86 ALBEKT C. CRAWFORD 



ski, which showed that if pyrocatechol is heated with chloracetyl chlorid, 

 chloracetylpyrocatechol is formed. When this compound is condensed 

 with methylamin, and the resulting methylamin-acetyl-pyrocatechol is re- 

 duced with aluminum amalgam, or electrolytically, an amino alcohol is 

 obtained which answers the demands of the first formula and which has 

 many of the qualities of adrenalin, but is optically inactive. 



HO A / ^ 



1 N__/ +CH..C1 =HO <^ ^> C.CH 2 .C1- 



Cl O 



HO 



TTO / \. 



, C.CH 2 .C1 + 2NH 2 .CH 3 = HO <^ ^ C . CH 2 .NHCH 3 -f NH 2 CH 3 HC1 

 / O O 



HO HO 



H \ X C - CH2 - NH - CH3 - H2==HO \ \CH.OH.CH 2 NH.CH 3 



O 



One trouble with this synthesis is that the NH 2 group is easily split 

 off (Stolz (&)'). 



Other synthetic methods have been proposed, i.e., methylating the 

 base 3 :4 di-hydroxy-phenylethanolamin or arterenol. The latter may be 

 made by reducing aiiiino-aceto-pyrocatechol or by reducing the cyanhydrin 

 of protocatechuic aldehyd. 



The methylene and dimethyl ethers of adrenalin have been synthe- 

 sized, but these cannot yet be directly converted into adrenalin (Barger and 

 Jowett; Barger; Barger and Ewins(&) ; Tutin, Tat on and Hann; Man- 

 nicb ; Paulv(r) ; Pauly and Xeukam; Bottcher). 



Recently N"agai has patented a method for the manufacture of 

 adrenalin by condensing protocatechuic aldehyd with nitromethane in the 

 presence of weak inorganic or organic bases, which he does not specify, 

 and then reducing the resulting di-acetyl-di-hydro-phenyl-nitro-ethanol 

 with Zn dust and acetic acid, in the presence of formaldehyd. The di- 

 m-el vl adrenalin, when hydrolyzed by HC1, gives adrenalin hydrochlorid. 



The study of the synthesis of adrenalin has attracted attention to 

 two other synthetic compounds homorenon or w-ethylamino 3 :4 di- 

 hydroxy-acetophenon (()H) 2 C f; H,.CO.CH,> T HC 2 H r) and epinin or 3:4 

 dihydroxy-phenylethyl methylamin (OH) 2 C r( H,CH 2 CH,NH.CH: 3 . Hom- 

 oreii(;n exerts a pressor action about like natural adrenalin, while epinin 

 is about % as active. 



A number of other pyrocatechol derivatives exert a pressor action 

 and several have been used commercially; thus methylamino-acetylcatechol 



