Reissert reaction

What is Reissert reaction?

The synthesis of 1-benzoyl-2-cyano-1,2-dihydroquinoline was first reported in 1905 by Reissert, who prepared it by reacting quinoline, benzoyl chloride, and aqueous potassium cyanide.

Later, Grosheintz and Fischer extended this reaction to prepare acyl cyanodihydroquinoline from aliphatic acyl chloride with hydrogen cyanide and two equivalents of quinoline in dry benzene.

Reissert reaction - general reaction scheme - Reissert compound - Reissert-type reaction
Reissert reaction

R = alkyl, aryl, OEt, NMe2, etc. (see list of acronyms)

Similar compounds with structures analogous to Reissert’s dihydroquinoline were subsequently prepared from other types of heterocycles, including isoquinoline, benzimidazole, 1,6-naphthyridines, phenanthridine, pyrimidine, indazole, purine, quinazoline, quinoxaline, phthalazine, pyridazine, phenanthroline, pyrazine, and oxazole. These compounds, which are prepared similarly, are collectively referred to as Reissert compounds, and the method to prepare them is known as the Reissert reaction or Reissert-type reaction.

Reissert compounds can easily be converted into their conjugated bases through deprotonation, which has been widely used in organic synthesis. Due to the unsaturation of dihydroquinoline or dihydroisoquinoline moieties, Reissert compounds can undergo many reactions, including polymerization and cyclopropanation.

Additionally, Reissert compounds can undergo various reactions of particular interest. Upon acidic hydrolysis, Reissert compounds decompose to aldehyde (from the acyl moiety) and quinaldic acid, while treatment with PCl5 in chloroform leads to the decomposition of Reissert compounds to 2-cyanoquinoline and benzoyl chloride. They can also rearrange to C-acyl quinolines or isoquinolines when heated in strong base.

Moreover, the conjugate base of a Reissert compound can undergo alkylation with alkylating reagents, and the resulting alkylated Reissert compound decomposes to alkyl-substituted quinolines or isoquinolines when treated with base. These conjugate bases also condense with aldehydes to form secondary alcohols or their esters, of which the acyl groups migrate from nitrogen to oxygen in alkaline solution.

The condensation of Reissert compounds with Grignard reagents leads to the formation of carbinols, which rearrange to 2-acyl quinolines when treated with NaH. Cyclic urethanes can also be prepared from the conjugate bases of alkoxycarbonyl Reissert compounds with aromatic aldehydes.

It is worth noting that the decomposition of Reissert compounds to aldehyde under acidic conditions provides a route to convert acyl chloride into aldehyde. However, the preparation of Reissert compounds from aroyl and cinnamoyl chloride is unsuccessful in benzonitrile, ether, dioxane, acetone, or chloroform.