Bohlmann-Rahtz Pyridine Synthesis is an efficient two-step method for obtaining substituted pyridines. In the first step, an enamine condenses with an alkynone to form an aminodiene intermediate. This is followed by a thermally induced E/Z isomerization, and then a cyclodehydration reaction occurs, forming a 2,3,6-trisubstituted pyridine. The reaction was first discovered in 1957 by Ferdinand Bohlmann and Dieter Rahtz, and is named after them.

Reagents: Solvent
Reactants: Enamine, alkynone
Product: 2,3,6-trisubstituted pyridine
Reaction type: Cyclization reaction

Experimental Tips:
For enamines that are difficult to synthesize, they can be generated in situ in the reaction system by adding ammonium acetate and directly used in the subsequent reaction.
The cyclodehydration process can be catalyzed by acetic acid, Amberlyst 15 ion-exchange resin, zinc bromide (II), or ytterbium triflate (III), effectively lowering the reaction temperature required for cyclization.

Reaction Mechanism

Original Reference:
Ferdinand Bohlmann, Dieter Rahtz. Chemische Berichte. 1957, 90 (10): 2265–2272.

Popular Citations:

• The Bohlmann-Rahtz Pyridine Synthesis: From Discovery to Applications. Synlett. 2007, 16, 2459–2482.

• One-Pot Multistep Bohlmann−Rahtz Heteroannulation Reactions: Synthesis of Dimethyl Sulfomycinamate. J. Org. Chem. 2005, 70(4), 1389–1399.

• Synthesis of tetrasubstituted pyridines by the acid-catalysed Bohlmann–Rahtz reaction. J. Chem. Soc., Perkin Trans. 1. 2002, 1663–1671.