Preparation of ascorbic acid intermediates

#L-ascorbic acid, or vitamin C, is required in the human diet and is widely sold in tablet form and as an additive in various foodstuffs to meet this need. In all animals except primates and guinea pigs L-ascorbic acid is biosynthesized from D-glucose. The final step in this biosynthesis is the enzymatic conversion of L-gulono-1,4-lactone to L-ascorbic acid. British Pat. No. 763,055 discloses the conversion of L-gulono-1,4-lactone to L-ascorbic acid in about 40% yield by the use of an enzymatic oxidation system.

#L-ascorbic acid and some of its derivatives are employed as antioxidants in foodstuffs to prevent rancidity, to prevent browning of cut fruit and in meat curing. D-ascorbic acid may also be used.

#Attempts to effect the direct conversion of gulono-1,4-lactone to ascorbic acid by chemical means have only partly been successful since over-oxidation and degradation reactions product undesirable by-products. However, low yields of L-ascorbic acid have been produced by oxidation. For example, Berends and Konings, Rec. Trav. Chim. des Pays-Bas, 74, 1365 (1955), disclose the use of Fenton's reagent to give a 10% yield of L-ascorbic acid. The most successful and common method of producing L-ascorbic acid is based on a multi-step synthesis from D-glucose going through sorbose and 2-ketogulonic acid as described by Reichstein and Grussner, Helv. Chim. Acta., 17, 311 (1934).

#To 11.2 ml (113 mmol) of benzaldehyde and 2.3 ml (57 mmol) of methanol was added 5.04 g (28.3 mmol) of L-gulono-1,4-lactone followed by 1.12 ml (13.4 mmol) of concentrated hydrochloric acid. On stirring for 20 hrs at room temperature the initially mobile slurry turned solid. The reaction mixture was triturated with ether and filtered. The solids were washed with ether, two times with water, and then ether. After drying in vacuo, the white solid weighed 6.2 g (16.1 mmol, 57%; based on unrecovered gulonolactone, 82%), mp 177.degree.-180.degree.. Recrystallization from benzene--acetone afforded analytically pure material, mp 180.degree.-183.degree.: [.alpha]sub.D.sup.23 +64.5.degree. (DMF); ir (KBr) 3340, 1733 cm.sup.-1 ; nmr (DMSO-d.sub.6) .delta..sub.H 3.65 (s, 3, --OCH.sub.3), 3.86-4.53 (m, 6), 5.66 (s, 2, --OCHO--), 6.10 (d, 1, J=5, --OH), 7.2-7.63 (m, 10, aromatic); ms 386 (1.9), 385 (5.2), 297 (13.1), 149 (25.9), 107 (40.6), 106 (21.7), 105 (100), 91 (57.8), 79 (26.5), 78 (10.7), 77 (38.9).

#Anal. Calcd for C.sub.21 H.sub.22 O.sub.7 : C, 65.27; H, 5.74. Found: C, 65.22, H, 5.74.

#The method of Example I may be repeated replacing benzaldehyde with each of the following aldehydes: