Synthesis, antifungal and antibacterial activity of calix[4]arene-based 1,3,4-oxadiazole derivatives

Article abstract of DOI:10.1002/jccs.201900425

We describe the synthesis of some novel p-tert-butylcalix[4]arene-based (5-aryl-1,3,4-oxadiazol-2-yl)2-chloroethanethioate derivatives (4a–e). These compounds were synthesized by the reaction of tetra-tert-butyl calix[4]arene (1) with (5-aryl-1,3,4-oxadiazol-2-yl)2-chloroethanethioate (3a–e) in the presence of potassium carbonate as a weak base and dry acetone as the solvent. All the newly synthesized calix[4]arene derivatives were characterized by elemental analysis and various spectroscopic methods such as FT-IR, ¹H NMR,¹³C NMR, DEPT, and ESI-MS. The synthesized compounds were tested in vitro for their antibacterial and antifungal activities against Escherichia coli and Aspergillus fumigates in comparison with enrofloxacin and amphotericin as reference drugs, which are normally used for treating such infections. The synthesized compounds showed different inhibition zones against the tested bacteria and fungi. Compound 4c was found to be most effective against A. fumigates, whereas compound 4e was found to be equally effective against E. coli and A. fumigates.

Full text of DOI:10.1002/jccs.201900425

Received: 26 November 2019
DOI: 10.1002/jccs.201900425
Revised: 17 February 2020
Accepted: 24 February 2020
A R T I C L E
Synthesis, antifungal and antibacterial activity of calix[4]
arene-based 1,3,4-oxadiazole derivatives
Zahra Dono Gezelbash
| Karim Akbari Dilmaghani
Department of Organic Chemistry,
Faculty of Chemistry, Urmia University,
Urmia, Iran
Abstract
We describe the synthesis of some novel p-tert-butylcalix[4]arene-based
(5-aryl-1,3,4-oxadiazol-2-yl)2-chloroethanethioate derivatives (4a–e). These
compounds were synthesized by the reaction of tetra-tert-butyl calix[4]arene
(1) with (5-aryl-1,3,4-oxadiazol-2-yl)2-chloroethanethioate (3a–e) in the pres-
ence of potassium carbonate as a weak base and dry acetone as the solvent. All
the newly synthesized calix[4]arene derivatives were characterized by elemen-
Correspondence
Karim Akbari Dilmaghani, Department of
Organic Chemistry, Faculty of Chemistry,
Urmia University, Urmia, 57159, Iran.
Email: k.adilmaghani@urmia.ac.ir
tal analysis and various spectroscopic methods such as FT-IR, H NMR,13C
1
Funding information
Urmia University
NMR, DEPT, and ESI-MS. The synthesized compounds were tested in vitro for
their antibacterial and antifungal activities against Escherichia coli and Asper-
gillus fumigates in comparison with enrofloxacin and amphotericin as refer-
ence drugs, which are normally used for treating such infections. The
synthesized compounds showed different inhibition zones against the tested
bacteria and fungi. Compound 4c was found to be most effective against A.
fumigates, whereas compound 4e was found to be equally effective against E.
coli and A. fumigates.
K E Y W O R D S
antibacterial activity, antifungal activity, in vitro, S-(5-aryl-1,3,4-oxadiazol-2-yl)
2-chloroethanethioate, tetra-tert-butylcalix[4]arene
1 | INTRODUCTION
possess structural features that are desirable for the
design and development of new drugs. These compounds
Antibiotic resistance is the ability of a microorganism to
stand the effect of an antibiotic. Thus the treatment of bac-
terial infections remains a challenging therapeutic prob-
lem, and to overcome the rapid development drug
resistance, new classes of antibacterial agents should pref-
erably have chemical characteristics that clearly differ
from those of existing agents. This has led to the design
and synthesis of many new antimicrobial agents.[1,2]
are easily synthesized and have variable conformations;
for instance, the calix[4]arenes can adopt several different
conformers, including the cone, partial cone, 1,2-alter-
nate, and 1,3-alternate. The calix[4]arenes can be
functionalized on the upper rim or on the lower rim with
several functional groups in a controlled manner. These
structural properties allow the use of these compounds in
supramolecular chemistry as scaffolds for the construc-
tion of various receptors, carriers, and spatial organizers.
