Synthesis and antimicrobial studies of new N,N'-[5,5'-{2,2'-(bis-alkoxy) bis(2,1-phenylene)]bis(4-acetyl-4,5-dihydro-1,3,4-thiadiazole-5, 2-diyl)]diacetamide

Article abstract of DOI:10.1007/s12039-012-0247-z

The bisthiadiazolines 4a(a'-f ') and 4b(a'-f ') built around the various rigid chains have been synthesized in good yields by refluxing bisthiosemicarbazones 3a(a'-f ') and 3b(a'-f ') in acetic anhydride medium. The reaction of bisaldehydes 2a(a'-f ') and

Full text of DOI:10.1007/s12039-012-0247-z

c
J. Chem. Sci. Vol. 124, No. 3, May 2012, pp. 703–715. ꢀ Indian Academy of Sciences.
Synthesis and antimicrobial studies of new N,Nꢁ-[5,5ꢁ-{2,2ꢁ-(bis-alkoxy)
bis(2,1-phenylene)]bis(4-acetyl-4,5-dihydro-1,3,4-thiadiazole-5,
2-diyl)]diacetamide
MOHAMAD YUSUF∗, INDU SOLANKI and PAYAL JAIN
Department of Chemistry, Punjabi University, Patiala 147 002, India
e-mail: yusuf_sah04@yahoo.co.in
MS received 23 September 2011; revised 25 November 2011; accepted 14 December 2011
Abstract. The bisthiadiazolines 4a(aꢁ-fꢁ) and 4b(aꢁ-fꢁ) built around the various rigid chains have been syn-
thesized in good yields by refluxing bisthiosemicarbazones 3a(aꢁ-fꢁ) and 3b(aꢁ-fꢁ) in acetic anhydride medium.
The reaction of bisaldehydes 2a(aꢁ-fꢁ) and 2b(aꢁ-fꢁ) with thiosemicarbazide under alcoholic medium yielded
3a(aꢁ-fꢁ) and 3b(aꢁ-fꢁ) and the former were obtained from the reaction of 2/4-hydroxybenzaldehyde with suit-
able alkylating agent in the presence of anhydrous K2CO3/dry acetone and Bu4N+I− (PTC). The intermedi-
ates and final compounds have been characterized from the rigorous analysis of their IR, 1H-NMR, 13C-NMR,
ESI-Mass and elemental analysis. The antibacterial and antifungal activities of the prepared compounds were
also evaluated against the Klubsellia pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus
aureus, Bacillius subtilis and Aspergillius janus and Pencillium glabrum strains, respectively. The formation
and antimicrobial behaviour of the bisthiadiazolines 4a(aꢁ-fꢁ) and 4b(aꢁ-fꢁ) are found to be independent of
nature of the internal spacer unit.
Keywords. Cyclization; bisaldehydes; bisthiosemicarbazones; bisthiadiazolines and antimicrobial activity.
1. Introduction
bisthiadiazolines built around the intermediate chains
of rigid geometry. The major interest behind this study
was to investigate the effect of the internal unit (olefinic/
alkynic/aromatic) upon the formation and the antimicro-
bial behaviour of the final bisheterocyclic compounds.
The heterocyclic compounds bearing nitrogen and sul-
phur atoms constitute the core structure of a number of
biologically significant derivatives. 1,3,4-Thiadiazolines
are the heterocyclic substrates containing three hetero-
atoms (N, N and S) in a five-membered ring and these
compounds have been the subject of major attraction in
the past due to their significant biological activities.1,2
These substrates have also been used in dyes, optically
active liquid crystals and photographic materials and
many of their derivatives have also been reported as her-
bicides, insecticides, fungicides, bactericides and anthel-
mintics.3,4 These heterocycles are also found to possess
antihypertensive,5 anticonvulsive6 and many related
activities.7 Thiadiazolines are usually synthesized from
the cyclization reaction of thiosemicarbazones and the
later derivatives are also associated with variety of
biological and industrial applications.8–20 By keeping
this aspect in view and in continuation of our researches
on the synthesis of heterocyclic compounds, present
investigations have been focused on the synthesis of
2. Experimental
Melting points reported are uncorrected. IR spec-
tra were scanned in KBr pellets on a Perkin Elmer
1
RXIFT Infrared spectrophotometer. H-NMR spectra
were recorded on a 400 MHz Bruker spectrometer using
TMS as the internal standard. The mass spectra have
been scanned on the Waters Micromass Q-T of Micro
(ESI) spectrometer. TLC plates were coated with sili-
ca gel suspended in MeOH-CHCl3 and iodine vapours
were used as visualizing agent.
2.1 Synthesis of 2,2ꢁ-[but-2-ene-1,4-diylbis(oxy)]
benzaldehyde 2aaꢁ
A suspension of 2-hydroxybenzaldehyde (1.22 g,
0.01 mol),
trans-1,4-dibromo-2-butene
(1.06 g,
∗For correspondence
0.005 mol) and tetrabutylammonium iodide (1.0 g) in
703

704
Mohamad Yusuf et al.
dry acetone (25 ml) was refluxed for 6 h with continu- 2acꢁ: Cream solid, Yield 69%; m.p.: 98–100◦C. IR
ous stirring. The progress of reaction was monitored by (KBr) cm−1 3070 (aromatic C-H), 2934 (methylene
1
TLC. After the completion of reaction, the reaction mix- C-H), 2849, 2761 (aldehydic C-H), 1684 (C=O); H-
ture turned to a colourless mass which was poured into NMR (CDCl3): δ 10.43 (2H, s, 1, 1ꢁ-CHO), 7.79 (2H,
iced-HCl to obtain a crude product that was crystallized d, Jo = 7.6 Hz, H-6, 6ꢁ), 7.51 (4H, m, H-4, 4ꢁ, 5, 5ꢁ),
with MeOH to yield a pure bisaldehyde 2aaꢁ.
7.32 (2H, m, H-4ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ), 7.02 (4H, m, H-3, 3ꢁ, 3ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ),
5.28 (4H, s, OCH2); 13C-NMR (CDCl3): δ 189.36 (1, 1ꢁ-
CHO), 160.67 (C-2, 2ꢁ), 136.04 (C-5, 5ꢁ), 134.26 (C-1ꢁꢁꢁꢁ,
2ꢁꢁꢁꢁ), 129.27 (C-3ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 129.00 (C-4ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ), 128.96
(C-1, 1ꢁ), 125.10 (C-6, 6ꢁ), 121.30 (C-4, 4ꢁ), 112.79 (C-
3, 3ꢁ), 68.62 (OCH2); MS(ESI): (M+1)+ = 347; Anal.
Calc. for C22H18O4: Calc. C, 76.30%; H, 5.20%; Found
C, 76.24%; H, 5.15%.
2aaꢁ: Brown solid, Yield 81%; m.p.: 228–230◦C. IR
(KBr) cm−1 3091 (aromatic C-H), 2921 (methylene
1
C-H), 2868, 2741 (aldehydic C-H), 1675 (C=O); H-
NMR (CDCl3): δ 10.48 (2H, s, 1, 1ꢁ-CHO), 7.75 (2H,
d, Jo = 7.6 Hz, H-6, 6ꢁ), 7.57 (2H, t, J = 7.3 Hz, H-
4, 4ꢁ), 7.08 (2H, d, Jo = 8.9 Hz, H-5, 5ꢁ), 7.04 (2H,
d, Jo = 7.4 Hz, H-3, 3ꢁ), 6.20 (2H, brs, OCH2CH=),
4.77 OCH2CH=); 13C-NMR (CDCl3): δ 189.00 (1, 1ꢁ-
CHO), 160.67 (C-2, 1ꢁ-CHO), 160.67 (C-2, 2ꢁ), 135.90
(C-5, 5ꢁ), 128.72 (C-1, 1ꢁ), 127.87 (OCH2CH=), 125.12
(C-6, 6ꢁ), 121.11 (C-4, 4ꢁ), 112.77 (C-3, 3ꢁ), 68.62
(OCH2CH=), MS(ESI): m/z (M+Na)+ = 319; Anal.
Calc. for C18H16O4: Calc. C, 72.97%; H, 5.40%; Found
C, 72.90%; H, 5.47%.
2.4 Synthesis of 2,2ꢁ-[1,4-phenylenebis(methylene)]
bis(oxy)dibenzaldehyde 2adꢁ
The bisaldehyde 2adꢁ was prepared from the reac-
tion of 2-hydroxybenzaldehyde (1.22 g, 0.01 mol) with
α,αꢁ-dibromo-p-xylene (1.32 g, 0.005 mol) under the
similar conditions as described above for 2aaꢁ.
2.2 Synthesis of 2,2ꢁ-[but-2-yne-1,4-diylbis(oxy)]
benzaldehyde 2abꢁ
2adꢁ: Off white solid, Yield 75%; m.p.: 178–180◦C.
IR (KBr) cm−1 3070 (aromatic C-H str), 2934 (methy-
lene C-H), 2849, 2761 (aldehydic C-H), 1680 (C=O);
1H-NMR (CDCl3): δ 10.52 (2H, s, 1, 1ꢁ-CHO), 7.80
(2H, d, Jo = 7.4 Hz, H-6, 6ꢁ), 7.57 (2H, t, J =
7.3 Hz, H-4, 4ꢁ), 7.52 (4H, s, H-2ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ),
7.13 (2H, d, 7.13 (2H, d, J = 8.3 Hz, H-5, 5ꢁ), 7.06
(2H, t, Jo = 7.3 Hz, H-3, 3ꢁ), 5.25 (4H, s, OCH2);
13C-NMR (CDCl3): δ 189.36 (1, 1ꢁ-CHO), 160.67 (C-
2, 2ꢁ), 136.04 2ꢁ), 136.04 (C-5, 5ꢁ), 134.78 (C-1ꢁꢁꢁꢁ,
4ꢁꢁꢁꢁ),129.27 (C-2ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 128.96 (C-1, 1ꢁ),
125.10 (C-6, 6ꢁ), 121.30 (C-4, 4ꢁ), 112.79 (C-3, 3ꢁ),
68.62 (OCH2); MS(ESI): m/z (M+Na)+ = 369; Anal.
Calc. for C22H18O4: Calc. C, 76.30%; H, 5.20%; Found
C, 76.34%; H, 5.26%.
The bisaldehyde 2abꢁ was obtained from the reaction
of 2-hydroxybenzaldehyde (1.22 g, 0.01 mol) with 1,4-
dichloro-2-butyne (0.64 g, 0.005 mol) under the similar
conditions as described above for 2aaꢁ.
2abꢁ: Black solid, Yield 61%; m.p.: 238–240◦C. IR
(KBr) cm−1 3065 (aromatic C-H), 2940 (methylene
1
C-H), 2860, 2740 (aldehydic C-H), 1670 (C=O); H-
NMR (DMSO-d6): δ 10.48 (2H, s, 1, 1ꢁ-CHO), 7.75
(2H, d, Jo = 7.6 Hz, H-6, 6ꢁ), 7.55 (2H, t, J = 7.3 Hz,
H-4, 4ꢁ), 7.07 (2H, d, Jo = 8.4 Hz, H-5, 5ꢁ), 7.04 (2H,
d, Jo = 7.4 Hz, H-3, 3ꢁ), 5.12 (4H, brs, OCH2CH=);
13C-NMR (DMSO-d6): δ 190.01 (1, 1ꢁ-CHO), 160.65
(C-2, 2ꢁ), 135.28 (C-5, 5ꢁ), 128.24 (C-1, 1ꢁ), 125.01 (C-
6, 6ꢁ), 121.11 (C-4, 4ꢁ), 113.12 (C-3, 3ꢁ), 82.05 (C-1ꢁꢁꢁꢁ,
2ꢁꢁꢁꢁ), 55.04 (OCH2), 82.05 (C-1ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁ); MS(ESI): m/z
(M+Na)+ = 317; Anal. Calc. for C18H14O4: Calc. C,
73.47%; H, 4.76%; Found C, 73.43%; H, 4.72%.
2.5 Synthesis of 2,2ꢁ-[biphenyl-4,4ꢁ-diylbis(methylene)]
bis(oxy)benzaldehyde 2aeꢁ
The bisaldehyde 2aeꢁ was synthesized from the reaction
of 2-hydroxybenzaldehyde (1.22 g, 0.01 mol) with 4,4ꢁ-
bischloromethyl-di-phenyl (1.25 g, 0.005 mol) under
the similar conditions as described above for 2aaꢁ.
2.3 Synthesis of 2,2ꢁ-[1,2-phenylenebis(methylene)]
bis(oxy)dibenzaldehyde 2acꢁ
2aeꢁ: Cream solid, Yield 65%; m.p.: 180–182◦C. IR
The bisaldehyde 2acꢁ was synthesized from the reaction
of 2-hydroxybenzaldehyde (1.22 g, 0.01 mol) with α,
αꢁ-dibromo-o-xylene (1.32 g, 0.005 mol) under the simi-
lar conditions as described above for 2aaꢁ.
(KBr) cm−1 3071 (aromatic C-H), 2940 (methylene
1
C-H), 2891, 2721 (aldehydic C-H), 1688 (C=O); H-
NMR (CDCl3): δ 10.61 (2H, s, 1, 1ꢁ-CHO), 7.90 (2H,

