104 Wilson and Cramer 



The results show that a short contact with boiling alcohol is without 

 effect on protagon, while prolonged treatment with warm alcohol produces a 

 (•hano-e. The product obtained after this treatment is not identical with 

 protagon, as the physical constants show, although its analytical figures 

 would agree with protagon. The results obtained by the so-called process 

 of fractional crystallisation, therefore, do not give any conclusive indication 

 as to whether protagon is a mixture or not, the method being an unsuitable 

 one, but have to be interpreted as proving the relative instability of 

 protagon towards warm alcohol. This conclusion again is not in any way 

 dependent upon either the composite or the uniform nature of protagon : 

 the products which are found after the treatment are, apart from 

 unchanged protagon, decomposition products of either the definite compound 

 protagon or of the substances constituting the mixture protagon. 



The statement made in a former paper by one of us that " protagon is 

 not decomposed by warm ether or boiling alcohol," must therefore be 

 corrected.^ In the case of boiling alcohol it is true only if the solvent 

 is prevented from acting on protagon for some time. We have not 

 investigated the effect of ether on protagon, but the instability of this 

 substance towards warm alcohol makes it probable that other solvents are 

 not without disintegrating effect. This is perhaps the explanation of the 

 contradiction above referred to, that, although protagon is not readily 

 soluble in acetone, a method of acetone extraction has been proposed for the 

 preparation of protagon. As in this method the brain material is boiled 

 with acetone for four hours, it seems doubtful, in view of our experiments, 

 whether decomposition has not taken place, and whether the substances 

 extracted are not decomposition products of protagon, possibly together 

 with some unchanged protagon. 



The relative instability of protagon towards warm alcohol is a fact 



which throws light on some obscure and controversial points of the protagon 



problem. It is clear that a prolonged treatment with warm alcohol, both in 



the preparation and in the recrystallisation of protagon, must be avoided ; 



otherwise decomposition products are formed which are extracted together 



with protagon. This is probably the explanation of the lack of uniformity 



in the composition of products obtained by some workers, especially when 



Gamgee's method has been used. It is usually stated that Gamgee's 



method was followed in every detail. We have been unable to find in 



Gamgee's communications any definite information about the time of 



recrystallisation, and most other workers who have made use of this method 



do not give any detailed statement with regard to this point. The sample 



of protagon which we prepared by Gamgee's method, slightly modified, and 



which was identical in its chemical and physical properties with protagon, 



1 While freely acknowledging this error, I wish to point out that the statement in 

 the sarne paper, that " choline is the only Imse formed " on hydrolysis by baryta water, has 

 been misunderstood by Kosenheim and Tebb. If read in connection with the paper, this 

 statement appears as the result of experiments intended to decide whether choline or 

 neurine or both bases are formed. [W. C.] 



