The Reaction of Dimeric Tri-<i>O</i>-acetyl-2-deoxy-2-nitroso-α-<scp>D</scp>-hexopyranosyl Chlorides with Alcohols

Abstract

The kinetics of the reactions of dimeric tri-O-acetyl-2-deoxy-2-nitroso-α-D-glucopyranosyl chloride (1) with simple aliphatic alcohols (4 mol equiv) in dimethylformamide to form alkyl tri-O-acetyl-2-oximino-α-D-arabino-hexopyranosides (5) were investigated by n.m.r. and optical rotation. It is concluded that the conversion of 1 to 5 proceeds basically by way of three successively formed intermediates, namely, the monomeric form (2) of 1, the tri-O-acetyl-2-oximino-α-D-arabino-hexopyranosyl chloride (3), and the tri-O-acetyl-1,5-anhydro-2-deoxy-2-nitroso-D-arabino-hex-1-enitol (4). Direct evidence was obtained only for the intermediacy of 3 and the transient existence at low concentration of an uncharacterized intermediate which may be the β-anomer of 5. The intermediate 4 could form directly from 2 and thereby provide a mechanism for the formation of 5 which by-passes 3. However, the kinetic investigations showed this route to be of very minor, if any, importance. In all cases, the rate of the disappearance of 1 was virtually the same and within experimental error the same as for the isomerization of 1 to 3 in the absence of the alcohol for which the rate-controlling stage is dissociation of 1 to 2. Methanol reacts with 4 only about 5 times faster than does t-butanol.The utility of the reaction for the preparation of oximinoglycosidic structures related to disaccharides is illustrated by glycosidations of 1,2;3,4-di-O-isopropylidene-α-D-galactopyranose, 1,2;5,6-di-O-isopropylidene-α-D-glucofuranose both by 1 and by the dimeric tri-O-acetyl-2-deoxy-2-nitroso-α-D-galactopyranosyl chloride (6) and of 2,3;5,6-di-O-isopropylidene-α-D-mannofuranose by 1. The reaction of 6 with 1,2,3,4-di-O-isopropylidene-α-D-galactopyranose provided an 8.7% yield of the β-oximinoglycoside along with an 80% yield of the α-anomer.