New 1,3,4-bisthiadiazolines: Synthesis, characterization and antimicrobial evaluations

Article abstract of DOI:10.1016/j.saa.2012.06.030

The bisthiadiazolines 4a-4g have been synthesized in good yields from the cyclization reactions of bisthiosemicarbazones 3a-3g with acetic anhydride. The condensation reaction of dibenzaldehydes 2a-2g with thiosemicarbazide in alcoholic medium provided 3a

Full text of DOI:10.1016/j.saa.2012.06.030

Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 97 (2012) 470–478
Contents lists available at SciVerse ScienceDirect
Spectrochimica Acta Part A: Molecular and
Biomolecular Spectroscopy
journal homepage: www.elsevier.com/locate/saa
New 1,3,4-bisthiadiazolines: Synthesis, characterization
and antimicrobial evaluations
⇑
Mohamad Yusuf , Manvinder Kaur, Payal Jain, Indu Solanki
Department of Chemistry, Punjabi University, Patiala 147002, Punjab, India
g r a p h i c a l a b s t r a c t
h i g h l i g h t s
New bisthiadiazolines built around the aliphatic chains of varying length has been synthesized. The struc-
tures of the intermediates and final bisheterocyclics were determined from the rigorous analysis of their
various spectroscopic data. The compounds 3f, 3g, 4f & 4g exhibited significant activity against the tested
microorganisms.
"
The aliphatic chains linked new
bisthiadiazolines have been
synthesized.
These compounds have been
prepared from the cyclization
reactions of the
"
bisthiosemicarbazones with acetic
anhydride.
O
CH2 (CH2)n CH2
O
O
H
N
O
H
N
S
S
"
"
All the products have been
characterized by using various
spectroscopic techniques.
The antimicrobial activities of these
compounds have also been studied.
CH3
H3C
H
O
H
H3C
N
N
N
N
CH3
O
4a-4g
n = 0, 2, 3, 4, 6, 8, 10
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 11 May 2012
Received in revised form 14 June 2012
Accepted 23 June 2012
Available online 30 June 2012
The bisthiadiazolines 4a–4g have been synthesized in good yields from the cyclization reactions of
bisthiosemicarbazones 3a–3g with acetic anhydride. The condensation reaction of dibenzaldehydes
2a–2g with thiosemicarbazide in alcoholic medium provided 3a–3g and former were obtained from
the O-alkylation of 3-hydroxybenzaldehyde with suitable 1,x-dibromoalkanes under alkaline conditions
in the presence of dry EtOH/DMF. The intermediates 3a–3g and bishetrocyclics 4a–4g were also screened
for their in vitro antimicrobial activities against seven bacterial strains (Klubsellia pneumoniae, Pseudomo-
nas aeruginosa, Escherichia coli, Straphylococcus aureus, Bacillius subtilis, Pseudomonas fluorescens and Strep-
toccus pyrogens) and five fungi strains (Aspergillius janus, Pencillium glabrum, Fusarium oxysporum,
Aspergillus sclerotiorum, Aspergillus niger). The compounds 3f, 3g, 4f & 4g were found to be significantly
active against the tested microorganisms.
Keywords:
Bisthiosemicarbazones
Dibenzaldehydes
Bisthiadiazolines
Antimicrobial activity
MIC
Ó 2012 Elsevier B.V. All rights reserved.
Cyclization reactions
1. Introduction
considerable attention in the past decades because these com-
pounds constitute the structural frameworks of several naturally
Thiadiazolines are the heterocyclic compounds containing three
heteroatoms in the five membered ring and these products are of
major interest due to their immense biological activities [1]. The
syntheses of substituted thiadiazolines [2–4] have attracted the
occurring alkanoids that show a wide range of pharmacological be-
haviors [5]. These derivatives exhibit antifungal [6], anti-inflam-
matory [7], anticonvulsant [8], antiviral [9], plant growth
regulatory [10], hypertensive, central nervous system depressant
[11], anticancer [12] and carbonic anhydrase inhibitory [13] activ-
ities. By keeping these aspects in view and in continuation of our
studies [14a,b] on the bisheterocyclic compounds, present re-
⇑
Corresponding author.
E-mail address: yusuf_sah04@yahoo.co.in (M. Yusuf).
1386-1425/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.saa.2012.06.030

M. Yusuf et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 97 (2012) 470–478
471
searches have been focused on the synthesis of new bisthiadiazo-
lines 4a–4g built around the alkyl chain of varying lengths. The
major impetus behind these investigations was to study the effect
of the internal spacer length upon the formation and antimicrobial
behavior of the final bisheterocyclic compounds.
2759–2717 cmꢀ1 due to aldehyde C–H stretching. In the 1H NMR
spectra (400 MHz, DMSO-d6) of dibenzaldehydes, the signal placed
at d 9.98–9.89 could be ascribed to CHO proton. The hydrogens
(H-2, 6, 5 & 4) of the phenyl ring were found to be placed at d
7.86–7.37 (2H, s), 7.49–7.36 (2H, m), 7.46–7.30 (2H, d, Jo = 6.6 Hz)
and 7.27–7.09 (2H, m) respectively. The resonances of internal
chain OCH2 group were placed in the aliphatic region at d 4.45–
3.93. The UV–Vis spectra of 2a & 2d–2g had two absorption bands
at 340–318 and 275–258 nm which could be ascribed to n ? p⁄
2. Results and discussion
The bisthiadiazolines 4a–4g required for the present study were
obtained starting from 3-hydroxybenzaldehyde 1 which was re-
and
p ?
p⁄ transitions respectively.
13C NMR (100 MHz, DMSO-d6) spectra of dibenzaldehydes (2a &
2d–2g) proved instrumental to corroborate their proposed
structures. The presence of aldehyde group was confirmed by
appearance of signal at d 192.37–192.12 (C@O). The aromatic car-
bon atoms showed suitable signals at d 159.72–159.13 (C-3),
137.80–137.51 (C-1), 130.08–129.98 (C-6), 123.56–122.20 (C-5),
122.00–121.16 (C-4) & 113.35–112.59 (C-2); the downfield reso-
nance of C-3 as compared to other carbon atoms can be ascribed
to its direct linkage to the electronegative oxygen atom. The reso-
nance placed at d 68.30–67.60 could be generated by internal chain
OCH2 group.
acted [15] with suitable 1,x-dibromoalkanes under refluxing
conditions in the presence of dry EtOH/KOH/DMF to yield diben-
zaldehydes 2a–2g. The later were treated with thiosemicarbazide
in dry EtOH and catalytic amount of HCl to furnish bisthiosemicar-
bazones 3a–3g which were further refluxed in Ac2O to furnish bis-
thiadiazolines 4a–4g in good yields (Scheme 1).
The structures of the prepared compounds (2a, 2d–2g, 3a–3g &
4a–4g) were based upon their spectroscopic data (IR, 1H NMR, 13C
NMR & ESI-MS) and elemental analysis results also confirmed the
purity of these products.
IR spectra of dibenzaldehydes (2a & 2d–2g) showed strong
absorption bands at 1698–1679 cmꢀ1 due to conjugated C@O
group along with the two additional bands at 2874–2850 and
In the IR spectra of 3a–3g noticeable absorption bands were
present in the regions at 3398–3368, 3250–3238, 3159–3154
OH
CHO
1
+
-
Δ
K2CO3/dry acetone/ Bu4N I /Br-CH2-(CH2)n-CH2-Br/
5
1
4
2
6
O
CH2
(CH2)n
CH2
O
3
OHC
CHO
2a-2g
NH2NHCSNH2
dry EtO
H /HCl
/
Δ
4'
5'
H
O
CH2 (CH2)n
CH2
6'
O
S
4
α
1
2'
S
H
H
H
N
2
N
5
N
N
N
H
N
3
1'
H
β
3a-3g
H
H
Ac O
Δ
2
/
5'
4'
O
CH2 (CH2)n CH2
O
6'
O
H
O
3'
H
1
S
N
S
2'
1'
N
2'''
CH3
N
H3C
3'''
5
2
H
1'''
H
H3C
N
N
N
CH3
2''
1''
4
3
O
O
4a-4g
a b c d e f
g
n = 0, 2, 3, 4, 6, 8, 10
Scheme 1. Synthesis of aliphatic chain linked bisthiadiazolines 4a–4g.

472
M. Yusuf et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 97 (2012) 470–478
O
O
(CH
)
2
12
S
S
H
H
H
(M+1)
(M+Na)
m/z 579 (4%)
N
N
N
H
m/z 557 (9%)
N
N
H
N
H
H
H
-N2H2
-CH2O2
-CN2H3S
+
.
+
.
(CH
)
11
2
O
(CH
)
O
S
S
H
2
12
H
H
O
O
(CH
)
11
S
2
H
H
N
N
N
H
N
N
H
N
S
S
N+
N
N
H
N
H
H
H
N
N
H
N
H
N
H
H
m/z 481 (19%)
-C2H4
m/z 510 (35%)
-H+
H
H
H
H
m/z 512 (7%)
-H+
+
.
