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Acta Chim. Slov. 2016, 63, 790-797
DOI: 10.17344/acsi.2016.2637
Scientific paper
Synthesis of a Series of Novel Tetra-tert-butylcalix[4]arene Linked to 1,2,4-Triazole and 1,3,4-Oxadiazole Derivatives
Zahra Dono Ghezelbash and Karim Akbari Dilmaghani*
Department of Organic Chemistry, Faculty of Chemistry, Urmia University, Urmia, 57159, Iran
* Corresponding author: E-mail: k.adilmaghani@urmia.ac.ir Tel: (+98)914-443-1392; Fax: (+98)44-357153-165
Received: 29-05-2016
Abstract
A series of tetra-tert-butylcalix[4]arene linked to 1,2,4-triazole-5-thiones and 1,3,4-oxadiazole-5-thiones derivatives at lower rim were synthesized by the reaction of 1,2,4-triazole-5-thione and 1,3,4-oxadiazole-5-thione with 5,11,17,23-te-tra-terf-butyl-25,27-bis(3-bromopropoxy)-26,28-dihydroxycalix[4]arene (2). The synthesized compounds were characterized by FT-IR, 1H NMR, 13C NMR spectral data, elemental analysis and ESI-MS.
Keywords: Tetra-tert-butylcalix[4]arene, 1,2,4-triazole-5-thione, 1,3,4-oxadiazole-5-thione, macrocycle
1. Introduction
During the last three decades, due to the rapid development of drug resistance, numerous searches for new bi-oactive compounds have been conducted through screening and synthesizing new compounds with chemical characteristics clearly different from those of existing agents. Calixarene derivatives not only have been used in macro-molecular chemistry, catalysis and separation techniques but they also have attracted much interest for their potential use in drug design and delivery.1-7 Their controlled functionalization has allowed the use of these compounds in supramolecular chemistry as scaffolds for the construction of various receptors, carriers, and spatial organizers. Calix[4]arenes have been investigated for their biological proprieties; for example hydrophilic derivatives have shown interesting levels of activity against bacteria, cancerous cell, fungi, enveloped virus thrombosis, and fibro-sis diseases.8-14
1,2,4-Triazole-5-thiones and 1,3,4-oxadiazole-5-thiones scaffolds are heterocyclic compounds containing five membered rings and their derivatives have been studied due to their diverse pharmacological proprieties, such as antibacterial and antifungal,15-22 antimicrobial,23-25 anti-inflammatory,22,26 and antiviral activities.27,28 Calix[4]arenes represent a third generation of su-pramolecular hosts after cyclodextrins and crown ethers,
with unique three-dimensional structures. Tetra-tert-butylcalix[4]arene (1) was prepared by Gutsche 29 method as white crystals in good yield through a one-step condensation of p-tert-butyl phenol with formaldehyde and sodium hydroxide in diphenyl ether under reflux condition. Calix[4]arenes can be selectively functionalized at either narrow rim if the derivatization of calix[4]arenes occurs at the phenolic oxygen or wide rim if it occurs at the para position after the removal of para-tert-butyl groups. Recently, a review paper on the pharmaceutical uses of calixarene derivatives has been published.30
In our previous works,31-33 we reported the synthesis and antibacterial properties with new series of thioglyco-side heterocyclic derivatives of 1,2,4-triazole-5-thiones and 1,3,4-oxadiazole-5-thiones. Here we report the synthesis of novel tetra-tert-butylcalix[4]arene derivatives containing a series of 1,2,4-triazole-5-thione and 1,3,4-oxadiazole-5-thione moieties at the lower rim; we expected that antibacterial properties of these compounds 4a-e and 6f-k will be of interest.
2. Result and Discussion
1-Substituted-4-phenylthiosemicarbazides 2a-e were prepared by the condensation of carboxylic acid hydra-zides 1a-k with phenylisothiocyanate under reflux in ab-
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solute ethanol. The cyclodehydration of 1-substituted-4-phenylthiosemicarbazides 2a-e were carried out in alkaline medium followed by acidification with dilute hydrochloric acid to give 1,2,4-triazole-5-thiones 3a-e according to the literature34-36 (Scheme 1).
The main synthetic route for substituted 1,3,4-oxa-diazole-5-thiones 5f-k involves an initial reaction between carboxylic acid hydrazides 1a-k and carbon disulfide in basic ethanol solution, followed by acidification with dilute hydrochloric acid which results in the precipitation of oxadiazole. These compounds were synthesized according to the literature method37,38 (Scheme 1).
