Synthesis of novel amide-crownophanes and Schiff base-crownophanes based on p-phenylene, 2,6-naphthalene, and 9,10-anthracene

Article abstract of DOI:10.1002/jhet.129

(Chemical Equation Presented) The novel macrocyclic diamides 11-13, 16-18 are obtained in 45-66% yields by the reaction of dipotassium salts 10a-c and 15 with each of 1,4-di(bromomethyl)benzene 4, 2,6-di(bromomethyl)naphthalene 6 and 9,10-di(bromomethyl)anthracene 8, repectively, in boiling DMF. On the other hand, the new macrocyclic Schiff bases 28 and 29 are obtained in 44% and 42% yields by heating the appropriate bis-amines 25b, 26b with the corresponding bis-aldehydes 21, 22, respectively, in refluxing acetic acid under high-dilution conditions.

Full text of DOI:10.1002/jhet.129

656
Synthesis of Novel Amide-Crownophanes and
Schiff Base-Crownophanes Based on p-Phenylene,
2,6-Naphthalene, and 9,10-Anthracene
Vol 46
Hussni A. Muathen,a Nour A. M. Aloweiny,a and Ahmed H. M. Elwahya,b
*
aDepartment of Chemistry, Faculty of Applied Science, Umm Al-Qura University, Makkah
Almukkarramah, Saudi Arabia
bChemistry Department, Faculty of Science, Cairo University, Giza, Egypt
*E-mail: aelwahy@hotmail.com
Received April 8, 2008
DOI 10.1002/jhet.129
Published online 9 July 2009 in Wiley InterScience (www.interscience.wiley.com).
The novel macrocyclic diamides 11–13, 16–18 are obtained in 45–66% yields by the reaction of
dipotassium salts 10a–c and 15 with each of 1,4-di(bromomethyl)benzene 4, 2,6-di(bromomethyl)naph-
thalene 6 and 9,10-di(bromomethyl)anthracene 8, repectively, in boiling DMF. On the other hand, the
new macrocyclic Schiff bases 28 and 29 are obtained in 44% and 42% yields by heating the appropriate
bis-amines 25b, 26b with the corresponding bis-aldehydes 21, 22, respectively, in refluxing acetic acid
under high-dilution conditions.
J. Heterocyclic Chem., 46, 656 (2009).
INTRODUCTION
obtained by simple self-condensation of suitable
formyl- or keto- and primary amine-precursors [18]
and they can be functionalized by inserting appropriate
groups in the aliphatic and/or aromatic chains of the
precursors. They generally can contain additional donor
groups (O, S, P, etc.) and this makes them good candi-
dates for metal ion complexation and for mimicking bi-
ological systems.
Over the past few decades, macrocyclic compounds
have become important synthetic targets due to their
wide applications in host-guest supramolecular chemis-
try. They have been shown to exhibit important appli-
cations, including selective ion separation and detec-
tion, molecular recognition, catalysis, biological appli-
cations as well as many other interesting applications
in diverse fields of supramolecular chemistry [1–8]. In
particular, macrocyclic polyethers with amide groups
in the macrocyclic ring have attracted much attention.
Insertion of these groups into the macrocyclic ring
structure has been reported to affect the binding prop-
erties and selectivity of macrocyclic compounds with
metal cation [9,10] as well as organic molecules [11–
13]. Recently Kumar et al. [14–16] have reported that
diamide-ester macrocyclic compounds showed extraor-
dinary Agþ binding strength with a remarkable selec-
tivity for Ag over other metal ions. Macrocyclic
amides are also precursors in the preparation of aza-
crown ethers and cryptands [4,6,9,11]. Furthermore,
some diamide-containing macrocycles have been uti-
lized as new catalysts [17]. Moreover, a progressive in-
terest was directed in the last few years to the synthesis
of novel macrocyclic Schiff bases because they can be
Furthermore, considerable attention has been focused
on crown ethers bearing chromophores such as naphtha-
lene and/or anthracene. They are promising analytical
reagents for colorimetry and can be used for spectropho-
tometric determination of metal ions [19]. Anthracene is
one of the most employed chromophores due to its abil-
ity to induce PET (photoinduced electron transfer) proc-
esses [20]. The naphthalene moiety is also a well-known
fluorophore and its ability to block intersystem crossing
in the first excited state is remarkable [21]. The detec-
tion of metal ions with a high specificity under physio-
logically relevant conditions is an important issue in the
design of fluorescent chemosensors in biological and
environmental applications [22].
