcd for C32H32N6O4 (564.64): C, 68.07; H,
5.71; N, 14.88. Found: C, 67.95; H, 5.65; N, 14.95).
1
(CyO); MS: m/z 616 (Mϩϩ1, 23.2%); H NMR (CDCl3)
d 2.86 (m, 4H, CH2NH), 5.10 (s, 4H, OCH2 pyridine), 5.22
(s, 4H, OCH2 Ar), 6.95–8.08 (m, 21H, ArHs, NH) ppm.
(Calcd for C37H33N3O6 (615.68): C, 72.18; H, 5.40; N,
6.82. Found: C, 72.15; H, 5.32; N, 6.79).
Synthesis of the macrocyclic dithiodiamides 30–33
13,17-Metheno-34H-2,28-di(p-methylphenylazo)-6,12,
18,24,32,33-hexahydrotetrabenzo[b, f,n,r][1,5,17,21,
9,13]tetraoxadiazacyclooctacosin-30,36(31H,35H)-dione
(43). With the use of the general procedure A, the potassium
salt of 26 and 41 gave crude 43 which crystallized from
ethanol as pale yellow crystals (10%), mp 212–214ЊC; IR
(cmϪ1) 3388 (NH), 1651 (CyO); MS (FD): m/z 864 (Mϩ,
General procedure. To a boiling solution of 10–12 and 17
(10 mmol) in toluene (30 ml) was added Lawesson’s
reagent (8.1 g, 20 mmol). The reaction mixture was heated
under reflux for 3 h. After cooling the yellow precipitate
was collected and crystallized from the proper solvent to
give yellow crystals of 30–33, respectively.
1
100%); H NMR (CDCl3) d 1.25 (brs, 2H, CH2CH2NH),
7,11-Nitrilo-2,12,20,21-tetrahydrodibenzo[b, j][1,12,5,8]-
dioxadiazacyclodecin-18,23(19H,22H)-dithione (30).
With the use of the general procedure, 11 gave crude 30
which crystallized from DMF/ethanol as yellow crystals
2.44 (s, 6H, CH3), 3.06 (m, 4H, CH2NH), 5.03 (s, 4H,
OCH2 Ar), 5.28 (s, 4H, OCH2 Ar-azo), 6.97–8.04 (m,
26H, ArHs, NH), 8.73 (m, 2H, NH) ppm. (Calcd for
C53H48N6O6 (864.99): C, 73.59; H, 5.59; N, 9.72. Found:
C, 73.62; H, 5.50; N, 9.81).
1
(72%), mp 241–242ЊC; IR (cmϪ1) 2216 (SH); H NMR
(DMSO) d 4.07 (brs, 4H, NCH2), 5.28 (s, 4H, OCH2),
6.90–7.95 (m, 11H, ArHs, pyridine Hs) 10.38 (brs, 2H,
SH) ppm. (Calcd for C23H21N3O2S2 (435.57): C, 63.42; H,
4.86; N, 9.65; S, 14.72. Found: C, 63.30; H, 5.00; N, 9.90; S,
14.90).
Synthesis of 1,v-bis(2-hydroxy-5-arylazobenzoylamino)-
alkane 26, 27, 29
General procedure. A solution of the appropriate aromatic
amine (10 mmol) in water (5 ml) and conc. HCl (3 ml) was
diazotized at Ϫ5ЊC with a solution of NaNO2 (0.7 g in 5 ml
of water) during 10 min. These diazonium salts were added
dropwise with stirring over a period of 30 min to a cold
(Ϫ5ЊC) solution of the appropriate bis(phenols) 25, 28
(5 mmol) in aqueous NaOH (20 ml, 30%). After the mixture
had been kept overnight in the freezer, acidification with
HCl (3 N) afforded the crude products 26, 27, 29 which
were collected and crystallized from the proper solvent as
orange crystals.
