Synthesis of a new class of azathia crown macrocycles containing two 1,2,4-triazole or two 1,3,4-thiadiazole rings as subunits

Article abstract of DOI:10.1016/j.tetlet.2008.12.014

A series of new 1,2/1,3-bis[o-(N-methylidenamino-5-aryl-3-thiol-4H-1,2,4-triazole-4-yl)p henoxy]alkane derivatives 3a-d and bis[o-(N-methylidenamino-2-thiol-1,3,4-thiadiazole-5-yl)phenoxy]alkanes 6a-c were prepared by condensation of 4-amino-5-(aroyl)-4H-

Full text of DOI:10.1016/j.tetlet.2008.12.014

Tetrahedron Letters 50 (2009) 836–839
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Tetrahedron Letters
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Synthesis of a new class of azathia crown macrocycles containing two
1,2,4-triazole or two 1,3,4-thiadiazole rings as subunits
*
Naser Foroughifar , Akbar Mobinikhaledi, Sattar Ebrahimi, Hassan Moghanian,
Mohammad Ali Bodaghi Fard, Mehdi Kalhor
Department of Chemistry, Faculty of Sciences, Arak University, Arak 38156-879, Iran
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of new 1,2/1,3-bis[o-(N-methylidenamino-5-aryl-3-thiol-4H-1,2,4-triazole-4-yl)phenoxy]alkane
derivatives 3a–d and bis[o-(N-methylidenamino-2-thiol-1,3,4-thiadiazole-5-yl)phenoxy]alkanes 6a–c
were prepared by condensation of 4-amino-5-(aroyl)-4H-1,2,4-triazole-3-thiols 2a–b or 2-amino-5-mer-
capto-1,3,4-thiadiazole with bis-aldehydes 1a–c. Further reaction of compounds 3a–d and 6a–c with dib-
romoalkanes afforded the new macrocycles 5a–f and 8a–d. The cyclization does not require high dilution
techniques and provides the expected azathia macrocycles in good yields, ranging from 55% to 68%.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 4 August 2008
Revised 26 November 2008
Accepted 3 December 2008
Available online 7 December 2008
Keywords:
Azathia crown
Schiff base
1,2,4-Triazole
1,3,4-Thiadiazole
1. Introduction
of fields.12 These macrocycles were found to exhibit interesting
host–guest complexation characteristics,14 and have shown anti-
Recently, much attention has been focused on 1,2,4-triazole and
1,3,4-thiadiazole derivatives due to their broad-spectrum activities
such as antitumor, analgesic, anticancer, anti-inflammatory, and
antibacterial activities.1–5 Schiff base derivatives of 1,2,4-triazoles
and their reduced derivatives have also been found to possess
pharmacological activities.6–8
bacterial activities,15 in which the biological activity is highly
dependent upon the side chain substitution pattern. These proper-
ties prompted us to synthesize some new bis-Schiff-base deriva-
tives and a series of 20–24-membered macrocycles fused with
two 1,2,4-triazole or two 1,3,4-thiadiazole rings.
Recently, Abbas16 reported the synthesis of azathia crown
ethers by reacting a bis-triazole with a bis-aldehyde in acetic acid
under high dilution conditions (the high dilution technique is the
most versatile procedure for the synthesis of macrocycles17). On
the other hand, Sharghi18 and others19–22 reported the synthesis
of macrocycles without the use of high dilution techniques. In this
Letter, we demonstrate a new method to introduce 1,2,4-triazole
or 1,3,4-thiadiazole rings into macrocycles employing novel pre-
cursors 3 and 6 (Schemes 1 and 2) without using high dilution
conditions.
The macrocyclization step in this method involves the reaction
of bis[o-(N-methylidenamino-5-aryl-3-thiol-4H-1,2,4-triazole-4-
yl)phenoxy]alkane derivatives 3a–d or bis[o-(N-methylidenami-
no-2-thiol-1,3,4-thiadiazole-5-yl)phenoxy]alkanes 6a–c with the
appropriate dibromoalkanes as shown in Schemes 1 and 2. Two
strategies were attempted for the synthesis of macrocycles 5a–f.
In the first strategy, bis-triazoles were chosen as the starting mate-
rial as described by Elwahy and coworkers.23 During the S-alkyl-
ation, which gave 18–20% yields of the target bis-triazoles, we
observed (TLC monitoring) the formation of oxadiazoles as second-
ary products. This may be attributed to reaction of the hydroxyl
group with the aminotriazoles giving the oxadiazole compounds
Crown ethers were discovered by Pederson at DuPont.9 Since
then, various structural changes have been made to the basic
crown ether structures in an attempt to enhance the selectivity
of these ligands and the stability of the complexes formed with
both metal and organic cations. These changes involve substitution
of the polyether ligand-containing oxygen donor atoms by sulfur
and/or nitrogen atoms.10 The incorporation of oxygen, nitrogen,
and sulfur donor atoms in the macrocycles will also markedly
affect their complexing properties because of the hard (O, N) and
soft (S) character of the donor atoms and the exodentate tendency
of the sulfide linkages.11 Other changes involve the insertion of
aromatic and/or heterocyclic ring systems into the macrocycles;12
heterocyclic groups provide rigidity, and in some cases are able to
form complexes through their soft donor atoms.13 The wide inter-
est in the construction of synthetic macrocyclic compounds con-
taining five- and six-membered heterocyclic rings as subunits
has led to the preparation of a range of such compounds which
have been shown to possess very interesting properties in a variety
* Corresponding author. Tel.: +98 918 1613794; fax: +98 861 4173406.
