PHENACETIN. 37 



METHODS OF MANUFACTURE. 



The method described in the patent does not nerd to he considered 

 further. The following equations serve to illustrate the su< -r^i\ c 

 steps and the principles involved in the manufacture of phenacctin: 



6 H 4 NO 2 OH + 6H = C 6 I I , N 1 1 ,< > 1 1 + 2H,O. 

 p-nitrophenol -f nascent hydrogen = p-amid<>phenol 4- wat-r. 



C 6 H 4 NH 2 OH + C 2 H s Br = C 6 H 4 NH S OC 2 II 5 + HBr. 



( p-amidophenetol | 



])-ainidophenol -f- ethyl bromide =< or >-}- liydnhr<niir acid. 



I p-phenetidin J 



C 6 H 4 NH 2 OC 2 H 5 + CH S COOH = C 6 H 4 NHC 2 H S OOC 2 H 6 + 1 I,< >. 

 p-phenetidin -f glacial acetic acid = phenacetin + water. 



Acetic anhydrid or acetyl chlorid can be used in place of glacial 

 acetic acid. Phenacetin is obtained pure by recrystallization from 

 hot water. In 1888 J. D. Riedel rt took out a German patent for the 

 manufacture of p-amidophenetol, which is the direct antecedent of 

 phenacetin, by reducing 10 kg of diethyldioxyazobenzol with 6 kg of 

 tin and 50 kg of 20 per cent hydrochloric acid. As soon as the diethyl- 

 dioxyazobenzol is dissolved the mixture is rendered alkaline and sub- 

 mitted to distillation. Para-amidophenetol is carried over with the 

 aqueous distillate. The patentee states that this chemical is service- 

 able in preparing phenacetin. The reaction is represented by the 

 following equation: 



C 2 H 5 OC 6 H 4 NNC 6 H 4 OC 2 H 5 + 4H = 2C 2 H 5 OC 6 H 4 NH 2 . 



According to another method, 6 50 grams of chrysophenin, 100 grams 

 of zinc dust, and 250 cc of hot water are mixed in a 2-liter flask and 

 heated on a water bath with frequent agitation for one hour, then sub- 

 mitted to distillation. The p-amidophenetol is removed from the dis- 

 tillate by means of ether and the ethereal solution rendered acid with 

 30 cc of dilute hydrochloric acid, which converts the phenetol into an 

 ether insoluble hydrochlorid. The ether is drawn off and the aqueous 

 solution concentrate to crystallization. 



H. N. Morse c in 1878 treated p-amidophenol with acetic acid with 

 the expectation of getting an acetic acid salt of p-amidophenol, but 

 obtained p-acetylamidophenol. In 1894 E. Taiiber d secured letters 

 patent in Germany for a process that converts this chemical into phe- 

 nacetin. The method is as follows: Mix 150 grams of p-acetamido- 

 phenol, 165 grams of potassium ethyl sulphate, 40 grams of sodium 

 hydrate (dissolved in 500 cc of 60 per cent alcohol) in an autoclave 



D. K. Patent No. 48543, Dec. 28, 1888. 



& Bender und Erdmann, Organische Praparate, 1S94, % 1. 4M. 



Ber. d. chem. Ges., 1878, 11: 232. 



dD. R. Patent No. 85988, June 19, 1894. 



