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Journal of Chemistry
Volume 2013, Article ID 857956, 8 pages
http://dx.doi.org/10.1155/2013/857956
Research Article

Synthesis of a New Class of Tris- and Bis(1,3,4-thiadiazol-2-amine) Methyl and Ethyl Tris- and Bis-2-(2-(2-benzoyl hydrazinyl)-4-oxothiazolidine) Acetate Derivatives

Department of Chemistry, Faculty of Science, Vali-e-Asr University of Rafsanjan, Rafsanjan 77176, Iran

Received 18 June 2012; Accepted 7 August 2012

Academic Editor: Sulekh Chandra

Copyright © 2013 Ali Darehkordi and Somayeh Ghazi. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Hydrazine, carbothioamide derivatives 2, 3, and 4 were synthesized by the condensation of 1, 3, 5-tri carbonyl tri chloride, Terephthaloyl dichloride, and 1, 4-dicarbonyl chloride with thiosemicarbazide in presence of pyridine as a solvent. The reaction of compounds 2, 3, and 4 with DMAD or DEAD led to the formation of 4-oxothiozolidine derivatives (4b–c), (3a-c), and (2c-d). The treatment of compounds 2, 3, and 4 with 1, 4′-diboromoacetophenone resulted in the formation of thiazole derivatives (2g, 3f, 4f). The treatment of compounds 2, 3, and 4 with sulfuric led to the formation of 4H-1,2,4-triazole-3-thiol derivatives (2f, 3d, and 4d). The cyclization of compounds 2, 3, and 4 in the presence of 2N NaOH resulted in the formation of compounds 2e-4e containing two or three [1,2,4]triazole rings which are linked to the benzene ring. These compounds are important and useful monomer for synthesis of various dendrimers.

1. Introduction

Oxadiazole derivatives, an important group of heterocyclic compounds, have been the subject of extensive study in the recent years. Numerous reports have highlighted their chemistry and use [14]. It has also been reported in literature that certain compounds bearing 1,3,4-oxadiazole/thiadiazole and 1,2,4-triazole nucleus possess significant anti-inflammatory activity [57]. 4-Thiazolidinone derivatives are also known to possess antibacterial [811], antifungal [1214], antiviral [1518], and antituberculosis [1921] properties. 4-Thiazolidinones have been reported as novel inhibitors of the bacterial enzyme [22]. The incidence of tuberculosis is increasing worldwide, partly due to poverty and inequity and partly due to the HIV/AIDS pandemic, which greatly increase the risk of infectious proceeding to overt disease. During recent years, the microorganisms have developed increasing resistance against drugs. Therefore, there is a need to develop new, potent, fast-acting antimicrobial, antiviral and antimycobacterial drugs with low toxicity. Triazoles and in particular 1,2,4-triazole nucleus have been incorporated into a wide variety of therapeutically interesting drug candidates including anti-inflammatory, CNS stimulants, sedatives, antianxiety, and antimicrobial agents [23, 24]. Thiosemicarbazone and thiosemicarbazide derivatives are of considerable interest due to their antibacterial, antimalarial, antiviral, and antitumor activities. Heterocycles derived from thiosemicarbazide in the form of 1,2,4-triazoles and 1,2,4-triazines were also found to possess significant antifungal, antibacterial, and insecticidal properties [25]. Five-member rings are highly prevalent in the pharmacopoeia and more generally in collections of bioactive compounds.

There are a number of antimicrobial compounds containing a 1,2,4-triazole ring in their structures such as Fluconazole, Eperezolid, and Ravuconazole that are important antifungal drugs [26]. Heterocycles containing a 1,2,4-triazole or 1,3,4-thiadiazole moiety and the compounds consisting of 1,2,4-triazole and 1,3,4-thiadiazole condensed nucleus systems constitute a class of compounds possessing a wide spectrum of biological activities such as anti-inflammatory, antiviral and antimicrobial and antitumor properties [27, 28]. In view of these facts, the aim of this present study is to obtain tris- and bis[(1,3,4-thiadiazol-2-amine)], tris- and bis[2-(2-(2-benzoyl hydrazinyl) 4-oxothiazolidine)] derivatives incorporating also bis[(4-1, 2, 4-triazole-3-thiol)] structures (Schemes 2, 3, and 4) as antimicrobial agents. These derivatives can be used for synthesis of various dendrimers.

