ADRENALINE (EPINEPHRIN, ADRENINE) 85 



contained 10-12 per cent, of ash. A second and a third extract, made from the mass of 

 glands with 30-40 grm. of trichloracetic acid in 5-6 litres of 60-70 percent, alcohol, yielded 

 respectively 8*57 and 3 grm. of base ; total = 35*36 grm. or 0*3 per cent, of crude product. 

 Bertrand [1904, i] extracted 600 grm. of the minced glands (of horses) with 2 litres 

 of 95 per cent, alcohol, containing 5 grm. of oxalic acid. On evaporation the extract was 

 shaken with petrol to remove lecithin, etc., and the aqueous layer was exactly precipitated 

 with neutral lead acetate and centrifuged. After removal of the excess of lead and evapora- 

 tion to 100 c.c. a slight excess of ammonia was added. 118 kilos, of fresh minced gland 

 from 3900 horses yielded 125 grm. of adrenaline. This yield is hardly more than one- 

 third of that obtained by Abel (from bullock's glands). 



The purification of the crude adrenaline may be carried out by 

 dissolving in acid and reprecipitating, but better by Abel's method 

 depending on the solubility of adrenaline oxalate in alcohol. Pauly 

 [1903] used it as follows: 12 grm. of crude adrenaline were ground 

 up with 50 c.c. of 85-90 per cent, alcohol, containing 7 grm. of oxalic 

 acid ; the inorganic impurities remain behind. After filtration and 

 dilution with 100 c.c. of water, ammonia precipitated the base in a 

 crystalline condition ; the base was freed from ammonium oxalate by 

 thoroughly washing. This process was repeated several times and 

 finally the base was washed with alcohol and ether. A more compli- 

 cated process which yielded a substance absolutely free from ash, is 

 also described by Pauly [1904]. 



Syntheses of Adrenaline. 



Adrenaline has been synthesised by several methods : 

 (i) By means of phosphorus oxychloride, catechol is condensed 

 with monochloracetic acid and the resulting chloracetocatechol (I), thus 

 first prepared by Dzierzgowski, is suspended in alcohol (50 c.c. for 100 

 grm. of the ketone). 



I II III 



CHOH 



I 

 CH 2 .NH.CH 8 



A 40 per cent, aqueous methylamine solution (200 c.c.) is then 

 added and on standing methylamino-acetocatechol separates out ; the 

 product is washed with water, alcohol and ether. The methylamino- 

 acetocatechol (II) so obtained is reduced to racemic adrenaline (III) by 

 means of aluminium amalgam, or electrolytically. The above process is 

 protected by the German patents Nos. 152814 and I 57300 of the Farb- 

 werke vorm. Meister, Lucius und Briining [1904] and appears to 



