THE ACETOLYSES OF THEALPHAANDBETAMETHYLD-GLUCOPYRANOSIDE TETRAACETATES

Abstract

The acetolyses of the alpha and beta methyl D-glucopyranoside tetraacetates in 1 : 1 acetic acid -acetic anhydride 0.5 11d with respect to sulphuric acid were followed a t 25'C. by isotopic dilution analysis of products isolated after various intervals of tirne. The reaction of the a-glucoside was found to proceed mainly with inversion of the anomeric center. On the other hand, the 0-glucoside was found to undergo acetolysis with retention of configuration concurrent with anomerization. I t was shown t h a t the polarimetric changes observed in the course of the reactions could be satisfactorily accounted for on the basis of these reaction routes. Reaction mechanisms are suggested. Montgomery et al. (15) investigated the use of either sulphuric acid or zinc chloride in acetic acid -acetic anhydride as a reagent for the acetolysis of glycosides. I t was shown that in many cases the glycoside was converted to a mixture of the anomeric sugar acetates in high yield and the procedure has been widely used for the cleavage of acetal bonds in carbohydrate chemistry. Studies on the acetolysis of the anomeric methyl D-arabinopyranoside triacetates showecl these reactions to be highly complex (15). A solution a t 20°C.of nlethyl a-D-arabinopyranoside triacetate in a mixture of 4y0 sulphuric acid in 7 : 3 acetic anhydride -acetic acid changed sharply in specific rotation from -lgO to -114O in one minute and declined to an equilibrium value of -ZO a t the end of 20 min. The hexaacetate of aldel~ydo-D-arabinose and p-D-arabinopyranose tetraacetate were isolated in yields of soy0 and 12%, 1-espectively, from the product. However, when the experiment was interrupted a t the rotation peak of -114", a 14% yield of methyl /3-D-arabinopyi-anoside triacetate was obtained. Thus, it was apparent that the rapid initial rise in rotation was d~~e to the anomerization of the a-anoiner to the more stable /3-form. This possibility was strengthenecl by the observ a t' loll that ~nethyl @-D-arabinopyranosicle triacetate under the same conditions gave a solution which changed in specific rotation from -184' t o a constant equilibrium value of -17" in three minutes. The hcxaacetate and the p-tetraacetate could be isolated in 56y0 and 11% yields, respectively, after 24 hr. The occurrence of the hexaacetate in the reaction products suggested that the C1 to ring-oxygen bond may cleave in preference to the C1 to methoxyl group bond. This idea was substantiated by the acetolysis of the p-arabinoside under the milder conditions of O.l6Y0 sulphuric acid in 7 : 3 acetic anhydride -acetic acid mixture. Both the anomeric forms of methyl hemiacetal pentaacetates (I) were isolated in good and approximately equal yields. I t is to be notecl that liLl~nz~script received September 7 , 1954 More recently, Lindberg (1, 2, 13) has obtained further evidence that the acetolysis of an unstable 0-acetylated allcyl glycopyranoside is accompanied by anomerization. This was shown to be so for a variety of glucosides (13), galactosides ( I ) , and a xyloside (2...

THE EFFECT OF CHLORINE SUBSTITUTIONS AT THE C2-ACETOXY GROUP ON SOME PROPERTIES OF THE GLUCOSE PENTAACETATES

“…I t seems clcar (10, 11) that acetylated alkyl glycopyranosides undergo anonjerizatioll under conditions for acetolysis by way of an intra~~lolecular mechanism. 1,ernieux et al (10) P-D-glucopyranoside tetraacetate under the conditions used herein for the anomerization of the glucopyranose pentaacetates. Since it must be expected that the anomerization of 0-D-glucopyranose pentaacetate woulcl have a tendency to follow the sanle path as the anomerization of methyl P-D-glucopyranoside tetraacetate, any consideration of the mechanism of the latter reaction must first deal with the possibility that the reaction proceeds by way of an intramolecular mechanism.…”

Reaction Kinetics and Mechanism of Sulfuric Acid‐Catalyzed Acetolysis of Acylated Methyl L‐Ribofuranosides

“…[9] Very few investigations exist on the acetolysis of furanoses [10] and even fewer targeting the mechanistical issues. [11] In the current work, we report our results on the mechanism of the acetolysis and concurrent anomerization of 1,2,3,5-tetra-O-acetyl-and 1-O-acetyl-2,3,5-tri-O-benzoyl--ribofuranoses as followed by in situ 1 H NMR spectroscopy. The reactions were carried out in a mixture of acetic acid and acetic anhydride with a catalytic amount of sulfuric acid.…”

“…This observation can be explained by the formation of a cis-fused dioxonium ion intermediate (J) via neighboring group participation by the acetoxy group at C(2) after dissociation of the glycosidic bond. [1,23] This results in the intermediate being 1,2-trans directing, considering the nucleophilic attack by acetic acid leading to the fast formation of the β-anomer 4. It is also very likely that the trans-1,2-configuration in the acetylated methyl β-ribofuranoside 2 activates the cleavage of the glycosidic bond through neighboring group participation, but as the anomerization of compounds 1 and 2 is evidently faster than the formation of 3 and 4, this phenomenon is undetectable.…”

“…During this period, several mechanistic proposals related to the acid-catalyzed acetolysis and the accompanying anomerization of different alkyl glycopyranosides, still accepted today, were established. The early work concerned both the site of anomeric activation, [1,2] as well as the acid species involved in the acetic acid/acetic anhydride mixtures used. [3,4] Miljković has recently investigated the electronic effects influencing the acetolysis of pyranosides.…”

THE RELATIVE REACTIVITIES OF 1,2-trans-SUGAR ACETATES

“…The unstable anomers of most of the acetylated glycosyl halides are not suitable for study because of their extremely high reactivity (1.4, 22). On the other hand, the much more inert acetylated alkyl glycosides possess the undesirable property of undergoing reaction by way of very con~plex reaction routes (19). Both the anomeric forms of sugar acetates are usually sufficiently unreactive to allow purification arid the results of studies on pentaacetates of glucose (15), galactose (14), and mailnose (16) suggest that these substances undergo reaction a t the anomeric center in a reasonably straightforward fashion.…”