Synthesis and Antimicrobial Activity of Azetidin-2-one Fused 2-Chloro-3-formyl Quinoline Derivatives

Azetidin-2-one fused 2-chloro-3-formyl quinolines derivatives, 3-chloro-4-(2-chloro-8/7/6methoxyquinolin-3-yl)-1-(2,4-dinitro/4-nitro phenylamino)azetidin-2-one,3-chloro-4-(2-chloro-8/7/6chloroquinolin-3-yl)-1-(2,4-dinitro/4-nitro phenylamino)azetidin-2-one, 3-chloro-4-(2-chloro-8/7/6methylquinolin-3-yl)-1-(2,4-dinitro/4-nitrophenylamino) azetidin-2-one were synthesized by four steps, respectively from N-arylacetamides, 2-chloro-3-formyl quinolines, 2,4-dinitro/4-nitro phenyl hydrazine reflux with chloroacetyl chloride and triethyl amine. However yields of quinolines having electron donating groups in all cases. The structures of the synthesized compounds have been established on the basis of physical and spectral data. The antibacterial and antifungal activity of these compounds was tested by filter paper disc method against Staphylococcus aureus (MTCC96), Escherichia coli (MTCC722) and Candida albicans (MTCC183). The results showed that azetidin-2one fused 2-chloro-3-formyl quinolines derivatives are better in inhibiting the growth of both types of organisms. Compounds AZT b2, AZT b3 to AZT g2, AZT g3 were found to be more potent compared to standard drug.


INTRODUCTION
Substituted quinolines are very simply, efficiently and conveniently synthesized in less time and high yield with less amount of raw material under mild condition with the help of Vilsmeier-Haack reagent (DMF+POCl 3 ) and substituted acetanilide.Quinoline has been posssess a wide spectrum of biological activities.Now a days quinoline derivatives are used for a convenient starting material of various further substituted quinoline.
Formylation of heterocyclic compounds 1 , may be achieved by heating heterocyclic compound with Vilsmeier reagent i.e (DMF+POCl 3 ) phosphorous oxychloride and dimethyl formamide, the intermediate is hydrolysed in the presence of mild base give 2-(ortho)-substituted heterocyclic compound 2 .This reaction is known as Vilsmeier-Haack reaction.The treatment of infectious diseases still remains an important and challenging problem.The search of novel antimicrobial agents is a field of current and growing interest.Many compounds have been synthesized with this aim; their clinical use has been limited by their relatively high risk of toxicity, bacterial resistance and/or pharmacokinetic deficiencies [3][4] .According to the literature, pyrazoloquinoline and triazolo-thiadiazole quinoline derivatives are reported to possess various biological activities such as antibacterial 5 , antifungal 6 anti-inflammatory 7 .As a part of our continuing interest, we have investigated for the first time cyclic azetidin-2-one fused 2-chloro-3-formyl quinoline derivatives with an aryl hydrazine group.

METHODS AND MATERIALS
All chemicals were used of analytical grade from Chemdyes Corporation (Chemco) limited.All melting points were taken in open capillaries tube and are an correct.The progress of all reaction of the synthesized compound was monitored by TLC i.e (Thin layer chromatography).TLC was run using silica gel PF 254, 366 as an adsorbent and ethyl acetate -n-hexane in different ratio as eluent.Spot were visualized using solid fumes, by keeping of TLC plate in iodine chamber.Step I Step I

REACTION
Step Experimental Procedure for IR spectra were recorded on a FT-IR (Bruker) spectrophotometer, 1 HNMR Bruker Avance II 400 MHz instrument using DMSO as solvent and TMS as internal reference (Chemical shift in ä, ppm).The following abbreviations were used to indicate the position of functional groups in term of stretching and bending (FT-IR), peak multiplicity s-singlet, d-doublet, t-triplet, q-quartet, m-multiplet, dd-doublet of doublet ( 1 HNMR).
Step I Preparation of ortho substituted acetanilide 8,9 Aniline (5 ml) is dissolved in hydrochloric acid (4.6 ml concentrated hydrochloric acid and 12.5ml water) in a beaker.To the clear solution are added acetic anhydride (6.5 ml).The mixture is stirred until acetic anhydride has completely reacted.The mixture are immediately poured in to a solution of sodium acetate (8.3 gm) in water (25 ml).The solution is stirred and cooled in ice.The separated acetanilide is filtered.It is recrystallized from boiling water (100-125 ml) to which ethyl alcohol has been added (Table 1).
Step II Preparation of 2-chloro-3-formylquinoline CFQ 8,9 To a s o l u t i o n o f a c e t a n i l i d e (N-phenylacetamide) (5 mmoles) in dry DMF (15 mmoles) at 0-5 o C POCl 3 (60 mmoles) was added dropwise with stirring and the mixture was then stirred at 80 -100 o C for time ranging between 4-16 hr.The mixture was poured on to crush ice, stirred for 5 minutes and the resulting solid filtered, washed well with water and dried.The compounds were recrystallized from ethyl acetate.Phosphoryl chloride (commonly called phosphorus oxychloride) is a colorless liquid with the formula POCl 3 .It hydrolyses in moist air to phosphoric acid to release choking fumes of hydrogen chloride.It is manufactured industrially on a large scale from phosphorus trichloride and oxygen or phosphorus pentoxide.It is mainly used to make phospha (Table 1).

Table 2 : Antimicrobial activities of Compounds AZT b2-AZT g3 (Diameter of the zone of inhibition in mm)
* The solvent (control) is Dimethy formamide 1. Staphylococcus aureus reference compound Amikacin 2. Escherichia coli reference compound Amikacin 3. Candida albicans reference compound Ketoconazole