β-Keto esters from ketones and ethyl chloroformate: a rapid, general, efficient synthesis of pyrazolones and their antimicrobial, in silico and in vitro cytotoxicity studies

نویسندگان

  • Ramasamy Venkat Ragavan
  • Kalavathi Murugan Kumar
  • Vijayaparthasarathi Vijayakumar
  • Sundaramoorthy Sarveswari
  • Sudha Ramaiah
  • Anand Anbarasu
  • Sivashanmugam Karthikeyan
  • Periyasamy Giridharan
  • Nalilu Suchetha Kumari
چکیده

BACKGROUND Pyrazolones are traditionally synthesized by the reaction of β-keto esters with hydrazine and its derivatives. There are methods to synthesize β-keto esters from esters and aldehydes, but these methods have main limitation in varying the substituents. Often, there are a number of methods such as acylation of enolates in which a chelating effect has been employed to lock the enolate anion using lithium and magnesium salts; however, these methods suffer from inconsistent yields in the case of aliphatic acylation. There are methods to synthesize β-keto esters from ketones like caboxylation of ketone enolates using carbon dioxide and carbon monoxide sources in the presence of palladium or transition metal catalysts. Currently, the most general and simple method to synthesize β-keto ester is the reaction of dimethyl or ethyl carbonate with ketone in the presence of strong bases which also requires long reaction time, use of excessive amount of reagent and inconsistent yield. These factors lead us to develop a simple method to synthesize β-keto esters by changing the base and reagent. RESULTS A series of β-keto esters were synthesized from ketones and ethyl chloroformate in the presence of base which in turn are converted to pyrazolones and then subjected to cytotoxicity studies towards various cancer cell lines and antimicrobial activity studies towards various bacterial and fungal strains. CONCLUSION The β-keto esters from ethyl chloroformate was successfully attempted, and the developed method is simple, fast and applicable to the ketones having the alkyl halogens, protecting groups like Boc and Cbz that were tolerated and proved to be useful in the synthesis of fused bicyclic and tricyclic pyrazolones efficiently using cyclic ketones. Since this method is successful for different ketones, it can be useful for the synthesis of pharmaceutically important pyrazolones also. The synthesized pyrazolones were subjected to antimicrobial, docking and cytotoxicity assay against ACHN (human renal cell carcinoma), Panc-1 (human pancreatic adenocarcinoma) and HCT-116 (human colon cancer) cell line, and lead molecules have been identified. Some of the compounds are found to have promising activity against different bacterial and fungal strains tested.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Trichloroacetic Acid as an Efficient Catalyst for One-pot Synthesis of Highly Functionalized Piperidines via multi-component Reaction

Trichloroacetic Acid (TCA) was used as an efficient catalyst for the synthesis of highly functionalized piperidines via a one-pot five-component reaction of aromatic amines, aromatic aldehydes and β-keto esters in MeOH at room temperature. The remarkable advantages offered by this method are good yields, simple procedure, short reaction times, no need to column chromatography and an easy wo...

متن کامل

ZrP2O7 nanoparticles as a robust and efficient catalyst for the synthesis of 2-aryl-5-methyl-2,3-dihydro-1H-3-pyrazolones under microwave irradiation

ZrP2O7 nanoparticles have been used as an efficient catalyst for the preparation of 2-aryl-5-methyl-2,3-dihydro-1H-3-pyrazolones by a simple one-pot four-component reaction of phenyl hydrazines, ethyl acetoacetate ,β-naphthol and benzaldehydes under microwave irradiation in good to excellent yields. When the reaction was carried out using ZrOCl2.8H2O, ZrO2 and ZrP2O7 NPs as the catalyst, the pr...

متن کامل

ZrP2O7 nanoparticles as a robust and efficient catalyst for the synthesis of 2-aryl-5-methyl-2,3-dihydro-1H-3-pyrazolones under microwave irradiation

ZrP2O7 nanoparticles have been used as an efficient catalyst for the preparation of 2-aryl-5-methyl-2,3-dihydro-1H-3-pyrazolones by a simple one-pot four-component reaction of phenyl hydrazines, ethyl acetoacetate ,β-naphthol and benzaldehydes under microwave irradiation in good to excellent yields. When the reaction was carried out using ZrOCl2.8H2O, ZrO2 and ZrP2O7 NPs as the catalyst, the pr...

متن کامل

Multicomponent preparation of highly functionalized piperidines using FeCl3.6H2O as an efficient catalyst

FeCl3.6H2O was used as an efficient catalyst for the synthesis of highly functionalized piperidines via a one-pot five-component reaction of aromatic amines, aromatic aldehydes and β-keto esters in EtOH at room temperature. The remarkable advantages offered by this method are good yields, simple procedure, short reaction times, no need to column chromatography and easy work-up. The structures o...

متن کامل

Multicomponent preparation of highly functionalized piperidines using FeCl3.6H2O as an efficient catalyst

FeCl3.6H2O was used as an efficient catalyst for the synthesis of highly functionalized piperidines via a one-pot five-component reaction of aromatic amines, aromatic aldehydes and β-keto esters in EtOH at room temperature. The remarkable advantages offered by this method are good yields, simple procedure, short reaction times, no need to column chromatography and easy work-up. The structures o...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 3  شماره 

صفحات  -

تاریخ انتشار 2013