Calix[4]arenes have been functionalized with different
pharmacophoric groups by many researchers and then
The calixarenes are a family of macrocyclic com-
pounds with a variable number of phenol units linked by
methylene bridges in the ortho position.[3] Calixarenes
© 2020 The Chemical Society Located in Taipei & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
J Chin Chem Soc. 2020;1–7.
http://www.jccs.wiley-vch.de
1

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DONO GEZELBASH AND AKBARI DILMAGHANI
evaluated for their biological activities such as anticancer,
antimicrobial, antiviral.[4–8]
Darmstadt, Germany), and A. fumigatus was cultured for
72 hr at 5ꢀC in Saburo Dextrose broth (Merck), and both
were used as inoculums.
Chemical modification of the phenolic oxygen at the
lower rim of tetra-tert-butylcalix[4]arene is easy and has
attracted significant attention due to the increased ability
of modified calixarenes to recognize ions, molecules, and
biomolecules. Recently, a review paper on the pharmaceu-
tical uses of calixarene derivatives has been published.[9]
1,3,4-Oxadiazole nucleus and its derivatives have
attracted much attention because of their pharma appli-
cations such as antimicrobials,[10] anticonvulsants,[11] as
well as anti-inflammatory,[12] antituberculostatic,[13]
fungicidal,[14] insecticidal,[15] and antioxidant[16] agents.
In particular, compounds bearing 1,3,4-oxadiazoles have
been successfully tested against several disease-causing
agents and therefore received special attention in biologi-
cal studies because of their diverse medicinal potentials.
In our previous works,[17–19] we reported the synthe-
sis and antibacterial properties of a new series of
thioglycoside heterocyclic derivatives of 1,2,4-triazole-
5-thiones and 1,3,4-oxadiazole-5-thiones.[20]
In the course of our search for new antimicrobial
agents with 1,3,4-oxadiazoles and 1,2,4-triazole moieties,
in this work we report the synthesis of some (5-aryl-1,-
3,4-oxadiazol-2-yl)2-chloroethanethioate derivatives (3a–
e) that are linked to calix[4]arene (1) at the lower rim.
We also evaluated the antimicrobial efficacy of these
oxadiazole derivatives (4a–e) against Escherichia coli and
Aspergillus fumigatus. The oxadiazole pharmacophores
(3a–e) incorporated into calix[4]arene are excellent bio-
isosteres of amides and esters and can contribute to
enhancing biological activity by participating in
hydrogen-bonding interactions. Coupling of the
oxadiazole pharmacophores to calix[4]arene causes syn-
ergy in the medicinal effects of these compounds.
1.3 | Susceptibility tests
The following methods were used to evaluate the activity
of the compounds. Minimum inhibition concentrations
(MIC) of the compounds against the tested pathological
microorganisms were determined using micro broth dilu-
tion method.[21] Briefly, each compound was dissolved in
dimethylsulfoxide (DMSO) and a solution with 500 μg/
mL concentration was prepared. Stock solutions were
added to MHB (BectonDickinson, Franklin Lakes, MD,
USA) at 40ꢀC and then poured into Petri plates to obtain
dilutions ranging from 7.8 to 100 μg/ml. Control micro-
titer plates containing the medium and distilled water at
similar dilutions were also prepared. Bacterial and fungal
suspensions were adjusted to 0.5 McFarland standards
(approximately 1–2 × 108 CFU/ml). A fixed amount of
the microorganisms was added to all the wells, and the
plate was incubated at 37 and 25ꢀC for 24–72 hr for E. coli
and A. fumigatus, respectively (final inoculate was
adjusted at 1.5 × 106 CFU per well). Each well was exam-
ined for growth by comparing it with the control. The
MIC was defined as the lowest concentration of the com-
pounds at which there was no visible growth of the organ-
isms. For each test, enrofloxacin and amphotericin were
used as the control antimicrobial agents. The minimum
bactericidal concentration (MBC; the lowest concentra-
tion of the compounds that resulted in a 99.9% reduction
in CFU of the initial inoculums) was determined by plat-
ing and counting the contents of wells that showed no vis-
ible growth of bacteria onto Mueller Hinton agar and
Saburo Dextrose agar plates and incubating at 37 and
25ꢀC for 24–72 hr for E. coli and A. fumigatus, respec-
tively. MBC was taken as as the lowest concentration of
the compounds that prevented any colony formation.
