Heterocycles pyrazolone derivatives

Supplement to c) Pyrazolone derivatives. Derivatives of pyrazolone-(5) are important heterocyclic coupling components. They are based on the following general structure ... 

Despite the inconveniences, a certain number of studies have been carried out, particularly concerning dyes containing azomethine groups. Such as hydrazones, pyrazolones, formazans, and selenazoles quinoids. Saturated heterocycles, that is, selenazolines and selenazolidines. have also been tackled. Selenium derivatives for pharmacological or physiological applications are little developed by comparison with their thiazole homologs. 

The excellent book by the late Professor T. J. Batterham contains all the available information (up to 1973) on pyrazoles and their non-aromatic derivatives (B-73NMR165) and on indazoles (B-73NMR263). The bibliography for pyrazoles and pyrazolones has been updated in (B-76MI40402). It should be emphasized that almost all the principal results about the H NMR spectra of these heterocycles were published at that time, and thus only a summary of the principal conclusions is needed here. 

The reaction of pyrazolone bearing a /3-ketoester moiety with aliphatic dibasic functional reagents in EtOH afforded binary ring heterocycles. Whereas when using an excess of a dibasic reagent, dipyrazolo[3,4-z 3, 4 -/][l,2]di-azepine derivatives were obtained <2001SC1335>. 

Examples of five-membered heterocyclic systems having more than one heteroatom, the derivatives of which have been selected to illustrate some important methods of ring formation, are pyrazole (36), pyrazolone (37), hydan-toin (38), oxazolone (39), thiazole (40), benzimidazole (41) and benzotriazole (42). 

Monoazo dyes with heterocyclic coupling components, such as pyrazolone or pyridone, are yellow to greenish yellow. Other suitable coupling components include aniline and naphthylamine derivatives. Substituted anilines or amino-naphthalenesulfonic acids are employed as diazo components. Examples are C.I. Reactive Yellow4, C.I. Reactive Yellow 17 (see Section 3.1.5). 

R. H. Wiley and P. Wiley Pyrazolones, Pyrazolidones and Derivatives , vol. 20 in The Chemistry of Heterocyclic Compounds , ed, A. Weissberger Wiley,... 

A new variant of the Neber rearrangement has been reported recently which involves the treatment of amidoxime-O-tosylate (120) with sodium methoxide affording 2-amino-1-aziridine (121), a useful intermediate for the synthesis of a large array of heterocyclic compounds. None of possible pyrazolone (122) or cyanamide (123) derivatives were detected in the reaction mixture (Scheme 28). ° ... 

R.H. Wiley u. P. Wiley, Pyrazolones, Pyrazolidones and Derivatives in A. Weissberger, The Chemistry of Heterocyclic Compounds, Interscience Publ. John Wilkey Sons, New York London Sydney 1964. 

We have published a series of updates on the chemistry of pyrazol-3-ones, derivatives important particularly in the chemistry of pharmaceuticals and dyestuffs. Part I, which was published in 2001 in Volume 80, describes syntheses of pyrazol-3-ones. Part II (Volume 87, 2004) summarizes reactions at ring atoms at pyrazol-3-ones. Part III (Volume 95, 2008) discusses the reactivity of ring substituents of pyrazol-3-ones. Chapter 2 covers more recent syntheses and a variety of applications of pyrazol-3-ones. Together this four-part series updates the major work on pyrazolones that was published by Wiley in the series of monographs The Chemistry of Heterocyclic Compounds back in 1964. All the four parts of this mini series are authored by George Varvounis of the University of Ioannina, Greece. 

Cyclocondensation of 3-methyl-l-(5-substituted-3-phenyl-lH-indol-2-ylcarbonyl)-5-(4fi)-pyrazolones with arylidene derivatives of malononitrile using a catalytic amount of triethylamine in refluxing ethanol affords heterocycle [ ]-fused 6-amino-4-aryl-5-cyano-4H-pyrans (14JHC303). Other fused 6-amino-4-aryl derivatives arise from the three-component reaction of benzaldehydes, active methylene compounds (malononitrile/ ethyl cyanoacetate) and 1,3-dicarbonyl compounds catalyzed by 1,8-diaz-abicyclo[5.4.0]undec-7-ene (DBU) in refluxing water (14JHC618). Similar pyrazole[f)]-fused derivatives are obtained from the reaction of benzaldehydes, malonitrile, and 3-substituted-2-pyrazolin-5-ones using sodium... 

A comprehensive theoretical smdy of some pyrazolones has been presented. The predicted tautomeric equilibrium constants of these compounds were found to be in good agreement with existing experimental data, indicating that the oxo tautomers are present in aqueous solution whereas, in the main, the hydroxy tautomers predominate in the gas phase. It has been shown that, in solution, the most abundant tautomer of both l-(2, 4 -dinitrophenyl)-3-methyl-2-pyrazolin-5-one and its 1-phenyl derivative is dependent on the solvent used, while an NMR study of a number of l(2)//-dihydropyrazolo[3,4-fc]pyridin-6-ones has revealed that they all exist as 2//-tautomers both in solution and in the solid state. DFT and ab initio calculations have been carried out to investigate the stability of different tautomers of 2-hydroxy- and 2,3-dihydroxy-pyrazine in the gas phase and in different media. The data obtained indicated that 2-hydroxypyrazine is more stable than its 2-keto tautomer in the gas phase, whereas in solution the stability order is reversed. For 2,3-dihydroxypyrazine it appears that the intramolecular hydrogen-bonded hydroxyoxo and the a-diketo tautomers are the most stable species at all theoretical levels in the gas phase. Both spectroscopic and theoretical studies of the tautomerism of 2,1,3-benzothiadiazinone 2,2-dioxides and other related fused heterocyclic amides have predicted that the keto form (415) is the most abundant tautomer in the gas phase, whereas the NH hydroxy form (416) is the preferred tautomer in solution and in the solid state. 

Pyrazolone and its derivatives are an important class of heterocyclic compounds that occur in many drugs. They represent an interesting template for combinatorial and medicinal chemistry due to their simple preparation and wide biological actions including antipyretic, antibacterial, antifungal, analgesic, uricosuric, antiarthritic, antiinflammatory, antioxidant, antitubercular, and antitumor activities [64]. 

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