II. CHEMISTRY 197 



2-keto-L-guloiii(' acid at 120° is treated with a haloj>;en acid. Witliiii a few 

 minutes the conversion is complete and a 70 to 80% yield of L-ascorhic 

 acid can be isolated.'" Finally, it may be noted that 2-keto esters such as 

 XXXI and LVI can be converted into the corresponding ascorbic acid by 

 heating in aqueous solution with magnesium, iron, nickel, cobalt, cadmium, 

 and zinc.^^' ^^ As might have been anticipated, other workers have used 

 esters other than the methyl, namely, the butyl and ethyl esters. '**• ^^ 



Method 3. Benzoin Condensation of Sugars ^vith Ethyl 

 Glyoxylate or Ethyl Mesoxalate 



This excellent method of general application may be used not only for 

 the synthesis of ascorbic acid but for its many analogs. Thus, L-threose 

 (LIX) or tetraacetyl-L-threose cyanohydrin (LVIII), which affords L-thre- 

 ose upon treatment with alkali, will condense wdth ethyl glyoxylate (LX) 

 in an alkaline medium to give L-ascorbic acid (I).^^ Ethyl mesoxalate^* can 



CO— 1 

 CN \ HO-C 



CHOAc CHO \ v„nxt„ HO-C 



H— C— OAc or H— C— OH X H— CO- 



AcO— C— H HO— C— H HO-C— H 



CHjOAc CHjOH CHjOH 



LVIII LIX I 



replace ethyl glyoxylate in this reaction. The method is limited in some 

 instances by the inaccessibility of some of the starting materials, as is the 

 case with L-threose. Recently it has been claimed that ethyl hydroxy 

 ethoxyacetate is superior to ethyl glyoxylate for use in the above condensa- 

 tion, 90 % yields of \'itamin C being reported. ^^ 



Method 4. Claisen Condensation of Esters of Hydroxy Acids 



The simplest true analog of ascorbic acid, oxytetronic acid (LXII), is 

 derived from the action of potassium upon ethyl benzoyl oxyacetate'"" 



" R. Pasternak and P. P. Regna, U. S. Pats. 2,165,151; 2,165,184 (1939). 

 'Japanese Pat. 161,770 (1944). 



"A. II. Ruys and J. F. Lemmens, U. S. Pat. 2,491,933 (1950). 

 *« British Pat. 601,789 (1948). 



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

 »»B. Helferich, German Pat. 683,954 (1939); U. S. Pat. 2,207,680 (1940). 

 »» P. L. Stedehouder, Dutch Pat. 59,711 (1947). 

 '«« F. Micheel and F. Jung, fier. 66, 1291 (1933). 