1.1 | Bacterial strain
The antibacterial and antifungal activities of the com-
pounds were assayed according to our perviously publi-
shed method.[21] The mentioned activities were tested
against E. coli and A. fumigatus.
1.4 | Statistical Analysis
All statistical analyses were performed by the SPSS 11.0
(SPSSFW, SPSS Inc, Chicago, IL) statistical package.
1.2 | Bacterial and fungi culture
The following microorganisms were used in this study to
test the antimicrobial activity of the compounds: E. coli
(PTCC 1399) and A. fumigatus (PTCC 5009). All microor-
ganisms were provided by the Persian Culture Collec-
tions of Microorganism, Iran. Bacteria were cultured for
24 hr at 37ꢀC in Brain heart infusion broth (Merck,
2 | RESULTS AND DISCUSSION
The main synthetic route for substituted 1,3,4-oxadiazole-
5-thiones (2a–e) involves an initial reaction between a
carboxylic acid hydrazide (1a–e) and carbon disulfide in
basic ethanol solution, followed by acidification with

DONO GEZELBASH AND AKBARI DILMAGHANI
3
SCHEME 1 Synthesis of S-(5-aryl-1,3,4-oxadiazol-2-yl)
2-chloroethanethioate derivatives
SCHEME 2 Synthesis of 5,11,17,23-tetra-tert-butyl-25,27-bis
S-(5-[aryl]-1,3,4-oxadiazol-2-yl) ethanethioate-26,28-dihydroxycalix
[4]arene derivatives
dilute hydrochloric acid, which results in the precipita-
tion of oxadiazole. These compounds were synthesized
according to the literature[22,23] (Scheme 1).
S-(5-Aryl-1,3,4-oxadiazole-2-yl)-2-chloroethaethioate
(3a–e) were prepared by the reaction of substituted
The observed MIC values listed in Table 2 indicate
that these compounds have higher antifungal effects in
comparison with enrofloxacin and amphotericin, which
are normally used for treating such infections. The best
results were obtained from 3c, 4c, and 4e, which showed
high activity against Aspergillus fumigates.
1,3,4-oxadiazole-5-thiones
(2a–e)
with
choloro
actylchloride. The reaction was carried out at 0–5ꢀC in
the presence of potassium carbonate in N,N-
dimethylformamide. The reaction mixture was stirred at
room temperature. After completion of the reaction, the
mixture was poured into cold water and the resulting
solid was filtered and crystalized to afford the pure title
products (3a–e) (Scheme 1).
Tetra-tert-butylcalix[4]arene (1) was prepared by the
Gutsche method as white crystals in good yield through
the one-step condensation of p-tert-butyl phenol with
formaldehyde and sodium hydroxide in diphenyl ether
under reflux condition.[3]
The synthesis of 5,11,17,23-tetra-tert-butyl-25,27-
bis-S-(5-[aryl]-1,3,4-oxadiazol-2-yl)ethanethioate-26,28-
dihydroxycalix[4]arene derivatives (4a–e) was carried out
by the reaction of tetra-tert-butylcalix[4]arene (1) with
S-(5-aryl-1,3,4-oxadiazole-2-yl)2-chloroethaethioate (3a–e)
in the presence of anhydrous K2CO3/KI in dry acetone
under reflux to give the expected products in moderate
yields (Scheme 2).
