II. CHEMISTRY 



547 



with optically active mandelic acid as an ester and fractionally crystallizing 

 to separate the two compounds. The best method of preparing (/-biotin 

 was by means of the ^arginine salt. 



A very different synthesis of biotin was achieved by Griissner et al.^^ 

 from 2-5-methoxybutyl-3-keto-4-carbethoxythiophane as shown in the re- 

 actions XXI-XXXIII. 



R = — CII3 or — C2H5 X = — CH2— CHs— CH2— CHjOCHs 



ROOC— CII— CII2 IIOOC— CH— CHa ROOC— CH— CH2 



\ 



s -^ 



/ 



O CH N=C— C Cli II2NOC— C CH 



X 



OH X 

 XXII 



OH X 

 XXIII 



XXI 

 ROOC— CH— CH2 ROOC— CH— CH2 ROOC— CH— CH2 



s 



s 



s 



HOOC— C CH ROOC— C CH ROOC— C' CH 



OH X 

 XXIV 



OH X 

 XXV 



CI X 

 XXVI 



ROOC— CH— CH, NH2NHOC— CH— CH2 N3 OC— CH— CH2 



\ 



s -^ 



/ 



ROOC— CH— CH NH2NHOC— CH— CH N3OC— CH— C 



I I I 



X XX 



XXVII XXV II I XXIX 



C2H5OOCNH— CH— CH, HBrNH2— CH— CH2 



\ 



s -> s 



/ 



C2H5OOCNH— CH— CH 



HBrNH2— CH— CH 



(CH2)3-CH2-OCH3 

 XXX 



(CH2)j-CH2Br 

 XXXI 



'' k. Griissner, J. P. Bourquin, and O. Schnider, Uelv. Chim. Acta 28, 517 (1945). 



