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

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. e 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). e treatment of compounds 2, 3, and 4with 1, 4 -diboromoacetophenone resulted in the formation of thiazole derivatives (2g, 3f, 4f). e 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). e 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. ese compounds are important and useful monomer for synthesis of various dendrimers.


Results and Discussion
We started from carbonyl(phenyl) hydrazinecarbothioamide derivatives 2, 3, and 4. ese 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).e structures of compounds 2, 3, and 4 were deduced from their elemental analysis, their IR, 1 H-and 13 C-NMR spectra.In the 1 H-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 NH 2 , and aromatic-H observed.Also their 13 C-NMR showed signals of C=S, C=O, and aromatic carbons 182, 165, 133, 131 ppm, respectively.In order to obtain oxothiazolidine derivatives a series of 4-oxothiazolidine-5-ylidene 4b-c, 3b-c, and 2c-d were synthesized (Schemes 2-4).Compounds 4b-c, 3b-c, and 2cd were obtained by coupling dialkyl acetylenedicarboxylate with a series of hydrazinecarbothioamides in methanol as a solvent at ambient temperature.On the basis of wellestablished 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.e H-NMR spectrum of 4c in �MSO showed �ve singlet for CH 3 , 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.e 13 C-NMR spectrum of 4c showed eight signals in agreement with the proposed structure.Partial assignments of these resonances are given in the experimental section.e 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 shis.
e 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.ese compounds displayed IR, 1 H and 13 C-NMR spectra and elemental analyses consistent with the assigned structures.In the 1 H-NMR spectrum of compound 4e, additional signal due to -SH group appeared at 13.89 ppm (controlled by changing D 2 O), while the 2 -NH-and -NH 2 signals disappeared.Moreover, the IR spectrum of compound 4e displayed and -SH stretching band at 2714 cm −1 .e hydrogen's of the -NH 2 group in compound 4d resonated at 7.60 ppm in the 1 H-NMR spectrum.e -NH 2 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.e 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.e 1 H and 13 C-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 -NH 2 and -NH-groups of hydrazinecarbothioamide structure did not appear.In the 1 H-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.e 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 1 H-NMR spectrum of compounds 2g, 3f, and 4f.e 13 C-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.

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.en 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.e pyridine was removed under reduced pressure.To the residue, was added water, and the precipitate was �ltered, washed with water and recrystallized from DMF to afford the desired product (2).

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.en a mixture of thiosemicarbazide (60 mmol) in pyridine (10 mL) was added drop wise to it, and then stirred for 24 hours.e pyridine was removed under reduced pressure.To the residue, was added water and the precipitate was �ltered, washed with water, and recrystallized from DMF to afford the desired product (4).
Cream powder.Yield: %90.m.p 168-170.(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.en a solution of DMAD or DEAD (1.5 mmol) and methanol (2 mL) was added drop wise to it.e reaction mixture was then stirred at ambient temperature for 22 hr.e separated solid was �ltered off and recrystallized by DMF to give the desired compounds.A mixture of 1, 3, 5-benzoyl-trishydrazine carbothioamide (1 mmol) and concentrated sulfuric acid (10 mL) in ice-cold water was stirred for 15 min, and then was re�uxed for 2 hours.e resulting solution was poured slowly into ice-cold water, made alkaline to pH 8 with a�ueous ammonia and the precipitated product was �ltered, washed with water, and recrystallized from DMF.