Tropinone

Tropinone is an alkaloid, first synthesised in 1917 by Robert Robinson as a synthetic precursor to atropine, a scarce commodity during World War I. Tropinone and the alkaloids cocaine and atropine all share the same tropane core structure.

Synthesis
In organic chemistry the first laboratory preparation of tropinone is considered a milestone in total synthesis. Tropinone is a bicyclic molecule, but the reactants used in its preparation are fairly simple: succinaldehyde, methyl amine and acetone dicarboxylic acid (or even acetone). The synthesis is a good example of a biomimetic reaction or biogenetic-type synthesis because biosynthesis makes use of the same building blocks. It also demonstrates a tandem reaction in a one-pot synthesis.

Reaction mechanism
The main features apparent from the reaction sequence below are:


 * 1) Nucleophilic addition of secondary amine to aldehyde followed by loss of water to create an imine
 * 2) Nucleophilic addition of the imine to the second aldehyde unit and first ring closure
 * 3) Intermolecular Mannich reaction of the enolate of actone dicarboxylate
 * 4) New enolate formation and new imine formation with loss of water for
 * 5) Second intramolecular mannich reaction and second ring closure
 * 6) Loss of 2 carboxylic groups to tropinone