The synthesis of 5,11,17,23-tetra-tert-butyl-25,27-bis(3-bromopropoxy)-26,28-dihydroxycalix[4]arene (2) was carried out by the reaction of tetra-tert-butylca-lix[4]arene (1) with 1,3-dibromo propane and K2CO3 in acetonitrile according to the procedure reported in the lite-rature39 (Scheme 2).
The existence of thiol-thione tautomerism is known for the compounds 3a-e and 5f-k and generally one forms is predominant.40-43 Replacement of the bromine of compound 2 with 1,2,4-triazole-5-thiones 3a-e or 1,3,4-oxadiazole-5-thiones 5f-k was carried out in aqueous alkaline media in dimethylformamide to afford the corres-
ponding coupled calix[4]arenes, i.e. compounds 4a-e and 6f-k, respectively (Scheme 3).
An important property of calixarenes is that the aromatic rings can rotate and produce different conformations (cone, partial cone, 1,3-alternate and 1,2-alter-nate). The cone conformation is the most favored among the four conformations due to the very strong intramolecular hydrogen bonding between four OH groups at the lower rim of the unsubstituted calix[4]arene. The conformation of a specific calix[4]arene sample can be easily distinguished by its characteristic :H-NMR patterns arising from the ArCH2Ar methylene protons.44-47 Cone conformation is a preferred conformation which corresponds to the minimum energy. The cone conformer is identified by one characteristic pair of doublets of the Ar-CH2-Ar methylene protons (AB system, a coupling constant 2 J = 12-15 Hz is characteristic for geminal protons). The 1H-NMR spectra indicating that 4a-e and 6f-k exist in the cone conformation. Different factors such as the size of the functional groups attached, interactions between the groups, and temperature, among others, influence the rings to either freely rotate or become fixed in a conformation. We suppose that two factors might influence for this conformation selectivity. Firstly,
Scheme 1. Synthesis of 1,2,4-triazole-5-thione and 1,3,4-oxadiazole-5-thione derivatives.
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Acta Chim. Slov. 2016, 63, 790-797	DOI: 10.17344/acsi.2016.2637
Scheme 3. Synthesis of 1,2,4-triazole-5-thiones and 1,3,4-oxadiazole-5-thiones linked to tetra-ieri-butyl calix[4] arene.
the conformation changes of calix[4]arene (2) controlled by regulating the temperature and secondly the derivati-zation of calix[4]arenes with bulky groups at phenolic oxygen atoms usually leads to conformationally rigid compounds.
The conformations of calix[4]arene can be deduced from the 13C-NMR chemical shifts of the methylene groups connecting each pair of aromatic rings.48 The structures of the new compounds were fully confirmed by their FT-IR, 1H-NMR, 13C-NMR, DEPT, and mass spectra (ESI-MS).
3. Experimental
3. 1. General
The melting points of all compounds were recorded on a Philip Harris C4954718 apparatus without calibration. IR and 1H- and 13C-NMR spectra were recorded on Thermo Nicolet Nexus 670 FT-IR and Bruker Avance 300 MHz spectrometers, respectively. ESI-MS measurements were recorded on a Finnigan MAT 95 double-focusing sector-field mass spectrometer. Thin layer chromato-graphy (TLC) analyses were carried out on silica gel pla-
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tes. All chemicals were purchased from Merck (Tehran, Iran) and used as received by standard procedures. All of the instruments, chemicals and solvents were dried according to standard methods. Freshly distilled solvents were used throughout, and anhydrous solvents were dried according to the method reported by Perrin and Armarego.49 Microanalyses were performed on a Leco Analyzer 932.
