Synthesis of 2(1H)Pyridine and thiopyridone derivatives. Contrasting between the behavior towards electrophiles

Abstract

This thesis studies the behavior of 4-(4-chlorophenyl) 2-oxo-6-phenyl-1,2,3,4-tetrahydropyridine-3-carbonitrile (3)towards some electrophiles and nucleophiles and evaluate their antibacterial and antioxidant activities . The thesis consists of the following parts: 1- Introduction: In this section brief literatures review of the different methods of preparation and the reactions of Chalcone and 2-pyridone derivatives. 2- Results and Discussion: It deals with the discussion of the experimental methods adopted for the synthesis of the designed compounds as well as their different analytical methods applied for the characterization of the new compounds. Schemes (1-2)illustrate the synthetic pathways followed in the preparation of target compounds. In this part the author synthesis 3-(4-Chlorophenyl)-1-(3,4-dimethylphenyl)-2-propen-1-ones (1), ethylcyanoacetate, ethylacetoacetate, or diethylmalonate under Michael reaction’s condition followed by ammolysis and cyclization with ammonium acetate afforded the target compounds(3-5).

I. Behavior of 4-(4-chlorophenyl) 2-oxo-6-phenyl-1,2,3,4-tetra hydropyridine-3-carbonitrile(3)towards phosphorous pentasulphide: 1. Reaction with phosphorous pentasulphide: When 2-pyridone (3-5) and phosphorous pentasulphidewas heated under reflux for 2h in boiling dioxane. The productobtainedwasidentifiedas4-(4-chlorophenyl)-6-(3,4-dimethylphenyl)-2-3-substituted- -1,2-dihydropyridin-2-thione (6-8). 2. Reaction with ethylchloroacetate: When the 2-pyridone(3)was heated under reflux for 24h with ethylchloroacetate, the product obtained was identified as ethyl 2-(-(4-chlorophenyl)-3-cyano-6-(3,4-dimethylphenyl)-2-oxopyridn-1(H)-yl)acetate (10). 3. Reaction with acetyl chloride: The 2-pyridone(3)was heated under reflux in boiling pyridine withacetyl chloride, the productobtainedwasidentifiedas1-Acetyl-4-(4-chlorophenyl)-6-(3,4-dimethylphenyl)-2-oxo-1,2-dihydropyridine-3-carbonitrile (12)

4. Reaction with phosphorous pentachloride: When 2-pyridone(3) and phosphorous pentachloride in the presence of phosphorous oxy chloride wasrefluxed for 1h, the product obtained was identified as 2-Chloro-4-(4-chlorophenyl)-6-(3,4-dimethylphenyl)-2-oxo-pyridine-3-carbonitrile (13) . 5. Reaction with active methylene (Ethyl cyanoacetate and ethylacetoacetate): When chalcone1and ethylcyanoacetate, or ethylacetoacetate in ammonium acetate were fused25 min. in microwave, the product obtained was identified as 4-amino-5-(4-chlorophenyl)-7-(3,4-dimethyl phenyl)-2-oxo-2H-pyrano[2,3-b]pyridine-3-carbonitrile (15) and3-Acetyl-4-amino-5-(4-chlorophenyl)-7-(3,4-dimethyl phenyl)2-H-pyrano[2,3-b] pyridin-2-one (16) .On the other hand when 2-pyridone(2)fused with ethylacetoacetate or ethylcyanoacetate with amm.acetate under fusion in oil bath, it afforded the product 15 and 16 respectively

6. Reaction of 6 with ethylchloroacetate: Treatment of the thiopyridone6with ethyl chloroacetatein the presence of anhydrous potassium carbonate dissolved in boiling dioxanefor 24h, afforded the ethyl2-(4-(4-chlorophenyl)-3-cyano-6-(3,4-dimethyl) pyridine-2-ylthio)acetate (9) in good yield.

