Synthesis and Antibacterial Evaluation of 2-( chloro / ethyl thio / seleno )-1 , 8-naphthyridine-3-azetidine Derivatives

Synthesis of new heterocyclic fuse compounds by reaction of N-acetyl-2-amino pyridine with through Vilsmeier-Haack cyclization to give 2-chloro-3-formyl-1,8-naphthyridine (1) , chloro atom changing with selenium (2) or Et-Sgroup (3) , the formyl group in the compounds (1,2,3) converted to schiff base by react with aryl amine (4-9), shiff base derivatives reaction with chloroacetylchloride in triethylamine to give azetidine ring (10-15) . The structures of synthesized compounds were confirmed by spectral and physical data. Some of the newly synthesized compounds exhibited antibacterial activity.


Experimental
Melting point were recorded on electro-thermal CIA9300 melting point apparatus and are uncorrected, 1 HNMR spectra were recorded on nucleic magnetic resinous model ultra-shield 300MHz , Bruker Co ., Germany , using TMS as internal reference and DMSO-d6 as solvent . IR spectra were recorded on Infrared Spectrophotometer Model Tensor 27, Bruker Co., Germany, by using KBr discs.
Synthesis of 2-chloro-3-formyl-1,8-Naphthyridine (1) (25) To solution of (0.01mole) of N-(pyridine-2-yl) acetamides in (0.15 mole) dry DMF with stirring POCl3 (0.06mole) at (0-5 o C) was added drop wise.The reaction mixture was heated at 80C for about 16 hrs with stirring.The reaction mixture was poured into crushed ice and the precipitated solid was filtered and washed with excess of cold water and dried and recrystallized from ethyl alcohol.The Physical Constant and chemical and spectra data of compound are given in Table 1 and 2.

Synthesis of 3-formyl-2-seleno-1,8-Naphthyridine (2) (26)
A mixture 2-chloro-3-formyl-1,8-naphthyridine (1.91 g, 1 mmol) and freshly prepared solution of sodium hydrogen selenide were taken in a round bottom flask in ethanol (20 ml).The reaction mixture was refluxed for 2-3 hrs , cooled, the reaction mixture was poured in to crushed ice and made acidified with dil (4N HCl).The product was filtered and washed with water, dried, recrystallized from alcohol.The Physical Constant and chemical and spectra data of compound are given in Table 1 and 2 .

Synthesis of 3-formyl-2-ethylthio-1,8-Naphthyridine (3) (21)
To a solution of compound (1) (1mmole) in (5 ml) dry DMF, (5ml), sodium sulphide (1.5mmole) was added and stirred for 4hrs.at room temperature, then the corresponding halo compound was added and stirred for another 1 hr.and poured in to ice-cooled water.The precipitate obtained was filtered dried and re-crystallized from ethanol.The physical constant and chemical and spectra data of compound are given in table 1 and 2 .

9) (27)
To a solution of compounds (1,2,3) (1m.mole) in ethanol (5 ml) was added with stirring aryl amine (2m.mole), and the mixture was refluxed for 4hrs.On cooling, the precipitate was formed, filtered off, washed with ethanol and cold water, dried and re-crystallized from ethanol.The physical constant and chemical and spectra data of compound are given in Table 1 and 2 .

Result and Discussion
Although many routes have been developed for functionalized 1,8-naphthyredine (28,29,30) .The Vilsmeier approach is found to be among the most efficient for achieving useful The structures of Synthysized compounds were elucidated by mean of physical data (Table 2) . the IR spectra of compound (1) showed a sharp and many absorption at 1720 cm -1 for the carbonyl of aldehydic group and absorption at 2780 cm -1 for proton of aldehydic group and absorption at 775 cm -1 for C-Cl group.
Selenium reacts quickly with sodium borohydride in aqueous solution to produce sodium hydrogen selenide vigorously and isothermally the reaction equation (17) that is:

Conclusion
We have developed a simple and efficient method for the synthesis of some new 1,8naphthyridine derivatives and organic selenium compounds and azetidine which uptake very important compounds cause the stricture of drag contain it , characterized by spectral techniques .The new synthesized compounds (10,11,12,13,14,15) were evaluated for antibacterial activities.The results obtained indicated that these compounds have a good activity against (Staphylococcus aureus and Staphylococcus epidermidis).

4 NaBH4 + 2 Se + 7 H2O → 2 NaHSe + Na2B4O7 + 14 H2
Sodium hydrogen selenide substituted chloro group in naphthyridine to selenium organic compound(2).The IR spectrum of compound (2) in Tale (2) showed absence of the characteristic absorption in IR for C-Cl bond which is present in the IR spectrum of compound (1) and presence of strong stretching absorption at 1636 cm -1 for C=Se group .The reaction of compound (1) with Na2S/DMF followed by reaction with ethyl chloride afforded a thioether derivative (3).The IR spectrum of compound (3) in Tale (1) showed absence of the characteristic absorption in IR for C-Cl bond which is present in the IR spectrum of compound (1) and presence of strong absorption at 1198-1086 cm -1 for C-S-C.The reaction of compounds (1,2,3) with aryl amine can afford schiff-base derivatives (4,5,6,7,8,9) of 1,8-Naphthyridine.The formation of compounds (4,5,6,7,8,9) was supported by absence of the characteristic absorption in IR for aldehydic group which is present in the IR spectrum of compound (1,2,3) show in table 2 .