2. Results and Discussion

We started from carbonyl(phenyl) hydrazinecarbothioamide derivatives 2, 3, and 4. These compounds were obtained from reaction of 1,4-dicarbonyl chloride, Terephthaloyl dichloride, 1,3,5-tricarbonyl trichloride, and thiosemicarbazide in presence of pyridine (Scheme 1). The structures of compounds 2, 3, and 4 were deduced from their elemental analysis, their IR, 1H- and 13C-NMR spectra. In the 1H-NMR spectra of compounds 2, 3, and 4 the expected two peaks around 10 and 9 ppm corresponding to the two NH groups, two singles at 8 ppm corresponding to the NH2, and aromatic-H observed. Also their 13C-NMR showed signals of C=S, C=O, and aromatic carbons 182, 165, 133, 131 ppm, respectively.

857956.sch.001
Scheme 1: Synthesis of carbonyl(phenyl) hydrazinecarbothioamide derivatives.
857956.sch.002
Scheme 2: Synthesis of 2c–2g compounds from 1,4-dicarbonyl(phenyl)-bis(hydrazinecarbothioamide) 2.
857956.sch.003
Scheme 3: Synthesis of 3a–3f compounds from 1,3-dicarbonyl(phenyl)-bis(hydrazinecarbothioamide) 3.
857956.sch.004
Scheme 4: Synthesis of 4b–4f compounds from 1,3,5-tricarbonyl (phenyl) tris(hydrazine carbothioamide) 4.

In order to obtain oxothiazolidine derivatives a series of 4-oxothiazolidine-5-ylidene 4b-c, 3b-c, and 2c-d were synthesized (Schemes 24). Compounds 4b-c, 3b-c, and 2c-d were obtained by coupling dialkyl acetylenedicarboxylate with a series of hydrazinecarbothioamides in methanol as a solvent at ambient temperature. On the basis of well-established chemistry of electrophilic acetylenes, it is reasonable to assume that compounds 4b-c, 3b-c, and 2c-d result from the initial conjugate addition of the sulfur atom of 3 to the acetylenic ester and then the ester group of intermediate is attacked by the amino moiety to yield 4b-c, 3b-c, and 2c-d by elimination of ROH.

The H-NMR spectrum of 4c in DMSO showed five singlet for CH3, H–C=C, aromatic protons, N–H (hydrazone), and N–H(oxothiazolidine ring) at 3.79, 6.73, 8.61, 9.48, 11.52 ppm, respectively. The 13C-NMR spectrum of 4c showed eight signals in agreement with the proposed structure. Partial assignments of these resonances are given in the experimental section. The H- and C-NMR spectra 2c-d, 3a, 3b-c, and 4b are similar to those for 4c except for the ester moiety, which exhibit characteristic signals at appropriate chemical shifts.

The treatment of compound 4 with sulfuric acid and sodium hydroxide produced 5,5′,5′′-(benzene-1,3,5-triyl)tris(1,3,4-thiadiazol-2-amine) (4d) and 5,5′,5′′-(benzene-1,3,5-triyl)tris(4H-1,2,4-triazole-3-thiol) (4e), respectively. These compounds displayed IR, 1H and 13C-NMR spectra and elemental analyses consistent with the assigned structures. In the 1H-NMR spectrum of compound 4e, additional signal due to –SH group appeared at 13.89 ppm (controlled by changing D2O), while the 2 –NH– and –NH2 signals disappeared. Moreover, the IR spectrum of compound 4e displayed and –SH stretching band at 2714 cm−1. The hydrogen’s of the –NH2 group in compound 4d resonated at 7.60 ppm in the 1H-NMR spectrum. The –NH2 stretching band was observed at 3187 cm−1 in the IR spectrum. Synthesized compounds are useful and important derivatives for synthesis of different important dendrimers.