3. 2. General Procedure for the Synthesis of 3a-e:
Equimolar quantities of carboxylic acid hydrazides 1a-k (0.01 mol) and phenyl isothiocyanate (1.35 g, 0.01 mol) in appropriate amount of absolute ethanol were ref-luxed for 6-8 h. The formed precipitate of 1-substituted-4-phenylthiosemicarbazides was filtered, and then a suspension of 0.04 g thiosemicarbazides in sodium hydroxide 0.4 g (0.01 mol, as a 2N solution) was refluxed for 6 h. The reaction mixture was allowed to cool to the room temperature and was then adjusted to pH 6 with diluted hydrochloric acid. The formed precipitate was then filtered, washed with water, dried and recrystallized from et-hanol to give 1,2,4-triazole-5-thiones 3a-e in 65-75% yields. The following compounds were prepared by an analogous procedure.34-36
General Procedure for the Synthesis of 5f-k:
Into a stirred solution of carboxylic acid hydrazides 1a-k (0.1 mol) and KOH (5.61 g, 0.1 mol) in absolute ethanol (50 mL), CS2 (15.2 g, 0.2 mol) was added and the mixture was refluxed for 6 h, until the evolution of hydrogen sulfide has ceased. The reaction mixture was cooled to the room temperature and diluted with water. On acidification with dilute hydrochloric acid, the desired oxadiazole was precipitated. The precipitate was filtered, washed thoroughly with cold water and recrystallized from ethanol to give 1,3,4-oxadiazole-5-thiones 5f-k in 65-70% yields. The following compounds were prepared by an analogous
procedure.37-38
Synthesis of Tetra-tert-butylcalix[4]arene (1):
It was prepared by Gutsche method29 as white crystals. Yield 3.97g (62%), mp 340-343 °C; IR (KBr) v /cm-1 : 3158, 2959, 2905, 2868, 2744, 1604, 1482, 1201, 871, 817, 783, 743, 698; 1H NMR (300 MHz, CDCl3): 5H 1.22 (s, 36H, 4 x 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 x OH); 13C NMR (300 MHz,
CDCl3): 5c 31.39, 32.60, 34.75, 125.93, 127.68, 144.36, 146.663 . c
Synthesis of 5,11,17,23-Tetra-tert-butyl-25,27-bis (3-bromopropoxy)-26,28-dihydroxycalix[4]arene (2):
It was also prepared with a cone conformation according to the literature procedure.39 White crystals, 1.06 g (77%), mp 288-290 °C; IR (KBr) v/cm-1 : 3406, 3044, 2959,
2904, 2867, 1598, 1485, 1201, 1023, 872; 1H NMR (300 MHz, CDCl3): 5H 1.03 (s, 18H, 2 x C(CH3)3), 1.29 (s, 18H, 2 x C(CH3)3), 2.54 (t, 4H, J = 5.7 Hz, 2 x CH2), 3.36 (d, 4H, J = 12.9 Hz, ArCH2Ar), 4.02 (t, 4H, J = 6.6 Hz, 2 x CH2Br), 4.13 (t, 4H, J = 5.4 Hz, 2 x OCH2), 4.28 (d, 4H, J = 12.9 Hz, ArCH2Ar), 6.89 (s, 4H, ArH), 7.06 (s, 4H, ArH), 7.66 (s, 2H, 2 x OH); 13C NMR (300 MHz, CDCl3): 5c 30.36, 31.05, 31.69, 31.88, 33.51, 33.82, 34.04, 73.35, 125.21, 126.71, 127.54, 132.79, 141.69, 147.27, 149.17, 150.59.
General Procedure for the Synthesis of Tetra-tert-butylcalix[4]arene Derivatives 4a-e and 6f-k:
1,2,4-Triazole or 1,3,4-oxadiazole derivatives (1 mmol) 3a-e or 5f-k was added to a solution of 0.04g (1 mmol) NaOH in H2O (0.5 mL) and DMF (35 mL). The mixture was stirred at room temperature for 30 min, 0.223 g (0.25 mmol) of compound 2 was added and stirring at room temperature was continued for further 15 h. The reaction mixture was transferred into cool water and the precipitate was filtered and then recrystallized from methanol, then the precipitate of the compound was submitted to column chromatography (SiO2, EtOAc/hexane, 3:8).
Synthesis of 5,11,17,23-Tetra-tert-butyl-25,27-bis(4,5-diphenyl-1,2,4-triazole-3-thiapropoxy)-26,28-dihy-droxycalix[4]arene (4a):
White crystals; 40% (0.143 g), mp 160-162 °C; IR (KBr) v/cm-1: 3424, 2936, 1575, 1420, 1204, 1052, 763, 694, 639; 1H NMR (300 MHz, CDCl3): 5H 1.03 (s, 18H, 2 x C(CH3)3), 1.29 (s, 18H, 2 x C(CH3)3), 2.56 (m, 4H, 2 x CH2), 3.31 (d, 4H, J = 12.6 Hz, ArCH2Ar), 3.79 (m, 4H, 2 x SCH2), 4.12 (m, 4H, 2 x OCH2), 4.24 (d, 4H, J = 12.8 Hz, Ar2CH2Ar), 6.88 (s, 4H, Ar2H), 7.05 (s, 4H, ArH), 7.24-7.27 (m, 10H, ArH), 7.41-7.47 (m, 10H, ArH), 7.78 (s, 2H, 2 x OH); 13C NMR (300 MHz, CDCl3): 5c 29.67, 30.16, 31.37, 31.77, 32.40, 74.34, 125.92, 125.97, 126.42, 126.45, 127.87, 128.54, 128.78, 129.89, 147.18, 149.36, 150.67, 152.67, 152.77, 154.87; DEPT 135o (125 MHz, CD2Cl2) 5 (ppm): 130.25, 130.12, 129.89, 128.78, 128.53, 127.86, 126.44, 125.91, 74.35, 32.44, 31.72, 31.32, 30.15, 29.65; ESI-MS: m/z = 1235.62 [M+H], Calcd: C, 75.35; H, 6.67; N, 7.12; S, 5.44%. Found: C, 75.29; H, 6.61; N, 7.17; S, 5.33%.
