Synthesis and Biological Activity of Some 2-( 2 ’-( Substituted Phenyl-4-thiazolidinone-3-yl )-1 ’ 3 ’-isoxazol-4-yl ) aminoquinoline Derivatives

Quinoline a heterocyclic nucleus, played a pivotal role in the development of different medicinal agents and in the field of agrochemicals. Several 2-(2’-substituted phenyl-4-thiazolidinon-3-yl)-1’3’-isoxazol-4-yl) amino-quinoline IV(a-k) have been prepared 2-(substituted arylideneimino1’3’-isoxazol-4’-yl) aminoquinoline III(a-k) and tested for their antimicrobial and antifungal activity against different microorganism. The structure of compound III(a-k) and IV(a-k) have confirmed on the basis of their elemental and spectral analysis such as IR, H NMR and Mass spectrometry.


Introduction
The chemistry of quinoline has gained increasing attention due to its various diverse pharmacological activities [1][2][3] .Numerous quinoline, derivatives have been prepared and their pharmacological properties were evaluated.Many of these compounds have proved to be active anticancer [4][5] , anti-inflammatory 6 antiallergic 7 and antimicrobials [8][9][10][11] antimaralial 12 agent.Further, the utility of quinoline derivatives in the preparation of some dyes and pigment have been reported 13 .On the other hand isoxazole derivatives controlled Botrytis cinera on cucumbers have been found to have antiviral properties against herpes type II virus 14 .Penicilline derivatives containing isoxazole ring are found to be antibacterial activities.Isoxazole derivatives 15 are used as corrosion inhibitors for fuels and lubricants 16 .Moreover thiazolidinones have a broad spectrum of pharmacological properties i.e. antibacterial 17 , antifungal 18 and antiinflammatory 19 .

Experimental
The melting points were determined in open capillaries with an electrothermal melting point apparatus and are uncorrected.IR spectra were recorded on a simadz FT-IR-8400 spectrometer and 1 H NMR spectra on Bruker spectrometer (300 M Z ) using TMS as an internal standard.All chemical shift values were recorded as δ (ppm).

Synthesis of 2-(chloroacetyl)aminoquinoline (I)
Chloroacetyl chloride (0.02 mole) was added to a solution of 2-aminoquinoline (0.02 mole) in dry benzene (80 mL) at 0-5 0 C. The reaction mixture was stirred for 4 h at 45 0 C. Excess of benzene was distilled off.The solid thus obtained was washed with petroleum ether and kept in refrigerator overnight and solid obtained was purified by recrystallization from benzene to yield compound I, m.p.189 0 C, yield 96%.

Synthesis of 2-(substitutedarylideneimino-1'3'-isoxazol-4'-yl)aminoquinoline(IIIa-k)
To a solution of compound II (0.02 mole) in ethanol (60 mL), substituted aromatic aldehydes (a-k), (0.02 mole) and a few drops glacial acetic acid were added and the mixture refluxed for 10 h.It was then cooled, concentrated and poured into crushed ice and filtered.The product thus obtained was purified by recryatallization from methanol to get compound III(a-k).The related physical data are given in Table 1.

Results and Discussion
The reaction of chloroacetyl chloride and 2-amino quinoline in dry benzene gave 2-(chloroacetyl) amino quinoline I.The structure of I was confirmed from its spectral data and analytical studies.The compound II was obtained by reaction of I with urea in acetone and well characterized using its spectral and analytical data.Its IR spectrum revealed the presence of NH 2 group by exhibiting a strong absorption at 3442 cm-1 and the formation of isoxazole ring was confirmed by the absence of C=O str at 1826 cm -1 .The NMR spectrum of II in CDCl 3 show one singlet at 8.6 δ due to NH 2 protons and one singlet at 5.7 δ due to NH proton.The two complex multipletes at 6.2 δ & 4.2 δ was assigned for five aromatic protons.The C, H, N, analysis of the compound II was in good agreement with the proposed molecular formula C 12 H 9 N 3 O .The reaction of II with substituted aromatic aldehyde and few drops of glacial acetic acid gave III(a-k) and was well characterized using its spectral and analytical data.Its IR spectra revealed the presence of C=N group by exhibiting a strong absorption at 1683 cm -1 the NMR spectrum of III(a-k) in CDCl 3 show two complex multiplets at δ 6.9 & 6.1 was assigned for seven aromatic protons.Further the reaction of III(a-k) with thioglycolic acid in the presence of acetic acid was carried out with an interest that the reaction would proceed as shown in Scheme 1 and at the end, this attempt yield IV(a-k).The IR spectrum of IV(a-k) shown strong absorption at 1838 cm -1 due to >C=O group.The NMR spectrum exhibited two singlets at 3.8 & 4.2 for C 2-H 2 and C 5 -H protons of thiazolidinone ring.Three unsymmetrical multiplets appear in 7.3 δ, 6.0 δ, 6.2 δ with eleven aromatic protons.This was also supported by the mass spectrum of the compound which displayed the molecular ion peak at 480.51.The elemental analysis was also in good agreement with the molecular formula C 27 H 20 N 4 O 3 S.All compounds show good to moderate biological activity.

Antimicrobial activity of synthesized quinoline derivatives
Several workers determined antimicrobial activity in vitro using: a).Turbimetric method b).Serial dilution tube technique.c).Diffusion methods.
In the present study the filter paper disc diffusion plate method was employed to evaluate the antimicrobial activity in vitro.Filter paper disc diffusion plate method 16 was used.The medium was first inoculated with a loopful of broth culture of the organism and shaken for uniform distribution.It was poured into Petri dish.Discs soaked in test sample solution were placed over the seeded medium and pressed so that all parts of disc come in contact with the medium.The seeded plates were incubated at 28 0 C for 32 h in case of bacteria and 37 0 C for 72 h in case of fungi.Same procedure was adopted for standard drugs.The activity was determined by using 4% and 2% solution of synthesized isoxazole, thiazolidinone derivatives.4% and 2% solutions of the standard drugs, streptomycine and tetracycline (for bacteria) and nastytine, amphotericine-B (For fungi) were also prepared.Related data have been given in Table 3 -6.

Insecticidal activity of synthesized quinoline derivatives
Cockroaches were selected for the study.4% (w/v) solution of synthesized compounds of isoxazole, thiazolidinone was prepared in acetone.4% (w/v) of solution of synthesized compounds was injected into the abdominal region of the cockroach with the help of micro syringe.The time of death, the antennae becomes motionless, the appendages shrunk and folded towards the ventral side and cockroach lay dorsally.For each sample, four replications were performed and average KD value noted.Cypermethrin 25% EC was used as standard.Its 4% (w/v) solution was prepared in acetone.It belongs to pyrethroid group.Related graphs are given in Figure 1 &

Table 1 .
Physical characterization data of synthesized compounds III

Table 4 .
Antifungal activity of the synthesized III

Table 5 .
Antibacterial activity of the synthesized IV(a-k) against various bacteria at two different concentrations (ppm)

Table 6 .
Antifungal activity of the synthesized IV(a-k) against various fungi at two different concentrations (ppm)