The synthesis of compounds 2 g, 3f, and 4f were carried out by the reaction of 2,4′-dibromoacetophenone with compounds 2, 3, and 4 in DMF as a solvent and ultrasound irradiation at ambient temperature. The 1H and 13C-NMR spectra of compounds 2g, 3f, and 4f displayed additional signals due to the aromatic ring derived from 2, 4′-dibromoacetophenone moiety at aromatic region, while the signal belonging to the –NH2 and –NH– groups of hydrazinecarbothioamide structure did not appear. In the 1H-NMR spectra of compounds 2g, 3f, and 4f two signals, each belonging to the two –NH– (O=C–NH–NH–) groups, observed between 11.03 and 11.15, 9.75 and 9.79 ppm, respectively. The signal belonging to thiazole ring protons (HC=C) and aromatic protons appeared between 7.30 and 7.34, 7.54, and 8.68 ppm, respectively, in the 1H-NMR spectrum of compounds 2g, 3f, and 4f. The 13C-NMR spectra of compounds 2g, 3f, and 4f showed signals in agreement with the proposed structures. Complete assignments of these resonances are given in the experimental section.

3. Experimental

3.1. Synthesis of 1,4-Dicarbonyl(phenyl)bis(hydrazinecarbothioamide) (2)

Terephthaloyl dichloride (20 mmol) in pyridine (5 mL) was stirred at room temperature for 10 min. Then a mixture of thiosemicarbazide (40 mmol) in pyridine (5 mL) was added drop wise to these and then stirred at ambient temperature for 24 hours. The pyridine was removed under reduced pressure. To the residue, was added water, and the precipitate was filtered, washed with water and recrystallized from DMF to afford the desired product (2).

According to the procedure, compound 2 was obtained as white powder. Yield: 92%. Mp: 234–236°C. 1H-NMR (DMSO-d6, 500 MHz): δ (ppm) = 7.95 (d, J = 8.3, 2H, Ar–H), 7.95 (d, J = 8.3, 2H, Ar–H), 8.62 (s, 2H. NH2), 9.48 (s, 1H, NH), 10.54 (s, 1H, NH).13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 131.27, 133.78 (4C, Arom), 165.73, 182.45 (2C, C=O, C=S). Anal. Calcd. for C10H12N6O2S2 C, 38.45; H, 3.87; N, 26.90. Found: C, 38.12; H 3.90; N, 27.08%.

3.2. General Procedure for the Preparation of 1,4-Benzoyl-bisalkyl 2-(2-hydrazono)-4-oxothiazolidine-5-ylidene)acetate (2c-d)

A mixture of 1,4-benzoyl-bis-hydrazinecarbothioamide (1 mmol) and methanol (8 mL) was stirred at ambient temperature for 15 min. Then a solution of DMAD or DEAD (2 mmol) and methanol (2 mL) was added drop wise to it. The reaction mixture was stirred at ambient temperature for 20 hr. The produced solid was filtered off and recrystallized by DMF to give the desired compounds (2c-d).

3.3.  1,4-Dicarbonyl(phenyl)bis(methyl-2-((Z)-2-hydrazono-4-oxothiazolidine-5-ylidene) acetate) (2d)

Yellow powder. Yield: %89, m.p 270–273°C. 1H-NMR (DMSO-d6, 500 MHz): δ (ppm) = 3.78 (s, 6H, 2-OCH3), 6.88 (s, 2H, H–C=C), 8.46 (d, J = 8.1, 4H, Ar–H), 10.37 (s, 1H, NH), 11.63 (s, 1H, NH). 13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 52.06, (2C, –OCH3), 128.61, 132.02, 137.01, 139.58 (10C, 6Arom, 4CH=C), 146.90, 164.13, 174.08. Anal. Calcd. for C20H16N6O8S2: C, 45.11; H, 3.03; N, 15.78. Found: C, 45.37; H, 3.12; N, 15.94%.