(CH
)
11
2
S
S
H
O
(CH
)
O
+
N
2
10
O
O
(CH
)
11
S
2
N
N
N
H
H
N
N
H
S
S
N+
H
N
H
N
N
H
H
H
N
N
H
N
H
N
H
H
H
m/z 509 (100%)
H
+
H
H
m/z 511 (11%)
m/z 453 (12%)
-NH
+
-C2H5N2S2
.
+
.
CH
3
+H+
S
O
O
O
(CH
)
O
m/z 179 (6%)
(CH
)
11
2
10
2
S
N
H
N
H
H
N
N
HN
N
N
+
m/z 390 (5%)
-C4H8
H
H
H
m/z 438 (22%)
-C2H6
m/z 178
-CH3NS
+
.
+
.
O
O
(CH
)
7
O
O
(CH
)
8
2
2
CH
S
3
N
N
N
N
N
m/z 334 (7%)
+
N
H
H
m/z 408 (13%)
-C6H11
m/z 117 (11%)
S
-C7H10N2O
-C10H10NO2
+
O
(CH2)
3
O
O
CH2
CH2
CH2
CH2
CH2
CH2
CH3
CH2
+
NH
N
N
H
m/z 149 (14%)
N
m/z 293 (10%)
-C2H2N3
m/z 159 (4%)
+
.
O
(CH2)
3
O
m/z 228 (11%)
-CH2
+
.
O
(CH2)
2
O
m/z 215 (8%)
Chart 1. Mass fragmentation pattern of 3g.
(N–H), 3027–3025 (aromatic C–H), 2937–2920, 2870–2849
spectra of 3a–3g. The downfield resonance present at d 158.92–
158.69 could be furnished by C-30 due to the direct linkage to this
carbon to the electronegative oxygen atom and the resonance ob-
served at d 142.62–142.34 was easily provided by C@N group. The
remaining signals in aromatic region were found to be placed at d
135.39–135.10 (C-10), 129.33–129.15 (C-60), 120.80–119.93 (C-50),
116.24–116.12 (C-40) & 111.57–111.33 (C-20). The OCH2 and
{(CH2)n} group belonging to the internal spacer unit furnished a
suitable resonance at d 67.44–66.98 and 28.98–23.76, respectively.
IR spectra of 4a–4g did not exhibit any absorption band in the
region at 1179–1177 cmꢀ1 indicating the involvement of C@S moi-
ety during the cyclization reaction of 3a–3g and here major bands
were observed in the region at 1698–1695, 1640–1638 (C@O) and
1607–1605 (C@N) cmꢀ1. The UV–Vis spectra of 4a–4g had two
maxima at 344–341 & 278–269 nm which may be ascribed by
(methylene C–H), 1600–1599 (C@N) and 1179–1177 (C@S) cmꢀ1
.
The resonance placed in 1H NMR spectra (400 MHz, DMSO-d6)
of 3a–3g at d 11.43–11.40 was assignable to 3-NH proton and
two broad singlets were found resonating at d 8.02–7.62 & 7.73–
7.42 due to NH-b & NH-a respectively. The azomethyne hydrogen
(H-1) was present at d 8.03–8.02 (2H) as a sharp singlet. The aro-
matic protons H-20, 60, H-50& H-40 provided suitable signals at d
7.32–7.25 (4H, t, Jo = 7.8 Hz), 7.21–7.18 (2H, d, Jo = 7.6 Hz) &
6.97–6.88 (2H, dd, Jm,o = 1.9, 7.9 Hz) respectively. The upfield reso-
nance of later could be due to the +I effect of C-30 alkoxy group. A
singlet integrating for four hydrogens at d 4.29–3.98 may be allot-
ted to OCH2 group and remaining (CH2)n groups were analyzed by
the signals of appropriate multiplicities at d 1.99–1.25. UV–Vis
spectra of 3a–3g had kmax at 362–318 nm which could be gener-
ated by n ? p⁄ transition.
n ? p⁄ and
p ?
p⁄ transitions, respectively.
The presence of C@S group was confirmed by the appearance of
A comparison of 1H NMR spectra (400 MHz, DMSO-d6) of 3a–3g
& 4a–4g shows that resonances present at d 8.02–7.62 & 7.73–7.42
a signal at d 177.98–177.92 in the 13C NMR (100 MHz, DMSO-d6)

M. Yusuf et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 97 (2012) 470–478
473
CH
O
CH
O
(CH )
2 10
2
2
O
O
(M+Na)
S
(M+1)
S
H C
NH
m/z 747 (28%)
3
m/z 725 (94%)
-C16H20O2N3S
NH
CH
3
H
H
N
N
H C
3
N
N
CH
3
-C4H6O2N
O
O
CH2 CH+2
CH2
CH2 CH2
CH2 CH2
CH2
O
CH
O
CH
O
(CH )
2 10
O
2
2
O
S
S
H C
NH
3
S
H C
NH
3
+
H
H
H
N
H
N
N
N
CH
3
N
N
CH
3
m/z 390 (7%)
-C2H4
O
m/z 624 (21%)
-C3H6
O
CH2 CH2
CH+2
CH2
CH2 CH2
O
CH
O
CH
O
O
(CH )
2 7
2
2
O
S
S
H C
NH
3
S
H C
3
NH
+
H
H
H
N
H
N
N
N
CH
3
N
N
CH
3
m/z 582 (10%)
-C3H4O
O
m/z 362 (4%)
O
-C2H4
CH+2
CH2
CH2 CH2
O
O
CH
O
CH
O
(CH )
2 6
2
2
O
S
H C
NH
3
S
S
H C
3
NH
H
+
H
N
N
H
CH
3
N
H
N
N
N
H
O
m/z 334 (3%)
-C6H11O2
m/z 526 (24%)
-C2H2O
CH
O
CH
O
(CH )
2 6
2
2
O
S
S
S
H N
2
H C
NH
3
+
H
H
H
N
H
N
N
N
H
N
N
H
m/z 484 (9%)
-NH3
m/z 221 (4%)
CH
O
CH
O
(CH )
2 6
2
2
S
S
+
N
N
N
N
m/z 467 (13%)
-C3H6O
CH
O
CH
(CH
)
3
2
2
2
S
S
+
N
N
N
N
m/z 409 (9%)
Chart 2. Mass fragmentation pattern of 4g.
due to NH-b & NH-
a
respectively in the former compounds were
146.19–146.09. The aromatic carbon atoms (C-10, 20, 30, 40, 50& 60)
were found to be resonating at the suitable positions (see experi-
mental). The noticeable resonances in the aliphatic region were
present at d 67.39–67.00 (OCH2), 65.91–65.77 (C-2), 22.38–21.81
(3000-CH3) and 21.78–20.48 (200-CH3).
The extensive ESI-MS fragmentation studies of the bisthiose-
micarbazones 3a–3g & bisthiadiazolines 4a–4g also proved helpful
to confirm their proposed structures (see experimental). The mass
fragmentation pattern of representative compounds 3g & 4g have
been depicted in Charts 1 and 2, respectively.
found missing altogether in the later which clearly describes the
involvement of these hydrogens in the chemical transformations.
The aromatic protons (H-60, 50, 40 & 20) in 4a–4g were centered at
d 7.25–7.17 (2H, t, Jo = 8.2 Hz), 6.89–6.77 (2H, brs), 6.86–6.73
(2H, d, J = 4.2 Hz) and 6.84–6.72 (2H, brs), respectively. The singlet
integrating for two hydrogens at d 6.74–6.67 could be assigned to
H-2 and two more singlets at d 2.25–2.20 & 2.13–2.03 were easily
furnished by 3000-CH3 & 200-CH3 groups, respectively. The protons
belonging to the spacer units also produced suitable signals of
the appropriate multiplicities in the aliphatic region (vide
experimental).
2.1. Antimicrobial activity
In the 13C NMR (100 MHz, DMSO-d6) spectra of 4a–4g, down-
field signals at d 169.13–169.00 and 167.38–167.29 were desig-
nated to 2000-C@O and 100-C@O groups respectively and C@N
moiety of thiadiazoline ring could result a suitable resonance at d
All the synthesized bisthiosemicarbazones 3a–3g and bisthi-
adiazoline 4a–4g were screened for their in vitro antimicrobial activ-
ities against seven bacterial strains namely Klubsellia pneumoniae

474
M. Yusuf et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 97 (2012) 470–478
Table 1
MIC (lg/ml) data of bisthiosemicarbazones 3a–3g.
