Zincke reaction

The Zincke reaction is an organic reaction in which a pyridine is transformed into a pyridinium salt by reaction with 2,4-dinitro-chlorobenzene and a primary amine, named after Theodor Zincke. The Zincke reaction is an organic reaction in which a pyridine is transformed into a pyridinium salt by reaction with 2,4-dinitro-chlorobenzene and a primary amine, named after Theodor Zincke. The Zincke reaction should not be confused with the Zincke-Suhl reaction or the Zincke nitration. Furthermore, the Zincke reaction has nothing to do with the chemical element zinc. The first reaction is the formation of the N-2,4-dinitrophenyl-pyridinium salt (2). This salt is typically isolated and purified by recrystallization. Upon heating a primary amine with the N-2,4-dinitrophenyl-pyridinium salt (2), the addition of the amine leads to the opening of the pyridinium ring. A second addition of amine leads to the displacement of 2,4-dinitroaniline (5) and formation of the König salt (6a and 6b). The trans-cis-trans isomer of the König salt (6a) can react by either sigmatropic rearrangement or nucleophilic addition of a zwitterionic intermediate to give cyclized intermediate (7). This has been suggested to be the rate-determining step. After proton transfer and amine elimination, the desired pyridinium ion (9) is formed. This mechanism can be referred to as an instance of the ANRORC mechanism: nucleophilic addition (AN), ring opening and ring closing. In one solid-phase synthesis application, the amine is covalently attached to Wang resin. Another example is the synthesis of a chiral isoquinolinium salt. With secondary amines and not primary amines the Zincke reaction takes on a different shape forming so-called Zincke aldehydes in which the pyridine ring is ring-opened with the terminal iminium group hydrolyzed to an aldehyde: This variation has been applied in the synthesis of novel indoles: