194 



ASCORBIC ACID 



The keto acids and their esters required for this particular method of 

 synthesis have been made in a variety of ways which fall into four main 

 groups. 



1. Oxidation of osones. 



2. Oxidation of aldonic lactones. 



3. The conversion of an acid chloride to a keto nitrile followed by hy- 

 drolysis. 



4. Oxidation of ketoses or certain of their carbonyl derivatives. 



1. Oxidation of osones. When available, an osone such as L-gulosone 

 (XLIV) can be oxidized with bromine to the corresponding 2-ketogulonic 

 acid (XXXIII) in the manner previously established for the preparation 

 of 2-keto-D-gluconic acid.^^ 



^. Oxidation of aldonic acids.An example of this apparently general reac- 

 COOH COOH 



. I I 



tion CHOH -^ CO is found in the oxidation of L-gulonic acid to 2-keto- 



L-gulonic acid with chromic acid^^ or with chromates in the presence of a 

 vanadium catalyst.''^ This reaction, claimed to give good yields, has also 

 been applied to d-" and to L-galactonic acid.^^ 



3. The conversion of an acid chloride to a keto nitrile followed by hydrolysis. 

 This method, which makes use of a classical reaction in organic chemistry, 

 is also a general reaction and appears to be applicable to the preparation 

 of L-ascorbic acid and its analogs. The sugar acid (XLV) is converted to the 

 acid chloride (XL VI) which is then treated with silver cyanide to give the 

 keto nitrile (XLVII). Hydrolysis of the latter with hydrochloric acid then 

 provides the desired keto acid (XLVIII).^^ 



'^ C. Neuberg and T. Kitasato, Biochem. Z. 183, 485 (1927). 



'* 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 (19-40). 



" P. P. Regna and B. P. Caldwell, J. Am. Chem. Sac. 66, 243 (1944). 



'8 H. S. Isbell, J. Research Natl. Bur. Standards 33, 45 (1944). 



" R. T. Major and E. W. Cook, U. S. Pat. 2,368,557 (1945). 



