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

Though Jensen’s method of synthesizing 4-acylpyrazol-5-one using conventional heating method supplanted the method used by Claisen 100 years ago⁴³, it still posed a great environmental problem⁴⁴. These methodologies, although utilized for the preparations of a variety of pyrazol-5-ones, often require the use of refluxing conditions and lengthy reaction time, ideally 2-3hrs⁴⁵. Moreover, the use of excess and often costly solvents and their recovery can pose a major environmental problem⁴⁶ especially in the large-scale synthesis. Due to the increased environmental consciousness throughout the world, extensive efforts have been developed as an alternate synthetic approach for biological and synthetically important compounds. The microwave-assisted one-pot synthesis⁴⁷ is one of the areas where substantial progress will be directed. Again, the scourge of infective diseases and increased pathogen resistance⁴⁸ by bacterial and protozoal microorganism to existing drugs and in continuation of our search for biologically active molecules has necessitated the urgent need for novel drugs⁴⁹ for treatment of Malaria and trypanosomiasis in human beings and cattle⁵⁰. These devastating effects have called for alternative, effective regimen of chemotherapy⁵¹. Moreso, environmentally hazardous pesticides and insecticides used in our farms call for benign alternatives⁵². Keeping in view of these limitations of existing drugs we synthesize acylpyrazolonates that is both efficacious and bereft of blighting of our medicinal herbs in the farms.

1.3       Objective of the study

The debilitations and health hazard caused by exposure to pathogen such as bacteria, fungi, plasmodium, and trypanosomiasis, have necessitated the synthesis of drugs that will be used for effective treatment. The specific objective of the study therefore is to: