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
Hindawi Publishing Corporation
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
Ali Darehkordi and Somayeh Ghazi
Department of Chemistry, Faculty of Science, Vali-e-Asr University of Rafsanjan, Rafsanjan 77176, Iran
Correspondence should be addressed to Ali Darehkordi;
Received 18 June 2012; Accepted 7 August 2012
Academic Editor: Sulekh Chandra
Copyright © 2013 A. Darehkordi and S. Ghazi. is 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.
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 4 with 1, 4ங -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.
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 [1–4]. It has also been reported in literature that
certain compounds bearing 1,3,4-oxadiazole/thiadiazole and
1,2,4-triazole nucleus possess signi�cant anti-in�ammatory
activity [5–7]. 4-iazolidinone derivatives are also known
to possess antibacterial [8–11], antifungal [12–14], antiviral [15–18], and antituberculosis [19–21] properties. 4iazolidinones have been reported as novel inhibitors of
the bacterial enzyme [22]. e 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. erefore, 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-in�ammatory, CNS stimulants,
sedatives, antianxiety, and antimicrobial agents [23, 24].
iosemicarbazone 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 1,2,4triazines were also found to possess signi�cant antifungal,
antibacterial, and insecticidal properties [25]. Five-member
rings are highly prevalent in the pharmacopoeia and more
generally in collections of bioactive compounds.
ere 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-in�ammatory,
2
Journal of Chemistry
O
O
Cl
Cl
Pyridine, R.T
O
H
N
H2 N
N
H
S
H
N
O
2
H
N
H2 N
Cl
Cl
NH2
S
S
Cl
NH2
H
N
O
NH2
N
H
S
H2 N
S
3
O
S
O
O
Cl
H
N
N H
NH2
Pyridine, R.T
1
N
H
O
O
O
S
H2 N
H
N
O
H N
N H
N
H
O
Cl
Pyridine, R.T
O
NH
HN
S
H2 N
4
S 1: Synthesis of carbonyl(phenyl) hydrazinecarbothioamide derivatives.
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. ese
derivatives can be used for synthesis of various dendrimers.
2. 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 NH2 , 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 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. 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 shis.
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�� -(benzene1,3,5-triyl)tris(4H-1,2,4-triazole-3-thiol) (4e), respectively.
ese compounds displayed IR, 1 H and 13 C-NMR spectra
(...truncated)
