tropinone+synthesis

James Mateka- The main parts of this tropinone synthesis are outlined below: a. Methylamine is added via nucleophilic addition to succinaldehyde. Once this is completed water is eliminated in order to create an imine. b. The imine is added to the intramolecular structure to the second aldehyde which in turn closes the first ring. c. Mannich Reaction takes place of the enolate of acetone dicarboxylate. d. A newly formed enolate and imine is caused by the loss of water e. The second ,mannich reaction takes place and the second ring now closes. f. 2 carboxylic groups are lost which creates tropinone. James Mateka

Addition to making atropine, one can also use this synthesis to yield tropic acid. This mechanism/synthesis is shown below: James Mateka This is a really good description of the double mannich reaction involved in the ring formation. Can you outline a synthesis other than atropine, using this reaction? Take a look at the paper on cocain that I put in the references. Bruce Bondurant



Is this last step a tautomerization to form the enolate? If that is the case, you would need to put in a double bond. What is used to reduce the double bond in the next step? Bruce Bondurant

You are right, in the first step there should have been a double bond between the carbon linked to the OH and the Carbon that is attached to the two oxygens and methyl group. I also missed a step in the second reaction, the 2-CMT should be reduced by Na(Hg) and H2SO4 to break the double bond before reacting with Pyridine and Benzoyl Chloride. Nadine Foxworth

This is an interesting synthesis. I think that the strategy of forming the mono methyl ester of the acetone decarboxylat, and the reduction that produces the exo alcoho are key to this synthesis. Can you comment briefly on the reaction steps and the strategy? With that, I think this project will be complete Bruce Bondurant

It actually looks like I missed a step. I n the first step there should have been a double bond between the carbon linked to the OH and the Carbon that is attached to the two oxygens and methyl group. I also missed a step in the second reaction, the 2-CMT should be reduced by Na(Hg) and H2SO4 to break the double bond before reacting with Pyridine and Benzoyl Chloride. The Benzoyl Chloride will loose the Cl and the OH on the reduced product will loose the H, allowing it to attach to the Benzyl and yeild Cocaine.

Sources: James Mateka 1. Wade 2.http://www.chm.bris.ac.uk/motm/atropine/synthesis.htm