Synthesis of 5,11,17,23-Tetra-tert-butyl-25,27-bis(5-(4-hydroxyphenyl)-4-phenyl-1,2,4-triazol-3-thiapro-poxy)-26,28-dihydroxycalix[4]arene (4b):
White crystals; 46% (0.151 g), mp 185-187 °C; IR (KBr) v/cm-1: 3409, 3048, 2952, 1599, 1554, 1477, 1305, 1208, 1020, 925, 878, 752, 693, 630, 557; 1H NMR (300 MHz, CDCl3): 5h 1.04 (s, 18H, 2 x C(CH3)3), 1.31 (s, 18H, 2 x C(CH3)3), 2.49 (m, 4H, 2 x CH2), 3.33 (d, 4H, J = 12.9 Hz, ArCH2Ar), 3.61 (m, 4H, 2 x SCH2), 4.08 (m, 4H, 2 x OCH2), 4.23 (d, 4H, J = 12.6 Hz, ArCH2Ar), 6.88 (s, 4H, ArH), 6.97 (t, 2H, J = 7.2 Hz, ArH), 7.06 (s, 4H, ArH),
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7.24 (s, 2H, 2 x OH) 7.26 (t, 2H, J = 7.5 Hz, ArH), 7.36 (d, 4H, J = 7.2 Hz, ArH), 7.49-7.56 (m, 10H, ArH + 2 x OH), 7.74(s, 2H, 2 x OH); 13C NMR (300 MHz, CDCl3): 5 29.98, 30.23, 31.36, 31.72, 32.44, 73.38, 117.43,
c	'	'	'	'	'	'	'
117.49, 122.01, 125.47, 125.96, 128.09, 130.45, 130.64, 130.88, 147.09, 149.43, 150.65, 151.51; DEPT 135o (125 MHz, CD2Cl2) 5 (ppm): 130.85, 130.66, 130.40, 128.04, 126.43, 125.91, 122.03, 117.48, 117.42, 74.32, 32.44, 31.73, 31.34, 30.23, 30.00; ESI-MS: m/z = 1265.65 [M-H]; Calcd: C, 73.36; H, 6.49; N, 6.94; S, 5.29 %. Found: C, 73.19; H, 6.53; N, 6.83; S, 5.24%.
Synthesis of 5,11,17,23-Tetra-ieri-butyl-25,27-bis(5-(2-chlorophenyl)-4-phenyl-1,2,4-triazole-3-thiapro-poxy)-26,28-dihydroxycalix[4]arene (4c):
White crystals; 0.14 g (40%), mp 250-252 °C; IR (KBr) v/cm-1: 3432, 3033, 2956, 1595, 1485, 1430, 1301, 1200, 1123, 1031, 873, 763, 964, 600; 1H NMR (300 MHz, CDCl3): 5h 1.02 (s, 18H, 2 x C(CH3)3), 1.34 (s, 18H, 2 x C(CH3)3), 2.59 (m, 4H, 2 x CH2), 3.29 (d, 4H, J = 12.9 Hz, ArCH2Ar), 3.85 (m, 4H, 2 x SCH2), 4.12 (m, 4H, 2 x OCH2), 4.2 (d, 4H, J = 12.6 Hz, ArCH2Ar), 6.85 (s, 4H, ArH), 7.04 (s, 4H, ArH), 7.14-7.15 (m, 4H, ArH), 7.27-7.41 (m, 14H, ArH), 7.73 (s, 2H, 2 x OH); 13C NMR (300 MHz, CDCl3): 5c 29.65, 31.01, 31.12, 31.68, 31.72, 33.81, 73.32, 125.09, 125.69, 126.70, 126.87, 127.49, 129.52, 129.92, 132.75, 133.37, 141.49, 147.06, 149.39, 150.71, 152.27, 153.28; DEPT 135o (125 MHz, CD2Cl2): 5 147.05, 141.49, 133.37, 132.74, 129.91, 129.53, 127.41, 126.88, 125.69, 125.06, 73.32, 33.83, 31.63, 31.14, 31.03, 29.67; ESI-MS: m/z = 1305.46 [M+H]; Calcd: C, 71.19; H, 6.14; N, 6.73; S, 5.14%. Found: C, 70.85; H, 6.07; N, 6.79; S, 5.10%.
