IOSR Journal of Applied Chemistry (IOSR-JAC) e-ISSN: 2278-5736.Volume 8, Issue 4 Ver. I. (Apr. 2015), PP 21-25 www.iosrjournals.org DOI: 10.9790/5736-08412125 www.iosrjournals.org 21 |Page Synthesis and In Vitro Antimicrobial Activity of Some Novel Azaphenoxazine Carboxamide Derivatives Agbo, S. A 1* , Igbum, G. O 1 , Anoh, V. A 1 and Swande, P. I 2 1 Organic Chemistry Unit, Department of Chemistry, Benue State University Makurdi, Nigeria 2 Akperan Orshi College of Agriculture, Yandev, Gboko, Nigeria Abstract: A series of some novel azaphenoxazine carboxamide derivatives 2a – e were synthesized by coupling of 3-chloro-1-azaphenoxazine with different amides via nickel catalyzed reaction. The synthesized compounds were characterized by FT-IR, 1 H NMR, 13 C NMR and MS spectral studies. All compounds were evaluated for in vitro antibacterial and antifungal activities. The compounds 2d and 2e exhibited good antibacterial activity while compounds 2a and 2c showed good antifungal activity against tested pathogenic bacterial and fungal strains. Keywords: Azaphenoxazine, Carboxamide, Nickel(II)Chloride, Antibacterial, Antifungal I. Introduction Infectious diseases caused as a result of pathogenic bacterial and fungal infections are a serious concern to the existence of mankind and often have intricate connection to other diverse diseases when the body system fails. Thus, developing antimicrobial therapies in this regard does require a major source of research in this area. Recently, considerable focus has been deployed to developing new methodologies for the synthesis of phenoxazine building blocks. Azaphenoxazine fragment was substituted with varied synthetic reactions to develop more improved moieties with enhanced activities [4]. Specifically, phenoxazine based chemical probe with aryl substituents have been documented as potent microbial agents [4, 8, 9]. It is a veritable group of heterocycle in the field of medicinal chemistry due to their biological activities including anticancer, anti- inflammatory [3] and cytotoxic properties [10]. Several substituted phenoxazines display important biological properties like antiviral activity [10], antitumor effects [1], antibacterial [9], antifungal [2, 10] and multidrug resistance reversal activity [6]. 3-chloro-1-azaphenoxazine is an intermediate used in the preparation of azaphenoxazine carboxamide. Azaphenoxazine carboxamide contains the functional groups of phenoxazine and amide as part of its molecular scaffold. Antibacterial activity of compounds containing nature of functional fragment and substituted amides [2, 4, 9] has been reported. In the present study, some azaphenoxazine carboxamides derivatives 2a-e has been synthesized and their antimicrobial activity was determined against tested pathogenic microbial strains. II. Experimental All solvents and reagents were purchased from Sigma-Zayo Chemicals in sure-seal bottles and were used as received. Melting points were determined on a Fisher-Johns apparatus. The FT-IR spectra were recorded using KBr discs on a Shimadzu model 8400S infrared spectrophotometer. The NMR spectra were recorded on a Bruker DRX 400 spectrophotometer in DMSO at 400 MHz and 100 MHz 1 H NMR and 13 C NMR with tetramethylsilane as the internal standard. Mass spectral data were recorded on a Shimadzu LK-9000 Mass spectrophotometer. Silica gel column chromatography was performed using Merck 7734 Silica Gel (60 - 230 Mesh) and Merck-made TLC plates. Azaphenoxazine carboxamide derivatives 2a-e were prepared by the method summarized in scheme 1. The reaction of 3-chloro-1-azaphenoxazine (1) with various amides (Benzamide, formamide, urea, trichloroacetamide and nitrobenzamide) were carried out in the presence of nickel (II) chloride, triphenylphosphine ligand , potassium trioxocarbonate (iv), water and ter-butanol was heated under nitrogen atmosphere with a good yield ranging from 62 – 98 % with light yellow to brown solids. These synthesized compounds were characterized by FT-IR, 1 H NMR, 13 C NMR and MS spectral studies. PPh 3 (0.9g), NiCl 2 (0,3g) K 2 CO 3 (1.38g), t-Bu(OH) (2 mL) H 2 O (1.0 ML), 110 0 C, 4h, N 2 1 N H 2 R O 2a - e N H O N Cl N H O N NH R O Scheme 1: Synthesis of azaphenoxazine carboxamide derivatives