II. t'llKMISTUY 191 



synthesis of i.-ascoihic acid, its coin'orsioii into \hv corresponding osone is 

 Ix'st acci)mj)lislu>d liy means of lien/aldehyde in iiot a(ineous alcohol,''^"'''* 

 whereas witli the luwosazones, which are intermechates in the synthesis of 

 the next hi<j;her nienil)eis in the ascorbic acid series, it has been found 

 adx'antaseous to use fuming hydrochloric acid'-' " because, unlike the 

 pentosazones and the metiiyl i)ent()sazones, they are only sparinj^ly soluble 

 in a(iueous alcohol and conseciuently they react very slowly with benzalde- 

 hyde. The oxidation of aldoses with cupric acetate in hot a(iueous alcohol 

 fiist effectively utilized by Weidenhasen"" has been reiiu'estigatcd,"**' "= 

 and it appears to be an excellent method for the preparation of osones. 

 Although the osone-cyanohydrin reaction has been extensively used for the 

 synthesis of L-ascorbic acid and its analogs'^' '•'• ''-"*^' ^'^^ on a small scale, 

 it is not an economical method in spite of simpler alternative procedures 

 for preparing osones,^^"' b. c, 62 j^,^j hence it is unsuitable for the large-scale 

 manufacture of ^'itamin C. 



Method 2. Simultaneous Lactonization and Isomerization of 

 AN Appropriate 2-Keto Acid or Ester 



This method is at present the best method for synthesizing vitamin C 

 on a large scale, provided that the requisite keto acid or ester is available; 

 it is also the most efficient for preparing analogs of ascorbic acid. 



In the synthesis of L-ascorbic acid, methyl 2-keto-L-gulonate (XXXI), 

 obtainable from the acid (XXXIII) by acid-catalyzed esterification,^'* by 

 diazomethane,^'* and also by auto-esterification,"^ is boiled for a few minutes 

 with a methanolic solution of sodium methoxide.^^' ^® The sodium ascorbate 

 (XXXII) thus formed is then converted to the free ascorbic acid (I) by 



56 E. P^ischer and K. F. Armstrong, Ber. 35, 3141 (1902). 



" E. Fischer, Ber. 22, 87 (1889). 



"» R. Weideiihageii, Z. Wirtschajtsuruppc Zuckerind 87, 711 (1937). 



"'' L. L. Salomon, J. J. Burns, and C. G. King, J. Am. Chem. Soc. 74, 5161 (1952). 



"<= J. K. Hamilton and F. Smith, J. Am. Chem. Soc. 74, 5162 (1952). 



'^ W. X. Ilaworth, E. L. Hirst, and J. K. X. Jones, J. Chem. Soc. 1937, 549. 



" Marguerite Steiger, Helv. Chim. Acta 18, 1252 (1935). 



*" T. Reichstein, L. Schwarz, and A. Griissner, Helv. Chim. Ada 18, 353 (1935). 



«' T. Reichstein and V. Demote, Festschr. Emil Barcll 107 (1936). 



« I. Stone, U. S. Pat. 2,206,374 (1940). 



" T. Reichstein and A. Griissner, Helv. Chim. Ada 17, 311 (19.34). 



" W. X. Haworth, E. L. Hirst, J. K. N. Jones, and F. Smith, Britisli Pat. 443,901 



(19361. 

 "5 K. Maurer and B. Schiedt, Ber. 66, 1054 (1933); 67, 1239 (1934). 

 «" H. Ohle, H. Erlhach, and H. Carls, Ber. 67, 324 (1934). 