7,11-Nitrilo-22H-6,12,20,21-tetrahydrodibenzo[b,k]-
[1,13,5,9]dioxadiazacycloeicosin-18,24(19H,23H)-
dithione (31). With the use of the general procedure, 13
gave crude 31 which crystallized from toluene as yellow
crystals (70%), mp 236–238ЊC; MS: m/z 449 (Mϩ, 3.5%);
1H NMR (DMSO) d 1.99 (brs, 2H, NCH2CH2), 3.83 (m, 4H,
NCH2), 5.32 (s, 4H, OCH2), 6.99–7.95 (m, 11H, ArHs,
pyridine Hs) 10.42 (brs, 2H, SH) ppm. (Calcd for
C24H23N3O2S2 (449.59): C, 64.12; H, 5.16; N, 9.35; S,
14.26. Found: C, 63.99; H, 5.25; N, 9.28; S, 14.33).
1,3-Bis(2-hydroxy-5-p-methylphenylazobenzoylamino)-
propane (26). With the use of the general procedure,
p-toluidene was diazotized and coupled with 25 to give
crude 26 which crystallized from DMF/ethanol as orange
7,11-Nitrilo-6,12,20,21,22,23-hexahydrodibenzo[b,l]-
[1,14,5,10]dioxadiazacyclohenicosin-18,25(19H,24H)-
dithione (32). With the use of the general procedure, 15
gave crude 32 which crystallized from toluene as yellow
1
1
crystals (60%), mp 264–266ЊC, H NMR (DMSO) d 1.91
crystals (60%), mp 245–246ЊC; H NMR (DMSO) d 1.37

A. H. M. Elwahy, A. A. Abbas / Tetrahedron 56 (2000) 885–895
893
(brs, 4H, NCH2CH2), 3.59 (brs, 4H, NCH2), 5.28 (s, 4H,
OCH2), 6.98–8.06 (m, 11H, ArHs, pyridine Hs) 10.11
(brs, 2H, SH) ppm. (Calcd for C25H25N3O2S2 (463.62): C,
64.77; H, 5.43; N, 9.06; S, 13.83. Found: C, 64.70; H, 5.20;
N, 8.90; S, 13.50).
1,3-Bis[2-(hydroxymethylphenoxy)methyl]benzene (39).
With the use of the general procedure, 37 gave crude 39
which crystallized from toluene as colorless crystals (80%),
mp 95–97ЊC; 1H NMR (CDCl3) d 2.75 (brs, 2H, OH), 4.75
(d, Jˆ5.4 Hz, 4H, CH2OH), 5.16 (s, 4H, OCH2Ar), 6.94–
7.42 (m, 12H, ArHs) ppm. (Calcd for C22H22O4 (350.41): C,
75.41; H, 6.33. Found: C, 75.60; H, 6.60).
7,11-Metheno-2,12,20,21-tetrahydrodibenzo[b, j]-
[1,12,5,8]dioxadiazacyclononadecin-18,23(19H,22H)-
dithione (33). With the use of the general procedure, 17
gave crude 33 which crystallized from DMF/ethanol as
yellow crystals (50%), mp 243–245ЊC; IR (cmϪ1) 2327
Synthesis of bis(chloromethyl) ethers 40 and 41
General procedure. To a cold stirred solution (Ϫ10ЊC) of
each of the diols 38, 39 (10 mmol) in chloroform (100 ml)
was added dropwise thionyl chloride (5 ml). Stirring was
continued for 2 h. The solvent was then removed in vacuo
and the remaining solid was used in next step without
further purification.
1
(SH); H NMR (DMSO) d 4.03 (brs, 4H, NCH2), 5.24
(s, 4H, OCH2), 6.95–7.68 (m, 12H, ArHs) 10.34 (brs, 2H,
SH) ppm. (Calcd for C24H22N2O2S2 (434.58): C, 66.33; H,
5.10; N, 6.45; S, 14.76. Found: C, 66.40; H, 5.30; N, 6.10; S,
14.40).
7,11-Nitrilo-18,23-dimethylthio-2,12,20,21-tetrahydro-
dibenzo[b, j][1,12,5,8]dioxadiazacyclononadecin (34). To
a solution of 30 (5 mmol) in sodium methoxide solution
(prepared from 0.23 g sodium and 20 ml dry methanol)
was added MeI (10 mmol). The reaction mixture was heated
under reflux for 1 h. After cooling and dilution with water
the precipitate was collected and crystallized from DMF to
2,6-Bis[2-(chloromethylphenoxy)methyl]pyridine (40).
With the use of the general procedure, 38 gave 40 as color-
1
less crystals (70%), mp 175–176ЊC; H NMR (CDCl3) d
4.77 (s, 4H CH2Cl), 5.34 (s, 4H, OCH2), 6.94–7.91 (m, 11H,
ArHs) ppm. (Calcd for C21H19Cl2NO2 (388.29): C, 64.96; H,
4.93; N, 3.61; Cl, 18.26. Found: C, 65.20; H, 4.90; N, 3.50;
Cl, 18.31).
1
give colorless crystals of 34 (50%), mp 275–277ЊC; H
NMR (DMSO) d 2.19 (s, 6H, SCH3), 3.58 (s, 4H, NCH2),
5.22 (s, 4H, OCH2), 6.99–7.9 (m, 11H, ArHs) ppm. (Calcd
for C25H25N3O2S2 (463.62): C, 64.77; H, 5.43; N, 9.06; S,
13.83. Found: C, 65.00; H, 5.60; N, 9.20; S, 14.01).
1,3-Bis[2-(chloromethylphenoxy)methyl]benzene (41).
With the use of the general procedure, 39 gave 41 as color-
1
less crystals (75%), mp 110–112ЊC; H NMR (CDCl3) d
4.72 (s, 4H CH2Cl), 5.18 (s, 4H, OCH2), 6.93–7.59 (m, 12H,
ArHs) ppm. (Calcd for C22H20Cl2O2 (387.30): C, 68.23; H,
5.20; Cl, 18.31. Found: C, 68.10; H, 5.40; Cl, 18.60).
7,11-Nitrilo-2,12,20,21-tetrahydrodibenzo[b, j][1,12,5,8]-
dioxadiazacyclononadecin-18,23(19H,22H)-dione-24-
oxide (35). To a solution of each of 11 and 34 (0.5 g) in
acetic acid (5 ml) was added 30% H2O2 (1 ml). The reaction
mixture was heated under reflux for 10 min and allowed to
stand at room temperature overnight. After dilution with
water the precipitate was collected and crystallized from
acetic acid to give colorless crystals of 35 (65 and 60%
yields, respectively) mp 284–286ЊC; MS: m/z 419 (Mϩ,
Synthesis of bis(4-amino-1,2,4-triazol-3-ylsulfanyl)alkanes
53, 54
General procedure. To a solution of each of 45, 46
(50 mmol) in aqueous ethanol (50 ml, 50%) containing
NaOH (2 g, 50 mmol) was added 1,4-dibromobutane
(25 mmol). The reaction mixture was heated under reflux
for 1 h. The solvent was then removed in vacuo and the
remaining solid was collected and crystallized from DMF
to give colorless crystals of compounds 53, 54.
1
5%); H NMR (DMSO) d 3.54 (brs, 4H, NCH2), 5.54 (s,
4H, OCH2), 7.07–8.07 (m, 11H, ArHs pyridine Hs), 9.02
(brs, 2H, NH) ppm. (Calcd for C23H21N3O5 (419.43): C,
65.86; H, 5.08; N, 10.02. Found: C, 65.72; H, 5.12; N, 9.99).
1,4-Bis(4-amino-5-phenyl-1,2,4-triazol-3-ylsulfanyl)-
butane (53). With the use of the general procedure, 45 gave
53 (65%), mp 241–243ЊC; 1H NMR (DMSO) d 1.9 (brs, 4H,
SCH2CH2), 3.24 (brs, 4H, SCH2), 6.12 (s, 4H, NH2), 7.51–
8.03 (m, 10H, ArHs) ppm. (Calcd for C20H22N8S2 (438.58):
C, 54.77; H, 5.06; N, 25.55; S, 14.62. Found: C, 54.70; H,
4.90; N, 25.30; S, 14.30).