We have investigated several synthetic approaches
towards macrocyclic azacrown compounds where some
of them showed useful application in ion selective elec-
trodes and as spectrophotometric reagents [23].
C
V
2009 HeteroCorporation

July 2009
Synthesis of Novel Amide-Crownophanes and Schiff
Base-Crownophanes Based on p-Phenylene, 2,6-Naphthalene, and 9,10-Anthracene
657
Although up to now, many kinds of azacrownophanes
were prepared, development of a mild and effective syn-
thetic route to this type of macrocycles still remains an
attractive and challenging subject for synthetic chemists.
Here, we report on the synthesis of a new family of am-
ide-crownophanes and Schiff base-crownophanes that
use p-phenylene, 2,6-naphthalene or 9,10-anthracene as
assembling units.
RESULTS AND DISCUSSION
Previously, we reported the synthesis of tribenzo- and
tetra-benzosubstituted macrocyclic diamides 1 and their
corresponding azo derivatives 2, in which the arylazo
groups act as chromophoric side arms, by the reaction
of the potassium salts of the appropriate bis(phenols)
with the corresponding dihalo compounds in refluxing
DMF [23a,b,f,h].
In this study, we intended to insert the chromo-
phoric units 2,6-naphthalene and 9,10-anthracene into
the macrocyclic rings 1. The insertion of p-phenylene
unit into the macrocycles 1 was also investigated for a
comparison study. For this purpose, the bis(bromo-
methyl) compounds 4, 6, and 8 were chosen as a key
intermediate and could be readily obtained from the
corresponding dimethyl derivatives 3, 5, and 7, respec-
tively, by bromination with Br2 or N-bromosuccini-
mide (NBS) in CCl4 according to reported methods
[24] (Scheme 1).
tions give the corresponding macrocyclic diamides 16–
18 in 49–62% yields, respectively (Scheme 3).
Our study was extended to include the insertion of
chromophoric units into the macrocyclic Schiff base 19.
The latter compounds were recently obtained by cyclo-
condensation of the appropriate bis(carbonyl) ethers
with the corresponding bis(amines) in glacial acetic acid
under high-dilution conditions [23(f,l)].
To achieve this goal, the novel bis(aldehyde)s 21–23
as well as the novel bis(amine)s 25–27 were prepared as
outlined in Schemes 4 and 5. Compounds 4, 6, and 8
serve as starting materials for the synthesis of 21–23,
25–27. Thus, reaction of 4, 6, and 8 with the potassium
salt 20 (obtained upon treatment of salicylaldehyde with
ethanolic potassium hydroxide) in refluxing DMF
afforded the corresponding bis(aldehydes) 21–23 in 65–
80% yield (Scheme 4).
Thus, the treatment of the bis(phenol)s 9 with etha-
nolic KOH afforded the corresponding dipotassium
salt 10. Alkylation of 10 with 4, 6, and 8 in boiling
DMF led to the formation of the novel macrocyclic
diamides 11–13 in 45–66% yield (Scheme 2). It is
noteworthy that we were not able to isolate pure sam-
ple of 13a by the reaction of 10a with 8 under similar
conditions.
On the other hand, reaction of 4, 6 and 8 with 4-
amino-1,2,4-triazol-3-thiones 24a,b in ethanol/water
mixture containing potassium hydroxide afforded the
corresponding bis(4-amino-1,2,4-triazol-3-ylsulfanylme-
thyl)arenes 25–27 in 67–81% yield (Scheme 5).
The synthetic utility of the novel bis(aldehyde)s 21–
23 and the bis(amine)s 25–27 as building blocks for
novel macrocyclic Schiff bases containing p-phenylene,
2,6-naphthalene, or 9,10-anthracene groups incorporated
into the ring system was then investigated. Thus, cyclo-
condensation of 21 with 1,4-bis(4-amino-5-phenyl-3-
We also studied the insertion of an additional 1,3-
xyly unit into the macrocyclic ring 11–13 instead of the
alkylene moieties, aiming at studying the effect of rigid-
ity provided by these groups on the ability of the ligands
to form stable complexes compared with other macrocy-
clic analogues. Thus, reacting the dipotassium salts 15
(obtained from the corresponding bis(phenol) 14 upon
treatment with ethanolic KOH) with the corresponding
bis(bromomethyl)arenes 4, 6, and 8 under similar condi-
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

658
H. A. Muathen, N. A. M. Aloweiny, and A. H. M. Elwahy
Vol 46
Scheme 1
ylsulfanylmethyl)benzene (25b) in glacial acetic acid
under high-dilution conditions gave the corresponding
macrocyclic Schiff base 28 in 44% yield. Under similar
conditions 22 reacted with 26b to give the corresponding
macrocyclic Schiff base 29 in 42% yield (Scheme 6).