Synthesis of 5,11,17,23-Tetra-ieri-butyl-25,27-bis(5-(2-hydroxy phenyl)-4-phenyl-1,2,4-triazol-3-thiapro-poxy)-26,28-dihydroxycalix[4]arene (4d):
White crystals; 0.14 g (0.43%), mp 190-192 °C; IR (KB-r) v/cm-1: 3352, 3051, 2952, 1589, 1481, 1293, 1247, 1204, 1023, 747, 699, 609; 1H NMR (300 MHz, CDCl3): 5h 1.04 (s, 18H, 2 x C(CH3)3), 1.29 (s, 18H, 2 x C(CH3)3), 2.53 (m, 4H, 2 x CH2), 3.31 (d, 4H, J = 12.9 Hz, Ar-CH2Ar), 3.64-3.80 (m, 4H, 2 x SCH2), 4.09 (m, 4H, OCH2), 4.19 (d, 4H, J = 12.6 Hz, ArCH2Ar), 6.51-6.57 (m, 2H,ArH), 6.88 (s, 4H, ArH), 7.04 (s, 4H, ArH), 7.09 (s, 2H, 2 x OH), 7.17-7.36 (m, 8H, ArH), 7.49-7.58 (m, 8H, ArH), 7.77 (s, 2H, 2 x OH); 13C NMR (300 MHz, CDCl3): 5c 29.66, 30.03, 30.07, 30.29, 31.32, 31.72, 32.42, 74.19, 74.45, 117.43, 117.91, 118.81, 122.04, 125.90, 125.95, 126.04, 126.45, 126.94, 128.09, 128.17, 129.39, 130.71, 130.85, 131.03, 131.54, 146.49, 149.38, 151.38, 153.30; DEPT 135o (125 MHz, CD2Cl2): 5 131.00, 130.90, 130.83, 130.71, 129.39, 128.14, 128.02, 126.45, 126.04, 125.94, 125.90, 122.04, 118.82, 117.98, 117.43, 74.45, 74.18, 32.42, 31.72, 31.33, 30.29, 30.07, 30.00, 29.67; ESI-MS: m/z = 1266.63 [M-H]; Calcd: C,
73.36; H, 6.49; N, 6.94; S, 5.29%. Found: C, 73.25; H, 6.54; N, 6.90; S, 5.31%.
Synthesis of compound : 5,11,17,23-Tetra-feri-butyl-
25.27-bis(5-(furan-2-yl)-4-phenyl-1,2,4-triazole	3-thia-propoxy)-26,28-dihydroxycalix[4]arene (4e):
White crystals; 0.113 g (43%), mp 195-197 °C; IR (KBr) v/cm-1: 3382, 2936, 2870, 1600, 1477, 1204, 1021, 725, 696, 604; 1H NMR (300 MHz, CDCl3): 5H 1.01 (s, 18H, 2 x C(CH3)3), 1.27 (s, 18H, 2 x C(CH3)3), 2.49 (m, 4H, 2 x CH2), 3.28 (d, 4H, J = 13 Hz, ArCH2Ar), 3.78 (t, 4H, J = 6.6 Hz, 2 x SCH2), 4.07 (t, 4H, J = 5.4 Hz, 2 x OCH2), 4.1 (d, 4H, J = 15.6 Hz, ArCH2Ar), 6.15 (d, 2H, J = 3.39 Hz, H furyl), 6.32 (t, 2H, J = 1.8 Hz, H furyl), 6.85 (s, 4H, ArH), 7.02 (s, 4H, ArH), 7.27-7.31 (m, 3H, ArH), 7.4 (d, 2H, H furyl), 7.53-7.55 (m, 7H, ArH), 7.69 (s, 2H, 2 x OH); 13C NMR (300 MHz, CD2Cl2): 5c 29.33, 29.80, 31.68, 31.92, 32.16, 33.99, 73.74, 111.15, 125.11, 125.60, 127.54, 129.95, 130.35, 132.72, 133.67, 141.52, 141.61, 143.81, 143.94, 147.07, 147.91, 149.37, 151.61; DEPT 135o (125 MHz, CDCl3): 5 133.68, 132.73, 130.37, 129.95, 127.54, 125.61, 125.11, 111.15, 73.74, 33.98, 32.16, 31.92, 31.67, 29.81, 29.33; ESI-MS: m/z = 1232.71 [M+H]; Calcd: C, 72.51; H, 6.43; N, 7.25, S, 5.53%. Found: C, 75.40; H, 6.39; N, 7.21; S, 5.43%.
