Synthesis and Antimicrobial Activities of Some New Thieno and Furopyrimidine Derivatives

Fused pyrimidines, 8,9-dimethyl[1,2,4]triazolo[4,3-c]thieno[3,2-e]pyrimidine 5, 3,8,9trimethyl[1,2,4]triazolo[4,3-c]thieno[3,2-e]pyrimidine 6, 4-benzylidinehydrazono-5,6 dimethylthieno[2,3-d]pyrimidine 7, 4-[4-hydroxybenzylidine]hydrazono-5,6-dimethylthieno[2,3-d]pyrimidine 8, 4-[4-tolylidin]hydrazono-5,6-dimethylthieno[2,3-d]pyrimidine 9, 4-[4-nitrobenzylidine]hydrazono-5-ethyl-6-methylthieno[2,3-d]pyrimidine 10 and 4-[4chlorobenzylidine]hydrazono-5-ethyl-6-methylthieno[2,3-d]pyrimidine 11 are prepared in good yield by an initial treatment of 2-amino-4,5-dimethylthiophene-3-carbonitrile 1 with formic acid, affording 5,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one 2, which is chlorinated with thionyl chloride and then hydrazinated with hydrazine hydrate. Finally hydrazino compound 4 is reacted with formic acid, acetic anhydrate, benzaldehyde, phydroxybenzaldehyde, p-toluayldehyde, p-nitrobenzaldehyde and p-chlorobenzaldehyde to give thienotriazolopyrimidines 5-6 and thienopyrimidines 7-11 respectively. All the compounds have been screened for their antimicrobial activity.


Physical measurements
Melting points were recorded with Electrothermal melting point apparatus and are uncorrected.Evaporation of solvents were performed under reduced pressure on a Buchi rotary evaporator.Thin layer chromatography was performed on Kieselgel GF 254 and visualization was accomplished by Iodine Flask or UV Lamp.Column chromatography was carried out with silica gel G 60 (100-200 mesh). 1 H-NMR (400 MHz) and 13 C-NMR (400 MHz) spectra were recorded for solutions in deuterio chloroform CDCl 3 , deuterio methanol CD 3 OD and deuterio dimethylsulphoxide (DMSO-d 6 ) (CD 3 ) 2 SO as solvent.

Synthesis of 3,8,9-trimethyl
An equimolar amount of hydrazino compound 4 (0.89g, 5 mmol) and acetic anhydrate (5 mmol) in methanol (20 ml) was refluxed at 65°C for about 2 hours with continuous stirring.The reaction mixture was then concentrated and left to cool overnight to room temperature for complete precipitation.The separated solid was then filtered off, dried and recrystallized from methanol to give compound 6 (0.71g, 65.4%) as brown crystals, m.p.

Antimicrobial activity
The inhibition zone of the micro-organisms due to the treatment of different synthesized compounds are mentioned in Tables 1 to 3. It was found that the inhibition zone of the compounds 5, 6 and 10 were more effective than that of other chemicals for all bacterial strain.They exhibited stronger activity than ampicillin also towards Bacillus Subtilis and Shigella dysenteriae.Other compounds were either inactive or moderately to fairly active against the tested bacterial strain.
As far as antifungal activity is concerned, all compounds showed good to excellent activity against all the fungi.Especially, it could be stressed that the test chamicals 5 and 6 exhibited even stronger activity than nystatin against Macrophomina phaseolina and Alternaria alternata.From the observation of inhibitions of the tested compounds, it was ascertained that, generally triazolothienopyrimidine derivatives 5-6 exhibited higher activities against human pathogenic bacteria and phytopathogenic fungi.

Conclusion
In this work, we have demonstrated that cyclisation with pyrimidine ring from oaminonitirile afforded thienopyrimidines and furopyrimidines with promising antibacterial and antifungal activity.The activity data obtained during the study will be certainly useful to go for further research for drug designing and synthesizing new fused pyrimidines.
Scheme I

Table 1 .
Antibacterial screenings (gram positive) of the test compounds.

Table 2 .
Antibacterial screenings (gram negative) of the test compounds.