Resolution of phyto-hormone acids 



generally used and, in fact, all the optically active acids so far produced have 

 been made by this method. 



The range of active bases available is not very large, comprising first the 

 naturally occurring alkaloids mainly from the quinine, morphine, and 

 strychnine groups. All of these are tertiary amines and are readily available. 

 A somewhat rarer alkaloid, yohimbine, which is a secondary amine has been 

 useful in one or two instances. A later development is the use by Matell 

 (1953) of two synthetic optically active primary amines, phenylethylamine 

 and phenyl/jopropylamine. Both of these can be obtained in( + ) and ( — ) 

 forms, the ( — ) form of the latter being a by-product of the manufacture of 

 fl'f.v/ro-amphetamine, a widely used sympathomimetic drug. 



In our first work on the resolutions of a-(2:4-dichlorophenoxy)propionic 

 acid, following the above procedure, we got very poor results with the 

 alkaloids which were then available and using dextro-a.mphet'dmme: we also 

 could not get a crystalline salt. This was later confirmed by Matell (1953). 



However, it occurred to us that since organic salts of primary amines 

 usually lose water on heating to form substituted amides, we might find 

 that these amides could be more readily separated into their optical com- 

 ponents than the too soluble salts themselves. 



Using in this way ( + ) amphetamine and racemic a-(2:4-dichlorophenoxy)- 

 propionic acid and heating a molecular mixture of these to about 170°C 

 until one molecule of water was eliminated, the melt then being diluted with 

 methanol, we obtained a crystalline mass of the compound, later identified as 



CHn 



CH, 



CI 



O— CH— CO— NH^CH— CH, 



( + ) 



( + ) 



:m.p. 164-5°; [a] ^^- 39-5 



(c=2-00-in toluene)), 



CI 



the compound 



CH, 



CI 



O— CH— CO— NH— CH— CH, 



CH, 



(-) 



CI 



( + ) 



[m.p. 106-7°; [a]f)' + 31-7 



(c^ 1-5 in toluene)) 



remaining for the most part in solution. 



The (+)-(+) amphetamide is readily purified completely by one or two 

 recrystallizations and is then optically pure. 



Its constitution was definitely established by hydrolysis, giving one mole- 

 cule each of ( + ) a-(2:4-dichlorophenoxy)propionic acid and ( + ) amphet- 

 amine. Neither the acid nor the base was racemized in this hydrolysis. 



213 



15 