Unfortunately repeated attempts to react 9,10-bis(2-for-
mylphenoxymethyl)anthracene 23 with with 9,10-bis(4-
amino-5-phenyl-3-ylsulfanylmethyl)anthracene 27b in
refluxing acetic acid under high dilution conditions did
not lead to the formation of the expected macrocyclic
Schiff base 30. Instead, the reaction gave 55% of another
successfully as key intermediates for the synthesis of
novel macrocyclic Schiff bases upon which fused tria-
zole units and contain N, O, and S inside the macrocy-
clic ring as donor atoms. We also prepared a new series
of amide-crownophanes by the reaction of the appropri-
ate bis(phenol)s with the corresponding dihalo com-
pounds. The novel macrocycles use p-phenylene, 2,6-
naphthalene or 9,10-anthracene as assembling units.
Some derivatives of the new dilactams as well as the
new Schiff bases showed promising cation binding prop-
erties in a preliminary spectrophotometric study. This
data will be published separately due to the large quan-
tity of analytical data accumulated.
1
product which was characterized by H NMR (DMSO),
IR, and mass spectra as 9,10-bis(acetyloxymethyl)-anthra-
cene 31. The latter was obtained in 50% yield by heating
only 23 in refluxing acetic acid (Scheme 7).
In conclusion, we prepared a new series of bis(4-
amino-1,2,4-triazol-3-ylsulfanylmethyl)arenes as well as
bis(2-formylphenoxymethyl)arenes and utilized them
EXPERIMENTAL
Melting points are uncorrected. IR spectra (KBr) were
recorded on a Perkin-Elmer 1430 spectrophotometer. NMR
Scheme 2
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July 2009
Synthesis of Novel Amide-Crownophanes and Schiff
Base-Crownophanes Based on p-Phenylene, 2,6-Naphthalene, and 9,10-Anthracene
659
Scheme 3
Scheme 4
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660
H. A. Muathen, N. A. M. Aloweiny, and A. H. M. Elwahy
Vol 46
Scheme 5
spectra were measured with a Varian Mercury 300 (300 MHz
1H NMR, 75 MHz 13C NMR) spectrophotometer and chemical
shifts are given in ppm from TMS. Mass spectra were
recorded on GC MS-QP1000 EX (70 eV) or MS 5988 (15 eV)
spectrometers. Elemental analyses were carried out at the
Microanalytical Centre, Cairo University. 4-Aminotriazol-3-
thione derivatives 24a,b were prepared as reported [25].
Preparation of dipotassium salts 10, 15, general proce-
dure [28a,28s,28y]. To a solution of KOH (1.14 g, 10 mmol)
in methanol (10 mL) was added the appropriate bis(phenol)
9a–c, 14 (5 mmol). The mixture was stirred at room tempera-
ture for 10 min. The solvent was then removed in vacuo. The
remaining solid was triturated with dry ether, collected, dried,
and used in the next step without further purification.
Synthesis of macrocycles 11a–c, 12a–c, 13b,c, 16–18, gen-
eral procedure. A solution of the appropriate potassium salt
10a–c, 15 (10 mmol) and the appropriate dihalo compound 4,
6, 8 (10 mmol) in DMF (20 mL) was heated under reflux for
10 min. during which time KCl precipitated. The solvent was
then removed in vacuo and the remaining material was washed
with water (50 mL) and purified by crystallization from acetic
acid unless otherwise noted.
Macrocycle 11a. Reaction of 10a with 4 produced 11a as
colorless crystals (64%), mp 253–254ꢀC; IR: 3376 (NH), 1651
(C¼¼O) cmꢁ1
;
1H NMR (DMSO-d6) d 3.26 (s, 4H, CH2NH),
5.20 (s, 4H, OCH2), 7.02–7.57 (m, 14H, ArH’s, NH); 13C
NMR (DMSO) d 38.66 (CH2N), 72.48 (OCH2), 116.51,
121.49, 125.72, 129.35, 129.86, 131.90, 136.60, 155.77
(ArC’s), 165.28 (C¼¼O); MS (EI): m/z 402 (Mþ, 2%), 282
(42.6%), 239 (15.1%), 162 (24.5%), 104 (100%). Anal. Calcd.
for C24H22O4N2 (402.45): C, 71.63; H, 5.51; N, 6.96. Found:
C, 71.80; H, 5.30; N, 7.20.