E-mail address: N_Foroughifar@yahoo.com (N. Foroughifar).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.12.014

N. Foroughifar et al. / Tetrahedron Letters 50 (2009) 836–839
837
N
N
N
N
N
N
Ar
SH
O
HS
O
Ar
N
N
N
N
Ar
2a-b
SH
CHO
CHO
N
O
O
NH2
X
X
1a X = (CH2)2
1b X = (CH2)3
3a-d
KOH/ EtOH
N
N
N
N
N
N
N
N
Y
Ar
S-K+ +K-S
Ar
N
N
N
N
Ar
S
S
Ar
N
N
N
N
Br
Br
Y
O
O
O
O
X
X
5a-f
4a-d
Ar= 4-pyridyl, 3-pyridyl
X= (CH2)2, (CH2)3
Y= (CH2)2, (CH2)3
Scheme 1.
Table 1
Schiff base compounds 3a–d
N
N
N
N
N
N
HS
SH
O
CHO
CHO
S
S
H2N
SH
Product
Ar
X
Yield (%)
S
N
N
O
O
3a
3b
3c
3d
4-Pyridyl
3-Pyridyl
4-Pyridyl
3-Pyridyl
(CH2)2
(CH2)2
(CH2)3
(CH2)3
68
68
70
66
X
O
1a X = (CH2)2
X = (CH2)3
X = (CH2)4
X
1b
1c
6a-c
pounds 3a–d with hot ethanolic potassium hydroxide solution)
were reacted with the appropriate dibromoalkanes in DMF under
reflux to give the azathia macrocycles 5a–f in good yields as re-
ported in Table 2.
As an extension of this study, we reacted 2-amino-5-mercapto-
1,3,4-thiadiazole with bis-aldehydes 1a–c25 to give Schiff bases
6a–c. The potassium salts 7a–c, prepared as before, were reacted
with dibromoalkanes of general formula Br(CH2)nBr (n = 2–4) to
give the macrocycles 8a–d in reasonable yields as reported in
Table 3.
KOH/ EtOH
N
Y
N
N
N
N
N
N
S-K+
+K-S
S
N
N
S
Br
Br
S
S
Y
S
S
N
N
N
O
O
O
O
X
X
The IR spectra of the 4-amino-5-(aroyl)-4H-1,2,4-triazole-3-thi-
ols 2a–b showed absorption bands at 3230 and 3400 cmÀ1 due to
the NH2 group, which were absent in the IR spectra of the bis
[o-(N-methylidenamino-5-aryl-3-thiol-4H-1,2,4-triazole-4-yl)phen-
oxy]alkanes 3a–d. Similarly, the 1H NMR spectra of 2a–b showed a
7a-c
8a-d
X= (CH2)2, (CH2)3,(CH2)4
Y= (CH2)2, (CH2)4
Scheme 2.
Table 2
Azathia crown ethers 5a–f
(as by-products) as reported in the literature.24 We next applied
the second strategy as outlined in Scheme 1.
Product
Ar
X
Y
Yield (%)
Reaction of bis-aldehydes 1a–b25 with 4-amino-5-(aroyl)-4H-
1,2,4-triazole-3-thiols 2a–b26 in acetic acid under reflux for 3 h
afforded the corresponding 1,2/1,3-bis[o-(N-methylidenamino-5-
aryl-3-thiol-4H-1,2,4-triazole-4-yl) phenoxy]alkanes 3a–d as re-
ported in Table 1. The products were obtained in reasonable yields.
Next, potassium salts 4a-d (obtained upon treatment of com-
5a
5b
5c
5d
5e
5f
4-Pyridyl
3-Pyridyl
4-Pyridyl
3-Pyridyl
4-Pyridyl
3-Pyridyl
(CH2)2
(CH2)2
(CH2)3
(CH2)3
(CH2)3
(CH2)3
(CH2)2
(CH2)2
(CH2)3
(CH2)3
(CH2)2
(CH2)2
61
62
58
60
68
65

838
N. Foroughifar et al. / Tetrahedron Letters 50 (2009) 836–839
Table 3
moved by filtration, and the resulting solution was poured into
Schiff bases 6a–c and azathia crown ethers 8a–d
water and a precipitate formed. The precipitate was filtered and
recrystallized from an appropriate solvent to give the pure azathia
crown macrocycles 8a–d.
Product
X
Y
Yield (%)
6a
6b
6c
8a
8b
8c
8d
(CH2)2
(CH2)3
(CH2)4
(CH2)2
(CH2)2
(CH2)3
(CH2)4
—
—
—
(CH2)2
(CH2)4
(CH2)2
(CH2)2
70
80
74
56
58
62
55
References and notes
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10. (a) Bradshaw, J. S. In Comprehensive Supramolecular Chemistry; Gokel, G. W.,
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1983, 38.
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Weber, E.; Kohler, H. J.; Reuter, H. J. J. Org. Chem. 1991, 56, 1236–1242.
