130 THE CHEMICAL CONSTITUTION OF THE PROTEINS 



Proline. 



Just a year before E. Fischer obtained this compound by the hydro- 

 lysis of caseinogen, it was synthesised by Willstatter in 1900 from 

 sodium malonic ester and trimethylene bromide by the following re- 

 actions : 



COOC 2 H 6 COOC 2 H S COOC 2 H, 



BrCH 2 .CH 2 .CH 2 Br | Br 2 I 



CHNa -- > CH.CH 2 .CH 2 .CH 2 Br -- > C(Br).CH 2 . CH 2 . CH 2 Br 



COOCaH, COOC 2 H 5 COOC 2 H 5 



Bromopropylmalonic , S-Dibromopropylmalonic 



ester ester 



CH 2 CH 2 CH 2 CH 2 



NH S /CONH 2 H 2 



-- > CH 2 C/ -- > CH 2 CH . COOH 



\ / \CONH., \ / 



NH NH 



It was also synthesised by E. Fischer in 1901 from ry-phthalimido- 

 propylmalonic ester which he employed in the preparation of ornithine. 

 The bromine derivative of this compound when treated with ammonia 

 gave a complex mixture of products, which, after hydrolysis by hydro- 

 chloric acid at 100 G, gave phthalimide and 0-pyrrolidine carboxylic 

 acid : 



/CO, /COOC 2 H 6 NH CQ CH 2 -CH 2 v 



C 6 H/ \N.CH 2 .CH 2 .CH 2 .CBr -- >C 6 H/ \NH+ I 



Nx C CH 2 -CH . COOH 



Sorensen and Andersen in 1908 synthesised proline by the sodium 

 phthalimidomalonic ester method, a yield of about 80 per cent, being 

 obtained. Sodium phthalimidomalonic ester is condensed with tri- 

 methylene bromide, 



COOC 2 H 5 COOCoH 6 



I /Na + Br . CH 2 . CH 8 . CH 2 Br = NaBr + | y CH 2 . CH 2 . CH 2 Br 



c C G O 



COOC 2 H 5 COOC 2 H 5 



the resulting 7-bromopropyl-phthalimidomalonic ester is heated in alco- 

 holic solution with sodium hydroxide and the product so formed is 

 evaporated with hydrochloric acid. Proline is obtained instead of the 

 expected a-amino-S-ethoxyvalerianic acid, ring formation occurring just 

 as in the other methods of preparing proline : 



COO . Na 



| ,CH 2 . CH 2 . CH 2 OH CH 2 CH 2 



C\ -> | | + C e H 4 (COOH) 2 + CO 2 + K 2 O 



i \NH.CO.C 6 H 4 .COOH CH Q CH . COOH 



COONa NH 



