A Procedure for the Preparation of 2-Desoxy-D-glucose.--FRANCiS B. CRAMER. Moderate quantities of 2-desoxy-D-glucose have been repeatedly prepared for use in experimental work being carried out at this laboratory. The procedure evolved is a modification of the original glucal method of Bergmann (1). Although the method has by no means been brought to a state of perfection, it is effective and reliable.
The chief advantage of the procedure is that it avoids unnecessary isolation of intermediates, which is wasteful and time-consuming. Glucose is acetylated rapidly at high temperature with a trace of sulfuric acid catalyst. Acetobromo glucose is prepared immediately by the addition of hydrogen bromide to the acetylation mixture. The resulting solution is added directly to a reducing mixture containing sodium acetate to neutralize excess hydrogen bromide (2). At this point the reaction product, glucal triacetate, is isolated and purified. The glucal triacetate is rapidly de-esterified by boiling methanol using a sodium methylate catalyst (3), the solvent is removed, and the resulting glucal is hydrated by standing overnight with very dilute sulfuric acid at room temperature.
The successful use of 0.035 normal sulfuric acid for the conversion of glucal to desoxyglucose is scarcely compatible with the generally accepted theory that sulfuric acid adds to the double bond of glucal and is subsequently removed by hydrolysis (4). A more probable mechanism would be the proton-catalyzed opening of the oxygen bridge of the glucal, resulting in a vinyl alcohol structure which would instantly rearrange to the aldehyde form.
Difficulty is sometimes experienced in obtaining the first seed crystals of glucal triacetate and desoxyglucose. Glucal triacetate should be purified by several vacuum distillations, retaining the middle fraction. Scratching and chilling in a dry-ice bath should induce crystallization. Desoxyglucose seed crystals are best obtained through purification by the method of Bergmann (1), followed by repeated trituration of the syrup with absolute ether and drying in a vacuum over solid sodium hydroxide.
The procedure as presented is not entirely adaptable to the preparation of the 2-desoxypentoses. The acetobromo pentoses may be prepared as described but extremely low yields of the glycal diacetates are obtained by direct addition of the solution to the reducing mixture. The glycal diacetates must not be boiled with sodium methylate, but may be de-esterified by the method of Isbell (5). Hydration of the glycals should be carried out at a low temperature.