Bischler-Napieralski Reaction
The Bischler-Napieralski reaction is an electrophilic aromatic substitution that allows the cyclization of beta-arylethylamides.
Bischler-Napieralski Reaction
Reaction Mechanism
1. The amide reacts with POCl3 to generate an iminium ion. 2. Cyclization via electrophilic aromatic substitution, SEAr. 3. Rearomatization of the benzene ring. And elimination. 2.2. Formation of a nitrilium ion. 3.2. Cyclization and rearomatization of the benzene ring.
Example
Experimental Procedure
To an oven dried RBF was added the substrate (0.29 mmol). Next, 2 mL of anhydrous DCM and 2 mL of POCl3 were added. The resulting solution was allowed to reflux for 4 hours. The reaction mixture was then cooled to room temperature and concentrated via rotary evaporation. The resulting residue was dissolved in a 9:1 mixture of MeOH:water, which was cooled to 0 ºC. NaBH4 was then added until pH 7. Next, 2 mL of saturated aq. NH4Cl solution was added dropwise, along with a small chunk of ice. The resulting mixture was diluted with 20 mL of DCM and transferred to a separatory funnel. The organic layer was removed, and the aqueous layer was extracted with DCM. The organic layers were combined, washed with brine, dried over MgSO4, filtered, and concentrated under vacuo. The crude solid was purified via column chromatography, and the solid obtained recrystallized from ethanol to obtain (–)-yohimbane.
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