3.4.  1,4-Dicarbonyl(phenyl)bis(ethyl-2-((Z)-2-hydrazono-4-oxothiazolidine-5 ylidene) acetate) (2c)

Yellow powder. Yield: %88, m.p 265°C. 1H-NMR (DMSO-d6, 500 MHz): δ (ppm) = 1.24 (t, J = 7.1, 6H, –CH3), 4.24 (q, J = 7.1, 4H, –CH2–), 6.69 (s, 2H, H–C=C), 7.97 (d, J = 8.13, 4H, Ar–H), 10.50 (s, 1H, NH), 11.34 (s, 1H, NH).13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 14.24 (2C, 2-CH3), 62.04 (2C, 2CH2), 128.80, 132.49, 137.66, 139.72, (8C, 6Arom, C=C), 146.97, 164.56, 166.30, 174.08 (8C, 6C=O, 2C=N). Anal. Calcd. For C22H20N6O8S2: C, 47.14; H, 3.60; N, 14.99. Found: C, 47.63; H, 3.52; N, 15.06%.

3.5. Synthesis of N′1,N′4,-Bis(5-(4-boromophenyl) Thiazole-2(3H)-ylidene) Isophthaloyl Hydrazide (2 g)

A mixture of 1, 4-benzoyl-bis-hydrazinecarbothioamide (0.5 mmol) and DMF (3 mL) was prepared under ultrasonic for 15 min until fluoresced. Then a solution of 1,4′- diboromoacetophenone (1 mmol) and DMF (2 mL) drop wise was added to it. After 100 min the reaction completed (reaction accession controlled by TLC chromatography). Finally put the vessel in refrigerator for 1 hour. The precipitate was filtered and recrystallized from ethyl acetate, to give the desired compounds (2 g).

Brown powder. Yield: %96, m.p 290°C.1H-NMR (DMSO-d6, 500 MHz): δ (ppm): 7.34 (s, 2H, H-thiazol ring), 7.57 (d, J = 8.4, 4H, Ar–H), 7.78 (d, J = 8.4, 4H, Ar–H), 8.04 (m, 4H, Ar–H), 9.75 (s,2H, NH), 11.03 (s, 2H, NH). 13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 104.48 (2C, C= thiazol rings), 120.48, 127.70, 131.46, 133.78, 135.37, 137.12 (18C, arom, C=C), 149.41, 165.76, 172.34 (6C, 2 =CH, 2C=N, 2C=O). Anal. Calcd. For C26H18Br2N6O2S2: C, 46.58; H, 2.71; N, 12.54. Found: C, 46.78; H, 2.76; N, 12.15%.

3.6. Synthesis of 5,5′-(1,4-Phenylene) Bis(4-1,2,4-triazole-3-thiol) (2f)

A mixture of 1, 4-benzoyl-bis- hydrazine carbothioamide (1 mmol) and methanol (8 mL) was stirred at ambient temperature for 15 min. Then a solution of 15% sodium hydroxide (5 mL) was added and refluxed for 1 h. After the reaction completed the mixture was cooled to the room temperature and then acidified to pH 7 with acetic acid (1 N). The precipitate was filtered, washed with water, and recrystallized from DMF, to afford the desired compound (2f).

White powder. Yield: 95%. m.p = 320°C. 1H-NMR (DMSO-d6, 500 MHz): δ (ppm) = 8.01 (d, J = 8.3, 4H, Arom), 13.74 (s, 2H, NH), 13.89 (s, 2H, SH). 13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 128.23 (4C, Arom), 133.16 (2C, Arom), 160.43, 167.31 (4C, triazol ring). Anal. Calcd. For C10H8N6S2 C, 43.46; H, 2.92; N, 30.41. Found: C, 43.06; H, 2.80; N, 30.7%.

3.7. Synthesis of 5,5′-(1,4-Phenylene) Dithiophen-2-amine (2e)

1,4-Benzoyl-bis-hydrazinecarbothioamide (1 mmol) in 10 mL concentrated sulfuric acid (was cooled to the 0°C temperatures) was stirred for 15 min, and then left for another 10 min at room temperature. The resulting solution was poured slowly into ice-cold water, made alkaline to pH 8 with aqueous ammonia and the precipitated product was filtered, washed with water, and recrystallized from DMF.

White powder m.p = 290°C. Yield: 87%. 1H-NMR (DMSO-d6, 500 MHz): δ (ppm) = 7.08 (s, 4H, NH2)′ 7.82 (d, J = 8.2, 4H, Arom-H). 13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 129.45 (4C, Arom), 135.07 (2C, Arom), 163.34, 175.23 (4C, thiazol ring). Anal. Calcd. For C10H8N6S2 C, 43.46; H, 2.92; N, 30.41. Found: C, 43.01; H, 2.76; N, 30.58%.