The in vitro antibacterial and antifungal activities of
the synthesized compounds in CH3Cl against E. coli and
A. fumigatus are presented in Tables 1 and 2. The mini-
mal inhibition concentration for enrofloxacin as refer-
ence antibacterial drug was 36 μg/μl and for
amphotericin 28 μg/μl under similar test conditions.
The observed MIC values in Table 1 indicate that
these compounds have higher antibacterial effects in
comparison with enrofloxacin and amphotericin, which
are normally used for treating such infections. The best
results were afforded by 3d, 3a, and 4e, which showed
high activity against E. coli. Preparation of the stock solu-
tions was in the range 10–100 μg/ml. In cases where MIC
and MBC were reported as negative (−), it means that
this compounds in this concentration range had no anti-
microbial activity.
3 | EXPERIMENTAL
3.1 | General
The melting points of all compounds were recorded on a
Philip Harris C4954718 apparatus without calibration.
FT-IR spectra were recorded on a Thermo Nicolet
670 Nexus spectrometer with KBr pellets. 1H NMR
(300 MHz) and 13C NMR (75 MHz) measurements were
carried out on a Bruker 300 MHz spectrometer in CDCl3
using TMS as the internal reference. ESI-MS measure-
ments were made on a Finnigan MAT 95 double-focusing
sector-field mass spectrometer. Thin-layer chromatogra-
phy (TLC) analyses were carried out on silica gel plates.
All chemicals were purchased from Merck (Tehran, Iran)
and used as received in all standard procedures. All appa-
ratuses, chemicals, and solvents were dried according to
standard methods. Freshly distilled solvents were used
throughout the experiments, and anhydrous solvents were
dried according to the method of Perrin and Armarego.[24]
Microanalyses were performed on a Leco Analyzer 932.
1HNMR, 13C NMR and FT-IR spectra of all products are
given in the supporting information section.
3.2 | Synthesis of tetra-tert-butylcalix[4]
arene (1)
It was prepared according to the Gutsche[25] method as
white crystals. Yield 3.97 g (62%), mp 340–343ꢀC; IR
(KBr) ν/cm−1: 3,158, 2,959, 2,905, 2,868, 2,744, 1,604,

4
DONO GEZELBASH AND AKBARI DILMAGHANI
TABLE 1 In vitro antibacterial activity of the synthesized compounds against E. coli
Compound
MIC (μg/μL)
MBC (μg/μL)
Compound
MIC (μg/μL)
MBC (μg/μL)
3a
3b
3c
3d
3e
10
15
—
10
—
20
30
—
10
—
4a
4b
4c
4d
4e
—
—
20
20
10
—
—
40
40
20
TABLE 2 In vitro antifungal activity of the synthesized compounds against A. fumigates
Compound
MIC (μg/μL)
MBC (μg/μL)
Compound
MIC (μg/μL)
MBC (μg/μL)
3a
3b
3c
3d
3e
—
—
10
—
20
—
—
20
—
40
4a
4b
4c
4d
4e
—
20
10
—
10
—
40
20
—
20
1
1,482, 1,201, 871, 817, 783, 743, 698; H NMR (300 MHz,
CDCl3) δH:1.22 (s, 36H, 4 × C[CH3]3), 3.5 (d, 4H,
J = 13.8 Hz, ArCH2Ar), 4.26 (d, 4H, J = 13.8 Hz,
ArCH2Ar), 7.06 (s, 8H, ArH), 10.34 (s, 4H, 4 × OH); 13C
NMR (75 MHz, CDCl3) δ (ppm):39, 32.60, 34.75, 125.93,
127.68, 144.36, 146.66.
room temperature. The formation of the titled intermediate
was confirmed by TLC using ethyl acetate/hexane as the
mobile phase. After completion of the reaction, the mixture
was poured into cold water and the product was collected.