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broad signal at d = 5.90 ppm attributed to the NH2 group which
was not present in the spectra of compounds 3a–d. In addition,
the absence of the IR absorptions and 1H NMR signals due to the
SH groups of compounds 3a–d and 6a–c further confirmed the
formation of azathia crown macrocycles 5a–f and 8a–d.
In summary, we have reported a simple and efficient method
for the preparation of azathia crown macrocycles containing two
triazoles or thiadiazole subunits. This procedure offers several
advantages such as good yields of cyclization products without
the need for high dilution conditions, short reaction times, and
simple purification.
14. (a) Bradshaw, J. S.; Huzzthy, P.; McDaniel, C. W.; Zhu, C. Y.; Dalley, N. K.; Izatt,
R. M. J. Org. Chem. 1990, 55, 3129–3137; (b) Bradshaw, J. S.; Thompson, P. K.;
Izatt, R. M. J. Heterocycl. Chem. 1984, 21, 897–901.
2. General procedure for the synthesis of bis-Schiff bases 3a–d
15. (a) Collier, C. P.; Mattersteig, G.; Wong, E. W.; Luo, Y.; Beverly, K.; Sampaio, J.;
Raymo, F. M.; Stoddart, J. F.; Heath, J. R. Science 2000, 289, 1172–1175; (b)
Elizabeth, A. J.; Eric, E. S. A.; Osgood, A. M.; Lisa, M. R.; Lawrence, B. B. Bioorg.
Med. Chem. Lett. 2003, 13, 1635–1638; (c) Jian, L.; Tington, L.; Yongmei, W. Eur.
J. Med. Chem. 2008, 43, 19–24; (d) Huang, S. T.; Kuo, H. S.; Hsiao, C. L.; Lin, Y. L.
Bioorg. Med. Chem. 2002, 10, 1947–1952.
16. Abbas, A. A. Tetrahedron 2004, 60, 1541–1548.
17. (a) Pellisard, D.; Luis, R. Tetrahedron Lett. 1972, 4589–4592; (b) Overman, L.
E. J. Org. Chem. 1972, 37, 4214–4218.
A solution of bis-aldehydes 1a–b (5 mmol) and 4-amino-5-(ar-
oyl)-4H-1,2,4-triazole-3-thiols 2a–b (10 mmol) in glacial acetic
acid (20 ml) was heated under reflux for 3 h. After cooling, the mix-
ture was poured into ice-water (50 ml). The precipitate that
formed was filtered and recrystallized from an appropriate solvent
to give the desired compounds 3a–d.
18. Sharghi, H.; Eshghi, H. Tetrahedron 1995, 51, 913–922.
19. Morphy, R. J.; Parker, D.; Alexander, R.; Bains, A.; Came, A. F.; Eaton, M. A. W.;
Harrison, A.; Millican, A.; Philipps, A.; Rhind, S. K.; Tetmas, R.; Weatherby, D.
J. Chem. Soc., Chem. Commun. 1988, 156–158.
3. General procedure for the synthesis of azathia crown
macrocycles 5a–f
20. Jurczak, J.; Kasprzyh, S.; Satanski, P.; Stankiewicz, T.; Lipkowski, P. Tetrahedron
1993, 49, 1478–1488.
Compounds 3a–d (0.15 mmol) were dissolved in hot ethanolic
KOH [prepared by dissolving KOH (0.30 mmol) in 20 ml of absolute
ethanol], and the solvent was then removed under vacuum. The
residue was dissolved in DMF (7 ml) and the appropriate dibro-
moalkane (0.15 mmol) was added. The mixture was refluxed for
5 min, during which time KBr separated out. The KBr was removed
by filtration, and the resulting solution was poured into water and
a precipitate formed. The precipitate was filtered and recrystallized
from H2O/DMF (2:1) to give the pure azathia crown macrocycles
5a–f.
21. (a) Tabushi, I.; Taniguchi, Y.; Kado, H. Tetrahedron Lett. 1977, 18, 1049–1052;
(b) Tabushi, I.; Okino, H.; Kuroda, Y. Tetrahedron Lett. 1976, 17, 4339–4342.
22. Kumar, S.; Bhalla, V.; Singh, H. Tetrahedron 1998, 54, 5575–5586.
23. Ibrahim, Y. A.; Elwahy, A. H. M.; Elkareish, G. M. M. J. Chem. Res. (S) 1994, 11,
414–415.
24. Elwahy, A. H. M.; Abbas, A. A. Tetrahedron 2000, 56, 885–895.
25. Bijev, A. T.; Prodanova, P. Heterocycl. Chem. 2007, 43, 306–313.
26. Reid, R. J.; Heindel, D. N. J. Heterocycl. Chem. 1976, 13, 925–926.
1,2-Bis[o-(N-methylidenamino-5-(4-pyridyl)-3-thiol-4H-1,2,4-triazole-4-yl)phen-
oxy]ethane (Table 1, entry 3a): IR (KBr):
m
(cmÀ1): 3070 (aromatic CH stretch.),
2698 (SH stretch.) 1599 (C@N), 1530, 1427 (C@C ring stretch.); 1H NMR
(300 MHz, DMSO-d6) d (ppm): 14.28 (s, 2H, 2 SH), 10.03 (s, 2H, 2 CH@N), 8.68
(d, 4H, Harom., J = 5.0 Hz), 7.87 (d, 2H, Harom., J = 7.7 Hz), 7.79 (d, 4H, Harom.