Compound No. Gram (ꢀve) bacteria
Gram (+ve) bacteria
Fungi
E. coli K. pneumoniae P. aeruginosa P. fluorescens S. aureus B. subtilis S. pyrogens A. janus P. glabrum A. niger F. oxysporum A. sclerotiorum
3a
3b
3c
3d
3e
3f
3g
16
32
16
16
16
16
8
32
32
32
16
16
8
16
4
–
32
32
16
16
16
16
8
16
16
32
16
8
8
16
4
32
16
16
32
16
16
8
64
32
16
8
16
8
8
2
–
32
64
32
16
16
16
16
4
64
16
32
16
16
8
16
–
2
32
32
32
16
16
16
8
16
16
8
16
8
8
16
–
32
32
16
16
16
16
8
32
64
32
16
16
8
8
–
2
Amoxicillin
Fluconazole
4
4
2
–
2
–
2
–
–
–
–
–
2
Table 2
MIC ( g/ml) data of bisthiadiazolines 4a–4g.
l
Compound
No.
Gram (ꢀve) bacteria
Gram (+ve) bacteria
Fungi
E.coli K. pneumoniae P. aeruginosa P. fluorescens S. Aureus B. subtilis S. pyrogens A. janus P. glabrum A. niger F. oxysporum A. sclerotiorum
4a
4b
4c
4d
4e
4f
4g
32
32
32
16
16
8
32
32
16
32
16
16
8
32
32
32
16
16
8
16
4
–
16
16
32
16
8
8
16
4
32
16
32
64
16
16
8
32
64
32
16
16
32
16
2
32
16
64
32
16
16
16
4
32
32
32
8
8
16
8
32
32
16
8
16
16
16
–
32
32
16
16
8
8
8
–
2
32
16
64
16
8
8
16
–
16
32
32
16
16
8
8
–
2
8
4
Amoxicillin
Fluconazole
4
–
2
–
–
2
–
–
–
–
2
2
(MTCC 3384), Pseudomonas aeruginosa (MTCC 424), Escherichia coli
(MTCC 443), Staphylococcus aureus (MTCC 96), Bacillius subtilis
(MTCC 441), Pseudomonas fluorescens (MTCC103), Streptoccus pyro-
gens ( MTCC442) and five fungal strains Aspergillius janus (MTCC
2751), Pencillium glabrum (MTCC 4951), Fusarium oxysporum
(MTCC2480), Aspergillus sclerotiorum (MTCC1008), Aspergillus niger
(MTCC281), respectively. Amoxicillin and Fluconazole were used as
standard drugs against bacterial and fungi strains, respectively.
The minimum inhibitory concentrations of the newly prepared
compounds (3a–3g & 4a–4g) were determined by using Serial tube
dilution method [16] at the concentration of 128, 64, 32, 16, 8, 4, 2
3. Conclusion
It may be concluded that this study describes the general and
efficient method for the synthesis of alkyl chain linked bisthiadiaz-
olines. The length of internal spacer had significant effect upon the
antibacterial and antifungal behavior of the bisheterocyclic prod-
ucts. The bisthiadiazolines linked through the longer aliphatic
chains (made up of ten & twelve methylene groups) showed better
antimicrobial properties as compared to the shorter chain
derivatives.
and 1 lg/ml against above said microorganisms. The bacterial and
4. Experimental
fungi strains susceptibility to the studied compounds was deter-
mined by the appearance of turbidity after 24 h of incubation at
37 °C and 72 h of incubation at 28 °C, respectively. The observed
Melting points reported are uncorrected. IR spectra were
scanned in KBr pellets on a Perkin Elmer RXIFT Infrared spectro-
photometer. 1H 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 silica gel suspended
in MeOH–CHCl3 and iodine vapours were used as visualizing agent.
MIC values (lg/ml) of 3a–3g & 4a–4g are presented in Table 1 &
Table 2, respectively.
It is evident from Table 1 that the compounds 3c–3g show sig-
nificant activities against the most of bacterial and fungal strains at
(MIC-8
(MIC-8
l
l
g/ml). The compound 3g showed significant activity
g/ml) against the strains, E. coli, P. aeruginosa, S. aureus,
B. subtilis (bacterial strains) and P. glabrum, F. oxysporum, A. sclero-
tiorum (fungi strains) while 3f displayed activity of same order
against K. pneumoniae, P. fluorescens, B. subtilis, A. janus, A. niger
and A. sclerotiorum. Further 3c, 3d & 3e were also active (MIC-
8 lg/ml) against the A. niger, B. subtilis and against P. fluorescens,
A. niger, respectively.
Similarly, Table 2 describes that compounds 4d–4g mainly pro-
hibited the growth of the fungi strains. The bisthaidiazoline 4g was
found to be very active (MIC-8 lg/ml) against bacterial and fungi
strains E. coli, K. pneumoniae, S. aureus and A. janus, A. niger and A.
sclerotiorum, respectively. The compound 4f also seems to be active
against bacterial strainsE. coli, P. aeruginosa, P. fluorescens and fungi
strains A. niger, F. oxysporum, A. sclerotiorum, respectively. The bis-
4.1. Synthesis of 3,30-[ethane-1,2-diylbis (oxy)] dibenzaldehyde 2a
3-Hydroxybenzaldehyde 1 (1.22 g, 0.01 mol) and KOH (0.55 g,
0.01 mol) was dissolved in alcohol (100 ml) and then solvent was
removed under vacuum. The residue was dissolved in DMF
(25 ml) and 1,2-dibromoethane (0.94 g, 0.005 mol) was added
slowly. The reaction mixture was refluxed for 4 h, during which
KBr was separated out. The solvent was removed in vacuo and
the remaining material was poured into iced HCl to give a solid
substance which was filtered under suction and thoroughly
washed with water. The crude product thus obtained was crystal-
lized from MeOH to give pure compound 2a.
heterocyclics 4d & 4e could exhibit significant activity (MIC-8
ml) against A. janus, P. glabrum, P. fluorescens, F. oxysporum strains.
l
g/
2ª: Yield (1.8 g, 66%); brown solid; m.p. 88–90 °C; IR (KBr): tmax
cmꢀ1: 3066 (aromatic C–H), 2941 (methylene C–H), 2873, 2738

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475
(aldehyde C–H), 1685 (C@O); UV–Vis (MeOH): kmax (nm) 340, 272;
4.6. Synthesis of 3,30-[decane-1,10-diylbis (oxy)]dibenzaldehyde 2f
1H NMR (400 MHz, DMSO-d6): d 9.98 (2H, s, CHO), 7.86 (2H, s, H-2),
7.49 (2H, m, H-6), 7.46 (2H, d, Jo = 6.6 Hz, H-5), 7.27 (2H, m, H-4),
4.45 (4H, s, OCH2); 13C NMR (100 MHz, DMSO-d6): d 192.12
(C@O), 159.23 (C-3), 137.52 (C-1), 129.99 (C-6), 122.50 (C-5),
121.72 (C-4), 112.59 (C-2), 68.30 (OCH2); MS: m/z 293 (M + Na,
100%), 271 (M + 1, 26%), 257 (79%), 256 (22%), 253 (8%), 166 (8%),
149 (13%), 135 (21%), 121 (28%), 107 (34%); Anal. Calc. for
The compound 2f was prepared by reacting 3-hydroxybenzal-
dehyde 1 (1.22 g, 0.01 mol) with 1,10-dibromodecane (1.50 g,
0.005 mol) under similar conditions as used earlier for 2a.
2f: Yield (2.4 g, 62%); light brown solid; m.p. 59–61 °C; IR (KBr):
tmax cmꢀ1 3078 (aromatic C–H), 2924 (methylene C–H), 2852,
2755 (aldehyde C–H), 1680 (C@O); UV–Vis (MeOH): kmax (nm)
324, 264; 1H NMR (400 MHz, CDCl3): d 9.97 (2H, s, CHO), 7.44
(2H, brs, H-2), 7.43 (2H, brs, H-6), 7.38 (2H, d, J = 0.64 Hz, H-5),
7.17 (2H, m, H-4), 4.01 (4H, t, Jvic = 6.5 Hz, OCH2), 1.80 (4H, quintet,
Jvic = 6.6 Hz, OCH2CH2), 1.45 (4H, t, Jvic = 6.5 Hz, OCH2CH2CH2), 1.34
(8H, m, OCH2CH2CH2CH2); 13C NMR (100 MHz, DMSO-d6): d 192.25
(C@O), 159.71 (C-3), 137.76 (C-1), 129.99 (C-6), 123.35 (C-5),
121.98 (C-4), 112.71 (C-2), 68.28 (OCH2), 29.46 (OCH2CH2), 29.32
(OCH2CH2CH2), 29.11 (OCH2CH2CH2CH2), 25.99 (OCH2CH2CH2CH2
CH2); MS: m/z 405 (M + Na, 91%), 383 (M + 1, 79%), 334 (100%),
261 (21%), 256 (31%), 247 (8%), 246 (13%), 243 (23%), 173 (7%),
135 (31%), 121 (29%), 105 (22%); Anal. Calc. for C24H30O4: Calc. C,
75.39%, H, 7.85%; Found: C, 75.32%, H, 7.89%.