3.8.  1,3-Dicarbonyl(phenyl)-Bis(hydrazinecarbothioamide) (3)

White powder. Yield: %89, m.p 119-120°C. 1H-NMR (DMSO-d6, 500 MHz): δ (ppm) = 8.72 (s, 4H, NH2), 7.69 (m, 1H, Ar–H), 8.12 (d, J = 8.0, 2H, Ar–H), 8.48 (s, 1H, Ar–H), 9.53 (s, 2H, NH), 10.58 (s, 2H, NH). 13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 129.56, 131.00, 132.4, 134.07 (6C, Arom), 165.23, 183.11 (2C, C=O, C=S). Anal. Calcd. For C10H12N6O2S2: C, 38.45; H, 3.87; N, 26.90. Found: C, 38.21; H, 3.67; N, 27.17%.

3.9. Ethyl 2-(2-(2-(3-(2-carbamothioylhydrazinecarbonyl)benzoyl)hydrazono)-4-oxothiazolidine-5-ylidene)acetate (3a)

Yellow powder. Yield: %69, m.p 280°C. 1H-NMR (DMSO-d6, 500 MHz): δ (ppm) = 1.25 (t, J = 7.1, 3H, CH3), 6.69 (s, 1H, H–C=C), 7.90 (m, 1H, Ar–H), 7.97 (s, 1H, Ar–H), 8.01 (d, J = 8.23, 2H, Ar–H), 8.04 (s, 2H, NH2), 9.37 (s1H, NH), 9.51 (s1H, NH), 11.28 (s, 1H, NH).13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 14.86 (1C, -CH3), 62.38 (C, CH2), 124.78, 131.09, 131.63, 132.41, 133.89, 134.57, 136.14(8C, Arom, C=C), 147.19, 164.80, 164.96, 166.15, 175.16, 182.91 (6C,C=N, C=O, C=S). Anal. Calcd. For C16H16N6O5S2: C, 44.03; H, 3.69; N, 19.25. Found: C, 43.71; H, 3.96; N, 19.65%.

3.10.  1,3-Dicarbonyl(phenyl)bis(methyl-2-((Z)-2-hydrazono-4-oxothiazolidine-5-ylidene) acetate (3b)

Yellow powder. Yield: %92, m.p 223–226°C. 1H-NMR (DMSO-d6, 500 MHz): δ (ppm) = 3.80 (s, 6H, 2-OCH3), 6.72 (s, 2H, H–C=C), 7.69 (m, 1H, Ar–H), 8.10 (d, 2H, J = 7.8, 2H, Ar–H), 8.39 (s, 1H, Ar–H), 10.90 (s, 2H, NH), 11.41 (s, 2H, NH). 13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 52.12, (2C, –OCH3), 129.43, 132.27, 135.12, 140.04 (8C, Arom, CH=C), 147.02, 164.50, 166.58, 174.83 (8C, C=N, C=O).). Anal. Calcd. For C20H16N6O8S2: C, 45.11; H, 3.03; N, 15.78. Found: C, 45.66; H, 3.19; N, 15.42%.

3.11. N′1,N′4-Bis(5-(4-bromophenyl)thiazol-2-yl)isophthalohydrazide (3f)

Yield: %96, m.p 290. 1H-NMR (DMSO-d6, 500 MHz): δ (ppm):7.32 (s, 2H, thiazol rings), 7.59 (d, J = 8.4 Hz, 4H, Ar–H), 7.80 (d, J = 8.4, 4H, Ar–H), 7.87 (m, 1H, Ar–H), 8.14 (m, 2H, Ar–H), 8.30 (s, 1H, Ar–H). 13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 105.03 (2C, C= thiazol rings), 120.35, 130.36, 131.78, 133.46, 133.65, 135.42, 134.60, 137.52 (18C, arom, C=C), 149.48, 165.80, 173.08 (6C, 2 =CH, 2C=N, 2C=O). Anal. Calcd. For C26H18Br2N6O2S2: C, 46.58; H, 2.71; N, 12.54. Found: C, 46.27; H, 2.9; N, 15.42%.

