Epimerization

1. What are D-glucose and D-mannose?

  • Both are aldoses (sugars with an aldehyde group).

  • They are epimers at carbon 2 (C2).

    • In D-glucose, the OH at C2 is on the right in the Fischer projection.

    • In D-mannose, the OH at C2 is on the left.

  • They differ only at one chiral center (C2) → that makes them epimers.

2. What happens under basic conditions?

Under strong base (e.g. NaOH), the sugar undergoes a reversible reaction called tautomerization:

a) Formation of enediol intermediate:

  • The base removes a proton (H⁺) from the α-carbon (C2) next to the carbonyl group (C1).

  • This creates a double bond between C1 and C2, and both C1 and C2 now bear OH groups → this is the enediol form.

b) Re-tautomerization (reforming the carbonyl):

  • The enediol can then re-form the original aldehyde at C1 by shifting electrons back.

  • BUT: the OH at C2 can now go either to the left or the right, because planarity is introduced at the enediol stage and the stereochemistry is lost.

  • This results in a mixture of D-glucose and D-mannose.

⚠ Why does this matter?

  • This reaction scrambles the stereochemistry at C2.

  • It turns pure D-glucose (or pure D-mannose) into a mixture of both due to the reversible enediol intermediate.

🔁 Summary:

Under strong basic conditions, D-glucose undergoes tautomerization to form an enediol intermediate. When the carbonyl group reforms, the configuration at C2 can change, resulting in a mixture of D-glucose and D-mannose, which are epimers. Since the base disrupts stereochemistry, chemists avoid using strong base when working with sugars.