,
J = 5.1 Hz), 7.57 (t, 2H, Harom., J = 7.7 Hz), 7.30 (d, 2H, Harom., J = 8.4 Hz), 7.04 (t,
2H, Harom., J = 7.5 Hz), 4.53 (s, 4H, 2 OCH2). 13C NMR (75 MHz, DMSO-d6) d
(ppm): 65.1, 113.7, 120.5, 121.6, 122.4, 126.9, 133.3, 135.1, 147.1, 150.7, 159.1,
161.6, 163.2. Anal. Calcd for C30H24N10O2S2: C, 58.05; H, 3.90; N, 22.57; S,
10.33. Found: C, 57.85; H, 3.89; N, 22.45; S, 10.26.
4. General procedure for the synthesis of bis-Schiff bases 6a–c
A solution of bis-aldehydes 1a–c (5 mmol) and 2-amino-5-mer-
capto-1,3,4-thiadiazole (10 mmol) in glacial acetic acid (15 ml)
was refluxed for 3 h. After cooling, the mixture was poured into
ice-water (50 ml). The precipitate that formed was filtered and
recrystallized from an appropriate solvent to give the desired com-
pounds 6a–c.
1,2-Bis[o-(N-methylidenamino-5-(3-pyridyl)-3-thiol-4H-1,2,4-triazole-4-yl)phen-
oxy]ethane (Table 1, entry 3b):
IR (KBr):
m
(cmÀ1): 3070 (aromatic CH stretch.), 2728 (SH stretch.) 1600 (C@N),
1530, 1427 (C@C ring stretch.); 1H NMR (300 MHz, DMSO-d6) d (ppm): 14.25 (s,
2H, 2 SH), 10.15 (s, 2H, 2 CH@N), 9.03 (s, 2H, Harom.), 8.70 (s, 2H, Harom.), 8.23 (d,
2H, Harom., J = 7.7 Hz), 7.86 (d, 2H, Harom., J = 7.5 Hz), 7.56–7.60 (m, 4H, Harom.),
7.22 (d, 2H, Harom., J = 7.9 Hz), 7.07 (t, 2H, Harom., J = 7.5 Hz), 4.52 (s, 4H, 2 OCH2),
13C NMR (75 MHz, DMSO-d6) d (ppm): 66.3, 113.7, 120.6, 121.6, 122.4, 127.1,
132.8, 133.2, 134.4 135.1, 148.8, 151.1, 159.3, 161.6, 163.2. Anal. Calcd for
C30H24N10O2S2: C, 58.05; H, 3.90; N, 22.57; S, 10.33. Found: C, 57.72; H, 3.78; N,
22.38; S, 10.16.
5. General procedure for the synthesis of azathia crown
macrocycles 8a–d
1,2-Bis[o-(N-methylidenamino-5-(4-pyridyl)-3-thiol-4H-1,2,4-triazole-4-yl)phen-
Compounds 6a–c (0.15 mmol) were dissolved in hot ethanolic
KOH [prepared by dissolving KOH (0.3 mmol) in 10 ml of absolute
ethanol] and the solvent was then removed under vacuum. The
residue was dissolved in DMF (15 ml), and the appropriate dibro-
moalkane (0.15 mmol) was added. The mixture was refluxed for
15 min, during which time KBr separated out. The KBr was re-
oxy]propane (Table 1, entry 3c): IR (KBr):
t
(cmÀ1): 3068 (aromatic CH stretch.),
2731 (SH stretch.) 1599 (C@N), 1530, 1430 (C@C ring stretch.); 1H NMR
(300 MHz, DMSO-d6) d (ppm): 14.40 (s, 2H, 2 SH), 10.19 (s, 2H, 2CH@N), 8.73
(d, 4H, Harom., J = 5.1 Hz), 7.92 (d, 2H, Harom., J = 7.8 Hz), 7.85 (d, 4H, Harom.
,
J = 5.1 Hz), 7.57 (t, 2H, Harom., J = 7.8 Hz), 7.23 (d, 2H, Harom., J = 8.4 Hz), 7.05 (t,
2H, Harom., J = 7.5 Hz), 4.38 (t, 4H, 2OCH2 J = 5.5 Hz), 2.24 (t, 2H, CH2 J = 5.5 Hz).
13C NMR (75 MHz, DMSO-d6) d (ppm): 28.9, 65.2, 113.7, 120.5, 121.6, 122.4,

N. Foroughifar et al. / Tetrahedron Letters 50 (2009) 836–839
839
126.9, 133.1, 135.3, 147.0, 150.8, 159.1, 161.5, 163.2. Anal. Calcd for
C31H26N10O2S2: C, 58.66; H, 4.13; N, 22.07; S, 10.10. Found: C, 58.41; H, 4.02;
N, 22.25; S, 9.92.
(t, 2H, Harom., J = 7.5 Hz), 4.54 (t, 4H, 2OCH2, J = 5.6 Hz), 3.85 (s, 4H, 2SCH2), 2.31
(t, 2H, CH2 J = 5.5 Hz). 13C NMR (75 MHz, DMSO-d6) d (ppm): 29.4, 36.3 66.1,
113.7, 120.4, 121.8, 122.5, 127.0, 132.9, 133.2, 134.4 135.2, 148.8, 151.1, 159.3,
161.6, 163.2. MS (EI): m/z = 660 (M+), 630, 592, 578, 382, 278, 146 (base peak),
119, 105. Anal. Calcd for C33H28N10O2S2: C, 59.98; H, 4.27; N, 21.20; S, 9.71.
Found: C, 59.73; H, 4.22; N, 21.10; S, 9.56.
1,2-Bis[o-(N-methylidenamino-5-(3-pyridyl)-3-thiol-4H-1,2,4-triazole-4-yl)phen-
oxy]propane (Table 1, entry 3d): IR (KBr): m
(cmÀ1): 3075 (aromatic CH stretch.),
2705 (SH stretch.) 1605 (C@N), 1547, 1427 (C@C ring stretch.); 1H NMR
(300 MHz, DMSO-d6) d (ppm): 14.45 (s, 2H, 2 SH), 10.19 (s, 2H, 2 CH@N), 9.02
(s, 2H, Harom.) 8.70 (s, 2H, Harom.), 8.22 (d, 2H, Harom., J = 7.8 Hz), 7.81 (d, 2H,
Harom., J = 7.4 Hz), 7.55–7.59 (m, 4H, Harom.), 7.21 (d, 2H, Harom., J = 8.0 Hz), 7.08
(t, 2H, Harom., J = 7.4 Hz), 4.38 (t, 4H, 2 OCH2, J = 5.6 Hz), 2.25 (t, 2H, CH2
J = 5.7 Hz). 13C NMR (75 MHz, DMSO-d6) d (ppm): 29.0, 65.1, 113.7, 120.5,
121.6, 122.5, 127.0, 132.9, 133.2, 134.6 135.2, 147.1, 150.7, 159.1, 161.6, 163.2.
Anal. Calcd for C31H26N10O2S2: C, 58.66; H, 4.13; N, 22.07; S, 10.10. Found: C,
58.39; H, 4.08; N, 21.91; S, 9.96.
1,2-Bis[o-(N-methylidenamino-2-thiol-1,3,4-thiadiazole-5-yl)phenoxy]ethane
(Table 3, entry 6a): IR (KBr):
m
(cmÀ1): 3075 (aromatic CH stretch.), 2728
(SH stretch.) 1605 (C@N), 1532, 1428 (C@C ring stretch); 1H NMR (300 MHz,
DMSO-d6) d (ppm): 14.30 (s, 2H, 2SH), 10.21 (s, 2H, 2CH@N), 7.65 (d, 2H,
Harom., J = 5.0 Hz), 7.36 (t, 2H, Harom., J = 7.1 Hz), 7.19 (d, 2H, Harom.,
J = 8.0 Hz), 7.12 (t, 2H, Harom., J = 7.0 Hz), 4.59 (s, 4H, 2OCH2). 13C NMR
(75 MHz, DMSO-d6 75 MHz) d (ppm): 64.8, 113.4, 121.5, 123.0, 128.1, 136.4,
159.6, 163.2, 163.3, 174.0. Anal. Calcd for C20H16N6O2S4: C, 47.98; H, 3.22;
N, 16.79; S, 25.62. Found: C, 47.71; H, 3.17; N, 16.56; S, 25.35.
2,3:16,17-Dibenzo-6,7:12,13-bis[5-(4-pyridyl)]-1,2,4-triazolo-[1,18,8,11,5,6,13,14]
dioxa dithia tetraaza cycloicosa-4,14-diene (Table 2, entry 5a): IR (KBr):
m
1,2-Bis[o-(N-methylidenamino-2-thiol-1,3,4-thiadiazole-5-yl)phenoxy]propane
(cmÀ1): 3070 (aromatic CH stretch.), 1599 (C@N), 1525, 1437 (C@C ring
stretch.); 1H NMR (300 MHz, DMSO-d6) d (ppm): 9.18 (s, 2H, 2CH@N), 8.70 (d,
4H, Harom., J = 4.8 Hz), 7.92 (d, 2H, J = 7.6 Hz), 7.80 (d, 4H, Harom., J = 4.8 Hz), 7.60
(Table 3, entry 6b): IR (KBr): m
(cmÀ1): 3075 (aromatic CH stretch.), 2725 (SH
stretch.) 1605 (C@N), 1530, 1432 (C@C ring stretch.); 1H NMR (300 MHz,
DMSO-d6) d (ppm): 14.21 (s, 2H, 2SH), 10.19 (s, 2H, 2CH@N), 7.61–7.70 (m, 4H,
Harom.), 7.24 (d, 2H, Harom. J = 8.0 Hz), 7.07 (t, 2H, Harom., J = 6.9 Hz), 4.40 (t, 4H,
2OCH2, J = 5.4 Hz), 2.26 (t, 2H, CH2, J = 5.4 Hz). 13C NMR (75 MHz, DMSO-d6) d
(ppm): 29.1, 65.1, 113.6, 121.8, 122.9, 128.3, 136.3, 159.6, 163.1, 163.3, 174.9.