Synthesis of 5,11,17,23-Tetra-tert-butyl-25,27-bis (5-(phenyl)-1,3,4-oxadiazole-2-thiapropoxy)-26,28-dihydroxycalix[4]arene (6f):
White crystals; 0.145 g (53%), mp 150-152 °C; IR (KBr) v/cm-1: 3386, 2951, 1599, 1474, 1197, 1037, 879, 696, 473; 1H NMR (300 MHz, CDCl3): 5H 1.01 (s, 18H, 2C(CH3)3), 1.29 (s, 18H, 2C(CH3)3), 2.60 (m, 4H, 2CH2), 3.37 (d, 4H, J = 12.9 Hz, ArCH2Ar), 3.91 (m, 4H, 2SCH2), 4.18 (m, 4H, 2 x OCH2), 4.27 (d, 4H, J = 12.6 Hz, A2rCH2Ar), 6.87 (s, 4H, Ar2H), 7.07 (s, 4H, ArH), 7.45-7.50 2(m, 6H, ArH), 7.63 (s, 2H, 2OH), 7.88-8.00 (m, 4H, ArH); 13C NMR (300 MHz, CDCl3): 5c 29.63, 29.93, 30.43, 30.73, 31.15, 31.27, 32.37, 32.42, 33.83,
53.23,	53.32, 73.35, 73.55, 125.55, 125.78, 126.09, 126.42, 127.57, 129.58, 130.53, 132.21, 132.72, 141.77, 149.18, 150.60; DEPT 135o (125 MHz, CD2Cl2): 5132.72, 132.22, 130.54, 129.53, 127.55, 126.47, 126.05, 125.78, 125.52, 73.55, 73.35, 53.33, 53.35, 33.87, 32.43, 32.33,
31.24,	31.19, 30.77, 30.43, 29.45, 29.66; ESI-MS: m/z = 1084.48 [M-H]; Calcd: C, 72.34; H, 6.66; N, 5.44; S, 6.23%. Found: C, 72.19; H, 6.57; N, 7.40; S, 6.30%.
Synthesis of 5,11,17,23-Tetra-tert-butyl-25,27-bis(5-(2-chlorophenyl)-1,3,4-oxadiazole-2-thiapropoxy)-
26.28-dihydroxycalix[4]arene	(6g):
White crystals; 0.136 g (48%), mp 218-220 °C; IR (KBr) v/cm-1: 3355, 2949, 1597, 1470, 1293, 1191, 1095, 1031, 884, 731, 649; 1H NMR (300 MHz, CDCl3): 5H 1.01 (s, 18H, 2C(CH3)3), 1.29 (s, 18H, 2C(CH3)3), 2.61 (m, 4H, 2CH2), 3.37 (d, 4H, J = 13.2 Hz, ArCH2Ar),
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3.91-3.93 (m, 4H, 2SCH2), 4.18 (m, 4H, 2OCH2), 4.26 (d, 4H, J = 12.6 Hz, ArCH2Ar), 6.88 (s, 4H, ArH), 7.07 (s, 4H, ArH), 7.34-7.42 (m, 4H, ArH), 7.50 (d, 2H, ArH), 7.66 (s, 2H, 2OH), 7.91(d, 2H, ArH); 13C NMR (300 MHz, CDCl3): 5c 29.71, 29.78, 30.65, 30.88, 30.95, 31.16, 31.61, 32.08, 33.89, 53.48, 53.85, 73.33, 73.45,
125.78,	125.85, 126.06, 126.22, 126.55, 130.31, 131.55, 132.65, 141.77, 147.29, 149.19, 150.54; DEPT 135o (125 MHz, CD2Cl2): 5 132.67, 131.54, 130.33, 126.57, 126.25, 126.08, 125.80, 125.75, 73.46, 73.35, 53.87, 53.43, 33.83, 32.04, 31.69, 31.17, 30.93, 30.85, 30.66, 29.80, 29.70; ESI-MS: m/z = 1138.33 [M-H]; Calcd: C, 67.81; H, 6.06; N, 5.10; S, 5.84%. Found: C, 67.69; H, 5.95; N, 5.14; S, 5.78%.
