Microwave-Assisted Synthesis
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1,2,4-Triazole and its derivatives are found to be associated with various biological
activities4. For example, fluconazole is used as an antimicrobial drug, while vorozole,
letrozole and anastrozole are nonsteroidal used for treatment of cancer and loreclezole is
used as an anticonvulsant5. Also 4-amino-1,2,4-triazoles are potentially good corrosion
inhibitors6. These compounds can be prepared by the nucleophilic attack of hydrazine
derivatives on nitriles7,8. Additionally, diazonium salts of heterocycles coupled with
2,4-pentanedione have been used as precursor in the synthesis of antimicrobial triazines9.
Rosenberg’s discovery10 of the important Pt-containing antitumor drug ciplatin led to the
search for other metal ions that could complex with biomolecules and exhibit carcinostatic
properties. Since the chemical nuclease activity of transition metal complexes was discovered
in the 1980s11 studying the interaction model and the mechanism of transition metal complexes
with DNA and exploring the application of metal complexes in antineoplastic medication,
molecular biology and bioengineering have become hotspots in recent years.
Based on the above literature precedents and importance of ligand-metal system, we
chose to synthesize 3,5-disubstituted-4-amino-1,2,4-triazole by conventional means as well
as Microwave irradiation method, followed by diazotization and coupled with 2,4-pentanedione.
The ligand was further complexed with Ni(II), Cu(II) and Ru(III) chlorides and screened
against cancerous cell lines.
Experimental
Melting points are uncorrected. IR spectra were recorded on Thermo Nicolet FT IR
spectrophotometer at Andhra University, 1H NMR spectra were taken on Perkin Elmer R-32,
90 MHz in DMSO-d6 using TMS as internal reference at IICT, Hyderabad and ESR spectra
were taken on Varian E 112 at room temperature and as well as liquid nitrogen temperature
using DPPH as standard at IIT Chennai. Benzyl cyanide, hydrazine hydrate, ethylene glycol
and 2,4-pentanedione were purchased from Across. All the solvents were of analytical grade
and were distilled before use. Microwave irradiation was carried out using a domestic
microwave oven. All the complexes were analyzed for the metal content by standard
procedure. Elemental analyses were carried out at Micro Analytical Center at Andhra
University. The HPLC was recorded using Shimadzu LC 6A with Shimpack silica gel
column. Anticancer screening was done at department of Biotechnology, Mother Teresa
Women’s University, Kodaikanal, on Jurkat, Raji & PBMC cell lines.
Synthesis of 3,5-dibenzyl-4-amino-1,2,4-triazole(2)
In conventional method of synthesis a mixture of benzyl cyanide (2 mmol), hydrazine
hydrate (1 mmol) and ethylene glycol (5 mL) were heated under reflux for 10 h. After
cooling 5 mL of HCl was added and again refluxed for 4 h, 3,5-dibenzyl-4-amino-1,2,4-
triazole(2) was isolated and characterized.
Two different MW reaction routes were adopted to synthesize 3,5-dibenzyl-4-amino-
1,2,4-triazole. In first method12 benzyl cyanide (2 mmol) and hydrazine hydrate (1 mmol)
were irradiated under microwave irradiation in presence of ethylene glycol (5 mL) for 9 min
at 300 W.The product was worked up and dark pink colored dihydro-1,2,4,5-tetrazine (1),
(Scheme 1) formed, which rearranges on treatment under acidic conditions into the 3,5-
dibenzyl 4-amino-1,2,4-triazole (2). In the second method13 benzyl cyanide (2 mmol),
hydrazine hydrate (1 mmol), hydrazine dihydro chloride (0.5 mmol) and ethylene glycol
(5 mL) were mixed together and irradiated under microwave condition for 8 min at 250W.
The addition of ethylene glycol led to form homogeneous solution and resulted the
formation of (2) (Scheme 2) via intermediate (1)
Jha, Anjali
