1,2 -Diphenyl-4- pyrazolidine-3,5-dione

Sulfinpyrazone Sulfinpyrazone, l,2-diphenyl-4,2-(phenylsulfinil)ethyl-3,5-pyrazolidine-dione (3.2.8), is an analog of phenylbutazone that is synthesized in the analogous manner of condensing hydrazobenzol with 2-(2-phenyltioethyl)malonic ester into pyrazolidinedione (3.2.7), and the subsequent oxidation of thiol ether by hydrogen peroxide in acetic acid into the sulfoxide, sulfinpyrazone (3.2.8) [70,71]. 

Synthesis Feprazone is prepared by the condensation of acetic acid 3-methyl-but-2-enyl ester with the lithium salt of 1,2-diphenyl-pyrazolidine-3,5-dione in the presence of tetrakis(triphenylphosphin)palladium in anhydrous tetra-hydrofuran. 

Phenylbutazone is 4-butyl-l, 2-diphenyl pyrazolidine 3,5-dione used as analgesic, antiinflammatory, and antipyretic drugs, and also used for the treatment of rheumatic disorder. 

In Zurich, IS cases of pseudo-lupus eiythema-todes syndrome were observed in patients treated for long periods with Venocuran . It was subsequently found that among pseudo-LE cases in Germany there were many patients who had been taking a similar product (Venopytonum). Both products contain, alongside the natural extracts, a quantity of phenopyrazone (1,2-diphenyl-3,5-pyrazolidine-dione) which may well have been responsible for this complication. The trade name Venopytonum is, however, also in use for other products in the series to which phenopyrazone has not been added (14). 

A Hammett relationship of the form ApK = 5.8am has been proposed for 4-substituted pyrazoles (74TL1609) in order to explain the effect of 4-nitro ApK = 4.5, am = 0.71) and 4-diazo groups (Apiifa = 10.0, am = 1.76). The acidity constants of a series of pyrazolidine-3,5-diones have been determined (75AJC1583) and the 4- -butyl-1,2-diphenyl derivative phenylbutazone has a pK of 4.33. 

Pyrazolidine-3,5-dione, 4,4-diethyl-1,2-dimethyl- CNMR, 5, 194 (80CB3910) Pyrazolidine-3,5-dione, 4-(dimethylaminomethylene)-1,2-diphenyl-... 

Treatment of phenylbutazone and sulfinpyrazone with one equivalent of iV-fluorobis(trifluoro-methylsulfonyl)amine (1 d) in acetic acid and chloroform solution, respectively, results in clean fluorination at position four, and the corresponding 4-butyl-4-fluoro-l, 2-diphenylpyrazolidine-3,5-dione (22a) and 4-fluoro-1,2-diphenyl-4-[2-(phenylsulfinyl)ethyl]pyrazolidine-3,5-dione (22b) are obtained in 95 and 90% isolated yield.148... 

The effect of the general toxicity of compounds on the development of oedema seems to have been completely overlooked by many workers. Winter, Risley and Nuss rightly emphasize that doses of drugs that have been used to demonstrate inhibition of oedema have often been within the toxic range. Domenjoz notes that the doses of phenylbutazone and l,2-diphenyl-4-(phenylmercaptoethyl)pyrazolidine-3,5-dione (G 25671), which suppress formalin oedema by 50 per cent, are lethal in 23 per cent of the animals. The implications of these findings must be borne in mind when interpreting the... 

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