Synthesis of 5,11,17,23-Tetra-feri-butyl-25,27-bis(5-(2-hydroxy phenyl)-1,3,4-oxadiazole-2-thiapropoxy)-26,28-dihydroxycalix[4]arene (6h):
White crystals; 0.138 g (49%), mp 240-242 °C; IR (KBr) v/cm-1: 3393, 2951, 1743, 1595, 1476, 1295, 1202, 1112, 1024, 911, 734, 637, 566; 1H NMR (300 MHz, CDCl3): 5H 1.04 (s, 18H, 2C(CH3)3), 1.29 (s, 18H, 2C(CH3)3), 2.54-2.61 (m, 4H, 2CH2), 3.37 (d, 4H, J = 12.6 Hz, ArCH2Ar), 3.93-4.13 (m, 4H, 2SCH2), 4.18-4.26 (m, 4H, 2OCH2), 4.28 (d, 4H, J = 12.9 Hz, ArCH2Ar), 6.88-6.93 (m, 7H, ArH), 6.93-7.07 (m, 7H, ArH), 7.41 (s, 2H, 2 x OH), 7.87-7.93 (m, 4H, 2OH + ArH); 13C NMR (300 MHz, CDCl3): 5c 29.51, 29.61, 30.83, 30.95, 30.99, 31.38, 31.97, 32.09° 33.59, 53.44, 53.64, 53.80, 73.53, 73.66, 117.24, 119.65, 125.58,
125.67,	126.15, 126.19, 126.51, 133.49, 147.38, 149.12, 150.48, 157.13, 165.22; DEPT 135o (125 MHz, CD2Cl2): 5 133.47, 126.43, 126.17, 126.14, 125.63, 125.60, 119.94, 117.20, 73.64, 73.56, 53.80, 53.61, 53.43, 33.53, 32.04, 31.99, 31.32, 30.93, 30.65, 30.81, 29.50, 29.64; ESI-MS: m/z =1116.51 [M-H]; Calcd: C, 70.16; H, 6.46; N, 5.28; S, 6.04%. Found: C, 69.99; H, 6.40; N, 5.17; S, 6.10%.
Synthesis of 5,11,17,23-Tetra-feri-butyl-25,27-bis (5-(furan-2-yl)-1,3,4-oxadiazole-2-thiapropoxy)-26,28-dihydroxycalix[4]arene (6i):
White crystals; 0.161 g (60%), mp 140-142 °C; IR (KBr) v/cm-1: 3418, 2951, 1629, 1472, 1195, 1091, 894, 754, 468; 1H NMR (300 MHz, CDCl3): 5H 0.99 (s, 18H, 2C(CH3)3), 1.32 (s, 18H,2 x C(CH3)3), 2.61 (m, 4H, 2CH2), 3.39 (d, 4H, J = 12.9 Hz, ArCH2Ar), 3.92 (m, 4H, 2SCH2), 4.19 (m, 4H, 2OCH2), 4.28 (d, 4H, J = 12.9 Hz, ArCH2Ar), 6.28 (m, 2H, H furyl), 6.88 (s, 4H, ArH), 6.92 (d, 2H, J = 3.3 Hz, H furyl), 7.10 (s, 4H, ArH), 7.37 (s, 2H, H furyl), 7.80 (s, 2H, 2OH); 13C NMR (300 MHz, CDCl3): 5c 29.55, 29.59, 29.65, 29.68, 30.91, 30.94, 31.35, 31.38, 32.04, 32.07, 53.64, 53.67, 73.79, 112.13,
113.79,	125.43, 125.66, 126.11, 145.65, 147.36, 149.16, 158.59, 163.65; DEPT 135o (125 MHz, CD2Cl2): 5
145.68,	126.15, 125.60, 113.74, 112.04, 73.64, 53.79,
53.61, 32.06, 32.03, 31.35, 31.33, 30.95, 30.93, 29.68, 29.66, 29.56, 29.54; ESI-MS: m/z = 1066.48 [M+H]; Calcd: C, 69.02; H, 6.39; N, 5.55; S, 6.35%. Found: C, 68.85; H, 6.37; N, 5.27; S, 6.30%.
Synthesis of 5,11,17,23-Tetra-ieri-butyl-25,27-bis(5-(2-nitrophenyl)-1,3,4-oxadiazole-2-thiapropoxy)-26,28-dihydroxycalix[4]arene (6j):
White crystals; 0.140 g (47%), mp 143-145 °C; IR (KBr) v/cm-1: 3389, 2947, 1713, 1537, 1468, 1356, 1281, 1189,
1110,	1033, 890, 774, 716; 1H NMR (300 MHz, CDCl3): 5H 0.99 (s, 18H, 2C(CH3)3), 1.29 (s, 18H, 2C(CH3)3), 2.57 (m, 4H, 2CH2), 3.35 (d, 4H, J = 12.9 Hz, ArCH2Ar),
3.86-3.90	(m, 4H, 2SCH2), 4.17 (m, 4H, 2OCH2), 4.24 (d, 4H, J = 13.3 Hz, ArCH2Ar), 6.86 (s, 4H, ArH), 7.07 (m, 4H, ArH), 7.60-7.64 (m, 4H, ArH), 7.68 (s, 2H, 2 x OH),
7.87-7.93	(m, 4H,ArH); 13C NMR (300 MHz, CDCl3): 5c 29.63, 29.65, 29.67, 29.69, 30.91, 30.95, 31.36, 31.39, 32.09, 32.85, 73.55, 124.41, 124.67, 125.63, 126.08, 131.29, 132.42, 133.52, 147.30, 149.16, 162.34, 165.77; DEPT 135o (125 MHz, CD2Cl2): 5 133.09, 132.45, 131.26, 126.14, 125.60,124.625, 124.52, 73.65, 32.03, 32.01, 31.34, 31.33, 30.94, 30.92, 29.68, 29.67, 29.64, 29.62; ESI-MS: m/z = 1176.49 [M+H]; Calcd: C, 66.53; H, 5.94; N, 7.51; S, 5.73%. Found: C, 66.35; H, 5.80; N, 7.37; S, 5.86%.
