3-Pyrazolones

Nowadays, only metamizole (Novalgin ) is stUl of limited relevance, as a water-soluble intravenously-applied formulation of its sodium salt for the relief of severe colic-like pain. In newer studies it could be shown that this compound 

---

Phenylhydrazine condenses with acetoacetic ester to give a pyrazolone derivative which on methylation gives phenazone. The sulphonic acid similarly gives rise to the tartrazine dyestuffs. It is used to make indole derivatives by the Fischer process. 

The preparation of methyl-phenyl-pyrazolone illustrates one of the synthetic uses of ethyl acetoacetate, as distinct from those involving the hydrolysis of substitution derivatives. 

Mix 6 2 ml. (6 4 g.) of pure ethyl acetoacetate and 5 ml. of pure phenylhydrazine in an evaporating-basin of about 75 ml. capacity, add 0 5 ml. of acetic acid and then heat the mixture on a briskly boiling water-bath (preferably in a fume-cupboard) for I hour, occasionally stirring the mixture with a short glass rod. Then allow the heavy yellow syrup to cool somewhat, add 30-40 ml. of ether, and stir the mixture vigorously the syrup may now dissolve and the solution shortly afterwards deposit the crystalline pyrazolone, or at lower temperatures the syrup may solidify directly. Note. If the laboratory has been inoculated by previous preparations, the syrup may solidify whilst still on the water-bath in this case the solid product when cold must be chipped out of the basin, and ground in a mortar with the ether.) Now filter the product at the pump, and wash the solid material thoroughly with ether. Recrystallise the product from a small quantity of a mixture of equal volumes of water and ethanol. The methyl-phenyl-pyrazolone is obtained... 

The tautomerism shown by the pyrazolones is of considerable interest. Thus the above methyl"-phenyl pyrazolone when fused or in solution can exist in the tautomeric forms (C), (D), and (E). 

When the methyl-phenyl-pyrazolone is heated with methyl iodide in methano-lie solution, it acts in the form (D), the — NH— group undergoing methy lation, with the formation of the hydriodide of 2,3-dimethyl- l-phenyl-5 Pyrazolone, or antipyrine (F), a drug used (either as the free base or as the... 

P Keto esters (t.g., ethyl ocetoacetate) are soluble in solutions of caustic alkalis but not in sodium carbonate solution. They give colours with freshly prepared ferric chloride solution a little alcohol should be added to bring the ester into solution. Sodium ethoxide solution reacts to yield sodio compounds, which usually crystallise out in the cold. Phenylhydrazine yields pyrazolones. They are hydrolysed by boiling sulphuric acid to the Corresponding ketones, which can be identified as usual (Section 111,74). 

When ethyl acetoacetate is warmed with an equivalent quantity of phenyl-hydrazine, the compound (I), which is not a true hydrazone, is first formed this undergoes ring formation (II) with loss of ethyl alcohol upon further heating. The product (II) is N or l-phenyl-3-methyl-5-pyrazolone. 

This substance may be conveniently methylated with dimethyl sulphate to 3deld 1-phenyl-2 3-dimethyl-5-pyrazolone or antipyrin (III) ... 

Merocyanines belong to the class of nonionic methine dyes combining two nuclei, one of which is a ketomethylene of acidic nature such as pyrazolone, rhodanine, oxazolone, thiohydantoin,. 

The choice of the intermediate depends on the reactivity of the ring. For a pyrazolone (34) rather than 35 is used it is the reverse for rhodanine (Schemes 52 and 53). 

These latter compounds can also be obtained by direct cyclization in a Hantzsch s reaction of the selenosemicarbazone of a /3-ketoester, that is, a l-selenocarbamoyl-3-alkyl-5-pyrazolone (Scheme 21). 

Condensation of Selenated Alkylidene or Benzylidene Hydrazones or Pyrazolones with p-nitroso Dialkyanilines... 

Hydrazono-5-(p-dialkylaminophenylimino)seienazoles, pyrazolone azomethin selenazoles, quinoid dyes, and formazans are other important dyes used in photography and the color industry (cf. previous sections). 

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. 

---