Synthesis of bromodeoxy sugars from hexoses, alditols, and aldonic acids

Abstract

Reaction of hexoses, anhydroalditols, and aldonic acids with hydrogen bromide in acetic acid leads to the formation of acetylated bromodeoxy compounds. The reaction proceeds by partial acetylation and formation of acetoxonium ions followed by substitution with bromide. Hexoses react only in the furanose form to give 6-bromo compounds. Most l,and 1,5-anhydrides of hexitols give monoor dibromides. Aldonic acids, or their lactones, yield monoor dibromolactones with bromine at C-2 and at the primary carbon atom. Some aspects of the chemistry of the bromolactones are discussed. INTRODUCTI ON Halogenated carbohydrates are valuable synthetic intermediates which may be used for the preparation of, for example, deoxy sugars, amino sugars, or unsaturated sugars. Numerous methods for the preparation of halogenated carbohydrates have therefore been developed and several reviews have been published (Refs. 1-3). I now describe a new method for the preparation of bromodeoxy compounds which consists simply of treating an aldose, anhydro-alditol, or aldonic acid with a saturated solution of hydrogen bromide in glacial acetic acid at room temperature. This reagent (henceforward called HBA) is a well known reagent in carbohydrate chemistry, used since the turn of the century for the preparation of glycosyl bromides (Ref. ). In this procedure an acylated (usually acetylated) sugar is treated with HBA at room temperature and the glycosyl bromide is usually formed in high yield as the only product. However, it has been found in a fe cases that reaction of carbohydrate derivatives with hydrogen bromide ffiay lead to substitution of an 0-acyl group with bromine at positions other than the glycosidic centre. Thus Fischer (Ref. 5) and, later, Freudenberg et al. (Ref. 6) found that penta-O-acetyl--glucopyranose gives tri-O-acetyl-6-bromo-6 -deoxy-a--glucopyranosyl bromide on treatment with anhydrous hydrogen bromide. PenEa-O-acetyl--galactopyranose behaves in a similar way (Ref. 7). Ohle et al. found that teatment of tri-O-acetyl-l,2-O-isopropylidene-a-D-glucofuranose with HBA gave bromodeoxy compounds which were not identifid (Ref. 8). Later work has shown that 6-bromo-6-deoxyand 2-bromo-2-deoxyfuranosyl bromides are formed in low yield in this reaction (Ref. 9). Recently Golding and coworkers showed that vicinal diols react rapidly at room temperature with HBA to give vicinal acetoxybromides (Ref. 10). Thus cis cyclohexane-l,2-diol (1) gave the trans bromoacetate () in almost quantitative yield. Based on earlier work by Boschan and Winstein (Ref. 11) they showed that the reaction takes place via the monoacetate (2) which forms an acetoxonium ion (3) that subsequently reacts with bromide ions to give . Cyclohexane-trans-l,2-diol did not give a bromocompound when treated with HBA. PAA( 50:11/12K 1386 C. PEDERSEN et al.