Synthesis of 5,11,17,23-Tetra-ieri-butyl-25,27-bis(5-(3-nitrophenyl)-1,3,4-oxadiazole-2-thiapropoxy)-26,28-dihydroxycalix[4]arene (6k):
White crystals; 0.134 g (45%), mp138-140 °C; IR (KBr) v/cm-1: 3332, 2945, 1723, 1537, 1470, 1354, 1289, 1196,
1111,	1028, 928, 718, 641, 581; 1H NMR (300 MHz, CDCl3): 5h 0.97 (s, 18H, 2C(CH3)3), 1.31 (s, 18H, 2C(CH3)3), 2.58 (m, 4H, 2CH2), 3.37 (d, 4H, J = 13.2 Hz, ArCH2A3 r3), 3.87 (m, 4H, 2SC2H2), 4.18 (m, 4H, 2OCH2), 4.25 (d, 4H, J = 12.9 Hz, ArCH2Ar), 6.86 (s, 4H, ArH), 7.08 (s, 4H, ArH), 7.55-7.59 (m, 4H, ArH), 7.67 (s, 2H, 2OH), 7.85-7.92 (m, 4H, ArH); 13C NMR (300 MHz, CDCl3): 5c 29.66, 30.13, 30.73, 31.18, 31.63, 32.21, 32.23, 33.97, 73.35, 118.32, 123.93, 124.71, 125.12, 125.52, 125.86, 126.13, 130.82, 133.69, 141.84, 147.32, 149.16, 162.32, 165.78; DEPT 135o (125 MHz, CD2Cl2): 5 133.69, 130.82, 126.13, 125.86, 125.52,125.13, 124.72, 123.93,118.35, 73.35, 33.98, 32.23, 32.21, 31.64, 31.18, 30.74, 30.12, 29.68; ESI-MS: m/z = 1174.5 [M-H]; Calcd: C, 66.53; H, 5.94; N, 7.51; S, 5.73%. Found: C, 66.28; H, 5.79; N, 7.29; S, 5.98%.
4. Conclusion
In summary, a series of new tetra-tert-butylca-lix[4]arene derivatives 4a-e and 6f-k were prepared by reaction of 1,2,4-triazole-5-thione 3a-e and 1,3,4-oxadia-zole-5-thione 5f-k moieties with calix[4]arene (2) in pre-
Ghezelbash and Dilmaghan: Synthesis of a Series of Novel ...
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Acta Chim. Slov. 2016, 63, 790-797	DOI: 10.17344/acsi.2016.2637
sence of sodium hydroxide at room temperature. The new calix[4]arene are reported in this article may have biological and pharmaceutical activities.
5. Acknowledgments
The authors are grateful to Urmia University for providing a fellowship for the present work and thanks are also given to Prof. Dr. Joachim Thiem from Hamburg University for the ESI-MS and DEPT measurements.
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Povzetek
Z reakcijo 1,2,4-triazol-5-tiona oz. 1,3,4-oksadiazol-5-tiona s 5,11,17,23-tetra-terc-butil-25,27-bis(3-bromopropoksi)-26,28-dihidroksikaliks[4]arenom (2) smo sintetizirali serijo tetra-ierc-butilkaliks[4]arenov derivatiziranih z 1,2,4-tria-zol-5-tionskimi oz. 1,3,4-oksadiazol-5-tionskimi fragmenti na spodnjem robu kaliksarena. Pripravljene spojine smo ka-rakterizirali z FT-IR, 1H NMR, 13C NMR spektroskopskimi podatki, elementno analizo in ESI-MS.
Ghezelbash and Dilmaghan: Synthesis of a Series of Novel ...