3.2.3 | Synthesis of S-(5-phenyl-
1,3,4-oxadiazol-2-yl)
2-chloroethanethioate (3a)
3.2.1 | General procedure for the
synthesis of (2a–e)
Yield: 0.192 g, 75%, m.p. 160–162ꢀC; IR (KBr), υ/ cm−1
:
The main route for the synthesis of 5-substituted-1,-
3,4-oxadiazole-2-thiols/thiones (2a–e) involves an initial
reaction between an acylhydrazide (1a–e) (0.1 mol) and car-
bon disulfide 15.2 g (0.2 mol) in basic alcohol solution
(50 ml) followed by acidification of the reaction mixture. The
precipitate was filtered, washed thoroughly with cold water,
and recrystallized from ethanol to give 1,3,4-oxadiazole-
5-thiones (2a–e) (yield 60–70%). The following compounds
were prepared under analogous procedures.[22,23] Thiol–
thione tautomerism is known for the compounds 2a–e, and
one of the forms usually predominates.[26]
3,440, 2,930, 1,759, 1,622, 1,490, 1,316, 1,051, 968, 753,
1
689; H NMR (300 MHz, CDCl3) δ (ppm): 4.84 (2H, s,
CH2), 7.50–7.66 (3H, m, ArH), 7.94–8.02 (2H, m, ArH);
13C NMR (75 MHz, CDCl3) δ (ppm): 172.50, 162.67,
158.81, 133.43, 132.65, 130.33, 128.24, 127.50, 125.49,
43.44. Calcd: C, 47.16; H, 2.77; N, 11.00; S, 12.59%;
Found: C, 47.14; H, 2.75; N, 10.98; S, 12.58%.
3.2.4 | Synthesis of S-(5-[2-chlorophenyl]-
1,3,4-oxadiazol-2-yl)
2-chloroethanethioate (3b)
3.2.2 | General procedure for the
synthesis of S-(5-aryl-1,3,4-oxadiazole-2-yl)
2-chloroethanethioate (3a–e)
Yield: 0.22 g, 76%, m.p. 149–151ꢀC; IR (KBr), υ/ cm−1
:
3,444, 2,949, 1,764, 1,615, 1,591, 1,317, 1,032, 932, 729,
1
684; H NMR (300 MHz, CDCl3) δ (ppm): 4.84 (2H, s,
CH2), 7.44–7.50 (1H, m, ArH), 7.54–7.63 (2H, m, ArH),
7.95–7.97 (1H, d, J = 7.8 Hz, ArH); 13C NMR (75 MHz,
CDCl3) δ (ppm): 171.56, 162.63, 156. 60, 133.72, 132.90,
132.81, 132.00, 129.92, 128.48, 43.30. Calcd: C, 41.54; H,
2.09; N, 9.69; S, 11.09%; Found: C, 41.53; H, 2.07; N,
9.71; S, 11.08%.
1,3,4-Oxadiazole-5-thione (0.01 mol) was dissolved in N,N-
dimethylformamide (10 ml), to which potassium carbonate
(0.3–0.5 g) was added into the mixture and stirred for
30 min. Then chloroacetyl chloride (0.01 mol) was added
dropwise at 0–5ꢀC and the mixture was stirred for 3 hr at

DONO GEZELBASH AND AKBARI DILMAGHANI
5
3.2.5 | Synthesis of S-(5-[furan-2-yl]-
1,3,4-oxadiazol-2-yl)
2-chloroethanethioate (3c)
ethanethioate derivatives (400 mg, 1.81 mmol) were
refluxed in dried acetone (100 mL) for 80–90 hr. After
evaporation of the solvent, the residue was extracted with
dichloromethane. The organic layer was washed with
water, dried over magnesium sulfate, and evaporated in
vacuo. The residue was tritrated with methanol to give the
product mixture, which was recrystallized from MeOH.
Then the precipitate of the compound was submitted to
column chromatography (SiO2, EtOAc/hexane, 2:8).