Macrocycle 11b. Reaction of 10b with 4 produced 11b as
colorless crystals (62%), mp > 300ꢀC; IR: 3376 (NH), 1648
(C¼¼O) cmꢁ1
; d 1.06 (m, 2H,
1H NMR (DMSO-d6)
CH2CH2NH), 3.04 (m, 4H, CH2NH), 5.17 (s, 4H, OCH2),
7.06–7.83 (m, 14H, ArH’s, NH); 13C NMR (DMSO) d 29.10
(CH2CH2NH), 37.20 (CH2N), 71.20 (OCH2), 109.26, 113.06,
120.86, 130.07, 130.32, 132.26, 136.50, 155.80 (ArC’s),
164.30 (C¼¼O); MS (EI): m/z 416 (Mþ, 2.7%), 296 (47.8%),
Scheme 6
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DOI 10.1002/jhet

July 2009
Synthesis of Novel Amide-Crownophanes and Schiff
Base-Crownophanes Based on p-Phenylene, 2,6-Naphthalene, and 9,10-Anthracene
661
Scheme 7
(24.4%). Anal. Calcd. for C30H28O4N2 (480.57): C, 74.98; H,
5.87; N, 5.83. Found: C, 74.80; H, 5.50; N, 5.70.
Macrocycle 13b. Reaction of 10b with 8 produced 13b as
yellow crystals (45%), mp 291–292ꢀC; IR: 3388, 3421 (NH),
1640 (C¼¼O) cmꢁ1
;
1H NMR (DMSO-d6) d ꢁ0.34 (brs, 2H,
CH2CH2NH), 2.64 (m, 4H, CH2NH), 6.37 (s, 4H, OCH2),
7.14–8.52 (m, 18H, ArH’s, NH); 13C NMR (DMSO) d 26.24
(CH2CH2NH), 36.41 (CH2N), 64.23 (OCH2), 113.74, 120.71,
121.20, 124.77, 126.65, 129.14, 130.04, 130.54, 132.54,
156.74 (ArC’s), 163.56 (C¼¼O); MS (EI): m/z 516 (Mþ,
45.5%), 396 (100%), 314 (13.8%), 204 (81.1%), 178 (86.8%),
121 (73.5). Anal. Calcd. for C33H28O4N2 (516.60): C, 76.73;
H, 5.46; N, 5.42. Found: C, 76.80; H, 5.30; N, 5.20.
Macrocycle 13c. Reaction of 10c with 8 produced 13c as
yellow crystals (51%), mp 259–260ꢀC; IR: 3402 (NH), 1650
(C¼¼O) cmꢁ1
; d 0.28 (s, 4H,
1H NMR (DMSO-d6)
CH2CH2NH), 2.73 (m, 4H, CH2NH), 6.30 (s, 4H, OCH2),
7.14–8.50 (m, 18H, ArH’s, NH). 13C NMR (DMSO) d 25.92
(CH2CH2NH), 37.10 (CH2N), 63.19 (OCH2), 113.88, 121.28,
124.68, 126.69, 128.95, 130.03, 131.13, 132.76, 156.78
(ArC’s), 163.66 (C¼¼O); MS (EI): m/z 530 (Mþ, 14.9%), 410
(56.8%), 204 (75.6%), 121(100%). Anal. Calcd. for
C34H30O4N2 (530.63): C, 76.96; H, 5.70; N, 5.28. Found: C,
76.80; H, 5.40; N, 5.20.
178 (16.3%), 104 (100%). Anal. Calcd. for C25H24O4N2
(416.48): C, 72.10; H, 5.81; N, 6.73. Found: C, 72.30; H,
5.70; N, 6.70.
Macrocycle 11c. Reaction of 10c with 4 produced 11c as
colorless crystals (61%), mp 291–292ꢀC; IR: 3413, 3380
Macrocycle 16. Reaction of 15 with 4 produced 16 as color-
less crystals [acetic acid-ethanol (1:1)] (62%), mp 281–282ꢀC;
1
(NH), 1647 (C¼¼O) cmꢁ1; H NMR (DMSO-d6) d 1.21 (s, 4H,
CH2CH2NH), 3.19 (m, 4H, CH2NH), 5.21 (s, 4H, OCH2),
7.07–7.91 (m, 14H, ArH’s, NH); 13C NMR (DMSO) d 26.87
(CH2CH2NH), 38.82 (CH2N), 70.87 (OCH2), 113.22, 120.93,
122.35, 130.88, 132.43, 136.39, 156.54 (ArC’s), 164.21
(C¼¼O); MS (EI): m/z 430 (Mþ, 1.6%), 310 (49.4%), 173
(25.3%), 104 (100%). Anal. Calcd. for C26H26O4N2 (430.51):
C, 72.54; H, 6.09; N, 6.51. Found: C, 72.70; H, 5.90; N, 6.20.
