Synthesis and Antibacterial Evaluation for Some New Schiff-bases Derived from P-aminoacetanilide

. Abstract Derivatives of Schiff-bases possess a great importance in pharmaceutical chemistry. They can be used for synthesizing different types of bioactive compounds. In this paper, derivatives of new Schiff bases have been synthesized from several serial steps. The acid (I) was synthesized from the reaction of dichloroethanoic acid with 2 moles of p-aminoacetanilide. New acid (I) converted to its ester (II) via the reaction of (I) with dimethyl sulphate in the present of anhydrous of sodium carbonate and dry acetone. Acid hydrazide (III) has been synthesized by adding 80% of hydrazine hydrate to the new ester using ethanol as a solvent. The last step included the preparation of new Schiff-bases (IV-VIII) by the reaction of acid hydrazide with appropriate aromatic aldehydes and using glacial acetic acid as a catalyst. New derivatives were diagnosed by FT-IR, and by mass and 1HNMR spectroscopy (some of them). Derivatives (IV-VIII) were screened for their antibacterial against E. Coli (G) and staph. aureus (G+). All tested compounds were found to have activity against the two kinds of bacteria.


Introduction
Schiff-bases, like aldehydes and ketones where the C=O group is replaced by azomethine group or an imine group.These compounds were prepared by the German scientist Hugo Schiff for the first time from the condensation of primary amine with aldehyde or ketone and under specific conditions, so they were called Schiff bases 1 .Suyambulingam et al synthesized Schiff bases bearing benzothiazole from reaction of 2-amino-6-methylbenzothiazole with 5bromo-2-hydroxybenzaldehyde 2 .Schiff bases have great importance and wide applications in various fields that have attracted the attention of chemists.They have the ability to produce complexes with transition metal ions 3,4 ,these complexes showed exceptional vital efficacy 5,6 .In industrial, Schiff bases have been used as corrosion inhibitors ,Charles et al synthesized new derivatives of Schiff bases with pyrrole ring shown effective in preventing corrosion of mild steel 7 .Inter alia is used in crystal engineering, catalytic reactions and most commonly in medicine field 8 .The most important medical uses include: antifungal [9][10][11] , anti-inflammatory 12 , anticancer [13][14][15] , antiviral 16 , antibacterial 17,18 , antipyretic and antimalarial 19 .This work includes new compounds of Schiff bases that were synthesized by a series of reactions starting with dichloroacetic acid and 2 moles of paminoacetanilde.The new compounds were diagnosed and their bacterial activity was studied.

Abstract
Derivatives of Schiff-bases possess a great importance in pharmaceutical chemistry.They can be used for synthesizing different types of bioactive compounds.In this paper, derivatives of new Schiff bases have been synthesized from several serial steps.The acid (I) was synthesized from the reaction of dichloroethanoic acid with 2 moles of p-aminoacetanilide.New acid (I) converted to its ester (II) via the reaction of (I) with dimethyl sulphate in the present of anhydrous of sodium carbonate and dry acetone.Acid hydrazide (III) has been synthesized by adding 80% of hydrazine hydrate to the new ester using ethanol as a solvent.The last step included the preparation of new Schiff-bases (IV-VIII) by the reaction of acid hydrazide with appropriate aromatic aldehydes and using glacial acetic acid as a catalyst.New derivatives were diagnosed by FT-IR, and by mass and 1HNMR spectroscopy (some of them).Derivatives (IV-VIII) were screened for their antibacterial against E. Coli (G-) and staph.aureus (G+).All tested compounds were found to have activity against the two kinds of bacteria.

Chemicals:
The chemicals and solvents that were used in this work were supplied by Fluka, Aldrich, BDH and Merck companies.

Techniques:
Melting points were measured by Gallen Kamp melting device.The FTIR spectra recorded by Shimadzu FTIR 8400 spectrometer, using KBr disk. 1 HNMR spectra were measured with a Bruker device (400 MHz) in DMSO-d6 solution with (Tetra Methyl Silane) as internal reference.Mass spectra measured by QP mass spectrometer, Agilent Technology (HP).

Synthesis:
New compounds were prepared by following the steps according to Scheme 1, Nomenclature of new derivatives, physical properties and percentage of products are listed in Table 1.Dichloroacetic acid (1g, 7 mmol) was dissolved in 40ml ethanol, 0.4g, 7mmol, of KOH was added, the mixture was refluxed for 1 hour then paminoaceanilide (2.33g, 15 mmol) was added.The mixture was let to refluxed for 24 hours, monitored by TLC, Rf (0.54) (benzene: ethanol, 3:2) (v/v).Subsequently, 10% of HCL was added dropwise, the precipitate was collected by filtration and washed with ethanol to give (I).All of its physical properties are listed in Table 1.
Then the residue was diluted with water and then extracted by ethyl acetate three times (340ml).The organic layer was dried over anhydrous magnesium sulfate.The solvent was evaporated to get (II) as solid.The physical properties of the prepared ester were listed in Table 1. 22e synthesized ester (II) (2g, 4.5 mmol) was dissolved in 50 ml ethanol (99%) with 0.4 ml hydrazine hydrate (80%) and let to refluxed for 24 hours (monitored by TLC).After cooling and filtration, a white precipitate of acid hydrazide (III) was obtained.All physical details were listed in Table 1. 21he appropriate aldehyde 1.3 mmol was dissolved in 40 ml of absolute ethanol, then 2-4 drops of glacial acetic acid was added to the mixture and was left to be refluxed for five minutes, then (0.5gm, 1.3 mmol) of acid hydrazide (III) was added with continued reflux for 6 hours.

Synthesis of Schiff Bases Derivatives (IV-VIII)
The colored precipitate was filtered and recrystallized from the appropriate solvent.All physical details are listed in Table 1.

Biological Activity
Compounds (IV-VIII) were dissolved at 10% DMSO and tested against two types of bacteria, Escherichia coli and Staphylococcus aurous.The experience was done by using Muller Hatton agar.On the surface of agar media microbial suspensions were spread.A stainless steel cylinder of 8mm diameter (pre -sterilized) was used to bore cavities.The plates were incubated at 37 °C for 24 hours.The zone of inhibition was measured in mm.

Results and Discussion
The new acid (I)was prepared by the reaction of 2 moles of p-amino-acetanilide with one mole of potassium dichloroacetate.The reaction was carried out according to the S N 2 mechanism, in which the two chlorine atoms were replaced by two groups of p-amino-acetanilide with loss of two molecules of hydrochloric acid, as in Scheme 1.
The FT-IR spectrum of (I) showed featured bands at 3464 cm -1 for (NH) str.group, at the range 3284-3201 cm -1 assign to hydroxyl group (str.) for acid and at 1668 cm -1 relative to acid carbonyl group as in Fig. 1.The rest of important absorption band are listed in Table 2.
The reaction of acid compound (I) with dimethyl sulphate in alkaline medium and in the presence of dry acetone gave ester derivative (II).The FTIR spectrum for new ester display absence of absorption stretching bands (OH) and (C=O) for carboxylic moiety groups with present of new bands at 1716 cm - 1 and 1257 cm -1 for (C=O) and (C-O) groups respectively, which assigned to ester moiety 20 as in Fig. 2.
Acid hydrazide (III) was synthesized by the reaction of hydrazine hydrate 80% with the ester derivative (II) in ethanal.FTIR spectrum, Fig. 3, of acid hydrazide (III) displayed stretching vibration asymmetry and symmetry at 3379 − 3197 cm −1 for (NH2-NH) and (Ar-NH) groups.Other important absorption stretching band has appeared at 1662cm -1 for the vibration of carbonyl group (amide).
Compound (III) was also characterized by mass spectroscopy and gave the set molecular weight at m z ⁄ = 370 as in Fig. 4.This supports the structural formula of both acid (I) and ester (II).
Schiff bases derivatives (IV -VIII) were synthesized by the reaction of acid hydrazide (III) with appropriate aldehydes in absolute ethanol as a solvent and few drops of glacial acetic acid.The new Schiff bases were identified by FTIR and some of them by 1 HNMR and mass spectroscopy.
Comp. (VIII) was characterized by mass spectroscopy, which gave the set molecular weight of m/z 474 Fig. 7. Scheme 2 illustrates the fragments of derivatives (VIII).The vital efficacy of Schiff bases derivatives was tested against two types of bacteria E. coli and Staphylococcus aureus.Derivatives (IV-VIII) has showed clear activity against these two types of bacteria, Table 3.

Conclusion
New derivatives of Schiff bases were prepared in this study, from the reaction of dichloroacetic acid with p-amino-acetanilide in successive steps.Most of the prepared compounds were diagnosed by FTIR, while some of them by mass and 1 HNMR spectroscopy.The biological efficacy of Schiff bases was studied, and all of them showed their effectiveness against selected bacteria.