III. INDUSTRIAL PREPARATION 209 



III. Industrial Preparation 



FRED SMITH 



The "enediol" ring system present in ascorl)ic acid may l)e produced by 

 a number of methods (see p. 188) and the patent literature shows that most 

 of them have been investigated with the object of making L-aseorbic acid 

 on a large scale. 



The osone method requires L-lyxosone (L-xylosone) which may be made 

 from either L-lyxose^ or L-xylose.- However, in spite of the fact that osones 

 can be prepared in good yield directly from the sugars with cupric acetate 

 by two methods, one made possible by the use of methyl alcohol as a 

 solvent^'^ and the other by controlling the pH,^ the method is uneconomical 

 for the industrial preparation of L-ascorbic acid. The reason for this is that 

 neither of the two required pentose sugars is readily accessible at the present 

 time. 



Another method that has been examined for synthesizing L-ascorbic acid 

 involves the condensation of glyoxylic ester with L-threose in the presence 

 of a base; instead of L-threose one can use its cyanohydrin which is pre- 

 pared from L-xylose or L-lyxose.'^ As has been stated already, these two 

 pentose sugars are inaccessible and so is L-threose, and hence this method 

 of synthesizing L-ascorbic acid is likewise of no commercial value at present. 



The most useful method at the present time is based upon the observation 

 that an a-keto-iS , 7-dihydroxy carboxylic acid (I) may be transformed into 

 a compound having the ascorbic acid ring system (III) either directly by 

 the agency of an acid or indirectly by first converting the acid into an 

 ester (II) and then treating the latter with sodium methoxide.^ 



Researches on the large-scale preparation of L-ascorbic acid have, there- 

 fore, been directed mainly toward the development of methods for produc- 

 ing the reciuisite a-ketohydroxy acids, namely, 2-keto-L-gulonic and 2-keto- 

 L-idonic acid. Although it is claimed that L-idonic acid may be oxidized 

 to the corresponding 2-keto acid by a fermentation process^ and that 

 L-gulonic acid can be oxidized to a 2-keto acid by means of chromic acid,'"' " 



* R. G. Ault, D. K. Baird, H. C. Carrington, W. N. Haworth, R. W. Herbert, E. I- 

 Hirst, E. G. V. Percival, F. Smith, and M. Stacey, J. Chem. Sac. 1933, 1419. 



- T. Reichstein, A. Griissner, and R. Oppenauer, Helv. Chim. Acta 16, 1019 (1933). 

 3 L. L. Salomon, J. J. Burns, and C. G. King, J. Am. Cheyn. Soc. 74, 5161 (1952). 



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



* R. Weidenhagen, Z. Wirtschaflgruppe Zuckerind. 87, 711 (1937). 

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



' B. Helferich and O. Peters, Her. 70, 465 (1937); German Pat. 637,448 (1936). 



8 T. Reichstein and A. Grussner, Helv. Chim. Acta 17, 311 (1934). 



9 U. S. Pats. 2,421,611 and 2,421,612 (1947). 



>" R. Pasternak and P. P. Regna, U. S. Pat. 2,153,311 (1939). 

 " R. Pasternak and P. P. Regna, U. S. Pat. 2,188,777 (1940). 



