Tscherniak-Einhorn reaction

The Tscherniak-Einhorn reaction is an organic chemistry name reaction initiated in 1901 by Joseph Tscherniak. It involves the condensation of N- hydroxymethylphthalimide with varied aromatic compounds. This process was later expanded upon in 1905 by Alfred Einhorn to include the condensation of N- hydroxymethylchloroacetamide and benzoic or cinnamic acid.

Overview of reaction
This reaction entails an acid-catalyzed Electrophilic aromatic substitution amidoalkylation, utilizing an N-hydroxymethylamide or N-hydroxymethylimide, which are also known as the Tscherniak-Einhorn reagents. The reaction is catalyzed by potent acids such as 85-100% sulfuric acid, p-toluenesulfonic acid, methanesulfonic acid, or trifluoroacetic acid.



N-hydroxymethylamides may be prepared by the condensation of corresponding amides with an aqueous formaldehyde solution in dioxane, in the presence of sodium hydroxide.

Reaction mechanism
In the first step, the N-hydroxymethylamide is subject to acid protonation. Post water elimination, a mesomerically stabilized cation forms. This reacts with the aromatic compound in line with an electrophilic aromatic substitution process.



Applications
The Tscherniak-Einhorn reaction is used to synthesize some alkaloid derivatives.