Synthesis of bis(hydroxymethyl) ethers 38 and 39
To a stirred solution of the appropriate bis(carbonyl) ethers
36, 37 (10 mmol) in MeOH (10 ml) was added solid NaBH4
(0.89 g, 20 mmol) over a period of 5 min. The reaction
mixture was heated under reflux for 30 min. The solvent
was then removed in vacuo and water 10 ml was added.
The solid obtained was collected and crystallized from the
proper solvent to give 38 and 39.
1,4-Bis(4-amino-5-benzyl-1,2,4-triazol-3-ylsulfanyl)-
butane (54). With the use of the general procedure, 46 gave
1
54 (60%), mp 231–233ЊC; H NMR (DMSO) d 1.79 (brs,
4H, SCH2CH2), 3.12 (brs, 4H, SCH2), 4.01 (s, 4H, CH2Ph),
5.87 (s, 4H, NH2), 7.29 (brs, 10H, ArHs) ppm. (Calcd for
C22H26N8S2 (466.63): C, 65.63; H, 5.62; N, 24.01; S, 13.74.
Found: C, 65.70; H, 5.80; N, 24.20; S, 13.40).
2,6-Bis[2-(hydroxymethylphenoxy)methyl]pyridine (38).
With the use of the general procedure, 36 gave crude 38
which crystallized from methanol as colorless crystals
1
(60%), mp 136–137ЊC; H NMR (CDCl3) d 3.89 (brs, 2H,
OH), 4.75 (d, Jˆ5.4 Hz, 4H, CH2OH), 5.27 (s, 4H,
OCH2Ar), 6.90–7.81 (m, 11H, ArHs) ppm. (Calcd for
C21H21NO4 (351.40): C, 71.78; H, 6.02; N, 3.99. Found:
C, 72.00; H, 6.30; N, 4.10).
2,6-Bis[benzo(b)furan-2-yl]pyridine (55). A solution of 36
(10 mmol) in acetic acid (20 ml) was heated under reflux for
1 h. The solid obtained upon cooling was collected and
crystallized from acetic acid as colorless crystals (50%),

894
A. H. M. Elwahy, A. A. Abbas / Tetrahedron 56 (2000) 885–895
mp 233–235ЊC; MS: m/z 311 (Mϩ, 100%); 1H NMR
(DMSO) d 7.31–8.15 (m, 13H, ArHs pyridin Hs, furan
Hs) ppm. (Calcd for C21H13NO2 (311.34): C, 81.01; H,
4.21; N, 4.50. Found: C, 81.10; H, 4.40; N, 4.20).
With the use of the general procedure, 54 and 37 gave 60
(60%), mp 250–252ЊC; MS (FD): m/z 777 (Mϩ, 100%); 1H
NMR (DMSO) d 1.66 (brs, 4H, SCH2CH2), 3.11 (brs, 4H,
SCH2), 4.22 (s, 4H, CH2Ph), 5.23 (s, 4H, OCH2), 7.05–7.96
(m, 22H, ArHs), 9.12 (s, 2H, CHyN) ppm. (Calcd for
C44H40N8O2S2 (776.98): C, 68.02; H, 4.19; N, 14.42; S,
8.25. Found: C, 68.10; H, 5.30; N, 14.70; S, 8.40).
Synthesis of macrocycles 56–60
General procedure. To a solution of 37 (10 mmol) in
glacial acetic acid (30 ml) was added a solution of the
appropriate bis(4-amino-1,2,4-triazol-3-ylsulfanyl)alkanes
50–54 (10 mmol) in glacial acetic acid (30 mmol). The
reaction mixture was then heated under reflux for 2 h. The
solvent was then removed in vacuo and the remaining solid
was crystallized from acetic acid to give colorless crystals of
56–60.
