Bischler–Napieralski reaction

The Bishler -Napieralski reaction is a reaction in the field of organic chemistry, which is used to produce heterocycles. It is named after its discoverers, the chemists August Bishler and Bernard Napieralski named (formerly worked at the University of Zurich ) and describes the cyclization of amides in the presence of Lewis acids. This reaction is more commonly used in the total synthesis of alkaloids.

Reaction equation

Amides can be cyclized by the action of POCl 3 with elimination of water. However, this dehydration is purely formal, actually incurred in addition to the desired product HOPOCl2 and HCl.

Are the less nucleophilic aryl groups, drastic reaction conditions must be applied. Indoles react already are required for heating while higher temperatures in benzene. POCl3 is the most common drainage aids in chemical reactions. PCl5, polyphosphoric acid and ZnCl2 were also tested successfully.

Mechanism

For the mechanism of Bishler -Napieralski reaction, there are two different ways in the literature. Which takes place in the special case, depends on, inter alia, on the reaction conditions. The difference between the two options, at the time of elimination of the carbonyl oxygen atom. In mechanism I found it after the ring closure with formation of the imine in mechanism II they will form a nitrilium ion prior to ring closure instead.

Mechanism I:

Mechanism II:

Variant

Does the starting substance in α -position to the amino group, a hydroxy group, so enters a more formal elimination of water and it forms an isoquinoline derivative.

The Bishler -Napieralski reaction for the total synthesis of certain alkaloids (eg, papaverine, or reserpine) of signification.