40 THE CHEMICAL CONSTITUTION OF THE PROTEINS 



The condensation of benzaldehyde and hippuric acid, and the 

 formation of phenylalanine by the action of ammonia had been pre- 

 viously carried out by Plochl in 1884, but he was unable to explain the 

 various stages which took place. 



E. Fischer has synthesised phenylalanine by the action of ammonia 

 upon the corresponding halogen fatty acid, which he prepares from 

 malonic ester and benzylchloride. There are six stages in the complete 

 process, as follows : 



COOC 2 H 5 

 CH 2 



Na 



COOC 2 H 5 

 Malonic ester 



COOH 

 CH.CH 2 C 6 H 5 - 



COOH 



Benzylmalonic acid 



COOC 2 H 5 

 > CHNa 



COOC 2 H 5 

 Sodiummalonic 

 ester 



C 6 H 5 CH 2 C1 



COOCH 



KOH 



Br 



COOH 



~> C(Br) . CH 2 C 6 H 5 - 



COOH 

 Benzylbromomalonic ester 



CH . CHrjCgHg 



COOC 2 H 5 



Benzylmalonic ester 



H 

 > C(Br).CH 2 C 6 H 5 - 



COOH 



Benzylbromacetic acid or 

 phenyl-o-bromopropionic acid 



NH, 



C 6 H 5 . CH 2 . CH(NH 2 )COOH 

 Phenyl-a-aminopropionic acid 



By this means large amounts of phenylalanine can be prepared, 

 and have been employed in studying the derivatives of phenylalanine 

 and in the synthesis of polypeptides. 



Another synthesis of phenylalanine from malonic ester, in which 

 Gabriel's phthalimide reaction is also made use of, is described by 

 Sorensen, namely, 



Br 



COOC 2 H 5 



I Bi 



CH 



C 



OOC 2 H 



COOC 2 H 5 

 CHBr + * 

 COOC 2 H 5 



X 



COOC 2 H 5 



I /< 



CH.NC 



Na 



CO' 



Bromomalonic ester 



Na 



/ C \ 

 \ 



CH.CH 2 C1 



COOC 2 H 5 

 ,CH . C 6 H 

 ^CO 



| X2 . 65 



COOC 2 H 5 



Sodium phthalimido- 

 malonic ester 



Phthalimidomalonic ester 



COONa 



| X CH 2 .C 6 H 5 

 NaOH C< 



> | \NH . CO . C 6 H 4 COONa 



COONa 



HC1 



COOC 2 H 5 



Benzylphthalimido- 

 malonic ester 



COOH 



/CHg.CfHg 



C( 



| \NH . COC 6 H 4 COOH 



'COOH 



Phthalimidobenzylmalonic 

 acid 



+ H 2 



CH 2 . C 6 H 5 

 = CH. 



COOH 



Phenylalanine 



NH 2 



Sodium phthalimidobenzyl- 

 malonate 



C 6 H 4 (COOH) 2 + C0 2 



Phthalic acid 



