Guareschi-Thorpe pyridine synthesis

What is Guareschi-Thorpe pyridine synthesis?

The Guareschi-Thorpe pyridine synthesis, also referred as the Guareschi reaction, initially reported by Guareschi in 1896 and fully extended by Thorpe starting in 1911, involves the condensation of acetoacetic esters and cyanoacetic acids (or its esters and amides) in the presence of ammonia to produce pyridine derivatives.

Guareschi-Thorpe pyridine synthesis - Guareschi reaction - general reaction scheme
Guareschi-Thorpe pyridine synthesis

The resulting cyclic dicyano-imides are known as Guareschi products or Guareschi imides. While ketones can also condense with cyanoacetic esters or amides, this reaction is limited to methyl alkyl ketones only, including acetone, and does not work for ketones with carbonyl group adjacent to a ring junction. Malonic acid and its esters do not undergo this reaction.

The Guareschi-Thorpe pyridine synthesis has been utilized to prepare β-alkyl glutaric acid from aldehydes and cyanoacetamide.

References

Shares