SYNTHESIS, CHARACTERIZATION AND PHARMACOLOGICAL STUDIES OF 4-ACYLPYRAZOLONE COMPLEXES OF SOME D-BLOCK ELEMENTS

CHAPTER ONE

1.0       Introduction

Investigation on 4-acyl-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (4-acylpyrazol-5-one) and its transition metal complexes has attracted significant attention because of their applications as extractants¹, antipyretic², analgesic³, antitubercular⁴, antimycobacterial⁵, antibacterial⁶, antifungal⁷, and antineoplastic⁸ drugs. 4-acylpyrazol-5-one, is an enolizable ligand with strong ligating ability. These ligands are synthesized by direct acylation at C – 4 of 3-methyl-1-phenyl-1H-pyrazol (4H)-5-one (PMP) with acyl chloride or anhydrous pyridine in dioxane at reflux⁹. 4-acylpyrazol-5-ones are phototropic isomers forming ketoenol, diketo-, and aminodiketo tautomers¹⁰. These features of tautomerism imbues them with several coordination modes¹¹ (O, O-donors, O, N-donors, O-donor) and easily form coordination compounds with virtually all the elements in the periodic tables. This ligating ability is more predominant with transition elements because of increased bonding orientation associated with the d-orbitals. Owing to their high extracting ability, lower pKa values (in comparison with acetylacetone, (acac^–), and thenoyltrifluroacetone, (HTTA), great separation power, intense colour of complex extract, and low solubility in aqueous medium, several workers have used 4-acylpyrazol-5-ones to extract metal ions¹². Based on their ligating properties they are also used in the spectrophotometric determinations of several metal ions such as Fe(III)¹³, V(VI)¹⁴ UO₂²⁺¹⁵ Mo(IV)¹⁶, Ni(II)¹⁷, Co(II)¹⁸, Mn(II)¹⁹, V(IV)²⁰, Cr(VI)²¹, Ca(II)²², Zn(II)²³, Mg(II)²⁴. 4-acylpyrazol-5-ones such as acetyl-(HPMAP), propionyl-(PMPrP), Butyryl-(HpmBuP), isobutyryl-(Iso-HPMBuP), benzoyl (HPMBP), valeroyl (HPMVP), isovaleroyl- (HPMisoVP), caproyl (HPMCP) trifluoroacetyl (HPTFP), and trichloroacetyl-(HPTCP)²⁵ have been synthesized, spectroscopically characterized, and used in diverse applications that cut across medicine²⁶, biology²⁷ and pharmacology²⁸.

Because of their thermal stability²⁹ these functionalized ß–diketones are used as molecular precursors in chemical vapour deposition techniques and in fabrication of polymer light-emitting diodes for low-cost, full-colour, flat-panel displays³⁰. The magnetic and electronic properties of ß-dikotonates are also used in liquid crystals display and supramolecular assemblies³¹. As catalysts in hydroformylation and hydroboration, 4-acylpyrazolonates are used as spectator donors³² for intermediate species in organic reactions. Investigation of coordination compounds of lanthanide ions has been done by several worker owing to their fluorescent broad applications in biochemistry³³, materials science³⁴, and medicine³⁵. 4-acylpyrazol-5-ones with a pyrazole nucleus share structural features with some pyrazol-5-ones derivatives (metamidozole, phenazone or antipyrine, dipyrone, edaravone) that exhibit as analgesic, antipyretic and anti-inflamatory activity³⁶. Because of its promising antipyretic and analgesic activity, these drugs are used for treating fever and flu-like infections³⁷. Edarovone (3-methyl-1-phenyl-2-pyrazolin-5-one) which has close resemblance to 4-acyl-pyrazol-5-one is used in the treatment of brain ischemia³⁸ and myocardial ischemia³⁹. Also, because of pyrazole functionality, 4-acyl pyrazolone exhibit cytoxic activity against bacterial⁴⁰ and fungal pathogens⁴¹ and cancer cells⁴².

1.2       Statement of the problem