Synthesis of bisthiadiazolines
705
d, J = 6.9 Hz, H-6, 6ꢁ), 7.67 (4H, d, J = 8.1 Hz, (C-1, 1ꢁ), 128.46 (C-2, 2ꢁ, 6, 6ꢁ), 114.72 (C-3, 3ꢁ, 5,
H-3ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁꢁ), 7.58 (2H, td, J = 4.6, 6.7 Hz, 5ꢁ), 82.05 (C-1ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁ), 55.1 (OCH2); MS(ESI): m/z
H-4, 4ꢁ), 7.55 (4H, d, J = 5.2 Hz, H-2ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ, (M+Na)+ = 319; Anal. Calc. for C18H14O4: Calc. C,
6ꢁꢁꢁꢁꢁ), 7.10 (2H, dd, J = 3.6, 7.5 Hz, H-5, 5ꢁ), 7.08 73.47%; H, 4.76%; Found C, 73.42%; H, 4.70%.
(2H, d, Jo = 8.1 Hz, H-3, 3ꢁ), 5.27 (4H, s, OCH2);
13C-NMR (CDCl3): δ 188.70 (1, 1ꢁ-CHO), 160.49 (C-
2, 2ꢁ), 139.64 (C-4ꢁꢁꢁꢁ, 4ꢁꢁꢁꢁꢁ), 135.78 (C-1ꢁꢁꢁꢁ, 1ꢁꢁꢁꢁꢁ), 135.70
(C-5, 5ꢁ), 127.68 (C-3ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁꢁ), 127.73 (C-1,
1ꢁ), 124.48 (C-6, 6ꢁ), 120.58 (C-4, 4ꢁ), 113.22 (C-3, 3ꢁ),
69.59 (OCH2); MS(ESI): m/z (M+Na)+ = 445; Anal.
Calc. for C28H22O4: Calc. C, 79.62%; H, 5.21%; Found
C, 79.56%; H, 5.28%.
2.8 Synthesis of 4,4ꢁ-[1,2-phenylenebis(methylene)]
bis(oxy)dibenzaldehyde 2bcꢁ
The bisaldehyde 2bcꢁ was prepared from the reaction of
4-hydroxybenzaldehyde (1.22 g, 0.01 mol) with α, αꢁ-
dibromo-o-xylene (1.32 g, 0.005 mol) under the similar
conditions as described above for 2aaꢁ.
2.6 Synthesis of 4,4ꢁ-[but-2-ene-1,4-diylbis(oxy)]
benzaldehyde 2baꢁ
2bcꢁ: Off white solid, Yield 81%; m.p.: 146–148◦C.
IR (KBr) cm−1 3071 (aromatic C-H), 2940 (methylene
The bisaldehyde 2baꢁ was obtained from the reac-
tion of 4-hydroxybenzaldehyde (1.22 g, 0.01 mol) with
trans-1,4-dibromo-2-butene (1.06 g, 0.005 mol) under
the similar conditions as described above for 2aaꢁ.
1
C-H), 2891, 2721 (aldehydic C-H), 1688 (C=O); H-
NMR (CDCl3): δ 9.78 (2H, s, 1, 1ꢁ-CHO), 7.74 (4H, d,
Jo = 8.6 Hz, H-2, 2ꢁ, 6, 6ꢁ), 7.47 (2H, dd, J = 3.3,
5.2 Hz, H-4ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ), 7.33 (2H, dd, J = 3.6, 5.4 Hz, H-
3ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 7.02 (4H, d, Jo = 8.6 Hz, H-3, 3ꢁ, 5, 5ꢁ),
5.23 (4H, s, OC (4H, s, OCH2); 13C-NMR (CDCl3): δ
190.74 (1, 1ꢁ-CHO), 163.41 (C-4, 4ꢁ), 134.25 (C-1, 1ꢁ),
132.06 (C-1ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁ), 130.35 (C-2, 2ꢁ, 6, 6ꢁ), 129.37 (C-
3ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 129.02 (C-4ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ), 115.03 (C-3, 3ꢁ, 5, 5ꢁ),
68.34 (OCH2); MS(ESI): m/z (M+Na)+ = 369; Anal.
Calc. for C22H18O4: Calc. C, 76.30%; H, 5.20%; Found
C, 76.35%; H, 5.25%.
2baꢁ: Brown solid, Yield 79%; m.p.: 126–128◦C. IR
(KBr) cm−1 3071 (aromatic C-H), 2921 (methylene
1
C-H), 2863, 2745 (aldehydic C-H), 1681 (C=O); H-
NMR(CDCl3): δ 9.79 (2H, s, 1, 1ꢁ-CHO), 7.76 (4H,
dt, J = 2.6, 9.5 Hz, H-2, 2ꢁ, 6, 6ꢁ), 6.99 (4H, d,
Jo = 8.7 Hz, H-3, 3ꢁ, 5, 5ꢁ), 6.05 (2H, t, Jvic = 2.4 Hz,
OCH2CH=), 4.65 (4H, q, Jvic = 2.4 Hz, OCH2CH=);
13C-NMR (CDCl3): δ 190.79 (1, 1ꢁ-CHO), 163.36
(C-4, 4ꢁ), 132.02 (C-1, 1ꢁ), 130.20 (C-2, 2ꢁ, 6, 6ꢁ),
127.98 (OCH2CH=), 114.96 (C-3, 3ꢁ, 5, 5ꢁ), 67.74
(OCH2CH=); MS(ESI): m/z (M+1)+ = 297; Anal.
Calc. for C18H16O4: 5.40%; Found C, 72.91%; H,
5.46%.
2.9 Synthesis of 4,4ꢁ-[1,4-phenylenebis(methylene)]
bis(oxy)dibenzaldehyde 2bdꢁ
The bisaldehyde 2bdꢁ was prepared from the reaction of
4-hydroxybenzaldehyde (1.22 g, 0.01 mol) with α, αꢁ-
dibromo-p-xylene (1.32 g, 0.005 mol) under the similar
conditions as described above for 2aaꢁ.
2.7 Synthesis of 4,4ꢁ-[but-2-yne-1,4-diylbis(oxy)]
benzaldehyde 2bbꢁ
2bdꢁ: Cream colour solid, Yield 58%; m.p.:152–
154◦C. IR (KBr) cm−1 3071 (aromatic C-H), 2940
(methylene C-H), 2891, 2721 (aldehydic C-H), 1688
The bisaldehyde 2bbꢁ was synthesized from the reaction
of 4-hydroxybenzaldehyde (1.22 g, 0.01 mol) with 1,4-
dichloro-2-butyne (0.64 g, 0.005 mol) under the similar
conditions as described above for 2aaꢁ.
1
(C=O); H-NMR (CDCl3): δ 9.80 (2H, s, 1, 1ꢁ-CHO),
7.78 (4H, d, Jo = 8.7 Hz, H-2, 2ꢁ, 6, 6ꢁ), 7.40 (4H,
s, H-2ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 7.01 (4H, d, Jo = 8.7 Hz, H-
3, 3ꢁ, 5, 5ꢁ), 5.25 (4H, s, OCH2); 13C-NMR (CDCl3):
δ 190.24 (1, 1ꢁ-CHO), 163.09 (C-4, 4ꢁ), 135.78 (C-1,
1ꢁ), 131.48 (C-1ꢁꢁꢁꢁ, 4ꢁꢁꢁꢁ), 129.62 (C-2, 2ꢁ, 6, 6ꢁ), 127.51
(C-2ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 114.84 (C-3, 3ꢁ, 5, 5ꢁ), 69.32
(OCH2); MS(ESI): m/z (M+Na)+ = 369; Anal. Calc.
for C22H18O4: Calc. C, 76.30%; H, 5.20%; Found C,
76.26%; H, 5.16%.
2bbꢁ: Dark brown solid, Yield 61%; m.p.: 140–142◦C.
IR (KBr) cm−1 3070 (aromatic C-H), 2929 (methy-
lene C-H), 2810, 2746 (aldehydic C-H), 1678 (C=O);
1H-NMR(DMSO-d6): δ 9.88 (2H, s, 1, 1ꢁ-CHO), 7.82
(4H, dt, J = 2.6, 4.7 Hz, H-2, 2ꢁ, 6, 6ꢁ), 7.01 (4H, dt,
J = 2.6, 4.7 Hz, H-3, 3ꢁ, 5, 5ꢁ), 4.80 (4H, s, OCH2);
13C-NMR (DMSO-d6): δ 190.07 (1, 1ꢁ-CHO), 135.67

