Mutarotation

by James

in Carbohydrates

In our recent post on ring-chain tautomerism, we said that there are two isomers of D-glucose in its 6-membered ring (“pyranose”) form.

These two diastereomers – which, to make matters more confusing, are called “anomers” in the context of sugar chemistry –  differ in the orientation of the hydroxyl group on C-1. (Note that C-1 is a hemiacetal. )

  • In the “alpha” (α) anomer, the OH group on C-1 is on the opposite side of the ring as the chain on C-5.
  • In the “beta” (β) anomer, the OH group on C-1 is on the same side of the ring as the C-5 substituent.

Each of these two forms can be synthesized and isolated as pure compounds.

  • The alpha (α)  anomer of D-glucose has a specific rotation of +112 degrees in water.
  • The beta (β)  anomer of D-glucose has a specific rotation of +19 degrees. (18.7 actually, but rounding up to 19).

Here’s the interesting thing. When either anomer is dissolved in water, the value of the specific rotation changes over time, eventually reaching the same value of +52.5°. 

  • The specific rotation of α-D-glucopyranose decreases from +112° to +52.5°.
  • The specific rotation of β-D-glucopyranose increases from +19° to +52.5°.

This behaviour is called mutarotation (literally, “change in rotation”).

Hold on.  Isn’t specific rotation of a molecule supposed to remain the same?

Yes – if it is indeed the same molecule! 

And therein lies the answer to the puzzle. For when the solutions whose specific rotations have changed to +52.5° are analyzed, they are found to no longer consist of 100% alpha (α) or 100% beta (β) anomers, but instead a ratio of alpha (α) (36%) and beta (β) (64% ) isomers.

Wait. What happened here? How did the alpha convert to the beta, and vice-versa?

You may recall how we said in the last post on ring-chain tautomerism that the cyclic hemiacetal forms of sugars are in equilibrium with the straight-chain (“linear”) form.

That means that even if you start with a 100% pure sample of either the alpha or beta anomer, once it has been dissolved in water it can equilibrate, via the straight-chain form, to the other anomer. [If A is in equilibrium with B, and B is in equilibrium with C, then A is in equilibrium with C. That’s the Zeroth Law of Thermodynamics].

The 36:64 ratio of alpha (α) to beta (β) represents the distribution of isomers when D-glucose is in equilibrium in water at 25° C.

Is mutarotation unique to glucose?

No – it’s a general property of sugars, as well as (chiral) cyclic hemiacetals in general.

This phenomenon was first discovered in 1846 by French chemist Augustin-Pierre Dubrunfaut, who founded a factory for the production of alcohol from beet sugar. While studying the optical rotation of glucose, he noted that freshly dissolved glucose had a rotational value twice that which was previously observed in the literature. He also studied the mutarotation of lactose. (Interestingly, although Dubrunfaut was also the discoverer of fructose, he published no studies on its mutarotation – perhaps because fructose is one of the most rapidly mutarotating sugars) [Ref]

Interestingly, the structures of glucose and fructose had not been established at this point. It was not until 1895 that Tanret first reported on the two anomers of glucose, which readily explained Dubrunfaut’s observations.

Bonus question: given that the mechanism for the forward reaction was given in the previous post, can you draw a mechanism for the interconversion of alpha-D-glucose to beta-D-glucose? [A not uncommon exam question, by the way!]**

In the next post, we’ll discuss a tangent to ring-chain tautomerism: reducing sugars. 

Thanks for reading!

 


*If A is in equilibrium with B, and B is in equilibrium with C, then A is in equilibrium with C.

** Try and work out a mechanism for the conversion of a-glucopyranose to b-glucopyranose on your own. I’ll put a link to one solution in the comments.

 

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{ 3 comments… read them below or add one }

ajohnares

I think the alpha and beta explanation is a bit conflicting between the text and the scheme.

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James

Fixed! Thank you.

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James

Here’s one way to draw the mechanism of mutarotation. https://www.masterorganicchemistry.com/wp-content/uploads/2017/08/4-mechanism.png

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