[Nescafe]

Hi,


I read that Anomeric effect "describes the tendency of heteroatomic substituents adjacent to a heteroatom within a cyclohexane ring to prefer the axial orientation instead of the less hindered equatorial orientation that would be expected from steric considerations".

I concluded based on that in glucose the hydroxyl neighboring the Oxygen in the ring should be in the axial position ( at least more so) than the equatorial. Then I read that "regardless of the configuration of the starting D-glucose, a solution will gradually move towards being a mixture of approximately 64% β-D-glucopyranoside and 36% of α-D-glucopyranose".

The α-glucose is the one which has the OH in the axial position, the β, in the equatorial. So how is it that the β- glucopyrnaoside is more favored, where as based on the anomeric effect the α-glucose is the more stable substrate?

:S

Nescafe.

[Babcock_Hall]

My recollection is that when one makes methyl-glucoside from methanol and glucose, the alpha is favored over the beta isomer under equilibrium conditions:  http://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/carbhyd2.htm

There was an article about the anomeric effect in the 1984 in Accounts of Chemical Research by A.J. Kirby.  I think that Michael Sinnott has also worked in this area:  http://pubs.acs.org/doi/abs/10.1021/ja00283a025

[orgopete]

Okay, I am going to step in. Since I don't have the data before me, I could be very wrong. First, there are two different mechanisms that can be involved and two different kinetic or thermodynamic situations present.

If the formation of a pyranoside occurs from addition of an OH to a CHO group, both can form and reverse. This reaction may well favor the beta-pyranoside as it is equatorial. If the reaction occurs with an acid catalysis, then loss of water can occur with neighboring group participation of the non-bonded electrons of the oxygen. If the pyranoside has a pseudo-chair conformation, then it should open an a trans-diaxial manner. This will result in the non-bonded electrons and the OH being axial, or alpha. However, this describes a kinetic result. While it may be favored, I expect that someone can find conditions in which the opposite stereochemistry results.

[Dan]

The "anomeric effect" is the name of the observation that exo electronegative groups at the anomeric centre of a pyranose tend to be more stable in the more sterically hindered axial position. It relates to acetal/hemiacetal formation under thermodynamic control. There are are a several factors that can be invoked to explain the anomeric effect, including arguments based on dipole alignment and solvent polarity, and most importantly a stereoelectronic effect of favourable n:rarrow:σ* overlap.

The situation you have is the α-anomer is stabilised by the factors contributing to the anomeric effect, but on the other hand the β-anomer is less sterically hindered. There are two opposing effects: the anomeric effect and sterics. It is not always simple to decide which one will dominate for a given molecule - it is fairly easy to explain the product distribution, but predicting it can be extremely difficult.