706
Mohamad Yusuf et al.
2.10 Synthesis of 4,4ꢁ-[biphenyl-4,4ꢁ-diylbis(methylene)]
bis(oxy)benzaldehyde 2beꢁ
2.12 Synthesis of 2,2ꢁ-[2,2ꢁ-{but-2-yne-1,4-diylbis(oxy)}
bis(4,1-phenylene)]bis(methan-1-yl-1-ylidene)
bis(hydrazinecarbothioamide) 3abꢁ
The bisaldehyde 2beꢁ was synthesized from the reaction
of 4-hydroxybenzaldehyde (1.22 g, 0.01 mol) with 4,4ꢁ- The bisthiosemicarbazone 3abꢁ was obtained from the
bischloromethyl-di-phenyl (1.25 g, 0.005 mol) under reaction of bisaldehyde 2aaꢁ (1.0 g, 0.0034 mol) with
the similar conditions as described above for 2aaꢁ.
thiosemicarbazide (0.61 g, 0.0068 mol) under the simi-
lar conditions as described above for 3aaꢁ.
2beꢁ: Cream solid, Yield 85%; m.p.: 225–227◦C. IR
(KBr) cm−1 3031 (aromatic C-H), 2933 (methylene 3abꢁ: Light black solid, Yield 68%; m.p.: 248–250◦C.
1
C-H), 2874, 2739 (aldehydic C-H), 1691 (C=O); H- IR (KBr) cm−1 3430, 3220, 3145 (NH), 3017 (aromatic
NMR (CDCl3): δ 9.80 (2H, s, 1, 1ꢁ-CHO), 7.78 (4H, d, C-H), 2891 (methylene C-H), 1590 (C=N), 1248, 1087
Jo = 7.8 Hz, H-2, 2ꢁ, 6, 6ꢁ), 7.58 (4H, d, Jo = 8.1 Hz, (C-O), 1162 (C=S); 1H-NMR(DMSO-d6): δ 11.40 (2H,
H-3ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁꢁ), 7.47 (4H, d, Jo = 8.1 Hz, H-2ꢁꢁꢁꢁ, s, NH-3ꢁꢁ, 3ꢁꢁꢁ), 8.60 (2H, s, H-1ꢁꢁ, 1ꢁꢁꢁ), 7.92 (2H, d,
2ꢁꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁꢁ), 7.07 (4H, d, Jo = 8.2 Hz, H-3, 3ꢁ, 5, 5ꢁ), Jo = 7.8 Hz, H-6, 6ꢁ), 7.72 (2H, brs, NH-β, βꢁ), 7.24
5.17 (4H, s, OCH2); 13C-NMR (CDCl3): δ 190.47 (1, 1ꢁ- (2H, dd, Jm,o = 1.5, 7.4 Hz, H-4, 4ꢁ), 7.46 (2H, s, NH-
1ꢁ-CHO), 163.17 (C-4, 4ꢁ), 136.05 (C-4ꢁꢁꢁꢁ, 4ꢁꢁꢁꢁꢁ), 135.78 α, αꢁ), 6.92 (4H, t, J = 8.0 Hz, H-3, 3ꢁ, 5, 5ꢁ), 5.25
(C-1, 1ꢁ), 131.57 (C-1ꢁꢁꢁꢁ, 1ꢁꢁꢁꢁꢁ), 129.02 (C-2, 2ꢁ, 6, 6ꢁ), (2H, s, OCH2); 13C-NMR (DMSO-d6): δ 177.84 (C-4ꢁꢁ,
126.71 (C-3ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁꢁ), 126.54 (C-2ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ, 4ꢁꢁꢁ), 157.64 (C-2, 2ꢁ), 138.30 (C-1ꢁꢁ, 1ꢁꢁꢁ), 130.19 (C-
6ꢁꢁꢁꢁꢁ), 115.00 (C-3, 3ꢁ, 5, 5ꢁ), 69.02 (OCH2); MS(ESI): 4, 4ꢁ), 4ꢁ), 125.98 (C-6, 6ꢁ), 122.43 (C-5, 5ꢁ), 120.21
m/z (M+1)+ = 423; Anal. Calc. for C28H22O4: Calc. C, (C-1, 1ꢁ), 112.32 (C-3, 3ꢁ), 82.50 (C-1ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁꢁ), 62.61
79.62%; H, 5.21%; Found C, 79.53%; H, 5.26%.
(OCH2CH=); MS(ESI): m/z (M+1)+ = 441; Anal.
Calc. for C20H20N6S2O2: Calc. C, 54.54%; H, 4.54%;
N, 19.09%, S, 14.54%; Found C, 54.50%; H, 4.49%; N,
19.02%, S, 14.59%.
2.11 Synthesis of 2,2ꢁ-[2,2ꢁ-{but-2-ene-1,4-diylbis(oxy)}
bis(4,1-phenylene)]bis(methan-1-yl-1-ylidene)
bis(hydrazinecarbothioamide) 3aaꢁ
2.13 Synthesis of 2,2ꢁ-[2,2ꢁ-{1,2-phenylenebis
(methylene)}bis(oxy)bis(2,1-phenylene)]bis(methan-1-
yl-1-ylidene) bis(hydrazinecarbothioamide) 3acꢁ
A mixture of bisaldehyde 2aaꢁ (1.0 g, 0.0034 mol) and
thiosemicarbazide (0.61 g, 0.0068 mol) in dry EtOH
(20 ml) and HCl (1.0 ml) was refluxed for 4 h. After
cooling of the reaction mixture in an ice bath, a solid
was separated out. The resulting product was filtered
under suction and crystallised from MeOH to yield pure
bisthiosemicarbazone 3aaꢁ.
The bisthiosemicarbazone 3acꢁ was synthesised from
the reaction of bisaldehyde 2acꢁ (1.0 g, 0.0029 mol)
with thiosemicarbazide (0.52 g, 0.0058 mol) under the
similar conditions as described above for 3aaꢁ.
3aaꢁ: Light brown solid, Yield 78%; m.p.: 228–230◦C.
IR (KBr) cm−1 3402, 3225, 3145 (NH), 3016 (aromatic
C-H), 2890 (methylene C-H) 1599 (C=N), 1250, 1089
(C-O), 1160 (C=S); 1H-NMR(DMSO-d6): δ 11.40 (2H,
s, NH-3ꢁꢁ, 3ꢁꢁꢁ), 8.52 (2H, s, H-1ꢁꢁ, 1ꢁꢁꢁ), 7.90 (2H, d,
Jo = 7.8 Hz, H-6, 6ꢁ), 7.80 (2H, brs, NH-β, βꢁ), 7.26
(2H, dd, Jm,o = 1.5, 7.4 Hz, H-4, 4ꢁ), 7.48 (2H, s,
NH-α, αꢁ), 6.90 (4H, t, Jo = 8.0 Hz, H-3, 3ꢁ, 5, 5ꢁ),
6.16 (2H, s, OCH2CH=), 4.61 (4H, s, OCH2CH=);
13C-NMR (DMSO-d6): δ 177.80 (C-4ꢁꢁ, 4ꢁꢁꢁ), 156.64
(C-2, 2ꢁ), 138.18 (C-1ꢁꢁ, 1ꢁꢁꢁ), 130.99 (C-4, 4ꢁ), 127.11
(OCH2CH=), 125.98 (C-6, 6ꢁ), 122.43 (C-5, 5ꢁ),
120.62 (C-1, 1ꢁ), 112.42 (C-3, 3ꢁ), 67.56 (OCH2CH=);
MS(ESI): m/z (M+Na)+ = 465; Anal. Calc. for
C20H22N6S2O2: Calc. C, 52.30%; H, 4.98%; N, 19.00%,
S, 14.48%; Found C, 52.37%; H, 4.90%; N, 19.06%, S,
14.554%.
3acꢁ: Yellow solid, Yield 78%; m.p.: 219–221◦C. IR
(KBr) cm−1 3363, 3247, 3154 (N-H), 3020 (aromatic
C-H), 2865 (methylene C-H), 1597 (C=N), 1254, 1086
1
(C–O), 1160 (C=S); H-NMR (DMSO-d6): δ 11.46
(2H, s, NH-3ꢁꢁ, 3ꢁꢁꢁ), 8.54 (2H, s, H-1ꢁꢁ, 1ꢁꢁꢁ), 8.02 (2H,
dd, Jp,o = 0.9, 7.6 Hz, H-6, 6ꢁ), 7.97 (2H, brs, NH-β,
βꢁ), 7.65 (2H, brs, NH-α, αꢁ), 7.63 (2H, td, 7.63 (2H,
td, J = 3.6, 5.2 Hz, H-3ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 7.40 (2H, td, J = 3.3,
5.5 Hz, H-4ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ), 7.30 (2H, td, Jm,o = 1.4, 8.5 Hz,
H-4, 4ꢁ), 7.06 (2H, d, Jo = 8.4 Hz, H-5, 5ꢁ), 6.92 (2H,
t, Jo = 7.5 Hz, H-3, 3ꢁ), 5.27 (4H, s, OCH2); 13C-
NMR (DMSO-d6): δ 177.84 (C-4ꢁꢁ, 4ꢁꢁꢁ), 159.55 (C-2,
2ꢁ), 143.00 (C-1ꢁꢁ, 1ꢁꢁꢁ), 132.11 (C-1ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁ), 130.96 (C-
4, 4ꢁ), 127.90 (C-3ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 127.41 (C-2ꢁꢁꢁꢁ, 4ꢁꢁꢁꢁ), 125.72
(C-6, 6ꢁ), 121.20 (C-5, 5ꢁ), 116.90 (C-1, 1ꢁ), 114.47 (C-
3, 3ꢁ), 65.20 (OCH2); MS(ESI): m/z (M+Na)+ = 515;
Anal. Calc. for C20H22N6S2O2: Calc. C, 58.54%; H,

