Department of Organic Chemistry, Faculty of Chemistry, National Autonomous University of Mexico. Mexico City (CDMX), Mexico.
Received on 05 March 2026; revised on 15 April 2026; accepted on 18 April 2026
The morphine-apomorphine rearrangement starts by the acid promoted dehydration of the allylic alcohol at C-6, and double bond shift generates an allylic carbonium ion at C-8. This carbocation is the driving force for a 1,3-migration via opening of the bridged piperidine ring. Thus, the definitive D ring is formed. The tertiary, benzylic carbonium ion resulting from the migration is thermodynamically correct since a more stable carbonium ion is formed. Deprotonation gives a double bond conjugated with the benzene ring. Finally, protonation of the oxygen in the 1,2-dihydrofuran ring provokes ring opening at the alicyclic side. An allylic carbonium ion is generated whose neutralization forms the aromatic ring C.
However, there are in Internet other two sequences for apomorphine formation. The Kate tutorials start by breaking a cyclic ether, instead of dehydration of a much more reactive allylic alcohol. So, the route is wrong from the beginning and must be discarded. Besides, the following intermediates carry a very unstable primary carbonium ion. The other proposed sequence is due to Elsinghorst and start by dehydration of the allylic alcohol, but it misses the allylic carbonium ion at C-8, which is the driving force for a 1,3-migration that creates the new ring D. Then is opening of the dihydrofuran ring, a secondary carbonium ion is formed, and a thermodynamically forbidden step is proposed: formation of a primary carbonium ion. Thus, this route cannot be accepted-
Allylic alcohol; Dihydrofuran; Driving force; Primary carbonium ion; Thermodynamically forbidden
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F. Sánchez-Viesca and Luz Clarita. Theoretical study on apomorphine formation. Magna Scientia Advanced Research and Reviews, 2026, 16(02), 242-245. Article DOI: https://doi.org/10.30574/msarr.2026.16.2.0060