Eumotol,Byk Gulden,W. Germany,1972
ChEBI: A carbohydrazide obtained by formal condensation of one of the carboxy groups from butylmalonic acid with the hydrazino group of 1,2-diphenylhydrazine. Used (as its calcium semihydrate) for treatment of rheumatoid arthritis.
(a) A solution of 22.4 grams of dicyclohexylcarbodiimide in 120 ml of absolute
tetrahydrofuran is added dropwise at 5°-10°C in an atmosphere of nitrogen to
a solution of 20 grams of n-butylmalonic acid monoethyl ester and 19.6 grams
of freshly recrystallized hydrazobenzene in 320 ml of anhydrous
tetrahydrofuran. The mixture is then stirred for 15 hr at 25°C in an
atmosphere of nitrogen, then the precipitated dicyclohexyl urea is filtered off
and the filtrate, after the addition of 3 drops of glacial acetic acid, is
evaporated to dryness in vacuo. The residue is dissolved in 1 liter of ether, the
ethereal solution is extracted twice with 2 N potassium bicarbonate solution
and twice with 2 N hydrochloric acid, whereupon it is washed with water until
the washing water is neutral. The ethereal solution is dried over sodium
sulfate and concentrated in vacuo. The residue is fractionally distilled under
high vacuum whereupon the ester is obtained as a yellow oil. BP 170°C at
0.05 torr vacuum. Crystals which melt at 63°-65°C are obtained from
cyclohexane.
(b) A suspension of 7.1 grams of the ester obtained according to (a) in 40 ml
of aqueous 0.5 N sodium hydroxide solution is refluxed for 24 hours in an
atmosphere of nitrogen. The solution is filtered and traces of hydrazobenzene
are removed by extraction with ether. The aqueous solution is made acid to Congo paper at 10°C with concentrated hydrochloric acid, the oil which
separates is dissolved in 40 ml of ethyl acetate, the ethyl acetate solution is
isolated, and washed neutral with water. The solution is then extracted twice
with 36 ml of 0.5 N sodium bicarbonate solution each time.
The separate extracts are made acid to Congo paper with concentr
Analgesic, Antipyretic, Antirheumatic
World Health Organization (WHO)
Bumadizone, a pyrazolone derivative with antiinflammatory,
analgesic and antipyretic activity, was introduced in 1972 for the treatment of
rheumatic disorders. As it is structurally related to phenylbutazone it is subjected
to rigorously restricted indications by some national regulatory authorities. See
WHO comment for phenylbutazone.