C16H14O4: Calc. C, 71.11%, H, 5.11%; Found: C, 71.08%, H, 5.15%.
4.2. Synthesis of 3,30-[butane-1,3-diylbis (oxy)] dibenzaldehyde 2b
The compound 2b was prepared by reacting 3-hydroxybenzal-
dehyde
1 (0.01 mol, 1.22 g) with 1,4-dibromobutane (1.12 g,
0.005 mol) under the similar conditions as used earlier for 2a.
The physical and spectral data of 2b was found to be consistent
as reported in literature [17].
4.3. Synthesis of 3,30-[pentane-1,5-diylbis (oxy)] dibenzaldehyde 2c
The compound 2c was prepared from the reaction of 3-
hydroxybenzaldehyde 1 (1.22 g, 0.01 mol) with 1,5-dibromopen-
tane (1.14 g, 0.005 mol) under similar conditions as used earlier
for 2a.
The physical and spectral data of 2c was found to be consistent
as reported in literature [17].
4.7. Synthesis of 3,30-[dodecane-1,12-diylbis (oxy)]dibenzaldehyde 2g
The compound 2g was synthesized from the reaction of 3-
hydroxybenzaldehyde 1 (1.22 g, 0.01 mol) with 1,12-dibromodo-
decane (1.64 g, 0.005 mol) under the same conditions as described
earlier for 2a.
4.4. Synthesis of 3,30-[hexane-1,6-diylbis (oxy)]dibenzaldehyde 2d
2g: Yield (2.5 g, 60%); grey solid; m.p. 57–59 °C; IR (KBr): tmax
cmꢀ1 3081 (aromatic C–H), 2938, 2920 (methylene C–H), 2850,
2759 (aldehyde C–H), 1681 (C@O); UV–Vis (MeOH): kmax (nm)
338, 258; 1H NMR (400 MHz, CDCl3): d 9.89 (2H, s, CHO), 7.37
(2H, brs, H-2), 7.36 (2H, t, J = 1.1 Hz, H-6), 7.30 (2H, d, J = 2.0 Hz,
H-5), 7.09 (2H, m, H-4), 3.93 (4H, t, Jvic = 6.5 Hz, OCH2), 1.74 (4H,
quintet, Jvic = 6.7 Hz, OCH2CH2), 1.40 (4H, t, Jvic = 6.4 Hz,
OCH2CH2CH2), 1.27 (12H, m, OCH2CH2CH2CH2CH2CH2); 13C NMR
(100 MHz, DMSO-d6): d 192.26 (C@O), 159.72 (C-3), 137.77 (C-1),
129.99 (C-6), 123.34 (C-5), 121.99 (C-4), 112.72 (C-2), 68.30
(OCH2), 29.55 (OCH2CH2), 29.35 (OCH2CH2CH2), 29.13 (OCH2CH2
CH2CH2), 29.12 (OCH2CH2CH2CH2CH2), 26.00 (OCH2CH2CH2CH2CH2
CH2); MS: m/z 433 (M + Na, 87%), 426 (13%), 412 (30%), 411 (M + 1,
95%), 348 (10%), 335 (25%), 334 (100%), 318 (5%), 289 (18%), 271
(19%), 274 (12%), 257 (18%), 173 (5%), 161 (4%), 147 (8%), 123
(15%), 111 (17%); Anal. Calc. for C26H34O4: Calc. C, 76.09%, H,
8.29%; Found: C, 76.13%, 8.24%.
The compound 2d was synthesized by reacting 3-hydroxybenz-
aldehyde 1 (1.22 g, 0.01 mol) and 1,6-dibromohexane (1.21 g,
0.005 mol) under similar conditions as used earlier for 2a.
2d: Yield (2.1 g, 64%); grey solid; m.p. 60–62 °C; IR (KBr): tmax
cmꢀ1 3064 (aromatic C–H), 2942 (methylene C–H), 2864, 2717
(aldehyde C–H), 1696 (C@O); UV–Vis (MeOH): kmax (nm) 338,
274; 1H NMR (400 MHz, DMSO-d6): d 9.97 (2H, s, CHO), 7.46 (2H,
d, Jp = 0.6 Hz, H-2), 7.44 (2H, t, J = 1.2 Hz, H-6), 7.38 (2H, d,
J = 2.1 Hz, H-5), 7.17 (2H, m, H-4), 4.03 (4H, t, Jvic = 6.4 Hz, OCH2),
1.85 (4H, t, Jvic = 6.4 Hz, OCH2CH2), 1.57 (4H, quintet, Jvic = 6.4 Hz,
OCH2CH2CH2); 13C NMR (100 MHz, DMSO-d6): d 192.37 (C@O),
159.13 (C-3), 137.51 (C-1), 130.04 (C-6), 122.20 (C-5), 121.16 (C-
4), 113.35 (C-2), 67.60 (OCH2), 28.51 (OCH2CH2), 25.23
(OCH2CH2CH2); MS: m/z 349 (M + Na, 100%), 327 (M + 1, 26%),
309 (8%), 257 (4%), 227 (8%), 203 (5%), 177 (7%), 161 (6%), 140
(4%), 123 (7%), 116 (4%), 107 (9%); Anal. Calc. for C20H22O4: Calc.
C, 73.61%, H, 6.74%; Found: C, 73.54%, H, 6.70%.
4.8. Synthesis of 2,20-[3,30-(ethane-1,2-diylbis(oxy)bis(3,1-phenylene))
bis(methan-1-yl-1-ylidene) bis (hydrazinecarbothioamide) 3a
4.5. Synthesis of 3,30-[octane-1,8-diylbis (oxy)]dibenzaldehyde 2e
A mixture of 2a (0.5 g, 0.00185 mol) and thiosemicarbazide
(0.337 g, 0.00370 mol) in dry EtOH (20 ml) and HCl (1.0 ml) was re-
fluxed for 4 h. The progress of the reaction was monitored by TLC
and after the completion of the reaction, the resulting mixture
was cooled in an ice bath to give a solid. The solid thus obtained
was filtered under suction dried and crystallized from MeOH to
yield pure compound 3a.
The compound 2e was obtained by treating 3-hydroxybenzal-
dehyde
1 (1.22 g, 0.01 mol) with 1,8-dibromooctane (1.36 g,
0.005 mol) under similar conditions as used earlier for 2a.
2e: Yield (2.3 g, 64%); brown solid; m.p. 65–67 °C; IR (KBr): tmax
cmꢀ1 3080 (aromatic C–H), 2938 (methylene C–H), 2854, 2756
(aldehyde C–H), 1679 (C@O); UV–Vis (MeOH): kmax (nm) 322,
269; 1H NMR (400 MHz, CDCl3): d 9.95 (2H, s, CHO), 7.45 (2H, s,
H-2), 7.42 (2H, t, J = 3.7 Hz, H-6), 7.35 (2H, brs, H-5), 7.18 (2H, m,
H-4), 4.03 (4H, t, Jvic = 6.4 Hz, OCH2), 1.80 (4H, quintet, Jvic = 6.8 Hz,
OCH2CH2), 1.47 (4H, m, OCH2CH2CH2), 1.37 (4H, m,
3a: Yield (0.6 g, 78%); dark brown solid; m.p. 150–152 °C; IR
(KBr): tmax cmꢀ1 3395, 3250, 3159 (N–H), 3027 (aromatic C–H),
2920, 2849 (methylene C–H), 1600 (C@N), 1179 (C@S); UV–Vis
(MeOH): kmax (nm) 321; 1H NMR (400 MHz, CDCl3): d 11.42 (2H,
s, 3-NH), 8.02 (2H, s, H-1), 7.62 (2H, brs, NH-b), 7.42 (2H, brs,
OCH2CH2CH2CH2); 13C NMR (100 MHz, DMSO-d6):
d 192.25
(C@O), 159.69 (C-3), 137.77 (C-1), 130.01 (C-6), 123.39 (C-5),
122.00 (C-4), 112.68 (C-2), 68.24 (OCH2), 29.26 (OCH2CH2), 29.10
(OCH2CH2CH2), 25.94 (OCH2CH2CH2CH2); MS: m/z 377 (M + Na,
100%), 355 (M + 1, 39%), 297 (18%), 269 (44%), 233 (43%), 219
(31%), 191 (32%), 177 (19%), 123 (9%), 107 (21%); Anal. Calc. for
NH-a
), 7.30 (4H, t, Jo = 7.8 Hz, H-20, 60), 7.21 (2H, d, Jo = 7.6 Hz, H-
50), 6.97 (2H, dd, Jm,o = 2.0, 7.9 Hz, H-40), 4.29 (4H, s, OCH2); 13C
NMR (100 MHz, DMSO-d6): d 177.98 (C@S), 158.69 (C-30), 142.52
(C@N), 135.18 (C-10), 129.15 (C-60), 120.8 (C-50), 116.22 (C-40),
111.33 (C-20), 67.42 (OCH2); MS: m/z 439 (M + Na, 21%), 417
(M + 1, 25%), 401 (8%), 400 (21%), 397 (100%), 356 (33%), 355
C
22H26O4: Calc. C, 74.57%, H, 7.34%; Found: C, 74.61%, H, 7.39%.

