The aim of the present work is the synthesis of new derivatives of N-substituted diphenyl amine.The Scheme of our work involves Synthesis of different five; six and seven heterocyclic rings starting from diphenyl amine.
First part:
Step one: Reaction of diphenyl amine with chloro acetyl chloride gave α-Chloro-N,N-diphenyl acetamide(1), which was treated with hydrazine hydrate to give α-hydrazino-N, N-diphenyl acetamide(2) .The hydrazine derivative (2) was reacted with carbon disulfide in presence of KOH to give potassium-2-[2-(N,N-diphenyl amino)-2-oxoethyl]hydrazine carbodithionate(3) which was refluxed with hydrazine hydrate to give 4-amino-3-mercapto-[1H]- 1,2,4-triazin -5-yl-N,N-diphenyl amine (4).
Step two: α-(1,2-dihydro pyridiazin-3,6-dione-1-yl) N,N-diphenyl acetamide (5), α-(1,2-dihydro phthalazin-3,6-dione-1-yl) N,N-diphenyl acetamide (6) and α-(tetra hydro pyridazin-3,6-dione-1-yl)-N,N-diphenyl acetamide (7) were obtained from the reaction of α -hydrazino-N,N-diphenylacetamide (2) with maleic, phathalic and succinic anhydride, respectively .
Step three: α-[3,5-dimethyl -2[H]-Pyrazol-2-yl]-N,N-diphenyl acetamide(8) and α-[5-methyl-3-oxo-4,5-dihydro-2[H]-Pyrazol-2-yl]-N,N-diphenyl acetamide(9) were obtained from the reaction of α-hydrazino-N,N-diphenylacetamide (2) with acetyl acetone and ethyl acetoacetate , respectively.
Step four: α-[1-N-phenyl semicarbazido-4N-yl]-N, N-diphenyl acetamide (10) and α-[1-N-α-naphthyl semicarbazido-4N-yl]-N, N-diphenyl acetamide (13) were synthesized from reacting of compound (2) with phenylisocyanate and α-naphthayl isocyanate.Reaction of compound (10) and (13) with 10% NaOH produced 4-phenyl-3-hydroxy-1, 2, 4-triazin-5-yl-N, N-diphenylamine (11) and 4-α-naphthyl-3-hydroxy-1, 2, 4-triazin-5-yl-N, N-diphenylamine (14), and when compounds (10) and (13) were reacted with p-bromophenancyl bromide α-[(5-p-bromophenyl-2-hydroxy-3-phenyl-2, 3-dihydro-1, 3-oxazol-2-yl) hydrazino]-N, N-diphenyl acetamide (12) and α-[(5-p-bromophenyl-2-hydroxy-3-(α-naphthyl)-2, 3-dihydro-1, 3-oxazol-2-yl) hydrazine]-N, N-diphenyl acetamide (15) were produced .
Step five: α-(2-Arylidine-hydrazino)-N,N-diphenyl acetamide (16-21) were synthesized from the reaction of compound (2), with different aromatic aldehydes and ketones,and were used for the preparation of two types of heterocyclic derivatives.Refluxing compounds[16,17 and 21] with maleic anhydride in dry benzene for 9hrs ,produced compounds α[4,7-dioxa-2-aryl-1,3-oxazepin-3-yl-amino]-N,N-diphenyl acetamide (22-24),and refluxing compounds[16,18,19 and 20] with mercapto acetic acid in dry benzene for 10hrs produced Thiazolidin-4-one derivatives (25-28).
Step six: 3-mercapto-[1H,6H]-1,2,4-triazin-5-yl-N,N-diphenylamine (30) was obtained from the reaction of α-Chloro–N, N-diphenyl acetamide (1) with thiosemicarbazide to give α-[thiosemicarbazido-4N-yl]- N,N-diphenylacetamide (29) which suffered intramolecular cyclization when refluxed with basic media ( 2N NaOH) for 4hrs. to give triazine derivative (30).
Step seven: Treatment of α-Chloro–N, N-diphenyl acetamide (1) with thiourea gave α-( thiourea-N-yl)-N,N-diphenyl acetamide (31) which was used for the preparation of two types of heterocyclic derivatives. Refluxing (31) with conc. H2SO4 for overnight produced 2-amino-1, 3-thiazol-5-yl-N, N-diphenylamine (32) and with 2N NaOH for 3h produced 2-mercapto-[1H]-1, 3-imidazol-4-yl-N, N-diphenyl amine (33).
Second part:
This part deals with the study of antibacterial activities of some of the synthesized compounds and comparing these activities with that of the starting materials. These activities were determined in vitro using disc diffusion method against two pathogenic strains of bacteria (Escherichia Coli and Staphylococcus aurous), the results revealed that some of these compounds(2,4,12,24 and 32) showed measurable activity as shown in table (3-9).