Action of sodium borohydride on 57–59
General procedure. To a stirred hot (40–50ЊC) solution of
each of 57–59 (0.7 mmol) in methanol (10 ml) was added
sodium borohydride (0.4 g) over a period of 15 min. The
reaction mixture was heated under reflux for 1 h. The
solvent was then removed in vacuo and the remaining
solid was collected, washed with water and crystallized
from methanol to give colorless crystals of 61–63.
13,17-Metheno-12,18,31,32-tetrahydrobis[1,2,4]triazolo-
[4,3-f:3,4-l]dibenzo[b,l][1,18,5,6,13,14,8,11]dioxatetra-
azadithiacyclopentacosine (56). With the use of the
general procedure, 50 and 37 gave 56 (50%), mp 238–
13,17-Metheno-3,27-diphenyl-33H-5,6,12,18,24,25,31,
32-octahydrobis[1,2,4]triazolo[4,3-f:3,4-m]dibenzo-
[b,q][1,19,5,6,14,15,8,12]dioxatetraazadithiacyclohexa-
cosine (61). With the use of the general procedure, 57 gave
61 (70%), mp 182–184ЊC; 1H NMR (CDCl3) d 2.08
(quintet, Jˆ6.6 Hz, 2H, SCH2CH2), 3.09 (t, Jˆ6.4 Hz, 4H,
SCH2), 4.15 (d, Jˆ6.4 Hz, 4H, NHCH2Ar), 5.13 (s, 4H,
OCH2), 5.55 (t, Jˆ6.6 Hz, 2H, NH), 6.85–8.09 (m, 22H,
ArHs) ppm. (Calcd for C41H38N8O2S2 (738.93): C, 66.64;
H, 5.18; N, 15.16; S, 8.68. Found: C, 66.90; H, 5.20; N,
15.30; S, 8.59).
1
240ЊC; H NMR (DMSO) d 3.62 (s, 4H, SCH2), 5.32 (s,
4H, OCH2), 7.06–7.82 (m, 12H, ArHs), 8.92 (s, 2H, CH
triazol), 9.08(s, 2H, CHyN) ppm. (Calcd for
C28H24N8O2S2 (568.68): C, 59.14; H, 4.25; N, 19.70; S,
11.28. Found: C, 59.30; H, 4.10; N, 19.50; S, 11.40).
13,17-Metheno-3,27-diphenyl-33H-12,18,32,33-tetra-
hydrobis[1,2,4]triazolo[4,3-f:3,4-m]dibenzo[b,q]-
[1,19,5,6,14,15,8,12]dioxatetraazadithiacyclohexacosine
(57). With the use of the general procedure, 51 and 37 gave
57 (55%), mp 262–264ЊC; MS (FD): m/z 735 (Mϩ, 100%);
1H NMR (CDCl3) d 2.25 (quintet, Jˆ6.2 Hz, 2H,
SCH2CH2), 3.36 (t, Jˆ6.4 Hz, 4H, SCH2), 5.18 (s, 4H,
OCH2), 7.06–8.08 (m, 22H, ArHs), 9.25 (s, 2H, CHyN)
ppm. (Calcd for C41H34N8O2S2 (734.90): C, 67.01; H,
4.66; N, 15.25; S, 8.73. Found: C, 67.30; H, 4.30; N,
15.10; S, 8.90).
