Microwave Assisted Synthesis and Antimicrobial Activities of Some 2-Amino-4-aryl-3-cyano-6-( 4 ’-hydroxy phenyl )-pyridines

4’-Hydroxy chalcones were treated with malononitrile in the presence of ammonium acetate under solventless microwave assisted condition to get 2-amino-4-aryl-3-cyano-6-(4’-hydroxy phenyl)-pyridines. The prepared compounds were screened for their antimicrobial activity; some of them have exhibited promising antimicrobial activity.


Introduction
The usage of microwave energy to accelerate the organic reactions is of increasing interest and offers several advantages over conventional heating techniques 1 .Synthesis under MWI can be achieved conveniently and rapidly under solventless conditions which holds a strategic position, as the solvents are often toxic, expensive, problematic to use and hazardous to environment.The reactions under microwave irradiation solventless condition are eco-friendly and are a part of green chemistry [2][3][4][5][6] .Literature survey reveals that phenyl substituted pyridines have been widely investigated due to their pharmaceutical usages.Among a wide variety of heterocycles that have been explored for developing pharmaceutically important molecules, cyanopyridines have played a crucial role in medicinal chemistry.Cyano pyridines were to possess a broad spectrum of biological activities such as antiviral 7 , CNS depressent 8 and bactericidal 9 etc. .
Literature survey reveals that among various chalcones, 4'-hydroxy chalcones have received little attention.Therefore, it was thought worthwhile to synthesize some new pyridine derivatives using this synthon, under non-conventional microwave assisted solventless condition.4'-Hydroxy chalcones (1a-g) were treated with malononitrile in presence of ammonium acetate to get 2-amino-4-aryl-3-cyano-6-(4'hydroxy phenyl)-pyridines (2a-g) (Scheme 1).The reaction was carried out under MWI solventless condition.For the sake of comparison same reaction was also carried out by conventional heating method under liquid phase in presence of ethanol as solvent.The products obtained by both MWI and conventional heating method were found to be identical.Under conventional heating the reaction time was 6-10 h with 70-72% yield, whereas under MWI conditions the reaction time was brought down up to 3-5 minutes with improved yield (85-88%), indicating the superiority of microwave assisted method over conventional heating.Furthermore the reaction under solventless condition is eco-friendly and thus avoiding solvent the whole process becomes economically viable.

Experimental
All the melting points reported are uncorrected and were taken in open capillaries.The IR spectra were recorded on Shimadzu IR spectrometer using KBr (υ cm -1 ).The PMR spectra were taken on Bruker DRx-600 spectrometer using TMS as internal standard and CDCl 3 as solvent; (chemical shifts in δ ppm); mass spectra (FAB) were recorded on Jeol Sx-600 mass spectrometer using m-nitro benzyl alcohol as matrix.The matrix peaks were observed at m/z 307, 289, 154, 137 and 136 respectively.All the transformations were carried out in domestic microwave oven Samsung 30 N. Chalcone (0.01 mole), malononitrile (0.01 mole) and ammonium acetate (0.08 mole) were mixed thoroughly to form an intimate mixture.It was subjected to microwave irradiation at 600 Watt power for 3-4 minutes with interruption after each 30 seconds.After completion of reaction is indicated by TLC, the reaction mixture was cooled to room temperature and poured into ice cold water.The separated solid was filtered off, dried and crystallized from alcohol as colourless crystals (Scheme 1).

Results and Discussion
New 2-amino-4-aryl-3-cyano-6-(4'-hydroxy phenyl)-pyridines were prepared by both MWI and conventional heating.The product obtained were characterized on the basis of their analytical and spectral data (Table 1 & 2) and the identity of compounds obtained was checked by m.m.p. and co.TLC.

Scheme 1 Table 1 .
Physical data of the synthesized compounds

Table 3 .
Biological screening results of compounds (2a-g), zone of inhibition in (mm)