STUDY ON REACTION OF SUBSTITUTED 4-METHYLQUINOLIN-2 ( 1 H )-ONES WITH SODIUM AZIDE

s. Reaction of different substituted 2-chloro-4-methylquinolines with sodium azide changed the direction to substituted tetrazolo[1,5-a]quinolines instead corresponding 2azido-4-methylquinolines. Required 2-chloro-derivatives were obtained from substituted 4methylquinolin-2(1H)-ones, which were synthesized by ring closing corresponding (un)substituted acetoacetanildes in the presence of ionic liquid [Bmim]OH. The structures of obtained compounds have been confirmed by using spectroscopic methods (IR, NMR and MS).


Introduction *
Quinolones present in molecular skeleton of quinolone antibiotics which are currently used in disease treatments [1], and is the most consumed antibacterial quinolone worldwide [2].Of quinolones quinolin-2(1H)-ones have been synthesized [3], but its 2-chloro derivatives did not study much jet.On the other hand, recently, the ionic liquids have been prepared and study to use in many different chemical processes [4].Herein, we report some study results about the synthesis and transformations of substituted 4-methylquinolin-2(1H)-ones from corresponding (un)substituted anilines and ethyl acetoacetate.

Experimental Section
Melting points were determined by open capillary method on STUART SMP3 instrument (BIBBY STERILIN, UK) and are uncorrected.IR spectra (KBr disc) were recorded on an Impact 410 FT-IR Spectrometer (Nicolet, USA), 1 H and 13 C NMR spectra were recorded on Avance Spectrometer AV500 (Bruker, Germany) at 500 MHz and 125.8 MHz, respectively, using DMSO-d6 as solvent and TMS as internal standard.Analytical thin-layer chromatography (TLC) was performed on silica gel 60 WF254S (Merck, Germany), 1-Butyl-3methylimidazolium hydroxide, [Bmim]OH, was prepared by our method [5].

General procedure for synthesis of substituted 4-methylquinolin-2(1H)-ones (3a-h)
To a mixture of appropriate (un)substituted anilines (1b-d, 0.1 mol), ethyl acetoacetate (15.1 ml, 0.12 mol) in 100-ml one-necked round-bottomed flask 0.2 ml of [Bmim]OH was added.After that, xylene (15 ml) was added to the reaction mixture with well shaking.A single distillation apparatus was set up and the distillation carried out slowly and carefully for about 120 minutes to remove ethanol was created in reaction.Then, the solvent xylene was removed by rotating distillation under reduced pressure.The residue, namely crude acetoacetanilides 2ad, was used directly to ring close to quinoline-2(1H)-ones 3a-d.
To the above obtained residue in 100-ml one-necked round-bottomed flask 30 ml of 70−72% H2SO4 (d=1.72 g/cm 3 ) with well stirring.Then, the reaction mixture was heated carefully on the water bath at 90°C.The smoke formed at this temperature indicated that the reaction began.After the release of smoke was diminished and the reaction mixture was no longer bubbling gas anymore, the mixture was heated at 95°C for about 30 minutes.Cooled the mixture to about 60° C and poured carefully into 300 g of crushed ice.Filter the precipitate separated, washed well with cold water to pH 7 acid, and crystallize from 96% ethanol to efford products 3a-d in form of white powder.

Conversion of quinoline-2(1H)-ones 3a-d into corresponding chloro-derivatives 4a-d
To appropriate (un)substituted 4-methylquinolin-2(1H)-one (3a or 3b-d, 0.02 mol), respectively, in 50-ml one-necked flask freshly distilled phosphoryl cloride (8 ml), shake the mixture well.Heat the reaction mixture on water at 70° C until the solid dissolved completely, then 1 h more.Cooled the reaction mixture to room temperature, and poured slowly and carefully into 300 g of crushed ice while well stirring (noted that crushed ice remained in the mixture to ensure the temperature was not over 20°C in this process), then neutralised the solution with 4M sodium hydroxide to pH 7, and allowed to stand overnight.Checked the pH of the solution, if the pH decreased, then NaOH solution needed to add in order to neutral pH is reached.Filtered the precipitate separated, carefully rinsed with cold water until neutral pH.Crystallized from 96% ethanol to yield products 4a-d as white powder.

Reaction of
To the mixture consisting of (un)substituted 2-cloro-4-methylquinolin (4a, 4b or 4f, 1 mmol) and sodium azide (1,5 mmol) in 50 ml of anhydrous DMF a few crystals of KI was added.Shaked well the reaction mixture and then heated on water bath at 75−80°C for 12 hours.The solvent was removed by distillation under reduced pressure dial.Water (about 50 ml) was added to the residue in order to dissolve inorganic salts.Precipitate separated was filtered, washed well with water, and crystallized from ethanol 96% from ethanol 96% from with activated charcoal to obtain corresponding 5-methyltetrazolo [

Results and Discussion
The transformation reaction of ethyl acetoacetat with (un)substituted anilines 1 into corresponding acetoacenilindes 2 considered completely when ethanol formed was no longer distilled.Then, the solvent was removed entirely, the residue consists mostly of acetoacetanilide used to direct ring-closure into 4-methylquinolin-2(1H)-ones 3 without isolation.We found that the use of concentrated 98% sulfuric acid was not suitable for this cyclizing reaction due no product was obtained or yields were very low.The concentration of sulfuric acid was >80% also receive the results are not satisfactory.Through a survey about influence of the concentration of sulfuric acid to obtained yields of 4-methylquinolin-2(1H)-one, we found that concentrations of sulfuric acid were 70−72% were most appropriate for the above conversion of acetoacetanilides to corresponding 4-methylquinolin-2(1H)-ones.The smaller concentrations of sulfuric acid did not promote the reaction (Scheme 1).
In IR spectra of all tetrazolo[1,5-a]quinolines 5a-f had not absorption bands in the region of 2200−2100 cm −1 of azido group.This indicated that the 2-azido compounds did not exist, but instead of the fused heterocycle, namely tetrazolo[1,5-a]quinoline.  The typical signal for all protons of the compound 5a-f appeared in 1 H NMR spectra.
Methyl group in the position 5 on the quinoline ring component had chemical shift in the upfield region at δ =~2.75 ppm (as singlet).The signals were located in the downfield region at δ=8.7−7.4 ppm belonging to 4 protons of tetrazolo [1,5-a]quinoline.Proton H-4 has a chemical shift at δ=7.96 ppm in singlet in 5a.Resonance signal of proton H-6 was downfield at δ=8.63 ppm as doublet with the coupling constant of J=8.0 Hz (Fig. 1).Chemical shift at δ=8.84 ppm belonged to proton H-9 as doublet with J=7.5 Hz.Multiplet signal in region at δ=7.99−7.98 ppm belonged to the proton H-8; Meanwhile, proton H-7 had resonance at δ=7.85 ppm as triplet with J=7.25 Hz.Amongst the protons in benzene component of quinoline ring, this proton had a resonance in the strongest field.Chemical shifts of all carbon atoms in quinoline ring located in range of δ = 148-110 ppm (Fig. 2).
In brieft, the Knorr cyclization of (un)substituted acetoacetanides have been performed by using ionic liquid [Bmim]OH as catalyst.Some substituted 4-methylquinolin-2(1H)-ones have been synthesized and converted to tetrazolo [1,5-a]quinoline via chloro derivatives.Their structure were confirmed by IR, NMR and MS methods.