13,17-Metheno-3,27-dibenzyl-33H-5,6,12,18,24,25,31,32-
octahydrobis[1,2,4]triazolo[4,3-f:3,4-m]dibenzo-
[b,q][1,19,5,6,14,15,8,12]dioxatetraazadithiacyclohexa-
cosine (62). With the use of the general procedure, 58 gave
62 (75%), mp 220–222ЊC; IR (cmϪ1) 3182 (NH); 1H NMR
(CDCl3) d 2.0 (quintet, Jˆ6.4 Hz, 2H, SCH2CH2), 3.04 (t,
Jˆ6.8 Hz, 4H, SCH2), 3.84 (d, Jˆ6.2 Hz, 4H, NHCH2Ar),
3.97 (s, 4H, PhCH2), 5.09 (m, 6H, OCH2, NH), 6.93–7.43
(m, 22H, ArHs) ppm; 13C NMR (CDCl3) d 28.45
(SCH2CH2), 30.9 (CH2Ph), 31.36 (SCH2), 51.72 (CHNH),
70.21 (CH2O) 111.89, 121.48, 127.15, 127.24, 127.94,
128.88, 129.08, 130.19, 131.90 (ArCHs), 123.92, 136.14,
136.82, 150.54, 154.74, 157.49 (ArCs) ppm. (Calcd for
C43H42N8O2S2 (766.98): C, 67.34; H, 5.52; N, 14.61; S,
8.36. Found: C, 67.70; H, 5.60; N, 14.34; S, 8.18).
13,17-Metheno-3,27-dibenzyl-33H-12,18,32,33-tetra-
hydrobis[1,2,4]triazolo[4,3-f:3,4-m]dibenzo[b,q]-
[1,19,5,6,14,15,8,12]dioxatetraazadithiacyclohexacosine
(58). With the use of the general procedure, 52 and 37 gave
58 (62%), mp 240–242ЊC; MS (FD): m/z 764 (Mϩϩ1,
1
100%); H NMR (DMSO) d 1.94 (quintet Jˆ6 Hz, 2H,
SCH2CH2), 3.03 (t, Jˆ6.8 Hz, 4H, SCH2), 4.21 (s, 4H,
CH2Ph), 5.19 (s, 4H, OCH2), 7.19–7.94 (m, 22H, ArHs),
9.15 (s, 2H, CHyN) ppm. (Calcd for C43H38N8O2S2
(762.96): C, 67.69; H, 5.02; N, 14.69; S, 8.41. Found: C,
67.70; H, 4.80; N, 14.30; S, 8.60).
13,17-Metheno-3,27-diphenyl-5,6,12,18,24,25,31,32,33,
34-decahydrobis[1,2,4]triazolo[4,3-f:3,4-n]dibenzo-
[b,q][1,20,5,6,15,16,8,13]dioxatetraazadithiacyclohepta-
cosine (63). With the use of the general procedure, 59 gave
63 (65%), mp 185–187ЊC; MS: m/z 752 (Mϩ, 7%); 1H NMR
CDCl3) d 1.76 (brs, 4H, SCH2CH2), 3.11 (brs, 4H, SCH2),
4.14 (d, Jˆ6.4 Hz, 4H, NHCH2), 5.13 (s, 4H, OCH2), 5.50
(t, Jˆ6.6 Hz, 2H, NH), 6.83–8.05 (m, 22H, ArHs) ppm.
(Calcd for C42H40N8O2S2 (752.96): C, 67.00; H, 5.35; N,
14.88; S, 8.52. Found: C, 67.21; H, 5.17; N, 15.00; S, 8.29).
13,17-Metheno-3,27-diphenyl-12,18,31,32,33,34-hexa-
hydrobis[1,2,4]triazolo[4,3-f:3,4-n]dibenzo[b,q][1,20,
5,6,15,16,8,13]dioxatetraazadithiacycloheptacosine (59).
With the use of the general procedure, 53 and 37 gave 59
(55%), mp 265–267ЊC; 1H NMR (DMSO) d 1.73 (brs, 4H,
SCH2CH2), 3.14 (brs, 4H, SCH2), 5.27 (s, 4H, OCH2), 7.11–
7.97 (m, 22H, ArHs), 9.22 (s, 2H, CHyN) ppm. (Calcd for
C42H36N8O2S2 (748.93): C, 67.36; H, 4.84; N, 14.96; S,
8.56. Found: C, 62.50; H, 4.50; N, 15.10; S, 8.40).
References
3,17-Metheno-3,27-dibenzyl-12,18,31,32,33,34-hexa-
hydrobis[1,2,4]triazolo[4,3-f:3,4-n]dibenzo[b,q][1,20,
5,6,15,16,8,13]dioxatetraazadithiacycloheptacosine (60).
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