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M. Yusuf et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 97 (2012) 470–478
(15%), 341 (19%), 342 (28%), 326 (13%), 324 (22%), 315 (4%), 310
(17%), 146 (37%), 132 (18%), 105 (9%); Anal. Calc. for C18H20O2N6S2:
C, 51.92%, H, 4.80%, N, 20.19%, S, 15.38%; found: C, 52.19%, H, 4.84%,
N, 20.11%, S, 15.44%.
158.92 (C-30), 142.34 (C@N), 135.35 (C-10), 129.32 (C-60), 120.19
(C-50), 116.23 (C-40), 111.54 (C-20), 67.33 (OCH2), 28.70 (OCH2CH2),
25.36 (OCH2CH2CH2), MS: m/z 495 (M + Na, 21%), 473 (M + 1, 26%),
456 (8%), 397 (65%), 353 (24%), 351 (60%), 338 (52%), 323 (63%),
301 (62%), 293 (15%), 257 (89%), 255 (14%), 227 (18%), 223 (31%),
195 (36%), 191 (23%), 163 (40%), 149 (100%), 140 (91%), 116
(73%); Anal. Calc. for C23H28O2N6S2: C, 55.93%, H, 5.93%, N,
17.79%, S, 13.55%, found: C, 55.71%, H, 5.96%, N, 17.72%, S, 13.60%.
4.9. Synthesis of 2,20-(3,30-(butane-1,4-diylbis(oxy))bis(3,1-phenylene))
bis(methan-1-yl-1-ylidene)bis(hydrazinecarbothioamide) 3b
The compound 3b was prepared from the reaction of 2b (0.5 g,
0.00167 mol) with thiosemicarbazide (0.305 g, 0.0033 mol) under
the similar reaction conditions as described above for 3a.
4.12. Synthesis of 2,20-(3,30-(octane-1,8-diylbis(oxy))bis(3,1-phenylene))
bis(methan-1-yl-1-ylidene)bis(hydrazinecarbothioamide) 3e
3b: Yield (0.5 g, 68%); greyish yellow solid; m.p. 208–210 °C; IR
(KBr): tmax cmꢀ1 3390, 3238, 3154 (N–H), 3025 (aromatic C–H),
2937, 2870 (methylene C–H), 1600 (C@N), 1178 (C@S); UV–Vis
(MeOH): kmax (nm) 318; 1H NMR (400 MHz, DMSO-d6): d 11.42
(2H, s, 3-NH), 8.02 (2H, s, H-1), 7.76 (2H, brs, NH-b), 7.51 (2H, brs,
The compound 3e was obtained by reacting dibenzaldehyde 2e
(0.7 g, 0.0019 mol) with thiosemicarbazide (0.35 g, 0.0039 mol)
under the same reaction conditions as used for 3a.
3e: Yield (0.8 g, 81%), light brown solid; m.p. 212–214 °C; IR
(KBr): tmax cmꢀ1 3398, 3246, 3157 (N–H), 3025 (aromatic C–H),
2934, 2853 (methylene C–H), 1599 (C@N), 1179 (C@S); UV–Vis
(MeOH): kmax (nm) 362; 1H NMR (400 MHz, CDCl3): d 11.43 (2H,
s, 3-NH), 8.03 (2H, brs, H-1), 7.89 (2H, brs, NH-b), 7.61 (2H, brs,
NH-a
), 7.27 (4H, t, Jo = 7.3 Hz, H-20,60), 7.19 (2H, d, Jo = 7.6 Hz, H-
50), 6.92 (2H, dd, J = 1.8, 7.9 Hz, H-40), 4.08 (4H, brs, OCH2), 1.99
(4H, brs, OCH2CH2); 13C NMR (100 MHz, DMSO-d6): d 177.96
(C@S), 158.79 (C-30), 142.50 (C@N), 135.20 (C-10), 129.26 (C-60),
120.17 (C-50), 116.24 (C-40), 111.44 (C-20), 66.98 (OCH2), 25.42
(OCH2CH2); MS: m/z 467 (M + Na, 13%), 445 (M + 1, 6%), 401 (7%),
400 (18%), 397 (100%), 384 (6%), 384 (6%), 370 (4%), 369 (14%), 354
(15%), 352 (12%), 338 (16%), 295 (35%), 293 (21%), 293 (21%), 174
(37%), 132 (12%), 105 (13%); Anal. Calc. for C20H24O2N6S2: C,
54.05%, H, 5.40%, N, 18.91%, S, 14.41%; found: C, 53.84%, H, 5.44%,
N, 18.84%, S, 14.46%.
NH- a
), 7.29 (2H, brs, H-20), 7.27 (2H, t, Jo = 7.8 Hz, H-60), 7.21 (2H,
d, Jo = 7.7 Hz, H-50), 6.91 (d{dd}, 2H, Jm,o = 1.7, 8.1 Hz, H-40), 4.00
(4H, t, Jvic = 6.4 Hz, OCH2), 1.75 (4H, quintet, Jvic = 6.5 Hz, OCH2CH2),
1.48 (4H, quintet, Jvic = 6.4 Hz, OCH2CH2CH2), 1.43 (4H, Jvic = 3.2 Hz,
quintet, OCH2CH2CH2CH2); 13C NMR (100 MHz, DMSO-d6): d 177.98
(C@S), 158.88 (C-30), 142.62 (C@N), 135.10 (C-10), 129.22 (C-60),
119.93 (C-50), 116.14 (C-40), 111.54 (C-20), 67.41 (OCH2), 28.74
(OCH2CH2), 28.70 (OCH2CH2CH2), 25.45 (OCH2CH2CH2CH2); MS:
m/z 523 (M + Na, 100%), 501 (M + 1, 31%), 484 (11%), 425 (67%),
381 (24%), 379 (63%), 352 (53%), 351 (52%), 323 (64%), 367 (18%),
297 (33%), 269 (36%), 195 (39%), 191 (26%), 163 (47%), 149 (92%),
105 (72%); Anal. Calc. for C24H32 O2N6S2: C, 57.6%, H, 6.4%, N,
16.8%, S, 12.8%, found: C, 57.37%, H, 6.25%, N, 16.74%, S, 12.75%.
4.10. Synthesis of 2,20-(3,30-(pentane-1,5-diylbis(oxy))bis(3,1-
phenylene)) bis(methan-1-yl-1-ylidene)bis(hydrazinecarbothioamide) 3c
The compound 3c was obtained by reacting compound 2c (0.5 g,
0.0016 mol) with thiosemicarbazide (0.29 g, 0.003205 mol) under
the reaction conditions as used for 3a.
3c: Yield (0.5 g, 68%), dark brown solid; m.p. 212–214 °C; IR
(KBr): tmax cmꢀ1 3368, 3247, 3157 (N–H), 3025 (aromatic C–H),
2937, 2863 (methylene C–H), 1600 (C@N), 1177 (C@S); UV–Vis
(MeOH): kmax (nm) 323; 1H NMR (400 MHz, DMSO-d6): d 11.40
(2H, s, 3-NH), 8.03 (2H, s, H-1), 7.72 (2H, brs, NH-b), 7.49 (2H, brs,
4.13. Synthesis of 2,20-(3,30-(decane-1,10-diylbis(oxy))bis(3,1-
phenylene)) bis(methan-1-yl-1-ylidene)bis(hydrazinecarbothioamide) 3f
The compound 3f was prepared by treating 2f (0.5 g,
0.0013 mol) with thiosemicarbazide (0.23 g, 0.0026 mol) under
the similar conditions as used for 3a.
NH- a
), 7.27 (4H, t, Jo = 7.3 Hz, H-20, 60), 7.18 (2H, d, Jo = 7.5 Hz, H-
50), 6.91 (2H, dd, Jm,o = 2.3, 7.9 Hz, H-40), 4.11 (4H, brs, OCH2), 1.96
(4H, t, Jvic = 6.4 Hz, OCH2CH2), 1.43 (2H, brs, OCH2CH2CH2); 13C
NMR (100 MHz, DMSO-d6): d 177.98 (C@S), 158.89 (C-30), 142.62
(C@N), 135.39 (C-10), 129.33 (C-60), 120.17 (C-50), 116.19 (C-40),
111.49 (C-20), 67.41 (OCH2), 25.42 (OCH2CH2), 23.76 (OCH2CH2CH2);
MS: m/z 481 (M + Na, 24%), 459 (M + 1, 17%), 442 (9%), 398 (11%),
397 (32%), 384 (6%), 383 (67%), 368 (17%), 352 (13%), 307 (26%),
297 (35%), 257 (78%), 191 (27%), 163 (46%), 149 (100%), 132 (26%),
105 (19%); Anal. Calc for C22H26O2N6S2: C, 55.02%, H, 5.67%, N,
18.34%, S, 13.97%; found: C, 55.24%, H, 5.62%, N, 18.41%, S, 13.92%.
