An Efficient Approach to the Synthesis of Novel Oxazolidinones as Potential Antimicrobial Agents

Oxazolidinone, either mononuclear or condensed with other heterocyclics, has established its importance in medicinal chemistry. A variety of biological activities have been reported by oxazolidinone derivatives. e present work describes the synthesis of several oxazolidinone derivatives, 3-(2-(7-chloroquinoline-4-ylamino)ethyl)-2-imino-5-(4-chloro/nitro/methoxy benzylidene)oxazolidin-4-one 4(a–c) and 4-(2-(7-chloroquinolin-4-ylamino)ethyl)-2(4-chloro/nitro/methoxy-benzylidene)-1,6diox-4,9-di-azaspiro[4,4]nonane-3,8-dione 5(a–c). Synthesized compounds (1, 3, 4a, 5a, and 5c) were screened against bacterial strains such as S. aureus (MTCC 96) and E. coli (MTCC119) and fungal strains A. niger (MTCC 1344) and C. albicans (MTCC 871) compared with penicillin for bacteria and �uconazole for fungi as reference drugs by disk diffusion method. All synthesized compounds were identi�ed by the means of IR, NMR, and MS.


Introduction
Oxazolidinone derivatives showed very promising activities like monoamine oxidase A [1], cancer [2], HIV [3] and other interesting medicinal properties like aldose reductase inhibitors [4], metabotropic [5], and glutamate receptor antagonists [6].e chemical literature is showed that chemistry and psychopharmacological properties of these materials have the great importance in medical chemistry, and this has led to an impressive armory of synthetic routes to be developed for these compounds which have resulted in the accumulation of an enormous volume of patented literature in the last decades [7].In view of this fact, the compounds belonging to this class could be considered as interesting targets in the synthesis of compounds of medicinal interest [8].On the other hand, it is well known that oxazolidinone derivatives have a great biological relevance; these compounds carry out diverse biological functions, being present in a number of biological systems involving several biochemist reactions of physiological relevance [9][10][11].Although many methods for synthesizing oxazolidinone ring systems have been reported, they continue to receive a great deal of attention.Bacterial and fungal treatment has been a major endeavor of research and development in academic and pharmaceutical industry [12,13].Many of the available antimicrobial agents [14] exhibit undesirable side effects such as reduced bioavailability, toxicity [15], and drug resistance [16,17].erefore, the search for novel and selective antimicrobial agents is urgently required due to problems associated with currently available antibacterial and fungal drugs.
Hence the signi�cant rising research interest in the design of oxazolidinones as drugs is currently observed in the �eld of pharmaceutical chemistry.Our present study focused on the synthesis and antimicrobial activities of novel oxazolidinones having quinoline ring.

Experimental
A chemicals were purchased from Aldrich Chemical Company (�SA) and used a�er puri�cation.e progress of reactions was checked by percolated aluminum silica gel 60F 254 thin layer plates.e NMR ( 1 H) spectra were recorded at 300 MHz.NMR spectra were obtained in solutions of CDCL 3 and chemical shis reported in parts per million (ppm) and TMS as an internal standard.Melting points were determined by open capillary and uncorrected.IR spectra were recorded on FT-IR Shimadzu 8400 Spectrophotometer and reported in wave numbers cm −1 .Column chromatography was performed on silica gel (Merck).Anhydrous sodium sulfate was used as drying agent for the organic phase.(1).A mixture of 2.97 g (0.59 mol) 4,7-dichloroquinoline and 0.89 g (0.07 mole) 1-2diaminoethane was dissolved in 30 mL of distilled ethanol in 250 mL round bottomed �ask and re�uxed for 8 h.e progress of the reaction was checked by TLC, and aer completion of the reaction, the mixture was cooled and the solvent was evaporated.e solid product obtained was extracted with DCM in presence of brine solution.Organic layer was separated and dried with Na 2 SO 4 .e solvent was evaporated under reduced pressure.e solid obtained was recrystallized from EtOH (Scheme 1).

General Method for the Preparation of 2-chloro-N (2-(7-Chloroquinoline-4-ylamino)ethyl) Acetamide (2).
A mixture of compound N-(7-chloroquinoline-4-yl)ethane-1,2diamine (1) of 2.21 g (0.49 mmol) and chloroacetyl chloride of 0.75 mL (10 mmol) dissolved in triethyl amine (1 mL) and dry EtOH (25 mL) was stirred for about 30 min on ice bath then re�uxed for 4-6 hr.�rogress of the reaction was checked by TLC.Aer completion the reaction solution was cooled and the solvent was evaporated.e obtained solid product was separated with DCM and water mixture.e organic layer was �ltered and dried with Na 2 SO 4 .Resultant product was puri�ed by column chromatography in silica gel G (methanol and benzene).e eluate was concentrated, and the product was recrystallized from EtOH to give compound 2 (Scheme 1).

General Method for the Preparation of 3-(2-(7-Chloroquinoline-4-ylamino)ethyl)-2-iminooxazolid-4-one (3).
mmol) and potassium cyanate of 0.58 g (7 mmol) was dissolved in dry acetone (10 mL) and re�uxed on water bath for about 8 hr.e progress of the reaction was checked by TLC using methanol-benzene (1 : 9) ratio.Aer completion of the reaction, the reaction mixture was cooled and solvent was evaporated.e obtained solid product was neutralized by standard solution of NaHCO

Antimicrobial Activity
Five of the newly synthesized compounds were evaluated for their in vitro antibacterial activity against S. aureus (MTCC 96) and E. coli (MTCC119) and antifungal activity against A. niger (MTCC 1344) and C. albicans (MTCC 871) organisms.Disk diffusion method was used for the determination of the preliminary antibacterial and antifungal activities.Penicillin for bacteria and �uconazole for fungi were used as reference drugs.e results depicted in Tables 1 and 2 revealed that most of the tested compounds displayed variable inhibitory effects on the growth of the tested organisms.Regarding the activity of the oxazolidinone derivatives against bacteria, the results revealed that compounds 5c and 4a exhibited broad spectrum of antibacterial pro�les against the tested organisms.Regarding the activity of oxazolidinones derivative against antifungal strains the results revealed that compounds 5a and 5c revealed strong growth inhibition against the tested fungi.