Anal. Calcd for C21H18N6O2S4: C, 49.01; H, 3.53; N, 16.33; S, 24.92. Found: C,
48.88; H, 3.66; N, 16.51; S, 24.72.
(t, 2H, Harom., J = 8.0 Hz), 7.26 (d, 2H, Harom., J = 8.5 Hz), 7.05 (t, 2H, Harom.
,
J = 7.5 Hz), 4.54 (s, 4H, 2OCH2), 3.71 (s, 4H, 2SCH2). 13C NMR (75 MHz, DMSO-
d6) d (ppm): 36.1, 67.8, 114.2, 120.0, 121.7, 122.5, 127.5, 134.0, 136.0, 147.1,
150.7, 159.2, 162.8, 164.7. MS (EI): m/z = 646 (M+), 620, 618, 589, 578, 382,
264, 178, 146 (base peak), 119, 105. Anal. Calcd for C32H26N10O2S2: C, 59.43; H,
4.05; N, 21.66; S, 9.92. Found: C, 59.15; H, 3.96; N, 21.50; S, 9.85.
1,2-Bis[o-(N-methylidenamino-2-thiol-1,3,4-thiadiazole-5-yl)phenoxy]butane
2,3:16,17-Dibenzo-6,7:12,13-bis[5-(3-pyridyl)]-1,2,4-triazolo-[1,18,8,11,5,6,13,14]-
(Table 3, entry 6c): IR (KBr): m
(cmÀ1): 3070 (aromatic CH stretch.), 2731 (SH
dioxa dithia tetraaza cycloicosa-4,14-diene (Table 2, entry 5b): IR (KBr):
m
(cmÀ1):
stretch.) 1600 (C@N), 1530, 1427 (C@C ring stretch.); 1H NMR (300 MHz,
DMSO-d6) d (ppm): 14.25 (s, 2H, 2 SH), 10.38 (s, 2H, 2 CH@N), 7.60–7.70 (m,
4H, Harom.), 7.24 (d, 2H, Harom. J = 8.0), 7.06 (t, 2H, Harom., J = 7.0), 4.23 (br s, 4H,
2OCH2), 2.00 (br s, 4H, 2CH2). 13C NMR (75 MHz, DMSO-d6) d (ppm): 27.6, 64.9,
113.6, 121.3, 122.5, 128.1, 136.1, 159.8, 163.2, 163.4, 175.0. Anal. Calcd for
C22H20N6O2S4: C, 49.98; H, 3.81; N, 15.90; S, 24.26. Found: C, 49.74; H, 3.75; N,
15.72; S, 24.01.
3065 (aromatic CH stretch.), 1609 (C@N), 1530, 1445 (C@C ring stretch.); 1H NMR
(300 MHz, DMSO-d6) d (ppm): 9.24 (s, 2H, CH@N), 9.03 (s, 2H, Harom.) 8.71 (s, 2H,
Harom.), 8.20 (d, 2H, Harom., J = 7.7 Hz), 7.85 (d, 2H, Harom., J = 7.0 Hz), 7.55-7.59 (m,
4H, Harom.), 7.23 (d, 2H, Harom., J = 8.1 Hz), 7.08 (t, 2H, Harom., J = 7.3 Hz), 4.53 (s, 4H,
2OCH2), 3.72 (s, 4H, 2SCH2). 13C NMR (75 MHz, DMSO-d6) d (ppm): 34.0 67.1,
113.7, 120.5, 121.5, 122.3, 127.1, 132.8, 133.2, 134.1 134.9, 148.9, 151.0, 159.5,
162.3, 163.9. MS (EI): m/z = 646 (M+), 620, 618, 589, 578, 564, 264, 146 (base
peak), 119, 105, 91. Anal. Calcd for C32H26N10O2S2: C, 59.43; H, 4.05; N, 21.66; S,
9.92. Found: C, 59.61; H, 4.34; N, 21.95; S, 9.67.
2,3:18,19-Dibenzo-6,8:13,15 bis-1,3,4-thiadiazolo-[1,20,7,9,12,14,5,16] dioxa
tetrathia diaza cyclodocosa-4,16-diene (Table 3, entry 8a): IR (KBr):
m
(cmÀ1):
3070 (aromatic CH stretch.), 1600 (C@N), 1540, 1440 (C@C ring stretch.); 1H
NMR (300 MHz, DMSO-d6) d (ppm): 9.47 (s, 2H, 2CH@N), 7.57–7.62 (m, 4H,
Harom.), 7.29 (d, 2H, Harom, J = 8.1 Hz), 7.09 (t, 2H, Harom, J = 7.4 Hz), 4.77 (s, 4H,
2OCH2), 3.75 (s, 4H, 2SCH2). 13C NMR (75 MHz, DMSO-d6) d (ppm): 34.0, 66.6,
113.6, 121.8, 122.9, 128.4, 136.6, 159.5, 163.2, 163.4, 174.9. MS (EI): m/z = 526
(M+), 495, 467, 439, 411, 324, 271, 133, 121, 83 (base peak). Anal. Calcd for
C22H18N6O2S4: C, 50.17; H, 3.44; N, 15.96; S, 24.35. Found: C, 49.89; H, 3.39; N,
15.73; S, 24.12.
