Synthesis and Studies of 1-[2-(Aryl Amino-2-Oxo Ethyl) Amino]-4-(N-Methyl Piperazino)-Benzene Derivatives

1-[2-(Aryl Amino-2-Oxo Ethyl) Amino]-4-(N-Methyl Piperazino)Benzene Derivatives were synthesized. The synthesized compounds were screened for their antibacterial activities against S.aures and E.coli by cup plat method. From screening result some compounds found highly active against both Gram-positive and Gram-negative bacteria while other compounds possess feeble to moderate activity.

Piperazine belongs to the family of medicines called anthelmintics.Anthelmintics are used in the treatment of worm infections.Piperazine derivatives have also been shown to possess diverse biological properties including antihistamine, anti katonic, anticonvulsant, anti HIV 1 and as potential cocaine-abuse therapeutic agent [2][3] .The two nitrogens of the piperazine molecules are present in rigid conformation structures, which probably favors their involvement to the dopamine receptors.
A large number of antibiotics contain amide linkage.Several derivatives of amides were prepared and found to possess antimicrobial activities.Literature survey revels that various drugs e.g.penicillin 4 (antibacterial), Pyrazinamide 5 (anti tubercular), Indinavir 6 , Ritonavir 7 etc.(protease inhibitors as anti AIDS) contains their particular activities due to the amide linkage present in their structures.Step-II Step-III

Aryl amine Chloro acetyl chloride N-Chloro acetyl aryl amines
Step-IV

Experimental
Step

-1 Preparation of N-[4-nitrophenyl]-N-methyl piperazine.
A mixture of N-methyl piperazine (0.01mole), 4-chloro nitro benzene (0.01mole) and anhydrous K 2 CO 3 in methanol was refluxed with stirring.After the completion of reaction the resultant mixture was cooled to room temperature.Then it was poured into ice-cold water with constant stirring.The solid separated was purified by recrystallisation.M.P. 220-222 o C.

Step-3 Preparation of N-Chloro acetyl aryl amines.
In benzene (30.ooml) chloro acetyl chloride (0.03M, 2.4ml.) was added and the mixture was stirred in water bath.The solution of aryl amines (0.02M) in benzene (30.0 ml) was added drop wise and refluxed for 2 hours.Then cooled the reaction mixture.The resulting white precipitates were filtered by recrystallisation from alcohol.Physical data of N-Chloro acetyl aryl amines are given in Table 1.

Step-4 Preparation of 1-[2-(Aryl amino-2-oxo ethyl) amino]-4-(N-methyl piperazino)-benzene.
A mixture of N-Chloro acetyl aryl amine (0.01M), N-[4-Amino phenyl-N-methyl piperazine (0.01M,1.91 gm.) and anhydrous K 2 C0 3 were refluxed in acetone.After the completion of reaction the resulting mixture was cooled to room temperature.Then it was poured in to ice cold water with constant stirring.The solid separated was purified by recrystallisation from ethanol.Physical and analytical data of title compound and its other substituted derivatives are given in Table-2

Results and Discussion
The entire synthesised compounds were screened for their antibacterial activities against S.aures and E.coli by cup plat method.Tetracycline and Chloramphenicol were used as standard drugs.The compounds were tested at the concentration of 40 µg/ml and DMF as a solvent.
From screening result it was observed that the compounds 2,4,6,7,10 found highly active against both Gram-positive and Gram-negative bacteria while other compounds possess feeble to moderate activity.Compounds 2,4,10 showed maximum zone of inhibition respectively (12,12,13) for E.coli while compounds 1,2 showed maximum zone of inhibition respectively (12,12) for S.aures as well as compound 6,8 showed maximum zone of inhibitions (11,11) for S.typhi respectively. Scheme

Table 1 .
. Physical and analytical data of n-chloroacetyl aryl amines

Table - 3
. Antibacterial activity of newly synthesized compounds Zone of inhibition in mm at 40 g/ml conc.