Synthesis and antimicrobal activities of some novel triazolo[1,5-a]pyrimidine derivatives

A convenient synthesis of substituted 1,2,4-triazolo[1,5-a]pyrimidine was carried out by the reaction of various ketene dithioacetals with 5-amino 1,2,4-triazole in methanol in presence of sodium methoxide. The newly synthesized compound were characterized by 1H NMR, 13 C NMR, IR, MS, elemental analysis and screened for their antimicrobial activity against various strains of bacteria and fungi.


EXPERIMENTAL
Thin-layer chromatography was accomplished on 0.2 mm precoated plates of silica gel G60 F254 (Merck). Visualization was made with UV light (254 and 365 nm) or with an iodine vapor. IR spectra were recorded on a FTIR-8400 spectrophotometer using DRS prob. 1 H (400 MHz), 13 C (100 MHz) NMR spectra were recorded on a Bruker AVANCE II spectrometer in CDCl 3 and DMSO. Chemical shifts are expressed in δ ppm downfield from TMS as an internal standard. Mass spectra were determined using direct inlet probe on a GCMS-QP 2010 mass spectrometer (Shimadzu). Solvents were evaporated with a BUCHI rotary evaporator. Melting points were measured in open capillaries and are uncorrected.

General synthesis of 4-methyl-3-oxo-N-arylpentanamide (Int 1a-t);
A mixture of aromatic amine (10 mmol), methyl 4-methyl-3-oxopentanoate (10 mmol) and catalytic amount of sodium or potassium hydroxide lie (10 %) in toluene (50 ml) was refluxed at 110 °C for 12-15 h. The reaction was monitored by TLC. After completion of reaction, the solvent was removed under reduce pressure and washed with water to afford pure product.

General synthesis of ketene dithioacetals (Int 2a-t);
To a well stirred suspension of 4methyl-3-oxo-N-arylpentanamide (10 mmol) and potassium carbonate (20 mmol) in DMF (20 mL) at 0-5 °C was added CS 2 (10 mmol) over a period of 30 min. After completion of the addition, the reaction mixture was stirred at 0-5 °C for 1 h. Appearance of reddish solid in the reaction medium indicated the formation of dipotassium salt. To this reaction, a solution of methyl iodide (20 mmol) was added drop wise within 15 min at 0-5 °C. The mixture was allowed to warm at room temperature and stirred for 15 h, and then poured onto crushed ice under stirring. The separated solid was washed with water and collected by filtration.

General synthesis of triazolopyrimidine (3a-t);
To a solution of sodium methoxide in methanol (10 mL) ketene dithioacetal (5 mmol) and 5-amino-1,2,4-triazole were added at 0-5 °C. The reaction mixture then refluxed for 2-4 hours. The reaction was monitored by TLC. After the completion of reaction mixture was poured into cold water and the separated solid was dried and purified by column chromatography using ethylacetate and hexane.

RESULT AND DISCUSSION
Various methodologies have been described for the synthesis of 1,2,4-triazolo[1,5a]pyrimidines. During the course of our ongoing interest on synthesis of various heterocyclic compounds using α-oxo ketene dithioacetals, we observed that α-oxo ketene dithioacetals are versatile intermediate for the synthesis of triazolopyrimidines.

CONCLUSION
In summary, we have described the synthesis of substituted triazolopyrimidine derivatives in moderate yield. The reaction of various α-oxo ketene dithioacetals with 5amino-1,2,4-triazole was afforded the triazolopyrimidine derivatives in moderate to good yield in the presence of base. Sodium methoxide was found as an efficient base. All the synthesized compounds were evaluated for their antimicrobial activity. The investigation of antimicrobial and antifungal screening data revealed that all the tested compounds showed moderate to significant activity.