3.12.  5,5′-(1,3-Phenylene)bis(4H-1,2,4-triazole-3-thiol) (3d)

White powder m.p = 315°C. Yield: 62%. 1H-NMR (DMSO-d6, 400 MHz): δ (ppm) = 7.56 (d, 2H J = 6.4, Arom-H), 7.94 (m, 1H,Arom-H), 8.46 (s, 1H, Arom-H), 13,47(s, 2H, SH). 13C-NMR (DMSO-d6, 100 MHz): δ (ppm) = 124.32, 132.18, 128.52, 130.64 (6C, Arom), 158.55, 160.13 (4C, 4C=N). Anal. Calcd. For C10H8N6O3S3: C, 43.46; H, 2.92; N, 30.41. Found: C, 43.17; H, 3.06; N, 30.82%.

3.13. Synthesis of 1,3,5-Tricarbonyl(phenyl) tris(hydrazinecarbothioamide) (4)

A mixture of 1,3,5-tri carbonyl trichloride (20 mmol) in pyridine (5 mL) was stirred at room temperature for 10 min. Then a mixture of thiosemicarbazide (60 mmol) in pyridine (10 mL) was added drop wise to it, and then stirred for 24 hours. The pyridine was removed under reduced pressure. To the residue, was added water and the precipitate was filtered, washed with water, and recrystallized from DMF to afford the desired product (4).

Cream powder. Yield: %90. m.p 168–170. 1H-NMR (DMSO-d6, 500 MHz): δ (ppm) = 8.63 (s, 6H, NH2), 8.79 (s, 3H, Ar–H), 9.48 (s, 3H, NH), 10.48 (s, 3H, NH),13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 131.21, 133.73 (6C, Arom), 165.79, 182.87 (6C, 3C=O, 3C=S). Anal. Calcd. For C12H15N9O3S3: C, 33.56; H, 3.52; N, 29.35. Found: C,33.07; H, 3.65; N, 29.77%.

3.14. General Procedure for the Synthesis of 1,3,5-Benzoyl-tris-alkyl 2-(hydrazono)-4-oxothiazolidine-5-ylidene) Acetate (4c, 4d)

A mixture of 1,3,5-benzoyl trishydrazine carbothioamide (0.5 mmol) and methanol (8 mL) was stirred at room temperature for 15 min. Then a solution of DMAD or DEAD (1.5 mmol) and methanol (2 mL) was added drop wise to it. The reaction mixture was then stirred at ambient temperature for 22 hr. The separated solid was filtered off and recrystallized by DMF to give the desired compounds.

3.15.  1,3,5-Benzoyl-tris-ethyl 2-(2-Hydrazono)-4-oxothiazolidine-5-ylidene)acetate (4d)

Yellow powder. Yield: %72, m.p 245°C (decom.). 1H-NMR (DMSO-d6, 500 MHz): δ (ppm) = 3.79 (s, 9H, –OCH3), 6.73 (s, 3H, H–C=C), 8.61 (s, 3H, Ar–H), 9.48 (s, 3H, NH), 11.52 (s, 3H, NH).13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 52.43 (3C, –OCH3), 129.61, 132.61,134.57, 139.66 (8C, Arom, CH=C), 147.15 (3C, C=N thiazole), 164.07. 166.62, 175.23 (9C, C=O). Anal. Calcd. For: C30H27N9O12S3 C, 44.94; H, 3.39; N, 15.72. Found: C,45.07; H, 3.75; N, 16.11%.

3.16.  1,3,5-Tricarbonyl(phenyl)tris(methyl-2-((E)-2-hydrazono-4-oxothiazolidine-5-ylidene)acetate) (4c)

Yellow powder. Yield: %72, m.p 245°C (decom). 1H-NMR (DMSO-d6, 500 MHz): δ (ppm) = 3.79 (s, 9H, –OCH3), 6.73 (s, 3H, H–C=C), 8.61 (s, 3H, Ar–H), 9.48 (s, 3H, NH), 11.52 (s, 3H, NH).13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 52.43 (3C, –OCH3), 129.61, 132.61,134.57, 139.66 (8C, Arom, CH=C), 147.15 (3C, C=N thiazole), 164.07. 166.62, 175.23 (9C, C=O). Anal. Calcd. For C27H19N9O12S3: C, 42.69; H, 2.79; N, 16.59. Found: C, 43.01; H, 3.11; N, 16.35%.

