Available on line www.jocpr.com Journal of Chemical and Pharmaceutical esearch J. Chem. Pharm. es.,, (): 1- ISS o: - Schiff s bases of piperidone derivative as microbial growth inhibitors Yatri. Shah*, Dhrubo Jyoti Sen and C Patel Department of Pharmaceutical and Medicinal Chemistry, Shri Sarvajanik Pharmacy College, Hemchandracharya orth Gujarat University, Mehsana, Gujarat, India Abstract Piperidones are a class of chemical compounds sharing the piperidone skeleton. A classic named reaction for the synthesis of piperidones is the Petrenko-Kritschenko Piperidone synthesis which involves combining a alkyl-1, -acetonedicarboxylate with benzaldehyde and an amine. This multicomponent reaction reaction related to the Hantzsch pyridine synthesis.some -piperidones give very good antimicrobial activity. So, here are some substituents of -piperidone to check whether I t give same activity or not. Introduction -Piperidinone is a derivative of piperidine with the molecular formula C H. - Piperidone is used as an intermediate in the manufacture of chemicals and pharmaceutical drugs (e.g., fentanyl)[1]. Its proven applications in Wittig eaction with Phosphorous Ylides, rganic Photoreceptor Synthesis, emoval of Sulphur Compounds from Gases, Pethidine Synthesis, Pharmaceutical Synthesis, Synthesis of Spiro Heterocycles & Fused ring Systems[]. -Phenethyl--piperidonePreparation -Phenethyl--piperidone can be prepared via a simple S substitution by reacting phenethyl bromide with -piperidinone in the presence of a phase transfer catalyst (PTC)[]. 1
Yatri. Shah et al J. Chem. Pharm. es.,, (): 1- Scheme of preparation of Phenyl ethyl -piperidone CH CH H -phenylethanamine CH =CHCCH methyl acrylate CCH CCH ame CCH methyl -((-methoxy-- oxoethyl)(phenethyl)ami no)propanoate methyl -oxo-1- phenethylpiperidin e--carboxylate H 1-phenethylpiperidin--one Procedure for reactions with different amines Phenyl ethyl -piperidone reacts with different amines [propylamine (I), isobutyl amine (II), methylamine (III)] respectively in presence of toluene as a solvent and water is removed and Schiff base is formed. Then this Schiff base undergoes reduction in presence of Zn-Hg /HCl and reduced product of Schiff base is obtained. Then it is reacted with benzoyl chloride and form benzoylated product, after benzoylation it reacts with two different azides: Hydrazide hydrate and semicarbazide.hcl and forms again Schiff base for both azides which further undergoes for clemensen reduction by reacting with ZnHg/HCl.the reduction product of both azides reacts with ethyl acetoacetate and undergoes cyclization and formed cyclized product[,].
Yatri. Shah et al J. Chem. Pharm. es.,, (): 1- General scheme for different synthesized products H reduction H 1-phenethylpiperidin--one (A) Zn/HgCl (B) CCl C H C H H reduction Zn/HgCl (D) -H H HCH. HCl (C) HH C HCH (Da) (E) CH CCH CC H reduction Zn/HgCl H HHCH (Db) H C (Ea) CH CCH CC H = CH, CH CH CH, CH CH(CH ) H C CH (Eb) Synthesized Compounds (IDb) -methyl-1-((1-phenethyl piperidin--yl)(propyl)amino-1,,dihydropyrazol--one H