Macrocycle 12a. Reaction of 10a with 6 produced 12a as
colorless crystals (54%), mp 197–199ꢀC; IR: 3390 (NH), 1636
IR: 3392 (NH), 1648 (C¼¼O) cmꢁ1
;
1H NMR (DMSO-d6) d
4.46 (m, 4H, CH2NH), 5.15 (s, 4H, OCH2), 7.09–7.93 (m,
16H, ArH’s), 8.48 (br, 2H, NH); MS (EI): m/z 478 (Mþ,
5.9%), 358 (25.7%), 254 (10.6%), 121 (55.9%), 104 (100%).
Anal. Calcd. for C30H26N2O4 (478.55): C, 75.30; H, 5.48; N,
5.85. Found: C, 75.40; H, 5.70; N, 5.90.
Macrocycle 17. Reaction of 15 with 6 produced 17 as color-
less crystals (ethanol) (49%), mp 258–259ꢀC; IR: 3391 (NH),
1649 (C¼¼O) cmꢁ1
;
1H NMR (DMSO-d6) d 4.32 (m, 4H,
1
(C¼¼O) cmꢁ1; H NMR (DMSO-d6) d 3.47 (m, 4H, CH2NH),
CH2NH), 5.31 (s, 4H, OCH2), 6.50–7.97 (m, 18H, ArH’s),
8.17 (br, 2H, NH); 13C NMR (DMSO) d 42.59 (CH2N), 71.27
(OCH2), 113.10, 120.96, 121.99, 123.36, 125.66, 126.87,
127.67, 128.19, 130.83, 132.55, 132.68, 133.33, 136.85,
156.74 (ArC’s), 164.51 (C¼¼O); MS (EI): m/z 528 (Mþ, 9.4%),
408 (49.1%), 339 (25.7%), 288 (22%), 154 (100). Anal. Calcd.
for C34H28N2O4 (528.61): C, 77.26; H, 5.34; N, 5.30. Found:
C, 77.30; H, 5.30; N, 4.90.
5.32 (m, 4H, OCH2), 7.33–7.84 (m, 14H, ArH’s), 8.40 (brs,
2H, NH); MS (EI): m/z 453 (Mþþ1, 2.5%), 369 (2.6%), 300
(17.5%), 247 (13.6%), 155 (4.2%). Anal. Calcd. for
C28H24O4N2 (452.51): C, 74.32; H, 5.35; N, 6.19. Found: C,
74.50; H, 5.30; N, 6.20.
Macrocycle 12b. Reaction of 10b with 6 produced 12b as
colorless crystals (66%), mp 287–289ꢀC; IR: 3384 (NH), 1641
(C¼¼O) cmꢁ1
;
1H NMR (DMSO-d6)
d
0.13 (m, 2H,
Macrocycle 18. Reaction 15 with 8 produced 18 as yellow
crystals [acetic acid-ethanol (1:1)] (51%), mp 245–246ꢀC; IR:
CH2CH2NH), 2.79 (brs, 4H, CH2NH), 5.38 (s, 4H, OCH2),
7.03–8.16 (m, 16H, ArH’s, NH); 13C NMR (DMSO) d 26.40
(CH2CH2NH), 37.28 (CH2N), 73.26 (OCH2), 114.93, 121.30,
122.32, 127.71, 128.66, 128.96, 130.82, 132.75, 133.20,
134.35, 156.96 (ArC’s), 163.84 (C¼¼O); MS (EI): m/z 466
(Mþ, 15.6%), 346 (93.9%), 154 (100%), 121 (36.9%). Anal.
Calcd. for C29H26O4N2 (466.54): C, 74.66; H, 5.62; N, 6.01.
Found: C, 74.80; H, 5.30; N, 5.80.
1
3485, 3389 (NH), 1641 (C¼¼O) cmꢁ1; H NMR (DMSO-d6) d
3.91 (m, 4H, CH2NH), 6.18 (s, 4H, OCH2), 6.50–8.39 (m,
20H, ArH’s, NH); MS (EI): m/z 578 (Mþ, 9.4%), 458 (13.7%),
338 (11.5%), 240 (17.6%), 205 (100%), 121 (51.5%). Anal.
