Epibatidine, isolated from tropical frogs, is about 200 times more effective as a pain reliefer than — Analytical Chemistry Chemistry Question
Epibatidine
Epibatidine, isolated from tropical frogs, is about 200 times more effective as a pain reliefer than morphine and is not addictive. In the synthesis towards epibatidine, A is converted to B by an intramolecular SN2 reaction.
[VISUAL]
precursor of epibatidine
Mark all asymmetric stereocenters in A by an *.
Model Answer
The four stereocenters of A are the four substituted carbon atoms on the cyclohexane ring (bearing the two -Br groups, the -NH2 group, and the -Ar group respectively). In the solution, these four positions are marked with asterisks (*).
Determine the absolute configuration of A according to the CIP (R/S) nomenclature at all stereocenters.
Model Answer
The absolute configurations at the stereocenters of A are:
- Carbon with -NH2: (R)
- Carbon with -Ar: (S)
- Carbon with -Br (adjacent to Ar-bearing carbon): (S)
- Carbon with -Br (adjacent to the other -Br): (S)
Draw a 3-D structure of A indicating from where the reaction to B takes place. Indicate the course of the reaction by an arrow between the reaction centres.
Model Answer
In a nucleophilic substitution (SN2), the nucleophile attacks the reaction centre at the back side with respect to the leaving group. In order to reach the reaction centre, the nucleophilic group (amino group) must take an axial position and subsequently replaces the bromine atom that points away from the incoming nucleophilic group. The 3-D drawing shows the cyclohexane ring of compound A in a chair conformation with the amino group in an axial position and an arrow pointing from the nitrogen lone pair to the back side of the carbon bearing the axial leaving bromide.
Draw a 3-D structure of B.
Model Answer
The 3-D structure of B is a bridged bicyclic amine (specifically a 7-azabicyclo[2.2.1]heptane derivative containing one bromine and one chloropyridyl substituent), representing the intramolecular cyclization product.