3f: Yield (0.5 g, 72%), creamish solid; m.p. 178–180 °C; IR (KBr):
tmax cmꢀ1 3398, 3245, 3158 (N–H), 3027 (aromatic C–H), 2921,
2850 (methylene C–H), 1600 (C@N), 1179 (C@S); UV–Vis (MeOH):
kmax (nm) 361; 1H NMR (400 MHz, DMSO-d6): d 11.41 (2H, s,
3-NH), 8.02 (2H, s, H-1), 7.79 (2H, brs, NH-b), 7.52 (2H, brs, NH-
a
), 7.28 (2H, brs, H-20), 7.25 (2H, d, Jo = 7.7 Hz, H-60), 7.18 (2H, d,
Jo = 8.0 Hz, H-50), 6.90 (2H, dd, Jm,o = 2.0, 8.0 Hz, H-40), 3.98 (4H, t,
Jvic = 6.4 Hz, OCH2), 1.77 (4H, quintet, Jvic = 6.5 Hz, OCH2CH2), 1.45
(4H, quintet, Jvic = 6.4 Hz, OCH2CH2CH2), 1.34 (8H, m,
OCH2CH2CH2CH2CH2); 13C NMR (100 MHz, DMSO-d6): d 177.96
(C@S), 158.91 (C-30), 142.47 (C@N), 135.22 (C-10), 129.24 (C-60),
120.01 (C-50), 116.14 (C-40), 111.35 (C-20), 67.42 (OCH2), 28.92
(OCH2CH2), 28.79 (OCH2CH2CH2), 28.73 (OCH2CH2CH2CH2), 25.51
(OCH2CH2CH2CH2CH2); MS: m/z 551 (M + Na, 29%), 529 (M + 1,
36%), 509 (100%), 453 (21%), 397 (69%), 293 (25%), 274 (33%),
257 (73%), 228 (13%), 215 (24%), 179 (8%), 159 (62%), 149 (19%),
117 (44%); Anal. Calc. for C26H36O2N6S2: C, 59.09%, H, 6.81%, N,
15.90%, S, 12.12%; found: C, 59.32%, H, 6.85%, N, 15.84%, S, 12.08%.
4.11. Synthesis of 2,20-(3,30-(hexane-1,6-diylbis(oxy))bis(3,1-phenylene))
bis(methan-1-yl-1-ylidene)bis(hydrazinecarbothioamide) 3d
The compound 3d was prepared from the reaction of 2d (0.5 g,
0.0015 mol) with thiosemicarbazide (0.27 g, 0.0030 mol) under the
reaction conditions as described for 3a.
3d: Yield (0.5 g, 69%), dark brown solid; m.p. 204–206 °C; IR
(KBr): tmax cmꢀ1 3368, 3247, 3157 (N–H), 3025 (aromatic C–H),
2937, 2863 (methylene C–H), 1600 (C@N), 1177 (C@S), UV–Vis
(MeOH): kmax (nm) 320; 1H NMR (400 MHz, CDCl3): d 11.40 (2H,
s, 3-NH), 8.02 (2H, s, H-1), 7.69 (2H, brs, NH-b), 7.56 (2H, brs,
4.14. Synthesis of 2,20-(3,30-(dodecane-1,12-diylbis(oxy))bis(3,1-
phenylene))bis(methan -1-yl-1-ylidene)bis(hydrazinecarbothioamide)
3g
NH-a
), 7.27 (4H, t, Jo = 7.9 Hz, H-20, 60), 7.19 (2H, d, Jo = 7.6 Hz, H-
50), 6.91 (2H, dd, J = 2.4, 8.0 Hz, H-40), 4.00 (4H, t, Jvic = 6.4 Hz,
OCH2), 1.43 (4H, t, Jvic = 6.4 Hz, OCH2CH2), 1.25 (4H, m,
OCH2CH2CH2); 13C NMR (100 MHz, DMSO-d6): d 177.92 (C@S),
The compound 3g was prepared from the reaction of 2g (0.7 g,
0.0017 mol) with thiosemicarbazide (0.31 g, 0.0034 mol) under
similar reaction conditions as used for 3a.

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477
3g: Yield (0.8 g, 85%), creamish solid; m.p. 168–170 °C; IR (KBr):
tmax cmꢀ1 3395, 3250, 3159 (N–H), 3027 (aromatic C–H), 2920,
2849 (methylene C–H), 1600 (C@N), 1179 (C@S); UV–Vis (MeOH):
kmax (nm) 356; 1H NMR (400 MHz, DMSO-d6): d 11.41 (2H, s,
3-NH), 8.02 (2H, brs, H-1), 8.02 (2H, brs, NH-b), 7.73 (2H, s, NH-
(49%), 396 (66%), 372 (21%), 355 (50%), 337 (21%), 313 (45%), 295
(37%), 238 (8%), 178 (13%), 177 (100%),149 (18%), 135 (22%), 107
(43%); Anal. Calc. for C28H32O6N6S2: C, 54.90%, H, 5.22%, N,
13.72%, S, 10.45%; found: C, 55.69%, H, 5.26%, N, 13.77%, S,
10.49%.
a
), 7.32 (2H, brs, H-20), 7.26 (2H, t, J = 7.8 Hz, H-60), 7.19 (2H, d,
Jo = 7.6 Hz, H-50), 6.88 (2H, d{dd}, Jp,m,o= 1.2, 2.4, 7.2 Hz, H-40),
3.98 (4H, t, Jvic = 6.4 Hz, OCH2), 1.75 (4H, quintet, Jvic = 6.5, OCH2
CH2), 1.43 (4H, quintet, Jvic = 6.8 Hz, OCH2CH2CH2), 1.29 (12H, m,
4.17. Synthesis of N,N0-(5,50-(3,30-(pentane-1,5-diylbis(oxy))bis(3,1-
phenylene))bis(4-acetyl-4,5-dihydro-1,3,4-thiadiazole-5,2-
diyl))diacetamide 4c
OCH2CH2CH2CH2CH2CH2); 13C NMR (100 MHz, DMSO-d6):
d
177.95 (C = S), 158.90 (C-30), 142.55 (C@N), 135.16 (C-10), 129.23
(C-60), 119.95 (C-50), 116.12 (C-40), 111.57 (C-20), 67.44 (OCH2),
28.98 (OCH2CH2), 28.80 (OCH2CH2CH2), 28.73 (OCH2CH2CH2CH2),
26.59 (OCH2CH2CH2CH2CH2), 25.51 (OCH2 CH2CH2CH2CH2CH2);
MS: m/z 579 (M + Na, 44%), 557 (M + 1, 29%), 568 (12%), 510
(35%), 509 (100%), 492 (8%), 481 (19%), 453 (12%), 437 (22%), 407
(16%), 390 (5%), 331 (43%), 293 (10%), 275 (32%), 274 (34%), 257
(75%), 228 (11%), 215 (8%), 179 (6%), 149 (14%), 117 (11%); Anal.
Calc. for C28H40O2N6S2: C, 60.43%, H, 7.19%, N, 15.10%, S, 11.51%;
found: C, 60.19%, H, 7.24%, N, 15.16%, S, 11.55%.
The compound 4c was obtained by treating 3c (0.5 g,
0.00109 mol) with acetic anhydride (25 ml) under the similar con-
ditions as used earlier for 4a.
4c: Yield (0.6 g, 88%); brown solid; m.p. 84–86 °C; IR (KBr): tmax
cmꢀ1 3162 (N–H), 3063 (aromatic C–H), 2936, 2873 (methylene
C–H), 1695, 1639 (C@O), 1606 (C@N); UV–Vis (MeOH): kmax (nm)
1
341, 272; H NMR (400 MHz, DMSO-d6): d 11.61 (2H, s, 1000-NH),
7.17 (2H, t, J = 7.9 Hz, H-60), 6.86 (2H, d, Jm = 1.7 Hz, H-50), 6.76
(2H, brs, H-20), 6.73 (2H, brs, H-40), 6.70 (2H, s, H-2), 3.98 (4H,
brs, OCH2), 2.23 (6H, s, 3000-CH3), 2.13 (6H, s, 200-CH3), 1.94 (4H,
brs, OCH2CH2), 1.47 (2H, brs, OCH2CH2CH2); 13C NMR (100 MHz,
DMSO-d6): d 169.09 (2000-C@O), 167.38 (100-C@O), 158.84 (C-30),
146.09 (C@N), 142.74 (C-10), 129.52 (C-60), 116.80 (C-50), 113.43
(C-40 111.38 (C-20), 67.23 (OCH2), 65.84 (C-2), 28.73 (OCH2CH2),
25.46 (OCH2CH2), 21.81 (3000-CH3), 20.48 (200-CH3); MS: m/z 649
(M + Na, 93%), 627 (M + 1, 47%), 585 (14%), 583 (21%), 543 (12%),
526 (31%), 484 (19%), 428 (57%), 386 (34%), 327 (44%), 285 (51%),
177 (100%), 163 (23%), 149 (7%), 135 (39%), 121 (21%), 107 (49%);
Anal. Calc. for C29H34O6N6S2: C, 55.59%, H, 5.43%, N, 13.41%, S,
10.22%; found: C, 55.37%, H, 5.38%, N, 13.36%, S, 10.26%.