Calcd. for C38H30N2O4 (578.67): C, 78.87; H, 5.23; N, 4.84.
Found: C, 78.80; H, 4.90; N, 4.90.
Synthesis of bis(aldehyde)s 21–23, general procedure. A
solution of the potassium salt of salicylaldehyde 20 (20 mmol)
and the dibromo compound 4, 6, 8 (10 mmol) in DMF (20
mL) was heated under reflux for 5 min. during which the po-
tassium chloride precipitated. The solution was concentrated to
small volume (ca. 2 mL) and then cold water (ca. 10 mL) was
added. The solid obtained was collected and crystallized from
acetic acid.
Macrocycle 12c. Reaction of 10c with 6 produced 12c as
colorless crystals (61%), mp 254–255ꢀC; IR: 3426, 3385
(NH), 1642 (C¼¼O) cmꢁ1
;
1H NMR (DMSO-d6) d 0.68 (brs,
4H, CH2CH2NH), 2.85 (m, 4H, CH2NH), 5.38 (s, 4H, OCH2),
7.05–8.12 (m, 16H, ArH’s, NH); 13C NMR (DMSO) d 26.76
(CH2CH2NH), 38.80 (CH2N), 72.73 (OCH2), 115.19, 121.10,
121.34, 123.76, 127.54, 128.56, 130.40, 132.27, 132.94,
134.42, 156.49 (ArC’s), 164.35 (C¼¼O); MS (EI): m/z 480
(Mþ, 11.1%), 360 (100%), 223 (19.2%), 154 (55.7%), 121
1,4-Bis(2-formylphenoxymethyl)benzene (21). Reaction of
20 with 4 produced 21 as colorless crystals (80%), mp 189–
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H. A. Muathen, N. A. M. Aloweiny, and A. H. M. Elwahy
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190ꢀC; IR: 2762, 2850 (CHO), 1686 (C¼¼O) cmꢁ1
;
1H NMR
155 (29.2%), 116 (100%). Anal. Calcd. for C16H16N8S2
(384.49): C, 49.98; H, 4.19; N, 29.14. Found: C, 50.10; H,
4.30; N, 28.90.
(DMSO-d6) d 5.30 (s, 4H, OCH2), 7.06–7.73 (m, 12H, ArH’s),
10.44 (s, 2H, CHO); 13C NMR (DMSO) d 69.77 (OCH2),
114.15, 120.93, 124.73, 127.64, 127.86, 136.15, 136.22,
160.51 (ArC’s), 189.05 (C¼¼O); MS (EI): m/z 346 (Mþ, 0.1%),
224 (38%), 179 (4.6%), 121.05 (11.7%), 104 (92.2%), 91
(100%). Anal. Calcd. for C22H18O4 (346.38): C, 76.29; H,
5.24. Found: C, 76.30; H, 4.90.
2,6-Bis(4-amino-5-phenyl-1,2,4-triazol-3-ylsulfanylmethyl)-
naphthalene (26b). Reaction of 24b with 6 gave 26b as color-
less crystals (acetic acid) (74%), mp 240–241ꢀC; IR: 3315,
1
3183 (NH2) cmꢁ1; H NMR (DMSO-d6) d 4.60 (s, 4H, SCH2),
6.10 (s, 4H, NH2), 7.48–7.98 (m, 16H, ArH’s); 13C NMR
(DMSO-d6) d 35.33 (SCH2), 120.71, 126.81, 127.29, 127.57,
127.86, 128.41, 129.57, 131.91, 135.17, 152.91, 154.03
(ArC’s, Triazole C’s). Anal. Calcd. for C28H24N8S2 (536.69):
C, 62.66; H, 4.51; N, 20.88. Found: C, 62.40; H, 4.30; N,
21.00.
2,6-Bis(2-formylphenoxymethyl)naphthalene (22). Reaction
of 20 with 6 produced 22 as colorless crystals (65ꢁ%1), mp 191–
192ꢀC; IR: 2761, 2868 (CHO), 1674 (C¼¼O) cm
;
1H NMR
(DMSO-d6) d 5.45 (s, 4H, OCH2), 7.07–8.05 (m, 14H, ArH’s),
10.49 (s, 2H, CHO); 13C NMR (DMSO) d 69.98 (OCH2),
114.13, 120.59, 120.63, 120.95, 125.84, 126.07, 127.83,
128.27, 134.33, 136.27, 160.53 (ArC’s), 189.25 (C¼¼O); MS
(EI): m/z 396 (Mþ, 0.9%), 275 (55.9%), 215 (0.9%), 169
(2.2%), 154 (100%). Anal. Calcd. for C26H20O4 (396.45): C,
78.77; H, 5.09. Found: C, 78.70; H, 4.90.