7. Reaction 16 with acetyl chloride. Equimolar of compound 16 (2.72gm) and acetylchloride(1mL) dissolved into pyridine(25mL) reflux for 2h, it afforded the acetamido derivatives 17. 8. Reaction 16 with acetyl chloride. Equimolarof compound 16 (2.72g) and phosphorus pentasulfide (4.44g) dissolved in dioxane and reflux for 2h, it afforded 4-(amino-5-(4-chlorophenyl)-7-(3,4-dimethylphenyl)-2-thioxo-2H-thiopyrano[2,3-b]pyridine-3-carbonitrile (18).

9. Reaction 16 with hydrazine hydrate Treatment of the pyranopyridone16 and hydrazine (2ml) dissolved into aq. ethanol (30ml) reflux for 2h, it affordedthe Synthesis of 5-(4-(4-chlorophenyl)-6-(3,4-dimethyl phenyl) 2-oxo-1,2-dihydropyridin-3-yl)-1H-pyrazole-4-carbohydrazide (19)) 10. Reaction 19 with hydrazine hydrate Treatment of the hydrazide19 and benzaldehyde (2ml) dissolved into aq. ethanol (30ml) reflux for 2h, it affordedthe 3-pyridinyl-4-pyrazole carbohydrazide derivative 20 11. Reaction 16 with ethylchloroacetate The 4-amino pyrano pyridine 16 was allowed to react with ethylchloro acetate in the presence of pot.carbonat and dry acetone under reflux for 15 h. It afforded ethyl 2-(5-(4-chlorophenyl)-7-(3,4-dimethylphenyl)-2-oxo-2H-pyrano[2,3-b]pyridine-4-ylaminoacetate21.

12. Reaction 16 with hydroxyl amine Treatment of the 4-amino pyrano pyridine 16 and hydroxyl amine hydrochloride in the presence dry pyridine and reflux for 2h . It afforded(E)-3-amino-2-cyano-N-hydroxy-3-(2-oxo-4,6-diphenyl-1,2-dihydropyridine-3-yl)acrylamide (22) 13. Reaction 22 with chloroacetyl chloride Treatment of the acrylamide 22 and chloro acetyl chloride in the presence dry pyridine and reflux for 5h. It afforded2-chloro-N-(5-(4-(4-chlorophenyl)-6-(3,4-dimethylphenyl)-2-oxo-1,2-dihydropyridin-3-yl)-4-cyano-3-oxo-isoxazolidin-5-yl)acetamide (23)

14. Reaction 16 with hydrazine hydrate Treatment of the 4-amino pyrano pyridine 16 with hydrazine hydrate in boiling ethanol and reflux for 3h. It afforded(E)-3-(amino(3-amino-5-oxo-1H-pyrazol-4(5H)-ylidene)methyl)-4-(4-chlorophenyl)-6-(3,4-dimethylphenyl) pyridine-2(1H)-one (24) 14. Reaction 24 with formic acid Treatment of the 1,4-diamino derivative 24with formic acid (15ml) in the presence of drops HCl and reflux for 3h, It afforded4-(4-(4-chlorophenyl)-6-(3,4-dimethyl)-2-oxo-1,2-dihydropyridin-3-yl)-2H-pyrazolo[3,4-d]pyrimidin-3(7H)-one(25) 15. Reaction 16 with benzaldehyde Treatment of the 4-amino pyrano pyridine 16 and benzaldehyde in boiling dimethylformamide (DMF) and reflux for 3h. It affordedE)-3-((((Z)-benzylidene)amino)methylene)-4-(4-chlorophenyl)-6-(3,4-dimethylphenyl)furo[2,3-b]pyridin-2(3H)-one (26) 16.Reaction 26withamm. acetate Fusion of the furo pyridine 26 with ammonium acetate for 3h.It afforded the 6-(4-(4-chlorophenyl)-6-(3,4-dimethylphenyl)-2-oxo-1,2-dihydropyridin-3-yl)-2-phenylpyrimidin-4(3H)-one (27) 17. Reaction 21 with hydrazine Treatment of the ester 21 with hydrazine hydrate in boiling aq. ethanol and reflux for 3h. It afforded (E) -2-((3-amino-5-oxo-1H-pyrazol-4(5H)-ylidene(4-(4-chlorophenyl)-6-(3,4-dimethylphenyl)2-oxo-1,2-dihydropyridin-3-yl)methylamino)acetohydraide (28)