Pictet–Spengler reaction

The Pictet–Spengler reaction is a chemical reaction in which a β-arylethylamine such as tryptamine undergoes ring closure after condensation with an aldehyde or ketone. Usually an acidic catalyst is employed and the reaction mixture heated, but some reactive compounds give good yields even at physiologic conditions. The Pictet–Spengler reaction can be considered a special case of the Mannich reaction.

The reaction was discovered in 1911 by Amé Pictet and Theodor Spengler. It has remained an important reaction in the fields of alkaloid and pharmaceutical synthesis. The Pictet–Spengler reaction product of tryptophan and aldoses can be identified in foodstuffs such as soy sauce and ketchup.

Nucleophilic aromatic rings such as indole or pyrrole give products with good yields and mild conditions, while less nucleophilic aromatic rings such as benzene give poor yields despite high temperatures and strong acid. The original Pictet–Spengler reaction was the reaction of β-phenethylamine with the dimethyl acetal of formaldehyde and hydrochloric acid forming a tetrahydroisoquinoline.