ABSTRACT: In the present work various conventional methods and microwave method for synthesis of substituted quinolone reported. Substituted anilines were taken as a starting material and reacted with ethyl acetoacetate in presence of catalytic amount of acid and cyclized by various cyclisation agents that give the title compounds which differ in its color intensity, reaction time as well in %yield. Based on results we obtain, it has been concluded that microwave method for synthesis of substituted quinolone is more convenient in terms of reaction time and use of solvent.
In the of specific quinolines, the nitrogen-containing ring is often "closed" as a part of the synthetic process, and in some syntheses, doing so can install an hydroxyl group (an –OH ) on carbons adjacent to or across from the ring nitrogen (i.e., the C-2 and the C-4 positions, see quinoline structure above). An example of such a synthesis is the , which, depending on exact starting materials and reaction conditions, can give both 2-hydroxyquinolines (B) and 4 - hydroxyquinolines (A) as shown.
CONCLUSIONS: After performing all these relevant experiments, among the conventional methods Polyphosphoric acid is better cyclizing agent as it gives better product. It has been concluded that Microwave method is best for the synthesis of quinolone because it is less time consuming, cheap as it is solvent free and gives high yield.
As pointed out above many of the agents used in antimicrobial chemotherapy are natural or semisynthetic products and frequently single isomers are used. However, mixtures of diastereoisomers and enantiomers do occur and the remainder of this article will examine such cases using the β-lactams and quinolone derivatives as representative examples.
TABLE 2: RESULTS OF COMPARISON OF CONVENTIONAL AND MICROWAVE METHODS FOR SYNTHESIS OF 6-METHOXY 2-METHYLQUINOLIN-4(1H)-ONE
COMPARATIVE SYNTHESIS AND PHYSICOCHEMICAL CHARACTERIZATION OF SUBSTITUTED 2-METHYLQUINOLIN- 4(1H)-ONE BY VARIOUS CONVENTIONAL AND MICROWAVE METHODS
Classical methods for the synthesis of 2-methyl 4-quinolones and their derivatives 3Quinolones and their quinolinederivatives can be interconverted through oxidation and reduction reaction (Fig. A). The 2-methyl-1, 2, 3, 4-tetrahydroquinol-4-ones (R’=H) A can be transformed into the corresponding 2-methylquinolin-4(1H)-ones B with unsaturation between C2- C3 position. The latter, in turn can be converted to fully aromatic quinoline derivatives C. Several methods have been developed for the direct oxidation of system A to C.
Treatment of infectious diseases caused by pathogenic bacterial and fungal strains was one of the most traditional problems in the clinical field 9, 10. This necessity encouraged the investigators to synthesize novel and more potent inhibitory compounds (like azoles and quinolones derivatives) 11, 12 to fight them. However, the adverse effects and also appearance of bacterial or fungal resistances persuaded the investigators to study on natural products from microorganisms or herbal extracts to discover novel and safe lead compounds 9, 10.
Tetracyclines and macrolides block the protein synthesis by interfering with ribosome translation, while quinolones inhibit the replication of bacterial DNA.
Several antibiotics are commercially available for the removal of mycoplasma: BM-cyclin (Roche) contains a macrolide and a tetracycline, Ciprobay (Bayer, available only with a prescription) and MRA (ICN) are both quinolones.
The most convenient method reported to date for the synthesis of 2-methyl-4(1H)-quinolone involves the use of 2-aminoacetophenones and acetyl chloride as starting materials.
In recent years drug stereochemistry has become a significant issue for both the pharmaceutical industry and the regulatory authorities. The significance of stereoisomerism in antimicrobial agents is addressed in this review using examples drawn from the β-lactams, as being representative of semisynthetic agents, and the quinolones, as examples of synthetic agents. Within these two groups of compounds it is clear that stereochemical considerations are of significance for an understanding of concentration effect relationships, selectivity in both action and inactivation and for an appreciation of the mode of action at a molecular level.
Previously, various synthetic methodology for synthesis of 4(1H)-Quinolone has been reported by various researchers. Conrad and Limpach 1887, reported the synthetic procedure using biphenyl ether as a cyclisation agent. But the limitation of this method is long reaction time and very low yield. So various researchers have done cyclisation of initial step using different cyclisation agents to overcome the previous limitations. Gupta el al 2011, reported the synthetic methodology using Conc. H2SO4 as cyclisation agent. But again there is limitation of charring of final compound because of high reaction temperature of cyclisation step. So, overcome this limitations various researchers have reported the synthesis of 2-Alkyl-4quinolone and 2-Alkyl-4-methoxyquinoline using microwave. So it is thought of interest to develop synthetic methodology for 4(1H)-Quinolone using microwave. As per different experimental conditions results are given in below Table 1 and 2.
Unnatural 1-methyl-2-quinolone derivatives were synthesized by regioselective C–C bond formation. When 1-methyl-3,6,8-trinitro-2-quinolone (TNQ) was treated with enamines, nucleophilic addition readily occurred at the 4-position, and succeeding hydrolysis of enamine moiety followed by elimination of nitrous acid furnished 4-acylmethyl-1-methyl-6,8-dinitro-2-quinolones. The same products could be prepared by the reaction of TNQ with ketones in the presence of triethylamine. The present reaction enabled the introduction of various kinds of acylmethyl groups substituted with alkyl, aryl or hetaryl groups.