9,10-Bis(4-amino-1,2,4-triazol-3-ylsulfanylmethyl)anthracene
(27a). Reaction of 24a with 8 produced 27a as yellow crystals
(DMF/H2O) (67%), mp 243–244ꢀC; IR: 3332, 3281 (NH2)
1
cmꢁ1; H NMR (DMSO-d6) d 5.46 (s, 4H, SCH2), 6.14 (s, 4H,
NH2), 7.64–8.47 (m, 8H, ArH’s), 8.55 (s, 2H, triazole H’s);
13C NMR (DMSO-d6) d 29.40 (SCH2), 124.79, 126.39,
128.90, 129.35, 146.39, 150.45 (ArC’s, Triazole C’s); MS
(EI): m/z 434 (Mþ, 2.2%), 318 (5.7%), 204 (18.2%), 116
(100%). Anal. Calcd. for C20H18N8S2 (434.55): C, 55.28; H,
4.18; N, 25.79. Found: C, 55.30; H, 4.30; N, 25.90.
9,10-Bis(2-formylphenoxymethyl)anthracene (23). Reaction
of 20 with 8 produced 23 as yellow crystals (DMF) (70%), mp
248–249ꢀC; IR: 2753, 2850 (CHO), 1682 (C¼¼O) cmꢁ1
;
1H
NMR (DMSO-d6) d 6.28 (s, 4H, OCH2), 7.14–8.51 (m, 16H,
ArH’s), 10.04 (s, 2H, CHO); MS (EI): m/z 446 (Mþ, 2.5%),
325 (26%), 204 (100%), 121 (35.6%). Anal. Calcd for
C30H22O4 (446.51): C, 80.70; H, 4.97. Found: C, 80.60; H,
5.10.
9,10-Bis(4-amino-5-phenyl-1,2,4-triazol-3-ylsulfanylmethyl)-
anthracene (27b). Reaction of 24b with 8 produced 27b as
yellow crystals (DMF/H2O) (75%), mp 233–235ꢀC; IR: 3281,
1
Synthesis of bis(amine)s 25a,b–27a,b, general procedure.
To a solution of 24a, b (50 mmol) in aqueous ethanol (50 mL,
50%) containing KOH (50 mmol) was added the appropriate
dibromo compound 4, 6, 8 (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 crystal-
lized from the proper solvent.
3353 (NH2) cmꢁ1; H NMR (DMSO-d6) d 5.52 (s, 4H, SCH2),
6.17 (s, 4H, NH2), 7.53–8.52 (m, 18H, ArH’s); MS (EI): m/z
586 (Mþ, 9%), 394 (46.1%), 228 (25.8%), 192 (82%), 104
(100%). Anal. Calcd. for C32H26N8S2 (586.75): C, 65.51; H,
4.47; N, 19.10. Found: C, 65.30; H, 4.30; N, 18.90.
Synthesis of macrocyclic bis-Schiff bases 28, 29,
and 9,10-bis(acetyloxymethyl)-anthracene 31, general
procedure. To a solution of the appropriate bis aldehyde 21–
23 (10 mmol) in glacial acetic acid (50 mL) was added a solu-
tion of the appropriate bis amine 25b, 26b, 27b (10 mmol) in
glacial acetic acid (50 mL). The reaction mixture was then
heated under reflux for 2 h. The solution was concentrated to
small volume (ca. 2 mL) and then cold water (ca. 15 mL) was
added. The precipitate obtained was collected and recrystal-
lized from acetic acid.
1,4-Bis(4-amino-1,2,4-triazol-3-ylsulfanylmethyl)benzene (25a).
Reaction of 24a with 4 produced 25a as colorless crystals
(DMF/H2O) (71%), mp 207–209ꢀC; IR: 3333, 3092 (NH2)
1
cmꢁ1; H NMR (DMSO-d6) d 4.35 (s, 4H, SCH2), 6.02 (s, 4H,
NH2), 7.33 (s, 4H, ArH’s), 8.44 (s, 2H, triazole H’s); 13C
NMR (DMSO-d6) d 34.73 (SCH2), 128.95, 136.60, 146.19,
150.47 (ArC’s, Triazole C’s); MS (EI): m/z 334 (Mþ, 0.4%),
218 (3.9%), 203 (8%), 183 (4%), 128 (4.9%), 116 (100%).