2,3:17,18-Dibenzo-6,7:13,14-bis[5-(4-pyridyl)]-1,2,4-triazolo-[1,19,8,12,5,6,14,15]-
dioxa dithia tetraaza cyclodocosa-4,15-diene (Table 2, entry 5c): IR (KBr):
m
(cmÀ1):
3075 (aromatic CH stretch.), 1599 (C@N), 1530, 1445 (C@C ring stretch.); 1H NMR
(300 MHz, DMSO-d6) d (ppm): 9.29 (s, 2H, 2CH@N), 8.76 (d, 4H, Harom., J = 5.0 Hz),
7.77–7.98 (m, 6H, Harom.), 7.64 (t, 2H, Harom., J = 7.8 Hz), 7.26 (d, 2H, Harom.
,
J = 8.3 Hz), 7.13 (t, 2H, Harom., J = 7.5 Hz), 4.38 (t, 4H, 2 OCH2 J = 5.6 Hz), 3.38 (t, 4H,
2SCH2 J = 5.5 Hz), 2.29-2.35 (m, 4H, 2CH2). 13C NMR (75 MHz, DMSO-d6) d (ppm):
28.2, 29.0, 33.8, 66.0, 113.7, 120.6, 121.6, 122.4, 127.0, 133.4, 135.0, 147.1, 151.0,
159.0, 161.5, 163.2. MS (EI): m/z = 674 (M+), 646, 634, 618, 604, 578, 396, 278, 146
(base peak), 119, 105, 91. Anal. Calcd for C34H30N10O2S2: C, 60.52; H, 4.48; N,
20.76; S, 9.50. Found: C, 60.22; H, 4.33; N, 20.51; S, 9.41.
2,3:19,20-Dibenzo-6,8:14,16 bis-1,3,4-thiadiazolo-[1,21,7,9, 13,15,5,17]dioxa
tetrathia diaza cyclotetracosa-4,17-diene (Table 3, entry 8b): IR (KBr):
m
(cmÀ1): 3075 (aromatic CH stretch.), 1610 (C@N), 1547, 1438 (C@C ring
stretch.); 1H NMR (300 MHz, CD3COCD3) d (ppm): 9.49 (s, 2H, 2CH@N), 8.23 (d,
2,3:17,18-Dibenzo-6,7:13,14-bis[5-(3-pyridyl)]-1,2,4-triazolo-[1,19,8,12,5,6,14,15]-
2H, Harom., J = 7.5 Hz), 7.61 (t, 2H, Harom, J = 8.0 Hz), 7.32 (d, 2H, Harom,
dioxa dithia tetraaza cyclodocosa-4,15-diene: (Table 2, entry 5d): IR (KBr):
m
J = 8.1 Hz), 7.11 (t, 2H, Harom, J = 7.4 Hz), 4.41 (br s, 4H, 2OCH2), 3.76 (br s,
4H, 2SCH2), 2.27–2.34 (m, 4H, 2CH2). 13C NMR (75 MHz, CD3COCD3) d (ppm):
28.0, 29.1, 34.0, 66.2, 113.7, 121.6, 122.7, 128.4, 136.0, 159.5, 163.1, 163.3,
175.0. MS (EI): m/z = 554 (M+), 523, 495, 467, 425, 285, 133, 83 (base peak).
Anal. Calcd for C24H22N6O2S4: C, 51.96; H, 4.00; N, 15.15; S, 23.12. Found:
52.18; H, 4.12; N, 15.32; S, 23.37.
(cmÀ1): 3068 (aromatic CH stretch.), 1610 (C@N), 1527, 1440 (C@C ring stretch.);
1H NMR (300 MHz, DMSO-d6) d (ppm): 9.23 (s, 2H, CH@N), 9.02 (s, 2H, Harom.),
8.70 (s, 2H, Harom.), 8.24 (d, 2H, H arom., J = 7.8 Hz), 7.85 (d, 2H, Harom., J = 7.2 Hz),
7.55–7.59 (m, 4H, Harom.), 7.21 (d, 2H, Harom., J = 8.1 Hz), 7.07 (t, 2H, Harom.
,
J = 7.5 Hz), 4.38 (t, 4H, 2OCH2, J = 5.6 Hz), 3.85 (d, 4H, 2SCH2 J = 5.6 Hz), 2.28–2.34
(m, 4H, 2CH2). 13C NMR (75 MHz, DMSO-d6) d (ppm): 28.2, 29.1, 34.0 66.2, 113.7,
120.3, 121.6, 122.5, 127.1, 132.8, 133.2, 134.4 135.0, 149.0, 151.1, 159.3, 161.4,
163.1. MS (EI): m/z = 674 (M+), 646, 634, 604, 618, 578, 396, 278, 146 (base peak),
119, 105, 91. Anal. Calcd for C34H30N10O2S2: C, 60.52; H, 4.48; N, 20.76; S, 9.50.
Found: C, 60.28; H, 4.24; N, 20.41; S, 9.37.
2,3:18,19-Dibenzo-6,8:13,15 bis-1,3,4-thiadiazolo-[1,20,7,9, 12,14,5,16]dioxa
tetrathia diaza cyclotricosa-4,16-diene (Table 3, entry 8c): IR (KBr):
m
(cmÀ1): 3070 (aromatic CH stretch.), 1600 (C@N), 1535, 1436 (C@C ring
stretch.); 1H NMR (300 MHz, CD3COCD3) d (ppm): 9.48 (s, 2H, 2CH@N), 8.21
(d, 2H, Harom., J = 7.3 Hz), 7.63 (t, 2H, Harom., J = 7.9 Hz), 7.33 (d, 2H, Harom.
,
2,3:16,17-Dibenzo-6,7:12,13-bis[5-(4-pyridyl)]-1,2,4-triazolo-[1,18,8,11,5,6,13,14]-
J = 8.3 Hz), 7.13 (t, 2H, Harom., J = 7.5 Hz), 4.40 (br s, 4H, 2OCH2), 3.78 (s, 4H,
2SCH2), 2.26 (br s, 2H, CH2). 13C NMR (75 MHz, CD3COCD3) d (ppm): 29.1,
34.1, 66.5, 113.6, 121.8, 122.9, 128.5, 136.1, 159.5, 163.2, 163.3, and 175.0.
MS (EI): m/z = 540 (M+), 509, 481, 453, 285, 133, 83 (base peak). Anal. Calcd
for C23H20N6O2S4: C, 51.09; H, 3.73; N, 15.54; S, 23.72. Found: C, 50.87; H,
3.69; N, 15.63; S, 23.81.
dioxa dithia tetraaza cyclohenicosa-4,14-diene (Table 2, entry 5e): IR (KBr):
(cmÀ1): 3075 (aromatic CH stretch.), 1599 (C@N), 1530, 1438 (C@C ring stretch.);
1H NMR (300 MHz, DMSO-d6) d (ppm): 9.21 (s, 2H, 2CH@N), 8.80 (d, 4H, Harom.
m
,
J = 5.1 Hz), 7.92–8.07 (m, 6H, Harom.), 7.61 (t, 2H, Harom., J = 7.6 Hz), 7.25 (d, 2H,
Harom., J = 8.2 Hz), 7.08 (t, 2H, Harom., J = 7.3 Hz), 4.38 (t, 4H, 2 OCH2 J = 5.6 Hz), 3.38
(s, 4H, 2SCH2), 2.32 (d, 2H, CH2 J = 5.6 Hz). 13C NMR (75 MHz, DMSO-d6) d (ppm):
29.1, 34.0, 66.1, 113.9, 120.5, 121.5, 122.4, 127.1, 133.4, 134.9, 147.1, 150.6, 159.1,
161.6, 163.2. MS (EI): m/z = 660 (M+), 635, 632, 630, 592, 578, 382, 278, 146 (base
peak), 119, 105. Anal. Calcd for C33H28N10O2S2: C, 59.98; H, 4.27; N, 21.20; S, 9.71.
Found: C, 59.74; H, 4.19; N, 21.04; S, 9.59.
2,3:18,19-Dibenzo-6,8:13,15 bis-1,3,4-thiadiazolo-[1,20,7,9, 12,14,5,16]dioxa
tetrathia diaza cyclotetracosa-4,16-diene (Table 3, entry 8d): IR (KBr):
m
(cmÀ1): 3074 (aromatic CH stretch.), 1606 (C@N), 1540, 1435 (C@C ring
stretch.); 1H NMR (300 MHz, CD3COCD3) d (ppm): 9.47 (s, 2H, 2CH@N), 8.21
(d, 2H, Harom., J = 7.5 Hz), 7.60 (t, 2H, Harom., J = 8.1 Hz), 7.30 (d, 2H, Harom.
,
2,3:16,17-Dibenzo-6,7:12,13-bis[5-(3-pyridyl)]-1,2,4-triazolo-[1,18,8,11,5,6,13,14]
J = 8.5 Hz), 7.11 (t, 2H, Harom., J = 7.4 Hz), 4.21 (br s, 4H, 2OCH2), 3.76 (s, 4H,
2SCH2), 1.99 (br s, 4H, 2CH2). 13C NMR (75 MHz, CD3COCD3) d (ppm): 27.6,
34.2, 64.8, 113.7, 121.5, 122.7, 128.4, 136.1, 159.8, 163.1, 163.3, and 175.0.
MS (EI): m/z = 554 (M+), 495, 467, 439, 352, 299, 133, 121, 83, 57 (base
peak). Anal. Calcd for C24H22N6O2S4: C, 51.96; H, 4.00; N, 15.15; S, 23.12.
Found: 51.75; H, 3.88; N, 14.87; S, 22.97.
dioxa dithia tetraaza cyclohenicosa-4,14-diene (Table 2, entry 5f): IR (KBr):
m
(cmÀ1): 3075 (aromatic CH stretch.), 1599 (C@N), 1530, 1445 (C@C ring
stretch.); 1H NMR (300 MHz, DMSO-d6) d (ppm): 9.25 (s, 2H, CH@N), 9.04
(s, 2H, Harom.) 8.69 (s, 2H, Harom.), 8.25 (d, 2H, Harom., J = 7.9 Hz), 7.86 (d, 2H,
Harom., J = 7.1 Hz), 7.57–7.60 (m, 4H, Harom.), 7.27 (d, 2H, Harom., J = 8.3 Hz), 7.07