A Study of Steric Effects on Nitromethylene Acidity and the Mechanism of Epimerization in Partially Blocked Nitro Hexoses

Abstract

The extent of nitronate formation in seven methyl 4,6-O-benzylidene-3-deoxy-3-nitrohexopyranosides and four methyl 4,6-O-benzylidene-2,3-dideoxy-3-nitrohexopyranosides in dilute potassium hydroxide solution was compared by means of u.v. spectroscopy. Considerable differences were found to exist in the nitromethylene acidities, and these were correlated with stereochemical features of the molecules. A facile manno → gluco epimerization occurring in this series was investigated. It was shown that, in alkaline alcoholic solution, the epimerization proceeds by an elimination–addition via an intermediate nitroalkene if the hydroxyl group at C-2 is acetylated. However, if the hydroxyl is free, the nitroalkene is not an intermediate and, in accord with the low nitromethylene acidity in this particular case, the mechanism is suggested to involve a reverse Henry reaction.

The Synthesis of gem-Halonitro Sugars and Their Conversion into Epoxynitro Sugars

“…In the account that follows, the chemistry of compounds having a cis-fused 4,6-benzylidene acetal ring will be treated first, and that of trans-fused acetals will be dealt with thereafter. A recent study (9) had revealed considerable differences in the ease of nitronate formation (i.e., proton abstraction from C-3) in dependence of the over-all configuration of the molecule. Since the process of nitronate formation has to precede introduction of a halogen atom it could be expected that there would also be a strong influence of configuration upon the course of halogenation.…”

Some Synthetic Interconversions in the Nitrocyclohexane System

“…Separation was achieved on a silica gel column (100 g) using the same solvent. The fastermoving product (14) was obtained as a solid that was recrystallized from carbon tetrachloride -petroleum ether; m.p. 92-93".…”

“…8 it reacts, even without boron trifluoride catalysis, to give nitronic esters that may subsequently undergo various kinds of irreversible transformations (13a). F o r nitro sugars, pK, values of 8-11 have been reported (11,14), suggesting that some of them might be borderline cases in this respect. The selective methylation of hydroxyl groups in 1 placed confidence in possible applications o f diazomethane t o nitro sugars for which the customary base-promoted alkylation methods, although never actually tried, prima facie do not recommend themselves, both because they would Can.…”

“…Downloaded from www.nrcresearchpress.com by 18.236.120. 13 likely effect 0-and (or) C-alkylation involving the nitro function (13a), and because of the proclivity of many nitro sugar derivatives to incur configurational and structural changes in basic media (11,136,(14)(15)(16)(17). In the meantime, the diazomethane method has, in fact, been utilized in the synthesis o f methyl 3,6-dideoxy-2,4-di-0-methyl-3-nitro-a-D-glucopyranoside (1 8).…”

Configurational Equilibria in Methyl 3,6-Dideoxy-3-nitro-α-L-hexopyranosides

“…It has been realized in those studies that the effect (41, the nonbonded interaction between a group attached by a double bond to the ring (here, =NO,-) and a vicinal, equatorial substituent (here, -OH), has a profound influence upon conformational preferences and configurationai interconversions (2,3). On the basis of free energy calculations (2) one may predict the behavior of other groups of nitro glycosides in alkaline solution, and it is the purpose 'Part XXV in a series on reactions of nitro sugars.…”