Synthesis of bisthiadiazolines
707
4.88%; N, 17.07%, S, 13.00%; Found C, 58.49%; H, 1ꢁ38.28 (C-4ꢁꢁꢁꢁ, 4ꢁꢁꢁꢁꢁ), 135.88 (C-1ꢁꢁꢁꢁ, 1ꢁꢁꢁꢁꢁ), 130.96 (C-4,
4.94%; N, 17.12%, S, 13.08%.
4 ), 127.86 (C-3, 3ꢁ), 126.69 (C-6, 6ꢁ), 126.73 (C-3ꢁꢁꢁꢁ,
3ꢁꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁꢁ), 126.54 (C-2ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁꢁ), 122.43
(C-5, 5ꢁ) 120.75 (C-1, 1ꢁ), 112.73 (C-3, 3ꢁ), 69.31
(OCH2); MS(ESI): m/z (M+1)+ = 569; Anal. Calc. for
C30H28N6S2O2: Calc. C, 63.38%; H, 4.93%; N, 14.79%,
S, 11.27%; Found C, 63.30%; H, 4.98%; N, 14.84%, S,
11.20%.
2.14 Synthesis of 2,2ꢁ-[2,2ꢁ-{1,4-phenylenebis
(methylene)bis(oxy)bis(2,1-phenylene) bis(methan-1-
yl-1-ylidene)bis(hydrazinecarbothioamide) 3adꢁ
The bisthiosemicarbazone 3adꢁ was prepared from the
reaction of bisaldehyde 2adꢁ (1.0 g, 0.0029 mol) with
thiosemicarbazide (0.52 g, 0.0058 mol) under the simi-
lar conditions as described above for 3aaꢁ.
2.16 Synthesis of 2,2ꢁ-[4,4ꢁ-{but-2-ene-1,4-diylbis
(oxy)}bis(4,1-phenylene)]bis(methan-1-yl-1-ylidene)
bis(hydrazinecarbothioamide) 3baꢁ
3adꢁ: Yellow solid, Yield 78%; m.p.: 226–228◦C. IR
(KBr) cm−1 3363, 3247, 3154 (N-H), 3020 (aromatic
C-H), 2865 (methylene C-H), 1597 (C=N), 1237, 1107
(C-O), 1160 (C=S); 1H-NMR(DMSO-d6): δ 11.49 (2H,
s, NH- 3ꢁꢁ, 3ꢁꢁꢁ), 8.60 (2H, s, H-1ꢁꢁ, 1ꢁꢁꢁ), 7.92 (2H, d,
J = 7.6 Hz, H-6, 6ꢁ), 7.67 (2H, s, NH-β, βꢁ), 7.54
(4H, s, H-2ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 7.47 (2H, s, NH-α, αꢁ),
7.35 (2H, t, Jo = 8.1 Hz, H-4, 4ꢁ), 7.02 (2H, d, J =
8.3 Hz, H-5, 5ꢁ), 6.97 (2H, t, J = 7.5 Hz, H-3, 3ꢁ),
5.16ꢁꢁ(4H, s, OCH2); 13C-NMR (DMSO-d6): δ 177.82
(C-4 , 4ꢁꢁꢁ), 157.65 (C-2, 2ꢁ), 140.65 (C-1ꢁꢁ, 1ꢁꢁꢁ), 138.23
(C-1ꢁꢁꢁꢁ, 4ꢁꢁꢁꢁ), 130.96 (C-4, 4ꢁ), 129.82 (C-6, 6ꢁ), 127.40
(C-2ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 122.40 (C-5, 5ꢁ), 112.73 (C-3, 3ꢁ),
69.31 (OCH2); MS(ESI): m/z (M+Na)+ = 515; Anal.
Calc. for C20H22N6S2O2: Calc. C, 58.54%; H, 4.88%;
N, 17.07%, S, 13.00%; Found C, 58.59%; H, 4.82%; N,
17.00%, S, 13.10%.
The bisthiosemicarbazone 3baꢁ was prepared from the
reaction of bisaldehyde 2baꢁ (1.0 g, 0.0033 mol) with
thiosemicarbazide (0.61 g, 0.0067 mol) under the simi-
lar conditions as described above for 3aaꢁ.
3baꢁ: Light brown solid, Yield 82%; m.p.: 222–224◦C.
IR (KBr) cm−1 3342, 3264, 3159 (NH), 3071 (aro-
matic C-H), 2921, 2863 (methylene C-H), 1602 (C=N),
1246, 1080 (C–O), 1167 (C=S); 1H-NMR (DMSO-d6):
δ 11.26 (2H, s, NH-3ꢁꢁ, 3ꢁꢁꢁ), 7.95 (2H, s, H-1ꢁꢁ, 1ꢁꢁꢁ), 7.62
(2H, brs, NH-β, βꢁ), 7.56 (4H, d, Jo = 8.6 Hz, H-2,
2ꢁ, 6, 6ꢁ), 7.47 (4H, s, NH-α, αꢁ), 6.85 (4H, d, Jo =
8.5 Hz, H-3, 3ꢁ, 5, 5ꢁ), 6.02 (4H, t, OCH2CH=), 4.57
(4H, d, OCH2CH=); 13C-NMR (DMSO-d6): δ 177.62
(C-4ꢁꢁ, 4ꢁꢁꢁ), 159.47 (C-4, 4ꢁ), 142.37 (C-1ꢁꢁ, 1ꢁꢁꢁ), 128.54
(C-1, 1ꢁ), 127.76 (OCH2CH=), 126.69 (C-2, 2ꢁ, 6, 6ꢁ),
114.52 (C-3, 3ꢁ, 5, 5ꢁ), 67.15 (OCH2CH=); MS(ESI):
m/z (M+Na)+ = 465; Anal. Calc. for C20H22N6S2O2:
Calc. C, 52.30%; H, 4.98%; N, 19.00%, 14.48%; Found
C, 52.35%; H, 4.93%; N, 19.06%, 14.40%.
2.15 Synthesis of 2,2ꢁ-[2,2ꢁ-{biphenyl-4,4ꢁ-diylbbis
(methylene)}bis(oxy)bis(4,1-phenylene)bis(methan-1-
yl-1-ylidene)bis(hydrazinecarbothioamide) 3aeꢁ
2.17 Synthesis of 2,2ꢁ-[4,4ꢁ-{but-2-yne-1,4-diylbis(oxy)}
bis(4,1-phenylene)]bis(methan-1-yl-1-ylidene)
bis(hydrazinecarbothioamide) 3bbꢁ
The bisthiosemicarbazone 3aeꢁ was prepared from the
reaction of bisaldehyde 2aeꢁ (1.0 g, 0.0023 mol) with
thiosemicarbazide (0.43 g, 0.0047 mol) under the simi-
lar conditions as described above for 3aaꢁ.
The bisthiosemicarbazone 3bbꢁ was prepared from the
reaction of bisaldehyde 2bbꢁ (1.0 g, 0.0032 mol) with
thiosemicarbazide (0.61 g, 0.0068 mol) under the simi-
lar conditions as described above for 3aaꢁ.
3aeꢁ: Yellow solid, Yield 74%; m.p.: 236–238◦C. IR
(KBr) cm−1 3420, 3291, 3153 (NH), 3060 (aromatic
C-H), 2980 (methylene C-H), 1598 (C=N), 1253, 1082 3bbꢁ: Brown solid, Yield 80%; m.p.: 238–240◦C. IR
1
(C-O), 1162 (C=S); H-NMR (DMSO-d6): δ 11.50 (KBr) cm−1 3499, 3381, 3152 (NH), 1602 (C=N),
(2H, s, NH-3ꢁꢁ, 3ꢁꢁꢁ), 8.60 (2H, s, H-1ꢁꢁ, 1ꢁꢁꢁ), 8.18 (2H, 1232, 1089 (C-O), 1168 (C=S); H-NMR(DMSO-d6):
1
s, NH-β, βꢁ), 8.08 (2H, dd, J = 1.6, 7.8 Hz, H-6, 6ꢁ), δ 11.32 (2H, s, 3, 3ꢁ-NH), 8.01 (2H, brs, NH-β, βꢁ), 7.96
7.78 (2H, s, NH-α, αꢁ), 7.70 (4H, d, Jo = 8.3 Hz, H- (2H, s, H-1ꢁꢁ, 1ꢁꢁꢁ), 7.66 (4H, d, J = 8.4 Hz, H-2, 2ꢁ, 6,
3ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁꢁ), 7.61 (4H, d, Jo = 8.3 Hz, H-2ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ, 6ꢁ), 7.64 (2H, s, NH-α, αꢁ), 6.94 (4H, d, J = 8.8 Hz, H-
6ꢁꢁꢁꢁꢁ), 7.36 (2H, td, Jm,o = 1.7, 8.6 Hz, H-4, 4ꢁ), 7.15 3, 3ꢁ, 5, 5ꢁ), 4.82 (4H, s, OCH2); 13C-NMR (DMSO-d6):
(2H, d, Jo = 8.3 Hz, H-5, 5ꢁ), 6.97 (2H, t, J = 7.5 Hz, δ 177.67 (C-4ꢁꢁ, 4ꢁꢁꢁ), 158.44 (C-4, 4ꢁ), 142.17 (C-1ꢁꢁ, 1ꢁꢁꢁ),
H-3, 3ꢁ), 5.21 (4H, s, OCH2); 13C-NMR (DMSO-d6): 128.46 (C-2, 2ꢁ, 6, 6ꢁ), 127.26 (C-1, 1ꢁ), 114.72 (C-3, 3ꢁ,
177.82 (C-4ꢁꢁ, 4ꢁꢁꢁ), 156.79 (C-2, 2ꢁ), 139.42 (C-1ꢁꢁ, 1ꢁꢁꢁ), 5, 5ꢁ), 82.05 (C-1ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁ), 55.51 (OCH2); MS(ESI): m/z

708
Mohamad Yusuf et al.
(M+Na)+ = 463; Anal. Calc. for C20H20N6S2O2: Calc. Calc. for C20H22N6S2O2: Calc. C, 58.54%; H, 4.88%;
C, 54.54%; H, 4.54%; N, 19.09%, S, 14.54%; Found C, N, 17.07%, S, 13.00%; Found C, 58.61%; H, 4.82%; N,
54.50%; H, 4.48%; N, 19.02%, S, 14.60%.
17.00%, S, 12.93%.
2.18 Synthesis of 2,2ꢁ-[4,4ꢁ-{1,2-phenylenebis
(methylene)}bis(oxy)bis(4,1-phenylene)]bis(methan-1-
yl-1-ylidene)bis(hydrazinecarbothioamide) 3bcꢁ
2.20 Synthesis of 2,2ꢁ-[4,4ꢁ-{biphenyl-4,4ꢁ-diylbbis
(methylene)}bis(oxy)bis(4,1-phenylene)bis(methan-1-
yl-1-ylidene)bis(hydrazinecarbothioamide) 3beꢁ
The bisthiosemicarbazone 3bcꢁ was obtained from the
reaction of bisaldehyde 2bcꢁ (1.0 g, 0.0029 mol) with
thiosemicarbazide (0.52 g, 0.0058 mol) under the simi-
lar conditions as described above for 3aaꢁ.
The bisthiosemicarbazone 3beꢁ was prepared from the
reaction of bisaldehyde 2beꢁ (1.0 g, 0.0023 mol) with
thiosemicarbazide (0.43 g, 0.0047 mol) under the simi-
lar conditions as described above for 3aaꢁ.
3bcꢁ: Yellow solid, Yield 79%; m.p.: 219–221◦C. IR
(KBr) cm−1 3410, 3254, 3150 (NH), 3013 (aromatic
C-H), 2915, 2854 (methylene C-H), 1602 (C=N),
3beꢁ: Yellow solid, Yield 74%; m.p.: 285–287◦C. IR
(KBr) cm−1 3410, 3250, 3150 (NH), 3061 (aromatic C-
H), 2933, 2874 (methylene C-H), 1601 (C=N), 1239
1
1248, 1097 (C-O), 1167 (C=S); H-NMR(DMSO-d6):
1
and 1081 (C-O), 1168 (C=S); H-NMR(DMSO-d6): δ
δ 11.26 (2H, s, NH-3ꢁꢁ, 3ꢁꢁꢁ), 7.93 (2H, s, H-1ꢁꢁ, 1ꢁꢁꢁ), 7.72
(2H, brs, NH-β, βꢁ), 7.55 (4H, d, Jo = 8.4 Hz, H-2, 2ꢁ,
6, 6ꢁ), 7.43 (4H, brs, H-3ꢁꢁꢁꢁ, 4ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 7.29 (2H, brs,
NH-α, αꢁ), 6.89 (4H, d, Jo = 8.4 Hz, H-3, 3ꢁ, 5, 5ꢁ), 5.13
(4H, s, OCH2); 13C-NMR (DMSO-d6): δ 177.62 (C-4ꢁꢁ,
4ꢁꢁꢁ), 159.47 (C-4, 4ꢁ) 142.47 (C-1ꢁꢁ, 1ꢁꢁꢁ), 132.04 (C-1ꢁꢁꢁꢁ,
2ꢁꢁꢁꢁ), 131.48 (C-1, 1ꢁ), 128.54 (C-2, 2ꢁ, 6, 6ꢁ), 127.76
(C-3ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 127.27 (C-4ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ), 114.52 (C-3, 3ꢁ, 5, 5ꢁ),
67.15 (OCH2); MS(ESI): m/z (M+1)+ = 493; Anal.
Calc. for C20H22N6S2O2: Calc. C, 58.54%; H, 4.88%;
N, 17.07%, S, 13.00%; Found C, 58.60%; H, 4.94%; N,
17.12%, S, 13.06%.
11.30 (2H, s, NH), 8.06 (2H, s, H-1ꢁꢁ, 1ꢁꢁꢁ), 7.97 (2H,
brs, NH-β, βꢁ), 7.66 (4H, d, Jo = 8.4 Hz, H-2, 2ꢁ, 6,
6ꢁ), 7.64 (2H, s, NH-α, αꢁ), 7.60 (4H, d, Jo = 8.6 Hz,
H-3ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁꢁ, 5ꢁꢁꢁꢁꢁ), 7.48 (4H, d, Jo = 8.0 Hz, H-
2ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁꢁ), 6.97 (4H, d, Jo = 8.6 Hz, H-3, 3ꢁ,
5, 5ꢁ), 5.12 (4H, s, OCH2); 13C-NMR (DMSO-d6): δ
177.62 (C-4ꢁꢁ, 4ꢁꢁꢁ), 159.66 (C-4, 4ꢁ), 142.19 (C-1ꢁꢁ, 1ꢁꢁꢁ),
139.45 (C-4ꢁꢁꢁꢁ, 4ꢁꢁꢁꢁꢁ), 135.80 (C-1ꢁꢁꢁꢁ, 1ꢁꢁꢁꢁꢁ), 128.68 (C-1,
1ꢁ), 127.82 (C-3ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁꢁꢁ), 126.89 (C-2ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁꢁ,
6ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁꢁ), 126.63 (C-2, 2ꢁ, 6, 6ꢁ), 114.73 (C-3, 3ꢁ, 5, 5ꢁ),
69.03 (OCH2); MS(ESI): m/z (M+Na)+ = 591; Anal.
Calc. for C30H28N6S2O2: Calc. C, 63.38%; H, 4.93%;
N, 14.79%, S, 11.27%; Found C, 63.44%; H, 4.98%; N,
14.72%, S, 11.34%.
2.19 Synthesis of 2,2ꢁ-[4,4ꢁ-{1,4-phenylenebis
(methylene)bis(oxy)bis(4,1-phenylene) bis(methan-1-
yl-1-ylidene)bis(hydrazinecarbothioamide) 3bdꢁ
2.21 Synthesis of N,Nꢁ-[5,5ꢁ-{2,2ꢁ-(but-2-ene-1,4-
diylbis(oxy))bis(2,1-phenylene)]bis(4-acetyl-4,5-
dihydro-1,3,4-thiadiazole-5,2-diyl)]diacetamide 4aaꢁ
The bisthiosemicarbazone 3bdꢁ was prepared from the
reaction of bisaldehyde 2bdꢁ (1.0 g, 0.0028 mol) with
thiosemicarbazide (0.52 g, 0.0057 mol) under the simi-
lar conditions as described above for 3aaꢁ.
A mixture of bisthiosemicarbazone (1.0 g, 0.0023 mol)
and acetic anhydride (30 ml) was refluxed for 10 h. The
progress of reaction was monitored by TLC. The result-
ing reaction mixture was poured over ice to obtain
a solid product which was filtered under suction and
finally crystallized from EtOH to yield pure bisthiadia-
zoline 4aaꢁ.
3bdꢁ: Yellow solid, 84%; m.p.: 250–252◦C. IR (KBr)
cm−1 3346, 3280, 3154 (NH), 3013 (aromatic C-H),
2913, 2855 (methylene C-H), 1602 (C=N), 1235 and
1079 (C-O), 1170 (C=S);1H-NMR (DMSO-d6): δ
11.26 (2H, s, NH-3ꢁꢁ, 3ꢁꢁꢁ), 7.94 (2H, s, H-1ꢁꢁ, 1ꢁꢁꢁ), 7.62
(2H, brs, NH-β, βꢁ), 7.56 (4H, d, Jo = 8.6 Hz, H-2, 2ꢁ,
6, 6ꢁ), 7.39 (4H, s, H-2ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 7.36 (2H, brs,
NH-α, αꢁ), 6.90 (4H, d, Jo = 8.4 Hz, H-3, 3ꢁ, 5, 5ꢁ),
5.12 (4H, s, OCH2); 13C-NMR (DMSO-d6): δ 177.64
(C-4, 4ꢁ), 159.63 (C-4ꢁꢁ, 4ꢁꢁꢁ), 142.47 (C-1ꢁꢁ, 1ꢁꢁꢁ), 131.48
(C-1, 1ꢁ), 128.49 (C-1ꢁꢁꢁꢁ, 4ꢁꢁꢁꢁ), 127.41 (C-2, 2ꢁ, 6, 6ꢁ),
126.71 (C-2ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 114.64 (C-3, 3ꢁ, 5, 5ꢁ),
69.08 (OCH2); MS(ESI): m/z (M+Na)+ = 515; Anal.
4aaꢁ: White solid, Yield 80%; m.p.: 170–172◦C. IR
(KBr) cm−1 3221 (C=C), 3064 (N-H), 2950, 2936
(methylene C-H), 1687, 1639 (C=O), 1603 (C=N),
1
1238 and 1106 (C-O); H-NMR(DMSO-d6): δ 11.53
(2H, s, NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 8.03 (2H, brs, H-6, 6ꢁ),
7.27 (2H, m, H-4, 4ꢁ), 7.00 (2H, d, J = 8.1 Hz, H-
5, 5ꢁ), 6.90 (2H, d, J = 6.8 Hz, H-3, 3ꢁ), 6.88 (2H, s,

