SYNTHETICAL DRUGS 575 



Phenacetin itself (formula VI.) is a febrifuge and an analgesic 

 which is conveniently prepared by the following series of 

 operations : Para-nitrophenol (VIII.) obtained as one of the 

 products of the action of nitric acid on phenol (carbolic acid) 

 is converted by treatment with ethyl sulphate (ethylation) into 

 nitrophenetole NO2 . C6H4 . O . C2H5, and this substance is re- 

 duced to phenetidine (IX.). This base when treated in succes- 



NO. NH., N = N N =^ N 



0-0-00-00 



OH OC.Hs OC,H5 OH OCHs OC^Hj 



VHI. IX. X. XI. 



sion with nitrous acid and an alkaline solution of phenol 

 yields the complex compound (X), which is then ethylated to 

 form the substance XI. It will now be noticed that the product 

 XL is symmetrical about the dotted line, and when it is reduced 

 with tin and hydrochloric acid it splits into two parts at this 

 point, each half taking up two hydrogen atoms and giving rise 

 to a molecule of phenetidine (IX.). One molecule of phenetidine 

 is made to undergo the series of changes represented by X. 

 and XL, while the other molecule is acetylated and thus 

 converted into phenacetin (VIL). This mode of procedure is 

 adopted because of the difficulty of preparing pure paranitro- 

 phenol, and in this way an initially small amount of para- 

 nitrophenol can be made to produce a large quantity of 

 phenacetin. This drug is somewhat sparingly soluble in cold 

 water, but when the acetyl group is replaced by the lactyl group 

 CO . CH(OH). CH3 derived from lactic acid a more soluble 

 compound is produced to which the name ladophenin (formula 

 VII.) is given. This substance has an antineuralgic action ; its 

 lactyl group is more readily split off than the acetyl group 

 of phenacetin, and this change occurs under the influence 

 of the acid gastric juices, whereas phenacetin, methacctin 

 NH(CO. CH3). CfiH4. OCH3, triphenin, and other substances of this 

 series are hydrolysed only by the alkaline juices of the intestine. 

 Antipyriuc, one of the most important drugs of this group, 

 was originally discovered by Knorr in 1883 in an investigation 

 on the condensation of phenylhydrazine, CsHs.NH.NHo, and 

 ethyl acetoacetate, CH3CO . CHo. COjCoHj. These two sub- 

 stances, the former of which is an aniline derivative whilst the 



