1911 Encyclopædia Britannica/Antipyrine
ANTIPYRINE (phenyldimethyl pyrazolone) (C11H12N2O), is prepared by the condensation of phenylhydrazine with aceto-acetic ester, the resulting phenyl methyl pyrazolone being heated with methyl iodide and methyl alcohol to 100–110° C.:—
On the large scale phenylhydrazine is dissolved in dilute sulphuric acid, the solution warmed to about 40° C. and the aceto-acetic ester added. When the reaction is complete the acid is neutralized with soda, and the phenyl methyl pyrazolone extracted with ether and distilled in vacuo. The portion distilling at about 200° C. is then methylated by means of methyl alcohol and methyl iodide at 100–110° C., the excess of methyl alcohol removed and the product obtained decolorized by sulphuric acid. The residue is treated with a warm concentrated solution of soda, and the oil which separates is removed by shaking with benzene. The benzene layer on evaporation deposits the anti-pyrine as a colourless crystalline solid which melts at 113° C. and is soluble in water. It is basic in character, and gives a red coloration on the addition of ferric chloride. In medicine anti-pyrine (“phenazonum”) has been used as an analgesic and antipyretic. The dose is 5-20 grs., but on account of its depressant action on the heart, and the toxic effects to which it occasionally gives rise, it is now but little used. It is more safely replaced by phenacetine.