CHEMISTRY OF THE SUPRARENAL GLANDS 85 



Synthesis of Adrenalin 



By fusing adrenalin with KOH, protocatechuic acid (Jowett) and 

 pyrocatechol have been obtained (Takamine, von Fiirth). On oxidation 

 with KMnO 4 , it yields methylamin, oxalic and formic acids (Jowett) ; 

 treatment with concentrated acids or NaOH also yields methylamin (von 

 Fiirth). After methylation with dimethyl sulphate, oxidation with 

 KMnO 4 produces veratric acid (3:4 dimethoxy benzoic acid) and tri- 

 methylamin, while the action of methyl iodid and alcoholic sodium 

 on adrenalin, by means of bisulphite, produces vanillin, so that 

 the complexes C H 3 (OH) 2 .C and NH.CH 3 (methylimid) must be 

 present in adrenalin. The latter group is in the side chain, not at- 

 tached to the benzene nucleus, because it splits off so readily. As adrenalin 

 yields tribenzoyl- and tribenzensulphon-derivatives it presumably con- 

 tains 3 hydroxyl groups, one of which is in the side chain. 



Friedmann showed that von Fiirth's compound tribenzene-sulphonyl- 

 adrenalin, which was optically active, lost its activity on oxidation to a 

 keto-compound and argued that adrenalin possessed a secondary alcohol 

 grouping. Pauly believed that the NH 2 group was of a secondary nature, 

 because adrenalin in alcoholic solution reacts with phenyl mustard oil 

 under conditions where the OH group seems indifferent so that the H was 

 in direct relation to a carbon atom. He showed that adrenalin is optically 

 active, hence contains an asymmetrical carbon atom in the side chain. 



On these data, 5 possible groupings were proposed by Pauly and of 

 these, three seemed the most acceptable. 



OH OH OH 



/\ OH /\ OH /\ OH 



II 



III 



\/ \/ \/ 



CH.OH CH 2 CH.KE.CH 3 



I I I 



CH 2 .NH.CH 3 CH.OH.NH.CH 3 CH 2 .OH 



The first is more probable, because methylation and oxidation of the 

 second compound would produce homoveratric acid (C 6 H 3 . (OH) 2 CH 2 . 

 C0 2 H:) and the third arrangement would not so readily explain the forma- 

 tion of pyrrol and of skatol. A compound with the third arrangement 

 has no pressor activity (Stolz). 



The synthesis has been carried out, first by Stolz (a), later but inde- 

 pendently by Dakin(a) (&). Stolz's synthesis is patented by Meister, Lu- 

 cius and Briining. This is the only method which is at present suitable 

 for commercial work. The method is founded on the work of Dzierzgow- 