3.17. Synthesis of 5,5′,5′′-(Benzene-1,3,5-tril) Tris(1,3,4-thiadiazole-2-amine) (4e)

A mixture of 1,3,5-benzoyl-tris-hydrazinecarbothioamide (0.5 mmol) and methanol (8 mL) was stirred at room temperature for 15 min. Then a solution of 15% sodium hydroxide (5 mL) was added and refluxed for 1 h. The reaction mixture was cooled and then acidified to pH 7 with acetic acid (1 N).The precipitate was filtered, washed with water, and recrystallized from DMF, to give the desired compound (4e).

White powder. Yield: %61, m.p 310°C (decom). 1H-NMR (DMSO-d6, 500 MHz): δ (ppm) = 7.60 (s, 6H, NH2), 8.06 (s, 3H, Ar–H). 13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 124.82, 133.44 (6C, Arom), 155.66, 170.06 (6C, 6C=N). Anal. Calcd. For C12H9N9S3: C, 38.39; H, 2.42; N, 33.58. Found: C, 38.14; H, 2.32; N, 33.67%.

3.18. Synthesis of 5,5′,5′′-(Benzene-1,3,5-tril) Tris (4-1,2,4-thriazole-3-thiol) (4d)

A mixture of 1, 3, 5-benzoyl-tris-hydrazine carbothioamide (1 mmol) and concentrated sulfuric acid (10 mL) in ice-cold water was stirred for 15 min, and then was refluxed for 2 hours. The resulting solution was poured slowly into ice-cold water, made alkaline to pH 8 with aqueous ammonia and the precipitated product was filtered, washed with water, and recrystallized from DMF.

Brown powder. Yield: %58, m.p 320°C. 1H-NMR (DMSO-d6, 500 MHz): δ (ppm) = 8.37 (3H, Ar–H), 13.05 (s, 3H, SH). 13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 124.87, 133.70 (6C, Arom), 158.96, 160.32 (6C, 6C=N). Anal. Calcd. For C12H9N9S3: C, 38.39; H, 2.42; N, 33.58. Found: C, 38.18; H, 2.33; N, 33.77%.

3.19. Synthesis of N′1,N′3,N′5-Tris(4-boromophenyl)thiazole-2(3H)-ylidene)benzene-1,3,5-thricarbonyl Hydrazide (4f)

A mixture of 1, 3, 5-tricarbonyl (phenyl)tris(hydrazine carbothioamide) (0.5 mmol) and DMF (3 mL) was prepared under ultrasonic for 15 min until fluoresced. Then a solution of 1,4′-diboromoacetophenone (1.5 mmol) and DMF (2 mL) was added to it drop wise. After 100 min the reaction completed (reaction accession controlled by TLC chromatography). Finally put the vessel in refrigerator for 1 hour. The precipitate was filtered and recrystallized from ethyl acetate, to give the desired compound (4f).

Brown powder. Yield: %86, m.p 330°C. 1H-NMR (DMSO-d6, 500 MHz): δ (ppm) = 7.30 (s, 3H, thiazol rings), 7.64 (d, J = 8.3 Hz, 6H, Ar–H), 7.83 (d, J = 8.3 Hz, 6H, Ar–H), 8.68 (s, 3H, Ar–H), 9.79 (s, 3H, NH), 11.15 (s, 3H, NH).13C-NMR (DMSO-d6, 125.77 MHz): δ (ppm) = 106.22 (3C, C= thiazol rings), 121.02, 132.83, 133.44, 134.21,136.98, 139.03 (24C, arom), 150.74, 166.59, 174.39 (12C, CH= thiazol rings, C=N, C=O). Anal. Calcd. For C36H24Br3N9O3S3: C, 44.74; H, 2.50; N, 13.04. Found: C, 45.07; H, 2.64; N, 12.79%.

Acknowledgment

The authors gratefully acknowledge the financial support for this paper, of Vali-e-Asr University of Rafsanjan, Faculty Research Grant.

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