4.15. Synthesis of N,N0-(5,50-(3,30-(ethane-1,2-diylbis(oxy))bis(3,1-
phenylene))bis(4-acetyl-4,5-dihydro-1,3,4-thiadiazole-5,2-
diyl))diacetamide 4a
A mixture of 3a (0.5 g, 0.0012 mol) and acetic anhydride (25 ml)
was refluxed for 10 h and the progress of reaction was monitored
by TLC. The resulting reaction mixture was poured over ice to ob-
tain a solid product which was filtered under suction and finally
crystallized from EtOH to yield pure compound 4a.
4ª: Yield (0.5 g, 71%); brown solid; m.p. 85–87 °C; IR (KBr): tmax
cmꢀ1 3227, 3161 (N–H), 3062 (aromatic C–H), 2932 (methylene
C–H), 1695 (C@O), 1606 (C@N); UV–Vis (MeOH): kmax (nm) 343,
4.18. Synthesis of N,N0-(5,50-(3,30-(hexane-1,6-diylbis(oxy))bis(3,1-
phenylene))bis(4-acetyl-4,5-dihydro-1,3,4-thiadiazole-5,2-diyl))
diacetamide 4d
1
276; H NMR (400 MHz, DMSO-d6): d 11.64 (2H, s, 1000-NH), 7.25
(2H, t, J = 8.2 Hz, H-60), 6.89 (2H, brs, H-50), 6.86 (2H, d, Jo = 4.2 Hz,
H-40), 6.84 (2H, brs, H-20), 6.74 (2H, s, H-2), 4.30 (4H, s, OCH2), 2.25
(6H, s, 3000-CH3), 2.05 (6H, s, 200-CH3); 13C NMR (100 MHz, DMSO-
d6): d 169.09 (2000-C@O), 167.29 (100-C@O), 158.85 (C-30), 146.12
(C@N), 142.73 (C-10), 129.52 (C-60), 116.80 (C-50), 113.43 (C-40),
111.37 (C-20), 67.32 (OCH2), 65.91 (C-2), 21.73 (3000-CH3), 20.74
(200-CH3), MS: m/z 607 (M + Na, 100%), 585 (M + 1, 49%), 572
(24%), 571 (81%), 541 (11%), 484 (26%), 442 (19%), 386 (53%), 285
(47%), 179 (5%), 121 (19%), 107 (43%); Anal. Calc. for C26H28O6N6S2:
C, 53.42%, H, 4.79%, N, 14.38%, S, 10.95%; found C, 53.63%, H, 4.75%,
N, 14.33%, S, 10.99%.
The compound 4d was prepared from the reaction of 3d (0.5 g,
0.00106 mol) with acetic anhydride (25 ml) under the similar con-
ditions as described earlier for 4a.
4d: Yield (0.5 g, 74%); brown solid; m.p. 100–102 °C; IR (KBr):
tmax cmꢀ1 3161 (N–H), 3062 (aromatic C–H), 2937, 2865 (methy-
lene C–H), 1698, 1638 (C@O), 1606 (C@N); UV–Vis (MeOH): kmax
(nm) 344, 269; 1H NMR (400 MHz, DMSO-d6): d 11.57 (2H, s,
1000-NH), 7.22 (2H, t, J = 7.8 Hz, H-60), 6.82 (2H, d, Jo = 6.7 Hz, H-50),
6.78 (2H, d, Jo = 7.5 Hz, H-40), 6.76 (2H, s, H-20), 6.70 (2H, s, H-2),
3.95 (4H, t, Jvic = 6.2 Hz, OCH2), 2.25 (6H, s, 3000-CH3), 2.04 (6H, s,
200-CH3), 1.79 (4H, brs, OCH2CH2), 1.53 (4H, brs, OCH2CH2CH2);
13C NMR (100 MHz, DMSO-d6): d 169.04 (2000-C@O), 167.37 (100-
C@O), 158.84 (C-30), 146.12 (C@N), 142.48 (C-10), 129.52 (C-60),
116.85 (C-50), 113.43 (C-40), 111.37 (C-20), 67.28 (OCH2), 65.90
(C-2), 28.63 (OCH2CH2), 25.33 (OCH2CH2CH2), 21.76 (3000-CH3),
20.75 (200-CH3); MS: m/z 683 (M + Na, 100%), 641 (M + 1, 43%),
599 (52%), 562 (27%), 557 (14%), 540 (12%), 506 (39%), 484 (18%),
475 (33%), 453 (21%), 442 (23%), 424 (50%), 383 (19%), 349 (36%),
327 (23%), 280 (12%), 238 (35%), 221 (22%), 194 (7%), 173 (18%),
155 (59%), 140 (12%), 116 (17%); Anal. Calc. for C30H36O6N6S2: C,
56.25%, H, 5.62%, S, 10.00%, N, 13.12%; found: C, 56.47%, H, 5.59%,
S, 9.96%, N, 13.17%.
4.16. Synthesis of N,N0-(5,50-(3,30-(butane-1,4-diylbis(oxy))bis(3,1-phe-
nylene)) bis(4-acetyl-4,5-dihydro-1,3,4-thiadiazole-5,2-diyl))
diacetamide 4b
The compound 4b was prepared by reacting 3b (0.5 g,
0.00113 mol) with acetic anhydride (25 ml) under the similar con-
ditions as described earlier for 4a.
4b: Yield (0.5 g, 73%); brown solid; m.p. 78–80 °C; IR (KBr): tmax
cmꢀ1 3164 (N-H), 3065 (aromatic C–H), 2943, 2875 (methylene
C–H), 1695, 1640 (C@O), 1605 (C@N); UV–Vis (MeOH): kmax (nm)
1
342, 278; H NMR (400 MHz, DMSO-d6): d 11.59 (2H, s, 1000-NH),
7.23 (2H, t, J = 7.9 Hz, H-60), 6.82 (2H, d, Jo = 1.7 Hz, H-50), 6.80
(2H, brs, H-20), 6.80 (2H, d, J = 1.4 Hz, H-40), 6.72 (2H, s, H-2),
4.01 (4H, brs, OCH2), 2.24 (6H, s, 3000-CH3), 2.07 (6H, s, 200-CH3),
1.94 (4H, brs, OCH2CH2); 13C NMR (100 MHz, DMSO-d6): d 169.13
(2000-C@O), 167.30 (100-C@O), 158.75 (C-30), 146.09 (C@N), 142.75
(C-10), 129.68 (C-60), 116.87 (C-50), 113.47 (C-40), 111.35 (C-20),
67.00 (OCH2), 65.77 (C-2), 25.41 (OCH2CH2), 21.81 (3000-CH3),
4.19. Synthesis of N,N0-(5,50-(3,30-(octane-1,8-diylbis(oxy))bis(3,1-
phenylene))bis(4-acetyl-4,5-dihydro-1,3,4-thiadiazole-5,2-diyl))
diacetamide 4e
The compound 4e was obtained by reacting 3e (0.5 g,
0.001 mol) with acetic anhydride (25 ml) under the similar condi-
tions as used earlier for 4a.
