Synthesis and Evaluation Antibacterial Activity of Some New Substituted 5-Bromoisatin Containing Five, Six Heterocyclic Ring

: This research includes the synthesis of some new different heterocyclic derivatives of 5-Bromoisatin. New sulfonylamide, diazine, oxazole, thiazole and 1,2,3-triazole derivatives of 5-Bromoisatin have been synthesized. The synthesis process started by the reaction of 5-Bromoisatin with different reagents to obtain schiff bases of 5-Bromoisatin intermediate compounds(1, 8, 19) by using glacial acetic acid as a catalyst in three routes. The first route, 5-Bromoisatin reacted with p - aminosulfonylchloride to product compound(1), then converted to sulfonyl amide derivatives(2-7) by the reaction of compound(1) with different substituted primary aromatic amine in absolute ethanol. The second route includes the reaction of 5-Bromoisatin reacted with ethyl glycinate to give 5-bromo-3-(Ethyl imino acetate)-2- oxo indole(8), which undergo react with hydrazine hydrate 80% to obtain hydrazine derivatives(9) that react with different acid anhydrides to obtain diazine derivatives(10-14). Also compound(8) reacts with urea and thiourea to give compounds(15,16) which undergo cyclization with p -bromophenacylbromide in absolute ethanol as a solvent to obtain oxazole (17) and thiazole (18), respectively. The third route included the reaction of 5-Bromoisatin with p -phenylenediamine in ethanol to obtain compound(19) which is converted to new substitutes 1,2,3-triazole derivatives(22,23) by diazotation of compound(19) and treating the resulted salt(20) with sodium azid, then acetylaceton or ethylacetoacetate, respectively. Newly synthesized compounds were identified by spectral methods. (FTIR, 1 H-NMR, 13 C-NMR) and measurements of some of its physical properties and also some specific reactions. Furthermore the effects of the synthesized compounds were studied on some strains of bacteria .


Introduction
Isatin and its derivatives have a broad range of important biological, pharmacological and medicinal properties.It has discontinuous and The 2 nd National Conference of Chemistry 543 distinct distribution of peripheral tissue and body fluid and isatin conjoint site that are widely distributed and widely used as starting materials for the synthesis of broad range of heterocyclic compounds and as substrates for drug synthesis [1][2][3].Sulfonamides are one of the oldest groups of the drugs; they have been in clinical use for over 70 years.It plays an important role in medicinal chemistry and it is used as anticancer drugs because it contains the sulfonamide subunit [4].Owing to its wide application as,antimicrobial [5], antibacterial [6], antioxidant [7], anticonvulsant, antipsychotic, antihypertensive, anti-inflammatory, diuretic, hypo-glycemic [8][9][10].Sulfonamides are an essential class of antibacterial drugs used in medicine and veterinary practice [11].Sulfa drugs are widely used in the treatment of infections, especially for patients intolerant to antibiotics.The vast commercial success of these medicinal agents has made the chemistry of sulfonamides become important in pharmaceutical sciences [12].Pyridazine nucleus has been extensively studied as new and selective medicinal agents and as drugs acting on the system of cardiovascular; its derivatives can be used in the prostate cancer [13].The biological activities of Its derivatives are antibacterial [14], antimicrobial [15], antifungal [16], antiinflammato-ry activities [17]antimala, analgesic and antipyretic [18].Also developed newly pyridazine derivatives for the treatment of chronic lower back pain, chromic inflammatory pain associated with csteo arthritis and rheumatoid arthritis [19].Oxazole and its derivatives used in industrial purposes and increased interest in their application of chemistry [20].Thiazole derivatives are used as sedative, cardiotonic, anesthetic and many other applications of thiazole derivatives like cosmetics (sunscreens) or in liquid crystals [21].1,2,3-Triazoles are mainly useful in synthetic organic chemistry due to their variety of interesting biological activities like antibacterial, anticancer, antiviral,analgesic, fungicidal activity [22].Triazoles have also a wide variety of interesting drugs [23].

Materials and Instruments
Chemicals used in this work are supplied from BDH, Fluka, Merck and Sigma Aldrich companies and used without further purification.Melting points were uncorrected and registered via digital Stuart scientific SMP3 melting point device .Thin layer chromatography (TLC) used to check purity and homogeneity of synthesis compounds.FTIR spectra of the compounds in the (4000-600) cm -1 spectral range were recorded on SHIMAZU FTIR-8400 Fourier transform Infrared spectrophotometer using KBr discs. 1 HNMR and 13 CNMR spectra were recorded on Bruker 600MHz in Germany, instrument using TMS as internal reference and DMSOd 6 as a solvent.

Synthesis of 5-bromo-3-[p-imino( phenylenesulfonyl subutituted amine)]-2-oxo indole(2-7)[25]
substituted primary aromatic amines (0.0025mol) are dissolved in ( 7 ml ) absolute ethanol, place this solution in 50 ml round bottomed flask then (1g, 0.0025 mol.) of compound (1) was added in partition with stirring and trying to keep the temperature below 40°C.The mixture was refluxed for (3 hrs.) with continuous stirring after that the mixture was cooled to room temperature and poured into excess cold water with stirring; the obtained precipitate was filtered, washed with water for several times and dried.The product was purified by recrystallization from methanol.Physical properties and FTIR spectral data of the products are listed in Table (1).

Anti-bactrial activity test[28]
The test was performed according to the disk diffusion method.Some of the synthesized compounds were tested against two strain -ve bacteria (Escherichia coli and pseudoman acruginosa) and two strain gram +ve (Bacilles and Staphylococcus aura).Whattman no.1, 5mm diameter of filter paper disk were sterilized via autoclaving for 15 min.at 121°C.The sterile disks were impregnated with different compounds (800µg /disk).Agar plates were surface inoculated uniformly in 100°µL from both culture of tested microorganism.The impregnated disk was placed on the medium suitably spaced a part and the plates incubated at 5 °C for 1 hr. to permit good diffusion ,then transferred to an incubator at 37°C for 24 hrs. .The inhibition zones caused by various compounds on the microorganisms were examined.

Physical Properties
Major FTIR Absorption cm

Conclusion:
The present research involves the synthesis of sulfonylamide, diazine, oxazole, thiazole and 1,2,3-triazole derivatives of 5-Bromoisatin to explore their antibacterial activity.Exhibited highest antibacterial activity for staphylococcus aureus compound (19), Bacilliessubtilus compound(8), Escherichia coli compound (15) and Pseudomonas aeruginosa compound (1,23).Hence, it is conculuded that there is in ample scope for further study in developing these as good lead compounds for the treatment of bacterial strain as well as fungal strain.