Yatri. Shah et al J. Chem. Pharm. es.,, (): 1- (IEb) -methyl--oxo-1-((1-phenethyl piperidin--yl)(propyl)amino-1h-pyrazole-(h)-carboxamide H (IIDb) 1(isobutyl (1-phenethyl piperidin--yl)amino)-methyl-1,-dihydropyrazol--one H (IIEb) 1-(isobutyl(1-phenethylpiperidin--yl)amino)-metyl--oxo-1H-pyrazol-- (H)carboxamide H (IIIDb) -methyl-1-(methyl(1-phenethyl piperidin --yl)amino)-1,-dihydropyrazol--one H (IIIEb) -methyl-1-(methyl(1-phenethyl piperidin--yl)amino)--oxo-1h-pyrazol-(h)-carboxamide H
Yatri. Shah et al J. Chem. Pharm. es.,, (): 1- Physicochemical Parameters of Synthesis Compound Compound Mol.formula Mol.wt (g/mol) Polarity f a Composition C,H,(%) (cacltd.) Composition C, H, (%) (Found) PhenEthyl Piperidone C 1 H 1. Polar. C,.1;H,.;,.;,. C,.;H,.;,.;,. IDb C H. Semipolar. C,.1;H,.;,1.;,. C,.;H,.;,1.;,. IEb C 1 H 1. Semipolar. C,.;H,.11;,1.1;,. C,.;H,.1;,1.;,. IIDb C 1 H. Semipolar. IIEb C H. Semipolar. IIIDb C 1 H 1. Semipolar. IIIEb C 1 H 1. Semipolar. a-ethyl acetate: Hexane (:) Antibacterial activity C,.;H,.;,1.;,. C,.1;H,.;,1.;,.1 C,.;H,.;,1.;,. C,.;H,.1;,1.;,. C,1.;H,.;,1.;,. C,.1;H,.;,1.;,. C,.;H,.;,1.;,. C,.;H,.1;,1.;,. CMPUDS CC.(µg/ml) ZE F IHIBITI(mm) B.subtilis ±. ±. ±. (IDb) ±. ±.. ±. ±. ±. ±. ±. ±.1 ±.1 ±. ±. (IEb) ±. ±.1 ±. ±. ±.1 ±. ±. ±.1 ±. ±. ±.1 ±. (IIDb) ±. ±. ±. ±.1 ±.1 ±. ±. ±. ±. ±.1 ±. ±.
Yatri. Shah et al J. Chem. Pharm. es.,, (): 1- (IIEb) ±. ±. ±. ±. ±.1 ±. ±. ±. ±. ±. ±.1 ±. (IIIDb) ±. ±. ±. ±.1 ±.1 ±. ±. ±. ±. ±. ±. ±. (IIIEb) ±. ±. ±. ±.1 ±.1 ±. ±. ±. ±. ±.1 ±. 11±. Streptomycin 1±. 11±. 11±. 1±. 1±.1 1±. 1±.1 1±. 1±. ±. ±.1 ±. Ampicillin 11±. ±. 11±o. 1±. 1±. 1±. 1±. 1±. 1±. Histogram for Antimicrobial study of synthesized compounds Activity of Compound-IDb 1
Yatri. Shah et al J. Chem. Pharm. es.,, (): 1- Activity of Compound-IEb 1 Activity of Compound-IIDb 1 Activity of Compound-IIEb 1
Yatri. Shah et al J. Chem. Pharm. es.,, (): 1- Activity of Compound-IIIDb 1 Activity of Compound-IIIEb 1 Activity of Standard drug-streptomycin 1 1 1 1 1 1 11 11 11 1 1 1
Yatri. Shah et al J. Chem. Pharm. es.,, (): 1- Activity of standard drug Ampicillin 1 1 1 1 1 1 11 11 1 1 B.cubtilus Conclusion All the newly synthesized compounds IDb, IEb, IIDb, IIEb, IIIDb, IIIEb were screened for antimicrobial activity. The test solutions of synthesized compounds of µg/ml, µg/ml, µg/ml and µg/ml were prepared in a methanol. Streptomycin was used as standard reference drug and methanol as a control. Among the all synthesized compounds, compound IIIEb gives a better antimicrobial activity against gram positive ( and B.subtilis) and gram negative () bacteria than other synthesized compounds. H eferences [1] Mieczyslaw Makosza, Pure Appl. Chem.. (): 1. [] Cunico W, Claudia B, Ferreira MG, Capri L, Soares M, ; : 1. [] V.Boekelheide and.j.windgassen, J. Am. Chem. Soc. 1.1:1. [] T.Kitsuki and Y.Fujikura, J.rg.Chem, 1.:1. [] Petrikaite V, Tarasevicius E, Pavilonis A. ; ():. [] Pelczar MJ, Chan ES, Pelczar J, Krieg. Microbiology.th ed. London: W.B. Saunders Co. Publisher; 1.p.-. [] Chakraborty P. A Text Book of Microbiology. nd ed. Sen M. (Kolkatta): ew central book agency (P) Ltd;.p.-, -.