Strecker synthesis

What is Strecker synthesis?

The Strecker synthesis, which involves the formation of imines from aldehydes and ammonia or amines, followed by cyanation of the resulting imines using hydrogen cyanide or equivalents, and subsequent hydrolysis of the resulting α-amino nitriles, is considered the first multicomponent reaction (MCR) in organic chemistry. This reaction is also known as the Strecker amino acid synthesis, Strecker condensation, or Strecker hydrocyanation, but more commonly as the Strecker reaction or Strecker synthesis.

Strecker synthesis - general reaction scheme - Strecker amino acid synthesis - Strecker condensation - Strecker hydrocyanation - Strecker reaction
Strecker synthesis

= alkyl, aryl, vinyl, etc. (see list of acronyms)

The Bucherer-Bergs hydantoin synthesis and the Knoevenagel and Bucherer protocols are similar methods used for the de novo synthesis of α-amino acids. However, the Bucherer-Bergs hydantoin synthesis has advantages over the Strecker synthesis due to the irreversible formation of hydantoin and the makeup of the carbonyl group as an unreactive ketal before hydantoin, whereas the cyanation of imine in the Strecker synthesis is reversible.

The reversibility of the cyanation of imine is evidenced by the epimerization of the α-amino nitrile, prepared from benzaldehyde, (1S,2S)-1-amino-2-indanol, and TMSCN in DMSO at room temperature, to a 1:1 racemic mixture and to a single diastereomer in the solid state at 65 °C. The Bucherer-Bergs yydantoin synthesis is not feasible for the preparation of α-amino acids with a halogen adjacent to the chiral center.

References

  • Laurent, A. and Gerhardt, C. F., Ann. Chem. Phys., 1838, 66, 181
  • Laurent, A. and Gerhardt, C. F., Liebigs Ann. Chem., 1838, 28, 265
  • Strecker, A., Ann., 1850, 75, 27
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