Synthesis of bisthiadiazolines
709
H-2ꢁꢁ, 2ꢁꢁꢁ), 6.15 (2H, brs, OCH2CH=), 4.72 (4H, brs, 1687, 1639 (C=O), 1603 (C=N), 1238, 1106 (C-O);
OCH2CH=), 2.26 (6H, s, COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 2.02 (6H, s, 1H-NMR (DMSO-d6): δ 11.50 (2H, s, NHCOCH3- 5ꢁꢁ,
NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ); 13C-NMR (DMSO-d6): δ 169.00 5ꢁꢁꢁ), 7.96 (2H, brs, H-6, 6ꢁ), 7.62 (2H, m, H-2ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ),
(NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 167.49 (COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 153.71 7.36 (2H, m, H-3ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ), 7.30 (2H, d, Jo = 8.0 Hz, H-
(C-2, 2ꢁ), 147.78 (C-5ꢁꢁ, 5ꢁꢁꢁ), 128.95 (C-1, 1ꢁ), 128.19 4, 4ꢁ), 7.06 (4H, d, J = 8.0 Hz, H-3, 3ꢁ, 5, 5ꢁ), 6.92
(C-5, 5ꢁ), 127.54 (OCH2CH=), 123.90 (C-6, 6ꢁ), 120.36 (2H, d, Jo = 4.9 Hz, H-3ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 6.89 (2H, s, H-2ꢁꢁ, 2ꢁꢁꢁ),
(C-4, 4ꢁ), 111.81 (C-3, 3ꢁ), 67.50 (OCH2CH=), 61.79 5.30 (4H, s, OCH2), 2.28 (6H, s, COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 2.06
(C-2ꢁꢁ, 2ꢁꢁꢁ), 22.37 (NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 21.68 (COCH3– (6H, s, NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ); 13C-NMR (DMSO-d6): δ
3ꢁꢁ, 3ꢁꢁꢁ); MS(ESI): m/z (M+Na)+ = 633; Anal. Calc. 168.85 (5ꢁꢁ, 5ꢁꢁꢁ-NHCOCH3), 168.69 (3ꢁꢁ, 3ꢁꢁꢁ-COCH3),
for C28H30O6N6S2: Calc. C, 55.08%; H, 4.91%, N, 15ꢁꢁꢁ3ꢁ .71 (C-2, 2ꢁ), 148.04 (C-5ꢁꢁ, 5ꢁꢁꢁ), 130.95 (C-1ꢁꢁꢁꢁ,
13.77%; S, 10.49%; Found C, 55.00%; H, 4.96%, N, 2 ), 129.63 (C-1, 1ꢁ), 128.52 (C-5, 5ꢁ), 127.88 (C-3ꢁꢁꢁꢁ,
13.82%; S, 10.54%.
6ꢁꢁꢁꢁ), 127.56 (C-4ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ), 123.70 (C-6, 6ꢁ), 120.42 (C-
4, 4ꢁ), 112.40 (C-3, 3ꢁ), 69.79 (OCH2), 67.09 (C-2ꢁꢁ,
2ꢁꢁꢁ), 22.02 (NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 20.78 (COCH3—3ꢁꢁ,
3ꢁꢁꢁ); MS(ESI): m/z (M+1)+ = 661; Anal. Calc. for
C32H32O6N6S2: Calc. C, 58.18%; H, 4.85%, N, 12.73;
S, 9.69%; Found C, 58.23%; H, 4.89%, N, 12.76; S,
9.74%.
2.22 Synthesis of N,Nꢁ-[5,5ꢁ-{2,2ꢁ-(but-2-yne-1,4-
diylbis(oxy))bis(2,1-phenylene)]bis(4-acetyl-4,5-
dihydro-1,3,4-thiadiazole-5,2-diyl)]diacetamide 4abꢁ
The compound 4abꢁ was synthesized by refluxing bis-
thiosemicarbazone 3abꢁ (1.0 g, 0.0023 mol) with acetic
anhydride (30 ml) under the similar conditions as de-
scribed above for 4aaꢁ.
2.24 Synthesis of N,Nꢁ-[5,5ꢁ-{2,2ꢁ-(1,4-phenylenebis
(methylene)}bis(oxy)bis(2,1-phenylene)]bis(4-acetyl-4,
5-dihydro-1,3,4-thiadiazole-5,2-diyl)]diacetamide 4adꢁ
4abꢁ: Brown solid, Yield 60%; m.p.: 230–232◦C. IR
(KBr) cm−1 3062 (N-H), 2934, 2931 (methylene C–H),
1685, 1632 (C=O), 1604 (C=N), 1238 and 1108 (C-
The compound 4adꢁ was prepared by refluxing bis-
thiosemicarbazone 3adꢁ (1.0 g, 0.0020 mol) with acetic
anhydride (30 ml) under the similar conditions as de-
scribed above for 4aaꢁ.
1
O); H-NMR(DMSO-d6): δ 11.43 (2H, s, NHCOCH3-
5ꢁꢁ, 5ꢁꢁꢁ), 8.04 (2H, brs, H-6, 6ꢁ), 7.25 (2H, m, H-4,
4ꢁ), 7.02 (2H, d, J = 8.1 Hz, H-5, 5ꢁ), 6.92 (2H, d,
J = 6.8 Hz, H-3, 3ꢁ), 6.86 (2H, s, H-2ꢁꢁ, 2ꢁꢁꢁ), 5.12 (4H,
s, OCH2), 2.26 (6H, s, COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 2.12 (6H, s,
NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ); 13C-NMR (DMSO-d6): δ 169.21
(NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 167.44 (COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 153.24
(C-2, 2ꢁ), 146.78 (C-5ꢁꢁ, 5ꢁꢁꢁ), 128.92 (C-1, 1ꢁ), 128.02
(C-5, 5ꢁ), 123.92 (C-6, 6ꢁ), 120.11 (C-4, 4ꢁ), 112.11
(C-3, 3ꢁ), 81.96 (C-1ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁ), 66.50 (OCH2), 61.79 (C-
2ꢁꢁ, 2ꢁꢁꢁ), 22.37 (NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 21.73 (COCH3–3ꢁꢁ,
3ꢁꢁꢁ); MS(ESI): m/z (M+Na)+ = 631; Anal. Calc. for
C28H28N6O6S2: C, 55.26%; H, 8.33%; N, 13.81%; S,
10.52%; Found C, 55.22%; H, 8.38%; N, 13.77%; S,
10.48%.
4adꢁ: White solid, Yield 80%; m.p.: 118–120◦C. IR
(KBr) cm−1 3066 (N-H), 2950, 2931 (methylene C-H),
1689 and 1663 (C=O), 1601 (C=N), 1238 and 1010 (C-
O); 1H-NMR (DMSO-d6): δ 11.54 (2H, s, NHCOCH3–
5ꢁꢁ, 5ꢁꢁꢁ), 7.96 (2H, brs, H-6, 6ꢁ), 7.47 (4H, brs, H-2ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁ,
5ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 7.35 (2H, d, Jo = 7.96 Hz, H-4, 4ꢁ), 6.94 (4H,
t, J = 7.5 Hz, H-3, 3ꢁ, 5, 5ꢁ), 6.90 (2H, s, H-2ꢁꢁ, 2ꢁꢁꢁ), 5.21
(4H, s, OCH2), 2.12 (6H, s, COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 2.08 (6H,
s, NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ); 13C-NMR (DMSO-d6): δ 170.92
(NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 168.97 (COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 154.71
(C-2, 2ꢁ), 148.07 (C-5ꢁꢁ, 5ꢁꢁꢁ), 130.75 (C-1ꢁꢁꢁꢁ, 4ꢁꢁꢁꢁ), 128.95
(C-1, 1ꢁ) 128.66 (C-2ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 128.19 (C-5, 5ꢁꢁ),
123.90 (C-6, 6ꢁ), 120.36 (C-4, 4ꢁ), 112.34 (C-3, 3 ),
68.08 (OCH2), 67.08 (C-2ꢁꢁ, 2ꢁꢁꢁ), 21.96 (NHCOCH3–5ꢁꢁ,
5ꢁꢁꢁ), 20.68 (COCH3–3ꢁꢁ, 3ꢁꢁꢁ); MS(ESI): m/z (M+1)+ =
661; Anal. Calc. for C32H32O6N6S2: Calc. C, 58.18%;
H, 4.85%, N, 12.73; S, 9.69%; Found C, 58.23%; H,
4.89%, N, 12.70; S, 9.63%.
2.23 Synthesis of N,Nꢁ-[5,5ꢁ-{2,2ꢁ-(1,2-phenylenebis
(methylene)}bis(oxy)bis(2,1-phenylene)]bis(4-acetyl-4,
5-dihydro-1,3,4-thiadiazole-5,2-diyl)]diacetamide 4acꢁ
The compound 4acꢁ was synthesized by refluxing bis-
thiosemicarbazone 3acꢁ (1.0 g, 0.0020 mol) with acetic
anhydride (30 ml) under the similar conditions as de-
scribed above for 4aaꢁ.
2.25 Synthesis of N,Nꢁ-[5,5ꢁ-{2,2ꢁ-(biphenyl-4,4ꢁ-diylbis
(methylene)}bis(oxy)bis(2,1-phenylene)]bis(4-acetyl-4,
5-dihydro-1,3,4-thiadiazole-5,2-diyl)]diacetamide 4aeꢁ
4acꢁ: White solid, Yield 70%; m.p.: 120–123◦C. IR The compound 4aeꢁ was obtained by refluxing bis-
(KBr) cm−1 3064 (N-H), 2950, 2936 (methylene C-H), thiosemicarbazone 3aeꢁ (1.0 g, 0.0017 mol) with acetic