Yield: 0.191 g, 79%, m.p. 105–108ꢀC; IR (KBr), υ/ cm−1:
3,145, 2,942, 1,769, 1,654, 1,466, 1,319, 1,251, 1,071,
1
945, 589; H NMR (300 MHz, CDCl3) δ (ppm): 4.80 (2H,
s, CH2), 6.67 (1H, s, furyl), 7.27 (1H, s, furyl), 7.73 (1H, s,
furyl); 13C NMR (75 MHz, CDCl3) δ (ppm): 171.25,
149.05, 146.39, 116.79, 113.97, 113.79, 43.35. Calcd: C,
39.28; H, 2.06; N, 11.45; S, 13.10%; Found: C, 39.27; H,
2.07; N, 11.43; S, 13.9%.
3.2.9 | Synthesis of 5,11,17,23-tetra-tert-
butyl-25,27-bis(S-(5-phenyl-1,3,4-oxadiazol-
2-yl)ethanethioate-26,28-dihydroxycalix[4]
arene (4a)
3.2.6 | Synthesis of S-(5-[2-nitrophenyl]-
1,3,4-oxadiazol-2-yl)
2-chloroethanethioate (3d)
Yield (0.23 g, 60%), m.p. 198ꢀC; IR (KBr), υ/ cm−1: 3,345,
3,406, 2,985, 1,745, 1,624, 1,479, 1,479, 1,123, 801, 569,
461; 1H NMR (300 MHz, CDCl3)δ (ppm): 1.22–1.52 (36H,
s, 4×C[CH3]3), 3.00 (1H, d, J = 15), 3.43–3.93 (3H, m),
3.98 (2H, s), 4.00–4.04 (3H, m), 4.29–4.43 (2H, m),
4.96–5.02 (1H, d, J = 18), 6.88 (4H, s, ArH), 7.00 (1H, s),
7.07 (2H, s), 7.29–7.34 (5H, m, ArH), 7.37–7.49 (5H, m,
ArH), 7.84–7.95 (5H, m, ArH); DEPT 135o (125 MHz,
CD2Cl2) δ (ppm): 29.33, 29.98, 30.71, 30.88, 31.07, 31.15,
31.17, 34.18, 37.63, 124.39, 125.53, 125.78, 125.85, 125.92,
125.99, 126.03, 127.51, 128.13, 128.36, 130.78, 130.99,
131.27; ESI-MS: m/z = 1,088.62 [M + H]; Calcd: C,
70.50; H, 6.39; N, 5.22; S, 5.97%; Found: C, 70.47; H,
6.33; N, 5.23; S, 5.85%.
Yield: 0.23 g, 76%, Lit: m.p. 119–121ꢀC; IR (KBr), υ/
cm−1: 3,440, 2,949, 1,771, 1,657, 1,536, 1,337, 1,304, 1,253,
1,042, 748, 720, 566; 1H NMR (300 MHz, CDCl3) δ (ppm):
4.77 (2H, s, CH2), 7.85–7.91 (3H, m, ArH), 8.14–8.17 (1H,
m, ArH); 13C NMR (75 MHz, CDCl3) δ (ppm): 171.68,
162.48, 159.19, 134.70, 133.08, 132.98, 132.71, 132.63,
132.53, 132.18, 43.30. Calcd: C, 40.08; H, 2.02; N, 14.02; S,
10.70%; Found: C, 40.07; H, 2.03; N, 14.01; S, 10.71%.