20.48 (200-CH3);
635 (M + Na, 37%), 613 (M + 1, 53%), 571
MS: m/z
(82%), 569 (9%), 529 (32%), 512 (22%), 470 (18%), 456 (19%), 414

478
M. Yusuf et al. / Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 97 (2012) 470–478
4e: Yield (0.6 g, 89%); creamish solid; m.p. 85–87 °C; IR (KBr):
4g: Yield (0.5 g, 77%), light brown solid; m.p. 64–66 °C; IR (KBr):
tmax cmꢀ1 3162 (N-H), 3065 (aromatic C-H), 2926, 2853 (methy-
lene C-H), 1698, 1639 (C@O), 1606 (C@N); UV–Vis (MeOH): kmax
tmax cmꢀ1 3160 (N–H), 3065 (aromatic C–H), 2934, 2856 (methy-
lene C–H), 1697, 1639 (C@O), 1607 (C@N); UV–Vis (MeOH): kmax
(nm) 341, 273; 1H NMR (400 MHz, DMSO-d6): d 11.61 (2H, s,
1000-NH), 7.19 (2H, t, Jo = 7.9 Hz, H-60), 6.78 (2H, brs, H-50), 6.76
(2H, brs, H-20), 6.74 (2H, d, Jm = 2.2 Hz, H-40), 6.72 (2H, s, H-2),
3.90 (4H, t, Jvic = 6.4 Hz, OCH2), 2.20 (6H, s, 3000-CH3), 2.03 (6H, s,
200-CH3), 1.71 (4H, quintet, Jvic = 6.7 Hz, OCH2CH2), 1.42 (4H, brs,
OCH2CH2CH2), 1.36 (4H, brs, OCH2CH2CH2CH2); 13C NMR
1
(nm) 343, 272; H NMR (400 MHz, DMSO-d6): d 11.54 (2H, s, 1000-
NH), 7.17 (2H, t, Jo = 7.9 Hz, H-60), 6.77 (2H, d, Jm = 2.4 Hz, H-50),
6.75 (2H, d, Jm = 3.6 Hz, H-40), 6.72 (2H, brs, H-20), 6.67 (2H, s, H-
2), 3.88 (4H, t, Jvic = 6.4 Hz, OCH2), 2.22 (6H, s, 3000-CH3), 2.03 (6H,
s, 200-CH3), 1.69 (4H, quintet, Jvic = 6.4 Hz, OCH2CH2), 1.37 (4H,
brs, OCH2CH2CH2), 1.26 (12H, s, OCH2CH2CH2CH2CH2CH2); 13C
NMR (100 MHz, DMSO-d6): d 169.04 (2000-C@O), 167.37 (100-C@O),
158.87 (C-30), 146.12 (C@N), 142.47 (C-10), 129.51 (C-60), 116.82
(C-50), 113.39 (C-40), 111.38 (C-20), 67.39 (OCH2), 65.91 (C-2),
28.98 (OCH2CH2), 28.82 (OCH2CH2CH2), 28.70 (OCH2CH2CH2CH2),
25.50 (OCH2CH2CH2CH2CH2), 24.22 (OCH2CH2CH2CH2CH2CH2),
22.38 (3000-CH3), 21.76 (200-CH3); MS: m/z 747 (M + Na, 28%), 725
(M + 1, 94%), 684 (40%), 683 (100%), 641 (20%), 624 (21%), 582
(10%), 568 (16%), 526 (24%), 508 (48%), 484 (9%), 467 (13%), 407
(11%), 390 (7%), 362 (4%), 334 (3%), 271 (5%), 238 (6%), 221
(14%), 179 (7%), 155 (22%), 116 (8%); Anal. Calc. for C36H48O6N6S2,
C, 59.66%, H, 6.62%, S, 8.83%, N, 11.60%; found: C, 59.43%, H, 6.65%,
S, 8.86%, N, 11.56%.
(100 MHz, DMSO-d6):
d
169.07 (2000-C@O), 167.29 (100-C@O),
158.85 (C-30), 146.09 (C@N), 142.64 (C-10), 129.58 (C-60), 116.80
(C-50), 113.44 (C-40), 111.37 (C-20), 67.37 (OCH2), 65.84 (C-2),
28.75 (OCH2CH2), 25.46 (OCH2CH2CH2), 25.32 (OCH2CH2CH2CH2),
22.42 (3000-CH3), 21.78 (200-CH3); MS: m/z 691 (M + Na, 100%), 668
(M + 1, 51%), 625 (54%), 585 (21%), 571 (78%), 568 (19%), 526
(23%), 470 (16%), 452 (24%), 393 (13%), 369 (49%), 294 (9%), 221
(21%), 238 (9%), 179 (16%), 155 (28%), 116 (31%); Anal. Calc. for
C
32H40O6N6S2: C, 57.48%, H, 5.98%, S, 9.58%, N, 12.57%; found: C,
57.26%, H, 5.94%, S, 9.61%, N, 12.45%.
4.20. Synthesis of N,N0-(5,50-(3,30-(decane-1,10-diylbis(oxy))bis(3,1-
phenylene))bis(4-acetyl-4,5-dihydro-1,3,4-thiadiazole-5,2-diyl))
diacetamide 4f
Acknowledgment
The compound 4f was prepared from the reaction of 3f (0.5 g,
0.00095 mol) with acetic anhydride (25 ml) under the similar con-
ditions as used earlier for 4a.
Authors are highly thankful to DST (SERC, Fast Track Scheme
No. SR/FT/CS-041/2010), New Delhi for providing the financial sup-
port for this research work.
4f: Yield (0.6 g, 77%), brown solid; m.p. 78–80 °C; IR (KBr): tmax
cmꢀ1 3160 (N–H), 3065 (aromatic C–H), 2934, 2856 (methylene
C–H), 1697, 1639 (C@O), 1607 (C@N); UV–Vis (MeOH): kmax (nm)
References
1
342, 271; H NMR (400 MHz, DMSO-d6): d 11.61 (2H, s, 1000-NH),
[1] M.H. Shih, C.L. Wu, Tetrahedron 61 (2005) 10917.
[2] V.A. Ogurtsov, O.A. Rakitin, C.W. Rees, A.A. Smolentsev, Mandeleev Commun.
(2005).
[3] D.J. Wilkins, 1,2,3-Thiadiazoles, in: Comprehensive Heterocyclic Chemistry III,
Springer, Berlin, 2008 (467 Chapter 5.07).
[4] A.R. Katritzky, C.W. Rees, Mathy, in: K.T. Potts (Ed.), Comprehensive
Heterocyclic Chemistry: The Structure, Reactions, Synthesis and Uses of
Heterocyclic Compounds, vol. 6(4B), Pergamon Press, New York, 1981, pp.
548–9.
[5] Nizamuddin, S. Alauddin, H.C. Gupta, M.K. Srivastav, Ind. J. Chem. 41B (2002)
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(1994) 65.
[8] A.R. Farghaly, E.D. Clercq, H. El-Kashef, Arkivoc 10 (2006) 137.
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[10] V. Jatav, P. Mishra, S. Kashaw, Eur. J. Med. Chem. 43 (9) (2008) 1945.
[11] H. Ying, Y. Hu, Q. He, R. Li, B. Yang, Eur. J. Med. Chem. 42 (2) (2007) 226.
[12] C.T. Supuran, B.W. Clare, Eur. J. Med. Chem. 34 (1) (1999) 41.
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[14] (a) M. Yusuf, P. Jain, Arab. J. Chem. 5 (2012) 93;
7.19 (2H, t, J = 7.9 Hz, H-60), 6.78 (2H, brs, H-50), 6.76 (2H, s,
H-20), 6.74 (2H, d, Jm = 2.2 Hz, H-40), 6.70 (2H, s, H-2), 3.90 (4H, t,
Jvic = 6.4 Hz, OCH2), 2.20 (6H, s, 3000-CH3), 2.03 (6H, s, 200-CH3), 1.71
(4H, quintet, Jvic = 6.7 Hz, OCH2CH2), 1.42 (4H, brs, OCH2CH2CH2),
1.36 (8H, brs, OCH2CH2CH2CH2CH2); 13C NMR (100 MHz, DMSO-
d6): d 169 (2000-C@O), 167.32 (100-C@O), 158.83 (C-30), 146.19
(C@N), 142.48 (C-10), 129.52 (C-60), 116.85 (C-50), 113.38 (C-40),
111.37 (C-20), 67.29 (OCH2), 65.90 (C-2), 29.95 (OCH2CH2), 28.71
(OCH2CH2CH2), 25.53 (OCH2CH2CH2CH2), 22.42 (OCH2CH2
CH2CH2CH2), 22.39 (3000-CH3), 21.73 (200-CH3); MS: m/z 719
(M + Na, 31%), 697 (M + 1, 82%), 655 (100%), 612 (11%), 598
(24%), 556 (18%), 554 (13%), 542 (22%), 327 (26%), 238 (8%), 221
(19%), 179 (8%), 155 (29%), 117 (13%), 116 (9%); Anal. Calc. for
C34H44O6N6S2, C, 58.62%, H, 6.32%, S, 9.19%, N, 12.06%; found: C,
58.85%, H, 6.36%, S, 9.22%, N, 12.02%.
(b) M. Yusuf, P. Jain, Asian J. Res. Chem. 4 (7) (2011) 1103.
[15] A.H.M. Elwahy, J. Chem. Res. (1999) 602.
[16] K.S. Pandey, N. Khan, Arch. Pharm. Chem. Life Sci. 341 (2008) 418.
[17] A. Kamal, M.S. Malik, S. Bajee, S. Azeeza, S. Faazil, S. Ramakrishna, V.G.M.
Naidu, M.V.P.S. Vishnuwardhan, Eur. J. Med. Chem. 46 (2011) 3274.
4.21. Synthesis of N,N0-(5,50-(3,30-(dodecane-1,12-diylbis(oxy)) bis(3,1-
phenylene))bis(4-acetyl-4,5-dihydro-1,3,4-thiadiazole-5,2-diyl))
diacetamide 4g
The compound 4g was synthesized by treating bisthiosemicar-
bazone 3g (0.5 g, 0.0009 mol) with acetic anhydride under the sim-
ilar conditions as described earlier for 4a.