710
Mohamad Yusuf et al.
anhydride (30 ml) under the similar conditions as de- 2.27 Synthesis of N,Nꢁ-[5,5ꢁ-{4,4ꢁ-(but-2-yne-1,4-
scribed above for 4aaꢁ.
diylbis(oxy))bis(4,1-phenylene)]bis(4-acetyl-4,5-
dihydro-1,3,4-thiadiazole-5,2-diyl)]diacetamide 4bbꢁ
4aeꢁ: Light brown solid, Yield 60%; m.p.: 160–162◦C.
The compound 4bbꢁ was obtained by refluxing bis-
thiosemicarbazone 3bbꢁ (1.0 g, 0.0024 mol) with acetic
anhydride (30 ml) under the similar conditions as de-
scribed above for 4aaꢁ.
3066 (N-H), 2950, 2931 (methylene C-H), 1689, 1663
1
(C=O), 1601 (C=N), 1238, 1010 (C-O); H-NMR
(CDCl3): δ 11.50 (2H, s, NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 7.96 (2H,
d, J = 4.5 Hz, H-6, 6ꢁ), 7.68 (2H, d, J = 8.2 Hz, H-
3ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁꢁ), 7.57 (4H, d, J = 8.2 Hz, H-2ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁꢁ,
6ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁꢁ), 7.25 (2H, td, J = 6.4, 8.4 Hz, H-4, 4ꢁ), 7.05
(2H, d, Jo = 8.2 Hz, H-3, 3ꢁ, 5, 5ꢁ), 6.96 (2H, s, H-2ꢁꢁ,
2ꢁꢁꢁ), 6.93 (2H, 2ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁꢁ, 4ꢁꢁꢁꢁ, 4ꢁꢁꢁꢁꢁ), 5.23 (OCH2), 2.28
(6H, s, COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 2.06 (6H, s, NHCOCH3–5ꢁꢁ,
5ꢁꢁꢁ); 13C-NMR (DMSO-d6): δ 169.15 (NHCOCH3–5ꢁꢁ,
5ꢁꢁꢁ), 167.63 (COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 153.74 (C-2, 2ꢁ), 147.71
(C-5ꢁꢁ, 5ꢁꢁꢁ), 139.51 (C-4ꢁꢁꢁꢁ, 4ꢁꢁꢁꢁꢁ), 135.53 (C-1ꢁꢁꢁꢁ, 1ꢁꢁꢁꢁꢁ),
129.00 (C-1, 1ꢁ), 128.24 (C-5, 5ꢁ), 127.57 (C-3ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁꢁ,
5ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁꢁ), 126.71 (C-2ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁꢁ), 123.96 (C-6, 6ꢁ),
120.46 (C-4, 4ꢁ), 111.83 (C-3, 3ꢁ), 69.23 (OCH2), 61.68
(C-2ꢁꢁ, 2ꢁꢁꢁ), 22.39 (NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 21.64 (COCH3–
3ꢁꢁ, 3ꢁꢁꢁ); MS(ESI): m/z (M+Na)+ = 759; Anal. Calc.
for C38H36O6N6S2: Calc. C, 61.96%; H, 4.89%, N,
11.41%; S, 8.69%; Found C, 61.90%; H, 4.82%, N,
11.35%; S, 8.61%.
4bbꢁ: Black solid, Yield 60%; m.p.:130–132◦C. IR
(KBr) cm−1 3060 (NH), 2940, 2915 (methylene C-H),
1673, 1630 (C=O), 1605 (C=N), 1238, 1033 (C-O);
1H-NMR (DMSO-d6): δ 11.35 (2H, s, NHCOCH3–5ꢁꢁ,
5ꢁꢁꢁ), 7.66 (2H, s, H-2ꢁꢁ, 2ꢁꢁꢁ), 7.32 (2H, d, Jo = 8.2 Hz,
H-2, 2ꢁ, 6, 6ꢁ), 6.94 (2H, d, Jo = 8.5 Hz, H-3, 3ꢁ,
5, 5ꢁ), 4.80 (4 H, s, OCH2), 2.15 (6H, s, COCH3–
3ꢁꢁ, 3ꢁꢁꢁ), 2.11 (6H, s, NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ); 13C-NMR
(DMSO-d6): δ 169.02 (NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 167.18
(COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 157.89 (C-4, 4ꢁ), 146.06 (C-5ꢁꢁ, 5ꢁꢁꢁ),
133.35 (C-1, 1ꢁ), 127.92 (C-2, 2ꢁ, 6, 6ꢁ), 114.44 (C-3,
3ꢁ, 5, 5ꢁ), 67.13 (C-2ꢁꢁ, 2ꢁꢁꢁ), 82.05 (C-1ꢁꢁꢁꢁꢁ, 2ꢁꢁꢁꢁ), 55.51
(OCH2), 22.34 (NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 21.65 (COCH3–
3ꢁꢁ, 3ꢁꢁꢁ); MS(ESI): m/z (M+Na)+ = 631; Anal. Calc.
for C28H28N6O6S2: C, 55.26%; H, 8.33%; N, 13.81%;
S, 10.52%; Found C, 55.28%; H, 8.35%; N, 13.79%; S,
10.54%.
2.26 Synthesis of N,Nꢁ-[5,5ꢁ-{4,4ꢁ-(but-2-ene-1,4-
diylbis(oxy))bis(4,1-phenylene)]bis(4-acetyl-4,5-
dihydro-1,3,4-thiadiazole-5,2-diyl)]diacetamide 4baꢁ
2.28 Synthesis of N,Nꢁ-[5,5ꢁ-{4,4ꢁ-(1,2-phenylenebis
(methylene)}bis(oxy)bis(4,1-phenylene)]bis(4-acetyl-4,
5-dihydro-1,3,4-thiadiazole-5,2-diyl)]diacetamide 4bcꢁ
The compound 4baꢁ was obtained by refluxing bis-
thiosemicarbazone 3baꢁ (1.0 g, 0.0024 mol) with acetic
anhydride (30 ml) under the similar conditions as de-
scribed above for 4aaꢁ.
The compound 4bcꢁ was synthesized by refluxing
bisthiosemicarbazone 3bcꢁ (1.0 g, 0.0020 mol) with
acetic anhydride (30 ml) under the similar conditions as
described above for 4aaꢁ.
4baꢁ: Cream solid, Yield 70%; m.p.:154–156◦C. IR
(KBr) cm−1 3067 (NH), 2955, 2903 (methylene C-H),
1695, 1637 (C=O), 1609 (C=N), 1239, 1080 (C-O);
1H-NMR (DMSO-d6): δ 11.45 (2H, s, NHCOCH3–5ꢁꢁ,
5ꢁꢁꢁ), 7.68 (2H, s, H-2ꢁꢁ, 2ꢁꢁꢁ), 7.22 (2H, d, Jo = 8.2 Hz,
H-2, 2ꢁ, 6, 6ꢁ), 6.85 (2H, d, Jo = 8.5 Hz, H-3, 3ꢁ, 5, 5ꢁ),
6.72 (2H, brs, OCH2CH=), 4.56 (4H, s, OCH2CH=),
2.16 (6H, s, COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 2.11 (6H, s, NHCOCH3–
5ꢁꢁ, 5ꢁꢁꢁ); 13C-NMR (DMSO-d6): δ 169.02 (5ꢁꢁ, 5ꢁꢁꢁ-
NHCOCH3), 167.18 (COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 157.89 (C-4, 4ꢁ),
146.06 (C-5ꢁꢁ, 5ꢁꢁꢁ), 133.35 (C-1, 1ꢁ), 127.92 (C-2, 2ꢁ, 6,
6ꢁ), 126.62 (OCH2CH=), 114.44 (C-3, 3ꢁ, 5, 5ꢁ), 67.13
(C-2ꢁꢁ, 2ꢁꢁꢁ), 65.64 (OCH2CH=), 22.44 (NHCOCH3–5ꢁꢁ,
5ꢁꢁꢁ), 21.85 (COCH3–3ꢁꢁ, 3ꢁꢁꢁ); MS(ESI): m/z (M+1)+ =
611; Anal. Calc. for C28H30O6N6S2: Calc. C, 55.08%;
H, 4.91%, N, 13.77%; S, 10.49%; Found C, 55.00%; H,
4.97%, N, 13.70%; S, 10.55%.
4bcꢁ: Off white solid, Yield 52%; m.p.: 198–200◦C.
IR (KBr) cm−1 3065 (NH), 2950, 2935 (methylene
C-H), 1683, 1632 (C=O), 1607 (C=N), 1240, 1033 (C-
O); 1H-NMR (DMSO-d6): δ 11.51 (2H, s, NHCOCH3–
5ꢁꢁ, 5ꢁꢁꢁ), 7.42 (2H, td, J = 3.2, 5.1 Hz, H-4ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ),
7.28 (2H, td, J = 3.3, 5.4 Hz, H-3ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 7.13 (4H, d,
Jo = 8.5 Hz, 2, 2ꢁ, 6, 6ꢁ), 6.85 (4H, d, Jo = 8.6 Hz, H-
3, 3ꢁ, 5, 5ꢁ), 6.65 (2H, s, H-2ꢁꢁ, 2ꢁꢁꢁ), 5.11 (4H, s, OCH2),
2.16 (6H, s, COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 2.01 (6H, s, NHCOCH3–
5ꢁꢁ, 5ꢁꢁꢁ); 13C-NMR (DMSO-d6): δ 169.04 (NHCOCH3–
5ꢁꢁ, 5ꢁꢁꢁ), 167.26 (COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 157.96 (C-4, 4ꢁ),
146.09 (C-5ꢁꢁ, 5ꢁꢁꢁ), 134.70 (C-1ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁ), 133.48 (C-1, 1ꢁ),
127.48 (C-2, 2ꢁ, 6, 6ꢁ), 128.40 (C-3ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ), 126.66 (C-
4ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ), 114.56 (C-3, 3ꢁ, 5, 5ꢁ), 67.26 (C-2ꢁꢁ, 2ꢁꢁꢁ), 65.68
(OCH2), 22.43 (NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 21.85 (COCH3–
3ꢁꢁ, 3ꢁꢁꢁ); MS(ESI): m/z (M+Na)+ = 683; Anal. Calc.