Anal. Calcd. for C12H14N8S2 (334.43): C, 43.10; H, 4.22; N,
33.51. Found: C, 43.40; H, 4.30; N, 33.50.
Macrocycle 28. Reaction of 21 with 25b produced 28 as
1
colorless crystals (44%), mp 248–249ꢀC; H NMR (DMSO-d6)
1,4-Bis(4-amino-5-phenyl-1,2,4-triazol-3-ylsulfanylmethyl)-
benzene (25b). Reaction of 24b with 4 produced 25b as color-
less crystals (dilute acetic acid) (81%), mp 214–215ꢀC; IR:
d 4.43 (s, 4H, SCH2), 5.24 (s, 4H, OCH2), 7.14–7.99 (m, 26H,
ArH’s), 9.18 (s, 2H, CH¼¼N). MS (EI): m/z 796 (Mþ, 0.4%),
626 (0.3%), 561 (0.8%), 558 (0.8%), 486 (1.6%), 280 (22.4%),
222 (76.5%), 177 (24.9%), 104 (100%). Anal. Calcd. for
C46H36N8O2S2 (796.98): C, 69.33; H, 4.55; N, 14.06. Found:
C, 69.40; H, 4.30; N, 14.30.
1
3309, 3181 (NH2) cmꢁ1; H NMR (DMSO-d6) d 4.42 (s, 4H,
SCH2), 6.09 (s, 4H, NH2), 7.42–7.99 (m, 14H, ArH’s); 13C
NMR (DMSO-d6) d 34.93 (SCH2), 126.85, 127.72, 128.37,
129.03, 129.54, 136.63, 152.85, 154.02 (ArC’s, Triazole C’s);
MS (EI): m/z 486 (Mþ, 2.6%), 294 (11.8%), 192 (100%), 121
(20.1%). Anal. Calcd. for C24H22N8S2 (486.63): C, 59.24; H,
4.56; N, 23.03. Found: C, 59.30; H, 4.30; N, 22.90.
Macrocycle 29. Reaction of 22 with 26b gave 29 as color-
less crystals (42%), mp 254–255ꢀC; 1H NMR (DMSO-d6) d
4.60 (s, 4H, SCH2), 5.38 (s, 4H, OCH2), 7.17–8.03 (m, 30H,
ArH’s), 9.21 (s, 2H, CH¼¼N). MS (EI): m/z 896 (Mþ, 0.5%),
522 (0.9%), 448 (1.6%), 390 (2.1%), 330 (4%), 272 (65.5%),
154 (100%). Anal. Calcd. for C54H40N8O2S2 (897.10): C,
72.30; H, 4.49; N, 12.49. Found: C, 72.40; H, 4.30; N, 12.20.
9,10-Bis(acetyloxymethyl)anthracene (31). Reaction of 23
with 27b produced 31 as yellow crystals (55ꢁ%1), mp 214–
2,6-Bis(4-amino-1,2,4-triazol-3-ylsulfanylmethyl)naphthalene
(26a). Reaction of 24a with 6 produced 26a as colorless crys-
tals (DMF/H2O) (69%), mp 216–217ꢀC; IR: 3325, 3109 (NH2)
1
cmꢁ1; H NMR (DMSO-d6) d 4.53 (s, 4H, SCH2), 6.04 (s, 4H,
NH2), 7.53–7.86 (m, 6H, ArH’s), 8.44 (s, 2H, triazole H’s);
13C NMR (DMSO-d6) d 35.68 (SCH2), 120.81, 127.15,
127.44, 127.80, 131.94, 135.14, 146.10 (ArC’s, Triazole C’s);
MS (EI): m/z 385 (Mþþ1, 3.2%), 327 (2.6%), 268 (21.7%),
215ꢀC; 178 (35.29%); IR: 1729 (C¼¼O) cm
;
1H NMR
(DMSO-d6) d 2.02 (s, 6H, OCOCH3), 6.15 (s, 4H, OCH2),
7.65–8.45 (m, 8H, ArH’s); MS (EI): m/z 322 (Mþ, 30.71%),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

July 2009
Synthesis of Novel Amide-Crownophanes and Schiff
Base-Crownophanes Based on p-Phenylene, 2,6-Naphthalene, and 9,10-Anthracene
663
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet