Heyns rearrangement

What is Heyns rearrangement?

The Heyns rearrangement, a rapid rearrangement of α-hydroxy imines (including α-hydroxy Schiff bases) into stable α-aminocarbonyl compounds, was first reported by Heyns in 1952. The reaction occurs under nonreducing conditions and is commonly referred to as the Heyns rearrangement. The corresponding α-ketoamines are known as the Heyns rearrangement products or Heyns products.

Heyns rearrangement - general reaction scheme - Heyns rearrangement products - Heyns products
Heyns rearrangement

It is important to note that the formation of imines or Schiff base derivatives is thermodynamically reversible, while the α-hydroxyl group facilitates the Heyns rearrangement, leading to the formation of stable α-ketoamines. The formation of Schiff base is the rate-limiting step, while the Heyns rearrangement is fast. For instance, the imine formed from an amine of lens protein and the C-20 carbonyl of corticoids undergoes Heyns rearrangement, and the resulting Heyns product is involved in the cataract formation.

Under reducing conditions, such as in the presence of sodium cyanoborohydride NaBH3CN, the imine or Schiff base is reduced to secondary α-hydroxyamine, and no Heyns rearrangement occurs. Additionally, α-ketoamines can be destroyed by acidic hydrolysis, whereas α-hydroxyamines formed under reducing conditions are stable in acidic hydrolysis.

With α-hydroxy carbonyl scaffold, carbohydrates undergo two different reactions with proteins requiring no group protection manipulations. Aldoses give the Amadori products, existing only in the keto form with an α-hydroxy carbonyl function in the open chain form. In contrast, ketoses form several Heyns products, but mainly in the aldehyde form without the α-hydroxy carbonyl functionality (e.g., the conversion of lactoulose into different lactosamine derivatives). Both Amadori products and Heyns products can undergo further reactions, depending on the reactivity of the carbonyl group.

The Amadori products, bearing an α-hydroxy carbonyl group, more readily undergo the enolization, dehydration, elimination, cyclization, migration of carbonyl group, and retro-aldol reaction. For instance, the Heyns products brown slower than those of Amadori products at 110 °C under free access of oxygen.

All these transformations make up the Maillard reaction, leading to the formation of highly reactive compounds that may decompose into small volatile flavor compounds, polymerization into high molecular weight brown pigments known as mellanoidins, or the formation of fluorescent compounds widely applied in food, cosmetic, and pharmaceutical industries.

References

Heyns, K. and Koch, W., “Über die Bildung eines Aminozuckers aus d-Fructose und Ammoniak” [On the formation of an amino sugar from d-fructose and ammonia.] Zeitschrift für Naturforschung B 1952 7 486-488

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