Synthesis of bisthiadiazolines
711
for C32H32O6N6S2: Calc. C, 58.18%; H, 4.85%, N, 158.12 (C-4, 4ꢁ), 146.14 (C-5ꢁꢁ, 5ꢁꢁꢁ), 135.70 (C-1, 1ꢁ),
12.73; S, 9.69%; Found C, 58.12%; H, 4.80%, N, 12.78; 133.22 (C-4ꢁꢁꢁꢁ, 4ꢁꢁꢁꢁꢁ), 128.11 (C-1ꢁꢁꢁꢁ, 1ꢁꢁꢁꢁꢁ), 127.79 (C-
S, 9.73%.
2, 2ꢁ, 6, 6ꢁ), 126.73 (C-3ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁꢁ), 126.63 (C-
2ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁꢁ), 114.51 (C-3, 3ꢁ, 5, 5ꢁ), 69.04 (C-2ꢁꢁ,
2ꢁꢁꢁ), 65.75 (OCH2), 22.41 (NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 21.83
(COCH3–3ꢁꢁ, 3ꢁꢁꢁ); MS(ESI): m/z (M+Na)+ = 759;
Anal. Calc. for C38H36O6N6S2: Calc. C, 61.96%; H,
4.89%; N, 11.41%; S, 8.69%; Found C, 61.90%; H,
4.83%, N, 11.36%; S, 8.62%.
2.29 Synthesis of N,Nꢁ-[5,5ꢁ-{4,4ꢁ-(1,4-phenylenebis
(methylene)}bis(oxy)bis(4,1-phenylene)]bis(4-acetyl-4,
5-dihydro-1,3,4-thiadiazole-5,2-diyl)]diacetamide 4bdꢁ
The compound 4bdꢁ was prepared by refluxing bisthio-
semicarbazone 3bdꢁ (1.0 g, 0.0020 mol) with acetic an-
hydride (30 ml) under the similar conditions as described
above for 4aaꢁ.
3. Results and discussion
3.1 Chemistry
4bdꢁ: Cream solid, Yield 58%; m.p.: 142–144◦C. IR
The bis(1,3,4-thiadiazolines) 4a(aꢁ-eꢁ) and 4b(aꢁ-eꢁ) re-
quired for this study were prepared starting from
the 2/4-hydroxybenzaldehyde which was reacted with
suitable alkylating agent (trans-1,4-dibromo-2-butene,
1,4-dichloro-2-butyne, α,αꢁ-dibromo-o-xylene, α,αꢁ-
dibromo-p-xylene and 4,4ꢁ-bischloromethyl-diphenyl)
in the presence of anhydrous K2CO3/dry acetone and
Bu4N+I− (PTC) to obtain bisaldehydes 2a(aꢁ-e) and
2b(aꢁ-eꢁ), respectively. The bisaldehydes were reacted
with thiosemicarbazide in the presence of dry EtOH
under refluxing condition to yield bis-thiosemicarba-
zones 3a(aꢁ-eꢁ) and 3b(aꢁ-eꢁ) which were further refluxed
under acetic anhydride medium21–24 to yield the final
products 4a(aꢁ-eꢁ) and 4b(aꢁ-eꢁ) (scheme 1).
(KBr) cm−1 3064 (NH), 2930 (methylene C-H), 1683
1
(C=O), 1608 (C=N), 1240, 1010 (C-O); H-NMR
(DMSO-d6): δ 11.37 (2H, s, NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 7.60
(2H, s, H-2ꢁꢁ, 2ꢁꢁꢁ), 7.34 (4H, s, H-2ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ),
7.14 (4H, d, Jo = 8.2 Hz, H-2, 2ꢁ, 6, 6ꢁ), 6.83 (4H,
d, Jo = 8.2 Hz, H-3, 3ꢁ, 5, 5ꢁ), 4.95 (4H, s, OCH2),
2.19 (6H, s, COCH3–3ꢁꢁ, 3ꢁꢁꢁ), 2.11 (6H, s, NHCOCH3–
5ꢁꢁ, 5ꢁꢁꢁ); 13C-NMR (DMSO-d6): δ 169.04 (NHCOCH3–
5ꢁꢁ, 5ꢁꢁꢁ), 167.36 (COCH3–3ꢁ, 3ꢁꢁꢁ), 158.04 (C-4, 4ꢁ),
14ꢁ 6.15 (C-5ꢁꢁ, 5ꢁꢁꢁ), 134.70 (C-1ꢁꢁꢁꢁ, 4ꢁꢁꢁꢁ), 133.02 (C-1,
1 ), 127.27 (C-2, 2ꢁ, 6, 6ꢁ), 126.67 (C-2ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ,
6ꢁꢁꢁꢁ), 114.48 (C-3, 3ꢁ, 5, 5ꢁ), 69.04 (C-2ꢁꢁ, 2ꢁꢁꢁ), 65.74
(OCH2), 22.40 (NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 21.82 (COCH3–
3ꢁꢁ, 3ꢁꢁꢁ); MS(ESI): m/z (M+1)+ = 661; Anal. Calc. for
C32H32O6N6S2: Calc. C, 58.18%; H, 4.85%, N, 12.73;
S, 9.69%; Found C, 58.23%; H, 4.80%, N, 12.78; S,
9.63%.
The structures of compounds 2a(aꢁ-eꢁ), 2b(aꢁ-eꢁ),
3a(aꢁ-eꢁ), 3b(aꢁ-eꢁ), 4a(aꢁ-eꢁ) and 4b(aꢁ-eꢁ) were deter-
mined from the analysis of their spectroscopic data
1
(IR, H and 13C-NMR and ESI-Mass) and elemental
analysis.
2.30 Synthesis of N,Nꢁ-[5,5ꢁ-{4,4ꢁ-(biphenyl-4,4ꢁ-diylbis
(methylene)}bis(oxy)bis(4,1-phenylene)]bis(4-acetyl-4,
5-dihydro-1,3,4-thiadiazole-5,2-diyl)]diacetamide 4beꢁ
The IR spectra of 2a(aꢁ-eꢁ) and 2b(aꢁ-eꢁ) exhibited
the carbonyl group absorptions at 1688–1675 cm−1 and
1691–1678 cm−1, respectively. In their H-NMR spec-
1
tra, signal corresponding to CHO group appeared at
δ 10.61–10.43 and 9.88–9.78 as sharp singlet and the
aromatic ring protons (H-2,2ꢁ,3,3ꢁ,5,5ꢁ,6,6ꢁ) were cen-
tred at δ 7.90–7.02 and 7.82–6.99 as suitable signals
(see experimental). 13C-NMR spectra revealed the most
downfield signal at δ 190–188 (C=O) and 191–190
(C=O) and the resonances belonging to the aromatic
ring were suitably placed at δ 161–112 and 164–114,
respectively (see experimental).
The compound 4beꢁ was synthesized by refluxing
bisthiosemicarbazone 3beꢁ (1.0 g, 0.0017 mol) with
acetic anhydride (30 ml) under the similar conditions as
described above for 4aaꢁ:
4beꢁ: Off white solid, Yield 63%; m.p.: 158–162◦C.
IR (KBr) cm−1 3065 (NH), 2943, 2903 (methylene C-
H), 1693, 1636 (C=O), 1608 (C=N), 1241, 1036 (C-
O); 1H-NMR (DMSO-d6): δ 11.54 (2H, s, NHCOCH3–
5ꢁꢁ, 5ꢁꢁꢁ), 7.56 (4H, d, Jo = 8.1 Hz, H-3ꢁꢁꢁꢁ, 3ꢁꢁꢁꢁꢁ, 5ꢁꢁꢁꢁ,
5ꢁꢁꢁꢁꢁ), 7.44 (4H, d, Jo = 8.0 Hz, H-2ꢁꢁꢁꢁ, 2ꢁꢁꢁꢁꢁ, 6ꢁꢁꢁꢁ, 6ꢁꢁꢁꢁꢁ),
7.15 (4H, d, Jo = 8.4 Hz, H-2, 2ꢁ, 6, 6ꢁ), 6.88 (4H, d,
Jo = 8.4 Hz, H-3, 3ꢁ, 5, 5ꢁ), 6.65 (2H, s, H-2ꢁꢁ, 2ꢁꢁꢁ),
5.04 (4H, s, OCH2), 2.16 (6H, s, COCH3- 3ꢁꢁ, 3ꢁꢁꢁ), 2.02
(6H, s, NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ); 13C-NMR (DMSO-d6): δ
169.04 (NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ), 167.35 (COCH3–3ꢁꢁ, 3ꢁꢁꢁ),
The IR spectra of 3a(aꢁ-eꢁ) and 3b(aꢁ-eꢁ) also exhib-
ited the NH stretching at 3360–3145 cm−1 and did not
reveal any absorption in the carbonyl group region
which describes the transformation of C=O group dur-
1
ing the reaction. The significant feature of their H-
NMR spectra was the appearance of sharp singlet at
δ 8.60–8.52 and 8.06–7.93 which could be very well
ascribed to azomethyne proton (H-1ꢁꢁ and H-1ꢁꢁꢁ) and the

712
Mohamad Yusuf et al.
OH
OHC
1a and 1b
CH Br
BrCH
x
/ dry acetone
2
2
anhyd
K2CO3/ PTC /
3
3'
4
4'
2
1
2'
1'
OCH2
X
CH O
2
5'
5
CHO
OHC
6
6'
2a(a'-e') and 2b(a'-e')
dry EtOH / HCl
H N C NH NH
2
/
2
S
3'
3
2'
4'
CH O
4
OCH
2
’
X
2
H
H
2
H
1"'
3"'
NH
1
2"'
4"' 5"'
N
2"
5"
N
4"
S
3"
1"
5'
1'
5
N
NH
N
6'
6
H
H
H
S
’
3a(a'-e') and 3b(a'-e')
Ac O
/
2
3'
3
6
O
CH3
H C
3
O
4
5
4'
2'
2
X
OCH2
CH2O
N3""
1
1'
3" N
2"'
2"
5'
N4"'
5"'
4"
N
5"
6'
H
H
S1"
S1"'
H3C
NH
NH
CH3
O
4a(a'-e') and 4b(a'-e')
O
a: 2-OCH2XCH2O-2' , b: 4-OCH2XCH2O-4'
1"" 2""
3""
2""
1""
1"" 2""
4""
3""
a': X =
, c': X = 6""
CH=CH
, b': X =
, d ' : X =
4""
5""
6""
5""
3""'
3""
2""'
1""'
2""
1""
; PTC = Bu4N + I-
4""'
e': X =
4""
5""'
5""
6""'
Scheme 1. N,Nꢁ-[5,5ꢁ-{2,2ꢁ-(bis-alkoxy)bis(2,1-phenylene)]bis(4-acetyl-4,
5-dihydro-1,3,4-thiadiazole-5,2-diyl)]diacetamides 4a(aꢁ-eꢁ) and 4b(aꢁ-eꢁ).
four doublets in the aromatic region at δ 8.08–6.90 inte- 11.32–11.26, respectively and these hydrogens were
grating for four hydrogens each could be denoted by also exchangeable with D2O. In the 13C-NMR spectra
H-3,3ꢁ,4,4ꢁ,5,5ꢁ,6,6ꢁ and the doublets in the range of δ of 3a(aꢁ-eꢁ) and 3b(aꢁ-eꢁ), C-4ꢁꢁ, 4ꢁꢁꢁ and C-1ꢁꢁ, 1ꢁꢁꢁ were
7.66–7.55 and 6.97–6.85 were assignable to H-2,2ꢁ,6,6ꢁ found placed at δ 178–177 and 143–138, respectively
and H-3,3ꢁ,5,5ꢁ, respectively. 5ꢁꢁ,5ꢁꢁꢁ-NH2 and 3ꢁꢁ,3ꢁꢁꢁ-NH and the resonances present at δ 159–156 and 159–158
protons appeared as two broad singlets at δ 8.18–7.47 and 129–125 and 128–126 may be furnished by the
and 8.01–7.29 and sharp singlet at δ 11.50–11.40 and aromatic carbons C-2, 2ꢁ and C-6, 6ꢁ, respectively.