3.2.7 | Synthesis of S-(5-[3-nitrophenyl]-
1,3,4-oxadiazol-2-yl)
2-chloroethanethioate (3e)
Yield: 0.21 g, 74%, m.p. 134–138ꢀC; IR (KBr), υ/ cm−1:
3.2.10 | Synthesis of 5,11,17,23-tetra-tert-
butyl-25,27-bis S-(5-[2-chlorophenyl]-
1,3,4-oxadiazol-2-yl) ethanethioate-
26,28-dihydroxycalix[4]arene (4b)
3,332, 2,945, 2,875, 1,723, 1,537, 1,470, 1,354, 1,286, 1,196,
1
1,028, 718; H NMR (CDCl3, 300 MHz) δ(ppm): 4.77
(2H, s, CH2), 7.77 (1H, t, J = 7.8 Hz, ArH), 8.30 (1H, d,
J = 7.5 Hz, ArH), 8.45 (1H, d, J = 8.1, ArH), 8.82 (1H, s,
ArH); 13C NMR (75 MHz, CDCl3) δ (ppm): 178.23,
167.94, 162.94, 133.32, 133.26, 133.16, 124.94, 44.16.
Calcd: C, 40.08; H, 2.02; N, 14.02; S, 10.70%; Found:
40.06; H, 2.03; N, 14.00; S, 10.71%.
Yield (0.84 g, 62%), m.p. 178ꢀC; IR (KBr), υ/ cm−1: 3,410,
3,175, 2,927, 2,861, 1,711, 1,610, 1,669, 1,381, 1,276, 1,250,
1
1,186, 1,135, 1,186, 1,135, 1,040, 959, 899, 724, 600; H
NMR (300 MHz, CDCl3)δ (ppm): 1.28–1.53 (36H, m, 4×C
[CH3]3), 3.03 (1H, d, J = 12), 3.31–3.57 (3H, m), 4.00–4.03
(4H, m), 4.28–4.40 (2H, m), 4.29–4.43 (2H, m), 4.58 (1H,
s), 4.96–5.02 (1H, m), 6.85 (1H, s, ArH), 7.07–7.18 (4H, m,
ArH), 7.31 (2H, s), 7.37–7.51 (9H, m, ArH), 7.80–7.89
(2H, m, ArH); DEPT 135o (125 MHz, CD2Cl2) δ (ppm):
29.37, 29.94, 29.37, 29.94, 30.38, 30.41, 30.72, 30.94, 31.10,
31.15, 31.32, 33.72, 33.84, 34.18, 36.74, 37.65, 38.73,
124.40, 125.75, 125.82, 125.87, 125.95, 126.06, 126.22,
126.38, 127.45, 130.12, 130.28, 130.31, 130.35, 130.42,
130.55, 131.49; ESI-MS: m/z = 1,155.22 [M–H]; Calcd: C,
66.25; H, 5.82; N, 4.91; S, 5.61. Found: C, 66.15; H,
5.83; N, 4.85; S, 5.68.
3.2.8 | General procedure for the
synthesis of5,11,17,23-tetra-tert-butyl-
25,27-bis(S-(5-aryl-1,3,4-oxadiazol-2-yl)
ethanethioate-26,28dihydroxycalix[4]arene
5,11,17,23-Tetra-tert-butyl-25,27-bis-S-(5-[aryl]-1,3,4-oxa-
diazol-2-yl)ethanethioate-26,28-dihydroxycalix[4]arene
derivatives (4a–e). Calix[4]arene (571 mg, 0.724 mmol),
potassium carbonate (100 mg, 0.726 mmol), potassium
iodide (50 mg), and S-(5-aryl-1,3,4-oxadiazol-2-yl)2-chloro

6
DONO GEZELBASH AND AKBARI DILMAGHANI
3.2.11 | Synthesis of 5,11,17,23-tetra-tert-
butyl-25,27-bis S-(5-[furil]-1,3,4-oxadiazol-
2-yl)ethanethioate-26,28-dihydroxycalix[4]
arene (4c)
8, 124.19, 124.36, 125.91, 125.99, 126.11, 127.53, 130.85,
131.01, 131.83, 131.90, 132.48, 132.59, 132.68; ESI-MS: m/
z = 1,178.43 [M + H]; Calcd: C, 65.04; H, 5.72; N, 7.22; S,
5.51. Found: C, 65.00; H, 5.67; N, 7.25; S, 5.47.
Yield (0.2 g, 52%), m.p. 148ꢀC; IR (KBr), υ/ cm−1: 3,406,
3,166, 2,947, 1,712, 1,617, 1,475, 1,378, 1,290, 1,199, 1,121,
870, 741, 688; 1H NMR (300 MHz, CDCl3)δ (ppm):
0.9–1.41 (36H, m, 4×C[CH3]3), 3.36–3.53 (3H, m),
3.91–4.00 (5H, m), 4.21–4.36 (2H, m), 7.04–7.14 (7H, m),
7.36 (2H, m), 7.05–7.60 (5H, m); DEPT 135o (125 MHz,
CD2Cl2) δ (ppm): 29.00, 29.84, 30.69, 30.81, 30.93, 31.11,
37.49, 111.51, 113.05, 113.27, 113.80, 124.28, 125.60,
125.78, 125.83, 125.94, 126.02, 127.43, 145.26; ESI-MS: m/
z = 1,066.48 [M–H]; Calcd: C, 67.28; H, 6.12; N, 5.32; S,
6.09. Found: C, 67.18; H, 6.10; N, 5.35; S, 6.00.
4 | CONCLUSIONS
A series of new tetra-tert-butyl calix[4]arene derivatives
(4a–e) were prepared by the reaction of S-(5-aryl-1,-
3,4-oxadiazol-2-yl)2-chloroethanethioate moieties (3a–e)
with calix[4]arene (1) in the presence of potassium car-
bonate. The antimicrobial results obtained from novel
calix[4]arene derivatives (4a–e) revealed that among the
synthesized compounds, 4c was most effective against
A. fumigates. Compound 4e was found to be most effec-
tive against E. coli and A. fumigates.
3.2.12 | Synthesis of 5,11,17,23-tetra-tert-
butyl-25,27-bis S-(5-[2-nitrophenyl]-
1,3,4-oxadiazol-2-yl) ethanethioate-
26,28-dihydroxycalix[4]arene (4d)
ACKNOWLEDGMENTS
We thank Prof. Dr. Joachim Thiem, Hamburg University,
for the ESI-MS measurements. We are grateful to Urmia
University for providing fellowships for carrying out the
present work.
Yield (0.19 g, 65%), m.p. 188ꢀC; IR (KBr), υ/ cm−1: 3,451,
2,956, 1,759, 1,538, 1,475, 1,356, 1,297, 1,189, 1,132,
876, 723, 563; 1H NMR (300 MHz, CDCl3)δ (ppm):
1.22–1.41 (36H, m, 4×C[CH3]3), 3.50 (1H, d, J = 12),
3.33–3.69 (3H, m), 3.98–4.04 (5H, m), 4.18–4.23 (2H, m),
4.52 (1H, s), 7.07(2H, s), 7.15 (1H, s), 7.27 (1H, s),
7.43–7.49 (2H, m, ArH), 7.69–7.2 (6H, m), 7.82–7.86 (2H,
m, ArH), 7.88–8.01 (3H, m, ArH); DEPT 135o (125 MHz,
CD2Cl2) δ (ppm): 30.55, 30.61, 30.74, 33.79, 124.14, 124.74,
124.79, 124.89, 125.06, 125.53, 125.73, 126.03, 126.13,
131.02, 131.25, 131.79, 131.91, 132.47, 132.51, 132.64; ESI-
MS: m/z = 1,178.48 [M + H]; Calcd: C, 65.04; H, 5.72; N,
7.22; S, 5.51. Found: C, 65.00; H, 5.64; N, 7.25; S, 5.44.
ORCID
Zahra Dono Gezelbash https://orcid.org/0000-0001-
5976-2083
Karim Akbari Dilmaghani https://orcid.org/0000-0002-
0084-3580
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
How to cite this article: Dono Gezelbash Z,
Akbari Dilmaghani K. Synthesis, antifungal and
antibacterial activity of calix[4]arene-based 1,3,4-
oxadiazole derivatives. J Chin Chem Soc. 2020;1–7.
https://doi.org/10.1002/jccs.201900425