12 CHEMICAL STATICS 



In other words, the chloracetyl group, introduced to protect 

 the NH 2 group of the amino-acid is, after it has performed its 

 protective function, itself transformed into an amino-acid group, 

 through the replacement of the halogen atom by NH 2 . Obvi- 

 ously, other halogen-containing acid groups may be used in place 

 of chloracetyl, and in this way a great variety of amino-acid groups 

 can be introduced into the NH 2 group. Thus Fischer employs: 



Chloracetyl-chloride for the introduction of glycyl. 

 a-Bromopropionyl-chloride for the introduction of alanyl. 

 1-a-Bromopropionyl-chloride for the introduction of d-alanyl. 

 ex-Bromobutyryl-chloride for the introduction of a-aminobutyryl. 

 a-Bromisocapronyl-chloride for the introduction of leucyl. 

 a-Bromophenylacetyl-chloride for the introduction of phenylglycyl. 

 a-Bromohydrocinnamyl-chloride for the introduction of phenylalanyl. 

 a-Phenylbromopropionyl-chloride for the introduction of phenylalanyl. 

 a-5-Dibromovaleryl-chloride for the introduction of prolyl. 



Fumaryl-chloride for the introduction of asparagyl. 



By this method the chain of amino-acids is lengthened at the 

 amino-group end. Theoretically, it appeared possible tcValso. 

 lengthen the chain at the carboxyl end of the molecule, by acting 

 upon the esters of the amino-acids with the acid chlorides of 

 other amino-acids. Until 1904, however, the acid chlorides of 

 amino-acids were unknown and all attempts to prepare them had 

 failed, owing to the same reason which limits the use of the first 

 method of synthesizing poly-amino-acids, described above, namely 

 the reactivity of the NH 2 group. It will be recollected that 

 Fischer found that the NH 2 group could be protected by the 

 introduction of radicals, and, utilizing this fact, in 1904 Fischer 

 succeeded in devising a method of preparing the acid chlorides 

 of the amino-acids (17). The acid chlorides thus prepared react 

 with the esters of other amino- or poly-amino-acids to form poly- 

 ami no-acid chains of greater length. Thus: 



C 4 H 9 .CHBr.CO.NH.CH 2 COCl + 2 NH 2 .CH 2 .COOC 2 H 5 



(Bromisocapronylglycyl chloride) (Glycin ester) 



= HC1NH 2 .CH 2 .COOC 2 H 5 + C 4 H 9 .CHBr.CO.NH.CH 2 CO.- 



NH.CH 2 COOC 2 H 5 . 



(Glycin ester hydrochloride) (Bromisocapronylglycyl-glycin ester) 



Subsequent saponification of the bromisocapronyl-glycyl-glycin 

 ester and treatment with ammonia yields the poly-amino-acid (tri- 

 peptid) leucyl-glycyl-glycin: 



C 4 H 9 .CH(NH 2 ).CO.NH.CH 2 .CO.NH.CH 2 .COOH. 