Synthesis of bisthiadiazolines
713
60
50
40
30
20
10
0
E. coli
B. subtilis
K. pneumoniae
S. aureus
P. aeruginosa
A. janus
P. glabrum
3aa' 3ab'
3ad' 3ae' 4aa' 4ab'
4ad' 4ae'
4ac'
3ac'
Amoxycillin
Fluconazle
Compounds
Figure 1. In vitro MIC (μg/mL) of compounds 3aaꢁ-3aeꢁ and 4aaꢁ-4aeꢁ.
60
50
40
30
20
10
0
E. coli
B. subtilis
K.
pneumoniae
S.
aureus
P.
aeruginosa
A.
janus
3ba' 3bb'
3bd' 3be' 4ba' 4bb'
4bd' 4be'
Amoxycillin
Fluconazole
3bc'
4bc'
P.
glabrum
Name of Compounds
Figure 2. In vitro MIC (μg/mL) for compounds 3baꢁ-3beꢁ and 4baꢁ-4beꢁ.
30
K. pneumoniae.
25
20
15
10
5
P.aerugenosa.
E. coli
S. aureus
B. subtilis
A. janus
P. glabrum
0
3aa' 3ab'
3ad' 3ae' 4aa' 4ab'
4ad' 4ae'
4ac'
3ac'
Amoxycillin
Fluconazole
Name of Compounds
Figure 3. In vitro zone of inhibition (mm) of compounds 3aaꢁ-3aeꢁ and 4aaꢁ-4aeꢁ.
30
K. pneumoniae
25
20
15
10
5
P. aerugenosa
E. coli
S. aureus
B. subtilis
0
3ba' 3bb'
3bd' 3be' 4ba' 4bb'
4bd' 4be'
4bc'
3bc'
Amoxycillin
A. janus
Fluconazole
P. glabrum
Compounds
Figure 4. In vitro zone of inhibition (mm) of compounds 3baꢁ-3beꢁ and 4baꢁ-4beꢁ.

714
Mohamad Yusuf et al.
Table 1. MIC (μg/mL)of compounds 3aaꢁ-3aeꢁ and 4aaꢁ-4aeꢁ.
Gram-negative bacteria
Gram-positive bacteria
Fungi
Aspergillus
Compound
no.
Klubsellia
Pseudomonas
aeruginosa
Escherichia
coli
Staphylococcus
aureus
Bacillius
subtilis
Pencilluim
glabrum
pneumoniae
janus
3aaꢁ
12.5
6.25
12.5
25
12.5
12.5
6.25
12.5
12.5
50
12.5
12.5
6.25
6.25
12.5
12.5
12.5
6.25
25
25
25
12.5
12.5
25
6.25
12.5
25
12.5
25
12.5
6.25
6.25
12.5
25
25
25
25
12.5
12.5
6.25
12.5
6.25
12.5
25
6.25
6.25
25
3abꢁ
6.25
12.5
12.5
12.5
12.5
12.5
6.25
6.25
12.5
–
3acꢁ
12.5
12.5
12.5
3.12
12.5
25
12.5
25
3.12
–
3adꢁ
3aeꢁ
4aaꢁ
25
4abꢁ
12.5
12.5
25
25
3.12
–
4acꢁ
4adꢁ
4aeꢁ
25
3.12
–
Amoxicillin
Fluconazole
3.12
–
3.12
–
–
3.12
3.12
IR spectra of bisthiadiazolines 4a(aꢁ-eꢁ) and 4b(aꢁ- δ 22–20 in their 13C-NMR spectra. The presence of
eꢁ) displayed major absorptions at 3066–3062, 1689– two carbonyl groups in 4a(aꢁ-eꢁ) and 4b(aꢁ-eꢁ) was con-
1632 and 1604–1601 cm−1 which could be ascribed firmed by the availability of two resonances at δ 170–
to NH, C=O and C=N stretchings, respectively. 168 and 169–167 and the signals resonating at δ 154–
1H-NMR (400 MHz, DMSO) spectra of these com- 153 and 158–157 could be allotted to C-2, 2ꢁ and C-
pounds had D2O exchangeable singlet at δ 11.54– 4, 4ꢁ, respectively. The C=N (5ꢁꢁ, 5ꢁꢁꢁ) moiety of the thia-
11.43 and 11.51–11.31 which may be represented diazoline ring resulted suitable signals at δ 148–146 and
by NHCOCH3–5ꢁꢁ, 5ꢁꢁꢁ protons. The thiadiazoline ring 147–146 in 4a(aꢁ-eꢁ) and 4b(aꢁ-eꢁ), respectively.
hydrogen (H-2ꢁꢁ, 2ꢁꢁꢁ) produced singlet at δ 7.68–6.65
and the downfield resonance of this hydrogen could
be ascribed to its benzylic nature and its placement
between two heteroatoms (N and S). The signals
present at δ 2.28–2.12 (s) and 2.11–2.02 (s) could be
very well given by COCH3–3ꢁꢁ, 3ꢁꢁꢁ and NHCOCH3–
5ꢁꢁ, 5ꢁꢁꢁ methyl groups, respectively and these groups
have also been confirmed by the two resonances at
3.2 Antimicrobial activity
The antimicrobial activity of synthesized compounds was
screened in vitro by disc diffusion method25 against se-
lected pathogens which include Staphylococcous aureus,
Bacillius subtilis, Escherichia coli, Pseudomonas
glabrum and Klubsellia pneumoniae and fungus strains
Table 2. MIC (μg/mL) of compounds 3baꢁ-3beꢁ and 4baꢁ-4beꢁ.
Gram-negative bacteria
Gram-positive bacteria
Fungi
Aspergillus
Compound
no.
Klubsellia
Pseudomonas
aeruginosa
Escherichia
coli
Staphylococcus
aureus
Bacillius
subtilis
Pencilluim
glabrum
pneumoniae
janus
3baꢁ
6.25
6.25
12.5
25
12.5
12.5
6.25
12.5
12.5
6.25
6.25
6.25
6.25
6.25
3.12
–
6.25
12.5
25
12.5
25
6.25
6.25
25
6.25
25
12.5
12.5
6.25
6.25
6.25
3.12
–
12.5
25
6.25
25
12.5
12.5
12.5
25
12.5
50
12.5
25
3bbꢁ
3bcꢁ
12.5
12.5
12.5
12.5
12.5
12.5
12.5
12.5
3.12
–
12.5
12.5
12.5
6.25
6.25
12.5
12.5
12.5
–
3bdꢁ
25
3beꢁ
25
12.5
12.5
12.5
25
12.5
25
4baꢁ
12.5
12.5
25
12.5
25
3.12
–
4bbꢁ
4bcꢁ
4bdꢁ
4beꢁ
Amoxicillin
Fluconazole
3.12
–
–
3.12
3.12

Synthesis of bisthiadiazolines
715
were Aspergillus janus and Pencilluim glabrum. The
bacterial pathogens were subcultured on Muller–
Hinton Agar medium whereas fungus pathogens were
sub-cultured at malt extract. The newly prepared com-
pounds were screened for their antibacterial and anti-
fungal activity using paper disc method in vitro against
the above said strains at conc. 100 μg/ml. Amoxicillin
was used as reference drug for comparison. All the
compounds were also screened for MIC (tables 1 and
2) by using serial tube dilution method26 at concentra-
tion, 3.12, 6.25, 12.5, 25, 50 and 100 μg/mL against
the above said microorganisms and observed minimum
inhibitory concentration (MIC-μg/ml) values are given
in figures 1 and 2. The compounds 3abꢁ, 3baꢁ, 3bbꢁ,
4aaꢁ, 4abꢁ, 4acꢁ, 4adꢁ, 4baꢁ, 4bbꢁ, 4bcꢁ, 4bdꢁ and 4beꢁ
showed significant MIC (12.50–6.25 μg/ml) against the
tested microorganisms. In the disc diffusion method,
a standard 5 mm diameter sterilized filter paper disc
impregnated with the compound was placed on an agar
plate seeded with the test organism. The plates were
incubated for 24 h at 37◦C for bacteria and 48 h at
28◦C for fungi. The zones of inhibition of bacteria and
2. Er M, Unver Y, Sancak K, Degirmencioglu I and
Karaoglu SA 2009 Arkivoc 2 149
3. (a) Kornis G 1984 Comprehensive heterocyclic chem-
istry I (eds) A R Katritzky and C W Rees, Oxford:
Pergamon 4 545; (b) Kornis G I 1996 Comprehen-
sive heterocyclic chemistry II (ed) R C Storr, Oxford:
Pergamon 4 379
4. Chapleo C B, Myers P L, Smith A C B, Stillings M R,
Tulloch I F and Walter D C 1988 J. Med. Chem. 31 7
5. Chapleo C B, Myers M, Myers P L, Saville J F, Smith A
C B, Stilling M R, Tulloch I F, Walter D S and Welbourn,
A D 1986 J. Med. Chem. 29 2273
6. Turner S, Myers M, Gadie B, Nelson A J, Pape R, Saville
J F, Doxey J C and Berridge T L 1988 J. Med. Chem. 31
902
7. Mazzone G, Pignatello R, Mazzone S, Panico A, Penisi
G, Castana R and Mazzone P 1993 Farmaco 48 1207
8. Shukla H K, Desai N C, Astik R R and Thaker K A 1984
J. Indian Chem. Soc. 61 168
9. Desai N C, Shukla, H K, Parekh B P and Thaker K A
1984 J. Indian Chem. Soc. 61 455
10. Umamatheswari S and Kabilan S 2009 J. Mol. Struct.
938 142
11. Mobio I G, Soldatenkov A T, Federov V O, Ageev E A,
Sergeeva N D, Lin, S, Stashenku E E, Prostakov N S and
Andreeva E L 1989 Khim. Farm. Zh. 23 421
fungi growth around the disc were observed. DMSO 12. Katritzky A R and Fan W J 1990 J. Org. Chem. 55
3205
was used as a control and it did not show any activity
13. Ganellin C R and Spickett R G W 1965 J. Med. Chem. 8
619
of inhibition (mm) has been recorded as the average
14. Desai K and Baxi A J 1992 Indian J. Pharm. Sci. 54
against the strains of micro-organisms used. The zone
diameters which are given in figures 3 and 4.
183
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17. Abbas A A and Rateb N M 2005 Phosphorus, Sulfur
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4. Conclusion
It may be concluded that this study describes the gene-
ral method for the synthesis of new rigid chain linked 18. Mamun H M, Foysal M A, Mahabub M and Al-Amin
2010 J. Sci. Res. 2(2) 322
19. Abdelhamid A O, Ismail Z and Abdel-Aziem A 2008
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20. Mithun A and Holla B S 2007 Phosphorus, Sulfur
Silicon 182 981
new bisthiadiazolines under the normal conditions. The
nature of the internal spacer did not have any significant
effect on the formation and antimicrobial behaviour of
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Acknowledgement
Authors are thankful to the Council of Scientific and
Industrial Research (CSIR), New Delhi for providing
the financial support.
24. Hui X P, Chu C H, Zang Z Y, Wang Q and Zhang Q 2002
Indian J. Chem. 41B 2176
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