THE CHEMICAL CONSTITUTION OF THE UNITS 127 



A suggested synthesis of histidine in 1909 by Gerngross from a- 

 methyl imidazole and chloral was unsuccessful. The reaction, accord- 

 ing to Windaus, proceeds in a different manner. 



Histidine, and also its natural isomer, were synthesised by Pyman 

 in 1911. By making use of Gabriel's method of synthesising the 

 glyoxaline or imidazole ring, which consists in the condensation of 

 aminoketones, R. CO. CH 2 NH 2 , with potassium thiocyanate and the 

 subsequent oxidation of the thiol group with nitric acid : 



CH NHv CH NHv 



\C.SH -- > \CH 



R _C _ N * R-C - N # 



and of Kalischer's method of preparing diaminoacetone from citric 

 acid : 



CH 2 .COOH CH 2 .COOH CH : NOH CH 9 .NH 2 



HO . C . COOH -* CO - CO -> CO 



CH 2 ,COOH CH 2 .COOH CH : NOH CH 2 .NH 



. . . , 



acetone 

 dicarboxylic acid 



di-isonitroso 

 acetone 



diamino- 

 acetone 



Pyman obtained thiol-aminomethyl glyoxaline. Nitric acid removed 

 the thiol group as sulphuric acid and at the same time the nitrous acid 

 formed in the reaction attacked the amino group replacing it by the 

 hydroxyl group and giving hydroxymethyl glyoxaline. Chloromethyl 

 glyoxaline was then prepared by the action of phosphorus penta- 

 chloride : 

 CH 2 .NH 2 CH-NHv 



do - i C ^C - N 

 CH 2 . 



NH a 



diamino 

 acetone 



aminomethyl 

 glyoxaline 



CH NH 



CH 2 . 



NH 2 



CH 



'J 



H 2 . OH 



hydroxy- 



methyl 



glyoxaline 



CH-NH 



CH 2 . Cl 

 chloro- 

 methyl 

 glyoxaline 



The chlorine atom of chloromethyl glyoxaline was easily replace- 

 able ; by exchanging it for the CN group by treatment with potassium 

 cyanide and hydrolysing the nitrile glyoxaline acetic acid (Knoop's 

 imidazole-acetic acid) was obtained ; by reducing the nitrile imidazolyl- 

 ethylamine or glyoxaline ethylamine, a base found by Barger and 

 Dale to be one of the active principles of ergot and derived from his- 

 tidine, was obtained : 



CH NH 



\ rH 

 - H' 



CH 2 .CH 2 .NH 2 



CH NH 



\CH 



C N^ 



CH 2 .CN 



CH NH\ 



1 - N> ( 

 CH 2 . COOH 



